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Sample records for active visceral leishmaniasis

  1. [Visceral leishmaniasis: new drugs].

    Science.gov (United States)

    Minodier, P; Robert, S; Retornaz, K; Garnier, J M

    2003-12-01

    The standard treatment of visceral leishmaniasis is pentavalent antimony (meglumine antimoniate or sodium stibogluconate), but toxicity is frequent with this drug. Moreover, antimony unresponsiveness is increasing, both in immunocompetent and in immunosuppressed patients. Amphotericin B is a polyene macrolide antibiotic that binds to sterols in cell membranes. It is the most active antileishmanial agent in use. Its infusion-related and renal toxicity may be reduced by lipid-based delivery. Liposomal amphotericin B (Ambisome) seems to be less toxic than other amphotericin B lipid formulations (Amphocil, Amphotec). Optimal drug regimens of Ambisome vary from one geographical area to another. In the Mediterranean Basin, a total dose of 18 to 24 mg/kg is safe and effective. Shortening the duration of treatment without decreasing the total dose (i.e., 10 mg/kg/day for 2 days) seems promising to reduce the global cost of the therapy.

  2. Immunity and immunosuppression in experimental visceral leishmaniasis

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    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

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    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

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    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

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    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. Visceral leishmaniasis in Aba-Roba, south-western Ethiopia: prevalence and incidence of active and subclinical infections

    NARCIS (Netherlands)

    A. Hailu; M. Gramiccia; P.A. Kager

    2009-01-01

    Between August 1997 and February 2005, a prospective study of human visceral leishmaniasis (VL) was undertaken in two villages in the Konso district of south-western Ethiopia, to provide epidemiological indices of subclinical infection and active VL. Six cross-sectional surveys at 6-month intervals

  7. Circulating Biomarkers of Immune Activation, Oxidative Stress and Inflammation Characterize Severe Canine Visceral Leishmaniasis

    Science.gov (United States)

    Solcà, Manuela S.; Andrade, Bruno B.; Abbehusen, Melissa Moura Costa; Teixeira, Clarissa R.; Khouri, Ricardo; Valenzuela, Jesus G.; Kamhawi, Shaden; Bozza, Patrícia Torres; Fraga, Deborah Bittencourt Mothé; Borges, Valeria Matos; Veras, Patrícia Sampaio Tavares; Brodskyn, Claudia Ida

    2016-01-01

    Clinical manifestations in canine visceral leishmaniasis (CVL) have not been clearly associated with immunological status or disease progression. We simultaneously assessed biomarkers of inflammation, immune activation, oxidative stress, and anti-sand fly saliva IgG concentrations in dog sera with different clinical manifestations to characterize a biosignature associated with CVL severity. In a cross-sectional exploratory study, a random population of 70 dogs from an endemic area in Brazil was classified according to CVL clinical severity and parasitological evaluation. A panel of biomarkers and anti–sand fly saliva IgG were measured in canine sera. Assessment of protein expression of profile biomarkers identified a distinct biosignature that could cluster separately animal groups with different clinical scores. Increasing severity scores were associated with a gradual decrease of LTB4 and PGE2, and a gradual increase in CXCL1 and CCL2. Discriminant analyses revealed that combined assessment of LTB4, PGE2 and CXCL1 was able to distinguish dogs with different clinical scores. Dogs with the highest clinical score values also exhibited high parasite loads and higher concentrations of anti-saliva antibodies. Our findings suggest CVL clinical severity is tightly associated with a distinct inflammatory profile hallmarked by a differential expression of circulating eicosanoids and chemokines. PMID:27595802

  8. Visceral Leishmaniasis In A Native Kashmiri Boy

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    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.

  9. Accelerated active case detection of visceral leishmaniasis patients in endemic villages of Bangladesh.

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    Jahanara Khatun

    Full Text Available BACKGROUND: The visceral leishmaniasis (VL elimination program in Bangladesh is in its attack phase. The primary goal of this phase is to decrease the burden of VL as much as possible. Active case detection (ACD by the fever camp method and an approach using past VL cases in the last 6-12 months have been found useful for detection of VL patients in the community. We aimed to explore the yield of Accelerated Active Case Detection (AACD of non-self reporting VL as well as the factors that are associated with non-self reporting to hospitals in endemic communities of Bangladesh. METHODS: Our study was conducted in the Trishal sub-district of Mymensingh, a highly VL endemic region of Bangladesh. We used a two-stage sampling strategy from 12 VL endemic unions of Trishal. Two villages from each union were selected at random. We looked for VL patients who had self-reported to the hospital and were under treatment from these villages. Then we conducted AACD for VL cases in those villages using house-to-house visit. Suspected VL cases were referred to the Trishal hospital where diagnosis and treatment of VL was done following National Guidelines for VL case management. We collected socio-demographic information from patients or a patient guardian using a structured questionnaire. RESULTS: The total number of VL cases was 51. Nineteen of 51 (37.3% were identified by AACD. Poverty, female gender and poor knowledge about VL were independent factors associated with non self-reporting to the hospital. CONCLUSION: Our primary finding is that AACD is a useful method for early detection of VL cases that would otherwise go unreported to the hospital in later stage due to poverty, poor knowledge about VL and gender inequity. We recommend that the National VL Program should consider AACD to strengthen its early VL case detection strategy.

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

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    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.

  11. Killed but metabolically active Leishmania infantum as a novel whole-cell vaccine for visceral leishmaniasis.

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    Bruhn, Kevin W; Birnbaum, Ron; Haskell, Jacquelyn; Vanchinathan, Veena; Greger, Stephanie; Narayan, Rupa; Chang, Pei-Lin; Tran, Thu Anh; Hickerson, Suzanne M; Beverley, Stephen M; Wilson, Mary E; Craft, Noah

    2012-04-01

    There are currently no effective vaccines for visceral leishmaniasis, the second most deadly parasitic infection in the world. Here, we describe a novel whole-cell vaccine approach using Leishmania infantum chagasi promastigotes treated with the psoralen compound amotosalen (S-59) and low doses of UV A radiation. This treatment generates permanent, covalent DNA cross-links within parasites and results in Leishmania organisms termed killed but metabolically active (KBMA). In this report, we characterize the in vitro growth characteristics of both KBMA L. major and KBMA L. infantum chagasi. Concentrations of S-59 that generate optimally attenuated parasites were identified. Like live L. infantum chagasi, KBMA L. infantum chagasi parasites were able to initially enter liver cells in vivo after intravenous infection. However, whereas live L. infantum chagasi infection leads to hepatosplenomegaly in mice after 6 months, KBMA L. infantum chagasi parasites were undetectable in the organs of mice at this time point. In vitro, KBMA L. infantum chagasi retained the ability to enter macrophages and induce nitric oxide production. These characteristics of KBMA L. infantum chagasi correlated with the ability to prophylactically protect mice via subcutaneous vaccination at levels similar to vaccination with live, virulent organisms. Splenocytes from mice vaccinated with either live L. infantum chagasi or KBMA L. infantum chagasi displayed similar cytokine patterns in vitro. These results suggest that KBMA technology is a potentially safe and effective novel vaccine strategy against the intracellular protozoan L. infantum chagasi. This approach may represent a new method for whole-cell vaccination against other complex intracellular pathogens.

  12. Oral mucosal involvement in visceral leishmaniasis

    Institute of Scientific and Technical Information of China (English)

    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.

  13. Vaccines for visceral leishmaniasis: A review.

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    Jain, Keerti; Jain, N K

    2015-07-01

    Visceral leishmaniasis, which is also known as Kala-Azar, is one of the most severely neglected tropical diseases recognized by the World Health Organization (WHO). The threat of this debilitating disease continues due to unavailability of promising drug therapy or human vaccine. An extensive research is undergoing to develop a promising vaccine to prevent this devastating disease. In this review we compiled the findings of recent research with a view to facilitate knowledge on experimental vaccinology for visceral leishmaniasis. Various killed or attenuated parasite based first generation vaccines, second generation vaccines based on antigenic protein or recombinant protein, and third generation vaccines derived from antigen-encoding DNA plasmids including heterologous prime-boost Leishmania vaccine have been examined for control and prevention of visceral leishmaniasis. Vaccines based on recombinant protein and antigen-encoding DNA plasmids have given promising results and few vaccines including Leishmune®, Leishtec, and CaniLeish® have been licensed for canine visceral leishmaniasis. A systematic investigation of these vaccine candidates can lead to development of promising vaccine for human visceral leishmaniasis, most probably in the near future.

  14. Development of Vaccines against Visceral Leishmaniasis

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    Krystal J. Evans

    2012-01-01

    Full Text Available Leishmaniasis is a neglected disease resulting in a global morbidity of 2,090 thousand Disability-Adjusted Life Years and a mortality rate of approximately 60,000 per year. Among the three clinical forms of leishmaniasis (cutaneous, mucosal, and visceral, visceral leishmaniasis (VL accounts for the majority of mortality, as if left untreated VL is almost always fatal. Caused by infection with Leishmania donovani or L. infantum, VL represents a serious public health problem in endemic regions and is rapidly emerging as an opportunistic infection in HIV patients. To date, no vaccine exists for VL or any other form of leishmaniasis. In endemic areas, the majority of those infected do not develop clinical symptoms and past infection leads to robust immunity against reinfection. Thus the development of vaccine for Leishmania is a realistic public health goal, and this paper summarizes advances in vaccination strategies against VL.

  15. Intraretinal hemorrhage associated with visceral leishmaniasis

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    Ricardo Evangelista Marrocos de Aragão

    2015-12-01

    Full Text Available ABSTRACT Visceral Leishmaniasis, also know as Kala-azar, is a parasitic tropical disease caused by protozoa of the genus Leishmania donovani. It is an endemic disease in many countries. It affects approximately 1,5 million people every year, and when associated with mal-nutrition and co-infection it may be fatal. Fever, hepatosplenomegaly, and pancytopenia is its typical clinical picture. Ocular manifestations of Kalaazar are relatively rare and can affect either anterior or posterior segment of the eye. We report a patient with kala-azar presenting intraretinal hemorrhages that regress completely after the successful treatment for visceral leishmaniasis.

  16. Epistaxis in Visceral Leishmaniasis with Hematological Correlation

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    Sigdel, B.; Bhandary, S.; Rijal, S

    2012-01-01

    Objective. To study the prevalence of epistaxis in visceral leismaniasis and its correlation with hematological profile. Methods. Out of 80 diagnosed cases of visceral leishmaniasis, 19 patients with epistaxis were included in the study. Diagnosis was made by Rk-39 from peripheral smear and LD bodies from bone marrow. Before starting anti-kala-azar treatment, nasal examination findings and hematological profile were noted. Study Design. Prospective cross-sectional hospital-based study. Result...

  17. Hemophagocytic lymphohistiocytosis in children with visceral leishmaniasis.

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    Blázquez-Gamero, Daniel; Domínguez-Pinilla, Nerea; Chicharro, Carmen; Negreira, Sagrario; Galán, Pilar; Pérez-Gorricho, Beatriz; Calvo, Cristina; Prieto, Luis; De la Parte, María; Otheo, Enrique; Vivanco, Jose Luis; Ruiz-Contreras, Jesús

    2015-06-01

    Acquired hemophagocytic lymphohistiocitosis (HLH) syndrome can be a complication of visceral leishmaniasis (VL). A multicenter prospective study was conducted to determine the frequency of HLH syndrome in children with VL. Twenty-four children with VL were identified, and 10 (41%) developed HLH syndrome. VL should be ruled out in all children with HLH criteria living in or coming from endemic areas.

  18. Sexual and vertical transmission of visceral leishmaniasis.

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    Turchetti, Andreia P; Souza, Tayse D; Paixão, Tatiane A; Santos, Renato L

    2014-04-15

    Visceral leishmaniasis (VL) is an important zoonosis caused by Leishmania infantum, which has in the domestic dog its principal vertebrate host. VL is usually transmitted by phlebotomine sand flies, however atypical routes of transmission have been described. In this review we discuss the the role of sexual and vertical transmissions, and their role in the maintenance of VL in canine populations.

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

    NARCIS (Netherlands)

    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

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

    DEFF Research Database (Denmark)

    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...

  1. Epistaxis in visceral leishmaniasis with hematological correlation.

    Science.gov (United States)

    Sigdel, B; Bhandary, S; Rijal, S

    2012-01-01

    Objective. To study the prevalence of epistaxis in visceral leismaniasis and its correlation with hematological profile. Methods. Out of 80 diagnosed cases of visceral leishmaniasis, 19 patients with epistaxis were included in the study. Diagnosis was made by Rk-39 from peripheral smear and LD bodies from bone marrow. Before starting anti-kala-azar treatment, nasal examination findings and hematological profile were noted. Study Design. Prospective cross-sectional hospital-based study. Results. Epistaxis was found in the age group of 7-66 years. Epistaxis was observed in 19 (23.8%) cases. One patient died because of epistaxis and neck hematoma. Conclusion. Epistaxis is a common ENT finding in endemic area of visceral leishmaniasis like our case.

  2. Epistaxis in Visceral Leishmaniasis with Hematological Correlation

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    B. Sigdel

    2012-01-01

    Full Text Available Objective. To study the prevalence of epistaxis in visceral leismaniasis and its correlation with hematological profile. Methods. Out of 80 diagnosed cases of visceral leishmaniasis, 19 patients with epistaxis were included in the study. Diagnosis was made by Rk-39 from peripheral smear and LD bodies from bone marrow. Before starting anti-kala-azar treatment, nasal examination findings and hematological profile were noted. Study Design. Prospective cross-sectional hospital-based study. Results. Epistaxis was found in the age group of 7–66 years. Epistaxis was observed in 19 (23.8% cases. One patient died because of epistaxis and neck hematoma. Conclusion. Epistaxis is a common ENT finding in endemic area of visceral leishmaniasis like our case.

  3. Leishmaniasis visceral: senderos que confluyen, se bifurcan

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    Oscar Daniel Salomón

    2012-01-01

    Full Text Available La leishmaniasis visceral urbana es una zoonosis emergente en Argentina. En América es producida por Leishmania infantum, con el perro como reservorio principal e insectos flebotomíneos como vectores. En este artículo se presenta el conocimiento acumulado a partir de su emergencia y dispersión en el país, por los referentes del Programa Nacional de Leishmaniasis, en el diagnóstico clínico y de laboratorio, tratamiento, biología de vectores, manejo de reservorio, y el conflicto generado con las acciones recomendadas en relación con los perros infectados. La detección temprana y el tratamiento precoz, con estrategias descentralizadas y horizontales, contribuirán a disminuir la morbimortalidad asociada a la leishmaniasis visceral. El control de su transmisión y dispersión requiere de un manejo ambiental integral y la tenencia responsable de perros. Se discuten los intereses y discursos en conflicto generados por la leishmaniasis visceral en el marco de la relación humano-perro, proponiendo la búsqueda de un discurso consensuado de riesgo.

  4. Leishmaniasis visceral: senderos que confluyen, se bifurcan

    OpenAIRE

    Oscar Daniel Salomón; Andrea Verónica Mastrángelo; María Soledad Santini; Silvina Ruvinsky; Tomás Orduna; Angel Sinagra; Concepción Luna; Adelina Riarte; Natalia Casas; Paola Amiotti

    2012-01-01

    La leishmaniasis visceral urbana es una zoonosis emergente en Argentina. En América es producida por Leishmania infantum, con el perro como reservorio principal e insectos flebotomíneos como vectores. En este artículo se presenta el conocimiento acumulado a partir de su emergencia y dispersión en el país, por los referentes del Programa Nacional de Leishmaniasis, en el diagnóstico clínico y de laboratorio, tratamiento, biología de vectores, manejo de reservorio, y el conflicto generado con la...

  5. Canine visceral leishmaniasis: comparison of in vitro leishmanicidal activity of marbofloxacin, meglumine antimoniate and sodium stibogluconate.

    Science.gov (United States)

    Vouldoukis, Ioannis; Rougier, Sandrine; Dugas, Bernard; Pino, Paco; Mazier, Dominique; Woehrlé, Frédérique

    2006-01-30

    The control of canine leishmaniasis largely depends on the success of treatment. Drugs currently available to treat this disease are toxic and partially effective. The curative effect of marbofloxacin, a third-generation fluoroquinolone developed for veterinarian individual treatment, was evaluated in vitro in the presence of Leishmania infantum promastigotes and dog-monocyte-derived macrophages; meglumine antimoniate and sodium stibogluconate were used as comparative treatments. We observed that the killing of Leishmania promastigotes and intracellular amastigotes by marbofloxacin was dose-dependent. We demonstrated that successful treatment of canine infected macrophages for 48 h was possible with 500 microg/ml of marbofloxacin. Leishmanicidal activity acted through a TNF-alpha and nitric oxide pathway and correlated with the generation of nitric oxide (NO(2)) production by monocytes derived macrophages from infected (23+/-5 microM) or healthy (21+/-6 microM) dogs, in comparison with NO(2) concentration in infected/non-treated macrophages (Marbofloxacin was shown to be non-toxic at 500 microg/ml in vitro and no cell apoptosis was observed. The molecule was able to induce a parasitic process after significant elimination of amastigotes in leishmania-infected dog macrophages. We propose that marbofloxacin, compared to standard chemotherapeutic agents (meglumine antimoniate and sodium stibogluconate), could be an effective and pragmatic oral route alternative to treat canine leishmaniasis.

  6. Intraretinal hemorrhage associated with visceral leishmaniasis

    OpenAIRE

    Ricardo Evangelista Marrocos de Aragão; Barreira,Ieda Maria A.; Leidiane Alexandre Pereira; Arrais,Barbara Lorena A.; Francisco Holanda Oliveira Neto; Everton Fernandes Vieira de Almeida; André Jucá Machado

    2015-01-01

    ABSTRACT Visceral Leishmaniasis, also know as Kala-azar, is a parasitic tropical disease caused by protozoa of the genus Leishmania donovani. It is an endemic disease in many countries. It affects approximately 1,5 million people every year, and when associated with mal-nutrition and co-infection it may be fatal. Fever, hepatosplenomegaly, and pancytopenia is its typical clinical picture. Ocular manifestations of Kalaazar are relatively rare and can affect either anterior or posterior segment...

  7. Nocturnal activity patterns of Lutzomyia longipalpis (Diptera: Psychodidae) at an endemic focus of visceral leishmaniasis in Colombia.

    Science.gov (United States)

    Morrison, A C; Ferro, C; Pardo, R; Torres, M; Wilson, M L; Tesh, R B

    1995-09-01

    Nocturnal activity of the sand fly Lutzomyia longipalpis (Lutz & Neiva) was studied from August 1991 to July 1992 in a small rural community in Colombia where American visceral leishmaniasis is endemic. During 2 or 3 nights each month, sand flies were collected with hand-held aspirators each hour between 1730 and 0630 hours, from a pigpen and a cattle corral located 30 m apart. Host-seeking activity of L. longipalpis adults was characterized by 2 general patterns: (1) adult sand fly activity increased shortly after sunset and continued until just after sunrise, and (2) peak sand fly activity was greatest early in the evening (1830-2330 hours) and then declined steadily toward morning. Female L. longipalpis activity generally increased after 2030 hours, whereas that of males remained constant or declined as the evening progressed. There were seasonal differences in sand fly abundance between the 2 sites: peak abundance in the cattle corral occurred during hot, dry periods, whereas maximum abundance in the pigpen occurred when relative humidity was higher. Influence of relative humidity on activity varied with season. Sand fly activity tended to decrease at temperatures below 24 degrees C and increase in the presence of moonlight.

  8. Active case detection in national visceral leishmaniasis elimination programs in Bangladesh, India, and Nepal: feasibility, performance and costs

    Directory of Open Access Journals (Sweden)

    Huda M

    2012-11-01

    Full Text Available Abstract Background Active case detection (ACD significantly contributes to early detection and treatment of visceral leishmaniasis (VL and post kala-azar dermal leishmaniasis (PKDL cases and is cost effective. This paper evaluates the performance and feasibility of adapting ACD strategies into national programs for VL elimination in Bangladesh, India and Nepal. Methods The camp search and index case search strategies were piloted in 2010-11 by national programs in high and moderate endemic districts / sub-districts respectively. Researchers independently assessed the performance and feasibility of these strategies through direct observation of activities and review of records. Program costs were estimated using an ingredients costing method. Results Altogether 48 camps (Bangladesh-27, India-19, Nepal-2 and 81 index case searches (India-36, Nepal-45 were conducted by the health services across 50 health center areas (Bangladesh-4 Upazillas, India-9 PHCs, Nepal-37 VDCs. The mean number of new case detected per camp was 1.3 and it varied from 0.32 in India to 2.0 in Bangladesh. The cost (excluding training costs of detecting one new VL case per camp varied from USD 22 in Bangladesh, USD 199 in Nepal to USD 320 in India. The camp search strategy detected a substantive number of new PKDL cases. The major challenges faced by the programs were inadequate preparation, time and resources spent on promoting camp awareness through IEC activities in the community. Incorrectly diagnosed splenic enlargement at camps probably due to poor clinical examination skills resulted in a high proportion of patients being subjected to rK39 testing. Conclusion National programs can adapt ACD strategies for detection of new VL/PKDL cases. However adequate time and resources are required for training, planning and strengthening referral services to overcome challenges faced by the programs in conducting ACD.

  9. Epidemiology of visceral leishmaniasis in Georgia.

    Directory of Open Access Journals (Sweden)

    Giorgi Babuadze

    2014-03-01

    Full Text Available This study investigated the transmission and prevalence of Leishmania parasite infection of humans in two foci of Visceral Leishmaniasis (VL in Georgia, the well known focus in Tbilisi in the East, and in Kutaisi, a new focus in the West of the country. The seroprevalence of canine leishmaniasis was investigated in order to understand the zoonotic transmission. Blood samples of 1575 dogs (stray and pet and 77 wild canids were tested for VL by Kalazar Detect rK39 rapid diagnostic tests. Three districts were investigated in Tbilisi and one in Kutaisi. The highest proportions of seropositive pet dogs were present in District #2 (28.1%, 82/292 and District #1 (26.9%, 24/89 in Tbilisi, compared to 17.3% (26/150 of pet dogs in Kutaisi. The percentage of seropositive stray dogs was also twice as high in Tbilisi (16.1%, n = 670 than in Kutaisi (8%, n = 50; only 2/58 wild animals screened were seropositive (2. 6%. A total of 873 Phlebotomine sand flies were collected, with 5 different species identified in Tbilisi and 3 species in Kutaisi; 2.3% of the females were positive for Leishmania parasites. The Leishmanin Skin Test (LST was performed on 981 human subjects in VL foci in urban areas in Tbilisi and Kutaisi. A particularly high prevalence of LST positives was observed in Tbilisi District #1 (22.2%, 37.5% and 19.5% for ages 5-9, 15-24 and 25-59, respectively; lower prevalence was observed in Kutaisi (0%, 3.2% and 5.2%, respectively; P<0.05. This study shows that Tbilisi is an active focus for leishmaniasis and that the infection prevalence is very high in dogs and in humans. Although exposure is as yet not as high in Kutaisi, this is a new VL focus. The overall situation in the country is alarming and new control measures are urgently needed.

  10. [Visceral leishmaniasis in an HIV positive patient].

    Science.gov (United States)

    Rossiere-Echazarreta, Natalia Lorena; Rodríguez-Campos, Esther Alicia; Morales-Esponda, Mario; Domínguez-Moreno, Rogelio; Cruz-Ortiz, Margarita; Rodríguez-Guzmán, Leoncio Miguel

    2013-01-01

    Introducción: la leishmaniasis visceral o kala azar es la presentación clínica más grave. En México, es una enfermedad rara por lo que su diagnóstico es tardío y generalmente culmina en la muerte del paciente. Se describe a un paciente VIH positivo que desarrolló leishmaniasis visceral. El objetivo es explicar sus características fisiopatológicas y de su tratamiento. Caso clínico: hombre de 45 años de edad, quien ingresó al hospital por cuadro crónico de diarrea sanguinolenta, distensión abdominal, dolor tipo cólico, pérdida de peso y fiebre. A la exploración física se identificó paciente febril con dolor en fosa iliaca derecha y hepatoesplenomegalia. La prueba ELISA para VIH resultó positiva y el ultrasonido hizo evidente una tumoración en ciego, por lo que se realizó biopsia. El informe histopatológico indicó que se trataba de leishmaniasis. Conclusiones: en los pacientes con leishmaniasis e infección por VIH existe pobre respuesta al tratamiento y la mortalidad es alta, causada por la menor respuesta inmune del huésped. En la literatura especializada se sugiere el tratamiento establecido para la infección por VIH combinado con miltefosine y anfotericina B liposomal para la leishmaniasis.

  11. Genetically modified organisms and visceral leishmaniasis.

    Science.gov (United States)

    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 largest parasite killers of the world, second only to malaria. There are three types of leishmaniasis 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.

  12. Immune regulation during chronic visceral leishmaniasis.

    Science.gov (United States)

    Faleiro, Rebecca J; Kumar, Rajiv; Hafner, Louise M; Engwerda, Christian R

    2014-07-01

    Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs, and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed.

  13. Genetically Modified Organisms and Visceral Leishmaniasis

    Directory of Open Access Journals (Sweden)

    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.

  14. Laboratory diagnosis of human visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    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.

  15. Causes of pediatric visceral leishmaniasis in southeastern iran.

    Directory of Open Access Journals (Sweden)

    Ali Hosseininasab

    2014-12-01

    Full Text Available 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 of visceral leishmaniasis and one L.tropica as a minor species.

  16. Visceral leishmaniasis diagnosed in a patient with MALT lymphoma

    DEFF Research Database (Denmark)

    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....

  17. NEWER DRUGS FOR VISCERAL LEISHMANIASIS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Krishna Pandey

    2014-01-01

    Full Text Available Visceral Leishmaniasis (VL is one of the most neglected tropical diseases worldwide. The diagnosis and treatment of this disease is quite complex. Sodium Antimony Gluconate (SAG which used to be a very effective treatment has now developed resistance and is potentially a cardio-toxic drug. Pentamidine has now been discarded because of adverse effect of diabetes mellitus. Amphotericin-B is an effective drug but can cause nephrotoxicity. Miltefosine is a new oral effective drug which has recently been introduced in the kala-azar elimination program in the Indian subcontinent. Paromomycin is an injectable aminoglycoside which is quite cheap but can cause ototoxicity and nephrotoxicity. Sitamaquine, an oral antimalarial drug is still in phase-II trial stage. Combination Therapy is been tried with good results. Single dose Ambisome (liposomal Amphotericin-B though costly is a very good alternative.

  18. Hyponatremia in visceral leishmaniasis Hiponatremia no calazar

    OpenAIRE

    Frederico A. Lima Verde; Francisco A.A. Lima Verde; Francisco José V. Veronese; Augusto S. Neto; Galdino Fuc; Emir M. Lima Verde

    2010-01-01

    There are few reports linking hyponatremia and visceral leishmaniasis (kala-azar). This is a study of 55 consecutive kala-azar patients and 20 normal individuals as a control group. Hyponatremia and serum hypo-osmolality were detected in 100% of kala-azar patients. High first morning urine osmolality (750.0 ± 52.0 vs. 894.5 ± 30.0mOsm/kg H2O, p < 0.05), and high 24-hour urine osmolality (426.0 ± 167.0 vs. 514.6 ± 132.0 mOsm/kg H2O, p < 0.05) demonstrated persistent antidiuretic hormone secret...

  19. [Importance of drug carriers in the treatment of visceral leishmaniasis].

    Science.gov (United States)

    Fusai, T; Durand, R; Boulard, Y; Paul, M; Bories, C; Rivollet, D; Houin, R; Deniau, M

    1995-01-01

    Visceral leishmaniasis is caused by hemoflagellate protozoa which are obligatory parasites of the mononuclear phagocyte system. Leishmaniasis causes high morbidity and mortality worldwide. The treatment of choice remains pentavalent antimonials, but high toxicity and failures have been reported. An alternative to conventional treatment is delivery anti-leishmania agents using colloidal carrier systems. Carriers improve drug activity against intracellular disease involving the mononuclear phagocyte system. The principle of drug delivery by carrier systems has been applied successfully for anticancer drugs. Recently complete remission of polyresistant visceral leishmaniasis was obtained by injection of liposomal amphotericin B. At present, no colloidal drug carrier for antimony derivatives is available, but pentamidine can be linked experimentally to methacrylate polymer nano-particles. Drug-loaded nanoparticles have been shown to be effective against amastigote leishmania both in vitro and in vivo. Another colloidal system of major interest for drug delivery, the liposome has already been loaded with amphotericin B and used for human therapy. The concept of particulate drug carriers opens the way for new chemotherapeutic approaches in the field of parasitology.

  20. RENAL HISTOPATHOLOGICAL FINDINGS IN DOGS WITH VISCERAL LEISHMANIASIS

    OpenAIRE

    Rosangela Silva Rigo; Cristiano Marcelo Espínola Carvalho; Michael Robin Honer; Gisele Braziliano de Andrade; Iandara Shetter Silva; Leonardo Rigo; Helen Rezende Figueiredo; Wanessa Teixeira Gomes Barreto

    2013-01-01

    Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL). Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05) between the presence of glomerulonephritis in symptomatic...

  1. Animal reservoirs for visceral leishmaniasis in densely populated urban areas.

    Science.gov (United States)

    Diniz, Soraia A; Silva, Fabiana L; Carvalho Neta, Alcina C; Bueno, Regina; Guerra, Rita M S N C; Abreu-Silva, Ana L; Santos, Renato L

    2008-02-01

    Leishmaniasis is a zoonotic disease of major public health and veterinary importance, affecting 88 countries with up to 2 million cases per year. This review emphasizes the animal reservoirs and spreading of visceral leishmaniasis (VL) in urban areas, particularly in two Brazilian metropolitan areas, namely São Luis and Belo Horizonte, where the disease has become endemic in the past few years. Urbanization of visceral leishmaniasis in Brazil during the last decades has created favorable epidemiological conditions for maintenance of the disease, with dense human populations sharing a tropical environment with abundant populations of the mammalian reservoir and the invertebrate vector, facilitating transmission of the disease.

  2. Human visceral leishmaniasis: a picture from Italy.

    Science.gov (United States)

    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.

  3. The organization of health services and visceral leishmaniasis: an integrated intervention to improve diagnosis and treatment.

    Science.gov (United States)

    Luz, Zélia M P; Carneiro, Mariângela; Schall, Virgínia; Rabello, Ana

    2009-05-01

    The objective of this study, carried out in municipalities located in a metropolitan region of Brazil, was to promote the early diagnosis and prompt treatment of visceral leishmaniasis. In the intervention model a health professional underwent training that covered all procedures involved in assisting patients with suspected visceral leishmaniasis. The professionals then returned to their municipalities where they implemented a workplan with the following aims: (a) at least one physician able to diagnose and treat patients; (b) training of professionals for the laboratorial diagnosis of visceral leishmaniasis; (c) delivery of information on visceral leishmaniasis to the health workers. The implementation process was evaluated by follow-up meetings. Attendance of health professionals at the meetings, implementation of the workplan, and the visceral leishmaniasis case fatality rate before (1998-1999) and after (2001-2002) implementation of the model were used in the analysis. Among the 36 municipalities in the region, 22 were enrolled. Eight (36.3%) guaranteed at least 50% attendance in the meetings, and 14 (63.6%) had less than 50% attendance with no activities implemented. The fatality rate decreased in the municipalities that implemented the activities.

  4. Immune Activation and Bacterial Translocation: A Link between Impaired Immune Recovery and Frequent Visceral Leishmaniasis Relapses in HIV-Infected Patients

    Science.gov (United States)

    Machado-de-Assis, Talia S.; Giacoia-Gripp, Carmem; Rabello, Ana; Da-Cruz, Alda M.; Santos-Oliveira, Joanna R.

    2016-01-01

    The maintenance of chronic immune activation due to leishmaniasis or even due to microbial translocation is associated with immunosenescence and may contribute to frequent relapses. Our aim was to investigate whether patients with HIV-associated visceral leishmaniasis (VL/HIV) who experience a single episode of VL have different immunological behaviors in comparison to those who experience frequent relapses. VL/HIV patients were allocated to non-relapsing (NR, n = 6) and relapsing (R, n = 11) groups and were followed from the active phase of VL up to 12 months post-treatment (mpt). The patients were receiving highly active antiretroviral therapy (HAART) and secondary prophylaxis after VL therapy. During active VL, the two groups were similar in all immunological parameters, including the parasite load. At 6 and 12 mpt, the NR group showed a significant gain of CD4+ T cells, a reduction of lymphocyte activation, and lower soluble CD14 and anti-Leishmania IgG3 levels compared to the R group. The viral load remained low, without correlation with the activation. The two groups showed elevated but similar percentages of senescent T cells. These findings suggest a decreased ability of the R group to downmodulate immune activation compared to the NR group. Such functional impairment of the effector response may be a useful indicator for predicting clinical prognosis and recommending starting or stopping secondary prophylaxis. PMID:27907136

  5. Pediatric visceral leishmaniasis in northwest of Iran.

    Science.gov (United States)

    Abdinia, Babak; Oliaei-Motlagh, Mohammad; Teimouri-Dereshki, Amir

    2016-11-01

    Leishmaniasis is one of the major health problems in Iran. Although the incidence of visceral leishmaniasis (VL) is reported almost everywhere, the northwestern Iran is one of the major endemic regions.To do this study, clinical, laboratory as well as disease characteristics of children admitted to Children Cure and Health Hospital, Tabriz University of Medical Sciences, were examined as the reference hospital for the treatment of VL in northwestern Iran.In this study, 156 children hospitalized in a pediatric hospital from 2000 to 2015 for VL were included. Gender, age, anemia, thrombocytopenia, increase in the erythrocyte sedimentation rate (ESR), alanine transaminase (SGPT), and aspartate transaminase (SGOT), major clinical manifestations such as fever, splenomegaly, hepatomegaly, treatment type, and the disease were studied.Among 156 patients examined in this study, 88 (56.41%) and 68 (43.59%) participants were male and female, respectively. The minimum and maximum ages of the infection were 4.5 months and 6 years, respectively. The mean age of the infected children was 17.94 months. Fever (94.24%) and splenomegaly (86.53%) were the most common symptoms of this disease among children. In addition, 49 (31.41%), 64 (41.02%), 18 (11.53%), 33 (21.15%), and 40 (25.64%) participants had leukopenia, hemoglobin count below 8, ESR above 100, ESR above 60, and platelets below 100,000, respectively. Moreover, 39 (25%) and 17 (10.89%) patients had high aspartate transaminase (AST) and alanine transaminase (ALT). Also, 96.2% of the participants responded to the treatment with glucantime. The rate of mortality in this study was 3.2%.Clinically, almost all children had fever and splenomegaly at the onset of the disease. In addition, hepatic involvement was observed in all cases of mortality, cases with a lack of initial response, and those in need of auxiliary medication. Hepatic involvement appears to be related to the prognosis of the disease. In our study, bone marrow

  6. Tuberous sclerosis with visceral leishmaniasis: a case report

    Directory of Open Access Journals (Sweden)

    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.

  7. Hyponatremia in visceral leishmaniasis Hiponatremia no calazar

    Directory of Open Access Journals (Sweden)

    Frederico A. Lima Verde

    2010-10-01

    Full Text Available There are few reports linking hyponatremia and visceral leishmaniasis (kala-azar. This is a study of 55 consecutive kala-azar patients and 20 normal individuals as a control group. Hyponatremia and serum hypo-osmolality were detected in 100% of kala-azar patients. High first morning urine osmolality (750.0 ± 52.0 vs. 894.5 ± 30.0mOsm/kg H2O, p Existem poucos relatos relacionando hiponatremia com a leshmaniose visceral (calazar. Este é um estudo de 55 pacientes portadores de calazar e um grupo controle de 20 indivíduos normais. Hiponatremia e hipo-osmolalidade sérica foram detectados em 100% dos pacientes portadores de calazar. A presença de alta osmolalidade da primeira urina da manhã (750,0 ± 52,0 vs. 894,5 ± 30 mOsm/Kg H2O, p < 0,05 e da urina de 24h (426,0 ± 167,0 vs. 514,6 ± 132,0 mOsm/Kg H2O, p < 0,05, demonstraram a presença de persistente secreção de hormônio antidiurético. A concentração de sódio urinário foi elevada (82,3 ± 44,2 vs. 110,3 ± 34,7 mEq/L, p < 0,05. Hipouricemia ocorreu em 61,8% dos pacientes e aumento da fração de excreção urinária de ácido úrico foi detectada em 74,5% dos casos. Aumento da velocidade de filtração glomerular estava presente em 25,4% dos pacientes. Não havia evidência clínica de depleção de volume extracelular. Valores normais de ADH plasmático foram observados nos pacientes com calazar. Não foi detectada disfunção renal ou endócrina. É provável, que a maioria dos pacientes com calazar apresente uma síndrome de secreção inapropriada de hormônio antidiurético.

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

    Directory of Open Access Journals (Sweden)

    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

  9. Alteration of Fas and Fas ligand expression during human visceral leishmaniasis

    Science.gov (United States)

    Eidsmo, L; Wolday, D; Berhe, N; Sabri, F; Satti, I; El Hassan, A M; Sundar, S; Chiodi, F; Akuffo, H

    2002-01-01

    Several studies in murine systems have suggested a role of apoptosis in the pathogenesis of leishmaniasis. However, the role of apoptosis in visceral leishmaniasis in man has not been explored. In this study, we show that patients with visceral leishmaniasis demonstrate significant dysregulation of Fas and Fas ligand. Levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) were elevated in plasma of patients with active visceral leishmaniasis (VL) and individuals co-infected with VL-HIV-1 compared to healthy controls. The levels of sFas and sFasL were normalized 6 months after successful treatment. In VL patients, the expression of membrane bound Fas, and to a lower extent FasL, were up-regulated on Leishmania donovani-infected spleen cells, the site of parasite multiplication. Expression of Fas and FasL on peripheral blood mononuclear cells was within normal range, probably reflecting that the blood is not a normal site of L. donovani infection. Furthermore, this is suggested by the finding that in vitro infection of macrophages with L. donovani up-regulated Fas expression on the surface of infected cells and enhanced the levels of sFasL in supernatants from infected cultures. How this dysregulation may affect the pathogenesis of human visceral leishmaniasis is discussed. PMID:12390320

  10. Drug resistance in Indian visceral leishmaniasis.

    Science.gov (United States)

    Sundar, S

    2001-11-01

    Throughout the world, pentavalent antimonial compounds (Sb(v)) have been the mainstay of antileishmanial therapy for more than 50 years. Sb(v) has been highly effective in the treatment of Indian visceral leishmaniasis (VL: kala-azar) at a low dose (10 mg/kg) for short durations (6-10 days). But in the early 1980s reports of its ineffectiveness emerged, and the dose of Sb(v) was eventually raised to 20 mg/kg for 30-40 days. This regimen cures most patients with VL except in India, where the proportion of patients unresponsive to Sb(v) has steadily increased. In hyperendemic districts of north Bihar, 50-65% patients fail treatment with Sb(v). Important reasons are rampant use of subtherapeutic doses, incomplete duration of treatment and substandard drugs. In vitro experiments have established emergence of Sb(v) resistant strains of Leishmania donovani, as isolates from unresponsive patients require 3-5 times more Sb(v) to reach similarly effectiveness against the parasite as in Sb(v) responders. Anthroponotic transmission in India has been an important factor in rapid increase in the Sb(v) refractoriness. Pentamidine was the first drug to be used and cured 99% of these refractory patients, but over time even with double the amount of initial doses, it cures only 69-78% patients now and its use has largely been abandoned in India. Despite several disadvantages, amphotericin B is the only drug available for use in these areas and should be used as first-line drug instead of Sb(v). The new oral antileishmanial drug miltefosine is likely to be the first-line drug in future. Unfortunately, development of newer antileishmanial drugs is rare; two promising drugs, aminosidine and sitamaquine, may be developed for use in the treatment of VL. Lipid associated amphotericin B has an excellent safety and efficacy profile, but remains out of reach for most patients because of its high cost.

  11. Management of visceral leishmaniasis with therapeutic vaccines

    Directory of Open Access Journals (Sweden)

    Rawat K

    2016-09-01

    Full Text Available Keerti Rawat,1 Narendra K Yadav,1 Sumit Joshi,1 Sneha Ratnapriya,1 Amogh A Sahasrabuddhe,2 Anuradha Dube1 1Division of Parasitology, 2Division of Molecular and Structural Biology, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow, India Abstract: Visceral leishmaniasis (VL, a phlebotomine-borne neglected tropical disease, is caused by parasites of the Leishmania donovani complex. While L. donovani infection is restricted to the Indian subcontinent and East Africa, where transmission is anthroponotic, Leishmania infantum occurs in Europe, North Africa, and parts of Latin America, where it is zoonotic in nature with dogs as reservoir hosts. Though the incidence of VL caused by L. infantum has been on the decline, L. donovani continues to cause epidemics periodically. By and large, a small proportion of L. donovani infection manifests as clinical disease but majority of the infected individuals remain asymptomatic and contribute to the perpetuation of the VL transmission cycle via the sand fly vector. This is one of the major stumbling blocks to World Health Organization initiatives to eliminate this deadly disease by 2020. These parasites reside within the host macrophages and impair the immune system of the infected individual, which ultimately results in marked immunosuppression. In the absence of any safe and effective vector control measure, attempts have been made to design therapeutic vaccine(s that can exclusively target infected macrophages. So far, two vaccines – a glycoprotein complex from L. donovani promastigote, fucose–mannose ligand with saponin, commercialized as Leishmune®, as well as a polyprotein vaccine formulation, Leish-111f + monophosphoryl lipid A plus squalene emulsion in combination with glucantime, have been successfully evaluated for their immunotherapeutic potential against canine VL. However, encouraging results obtained from several experimental trials so far against human VL

  12. [Visceral leishmaniasis and pregnancy in renal transplanted patient: case report].

    Science.gov (United States)

    Silva, Jaqueline de Almeida; Araújo, Ivan de Melo; Pavanetti, Luiz Carlos; Okamoto, Liene Shigaki; Dias, Mônica

    2015-01-01

    Visceral leishmaniasis (VL) is a severe and potentially fatal disease caused by different Leishmania species, Leishmania chagasi prevailing in Brazil. Main symptoms include fever, malaise, anorexia, weight loss and abdominal enlargement with typically occurring hepatosplenomegaly Currently, VL is considered an opportunistic infection in immunocompromised hosts, including solid organ transplanted patients. The present study reports a case of VL associated to pregnancy after renal transplantation.

  13. Maiden Visit of Visceral Leishmaniasis to Malwa Region

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    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.

  14. Leishmanization revisited: immunization with a naturally attenuated cutaneous Leishmania donovani isolate from Sri Lanka protects against visceral leishmaniasis.

    Science.gov (United States)

    McCall, Laura-Isobel; Zhang, Wen-Wei; Ranasinghe, Shanlindra; Matlashewski, Greg

    2013-02-27

    Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa and associated with three main clinical presentations: cutaneous, mucocutaneous and visceral leishmaniasis. Visceral leishmaniasis is the second most lethal parasitic disease after malaria and there is so far no human vaccine. Leishmania donovani is a causative agent of visceral leishmaniasis in South East Asia and Eastern Africa. However, in Sri Lanka, L. donovani causes mainly cutaneous leishmaniasis, while visceral leishmaniasis is rare. We investigate here the possibility that the cutaneous form of L. donovani can provide immunological protection against the visceral form of the disease, as a potential explanation for why visceral leishmaniasis is rare in Sri Lanka. Subcutaneous immunization with a cutaneous clinical isolate from Sri Lanka was significantly protective against visceral leishmaniasis in BALB/c mice. Protection was associated with a mixed Th1/Th2 response. These results provide a possible rationale for the scarcity of visceral leishmaniasis in Sri Lanka and could guide leishmaniasis vaccine development efforts.

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

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    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

  16. Trace elements in sera from patients with visceral leishmaniasis

    Energy Technology Data Exchange (ETDEWEB)

    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)

  17. RENAL HISTOPATHOLOGICAL FINDINGS IN DOGS WITH VISCERAL LEISHMANIASIS

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    Rosangela Silva Rigo

    2013-04-01

    Full Text Available Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL. Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05 between the presence of glomerulonephritis in symptomatic and oligosymptomatic dogs. The membranous and membranoproliferative glomerulonephritis were the most frequent, both with 18.0% frequency, followed by focal segmental glomerulosclerosis with 14.0%. Changes such as cylindruria, tubular and fibrosis hypertrophy, periglomerular inflammatory infiltrate, and multifocal and diffuse peritubular inflammatory infiltrate were observed. The findings are consistent with those of other authors indicating that renal involvement is common in CVL and the standards of membranous and membranoploriferative glomerulonephritis, as well as the tubulointerstitial involvement, are frequent.

  18. Renal histopathological findings in dogs with visceral leishmaniasis.

    Science.gov (United States)

    Rigo, Rosangela Silva; Carvalho, Cristiano Marcelo Espínola; Honer, Michael Robin; Andrade, Gisele Braziliano de; Silva, Iandara Shetter; Rigo, Leonardo; Figueiredo, Helen Rezende; Barreto, Wanessa Teixeira Gomes

    2013-01-01

    Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL). Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05) between the presence of glomerulonephritis in symptomatic and oligosymptomatic dogs. The membranous and membranoproliferative glomerulonephritis were the most frequent, both with 18.0% frequency, followed by focal segmental glomerulosclerosis with 14.0%. Changes such as cylindruria, tubular and fibrosis hypertrophy, periglomerular inflammatory infiltrate, and multifocal and diffuse peritubular inflammatory infiltrate were observed. The findings are consistent with those of other authors indicating that renal involvement is common in CVL and the standards of membranous and membranoploriferative glomerulonephritis, as well as the tubulointerstitial involvement, are frequent.

  19. Membranoproliferative Glomerulonephritis due to Visceral Leishmaniasis in an HIV Patient

    OpenAIRE

    2015-01-01

    Patient: Male, 47 Final Diagnosis: Membranoproliferative glomerulonephritis Symptoms: Nephrotic syndrome Medication: — Clinical Procedure: Renal biopsy Specialty: Nephrology Objective: Rare disease Background: Visceral leishmaniasis is an important opportunistic disease in HIV-positive patients. The information available on the effects of such co-infection in the kidney is limited. We describe a patient with HIV/leishmania coinfection who developed nephrotic syndrome and membranoproliferative...

  20. Visceral leishmaniasis: immunology and prospects for a vaccine.

    Science.gov (United States)

    Kaye, P M; Aebischer, T

    2011-10-01

    Human visceral leishmaniasis (HVL) is the most severe clinical form of a spectrum of neglected tropical diseases caused by protozoan parasites of the genus Leishmania. Caused mainly by L. donovani and L. infantum/chagasi, HVL accounts for more than 50 000 deaths every year. Drug therapy is available but costly, and resistance against several drug classes has evolved. Here, we review our current understanding of the immunology of HVL and approaches to and the status of vaccine development against this disease.

  1. Liposomal amphotericin B for the treatment of visceral leishmaniasis

    OpenAIRE

    Bern, C.; Adler-Moore, J.; Berenguer, J.; Boelaert, M; van den Boer, M.; Davidson, R N; Figueras, C; Gradoni, L.; Kafetzis, D. A.; Ritmeijer, E.; Rosenthal, E.; Royce, C; Russo, R; Sundar, S; Alvar, J.

    2006-01-01

    During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit ...

  2. Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis

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    Want MY

    2017-03-01

    Full Text Available Muzamil Y Want,1 Mohammad Islammudin,1 Garima Chouhan,1 Hani A Ozbak,2 Hassan A Hemeg,2 Asoke P Chattopadhyay,3 Farhat Afrin2 1Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard, Hamdard University, New Delhi, India; 2Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia; 3Department of Chemistry, University of Kalyani, Kalyani, India Abstract: Visceral leishmaniasis (VL is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA was prepared by thin-film hydration method and optimized using Box–Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a

  3. Oral miltefosine treatment in children with visceral leishmaniasis: a brief review

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    Emilio Palumbo

    2008-02-01

    Full Text Available Visceral leishmaniasis (VL or kala-azar is an infection disease caused by hemiflagellate protozoan parasites (Leishmania donovani and transmitted to humans by the phlebotomine sandfly. Leishmaniasis is distributed worldwide and 13 million people are estimated to be infected, with about 1.8 million new cases each year. All antileishmanial drugs are toxic and most have to be used parenterally for prolonged period. The therapy has been further complicated by large number of infected children and declining effectiveness of pentavalent antimonial compounds. Although the lipid formulations of amphotericin B are an important advance in therapy, their high cost precludes their use. Miltefosine, a phosphocholine analogue originally developed as antimalignant drug, has been found to be highly active against Leishmania in vitro and in animal model. Based on these experiences this drug was tried against human visceral leishmaniasis and found to be highly effective in children. The aim of this review is to evidence the pharmacodymamic and pharmacokinetic characteristics and the safety, tolerance and efficacy of this drug for treatment of visceral leishmaniasis in children.

  4. Treatment of canine Old World visceral leishmaniasis: a systematic review.

    Science.gov (United States)

    Noli, Chiara; Auxilia, Silvia T

    2005-08-01

    Canine visceral leishmaniasis is a systemic disease caused by Leishmania infantum. The aim of this systematic review was to identify and evaluate the evidence of efficacy of interventions for treatment or prevention of canine visceral leishmaniasis, and to propose recommendations for or against their use. Forty-seven articles describing clinical trials published between 1980 and 2004 fulfilled selection criteria. The evaluation of clinical trials provided good evidence for recommending the use of meglumine antimoniate at a minimum dosage of 100 mg kg(-1) daily for at least 3-4 weeks, combined with allopurinol in order to obtain a good clinical efficacy and a reduced relapse rate. The evaluation of the articles also provided fair evidence for recommending the use of pentamidine (4 mg kg(-1) twice weekly) and aminosidine (5 mg kg(-1) twice daily) for 3-4 weeks. There was insufficient evidence for recommending the use of allopurinol alone, amphotericin B, buparvaquone, ketoconazole, enrofloxacin, and the combinations of metronidazole with spiramicyn or metronidazole with enrofloxacin. Fair evidence against the use of aminosidine at high dosages (20-80 mg kg(-1) per day) was proposed due to its side effects. Evaluation of articles on repellent measures against sand fly vectors of leishmaniasis provided good evidence for recommending deltamethrin collars and fair evidence for recommending spot-on permethrin.

  5. Chemotherapy of leishmaniasis: recent advances in the treatment of visceral disease.

    Science.gov (United States)

    Berman, J

    1998-12-01

    New lipid formulations of amphotericin B--AmBisome, Amphotec, and Abelcet--have dramatically decreased the toxicity associated with amphotericin B and have made this group of agents the treatment of choice for visceral leishmaniasis. An agent of a completely different chemical class, the aminoglycoside aminosidine, was 97% curative in India. This agent too may be used for visceral leishmaniasis.

  6. (-)-α-Bisabolol, a Promising Oral Compound for the Treatment of Visceral Leishmaniasis.

    Science.gov (United States)

    Corpas-López, Victoriano; Morillas-Márquez, Francisco; Navarro-Moll, M Concepción; Merino-Espinosa, Gemma; Díaz-Sáez, Victoriano; Martín-Sánchez, Joaquina

    2015-06-26

    The aim of the present study was to assess the in vitro and in vivo activity of (-)-α-bisabolol (1) against the etiological agents of visceral leishmaniasis. Bone-marrow-derived macrophages were infected with Leishmania infantum or L. donovani promastigotes and incubated with (-)-α-bisabolol at different concentrations. Pentamidine isethionate and meglumine antimoniate were used as reference drugs. Inhibitory concentration 50% (IC50) and cytotoxic concentration 50% (CC50) were calculated. Balb/c mice were infected intraperitoneally with stationary-phase promastigotes. They were treated with (-)-α-bisabolol at different doses orally, meglumine antimoniate at 104 mg Sb(V)/kg, or a combination of both. (-)-α-Bisabolol proved to be innocuous to mammal cells and active against L. infantum and L. donovani intracellular amastigotes (IC50 55 and 39 μM, respectively). Compound 1 also proved to be active in an in vivo model of visceral leishmaniasis due to L. infantum, as it reduced parasite load in the spleen and liver by 71.60% and 89.22%, respectively, at 200 mg/kg without showing toxicity. (-)-α-Bisabolol (1) is a nontoxic compound that was proven to be active against visceral leishmaniasis in an in vivo murine model orally. It was more effective than meglumine antimoniate at reducing spleen parasite load and as effective as this antimonial drug in the liver.

  7. Lutzomyia longipalpis in Uruguay: the first report and the potential of visceral leishmaniasis transmission.

    Science.gov (United States)

    Salomón, Oscar Daniel; Basmajdian, Yester; Fernández, María Soledad; Santini, María Soledad

    2011-05-01

    Phlebotomine captures were performed in February 2010 in Salto (Salto department) and Bella Unión-Cuarein (Artigas department), Uruguay. Bella Unión is located across the Paraná River from Monte Caseros, Argentina, where a focus of canine visceral leishmaniasis (VL) was reported in 2009. No VL cases have ever been recorded in Uruguay and the last reported capture of Phlebotominae was in 1932 (Lutzomyia cortelezzii and Lutzomyia gaminarai). Light traps were placed in peridomestic environments, and Lutzomyia longipalpis, the main vector of visceral leishmaniasis, was found in Salto and Bella Unión. This is a first report of an area of potential VL transmission in Uruguay. Active and coordinated surveillance is required immediately the Uruguay-Argentina-Brazil border area.

  8. Intradermal Infection Model for Pathogenesis and Vaccine Studies of Murine Visceral Leishmaniasis

    OpenAIRE

    2003-01-01

    The levels of protection found in vaccine studies of murine visceral leishmaniasis are significantly lower than for cutaneous leishmaniasis; whether this is due to the high-challenge murine model employed and/or is a consequence of differences required in tissue-specific local immune responses is not understood. Consequently, an intradermal murine model of visceral leishmaniasis has been explored. Intradermal inoculation established a chronic infection in susceptible mice which was associated...

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

    Science.gov (United States)

    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

    2016-01-01

    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

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

    Science.gov (United States)

    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%).

  11. Epidemiology of visceral leishmaniasis in Algeria: an update.

    Science.gov (United States)

    Adel, Amel; Boughoufalah, Amel; Saegerman, Claude; De Deken, Redgi; Bouchene, Zahida; Soukehal, Abdelkrim; Berkvens, Dirk; Boelaert, Marleen

    2014-01-01

    Visceral leishmaniasis (VL), a zoonotic disease caused by Leishmania infantum, is endemic in Algeria. This report describes a retrospective epidemiological study conducted on human VL to document the epidemiological profile at national level. All human VL cases notified by the National Institute of Public Health between 1998 and 2008 were investigated. In parallel all VL cases admitted to the university hospitals of Algiers were surveyed to estimate the underreporting ratio. Fifteen hundred and sixty-two human VL cases were reported in Algeria between 1998-2008 with an average annual reported incidence rate of 0.45 cases per 100,000 inhabitants, of which 81.42% were in the age range of 0-4 years. Cases were detected year-round, with a peak notification in May and June. One hundred and seventy patients were admitted to the university hospitals in Algiers in the same period, of which less than one in ten had been officially notified. Splenomegaly, fever, pallor and pancytopenia were the main clinical and laboratory features. Meglumine antimoniate was the first-line therapy for paediatric VL whereas the conventional amphotericin B was used for adult patients. Visceral leishmaniasis in Algeria shows the epidemiological profile of a paediatric disease with a decrease of the annual reported incidence rate. However, vigilance is required because of huge underreporting and an apparent propagation towards the south.

  12. Jaundice in pediatric visceral leishmaniasis (kala-azar)pa-tients

    Institute of Scientific and Technical Information of China (English)

    AKMMamunur Rashid; MdAsrafuzzaman; Abdullah Al Mamun; Abdullah Al Mahboob

    2009-01-01

    Objective:Visceral leishmaniasis (Kala-azar)is endemic in many countries including Bangladesh.Clinical presentation of visceral leishmaniasis in children and adult may vary and at time may simulate many tropical and hepatobiliary diseases.Jaundice and ascites are not common in kala-azar patients.Methods:During the period of January 2005 to December 2006,all the records of the confirmed kala-azar patients presented with jaundice were included in this study.Kala-azar was confirmed by serology test ICT (Immuno Chromatography) and Bone Marrow study.Results:Total 12 kala-azar patients were encountered during this period.Among these twelve cases,presenting features were jaundice (7),splenomegaly (12),hepatomegaly (11)and asci-tes (4).Initial clinical diagnosis of chronic liver disease (CLD)was made in (5),Congenital hemolytic a-naemia in (1)and kala-azar in rest of the patients (6).Common leucopenia and relative lymphocytosis was not observed in any patients.Conclusion:Kala-azar may present with various clinical manifestation in chil-dren and adult.Jaundice can be considered to be a common manifestation particularly in pediatric kala-azar patients.Otherwise,it may mislead to another diagnosis if it is taken as a rare feature in kala-azar.

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

    Directory of Open Access Journals (Sweden)

    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. Therapeutic effect of ursolic acid in experimental visceral leishmaniasis

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    Jéssica A. Jesus

    2017-04-01

    Full Text Available Leishmaniasis is an important neglected tropical disease, affecting more than 12 million people worldwide. The available treatments are not well tolerated and present diverse side effects in patients, justifying the search for new therapeutic compounds. In the present study, the therapeutic potential and toxicity of ursolic acid (UA, isolated from the leaves of Baccharis uncinella C. DC. (Asteraceae, were evaluated in experimental visceral leishmaniasis. To evaluate the therapeutic potential of UA, hamsters infected with L. (L. infantum were treated daily during 15 days with 1.0 or 2.0 mg UA/kg body weight, or with 5.0 mg amphotericin B/kg body weight by intraperitoneal route. Fifteen days after the last dose, the parasitism of the spleen and liver was stimated and the main histopathological alterations were recorded. The proliferation of splenic mononuclear cells was evaluated and IFN-γ, IL-4, and IL-10 gene expressions were analyzed in spleen fragments. The toxicity of UA and amphotericin B were evaluated in healthy golden hamsters by histological analysis and biochemical parameters. Animals treated with UA had less parasites in the spleen and liver when compared with the infected control group, and they also showed preservation of white and red pulps, which correlate with a high rate of proliferation of splenic mononuclear cells, IFN-γ mRNA and iNOS production. Moreover, animals treated with UA did not present alterations in the levels of AST, ALT, creatinine and urea. Taken together, these findings indicate that UA is an interesting natural compound that should be considered for the development of prototype drugs against visceral leishmaniasis.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Visceral Leishmaniasis and HIV coinfection in East Africa.

    Directory of Open Access Journals (Sweden)

    Ermias Diro

    2014-06-01

    Full Text Available Visceral Leishmaniasis (VL is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.

  17. Liposomal amphotericin B for the treatment of visceral leishmaniasis.

    Science.gov (United States)

    Bern, Caryn; Adler-Moore, Jill; Berenguer, Juan; Boelaert, Marleen; den Boer, Margriet; Davidson, Robert N; Figueras, Concepcion; Gradoni, Luigi; Kafetzis, Dimitris A; Ritmeijer, Koert; Rosenthal, Eric; Royce, Catherine; Russo, Rosario; Sundar, Shyam; Alvar, Jorge

    2006-10-01

    During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit groups in East Africa. Clinical trials and experience demonstrate high efficacy and low toxicity for liposomal amphotericin B (total dose, 20 mg/kg) in immunocompetent patients with VL. Combination trials in areas with antileishmanial drug resistance, and treatment and secondary prophylaxis trials in VL-human immunodeficiency virus-coinfected patients, are important to safeguard the current armamentarium and to optimize regimens. The public health community should work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs.

  18. Visceral leishmaniasis due to Leishmania infantum with renal involvement in HIV-infected patients

    OpenAIRE

    Vassallo, Matteo; Moranne, Olivier; Ambrosetti, Damien; Jeandel, Pierre-Yves; Pomares, Christelle; Cassuto, Elisabeth; Boscagli, Annick; Giraud, Guillaume; Montagne, Nathalie; Dentone, Chiara; Demacina, Ilaria; Villaggio, Barbara; Secondo, Giovanni; Ferrea, Giuseppe; Passeron, Corinne

    2014-01-01

    Background We describe histological, clinical findings and outcomes of renal involvement during Leishmania infantum infection in four HIV-infected patients in South France and North Italy hospital settings. Cases presentation Four HIV-infected Caucasian patients (age 24-49) performed renal biopsy during episodes of visceral leishmaniasis. They presented severe immunosuppression, frequent relapses of visceral leishmaniasis during a follow-up period of several years and partial or complete reco...

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

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    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.

  20. Immunotherapy and Immunochemotherapy in Visceral Leishmaniasis: Promising Treatments for this Neglected Disease

    Science.gov (United States)

    Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Coura-Vital, Wendel; Ker, Henrique Gama; Moreira, Nádia das Dores; Vitoriano-Souza, Juliana; Giunchetti, Rodolfo Cordeiro; Carneiro, Cláudia Martins; Reis, Alexandre Barbosa

    2014-01-01

    Leishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; visceral leishmaniasis (VL), 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. Human immunodeficiency virus infection augments the severity of VL increasing the risk of developing active disease by 100–2320 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. PMID:24982655

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

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    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.

  2. 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

    DEFF Research Database (Denmark)

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

    1998-01-01

    Some patients develop post-kala-azar dermal leishmaniasis (PKDL) after they have been treated for the systemic infection kala-azar (visceral leishmaniasis). It has been an enigma why the parasites cause skin symptoms after the patients have been successfully treated for the systemic disease. We...... 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...

  3. TLR4 and NKT cell synergy in immunotherapy against visceral leishmaniasis.

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    Subir Karmakar

    Full Text Available NKT cells play an important role in autoimmune diseases, tumor surveillance, and infectious diseases, providing in most cases protection against infection. NKT cells are reactive to CD1d presented glycolipid antigens. They can modulate immune responses by promoting the secretion of type 1, type 2, or immune regulatory cytokines. Pathogen-derived signals to dendritic cells mediated via Toll like Receptors (TLR can be modulated by activated invariant Natural Killer T (iNKT cells. The terminal β-(1-4-galactose residues of glycans can modulate host responsiveness in a T helper type-1 direction via IFN-γ and TLRs. We have attempted to develop a defined immunotherapeutic, based on the cooperative action of a TLR ligand and iNKT cell using a mouse model of visceral leishmaniasis. We evaluated the anti-Leishmania immune responses and the protective efficacy of the β-(1-4-galactose terminal NKT cell ligand glycosphingophospholipid (GSPL antigen of L. donovani parasites. Our results suggest that TLR4 can function as an upstream sensor for GSPL and provoke intracellular inflammatory signaling necessary for parasite killing. Treatment with GSPL was able to induce a strong effective T cell response that contributed to effective control of acute parasite burden and led to undetectable parasite persistence in the infected animals. These studies for the first time demonstrate the interactions between a TLR ligand and iNKT cell activation in visceral leishmaniasis immunotherapeutic.

  4. Characteristics of bacterial sepsis among patients with visceral leishmaniasis

    Institute of Scientific and Technical Information of China (English)

    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.

  5. Characteristics of bacterial sepsis among patients with visceral leishmaniasis

    Institute of Scientific and Technical Information of China (English)

    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.

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

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    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.

  7. 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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  8. Anti-leishmania antibodies in cerebrospinal fluid from dogs with visceral leishmaniasis

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    V.M.F. Lima

    2003-04-01

    Full Text Available Visceral leishmaniasis in Brazil is caused by Leishmania (Leishmania chagasi and the dog is its most important reservoir. The clinical features in dogs include loss of weight, lymphadenopathy, renal failure, skin lesions, fever, hypergammaglobulinemia, hepatosplenomegaly, anemia, and, rarely, neurological symptoms. Most infected animals develop active disease, characterized by high anti-leishmania antibody titers and depressed lymphoproliferative ability. Antibody production is not primarily important for protection but might be involved in the pathogenesis of tissue lesions. An ELISA test was used to determine if there is an association between neurological symptoms and the presence of anti-L. chagasi antibodies in cerebrospinal fluid (CSF. Thirty serum and CSF samples from symptomatic mixed breed dogs (three with neurological symptoms from a region of high incidence of visceral leishmaniasis in Brazil were examined for antibody using total parasite antigen and anti-dog IgG peroxidase conjugate. A high level of L. chagasi antibodies was observed in sera (mean absorbance ± SD, 1.939 ± 0.405; negative control, N = 20, 0.154 ± 0.074 and CSF (1.571 ± 0.532; negative control, N = 10, 0.0195 ± 0.040 from all animals studied. This observation suggests that L. chagasi can cause breakdown of filtration barriers and the transfer of antibodies and antigens from the blood to the CSF compartment. No correlation was observed between antibody titer in CSF and neurological symptoms.

  9. Recurrent visceral leishmaniasis in a HIV positive patient—a case report

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    Anjo Sunny

    2014-01-01

    Full Text Available Current treatment options for visceral leishmaniasis (kala-azar are pentavalent antimony, amphotericin B, liposomal amphotericin B and miltefosine, which achieve long term clinical relief in the majority of HIV patient. Disease relapse is usually provoked by T-cell number or function impairment (corticosteroid or cytotoxic therapy, transplant recipient, advanced human immunodeficiency virus disease. We report a case of visceral leishmaniasis with multiply relapses in a 45 year old Indian HIV positive man. The disease was diagnosed with rK-39 test and confirmed by spleen aspiration test (presence of Leishmania donovani bodies. These findings demonstrate that human immune deficiency virus-positive with visceral leishmaniasis was caused by dissemination of viscerotropic Leishmania donovani parasites as a consequence of immunosuppression.

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

    Science.gov (United States)

    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.

  11. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis.

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    Rebecca J Faleiro

    2016-02-01

    Full Text Available 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

  12. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis

    Science.gov (United States)

    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. Splenectomy in a patient with treatment-resistant visceral leishmaniasis: a case report

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    Robson Azevedo Dutra

    2012-02-01

    Full Text Available Visceral leishmaniasis (VL, also known as Kala-azar, is a systemic infection caused by a protozoan (Leishmania and, in its classic form, is a serious illness associated with malnutrition, anemia, hepatosplenomegaly, infectious processes and coagulopathies. The effect of splenectomy in patients with visceral leishmaniasis is not well defined; however, it is known that the spleen is the largest reservoir of infected cells belonging to the reticulo endothelial system. Therefore, the surgical procedure is an option for the debulking of parasites, providing a cure for refractory VL and minimizing the complications of hypersplenism.

  14. Leishmaniasis

    DEFF Research Database (Denmark)

    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....... Leishmaniasis can be treated with pentavalent compounds of antimony, but other drugs, including amphotericin B, are also affective. Udgivelsesdato: 2000-Nov-13...

  15. Distribución de vectores de leishmaniasis visceral en la Provincia de Corrientes, 2008 Distribution of vectors of visceral leishmaniasis in the Province of Corrientes, 2008

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    Oscar Daniel Salomón

    2009-12-01

    Full Text Available La leishmaniasis visceral es una parasitosis de importancia en salud pública, producida por Leishmania infantum chagasi. A partir de la urbanización y emergencia en el sur de Brasil y Paraguay, se notificó la presencia del insecto vector Lutzomyia longipalpis en la Argentina; en Formosa, 2004, y en Misiones el primer caso humano en 2006. La notificación de casos de reservorios caninos infectados en la provincia de Corrientes, contigua a Misiones, determinó la búsqueda del vector. Mediante trampeos estandarizados en diciembre del 2008 se capturaron 376 Lu. longipalpis en Ituzaingó, Virasoro, Santo Tomé, Garruchos, Riachuelo, Corrientes y Monte Caseros. Se confirma el riesgo de transmisión vectorial autóctona de leishmaniasis visceral en la provincia de Corrientes. La distribución de vectores en áreas urbanas densamente pobladas, con intenso tránsito de reservorios caninos desde zonas de alta transmisión, y la presencia de reservorios infectados, implica a su vez riesgo epidémico.Visceral leishmaniasis (VL is a relevant parasitic disease in public health, produced by Leishmania infantum chagasi. Since the urbanization and emergence in Southern Brazil and Paraguay, the vector Lutzomyia longipalpis in Formosa, 2004, and the first human visceral leishmaniasis case in Misiones, 2006, have been reported in Argentina. Due to the reports of canine VL, a search of the vector in the Province of Corrientes, contiguous to Misiones, was performed during December 2008. Standarized trapping detected 376 Lu. longipalpis in Ituzaingó, Virasoro, Santo Tomé, Garruchos, Riachuelo, Corrientes and Monte Caseros localities. The risk of autochtonous vectorial transmission was then confirmed in the Province of Corrientes. The distribution of vectors in populated urban areas, with intense transit of canine reservoirs from localities with high transmission, and the existence of infected reservoirs, also implies epidemic risk.

  16. Visceral leishmaniasis and HIV coinfection in Latin America.

    Science.gov (United States)

    Lindoso, José Angelo; Cota, Gláucia Fernandes; da Cruz, Alda Maria; Goto, Hiro; Maia-Elkhoury, Ana Nilce Silveira; Romero, Gustavo Adolfo Sierra; de Sousa-Gomes, Márcia Leite; Santos-Oliveira, Joanna Reis; Rabello, Ana

    2014-09-01

    Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for

  17. Early clinical manifestations associated with death from visceral leishmaniasis.

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    Valdelaine Etelvina Miranda de Araújo

    Full Text Available BACKGROUND: In Brazil, lethality from visceral leishmaniasis (VL is high and few studies have addressed prognostic factors. This historical cohort study was designed to investigate the prognostic factors for death from VL in Belo Horizonte (Brazil. METHODOLOGY: The analysis was based on data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health relating to the clinical manifestations of the disease. During the study period (2002-2009, the SINAN changed platform from a Windows to a Net-version that differed with respect to some of the parameters collected. Multivariate logistic regression models were performed to identify variables associated with death from VL, and these were included in prognostic score. PRINCIPAL FINDINGS: Model 1 (period 2002-2009; 111 deaths from VL and 777 cured patients included the variables present in both SINAN versions, whereas Model 2 (period 2007-2009; 49 deaths from VL and 327 cured patients included variables common to both SINAN versions plus the additional variables included in the Net version. In Model 1, the variables significantly associated with a greater risk of death from VL were weakness (OR 2.9; 95%CI 1.3-6.4, Leishmania-HIV co-infection (OR 2.4; 95%CI 1.2-4.8 and age ≥60 years (OR 2.5; 95%CI 1.5-4.3. In Model 2, the variables were bleeding (OR 3.5; 95%CI 1.2-10.3, other associated infections (OR 3.2; 95%CI 1.3-7.8, jaundice (OR 10.1; 95%CI 3.7-27.2 and age ≥60 years (OR 3.1; 95%CI 1.4-7.1. The prognosis score was developed using the variables associated with death from VL of the latest version of the SINAN (Model 2. The predictive performance of which was evaluated by sensitivity (71.4%, specificity (73.7%, positive and negative predictive values (28.9% and 94.5% and area under the receiver operating characteristic curve (75.6%. CONCLUSIONS: Knowledge regarding the factors associated with death from VL may improve clinical management of patients and contribute to lower

  18. Visceral leishmaniasis and HIV coinfection in Latin America.

    Directory of Open Access Journals (Sweden)

    José Angelo Lindoso

    2014-09-01

    Full Text Available Visceral leishmaniasis (VL is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin

  19. Visceral leishmaniasis in border areas: clustered distribution of phlebotomine sand flies in Clorinda, Argentina

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    Oscar D Salomón

    2009-08-01

    Full Text Available Three years after the first report of Lutzomyia longipalpis in Clorinda, Argentina, a border city near Asunción, Paraguay, the city was surveyed again. Lu. longipalpis was found clustered in the same neighbourhoods in 2007 as in 2004, even though the scattered distribution of canine visceral leishmaniasis was more related to the traffic of dogs through the border.

  20. Visceral leishmaniasis in border areas: clustered distribution of phlebotomine sand flies in Clorinda, Argentina.

    Science.gov (United States)

    Salomón, Oscar D; Quintana, María G; Bruno, Mario R; Quiriconi, Ricardo V; Cabral, Viviana

    2009-08-01

    Three years after the first report of Lutzomyia longipalpis in Clorinda, Argentina, a border city near Asunción, Paraguay, the city was surveyed again. Lu. longipalpis was found clustered in the same neighbourhoods in 2007 as in 2004, even though the scattered distribution of canine visceral leishmaniasis was more related to the traffic of dogs through the border.

  1. Leishmania infection in a population of dogs: an epidemiological investigation relating to visceral leishmaniasis control

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    Klauber Menezes Penaforte

    Full Text Available Identification of factors associated with Leishmaniainfection in dogs is essential for targeting visceral leishmaniasis control actions. Thus, the present study analyzed some of these factors in a population of dogs in a Brazilian municipality, along with the limitations of control strategies implemented there. The association between the exposure variables and occurrences of infection was analyzed through logistic regression models. The disease control interventions were treated qualitatively. Out of the 755 animals examined, 13.6% (103/755 were seropositive. Of these, 23.3% (24/103 were asymptomatic and 76.7% (79/103 presented at least one clinical sign possibly associated with visceral leishmaniasis. With weak associations, purebred, shorthaired, over 5 years of age, male and large dogs were more prone to infection. The latter two variables formed the final regression model and the association with dog size was statistically significant. The control strategies developed presented limitations and a great number of seronegative dogs was culled. The data presented contribute towards better understanding of the dynamics of infection in canine visceral leishmaniasis and indicate that actions aimed towards adequate implementation of Visceral Leishmaniasis control program in Brazilian endemic areas should be prioritized.

  2. Visceral leishmaniasis hos to børn efter ferie i Sydeuropa

    DEFF Research Database (Denmark)

    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...

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

    DEFF Research Database (Denmark)

    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...

  4. Disseminated cutaneous leishmaniasis after visceral disease in a patient with AIDS.

    Science.gov (United States)

    Calza, Leonardo; D'Antuono, Antonietta; Marinacci, Ginevra; Manfredi, Roberto; Colangeli, Vincenzo; Passarini, Beatrice; Orioli, Roberto; Varoli, Ornella; Chiodo, Francesco

    2004-03-01

    Leishmaniasis is emerging as a common and serious opportunistic disease for patients with HIV infection. Almost all cases of HIV-Leishmania coinfection have been described in Mediterranean countries and they occur with various clinical presentations, ranging from typical visceral forms to asymptomatic or atypical cases, including cutaneous and mucocutaneous leishmaniasis. Pentavalent antimony compounds have been the mainstays of antileishmanial therapy for half a century and new lipid formulations of amphotericin B seem reliable, but the most effective treatment remains unknown. We describe a patient who was HIV infected and an intravenous drug user, with an unusual disseminated cutaneous leishmaniasis, after an initial visceral disease and after a 13-month maintenance treatment with liposomal amphotericin. The severe concurrent immunosuppression probably played an essential role in leading to this atypical cutaneous form, characterized by diffuse, nonulcerated, nonscabby maculopapular lesions.

  5. Oral ulcer as an unusual feature of visceral leishmaniasis in an AIDS patient

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    Kumar Pramod

    2007-02-01

    Full Text Available Leishmaniasis, a globally prevalent parasitic disease, occurs in three forms, viz., visceral, cutaneous and mucocutaneous. It is transmitted by female Phlebotomus sandflies. Human immunodeficiency virus (HIV infection is increasing worldwide, and several reports indicate a rising trend of VL / HIV co-infection, modifying the traditional anthroponotic pattern of VL transmission. India is one of the countries having the largest burden of leishmaniasis; nevertheless, there are very few HIV / leishmania co-infection cases reported so far. We report a 35-year-old homemaker infected with the human immunodeficiency virus; she presented with an oral ulcer. The investigations carried out on her revealed that she was afflicted by visceral leishmaniasis, and the oral ulceration was a part of the same. This is only the second such case from the Indian subcontinent, and more significantly from a non-endemic area.

  6. Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions

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    Endalew Yizengaw

    2016-11-01

    Full Text Available Immunologically, active visceral leishmaniasis (VL is characterised by profound immunosuppression, severe systemic inflammatory responses and an impaired capacity to control parasite replication. Neutrophils are highly versatile cells, which play a crucial role in the induction as well as the resolution of inflammation, the control of pathogen replication and the regulation of immune responses. Neutrophil functions have been investigated in human cutaneous leishmaniasis, however, their role in human visceral leishmaniasis is poorly understood.In the present study we evaluated the activation status and effector functions of neutrophils in patients with active VL and after successful anti-leishmanial treatment. Our results show that neutrophils are highly activated and have degranulated; high levels of arginase, myeloperoxidase and elastase, all contained in neutrophils’ granules, were found in the plasma of VL patients. In addition, we show that a large proportion of these cells are immature. We also analysed effector functions of neutrophils that are essential for pathogen clearance and show that neutrophils have an impaired capacity to release neutrophil extracellular traps, produce reactive oxygen species and phagocytose bacterial particles, but not Leishmania parasites.Our results suggest that impaired effector functions, increased activation and immaturity of neutrophils play a key role in the pathogenesis of VL.

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

    DEFF Research Database (Denmark)

    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...... and in 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....

  8. Liposomal amphotericin B in the treatment of visceral leishmaniasis in immunocompetent patients.

    Science.gov (United States)

    Minodier, Philippe; Retornaz, Karine; Horelt, Alexia; Garnier, Jean-Marc

    2003-04-01

    The leishmaniases are protozoan diseases caused by Leishmania parasites. The first-line treatment of its visceral forms is pentavalent antimony (meglumine antimoniate or sodium stibogluconate), but toxicity is frequent with this drug. Moreover antimony unresponsiveness is increasing in Leishmania infantum and L. donovani foci, both in immunocompetent and in immunosuppressed patients. Amphotericin B is a polyene macrolide antibiotic that binds to sterols in cell membranes. It is the most active antileishmanial agent in use. Its infusion-related and renal toxicity may be reduced by lipid-based delivery. Liposomal amphotericin B (AmBisome); Gilead Science, Paris, France) seems to be less toxic than other amphotericin B lipid formulations (Amphocil); Liposome Technology Inc., Menlo Park, CA, USA, Amphotec); Ben Venue Laboratories Inc., Bedford, OH, USA). Optimal drug regimens of AmBisome) vary from one geographical area to another. In the Mediterranean Basin, a total dose of 18 mg/kg (3 mg/kg on days 1-5 and 3 mg/kg on day 10) could be used as first-line treatment of visceral leishmaniasis in immunocompetent patients. In immunocompromised patients, especially those co-infected with HIV, relapses are frequent with AmBisome), as with other drugs.

  9. Dissemination of information on visceral leishmaniasis from schoolchildren to their families: a sustainable model for controlling the disease

    OpenAIRE

    Magalhães,Danielle Ferreira de; Silva,José Ailton da; Haddad, João Paulo Amaral; Moreira,Elvio Carlos; Fonseca,Maria Isabel Magalhães; Ornelas,Marina Lúcia Lima de; Borges,Barbara Kellen Antunes; Luz,Zélia Maria Profeta da

    2009-01-01

    A model for the dissemination of information on visceral leishmaniasis from schoolchildren to their families was evaluated in two schools in Caeté, Minas Gerais State, Brazil. Age ranged from 9 to 17 years in the two schools, one receiving the intervention (with 92 students) and the other serving as the control (96 students). All the students attended a class and received a pamphlet on visceral leishmaniasis. The intervention consisted of a homework assignment in which the student discussed t...

  10. Leishmaniose visceral: estudo retrospectivo de fatores associados à letalidade Visceral leishmaniasis: retrospective study on factors associated with lethality

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    Daniel Gomes de Alvarenga

    2010-04-01

    Full Text Available INTRODUÇÃO: A leishmaniose visceral é um problema de saúde pública, com grau de letalidade alcançando 10%. Para o tratamento medicamentoso, é recomendado o antimoniato de metilglucamina. Este estudo tem como objetivo avaliar o uso de medicamento em casos de leishmaniose visceral atendidos no Serviço de Infectologia do Núcleo de Hospital Universitário de Campo Grande Estado do Mato Grosso do Sul. MÉTODOS: Para coleta de dados, foram pesquisados prontuários de 76 pacientes com diagnóstico de leishmaniose visceral atendidos pelo Serviço de Infectologia do Hospital Universitário de Campo Grande. RESULTADOS: Foram analisados prontuários de 76 (28,9% pacientes (56 homens e 20 mulheres apresentavam comorbidades. Como droga de 1ª escolha, 88,2% dos pacientes utilizaram o antimoniato-N-metil glucamina com evolução para óbito de 18,4%. A análise de sobrevida mostrou diferença estatisticamente significativa em pacientes com e sem comorbidades (pINTRODUCTION: Visceral leishmaniasis is a public health problem, with lethality reaching 10%. The recommended drug treatment is methylglucamine antimoniate. This study aimed to evaluate drug use for cases of visceral leishmaniasis treated at the Infectology Clinic of the Campo Grande University Hospital Center, State of Mato Grosso do Sul. METHODS: To collect data, we examined the medical records of 76 patients with a diagnosis of visceral leishmaniasis treated at this Infectology Clinic. RESULTS: The medical files of 76 patients (56 men and 20 women; 28.9% showed comorbidities. The first choice drug for 88.2% of the patients was N-methylglucamine antimoniate, with a fatal outcome for 18.4%. Survival analysis showed a statistically significant difference between patients with and without comorbidities (p <0.0001 and with comorbidities who used Glucantime® (p < 0.0009. The fatality rate of 18.4% indicates the low efficiency of the healthcare measures used. CONCLUSIONS: The results suggest that

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

    Science.gov (United States)

    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

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

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    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

  13. Visceral leishmaniasis with cardiac involvement in a dog: a case report

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    Goicoa Ana

    2009-04-01

    Full Text Available Abstract A dog presented with cutaneous nodules, enlarged lymph nodes and oedema in limbs, face and abdomen. The diagnosis of visceral leishmaniasis was established by identification of Leishmania amastigotes within macrophages from skin and popliteal lymph node biopsies. At necropsy, lesions were found in different organs, but it was particularly striking to observe large areas of pallor in the myocardium. Histological examination revealed an intense chronic inflammatory reaction in many organs, and numerous macrophages were found to contain amastigote forms of Leishmania. The inflammatory reaction was especially severe in the heart, where large areas of the myocardium appeared infiltrated with huge numbers of mononuclear immune cells, causing cardiac muscle atrophy and degeneration. Despite the severe inflammation, the number of parasitized macrophages was low in the myocardium, as revealed by immunohistochemical staining of Leishmania amastigotes. Because cardiac involvement is not usually described in this condition, this dog represents a very rare case of canine visceral leishmaniasis with affection of the myocardium.

  14. Entomological investigation following the resurgence of human visceral leishmaniasis in southern Algeria.

    Science.gov (United States)

    Benallal, K; Gassen, B; Bouiba, L; Depaquit, J; Harrat, Z

    2013-12-01

    Visceral and cutaneous leishmaniasis are the main endemic vector born diseases in Algeria. In the Hoggar region (extreme south of the country) human visceral leishmaniasis (HVL) is known to be sporadic but during the last decade the number of cases has increased significantly. In 2010, a peak of HVL cases was registered mostly among children. Therefore an entomological survey and a retrospective study on HVL cases were carried out in order to explore the transmission of the disease. Among the sand fly caught Phlebotomus bergeroti was the most frequent species (68%) followed by Sergentomyia schwetzi (22%). In this work we describe the presence of Phlebotomus (Paraphlebotomus) kazeruni for the first time in the Hoggar region.

  15. Treatment options for kala-azar (visceral leishmaniasis) in Bihar, India

    OpenAIRE

    Haaskjold, Astrid Aga

    2005-01-01

    Visceral leishmaniasis (VL) is one of the world s neglected diseases that take a huge toll on people in developing countries, but receive little attention from the Western world. It is a life-threatening disease of great medical, social and economic importance in endemic areas, for which there at present, exists no satisfactory treatment, i.e. affordable and available. VL is a vector-borne disease caused by the protozoa Leishmania donovani. It is a severe debilitating condition, characterised...

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

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    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.

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

    Science.gov (United States)

    Pereira, Mariana R.; Rocha-Silva, Fabiana; Graciele-Melo, Cidiane; Lafuente, Camila R.; Magalhães, Telcia; Caligiorne, Rachel B.

    2014-01-01

    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. PMID:24689047

  18. Morphological Changes in the Bone Marrow of the Dogs with Visceral Leishmaniasis

    OpenAIRE

    Claudia Momo; Ana Paula Prudente Jacintho; Pamela Rodrigues Reina Moreira; Danísio Prado Munari; Gisele Fabrino Machado; Rosemeri Oliveira Vasconcelos

    2014-01-01

    The aim of this study was to evaluate the most frequent lesions in the bone marrow of dogs naturally infected by Leishmania (Leishmania) chagasi. Thirty-three dogs sacrificed at the Zoonosis Control Center of Araçatuba, a municipality endemic for visceral leishmaniasis (VL), were used. The animals were classified as asymptomatic, oligosymptomatic, and symptomatic groups. At the necropsy, bone marrow samples were collected from the femur, fixed, processed, and stained with hematoxylin and eos...

  19. Seroconversion of sentinel chickens as a biomarker for monitoring exposure to visceral Leishmaniasis

    OpenAIRE

    Bárbara Ribeiro Soares; Ana Paula Almeida de Souza; Deboraci Brito Prates; Camila I de Oliveira; Manoel Barral-Netto; José Carlos Miranda; Aldina Barral

    2013-01-01

    Leishmania infantum chagasi causes visceral leishmaniasis (VL); it is transmitted by the sand fly Lutzomyia longipalpis that injects saliva and parasites into the host's skin during a blood meal. Chickens represent an important blood source for sand flies and their presence in the endemic area is often cited as a risk factor for VL transmission. However, the role of chickens in VL epidemiology has not been well defined. Here, we tested if chicken antibodies against Lu. longipalpis salivary gl...

  20. Pediatric visceral leishmaniasis diagnosis in Tunisia: comparative study between optimised PCR assays and parasitological methods

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    Kaouech E.

    2008-06-01

    Full Text Available There has been a steady increase of visceral leishmaniasis during the past 20 years in Tunisia. In this study, we assess the value of two optimised PCR versus those of classical methods for the diagnosis of human visceral leishmaniasis. 106 samples were collected from 53 cases of pediatric visceral leishmaniasis. Peripheral blood and bone marrow samples were analysed both by parasitological methods (direct examination, leukocytoconcentration (LCC and culture and by PCR methods with two primer pair (R221/R332 and Lei 70L/Lei 70R. We diagnosed visceral leishmaniasis in all patients: 44 cases were diagnosed by culture (83%, 42 by direct examination of bone marrow (79%, 17 by LCC (32%, and 53 positive cases with both PCR assays (R221/R332 and/or Lei 70L/Lei 70R (100%. Regarding each PCR assay, for blood samples, the difference between the sensitivities of PCR Lei 70L/Lei 70R (86,8% and PCR R221/R332 (17% is statistically significant with p-value 0.025. For bone marrow, the sensitivities of the two PCR methods were respectively 96,2% (Lei 70L/Lei 70R and 75,5% (R221/R332. On the whole, PCR Lei 70L/Lei 70R was more effective than PCR R221/R332 and conventional methods for the two biological samples. Moreover, the requirement of less invasive sample using blood has the advantage of being repeatable for screening and for post therapeutic monitoring.

  1. Rare splenic complications and specific serology: decisive diagnostic tools in two cases of visceral leishmaniasis

    OpenAIRE

    Andrea Celestini; Federica Paglia; Orlando Dell’ Unto; Riccardo Guarisco; Claudio Puoti

    2012-01-01

    Introduction: Visceral leishmaniasis (VL) is a major endemic vector-borne disease in Southern Europe. We present two cases of VL, both characterized by splenic complications. Methods and results: Case 1: A 47-year-old female presented with effort angina, hepatosplenomegaly and pancytopenia. The clinical course was complicated by splenic infarction. Although bone marrow biopsy failed to show amastigotes, diagnosis was performed by a fast agglutinating screening test (FAST) and confirmed by a d...

  2. Visceral leishmaniasis in renal transplant recipients: successful treatment with liposomal amphotericin B (AmBisome).

    Science.gov (United States)

    Boletis, J N; Pefanis, A; Stathakis, C; Helioti, H; Kostakis, A; Giamarellou, H

    1999-06-01

    Visceral leishmaniasis (VL) is a rare disease in renal transplant recipients. Liposomal amphotericin B (AmBisome) is known to be effective against VL. However, previously there has been no experience with administration of such treatment to renal transplant recipients. We report herein four patients with VL complicating renal transplantation who were treated successfully with liposomal amphotericin B (total dose, 23-40 mg/kg). Neither adverse reactions nor clinical relapses of VL were observed.

  3. Concurrent cutaneous, visceral and ocular leishmaniasis caused by Leishmania (Viannia braziliensis in a kidney transplant patient

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    Gontijo Célia MF

    2002-01-01

    Full Text Available Although cases of leishmaniasis co-infection have been described in acquired immunodeficiency syndrome patients as well as those who have undergone organ transplants, to our knowledge, the present report is the first documented case of simultaneous cutaneous, visceral and ocular leishmaniasis due to Leishmania (Viannia braziliensis in a transplant patient. The patient had been using immunosuppressive drugs since receiving a transplanted kidney. The first clinical signs of leishmaniasis included fever, thoracic pain, hepatosplenomegaly, leucopenia and anemia. The cutaneous disease was revealed by the presence of amastigotes in the skin biopsy. After three months, the patient presented fever with conjunctive hyperemia, intense ocular pain and low visual acuity. Parasites isolated from iliac crest, aqueous humor and vitreous body were examined using a range of molecular techniques. The same strain of L. (V. braziliensis was responsible for the different clinical manifestations. The immunosuppressive drugs probably contributed to the dissemination of Leishmania.

  4. Compartment-specific remodeling of splenic micro-architecture during experimental visceral leishmaniasis.

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    Yurdakul, Pinar; Dalton, Jane; Beattie, Lynette; Brown, Najmeeyah; Erguven, Sibel; Maroof, Asher; Kaye, Paul M

    2011-07-01

    Progressive splenomegaly is a hallmark of visceral leishmaniasis in humans, canids, and rodents. In experimental murine visceral leishmaniasis, splenomegaly is accompanied by pronounced changes in microarchitecture, including expansion of the red pulp vascular system, neovascularization of the white pulp, and remodeling of the stromal cell populations that define the B-cell and T-cell compartments. Here, we show that Ly6C/G(+) (Gr-1(+)) cells, including neutrophils and inflammatory monocytes, accumulate in the splenic red pulp during infection. Cell depletion using monoclonal antibody against either Ly6C/G(+) (Gr-1; RB6) or Ly6G(+) (1A8) cells increased parasite burden. In contrast, depletion of Ly6C/G(+) cells, but not Ly6G(+) cells, halted the progressive remodeling of Meca-32(+) and CD31(+) red pulp vasculature. Strikingly, neither treatment affected white pulp neovascularization or the remodeling of the fibroblastic reticular cell and follicular dendritic cell networks. These findings demonstrate a previously unrecognized compartment-dependent selectivity to the process of splenic vascular remodeling during experimental murine visceral leishmaniasis, attributable to Ly6C(+) inflammatory monocytes.

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

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    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.

  6. Post Kala-Azar Dermal Leishmaniasis following Treatment with 20 mg/kg Liposomal Amphotericin B (Ambisome) for Primary Visceral Leishmaniasis in Bihar, India

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    Sakib Burza; Prabhat Kumar Sinha; Raman Mahajan; Marta González Sanz; María Angeles Lima; Gaurab Mitra; Neena Verma; Pradeep Das

    2014-01-01

    BACKGROUND: The skin disorder Post Kala-Azar Dermal Leishmaniasis (PKDL) occurs in up to 10% of patients treated for visceral leishmaniasis (VL) in India. The pathogenesis of PKDL is not yet fully understood. Cases have been reported in India following therapy with most available treatments, but rarely in those treated with liposomal amphotericin B (Ambisome). Between July 2007 and August 2012 with the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) ...

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

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    Fischer, Dominik; Thomas, Stephanie M; Beierkuhnlein, Carl

    2010-11-01

    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.

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

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    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. Efficacy of Desmodium gangeticum extract and its fractions against experimental visceral leishmaniasis.

    Science.gov (United States)

    Singh, Nasib; Mishra, Pushpesh Kumar; Kapil, Aruna; Arya, Kamal Ram; Maurya, Rakesh; Dube, Anuradha

    2005-04-08

    Crude ethanolic extract of Indian medicinal plant, Desmodium gangeticum (A001) and its three fractions-hexane (F002), n-butanol (F003) and aqueous (F004) were evaluated chemoprophylactically and chemotherapeutically against experimental visceral leishmaniasis in hamsters. Ethanolic extract showed 41.2+/-5.3% inhibition of parasite multiplication when administered at a dose of 250 mg/kgx2 on day -7 and +7 of Leishmania donovani challenge. Its n-butanol fraction exhibited better efficacy than the ethanolic extract to the tune of 66.7+/-6.1% inhibition when administered at similar dose schedule. But the other two fractions failed to exert any action prophylactically. F003 also imparted significant (P<0.001) non-specific resistance to peritoneal macrophages against Leishmania infection. F003 also showed moderate antileishmanial activity when tested against established infection of Leishmania donovani in hamsters but the rest three fractions failed to show any significant inhibition of parasite multiplication. These findings revealed that this plant has potential prophylactic and therapeutic efficacy against Leishmania infection and warrants detailed investigations on its possible immunopotentiatory actions.

  10. Morphological Changes in the Bone Marrow of the Dogs with Visceral Leishmaniasis

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    Claudia Momo

    2014-01-01

    Full Text Available The aim of this study was to evaluate the most frequent lesions in the bone marrow of dogs naturally infected by Leishmania (Leishmania chagasi. Thirty-three dogs sacrificed at the Zoonosis Control Center of Araçatuba, a municipality endemic for visceral leishmaniasis (VL, were used. The animals were classified as asymptomatic, oligosymptomatic, and symptomatic groups. At the necropsy, bone marrow samples were collected from the femur, fixed, processed, and stained with hematoxylin and eosin. The lesion intensity was classified as mild, moderate, or severe. The parasite load was determined using immunohistochemistry. The most important lesions consisted of multifocal to diffuse granulomas, megakaryocytic dysplasia, and medullary aplasia. There were no statistical differences between the three clinical groups regarding parasite load and lesion intensity. Asymptomatic dogs also presented high parasitism in the bone marrow as dogs with clinical signs of VL. It was concluded that, regardless of clinical group, the bone marrow is a site for multiplication of Leishmania chagasi. Possibly, the bone marrow dysplasia may arise from the presence of many parasitized and activated macrophages in this organ. Consequently, it affects the profile of hematopoietic cells in the bone marrow and systemic circulation.

  11. Morphological changes in the bone marrow of the dogs with visceral leishmaniasis.

    Science.gov (United States)

    Momo, Claudia; Jacintho, Ana Paula Prudente; Moreira, Pamela Rodrigues Reina; Munari, Danísio Prado; Machado, Gisele Fabrino; Vasconcelos, Rosemeri de Oliveira

    2014-01-01

    The aim of this study was to evaluate the most frequent lesions in the bone marrow of dogs naturally infected by Leishmania (Leishmania) chagasi. Thirty-three dogs sacrificed at the Zoonosis Control Center of Araçatuba, a municipality endemic for visceral leishmaniasis (VL), were used. The animals were classified as asymptomatic, oligosymptomatic, and symptomatic groups. At the necropsy, bone marrow samples were collected from the femur, fixed, processed, and stained with hematoxylin and eosin. The lesion intensity was classified as mild, moderate, or severe. The parasite load was determined using immunohistochemistry. The most important lesions consisted of multifocal to diffuse granulomas, megakaryocytic dysplasia, and medullary aplasia. There were no statistical differences between the three clinical groups regarding parasite load and lesion intensity. Asymptomatic dogs also presented high parasitism in the bone marrow as dogs with clinical signs of VL. It was concluded that, regardless of clinical group, the bone marrow is a site for multiplication of Leishmania chagasi. Possibly, the bone marrow dysplasia may arise from the presence of many parasitized and activated macrophages in this organ. Consequently, it affects the profile of hematopoietic cells in the bone marrow and systemic circulation.

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

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    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. 

  13. VCAM-1 and ICAM-1 serum levels as markers of relapse in visceral leishmaniasis

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    Alexandros Makis

    2017-01-01

    Full Text Available Objectives-Methods. Visceral leishmaniasis (VL is characterized by chronicity and relapses despite efficacious treatment. Acute and chronic inflammatory processes and concomitant disturbances in cell adhesion characterize the pathogenesis of the disease. To investigate these processes further we measured adhesion molecules (L-selectin, ICAM-1 and VCAM-1 serum levels in 16 children with VL, as well as in 20 healthy controls. All children were treated with liposomal amphotericin B (3 mg/kg on days 1 to 5, 14, and 21. Measurements were performed at days 0, 15 and 30. Results. All children responded well to treatment in both clinical and laboratory terms. In three cases relapse occurred at 3, 5 and 6 months after treatment had ended. Serum L-selectin levels, both pre-treatment and post-treatment, did not significantly differ between patients and controls. VCAM-1 and ICAM-1 median levels were similar in patients and controls (P>0.05 at day 0 and significantly increased at day 15 (P0.05, but not in the 3 patients who relapsed (P<0.05. Conclusions. Despite the small number of the patients, the changes in VCAM-1 and ICAM-1 levels indicate the anti-parasite activation of the immune system during the course of VL and the effect of treatment. Decline in post-treatment serum VCAM-1 and ICAM-1 levels might be used as a marker of treatment efficacy in childhood VL.

  14. Genetically Engineered Ascorbic acid-deficient Live Mutants of Leishmania donovani induce long lasting Protective Immunity against Visceral Leishmaniasis.

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    Anand, Sneha; Madhubala, Rentala

    2015-06-02

    Visceral leishmaniasis caused by Leishmania donovani is the most severe systemic form of the disease. There are still no vaccines available for humans and there are limitations associated with the current therapeutic regimens for leishmaniasis. Recently, we reported functional importance of Arabino-1, 4-lactone oxidase (ALO) enzyme from L. donovani involved in ascorbate biosynthesis pathway. In this study, we have shown that ΔALO parasites do not affect the ability of null mutants to invade visceral organs but severely impair parasite persistence beyond 16 week in BALB/c mice and hence are safe as an immunogen. Both short term (5 week) and long term (20 week) immunization with ΔALO parasites conferred sustained protection against virulent challenge in BALB/c mice, activated splenocytes and resulted in induction of pro-inflammatory cytokine response. Protection in immunized mice after challenge correlated with the stimulation of IFN-γ producing CD4(+) and CD8(+) T cells. Antigen-mediated cell immunity correlated with robust nitrite and superoxide generation, macrophage-derived oxidants critical in controlling Leishmania infection. Our data shows that live attenuated ΔALO parasites are safe, induce protective immunity and can provide sustained protection against Leishmania donovani. We further conclude that the parasites attenuated in their anti-oxidative defence mechanism can be exploited as vaccine candidates.

  15. Protection against experimental visceral leishmaniasis by immunostimulation with herbal drugs derived from Withania somnifera and Asparagus racemosus.

    Science.gov (United States)

    Kaur, Sukhbir; Chauhan, Kalpana; Sachdeva, Heena

    2014-10-01

    Visceral leishmaniasis (VL) is a vector-borne parasitic disease targeting tissue macrophages. It is among the most neglected infectious diseases. As available therapeutics for treatment of this disease have many side effects, there is a need for safer alternatives. One of the immunopathological consequences of active visceral leishmaniasis is suppression of protective T-helper (Th)-1 cells and induction of disease-promoting Th-2 cells, and thus the treatment of VL relies on immunomodulation. In the current study, herbal drugs derived as whole-plant extracts of Asparagus racemosus and Withania somnifera were used to treat Leishmania donovani-infected BALB/c mice. Keeping the scenario of immunosuppression during VL in mind, the potential of these drugs in the restoration of murine Th-1-type protective immune responses was evaluated. To investigate the propensity of these drugs to treat VL, liver parasite load, delayed-type hypersensitivity responses and parasite-specific immunoglobulin levels were studied. Various biochemical and haematological tests were also carried out. A positive-control group used the standard drug treatment of sodium stibogluconate. Treatment of infected mice with A. racemosus and W. somnifera in combination at the higher dose of 200 mg (kg body weight)(-1) not only resulted in a successful reduction in parasite load but also generated protective Th1-type immune responses with normalization of biochemical and haematological parameters, suggesting their potential as potent anti-leishmanial agents.

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

    NARCIS (Netherlands)

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

    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. Sandfly fauna in an area endemic for visceral leishmaniasis in Aracaju, State of Sergipe, Northeast Brazil

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    Verónica de Lourdes Sierpe Jeraldo

    2012-06-01

    Full Text Available INTRODUCTION: In recent years, visceral leishmaniasis, a major public health problem, has been spreading from the rural to urban areas in many areas of Brazil, including Aracaju, the capital of the State of Sergipe. However, there are no studies of the sandfly fauna in this municipality or its variation over the year. METHODS: Phlebotomine sandflies were collected from a rural area of Aracaju from September 2007 to July 2009. Modified CDC ultra-violet (UV light traps were used to evaluate sandfly monthly distribution and their presence in the domestic and peridomestic environments. RESULTS: The most abundant species was Lutzomyia longipalpis (90.4% followed by Evandromyia lenti (9.6%. A chicken shed trap site had the highest proportion of L. longipalpis (51.1% and large numbers of L. longipalpis were also collected in the houses closest to the chicken shed. There was a positive correlation between monthly rainfall and L. longipalpis abundance. CONCLUSIONS: Lutzomyia longipalpis is the most abundant species and is probably the main vector of the visceral leishmaniasis agent in the rural area of Aracaju. An increase in L. longipalpis frequency was observed during the rainy season. The peridomicile-intradomicile observations corroborate the importance of chicken sheds for the presence of L. longipalpis in the peridomestic environment. The great numbers of L. longipalpis inside the houses confirm the endophilic behaviour of this species and the possibility of visceral transmission in the intradomicile.

  18. Improvement in clinical signs and cellular immunity of dogs with visceral leishmaniasis using the immunomodulator P-MAPA.

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    Santiago, Maria Emília B; Neto, Luiz Silveira; Alexandre, Eduardo Costa; Munari, Danísio Prado; Andrade, Mariana Macedo C; Somenzari, Marcos Arruda; Ciarlini, Paulo César; de Lima, V M F

    2013-09-01

    This study investigated the immunotherapeutic potential of the protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride immuno-modulator (P-MAPA) on canine visceral leishmaniasis. Twenty mongrel dogs presenting clinical symptoms compatible with leishmaniasis and diagnosis confirmed by the detection of anti-leishmania antibodies were studied. Ten dogs received 15 doses of the immunomodulator (2.0 mg/kg) intramuscularly, and 10 received saline as a placebo. Skin and peripheral blood samples were collected following administration of the immunomodulator. The groups were followed to observe for clinical signals of remission; parasite load in the skin biopsies using real-time PCR, the cytokines IL-2, IL-10 and IFN-γ in the supernatant of peripheral blood mononuclear cells stimulated in vitro with either total promastigote antigen or phytohemagglutinin measured by capture ELISA, and changes in CD4⁺ and CD8⁺ T cell subpopulations evaluated by flow cytometry. Comparison between the groups showed that treatment with the immunomodulator promoted improvement in clinical signs and a significant reduction in parasite load in the skin. In peripheral blood mononuclear cell cultures, supernatants showed a decrease in IL-10 levels and an increase in IL-2 and IFN-γ. An increase in CD8⁺ T cells was observed in peripheral blood. In addition, the in vitro leishmanicidal action of P-MAPA was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and no leishmanicidal activity was detected. These findings suggest that P-MAPA has potential as an immunotherapeutic drug in canine visceral leishmaniasis, since it assists in reestablishing partial immunocompetence of infected dogs.

  19. Leishmaniose visceral no Brasil: quadro atual, desafios e perspectivas Visceral Leishmaniasis in Brazil: current status, challenges and prospects

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    Célia Maria Ferreira Gontijo

    2004-09-01

    Full Text Available No Brasil, a importância da leishmaniose visceral reside não somente na sua alta incidência e ampla distribuição, mas também na possibilidade de assumir formas graves e letais quando associada ao quadro de má nutrição e infecções concomitantes. A crescente urbanização da doença ocorrida nos últimos 20 anos coloca em pauta a discussão das estratégias de controle empregadas. Neste artigo foram analisados os principais aspectos biológicos, ambientais e sociais que influenciaram no processo de expansão e urbanização dos focos da doença. Os métodos disponíveis para o diagnóstico e tratamento não apresentam a eficácia e aplicabilidade desejadas, embora avanços promissores tenham sido alcançados com as pesquisas de novos testes diagnósticos e drogas terapêuticas. As medidas de controle da doença até agora implementadas foram incapazes de eliminar a transmissão e impedir a ocorrência de novas epidemias. É feita uma breve análise destas medidas e dos desafios a serem enfrentados. A prevenção da doença nos cães através da imunoprofilaxia aparece como uma alternativa para o controle. Uma nova vacina para cães, já testada em campo, está sendo industrializada e será comercializada no Brasil a partir de 2004. Apesar da existência de inúmeros estudos sobre a leishmaniose visceral humana e canina, muitas lacunas ainda precisam ser preenchidas.Visceral leishmaniasis has assumed an increasing importance in Brazil due to its high incidence and wide geographical distribution. When associated with malnutrition and co-infections it can prove to be fatal. A notable increase in transmission rates related to urbanization has been observed in the past 20 years. A combination of measures is needed to define new methods for reducing transmission. This paper analyzes the main biological, environmental and social aspects that have influenced the spread and urbanization of the disease. The diagnostic tests and drugs available

  20. Optimal combinations of control strategies and cost-effective analysis for visceral leishmaniasis disease transmission

    Science.gov (United States)

    Biswas, Santanu; Subramanian, Abhishek; ELMojtaba, Ibrahim M.; Chattopadhyay, Joydev; Sarkar, Ram Rup

    2017-01-01

    Visceral leishmaniasis (VL) is a deadly neglected tropical disease that poses a serious problem in various countries all over the world. Implementation of various intervention strategies fail in controlling the spread of this disease due to issues of parasite drug resistance and resistance of sandfly vectors to insecticide sprays. Due to this, policy makers need to develop novel strategies or resort to a combination of multiple intervention strategies to control the spread of the disease. To address this issue, we propose an extensive SIR-type model for anthroponotic visceral leishmaniasis transmission with seasonal fluctuations modeled in the form of periodic sandfly biting rate. Fitting the model for real data reported in South Sudan, we estimate the model parameters and compare the model predictions with known VL cases. Using optimal control theory, we study the effects of popular control strategies namely, drug-based treatment of symptomatic and PKDL-infected individuals, insecticide treated bednets and spray of insecticides on the dynamics of infected human and vector populations. We propose that the strategies remain ineffective in curbing the disease individually, as opposed to the use of optimal combinations of the mentioned strategies. Testing the model for different optimal combinations while considering periodic seasonal fluctuations, we find that the optimal combination of treatment of individuals and insecticide sprays perform well in controlling the disease for the time period of intervention introduced. Performing a cost-effective analysis we identify that the same strategy also proves to be efficacious and cost-effective. Finally, we suggest that our model would be helpful for policy makers to predict the best intervention strategies for specific time periods and their appropriate implementation for elimination of visceral leishmaniasis. PMID:28222162

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

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

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    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.

  3. Development of Leishmania vaccines in the era of visceral leishmaniasis elimination.

    Science.gov (United States)

    Engwerda, Christian R; Matlashewski, Greg

    2015-07-01

    A visceral leishmaniasis (VL) elimination target set for the Indian subcontinent in 2005 is being met in many endemic areas without a vaccine. This begs a question: is a VL vaccine needed if elimination targets can be met with current control programs? Here, we argue that a vaccine will be critical if the success of recent VL control efforts are to be sustained. However, not only do we require a safe and effective vaccine, but we also need to know how this should be used for maximum impact. In particular, identifying appropriate target populations to vaccinate will be crucial.

  4. Pentamidine as secondary prophylaxis for visceral leishmaniasis in the immunocompromised host: report of four cases.

    Science.gov (United States)

    Patel, T A; Lockwood, D N

    2009-09-01

    We report a retrospective and descriptive study of four immunocompromised patients (three with HIV-1 and one with idiopathic CD4+-lymphopenia) with relapsing visceral leishmaniasis seen at the Hospital for Tropical Diseases, London, in whom pentamidine was used as secondary prophylaxis to prevent relapse. Patients experienced between one and four relapses before commencing prophylaxis with subsequent relapse-free periods ranging from 5 to 98 months. Based on these observational data, we recommend large trials to investigate the efficacy of pentamidine over other agents in preventing relapse of VL in the immunocompromised patient.

  5. Prevalence of zoonotic visceral leishmaniasis in dogs in an endemic area of Brazil

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    Danillo de Souza Pimentel

    2015-01-01

    Full Text Available INTRODUCTION: The northeast region of Brazil is endemic for zoonotic visceral leishmaniasis (ZVL. The aim of this study was to determine the prevalence of infection in dogs in Petrolina. METHODS: Blood samples were collected from dogs (n = 600, and bone-marrow biopsy was performed in animals with positive serological test results that presented clinical signs of ZVL. The serological analyses were performed using an enzyme-linked immunosorbent assay (ELISA (S7(rBiogene. RESULTS: Of the 600 dogs tested, 19% (115/600 presented anti-L. infantum chagasi antibodies. CONCLUSIONS: Our data are important because canine infection is an important risk factor for the human disease.

  6. Visceral leishmaniasis in Brazil: rationale and concerns related to reservoir control

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    Guilherme Loureiro Werneck

    2014-10-01

    Full Text Available The control of zoonotic visceral leishmaniasis is a challenge, particularly in Brazil, where the disease has been gradually spreading across the country over the past 30 years. Strategies employed for decreasing the transmission risk are based on the control of vector populations and reservoirs; since humans are considered unnecessary for the maintenance of transmission. Among the adopted strategies in Brazil, the sacrifice of infected dogs is commonly performed and has been the most controversial measure. In the present study, we provide the rationale for the implementation of different control strategies targeted at reservoir populations and highlight the limitations and concerns associated with each of these strategies.

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

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    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.

  8. U.S. Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis.

    Science.gov (United States)

    Meyerhoff, A

    1999-01-01

    In August 1997, AmBisome (liposomal amphotericin B, Nexstar, San Dimas, CA) was the first drug approved for the treatment of visceral leishmaniasis by the U.S. Food and Drug Administration. The growing recognition of emerging and reemerging infections warrants that safe and effective agents to treat such infections be readily available in the United States. The following discussion of the data submitted in support of the New Drug Application for AmBisome for the treatment of visceral leishmaniasis shows the breadth of data from clinical trials that can be appropriate to support approval for drugs to treat tropical diseases.

  9. Biochemical and nutritional evaluation of patients with visceral leishmaniasis before and after treatment with leishmanicidal drugs

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    Mariana Gatto

    2013-12-01

    Full Text Available Introduction Visceral leishmaniasis (VL is caused by the intracellular protozoan Leishmania donovani complex. VL may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. The nutritional status of the patients with VL is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. Changes in lipoproteins and plasma proteins may have major impacts in the host during infection. Thus, our goal was evaluate the serum total cholesterol, high-density lipoprotein (HDL, low-density lipoprotein (LDL, triglycerides, glucose, albumin, globulin and total protein levels, as well as the body composition, of VL patients before and after treatment. Methods Nutritional evaluation was performed using the bioelectrical impedance analysis (BIA to assess body composition. Biochemical data on the serum total cholesterol, HDL, LDL, triglycerides, glucose, albumin, globulin and total protein were collected from the medical charts of the patients. Results BIA indicated that both pre-treatment and post-treatment patients exhibited decreased phase angles compared to the controls, which is indicative of disease. Prior to treatment, the patients exhibited lower levels of total body water compared to the controls. Regarding the biochemical evaluation, patients with active VL exhibited lower levels of total cholesterol, HDL, LDL and albumin and higher triglyceride levels compared to patients after treatment and the controls. Treatment increased the levels of albumin and lipoproteins and decreased the triglyceride levels. Conclusions Our results suggest that patients with active VL present biochemical and nutritional changes that are reversed by treatment.

  10. Glycosylation of erythrocyte spectrin and its modification in visceral leishmaniasis.

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    Sajal Samanta

    Full Text Available Using a lectin, Achatinin-H, having preferential specificity for glycoproteins with terminal 9-O-acetyl sialic acid derivatives linked in α2-6 linkages to subterminal N-acetylgalactosamine, eight distinct disease-associated 9-O-acetylated sialoglycoproteins was purified from erythrocytes of visceral leishmaniaisis (VL patients (RBC(VL. Analyses of tryptic fragments by mass spectrometry led to the identification of two high-molecular weight 9-O-acetylated sialoglycoproteins as human erythrocytic α- and β-spectrin. Total spectrin purified from erythrocytes of VL patients (spectrin(VL was reactive with Achatinin-H. Interestingly, along with two high molecular weight bands corresponding to α- and β-spectrin another low molecular weight 60 kDa band was observed. Total spectrin was also purified from normal human erythrocytes (spectrin(N and insignificant binding with Achatinin-H was demonstrated. Additionally, this 60 kDa fragment was totally absent in spectrin(N. Although the presence of both N- and O-glycosylations was found both in spectrin(N and spectrin(VL, enhanced sialylation was predominantly induced in spectrin(VL. Sialic acids accounted for approximately 1.25 kDa mass of the 60 kDa polypeptide. The demonstration of a few identified sialylated tryptic fragments of α- and β-spectrin(VL confirmed the presence of terminal sialic acids. Molecular modelling studies of spectrin suggest that a sugar moiety can fit into the potential glycosylation sites. Interestingly, highly sialylated spectrin(VL showed decreased binding with spectrin-depleted inside-out membrane vesicles of normal erythrocytes compared to spectrin(N suggesting functional abnormality. Taken together this is the first report of glycosylated eythrocytic spectrin in normal erythrocytes and its enhanced sialylation in RBC(VL. The enhanced sialylation of this cytoskeleton protein is possibly related to the fragmentation of spectrin(VL as evidenced by the presence of an

  11. CANINE VISCERAL LEISHMANIASIS CASE INVESTIGATION IN THE JACARE REGION OF NITEROI, RIO DE JANEIRO, BRAZIL.

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    Oliveira, Amanda Codeço de; Figueiredo, Fabiano Borges; Silva, Valmir Laurentino; Santos, Fernanda Nunes; Souza, Marcos Barbosa de; Madeira, Maria de Fátima; Abrantes, Tuanne Rotti; Périssé, André Reynaldo Santos

    2015-01-01

    American visceral leishmaniasis is a vector-borne zoonosis in expansion in Brazil. Dogs are the main urban reservoir. Departing from a case of canine visceral leishmaniasis (CVL) in Jacaré, Niterói, Rio de Janeiro State, an epidemiological canine and entomological study was performed to assess the extension of the disease at the location. Sample was collected around the case and the dogs identified by serological tests (rapid double platform immunochromatographic exams, immunoenzymatic assay/ELISA, indirect immunofluorescence/IFAT). The parasitological diagnosis was performed in animals positive in at least one of these tests. The entomological study was carried out by using light traps and manual collection. The associations between canine variables and outcome (ELISA and IFAT reagents) were assessed by the chi-square test and adjusted by multivariate logistic regression for those associations with p < 0.1 in the bivariate analysis. Seventeen cases of CVL were detected among 110 evaluated dogs (prevalence of 15.5%). Presence of ectoparasites (OR 6.5; 95% CI 1.1-37.4), animals with clinical signs (OR 9.5; 95% CI 1.2-76.6), and previous cases of CVL in the same house (OR 17.9; 95% CI 2.2-147.1) were associated with the outcome. Lutzomyia longipalpis was not detected. Our results are indicative of an ongoing transmission in the area.

  12. GEOGRAPHICAL EXPANSION OF CANINE VISCERAL LEISHMANIASIS IN RIO DE JANEIRO STATE, BRAZIL

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    da SILVA, Denise Amaro; MADEIRA, Maria de Fátima; FIGUEIREDO, Fabiano Borges

    2015-01-01

    SUMMARY Visceral Leishmaniasis (VL) is a vector-borne disease that affects humans, and domestic and wild animals. It is caused by the protozoan Leishmania (Leishmania) infantum (syn = Leishmania chagasi). The domestic dog (Canis familiaris) is considered the main reservoir of the etiologic agent of VL in domestic and peridomestic environments. In the past three years, although control actions involving domestic dogs are routinely performed in endemic areas of the Rio de Janeiro State, new cases of canine visceral leishmaniasis (CVL) have been reported in several municipalities. The objective of this short communication was to describe the geographical expansion of CVL in the Rio de Janeiro State, Brazil, through its reports in the scientific literature and studies performed by our group. From 2010 to 2013, autochthonous and allochthonous cases of CVL were reported in the municipalities of Mangaratiba, Marica, Niteroi, Barra Mansa, Cachoeiras de Macacu, Volta Redonda, Resende and Rio de Janeiro. These reports demonstrate that CVL is in intense geographical expansion around the state; therefore, a joint effort by public agencies, veterinarians and researchers is needed in order to minimize and/or even prevent the dispersion of this disease. PMID:26603233

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

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    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

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

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    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

    2015-07-14

    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/m(2))] 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/m(2) 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 DDT post-IRS was 0.37 g ai/m(2); 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.

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

    Science.gov (United States)

    Salih, Niven; Elhag, Mousab Siddig; Elbadawi, Mobarak Elnour; Hammam, Omer; Mumina, Ann; Atia, Atia Abdalla; Etard, Jean-François; Ritmeijer, Koert; Chappuis, François

    2015-01-01

    Background 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. Methods 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. Results 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. Discussion and conclusion Although these results do not provide evidence of causality, they provide useful suggestions for guiding further intervention studies on VL preventive measures. PMID:26544177

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

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    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.

  17. Canine visceral leishmaniasis in Iran: A systematic review and meta-analysis.

    Science.gov (United States)

    Shokri, Azar; Fakhar, Mahdi; Teshnizi, Saeed Hosseini

    2017-01-01

    Visceral leishmaniasis is considered an endemic zoonosis in some parts of Iran and dogs are main reservoirs, which play role in the transmission cycle of human leishmaniasis. This systematic review and meta-analysis was performed to determine the prevalence of canine visceral leishmaniasis (CVL) in Iran. Data were systematically collected from 1982 to 2015 in Iran on the following electronic databases: PubMed, Google Scholar, Science Direct, Scopus, Web of Science, Magiran, Irandoc, Iran medex and Scientific Information Database (SID). A total of 39 articles concerning dogs, 6 articles on jackals, 4 articles on wolves and 4 articles on foxes, reporting the prevalence of CVL from different regions of Iran fulfilled our eligibility criteria. Totally, 19903 dogs, 151 jackals, 42 wolves and 44 foxes were examined and the overall prevalence rate of CVL in Iran was estimated to be as following: in dogs 16% (95% CI: 13-19%), in jackals 10% (95% CI: 5-15%), in wolves 10% (95% CI: 5-15%) and in foxes 10% (95% CI: 1k19%), respectively. There was a significant difference in infection rate between male and female dogs, the infection in males 9% (95% CI: 8.8-10.5%) was more than females 7% (95% CI: 5.5-7.5%) (p=0.024). Also, the rate of infection was significantly higher in older dogs than younger ones (pIran. Further investigation and monitoring will be required to improve the surveillance and control strategies to reduce the incidence of CVL in Iran.

  18. Polymerase Chain Reaction in the Diagnosis of Visceral Leishmaniasis Recurrence in the Setting of Negative Splenic Smears.

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    Hasnain, Golam; Basher, Ariful; Nath, Proggananda; Ghosh, Prakash; Hossain, Faria; Hossain, Shakhawat; Mondal, Dinesh

    2016-01-01

    This report presents two cases of visceral leishmaniasis (VL) recurrence where the microscopy of the splenic smear failed in diagnosis. However, a strong clinical suspicion compelled further evaluation by polymerase chain reaction (PCR), which validated the etiology. This short report highlights the usefulness of PCR in diagnosing cases of suspected smear-negative VL recurrence.

  19. Use of miltefosine in the treatment of visceral leishmaniasis in children at a tertiary care hospital of Karachi.

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    Humayun, Khadija Nuzhat; Saleem, Taimur; Khalid, Umair; Jehan, Fyezah; Soofi, Sajid

    2010-06-01

    Existing standard treatment options for visceral leishmaniasis are less than optimal. We report here the use of oral miltefosine in the treatment of two paediatric cases of visceral leishmaniasis at a tertiary care hospital in Karachi, Pakistan. One patient came from Balochistan while the second patient was from Northern Pakistan. Both presented with a prolonged history of fever, massive hepatosplenomegaly, anaemia and thrombocytopenia. Visceral leishmaniasis was diagnosed with bone marrow studies. Amphotericin B was first started in the first patient; however severe hypokalaemia and allergic reaction occurred. Oral miltefosine was then administered. The child showed clinical improvement with regards to signs of leishmania infection but succumbed to a nosocomial infection during the hospital stay. In the second patient, miltefosine was started in the first instance. He showed remarkable clinical improvement. At 2 months follow-up, the child showed adequate weight gain along with successful resolution of hepatosplenomegaly and fever. Miltefosine has the potential to be considered a first line therapy for visceral leishmaniasis in developing countries; however larger studies are warranted to validate the trends observed in this small case series.

  20. Parasite load estimation by qPCR differentiates between asymptomatic and symptomatic infection in Indian Visceral Leishmaniasis

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    Sudarshan, Medhavi; Sundar, Shyam

    2014-01-01

    Using quantitative PCR we differentiated asymptomatic and symptomatic Indian Leishmania donovani infection. qPCR on blood of 40 visceral leishmaniasis, 130 endemic and 40 nonendemic healthy controls showed 500 times less (p<0.0001) parasitemia in asymptomatic compared to the symptomatic ones, and threshold of 5 parasite genome/ml for the clinical disease. PMID:25023070

  1. Dissemination of information on visceral leishmaniasis from schoolchildren to their families: a sustainable model for controlling the disease.

    Science.gov (United States)

    de Magalhães, Danielle Ferreira; da Silva, José Ailton; Haddad, João Paulo Amaral; Moreira, Elvio Carlos; Fonseca, Maria Isabel Magalhães; de Ornelas, Marina Lúcia Lima; Borges, Barbara Kellen Antunes; da Luz, Zélia Maria Profeta

    2009-07-01

    A model for the dissemination of information on visceral leishmaniasis from schoolchildren to their families was evaluated in two schools in Caeté, Minas Gerais State, Brazil. Age ranged from 9 to 17 years in the two schools, one receiving the intervention (with 92 students) and the other serving as the control (96 students). All the students attended a class and received a pamphlet on visceral leishmaniasis. The intervention consisted of a homework assignment in which the student discussed the class content and pamphlet with a family member. Knowledge by family members (n = 100) on visceral leishmaniasis was evaluated with a pre and post-intervention questionnaire applied by a health agent, who also completed a form on hygiene around the household as observed during the home visit. A significant improvement was observed in knowledge and hygiene (e.g., sweeping of leaves, fruit, and branches from the yards) among the families that were exposed to the intervention (p < 0.05). The spread of information on visceral leishmaniasis by schoolchildren can contribute to measures for preventing the disease.

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

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    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.

  3. Infecção bacteriana em pacientes portadores de Leishmaniase visceral Bacterial infection in patients with visceral leishmaniasis

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    Jaqueline Guerreiro

    1985-12-01

    Full Text Available Uma análise retrospectiva de 63 casos de Leishmaniose visceral (L.V. revelou a presença, em 33 deles, de infecção bacteriana associada. Infecções do trato respiratório foram observadas em 13 (39,3% pacientes, comprometimento de pele em 4 (12%, do trato urinário em 4 (12%, do ouvido em 3 (9%, e de orofaringe em 2 (6%. Sete (21% pacientes apresentaram infecção concomitante em múltiplos sítios. Documentação bacteriológica através de isolamneto do agente etiológico foi obtida em 10, não havendo predominância estatisticamente significante de bactérias Gram positivas ou negativas. Houve 9 casos de óbito nestes 63 pacientes, sendo que em 8 deles a infecção bacteriana fazia parte do quadro clínico final. A análise das taxas de globulinas séricas revelou que infecção esteve presente de modo significativo (p 0.05 com relação ao número de neutrófilos entre os grupos com e sem infecção bacteriana. Concluiu-se, portanto, que infecção bacteriana é um achado freqüente em pacientes com L.V. e se constitui num sinal de mau prognóstico da doença.In an analysis of 63 hospitalized cases with visceral leishmaniasis, the clinical or post-mortem diagnosis of bacterial infection was performed in 33; 13 (39.3% patients had respiratory infection, 4 (12.1% had skin infection, 4 had urinary tract infection, 3 (9.0% showed ear infection and 2 (6.6% had infection of the oral cavity. It is worth mentioning that in 7 (21% cases there was infection in multiple sites. Gram positive and/or Gram negative organisms were isolated from 10 patients. In only two (autopsied cases, infection with less common organisms was recorded, one with disseminated candidiasis and another with disseminated tuberculosis. Death occurred in 9 of the 63 cases, and in 8 of these, concomitant bacterial infection of importance was documented. Patients who had serum globulins lower than 4 g% had significantly more infection (p less than 0.05 than patients with

  4. Visceral Leishmaniasis

    Science.gov (United States)

    2011-06-01

    Lymph nodes are painless and seldom greater than 2 cm in diameter. Trophic changes of the skin and hair of 4 Figure 5.6. a,b a. Radiograph of...patients. Pathologic Features In the less common acute VL, the spleen is smooth and friable and splenic follicles are small. Patients with progres- sive...potential for these factors to serve as vaccine targets to prevent pathogen transmission. Parasite Immunol. 2006;28:131-141 12. Magill AJ. Leishmania

  5. Visceral leishmaniasis in a kidney transplant recipient: parasitic interstitial nephritis, a cause of renal dysfunction.

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    Dettwiler, S; McKee, T; Hadaya, K; Chappuis, F; van Delden, C; Moll, S

    2010-06-01

    Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports. In the 61 cases of renal transplant recipients with VL reported in the literature, renal dysfunction was noted at clinical presentation and was more frequently observed as a complication of antiparasitic therapy. However, no pathological analysis of the allograft lesions was reported. We present the case of a Swiss renal transplant recipient who developed VL after vacations in Spain and Tunisia, complicated by acute parasitic nephritis in the renal allograft 3 months after a well-conducted treatment of liposomal amphotericin B.

  6. The first canine visceral leishmaniasis outbreak in Campinas, State of São Paulo Southeastern Brazil

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    Andrea Paula Bruno von Zuben

    2014-06-01

    Full Text Available Introduction Early detection of American visceral leishmaniasis (AVL outbreak in animals is crucial for controlling this disease in non-endemic areas. Methods Epidemiological surveillance (2009-2012 was performed in Campinas, State of São Paulo, Brazil. Results In 2009, Leishmania chagasi was positively identified in four dogs. Entomological research and three serological studies (2010-2012 were undertaken as monitoring measures; these approaches revealed a moderate prevalence of Leishmania present in 4% of the canine population. Nyssomyia whitmani and Lutzomyia longipalpis were the predominant species identified. Conclusions Detection of an AVL outbreak in dogs in an area with an evolving natural landscape containing sand flies is crucial for control programs.

  7. Risk factors for visceral leishmaniasis in a new epidemic site in Amhara Region, Ethiopia.

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    Bashaye, Seife; Nombela, Nohelly; Argaw, Daniel; Mulugeta, Abate; Herrero, Merce; Nieto, Javier; Chicharro, Carmen; Cañavate, Carmen; Aparicio, Pilar; Vélez, Iván Darío; Alvar, Jorge; Bern, Caryn

    2009-07-01

    We conducted a case-control study to evaluate risk factors for visceral leishmaniasis during an epidemic in a previously unaffected district of Ethiopia. We also collected blood and bone marrow specimens from dogs in the outbreak villages. In multivariable analyses of 171 matched case-control pairs, dog ownership, sleeping under an acacia tree during the day, and habitually sleeping outside at night were associated with significantly increased risk. Specimens from 7 (3.8%) dogs were positive by immunofluorescent antibody test (IFAT) and both enzyme-linked immunosorbent assays (ELISAs), whereas Leishmania DNA was detected in 5 (2.8%) bone marrow aspirates (from 3 seropositive and 2 seronegative dogs). Insecticide-treated nets may only protect a portion of those at risk. Further research on the vectors, the role of the dog in the transmission cycle, and the effect of candidate interventions are needed to design the best strategy for control.

  8. The economic value of a visceral leishmaniasis vaccine in Bihar state, India.

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

    2012-03-01

    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 vaccine to be cost-effective (and in many cases economically dominant, i.e., saving costs and providing health benefits) throughout a wide range of vaccination costs and vaccine efficacies, and VL risks. Overall, our study strongly supports the continued development of a VL vaccine.

  9. Analysis of immune responses in dogs with canine visceral leishmaniasis before, and after, drug treatment.

    Science.gov (United States)

    Rhalem, A; Sahibi, H; Lasri, S; Jaffe, C L

    1999-10-01

    The incidence of canine visceral leishmaniasis (CVL) is increasing in the Mediterranean region. Many drugs have been tested for treatment of CVL, but little is known regarding their effect on test immune responses. In our study, three dogs naturally infected with Leishmania infantum and five dogs experimentally infected with the same strain, were treated with dimethasulfonate pentamidine (Lomidine) and the immune response evaluated before, and after, treatment. After the last injection, animals began to gain weight and the major clinical signs disappeared. Antibody titers gradually decreased to low levels, six months after treatment. At the same time, antigen specific lymphoproliferation reappeared in the sampled animals. This study shows that, after treatment, immune cellular responses to leishmanial antigens, involved in protection against Leishmania infection, were established.

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

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    Christina Monerat Toledo-Machado

    2015-01-01

    Full Text Available 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.

  11. Fatal acute pancreatitis in a patient with visceral leishmaniasis during miltefosine treatment

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    K Pandey

    2013-01-01

    Full Text Available Pancreatitis is a known side effect of the once commonly used drug, sodium stibogluconate, for treatment of visceral leishmaniasis (VL. In India, miltefosine has recently been introduced as the first-line drug. Its side effects include loose motions, vomiting, and teratogenicity. We report here a case of a 41-year-old parasitologically confirmed male case of VL, who developed acute pancreatitis during treatment with miltefosine. On the 13 th day of treatment, he presented with abdominal pain and vomiting. The biochemical, hematological, and radiological features were suggestive of acute pancreatitis. The patient was put on conservative treatment for pancreatitis at the specialized center but succumbed to renal failure and septicaemia.

  12. Protein malnutrition impairs the immune response and influences the severity of infection in a hamster model of chronic visceral leishmaniasis.

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    Eugenia Carrillo

    Full Text Available Leishmaniasis remains one of the world's most devastating neglected tropical diseases. It mainly affects developing countries, where it often co-exists with chronic malnutrition, one of the main risk factors for developing the disease. Few studies have been published, however, on the relationship between leishmaniasis progression and malnutrition. The present paper reports the influence of protein malnutrition on the immune response and visceral disease development in adult hamsters infected with Leishmania infantum fed either standard or low protein diets. The low protein diet induced severe malnutrition in these animals, and upon infection with L. infantum 33% had severe visceral leishmaniasis compared to only 8% of animals fed the standard diet. The infected, malnourished animals showed notable leukocyte depletion, mild specific antibody responses, impairment of lymphoproliferation, presence of parasites in blood (16.67% of the hamsters and significant increase of the splenic parasite burden. Animals fed standard diet suffered agranulocytosis and monocytopenia, but showed stronger specific immune responses and had lower parasite loads than their malnourished counterparts. The present results show that protein malnutrition promotes visceral leishmaniasis and provide clues regarding the mechanisms underlying the impairment of the immune system.

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

    Science.gov (United States)

    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.

  14. Factors associated with visceral leishmaniasis in the americas: a systematic review and meta-analysis.

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    Vinícius Silva Belo

    Full Text Available BACKGROUND: Still today, more than 30 years after the beginning of the process of visceral leishmaniasis' urbanization, there is little knowledge about the risk factors for its occurrence, despite their relevance to the control and understanding of disease dynamics. The present study is the first systematic review with meta-analysis about factors associated with Leishmania infantum infection in humans in the Americas. METHODS AND FINDINGS: After searching different databases, consultations to the reference lists of articles and to experts in the field, 51 studies were reviewed. Theoretical discussions or meta-analysis of p-values or of effect sizes were used to pool information about each variable. The Q test and the I(2 statistic were used to assess heterogeneities among the studies. Male sex was associated with visceral leishmaniasis in studies which used the leishmanin skin test for diagnosis and in those where the outcome was the clinical disease; the opposite occurred when serological diagnosis was applied. Younger individuals were less frequently infected than adults, but were more prone to illness. Although with different levels of evidence and of heterogeneity, the presence of dogs at home, higher dog seropositivity in nearby areas, lower socioeconomic status and highly vegetated areas were associated with L. infantum infection. This was not noticed for the presence of chickens in the house and with nutritional status. Susceptibilities to bias and limitations in the analysis and in the description of results were often identified in the studies analyzed. CONCLUSIONS: Results showed the existence of consistent patterns for some of the factors analyzed and should be taken into account in developing more effective and well-targeted control measures. Studies must be conducted in new areas of the continent, with improved methodological quality and prioritizing the investigation of the patterns identified and their causes, as well as variables

  15. Ecology of Lutzomyia longipalpis in an area of visceral leishmaniasis transmission in north-eastern Brazil.

    Science.gov (United States)

    Costa, Pietra Lemos; Dantas-Torres, Filipe; da Silva, Fernando José; Guimarães, Vanessa Cristina Fitipaldi Veloso; Gaudêncio, Kamila; Brandão-Filho, Sinval Pinto

    2013-05-01

    Visceral leishmaniasis is a major public health issue in South America, where the disease is rapidly spreading. Changes in ecology and distribution of the principal vector, Lutzomyia longipalpis are among the factors accounting for the increasing incidence of the disease in this region. However, information about the ecology of L. longipalpis is still incipient, which may directly impair the implementation of effective control programs. Herein, the ecology of L. longipalpis was studied in a focus of visceral leishmaniasis in north-eastern Brazil. From August 2009 to August 2010, phlebotomine sand flies were monthly collected in four localities using CDC light traps (~37 per month) and a lantern-baited Shannon trap with mouth aspirators. A total of 24,226 phlebotomine sand flies were collected with light traps and 375 with mouth aspirators. The most abundant species was L. longipalpis, representing 97.9% of the specimens collected with light traps and 91.5% with the mouth aspirator. Other species (Lutzomyia evandroi, Lutzomyia lenti and Lutzomyia sallesi) were found in low numbers. Most phlebotomine sand flies (94.6%) were collected at chicken coops and corrals. No significant correlation was found between the monthly abundance of phlebotomine sand flies and the monthly averages of temperature, relative humidity or rainfall. However, interestingly enough, 82.4% of L. longipalpis specimens were collected in months when relative humidity surpassed 75%. This study points out that this vector is well adapted to live in different habitats and to different climate conditions. It also suggests that some north-eastern populations of L. longipalpis may be more xerotolerant than southern populations. Further studies to assess the relationship between microclimate and L. longipalpis density in different Brazilian regions are advised.

  16. Sandflies in an urban area of transmission of visceral leishmaniasis in midwest Brazil

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    Dorval Maria Elizabeth Cavalheiros

    2016-01-01

    Full Text Available The phlebotomine fauna of Campo Grande city, capital of Mato Grosso do Sul state in Brazil, an endemic area for visceral leishmaniasis, has been thoroughly investigated, but all the insect collections were undertaken with automatic light traps. The present study sought to investigate the fauna in this city using Shannon and Disney traps, having human beings and hamsters, respectively, as bait. Both types of traps were installed in forest fragment and peridomiciliary areas in the period from 2007 to 2009. The phlebotomine females were analyzed by PCR for Leishmania identification. Lutzomyia longipalpis was the only species collected in the peridomiciles and rendered a total of 574 specimens with a 5.2:1 male:female ratio. A total of eight species were attracted to the two traps (one of each type installed in the forest fragment, including: Bichromomyia flaviscutellata, Evandromyia bourrouli, Evandromyia lenti, Lutzomyia longipalpis, Nyssomyia whitmani, Pintomyia christenseni, Psathyromyia bigeniculata, and Sciopemyia sordellii. A total of 143 specimens were collected, Bi. flaviscutellata accounting for 81% and Lu. longipalpis for 1.4% of them. In one female of Lu. longipalpis collected in a Disney trap installed in a peridomicile, Leishmania (Leishmania infantum DNA was found, thus strengthening the hypothesis that the transmission of leishmaniasis is in fact occurring in the anthropic environment.

  17. Sandflies in an urban area of transmission of visceral leishmaniasis in midwest Brazil

    Science.gov (United States)

    Dorval, Maria Elizabeth Cavalheiros; Oshiro, Elisa Teruya; Brilhante, Andreia Fernandes; Nunes, Vânia Lúcia Brandão; Cristaldo, Geucira; Lima Júnior, Manoel Sebastião Costa; Galati, Eunice Aparecida Bianchi

    2016-01-01

    The phlebotomine fauna of Campo Grande city, capital of Mato Grosso do Sul state in Brazil, an endemic area for visceral leishmaniasis, has been thoroughly investigated, but all the insect collections were undertaken with automatic light traps. The present study sought to investigate the fauna in this city using Shannon and Disney traps, having human beings and hamsters, respectively, as bait. Both types of traps were installed in forest fragment and peridomiciliary areas in the period from 2007 to 2009. The phlebotomine females were analyzed by PCR for Leishmania identification. Lutzomyia longipalpis was the only species collected in the peridomiciles and rendered a total of 574 specimens with a 5.2:1 male:female ratio. A total of eight species were attracted to the two traps (one of each type) installed in the forest fragment, including: Bichromomyia flaviscutellata, Evandromyia bourrouli, Evandromyia lenti, Lutzomyia longipalpis, Nyssomyia whitmani, Pintomyia christenseni, Psathyromyia bigeniculata, and Sciopemyia sordellii. A total of 143 specimens were collected, Bi. flaviscutellata accounting for 81% and Lu. longipalpis for 1.4% of them. In one female of Lu. longipalpis collected in a Disney trap installed in a peridomicile, Leishmania (Leishmania) infantum DNA was found, thus strengthening the hypothesis that the transmission of leishmaniasis is in fact occurring in the anthropic environment. PMID:27593433

  18. Sandflies in an urban area of transmission of visceral leishmaniasis in midwest Brazil.

    Science.gov (United States)

    Dorval, Maria Elizabeth Cavalheiros; Oshiro, Elisa Teruya; Brilhante, Andreia Fernandes; Nunes, Vânia Lúcia Brandão; Cristaldo, Geucira; Lima Júnior, Manoel Sebastião Costa; Galati, Eunice Aparecida Bianchi

    2016-01-01

    The phlebotomine fauna of Campo Grande city, capital of Mato Grosso do Sul state in Brazil, an endemic area for visceral leishmaniasis, has been thoroughly investigated, but all the insect collections were undertaken with automatic light traps. The present study sought to investigate the fauna in this city using Shannon and Disney traps, having human beings and hamsters, respectively, as bait. Both types of traps were installed in forest fragment and peridomiciliary areas in the period from 2007 to 2009. The phlebotomine females were analyzed by PCR for Leishmania identification. Lutzomyia longipalpis was the only species collected in the peridomiciles and rendered a total of 574 specimens with a 5.2:1 male:female ratio. A total of eight species were attracted to the two traps (one of each type) installed in the forest fragment, including: Bichromomyia flaviscutellata, Evandromyia bourrouli, Evandromyia lenti, Lutzomyia longipalpis, Nyssomyia whitmani, Pintomyia christenseni, Psathyromyia bigeniculata, and Sciopemyia sordellii. A total of 143 specimens were collected, Bi. flaviscutellata accounting for 81% and Lu. longipalpis for 1.4% of them. In one female of Lu. longipalpis collected in a Disney trap installed in a peridomicile, Leishmania (Leishmania) infantum DNA was found, thus strengthening the hypothesis that the transmission of leishmaniasis is in fact occurring in the anthropic environment.

  19. Comparison of new diagnostic tools for management of pediatric Mediterranean visceral leishmaniasis.

    Science.gov (United States)

    Cruz, Israel; Chicharro, Carmen; Nieto, Javier; Bailo, Begoña; Cañavate, Carmen; Figueras, María-Concepción; Alvar, Jorge

    2006-07-01

    New techniques are available for diagnosing leishmaniasis, but their efficacy in the identification of pediatric visceral leishmaniasis (VL) has not been compared with that of traditional methods. Blood, bone marrow, and urine samples were taken from 25 children with VL during their first clinical episode, 22 days after the start of treatment with liposomal amphotericin B (3 mg/kg/day on 6 days over a 10-day period), and when a relapse was suspected during follow-up. The results obtained suggest that antibody detection techniques, the antigen detection in urine (KAtex kit), and Leishmania nested PCR (LnPCR) analysis of the blood could be used for diagnosis of the first clinical episode. After treatment, clinical improvement was associated with negativization of Novy-MacNeal-Nicolle culture and microscopy of bone marrow aspirate, KAtex test, and LnPCR blood analysis results. Interestingly, LnPCR analysis of the bone marrow aspirate showed that sterile cure was not achieved in eight patients, two of which suffered a relapse within 10 to 20 weeks. All of the new noninvasive techniques tested showed high diagnostic sensitivity. However, LnPCR analysis of the bone marrow was the most sensitive; this test was able to detect the persistence of parasites and predict potential relapses.

  20. Vaccination with Leishmania histone H1-pulsed dendritic cells confers protection in murine visceral leishmaniasis.

    Science.gov (United States)

    Agallou, Maria; Smirlis, Despina; Soteriadou, Ketty P; Karagouni, Evdokia

    2012-07-20

    Visceral leishmaniasis is the most severe form of leishmaniases affecting millions of people worldwide often resulting in death despite optimal therapy. Thus, there is an urgent need for the development of effective anti-infective vaccine(s). In the present study, we evaluated the prophylactic value of bone marrow-derived dendritic cells (BM-DCs) pulsed with the Leishmania (L.) infantum histone H1. We developed fully mature BM-DCs characterized by enhanced capacity of IL-12 production after ex vivo pulsing with GST-LeishH1. Intravenous administration of these BM-DCs in naive BALB/c mice resulted in antigen-specific spleenocyte proliferation and IgG1 isotype antibody production and conferred protection against experimental challenge with L. infantum independently of CpG oligonucleotides (ODNs) co-administration. Protection was associated with a pronounced enhancement of parasite-specific IFNγ-producing cells and reduction of cells producing IL-10, whereas IL-4 production was comparable in protected and non-protected mice. The polarization of immune responses to Th1 type was further confirmed by the elevation of parasite-specific IgG2a/IgG1 ratio in protected mice. The above data indicate the immunostimulatory capacity of Leishmania histone H1 and further support its exploitation as a candidate protein for vaccine development against leishmaniasis.

  1. Rare splenic complications and specific serology: decisive diagnostic tools in two cases of visceral leishmaniasis

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    Andrea Celestini

    2012-01-01

    Full Text Available Introduction: Visceral leishmaniasis (VL is a major endemic vector-borne disease in Southern Europe. We present two cases of VL, both characterized by splenic complications. Methods and results: Case 1: A 47-year-old female presented with effort angina, hepatosplenomegaly and pancytopenia. The clinical course was complicated by splenic infarction. Although bone marrow biopsy failed to show amastigotes, diagnosis was performed by a fast agglutinating screening test (FAST and confirmed by a direct agglutinating test (DAT. The patient was treated successfully with AmBisome. Case 2: A 22-year-old male who had undergone a splenectomy to treat splenic rupture related to a minor trauma four months earlier presented with fever, nocturnal sweats and weight loss. The lack of pancytopenia was due to the absence of the spleen. The first biopsy did not identify parasites, but because the FAST had been positive, another bone marrow biopsy was performed, which demonstrated leishmaniasis. This patient was treated with the same schedule of AmBisome infusion. Discussion: 1 The clinical presentation of VL can be atypical, 2 splenic complications can characterize this disease, and 3 specific serology may be an important tool to reach a diagnosis.

  2. A Novel Molecular Test to Diagnose Canine Visceral Leishmaniasis at the Point of Care

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    Castellanos-Gonzalez, Alejandro; Saldarriaga, Omar A.; Tartaglino, Lilian; Gacek, Rosana; Temple, Elissa; Sparks, Hayley; Melby, Peter C.; Travi, Bruno L.

    2015-01-01

    Dogs are the principal reservoir hosts of zoonotic visceral leishmaniasis (VL) but current serological methods are not sensitive enough to detect all subclinically infected animals, which is crucial to VL control programs. Polymerase chain reaction (PCR) methods have greater sensitivity but require expensive equipment and trained personnel, impairing its implementation in endemic areas. We developed a diagnostic test that uses isothermal recombinase polymerase amplification (RPA) to detect Leishmania infantum. This method was coupled with lateral flow (LF) reading with the naked eye to be adapted as a point-of-care test. The L. infantum RPA-LF had an analytical sensitivity similar to real time-PCR, detecting DNA of 0.1 parasites spiked in dog blood, which was equivalent to 40 parasites/mL. There was no cross amplification with dog or human DNA or with Leishmania braziliensis, Leishmania amazonensis, or Trypanosoma cruzi. The test also amplified Leishmania donovani strains (N = 7). In a group of clinically normal dogs (N = 30), RPA-LF detected more subclinical infections than rK39 strip test, a standard serological method (50% versus 13.3% positivity, respectively; P = 0.005). Also, RPA-LF detected L. infantum in noninvasive mucosal samples of dogs with a sensitivity comparable to blood samples. This novel molecular test may have a positive impact in leishmaniasis control programs. PMID:26240156

  3. Comparison of New Diagnostic Tools for Management of Pediatric Mediterranean Visceral Leishmaniasis

    Science.gov (United States)

    Cruz, Israel; Chicharro, Carmen; Nieto, Javier; Bailo, Begoña; Cañavate, Carmen; Figueras, María-Concepción; Alvar, Jorge

    2006-01-01

    New techniques are available for diagnosing leishmaniasis, but their efficacy in the identification of pediatric visceral leishmaniasis (VL) has not been compared with that of traditional methods. Blood, bone marrow, and urine samples were taken from 25 children with VL during their first clinical episode, 22 days after the start of treatment with liposomal amphotericin B (3 mg/kg/day on 6 days over a 10-day period), and when a relapse was suspected during follow-up. The results obtained suggest that antibody detection techniques, the antigen detection in urine (KAtex kit), and Leishmania nested PCR (LnPCR) analysis of the blood could be used for diagnosis of the first clinical episode. After treatment, clinical improvement was associated with negativization of Novy-MacNeal-Nicolle culture and microscopy of bone marrow aspirate, KAtex test, and LnPCR blood analysis results. Interestingly, LnPCR analysis of the bone marrow aspirate showed that sterile cure was not achieved in eight patients, two of which suffered a relapse within 10 to 20 weeks. All of the new noninvasive techniques tested showed high diagnostic sensitivity. However, LnPCR analysis of the bone marrow was the most sensitive; this test was able to detect the persistence of parasites and predict potential relapses. PMID:16825347

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

    Science.gov (United States)

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

    2007-02-09

    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.

  5. Intracellular replication-deficient Leishmania donovani induces long lasting protective immunity against visceral leishmaniasis.

    Science.gov (United States)

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Nylen, Susanne; Duncan, Robert; Sacks, David; Nakhasi, Hira L

    2009-08-01

    No vaccine is currently available for visceral leishmaniasis (VL) caused by Leishmania donovani. This study addresses whether a live attenuated centrin gene-deleted L. donovani (LdCen1(-/-)) parasite can persist and be both safe and protective in animals. LdCen1(-/-) has a defect in amastigote replication both in vitro and ex vivo in human macrophages. Safety was shown by the lack of parasites in spleen and liver in susceptible BALB/c mice, immune compromised SCID mice, and human VL model hamsters 10 wk after infection. Mice immunized with LdCen1(-/-) showed early clearance of virulent parasite challenge not seen in mice immunized with heat killed parasites. Upon virulent challenge, the immunized mice displayed in the CD4(+) T cell population a significant increase of single and multiple cytokine (IFN-gamma, IL-2, and TNF) producing cells and IFN-gamma/IL10 ratio. Immunized mice also showed increased IgG2a immunoglobulins and NO production in macrophages. These features indicated a protective Th1-type immune response. The Th1 response correlated with a significantly reduced parasite burden in the spleen and no parasites in the liver compared with naive mice 10 wk post challenge. Protection was observed, when challenged even after 16 wk post immunization, signifying a sustained immunity. Protection by immunization with attenuated parasites was also seen in hamsters. Immunization with LdCen1(-/-) also cross-protected mice against infection with L. braziliensis that causes mucocutaneous leishmaniasis. Results indicate that LdCen1(-/-) can be a safe and effective vaccine candidate against VL as well as mucocutaneous leishmaniasis causing parasites.

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

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    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

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

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    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

  8. Sand Flies of the Subgenus Adlerius (Diptera: Psychodidae in an Endemic Focus of Visceral Leishmaniasis and Introduction of Phlebotomus (Adlerius comatus as a New Record for Iran.

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    Ali Reza Zahraei-Ramazani

    2013-06-01

    Full Text Available Sand flies of subgenus Adlerius has a wide geographical distribution in Iran and are mostly found in wild form in mountainous areas. They are always considered as probable vectors of visceral leishmaniasis. The objective of this study was to determine the Adlerius species and its composition in an endemic focus of zoonotic visceral leishmaniasis in northwest of the country.Sand flies were collected from 6 different areas of Azarbaijan-e-Sharqi Province using sticky paper traps from August to September which is active season for sand flies in this area, in 2009. The flies were mounted and identified. The length of third antennal segments, ascoid, labrum, coxite, surstyle, style, aedeagus, genital filament, genital pump, width of style, and the end of aedeagus were measured and the number of costal hairs group was also counted as the morphological characters.A total of 30 adult sand flies, (26 males and 4 females including Phlebotomus halepensis (46.8%, P. longiductus (13.3%, P. balcanicus (23.3%, P. comatus (3.3%, and Adlerius spp. (13.3% belong to subgenus Adlerius were identified respectively in 6 counties. One P. comatus male was captured in front of a cave located in the hillside of a mountain covered with the vegetation in Varzeqan area.The presence of at least 5 species of the subgenus Adlerius in Azarbaijan-e-Sharqi Province, an endemic focus of zoonotic visceral leishmaniasis in Iran, shows that the risk of parasite transmission among man and reservoir animals is high during the active season of sand flies. P. comatus is a new record for Iran and needs to be added to the list of Iranian phlebotomines of subgenus Adlerius.

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

    Science.gov (United States)

    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.

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

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    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.

  11. Visceral Leishmaniasis in a UK Toddler following a Short Trip to a Popular Holiday Destination in Spain

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    Neda Minakaran

    2014-01-01

    Full Text Available We herein present the case of a 15-month-old with visceral leishmaniasis diagnosed in the UK following a short trip to a popular holiday destination in Spain. Four months after the initial symptoms, the diagnosis was made incidentally on microscopy of a bone marrow biopsy taken for suspected haematological malignancy after the child developed hepatosplenomegaly, pancytopaenia, and Klebsiella pneumoniae septicaemia.

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

    OpenAIRE

    M.A. Oshaghi; N. Maleki Ravasan; E Javadian; Y Rassi

    2009-01-01

    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 o...

  13. Generation of growth arrested Leishmania amastigotes: a tool to develop live attenuated vaccine candidates against visceral leishmaniasis.

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    Selvapandiyan, Angamuthu; Dey, Ranadhir; Gannavaram, Sreenivas; Solanki, Sumit; Salotra, Poonam; Nakhasi, Hira L

    2014-06-30

    Visceral leishmaniasis (VL) is fatal if not treated and is prevalent widely in the tropical and sub-tropical regions of world. VL is caused by the protozoan parasite Leishmania donovani or Leishmania infantum. Although several second generation vaccines have been licensed to protect dogs against VL, there are no effective vaccines against human VL [1]. Since people cured of leishmaniasis develop lifelong protection, development of live attenuated Leishmania parasites as vaccines, which can have controlled infection, may be a close surrogate to leishmanization. This can be achieved by deletion of genes involved in the regulation of growth and/or virulence of the parasite. Such mutant parasites generally do not revert to virulence in animal models even under conditions of induced immune suppression due to complete deletion of the essential gene(s). In the Leishmania life cycle, the intracellular amastigote form is the virulent form and causes disease in the mammalian hosts. We developed centrin gene deleted L. donovani parasites that displayed attenuated growth only in the amastigote stage and were found safe and efficacious against virulent challenge in the experimental animal models. Thus, targeting genes differentially expressed in the amastigote stage would potentially attenuate only the amastigote stage and hence controlled infectivity may be effective in developing immunity. This review lays out the strategies for attenuation of the growth of the amastigote form of Leishmania for use as live vaccine against leishmaniasis, with a focus on visceral leishmaniasis.

  14. Visceral leishmaniasis in Malta—an 18 year paediatric, population based study

    Science.gov (United States)

    Grech, V.; Mizzi, J.; Mangion, M.; Vella, C.

    2000-01-01

    BACKGROUND—Visceral leishmaniasis (VL) is a chronic parasitic infection that infects approximately 400 000 individuals annually, with a predilection towards early childhood.
AIMS—To study the epidemiology of VL in childhood.
METHODS—VL is endemic in Malta, a small archipelago of islands in the centre of the Mediterranean with a total population approaching half a million. Notification of human cases of leishmaniasis is compulsory. Case records of all 81 paediatric patients with VL between 1980 and 1998 were analysed.
RESULTS—The annual incidence of VL declined for all cases of VL, and declined significantly for paediatric cases (p = 0.01). For 1994to 1998, the overall incidence of VL was 0.9 per 100 000 total population and the paediatric incidence was 2.5 per 100 000 population. Median age at presentation was 34 months. Common features at presentation were splenomegaly, hepatomegaly, fever, and pancytopenia with high lymphocyte and monocyte counts. The diagnostic sensitivity of isolated immunofluorescent antibody testing was equivalent to bone marrow aspiration (95%). Blood transfusions for anaemia were required in 93% of patients. Eleven per cent had intercurrent infections. All patients were cured, and were initially treated with intravenous sodium stibogluconate. Defervescence occurred after a median of six days of treatment, and patients continued to be treated on a day case basis. Nine relapsers were retreated with sodium stibogluconate, achieving a cure rate of 94%, but five patients required additional drug therapy. There were no permanent sequelae associated with VL or its treatment.
CONCLUSIONS—The decreased incidence is attributed to the eradication of stray dogs which are the disease reservoir.

 PMID:10799428

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

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    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

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

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    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.

  17. Immunological changes in canine peripheral blood leukocytes triggered by immunization with first or second generation vaccines against canine visceral leishmaniasis.

    Science.gov (United States)

    Araújo, Márcio Sobreira Silva; de Andrade, Renata Aline; Sathler-Avelar, Renato; Magalhães, Camila Paula; Carvalho, Andréa Teixeira; Andrade, Mariléia Chaves; Campolina, Sabrina Sidney; Mello, Maria Norma; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Malaquias, Luiz Cosme Cotta; Rocha, Luciana Morais; Martins-Filho, Olindo Assis

    2011-05-15

    In this study, we summarized the major phenotypic/functional aspects of circulating leukocytes following canine immunization with Leishvaccine and Leishmune®. Our findings showed that Leishvaccine triggered early changes in the innate immunity (neutrophils and eosinophils) with late alterations on monocytes. Conversely, Leishmune(®) induced early phenotypic changes in both, neutrophils and monocytes. Moreover, Leishvaccine triggered mixed activation-related phenotypic changes on T-cells (CD4+ and CD8+ and B-lymphocytes, whereas Leishmune(®) promoted a selective response, mainly associated with CD8+ T-cell activation. Mixed cytokine profile (IFN-γ/IL-4) was observed in Leishvaccine immunized dogs whereas a selective pro-inflammatory pattern (IFN-γ/NO) was induced by Leishmune® vaccination. The distinct immunological profile triggered by Leishvaccine and Leishmune® may be a direct consequence of the distinct biochemical composition of these immunobiological, i.e. complex versus purified Leishmania antigen along with Bacillus Calmette-Guérin (BCG) versus saponin adjuvant. Both immunobiologicals are able to activate phagocytes and CD8+ T-cells and therefore could be considered as a putative vaccines against canine visceral leishmaniasis (CVL).

  18. VCAM-1 and VLA-4 modulate dendritic cell IL-12p40 production in experimental visceral leishmaniasis.

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    Amanda C Stanley

    Full Text Available Vascular cell adhesion molecule-1 (VCAM-1 interacts with its major ligand very late antigen-4 (VLA-4 to mediate cell adhesion and transendothelial migration of leukocytes. We report an important role for VCAM-1/VLA-4 interactions in the generation of immune responses during experimental visceral leishmaniasis caused by Leishmania donovani. Our studies demonstrate that these molecules play no direct role in the recruitment of leukocytes to the infected liver, but instead contribute to IL-12p40-production by splenic CD8(+ dendritic cells (DC. Blockade of VCAM-1/VLA-4 interactions using whole antibody or anti-VCAM-1 Fab' fragments reduced IL-12p40 mRNA accumulation by splenic DC 5 hours after L. donovani infection. This was associated with reduced anti-parasitic CD4(+ T cell activation in the spleen and lowered hepatic IFNgamma, TNF and nitric oxide production by 14 days post infection. Importantly, these effects were associated with enhanced parasite growth in the liver in studies with either anti-VCAM-1 or anti-VLA-4 antibodies. These data indicate a role for VCAM-1 and VLA-4 in DC activation during infectious disease.

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

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    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.

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

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    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.

  1. Molecular Evaluation of a Case of Visceral Leishmaniasis Due to Leishmania tropica in southwestern Iran

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    Bahador SARKARI

    2016-03-01

    Full Text Available We describe a case of visceral leishmaniasis (VL due to Leishmania tropica in a 50-year-old Iranian man lived in a VL-endemic area in southwest of Iran. The patient presented with a 3-month history of fever and splenomegaly. Clinical signs and serological findings were suggestive of VL. Spleen biopsy was taken from the patient and intracellular forms of Leishmania amastigotes was seen in Giemsa stained smears. The patient was treated with pentavalent antimonial compound with complete resolution of his systemic signs and symptoms. DNA was extracted from the microscopic slides of the spleen biopsy and the nagt (N-Acetylglucosamine-1-Phosphate Transferase gene of Leishmania was PCR-amplified. Sequence analysis of the PCR product demonstrated that the case has 99% identity with those of available sequences of L. tropica. Intra-species variation within isolate was 0-0.1%; whereas, inter-species differences of the isolate with those of L. major and L. infantum was significantly higher.

  2. Molecular Evaluation of a Case of Visceral Leishmaniasis Due to Leishmania tropica in Southwestern Iran.

    Science.gov (United States)

    Sarkari, Bahador; Bavarsad Ahmadpour, Niloofar; Moshfe, Abdolali; Hajjaran, Homa

    2016-01-01

    We describe a case of visceral leishmaniasis (VL) due to Leishmania tropica in a 50-year-old Iranian man lived in a VL-endemic area in southwest of Iran. The patient presented with a 3-month history of fever and splenomegaly. Clinical signs and serological findings were suggestive of VL. Spleen biopsy was taken from the patient and intracellular forms of Leishmania amastigotes was seen in Giemsa stained smears. The patient was treated with pentavalent antimonial compound with complete resolution of his systemic signs and symptoms. DNA was extracted from the microscopic slides of the spleen biopsy and the nagt (N-Acetylglucosamine-1-Phosphate Transferase) gene of Leishmania was PCR-amplified. Sequence analysis of the PCR product demonstrated that the case has 99% identity with those of available sequences of L. tropica. Intra-species variation within isolate was 0-0.1%; whereas, inter-species differences of the isolate with those of L. major and L. infantum was significantly higher.

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

    Science.gov (United States)

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

    2016-02-23

    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.

  4. Visceral Leishmaniasis: Advancements in vaccine development via classical and molecular approaches

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    Sumit eJoshi

    2014-08-01

    Full Text Available Visceral Leishmaniasis (VL or kala-azar, a vector-borne protozoan disease, shows endemicity in larger areas of the tropical, subtropical and the Mediterranean countries. WHO report suggested that nearly 500,000 new cases of VL occur annually, including 100,000 cases from India itself. Treatment with available anti-leishmanial drugs are not cost effective, with varied efficacies and higher relapse rate, which poses a major challenge to current kala-azar control program in Indian subcontinent. Therefore, a vaccine against VL is imperative and knowing the fact that recovered individuals developed lifelong immunity against re-infection, it is feasible. Vaccine development program, though time taking, has recently gained momentum with the emergence of omic era i.e. from genomics to immunomics. Classical as well as molecular methodologies has been overtaken with alternative strategies wherein proteomics based knowledge combined with computational techniques (immunoinformatics speed up the identification and detailed characterization of new antigens for potential vaccine candidates. This may eventually help in the designing of polyvalent synthetic and recombinant chimeric vaccines as an effective intervention measures to control the disease in endemic areas. This review focuses on such newer approaches being utilized for vaccine development against VL.

  5. Phlebotominae distribution in Janaúba, an area of transmission for visceral leishmaniasis in Brazil

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    Érika Monteiro Michalsky

    2009-02-01

    Full Text Available In Brazil, visceral leishmaniasis (VL is caused by Leishmania chagasi parasites that are transmitted to man through the bites of infected females of Lutzomyia longipalpis sand flies. In order to evaluate transmission risk and to clarify the epidemiology of this tropical disease, studies focused on the vector and favorable environmental conditions are of fundamental importance. In this work, we surveyed the phlebotomine sand fly fauna in Janaúba, a Brazilian municipality that is endemic for VL. During a two-year period, entomological captures were performed monthly in 15 districts with high, moderate and low profiles of VL transmission. A total of 14,591 phlebotomine sand flies were captured (92% L. longipalpis, with a predominance of males. Most specimens were captured in the peri-domicile setting, although the number of specimens captured in the intra-domicile setting emphasises the anthropophilic behaviour of this insect. The population density of L. longipalpis was modulated by climate variations, particularly with clear increases immediately after the rainy season. However, the pattern of distribution did not coincide with the occurrence of human or canine cases of VL. This suggests that the eco-epidemiology of VL is particular to each area of transmission and must be taken into account during the design of public health control actions.

  6. Phlebotominae distribution in Janaúba, an area of transmission for visceral leishmaniasis in Brazil.

    Science.gov (United States)

    Michalsky, Erika Monteiro; França-Silva, João Carlos; Barata, Ricardo Andrade; Lara e Silva, Fabiana de Oliveira; Loureiro, Angélica Marciano Fernandes; Fortes-Dias, Consuelo Latorre; Dias, Edelberto Santos

    2009-02-01

    In Brazil, visceral leishmaniasis (VL) is caused by Leishmania chagasi parasites that are transmitted to man through the bites of infected females of Lutzomyia longipalpis sand flies. In order to evaluate transmission risk and to clarify the epidemiology of this tropical disease, studies focused on the vector and favorable environmental conditions are of fundamental importance. In this work, we surveyed the phlebotomine sand fly fauna in Janaúba, a Brazilian municipality that is endemic for VL. During a two-year period, entomological captures were performed monthly in 15 districts with high, moderate and low profiles of VL transmission. A total of 14,591 phlebotomine sand flies were captured (92% L. longipalpis), with a predominance of males. Most specimens were captured in the peri-domicile setting, although the number of specimens captured in the intra-domicile setting emphasises the anthropophilic behaviour of this insect. The population density of L. longipalpis was modulated by climate variations, particularly with clear increases immediately after the rainy season. However, the pattern of distribution did not coincide with the occurrence of human or canine cases of VL. This suggests that the eco-epidemiology of VL is particular to each area of transmission and must be taken into account during the design of public health control actions.

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

    Science.gov (United States)

    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.

  8. Morphological changes and parasite load of the adrenal from dogs with visceral leishmaniasis

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    Claudia Momo

    Full Text Available The objective of this study was to analyze morphological changes and parasite loads in the adrenal gland from 45 dogs with visceral leishmaniasis (VL. The animals were from the Zoonosis Control Center of Araçatuba, state of São Paulo, which is an endemic region for the disease. These animals were euthanized due to positive diagnoses of VL. The dogs were classified into asymptomatic, oligosymptomatic and symptomatic groups. The parasite load was determined by immunohistochemistry, using VL-positive dog hyperimmune serum. Nine dogs showed an inflammatory infiltrate composed, predominantly, of plasma cells and macrophages. However, only eight dogs showed macrophages with amastigote forms of the parasite, immunolabeled in the cytoplasm. The medullary and reticular layers were the most affected areas, possibly due to a favorable microenvironment created by hormones in these regions. The density of parasites in the glandular tissue was not associated with clinical signs of VL (P > 0.05. However, the presence of the parasite was always associated with the presence of a granulomatous inflammatory infiltrate. This gland may not be an ideal place for the parasite's multiplication, but the presence of injuries to the glandular tissue could influence the dog's immune system, thus favoring the parasite's survival in the host's different organs.

  9. Morphological changes and parasite load of the adrenal from dogs with visceral leishmaniasis.

    Science.gov (United States)

    Momo, Claudia; Rocha, Nathália Alves de Souza; Moreira, Pamela Rodrigues Reina; Munari, Danísio Prado; Bomfim, Suely Regina Mogami; Rozza, Daniela Bernadete; Vasconcelos, Rosemeri de Oliveira

    2014-03-01

    The objective of this study was to analyze morphological changes and parasite loads in the adrenal gland from 45 dogs with visceral leishmaniasis (VL). The animals were from the Zoonosis Control Center of Araçatuba, state of São Paulo, which is an endemic region for the disease. These animals were euthanized due to positive diagnoses of VL. The dogs were classified into asymptomatic, oligosymptomatic and symptomatic groups. The parasite load was determined by immunohistochemistry, using VL-positive dog hyperimmune serum. Nine dogs showed an inflammatory infiltrate composed, predominantly, of plasma cells and macrophages. However, only eight dogs showed macrophages with amastigote forms of the parasite, immunolabeled in the cytoplasm. The medullary and reticular layers were the most affected areas, possibly due to a favorable microenvironment created by hormones in these regions. The density of parasites in the glandular tissue was not associated with clinical signs of VL (P > 0.05). However, the presence of the parasite was always associated with the presence of a granulomatous inflammatory infiltrate. This gland may not be an ideal place for the parasite's multiplication, but the presence of injuries to the glandular tissue could influence the dog's immune system, thus favoring the parasite's survival in the host's different organs.

  10. Antileishmania Immunological Tests for Asymptomatic Subjects Living in a Visceral Leishmaniasis-Endemic Area in Brazil

    Science.gov (United States)

    Silva, Luciana Almeida; Romero, Héctor Dardo; Nogueira Nascentes, Gabriel Antônio; Costa, Roberto Teodoro; Rodrigues, Virmondes; Prata, Aluízio

    2011-01-01

    The objective of this study was to evaluate the behavior of different tests used for the diagnosis of visceral leishmaniasis (VL) in asymptomatic subjects living in an endemic area. No gold standard is available for the diagnosis of asymptomatic infection with Leishmania. In continuation of a previous study, 1,017 subjects living in a VL-endemic area were clinically reevaluated. Of these, 576 had at least one positive serological test in a first assessment. About 3 years after the first evaluation, none of the subjects had progressed to clinical VL. Among this group, 246 subjects were selected, and five serological tests (enzyme-linked immunosorbent assay p [ELISAp], ELISArK39, ELISArK26, indirect immunofluorescence test [IIFT] using L. amazonensis promastigote antigen, and an immunochromatographic test using rK39 antigen [TRALd]) and the Montenegro skin test (MST) were repeated. There was a significant increase in the number of subjects who tested positive in the MST, IIFT, ELISAp, and ELISArK39 in the second evaluation. For all tests, there were subjects who tested positive in the first evaluation and negative in the second evaluation. A positive result in the serological tests and MST in subjects from the endemic area studied did not indicate a risk of progression to VL and may only be temporary. PMID:21292896

  11. [Comparative study of diagnostic methods for visceral leishmaniasis in dogs from Ilha Solteira, SP].

    Science.gov (United States)

    de Assis, Juliana; de Queiroz, Nina Marí Gual Pimenta; da Silveira, Rita de Cássia Vieira; Nunes, Cáris Maroni; Oliveira, Trícia Maria Ferreira de Sousa; Junior, Antonio Carlos Faconti de Noronha; Neves, Maria Francisca; Machado, Rosangela Zacarias; Buzetti, Wilma Aparecida Starke

    2010-01-01

    The purpose of the present work was a comparative study of diagnostic methods for Canine Visceral Leishmaniasis (CVL) using serological methods, enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent antibody test (IFAT), histochemical (HE) and immunohistochemical (IMHC) tests using spleen, lymph node and liver canine tissues. In addition, Polymerase Chain Reaction (PCR) was done in blood and in tissues in order to compare and confirm no conclusive and negative diagnosis by the methods above. For this study, 34 dogs were divided according to clinical signs in asymptomatic, oligosymptomatic and polisymptomatic Leishmania-infected dogs euthanized by Zoonotic Disease Control Center (CCZ) from Ilha Solteira, SP, Brazil. The positivism indexes of ELISA, IMHC, IFAT and HE were 65.0, 62.0, 56.0 and 56.0%, respectively with the highest numbers of positive dogs in polisymptomatic (92.0%) followed by oligosymptomatic (57.0%) and asymptomatic dogs (12.5%). Furthermore, PCR confirmed the positive results and detected DNA in tissues from 100% of negative dogs and 89.0% suspects raising the animal positivism index up to 97.0%. In conclusion, PCR was the most sensitive and a valuable method for a definitive CVL diagnosis.

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

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    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)

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

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    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.

  14. Photodynamic vaccination of hamsters with inducible suicidal mutants of Leishmania amazonensis elicits immunity against visceral leishmaniasis

    Science.gov (United States)

    Kumari, Shraddha; Samant, Mukesh; Khare, Prashant; Misra, Pragya; Dutta, Sujoy; Kolli, Bala Krishna; Sharma, Sharad; Chang, Kwang Poo; Dube, Anuradha

    2016-01-01

    Leishmania, naturally residing in the phagolysosomes of macrophages, is a suitable carrier for vaccine delivery. Genetic complementation of these trypanosomatid protozoa to partially rectify their defective heme-biosynthesis renders them inducible with δ-aminolevulinate to develop porphyria for selective photolysis, leaving infected host-cells unscathed. Delivery of released “vaccines” to antigen-presenting cells is thus expected to enhance immune response, while their self-destruction presents added advantages of safety. Such suicidal-L. amazonensis was found to confer immunoprophylaxis and immunotherapy on hamsters against L. donovani. Neither heat-killed nor live parasites without suicidal induction were effective. Photodynamic vaccination of hamsters with the suicidal-mutants reduced the parasite loads by 99% and suppressed the development of disease. These suppressions were accompanied by an increase in Leishmania-specific delayed-type hypersensitivity and lymphoproliferation as well as in the levels of splenic iNOS, IFN-γ and IL-12 expressions and of Leishmania-specific IgG2 in the serum. Moreover, a single intravenous administration of T-cells from vaccinated hamsters was shown to confer on naïve animals an effective cellular immunity against L. donovani challenges. The absence of lesion development at vaccination sites and parasites in the draining lymphnodes, spleen and liver further indicates that the suicidal mutants provide a safe platform for vaccine delivery against experimental visceral leishmaniasis. PMID:19053149

  15. Experimental Infection of Dogs with Leishmania and Saliva as a Model to Study Canine Visceral Leishmaniasis

    Science.gov (United States)

    Costa, Dirceu Joaquim; Carvalho, Rayssa M. de Araujo; Abbehusen, Melissa; Teixeira, Clarissa; Pitombo, Maiana; Trigo, Joelma; Nascimento, Flávia; Amorim, Lucilene; Abreu-Silva, Ana Lucia; do Socorro Pires Cruz, Maria; Miranda, José Carlos; Fukutani, Kyoshi; de Oliveira, Camila I.; Barral, Aldina; Barral-Netto, Manoel; Brodskyn, Cláudia

    2013-01-01

    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 1×107 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 3,35×105 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. PMID:23577121

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

    Science.gov (United States)

    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.

  17. Current challenges in treatment options for visceral leishmaniasis in India: a public health perspective

    Institute of Scientific and Technical Information of China (English)

    Om Prakash Singh; Bhawana Singh; Jaya Chakravarty; Shyam Sundar

    2016-01-01

    Visceral leishmaniasis (VL) is a serious parasitic disease causing considerable mortality and major disability in the Indian subcontinent.It is most neglected tropical disease,particularly in terms of new drug development for the lack of financial returns.An elimination campaign has been running in India since 2005 that aim to reduce the incidence of VL to below 1 per 10,000 people at sub-district level.One of the major components in this endeavor is reducing transmission through early case detection followed by complete treatment.Substantial progress has been made during the recent years in the area of VL treatment,and the VL elimination initiatives have already saved many lives by deploying them effectively in the endemic areas.However,many challenges remain to be overcome including availability of drugs,cost of treatment (drugs and hospitalization),efficacy,adverse effects,and growing parasite resistance.Therefore,better emphasis on implementation research is urgently needed to determine how best to deliver existing interventions with available anti-leishmanial drugs.It is essential that the new treatment options become truly accessible,not simply available in endemic areas so that they may promote healing and save lives.In this review,we highlight the recent advancement and challenges in current treatment options for VL in disease endemic area,and discuss the possible strategies to improve the therapeutic outcome.

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

    Science.gov (United States)

    Pouladfar, Gholamreza; Jafarpour, Zahra; Pourabbas, Bahman; Geramizadeh, Bita; Dashti, Anahita Sanaei

    2016-01-01

    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. PMID:27418985

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

    Science.gov (United States)

    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

  20. American Visceral Leishmaniasis: Factors Associated with Lethality in the State of São Paulo, Brazil

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    Geraldine Madalosso

    2012-01-01

    Full Text Available Objectives. To identify factors associated with death in visceral leishmaniasis (VL cases. Patients and Methodology. We evaluated prognostic factors for death from VL in São Paulo state, Brazil, from 1999 to 2005. A prognostic study nested in a clinical cohort was carried out by data analysis of 376 medical files. A comparison between VL fatal cases and survivors was performed for clinical, laboratory, and biological features. Association between variables and death was assessed by univariate analysis, and the multiple logistic regression model was used to determine adjusted odds ratio for death, controlling confounding factors. Results. Data analysis identified 53 fatal cases out of 376 patients, between 1999 and 2005 in São Paulo state. Lethality was 14.1% (53/376, being higher in patients older than fifty years. The main causes of death were sepsis, bleeding, liver failure, and cardiotoxicity due to treatment. Variables significantly associated with death were severe anemia, bleeding, heart failure, jaundice, diarrhea, fever for more than sixty days, age older than fifty years, and antibiotic use. Conclusion. Educational health measures are needed for the general population and continuing education programs for health professionals working in the affected areas with the purpose of identifying and treating early cases, thus preventing the disease evolution towards death.

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

    Science.gov (United States)

    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.

  2. Two cases of visceral leishmaniasis in Colombia resistant to meglumine antimonial treatment.

    Science.gov (United States)

    Vélez, Iván Darío; Colmenares, Lina María; Muñoz, Carlos Aguirre

    2009-01-01

    Visceral leishmaniasis (VL) affects over 500,000 people worldwide each year. The disease occurs in the Mediterranean basin, Central and South America and is caused by Leishmania infantum (syn L. chagasi). VL is an endemic disease in Colombia, particularly along the Caribbean coast and the Magdalena River Valley and 90% of VL cases occur in children under the age of five. The first line of treatment is chemotherapy with pentavalent antimonial compounds, including sodium stibogluconate (Pentostam) and meglumine antimoniate (Glucantime). These compounds are the ones most used in Colombia, at a dose of 20 mg/kg/day for 28 days. Nevertheless resistance of L. infantum to pentavalent antimonials is becoming an important problem. No cases of VL resistant to pentavalent antimonial compounds have previously been reported from Colombia. This report describes the two cases of VL resistance to antimonial compounds in a girl and a boy who did not respond to previous treatment with Pentacarinat and Glucantime regimens but were treated successfully with liposomal amphotericin B. Based on our findings, we recommend liposomal amphotericin B as the first line of treatment for VL due to its low toxicity, shorter administration period and the low price obtained by WHO.

  3. Forty years of visceral leishmaniasis in the State of Piaui: a review

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    Karina Oliveira Drumond

    2011-02-01

    Full Text Available Visceral leishmaniasis (VL has been known to occur in the state of Piauí since 1934. The typically rural disease began to appear in urban areas over time, being concentrated mainly in Teresina, the capital of Piauí. Teresina was also affected by the first urban epidemic of VL in Brazil. Over 1,000 cases of the disease were reported during urbanization (1981-1986. Human population growth and migration led to land occupation on the outskirts of Teresina. These factors have contributed to vector proliferation, increasing the incidence of VL. At present, the incidence of human and canine disease is quite high and uncontrolled in Piauí. It seems that some measures, such as the elimination of seropositive dogs, failed to significantly reduce the number of new VL cases in Teresina. Despite previously conducted studies, little is known about VL epidemiology in urban areas. The aim of this review is to reveal the situation of VL in Teresina during the last 40 years, focusing on the major factors that may contribute to the high incidence and persistence of VL infection.

  4. Current challenges in treatment options for visceral leishmaniasis in India: a public health perspective.

    Science.gov (United States)

    Singh, Om Prakash; Singh, Bhawana; Chakravarty, Jaya; Sundar, Shyam

    2016-03-08

    Visceral leishmaniasis (VL) is a serious parasitic disease causing considerable mortality and major disability in the Indian subcontinent. It is most neglected tropical disease, particularly in terms of new drug development for the lack of financial returns. An elimination campaign has been running in India since 2005 that aim to reduce the incidence of VL to below 1 per 10,000 people at sub-district level. One of the major components in this endeavor is reducing transmission through early case detection followed by complete treatment. Substantial progress has been made during the recent years in the area of VL treatment, and the VL elimination initiatives have already saved many lives by deploying them effectively in the endemic areas. However, many challenges remain to be overcome including availability of drugs, cost of treatment (drugs and hospitalization), efficacy, adverse effects, and growing parasite resistance. Therefore, better emphasis on implementation research is urgently needed to determine how best to deliver existing interventions with available anti-leishmanial drugs. It is essential that the new treatment options become truly accessible, not simply available in endemic areas so that they may promote healing and save lives. In this review, we highlight the recent advancement and challenges in current treatment options for VL in disease endemic area, and discuss the possible strategies to improve the therapeutic outcome.

  5. Epidemiology of Visceral Leishmaniasis in a Reemerging Focus of Intense Transmission in Minas Gerais State, Brazil

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    Ricardo Andrade Barata

    2013-01-01

    Full Text Available This study was developed in the urban area of Governador Valadares, a reemerging focus of intense transmission of visceral leishmaniasis (VL in Brazil, presenting 86 human cases of VL from 2008 to 2011. The disease prevailed in males (73.2% with most patients between 0 and 9 years (44.1% and a lethality rate of 16.2%. A canine survey was carried out on 16,529 domestic dogs in 35 districts in the area and it showed that 30.2% of them (4,992 dogs were positive for VL by serum assays. Prevalence ratios for canine VL varied between 13.6% and 53.4%. The clinical exam of 343 seropositive dogs showed that 49.9% of them were considered symptomatic, with larger prevalence of canine VL being in short-furred animals (90%. The entomological survey was performed in eight districts, where 2,539 phlebotomines were captured, preferentially in the peridomicile (84.5%. Lutzomyia longipalpis was the predominant species (90% suggesting its participation in the VL transmission in the area. The correlation between canine prevalence and L. longipalpis density was evaluated.

  6. Sandflies (Psychodidae: Phlebotominae) survey in an urban transmission area of visceral leishmaniasis, Northeastern Brazil.

    Science.gov (United States)

    Amóra, Sthenia Santos Albano; Bevilaqua, Claudia Maria Leal; Feijó, Francisco Marlon Carneiro; Oliveira, Paula Gabriela Melo de; Peixoto, Gislayne Christianne Xavier; Sousa, Raimundo Nonato de; Alves, Nilza Dutra; Oliveira, Lorena Mayana Beserra de; Macedo, Iara Térsia Freitas

    2010-01-01

    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.

  7. Seasonal abundance of Lutzomyia longipalpis (Diptera: Psychodidae) at an endemic focus of visceral leishmaniasis in Colombia.

    Science.gov (United States)

    Morrison, A C; Ferro, C; Pardo, R; Torres, M; Devlin, B; Wilson, M L; Tesh, R B

    1995-07-01

    Ecological studies on the sand fly Lutzomyia longipalpis (Lutz & Neiva) were conducted during 1990-1993 in a small rural community in Colombia where American visceral leishmaniasis is endemic. Standardized weekly sand fly collections made from pigpens and natural resting sites displayed a bimodal annual abundance cycle, with a small peak occurring in October-November and a larger one in April-May. Time series analysis was employed to quantify the associations between sand fly abundance and weather factors (temperature, relative humidity, and rainfall). In addition to a prominent 6-mo cycle. Fourier analysis of the collection data demonstrated that the L. longipalpis population also exhibited a 5- to 8-wk cycle that may represent the length of larval development. Autoregressive moving average models were fit to weekly collection data and their residuals were regressed against rainfall, temperature, and relative humidity. A significant positive association between female L. longipalpis abundance and the relative humidity and rainfall recorded 3 wk earlier was found, indicating that these factors may be of value in predicting sand fly abundance. Additionally, these data indicated that L. longipalpis larvae may become quiescent during adverse conditions.

  8. QBC® for the diagnosis of human and canine american visceral leishmaniasis: preliminary data

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    Liarte Daniel B.

    2001-01-01

    Full Text Available "Quantitative Buffy Coat" (QBC® is a direct and fast fluorescent method used for the identification of blood parasites. Since Leishmania chagasi circulates in blood, we decided to test it in American visceral leishmaniasis (AVL. Bone marrow (BM and peripheral blood (PB of 49 persons and PB of 31 dogs were analyzed. QBC® was positive in BM of 11/11 patients with AVL and in 1/6 patients with other diseases. Amastigotes were identified in PB of 18/22 patients with AVL and in none without AVL. The test was positive in 30 out of the 31 seropositive dogs and in 28/28 dogs with Leishmania identified in other tissues. QBC® is a promising method for diagnosis of human AVL, and possibly for the exam of PB of patients with AVL/AIDS, for the control of the cure and for the identification of asymptomatic carriers. Because it is fast and easy to collect and execute, QBC® should be evaluated for programs of reservoir control.

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

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    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.

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

    Science.gov (United States)

    ABRANTES, Tuanne Rotti; MADEIRA, Maria de Fátima; da SILVA, Denise Amaro; PERIÉ, Carolina dos Santos F. S.; V. MENDES, Artur Augusto; MENEZES, Rodrigo Caldas; SILVA, Valmir Laurentino; FIGUEIREDO, Fabiano Borges

    2016-01-01

    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. PMID:26910449

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

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    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.

  12. Description of six autochthonous cases of canine visceral leishmaniasis diagnosed in Pedregulho (São Paulo, Brazil

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    Cássia Regina de Abreu

    Full Text Available Visceral leishmaniasis is an infectious disease of chronic, emerging and zoonotic nature that presents various degrees of severity. In Brazil, this illness is caused by Leishmania infantum (Leishmania chagasi, which is transmitted by the bite of the sand fly Lutzomyia longipalpis, and dogs are its main reservoir. Given the increasing spread of this disease across Brazil, the aim of this study was to report on six cases of canine visceral leishmaniasis, diagnosed in June 2013, in the city of Pedregulho, State of São Paulo, considered to be a non-endemic area and free of phlebotomine sand flies. The diagnosis was based on clinical signs of the patients and additional tests (serological and parasitological. It was concluded that the diagnosis of leishmaniasis is complex because the clinical signs are similar to other systemic diseases, thus justifying the importance of parasitological test of bone marrow, considered "gold standard", in the confirmation of the disease. In addition, the area was not, until now, considered risk place, despite notification.

  13. Recombinant Leishmania tarentolae expressing the A2 virulence gene as a novel candidate vaccine against visceral leishmaniasis.

    Science.gov (United States)

    Mizbani, Amir; Taheri, Tahereh; Zahedifard, Farnaz; Taslimi, Yasaman; Azizi, Hiva; Azadmanesh, Kayhan; Papadopoulou, Barbara; Rafati, Sima

    2009-12-10

    Visceral leishmaniasis is the most severe form of leishmaniasis. To date, there is no effective vaccine against this disease. Many antigens have been examined so far as protein- or DNA-based vaccines, but none of them conferred complete long-term protection. The use of live attenuated vaccines has recently emerged as a promising vaccination strategy. In this study, we stably expressed the Leishmania donovani A2 antigen in Leishmania tarentolae, a non-pathogenic member of the genus Leishmania, and evaluated its protective efficacy as a live vaccine against L. infantum challenge. Our results show that a single intraperitoneal administration of the A2-recombinant L. tarentolae strain protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-gamma production prior and after challenge. This is accompanied by reduced levels of IL-5 production after challenge, leading to a potent Th1 immune response. In contrast, intravenous injection elicited a Th2 type response, characterized by higher levels of IL-5 and high humoral immune response, resulting in a less efficient protection. All together, these results indicate the promise of A2-expressing L. tarentolae as a safe live vaccine against visceral leishmaniasis.

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

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    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

  15. Protective efficacy of antioxidants on cisplatin-induced tissue damage caused in Leishmania donovani infected BALB/c mice against murine visceral leishmaniasis

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    Meenakshi Sharma

    2013-06-01

    Full Text Available Objective: Therapeutic interventions against visceral leishmaniasis (VL are limited and facing serious concerns of toxicity, high cost and emerging resistance, there is a greater interest in new drug developments which are cost effective, efficient and easily available to people suffering from leishmaniasis. Cisplatin (cis-diamminedichloroplatinum II; CDDP has been found to have antileishmanial activity in vitro and in vivo which lead towards an apoptosis like cell death of both promastigotes and amastigotes and a significant reduction in parasite load and enhanced DTH responses which suggested the generation of protective cell-mediated immune responses. But, at higher doses it causes nephrotoxicity-a major side effect. The present study was designed to evaluate the protective efficacy of antioxidants on cisplatin induced tissue damage in Leishmania donovani infected BALB/c mice. Materials and methods: L. donovani infected and uninfected animals were treated with higher doses (5 and 2.5 mg/kg body weight of cisplatin alone and in combination with antioxidants (vitamin C, vitamin E and silibinin for 5 days. Mice were examined for the protective effects of antioxidants on cisplatin indiced tissue damage by DNA fragmentation and histological studies of kidneys, liver and spleen. Results: The damage caused by cisplatin was ameliorated after the supplementation of antioxidants showing a marked reduction in the extent of tubular damage, the focal reaction changes in liver were reversed and no signs of toxicity in the spleen were reported. Moreover, no DNA damage was observed in animals treated with cisplatin along with various antioxidants. Conclusion: The present results showed that antioxidants helped in the amelioration of drug induced toxic effects against murine visceral leishmaniasis, making the combination a potential anti-leishmanial therapy. [J Interdiscipl Histopathol 2013; 1(3.000: 121-136

  16. Low CXCL13 expression, splenic lymphoid tissue atrophy and germinal center disruption in severe canine visceral leishmaniasis.

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    Joselli S Silva

    Full Text Available Visceral leishmaniasis is associated with atrophy and histological disorganization of splenic compartments. In this paper, we compared organized and disorganized splenic lymphoid tissue from dogs naturally infected with Leishmania infantum assessing the size of the white pulp compartments, the distribution of T, B and S100+ dendritic cells, using immunohistochemistry and morphometry and the expression of CCR7 and the cytokines, CXCL13, lymphotoxin (LT-α, LT-β, CCL19, CCL21, TNF-α, IL-10, IFN-γ and TGF-β, using by real time RT-PCR. The lymphoid follicles and marginal zones were smaller (3.2 and 1.9 times, respectively; Mann-Whitney, P<0.02 in animals with disorganized splenic tissue in comparison to those with organized splenic lymphoid tissue. In spleens with disorganized lymphoid tissue, the numbers of T cells and S100+ dendritic cells were decreased in the follicles, and the numbers of B cells were reduced in both the follicles and marginal zones. CXCL13 mRNA expression was lower in animals with disorganized lymphoid tissue (0.5±0.4 compared to those with organized lymphoid tissue (2.7±2.9, both relative to 18S expression, P = 0.01. These changes in the spleen were associated with higher frequency of severe disease (7/12 in the animals with disorganized than in animals with organized (2/13, Chi-square, P = 0.01 splenic lymphoid tissue. The data presented herein suggest that natural infection with Leishmania infantum is associated with the impairment of follicular dendritic cells, CXCL13 expression, B cell migration and germinal center formation and associates these changes with severe clinical forms of visceral leishmaniasis. Furthermore the fact that this work uses dogs naturally infected with Leishmania infantum emphasizes the relevance of the data presented herein for the knowledge on the canine and human visceral leishmaniasis.

  17. Immunodominant antigens of Leishmania chagasi associated with protection against human visceral leishmaniasis.

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    Daniel R Abánades

    Full Text Available BACKGROUND: Protection and recovery from visceral leishmaniasis (VL have been associated with cell-mediated immune (CMI responses, whereas no protective role has been attributed to humoral responses against specific parasitic antigens. In this report, we compared carefully selected groups of individuals with distinct responses to Leishmania chagasi to explore antigen-recognizing IgG present in resistant individuals. METHODOLOGY AND PRINCIPAL FINDINGS: VL patients with negative delayed-type hypersensitivity (DTH were classified into the susceptible group. Individuals who had recovered from VL and converted to a DTH+ response, as well as asymptomatic infected individuals (DTH+, were categorized into the resistant group. Sera from these groups were used to detect antigens from L. chagasi by conventional and 2D Western blot assays. Despite an overall reduction in the reactivity of several proteins after DTH conversion, a specific group of proteins (approximately 110-130 kDa consistently reacted with sera from DTH converters. Other antigens that specifically reacted with sera from DTH+ individuals were isolated and tandem mass spectrometry followed by database query with the protein search engine MASCO were used to identify antigens. The serological properties of recombinant version of the selected antigens were tested by ELISA. Sera from asymptomatic infected people (DTH+ reacted more strongly with a mixture of selected recombinant antigens than with total soluble Leishmania antigen (SLA, with less cross-reactivity against Chagas disease patients' sera. SIGNIFICANCE: Our results are the first evidence of leishmania proteins that are specifically recognized by sera from individuals who are putatively resistant to VL. In addition, these data highlight the possibility of using specific proteins in serological tests for the identification of asymptomatic infected individuals.

  18. A Global Comparative Evaluation of Commercial Immunochromatographic Rapid Diagnostic Tests for Visceral Leishmaniasis

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    Cunningham, Jane; Hasker, Epco; Das, Pradeep; El Safi, Sayda; Goto, Hiro; Mondal, Dinesh; Mbuchi, Margaret; Mukhtar, Maowia; Rabello, Ana; Rijal, Suman; Sundar, Shyam; Wasunna, Monique; Adams, Emily; Menten, Joris; Peeling, Rosanna; Boelaert, Marleen

    2012-01-01

    Background. Poor access to diagnosis stymies control of visceral leishmaniasis (VL). Antibody-detecting rapid diagnostic tests (RDTs) can be performed in peripheral health settings. However, there are many brands available and published reports of variable accuracy. Methods. Commercial VL RDTs containing bound rK39 or rKE16 antigen were evaluated using archived human sera from confirmed VL cases (n = 750) and endemic non-VL controls (n = 754) in the Indian subcontinent (ISC), Brazil, and East Africa to assess sensitivity and specificity with 95% confidence intervals. A subset of RDTs were also evaluated after 60 days’ heat incubation (37°C, 45°C). Interlot and interobserver variability was assessed. Results. All test brands performed well against ISC panels (sensitivity range, 92.8%–100%; specificity range, 96%–100%); however, sensitivity was lower against Brazil and East African panels (61.5%–91% and 36.8%–87.2%, respectively). Specificity was consistently > 95% in Brazil and ranged between 90.8% and 98% in East Africa. Performance of some products was adversely affected by high temperatures. Agreement between lots and readers was good to excellent (κ > 0.73–0.99). Conclusions. Diagnostic accuracy of VL RDTs varies between the major endemic regions. Many tests performed well and showed good heat stability in the ISC; however, reduced sensitivity against Brazilian and East African panels suggests that in these regions, used alone, several RDTs are inadequate for excluding a VL diagnosis. More research is needed to assess ease of use and to compare performance using whole blood instead of serum and in patients coinfected with human immunodeficiency virus. PMID:22942208

  19. [Epidemiological, clinical and biological features of infantile visceral leishmaniasis at Kairouan hospital (Tunisia): about 240 cases].

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    Aissi, W; Ben Hellel, K; Habboul, Z; Ben Sghaier, I; Harrat, Z; Bouratbine, A; Aoun, K

    2015-10-01

    Visceral leishmaniasis (VL) is an important health problem in Tunisia. It is most common in children under five years of age. The governorate of Kairouan (central Tunisia) is one of the most affected foci. The aim of this study was to update the epidemiological, clinical and biological features of the disease. The study concerned all VL cases admitted in the pediatric department of Kairouan hospital during 10 years (from 2004 to 2013). For every patient included in this study and when available, data such as sex, age, geographical origin and the condition of the patient at admission (clinical and biological findings) were collected. The myelogram results were also exploited as well as results of serology, culture, Real-Time polymerase chain reaction (PCR) and isoenzymatic typing of Leishmania isolates. Two hundred and forty cases were recorded. Rural cases (87.1%) were more prevalent than urban ones (12.9%). Age ranged from 2 months to 13 years (median, 18 months). The female/male sex ratio was 1.03. The diagnosis delays ranged from 1 day to 8 months (median, 15 days). The most common clinical symptoms at admission were splenomegaly (97.9%), fever (79.9%) and hepatomegaly (47.3%). The principal biological disturbances were anemia (91.7%), thrombocytopenia (83.9%) and leucopenia (56.1%). Among the different biological tools used for diagnosis confirmation, PCR was the most sensitive (100%). All 43 typed stocks corresponded to Leishmania (L.) infantum species. Although zymodeme MON-1 was predictably the most frequent (27 cases), L. infantum MON-24 and MON-80 were responsible of no negligible numbers of cases (11 and 5 cases respectively). The present study gave an updated epidemiological, clinical and biological profile of infantile VL in Tunisia. The diagnosis delays were considerably shortened compared to previous reports. However, an even earlier diagnosis of cases is needed to improve the disease prognosis. Real-Time PCR showed to be helpful in VL management.

  20. Relative risk of visceral leishmaniasis in Brazil: a spatial analysis in urban area.

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    Valdelaine Etelvina Miranda de Araújo

    2013-11-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a vector-borne disease whose factors involved in transmission are poorly understood, especially in more urban and densely populated counties. In Brazil, the VL urbanization is a challenge for the control program. The goals were to identify the greater risk areas for human VL and the risk factors involved in transmission. METHODOLOGY: This is an ecological study on the relative risk of human VL. Spatial units of analysis were the coverage areas of the Basic Health Units (146 small-areas of Belo Horizonte, Minas Gerais State, Brazil. Human VL cases, from 2007 to 2009 (n = 412, were obtained in the Brazilian Reportable Disease Information System. Bayesian approach was used to model the relative risk of VL including potential risk factors involved in transmission (canine infection, socioeconomic and environmental features and to identify the small-areas of greater risk to human VL. PRINCIPAL FINDINGS: The relative risk of VL was shown to be correlated with income, education, and the number of infected dogs per inhabitants. The estimates of relative risk of VL were higher than 1.0 in 54% of the areas (79/146. The spatial modeling highlighted 14 areas with the highest relative risk of VL and 12 of them are concentrated in the northern region of the city. CONCLUSIONS: The spatial analysis used in this study is useful for the identification of small-areas according to risk of human VL and presents operational applicability in control and surveillance program in an urban environment with an unequal spatial distribution of the disease. Thus the frequent monitoring of relative risk of human VL in small-areas is important to direct and prioritize the actions of the control program in urban environment, especially in big cities.

  1. Emerging role of vesicular carriers for therapy of visceral leishmaniasis: conventional versus novel.

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    Kumar, Navneet; Gupta, Swati; Dube, Anuradha; Vyas, Suresh P

    2010-01-01

    Visceral leishmaniasis (VL) is a systemic protozoan infection that infects a million people living in subtropical and tropical areas. Drugs are the major treatment available against this fatal infection. Conventional chemotherapy of VL involves treatment with pen- tavalent antimonials, pentamidine, paromomycin, miltefosine, etc., but this treatment is challenging because of the failure of drugs to penetrate macrophages where the parasite hides, toxic side effects, and drug resistance due to incomplete treatment schedules. The newer therapeutic approach of combination therapy employing multi-drug combinations provides improved treatment of VL because the combination reduces length of treatment, relapse, and risk of toxicity and increases the therapeutic index. Although considerable success has been attained using combination therapies, none has yet achieved commercial status. Therefore, there is an urgent need of designing novel, site-specific leishmanicidal drug carriers for safe and effective management of VL. Colloidal carriers such as liposomes, niosomes, emulsomes, and their engineered versions offer superior therapeutic efficacy over the conventional treatment in terms of site-specific drug delivery related to absolute treatment of disease with reduced side effects and toxicity. The control over spatial and sequential distribution of drug molecules after systemic or localized administration represents the major dispute in drug-delivery systems, and this can be resolved by the use of these colloidal carriers. The present review describes current conventional and combination drug therapies with special consideration given to the emerging role of novel vesicular colloidal carriers designed against VL. Colloidal carriers employing drugs in combination could lead to reductions in the duration of conventional treatment, better patient compliance, and the prevention of anti-leishmanial drug resistance or toxicity.

  2. The household costs of visceral leishmaniasis care in south-eastern Nepal.

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    Surendra Uranw

    Full Text Available BACKGROUND AND OBJECTIVES: Visceral leishmaniasis (VL is an important public health problem in south-eastern Nepal affecting very poor rural communities. Since 2005, Nepal is involved in a regional initiative to eliminate VL. This study assessed the economic impact of VL on households and examined whether the intensified VL control efforts induced by the government resulted in a decrease in household costs. METHODS: Between August and September 2010, a household survey was conducted among 168 patients that had been treated for VL within 12 months prior to the survey in five districts in south-eastern Nepal. We collected data on health-seeking behaviour, direct and indirect costs and coping strategies. RESULTS: The median total cost of one episode of VL was US$ 165 or 11% of annual household income. The median delay between the onset of symptoms and presentation to a qualified provider was 25 days. Once the patient presented to a qualified provider, the delay to correct diagnosis was minimal (median 3 days. Direct and indirect costs (income losses represented 47% and 53% of total costs respectively. Households used multiple strategies to cope with the cost of illness, mainly mobilizing cash/savings (71% or taking a loan (56%. CONCLUSIONS: The provision of free VL diagnosis and drugs by the Nepalese control programme has been an important policy measure to reduce the cost of VL to households. But despite the free VL drugs, the economic burden is still important for households. More effort should be put into reducing indirect costs, in particular the length of treatment, and preventing the transmission of VL through vector control.

  3. Scoring clinical signs can help diagnose canine visceral leishmaniasis in a highly endemic area in Brazil

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    da Silva, Kleverton Ribeiro; de Mendonça, Vitor Rosa Ramos; Silva, Kellen Matuzzy; do Nascimento, Leopoldo Fabrício Marçal; Mendes-Sousa, Antonio Ferreira; de Pinho, Flaviane Alves; Barral-Netto, Manoel; Barral, Aldina Maria Prado; Cruz, Maria do Socorro Pires e

    2017-01-01

    Canine visceral leishmaniasis (CVL) diagnosis is still a challenge in endemic areas with limited diagnostic resources. This study proposes a score with the potential to distinguish positive CVL cases from negative ones. We studied 265 dogs that tested positive for CVL on ELISA and parasitological tests. A score ranging between 0 and 19 was recorded on the basis of clinical signs. Dogs with CVL had an overall higher positivity of the majority of clinical signs than did dogs without CVL or with ehrlichiosis. Clinical signs such as enlarged lymph nodes (83.93%), muzzle/ear lesions (55.36%), nutritional status (51.79%), bristle condition (57.14%), pale mucosal colour (48.21%), onychogryphosis (58.93%), skin lesion (39.28%), bleeding (12.50%), muzzle depigmentation (41.07%), alopecia (39.29%), blepharitis (21.43%), and keratoconjunctivitis (42.86%) were more frequent in dogs with CVL than in dogs with ehrlichiosis or without CVL. Moreover, the clinical score increased according to the positivity of all diagnostic tests (ELISA, p < 0.001; parasite culture, p = 0.0021; and smear, p = 0.0003). Onychogryphosis (long nails) [odds ratio (OR): 3.529; 95% confidence interval (CI): 1.832-6.796; p < 0.001], muzzle depigmentation (OR: 4.651; 95% CI: 2.218-9.750; p < 0.001), and keratoconjunctivitis (OR: 5.400; 95% CI: 2.549-11.441; p < 0.001) were highly associated with CVL. Interestingly, a score cut-off value ≥ 6 had an area under the curve of 0.717 (p < 0.0001), sensitivity of 60.71%, and specificity of 73.64% for CVL diagnosis. The clinical sign-based score for CVL diagnosis suggested herein can help veterinarians reliably identify dogs with CVL in endemic areas with limited diagnostic resources. PMID:28076469

  4. Visceral leishmaniasis epidemiologic evolution in timeframes, based on demographic changes and scientific achievements in Brazil.

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    Conti, Renata Vivas; Moura Lane, Viviane Fragoso; Montebello, Lucia; Pinto Junior, Vitor Laerte

    2016-01-01

    Visceral leishmaniasis (VL) is a disease of chronic evolution which could be uniformly fatal, if left untreated. Human VL was first described in the Americas in 1913 and in 1936 in Brazil. The number of VL cases in Brazil is increasing steadily in the last three decades. Medical literature highlights this change in the disease epidemiology as a recent urbanization phenomenon, with most of the cases occurring in large cities since 1981, different to that observed previously, like a typical rural endemic. The aim of this study was to create a narrative review of the evolution of VL epidemiology since its first description in Brazil. To describe the process of urbanization of VL, timeframes were created historically consistent with the scientific and public health knowledge obtained about the VL and the demographics changes in Brazil, especially considering the extensive migratory movements in the country due to political or economic events. The first phase of VL was the decades of 30-50 when industrialization triggered internal migration process from countryside to the cities; during this period VL was studied for the first time and described as a rural endemic disease with no relevance to public health. Until the second phase, between the 50s and 80s of the 20th century, demography was characterized by expansion of immigration to the large cities and increase in population density in the suburbs with poor living standards. In this period, there was an advancement in the knowledge of the transmission of the disease being described as the first case acquired in the urban environment. The third phase was characterized by the explosion of cases in Brazilian cities and consolidation of urban endemic transmission. The possibility of urban transmission has been known since the 50s; however, the current phenomenon was due to the creation of ideal conditions for the establishment of transmission cycle in Brazilian cities.

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

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    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.

  6. Prognostic factors and scoring system for death from visceral leishmaniasis: an historical cohort study in Brazil.

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    Wendel Coura-Vital

    2014-12-01

    Full Text Available In Brazil, case-fatality rates attributable to visceral leishmaniasis (VL are high and knowledge of the risk factors associated with death may help reduce mortality. The aim of this study was to construct and validate a scoring system for prognosis of death from VL by using all cases reported in Brazil from 2007 to 2011.In this historical cohort study, 18,501 VL cases were analyzed; of these, 17,345 cases were cured and 1,156 cases caused death. The database was divided into two series: primary (two-thirds of cases, to develop the model score, and secondary (one-third of cases, to validate the scoring system. Multivariate logistic regression models were performed to identify factors associated with death from VL, and these were included in the scoring system.The factors associated with death from VL were: bleeding (score 3; splenomegaly (score 1; edema (score 1; weakness (score 1; jaundice (score 1; Leishmania-HIV co-infection (score 1; bacterial infection (score 1; and age (≤0.5 years [score 5]; >0.5 and ≤1 [score 2]; >19 and ≤50 [score 2]; >50 and <65 [score 3]; ≥65 [score 5]. It was observed that patients with a score of 4 had a probability of death of approximately 4.5% and had a worse prognosis. The sensitivity, specificity, and accuracy of this score were 89.4, 51.2, and 53.5, respectively.The scoring system based on risk factors for death showed good performance in identifying patients with signs of severity at the time of clinical suspicion of VL and can contribute to improving the surveillance system for reducing case fatalities. The classification of patients according to their prognosis for death may assist decision-making regarding the transfer of the patients to hospitals more capable of handling their condition, admission to the intensive care unit, and adequate support and specific treatment.

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

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    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.

  8. Leishmania donovani triose phosphate isomerase: a potential vaccine target against visceral leishmaniasis.

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    Pramod K Kushawaha

    Full Text Available Visceral leishmaniasis (VL is one of the most important parasitic diseases with approximately 350 million people at risk. Due to the non availability of an ideal drug, development of a safe, effective, and affordable vaccine could be a solution for control and prevention of this disease. In this study, a potential Th1 stimulatory protein- Triose phosphate isomerase (TPI, a glycolytic enzyme, identified through proteomics from a fraction of Leishmania donovani soluble antigen ranging from 89.9-97.1 kDa, was assessed for its potential as a suitable vaccine candidate. The protein- L. donovani TPI (LdTPI was cloned, expressed and purified which exhibited the homology of 99% with L. infantum TPI. The rLdTPI was further evaluated for its immunogenicity by lymphoproliferative response (LTT, nitric oxide (NO production and estimation of cytokines in cured Leishmania patients/hamster. It elicited strong LTT response in cured patients as well as NO production in cured hamsters and stimulated remarkable Th1-type cellular responses including IFN-ã and IL-12 with extremely lower level of IL-10 in Leishmania-infected cured/exposed patients PBMCs in vitro. Vaccination with LdTPI-DNA construct protected naive golden hamsters from virulent L. donovani challenge unambiguously (∼90%. The vaccinated hamsters demonstrated a surge in IFN-ã, TNF-á and IL-12 levels but extreme down-regulation of IL-10 and IL-4 along with profound delayed type hypersensitivity and increased levels of Leishmania-specific IgG2 antibody. Thus, the results are suggestive of the protein having the potential of a strong candidate vaccine.

  9. Diagnosis of human African trypanosomiasis and visceral leishmaniasis based on the detection of anti-parasite-enzyme antibodies.

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    Borowy, N K; Schell, D; Schäfer, C; Overath, P

    1991-08-01

    A sensitive diagnostic assay for parasitic infections based on the detection of anti-enzyme antibodies is presented. All serum antibodies produced in response to parasite antigens are immobilized via their Fc domain on matrix-bound protein G. Incubation of the immobilized antibodies with saturating amounts of parasite extract results in the binding of all recognized antigens, including those directed against a specific and readily measurable enzyme. The amount of bound enzyme is proportional to the anti-enzyme antibody concentration in the serum. The application of this principle is demonstrated for the diagnosis of both human African trypanosomiasis and visceral leishmaniasis by the detection of antibodies against parasite acid phosphatases.

  10. A Comparison of Liposomal Amphotericin B with Sodium Stibogluconate for the Treatment of Visceral Leishmaniasis in Pregnancy in Sudan.

    OpenAIRE

    Mueller, M; Balasegaram, M.; Koummuki, Y; Ritmeijer, K.; Santana, M R; Davidson, R N N

    2006-01-01

    OBJECTIVES: Little is known about the treatment of visceral leishmaniasis (VL) in pregnancy, especially in resource-poor settings. We present a series of pregnant women with VL treated with either sodium stibogluconate or liposomal amphotericin B (AmBisome), or both, in eastern Sudan over 16 months. METHODS: We did a retrospective analysis of all pregnant VL patients treated in the Médecins sans Frontières (MSF) Um el Kher centre between January 2004 and April 2005. We diagnosed VL with labor...

  11. Heterogeneity of Leishmania donovani parasites complicates diagnosis of visceral leishmaniasis: comparison of different serological tests in three endemic regions.

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    Elfadil Abass

    Full Text Available Diagnostic tests for visceral leishmaniasis that are based on antigens of a single Leishmania strain can have low diagnostic performance in regions where heterologous parasites predominate. The aim of this study was to investigate and compare the performance of five serological tests, based on different Leishmania antigens, in three endemic countries for visceral leishmaniasis. A total number of 231 sera of symptomatic and asymptomatic cases and controls from three endemic regions of visceral leishmaniasis in East Sudan, North India and South France were evaluated by following serological tests: rKLO8- and rK39 ELISA, DAT (ITMA-DAT and two rapid tests of rK39 (IT LEISH and rKE16 (Signal-KA. Overall, rKLO8- and rK39 ELISA were most sensitive in immunocompetent patients from all endemic regions (96-100% and the sensitivity was reduced to 81.8% in HIV co-infected patients from France. Sera of patients from India demonstrated significantly higher antibody responses to rKLO8 and rK39 compared with sera from Sudan (p<0.0001 and France (p<0.0037. Further, some Indian and Sudanese patients reacted better with rKLO8 than rK39. Sensitivity of DAT (ITMA-DAT was high in Sudan (94% and India (92.3% but low in France being 88.5% and 54.5% for VL and VL/HIV patients, respectively. In contrast, rapid tests displayed high sensitivity only in patients from India (96.2% but not Sudan (64-88% and France (73.1-88.5% and 63.6-81.8% in VL and VL/HIV patients, respectively. While the sensitivity varied, all tests showed high specificity in Sudan (96.7-100% and India (96.6%.Heterogeneity of Leishmania parasites which is common in many endemic regions complicates the diagnosis of visceral leishmaniasis. Therefore, tests based on homologous Leishmania antigens are required for particular endemic regions to detect cases which are difficult to be diagnosed with currently available tests.

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

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    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.

  13. Serological markers of sand fly exposure to evaluate insecticidal nets against visceral leishmaniasis in India and Nepal: a cluster-randomi trial

    DEFF Research Database (Denmark)

    Gidwani, K; Picado, A; Rijal, S

    2011-01-01

    Background: Visceral leishmaniasis is the world’ second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness...... against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial. Methods: As part of a paired-cluster randomized controlled clinical trial in VL-endemic regions of India...

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

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    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

  15. Cationic solid-lipid nanoparticles are as efficient as electroporation in DNA vaccination against visceral leishmaniasis in mice.

    Science.gov (United States)

    Saljoughian, N; Zahedifard, F; Doroud, D; Doustdari, F; Vasei, M; Papadopoulou, B; Rafati, S

    2013-12-01

    The use of an appropriate delivery system has recently emerged as a promising approach for the development of effective vaccination against visceral leishmaniasis (VL). Here, we compare two vaccine delivery systems, namely electroporation and cationic solid-lipid nanoparticle (cSLN) formulation, to administer a DNA vaccine harbouring the L. donovani A2 antigen along with L. infantum cysteine proteinases [CPA and CPB without its unusual C-terminal extension (CPB(-CTE) )] and evaluate their potential against L. infantum challenge. Prime-boost administration of the pcDNA-A2-CPA-CPB(-CTE) delivered by either electroporation or cSLN formulation protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-γ and lower levels of IL-10 production, leading to a strong Th1 immune response. At all time points, the ratio of IFN-γ: IL-10 induced upon restimulation with rA2-rCPA-rCPB and F/T antigens was significantly higher in vaccinated animals. Moreover, Th2-efficient protection was elicited through a high humoral immune response. Nitric oxide production, parasite burden and histopathological analysis were also in concordance with other findings. Overall, these data indicate that similar to the electroporation delivery system, cSLNs as a nanoscale vehicle of Leishmania antigens could improve immune response, hence indicating the promise of these strategies against visceral leishmaniasis.

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

    Science.gov (United States)

    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

  17. Evaluation of a pamphlet on visceral leishmaniasis as a tool for providing disease information to healthcare professionals and laypersons.

    Science.gov (United States)

    Luz, Zélia Maria Profeta da; Schall, Virgínia; Rabello, Ana

    2005-01-01

    Although educational materials are frequently produced and used as part of control programs in Brazil, little is known about the efficacy of this type of information. This study evaluated the potential for disseminating information on visceral leishmaniasis using a pamphlet. The sample consisted of 551 healthcare workers and 379 laypeople from a metropolitan area located in southeast Brazil. Both before and after reading the pamphlet, subjects completed a multiple-choice questionnaire. Overall baseline knowledge of the disease was estimated by the proportion of correct answers before reading the pamphlet. Although specific knowledge among zoonosis control workers was higher (90.0% on average), overall baseline knowledge of the disease varied from 45.0% to 77.0%. After reading the pamphlet, the levels increased to 71.0% and 96.0%, respectively. Before reading, the lowest proportion of correct answers in all groups related to the disease symptoms. Analysis of incorrect answers showed that visceral leishmaniasis is mainly confused with leptospirosis. The increased proportion of correct answers after reading the pamphlet is evidence of its potential as an educational tool.

  18. Lutzomyia longipalpis spatial distribution and association with environmental variables in an urban focus of visceral leishmaniasis, Misiones, Argentina.

    Science.gov (United States)

    Fernández, María Soledad; Salomón, Oscar Daniel; Cavia, Regino; Perez, Adriana Alicia; Acardi, Soraya A; Guccione, José Daniel

    2010-05-01

    This study describes the spatial distribution pattern of Lu. longipalpis abundance in Posadas-Garupá, Argentina, where four cases of human Visceral Leishmaniasis had been recorded. A total of 2428 Lu. longipalpis were captured in 42% of the 305 sites sampled with CDC light traps, its abundance shows spatial autocorrelation ranging up to 590 m (semivariogram model), with six downtown 'islands' of vector highest abundance (>or=60 individuals). A significant association between Lu. longipalpis and the presence of chickens was observed (odds ratio 3.26). The best stepwise multiple regression using Generalized Linear Models explained 31% of the deviance for Lu. longipalpis abundance, including as explanatory variables: (a) negatively: households with 'lack of building material and with economic deprivation', (b) positively: surface covered by trees and bushes at 50 meters of the house, and households without electrical lighting. In conclusion, Lu. longipalpis in a recent settled focus of visceral leishmaniasis was urbanized with a highly heterogeneous spatial distribution within the cities, with the vectors concentrated in limited 'islands' of high abundance, in the downtown relatively more affluent and dense populated areas, but also more heterogeneous with patches that had higher tree coverage and poor urban services. These results once validated will contribute to the control strategy design through risk maps, in order to prioritize areas for prevention and control, and setting the appropriate scale for intervention.

  19. Association of pro-inflammatory cytokines and iron regulatory protein 2 (IRP2 with Leishmania burden in canine visceral leishmaniasis.

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    Paulo Ricardo Porfírio do Nascimento

    Full Text Available Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2 were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.

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

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    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.

  1. Thick Smear is a Good Substitute for the Thin Smear in Parasitological Confirmation of Canine Visceral Leishmaniasis.

    Science.gov (United States)

    de Mello, Cintia Xavier; Figueiredo, Fabiano Borges; Mendes Júnior, Artur Augusto Velho; Miranda, Luciana de Freitas Campos; de Oliveira, Raquel de Vasconcellos Carvalhaes; Madeira, Maria de Fátima

    2016-07-01

    Although direct examination methods are important for diagnosing leishmaniasis, such methods are often neglected because of their low sensitivity relative to other techniques. Our study aimed to evaluate the performance of bone marrow (BM) thick smears and cytocentrifugation tests as alternatives to direct examination for diagnosing canine visceral leishmaniasis (CVL). Ninety-two dogs exhibiting leishmaniasis seroreactivity were evaluated. The animals were euthanized; and healthy skin, spleen, popliteal lymph node, and BM puncture samples were cultured. BM cultures were used as the reference standard. Of the 92 dogs studied, 85.9% exhibited positive cultures, and Leishmania infantum (synonym Leishmania chagasi) was confirmed in all positive culture cases. The sensitivity rates for cytocentrifugation as well as thin and thick smears were 47.1%, 52.8%, and 77%, respectively. However, no association between the dogs' clinical status and culture or direct examination results was found. To our knowledge, this was the first study to use thick smears and cytocentrifugation for diagnosing CVL. Our results indicate that BM thick smears have a good sensitivity and their use reduces the time required to read slides. Therefore, thick smears can provide a rapid and safe alternative to parasitological confirmation of seroreactive dogs.

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

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    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.

  3. IL10 Variant g.5311A Is Associated with Visceral Leishmaniasis in Indian Population.

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    Anshuman Mishra

    Full Text Available Visceral leishmaniasis (VL is a multifactorial disease, where the host genetics play a significant role in determining the disease outcome. The immunological role of anti-inflammatory cytokine, Interleukin 10 (IL10, has been well-documented in parasite infections and considered as a key regulatory cytokine for VL. Although VL patients in India display high level of IL10 in blood serum, no genetic study has been conducted to assess the VL susceptibility / resistance. Therefore, the aim of this study is to investigate the role of IL10 variations in Indian VL; and to estimate the distribution of disease associated allele in diverse Indian populations.All the exons and exon-intron boundaries of IL10 were sequenced in 184 VL patients along with 172 ethnically matched controls from VL endemic region of India.Our analysis revealed four variations; rs1518111 (2195 A>G, intron, rs1554286 (2607 C>T, intron, rs3024496 (4976 T>C, 3' UTR and rs3024498 (5311 A>G, 3' UTR. Of these, a variant g.5311A is significantly associated with VL (χ2=18.87; p =0.00001. In silico approaches have shown that a putative micro RNA binding site (miR-4321 is lost in rs3024498 mRNA. Further, analysis of the above four variations in 1138 individuals from 34 ethnic populations, representing different social and linguistic groups who are inhabited in different geographical regions of India, showed variable frequency. Interestingly, we have found, majority of the tribal populations have low frequency of VL ('A' of rs3024498; and high frequency of leprosy ('T' of rs1554286, and Behcet's ('A' of rs1518111 associated alleles, whereas these were vice versa in castes. Our findings suggest that majority of tribal populations of India carry the protected / less severe allele against VL, while risk / more severe allele for leprosy and Behcet's disease. This study has potential implications in counseling and management of VL and other infectious diseases.

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

    Science.gov (United States)

    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

  5. Risk analysis and prediction of visceral leishmaniasis dispersion in São Paulo State, Brazil

    Science.gov (United States)

    Mao, Liang; Galvis-Ovallos, Fredy; Tucker Lima, Joanna Marie; Valle, Denis

    2017-01-01

    Visceral leishmaniasis (VL) is an important neglected disease caused by a protozoan parasite, and represents a serious public health problem in many parts of the world. It is zoonotic in Europe and Latin America, where infected dogs constitute the main domestic reservoir for the parasite and play a key role in VL transmission to humans. In Brazil this disease is caused by the protozoan Leishmania infantum chagasi, and is transmitted by the sand fly Lutzomyia longipalpis. Despite programs aimed at eliminating infection sources, the disease continues to spread throughout the Country. VL in São Paulo State, Brazil, first appeared in the northwestern region, spreading in a southeasterly direction over time. We integrate data on the VL vector, infected dogs and infected human dispersion from 1999 to 2013 through an innovative spatial temporal Bayesian model in conjunction with geographic information system. This model is used to infer the drivers of the invasion process and predict the future progression of VL through the State. We found that vector dispersion was influenced by vector presence in nearby municipalities at the previous time step, proximity to the Bolívia-Brazil gas pipeline, and high temperatures (i.e., annual average between 20 and 23°C). Key factors affecting infected dog dispersion included proximity to the Marechal Rondon Highway, high temperatures, and presence of the competent vector within the same municipality. Finally, vector presence, presence of infected dogs, and rainfall (approx. 270 to 540mm/year) drove the dispersion of human VL cases. Surprisingly, economic factors exhibited no noticeable influence on disease dispersion. Based on these drivers and stochastic simulations, we identified which municipalities are most likely to be invaded by vectors and infected hosts in the future. Prioritizing prevention and control strategies within the identified municipalities may help halt the spread of VL while reducing monitoring costs. Our results

  6. [Evaluation of clinical and laboratory findings of adult visceral leishmaniasis cases].

    Science.gov (United States)

    Ural, Serap; Kaptan, Figen; Sezak, Nurbanu; El, Sibel; Örmen, Bahar; Türker, Nesrin; Demirdal, Tuna; Vardar, İlknur; Özkan Çayıröz, Pınar; Çakalağaoğlu, Fulya

    2015-10-01

    Visceral leishmaniasis (VL, kala-azar) is a zoonotic infection caused by Leishmania species which are transmitted to humans by the bites of infected female phlebotomine sandflies. Leishmania infantum is the responsible species of VL in Aegean, Mediterranean, and Central Anatolia regions of Turkey mainly observed sporadically in pediatric age groups. The aim of this study was to evaluate the clinical and laboratory findings of adult patients with VL who were admitted to our hospital. A total of 10 patients (3 female, 7 male; age range: 18-67 years, mean age: 39.3 ± 16.51) followed in the infectious diseases clinic of the hospital between 2000 and 2013 were evaluated retrospectively. The diagnosis of VL was based on the presence of appropriate clinical and physical examination, as well as biochemical findings, positive serological test results (indirect fluorescent antibody test, and rK39 rapid antigen test) and/or detection of amastigote forms of parasite in the bone marrow aspiration samples. Of the cases three were diagnosed with both bone marrow and serology positivity, five with bone marrow positivity and one of each only with liver biopsy and positive serology result. Time interval from onset of the symptoms until the establishment of the specific clinical diagnosis was ranged from 2 to 12 weeks. The most frequent initial symptoms were fever, fatigue and abdominal distension. None of the patients had immunosupressive conditions such as HIV infection, corticosteroid use, immunosupressive treatment, or transplantation. All the patients were from Aegean region and six were living in rural areas. In all cases, hepatosplenomegaly, increased erythrocyte sedimentation rate, albumin/globulin ratio inversion, anemia, leukopenia and among nine cases trombocytopenia were detected. In one case acute renal failure has been developed before treatment and the patient was admitted to dialysis program. Bacterial superinfection occurred in two cases. Patients were treated with

  7. 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.

    Science.gov (United States)

    Michalsky, Erika Monteiro; Fortes-Dias, Consuelo Latorre; França-Silva, João Carlos; Rocha, Marilia Fonseca; Barata, Ricardo Andrade; Dias, Edelberto Santos

    2009-12-01

    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.

  8. 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

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    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.

  9. Cysteine proteinase type III is protective against Leishmania infantum infection in BALB/c mice and highly antigenic in visceral leishmaniasis individuals.

    Science.gov (United States)

    Khoshgoo, Naghmeh; Zahedifard, Farnaz; Azizi, Hiva; Taslimi, Yasaman; Alonso, Maribel Jiménez; Rafati, Sima

    2008-10-29

    Visceral leishmaniasis is the most acute form of leishmaniasis and vaccination is the best approach to control it. One of the major groups of virulence factors in Leishmania belongs to cysteine proteinase family. In this study, for the first time, the protective potential of Leishmania infantum cysteine proteinase type III (CPC) by using a prime-boost strategy is evaluated in BALB/c mice. The experiment was carried out in three groups of mice. Vaccinated group was primed with pcDNA-cpc and boosted with rCPC-DHFR in combination with CpG motif and Montanide 720 as adjuvant. Control groups received pcDNA and rDHFR or PBS. The ratio of IgG2a/IgG1, nitric oxide concentration and IFN-gamma induction in vaccinated group is significantly higher than controls. Furthermore, the parasite load of vaccinated group is significantly lower than controls. In addition, sera reactivity of visceral leishmaniasis individuals was examined and showed considerable reactivities toward rCPC in comparison with cutaneous leishmaniasis. The achieved result is highly encouraging the use of cysteine proteinases types I, II and III as vaccine candidate against visceral leishmaniasis.

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

    Science.gov (United States)

    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....

  11. Leishmaniose visceral adquirida no Estado de São Paulo (Brasil A case of visceral leishmaniasis contracted in the State of S. Paulo, Brazil

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    Vicente Amato Neto

    1981-12-01

    Full Text Available Foi descrita a notificação de um caso de leishmaniose visceral em uma criança com dois anos de idade, tendo sempre residido em Capão Redondo, localidade situada na Grande São Paulo (Brasil. Apesar de transmissão congênita ou por transfusão de sangue ter sido cogitada, é provável que a infecção tenha decorrido de mecanismo habitual, consubstanciando ocorrência autóctone relativa do Estado de São Paulo.A case of visceral leishmaniasis in a two-year-old child who has always lived in Capão Redondo, situated in Greater S. Paulo (Brazil, was reported. Although congenital transmission or blood transfusion were considered, it is probable that the infection originated in the usual mechanism, thus constituting an autochthonous occurrence in the State of S. Paulo. The State Health Department was notified of the case in order that it could be investigated and necessary measures taken.

  12. Relationship between rainfall and temperature: observations on the cases of visceral leishmaniasis in São Luis Island, State of Maranhão, Brazil

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    Graça Maria de Castro Viana

    2011-12-01

    Full Text Available INTRODUCTION: Visceral leishmaniasis is a serious public health problem that requires global control strategies, especially with respect to factors that may intervene in reducing the incidence of endemicity. In this work, rainfall density and temperature were correlated with the incidence of human cases in an area endemic for leishmaniasis in São Luis do Maranhão, Northeastern Brazil. METHODS: Notification of human cases by the National Health Foundation/Regional Coordination of Maranhão (FUNASA/COREMA from 2002 to 2010 was used. Ecological data (mean temperature and rainfall density were provided by the Meteorological Office of State. RESULTS: A significant association was verified between the number of VL cases and rainfall rate but not in the analysis concerning mean temperatures. CONCLUSIONS: These data suggest that the control actions in visceral leishmaniasis should be performed during rainy season in the State of Maranhão, which is in the first half of the year.

  13. Estudio del perfil electroforético en sueros de caninos con leishmaniasis visceral de Posadas, provincia de Misiones, Argentina Study of the sera electrophoretic profile in dogs infected with visceral leishmaniasis from Posadas, Misiones, Argentina

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    L.G. Ramayo

    2011-12-01

    Full Text Available La leishmaniasis visceral es una enfermedad zoonótica producida por el protozoario Leishmania infantum (syn. chagasi transmitida por el flebótomo Lutzomyia longipalpis y que tiene al canino como principal reservorio en áreas urbanas y periurbanas. En el presente trabajo se realizó un estudio electroforético retrospectivo de 40 sueros de caninos enfermos con diagnóstico parasitológico confirmado de leishmaniasis obtenidos entre los años 2006 y 2008 en la ciudad de Posadas, provincia de Misiones, Argentina. El 80 % (32 de 40 de las muestras presentaron alteraciones en el perfil electroforético caracterizadas por la disminución de la relación albúmina/globulina y la presencia de hipergammaglobulinemia de tipo policlonal en el 52,5 % de los casos (21 de 40 y de hipergammaglobulinemia de tipo monoclonal a isotipo IgG en el 27,5 % (11 de 40 de ellos. Cinco de los sueros con anormalidades en el perfil electroforético mostraron valores normales de proteinemia; el resto presentó hiperproteinemia. Estos resultados muestran que la hipergammaglobulinemia y la disminución de la relación albúmina/globulina fueron hallazgos clínico patológicos frecuentes en este brote, tal como se describe en otras partes del mundo.Visceral leishmaniasis in a zoonotic disease caused by protozoan Leishmania infantum (syn. chagasi, transmited by phlebotomine Lutzomyia longipalpis. Canines are its main reservoir in urban and suburban areas. Forty sera from sick dogs with leishmaniasis confirmed by parasitological diagnosis were analized in a retrospective study. Sera were obtained during 2006-2008 in the city of Posadas, Misiones province, Argentina. Eighty % (32 out of 40 of these samples showed distortions in the electrophoretic profile, characterized by a diminished albumin/globulin ratio and the presence of polyclonal hypergammaglobulinemia in 52.5 % (21 out of 40 of the samples, or IgG-monoclonal hypergammaglobulinemia in 27.5 % (11 out of 40 of the

  14. 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.

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    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.

  15. Enhanced efficacy and immunogenicity of 78kDa antigen formulated in various adjuvants against murine visceral leishmaniasis.

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    Nagill, Rajeev; Kaur, Sukhbir

    2010-05-21

    Leishmania infection causes localized cutaneous to severe visceral disease in humans and animals. Current control measures, based on antimonial compounds, are not effective because of resistance in Leishmania. Vaccination would be a feasible alternative, but as yet no vaccine to protect humans against infection has been commercialized. Parasite antigens that preferentially stimulate the induction of significant protection through Th1 response presents a rational approach for a vaccine against leishmaniasis. With this view in mind, we investigated the potential of 78kDa antigen of Leishmania donovani alone and along with different adjuvants against murine visceral leishmaniasis. Various adjuvants used along with 78kDa antigen include monophosphoryl lipid A (MPL-A), liposomal encapsulation, recombinant IL-12, autoclaved Leishmania antigen (ALD) and Freund's adjuvant (FCA). BALB/c mice were immunized subcutaneously thrice with respective vaccine formulation. Challenge infection was given intracardially after 2 weeks of second booster. A significant decrease in parasite burden was seen in vaccinees over the infected controls on all post challenge days and was found that maximum protection was provided by 78kDa+rIL-12 vaccine and it was highly immunogenic as depicted by the reduction in parasite load (71-94.8%), reduction in infection rate of peritoneal macrophages (92.9-98%), enhanced DTH response (6.5-10.5 fold), increase in IgG2a anti-leishmanial antibody production (3-3.7 fold) and up-regulation of IFN-gamma (3.7-6.5 fold) and IL-2 levels (7.7-12.3 fold), which demonstrate the generation of protective Th1 type of immune response. Comparable results were also observed in 78kDa+MPL-A and liposome-encapsulated 78kDa vaccines with 56.5-92% and 62.9-93.4% reduction in parasite load respectively. Significant results have also been obtained with 78kDa antigen+ALD, 78kDa antigen+FCA and 78kDa antigen alone group but the protective efficacy was reduced as compared to the

  16. Identification of small molecule lead compounds for visceral leishmaniasis using a novel ex vivo splenic explant model system.

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    Yaneth Osorio

    Full Text Available BACKGROUND: New drugs are needed to treat visceral leishmaniasis (VL because the current therapies are toxic, expensive, and parasite resistance may weaken drug efficacy. We established a novel ex vivo splenic explant culture system from hamsters infected with luciferase-transfected Leishmania donovani to screen chemical compounds for anti-leishmanial activity. METHODOLOGY/PRINCIPAL FINDINGS: THIS MODEL HAS ADVANTAGES OVER IN VITRO SYSTEMS IN THAT IT: 1 includes the whole cellular population involved in the host-parasite interaction; 2 is initiated at a stage of infection when the immunosuppressive mechanisms that lead to progressive VL are evident; 3 involves the intracellular form of Leishmania; 4 supports parasite replication that can be easily quantified by detection of parasite-expressed luciferase; 5 is adaptable to a high-throughput screening format; and 6 can be used to identify compounds that have both direct and indirect anti-parasitic activity. The assay showed excellent discrimination between positive (amphotericin B and negative (vehicle controls with a Z' Factor >0.8. A duplicate screen of 4 chemical libraries containing 4,035 compounds identified 202 hits (5.0% with a Z score of <-1.96 (p<0.05. Eighty-four (2.1% of the hits were classified as lead compounds based on the in vitro therapeutic index (ratio of the compound concentration causing 50% cytotoxicity in the HepG(2 cell line to the concentration that caused 50% reduction in the parasite load. Sixty-nine (82% of the lead compounds were previously unknown to have anti-leishmanial activity. The most frequently identified lead compounds were classified as quinoline-containing compounds (14%, alkaloids (10%, aromatics (11%, terpenes (8%, phenothiazines (7% and furans (5%. CONCLUSIONS/SIGNIFICANCE: The ex vivo splenic explant model provides a powerful approach to identify new compounds active against L. donovani within the pathophysiologic environment of the infected spleen

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

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    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

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

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    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

  19. Host preferences of the sand fly Lutzomyia longipalpis at an endemic focus of American visceral leishmaniasis in Colombia.

    Science.gov (United States)

    Morrison, A C; Ferro, C; Tesh, R B

    1993-07-01

    Blood meals from 579 Lutzomyia longipalpis (Diptera:Psychodidae), collected in an endemic focus of American visceral leishmaniasis in Colombia, were identified by precipitin test. Sand fly collections were made during a 16-month period from the inside walls of two houses, a pigpen, and rock crevices in a small community (El Callejon) within the endemic area. Feeding patterns of the sand flies varied with locality and date of collection. Overall, bovine feedings predominated, but feedings were also recorded on pigs, equines, humans, dogs, opossums, birds, and reptiles. Calculation of the forage ratios for each host species indicated that cows and pigs were the preferred hosts of Lu. longipalpis in El Callejon. Results of this study suggest that Lu. longipalpis is an opportunistic feeder and is not highly anthropophilic nor strongly attracted to dogs.

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

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    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.

  1. Age related efficiency of the leishmanin skin test as a marker of immunity to human visceral leishmaniasis.

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    Sassi, A; Ben Salah, A; Hamida, N Bel Haj; Zaatour, A

    2012-01-01

    This study aimed at investigating whether the efficiency of the leishmanin skin test (LST) to evaluate the immune status of individuals exposed to Leishmania (L.) infantum is age-related. It was conducted in two districts of the governorate of Kairouan, an endemic region for L. infantum infection in Tunisia. Healthy individuals (n = 119) were selected according to two criteria: no current or past history of visceral or cutaneous leishmaniasis, and their age range: 1-6 years (group I), 7-14 years (group II), and 20-66 years old (group III). Assessments comprised LSTs, in vitro lymphoproliferative response, and interferon-gamma (IFN-gamma) productions induced by soluble leishmanial antigens (SLA). LST recorded an overall of 89.07% and 89.9% concordance with T cell proliferation and IFN-gamma production induced by SLA, respectively. Using in vitro tests as gold standards, LST was found more sensitive for screening individuals from group I (96% and 100%, considering T cell proliferation and IFN-gamma production results, respectively), than group II (91% and 97%) and group III (70% and 74%,). Conversely, LST was less specific in group I (84% and 77%) than group II (100% and 94%) and group III (100% for both in vitro tests). Our results suggested that the strength of LST resided in its higher sensitivity, to unravel asymptomatic injections and cell mediated immunity to L. infantum parasite in infants and its higher specificity for screening adult individuals. Negative LST in adults and positive LST in children < 5 years, the population at risk of developing visceral leishmaniasis, remain the weaknesses of LST and should be interpreted with caution.

  2. Awareness of visceral leishmaniasis and its relationship to canine infection in riverside endemic areas in Northeastern Brazil

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    Kalidia Felipe de Lima Costa

    2014-10-01

    Full Text Available Introduction An awareness of visceral leishmaniasis (VL is necessary to encourage the population to participate in prevention and control in collaboration with more efficient, centrally organized health programs. The aim of this study was to evaluate the awareness of the riverside population regarding VL and the association between awareness and the prevalence of canine visceral leishmaniasis (CVL. Methods In total, 71 people living in riverside areas in the City of Mossoró in State of Rio Grande do Norte participated of the study, and 71 dogs were tested for CVL by polymerase chain reaction (PCR. Association analysis of several variables related to knowledge of the riverside population regarding CVL positivity was performed, yielding odds ratios (OR and 95% confidence intervals (CI, and significance was determined using chi-square (χ2 and Fisher's exact tests. Results Among individuals whose dogs tested positive for CVL, 60% did not know the cure for CVL, and these subjects were three times more likely to have a dog test positive for CVL than those who were aware the cure for CVL. Knowledge of CVL cure was the only variable that remained in the logistic model after the successive removal of variables, with an adjusted OR of 3.11 (95%CI: 1.1-8,799; p=0.032. Conclusions Insufficient awareness regarding VL in riverside areas with CVL-positive dogs was associated with increased rates of canine infection, which suggests that changes in habits and the adoption of attitudes and preventive practices may contribute to the control and prevention of this disease. This study reinforces the need to invest in better health education programs regarding VL.

  3. Atypical Presentation of PKDL due to Leishmania infantum in an HIV-Infected Patient with Relapsing Visceral Leishmaniasis

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    Benedetto Maurizio Celesia

    2014-01-01

    Full Text Available We describe the case of an Italian patient with HIV infection who developed an atypical rash resembling post-kala-azar dermal leishmaniasis (PKDL when receiving liposomal Amphotericin B (L-AMB for secondary prophylaxis of visceral leishmaniasis (VL. At the time of PKDL appearance, the patient was virologically suppressed but had failed to restore an adequate CD4+ T-cell count. Histology of skin lesions revealed the presence of a granulomatous infiltrate, with lymphocytes, plasma cells, and macrophages, most of which contained Leishmania amastigotes. Restriction fragment length polymorphism-polymerase chain reaction was positive for Leishmania infantum. Paradoxically, cutaneous lesions markedly improved when a new relapse of VL occurred. The patient received meglumine antimoniate, with a rapid clinical response and complete disappearance of cutaneous rash. Unfortunately, the patient had several relapses of VL over the following years, though the interval between them has become wider after restarting maintenance therapy with L-AMB 4 mg/kg/day once a month. Even if rare, PKDL due to Leishmania infantum may occur in Western countries and represents a diagnostic and therapeutic challenge for physicians. The therapeutic management of both PKDL and VL in HIV infection is challenging, because relapses are frequent and evidence is often limited to small case series and case reports.

  4. Optimizing insecticide allocation strategies based on houses and livestock shelters for visceral leishmaniasis control in Bihar, India.

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    Gorahava, Kaushik K; Rosenberger, Jay M; Mubayi, Anuj

    2015-07-01

    Visceral leishmaniasis (VL) is the most deadly form of the leishmaniasis family of diseases, which affects numerous developing countries. The Indian state of Bihar has the highest prevalence and mortality rate of VL in the world. Insecticide spraying is believed to be an effective vector control program for controlling the spread of VL in Bihar; however, it is expensive and less effective if not implemented systematically. This study develops and analyzes a novel optimization model for VL control in Bihar that identifies an optimal (best possible) allocation of chosen insecticide (dichlorodiphenyltrichloroethane [DDT] or deltamethrin) based on the sizes of human and cattle populations in the region. The model maximizes the insecticide-induced sandfly death rate in human and cattle dwellings while staying within the current state budget for VL vector control efforts. The model results suggest that deltamethrin might not be a good replacement for DDT because the insecticide-induced sandfly deaths are 3.72 times more in case of DDT even after 90 days post spray. Different insecticide allocation strategies between the two types of sites (houses and cattle sheds) are suggested based on the state VL-control budget and have a direct implication on VL elimination efforts in a resource-limited region.

  5. Leishmania donovani Nucleoside Hydrolase (NH36) Domains Induce T-Cell Cytokine Responses in Human Visceral Leishmaniasis

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    Barbosa Santos, Micheli Luize; Nico, Dirlei; de Oliveira, Fabrícia Alvisi; Barreto, Aline Silva; Palatnik-de-Sousa, Iam; Carrillo, Eugenia; Moreno, Javier; de Luca, Paula Mello; Morrot, Alexandre; Rosa, Daniela Santoro; Palatnik, Marcos; Bani-Corrêa, Cristiane; de Almeida, Roque Pacheco; Palatnik-de-Sousa, Clarisa Beatriz

    2017-01-01

    Development of immunoprotection against visceral leishmaniasis (VL) focused on the identification of antigens capable of inducing a Th1 immune response. Alternatively, antigens targeting the CD8 and T-regulatory responses are also relevant in VL pathogenesis and worthy of being included in a preventive human vaccine. We assessed in active and cured patients and VL asymptomatic subjects the clinical signs and cytokine responses to the Leishmania donovani nucleoside hydrolase NH36 antigen and its N-(F1), central (F2) and C-terminal (F3) domains. As markers of VL resistance, the F2 induced the highest levels of IFN-γ, IL-1β, and TNF-α and, together with F1, the strongest secretion of IL-17, IL-6, and IL-10 in DTH+ and cured subjects. F2 also promoted the highest frequencies of CD3+CD4+IL-2+TNF-α−IFN-γ−, CD3+CD4+IL-2+TNF-α+IFN-γ−, CD3+CD4+IL-2+TNF-α−IFN-γ+, and CD3+CD4+IL-2+TNF-α+IFN-γ+ T cells in cured and asymptomatic subjects. Consistent with this, the IFN-γ increase was correlated with decreased spleen (R = −0.428, P = 0.05) and liver sizes (R = −0.428, P = 0.05) and with increased hematocrit counts (R = 0.532, P = 0.015) in response to F1 domain, and with increased hematocrit (R = 0.512, P 0.02) and hemoglobin counts (R = 0.434, P = 0.05) in response to F2. Additionally, IL-17 increases were associated with decreased spleen and liver sizes in response to F1 (R = −0.595, P = 0.005) and F2 (R = −0.462, P = 0.04). Conversely, F1 and F3 increased the CD3+CD8+IL-2+TNF-α−IFN-γ−, CD3+CD8+IL-2+TNF-α+IFN-γ−, and CD3+CD8+IL-2+TNF-α+IFN-γ+ T cell frequencies of VL patients correlated with increased spleen and liver sizes and decreased hemoglobin and hematocrit values. Therefore, cure and acquired resistance to VL correlate with the CD4+-Th1 and Th-17 T-cell responses to F2 and F1 domains. Clinical VL outcomes, by contrast, correlate with CD8+ T-cell responses against F3 and F1

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

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    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

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

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    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.

  8. Leishmania chagasi in Opossums (Didelphis albiventris) in an Urban Area Endemic for Visceral Leishmaniasis, Campo Grande, Mato Grosso do Sul, Brazil

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    Humberg, Roberta M. P.; Oshiro, Elisa T.; Cruz, Maria do Socorro Pires e; Ribolla, Paulo E. M.; Alonso, Diego P.; Ferreira, Alda M. T.; Bonamigo, Raquel A.; Tasso, Norton; de Oliveira, Alessandra Gutierrez

    2012-01-01

    We investigated the occurrence of Leishmania infantum chagasi in Didelphis albiventris opossums at a wild animal rehabilitation center in the city of Campo Grande, Brazil. A total of 54 opossums were tested for L. i. chagasi infection in peripheral blood and bone marrow samples. The samples were analyzed by direct examination, culturing in a specific medium, and polymerase chain reaction–restriction fragment length polymorphism. Leishmania i. chagasi DNA was detected by polymerase chain reaction–restriction fragment length polymorphism in 11 (20.37%) animals. A total of 81.81% of positive opossums were captured in areas of known visceral leishmaniasis transmission. These results suggest a role for D. albiventris in the urban transmission of visceral leishmaniasis. PMID:22802435

  9. Immunogenicity and Efficacy of Live L. tarentolae Expressing KMP11-NTGP96-GFP Fusion as a Vaccine Candidate against Experimental Visceral Leishmaniasis Caused by L. infantum

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    Vahid NASIRI

    2016-10-01

    Full Text Available Background: The aim of present study was to evaluate the protective efficacy of live recombinant L. tarentolae expressing KMP11-NTGP96-GFP fusion as candidates for live engineered recombinant vaccine against visceral leishmaniasis in BALB/c mice.Methods: KMP-11 and NT-GP96 genes cloned into the pJET1.2/blunt cloning vector and then into pEGFP-N1 expression vector. The KMP-11, NT-GP96 and GFP fused in pEGFP-N1 and subcloned into Leishmanian pLEXSY-neo vector. Finally this construct was transferred to L. tarentolae by electroporation. Tranfection was confirmed by SDS-PAGE, WESTERN blot, flowcytometry and RT-PCR. Protective efficacy of this construct was evaluated as a vaccine candidate against visceral leishmaniasis. Parasite burden, humoral and cellular immune responses were assessed before and at 4 weeks after challenge.Results: KMP- NT-Gp96-GFP Fusion was cloned successfully into pLEXSY -neo vector and this construct successfully transferred to L. tarentolae. Finding indicated that immunization with L. tarentolae tarentolae-KMP11-NTGP96-GFP provides significant protection against visceral leishmaniasis and was able to induce an increased expression of IFN-γ and IgG2a. Following challenge, a reduced parasite load in the spleen of the KMP11-NTGP96-GFP immunized group was detected.Conclusion: The present study is the first to use a combination of a Leishmania antigen with an immunologic antigen in live recombinant L. tarentolae and results suggest that L. tarentolae-KMP11-NTGP96-GFP could be considered as a potential tool in vaccination against visceral leishmaniasis and this vaccination strategy could provide a potent rout for future vaccine development. 

  10. Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial.

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    Wasunna, M; Njenga, S; Balasegaram, M.; Alexander, N; Omollo, R; Edwards, T.; Dorlo, TP; Musa, B; Ali, MH; Elamin, MY; Kirigi, G; Juma, R; Kip, AE; Schoone, GJ; Hailu, A.

    2016-01-01

    BACKGROUND: SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. METHODS: A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three...

  11. Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial

    OpenAIRE

    Wasunna, Monique; Njenga, Simon; Balasegaram, Manica; Alexander, Neal; Omollo, Raymond; Edwards, Tansy; Dorlo, Thomas P.C.; Musa, Brima; Ali, Mohammed Hassan Sharaf; Elamin, Mohammed Yasein; Kirigi, George; Juma, Rashid; Kip, Anke E; Schoone, Gerard J.; Hailu, Asrat

    2016-01-01

    Background SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. Methods A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three t...

  12. Predicting the geographic distribution of Lutzomyia longipalpis (Diptera: Psychodidae) and visceral leishmaniasis in the state of Mato Grosso do Sul, Brazil

    OpenAIRE

    Paulo Silva de Almeida; Alan Sciamarelli; Paulo Mira Batista; Ademar Dimas Ferreira; Joao Nascimento; Josue Raizer.; Jose Dilermando Andrade Filho; Rodrigo Gurgel-Goncalves

    2013-01-01

    To understand the geographic distribution of visceral leishmaniasis (VL) in the state of Mato Grosso do Sul (MS), Brazil, both the climatic niches of Lutzomyia longipalpis and VL cases were analysed. Distributional data were obtained from 55 of the 79 counties of MS between 2003-2012. Ecological niche models (ENM) of Lu. longipalpis and VL cases were produced using the maximum entropy algorithm based on eight climatic variables. Lu. longipalpis showed a wide distribution in MS. The highest cl...

  13. 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

    DEFF Research Database (Denmark)

    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...... in five of 17 samples from cured patients. Four of the five responding cultures produced IL-4, i.e. the response to this antigen was of the Th2 type. Furthermore, sera from acutely ill visceral leishmaniasis patients contained high levels of IgG antibodies to gp63. The Th2-like response to gp63...... in patients cured of visceral leishmaniasis differs from the Th1-like response to the same antigen observed in patients cured of cutaneous leishmaniasis....

  14. Vaccines for Canine Leishmaniasis

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    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.

  15. Seasonality of sand flies (Diptera: Psychodidae) and Leishmania DNA detection in vector species in an area with endemic visceral leishmaniasis

    Science.gov (United States)

    Saraiva, Lara; Leite, Camila Gonçalves; Lima, Ana Cristina Vianna Mariano da Rocha; de Carvalho, Luiz Otávio Alves; Pereira, Agnes Antônia Sampaio; Rugani, Jerônimo Marteleto Nunes; Rego, Felipe Dutra; Gontijo, Célia Maria Ferreira; Andrade, José Dilermando

    2017-01-01

    BACKGROUND Leishmaniases are a serious health problem in southeast Brazil, including the city of Belo Horizonte (BH), Minas Gerais state (MG), where there are high rates of incidence and mortality due to visceral leishmaniases. BH is divided into nine sanitary districts (SD) of which one, the Venda Nova SD, was selected for this study because it has high rates of positivity for canine leishmaniasis and high incidence of human leishmaniasis. OBJECTIVES This study aimed to survey the sand fly fauna in Venda Nova SD from August 2011 to July 2013 and perform a descriptive analysis of the vector population. METHODS The sampling was carried out using automatic HP light traps at all covered areas of the Venda Nova SD, in a total of eighteen light traps. Sampled specimens were identified following Galati (2003), and females were submitted to molecular techniques for the detection and identification of Leishmania DNA. A simple environmental description was done for it area and Kernel estimation was used to infer vector density for each study site. FINDINGS A total of 2,427 sand fly specimens belonging to eight species and five genera were collected of which 95.3% were Lutzomyia longipalpis. The seasonal variation curve was delineated by this species. Lu. longipalpis was the most abundant at all collection points and in all months of the study, and exhibited a natural infection rate of 1.01% for Leishmania infantum and 1.77% for Leishmania braziliensis. MAIN CONCLUSIONS The results show the presence and adaptation of Lu. longipalpis to the anthropic environment of BH and reinforces its role as the main vector of L. infantum in the region. PMID:28327794

  16. Visceral Leishmaniasis on the Indian Subcontinent: Modelling the Dynamic Relationship between Vector Control Schemes and Vector Life Cycles

    Science.gov (United States)

    2016-01-01

    Background Visceral leishmaniasis (VL) is a disease caused by two known vector-borne parasite species (Leishmania donovani, L. infantum), transmitted to man by phlebotomine sand flies (species: Phlebotomus and Lutzomyia), resulting in ≈50,000 human fatalities annually, ≈67% occurring on the Indian subcontinent. Indoor residual spraying is the current method of sand fly control in India, but alternative means of vector control, such as the treatment of livestock with systemic insecticide-based drugs, are being evaluated. We describe an individual-based, stochastic, life-stage-structured model that represents a sand fly vector population within a village in India and simulates the effects of vector control via fipronil-based drugs orally administered to cattle, which target both blood-feeding adults and larvae that feed on host feces. Principle findings Simulation results indicated efficacy of fipronil-based control schemes in reducing sand fly abundance depended on timing of drug applications relative to seasonality of the sand fly life cycle. Taking into account cost-effectiveness and logistical feasibility, two of the most efficacious treatment schemes reduced population peaks occurring from April through August by ≈90% (applications 3 times per year at 2-month intervals initiated in March) and >95% (applications 6 times per year at 2-month intervals initiated in January) relative to no control, with the cumulative number of sand fly days occurring April-August reduced by ≈83% and ≈97%, respectively, and more specifically during the summer months of peak human exposure (June-August) by ≈85% and ≈97%, respectively. Conclusions Our model should prove useful in a priori evaluation of the efficacy of fipronil-based drugs in controlling leishmaniasis on the Indian subcontinent and beyond. PMID:27537774

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  18. Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs

    Science.gov (United States)

    Avishek, Kumar; Kaushal, Himanshu; Gannavaram, Sreenivas; Dey, Ranadhir; Selvapandiyan, Angamuthu; Ramesh, V.; Negi, Narender Singh; Dubey, Uma S.; Nakhasi, Hira L.; Salotra, Poonam

    2016-01-01

    Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1−/− and Ldp27−/−) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1−/− and Ldp27−/− in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1−/− and Ldp27−/− strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4+ and CD8+ T cells and IL-17 secreting CD4+ cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1−/− and Ldp27−/− are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure. PMID:27624408

  19. Nasal, oral and ear swabs for canine visceral leishmaniasis diagnosis: new practical approaches for detection of Leishmania infantum DNA.

    Directory of Open Access Journals (Sweden)

    Sidney de Almeida Ferreira

    Full Text Available BACKGROUND: The aim of this study was to evaluate the potential use of nasal, oral, and ear swabs for molecular diagnosis of canine visceral leishmaniasis (CVL in an endemic urban area in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-two naturally infected and ten healthy dogs were enrolled in this study. Bone marrow aspirates, peripheral blood, skin biopsy, and conjunctival, nasal, oral, and ear swabs were collected. All samples, except blood, were submitted to conventional PCR (cPCR and quantitative real time PCR (qPCR to detect and quantify Leishmania infantum DNA, respectively. All dogs were submitted to thorough clinical analysis and were included based on a combination of serological (ELISA immunoassay and immunofluorescent antibody test and parasitological methods. The cPCR positivity obtained from nasal swab samples was 87% (54/62, equivalent to those from other samples (P>0.05. Positive results were obtained for 79% (22/28 in oral swabs and 43% (12/28 in ear swab samples. A significant difference was observed between these data (P=0.013, and the frequency of positive results from oral swab was equivalent to those from other samples (P>0.05. The use of ear swab samples for cPCR assays is promising because its result was equivalent to skin biopsy data (P>0.05. The qPCR data revealed that parasite loads in mucosal tissues were similar (P>0.05, but significantly lower than the parasite burden observed in bone marrow and skin samples (P<0.05. CONCLUSIONS: Nasal and oral swab samples showed a high potential for the qualitative molecular diagnosis of CVL because their results were equivalent to those observed in samples collected invasively. Considering that mucosae swab collections are painless, noninvasive, fast and practical, the combination of these samples would be useful in massive screening of dogs. This work highlights the potential of practical approaches for molecular diagnosis of CVL and human leishmaniasis infections.

  20. Post Kala-Azar dermal leishmaniasis following treatment with 20 mg/kg liposomal amphotericin B (Ambisome for primary visceral leishmaniasis in Bihar, India.

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    Sakib Burza

    Full Text Available BACKGROUND: The skin disorder Post Kala-Azar Dermal Leishmaniasis (PKDL occurs in up to 10% of patients treated for visceral leishmaniasis (VL in India. The pathogenesis of PKDL is not yet fully understood. Cases have been reported in India following therapy with most available treatments, but rarely in those treated with liposomal amphotericin B (Ambisome. Between July 2007 and August 2012 with the support of the Rajendra Memorial Research Institute (RMRI, Médecins Sans Frontières (MSF supported a VL treatment programme in Bihar, India-an area highly endemic for Leishmania donovani-in which 8749 patients received 20 mg/kg intravenous Ambisome as first-line treatment. This study describes the characteristics of patients who returned to the MSF supported treatment programme with PKDL. METHODS AND PRINCIPAL FINDINGS: Over a 5-year period, Ambisome was administered to 8749 patients with laboratory-confirmed VL (clinical signs, rK39 positive, with/without parasite confirmation in four intravenous doses of 5 mg/kg to a total of 20 mg/kg, with a high initial-cure rate (99.3% and low default rate (0.3%. All patients received health education highlighting the possibility and symptoms of developing PKDL, and advice to return to the MSF programme if these symptoms developed. This is an observational retrospective cohort study of the programme outcomes. Of the 8311 patients completing treatment for their first episode of VL, 24 (0.3% returned passively to the programme complaining of symptoms subsequently confirmed as PKDL, diagnosed from clinical history, appearance consistent with PKDL, and slit-skin smear examination. Of the 24 patients, 89% had macular lesions, with a median time (interquartile range to development of 1.2 (0.8-2.2 years following treatment. Comparison of the demographic and clinical characteristics of the VL patients treated with Ambisome who later developed PKDL, with those of the remaining cohort did not identify any significant

  1. Decrease of the incidence of human and canine visceral leishmaniasis after dog vaccination with Leishmune in Brazilian endemic areas.

    Science.gov (United States)

    Palatnik-de-Sousa, Clarisa B; Silva-Antunes, Ilce; Morgado, Adilson de Aguiar; Menz, Ingrid; Palatnik, Marcos; Lavor, Carlile

    2009-06-02

    Leishmune, the first prophylactic vaccine licensed against canine visceral leishmaniasis (CVL), has been used in Brazil since 2004, where seropositive dogs are sacrificed in order to control human visceral leishmaniasis (VL). We demonstrate here that vaccination with Leishmune does not interfere with the serological control campaign (110,000 dogs). Only 1.3% of positivity (76 among 5860) was detected among Leishmune uninfected vaccinees. We also analyzed the possible additive effect of Leishmune vaccination over dog culling, on the decrease of the incidence of CVL and VL in two Brazilian endemic areas, from 2004 to 2006. In Araçatuba, a 25% of decline was seen in CVL with a 61% decline in human cases, indicating the additive effect of Leishmune vaccination of 5.7% of the healthy dogs (1419 dogs), on regular dog culling. In Belo Horizonte (BH), rising curves of canine and human incidence were observed in the districts of Barreiro, Venda Nova and Noroeste, while the canine and human incidence of Centro Sul, Leste, Nordeste, Norte, Pampulha and Oeste, started to decrease or maintained a stabilized plateau after Leishmune vaccination. Among the districts showing a percent decrease of human incidence (-36.5%), Centro Sul and Pampulha showed the highest dog vaccination percents (63.27% and 27.27%, respectively) and the lowest dog incidence (-3.36% and 1.89%, respectively). They were followed by Oeste, that vaccinated 25.30% of the animals and experienced an increase of only 12.86% of dog incidence and by Leste and Nordeste, with lower proportions of vaccinees (11.72% and 10.76%, respectively) and probably because of that, slightly higher canine incidences (42.77% and 35.73%). The only exception was found in Norte district where the reduced human and canine incidence were not correlated to Leishmune vaccination. Much lower proportions of dogs were vaccinated in Venda Nova (4.35%), Noroeste (10.27%) and Barreiro (0.09%) districts, which according to that exhibited very

  2. Magnitude of visceral leishmaniasis and poor treatment outcome among HIV patients: meta-analysis and systematic review

    Directory of Open Access Journals (Sweden)

    Alemayehu M

    2016-03-01

    Full Text Available Mekuriaw Alemayehu,1 Mamo Wubshet,1 Nebiyu Mesfin,2 1Environmental and Occupational Health and Safety Department, Institute of Public Health, 2Internal Medicine Department, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Background: Visceral leishmaniasis (VL coinfection with HIV/AIDS most often results in unfavorable responses to treatment, frequent relapses, and premature deaths. Scarce data are available, regarding the magnitude and poor treatment outcomes of VL-HIV coinfection. Objective: The main objective of this systematic review was to describe the pooled prevalence of VL and poor treatment outcome among HIV patients. Review methods: Electronic databases mainly PubMed were searched. Databases, such as Google and Google scholar, were searched for gray literature. Articles were selected based on their inclusion criterion, whether they included HIV-positive individuals with VL diagnosis. STATA 11 software was used to conduct a meta-analysis of pooled prevalence of VL-HIV coinfection. Results: Fifteen of the 150 articles fulfilled the inclusion criteria. A majority of the study participants were males between 25 years and 41 years of age. The pooled prevalence of VL-HIV coinfection is 5.2% with 95% confidence interval of (2.45–10.99. Two studies demonstrated the impact of antiretroviral treatment on reduction in relapse rate compared with patients who did not start antiretroviral treatment. One study showed that the higher the baseline CD4+ cell count (>100 cells/mL the lower the relapse rate. Former VL episodes were identified as risk factors for relapse in two articles. In one of the articles, an earlier bout of VL remains significant in the model adjusted to other variables. Conclusion: The pooled prevalence of VL in HIV-infected patients is low and an earlier bout of VL and CD4+ count <100 cells/mL at the time of primary VL diagnosis are factors that predict poor treatment outcome

  3. A Vaccine Therapy for Canine Visceral Leishmaniasis Promoted Significant Improvement of Clinical and Immune Status with Reduction in Parasite Burden

    Science.gov (United States)

    Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Reis, Levi Eduardo Soares; Cardoso, Jamille Mirelle de Oliveira; Mathias, Fernando Augusto Siqueira; de Brito, Rory Cristiane Fortes; da Silva, Sydnei Magno; Gontijo, Nelder De Figueiredo; Ferreira, Sidney de Almeida; Valenzuela, Jesus G.; Corrêa-Oliveira, Rodrigo; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa

    2017-01-01

    Herein, we evaluated the treatment strategy employing a therapeutic heterologous vaccine composed of antigens of Leishmania braziliensis associated with MPL adjuvant (LBMPL vaccine) for visceral leishmaniasis (VL) in symptomatic dogs naturally infected by Leishmania infantum. Sixteen dogs received immunotherapy with MPL adjuvant (n = 6) or with a vaccine composed of antigens of L. braziliensis associated with MPL (LBMPL vaccine therapy, n = 10). Dogs were submitted to an immunotherapeutic scheme consisting of 3 series composed of 10 subcutaneous doses with 10-day interval between each series. The animals were evaluated before (T0) and 90 days after treatment (T90) for their biochemical/hematological, immunological, clinical, and parasitological variables. Our major results showed that the vaccine therapy with LBMPL was able to restore and normalize main biochemical (urea, AST, ALP, and bilirubin) and hematological (erythrocytes, hemoglobin, hematocrit, and platelets) parameters. In addition, in an ex vivo analysis using flow cytometry, dogs treated with LBMPL vaccine showed increased CD3+ T lymphocytes and their subpopulations (TCD4+ and TCD8+), reduction of CD21+ B lymphocytes, increased NK cells (CD5−CD16+) and CD14+ monocytes. Under in vitro conditions, the animals developed a strong antigen-specific lymphoproliferation mainly by TCD4+ and TCD8+ cells; increasing in both TCD4+IFN-γ+ and TCD8+IFN-γ+ as well as reduction of TCD4+IL-4+ and TCD8+IL-4+ lymphocytes with an increased production of TNF-α and reduced levels of IL-10. Concerning the clinical signs of canine visceral leishmaniasis, the animals showed an important reduction in the number and intensity of the disease signs; increase body weight as well as reduction of splenomegaly. In addition, the LBMPL immunotherapy also promoted a reduction in parasite burden assessed by real-time PCR. In the bone marrow, we observed seven times less parasites in LBMPL animals compared with MPL group. The

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

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    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

    Directory of Open Access Journals (Sweden)

    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. Outbreak of autochthonous canine visceral leishmaniasis in Santa Catarina, Brazil Surto autóctone de leishmaniose visceral canina no Estado de Santa Catarina

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    Mário Steindel

    2013-04-01

    Full Text Available The present study reports the first outbreak of autochthonous canine visceral leishmaniasis in Florianópolis, Santa Catarina, southern Brazil. Following the report of two cases of CVL, the Control Center of Zoonotic Diseases conducted a serological survey by ELISA and IFAT assays in seven districts of the Santa Catarina Island. Eleven seropositive dogs of autochthonous transmission were used in the present study. Infection by Leishmania sp. was confirmed by parasitological examination of bone marrow, liver, spleen and lymph nodes, culture in Schneider's medium and PCR. Leishmania sp. isolates were characterized by PCR-RFLP and hybridization with specific probes, allowing for the identification of Leishmania infantum. Autochthonous transmission of this disease in an area with high tourist traffic presents a major public health concern and signifies the emergence of an important zoonosis in southern Brazil. Therefore, the implementation of surveillance and control measures is imperative to prevent the spread of the disease among the canine population as well as transmission to the human population.O presente estudo relata o primeiro surto autóctone de leishmaniose visceral canina (LCV em Florianópolis, Santa Catarina, Brasil. Durante levantamento soro-epidemiológico realizado pelo Centro de Controle de Doenças Zoonóticas (CCZ envolvendo 2.124 cães, 29 (1,37% foram soropositivos para VL (ELISA + RIFI. Onze cães positivos por transmissão autóctone foram utilizados no presente estudo. A confirmação da infecção por Leishmania sp. foi realizada pelo exame parasitológico da medula óssea, fígado, baço e linfonodos, cultura em meio Schneider e PCR. Os isolados de Leishmania sp. foram caracterizados por PCR-RFLP e hibridação com sondas específicas, permitindo a identificação de Leishmania infantum. A transmissão autóctone da LCV em uma área com grande fluxo turístico como Florianópolis representa um preocupante risco à saúde p

  7. The experimental chemotherapy of leishmaniasis, IV. The development of a rodent model for visceral infection.

    Science.gov (United States)

    Trotter, E R; Peters, W; Robinson, B L

    1980-04-01

    A description is given of two methods for investigating the action of drugs against a viscerotropic Leishmania in mice. The parasite employed was isolated from a patient with kala-azar in Ethiopia. It is designated 'L. infantum LV9' and produces a visceral infection in NMRI mice. The biochemical typing characters of the parasite are described. In Method A, infected animals were treated from the 5th or 6th day after infection (D + 5 or D + 6) for five consecutive days. They were sacrificed 24 hours after the completion of drug treatment and an estimate was made of the amastigote load in the liver. A comparison of this with untreated controls gives an index of activity of a test drug, from 0 to 3. Method B is similar except that the ED50 and ED90 are determined by graphic analysis of data from graded drug doses. A comparison is made with sodium stibogluconate used as a positive drug control to yield a 'Pentostam Index'. The course of infection in BALB/c and NMRI mice is compared with that in random-bred Swiss mice in which 'L. infantum LV9' produces an inconsistent infection. An inoculum of 10(7) amastigotes produces a peak parasite intensity between D + 15 and D + 20. The ED50 and ED90 of sodium stibogluconate (Pentostam) (as Sbv) in Method B are 22 x 5 and 46 x 5 mg/kg sc daily x 5. (By Method A the single dose figures are 65 and 280 mg/kg.) For routine use a standard dose level of 120 mg/kg sc daily x 5 of Pentostam (Sbv) is used in Method B. The ED50 and ED90 of meglumine antimoniate (Glucantime) (as Sbv) in Method B are 11 x 6 and 66 x 7 mg/kg sc daily x 5. Data are given for other antimonials in Method A. Pentamidine and diminazene aceturate proved to have a slow action which was more readily demonstrated if the observation period was prolonged. Amphotericin B was moderately active but toxic to the host. The relevance of these models and a comparison of data found in the mouse and hamster are debated.

  8. Natural autoantibodies, IgG antibodies to tetanus toxoid and CD5+ B cells in patients with Mediterranean visceral leishmaniasis. The Leishmania Study Group.

    Science.gov (United States)

    Louzir, H; Belal-Kacemi, L; Sassi, A; Laouini, D; Ben Ismail, R; Dellagi, K

    1994-03-01

    Natural autoantibodies (NaAb) and IgG antibodies to tetanus toxoid (TT) were analysed in the sera of 38 children with active visceral leishmaniasis (VL) previously vaccinated with TT and in 30 healthy controls matched for sex and age. Patients exhibited high levels of NaAb to a panel of self antigens (tubulin, myosin, myoglobin, actin) contrasting to a low level of IgG to TT. Analysis of the circulating B cells in 26 untreated patients showed a low percentage of CD5+ per total B cells (3-66%, mean 36.6%) compared with 14 normal controls (17.8-66.6%, mean 52.7%) (P < 0.001). Evaluation of these parameters after antimonial therapy showed a significant decrease of the level of the NaAb (P < 0.0005), and a spontaneous increase of the level of the IgG to TT without any vaccine boosting (P < 0.01). In contrast, there was a significant increase in CD5+ B cells (P < 0.0005). This result suggests that CD5+ B cells may be sequestrated in parasitized lymphoid organs and may be released after remission. These findings show that the polyclonal B cell activation that occurs during active VL involves mainly B cells bearing NaAb and are in favour of a functional dichotomy of B cells.

  9. Dispersal of Lutzomyia longipalpis and expansion of canine and human visceral leishmaniasis in São Paulo State, Brazil.

    Science.gov (United States)

    Oliveira, Agda Maria; Vieira, Carolina Portugal; Dibo, Margareth Regina; Guirado, Marluci Monteiro; Rodas, Lilian Aparecida Colebrusco; Chiaravalloti-Neto, Francisco

    2016-12-01

    Visceral leishmaniasis (VL), a neglected disease, is a serious public health problem that affects millions of people worldwide. The objectives of the study were to evaluate the sensitivity of Lutzomyia longipalpis and canine VL (CVL) autochthony early detection and describe the spatial and temporal dispersal of vector and expansion of VL in a Brazilian state. We obtained data on the leishmaniasis vector and VL cases in São Paulo State (SP), Brazil, from the Division of Endemic Disease Control and from the Epidemiological Surveillance Center of the São Paulo State Department of Health. Data were analyzed for 645 municipalities and 63 microregions and presented as thematic and flow maps. Following the verified presence of L. longipalpis in Araçatuba in 1997, the first autochthonous cases of canine VL (CVL) (1998) and of human VL (HVL) (1999) in São Paulo were reported, both in Araçatuba. From 1997 to 2014, the urban presence of the leishmaniasis vector was verified in 167 (25.9%) municipalities with cases of CVL reported in 108 (16.7%) and cases of HVL in 84 (13%). The sensitivities for vector presence early detection in relation to the identification of CVL and HVL autochthony were, respectively, equal to 76.4 and 92.5%. The sensitivity for CVL autochthony early detection in relation to the HVL autochthony identification was 75.8%. Vector dispersal and expansion of CVL and HVL were from the northwest to the southeast of the state, primarily flanking the Marechal Rondon highway at a constant rate of progression of 10, seven, and six new municipalities affected per year, respectively. We concluded that the sensitivity for vector presence and CVL autochthony presented reasonable accuracy and most of the time the vector presence and, specially, the CVL and HVL autochthony were identified in the main cities of the microregions of SP. Vector dispersal and expansion of VL started in 1997 near the state border of SP with the state of Mato Grosso do Sul. It has advanced

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

    OpenAIRE

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

    2006-01-01

    The P-8 proteoglycolipid complex (P-8 PGLC), an amastigote antigen of L. 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 L. infantum infected dogs. In this study, it is shown that PBMC from experimentally infected dogs (as...

  11. General false positive ELISA reactions in visceral leishmaniasis. Implications for the use of enzyme immunoassay analyses in tropical Africa.

    Science.gov (United States)

    Elshafie, Amir I; Mullazehi, Mohammed; Rönnelid, Johan

    2016-04-01

    Leishmaniasis is a neglected disease in tropical countries. Clinical and laboratory features may mimic autoimmune diseases and this can complicate the Leishmania diagnosis. Due to our previous investigation for false anti-CCP2 reactivity in Leishmania-infected subjects and our interest in immunity against the joint-specific collagen type II (CII) in rheumatoid arthritis (RA) we investigated the same cohort for anti-CII antibodies. We found elevated anti-CII reactivity in Leishmania-infected patients as compared to controls. When anti-CII OD values were compared with BSA-blocked control plates we found higher reactivity against BSA than in CII-coated plates in many Leishmania-infected patients. The percentage of such false positive anti-CII reactions increased with inflammatory activity, and was found in almost all Leishmania patients with highly active inflammatory disease, but was as low in Sudanese healthy controls as well as among Swedish RA patients. The correlation coefficients between false positive anti-CII and anti-CCP2 measured with a commercial ELISA were highest for patients with the most inflammatory disease but non-significant for Sudanese controls and Swedish RA patients, arguing that our findings may have general implications for ELISA measurements in leishmaniasis. ELISA investigations in areas endemic for leishmaniasis might benefit from individual-specific control wells for each serum sample. This approach might also be applicable to other geographical areas or patient groups with high incidence of inflammatory and infectious diseases.

  12. A current perspective on leishmaniasis

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    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.

  13. A Current Perspective on Leishmaniasis

    Science.gov (United States)

    Clem, Angela

    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 and possible vaccines for leishmaniasis were reviewed in this article. PMID:20606967

  14. Levels of mannose-binding lectin in individuals with visceral leishmaniasis in the northeast region of Brazil.

    Science.gov (United States)

    da Silva, E L; Campos Júnior, M; Monteiro, S G; Costa, G C; Magalhães, A L P; Santos, M D C; Caldas, A J M; Pimentel, M M G

    2015-12-29

    Visceral leishmaniasis (VL) is one of the seven priority endemic diseases in the world. The clinical outcome of many infections is not only dependent on the pathogenic organism, but also on the genetic variability of the host susceptibility to infection. Mannose-binding lectin (MBL) is a protein that plays an important role in the innate immune system. The aim of this study was to compare the serum levels of MBL between healthy controls and carriers of VL. The VL cases were recruited randomly from the main hospitals and referral outpatient clinics for VL in São Luís, and from home visits. Determination of MBL protein levels was performed by enzyme-linked immunosorbent assay. Of the 161 patients with VL and the 161 healthy controls, 60.9 and 67.1% had high levels of MBL, respectively. There was no significant difference in MBL levels between cases and controls. Low socioeconomic status and living conditions are conducive to the occurrence of VL. Owing to the small number of existing studies, it is extremely important to conduct further studies on MBL levels and susceptibility to VL, especially in regions where the disease is endemic, such as Maranhão, Brazil.

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

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    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.

  16. Validity of the polymerase chain reaction in the diagnosis of clinically suspected cases of American visceral leishmaniasis.

    Science.gov (United States)

    Pedrosa, Celia Maria Silva; Ximenes, Ricardo Arraes de Alencar; Almeida, Wendell Alexandre Pinheiro de; Rocha, Eliana Maria Mauricio da

    2013-01-01

    To test the validity of the polymerase chain reaction for diagnosing American visceral leishmaniasis, 88 suspected cases were studied. Diagnosis was confirmed in 47 (53.5%) and ruled out in 41 (46.5%) patients. Samples of bone marrow and peripheral blood were processed by polymerase chain reaction to evaluate the sensitivity and specificity of the test and its agreement beyond chance with microscopy examination. The polymerase chain reaction was positive in bone marrow of 100% of the patients with amastigotes seen with microscopy examination, and in 59.5% in those where no parasite were seen. Agreement beyond chance between visualization of the parasite in bone marrow aspirates and polymerase chain reaction was considered weak (Kappa=0.41). Concordance between polymerase chain reaction of bone marrow aspirates and of peripheral blood was considered excellent (Kappa=0.88). The test turned out positive in all bone marrow aspirates of those with the disease and whereas the positivity rate was 58.5% among those without the disease, with specificity rate of 41.5%.

  17. [Liposomal Amphotericin B for treatment of acute phase and secondary prophylaxis of visceral leishmaniasis in a HIV positive patient

    Science.gov (United States)

    Murdaca, G.; Setti, M.; Campelli, A.; Ghio, M.; Puppo, F.; Indiveri, F.

    2000-01-01

    The authors describe a clinical case of an HIV+, HBV+ and HCV+ 46-year-old male patient, with a history of drug abuse of intravenous heroin, admitted to their attention for high remittent fever (39 C), weight loss and severe dysphonia. The increasing severity of dysphonia had required a fiberlaryngoscopic examination which allowed a diagnosis of hypertrophy of vocal chords. The Wright-Giemsa stain performed on vocal chord biopsy evidenced Leishmania infantum. The same protozoon was subsequently also revealed in bone marrow aspirate. The patient underwent a course of therapy with Amphotericin B deoxycolate (0.5 mg/kg) which had to be interrupted due to insurgence of diffuse petechiae and switched to Amphotericin in cholesterinic suspension (2.5 mg/kg every 21 days). After three months, insurgence of high fever related to the infusion induced the start of therapy with liposomal Amphotericin B (3 mg/kg every 28 days) which led in 4 weeks to a complete clinical remission. Prophylaxis with liposomal Amphotericin B is continuing and remission has persisted for 40 months. This case report shows the importance of liposomal Amphotericin B therapy in order either to obtain clinical remission of visceral leishmaniasis or, in secondary prophylaxis, to reduce the risk of the disease's recurrence.

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

    Science.gov (United States)

    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.

  19. The fucose-mannose ligand-ELISA in the diagnosis and prognosis of canine visceral leishmaniasis in Brazil.

    Science.gov (United States)

    Cabrera, G P; Da Silva, V O; Da Costa, R T; Reis, A B; Mayrink, W; Genaro, O; Palatnik-de-Sousa, C B

    1999-08-01

    The fucose-mannose ligand (FML)-ELISA assay showed a sensitivity of 100% and a specificity of 100% in diagnosis of canine visceral leishmaniasis (CVL) (kala-azar) in sera from naturally infected dogs from São Gonçalo do Amaranto, Rio Grande de Norte, Brazil. The overall prevalence of antibodies to Leishmania in the endemic area was 23% (79 of 343). Seroreactivity detected by a Leishmania chagasi immunofluorescent (IF) assay was much lower (2.9%) and similar to the percentage of dogs with kala-azar symptoms (2.6%). Twenty-one of 21 asymptomatic, FML-seropositive animals died of kala-azar in a period ranging from 0 to 6 months after diagnosis. The predictive value was 100% for the FML-ELISA, 43% for an L. mexicana ELISA, and 24% for the L. mexicana and L. chagasi IF assays, respectively. In experimentally infected dogs, all assays detected seropositivity between 90 and 120 days after infection. Since the current strategy for control of CVL is based on detection and destruction of infected dogs, the highly predictive, sensitive, and specific FML-ELISA represents a useful tool for field control of the disease.

  20. Canine visceral leishmaniasis in the metropolitan area of São Paulo: Pintomyia fischeri as potential vector of Leishmania infantum.

    Science.gov (United States)

    Galvis-Ovallos, Fredy; da Silva, Mariana Dantas; Bispo, Giulia Baldaconi da Silva; de Oliveira, Alessandra Gutierrez; Neto, José Rodriguez Gonçalves; Malafronte, Rosely Dos Santos; Galati, Eunice Aparecida Bianchi

    2017-01-01

    American visceral leishmaniasis is a zoonosis caused by Leishmania infantum and transmitted mainly by Lutzomyia longipalpis. However, canine cases have been reported in the absence of this species in the Greater São Paulo region, where Pintomyia fischeri and Migonemyia migonei are the predominant species. This raises the suspicion that they could be acting as vectors. Therefore, this study sought to investigate specific vector capacity parameters of these species and to compare them with those of Lu. longipalpis s.l. Among these parameters the blood feeding rate, the survival, and the susceptibility to the development of Le. infantum were evaluated for the three species, and the attractiveness of dogs to Pi. fischeri and Mg. migonei was evaluated. The estimated interval between blood meals was shorter for Lu. longipalpis s.l, followed by Pi. fischeri and Mg. migonei. The infection rate with Le. infantum flagellates in Lu. longipalpis was 9.8%, in Pi. fischeri 4.8%, and in Mg. migonei nil. The respective infective life expectancies (days) of Lu. longipalpis, Mg. migonei, and Pi. fischeri were 2.4, 1.94, and 1.68. Both Pi. fischeri and Mg. migonei were captured in the kennel with a predominance (95%) of Pi. fischeri. Considering the great attractiveness of dogs to Pi. fischeri, its susceptibility to infection by Le. infantum, infective life expectancies, and predominance in Greater São Paulo, this study presents evidence of Pi. fischeri as a potential vector of this parasite in the region.

  1. Evaluation of the vectorial capacity of Rhipicephalus sanguineus (Acari: Ixodidae) in the transmission of canine visceral leishmaniasis.

    Science.gov (United States)

    Paz, Gustavo Fontes; Ribeiro, Múcio Flávio Barbosa; Michalsky, Erika Monteiro; da Rocha Lima, Ana Cristina Vianna Mariano; França-Silva, João Carlos; Barata, Ricardo Andrade; Fortes-Dias, Consuelo Latorre; Dias, Edelberto Santos

    2010-01-01

    The vectorial capacity of Rhipicephalus sanguineus in the transmission of canine visceral leishmaniasis has been evaluated through a laboratory-controlled experiment. One healthy Leishmania-free dog and two dogs naturally infected with Leishmania were infested with R. sanguineus in various stages of development. Engorged larvae, unfed nymphs, engorged nymphs, unfed adults, engorged female adults and fed male adults were collected from the experimental animals and examined for Leishmania infection by optical microscopy, polymerase chain reaction (PCR) and parasite culture. Leishmania forms were not detected in any of the 433 smears prepared from engorged colonies nor in any of the 118 smears prepared from unfed colonies. However, one flagellate structure was identified in one of the smears. All pools of R. sanguineus that had fed on the infected dogs tested PCR-positive for Leishmania DNA, with the single exception of the pool of engorged larvae. In contrast, all pools of ticks that had fed on the Leishmania-free dog were PCR-negative. Leishmania growth was not observed in any of the tick colonies following incubation on culture medium. Considering that no Leishmania forms were identified in any of the meticulously analysed smears derived from engorged colonies of R. sanguineus, it appears somewhat unlikely that the maintenance and multiplication of Leishmania occurs within the tick.

  2. Histological study of cell migration in the dermis of hamsters after immunisation with two different vaccines against visceral leishmaniasis.

    Science.gov (United States)

    Moreira, Nádia das Dores; Giunchetti, Rodolfo Cordeiro; Carneiro, Cláudia Martins; Vitoriano-Souza, Juliana; Roatt, Bruno Mendes; Malaquias, Luiz Cosme Cotta; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

    2009-04-15

    Vaccine candidates, including live and/or killed parasites, Leishmania-purified fractions, defined recombinant antigens and antigen-encoding DNA-plasmids have been proposed to use as vaccine anti-Leishmania. More recently, the hamsters have been used to pre-selection of antigens candidate to apply in further experiments using canine model. In this report we evaluated the kinetics of cell migration in dermal inflammatory infiltrate, circulating leukocytes and the presence of nitric oxide (NO)/induced nitric oxide synthase during the early (1-24h) and late (48-168h) periods following inoculation of hamsters with antigenic components of anti-canine visceral leishmaniasis vaccines Leishmune and Leishmania braziliensis antigen (LB) with and without saponin (Sap) adjuvant. Our results show that LB caused an early reduction of lymphocytes in the dermis while Sap and LBSap triggered a late recruitment, suggesting the role of the adjuvant in the traffic of antigen-presenting cells and the induction of lymphocyte migration. In that manner our results suggest that the kinetics of cell migration on hamster model may be of value in the selection of vaccine antigens prior the tests in dogs particularly in respect of the toxicity of the preparations.

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

    Science.gov (United States)

    Oliveira, Everton Falcão de; Silva, Elaine Araújo e; Fernandes, Carlos Eurico dos Santos; Paranhos Filho, Antonio Conceição; Gamarra, Roberto Macedo; Ribeiro, Alisson André; Brazil, Reginaldo Peçanha; Oliveira, Alessandra Gutierrez de

    2012-05-01

    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.

  4. Transmission of visceral leishmaniasis in dogs in a risk area of the metropolitan region of Belo Horizonte, Minas Gerais, Brazil

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    E.G.P. Lopes

    Full Text Available ABSTRACT Visceral leishmaniasis (VL has spread rapidly across cities in the metropolitan region of Belo Horizonte. The aim of this study was to investigate VL dynamics in a prospective cohort study of dogs in Juatuba, between 2010 and 2011, to confirm the incidence of Leishmania infantum, and to assess possible risk factors associated with infection. An observational and prospective closed cohort study was performed using serology testing in dogs, randomly selected from the whole municipality. All seronegative dogs, or dogs with inconclusive results were monitored using indirect immunofluorescence (IIF at 6-month intervals. The dog's owners completed a semi-structured questionnaire to assess possible causal factors of seroconversion, and the responses were assessed using logistic regression. The canine incidence coefficient was 206/1,000 dogs per year (CI: 178-238, and a cluster was identified in an area with a high concentration of seropositive dogs, but a low overall canine population. Large dogs were identified as a risk factor and the following variables were identified as protection factors: dogs aged over 4 years, daily peridomicile cleaning, and better socioeconomic conditions. VL is spreading over a large area in Juatuba in a short period of time.

  5. Study of implementation and direct cost estimates for diagnostic tests for human visceral leishmaniasis in an urban area in Brazil

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    Tália Santana Machado de Assis

    2015-10-01

    Full Text Available Abstract This work reports the process and costs of comprehensively implementing two tests to decentralize the diagnosis of visceral leishmaniasis (VL in an endemic city in Brazil: a rapid test (IT LEISH and a direct agglutination test (DAT-LPC. The implementation began by training health professionals to perform the tests. Estimation of the training costs considered the proportional remuneration of all professionals involved and the direct costs of the tests used for training. The study was conducted between November 2011 and November 2013. During that time, 17 training sessions were held, and 175 professionals were trained. The training cost for each professional was US$ 7.13 for the IT LEISH and US$ 9.93 for the DAT-LPC. The direct costs of the IT LEISH and DAT-LPC were estimated to be US$ 6.62 and US$ 5.44, respectively. This first evaluation of the implementation of these diagnostic tests indicates the feasibility of decentralizing both methods to extend access to VL diagnosis in Brazil.

  6. Canine Visceral Leishmaniasis in Wild Canines (Fox, Jackal, and Wolf in Northeastern Iran Using Parasitological, Serological, and Molecular Methods

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    Mehdi Mohebali

    2016-10-01

    Full Text Available Background: Although many studies had been conducted on various aspects of canine visceral leishmaniasis (CVL in domestic dogs in the endemic areas of Iran, investigations on CVL in wild canines are rare.Methods: This is a cross-sectional study was conducted from December 2012 to 2013 in northeast of Iran where human VL is endemic. Wild canines were trapped around the areas where human VL cases had been previously identified. Wild canines were collected and examined both clinically and serologically using direct agglutination test (DAT. Microscopically examinations were performed in all the seropositive wild canines for the presence of the amastigote form of Leishmania spp. Some Leishmania sp. which had been isolated from the spleens of wild canines, were examined analyzed by conventional PCR and sequencing techniques using α-tubulin and GAPDH genes.Results: Altogether, 84 wild canines including foxes (Vulpes vulpes, n=21, Jackals (Canis aureus, n=60 and wolves (Canis lupus, n=3 were collected. Four foxes and seven jackals showed anti-Leishmania infantum antibodies with titers of 1:320–1:20480 in DAT. Furthermore, one fox and one jackal were parasitologically (microscopy and culture positive and L. infantum was confirmed by sequence analysis.Conclusion: The present study showed that sylvatic cycle of L. infantum had been established in the studied endemic areas of VL in northeastern Iran.

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

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    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.

  8. Occurrence of Lutzomyia longipalpis (Phlebotominae) and canine visceral leishmaniasis in a rural area of Ilha Solteira, SP, Brazil.

    Science.gov (United States)

    Spada, Julio Cesar Pereira; Silva, Diogo Tiago da; Martins, Kennya Rozy Real; Rodas, Lílian Aparecida Colebrusco; Alves, Maria Luana; Faria, Glaucia Amorim; Buzutti, Marcelo Costa; Silva, Hélio Ricardo; Starke-Buzetti, Wilma Aparecida

    2014-01-01

    This study aimed to investigate the occurrence of Lutzomyia longipalpis and also the canine visceral leishmaniasis (CVL) in a rural area of Ilha Solteira, state of São Paulo. Blood samples were collected from 32 dogs from different rural properties (small farms) and were analyzed by ELISA and the indirect immunofluorescence antibody test (IFAT) in order to diagnose CVL. From these serological tests, 31.25% of the dogs were positive for CVL and these were distributed in 66.7% (8/12) of the rural properties, which were positive for L. longipalpis. CDC (Center for Disease Control and Prevention) light traps were installed in 12 properties (one per property) and insects were caught on three consecutive days per month for one year. L. longipalpis was present on 100% of the rural properties visited, at least once during the twelve-month interval, totaling 64 males and 25 females. The insects were more numerous after the peak of the rain, but the association between prevalence of peridomestic vectors and the climatic data (precipitation, relative air humidity and temperature) and the occurrences of CVL among dogs on each rural property were not statistical significant (p <0.05). However, the occurrence of CVL cases in dogs and the presence of L. longipalpis indicate that more attention is necessairy for the control of this disease in the rural area studied.

  9. Phlebotomine sand flies in Porteirinha, an area of American visceral leishmaniasis transmission in the State of Minas Gerais, Brazil

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    Ricardo Andrade Barata

    2004-08-01

    Full Text Available A study of the phlebotomine sand fly fauna was carried out in an endemic area of American visceral leishmaniasis (AVL in the municipality of Porteirinha, in the Brazilian state of Minas Gerais. Captures were performed with CDC light traps in 7 districts, 5 days per month, during 2 consecutive years (January 2000 to December 2001. A total of 3240 sand flies were captured and identified. Sixteen species were found, among which 15 belonged to the genus Lutzomyia and one to the genus Brumptomyia. Lutzomyia longipalpis, a proven vector of AVL, was the predominant species (71.85% throughout the time period. The interference of climatic factors (temperature, humidity, and rainfall over the populational dynamics of the sand flies was determined. Statistical analysis of the data showed a significant correlation among the number of phlebotomine sand flies collected, rainfall, and humidity, whereas the effect of temperature was negligible, in that particular region. The amount of collected phlebotomine, the number of human cases, and the prevalence of canine AVL in the districts of Porteirinha are discussed.

  10. Occurrence of Lutzomyia longipalpis (Phlebotominae and canine visceral leishmaniasis in a rural area of Ilha Solteira, SP, Brazil

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    Julio Cesar Pereira Spada

    2014-12-01

    Full Text Available This study aimed to investigate the occurrence of Lutzomyia longipalpis and also the canine visceral leishmaniasis (CVL in a rural area of Ilha Solteira, state of São Paulo. Blood samples were collected from 32 dogs from different rural properties (small farms and were analyzed by ELISA and the indirect immunofluorescence antibody test (IFAT in order to diagnose CVL. From these serological tests, 31.25% of the dogs were positive for CVL and these were distributed in 66.7% (8/12 of the rural properties, which were positive for L. longipalpis. CDC (Center for Disease Control and Prevention light traps were installed in 12 properties (one per property and insects were caught on three consecutive days per month for one year. L. longipalpis was present on 100% of the rural properties visited, at least once during the twelve-month interval, totaling 64 males and 25 females. The insects were more numerous after the peak of the rain, but the association between prevalence of peridomestic vectors and the climatic data (precipitation, relative air humidity and temperature and the occurrences of CVL among dogs on each rural property were not statistical significant (p <0.05. However, the occurrence of CVL cases in dogs and the presence of L. longipalpis indicate that more attention is necessairy for the control of this disease in the rural area studied.

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

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    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.

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

    Institute of Scientific and Technical Information of China (English)

    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

  13. Leishmania infantum mimotopes and a phage-ELISA assay as tools for a sensitive and specific serodiagnosis of human visceral leishmaniasis.

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    Salles, Beatriz C S; Costa, Lourena E; Alves, Patrícia T; Dias, Ana C S; Vaz, Emília R; Menezes-Souza, Daniel; Ramos, Fernanda F; Duarte, Mariana C; Roatt, Bruno M; Chávez-Fumagalli, Miguel A; Tavares, Carlos A P; Gonçalves, Denise U; Rocha, Regina L; Goulart, Luiz R; Coelho, Eduardo A F

    2017-03-01

    Serological methods used to diagnose visceral leishmaniasis (VL) are considered minimally invasive, but they present problems related with their sensitivity and/or specificity. In this study, a subtractive selection using the phage display technology against antibodies from healthy subjects living in endemic and non-endemic areas of disease, as well as from Chagas disease patients and those developing active VL, was developed. The aim of this study was to select bacteriophage-fused epitopes to be used in the serodiagnosis of human VL. Eight phage clones were selected after the bio-panning rounds, and their reactivity was evaluated in a phage-ELISA assay against a human serological panel. A wild-type clone and the recombinant K39-based immunochromatographic test were used as controls. In the results, it was shown that all clones showed an excellent performance to serologically identify VL patients, demonstrating the feasibility of the isolated phages for developing a specific and sensitive serodiagnosis of human VL.

  14. 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

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    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.

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

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    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.

  16. A comparative evaluation of efficacy of chemotherapy, immunotherapy and immunochemotherapy in visceral leishmaniasis-an experimental study.

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    Joshi, Jyoti; Malla, Nancy; Kaur, Sukhbir

    2014-08-01

    Visceral leishmaniasis (VL) represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. Ninety per cent of VL cases occur in five countries namely Bangladesh, India, Nepal, Sudan and Brazil. No licensed vaccine is available till date against any form of leishmaniasis. High toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in VL endemic regions of the world. To combat this situation, immunochemotherapy can provide a solution. In the present study, an attempt has been made to assess the in vivo antileishmanial efficacy of chemotherapy, immunotherapy and immunochemotherapy with the use of a first generation antigen Killed Leishmania donovani (KLD) along with a standard drug sodium stibogluconate (SSG) and a newly tested antileishmanial cisplatin. Inbred BALB/c mice were infected with 10(7) promastigotes/0.1 ml of Leishmania donovani. A month after infection, these animals were given specific immunotherapy (KLD/KLD+MPL-A) or chemotherapy (SSG/cisplatin) or immunochemotherapy (SSG+KLD/SSG+KLD+MPL-A/cisplatin+KLD/cisplatin+KLD+MPL-A). Animals were sacrificed on 1, 15 and 30(th) day post treatment. The efficacy of these combinations was assessed in terms of parasite load and by immunological investigations. Infected mice and normal mice served as controls. Results showed that combination of drug and KLD significantly reduced the parasite burden, enhanced the DTH (Delayed Type Hypersensitivity) responses, showed increased levels of IgG2a and decreased levels of IgG1 as compared to mice given chemotherapy or immunotherapy alone. Further maximum protection was provided by SSG+KLD+MPL-A and it was most effective as depicted by 98.5% reduction in parasite load, a potent increase in IFN-γ levels and a significant decrease in IL-10 and IL-4 levels thus skewing the immune response towards Th1 type. Hence, immunochemotherapy is more effective

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

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    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

  18. Transcriptional Profiling in Experimental Visceral Leishmaniasis Reveals a Broad Splenic Inflammatory Environment that Conditions Macrophages toward a Disease-Promoting Phenotype

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    Spratt, Heidi; Travi, Bruno L.; Luxon, Bruce A.

    2017-01-01

    Visceral Leishmaniasis (VL), caused by the intracellular protozoan Leishmania donovani, is characterized by relentlessly increasing visceral parasite replication, cachexia, massive splenomegaly, pancytopenia and ultimately death. Progressive disease is considered to be due to impaired effector T cell function and/or failure of macrophages to be activated to kill the intracellular parasite. In previous studies, we used the Syrian hamster (Mesocricetus auratus) as a model because it mimics the progressive nature of active human VL. We demonstrated previously that mixed expression of macrophage-activating (IFN-γ) and regulatory (IL-4, IL-10, IL-21) cytokines, parasite-induced expression of macrophage arginase 1 (Arg1), and decreased production of nitric oxide are key immunopathologic factors. Here we examined global changes in gene expression to define the splenic environment and phenotype of splenic macrophages during progressive VL. We used RNA sequencing coupled with de novo transcriptome assembly, because the Syrian hamster does not have a fully sequenced and annotated reference genome. Differentially expressed transcripts identified a highly inflammatory spleen environment with abundant expression of type I and type II interferon response genes. However, high IFN-γ expression was ineffective in directing exclusive M1 macrophage polarization, suppressing M2-associated gene expression, and restraining parasite replication and disease. While many IFN-inducible transcripts were upregulated in the infected spleen, fewer were induced in splenic macrophages in VL. Paradoxically, IFN-γ enhanced parasite growth and induced the counter-regulatory molecules Arg1, Ido1 and Irg1 in splenic macrophages. This was mediated, at least in part, through IFN-γ-induced activation of STAT3 and expression of IL-10, which suggests that splenic macrophages in VL are conditioned to respond to macrophage activation signals with a counter-regulatory response that is ineffective and even

  19. Therapeutic vaccination with recombinant adenovirus reduces splenic parasite burden in experimental visceral leishmaniasis.

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    Maroof, Asher; Brown, Najmeeyah; Smith, Barbara; Hodgkinson, Michael R; Maxwell, Alice; Losch, Florian O; Fritz, Ulrike; Walden, Peter; Lacey, Charles N J; Smith, Deborah F; Aebischer, Toni; Kaye, Paul M

    2012-03-01

    Therapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. Here, we describe the development of an adenovirus-based vaccine (Ad5-KH) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2A sequence. In nonvaccinated Leishmania donovani-infected BALB/c mice, HASPB- and KMP11-specific CD8(+) T cell responses were undetectable, although IgG1 and IgG2a antibodies were evident. After therapeutic vaccination, antibody responses were boosted, and IFNγ(+)CD8(+) T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by ∼66%, a level of efficacy comparable to that observed in early stage testing of clinically approved antileishmanial drugs in this model. These studies indicate the usefulness of adenoviral vectors to deliver leishmanial antigens in a potent and host protective manner to animals with existing L. donovani infection.

  20. Pancreatic involvement in co-infection visceral leishmaniasis and HIV: histological and ultrastructural aspects

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    CHEHTER Ethel Zimberg

    2001-01-01

    Full Text Available The involvement of the gastrointestinal tract in the co-infection of HIV and Leishmania is rarely reported. We report the case of an HIV-infected adult man co-infected with a disseminated form of leishmaniasis involving the liver, lymph nodes, spleen and, as a feature reported for the first time in the English literature, the pancreas. Light microscopy showed amastigote forms of Leishmania in pancreatic macrophages and immunohistochemical staining revealed antigens for Leishmania and also for HIV p24. Microscopic and ultrastructural analysis revealed severe acinar atrophy, decreased zymogen granules in the acinar cytoplasm and also nuclear abnormalities such as pyknosis, hyperchromatism and thickened chromatin. These findings might correspond to the histologic pattern of protein-energy malnutrition in the pancreas as shown in our previous study in pancreas with AIDS and no Leishmania. In this particular case, the protein-energy malnutrition may be due to cirrhosis, or, Leishmania or HIV infection or all mixed. We believe that this case represents the morphologic substratum of the protein energy malnutrition in pancreas induced by the HIV infection. Further studies are needed to elucidate these issues.

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

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    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.

  2. Performance of a rapid diagnostic test for the detection of visceral leishmaniasis in a large urban setting

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    Alexandre Sampaio Moura

    2013-09-01

    Full Text Available Introduction Rapid diagnostic tests (RDTs may improve the early detection of visceral leishmaniasis (VL, but their real-world performance requires additional study. Therefore, we evaluated the performance of an rK39-based RDT (Kalazar Detect™ for the detection of VL in an endemic, large urban area. Methods Data were collected from a registry of rK39 RDT performed at 11 emergency care units in Belo Horizonte, Brazil, and from a national database of reportable communicable diseases of the Sistema de Informação de Agravos de Notificação (SINAN. Results The rapid rK39 test was performed in 476 patients, with 114 (23.9% positive results. The analysis of rK39 RDT performance was based on 381 (80% cases reported to the SINAN database, of which 145 (38.1% were confirmed cases. Estimates for sensitivity and specificity were 72.4% (95% CI: 64.6-79% and 99.6% (95%CI: 97.6-99.9%, respectively. Positive and negative predictive values were estimated at 99.1% (95%CI: 94.9-99.8% and 85.5% (95%CI: 80.8-89.1%, respectively. In addition, close agreement between the rK39 RDT and indirect immunofluorescence was observed. Conclusions In summary, the rK39 RDT showed a high specificity but only moderate sensitivity. In endemic areas for VL, treatment may be considered in cases with clinical manifestations and a positive rK39 RDT, but those with a negative test should be subjected to further investigation.

  3. Molecular Identification and Polymorphism Determination of Cutaneous and Visceral Leishmaniasis Agents Isolated from Human and Animal Hosts in Iran

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    Homa Hajjaran

    2013-01-01

    Full Text Available Amplification of internal transcript spacer 1 of ribosomal RNA (ITS1-RNA gene followed by RFLP analysis and sequencing was used to identify the causing agents of cutaneous and visceral leishmaniasis (CL and VL in humans and animal reservoir hosts from various geographical areas in Iran. We also used random amplified polymorphic DNA (RAPD-PCR to obtain polymorphisms among isolates of Leishmania spp. Totally, 362 suspected human and animal cases including 173 CL, 49 VL, 60 rodents, and 80 domestic dogs were examined for Leishmania infection. From 112 culture-positive samples prepared from CL cases, 75 (67% were infected with L. major and 37 (33% with L. tropica. Of the 60 rodents examined, 25 (41.6% harbored the Leishmania infection; 21 were infected with L. major and 4 with L. turanica. From 49 suspected VL, 29 were positive by direct agglutination test (DAT, whereas microscopy detected parasite in bone marrow of 25 and culture in 28 of the patients. Two VL patients were infected with L. tropica and 26 with L. infantum. Of the 80 domestic dogs, 56 showed anti-Leishmania antibodies with DAT. Of these, 55 were positive by both microscopy and culture. Molecular identity, obtained only for 47 samples, revealed L. infantum in 43 and L. tropica in 4 dogs. The polymorphisms among L. tropica and L. major isolates were 3.6% and 7.3%; the rate among human and canine VL isolates was 2.8% and 9.8%, respectively. Our results showed that at least four different Leishmania species with various polymorphisms circulate among humans and animal hosts in Iran.

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

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    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

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

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    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.

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

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    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.

  7. Eco-epidemiology of visceral leishmaniasis in the urban area of Paracatu, state of Minas Gerais, Brazil.

    Science.gov (United States)

    Dias, Edelberto Santos; Regina-Silva, Shara; França-Silva, João Carlos; Paz, Gustavo Fontes; Michalsky, Erika Monteiro; Araújo, Simone Costa; Valadão, Josiane Lopes; de Oliveira Lara-Silva, Fabiana; de Oliveira, Fernanda Santos; Pacheco, Raquel Silva; Fortes-Dias, Consuelo Latorre

    2011-03-10

    The present study was developed in the urban area of Paracatu, an endemic city for the American visceral leishmaniasis in Brazil. A six-month canine survey was performed with 6295 domiciled dogs in 28 districts in that area and showed that 4.2% of those (267 dogs) were positive for VL by ELISA and IFAT serum assays. Prevalence ratios for canine VL varied between 1.2% and 16.1%, depending on the district under investigation. Fifteen dogs - 80% of which were clinically asymptomatic for VL - were submitted to a more detailed study that comprised direct parasitological examination and Leishmania kDNA amplification of tissue samples as well as two PCR-RFLP methods using myelocultures. Leishmania amastigotes or Leishmania DNA were detected in all dogs but one. The infecting species of Leishmania was identified in about 50% (7/15) of the sample dogs: Leishmania (Leishmania) chagasi in two of them and, unexpectedly, Leishmania (Leishmania) amazonensis in the remaining five. Three months after the end of confiscation and elimination of the VL-seropositive dogs in the 28 districts of Paracatu, a systematic entomological survey was performed in five of them. Six hundred and sixty five (665) phlebotomine sand flies were captured in total, from which 89.5% were identified as Lutzomyia longipalpis. The population density of that species increased during the rainy season. Other thirteen (13) species of phlebotomine sand flies were captured at varying percentages from 0.2 to 5.0%. It is worth noting that L. longipalpis females were predominantely intradomicile when compared to males, suggesting that the VL transmission cycle in Paracatu may be occurring inside home.

  8. Evaluation of the immunoprophylactic potential of a killed vaccine candidate in combination with different adjuvants against murine visceral leishmaniasis.

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    Thakur, Ankita; Kaur, Harpreet; Kaur, Sukhbir

    2015-02-01

    Despite a large number of field trials, till date no prophylactic antileishmanial vaccine exists for human use. Killed antigen formulations offer the advantage of being safe but they have limited immunogenicity. Recent research has documented that efforts to develop effective Leishmania vaccine have been limited due to the lack of an appropriate adjuvant. Addition of adjuvants to vaccines boosts and directs the immunogenicity of antigens. So, the present study was done to evaluate the effectiveness of four adjuvants i.e. alum, saponin, cationic liposomes and monophosphoryl lipid-A in combination with Autoclaved Leishmania donovani (ALD) antigen against murine visceral leishmaniasis (VL). BALB/c mice were immunized thrice with respective vaccine formulation. Two weeks after last booster, challenge infection was given. Mice were sacrificed 15 days after last immunization and on 30, 60 and 90 post infection/challenge days. A considerable protective efficacy was shown by all vaccine formulations. It was evident from significant reduction in parasite load, profound delayed type hypersensitivity responses (DTH), increased IgG2a titres and high levels of Th1 cytokines (IFN-γ, IL-12) as compared to the infected controls. However, level of protection varied with the type of adjuvant used. Maximum protection was achieved with the use of liposome encapsulated ALD antigen and it was closely followed by group immunized with ALD+MPL-A. Significant results were also obtained with ALD+saponin, ALD+alum and ALD antigen (alone) but the protective efficacy was reduced as compared to other immunized groups. The present study reveals greater efficacy of two vaccine formulations i.e. ALD+liposome and ALD+MPL-A against murine VL.

  9. The genetic structure of Leishmania infantum populations in Brazil and its possible association with the transmission cycle of visceral leishmaniasis.

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    Gabriel Eduardo Melim Ferreira

    Full Text Available Leishmania infantum is the etiologic agent of visceral leishmaniasis (VL in the Americas, Mediterranean basin and West and Central Asia. Although the geographic structure of L. infantum populations from the Old World have been described, few studies have addressed the population structure of this parasite in the Neotropical region. We employed 14 microsatellites to analyze the population structure of the L. infantum strains isolated from humans and dogs from most of the Brazilian states endemic for VL and from Paraguay. The results indicate a low genetic diversity, high inbreeding estimates and a depletion of heterozygotes, which together indicate a predominantly clonal breeding system, but signs of sexual events are also present. Three populations were identified from the clustering analysis, and they were well supported by F statistics inferences and partially corroborated by distance-based. POP1 (111 strains was observed in all but one endemic area. POP2 (31 strains is also well-dispersed, but it was the predominant population in Mato Grosso (MT. POP3 (31 strains was less dispersed, and it was observed primarily in Mato Grosso do Sul (MS. Strains originated from an outbreak of canine VL in Southern Brazil were grouped in POP1 with those from Paraguay, which corroborates the hypothesis of dispersal from Northeastern Argentina and Paraguay. The distribution of VL in MS seems to follow the west-east construction of the Bolivia-Brazil pipeline from Corumbá municipality. This may have resulted in a strong association of POP3 and Lutzomyia cruzi, which is the main VL vector in Corumbá, and a dispersion of this population in this region that was shaped by human interference. This vector also occurs in MT and may influence the structure of POP2. This paper presents significant advances in the understanding of the population structure of L. infantum in Brazil and its association with eco-epidemiological aspects of VL.

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

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    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)

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

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    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.

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

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    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

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

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    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. Do Size and Insecticide Treatment Matter? Evaluation of Different Nets against Phlebotomus argentipes, the Vector of Visceral Leishmaniasis in Nepal.

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    Murari Lal Das

    Full Text Available In the Indian subcontinent, Leishmania donovani, the parasite causing visceral leishmaniasis (VL is transmitted by the sand fly vector Phlebotomus argentipes. Long lasting insecticide treated nets (LN have been postulated as alternative or complement to Indoor Residual Spraying but there are few field studies evaluating the entomological efficacy of different nets against this vector. We conducted two crossover trials in a VL endemic area in Nepal to compare the barrier effect of (1 LN with different mesh sizes (156 holes/inch2 vs 625 holes/inch2 and (2 alpha-cypermethrin treated LN and untreated nets having the same mesh size (156 holes/inch2. Each crossover trial had two arms consisting of a sequence of two different nets for 8 nights. We used 10 cattle sheds per trial. A cow placed under the net was used as bait. CDC light traps placed inside the nets were used to evaluate the number of P. argentipes crossing the net barrier. Negative binomial generalized estimating equation (GEE population-averaged models adjusted by night and sequence were used to estimate the barrier effect of the different nets. The crossover trials conducted in a rural village in Morang district (South-eastern Nepal demonstrated that reducing the size of the holes in treated nets (625 holes/inch2 increased the barrier effect of LN by 77% (95% confidence interval (CI: 56%-88% compared with treated nets with larger holes (156 holes/inch2. Treating nets with alpha-cypermethrin reduced the number of P. argentipes captured inside the nets by 77% (95% CI: 27%-93% compared with untreated nets. The effectiveness and acceptability of finer mesh pyrethroid treated LN should be tested for VL prevention in a randomized controlled trial.

  15. Infrared fluorescent imaging as a potent tool for in vitro, ex vivo and in vivo models of visceral leishmaniasis.

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    Estefanía Calvo-Álvarez

    2015-03-01

    Full Text Available Visceral leishmaniasis (VL is hypoendemic in the Mediterranean region, where it is caused by the protozoan Leishmania infantum. An effective vaccine for humans is not yet available and the severe side-effects of the drugs in clinical use, linked to the parenteral administration route of most of them, are significant concerns of the current leishmanicidal medicines. New drugs are desperately needed to treat VL and phenotype-based High Throughput Screenings (HTS appear to be suitable to achieve this goal in the coming years.We generated two infrared fluorescent L. infantum strains, which stably overexpress the IFP 1.4 and iRFP reporter genes and performed comparative studies of their biophotonic properties at both promastigote and amastigote stages. To improve the fluorescence emission of the selected reporter in intracellular amastigotes, we engineered distinct constructs by introducing regulatory sequences of differentially-expressed genes (A2, AMASTIN and HSP70 II. The final strain that carries the iRFP gene under the control of the L. infantum HSP70 II downstream region (DSR, was employed to perform a phenotypic screening of a collection of small molecules by using ex vivo splenocytes from infrared-infected BALB/c mice. In order to further investigate the usefulness of this infrared strain, we monitored an in vivo infection by imaging BALB/c mice in a time-course study of 20 weeks.The near-infrared fluorescent L. infantum strain represents an important step forward in bioimaging research of VL, providing a robust model of phenotypic screening suitable for HTS of small molecule collections in the mammalian parasite stage. Additionally, HSP70 II+L. infantum strain permitted for the first time to monitor an in vivo infection of VL. This finding accelerates the possibility of testing new drugs in preclinical in vivo studies, thus supporting the urgent and challenging drug discovery program against this parasitic disease.

  16. Clinical forms of canine visceral Leishmaniasis in naturally Leishmania infantum-infected dogs and related myelogram and hemogram changes.

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    Roney de Carvalho Nicolato

    Full Text Available 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.

  17. Associação da carga parasitária renal com achados laboratoriais em cães com leishmaniose visceral Renal parasite load association with laboratory findings in dogs with visceral Leishmaniasis

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    Mariana de Medeiros Torres

    2013-05-01

    Full Text Available A leishmaniose visceral canina é uma doença grave e a morte ocorre por falência renal, considerando que os métodos diagnósticos convencionais não possibilitam a classificação clínica do animal. O objetivo deste estudo foi associar a carga parasitária renal aos achados clínicos e histopatológicos em cães com leishmaniose visceral. A análise microscópica revelou predomínio de nefrite intersticial mononuclear de graus variados em 59,3% dos cães avaliados. Entretanto, não houve diferença entre a carga parasitária renal de sintomáticos e oligossintomáticos (P= 0,35. As lesões renais foram de ordem inflamatória e a quantidade de parasitos não influenciaram na característica dessas lesões e nem nas alterações bioquímicas, mesmo em cães com diferentes classificações clínicas.Canine visceral leishmaniasis is a severe disease and the death occurs from renal failure, whereas conventional diagnostic methods do not allow the animal clinical staging. The aim of this study was to associate the renal parasite load to clinical and histopathological findings in dogs with visceral Leishmaniasis. Microscopic analysis revealed a predominance of mononuclear interstitial nephritis of varying degrees in 59, 3% of dogs evaluated. However, no difference was found between the renal parasite load of symptomatics and oligosymptomatics (P= 0,35. Renal lesions were inflammatory order and amount of parasites not influenced the characteristics of theses lesions nor biochemical changes, even in dogs with different clinical classifications.

  18. Five-Year Field Results and Long-Term Effectiveness of 20 mg/kg Liposomal Amphotericin B (Ambisome) for Visceral Leishmaniasis in Bihar, India

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    Sakib Burza; Sinha, Prabhat K.; Raman Mahajan; María Angeles Lima; Gaurab Mitra; Neena Verma; Manica Balasegaram; Pradeep Das

    2014-01-01

    BACKGROUND: Visceral Leishmaniasis (VL; also known as Kala-azar) is an ultimately fatal disease endemic in Bihar. A 2007 observational cohort study in Bihar of 251 patients with VL treated with 20 mg/Kg intravenous liposomal amphotericin B (Ambisome) demonstrated a 98% cure rate at 6-months. Between July 2007 and August 2012, Médecins Sans Frontières (MSF) and the Rajendra Memorial Research Institute (RMRI) implemented a VL treatment project in Bihar, India-an area highly endemic for Leishman...

  19. Splenic CD4+ T Cells in Progressive Visceral Leishmaniasis Show a Mixed Effector-Regulatory Phenotype and Impair Macrophage Effector Function through Inhibitory Receptor Expression

    Science.gov (United States)

    Osorio, Elvia Y.; Saldarriaga, Omar A.; Travi, Bruno L.; Kong, Fanping; Spratt, Heidi; Soong, Lynn

    2017-01-01

    Visceral leishmaniasis (VL), caused by infection with the intracellular protozoan Leishmania donovani, is a chronic progressive disease with a relentlessly increasing parasite burden in the spleen, liver and bone marrow. The disease is characterized by fever, splenomegaly, cachexia, and pancytopenia, and progresses to death if not treated. Control of Leishmania infection is mediated by Th1 (IFNγ-producing) CD4+ T cells, which activate macrophages to produce nitric oxide and kill intracellular parasites. However, despite expansion of CD4+ T cells and increased IFNγ expression in the spleen, humans with active VL do not control the infection. We used an experimental model of chronic progressive VL in hamsters, which mimics clinical and pathological features seen in humans, to better understand the mechanisms that lead to progressive disease. Transcriptional profiling of the spleen during chronic infection revealed expression of markers of both T cell activation and inhibition. CD4+ T cells isolated from the spleen during chronic progressive VL showed mixed expression of Th1 and Th2 cytokines and chemokines, and were marginally effective in controlling infection in an ex vivo T cell-macrophage co-culture system. Splenic CD4+ T cells and macrophages from hamsters with VL showed increased expression of inhibitory receptors and their ligands, respectively. Blockade of the inhibitory receptor PD-L2 led to a significant decrease in parasite burden, revealing a pathogenic role for the PD-1 pathway in chronic VL. PD-L2 blockade was associated with a dramatic reduction in expression of host arginase 1, but no change in IFNγ and inducible nitric oxide synthase. Thus, the expression of counter-regulatory molecules on splenic CD4+ T cells and macrophages promotes a more permissive macrophage phenotype and attenuates intracellular parasite control in chronic progressive VL. Host-directed adjunctive therapy targeting the PD-1 regulatory pathway may be efficacious for VL. PMID

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

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    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

  1. Treatment of visceral leishmaniasis with intravenous pentamidine and oral fluconazole in an HIV-positive patient with chronic renal failure--a case report and brief review of the literature.

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    Rybniker, Jan; Goede, Valentin; Mertens, Jessica; Ortmann, Monika; Kulas, Wolfgang; Kochanek, Matthias; Benzing, Thomas; Arribas, José R; Fätkenheuer, Gerd

    2010-06-01

    We report the case of an HIV-positive patient with visceral leishmaniasis and several relapses after treatment with the two first-line anti-leishmanial drugs, liposomal amphotericin B and miltefosine. End-stage renal failure occurred in 2007 when the patient was on long-term treatment with miltefosine. A relapse of leishmaniasis in 2008 was successfully treated with a novel combination regimen of intravenous pentamidine and oral fluconazole. Secondary prophylaxis with fluconazole monotherapy did not prevent parasitological relapse of leishmaniasis.

  2. Noninvasive Diagnosis of Visceral Leishmaniasis: Development and Evaluation of Two Urine-Based Immunoassays for Detection of Leishmania donovani Infection in India

    Science.gov (United States)

    Ejazi, Sarfaraz Ahmad; Bhattacharya, Pradyot; Bakhteyar, Md. Asjad Karim; Mumtaz, Aquil Ahmad; Pandey, Krishna; Das, Vidya Nand Ravi; Das, Pradeep; Rahaman, Mehebubar; Goswami, Rama Prosad; Ali, Nahid

    2016-01-01

    Background Visceral Leishmaniasis (VL), a severe parasitic disease, could be fatal if diagnosis and treatment is delayed. Post kala-azar dermal leishmaniasis (PKDL), a skin related outcome, is a potential reservoir for the spread of VL. Diagnostic tests available for VL such as tissue aspiration are invasive and painful although they are capable of evaluating the treatment response. Serological tests although less invasive than tissue aspiration are incompetent to assess cure. Parasitological examination of slit-skin smear along with the clinical symptoms is routinely used for diagnosis of PKDL. Therefore, a noninvasive test with acceptable sensitivity and competency, additionally, to decide cure would be an asset in disease management and control. Methodology/principal findings We describe here, the development of antibody-capture ELISA and field adaptable dipstick test as noninvasive diagnostic tools for VL and PKDL and as a test of cure in VL treatment. Sensitivity and specificity of urine-ELISA were 97.94% (95/97) and 100% (75/75) respectively, for VL. Importantly, dipstick test demonstrated 100% sensitivity (97/97) and specificity (75/75) in VL diagnosis. Degree of agreement of the two methods with tissue aspiration was 98.83% (κ = 0.97) and 100% (κ = 1), for ELISA and dipstick test, respectively. Both the tests had 100% positivity for PKDL (14/14) cases. ELISA and dipstick test illustrated treatment efficacy in about 90% (16/18) VL cases when eventually turned negative after six months of treatment. Conclusions/significance ELISA and dipstick test found immensely effective for diagnosis of VL and PKDL through urine samples thus, may substitute the existing invasive diagnostics. Utility of these tests as indirect methods of monitoring parasite clearance can define infected versus cured. Urine-based dipstick test is simple, sensitive and above all noninvasive method that may help not only in active VL case detection but also to ascertain treatment response

  3. Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral leishmaniasis.

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    Renata A O Castro

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum. METHODOLOGY/PRINCIPAL FINDINGS: Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII, in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues. CONCLUSIONS/SIGNIFICANCE: Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to

  4. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.

    Science.gov (United States)

    Perry, Meghan R; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H

    2013-12-03

    The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg · mL(-1) Pentostam compared with the control passage group (38.5 μg · mL(-1)) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  6. Profile and geographic distribution of reported cases of visceral leishmaniasis in Campo Grande, State of Mato Grosso do Sul, Brazil, from 2002 to 2009

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    Júlia Cristina Maksoud Brazuna

    2012-10-01

    Full Text Available INTRODUCTION: This study sought to describe the profile and geographic distribution of reported cases of visceral leishmaniasis (VL in the City of Campo Grande, State of Mato Grosso do Sul (MS, Brazil, from 2002 to 2009. METHODS: Human data were collected from the Brazilian National Information System for Notifiable Diseases. Canine cases and entomological data were obtained from the Information Service for Canine Visceral Leishmaniasis Control/Campo Grande, MS. RESULTS: A total of 951 records from 2002 to 2009 were investigated. The number of reported cases of VL in males was significantly higher (p < 0.0001 than that in females. The higher frequency observed among males was associated with age (p < 0.0001, which increased in individuals aged 40 years and older. The overall fatality rate was 7.4%. Entomological surveys conducted in 2006, 2007, and 2009 showed the insect vector Lutzomyia longipalpis to be present in all urban regions of the county. CONCLUSIONS: VL cases in humans and dogs, as well as in vectors, occurs in all urban regions of Campo Grande. Despite not observing tendencies of increase or reduction in the incidence of the disease due to aging, the major incidence in men is higher in those aged 40 years or above.

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

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    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.

  8. Prevalence, features and risk factors for malaria co-infections amongst visceral leishmaniasis patients from Amudat Hospital, Uganda.

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    Erika van den Bogaart

    Full Text Available BACKGROUND AND METHODOLOGY: Due to geographic overlap of malaria and visceral leishmaniasis (VL, co-infections may exist but have been poorly investigated. To describe prevalence, features and risk factors for VL-malaria co-infections, a case-control analysis was conducted on data collected at Amudat Hospital, Uganda (2000-2006 by Médecins sans Frontières. Cases were identified as patients with laboratory-confirmed VL and malaria at hospital admission or during hospitalization; controls were VL patients with negative malaria smears. A logistic regression analysis was performed to study the association between patients' characteristics and the occurrence of the co-infection. RESULTS: Of 2414 patients with confirmed VL, 450 (19% were positively diagnosed with concomitant malaria. Most co-infected patients were males, residing in Kenya (69%. While young age was identified by multivariate analysis as a risk factor for concurrent VL and malaria, particularly the age groups 0-4 (odds ratio (OR: 2.44; 95% confidence interval (CI: 1.52-3.92 and 5-9 years (OR: 2.23, 95% CI: 1.45-3-45, mild (OR: 0.53; 95% CI: 0.32-0.88 and moderate (OR: 0.45; 95% CI: 0.27-0.77 anemia negatively correlated with the co-morbidity. VL patients harboring skin infections were nearly three times less likely to have the co-infection (OR: 0.35; 95% CI: 0.17-0.72, as highlighted by the multivariate model. Anorexia was slightly more frequent among co-infected patients (OR: 1.71; 95% CI: 0.96-3.03. The in-hospital case-fatality rate did not significantly differ between cases and controls, being 2.7% and 3.1% respectively (OR: 0.87; 95% CI: 0.46-1.63. CONCLUSIONS: Concurrent malaria represents a common condition among young VL patients living in the Pokot region of Kenya and Uganda. Although these co-morbidities did not result in a poorer prognosis, possibly due to early detection of malaria, a positive trend towards more severe symptoms was identified, indicating that routine

  9. Mortality and case fatality due to visceral leishmaniasis in Brazil: a nationwide analysis of epidemiology, trends and spatial patterns.

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    Francisco Rogerlândio Martins-Melo

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a significant public health problem in Brazil and several regions of the world. This study investigated the magnitude, temporal trends and spatial distribution of mortality related to VL in Brazil. METHODS: We performed a study based on secondary data obtained from the Brazilian Mortality Information System. We included all deaths in Brazil from 2000 to 2011, in which VL was recorded as cause of death. We present epidemiological characteristics, trend analysis of mortality and case fatality rates by joinpoint regression models, and spatial analysis using municipalities as geographical units of analysis. RESULTS: In the study period, 12,491,280 deaths were recorded in Brazil. VL was mentioned in 3,322 (0.03% deaths. Average annual age-adjusted mortality rate was 0.15 deaths per 100,000 inhabitants and case fatality rate 8.1%. Highest mortality rates were observed in males (0.19 deaths/100,000 inhabitants, <1 year-olds (1.03 deaths/100,000 inhabitants and residents in Northeast region (0.30 deaths/100,000 inhabitants. Highest case fatality rates were observed in males (8.8%, ≥ 70 year-olds (43.8% and residents in South region (17.7%. Mortality and case fatality rates showed a significant increase in Brazil over the period, with different patterns between regions: increasing mortality rates in the North (Annual Percent Change--APC: 9.4%; 95% confidence interval--CI: 5.3 to 13.6, and Southeast (APC: 8.1%; 95% CI: 2.6 to 13.9; and increasing case fatality rates in the Northeast (APC: 4.0%; 95% CI: 0.8 to 7.4. Spatial analysis identified a major cluster of high mortality encompassing a wide geographic range in North and Northeast Brazil. CONCLUSIONS: Despite ongoing control strategies, mortality related to VL in Brazil is increasing. Mortality and case fatality vary considerably between regions, and surveillance and control measures should be prioritized in high-risk clusters. Early diagnosis and treatment

  10. Comparative evaluation of the DPP(®) CVL rapid test for canine serodiagnosis in area of visceral leishmaniasis.

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    Laurenti, M D; de Santana Leandro, M V; Tomokane, T Y; De Lucca, H R L; Aschar, M; Souza, C S F; Silva, R M; Marcondes, M; da Matta, V L R

    2014-10-15

    We investigated the performance of the DPP(®) canine visceral leishmaniasis (CVL) rapid test, a novel immunochromatographic assay launched by BioManguinhos (Brazil), which was recently included in the new Brazilian protocol for screening CVL in serological surveys. The present study compared the DPP(®) with the ELISA and IFA produced by BioManguinhos (Brazil) both with L. major-like antigens and with in-house tests using Leishmania infantum chagasi (in-house ELISA and in-house IFA). We analyzed the sera from clinically symptomatic (n=47) and asymptomatic (n=38) infected dogs from an endemic area of CVL, as well as from healthy (n=18) dogs, in addition to the sera of dogs (n=81) infected with other pathogens. The DPP(®) and the in-house ELISA showed a sensitivity of 90.6% and 94.1%, respectively, and specificity of 95.1% and 97.5%, respectively, and both presented cross-reactivity only with the sera of dogs with babesiosis, 44% for the DPP(®) and 22% for the in-house ELISA. The clinical groups were detected equally by the two assays. The ELISA BioManguinhos, IFA BioManguinhos, and in house-IFA showed a good sensitivity, 90.6%, 96.5% and 89.4%, respectively, but very low specificity, 77.8%, 69.1% and 65.8%, respectively, due to the high cross-reactivity with the sera from the animals harboring other pathogens. The in-house ELISA provided the highest accuracy (95.8%), followed by the DPP(®) (92.7%), ELISA BioManguinhos (84.3%), IFA BioManguinhos (83.1%), and in-house IFA (78.0%). The simultaneous use of the DPP(®) and ELISA BioManguinhos reached a sensitivity of 99.1% and 82.1% when used sequentially. In conclusion, the DPP(®) performed well as serological test for CVL, and detected both asymptomatic and symptomatic dogs in equal proportions. Although its sensitivity is not ideal yet, discarding the IFA and including the DPP(®) improved the accuracy of the new Brazilian CVL diagnostic protocol, particularly of detecting truly infected dogs. Moreover

  11. Efficacy of anti-leishmania therapy in visceral leishmaniasis among HIV infected patients: a systematic review with indirect comparison.

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    Gláucia F Cota

    Full Text Available OBJECTIVE: We conducted a systematic literature review with indirect comparison of studies evaluating therapeutic efficacy and toxicity associated to visceral leishmaniasis (VL therapy among HIV infected individuals. MAIN OUTCOME MEASUREMENTS: The outcomes of interest were clinical and parasitological cure, mortality, and adverse events. METHODS: PRISMA guidelines for systematic reviews and Cochrane manual were followed. Sources were MEDLINE, LILACS, EMBASE, Web of Knowledge databases and manual search of references from evaluated studies. We included all studies reporting outcomes after VL treatment, regardless of their design. Study quality was evaluated systematically by using the Newcastle-Ottawa Scale (NOS for assessing the quality of nonrandomized studies in meta-analyses. Comprehensive Meta-Analysis software v.2.2.048 was used to perform one-group meta-analysis of study arms with the same drug to estimate global rates of success and adverse events with each drug. These estimates were used, when possible, to indirectly compare treatment options, adjusted for CD4 count. Direct comparison was pooled when available. RESULTS: Seventeen studies reporting five treatment regimens and outcome of 920 VL episodes occurring in HIV infected individuals were included. The main outstanding difference in outcome among the treatment regimens was observed in mortality rate: it was around 3 times higher with high-dose antimony use (18.4%, CI 95% 13.3-25%, indirectly compared to lipid formulations of amphotericin B treatment (6.1%, CI 95% 3.9-9.4%. It was observed, also by indirect comparison, higher rates of clinical improvement in study arms using amphotericin B than in study arms using pentavalent antimonial therapy (Sb(v. The parasitological cure, an outcome that presented some degree of risk of selection and verification bias, had rates that varied widely within the same treatment arm, with high heterogeneity, hampering any formal comparison among drugs

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

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    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.

  13. Understanding the transmission dynamics of Leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in Bihar, India the LCNTDR Collection: Advances in scientific research for NTD control

    NARCIS (Netherlands)

    M.M. Cameron (Mary M.); A. Acosta-Serrano (Alvaro); C. Bern (Caryn); M. Boelaert (Marleen); M. Den Boer (Margriet); S. Burza (Sakib); L.A.C. Chapman (Lloyd A. C.); A. Chaskopoulou (Alexandra); M. Coleman (Michael); O. Courtenay (Orin); S. Croft (Simon); P.K. Das (P.); E. Dilger (Erin); G. Foster (Geraldine); R. Garlapati (Rajesh); L. Haines (Lee); A. Harris (Angela); J. Hemingway (Janet); T.D. Hollingsworth (T. Déirdre); S. Jervis (Sarah); G.F. Medley (Graham F.); M. Miles (Michael); M. Paine (Mark); A. Picado (Albert); R. Poché (Richard); P. Ready (Paul); M. Rogers (Matthew); M. Rowland (Mark); S. Sundar (Shyam); S.J. de Vlas (Sake); D. Weetman (David)

    2016-01-01

    textabstractVisceral Leishmaniasis (VL) is a neglected vector-borne disease. In India, it is transmitted to humans by Leishmania donovani-infected Phlebotomus argentipes sand flies. In 2005, VL was targeted for elimination by the governments of India, Nepal and Bangladesh by 2015. The elimination st

  14. Safety and Efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Omollo, R.; Alexander, N.; Edwards, T.; Khalil, E.A.G.; Younis, B.M.; Abuzaid, A.A.; Wasunna, M.; Njoroge, N.; Kinoti, D.; Kirigi, G.; Dorlo, T.P.C.; Ellis, S.; Balasegaram, M.; Musa, A.M.

    2011-01-01

    BACKGROUND: Treatment options for Visceral Leishmaniasis (VL) in East Africa are far from satisfactory due to cost, toxicity, prolonged treatment duration or emergence of parasite resistance. Hence there is a need to explore alternative treatment protocols such as miltefosine alone or in combination

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

    Institute of Scientific and Technical Information of China (English)

    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.

  16. 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

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    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

  17. Bone marrow leishmaniasis: a review of situation in Thailand.

    Science.gov (United States)

    Wiwanitkit, Viroj

    2011-10-01

    Leishmaniasis is an important tropical vector-borne disease. This infection can be seen in tropical area and it is considered to be one of the most important vector-borne infections at present. The general situation of the leishmaniasis in Thailand is hereby reviewed. Although Thailand is a tropical country, the leishmaniasis is not endemic but sporadic. The imported cases are documented in some literatures. The serious form of leishmaniasis, the visceral leishmaniasis is also detectable in Thailand. Also, the author performed an in depth literature review of the reports of bone marrow leishmaniasis, a specific kind of visceral leishmaniasis, in Thailand in order to summarize the characteristics of this infection among Thai patients. According to this review, there have been at least 5 reports in the literature of 6 cases of bone marrow leishmaniasis in the Thai population, of which no case was lethal. Concerning the clinical manifestations, all except had prolonged fever with unknown origin. From physical examination, all had hepatosplenomegaly. The striking findings were active hemophagocytosis with increased proliferation of lymphoidplasma cell line in the bone marrow and amastigotes of Leishmania donovani was demonstrated. Considering the treatment, pantavalent antimony compound was used and the excellent improvement and complete recovery. Finally, the author also discussed on the importance of leishmaniasis in Thailand relating to the present globalization and good traveling system.

  18. Travelers' Health: Leishmaniasis, Visceral

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    ... in an Area with Zika? Find a Clinic Yellow Fever Vaccinations Clinics FAQ Disease Directory Resources Resources for ... CE Courses and Training Presentations for Health Professionals Yellow Fever Vaccine Course About the Yellow Fever Vaccine Course ...

  19. Leishmania donovani: assessment of leishmanicidal effects of herbal extracts obtained from plants in the visceral leishmaniasis endemic area of Bihar, India.

    Science.gov (United States)

    Singh, Shubhankar K; Bimal, Sanjiva; Narayan, Shyam; Jee, Chandrawati; Bimal, Devla; Das, P; Bimal, Raageeva

    2011-02-01

    One obstacle faced in the effective control of visceral leishmaniasis (VL) is the limited number of available treatment options. Furthermore, control efforts have been hindered further by the emergence of Leishmania resistance to many of the available drugs. In this study, we investigated the anti-leishmanial properties of 30 medicinally important plants from the VL endemic area of Bihar, India and compared them to two available anti-leishmanial drugs (sodium antimony gluconate and amphotericin B) and two plant lectins (phytohemagglutinin and concanavalin A) on Leishmania donovani promastigotes in vitro at 24 and 48 h after initiation of culture. We identified eight plant extracts in addition to phytohemagglutinin and amphotericin B that significantly inhibited the growth of promastigotes (p Agave americana, Azadirachta indica, Eclipta alba and Piper longum) of the eight plant extracts that induced significant promastigotes killing (p = 0.00098). Effect-based dose finding analysis revealed that the threshold concentration of A. americana required to eliminate L. donovani after 24h was 0.05 mg/ml. A. indica and P. longum plant extracts eliminated L. donovani promastigotes after 48 h at concentrations of 0.1 and 0.5mg/ml, respectively. E. alba eliminated the promastigotes at a concentration of 0.5mg/ml within 24h. The axenic amastigote killing response was 1.90-, 2.52- and 1.3-fold higher than the promastigote killing response with A. indica, A. americana and E. alba plant extracts, respectively. A. americana and A. indica, respectively, led to approximate 2.5- and 1.3-fold declines in mitochondrial dehydrogenase activity compared with control. E. alba stimulation resulted in an up-regulation of dehydrogenase activity (p = 0.00329). The CSA from P. longum was found to be least cytotoxic; the observed difference in mitochondrial activity was insignificant (p = 0.16314). Further studies may reveal the pharmacological significance of many of the plants with anti

  20. Visceral leishmaniasis elimination programme in India, Bangladesh, and Nepal: reshaping the case finding/case management strategy.

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    Dinesh Mondal

    Full Text Available OBJECTIVE: We sought to estimate visceral leishmaniasis (VL burden in Bangladesh, India, and Nepal and document care-seeking behaviour for VL to provide baseline information for monitoring the VL elimination program and identify options for improved case finding and management. DESIGN: A cross-sectional study using cluster sampling (clusters being villages of 4 VL endemic districts was used in order to document all current and existing VL cases over the preceding 12 mo. Extended (in-depth interviews were conducted in a subsample of households to explore (a VL-related knowledge, attitudes, and practices of the population; (b use of VL care by patients; and (c delay between onset of symptoms, diagnosis, and start of treatment, as well as treatment interruption. Findings were discussed with national program managers and policy makers to develop improved strategies. RESULTS: Screening for VL was done in 18,933 households (106,425 inhabitants. The estimated annual incidence of VL in the endemic districts was on average 22 times higher than the elimination target of less than one case per 10,000 inhabitants in 2015. This incidence varied widely between study sites, from 9.0 to 29.8 per 10,000 inhabitants. The percentage of newly detected cases through the household screening was high in the districts least covered by health-care services (particularly Rajshahi, Bangladesh, 49%; and to a lesser extent Vaishali in Bihar, India, 32.5%, and much lower in districts with greater availability of VL care (Muzaffarpur, India, 3.8%. On average 267 houses had to be visited, i.e., at least three to four working days per health worker, to identify a new VL (ranging from 1,432 houses in Muzaffarpur, India to only 166 houses in Rajshahi, Bangladesh. Knowledge of the disease and its vectors was good in India and Nepal but poor in Bangladesh (Rajshahi where very little attention has been given to VL over the last decades. Although all socio-demographic indicators

  1. 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

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    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.

  2. Lutzomyia longipalpis naturally infected by Leishmania (L.) chagasi in Várzea Grande, Mato Grosso State, Brazil, an area of intense transmission of visceral leishmaniasis.

    Science.gov (United States)

    Missawa, Nanci A; Michalsky, Erika Monteiro; Fortes-Dias, Consuelo Latorre; Santos Dias, Edelberto

    2010-12-01

    The American visceral leishmaniasis (AVL) is caused by parasites belonging to the genus Leishmania (Trypanosomatidae) and is transmitted to humans through the bite of certain species of infected phlebotomine sand flies. In this study, we investigated the natural infection ratio of Lutzomyia longipalpis, the main vector species of AVL in Brazil, in Várzea Grande, Mato Grosso State. Between July 2004 and June 2006, phlebotomine sand flies were captured in peridomestic areas using CDC light-traps. Four hundred and twenty (420) specimens of Lu. longipalpis were captured. 42 pools, containing 10 specimens of Lu. longipalpis each, were used for genomic DNA extraction and PCR (polymerase chain reaction) amplification. Leishmania spp. DNA was detected in three out of the 42 pools tested, resulting in a minimal infection ratio of 0.71%. Restriction fragment length polymorphism (RFLP) analysis indicated that Leishmania (L.) chagasi was the infective agent in the positive pools.

  3. Assessment of sand fly (Diptera, Psychodidae) control using cypermethrin in an endemic area for visceral leishmaniasis, Montes Claros, Minas Gerais State, Brazil.

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    Barata, Ricardo Andrade; Michalsky, Erika Monteiro; Fujiwara, Ricardo Toshio; França-Silva, João Carlos; Rocha, Marília Fonseca; Dias, Edelberto Santos

    2011-11-01

    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.

  4. 1例黑热病患儿的循证诊断和治疗%Evidence-based diagnosis and treatment for a child with visceral leishmaniasis

    Institute of Scientific and Technical Information of China (English)

    刘路琼; 董湘玉; 田金徽; 杨克虎

    2012-01-01

    Objective To diagnose quickly and make an individualized therapeutic regimen for a child suspected visceral leishmaniasis by the evidence-based method. Methods Combining with clinical problems of the child and according to PICO (patient, intervention, comparison and outcome) principle, relavent literatures which were searched from official website of China' s Center for Disease Control and Prevention, Cochrane Library, PubMed, Embase and CBM were collected and studied. Then, regime of diagnosis and treatment were defined taking into consideration of parents' intention and clinical experience. Results Evidence shows that the diagnostic performance of rK39 immunochromatography (rK39 ICT) for visceral leishmaniasis is excellent. In China, sodium stibogluconate (SSG) is still the first-line drug used for patients with visceral leishmaniasis. rK39 ICT and bone marrow cytology were taken to diagnose visceral leishmaniasis after informed consent got from parents, then the child was given SSG. Evident improvement of symptoms was achieved without adverse events of SSG and amastigotes of Leishmania donouani was not found by reexamination of bone marrow cytology. Conclusions Evidence-based clinical practice can solve clinical problems quickly and accurately.%目的 借助循证医学方法明确诊断疑似黑热病患儿并拟定治疗方案.方法 针对1例患儿临床问题,遵循循证临床实践的PICO原则(患者或问题、干预措施、对照干预措施及结局指标),检索中华人民共和国卫生部和中国疾病控制中心官网,Cochrane Library,PubMed,Embase和CBM,收集和评价文献以取得当前最佳证据,并结合临床经验及患儿家属的意愿,拟定诊断及治疗方案.结果 经循证分析,rK39免疫层析(rK39 ICT)诊断黑热病的检验效能高,快速、简单;葡萄糖酸锑钠仍可作为黑热病患者治疗的一线药物.在获得家属知情同意后,采用rK39 ICT和骨髓细胞学检查,快速明确诊断后给予葡萄

  5. A novel recombinant Leishmania donovani p45, a partial coding region of methionine aminopeptidase, generates protective immunity by inducing a Th1 stimulatory response against experimental visceral leishmaniasis.

    Science.gov (United States)

    Gupta, Reema; Kushawaha, Pramod K; Tripathi, Chandra Dev Pati; Sundar, Shyam; Dube, Anuradha

    2012-05-01

    The development of a vaccine against visceral leishmaniasis (VL) conferring long-lasting immunity remains a challenge. Identification and proteomic characterization of parasite proteins led to the detection of p45, a member of the methionine aminopeptidase family. To our knowledge the present study is the first known report that describes the molecular and immunological characterization of p45. Recombinant Leishmania donovani p45 (rLdp45) induced cellular responses in cured hamsters and generated Th1-type cytokines from peripheral blood mononuclear cells of cured/endemic VL patients. Immunization with rLdp45 exerted considerable prophylactic efficacy (∼85%) supported by an increase in mRNA expression of iNOS, IFN-γ, TNF-α and IL-12 and decrease in TGF-β and IL-4, indicating its potential as a vaccine candidate against VL.

  6. 新疆喀什地区再度流行内脏利什曼病%Reemergence of visceral leishmaniasis in Kashi Prefecture,Xinjiang

    Institute of Scientific and Technical Information of China (English)

    管立人; 左新平; 依马木

    2003-01-01

    @@ 喀什地区位于新疆南部边陲,辖12县、市.早在20世纪30年代,该地即有内脏利什曼病(visceral leishmaniasis,VL)的报道,50年代初确定当地为VL疫区,70年代中期在疏附三角洲(喀什、疏附和疏勒三县市)VL曾一度流行,年发病人数在200例左右,经1977~1983年反复防治,至1989年新发病人数降至11例,基本控制了当地VL的流行.

  7. 137例内脏利什曼病患者临床分析%Clinical Analysis of 137 Patients with Visceral Leishmaniasis

    Institute of Scientific and Technical Information of China (English)

    高芹; 刘焱斌; 钟册俊; 吕晓菊

    2013-01-01

    目的 分析近十几年四川地区内脏利什曼病住院患者临床和流行病学特征.方法 收集2000年1月至2012年4月四川大学华西医院收治的内脏利什曼病患者137例的资料,回顾性分析流行病学、临床特点、治疗和转归.结果 137例患者中,64.2% (88/137)居住在四川及周边内脏利什曼病流行区,35.8% (49/137)有流行区逗留史.137例中,农村占84.7% (116/137),城镇占15.3% (21/137).临床表现以发热,肝、脾及淋巴结肿大,全血细胞减少和球蛋白明显增高为主.137例患者利什曼原虫rk39抗体试纸条检测均为阳性.诊断明确者用葡萄糖酸锑钠治疗.治愈118例(86.1%),脾切除4例(2.9%),复发9例(6.6%).137例中首诊疑诊为内脏利什曼病者105例,误诊率为23.4% (32/137).结论 关注流行病学史、检测rk39抗体,以及尽早骨髓涂片或组织活检有助于早期诊治,葡萄糖酸锑钠疗效较好.%Objective To analyze the clinical and epidemiological characteristics of visceral leishmaniasis cases in Sichuan. Methods The medical records of 137 patients with visceral leishmaniasis were reviewed between January 2000 and April 2012 in West China Hospital. The epidemiological data, clinical manifestations, laboratory features, diagnosis, therapeutic procedures and outcome of the patients were retrospectively analyzed. Results Eighty-eight(64.2%) out of 137 cases were the residents in the endemic area of Sichuan Province and adjacent areas, and 49 (35.8%) were non-endemic area residents with a history of visiting endemic area. Patients living in rural areas accounted for 84.7%(116/137), in town for 15.3% (21/137). Visceral leishmaniasis should be strongly suspected in a patient with prolonged fever, marked hepatosplenomegaly, Iymphadenectasis, cytopenia and hypergammaglobulinemia. All patients showed positive in rk39 dipstick test, and were treated with antimony sodium gluconate. Among these patients, 86.1% (118/137) were cured by

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

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    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.

  9. First description of autochthonous canine visceral leishmaniasis in the metropolitan region of Vitória, State of Espírito Santo, Brazil

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    Marco André Loureiro Tonini

    2012-12-01

    Full Text Available INTRODUCTION: We investigated autochthonous canine visceral leishmaniasis (CVL in the metropolitan region of Vitória (MRV, an area in which a human case was previously reported. METHODS: Serological, parasitological, and molecular tests were performed in 201 dogs. RESULTS: Twenty-six (13% and 12 (6% dogs were identified as positive using in-house enzyme-linked immunosorbent assay (ELISA and rK39 tests, respectively. Two dogs had a positive culture for Leishmania chagasi, and 4 were polymerase chain reaction (PCR-positive for Leishmania spp. One positive dog belonged to the aforementioned patient. CONCLUSIONS: Although the responsible vector was not found, our results provide evidence of autochthonous CVL in the MRV, a non-endemic area for VL.

  10. Species composition and relative abundance of sand flies of the genus Lutzomyia (Diptera: Psychodidae) at an endemic focus of visceral leishmaniasis in Colombia.

    Science.gov (United States)

    Ferro, C; Morrison, A C; Torres, M; Pardo, R; Wilson, M L; Tesh, R B

    1995-07-01

    Ecological studies on the sand fly Lutzomyia longipalpis (Lutz & Neiva) were conducted during 1990-1993 at a small rural community in Colombia where American visceral leishmaniasis is endemic. Weekly sand fly collections were made from pigpens, houses, and natural resting sites, using hand-held aspirators, sticky (oiled) paper traps, and opossum-baited Disney traps. In total, 263,094 sand flies were collected; L. longipalpis predominated (86.1%), followed by L. trinidadensis (11.0%), L. cayennensis (2.7%), and 8 other Lutzomyia species. The species composition and sex ratio of these sand flies varied among sites and by collection method. L. longipalpis were captured most efficiently by direct aspiration from animal bait. Conversely, sticky paper traps, especially inside houses and at rock resting sites, collected a greater diversity of species, but a lower relative abundance of L. longipalpis.

  11. Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates with Active Visceral Disease in Humans

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    Begoña Pérez-Cabezas

    2016-11-01

    Full Text Available The complexity of Leishmania-host interactions, one of the main leishmaniasis issues, is yet to be fully understood. We detected elevated IL-27 plasma levels in European patients with active visceral disease caused by Leishmania infantum, which returned to basal levels after successful treatment, suggesting this cytokine as a probable infection mediator. We further addressed this hypothesis recurring to two classical susceptible visceral leishmaniasis mouse models. BALB/c, but not C57BL/6 mice, showed increased IL-27 systemic levels after infection, which was associated with an upregulation of IL-27p28 expression by dendritic cells and higher parasite burdens. Neutralization of IL-27 in acutely infected BALB/c led to decreased parasite burdens and a transient increase in IFN-γ+ splenic T cells, while administration of IL-27 to C57BL/6 promoted a local anti-inflammatory cytokine response at the site of infection and increased parasite loads. Overall we show that, as in humans, BALB/c IL-27 systemic levels are infection-dependently upregulated and may favor parasite installation by controlling inflammation.

  12. Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates with Active Visceral Disease in Humans

    Science.gov (United States)

    Pérez-Cabezas, Begoña; Cecílio, Pedro; Robalo, Ana Luisa; Silvestre, Ricardo; Carrillo, Eugenia; Moreno, Javier; San Martín, Juan V.; Vasconcellos, Rita; Cordeiro-da-Silva, Anabela

    2016-01-01

    The complexity of Leishmania–host interactions, one of the main leishmaniasis issues, is yet to be fully understood. We detected elevated IL-27 plasma levels in European patients with active visceral disease caused by Leishmania infantum, which returned to basal levels after successful treatment, suggesting this cytokine as a probable infection mediator. We further addressed this hypothesis recurring to two classical susceptible visceral leishmaniasis mouse models. BALB/c, but not C57BL/6 mice, showed increased IL-27 systemic levels after infection, which was associated with an upregulation of IL-27p28 expression by dendritic cells and higher parasite burdens. Neutralization of IL-27 in acutely infected BALB/c led to decreased parasite burdens and a transient increase in IFN-γ+ splenic T cells, while administration of IL-27 to C57BL/6 promoted a local anti-inflammatory cytokine response at the site of infection and increased parasite loads. Overall, we show that, as in humans, BALB/c IL-27 systemic levels are infection dependently upregulated and may favor parasite installation by controlling inflammation. PMID:27867384

  13. Study of sand fly fauna in an endemic area of American cutaneous leishmaniasis and canine visceral leishmaniasis in the municipality of Espírito Santo do Pinhal, São Paulo, Brazil.

    Science.gov (United States)

    Colla-Jacques, Fernanda Elisa; Casanova, Cláudio; Prado, Angelo Pires do

    2010-03-01

    Canine American visceral leishmaniasis and American cutaneous leishmaniasis (ACL) cases have been recorded in Espírito Santo do Pinhal. The aim of this study was to gather knowledge of the sand fly community and its population ecology within the municipality. Captures were made weekly over a period of 15 months in the urban, periurban and rural areas of the municipality, using automatic light traps. A total of 5,562 sand flies were collected, comprising 17 species. The most abundant species were Nyssomyia whitmani and Pintomyia pessoai in the rural area, Lutzomyia longipalpis and Ny. whitmani in the periurban area and Lu. longipalpis in the urban area. The highest species richness and greatest index species diversity were found in the rural area. The similarity index showed that urban and periurban areas were most alike. Lu. longipalpis was found in great numbers during both dry and humid periods. The presence of dogs infected with Leishmania infantum chagasi in the urban area indicates a high risk for the establishment of the disease in the region. A high abundance of Ny. whitmani and Pi. pessoai in the rural and periurban areas indicates the possibility of new cases of ACL occurring in and spreading to the periurban area of Espírito Santo do Pinhal.

  14. Study of sand fly fauna in an endemic area of American cutaneous leishmaniasis and canine visceral leishmaniasis in the municipality of Espírito Santo do Pinhal, São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Fernanda Elisa Colla-Jacques

    2010-03-01

    Full Text Available Canine American visceral leishmaniasis and American cutaneous leishmaniasis (ACL cases have been recorded in Espírito Santo do Pinhal. The aim of this study was to gather knowledge of the sand fly community and its population ecology within the municipality. Captures were made weekly over a period of 15 months in the urban, periurban and rural areas of the municipality, using automatic light traps. A total of 5,562 sand flies were collected, comprising 17 species. The most abundant species were Nyssomyia whitmani and Pintomyia pessoai in the rural area, Lutzomyia longipalpis and Ny. whitmani in the periurban area and Lu. longipalpis in the urban area. The highest species richness and greatest index species diversity were found in the rural area. The similarity index showed that urban and periurban areas were most alike. Lu. longipalpis was found in great numbers during both dry and humid periods. The presence of dogs infected with Leishmania infantum chagasi in the urban area indicates a high risk for the establishment of the disease in the region. A high abundance of Ny. whitmani and Pi. pessoai in the rural and periurban areas indicates the possibility of new cases of ACL occurring in and spreading to the periurban area of Espírito Santo do Pinhal.

  15. Identification and phylogenetic relationship of Iranian strains of various Leishmania species isolated from cutaneous and visceral cases of leishmaniasis based on N-acetylglucosamine-1-phosphate transferase gene.

    Science.gov (United States)

    Hajjaran, Homa; Mohebali, Mehdi; Teimouri, Aref; Oshaghi, Mohammad Ali; Mirjalali, Hamed; Kazemi-Rad, Elham; Shiee, Mohammad Reza; Naddaf, Saied Reza

    2014-08-01

    The identity of Iranian Leishmania species has been resolved to some extent by some genetic markers. In this study, based on N-acetylglucosamine-1-phosphate transferase (nagt) gene, we further elucidated the identity and phylogeny of the prevalent species in this country. DNAs of 121 isolates belonging to cutaneous leishmaniasis (CL) patients, canine visceral leishmaniasis (CVL) cases, and Rhombomys opimus rodents were amplified by targeting a partial sequence of nagt gene. All the amplicons were analyzed with restriction fragment length polymorphism (RFLP) using Acc1 enzyme, and 49 amplicons representing different reservoir hosts were sequenced and aligned with similar sequences from GenBank database. The RFLP analysis revealed that 41 CL patients were infected Leishmania tropica and 36 with Leishmania major. Among 10 CVL isolates, 6 were identified as Leishmania infantum and 4 as L. tropica. Amongst 34 rodents' isolates, 11 and 23 isolates exhibited patterns similar to those of L. major, and L. tropica/Leishmania turanica, respectively. The sequencing results from all CL patients, CVL cases, and 4 reservoir rodents were in agreement with RFLP analysis and showed 99-100% homologies with the registered species of L. major, L. tropica, and L. infantum from Turkey, Tunisia, Iraq and Israel. Of the 7 rodent isolates exhibiting RFLP patterns similar to L. tropica/L. turanica, 3 exhibited the highest homologies (99-100%) with L. turanica and 4 with Leishmania gerbilli. The 49 nagt DNA sequences were grouped into five clusters representing L. major, L. tropica, L. infantum, L. turanica and L. gerbilli species, encompassing 19 haplotypes. No correlation was observed between intraspecies divergence and geographic distribution of haplotypes. The L. tropica haplotypes exhibited more homologies with those of L. infantum than L. major (97.2% vs. 96.9%), a probable indication to the potential ability of L. tropica to visceralize. Characterization of Iranian Leishmania isolates

  16. Vaccination with liposomal leishmanial antigens adjuvanted with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) confers long-term protection against visceral leishmaniasis through a human administrable route.

    Science.gov (United States)

    Ravindran, Rajesh; Maji, Mithun; Ali, Nahid

    2012-01-01

    The development of a long-term protective subunit vaccine against visceral leishmaniasis depends on antigens and adjuvants that can induce an appropriate immune response. The immunization of leishmanial antigens alone shows limited efficacy in the absence of an appropriate adjuvant. Earlier we demonstrated sustained protection against Leishmania donovani with leishmanial antigens entrapped in cationic liposomes through an intraperitoneal route. However, this route is not applicable for human administration. Herein, we therefore evaluated the immune response and protection induced by liposomal soluble leishmanial antigen (SLA) formulated with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) through a subcutaneous route. Subcutaneous immunization of BALB/c mice with SLA entrapped in liposomes or with MPL-TDM elicited partial protection against experimental visceral leishmaniasis. In contrast, liposomal SLA adjuvanted with MPL-TDM induced significantly higher levels of protection in liver and spleen in BALB/c mice challenged 10 days post-vaccination. Protection conferred by this formulation was sustained up to 12 weeks of immunization, and infection was controlled for at least 4 months of the challenge, similar to liposomal SLA immunization administered intraperitoneally. An analysis of cellular immune responses of liposomal SLA + MPL-TDM immunized mice demonstrated the induction of IFN-γ and IgG2a antibody production not only 10 days or 12 weeks post-vaccination but also 4 months after the challenge infection and a down regulation of IL-4 production after infection. Moreover, long-term immunity elicited by this formulation was associated with IFN-γ production also by CD8⁺ T cells. Taken together, our results suggest that liposomal SLA + MPL-TDM represent a good vaccine formulation for the induction of durable protection against L. donovani through a human administrable route.

  17. Pharmacokinetic and parasitological evaluation of the bone marrow of dogs with visceral leishmaniasis submitted to multiple dose treatment with liposome-encapsulated meglumine antimoniate

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    D.A. Schettini

    2005-12-01

    Full Text Available The aim of the present study was to evaluate the impact of a multiple dose regimen of a liposomal formulation of meglumine antimoniate (LMA on the pharmacokinetics of antimony in the bone marrow of dogs with visceral leishmaniasis and on the ability of LMA to eliminate parasites from this tissue. Dogs naturally infected with Leishmania chagasi received 4 intravenous doses of either LMA (6.5 mg antimony/kg body weight, N = 9, or empty liposomes (at the same lipid dose as LMA, N = 9 at 4-day intervals. A third group of animals was untreated (N = 8. Before each administration and at different times after treatment, bone marrow was obtained and analyzed for antimony level (LMA group by electrothermal atomic absorption spectrometry, and for the presence of Leishmania parasites (all groups. There was a significant increase of antimony concentration from 0.76 µg/kg wet organ (4 days after the first dose to 2.07 µg/kg (4 days after the fourth dose and a half-life of 4 days for antimony elimination from the bone marrow. Treatment with LMA significantly reduced the number of dogs positive for parasites (with at least one amastigote per 1000 host cells compared to controls (positive dogs 30 days after treatment: 0 of 9 in the LMA group, 3 of 9 in the group treated with empty liposomes and 3 of 8 in the untreated group. However, complete elimination of parasites was not achieved. In conclusion, the present study showed that multiple dose treatment with LMA was effective in improving antimony levels in the bone marrow of dogs with visceral leishmaniasis and in reducing the number of positive animals, even though it was not sufficient to achieve complete elimination of parasites.

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

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    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. 

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

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    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.

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

    Science.gov (United States)

    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.

  1. Ecological aspects of phlebotomines (Diptera: Psychodidae) in endemic area of visceral leishmaniasis, Campo Grande, State of Mato Grosso do Sul, Brazil.

    Science.gov (United States)

    Oliveira, Alessandra Gutierrez; Galati, Eunice Aparecida Bianchi; Fernandes, Carlos Eurico; Dorval, Maria Elizabeth Cavalheiros; Brazil, Reginaldo Peçanha

    2012-01-01

    Aspects of phlebotomine behavior were investigated in the city of Campo Grande, Mato Grosso do Sul state. The insects were captured weekly during December 2003 to November 2005, with Centers for Disease Control light traps at seven different sites including forests and residential areas. In total, 11,024 specimens (7,805 males and 3,219 females) were collected, from which 9,963 (90.38%) were identified as Lutzomyia longipalpis, the proven vector of American visceral leishmaniasis agent. The remaining 9.62% comprised 21 species. L. longipalpis was the most frequent species in all sampled sites, and the first in the ranking of standardized species abundance index. In residential areas this species clearly predominated in the peridomicile (90.96%), in contrast to the intradomicile (9.04%); in animal shelters, it was more numerous in hen houses and prevailed at ground level, inside, and at forest edge around the residences; this aspect is worrying because this insect may remain sheltered in forested environments during the use of insecticides in homes. In the forest environment, other probable or proven vector of cutaneous leishmaniasis agents were also captured such as Lutzomyia whitmani (=Nyssomyia whitmani, sensu Galati), Lutzomyia antunesi (=Nyssomyia antunesi, sensu Galati), and Lutzomyia flaviscutellata (=Bichromomyia flaviscutellata, sensu Galati).

  2. Clinical Features and Laboratory Findings of Visceral Leishmaniasis in Children Referred To Children Medical Center Hospital, Tehran, Iran during 2004-2011.

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    Azam Tofighi Naeem

    2014-03-01

    Full Text Available Visceral leishmaniasis (VL is one of the most important parasitic diseases endemic in northwestern and southern areas of Iran. The aim of the present study was to review the records of children hospitalized with VL in order to characterize the clinical features of children as well as laboratory finding in Children Medical Center Hospital, Tehran, Iran.The medical records of all children with a final diagnosis of VL were reviewed from 2004 to 2011. Demographic, clinical information, laboratory finding and treatment were considered.A total number of 34 children with confirmed VL through 2004-2011 were included in the study. The most prevalent sign and symptoms were fever (97.1%, pallor and weakness (97.1%, appetite loss (61.8%, splenomegaly (97.1% and hepatomegaly (88.2%. The most frequent laboratory abnormalities were hematological including anemia (97.1%, thrombocytopenia (91.2% and leukopenia (67.6%. Direct agglutination test (DAT was performed in 23 cases and all of them showed anti-Leishmania antibodies with titers of ≥ 1: 3200. In addition, 90% of patients had positive rK39 results. Identification of Leishmania in the aspirates of the bone marrow was found in 83.3% of patients.Regional surveillance system in order to monitoring of leishmaniasis trends as well as detection of new emerging foci is recommended.

  3. 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

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    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.

  4. 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

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    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

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

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    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

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

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    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

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

    Science.gov (United States)

    Martins, Vivian Tamietti; Chávez-Fumagalli, Miguel Angel; Lage, Daniela Pagliara; Duarte, Mariana Costa; Garde, Esther; Costa, Lourena Emanuele; da Silva, Viviane Gomes; Oliveira, Jamil Silvano; de Magalhães-Soares, Danielle Ferreira; Teixeira, Santuza Maria Ribeiro; Fernandes, Ana Paula; Soto, Manuel; Tavares, Carlos Alberto Pereira; Coelho, Eduardo Antonio Ferraz

    2015-01-01

    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 parasite

  8. Leishmaniasis in the knee area

    Institute of Scientific and Technical Information of China (English)

    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.

  9. Laryngeal leishmaniasis in Malta.

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    Fsadni, C; Fsadni, P; Piscopo, T; Mallia Azzopardi, C

    2007-02-01

    The localization of Leishmania spp. in the larynx is rare especially when not associated with immunosuppression or with visceral or cutaneous leishmaniasis. We present a case of isolated laryngeal leishmaniasis, the first of its kind documented in Malta and infrequently reported from the Mediterranean basin.

  10. A review of Leishmaniasis in Eastern Africa

    Institute of Scientific and Technical Information of China (English)

    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.

  11. Usefulness of the rK39-immunochromatographic test, direct agglutination test, and leishmanin skin test for detecting asymptomatic Leishmania infection in children in a new visceral leishmaniasis focus in Amhara State, Ethiopia.

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    Gadisa, Endalamaw; Custodio, Estefanía; Cañavate, Carmen; Sordo, Luis; Abebe, Zelalem; Nieto, Javier; Chicharro, Carmen; Aseffa, Abraham; Yamuah, Lawrence; Engers, Howard; Moreno, Javier; Cruz, Israel

    2012-05-01

    In areas where visceral leishmaniasis is anthroponotic, asymptomatically infected patients may play a role in transmission. Additionally, the number of asymptomatic patients in a disease-endemic area will also provide information on transmission dynamics. Libo Kemkem and Fogera districts (Amhara State, Ethiopia) are now considered newly established areas to which visceral leishmaniasis is endemic. In selected villages in these districts, we conducted a study to assess the usefulness of different approaches to estimate the asymptomatic infection rate. Of 605 participants, the rK39 immunochromatographic test was able to detect asymptomatic infection in 1.5% (9 of 605), direct agglutination test in 5.3% (32 of 605), and leishmanin skin test in 5.6% (33 of 589); the combined use of serologic methods and leishmanin skin test enabled detecting asymptomatic infection in 10.1% (61 of 605). We conclude that the best option to detect asymptomatic infection in this new visceral leishmaniasis-endemic focus is the combined use of the direct agglutination test and the leishmanin skin test.

  12. Study of sand flies (Diptera: Psychodidae) in visceral and cutaneous leishmaniasis areas in the central-western state of Minas Gerais, Brazil.

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    Nascimento, Bruno Warlley Leandro; Saraiva, Lara; Neto, Rafael Gonçalves Teixeira; Meira, Paula Cavalcante Lamy Serra e; Sanguinette, Cristiani de Castilho; Tonelli, Gabriel Barbosa; Botelho, Helbert Antônio; Belo, Vinícius Silva; Silva, Eduardo Sérgio da; Gontijo, Célia Maria Ferreira; Filho, José Dilermando Andrade

    2013-03-01

    The transmission of Leishmania involves several species of sand flies that are closely associated with various parasites and reservoirs, with differing transmission cycles in Brazil. A study on the phlebotomine species composition has been conducted in the municipality of Divinópolis, Minas Gerais, Brazil, an endemic area for cutaneous leishmaniasis (CL), which has intense occurrence of visceral leishmaniasis (VL) cases. In order to study the sand flies populations and their seasonality, CDC light traps (HP model) were distributed in 15 houses which presented at least one case of CL or VL and in five urban parks (green areas). Collections were carried out three nights monthly from September 2010 to August 2011. A total of 1064 phlebotomine specimens were collected belonging to two genera and seventeen species: Brumptomyia brumpti, Lutzomyia bacula, Lutzomyia cortelezzii, Lutzomyia lenti, Lutzomyia sallesi, Lutzomyia longipalpis, Lutzomyia migonei, Lutzomyia intermedia, Lutzomyia neivai, Lutzomyia whitmani, Lutzomyia christenseni, Lutzomyia monticola, Lutzomyia pessoai, Lutzomyia aragaoi, Lutzomyia brasiliensis, Lutzomyia lutziana, and Lutzomyia sordellii. L. longipalpis, the main vector of Leishmania infantum in Brazil, was the most frequent species, accounting for 76.9% of the total, followed by L. lenti with 8.3%, this species is not a proven vector. Green and urban areas had different sand flies species composition, whereas the high abundance of L. longipalpis in urban areas and the presence of various vector species in both green and urban areas were also observed. Our data point out to the requirement of control measures against phlebotomine sand flies in the municipality of Divinópolis and adoption of strategies aiming entomological surveillance.

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

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    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.

  14. Polyclonal hypergammaglobulinemia and high smooth-muscle autoantibody titers with specificity against filamentous actin: consider visceral leishmaniasis, not just autoimmune hepatitis.

    Science.gov (United States)

    Makaritsis, Konstantinos P; Gatselis, Nikolaos K; Ioannou, Maria; Petinaki, Efthimia; Dalekos, George N

    2009-07-01

    Visceral leishmaniasis (VL) remains a public health problem in most countries bordering the Mediterranean basin. Its diagnosis is challenging and often delayed, as the main clinical picture is often indistinguishable from that of other infectious and non-infectious diseases. Herein, we report two unusual cases of VL that presented with several characteristics of autoimmune hepatitis (AIH). Neither patient had a history of fever, only generalized symptoms accompanied by polyclonal hypergammaglobulinemia, cytopenias, signs of portal hypertension, elevated transaminases, and high titers of antinuclear and smooth-muscle autoantibodies (SMA) with reactivity against filamentous actin (F-actin), which has been recognized as specific to AIH. A clinical diagnosis of AIH was considered, but a bone marrow biopsy was performed before a liver biopsy to exclude a primary bone marrow disease. The biopsy led to the diagnosis of VL. The diagnosis was further confirmed by IgG antibodies against Leishmania spp. using ELISA and PCR-based assays. Treatment with amphotericin in the first case and pentamidine in the second (because of a severe reaction to amphotericin) was effective. From the clinical point of view, it should be emphasized that, in cases with high titers of anti-F-actin AIH-specific SMA accompanied by polyclonal hypergammaglobulinemia, the possibility of AIH should be cautiously differentiated from VL; this distinction is of paramount importance because initiation of immunosuppression for AIH treatment would be detrimental to a patient with underlying leishmaniasis. Therefore, in such cases and in areas where the disease is still present, it seems rational to exclude VL before starting any immunosuppressive therapy.

  15. Use of Pentamidine As Secondary Prophylaxis to Prevent Visceral Leishmaniasis Relapse in HIV Infected Patients, the First Twelve Months of a Prospective Cohort Study.

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    Ermias Diro

    Full Text Available Visceral leishmaniasis (VL has become an important opportunistic infection in persons with HIV-infection in VL-endemic areas. The co-infection leads to profound immunosuppression and high rate of annual VL recurrence. This study assessed the effectiveness, safety and feasibility of monthly pentamidine infusions to prevent recurrence of VL in HIV co-infected patients.A single-arm, open-label trial was conducted at two leishmaniasis treatment centers in northwest Ethiopia. HIV-infected patients with a VL episode were included after parasitological cure. Monthly infusions of 4 mg/kg pentamidine-isethionate diluted in normal-saline were started for 12 months. All received antiretroviral therapy (ART. Time-to-relapse or death was the primary end point.Seventy-four patients were included. The probability of relapse-free survival at 6 months and at 12 months was 79% and 71% respectively. Renal failure, a possible drug-related serious adverse event, occurred in two patients with severe pneumonia. Forty-one patients completed the regimen taking at least 11 of the 12 doses. Main reasons to discontinue were: 15 relapsed, five died and seven became lost to follow-up. More patients failed among those with a CD4+cell count ≤ 50 cells/μl, 5/7 (71.4% than those with counts above 200 cells/μl, 2/12 (16.7%, (p = 0.005.Pentamidine secondary prophylaxis led to a 29% failure rate within one year, much lower than reported in historical controls (50%-100%. Patients with low CD4+cell counts are at increased risk of relapse despite effective initial VL treatment, ART and secondary prophylaxis. VL should be detected and treated early enough in patients with HIV infection before profound immune deficiency installs.

  16. Epidemiological aspects of vector, parasite, and domestic reservoir in areas of recent transmission and no reported human cases of visceral leishmaniasis in Brazil.

    Science.gov (United States)

    Lara-Silva, Fabiana de Oliveira; Michalsky, Érika Monteiro; Fortes-Dias, Consuelo Latorre; Fiuza, Vanessa de Oliveira Pires; Pessanha, José Eduardo Marques; Regina-Silva, Shara; de Avelar, Daniel Moreira; Silva, Maiara Alves; Lima, Ana Cristina Vianna Mariano da Rocha; da Costa, Ailton Junior Antunes; Machado-Coelho, George Luiz Lins; Dias, Edelberto Santos

    2015-08-01

    About 97% of the human cases of the American visceral leishmaniasis (VL) occur in Brazil. In the last few years, the disease expanded to medium- and large-sized cities, in which surveillance and control actions have been intensified, in an effort to control VL spreading. Our two-year study was conducted in Belo Horizonte, the sixth most populous city in Brazil, which is endemic for VL. We focused in two particular districts of recent transmission of the disease, with no reported human cases and submitted to minor surveillance and control actions. Our aim was to draw an epidemiological profile of the local situation concerning Lutzomyia vector, Leishmania parasites, and the main domestic reservoirs (dogs). Lutzomyia longipalpis comprised 96.5% of the total phlebotomine sand flies captured and displayed an expressive minimal infection rate by Leishmania infantum (16.7%). Positive correlations were found between the population densities of L. longipalpis, rainfall and temperature. L. infantum was also detected in the cortelezzii complex and, for the first time, in Lutzomyia lloydi. Leishmania braziliensis, an etiological agent of the American cutaneous leishmaniasis, was also identified in L. longipalpis. Among the 1408 dogs serologically tested by standard enzyme-linked and fluorescence immune assays (ELISA/IFA) 3.6% were positive for VL. L. infantum DNA and Leishmania parasites were identified in 100% and 72.5% of the seropositive dogs, respectively. The co-positivity of other diagnostic tests for VL-Leishmania-nested PCR, imprint and myeloculture-was compared to the standard serology. Both symptomatic or asymptomatic dogs displayed an equal average number of positive diagnostic tests for VL. The districts studied display favorable conditions for the rapid spreading of human infection, in terms of L. longipalpis population density, and presence of L. infantum in both vector and main reservoir.

  17. Longitudinal analysis of serological tests officially adopted by the Brazilian Ministry of Health for the diagnosis of canine visceral leishmaniasis in dogs vaccinated with Leishmune®.

    Science.gov (United States)

    Marcondes, Mary; de Lima, Valéria Marçal Félix; de Araújo, Maria de Fátima Lereno; Hiramoto, Roberto Mitsuyoshi; Tolezano, José Eduardo; Vieira, Rafael F C; Biondo, Alexander W

    2013-11-08

    Development of vaccines against canine visceral leishmaniasis (CVL) may provide a prophylactic barrier, but antibody response detected by standard diagnostic techniques may not separate vaccinated from naturally infected dogs. Moreover, anti-Leishmania antibody levels in vaccinated dogs may be detectable for months. Accordingly, the aim of the present study was to comparatively evaluate an "in-house" ELISA with three serological tests officially adopted by the Brazilian Ministry of Health for the diagnosis of CVL in dogs vaccinated with Leishmune(®). A total of 18 mongrel dogs were submitted to a complete protocol of the vaccine, monitored and evaluated in 5 times (T0-T4) up to 180 days after T0. Twenty-one days after the first dose (T1), 50% of the dogs were seropositive by the "in-house" ELISA and 5.5% by IFAT, while by the official ELISA and DPP(®) CVL rapid test all dogs tested negative. At time T2, 42 days after of the first dose, 100%, 83.3%, 11.1%, and 5.5% of the dogs were seropositive by the "in-house" ELISA, IFAT, official ELISA kit and the DPP(®) CVL rapid test, respectively. Ninety days after the first dose (T3), 100%, 83.3%, 72.2% and 33.3% of the dogs were seropositive by the "in-house" ELISA, official ELISA kit, IFAT, and the DPP(®) CVL rapid test, respectively. Finally, at time T4, 88.8%, 33.3%, 11.1% and 5.5% of the dogs were seropositive by the "in-house" ELISA, official ELISA kit, DPP(®) CVL rapid test and IFAT, respectively. In conclusion, dogs vaccinated with Leishmune(®) cross-react by an "in-house" ELISA and by the three official Brazilian serological tests for the diagnosis of canine visceral leishmaniasis up to six months after the first vaccine dose, and may be mistakenly diagnosed and removed.

  18. Canine visceral leishmaniasis: a comparative study of real-time PCR, conventional PCR, and direct agglutination on sera for the detection of Leishmania infantum infection.

    Science.gov (United States)

    Mohammadiha, A; Haghighi, A; Mohebali, M; Mahdian, R; Abadi, A R; Zarei, Z; Yeganeh, F; Kazemi, B; Taghipour, N; Akhoundi, B; Barati, M; Mahmoudi, M R

    2013-02-18

    Canine visceral leishmaniasis (CVL) is endemic in northwestern Iran. This study aimed to compare real-time PCR, conventional PCR, and the direct agglutination test (DAT) for the diagnosis Leishmania infantum infection in 167 serum samples of domestic dog. Bone marrow was used for parasitological examination (smears and/or culture) in symptomatic visceral leishmaniasis, and serum was used for detection of L. infantum kinetoplast DNA (kDNA) by both conventional PCR and real-time PCR, while anti-L. infantum antibodies in sera were measured by DAT. The sera were collected from 37 symptomatic and 112 asymptomatic dogs during April to May 2011. Eighteen presumed negative samples were obtained from healthy dogs kept in non-endemic areas with no history of CVL and used as controls. All 18 samples were negative by DAT and Dipstick rK39. DAT confirmed previous exposure to L. infantum for all 149 serum samples collected from symptomatic and asymptomatic dogs in CVL endemic areas of Iran. Among the 37 symptomatic dogs, 20 (54%), 25 (67.6%), 36 (97.3%), and 37 (100%) showed L. infantum infection by parasitological methods, conventional PCR, real-time PCR, and DAT (≥ 1:80), respectively. Of 112 asymptomatic dogs, 79 (70.5%), 111 (99.1%), and 112 (100%) were shown to be positive by conventional PCR, and DAT (≥ 1:80), respectively. For ethical reasons, no asymptomatic or healthy control dogs were examined by parasitological methods. Three (16.7%) control dogs were positive by real-time PCR, but were negative by DAT, dipstick rK39, and conventional PCR methods. Parasitemia levels were measured by real-time PCR targeting kDNA using SYBR(®) green assay. This quantitative technique detected infection in 89.9% (150/167) of the domestic dogs that harbored L. infantum kDNA, ranging from 0.01 49 to 310.1 parasites/ml. The average was 16.60 parasites/ml. A good agreement (0.97) was found between real-time PCR and DAT at ≥ 1:80 titer, used as cut-off value by Kappa analysis. Thus

  19. 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

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    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

  20. The Seminested PCR Based Detection of Leishmania infantum Infection in Asymptomatic Dogs in a New Endemic Focus of Visceral Leishmaniasis in Iran

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    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.

  1. Morphometric and morphological variation between two different populations of Phlebotomus major s.l. from endemic and non-endemic foci of visceral leishmaniasis in Iran.

    Science.gov (United States)

    Badakhshan, Mehdi; Sadraei, Javid; Moin-Vaziri, Vahideh

    2011-06-01

    Populations of Phlebotomus major were examined in two endemic and nonendemic foci of visceral leishmaniasis in Iran. Based on the shape of the aedeagus and ventrally located hairs of coxite and pharyngeal armatures, two morphotypes were found sympatrically in the endemic area of Borazjan. Significant differences in morphometric survey were observed in at least 11 measured characters. The aedeagus of the non-endemic Miyandoab morphotype, and also of a few specimens from Borazjan, is completely parallel throughout its length with a slightly expanded end. Ventrally located hairs of the middle coxite were longer and more compact. It is close morphologically to P. major neglectus (P. neglectus), which was recently recorded from Iran. It is also morphologically similar to P. notus, which has not yet been reported from Iran and needs further investigation. The aedeagus of the morphotype occurring only in Borazjan is narrower in the middle and the hairs are closer to the base of the coxite and are shorter and more outspread, which makes it similar to P. major krimensis or P. neglectus. The two morphotypes occurring sympatrically in Borazjan do not appear to be subspecies and it may be premature to propose them as separate species. Further investigation is needed to clarify the actual status of P. major s. l. in Iran.

  2. Studies on the protective efficacy of freeze thawed promastigote antigen of Leishmania donovani along with various adjuvants against visceral leishmaniasis infection in mice.

    Science.gov (United States)

    Thakur, Ankita; Kaur, Harpreet; Kaur, Sukhbir

    2015-09-01

    Visceral leishmaniasis (VL) caused by Leishmania donovani persists as a major public health issue in tropical and subtropical areas of the world. Current treatment of this disease relies on use of drugs. It is doubtful that chemotherapy can alone eradicate the disease, so there is a need for an effective vaccine. Killed antigen candidates remain a good prospect considering their ease of formulation, stability, low cost and safety. To enhance the efficacy of killed vaccines suitable adjuvant and delivery system are needed. Therefore, the current study was conducted to determine the protective efficacy of freeze-thawed L. donovani antigen in combination with different adjuvants against experimental infection of VL. For this, BALB/c mice were immunized thrice at an interval of two weeks. Challenge infection was given two weeks after last immunization. Mice were sacrificed after last immunization and on different post challenge/infection days. Immunized mice showed significant reduction in parasite burden, enhanced DTH responses with increased levels of Th1 cytokines and lower levels of Th2 cytokines, thus indicating the development of a protective Th1 response. Maximum protection was achieved with liposome encapsulated freeze thawed promastigote (FTP) antigen of L. donovani and it was followed by group immunized with FTP+MPL-A, FTP+saponin, FTP+alum and FTP antigen (alone). The present study highlights greater efficacy of freeze thawed promastigote antigen as a potential vaccine candidate along with effective adjuvant formulations against experimental VL infection.

  3. Identification of Leishmania infantum chagasi proteins in urine of patients with visceral leishmaniasis: a promising antigen discovery approach of vaccine candidates.

    Science.gov (United States)

    Kashino, S S; Abeijon, C; Qin, L; Kanunfre, K A; Kubrusly, F S; Silva, F O; Costa, D L; Campos, D; Costa, C H N; Raw, I; Campos-Neto, A

    2012-07-01

    Visceral leishmaniasis (VL) is a serious lethal parasitic disease caused by Leishmania donovani in Asia and by Leishmania infantum chagasi in southern Europe and South America. VL is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. This high incidence is due in part to the lack of an efficacious vaccine. Here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with VL. We combined RP-HPLC and mass spectrometry and categorized three L. infantum chagasi proteins, presumably produced in spleen, liver and bone marrow lesions and excreted in the patients' urine. Specifically, these proteins were the following: Li-isd1 (XP_001467866.1), Li-txn1 (XP_001466642.1) and Li-ntf2 (XP_001463738.1). Initial vaccine validation studies were performed with the rLi-ntf2 protein produced in Escherichia coli mixed with the adjuvant BpMPLA-SE. This formulation stimulated potent Th1 response in BALB/c mice. Compared to control animals, mice immunized with Li-ntf2+ BpMPLA-SE had a marked parasite burden reduction in spleens at 40 days post-challenge with virulent L. infantum chagasi. These results strongly support the proposed antigen discovery strategy of vaccine candidates to VL and opens novel possibilities for vaccine development to other serious infectious diseases.

  4. Distribution of phlebotomine fauna (Diptera: Psychodidae across an urban-rural gradient in an area of endemic visceral leishmaniasis in northern Brazil

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    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.

  5. Sand fly vectors (Diptera, Psychodidae) of American visceral leishmaniasis areas in the Atlantic Forest, State of Espírito Santo, southeastern Brazil.

    Science.gov (United States)

    Pinto, Israel de Souza; Ferreira, Adelson Luiz; Valim, Valéria; Carvalho, Felipe dos Santos; da Silva, Giovana Marques; Falcão, Alda Lima; Dietze, Reynaldo; Falqueto, Aloísio

    2012-06-01

    The aim of this study was to evaluate the sand fly fauna of American visceral leishmaniasis (AVL) endemic areas within the Central Atlantic Forest Biodiversity Corridor, State of Espírito Santo, southeastern Brazil. The sand fly captures were performed between January, 1989 and December, 2003 in localities where autochthonous cases of AVL were recorded, as well as in their boundary areas. Sand flies were collected from surrounding houses and domestic animal shelters using two to five CDC automatic light traps, and manual captures were also performed using mouth aspirators in one illuminated Shannon trap during the first four hours of the night. We used cladistic analysis to determine the geographic relationships among the collected sand fly species as well as the index species for the occurrence of other sand flies. A total of 62,469 sand flies belonging to 17 species and eight genera was collected in 164 localities from nine municipalities with AVL records. The richness (S=17) and diversity (H=0.971) of sand flies were lower than in conservation areas and similar to modified environments in the Atlantic Forest of Espírito Santo. Lutzomyia longipalpis was identified in 79 localities. The cladistic analysis identified Evandromyia lenti as the index species for Lutzomyia longipalpis. The latter seems to be the main vector of AVL in the Central Atlantic Forest Biodiversity Corridor due to its high abundance and distribution matching the disease occurrence. Therefore, Evandromyia lenti may be used as an index species for the occurrence of Lutzomyia longipalpis.

  6. Distribution of phlebotomine fauna (Diptera: Psychodidae) across an urban-rural gradient in an area of endemic visceral leishmaniasis in northern Brazil.

    Science.gov (United States)

    Oliveira, Davi Marcos Souza de; Saraiva, Elvira Maria; Ishikawa, Edna Aoba Yassui; Sousa, Adelson Alcimar Almeida de; Silva, Edilene Oliveira da; Silva, Ivoneide Maria da

    2011-12-01

    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.

  7. Comparison of Insecticide-Treated Nets and Indoor Residual Spraying to Control the Vector of Visceral Leishmaniasis in Mymensingh District, Bangladesh

    Science.gov (United States)

    Chowdhury, Rajib; Dotson, Ellen; Blackstock, Anna J.; McClintock, Shannon; Maheswary, Narayan P.; Faria, Shyla; Islam, Saiful; Akter, Tangin; Kroeger, Axel; Akhter, Shireen; Bern, Caryn

    2011-01-01

    Integrated vector management is a pillar of the South Asian visceral leishmaniasis (VL) elimination program, but the best approach remains a matter of debate. Sand fly seasonality was determined in 40 houses sampled monthly. The impact of interventions on Phlebotomus argentipes density was tested from 2006–2007 in a cluster-randomized trial with four arms: indoor residual spraying (IRS), insecticide-treated nets (ITNs), environmental management (EVM), and no intervention. Phlebotomus argentipes density peaked in March with the highest proportion of gravid females in May. The EVM (mud plastering of wall and floor cracks) showed no impact. The IRS and ITNs were associated with a 70–80% decrease in male and female P. argentipes density up to 5 months post intervention. Vector density rebounded by 11 months post-IRS, whereas ITN-treated households continued to show significantly lower density compared with households without intervention. Our data suggest that both IRS and ITNs may help to improve VL control in Bangladesh. PMID:21540372

  8. Identification of environmental parameters and risk mapping of visceral leishmaniasis in Ethiopia by using geographical information systems and a statistical approach

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    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. Identification of environmental parameters and risk mapping of visceral leishmaniasis in Ethiopia by using geographical information systems and a statistical approach.

    Science.gov (United States)

    Tsegaw, Teshome; Gadisa, Endalamaw; Seid, Ahmed; Abera, Adugna; Teshome, Aklilu; Mulugeta, Abate; Herrero, Merce; Argaw, Daniel; Jorge, Alvar; Aseffa, Abraham

    2013-05-01

    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.

  10. How effective is dog culling in controlling zoonotic visceral leishmaniasis? a critical evaluation of the science, politics and ethics behind this public health policy

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    Carlos Henrique Nery Costa

    2011-04-01

    Full Text Available INTRODUCTION: Zoonotic kala-azar, a lethal disease caused by protozoa of the genus Leishmania is considered out of control in parts of the world, particularly in Brazil, where transmission has spread to cities throughout most of the territory and mortality presents an increasing trend. Although a highly debatable measure, the Brazilian government regularly culls seropositive dogs to control the disease. Since control is failing, critical analysis concerning the actions focused on the canine reservoir was conducted. METHODS: In a review of the literature, a historical perspective focusing mainly on comparisons between the successful Chinese and Soviet strategies and the Brazilian approach is presented. In addition, analyses of the principal studies regarding the role of dogs as risk factors to humans and of the main intervention studies regarding the efficacy of the dog killing strategy were undertaken. Brazilian political reaction to a recently published systematic review that concluded that the dog culling program lacked efficiency and its effect on public policy were also reviewed. RESULTS: No firm evidence of the risk conferred by the presence of dogs to humans was verified; on the contrary, a lack of scientific support for the policy of killing dogs was confirmed. A bias for distorting scientific data towards maintaining the policy of culling animals was observed. CONCLUSIONS: Since there is no evidence that dog culling diminishes visceral leishmaniasis transmission, it should be abandoned as a control measure. Ethical considerations have been raised regarding distorting scientific results and the killing of animals despite minimal or absent scientific evidence

  11. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.

    Science.gov (United States)

    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.

  12. SLA-PGN-primed dendritic cell-based vaccination induces Th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of PKCβ.

    Science.gov (United States)

    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.

  13. Climatic factors and population density of Lutzomyia longipalpis (Lutz & Neiva, 1912) in an urban endemic area of visceral leishmaniasis in midwest Brazil.

    Science.gov (United States)

    de Oliveira, Everton Falcão; dos Santos Fernandes, Carlos Eurico; Araújo e Silva, Elaine; Brazil, Reginaldo Peçanha; de Oliveira, Alessandra Gutierrez

    2013-12-01

    The life cycle of vectors and the reservoirs that participate in the chain of infectious diseases have a strong relationship with the environmental dynamics of the ecosystems in which they live. Oscillations in population abundance and seasonality of insects can be explained by factors inherent in each region and time period. Therefore, knowledge of the relationship and influence of environmental factors on the population of Lutzomyia longipalpis is necessary because of the high incidence of visceral leishmaniasis (VL) in Brazil. This study evaluates the influence of abiotic variables on the population density and seasonal behavior of L. longipalpis in an urban endemic area of VL in Brazil. The sand fly captures were performed every two months between November, 2009 and November, 2010 in the peridomicile of 13 randomly selected residences. We captured 1,367 specimens of L. longipalpis, and the ratio of male/female flies was 2.86:1. The comparison of the total male specimens in the two seasons showed a statistical difference in the wet season, but there was no significant difference when considering the total females. With respect to climatic variables, a significant negative association was observed only with wind speed. During periods of high wind speeds, the population density of this vector decreased. The presence of L. longipalpis was found in all months of the study with bimodal behavior and population peaks during the wet season.

  14. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis

    Science.gov (United States)

    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

  15. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.

    Directory of Open Access Journals (Sweden)

    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.

  16. Human and canine visceral leishmaniasis in an emerging focus in Araçuaí, Minas Gerais: spatial distribution and socio-environmental factors.

    Science.gov (United States)

    Ursine, Renata Luiz; Dias, João Victor Leite; Morais, Harriman Aley; Pires, Herton Helder Rocha

    2016-07-01

    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.

  17. Knowledge of the Population about Visceral Leishmaniasis Transmission in Endemic Areas near the Banks of the Mossoró River in Northeastern Brazil

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    Camila Fernandes de Amorim

    2015-03-01

    Full Text Available Visceral leishmaniasis (VL is an anthropozoonosis with high prevalence and incidence in the Northeastern region of Brazil. This study aimed to determine whether people living near the Mossoró River in the city of Mossoró, Rio Grande do Norte, have knowledge of VL and to characterize the environmental properties of this region. Questionnaires were administered to 478 residents in three neighborhoods near the Mossoró River, addressing the population’s knowledge about VL and environmental characteristics. Most survey participants were female, with ages between 18 and 40 years, 53.8% had completed primary education, and 61.5% owned pet dogs (p < 0.05. The majority (95.9% showed little knowledge about the characteristics inherent to sandflies, and 85.3% were unaware of the environments preferred by this vector (p < 0.05. Sewage from the homes of respondents was mainly dumped into the river (44.6%, and 76.6% of the respondents complained about the accumulation of garbage in the streets (p < 0.05. The association between education and knowledge about the transmission of VL and preferred vector locations was statistically significant (p < 0.05. The lack of knowledge in the population about VL and the residential environment indicates a risk of maintaining sand fly habitats and hence disease transmission.

  18. Treatment of visceral leishmaniasis: anomalous pricing and distribution of AmBisome and emergence of an indigenous liposomal amphotericin B, FUNGISOME.

    Science.gov (United States)

    Bhattacharya, Pradyot; Ali, Nahid

    2016-09-01

    Visceral leishmaniasis (VL) is one of the severest forms of parasite borne diseases worldwide with a mortality rate second only to malaria. Treatment of VL patients with currently available chemotherapeutic agents poses problems of large scale failure, toxicity, prolonged hospitalization time, high treatment cost and drug resistance. However, most of these problems can be overcome by the use of liposomal formulations of Amphotericin B (L-AmB). Of the two L-AmBs currently available in Indian market, AmBisome is imported and FUNGISOME is indigenous. Initially AmBisome remained exorbitantly costly and therefore inaccessible to most of the VL patients. However, with the launch of FUNGISOME in India, Gilead in agreement with WHO started a donation program of AmBisome in developing countries through a slashed price of US $18 per vial. The price reduction is, however, restricted to clinical trials thus eluding majority of the VL patients. In fact, India was not included in this program and AmBisome was sold in Indian market at prices higher than the WHO proposed price of US $18 per vial. FUNGISOME, on the other hand, produced consistently good results against VL both clinically and experimentally. In the context of unavailability and price anomaly of AmBisome, successful emergence of FUNGISOME could mark it as the major L-AmB against VL.

  19. Monitoring of Lutzomyia longipalpis Lutz & Neiva, 1912 in an area of intense transmission of visceral leishmaniasis in Rio Grande do Norte, Northeast Brazil.

    Science.gov (United States)

    Amóra, Sthenia Santos Albano; Bevilaqua, Claudia Maria Leal; Dias, Edmilson de Castro; Feijó, Francisco Marlon Carneiro; Oliveira, Paula Gabriela Melo de; Peixoto, Gislayne Christianne Xavier; Alves, Nilza Dutra; Oliveira, Lorena Mayana Beserra de; Macedo, Iara Térsia Freitas

    2010-01-01

    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 temperature, relative humidity and rainfall did not show a significant influence on population density. However, there were seasonal differences: approximately 70% of sand flies were captured during the rainy season (p < 0.05). The predominant species, L. longipalpis, is present in substantial number, representing a public health risk. Therefore, because of higher prevalence during the rainy season, we recommend intensified VL control measures before and during this season to reduce the risk of disease transmission.

  20. Phlebotomine sand flies (Diptera: Psychodidae) in the municipality of Várzea Grande: an area of transmission of visceral leishmaniasis in the state of Mato Grosso, Brazil.

    Science.gov (United States)

    Missawa, Nanci Akemi; Dias, Edelberto Santos

    2007-12-01

    Visceral leishmaniasis (VL) has been naturally transmitted in periurban areas due to the emergence and reemergence of its vectors in such areas. Aimed to further knowledge on ecological aspects affecting the occurrence of phlebotomine sand flies in VL transmission areas in the municipality of Várzea Grande, state of Mato Grosso (MT), Brazil, sand fly captures were carried out. Monthly collections of sand flies were undertaken with CDC light-traps, which were left in both intradomiciliary and peridomiciliary areas of ten residences during four consecutive days between January 2004 and June 2006. Twenty-two species of genus Lutzomyia and one of Brumptomyia were captured. The most abundant species was Lutzomyia longipalpis (65.23%), followed by L. evandroi (16.26%), L. lenti (7.69%), L. whitmani (4.92%), L. sallesi (2.34%) and L. termitophila (1.32%). The highest density of the main VL vector, L. longipalpis, was found in peridomiciliary areas, mostly males. No significant correlation was found between environment (temperature, air relative humidity and rain fall) and phlebotomine density; although a slight increase in sand fly density has been observed in the period following rainfalls, particularly L. longipalpis. No correlation was observed between distribution and density of L. longipalpis, prevalence of human VL cases and the presence of serologically positive dogs. The presence of infected dogs, increased vector density, susceptibility rate and interruption of epidemiological surveillance may raise the risk of VL transmission to man in Várzea Grande.

  1. Predicting the geographic distribution of Lutzomyia longipalpis (Diptera: Psychodidae and visceral leishmaniasis in the state of Mato Grosso do Sul, Brazil

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    Paulo Silva de Almeida

    2013-12-01

    Full Text Available To understand the geographic distribution of visceral leishmaniasis (VL in the state of Mato Grosso do Sul (MS, Brazil, both the climatic niches of Lutzomyia longipalpis and VL cases were analysed. Distributional data were obtained from 55 of the 79 counties of MS between 2003-2012. Ecological niche models (ENM of Lu. longipalpis and VL cases were produced using the maximum entropy algorithm based on eight climatic variables. Lu. longipalpis showed a wide distribution in MS. The highest climatic suitability for Lu. longipalpis was observed in southern MS. Temperature seasonality and annual mean precipitation were the variables that most influenced these models. Two areas of high climatic suitability for the occurrence of VL cases were predicted: one near Aquidauana and another encompassing several municipalities in the southeast region of MS. As expected, a large overlap between the models for Lu. longipalpis and VL cases was detected. Northern and northwestern areas of MS were suitable for the occurrence of cases, but did not show high climatic suitability for Lu. longipalpis . ENM of vectors and human cases provided a greater understanding of the geographic distribution of VL in MS, which can be applied to the development of future surveillance strategies.

  2. Predicting the geographic distribution of Lutzomyia longipalpis (Diptera: Psychodidae) and visceral leishmaniasis in the state of Mato Grosso do Sul, Brazil.

    Science.gov (United States)

    Almeida, Paulo Silva de; Sciamarelli, Alan; Batista, Paulo Mira; Ferreira, Ademar Dimas; Nascimento, João; Raizer, Josué; Andrade Filho, José Dilermando; Gurgel-Gonçalves, Rodrigo

    2013-12-01

    To understand the geographic distribution of visceral leishmaniasis (VL) in the state of Mato Grosso do Sul (MS), Brazil, both the climatic niches of Lutzomyia longipalpis and VL cases were analysed. Distributional data were obtained from 55 of the 79 counties of MS between 2003-2012. Ecological niche models (ENM) of Lu. longipalpis and VL cases were produced using the maximum entropy algorithm based on eight climatic variables. Lu. longipalpis showed a wide distribution in MS. The highest climatic suitability for Lu. longipalpis was observed in southern MS. Temperature seasonality and annual mean precipitation were the variables that most influenced these models. Two areas of high climatic suitability for the occurrence of VL cases were predicted: one near Aquidauana and another encompassing several municipalities in the southeast region of MS. As expected, a large overlap between the models for Lu. longipalpis and VL cases was detected. Northern and northwestern areas of MS were suitable for the occurrence of cases, but did not show high climatic suitability for Lu. longipalpis. ENM of vectors and human cases provided a greater understanding of the geographic distribution of VL in MS, which can be applied to the development of future surveillance strategies.

  3. Phlebotomine sand flies (Diptera: Psychodidae in the municipality of Várzea Grande: an area of transmission of visceral leishmaniasis in the state of Mato Grosso, Brazil

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    Nanci Akemi Missawa

    2007-12-01

    Full Text Available Visceral leishmaniasis (VL has been naturally transmitted in periurban areas due to the emergence and reemergence of its vectors in such areas. Aimed to further knowledge on ecological aspects affecting the occurrence of phlebotomine sand flies in VL transmission areas in the municipality of Várzea Grande, state of Mato Grosso (MT, Brazil, sand fly captures were carried out. Monthly collections of sand flies were undertaken with CDC light-traps, which were left in both intradomiciliary and peridomiciliary areas of ten residences during four consecutive days between January 2004 and June 2006. Twenty-two species of genus Lutzomyia and one of Brumptomyia were captured. The most abundant species was Lutzomyia longipalpis (65.23%, followed by L. evandroi (16.26%, L. lenti (7.69%, L. whitmani (4.92%, L. sallesi (2.34% and L. termitophila (1.32%. The highest density of the main VL vector, L. longipalpis, was found in peridomiciliary areas, mostly males. No significant correlation was found between environment (temperature, air relative humidity and rain fall and phlebotomine density; although a slight increase in sand fly density has been observed in the period following rainfalls, particularly L. longipalpis. No correlation was observed between distribution and density of L. longipalpis, prevalence of human VL cases and the presence of serologically positive dogs. The presence of infected dogs, increased vector density, susceptibility rate and interruption of epidemiological surveillance may raise the risk of VL transmission to man in Várzea Grande.

  4. Molecular detection of infection homogeneity and impact of miltefosine treatment in a Syrian golden hamster model of Leishmania donovani and L. infantum visceral leishmaniasis.

    Science.gov (United States)

    Eberhardt, Eline; Mondelaers, Annelies; Hendrickx, Sarah; Van den Kerkhof, Magali; Maes, Louis; Caljon, Guy

    2016-10-01

    Control of visceral leishmaniasis caused by Leishmania infantum and Leishmania donovani primarily relies on chemotherapy using an increasingly compromised repertoire of antileishmanial compounds. For evaluation of novel drugs, the Syrian golden hamster is considered as a clinically relevant laboratory model. In this study, two molecular parasite detection assays were developed targeting cathepsin-like cysteine protease B (CPB) DNA and 18S rRNA to achieve absolute amastigote quantification in the major target organs liver and spleen. Both quantitative PCR (qPCR) techniques showed excellent agreement with a strong correlation with the conventional microscopic reading of Giemsa-stained tissue smears. Using multiple single tissue pieces and all three detection methods, we confirmed homogeneity of infection in liver and spleen and the robustness of extrapolating whole organ burdens from a small single tissue piece. Comparison of pre- and post-treatment burdens in infected hamsters using the three detection methods consistently revealed a stronger parasite reduction in the spleen compared to the liver, indicating an organ-dependent clearance efficacy for miltefosine. In conclusion, this study in the hamster demonstrated high homogeneity of infection in liver and spleen and advocates the use of molecular detection methods for assessment of low (post-treatment) tissue burdens.

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

    DEFF Research Database (Denmark)

    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...... by interleukin-4 (IL-4)-producing Th2 cells, or cure may result by Th1 cells secreting gamma interferon (IFN-gamma). The present study examined the potential of human T cells to generate Th1 or Th2 responses to L. donovani. The profiles of IFN-gamma, IL-4, and lymphotoxin secretion after antigen stimulation were...... analyzed in a panel of L. donovani-reactive CD4+ human T-cell clones generated from individuals who had recovered from VL after antimonial treatment. Two of the T-cell clones produced large amounts of IL-4 without production of IFN-gamma, seven clones produced both IFN-gamma and IL-4, and eight produced...

  6. Laryngeal Leishmaniasis

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    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.

  7. Leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.

    Science.gov (United States)

    Lakshmi, Bhavana Sethu; Wang, Ruobing; Madhubala, Rentala

    2014-06-24

    Leishmaniasis is a neglected tropical disease caused by Leishmania species. It is a major health concern affecting 88 countries and threatening 350 million people globally. Unfortunately, there are no vaccines and there are limitations associated with the current therapeutic regimens for leishmaniasis. The emerging cases of drug-resistance further aggravate the situation, demanding rapid drug and vaccine development. The genome sequence of Leishmania, provides access to novel genes that hold potential as chemotherapeutic targets or vaccine candidates. In this study, we selected 19 antigenic genes from about 8000 common Leishmania genes based on the Leishmania major and Leishmania infantum genome information available in the pathogen databases. Potential vaccine candidates thus identified were screened using an in vitro high throughput immunological platform developed in the laboratory. Four candidate genes coding for tuzin, flagellar glycoprotein-like protein (FGP), phospholipase A1-like protein (PLA1) and potassium voltage-gated channel protein (K VOLT) showed a predominant protective Th1 response over disease exacerbating Th2. We report the immunogenic properties and protective efficacy of one of the four antigens, tuzin, as a DNA vaccine against Leishmania donovani challenge. Our results show that administration of tuzin DNA protected BALB/c mice against L. donovani challenge and that protective immunity was associated with higher levels of IFN-γ and IL-12 production in comparison to IL-4 and IL-10. Our study presents a simple approach to rapidly identify potential vaccine candidates using the exhaustive information stored in the genome and an in vitro high-throughput immunological platform.

  8. Presence of Circulating Levels of Interferon-g, Interleukin-10 and Tumor Necrosis Factor-a in Patients with Visceral Leishmaniasis

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    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

  9. 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

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    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.

  10. Cystatin cures visceral leishmaniasis by NF-κB-mediated proinflammatory response through co-ordination of TLR/MyD88 signaling with p105-Tpl2-ERK pathway.

    Science.gov (United States)

    Kar, Susanta; Ukil, Anindita; Das, Pijush K

    2011-01-01

    Cystatin could completely cure experimental visceral leishmaniasis by switching the differentiation of Th2 cells to Th1 type, as well as upregulating NO, and activation of NF-κB played a major role in these processes. Analysis of upstream signaling events revealed that TLR 2/4-mediated MyD88-dependent participation of IL-1R-activated kinase (IRAK)1, TNF receptor-associated factor (TRAF)6 and TGFβ-activated kinase (TAK)1 is essential to induce cystatin-mediated IκB kinase (IKK)/NF-κB activation in macrophages. Cystatin plus IFN-γ activated the IKK complex to induce phosphorylation-mediated degradation of p105, the physiological partner and inhibitor of the MEK kinase, tumor progression locus 2 (Tpl-2). Consequently, Tpl-2 was liberated from p105, thereby stimulating activation of the MEK/ERK MAPK cascade. Cystatin plus IFN-γ-induced IKK-β post-transcriptionally modified p65/RelA subunit of NF-κB by dual phosphorylation in infected phagocytic cells. IKK induced the phosphorylation of p65 directly on Ser-536 residue whereas phosphorylation on Ser 276 residue was by sequential activation of Tpl-2/MEK/ERK/MSK1. Collectively, the present study indicates that cystatin plus IFN-γ-induced MyD88 signaling may bifurcate at the level of IKK, leading to a divergent pathway regulating NF-κB activation by IκBα phosphorylation and by p65 transactivation through Tpl-2/MEK/ERK/MSK1.

  11. Usefulness of the rK39-Immunochromatographic Test, Direct Agglutination Test, and Leishmanin Skin Test for Detecting Asymptomatic Leishmania Infection in Children in a New Visceral Leishmaniasis Focus in Amhara State, Ethiopia

    Science.gov (United States)

    Gadisa, Endalamaw; Custodio, Estefanía; Cañavate, Carmen; Sordo, Luis; Abebe, Zelalem; Nieto, Javier; Chicharro, Carmen; Aseffa, Abraham; Yamuah, Lawrence; Engers, Howard; Moreno, Javier; Cruz, Israel

    2012-01-01

    In areas where visceral leishmaniasis is anthroponotic, asymptomatically infected patients may play a role in transmission. Additionally, the number of asymptomatic patients in a disease-endemic area will also provide information on transmission dynamics. Libo Kemkem and Fogera districts (Amhara State, Ethiopia) are now considered newly established areas to which visceral leishmaniasis is endemic. In selected villages in these districts, we conducted a study to assess the usefulness of different approaches to estimate the asymptomatic infection rate. Of 605 participants, the rK39 immunochromatographic test was able to detect asymptomatic infection in 1.5% (9 of 605), direct agglutination test in 5.3% (32 of 605), and leishmanin skin test in 5.6% (33 of 589); the combined use of serologic methods and leishmanin skin test enabled detecting asymptomatic infection in 10.1% (61 of 605). We conclude that the best option to detect asymptomatic infection in this new visceral leishmaniasis–endemic focus is the combined use of the direct agglutination test and the leishmanin skin test. PMID:22556076

  12. Leishmaniose visceral: estudo de flebotomíneos e infecção canina em Montes Claros, Minas Gerais Visceral leishmaniasis: a study on phlebotomine sand flies and canine infection in Montes Claros, State of Minas Gerais

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    Érika Michalsky Monteiro

    2005-04-01

    Full Text Available A leishmaniose visceral no Brasil estava inicialmente associada a áreas rurais, mas devido às diversas alterações no ambiente como, desmatamentos, urbanização e intenso processo migratório, ocorreu a expansão das áreas endêmicas, levando à urbanização da doença, principalmente nas regiões Sudeste e Centro Oeste do país. No município de Montes Claros, situado ao norte de Minas Gerais, foi feito um estudo para verificação da situação da LV. No ano de 2002 foi realizado inquérito sorológico canino e no período de setembro de 2002 a agosto de 2003 foi feito levantamento entomológico, utilizando armadilhas luminosas de CDC. A prevalência da LV canina apresentou taxa média de infecção em torno de 5%. A fauna de flebotomíneos estimada foi de 16 espécies, totalizando 1043 exemplares. Lutzomyia longipalpis foi a espécie predominante com 74%, o que sugere a sua participação na transmissão de LV em Montes Claros.Visceral leishmaniasis in Brazil was initially associated with rural areas. However, due to several environmental modifications such as deforestation, urbanization and intense migratory processes, there has been an expansion of endemic areas, leading to urbanization of the disease, mainly in the central and northeastern regions of Brazil. In the municipality of Montes Claros, located in the north of the state of Minas Gerais, an epidemiological survey on VL was carried out. A canine serological inquiry was carried out in 2002 and an entomological survey, using luminous CDC traps, was performed from September 2002 to August 2003. Canine VL prevalence showed an average infection rate of approximately 5%. An estimated 16 species comprised the phlebotomine sand fly fauna, based on a total of 1043 specimens. The predominant species was Lutzomyia longipalpis with a rate of 74%, suggesting its participation in the transmission of VL in the municipality of Montes Claros.

  13. Compo