WorldWideScience

Sample records for active visceral leishmaniasis

  1. Arginase activity in the blood of patients with visceral leishmaniasis and HIV infection.

    Yegnasew Takele

    Full Text Available BACKGROUND: Visceral leishmaniasis is a parasitic disease associated with high mortality. The most important foci of visceral leishmaniasis in Ethiopia are in the Northwest and are predominantly associated with high rates of HIV co-infection. Co-infection of visceral leishmaniasis patients with HIV results in higher mortality, treatment failure and relapse. We have previously shown that arginase, an enzyme associated with immunosuppression, was increased in patients with visceral leishmaniasis and in HIV seropositive patients; further our results showed that high arginase activity is a marker of disease severity. Here, we tested the hypothesis that increased arginase activities associated with visceral leishmaniasis and HIV infections synergize in patients co-infected with both pathogens. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a cohort of patients with visceral leishmaniasis and a cohort of patients with visceral leishmaniasis and HIV infection from Gondar, Northwest Ethiopia, and recorded and compared their clinical data. Further, we measured the levels of arginase activity in the blood of these patients and identified the phenotype of arginase-expressing cells. Our results show that CD4(+ T cell counts were significantly lower and the parasite load in the spleen was significantly higher in co-infected patients. Moreover, our results demonstrate that arginase activity was significantly higher in peripheral blood mononuclear cells and plasma of co-infected patients. Finally, we identified the cells-expressing arginase in the PBMCs as low-density granulocytes. CONCLUSION: Our results suggest that increased arginase might contribute to the poor disease outcome characteristic of patients with visceral leishmaniasis and HIV co-infection.

  2. Immunity and immunosuppression in experimental visceral leishmaniasis

    Goto H.

    2004-01-01

    Full Text Available Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4+ and CD8+ T cells, and interleukin (IL-2, interferon (IFN- gamma, and IL-12, the latter in a mechanism independent of IFN- gamma and linked to transforming growth factor (TGF-ß production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon re-infection, the elements involved in resistance are different, i.e., CD8+ T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-ß as well as apoptosis of CD4+ T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

  3. Epidemiology of visceral leishmaniasis

    Ready PD

    2014-05-01

    Full Text Available Paul D ReadyDisease Control Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UKAbstract: Leishmania species are the causative agents of leishmaniasis, a neglected tropical disease. These parasitic protozoans are usually transmitted between vertebrate hosts by the bite of blood sucking female phlebotomine sand flies. This review focuses on the two parasites causing most human visceral leishmaniasis (VL, which leads to substantial health problems or death for up to 400,000 people per year. Except for travel cases, Leishmania donovani infections are restricted to the (sub-tropics of Asia and Africa, where transmission is mostly anthroponotic, while Leishmania infantum occurs in the drier parts of Latin America as well as in the Mediterranean climate regions of the Old World, with the domestic dog serving as the main reservoir host. The prevalence of VL caused by L. infantum has been declining where living standards have improved. In contrast, infections of L. donovani continue to cause VL epidemics in rural areas on the Indian subcontinent and in East Africa. The current review compares and contrasts these continental differences and suggests priorities for basic and applied research that might improve VL control. Transmission cycles, pathogenesis, diagnosis, treatment and prognosis, prevention (including vector control, surveillance, transmission modeling, and international control efforts are all reviewed. Most case detection is passive, and so routine surveillance does not usually permit accurate assessments of any changes in the incidence of VL. Also, it is not usually possible to estimate the human inoculation rate of parasites by the sand fly vectors because of the limitations of survey methods. Consequently, transmission modeling rarely passes beyond the proof of principle stage, and yet it is required to help develop risk factor analysis for control programs. Anthroponotic VL

  4. Immunoactivation and immunopathogeny during active visceral leishmaniasis Imunoativação e imunopatogenia durante leishmaniose visceral ativa

    Hiro Goto

    2009-10-01

    Full Text Available Visceral leishmaniasis is caused by protozoan parasites of the Leishmania donovani complex. During active disease in humans, high levels of IFN-γ and TNF-α detected in blood serum, and high expression of IFN-γ mRNA in samples of the lymphoid organs suggest that the immune system is highly activated. However, studies using peripheral blood mononuclear cells have found immunosuppression specific to Leishmania antigens; this poor immune response probably results from Leishmania antigen-engaged lymphocytes being trapped in the lymphoid organs. To allow the parasites to multiply, deactivating cytokines IL-10 and TGF-β may be acting on macrophages as well as anti-Leishmania antibodies that opsonize amastigotes and induce IL-10 production in macrophages. These high activation and deactivation processes are likely to occur mainly in the spleen and liver and can be confirmed through the examination of organ samples. However, an analysis of sequential data from studies of visceral leishmaniasis in hamsters suggests that factors outside of the immune system are responsible for the early inactivation of inducible nitric oxide synthase, which occurs before the expression of deactivating cytokines. In active visceral leishmaniasis, the immune system actively participates in non-lymphoid organ lesioning. While current views only consider immunocomplex deposition, macrophages, T cells, cytokines, and immunoglobulins by diverse mechanism also play important roles in the pathogenesis.A leishmaniose visceral é causada por protozoários do gênero do complexo Leishmania donovani. Durante a doença ativa no homem são detectados altos níveis de IFN-γ e de TNF-α no soro, e elevada expressão de mRNA de IFN-γ em amostras de órgãos linfóides sugerindo um estado intensamente ativado do sistema imunológico. A visão atual, no entanto, refere-se à imunossupressão específica aos antígenos de Leishmania com base em estudos utilizando células mononucleares

  5. Treatment of visceral leishmaniasis

    E M Moore

    2010-01-01

    Full Text Available The available treatment options for visceral leishmaniasis (VL have problems relating to efficacy, adverse effects and cost, making treatment a complex issue. We review the evidence relating to the different methods of treatment in relation to - efficacy and toxicity of the drugs in different areas of the world; ability to monitor side effects, length of treatment; ability of patients to pay for and stay safe during treatment, ability of the healthcare services to give intramuscular, intravenous or oral therapy; the sex and child-bearing potential of the patient and the immune status of the patient. The high mortality of untreated/ poorly treated VL infection makes the decisions paramount, but a unified and coordinated response by each area is likely to be more effective and informative to future policies than an ad hoc response. For patients in resource-rich countries, liposomal amphotericin B appears to be the optimal treatment. In South Asia, miltefosine is being used; the combination of single dose liposomal amphotericin B and short course miltefosine looks encouraging but has the problem of potential reproductive toxicities in females. In Africa, the evidence to switch from SSG is not yet compelling. The need to monitor and plan for evolving drug failure, secondary to leishmania parasite resistance, is paramount. With a few drugs the options may be limited; however, we await key ongoing trials in both Africa and India to explore the effects of combination treatment. If safe and reliable combinations are revealed by the ongoing studies, it is far from clear as to whether this will avoid leishmania parasite resistance. The development of new drugs to add to the armamentarium is paramount. Lessons can be learnt from the management of diseases such as tuberculosis and malaria in terms of planning the switch to combination treatment. As important as establishing the best choice for specific antileishmanial agent is ensuring treatment centers

  6. Impact of ASHA training on active case detection of visceral leishmaniasis in Bihar, India.

    Vidya Nand Ravi Das

    2014-05-01

    Full Text Available BACKGROUND: One of the major challenges for management of visceral leishmaniasis (VL is early diagnosis of cases to improve treatment outcome and reduce transmission. We have therefore investigated active case detection of VL with the help of accredited social health activists (ASHA. ASHAs are women who live in the community and receive performance-based incentives for overseeing maternal and other health-related issues in their village. METHODS AND PRINCIPAL FINDING: Through conducting interviews with 400 randomly selected ASHAs from four primary health care centers (PHCs, it was observed that their level of knowledge about visceral leishmaniasis (VL regarding transmission, diagnosis, and treatment was limited. The baseline data indicated that less than 10% of VL cases seeking treatment at the PHCs were referred by ASHAs. To increase the knowledge and the referral rate of VL cases by ASHAs, training sessions were carried out during the monthly ASHA meetings at their respective PHCs. Following a single training session, the referral rate increased from less than 10% to over 27% and the overall knowledge about VL substantially improved. It was not possible, however, to demonstrate that ASHA training reduced the time that individuals had fever before treatment at the PHC. CONCLUSIONS: Training ASHAs to identify VL cases in villages for early diagnosis and treatment at the local PHC is feasible and should be undertaken routinely to improve knowledge about VL.

  7. Drug Combinations for Visceral Leishmaniasis

    Olliaro, P. L.

    2010-01-01

    PURPOSE OF REVIEW: Several attempts have been made to combine drugs for treating visceral leishmaniasis, but only recently have effective drugs become available and combinations been tested systematically. RECENT FINDINGS: Sequential treatments with liposomal amphotericin B followed by miltefosine or paromomycin (as short as 7 days), as well as the concomitant administration of miltefosine and paromomycin (for 10 days) are very effective in India (>95%). Sodium stibogluconate plus paromomycin...

  8. Arginase activity - a marker of disease status in patients with visceral leishmaniasis in ethiopia.

    Abebe, Tamrat; Takele, Yegnasew; Weldegebreal, Teklu; Cloke, Tom; Closs, Ellen; Corset, Camille; Hailu, Asrat; Hailu, Workagegnehu; Sisay, Yifru; Corware, Karina; Corset, Margaux; Modolell, Manuel; Munder, Markus; Tacchini-Cottier, Fabienne; Müller, Ingrid; Kropf, Pascale

    2013-01-01

    The underlying mechanisms resulting in the profound immune suppression characteristic of human visceral leishmaniasis (VL) are not fully understood. Here, we tested the hypothesis that arginase, an enzyme associated with immunosuppression, is higher in patients with VL and contributes to impaired T cell responses. We recruited patients with VL before and after treatment and healthy controls and measured the arginase metabolism in the blood of these individuals. Our results show that arginase activity is significantly higher in the blood of patients with active VL as compared to controls. These high levels of arginase decline considerably once the patients are successfully treated. We identified the phenotype of arginase-expressing cells among PBMCs as neutrophils and show that their frequency was increased in PBMCs of patients before treatment; this coincides with reduced levels of L-arginine in the plasma and decreased expression levels of CD3ζ in T cells. PMID:23556019

  9. Arginase activity - a marker of disease status in patients with visceral leishmaniasis in ethiopia.

    Tamrat Abebe

    Full Text Available The underlying mechanisms resulting in the profound immune suppression characteristic of human visceral leishmaniasis (VL are not fully understood. Here, we tested the hypothesis that arginase, an enzyme associated with immunosuppression, is higher in patients with VL and contributes to impaired T cell responses. We recruited patients with VL before and after treatment and healthy controls and measured the arginase metabolism in the blood of these individuals. Our results show that arginase activity is significantly higher in the blood of patients with active VL as compared to controls. These high levels of arginase decline considerably once the patients are successfully treated. We identified the phenotype of arginase-expressing cells among PBMCs as neutrophils and show that their frequency was increased in PBMCs of patients before treatment; this coincides with reduced levels of L-arginine in the plasma and decreased expression levels of CD3ζ in T cells.

  10. American visceral leishmaniasis in Chiapas, Mexico.

    Pastor-Santiago, Jorge A; Chávez-López, Susana; Guzmán-Bracho, Carmen; Flisser, Ana; Olivo-Díaz, Angélica

    2012-01-01

    We report the results of a study conducted during 1990-2006 with 89 cases of American visceral leishmaniasis in Chiapas State in southeastern Mexico and a seroprevalence study performed with 726 persons and 224 dogs that lived near cases of American visceral leishmaniasis. Clinical aspects, epidemiologic profiles, and risk factors are described. Most cases were in children ≤ 5 years of age, the prevalence of seropositive persons was 77%. The main risk factors associated with this disease were having 1-3 rooms in a house compared with ≥ 4 rooms, having a roof that was not made of cement, and having domestic animals. In contrast, only 19% of dogs were seropositive, suggesting that this species is not important in the transmission cycle of Leishmania. These data indicate that active transmission is taking place in the central valley of Chiapas State, Mexico, in communities located < 1,000 meters above sea level near the Grijalva River. PMID:22232459

  11. American Visceral Leishmaniasis in Chiapas, Mexico

    Pastor-Santiago, Jorge A.; Chávez-López, Susana; Guzmán-Bracho, Carmen; Flisser, Ana; Olivo-Díaz, Angélica

    2012-01-01

    We report the results of a study conducted during 1990–2006 with 89 cases of American visceral leishmaniasis in Chiapas State in southeastern Mexico and a seroprevalence study performed with 726 persons and 224 dogs that lived near cases of American visceral leishmaniasis. Clinical aspects, epidemiologic profiles, and risk factors are described. Most cases were in children ≤ 5 years of age, the prevalence of seropositive persons was 77%. The main risk factors associated with this disease were...

  12. Canine visceral leishmaniasis in Sicily.

    Orndorff, G R; Cooper, B A; Smith, W; Ryan, J R

    2000-01-01

    The Sicilian province of Catania is an active foci for human visceral leishmaniasis (VL) in the Mediterranean area. Approximately 10 to 15 cases of VL are diagnosed via hospital admissions each year in this community. Recently, an increase in VL case reporting by Sicilian physicians was noted, with 38 and 37 VL cases in 1996 and 1997, respectively. Before 1995, there were no reported VL cases among U.S. military personnel or their family members living in Sicily. However, since 1996, there have been four cases referred to Walter Reed Army Medical Center for diagnosis and treatment, all involving the children of personnel assigned to Naval Air Station Sigonella. Exposure histories for all infected individuals excluded exposure to Leishmania parasites outside of Sicily. All patients lived in areas where vectoring sandflies are present. All had dogs as family pets. To evaluate the level of infection among dogs owned by Navy personnel and their families, U.S. Navy Environmental and Preventive Medicine Unit 7, in a collaborative study with the U.S. Army Veterinary Clinic, Naval Air Station Sigonella, and the Walter Reed Army Institute of Research, performed clinical evaluation and serological testing of 50 dogs residing with U.S. personnel assigned to Naval Air Station Sigonella. The data indicate a high exposure rate to Leishmania (60% of the animals tested had elevated immunoglobulin M antibody levels) in the study population, suggesting that they were infected with Leishmania infantum. Distribution of seropositive dogs by sex was equal. Most of the dogs studied appeared to be in good health. However, inapparent infection of dogs, seen by Italian veterinarians, has been observed throughout all areas of Catania. Sandflies responsible for vectoring L. infantum were trapped in the same locations as the dogs sampled in this study. The level of subclinical infection was 75% among seropositive dogs. The overall level of canine infection observed was higher than expected

  13. Visceral Leishmaniasis In A Native Kashmiri Boy

    Deepti Mahajan, M.L. Bhat

    2009-07-01

    Full Text Available Leishmaniasis, though widely prevalent in South Asia, is not seen in the Kashmir valley where the coldclimatic conditions create a hostile environment for the growth of the parasite or its vector, the sandfly.However, a few cases of cutaneous leishmaniasis have been documented from the hot and arid Uri belt ofKashmir. We present a case of visceral leishmaniasis in a boy hailing from Uri, a rarity in this region.

  14. Visceral Leishmaniasis In A Native Kashmiri Boy

    Deepti Mahajan, M.L. Bhat; Singh, J B.; Deepa Hans

    2009-01-01

    Leishmaniasis, though widely prevalent in South Asia, is not seen in the Kashmir valley where the coldclimatic conditions create a hostile environment for the growth of the parasite or its vector, the sandfly.However, a few cases of cutaneous leishmaniasis have been documented from the hot and arid Uri belt ofKashmir. We present a case of visceral leishmaniasis in a boy hailing from Uri, a rarity in this region.

  15. Leishmanicidal activities of Artemisia annua leaf essential oil against Visceral Leishmaniasis.

    Islamuddin, Mohammad; Chouhan, Garima; Tyagi, Maujiram; Abdin, Malik Z; Sahal, Dinkar; Afrin, Farhat

    2014-01-01

    Visceral leishmaniasis (VL), the second-most dreaded parasitic disease after malaria, is currently endemic in 88 countries. Dramatic increases in the rates of infection, drug resistance, and non-availability of safe vaccines have highlighted the need for identification of novel and inexpensive anti-leishmanial agents from natural sources. In this study, we showed the leishmanicidal effect of essential oil from Artemisia annua leaves (AALEO) against Leishmania donovani in vitro and in vivo. AALEO was extracted by hydrodistillation and characterized by GC-MS, the most abundant compounds were found to be camphor (52.06 %) followed by β-caryophyllene (10.95 %). AALEO exhibited significant leishmanicidal activity against L. donovani, with 50 % inhibitory concentration of 14.63 ± 1.49 μg ml(-1) and 7.3 ± 1.85 μg ml(-1), respectively, against the promastigotes and intracellular amastigotes. The effect was mediated through programmed cell death as confirmed by externalization of phosphatidylserine, DNA nicking by TdT-mediated dUTP nick-end labeling assay, dyskinetoplastidy, cell cycle arrest at sub-G0-G1 phase, loss of mitochondrial membrane potential and reactive oxygen species generation in promastigotes and nitric oxide generation in ex vivo model. AALEO presented no cytotoxic effects against mammalian macrophages even at 200 μg ml(-1). Intra-peritoneal administration of AALEO (200 mg/ kg.b.w.) to infected BALB/c mice reduced the parasite burden by almost 90% in the liver and spleen with significant reduction in weight. There was no hepato- or nephro-toxicity as demonstrated by normal levels of serum enzymes. The promising antileishmanial activity shown by camphor-rich AALEO may provide a new lead in the treatment of VL. PMID:25505453

  16. Leishmanicidal activities of Artemisia annua leaf essential oil against Visceral Leishmaniasis

    Mohammad eIslamuddin

    2014-11-01

    Full Text Available Visceral leishmaniasis (VL, the second-most dreaded parasitic disease after malaria, is currently endemic in 88 countries. Dramatic increases in the rates of infection, drug resistance and non-availability of safe vaccines have highlighted the need for identification of novel and inexpensive anti-leishmanial agents from natural sources. In this study, we showed the leishmanicidal effect of essential oil from Artemisia annua leaves (AALEO against Leishmania donovani in vitro and in vivo. AALEO was extracted by hydrodistillation and characterized by GC-MS, the most abundant compounds were found to be camphor (52.06 % followed by β-caryophyllene (10.95 %. AALEO exhibited significant leishmanicidal activity against L. donovani, with 50 % inhibitory concentration of 14.63 ± 1.49 µg ml-1 and 7.3 ± 1.85 µg ml─1, respectively, against the promastigotes and intracellular amastigotes. The effect was mediated through programmed cell death as confirmed by externalization of phosphatidylserine, DNA nicking by TdT-mediated dUTP nick-end labelling (TUNEL assay, dyskinetoplastidy, cell cycle arrest at sub-G0–G1 phase, loss of mitochondrial membrane potential and reactive oxygen species (ROS generation in promastigotes and nitric oxide (NO generation in ex vivo model. AALEO presented no cytotoxic effects against mammalian macrophages even at 200 µg ml─1. Intra-peritoneal administration of AALEO (200 mg/ kg.b.w. to infected BALB/c mice reduced the parasite burden by almost 90 % in the liver and spleen with significant reduction in weight. There was no hepato- or nephro-toxicity as demonstrated by normal levels of serum enzymes. The promising antileishmanial activity shown by camphor-rich AALEO may provide a new lead in the treatment of VL.

  17. Monoclonal gammopathy associated with visceral leishmaniasis

    Vishal Sharma

    2010-06-01

    Full Text Available Monoclonal gammopathy can accompany diverse conditions and is usually benign. It should be distinguished from monoclonal gammopathy of undetermined significance (MGUS which can rarely turn malignant. Visceral leishmaniasis has only rarely been associated with monoclonal gammopathy. We describe the case of a 55-year-old male who had monoclonal gammopathy associated with visceral leishmanisais, which reversed with stibogluconate therapy.

  18. Oral mucosal involvement in visceral leishmaniasis

    Sunny Garg; Richik Tripathi; Kamlakar Tripathi

    2013-01-01

    Leishmaniasis affects both the visceral and cutaneous tissues in body.OralMucosal involvement in leishmaniasis is rare and is often overlooked.We present a case17 year old boy from the north east region ofBihar who has a history of visceral leishmaniasis one year back, came to the department of oral surgery for treatment of persistent oral ulcers.Oral examination did not give any diagnostic information while systemic examination revealed enlarged spleen and low grade fever.Patient was screened for leishmaniasis by rK39 based immunochromatographic strip test which came to be positive.Biopsy of the ulcer as well as splenic and bone marrow aspirate confirmed the presence of leishmaniasis.Patient was administeredAmphotericinB for20 days following which significant clinical and haematological improvement followed.

  19. Effectiveness and Feasibility of Active and Passive Case Detection in the Visceral Leishmaniasis Elimination Initiative in India, Bangladesh, and Nepal

    Hirve, Siddhivinayak; Singh, Shri Prakash; Kumar, Narendra; Banjara, Megha Raj; Das, Pradeep; Sundar, Shyam; Rijal, Suman; Joshi, Anand,; Kroeger, Axel; Varghese, Beena; Thakur, Chandreshwar Prasad; Huda, M Mamun; Mondal, Dinesh

    2010-01-01

    This study analyzed the effectiveness of active case detection (ACD) for new visceral leishmaniasis (VL) cases. ACD detection was carried out using house to house screening in Bangladesh and India and by neighborhood screening around index cases in Nepal. The percent increase of new VL cases through ACD compared to PCD was 6.7–17.1% in India; 38.8% in Nepal; and 60% in Bangladesh. The screening effort was high in India and Bangladesh (house to house screening) compared to Nepal (index case sc...

  20. Visceral leishmaniasis: a forgotten epidemic.

    Zijlstra, Eduard E

    2016-06-01

    Visceral leishmaniasis (VL or kala-azar) is most endemic in Asia and Africa and commonly affects young children. It is usually caused by Leishmania donovani or Leishmania infantum that are transmitted by Phlebotomine sand flies. Transmission may be anthroponotic or zoonotic or both, depending on the endemic area. Clinical features include fever, hepatosplenomegaly, weight loss and pancytopenia. Younger age, malnutrition and immunosuppression (HIV infection, use of immunosuppressive drugs) are risk factors. Many infections remain asymptomatic. Diagnosis is made by demonstration of the Leishmania parasite in aspirates of lymph node, bone marrow or spleen. Serological tests such as rK39 strip test are widely used but the sensitivity varies. qPCR is useful to detect low numbers of parasites and to monitor treatment. Treatment is with AmBisome monotherapy in most areas but with drug combinations elsewhere. HIV co-infected patients are most difficult to treat and often relapse. Control efforts focus on case finding, availability of diagnostic tools, reservoir control and protection from sand flies (insecticides, bed nets). There is no human vaccine. PMID:26895806

  1. Changing Pattern of Visceral Leishmaniasis, United Kingdom, 1985-2004

    Malik, Aeesha N J; John, Lawrence; Bryceson, Anthony D.M.; Lockwood, Diana N. J.

    2006-01-01

    A 20-year (1985–2004) retrospective review of 39 patients with imported visceral leishmaniasis found that tourism to Mediterranean countries and HIV infection were associated with visceral leishmaniasis. Diagnosis was often delayed. Treatment with liposomal amphotericin B has improved prognosis. Visceral leishmaniasis should be made a reportable disease.

  2. Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis.

    Meenakshi Sharma

    Full Text Available BACKGROUND: Most available drugs against visceral leishmaniasis are toxic, and growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine against visceral leishmaniasis deepens the crisis. Antineoplastic drugs like miltefosine have in the past been effective against the parasitic infections. An antineoplastic drug, cisplatin (cis-diamminedichloroplatinum II; CDDP, is recognized as a DNA-damaging drug which also induces alteration of cell-cycle in both promastigotes and amastigotes leading to cell death. First in vivo reports from our laboratory revealed the leishmanicidal potential of cisplatin. However, high doses of cisplatin produce impairment of kidney, which can be reduced by the administration of antioxidants. METHODOLOGY/PRINCIPAL FINDINGS: The present study was designed to evaluate the antileishmanial effect of cisplatin at higher doses (5 mg and 2.5 mg/kg body weight and its combination with different antioxidants (vitamin C, vitamin E and silibinin so as to eliminate the parasite completely and reduce the toxicity. In addition, various immunological, hematological and biochemical changes induced by it in uninfected and Leishmania donovani infected BALB/c mice were investigated. CONCLUSION/SIGNIFICANCE: A significant reduction in parasite load, higher IgG2a and lower IgG1 levels, enhanced DTH responses, and greater concentration of Th1 cytokines (IFN-γ, IL-2 with a concomitant down regulation of IL-10 and IL-4 pointed towards the generation of the protective Th1 type of immune response. A combination of cisplatin with antioxidants resulted in successful reduction of nephrotoxicity by normalizing the enzymatic levels of various liver and kidney function tests. Reduction in parasite load, increase in Th1 type of immune responses, and normalization of various biochemical parameters occurred in animals treated with cisplatin in combination with various antioxidants as

  3. [Visceral leishmaniasis: not only a tropical disease].

    Cuperus, F.J.C.; Oosterwijk, P.R.; Vos, A.; Remijn, J.A.; Dobbenburgh, A. van; Bisseling, T.M.

    2013-01-01

    We report 2 cases of visceral leishmaniasis in Dutch patients after a stay in Greece and the former Yugoslavia, respectively. Patient A, a 69-year-old woman, was referred to our department with abdominal pain. Additional examinations were suggestive of chronic liver disease. After a liver biopsy, wh

  4. Aetiology of visceral leishmaniasis in Mexico.

    Monroy-Ostria, A; Hernandez-Montes, O; Barker, D C

    2000-03-25

    Two children with visceral leishmaniasis (VL), were studied by DNA analysis. DNA from liver biopsy samples from both patients, was amplified by PCR with broad primers specific for the Leishmania subgenus. DNA from the patient from Chiapas was also amplified with primers specific for the Leismania donovani complex and hybridised with a probe specific for L. donovani complex. The second patient, who is the first reported case of visceral leishmaniasis in the Mexican state of Tabasco, where localised cutaneous leishmaniasis and DCL predominate, had a co-infection with Toxoplasma gondii. The DNA from this patient was not amplified with primers specific for the L. donovani complex, did not hybridise with a probe specific for the L. donovani complex, but did hybridise with kDNA from a Mexican Leishmania mexicana strain used as a probe. We therefore, suggest that members of the L. donovani or L. mexicana complexes cause VL in Mexico. PMID:10708655

  5. Leishmania-specific T cells expressing interferon-¿(IFN-¿) and IL-10 upon activation are expanded in individuals cured of visceral leishmaniasis

    Kemp, K; Kemp, M; Kharazmi, A;

    1999-01-01

    Peripheral blood mononuclear cells (PBMC) from patients who have recovered from visceral leishmaniasis often respond to Leishmania antigens in vitro by production of both IL-4, IFN-gamma and IL-10. In order to establish the cellular sources of these cytokines, we activated cells from individuals...... with a history of visceral leishmaniasis with Leishmania antigen for 6 days in culture, and identified cytokine production at the single-cell level by flow cytometry. The cytokines were only found in CD3+ cells and among these mainly within the CD4+ subset. The percentage of cytokine-producing cells was compared...... in Leishmania-activated PBMC cultures from the previous patients and from individuals living in a village where leishmaniasis does not occur. The percentage of IL-10- and IFN-gamma-containing cells was significantly higher in the previous patients than in the controls, indicating that Leishmania-specific T...

  6. Hemophagocytic Lymphohistiocytosis Associated with Visceral Leishmaniasis in Late Adulthood

    Cançado, Guilherme Grossi Lopes; Freitas, Guilherme Gomes; Faria, Flavia Helena Fidelis; Vaz de Macedo, Antonio; Nobre, Vandack

    2013-01-01

    We describe a case of hemophagocytic lymphohistiocytosis related to visceral leishmaniasis in late adulthood. Because clinical features of visceral leishmaniasis can mimic those of hemophagocytic lymphohistiocytosis, diagnosing leishmaniasis as the underlying etiology can be quite challenging. In our case, treatment with amphotericin B resulted in a dramatic resolution of clinical abnormalities.

  7. First report of canine visceral leishmaniasis in Bulgaria

    TSATCHEV, Illia; KYRIAZIS, Ioannis D.; BOUTSINI, Sofia; Karagouni, Evdokia; Dotsika, Eleni

    2010-01-01

    Seroepidemiological studies on canine leishmaniasis in Bulgaria, even in areas where human leishmaniasis has been detected, are controversial. This report describes 2 clinical cases of canine visceral leishmaniasis. The disease was confirmed by microscopical, serological, and molecular methods. It is, therefore, suggested that infected dogs could constitute the reservoir for human leishmaniasis in the country.

  8. Laboratory diagnosis of human visceral leishmaniasis

    Hercules Sakkas; Constantina Gartzonika; Stamatina Levidiotou

    2016-01-01

    Visceral leishmaniasis (VL), caused by the Leishmania donovani complex, is a vector-borne systemic disease, with a worldwide distribution causing high morbidity and mortality in the developing world. VL patients may be asymptomatic or they may present symptoms and findings of a systemic infection. The positive predictive value of clinical diagnosis in patients with typical symptoms is usually high, but more often, the signs and symptoms are inconclusive and mistaken with other co-endemic dise...

  9. Visceral leishmaniasis: Experimental models for drug discovery

    Gupta, Suman; Nishi

    2011-01-01

    Visceral leishmaniasis (VL) or kala-azar is a chronic protozoan infection in humans associated with significant global morbidity and mortality. The causative agent is a haemoflagellate protozoan Leishmania donovani, an obligate intracellular parasite that resides and multiplies within macrophages of the reticulo-endothelial system. Most of the existing anti-leishmanial drugs have serious side effects that limit their clinical application. As an alternate strategy, vaccination is also under ex...

  10. Regulation of PKC mediated signaling by calcium during visceral leishmaniasis.

    Roy, Nivedita; Chakraborty, Supriya; Paul Chowdhury, Bidisha; Banerjee, Sayantan; Halder, Kuntal; Majumder, Saikat; Majumdar, Subrata; Sen, Parimal C

    2014-01-01

    Calcium is an ubiquitous cellular signaling molecule that controls a variety of cellular processes and is strictly maintained in the cellular compartments by the coordination of various Ca2+ pumps and channels. Two such fundamental calcium pumps are plasma membrane calcium ATPase (PMCA) and Sarco/endoplasmic reticulum calcium ATPase (SERCA) which play a pivotal role in maintaining intracellular calcium homeostasis. This intracellular Ca2+ homeostasis is often disturbed by the protozoan parasite Leishmania donovani, the causative organism of visceral leishmaniasis. In the present study we have dileneated the involvement of PMCA4 and SERCA3 during leishmaniasis. We have observed that during leishmaniasis, intracellular Ca2+ concentration was up-regulated and was further controlled by both PMCA4 and SERCA3. Inhibition of these two Ca2+-ATPases resulted in decreased parasite burden within the host macrophages due to enhanced intracellular Ca2+. Contrastingly, on the other hand, activation of PMCA4 was found to enhance the parasite burden. Our findings also highlighted the importance of Ca2+ in the modulation of cytokine balance during leishmaniasis. These results thus cumulatively suggests that these two Ca2+-ATPases play prominent roles during visceral leishmaniasis. PMID:25329062

  11. Regulation of PKC mediated signaling by calcium during visceral leishmaniasis.

    Nivedita Roy

    Full Text Available Calcium is an ubiquitous cellular signaling molecule that controls a variety of cellular processes and is strictly maintained in the cellular compartments by the coordination of various Ca2+ pumps and channels. Two such fundamental calcium pumps are plasma membrane calcium ATPase (PMCA and Sarco/endoplasmic reticulum calcium ATPase (SERCA which play a pivotal role in maintaining intracellular calcium homeostasis. This intracellular Ca2+ homeostasis is often disturbed by the protozoan parasite Leishmania donovani, the causative organism of visceral leishmaniasis. In the present study we have dileneated the involvement of PMCA4 and SERCA3 during leishmaniasis. We have observed that during leishmaniasis, intracellular Ca2+ concentration was up-regulated and was further controlled by both PMCA4 and SERCA3. Inhibition of these two Ca2+-ATPases resulted in decreased parasite burden within the host macrophages due to enhanced intracellular Ca2+. Contrastingly, on the other hand, activation of PMCA4 was found to enhance the parasite burden. Our findings also highlighted the importance of Ca2+ in the modulation of cytokine balance during leishmaniasis. These results thus cumulatively suggests that these two Ca2+-ATPases play prominent roles during visceral leishmaniasis.

  12. American visceral Leishmaniasis: a case report

    H. Langoni

    2005-09-01

    Full Text Available Visceral leishmaniasis is a zoonotic disease caused by parasites of the Leishmania genus. Dog is the major source of infection to man, especially in urban areas. The authors report a case of visceral leishmaniasis in a pit bull female dog from Bocaina, São Paulo, Brazil. The animal presented clinical signs compatible with leishmaniasis, including skin lesions in the body and partial damage of the external ears. The indirect fluorescent antibody test (IFAT demonstrated a titer of 1280, and promastigote forms of Leishmania sp were isolated by the culture of bone marrow puncture. Cytological analysis of the lymph node and smear of the bone marrow puncture revealed macrophages containing amastigote forms of Leishmania sp in their inner region. The test of Polymerase Chain Reaction (PCR utilized the primers LINR4 and LIN19, which amplify 720 base pairs, specific for Leishmania sp. The authors discuss the importance of techniques for a quick and precise diagnosis to this serious zoonosis with great impact in animal and public health.

  13. Evidence that lipopolisaccharide may contribute to the cytokine storm and cellular activation in patients with visceral leishmaniasis.

    Joanna R Santos-Oliveira

    2011-07-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is characterized by parasite-specific immunosuppression besides an intense pro-inflammatory response. Lipopolisaccharide (LPS has been implicated in the immune activation of T-cell deficient diseases such as HIV/AIDS and idiopathic lymphocytopenia. The source of LPS is gram-negative bacteria that enter the circulation because of immunological mucosal barrier breakdown. As gut parasitization also occurs in VL, it was hypothesized that LPS may be elevated in leishmaniasis, contributing to cell activation. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry analysis and immunoassays (ELISA and luminex micro-beads system were used to quantify T-cells and soluble factors. Higher LPS and soluble CD14 levels were observed in active VL in comparison to healthy subjects, indicating that LPS was bioactive; there was a positive correlation between these molecules (r = 0.61;p<0.05. Interestingly, LPS was negatively correlated with CD4(+ (r = -0.71;p<0.01 and CD8(+ T-cells (r = -0.65;p<0.05. Moreover, higher levels of activation-associated molecules (HLA-DR, CD38, CD25 were seen on T lymphocytes, which were positively associated with LPS levels. Pro-inflammatory cytokines and macrophage migration inhibitory factor (MIF were also augmented in VL patients. Consistent with the higher immune activation status, LPS levels were positively correlated with the inflammatory cytokines IL-6 (r = 0.63;p<0.05, IL-8 (r = 0.89;p<0.05, and MIF (r = 0.64;p<0.05. Also, higher plasma intestinal fatty acid binding protein (IFABP levels were observed in VL patients, which correlated with LPS levels (r = 0.57;p<0.05. CONCLUSIONS/SIGNIFICANCE: Elevated levels of LPS in VL, in correlation with T-cell activation and elevated pro-inflammatory cytokines and MIF indicate that this bacterial product may contribute to the impairment in immune effector function. The cytokine storm and chronic immune hyperactivation status may

  14. Genetically Modified Organisms and Visceral Leishmaniasis

    NAHID eALI

    2014-05-01

    Full Text Available Vaccination is the most effective method of preventing infectious diseases. Since the eradication of small pox in 1976, many other potentially life compromising if not threatening diseases have been dealt with subsequently. This event was a major leap not only in the scientific world already burdened with many diseases but also in the mindset of the common man who became more receptive to novel treatment options. Among the many protozoan diseases, the leishmaniases have emerged as one of the largest parasite killers of the world, second only to malaria. There are three types of leishmaniases namely cutaneous (CL, mucocutaneous (ML and visceral (VL, caused by a group of more than 20 species of Leishmania parasites. Visceral leishmaniasis, also known as kala-azar is the most severe form and almost fatal if untreated. Since the first attempts at leishmanization, we have killed parasite vaccines, subunit protein or DNA vaccines, and now we have live recombinant carrier vaccines and live attenuated parasite vaccines under various stages of development. Although some research has shown promising results, many more potential genes need to be evaluated as live attenuated vaccine candidates. This mini-review attempts to summarize the success and failures of genetically modified organisms used in vaccination against some of major parasitic diseases for their application in leishmaniasis.

  15. Laboratory diagnosis of human visceral leishmaniasis

    Hercules Sakkas

    2016-01-01

    Full Text Available Visceral leishmaniasis (VL, caused by the Leishmania donovani complex, is a vector-borne systemic disease, with a worldwide distribution causing high morbidity and mortality in the developing world. VL patients may be asymptomatic or they may present symptoms and findings of a systemic infection. The positive predictive value of clinical diagnosis in patients with typical symptoms is usually high, but more often, the signs and symptoms are inconclusive and mistaken with other co-endemic diseases. The fact that HIV co-infections often produce atypical presentations and the heterogeneity of Leishmania species, which is common in many endemic regions, also complicate the diagnosis. Despite that, some of the parasitological methods are still considered to be the reference standard for VL diagnosis due to their specificity. The development of serological and molecular tests has further enhanced the diagnostic approach of VL. Recombinant antigens have improved the performance of serodiagnostic tests, with DAT and the rK39 antigen based immunochromatographic test being the most appropriate methods for the serological diagnosis of VL. Molecular techniques, despite the fact that their implementation is often difficult and infeasible, have become increasingly relevant due to remarkable sensitivity and specificity, and to the variability of tested samples. Quantitative polymerase chain reaction (qPCR has been shown to be superior than conventional PCR for the differentiation between active VL and asymptomatic infections, such as for the detection of VL-HIV coinfection. This review summarizes the available methods with their applications in the diagnosis of VL, and focuses on the recent developments in VL diagnostics.

  16. Laboratory diagnosis of human visceral leishmaniasis.

    Sakkas, Hercules; Gartzonika, Constantina; Levidiotou, Stamatina

    2016-01-01

    Visceral leishmaniasis (VL), caused by the Leishmania donovani complex, is a vector-borne systemic disease, with a worldwide distribution causing high morbidity and mortality in the developing world. VL patients may be asymptomatic or they may present symptoms and findings of a systemic infection. The positive predictive value of clinical diagnosis in patients with typical symptoms is usually high, but more often, the signs and symptoms are inconclusive and mistaken with other co-endemic diseases. The fact that HIV co-infections often produce atypical presentations and the heterogeneity of Leishmania species, which is common in many endemic regions, also complicate the diagnosis. Despite that, some of the parasitological methods are still considered to be the reference standard for VL diagnosis due to their specificity. The development of serological and molecular tests has further enhanced the diagnostic approach of VL. Recombinant antigens have improved the performance of serodiagnostic tests, with DAT and the rK39 antigen based immunochromatographic test being the most appropriate methods for the serological diagnosis of VL. Molecular techniques, despite the fact that their implementation is often difficult and infeasible, have become increasingly relevant due to remarkable sensitivity and specificity, and to the variability of tested samples. Quantitative polymerase chain reaction (qPCR) has been shown to be superior than conventional PCR for the differentiation between active VL and asymptomatic infections, such as for the detection of VL-HIV coinfection. This review summarizes the available methods with their applications in the diagnosis of VL, and focuses on the recent developments in VL diagnostics. PMID:27004573

  17. Visceral leishmaniasis diagnosed in a patient with MALT lymphoma

    Kaae, Jeanette; Nørgaard, Peter; Himmelstrup, B

    2007-01-01

    We report a case of visceral leishmaniasis in a 66-year-old female with a history of MALT lymphoma in the gastrointestinal tract. The patient presented with major hemorrhage per rectum and perforation of the small intestine. Due to unexplained decreasing platelets, lymphoma bone marrow involvement...... was suspected and bone marrow examination was performed. Surprisingly, Leishman-Donovan bodies were detected. The low platelet count, caused by the combination of MALT lymphoma and visceral leishmaniasis, appears to have aggravated the symptoms of the intestinal lymphoma. Leishmaniasis should be...... suspected even among asymptomatic patients with immune compromising illnesses and a travel history to areas where leishmaniasis is endemic....

  18. Liver transplant recipient with concomitant cutaneous and visceral leishmaniasis.

    Ozcan, Deren; Seçkin, Deniz; Allahverdiyev, Adil M; Weina, Peter J; Aydin, Hakan; Ozçay, Figen; Haberal, Mehmet

    2007-03-01

    Diagnosis of leishmaniasis in immunosuppressed patients may be a serious challenge for physicians because of the major clinical and laboratory differences with immunocompetent patients. In immunosuppressed patients, the disease is characterized usually by disseminated visceral involvement, atypical cutaneous lesions and persistent negativity of diagnostic tests. Here, we report an eight-yr-old liver transplant recipient with concomitant cutaneous and visceral leishmaniasis in whom the cutaneous lesion led to the diagnosis of systemic involvement. PMID:17300508

  19. Causes of pediatric visceral leishmaniasis in southeastern iran.

    Ali Hosseininasab; Iraj Sharifi; Mohammad Hossein Daei; Mehdi Zarean; Mahsa Dadkhah

    2014-01-01

    Leishmania infantum is the most frequent cause of visceral leishmaniasis and L. tropica has been rarely linked to the disease in Iran. In this study, bone marrow aspirates were collected from 10 child patients, suspected with visceral leishmaniasis referred to the Pediatric Wards of Kerman Medical Hospitals, Kerman, Iran during 2002–2011. Leishmania species were identified by using nested PCR in all slides. The PCR samples from nine patients indicated L. infantum as principal causative agent ...

  20. Presentation of AIDS with Disseminated Cutaneous and Visceral Leishmaniasis in Iran

    Mohammadali Davarpanah; Masumeh Rassaei; Fatemeh Sari aslani

    2015-01-01

    Leishmaniasis is an infectious disease in form of visceral (VL), cutaneous (CL), and mucocutaneous (MCL) leishmaniasis. Immunocompromised patients have increased risk of Leishmania infection, especially in endemic areas for visceral leishmaniasis, where in the world HIV/VL coinfection has become endemic. The case here suffers from both AIDS and visceral-cutaneous leishmaniasis. We report an Iranian woman with disseminated cutaneous and visceral leishmaniasis who became positive for HIV test.

  1. Lutzomyia longipalpis in Clorinda, Formosa province, an area of potential visceral leishmaniasis transmission in Argentina

    Oscar D Salomón

    2005-08-01

    Full Text Available Phlebotomine captures were performed during 2004 in Clorinda, Argentina. Clorinda is located across the branches of the Paraguay river in front of Asunción city, Paraguay. Reports of canine and human visceral leishmaniasis in Asunción have been increasing since 1997, however neither leishmaniasis cases nor sand flies were ever recorded from Clorinda. Light traps were located in migration paths (bridges, port, and peridomestic environments of Clorinda and surrounding localities. Lutzomyia longipalpis was found in Clorinda and Puerto Pilcomayo, first report in a potential visceral leishmaniasis transmission area for Argentina. Active surveillance is required immediately in the localities involved and the surrounding area.

  2. Cellular and humoral responses to Leishmania major virulence factors in healed cutaneous leishmaniasis and Mediterranean visceral leishmaniasis patients.

    Lakhal-Naouar, Inès; Boussoffara, Thouraya; Meddeb-Garnaoui, Amel; Ben Achour-Chenik, Yosser; Louzir, Hechmi; Chenik, Mehdi

    2009-01-01

    Cellular and humoral immune responses of healed cutaneous leishmaniasis and Mediterranean visceral leishmaniasis patients were evaluated against results for Leishmania major virulence proteins L. major protein disulfide isomerase (LmPDI) and mitogen-activated protein kinase kinase (MAPKK). Only MAPKK induces significant peripheral blood mononuclear cell proliferation with gamma interferon production as well as antibody responses. Thus, MAPKK may be of interest in Leishmania vaccination and se...

  3. Visceral leishmaniasis: experimental models for drug discovery.

    Gupta, Suman

    2011-01-01

    Visceral leishmaniasis (VL) or kala-azar is a chronic protozoan infection in humans associated with significant global morbidity and mortality. The causative agent is a haemoflagellate protozoan Leishmania donovani, an obligate intracellular parasite that resides and multiplies within macrophages of the reticulo-endothelial system. Most of the existing anti-leishmanial drugs have serious side effects that limit their clinical application. As an alternate strategy, vaccination is also under experimental and clinical trials. The in vitro evaluation designed to facilitate rapid testing of a large number of drugs has been focussed on the promastigotes milt little attention on the clinically relevant parasite stage, amastigotes. Screening designed to closely reflect the situation in vivo is currently time consuming, laborious, and expensive, since it requires intracellular amastigotes and animal model. The ability to select transgenic Leishmania expressing reporter proteins, such as the green fluorescent proteins (GFP) or the luciferase opened up new possibilities for the development of drug screening models. Many experimental animal models like rodents, dogs and monkeys have been developed, each with specific features, but none accurately reproduces what happens in humans. Available in vitro and in vivo methodologies for antileishmanial drug screening and their respective advantages and disadvantages are reviewed. PMID:21321417

  4. Human visceral leishmaniasis: a picture from Italy.

    Abdalmaula, Giuma Harun; Barbadoro, Pamela; Marigliano, Anna; Illuminati, Diego; Di Stanislao, Francesco; D'Errico, Marcello Mario; Prospero, Emilia

    2013-12-01

    The aim of our study was to describe the distribution of Visceral Leishmaniasis (VL) in Italy, focusing on HIV-infected patients, to estimate the burden of the disease and the public health actions that should be undertaken. A review of official notifications and hospitalization data has been performed. From 2006 to 2008, a total of 289 cases of VL were notified; the overall notification rate was 1.63/1,000,000 (95% CI 1.45-1.83). In total, 1192 VL-associated hospitalizations were detected, with a hospitalization rate of 6.71/1,000,000 (95% CI 6.34-7.10). For the age group "≤ 24 years", a statistically significant increase was detected (p<0.05). A total of 68.9% (n = 821) of hospitalizations were detected in HIV-positive patients. The geographic distribution of rates revealed a significant increase in the north-eastern area of the country. Our study confirms that the epidemiological pattern of VL is changing and that, in Italy, control measures and preventive strategies should be based on not only the official notification system but also hospital data. This would lead to the identification of areas of parasite spread and to the creation of awareness campaigns geared toward general practitioners in the affected areas. Easy case detection would allow for timely public health actions and strategies for the implementation of more effective interventions for reservoir control. PMID:23999330

  5. [Visceral leishmaniasis in Central Asia and Kazakhstan].

    Dergacheva, T I; Darchenkova, N N

    1990-01-01

    At present sporadic foci of visceral leishmaniasis (VL) are encountered mainly in the natural foci. The natural foci of VL are situated mainly in valleys and foothills. In southern areas of the Turkmen SSR the majority of cases were registered in small settlements situated near wells in interbarkhan lowerings. The reservoir of pathogen here may be Vulpes vulpes and dogs and the most likely vector is Phlebotomus turanicus. In Kazakhstan cases of VL are encountered in the thickets of the Syr-Darya floodlands in Kzyl-Orda Province, where the natural reservoir of the pathogen are Canis aureus L. and Vulpes corsac, and the vector is P. smirnovi. Synanthropic foci in Dzhambul and Chimkent, where dogs were most likely the source of the infection and P. longiductus was the vector, are at present inactive. The maps have been plotted where landscape dissemination of mosquitoes (VL vectors) is compared to places of habitation of Canis aureus L. and VL incidence in humans at peaks of the disease endemia. Medical personnel should be on the look-out for VL on the whole territory with VL natural foci. PMID:2146471

  6. Post-kala-azar Dermal Leishmaniasis Developing in Miltefosine-Treated Visceral Leishmaniasis

    Sankha Koley; Rajesh Kumar Mandal; Sanjiv Choudhary; Arghya Bandyopadhyay

    2013-01-01

    Post-kala-azar dermal leishmaniasis (PKDL) is an unusual dermatosis occurring following an attack of visceral leishmaniasis (VL). There are only few reports of PKDL after successful treatment with miltefosine. We report two cases of PKDL that developed after successful treatment of VL with miltefosine.

  7. Measures to Control Phlebotomus argentipes and Visceral Leishmaniasis in India

    Bublitz, DeAnna C.; Poché, Richard M.; Garlapati, Rajesh

    2016-01-01

    Visceral leishmaniasis is a deadly parasitic disease that is transmitted via the bite of a female sand fly, Phlebotomus argentipes. The highest burden of this disease is in northern India. In 2005, India embarked on an initiative with Nepal, Bangladesh, and the World Health Organization to eliminate visceral leishmaniasis by 2015. With the goal of 1 case in 10,000 people still unmet, it is prudent to evaluate the tools that have been used thus far to reduce vector numbers and cases of the disease. Herein, we present a review of studies conducted on vector-control strategies in India to combat visceral leishmaniasis including indoor residual spraying, insecticide-treated bed nets, environmental modification, and feed-through insecticides. This review suggests that the quality of indoor residual spraying may enhance control measures while a combination of spraying, nets, and feed-through insecticides would best confront the diverse habitats of P. argentipes. PMID:27308270

  8. Tuberous sclerosis with visceral leishmaniasis: a case report

    Pandey Krishna

    2009-09-01

    Full Text Available Abstract Introduction Visceral leishmaniasis, a tropical infectious disease, is a major public health problem in India. Tuberous sclerosis, a congenital neuro-ectodermosis, is an uncommon disease which requires life long treatment. Case presentation A 15-year-old Indian patient, presented to the outpatient department of our institute with a high-grade fever for two months, splenomegaly and a history of generalized tonic-clonic convulsions since childhood. The clinical and laboratory findings suggested visceral leishmaniasis with tuberous sclerosis. The patient was treated with miltefosine and antiepileptics. Conclusion The patient responded well and in a follow up six months after presentation, she was found free of visceral leishmaniasis and seizures. Diagnosis and treatment of this rare combination of diseases is difficult.

  9. First Case of Visceral Leishmaniasis Caused by Leishmania martiniquensis

    Liautaud, Bernard; Vignier, Nicolas; Miossec, Charline; Plumelle, Yves; Kone, Moumini; Delta, Delphine; Ravel, Christophe; Cabié, André; Desbois, Nicole

    2015-01-01

    We report the first case of visceral leishmaniasis (VL) caused by Leishmania martiniquensis in the Caribbean, which until now, was known only to cause cutaneous leishmaniasis. The disease presented with fatigue, anemia, and hepatosplenomegaly in a 61-year-old man with human immunodeficiency virus (HIV) infection who was receiving antiretroviral therapy. Diagnosis was made by bone marrow biopsy. VL is life-threatening, and its emergence in the Caribbean is of concern.

  10. First case of visceral leishmaniasis caused by Leishmania martiniquensis.

    Liautaud, Bernard; Vignier, Nicolas; Miossec, Charline; Plumelle, Yves; Kone, Moumini; Delta, Delphine; Ravel, Christophe; Cabié, André; Desbois, Nicole

    2015-02-01

    We report the first case of visceral leishmaniasis (VL) caused by Leishmania martiniquensis in the Caribbean, which until now, was known only to cause cutaneous leishmaniasis. The disease presented with fatigue, anemia, and hepatosplenomegaly in a 61-year-old man with human immunodeficiency virus (HIV) infection who was receiving antiretroviral therapy. Diagnosis was made by bone marrow biopsy. VL is life-threatening, and its emergence in the Caribbean is of concern. PMID:25404076

  11. Interest in paromomycin for the treatment of visceral leishmaniasis (kala-azar

    Wiwanitkit V

    2012-06-01

    Full Text Available Viroj Wiwanitkit1–31Wiwanitkit House, Bang Khae, Bangkok, Thailand; 2Hainan Medical University, Haikou, Hainan, People's Republic of China; 3Joseph Ayo Babalola University, Ikeji-Arakeji, Osun State, NigeriaAbstract: Leishmaniasis is an important vector-borne disease, and it is classified as one of the most important tropical fly-borne infections. This disease can cause two types of clinical manifestations: cutaneous forms and visceral forms. Visceral leishmaniasis, which is also called kala-azar, is a very serious infection that can be fatal. The management of visceral leishmaniasis requires informed diagnostic and therapeutic approaches. Continuous research and development regarding the treatment of visceral leishmaniasis had led to many improvements. Paromomycin is a relatively new antibiotic drug that has been used for the treatment of visceral leishmaniasis for several years. This article reviews and discusses the use of paromomycin for visceral leishmaniasis therapy.Keywords: visceral, leishmaniasis, paromomycin

  12. An effective in vitro and in vivo antileishmanial activity and mechanism of action of 8-hydroxyquinoline against Leishmania species causing visceral and tegumentary leishmaniasis.

    Costa Duarte, Mariana; Dos Reis Lage, Letícia Martins; Lage, Daniela Pagliara; Mesquita, Juliana Tonini; Salles, Beatriz Cristina Silveira; Lavorato, Stefânia Neiva; Menezes-Souza, Daniel; Roatt, Bruno Mendes; Alves, Ricardo José; Tavares, Carlos Alberto Pereira; Tempone, André Gustavo; Coelho, Eduardo Antonio Ferraz

    2016-02-15

    The development of new therapeutic strategies to treat leishmaniasis has become a priority. In the present study, the antileishmanial activity of 8-hydroxyquinoline (8-HQN) was investigated against in vitro promastigotes and in vivo intra-macrophage amastigotes of three Leishmania species: Leishmania amazonensis, Leishmania infantum and Leishmania braziliensis. Studies were performed to establish the 50% Leishmania inhibitory concentration (IC50) of 8-HQN, as well as its 50% cytotoxic concentration (CC50) on murine macrophages and in human red blood cells. The inhibition of macrophages infection was also evaluated using parasites that were pre-treated with 8-HQN. The effects of this compound on nitric oxide (NO) production and in the mitochondrial membrane potential were also evaluated. Finally, the therapeutic efficacy of 8-HQN was assessed in a known murine model, L. amazonensis-chronically infected BALB/c mice. Our results showed that 8-HQN was effective against promastigote and amastigote stages of all tested Leishmania species, presenting a selectivity index of 328.0, 62.0 and 47.0 for L. amazonensis, L. infantum and L. braziliensis, respectively. It was effective in treating infected macrophages, as well as in preventing the infection of these cells using pre-treated parasites. In addition, 8-HQN caused an alteration in the mitochondrial membrane potential of the parasites. When administered at 10mg/kg body weight/day by subcutaneous route, this product was effective in reducing the lesion diameter, as well as the parasite load in evaluated tissues and organs of infected animals. The results showed the in vitro and in vivo efficacy of 8-HQN against three different Leishmania species causing tegumentary and/or visceral leishmaniasis, and it could well be used for future therapeutic optimization studies to treat leishmaniasis. PMID:26827866

  13. Visceral leishmaniasis in a renal transplant recipient treated with allopurinol

    Harzallah Kais

    2010-01-01

    Full Text Available Leishmaniasis is an infection caused by a protozoan parasite belonging to the genus Leishmania and transmitted by the Phlebotomus sandfly. We report a case of visceral leishmaniasis in a 49-year-old male renal transplant recipient, a resident of the western part of Tunisia, which is an endemic zone for the disease. Just before and after the transplantation, the patient resided in Tunis, which is non-endemic for leishmaniasis. Visceral leishmaniasis occurred eight years after renal transplantation, and the clinical picture was characterized by fever and pancytopenia. Leish-maniae were detected by bone marrow aspiration. Pentavalent antimonal was used for 28 days and was substituted by allopurinol (20 mg/kg per day. One year after the infection, the patient remains totally asymptomatic. Our report suggests that visceral leishmaniasis may complicate the clinical course of organ transplantation and can be fatal, particularly when untreated. Relapses may occur after completion of the apparently effective treatment. Allopurinol could be a solution to avoid these relapses.

  14. Antimony to Cure Visceral Leishmaniasis Unresponsive to Liposomal Amphotericin B

    Morizot, Gloria; Jouffroy, Romain; Faye, Albert; Chabert, Paul; Belhouari, Katia; Calin, Ruxandra; Charlier, Caroline; Miailhes, Patrick; Siriez, Jean-Yves; Mouri, Oussama; Yera, Hélène; Gilquin, Jacques; Tubiana, Roland; Lanternier, Fanny; Mamzer, Marie-France; Legendre, Christophe; Peyramond, Dominique; Caumes, Eric; Lortholary, Olivier; Buffet, Pierre

    2016-01-01

    We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure. PMID:26735920

  15. Maiden Visit of Visceral Leishmaniasis to Malwa Region

    Shirish S Nandedkar, Kamal Malukani, Amit Varma

    2013-01-01

    Full Text Available Visceral Leishmaniasis is a well known public health problem in eastern parts of India. So far the cases have not been reported from Malwa plateu of Madhya Pradesh, to the best of our knowledge and available literature. We report here two cases of Visceral Leishmaniasis first time from the Malwa region. Both the cases are from the migratory population of Bihar. The diseases like Leishmaniasis which were previously restricted to endemic areas of the country are spreading to non endemic areas along with the large migratory population, which is seen with the development of the country.. The cases are reported to inform the National health authorities to take proper steps to curb the spread of the disease to non -endemic areas and to emphasize the need of vector surveys in these areas.

  16. Current treatment of visceral leishmaniasis (Kala-azar: an overview

    Premshanker S. Singh

    2014-06-01

    Full Text Available Visceral Leishmaniasis (VL is also popularly known as kala-azar which was first reported in early forties and since then it continues to affect millions of people. The ranges of common drugs available for the treatment of visceral leishmaniasis are limited. It mainly includes pentavalent antimonials e.g. stibogluconate (SbV, amphotericin B deoxycholate (AB, lipid formulations of amphotericin B (L-AB, miltefosine (MF and paromomycin (PM - all of which have limitations in terms of toxicity, variable efficacy, price and inconvenient treatment schedules. Most are parenteral except MF which is administered orally. Due to the parasite and #8217;s drug resistance, the most widely used (SbV of these drugs is now of little use in northern Bihar, India, which alone accounts for 50% of the worlds burden of visceral leishmaniasis. In areas of resistance to SbV, AB is highly effective. The formulation of AB in liposomes (L-AB has been a major advancement in the treatment of visceral leishmaniasis. However, despite a significant reduction in price, this treatment remains very expensive for endemic countries like India. Combination short course therapy has been reported by many researchers who found that it is equally effective as conventional monotherapy with added benefits of less side effects, better compliance and less resistance. The aim of this article is to review the current aspects of the treatment for leishmaniasis, giving an overview of current agents clinically used to new agents and modalities of treatment under development. [Int J Res Med Sci 2014; 2(3.000: 810-817

  17. Trace elements in sera from patients with visceral leishmaniasis

    Trace elements are known to have pivotal role in human health and disease. Present investigation employed PIXE analysis to probe into the elemental profile of patients suffering from visceral Leishmaniasis. Remarkable alternations were observed in concentration of elements like Cl, K, Ca, Mn, Fe, Cu, Zn. The pattern of enhancement of elemental concentration corresponds to the progression of the disease. Additionally, our present data reflect probable correlation between alteration in trace elemental status and other pathological syndromes associated with Leishmaniasis. The possibility of considering trace elements as a diagnostic marker for a better understanding of the disease is discussed. (author)

  18. Trace elements in sera from patients with visceral leishmaniasis

    Mukhopadhyay, R.; Bhattacharya, A. [Department of Zoology, Calcutta University, Calcutta (India); Chakraborty, A.; Sudarshan, M.; Jal, P.K.; Chintalapudi, S.N. [Inter University Consortium for DAE Facilities, Calcutta Centre 3/LB-8, Bidhan Nagar, Calcutta (India); Dutta, R.K. [Schonland Research Centre for Nuclear Sciences, University of Witwatersrand, Johannesburg (South Africa)

    2000-07-01

    Trace elements are known to have pivotal role in human health and disease. Present investigation employed PIXE analysis to probe into the elemental profile of patients suffering from visceral Leishmaniasis. Remarkable alternations were observed in concentration of elements like Cl, K, Ca, Mn, Fe, Cu, Zn. The pattern of enhancement of elemental concentration corresponds to the progression of the disease. Additionally, our present data reflect probable correlation between alteration in trace elemental status and other pathological syndromes associated with Leishmaniasis. The possibility of considering trace elements as a diagnostic marker for a better understanding of the disease is discussed. (author)

  19. Leishmaniasis

    ... world’s cases of visceral leishmaniasis are in India, Bangladesh, Nepal, Sudan, and Brazil. Leishmaniasis is found in ... protecting yourself from sand fly bites. Vaccines and drugs for preventing infection are not yet available. To ...

  20. Adenosine and Immune Imbalance in Visceral Leishmaniasis: The Possible Role of Ectonucleotidases

    Rafael Paletta-Silva; José Roberto Meyer-Fernandes

    2011-01-01

    Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is responsible for most Leishmania-associated deaths. VL represents a serious public health problem that affects many countries. The immune response in leishmaniasis is very complex and is poorly understood. The Th1 versus Th2 paradigm does not appear to be so clear in visceral leishmaniasis, suggesting that other immunosuppressive or immune-evasion mechanisms contribute to the pathogenesis of VL. It has been demonstrate...

  1. Visceral leishmaniasis with endobronchial involvement in an immunocompetent adult.

    Kotsifas, Konstantinos; Metaxas, Eugenios; Koutsouvelis, Ioannis; Skoutelis, Athanassios; Kara, Panayiota; Tatsis, George

    2011-01-01

    Visceral leishmaniasis is characterized by fever, cachexia, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Cough may be a presenting symptom as well. However, pulmonary involvement is considered rare and mainly described in immunocompromised patients. We describe a case of an immunocompetent adult whose clinical presentation was dominated by cough and hemoptysis. Bronchoscopy revealed a discreet polypoid mucosal endobronchial lesion whose biopsy yielded Leishmania amastigotes within histiocytes. Transbronchial needle biopsy of a right paratracheal lymph node was also positive. Leishmania amastigotes were also found on bone marrow and liver biopsies. Treatment with IV Amphotericin B was successful. In conclusion, cough should not be overlooked as a presenting symptom of visceral leishmaniasis and may be a sign of pulmonary involvement. PMID:21577261

  2. Visceral Leishmaniasis with Endobronchial Involvement in an Immunocompetent Adult

    Konstantinos Kotsifas

    2011-01-01

    Full Text Available Visceral leishmaniasis is characterized by fever, cachexia, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Cough may be a presenting symptom as well. However, pulmonary involvement is considered rare and mainly described in immunocompromised patients. We describe a case of an immunocompetent adult whose clinical presentation was dominated by cough and hemoptysis. Bronchoscopy revealed a discreet polypoid mucosal endobronchial lesion whose biopsy yielded Leishmania amastigotes within histiocytes. Transbronchial needle biopsy of a right paratracheal lymph node was also positive. Leishmania amastigotes were also found on bone marrow and liver biopsies. Treatment with IV Amphotericin B was successful. In conclusion, cough should not be overlooked as a presenting symptom of visceral leishmaniasis and may be a sign of pulmonary involvement.

  3. Epidemiological Features of Visceral Leishmaniasis in Fars Province, Southern Iran

    MA Ghatee; G Hatam; B Sarkari

    2012-01-01

    Background: To describe the epidemiological features of pediatric visceral leishmaniasis in southern Iran.Methods: This retrospective study was carried out using local hospital records of VL patients from 2001 through 2009. Data such as age, gender, place of residence, clinical signs and symptoms, treatment, history of recurrence were recorded. The collected data were statistically analyzed using SPSS software.Results: A total of 260 cases of VL have been recorded during 2001 to 2009 in south...

  4. Recent understanding in the treatment of visceral leishmaniasis.

    Rosenthal E; Marty P.

    2003-01-01

    Visceral leishmaniasis (VL) is a severe disease associated with infection of the reticuloendothelial system by Leishmania species. The infection is acquired through sandfly bites. Recent large scale epidemics of VL in east Africa and India and the emergence of a HIV epidemic make VL a priority for the World Health Organization. Pentavalent antimonials have been cornerstone of treatment for the last six decades. The appearance of antimonial-resistance and the development of lipid formulations ...

  5. VISCERAL LEISHMANIASIS IN PETROLINA, STATE OFPERNAMBUCO, BRAZIL, 2007-2013

    Andreina de Carvalho ARAUJO; GONÇALVES, Nara Nagle Vieira Matos; Dantas-Torres, Filipe; Ferreira, Fernando; HORTA, Mauricio Claudio

    2016-01-01

    Visceral leishmaniasis is a life-threatening disease of great public health relevance in Brazil. The municipality of Petrolina is an endemic area in the State of Pernambuco, Brazil. This study was designed to assess the recent expansion of VL in the municipality of Petrolina, Pernambuco. Patients data were obtained from the Brazilian National Information System for Notifiable Diseases (SINAN). A total of 111 records from 2007 to 2013 were investigated, of which 69 were residents in Petrolina....

  6. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis.

    Cunha-Júnior, Edézio Ferreira; Martins, Thiago Martino; Canto-Cavalheiro, Marilene Marcuzzo; Marques, Paulo Roberto; Portari, Elyzabeth Avvad; Coelho, Marsen Garcia Pinto; Netto, Chaquip Daher; Costa, Paulo Roberto Ribeiro; Sabino, Katia Costa de Carvalho; Torres-Santos, Eduardo Caio

    2016-06-01

    Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. PMID:27067332

  7. Seroepidemiological and leishmanin skin test surveys of visceral leishmaniasis in south and southwest Ethiopia.

    Hailu, A; Berhe, N; Sisay, Z; Abraham, I; Medhin, G

    1996-01-01

    Sero-epidemiological and leishmanin skin test surveys of visceral leishmaniasis were carried out in eight localities of South and Southwest Ethiopia between the July 1989 and June 1992. A total number of 4870 subjects comprising semi-pastoral nomads, peasants and farm labourers were included in the study. Areas of high and low leishmanin skin test positivity were identified, with rates varying from 1.0-80.5%. An enzyme-linked immunosorbent assay was used to determine prevalence of antileishmanial antibodies. The rates varied from 1.8% to 27.8%. Age and sex related serological and leishmanin skin test profiles are described. Correlation analysis of serological and leishmanin skin test was made for data in each locality. The relationships between seroprevalence, leishmanin skin test rates and prevalence of active visceral leishmaniasis and the implications on degrees of endemicity and patterns of transmission are discussed. PMID:8674496

  8. Antissaliva Antibodies of Lutzomyia Longipalpis in area of Visceral Leishmaniasis.

    Fraga, Thiago Leite; Fernandes, Magda Freitas; Pontes, Elenir Rose Jardim Cury; Levay, Ana Paula Silva; Almeida da Cunha, Elenice Brandão; França, Adriana de Oliveira; Dorval, Maria Elizabeth Cavalheiros

    2016-07-01

    The aim of the present study was to assess the presence of antissaliva antibodies of Lutzomyia longipalpis in human hosts living in area of visceral leishmaniasis, located in the Center-West region of Brazil. The presence of antissaliva antibodies of L. longipalpis exhibited a strong correlation with the protection and development of antibodies against Leishmania sp. Of the 492 children studied, elevated antissaliva antibodies of L. longipalpis were detected in 38.4% of the participants. There was a higher percentage of positivity (64.7%) among children who exhibited anti-Leishmania sp. antibodies and among those who were positive in the delayed hypersensitivity test (34.8%). PMID:27093167

  9. Seroepidemiological Study of Visceral Leishmaniasis (Kala-azar in Ardabil Province, Iran, 1986 – 2009

    S Molaie

    2010-10-01

    Full Text Available Introduction & Objective: Visceral Leishmaniasis (kala-azar is the most important endemic disease in Northwestern Iran, particularly in Ardabil province. This study aimed to review the seroepidemiological studies which have been performed in Ardabil province during 1986-2009. Materials & Methods: In this descriptive analytical study, studies which have been carried out from 1986 through 2009 in Northwestern Iran about clinical, diagnostic and epidemiological features of Kala azar, using DAT, were reviewed. Collected data were analyzed using the SPSS software. Results: in total, 2703 of human visceral leishmaniasis were detected by direct agglutination test (DAT in Ardabil province, 1787 (66.1% of them were from Meshkin-shahr district, 837 (31% cases were from Moghan district, and 79 (2.9% cases were from Ardabil district. Ninety eight percent of the cases were under 10 years old while only 0.5% of the VL cases were ≥20 years old and 17% of them were under 1 year of age. Conclusion: Currently Kala-Azar is the most important endemic disease in Northwestern Iran, particularly in Ardabil province. Anti-Leishmania antibodies at the titers of ≥1:3200 using DAT along with clinical signs including fever, anemia and hepatosplenomegaly are considered as active visceral leishmaniasis. DAT antibody titer of 1/800 and lower and absent of clinical signs is considered as negative VL.

  10. Interstitial pulmonary alterations in visceral leishmaniasis: evaluation with high-resolution computed tomography

    Visceral leishmaniasis, also called kala-azar, is a disease caused by a protozoan, the Leishmania donovani chagasi, that comprises reticuloendothelial system with involvement of the liver, spleen and bone marrow. It is endemic in some areas of northeastern Brazil and other countries of Latin America and Africa. The pathogenesis is related to the immunologic system of patients that present with the inability to activate the phagocytosis of the macrophages. As occurs in the liver and kidneys, the lungs are also involved with interstitial abnormalities caused by Leishmania that are not dependent upon the presence of the parasite.The histopathologic changes described are the involvement of inter alveolar septal in three different phases, irregularly and diffusely throughout the whole pulmonary parenchyma. This work analyzed high-resolution computed tomography (HRCT) of the thorax in 17 patients with visceral leishmaniasis in order to detect and characterize the abnormalities described in the anatomo pathologic findings reported in the literature. The HRCT is being used to evaluate chronic interstitial lung disease in a good correlation with histologic findings. THe mos common findings detected by HRCT were the reticular opacities that include peribronchovascular interstitial thickening and interlobular septal thickening an ground-glass opacity. The HRCT suggests that similar changes to that found in alveolar structures may occur int he secondary pulmonary lobule and that the involvement in the parenchymal interstitium represents the findings reported by pathological studies in visceral leishmaniasis. (author)

  11. VISCERAL LEISHMANIASIS IN PETROLINA, STATE OFPERNAMBUCO, BRAZIL, 2007-2013

    Andreina de Carvalho ARAUJO

    2016-01-01

    Full Text Available Visceral leishmaniasis is a life-threatening disease of great public health relevance in Brazil. The municipality of Petrolina is an endemic area in the State of Pernambuco, Brazil. This study was designed to assess the recent expansion of VL in the municipality ofPetrolina, Pernambuco. Patients data were obtained from the Brazilian National Information System for Notifiable Diseases (SINAN. A total of 111 records from 2007 to 2013 were investigated, of which 69 were residents in Petrolina. The disease has predominantly affected 1-4 year old children (34.8%. Most of the patients were males (59.4%. Co-infection with human immunodeficiency virus occurred in 14.5% of the cases. The criterion most frequently used was the clinical and epidemiological confirmation (59.4%, with clinical cure in 78.3% of cases and one fatal outcome. Visceral leishmaniasis is endemic in Petrolina with transmission levels varying from moderate to high. The present study has shown the precariousness of the use of diagnostic tests in primary healthcare units, and this misuse has interfered with the diagnosis and treatment of cases.

  12. VISCERAL LEISHMANIASIS IN PETROLINA, STATE OFPERNAMBUCO, BRAZIL, 2007-2013.

    Araujo, Andreina de Carvalho; Gonçalves, Nara Nagle Vieira Matos; Dantas-Torres, Filipe; Ferreira, Fernando; Horta, Mauricio Claudio

    2016-01-01

    Visceral leishmaniasis is a life-threatening disease of great public health relevance in Brazil. The municipality of Petrolina is an endemic area in the State of Pernambuco, Brazil. This study was designed to assess the recent expansion of VL in the municipality of Petrolina, Pernambuco. Patients data were obtained from the Brazilian National Information System for Notifiable Diseases (SINAN). A total of 111 records from 2007 to 2013 were investigated, of which 69 were residents in Petrolina. The disease has predominantly affected 1-4 year old children (34.8%). Most of the patients were males (59.4%). Co-infection with human immunodeficiency virus occurred in 14.5% of the cases. The criterion most frequently used was the clinical and epidemiological confirmation (59.4%), with clinical cure in 78.3% of cases and one fatal outcome. Visceral leishmaniasis is endemic in Petrolina with transmission levels varying from moderate to high. The present study has shown the precariousness of the use of diagnostic tests in primary healthcare units, and this misuse has interfered with the diagnosis and treatment of cases. PMID:27074323

  13. Visceral leishmaniasis in the Indian subcontinent: modelling epidemiology and control.

    Anette Stauch

    2011-11-01

    Full Text Available BACKGROUND: In the Indian subcontinent, about 200 million people are at risk of developing visceral leishmaniasis (VL. In 2005, the governments of India, Nepal and Bangladesh started the first regional VL elimination program with the aim to reduce the annual incidence to less than 1 per 10,000 by 2015. A mathematical model was developed to support this elimination program with basic quantifications of transmission, disease and intervention parameters. This model was used to predict the effects of different intervention strategies. METHODS AND FINDINGS: Parameters on the natural history of Leishmania infection were estimated based on a literature review and expert opinion or drawn from a community intervention trial (the KALANET project. The transmission dynamic of Leishmania donovani is rather slow, mainly due to its long incubation period and the potentially long persistence of parasites in infected humans. Cellular immunity as measured by the Leishmanin skin test (LST lasts on average for roughly one year, and re-infection occurs in intervals of about two years, with variation not specified. The model suggests that transmission of L. donovani is predominantly maintained by asymptomatically infected hosts. Only patients with symptomatic disease were eligible for treatment; thus, in contrast to vector control, the treatment of cases had almost no effect on the overall intensity of transmission. CONCLUSIONS: Treatment of Kala-azar is necessary on the level of the individual patient but may have little effect on transmission of parasites. In contrast, vector control or exposure prophylaxis has the potential to efficiently reduce transmission of parasites. Based on these findings, control of VL should pay more attention to vector-related interventions. Cases of PKDL may appear after years and may initiate a new outbreak of disease; interventions should therefore be long enough, combined with an active case detection and include effective treatment.

  14. Mucosal relapse of visceral leishmaniasis in a child treated with anti-TNFα

    E. Jeziorski

    2015-04-01

    Full Text Available Visceral leishmaniasis is an enzootic parasitosis present across the Mediterranean Basin. Some consider it an opportunistic parasite. We report the case of a girl treated with anti-tumour necrosis factor alpha (anti-TNFα for juvenile idiopathic arthritis who had previously presented with visceral leishmaniasis. Two and a half years later, she presented a tumour-like mass in the nasal mucous membrane caused by Leishmania parasites. Leishmania infantum is classically responsible for visceral leishmaniasis, but pure mucocutaneous leishmaniasis has also been described. To our knowledge, this is the first observation of a recurrence of visceral leishmaniasis in the mucocutaneous form. The occurrence of atypical forms and presentations in those on anti-TNF therapy should be considered.

  15. Heterogeneity of environments associated with transmission of visceral leishmaniasis in South-Eastern France and implication for control strategies.

    Benoit Faucher

    Full Text Available BACKGROUND: Visceral leishmaniasis due to Leishmania infantum is currently spreading into new foci across Europe. Leishmania infantum transmission in the Old World was reported to be strongly associated with a few specific environments. Environmental changes due to global warming or human activity were therefore incriminated in the spread of the disease. However, comprehensive studies were lacking to reliably identify all the environments at risk and thereby optimize monitoring and control strategy. METHODOLOGY/FINDINGS: We exhaustively collected 328 cases of autochthonous visceral leishmaniasis from 1993 to 2009 in South-Eastern France. Leishmaniasis incidence decreased from 31 yearly cases between 1993 and 1997 to 12 yearly cases between 2005 and 2009 mostly because Leishmania/HIV coinfection were less frequent. No spread of human visceral leishmaniasis was observed in the studied region. Two major foci were identified, associated with opposite environments: whereas one involved semi-rural hillside environments partly made of mixed forests, the other involved urban and peri-urban areas in and around the region main town, Marseille. The two neighboring foci were related to differing environments despite similar vectors (P. perniciosus, canine reservoir, parasite (L. infantum zymodeme MON-1, and human host. CONCLUSIONS/SIGNIFICANCE: This unprecedented collection of cases highlighted the occurrence of protracted urban transmission of L. infantum in France, a worrisome finding as the disease is currently spreading in other areas around the Mediterranean. These results complete previous studies about more widespread canine leishmaniasis or human asymptomatic carriage. This first application of systematic geostatistical methods to European human visceral leishmaniasis demonstrated an unsuspected heterogeneity of environments associated with the transmission of the disease. These findings modify the current view of leishmaniasis epidemiology. They

  16. Patologias genitais associadas à leishmaniose visceral canina Genital pathologies associated with canine visceral leishmaniasis

    Vinícius Vasconcelos Gomes de Oliveira

    2012-09-01

    Full Text Available A leishmaniose visceral canina (LVC é uma doença parasitária crônica causada por protozoários pertencentes ao gênero Leishmania. No Brasil, a transmissão se dá, principalmente, pela ação hematófaga de insetos vetores pertencentes à subfamília Phlebotominae, particularmente, a espécie Lutzomyia longipalpis. Todavia, a trasmissão vertical e venérea da LVC está presente. Os principais sinais clínicos observados nos animais acometidos pela LVC são linfoadenomegalia, dermatopatias, hepatoesplenomegalia, onicogrifose e oftalmopatias, contudo quadros atípicos podem ser observados, inclusive com o envolvimento do sistema genital. Dessa forma, o objetivo deste artigo é realizar revisão sobre as principais patologias genitais em cães machos e fêmeas com leishmaniose visceral (LV.The canine visceral leishmaniasis (CanL is a chronic parasitic disease caused by protozoa belonging to the genus Leishmania. In Brazil, the transmission occurs mainly by the action of blood-sucking insects belonging to the subfamily Phlebotominae, particularly the Lutzomyia longipalpis species. However, the venereal and vertical transmission of the CanL is present. The main clinical signs observed in animals affected by the CanL are lymphadenopathy, skin diseases, hepatosplenomegaly, onychogryphosis and ophthalmopathy, however atypical manifestations can be observed, including the involvement of the genital system. Thus, the aim of this paper is to review on the major pathologies in genital male and female dogs with visceral leishmaniasis (VL.

  17. Epidemiology and diagnostics of visceral leishmaniasis in Serbia.

    Dakic, Z D; Pelemis, M R; Stevanovic, G D; Poluga, J L; Lavadinovic, L S; Milosevic, I S; Indjic, N K; Ofori-Belic, I V; Pavlovic, M D

    2009-12-01

    A retrospective epidemiological and diagnostic study of visceral leishmaniasis (VL) was carried out during the period 2001-2007 and included patients suspected of VL who had been diagnosed at the Parasitological Laboratory at the Institute for Infectious and Tropical Diseases, Belgrade. Diagnosis of VL was confirmed by microscopic examination of Giemsa-stained bone marrow (BM) smears. BM smears from 134 patients were examined; 22 cases of VL were diagnosed, the majority of which involved individuals who had been on holiday at the Montenegrian sea coast. The sensitivity of the initial BM smears was inadequate; this required the application of a serological test, adapted for routine use, for the diagnosis of VL. PMID:19392902

  18. Canine visceral leishmaniasis on Margarita Island (Nueva Esparta, Venezuela).

    Zerpa, O; Ulrich, M; Negrón, E; Rodríguez, N; Centeno, M; Rodríguez, V; Barrios, R M; Belizario, D; Reed, S; Convit, J

    2000-01-01

    The frequency of American visceral leishmaniasis affecting humans on Margarita Island, Venezuela, has increased in recent years, and infected dogs appear to constitute the principal source of infection. ELISA tests with Leishmania donovani promastigotes and rK39 antigen from L. chagasi in serum from 541 dogs were positive in 33.1% and 21.6% of the samples, respectively. A second blood sample taken from 50 animals after 8-10 months revealed an increase from 24% to 40% of ELISA positivity to both antigens, suggesting high susceptibility and transmission in the canine population. Among 42 serologically positive dogs, 33% of which showed clinical signs of disease, 79% were positive in polymerase chain reactions using primers specific for the L. donovani complex. Control measures including epidemiological hypersurveillance, the humane sacrifice of infected dogs, and rapid diagnosis and treatment of human cases have been initiated. PMID:11132371

  19. The unwelcome trio: HIV plus cutaneous and visceral leishmaniasis.

    Guarneri, C; Tchernev, G; Bevelacqua, V; Lotti, T; Nunnari, G

    2016-03-01

    Leishmania/Human Immunodeficiency Virus (HIV) coinfection has emerged as an extremely serious and increasingly frequent health problem in the last decades. Considering the insidious and not typical clinical picture in presence of immunosuppressive conditions, the increasing number of people travelling in endemic zones, the ability to survive, within both human and vector bodies, of the parasite, clinicians and dermatologists as the first line should be aware of these kind of "pathologic alliances," to avoid delayed diagnosis and treatment. In this setting, the occurrence of cutaneous lesions can, paradoxically, aid the physician in recognition and approaching the correct staging and management of the two (or three) diseases. Treatment of these unwelcome synergies is a challenge: apart from the recommended anti-retroviral protocols, different anti-leishmanial drugs have been widely used, according with the standard guidelines for visceral leishmaniasis (VL), with no successful treatment regimen still been established. PMID:26555699

  20. Quantification of the natural history of visceral leishmaniasis and consequences for control.

    Chapman, LA; Dyson, L.; Courtenay, O; Chowdhury, R.; Bern, C.; Medley, GF; Hollingsworth, TD

    2015-01-01

    Background Visceral leishmaniasis has been targeted for elimination as a public health problem (less than 1 case per 10,000 people per year) in the Indian sub-continent by 2017. However, there is still a high degree of uncertainty about the natural history of the disease, in particular about the duration of asymptomatic infection and the proportion of asymptomatically infected individuals that develop clinical visceral leishmaniasis. Quantifying these aspects of the disease is key for guiding...

  1. Interest in paromomycin for the treatment of visceral leishmaniasis (kala-azar)

    Wiwanitkit V

    2012-01-01

    Viroj Wiwanitkit1–31Wiwanitkit House, Bang Khae, Bangkok, Thailand; 2Hainan Medical University, Haikou, Hainan, People's Republic of China; 3Joseph Ayo Babalola University, Ikeji-Arakeji, Osun State, NigeriaAbstract: Leishmaniasis is an important vector-borne disease, and it is classified as one of the most important tropical fly-borne infections. This disease can cause two types of clinical manifestations: cutaneous forms and visceral forms. Visceral leishmaniasis, which is...

  2. Immunotherapy and immunochemotherapy in visceral leishmaniasis: promising treatments for this neglected disease

    Bruno Mendes Roatt

    2014-06-01

    Full Text Available Leishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; and visceral leishmaniasis, which is fatal if left untreated. The epidemiology and clinical features of VL vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. HIV infection, augments the severity of VL increasing the risk of developing active disease by 100 to 2320 times. An effective vaccine for humans is not yet available. Resistance to chemotherapy is a growing problem in many regions, and the costs associated with drug identification and development, make commercial production for leishmaniasis, unattractive. The toxicity of currently drugs, their long treatment course, and limited efficacy are significant concerns. For cutaneous disease, many studies have shown promising results with immunotherapy/immunochemotherapy, aimed to modulate and activate the immune response to obtain a therapeutic cure. Nowadays, the focus of many groups centers on treating canine VL by using vaccines and immunomodulators with or without chemotherapy. In human disease, the use of cytokines like Interferon-γ associated with pentavalent antimonials demonstrated promising results in patients that did not respond to conventional treatment. In mice, immunomodulation based on monoclonal antibodies to remove endogenous immunosuppressive cytokines (interleukin-10 or block their receptors, antigen-pulsed syngeneic dendritic cells, or biological products like Pam3Cys (TLR ligand has already been shown as a prospective treatment of the disease. This review addresses VL treatment, particularly immunotherapy and/or immunochemotherapy as an alternative to conventional drug treatment in experimental models, canine VL, and human disease.

  3. A canine leishmaniasis pilot survey in an emerging focus of visceral leishmaniasis: Posadas (Misiones, Argentina

    Deschutter Jorge

    2010-12-01

    Full Text Available Abstract Background An increasing number of reports are calling our attention to the worldwide spread of leishmaniasis. The urbanization of zoonotic visceral leishmaniasis (VL has been observed in different South American countries, due to changes in demographic and ecological factors. In May 2006, VL was detected for the first time in the city of Posadas (Misiones, Argentina. This event encouraged us to conduct a clinical and parasitological pilot survey on domestic dogs from Posadas to identify their potential role as reservoirs for the disease. Methods One hundred and ten dogs from the city of Posadas were included in the study. They were selected based on convenience and availability. All dogs underwent clinical examination. Symptomatology related to canine leishmaniasis was recorded, and peripheral blood and lymph node aspirates were collected. Anti-Leishmania antibodies were detected using rK39-immunocromatographic tests and IFAT. Parasite detection was based on peripheral blood and lymph node aspirate PCR targeting the SSUrRNA gene. Molecular typing was addressed by DNA sequence analysis of the PCR products obtained by SSUrRNA and ITS-1 PCR. Results According to clinical examination, 69.1% (76/110 of the dogs presented symptoms compatible with canine leishmaniasis. Serological analyses were positive for 43.6% (48/110 of the dogs and parasite DNA was detected in 47.3% (52/110. A total of 63 dogs (57.3% were positive by serology and/or PCR. Molecular typing identified Leishmania infantum (syn. Leishmania chagasi as the causative agent. Conclusions This work confirms recent findings which revealed the presence of Lutzomyia longipalpis, the vector of L. infantum in this area of South America. This new VL focus could be well established, and further work is needed to ascertain its magnitude and to prevent further human VL cases.

  4. High levels of plasma IL-10 and expression of IL-10 by keratinocytes during visceral leishmaniasis predict subsequent development of post-kala-azar dermal leishmaniasis

    Gasim, S; Elhassan, A M; Khalil, E A;

    1998-01-01

    report here that PKDL development can be predicted before treatment of visceral leishmaniasis, and that IL-10 is involved in the pathogenesis. Before treatment of visceral leishmaniasis, Leishmania parasites were present in skin which appeared normal on all patients. However, IL-10 was detected...

  5. Characteristics of bacterial sepsis among patients with visceral leishmaniasis

    Mengistu; Endris; Yegnasew; Takele; Desalegn; Woldeyohannes; Chandrashekhar; Unakal; Feleke; Moges; Moges; Tiruneh; Ermias; Diro

    2014-01-01

    Sepsis is one of the major causes and predictors of death in patients with visceral leishmaniasis(VL).Globally,incidence rate of sepsis ranged from 56-91 cases per 100000 people,with a mortality rate of 30%.Incidence of sepsis has been raised due to aging of the population and the higher incidence of immunosuppressive conditions such as HIV.VL and others.The prevalence of sepsis was reported from 4.2%to 32.3%and 14.1%in VL and VL-HIV coinfectcd patients,respectively.The mortality rate of VL patients with sepsis is greater than50%.Factors associated with sepsis in VL patients are immune suppression,pancytopenia.HIV co-infection,age 40 years old,indwelling of central venous lines and hospitalization.Although antimicrobial susceptibility patterns were not well reported,both Gram-positive and Gram-negative bacteria were isolated from patients with VL.So far.limited information is available on sepsis in VL.especially in VL-HIV coinfected patients.Therefore,further studies about sepsis prevalence,causative agents and their antibiotic patterns,and associated factors among VL and VL-HIV coinfectcd patients arc necessary.This review provides information about bacterial sepsis in patients with VL.

  6. Diagnosis of visceral leishmaniasis: developments over the last decade.

    Srividya, Gurumurthy; Kulshrestha, Arpita; Singh, Ruchi; Salotra, Poonam

    2012-03-01

    Diagnostic parameters for visceral leishmaniasis (VL), a potentially fatal parasitic disease caused by Leishmania donovani, have been redefined in the last decade with the development of serological and molecular tests, though a definitive diagnosis still banks on the century-old parasitological methods in many areas. Recombinant antigens have improved performance of serodiagnostic methods. Serology-based tests, rk39 antigen dipstick, and direct agglutination test commonly employed in the field are highly sensitive methods, however, fail to distinguish past infections. Molecular approaches have become increasingly relevant due to remarkable sensitivity, specificity, and flexibility in choice of samples. Quantitative polymerase chain reaction is a highly sensitive and specific tool used in referral labs for detection/assessment of parasite load in VL patients and subsequently in monitoring treatment response to antileishmanial agents. The method displays potential to provide threshold for distinguishing asymptomatics in endemic areas. Currently, improvement in VL diagnostics is required for successful decentralized (point-of-care) testing in field conditions and to detect VL-HIV co-infection. Techniques such as loop-mediated isothermal amplification offer a reliable molecular diagnostic method for field application. The diagnosis based on bioanalytics/biosensors promise frontiers for point-of-care VL detection after adequate standardization. This review summarizes the recent developments in VL diagnostics, drawing attention towards the need for standardization of the diagnostics across the affected regions. PMID:22065060

  7. Developments in Diagnosis of Visceral Leishmaniasis in the Elimination Era

    Singh, Om Prakash; Sundar, Shyam

    2015-01-01

    Visceral leishmaniasis (VL) is the most devastating parasitic infection worldwide causing high morbidity and mortality. Clinical presentation of VL ranges from asymptomatic or subclinical infection to severe and complicated symptomatic disease. A major challenge in the clinical management of VL is the weakness of health systems in disease endemic regions. People affected by VL mostly present to primary health care centers (PHCs), often late in their therapeutic itinerary. PHC physicians face a major challenge: they do not deal with a single disease issue but with patients presenting with complaints pointing to several diagnostic possibilities. Risk exists when some patients having less clinical manifestations are misdiagnosed. Therefore, field based accurate, sensitive, and cost effective rapid diagnostic tools that can detect disease in its mildest form are essential for effective control and reaching the goal of VL elimination. In this review, we discuss the current status and challenges of various diagnostic tools for the diagnosis of VL and assess their application in resource poor settings. PMID:26843964

  8. Visceral leishmaniasis and peritoneal tuberculosis: a case report

    Zamani A

    2009-03-01

    Full Text Available "nBackground: Leishman Denovani is an obligatory intracellular parasite that is seen such as Leishmanbody or Amustigote in intra reticolo-endothelial system. Leishmanenios is seen as sporadic-endemic or epidemic in many places in the world. In Iran in Fars state and west Azarbayjan is endemic and in other places are in sporadic form and is found in rural areas. "nCase report: A four year-old girl was admitted with visceral Leishmaniasis and Subsequently developed peritoneal tuberculosis. The patient who lived in Dashte- Moghan, complained of abdominal pain and distention and weight loss from 1.5 years ago. The titre of IFA test for leishmansis was 1/1280. Leishman body was seen in bone marrow aspiration specimen. Bone marrow culture for leishmania was negative. The specimen of acsities fluid revealed sero- fibrino- purulent exudate with lymphocyic dominancy (over 90%. No response to classic lishmanisis treatment had been started unless the patient treated with anti tuberculoid regimen.  "nConclusion: The function of the T-helper (Tht lymphocytes will decrease in Kala-azar disease. This is why there is no skin reaction to Manteaux (PPD diagnostic test the patient. The patient have been suffering from long-term malnutrition with its consequent immune defect. There was no evidences of cure in our patient during classic Kala-azar therapy. After she received anti tuberculosis therapy she revealed clinical improvement with Glucantim regimen as well.

  9. Characteristics of bacterial sepsis among patients with visceral leishmaniasis

    Mengistu Endris; Yegnasew Takele; Desalegn Woldeyohannes; Chandrashekhar Unakal; Feleke Moges; Moges Tiruneh; Ermias Diro

    2014-01-01

    Sepsis is one of the major causes and predictors of death in patients with visceral leishmaniasis (VL). Globally, incidence rate of sepsis ranged from 56-91 cases per 100000 people, with a mortality rate of 30%. Incidence of sepsis has been raised due to aging of the population and the higher incidence of immunosuppressive conditions such as HIV, VL and others. The prevalence of sepsis was reported from 4.2% to 32.3% and 14.1% in VL and VL-HIV coinfected patients, respectively. The mortality rate of VL patients with sepsis is greater than 50%. Factors associated with sepsis in VL patients are immune suppression, pancytopenia, HIV co-infection, age 40 years old, indwelling of central venous lines and hospitalization. Although antimicrobial susceptibility patterns were not well reported, both Gram-positive and Gram-negative bacteria were isolated from patients with VL. So far, limited information is available on sepsis in VL, especially in VL-HIV coinfected patients. Therefore, further studies about sepsis prevalence, causative agents and their antibiotic patterns, and associated factors among VL and VL-HIV coinfected patients are necessary. This review provides information about bacterial sepsis in patients with VL.

  10. Canine Visceral Leishmaniasis in Boyer Ahmad District, Kohgiluyeh & Boyer Ahmad Province, Southwest of Iran

    V Barati

    2012-12-01

    Full Text Available Background: Mediterranean type of visceral leishmaniasis (VL is present in different parts of Iran. Several studies have identified dogs as the main reservoirs of the VL caused by Leishmania infantum in Iran and other Mediterranean regions. This study aimed to determine the seroprevalence of canine visceral leishmaniasis as animal reservoir host for human visceral leishmaniasis in Boyer Ahmad dis­trict in southwest of Iran.Methods: A seroepidemiological study was carried out to determine the seroprevalence of canine visceral leishmaniasis (CVL among ownership dogs by using direct agglutination test (DAT in 23 of 182 villages of Boyer Ahmad district, during August 2009 to August 2010. One hundred and seventy serum samples from ownership dogs were selected by multi-stage cluster sampling in villages of Boyer Ahmad district. All samples were tested by DAT and anti-Leishmania antibodies titers at ≥ 1:320 was considered as positive.Results: Of the 170 serum samples, 10% were positive by DAT at titers of 1:320 and higher. No statistical significant difference was found between male (10.7% and female (8.3% seroprevalence. The highest seroprevalence rate (15.1% was observed among the ownership dogs of four to seven years age. Altogether, seventeen (25.4% of the seropositive dogs had clinical signs and symptoms.Conclusion: It seems that Boyer Ahmad district is an endemic area for canine visceral leishmaniasis in Iran.

  11. Interstitial pulmonary alterations in visceral leishmaniasis: evaluation with high-resolution computed tomography; Alteracoes pulmonares intersticiais na leishmaniose visceral: avaliacao pela tomografia computadorizada de alta resolucao

    Costa, Norma Selma Santos; Cerri, Giovanni Guido [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Dept. de Radiologia

    1999-08-01

    Visceral leishmaniasis, also called kala-azar, is a disease caused by a protozoan, the Leishmania donovani chagasi, that comprises reticuloendothelial system with involvement of the liver, spleen and bone marrow. It is endemic in some areas of northeastern Brazil and other countries of Latin America and Africa. The pathogenesis is related to the immunologic system of patients that present with the inability to activate the phagocytosis of the macrophages. As occurs in the liver and kidneys, the lungs are also involved with interstitial abnormalities caused by Leishmania that are not dependent upon the presence of the parasite. The histopathologic changes described are the involvement of inter alveolar septal in three different phases, irregularly and diffusely throughout the whole pulmonary parenchyma. This work analyzed high-resolution computed tomography (HRCT) of the thorax in 17 patients with visceral leishmaniasis in order to detect and characterize the abnormalities described in the anatomo pathologic findings reported in the literature. The HRCT is being used to evaluate chronic interstitial lung disease in a good correlation with histologic findings. The most common findings detected by HRCT were the reticular opacities that include peribronchovascular interstitial thickening and interlobular septal thickening an ground-glass opacity. The HRCT suggests that similar changes to that found in alveolar structures may occur in the secondary pulmonary lobule and that the involvement in the parenchymal interstitium represents the findings reported by pathological studies in visceral leishmaniasis. (author)

  12. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis

    Bunn, Patrick T.; Singh, Neetu; Chauhan, Shashi Bhushan; Sheel, Meru; Amante, Fiona H.; Montes de Oca, Marcela; Edwards, Chelsea L.; Ng, Susanna S.; Best, Shannon E.; Haque, Ashraful; Beattie, Lynette; Hafner, Louise M.; Sacks, David; Nylen, Susanne; Sundar, Shyam; Engwerda, Christian R.

    2016-01-01

    Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR) on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL) patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of combining different

  13. Cost of Pediatric Visceral Leishmaniasis Care in Morocco

    Alonso, Sergi; Sicuri, Elisa; Laamrani El Idrissi, Abderahmane; Nejjari, Chakib; Picado, Albert

    2016-01-01

    Background Visceral leishmaniasis (VL) is a neglected parasitic disease that is fatal if left untreated. VL is endemic in Morocco and other countries in North Africa were it mainly affects children from rural areas. In Morocco, the direct observation of Leishmania parasites in bone marrow aspirates and serological tests are used to diagnose VL. Glucantime is the first line of treatment. The objective of this study was to report the costs associated to standard clinical management of pediatric VL from the provider perspective in Morocco. As a secondary objective we described the current clinical practices and the epidemiological characteristics of pediatric VL patients. Methods From March to June 2014 we conducted a survey in eight hospitals treating pediatric VL patients in Morocco. A pro-forma was used to collect demographic, clinical and management data from medical records. We specifically collected data on VL diagnosis and treatment. We also estimated the days of hospitalization and the time to start VL treatment. Costs were estimated by multiplying the use of resources in terms of number of days in hospital, tests performed and drugs provided by the official prices. For patients receiving part of their treatment at Primary Health Centers (PHC) we estimated the cost of administering the Glucantime as outpatient. We calculated the median cost per VL patient. We also estimated the cost of managing a VL case when different treatment strategies were applied: inpatient and outpatient. Results We obtained data from 127 VL patients. The median total cost per pediatric VL case in Morocco is 520 US$. The cost in hospitals applying an outpatient strategy is significantly lower (307 US$) than hospitals keeping the patients for the whole treatment (636 US$). However the outpatient strategy is not yet recommended as VL treatment for children in the Moroccan guidelines. VL diagnosis and treatment regimens should be standardized following the current guidelines in Morocco

  14. [Visceral leishmaniasis as a threat for non-endemic countries].

    Górski, Stanisław; Wiercińska-Drapało, Alicja

    2009-01-01

    Global warming, globalisation, and constantly increasing number of people involved in long-distance tourism and travel to exotic destinations are likely to increase the number of cases of exotic diseases "imported" to nonendemic countries. One of the often forgotten and neglected diseases has been visceral leishmaniasis (VL or kala-azar). The disease is endemic to 62 countries, with India and Sudan accounting for the majority of the cases. It is typically fatal if left untreated. Each year about 500 000 new cases are reported worldwide, and 50 000 die as a result of the disease. Kala-azar is present in the Mediterranean Europe and 70% of cases are imported to non-endemic countries of European Union from that area. Immunocompromised status of patients, like HIV carriers are the principal prospective target for kala-azar. HIV/VL-coinfected patients have significantly higher relapse rates and decreased life expectancy. There is no formal system of reporting imported cases in Europe, except from Germany. In non-endemic countries, including Poland, there is usually the substantial delay between the onset of symptoms and the final diagnosis, with an average exceeding 3 months. This fact suggests that physicians are not familiar with leishmania infections. Despite progress in vaccine development, the only way to prevent the infection is avoiding sandfly bites. Mosquito nets, wearing appropriate clothes and repellents containing DEET (diethyl toluamide) can reduce number of bites and protect also from the other vector-borne diseases like malaria or dengue. Education concerning kala-azar risk and ways of the disease prevention is a needed for tourists and the other travelers. PMID:19856834

  15. Brote urbano de leishmaniasis visceral en Neiva, Colombia

    Pilar Zambrano-Hernandez

    2015-07-01

    Full Text Available Objetivo Estudiar clínica y epidemiológicamente focos de leishmaniasis visceral (LV urbana en Neiva (Colombia. Materiales y Métodos Seis niños consultaron por hepato-esplenomegalia. Presentaban anemia y leucopenia. Se realizó biopsia por aspiración de medula ósea (5 pacientes y de bazo (1 paciente. Se hizo búsqueda activa de casos en la comunidad y de anticuerpos anti-Leishmania infantum por inmunofluorescencia indirecta (IFI en los sintomáticos y en reservorios caninos (IFI, rK39. Se hicieron visitas domiciliarias para educación comunitaria y búsqueda de vectores. Los pacientes recibieron Miltefosina, Anfotericina B o Glucantime®. Resultados Se confirmó LV en siete niños. En seis, el aspirado de medula ósea o bazo demostró amastigotes. La IFI fue positiva en 4 pacientes y negativa en 3. Un niño se detectó por búsqueda activa comunitaria, con clínica de LV, confirmada por IFI (1:32. La miltefosina no fue útil en 6 de los 7 casos. La Anfotericina B liposomal o deoxicolato, curó 6 pacientes y el Glucantime® uno. La seroprevalencia en 1182 caninos (IFI y rK39 fue de 6.1 %; los animales positivos fueron sacrificados. Se demostró Lu. longipalpis, vector de LV, en el peridomicilio. Conclusiones Demostramos LV urbana en dos comunas de Neiva. La confirmación diagnóstica incluyó aspiración de medula ósea e IFI. La Miltefosina no fue útil. La Anfotericina B liposomal fue la terapia ideal. Para controlar la LV es necesario hacer BAC, educación comunitaria, control de vectores y reservorios.

  16. Cost of Pediatric Visceral Leishmaniasis Care in Morocco.

    Nabil Tachfouti

    Full Text Available Visceral leishmaniasis (VL is a neglected parasitic disease that is fatal if left untreated. VL is endemic in Morocco and other countries in North Africa were it mainly affects children from rural areas. In Morocco, the direct observation of Leishmania parasites in bone marrow aspirates and serological tests are used to diagnose VL. Glucantime is the first line of treatment. The objective of this study was to report the costs associated to standard clinical management of pediatric VL from the provider perspective in Morocco. As a secondary objective we described the current clinical practices and the epidemiological characteristics of pediatric VL patients.From March to June 2014 we conducted a survey in eight hospitals treating pediatric VL patients in Morocco. A pro-forma was used to collect demographic, clinical and management data from medical records. We specifically collected data on VL diagnosis and treatment. We also estimated the days of hospitalization and the time to start VL treatment. Costs were estimated by multiplying the use of resources in terms of number of days in hospital, tests performed and drugs provided by the official prices. For patients receiving part of their treatment at Primary Health Centers (PHC we estimated the cost of administering the Glucantime as outpatient. We calculated the median cost per VL patient. We also estimated the cost of managing a VL case when different treatment strategies were applied: inpatient and outpatient.We obtained data from 127 VL patients. The median total cost per pediatric VL case in Morocco is 520 US$. The cost in hospitals applying an outpatient strategy is significantly lower (307 US$ than hospitals keeping the patients for the whole treatment (636 US$. However the outpatient strategy is not yet recommended as VL treatment for children in the Moroccan guidelines. VL diagnosis and treatment regimens should be standardized following the current guidelines in Morocco.

  17. Suppression of host PTEN gene expression for Leishmania donovani survival in Indian visceral leishmaniasis.

    Sudarshan, Medhavi; Singh, Toolika; Singh, Bhawana; Chakravarty, Jaya; Sundar, Shyam

    2016-05-01

    Lipid phosphatase, PTEN is amongst the host gene actively involved in determining disease susceptibility. Expression of pten and other genes in vicinity egr1 &4e-bp1 were evaluated in splenic tissue before and after treatment in visceral leishmaniasis patients. Lower expression of egr1 in correlation with pten suppressed 4e-bp1 gene in active cases. The higher levels of pten mRNA expression post treatment confirmed its role in effective clearance of Leishmania. Therefore, it is hypothesized that lower mRNA expression of pten is due to suppression of egr1 activates PI3K signaling bestowing host the ability to cope up infection and continue its normal metabolic machinery. PMID:26774334

  18. Distinct antigen recognition pattern during zoonotic visceral leishmaniasis in humans and dogs

    Goto, Yasuyuki; Howard, Randall F.; Bhatia, Ajay; Trigo, Joelma; Nakatani, Maria; Eduardo M. Netto; Reed, Steven G.

    2008-01-01

    Leishmania infantum is a causative agent of endemic zoonotic visceral leishmaniasis (VL) in regions of South America and the Mediterranean. Dogs are the major reservoirs for Leishmania infantum in these regions, and control of disease in dogs could have a significant impact on human disease. Although dogs share many symptoms of VL with humans as a result of L. infantum infection, they also show some unique clinical manifestations, which are often a combination of visceral and cutaneous leishm...

  19. Efficacies of KY62 against Leishmania amazonensis and Leishmania donovani in Experimental Murine Cutaneous Leishmaniasis and Visceral Leishmaniasis

    Al-Abdely, Hail M.; Graybill, John R.; Bocanegra, Rosie; Najvar, Laura; Montalbo, Eleanor; Regen, Steven L.; Melby, Peter C.

    1998-01-01

    Current therapy for leishmaniasis is unsatisfactory because parenteral antimonial salts and pentamidine are associated with significant toxicity and failure rates. We examined the efficacy of KY62, a new, water-soluble, polyene antifungal, against cutaneous infection with Leishmania amazonensis and against visceral infection with Leishmania donovani in susceptible BALB/c mice. Mice were infected with L. amazonensis promastigotes in the ear pinna and in the tail and were treated with KY62 or a...

  20. Culling Dogs in Scenarios of Imperfect Control: Realistic Impact on the Prevalence of Canine Visceral Leishmaniasis

    Costa, Danielle N. C. C.; Codeço, Cláudia T.; Silva, Moacyr A.; Werneck, Guilherme L.

    2013-01-01

    Background Visceral leishmaniasis belongs to the list of neglected tropical diseases and is considered a public health problem worldwide. Spatial correlation between the occurrence of the disease in humans and high rates of canine infection suggests that in the presence of the vector, canine visceral leishmaniasis is the key factor for triggering transmission to humans. Despite the control strategies implemented, such as the sacrifice of infected dogs being put down, the incidence of American visceral leishmaniasis remains high in many Latin American countries. Methodology/Principal Findings Mathematical models were developed to describe the transmission dynamics of canine leishmaniasis and its control by culling. Using these models, imperfect control scenarios were implemented to verify the possible factors which alter the effectiveness of controlling this disease in practice. Conclusions/Significance A long-term continuous program targeting both asymptomatic and symptomatic dogs should be effective in controlling canine leishmaniasis in areas of low to moderate transmission (R0 up to 1.4). However, the indiscriminate sacrifice of asymptomatic dogs with positive diagnosis may jeopardize the effectiveness of the control program, if tests with low specificity are used, increasing the chance of generating outrage in the population, and leading to lower adherence to the program. Therefore, culling must be planned accurately and implemented responsibly and never as a mechanical measure in large scale. In areas with higher transmission, culling alone is not an effective control strategy. PMID:23951375

  1. Field evaluation of latex agglutination test for detecting urinary antigens in visceral leishmaniasis in Sudan.

    El-Safi, S H; Abdel-Haleem, A; Hammad, A; El-Basha, I; Omer, A; Kareem, H G; Boelaert, M; Chance, M; Hommel, M

    2003-07-01

    A latex agglutination test to detect urinary antigens for visceral leishmaniasis (VL) was studied. In 204 patients with suspected VL, KAtex had a sensitivity of 95.2% with good agreement with microscopy smears but poor agreement with 4 different serology tests. It was also positive in 2 confirmed VL cases co-infected with HIV. In all K4tex-positive confirmed cases actively followed up after treatment, the test became negative 1 month after completion of treatment. While IC4tex had a specificity of 100% in healthy endemic and non-endemic controls, the direct agglutination test (DAT) was positive in 14% of the KAtex-negative healthy endemic controls. KAtex is a simple addition to the diagnostics of VL particularly at field level and as a complementary test for the diagnosis of VL in smear-negative cases with positive DAT results. PMID:15748081

  2. Epidemiologic aspects of American visceral leishmaniasis in an endemic focus in Eastern Venezuela.

    Zulueta, A M; Villarroel, E; Rodriguez, N; Feliciangeli, M D; Mazzarri, M; Reyes, O; Rodriguez, V; Centeno, M; Barrios, R M; Ulrich, M

    1999-12-01

    An endemic focus of American visceral leishmaniasis (AVL) in eastern Venezuela has been evaluated in terms of patients (n = 48), immunologic reactivity to Leishmania in household contacts (n = 187) and neighborhood controls (n = 170), detection of Leishmania (L. donovani complex) in dogs and wild animals by the polymerase chain reaction (PCR) and characteristics of the sandfly population. The male:female ratio of patients was 1.18:1; 89.6% were Didelphis marsupialis), and a black rat (Rattus rattus). Lutzomyia longipalpis and Lu. evansi, both implicated in the transmission of AVL, were identified among the 386 sand flies examined. These observations provide the bases for an active control program as well as further studies of reservoirs and vector-host relationships in this area. PMID:10674675

  3. Visceral leishmaniasis hos to børn efter ferie i Sydeuropa

    Castberg, Filip Christian; Poulsen, Anja; Petersen, Bodil Laub;

    2013-01-01

    Pancytopenia, fever and splenomegaly are frequent causes for referrals to paediatric haematology departments, on the suspicion of acute leukaemia. We report two cases of Danish children with the tropical disease visceral leishmaniasis (VL) contracted on short vacations in Southern Europe. One of ...

  4. Survey of feline visceral leishmaniasis in Azarshahr area, north west of Iran, 2013.

    Fatollahzadeh, Mohammad; Khanmohammadi, Majid; Bazmani, Ahad; Mirsamadi, Nasrin; Jafari, Rasool; Mohebali, Mehdi; Nemati, Taher; Fallah, Esmail

    2016-09-01

    Leishmania infantum is a causative agent of visceral leishmaniasis or kala-azar, which is endemic in some part of Iran. Azarshahr city located in East Azerbaijan province, North West of Iran, which is endemic for visceral leishmaniasis. This study aimed to investigate the possible reservoir role of cats for visceral leishmaniasis in the Azarshahr area. Totally 65 cats have been trapped alive from villages of Azarshahr county and their serum samples subjected to direct agglutination test (DAT) for L. infantum antibodies. Giemsa stained impression smears have been prepared for parasitological examination of spleen and liver tissue. Also liver and spleen samples of the cats have been cultured in Novy-MacNeal-Nicolle (NNN) medium and also used for PCR. None from 65 samples was positive in NNN culture, PCR and microscopic examination. Fifteen (23.07 %) out of 65 serum samples showed Leishmania specific antibody agglutination at 1:320 dilution or above, but all considered as negative because none of them confirmed by Giemsa stained smears, PCR and NNN culture. According to the findings of the present study, cats are not a reservoir for visceral leishmaniasis in the Azarshahr area. PMID:27605767

  5. Genome-wide scan for visceral leishmaniasis susceptibility genes in Brazil

    Jamieson, SE; Miller, EN; Peacock, CS; Fakiola, M; Wilson, ME; Bales-Holst, A; Shaw, M-A; Silveira, F.; Shaw, JJ; Jeronimo, SM; Blackwell, JM

    2006-01-01

    A genome-wide scan was conducted for visceral leishmaniasis in Brazil. Initially, 405 markers were typed in 22 multicase pedigrees (28 nuclear families; 174 individuals; 66 affected. Nonparametric multipoint analysis detected 9 chromosomal regions with provisional evidence (LOD scores 0.95 to 1.66; 0.003​

  6. Cutaneous and post kala-azar dermal leishmaniasis caused by Leishmania infantum in endemic areas of visceral leishmaniasis, northwestern Iran 2002–2011: a case series

    Badirzadeh, Alireza; Mehdi MOHEBALI; Ghasemian, Mehrdad; Amini, Hassan; Zarei, Zabiholah; AKHOUNDI, Behnaz; HAJJARAN, Homa; Emdadi, Dariush; Molaei, Soheila; Kusha, Ahmad; ALIZADEH, Saber

    2013-01-01

    Visceral leishmaniasis (VL) is endemic in Northwest and southern Iran. Reports of cutaneous leishmaniasis (CL) in Northwest areas are rare, and its etiological agents are unknown. In the current study, we report six CL and two post kala-azar dermal leishmaniasis (PKDL) cases caused by Leishmania infantum from endemic areas of VL in the Northwest. Smears were made from skin lesions of 30 suspected patients in 2002–2011, and CL was determined by microscopy or culture. Leishmania spp. were ident...

  7. Leishmaniasis

    Kemp, M; Theander, T G

    2000-01-01

    Leishmania parasites are obligate intracellular protozoa, that produce clinical pictures, ranging from localised, self-healing ulcers to systemic, lethal diseases. The diseases caused by the parasites can be divided into cutaneous, mucocutaneous, and visceral leishmaniasis. Recovery from the infe......Leishmania parasites are obligate intracellular protozoa, that produce clinical pictures, ranging from localised, self-healing ulcers to systemic, lethal diseases. The diseases caused by the parasites can be divided into cutaneous, mucocutaneous, and visceral leishmaniasis. Recovery from...... the infection often leaves lifelong immunity. Leishmaniasis may occur in individuals who have been to the Mediterranean countries, the countries on the Horn of Africa, the Arabian Peninsula, parts of Asia, and South and Central America. Co-infection of Leishmania parasites and HIV is a special problem...

  8. High levels of C-reactive protein in the peripheral blood during visceral leishmaniasis predict subsequent development of post kala-azar dermal leishmaniasis

    Gasim, S; Theander, T G; ElHassan, A M

    2000-01-01

    Post kala-azar dermal leishmaniasis (PKDL) is a known sequel to visceral leishmaniasis in India and East Africa, and in Sudan about 50% of the kala-azar patients develop PKDL. In this study we followed kala-azar patients from diagnosis and up to 2 years after initiation of treatment. During the...... keratinocytes during visceral leishmaniasis predict subsequent development of PKDL. The method however requires expensive equipment and reagents. The results of the present study indicate that kala-azar patients, who have a high risk of developing PKDL after treatment can be identified by measuring plasma CRP....

  9. Comparative Study of rK39 Leishmania Antigen for Serodiagnosis of Visceral Leishmaniasis: Systematic Review with Meta-Analysis

    Maia, Zuinara; Lírio, Monique; Mistro, Sóstenes; Mendes, Carlos Maurício Cardeal; Mehta, Sanjay R; Badaro, Roberto

    2012-01-01

    Background The rK39 recombinant protein is derived from a specific antigen produced by the Leishmania donovani complex, and has been used in the last two decades for the serodiagnosis of visceral leishmaniasis. We present here a systematic review and meta-analysis of studies evaluating serologic assays to diagnose visceral leishmaniasis to determine the accuracy of rK39 antigen in comparison to the use of other antigen preparations. Methodology/Principal Findings A systematic review with meta...

  10. A comparison of four DNA extraction protocols for the analysis of urine from patients with visceral leishmaniasis

    Maria Almerice Lopes da Silva; Zulma Medeiros; Cynthia Regina Pedrosa Soares; Elis Dionísio da Silva; Demócrito de Barros Miranda-Filho; Fábio Lopes de Melo

    2014-01-01

    Introduction Polymerase chain reaction (PCR) may offer an alternative diagnostic option when clinical signs and symptoms suggest visceral leishmaniasis (VL) but microscopic scanning and serological tests provide negative results. PCR using urine is sensitive enough to diagnose human visceral leishmaniasis (VL). However, DNA quality is a crucial factor for successful amplification. Methods A comparative performance evaluation of DNA extraction methods from the urine of patients with VL using...

  11. A case of conventional treatment failure in visceral leishmaniasis: leukocyte distribution and cytokine expression in splenic compartments

    dos-Santos, Washington LC; Carla PAGLIARI; Santos, Lina G; Almeida, Valter A; e Silva, Thiago LV; Coutinho Jr, João de J; Souza, Tulio; Duarte, Maria IS; de Freitas, Luiz AR; Costa, Carlos HN

    2014-01-01

    Background In this paper we study the distribution of leukocyte populations and of cytokine-producing cells in the spleen of a patient with visceral leishmaniasis resistant to clinical treatment. It is the first attempt to compare the distribution of leukocyte populations and cytokine-producing cells in the splenic compartments of a patient with visceral leishmaniasis with those observed in patients without the disease. Case presentation A 25-year-old male, farmer, was hospitalized on several...

  12. The Contribution of Immune Evasive Mechanisms to Parasite Persistence in Visceral Leishmaniasis

    de Freitas, Elisangela Oliveira; Leoratti, Fabiana Maria de Souza; Freire-de-Lima, Célio Geraldo; Morrot, Alexandre; Feijó, Daniel Ferreira

    2016-01-01

    Leishmania is a genus of protozoan parasites that give rise to a range of diseases called Leishmaniasis that affects annually an estimated 1.3 million people from 88 countries. Leishmania donovani and Leishmania (L.) infantum chagasi are responsible to cause the visceral leishmaniasis. The parasite can use assorted strategies to interfere with the host homeostasis to establish persistent infections that without treatment can be lethal. In this review, we highlight the mechanisms involved in the parasite subversion of the host protective immune response and how alterations of host tissue physiology and vascular remodeling during VL could affect the organ-specific immunity against Leishmania parasites. PMID:27148272

  13. Infecções experimentaes na Leishmaniose visceral americana Experimental infections in american visceral leishmaniasis

    Aristides Marques da Cunha

    1938-01-01

    sôro-agglutinação, conforme mostramos em trabalho anterior, não permite a separação das especies do genero Leishmania, pois todas ellas, quando recentemente isoladas, possuem identica constituição antigenica, que se modifica depois, pela conservação longo tempo em cultura. É esse facto, que deu logar ás conclusões contradictorias a que chegaram os autores que se ocuparam do assumpto bem como os primeiros resultados que obtivemos. Deante de todos esses factos, nos julgamos autorizados a concluir como já fizemos anteriormente, que o agente da Leishmaniose visceral americana é identico á Leishmania infantum. Ao terminar, queremos deixar consignados nossos agradecimentos ao Dr. E. chagas, por ter posto a nossa disposição as culturas de Leishmania por elle isoladas, tornando possivel deste modo, a execução do presente trabalho.With cultures isolated from cases of american visceral leishmaniasis we succeeded in obtaining experimental infections in hamsters (Cricetus cricetus, rhesus monkeys (Macaca mullata and dogs. Hamsters were infected with strains obtained from man and dogs, the intraperitoneal way having been always employed. When cultures recently isolated are used, infection is obtained practically in 100% of the animals inoculated. The first negative results obtained by us may be explained by the use of cultures isolated some time before (about 7 months 0 and which had lost already their virulence. In some cases external lesions are observed represented by alterations of the skin and swelling of the paws. The skin lesions are observed on the ventral surface and consist in depilation, erythema and exudation. The skin thus affected shows to be extremely friable, rupturing at the movements of the animal when hold. On post-mortem examination, besides the lesions pointed out, the animals present enlargement of the spleen. The parasites are very numerous in the spleen, liver, bone marrow, etc. The changed skin shows considerable hypertrophy of the

  14. Paediatric visceral leishmaniasis: experience of a paediatric referral center 1990-2009

    Dionísio, MT; Dias, A; Rodrigues, F.; Félix, M.; Estevão, MH

    2011-01-01

    INTRODUCTION: Visceral Leishmaniasis (VL) is a systemic infection, endemic in many parts of the world, including Portugal. The aim is to review all cases of VL admitted to our hospital. PATIENTS AND METHODS: Retrospective analysis of all cases of VL admitted to a Level III Paediatric Hospital, between January 1990 and December 2009 (20 years). Demographic, epidemiological, clinical, laboratorial, therapeutic and follow-up data were analysed. RESULTS: During the study period, 54 childr...

  15. Imported Visceral Leishmaniasis: Diagnostic Dilemmas and Comparative Analysis of Three Assays

    Iqbal, Jamshaid; Hira, Parsotam R.; Saroj, Grover; Philip, Reeni; Ali, Faiza Al-; J. Madda, Patrick; Sher, Ali

    2002-01-01

    The present study evaluates the performances of three noninvasive serological assays for the detection of immunoglobulin G antibodies to leishmania antigen for the diagnosis of imported cases of kala azar (visceral leishmaniasis [VL]) in a country, Kuwait, where the disease is not endemic. A total of 323 individuals including 21 patients with documented cases of VL, 72 individuals with suspected cases of VL, 155 patients with other parasitic infections, and 75 healthy control individuals were...

  16. Household-cost-of-illness of visceral leishmaniasis in Bihar, India

    Sundar, S.; Arora, R.; Singh, S.P.; Boelaert, M; Varghese, B.

    2010-01-01

    Summary Objective To determine the cost of kala-azar (KA) to patients in Bihar, India. Method A semi-structured questionnaire was used to collect costs of illness - direct (medical; non-medical) and indirect costs (work days lost). After screening the community known to be endemic for visceral leishmaniasis (VL), households (HHs) with VL were recruited which reported a case of KA who received treatment between September 2005 and September 2006. The total costs were calculated as a summation o...

  17. Peripheral Blood Buffy Coat Smear: a Promising Tool for Diagnosis of Visceral Leishmaniasis

    Salam, M. Abdus; Khan, M. Gulam Musawwir; Bhaskar, Khondaker Rifat Hasan; Afrad, Mokibul Hassan; Huda, M Mamun; Mondal, Dinesh

    2012-01-01

    Confirmative diagnosis of visceral leishmaniasis (VL) is still a challenge at the primary health care facilities in most of the rural areas of endemicity in the Indian subcontinent. Conventional methods for parasitological confirmation are risky and require skilled personnel, and hence they are unavailable to the poor people in the regions of endemicity. Buffy coat smear microscopy, as a minimally invasive, simple alternative for the parasitological diagnosis of VL, was evaluated in this pros...

  18. Comparison between Conventional and Real-Time PCR Assays for Diagnosis of Visceral Leishmaniasis

    Mariana R. Pereira

    2014-01-01

    Full Text Available The diagnosis of visceral leishmaniasis (VL is a challenging issue and several studies worldwide have evaluated the different tools to reach a diagnostic solution. The polymerase chain reaction (PCR has proven to be effective in detecting the genome of Leishmania species in different biological samples. In this study, we compared the conventional PCR and real-time PCR using the Sybr Green system and their application in molecular diagnosis of visceral leishmaniasis in peripheral blood as a biological sample. The genus-specific conserved region of kinetoplast DNA (kDNA was the target of amplification. We studied 30 samples from patients with suspect of visceral leishmaniasis who were treated by the Medical Clinic of Santa Casa de Belo Horizonte Hospital, Brazil. Among the samples studied, 19 had a confirmed diagnosis for VL by serology and/or by clinical findings. Among these 19 samples, 63% (n=12 presented positive results for serology and 79% (n=15 positive results in both PCR methodologies. This fact suggests that the PCR technique can assist in the diagnosis of visceral leishmaniasis in patients who do not have detectable antibodies by serology but can present the genome of the parasite circulating in whole blood. Also, it was possible to observe that there was conformity between the results of the techniques of cPCR and qPCR using the Sybr Green system in 100% of samples analyzed. These data suggest that both PCR techniques were equally effective for detection of the genome of the parasite in the patient’s blood.

  19. Visceral Leishmaniasis: A Differential Diagnosis to Remember after Bone Marrow Transplantation

    2014-01-01

    Leishmania infection in immunocompromised hosts is reported in the literature, mostly concerning human immunodeficiency virus infected patients. It is not well characterized in the context of stem cell transplantation. We report a rare case clinical case of visceral leishmaniasis after allogeneic bone marrow transplantation. A 50-year-old Caucasian male was referred to allogeneic bone marrow transplantation with a high-risk acute lymphoblastic B leukemia in first complete remission. Allogenei...

  20. Safety and Effectiveness of Amphotericin B Deoxycholate for the Treatment of Visceral Leishmaniasis in Uganda.

    Mueller, Y; Nguimfack, A; Cavailler, Philippe; Couffignal, Sophie; Rwakimari, J B; Loutan, Louis; Chappuis, Francois

    2008-01-01

    Between September 2003 and April 2004, the supply of antimonial drugs to Amudat Hospital, in north-eastern Uganda, was interrupted and all cases of visceral leishmaniasis presenting at the hospital could only be treated with amphotericin B deoxycholate (AmB). This allowed the safety and effectiveness of the AmB to be evaluated, in comparison with an historical cohort of patients treated, at the same hospital, with meglumine antimoniate (Sb(V)). Demographic and clinical data were collected bef...

  1. Canine antibody response to Lutzomyia longipalpis saliva in endemic area of visceral leishmaniasis.

    Luís Fábio da Silva Batista; Vânia Lúcia Ribeiro da Matta; Thaise Yumie Tomokane; Acácio Duarte Pacheco; Fernando Tobias Silveira; Claudio Nazaretian Rossi; Mary Marcondes; Márcia Dalastra Laurenti

    2016-01-01

    Abstract: INTRODUCTION: Canine exposure to Lutzomyia longipalpis bites and the potential of Leishmania infantum transmissibility for the vector were evaluated. METHODS Immunoglobulin G (IgG) anti-Lu longipalpis saliva and -L. infantum, and blood parasite load were determined in dogs from endemic areas of visceral leishmaniasis. RESULTS Blood parasitism was similar between symptomatic and asymptomatic dogs. IgG anti-L. infantum was higher in symptomatic dogs, but IgG anti-Lu. longipalpis ...

  2. The Economic Value of a Visceral Leishmaniasis Vaccine in Bihar State, India

    Lee, Bruce Y.; Bacon, Kristina M.; Shah, Mirat; Kitchen, Sara Beth; Connor, Diana L.; Slayton, Rachel B.

    2012-01-01

    Visceral leishmaniasis (VL) is responsible for substantial morbidity and mortality and current available treatments have many limitations. The ability of VL infection to generate life-long immunity offers promise for the development of a VL vaccine. A VL vaccine candidate has recently completed phase I clinical trials. We constructed a computer simulation model to determine the potential economic value of a VL vaccine in the endemic region of Bihar state, India. Results found a potential vacc...

  3. Persistence of Leishmania donovani Antibodies in Past Visceral Leishmaniasis Cases in India ▿

    Gidwani, Kamlesh; Picado, Albert; Ostyn, Bart; Singh, Shri Prakash; Kumar, Rajiv; Khanal, Basudha; Lejon, Veerle; Chappuis, François; Boelaert, Marleen; Sundar, Shyam

    2010-01-01

    The persistence of anti-Leishmania donovani antibodies in past visceral leishmaniasis (VL) cases was retrospectively assessed by means of the direct agglutination test (DAT) and the rK39 enzyme-linked immunosorbent assay (ELISA). Antibody titers remained high for an extended period of time in past cases of VL. These results highlight the need to carefully elicit the history of patients with VL symptoms.

  4. The subclinical form of experimental visceral leishmaniasis in dogs

    G. G. S. Oliveira; F. Santoro; M. Sadigursky

    1993-01-01

    Pathological aspects of a subclinical form of experimental canine leishmaniasis is reported here for the first time. Fifteen mongrel dogs were used in the present study. Eight dogs were infected and seven were used as control. Four of the control dogs were inoculated with spleen cells from non-infected hamsters. The eight mongrel dogs inoculated intravenously with amastigotes forms of Leishmania chagasi envolved for periods as long as 25 months without any clinical characteristic sign of clas...

  5. Effective immunotherapy against canine visceral leishmaniasis with the FML-vaccine.

    Borja-Cabrera, Gulnara Patricia; Cruz Mendes, Amanda; Paraguai de Souza, Edilma; Hashimoto Okada, Lilian Y; de A Trivellato, Fernando Antonio; Kawasaki, Jarbas Kiyoshi A; Costa, Andreia Cerqueira; Reis, Alexandre Barbosa; Genaro, Odair; Batista, Leopoldina Maria Melo; Palatnik, Marcos; Palatnik-de-Sousa, Clarisa Beatriz

    2004-06-01

    The potential effect of the fucose mannose ligand (FML)-vaccine on immunotherapy of canine visceral leishmaniasis was assayed on five mongrel dogs experimentally infected with Leishmania donovani and on 21 Leishmania chagasi naturally infected dogs when seropositive to FML but completely asymptomatic. The clinical signs of the experimentally infected, symptomatic dogs only disappeared after the complete vaccination. Protection was obtained in 3/5 animals that remained asymptomatic, IDR positive and parasite free, 1 year after infection. Furthermore, the asymptomatic, FML-vaccine treated dogs showed stable anti-FML IgG1 levels, increasing IgG2 levels and 79-95% of positive DTH response, during the whole experiment. Twenty-two months after complete vaccination, no obits due to visceral leishmaniasis were recorded and 90% of these dogs were still asymptomatic, healthy and parasite free. On the other hand, 37% (17/46 dogs) kala-azar obits were recorded in a control group that received no treatment during the same period, and that was FML-seropositive and asymtpomatic at the beginning of the assay. Our results indicate that the FML-vaccine was effective in the immunotherapy against visceral leishmaniasis of asymptomatic infected dogs. Normal proportions of CD4 and CD21 lymphocytes were detected in PBMC by FACS analysis, in dogs submitted to immunotherapy, suggesting their non-infectious condition. All animals showed as well significantly increased percents of CD8 lymphocytes as expected for Quillaja saponin (QuilA) vaccine treatments. PMID:15149782

  6. Ecological interactions of visceral leishmaniasis in the state of Bahia, Brazil

    Italo A Sherlock

    1996-12-01

    Full Text Available The laboratory and field observations summarized in this paper on visceral leishmaniasis ecology in the State of Bahia, Brazil are based on the author's observations over the past 35 years in a number of state's foci, public health records and literature citations. The disease is endemic with epidemic outbreaks occurring every ten years and its geographical distribution is expanding rapidly in the last years. Leishmania chagasi is the main ethiologic agent of the visceral leishmaniasis but Le. amazonensis s. lato was the only leishmania isolated by other authors from some visceral leishmaniasis human cases in the state. Lutzomyia longipalpis (with one or two spots on tergites III and IV and two sized different populations was epidemiologically incriminated as the main vector. It was found naturally infected with promastigotes, and it was infected with four species of leishmanias in the laboratory. Although the experimental transmission of Le. amazonensis by the bite of Lu. longipalpis to hamsters was performed, the author was not successful in transmitting Le. chagasi in the same way. The dog is the most important domestic source for infection of the vector, however it is not a primary reservoir. The opossum Didelphis albiventris was found naturally infected with Le. chagasi but its role as reservoir is unknown. Foxes and rodents were not found infected with leishmanias in Bahia.

  7. Performance of Alere™ immunochromathographic test for the diagnosis of canine visceral leishmaniasis.

    Souza Filho, Job Alves de; Barbosa, José Ronaldo; Figueiredo, Fabiano Borges; Mendes, Artur Augusto Velho; Silva, Shara Regina da; Coelho, George Luiz Lins Machado; Marcelino, Andreza Pain

    2016-07-30

    The diagnosis and control of canine visceral leishmaniasis (CVL) has fundamental importance in the control of human visceral leishmaniasis. In this context, the immunochromathographic test (ICT) has emerged as a valuable diagnostic tool. Currently, in Brazil, the algorithm for the diagnosis of CVL uses Dual Path Platform (DPP) ICT as a screening test and ELISA as a confirmatory test. However, the DPP(®) ICT has been facing a problem of insufficient production to meet the national demand. Here, the Alere™ canine visceral leishmaniasis ICT was tested with serum samples from 159 dogs, including symptomatic, asymptomatic and healthy dogs, characterized by DPP(®) ICT and ELISA (panel A), or ELISA and Indirect Immunofluorescence Assay (IFA) (panel B), and parasitological examination as gold standard. In this study, the Alere™ ICT obtained 0.974 sensitivity for panel A and 0.854 sensitivity for panel B. The specificity was 1.0 for both panels. Thus, the Alere™ ICT has potential to be used for the serological diagnosis of CVL. PMID:27369585

  8. Temperature-derived potential for the establishment of phlebotomine sandflies and visceral leishmaniasis in Germany

    Dominik Fischer

    2010-11-01

    Full Text Available Climate change is expected to manifest in the shift of organisms to regions where they were not present in the past, potentially entailing previously unseen biological risks. However, studies evaluating these future trends are scarce. Here, an important group of vectors (sandflies and the pathogen transmitted (Leishmania infantum complex causing the infectious disease visceral leishmaniasis is investigated, focussing on potential establishment in Germany during the 21st century. As the most important habitat factor, temperature requirements of pathogen and vector were derived from the literature and compared with recent climate records - provided by worldclim - and climate change scenarios. Climate data from the Regional Climate Model REMO were obtained and averaged over the time periods 2011- 2040, 2041-2070 and 2071-2100. Projected temperature changes (based on the A1B and A2 scenarios were correlated with the constraints of vector and pathogen. Simulated potentially suitable habitat areas for vector and pathogen were merged to generate a temperature-derived risk map of visceral leishmaniasis. Temperature conditions seem to become suitable for the vector across large swaths of Germany. Nevertheless, temperature constraints for the pathogen may defer the establishment of the parasitic disease, particularly during the first half of the 21st century. Long-lasting epidemics of visceral leishmaniasis are therefore not expected in Germany during the next few decades, although during extremely warm years an increase in autochthonous cases of leishmaniasis may occur. The southwest (Upper Rhine Valley and west (Cologne Bight of Germany are identified as risk areas. The time of potential establishment and corresponding rise in biological risk varies between scenarios, due to differences in the predicted rate of temperature increase.

  9. Evaluation of antileishmanial potential of Tinospora sinensis against experimental visceral leishmaniasis.

    Singh, Nasib; Kumar, Awanish; Gupta, Prasoon; Chand, Kailash; Samant, Mukesh; Maurya, Rakesh; Dube, Anuradha

    2008-02-01

    The chemotherapeutic interventions against visceral leishmaniasis (VL) are limited and facing serious concerns of toxicity, high cost, and emerging drug resistance. There is a greater interest in new drug developments from traditionally used medicinal plants which offers unprecedented diversity in structures and bioactivity. With this rationale, ethanolic extract of Tinospora sinensis Linn and its four fractions were tested in vitro against promastigotes and intracellular amastigotes and in vivo in Leishmania donovani infected hamsters. Ethanolic extract exhibited an appreciable activity against promastigotes (IC(50) 37.6+/-6.2 microg/ml) and intracellular amastigotes (IC(50) 29.8+/-3.4 microg/ml). In hamsters, it resulted in 76.2+/-9.2% inhibition at 500 mg/kg/day x 5 oral dose level. Among fractions, n-butanol imparted highest in vitro and in vivo activities. Ethanolic extract and butanol fraction also enhances reactive oxygen species (ROS) and nitric oxide (NO) release. The results indicate that T. sinensis may provide new lead molecules for the development of alternative drugs against VL. PMID:18080140

  10. Leishmania donovani: impairment of the cellular immune response against recombinant ornithine decarboxylase protein as a possible evasion strategy of Leishmania in visceral leishmaniasis.

    Yadav, Anupam; Amit, Ajay; Chaudhary, Rajesh; Chandel, Arvind Singh; Mahantesh, Vijay; Suman, Shashi Shekhar; Singh, Subhankar Kumar; Dikhit, Manas Ranjan; Ali, Vahab; Rabidas, Vidyanand; Pandey, Krishna; Kumar, Anil; Das, Pradeep; Bimal, Sanjiva

    2015-01-01

    Ornithine decarboxylase, the rate limiting enzyme of the polyamine biosynthesis pathway, is significant in the synthesis of trypanothione, T(SH)2, the major reduced thiol which is responsible for the modulation of the immune response and pathogenesis in visceral leishmaniasis. Data on the relationship between ornithine decarboxylase and the cellular immune response in VL patients are limited. Therefore, we purified a recombinant ornithine decarboxylase from Leishmania donovani (r-LdODC) of approximately 77kDa and examined its effects on the immunological responses in peripheral blood mononuclear cells of human visceral leishmaniasis cases. For these studies, α-difluoromethylornithine was tested as an inhibitor and was used in parallel in all experiments. The r-LdODC was identified as having a direct correlation with parasite growth and significantly increased the number of promastigotes as well as axenic amastigotes after 96h of culture. The stimulation of peripheral blood mononuclear cells with r-LdODC up-regulated IL-10 production but not IFN-γ production from CD4(+) T cells in active as well as cured visceral leishmaniasis cases, indicating a pivotal role for r-LdODC in causing strong immune suppression in a susceptible host. In addition, severe hindrance of the immune response and anti-leishmanial macrophage function due to r-LdODC, as revealed by decreased IL-12 and nitric oxide production, and down-regulation in mean fluorescence intensities of reactive oxygen species, occurred in visceral leishmaniasis patients. There was little impact of r-LdODC in the killing of L. donovani amastigotes in macrophages of visceral leishmaniasis patients. In contrast, when cultures of promastigotes and amastigotes, and patients' blood samples, were directed against α-difluoromethylornithine, parasite numbers significantly reduced in culture, whereas the levels of IFN-γ and IL-12, and the production of reactive oxygen species and nitric oxide, were significantly elevated

  11. Mannose-binding Lectin (MBL) as a susceptible host factor influencing Indian Visceral Leishmaniasis.

    Mishra, Anshuman; Antony, Justin S; Gai, Prabhanjan; Sundaravadivel, Pandarisamy; Van, Tong Hoang; Jha, Aditya Nath; Singh, Lalji; Velavan, Thirumalaisamy P; Thangaraj, Kumarasamy

    2015-12-01

    Visceral Leishmaniasis (VL), caused by Leishmania donovani is endemic in the Indian sub-continent. Mannose-binding Lectin (MBL) is a complement lectin protein that binds to the surface of Leishmania promastigotes and results in activation of the complement lectin cascade. We utilized samples of 218 VL patients and 215 healthy controls from an Indian population. MBL2 functional variants were genotyped and the circulating MBL serum levels were measured. MBL serum levels were elevated in patients compared to the healthy controls (adjusted P=0.007). The MBL2 promoter variants -78C/T and +4P/Q were significantly associated with relative protection to VL (-78C/T, OR=0.7, 95% CI=0.5-0.96, adjusted P=0.026 and +4P/Q, OR=0.66, 95% CI=0.48-0.9, adjusted P=0.012). MBL2*LYQA haplotypes occurred frequently among controls (OR=0.69, 95% CI=0.5-0.97, adjusted P=0.034). MBL recognizes Leishmania and plays a relative role in establishing L. donovani infection and subsequent disease progression. In conclusion, MBL2 functional variants were associated with VL. PMID:26297290

  12. The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis.

    Patterson, Stephen; Wyllie, Susan; Norval, Suzanne; Stojanovski, Laste; Simeons, Frederick Rc; Auer, Jennifer L; Osuna-Cabello, Maria; Read, Kevin D; Fairlamb, Alan H

    2016-01-01

    There is an urgent requirement for safe, oral and cost-effective drugs for the treatment of visceral leishmaniasis (VL). We report that delamanid (OPC-67683), an approved drug for multi-drug resistant tuberculosis, is a potent inhibitor of Leishmania donovani both in vitro and in vivo. Twice-daily oral dosing of delamanid at 30 mg kg(-1) for 5 days resulted in sterile cures in a mouse model of VL. Treatment with lower doses revealed a U-shaped (hormetic) dose-response curve with greater parasite suppression at 1 mg kg(-1) than at 3 mg kg(-1) (5 or 10 day dosing). Dosing delamanid for 10 days confirmed the hormetic dose-response and improved the efficacy at all doses investigated. Mechanistic studies reveal that delamanid is rapidly metabolised by parasites via an enzyme, distinct from the nitroreductase that activates fexinidazole. Delamanid has the potential to be repurposed as a much-needed oral therapy for VL. PMID:27215734

  13. The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis

    Patterson, Stephen; Wyllie, Susan; Norval, Suzanne; Stojanovski, Laste; Simeons, Frederick RC; Auer, Jennifer L; Osuna-Cabello, Maria; Read, Kevin D; Fairlamb, Alan H

    2016-01-01

    There is an urgent requirement for safe, oral and cost-effective drugs for the treatment of visceral leishmaniasis (VL). We report that delamanid (OPC-67683), an approved drug for multi-drug resistant tuberculosis, is a potent inhibitor of Leishmania donovani both in vitro and in vivo. Twice-daily oral dosing of delamanid at 30 mg kg-1 for 5 days resulted in sterile cures in a mouse model of VL. Treatment with lower doses revealed a U-shaped (hormetic) dose-response curve with greater parasite suppression at 1 mg kg-1 than at 3 mg kg-1 (5 or 10 day dosing). Dosing delamanid for 10 days confirmed the hormetic dose-response and improved the efficacy at all doses investigated. Mechanistic studies reveal that delamanid is rapidly metabolised by parasites via an enzyme, distinct from the nitroreductase that activates fexinidazole. Delamanid has the potential to be repurposed as a much-needed oral therapy for VL. DOI: http://dx.doi.org/10.7554/eLife.09744.001 PMID:27215734

  14. Estimation of under-reported visceral Leishmaniasis (Vl cases in Bihar: a Bayesian approach

    A Ranjan

    2013-12-01

    Full Text Available Background: Visceral leishmaniasis (VL is a major health problem in the state of Bihar and adjoining areas in India. In absence of any active surveillance mechanism for the disease, there seems to be gross under-reporting of VL cases. Objective: The objective of this study was to estimate extent of under-reporting of VL cases in Bihar using pooled analysis of published papers. Method: We calculated the pooled common ratio (RRMH based on three studies and combined it with a prior distribution of ratio using inverse-variance weighting method. Bayesian method was used to estimate the posterior distribution of the “under-reporting factor” (ratio of unreported to reported cases. Results: The posterior distribution of ratio of unreported to reported cases yielded a mean of 3.558, with 95% posterior limits of 2.81 and 4.50. Conclusion: Bayesian approach gives evidence to the fact that the total number of VL cases in the state may be nearly more than three times that of currently reported figures. 

  15. Visceral Leishmaniasis/HIV co-infection in northeast Brazil: evaluation of outcome

    Lara Gurgel Fernandes Távora

    2015-12-01

    Full Text Available ABSTRACT Since the beginning of the HIV burden, Visceral Leishmaniasis (VL/HIV co-infection has been diagnosed not only in areas where VL is endemic (Latin America, India, Asia, Southern Europe, but also in North America, were it is considered an opportunistic disease. Clinical presentation, diagnostic tests sensitivity and treatment response in this population differs from VL alone. OBJECTIVES: To evaluate factors related to an unfavorable outcome in patients with VL/HIV diagnosis in a reference center in northeast Brazil. METHODS: Co-infected patients, diagnosed from 2010 to 2012, were included. Data from medical records were collected until one year after VL treatment completion. RESULTS: Forty-two HIV-infected patients were included in the study. Anemia, leukopenia, and thrombocytopenia were present in 95%, 70.7%, and 63.4%, respectively. Mean T CD4+ (LTCD4 lymphocyte count was 183 cells/dL. Highly active antiretroviral therapy (HAART was being used by 54.7% of cases. A favorable outcome was seen in 71.4% of cases. Recurrence of VL occurred in nine patients and deaths were secondary to infectious complications (3/42 patients. Very low LTCD4 count (<100 cells/dL was the only independent variable associated with an unfavorable outcome in multivariate analysis (p = 0.03. CONCLUSION: Low LTCD4 count at presentation was associated with unfavorable outcome in VL/HIV patients.

  16. Non invasive diagnostic tools for visceral leishmaniasis: a comparison of the immunoserological tests DAT, rK26 and rK39

    G. Teran-Angel; V. Rodriguez; R. de Silva; O. Zerpa; H. Schallig; M. Ulrich; M. Cabrera

    2010-01-01

    Introduction. Human visceral leishmaniasis is a serious public health problem in endemic countries because of its high potential lethality, particularly in children. Rapid diagnosis is essential to early treatment and control of visceral leishmaniasis. Objective. The aim was to compare three serodia

  17. Implications of co-infection of Leptomonas in visceral leishmaniasis in India.

    Selvapandiyan, Angamuthu; Ahuja, Kavita; Puri, Niti; Krishnan, Anuja

    2015-12-01

    Protozoan parasites Leishmania donovani (family: Trypanosomatidae) cause fatal visceral leishmaniasis (VL) and the infection relapses in apparently cured population as post kala-azar dermal leishmaniasis (PKDL) in the Indian subcontinent. In recent years co-infection of another Trypanosomatid parasite Leptomonas with L. donovani during VL/PKDL in this region has become prominent. The observation of clinically lesser-known insect parasite, Leptomonas in leishmaniasis is intriguing to researchers. The presence of Leishmania look alike Leptomonas in the cultures of clinical isolates of Leishmania has been worrisome to those, who prefer to work with pure Leishmania cultures for drug and vaccine development or immune response studies. The exact implications of such a co-habitation, which might lead to a delay in the diagnostics of VL and elevate mortality, need a thorough investigation. Also whether Leptomonas is involved in leishmaniasis manifestation needs to be ascertained. Thus we are currently witnessing a new paradigm of a parasitic co-infection in VL/PKDL cases in India and this review outlines various opportunities for further research in understanding such emerging co-infection. PMID:26492813

  18. Spatial distribution of human and canine visceral leishmaniasis in Belo Horizonte, Minas Gerais State, Brasil, 1994-1997.

    Oliveira, C D; Assunção, R M; Reis, I A; Proietti, F A

    2001-01-01

    In this paper, we present spatial analysis of the association between all incidents cases of human Visceral Leishmaniasis and seropositive dogs, from 1994 to 1997 in Belo Horizonte, a large Brazilian city. We geocoded 158 human cases and 11,048 seropositive dogs and compared canine prevalence rates with Human Bayesian Incidence rates in the same areas. We also used Knox's test to evaluate the hypothesis of space-time clustering of human cases in the period. Additionally, we used Kernel's maps for seropositive dogs distribution and located the human cases in the resulting smooth maps. We concluded that human and dog rates are correlated. Also, the Visceral Leishmaniasis in Belo Horizonte spread quickly, but apart from the rates' magnitude, it has kept the same spatial pattern through time. We believe it is possible to use this technique to choose areas to implement control measures against Visceral Leishmaniasis in a more efficient way. PMID:11679897

  19. FIRST CASE OF AUTOCHTHONOUS HUMAN VISCERAL LEISHMANIASIS IN THE URBAN CENTER OF RIO DE JANEIRO: CASE REPORT

    Guilherme Almeida Rosa da Silva

    2014-01-01

    Full Text Available Visceral leishmaniasis is an anthropozoonosis that is caused by protozoa of the genus Leishmania, especially Leishmania (Leishmania infantum, and is transmitted to humans by the bite of sandflies of the genus Lutzomyia, such as Lutzomyia longipalpis. There are many reservoirs, including Canis familiaris. It is a chronic infectious disease with systemic involvement that is characterized by three phases: the initial period, the state period and the final period. The main symptoms are fever, malnutrition, hepatosplenomegaly, and pancytopenia. This article reports a case of a patient diagnosed with visceral leishmaniasis in the final period following autochthonous transmission in the urban area of Rio de Janeiro. The case reported here is considered by the Municipal Civil Defense and Health Surveillance of Rio de Janeiro to be the first instance of autochthonous visceral leishmaniasis in humans in the urban area of this city. The patient was discharged and is undergoing a follow-up at the outpatient clinic, demonstrating clinical improvement.

  20. Epidemiological Aspects of Visceral Leishmaniasis in Baft District, Kerman Province, Southeast of Iran

    H Mahmoudvand

    2011-03-01

    Full Text Available Background: Visceral leishmaniasis (kala-azar is an endemic disease in some areas of Iran. A cross- sectional study was conducted for sero-epidemiological survey of visceral leishmaniasis (VL in Baft district from Kerman Province, southeast of Iran.Methods: Blood samples were collected from children up to 12 years old and 10% of adult population from Baft villages with a multi-stage randomized cluster sampling. In addition, blood samples were collected from 30 domestic dogs from the same areas. All the collected blood sam­ples were tested by direct agglutination test (DAT for the detection of anti-Leishmania antibod­ies in both human and dog using the cut-off value of ≥1:3200 and ≥ 1:320, respectively. Parasitologi­cal, molecular, and pathological were performed on infected dogs. Chi-square and Fisher exact tests were used to compare sero-prevalence values.Results: From 1476 collected human serum samples, 23 (1.55% showed anti-Leishmania antibod­ies at titers of 1:800 and 1:1600 whereas 14 (0.95% showed anti-Leishmania infantum antibodies at titers of ≤ 1:3200. No statistically significant difference was found between male (1.18 % and female (0.69% sero-prevalence (P=0.330. Children of 5-8 years showed the high­est sero-prevalence rate (3.22%. Seven out of 30 domestic dogs (23% showed anti-Leishmania antibodies at titers ≤1:320. Leishmania infantum was identified in five infected dogs by nested - PCR assay.Conclusion: It seems that visceral leishmaniasis is being endemic in southern villages of Baft district, southeast of Iran.

  1. Cost-effectiveness analysis of combination therapies for visceral leishmaniasis in the Indian subcontinent.

    Filip Meheus

    Full Text Available BACKGROUND: Visceral leishmaniasis is a systemic parasitic disease that is fatal unless treated. We assessed the cost and cost-effectiveness of alternative strategies for the treatment of visceral leishmaniasis in the Indian subcontinent. In particular we examined whether combination therapies are a cost-effective alternative compared to monotherapies. METHODS AND FINDINGS: We assessed the cost-effectiveness of all possible mono- and combination therapies for the treatment of visceral leishmaniasis in the Indian subcontinent (India, Nepal and Bangladesh from a societal perspective using a decision analytical model based on a decision tree. Primary data collected in each country was combined with data from the literature and an expert poll (Delphi method. The cost per patient treated and average and incremental cost-effectiveness ratios expressed as cost per death averted were calculated. Extensive sensitivity analysis was done to evaluate the robustness of our estimations and conclusions. With a cost of US$92 per death averted, the combination miltefosine-paromomycin was the most cost-effective treatment strategy. The next best alternative was a combination of liposomal amphotericin B with paromomycin with an incremental cost-effectiveness of $652 per death averted. All other strategies were dominated with the exception of a single dose of 10mg per kg of liposomal amphotericin B. While strategies based on liposomal amphotericin B (AmBisome were found to be the most effective, its current drug cost of US$20 per vial resulted in a higher average cost-effectiveness. Sensitivity analysis showed the conclusion to be robust to variations in the input parameters over their plausible range. CONCLUSIONS: Combination treatments are a cost-effective alternative to current monotherapy for VL. Given their expected impact on the emergence of drug resistance, a switch to combination therapy should be considered once final results from clinical trials are

  2. Tre tilfaelde af visceral leishmaniasis: det ene hos en HIV-positiv mand

    Balslev, U; Jonsbo, F; Junge, Jette;

    1991-01-01

    Three cases of visceral leishmaniasis (kala-azar) are presented. One of these was in a 43-year-old patient with AIDS who was infected in Southern Spain. Another was in a man aged 25 years infected in West Africa. These cases are the first two adults to be reported in Denmark. The third case was an...... 18 month old previously healthy boy, infected in Southern Spain. The symptomtology, diagnosis and treatment of the disease are discussed and it is stressed that serological diagnostic tests have limited value in HIV positive patients....

  3. Prevalence and distribution of canine visceral leishmaniasis antibodies in dogs in Mosul City

    D.M.T. Jwher

    2012-01-01

    The purpose of the current study to investigate of visceral leishmaniasis antibodies in blood of dogs. One hundred and fifty six samples of blood of stray and domestic dog blood samples of different ages and sexes and from various regions of Mosul city were collected. The study began from July to August 2010. The area of the study (Mosul city) was divided geographically in to two main areas i.e. right and left coasts of Mosul city. Also, another subdivision was followed in which each major ar...

  4. Outbreak of canine visceral leishmaniasis in Barra Mansa, State of Rio de Janeiro

    Cintia Xavier de Mello

    2014-12-01

    Full Text Available Introduction In Brazil, visceral leishmaniasis (VL has spread to various regions. This study reports canine cases of VL in Barra Mansa, where human VL cases were recently reported. Methods Using the human index case, a canine survey was performed by dual-path platform immunochromatography and enzyme-linked immunosorbent assay. Seropositive animals were euthanized. Cultures were collected to detect Leishmania parasites. Results Serological tests detected 141 canine VL cases, and Leishmania chagasi were isolated from 82.2% animals. Conclusions Leishmania chagasi is in circulation in Barra Mansa. This study broadens information on the parasite's distribution in the State of Rio de Janeiro.

  5. Distinct antigen recognition pattern during zoonotic visceral leishmaniasis in humans and dogs.

    Goto, Yasuyuki; Howard, Randall F; Bhatia, Ajay; Trigo, Joelma; Nakatani, Maria; Netto, Eduardo M; Reed, Steven G

    2009-03-23

    Leishmania infantum is a causative agent of endemic zoonotic visceral leishmaniasis (VL) in regions of South America and the Mediterranean. Dogs are the major reservoirs for L. infantum in these regions, and control of disease in dogs could have a significant impact on human disease. Although dogs share many symptoms of VL with humans as a result of L. infantum infection, they also show some unique clinical manifestations, which are often a combination of visceral and cutaneous leishmaniasis, suggesting different mechanisms of disease development in dogs and humans. Here, we compare antibody responses of dogs and humans with VL to various defined leishmanial antigens. Parasite lysate and K39, the two most commonly used antigens for serodiagnosis of VL, detected the highest levels of antibodies in both humans and dogs with VL, whereas the recognition patterns of these antigens were distinct between the hosts. Among other defined antigens tested, LmSTI1 and CPB detected higher levels of antibodies in dogs and humans, respectively. These results indicate there is a difference between humans and dogs in antigen recognition patterns during VL. We infer that different strategies may need to be used in development of vaccines and diagnostics for humans and for dogs. In addition, we show a correlation between antibody titers to several antigens and severity of clinical symptoms during canine VL. PMID:19059724

  6. Age structure of owned dogs under compulsory culling in a visceral leishmaniasis endemic area.

    Bortoletto, Danielly Vieira; Utsunomiya, Yuri Tani; Perri, Silvia Helena Venturoli; Ferreira, Fernando; Nunes, Cáris Maroni

    2016-01-01

    The age structure of the dog population is essential for planning and evaluating control programs for zoonotic diseases. We analyzed data of an owned-dog census in order to characterize, for the first time, the structure of a dog population under compulsory culling in a visceral leishmaniasis endemic area (Panorama, São Paulo State, Brazil) that recorded a dog-culling rate of 28% in the year of the study. Data on 1,329 households and 1,671 owned dogs revealed an owned dog:human ratio of 1:7. The mean age of dogs was estimated at 1.73 years; the age pyramid indicated high birth and mortality rates at the first year of age with an estimated cumulative mortality of 78% at the third year of age and expected life span of 2.75 years. In spite of the high mortality, a growth projection simulation suggested that the population has potential to grow in a logarithmic scale over the years. The estimated parameters can be further applied in models to maximize the impact and minimize financial inputs of visceral leishmaniasis control measures. PMID:27598014

  7. VISCERAL LEISHMANIASIS IN PETROLINA, STATE OF PERNAMBUCO, BRAZIL, 2007-2013

    ARAUJO, Andreina de Carvalho; GONÇALVES, Nara Nagle Vieira Matos; DANTAS-TORRES, Filipe; FERREIRA, Fernando; HORTA, Mauricio Claudio

    2016-01-01

    Visceral leishmaniasis is a life-threatening disease of great public health relevance in Brazil. The municipality of Petrolina is an endemic area in the State of Pernambuco, Brazil. This study was designed to assess the recent expansion of VL in the municipality of Petrolina, Pernambuco. Patients data were obtained from the Brazilian National Information System for Notifiable Diseases (SINAN). A total of 111 records from 2007 to 2013 were investigated, of which 69 were residents in Petrolina. The disease has predominantly affected 1-4 year old children (34.8%). Most of the patients were males (59.4%). Co-infection with human immunodeficiency virus occurred in 14.5% of the cases. The criterion most frequently used was the clinical and epidemiological confirmation (59.4%), with clinical cure in 78.3% of cases and one fatal outcome. Visceral leishmaniasis is endemic in Petrolina with transmission levels varying from moderate to high. The present study has shown the precariousness of the use of diagnostic tests in primary healthcare units, and this misuse has interfered with the diagnosis and treatment of cases. PMID:27074323

  8. Determinants of Visceral Leishmaniasis: A Case-Control Study in Gedaref State, Sudan.

    Fabienne Nackers

    2015-11-01

    Full Text Available Improving knowledge on local determinants of visceral leishmaniasis (VL is crucial to guide the development of relevant control strategies. This study aimed to identify individual and household level determinants of primary VL in 24 highly endemic villages of Tabarak Allah hospital's catchment area, Gedaref State, Sudan.From September 2012 to July 2013, in an unmatched case-control design, 198 patients with primary VL were compared to 801 controls free of VL symptoms and with a negative VL rapid test. Using random spatial sampling, controls were selected with a distribution of age, sex and village of residence proportionate to the distribution of the target population. Data were collected using a structured questionnaire.Children and men were at higher risk of VL. Reporting VL patient(s in the household in the previous year was the strongest VL risk factor. In a multivariate analysis, VL risk increased with household size, sleep location (outside the yard, not in the farm, evening outdoor activities in the rainy season (playing, watching TV, radio listening, use of ground nut oil as animal repellent and of smoke of Acacia seyal as indoor repellent, presence of dogs in the yard at night, Acacia nilotica in the yard's immediate surroundings and of a forest at eye range. VL risk appeared to decrease with the use of drinking water sources other than the village water tank, a buffer distance from the adjacent house yard, and with the presence of animals other than dogs in the yard at night. In contrast with previous studies, housing factors, mosquito-net use, black cotton soil, ethnicity, socioeconomic index, presence of Balanites aegyptica and Azadirachta indica in the yard were not independent VL determinants.Although these results do not provide evidence of causality, they provide useful suggestions for guiding further intervention studies on VL preventive measures.

  9. Tinospora cordifolia as a protective and immunomodulatory agent in combination with cisplatin against murine visceral leishmaniasis.

    Sachdeva, Heena; Sehgal, Rakesh; Kaur, Sukhbir

    2014-02-01

    Effect of pure herb, Tinospora cordifolia was studied for its hepatoprotective, nephroprotective and immunomodulatory activity against high dose cisplatin treatment in Leishmania donovani infected BALB/c mice. Administration of cisplatin (5mg/kg b.wt. daily for 5 days, i.p.) reduced the parasite load in L. donovani infected BALB/c mice but produced damage in liver and kidney as manifested biochemically by an increase in serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum urea, serum creatinine and various electrolytes etc. These biochemical analyses were further supported by cisplatin induced morphological changes in kidney, liver and spleen. To combat this pure herb, T. cordifolia (100mg/kg b.wt. for 15 days daily) was used in combination with cisplatin in L. donovani infected BALB/c mice and it was found that all the aforementioned changes were effectively attenuated by T. cordifolia when administered in combination with cisplatin. Moreover, flow cytometric analysis of lymphocyte surface markers of T cells (CD3+, CD4+ and CD8+), NK1.1 and B cells (CD19) indicated prominent enhancement in proliferation and differentiation of lymphocytes. T. cordifolia in combination with cisplatin selectively induced Th1 type of immune response as depicted by enhanced levels of IFN-γ and IL-2 whereas Th2 specific cytokines IL-4 and IL-10 observed a moderate decline. Confirmation of Th1 polarization was further obtained from augmented levels of IgG2a over IgG1 and heightened DTH (delayed type hypersensitivity) response. Thus, our results suggest that treatment by T. cordifolia may be a critical remedy for the amelioration of adverse effects of cisplatin. Thus, this might serve as a novel combination against visceral leishmaniasis in future. PMID:24370645

  10. Severe visceral leishmaniasis in children: the relationship between cytokine patterns and clinical features

    Monica Elinor Alves Gama

    2013-12-01

    Full Text Available Introduction The relationship between severe clinical manifestations of visceral leishmaniasis (VL and immune response profiles has not yet been clarified, despite numerous studies on the subject. This study aimed to investigate the relationship between cytokine profiles and the presence of immunological markers associated with clinical manifestations and, particularly, signs of severity, as defined in a protocol drafted by the Ministry of Health (Brazil. Methods We conducted a prospective, descriptive study between May 2008 and December 2009. This study was based on an assessment of all pediatric patients with VL who were observed in a reference hospital in Maranhão. Results Among 27 children, 55.5% presented with more than one sign of severity or warning sign. Patients without signs of severity or warning signs and patients with only one warning sign had the highest interferon-gamma (IFN-γ levels, although their interleukin 10 (IL-10 levels were also elevated. In contrast, patients with the features of severe disease had the lowest IFN-γ levels. Three patients who presented with more than two signs of severe disease died; these patients had undetectable interleukin 2 (IL-2 and IFN-γ levels and low IL-10 levels, which varied between 0 and 36.8pg/mL. Conclusions Our results showed that disease severity was associated with low IFN-γ levels and elevated IL-10 levels. However, further studies with larger samples are needed to better characterize the relationship between disease severity and cytokine levels, with the aim of identifying immunological markers of active-disease severity.

  11. DDT-based indoor residual spraying suboptimal for visceral leishmaniasis elimination in India

    Coleman, Michael; Foster, Geraldine M.; Deb, Rinki; Pratap Singh, Rudra; Ismail, Hanafy M.; Shivam, Pushkar; Ghosh, Ayan Kumar; Dunkley, Sophie; Kumar, Vijay; Coleman, Marlize; Hemingway, Janet; Paine, Mark J. I.; Das, Pradeep

    2015-01-01

    Indoor residual spraying (IRS) is used to control visceral leishmaniasis (VL) in India, but it is poorly quality assured. Quality assurance was performed in eight VL endemic districts in Bihar State, India, in 2014. Residual dichlorodiphenyltrichloroethane (DDT) was sampled from walls using Bostik tape discs, and DDT concentrations [grams of active ingredient per square meter (g ai/m2)] were determined using HPLC. Pre-IRS surveys were performed in three districts, and post-IRS surveys were performed in eight districts. A 20% threshold above and below the target spray of 1.0 g ai/m2 was defined as “in range.” The entomological assessments were made in four districts in IRS and non-IRS villages. Vector densities were measured: pre-IRS and 1 and 3 mo post-IRS. Insecticide susceptibility to 4% DDT and 0.05% deltamethrin WHO-impregnated papers was determined with wild-caught sand flies. The majority (329 of 360, 91.3%) of pre-IRS samples had residual DDT concentrations of <0.1 g ai/m2. The mean residual concentration of DDT post-IRS was 0.37 g ai/m2; 84.9% of walls were undersprayed, 7.4% were sprayed in range, and 7.6% were oversprayed. The abundance of sand flies in IRS and non-IRS villages was significantly different at 1 mo post-IRS only. Sand flies were highly resistant to DDT but susceptible to deltamethrin. The Stockholm Convention, ratified by India in 2006, calls for the complete phasing out of DDT as soon as practical, with limited use in the interim where no viable IRS alternatives exist. Given the poor quality of the DDT-based IRS, ready availability of pyrethroids, and susceptibility profile of Indian sand flies, the continued use of DDT in this IRS program is questionable. PMID:26124110

  12. Imidazole-containing phthalazine derivatives inhibit Fe-SOD performance in Leishmania species and are active in vitro against visceral and mucosal leishmaniasis.

    Sánchez-Moreno, M; Gómez-Contreras, F; Navarro, P; Marín, C; Ramírez-Macías, I; Rosales, M J; Campayo, L; Cano, C; Sanz, A M; Yunta, M J R

    2015-07-01

    The in vitro leishmanicidal activity of a series of imidazole-containing phthalazine derivatives 1-4 was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, and their cytotoxicity on J774·2 macrophage cells was also measured. All compounds tested showed selectivity indexes higher than that of the reference drug glucantime for the three Leishmania species, and the less bulky monoalkylamino substituted derivatives 2 and 4 were clearly more effective than their bisalkylamino substituted counterparts 1 and 3. Both infection rate measures and ultrastructural alterations studies confirmed that 2 and 4 were highly leishmanicidal and induced extensive parasite cell damage. Modifications to the excretion products of parasites treated with 2 and 4 were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds 2 and 4 were potent inhibitors of iron superoxide dismutase enzyme (Fe-SOD) in the three species considered, whereas their impact on human CuZn-SOD was low. Molecular modelling suggests that 2 and 4 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the antioxidant features of the enzyme. PMID:25823476

  13. Disruption of Splenic Lymphoid Tissue and Plasmacytosis in Canine Visceral Leishmaniasis: Changes in Homing and Survival of Plasma Cells

    Silva-O’Hare, Joselli; de Oliveira, Isabela Silva; Klevorn, Thaís; Almeida, Valter A.; Oliveira, Geraldo G. S.; Atta, Ajax M.; de Freitas, Luiz Antonio R.; dos-Santos, Washington L. C.

    2016-01-01

    Visceral leishmaniasis (VL) is a disease caused by Leishmania infantum, which is transmitted by phlebotomine sandflies. Dogs are the main urban reservoir of this parasite and the disease presents similar characteristics in both humans and dogs. In this paper, we investigated the potential pathways involved in plasma cell replacement of normal cell populations in the spleen, with respect to disease severity in dogs from an endemic area for visceral leishmaniasis. To this end, canine spleen samples were grouped into three categories: TYPE1SC- (non-infected dogs or without active infection with organized white pulp), TYPE1SC+ (infected dogs with organized white pulp) or TYPE3SC+ (infected animals with disorganized white pulp). We analyzed the distribution of different plasma cell isotypes (IgA, IgG and IgM) in the spleen. The expression of cytokines and chemokines involved in plasma cell homing and survival were assessed by real time RT-PCR. Polyclonal B cell activation and hypergammaglobulinemia were also evaluated. The proportion of animals with moderate or intense plasmacytosis was higher in the TYPE3SC+ group than in the other groups (Fisher test, P<0.05). This was mainly due to a higher density of IgG+ plasma cells in the red pulp of this group. The albumin/globulin ratio was lower in the TYPE3SC+ animals than in the TYPE1SC- or TYPE1SC+ animals, which evidences VL-associated dysproteinemia. Interestingly, TYPE3SC+ animals showed increased expression of the BAFF and APRIL cytokines, as well as chemokine CXCL12. Aberrant expression of BAFF, APRIL and CXCL12, together with amplified extrafollicular B cell activation, lead to plasma cell homing and the extended survival of these cells in the splenic red pulp compartment. These changes in the distribution of immunocompetent cells in the spleen may contribute to the progression of VL, and impair the spleen’s ability to protect against blood borne pathogens. PMID:27243459

  14. Case Report: No Response to Liposomal Daunorubicin in a Patient with Drug-Resistant HIV-Associated Visceral Leishmaniasis.

    Nicholas J Gow

    Full Text Available Visceral leishmaniasis (VL in patients with HIV co-infection presents a significant therapeutic challenge due to the lessened chance of achieving long-term cure. We report a case of VL in a 60-year-old man with HIV infection who became refractory to anti-leishmania treatment due to multi-drug resistance. In the face of a worsening clinical situation, and with no other options available, he was treated with an experimental regimen of liposomal daunorubicin, which has previously been shown to have in vitro activity against Leishmania donovani and to be effective treatment of VL in animal studies. To our knowledge, he was the first patient with VL and HIV co-infection to have this treatment evaluated. We report on the lack of response to this treatment and possible causes for its failure.

  15. Leishmaniasis in beige mice.

    Kirkpatrick, C E; Farrell, J P

    1982-01-01

    The courses of two protozoal diseases, cutaneous and visceral leishmaniasis, were examined in three groups of C57BL/6J mice. One group of mice was homozygous recessive for the beige gene (bg/bg). Beige mice are the genetic homologue of the human Chédiak-Higashi syndrome and, among other defects, are profoundly deficient in natural killer cell activity. Wild-type (+/+) mice, which respond to experimental cutaneous or visceral leishmaniasis by eventually eliminating their parasites, and heteroz...

  16. Detection of leishmanial antigen in the urine of patients with visceral leishmaniasis by a latex agglutination test.

    Sundar, Shyam; Agrawal, Shrinkhla; Pai, Kalpana; Chance, Michael; Hommel, Marcel

    2005-08-01

    Diagnosis of visceral leishmaniasis (VL) is usually done by demonstration of parasites in tissue smears. However, obtaining these smears may be risky, painful, and difficult. Antibody-based diagnostics are limited by their inability to predict active disease. In this study, a new latex agglutination test (KAtex), which detects parasite antigen in freshly voided and boiled urine, was evaluated in patients with VL before the start (n = 382) and at the end of treatment (n = 273); 185 healthy controls from leishmaniasis-endemic region were also studied. The KAtex result was positive in 87% (95% confidence interval [CI] = 83.3-90.3). However, at the end of treatment only 3% (95% CI = 1.6-6.2) patients were positive. The specificity of the test was 99% and 2 of 185 healthy controls tested positive. Positive and negative predictive values were 0.994 and 0.788, respectively. KAtex is a promising test, and in a simplified and improved format it could be applied meaningfully in the diagnosis of VL. PMID:16103587

  17. Entomological survey of phlebotomine sand flies (Diptera: Psychodidae in a focus of visceral leishmaniasis in central Iran

    Mohammad Motovali Emami

    2008-02-01

    Full Text Available Background & objectives: Visceral leishmaniasis (VL is a major vector-borne disease in Iran. A focus of VL is present in Shahreza county, Isfahan province, central Iran. The main objective of this study was to determine the probable vectors in this area. Methods: Sand flies were collected biweekly using sticky paper traps, CDC light-traps, and aspirators from outdoors as well as indoors. All female sand flies were dissected and identified. Promastigotes were inoculated to hamsters and detected by Nested PCR. Approximately 7528 sand flies representing 12 species were collected from April 2003 to October 2004. Phlebotomus (Phlebotomus papatasi Scopoli, Phlebotomus (Larroussious major Annandale and Sergentomyia (Sergentomyia sintoni Pringle were the predominant species. Two percent of P. major was found with natural promastigote infections. Interpretation & conclusion: This is the first report of natural promastigote infection in P. major in central Iran. The activity of P. major started from April and ended in October with a peak in September. The parasites were identified as Leishmania infantum using standard PCR. P. major is a possible vector of leishmaniasis and is susceptible to DDT in this area.

  18. Immunodiagnosis of Canine Visceral Leishmaniasis Using Mimotope Peptides Selected from Phage Displayed Combinatorial Libraries

    Toledo-Machado, Christina Monerat; Machado de Avila, Ricardo Andrez; NGuyen, Christophe; Granier, Claude; Bueno, Lilian Lacerda; Carneiro, Claudia Martins; Menezes-Souza, Daniel; Carneiro, Rubens Antonio; Chávez-Olórtegui, Carlos; Fujiwara, Ricardo Toshio

    2015-01-01

    ELISA and RIFI are currently used for serodiagnosis of canine visceral leishmaniasis (CVL). The accuracy of these tests is controversial in endemic areas where canine infections by Trypanosoma cruzi may occur. We evaluated the usefulness of synthetic peptides that were selected through phage display technique in the serodiagnosis of CVL. Peptides were chosen based on their ability to bind to IgGs purified from infected dogs pooled sera. We selected three phage clones that reacted only with those IgGs. Peptides were synthesized, polymerized with glutaraldehyde, and used as antigens in ELISA assays. Each individual peptide or a mix of them was reactive with infected dogs serum. The assay was highly sensitive and specific when compared to soluble Leishmania antigen that showed cross-reactivity with anti-T. cruzi IgGs. Our results demonstrate that phage display technique is useful for selection of peptides that may represent valuable synthetic antigens for an improved serodiagnosis of CVL. PMID:25710003

  19. Canine antibody response to Lutzomyia longipalpis saliva in endemic area of visceral leishmaniasis.

    Luís Fábio da Silva Batista

    2016-06-01

    Full Text Available Abstract: INTRODUCTION: Canine exposure to Lutzomyia longipalpis bites and the potential of Leishmania infantum transmissibility for the vector were evaluated. METHODS Immunoglobulin G (IgG anti-Lu longipalpis saliva and -L. infantum, and blood parasite load were determined in dogs from endemic areas of visceral leishmaniasis. RESULTS Blood parasitism was similar between symptomatic and asymptomatic dogs. IgG anti-L. infantum was higher in symptomatic dogs, but IgG anti-Lu. longipalpis saliva was mostly observed in higher titers in asymptomatic dogs, indicating vector preference for feeding on asymptomatic dogs. CONCLUSIONS Our data suggest a pivotal role of asymptomatic dogs in L. infantum transmission in endemic areas.

  20. Immunogenicity and protective efficacy of DNA vaccine against visceral leishmaniasis in BALB/c mice

    Kaur, Sukhbir; Kaur, Tejinder; Joshi, Jyoti

    2016-01-01

    Abstract The current study was designed to examine the protective efficacy of DNA vaccines based on gp63 and Hsp70 against murine visceral leishmaniasis. Inbred BALB/c mice were immunized subcutaneously twice at an interval of three weeks with pcDNA3.1(+) encoding T cell epitopes of gp63 and Hsp70 individually and in combination. Animals were challenged intracardially with 107 promastigotes of Leishmania donovani 10 days post immunization and sacrificed 1, 2 and 3 months post challenge. The immunized animals revealed a significant reduction (P animals treated with a combination of pcDNA/gp63 and pcDNA/Hsp70. These animals also showed heightened DTH response, increased IgG2a, elevated Th1 cytokines (IFN-γ and IL-2) and reduced IgG1 and IL-10 levels. Thus, mice immunized with the cocktail vaccine exhibited significantly greater protection in comparison to those immunized with individual antigens.

  1. Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda.

    Guerin, Philippe J; Olliaro, Piero; Sundar, Shyam; Boelaert, Marleen; Croft, Simon L; Desjeux, Philippe; Wasunna, Monique K; Bryceson, Anthony D M

    2002-08-01

    Visceral leishmaniasis is common in less developed countries, with an estimated 500000 new cases each year. Because of the diversity of epidemiological situations, no single diagnosis, treatment, or control will be suitable for all. Control measures through case finding, treatment, and vector control are seldom used, even where they could be useful. There is a place for a vaccine, and new imaginative approaches are needed. HIV co-infection is changing the epidemiology and presents problems for diagnosis and case management. Field diagnosis is difficult; simpler, less invasive tests are needed. Current treatments require long courses and parenteral administration, and most are expensive. Resistance is making the mainstay of treatment, agents based on pentavalent antimony, useless in northeastern India, where disease incidence is highest. Second-line drugs (pentamidine and amphotericin B) are limited by toxicity and availability, and newer formulations of amphotericin B are not affordable. The first effective oral drug, miltefosine, has been licensed in India, but the development of other drugs in clinical phases (paromomycin and sitamaquine) is slow. No novel compound is in the pipeline. Drug combinations must be developed to prevent drug resistance. Despite these urgent needs, research and development has been neglected, because a disease that mainly affects the poor ranks as a low priority in the private sector, and the public sector currently struggles to undertake the development of drugs and diagnostics in the absence of adequate funds and infrastructure. This article reviews the current situation and perspectives for diagnosis, treatment, and control of visceral leishmaniasis, and lists some priorities for research and development. PMID:12150849

  2. Predicted Distribution of Visceral Leishmaniasis Vectors (Diptera: Psychodidae; Phlebotominae) in Iran: A Niche Model Study.

    Hanafi-Bojd, A A; Rassi, Y; Yaghoobi-Ershadi, M R; Haghdoost, A A; Akhavan, A A; Charrahy, Z; Karimi, A

    2015-12-01

    Visceral leishmaniasis (VL) is an important vector-borne disease in Iran. Till now, Leishmania infantum has been detected from five species of sand flies in the country including Phlebotomus kandelakii, Phlebotomus major s.l., Phlebotomus perfiliewi, Phlebotomus alexandri and Phlebotomus tobbi. Also, Phlebotomus keshishiani was found to be infected with Leishmania parasites. This study aimed at predicting the probable niches and distribution of vectors of visceral leishmaniasis in Iran. Data on spatial distribution studies of sand flies were obtained from Iranian database on sand flies. Sample points were included in data from faunistic studies on sand flies conducted during 1995-2013. MaxEnt software was used to predict the appropriate ecological niches for given species, using climatic and topographical data. Distribution maps were prepared and classified in ArcGIS to find main ecological niches of the vectors and hot spots for VL transmission in Iran. Phlebotomus kandelakii, Ph. major s.l. and Ph. alexandri seem to have played a more important role in VL transmission in Iran, so this study focuses on them. Representations of MaxEnt model for probability of distribution of the studied sand flies showed high contribution of climatological and topographical variables to predict the potential distribution of three vector species. Isothermality was found to be an environmental variable with the highest gain when used in isolation for Ph. kandelakii and Ph. major s.l., while for Ph. alexandri, the most effective variable was precipitation of the coldest quarter. The results of this study present the first prediction on distribution of sand fly vectors of VL in Iran. The predicted distributions were matched with the disease-endemic areas in the country, while it was found that there were some unaffected areas with the potential transmission. More comprehensive studies are recommended on the ecology and vector competence of VL vectors in the country. PMID:26032232

  3. Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis.

    Carrillo, E; Ahmed, S; Goldsmith-Pestana, K; Nieto, J; Osorio, Y; Travi, B; Moreno, J; McMahon-Pratt, D

    2007-02-01

    The P-8 proteoglycolipid complex (P-8 PGLC), an amastigote antigen of Leishmania pifanoi, has been demonstrated to induce protection in mouse models, as well as to induce Tc1/Th1-like cellular responses in American cutaneous leishmaniasis patients. Because the immunization with P-8 PGLC in the murine model does not appear to be genetically restricted, we have studied the reactivity of the P-8 PGLC in Leishmania infantum infected dogs. In this study, it is shown that PBMC from experimentally infected dogs (asymptomatic, oligosymptomatic) significantly proliferated in response to soluble leishmanial antigen (SLA) or the P-8 PGLC. Further, quantification of the gene expression induced by the stimulation with P-8 in asymptomatically infected dogs showed an up-regulation of IFN-gamma and TNF-alpha, which were three to 4-fold higher than that induced by soluble Leishmania antigen (SLA). While no measurable induction of IL-10 was observed, low levels of IL-4 mRNA were observed in response to both P-8 and SLA antigens. Thus, our studies establish that P-8 is recognized by infected canines and elicits a potentially curative/protective Th1-like immune response. The identification of Leishmania antigens that elicit appropriate immune responses across different host species (humans, canine) and disease manifestations (cutaneous or visceral) could be an advantage in generating a general vaccine for leishmaniasis. PMID:17178178

  4. Visceral Leishmaniasis Caused by Leishmania infantum in Salta, Argentina: Possible Reservoirs and Vectors.

    Barroso, Paola A; Marco, Jorge D; Locatelli, Fabricio M; Cardozo, Rubén M; Hoyos, Carlos L; Mora, María C; García Bustos, María F; López-Quiroga, Inés; Mimori, Tatsuyuki; Gentile, Alberto G; Barrio, Alejandra B; Korenaga, Masataka; Hashiguchi, Yoshihisha; Basombrío, Miguel A

    2015-08-01

    Cases of human visceral leishmaniasis (HVL) were not recorded until recently in the Chaco region of northwestern Argentina. Dogs were surveyed at the sites of infection of two HVL index cases in the Chaco region of Salta province. Canine cases (CanL) were diagnosed by two parasitological methods, two molecular methods targeting mini- and maxicircle DNA, and immunochromatographic dipstick. Among 77 dogs studied, 10 (13%) were found infected with Leishmania spp. In seven dogs and two humans, the infecting species was typed as Leishmania (Leishmania) infantum. The same genotype was detected in the human and two of the CanL. Although several diagnostic methods displayed weak or moderate agreement, the concordance values for serology versus maxicircle PCR were very good (Kappa index = 0.84). Sandflies captured in the area were identified as Lutzomyia migonei and Lu. cortelezzii/Lu. sallesi (cortelezzii complex). The focal appearance of leishmaniasis in dogs and humans in a sylvatic region and its relatively low prevalence of infection suggests that L. (L.) infantum transmission to dogs and humans may, in this region, stem from sylvatic reservoirs. PMID:26055744

  5. Application of Recombinant Proteins for Serodiagnosis of Visceral Leishmaniasis in Humans and Dogs.

    Farahmand, Mahin; Nahrevanian, Hossein

    2016-07-01

    Visceral leishmaniasis (VL) is a zoonotic disease caused by leishmania species. Dogs are considered to be the main reservoir of VL. A number of methods and antigen-based assays are used for the diagnosis of leishmaniasis. However, currently available methods are mainly based on direct examination of tissues for the presence of parasites, which is highly invasive. A variety of serological tests are commonly applied for VL diagnosis, including indirect fluorescence antibody test, enzyme-linked immunosorbent assay (ELISA), dot-ELISA, direct agglutination test, Western-blotting, and immunochromatographic test. However, when soluble antigens are used, serological tests are less specific due to cross-reactivity with other parasitic diseases. Several studies have attempted to replace soluble antigens with recombinant proteins to improve the sensitivity and the specificity of the immunodiagnostic tests. Major technological advances in recombinant antigens as reagents for the serological diagnosis of VL have led to high sensitivity and specificity of these serological tests. A great number of recombinant proteins have been shown to be effective for the diagnosis of leishmania infection in dogs, the major reservoir of L. infantum. Although few recombinant proteins with high efficacy provide reasonable results for the diagnosis of human and canine VL, more optimization is still needed for the appropriate antigens to provide high-throughput performance. This review aims to explore the application of different recombinant proteins for the serodiagnosis of VL in humans and dogs. PMID:26883952

  6. The rK39 immunochromatic dipstick testing: A study for K39 seroprevalence in dogs and human leishmaniasis patients for possible animal reservoir of cutaneous and visceral leishmaniasis in endemic focus of Satluj river valley of Himachal Pradesh (India)

    Sharma Nand; Mahajan Vikram; Negi Ajit; Verma Ghanshyam

    2009-01-01

    Background: The newly recognized endemic focus of leishmaniasis in Satluj river valley of Himachal Pradesh (India) has both localized cutaneous leishmaniasis (LCL) and visceral leishmaniasis (VL) predominantly caused by Leishmania donovani. Rapid rK39 immunochromatographic dipstick test detects circulating antibodies to recombinant K39 antigen of L. donovani-infantum complex and is highly specific/sensitive in diagnosing symptomatic or asymptomatic infection in humans and dogs. Methods: Th...

  7. Hoarseness as the Presenting Symptom of Visceral Leishmaniasis with Muco-Cutaneous Lesions: A Case Report.

    Hossein Mortazavi

    2015-06-01

    Full Text Available Herein, a 28-year-old man with hoarseness, skin and oral lesions is presented. At the time of admission, the patient had an erythematous plaque on his chin near his lower lip and an erythematous-violaceous plaque on his palate near the opening of the pharynx and 20 kg weight lost in last one year. The biopsy of his skin lesions by hematoxylin and eosin staining revealed an infiltration of the dermis by lymphoplasma and histiocytic cells with a loose granuloma formation suggestive of leishmaniasis. Biopsy of mucosal lesions revealed Leishman bodies in dermis. PCR was performed on the specimens of skin, bone marrow, mucosa, and saliva, the results were positive. The pathogenic agent was identified as Leishmania major by the nested PCR. Serologic tests including direct agglutination test (DAT and indirect immunofluorescence test (IFAT were positive with high titers of anti-L. infantum antibodies (1:102400 versus 1:800, respectively, indicative of visceral involvement. The patient responded to a combination of miltefosine and meglumine antimoniate (Glucantime®. Visceral involvement due to L. major is rarely reported. To the best of our knowledge, probably hoarseness due to L. major has not been previously reported from Iran.

  8. Citometria de fluxo no diagnóstico da leishmaniose visceral canina Flow cytometry used in canine visceral leishmaniasis diagnosis

    A.V. Carvalho Neta

    2006-08-01

    Full Text Available Descreve-se a padronização de nova metodologia para detecção de anticorpos antiformas promastigotas fixadas de L. (L. chagasi, por citometria de fluxo (AAPF-IgG, sua aplicabilidade e desempenho na identificação de casos de leishmaniose visceral canina (LVC. Foram avaliados dois grupos de cães classificados pela reação de imunofluorescência indireta (RIFI, como: não reatores (NR, n=10 e reatores (R, n=50 dos quais foram coletadas amostras de sangue (soro para realização dos testes laboratoriais. Os resultados relacionados ao estabelecimento, aplicabilidade e desempenho da metodologia AAPF-IgG demonstraram que essa metodologia possibilita a identificação de uma região de reatividade diferencial entre cães NR e R, no soro diluído a 1:2048 e o valor de 20% de parasitos fluorescentes positivos (PPFP como ponto de corte entre resultados positivos e negativos, mostrando que a AAPF-IgG aplica-se na identificação de casos de LVC, possibilitando distinguir 96% de cães R como positivos e 100% de cães NR como negativos. Esses resultados em conjunto sugerem que a utilização da AAPF-IgG pode ser um novo instrumento para ensaios clínicos de diagnóstico sorológico da LVC.The current study evaluated the standardization of a new methodology for detection of anti-fixed L. (L. chagasi promastigote antibodies by flow cytometry (AAPF-IgG, as well its applicability and performance in the identification of cases of Canine Visceral Leishmaniasis (CVL. Two groups of dogs were classified by RIFI (gold standard as no reactors (NR, n=10 and reactors (R, n=50. Blood samples were collected and used for the laboratorial tests (RIFI and AAPF-IgG. The results showed that the new AAPF-IgG assay makes possible the identification of an area of differential reactivity between dogs NR and R at the dilution of 1:2048 and 20% of percentage of positive fluorescent parasite as the cut point among positive and negative results. The AAPF-IgG assay was able to

  9. Visceral leishmaniasis in Rio de Janeiro, Brazil: eco-epidemiological aspects and control Leishmaniose visceral no Rio de Janeiro, Brasil: aspectos eco-epidemiológicos e controle

    Mauro Celio de Almeida Marzochi

    2009-10-01

    Full Text Available From 1977 (index case to 2006, 87 cases of visceral leishmaniasis were confirmed in the municipality of Rio de Janeiro, Brazil, in periurban areas on the continental and coastal slopes of the Pedra Branca massif and the continental slopes of the Gericinó massif. The majority (65.5% of the patients were more than five years old, predominantly males (61.5%, but without any difference between the sexes below the age of 14 years. The overall fatality rate was 10.4%. Two cases of visceral leishmaniasis/human immunodeficiency virus coinfection were detected. Leishmania chagasi was isolated from human and canine cases. The associations between the presence of phlebotomines and human and canine migrations, disorderly occupation involving degradation of environmental preservation areas and poor socioeconomic conditions may have created a favorable setting for the establishment and propagation of the disease. Close epidemiological surveillance associated with traditional control measures and others (active case researches, land clearing and health education, reduced the incidence of human cases from 2.8 per 100,000 inhabitants in 1981 to less than 0.01 per 100,000 since 1997. The canine infection rates decreased from 4.6% in 1984 to 1.6% in 2008. Lutzomyia longipalpis was not detected in some locations where human and canine cases occurred. In the years 2007 and 2008, no new human cases were reported, but there is a persistent and worrisome residual canine seroprevalence.Entre 1977 (caso índice e 2006 foram confirmados 87 casos de leishmaniose visceral no Município do Rio de Janeiro, oriundos de áreas peri-urbanas das vertentes continentais e litorâneas do Maciço da Pedra Branca e das vertentes continentais do Maciço do Gericinó. A maioria (65,5% dos pacientes tinha mais de 5 anos de idade, prevalecendo o sexo masculino (61,5%, sem diferença de freqüência entre os sexos até os 14 anos. A letalidade foi de 10,4%. Houve dois casos de co

  10. Relapse of visceral leishmaniasis in an HIV-infected patient successfully treated with a combination of miltefosine and amphotericin B.

    McQuarrie, Shauna; Kasper, Ken; Moffatt, Dana C; Marko, Daniel; Keynan, Yoav

    2015-01-01

    The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm(3), despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated. PMID:26744591

  11. Relapse of Visceral Leishmaniasis in an HIV-Infected Patient Successfully Treated with a Combination of Miltefosine and Amphotericin B

    Shauna McQuarrie

    2015-01-01

    Full Text Available The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm3, despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated.

  12. Relapse of Visceral Leishmaniasis in an HIV-Infected Patient Successfully Treated with a Combination of Miltefosine and Amphotericin B

    Shauna McQuarrie; Ken Kasper; Moffatt, Dana C; Daniel Marko; Yoav Keynan

    2015-01-01

    The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm3, despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigot...

  13. Low Sensitivity of Peripheral Blood Smear for Diagnosis of Subclinical Visceral Leishmaniasis in Human Immunodeficiency Virus Type 1-Infected Patients

    Delgado, J.; Pineda, J. A.; Macías, J.; Regordán, C.; Gallardo, J. A.; Leal, M.; Sanchez-Quijano, A.; Lissen, E.

    1998-01-01

    The peripheral blood smear is an easy method for the diagnosis of symptomatic visceral leishmaniasis (VL) in human immunodeficiency virus type 1 (HIV-1)-infected patients. However, its efficiency in diagnosing subclinical VL remains unknown. In this study, Leishmania amastigotes were seen in blood smears from 1 of 13 HIV-1-positive individuals with subclinical VL. This shows that this procedure is not suitable for subclinical-VL diagnosis.

  14. FIRST CASE OF AUTOCHTHONOUS HUMAN VISCERAL LEISHMANIASIS IN THE URBAN CENTER OF RIO DE JANEIRO: CASE REPORT

    Guilherme Almeida Rosa da Silva; Thiago de Oliveira Boechat; Fernando Raphael de Almeida Ferry; Jorge Francisco da Cunha Pinto; Marcelo Costa Velho Mendes de Azevedo; Ricardo de Souza Carvalho; Rogerio Neves Motta; Mariana Ferreira Veras

    2014-01-01

    Visceral leishmaniasis is an anthropozoonosis that is caused by protozoa of the genus Leishmania, especially Leishmania (Leishmania) infantum, and is transmitted to humans by the bite of sandflies of the genus Lutzomyia, such as Lutzomyia longipalpis. There are many reservoirs, including Canis familiaris. It is a chronic infectious disease with systemic involvement that is characterized by three phases: the initial period, the state period and the final period. The main symptoms are fever, ma...

  15. Larval Breeding Sites of Lutzomyia longipalpis (Diptera: Psychodidae) in Visceral Leishmaniasis Endemic Urban Areas in Southeastern Brazil

    Cláudio Casanova; Maria T M Andrighetti; Sampaio, Susy M. P.; Maria L G Marcoris; Fernanda E Colla-Jacques; Angelo P Prado

    2013-01-01

    BACKGROUND: The scarcity of information on the immature stages of sand flies and their preferred breeding sites has resulted in the focus of vectorial control on the adult stage using residual insecticide house-spraying. This strategy, along with the treatment of human cases and the euthanasia of infected dogs, has proven inefficient and visceral leishmaniasis continues to expand in Brazil. Identifying the breeding sites of sand flies is essential to the understanding of the vector's populati...

  16. Using Recombinant Proteins from Lutzomyia longipalpis Saliva to Estimate Human Vector Exposure in Visceral Leishmaniasis Endemic Areas

    Clarissa Teixeira; Regis Gomes; Nicolas Collin; David Reynoso; Ryan Jochim; Fabiano Oliveira; Amy Seitz; Dia-Eldin Elnaiem; Arlene Caldas; Ana Paula Souza; Cláudia I Brodskyn; Camila Indiani de Oliveira; Ivete Mendonca; Costa, Carlos H. N.; Petr Volf

    2010-01-01

    BACKGROUND: Sand flies deliver Leishmania parasites to a host alongside salivary molecules that affect infection outcomes. Though some proteins are immunogenic and have potential as markers of vector exposure, their identity and vector specificity remain elusive. METHODOLOGY/PRINCIPAL FINDINGS: We screened human, dog, and fox sera from endemic areas of visceral leishmaniasis to identify potential markers of specific exposure to saliva of Lutzomyia longipalpis. Human and dog sera were further ...

  17. Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review

    Boelaert, Marleen; Matlashewski, Greg; Mondal, Dinesh; Arana, Byron; Kroeger, Axel; Olliaro, Piero

    2016-01-01

    Background As Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission. Methodology/ Principal Finding We reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4–17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5–23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8–28.6% had no past history of VL treatment. The infectiveness of PKDL was 32–53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4–6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting. Conclusion/ Significance There is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection. PMID:27490264

  18. First comparative transcriptomic analysis of wild adult male and female Lutzomyia longipalpis, vector of visceral leishmaniasis.

    Christina B McCarthy

    Full Text Available Leishmaniasis is a vector-borne disease with a complex epidemiology and ecology. Visceral leishmaniasis (VL is its most severe clinical form as it results in death if not treated. In Latin America VL is caused by the protist parasite Leishmania infantum (syn. chagasi and transmitted by Lutzomyia longipalpis. This phlebotomine sand fly is only found in the New World, from Mexico to Argentina. However, due to deforestation, migration and urbanisation, among others, VL in Latin America is undergoing an evident geographic expansion as well as dramatic changes in its transmission patterns. In this context, the first VL outbreak was recently reported in Argentina, which has already caused 7 deaths and 83 reported cases. Insect vector transcriptomic analyses enable the identification of molecules involved in the insect's biology and vector-parasite interaction. Previous studies on laboratory reared Lu. longipalpis have provided a descriptive repertoire of gene expression in the whole insect, midgut, salivary gland and male reproductive organs. Nevertheless, the study of wild specimens would contribute a unique insight into the development of novel bioinsecticides. Given the recent VL outbreak in Argentina and the compelling need to develop appropriate control strategies, this study focused on wild male and female Lu. longipalpis from an Argentine endemic (Posadas, Misiones and a Brazilian non-endemic (Lapinha Cave, Minas Gerais VL location. In this study, total RNA was extracted from the sand flies, submitted to sequence independent amplification and high-throughput pyrosequencing. This is the first time an unbiased and comprehensive transcriptomic approach has been used to analyse an infectious disease vector in its natural environment. Transcripts identified in the sand flies showed characteristic profiles which correlated with the environment of origin and with taxa previously identified in these same specimens. Among these, various genes

  19. Spatial correlations of population and ecological factors with distribution of visceral leishmaniasis cases in southwestern Iran

    Mohammad Amin Ghatee

    2013-08-01

    Full Text Available Background & objectives: Leishmaniasis as a dynamic disease may be markedly influenced by demographic and ecological factors. A geospatial information system study was developed to determine the distribution of visceral leishmaniasis (VL cases in relation to population, climatic and environmental factors in Fars province, southwest of Iran. Methods: The dwelling addresses of 217 VL patients were obtained from hospital files. A hazard map produced by unifying buffers (5 km around nomads travel routes (NTR was developed to survey the effect of close proximity to NTR on the distribution of VL. Mean annual rainfall (MAR, mean annual temperature (MAT, four months temperature mean (T4, elevation, slope and landcover were climatic and environmental factors that have been analysed. Finally, data of dwelling foci were extracted from maps and analysed using logistic regression models. Results: Close proximity to NTR was the most important factor influenced on the disease distribution. Climatic factors were in second rank. Among them, temperature especially T4 is the most effective variable and rainfall was also shown to be another effective climatic agent. Most cases of VL were reported from temperate and semiarid areas in western and central regions while arid condition was a confined factor. The environmental factor of landcovers including urban, dry farm and thin forest regions was revealed as the third rank effective factor. Altitude importance was only shown when its effect was studied independently from other factors. Interpretation & conclusion: These findings present the distribution of VL in Fars province is influenced by combination of ecological and nomads demographical variables although closeness to NTR and nomads role in distribution and continuance of kala-azar are the most important factors.

  20. Cutaneous and post kala-azar dermal leishmaniasis caused by Leishmania infantum in endemic areas of visceral leishmaniasis, northwestern Iran 2002–2011: a case series

    Badirzadeh, Alireza; Mohebali, Mehdi; Ghasemian, Mehrdad; Amini, Hassan; Zarei, Zabiholah; Akhoundi, Behnaz; Hajjaran, Homa; Emdadi, Dariush; Molaei, Soheila; Kusha, Ahmad; Alizadeh, Saber

    2013-01-01

    Visceral leishmaniasis (VL) is endemic in Northwest and southern Iran. Reports of cutaneous leishmaniasis (CL) in Northwest areas are rare, and its etiological agents are unknown. In the current study, we report six CL and two post kala-azar dermal leishmaniasis (PKDL) cases caused by Leishmania infantum from endemic areas of VL in the Northwest. Smears were made from skin lesions of 30 suspected patients in 2002–2011, and CL was determined by microscopy or culture. Leishmania spp. were identified by nested-PCR assay. The disease was confirmed in 20 out of 30 (66%) suspected patients by parasitological examinations. L. infantum was identified in eight and Leishmania major in 12 CL cases by nested-PCR. Cutaneous leishmaniasis patients infected with L. major had the history of travel to CL endemic areas. L. infantum antibodies were detected by direct agglutination test (DAT) at titers of 1:3200 in two cases with history of VL. Results of this study indicated that L. infantum is a causative agent of CL as well as PKDL in the VL endemic areas. PMID:23816511

  1. PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis.

    Chiku, Vanessa Marim; Silva, Kathlenn Liezbeth Oliveira; de Almeida, Breno Fernando Martins; Venturin, Gabriela Lovizutto; Leal, Aline Aparecida Correa; de Martini, Cleber Costa; de Rezende Eugênio, Flavia; Dos Santos, Paulo Sergio Patto; de Lima, Valéria Marçal Felix

    2016-08-01

    Dogs infected with Leishmania infantum have a reduced number of T lymphocytes. PD-1 (Programmed cell death 1) a new member of the B7-CD28 family that is expressed by immune cells, and its binding to PD-L1 (CD274) or PD-L2 (CD273) induces the deactivation or apoptosis of T cells. This study aimed to evaluate the expression of PD-1 and its ligands, as well as blocking in the induction of apoptosis in T lymphocytes, TNF-α, IL-4 and nitric oxide production by leucokocytes from PBMC and spleen and the parasite load in dogs with visceral leishmaniasis (VL). Our results showed that the expression of PD1 and its ligands was increased in CD3(+) T cells and CD21(+) B lymphocytes within the peripheral blood and splenic mononuclear cells of dogs with VL. In peripheral blood monocytes, only PD-1 ligands exhibited increased expression; however, in spleen macrophages, increased expression of both PD-1 and its ligands was observed. Levels of apoptosis in peripheral blood and splenic T lymphocytes were higher in dogs with VL compared to healthy dogs. Blocking monoclonal antibodies to PD-1 and its ligands in the culture of mononuclear cells from the peripheral blood and spleen decreased the amount of CD3(+) T lymphocyte apoptosis. The concentration of nitric oxide, TNF-α and IL-4 increased in the culture supernatants of peripheral blood mononuclear cells treated with a blocking monoclonal antibody against PD-1. The TNF-α concentration increased in the culture supernatants of splenic cells following all treatments with antibodies blocking PD-1 and its ligands; however, the amount of IL-4 increased only in the presence of a PD-1 blocking agent. Treatment with a PD-1 blocking monoclonal antibody in the mononuclear peripheral blood of dogs with VL reduced the parasite burden while increased TNF-α. We conclude that in canine visceral leishmaniasis, PD-1 and its ligands are involved in the induction of T lymphocyte apoptosis and in regulating the production of nitric oxide, TNF

  2. Isolated mucosal Leishmaniasis

    Deepak Sundriyal; Naveen Kumar; Raj Kumar; Brijesh Sharma

    2013-01-01

    Leishmaniasis is a term used to define a group of clinical syndrome caused by various species of parasite Leishmania. Three main clinical types of leishmaniasis are visceral leishmaniasis, cutaneous leishmaniasis and mucocutaneous leishmaniasis. However, isolated presentation as mucosal disease is rare. We report a case of primarily mucosal leishmaniasis.

  3. Repeated training of accredited social health activists (ASHAs) for improved detection of visceral leishmaniasis cases in Bihar, India.

    Das, Vidya Nand Ravi; Pandey, Ravindra Nath; Kumar, Vijay; Pandey, Krishna; Siddiqui, Niyamat Ali; Verma, Rakesh Bihari; Matlashewski, Greg; Das, Pradeep

    2016-02-01

    Accredited Social Health Activists (ASHAs) are incentive-based, female health workers responsible for a village of 1000 population and living in the same community and render valuable services towards maternal and child health care, polio elimination program and other health care-related activities including visceral leishmaniasis (VL). One of the major health concerns is that cases remain in the endemic villages for weeks without treatment causing increased likelihood to treatment failure and disease transmission in the community. To address this problem, we have begun a training program for ASHAs to enhance early detection of potential VL cases and referring them to their local Primary Health Centers (PHCs) for diagnosis and treatment. The result of this training showed increased referral rate to PHCs for diagnosis and treatment. Encouraged with the results from a single training session, we determined in the present study whether repeated training of ASHAs resulted in an a further increase in VL case referral to the local PHCs. After two training sessions, VL referrals by ASHAs increased to 46% as compared to 28% after a single training session in this cohort and a baseline of 7% before training. ASHA training is an effective way to conduct active case detection of VL cases and should be repeated once a year. PMID:27077313

  4. VFV as a New Effective CYP51 Structure-Derived Drug Candidate for Chagas Disease and Visceral Leishmaniasis.

    Lepesheva, Galina I; Hargrove, Tatiana Y; Rachakonda, Girish; Wawrzak, Zdzislaw; Pomel, Sébastien; Cojean, Sandrine; Nde, Pius N; Nes, W David; Locuson, Charles W; Calcutt, M Wade; Waterman, Michael R; Daniels, J Scott; Loiseau, Philippe M; Villalta, Fernando

    2015-11-01

    Sterol 14α-demethylases (CYP51) are the enzymes essential for sterol biosynthesis. They serve as clinical targets for antifungal azoles and are considered as targets for treatment of human Trypanosomatidae infections. Recently, we have shown that VNI, a potent and selective inhibitor of trypanosomal CYP51 that we identified and structurally characterized in complex with the enzyme, can cure the acute and chronic forms of Chagas disease. The purpose of this work was to apply the CYP51 structure/function for further development of the VNI scaffold. As anticipated, VFV (R)-N-(1-(3,4'-difluorobiphenyl-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide, the derivative designed to fill the deepest portion of the CYP51 substrate-binding cavity, reveals a broader antiprotozoan spectrum of action. It has stronger antiparasitic activity in cellular experiments, cures the experimental Chagas disease with 100% efficacy, and suppresses visceral leishmaniasis by 89% (vs 60% for VNI). Oral bioavailability, low off-target activity, favorable pharmacokinetics and tissue distribution characterize VFV as a promising new drug candidate. PMID:25883390

  5. Visceral Leishmaniasis: A Differential Diagnosis to Remember after Bone Marrow Transplantation

    Margarida Dantas Brito

    2014-01-01

    Full Text Available Leishmania infection in immunocompromised hosts is reported in the literature, mostly concerning human immunodeficiency virus infected patients. It is not well characterized in the context of stem cell transplantation. We report a rare case clinical case of visceral leishmaniasis after allogeneic bone marrow transplantation. A 50-year-old Caucasian male was referred to allogeneic bone marrow transplantation with a high-risk acute lymphoblastic B leukemia in first complete remission. Allogeneic SCT was performed with peripheral blood stem cells from an unrelated Portuguese matched donor. In the following months, patient developed mild fluctuating cytopenias, mostly thrombocytopenia (between 60 and 80∗109/L. The only significant complaint was intermittent tiredness. The common causes for thrombocytopenia in this setting were excluded—no evidence of graft versus host disease, no signs of viral or bacterial infection, and no signs of relapsed disease/dysplastic changes. The bone marrow smear performed 12 months after transplantation revealed an unsuspected diagnosis: a massive bone marrow infiltration with amastigotes.

  6. [Visceral leishmaniasis in Argentina. Cases notification and distribution of vectors (2006-2012)].

    Gould, Ignacio T; Perner, Mónica S; Santini, María S; Saavedra, Silvina B; Bezzi, Gisella; Maglianese, Mariana I; Antman, Julián G; Gutiérrez, Jorge A; Salomón, Oscar D

    2013-01-01

    Visceral leishmaniasis (VL) is a notifiable disease in Argentina. Every new case diagnosed must be reported to the National Health Surveillance System. In the period 2006-2012, a total of 103 cases have been notified in four provinces: Entre Rios, Santa Fe, Misiones and Santiago del Estero. Misiones has the largest amount of cases: a total of 80, detected in 15 towns from May 2006 to July 2012. The highest incidence is observed in children (less than 15 years of age). In 2004 the vector Lutzomyia longipalpis was detected for the first time in Formosa Province. Cases of human and canine VL, as well as the presence of the canine vector were reported in 2006 in the province of Misiones, and in 2008-2009 in the province of Corrientes. In Santiago del Estero cases of human and canine VL (2008) were possibly associated with secondary vectors. In 2010 Lu longipalpis was found in Entre Rios, showing its dispersal to the south. Between January and April 2011 a systematic search of the VL vector was carried out in 13 towns, in Entre Ríos, Santa Fe and Santiago del Estero Provinces (275 traps/night). The colonization of the vector Lu longipalpis was proved in Chajarí town (Entre Rios), but not in Santiago del Estero Province, where Migonemyia migonei appears as a putative LV vector. PMID:23570757

  7. Comparison of clinical samples for visceral Leishmaniasis diagnosis in asymptomatic dogs by PCR hybridization

    The canine visceral leishmaniasis (CVL) diagnosis still represents a challenge because of complexity of this disease. The aim of present study was to compare different clinical samples for diagnosis of CVL by Polymerase Chain Reaction (PCR) combined with hybridization of 32P labeled probes. Bone marrow (BM), skin biopsy (SB), peripheral blood (PB) and conjunctival swab (CS) were used in this work. With this purpose 40 asymptomatic dogs, all positive by parasitological test, were obtained. From each animal were collected SB with sterile punches from ear internal surface, 1.0 mL of PB, BM aspirates from sternum and CS from both lower eyelid. Each clinical sample was submitted to suitable DNA purification process and PCR-hybridization assays. The positive results obtained with PCR were 55%, 25%, 30% and 22.5% for CS, BM, SB and PB respectively while the PCR followed by hybridization showed a positivity of 87.5%, 50%, 45% and 27.5% respectively. The hybridization assay was able to increase the PCR positivity in all kinds of clinical samples. The best performance was obtained using CS samples. We concluded that the PCR associated with DNA radioactive probes was a very sensitive tool for diagnosis of CVL in asymptomatic dogs and the CS has an important potential for regular screening of dogs. (author)

  8. Canine visceral leishmaniasis in kerman, southeast of iran: a seroepidemiological, histopathological and molecular study.

    Mehdi Bamorovat

    2014-09-01

    Full Text Available Canine visceral leishmaniasis (CVL is a systemic disease with a high mortality rate, caused by a diphasic protozoan parasite, Leishmania infantum/chagasi in the world. The objective of the present study was to determine the presence of CVL in the city and suburbs of Kerman, using a range of serological, histopathological and molecular methods.Blood samples were taken from 80 clinically symptomatic stray dogs All the collected blood samples were tested by direct agglutination test (DAT to detect the anti-Leishmania antibodies in dogs, using a cut-off value of ≥1:320. Pathological specimens including spleen, liver and lymph nodes were prepared for paraffin blocks, sectioning, staining and final microscopic examination in the pathology laboratory. PCR amplification of kDNA from 9 samples of DAT positive stray dogs was studied.The anti-Leishmania antibody was detected in 9 dogs (11.25 % of the total 80 studied dogs. No significant difference was found between VL infection and gender. In contrast, there was a significant difference between seropositivity and age (P<0.05. Pathological samples showed changes including hyperplasia of infected macrophages and inflammatory cells that occupied sinusoids and splenic cords. Among the samples which was characterized by PCR, only one specimen revealed to be mixed infection between L. infantum and L. tropica.The results revealed a high prevalence of L. infantum infection in stray dogs in Kerman. This kind of information is needed for implementation of future control programs.

  9. IL-18 gene polymorphism in patients with visceral leishmaniasis in East Azarbaijan, Iran.

    Ahmadpour, Ehsan; Bazmani, Ahad; Kohansal, Mohamad Hasan; Kazemi, Abdolhasan; Babaloo, Zohre

    2016-09-01

    Visceral leishmaniasis (VL) is a parasitic disease caused by Leishmania species. According to the important role of cellular immunity against VL, this study was directed to determine the frequency of -607A/C and -137G/C genotypes on promoter region of interleukin-18 gene. The study groups included 91 patients with confirmed history of VL, 106 healthy seronegative, and 79 healthy seropositive individuals. All three groups were analyzed by amplification refractory mutation system polymerase chain reaction (ARMS-PCR). The highest rate of -607/A, and -607/C alleles was observed in seronegative individuals (66/67 %) and in the patients (72/83 %). Allele frequency of -607/C is more than -607/A allele in all groups. In position of -137, frequency of -137/G allele in all groups was more than -137/C. Statistical analysis of distribution of genotypes, did not reveal any significant difference among groups. On the basis of the results, there was no significant association between VL and polymorphism of IL-18 promoter. The results of this study showed that IL-18 gene promoter polymorphisms at positions -607 and -137 are not associated with VL in East Azerbaijan, Iran. PMID:27605823

  10. Strategic evaluation of vaccine candidate antigens for the prevention of Visceral Leishmaniasis.

    Duthie, Malcolm S; Favila, Michelle; Hofmeyer, Kimberley A; Tutterrow, Yeung L; Reed, Steven J; Laurance, John D; Picone, Alessandro; Guderian, Jeffrey; Bailor, H Remy; Vallur, Aarthy C; Liang, Hong; Mohamath, Raodoh; Vergara, Julie; Howard, Randall F; Coler, Rhea N; Reed, Steven G

    2016-05-27

    Infection with Leishmania parasites results in a range of clinical manifestations and outcomes, the most severe of which is visceral leishmaniasis (VL). Vaccination will likely provide the most effective long-term control strategy, as the large number of vectors and potential infectious reservoirs renders sustained interruption of Leishmania parasite transmission extremely difficult. Selection of the best vaccine is complicated because, although several vaccine antigen candidates have been proposed, they have emerged following production in different platforms. To consolidate the information that has been generated into a single vaccine platform, we expressed seven candidates as recombinant proteins in E. coli. After verifying that each recombinant protein could be recognized by VL patients, we evaluated their protective efficacy against experimental L. donovani infection of mice. Administration in formulation with the Th1-potentiating adjuvant GLA-SE indicated that each antigen could elicit antigen-specific Th1 responses that were protective. Considering the ability to reduce parasite burden along with additional factors such as sequence identity across Leishmania species, we then generated a chimeric fusion protein comprising a combination of the 8E, p21 and SMT proteins. This E. coli -expressed fusion protein was also demonstrated to protect against L. donovani infection. These data indicate a novel recombinant vaccine antigen with the potential for use in VL control programs. PMID:27142329

  11. Impact of canine control on the epidemiology of canine and human visceral leishmaniasis in Brazil.

    Palatnik-de-Sousa, C B; dos Santos, W R; França-Silva, J C; da Costa, R T; Reis, A B; Palatnik, M; Mayrink, W; Genaro, O

    2001-11-01

    Brazil is the only country endemic for zoonotic visceral leishmaniasis (ZVL) that regularly conducts epidemiologic and prophylactic control programs that involve the treatment of human cases, insect vector control, and the removal of seropositive infected dogs. This report reviews 60 studies reporting data on the efficacy of these recommended control tools and concludes that in Brazil 1) eradication of the disease in Minas Gerais was achieved by the concomitant use of the three control methods, 2) although seropositivity by an immunofluorescent assay is not completely related to infectiousness, the removal of seropositive dogs leads to a significant reduction of canine and human incidence, 3) improvement of the sensitivity of the diagnostic tool used for canine control should optimize the efficacy of control, and 4) although difficult and expensive, the public health dog control campaigns performed in Brazil reduced the incidence of ZVL and should be maintained since treatment of dogs is an unrealistic intervention, both because of its prohibitive cost and relatively poor effectiveness. PMID:11716106

  12. Canine visceral leishmaniasis in Barra de Guaratiba, Rio de Janeiro, Brazil: assessment of risk factors

    Cabrera Maria Alice A.

    2003-01-01

    Full Text Available Barra de Guaratiba is a coastal area of the city of Rio de Janeiro where American visceral leishmaniasis (AVL is endemic. Although control measures including killing of dogs and use of insecticides have been applied at this locality, the canine seroprevalence remains at 25% and during 1995 and 1997 eight autochthonous human cases were notified. In order to evaluate factors related to the increase of the risk for Leishmania (Leishmania chagasi infection in dogs we have screened 365 dogs by anti-Leishmania immunofluorescent antibody test (IFAT and captured sandflies in the domestic and peridomestic environment. Some variables related to the infection were assessed by uni- and multivariate analysis. The distance of the residence from the forest border, its altitude and the presence of the opossum Didelphis marsupialis in the backyard, were found predictor factors for L. (L. chagasi infection in dogs in Barra de Guaratiba. The presence of Lutzomyia longipalpis in the peridomestic environment indicates the possibility of appearence of new human cases. Our data also suggest the presence of a sylvatic enzootic cycle at this locality.

  13. Canine visceral leishmaniasis in Barra de Guaratiba, Rio de Janeiro, Brazil: assessment of risk factors.

    Cabrera, Maria Alice A; Paula, Adelzon A; Camacho, Luis Antonio B; Marzochi, Mauro Célio A; Xavier, Samanta C; da Silva, Alba Valéria M; Jansen, Ana Maria

    2003-01-01

    Barra de Guaratiba is a coastal area of the city of Rio de Janeiro where American visceral leishmaniasis (AVL) is endemic. Although control measures including killing of dogs and use of insecticides have been applied at this locality, the canine seroprevalence remains at 25% and during 1995 and 1997 eight autochthonous human cases were notified. In order to evaluate factors related to the increase of the risk for Leishmania (Leishmania) chagasi infection in dogs we have screened 365 dogs by anti-Leishmania immunofluorescent antibody test (IFAT) and captured sandflies in the domestic and peridomestic environment. Some variables related to the infection were assessed by uni- and multivariate analysis. The distance of the residence from the forest border, its altitude and the presence of the opossum Didelphis marsupialis in the backyard, were found predictor factors for L. (L.) chagasi infection in dogs in Barra de Guaratiba. The presence of Lutzomyia longipalpis in the peridomestic environment indicates the possibility of appearence of new human cases. Our data also suggest the presence of a sylvatic enzootic cycle at this locality. PMID:12754572

  14. Predictors of an unsatisfactory response to pentavalent antimony in the treatment of American visceral leishmaniasis

    Santos Mácia A.

    2002-01-01

    Full Text Available Although treatment of visceral leishmaniasis with pentavalent antimony is usually successful, some patients require second-line drug therapy, most commonly with amphotericin B. To identify the clinical characteristics that predict an inadequate response to pentavalent antimony, a case-control study was undertaken in Teresina, Piaui, Brazil. Over a two-year period, there were 19 cases of VL in which the staff physicians of a hospital prescribed second-line therapy with amphotericin B after determining that treatment with pentavalent antimony had failed. The control group consisted of 97 patients that were successfully treated with pentavalent antimony. A chart review using univariate and multivariate analysis was performed. The cure rate was 90% with amphotericin B. The odds ratio for the prescription of amphotericin B was 10.2 for children less than one year old, compared with individuals aged over 10 years. Patients who presented coinfection had an OR of 7.1 while those on antibiotics had an OR of 2.8. These data support either undertaking a longer course of therapy with pentavalent antimony for children or using amphotericin B as a first-line agent for children and individuals with coinfections. It also suggests that chemoprophylaxis directed toward bacterial coinfection in small children with VL may be indicated.

  15. Larval microhabitats of Lutzomyia longipalpis (Diptera: Psychodidae) in an endemic focus of visceral leishmaniasis in Colombia.

    Ferro, C; Pardo, R; Torres, M; Morrison, A C

    1997-11-01

    An intensive search for the larval habitats of Lutzomyia longipalpis (Lutz & Neiva) was conducted from November 1992 to October 1993 at a small rural community in Colombia where American visceral leishmaniasis is endemic. Emergence traps constructed from polyvinyl chloride pipes were used to sample a variety of soil microhabitats that included edge areas of covered pigpens, cattle corrals, the base of trees, and leaf litter at sites within 40 m of a house, rocks in fields located between 50 and 500 m from houses, and sites within a patch of secondary forest (rocks, base of palm trees, and leaf litter). The teneral status of the sand flies captured in the emergence traps was confirmed by laboratory studies that determined the rate of terminalia rotation in male L. longipalpis and the rate of cuticular growth layer formation of the thoracic phragma in both sexes of this species. A total of 58 teneral sand flies was captured during the study period (49 wk). Fifteen specimens were L. longipalpis; of these 11 (5 sand flies per square meter) were captured near pigpens, 3 (1.4 sand flies per square meter) were captured near rock resting sites, and 1 (1.6 sand flies per square meter) was collected at the base of a tree. The remainder of the sand flies were either L. trinidadensis (Newstead) or L. cayennensis (Flock & Abonnenc). Our results indicate that L. longipalpis larvae were dispersed widely in sites near houses, rather than concentrated in a few optimal microhabitats. PMID:9439128

  16. DNA vaccine against visceral leishmaniasis: a promising approach for prevention and control.

    Kumar, A; Samant, M

    2016-05-01

    The visceral leishmaniasis (VL) caused by Leishmania donovani parasite severely affects large populations in tropical and subtropical regions of the world. The arsenal of drugs available is limited, and resistance is common in clinical field isolates. Therefore, vaccines could be an important alternative for prevention against VL. Recently, some investigators advocated the protective efficacy of DNA vaccines, which induces the T cell-based immunity against VL. The vaccine antigens are selected as conserved in various Leishmania species and provide a viable strategy for DNA vaccine development. Our understanding for DNA vaccine development against VL is not enough and much technological advancement is required. Improved formulations and methods of delivery are required, which increase the uptake of DNA vaccine by cells; optimization of vaccine vectors/encoded antigens to augment and direct the host immune response in VL. Despite the many genes identified as vaccine candidates, the disappointing potency of the DNA vaccines in VL underscores the challenges encountered in the efforts to translate efficacy in preclinical models into clinical realities. This review will provide a brief background of DNA vaccines including the insights gained about the design, strategy, safety issues, varied candidates, progress and challenges that play a role in their ability against VL. PMID:27009772

  17. Abundance of Lutzomyia longipalpis in urban households as risk factor of transmission of visceral leishmaniasis

    Vianna, Elisa Neves; Morais, Maria Helena Franco; de Almeida, Andréa Sobral; Sabroza, Paulo Chagastelles; Reis, Ilka Afonso; Dias, Edelberto Santos; Carneiro, Mariângela

    2016-01-01

    Urban occurrence of human and canine visceral leishmaniasis (VL) is linked to households with characteristics conducive to the presence of sand flies. This study proposes an ad hoc classification of households according to the environmental characteristics of receptivity to phlebotominae and an entomological study to validate the proposal. Here we describe the phlebotominae population found in intra- and peridomiciliary environments and analyse the spatiotemporal distribution of the VL vector Lutzomyia longipalpis of households receptive to VL. In the region, 153 households were classified into levels of receptivity to VL followed by entomological surveys in 40 of those properties. Kruskal-Wallis verified the relationship between the households’ classification and sand fly abundance and Kernel analysis evaluated L. longipalpis spatial distribution: of the 740 sand flies were captured, 91% were L. longipalpis; 82% were found peridomiciliary whilst the remaining 18% were found intradomiciliary. No statistically significant association was found between sandflies and households levels. L. longipalpis counts were concentrated in areas of high vulnerability and some specific households were responsible for the persistence of the infestation. L. longipalpis prevails over other sand fly species for urban VL transmission. The entomological study may help target the surveillance and vector control strategies to domiciles initiating and/or maintaining VL outbreaks. PMID:27223866

  18. Epidemiology of human immunodeficiency virus-visceral leishmaniasis-co-infection.

    Naufal Spir, Patrícia Rodrigues; Zampieri D'Andrea, Lourdes Aparecida; Fonseca, Elivelton Silva; Prestes-Carneiro, Luiz Euribel

    2016-04-01

    In Brazil, the rates of mother-to-child-transmission (MTCT) of human immunodeficiency virus (HIV) decreased from 20% to 1-2% in some regions. However, the country contains 90% of individuals infected with visceral leishmaniasis (VL) in Latin America, and the west region of São Paulo state faces an alarming expansion of the disease. We describe the epidemiological aspects of the expanding infection of VL and a case report of an HIV-VL-co-infected child from the west region of São Paulo state. The patient was an AIDS-C3 with low levels of CD4, high viral load, severe diarrhea, oral and perineal candidiasis, severe thrombocytopenia, and protein-caloric malnourishment. She evolved with sepsis, renal and cardiac failure. An rK rapid diagnosis test, indirect fluorescent antibody test (IFAT), and bone marrow aspirate were performed for VL. Her symptoms improved significantly after liposomal amphotericin B administration. From the 45 municipalities that compose the Regional Health Department of Presidente Prudente, Lutzomyia longipalpis vectors were found in 58% of them. VL infected dogs were found in 33% of those municipalities, infected dogs and humans were found in 29%, 20% are starting and 33% of the municipalities are preparing VL investigation. It is likely, in this patient, that VL advanced the clinical progression of the HIV disease and the development of AIDS severity. Supported by favorable conditions, the region becomes a new frontier of VL in Brazil. PMID:23834783

  19. Comparison of clinical samples for visceral Leishmaniasis diagnosis in asymptomatic dogs by PCR hybridization

    Ferreira, Sidney A.; Ituassu, Leonardo T.; Melo, Maria N. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Parasitologia], e-mail: saninoalmeida@gmail.com, e-mail: Itituassu@yahoo.com.br, e-mail: melo@icb.ufmg.br; Leite, Rodrigo S.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-CNEN/MG), Belo Horizonte, MG (Brazil)], e-mail: rleite2005@gmail.com, e-mail: antero@cdtn.br

    2009-07-01

    The canine visceral leishmaniasis (CVL) diagnosis still represents a challenge because of complexity of this disease. The aim of present study was to compare different clinical samples for diagnosis of CVL by Polymerase Chain Reaction (PCR) combined with hybridization of {sup 32}P labeled probes. Bone marrow (BM), skin biopsy (SB), peripheral blood (PB) and conjunctival swab (CS) were used in this work. With this purpose 40 asymptomatic dogs, all positive by parasitological test, were obtained. From each animal were collected SB with sterile punches from ear internal surface, 1.0 mL of PB, BM aspirates from sternum and CS from both lower eyelid. Each clinical sample was submitted to suitable DNA purification process and PCR-hybridization assays. The positive results obtained with PCR were 55%, 25%, 30% and 22.5% for CS, BM, SB and PB respectively while the PCR followed by hybridization showed a positivity of 87.5%, 50%, 45% and 27.5% respectively. The hybridization assay was able to increase the PCR positivity in all kinds of clinical samples. The best performance was obtained using CS samples. We concluded that the PCR associated with DNA radioactive probes was a very sensitive tool for diagnosis of CVL in asymptomatic dogs and the CS has an important potential for regular screening of dogs. (author)

  20. Risk Factors for Death from Visceral Leishmaniasis in an Urban Area of Brazil.

    Angelita F Druzian

    Full Text Available Over the last three decades, the epidemiological profile of visceral leishmaniasis (VL has changed with epidemics occurring in large urban centers of Brazil, an increase in HIV/AIDS co-infection, and a significant increase in mortality. The objective of this study was to identify the risk factors associated with death among adult patients with VL from an urban endemic area of Brazil.A prospective cohort study included 134 adult patients with VL admitted to the University Hospital of the Federal University of Mato Grosso do Sul between August 2011 and August 2013.Patients ranged from 18 to 93 years old, with a mean age of 43.6 (±15.7%. Of these patients, 36.6% were co-infected with HIV/AIDS, and the mortality rate was 21.6%. In a multivariate analysis, the risk factors associated with death were secondary bacterial infection (42.86, 5.05-363.85, relapse (12.17, 2.06-71.99, edema (7.74, 1.33-45.05 and HIV/AIDS co-infection (7.33, 1.22-43.98.VL has a high mortality rate in adults from endemic urban areas, especially when coinciding with high rates of HIV/AIDS co-infection.

  1. Phlebotomine sand flies (Diptera: Psychodidae) transmitting visceral leishmaniasis and their geographical distribution in China: a review.

    Guan, Li-Ren; Zhou, Zheng-Bin; Jin, Chang-Fa; Fu, Qing; Chai, Jun-Jie

    2016-01-01

    After the existence of phlebotomine sand flies was first reported in China in 1910, the distribution of different species and their role in the transmission of visceral leishmaniasis (VL) have been extensively studied. Up until 2008, four species have been verified as vectors of VL, namely, Phlebotomus chinensis (Ph. sichuanensis), Ph. longiductus (Ph. chinensis longiductus), Ph. wui (Ph. major wui), and Ph. alexandri. The sand fly species vary greatly depending on the natural environments in the different geographic areas where they are endemic. Ph. chinensis is euryecious and adaptable to different ecologies, and is thus distributed widely in the plain, mountainous, and Loess Plateau regions north of the Yangtze River. Ph. longiductus is mainly distributed in ancient oasis areas south of Mt. Tianshan in the Xinjiang Uygur autonomous region. Ph. wui is the predominant species in deserts with Populus diversifolia and Tamarix vegetation in Xinjiang and the western part of the Inner Mongolia autonomous region. Finally, Ph. alexandri is steroecious and found only in stony desert areas, such as at the foot of the mountains in Xinjiang and the western Hexi Corridor, in Gansu province. This review summarized the relationship between the geographic distribution pattern of the four sand fly species and their geographical landscape in order to foster research on disease distribution and sand fly control planning. Furthermore, some problems that remained to be solved about vectors of VL in China were discussed. PMID:26906187

  2. Autoantibodies in a Three-Year-Old Girl with Visceral Leishmaniasis: A Potential Diagnostic Pitfall

    Gholamreza Pouladfar

    2016-01-01

    Full Text Available Visceral leishmaniasis (VL, a life-threatening parasitic infection, is endemic in the Mediterranean region. Diagnosis of VL is based on epidemiologic, clinical, and laboratory findings. However, sometimes, clinical features and laboratory findings overlap with those of autoimmune diseases. In some cases, autoantibodies are detected in patients with VL and this could be a potential diagnostic pitfall. In this study, we have reported on a three-year-old girl from a VL-endemic area in Iran, who presented with prolonged fever and splenomegaly. Bone marrow examination, serologic tests, and the molecular PCR assay were performed; however, results were inconclusive. The levels of anti-double stranded DNA, cytoplasmic antineutrophil cytoplasmic autoantibody, and perinuclear antineutrophil cytoplasmic autoantibody were elevated and, at the end, splenic biopsy was performed. The splenic tissue PCR test detected the DNA of Leishmania infantum. The patient’s condition improved with anti-Leishmania therapy, and the autoantibodies disappeared within the following four months. Clinical presentations and laboratory findings of VL and autoimmune diseases may overlap in some patients.

  3. IDENTIFICATION OF CANINE VISCERAL LEISHMANIASIS IN A PREVIOUSLY UNAFFECTED AREA BY CONVENTIONAL DIAGNOSTIC TECHNIQUES AND CELL-BLOCK FIXATION

    Tuanne Rotti ABRANTES

    2016-01-01

    Full Text Available After the report of a second case of canine visceral leishmaniasis (CVL in São Bento da Lagoa, Itaipuaçu, in the municipality of Maricá, Rio de Janeiro State, an epidemiological survey was carried out, through active search, totaling 145 dogs. Indirect immunofluorescence assay (IFA, enzyme-linked immunosorbent assay (ELISA, and rapid chromatographic immunoassay based on dual-path platform (DPP(r were used to perform the serological examinations. The parasitological diagnosis of cutaneous fragments was performed by parasitological culture, histopathology, and immunohistochemistry. In the serological assessment, 21 dogs were seropositive by IFA, 17 by ELISA, and 11 by DPP(r, with sensitivity of 66.7%, 66.7% and 50%, and specificity of 87.2%, 90.2% and 94%, respectively for each technique. The immunohistochemistry of bone marrow using the cell-block technique presented the best results, with six positive dogs found, three of which tested negative by the other parasitological techniques. Leishmania sp. was isolated by parasitological culture in three dogs. The detection of autochthonous Leishmania infantum in Itaipuaçu, and the high prevalence of seropositive dogs confirm the circulation of this parasite in the study area and alert for the risk of expansion in the State of Rio de Janeiro.

  4. Direct Agglutination Test and Enzyme Linked Immunosorbent Assay with Urine Samples for the Diagnosis of Visceral Leishma-niasis

    Sarkari B

    2007-07-01

    Full Text Available Background: Visceral leishmaniasis (VL or Kala azar is an infectious disease caused by various species of Leishmania parasites. The aim of this study was to detect and compare the presence of anti-Leishmania antibodies in the urine of vis-ceral leishmaniasis patients using ELISA and DAT methods."nMethods: A total of 30 urine samples were collected from VL patients referred to Shiraz (southeast of Iran hospitals. Moreover 31 urine samples were collected from healthy individuals and patients with other diseases such as malaria, brucellosis, hydatidosis and cutaneous leishmaniasis. Collected samples were examined to detect anti-Leishmania antibod-ies in urine, using ELISA and DAT."nResults: Anti-Leishmania antibody was detected in urine of 18 out of 30 (60% VL patients by DAT while ELISA detected anti-Leishmania antibodies in urine of 28 out of 30 (93.3% of VL cases. Sensitivity and specificity of urine-based DAT was 60% and 83.9%, respectively while sensitivity and specificity of urine-based ELISA were 93.3% and 93.5%, corre-spondingly. "nConclusion: Urine-based DAT and ELISA have a reasonable specificity and sensitivity in diagnosis of VL. Accordingly, urine-based ELISA might be a suitable alternative for serum based assays for diagnosis of VL.

  5. Mimotope-based vaccines of Leishmania infantum antigens and their protective efficacy against visceral leishmaniasis.

    Lourena Emanuele Costa

    Full Text Available BACKGROUND: The development of cost-effective prophylactic strategies to prevent leishmaniasis has become a high-priority. The present study has used the phage display technology to identify new immunogens, which were evaluated as vaccines in the murine model of visceral leishmaniasis (VL. Epitope-based immunogens, represented by phage-fused peptides that mimic Leishmania infantum antigens, were selected according to their affinity to antibodies from asymptomatic and symptomatic VL dogs' sera. METHODOLOGY/MAIN FINDINGS: Twenty phage clones were selected after three selection cycles, and were evaluated by means of in vitro assays of the immune stimulation of spleen cells derived from naive and chronically infected with L. infantum BALB/c mice. Clones that were able to induce specific Th1 immune response, represented by high levels of IFN-γ and low levels of IL-4 were selected, and based on their selectivity and specificity, two clones, namely B10 and C01, were further employed in the vaccination protocols. BALB/c mice vaccinated with clones plus saponin showed both a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with individual clones or L. infantum extracts. Additionally, these animals, when compared to control groups (saline, saponin, wild-type phage plus saponin, or non-relevant phage clone plus saponin, showed significant reductions in the parasite burden in the liver, spleen, bone marrow, and paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, mainly by CD8+ T cells, against parasite proteins. These animals also presented decreased parasite-mediated IL-4 and IL-10 responses, and increased levels of parasite-specific IgG2a antibodies. CONCLUSIONS/SIGNIFICANCE: This study describes two phage clones that mimic L. infantum antigens, which were directly used as immunogens in vaccines and presented Th1-type immune responses, and that significantly reduced the

  6. Imported visceral leishmaniasis: diagnostic dilemmas and comparative analysis of three assays.

    Iqbal, Jamshaid; Hira, Parsotam R; Saroj, Grover; Philip, Reeni; Al-Ali, Faiza; Madda, Patrick J; Sher, Ali

    2002-02-01

    The present study evaluates the performances of three noninvasive serological assays for the detection of immunoglobulin G antibodies to leishmania antigen for the diagnosis of imported cases of kala azar (visceral leishmaniasis [VL]) in a country, Kuwait, where the disease is not endemic. A total of 323 individuals including 21 patients with documented cases of VL, 72 individuals with suspected cases of VL, 155 patients with other parasitic infections, and 75 healthy control individuals were tested by indirect hemagglutination assay (IHA; Behring Diagnostics GmbH, Marburg, Germany), indirect fluorescent-antibody assay (IFA; bioMerieux sa, Marcy l'Etoile, France), and a qualitative membrane-based immunoassay with recombinant leishmania antigen K39 (strip-test; Intersep Ltd, Berkshire, United Kingdom). Our data show that IHA is the most sensitive test (100%), followed by IFA (86.6%) and the strip-test (80.0%). The strip-test was the most specific (100%) of the three assays, followed by IFA (93.0%) and IHA (86.0%). However, the strip-test failed to detect at least three confirmed cases of VL. We conclude that IHA is preferred over IFA and the strip-test for the screening of individuals with suspected cases of VL, especially in a country where VL is not endemic and where the number of cases is regular but limited. The details about some of the patients with VL are presented to highlight the diversity of clinical presentations and problems encountered in the diagnosis of VL in a country where VL is not endemic. PMID:11825959

  7. Human Visceral Leishmaniasis in Kermanshah Province, Western Iran, During 2011-2012

    H Bashiri

    2012-12-01

    Full Text Available Background: Visceral leishmaniasis (VL or kala-azar is a parasitic disease caused by the species of Leishmania donovani complex. It is endemic in some parts of provinces of Iran. According to the reported cases of VL in Kermanshah Province in recent years, this study was conducted to determine the seroprevalence of VL in high risk villages of the province.Metods: Totally, 1622 serum samples obtained from children under 15 years old and 178 from adults in 22 villages of studied areas. Serum samples were examined by direct agglutination test (DAT for the detection of anti-Leishmania antibodies. Data were analyzed using SPSS software ver.11.5.Results: Only 6 serum samples (0.33% showed anti-Leishmania antibodies against L.infantum at titers ≥ 1/3200. Four of the seropositive cases had a history of kala-azar and Leishman bodies were seen in their bone marrows. The highest (0.5% and lowest (0.29% seroprevalence was seen in the age groups of 5-9 and 10-14 years old, respectively. None of the adults were seropositive. There were not any significant differences be­tween the rate of seropositivity in males (0.36% and females (0.31%. 66.7% of seropositive individuals showed clinical manifestations. The most important symptoms in Kala-azar patients were fever, hepato-spleenome­gally and anemia.Conclusion: Kala-azar is occurred sporadically in Kermanshah Province. But presence of significant number of positive sera confirms the necessity for attention of people and clinicians to kala-azar.

  8. The Leishmania infantum PUF proteins are targets of the humoral response during visceral leishmaniasis

    Requena Jose M

    2010-01-01

    Full Text Available Abstract Background RNA-binding proteins of the PUF family share a conserved domain consisting of tandemly repeated 36-40 amino acid motifs (typically eight known as Puf repeats. Proteins containing tandem repeats are often dominant targets of humoral responses during infectious diseases. Thus, we considered of interest to analyze whether Leishmania PUF proteins result antigenic during visceral leishmaniasis (VL. Findings Here, employing whole-genome databases, we report the composition, and structural features, of the PUF family in Leishmania infantum. Additionally, the 10 genes of the L. infantum PUF family were cloned and used to express the Leishmania PUFs in bacteria as recombinant proteins. Finally, the antigenicity of these PUF proteins was evaluated by determining levels of specific antibodies in sera from experimentally infected hamsters. The Leishmania PUFs were all recognized by the sera, even though with different degree of reactivity and/or frequency of recognition. The reactivity of hamster sera against recombinant LiPUF1 and LiPUF2 was particularly prominent, and these proteins were subsequently assayed against sera from human patients. High antibody responses against rLiPUF1 and rLiPUF2 were found in sera from VL patients, but these proteins resulted also recognized by sera from Chagas' disease patients. Conclusion Our results suggest that Leishmania PUFs are targets of the humoral response during L. infantum infection and may represent candidates for serodiagnosis and/or vaccine reagents; however, it should be kept in mind the cross-reactivity of LiPUFs with antibodies induced against other trypanosomatids such as Trypanosoma cruzi.

  9. Current epidemiological profile and features of visceral leishmaniasis in people's republic of China

    Wang Jun-Yun

    2012-02-01

    Full Text Available Abstract Background Visceral leishmaniasis (VL is still an important public health problem in China. In recent years endemic regions spread, prevalence increased, and even an outbreak of the disease occurred in China due to global warming and population movement. It is essential to elucidate the current epidemic situation and epidemiological characteristics of VL for designing control policy. In the present study we describe the current epidemiological profile and characteristics of VL in China based on retrospectively reviewing of VL cases reported between 2005 and 2010 by a passive surveillance system. Methods The present study was a retrospective review of VL cases notified between 2005 and 2010 based on the passive surveillance data. The data were tabulated, diagrammatized and analyzed through descriptive statistics in a Microsoft Excel spreadsheet. Results A total of 2450 VL cases were notified, with a mean of 408 cases per year. 61 counties were identified as endemic area with 2224 autochthonous cases, and the other 118 counties as non-endemic areas with 226 imported cases. 97.71% of cases were concentrated in Xinjiang, Gansu and Sichuan Provinces. 9 major counties reported a mean of > 10 cases per year, with a total of 1759 cases reported. Different types of VL revealed distinct epidemiological characteristics. Conclusions The number of VL cases and endemic counties both increased in the period 2005-2010 in China. Different type or sub-type of VL revealed distinct epidemiological characteristics. Therefore, differential control measures must be taken in different endemic areas against incidence increase and endemic area spread.

  10. A proposition on the genetic history of visceral Leishmaniasis:glimpses from the side of parasite

    The recorded history of diseases affecting man, contains hardly any reliable information on their state beyond few centuries ago. This is particularly true for diseases having symptoms common to others as is typically the case of visceral Leishmaniasis. Our increased understanding of the biology and epidemiology of VL during the last hundred years or so, nevertheless, raise more questions than answers. For example: what is the possible role played by such disease in shaping the population structure and range of expaion of their human host. Could resistance of certain populations to disease be explained by the distribution of less virulent parasite strains e.g. (Leishmania infantum) or by ancient episodes of strong selection? data obtained from molecular analysis of parasites isolated from patients in Sudan, indicates that the current outbreak is probably a recent event caused by stocks of closely related parasites. More recently, mitochondrial hapoltypes analysis gave further support to the homogeneity of these parasite populations. Cladistic analysis of Leishmania donovani strains from different continents make a clear distinction between two clades; one containing parasites of the infantum group in different continents and the other includes members of the donovani group in Africa and Asia. Furthermore, we did not encounter-a-presence-of Leishmania infantum specific sequence within paraite population sampled in the areas, covered by the outbreaks. The parasites from Sudan presented with the most ancestral haplotypes. The disease in Sudan may have passed through short periods of protraction and expansion, which may have resulted in stability of the parasite genetic population structure, but rather a fragile host-parasite relationship. Studying host sequence may reveal equally interesting situations and shed more light on these-aspects.(Author)

  11. Experimental infection of dogs with Leishmania and saliva as a model to study Canine Visceral Leishmaniasis.

    Dirceu Joaquim Costa

    Full Text Available BACKGROUND: Canine Visceral Leishmaniasis (CVL is a zoonotic disease caused by Leishmania infantum, transmitted by the bite of Lutzomyia longipalpis sand flies. Dogs are the main domestic reservoir of the parasite. The establishment of an experimental model that partially reproduces natural infection in dogs is very important to test vaccine candidates, mainly regarding those that use salivary proteins from the vector and new therapeutical approaches. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we describe an experimental infection in dogs, using intradermal injection of Leishmania infantum plus salivary gland homogenate (SGH of Lutzomyia longipalpis. Thirty-five dogs were infected with 1×10(7 parasites combined with five pairs of Lutzomyia longipalpis salivary glands and followed for 450 days after infection and clinical, immunological and parasitological parameters were evaluated. Two hundred and ten days after infection we observed that 31,4% of dogs did not display detectable levels of anti-Leishmania antibodies but all presented different numbers of parasites in the lymph nodes. Animals with a positive xenodiagnosis had at least 3,35×10(5 parasites in their lymph nodes. An increase of IFN-γ and IL-10 levels was detected during infection. Twenty two percent of dogs developed symptoms of CVL during infection. CONCLUSION: The infection model described here shows some degree of similarity when compared with naturally infected dogs opening new perspectives for the study of CVL using an experimental model that employs the combination of parasites and sand fly saliva both present during natural transmission.

  12. Clinical and histopathological features of myocarditis in dogs with visceral leishmaniasis

    F.P. dos Santos

    2015-12-01

    Full Text Available Visceral leishmaniasis (VL is a cosmopolitan parasitic zoonosis that can promote myocarditis and heart rate changes in canine and human hosts. Thus, histopathological aspects of the myocardium and clinical, hematological, biochemical, radiological and electrocardiographic data were evaluated in a group of 36 dogs naturally infected with VL (VLG and compared to data from 15 non-infected dogs (CG=Control Group. A prevalence of asymptomatic dogs was present in the CG (100% and polysymptomatic dogs in the VLG (66%. In addition, two dogs in the VLG demonstrated systolic murmurs in the mitral valve region: one with a II/VI intensity and the other with a III/VI intensity. The mean values of RBC, hemoglobin and hematocrit were lower in dogs in VLG and were associated with higher values of total protein, total leukocytes, neutrophils, creatine kinase overall (CK and the CK-MB fraction (CK-MB. The absence of radiographic changes was accompanied by a predominance of respiratory sinus arrhythmia associated with episodes of migratory pacemaker and sinus arrest in dogs in VLG (75%, sinus rhythm in dogs in CG (60% and decreased P wave amplitude in VLG electrocardiography. Mononuclear cell infiltration was detected in the myocardium of 77,8% of dogs in GVL and classified primarily as mild multifocal lymphohistioplasmacytic. Amastigotes were detected in only one dog, which did not allow the association between myocarditis and parasitism, although the myocardial lesions that were found constitute irrefutable evidence of myocarditis in the VLG dogs, accompanied by lenient electrocardiographic changes compared to CG.

  13. Risk factors for visceral Leishmaniasis among residents and migrants in Kafta-Humera, Ethiopia.

    Daniel Argaw

    2013-11-01

    Full Text Available BACKGROUND: Visceral leishmaniasis is a lethal parasitic disease transmitted by phlebotomine sand flies. The largest focus of VL in Ethiopia is located in the lowland region bordering Sudan, where the epidemiology is complicated by the presence of thousands of seasonal agricultural workers who live under precarious conditions. METHODOLOGY/PRINCIPAL FINDINGS: We conducted two parallel case-control studies to identify factors associated with VL risk in residents and migrants. The studies were conducted from 2009 to 2011 and included 151 resident cases and 157 migrant cases, with 2 matched controls per case. In multivariable conditional regression models, sleeping under an acacia tree at night (odds ratios (OR 5.2 [95% confidence interval 1.7-16.4] for residents and 4.7 [1.9-12.0] for migrants, indicators of poverty and lower educational status were associated with increased risk in both populations. Strong protective effects were observed for bed net use (OR 0.24 [0.12-0.48] for net use in the rainy season among residents, OR 0.20 [0.10-0.42] for any net use among migrants. For residents, living in a house with thatch walls conferred 5-fold and sleeping on the ground 3-fold increased risk. Among migrants, the risk associated with HIV status was borderline significant and sleeping near dogs was associated with 7-fold increased risk. CONCLUSIONS/SIGNIFICANCE: Preventive strategies should focus on ways to ensure net usage, especially among migrant workers without fixed shelters. More research is needed to understand migration patterns of seasonal labourers and vector bionomics.

  14. A Correlative Study of Splenic Parasite Score and Peripheral Blood Parasite Load Estimation by Quantitative PCR in Visceral Leishmaniasis.

    Sudarshan, Medhavi; Singh, Toolika; Chakravarty, Jaya; Sundar, Shyam

    2015-12-01

    Parasitological diagnosis of visceral leishmaniasis (VL) by splenic smear is highly sensitive, but it is associated with the risk of severe hemorrhage. In this study, the diagnosis of VL using quantitative PCR (qPCR) in peripheral blood was evaluated in 100 patients with VL. Blood parasitemia ranged from 5 to 93,688 leishmania parasite genomes/ml of blood and positively correlated with splenic score (P<0.0001; r2=0.58). Therefore, quantification of parasite genomes by qPCR can replace invasive procedures for diagnostic and prognostic evaluations. PMID:26400788

  15. Leishmaniasis visceral en la Argentina: Notificación y situación vectorial (2006-2012)

    Ignacio T. Gould; Mónica S. Perner; María S. Santini; Silvina B. Saavedra; Gisella Bezzi; Mariana I. Maglianese; Julián G. Antman; Jorge A. Gutiérrez; Oscar D. Salomón

    2013-01-01

    La leishmaniasis visceral (LV) en la Argentina se notifica obligatoriamente a través del Sistema Nacional de Vigilancia de la Salud (SNVS). El análisis de la notificación muestra un total de 103 casos distribuidos en cuatro provincias, siendo Misiones la de mayor casuística con un total de 80 casos en 15 localidades, desde mayo 2006 hasta julio de 2012. Los niños de 0 a 15 años de edad son el grupo con mayor incidencia. En el año 2004 fue registrado por primera vez el riesgo de LV urbana endé...

  16. Identification and Characterization of a Novel, 37-Kilodalton Leishmania donovani Antigen for Diagnosis of Indian Visceral Leishmaniasis

    Kumar, Subodh; Kumar, Dinesh; Chakravarty, Jaya; Sundar, Shyam

    2011-01-01

    The biggest challenge in the serological diagnosis of visceral leishmaniasis (VL) is to find a biomarker with a high specificity. This study was undertaken to identify novel Leishmania donovani antigens to solve the existing problem. The soluble L. donovani promastigote antigen was separated by SDS-PAGE, and a Western blot was probed with pooled sera of five subjects with confirmed VL before (n = 9 pools) and after (n = 9 pools) treatment and at the 6-month follow-up visit (n = 9 pools), heal...

  17. Severe clinical presentation of visceral leishmaniasis in naturally infected dogs with disruption of the splenic white pulp.

    Isadora S Lima

    Full Text Available In this work, we investigated the association between the disruption of splenic lymphoid tissue and the severity of visceral leishmaniasis in dogs. Clinical and laboratory data from 206 dogs were reviewed. Spleen sections collected during the euthanasia of these animals were analyzed, and the splenic lymphoid tissue samples were classified as well organized (spleen type 1, slightly disorganized (spleen type 2, or moderately to extensively disorganized (spleen type 3. Of 199 dogs with evidence of Leishmania infection, 54 (27% had spleen type 1, 99 (50% had spleen type 2, and 46 (23% had spleen type 3. The number of clinical signs associated with visceral leishmaniasis was significantly higher in the animals with evidence of Leishmania infection and spleen type 2 or 3 than in the animals with spleen type 1. Alopecia, anemia, dehydration, dermatitis, lymphadenopathy, and onychogryphosis were all more frequent among animals with evidence of Leishmania infection and spleen type 3 than among the dogs with evidence of Leishmania infection and spleen type 1. The association between the severity of canine visceral leishmaniasis and the disorganization of the splenic lymphoid tissue was even more evident in the group of animals with positive spleen culture. Conjunctivitis and ulceration were also more common in the animals with spleen type 3 than in the animals with spleen type 1. The serum levels (median, interquartile range of albumin (1.8, 1.4-2.3 g/dL and creatinine (0.7, 0.4-0.8 mg/dL were significantly lower and the serum levels of aspartate aminotransferase were significantly higher (57, 39-95 U in animals with spleen type 3 than in animals with spleen type 1 (2.8, 2.4-3.4 g/dL; 0.9, 0.7-1.2 mg/dL and 23, 20-32 U, respectively. Our data confirm the hypothesis that disruption of the splenic lymphoid tissue is associated with a more severe clinical presentation of canine visceral leishmaniasis.

  18. Sand fly salivary proteins induce strong cellular immunity in a natural reservoir of visceral leishmaniasis with adverse consequences for Leishmania.

    Nicolas Collin; Regis Gomes; Clarissa Teixeira; Lily Cheng; Andre Laughinghouse; Ward, Jerrold M.; Dia-Eldin Elnaiem; Laurent Fischer; Valenzuela, Jesus G.; Shaden Kamhawi

    2009-01-01

    Immunity to a sand fly salivary protein protects against visceral leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-gamma at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35...

  19. Visceral Leishmaniasis Prevalence and Associated Risk Factors in the Saran District of Bihar, India, from 2009 to July of 2011

    Perry, Diana; Dixon, Kandice; Garlapati, Rajesh; Gendernalik, Alex; Poché, David; Poché, Richard

    2013-01-01

    India is one of three countries that account for an estimated 300,000 of 500,000 cases of visceral leishmaniasis (VL) occurring annually. Bihar State is the most affected area of India, with more than 90% of the cases. Surveys were conducted in two villages within the Saran district of Bihar, India, from 2009 to July of 2011 to assess risk factors associated with VL. Forty-five cases were identified, and individuals were given an oral survey. The results indicated that men contracted the dise...

  20. Application of predictive degree day model for field development of sandfly vectors of visceral leishmaniasis in northwest of Iran

    M.A. Oshaghi

    2009-12-01

    Full Text Available Background & objectives: Temperature plays a significant role in insect’s development where arise in temperature, accelerates the insect’s metabolic rates, increases egg production and makesblood feeding more frequent. It also shortens the time period required for the development ofpathogens within insects. Visceral leishmaniasis (VL is one of the most important vector-bornediseases transmitted by different sandfly species. In this study, a phenological model was used toestimate the number of generations, peak activity and temporal variability of sandflies in the mainVL foci in northwest Iran.Methods: Development requirements of different life stages of a Phlebotomus papatasi laboratorycolony were measured and were subjected to the formula for calculation of accumulated degree day(ADD for field sandflies using the online soft (UC IPM, using horizontal cut-off method andsingle triangle model. Sandflies population dynamics was monitored in the field during the seasonalactivity in the region and its association with the ADD was tested using SAS software.Results: Populations of sandflies accommodated well with the amount of accumulated degree days(ADD in the region. During the seasonal activity, a total of 639 ADD were produced which wasenough to support one complete life cycle and growth of the next generation up to late larvalinstar. Larvae of the second generation hibernate through winter and the first adult populationappears in the mid to late June of the next year when they receive at least 182 ADD from thebeginning of the spring. The highest population density of sandflies was observed in early August,followed by a rapid decrease in early September, with the adult population disappearing completelyin late September. This is the first degree day model related to sandflies in the most important VLfoci of Iran.Interpretation & conclusion: Further studies in various regions with variable climate arerecommended in order to better estimate and

  1. A comparison of four DNA extraction protocols for the analysis of urine from patients with visceral leishmaniasis

    Maria Almerice Lopes da Silva

    2014-04-01

    Full Text Available Introduction Polymerase chain reaction (PCR may offer an alternative diagnostic option when clinical signs and symptoms suggest visceral leishmaniasis (VL but microscopic scanning and serological tests provide negative results. PCR using urine is sensitive enough to diagnose human visceral leishmaniasis (VL. However, DNA quality is a crucial factor for successful amplification. Methods A comparative performance evaluation of DNA extraction methods from the urine of patients with VL using two commercially available extraction kits and two phenol-chloroform protocols was conducted to determine which method produces the highest quality DNA suitable for PCR amplification, as well as the most sensitive, fast and inexpensive method. All commercially available kits were able to shorten the duration of DNA extraction. Results With regard to detection limits, both phenol: chloroform extraction and the QIAamp DNA Mini Kit provided good results (0.1 pg of DNA for the extraction of DNA from a parasite smaller than Leishmania (Leishmania infantum (< 100fg of DNA. However, among 11 urine samples from subjects with VL, better performance was achieved with the phenol:chloroform method (8/11 relative to the QIAamp DNA Mini Kit (4/11, with a greater number of positive samples detected at a lower cost using PCR. Conclusion Our results demonstrate that phenol:chloroform with an ethanol precipitation prior to extraction is the most efficient method in terms of yield and cost, using urine as a non-invasive source of DNA and providing an alternative diagnostic method at a low cost.

  2. Molecular and Seroepidemiological Survey of Visceral Leishmaniasis Among Humans and Domestic Dogs in Mazandaran Province, North of Iran

    M Sharif

    2011-09-01

    Full Text Available Background: New cases of visceral leishmaniasis (VL have been reported recently in some parts of Mazandaran Province, north of Iran where the first human case of VL was reported in 1949. This study aimed to determine the present status of Leishmania infantum infection among humans and domestic dogs using serological and molecular methods in central parts of Mazandaran Province.Methods: In this cross-sectional study, blood samples were randomly collected from 402 humans and forty-nine domestic dogs throughout 2009 and 2010 in the central part of Mazandaran Province including Semeskadeh and Kiakola districts where recent cases of human visceral leishmaniasis had been reported there. All the collected samples were tested by direct agglutination test (DAT for the detection of anti-Leishmania infantum antibodies as well as convenience PCR assay on whole blood samples for detection of leishmanial infection and identification of Leishmania species.Results: None of 402 collected human (402 and dog (49 blood samples showed anti Leishmania infantum antibodies at titers 1:3200 and 1:320 as cut-off values of DAT, respectively but only 2 of domestic dogs (4.1 % were found PCR-positive corresponding to L .infantum.Conclusion: This study confirms the circulation of L. infantum at least among domestic dogs and highlights the sporadic pattern of VL in the studied areas. Further investigations regarding to sand flies fauna and wild canines as reservoir hosts of the disease, are recommended.

  3. Could kDNA-PCR in Peripheral Blood Replace the Examination of Bone Marrow for the Diagnosis of Visceral Leishmaniasis?

    de Godoy, Natalia Souza; Andrino, Marcos Luiz Alves; de Souza, Regina Maia; Gakiya, Erika; Amato, Valdir Sabbaga; Lindoso, José Ângelo Lauletta

    2016-01-01

    The aim of this study was to evaluate whether the molecular (kDNA-PCR) and parasitological diagnosis in peripheral blood (PB) could replace the invasive and painful bone marrow collection (BM) in the diagnosis of visceral leishmaniasis (VL). PB from suspected VL patients was evaluated by parasitological and molecular techniques using as the gold standard (GS) a combination of clinical, epidemiological, and immunochromatographic test (PB-rK39) results and parasitological examination of BM. Based on the GS, 38 samples from 32 patients were grouped: Group 1, 20 samples of VL cases, and Group 2, 18 samples of non-VL cases. In order to evaluate the parasitological and molecular techniques in PB, the samples were examined. From Group 1, PB kDNA-PCR was positive in 20 samples and in 19 of 20 in BM kDNA-PCR examination. However, the parasitological examination of buffy coat was insensitive, being able to detect only 4 cases from Group 1. All samples from Group 2 were negative. We concluded that, for the diagnosis of visceral leishmaniasis, the parasitological examination of peripheral blood was not useful; however, molecular diagnosis by kDNA-PCR, performed in peripheral blood, could be useful to replace the parasitological examination of bone marrow. PMID:27597892

  4. Emergence of co-infection of visceral leishmaniasis in HIV-positive patients in northeast Iran: a preliminary study.

    Shafiei, Reza; Mohebali, Mehdi; Akhoundi, Behnaz; Galian, Meysam Sharifdini; Kalantar, Fathollah; Ashkan, Saeedeh; Fata, Abdolmajid; Farash, Bibi Razieh Hosseini; Ghasemian, Mehrdad

    2014-01-01

    Visceral leishmaniasis (VL) serosurvey was carried out on 49 HIV/AIDS patients among 500 asymptomatic HIV/infected patients who registered in the Khorasan Razavi Province during the last 14 years. HIV infections were detected by ELISA and confirmed using western blot assay at the AIDS centre of the Khorasan Razavi Province. All collected sera were screened using the direct agglutination test (DAT). The sera with anti-Leishmania infantum antibodies at a titre of 1:100 were considered positive for VL infection and serum titration was performed from 1:100 to 1:102,400. Nine (18.4%) patients were sero-positive according to DAT. The distribution of sera titrations were as follows: 1:100 (n = 6) 1:1600 (n = 1); 1:25,600 (n = 1) and 1:102,400 (n = 1). All sero-positive cases showed clinical signs and symptoms. The most predominant signs and symptoms of co-infection of visceral leishmaniasis in HIV-positive patients were pneumonia (n = 2), hepatosplenomegaly (n = 2), lymphadenopathy (n = 2), anaemia (n = 1), prolonged fever (n = 1) and cachexia (n = 1). Our finding shows that VL (or kala-azar) is an opportunistic disease in HIV-positive patients that may be occurred in VL endemic areas of Iran. PMID:24100200

  5. Health-seeking behaviour, diagnostics and transmission dynamics in the control of visceral leishmaniasis in the Indian subcontinent.

    Medley, Graham F; Hollingsworth, T Déirdre; Olliaro, Piero L; Adams, Emily R

    2015-12-01

    Countries in the Indian subcontinent have committed to reducing the incidence of kala-azar, a clinical manifestation of visceral leishmaniasis, to below 1 in 10,000 by 2020. We address the role of timing of use and accuracy of diagnostics in kala-azar control and elimination. We use empirical data on health-seeking behaviour and health-system performance from the Indian state of Bihar, Bangladesh and Nepal to parameterize a mathematical model. Diagnosis of cases is key to case management, control and surveillance. Treatment of cases prevents onward transmission, and we show that the differences in time to diagnosis in these three settings explain the observed differences in incidence. Shortening the time from health-care seeking to diagnosis is likely to lead to dramatic reductions in incidence in Bihar, bringing the incidence down to the levels seen in Bangladesh and Nepal. The results emphasize the importance of maintaining population and health-system awareness, particularly as transmission and disease incidence decline. We explore the possibility of diagnosing patients before the onset of clinical kala-azar (before 14 days fever), and show that this could have a marked impact on incidence, even for a moderately sensitive test. However, limited specificity (that results in false positives) is a major barrier to such a strategy. Diagnostic tests of high specificity used at an early stage of active infection, even if sensitivity is only moderate, could have a key role in the control of kala-azar, and prevent its resurgence when paired with the passive health-care system and tests of high sensitivity, such as the test for rK39 antibody response. PMID:26633763

  6. Development of an Immunochromatographic Test for Diagnosis of Visceral Leishmaniasis Based on Detection of a Circulating Antigen.

    Chun-hua Gao

    Full Text Available Visceral leishmaniasis (VL is a life-threatening disease caused by protozoan parasites of the Leishmania donovani complex. Early case detection followed by adequate treatment is essential to the control of VL. However, the available diagnostic tests are either invasive and require considerable expertise (parasitological demonstration of the parasite in tissue smears or unable to distinguish between past and active infection (serological methods. Therefore, we aimed to develop a lateral flow assay in the form of an immunochromatographic test (ICT device based on the detection of a circulating Leishmania antigen using monoclonal antibodies (mAbs.mAbs were produced by fusion of murine myeloma cells with splenocytes isolated from a mouse immunized with L. donovani soluble crude antigen. Out of 12 cloned hybridoma cell lines, two secreted mAbs recognizing the same leishmanial protein. These mAbs were used to produce an ICT as a sandwich assay for the detection of circulating antigen in serum and blood samples. The ICT was evaluated with 213 serum samples from VL patients living in VL endemic areas in China, and with 156 serum samples from patients with other diseases as well as 78 serum samples from healthy donors. Sensitivity, specificity and diagnostic efficiency of the new ICT was 95.8%, 98.7% and 97.3%, respectively. Compared with a commercially available antibody detecting ICT, our antigen-based ICT performed slightly better.The newly developed ICT is an easy to use and more accurate diagnostic tool which fulfils the performance and operational characteristics required for VL case detection under field and laboratory conditions. As our ICT detects a circulating antigen, it will also be useful in monitoring treatment success and diagnosing VL in immunocompromised patients.

  7. Sialoglycosylation of RBC in visceral leishmaniasis leads to enhanced oxidative stress, calpain-induced fragmentation of spectrin and hemolysis.

    Sajal Samanta

    Full Text Available Visceral leishmaniasis (VL caused by the intracellular parasite Leishmania donovani accounts for an estimated 12 million cases of human infection. It is almost always associated with anemia, which severely complicates the disease course. However, the pathological processes leading to anemia in VL have thus far not been adequately characterized to date. In studying the glycosylation patterns of peripheral blood cells we found that the red blood cells (RBC of VL patients (RBC(VL express eight 9-O-acetylated sialoglycoproteins (9-O-AcSGPs that are not detected in the RBC of healthy individuals (RBC(N. At the same time, the patients had high titers of anti-9-O-AcSGP IgG antibodies in their sera. These two conditions appear to be linked and related to the anemic state of the patients, as exposure of RBC(VL but not RBC(N to anti-9-O-AcSGPs antibodies purified from patient sera triggered a series of responses. These included calcium influx via the P/Q-type but not L-type channels, activation of calpain I, proteolysis of spectrin, enhanced oxidative stress, lipid peroxidation, externalization of phosphatidyl serine with enhanced erythrophagocytosis, enhanced membrane fragility and, finally, hemolysis. Taken together, this study suggests that the enhanced hemolysis is linked to an impairment of membrane integrity in RBC(VL which is mediated by ligand-specific interaction of surface 9-O-AcSGPs. This affords a potential explanation for the structural and functional features of RBC(VL which are involved in the hemolysis related to the anemia which develops in VL patients.

  8. Exploitation of lectinized lipo-polymerosome encapsulated Amphotericin B to target macrophages for effective chemotherapy of visceral leishmaniasis.

    Gupta, Pramod K; Asthana, Shalini; Jaiswal, Anil K; Kumar, Vivek; Verma, Ashwni K; Shukla, Prashant; Dwivedi, Pankaj; Dube, Anuradha; Mishra, Prabhat R

    2014-06-18

    We have designed lectin functionalized Lipo-polymerosome bearing Amphotericin B (Lec-AmB-L-Psome) for specific internalization via lectin receptors overexpressed on infected macrophages of mononuclear phagocytic system (MPS) for the effective management of intramacrophage diseases such as visceral leishmaniasis. The lipo-polymerosome composed of glycol chitosan-stearic acid copolymer (GC-SA25%) and model lipid cholesterol was surface-functionalized with lectin by the EDC/NHS carbodiimide coupling method. Our designed Lec-AmB-L-Psome showed >2-fold enhanced uptake and significantly higher internalization in macrophages as compared to AmB-L-Psome. Importantly, pharmacokinetic and organ distribution studies illustrate significantly higher accumulation of Lec-AmB-L-Psome in MPS especially in liver, spleen, and lung as compared to AmB-L-Psome, Ambisome, and Fungizone. The IC50 value demonstrated that Lec-AmB-L-Psome has 1.63, 2.23, and 3.43 times higher activity than AmB-L-Psome (p < 0.01), Ambisome (p < 0.05), and Fungizone (p < 0.05), respectively. Additionally, the Lec-AmB-L-Psome showed significantly higher splenic parasite inhibition (78.66 ± 3.08%) compared to Fungizone and Ambisome that caused only 56.54 ± 3.91% (p < 0.05) and 66.46 ± 2.08% (p < 0.05) parasite inhibition, respectively, in Leishmania-infected hamsters. The toxicity profile revealed that Lec-AmB-L-Psome is a safe delivery system with diminished nephrotoxicity which is a limiting factor of Fungizone application. Taken together, these studies suggest that this surface functionalized self-assembled Lec-AmB-L-Psome can introduce a new platform to specifically target macrophages for effective management of intramacrophage diseases. PMID:24842628

  9. Application of Direct Agglutination Test (DAT for the Diagnosis and Seroepide-miological Studies of Visceral Leishmaniasis in Iran

    S Charehdar

    2006-08-01

    Full Text Available Visceral leishmaniasis (VL is one of the most important parasitic diseases which is endemic in different parts of Iran. Serological studies were conducted by direct agglutination test (DAT on 12144 human serum samples, collected from four geographical zones of Iran. Sero prevalence, geographical distribution, clinical signs and symptoms for human visceral leishmaniasis based on DAT for the period of 2002 through 2005 were determined. From 516 kala-azar cases detected: 50.6% were from Meshkin-shahr and Moghan districts in Ardabil Province, northwest of Iran and 49.4% were detected from other areas of Iran. In physical examination of seropositive cases, which were detected by DAT with anti-leishmanial antibodies at titers of 1: 3200 to 1: 102400, almost 50% of suspected individuals showed the classical kala-azar signs and symptoms. Predominant signs and symptoms in 233 hospitalized patients with anti-Leishmania antibodies at 1:3200 and higher, were fever (88.0% and splenomegaly (84.5%. Statistically significant difference was found between males (58% and females (42% (P< 0.01. Moreover, 93.6% of the VL patients were < 5 yr of age, and 6.4% were older than 5 yr that this difference was statistically significant (P< 0.01. From 1383 serum samples collected from domestic dogs in the villages that are known as endemic foci of human leishmaniasis, 152 (11.0% were positive by DAT (≥ 1:320. Parasitological and serological examinations that were performed in 30 wild canines showed that 10% of these animals were infected by L. infantum. L. infantum Lon49 is the principal agent of the disease in human as well as animal reservoir hosts in different parts of Iran. For the first time in Iran, L. tropica isolated from both skin lesions in the face and bone marrow aspiration in a HIV+ man who co-infected with VL as well as in an infected dog from Ardabil Province.

  10. Canine-Based Strategies for Prevention and Control of Visceral Leishmaniasis in Brazil

    Ovallos, Fredy G.; Amaku, Marcus; Carrillo, Eugenia; Moreno, Javier; Galati, Eunice A. B.; Lopes, Estela G.; Soares, Rodrigo M.; Ferreira, Fernando

    2016-01-01

    Visceral leishmaniasis (VL) is a zoonosis found worldwide. Its incidence has increased in Brazil in recent years, representing a serious public and animal health problem. The strategies applied in Brazil are questionable and are not sufficient to control the disease. Thus, we have compared the efficacy of some of the currently available strategies focused on dogs to prevent and control zoonotic VL in endemic areas by optimizing a mathematical model. The simulations showed that the elimination of seropositive dogs, the use of insecticide-impregnated dog collars, and the vaccination of dogs significantly contribute to reducing the prevalence of infection in both canines and humans. The use of insecticide-impregnated collars presented the highest level of efficacy mainly because it directly affected the force of infection and vector-dog contact. In addition, when used at a coverage rate of 90%, insecticide-impregnated collar was able to decrease the prevalence of seropositive dogs and humans to zero; moreover, because of the easy application and acceptance by the targeted population, these collars may be considered the most feasible for inclusion in public policies among the three simulated measures. Vaccination and euthanasia were efficacious, but the latter method is strongly criticized on ethical grounds, and both methods present difficulties for inclusion in public policies. When we compared the use of euthanasia and vaccination at coverages of 70 and 90%, respectively, the proportion of infected populations were similar. However, on evaluating the implications of both of these methods, particularly the negative aspects of culling dogs and the proportion of animals protected by vaccination, the latter measure appears to be the better option if the total cost is not significantly higher. The comparison of complications and advantages of different control strategies allows us to analyze the optimal measure and offer strategies to veterinary and public health

  11. Significantly lower anti-Leishmania IgG responses in Sudanese versus Indian visceral leishmaniasis.

    Tapan Bhattacharyya

    2014-02-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL, a widely distributed systemic disease caused by infection with the Leishmania donovani complex (L. donovani and L. infantum, is almost always fatal if symptomatic and untreated. A rapid point-of-care diagnostic test for anti-Leishmania antibodies, the rK39-immunochromatographic test (rK39-ICT, has high sensitivity and specificity in South Asia but is less sensitive in East Africa. One of the underlying reasons may be continent-specific molecular diversity in the rK39 antigen within the L. donovani complex. However, a second reason may be differences in specific IgG anti-Leishmania levels in patients from different geographical regions, either due to variable antigenicity or immunological response. METHODOLOGY/PRINCIPAL FINDINGS: We determined IgG titres of Indian and Sudanese VL patients against whole cell lysates of Indian and Sudanese L. donovani strains. Indian VL patients had significantly higher IgG titres against both L. donovani strains compared to Sudanese VL patients (p<0.0001. Mean reciprocal log10 50% end-point titres (1/log10t50 were i 3.80 and 3.88 for Indian plasma and ii 2.13 and 2.09 for Sudanese plasma against Indian and Sudanese antigen respectively (p<0.0001. Overall, the Indian VL patients therefore showed a 46.8-61.7 -fold higher mean ELISA titre than the Sudanese VL patients. The higher IgG titres occurred in children (<16 years old and adults of either sex from India (mean 1/log10t50: 3.60-4.15 versus Sudan (mean 1/log10t50: 1.88-2.54. The greatest difference in IgG responses was between male Indian and Sudanese VL patients of ≥ 16 years old (mean 1/log10t50: 4.15 versus 1.99 = 144-fold (p<0.0001. CONCLUSIONS/SIGNIFICANCE: Anti-Leishmania IgG responses among VL patients in Sudan were significantly lower than in India; this may be due to chronic malnutrition with Zn(2+ deficiency, or variable antigenicity and capacity to generate IgG responses to Leishmania antigens. Such

  12. Visceral leishmaniasis in Muzaffarpur district, Bihar, India from 1990 to 2008.

    Paritosh Malaviya

    Full Text Available BACKGROUND: Visceral Leishmaniasis (VL is a vector-borne disease transmitted by Phlebotomus argentipes. To understand the VL seasonality, annual and monthly variations of VL incidence and its relationship to meteorological variables, the numbers of VL cases reported in Muzaffarpur district, Bihar, India from 1990 to 2008 were studied. METHODS: Annual VL incidence per 10,000 and the total number of annual VL cases reported at block Community Health Centres (CHC, Public Hospitals or Non-Governmental Organisations (NGO and the number of VL cases per month from 2000 to 2008 as well as the monthly average of cases for 2000-08, 2000-04 and 2005-08 periods along with the monthly averages of temperature, rainfall and relative humidity were plotted. VL Standardised Incidence Ratios per block were computed for the periods of 1990-1993, 1994-1998, 1999-2004 and 2005-2008 and month wise from 2002 to 2008. A negative binomial regression model was used to evaluate the association between meteorological variables and the number of VL cases per month from 2000 to 2008. RESULTS: A total of 68,358 VL cases were reported in Muzaffarpur district from 1990 to 2008, ranging from 1,2481 in 1992 to 1,161 in 2001. The blocks with the highest number of cases shifted from East (1990-98 to West (1999-2008. Monthly averages of cases ranged from 149 to 309, highest peak in March-April and another one in July. Monthly VL incidence was associated positively to rainfall and negatively to relative humidity and the numbers of VL cases in the previous month. INTERPRETATION: The number of cases reported to the public health sector allowed the describing of the spatial distribution and temporal variations in the Muzaffarpur from 1990 to 2008. However, to assess the actual VL burden, as well as the efficacy of the control measures applied in the district, reporting from private practices and NGOs should be encouraged.

  13. Utilizing Remote Sensing to Explore Hydrological and Climatic Factors of Visceral Leishmaniasis in South Sudan

    Kruczkiewicz, A.; Sweeney, A.; Reid, C.; Seaman, J.; Abubakar, A.; Ritmeijer, K.; Jensen, K.; Schroeder, R.; McDonald, K. C.; Lessel, J.; Thomson, M. C.; Elnaiem, D.; Ceccato, P.

    2014-12-01

    Recent epidemics of visceral leishmaniasis (VL) in Sudan and South Sudan (locally known as Kala Azar) have caused an estimated 100,000 deaths and have renewed the impetus for defining the ecological boundaries of this vector borne disease. In the past 30 years outbreaks have occurred cyclically within this country, but recent shifts in endemicity have necessitated a more robust understanding of the drivers of the disease. Previous work (e.g. Gebre-Michael et al., 2004; Ashford & Thomson, 1991; Hoogstraal & Heyneman, 1969) has suggested that the primary biological vector in this region, the female sand fly Phlebotomus orientalis, exhibits sensitivities to environmental and climatic variables. Results of this study showed a relationship between precipitation and inundation during months of the transmission season (April-July) and the number of confirmed cases in the following September-January period. Particular months of the transmission season with below-average precipitation were better indicators of lagged reports of VL than others. During VL epidemics (2009, 2010, 2011) the month of June exhibited below average precipitation. The two largest epidemics (2010, 2011) were associated with years of below average precipitation in the month of April. Inundation during April-July (AMJJ) also exhibited a strong inverse relationship with reported VL cases in the following September- January (SONDJ). This relationship was best explored when comparing the VL case data of a specific medical center to the inundation anomalies. Results are typified by the Lankien Medical Center analysis where below average inundation during April displays an inverse relationship with VL cases in the following SONDJ. Drought may lead to below average inundation, which could allow for soils to maintain their fissures, thus maintaining the sand fly breeding habitat, resulting in a sustained breeding season for the sandflies (Quate, 1964). Above-average precipitation and inundation might have the

  14. Canine-Based Strategies for Prevention and Control of Visceral Leishmaniasis in Brazil.

    Sevá, Anaiá P; Ovallos, Fredy G; Amaku, Marcus; Carrillo, Eugenia; Moreno, Javier; Galati, Eunice A B; Lopes, Estela G; Soares, Rodrigo M; Ferreira, Fernando

    2016-01-01

    Visceral leishmaniasis (VL) is a zoonosis found worldwide. Its incidence has increased in Brazil in recent years, representing a serious public and animal health problem. The strategies applied in Brazil are questionable and are not sufficient to control the disease. Thus, we have compared the efficacy of some of the currently available strategies focused on dogs to prevent and control zoonotic VL in endemic areas by optimizing a mathematical model. The simulations showed that the elimination of seropositive dogs, the use of insecticide-impregnated dog collars, and the vaccination of dogs significantly contribute to reducing the prevalence of infection in both canines and humans. The use of insecticide-impregnated collars presented the highest level of efficacy mainly because it directly affected the force of infection and vector-dog contact. In addition, when used at a coverage rate of 90%, insecticide-impregnated collar was able to decrease the prevalence of seropositive dogs and humans to zero; moreover, because of the easy application and acceptance by the targeted population, these collars may be considered the most feasible for inclusion in public policies among the three simulated measures. Vaccination and euthanasia were efficacious, but the latter method is strongly criticized on ethical grounds, and both methods present difficulties for inclusion in public policies. When we compared the use of euthanasia and vaccination at coverages of 70 and 90%, respectively, the proportion of infected populations were similar. However, on evaluating the implications of both of these methods, particularly the negative aspects of culling dogs and the proportion of animals protected by vaccination, the latter measure appears to be the better option if the total cost is not significantly higher. The comparison of complications and advantages of different control strategies allows us to analyze the optimal measure and offer strategies to veterinary and public health

  15. Application of loop-mediated isothermal amplification assay for the sensitive and rapid diagnosis of visceral leishmaniasis and post-kala-azar dermal leishmaniasis.

    Verma, Sandeep; Avishek, Kumar; Sharma, Vanila; Negi, Narendra Singh; Ramesh, Venkatesh; Salotra, Poonam

    2013-04-01

    Loop-mediated isothermal amplification (LAMP) is at the forefront in the search for innovative diagnostics for rapid and specific amplification of target DNA under isothermal conditions. We have applied LAMP assay using SYBR Green for clear-cut naked eye detection of Leishmania (Leishmania) donovani in 200 clinical samples of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). The assay was positive in 53/55 VL blood samples (sensitivity, 96.4%; 95% confidence interval [CI], 87.7-99%), 15/15 VL bone marrow aspirate samples (sensitivity, 100%; 95% CI, 79.6-100%), 60/62 PKDL tissue biopsy samples (sensitivity, 96.8%; 95% CI, 88.9-99.1%), and 1/68 control samples (specificity, 98.5%; 95% CI, 92.1-99.7%). The assay was specific for L. (L.) donovani, the causative species for VL and negative for L. (L.) infantum, L. (L.) tropica, and L. (L.) major. This is the first comprehensive clinical study demonstrating the applicability of the LAMP assay for a rapid and reliable molecular diagnosis of VL and PKDL. PMID:23433714

  16. Association of Lutzomyia longipalpis (Diptera: Psychodidae population density with climate variables in Montes Claros, an area of American visceral leishmaniasis transmission in the state of Minas Gerais, Brazil

    Érika Monteiro Michalsky

    2009-12-01

    Full Text Available In the present paper, we evaluate the relationship between climate variables and population density of Lutzomyia longipalpis in Montes Claros, an area of active transmission of American visceral leishmaniasis (AVL in Brazil. Entomological captures were performed in 10 selected districts of the city, between September 2002-August 2003. A total of 773 specimens of L. longipalpiswere captured in the period and the population density could be associated with local climate variables (cumulative rainfall, average temperature and relative humidity through a mathematical linear model with a determination coefficient (Rsqr of 0.752. Although based on an oversimplified statistical analysis, as far as the vector is concerned, this approach showed to be potentially useful as a starting point to guide control measures for AVL in Montes Claros.

  17. Genome-wide scan for visceral leishmaniasis in mixed-breed dogs identifies candidate genes involved in T helper cells and macrophage signaling

    We conducted a genome-wide scan for visceral leishmaniasis in mixed-breed dogs from a highly endemic area in Brazil using 149,648 single nucleotide polymorphism (SNP) markers genotyped in 20 cases and 28 controls. Using a mixed model approach, we found two candidate loci on canine autosomes 1 and 2....

  18. Leishmania donovani-reactive Th1- and Th2-like T-cell clones from individuals who have recovered from visceral leishmaniasis

    Kemp, M; Kurtzhals, J A; Bendtzen, K;

    1993-01-01

    Infections in humans by Leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (VL), or in a self-limiting asymptomatic infection. In murine models of the infection employing Leishmania major, the course of the disease can be directed into a VL-like syndrome...

  19. Sensitivity and specificity of the Leishmania OligoC-TesT and NASBA-oligochromatography for diagnosis of visceral leishmaniasis in Kenya

    F.L. Basiye; M. Mbuchi; C. Magiri; G. Kirigi; S. Deborggraeve; G.J. Schoone; A.A. Saad; S. El-Safi; E. Matovu; M.K. Wasunna

    2010-01-01

    OBJECTIVE To estimate the sensitivity and specificity of the OligoC-TesT and nucleic acid sequence-based amplification coupled to oligochromatography (NASBA-OC) for molecular detection of Leishmania in blood from patients with confirmed visceral leishmaniasis (VL) and healthy endemic controls from K

  20. Visceral leishmaniasis and Acquired Immunodeficiency Sydrome (AIDS: case report Leishmaniose visceral e Síndrome da Imunodeficiência Adquirida (SIDA: relato de um caso

    G.M. de C. Viana

    1994-08-01

    Full Text Available This is a case report that describe an association of AIDS, visceral leishmaniasis and probable disseminated tuberculosis. Due to the spread of AIDS in developing areas worldwide this association would be more frequently, seen on subjects from endemic areas where this protozoonosis is prevalent. More than one opportunistic infection related with the endemic diseases of the developing regions can be associated with those immunocompromised patients.Os autores descrevem um caso de associação de leishmaniose visceral, SIDA e provável tuberculose disseminada. Discutem a possibilidade de associação desta protozoonose e infecção pelo vírus da Imunodeficiência Adquirida (VIH principalmente pelo aumento de prevalência de infecção pelo VIH em áreas endêmicas para o calazar. A presença de imunodepressão pelo VIH possibilita manifestações de agentes oportunistas muitas vezes associados e relacionados com as endemias prevalentes nestas regiões de subdesenvolvimento.

  1. Effects of P-MAPA immunomodulator on Toll-like receptor 2, ROS, nitric oxide, MAPKp38 and IKK in PBMC and macrophages from dogs with visceral leishmaniasis.

    Melo, L M; Perosso, J; Almeida, B F M; Silva, K L O; Somenzari, M A; de Lima, V M F

    2014-02-01

    Leishmania (L.) chagasi is the etiologic agent of visceral leishmaniasis (VL) that can be transmitted to humans and dogs. VL in Brazil represents a serious public health problem; therefore, it is important to study new alternatives to treat infected dogs. In dogs, the therapeutic arsenal against canine VL is limited. The immunomodulator protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) improves immunocompetence when the immune system is impaired, but its dependence on Toll-like receptors (TLRs) and the mechanisms involved in immune response remain unclear. The in vitro action of P-MAPA on the expression of TLR2 and TLR4, reactive oxygen species (ROS), nitric oxide (NO) and p38 mitogen-activated protein kinase (p38 MAPK) and IKK phosphorylation was studied in mononuclear cells from peripheral blood and macrophages from healthy and Leishmania-infected dogs. The PBMC or macrophages were isolated and cultured with different concentrations of P-MAPA (20,100 and 200 μg/ml) in a humid environment at 37°C with 5% CO(2). Observation revealed that Leishmania-infected dogs showed a decrease in TLR2 in macrophages compared with healthy dogs and in induction with P-MAPA. ROS were increased in PBMCs from Leishmania spp.-infected dogs compared with healthy dogs and P-MAPA improved ROS production. NO production was increased in culture supernatant from macrophages stimulated by P-MAPA in both healthy and Leishmania spp. infected dogs. Treatment of macrophages from healthy dogs with immunomodulatory P-MAPA induced p38 MAPK and IKK phosphorylation, suggesting signal transduction by this pathway. These findings suggest that P-MAPA has potential as a therapeutic drug in the treatment of canine visceral leishmaniasis. PMID:24374021

  2. The Potential Use of Forensic DNA Methods Applied to Sand Fly Blood Meal Analysis to Identify the Infection Reservoirs of Anthroponotic Visceral Leishmaniasis

    Inbar, Ehud; Lawyer, Philip; Sacks, David; Podini, Daniele

    2016-01-01

    Background In the Indian sub-continent, visceral leishmaniasis (VL), also known as kala azar, is a fatal form of leishmaniasis caused by the kinetoplastid parasite Leishmania donovani and transmitted by the sand fly Phlebotomus argentipes. VL is prevalent in northeast India where it is believed to have an exclusive anthroponotic transmission cycle. There are four distinct cohorts of L. donovani exposed individuals who can potentially serve as infection reservoirs: patients with active disease, cured VL cases, patients with post kala azar dermal leishmaniasis (PKDL), and asymptomatic individuals. The relative contribution of each group to sustaining the transmission cycle of VL is not known. Methodology/Principal Findings To answer this critical epidemiological question, we have addressed the feasibility of an approach that would use forensic DNA methods to recover human DNA profiles from the blood meals of infected sand flies that would then be matched to reference DNA sampled from individuals living or working in the vicinity of the sand fly collections. We found that the ability to obtain readable human DNA fingerprints from sand flies depended entirely on the size of the blood meal and the kinetics of its digestion. Useable profiles were obtained from most flies within the first 24 hours post blood meal (PBM), with a sharp decline at 48 hours and no readable profiles at 72 hours. This early time frame necessitated development of a sensitive, nested-PCR method compatible with detecting L. donovani within a fresh, 24 hours blood meal in flies fed on infected hamsters. Conclusion/Significance Our findings establish the feasibility of the forensic DNA method to directly trace the human source of an infected blood meal, with constraints imposed by the requirement that the flies be recovered for analysis within 24 hours of their infective feed. PMID:27192489

  3. The TLR2 and TLR4 gene polymorphisms in Moroccan visceral leishmaniasis patients.

    Ejghal, Rajaâ; Hida, Moustapha; Bennani, Mounya Lahkim; Meziane, Mariame; Aurag, Rabia; Lemrani, Meryem

    2016-06-01

    Visceral leishmaniasis (VL) is endemic in the Mediterranean basin and leads to the most severe form of Leishmania infection, lethal if left untreated. However, most infections are sub-clinical or asymptomatic, reflecting the influence of host genetic background on disease outcome. This study aimed to investigate possible association of TLR4 Asp299Gly, TLR4 Thr399Ile and TLR2 Arg753Gln polymorphisms with VL in Moroccan children. We enrolled 119 children with VL caused by Leishmania infantum as well as 138 unrelated children, 95 asymptomatic subjects and 43 healthy individuals who had no evidence of present or past infection. Polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system assay (ARMS-PCR). Results showed significant differences in genotype Thr399Ile and recessive model frequencies between VL and delayed-type hypersensitivity (DTH+) groups (p=0.018, OR=0.414CI 0.195-0.880; p=0.029, OR=0.448CI 0.214-0.938], respectively) by having the amino-acid threonine polymorphism as a reference in the VL group. Concerning the Asp299Gly there were a significant associations when comparing VL vs DTH+ (Asp299Gly genotype p=0.002, OR=0.326CI 0.158-0.671, allele frequencies p=0.033, OR=0.396CI 0.164-0.959, recessive model p=0.002, OR=0.343CI 0.172-0.681) and DTH+ vs DTH- groups (Asp299Gly genotype p=2.160E-4, OR=3.065CI 1.672-5.618, Gly299Gly genotype p=0.047, OR=0.368CI 0.299-0.452, allele frequencies p=1.406E-7, OR=29.571CI 3.907-223.8, recessive model p=4.370E-14, OR=36.965CI 8.629-158.3), by having the aspartic acid polymorphism as a reference these results suggest that the allele A (savage) confer protection against the clinical manifestations but not against the infection. Furthermore, there was a significant association regarding the Arg753Gln genotype (p=0.002, OR=0.326CI 0.158-0.671), allele frequencies (p=0.033, OR=0.396CI 0.164-0.959) and when applying a recessive

  4. Comparison of molecular methods for visceral leishmaniasis diagnosis in asymptomatic dogs

    Visceral Leishmaniasis (VL) is a serious public health problem in Brazil. In the urban area dog is the main source of infection and VL control in Brazil involves the elimination of infected dogs. Serological tests are used for routine surveys, but they present problems of specificity and sensitivity. In addition, serologic test performance depends on infection status and an important limitation in VL control programs is the inability to identify asymptomatic dogs because these tests are insufficiently sensitive. Molecular methods as the kPCR PCR - hybridization are useful in the diagnosis and identification of Leishmania species. The kDNA PCR - hybridization uses radioactive probes to improve the sensibility of the PCR and allow the discrimination between Leishmania species. The aim of this work was compare the sensibility of the method kDNA PCR - Hybridization with different PCR methods, in different clinical samples, for VL diagnosis in asymptomatic animals. Bone marrow, peripheral blood, conjunctival swab and skin biopsies had been analyzed by the methods kDNA PCR - hybridization, kDNA semi nested PCR (kDNA snPCR), Leishmania nested PCR (LnPCR) e Internal Transcribed Spacer 1 nested PCR (ITS-1 nPCR). Thirty positive asymptomatic dogs with positive serologic and parasitologic tests were used. Six not infected dogs had been used as controls. The DNA extraction from swabs was performed by Phenol-Chloroform method. Commercial kits had been used for DNA extraction of peripheral blood, bone marrow and skin biopsies. The kDNA PCR - hybridization detected 5/30 (16.7 %) positive dogs for peripheral blood, 17/30 (57%) for skin, 19/30 (63.3 %) for bone marrow and 21/30 (70%) for conjunctival swab. The kDNA snPCR found 7/30 (23.3%) positive dogs for peripheral blood, 17/30 (57%) for skin, 12/30 (40%) for bone marrow and 24/30 (80%) samples of conjunctival swab. The LnPCR method detected 9/30 (30%) positive dogs for the samples of peripheral blood, 15/30 (50%) for bone

  5. Comparison of molecular methods for visceral leishmaniasis diagnosis in asymptomatic dogs

    Carregal, Virginia M.; Leite, Rodrigo S.; Andrade, Antero S.R., E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Lab. de Radiobiologia; Melo, Maria N., E-mail: melo@icb.ufmg.br [Universidade Federal de Minas Gerais (ICB/UFMG), Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Parasitologia

    2011-07-01

    Visceral Leishmaniasis (VL) is a serious public health problem in Brazil. In the urban area dog is the main source of infection and VL control in Brazil involves the elimination of infected dogs. Serological tests are used for routine surveys, but they present problems of specificity and sensitivity. In addition, serologic test performance depends on infection status and an important limitation in VL control programs is the inability to identify asymptomatic dogs because these tests are insufficiently sensitive. Molecular methods as the kPCR PCR - hybridization are useful in the diagnosis and identification of Leishmania species. The kDNA PCR - hybridization uses radioactive probes to improve the sensibility of the PCR and allow the discrimination between Leishmania species. The aim of this work was compare the sensibility of the method kDNA PCR - Hybridization with different PCR methods, in different clinical samples, for VL diagnosis in asymptomatic animals. Bone marrow, peripheral blood, conjunctival swab and skin biopsies had been analyzed by the methods kDNA PCR - hybridization, kDNA semi nested PCR (kDNA snPCR), Leishmania nested PCR (LnPCR) e Internal Transcribed Spacer 1 nested PCR (ITS-1 nPCR). Thirty positive asymptomatic dogs with positive serologic and parasitologic tests were used. Six not infected dogs had been used as controls. The DNA extraction from swabs was performed by Phenol-Chloroform method. Commercial kits had been used for DNA extraction of peripheral blood, bone marrow and skin biopsies. The kDNA PCR - hybridization detected 5/30 (16.7 %) positive dogs for peripheral blood, 17/30 (57%) for skin, 19/30 (63.3 %) for bone marrow and 21/30 (70%) for conjunctival swab. The kDNA snPCR found 7/30 (23.3%) positive dogs for peripheral blood, 17/30 (57%) for skin, 12/30 (40%) for bone marrow and 24/30 (80%) samples of conjunctival swab. The LnPCR method detected 9/30 (30%) positive dogs for the samples of peripheral blood, 15/30 (50%) for bone

  6. T cells, adhesion molecules and modulation of apoptosis in visceral leishmaniasis glomerulonephritis

    Goto Hiro

    2010-05-01

    Full Text Available Abstract Background Immune complex deposition is the accepted mechanism of pathogenesis of VL glomerulopathy however other immune elements may participate. Further in the present study, no difference was seen between immunoglobulin and C3b deposit intensity in glomeruli between infected and non-infected dogs thus T cells, adhesion molecules and parameters of proliferation and apoptosis were analysed in dogs with naturally acquired VL from an endemic area. The dog is the most important domestic reservoir of the protozoa Leishmania (L. chagasi that causes visceral leishmaniasis (VL. The similarity of VL manifestation in humans and dogs renders the study of canine VL nephropathy of interest with regard to human pathology. Methods From 55 dogs with VL and 8 control non-infected dogs from an endemic area, kidney samples were analyzed by immunohistochemistry for immunoglobulin and C3b deposits, staining for CD4+ and CD8+ T cells, ICAM-1, P-selectin and quantified using morphometry. Besides proliferation marker Ki-67, apoptosis markers M30 and TUNEL staining, and related cytokines TNF-α, IL-1α were searched and quantified. Results We observed similar IgG, IgM and IgA and C3b deposit intensity in dogs with VL and non-infected control dogs. However we detected the Leishmania antigen in cells in glomeruli in 54, CD4+ T cells in the glomeruli of 44, and CD8+ T cells in 17 of a total of 55 dogs with VL. Leishmania antigen was absent and T cells were absent/scarse in eight non-infected control dogs. CD 4+ T cells predominate in proliferative patterns of glomerulonephritis, however the presence of CD4+ and CD8+ T cells were not different in intensity in different patterns of glomerulonephritis. The expression of ICAM-1 and P-selectin was significantly greater in the glomeruli of infected dogs than in control dogs. In all patterns of glomerulonephritis the expression of ICAM-1 ranged from minimum to moderately severe and P-selectin from absent to severe. In

  7. Towards Identifying Immunogenic Targets in Visceral Leishmaniasis: Role of 17kDa and 63kDa Phosphoproteins

    Shubhankar K Singh

    2005-01-01

    Full Text Available We observed predominant phosphorylation at Protein Kinase C (PKC-α residue in seven immunoreactive proteins of virulent Leishmania donovani parasites. These phosphoproteins were tested for their ability to stimulate T-cells for secretion of Macrophage Migration Inhibition Factor (MIF in comparision to crude soluble antigen in Visceral Leishmaniasis (VL patients. Two of these phosphorylated L. donovani antigens led Leishmania to present these antigens to Th1 cells, which was obvious from an increased MIF response. These phosphorylated antigens i. e. 63kDa and 17kDa further led to reprogramme CD4 cells for enhanced IFN-γ production. The study suggests that PKC-phosphoryalation in L. donovani antigens can play a critical role in modulation of signal transduction pathway in T-cells to differentiate into Th1 effectors.

  8. Increased level of soluble adenosine deaminase in bone marrow of visceral leishmaniasis patients: an inverse relation with parasite load.

    Rai, Ambak K; Kumar, Prabin; Saini, Sheetal; Thakur, Chandreshwar P; Seth, Tulika; Mitra, Dipendra K

    2016-09-01

    Adenosine deaminase (ADA) which degrades adenosine to inosine, is known to be pro-inflammatory molecule in many diseases. Adenosine suppresses the functioning of the immune system and thus promotes dissemination of the parasite. In our previous finding, the level of soluble ADA in serum of visceral leishmaniasis (VL) was found to be increased as compared to healthy controls. However, it cannot be fairly interpreted unless their level is demonstrated at the disease site, where the parasite resides. We designed this study to correlate the level of soluble ADA (sADA) with parasitic load at the disease site i.e. bone marrow (BM). We found increased levels of sADA in BM as compared to the unaffected BM. Furthermore, a significant inverse correlation is observed between the parasite load and level of sADA at the disease site. PMID:27447233

  9. Avaliação da leishmaniose visceral canina em Poxoréo, Estado do Mato Grosso, Brazil Canine visceral leishmaniasis evaluation in Poxoréo, Mato Grosso State, Brazil

    Márcia Ávila A. de Azevedo

    2008-09-01

    Full Text Available O cão doméstico desempenha importante papel como reservatório na transmissão da leishmaniose visceral ao homem, zoonose de grande importância em saúde pública. Realizou-se avaliação epidemiológica da leishmaniose visceral em 1.112 cães domiciliados no município de Poxoréo, estado do Mato Grosso e observou-se prevalência de 7,8%. Observou-se ainda associação estatisticamente significativa entre a prevalência de leishmaniose visceral canina e as variáveis faixa etária, presença de sinais clínicos e presença de outra espécie animal co-habitando com os cães avaliados, tendo sido as galinhas mais freqüentemente observadas entre os animais soropositivos. O sexo, a coleta de lixo domiciliar bem como a renda familiar não apresentaram associação estatisticamente significativa com a prevalência da leishmaniose visceral canina. A análise dos resultados sugere que cães com idade superior a sete anos e a , presença de outra espécie animal co-habitando com os cães podem ser fatores de risco para a leishmaniose visceral canina.Dogs play an important role as reservoir in the domestic cycle of visceral leishmaniasis, a serious public health problem. An epidemiological survey in 1,112 dogs was conducted at the Municipality of Poxoréo State of Mato Grosso, Brazil, using indirect immunofluorescence antibody test where the prevalence was 7.8%. Significant association was found between prevalence of canine visceral leishmaniasis and age of the dogs. Clinical signs and presence of other animals in the backyard, like chicken being more likely associated with seropositivity. Gender, garbage collection in the residence and family financial income were not associated with visceral leishmaniasis prevalence. Analysis of the results suggests that dogs aging more than 7 years and presence of another animal species co-inhabiting with the dogs may be risk factors for canine visceral leishmaniasis.

  10. Immunogenicity of HSP-70, KMP-11 and PFR-2 leishmanial antigens in the experimental model of canine visceral leishmaniasis.

    Carrillo, Eugenia; Crusat, Martín; Nieto, Javier; Chicharro, Carmen; Thomas, Maria del Carmen; Martínez, Enrique; Valladares, Basilio; Cañavate, Carmen; Requena, Jose María; López, Manuel Carlos; Alvar, Jorge; Moreno, Javier

    2008-03-28

    Zoonotic visceral leishmaniasis (ZVL) is a parasitic disease caused by Leishmania infantum/L. chagasi that is emerging as an important medical and veterinary problem. Dogs are the domestic reservoir for this parasite and, therefore, the main target for controlling the transmission to humans. In the present work, we have evaluated the immunogenicity of the Leishmania infantum heat shock protein (HSP)-70, paraflagellar rod protein (PFR)-2 and kinetoplastida membrane protein (KMP)-11 recombinant proteins in dogs experimentally infected with the parasite. We have shown that peripheral blood mononuclear cells (PBMC) from experimentally infected dogs proliferated in response to these recombinant antigens and against the soluble leishmanial antigen (SLA). We have also quantified the mRNA expression level of the cytokines induced in PBMC upon stimulation with the HSP-70, PFR-2 and KMP-11 proteins. These recombinant proteins induced an up-regulation of IFN-gamma. HSP-70 and PFR-2 also produced an increase of the TNF-alpha transcripts abundance. No measurable induction of IL-10 was observed and low levels of IL-4 mRNA were produced in response to the three mentioned recombinant antigens. Serum levels of specific antibodies against HSP-70, PFR-2 and KMP-11 recombinant proteins were also determined in these animals. Our study showed that HSP-70, KMP-11 and PFR-2 proteins are recognized by infected canines. Furthermore, these antigens produce a Th1-type immune response, suggesting that they may be involved in protection. The identification as vaccine candidates of Leishmania antigens that elicit appropriate immune responses in the canine model is a key step in the rational approach to generate a vaccine for canine visceral leishmaniasis. PMID:18321614

  11. Larval breeding sites of Lutzomyia longipalpis (Diptera: Psychodidae in visceral leishmaniasis endemic urban areas in Southeastern Brazil.

    Cláudio Casanova

    Full Text Available BACKGROUND: The scarcity of information on the immature stages of sand flies and their preferred breeding sites has resulted in the focus of vectorial control on the adult stage using residual insecticide house-spraying. This strategy, along with the treatment of human cases and the euthanasia of infected dogs, has proven inefficient and visceral leishmaniasis continues to expand in Brazil. Identifying the breeding sites of sand flies is essential to the understanding of the vector's population dynamic and could be used to develop novel control strategies. METHODOLOGY/PRINCIPAL FINDING: In the present study, an intensive search for the breeding sites of Lutzomyia longipalpis was conducted in urban and peri-urban areas of two municipalities, Promissão and Dracena, which are endemic for visceral leishmaniasis in São Paulo State, Brazil. During an exploratory period, a total of 962 soil emergence traps were used to investigate possible peridomiciliary breeding site microhabitats such as: leaf litter under tree, chicken sheds, other animal sheds and uncovered debris. A total of 160 sand flies were collected and 148 (92.5% were L. longipalpis. In Promissão the proportion of chicken sheds positive was significantly higher than in leaf litter under trees. Chicken shed microhabitats presented the highest density of L. longipalpis in both municipalities: 17.29 and 5.71 individuals per square meter sampled in Promissão and Dracena respectively. A contagious spatial distribution pattern of L. longipalpis was identified in the emergence traps located in the chicken sheds. CONCLUSION: The results indicate that chicken sheds are the preferential breeding site for L. longipalpis in the present study areas. Thus, control measures targeting the immature stages in chicken sheds could have a great effect on reducing the number of adult flies and consequently the transmission rate of Leishmania (Leishmania infantum chagasi.

  12. Comparative B-mode and Doppler renal ultrasonography with histopathological findings in dogs positive for canine visceral leishmaniasis.

    Baltazar, Pollyana Irene; Da Silva Moura, Laecio; Pessoa, Gerson Tavares; De Sá Rodrigues, Renan Paraguassu; Sanches, Marina Pinto; Das Neves Diniz, Anaemilia; Das Chagas Araújo Sousa, Francisco; Guerra, Porfírio Candanedo; Neves, Willams Costa; Giglio, Robson Fortes; De Jesus Rosa Pereira Alves, Jacyara; De Assis Leite Souza, Francisco; Braga, Juliana Fortes Vilarinho; Alves, Flávio Ribeiro

    2016-07-01

    Morphological parameters and renal flow were assessed and measured in six clinically healthy dogs with negative serological and parasitological examinations for canine visceral leishmaniasis (CVL) and six dogs with CVL-positive serological and parasitological tests and asymptomatic condition of the disease. Kidney length and diameter were measured and compared with the aorta/kidney ratio. Alterations in flow were measured using the flow velocity (cm/s) and resistance index (RI). Renal function was assessed by serum biochemical examination (urea, creatine, total proteins, albumin, and globulin) and urinalysis. CVL-positive animals presented heterogeneous kidney echotexture, reduced vascular flow, hypoperfusion, lesser visualization of the arcuate arteries, high RI values (1.06 ± 0.28 for the right kidney and 1.10 ± 0.30 for the left kidney), reduced diastolic flow, and high systolic peak. They also presented positive creatine/RI correlation and between the renal artery vascular flow and kidney diameter. Histopathological analysis of CVL-positive animals was compatible and confirmed hemodynamic changes observed by Doppler ultrasound. The findings in the present study showed that Doppler ultrasonography is a valid method to assess and detect alterations in flow in renal pathological processes with kidney vascular damage, as in the case of leishmaniasis, and can help in the diagnosis of animals with this infection. Microsc. Res. Tech. 79:637-645, 2016. © 2016 Wiley Periodicals, Inc. PMID:27194210

  13. Canine Visceral Leishmaniasis in Rio de Janeiro, Brazil: clinical, parasitological, therapeutical and epidemiological findings (1977-1983

    Mauro C. A. Marzochi

    1985-09-01

    Full Text Available Forty dogs from the periphery of the city of Rio de Janeiro were studied. All dogs where diagnosed as positive for leishmaniasis either parasitologically and/or serologically. Among them, 19 came from areas where only Visceral Leishmaniasis (VL occurs (Realengo, Bangu, Senador Camará. Clinical signs of the disease were seen in 36.8% of the cases, including emaciation - 100%, lymphadenopathy and depilation - 85.7%. The other 21 dogs came from an area (Campo Grande where both diseases (VL, and American Cutaneous Leishmaniasis - ACL occur. Clinical signs of the disease, mainly cutaneous or mucocutaneous ulcers were seen in 76.2% of the cases. Leishmania parasites were found in 39 cases: 22% in viscera, 42.5% in viscera and normal skin and 35% in cutaneous or mucocutaneous ulcers. All the Leishmania stocks isolated from dogs which came from Realengo, Bangu, Senador Camará (VL area, and from Campo Grande (VL + ACL area were characterized as L. donovani (except in one case according to their schizodeme, zymodeme and serodeme. The only stock characterized as L. b. braziliensis, was isolated from the lymph node of a dog from Campo Grande with visceral disease and without skin lesions. Antimony therapy attempted in eight Leishmania donovani positive dogs was unsuccessful.Durante inquéritos caninos realizados na periferia da cidade do Rio de Janeiro, foram estudados clínica e laboratorialmente 40 cães. Todos apresentavam diagnóstico parasitológico e/ou sorológico de leishmaniose. Dentre esses, 19 procediam de áreas de ocorrência de leishmaniose visceral (LV - Realengo, Bangu e Senador Camará. Sinais clínicos sugestivos da infecção foram observados em 36,8% deles (incluindo emagrecimento - 100%, linfadenopatia e depilação - 85,7%. Outros 21 cães procediam da área de Campo Grande onde tanto a LV como a leishmaniose tegumentar americana (LTA ocorrem. Sinais clínicos da infecção por Leishmania, principalmente ulcerações cutâneas e

  14. Leishmaniasis.

    Moore, Elinor M; Lockwood, Diana N

    2011-10-01

    Leishmaniasis is an uncommon infectious disease in the UK with a variety of clinical presentations. Physicians should remember to consider this diagnosis in patients with an appropriate travel history (including the Mediterranean basin) and seek help with diagnostics from a specialised parasitology laboratory. Treatment regimens may be unfamiliar to the general physician, and thus should also be discussed with an expert. PMID:22034715

  15. Characterization and speculations on the urbanization of visceral leishmaniasis in Brazil Caracterização e especulações acerca da urbanização da leishmaniose visceral no Brasil

    Carlos Henrique Nery Costa

    2008-01-01

    The available hypotheses or explanations for the urbanization of American visceral leishmaniasis are insufficient. An alternative hypothesis is that changes in the ecology and biology of the vector, Lutzomyia longipalpis, might explain all the new urban epidemiological features of the disease. To tackle the knowledge gaps in this process, certain key research areas need to be prioritized: the role of dogs in expanding transmission in cities, community trials to evaluate new insecticides, and ...

  16. Natural Leishmania infantum infection in Migonemyia migonei (França, 1920) (Diptera:Psychodidae:Phlebotominae) the putative vector of visceral leishmaniasis in Pernambuco State, Brazil.

    de Carvalho, Maria Rosimery; Valença, Helio França; da Silva, Fernando José; de Pita-Pereira, Daniela; de Araújo Pereira, Thaís; Britto, Constança; Brazil, Reginaldo Peçanha; Brandão Filho, Sinval Pinto

    2010-10-01

    A study of the natural infection of phlebotomine sand flies by Leishmania (Leishmania) infantum was conducted in an area of visceral leishmaniasis in São Vicente Férrer, located in the northern part of the Atlantic rain forest region in the State of Pernambuco, Brazil. In a previous study, Migonemyia migonei have been found predominantly in peridomiciles and houses in this endemic area. The analysis of M. migonei, collected by CDC light trap, by multiplex PCR assay coupled to non-isotopic hybridization showed that 2 females out of 50 were infected by L. infantum. This is the first finding of natural infection of M. migonei by L. infantum suggesting that M. migonei may be the vector of L. infantum in areas of visceral leishmaniasis where Lutzomyia longipalpis, the usual vector, is absent. PMID:20457120

  17. Chemical and environmental vector control as a contribution to the elimination of visceral leishmaniasis on the Indian subcontinent: cluster randomized controlled trials in Bangladesh, India and Nepal

    Das Pradeep; Kumar Vijay; Mondal Dinesh; Chowdhury Rajib; Akhter Shireen; Das Murari L; Joshi Anand B; Kroeger Axel; Boelaert Marleen; Petzold Max

    2009-01-01

    Abstract Background Bangladesh, India and Nepal are working towards the elimination of visceral leishmaniasis (VL) by 2015. In 2005 the World Health Organization/Training in Tropical Diseases launched an implementation research programme to support integrated vector management for the elimination of VL from Bangladesh, India and Nepal. The programme is conducted in different phases, from proof-of-concept to scaling up intervention. This study was designed in order to evaluate the efficacy of ...

  18. Cloning and characterization of a V-ATPase subunit C from the American visceral leishmaniasis vector Lutzomyia longipalpis modulated during development and blood ingestion

    Ramalho-Ortigão JM; AN Pitaluga; EL Telleria; Marques, C.; Souza AA de; YM Traub-Cseko

    2007-01-01

    Visceral leishmaniasis (VL) is a serious tropical disease that affects approximately 500 thousand people worldwide every year. In the Americas, VL is caused by the parasite Leishmania (Leishmania) infantum chagasi mainly transmitted by the bite of the sand fly vector Lutzomyia longipalpis. Despite recent advances in the study of interaction between Leishmania and sand flies, very little is known about sand fly protein expression profiles. Understanding how the expression of proteins may be af...

  19. Visceral and cutaneous leishmaniasis in urban area of cartagena: a case report

    Pinzón-Redondo Hernando; Orta-López Carlos; Pérez-Yapes Carlos; Juliao-Cardona Lucía; Agamez-De Ávila Issa; Matorel-Bello Eliana; Miranda-Moncada Yasmira; Torres-Figueroa Camilo

    2012-01-01

    Introduction: Leishmaniasis is a disease caused by protozoan parasites that belongto the genus Leishmania. It is characterized by a chronic course, involving the skin andmucous membranes or viscera depending on the causative specie and host immune response.Its highest prevalence is in tropical rural areas, but constant incursions of men into theecological niche of the vectors involved as hosts and adaptation of some species to newhabitats, could bring a change in the incidence of the disease....

  20. Vaccines for Canine Leishmaniasis

    Faeze Foroughi-Parvar

    2014-01-01

    Full Text Available Leishmania infantum is the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL. The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now.

  1. Diagnosis of visceral Leishmaniasis in asymptomatic dogs by the KDNA PCR-hybridization assay using noninvasive samples

    Leite, Rodrigo Souza; Andrade, Antero Silva Ribeiro de [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Lab. de Radiobiologia], e-mail: rleite2005@gmail.com; Ferreira, Sydney de Almeida; Ituassu, Leonardo Trindade; Melo, Maria Norma de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Centro de Ciencias Biologicas. Dept. de Parasitologia], e-mail: saninoalmeida@gmail.com

    2009-07-01

    The visceral leishmaniasis (VL) in Brazil is caused by Leishmania (Leishmania) chagasi and the asymptomatic dogs may transmit the parasite to sand flies vectors. The VL epidemiological control in Brazil involves the elimination of seropositive dogs, insecticide treatment and systematic treatment of human cases. Therefore, the accurate diagnosis is important in order to avoid the disease transmission or unnecessary culling of dogs. Serological tests are used for screening of dogs. However, these techniques present limitations. The Polymerase Chain Reaction (PCR) is an attractive alternative to the diagnosis in this context; but non-invasive samplings have great importance because they are simpler, painless and less resisted by dog-owners. This study aimed at evaluating conjunctival swab (CS) for canine VL diagnosis. In this methodology a sterile cotton swab is used to sampling the dog conjunctiva in both eyes. Thirty asymptomatic seropositive dogs were used. The samples were analyzed by the kDNA PCR-hybridization procedure in which the PCR products are hybridized with cloned kDNA mini-circles labeled with {sup 32}P[]dCTP. In addition, blood (B) was collected from each animal. L. chagasi was identified in 90% of CS samples and 13,6% of B samples. The high sensitivity obtained with asymptomatic dogs, in which the diagnosis is more difficult due the low number of parasites in the samples, allow concluding that the conjunctival swab associated to the kDNA PCR-hybridization assay provides a valuable alternative tool for the direct diagnosis of canine leishmaniasis. (author)

  2. Diagnosis of visceral Leishmaniasis in asymptomatic dogs by the KDNA PCR-hybridization assay using noninvasive samples

    The visceral leishmaniasis (VL) in Brazil is caused by Leishmania (Leishmania) chagasi and the asymptomatic dogs may transmit the parasite to sand flies vectors. The VL epidemiological control in Brazil involves the elimination of seropositive dogs, insecticide treatment and systematic treatment of human cases. Therefore, the accurate diagnosis is important in order to avoid the disease transmission or unnecessary culling of dogs. Serological tests are used for screening of dogs. However, these techniques present limitations. The Polymerase Chain Reaction (PCR) is an attractive alternative to the diagnosis in this context; but non-invasive samplings have great importance because they are simpler, painless and less resisted by dog-owners. This study aimed at evaluating conjunctival swab (CS) for canine VL diagnosis. In this methodology a sterile cotton swab is used to sampling the dog conjunctiva in both eyes. Thirty asymptomatic seropositive dogs were used. The samples were analyzed by the kDNA PCR-hybridization procedure in which the PCR products are hybridized with cloned kDNA mini-circles labeled with 32P[]dCTP. In addition, blood (B) was collected from each animal. L. chagasi was identified in 90% of CS samples and 13,6% of B samples. The high sensitivity obtained with asymptomatic dogs, in which the diagnosis is more difficult due the low number of parasites in the samples, allow concluding that the conjunctival swab associated to the kDNA PCR-hybridization assay provides a valuable alternative tool for the direct diagnosis of canine leishmaniasis. (author)

  3. Comparative study of rK39 Leishmania antigen for serodiagnosis of visceral leishmaniasis: systematic review with meta-analysis.

    Zuinara Maia

    2012-01-01

    Full Text Available BACKGROUND: The rK39 recombinant protein is derived from a specific antigen produced by the Leishmania donovani complex, and has been used in the last two decades for the serodiagnosis of visceral leishmaniasis. We present here a systematic review and meta-analysis of studies evaluating serologic assays to diagnose visceral leishmaniasis to determine the accuracy of rK39 antigen in comparison to the use of other antigen preparations. METHODOLOGY/PRINCIPAL FINDINGS: A systematic review with meta-analysis of the literature was performed to compare the rK39 strip-test and ELISA formats against serological tests using promastigote antigens derived from whole or soluble parasites for Direct Aglutination Test (DAT, Indirect Immunofluorescence test (IFAT and ELISA with a promastigote antigen preparation (p-ELISA. Gold standard diagnosis was defined by the demonstration of amastigotes on hematological specimens. A database search was performed on Medline, Lilacs, Scopus, Isi Web of Science, and Cochrane Library. Quality of data was assessed using the QUADAS questionnaire. A search of the electronic databases found 352 papers of which only 14 fulfilled the selection criteria. Three evaluated the rK39 ELISA, while 13 evaluated the rK39 immunochromatographic strip test. The summarized sensitivity for the rK39-ELISA was 92% followed by IFAT 88% and p-ELISA 87%. The summarized specificity for the three diagnostic tests was 81%, 90%, and 77%. Studies comparing the rK39 strip test with DAT found a similar sensitivity of 94%, although the DAT had a slightly higher specificity. The rK39 strip test was more sensitive and specific than the IFAT and p-ELISA. We did not detect any difference in the sensitivity and specificity between strips produced by different manufacturers. CONCLUSIONS: The rK39 protein used either in a strip test or in an ELISA, and the DAT are the best choices for implementation of rapid, easy and efficient test for serodiagnosis of VL.

  4. Nível sérico da vitamina A em crianças portadoras de leishmaniose visceral Vitamin A serum level in children with visceral leishmaniasis

    Kleber Giovanni Luz

    2001-01-01

    Full Text Available A vitamina A tem sido considerada uma vitamina anti-infecciosa e sua deficiência está associada a um maior risco de infecções graves, como ocorre por exemplo no sarampo. Nos países em desenvolvimento a hipovitaminose A é um grave problema de saúde pública. O objetivo deste estudo é quantificar o nível sérico da vitamina A em pacientes pediátricos portadores da leismaniose visceral (LV. Amostras de sangue foram coletadas de 22 crianças portadoras de LV, estocadas em freezer e posteriormente, quantificado o nível de vitamina A usando-se a cromatrografia líquída de alta eficiência, nove irmãos assintomáticos dos pacientes foram usados como controles. A média do nível sérico da vitamina A nos portadores de LV foi de 21,38µg/100ml e no grupo controle foi de 31,39µg/100ml. Entre os pacientes estudados com LV a média do nível sérico de vitamina A encontrado foi significativamente menor, utilizando-se o teste t de Student para um pVitamin A is considered an anti-infectious disease vitamin, and its deficiency is associated with severe infections such as in measles. In developing countries the low concentrations of vitamin A are a public health problem. The aim of this study is to describe serum vitamin A concentrations among children with visceral leishmaniasis (VL. Blood sample was collected from 22 children with VL, and stored in a freezer, 9 siblings, with no clinical signs of the VL patients had their blood collected for a control group. Samples were assayed by high performance liquid chromatography. The median vitamin A concentration in the LV group was 21.38µg/100ml and in the control group it was 31.39µg/100. The mean in the LV was statistically lower than in the control group, using Student's t test, p<0.01.

  5. Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis Expressão de citocinas na mucosa duodenal de pacientes com leishmaniose visceral

    Kleber Giovanni Luz

    2010-08-01

    Full Text Available INTRODUCTION: Visceral leishmaniasis (VL is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p INTRODUÇÃO: Leishmaniose visceral (LV é uma doença tropical negligenciada com uma resposta imune complexa em diferentes órgãos. Este padrão de resposta imune órgão-específica nunca foi avaliada no trato gastrointestinal. O objetivo deste estudo foi determinar a resposta imune in situ em biópsias duodenais de pacientes com LV. MÉTODOS: Um estudo de caso controle com 13 pacientes com LV foi comparado com 9 controles. A resposta imune foi avaliada por imunohistoquímica para CD4, CD8, CD68, IL-4, IFN-γ, TNF-α e IL-10. Achados histológicos nos vilos, criptas e processo inflamatório foram analisados. RESULTADOS: Todos os casos de LV apresentaram antígenos de Leishmania. Nenhum antígeno foi encontrado no grupo controle. O tamanho do vilo foi maior em pacientes com LV (p < 0,05. CD68 (macrófagos e CD4 estavam aumentados em pacientes com LV (p < 0,05. Nenhuma diferença foi demonstrada na expressão de CD8, TNF-α, IL-10 e IL-4. O número de células expressando IFN-γ foi mais baixo que no grupo controle (p < 0,05. CONCLUSÕES: Baixos níveis de citocinas foram encontrados no trato gastrointestinal de pacientes com LV. Este padrão não foi encontrado em

  6. A current perspective on leishmaniasis

    Angela Clem

    2010-01-01

    Full Text Available There are many challenges facing the successful control and eradication of cutaneous and visceral leishmaniasis. Leishmaniasis is still endemic in many poverty stricken and war torn areas. Through the use of an extensive literature review, this article examined the global disease burden of cutaneous and visceral leishmaniasis. Surveillance and control measures for leishmaniasis being used by the World Health Organization were also discussed in this article. Finally, potential new treatments and possible vaccines for leishmaniasis were reviewed in this article.

  7. Leishmaniasis in rheumatoid arthritis

    Cutolo, M; M.E. Secchi; C. Pizzorni

    2011-01-01

    Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis is of higher priority than cutaneous leishmaniasis as it is a fatal disease in the absence of treatment. The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well establishe...

  8. Sand fly salivary proteins induce strong cellular immunity in a natural reservoir of visceral leishmaniasis with adverse consequences for Leishmania.

    Collin, Nicolas; Gomes, Regis; Teixeira, Clarissa; Cheng, Lily; Laughinghouse, Andre; Ward, Jerrold M; Elnaiem, Dia-Eldin; Fischer, Laurent; Valenzuela, Jesus G; Kamhawi, Shaden

    2009-05-01

    Immunity to a sand fly salivary protein protects against visceral leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-gamma at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG(2) antibody levels and significant IFN-gamma production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the bite site characterized by lymphocytic infiltration and IFN-gamma and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response. PMID:19461875

  9. Local Production of a Liquid Direct Agglutination Test as a Sustainable Measure for Control of Visceral Leishmaniasis in Sudan.

    Osman, Hussam Ali; Mahamoud, Abdelhafeiz; Abass, Elfadil Mustafa; Madi, Rubens Riscala; Semiao-Santos, Saul J; El Harith, Abdallah

    2016-05-01

    A prerequisite for the control of visceral leishmaniasis (VL) is the accessibility to reference diagnostics. The high price of the freeze-dried direct agglutination test (FD-DAT) and the short shelf-life time of the rK39 strip test (rK39) have limited the application of these tests in Sudan. An original liquid DAT (LQ-DAT) with high reproducibility compared with the FD-DAT and rK39 has been routinely produced in our laboratory since 1999. In this study, a 3.4-year-old batch (of more than 90 test batches produced to date) was chosen to validate the diagnostic performance of this test against microscopy, FD-DAT, and rK39 in 96 VL and 42 non-VL serum samples. Relatively higher sensitivity (95/96, 99.0%) was recorded for the LQ-DAT than for the FD-DAT (92/96, 95.8%) and rK39 (76/96, 79.2%), probably because of the use of the endemic autochthonous Leishmania donovani isolate as the antigen. Experience with the LQ-DAT, its low cost of production, ease of providing this test, and diagnostic reliability compared with the FD-DAT suggest that widescale implementation of the LQ-DAT can contribute to sustainable VL control in Sudan. PMID:26976890

  10. A prototype of the direct agglutination test kit (DAT-Canis) for the serological diagnosis of canine visceral leishmaniasis.

    Oliveira, Edward; Saliba, Juliana Wilke; Oliveira, Diana; Dias, Edelberto Santos; Paz, Gustavo Fontes

    2016-05-15

    This report describes the stege I/II development of a new direct agglutination test (DAT) for the diagnosis of canine visceral leishmaniasis (CVL) using freeze-dried antigen produced Coomassie blue-stained Leishmania (Leishmania) infantum promastigotes. In stage I, 16 canine serum samples, collected from eight dogs carrying CVL and eight healthy dogs, were assessed with the DAT using 2-mercaptoethanol (2-ME), N-acetyl-cysteine (NAC), kaolin or NAC plus urea (NAC+U) to improve the assay conditions. Stage II assessed the diagnostic accuracy with 100 serum samples collected from dogs with symptomatic CVL and clinically healthy dogs, comparing the four different sample diluents. The CVL-DAT prototype kit showed equivalent performances when 2-ME, NAC or NAC+U were used: 97.1% sensitivity (CI: 83-99.8%), 97% specificity (CI: 88.5-99.5%) and a 97% diagnostic accuracy (CI: 90.8-99.2). With kaolin, a 94.1% sensitivity (CI: 79-99%), 97% specificity (CI: 88.5-99.5%) and 96% diagnostic accuracy were observed (CI: 89.5-98.7), with no statistically significant differences among the four reagents (p=1.0). The NAC plus urea in sample diluent decreased non-specific agglutination, promoted a better defined sharp-edged blue spot and was thus chosen as a component for the new DAT prototype to diagnose canine VL, designated DAT-Canis. PMID:27084465

  11. The value of a new microculture method for diagnosis of visceral leishmaniasis by using bone marrow and peripheral blood.

    Allahverdiyev, Adil M; Bagirova, Malahat; Uzun, Soner; Alabaz, Derya; Aksaray, Necmi; Kocabas, Emine; Koksal, Fatih

    2005-08-01

    We have demonstrated that the microculture method (MCM) enables the diagnosis of visceral leishmaniasis (VL) with samples from both the bone marrow (BM) and peripheral blood (PB). The MCM is superior to the traditional culture method (TCM) as determined by its higher sensitivity in the detection of promastigotes and the more rapid time for emergence of promastigotes. The sensitivity of MCM (100% in BMs and 77.8-100% in PB) was considerably higher than that of the TCM (37.5-100% in BMs and 0-100% in PB) according to decreasing parasite density (P < 0.05). The concentration of parasites in buffy coats has increased the sensitivity of both methods, especially that of the MCM. Detection of promastigotes by MCM requires lower amounts of culture media (25-50 microL) and shorter incubation periods (2-7 days) than TCM (2.5-3.5 mL and 15-35 days, respectively). MCM was found to be valuable with the advantages of simplicity and sensitivity, in addition to being cost-effective in the routine diagnosis for VL in Adana Turkey. PMID:16103589

  12. Lutzomyia longipalpis and the eco-epidemiology of American visceral leishmaniasis, with particular reference to Brazil: a review

    Ralph Lainson

    2005-12-01

    Full Text Available An historical review is given of American visceral leishmaniasis (AVL, with particular reference to the eco-epidemiology of the disease in Brazil. Following the first records of AVL in this country, in 1934, the sandfly Lutzomyia longipalpis (Lutz and Neiva, 1912 was incriminated as the principal vector. It is now generally accepted, however, that there exist a number of cryptic species under the name of Lu. longipalpis s.l. and that variations in the quantity of the vasodilatory peptide maxadilan in the saliva of flies from different populations of Lu. longipalpis s.l., may account for the variable clinical manifestations of AVL seen in different geographic regions. Distribution of AVL has been shown to extend throughout most of South and Central America, with the domestic dog serving as the principal reservoir of infection for man. However, while one hypothesis suggests that the causative parasite is Leishmania infantum, imported from Europe with the Portuguese and Spanish colonists, the demonstration of a high rate of benign, inapparent infection in foxes in Amazonian Brazil raised an opposing suggestion that the parasite is indigenous to the Americas. Recent reports of similar infections in native marsupials, and possibly rodents, tend to support this view, particularly as Lu. longipalpis is primordially a silvatic sandfly. Although effective control measures in foci of the disease will diminish the number of canine and human infections, the presence of such an enzootic in a variety of native animals will render the total eradication of AVL unlikely.

  13. Insecticide susceptibility status of Phlebotomus argentipes, a vector of visceral leishmaniasis in different foci in three states of India

    R.K. Singh, P.K. Mittal & R.C. Dhiman

    2012-12-01

    Full Text Available Background & objectives: Phlebotomus argentipes is the vector for visceral leishmaniasis in India. Thedevelopment of resistance in kala-azar vector to DDT has been reported from various parts of India. The mainobjective of this study was to generate information on insecticides susceptibility status of P. argentipes to DDT,malathion and deltamethrin in different parts in three states of India.Methods: Phlebotomus argentipes were collected from different villages, identified and used to investigate thesusceptibility status against DDT, malathion and deltamethrin as per the WHO standard methods.Results: Phlebotomus argentipes was resistant to DDT in different areas, viz. PHCs Murumgaon in Maharashtra;Ramgarh in Jharkhand; Kodah, Falka, Mahua and Lalganj in Bihar. In Phulwari Shareef PHC of Patna districtin Bihar, DDT produced 89% mortality in P. argentipes, indicating resistant/tolerance (verification required toDDT. The corrected percent mortality to malathion (5% in different areas ranged between 98 and 100%; and todeltamethrin (0.05% between 98.4 and 100%. The results showed that the tested P. argentipes are susceptibleto malathion and deltamethrin.Conclusion: Phlebotomus argentipes are still susceptible to malathion and deltamethrin, but resistant to DDT.The susceptibility status of P. argentipes should be monitored regularly in diversified situations to ascertain thejudicious use of insecticides being used for indoor residual spraying in the programme for rational use ofappropriate insecticide.

  14. Polymerase chain reaction of peripheral blood as a tool for the diagnosis of visceral leishmaniasis in children

    Thiago Leite Fraga

    2010-05-01

    Full Text Available The diagnosis of visceral leishmaniasis (VL generally requires the use of invasive tests for the collection of infected tissue (aspirates of bone marrow, spleen, liver or lymph nodes. This difficulty has led to the search for safer and less painful techniques to confirm the occurrence of the disease in children. Polymerase chain reaction (PCR is a method that is advantageous in that it allows the use of peripheral blood samples for diagnosis. This paper reports the utilisation of PCR on peripheral blood samples to diagnose VL in 45 children in Mato Grosso do Sul, Brazil. This technique is compared with methods carried out using tissue collected by invasive procedures, including direct microscopy, culture and detection of Leishmania DNA by PCR in bone marrow aspirates. The results show that PCR of peripheral blood provides great sensitivity (95.6% that is similar to that from the PCR of bone marrow aspirates (91.1% and higher than that achieved with microscopy (80% or culture (26.7% methods. PCR of peripheral blood proved to be a suitable tool for the diagnosis of VL in children because it is highly sensitive and safe, with tissue collection being less invasive than in traditional tests.

  15. Biotic factors and occurrence of Lutzomyia longipalpis in endemic area of visceral leishmaniasis, Mato Grosso do Sul, Brazil

    Everton Falcão de Oliveira

    2012-05-01

    Full Text Available The relationships between environmental exposure to risk agents and health conditions have been studied with the aid of remote sensing imagery, a tool particularly useful in the study of vegetation cover. This study aims to evaluate the influence of environmental variables on the spatial distribution of the abundance of Lutzomyia longipalpis and the reported canine and human visceral leishmaniasis (VL cases at an urban area of Campo Grande, state of Mato Grosso do Sul. The sandfly captures were performed in 13 residences that were selected by raffle considering four residences or collection station for buffer. These buffers were generated from the central house with about 50, 100 and 200 m from it in an endemic area of VL. The abundance of sandflies and human and canine cases were georreferenced using the GIS software PCI Geomatica. The normalized difference vegetation index (NDVI and percentage of land covered by vegetation were the environmental variables extracted from a remote sensing IKONOS-2 image. The average NDVI was considered as the complexity of habitat and the standard deviation as the heterogeneity of habitat. One thousand three hundred sixty-seven specimens were collected during the catch. We found a significant positive linear correlation between the abundance of sandflies and the percentage of vegetation cover and average NDVI. However, there was no significant association between habitat heterogeneity and the abundance of these flies.

  16. Leishmania (Leishmania chagasi-infected mice as a model for the study of glomerular lesions in visceral leishmaniasis

    M.G. Prianti

    2007-06-01

    Full Text Available Renal involvement in visceral leishmaniasis (VL is very frequent but the pathogenesis of this nephropathy is poorly understood. In previous studies using dogs with VL we have detected new immunopathological elements in the glomeruli such as T cells and adhesion molecules. Although Leishmania (Leishmania chagasi-infected dogs and hamsters are considered to be good models for VL, their use is limited for immunopathologic studies. The use of isogenic mouse strains susceptible to L. (L. chagasi infection was an alternative but, on the other hand, the renal lesions of these animals have not yet been characterized. Thus, our purpose in the present study was to characterize mice infected with L. (L. chagasi as a suitable model to study VL nephropathy. Kidney samples were obtained from control mice (N = 12 and from BALB/c mice (N = 24 injected intraperitoneally with 20 million L. (L. chagasi amastigotes 7, 15, and 30 days after injection and processed for histopathological studies and detection of IgG deposits. Glomerular hypercellularity was clearly visible and, upon Mason's trichrome and periodic acid methenamine silver staining, a pattern suggestive of mesangial proliferative glomerulonephritis was observed in mice with VL. Time-dependent IgG deposits were also seen in infected mice. We consider L. (L. chagasi-infected mice to be a suitable model for studies of the immunopathogenesis of glomerular lesions in VL.

  17. Diagnosing visceral leishmaniasis and HIV/AIDS co-infection: a case series study in Pernambuco, Brazil

    Aracele Tenório de Almeida e Cavalcanti

    2012-02-01

    Full Text Available HIV/AIDS-associated visceral leishmaniasis may display the characteristics of an aggressive disease or without specific symptoms at all, thus making diagnosis difficult. The present study describes the results of diagnostic tests applied to a series of suspected VL cases in HIV-infected/AIDS patients admitted in referral hospitals in Pernambuco, Brazil. From a total of 14 eligible patients with cytopenias and/or fever of an unknown etiology, and indication of bone marrow aspirate, 10 patients were selected for inclusion in the study. Diagnosis was confirmed by the following examinations: Leishmania detection in bone marrow aspirate, direct agglutination test, indirect immunofluorescence, rK39 dipstick test, polymerase chain reaction and latex agglutination test. Five out of the ten patients were diagnosed with co-infection. A positive direct agglutination test was recorded for all five co-infected patients, the Leishmania detection and latex agglutination tests were positive in four patients, the rK39 dipstick test in three, the indirect immunofluorescence in two and a positive polymerase chain reaction was recorded for one patient. This series of cases was the first to be conducted in Brazil using this set of tests in order to detect co-infection. However, no consensus has thus far been reached regarding the most appropriate examination for the screening and monitoring of this group of patients.

  18. Sand fly salivary proteins induce strong cellular immunity in a natural reservoir of visceral leishmaniasis with adverse consequences for Leishmania.

    Nicolas Collin

    2009-05-01

    Full Text Available Immunity to a sand fly salivary protein protects against visceral leishmaniasis (VL in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-gamma at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG(2 antibody levels and significant IFN-gamma production following in vitro stimulation of PBMC with salivary gland homogenate (SGH. Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the bite site characterized by lymphocytic infiltration and IFN-gamma and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response.

  19. An rK28-Based Immunoenzymatic Assay for the Diagnosis of Canine Visceral Leishmaniasis in Latin America.

    Lauricella, Marta Alicia; Maidana, Cristina Graciela; Frias, Victoria Fragueiro; Romagosa, Carlo M; Negri, Vanesa; Benedetti, Ruben; Sinagra, Angel J; Luna, Concepcion; Tartaglino, Lilian; Laucella, Susana; Reed, Steven G; Riarte, Adelina R

    2016-07-01

    Direct observation of Leishmania parasites in tissue aspirates has shown low sensitivity for the detection of canine visceral leishmaniasis (VL). Therefore in the last quarter century immunoenzymatic tests have been developed to improve diagnosis. The purpose of this study was to develop a fast recombinant K28 antigen, naked-eye qualitative enzyme-linked immunosorbent assay (VL Ql-ELISA) and a quantitative version (VL Qt-ELISA), and to display it in a kit format, whose cutoff value (0.156) was selected as the most adequate one to differentiate reactive from nonreactive samples. Considering 167 cases and 300 controls, sensitivity was 91% for both assays and specificity was 100% and 98.7% in Ql-ELISA and Qt-ELISA, respectively. Positive predictive values were 100% and 97.4% for Ql-ELISA and Qt-ELISA, respectively, and negative predictive values were 95.2% for both ELISAs. Reagent stability, reliability studies, including periodic repetitions and retest of samples, cutoff selection, and comparison of rK28 ELISAs with rK39 immunochromatographic test, were the international criteria that supported the quality in both kits. The performance of both ELISA kits in this work confirmed their validity and emphasized their usefulness for low-to-medium complexity laboratories. PMID:27162270

  20. Phenology and population dynamics of sand flies in a new focus of visceral leishmaniasis in Eastern Azarbaijan Province, North western of Iran

    Teimour Hazratian; Yavar Rassi; Mohammad Ali Oshaghi; Mohammad Reza Yaghoobi-Ershadi; Esmael Fallah; Mohammad Reza Shirzadi; Sina Rafizadeh

    2011-01-01

    Objective:To investigate species composition, density, accumulated degree-day and diversity of sand flies during April to October2010in Azarshahr district, a new focus of visceral leishmaniasis in north western Iran.Methods: Sand flies were collected using sticky traps biweekly and were stored in96% ethanol. All specimens were mounted in Puri's medium for species identification using valid keys of sandflies. The density was calculated by the formula: number of specimens/m2 of sticky traps and number of specimens/ number of traps. Degree-day was calculated as follows: (Maximum temperature + Minimum temperature)/2-Minimum threshold. Diversity indices of the collected sand flies within different villages were estimated by s the Shannon- weaver formula (H'=ΣPilogePi i=1 ).Results:Totally5 557 specimens comprising 16Species (14Phlebotomus, and 2Sergentomyia) were indentified. The activity of the species extended from April to October. Common sand-flies in resting places werePhlebotomus papatasi, Phlebotomus sergenti andPhlebotomus mongolensis. The monthly average density was 37.6, 41.1, 40.23, 30.38 and30.67 for Almalodash, Jaragil, Segaiesh, Amirdizaj and Germezgol villages, respectively. Accumulated degree-day from early January to late May was approximately289 degree days. The minimum threshold temperature for calculating of accumulated degree-day was17.32℃. According on the Shannon-weaver (H'), diversity of sand flies within area study were estimated as0.917, 1.867, 1.339, 1.673, and1.562in Almalodash, Jaragil, Segaiesh, Amirdizaj and Germezgol villages, respectively.Conclusions: This study is the first detailed research in terms of species composition, density, accumulated degree-day and diversity of sand flies in an endemic focus of visceral leishamaniasis in Azarshahr district. The population dynamics of sand flies in Azarshahr district were greatly affected by climatic factors. According to this study the highest activity of the collected sand fly species

  1. A Novel Sterol Isolated from a Plant Used by Mayan Traditional Healers Is Effective in Treatment of Visceral Leishmaniasis Caused by Leishmania donovani.

    Gupta, Gaurav; Peine, Kevin J; Abdelhamid, Dalia; Snider, Heidi; Shelton, Andrew B; Rao, Latha; Kotha, Sainath R; Huntsman, Andrew C; Varikuti, Sanjay; Oghumu, Steve; Naman, C Benjamin; Pan, Li; Parinandi, Narasimham L; Papenfuss, Tracy L; Kinghorn, A Douglas; Bachelder, Eric M; Ainslie, Kristy M; Fuchs, James R; Satoskar, Abhay R

    2015-10-01

    Visceral leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani, is a global health problem affecting millions of people worldwide. Treatment of VL largely depends on therapeutic drugs such as pentavalent antimonials, amphotericin B, and others, which have major drawbacks due to drug resistance, toxicity, and high cost. In this study, for the first time, we have successfully demonstrated the synthesis and antileishmanial activity of the novel sterol pentalinonsterol (PEN), which occurs naturally in the root of a Mexican medicinal plant, Pentalinon andrieuxii. In the experimental BALB/c mouse model of VL induced by infection with L. donovani, intravenous treatment with liposome-encapsulated PEN (2.5 mg/kg) led to a significant reduction in parasite burden in the liver and spleen. Furthermore, infected mice treated with liposomal PEN showed a strong host-protective TH1 immune response characterized by IFN-γ production and formation of matured hepatic granulomas. These results indicate that PEN could be developed as a novel drug against VL. PMID:27623316

  2. Research Progress on the Diagnosis Technology of Canine Visceral Leishmaniasis%犬内脏利什曼病诊断方法的研究进展

    丁丹; 汪俊云

    2012-01-01

    Canine visceral leishmaniasis is caused by Leishmania infantum. Infected dogs, either symptomatic or asymptomatic, are considered as the major reservoirs for zoonotic viscera] leishmaniasis. Accurate and rapid detection of canine leishmanial infection is crucial for control of human visceral leishmaniasis due to its role in the transmission of the infection to vectors. Various techniques based on parasitology, immunology and molecular biology have been studied and evaluated for detecting canine leishmanial infection. This article reviews the progress in techniques and methods for its diagnosis.%犬内脏利什曼病由婴儿利什曼原虫(Leishmania infantum)感染引起,病犬和无症状感染犬是动物源型内脏利什曼病流行区人内脏利什曼病的主要传染源.对犬内脏利什曼病的诊断是控制动物源型内脏利什曼病的关键,应高度重视诊断方法的研究.本文就犬内脏利什曼病诊断方法的研究进展作一综述.

  3. Rapid diagnosis and genotyping of Leishmania isolates from cutaneous and visceral leishmaniasis by microcapillary cultivation and polymerase chain reaction-restriction fragment length polymorphism of miniexon region.

    Serin, Mehmet S; Daglioglu, Kenan; Bagirova, Melahat; Allahverdiyev, Adil; Uzun, Soner; Vural, Zeynep; Kayar, Begum; Tezcan, Seda; Yetkin, Mesut; Aslan, Gonul; Emekdas, Gurol; Koksal, Fatih

    2005-11-01

    We have performed a combination of microcapillary cultivation method and restriction fragment length polymorphism (RFLP) analysis of amplified products by 1 single PCR of miniexon region of Leishmania for molecular diagnosis and genotyping of different Leishmania species isolated from cutaneous leishmaniasis (CL) and visceral leishmaniasis. We have analyzed 10 microcapillary cultivated isolates from cutaneous cases and 5 microcapillary cultivated isolates from visceral cases (totally 15) by polymerase chain reaction-RFLP (PCR-RFLP). Of 10 isolates, 3 (30%) were genotyped as Leishmania infantum and 7 (70%) of 10 isolates were genotyped as Leishmania tropica from the microcapillary cultivated isolates of cutaneous cases. On the other hand, all 5 isolates (100%) were genotyped as L. infantum from microcapillary cultivated visceral cases. Our most interesting finding is the presence of 3 L. infantum isolates in CL cases without kala-azar history. Therefore, we suggest that further investigations must be done about this subject. On the other hand, we suggest the combination of microcapillary culture method and PCR-RFLP of miniexon region of leishmaniae can be used in routine laboratory experimentation because of their simple, cheap, and rapid benefits (within a week), whereas other different approaches offer a multitude of valid taxonomic characters for species identification. PMID:16249065

  4. Metagenomic analysis of taxa associated with Lutzomyia longipalpis, vector of visceral leishmaniasis, using an unbiased high-throughput approach.

    Christina B McCarthy

    2011-09-01

    Full Text Available BACKGROUND: Leishmaniasis is one of the most diverse and complex of all vector-borne diseases worldwide. It is caused by parasites of the genus Leishmania, obligate intramacrophage protists characterised by diversity and complexity. Its most severe form is visceral leishmaniasis (VL, a systemic disease that is fatal if left untreated. In Latin America VL is caused by Leishmania infantum chagasi and transmitted by Lutzomyia longipalpis. This phlebotomine sandfly is only found in the New World, from Mexico to Argentina. In South America, migration and urbanisation have largely contributed to the increase of VL as a public health problem. Moreover, the first VL outbreak was recently reported in Argentina, which has already caused 7 deaths and 83 reported cases. METHODOLOGY/PRINCIPAL FINDINGS: An inventory of the microbiota associated with insect vectors, especially of wild specimens, would aid in the development of novel strategies for controlling insect vectors. Given the recent VL outbreak in Argentina and the compelling need to develop appropriate control strategies, this study focused on wild male and female Lu. longipalpis from an Argentine endemic (Posadas, Misiones and a Brazilian non-endemic (Lapinha Cave, Minas Gerais VL location. Previous studies on wild and laboratory reared female Lu. longipalpis have described gut bacteria using standard bacteriological methods. In this study, total RNA was extracted from the insects and submitted to high-throughput pyrosequencing. The analysis revealed the presence of sequences from bacteria, fungi, protist parasites, plants and metazoans. CONCLUSIONS/SIGNIFICANCE: This is the first time an unbiased and comprehensive metagenomic approach has been used to survey taxa associated with an infectious disease vector. The identification of gregarines suggested they are a possible efficient control method under natural conditions. Ongoing studies are determining the significance of the associated taxa found

  5. PHLEBOTOMUS (LARROUSSIUS KESHISHIANI HCHURENKOVA 1936, ANOTHER VECTOR OF VISCERAL LEISHMANIASIS IN IRAN

    M.A. Seyedi Rashti

    1995-08-01

    Full Text Available In a sand-fly survey, conducted for two years (1992-93 in GhirKarzjn, Fars province a total of 1020 female Phlebotomus keshishiani were dissected, of which 12 females were found to have promastigotes. Promastigotes of six Pb. keshishiani were inoculated to six hamsters and one hamster became infected, Amastigotes were observed in the spleen, but the culture of parasite was not possible due to death of the hamster. Of 141 blood meals tested, 28.5% and 57.7% of Ph. keshishiani were fed on human and dog respectively. This is the first report in the world about the role of Pb. keshishiani as a probable vector of thinfantile type of visceral leishmanjasis.

  6. Visceral Leishmaniasis in Benishangul-Gumuz Regional State, Western Ethiopia: Reemerging or Emerging?

    Abera, Adugna; Tasew, Geremew; Tsegaw, Teshome; Kejella, Asfaw; Mulugeta, Abate; Worku, Dagimlidet; Aseffa, Abraham; Gadisa, Endalamaw

    2016-07-01

    Kala-azar is a growing public health problem in Ethiopia. Benishangul-Gumuz regional state was previously not known to be endemic for the disease. In response to a case report from the region, we conducted a rapid assessment survey. A pretested questionnaire was used to capture sociodemographic and clinical histories pertinent to kala-azar. Study participants with complaints of fever and headache for 2 weeks or more were tested for kala-azar and malaria. All participants were screened with the leishmanin skin test and the direct agglutination test for exposure to Leishmania, defined as a positive result with either or both tests. Of 275 participants, 20 were exposed giving an overall leishmaniasis seroprevalence rate of 7.3%. Among the 20 positive individuals, 19 were farmers and nine of them reported no travel history outside their district. It appears that kala-azar is emerging in Dangur and Guba districts of Benishangul-Gumuz regional state, probably in connection with human encroachment into one or several previously out-of-reach zoonotic foci. We recommend integrated epidemiological surveys for confirmation and early containment of disease transmission in the area. PMID:27139445

  7. Pneumocystis carinii pneumonia, pulmonary tuberculosis and visceral leishmaniasis in an adult HIV negative patient

    Antonio Carlos Toledo Jr.

    2001-06-01

    Full Text Available This is a case report of a 29 year old male with pneumocystis pneumonia and tuberculosis, and who was initially suspected of having HIV infection, based on risk factor analyses, but was subsequently shown to be HIV negative. The patient arrived at the hospital with fever, cough, weight loss, loss of appetite, pallor, and arthralgia. In addition, he was jaundiced and had cervical lymphadenopathy and mild heptosplenomegaly. He had interstitial infiltrates of the lung, sputum smears positive for Mycobacterium tuberculosis and Pneumocystis carinii, and stool tests were positive for Strongyloides stercoralis and Schistosoma mansoni. He was diagnosed as having AIDS, and was treated for tuberculosis, pneumocystosis, and strongyloidiasis with a good response. The patient did not receive anti-retroviral therapy, pending outcome of the HIV tests. A month later, he was re-examined and found to have worsening hepatosplenomegaly, pancytopenia, fever, and continued weight loss. At this time, it was determined that his HIV ELISA antibody tests were negative. A bone marrow aspirate was done and revealed amastigotes of leishmania, and a bone marrow culture was positive for Leishmania species. He was treated with pentavalent antimony, 20 mg daily for 20 days, with complete remission of symptoms and weight gain. This case demonstrates that immunosuppression from leishmaniasis and tuberculosis may lead to pneumocystosis, and be misdiagnosed as HIV infection. The occurrence of opportunistic infections in severely ill patients without HIV must always be considered and alternate causes of immunosuppression sought.

  8. Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

    Bhowmick Sudipta

    2010-06-01

    Full Text Available Abstract Background The development of an effective vaccine against visceral leishmaniasis (VL caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG and Monophosphoryl lipid A (MPL plus trehalose dicorynomycolate (TDM with cationic liposomes, in combination with LAg, to confer protection against murine VL. Results All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. Conclusion This comparative study reveals greater effectiveness of the liposomal vaccine for

  9. Clinical Forms of Canine Visceral Leishmaniasis in Naturally Leishmania infantum–Infected Dogs and Related Myelogram and Hemogram Changes

    Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Reis, Levi Eduardo Soares; Carvalho, Maria das Graças; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Bouillet, Leoneide Erica Maduro; Lemos, Denise Silveira; Coura-Vital, Wendel; Reis, Alexandre Barbosa

    2013-01-01

    Hematological analysis has limited applications for disease diagnosis in Leishmania infantum–infected dogs, but it can be very important in evaluating the clinical forms of the disease and in understanding the evolution of canine visceral leishmaniasis (CVL) pathogenesis. Recently, we demonstrated that alterations in leucopoiesis and erythropoiesis are related to clinical status and bone marrow parasite density in dogs naturally infected by L. infantum. To further characterize these alterations, we evaluated the association between the hematological parameters in bone marrow and peripheral blood alterations in groups of L. infantum–infected dogs: asymptomatic I (AD-I: serum negative/PCR+), asymptomatic II (AD-II: serum positive), oligosymptomatic (OD), and symptomatic (SD). Results were compared with those from noninfected dogs (NID). The SD group was found to present a decrease in erythropoietic lineage with concomitant reductions in erythrocytes, hemoglobin, and hematocrit parameters, resulting in anemia. The SD group also had increased neutrophils and precursors and decreased band eosinophils and eosinophils, leading to peripheral blood leucopenia. In the AD-II group, lymphocytosis occurred in both the peripheral blood and the bone marrow compartments. The SD group exhibited lymphocytosis in the bone marrow, with lymphopenia in the peripheral blood. In contrast, the AD-I group, showed no significant changes suggestive of CVL, presenting normal counts in bone marrow and peripheral blood. Our results showed for the first time that important changes in hematopoiesis and hematological parameters occur during ongoing CVL in naturally infected dogs, mainly in symptomatic disease. Taken together, our results based on myelogram and hemogram parameters enable better understanding of the pathogenesis of the anemia, lymphocytosis, and lymphopenia, as well as the leucopenia (eosinopenia and monocytopenia), that contribute to CVL prognosis. PMID:24376612

  10. Incidence of visceral leishmaniasis in the Vaishali district of Bihar, India: spatial patterns and role of inland water bodies

    Gouri Sankar Bhunia

    2011-05-01

    Full Text Available The role of the distribution of inland water bodies with respect to the transmission of visceral leishmaniasis (VL and its dominant vector, Phlebotomous argentipes, has been studied at the regional scale in Bihar, eastern India. The Landsat TM sensor multispectral scanning radiometer, with a spatial resolution of 30 m in the visible, reflective-infrared and shortwave- infrared (SWIR bands, was used to identify water bodies using the normalized differential pond index (NDPI calculated as follows: (Green – SWIR I/(Green + SWIR I. Nearest neighbour and grid square statistics were used to delineate spatial patterns and distribution of the sandfly vector and the disease it transmits. The female P. argentipes sandfly was found to be associated with the distance from open water and particularly abundant near non-perennial river banks (68.4%; P <0.001, while its association with rivers was focused further away from the water source (X2 = 26.3; P <0.001. The results also reveal that the distribution of VL is clustered around non-perennial riverbanks, while the pattern is slightly random around the perennial river banks. The grid square technique illustrate that the spatial distribution of the disease has a much stronger correlation with lower density of open waters surfaces as well as with sandfly densities (X2 = 26.0; P <0.001. The results of our study suggest that inland water presence poses a risk for VL by offering suitable breeding sites for P. argentipes, a fact that should be taken into account when attempting to control disease transmission.

  11. An outbreak investigation of visceral leishmaniasis among residents of Dharan town, eastern Nepal, evidence for urban transmission of Leishmania donovani

    Uranw Surendra

    2013-01-01

    Full Text Available Abstract Background Visceral leishmaniasis (VL is a predominantly rural disease, common in the low lands of eastern Nepal. Since 1997 VL cases have also been reported among residents of the city of Dharan. Our main research objective was to find out whether there had been local transmission of VL inside the city. Methods We conducted an outbreak investigation including a case–control study; cases were all urban residents treated for VL between 2000 and 2008 at BP Koirala Institute of Health Sciences, a university hospital in the city. For each case, we selected four random controls, with no history of previous VL; frequency-matched for age. Cases and controls were subjected to a structured interview on the main exposures of interest and potential confounders; a binominal multilevel model was used to analyze the data. We also collected entomological data from all neighborhoods of the city. Results We enrolled 115 VL patients and 448 controls. Cases were strongly clustered, 70% residing in 3 out of 19 neighborhoods. We found a strong association with socio-economic status, the poorest being most at risk. Housing was a risk factor independent from socio-economic status, most at risk were those living in thatched houses without windows. ‘Sleeping upstairs’ and ‘sleeping on a bed’ were strongly protective, OR of 0.08 and 0.25 respectively; proximity to a case was a strong risk factor (OR 3.79. Sand flies were captured in all neighborhoods; in collections from several neighborhoods presence of L. donovani could be demonstrated by PCR. Conclusion The evidence found in this study is consistent with transmission of anthroponotic VL within the city. The vector P. argentipes and the parasite L. donovani have both been identified inside the town. These findings are highly relevant for policy makers; in VL endemic areas appropriate surveillance and disease control measures must be adopted not only in rural areas but in urban areas as well.

  12. Knowledge, attitudes and practices related to visceral leishmaniasis in rural communities of Amhara State: a longitudinal study in northwest Ethiopia.

    Noemí López-Perea

    2014-04-01

    Full Text Available BACKGROUND: In the northwest of Ethiopia, at the South Gondar region, there was a visceral leishmaniasis (VL outbreak in 2005, making the disease a public health concern for the regional health authorities ever since. The knowledge on how the population perceives the disease is essential in order to propose successful control strategies. METHODOLOGY/PRINCIPAL FINDINGS: Two surveys on VL knowledge, attitudes and practices were conducted at the beginning (May 2009 and at the end (February 2011 of a VL longitudinal study carried out in rural communities of Libo Kemkem and Fogera, two districts of the Amhara Regional State. Results showed that VL global knowledge was very low in the area, and that it improved substantially in the period studied. Specifically, from 2009 to 2011, the frequency of proper knowledge regarding VL signs and symptoms increased from 47% to 71% (p<0.0001, knowledge of VL causes increased from 8% to 25% (p<0.0001, and knowledge on VL protection measures from 16% to 55% (p<0.0001. Moreover, the improvement observed in VL knowledge was more marked among the families with no previous history of VL case. Finally, in 2011 more than 90% of the households owned at least an impregnated bed net and had been sprayed, and attitudes towards these and other protective measures were very positive (over 94% acceptance for all of them. CONCLUSIONS/SIGNIFICANCE: In 2009 the level of knowledge regarding VL was very low among the rural population of this area, although it improved substantially in the study period, probably due to the contribution of many actors in the area. VL patients and relatives should be appropriately informed and trained as they may act as successful health community agents. VL risk behavioural patterns are subject to change as attitudes towards protective measures were very positive overall.

  13. High parasitological failure rate of visceral leishmaniasis to sodium stibogluconate among HIV co-infected adults in Ethiopia.

    Ermias Diro

    2014-05-01

    Full Text Available BACKGROUND: Antimonials are still being used for visceral leishmaniasis (VL treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern. OBJECTIVES: This study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG. METHODS: Retrospective patient record analysis of VL-HIV co-infected patients treated at a clinical trial site in north-west Ethiopia was done. Patients with parasitologically confirmed VL and HIV co-infection treated with SSG were included. The dose of SSG used was 20 mg Sb5 (pentavalent antimony/kg and maximum of 850 mg Sb5 for 30 days. The clinical outcomes were defined based on the tissue aspiration results as cure or failure, and additionally the safety and mortality rates were computed. RESULTS: The study included 57 patients treated with SSG and by the end of treatment only 43.9% of patients were cured. The parasitological treatment failure and the case fatality rate were 31.6% and 14.0% respectively. SSG was discontinued temporarily or permanently for 12 (21.1% cases due to safety issues. High baseline parasite load (graded more than 4+ was significantly associated with treatment failure (odds ratio = 8.9, 95% confidence interval = .5-51.7. CONCLUSION: SSG is not only unsafe, but also has low effectiveness for VL-HIV patients. Safe and effective alternative medications are very urgently needed. Drug sensitivity surveillance should be introduced in the region.

  14. Evaluation of parasitological, immunological and DNA based detection methods for the diagnosis of visceral leishmaniasis in Sudan

    Visceral leishmaniasis (V L) is endemic in the Sudan where it poses a major health problem in many parts of the country. This study was designed to evaluate parasitological, immunological and DNA based detection methods for diagnosis of V L in Sudan. Direct agglutination test was performed in sera from V L suspects (n,513) using the trypsin treated antigen DAT.T of sensitivity 89%. Moreover, DAT.T detected V L in 43% of unconfirmed V L cases (P0.05). The detection rate of 2ME-DAT.R and DAT.T, in unconfirmed (n,67), was 46.3% and 40.3%, respectively (P>0.05). The specificity of both DAT antigens, in non-endemic controls (n,200), was 100%. The specificity of both DAT.R and DAT.T, in sera of patient with other diseases (n, 178), was 98.9% and 98.3%, respectively. The sensitivity of 2ME-DAT.R, using specimens of serum, saliva and urine was 100%, 21.7% and 0%, respectively. DAT.R was positive in saliva and sera of 2 unconfirmed V L cases. The sensitivity of slide formol gel test (FGT) was 84.3% in comparison to 89% for DAT.T (P0.05). The detection rate of CIE and DAT.T, was 33% in comparison to 22% by DAT.T. The specificity of CIE and DAT.T was 100%. The sensitivity of cellulose acetate perciptin (CAP) was 33%, while that of DAT.T was 100% (P0.05)

  15. Biomarkers of safety and immune protection for genetically modified live attenuated Leishmania vaccines against visceral leishmaniasis-Discovery and implications

    Sreenivas eGannavaram

    2014-05-01

    Full Text Available Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated

  16. Immunoprotective responses of T helper type 1 stimulatory protein-S-adenosyl-L-homocysteine hydrolase against experimental visceral leishmaniasis.

    Khare, P; Jaiswal, A K; Tripathi, C D P; Sundar, S; Dube, A

    2016-08-01

    It is well known that a patient in clinical remission of visceral leishmaniasis (VL) remains immune to reinfection, which provides a rationale for the feasibility of a vaccine against this deadly disease. In earlier studies, observation of significant cellular responses in treated Leishmania patients as well as in hamsters against leishmanial antigens from different fractions led to its further proteomic characterization, wherein S-adenosyl-L-homocysteine hydrolase (AdoHcy) was identified as a helper type 1 (Th1) stimulatory protein. The present study includes immunological characterization of this protein, its cellular responses [lymphoproliferation, nitric oxide (NO) production and cytokine responses] in treated Leishmania-infected hamsters and patients as well as prophylactic efficacy against Leishmania challenge in hamsters and the immune responses generated thereof. Significantly higher cellular responses were noticed against recombinant L. donovani S-adenosyl-L-homocysteine hydrolase (rLdAdoHcy) compared to soluble L. donovani antigen in treated samples. Moreover, stimulation of peripheral blood mononuclear cells with rLdAdoHcy up-regulated the levels of interferon (IFN)-γ, interleukin (IL)-12 and down-regulated IL-10. Furthermore, vaccination with rLdAdoHcy generated perceptible delayed-type hypersensitivity response and exerted considerably good prophylactic efficacy (∼70% inhibition) against L. donovani challenge. The efficacy was confirmed by the increased expression levels of inducible NO synthase and Th1-type cytokines, IFN-γ and IL-12 and down-regulation of IL-4, IL-10 and transforming growth factor (TGF)-β. The results indicate the potentiality of rLdAdoHcy protein as a suitable vaccine candidate against VL. PMID:26898994

  17. Comparison of kDNA PCR-hybridization assay with three PCR methods for canines visceral Leishmaniasis diagnosis

    The sensitivity of the kDNA PCR-Hybridization assay, which uses radioactive DNA probes (labeled with 32P), was compared with three conventional PCR methods used for canine visceral leishmaniasis diagnosis. All PCR methods had two steps: a first amplification followed by hybridization or by a new amplification (nested or semi nested). Two methods (kDNA PCR-Hybridization and kDNA snPCR) used primers addressed to kinetoplast minicircles and the other two methods to the coding (LnPCR) and intergenic noncoding regions (ITS-1 nPCR) of the ribosomal rRNA genes. The comparison was accomplished in two groups of 23 infected dogs using samples collected by the conjunctival swab procedure. In the Group 1 the DNA was extracted from cotton swabs by phenol-chloroform and in Group 2 by boiling. The most efficient PCR methods in the Group 1 were those based on kDNA targets. The kDNA PCR-Hybridization was able to detect parasites in 22/23 dogs (95.6%) and in 40/46 samples (86.9%). The kDNA snPCR was positive for 21/23 dogs (91.3%) and for 40/46 samples (86.9%). The positivities of the kDNA based methods were significantly higher than the positivities verified for the methods based on ribosomal rRNA genes (p<0.05). In the Group 2 the kDNA PCR- Hybridization showed a better performance detecting parasites in 18/23 dogs (78.3%) and in 31/46 samples (67.4%), significantly higher than the other three methods (p<0.05). The higher sensitivity of the minicircle kDNA based assays reported by others was confirmed in this study and kDNA PCR-Hybridization showed the best sensitivity among the assays evaluated. (author)

  18. Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: a multicentre, open-label, randomized trial.

    Asrat Hailu

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India. METHODS: This was a 3-arm multicentre, open-label, randomized, controlled clinical trial to compare three treatment regimens for VL in East Africa: paromomycin sulphate (PM at 15 mg/kg/day for 21 days versus sodium stibogluconate (SSG at 20 mg/kg/day for 30 days; and the combination of both dose regimens for 17 days. The primary efficacy endpoint was cure based on parasite-free tissue aspirates taken 6 months after treatment. FINDINGS: Overall, 135 patients per arm were enrolled at five centres in Sudan (2 sites, Kenya (1 and Ethiopia (2, when the PM arm had to be discontinued due to poor efficacy. The trial has continued with the higher dose of PM as well as the combination of PM and SSG arms. These results will be reported later. Baseline patient characteristics were similar among treatment arms. The overall cure with PM was significantly inferior to that with SSG (63.8% versus 92.2%; difference 28.5%, 95%CI 18.8% to 38.8%, p<0.001. The efficacy of PM varied among centres and was significantly lower in Sudan (14.3% and 46.7% than in Kenya (80.0% and Ethiopia (75.0% and 96.6%. No major safety issues with PM were identified. CONCLUSION: The efficacy of PM at 15 mg/kg/day for 21 days was inadequate, particularly in Sudan. The efficacy of higher doses and the combination treatment warrant further studies.

  19. Sodium stibogluconate (SSG & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomised controlled trial.

    Ahmed Musa

    Full Text Available BACKGROUND: Alternative treatments for visceral leishmaniasis (VL are required in East Africa. Paromomycin sulphate (PM has been shown to be efficacious for VL treatment in India. METHODS: A multi-centre randomized-controlled trial (RCT to compare efficacy and safety of PM (20 mg/kg/day for 21 days and PM plus sodium stibogluconate (SSG combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days with SSG (20 mg/kg/day for 30 days for treatment of VL in East Africa. Patients aged 4-60 years with parasitologically confirmed VL were enrolled, excluding patients with contraindications. Primary and secondary efficacy outcomes were parasite clearance at 6-months follow-up and end of treatment, respectively. Safety was assessed mainly using adverse event (AE data. FINDINGS: The PM versus SSG comparison enrolled 205 patients per arm with primary efficacy data available for 198 and 200 patients respectively. The SSG & PM versus SSG comparison enrolled 381 and 386 patients per arm respectively, with primary efficacy data available for 359 patients per arm. In Intention-to-Treat complete-case analyses, the efficacy of PM was significantly lower than SSG (84.3% versus 94.1%, difference = 9.7%, 95% confidence interval, CI: 3.6 to 15.7%, p = 0.002. The efficacy of SSG & PM was comparable to SSG (91.4% versus 93.9%, difference = 2.5%, 95% CI: -1.3 to 6.3%, p = 0.198. End of treatment efficacy results were very similar. There were no apparent differences in the safety profile of the three treatment regimens. CONCLUSION: The 17 day SSG & PM combination treatment had a good safety profile and was similar in efficacy to the standard 30 day SSG treatment, suggesting suitability for VL treatment in East Africa. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.govNCT00255567.

  20. Comparison of kDNA PCR-hybridization assay with three PCR methods for canines visceral Leishmaniasis diagnosis

    Pilatti, Marcia M.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)], e-mail: marciapilatti@yahoo.com.br, e-mail: antero@cdtn.br; Ferreira, Sidney A. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Parasitologia], e-mail: saninoalmeida@gmail.com

    2009-07-01

    The sensitivity of the kDNA PCR-Hybridization assay, which uses radioactive DNA probes (labeled with {sup 32}P), was compared with three conventional PCR methods used for canine visceral leishmaniasis diagnosis. All PCR methods had two steps: a first amplification followed by hybridization or by a new amplification (nested or semi nested). Two methods (kDNA PCR-Hybridization and kDNA snPCR) used primers addressed to kinetoplast minicircles and the other two methods to the coding (LnPCR) and intergenic noncoding regions (ITS-1 nPCR) of the ribosomal rRNA genes. The comparison was accomplished in two groups of 23 infected dogs using samples collected by the conjunctival swab procedure. In the Group 1 the DNA was extracted from cotton swabs by phenol-chloroform and in Group 2 by boiling. The most efficient PCR methods in the Group 1 were those based on kDNA targets. The kDNA PCR-Hybridization was able to detect parasites in 22/23 dogs (95.6%) and in 40/46 samples (86.9%). The kDNA snPCR was positive for 21/23 dogs (91.3%) and for 40/46 samples (86.9%). The positivities of the kDNA based methods were significantly higher than the positivities verified for the methods based on ribosomal rRNA genes (p<0.05). In the Group 2 the kDNA PCR- Hybridization showed a better performance detecting parasites in 18/23 dogs (78.3%) and in 31/46 samples (67.4%), significantly higher than the other three methods (p<0.05). The higher sensitivity of the minicircle kDNA based assays reported by others was confirmed in this study and kDNA PCR-Hybridization showed the best sensitivity among the assays evaluated. (author)

  1. Leishmaniasis visceral en la Argentina: Notificación y situación vectorial (2006-2012

    Ignacio T. Gould

    2013-04-01

    Full Text Available La leishmaniasis visceral (LV en la Argentina se notifica obligatoriamente a través del Sistema Nacional de Vigilancia de la Salud (SNVS. El análisis de la notificación muestra un total de 103 casos distribuidos en cuatro provincias, siendo Misiones la de mayor casuística con un total de 80 casos en 15 localidades, desde mayo 2006 hasta julio de 2012. Los niños de 0 a 15 años de edad son el grupo con mayor incidencia. En el año 2004 fue registrado por primera vez el riesgo de LV urbana endémica en la provincia de Formosa tras el hallazgo del vector Lutzomyia longipalpis. En el año 2006 la provincia de Misiones registra casos de LV humana, LV canina, y la provincia de Corrientes en el verano 2008-2009. En Santiago del Estero los casos de LV humana y LV canina en el año 2008 estuvieron asociados posiblemente a vectores secundarios. En el año 2010 Lu. longipalpis fue hallado en Chajarí, Entre Ríos, mostrando su dispersión hacia el sur. Por ello, para conocer la distribución del riesgo, entre enero y abril del 2011 se realizó búsqueda sistemática del vector de LV en 13 localidades de las provincias de Entre Ríos, Santa Fe y Santiago del Estero, totalizando 275 trampas/noche. Se comprobó la colonización de Lu. longipalpis, en la localidad de Chajarí. En Santiago del Estero no se encontró Lu. longipalpis por lo que Migonemyia migonei sigue incriminada como vector putativo de LV en esta región.

  2. Cutaneous leishmaniasis

    Mehmet Harman

    1990-01-01

    Leishmaniasis is used to describe a spectrum of diseases caused by the parasitic protozoa leishmania spp. and transmitted by infected female sandflies. There are three main forms of the disease; cutaneous, mucocutaneous, and visceral. According to the World Health Organization, almost 12 million people from 98 countries worldwide are currently infected with leishmaniasis, while 350 million people are at risk. It was reported that 2 million new cases are diagnosed every year, with three-fourth...

  3. Spatial distribution of human and canine visceral leishmaniasis in Belo Horizonte, Minas Gerais State, Brasil, 1994-1997 Distribuição espacial da leishmaniose visceral humana e canina em Belo Horizonte, Minas Gerais, Brasil, 1994-1997

    Cláudia Di Lorenzo Oliveira

    2001-10-01

    Full Text Available In this paper, we present spatial analysis of the association between all incidents cases of human Visceral Leishmaniasis and seropositive dogs, from 1994 to 1997 in Belo Horizonte, a large Brazilian city. We geocoded 158 human cases and 11,048 seropositive dogs and compared canine prevalence rates with Human Bayesian Incidence rates in the same areas. We also used Knox's test to evaluate the hypothesis of space-time clustering of human cases in the period. Additionally, we used Kernel's maps for seropositive dogs distribution and located the human cases in the resulting smooth maps. We concluded that human and dog rates are correlated. Also, the Visceral Leishmaniasis in Belo Horizonte spread quickly, but apart from the rates' magnitude, it has kept the same spatial pattern through time. We believe it is possible to use this technique to choose areas to implement control measures against Visceral Leishmaniasis in a more efficient way.Neste artigo, apresentamos uma análise espacial da associação entre todos os casos incidentes de leishmaniose visceral e em cães soropositivos ocorridos em Belo Horizonte no período de 1994 a 1997. Geocodificamos 158 casos humanos e 11.048 cães positivos, comparamos as taxas de prevalência canina por área e as taxas Bayesianas de incidência da doença humana nas mesmas áreas. Usamos o teste de Knox para testar a hipótese de cluster espaço temporal entre os casos humanos no período examinado. Adicionalmente, construímos Mapas de Kernel para cães soropositivos e sobrepusemos os casos humanos em quatro áreas. Os resultados apontam para correlação entre casos humanos e caninos. Além disso, a leishmaniose visceral espalhou-se rapidamente em Belo Horizonte, embora tenha mantido o mesmo padrão durante os anos analisados. Acreditamos ser possível o uso das técnicas empregadas para priorizar áreas onde as medidas de controle devem ser implementadas.

  4. Growth factor and Th2 cytokine signaling pathways converge at STAT6 to promote arginase expression in progressive experimental visceral leishmaniasis.

    E Yaneth Osorio

    2014-06-01

    Full Text Available Host arginase 1 (arg1 expression is a significant contributor to the pathogenesis of progressive visceral leishmaniasis (VL, a neglected tropical disease caused by the intracellular protozoan Leishmania donovani. Previously we found that parasite-induced arg1 expression in macrophages was dependent on STAT6 activation. Arg1 expression was amplified by, but did not require, IL-4, and required de novo synthesis of unknown protein(s. To further explore the mechanisms involved in arg1 regulation in VL, we screened a panel of kinase inhibitors and found that inhibitors of growth factor signaling reduced arg1 expression in splenic macrophages from hamsters with VL. Analysis of growth factors and their signaling pathways revealed that the Fibroblast Growth Factor Receptor 1 (FGFR-1 and Insulin-like Growth Factor 1 Receptor (IGF-1R and a number of downstream signaling proteins were activated in splenic macrophages isolated from hamsters infected with L. donovani. Recombinant FGF-2 and IGF-1 increased the expression of arg1 in L. donovani infected hamster macrophages, and this induction was augmented by IL-4. Inhibition of FGFR-1 and IGF-1R decreased arg1 expression and restricted L. donovani replication in both in vitro and ex vivo models of infection. Inhibition of the downstream signaling molecules JAK and AKT also reduced the expression of arg1 in infected macrophages. STAT6 was activated in infected macrophages exposed to either FGF-2 or IGF-1, and STAT6 was critical to the FGFR-1- and IGF-1R-mediated expression of arg1. The converse was also true as inhibition of FGFR-1 and IGF-1R reduced the activation of STAT6 in infected macrophages. Collectively, these data indicate that the FGFR/IGF-1R and IL-4 signaling pathways converge at STAT6 to promote pathologic arg1 expression and intracellular parasite survival in VL. Targeted interruption of these pathological processes offers an approach to restrain this relentlessly progressive disease.

  5. Successful Therapy of Murine Visceral Leishmaniasis with Astrakurkurone, a Triterpene Isolated from the Mushroom Astraeus hygrometricus, Involves the Induction of Protective Cell-Mediated Immunity and TLR9.

    Mallick, Suvadip; Dutta, Aritri; Chaudhuri, Ankur; Mukherjee, Debasri; Dey, Somaditya; Halder, Subhadra; Ghosh, Joydip; Mukherjee, Debarati; Sultana, Sirin Salma; Biswas, Gunjan; Lai, Tapan Kumar; Patra, Pradyumna; Sarkar, Indranil; Chakraborty, Sibani; Saha, Bhaskar; Acharya, Krishnendu; Pal, Chiranjib

    2016-05-01

    In our previous report, we showed that astrakurkurone, a triterpene isolated from the Indian mushroom Astraeus hygrometricus (Pers.) Morgan, induced reactive oxygen species, leading to apoptosis in Leishmania donovani promastigotes, and also was effective in inhibiting intracellular amastigotes at the 50% inhibitory concentration of 2.5 μg/ml. The aim of the present study is to characterize the associated immunomodulatory potentials and cellular activation provided by astrakurkurone, leading to effective antileishmanial activity in vitro and in vivo Astrakurkurone-mediated antileishmanial activity was evaluated by real-time PCR and flow cytometry. The involvement of Toll-like receptor 9 (TLR9) was studied by in vitro assay in the presence of a TLR9 agonist and antagonist and by in silico modeling of a three-dimensional structure of the ectodomain of TLR9 and its interaction with astrakurkurone. Astrakurkurone caused a significant increase in TLR9 expression of L. donovani-infected macrophages along with the activation of proinflammatory responses. The involvement of TLR9 in astrakurkurone-mediated amastigote killing has been evidenced from the fact that a TLR9 agonist (CpG, ODN 1826) in combination with astrakurkurone enhanced the amastigote killing, while a TLR9 antagonist (bafilomycin A1) alone or in combination with astrakurkurone curbed the amastigote killing, which could be further justified by in silico evidence of docking between mouse TLR9 and astrakurkurone. Astrakurkurone was found to reduce the parasite burden in vivo by inducing protective cytokines, gamma interferon and interleukin 17. Moreover, astrakurkurone was nontoxic toward peripheral blood mononuclear cells of immunocompromised patients with visceral leishmaniasis. Astrakurkurone, a nontoxic antileishmanial, enhances the immune efficiency of host cells, leading to parasite clearance in vitro and in vivo. PMID:26883702

  6. Xenodiagnosis on dogs with visceral leishmaniasis: Canine and sand fly aspects related to the parasite transmission.

    Magalhães-Junior, Jairo Torres; Mota, Tiago Feitosa; Porfirio-Passos, Gabriela; Larangeira, Daniela Farias; Franke, Carlos Roberto; Barrouin-Melo, Stella Maria

    2016-06-15

    One of the main limitations for the effective control of canine leishmaniasis in endemic areas is the difficulty in identifying infectious dogs. The objective of this study was to determine factors, related to dogs and to parasite detection in sand flies, which are associated with the positive xenodiagnosis of Leishmania infantum using the vector Lutzomyia longipalpis. The xenodiagnosis was performed in 50 owned dogs residing in endemic areas, which were divided into three different groups: G1-26 dogs proved to be infected and classified by severity of VL clinical signs on physical examination; G2-15 dogs proved to be infected and classified by severity of clinical signs and intensity of laboratory abnormalities; G3-nine dogs that were seropositive for anti-Leishmania IgG in ELISA tests. Parasite search in the sand flies after having fed on dogs in the xenodiagnosis was performed by both methodologies, PCR and dissection followed by microscopy. In G1, 58% (15/26) of dogs were able to transmit Leishmania to the vector, when parasite detection in sand flies were performed by PCR technique, 5 days after blood meal, whereas in G2, 53% (8/15) transmitted the parasite to the vector, however, confirmation was performed by direct observation of parasite through optical miscroscopy held 10 days after blood meal. Rate of infectiousness of dogs to sand flies was positively associated to severity of disease (p=0.042 and p=0.040), regardless the method used for clinical classification or for parasite detection in sand flies after xenodiagnosis. In G1 30% (3/10) of dogs with subclinical infection were infectious to the vector, while 80% (12/16) of dogs with clinical disease were also infectious. Even more, 17% (1/6) of dogs that had moderate disease were infectious to the sand flies, while 78% (7/9) of dogs with severe disease were infectious in G2. Still in G2, the proportion of sand flies infected (grade of infectiousness) was significantly lower (p=0.0098) when they fed on

  7. A Current Perspective on Leishmaniasis

    Angela Clem

    2010-01-01

    There are many challenges facing the successful control and eradication of cutaneous and visceral leishmaniasis. Leishmaniasis is still endemic in many poverty stricken and war torn areas. Through the use of an extensive literature review, this article examined the global disease burden of cutaneous and visceral leishmaniasis. Surveillance and control measures for leishmaniasis being used by the World Health Organization were also discussed in this article. Finally, potential new treatments a...

  8. Leishmaniasis vector behaviour in Kenya

    Leishmaniasis in Kenya exists in two forms: cutaneous and visceral. The vectors of visceral leishmaniasis have been the subject of investigation by various researchers since World War II, when the outbreak of the disease was first noticed. The vectors of cutaneous leishmaniasis were first worked on only a decade ago after the discovery of the disease focus in Mt. Elgon. The vector behaviour of these diseases, namely Phlebotomus pedifer, the vector of cutaneous leishmaniasis, and Phlebotomus martini, the vector of visceral leishmaniasis, are discussed in detail. P. pedifer has been found to breed and bite inside caves, whereas P. martini mainly bites inside houses. (author)

  9. Coinfection of Leishmania chagasi with Toxoplasma gondii, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) in cats from an endemic area of zoonotic visceral leishmaniasis.

    Sobrinho, Ludmila Silva Vicente; Rossi, Cláudio Nazaretian; Vides, Juliana Peloi; Braga, Eveline Tozzi; Gomes, Ana Amélia Domingues; de Lima, Valéria Marçal Félix; Perri, Sílvia Helena Venturoli; Generoso, Diego; Langoni, Hélio; Leutenegger, Christian; Biondo, Alexander Welker; Laurenti, Márcia Dalastra; Marcondes, Mary

    2012-06-01

    The aim of the present study was to determine the coinfection of Leishmania sp. with Toxoplasma gondii, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) in a population of cats from an endemic area for zoonotic visceral leishmaniasis. An overall 66/302 (21.85%) cats were found positive for Leishmania sp., with infection determined by direct parasitological examination in 30/302 (9.93%), by serology in 46/302 (15.23%) and by both in 10/302 (3.31%) cats. Real time PCR followed by amplicon sequencing successfully confirmed Leishmania infantum (syn Leishmania chagasi) infection. Out of the Leishmania infected cats, coinfection with FIV was observed in 12/66 (18.18%), with T. gondii in 17/66 (25.75%) and with both agents in 5/66 (7.58%) cats. FeLV was found only in a single adult cat with no Leishmania infection. A positive association was observed in coinfection of Leishmania and FIV (p0.05). In conclusion, cats living in endemic areas of visceral leishmaniasis are significantly more likely to be coinfected with FIV, which may present confounding clinical signs and therefore cats in such areas should be always carefully screened for coinfections. PMID:22285010

  10. Research progress on the diagnostic methods of visceral leishmaniasis%内脏利什曼病诊断方法研究进展

    汪俊云; 高春花

    2009-01-01

    Visceral leishmaniasis is an important parasitosis which severely damages the health of people in the world.Rapid and accurate diagnosis is crucial in treatment and control of the disease.In this paper we reviewed the progress on the diagnostic methods of visceral leishmaniasis.%内脏利什曼病(黑热病)是在世界范围内流行的严重危害人类健康的重要寄生虫病.发展快速而又准确的诊断技术是治疗和控制该病的关键之一.随着免疫学技术、分子生物学技术的应用,黑热病的诊断技术不断取得进展,相应地我国黑热病诊断技术的研究和应用也在不断进步.该文就黑热病诊断技术研究取得的进展作一综述.

  11. Introducing Single Dose Liposomal Amphotericin B for the Treatment of Visceral Leishmaniasis in Rural Bangladesh: Feasibility and Acceptance to Patients and Health Staff

    Eva-Maria Maintz

    2014-01-01

    Full Text Available Background. For the treatment of visceral leishmaniasis in Bangladesh, single dose liposomal amphotericin B (ambisome is supposed to be the safest and most effective treatment. Specific needs for application and storage raise questions about feasibility of its implementation and acceptance by patients and health staff. Methods. The study was carried out in the most endemic district of Bangladesh. Study population includes patients treated with ambisome or miltefosine, hospital staff, and a director of the national visceral leishmaniasis program. Study methods include direct observation (subdistrict hospitals, open interviews (heath staff and program personnel, structured questionnaires, and focus group discussions (patients. Results. Politicalcommitment for ambisome is strong; the general hospital infrastructure favours implementation but further strengthening is required, particularly for drug storage below 25°C (refrigerators, back-up energy (fuel for generators, and supplies for ambisome administration (like 5% dextrose solution. Ambisome created high satisfaction in patients and hospital staff, less adverse events, and less income loss for patients compared to miltefosine. Conclusions. High political commitment, general capacities of subdistrict hospitals, and high acceptability favour the implementation of ambisome treatment in Bangladesh. However, strengthening of the infrastructure and uninterrupted supplies of essential accessories is mandatory before introducing sLAB in Bangladesh.

  12. The involvement of TLR2 and TLR4 in cytokine and nitric oxide production in visceral leishmaniasis patients before and after treatment with anti-leishmanial drugs.

    Mariana Gatto

    Full Text Available Toll-like receptors (TLRs have significant involvement in Leishmania infection, although little is known about the relationship between these receptors, cytokines and nitric oxide (NO in patients with visceral leishmaniasis (VL before or after treatment with anti-leishmanial drugs. The goal of this study was to evaluate the expression of TLR2 and TLR4 in CD3+ and CD14+ cells and the production of TNF-α, IFN-γ, IL-17, IL-10, TGF-β and NO in peripheral blood mononuclear cells (PBMCs from VL patients pre- and post-treatment with anti-leishmanial drugs. In addition, we investigated whether these receptors were involved in the production of these cytokines and NO. In the active VL patients, increased TLR2 and TLR4 expression in lymphocytes and monocytes, increased production of TNF-α, IL-10 and TGF-β and decreased production of IFN-γ, IL-17 and NO were observed. After treatment, TLR2 and TLR4 were still expressed in lymphocytes and monocytes, the TNF-α and IL-10 levels were lower, the production of IFN-γ, IL-17 and NO was higher, and the TGF-β level remained high. Before treatment, the production of TNF-α and NO was associated with TLR2 and TLR4 expression, while IL-10 production was only associated with TLR2 expression. After treatment, both receptors were associated with the production of TNF-α, IFN-γ, IL-10 and NO, while the production of IL-17 was associated only with TLR4 expression. The results presented in this study suggest that both TLR2 and TLR4 participate in the modulation of cytokine and NO production in VL patients, contributing to the pathogenesis of VL prior to treatment and the protective immune response after treatment.

  13. Validity and reliability of enzyme immunoassays using Leishmania major or L. infantum antigens for the diagnosis of canine visceral leishmaniasis in Brazil.

    Mauro Maciel de Arruda

    Full Text Available BACKGROUND: American visceral leishmaniasis is caused by the protozoan Leishmania infantum. Dogs are the main reservoirs in the domestic transmission cycle. The limited accuracy of diagnostic tests for canine leishmaniasis may contribute to the lack of impact of control measures recommended by the Brazilian Ministry of Health. The objective of this study was to estimate the accuracy of two enzyme-linked immunosorbent assays employing L. major or L. infantum antigens and their reliability between three laboratories of different levels of complexity. METHODS: A validation study of ELISA techniques using L. major or L. infantum antigens was conducted. Direct visualization of the parasite in hematoxylin/eosin-stained histopathological sections, immunohistochemistry, and isolation of the parasite in culture.were used as gold standard. An animal that was positive in at least one of the tests was defined as infected with L. infantum. Serum samples collected from 1,425 dogs were analyzed. Samples were separated in three aliquots and tested in three different laboratories. Sensitivity, specificity and the area under de ROC curve were calculated and the reliability was evaluated between the participant laboratories. RESULTS: The sensitivity was 91.8% and 89.8% for the L. major and L. infantum assays, respectively. The specificity was 83.75% and 82.7% for the L. major and L. infantum assays, respectively. The area under de ROC curve was 0.920 and 0.898 for L. major and L. infantum, respectively. The mean intraclass correlation coefficients between laboratories ranged from 0.890 to 0.948 when L. major was used as antigen, and from 0.818 to 0.879 when L. infantum was used. INTERPRETATION: ELISA tests using L. major or L. infantum antigens have similar accuracy and reliability. Our results do not support the substitution of the L. major antigen of the ELISA test currently used for the diagnosis of canine visceral leishmaniasis in Brazil.

  14. A new Leishmania-specific hypothetical protein and its non-described specific B cell conformational epitope applied in the serodiagnosis of canine visceral leishmaniasis.

    Lage, Daniela P; Martins, Vívian T; Duarte, Mariana C; Costa, Lourena E; Garde, Esther; Dimer, Laura M; Kursancew, Amanda C S; Chávez-Fumagalli, Miguel A; de Magalhães-Soares, Danielle F; Menezes-Souza, Daniel; Roatt, Bruno M; Machado-de-Ávila, Ricardo A; Soto, Manuel; Tavares, Carlos A P; Coelho, Eduardo A F

    2016-04-01

    The serodiagnosis of canine visceral leishmaniasis (CVL) presents problems related to its sensitivity and/or specificity. In the present study, a new Leishmania-specific hypothetical protein, LiHyD, was produced as a recombinant protein (rLiHyD) and evaluated in ELISA experiments for the CVL serodiagnosis. LiHyD was characterized as antigenic in a recent immunoproteomic search performed with Leishmania infantum proteins and the sera of dogs developing visceral leishmaniasis (VL). Aiming to compare the efficacy between whole proteins and synthetic peptides, two linear and one conformational B cell epitopes of LiHyD were synthesized and also evaluated as diagnostic markers. The four antigens were recognized by the sera of dogs suffering VL. On the contrary, low reactivity was observed when they were assayed with sera from non-infected healthy dogs living in endemic or non-endemic areas of leishmaniasis. In addition, no reactivity was found against them using sera from dogs experimentally infected by Trypanosoma cruzi, Babesia canis, or Ehrlichia canis, or sera from animals vaccinated with the Leish-Tec® vaccine, a prophylactic preparation commercially available for CVL prevention in Brazil. As comparative diagnostic tools, a recombinant version of the amastigote-specific A2 protein and a soluble crude Leishmania extract were studied. Both antigens presented lower sensitivity and/or specificity values than the LiHyD-based products. The rLiHyD presented better results for the CVL serodiagnosis than its linear epitopes, although the peptide recreating the conformational epitope resulted also appropriate as a diagnostic marker of CVL. To the best of our knowledge, this is the first study showing the use of a conformational epitope derived from a Leishmania protein for serodiagnosis of CVL. PMID:26782811

  15. Age-related alteration of arginase activity impacts on severity of leishmaniasis.

    Ingrid Müller

    Full Text Available BACKGROUND: The leishmaniases are a group of vector-borne parasitic diseases that represent a major international public health problem; they belong to the most neglected tropical diseases and have one of the highest rates of morbidity and mortality. The clinical outcome of infection with Leishmania parasites depends on a variety of factors such as parasite species, vector-derived products, genetics, behaviour, and nutrition. The age of the infected individuals also appears to be critical, as a significant proportion of clinical cases occur in children; this age-related higher prevalence of disease is most remarkable in visceral leishmaniasis. The mechanisms resulting in this higher incidence of clinical disease in children are poorly understood. We have recently revealed that sustained arginase activity promotes uncontrolled parasite growth and pathology in vivo. Here, we tested the hypothesis that arginase-mediated L-arginine metabolism differs with age. METHODOLOGY: The age distribution of patients with visceral or cutaneous leishmaniasis was determined in cohorts of patients in our clinics in endemic areas in Ethiopia. To exclude factors that are difficult to control in patients, we assessed the impact of ageing on the manifestations of experimental leishmaniasis. We determined parasite burden, T cell responses, and macrophage effector functions in young and aged mice during the course of infection. RESULTS: Our results show that younger mice develop exacerbated lesion pathology and higher parasite burdens than aged mice. This aggravated disease development in younger individuals does not correlate with a change in T helper cytokine profile. To address the underlying mechanisms responsible for the more severe infections in younger mice, we investigated macrophage effector functions. Our results show that macrophages from younger mice do not have an impaired capacity to kill parasites; however, they express significantly higher levels of

  16. Visceral Leishmaniasis in Southwestern Iran: A Retrospective Clinico-Hematological Analysis of 380 Consecutive Hospitalized Cases (1999–2014)

    Sarkari, Bahador; Naraki, Tahereh; Ghatee, Mohammad Amin; Abdolahi Khabisi, Samaneh; Davami, Mohammad Hassan

    2016-01-01

    Visceral Leishmaniasis (VL) is an endemic parasitic disease and remains as a major health concern in southwestern Iran. The current study describes clinico-hematological, epidemiological and therapeutic features of VL cases, admitted to university-affiliated hospitals, during 1999–2014 in Fars province, southwestern Iran. A total of 380 VL cases were recorded during a 16 years period, giving an average annual admission of 23.75 cases/year in which 217 (57.1%) were male and 163 (42.9%) were female. Mean age of the patients was 3.7 years. The majority of the cases (91.5%) were ≤ 5 years old. Bone-marrow aspiration detected Leishmania amastigotes only in 26.6% of cases. Fever (98.1%), abdominal protrusion (65.1%) and hepatosplenomegaly (63.7%) were the most common clinical presentations of the patients. Pancytopenia was noted in 43.1, anemia in 87.3 and thrombocytopenia in 64% of cases. Increase in the level of AST (aspartate aminotransferase), ALT (alanine aminotransferase), alkaline phosphatase, LDH (lactate dehydrogenase) and CRP (C-Reactive Proteins) were seen in 84.9, 53.6, 44.4, 72.5 and 83.1% of cases, respectively. Mortality was noted in 5.3% of cases. Deranged haemato-biochemical parameters including total and direct bilirubin, PLT (platelet) and pancytopenia were significantly contributed to mortality from VL. Moreover, clinical features such as severe splenomegaly as well as bacterial infections were meaningfully contributed to death from VL. The majority of patients (74.9%) were treated with meglumine antimoniate. Amphotericin B was administrated in 59 of cases, 11 of them were initially treated with meglumine antimoniate with a shift to amphotericin B, because of treatment failure. Findings of the current study demonstrated that VL is present in southwest of Iran with a fairly continual rate during the last 16 years period. Deranged haemato-biochemical parameters along with severe splenomegaly contributed to mortality from VL. PMID:26942443

  17. Visceral Leishmaniasis in Southwestern Iran: A Retrospective Clinico-Hematological Analysis of 380 Consecutive Hospitalized Cases (1999-2014).

    Sarkari, Bahador; Naraki, Tahereh; Ghatee, Mohammad Amin; Abdolahi Khabisi, Samaneh; Davami, Mohammad Hassan

    2016-01-01

    Visceral Leishmaniasis (VL) is an endemic parasitic disease and remains as a major health concern in southwestern Iran. The current study describes clinico-hematological, epidemiological and therapeutic features of VL cases, admitted to university-affiliated hospitals, during 1999-2014 in Fars province, southwestern Iran. A total of 380 VL cases were recorded during a 16 years period, giving an average annual admission of 23.75 cases/year in which 217 (57.1%) were male and 163 (42.9%) were female. Mean age of the patients was 3.7 years. The majority of the cases (91.5%) were ≤ 5 years old. Bone-marrow aspiration detected Leishmania amastigotes only in 26.6% of cases. Fever (98.1%), abdominal protrusion (65.1%) and hepatosplenomegaly (63.7%) were the most common clinical presentations of the patients. Pancytopenia was noted in 43.1, anemia in 87.3 and thrombocytopenia in 64% of cases. Increase in the level of AST (aspartate aminotransferase), ALT (alanine aminotransferase), alkaline phosphatase, LDH (lactate dehydrogenase) and CRP (C-Reactive Proteins) were seen in 84.9, 53.6, 44.4, 72.5 and 83.1% of cases, respectively. Mortality was noted in 5.3% of cases. Deranged haemato-biochemical parameters including total and direct bilirubin, PLT (platelet) and pancytopenia were significantly contributed to mortality from VL. Moreover, clinical features such as severe splenomegaly as well as bacterial infections were meaningfully contributed to death from VL. The majority of patients (74.9%) were treated with meglumine antimoniate. Amphotericin B was administrated in 59 of cases, 11 of them were initially treated with meglumine antimoniate with a shift to amphotericin B, because of treatment failure. Findings of the current study demonstrated that VL is present in southwest of Iran with a fairly continual rate during the last 16 years period. Deranged haemato-biochemical parameters along with severe splenomegaly contributed to mortality from VL. PMID:26942443

  18. Comparison of visceral leishmaniasis diagnostic antigens in African and Asian Leishmania donovani reveals extensive diversity and region-specific polymorphisms.

    Tapan Bhattacharyya

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL, caused by infection with Leishmania donovani complex, remains a major public health problem in endemic regions of South Asia, East Africa, and Brazil. If untreated, symptomatic VL is usually fatal. Rapid field diagnosis relies principally on demonstration of anti-Leishmania antibodies in clinically suspect cases. The rK39 immunochromatographic rapid diagnostic test (RDT is based on rK39, encoded by a fragment of a kinesin-related gene derived from a Brazilian L. chagasi, now recognised as L. infantum, originating from Europe. Despite its reliability in South Asia, the rK39 test is reported to have lower sensitivity in East Africa. A reason for this differential response may reside in the molecular diversity of the rK39 homologous sequences among East African L. donovani strains. METHODOLOGY/PRINCIPAL FINDINGS: Coding sequences of rK39 homologues from East African L. donovani strains were amplified from genomic DNA, analysed for diversity from the rK39 sequence, and compared to South Asian sequences. East African sequences were revealed to display significant diversity from rK39. Most coding changes in the 5' half of repeats were non-conservative, with multiple substitutions involving charge changes, whereas amino acid substitutions in the 3' half of repeats were conservative. Specific polymorphisms were found between South Asian and East African strains. Diversity of HASPB1 and HASPB2 gene repeat sequences, used to flank sequences of a kinesin homologue in the synthetic antigen rK28 designed to reduce variable RDT performance, was also investigated. Non-canonical combination repeat arrangements were revealed for HASPB1 and HASPB2 gene products in strains producing unpredicted size amplicons. CONCLUSIONS/SIGNIFICANCE: We demonstrate that there is extensive kinesin genetic diversity among strains in East Africa and between East Africa and South Asia, with ample scope for influencing performance of rK39

  19. Visceral leishmaniasis relapse in Southern Sudan (1999-2007: a retrospective study of risk factors and trends.

    Stanislaw Gorski

    Full Text Available BACKGROUND: Risk factors associated with L. donovani visceral leishmaniasis (VL; kala azar relapse are poorly characterized. METHODS: We investigated patient characteristics and drug regimens associated with VL relapse using data from Médecins Sans Frontières - Holland (MSF treatment centres in Southern Sudan. We used MSF operational data to investigate trends in VL relapse and associated risk factors. RESULTS: We obtained data for 8,800 primary VL and 621 relapse VL patients treated between 1999 and 2007. Records of previous treatment for 166 VL relapse patients (26.7% were compared with 7,924 primary VL patients who had no record of subsequent relapse. Primary VL patients who relapsed had larger spleens on admission (Hackett grade >or=3 vs 0, odds ratio (OR for relapse = 3.62 (95% CI 1.08, 12.12 and on discharge (Hackett grade >or=3 vs 0, OR = 5.50 (1.84, 16.49. Age, sex, malnutrition, mobility, and complications of treatment were not associated with risk of relapse, nor was there any trend over time. Treatment with 17-day sodium stibogluconate/paromomycin (SSG/PM combination therapy vs 30-day SSG monotherapy was associated with increased risk of relapse (OR = 2.08 (1.21, 3.58 but reduced risk of death (OR = 0.27 (0.20, 0.37, although these estimates are likely to be residually confounded. MSF operational data showed a crude upward trend in the proportion of VL relapse patients (annual percentage change (APC = 11.4% (-3.4%, 28.5% and a downward trend in deaths (APC = -18.1% (-22.5%, -13.4%. CONCLUSIONS: Splenomegaly and 17-day SSG/PM vs 30-day SSG were associated with increased risk of VL relapse. The crude upward trend in VL relapses in Southern Sudan may be attributable to improved access to treatment and reduced mortality due to SSG/PM combination therapy.

  20. Antileishmanial potential of a marine spongeHaliclona oculataagainst experimental visceral leishmaniasis

    Vijai Lakshmi; Prashant Khare; Pragya Misra; Mahendra Nath Srivastava; Anuradha Dube

    2015-01-01

    Objective:To evaluate the antileishmanial activity of a marine spongeHaliclona oculata. Methods:The crude methanol extract was prepared from the freshly collected sponge and its three fractions were also prepared by maceration method. The antileishmanial activity of these extract and fractions was tested againstLeishmania donovani. Results:The antileishmanial activity was tested bothin vitroand in vivo. The crude methanol extract exerted almost complete inhibition of promastigotes (81.0%±6.9%) and 78.8%±5.2% inhibition of intracellular amastigotes at 100 μg/mL with IC50 values of 29.5 μg/mL and 40.6 μg/mL, respectively. The treatment of 500 mg/kg(p.o.) of the crude methanol extract for 5 d for Leishmania donovani infected hamsters resulted in 78.35%±10.20% inhibition of intracellular amastigotes. At a lower dose (250 mg/kg), it exhibited poor efficacy. Among the fractions, highestin vitro(>75%) and in vivo (84.3%±10.2%) antileishmanial activity was observed in n-chloroform fraction with IC50 values of 54.2 μg/mL and 61 μg/mL against promastigotes and intracellular amastigotes, respectively. Hexane fraction andn-butanol (both insoluble and soluble) fractions were found inactivein vitroand in vivo. Conclusions:Our findings indicate that this marine sponge has the potential to provide new insight toward development of an effective antileishmanial agent and, hence, more exhaustive studies are needed for exploiting the vast marine resources of the world to combat the scourge of several parasitic diseases.

  1. Is severe visceral leishmaniasis a systemic inflammatory response syndrome? A case control study A leishmaniose visceral grave é uma síndrome da resposta inflamatória sistêmica? Um estudo caso-controle

    Carlos Henrique Nery Costa

    2010-08-01

    Full Text Available INTRODUCTION: The objective of the study is to identify the main risk factors for death by New World visceral leishmaniasis and establish a coherent pathogenic substrate of severe disease based on clinical findings. METHODS: Seventy-six deceased inpatients and 320 successfully treated inpatients with VL were studied in a case control study. RESULTS: Bacterial infection and bleeding were mutually exclusive events leading to death. Five risk factors were unique for death by bacterial infection (malnutrition, pulmonary rales, severe anemia, severe absolute neutropenia and higher neutrophil count, while another six were unique for death by bleeding (jaundice, severe relative neutropenia, severe thrombocytopenia, liver injury, kidney failure, higher bone marrow parasite load. Bacterial infection, bleeding, severe anemia, diarrhea, dyspnea, edema, jaundice and bone marrow parasite load were the main syndromes of visceral leishmaniasis among successfully treated patients. CONCLUSIONS: The data support the idea that bacterial infections are due to immune paralysis. Broad organ and system involvement is plausibly due to the high production of proinflammatory cytokines, whose actions fit well with visceral leishmaniasis. The syndromes and causative mediators are typical of a slowly developing systemic inflammatory response syndrome.INTRODUÇÃO: O objetivo do estudo foi i dentificar os principais fatores de risco para morte na leishmaniose visceral do Novo Mundo e estabelecer um substrato patogênico baseado nos achados clínicos coerente para doença grave. MÉTODOS: Em um estudo caso-controle, foram estudados 76 pacientes internados que faleceram e 320 pacientes internados tratados com sucesso. RESULTADOS: Infecção bacteriana e sangramento foram eventos que levaram à morte, mutuamente exclusivos. Cinco fatores de risco foram únicos para morte por infecção bacteriana (desnutrição, estertores pulmonares, anemia grave, neutropenia absoluta grave e

  2. Evaluation of antibody responses in american visceral leishmaniasis by ELISA and immunoblot Avaliação da resposta imune humoral na leishmaniose visceral americana pelos métodos ELISA e "immunoblot"

    Thomas G. Evans

    1989-06-01

    Full Text Available American visceral leishmaniasis (AVL is an important disease among children of northeast Brazil. In order to characterize antibody responses during AVL, sera of hospitalized patients were analyzed by ELISA and Western blot using a Leishmania chagasi antigen preparation. The ELISA was positive (asorbance [greater than or equals to] 0.196 at a serum dilution of 1:1024 in all patients at presentation, and fell to ward control levels over the following year. Only one of 72 control subjects tested positive, and that donor had a sibling with AVL. Immunoblots of the patients' sera recognized multiple bands, the most frequent of which were at approximately 116 kDa, 70 kDa, and 26 kDa. Less frenquently observed were bands at approximately 93 kDa, 74 kDa, 62 kDa, 46 kDa and 32 kDa. The ELISA responses and patterns of banding were distinctive for AVL, and could be used to differentiate patients with AVL from those with Chagas' disease of cutaneous leishmaniasis. Sera from six AVL patients followed for up to six weeks after treatment identified no new bands. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE of surface iodinated parasite proteins showed one major band and four minor bands, whereas SDS-PAGE of biotinylated prarasite proteins revealed a banding pattern similar to those of patient sera. AVL appears to produce characteristic immunoblot patterns which can be used along with a sensitive screening ELISA to diagnose AVL.A leishmaniose visceral americana é uma doença importante entre crianças do nordeste do Brasil. Com o objetivo de caracterizar a resposta imune humoral durante o curso da doença, foram analisados soros de pacientes hospitalizados, pelos métodos ELISA e Western blot, usando-se preparaçöes de antígenos de Leishmania donovani chagasi. O teste de ELISA foi positivo (absorbância > 0,196, numa diluiçäo de 1: 1024, em todos os pacientes no início da doença, diminuindo no decorrer do ano, para os níveis dos

  3. Travelers' Health: Leishmaniasis, Visceral

    ... Learn About Destination See a Doctor Pre-Travel Appointment Your Health Status How Diseases Spread Pack Smart ... such as in northeastern Brazil). In the Old World (Eastern Hemisphere), VL is found in parts of ...

  4. Who Is a Typical Patient with Visceral Leishmaniasis? Characterizing the Demographic and Nutritional Profile of Patients in Brazil, East Africa, and South Asia

    Harhay, Michael O.; Olliaro, Piero L.; Vaillant, Michel; Chappuis, François; Lima, María Angeles; Ritmeijer, Koert; Costa, Carlos Henrique; Costa, Dorcas Lamounier; Rijal, Suman; Sundar, Shyam; Balasegaram, Manica

    2011-01-01

    Drug-dosing recommendations for visceral leishmaniasis (VL) treatment are based on the patients' weight or age. A current lack of demographic and anthropometric data on patients hinders (1) the ability of health providers to properly prepare for patient management, (2) an informed drug procurement for disease control, and (3) the design of clinical trials and development of new drug therapies in the different endemic areas. We present information about the age, gender, weight, and height of 29,570 consecutive VL patients presenting to 20 locations in six geographic endemic regions of Brazil, East Africa, Nepal, and India between 1997 and 2009. Our compilation shows substantial heterogeneity in the types of patients seeking care for VL at the clinics within the different locations. This suggests that drug development, procurement, and perhaps even treatment protocols, such as the use of the potentially teratogenic drug miltefosine, may require distinct strategies in these geographic settings. PMID:21460007

  5. Studies on the Feeding Habits of Lutzomyia (Lutzomyia longipalpis (Lutz & Neiva, 1912 (Diptera: Psychodidae: Phlebotominae Populations from Endemic Areas of American Visceral Leishmaniasis in Northeastern Brazil

    Margarete Martins dos Santos Afonso

    2012-01-01

    Full Text Available The aim of this study was to identify potential blood feeding sources of L. (L. longipalpis specimens from populations in Northeastern Brazil, endemic areas of American Visceral Leishmaniasis (AVL and its correlation with the transmission of L. (L. i. chagasi. The ELISA technique was applied using bird, dog, goat, opossum, equine, feline, human, sheep, and rodent antisera to analyze 609 females, resulting in an overall positivity of 60%. In all municipalities, females showed higher positivity for bird followed by dog antiserum and sand fly specimens were also positive for equine, feline, human, sheep, goat, opossum, and rodent antisera. The finding for 17 combinations of two or three types of blood in some females corroborates the opportunistic habit of this sand fly species. The results demonstrating the association between L. (L. longipalpis and opossum suggest the need for further evaluation of the real role of this synanthropic mammal in the eco-epidemiology of AVL.

  6. Cutaneous and visceral leishmaniasis co-infection in dogs from Rio de Janeiro, Brazil: evaluation by specific PCR and RFLP-PCR assays

    Marize Quinhones Pires

    2014-04-01

    Full Text Available Introduction During a diagnostic evaluation of canine visceral leishmaniasis (VL, two of seventeen dogs were found to be co-infected by Leishmania (Viannia braziliensis and Leishmania (Leishmania chagasi. Methods Specific polymerase chain reaction (PCR and restriction fragment length polymorphism-PCR (RFLP-PCR assays were performed. Results PCR assays for Leishmania subgenus identification followed by RFLP-PCR analysis in biopsies from cutaneous lesions and the spleen confirmed the presence of Leishmania (Viannia braziliensis and Leishmania (Leishmania chagasi in those fragments. Conclusions This report reinforces the importance of using serological and molecular techniques in the epidemiological surveillance of canine populations in endemic areas in which both diseases are known to co-exist. In such cases, a reassessment of the control measures is required.

  7. Protective vaccination against experimental canine visceral leishmaniasis using a combination of DNA and protein immunization with cysteine proteinases type I and II of L. infantum.

    Rafati, Sima; Nakhaee, Alireza; Taheri, Tahere; Taslimi, Yasaman; Darabi, Haideh; Eravani, Davood; Sanos, Stephanie; Kaye, Paul; Taghikhani, Mohammad; Jamshidi, Shahram; Rad, Mohammad Ali

    2005-05-25

    Leishmania infantum is known to be associated with visceral leishmaniasis in Iran and canids are natural reservoirs. Control of disease in dogs appears to be one of the most effective approaches for interrupting the domestic cycle of the disease. In search for successful vaccine strategies, we evaluated the cysteine proteinases (CPs) type I and II using a heterologous prime-boost regime for vaccination against experimental visceral leishmaniasis in dogs. Following vaccination and challenge, dogs were followed for 12 months. Ten dogs vaccinated by prime/boost with DNA/recombinant CPs (in combination with CpG ODN and Montanide 720) remained free of infection in their bone morrow. In contrast, three out of four dogs in the control groups had infection in their bone marrow. The peripheral lymphocytes from protected animals had generally higher proliferation responses to F/T antigen, recombinant CPA (rCPA) and recombinant CPB (rCPB) than controls. During post-challenge period, the difference in stimulation index is significant (pdogs had elevated IFN-gamma mRNA in peripheral blood mononuclear cells (PBMC), whereas there was a consistent increase in the level of IL-10 in the control groups and some vaccinated dogs. The level of total IgG and IgG2, but not IgG1, to rCPA and rCPB was significantly higher in the vaccinated group (pdog, all dogs in the vaccinated group in comparison to control dogs had strong DTH responses. We propose that the combination of DNA and recombinant protein vaccination using CPs could be instrumental to control (VL) in dogs. PMID:15882533

  8. Immunogenicity and efficacy of recombinant 78 kDa antigen of Leishmania donovani formulated in various adjuvants against murine visceral leishmaniasis

    Rajeev; Nagill; Tejinder; Kaur; Jyoti; Joshi; Sukhbir; Kaur

    2015-01-01

    Objective: To analyze the protective efficacy of recombinant 78 kDa antigen of Leishmania donovani in combination with two adjuvants, that is, cationic liposomes or MPL-A against visceral leishmaniasis in BALB/c mice. Methods: The genomic DNA of promastigotes was isolated and 583 bp of T cell epitopes of gene encoding 78 k Da was amplified using specific primers. The amplified gene was cloned into p ET28 c, transformed into Escherichia coli BL21(DE3) and got expressed after IPTG induction. The recombinant protein was then purified using Ni-NTA and named r78. Three groups of mice were immunized with 10 μg of r78 plus MPL-A, r78 encapsulated in positively charged liposomes and control animals immunized with PBS. Two booster doses were given with the respective vaccine at an interval of 2 weeks each. Mice were challenged with 1×107 Leishmania promastigotes and sacrificed on different post infection/challenge days. Results: Immunization with r78 along with MPL-A and liposomeencapsulated r78 brought a significant reduction in parasite load. In comparison to the infected controls, the parasite load declined by 96.2% in mice immunized with r78 plus MPL-A and 97.23% in animals immunized with liposome-encapsulated r78. The immunized animals also exhibited profound DTH response. The serum antibody responses increased from 15 to 90 days post infection/challenge. Immunized animals showed greater IgG2 a levels and lesser Ig G1 levels in comparison to the infected controls. The splenocytes from immunized mice were cultured, stimulated with r78 and analyzed for cytokine profile. The levels of IL-2 and IFN-γ were greater in immunized animals as compared to control mice. Conclusions: The study proves that r78 in combination with suitable adjuvants is a potential vaccine candidate and may be instrumental in control of visceral leishmaniasis.

  9. Application of Flumethrin Pour-On on Reservoir Dogs and Its Efficacy against Sand Flies in Endemic Focus of Visceral Leishmaniasis, Meshkinshahr, Iran

    MohammadReza Jalilnavaz

    2015-10-01

    Full Text Available Background: Visceral leishmaniasis (VL is one of the most important parasitic zoonotic diseases in the world. Do­mestic dogs are the main domestic reservoirs of VL in endemic foci of Iran. Various methods, including vaccination, treatment of dogs, detection and removal of infected dogs have different results around the world. General policy on control of canine visceral leishmaniasis is protection of them from sand fly bites. The aim of this study was evalua­tion of pour-on application of flumethrin on dogs against blood-feeding and mortality of field-caught sand flies.Methods: Once every 20 days from May untill September 2013, the treated and control dogs were exposed with field caught sandflies for 2 hours under bed net traps. After the exposure time, both alive and dead sand flies were trans­ferred in netted cups to the laboratory. The mortality rate of them was assessed after 24 hours. The blood-fed or un­fed conditions were determined 2 hours after exposure to the dogs under stereomicroscope.Results: The blood feeding index was varied from 12.0 to 25.0 % and 53.0 to 58.0 % for treated and control dogs respectively (P< 0.0001. The blood feeding inhibition was 75.0–87.0 % and 41.0–46.0 % for the control and treated dogs (P< 0.0001, respectively.The total mortality rate was 94.0–100 % and 19.0–58.0 % respectively for the treated and control groups (P< 0.001.Conclustion: Application of pour-on flumethrin on dogs caused 90–100 % mortality until 2.5 month and inhibited the blood-feeding of sand flies. 

  10. Diagnosis of Leishmaniasis

    ... please visit this page: About CDC.gov . Parasites - Leishmaniasis Parasites Home Share Compartir Diagnosis Light-microscopic examination ... bone marrow specimen from a patient with visceral leishmaniasis—showing a macrophage (a special type of white ...

  11. Diminished CD4+/CD25+ T cell and increased IFN-gamma levels occur in dogs vaccinated with Leishmune in an endemic area for visceral leishmaniasis.

    de Lima, Valéria Marçal Felix; Ikeda, Fabiana Augusta; Rossi, Cláudio N; Feitosa, Mary Marcondes; Vasconcelos, Rosemeride Oliveira; Nunes, Caris Maroni; Goto, Hiro

    2010-06-15

    The Leishmune vaccine has been used in endemic areas to prevent canine visceral leishmaniasis in Brazil, but cytokine production induced by vaccination has rarely been investigated in dogs. This study aimed to evaluate the immune response of dogs vaccinated with Leishmune FML vaccine (Fort Dodge) against total antigen of Leishmania (Leishmania) chagasi (TAg) and FML. Twenty healthy dogs from Araçatuba, São Paulo, Brazil, an endemic leishmaniasis area, received three consecutive subcutaneous injection of Leishmune vaccine at 21-day intervals. PBMC were isolated before and 10 days after completing vaccination and lymphoproliferative response and antibody production against FML or total promastigote antigen were tested. Cytokines IFN-gamma, IL-4 and TNF-alpha were measured in culture supernatant and CD4+/CD25+ and CD8+/CD25+ T cell presence was determined. Analysis of the data indicated that the vaccine conferred humoral responses (100%) against both antigens and cellular immunity to FML (85%) and total antigen (80%), the supernatant of cultured cells stimulated with TAg and FML showed an increase in IFN-gamma (P<0.05), and the vaccine reduced CD4+/CD25+ T cell presence compared to that observed before vaccination. These responses may constitute part of the immune mechanism induced by Leishmune. PMID:20132994

  12. Evaluation of enzyme-linked immunosorbent assay using crude Leishmania and recombinant antigens as a diagnostic marker for canine visceral leishmaniasis

    Eliza Yoshie do Rosário

    2005-04-01

    Full Text Available The performances of ELISA assays with different antigen preparations, such as Leishmania amazonensis or L. chagasi lysates and the recombinant antigens rK-39 and rK-26, were compared using sera or eluates from dried blood collected on filter paper to detect anti-Leishmania antibodies in dogs from a visceral leishmaniasis-endemic area in Brazil. Of 115 IFAT-reactive dogs at 1:40 titre, 106 (92.2% were positive in parasitological exams (skin and/or spleen. These animals were compared to healthy animals (n = 25, negative for IFAT at a titre of 1:40 and parasitological exams. The sensitivities of crude and recombinant antigens were similar and remarkably high for both sera and eluates (97-100%. Specificity was higher than 96% for sera and eluates for different antigens, except for L. chagasi antigen using eluates (88%. Concordance values among the tests were higher either for sera or eluates (J = 0.95-1.00. High concordances were observed between sera and eluates tested with different antigens (kappa = 0.93-0.97. Crude and recombinant antigens identified different clinical phases of canine leishmaniasis. These results show that eluates could be used in canine surveys to identify L. chagasi infection. Recombinant antigens added little when compared to crude antigen in identifying positive dogs. Cross-reactivity with other diseases whose distribution often overlaps VL-endemic areas is a limitation of crude antigen use however.

  13. Cloning and characterization of a V-ATPase subunit C from the American visceral leishmaniasis vector Lutzomyia longipalpis modulated during development and blood ingestion.

    Ramalho-Ortigão, J M; Pitaluga, A N; Telleria, E L; Marques, C; Souza, A A; Traub-Cseko, Y M

    2007-06-01

    Visceral leishmaniasis (VL) is a serious tropical disease that affects approximately 500 thousand people worldwide every year. In the Americas, VL is caused by the parasite Leishmania (Leishmania) infantum chagasi mainly transmitted by the bite of the sand fly vector Lutzomyia longipalpis. Despite recent advances in the study of interaction between Leishmania and sand flies, very little is known about sand fly protein expression profiles. Understanding how the expression of proteins may be affected by blood feeding and/or presence of parasite in the vector's midgut might allow us to devise new strategies for controlling the spread of leishmaniasis. In this work, we report the characterization of a vacuolar ATPase subunit C from L. longipalpis by screening of a midgut cDNA library with a 220 bp fragment identified by means of differential display reverse transcriptase-polymerase chain reaction analysis. The expression of the gene varies along insect development and is upregulated in males and bloodfed L. longipalpis, compared to unfed flies. PMID:17607496

  14. Cloning and characterization of a V-ATPase subunit C from the American visceral leishmaniasis vector Lutzomyia longipalpis modulated during development and blood ingestion

    JM Ramalho-Ortigão

    2007-06-01

    Full Text Available Visceral leishmaniasis (VL is a serious tropical disease that affects approximately 500 thousand people worldwide every year. In the Americas, VL is caused by the parasite Leishmania (Leishmania infantum chagasi mainly transmitted by the bite of the sand fly vector Lutzomyia longipalpis. Despite recent advances in the study of interaction between Leishmania and sand flies, very little is known about sand fly protein expression profiles. Understanding how the expression of proteins may be affected by blood feeding and/or presence of parasite in the vector's midgut might allow us to devise new strategies for controlling the spread of leishmaniasis. In this work, we report the characterization of a vacuolar ATPase subunit C from L. longipalpis by screening of a midgut cDNA library with a 220 bp fragment identified by means of differential display reverse transcriptase-polymerase chain reaction analysis. The expression of the gene varies along insect development and is upregulated in males and bloodfed L. longipalpis, compared to unfed flies.

  15. Investigação de áreas de risco como metodologia complementar ao controle da leishmaniose visceral canina Investigation of risk areas as complemental methodology for the control of canine visceral leishmaniasis

    Fred S. Julião

    2007-08-01

    Full Text Available Foram investigadas áreas de risco de leishmaniose visceral canina no município de Camaçari, Bahia. Um total de 278 cães distribuídos em 141 residências, pertencentes a 20 áreas de risco investigadas, foi examinado sorologicamente (ELISA. A soroprevalência geral foi 21,7% (56/258 depois da exclusão dos 20 cães usados no início do estudo para delimitar a área. Os resultados respectivos das análises univariada e multivariada dos fatores relacionados à infecção do cão por Leishmania chagasi, a captura e distribuição do vetor na área e a metodologia usada para localizar os focos caninos são discutidos.Risk areas of canine visceral leishmaniasis in the city of Camaçari, Bahia, Brazil, were investigated. A total of 278 dogs from 141 homes pertaining to 20 investigated risk areas was serologically screened (ELISA. The general seroprevalence was 21.7% (56/258 after exclusion of 20 dogs used at the beginning of the survey to limit the study area. The respective results of the univariated and multivariated analysis of factors related to infection of dogs by Leishmania chagasi, to vector distribu-tion pattern in the area and to the methodology used to localize the canine focuses are discussed.

  16. Autochthonous canine visceral leishmaniasis in a non-endemic area: Bom Sucesso, Minas Gerais State, Brazil Ocorrência de leishmaniose visceral canina autóctone em uma área não-endêmica: Bom Sucesso, Minas Gerais, Brasil

    Marcio Roberto Silva

    2008-02-01

    Full Text Available The article begins by describing a dog with characteristic symptoms of visceral leishmaniasis. A serum sample from this animal was positive by indirect immunofluorescence (IIF performed in anti-Leishmania total IgG in 1999. Tissues from the same dog were also positive by polymerase chain reaction (PCR in 2004, identifying Leishmania DNA in the cerebellum, liver, kidney, and intestine. This is the first report of a dog with autochthonous visceral leishmaniasis in the county of Bom Sucesso, Minas Gerais State, Brazil. The finding of this IIF-positive dog led to a canine visceral leishmaniasis epidemiological investigation in the county. The investigation was conducted from March 1999 to December 2005. IIF was positive for Leishmania in 22 (3% of 734 examined dogs. Among the 22 IIF-positive dogs, six presented characteristic symptoms of canine visceral leishmaniasis. The results of this epidemiological investigation were sent to local and State public health authorities, requesting visceral leishmaniasis control and preventive measures to interrupt transmission of the disease and avoid the occurrence of human cases.O presente trabalho descreve inicialmente um cão com sintomas característicos de leishmaniose visceral. Amostra de soro desse cão foi positiva por imunofluorescência indireta (IFI conduzida no IgG total anti-Leishmania em 1999. Além disso, tecidos desse cão foram positivos por reação em cadeia pela polimerase (PCR conduzida em 2004, identificando DNA de Leishmania no cerebelo, fígado, rim e intestino. Esta é a primeira vez que um cão com leishmaniose visceral autóctone foi descrito no Município de Bom Sucesso, Minas Gerais, Brasil. O achado desse cão reagente à IFI levou a uma investigação epidemiológica nesse município. Essa investigação foi conduzida de março de 1999 a dezembro de 2005. Vinte e dois de um total de 734 (3% cães examinados foram reagentes à IFI. Entre os 22 cães IFI reagentes, seis apresentaram

  17. Leishmaniasis in the knee area

    Bava Amadeo Javier; Rossi Maria Laura; Seley Celeste; Troncoso Alcides

    2010-01-01

    Leishmaniasis is a parasitic infection caused by species leishmaniae, which can produce two types of manifestations: visceral and cutaneous. In south America cutaneous leishmaniasis is more common than visceral leishmaniasis. A case of primary cutaneous leishmaniasis from Bolivia is presented for its rarity. The patient of our case showed an ulcerated lesion of the knee. Montenegro's intradermal test was positive. Giemsa-stained touch preparation of the skin biopsy revealed amastigotes inside macrophages, consistent with leishmaniasis. The patient was treated with meglumine antimoniate intramuscular (20 mg of Sb+/kg/day) three weeks, with complete cicatrization of the lesion.

  18. Drug Resistance in Leishmaniasis

    Croft, Simon L.; Sundar, Shyam; Fairlamb, Alan H.

    2006-01-01

    Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients with visceral leishmaniasis in Bihar State, India, do not respond to treatment with pentavalent antimo...

  19. Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis.

    Sowmya Pattabhi

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is diagnosed by microscopic confirmation of the parasite in bone marrow, spleen or lymph node aspirates. These procedures are unsuitable for rapid diagnosis of VL in field settings. The development of rK39-based rapid diagnostic tests (RDT revolutionized diagnosis of VL by offering high sensitivity and specificity in detecting disease in the Indian subcontinent; however, these tests have been less reliable in the African subcontinent (sensitivity range of 75-85%, specificity of 70-92%. We have addressed limitations of the rK39 with a new synthetic polyprotein, rK28, followed by development and evaluation of two new rK28-based RDT prototype platforms. METHODOLOGY/PRINCIPAL FINDINGS: Evaluation of 62 VL-confirmed sera from Sudan provided sensitivities of 96.8% and 93.6% (95% CI = K28: 88.83-99.61%; K39: 84.30-98.21% and specificities of 96.2% and 92.4% (95% CI = K28: 90.53-98.95%; K39: 85.54-96.65% for rK28 and rK39, respectively. Of greater interest was the observation that individual VL sera with low rK39 reactivity often had much higher rK28 reactivity. This characteristic of the fusion protein was exploited in the development of rK28 rapid tests, which may prove to be crucial in detecting VL among patients with low rK39 antibody levels. Evaluation of two prototype lateral flow-based rK28 rapid tests on 53 VL patients in Sudan and 73 VL patients in Bangladesh provided promisingly high sensitivities (95.9% [95% CI = 88.46-99.1 in Sudan and 98.1% [95% CI = 89.93-99.95%] in Bangladesh compared to the rK39 RDT (sensitivities of 86.3% [95% CI = 76.25-93.23%] in Sudan and 88.7% [95% CI = 76.97-95.73%] in Bangladesh. CONCLUSIONS/SIGNIFICANCE: Our study compares the diagnostic accuracy of rK39 and rK28 in detecting active VL cases and our findings indicate that rK28 polyprotein has great potential as a serodiagnostic tool. A new rK28-based RDT will prove to be a valuable asset in

  20. Antigenicity, Immunogenicity and Protective Efficacy of Three Proteins Expressed in the Promastigote and Amastigote Stages of Leishmania infantum against Visceral Leishmaniasis.

    Vivian Tamietti Martins

    Full Text Available In the present study, two Leishmania infantum hypothetical proteins present in the amastigote stage, LiHyp1 and LiHyp6, were combined with a promastigote protein, IgE-dependent histamine-releasing factor (HRF; to compose a polyproteins vaccine to be evaluated against L. infantum infection. Also, the antigenicity of the three proteins was analyzed, and their use for the serodiagnosis of canine visceral leishmaniasis (CVL was evaluated. The LiHyp1, LiHyp6, and HRF DNA coding sequences were cloned in prokaryotic expression vectors and the recombinant proteins were purified. When employed in ELISA assays, all proteins were recognized by sera from visceral leishmaniasis (VL dogs, and presented no cross-reactivity with either sera from dogs vaccinated with a Brazilian commercial vaccine, or sera of Trypanosoma cruzi-infected or Ehrlichia canis-infected animals. In addition, the antigens were not recognized by antibodies from non-infected animals living in endemic or non-endemic areas for leishmaniasis. The immunogenicity and protective efficacy of the three proteins administered in the presence of saponin, individually or in combination (composing a polyproteins vaccine, were evaluated in a VL murine model: BALB/c mice infected with L. infantum. Spleen cells from mice inoculated with the individual proteins or with the polyproteins vaccine plus saponin showed a protein-specific production of IFN-γ, IL-12, and GM-CSF after an in vitro stimulation, which was maintained after infection. These animals presented significant reductions in the parasite burden in different evaluated organs, when compared to mice inoculated with saline or saponin. The decrease in parasite burden was associated with an IL-12-dependent production of IFN-γ against parasite total extracts (produced mainly by CD4+ T cells, correlated to the induction of parasite proteins-driven NO production. Mice inoculated with the recombinant protein-based vaccines showed also high levels of

  1. Mapping B-cell epitopes for the peroxidoxin of Leishmania (Viannia braziliensis and its potential for the clinical diagnosis of tegumentary and visceral leishmaniasis.

    Daniel Menezes-Souza

    Full Text Available The search toward the establishment of novel serological tests for the diagnosis of leishmaniasis and proper differential diagnosis may represent one alternative to the invasive parasitological methods currently used to identify infected individuals. In the present work, we investigated the potential use of recombinant peroxidoxin (rPeroxidoxin of Leishmania (Viannia braziliensis as a potential antigen for the immunodiagnosis of human tegumentary (TL and visceral leishmaniasis (VL and canine visceral leishmaniasis (CVL. Linear B-cell epitope mapping was performed to identify polymorphic epitopes when comparing orthologous sequences present in Trypanosoma cruzi, the agent for Chagas disease (CD, and the Homo sapiens and Canis familiaris hosts. The serological assay (ELISA demonstrated that TL, VL and CVL individuals showed high levels of antibodies against rPeroxidoxin, allowing identification of infected ones with considerable sensitivity and great ability to discriminate (specificity between non-infected and CD individuals (98.46% and 100%; 98.18% and 95.71%; 95.79% and 100%, respectively. An rPeroxidoxin ELISA also showed a greater ability to discriminate between vaccinated and infected animals, which is an important requirement for the public campaign control of CVL. A depletion ELISA assay using soluble peptides of this B-cell epitope confirmed the recognition of these sites only by Leishmania-infected individuals. Moreover, this work identifies two antigenic polymorphic linear B-cell epitopes of L. braziliensis. Specific recognition of TL and VL patients was confirmed by significantly decreased IgG reactivity against rPeroxidoxin after depletion of peptide-1- and peptide-2-specific antibodies (peptide 1: reduced by 32%, 42% and 5% for CL, ML and VL, respectively; peptide-2: reduced by 24%, 22% and 13% for CL, ML and VL, respectively and only peptide-2 for CVL (reduced 9%. Overall, rPeroxidoxin may be a potential antigen for the

  2. A review of Leishmaniasis in Eastern Africa

    Peter K. Ngure; Albert Kimutai; Zipporah W. Ng'ang'a; Geoffrey Rukunga; Willy K. Tonui

    2009-01-01

    The review presents the epidemiology of leishmaniasis in the Eastern Africa region. We searched PUB MED and MEDLINE with several key words-namely,"leishmaniasis";"cutaneous"," diffuse cutaneous"," mucosal", and "visceral leishmaniasis";"kala azar" and "post kala azar dermal leishmaniasis"-for recont clinical and basic science articles related to leishmaniasis in countries in the Eastern Africa region. Poverty, wars, conflicts and migration have significantly aggravated leishmaniases in Eastern Africa. Of particular concern is the increasing incidence of Leishmania-HIV co-infection in Ethiopia where 20--40% of the persons affected by visceral leishmaniasis are HIV-co-infected. Sudan has the highest prevalence rate of post kala-azar dermal leishmaniasis(PKDL) in the world, a skin complication of visceral leishmaniasis(VL) that mainly afflicts children below age ten. In view of its spread to previously non-endemic areas and an increase in imported cases, leishmaniasis in Eastern Africa should be considered a health emergency.

  3. Assessment of the Effects of a Novel Herbal Immunomodulator Drug (IMOD on Cytokine Profiles in Experimental Canine Visceral Leishmaniasis: a Preliminary Survey.

    Abdolali Malmasi

    2014-09-01

    Full Text Available Cytokines play a fundamental role in the regulation of immune responses in remission and/or relapsing of leishmaniasis. Therefore, immunotherapy for the treatment of canine visceral leishmaniasis (CVL has represented a principle approach in control of the infection. The present research aimed to evaluating the immunotherapeutic potential of a novel herbal immunomodulator drug (IMOD on CVL.Twelve mongrel dogs were intravenously infected with Iranian strain of L. infantum and randomly divided into three groups; 1: negative control (non-infected, 2: immunotherapy with IMOD and 3: positive control (non-treated. Cell proliferation and Th1-/Th2-type cytokines were measured in peripheral blood mononuclear cell (PBMC by cell proliferation kit I (MTT and enzyme-linked immunospot (ELISpot assays, respectively.At the 60 days follow-up assessment, no adverse effects were observed in treated interventional group. Cellular proliferation assay indicated that PBMCs of IMOD group had higher stimulation index (SI than positive control group (p < 0.05. Enhancement of CD4+T cells such as IL-2, IL-4 & IL-10 were detected in negative control group due to in vitro IMOD stimulation 30 days post-treatment. In accordance to decreasing trends of Th1 & Th2 cytokines in positive control group, the mean number of IFN-γ IL-2, IL-4 and IL-10 spot forming cells (SFCs down regulated for IMOD group during the study.These data indicate that IMOD had immunomodulatory potential but is not sufficient for total parasitic cure due to balance of Th1/Th2 cytokines. This is a preliminary study and we propose to undertake a series of experiments to evaluate the CVL due to in vitro modulatory effects of IMOD.

  4. Immucillins ImmA and ImmH Are Effective and Non-toxic in the Treatment of Experimental Visceral Leishmaniasis.

    Elisangela Oliveira Freitas

    2015-12-01

    Full Text Available Immucillins ImmA (IA, ImmH (IH and SerMe-ImmH (SMIH are synthetic deazapurine nucleoside analogues that inhibit Leishmania (L. infantum chagasi and Leishmania (L. amazonensis multiplication in vitro without macrophage toxicity. Immucillins are compared to the Glucantime standard drug in the chemotherapy of Leishmania (L. infantum chagasi infection in mice and hamsters. These agents are tested for toxicity and immune system response.BALB/c mice were infected with 107 amastigotes, treated with IA, IH, SMIH or Glucantime (2.5mg/kg/day and monitored for clinical variables, parasite load, antibody levels and splenocyte IFN-γ, TNF-α, and IL-10 expression. Cytokines and CD4+, CD8+ and CD19+ lymphocyte frequencies were assessed in uninfected controls and in response to immucillins. Urea, creatinine, GOT and GPT levels were monitored in sera. Anti-Leishmania-specific IgG1 antibodies (anti-NH36 increased in untreated animals. IgG2a response, high levels of IFN-γ, TNF-α and lower levels of IL-10 were detected in mice treated with the immucillins and Glucantime. Immucillins permitted normal weight gain, prevented hepato-splenomegaly and cleared the parasite infection (85-89% without renal and hepatic toxicity. Immucillins promoted 35% lower secretion of IFN-γ in uninfected controls than in infected mice. IA and IH increased the CD4+ T and CD19+ B cell frequencies. SMIH increased only the proportion of CD-19 B cells. IA and IH also cured infected hamsters with lower toxicity than Glucantime.Immucillins IA, IH and SMIH were effective in treating leishmaniasis in mice. In hamsters, IA and IH were also effective. The highest therapeutic efficacy was obtained with IA, possibly due to its induction of a TH1 immune response. Low immucillin doses were required and showed no toxicity. Our results disclose the potential use of IA and IH in the therapy of visceral leishmaniasis.

  5. Laryngeal Leishmaniasis

    Moraes, Bruno Teixeira de

    2012-01-01

    Full Text Available Introduction: Leishmaniasis is classified into three clinical presentations: visceral, coetaneous and mucocutaneous. The latter is usually secondary to hematogenous spread after months or years of skin infection and can manifest as infiltrative lesions, ulcerated or vegetating in nose, pharynx, larynx and mouth, associated or not with ganglionics infarction. Laryngeal involvement is part of the differential diagnosis of lesions in this topography as nonspecific chronic laryngitis, granulomatosis and even tumors of the upper aerodigestive tract presenting atypical evolution. Sometimes it is difficult for the correct diagnosis of Leishmaniasis, with description of cases in the literature were conducted improperly. Objective: The objective of this study is to report a case of laryngeal Leishmaniasis addressing the difficulty of diagnosis, complications and treatment applied. Case Report: A patient with pain throat, dysphagia, odynophagia, dysphonia and weight loss, with no improvement with symptomatic medication. At telelaringoscopy, infiltrative lesion showed nodular supraglottis. He underwent a tracheotomy for airway obstruction and biopsy with immunohistochemical study for a definitive diagnosis of laryngeal Leishmaniasis. The patient was referred to the infectious diseases that initiated treatment with N-methylglucamine antimoniate with satisfactory response to therapy. Final Comments: Faced with a clinical suspicion of granulomatous diseases, it is essential to follow protocol laboratory evaluation associated with histological injury, to get a precise definition etiological without prolonging the time of diagnosis. Medical treatment for mucosal Leishmaniasis, recommended by the World Health Organization, was adequate in the case of laryngeal disorders, with complete resolution of symptoms.

  6. Aspectos epidemiológicos da leishmaniose visceral canina no município de Pedro Leopoldo, Minas Gerais, 2003 Epidemiologic aspects of canine visceral leishmaniasis in Pedro Leopoldo district, Minas Gerais, 2003

    L.A.B. Naveda

    2006-12-01

    Full Text Available Determinou-se a prevalência da leishmaniose visceral canina (LVC no município de Pedro Leopoldo, MG, 2003, por meio de inquérito soro-epidemiológico. Coletaram-se amostras de sangue de 2.185 cães e aplicou-se questionário semi-estruturado em cada residência. Os animais foram divididos em quatro grupos, sendo o grupo A constituído de 1240 cães das áreas urbana e rural; o grupo B de 705 cães de áreas em torno dos focos; o grupo C, de 134 cães, cujas amostras foram coletadas durante o dia da vacinação anti-rábica oficial; e o grupo D composto de 111 cães errantes. Os dados foram armazenados em banco de dados EPIINFO 6.04b. Os 36 cães positivos foram localizados espacialmente com auxílio de GPS (Global Positioning System, e o georreferenciamento realizado por meio do programa AUTOCAD 2000. A prevalência global da LVC foi de 1,4% e variou de 1,1% na área urbana e 4,2% na rural. Estes resultados permitiram concluir que Pedro Leopoldo, de acordo com a classificação oficial do Ministério da Saúde, é área silenciosa, receptiva e vulnerável para LVC. A distribuição espacial dos casos é diferenciada e requer medidas sanitárias de acordo com cada área de risco.The prevalence of canine visceral leishmaniasis (CVL in Pedro Leopoldo district, 2003 was evaluated. A serum-epidemic inquiry was accomplished by collecting blood samples of dogs and by applying a semi structured questionnaire, according to groups, in each visited residence: group A, constituted of 1240 dogs of the urban and rural areas; group B, constituted of 705 dogs sampled around the focuses; group C, constituted of 134 dogs, wich samples were collected during the canine/feline antirabic vaccination; and group D, constituted of 111 wandering dogs. The data were stored in the EPI INFO 6.04b database. Positive dogs were spatially located using GPS (Global Positioning System and the geographycal reference was made through the AUTOCAD 2000 program. The district global

  7. Regulatory IgDhi B Cells Suppress T Cell Function via IL-10 and PD-L1 during Progressive Visceral Leishmaniasis.

    Schaut, Robert G; Lamb, Ian M; Toepp, Angela J; Scott, Benjamin; Mendes-Aguiar, Carolina O; Coutinho, Jose F V; Jeronimo, Selma M B; Wilson, Mary E; Harty, John T; Waldschmidt, Thomas J; Petersen, Christine A

    2016-05-15

    During visceral leishmaniasis (VL), Th1-based inflammation is induced to control intracellular parasites. Inflammation-based pathology was shown to be dampened by IL-10 and eventual programmed death 1-mediated T cell exhaustion. Cell type(s) responsible for the initiation of T cell-produced IL-10 during VL are unknown. CD19(+), CD5(-), CD1d(-), IgD(hi) regulatory B cells from healthy controls produced IL-10 in the absence of infection or stimulation, in contrast to IgD(lo/neg) B cells. IgD(hi) B cells may have a de novo versus induced regulatory program. The population of IgD(hi) B cells increased 3-fold as VL progressed. B cells from VL dogs were necessary and sufficient to suppress Th1 cell effector function. IgD(hi) B cells induced IL-10 production by T cells and IgD(lo) B cells. Blockage of B cell-specific PD-L1 restored Th1 responses. IgD(hi) regulatory B cells represent a novel regulatory B cell that may precipitate T cell exhaustion during VL. PMID:27076677

  8. Identification of environmental parameters and risk mapping of visceral leishmaniasis in Ethiopia by using geographical information systems and a statistical approach

    Teshome Tsegaw

    2013-05-01

    Full Text Available Visceral leishmaniasis (VL, a vector-borne disease strongly influenced by environmental factors, has (re-emerged in Ethiopia during the last two decades and is currently of increasing public health concern. Based on VL incidence in each locality (kebele documented from federal or regional health bureaus and/or hospital records in the country, geographical information systems (GIS, coupled with binary and multivariate logistic regression methods, were employed to develop a risk map for Ethiopia with respect to VL based on soil type, altitude, rainfall, slope and temperature. The risk model was subsequently validated in selected sites. This environmental VL risk model provided an overall prediction accuracy of 86% with mean land surface temperature and soil type found to be the best predictors of VL. The total population at risk was estimated at 3.2 million according to the national population census in 2007. The approach presented here should facilitate the identification of priority areas for intervention and the monitoring of trends as well as providing input for further epidemiological and applied research with regard to this disease in Ethiopia.

  9. The Seminested PCR Based Detection of Leishmania infantum Infection in Asymptomatic Dogs in a New Endemic Focus of Visceral Leishmaniasis in Iran

    Y Rassi

    2007-06-01

    Full Text Available Visceral Leishmaniasis (Kala-azar is a serious health problem in some northern and south western parts of Iran. The incidence of kala-azar caused by Leishmania infantum has recently increased in Nourabad-Mamassani district of Fars Province, in the south of the country. This study was designed to determine the role of asymptomatic dogs as host reservoir of L. infantum in this new formed focus and detection of prevalence of infection near them. A total of 20 as¬ymptomatic stray and sheep dogs were randomly sampled. The Buffy coat layer of their peripheral blood was used for DNA extraction and PCR. A species specific seminested PCR was used for DNA amplification using LINR4, LIN17 and LIN19 primers. These primers amplified variable area of the minicircle kDNA of Leishmania parasites. Of the 20 sampled dogs checked for leishmanial kDNA, six (30% were found naturally infected. It is concluded that, dogs (Canis familiaris even if asympto¬matic, is considered as the domestic host reservoir of kala-azar in this endemic focus.

  10. Human and canine visceral leishmaniasis in an emerging focus in Araçuaí, Minas Gerais: spatial distribution and socio-environmental factors

    Ursine, Renata Luiz; Dias, João Victor Leite; Morais, Harriman Aley; Pires, Herton Helder Rocha

    2016-01-01

    This study aimed to analyse the spatial distribution of human (2007-2013) and canine (2013) visceral leishmaniasis (VL) in the city of Araçuaí, Minas Gerais, Brazil, and identify the socio-environmental factors related to their occurrence. The spatial distribution of human and canine cases was analysed by kernel density estimation (KDE) and the K function. The KDE values were analysed for correlation between human and canine LV and for normalised difference vegetation index (NDVI). Socio-environmental aspects of household structures and surroundings were evaluated. The spatial distribution of human and canine VL cases exhibited a significant aggregated pattern in distances greater than 350 and 75 m, respectively. The higher occurrence of human and canine infection occurred in the central area of the city. A positive correlation between the densities of human and canine cases was observed, as well as a negative correlation between NDVI and densities of human and canine cases. Socio-environmental analysis revealed that the large amount of animals, organic material from trees and deficiencies in environmental sanitation are possibly contributing to the continuation of the transmission cycle of Leishmania infantum in Araçuaí. These results can contribute to the planning by competent agencies to reduce the incidence of infection in the city. PMID:27384080

  11. Distribution of phlebotomine fauna (Diptera: Psychodidae across an urban-rural gradient in an area of endemic visceral leishmaniasis in northern Brazil

    Davi Marcos Souza de Oliveira

    2011-12-01

    Full Text Available The number of visceral leishmaniasis (VL cases has increased over the past 10 years in Brazil, especially in the North and Northeast regions of the country. The aim of this study was to evaluate the urbanisation of VL vectors in Barcarena, Pará, an area in northern Brazil where VL is endemic. Sandflies were captured using Centers for Disease Control (CDC light traps along an urban-rural gradient. The CDC traps were installed inside hen houses at a height of 150 cm. A total of 5,089 sandflies were collected and 11 species were identified. The predominant species was Lutzomyia longipalpis (rate of 95.15%, which suggests its participation in the transmission of VL. A total of 1,451 Lu. longipalpis females were dissected and no Leishmania infections were detected. Most of the sandflies were captured at the border of a forest (88.25% and no flies were captured in the urban area, which suggests that transmission is still restricted to rural sites. However, the fact that a specimen was collected in an intermediate area indicates that urbanisation is a real possibility and that vector monitoring is important.

  12. Physiological Age Structure and Leishmania spp. Detection in Phlebotomus (Larroussius orientalis (Parrot, 1936 (Diptera: Psychodidae at an Endemic Focus of Visceral Leishmaniasis in Northern Ethiopia

    Araya Gebresilassie

    2015-01-01

    Full Text Available Visceral leishmaniasis (VL caused by Leishmania donovani is endemic in northern Ethiopia, where P. orientalis is the most important presumed vector. This study was designed to determine the physiological age structure and the occurrence of Leishmania infection in the vector of VL in Tahtay Adiyabo district, northern Ethiopia. Sand flies were collected using CDC light traps from peridomestic and agricultural fields between May 2011 and April 2012 and P. orientalis females were dissected for age determination and detection of Leishmania promastigotes. Sand flies were also analyzed for L. donovani detection using molecular methods. Of 1,282 P. orientalis examined for abdominal stages and age characterization, 66.2%, 28.2%, 4.1%, and 1.6% were unfed, freshly fed, half-gravid, and gravid. Parous rate in unfed females was 34.1% and 35.4% in peridomestic and agricultural fields, respectively. Out of 921 P. orientalis females dissected, one specimen (0.1% was found naturally infected with promastigotes. Five pools (25 females of unfed P. orientalis were also found with DNA of Leishmania spp. In particular, a single P. orientalis was positive for L. donovani (0.5%. Based on this and other evidences (abundance, human blood feeding, and xenodiagnostic studies, P. orientalis is the principal vector of VL in this endemic focus.

  13. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis

    Shahbazi, Mehdi; Zahedifard, Farnaz; Taheri, Tahereh; Taslimi, Yasaman; Jamshidi, Shahram; Shirian, Sadegh; Mahdavi, Niousha; Hassankhani, Mehdi; Daneshbod, Yahya; Zarkesh-Esfahani, Sayyed Hamid; Papadopoulou, Barbara; Rafati, Sima

    2015-01-01

    Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL. PMID:26197085

  14. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.

    Mehdi Shahbazi

    Full Text Available Canine Visceral Leishmaniasis (CVL is a major veterinary and public health problem caused by Leishmania infantum (L. infantum in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL.

  15. SLA-PGN-primed dendritic cell-based vaccination induces Th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of PKCβ.

    Jawed, Junaid Jibran; Majumder, Saikat; Bandyopadhyay, Syamdas; Biswas, Satabdi; Parveen, Shabina; Majumdar, Subrata

    2016-07-01

    Emergence of drug resistance during visceral leishmaniasis (VL) is a major obstacle imposed during successful therapy. An effective vaccine strategy against this disease is therefore necessary. Our present study exploited the SLA (soluble leishmanial antigen) and PGN (peptidoglycan) stimulated bone marrow-derived dendritic cells (DCs) as a suitable vaccine candidate during experimental VL. SLA-PGN-stimulated DCs showed a significant decrease in hepatic and splenic parasite burden, which were associated with increased production of nitric oxide and pro-inflammatory cytokines such as IL-12, IFN-γ and IL-17. Elevated level of IL-17 was accompanied with the generation of more Th17 cells. Further studies on DC provided the evidence that these SLA-PGN-stimulated DCs played an important role in providing necessary cytokines such as IL-6, IL-23 and TGF-β for the generation of Th17 cells. Interestingly, inhibition of protein kinase C-β (PKCβ) in DCs led to decreased production of Th17 polarizing cytokines, causing reduction of the Th17 population size. Altogether, our finding highlighted the important role of DC-based PKCβ in regulation of the function and generation of Th17 cells. PMID:27150838

  16. Flebotomíneos de áreas com notificações de casos autóctones de leishmaniose visceral canina e leishmaniose tegumentar americana em Angra dos Reis, Rio de Janeiro, Brasil Phlebotomine fauna in areas of autochthonous cases of canine visceral leishmaniasis and American cutaneous leishmaniasis in Angra dos Reis, Rio de Janeiro, Brazil

    Marcos Barbosa de Souza

    2009-01-01

    Full Text Available Flebótomos de áreas com notificações de casos autóctones de leishmaniose visceral canina e leishmaniose tegumentar americana em Angra dos Reis, Rio de Janeiro, Brasil. O município de Angra dos Reis apresenta casos humanos de leishmaniose tegumentar americana desde 1945. Inquéritos flebotomínicos realizados em 1978 revelaram a presença de Nyssomyia intermedia e a primeira notificação de Lutzomyia longipalpis no Rio de Janeiro, Ilha Grande, Angra dos Reis. Em agosto de 2002 foi notificado o primeiro caso canino de leishmaniose visceral na Ilha Grande, Angra dos Reis. Inquéritos flebotomínicos realizados nos peridomicílios, no período de novembro de 2002 a maio de 2003, em quatro localidades de Angra dos Reis, resultaram em 12.554 flebotomíneos e a presença de nove espécies: Brumptomyia sp.; Nyssomyia intermedia, Migonemyia migonei, Micropygomyia schreiberi, Pintomyia fischeri, Psychodopygus davisi, Psychodopygus ayrosai, Evandromyia tupinambay, Psathyromyia pelloni. foi Nyssomyia intermedia, predominante em todas as localidades, seguida por M.migonei. O principal vetor da LVA, Lutzomyia longipalpis, não foi detectado nas localidades, incluindo áreas do entorno, onde um cão infectado residia.The city of Angra dos Reis presents human cases of American cutaneous leishmaniasis since 1945. Phlebotomine surveys in 1978 had disclosed the presence of Nyssomyia intermedia and the first notification of Lutzomyia longipalpis in Rio de Janeiro, Ilha Grande, Angra dos Reis. In August of 2002 the first canine case of visceral leishmaniasis in the Ilha Grande, Angra dos Reis was notified. Surveys of phlebotomines in the peridomiciliary areas, in the period of November, 2002, through May, 2003, in four localities of Angra dos Reis, resulted in 12,554 specimens belonging to nine species: Brumptomyia sp. Nyssomyia intermedia, Migonemyia migonei, Micropygomyia schreiberi, Pintomyia fischeri, Psychodopygus davisi, Psychodopygus ayrosai

  17. Presence of Circulating Levels of Interferon-g, Interleukin-10 and Tumor Necrosis Factor-a in Patients with Visceral Leishmaniasis

    Iara Marques de MEDEIROS

    1998-01-01

    Full Text Available Experimental murine L. major infection is characterized by the expansion of distinct CD4+ T cell subsets. The Th1 response is related to production of IFN-g and resolution of infection, whereas Th-2 response with production of IL-4 and IL-10 and dissemination of infection. The objective of this study was to measure the circulating levels of IFN-g, IL-10 and TNF-a in patients with visceral leishmaniasis (VL before, during and at the end of therapy and to examine the association between cytokine levels and activity of VL. Fifteen patients with VL were evaluated. The cytokine determinations were done by using the enzyme-linked immunoassay (ELISA before, during and at the end of therapy. At baseline, we detected circulating levels of IFN-g in 13 of 15 patients (median = 60 pg/ml; IL-10 in 14 of 15 patients (median = 141.4 pg/ml; and TNF-a in 13 of 14 patients (median = 38.9 pg/ml. As patients improved, following antimonial therapy, circulating levels of IL-10 showed an exponential decay (y = 82.34 e–0,10367x, r = –0.659; p g was no longer detected after 7/14 days of therapy. On the other hand, circulating levels of TNF-a had a less pronounced decay with time on therapy, remaining detectable in most patients during the first seven days of therapy (y = 36.99-0.933x, r = –0.31; p = 0.05. Part of the expression of a successful response to therapy may, therefore, include reduction in secretion of inflammatory as well as suppressive cytokines. Since IL-10 and IFN-g are both detected prior to therapy, the recognized cellular immune depression seen in these patients may be due to biological predominance of IL-10 (type 2 cytokine, rather than lack of IFN-g (type 1 cytokine production.Infecção murina experimental por L. major caracteriza-se pela expansão de subpopulações distintas de células T CD4+. A resposta Th-1 relaciona-se com a produção de IFN-g e resolução da infecção, enquanto a resposta Th-2 com a produção de IL-4 e IL-10 e

  18. Frequência de autoanticorpos e dosagem de complemento sérico em pacientes com diagnóstico de leishmaniose cutânea ou visceral Frequency of autoantibodies and serum complement levels in patients with visceral or cutaneous leishmaniasis

    Alex Magno Coelho Horimoto

    2009-10-01

    êmica predominantemente humoral do tipo Th2, constituindo-se em diagnóstico diferencial obrigatório com LES, principalmente nas áreas endêmicas.INTRODUCTION: Leishmaniasis is a chronic infectious disease whose spectrum can vary from isolate cutaneous involvement with oligosymptomatic manifestations to systemic involvement with clinically important manifestations. The development of the infection of each type of leishmaniasis (visceral or cutaneous depends on a complex and intriguing interaction between virulence factors of the pathogen and the immune response of the host. Analysis of sera of with Leishmania infection demonstrates the presence of autoantibodies against cellular and humoral components, besides circulating immune complexes and anti-IgG antibodies (rheumatoid factor. Patients with visceral leishmaniasis can present symptoms that mimic Systemic Lupus Erythematosus (SLE, hindering early diagnosis and treatment. OBJECTIVES: To identify the profile of autoantibodies and complement levels of patients with visceral or cutaneous leishmaniasis and to correlate their clinical presentation to those of patients with SLE. METHODS: The presence of autoantibodies and complement levels of 90 patients, 45 with visceral leishmaniasis and 45 with cutaneous leishmaniasis, was determined. Results: The presence of statistically significant autoantibodies in patients with visceral leishmaniasis included: antinuclear antibody (ANA, positive (4.4% or in low titers (8.9%, and IgG anticardiolipin antibody, positive (17.8% or undetermined (8.9%. A reduction in C3 levels was also seen in 17.8% of the patients and anti-Leishmania antibodies > 1/80 in all patients with visceral leishmaniasis. CONCLUSIONS: Visceral leishmaniasis can have a positive correlation with the presence of autoantibodies, possibly by triggering a predominantly humoral, systemic, type Th2 response, representing an obligatory differential diagnosis with SLE, especially in endemic areas.

  19. Casos alóctones de leishmaniose visceral canina no Paraná, Brasil: implicações epidemiológicas Allochthonous cases of canine visceral leishmaniasis in Paraná, Brazil: epidemiological implications

    Vanete Thomaz-Soccol

    2009-09-01

    Full Text Available O presente trabalho teve como objetivo pesquisar a ocorrência de leishmaniose visceral em cães com sinais clínicos compatíveis, procedentes de clínicas veterinárias das diferentes regiões do Estado do Paraná e em caso positivo verificar a autoctonia dos mesmos. Dos animais com suspeita clínica e epidemiológica de LV, foi coletada amostra de sangue para realização de hemograma, provas bioquímicas, sorologia, cultura do parasito, PCR e RAPD. Os cães portadores de quadro clínico, como febre, hiperqueratose, onicogrifose e emagrecimento exagerado, tiveram gânglio poplíteo e/ou medula óssea puncionados e o conteúdo inoculado em meio de cultivo NNN. A extração de DNA do parasito em sangue e cultura foi realizada pelo método fenol/clorofórmio. A amplificação de DNA do protozoário foi feita por PCR e RAPD. Dos 24 animais analisados, o parasito foi isolado em 19 cães. As técnicas moleculares permitiram identificar 14 isolados como L. (Leihmania infantum e cinco como L. (Viannia braziliensis. A análise epidemiológica dos casos permitiu determinar o local de transmissão e definir que todos os cães com LV diagnosticados eram casos alóctones, ou seja eram importados de regiões endêmicas. Sugere-se que a migração dos cães de regiões endêmicas para regiões indenes poderá permitir a instalação de novos focos, desde que o agente encontre ecótopo adequado e vetor específico (Lutzomyia longipalpis.The south region is the only area in Brazil that does not present autochthonous cases of visceral leishmaniasis (VL, however, in the state of Parana, dogs and humans have been found showing a VL compatible clinical profile. In view of this problem, the present work aimed at isolating and identifying the parasite and determining the cases autochthony. All animals clinically suspect of VL were clinically evaluated, and had samples of their blood collected for hemoculture (NNN culture medium, serology, PCR and RAPD-PCR, hemogram

  20. Comparative evaluation of parasitology and serological tests in the diagnosis of visceral leishmaniasis in India: a phase III diagnostic accuracy study.

    Sundar, S; Singh, R K; Bimal, S K; Gidwani, K; Mishra, A; Maurya, R; Singh, S K; Manandhar, K D; Boelaert, M; Rai, M

    2007-02-01

    In this phase III trial for diagnostics for visceral leishmaniasis (VL) in India, we compared parasitological diagnosis with several serological tests: direct agglutination test (freeze dried; DAT-FD), rK-39 strip test, rK-26 strip test and a latex agglutination test for antigen detection in urine (KAtex) in 452 subjects from the endemic regions of Bihar, India. The subjects were segregated into four categories: 230 confirmed patients, 52 probable cases, 70 non-cases and 100 healthy endemic controls. The first two groups were used for estimating sensitivity, the latter two for specificity. Sensitivity of DAT-FD was 98.9%, rK-39: 98.9%, KAtex: 67.0% and rK-26: 21.3%. Sensitivity of DAT-FD on blood taken on filter paper (DAT-FDF) was 99.3%, which was comparable with that using serum. Specificity of serological tests was comparable and high (DAT-FD and DAT-FDF: 94%, rK-39 strip test: 97%, KAtex: 99% and rK-26 strip test: 100%). The classical 'gold standard' parasitological demonstration in splenic smear performed poorly as it missed 18.4% of cases that benefited from VL treatment. Reproducibility of the serological tests between field and central laboratories was excellent (kappa = 1.0, 0.99, 0.96 and 0.94 respectively for microscopy, DAT-FD, rK-39 strip test and rK-26 strip test). A high degree of agreement was observed between DAT-FD and rK-39 strip test (kappa = 0.986). Although DAT-FD and rK-39 strip test were highly sensitive with excellent specificity, the ease of use of the latter makes it most suitable for the diagnosis of VL in the field conditions. PMID:17300637

  1. Antigenicity and protective efficacy of a Leishmania amastigote-specific protein, member of the super-oxygenase family, against visceral leishmaniasis.

    Vivian T Martins

    Full Text Available BACKGROUND: The present study aimed to evaluate a hypothetical Leishmania amastigote-specific protein (LiHyp1, previously identified by an immunoproteomic approach performed in Leishmania infantum, which showed homology to the super-oxygenase gene family, attempting to select a new candidate antigen for specific serodiagnosis, as well as to compose a vaccine against VL. METHODOLOGY/PRINCIPAL FINDINGS: The LiHyp1 DNA sequence was cloned; the recombinant protein (rLiHyp1 was purified and evaluated for its antigenicity and immunogenicity. The rLiHyp1 protein was recognized by antibodies from sera of asymptomatic and symptomatic animals with canine visceral leishmaniasis (CVL, but presented no cross-reactivity with sera of dogs vaccinated with Leish-Tec, a Brazilian commercial vaccine; with Chagas' disease or healthy animals. In addition, the immunogenicity and protective efficacy of rLiHyp1 plus saponin was evaluated in BALB/c mice challenged subcutaneously with virulent L. infantum promastigotes. rLiHyp1 plus saponin vaccinated mice showed a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with the recombinant protein. Immunized and infected mice, as compared to the control groups (saline and saponin, showed significant reductions in the number of parasites found in the liver, spleen, bone marrow, and in the paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, produced mainly by CD4 T cells. In these mice, a decrease in the parasite-mediated IL-4 and IL-10 response could also be observed. CONCLUSIONS/SIGNIFICANCE: The present study showed that this Leishmania oxygenase amastigote-specific protein can be used for a more sensitive and specific serodiagnosis of asymptomatic and symptomatic CVL and, when combined with a Th1-type adjuvant, can also be employ as a candidate antigen to develop vaccines against VL.

  2. Strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in India and Nepal.

    Epco Hasker

    Full Text Available INTRODUCTION: Asymptomatic persons infected with the parasites causing visceral leishmaniasis (VL usually outnumber clinically apparent cases by a ratio of 4-10 to 1. We assessed the risk of progression from infection to disease as a function of DAT and rK39 serological titers. METHODS: We used available data on four cohorts from villages in India and Nepal that are highly endemic for Leishmania donovani. In each cohort two serosurveys had been conducted. Based on results of initial surveys, subjects were classified as seronegative, moderately seropositive or strongly seropositive using both DAT and rK39. Based on the combination of first and second survey results we identified seroconvertors for both markers. Seroconvertors were subdivided in high and low titer convertors. Subjects were followed up for at least one year following the second survey. Incident VL cases were recorded and verified. RESULTS: We assessed a total of 32,529 enrolled subjects, for a total follow-up time of 72,169 person years. Altogether 235 incident VL cases were documented. The probability of progression to disease was strongly associated with initial serostatus and with seroconversion; this was particularly the case for those with high titers and most prominently among seroconvertors. For high titer DAT convertors the hazard ratio reached as high as 97.4 when compared to non-convertors. The strengths of the associations varied between cohorts and between markers but similar trends were observed between the four cohorts and the two markers. DISCUSSION: There is a strongly increased risk of progressing to disease among DAT and/or rK39 seropositives with high titers. The options for prophylactic treatment for this group merit further investigation, as it could be of clinical benefit if it prevents progression to disease. Prophylactic treatment might also have a public health benefit if it can be corroborated that these asymptomatically infected individuals are infectious

  3. Higher Expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 Chemokines in the Skin Associated with Parasite Density in Canine Visceral Leishmaniasis

    Menezes-Souza, Daniel; Guerra-Sá, Renata; Carneiro, Cláudia Martins; Vitoriano-Souza, Juliana; Giunchetti, Rodolfo Cordeiro; Teixeira-Carvalho, Andréa; Silveira-Lemos, Denise; Oliveira, Guilherme Corrêa; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

    2012-01-01

    Background The immune response in the skin of dogs infected with Leishmania infantum is poorly understood, and limited studies have described the immunopathological profile with regard to distinct levels of tissue parasitism and the clinical progression of canine visceral leishmaniasis (CVL). Methodology/Principal Findings A detailed analysis of inflammatory cells (neutrophils, eosinophils, mast cells, lymphocytes, and macrophages) as well as the expression of chemokines (CCL2, CCL4, CCL5, CCL13, CCL17, CCL21, CCL24, and CXCL8) was carried out in dermis skin samples from 35 dogs that were naturally infected with L. infantum. The analysis was based on real-time polymerase chain reaction (PCR) in the context of skin parasitism and the clinical status of CVL. We demonstrated increased inflammatory infiltrate composed mainly of mononuclear cells in the skin of animals with severe forms of CVL and high parasite density. Analysis of the inflammatory cell profile of the skin revealed an increase in the number of macrophages and reductions in lymphocytes, eosinophils, and mast cells that correlated with clinical progression of the disease. Additionally, enhanced parasite density was correlated with an increase in macrophages and decreases in eosinophils and mast cells. The chemokine mRNA expression demonstrated that enhanced parasite density was positively correlated with the expression of CCL2, CCL4, CCL5, CCL21, and CXCL8. In contrast, there was a negative correlation between parasite density and CCL24 expression. Conclusions/Significance These findings represent an advance in the knowledge about skin inflammatory infiltrates in CVL and the systemic consequences. Additionally, the findings may contribute to the design of new and more efficient prophylactic tools and immunological therapies against CVL. PMID:22506080

  4. Diagnosis of canine visceral leishmaniasis with radiolabelled probes: comparison of the kDNA PCR-hybridization with three molecular methods in different clinical samples

    Leishmania (Leishmania) chagasi is responsible for visceral leishmaniasis (VL) in Brazil and the dog is the main domestic reservoir. Disease control is based on the elimination of infected animals and the use of a sensitive and specific diagnostic test is necessary. The Brazilian VL control program emphasizes serologic surveys, mainly using the enzyme-linked immunosorbent assay (ELISA) and the immunofluorescence antibody test (IFAT), followed by the elimination of the seropositive dogs. However, these techniques present limitations in terms of sensitivity and specificity. The Polymerase Chain Reaction (PCR) associated to hybridization with DNA probes labeled with 32P has been recognized as a valuable tool for Leishmania identification. In this study, the sensitivity of kDNA PCR hybridization method was compared with three other molecular methods: Internal Transcribed Spacer 1 Nested PCR (ITS-1nPCR), Leishmania nested PCR (LnPCR) and Seminested kDNA PCR (kDNA snPCR). The comparison was performed in different clinical specimens: conjunctival swab, skin, blood and bone marrow. A group of thirty symptomatic dogs, positive in the parasitological and serological tests, was used. When. The techniques targeting kDNA mini-circles (kDNA snPCR and KDNA PCR-hybridization) showed the worst result for blood samples. The KDNA-PCR hybridization showed the best sensitivity for conjunctival swab. By comparing the samples on the basis of positivity obtained by the sum of all methods, the blood showed the worst outcome (71/120).The bone marrow showed the highest positivity (106/120), followed by conjunctival swab (100/120) and skin (89/120). Since the bone marrow samples are unsuitable for routine epidemiological surveys, the conjunctival swab was recommended because it allows high sensitivity, especially when associated with kDNA PCR hybridization method, and is a noninvasive sampling method. (author)

  5. Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial.

    Eltahir A G Khalil

    Full Text Available BACKGROUND: Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL but the appropriate single dose is unknown. METHODOLOGY: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT PCR. PRINCIPAL FINDINGS: The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73-93%, 40% (95%CI 19-64%, and 58% (95%CI 41-73% in patients treated with multiple doses (n = 63, and single doses of 7·5 (n = 21 or 10 mg/kg (n = 40, respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. CONCLUSIONS: The tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. TRIALS REGISTRATION: www.clinicaltrials.govNCT00832208.

  6. Temporal, spatial and spatiotemporal analysis of the occurrence of visceral leishmaniasis in humans in the City of Birigui, State of São Paulo, from 1999 to 2012

    Carolina Portugal Vieira

    2014-06-01

    Full Text Available Introduction In 1999, Birigui and Araçatuba were the first municipalities in the State of São Paulo to present autochthonous cases of visceral leishmaniasis in humans (VLH. The aim of this study was to describe the temporal, spatial and spatiotemporal behaviors of VLH in Birigui. Methods Secondary data were obtained from the Notifiable Diseases Information System from 1999 to 2012. The incidence, mortality and case fatality rates by sex and age were calculated. The cases of VLH were geocoded and grouped according to census tracts. Local empirical Bayesian incidence rates were calculated. The existence of spatial and spatiotemporal clusters was investigated using SaTScan software. Results There were 156 confirmed cases of autochthonous VLH. The incidence rate was higher in the 0-4-year-old children, and the mortality and case fatality rates were higher in people aged 60 years and older. The peaks of incidence occurred in 2006 and 2011. The Bayesian rates identified the presence of VLH in all of the census tracts in the municipality; however, spatial and spatiotemporal clusters were found in the central area of the municipality. Conclusions Birigui, located in the Araçatuba region, has recently experienced increasing numbers of VLH cases; this increase is contrary to the behavior observed over the entire region, which has shown a decreasing trend in the number of VLH cases. The observations that the highest incidence is in children 0-4 years old and the highest mortality is in people 60 years and older are in agreement with the expected patterns of VLH.

  7. Diagnosis of canine visceral leishmaniasis with radiolabelled probes: comparison of the kDNA PCR-hybridization with three molecular methods in different clinical samples

    Ferreira, Aline Leandra C.; Ferreira, Sidney A.; Carregal, Virginia M.; Andrade, Antero Silva R., E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Lab. de Radiobiologia; Melo, Maria N., E-mail: melo@icb.ufmg.br [Departamento de Parasitologia. Instituto de Ciencias Biologicas. Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2011-07-01

    Leishmania (Leishmania) chagasi is responsible for visceral leishmaniasis (VL) in Brazil and the dog is the main domestic reservoir. Disease control is based on the elimination of infected animals and the use of a sensitive and specific diagnostic test is necessary. The Brazilian VL control program emphasizes serologic surveys, mainly using the enzyme-linked immunosorbent assay (ELISA) and the immunofluorescence antibody test (IFAT), followed by the elimination of the seropositive dogs. However, these techniques present limitations in terms of sensitivity and specificity. The Polymerase Chain Reaction (PCR) associated to hybridization with DNA probes labeled with {sup 32}P has been recognized as a valuable tool for Leishmania identification. In this study, the sensitivity of kDNA PCR hybridization method was compared with three other molecular methods: Internal Transcribed Spacer 1 Nested PCR (ITS-1nPCR), Leishmania nested PCR (LnPCR) and Seminested kDNA PCR (kDNA snPCR). The comparison was performed in different clinical specimens: conjunctival swab, skin, blood and bone marrow. A group of thirty symptomatic dogs, positive in the parasitological and serological tests, was used. When. The techniques targeting kDNA mini-circles (kDNA snPCR and KDNA PCR-hybridization) showed the worst result for blood samples. The KDNA-PCR hybridization showed the best sensitivity for conjunctival swab. By comparing the samples on the basis of positivity obtained by the sum of all methods, the blood showed the worst outcome (71/120).The bone marrow showed the highest positivity (106/120), followed by conjunctival swab (100/120) and skin (89/120). Since the bone marrow samples are unsuitable for routine epidemiological surveys, the conjunctival swab was recommended because it allows high sensitivity, especially when associated with kDNA PCR hybridization method, and is a noninvasive sampling method. (author)

  8. Human immunodeficiency virus/Leishmania infantum in the first foci of urban American visceral leishmaniasis: clinical presentation from 1994 to 2010

    Iúri Paz Lima

    2013-04-01

    Full Text Available INTRODUCTION: Human immunodeficiency virus (HIV coinfection with Leishmania infantum or Leishmania donovani, the agents of visceral leishmaniasis (or kala-azar, has become a fatal public health problem in the tropics where kala-azar is endemic. METHODS: The clinical presentation of patients with HIV and L. infantum coinfection is described using two unique databases that together produce the largest case series of patients with kala-azar infected with HIV in South America. First, a retrospective study paired the list of all patients with kala-azar from 1994 to 2004 with another of all patients with HIV/AIDS from the reference hospital for both diseases in the City of Teresina, State of Piauí, Brazil. Beginning in 2005 through to 2010 this information was prospectively collected at the moment of hospitalization. RESULTS: During the study, 256 admissions related to 224 patients with HIV/L. infantum coinfection were registered and most of them were males between 20-40 years of age. Most of the 224 patients were males between 20-40 years of age. HIV contraction was principally sexual. The most common symptoms and signs were pallor, fever, asthenia and hepatosplenomegaly. 16.8% of the cohort died. The primary risk factors associated to death were kidney or respiratory failure, somnolence, hemorrhagic manifestations and a syndrome of systemic inflammation. The diagnosis of HIV and kala-azar was made simultaneously in 124 patients. CONCLUSIONS: The urban association between HIV and kala-azar coinfection in South America is worrisome due to difficulty in establishing the diagnosis and higher mortality among the coinfected then those with either disease independently. HIV/L. infantum coinfection exhibits some singular characteristics and due to its higher mortality it requires immediate assistance to patients and greater research on appropriate combination therapy.

  9. Human immunodeficiency virus/Leishmania infantum in the first foci of urban American visceral leishmaniasis: clinical presentation from 1994 to 2010

    Iúri Paz Lima

    2013-09-01

    Full Text Available INTRODUCTION: Human immunodeficiency virus (HIV coinfection with Leishmania infantum or Leishmania donovani, the agents of visceral leishmaniasis (or kala-azar, has become a fatal public health problem in the tropics where kala-azar is endemic. METHODS: The clinical presentation of patients with HIV and L. infantum coinfection is described using two unique databases that together produce the largest case series of patients with kala-azar infected with HIV in South America. First, a retrospective study paired the list of all patients with kala-azar from 1994 to 2004 with another of all patients with HIV/AIDS from the reference hospital for both diseases in the City of Teresina, State of Piauí, Brazil. Beginning in 2005 through to 2010 this information was prospectively collected at the moment of hospitalization. RESULTS: During the study, 256 admissions related to 224 patients with HIV/L. infantum coinfection were registered and most of them were males between 20-40 years of age. Most of the 224 patients were males between 20-40 years of age. HIV contraction was principally sexual. The most common symptoms and signs were pallor, fever, asthenia and hepatosplenomegaly. 16.8% of the cohort died. The primary risk factors associated to death were kidney or respiratory failure, somnolence, hemorrhagic manifestations and a syndrome of systemic inflammation. The diagnosis of HIV and kala-azar was made simultaneously in 124 patients. CONCLUSIONS: The urban association between HIV and kala-azar coinfection in South America is worrisome due to difficulty in establishing the diagnosis and higher mortality among the coinfected then those with either disease independently. HIV/L. infantum coinfection exhibits some singular characteristics and due to its higher mortality it requires immediate assistance to patients and greater research on appropriate combination therapy.

  10. Abundance of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae and urban transmission of visceral leishmaniasis in Campo Grande, state of Mato Grosso do Sul, Brazil

    Alessandra Gutierrez de Oliveira

    2006-12-01

    Full Text Available The outspread and urbanization of visceral leishmaniasis (VL in Campo Grande, state of Mato Grosso do Sul, lead us to undertake the present study over diversity and abundance of sand flies in the urban area to compare with previous search carried out during 1999/2000, before the identification of the disease in the human population.The captures were carried out with automatic light traps, weekly, from February 2004 to February 2005 on three sites including a forested area (Zé Pereira, two peridomicilies (shelters of domestic animals and cultivation areas, and intradomicilie. In the present study 110 collections were obtained during 13 months for 1320 h of collections, resulting in 5004 specimens, 3649 males and 1355 females belonging to the 20 following species: Brumptomyia avellari, Brumptomyia sp., Bichromomyia flaviscutellata, Evandromyia lenti, E. termitophila, E. cortelezzii, E. borrouli, Lutzomyia sp., L. longipalpis, Micropygomyia quinquefer, N. antunesi, N. whitmani, Pintomyia christenseni, Pi. damascenoi, Psathyromyia aragaoi, Ps. campograndensis, Ps. hermanlenti, Ps. shannoni, Pychodopygus claustrei, and Sciopemyia sordellii. L. longipalpis was the most abundant species in the anthropic environment with 92.22% of the captures. This shows an increase of sixty times in the density of L. longipalpis compared to the last sand fly evaluation in 1999/2000. The high density of L. longipalpis in Campo Grande is the main factor of risk in transmission of the disease to human in the urban area. The capture of N. antunesi, typical specie from Amazonian region, in Mato Grosso do Sul is reported for the first time.

  11. Therapy with radio-attenuated vaccine in experimental murine visceral leishmaniasis showed enhanced T cell and inducible nitric oxide synthase levels, suppressed tumor growth factor-beta production with higher expression of some signaling molecules

    Sanchita Datta; Syamal Roy; Madhumita Manna

    2015-01-01

    Background:Visceral leishmaniasis (VL) or Kala-Azar (KA) is one of the most deadly forms of disease among all neglected tropical diseases. There are no satisfactory drugs or vaccine candidates available for this dreaded disease. Our previous studies showed promising therapeutic and prophylactic efficacy of the live, radio-attenuated parasites through intramuscular (I.M.) and intraperitoneal (I.P.) route in BALB/c mice model.Methods:The T-cell proliferation level, the mRNA expression level of ...

  12. Dichotomy of the human T cell response to Leishmania antigens. II. Absent or Th2-like response to gp63 and Th1-like response to lipophosphoglycan-associated protein in cells from cured visceral leishmaniasis patients

    Kurtzhals, J A; Hey, A S; Jardim, A;

    1994-01-01

    The T cell response to different Leishmania donovani antigens was investigated using peripheral blood mononuclear cells (PBMC) from Kenyans cured of visceral leishmaniasis and non-exposed Danes. Crude promastigote and amastigote antigens both induced proliferation and interferon-gamma (IFN......-gamma) production in PBMC from cured patients, while cells from non-exposed donors gave weak responses. A similar pattern was induced by lipophosphoglycan-associated protein (LPGAP). By contrast, the major surface protease of Leishmania, gp63, induced only a weak proliferative response without IFN-gamma production...

  13. Asymptomatic infection in family contacts of patients with human visceral leishmaniasis in Três Lagoas, Mato Grosso do Sul State, Brazil Infecção assintomática em contactantes de pacientes com leishmaniose visceral humana em Três Lagoas, Mato Grosso do Sul, Brasil

    Ana Lúcia Lyrio de Oliveira

    2008-12-01

    Full Text Available The Brazilian city of Três Lagoas, Mato Grosso do Sul State, has experienced an urban outbreak of visceral leishmaniasis since 2000. In 2002, due to the increase in the number of cases, 46 families with cases of visceral leishmaniasis were studied to verify the prevalence of asymptomatic infection in household contacts. Indirect immunofluorescence and ELISA showed a 36.4% positive infection rate. There were no cases of symptomatic disease among these contacts. There was no statistically significant difference in gender or age. Median age was 21 years, and the 10-19-year age bracket was the most heavily affected (23%. As for family characteristics, no differences were observed in schooling or family income; most families (58.7% owned their homes, which were built of masonry (97.8% and had adequate infrastructure. All the families reported what were probably phlebotomine sand flies in the peridomicile. In conclusion, asymptomatic visceral leishmaniasis infection is frequent and occurs in both males and females, regardless of age.O Município de Três Lagoas, Mato Grosso do Sul, Brasil, foi alvo de uma epidemia de leishmaniose visceral a partir de 2000. Em 2002, devido ao incremento de casos, estudou-se 46 famílias que apresentavam um caso de doença para verificar-se o percentual de positividade de infecção assintomática por leishmaniose visceral em contactantes. Encontrou-se 36,4% de positividade pelos testes sorológicos Reação de Imunofluorescência Indireta e/ou imunoenzimático ELISA, sem diferença estatisticamente significativa quanto ao sexo e faixa etária. A mediana de idade foi de 21 anos, sendo a faixa etária mais acometida de 10 a 19 anos (23%. Quanto às características familiares não observaram-se diferenças quanto ao nível de instrução e renda familiar; a moradia, em sua maioria, era própria (58,7%, em alvenaria (97,8%, com infra-estrutura adequada. Todas as famílias relataram a presença de provável flebotom

  14. Localised Leishmaniasis of Oral Mucosa: Report of an Unusual Clinicopathological Entity

    Deepak Passi; Sarang Sharma; Shubharanjan Dutta; Chandan Gupta

    2014-01-01

    The term leishmaniasis comprises of a group of diseases caused by different species of a protozoan called Leishmania. There are three main clinical forms of leishmaniasis: visceral leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis. Exclusive involvement of the mucosa is very rare. We present a case of mucosal leishmaniasis located in the oral cavity. The only manifestation of leishmaniasis disease in the described case was the appearance of an oral lesion. Treatment was ...

  15. Sandflies (Psychodidae: Phlebotominae survey in an urban transmission area of visceral leishmaniasis, Northeastern Brazil Pesquisa de flebotomíneos (Psychodidae: Phlebotominae em área urbana de transmissão de leishmaniose visceral no Nordeste do Brasil

    Sthenia Santos Albano Amóra

    2010-12-01

    Full Text Available Visceral leishmaniasis (VL is a major public health challenge in Brazil, especially in states where it is endemic. The aim of this study was to investigate the relationship of sand fly population density with environmental variables (temperature, rainfall and relative humidity in urban areas of the city of Mossoró, Rio Grande do Norte, Northeastern Brazil. Sand flies were captured with Center Disease Control (CDC traps installed monthly in the intra and peridomicile of three houses. Data analysis was based on the chi-square test and linear regression. A total of 7,347 sand flies were captured, being 93.85% Lutzomyia longipalpis and 6.15% Lutzomyia evandroi. Sand flies were more commonly found in the peridomicile and there was no difference between the number of males and females. The variables rainy season as well as relative humidity and rainfall, alone or together, did not have an effect on sand fly population density. However, high temperatures had a negative effect. The study of the behavior of sand flies in specific units of endemic areas can provide input to public health authorities for planning appropriate VL vector control measures.A leishmaniose visceral (LV é um grande desafio para a saúde pública no Brasil, particularmente nos estados onde é endêmica. O objetivo deste estudo foi verificar a relação da densidade populacional de flebotomíneos com as variáveis ambientais (temperatura, precipitação de chuva e umidade relativa do ar em bairros urbanos de Mossoró, Rio Grande do Norte. Os flebotomíneos foram capturados com armadilhas CDC instaladas mensalmente no intra e peridomicílio de três casas. A análise dos dados foi baseada no teste Qui-quadrado e na regressão linear. Foram capturados 7.347 flebotomíneos, sendo 93,85% Lutzomyia longipalpis e 6,15% Lutzomyia evandroi. Os flebotomíneos foram encontrados mais comumente no peridomicílio e nenhuma diferença significativa entre o número de machos e fêmeas foi

  16. Visceral leishmaniasis in heart transplant patients in the endemic state of Ceará, Brazil: a report of two casesLeishmaniose visceral em pacientes submetidos a transplante cardíaco no estado do Ceará, área endêmica no Brasil: um relato de dois casos

    Bráulio Matias de Carvalho

    2016-03-01

    Full Text Available Visceral leishmaniasis (VL in transplant patients is a serious disease, with atypical and aggressive manifestations, compromising patient survival. During the period from 2008 to 2012, 126 heart transplants were performed in the state of Ceará, Brazil, of which, two patients developed VL. Fever, pancytopenia and hepatosplenomegaly were the common clinical signs. Both patients were diagnosed and properly treated, but the first one had a clinical relapse and died, five months after treatment. These findings emphasize the importance of investigating VL in heart-transplant patients in endemic areas and highlight the importance of early diagnosis and treatment for favorable clinical outcomes.

  17. Association of environmental and climatic factors in the epidemiology of American visceral leishmaniasis in northeast Brazil using remote sensing and geographical information system methods

    Thompson, Roland Alexander

    This study associated climatic and environmental factors with the incidence of visceral leishmaniasis (calazar) in Northeast Brazil. Remote sensing (RS) techniques permitted evaluation of spatial and temporal landscape features to stratify the region and define the target population for this vector-borne disease. The Municipality of Caninde, Ceara, Brazil was divided into 873-- 2 x 2 km2 squares centered on coordinates from a Universal Transverse Mercator projection (scale 1:100,000, 1994) and geo-referenced with 2 Landsat T.M. (TM) scenes (September 26, 1976 and July 2, 1996). The assignment of squares into foothills, plains or city strata was based on vegetative categories determined from TM scenes (Bands: 4,5,3) with ERDAS Imagine ISODATA classification procedures. Odds Ratios (OR) with 95% Confidence Intervals (CI) were determined for the juveniles less than age 10 based on 17 years of demographic, calazar incidence and rainfall information supplied by: Fundacao Nacional de Saude, Fundacao Cearense do Metorologia e Recurso Hidricos, and Fundacao Instituto de Planejamento do Ceara. The population and number of calazar cases were determined for each 2 x 2 km 2 square. The odds ratio of calazar for a Caninde juvenile in the foothills relative to the city was OR = 4.11 CI (3.2, 5.3). The calazar odds ratio for juveniles living in years with 3-year rainfall average between 60--90 cm was OR = 3.07 CI (1.3, 7.2), the rainfall average between 40--60 cm had OR = 9.12 CI (4.4, 23.3), and with less than 40 cm OR = 9.23 CI (3.9, 25.2) relative to years with an average greater than 90 cm. The logistic regression model for Ceara comprised an ordinal-incidence-density-response variable, a 5-level region explanatory variable, and a 3-level juvenile proportion variable. The odds ratios for calazar in municipalities located in the interior high plains was OR = 1.94 CI (1.6, 2.4) relative to location in the littoral and for a municipality with less than 26% juvenile population

  18. Chemical and environmental vector control as a contribution to the elimination of visceral leishmaniasis on the Indian subcontinent: cluster randomized controlled trials in Bangladesh, India and Nepal

    Das Pradeep

    2009-10-01

    Full Text Available Abstract Background Bangladesh, India and Nepal are working towards the elimination of visceral leishmaniasis (VL by 2015. In 2005 the World Health Organization/Training in Tropical Diseases launched an implementation research programme to support integrated vector management for the elimination of VL from Bangladesh, India and Nepal. The programme is conducted in different phases, from proof-of-concept to scaling up intervention. This study was designed in order to evaluate the efficacy of the three different interventions for VL vector management: indoor residual spraying (IRS; long-lasting insecticide treated nets (LLIN; and environmental modification (EVM through plastering of walls with lime or mud. Methods Using a cluster randomized controlled trial we compared three vector control interventions with a control arm in 96 clusters (hamlets or neighbourhoods in each of the 4 study sites: Bangladesh (one, India (one and Nepal (two. In each site four villages with high reported VL incidences were included. In each village six clusters and in each cluster five households were randomly selected for sand fly collection on two consecutive nights. Control and intervention clusters were matched with average pre-intervention vector densities. In each site six clusters were randomly assigned to each of the following interventions: indoor residual spraying (IRS; long-lasting insecticide treated nets (LLIN; environmental management (EVM or control. All the houses (50-100 in each intervention cluster underwent the intervention measures. A reduction of intra-domestic sand fly densities measured in the study households by overnight US Centres for Disease Prevention and Control light trap captures (that is the number of sand flies per trap per night was the main outcome measure. Results IRS, and to a lesser extent EVM and LLINs, significantly reduced sand fly densities for at least 5 months in the study households irrespective of type of walls or whether or

  19. Diagnostic accuracy of loop-mediated isothermal amplification (LAMP for detection of Leishmania DNA in buffy coat from visceral leishmaniasis patients

    Khan Md Gulam Musawwir

    2012-12-01

    Full Text Available Abstract Background Visceral leishmaniasis (VL remains as one of the most neglected tropical diseases with over 60% of the world’s total VL cases occurring in the Indian subcontinent. Due to the invasive risky procedure and technical expertise required in the classical parasitological diagnosis, the goal of the VL experts has been to develop noninvasive procedure(s applicable in the field settings. Several serological and molecular biological approaches have been developed over the last decades, but only a few are applicable in field settings that can be performed with relative ease. Recently, loop-mediated isothermal amplification (LAMP has emerged as a novel nucleic acid amplification method for diagnosis of VL. In this study, we have evaluated the LAMP assay using buffy coat DNA samples from VL patients in Bangladesh and compared its performance with leishmania nested PCR (Ln-PCR, an established molecular method with very high diagnostic indices. Methods Seventy five (75 parasitologically confirmed VL patients by spleen smear microcopy and 101 controls (endemic healthy controls −25, non-endemic healthy control-26, Tuberculosis-25 and other diseases-25 were enrolled in this study. LAMP assay was carried out using a set of four primers targeting L. donovani kinetoplast minicircle DNA under isothermal (62 °C conditions in a heat block. For Ln-PCR, we used primers targeting the parasite’s small-subunit rRNA region. Results LAMP assay was found to be positive in 68 of 75 confirmed VL cases, and revealed its diagnostic sensitivity of 90.7% (95.84-81.14, 95% CI, whereas all controls were negative by LAMP assay, indicating a specificity of 100% (100–95.43, 95% CI. The Ln-PCR yielded a sensitivity of 96% (98.96-87.97, 95% CI and a specificity of 100% (100–95.43, 95% CI. Conclusion High diagnostic sensitivity and excellent specificity were observed in this first report of LAMP diagnostic evaluation from Bangladesh. Considering its many fold

  20. Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome® for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial

    Khalil, Eltahir A. G.; Weldegebreal, Teklu; Younis, Brima M.; Omollo, Raymond; Musa, Ahmed M.; Hailu, Workagegnehu; Abuzaid, Abuzaid A.; Dorlo, Thomas P. C.; Hurissa, Zewdu; Yifru, Sisay; Haleke, William; Smith, Peter G.; Ellis, Sally; Balasegaram, Manica; EL-Hassan, Ahmed M.; Schoone, Gerard J.; Wasunna, Monique; Kimutai, Robert; Edwards, Tansy; Hailu, Asrat

    2014-01-01

    Background Anti-leishmanial drug regimens that include a single dose AmBisome® could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. Methodology A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome® for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome® 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1–5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR. Principal Findings The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73–93%), 40% (95%CI 19–64%), and 58% (95%CI 41–73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. Conclusions The tested AmBisome® regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. Trials Registration www.clinicaltrials.gov NCT00832208 PMID:24454970

  1. Risk Zone Modelling and Early Warning System for Visceral Leishmaniasis Kala-Azar Disease in Bihar, India Using Remote Sensing and GIS

    Jeyaram, A.; Kesari, S.; Bajpai, A.; Bhunia, G. S.; Krishna Murthy, Y. V. N.

    2012-07-01

    Visceral Leishmaniasis (VL) commonly known as Kala-azar is one of the most neglected tropical disease affecting approximately 200 million poorest populations 'at risk in 109 districts of three endemic countries namely Bangladesh, India and Nepal at different levels. This tropical disease is caused by the protozoan parasite Leishmania donovani and transmitted by female Phlebotomus argentipes sand flies. The analysis of disease dynamics indicate the periodicity at seasonal and inter-annual temporal scale which forms the basis for development of advanced early warning system. Study area of highly endemic Vaishali district, Bihar, India has been taken for model development. A Systematic study of geo-environmental parameters derived from satellite data in conjunction with ground intelligence enabled modelling of infectious disease and risk villages. High resolution Indian satellites data of IRS LISS IV (multi-spectral) and Cartosat-1 (Pan) have been used for studying environmentally risk parameters viz. peri-domestic vegetation, dwelling condition, wetland ecosystem, cropping pattern, Normalised Difference Vegetation Index (NDVI), detailed land use etc towards risk assessment. Univariate analysis of the relationship between vector density and various land cover categories and climatic variables suggested that all the variables are significantly correlated. Using the significantly correlated variables with vector density, a seasonal multivariate regression model has been carried out incorporating geo-environmental parameters, climate variables and seasonal time series disease parameters. Linear and non-linear models have been applied for periodicity and interannual temporal scale to predict Man-hour-density (MHD) and 'out-of-fit' data set used for validating the model with reasonable accuracy. To improve the MHD predictive approach, fuzzy model has also been incorporated in GIS environment combining spatial geo-environmental and climatic variables using fuzzy membership

  2. Canine Leishmaniasis, Italy

    Ferroglio, Ezio; Maroli, Michele; Gastaldo, Silvia; Mignone, Walter; Rossi, Luca

    2005-01-01

    We report the results of a survey to determine the prevalence of canine leishmaniasis and the presence of sand flies in northwestern Italy, where autochthonous foci of canine leishmaniasis have not been reported. Active foci of canine leishmaniasis were identified, which suggests that the disease is now also endemic in continental climate areas.

  3. Constitutive adipocyte mTORC1 activation enhances mitochondrial activity and reduces visceral adiposity in mice.

    Magdalon, Juliana; Chimin, Patricia; Belchior, Thiago; Neves, Rodrigo X; Vieira-Lara, Marcel A; Andrade, Maynara L; Farias, Talita S; Bolsoni-Lopes, Andressa; Paschoal, Vivian A; Yamashita, Alex S; Kowaltowski, Alicia J; Festuccia, William T

    2016-05-01

    Mechanistic target of rapamycin complex 1 (mTORC1) loss of function reduces adiposity whereas partial mTORC1 inhibition enhances fat deposition. Herein we evaluated how constitutive mTORC1 activation in adipocytes modulates adiposity in vivo. Mice with constitutive mTORC1 activation in adipocytes induced by tuberous sclerosis complex (Tsc)1 deletion and littermate controls were evaluated for body mass, energy expenditure, glucose and fatty acid metabolism, mitochondrial function, mRNA and protein contents. Adipocyte-specific Tsc1 deletion reduced visceral, but not subcutaneous, fat mass, as well as adipocyte number and diameter, phenotypes that were associated with increased lipolysis, UCP-1 content (browning) and mRNA levels of pro-browning transcriptional factors C/EBPβ and ERRα. Adipocyte Tsc1 deletion enhanced mitochondrial oxidative activity, fatty acid oxidation and the expression of PGC-1α and PPARα in both visceral and subcutaneous fat. In brown adipocytes, however, Tsc1 deletion did not affect UCP-1 content and basal respiration. Adipocyte Tsc1 deletion also reduced visceral adiposity and enhanced glucose tolerance, liver and muscle insulin signaling and adiponectin secretion in mice fed with purified low- or high-fat diet. In conclusion, adipocyte-specific Tsc1 deletion enhances mitochondrial activity, induces browning and reduces visceral adiposity in mice. PMID:26923434

  4. The sesquiterpene (-)-α-bisabolol is active against the causative agents of Old World cutaneous leishmaniasis through the induction of mitochondrial-dependent apoptosis.

    Corpas-López, V; Merino-Espinosa, G; Díaz-Sáez, V; Morillas-Márquez, F; Navarro-Moll, M C; Martín-Sánchez, J

    2016-10-01

    Cutaneous leishmaniasis treatment remains challenging due to the absence of a satisfactory treatment. The screening of natural compounds is a valuable strategy in the search of new drugs against leishmaniasis. The sesquiterpene (-)-α-bisabolol is effective in vivo against visceral leishmaniasis due to Leishmania infantum, but its mechanism of action remains elusive. The aim of this study is to validate this promising compound against the causative species of Old World cutaneous leishmaniasis and to get an insight into its antileishmanial mode of action. The compound was evaluated on L. tropica promastigotes and intracellular amastigotes using bone marrow-derived macrophages and its cytotoxicity was evaluated on L929 fibroblasts. The reactive oxygen species generation was evaluated using a sensitive probe. Mitochondrial depolarization was assessed evaluating the fluorescence due to rhodamine 123 in a flow cytometer. Apoptosis was investigated by measuring the fluorescence due to annexin V and propidium iodide in a flow cytometer. The ultrastructure of treated promastigotes and intracellular amastigotes was analysed through transmission electron microscopy. (-)-α-Bisabolol was active against L. tropica intracellular amastigotes displaying an inhibitory concentration 50 % of 25.2 µM and showing low cytotoxicity. This compound induced time and dose-dependent oxidative stress, mitochondrial depolarization and phosphatidilserine externalization (a marker of apoptosis). These effects were noticed at a low concentration and short exposure time. In the ultrastructural analyses, the treated parasites showed mitochondrial disruption, presence of electron-dense structures and chromatin condensation. These results suggest that this natural compound induces oxidative stress and mitochondrial-dependent apoptosis on Leishmania without disturbing the plasma membrane. PMID:27539477

  5. Co-administration of glycyrrhizic acid with the antileishmanial drug sodium antimony gluconate (SAG) cures SAG-resistant visceral leishmaniasis.

    Bhattacharjee, Amrita; Majumder, Saikat; Majumdar, Suchandra Bhattacharyya; Choudhuri, Soumitra Kumar; Roy, Syamal; Majumdar, Subrata

    2015-03-01

    Since there are very few affordable antileishmanial drugs available, antimonial resistance has crippled antileishmanial therapy, thereby emphasising the need for development of novel therapeutic strategies. This study aimed to evaluate the antileishmanial role of combined therapy with sodium antimony gluconate (SAG) and the triterpenoid glycyrrhizic acid (GA) against infection with SAG-resistant Leishmania (GE1F8R). Combination therapy with GA and SAG successfully limited infection with SAG-resistant Leishmania in a synergistic manner (fractional inhibitory concentration index resistant Leishmania and co-treated with GA and SAG exhibited a significant reduction in hepatic and splenic parasite burden. In probing the mechanism, it was observed that GA treatment suppressed the expression and efflux activity of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1), two host ABC transporters responsible for antimony efflux from host cells infected with SAG-resistant parasites. This suppression correlated with greater intracellular antimony retention during SAG therapy both in vitro and in vivo, which was reflected in the reduced parasite load. Furthermore, co-administration of GA and SAG induced a shift in the cytokine balance towards a Th1 phenotype by augmenting pro-inflammatory cytokines (such as IL-12, IFNγ and TNFα) and inducing nitric oxide generation in GE1F8R-infected macrophages as well as GE1F8R-infected mice. This study aims to provide an affordable leishmanicidal alternative to expensive antileishmanial drugs such as miltefosine and amphotericin B. Furthermore, this report explores the role of GA as a resistance modulator in MRP1- and P-gp-overexpressing conditions. PMID:25600891

  6. Protective effect of Croton caudatus Geisel leaf extract against experimental visceral leishmaniasis induces proinflammatory cytokines in vitro and in vivo.

    Dey, Somaditya; Mukherjee, Debarati; Chakraborty, Sondipon; Mallick, Suvadip; Dutta, Aritri; Ghosh, Joydip; Swapana, Ningombam; Maiti, Swatilekha; Ghorai, Narayan; Singh, Chingakham Brajakishor; Pal, Chiranjib

    2015-01-01

    In the present state of overwhelming emergence of drug-unresponsive phenotypes of Leishmania donovani and persistent severe toxicity in conventional anti-leishmanial therapy, in search for novel leads, the aim of this study has been fixed to identify the active extract(s) of Croton caudatus Geisel. var. tomentosus Hook effective against the parasitic protozoans in vitro and in vivo. C. caudatus Geisel. is often used by Chakma and Hmar community, the local tribes of north-east India for medicinal and veterinary purposes. Among the five semi-purified extracts tested, C. caudatus leaves, extracted in hexane and subsequently semi-purified in a column packed with silica gel (70-130 µM; mesh size 60 A°) using ethyl acetate-hexane solvent (9:1), was found to be the most effective growth inhibitor (JDHex) against the Leishmania promastigotes and amastigotes. JDHex significantly altered the biochemical parameters (protein, lipid and carbohydrates) in promastigotes followed by the morphological changes, DNA condensation and subsequent apoptosis in L. donovani. In consequent steps, it has been also proved that JDHex reduced the replication of intracellular amastigotes with concomitant release of nitric oxide and pro-inflammatory cytokines, IL-12 and TNF-α in vitro. Significantly, the 50% inhibitory concentration of JDHex was estimated much lower against the intracellular amastigotes (2.5 µg/mL) in comparison to promastigotes (10 µg/mL). JDHex was also found efficient in reducing parasite burden in spleen and liver when treated in vivo and increased the intracellular IFN-γ and decreased the IL-10 in CD4+ T cells in splenocytes of orally treated animals. The results of this study support the importance in exploration of novel anti-leishmanial leads from C. caudatus Geisel. var. tomentosus Hook. against the L. donovani (MHOM/IN/83/AG83) infection. Partial chemical characterization of JDHex revealed the presence of terpenoids. However, the further chemical

  7. Study of antioxidant activity of sheep visceral protein hydrolysate: Optimization using response surface methodology

    Meshginfar, Nasim; Sadeghi-Mahoonak, Alireza; Ziaiifar, Aman Mohammad; Ghorbani, Mohammad; Kashaninejad, Mahdi

    2014-01-01

    BACKGROUND The main objective of this experiment was optimal use of none edible protein source to increase nutritional value of production with high biological function, including antioxidant activity. METHODS Sheep visceral (stomach and intestine) was used as substrate. Response surface methodology (RSM) was used to optimize hydrolysis conditions for preparing protein hydrolysate from the sheep visceral, using alcalase 2.4 l enzyme. The investigated factors were temperature (43-52 °C), time ...

  8. Subcutaneous and visceral fat distribution and daily physical activity: comparison between young and middle aged women.

    Abe, T.; Sakurai, T; Kurata, J; Kawakami, Y; Fukunaga, T.

    1996-01-01

    OBJECTIVE: To examine the effects of aging and physical activity on distribution patterns in subcutaneous and visceral fat. METHODS: Distributions of subcutaneous rat mass at six segments (face and neck, forearm, upper arm, trunk, thigh, and lower leg) were determined by adipose tissue thickness measurements by B mode ultrasonogram and body surface areas. Visceral fat mass was calculated by subtracting subcutaneous fat mass from the total fat mass determined hydrodensitometrically. Measuremen...

  9. Teste de ELISA indireto para diagnóstico sorológico de leishmaniose visceral em canídeos silvestres Indirect ELISA for the serological diagnosis of visceral leishmaniasis in wild canids

    Paulo R.B. Ferreira

    2013-04-01

    assay (ELISA for the serodiagnosis of visceral leishmaniasis (VL in Brazilian species of wild canids is described. Serum and plasma samples from 12 captive wild canids were studied: seven from maned wolves (Chrysocyon brachyurus, three from hoary foxes (Lycalopex vetulus, and two from crab-eating foxes (Cerdocyon thous. Samples from C. brachyurus and L. vetulus, both captive in an endemic area for VL, presenting clinical disease and positivity in Indirect Immunofluorescence Reaction and Polymerase Chain Reaction tests were used as positive controls. The antibody anti-dog IgG and Protein A, both conjugated with horseradish peroxidase, were compared in indirect ELISA tests which detected four (04/12 and three (03/12 seropositive C. brachyurus for anti-Leishmania antibodies, respectively. The ELISA tests were able to clearly distinguish negative from positive samples, as the mean optical density (OD of the negative samples was 4.8 and 15.5 times lower than those of the positive ones either using anti-dog IgG and Protein A, respectively. Samples from three ELISA - positive C. brachyurus were analyzed by Western blotting and identified immunodominant bands of 19, 22, 24, 45 and 66 kDa, among 22 protein bands detected. The ELISAs with protein A and anti-dog IgG showed respectively excellent (Kappa = 1.0; p<0.001 and moderate (Kappa = 0.8; p<0.0015 agreement with the Western blotting assay. The ELISA tests showed to be adequate for screening studies to identify antibody responses, thus indicating contact with Leishmania infection by wild canids.

  10. Evaluation of parasitological examination, kDNA polymerase chain reaction and rK39-based immunochromatography for the diagnosis of visceral leishmaniasis in seropositive dogs from the screening-culling program in Brazil

    Shara Regina-Silva

    2014-08-01

    Full Text Available Introduction Dogs play a primary role in the zoonotic cycle of visceral leishmaniasis (VL. Therefore, the accurate diagnosis of infected dogs, primarily asymptomatic dogs, is crucial to the efficiency of VL control programs. Methods We investigated the agreement of four diagnostic tests for canine visceral leishmaniasis (CVL: parasite detection, either after myeloculture or by direct microscopic examination of tissue imprints; kinetoplast-deoxyribonucleic acid-polymerase chain reaction (kDNA-PCR; and an immunochromatographic test (ICT. An enzyme-linked immunosorbent assay (ELISA and an indirect immunofluorescence test (IFAT, both of which were adopted as part of the screening-culling program in Brazil, were used as reference tests. Our sample set consisted of 44 seropositive dogs, 25 of which were clinically asymptomatic and 19 were symptomatic for CVL according to ELISA-IFAT. Results The highest and lowest test co-positivities were observed for ICT (77.3% and myeloculture (58.1%, respectively. When analyzed together, the overall percentage of co-positive tests was significantly higher for the symptomatic group compared to the asymptomatic group. However, only ICT was significantly different based on the results of a separate analysis per test for each group of dogs. The majority (93.8% of animals exhibited at least one positive test result, with an average of 2.66 positive tests per dog. Half of the symptomatic dogs tested positive for all four tests administered. Conclusions The variability between test results reinforces the need for more efficient and reliable methods to accurately diagnose canine VL, particularly in asymptomatic animals.

  11. Prevalência e epidemiologia da leishmaniose visceral em cães e humanos, na cidade de Cuiabá, Mato Grosso, Brasil Prevalence and epidemiology of visceral Leishmaniasis in dogs and humans in the city Cuiaba, Mato Grosso, Brazil

    Arleana do Bom Parto Ferreira de Almeida

    2010-07-01

    Full Text Available A leishmaniose visceral é uma doença infecciosa endêmica em diversas regiões do Brasil, incluindo o Estado de Mato Grosso. Em Cuiabá, no período de janeiro de 2006 a dezembro de 2008, foi realizada investigação dos casos caninos de infecção por Leishmania sp. por meio de sorologia e citologia, enfocando a sua distribuição geográfica e correlacionando a ocorrência de casos de leishmaniose visceral humana. De 150 cães com suspeita da infecção, 57 (38% foram sorológicos ou parasitologicamente positivos. Observou-se soroprevalência significativa (P≤0,05 nos bairros com renda per capita baixa, além de maior número de casos caninos na regional leste; no entanto, observou-se uma distribuição difusa da doença canina na cidade de Cuiabá, enquanto os casos humanos originaram principalmente na regional norte do município. Esse fato sugere que há risco em todo o município, devendo ser realizados novos estudos soroepidemiológicos, assim como a distribuição vetorial, que promovam maior conhecimento da infecção canina por Leishmania sp, de forma a se gerar medidas adequadas para o controle da doença.Visceral Leishmaniasis is an infectious disease endemic in several regions of Brazil, including the state of Mato Grosso. In Cuiabá, from January 2006 to December 2008, a research was performed in canine cases of infection with Leishmania sp. by serology and cytology, focusing on its geographical distribution, correlating to the occurrence of human visceral Leishmaniasis cases. From 150 dogs with suspected infection, 57 (38% were serological or parasitologically positive. Seroprevalence was observed (P≤0.05 in districts with low per capita income, besides a larger number of canine cases in the East regional, but there was a diffuse distribution of the canine disease in the city of Cuiabá, in contrast to cases focused mainly on human in the northern municipality. This suggests risk throughout the municipality and further

  12. Uveitis secondary to leishmaniasis immune reconstitution syndrome in a HIV-positive patient.

    Davies, Olubanke; Allen, Felicity; Gruener, Anna M; Simons, Rebecca; Graham, Elizabeth M; Larbalestier, Nick

    2016-06-01

    We describe the case of a HIV-positive patient treated for visceral leishmaniasis who developed uveitis as part of a leishmaniasis immune reconstitution syndrome. Visceral leishmaniasis is increasingly found in HIV-positive adults. Its ophthalmic manifestations can range from relatively minor to complicated anterior uveitis, leading to secondary glaucoma and loss of vision. Clinicians caring for people living with HIV should be alert to the complications of leishmaniasis that can occur before and during treatment. PMID:26002317

  13. Autochthonous canine leishmaniasis in Romania: neglected or (re)emerging?

    Mircean, Viorica; Dumitrache, Mirabela Oana; MIRCEAN, MIRCEA; Bolfa, Pompei; Györke, Adriana; Mihalca, Andrei Daniel

    2014-01-01

    Canine leishmaniasis is a vector-borne zoonotic disease caused by the protozoan parasite Leishmania infantum. In Romania between 1955 and 2013, no cases of human autochthonous visceral leishmaniasis were reported. Data regarding canine leishmaniasis is similarly scarce. Since the first report of clinical autochthonous canine leishmaniasis in 1935, there were only three sporadic reports of positive dogs all without any clinical signs. Our study reports the first clinical case of autochthonous ...

  14. Evaluation of kDNA PCR hybridization and ITS1 nPCR methods in different clinical samples for visceral leishmaniasis diagnosis in dogs with and without clinical signs

    Visceral leishmaniasis (VL) in Brazil is caused by Leishmania infantum and dogs are considered the main domestic reservoirs of this parasite. The VL control program in Brazil emphasizes the use of serological surveys, followed by elimination of seropositive dogs. However, serologic tests have limitations in terms of sensitivity and specificity. Molecular methods such as PCR (Polymerase Chain Reaction) associated with hybridization using 32P radiolabeled DNA probes (kDNA PCR hybridization) are useful tools in this scenario, since they are more specific and sensitive than conventional methods. A variety of samples can be employed with PCR; however non-invasive procedures are the most adequate. One of main obstacles for implementation of PCR in the canine visceral leishmaniasis (CVL) diagnosis is the lack of standardization. Few studies up to the moment compared the effectiveness of the different PCR methods and clinical samples available. The objective of this study was to compare the kDNA PCR hybridization and the Internal Transcribed Spacer 1 nested PCR (ITS1 nPCR) methods and four types of clinical samples for the diagnosis of CVL in dogs with and without clinical signs of the disease. The methods were compared using samples of conjunctival swab (SC), bone marrow (BM), skin (S) and peripheral blood (PB). A group of 60 mongrel dogs, all positive in serological and parasitological tests, were equally divided in two groups: S (with clinical signs) and A (without clinical signs). The frequencies of positive results for the kDNA PCR hybridization in the S group were: CS 97% (29/30), BM 83 % (25/30), S 63% (19/30) and PB 4 7% (14/30). By the same method the following results were obtained in the A group: CS 70% (21/30), BM 63% (19/30), S 57% (17/30) and PB 17% (5/30). The ITS1 nPCR allowed the following positivities for the S group: CS 83% (25/30), BM 97% (29/30), S 83% (25/30) and PB 70% (21/30). For the A group the following results were obtained: CS and BM 83% (25

  15. Evaluation of kDNA PCR hybridization and ITS1 nPCR methods in different clinical samples for visceral leishmaniasis diagnosis in dogs with and without clinical signs

    Ferreira, Aline Leandra C.; Carregal, Virginia M.; Leite, Rodrigo S.; Ferreira, Sidney A.; Andrade, Antero Silva R., E-mail: alineleandra@hotmail.com, E-mail: streptos@hotmail.com, E-mail: rleite2005@gmail.com, E-mail: vidasnino@yahoo.com.br, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Lab. de Radiobiologia; Melo, Maria N., E-mail: melo@icb.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Parasitologia

    2013-07-01

    Visceral leishmaniasis (VL) in Brazil is caused by Leishmania infantum and dogs are considered the main domestic reservoirs of this parasite. The VL control program in Brazil emphasizes the use of serological surveys, followed by elimination of seropositive dogs. However, serologic tests have limitations in terms of sensitivity and specificity. Molecular methods such as PCR (Polymerase Chain Reaction) associated with hybridization using {sup 32}P radiolabeled DNA probes (kDNA PCR hybridization) are useful tools in this scenario, since they are more specific and sensitive than conventional methods. A variety of samples can be employed with PCR; however non-invasive procedures are the most adequate. One of main obstacles for implementation of PCR in the canine visceral leishmaniasis (CVL) diagnosis is the lack of standardization. Few studies up to the moment compared the effectiveness of the different PCR methods and clinical samples available. The objective of this study was to compare the kDNA PCR hybridization and the Internal Transcribed Spacer 1 nested PCR (ITS1 nPCR) methods and four types of clinical samples for the diagnosis of CVL in dogs with and without clinical signs of the disease. The methods were compared using samples of conjunctival swab (SC), bone marrow (BM), skin (S) and peripheral blood (PB). A group of 60 mongrel dogs, all positive in serological and parasitological tests, were equally divided in two groups: S (with clinical signs) and A (without clinical signs). The frequencies of positive results for the kDNA PCR hybridization in the S group were: CS 97% (29/30), BM 83 % (25/30), S 63% (19/30) and PB 4 7% (14/30). By the same method the following results were obtained in the A group: CS 70% (21/30), BM 63% (19/30), S 57% (17/30) and PB 17% (5/30). The ITS1 nPCR allowed the following positivities for the S group: CS 83% (25/30), BM 97% (29/30), S 83% (25/30) and PB 70% (21/30). For the A group the following results were obtained: CS and BM 83

  16. Childhood physical abuse predicts stressor-evoked activity within central visceral control regions.

    Banihashemi, Layla; Sheu, Lei K; Midei, Aimee J; Gianaros, Peter J

    2015-04-01

    Early life experience differentially shapes later stress reactivity, as evidenced by both animal and human studies. However, early experience-related changes in the function of central visceral neural circuits that control stress responses have not been well characterized, particularly in humans. The paraventricular nucleus of the hypothalamus (PVN), bed nucleus of the stria terminalis (BNST), amygdala (Amyg) and subgenual anterior cingulate cortex (sgACC) form a core visceral stress-responsive circuit. The goal of this study is to examine how childhood emotional and physical abuse relates to adulthood stressor-evoked activity within these visceral brain regions. To evoke acute states of mental stress, participants (n = 155) performed functional magnetic resonance imaging (fMRI)-adapted versions of the multi-source interference task (MSIT) and the Stroop task with simultaneous monitoring of mean arterial pressure (MAP) and heart rate. Regression analyses revealed that childhood physical abuse correlated positively with stressor-evoked changes in MAP, and negatively with unbiased, a priori extractions of fMRI blood-oxygen level-dependent signal change values within the sgACC, BNST, PVN and Amyg (n = 138). Abuse-related changes in the function of visceral neural circuits may reflect neurobiological vulnerability to adverse health outcomes conferred by early adversity. PMID:24847113

  17. Spatial and seasonal distribution of Lutzomyia longipalpis in Dracena, a city in the western region of the State of São Paulo, Brazil, that is endemic with visceral leishmaniasis

    Marcia Moreira Holcman

    2013-12-01

    Full Text Available Introduction Vector seasonality knowledge is important for monitoring and controlling of vector-borne diseases. Lutzomyia longipalpis (Lu. longipalpis is the main vector of Leishmania (Leishmania infantum Nicolle, 1908, which is the causative agent of visceral leishmaniasis in the Americas. Methods Lu. longipalpis was monitored for 3 consecutive nights each month using light traps from the Centers for Disease Control in the peridomiciles and intradomiciles of 18 residences from January 2005 to December 2012 in the urban area of Dracena, a medium-sized city located in the western region of São Paulo, Brazil. Results A total of 54,820 Lu. longipalpis specimens were collected, and the proportion of positive samples was significantly higher in the peridomiciles than in the intradomiciles (p<0.05 in all 8 years of the study, except for 2005. The vector was present in all study years in the 9 sub-regions of the city, and the male/female ratio ranged from 3.19 to 4.26. The greatest vector abundance occurred in the first semester and peaked in March, confirming its seasonality. Conclusions The maintenance of this high abundance over an 8-year surveillance period demonstrates the vector adaptation to the urban conditions of the city. These characteristics present a major challenge for preventing human and canine contact with the vector and, consequently, controlling the spread of disease.

  18. Correlations between social-emotional feelings and anterior insula activity are independent from visceral states but influenced by culture

    Mary Helen eImmordino-Yang; Xiao-Fei eYang; Hanna eDamasio

    2014-01-01

    The anterior insula (AI) maps visceral states and is active during emotional experiences, a functional confluence that is central to neurobiological accounts of feelings. Yet, it is unclear how AI activity correlates with feelings during social emotions, and whether this correlation may be influenced by culture, as studies correlating real-time AI activity with visceral states and feelings have focused on Western subjects feeling physical pain or basic disgust. Given psychological evidence th...

  19. Drug resistance in leishmaniasis.

    Croft, Simon L; Sundar, Shyam; Fairlamb, Alan H

    2006-01-01

    Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients with visceral leishmaniasis in Bihar State, India, do not respond to treatment with pentavalent antimonials. This is now considered to be due to acquired resistance. Although this class of drugs has been used for over 60 years for leishmaniasis treatment, it is only in the past 2 years that the mechanisms of action and resistance have been identified, related to drug metabolism, thiol metabolism, and drug efflux. With the introduction of new therapies, including miltefosine in 2002 and paromomycin in 2005-2006, it is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy. PMID:16418526

  20. Leishmaniasis Disease

    ... please visit this page: About CDC.gov . Parasites - Leishmaniasis Parasites Home Share Compartir Disease Ulcerative skin lesion, ... border, on a Guatemalan patient who has cutaneous leishmaniasis. (Credit: B. Arana, MERTU, Guatemala) Marked splenomegaly (enlargement/ ...

  1. Localised Leishmaniasis of Oral Mucosa: Report of an Unusual Clinicopathological Entity

    Deepak Passi

    2014-01-01

    Full Text Available The term leishmaniasis comprises of a group of diseases caused by different species of a protozoan called Leishmania. There are three main clinical forms of leishmaniasis: visceral leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis. Exclusive involvement of the mucosa is very rare. We present a case of mucosal leishmaniasis located in the oral cavity. The only manifestation of leishmaniasis disease in the described case was the appearance of an oral lesion. Treatment was provided in the form of antimoniates (oral miltefosine and systemic sodium stibogluconate. A review of literature is made on the subject.

  2. Altered Insula Activity during Visceral Interoception in Weight-Restored Patients with Anorexia Nervosa.

    Kerr, Kara L; Moseman, Scott E; Avery, Jason A; Bodurka, Jerzy; Zucker, Nancy L; Simmons, W Kyle

    2016-01-01

    Anorexia nervosa (AN) is a devastating psychiatric illness that is associated with significant morbidity and mortality. Aberrant visceral interoceptive processing within the insula has been hypothesized to be an important mechanism in AN's pathophysiology due to the theoretical link between interoception and emotional experience. We therefore utilized functional magnetic resonance imaging (fMRI) to examine whether altered insula functioning underlies visceral interoception in AN. Fifteen females with restricting-type AN and 15 healthy control females underwent fMRI while performing an interoceptive attention task during which they focused on sensations in their heart, stomach, and bladder. Participants also performed an anxious rumination task while in the scanner. AN participants were weight-restored and free of psychotropic medications. Two distinct regions of the insula-anterior insula and dorsal mid-insula-exhibited a significant (p<0.05) interaction between group and interoceptive modality. The post hoc analyses revealed that in the dorsal mid-insula the interaction was driven by group differences during stomach interoception (p=0.002, Bonferroni corrected), whereas in the anterior insula the interaction was driven by group differences during heart interoception (p=0.03, Bonferroni corrected). In addition, individuals with AN displayed increased activation during anxious rumination in the dorsal mid-insula, and activation in this region during stomach interoception was correlated with measures of anxiety and psychopathology. This relationship between altered visceral interoception and clinical symptoms in AN suggests an important mechanism for the disorder. Additional research is needed to examine whether interventions targeting visceral interoception may increase the efficacy of treatments for AN. PMID:26084229

  3. Post-kala-azar dermal leishmaniasis associated with AIDS

    Bittencourt Achiléa; Silva Nancy; Straatmann Andréa; Nunes Victor Luiz Correia; Follador Ivonise; Badaró Roberto

    2003-01-01

    Post-kala-azar dermal leishmaniasis (PKDL) is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area) presented with clinical manifestations of visceral leishm...

  4. Espécies de flebotomíneos (Diptera, Psychodidae coletadas em ambiente urbano em municípios com transmissão de Leishmaniose Visceral do Estado de Mato Grosso do Sul, Brasil Species of phlebotomines (Diptera, Psychodidae collected in urban municipalities with transmission of visceral leishmaniasis in Mato Grosso do Sul State, Brazil

    Paulo Silva de Almeida

    2010-06-01

    Full Text Available Os flebotomíneos são os vetores naturais de alguns agentes etiológicos de doenças humanas e de animais, tais como protozoários do gênero Leishmania Ross, 1903. A fauna flebotomínica no Mato Grosso do Sul é relativamente bem conhecida e até o momento compõe-se de 54 espécies. O presente estudo baseia-se no levantamento de flebotomíneos em área urbana de 18 municípios com transmissão de leishmaniose visceral no Estado do Mato Grosso do Sul, com objetivo de verificar as principais espécies e fornecer subsídios para o programa de controle das leishmanioses. As coletas foram realizadas com armadilhas automáticas luminosas, instaladas mensalmente durante três noites consecutivas, das 18:00 horas às 6:00, no período de dois anos. Foram coletadas 36 espécies dentre os 34.799 exemplares identificados. Lutzomyia longipalpis (Lutz & Neiva, 1912 e Nyssomyia whitmani (Antunes, 1939 foram as espécies mais dispersas, a primeira foi encontrada em 16 e a segunda em 15 dos 18 municípios investigados, contudo, Lu. longipalpis foi predominante em todos esses municípios Ny. whitmani não predominou em nenhum deles. Corumbá contribuiu com 40.92% de todos flebotomíneos capturados e nesse município Lutzomyia cruzi (Mangabeira, 1938 respondeu por 92.50% dos exemplares coletados. Ressalta-se que as espécies do gênero Lutzomyia e Nyssomyia whitmani podem estar envolvidas com a transmissão de leishmanioses no Mato Grosso do Sul.The phlebotomine sand flies are the natural vectors of some etiological agents of human and animal diseases, such as the protozoa of the genus Leishmania Ross, 1903. The phlebotomine fauna in Mato Grosso do Sul is relatively well known and so far consists of 54 species. The present study is based on the survey of the phlebotomine fauna of the urban area of the 18 municipal districts with transmission of visceral leishmaniasis, in the state of Mato Grosso do Sul, for the purpose of verifying the main species and

  5. Spatial analysis of visceral leishmaniasis in the municipality of Rondonópolis, in the Brazilian State of Mato Grosso, from 2003 to 2012: human, canine and vector distribution in areas of disease transmission

    Alexander Gonçalves Ferreira Guimarães

    2015-06-01

    Full Text Available INTRODUCTION: Visceral leishmaniasis (VL is a zoonosis of great importance to public health and is considered a neglected disease by the World Health Organization. The disease has expanded and become more prevalent in urban areas in Brazil. METHODS: Geospatial analyses were performed and thematic maps of the triad of the disease were produced for the study period (2003-2012 in the urban area of the municipality of Rondonópolis in the midwestern State of Mato Grosso (MT, Brazil, TerraView 4.2.2 software was used for the analyses. RESULTS: A total of 87.9% of the 186 confirmed human cases of VL were cured. Children between the ages of 1 and 4 were the most affected. Registered deaths were predominant among adults aged 60 years or older. The urban area of the municipality consists of eight strata and 12 census districts include 237 neighborhoods. All sectors had confirmed cases of VL. During the study period, human cases of the disease were recorded in 90 neighborhoods. The 23 deaths from the disease were distributed in 21 neighborhoods. Sandflies carrying the parasite were captured in 192 out of 200 neighborhoods evaluated for the presence of the VL vector. The presence of dogs carrying the parasite was confirmed in, 140 out of 154 surveyed neighborhoods. CONCLUSIONS: The data demonstrated the endemic nature of VL, with a high percentage of infected children, a high distribution of canine infection, and a wide adaptation and dispersal of the vectors in the urban environment. These results, illustrate the process of urbanization of VL in the municipality of Rondonópolis, MT, Brazil.

  6. The Rapid Test Based on Leishmania infantum Chimeric rK28 Protein Improves the Diagnosis of Canine Visceral Leishmaniasis by Reducing the Detection of False-Positive Dogs

    Borja, Lairton Souza; Tuy, Pétala Gardênia da Silva Estrela; Bastos, Leila Andrade; Solcà, Manuela da Silva; Amorim, Leila Denise Alves Ferreira; Veras, Patrícia Sampaio Tavares

    2016-01-01

    Visceral Leishmaniasis (VL) has spread to many urban centers worldwide. Dogs are considered the main reservoir of VL, because canine cases often precede the occurrence of human cases. Detection and euthanasia of serologically positive dogs is one of the primary VL control measures utilized in some countries, including Brazil. Using accurate diagnostic tests can minimize one undesirable consequence of this measure, culling false-positive dogs, and reduce the maintenance of false-negative dogs in endemic areas. In December 2011, the Brazilian Ministry of Health replaced the ELISA (EIE CVL) screening method and Indirect Immunofluorescence Test (IFI CVL) confirmatory method with a new protocol using the rapid DPP CVL screening test and EIE CVL confirmatory test. A study of diagnostic accuracy of these two protocols was done by comparing their performance using serum samples collected from a random sample of 780 dogs in an endemic area of VL. All samples were evaluated by culture and real time PCR; 766 out of the 780 dogs were tested using the previous protocol (IFI CVL + EIE CVL) and all 780 were tested using the current protocol (DPP CVL + EIE CVL). Performances of both diagnostic protocols were evaluated using a latent class variable as the gold standard. The current protocol had a higher specificity (0.98 vs. 0.95) and PPV (0.83 vs. 0.70) than the previous protocol, although sensitivity of these two protocols was similar (0.73). When tested using sera from asymptomatic animals, the current protocol had a much higher PPV (0.63 vs. 0.40) than the previous protocol (although the sensitivity of either protocol was the same, 0.71). Considering a range of theoretical CVL prevalences, the projected PPVs were higher for the current protocol than for the previous protocol for each theoretical prevalence value. The findings presented herein show that the current protocol performed better than previous protocol primarily by reducing false-positive results. PMID:26731098

  7. Factors of poor prognosis of visceral leishmaniasis among children under 12 years of age. A retrospective monocentric study in Belo Horizonte, State of Minas Gerais, Brazil, 2001-2005

    Alexandre Sérgio da Costa Braga

    2013-01-01

    Full Text Available INTRODUTION: A major concern with the visceral leishmaniasis (VL is its high lethality rate, even with proper treatment. Low age, prior malnutrition, disease duration prior to diagnosis, severe anemia, fever for more than 60 days, diarrhea and jaundice are known poor prognostic factors. The goals of this study are to describe the clinical and laboratory characteristics of VL among children under 12 years of age and to identify the factors associated with VL poor outcome. METHODS: Two hundred and fifty children under 12 years of age with confirmed VL admitted to Hospital João Paulo II (FHEMIG, Belo Horizonte, Brazil, between January 2001 and December 2005 were evaluated retrospectively. The primary outcome was the poor clinical evolution: sepsis, and/or pneumonia, and/or urinary tract infection, and/or of bleeding (expect epistaxis, and/or severe neutropenia (neutrophil < 500 cells/mm3. Odds ratio (crude and adjusted and its 95% confidence interval for each variable were calculated. Values less than 0.05 were considered significant. RESULTS: Average age was 3.3 years (3.6 months-11.6 years, 71.2% were younger than 5 years and 47.2% lived in Metropolitan Area of Belo Horizonte. The mean fatality rate was 3.6%. Sixty-six (26.4% patients presented poor evolution. After a multivariate analysis, age <18 months, abnormal respiratory physical examination on hospital admission, and platelets <85,000/mm3 remained associated with increased chance of poor evolution. CONCLUSIONS: The results suggest that patients aged between 12 and 18 months, with platelet counts bellow 85,000/mm3, and respiratory abnormalities at admission should be considered potentially severe.

  8. Distribuição temporal e espacial da leishmaniose visceral em humanos e cães em Belo Horizonte-MG, 1993 a 2007 Temporal and spatial distribution of leishmaniasis in humans and dogs from Belo Horizonte-MG, 1993-2007

    E.G.P. Lopes

    2010-10-01

    Full Text Available O objetivo desta pesquisa foi descrever as análises da série cronológica e determinar a tendência da leishmaniose visceral em humanos e cães para o município de Belo Horizonte, de 1993 a 2007. De 1994, quando surgiram os primeiros casos da doença, até 2007, foram registrados 994 casos humanos autóctones com 116 óbitos. De 1993 a 2007, foram analisadas 1.492.401 amostras de sangue canino com percentual de positividade de 5,9%, utilizando-se os testes de enzyme-linked immunosorbent assay (ELISA como triagem e de imunofluorescência indireta (IFI como confirmatório. As análises indicaram que a leishmaniose visceral apresentou tendência crescente dos coeficientes de incidência em humanos e de prevalência em cães, e observaram-se arquétipos distintos dessa tendência, retratando o momento histórico de transição endêmica. A leishmaniose visceral em cães não apresentou características de distribuição sazonal, e não foi possível concluir a existência ou não de ciclicidade do fenômeno. A leishmaniose visceral em humanos e cães tem ampla distribuição espacial nas nove regionais administrativas com risco diferenciado de acometimento da doença, apesar da presença das fontes de infecção e dos susceptíveis em todo o município.The chronological series analysis and the tendencies of both human and canine visceral leishmaniasis were determined in Belo Horizonte city, from 1993 to 2007. From 1994, when the first cases of the disease were reported, until 2007, 994 human cases were recorded, which led to 116 deaths. From 1993 to 2007, 1,492,401 samples of canine blood were analyzed by the enzyme-linked immunosorbent assay (ELISA as screening test and by the Indirect Immunofluorescence (IFI as confirmatory test. The rate of positive results was 5.9%. The analyses indicated that the visceral leishmaniasis presents a tendency of increasing the coefficient of incidence in humans and prevalence in dogs and different archetypes of

  9. Leishmaniasis as a Manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV-Infected Patients: A Literature Review

    Badaró, Roberto; Gonçalves, Larissa O.; Gois, Luana L.; Maia, Zuinara Pereira Gusmão; Benson, Constance; Grassi, Maria Fernanda Rios

    2016-01-01

    Introduction After the onset of highly active antiretroviral therapy (HAART), some HIV-infected patients present a severe inflammation in response to a latent or a previously treated opportunistic pathogen termed immune reconstitution inflammatory syndrome (IRIS). Few reports of tegumentary and visceral leishmaniasis have been described in association with IRIS. Methods A systematic literature review of IRIS in association with leishmaniasis identified 34 reported cases. Results and Discussion The majority of these occurred in males 4 months following the onset of HAART. The mean CD4 count before HAART was 94 ± 77 cells/mm3, increasing to 5 times the initial value between the onset of HAART and IRIS presentation. Visceral leishmaniasis and post–kala-azar dermal leishmaniasis were the most commonly reported clinical manifestations, followed by tegumentary leishmaniasis and uveitis. Conclusions Commonly found characteristics included cutaneous involvement, regardless of Leishmania species; appearance of lesions unrelated to time of probable Leishmania infection; rapid recovery of CD4 count following HAART; and rapid progression. PMID:25331225

  10. Identification of the visceral pain pathway activated by noxious colorectal distension in mice

    Melinda Kyloh

    2011-02-01

    Full Text Available In patients with irritable bowel syndrome (IBS, visceral pain is evoked more readily following distension of the colorectum. However, the identity of extrinsic afferent nerve pathway that detects and transmits visceral pain from the colorectum to the spinal cord is unclear. In this study, we identified which extrinsic nerve pathway(s underlies nociception from the colorectum to the spinal cord of rodents. Electromyogram (EMG recordings were made from the transverse oblique abdominal muscles in anesthetized wild type (C57BL/6 mice and acute noxious intraluminal distension (100-120 mmHg applied to the terminal 15mm of rectum to activate visceromotor responses (VMRs. Cutting the lumbar colonic nerves in vivo had no detectable effect on the VMRs evoked by colorectal distension. Lesioning right or left hypogastric nerves also failed to reduce VMRs. However, lesioning left and right branches of the rectal nerves completely abolished the VMRs, regardless of whether the lumbar colonic or hypogastric nerves were severed. Electrical stimulation applied to either the lumbar colonic or hypogastric nerves in vivo, failed to elicit a VMR. In contrast, electrical stimulation (2-5Hz, 0.4ms, 60V applied to the rectum reliably elicited VMRs, which were abolished by selective lesioning of the rectal nerves. DiI retrograde labelling from the colorectum labelled sensory neurons only in dorsal root ganglia (DRG of the lumbosacral region of the spinal cord. In contrast, injection of DiI into the mid to proximal colon labelled sensory neurons in DRG primarily of the lower thoracic level (T8-L4 of the spinal cord. The visceral pain pathway activated by acute noxious distension of the terminal 15 mm of mouse rectum is transmitted predominantly, if not solely, through rectal/pelvic afferent nerve fibres to the spinal cord. The sensory neurons of this spinal afferent pathway lie in the lumbosacral region of the spinal cord, primarily at the level of S2 and S3.

  11. Monitoring of Lutzomyia longipalpis Lutz & Neiva, 1912 in an area of intense transmission of visceral leishmaniasis in Rio Grande do Norte, Northeast Brazil Monitoramento de Lutzomyia longipalpis Lutz & Neiva, 1912 em área de transmissão intensa de leishmaniose visceral no Rio Grande do Norte, Nordeste do Brasil

    Sthenia Santos Albano Amóra

    2010-03-01

    Full Text Available Urban increase of visceral leishmaniasis (VL in Brazil is associated with the adaptation of its vector, Lutzomyia longipalpis, to environments modified by humans. The present study reports the results of an entomological monitoring of L. longipalpis and the effect of environmental variables on its population density. Sandflies were captured in the municipality of Mossoró, State of Rio Grande do Norte, Northeastern Brazil, from January 2005 to December 2006. Two CDC light traps were placed monthly for four consecutive nights in the peridomicile of selected households. Data analysis was based on the chi-square test and linear regression. A total of 2,087 sandflies were captured, 99.86% of which were L. longipalpis. A higher proportion of females were captured (p No Brasil, o crescimento urbano da leishmaniose visceral (LV está associado com a adaptação do seu vetor, Lutzomyia longipalpis, aos ambientes modificados pelo homem. Este estudo relata a vigilância entomológica de L. longipalpis e os efeitos das variáveis ambientais sobre a sua densidade populacional. Os flebotomíneos foram capturados no município de Mossoró, Rio Grande do Norte, no Nordeste do Brasil, a partir de janeiro de 2005 a dezembro de 2006. Duas armadilhas tipo CDC foram colocadas mensalmente durante quatro noites consecutivas no peridomicílio das casas escolhidas. A análise dos dados foi baseada no teste Qui-quadrado e regressão linear. Um total de 2.087 flebotomíneos foram capturados, dos quais 99,86% foram L. longipalpis. Mais fêmeas do que machos foram capturados (p < 0,05. Na análise mensal das variáveis ambientais a temperatura, umidade relativa e a chuva não tiveram impacto significativo sobre a densidade populacional de L. longipalpis. No entanto, houve diferenças sazonais: aproximadamente 70% dos flebotomíneos foram capturados durante a estação chuvosa (p < 0,05. Assim, L. longipalpis, a espécie predominante, representa um risco à saúde p

  12. Assessment of sand fly (Diptera, Psychodidae control using cypermethrin in an endemic area for visceral leishmaniasis, Montes Claros, Minas Gerais State, Brazil Avaliação do controle de flebotomíneos (Diptera, Psychodidae usando cipermetrina em área endêmica para leishmaniose visceral, Montes Claros, Minas Gerais, Brasil

    Ricardo Andrade Barata

    2011-11-01

    Full Text Available Montes Claros in Minas Gerais State, Brazil, was considered an intense transmission area for visceral leishmaniasis. This study evaluated sand fly fauna after insecticide application. Captures were performed in 10 districts from September 2005 to August 2006 with CDC light traps inside and outside each residence. Cypermethrin was sprayed in two cycles during November/2005 and May/2006. The 636 specimens collected, belonging to 10 species, were predominantly Lutzomyia longipalpis (79%, and most frequently males (70%. The highest percentage of specimens were captured in areas surrounding domiciles (85.8%. The main species were observed to be sensitive to treatment with the insecticide. The results showed a reduction in the number of sand flies collected after use of cypermethrin in homes and annexes, and with residual effect lasting from two to four months.Montes Claros foi considerada área de transmissão intensa para leishmaniose visceral no Estado de Minas Gerais, Brasil. Este trabalho avaliou a fauna de flebotomíneos após a aplicação do inseticida. Entre setembro de 2005 e agosto de 2006, foram realizadas capturas com 20 armadilhas luminosas CDC em 10 bairros do município, no intra e no peridomicílio de cada residência. Dois ciclos de borrifação com cipermetrina foram realizados nos meses de novembro/2005 e maio/2006. Coletou-se 636 exemplares pertencentes a 10 espécies, com predominância de Lutzomyia longipalpis (79%. Machos foram coletados com maior frequência (70%. O peridomicílio apresentou a maior porcentagem dos espécimens capturados (85,8%. Observou-se que as principais espécies foram sensíveis ao tratamento com o inseticida. Os resultados mostraram uma redução do número de flebotomíneos coletados devido ao uso de cipermetrina nos domicílios e seus anexos, mas com efeito residual atuante entre dois e quatro meses.

  13. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity

    II Kim Jae

    2010-10-01

    Full Text Available Abstract Background Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism. Methods In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB. Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test. Results Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight and histological analysis of the lung metastasis (gross analysis and histological staining. Reduced expression of Cox-2 (mRNA and protein from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity. Conclusions Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells.

  14. Post-kala-azar dermal leishmaniasis associated with AIDS

    Bittencourt Achiléa

    2003-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

  15. Post-kala-azar dermal leishmaniasis associated with AIDS

    Bittencourt Achiléa

    2002-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

  16. Impact of leishmaniasis on public health

    L. B Camargo

    2006-01-01

    Full Text Available Leishmaniasis is a parasitic zoonosis caused by protozoans of the genus Leishmania transmitted by insects known as phlebotomines, which are found in wild or urban environments. It affects domestic and wild animals and transmission to man happens by accident. The disease occurs in tropical and sub-tropical areas, mainly in Asia, Europe, Africa, and the Americas. There are two forms that affect man: American cutaneous leishmaniasis (ACL and American visceral leishmaniasis (AVL. The latter is caused by three species of Leishmania: Leishmania (Leishmania donovani, Leishmania (Leishmania infantum, and Leishmania (Leishmania chagasi, which are grouped in the Leishmania (Leishmania donovani complex. Wild reservoir hosts of L. chagasi known so far are foxes and marsupials. In domestic environment, dogs are the most important reservoir hosts and sources of infection to the vectors Lutzomyia longipalpis. Leishmaniasis is difficult to control, causing epidemic outbreaks, thus being an important public health problem. Due to lesions caused by the mucocutaneous type and the severity of those caused by the visceral type in humans, visceral leishmaniasis is one of the main public health concerns. This paper is part of the monograph presented at the end of the residency program in the field of Zoonosis and Public Health at the School of Veterinary Sciences and Animal Husbandry, São Paulo State University, UNESP, Botucatu, São Paulo State, Brazil, in 2005.

  17. Leishmaniose visceral no Rio de Janeiro: 1 - Flebotomíneos da área de procedência de caso humano autóctone Visceral leishmaniasis in Rio de Janeiro: 1-Phlebotomines from the area of origin of an autochthonous human case

    Miguel Alves de Souza

    1981-06-01

    sp. 2 (0.2%. L. longipalpis were predominant at altitudes much higher than 100 merters either in chicken houses or piggeries. Most of them were collected form 6:00 to 9:00 pm, but occasionally were captured also from 3:00 to 5: pm. L. intermedia were predominant at altitudes much lower than 100 meters. They were captured more frequently in piggeries than in chicken houses, compared to L. longipalpis. The authors stress the necessity to implement control measures since there is a potential risk of visceral leishmaniasis transmission in areas near Rio de Janeiro city.

  18. Altered brain activation to colorectal distention in visceral hypersensitive maternal-separated rats

    Wouters, Mira; van Wanrooy, Sander; Casteels, Cindy; Nemethova, A; de Vries, Annick; Van Oudenhove*, Lukas; van den Wijngaard, R. M.; Van Laere, Koen; Boeckxstaens, Guy

    2012-01-01

    Background  Early life trauma can predispose to increased visceral pain perception. Human neuroimaging studies emphasize that altered brain processing may contribute to increased visceral sensitivity. The aim of our study was to evaluate brain responses to painful visceral stimuli in maternal-separated rats before and after acute stress exposure in vivo. Methods  H(2) (15) O microPET scanning was performed during colorectal distention in maternal-separated rats before and after water avoidanc...

  19. The pathogenesis of post kala-azar dermal leishmaniasis from the field to the molecule: does ultraviolet light (UVB) radiation play a role?

    Ismail, A; Khalil, E A G; Musa, A M;

    2006-01-01

    Post kala-azar dermal leishmaniasis (PKDL) is a dermatosis caused by persistence of Leishmania donovani parasites in the skin following apparently successful treatment of visceral leishmaniasis. The distribution of PKDL lesions in Sudanese patients often mirrors the clothing habits of those...... affected. It is most severe in or confined to the sun-exposed parts of the skin. It is well established that elimination of Leishmania parasites requires activation of parasitised macrophages by a Th1 immune response and that the latter is depressed by ultraviolet light (UVB). In this paper, we...

  20. NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs during inflammation induced visceral hypersensitivity

    Caudle Robert M

    2009-09-01

    Full Text Available Abstract Background Visceral hypersensitivity is a clinical observation made when diagnosing patients with functional bowel disorders. The cause of visceral hypersensitivity is unknown but is thought to be attributed to inflammation. Previously we demonstrated that a unique set of enteric neurons, colospinal afferent neurons (CANs, co-localize with the NR1 and NR2D subunits of the NMDA receptor as well as with the PAR2 receptor. The aim of this study was to determine if NMDA and PAR2 receptors expressed on CANs contribute to visceral hypersensitivity following inflammation. Recently, work has suggested that dorsal root ganglion (DRG neurons expressing the transient receptor potential vanilloid-1 (TRPV1 receptor mediate inflammation induced visceral hypersensitivity. Therefore, in order to study CAN involvement in visceral hypersensitivity, DRG neurons expressing the TRPV1 receptor were lesioned with resiniferatoxin (RTX prior to inflammation and behavioural testing. Results CANs do not express the TRPV1 receptor; therefore, they survive following RTX injection. RTX treatment resulted in a significant decrease in TRPV1 expressing neurons in the colon and immunohistochemical analysis revealed no change in peptide or receptor expression in CANs following RTX lesioning as compared to control data. Behavioral studies determined that both inflamed non-RTX and RTX animals showed a decrease in balloon pressure threshold as compared to controls. Immunohistochemical analysis demonstrated that the NR1 cassettes, N1 and C1, of the NMDA receptor on CANs were up-regulated following inflammation. Furthermore, inflammation resulted in the activation of the PAR2 receptors expressed on CANs. Conclusion Our data show that inflammation causes an up-regulation of the NMDA receptor and the activation of the PAR2 receptor expressed on CANs. These changes are associated with a decrease in balloon pressure in response to colorectal distension in non-RTX and RTX lesioned

  1. Supplementation of host response by targeting nitric oxide to the macrophage cytosol is efficacious in the hamster model of visceral leishmaniasis and adds to efficacy of amphotericin B.

    Pandya, Sanketkumar; Verma, Rahul Kumar; Khare, Prashant; Tiwari, Brajendra; Srinivasarao, Dadi A; Dube, Anuradha; Goyal, Neena; Misra, Amit

    2016-08-01

    We investigated efficacy of nitric oxide (NO) against Leishmania donovani. NO is a mediator of host response to infection, with direct parasiticidal activity in addition to its role in signalling to evoke innate macrophage responses. However, it is short-lived and volatile, and is therefore difficult to introduce into infected cells and maintain inracellular concentrations for meaningful periods of time. We incorporated diethylenetriamine NO adduct (DETA/NO), a prodrug, into poly(lactide-co-glycolide) particles of ∼200 nm, with or without amphotericin B (AMB). These particles sustained NO levels in mouse macrophage culture supernatants, generating an area under curve (AUC0.08-24h) of 591.2 ± 95.1 mM × h. Free DETA/NO resulted in NO peaking at 3 h and declining rapidly to yield an AUC of 462.5 ± 193.4. Particles containing AMB and DETA/NO were able to kill ∼98% of promastigotes and ∼76% of amastigotes in 12 h when tested in vitro. Promastigotes and amastigotes were killed less efficiently by particles containing a single drug- either DETA/NO (∼42%, 35%) or AMB (∼90%, 50%) alone, or by equivalent concentrations of drugs in solution. In a pre-clinical efficacy study of power >0.95 in the hamster model, DETA/NO particles were non-inferior to Fungizone® but not Ambisome®, resulting in significant (∼73%) reduction in spleen parasites in 7 days. Particles containing both DETA/NO and AMB were superior (∼93% reduction) to Ambisome®. We conclude that NO delivered to the cytosol of macrophages infected with Leishmania possesses intrinsic activity and adds significantly to the efficacy of AMB. PMID:27183429

  2. Leishmaniasis FAQs

    ... have become infected in various countries, such as Iraq and Afghanistan Back To Top Is leishmaniasis found ... source: Global Health - Division of Parasitic Diseases and Malaria Notice: Linking to a non-federal site does ...

  3. T-cell response in human leishmaniasis

    Kharazmi, A; Kemp, K; Ismail, A;

    1999-01-01

    In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered...... from cutaneous leishmaniasis (CL) responded by IFN-gamma production following stimulation with Leishmania antigens whereas cells from patients recovered from visceral leishmaniasis (VL) showed a mixed pattern of IFN-gamma and IL-4 responses. The cells producing these cytokines were predominantly CD4......+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans....

  4. Genetically Modified Organisms and Visceral Leishmaniasis

    Chhajer, Rudra; Ali, Nahid

    2014-01-01

    Vaccination is the most effective method of preventing infectious diseases. Since the eradication of small pox in 1976, many other potentially life compromising if not threatening diseases have been dealt with subsequently. This event was a major leap not only in the scientific world already burdened with many diseases but also in the mindset of the common man who became more receptive to novel treatment options. Among the many protozoan diseases, the leishmaniases have emerged as one of the ...

  5. RAPID SCREENING WITH A RECOMBINANT ANTIGEN (rK39) FOR DIAGNOSIS OF VISCERAL LEISHMANIASIS USING DIPSTICK%用重组rK39抗原试纸条快速诊断内脏利什曼病

    瞿靖琦; S.G.Reed; K.-P.Chang; 管立人; 依马木苏里单; 左新平; 柴君杰; 陈生邦; Shinichiro Kawazu; Ken Katakura; Yoshigeru Matsumoto

    2000-01-01

    [Objective] To evaluate the diagnostic value of the recombinant antigen of 39 amino acid repeats encoded by a kinesin-like gene of Leishmania changasi (rK39) in serodiagnosis of visceral leishmaniasis (VL). [Methods] In Kashi, Xinjiang, 13 VL patients with splenomegaly and bone marrow aspirate culture positive were subjected to dipstick assay. A drop of whole blood or serum from patient was placed at the absorbing pad at the bottom of the dipstick.Flooding of the bottom protein with buffer allows serum proteins to migrate upwards, producing the positive band and Western blot analysis of rK39 subsequently performed with the sera collected. [Results] The end-point titers of antirK39 antibodies of these sera were determined by ELISA and found to fall within the range of 10-2 to 10-4, which were consistent with the intensity of their reaction with rK39 in dipstick assay. The positive sera could also recognize the specific rK39 band as analyzed by Western blot analysis. [Conclusion] The rK39 dipstick assay is more rapid, specific, sensitive and less invasive than the conventional methods of diagnosis for VL in the areas of low endemicity.%[目的]评价以恰氏利氏曼原虫类kinesin基因中编码39个氨基酸的基因片段(rK39)为重组抗原,用于血清学诊断内脏利什曼病的价值.[方法]在新疆喀什地区对13例经脾检和骨髓穿刺阳性的内脏利什曼病患者,取一滴病人全血或血清滴在rK39抗原试纸条底部的吸收垫上,血清中蛋白随缓冲液向试纸条上部移动,其中相应特异抗体可与rK39抗原带结合,而产生阳性条带.同时,本文亦用相同阳性血清作了关于rK39抗原的Western印迹分析对照.[结果]ELISA分析显示病人血清抗体滴度在10-2~10-4,与所见到的rK39试纸条上的反应强度符合.Western印迹分析亦显示阳性血清可识别rK39蛋白条带.[结论]与传统诊断内脏利什曼病方法相比较,rK39试纸条更快速,特异,灵敏和低损伤性,可用

  6. An epidemiological survey of visceral leishmaniasis in Gholtoghrakh Township of Payzawat County of Xinjiang Uygur Autonomous Region%新疆维吾尔自治区伽师县卧里托格拉克乡居民内脏利什曼病流行现况调查

    伊斯拉音·乌斯曼; 麦麦提艾力·阿卜力米提; 姚新华; 左新平; 顾灯安; 兰勤娴; 童苏祥; 李雄; 张仪; 茹孜古丽·朱马洪; 麦麦提敏·艾海提

    2010-01-01

    Objective To investigate the epidemiological status of visceral leishmaniasis in Payzawat County of Xinjiang Uygur Autonomous Region. Methods Based on a hint of possible existence of patients, a retrospective survey was carried out house by house to find cases with suspected signs/symptoms of the disease,meanwhile, a survey on current status was conducted, including physical examination (liver and spleen palpation) on those less than 3 years old, leishmanin skin test and rk39 immunochromatographic strip test on part of the residents. Bone marrow smears were examined for the cases with clinical signs/symptoms and positive rk39 strip test. Sandflies were collected using routine methods in and around the area, identified, and dissected to find infection of promastigotes. Results Leishmanin skin test was performed in 149 people with a positive rate of 68.46% (102/149) among them a positive rate of 11.76% (2/17) under 3 years old and a positive rate of 75.76% (100/132) between 4-75 years old. Of the 15 children under 3 years old with a negative skin test,one showed positive for rk39 strip test, and so confirmed as visceral leishmaniasis. There were 52 cases with a history of suspected signs/symptoms including 2 deaths, traced back as visceral leishmaniasis in 2001-2008.Total 374 sandfies were identified as Phlebotomus wui, and natural infection with promastigotes was found in 3 sandfies. Conclusion Visceral leishmaniasis is still prevalence in Payzawat County.%目的 调查新疆维吾尔自治区伽师县内脏利什曼病流行现况.方法 采用回顾性调查和现况调查相结合,对伽师县卧里托格拉克乡20村1组所有居民进行入户调查.调查内容包括既往有无疑似内脏利什曼病病史,部分居民进行利什曼素皮内试验,对3岁以下婴幼儿皮内试验阴性者进行查体(触诊肝、脾)和rk39免疫层析试条检测.在居民住宅内、外捕集白蛉,解剖鉴定并检查前鞭毛体有无自然感染.结果

  7. Leishmaniasis in HIV infection.

    Paredes R

    2003-01-01

    Full Text Available Herein we review the particular aspects of leishmaniasis associated with HIV infection. The data in this review are mainly from papers identified from PubMed searches and from papers in reference lists of reviewed articles and from the authors′ personal archives. Epidemiological data of HIV/Leishmania co-infection is discussed, with special focus on the influence of Highly Active Antiretroviral Therapy (HAART on incidence of leishmaniasis and transmission modalities. Microbiological characteristics, pathogenesis, clinical presentation and specific treatment of the co-infection are also presented.

  8. An overview of paediatric leishmaniasis.

    Kafetzis D

    2003-01-01

    Full Text Available Leishmaniasis, a parasitic disease transmitted by the bite of some species of sandflies affects various age groups depending on the infecting Leishmania species, geographic location, disease reservoir, and host immunocompetence. Visceral leishmaniasis is the most severe form of the disease affecting children. The extent and presentation of the disease depend on several factors, including the humoral and cell-mediated immune response of the host, the virulence of the infecting species, and the parasite burden. Children are at greater risk than adults in endemic areas. Malnutrition contributes to the development of disease, and incomplete therapy of initial disease is a risk factor for recurrence of leishmaniasis. Children usually present with intermittent fever, paleness, refusal to feed or anorexia, weight loss, and abdominal distension. Splenomegaly, hepatomegaly, lymph node enlargement, thrombocytopaenia, anaemia, leukopaenia and hypergammaglobulinemia are the most common findings in Paediatric leishmaniasis. Molecular methods appear to offer the promise of accurate non-invasive tools for the diagnosis of Leishmaniasis. Till these methods are evaluated, definite diagnosis will rely on the demonstration of the infecting parasite in various tissues. World-wide, with the notable exception of India, pentavalent antimonial compounds remain the most effective and the most affordable therapy for this disease. Lipid formulations of amphotericin B were assessed as short duration treatment and were proved to be effective. However, their cost precludes their wide use in developing countries. Miltefosine, a new oral agent, might prove effective, safe, and affordable. Strategies aimed at control of the micro-population of sandflies, eradication of canine leishmaniasis, and offering personal protection against sandfly bites, together with health education programs in developing countries, can help control the disease. Development of an effective vaccine

  9. Correlations between social-emotional feelings and anterior insula activity are independent from visceral states but influenced by culture

    Mary Helen eImmordino-Yang

    2014-09-01

    Full Text Available The anterior insula (AI maps visceral states and is active during emotional experiences, a functional confluence that is central to neurobiological accounts of feelings. Yet, it is unclear how AI activity correlates with feelings during social emotions, and whether this correlation may be influenced by culture, as studies correlating real-time AI activity with visceral states and feelings have focused on Western subjects feeling physical pain or basic disgust. Given psychological evidence that social-emotional feelings are cognitively constructed within cultural frames, we asked Chinese and American participants to report their feeling strength to admiration and compassion-inducing narratives during fMRI with simultaneous electrocardiogram recording. Trial-by-trial, cardiac arousal and feeling strength correlated with ventral and dorsal AI activity bilaterally but predicted different variance, suggesting that interoception and social-emotional feeling construction are concurrent but dissociable AI functions. Further, although the variance that correlated with cardiac arousal did not show cultural effects, the variance that correlated with feelings did. Feeling strength was especially associated with ventral AI activity (the autonomic modulatory sector in the Chinese group but with dorsal AI activity (the visceral-somatosensory/cognitive sector in an American group not of Asian descent. This cultural group difference held after controlling for posterior insula activity and was replicated. A bi-cultural East-Asian American group showed intermediate results. The findings help elucidate how the AI supports feelings and suggest that previous reports that dorsal AI activation reflects feeling strength are culture related. More broadly, the results suggest that the brain’s ability to construct conscious experiences of social emotion is less closely tied to visceral processes than neurobiological models predict and at least partly open to cultural

  10. Correlations between social-emotional feelings and anterior insula activity are independent from visceral states but influenced by culture.

    Immordino-Yang, Mary Helen; Yang, Xiao-Fei; Damasio, Hanna

    2014-01-01

    The anterior insula (AI) maps visceral states and is active during emotional experiences, a functional confluence that is central to neurobiological accounts of feelings. Yet, it is unclear how AI activity correlates with feelings during social emotions, and whether this correlation may be influenced by culture, as studies correlating real-time AI activity with visceral states and feelings have focused on Western subjects feeling physical pain or basic disgust. Given psychological evidence that social-emotional feelings are cognitively constructed within cultural frames, we asked Chinese and American participants to report their feeling strength to admiration and compassion-inducing narratives during fMRI with simultaneous electrocardiogram recording. Trial-by-trial, cardiac arousal and feeling strength correlated with ventral and dorsal AI activity bilaterally but predicted different variance, suggesting that interoception and social-emotional feeling construction are concurrent but dissociable AI functions. Further, although the variance that correlated with cardiac arousal did not show cultural effects, the variance that correlated with feelings did. Feeling strength was especially associated with ventral AI activity (the autonomic modulatory sector) in the Chinese group but with dorsal AI activity (the visceral-somatosensory/cognitive sector) in an American group not of Asian descent. This cultural group difference held after controlling for posterior insula (PI) activity and was replicated. A bi-cultural East-Asian American group showed intermediate results. The findings help elucidate how the AI supports feelings and suggest that previous reports that dorsal AI activation reflects feeling strength are culture related. More broadly, the results suggest that the brain's ability to construct conscious experiences of social emotion is less closely tied to visceral processes than neurobiological models predict and at least partly open to cultural influence and

  11. Identification of the Visceral Pain Pathway Activated by Noxious Colorectal Distension in Mice

    Kyloh, Melinda; Nicholas, Sarah; Zagorodnyuk, Vladimir P.; Brookes, Simon J.; Spencer, Nick J.

    2011-01-01

    In patients with irritable bowel syndrome, visceral pain is evoked more readily following distension of the colorectum. However, the identity of extrinsic afferent nerve pathway that detects and transmits visceral pain from the colorectum to the spinal cord is unclear. In this study, we identified which extrinsic nerve pathway(s) underlies nociception from the colorectum to the spinal cord of rodents. Electromyogram recordings were made from the transverse oblique abdominal muscles in anesthe...

  12. Identification of the visceral pain pathway activated by noxious colorectal distension in mice

    NickJSpencer

    2011-01-01

    In patients with irritable bowel syndrome (IBS), visceral pain is evoked more readily following distension of the colorectum. However, the identity of extrinsic afferent nerve pathway that detects and transmits visceral pain from the colorectum to the spinal cord is unclear. In this study, we identified which extrinsic nerve pathway(s) underlies nociception from the colorectum to the spinal cord of rodents. Electromyogram (EMG) recordings were made from the transverse oblique abdominal muscle...

  13. Childhood physical abuse predicts stressor-evoked activity within central visceral control regions

    Banihashemi, Layla; Sheu, Lei K.; Midei, Aimee J.; Gianaros, Peter J.

    2014-01-01

    Early life experience differentially shapes later stress reactivity, as evidenced by both animal and human studies. However, early experience-related changes in the function of central visceral neural circuits that control stress responses have not been well characterized, particularly in humans. The paraventricular nucleus of the hypothalamus (PVN), bed nucleus of the stria terminalis (BNST), amygdala (Amyg) and subgenual anterior cingulate cortex (sgACC) form a core visceral stress-responsi...

  14. Leishmaniasis in Turkey.

    Ok, U Z; Balcioğlu, I C; Taylan Ozkan, A; Ozensoy, S; Ozbel, Y

    2002-10-01

    Leishmaniases are widespread in most countries in the Mediterranean basin, including Turkey. Two forms are observed in Turkey; Leishmania infantum is responsible from visceral leishmaniasis (VL), and L. tropica causes cutaneous leishmaniasis (CL). Phlebotomus sergenti, P. papatasi, P. major and P. syriacus are considered to be the probable vectors, and dogs are the main reservoir of L. infantum, while P. sergenti is the main suspected vector of L. tropica.VL is sporadically seen mainly in the Aegean, Mediterranean, and Central Anatolia Regions, but CL is endemic, especially in the Southeastern and Mediterranean Regions. Major touristic sites are free of both infections, and no infection is reported in any tourist. Mean number of annual VL and CL cases reported to Ministry of Health are 40 and 1,204, respectively, in the last four years. These data suggest that both VL and CL represent a public health problem in Turkey, but a decline is observed in the number of cases with both infections in recent years. PMID:12387909

  15. Plant-derived compounds in treatment of leishmaniasis

    Oryan, A.

    2015-01-01

    Leishmaniasis is a neglected public health problem caused by the protozoan species belonging to the genus Leishmania affecting mostly the poor populations of developing countries. The causative organism is transmitted by female sandflies. Cutaneous, mucocutaneous, and visceral clinical manifestations are the most frequent forms of leishmaniasis. Chemotherapy still relies on the use of pentavalent antimonials, amphotericin B, paromomycin, miltefosin and liposomal amphotericin B. However, the a...

  16. ω3-PUFAs exert anti-inflammatory activity in visceral adipocytes from colorectal cancer patients.

    Massimo D'Archivio

    Full Text Available OBJECTIVE: The aim of this study was to correlate specific fatty acid profiles of visceral white adipose tissue (WAT with inflammatory signatures potentially associated with colorectal cancer (CRC. METHODS: Human adipocytes were isolated from biopsies of visceral WAT from 24 subjects subdivided in four groups: normal-weight (BMI 22.0-24.9 Kg/m2 and over-weight/obese (BMI 26.0-40.0 Kg/m2, affected or not by CRC. To define whether obesity and/or CRC affect the inflammatory status of WAT, the activation of the pro-inflammatory STAT3 and the anti-inflammatory PPARγ transcription factors as well as the expression of adiponectin were analyzed by immunoblotting in adipocytes isolated from each group of subjects. Furthermore, to evaluate whether differences in inflammatory WAT environment correlate with specific fatty acid profiles, gas-chromatographic analysis was carried out on WAT collected from all subject categories. Finally, the effect of the ω3 docosahexaenoic acid treatment on the balance between pro- and anti-inflammatory factors in adipocytes was also evaluated. RESULTS: We provide the first evidence for the existence of a pro-inflammatory environment in WAT of CRC patients, as assessed by the up-regulation of STAT3, and the concomitant decrease of PPARγ and adiponectin with respect to healthy subjects. WAT inflammatory status was independent of obesity degree but correlated with a decreased ω3-/ω6-polyunsaturated fatty acid ratio. These observations suggested that qualitative changes, other than quantitative ones, in WAT fatty acid may influence tissue dysfunctions potentially linked to inflammatory conditions. This hypothesis was further supported by the finding that adipocyte treatment with docosahexaenoic acid restored the equilibrium between STAT3 and PPARγ. CONCLUSION: Our results suggest that adipocyte dysfunctions occur in CRC patients creating a pro-inflammatory environment that might influence cancer development. Furthermore

  17. Activation of corticotropin-releasing factor neurons and microglia in paraventricular nucleus precipitates visceral hypersensitivity induced by colorectal distension in rats.

    Zhang, Gongliang; Yu, Le; Chen, Zi-Yang; Zhu, Jun-Sheng; Hua, Rong; Qin, Xia; Cao, Jun-Li; Zhang, Yong-Mei

    2016-07-01

    Visceral hypersensitivity is a major contributor to irritable bowel syndrome and other disorders with visceral pain. Substantial evidence has established that glial activation and neuro-glial interaction play a key role in the establishment and maintenance of visceral hypersensitivity. We recently demonstrated that activation of spinal microglial toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling facilitated the development of visceral hypersensitivity in a rat model developed by neonatal and adult colorectal distensions (CRDs). Hypothalamic paraventricular nucleus (PVN) plays a pivotal role in the pathogenesis of chronic pain. In this study, we examined the mechanism by which microglia and neurons in PVN establish and maintain visceral hypersensitivity and the involvement of TLR4 signaling. Visceral hypersensitivity was precipitated by adult colorectal distension (CRD) only in rats that experienced neonatal CRDs. Visceral hypersensitivity was associated with an increase in the expression of c-fos, corticotropin-releasing factor (CRF) protein and mRNA in PVN, which could be prevented by intra-PVN infusion of lidocaine or small interfering RNA targeting the CRF gene. These results suggest PVN CRF neurons modulate visceral hypersensitivity. Adult CRD induced an increase in the expression of Iba-1 (a microglial marker), TLR4 protein, and its downstream effectors MyD88, NF-κB, as well as proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) only in rats that experienced neonatal CRDs. Intra-PVN infusion of minocycline, a nonselective microglial inhibitor, attenuated the hyperactivity of TLR4 signaling cascade, microglial activation, and visceral hypersensitivity. Taken together, these data suggest that neonatal CRDs induce a glial activation in PVN. Adult CRD potentiates the glial and CRF neuronal activity, and precipitates visceral hypersensitivity and pain. TLR4 signaling and

  18. Recent advances in the diagnosis of leishmaniasis.

    Singh S

    2003-01-01

    Full Text Available Leishmaniasis is a parasitic disease caused by a haemoflagellate Leishmania. There are more than 21 species causing human infection. The infection is transmitted to humans through the bites of female sandflies belonging to 30 species. The disease manifests mainly in 3 forms: the visceral, the cutaneous and the mucocutaneous leishmaniasis. The diagnosis of visceral form is conventionally made by the demonstration of amastigotes of the parasite in the aspirated fluid from the bone marrow, the spleen, and rarely from the lymph nodes, or the liver. The parasite demonstration and isolation rates are rather poor from cutaneous and mucocutaneous lesions due to low parasite load and high rate of culture contamination. Recently several recombinant proteins have been developed to accomplish accurate diagnosis. Recombinant kinesin protein of 39 kDa called rK 39 is the most promising of these molecules. The antigen used in various test formats has been proved highly sensitive and specific for visceral leishmaniasis. It is useful in the diagnosis of HIV-Leishmania co-infection and as a prognostic marker. Molecular techniques targeting various genes of the parasite have also been reported, the PCR being the most common molecular technique successfully used for diagnosis and for differentiation of species.

  19. 2014年新疆伽师县内脏利什曼病暴发的调查分析%Investigation on the Outbreak of Visceral Leishmaniasis in 2014 in Jiashi County of Xinjiang

    伊斯拉音·乌斯曼; 阿迪力·司马义; 凯赛尔·克尤木; 麦麦提艾力·阿卜力米提; 季芳; 侯岩岩; 张松; 亚力坤·买买提依明; 茹孜古丽·朱马洪

    2015-01-01

    visceral leishmaniasis ( VL ) outbreak in Jiashi County of Xinjiang Uygur Autonomous Region in 2014, and provide basis for VL prevention and control strategies. Methods Data on VL epidemic situation in Xinjiang from July 1, 2009 to June 30, 2015 were col-lected from Chinese CDC Infectious Disease Reporting Information Management System ( reporting system ) . On-site epidemiological investigation was conducted in October, 2014, among children under 3 years in 23 villages in Gholtoghrak Township and Koxawat Township in Jiashi County, regions that had dramatically increased reports of VL cases from July 1. For suspected cases who showed symptoms such as fever and hepato-splenomegaly, blood (20 μl) was collected through fingerstick (with parental guardian consent) for rk39 immunochromatographic strip testing. Chil-dren with positive results were given sodium stibogluconate treatment (6×200 mg/kg, intravenously). Results A total of 637 VL cases were reported in Xinjiang from July 1, 2009 to June 30, 2015. Among the 192 cases reported from July 1, 2014 to June 30, 2015 in Xinjiang, cases from Jiashi County occupied 86.46% (166/192) of the cases. The number of VL cases in Jiashi County showed a trend of increase since the first report in August, with a total number of 114 in October, November and December. The 166 cases in Jiashi County had an age range of 23 days-8 years, with those under one year accounting for 95.18%(158/166). The 113 cases in Gholtoghrak Township of the County had an age range of 23 days-3 years, with those under one year accounting for 96.46% (109/113). The age-distribution of VL casess in the County accorded with the characteristic of the desert type. On-site investi-gation of 833 children in the 23 villiages revealed 11 children with positive results of rk39 immunochromatographic strip testing out of 14 suspected cases, all recovered after one course of sodium stibogluconate treatment. Conclu-sion In 2014, VL outbreak occurs in Jiashi County with 95% of

  20. [Feline leishmaniasis: what's the epidemiological role of the cat?].

    Mancianti, F

    2004-06-01

    . Visceral leishmaniasis is not common in cats: this form shows visceral involvement: liver and spleen are interested, with lymph nodes and kidney. The cat probably has to considerate to play an active role in the disease, in contrast to goats, calves and horses who could act as accidental reservoirs of leishmania, while sheep appears to be not susceptible to experimental infection. In endemic foci for kala-azar in Sudan cows, goats and donkeys had a high prevalence of specific antibodies. Recently in Europe sporadic cases of equine leishmaniasis have been reported: L. infantum was the causative agent. Equine leishmaniasis appears as a self-healing skin-dwelling disease, with a massive accumulation of parasites. The animals do not often show detectable specific antibodies and recover without any chemotherapy. Untreated affected cats can frequently die and we also observed lymph nodes and blood involvement indicating a spread of leishmania in feline hosts. The epidemiological role of the cat has never been clarified due also to lack of xenodiagnosis trials. This species is believed to have a high degree of natural resistance, as observed following experimental infection. Some of the affected cats were FIV and/or FeLV positive and these viroses such as stress may induce an impaired cellular immune response, even if leishmania infected cat was not submitted to CD4+, CD8+ lymphocyte counts nor other immunological test. However the resistance of the cat to leishmania infection probably depends on genetic factors, not strictly related to cell mediated immunity, taking into account the high seroprevalence of FIV infections (30%) in our country versus the number of clinical cases. PMID:15305717

  1. Hourly activity of Lutzomyia neivai in the endemic zone of cutaneous leishmaniasis in Tucumán, Argentina: preliminary results

    Ana Denise Fuenzalida

    2011-08-01

    Full Text Available In the present work, the hourly activity of Lutzomyia neivai was studied in the southern part of the province of Tucumán, Argentina, in an area of transmission of cutaneous leishmaniasis during two months of higher activity. In addition, the variables that influenced the abundance of Lu. neivai were evaluated. A total of 1,146 individuals belonging to Lu. neivai (97% and Lutzomyia migonei (3% were captured. The hourly activity of Lu. neivai was mainly nocturnal, with a bimodal pattern in both months. In January, the variable that most influenced the abundance of Lu. neivai was the temperature, whereas in April, that variable was humidity. These results may contribute to the design of anti-vectorial control measures at a micro-focal scale.

  2. Intracolonical administration of protease-activated receptor-2 agonists produced visceral hyperalgesia by up-regulating serotonin in the colon of rats.

    Li, Zhi; Zhang, Xiao-Jun; Xu, Hong-xi; Sung, Joseph J Y; Bian, Zhao-xiang

    2009-03-15

    This study aimed to investigate the underlying mechanism of protease-activated receptor-2 (PAR-2) agonist-induced visceral hyperalgesia. Male Sprague-Dawley rat pups were submitted to colonic injection of PAR-2 agonist for 6 consecutive days. The visceral sensitivity to colorectal distention was evaluated by electromyography. The enterochromaffin (EC) cell number, 5-HT content and tryrptophan hydroxylase (TPH) protein expression were detected with immunohistochemistry, fluorescent measurement and Western blot analysis. PAR-2 agonist induced a significant increase of visceral nociceptive response to colorectal distention and a series of neurochemical changes in rat colon, including proliferation of EC cells, increased 5-HT content and enhanced TPH expression. Expression of PAR-2 in EC cells was reported for the first time. Further, selective 5-HT(3) receptor antagonist alosteron significantly inhibited PAR-2-induced visceral hyperalgesia. The enhanced 5-HT signaling is likely responsible for the visceral hyperalgesia induced by PAR-2 agonist. Interruption of this pathway is a possible target for the treatment of visceral hyperalgesia in gastrointestinal diseases. PMID:19374846

  3. Cross-protective effect of a combined L5 plus L3 Leishmania major ribosomal protein based vaccine combined with a Th1 adjuvant in murine cutaneous and visceral leishmaniasis

    Ramírez, Laura; Corvo, Laura; Duarte, Mariana C; Miguel A Chávez-Fumagalli; Diogo G Valadares; Santos, Diego M.; de Oliveira, Camila I.; Escutia, Marta R; Alonso, Carlos; Bonay, Pedro; Carlos A. P. Tavares; Coelho, Eduardo A. F.; Soto, Manuel

    2014-01-01

    Abstract Background Two Leishmania major ribosomal proteins L3 (LmL3) and L5 (LmL5) have been described as protective molecules against cutaneous leishmaniasis due to infection with L. major and Leishmania braziliensis in BALB/c mice when immunized with a Th1 adjuvant (non-methylated CpG-oligodeoxynucleotides; CpG-ODN). In the present study we analyzed the cross-protective efficacy of an LmL3-LmL5-CpG ODN combined vaccine against infection with Leishmania amazonensis and Leishmania chagasi (s...

  4. Performance of an ELISA and Indirect Immunofluorescence Assay in Serological Diagnosis of Zoonotic Cutaneous Leishmaniasis in Iran

    Bahador Sarkari; Marzieh Ashrafmansouri; GholamReza Hatam; Parvaneh Habibi; Samaneh Abdolahi Khabisi

    2014-01-01

    Serological assays have been extensively evaluated for diagnosis of visceral leishmaniasis (VL) and considered as a routine method for diagnosis of VL while these methods are not properly evaluated for diagnosis of cutaneous leishmaniasis (CL). This study aimed to assess the performance of indirect immunofluorescent-antibody test (IFA) and enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of cutaneous leishmaniasis in Iran. Sixty-one sera samples from parasitologically confirmed CL ...

  5. Indirect immunofluorescence test in new world Leishmaniasis: serological and clinical relation-ship

    Sergio C. F. Mendonça

    1988-09-01

    Full Text Available The indirect immunofluorescence test (IF for anti-Leishmania antibodies (IgC and IgM was performed with sera form the following groups of individuals: 214 cutaneous leishmaniasis patients, 28 healthy subjects with positive Montenegro's skin test (MST, 29 healthy subjects with negativeMST and 16 visceral leishmaniasis patients. The first four groups came from a suburban area of Rio de Janeiro (Jacarepaguá where cutaneous leishmaniasis caused by Leishmania braziliensis braziliensis is endemic. It was observed that IF-IgM titers were significantly higher amongst the cutaneous leishmaniasis patients with less than four months of disease as compared to those with longer periods and that IF-IgG titers were significantly higher in patients with multiple lesions as compared to those with single lesions. The visceral leishmaniasis patients had IF-IgG titers significantly higher than those from cutaneous leishmaniasis patients. A group of 28 individuals selected amongst the 214 cutaneous leishmaniasis patients had their IF-titers (IgG and IgM compared to those of the two control groups of healthy subjects from the endemic area, respectively with positive and negative MST. Significantly higher titers of IF-IgG and IF-IgM were found in the group with active disease. The same group of patients showed IF-IgG titers significantly lower at the end of the antimonial therapy than those observed during this tratment.O teste de imunofluorescência indireta (IF para a detecção de anticorpos anti-Leismania nas classes IgG e IgM foi realizado em soros de indivíduos dos seguintes grupos: 214 pacientes com leismaniose cutânea, quatro pacientes com leismaniose mucocutânea, 28 indivíduos sadios com intradermorreação de Montenegro (IDRM positiva, 29 indivíduos sadios com IDRM negativa e 16 pacientes com leishmaniose visceral. Os indivíduos dos quatro primeiros grupos eram provenientes de uma área da periferia da cidade do Rio de Janeiro (Jacarepaguá onde a

  6. Mucocutaneous Leishmaniasis/HIV Coinfection Presented as a Diffuse Desquamative Rash

    Guilherme Almeida Rosa da Silva

    2014-01-01

    Full Text Available Leishmaniasis is an infectious disease that is endemic in tropical areas and in the Mediterranean. This condition spreads to 98 countries in four continents, surpassing 12 million infected individuals, with 350 million people at risk of infection. This disease is characterized by a wide spectrum of clinical syndromes, caused by protozoa of the genus Leishmania, with various animal reservoirs, such as rodents, dogs, wolves, foxes, and even humans. Transmission occurs through a vector, a sandfly of the genus Lutzomyia. There are three main clinical forms of leishmaniasis: visceral leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis. The wide spectrum of nonvisceral forms includes: localized cutaneous leishmaniasis, a papular lesion that progresses to ulceration with granular base and a large framed board; diffuse cutaneous leishmaniasis; mucocutaneous leishmaniasis, which can cause disfiguring and mutilating injuries of the nasal cavity, pharynx, and larynx. Leishmaniasis/HIV coinfection is considered an emerging problem in several countries, including Brazil, where, despite the growing number of cases, a problem of late diagnosis occurs. Clinically, the cases of leishmaniasis associated with HIV infection may demonstrate unusual aspects, such as extensive and destructive lesions. This study aims to report a case of mucocutaneous leishmaniasis/HIV coinfection with atypical presentation of diffuse desquamative eruption and nasopharyngeal involvement.

  7. Visceral Pain and Gastrointestinal Microbiome

    Chichlowski, Maciej; Rudolph, Colin

    2015-01-01

    A complex set of interactions between the microbiome, gut and brain modulate responses to visceral pain. These interactions occur at the level of the gastrointestinal mucosa, and via local neural, endocrine or immune activity; as well as by the production of factors transported through the circulatory system, like bacterial metabolites or hormones. Various psychological, infectious and other stressors can disrupt this harmonious relationship and alter both the microbiome and visceral pain res...

  8. Pink plaque on the arm of a man after a trip to Mexico: cutaneous leishmaniasis.

    Cohen, Jeffrey M; Saavedra, Arturo P; Sax, Paul E; Lipworth, Adam D

    2015-06-01

    Cutaneous leishmaniasis is a parasitic infection caused by protozoa of the Leishmania genus that presents as asymptomatic pink papules that may ulcerate. There are several species of Leishmania found in 98 endemic countries and whereas all are associated with cutaneous disease, only specific species can cause mucocutaneous or visceral disease. Although the diagnosis of cutaneous leishmaniasis can be confirmed with Giemsa staining of a biopsy or "touch prep" specimen, only speciation at specialized centers such as the Centers for Disease Control (CDC) can determine the risk of mucocutaneous or visceral disease. Treatment of cutaneous leishmaniasis is varied and depends on the extent of cutaneous disease and the risk of mucocutaneous or visceral disease. PMID:26158361

  9. Digestive enzyme activities are higher in the shortfin mako shark, Isurus oxyrinchus, than in ectothermic sharks as a result of visceral endothermy.

    Newton, Kyle C; Wraith, James; Dickson, Kathryn A

    2015-08-01

    Lamnid sharks are regionally endothermic fishes that maintain visceral temperatures elevated above the ambient water temperature. Visceral endothermy is thought to increase rates of digestion and food processing and allow thermal niche expansion. We tested the hypothesis that, at in vivo temperatures, the endothermic shortfin mako shark, Isurus oxyrinchus, has higher specific activities of three digestive enzymes-gastric pepsin and pancreatic trypsin and lipase-than the thresher shark, Alopias vulpinus, and the blue shark, Prionace glauca, neither of which can maintain elevated visceral temperatures. Homogenized stomach or pancreas tissue obtained from sharks collected by pelagic longline was incubated at both 15 and 25 °C, at saturating substrate concentrations, to quantify tissue enzymatic activity. The mako had significantly higher enzyme activities at 25 °C than did the thresher and blue sharks at 15 °C. This difference was not a simple temperature effect, because at 25 °C the mako had higher trypsin activity than the blue shark and higher activities for all enzymes than the thresher shark. We also hypothesized that the thermal coefficient, or Q 10 value, would be higher for the mako shark than for the thresher and blue sharks because of its more stable visceral temperature. However, the mako and thresher sharks had similar Q 10 values for all enzymes, perhaps because of their closer phylogenetic relationship. The higher in vivo digestive enzyme activities in the mako shark should result in higher rates of food processing and may represent a selective advantage of regional visceral endothermy. PMID:25893905

  10. Systematic Review into Diagnostics for Post-Kala-Azar Dermal Leishmaniasis (PKDL)

    Adams, Emily R.; Inge Versteeg; Leeflang, Mariska M. G.

    2013-01-01

    Identification of post-kala-azar dermal leishmaniasis (PKDL) is important due to the long and toxic treatment and the fact that PKDL patients may serve as a reservoir for visceral leishmaniasis (VL). We summarized the published literature about the accuracy of diagnostic tests for PKDL. We searched Medline for eligible studies investigating the diagnostic accuracy of any test for PKDL. Study quality was assessed using QUADAS-2. Data were extracted from 21 articles including 43 separate studie...

  11. Pink plaque on the arm of a man after a trip to Mexico: cutaneous leishmaniasis

    Cohen, Jeffrey M.; Saavedra, Arturo P; Sax, Paul E.; Lipworth, Adam D

    2015-01-01

    Cutaneous leishmaniasis is a parasitic infection caused by protozoa of the Leishmania genus that presents as asymptomatic pink papules that may ulcerate. There are several species of Leishmania found in 98 endemic countries and whereas all are associated with cutaneous disease, only specific species can cause mucocutaneous or visceral disease. Although the diagnosis of cutaneous leishmaniasis can be confirmed with Giemsa staining of a biopsy or “touch prep” specimen, only speciation at specia...

  12. Consultation meeting on the development of therapeutic vaccines for post kala azar dermal leishmaniasis

    Ghalib, Hashim; Modabber, Farrokh

    2007-01-01

    Background Post kala azar dermal leishmaniasis (PKDL) is a disease that appears after treatment of visceral leishmaniasis (VL). The highest incidence of PKDL in the world is in Sudan. Many patients heal spontaneously within 6 months but those who don't are difficult to treat, often requiring months of daily injections. These patients harbour parasite in their skin and are believed to be a source of infection and possibly epidemics. Present treatment modalities of PKDL are inadequate and impra...

  13. Factors Associated with the Seroprevalence of Leishmaniasis in Dogs Living around Atlantic Forest Fragments

    Curi, Nelson Henrique de Almeida; Paschoal, Ana Maria de Oliveira; Massara, Rodrigo Lima; Marcelino, Andreza Pain; Ribeiro, Adriana Aparecida; Passamani, Marcelo; Demétrio, Guilherme Ramos; Chiarello, Adriano Garcia

    2014-01-01

    Canine visceral leishmaniasis is an important zoonosis in Brazil. However, infection patterns are unknown in some scenarios such as rural settlements around Atlantic Forest fragments. Additionally, controversy remains over risk factors, and most identified patterns of infection in dogs have been found in urban areas. We conducted a cross-sectional epidemiological survey to assess the prevalence of leishmaniasis in dogs through three different serological tests, and interviews with owners to a...

  14. Successful Miltefosine Treatment of Post-Kala-Azar Dermal Leishmaniasis Occurring During Antiretroviral Therapy.

    Belay, A Dejenie; Asafa, Y; Mesure, J; Davidson, R. N.

    2006-01-01

    The first two patients to be treated with miltefosine for post-kala-azar dermal leishmaniasis (PKDL) are reported. One was a 26-year-old Ethiopian man who had been treated with sodium stibogluconate, for relapsing visceral leishmaniasis (VL), four times between August 2002 and March 2004. In January 2004 this patient was found to be seropositive for HIV and began antiretroviral treatment with stavudine, lamivudine and nevirapine. Five months later he developed clinical PKDL, with extensive cu...

  15. Status of vaccine research and development of vaccines for leishmaniasis.

    Gillespie, Portia M; Beaumier, Coreen M; Strych, Ulrich; Hayward, Tara; Hotez, Peter J; Bottazzi, Maria Elena

    2016-06-01

    A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous leishmaniasis (CL) is a disfiguring NTD highly endemic in the Middle East, Central Asia, North Africa, and the Americas. Estimates attribute 50,000 annual deaths and 3.3 million disability-adjusted life years to leishmaniasis. There are only a few approved drug treatments, no prophylactic drug and no vaccine. Ideally, an effective vaccine against leishmaniasis will elicit long-lasting immunity and protect broadly against VL and CL. Vaccines such as Leish-F1, F2 and F3, developed at IDRI and designed based on selected Leishmania antigen epitopes, have been in clinical trials. Other groups, including the Sabin Vaccine Institute in collaboration with the National Institutes of Health are investigating recombinant Leishmania antigens in combination with selected sand fly salivary gland antigens in order to augment host immunity. To date, both VL and CL vaccines have been shown to be cost-effective in economic modeling studies. PMID:26973063

  16. Visceral adiposity syndrome.

    Lopes, Heno F; Corrêa-Giannella, Maria Lúcia; Consolim-Colombo, Fernanda M; Egan, Brent M

    2016-01-01

    adipose tissue blocks lipolysis to a variety of lipolytic stimuli and adipose tissue send inputs to the brain. An imbalance of sympathetic/parasympathetic and alpha2 adrenergic/beta3 receptor is related to visceral adipose tissue storage and insulin sensitivity. Thus, in addition to the well-known factors classically associated with VAS, abnormal autonomic activity also emerges as an important factor regulating white adipose tissue, which highlights complex role of adipose tissue in the VAS. PMID:27437032

  17. Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder

    Lai, H. Henry; Qiu, Chang-Shen; Crock, Lara W.; Morales, Maria Elena P.; Ness, Tim J.; Gereau, Robert W.

    2011-01-01

    Activation of extracellular signal-regulated kinases (ERK) 1/2 in dorsal horn neurons is important for the development of somatic hypersensitivity and spinal central sensitization after peripheral inflammation. However, data regarding the roles of spinal ERK1/2 in the development of visceral hyperalgesia are sparse. Here we studied the activation of ERK1/2 in the lumbosacral spinal cord following innocuous and noxious distention of the inflamed (cyclophosphamide- treated) and non-inflamed uri...

  18. Molecular epidemiology of imported cases of leishmaniasis in Australia from 2008 to 2014.

    Roberts, Tamalee; Barratt, Joel; Sandaradura, Indy; Lee, Rogan; Harkness, John; Marriott, Deborah; Ellis, John; Stark, Damien

    2015-01-01

    Leishmaniasis is a vector borne disease caused by protozoa of the genus Leishmania. Human leishmaniasis is not endemic in Australia though imported cases are regularly encountered. This study aimed to provide an update on the molecular epidemiology of imported leishmaniasis in Australia. Of a total of 206 biopsies and bone marrow specimens submitted to St Vincent's Hospital Sydney for leishmaniasis diagnosis by PCR, 55 were found to be positive for Leishmania DNA. All PCR products were subjected to restriction fragment length polymorphism analysis for identification of the causative species. Five Leishmania species/species complexes were identified with Leishmania tropica being the most common (30/55). Travel or prior residence in a Leishmania endemic region was the most common route of acquisition with ~47% of patients having lived in or travelled to Afghanistan. Cutaneous leishmaniasis was the most common manifestation (94%) with only 3 cases of visceral leishmaniasis and no cases of mucocutaneous leishmaniasis encountered. This report indicates that imported leishmaniasis is becoming increasingly common in Australia due to an increase in global travel and immigration. As such, Australian clinicians must be made aware of this trend and consider leishmaniasis in patients with suspicious symptoms and a history of travel in endemic areas. This study also discusses the recent identification of a unique Leishmania species found in native kangaroos and a potential vector host which could create the opportunity for the establishment of a local transmission cycle within humans. PMID:25734905

  19. One Health: The global challenge of epidemic and endemic leishmaniasis

    Day Michael J

    2011-10-01

    Full Text Available Abstract 'One Health' proposes the unification of medical and veterinary sciences with the establishment of collaborative ventures in clinical care, surveillance and control of cross-species disease, education, and research into disease pathogenesis, diagnosis, therapy and vaccination. The concept encompasses the human population, domestic animals and wildlife, and the impact that environmental changes ('environmental health' such as global warming will have on these populations. Visceral leishmaniasis is a perfect example of a small companion animal disease for which prevention and control might abolish or decrease the suffering of canine and human patients, and which aligns well with the One Health approach. In this review we discuss how surveillance for leishmaniases is undertaken globally through the control of anthroponootic visceral leishmaniasis (AVL and zoonotic visceral leishmaniasis (ZVL. The ZVL epidemic has been managed to date by the culling of infected dogs, treatment of human cases and control of the sandfly vector by insecticidal treatment of human homes and the canine reservoir. Recently, preventive vaccination of dogs in Brazil has led to reduction in the incidence of the canine and human disease. Vaccination permits greater dog owner compliance with control measures than a culling programme. Another advance in disease control in Africa is provided by a surveillance programme that combines remote satellite sensing, ecological modelling, vector surveillance and geo-spatial mapping of the distribution of vectors and of the animal-to-animal or animal-to-human pathogen transmission. This coordinated programme generates advisory notices and alerts on emerging infectious disease outbreaks that may impede or avoid the spreading of visceral leishmaniasis to new areas of the planet as a consequence of global warming.

  20. Primary oral leishmaniasis mimicking oral cancer: a case report.

    Celentano, A; Ruoppo, E; Mansueto, G; Mignogna, M D

    2015-04-01

    Primary mucosal leishmaniasis is a rare infectious disease, particularly in immunocompetent patients. We present a 50-year-old patient with a 6-week history of a painful lesion of the left buccal mucosa that mimicked cancer. The exophytic lesion looked invasive, and we took an incisional biopsy specimen to exclude cancer. The diagnosis of leishmaniasis was unexpected, and the patient was successfully treated with amphotericin B for five weeks. After five months the patient had a visceral recurrence. Chronic exophytic and ulcerated mucosal lesions that do not heal within 3-4 weeks should be regarded as the first signs of oral cancer, but primary oral leishmaniasis can easily mimic it. PMID:25701438

  1. Salivary gland transcriptomes and proteomes of Phlebotomus tobbi and Phlebotomus sergenti, vectors of leishmaniasis.

    Iva Rohoušová

    Full Text Available BACKGROUND: Phlebotomus tobbi is a vector of Leishmania infantum, and P. sergenti is a vector of Leishmania tropica. Le. infantum and Le. tropica typically cause visceral or cutaneous leishmaniasis, respectively, but Le. infantum strains transmitted by P. tobbi can cause cutaneous disease. To better understand the components and possible implications of sand fly saliva in leishmaniasis, the transcriptomes of the salivary glands (SGs of these two sand fly species were sequenced, characterized and compared. METHODOLOGY/PRINCIPAL FINDINGS: cDNA libraries of P. tobbi and P. sergenti female SGs were constructed, sequenced, and analyzed. Clones (1,152 were randomly picked from each library, producing 1,142 high-quality sequences from P. tobbi and 1,090 from P. sergenti. The most abundant, secreted putative proteins were categorized as antigen 5-related proteins, apyrases, hyaluronidases, D7-related and PpSP15-like proteins, ParSP25-like proteins, PpSP32-like proteins, yellow-related proteins, the 33-kDa salivary proteins, and the 41.9-kDa superfamily of proteins. Phylogenetic analyses and multiple sequence alignments of putative proteins were used to elucidate molecular evolution and describe conserved domains, active sites, and catalytic residues. Proteomic analyses of P. tobbi and P. sergenti SGs were used to confirm the identification of 35 full-length sequences (18 in P. tobbi and 17 in P. sergenti. To bridge transcriptomics with biology P. tobbi antigens, glycoproteins, and hyaluronidase activity was characterized. CONCLUSIONS: This analysis of P. sergenti is the first description of the subgenus Paraphlebotomus salivary components. The investigation of the subgenus Larroussius sand fly P. tobbi expands the repertoire of salivary proteins in vectors of Le. infantum. Although P. tobbi transmits a cutaneous form of leishmaniasis, its salivary proteins are most similar to other Larroussius subgenus species transmitting visceral leishmaniasis. These

  2. Association of visceral adiposity with increased intrarenal artery resistive index in HIV-1-infected patients receiving highly active antiretroviral therapy

    Grima Pierfrancesco

    2010-01-01

    Full Text Available Purpose: The aim of our study was to evaluate whether perirenal fat thickness (PRFT, a parameter of central obesity, is related to kidney function and intrarenal artery resistive index (IARI in human immunodeficiency virus (HIV-1-infected patients. Materials and Methods: We enrolled 102 consecutive HIV-1-infected patients receiving highly active antiretroviral therapy for more than 12 months in a prospective cohort study. Echographically, the PRFT and IARI were measured and the serum metabolic parameters were evaluated. PRFT and IARI were measured using a 3.75 MHz convex linear probe. Results: The mean of PRFT and IARI in HIV-1-infected patients with visceral obesity was considerably higher than that in patients without it (P <0.001 and <0.01, respectively. Using the average IARI as the dependent variable, age (odds ratio, 1.07; 95% confidence interval [CI], 1.01-1.14; P < 0.5 and PRFT (odds ratio, 1.28; 95% CI, 1.08-1.51; P<0.01 were independent factors associated with IARI. Conclusion: Our data indicate that ultrasonographic assessment of PRFT may have a potential to be a marker of increased endothelial damage with specific involvement of the renal vascular district in HIV-1-infected patients.

  3. Leishmaniasis and AIDS coinfection*

    Hozannah, Adriana; Santos, Monica; Chrusciak-Talhari, Anette; Talhari, Carolina

    2013-01-01

    Cutaneous leishmaniasis and HIV coinfection has been reported in Brazil since the initial description of AIDS in the country. We report an HIV-positive patient under antiretroviral treatment who presented with cutaneous leishmaniasis which was successfully treated with meglumine antimoniate.

  4. Comparison of the immune profile of nonhealing cutaneous Leishmaniasis patients with those with active lesions and those who have recovered from infection

    Ajdary, S; Alimohammadian, M H; Eslami, M B;

    2000-01-01

    Th1-type cellular immune responses play a critical role in protection against infection with Leishmania parasites, whereas activation of Th2-type cells results in progressive disease. Cutaneous leishmaniasis caused by Leishmania major is often a self-healing disease; however, persistent nonhealing...... significantly lower and showed a Th2-type response to Leishmania antigens. Interleukin-10 (IL-10) production was not a feature of L. major stimulation. Flow cytometric analysis revealed that L. major antigen induced proliferation of the CD4-positive population and that these cells were the major source of gamma...

  5. Modulation of visceral pain and inflammation by protease-activated receptors

    Vergnolle, Nathalie

    2004-01-01

    The gastrointestinal (GI) tract is exposed to a large array of proteases, under both physiological and pathophysiological conditions. The discovery of G protein-coupled receptors activated by proteases, the protease-activated receptors (PARs), has highlighted new signaling functions for proteases in the GI tract, particularly in the domains of inflammation and pain mechanisms. Activation of PARs by selective peptidic agonists in the intestine or the pancreas leads to inflammatory events and c...

  6. 我国内脏利什曼病不同疫区病原体小亚基核糖体DNA可变区序列差异%Difference in DNA sequences in SSU rDNA variable regions among pathogens isola ted from different epidemic foci of visceral leishmaniasis in China

    胡孝素; 卜玲毅; 马莹; 王雅静; 敬保迁; 易桃林

    2002-01-01

    目的 试验证实我国黑热病不同疫区分离出的5个L.d分离株的小亚基核糖体DNA可变区序列存在点突变.方法将7个利什曼原虫种/株的nDNA进行PCR扩增,将扩增出的SSU rDNA基因的特异片段克隆于pGEMR-T Easy Vector上,采用通用引物M13进行PCR扩增,全自动测序仪测序。结果序列分析显示,扩增的7种/株利什曼原虫SSU rDNA序列大小为392 bp,5个点突变均发生在两个独特序列区(UQ-I和UQ-II);无移码突变。经与基因库中利什曼原虫序列类似性比较,同源性在98%以上。结论首次报道我国黑热病不同疫区的5个L.d.分离株的SSU rDNA可变区存在5个点突变。%Objective To confirm the existence of point mutations I n the SSU rDNA variable regions of 5 Leishmania donovani (L-d) isolates from different epidemic foci in ChinaMethods Specific SSU rDNA fragments from nuclear DNA of 7 Leishmania species/isolates were amplified by PCR and then cloned into pGEMR-T Easy Vectors After that, the specific fragments were sequenced by an auto mated DNA sequencerResults Sequence analysis showed that the amplified DNA fragments of 7 Leishmania species/isolates were all 392 bp in length All 5 po int mutations were located in two unique sequence blocks (UQ-Ⅰ and UQ-Ⅱ), a nd no insertions or deletions were found The dentities of comparison of Leish mania in GeneBank were more than 98%.Conclusion Five point mutations exist in the ssu rDNA variable region of 5 L.d.isolates from different epidemic foci of visceral leishmaniasis (VL) in China. Sequence differences differences of the SSU rDNA variable region exist among L.d.isolates from different foci.

  7. Activation of human T lymphocytes by Leishmania lipophosphoglycan

    Kemp, M; Theander, T G; Handman, E;

    1991-01-01

    This study describes Leishmania antigen-induced activation of lymphocytes isolated from Kenyan donors, previously treated for visceral leishmaniasis, and from Danish and Kenyan controls. Peripheral blood mononuclear cells (PBMC) from cured Kala-Azar patients proliferated and produced Interferon......-gamma in vitro in response to lipophosphoglycan (LPG) isolated from Leishmania major. The proliferative response was mainly due to activation of CD2-positive T cells. PBMC from controls did not respond to LPG, but to sonicates prepared from both L. major and L. donovani promastigotes. The surface glycoprotein GP...... 63 failed to activate PBMC from any of the donors tested. These results show that the individuals cured from visceral leishmaniasis had expanded T-cell clones recognizing LPG, conceivably as a result of Leishmania infection. The LPG preparation was without detectable protein contamination. Thus...

  8. [Cutaneous leishmaniasis as travelers' disease. Clinical presentation, diagnostics and therapy].

    von Stebut, E; Schleicher, U; Bogdan, C

    2012-03-01

    Leishmaniasis is a disease with worldwide increasing incidence, which in Germany is almost exclusively observed in patients who have travelled to classical endemic regions such as the Mediterranean basin. Cause of the disease is an infection with protozoan parasites of the genus Leishmania, which are transmitted by sand flies and replicate intracellularly within mammalian hosts. Depending on the inoculated parasite (sub-) species and the immune status of the host, a local cutaneous, diffuse cutaneous, mucocutaneous or visceral form of leishmaniasis will develop. Cutaneous leishmaniasis, which frequently appears only weeks after the bite of a sand fly, starts with the formation of a papule, which subsequently can turn into a skin ulcer. The latter may heal spontaneously after months leaving behind a scar or persist as chronic, non-healing cutaneous leishmaniasis. If cutaneous leishmaniasis is suspected, a sterile skin biopsy followed by appropriate diagnostic measures in a specialized laboratory to identify the pathogen should be performed. For the decision on the type of therapy, several clinical parameters (e.g. number and localization of lesions, immune status) and, most importantly, the underlying parasite (sub-) species need to be considered. Therapy can consist of a variety of topical measures or systemic drug treatment. A modern and safe vaccine does not yet exist. PMID:22422121

  9. A century of leishmaniasis in Alpes-Maritimes, France.

    Marty, P; Izri, A; Ozon, C; Haas, P; Rosenthal, E; Del Giudice, P; Godenir, J; Coulibaly, E; Gari-Toussaint, M; Delaunay, P; Ferrua, B; Haas, H; Pratlong, F; Le Fichoux, Y

    2007-10-01

    A century of publications on leishmaniasis in Alpes-Maritimes, in southern France, is here reviewed. Autochtonous human and canine leishmaniasis were first recognised in this département, which lies by the Mediterranean Sea and near the Italian border, in 1918 and 1925, respectively. The parasite responsible for the leishmaniasis, Leishmania infantum, is transmitted by Phlebotomus perniciosus and P. ariasi. The human leishmaniasis is zoonotic, with domestic dogs acting as the main 'reservoir' hosts. In prospective surveys over the last two decades, a mean of 12% of the domestic dogs checked in Alpes-Maritimes have been found seropositive for L. infantum but only about 50% of the seropositive animals showed any clinical signs of infection at the time of the surveys. During the last 30 years, 178 cases of human visceral leishmaniasis have been recorded in the area. Such cases are sporadic and often opportunistic, occurring predominantly in children (29% of the 178 cases) or HIV-positive subjects (31%). Recently, it has been demonstrated that, in Alpes-Maritimes, approximately 20% of those found seropositive in leishmanin skin tests are asymptomatic carriers, with amastigotes in their peripheral blood. PMID:17877875

  10. Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity

    Kwon Eun-Young

    2012-09-01

    Full Text Available Abstract Background Visceral white adipose tissue (WAT hypertrophy, adipokine production, inflammation and fibrosis are strongly associated with obesity, but the time-course of these changes in-vivo are not fully understood. Therefore, the aim of this study was to establish the time-course of changes in adipocyte morphology, adipokines and the global transcriptional landscape in visceral WAT during the development of diet-induced obesity. Results C57BL/6 J mice were fed a high-fat diet (HFD or normal diet (ND and sacrificed at 8 time-points over 24 weeks. Excessive fat accumulation was evident in visceral WAT depots (Epidydimal, Perirenal, Retroperitoneum, Mesentery after 2–4 weeks. Fibrillar collagen accumulation was evident in epidydimal adipocytes at 24 weeks. Plasma adipokines, leptin, resistin and adipsin, increased early and time-dependently, while adiponectin decreased late after 20 weeks. Only plasma leptin and adiponectin levels were associated with their respective mRNA levels in visceral WAT. Time-course microarrays revealed early and sustained activation of the immune transcriptome in epididymal and mesenteric depots. Up-regulated inflammatory genes included pro-inflammatory cytokines, chemokines (Tnf, Il1rn, Saa3, Emr1, Adam8, Itgam, Ccl2, 3, 4, 6, 7 and 9 and their upstream signalling pathway genes (multiple Toll-like receptors, Irf5 and Cd14. Early changes also occurred in fibrosis, extracellular matrix, collagen and cathepsin related-genes, but histological fibrosis was only visible in the later stages. Conclusions In diet-induced obesity, early activation of TLR-mediated inflammatory signalling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches

  11. [Penile sporotrichoid cutaneous leishmaniasis].

    Masmoudi, A; Boudaya, S; Bouzid, L; Frigui, F; Meziou, T J; Akrout, F; Turki, H; Zahaf, A

    2005-12-01

    The localisation of the cutaneous leishmaniasis of L. major at the penis level is rare, we report here a new observation. Mr K. R aged of 41, without known pathological background presented for 20 days a nodular lesion of the anterior face of the neck, 2 juxtaposed ulcerated nodular lesions of the left wrist. He presented also subcutaneous nodules ranged linearly and extended to the root of the penis. Theses lesions were covered by an erythematous or ulcerated skin. The smear made from the genital lesions of the penis confirmed the diagnosis of a cutaneous leishmaniasis. The evolution was favourable after a 21 days treatment by doxycyclin after an interval of one week. Our observation was specific by the localisation of the cutaneous leishmaniasis and by the clinical form. This shows that in our region cutaneous leishmaniasis is characterised by different clinical symptoms. PMID:16425718

  12. Evaluation of the in vivo leishmanicidal activity of amphotericin B emulgel: An alternative for the treatment of skin leishmaniasis.

    Pinheiro, Iluska Martins; Carvalho, Ivana Pereira; de Carvalho, Camila Ernanda Sousa; Brito, Lucas Moreira; da Silva, Andrezza Braga Soares; Conde Júnior, Airton Mendes; de Carvalho, Fernando Aécio Amorim; Carvalho, André Luis Menezes

    2016-05-01

    The American Cutaneous Leishmaniasis (ACL) is an infectious disease that can be fatal. The first line of treatment is pentavalent antimonies. However, due to its potential to develop resistance, Amphotericin B (AmB) started to be used as an alternative medicine. Current treatments are limited, a fact that has led to a growing interesting in developing new therapies. This study aims to evaluate the therapeutic potential in vivo of an amphotericin B + oleic acid (OA) emulgel in the treatment of cutaneous leishmaniasis in an experimental model. Strains of Leishmania major MHOM/IL/80/Friendlin of Leishmania major were used. The animals were inoculated subcutaneously. After the development of leishmanial, nodular or ulcerative lesions, the animals were divided into three groups (control, Group A and Group B) and treated twice a day for twelve days. The weight of the animals was measured and the size of the lesions was observed. A histopathological analysis was performed with skin fragments of lesions and with the spleen of animals treated with different treatments (emulgel, AmB 3% emulgel and AmB 3% plus OA 5% emulgel). It was observed that when subjected to treatment with AmB 3% emulgel during the study period using both formulations, with enhancer and without enhancer, ulcerative lesions regress gradually or even complete cure. The quantification of the average number of parasites recovered from the inoculation site was made after the treatment in each group and the differences were considered significant. The treatment with AmB 3% and OA 5% emulgel had the best in vivo therapeutic response, showing good prospects for cutaneous leishmaniasis therapy as an alternative therapy. PMID:26902606

  13. Análise Espacial da Leishmaniose Visceral Americana no Município de Presidente Prudente: Abordagem Geográfica da Saúde Ambiental | Spatial Analysis of American Visceral Leishmaniasis in the Municipality of Presidente Prudente: A Geographical Approach to E

    Patricia Sayuri Silvestre Matsumoto

    2014-05-01

    Full Text Available Normal 0 21 false false false PT-BR X-NONE X-NONE Introdução: A Leishmaniose Visceral Americana (LVA é uma zoonose grave. Atinge animais e homens e pode ser fatal. A mortalidade acentuada se dá, sobretudo, devido às condições de precariedade de diagnóstico e tratamento da doença e, por isso, é caracterizada como doença negligenciada. Desde 1990 a LVA vem se disseminando para novas áreas e aumentando sua frequência no estado de São Paulo. Em Presidente Prudente, município do oeste paulista, a enfermidade apareceu em meados de 2009 e vem se espalhando rapidamente entre a população canina, o que tem sido condição prévia para que haja a ocorrência em casos humanos. Pensando na problemática da LVA neste município, a proposta desta pesquisa é analisar a distribuição espacial dos casos de LVA caninos, identificando padrões espaciais da doença. Sabendo onde houve a confirmação de casos de LVA, também se pretende analisar o seu entorno, através de correlações da doença com o ambiente. Metodologia/Desenvolvimento: Para a análise da distribuição espacial dos casos de LVA canina no município de Presidente Prudente foi gerado um banco de dados georreferenciado. O mapeamento se deu por meio da ferramenta de geocodificação de endereços, que consiste em associar o banco de dados (tabela que se quer mapear ao banco de dados de vias por endereço já previamente georreferenciada. A ferramenta faz associações através de comparação de endereços e marca os pontos nas ruas conforme a localização do evento pontual. Após a espacialização dos dados, pretende-se aplicar técnicas em análise espacial, de modo a identificar padrões da doença no município. Também se pretende aplicar geoestatística no censo canino que está sendo cadastrado. Após o mapeamento e a identificação dos locais afetados com LVA, será feito um levantamento biogeográfico, com a intenção de encontrar correlações ambientais que

  14. Cutaneous leishmaniasis: a case report:

    Kokol, Rok; Marovt, Maruška; Miljković, Jovan; Stanimirović, Andrija

    2010-01-01

    Cutaneous leishmaniasis is the most common form of leishmaniasis caused by flagellate protozoa of the genus Leishmania transmitted by sand fly bites. OldWorld leishmaniasis is endemic in the Mediterranean Sea and the neighbouring countries. We present a case of a 10-year-old boy with a cutaneous leishmaniasis in form of papules on the nose, right and left lower leg. Histopathological examination showed diffuse dermal infiltrate predominantly of macrophages with admixture of few lymphocytes, e...

  15. Specificity of the rapid rK39 antigen-based immunochromatographic test Kalazar Detect(r in patients with cutaneous leishmaniasis in Brazil

    Felix Javier Leon Molinet

    2013-05-01

    Full Text Available The aim of this study was to evaluate the specificity of a rapid immunochromatographic test that was developed to detect antibodies against the rK39 antigen for the diagnosis of visceral leishmaniasis (VL. This evaluation was performed using sera from patients with a confirmed diagnosis of active cutaneous leishmaniasis. The sera from 272 patients with a confirmed diagnosis of localised cutaneous leishmaniasis (CL who resided in an area endemic for Leishmania braziliensis in Brazil were obtained before the initiation of antileishmanial treatment. Kalazar Detect(r(InBios, Seattle, WA recombinant K39 antigen-based immunochromatographic strips were used according to the manufacturer's instructions. The test results were evaluated independently by two examiners in sequential order. The positive controls for the test included five serum samples from five patients with parasitologically confirmed diagnosis of VL caused by Leishmania infantum in Brazil. Overall, 100% of the samples obtained from patients with CL were negative, confirming the absence of a serological cross-reaction for individuals with cutaneous disease when these patients were evaluated using the rapid test. The lack of a cross-reaction in patients who were infected by parasites of the same genus highlights the specificity of the rK39 antigen for the diagnosis of VL in areas with the sympatric circulation of L. braziliensis and L. infantum.

  16. Dichotomy of the T cell response to Leishmania antigens in patients suffering from cutaneous leishmaniasis; absence or scarcity of Th1 activity is associated with severe infections

    Gaafar, A; Kharazmi, A; Ismail, A;

    1995-01-01

    The T cell response was studied in 25 patients suffering from cutaneous leishmaniasis caused by Leishmania major with severe (n = 10) and mild (n = 15) disease manifestations. Peripheral blood mononuclear cells (PBMC) from the patients were activated by sonicates of Leishmania promastigotes (LMP......) and amastigotes (LDA), and the surface protease gp63. The proliferative responses to Leishmania antigens were lower in patients with severe disease than in patients with mild disease (P = 0.01-0.05), and such a difference was not observed in the response to purified protein derivative of tuberculin (PPD......) or tetanus toxoid (TT). LMP-induced interferon-gamma (IFN-gamma) production was lower in patients with severe than in patients with mild disease (P Leishmania...

  17. Identification of Leishmania spp. promastigotes in the intestines, ovaries and salivary glands of Rhipicephalus sanguineus actively infesting dogs

    Sand flies are recognized as the major vector of canine visceral leishmaniasis. However, in some areas of Brazil where sand flies do not occur, this disease is found in humans and dogs. There has been speculation that ticks might play a role in transmission of canine visceral leishmaniasis and the D...

  18. Polarity-sensitive nanocarrier for oral delivery of Sb(V) and treatment of cutaneous leishmaniasis

    Lanza, Juliane S; Fernandes, Flaviana R; Corrêa-Júnior, José D; Vilela, José MC; Magalhães-Paniago, Rogério; Ferreira, Lucas AM; Andrade, Margareth S; Demicheli, Cynthia; Melo, Maria N; Frézard, Frédéric

    2016-01-01

    There is a great need for orally active drugs for the treatment of the neglected tropical disease leishmaniasis. Amphiphilic Sb(V) complexes, such as 1:3 Sb–N-octanoyl-N-methylglucamide complex (SbL8), are promising drug candidates. It has been previously reported that SbL8 forms kinetically stabilized nanoassemblies in water and that this simple dispersion exhibits antileishmanial activity when given by oral route to a murine model of visceral leishmaniasis. The main objective of the present work was to interfere in the structural organization of these nanoassemblies so as to investigate their influence on the oral bioavailability of Sb, and ultimately, optimize an oral formulation of SbL8 for the treatment of cutaneous leishmaniasis. The structural organization of SbL8 nanoassemblies was manipulated through addition of propylene glycol (PG) to the aqueous dispersion of SbL8. The presence of 50% (v/v) PG resulted in the loss of hydrophobic microenvironment, as evidenced by fluorescence probing. However, nanostructures were still present, as demonstrated by dynamic light scattering, small-angle X-ray scattering, and atomic force microscopy (AFM). A remarkable property of these nanoassemblies, as revealed by AFM analysis, is the flexibility of their supramolecular organization, which showed changes as a function of the solvent and substrate polarities. The formulation of SbL8 in 1:1 water:PG given orally to mice promoted significantly higher and more sustained serum levels of Sb, when compared to SbL8 in water. The new formulation, when given as repeated doses (200 mg Sb/kg/day) to BALB/c mice infected with Leishmania amazonensis, was significantly more effective in reducing the lesion parasite burden, compared to SbL8 in water, and even, the conventional drug Glucantime® given intraperitoneally at the same dose. In conclusion, this work introduces a new concept of polarity-sensitive nanocarrier that was successfully applied to optimize an oral formulation of Sb

  19. Post-Kala-Azar Dermal Leishmaniasis: A Paradigm of Paradoxical Immune Reconstitution Syndrome in Non-HIV/AIDS Patients

    Eltahir Awad Gasim Khalil

    2013-01-01

    Full Text Available Visceral leishmaniasis (VL is a parasitic disease characterized by immune suppression. Successful treatment is usually followed by immune reconstitution and a dermatosis called post-Kala-azar dermal leishmaniasis (PKDL. Recently, PKDL was described as one of the immune reconstitution syndromes (IRISs in HIV/VL patients on HAART. This study aimed to present PKDL as a typical example of paradoxical IRIS in non-HIV/AIDS individuals. Published and new data on the pathogenesis and healing of PKDL was reviewed and presented. The data suggested that PKDL is a typical example of paradoxical IRIS, being a new disease entity that follows VL successful treatment and immune recovery. PKDL lesions are immune inflammatory in nature with granuloma, adequate response to immunochemotherapy, and an ensuing hypersensitivity reaction, the leishmanin skin test (LST. The data also suggested that the cytokine patterns of PKDL pathogenesis and healing are probably as follows: an active disease state dominated by IL-10 followed by spontaneous/treatment-induced IL-12 priming, IL-2 stimulation, and INF-γ production. INF-γ-activated macrophages eliminate the Leishmania parasites/antigen to be followed by LST conversion and healing. In conclusion, PKDL is a typical example of paradoxical IRIS in non-HIV/AIDS individuals with anti-inflammatory cytokine patterns that are superseded by treatment-induced proinflammatory cytokines and lesions healing.

  20. Epidemiology of Imported Leishmaniasis in Italy: Implications for a European Endemic Country.

    Di Muccio, Trentina; Scalone, Aldo; Bruno, Antonella; Marangi, Massimo; Grande, Romualdo; Armignacco, Orlando; Gradoni, Luigi; Gramiccia, Marina

    2015-01-01

    In the past decade, the number of imported leishmaniasis cases has increased in countries of Western Europe. The trend is associated with increasing travels, ecotourism activity, military operations and immigration. While in endemic countries leishmaniasis is usually well diagnosed, accurate patient history and parasite identification are necessary to distinguish between autochthonous and imported cases. This is particularly important, as new Leishmania species/genotypes may be introduced and transmitted by local phlebotomine vectors without appropriate surveillance, with unpredictable consequences. We report on the surveillance of imported leishmaniasis performed by the Leishmania Identification Reference Centre of Rome from 1986 through 2012, involving health care centres from 16/20 Italian regions. Suspected imported cases were analyzed and conclusions were based on clinical, epidemiological and diagnostic findings. Over the years, different parasite identification methods were employed, including MultiLocus Enzyme Electrophoresis and molecular techniques combining disease diagnosis (SSU rDNA nested-PCR) and Leishmania typing (nuclear repetitive sequence and ITS-1 PCR-RFLPs). A total of 105 imported cases were recorded (annual range: 0-20) of which 36 were visceral (VL) (16 HIV-coinfections) and 69 cutaneous (CL) cases; 85 cases (52 CL) were from the Old World and 20 (17 CL) from the New World. Eight Leishmania species were identified, of which 7 were exotic to Italy. VL importation until 1995 was associated with the spread of Mediterranean Leishmania-HIV co-infections in early 1990s. Following the introduction of HAART treatment, such cases became occasional in Italians but relatively frequent among immigrants. In contrast, a steady increase of CL cases was observed from different areas of the Old and New Worlds, that in recent years included mainly immigrants 'visiting friends and relatives' and Italian tourists. This positive trend likely depends on better

  1. Microscopic and Molecular Detection of Leishmania Species Among Suspected Patients of Cutaneous Leishmaniasis Using ITS-r DNA in Fars Province

    O Dehnam

    2012-10-01

    Full Text Available Introduction: Fars province is one of the most important foci of leishmaniasis that includes two types of cutaneous (urban and rural forms and visceral leishmaniasis in sympatry. To study leishmaniasis among suspected patients of cutaneous leishmaniasis in 5 counties of Shiraz, Firouz abad, GhirـKarzin, Farashband and Larestan, both microscopic and molecular analysis were carried out in the present study. Methods: The samples were smeared on the microscopic slides and were also stained by Giemsa. All smears were examined under a light microscope and the positive smears were scored for amastigote frequency. DNA was extracted from stained smears and Leishmania DNA was detected by amplification of ITS1ـ5.8sـITS2 fragments. Amplicons were analyzed using electrophoresis in 1.5 % agarose gel containing ethidium bromide. Results: Among 34 studied patients, 29 cases (%85 were positive in microscopic and 32 (%94 in molecular analysis using standard PCR. All examined samples were infected with L.major except one (%3 that was infected with L.tropica. Most lesions due to L.major were located on the feet, whereas ulcer due to L.tropica was on the forehead. Conclusions: Preparing stained smears from active lesions of suspected patients (microscopic analysis removes the problem of Leishmania preservation and transition to culture media. Also, intergenic variations in amplified fragment of ITS-rDNA cause to produce fragments with different length and based on this difference, we can identify L. major and L. tropica separately. Using microscopic and molecular methods in present study confirmed presence of L.major and L.tropica as the causative agents of CL in studied regions of Fars.

  2. Cutaneous Leishmaniasis, Sri Lanka

    Sujeevi S. K. Nawaratna; Weilgama, Danister J.; Wijekoon, Chandana J.; Dissanayake, Manel; Rajapaksha, Kosala

    2007-01-01

    Cutaneous leishmaniasis (CL) is an emerging disease in Sri Lanka. Of 116 patients with clinical symptoms suggestive of CL, 86 were confirmed positive for Leishmania donovani. Most patients had single dry lesions, usually on the face. Patients were from 5 of the 7 agroclimatic zones in Sri Lanka.

  3. Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats

    Ayyalasomayajula Vajreswari

    2011-06-01

    Full Text Available Abstract Background 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and its inhibition ameliorates obesity and metabolic syndrome. So far, no studies have reported the effect of dietary vitamin A on 11β-HSD1 activity in visceral fat and liver under normal and obese conditions. Here, we studied the effect of chronic feeding of vitamin A-enriched diet (129 mg/kg diet on 11β-HSD1 activity in liver and visceral fat of WNIN/Ob lean and obese rats. Methods Male, 5-month-old, lean and obese rats of WNIN/Ob strain (n = 16 for each phenotype were divided into two subgroups consisting of 8 rats of each phenotype. Control groups received stock diet containing 2.6 mg vitamin A/kg diet, where as experimental groups received diet containing 129 mg vitamin A/Kg diet for 20 weeks. Food and water were provided ad libitum. At the end of the experiment, tissues were collected and 11β-HSD1 activity was assayed in liver and visceral fat. Results Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα, the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα, a nuclear transcription factor which is known to downregulate 11β-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes. Conclusions This study suggests that chronic consumption of vitamin A-enriched diet decreases 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly

  4. Cutaneous leishmaniasis caused by Leishmania donovani in the tribal population of the Agasthyamala Biosphere Reserve forest, Western Ghats, Kerala, India.

    Kumar, N Pradeep; Srinivasan, R; Anish, T S; Nandakumar, G; Jambulingam, P

    2015-02-01

    Cutaneous leishmaniasis (CL), a neglected tropical disease, is reported to be prevalent in tribal villages located in the Agasthyamala Biosphere Reserve forests of Western Ghats, Kerala state, India. We carried out an investigation to characterize the species of Leishmania parasites involved in these infections prevalent among one of the oldest human tribal populations in India. Skin aspirates collected from 13 clinically diagnosed cases were subjected to histopathological investigations, serological rapid tests using 'rk39' and molecular diagnostics. Clinical manifestations recorded among the patients were hypo-pigmented erythematous nodules/papules on limbs and other parts of the body. Histopathological investigations of these skin lesions among patients showed Leishman-Donovan bodies in macrophages. None of the patients were found to be positive for rk39 tests, which detect active visceral leishmaniasis. Using three different genetic markers [kinetoplast minicircle DNA, 3' UTR region of heat-shock protein 70 (Hsp70) and Hsp70 gene] we identified the parasite species involved in these infections to be Leishmania donovani. The 6-phosphogluconate (6-PGDH) gene sequences of the parasite isolates from Western Ghats indicated close genetic relatedness to L. donovani isolates reported from Sri Lanka, also causing CL. This could be cited as another instance of 'local endemism' of organisms in this single 'bio-geographic unit'. PMID:25480880

  5. Current knowledge of sand fly fauna (Diptera: Psychodidae) of northwestern Yemen and how it relates to leishmaniasis transmission.

    El Sawaf, Bahira M; Kassem, Hala A; Mogalli, Nabil M; El Hossary, Shabaan S; Ramadan, Nadia F

    2016-10-01

    This report presents the results of the first entomological survey of the sand fly fauna in northwestern Yemen. Sand flies were collected using sticky paper traps and CDC light traps from Hajjah governorate, a cutaneous leishmaniasis focus due to Leishmania tropica. Six Phlebotomus species: P. alexandri, P. arabicus. P. bergeroti, P. orientalis, P. papatasi, P. sergenti and ten Sergentomyia species: S. africana, S. antennata, S. christophersi, S. dolichopa, S. dreyfussi, S. fallax, S. multidens, S. taizi, S. tiberiadis, S. yusafi were identified. P. alexandri was the most predominant Phlebotomus species and P. papatasi was a scarce species. S. fallax was the principal Sergentomyia species and S. dolichopa was the least species encountered. The diversity of the sand fly fauna within and among three altitudinal ranges using Simpson index and Jaccard's diversity coefficient respectively were measured. High species diversity was found in all altitude ranges. There seemed to be more association between sand fly fauna in higher altitudes with fauna from moderate altitudes. Sand fly seasonal activity showed a mono-modal trend in the lowland and a confluent bimodal trend in the highlands. Leishmania DNA could not be detected from 150 Phlebotomus females using PCR-RFLP. A possible zoonotic cutaneous transmission cycle due to Leishmania tropica in northwestern Yemen would involve P. arabicus as the sand fly vector and the rock hyrax as the reservoir host. The vector competence for P. alexandri as a vector of visceral leishmaniasis in Hajjah governorate is discussed. PMID:27282094

  6. Social and Economic Burden of Human Leishmaniasis.

    Okwor, Ifeoma; Uzonna, Jude

    2016-03-01

    Leishmaniasis continues to pose a major public health problem worldwide. With new epidemics occurring in endemic areas and the spread of the disease to previously free areas because of migration, tourism, and military activities, there is a great need for the development of an effective vaccine. Leishmaniasis is a disease of the poor, occurring mostly in remote rural villages with poor housing and little or no access to modern health-care facilities. In endemic areas, diagnosis of any form of leishmaniasis puts a huge financial strain on an already meagre financial resource at both the individual and community levels. Most often families need to sell their assets (land and livestock) or take loans from informal financial outfits with heavy interest rates to pay for the diagnosis and treatment of leishmaniasis. Here, we discuss the disease with special emphasis on its socioeconomic impact on the affected individual and community. In addition, we highlight the reasons why continued research aimed at developing an effective Leishmania vaccine is necessary. PMID:26787156

  7. New serological tools for improved diagnosis of human tegumentary leishmaniasis.

    Costa, Lourena E; Salles, Beatriz C S; Alves, Patrícia T; Dias, Ana C S; Vaz, Emília R; Ramos, Fernanda F; Menezes-Souza, Daniel; Duarte, Mariana C; Roatt, Bruno M; Chávez-Fumagalli, Miguel A; Tavares, Carlos A P; Gonçalves, Denise U; Rocha, Manoel O C; Goulart, Luiz Ricardo; Coelho, Eduardo A F

    2016-07-01

    Human tegumentary leishmaniasis (HTL), characterized by skin ulcers that may spread and cause dreadful and massive tissue destruction of the nose and mouth, is considered a neglected tropical disease, and it is a serious threat to global health due to its continuous expansion, favored by the lifecycle of its causative organism that is maintained in domestic animal reservoirs and anthropophilic sand fly species. Serodiagnosis of HTL is a great challenge due to many biological factors, including hampered specificity and/or sensitivity. This investigation addresses the unmet need for new diagnostic markers of HTL, and describes a simple platform to improve the serodiagnosis. A constrained conformational phage display random peptide library combined with a magnetic microsphere-based subtraction strategy was used to identify ligands with potential diagnostic applications. Six clones were selected against IgG antibodies from HTL patients, characterized by sequencing and confirmed by a phage-ELISA using sera from patients developing visceral leishmaniasis (n=20), Chagas disease (n=10), mucosal (n=30) and cutaneous (n=20) leishmaniasis; as well as from healthy subjects living in endemic (n=20) and non-endemic (n=30) areas of leishmaniasis. A wild-type M13-phage clone and a soluble Leishmania antigenic extract were used as negative and positive controls, respectively. Three clones reached 100% sensitivity and specificity, without any cross-reactivity with sera from patients with leishmaniasis-related diseases. Briefly, we describe for the first time a set of serological markers based on three immunodominant mimotopes that showed 100% accuracy, and that could be used in a phage-ELISA assay for the HTL serodiagnosis. PMID:27090730

  8. 儿童内脏利什曼病相关性噬血细胞性淋巴组织细胞增生症四例临床分析%Visceral leishmaniasis associated hemophagocytic lymphohistiocytosis: report of four childhood cases

    郭霞; 陈娜; 王天有; 周晨燕; 李强; 高举

    2011-01-01

    Objective The clinical features of four cases of visceral leishmaniasis (VL)-associated hemophagocytic lymphohistiocytosis(VL-HLH)were retrospectively analyzed for the purpose of helping the diagnosis of secondary HLH. Method Clinical data of three childhood cases of VL-HLH documented in our hospital and one case diagnosed in the Capital Institute of Pediatrics was reviewed retrospectively,with particular emphasis on peculiar clinical manifestations and on clues to the diagnosis of this relatively rare disease entity.Result Three children were from endemic areas of VL, and the other one had lived in endemic area for one year,which was revealed by detailed history-taking.Clinically,VL-HLH is characterized by persistent fever, hepatosplenomegaly and pancytopenia, which is similar to those of HLH, and is one of the important reasons of delayed diagnosis or misdiagnosis. Based on the HLH-2004 protocol, all the four cases met the diagnostic criteria of HLH. In addition, bone marrow aspirate and immunologic detection of VL-specific antibody via rk39 dipstick test during the early disease course of VL-HLH yielded negative results.Two cases who received HLH-targeted therapy responded reasonably well, with rapid temperature normalization and spleen retraction. Nevertheless,Hb remained lower than normal,which we believed to be related to persistent red cell destruction by the invading parasite Leishmania donovani. Conclusion VL,a parasitic disease caused by Leishmania donovani, which is currently endemic just in 6 provinces in China, shares similar clinical picture of HLH and is an easily ignored underlying cause of secondary HLH.We suggest that VL should be in the list of differential diagnosis for any patients with HLH who lives in or has a definite travel history to endemic areas.Repeated bone marrow studies are highly warranted to make a definite diagnosis of VL, because bone marrow aspirate or rk39 dipstick test during early disease course might yield negative results

  9. Ocular manifestation in canine leishmaniasis

    Ralić Marjan; Jovanović Milan

    2011-01-01

    This paper presents a case of ocular changes in leishmaniasis in a dog brought in for examination because of visible changes in the eyes. An ocular manifestation in leishmaniasis can be bilateral or unilateral. Changes most often occur on the conjunctive and the front segment of the eye, the cornea and iris. From 70 to 80% of dogs diseased with leishmaniasis exhibit frontal uveitis, and dry eye, keratoconjunctivitis sicca, is also a frequent finding. Based ...

  10. Unsupervised Assessment of Subcutaneous and Visceral Fat by MRI

    Jørgensen, Peter Stanley; Larsen, Rasmus; Wraae, Kristian

    This paper presents a. method for unsupervised assessment of visceral and subcutaneous adipose tissue in the abdominal region by MRI. The identification of the subcutaneous and the visceral regions were achieved by dynamic programming constrained by points acquired from an active shape model. The...

  11. A comparative analysis of different molecular targets using PCR for diagnosis of old world leishmaniasis.

    Koltas, Ismail S; Eroglu, Fadime; Uzun, Soner; Alabaz, Derya

    2016-05-01

    The different sensitivity values were obtained in each study conducted for the diagnosis of leishmaniasis with the polymerase chain reaction (PCR). However, a standardized PCR target for the diagnosis of leishmaniasis does not exist. The aim of the current study, the most ideal PCR target was determined for diagnosis of leishmaniasis. A total of 72 smear and 48 bone marrow samples were analyzed with six different molecular targets to determine their potential as a tool for the specific molecular diagnosis of leishmaniasis using PCR. The positivity-negativity value and the sensitivity-specificity of each PCR targets were calculated. The positivity value of PCR targets were sequenced in different levels in the diagnosis of leishmaniasis from highest to lowest in the order of kDNA-PCR > SSU rRNA-PCR > ITS2-PCR > ITS1-PCR > ME-PCR > HSP70-PCR. The sensitivities of PCR targets except ITS1-PCR, ME-PCR and HSP70-PCR were found to be 100% in cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) cases as compared to microscopic examination accepted as a gold standard. The sensitivities of ITS1-PCR, ME-PCR and HSP70-PCR were found 96.6%, 90.0% and 86.6%, respectively, in CL-cases. In addition, the sensitivities of ITS1-PCR, ME-PCR and HSP70-PCR were found 90.0%, 70.0% and 60.0%, respectively, in VL-cases. The kDNA genomic region was the most sensitive for routine diagnosis of leishmaniasis. ITS1-PCR restriction fragment length polymorphism, the alternative method for the identification of Old World Leishmania species, did not require culturing of the parasites. PMID:26896641

  12. Novel nervous system mechanisms in visceral pain.

    De Winter, B Y; Deiteren, A; De Man, J G

    2016-03-01

    Visceral hypersensitivity is an important factor underlying abdominal pain in functional gastrointestinal disorders such as irritable bowel syndrome (IBS) and can result from aberrant signaling from the gut to the brain or vice versa. Over the last two decades, research has identified several selective, intertwining pathways that underlie IBS-related visceral nociception, including specific receptors on afferent and efferent nerve fibers such as transient receptor potential channels (TRP) channels, opioid, and cannabinoid receptors. In this issue of Neurogastroenterology and Motility Gil et al. demonstrate that in an animal model with reduced descending inhibitory control, the sympathetic nervous system outflow is enhanced, contributing to visceral and somatic hypersensitivity. They also provide evidence that interfering with the activation of adrenergic receptors on sensory nerves can be an interesting new strategy to treat visceral pain in IBS. This mini-review places these findings in a broader perspective by providing an overview of promising novel mechanisms to alter the nervous control of visceral pain interfering with afferent or efferent neuronal signaling. PMID:26891060

  13. Immunopathology of post kala-azar dermal leishmaniasis (PKDL): T-cell phenotypes and cytokine profile

    Ismail, A; El Hassan, A M; Kemp, K;

    1999-01-01

    In Sudan, post kala-azar dermal leishmaniasis (PKDL) caused by Leishmania donovani develops in half of the patients treated for visceral leishmaniasis (kala-azar). In most patients lesions heal spontaneously, but in others symptoms are severe and persist for years. This study examined the immunol......In Sudan, post kala-azar dermal leishmaniasis (PKDL) caused by Leishmania donovani develops in half of the patients treated for visceral leishmaniasis (kala-azar). In most patients lesions heal spontaneously, but in others symptoms are severe and persist for years. This study examined...... of macrophages, lymphocytes, and plasma cells. In patients who had high interferon-gamma (IFNgamma) responses to Leishmania antigen in vitro, compact epithelioid granulomas were formed. The inflammatory cells were mainly CD3(+) and interleukin-10 (IL10) was the most prominent cytokine in the lesions. However......, IFNgamma was found in all and IL4 in most lesions, in varying amounts. PBMCs from all patients responded to Leishmania antigen by IFNgamma production or proliferation. The results indicate that PKDL develops as a result of an influx of immunocompetent cells into skin, which harbours parasites...

  14. A review of preventative methods against human leishmaniasis infection.

    Lisa Stockdale

    Full Text Available BACKGROUND: Leishmaniasis is an intracellular parasitic infection transmitted to humans via the sandfly. Approximately 350 million people are at risk of contracting the disease and an estimated 1.6 million new cases occur annually. Of the two main forms, visceral and cutaneous, the visceral form is fatal in 85-90% of untreated cases. AIMS: This literature review aims to identify and evaluate the current evidence base for the use of various preventative methods against human leishmaniasis. METHODS: A literature search was performed of the relevant database repositories for primary research conforming to a priori inclusion and exclusion criteria. RESULTS: A total of 84 controlled studies investigating 12 outcome measures were identified, implementing four broad categories of preventative interventions: animal reservoir control, vector population control, human reservoir control and a category for multiple concurrently implemented interventions. The primary studies investigated a heterogeneous mix of outcome measures using a range of different methods. CONCLUSIONS: This review highlights an absence of research measuring human-specific outcomes (35% of the total across all intervention categories. The apparent inability of study findings to be generalizable across different geographic locations, points towards gaps in knowledge regarding the biology of transmission of Leishmania in different settings. More research is needed which investigates human infection as the primary outcome measure as opposed to intermediate surrogate markers, with a focus on developing a human vaccine.

  15. Coinfection of Cutaneous Leishmaniasis and HIV Infection

    Lartey, Margaret; Adusei, L; Hanson-Nortey, L; Addy, JH

    2006-01-01

    Cutaneous leishmaniasis has recently been discovered in some parts of Ghana. The case of an HIV infected patient presenting with cutaneous leishmaniasis at the Korle-Bu Teaching Hospital is discussed. The diagnosis of leishmaniasis was confirmed by histology. Also highlighted is the fact that this is the first reported case of dual infection of HIV and Leishmaniasis in Ghana.

  16. [The Elba triad: harara, light dermatoses, leishmaniasis. The ecological background].

    Krampitz, H E

    1981-05-01

    A report is given on a travel to Elba, the largest island of the Tuscany archepelago (Italy) and a holiday place preferred by German speaking tourists. In the last years some cases of visceral leishmaniasis and oriental sores, respectively, were introduced to Germany from this island. The geoecological background of this development was investigated. Reproduction and spread of the most abundant sandfly species Phlebotomus (Laroussius) perniciosus favour ruinous buildings, actually used as animal shelters sometimes in the immediate vicinity of new tourist bungalows. A typical allergic response upon sandfly bites occurs in almost all of the newcomers. This skin irritation is wellknown as urticaria multiformis endemica of Harara. Local people and tourists connect this itching disorder with certain types of sun trauma and do not take notice of their real etiology. Cortisone treatment in severe cases may facilitate the start of simultaneously transmitted leishmaniasis. The possible epidemiological role, which the dog travelling to southern countries in connection with leishmaniasis plays, is considered. PMID:7016813

  17. Ear, nose and throat manifestations of mucocutaneous Leishmaniasis: a literature review.

    Marra, Francesca; Chiappetta, Maria Celeste; Vincenti, Vincenzo

    2014-01-01

    ABSTRACT Leishmaniasis comprises a group of diseases caused by a protozoan parasite belonging to the genus Leishmania and transmitted by the bite of infected female sand flies. Leishmaniasis is endemic in 88 countries and causes significant morbidity and mortality worldwide. Phenomena such as globalization and human migration, as well as the increased volume of international travel have extended its prevalence in developed countries. In addition, the incidence of leishmaniasis as an opportunistic disease has increased in recent years because of the growing number of patients with immune depression secondary to chronic illness, neoplasm, transplant and HIV infection, thereby constituting a public health problem. In humans, there are three possible clinical syndromes of leishmaniasis: cutaneous, mucocutaneous and visceral. Mucocutaneous disease is due to extension of local skin disease into the mucosal tissue via direct extension, bloodstream or lymphatics. Lesions interest mainly the oral and nasal mucosa and occasionally the laryngeal and pharyngeal mucosa. If not recognized and adequately treated, MCL may disfigure the patient because of the chronic local destruction of tissue of the nose, pharynx and palate. Because of the invariable involvement of the areas pertaining otorhinolaryngologists, it is important for ENT specialists and family physicians to have awareness of this condition and its clinical manifestations, particularly in presence of a history positive for travel to endemic areas. If mucocutaneous leishmaniasis is suspected, otorhinolaryngologic examination is very helpful in establishing a correct diagnosis, preventing inappropriate treatment. PMID:24897964

  18. Angiotensin I-converting enzyme (ACE) inhibitory activities of sardinelle (Sardinella aurita) by-products protein hydrolysates obtained by treatment with microbial and visceral fish serine proteases.

    Bougatef, Ali; Nedjar-Arroume, Naima; Ravallec-Plé, Rozenn; Leroy, Yves; Guillochon, Didier; Barkia, Ahmed; Nasri, Moncef

    2008-11-15

    The angiotensin I-converting enzyme (ACE) inhibitory activities of protein hydrolysates prepared from heads and viscera of sardinelle (Sardinella aurita) by treatment with various proteases were investigated. Protein hydrolysates were obtained by treatment with Alcalase(®), chymotrypsin, crude enzyme preparations from Bacillus licheniformis NH1 and Aspergillus clavatus ES1, and crude enzyme extract from sardine (Sardina pilchardus) viscera. All hydrolysates exhibited inhibitory activity towards ACE. The alkaline protease extract from the viscera of sardine produced hydrolysate with the highest ACE inhibitory activity (63.2±1.5% at 2mg/ml). Further, the degrees of hydrolysis and the inhibitory activities of ACE increased with increasing proteolysis time. The protein hydrolysate generated with alkaline proteases from the viscera of sardine was then fractionated by size exclusion chromatography on a Sephadex G-25 into eight major fractions (P1-P8). Biological functions of all fractions were assayed, and P4 was found to display a high ACE inhibitory activity. The IC50 values for ACE inhibitory activities of sardinelle by-products protein hydrolysates and fraction P4 were 1.2±0.09 and 0.81±0.013mg/ml, respectively. Further, P4 showed resistance to in vitro digestion by gastrointestinal proteases. The amino acid analysis by GC/MS showed that P4 was rich in phenylalanine, arginine, glycine, leucine, methionine, histidine and tyrosine. The added-value of sardinelle by-products may be improved by enzymatic treatment with visceral serine proteases from sardine. PMID:26047434

  19. The Pharmacology of Visceral Pain.

    Johnson, Anthony C; Greenwood-Van Meerveld, Beverley

    2016-01-01

    Visceral pain describes pain emanating from the internal thoracic, pelvic, or abdominal organs. Unlike somatic pain, visceral pain is generally vague, poorly localized, and characterized by hypersensitivity to a stimulus such as organ distension. While current therapeutics provides some relief from somatic pain, drugs used for treatment of chronic visceral pain are typically less efficacious and limited by multiple adverse side effects. Thus, the treatment of visceral pain represents a major unmet medical need. Further, more basic research into the physiology and pathophysiology of visceral pain is needed to provide novel targets for future drug development. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. However, persistent stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders. We will focus on stress-induced exacerbation of chronic visceral pain and provide supporting evidence that centrally acting drugs targeting the pain and stress-responsive brain regions may represent a valid target for the development of novel and effective therapeutics. PMID:26920016

  20. Periungual leishmaniasis Leishmaniose periungueal

    Ciro Martins Gomes

    2012-02-01

    Full Text Available The vast majority of cases of cutaneous leishmaniasis are represented by limb injuries. A female patient, white, presented an ulcer with infiltrated borders located on the fourth finger of the left hand following occupational exposure in an area of native forest. Diagnosis of cutaneous leishmaniasis caused by Leishmania of the subgenus Viannia was confirmed. The patient failed to respond to treatment with antimony, but achieved clinical cure after this was associated with pentoxifylline. The case highlights the rarity of the periungual location of the leishmanial lesion and the difficulties encountered in therapy.A grande maioria dos casos de leishmaniose tegumentar é representada por lesões nos membros. Paciente feminina, branca, diabética, apresentou úlcera com bordas infiltradas, localizada no quarto quirodáctilo esquerdo, após exposição ocupacional em área de mata nativa. Foi confirmado o diagnóstico de leishmaniose tegumentar por Leishmania do subgênero Viannia. Não respondeu ao tratamento com antimonial, mas obteve cura clínica após associação com a pentoxifilina. O caso destaca-se pela raridade da localização periungueal da lesão leishmaniótica e pela dificuldade terapêutica.