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Sample records for visceral leishmaniasis relapse

  1. Visceral Leishmaniasis

    Science.gov (United States)

    2011-06-01

    Autoclaved Leishmania major vaccine for prevention of visceral leishmaniasis: a randomised, double-blind, BCG -controlled trial in Sudan. Lancet...nitric oxide killing. These properties of sandfly saliva are the focus of current research on an antileishmania vaccine .11 At the site of inoculation...these campaigns, incidence has returned to high levels. No VL vaccine is currently licensed or commercially available. A variety of vaccine

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

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    E. Jeziorski

    2015-04-01

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

  3. Immunity to Visceral Leishmaniasis

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    Ali, Nahid; Mekuria, Asrat Hailu; Requena, José María; Engwerda, Christian

    2012-01-01

    Leishmaniasis is a major vector-borne parasitic disease affecting 12 million people worldwide. With a broad range of clinical manifestations, ranging from self-healing skin ulcers to disfiguring mucosal lesions to life-threatening infections of visceral organs (liver and spleen), the disease has become a serious human health issue, particularly in developing countries. Among all of its forms, visceral leishmaniasis (VL, also known as kala-azar), caused by the Leishmania donovani complex (i.e....

  4. 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.

  5. Immunobiology of visceral leishmaniasis

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    Susanne eNylén

    2012-08-01

    Full Text Available Visceral leishmaniasis (VL, commonly known as kala-azar, is caused by Leishmania donovani and Leishmania infantum (Leishmania chagasi in the Americas. These Leishmania species infect macrophages throughout the viscera, and parasites are typically found in the spleen, liver and bone marrow. Patients with active disease typically exhibit marked immunosuppression, lack reactivity to the Leishmania skin test (LST, a delayed type hypersensitivity test, and their peripheral blood mononuclear cells (PBMC fail to respond when stimulated with leishmanial antigens in vitro. However, most people infected with visceralizing species of Leishmania never develop disease. Understanding immune failure and the underlying immune mechanism that lead to disease as well as control of infection are key questions for research in this field. In this review we discuss immunological events described in human and experimental VL and how these can affect the outcome of infection.

  6. Visceral leishmaniasis in Brazil

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    Mary Marcondes

    2013-10-01

    Full Text Available Visceral leishmaniasis (VL is among the most important vector-borne diseases that occur in Brazil, mainly due to its zoonotic nature. It is currently present in almost all Brazilian territory, and its control is a challenge both for veterinarians and for public health officials. The etiologic agent is Leishmania infantum (syn chagasi, and the main vector in Brazil is Lutzomyia longipalpis. Of all animals identified as reservoirs of VL, the dog is considered the most important domestic reservoir. Although the disease has already been identified in cats, the epidemiological role of this animal species is still unclear. This article presents a brief review of the epidemiological situation of the disease, its mode of transmission, clinical features in dogs and cats as well as possible risk factors associated with the occurrence of the disease in Brazil.

  7. [Visceral leishmaniasis: an update].

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    Faucher, B; Piarroux, R

    2011-09-01

    During the last decade, visceral leishmaniasis has been reconsidered in its epidemiology and strategies for diagnosis, treatment and prevention. This vectorial disease, responsible for more than 50,000 deaths each year across India, East Africa, South America, the Mediterranean area, Central Asia and China, is currently spreading over new territories. This formerly rural disease has even reached cities in South America. This spreading is caused by environmental changes due to global warming or human activity, and by the movement of workers and refugees. As a consequence, the burden of HIV/Leishmania coinfection is increasing in many developing countries even though effective antiretroviral therapy has led to a marked decrease in its incidence in Europe. The disease is now handled differently than it was 10 years ago: PCR has become the most accurate tool for diagnosis and follow-up in developed countries, and field diagnostic tools have been developed (antigenuria, rK39 dipstick). While resistance to antimoniate has appeared in India and Europe, new therapies have been evaluated such as miltefosine, the first oral therapy, or short treatment with liposomal amphotericin B. In France, liposomal amphotericin B has supplanted antimoniate meglumine because of better tolerance and shorter hospitalization duration. Protecting dogs through immunization or collars impregnated with deltamethrin proved effective to prevent zoonotic leishmaniasis due to Leishmania infantum. Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  8. Immunity and immunosuppression in experimental visceral leishmaniasis

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    Goto H; Lindoso J.A.L.

    2004-01-01

    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 viscera...

  9. Visceral leishmaniasis: an update of laboratory diagnosis

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    Zineb Tlamcani

    2016-07-01

    Full Text Available Visceral leishmaniasis, is an infection due to obligate intracellular protozoa of the genus Leishmania. There exist two varieties of visceral leishmaniasis, that vary in their transmission aspects: zoonotic visceral leishmaniasis and anthroponotic visceral leishmaniasis. Their clinical features are comparable with sevral differences. Laboratory diagnosis of visceral leishmaniasis consists of microscopic observation of parasite, culture from appropriate samples, detection of antigen, serological tests, and identification of parasite DNA. In this review, we will discuss the different techniques of diagnosis and the interet of the recent methods such as rapid diagnostic test and direct agglutination test.

  10. 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

  11. IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test.

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    Tapan Bhattacharyya

    2014-10-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL, caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care. METHODOLOGY/PRINCIPAL FINDINGS: All IgG subclass and IgG isotype antibody levels were determined using unpaired serum samples from Indian and Sudanese patients with differing clinical status of VL, which included pre-treatment active VL, post-treatment cured, post-treatment relapsed, and post kala-azar dermal leishmaniasis (PKDL, as well as seropositive (DAT and/or rK39 endemic healthy controls (EHCs and seronegative EHCs. L. donovani antigen-specific IgG1 levels were significantly elevated in relapsed versus cured VL patients (p<0.0001. Using paired Indian VL sera, consistent with the known IgG1 half-life, IgG1 levels had not decreased significantly at day 30 after the start of treatment (p = 0.8304, but were dramatically decreased by 6 months compared to day 0 (p = 0.0032 or day 15 (p<0.0001 after start of treatment. Similarly, Sudanese sera taken soon after treatment did not show a significant change in the IgG1 levels (p = 0.3939. Two prototype lateral flow immunochromatographic rapid diagnostic tests (RDTs were developed to detect IgG1 levels following VL treatment: more than 80% of the relapsed VL patients were IgG1 positive; at least 80% of the cured VL patients were IgG1 negative (p<0.0001. CONCLUSIONS/SIGNIFICANCE: Six months after treatment of active VL, elevated levels of specific IgG1 were associated with treatment failure and relapse, whereas no IgG1 or low levels were detected in cured VL patients. A lateral flow RDT was successfully developed to detect anti-Leishmania IgG1 as a potential biomarker of post

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

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

    2016-01-01

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

  13. [Visceral leishmaniasis. Pediatric case report].

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    Gomila H, Andrés; Vanzo, Carolina; Garnero, Analía; Peruzzo, Luisina; Badalotti, Mónica

    2017-08-01

    La leishmaniasis es una enfermedad causada por parásitos obligados intracelulares pertenecientes al género Leishmania y que reconoce tres formas clínicas principales: cutánea, visceral y mucocutánea. Es una patología del grupo de las "enfermedades desatendidas". Es la única enfermedad tropical transmitida a través de vectores que se ha mantenido endémica por décadas en el sur de Europa. La leishmaniasis visceral representa la forma más grave. Se caracteriza por fiebre, pérdida de peso, anemia y hepatoesplenomegalia. Su período de incubación oscila entre 2 semanas y 18 meses. La leishmaniasis se considera una enfermedad reemergente a nivel mundial. Algunos de los factores que favorecen esta situación son los cambios en las condiciones climáticas, migraciones y urbanizaciones deficitarias en saneamiento ambiental. Se presenta el caso de un niño europeo que estaba vacacionando en Córdoba y fue derivado a nuestro Hospital por fiebre y pancitopenia, lo que generó un abordaje multidisciplinario con resolución clínica favorable. Sociedad Argentina de Pediatría.

  14. Therapeutic options for visceral leishmaniasis.

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    Monge-Maillo, Begoña; López-Vélez, Rogelio

    2013-11-01

    Visceral leishmaniasis (VL), also known as Kala-Azar, is a disseminated protozoal infection caused principally by Leishmania donovani and Leishmania infantum (known as Leishmania chagasi in South America). The therapeutic options for VL are diverse and depend on different factors, such as the geographical area of the infection, development of resistance to habitual treatments, HIV co-infection, malnourishment and other concomitant infections. This article provides an exhaustive review of the literature regarding studies published on the treatment of VL, and gives therapeutic recommendations stratified according to their level of evidence, the species of Leishmania implicated and the geographical location of the infection.

  15. Drug Resistance in Visceral Leishmaniasis

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    Helena C. Maltezou

    2010-01-01

    Full Text Available Visceral leishmaniasis remains a public health problem worldwide. This illness was included by the World Health Organization in the list of neglected tropical diseases targeted for elimination by 2015. The widespread emergence of resistance to pentavalent antimonials in India where half cases occur globally and the unavailability of a vaccine in clinical use constitute major obstacles in achieving this goal. The last decade new antileishmanials became available, including the oral agent miltefosine. However, in poor endemic countries their wide use was curtailed because of the high costs, and also due to concerns of toxicity and emergence of resistance. Various mechanisms of antileishmanial resistance were identified recently in field isolates. Their elucidation will boost the design of new drugs and the molecular surveillance of resistance. Combination regimens should be evaluated in large trials. Overall, the development of antileishmanials has been generally slow; new drugs are needed. In order to control visceral leishmaniasis worldwide, treatment advances should become affordable in the poorest countries, where they are needed most.

  16. [A case report of visceral leishmaniasis].

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    Popov, G; Andreeva, N; Georgiev, A; Kuzmanova, E

    1991-01-01

    A brief review of the spread of visceral leishmaniasis in Bulgaria and data about the disease are presented. A case of probably nonautochtonous form of visceral leishmaniasis is described. The clinical evolution of the disease is followed up and the large number of examinations which were carried out for the etiological diagnosis are presented. The diagnosis is based on the characteristic clinical symptoms, epidemiological history, positive serologic tests but with a negative myelogram. The diagnosis was proved ex juvantibus by the antimony treatment and the full recovery of the patient. This is the first case of visceral leishmaniasis in the 40 year history of the hospital.

  17. Visceral Leishmaniasis Treated with Antimonials/Paromomycin followed by Itraconazole/Miltefosine after Standard Therapy Failures in a Human Immunodeficiency Virus–Infected Patient

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    Barragán, Patricia; López-Velez, Rogelio; Olmo, Montserrat; Podzamczer, Daniel

    2010-01-01

    Visceral leishmaniasis is an opportunistic infection that affects human immunodeficiency virus–infected persons in leishmaniasis-endemic areas. The standard treatment may not be effective and relapses are common. We report the case of a human immunodeficiency virus-1–infected patient who had several relapses of visceral leishmaniasis after treatment with standard therapies and responded to a combined therapy.

  18. Visceral leishmaniasis complicating systemic lupus erythematosus

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    Wallis, P. J. W.; Clark, C. J. M.

    1983-01-01

    Active systemic lupus erythematosus in a 32-year-old Chinese woman was successfully controlled by plasmapheresis and steroids. However, occult visceral leishmaniasis was uncovered during therapy and responded to appropriate treatment.

  19. 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.

  20. [Treatment of visceral leishmaniasis in children].

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    Minodier, P; Noël, G; Blanc, P; Uters, M; Retornaz, K; Garnier, J M

    2007-02-01

    Visceral Leishmania infantum leishmaniasis is endemic in the south of France. For many years the mainstay for treatment of infected children was pentavalent antimony: meglumine antimoniate (Glucantime) or sodium stibogluconate (Pentostam). However these drugs are poorly tolerated and resistance similar to that observed in the treatment of Indian visceral Leishmania donovani leishmaniasis has been reported. Currently liposomal amphotericin B is being used instead of antimony for treatment of visceral leishmaniasis in children in France. In addition to being well tolerated, liposomal amphotericin B is almost 100% effective. It can be administered in six intravenous injections of 3-4 mg/kg each (days 1 to 5 then day 10). A two-day protocol (10 mg/kg/d) that would reduce overall cost by shortening the duration of hospitalization is now being studied. Another oral drug, i.e., miltefosine, has been successfully used for treatment of visceral leishmaniasis in India. However it has not been evaluated for treatment of Mediterranean visceral leishmaniasis.

  1. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Management of visceral leishmaniasis: Indian perspective

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    Agrawal S; Rai M; Sundar S

    2005-01-01

    Diagnosis and treatment of Indian visceral leishmaniasis (VL) is extremely unsatisfactory. For diagnosis, demonstration of parasites in splenic/marrow smears remains the gold standard, though k39 rapid strip test is a useful method in regions where access to parasite demonstration is difficult. pentavalent antimony remains the mainstay for the treatment of all forms of leishmaniasis globally; however, development of large-scale antimony resistance in Bihar has necessitated search for alternat...

  3. Visceral Leishmaniasis in Rural Bihar, India

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    Singh, Shri Prakash; Malaviya, Paritosh; Picado, Albert; Gidwani, Kamlesh; Singh, Rudra Pratap; Menten, Joris; Boelaert, Marleen; Sundar, Shyam

    2012-01-01

    To identify factors associated with incidence of visceral leishmaniasis (VL), we surveyed 13,416 households in Bihar State, India. VL was associated with socioeconomic status, type of housing, and belonging to the Musahar caste. Annual coverage of indoor residual insecticide spraying was 12%. Increasing such spraying can greatly contribute to VL control. PMID:23017164

  4. Immunity to visceral leishmaniasis: implications for immunotherapy.

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    Khadem, Forough; Uzonna, Jude E

    2014-01-01

    Visceral leishmaniasis, caused by Leishmania donovani, L. infantum (syn. Leishmania chagasi), is a globally widespread disease with a burden of about 400,000 new infections reported annually. It is the most dangerous form of human leishmaniasis in terms of mortality and morbidity and is spreading to several nonendemic areas because of migration, global traveling and military conflicts. The emergence of Leishmania-HIV co-infection and increased prevalence of drug-resistant strains have worsened the impact of the disease. The traditional low-cost drugs are often toxic with several adverse effects, highlighting the need for development of new therapeutic and prophylactic strategies. Therefore, a detailed understanding of mechanisms of protective immunity is extremely important in order to develop new therapeutics in the form of vaccines or immunotherapies. This review gives an overview of visceral leishmaniasis, with particular emphasis on the innate and adaptive immune responses, vaccine and vaccination strategies and their potentials for immunotherapy against the disease.

  5. Endemic transmission of visceral leishmaniasis in Bhutan.

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    Yangzom, Thinley; Cruz, Israel; Bern, Caryn; Argaw, Daniel; den Boer, Margriet; Vélez, Iván Dario; Bhattacharya, Sujit K; Molina, Ricardo; Alvar, Jorge

    2012-12-01

    Visceral leishmaniasis was first reported in Bhutan in 2006. We conducted studies of the parasite, possible vectors and reservoirs, and leishmanin skin test and risk factor surveys in three villages. Nineteen cases were reported from seven districts. Parasite typing yielded two novel microsatellite sequences, both related to Indian L. donovani. In one case village, 40 (18.5%) of 216 participants had positive leishmanin skin test results, compared with 3 (4.2%) of 72 in the other case village and 0 of 108 in the control village. Positive results were strongly associated with the village and increasing age. None of the tested dogs were infected. Eighteen sand flies were collected, 13 Phlebotomus species and 5 Sergentomyia species; polymerase chain reaction for leishmanial DNA was negative. This assessment suggests that endemic visceral leishmaniasis transmission has occurred in diverse locations in Bhutan. Surveillance, case investigations, and further parasite, vector, and reservoir studies are needed. The potential protective impact of bed nets should be evaluated.

  6. Genetically modified organisms and visceral leishmaniasis.

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    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.

  7. American visceral Leishmaniasis: a case report

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    H. Langoni

    2005-09-01

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

  8. Autochthonous Outbreak and Expansion of Canine Visceral Leishmaniasis, Uruguay

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    Satragno, Dinora; Faral-Tello, Paula; Canneva, Bruno; Verger, Lorenzo; Lozano, Alejandra; Vitale, Edgardo; Greif, Gonzalo; Soto, Carlos

    2017-01-01

    We report an outbreak of canine visceral leishmaniasis in Uruguay. Blood specimens from 11/45 dogs tested positive for Leishmania spp. Specimens of Lutzomyia longipalpis sand flies were captured; typing revealed Leishmania infantum. Our findings document an expansion of visceral leishmaniasis to southern South America and risk for vectorborne transmission to humans. PMID:28221113

  9. Visceral leishmaniasis and leishmaniasis-HIV coinfection: comparative study

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    João Victor Soares Coriolano Coutinho

    Full Text Available Abstract INTRODUCTION: This study aimed to draw clinical and epidemiological comparisons between visceral leishmaniasis (VL and VL associated with human immunodeficiency virus (HIV infection. METHOD: Retrospective study. RESULTS: Of 473 cases of VL, 5.5% were coinfected with HIV. The highest proportion of cases of both VL and VL/HIV were found among men. A higher proportion of VL cases was seen in children aged 0-10 years, whereas coinfection was more common in those aged 18-50 years. CONCLUSIONS: VL/HIV coinfected patients presented slightly differently to and had a higher mortality rate than those with VL only.

  10. Immune Regulation during Chronic Visceral Leishmaniasis

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

    2014-01-01

    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. PMID:25010815

  11. Determinants for the development of visceral leishmaniasis disease.

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    Laura-Isobel McCall

    2013-01-01

    Full Text Available Leishmaniasis is a vector-borne neglected tropical disease associated with a spectrum of clinical manifestations, ranging from self-healing cutaneous lesions to fatal visceral infections. Among the most important questions in Leishmania research is why some species like L. donovani infect visceral organs, whereas other species like L. major remain in the skin. The determinants of visceral leishmaniasis are still poorly understood, although genomic, immunologic, and animal models are beginning to provide important insight into this disease. In this review, we discuss the vector, host, and pathogen factors that mediate the development of visceral leishmaniasis. We examine the progression of the parasite from the initial site of sand fly bite to the visceral organs and its ability to survive there. The identification of visceral disease determinants is required to understand disease evolution, to understand visceral organ survival mechanisms, and potentially to develop better interventions for this largely neglected disease.

  12. Genetically Modified Organisms and Visceral Leishmaniasis

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    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.

  13. 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.

  14. 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....

  15. Visceral leishmaniasis and HIV coinfection in the Mediterranean region.

    Directory of Open Access Journals (Sweden)

    Begoña Monge-Maillo

    2014-08-01

    Full Text Available Visceral leishmaniasis is hypoendemic in Mediterranean countries, where it is caused by the flagellate protozoan Leishmania infantum. VL cases in this area account for 5%-6% of the global burden. Cases of Leishmania/HIV coinfection have been reported in the Mediterranean region, mainly in France, Italy, Portugal, and Spain. Since highly active antiretroviral therapy was introduced in 1997, a marked decrease in the number of coinfected cases in this region has been reported. The development of new diagnostic methods to accurately identify level of parasitemia and the risk of relapse is one of the main challenges in improving the treatment of coinfected patients. Clinical trials in the Mediterranean region are needed to determine the most adequate therapeutic options for Leishmania/HIV patients as well as the indications and regimes for secondary prophylaxis. This article reviews the epidemiological, diagnostic, clinical, and therapeutic aspects of Leishmania/HIV coinfection in the Mediterranean region.

  16. Leishmaniasis in Turkey: Visceral and cutaneous leishmaniasis caused by Leishmania donovani in Turkey

    NARCIS (Netherlands)

    Özbilgin, Ahmet; Harman, Mehmet; Karakuş, Mehmet; Bart, Aldert; Töz, Seray; Kurt, Özgür; Çavuş, İbrahim; Polat, Erdal; Gündüz, Cumhur; van Gool, Tom; Özbel, Yusuf

    2017-01-01

    In Turkey, the main causative agents are Leishmania tropica (L. tropica) and Leishmania infantum (L. infantum) for cutaneous leishmaniasis (CL) and L. infantum for visceral leishmaniasis (VL). In this study, we investigated leishmaniasis cases caused by L. donovani and established animal models for

  17. Perceived quality of life among Visceral Leishmaniasis and HIV coinfected migrant male-workers in Northwest Ethiopia: a qualitative study.

    Science.gov (United States)

    Alemayehu, Mekuriaw; Wubshet, Mamo; Mesfin, Nebiyu; Gebayehu, Abebaw

    2017-02-16

    There is paucity of data on quality of life as a dimension of treatment outcome among Visceral Leishmaniasis and HIV coinfected patients. This study sought to explore perceived quality of life among Visceral Leishmaniasis and HIV coinfected male migrant workers in Northwest Ethiopia. Twenty Visceral Leishmaniasis and HIV coinfected study participants took part in the in-depth interviews at Visceral Leishmaniasis and HIV treatment centers. Ten participants were on antiretroviral treatment (ART) and the remaining 10 have not yet started ART. All interviews were recorded, transcribed and translated for analysis. Data were analyzed by qualitative content analysis using Open Code software version 3.4. Participants reported on four aspects of quality of life: liveability of the environment, utility of life, life ability of a person and appreciation of life. Respondents living environment, therapeutic side effects of Visceral Leishmaniasis drugs, poverty and stigma negatively affected their quality of life. On the contrary, good treatment response and financial security were reported to positively affect their quality of life. Challenges related to the living environment, financial limitations and sub-optimal response of Visceral Leishmaniasis drug and relapse of Visceral Leishmaniasis disease are factors most negatively affecting the quality of life of Visceral Leishmaniasis and HIV coinfected patients. Micro-financing and other socio-economical support programs should be launched to assist the unemployed males migrating to Visceral Leishmaniasis endemic and relatively higher HIV prevalent areas to work as daily laborers. HIV prevention programs in HIV positive-living counseling programs should target such high risk migrant workers in the endemic areas.

  18. Visceral leishmaniasis in zoo and wildlife.

    Science.gov (United States)

    Souza, Tayse Domingues; Turchetti, Andréia Pereira; Fujiwara, Ricardo Toshio; Paixão, Tatiane Alves; Santos, Renato Lima

    2014-03-01

    Visceral leishmaniasis (VL) is an emerging zoonosis caused by Leishmania (Leishmania) infantum. Although the domestic dog is the main vertebrate host, many zoo and wild mammal species have been diagnosed with L. infantum infection, especially in endemic areas. There are many available diagnostic approaches, including serological, parasitological and molecular tests. Among wild animals, carnivores and primates are more often clinically affected, with some species, such as the bush dog (Speothos venaticus) being especially susceptible to development of clinical signs. There are also reports and research articles of VL in felids, rodents, and marsupials. This work aims to review the occurrence of VL in zoo and wildlife and raise awareness of its importance in the field of conservational veterinary medicine. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. [Visceral leishmaniasis without splenomegaly. A pediatric case report].

    Science.gov (United States)

    Leblanc, C; Nouar, D; Izri, A; Brun, S; Marty, P; Gaudelus, J; De Pontual, L

    2016-04-01

    Pediatric visceral leishmaniasis is caused by Leishmania infantum, a dog parasite transmitted to humans by the bite of the female phlebotomine sand fly. The well-known clinical triad is fever, pallor, and splenomegaly. A secondary macrophage activation syndrome (MAS) can complicate this infection, which is lethal when not treated. When MAS is observed without any explanation, a visceral leishmaniasis is highly recommended. We report a case of visceral leishmaniasis in a 21-month-old child complicated by a macrophage activation syndrome without splenomegaly. No immunodeficiency was diagnosed that could explain this unusual clinical condition. To our knowledge, this is the first case of visceral leishmaniasis without splenomegaly reported to date. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  20. Eugenol derived immunomodulatory molecules against visceral leishmaniasis.

    Science.gov (United States)

    Charan Raja, Mamilla R; Velappan, Anand Babu; Chellappan, Davidraj; Debnath, Joy; Kar Mahapatra, Santanu

    2017-10-20

    Visceral leishmaniasis (VL) is a life threatening infectious disease caused by Leishmania donovani. It leads to the severe immune suppression in the host defense system. Higher cytotoxicity, rigorous side effects and lower therapeutic indexes (TI) of current antileishmanial drugs have created a necessity to develop new molecules with better antileishmanial activity and high TI value. In this study, we have synthesized 36 derivatives of eugenol and screened them for their activity against promastigote and amastigote forms of L. donovani. Among the synthesized derivatives, comp.35 showed better antileishmanial activity against extra cellular promastigotes (IC50- 20.13 ± 0.91 μM) and intracellular amastigotes (EC50-4.25 ± 0.26 μM). The TI value (82.24 ± 3.77) was found to improve by 10-13 fold compared to Amphotericin B and Miltefosine respectively. Treatment with comp.35 (5 μg/ml) enhanced the nitric oxide (NO) generation, iNOS2 mRNA expression (∼8 folds increase) and decreased the arginase-1 activity (∼4 folds) in L. donovani infected peritoneal macrophages. Comp.35 had also increased the IL-12 (∼6 folds) and decreased the IL-10 (∼3 folds) mRNA expression and release in vitro. Results of in vivo studies revealed that comp.35 treatment at 25 mg/kg body weight efficiently cleared the hepatic and splenic parasite burden with enhanced Th1 response in L. donovani infected BALB/c mice. Hence, this study clearly represents comp.35, as an immunomodulatory molecule, can induce host protective immune response against visceral leishmaniasis through enhanced NO generation and Th1 response, which are essentials against this deadly disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Management of visceral leishmaniasis: Indian perspective.

    Science.gov (United States)

    Agrawal, S; Rai, M; Sundar, S

    2005-01-01

    Diagnosis and treatment of Indian visceral leishmaniasis (VL) is extremely unsatisfactory. For diagnosis, demonstration of parasites in splenic/marrow smears remains the gold standard, though k39 rapid strip test is a useful method in regions where access to parasite demonstration is difficult. pentavalent antimony remains the mainstay for the treatment of all forms of leishmaniasis globally; however, development of large-scale antimony resistance in Bihar has necessitated search for alternative drugs. Amphotericin B is the most effective, though toxic, drug for patients with refractory VL. Lipid formulations of amphotericin B, though safe and effective, are too expensive to be useful for poor patients of this region. These hold advantage as large quantity of the drug can safely be given over a short period of time, thus leading to a decrease in the hospital stay to a few days instead of several weeks. Oral miltefosine, an alkyl phospholipid, has recently been approved and marketed in India for the treatment of VL. Miltefosine cures 94% patients with VL if given in a daily dose of 50-100 mg for 28 days. Most common adverse events are mild vomiting and diarrhea. Paromomycin, an amino glycoside, is undergoing a pivotal phase-III clinical trial, and is likely to be approved and available to patients with VL at an affordable cost. To protect the already scarce inventory of antileishmanial drugs, it is time that combination chemotherapy is introduced for the treatment of VL in India.

  2. Management of visceral leishmaniasis: Indian perspective

    Directory of Open Access Journals (Sweden)

    Agrawal S

    2005-01-01

    Full Text Available Diagnosis and treatment of Indian visceral leishmaniasis (VL is extremely unsatisfactory. For diagnosis, demonstration of parasites in splenic/marrow smears remains the gold standard, though k39 rapid strip test is a useful method in regions where access to parasite demonstration is difficult. pentavalent antimony remains the mainstay for the treatment of all forms of leishmaniasis globally; however, development of large-scale antimony resistance in Bihar has necessitated search for alternative drugs. Amphotericin B is the most effective, though toxic, drug for patients with refractory VL. Lipid formulations of amphotericin B, though safe and effective, are too expensive to be useful for poor patients of this region. These hold advantage as large quantity of the drug can safely be given over a short period of time, thus leading to a decrease in the hospital stay to a few days instead of several weeks. Oral miltefosine, an alkyl phospholipid, has recently been approved and marketed in India for the treatment of VL. Miltefosine cures 94% patients with VL if given in a daily dose of 50-100 mg for 28 days. Most common adverse events are mild vomiting and diarrhea. Paromomycin, an amino glycoside, is undergoing a pivotal phase-III clinical trial, and is likely to be approved and available to patients with VL at an affordable cost. To protect the already scarce inventory of antileishmanial drugs, it is time that combination chemotherapy is introduced for the treatment of VL in India.

  3. Nanomedicines for Therapy of Visceral Leishmaniasis.

    Science.gov (United States)

    Want, Muzamil Yaqub; Yadav, Priya; Afrin, Farhat

    2016-03-01

    Visceral leishmaniasis (VL) or kala-azar is a vector borne infectious disease caused by the protozoan parasites of the genus Leishmania. VL is endemic in more than 85 countries with an estimated 0.2-0.5 million people at risk, causing high morbidity and mortality across the globe. In the absence of effective vaccines, treatment solely relies on chemotherapy and can be 100% fatal within two years, if left untreated. However, the present chemotherapeutics is limited by toxicity, non-compliance, location of parasites within the lysosomal vacuoles of macrophages, impairing the accession of many potential antileishmanial drugs, prolonged and cumbersome regimen that is unaffordable by rural population with alarming increase in unresponsiveness, complications of post kala-azar dermal leishmaniasis (PKDL) and HIV co-infections. Nanotechnology offers promising approach in the treatment of VL as it reduces toxicity, improves the therapeutic index of drugs, and can selectively deliver the antileishmanial cargos to the intracellular pathogens. In addition, nanoparticles can interact with the host immune system, modulating the immune response in a way that may favor the elimination of the Leishmania parasites. In this review, we give an overview of the strategies and delivery systems employed for the antileishmanial drugs towards the riddance of deadly VL.

  4. Congenitally transmitted visceral leishmaniasis: report of two brazilian human cases

    Directory of Open Access Journals (Sweden)

    Myrlena Regina Machado Mescouto-Borges

    2013-04-01

    Full Text Available Visceral leishmaniasis is a relevant public health problem worldwide. Most of the reported cases in Latin America are from Brazil. Herein we report two human cases of congenitally transmitted visceral leishmaniasis in two patients who developed symptoms during pregnancy. The diagnosis was made by visual examination of Leishmania parasites in bone marrow aspirates of the mothers and by detecting parasite kDNA in bone marrow samples of the newborn children using polymerase chain reaction.

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

    Directory of Open Access Journals (Sweden)

    Mohammadali Davarpanah

    2015-01-01

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

  6. visceral leishmaniasis with concomittant post kala-azar dermal ...

    African Journals Online (AJOL)

    hi-tech

    East African Medical Journal Vol. 80 No. 8 August 2003. VISCERAL LEISHMANIASIS WITH CONCOMITTANT POST KALA-AZAR DERMAL LEISHMANIASIS RESPONDS TO ORAL SITAMAQUINE: CASE. REPORT. J. Mbui, MBChB, MMed, MSc,Senior Research Officer, R. Rashid, MBChB, MMed, Principal Research Officer, ...

  7. [Visceral leishmaniasis, pemphigus and immunosuppressive treatment: case report from Morocco].

    Science.gov (United States)

    Maleb, A; Messaoudi, N; Chbouki, O; Daoudi, N; Oumghar, K; Lahmadi, K; Elmoussaoui, D; Ezzahraoui, K; Ngoh, Akwa E; Benomar, F; Abi, R; Jeaidi, A; Nazih, M; Belmekki, A; Chakour, M

    2011-02-01

    Atypical forms of visceral leishmaniasis associated with immunosuppressive treatment are difficult to diagnose and cause high mortality. The purpose of this report is to describe a case involving a 42-year-old patient living in a leishmaniasis-endemic area, who was undergoing immunosuppressive treatment using corticosteroids and methotrexate for pemphigus. Despite clinical and laboratory findings consistent with visceral leishmaniasis, detection of Leishmania bodies was a coincidental finding of cytological examination of bone marrow during workup for pancytopenia and associated clinical signs. This case argues in favor of systematic screening for this opportunistic parasitic disease before undertaking immunosuppressive treatment in patients presenting risk factors and consistent clinical/laboratory findings.

  8. KSAC, the first defined polyprotein vaccine candidate for visceral leishmaniasis.

    Science.gov (United States)

    Goto, Yasuyuki; Bhatia, Ajay; Raman, Vanitha S; Liang, Hong; Mohamath, Raodoh; Picone, Alessandro F; Vidal, Silvia E Z; Vedvick, Thomas S; Howard, Randall F; Reed, Steven G

    2011-07-01

    A subunit vaccine using a defined antigen(s) may be one effective solution for controlling leishmaniasis. Because of genetic diversity in target populations, including both dogs and humans, a multiple-antigen vaccine will likely be essential. However, the cost of a vaccine to be used in developing countries must be considered. We describe herein a multiantigen vaccine candidate comprised of antigens known to be protective in animal models, including dogs, and to be recognized by humans immune to visceral leishmaniasis. The polyprotein (KSAC) formulated with monophosphoryl lipid A, a widely used adjuvant in human vaccines, was found to be immunogenic and capable of inducing protection against Leishmania infantum, responsible for human and canine visceral leishmaniasis, and against L. major, responsible for cutaneous leishmaniasis. The results demonstrate the feasibility of producing a practical, cost-effective leishmaniasis vaccine capable of protecting both humans and dogs against multiple Leishmania species.

  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 adults with nephropathy

    Directory of Open Access Journals (Sweden)

    H Kaaroud El Jeri

    2017-01-01

    Full Text Available The aim of this study is to evaluate the features of visceral leishmaniasis (VL in adults with nephropathy, who were not infected with the human immunodeficiency virus. This is a retrospective study of 14 adults hospitalized between 2000 and 2014, with VL and renal involvement. Clinical, biological, and therapeutic data were collected from the patients′ medical files. Eleven women and three men, most of whom were from the North of the country, with a mean age of 40.5 years were studied. Lupus was present in five cases, the Sicca syndrome in three cases, diabetes in one case, renal failure on dialysis in two cases, and there were three renal transplant recipients. Major clinical symptoms were fever and weakness in all cases. Enlargement of the spleen was present in eight cases and hepatomegaly in six cases. Biologic inflammatory syndrome and anemia were present in all cases, and pancytopenia was present in seven cases. Renal insufficiency was noted in all cases. Diagnosis of VL was confirmed by bone marrow examination or serology. Treatment consisted of antimoniate in 10 cases and amphotericin B in four cases. Seven deaths were recorded. Clinical symptoms of VL are atypical in patients with nephropathy and therefore, the diagnosis should be suspected in such patients because VL is still endemic in our country.

  11. Post-kala-azar dermal leishmaniasis in visceral leishmaniasis-endemic communities in Bihar, India.

    Science.gov (United States)

    Singh, Rudra Pratap; Picado, Albert; Alam, Shahnawaz; Hasker, Epco; Singh, Shri Prakash; Ostyn, Bart; Chappuis, François; Sundar, Shyam; Boelaert, Marleen

    2012-11-01

    We assessed the prevalence of post-kala-azar dermal leishmaniasis (PKDL), a late cutaneous manifestation of visceral leishmaniasis (VL), in 16 VL-endemic communities in Bihar, India. The prevalence of confirmed PKDL cases was 4.4 per 10 000 individuals and 7.8 if probable cases were also considered. The clinical history and treatment of the post-kala-azar dermal leishmaniasis cases are discussed. © 2012 Blackwell Publishing Ltd.

  12. 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.

  13. 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.

  14. Visceral leishmaniasis masquerading as tuberculosis in a patient with AIDS

    Science.gov (United States)

    Yaduvanshi, A.; Jain, M.; Jain, S; Jain, S.; Arora, S.

    1999-01-01

    We report a case of visceral leishmaniasis presenting as significant lymphadenopathy in a patient with acquired immune deficiency syndrome. The lymphadenopathy was initially suspected to be tubercular in nature on pathological examination. This report highlights the increasing incidence of acquired immune deficiency syndrome and Leishmania co-infection in India, and the importance of demonstrating tubercle bacilli on culture before suggesting a diagnosis of tuberculosis.


Keywords: leishmaniasis; AIDS; tuberculosis PMID:10567601

  15. Cost of visceral leishmaniasis care in Brazil.

    Science.gov (United States)

    de Carvalho, Isis Polianna Silva Ferreira; Peixoto, Henry Maia; Romero, Gustavo Adolfo Sierra; de Oliveira, Maria Regina Fernandes

    2017-12-01

    To estimate the Brazilian direct and indirect costs of human visceral leishmaniasis (VL) in 2014. Cost-of-illness study on the Brazilian public health system and societal perspective. VL cases registered in the Notifiable Diseases Information System in the year of 2014 were considered. Direct medical costs regarding diagnostic, treatment and care provided to patients with VL were estimated through the top-down approach. The indirect costs related to productivity loss due to premature mortality and morbidity were estimated by means of the human-capital method. In 2014, 9895 suspected cases of VL were reported in the Notifiable Diseases Information System, and 3453 were later confirmed. There were 234 patients with Leishmania-HIV coinfection underwent a secondary prophylaxis. The total cost of VL in Brazil was US$ 14 190 701.50 (US$ 14 189 150.10 to 14 199 940.53) that varied according to the sensitivity analysis. The total of direct medical costs corresponded to US$ 1 873 681.96 (US$1 872 130.55 to 1 882 920.99), and the majority of costs was associated with hospitalisation (40%), followed by treatment (22%), and secondary prophylaxis (18%). Productivity loss corresponded to US$ 11 421 683.37 for premature mortality and US$ 895 336.18 for work absence due to hospitalisation by the illness. VL represents an expensive health problem for the Brazilian public health system and society, mainly because of its productivity loss due to premature mortality. Interventions to reduce VL lethality could have a great impact on decreasing the cost of illness. © 2017 John Wiley & Sons Ltd.

  16. 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. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  17. [Uncommon cutaneous presentation of visceral Leishmaniasis associated with HIV].

    Science.gov (United States)

    Cossart, C; Le Moal, G; Garcia, M; Frouin, E; Hainaut-Wierzbicka, E; Roblot, F

    2016-12-01

    Visceral leishmaniasis is not normally expressed in skin. Herein, we describe the case of an HIV-positive patient who developed two unusual skin manifestations during an episode of visceral leishmaniasis. A 48-year-old female patient consulted initially for infiltrated purpura of all four limbs. Skin biopsy revealed leukocytoclastic vasculitis with Leishman-Donovan bodies. Laboratory tests showed medullary, splenic, gastric and colic involvement, suggesting systemic disease, and enabling visceral leishmaniasis to be diagnosed. Two years later, despite prolonged treatment, the patient presented maculopapular exanthema, and histology revealed persistent Leishman-Donovan bodies. We report herein an association of two rare skin manifestations in an HIV-positive patient with visceral leishmaniasis: infiltrated purpura and maculopapular exanthema. However, the underlying mechanisms remain hypothetical. The initial leukocytoclastic exanthema could be secondary to either polyclonal hypergammaglobulinaemia or to IgA deposits, or possibly to mechanical impairment of blood vessels by the actual parasite. The maculopapular exanthema occurring later raised the possibility of post-Kala-Azar leishmaniasis due to blood-borne dissemination in an anergic subject or perhaps even immune reconstitution inflammatory syndrome. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Cutaneous and visceral leishmaniasis during anti-TNFα therapy.

    Science.gov (United States)

    Guarneri, Claudio; Bevelacqua, Valentina; Patterson, James W; Tchernev, Georgi

    2017-03-01

    The long-term use of novel antipsoriatic systemic biotechnological drugs may increase susceptibility to opportunistic infections. Several cases of visceral leishmaniasis have been reported in immunosuppressed individuals, including those who have been treated with tumour necrosis factor alpha (TNFα) blocking agents. Simultaneous occurrence of cutaneous and visceral involvement has been more rarely recorded in the medical literature. Herein, we describe a case of mucosal leishmaniasis occurring in a farmer living in an endemic region, who was treated with golimumab because of psoriatic arthritis. This highlights the importance of recognizing cutaneous lesions as a first indicator of possible underlying kala-azar disease.

  19. 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

  20. 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

  1. visceral leishmaniasis with concomittant post kala-azar dermal ...

    African Journals Online (AJOL)

    hi-tech

    2003-08-08

    Aug 8, 2003 ... province, Kenya. INTRODUCTION. Visceral Leishmaniasis or kala-azar is caused by species of Leishmania donovani complex. These are Leishmania donovani donovani in East Africa and Asia, Leishmania donovani infantum in the Mediterranean Basin and. Leishmania donovani chagasi in Latin America ...

  2. Development and application of 'simple' diagnostic tools for visceral leishmaniasis

    NARCIS (Netherlands)

    Schallig, H. D.; Schoone, G. J.; Kroon, C. C.; Hailu, A.; Chappuis, F.; Veeken, H.

    2001-01-01

    The diagnosis of visceral leishmaniasis is difficult. Due to the limitations of direct methods to detect parasites, indirect immunological methods are widely employed. The simple affordable and sensitive/specific direct agglutination test (DAT) is perhaps the most important diagnostic tool under

  3. Visceral leishmaniasis in Northern Ethiopia | Haile | East African ...

    African Journals Online (AJOL)

    Background: Visceral leishmaniasis (VL) has been well documented by the Medecins sans Frontieres (MSF) VL treatment programmeme in the Tigray region of Ethiopia, but reports are limited from other facilities in this region where this disease continues to cause substantial morbidity and mortality. Objective: To describe ...

  4. Pediatric visceral leishmaniasis in Western Sicily, Italy: a retrospective analysis of 111 cases.

    Science.gov (United States)

    Cascio, A; Colomba, C; Antinori, S; Orobello, M; Paterson, D; Titone, L

    2002-04-01

    The clinical and epidemiological characteristics of 111 consecutive cases of visceral leishmaniasis identified from 1980 to 2000 in a Sicilian pediatric hospital were analyzed retrospectively. The mean age of the patients was 1.7 years. All children were HIV negative, but 15% were severely malnourished. Fever and splenomegaly were present in all cases and hepatomegaly in 101 (90.1%) cases. Thrombocytopenia and anemia were both observed in 78 (70.2%) cases and leukopenia in 47 (42.3%) cases. A bone marrow aspirate was obtained in all cases; Leishmania amastigotes were detected in 89 (80.2%) cases. Initial treatment consisted of meglumine antimoniate in 99 (89.2%) patients and amphotericin B in 12 (10.8%) patients. Only two children treated with meglumine antimoniate relapsed. The findings highlight the differences between the cases of visceral leishmaniasis observed in the Mediterranean basin and those observed in other regions. The use of the term "Mediterranean visceral leishmaniasis", rather than the term "kala-azar", is proposed for cases observed in the Mediterranean area.

  5. 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)

  6. Visceral Leishmaniasis in Latin America and therapy perspectives

    Directory of Open Access Journals (Sweden)

    Catalina Tovar A

    2017-05-01

    Full Text Available In Latin America, visceral leishmaniasis is caused by Leishmania infantum. In this geographical area, main vectors associated with transmission are Lutzomyia longipalpis and Lutzomyia evansi, with dogs being incriminated as the main reservoir involved in transmission of the disease. This pathology primarily affects children between 0 - 5 years, a highly susceptible population where socio-economic, environmental and nutritional factors affects the pathological outcome and increase the likelihood of vector-human contact. According to the World Health Organization (WHO recommended treatment for Visceral Leishmaniasis is liposomal amphotericin B, a drug with a limited and variable availability between countries depending on market prices, which leaves pentavalent antimonial as the most widely used treatment despite the associated toxic effects. In the Americas, evidence on the efficacy of single-dose (monotherapy and combination therapies as options for treating these parasites is required.

  7. Canine Visceral Leishmaniasis, United States and Canada, 2000–2003

    OpenAIRE

    Duprey, Zandra H.; Steurer, Francis J.; Rooney, Jane A.; Kirchhoff, Louis V.; Jackson, Joan E.; Rowton, Edgar D.; Peter M. Schantz

    2006-01-01

    Visceral leishmaniasis, caused by protozoa of the genus Leishmania donovani complex, is a vectorborne zoonotic infection that infects humans, dogs, and other mammals. In 2000, this infection was implicated as causing high rates of illness and death among foxhounds in a kennel in New York. A serosurvey of >12,000 foxhounds and other canids and 185 persons in 35 states and 4 Canadian provinces was performed to determine geographic extent, prevalence, host range, and modes of transmission within...

  8. Sodium stibogluconate and paromomycin for treating visceral leishmaniasis under routine conditions in eastern Sudan.

    Science.gov (United States)

    Atia, Atia M; Mumina, Ann; Tayler-Smith, Katherine; Boulle, Philippa; Alcoba, Gabriel; Elhag, Mousab Siddig; Alnour, Mubarak; Shah, Safieh; Chappuis, François; van Griensven, Johan; Zachariah, Rony

    2015-12-01

    Among patients with primary and relapse visceral leishmaniasis (VL) in eastern Sudan, we determined the proportion eligible for treatment with sodium stibogluconate and paromomycin (SSG/PM) and, of these, their demographic and clinical characteristics; initial treatment outcomes including adverse side effects requiring treatment discontinuation; treatment outcomes by 6 months; and risk factors associated with initial (slow responders) and late treatment failure (relapses and post-kala-azar dermal leishmaniasis, PKDL). A retrospective cohort study in Tabarak Allah Hospital, Gedaref Province, eastern Sudan, from July 2011 to January 2014. Of 1252 individuals diagnosed with VL (1151 primary and 101 relapses), 65% were eligible for SSG/PM including 83% children, almost half of them malnourished and anaemic. About 4% of individuals discontinued treatment due to side effects; 0.7% died during treatment. Initial cure was achieved in 93% of 774 primary cases and 77% of 35 relapse cases (P Sudan. © 2015 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  9. Prevalence of Human Immunodeficiency Virus and associated factors among Visceral Leishmaniasis infected patients in Northwest Ethiopia: a facility based cross-sectional study.

    Science.gov (United States)

    Alemayehu, Mekuriaw; Wubshet, Mamo; Mesfin, Nebiyu; Gebayehu, Abebaw

    2017-02-17

    Visceral Leishmaniasis coinfection with HIV/AIDS has emerged as a series of disease pattern. It most often results in unfavorable responses to treatment, frequent relapses, and deaths. Scarce data is available regarding the prevalence of HIV and associated factors among Visceral Leishmaniasis coinfected patients. This study sought to determine the prevalence of HIV and associated factors among Visceral Leishmaniasis infected patients. Facility based cross-sectional study was conducted from October, 2015 to August, 2016 in Northwest Ethiopia. Cluster sampling technique was used to select 462 Visceral Leishmaniasis infected patients. Serologic and parasitological test results have been used to diagnose Visceral Leishmaniasis. The HIV diagnosis was based on the national algorithm with two serial positive rapid test results. In case of discrepancy between the two tests, Uni-Gold TM was used as a tie breaker. Structured questionnaire was used to collect independent variables. Data was entered by using Excel and analyzed by using SPSS version 20. Descriptive statistics and logistic regression model was used to analyze the data. A total of 462 study participants were included in the study with a response rate of 92.4%. HIV and Visceral Leishmaniasis coinfection was found to be 17.75% with 95% CI; 14.30-21.40. Age ≥ 30 years (AOR = 22.58, 95% CI 11.34, 45.01), urban residents (AOR = 2.02, 95% CI 1.16, 4.17) and daily laborer workers (AOR = 4.99, 95% CI 2.33, 10.68) were significantly associated with HIV and Visceral Leishmaniasis coinfection. HIV and Visceral Leishmaniasis coinfection in the Northwest Ethiopia was found to be low. Age, residence and employment were independently associated with HIV-VL coinfection in the Northwest Ethiopia. It is better to design interventions to prevent and control HIV-VL coinfection for productive age groups (age ≥ 30) and daily laborers.

  10. Blood pressure and renal injury in dogs with visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Marlos G. Sousa

    Full Text Available Abstract: Systemic hypertension is known to be a common consequence of chronic renal disease, which is frequently diagnosed in dogs with visceral leishmaniasis. Although many veterinary investigations have looked at the renal injury caused by Leishmania spp., the role played by this complication in the development of arterial hypertension documented in some animals with visceral leishmaniasis is not completely understood. In this study, 18 adult dogs with naturally-occurring visceral leishmaniasis and varying clinical signs underwent an indirect blood pressure measurement. Also, sera and spot urine were used for laboratory tests. The median systolic blood pressure was 135.2mmHg (95% confidence interval: 128.5-147.7, median mean arterial pressure was 105.8mmHg (98.3-110.4, and median diastolic arterial pressure was 88.5mmHg (77.8-92.5. No differences existed between asymptomatic and symptomatic animals regarding arterial pressure, and no correlations were documented between blood pressure and serum creatinine, blood urea, urine protein-to-creatinine ratio, urine specific gravity, and the fractional excretion of sodium and potassium. Although an association between hypertension and the identification of inflammation on histopathology could not be demonstrated in hypertensive animals, the assessment of kidney samples from 12 dogs indicated mild inflammation with a lymphoplasmacytic infiltrate (6/12, moderate inflammation with multifocal lymphoplasmacytic and histiocytic infiltrates (3/12, and multifocal degeneration and protein casts (2/12. Anti-Leishmania spp. immunohistochemistry assays stained the renal epithelium in 2/12 of the animals. Even though mild systemic hypertension was documented in a small subset of animals, no relationship between the severity of clinical signs and hypertension could be anticipated.

  11. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    Directory of Open Access Journals (Sweden)

    Leslie Shanks

    Full Text Available Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals.Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367 in the VL group compared to 7.9% (200/2526 in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively.The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

  12. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    Science.gov (United States)

    Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

    2015-01-01

    Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

  13. 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. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  14. Host resistance to visceral leishmaniasis: prevalence and prevention.

    Science.gov (United States)

    Maran, Naiara; Gomes, Pollyanna Stephanie; Freire-de-Lima, Leonardo; Freitas, Elisangela Oliveira; Freire-de-Lima, Célio Geraldo; Morrot, Alexandre

    2016-01-01

    Visceral leishmaniasis (VL) is a chronic parasitic disease caused by the vector-borne Leishmania donovani and Leishmania (L.) infantum chagasi parasites. The disease affects about 12 million humans in more than 90 countries worldwide. If not treated, the visceral form of Leishmania infection is potentially fatal, yielding about 50000 deaths per year. In the vertebrate host, the Leishmania species causing VL spread systematically to propagate in macrophage reservoirs distributed in the tissues of internal organs, primarily the liver, spleen, bone marrow and the lymph nodes. The infection is associated with evolved mechanisms from the parasite to subvert the host immune system in order to establish a persistent infection. Currently, efforts are being deployed to develop new anti-leishmanial therapies in VL combining immunomodulatory treatment regimens that burst the host immune responses together with leishmanicidal drugs that target the parasite growth. Discoveries in this field are discussed in this article.

  15. The economic impact of visceral leishmaniasis on households in Bangladesh.

    Science.gov (United States)

    Anoopa Sharma, D; Bern, Caryn; Varghese, Beena; Chowdhury, Rajib; Haque, Rashidul; Ali, Mustakim; Amann, Josef; Ahluwalia, Indu B; Wagatsuma, Yukiko; Breiman, Robert F; Maguire, James H; McFarland, Deborah A

    2006-05-01

    To explore current patterns of diagnosis and treatment, quantify household economic impact and identify household strategies to cover the costs of visceral leishmaniasis (VL) care in rural Bangladesh. Structured interviews with 113 VL patients from 87 households documenting all provider visits and expenditures for health care for VL, and the ways in which the expenditures were covered. Patients paid a median of 7 visits to six different providers before beginning VL treatment. All visited the subdistrict government hospital at least once. While health care, including antileishmanial drug therapy, is officially available free of charge at government facilities, 79% of patients reported making informal payments for provider access, diagnostics and drug administration; only 14% of patients received their full drug course from this source. For the 58% of patients who purchased the full treatment course, drug cost constituted 34% of direct expenditure. Median direct expenditure for one VL patient was US$87 and median income lost was $40; median total expenditure was 1.2 times annual per capita income of our study population. Households employed multiple coping strategies to cover expenditures, most commonly sale or rental of assets (62%) and taking out loans (64%). Visceral leishmaniasis treatment causes a major economic burden in affected families. Control strategies for VL should facilitate timely, affordable diagnosis and treatment of patients to decrease the infection reservoir and to alleviate the economic burden of VL on households.

  16. 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.

  17. Live Vaccination Tactics: Possible Approaches for Controlling Visceral Leishmaniasis

    Science.gov (United States)

    Saljoughian, Noushin; Taheri, Tahareh; Rafati, Sima

    2014-01-01

    Vaccination with durable immunity is the main goal and fundamental to control leishmaniasis. To stimulate the immune response, small numbers of parasites are necessary to be presented in the mammalian host. Similar to natural course of infection, strategy using live vaccine is more attractive when compared to other approaches. Live vaccines present the whole spectrum of antigens to the host immune system in the absence of any adjuvant. Leishmanization was the first effort for live vaccination and currently used in a few countries against cutaneous leishmaniasis, in spite of their obstacle and safety. Then, live attenuated vaccines developed with similar promotion of creating long-term immunity in the host with lower side effect. Different examples of attenuated strains are generated through long-term in vitro culturing, culturing under drug pressure, temperature sensitivity, and chemical mutagenesis, but none is safe enough and their revision to virulent form is possible. Attenuation through genetic manipulation and disruption of virulence factors or essential enzymes for intracellular survival are among other approaches that are intensively under study. Other designs to develop live vaccines for visceral form of leishmaniasis are utilization of live avirulent microorganisms such as Lactococcus lactis, Salmonella enterica, and Leishmania tarentolae called as vectored vaccine. Apparently, these vaccines are intrinsically safer and can harbor the candidate antigens in their genome through different genetic manipulation and create more potential to control Leishmania parasite as an intracellular pathogen. PMID:24744757

  18. Therapeutic effect of ursolic acid in experimental visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    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.

  19. Lutzomyia longipalpis (Diptera, Psychodidae, Phlebotominae) and urbanization of visceral leishmaniasis in Brazil.

    Science.gov (United States)

    Rangel, Elizabeth F; Vilela, Maurício L

    2008-12-01

    The article discusses habits related to the vectorial competence of Lutzomyia longipalpis, along with evidence confirming the importance of this sand fly species in the epidemiological chain of visceral leishmaniasis in Brazil. A new epidemiological profile for visceral leishmaniasis is also postulated, associated with domestic environments and the role of Lu. longipalpis in this process, its sylvatic origin, and its capacity to adapt to a wide range of habitats. Another sand fly species, Lu. cruzi, is mentioned as a vector of visceral leishmaniasis in some municipalities in Central Brazil, based on studies in endemic areas of the country.

  20. AA-amyloidosis caused by visceral leishmaniasis in a human immunodeficiency virus-infected patient.

    Science.gov (United States)

    de Vallière, Serge; Mary, Charles; Joneberg, Jeanna E; Rotman, Samuel; Bullani, Roberto; Greub, Gilbert; Gillmore, Julian D; Buffet, Pierre A; Tarr, Philip E

    2009-08-01

    AA-amyloidosis in the setting of chronic visceral leishmaniasis (VL) has been reported in animal models but documentation in humans is unavailable. Here, we report on a Portuguese man who in 1996 was diagnosed with both human immunodeficiency virus (HIV)-infection and VL. Antiretroviral treatment led to sustained suppression of HIV viremia but CD4+ lymphocytes rose from 8 to only 160 cells/mL. Several courses of antimony treatment did not prevent VL relapses. Renal failure developed in 2006 and renal biopsy revealed AA-amyloidosis. The patient had cryoglobulinemia and serum immune complexes containing antibodies directed against seven leishmanial antigens. Antimony plus amphotericin B, followed by oral miltefosine resulted in a sustained VL treatment response with elimination of circulating Leishmania infantum DNA and CD4+ recovery. The concomitant reduction of serum AA levels and disappearance of circulating leishmanial immune complexes suggests that prolonged VL may lead to AA-amyloidosis in immunocompromised humans.

  1. The direct agglutination test as an alternative method for the diagnosis of canine and human visceral leishmaniasis

    NARCIS (Netherlands)

    Terán-Angel, Guillermo; Schallig, Henk; Zerpa, Olga; Rodríguez, Vestalia; Ulrich, Marian; Cabrera, Maira

    2007-01-01

    Visceral leishmaniasis is the most severe clinical form of leishmaniasis and is often fatal without proper treatment. Therefore, early and accurate diagnosis is important, but often difficult in endemic areas. The aim was to evaluate a direct agglutination test as a potential visceral leishmaniasis

  2. 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.

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

    Science.gov (United States)

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

    2016-01-01

    Leishmania/Human Immunodeficiency Virus (HIV) coinfection has emerged as an extremely serious and increasingly frequent health problem in the last decades. Considering the insidious and not typical clinical picture in presence of immunosuppressive conditions, the increasing number of people travelling in endemic zones, the ability to survive, within both human and vector bodies, of the parasite, clinicians and dermatologists as the first line should be aware of these kind of "pathologic alliances," to avoid delayed diagnosis and treatment. In this setting, the occurrence of cutaneous lesions can, paradoxically, aid the physician in recognition and approaching the correct staging and management of the two (or three) diseases. Treatment of these unwelcome synergies is a challenge: apart from the recommended anti-retroviral protocols, different anti-leishmanial drugs have been widely used, according with the standard guidelines for visceral leishmaniasis (VL), with no successful treatment regimen still been established. © 2015 Wiley Periodicals, Inc.

  4. Clinical severity of visceral leishmaniasis is associated with changes in immunoglobulin g fc N-glycosylation.

    NARCIS (Netherlands)

    Gardinassi, L.G.; Dotz, V.; Hipgrave Ederveen, A.; de Almeida, R.P.; Nery Costa, C.H.; Costa, D.L.; de Jesus, A.R.; Mayboroda, O.A.; Garcia, G.R.; Wuhrer, M.; de Miranda Santos, I.K.

    2014-01-01

    Visceral leishmaniasis (VL) has a high fatality rate if not treated; nevertheless, the majority of human infections with the causative agent, Leishmania infantum chagasi, are asymptomatic. Although VL patients often present with increased levels of serum immunoglobulins, the contribution of

  5. Failure of miltefosine in visceral leishmaniasis is associated with low drug exposure

    NARCIS (Netherlands)

    Dorlo, Thomas P C; Rijal, Suman; Ostyn, Bart; de Vries, Peter J; Singh, Rupa; Bhattarai, Narayan; Uranw, Surendra; Dujardin, Jean-Claude; Boelaert, Marleen; Beijnen, Jos H; Huitema, Alwin D R

    2014-01-01

    BACKGROUND: Recent reports indicated high miltefosine treatment failure rates for visceral leishmaniasis (VL) on the Indian subcontinent. To further explore the pharmacological factors associated with these treatment failures, a population pharmacokinetic-pharmacodynamic study was performed to

  6. SLC11A1 polymorphisms and susceptibility to visceral leishmaniasis in Moroccan patients.

    Science.gov (United States)

    Ejghal, Rajaâ; Hida, Moustapha; Idrissi, Mona Lakhdar; Hessni, Aboubaker El; Lemrani, Meryem

    2014-12-01

    Human visceral leishmaniasis is endemic in the Mediterranean basin. Since most infections are sub-clinical or asymptomatic, host genetics can provide concrete evidence in determining disease outcome. SLC11A1/NRAMP1 is a candidate gene that may be related to host susceptibility versus resistance to intracellular pathogens. This study aimed to determine possible association of SLC11A1 polymorphisms with visceral leishmaniasis among Moroccan children. A total of 106 children who developed visceral leishmaniasis due to Leishmania infantum were enrolled in this study. The control group was composed of 137 unrelated children, 97 asymptomatic subjects (DTH+) and 42 healthy individuals (DTH) who had no evidence of present or past infection. Four polymorphisms were studied by PCR-RFLP and sequencing: (GT)n microsatellite in the 5' exon 1; silent substitutions 469+14G/C in intron 4; amino acid substitution D543N in exon 15 and 823C/T polymorphism in exon 8. Thereafter, the frequencies of genotypes, alleles and haplotypes were estimated. Two polymorphisms were each significantly associated in the genotypes with visceral leishmaniasis: 823C/T in exon 8 and D543N in exon 15 when comparing visceral leishmaniasis and DTH+ groups. The results of haplotype frequencies suggested an evidence of association with resistance to visceral leishmaniasis for the "286GTG" and "288GCA" haplotypes, whereas, the "286GCG" haplotype appears to increase the risk to visceral leishmaniasis susceptibility.Our data provide insights into the possible role of SLC11A1 variation in visceral leishmaniasis susceptibility. These results must be regarded as preliminary but suggestive that further study with larger populations is worthwhile. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Visceral leishmaniasis with cutaneous symptoms in a patient treated with infliximab followed by fatal consequences.

    Science.gov (United States)

    Juzlova, Katerina; Votrubova, Jana; Kacerovska, Denisa; Lukas, Milan; Bortlik, Martin; Rohacova, Hana; Nohynkova, Eva; Vojackova, Nadezda; Fialova, Jorga; Hercogova, Jana

    2014-01-01

    Leishmaniasis is an infectious disease caused by parasitic flagellates of the genus Leishmania. The authors present a case of 44-year-old man with Crohn's disease treated successfully with infliximab. This case report shows rare visceral leishmaniasis with cutaneous symptoms in an immunocompromised patient. Skin manifestations may occur before or after the visceral infection and they are often diverse. © 2013 Wiley Periodicals, Inc.

  8. Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis

    OpenAIRE

    Sharma, Meenakshi; Sehgal, Rakesh; Kaur, Sukhbir

    2012-01-01

    BACKGROUND: Most available drugs against visceral leishmaniasis are toxic, and growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine against visceral leishmaniasis deepens the crisis. Antineoplastic drugs like miltefosine have in the past been effective against the parasitic infections. An antineoplastic drug, cisplatin (cis-diamminedichloroplatinum II; CDDP), is recognized as a DNA-damaging drug which also induces alte...

  9. Vulnerability to the transmission of human visceral leishmaniasis in a Brazilian urban area

    Directory of Open Access Journals (Sweden)

    Celina Roma Sánchez de Toledo

    Full Text Available ABSTRACT OBJECTIVE To analyze the determinants for the occurrence of human visceral leishmaniasis linked to the conditions of vulnerability. METHODS This is an ecological study, whose spatial analysis unit was the Territorial Analysis Unit in Araguaína, State of Tocantins, Brazil, from 2007 to 2012. We have carried out an analysis of the sociodemographic and urban infrastructure situation of the municipality. Normalized primary indicators were calculated and used to construct the indicators of vulnerability of the social structure, household structure, and urban infrastructure. From them, we have composed a vulnerability index. Kernel density estimation was used to evaluate the density of cases of human visceral leishmaniasis, based on the coordinates of the cases. Bivariate global Moran’s I was used to verify the existence of spatial autocorrelation between the incidence of human visceral leishmaniasis and the indicators and index of vulnerability. Bivariate local Moran’s I was used to identify spatial clusters. RESULTS We have observed a pattern of centrifugal spread of human visceral leishmaniasis in the municipality, where outbreaks of the disease have progressively reached central and peri-urban areas. There has been no correlation between higher incidences of human visceral leishmaniasis and worse living conditions. Statistically significant clusters have been observed between the incidences of human visceral leishmaniasis in both periods analyzed (2007 to 2009 and 2010 to 2012 and the indicators and index of vulnerability. CONCLUSIONS The environment in circumscribed areas helps as protection factor or increases the local vulnerability to the occurrence of human visceral leishmaniasis. The use of methodology that analyzes the conditions of life of the population and the spatial distribution of human visceral leishmaniasis is essential to identify the most vulnerable areas to the spread/maintenance of the disease.

  10. [Epidemiology of leishmaniasis in Algeria. 6. Survey of clinical cases of infantile visceral leishmaniasis from 1965 to 1974].

    Science.gov (United States)

    Addadi, K; Dedet, J P

    1976-01-01

    The authors present the results of an inquiry conducted in the principal hospitals of Algeria. The number of cases of visceral leishmaniasis recorded over the last ten years (1965 to 1974) totaled 497. The disease occurs essentially in children under 5 years of age (94%); it is mainly detected in central and eastern parts of the Tell region: principally in the Grande Kabylie, Algerois and Constantinois areas (humid and sub-humid bioclimatic stages). The results of the malaria eradication campaign in relation to the incidence of visceral Leishmaniasis is discussed.

  11. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. 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.

  13. 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...

  14. Clinical characteristics and spatial distribution of Visceral leishmaniasis in children in São Paulo state: an emerging focus of Visceral leishmaniasis in Brazil

    Science.gov (United States)

    Naufal Spir, Patricia Rodrigues; Prestes-Carneiro, Luiz Euribel; Fonseca, Elivelton Silva; Dayse, Aline; Giuffrida, Rogério

    2017-01-01

    Background: Visceral leishmaniasis (VL) is an emerging zoonosis, and Brazil harbors about 90% of those infected in Latin America. Since 1998, the disease has been spreading quickly in São Paulo state, and the western region is considered an emerging focus of VL in Brazil. Our aim was to evaluate the clinical characteristics and spatial distribution of VL in children referred to a public tertiary hospital located in the western region of São Paulo state, Brazil. Methods: Medical records of children up to 18 years of age who were diagnosed with VL between January 2006 and December 2010 were reviewed. Geospatial analysis was performed using the ArcGIS 10.2 platform. Results: Sixty-three patients were enrolled in the study; the median age was 3.3 ± 3.3 years. The median time interval between the onset of clinical symptoms and diagnosis was 16.1 ± 11.1 days, and the median time in the pediatric ward was 18.0 ± 9.4 days. Liposomal amphotericin B was the first-line treatment in 90.5% of the patients and 9.6% relapsed. One patient died (1.6%), and 19% were submitted to the pediatric intensive care unit. Conclusion: The short interval between the onset of symptoms, diagnosis, and treatment and the reduced number of days of hospitalization certainly influenced the small number of deaths, relapses, and severity among the children infected with VL. However, the disease is spreading fast in the western region of São Paulo state. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices. PMID:28221822

  15. Recent understanding in the treatment of visceral leishmaniasis.

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    Rosenthal E

    2003-01-01

    Full Text Available Visceral leishmaniasis (VL is a severe disease associated with infection of the reticuloendothelial system by Leishmania species. The infection is acquired through sandfly bites. Recent large scale epidemics of VL in east Africa and India and the emergence of a HIV epidemic make VL a priority for the World Health Organization. Pentavalent antimonials have been cornerstone of treatment for the last six decades. The appearance of antimonial-resistance and the development of lipid formulations of amphotericin B have changed the pattern of VL treatment. Within the past five years, miltefosine has been demonstrated as the first effective and safe oral treatment against VL. The price of miltefosine is yet to be determined. However, miltefosine will certainly be cheaper than lipid formulations of amphotericin B, which are beyond the financial capacity of the poor countries. Because it can be administered orally, miltefosine is suited for the treatment of large number of patients who get affected during epidemics, particularly in regions where the parasites are resistant to the currently used agents. Here, we recommend different treatment schedules according to the resistance pattern and the region-specific socio-economical and cultural factors.

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

    Science.gov (United States)

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

    2012-03-01

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

  17. Clinical and hematological manifestations of visceral leishmaniasis in Yemeni children

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    Gamal Abdul Hamid

    2009-03-01

    Full Text Available Objective: In southeast Yemen, visceral leishmaniasis (VL is endemic in Lahj and Abyan and also in Hagga and Sadah, the areas lacking adequate diagnostic facilities. This study describes the clinical and hematological features in 64 cases of childhood VL.Material and Methods: All children below 12 years of age who were managed as inpatient cases from 1 January to 31 December 2005 were included in this study. The diagnosis of VL was established by demonstration of leishmania parasites in bone marrow aspiration. Demographic information, physical signs at presentation and results of complete blood count were recorded and bone marrow aspirations were done for LD bodies. Results: Mean age of the patients was 30 months, and there were 33 females and 31 males. Fever was seen in 100% of children with duration before diagnosis of 56 days. Splenomegaly was present in all cases and hepatomegaly in 84.4%, with mean enlargement of spleen and liver of 9.3 and 3.5 cm, respectively. Mean hemoglobin level, white blood cell and platelet counts were 6.6 g/dl, 3.58x109 /L and 71.7x109 /L, respectively. Absolute neutrophil count was <0.78x109 /L and mean reticulocyte count was 1.7%.Conclusion: Fever, hepatosplenomegaly and pancytopenia were the most common clinical and hematological manifestations in Yemeni children with VL.

  18. Immunohistochemical study of hepatic fibropoiesis associated with canine visceral leishmaniasis.

    Science.gov (United States)

    Madeira, Igor M V M; Pereira, Debora M O; Sousa, Aline A; Vilela, Cesar A; Amorim, Izabela F G; Caliari, Marcelo V; Souza, Carolina C; Tafuri, Wagner L

    2016-04-01

    Hepatic fibropoiesis has been confirmed in canine visceral leishmaniasis. In fibrotic disease, hepatic stellate cells (HSC) play an important role in fibropoiesis, undergoing activation by TGF-β to acquire characteristics of myofibroblasts. These cells show extensive capacity for proliferation, motility, contractility, collagen synthesis and extracellular matrix component synthesis. The aim of this work was to identify markers of HSC activation in 10 symptomatic and 10 asymptomatic dogs naturally infected with Leishmania (Leishmania) infantum. Eight uninfected dogs were used as controls. Alpha-actin (α-SMA), vimentin and cytokeratin were investigated by immunohistochemistry as HSC markers. The cytokine TGF-β in tissue was also evaluated by immunohistochemistry. All infected dogs showed higher numbers of reticular fibres than controls. Fibropoiesis found in infected dogs was always associated with the presence of parasites and chronic granulomatous hepatitis. Positive correlation was found among fibropoiesis, parasite tissue load and expression of α-SMA. There was no correlation between fibropoiesis, vimentin and cytokeratin markers. The expression of cytokine TGF-β was higher in infected dogs than in controls, but not significantly different between symptomatic and asymptomatic dogs. These results confirm previous work describing the intense hepatic fibropoiesis in dogs naturally infected with Leishmania infantum, but now associated them with overexpression of TGF-β, where α-SMA may be a superior marker for activated HSC cells in CVL. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  19. Visceral leishmaniasis and peritoneal tuberculosis: a case report

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    Zamani A

    2009-03-01

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

  20. Outbreak of autochthonous canine visceral leishmaniasis in Santa Catarina, Brazil

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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.

  1. Perceptions of the population and health professionals regarding visceral leishmaniasis.

    Science.gov (United States)

    Carmo, Rose Ferraz; da Luz, Zélia Maria Profeta; Bevilacqua, Paula Dias

    2016-02-01

    Based on theoretical qualitative research reference methodology, this study sought to investigate the perception of visceral leishmaniasis (VL) by social actors directly involved in the prevention and control of the disease. Thirty-eight semi-structured interviews were conducted with residents, focus groups were staged with 18 health workers in an endemic VL area and depositions were collected, which after being processed by content analysis revealed shortcomings and challenges. The population associated VL with dogs, acknowledged their co-responsibility in tackling the disease and demanded information. Health workers identified environmental sanitation as an essential factor for VL prevention. Among the shortcomings, the lack of information about the disease and culpability of the individual because of non-adherence to prevention measures were observed, especially environmental management. Probably, approaches emphasizing the role of the environment as a health promotion agent and the timely definition of specific environmental measures against VL, constitute a prospect for overcoming these shortcomings. The consensus is that the main challenge for enhancing the prevention and control might be the participatory and dialogical construction of these approaches between health professionals and the population.

  2. Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis

    Science.gov (United States)

    Soong, Lynn; Henard, Calvin A.; Melby, Peter C.

    2014-01-01

    The outcomes of Leishmania infection are determined by host immune and nutrition status, parasite species, and co-infection with other pathogens. While subclinical infection and self-healing cutaneous leishmaniasis (CL) are common, uncontrolled parasite replication can lead to non-healing local lesions or visceral leishmaniasis (VL). It is known that infection control requires Th1-differentiation cytokines (IL-12, IL-18, and IL-27) and Th1 cell and macrophage activation. However, there is no generalized consensus for the mechanisms of host susceptibility. The recent studies on regulatory T cells and IL-17-producing cells help explain the effector T cell responses that occur independently of the known Th1/Th2 cell signaling pathways. This review focuses on the immunopathogenesis of non-healing American CL and progressive VL. We summarize recent evidence from human and animal studies that reveals the mechanisms of dysregulated, hyper-responses to Leishmania braziliensis, as well as the presence of disease-promoting or the absence of protective responses to Leishmania amazonensis and Leishmania donovani. We highlight immune-mediated parasite growth and immunopathogenesis, with an emphasis on the putative roles of IL-17 and its related cytokines as well as arginase. A better understanding of the quality and regulation of innate immunity and T cell responses triggered by Leishmania will aid in the rational control of pathology and the infection. PMID:23053396

  3. 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.

  4. Electrospray Encapsulation of Toll-Like Receptor Agonist Resiquimod in Polymer Microparticles for the Treatment of Visceral Leishmaniasis

    Science.gov (United States)

    2013-01-15

    SECURITY CLASSIFICATION OF: Leishmaniasis is a disease caused by the intracellular protozoan, Leishmania. A current treatment for cutaneous... leishmaniasis involves the delivery of imidazoquinolines via a topical cream. However, there are no parenteral formulations of imidazoquinolines for the most...deadly version of the disease, visceral leishmaniasis . This work investigates the use of electrospray to encapsulate the imidazoquinoline adjuvant

  5. Risk factors, representations and practices associated with emerging urban human visceral leishmaniasis in Posadas, Argentina.

    Science.gov (United States)

    López, Karen; Tartaglino, Lilian Catalina; Steinhorst, Ingrid Iris; Santini, María Soledad; Salomon, Oscar Daniel

    2016-02-23

    Visceral leishmaniasis is an often overlooked disease with high lethality rates about which there is need of additional local studies to inform the design of effective control strategies. The urbanization of its transmission has already been verified in America, with domestic dogs being the primary reservoirs and vectors of the disease. Socio-economic conditions, demographics and practices of domestic groups typically present in urban settings may play a specific role in the transmission of the infection, which is still poorly understood.  To analyze the sociodemographic characteristics, risk factors and overall practices concerning prevention and coping strategies of visceral leishmaniasis, in both human beings and canines.  This study utilized a cross-sectional case-control design. Cases were defined as a domestic group where the Public Health Ministry had at least one record of a member with human visceral leishmaniasis. Control cases were defined as a domestic group without a clinical record of the disease. The populations were characterized demographically and socially using primary information sources. Measures of household quality and a ranking of knowledge and attitudes towards visceral leishmaniasis were constructed, and practices associated with the presence, and the risk for canine visceral leishmaniasis were described.  Low household quality (p≤0.001), a member of the domestic group out of the household after 6:00 pm (OR=4.4; 95% CI: 1.69-12.18), the uncontrolled racial breeding of dogs (OR=15.7; 95% CI: 3.91-63.2), and the presence of infected dogs infected in the household (OR=120.3; 95% CI: 18.51-728.3) were variables positively associated with the risk of infection.  We observed certain social risk factors, primarily low household quality and overcrowding, associated with structural poverty that could increase human-vector contact probability. The most important risk factor for human visceral leishmaniasis was the possession of infected dogs

  6. Risk factors for death in children with visceral leishmaniasis.

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    Márcia Jaqueline Alves de Queiroz Sampaio

    Full Text Available BACKGROUND: Despite the major public health importance of visceral leishmaniasis (VL in Latin America, well-designed studies to inform diagnosis, treatment and control interventions are scarce. Few observational studies address prognostic assessment in patients with VL. This study aimed to identify risk factors for death in children aged less than 15 years admitted for VL treatment in a referral center in northeast Brazil. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort, we reviewed 546 records of patients younger than 15 years admitted with the diagnosis of VL at the Instituto de Medicina Integral Professor Fernando Figueira between May 1996 and June 2006. Age ranged from 4 months to 13.7 years, and 275 (50% were male. There were 57 deaths, with a case-fatality rate of 10%. In multivariate logistic regression, the independent predictors of risk of dying from VL were (adjusted OR, 95% CI: mucosal bleeding (4.1, 1.3-13.4, jaundice (4.4, 1.7-11.2, dyspnea (2.8, 1.2-6.1, suspected or confirmed bacterial infections (2.7, 1.2-6.1, neutrophil count <500/mm³ (3.1, 1.4-6.9 and platelet count <50,000/mm³ (11.7, 5.4-25.1. A prognostic score was proposed and had satisfactory sensitivity (88.7% and specificity (78.5%. CONCLUSIONS/SIGNIFICANCE: Prognostic and severity markers can be useful to inform clinical decisions such as whether a child with VL can be safely treated in the local healthcare facility or would potentially benefit from transfer to referral centers where advanced life support facilities are available. High risk patients may benefit from interventions such as early use of extended-spectrum antibiotics or transfusion of blood products. These baseline risk-based supportive interventions should be assessed in clinical trials.

  7. Serum cytokine profile in the subclinical form of visceral leishmaniasis

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    Gama M.E.A.

    2004-01-01

    Full Text Available The factors determining the development or not of visceral leishmaniasis (VL have not been completely identified, but a Leishmania-specific cellular immune response seems to play a fundamental role in the final control of infection. Few studies are available regarding the production of cytokines in the subclinical form of VL, with only the production of IFN-g and TNF-a known. The aim of the present study was to identify immunological markers for the oligosymptomatic or subclinical form of VL. A prospective cohort study was conducted on 784 children aged 0 to 5 years from an endemic area in the State of Maranhão, Brazil, between January 1998 and December 2001. During 30 consecutive months of follow-up, 33 children developed the oligosymptomatic form of the disease and 12 the acute form. During the clinical manifestations, serum cytokine levels were determined in 27 oligosymptomatic children and in nine patients with the acute form using a quantitative sandwich enzyme immunoassay. In the subclinical form of VL, variable levels of IL-2 were detected in 52.3% of the children, IL-12 in 85.2%, IFN-g in 48.1%, IL-10 in 88.9%, and TNF-a in 100.0%, with the last two cytokines showing significantly lower levels than in the acute form. IL-4 was not detected in oligosymptomatic individuals. Multiple discriminant analysis used to determine the profile or combination of cytokines predominating in the subclinical form revealed both a Leishmania resistance (Th1 and susceptibility (Th2 profile. The detection of both Th1 and Th2 cytokine profiles explains the self-limited evolution accompanied by the discrete alterations observed for the subclinical form of VL.

  8. Eco-epidemiology of visceral leishmaniasis in Ethiopia.

    Science.gov (United States)

    Gadisa, Endalamaw; Tsegaw, Teshome; Abera, Adugna; Elnaiem, Dia-Eldin; den Boer, Margriet; Aseffa, Abraham; Jorge, Alvar

    2015-07-19

    Visceral leishmaniasis (VL, Kala-azar) is one of the growing public health challenges in Ethiopia with over 3.2 million people at risk and estimated up to 4000 new cases per year. Historically, VL was known as the diseases of the lowlanders; in the lower and upper Kola agro-ecological zones of Ethiopia. The 2005-07 out breaks in highlands of Libo Kemkem and Fogera, in the Woina Degas, that affected thousands and claimed the life of hundreds misdiagnosed as drug resistance malaria marked that VL is no more the problem of the lowlanders. The Kola (lower and upper) and the Woina Dega are the most productive agroecological zones, supporting both the ongoing and planned expansions of large or small scale agriculture and/or agriculture based industries. Thus, the (re)emergence of VL is not only a public health and social problem but also have a direct implication on the country's economy and further development. Thus is high time for its control and/or elimination. Yet, the available data seem incomplete to plan for a cost-effective and efficient VL control strategy: there is a need to update data on vector behaviour in specific ecosystems and the roles of domestic animals need to be ascertained. The effectiveness and social acceptability of available vector control tools need be evaluated. There is a need for identifying animal reservoir(s), or establish the absence of zoonosis in Ethiopia. The planning of prevention of (re)emergence and spread of VL to areas adjacent to endemic foci need be supported with information from spatio-temporal mapping. In affected communities, available data showed that their knowledge about VL is generally very low. Thus, well designed studies to identify risk factors, as well as better tools for social mobilization with the understanding of their knowledge, aptitude and practice towards VL are necessary.

  9. 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

  10. Visceral leishmaniasis treatment outcome and its determinants in northwest Ethiopia.

    Science.gov (United States)

    Welay, Getachew Mebrahtu; Alene, Kefyalew Addis; Dachew, Berihun Assefa

    2016-01-01

    Poor treatment outcomes of visceral leishmaniasis (VL) are responsible for the high mortality rate of this condition in resource-limited settings such as Ethiopia. This study aimed to identify the proportion of poor VL treatment outcomes in northwest Ethiopia and to evaluate the determinants associated with poor outcomes. A hospital-based retrospective study was conducted among 595 VL patients who were admitted to Kahsay Abera Hospital in northwest Ethiopia from October 2010 to April 2013. Data were entered into Epi Info version 7.0 and exported to SPSS version 20 for analysis. Bivariate and multivariate logistic regression models were fitted to identify the determinants of VL treatment outcomes. Adjusted odds ratio (aORs) with 95% confidence intervals (CIs) were used, and p -values <0.05 were considered to indicate statistical significance. The proportion of poor treatment outcomes was 23.7%. Late diagnosis (≥29 days) (aOR, 4.34; 95% CI, 2.22 to 8.46), severe illness at admission (inability to walk) (aOR, 1.63; 95% CI, 1.06 to 2.40) and coinfection with VL and human immunodeficiency virus (HIV) (aOR, 2.72; 95% CI, 1.40 to 5.20) were found to be determinants of poor VL treatment outcomes. Poor treatment outcomes, such as death, treatment failure, and non-adherence, were found to be common. Special attention must be paid to severely ill and VL/HIV-coinfected patients. To improve VL treatment outcomes, the early diagnosis and treatment of VL patients is recommended.

  11. Cost of Pediatric Visceral Leishmaniasis Care in Morocco.

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    Nabil Tachfouti

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

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

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    Anette Stauch

    2011-11-01

    Full Text Available 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.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.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.

  13. Immunity to Visceral Leishmaniasis Using Genetically Defined Live-Attenuated Parasites

    Science.gov (United States)

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Gannavaram, Sreenivas; Lakhal-Naouar, Ines; Duncan, Robert; Salotra, Poonam; Nakhasi, Hira L.

    2012-01-01

    Leishmaniasis is a protozoan parasitic disease endemic to the tropical and subtropical regions of the world, with three major clinical forms, self-healing cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). Drug treatments are expensive and often result in the development of drug resistance. No vaccine is available against leishmaniasis. Subunit Leishmania vaccine immunization in animal models has shown some efficacy but little or none in humans. However, individuals who recover from natural infection are protected from reinfection and develop life-long protection, suggesting that infection may be a prerequisite for immunological memory. Thus, genetically altered live-attenuated parasites with controlled infectivity could achieve such memory. In this paper, we discuss development and characteristics of genetically altered, live-attenuated Leishmania donovani parasites and their possible use as vaccine candidates against VL. In addition, we discuss the challenges and other considerations in the use of live-attenuated parasites. PMID:21912560

  14. Immunity to Visceral Leishmaniasis Using Genetically Defined Live-Attenuated Parasites

    Directory of Open Access Journals (Sweden)

    Angamuthu Selvapandiyan

    2012-01-01

    Full Text Available Leishmaniasis is a protozoan parasitic disease endemic to the tropical and subtropical regions of the world, with three major clinical forms, self-healing cutaneous leishmaniasis (CL, mucocutaneous leishmaniasis (MCL, and visceral leishmaniasis (VL. Drug treatments are expensive and often result in the development of drug resistance. No vaccine is available against leishmaniasis. Subunit Leishmania vaccine immunization in animal models has shown some efficacy but little or none in humans. However, individuals who recover from natural infection are protected from reinfection and develop life-long protection, suggesting that infection may be a prerequisite for immunological memory. Thus, genetically altered live-attenuated parasites with controlled infectivity could achieve such memory. In this paper, we discuss development and characteristics of genetically altered, live-attenuated Leishmania donovani parasites and their possible use as vaccine candidates against VL. In addition, we discuss the challenges and other considerations in the use of live-attenuated parasites.

  15. 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...

  16. Leishmaniasis in Turkey: Visceral and cutaneous leishmaniasis caused by Leishmania donovani in Turkey.

    Science.gov (United States)

    Özbilgin, Ahmet; Harman, Mehmet; Karakuş, Mehmet; Bart, Aldert; Töz, Seray; Kurt, Özgür; Çavuş, İbrahim; Polat, Erdal; Gündüz, Cumhur; Van Gool, Tom; Özbel, Yusuf

    2017-09-01

    In Turkey, the main causative agents are Leishmania tropica (L. tropica) and Leishmania infantum (L. infantum) for cutaneous leishmaniasis (CL) and L. infantum for visceral leishmaniasis (VL). In this study, we investigated leishmaniasis cases caused by L. donovani and established animal models for understanding its tropism in in vivo conditions. Clinical samples (lesion aspirations and bone marrow) obtained from CL/VL patients were investigated using parasitological (smear/NNN) and DNA-based techniques. For species identification, a real time ITS1-PCR was performed using isolates and results were confirmed by hsp70 PCR-N/sequencing and cpb gene PCR/sequencing in order to reveal Leishmania donovani and Leishmania infantum discrimination. Clinical materials from CL and VL patients were also inoculated into two experimental groups (Group CL and Group VL) of Balb/C mice intraperitoneally for creating clinical picture of Turkish L. donovani strains. After 45days, the samples from visible sores of the skin were taken, and spleens and livers were removed. Measurements of the internal organs were done and touch preparations were prepared for checking the presence of amastigotes. The strains were isolated from all patients and amastigotes were seen in all smears of the patients, and then isolates were immediately stored in liquid nitrogen. In real time ITS1-PCR, the melting temperatures of all samples were out of range of L. infantum, L. tropica and L. major. Sequencing of hsp70 PCR-N showed that all isolates highly identical to previously submitted L. donovani sequences in GenBank, and cpb gene sequencing showed five isolates had longer cpbF allele, whereas one isolate contained a mixed sequence of both cpbF and cpbE. All mice in both experimental groups became infected. Compared to controls, the length and width of both liver and spleen were significantly elevated (pTurkey. Animal models using clinical samples were successfully established and important clinical

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

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    Angelita F Druzian

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

  18. 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.

  19. Culling dogs in scenarios of imperfect control: realistic impact on the prevalence of canine visceral leishmaniasis.

    Science.gov (United States)

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

    2013-01-01

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

  20. Culling dogs in scenarios of imperfect control: realistic impact on the prevalence of canine visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Danielle N C C Costa

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

  1. Immunotherapeutic Potential of Eugenol Emulsion in Experimental Visceral Leishmaniasis.

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    Mohammad Islamuddin

    2016-10-01

    Full Text Available The therapy of visceral leishmaniasis (VL is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in HIV-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (CMI. Thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. Several plant-derived compounds have been found to exert leishmanicidal activity via immunomodulation. In this direction, we investigated the antileishmanial activity of eugenol emulsion (EE, complemented with its immunomodulatory and therapeutic efficacy in murine model of VL.Oil-in-water emulsion of eugenol (EE was prepared and size measured by dynamic light scattering (DLS. EE exhibited significant leishmanicidal activity with 50% inhibitory concentration of 8.43±0.96 μg ml-1 and 5.05±1.72 μg ml─1, respectively against the promastigotes and intracellular amastigotes of Leishmania donovani. For in vivo effectiveness, EE was administered intraperitoneally (25, 50 and 75 mg/kg b.w./day for 10 days to 8 week-infected BALB/c mice. The cytotoxicity of EE was assessed in RAW 264.7 macrophages as well as in naive mice. EE induced a significant drop in hepatic and splenic parasite burdens as well as diminution in spleen and liver weights 10 days post-treatment, with augmentation of 24h-delayed type hypersensitivity (DTH response and high IgG2a:IgG1, mirroring induction of CMI. Enhanced IFN-γ and IL-2 levels, with fall in disease-associated Th2 cytokines (IL-4 and IL-10 detected by flow cytometric bead-based array, substantiated the Th1 immune signature. Lymphoproliferation and nitric oxide release were significantly elevated upon antigen revoke in vitro. The immune-stimulatory activity of EE was further corroborated by expansion of IFN-γ producing CD4+ and CD8+ splenic T lymphocytes and up-regulation of CD80 and CD86 on

  2. Mathematical analysis of a model for zoonotic visceral leishmaniasis

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    Nafiu Hussaini

    2017-11-01

    Full Text Available Zoonotic visceral leishmaniasis (ZVL, caused by the protozoan parasite Leishmania infantum and transmitted to humans and reservoir hosts by female sandflies, is endemic in many parts of the world (notably in Africa, Asia and the Mediterranean. This study presents a new mathematical model for assessing the transmission dynamics of ZVL in human and non-human animal reservoir populations. The model undergoes the usual phenomenon of backward bifurcation exhibited by similar vector-borne disease transmission models. In the absence of such phenomenon (which is shown to arise due to the disease-induced mortality in the host populations, the nontrivial disease-free equilibrium of the model is shown to be globally-asymptotically stable when the associated reproduction number of the model is less than unity. Using case and demographic data relevant to ZVL dynamics in Arac̣atuba municipality of Brazil, it is shown, for the default case when systemic insecticide-based drugs are not used to treat infected reservoir hosts, that the associated reproduction number of the model (ℛ0 ranges from 0.3 to 1.4, with a mean of ℛ0=0.85. Furthermore, when the effect of such drug treatment is explicitly incorporated in the model (i.e., accounting for the additional larval and sandfly mortality, following feeding on the treated reservoirs, the range of ℛ0 decreases to ℛ0∈[0.1,0.6], with a mean of ℛ0=0.35 (this significantly increases the prospect of the effective control or elimination of the disease. Thus, ZVL transmission models (in communities where such treatment strategy is implemented that do not explicitly incorporate the effect of such treatment may be over-estimating the disease burden (as measured in terms of ℛ0 in the community. It is shown that ℛ0 is more sensitive to increases in sandfly lifespan than that of the animal reservoir (so, a strategy that focuses on reducing sandflies, rather than the animal reservoir (e.g., via culling, may be

  3. 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

  4. Immunotherapeutic Potential of Eugenol Emulsion in Experimental Visceral Leishmaniasis.

    Science.gov (United States)

    Islamuddin, Mohammad; Chouhan, Garima; Want, Muzamil Yaqub; Ozbak, Hani A; Hemeg, Hassan A; Afrin, Farhat

    2016-10-01

    The therapy of visceral leishmaniasis (VL) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in HIV-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (CMI). Thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. Several plant-derived compounds have been found to exert leishmanicidal activity via immunomodulation. In this direction, we investigated the antileishmanial activity of eugenol emulsion (EE), complemented with its immunomodulatory and therapeutic efficacy in murine model of VL. Oil-in-water emulsion of eugenol (EE) was prepared and size measured by dynamic light scattering (DLS). EE exhibited significant leishmanicidal activity with 50% inhibitory concentration of 8.43±0.96 μg ml-1 and 5.05±1.72 μg ml─1, respectively against the promastigotes and intracellular amastigotes of Leishmania donovani. For in vivo effectiveness, EE was administered intraperitoneally (25, 50 and 75 mg/kg b.w./day for 10 days) to 8 week-infected BALB/c mice. The cytotoxicity of EE was assessed in RAW 264.7 macrophages as well as in naive mice. EE induced a significant drop in hepatic and splenic parasite burdens as well as diminution in spleen and liver weights 10 days post-treatment, with augmentation of 24h-delayed type hypersensitivity (DTH) response and high IgG2a:IgG1, mirroring induction of CMI. Enhanced IFN-γ and IL-2 levels, with fall in disease-associated Th2 cytokines (IL-4 and IL-10) detected by flow cytometric bead-based array, substantiated the Th1 immune signature. Lymphoproliferation and nitric oxide release were significantly elevated upon antigen revoke in vitro. The immune-stimulatory activity of EE was further corroborated by expansion of IFN-γ producing CD4+ and CD8+ splenic T lymphocytes and up-regulation of CD80 and CD86 on peritoneal

  5. Use of PCR on lymph-node sample as test of cure of visceral leishmaniasis

    NARCIS (Netherlands)

    Osman, O. F.; Kager, P. A.; Zijlstra, E. E.; El-Hassan, A. M.; Oskam, L.

    1997-01-01

    When the polymerase chain reaction (PCR) was used to test lymph-node aspirates from 35 patients from eastern Sudan, who had had visceral leishmaniasis but were believed cured, leishmanial DNA was detected in samples from 14 of the patients. There were no significant differences between the

  6. Experimental Evaluation of Second-Line Oral Treatments of Visceral Leishmaniasis Caused by Leishmania infantum

    OpenAIRE

    Gangneux, Jean-Pierre; Dullin, Michael; Sulahian, Annie; Garin, Yves Jean-Francois; Derouin, Francis

    1999-01-01

    In a murine model of Leishmania infantum visceral leishmaniasis, metronidazole, ketoconazole, fluconazole, itraconazole, and terbinafine were less effective than antimonial agents in reducing hepatic parasite load. Ketoconazole potentiated the effect of meglumine antimoniate reference therapy through its marked activity against spleen infection.

  7. First Report of Leishmania infantum in French Guiana: Canine Visceral Leishmaniasis Imported from the Old World

    OpenAIRE

    Rotureau, Brice; Ravel, Christophe; Aznar, Christine; Carme, Bernard; Dedet, Jean-Pierre

    2006-01-01

    The first two cases of canine visceral leishmaniasis in French Guiana are described. One infected dog was most probably imported from France. A second dog was then infected with Leishmania infantum in French Guiana. These observations exemplify the intercontinental transportation theory for L. infantum.

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

    NARCIS (Netherlands)

    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; Khanal, Basudha; Das, Murari; Oliveira, Edward; de Assis, Tália Machado; Costa, Dorcas Lamounier; Bhaskar, Khondaker Rifathassan; Huda, M. Mamun; Hassan, Mukidul; Abdoun, Asim Osman; Awad, Aymen; Osman, Mohamed; Prajapati, Dinesh Kumar; Gidwani, Kamlesh; Tiwary, Puja; Paniago, Anamaria Mello Miranda; Sanchez, Maria Carmen Arroyo; Celeste, Beatriz Julieta; Jacquet, Diane; Magiri, Charles; Muia, A.; Kesusu, J.; Ageed, Al Farazdag; Galal, Nuha; Osman, Osman Salih; Gupta, A. K.; Bimal, Afrad S.; Das, V. N. R.

    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

  9. First report of Leishmania infantum in French Guiana: canine visceral leishmaniasis imported from the Old World.

    Science.gov (United States)

    Rotureau, Brice; Ravel, Christophe; Aznar, Christine; Carme, Bernard; Dedet, Jean-Pierre

    2006-03-01

    The first two cases of canine visceral leishmaniasis in French Guiana are described. One infected dog was most probably imported from France. A second dog was then infected with Leishmania infantum in French Guiana. These observations exemplify the intercontinental transportation theory for L. infantum.

  10. Splenomegaly in Baringo District, Kenya, an area endemic for visceral leishmaniasis and malaria

    NARCIS (Netherlands)

    Schaefer, K. U.; Khan, B.; Gachihi, G. S.; Kager, P. A.; Muller, A. S.; Verhave, J. P.; McNeill, K. M.

    1995-01-01

    The relationship between splenomegaly and visceral leishmaniasis (VL) was investigated during a cross-sectional study in 2,941 individuals in Baringo District, Kenya, where both malaria and VL are endemic. Spleen size was correlated with presence of malaria parasites in thick blood films and with

  11. A case report of visceral leishmaniasis in red fox (Vulpes vulpes)

    African Journals Online (AJOL)

    ajl yemi

    2011-12-30

    Dec 30, 2011 ... Visceral leishmaniasis has been described in dogs and other members of the Canidae family in the ... too many seropositive dogs exist in the endemic areas and anti vector measures have been largely .... denaturation at 94°C for 4 min followed by 30 cycles of denaturation at 94°C for 1 min, annealing at ...

  12. 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 was a...

  13. 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...

  14. 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...

  15. 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....

  16. In vitro and in vivo resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from patients with visceral leishmaniasis.

    Science.gov (United States)

    Faraut-Gambarelli, F; Piarroux, R; Deniau, M; Giusiano, B; Marty, P; Michel, G; Faugère, B; Dumon, H

    1997-04-01

    Primary and secondary unresponsiveness to meglumine has long been described in human visceral leishmaniasis. However, no studies have been performed to elucidate if these therapeutic failures were due to strain variability in meglumine sensitivity or were related to host factors. We have studied the in vitro sensitivity of 37 strains of Leishmania infantum isolated from 23 patients (11 human immunodeficiency virus-infected and 12 immunocompetent patients) with visceral leishmaniasis. Sensitivity tests were performed by infecting murine macrophages with Leishmania parasites and culturing them in medium containing different concentrations of meglumine. For each test we calculated a 50% effective dose (ED50) corresponding to the meglumine concentration at which 50% of the Leishmania parasites survived. In vitro results were strongly correlated to immediate clinical outcome. All strains requiring an ED50 of >70 microg/ml were related to therapeutic failures, whereas all strains requiring an ED50 of <40 microg/ml corresponded to an initial efficiency of meglumine. Among those patients who were initially improved, relapses occurred in all immunocompromised patients and in most immunocompetent patients who had a short duration of treatment (15 days). Finally, we found that in vitro sensitivity of strains decreased progressively in relapsing patients treated with meglumine. Consequently, the physician may be encouraged to alternate meglumine with other treatments such as amphotericin B or pentamidine, especially in the case of relapsing patients.

  17. 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

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

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    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

  19. Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients

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    Wim Adriaensen

    2018-01-01

    Full Text Available Patients with visceral leishmaniasis (VL–human immunodeficiency virus (HIV coinfection experience increased drug toxicity and treatment failure rates compared to VL patients, with more frequent VL relapse and death. In the era of VL elimination strategies, HIV coinfection is progressively becoming a key challenge, because HIV-coinfected patients respond poorly to conventional VL treatment and play an important role in parasite transmission. With limited chemotherapeutic options and a paucity of novel anti-parasitic drugs, new interventions that target host immunity may offer an effective alternative. In this review, we first summarize current views on how VL immunopathology is significantly affected by HIV coinfection. We then review current clinical and promising preclinical immunomodulatory interventions in the field of VL and discuss how these may operate in the context of a concurrent HIV infection. Caveats are formulated as these interventions may unpredictably impact the delicate balance between boosting of beneficial VL-specific responses and deleterious immune activation/hyperinflammation, activation of latent provirus or increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a target molecule and a more detailed account of the immunological status induced by the coinfection as well as surrogate markers of cure and protection are still required. We do, however, argue that virologically suppressed VL patients with a recovered immune system, in whom effective antiretroviral therapy alone is not able to restore protective immunity, can be considered a relevant target group for an immunomodulatory intervention. Finally, we provide perspectives on the translation of novel theories on synergistic immune cell cross-talk into an effective treatment strategy for VL–HIV-coinfected patients.

  20. 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

  1. 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; Torres-Santos, Eduardo Caio

    2016-06-01

    Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. HIV/AIDS-associated visceral leishmaniasis in patients from an endemic area in Central-west Brazil

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    Priscilla Alexandrino-de-Oliveira

    2010-08-01

    Full Text Available An increase in morbidity associated with visceral leishmaniasis (VL in human immunodeficiency virus (HIV/AIDS patients has been described in Africa and the Mediterranean. Despite the high endemicity of VL and HIV-1/AIDS in Brazil, this association has not been thoroughly investigated. Our aim was to evaluate the epidemiologic and clinical characteristics of VL-HIV-1/AIDS cases from Central-west [Mato Grosso do Sul (MS] Brazil. Medical records of 23 VL-HIV-1/AIDS patients were reviewed. Patients were predominantly adult males (87% and 34.8% of the patients were intravenous drug users (IVDU. Leishmaniasis was the first opportunistic infection in 60% of the HIV-1 patients. Fever occurred in all patients, although splenomegaly and hepatomegaly were absent in 21.7% of the cases. CD4+ T-cell counts were below 200 cells/mm³ in 80% of the cases and the counts did not increase after clinical remission despite antiretroviral therapy. The first drug chosen to treat the cases was antimonial, but the therapeutic regimen was altered to amphotericin B in 12 of 17 cases due to side effects. Relapses were reported in 56.5% of the patients. IVDU may constitute an important risk factor for the transmission of both diseases in MS. VL-HIV-1/AIDS patients in MS share similar clinical characteristics as those from other endemic regions worldwide. Thus, these findings are critical for improving the surveillance of VL-HIV/AIDS patients.

  3. Early efficacy of liposomal amphotericin B in the treatment of visceral leishmaniasis.

    Science.gov (United States)

    Castagnola, E; Davidson, R N; Fiore, P; Tasso, L; Rossi, G; Mangraviti, S; Di Martino, L; Scotti, S; Cascio, A; Pempinello, R; Gradoni, L; Giacchino, R

    1996-01-01

    The rapidity and efficacy of a short course of liposomal amphotericin B was evaluated in 29 children affected by visceral leishmaniasis (Leishmania infantum). Their overall health status was assessed using the prognostic inflammatory and nutritional index (PINI), and their haematological status by the reticulocyte count and haemoglobin blood levels. All these quantities were measured on day 0, and 3 and 10 d after starting therapy. A significant decrease of inflammatory signs, associated with an improved reticulocyte count, was recorded after 3 d of therapy. A significant increase of haemoglobin levels was also observed 10 d after the start of treatment. The early reduction of inflammatory signs and the improvement of bone marrow function in most patients confirmed the validity of amphotericin B therapy. The PINI score is helpful in assessing the severity of visceral leishmaniasis and the follow-up of its treatment.

  4. 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. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. 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.

  6. Leishmania infantum FML pulsed-dendritic cells induce a protective immune response in murine visceral leishmaniasis.

    Science.gov (United States)

    Foroughi-Parvar, Faeze; Hatam, Gholam-Reza; Sarkari, Bahador; Kamali-Sarvestani, Eskandar

    2015-01-01

    To investigate the efficacy of FML loaded dendritic cells (DCs) in protection against visceral leishmaniasis. Mice were immunized with FML- or soluble Leishmania antigen-loaded DCs as well as FML or soluble Leishmania antigen in saponin and challenged with parasite. The levels of cytokines before and after challenge were detected by ELISA. Parasite burden (total Leishman-Donovan unit) was determined after parasite challenge. FML-saponin induced the highest IFN-γ/IL-4 ratio among vaccinated groups, though this ratio was higher in FML-loaded DCs group subsequent to challenge with Leishmania infantum. Moreover, the greatest reduction in parasite number was detected in mice vaccinated with FML-loaded DCs compared with phosphate-buffered saline-treated mice (p = 0.002). FML-loaded DCs are one of the promising tools for protection against murine visceral leishmaniasis.

  7. 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 was a...... was an 18 month old previously healthy boy, infected in Southern Spain. The symptomtology, diagnosis and treatment of the disease are discussed and it is stressed that serological diagnostic tests have limited value in HIV positive patients.......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...

  8. 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.

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

    OpenAIRE

    Távora,Lara Gurgel Fernandes; Nogueira, Marina Bizerril; Gomes, Sofia Teixeira

    2015-01-01

    ABSTRACT Since the beginning of the HIV burden, Visceral Leishmaniasis (VL)/HIV co-infection has been diagnosed not only in areas where VL is endemic (Latin America, India, Asia, Southern Europe), but also in North America, were it is considered an opportunistic disease. Clinical presentation, diagnostic tests sensitivity and treatment response in this population differs from VL alone. OBJECTIVES: To evaluate factors related to an unfavorable outcome in patients with VL/HIV diagnosis in a r...

  10. 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.

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

    Science.gov (United States)

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

    2011-01-01

    The persistence of anti-Leishmania donovani antibodies in past visceral leishmaniasis (VL) cases was retrospectively assessed by means of the direct agglutination test (DAT) and the rK39 enzyme-linked immunosorbent assay (ELISA). Antibody titers remained high for an extended period of time in past cases of VL. These results highlight the need to carefully elicit the history of patients with VL symptoms. PMID:21159922

  12. 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.

  13. 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.

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

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    S Molaie

    2010-10-01

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

  15. Assessment of the electrocardiogram in dogs with visceral leishmaniasis

    OpenAIRE

    Sousa, Marlos G.; Carareto, Roberta; Silva, Jeanna G.; Oliveira, Juliana

    2013-01-01

    As myocarditis and arrhythmias have been shown to occur in both human beings and dogs with leishmaniasis, electrocardiograms of 105 dogs serologically positive for this disease were assessed for rhythm disturbances and changes in ECG waves. A few expressive alterations were seen, including sinus arrest, right bundle branch block, and atrial premature beats in 14.3%, 4.8%, and 4.8% of the studied subjects, respectively. Also, the analysis of ECG waves showed changes suggestive of left atrium a...

  16. Pediatric Visceral Leishmaniasis in Albania: A Retrospective Analysis of 1,210 Consecutive Hospitalized Patients (1995–2009)

    Science.gov (United States)

    Petrela, Raida; Kuneshka, Loreta; Foto, Eli; Zavalani, Ferit; Gradoni, Luigi

    2010-01-01

    Background Little information is available about infantile visceral leishmaniasis (VL) in Albania as regards incidence, diagnosis and management of the disease. Methodology/Principal Findings Demographic data, clinical and laboratory features and therapeutic findings were considered in children admitted to University Hospital of Tirana from 1995 to 2009, and diagnosed as having VL. The diagnosis was based on bone-marrow microscopy/culture in 77.5% of patients, serology in 16.1%, and ex juvantibus in 6.4%. A total of 1,210 children were considered, of whom 74% came from urbanized areas. All patients were in the age range 0–14 years, with a median of 4 years. Hepatosplenomegaly was recorded in 100%, fever in 95.4% and moderate to severe anemia in 88% of cases. Concomitant conditions were frequent: 84% had bronchopneumonia; diarrhea was present in 27%, with acute manifestations in 5%; 3% had salmonellosis. First-line therapy was meglumine antimoniate for all patients, given at the standard Sbv dosage of 20 mg/kg/day for 21 to 28 days. Two children died under treatment, one of sepsis, the other of acute renal impairment. There were no cases of primary unresponsiveness to treatment, and only 8 (0.67%) relapsed within 6–12 months after therapy. These patients have been re-treated with liposomal amphotericin B, with successful cure. Conclusions Visceral leishmaniasis in pediatric age is relatively frequent in Albania; therefore an improvement is warranted of a disease-specific surveillance system in this country, especially as regards diagnosis. Despite recent reports on decreased responses to antimonial drugs of patients with Mediterranean VL, meglumine antimoniate treatment appears to be still highly effective in Albania. PMID:20838650

  17. Pediatric visceral leishmaniasis in Albania: a retrospective analysis of 1,210 consecutive hospitalized patients (1995-2009).

    Science.gov (United States)

    Petrela, Raida; Kuneshka, Loreta; Foto, Eli; Zavalani, Ferit; Gradoni, Luigi

    2010-09-07

    Little information is available about infantile visceral leishmaniasis (VL) in Albania as regards incidence, diagnosis and management of the disease. Demographic data, clinical and laboratory features and therapeutic findings were considered in children admitted to University Hospital of Tirana from 1995 to 2009, and diagnosed as having VL. The diagnosis was based on bone-marrow microscopy/culture in 77.5% of patients, serology in 16.1%, and ex juvantibus in 6.4%. A total of 1,210 children were considered, of whom 74% came from urbanized areas. All patients were in the age range 0-14 years, with a median of 4 years. Hepatosplenomegaly was recorded in 100%, fever in 95.4% and moderate to severe anemia in 88% of cases. Concomitant conditions were frequent: 84% had bronchopneumonia; diarrhea was present in 27%, with acute manifestations in 5%; 3% had salmonellosis. First-line therapy was meglumine antimoniate for all patients, given at the standard Sb(v) dosage of 20 mg/kg/day for 21 to 28 days. Two children died under treatment, one of sepsis, the other of acute renal impairment. There were no cases of primary unresponsiveness to treatment, and only 8 (0.67%) relapsed within 6-12 months after therapy. These patients have been re-treated with liposomal amphotericin B, with successful cure. Visceral leishmaniasis in pediatric age is relatively frequent in Albania; therefore an improvement is warranted of a disease-specific surveillance system in this country, especially as regards diagnosis. Despite recent reports on decreased responses to antimonial drugs of patients with Mediterranean VL, meglumine antimoniate treatment appears to be still highly effective in Albania.

  18. Vulnerability to the transmission of human visceral leishmaniasis in a Brazilian urban area.

    Science.gov (United States)

    Toledo, Celina Roma Sánchez de; Almeida, Andréa Sobral de; Chaves, Sergio Augusto de Miranda; Sabroza, Paulo Chagastelles; Toledo, Luciano Medeiros; Caldas, Jefferson Pereira

    2017-05-15

    To analyze the determinants for the occurrence of human visceral leishmaniasis linked to the conditions of vulnerability. This is an ecological study, whose spatial analysis unit was the Territorial Analysis Unit in Araguaína, State of Tocantins, Brazil, from 2007 to 2012. We have carried out an analysis of the sociodemographic and urban infrastructure situation of the municipality. Normalized primary indicators were calculated and used to construct the indicators of vulnerability of the social structure, household structure, and urban infrastructure. From them, we have composed a vulnerability index. Kernel density estimation was used to evaluate the density of cases of human visceral leishmaniasis, based on the coordinates of the cases. Bivariate global Moran's I was used to verify the existence of spatial autocorrelation between the incidence of human visceral leishmaniasis and the indicators and index of vulnerability. Bivariate local Moran's I was used to identify spatial clusters. We have observed a pattern of centrifugal spread of human visceral leishmaniasis in the municipality, where outbreaks of the disease have progressively reached central and peri-urban areas. There has been no correlation between higher incidences of human visceral leishmaniasis and worse living conditions. Statistically significant clusters have been observed between the incidences of human visceral leishmaniasis in both periods analyzed (2007 to 2009 and 2010 to 2012) and the indicators and index of vulnerability. The environment in circumscribed areas helps as protection factor or increases the local vulnerability to the occurrence of human visceral leishmaniasis. The use of methodology that analyzes the conditions of life of the population and the spatial distribution of human visceral leishmaniasis is essential to identify the most vulnerable areas to the spread/maintenance of the disease. Analisar determinantes para a ocorrência da leishmaniose visceral humana vinculados

  19. Visceral leishmaniasis in a rheumatoid arthritis patient receiving methotrexate.

    Science.gov (United States)

    Reina, Delia; Cerdà, Dacia; Güell, Elena; Martínez Montauti, Joaquín; Pineda, Antonio; Corominas, Hèctor

    Patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis. As L. infantum is endemic in the Mediterranean region, it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia. An early diagnosis based on a high suspicion can prevent a fatal outcome. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  20. 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.

  1. Travelers' Health: Leishmaniasis, Cutaneous

    Science.gov (United States)

    ... Legionnaires’ Disease & Pontiac Fever) Chapter 3 - Leishmaniasis, Visceral Leishmaniasis, Cutaneous Barbara L. Herwaldt, Alan J. Magill Leishmaniasis is a parasitic disease found in parts of ...

  2. 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

  3. Evaluation of a Novel Herbal Immunomodulator Drug (IMOD) in Treatment of Experimental Canine Visceral leishmaniasis.

    Science.gov (United States)

    Malmasi, Abdolali; Ziaie Ardestani, Bijan; Mohebali, Mehdi; Akhoundi, Behnaz; Ziaie, Shadi; Masoudifard, Majid; Khorram Khorshid, Hamidreza; Nasiri, Mehdi; Bayanolhagh, Saeed; Mostafavi, Ehsan; Delrobai, Moin; Siavashi, Vahid

    2014-01-01

    Toxicity and drug resistance against pentavalent antimonials, medications of choice in treatment of leishmaniasis for more than 5 decades, have become important subjects globally. This study was a randomized, open labeled trial that was designed to determine efficacy and safety of IMOD as a novel herbal immunomodulator drug for treatment of canine visceral leishmaniasis (CVL). Twenty healthy mongrel dogs were infected with Iranian strain of L. Infantum amastigotes and randomly divided to 5 groups with four animals for each included on: I: negative control (non-infected) II: Glucantime® III: Glucantime® plus IMOD (immune-chemotherapy) IV: IMOD and V: positive control (non-treated). Physical examination, hematological, biochemical, serological, parasitological, pathological and imaging evaluations were performed pre-/post- interventions every month for 3 months. Comparing with control groups (I&V), immune-chemotherapy group (Glucantime® plus IMOD) showed significantly higher efficacy in resolving the clinical signs and hematobiochemistry factors. Based on our results, using IMOD in combination with meglumine antimoniate (Glucantime®) has significantly improved CVL than the latter drug alone. So, it seems this new herbal medicine is useful as adjuvant therapy for canine visceral leishmaniasis.

  4. Preliminary survey of domestic animal visceral leishmaniasis and risk factors in north-west Ethiopia.

    Science.gov (United States)

    Kenubih, Ambaye; Dagnachew, Shimelis; Almaw, Gizat; Abebe, Tamerat; Takele, Yegnasew; Hailu, Asrat; Lemma, Wessensegad

    2015-02-01

    After the epidemics of L. donovani complex in 2004/05 in human patients, to investigate the presence of antibodies against L. donovani in domestic animals in north-west Ethiopia. Two hundred and three domestic animals were screened. Serum and biopsy samples were collected. A modified direct agglutination test (DAT) for canine reservoirs was used to screen serum samples at ≥ 1:320 cut-off titre. Giemsa stain and culture on Novy macNeal Nicolae (NNN) media were used for biopsy samples. Pre-tested questionnaires were used to elicit information on potential risk factors. Antibody against L. donovani in domestic animals was detected in 30.5% of animals. The highest seropositivity rates were 41.9% in cattle, 40% in dogs, 33.3% in donkeys, 10% in goats and 4.8% in sheep. No Leishmania parasite was isolated from spleen, liver, skin snip and exudates, bone marrow or lymph node of dogs. Dogs owned by households with history of kala-azar treatment and humans sharing the house with cattle were more affected by visceral leishmaniasis (P < 0.05). This study showed a high serological prevalence of leishmaniasis in domestic animals. Their role in the epidemiology of visceral leishmaniasis remains unclear. © 2014 John Wiley & Sons Ltd.

  5. 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.

  6. 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

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

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    Filip Meheus

    2010-09-01

    Full Text Available 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.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.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 available.

  8. Sustaining visceral leishmaniasis elimination in Bangladesh - Could a policy brief help?

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    Alyssa Fitzpatrick

    2017-12-01

    Full Text Available Bangladesh has made significant progress towards elimination of visceral leishmaniasis, and is on track to achieve its target of less than one case per 10,000 inhabitants in each subdistrict in 2017. As the incidence of disease falls, it is likely that the political capital and financial resources dedicated towards the elimination of visceral leishmaniasis may decrease, raising the prospect of disease resurgence. Policy memos may play a crucial role during the transition of the elimination plan from the 'attack' to the 'consolidation' and 'maintenance' phases, highlighting key stakeholders and areas where ongoing investment is crucial. An example of a policy brief is outlined in this paper. The background to the current elimination efforts is highlighted, with emphasis on remaining uncertainties including the impact of disease reservoirs and sustainable surveillance strategies. A stakeholder map is provided outlining the current and projected future activities of key bodies. Identification of key stakeholders subsequently frames the discussion of three key policy recommendations in the Bangladeshi context for the transition to the consolidation and maintenance phases of the elimination program. Recommendations include determining optimal vector control and surveillance strategies, shifting the emphasis towards horizontal integration of disease programs, and prioritising remaining research questions with a focus on operational and technical capacity. Achieving elimination is as much a political as a scientific question. Integrating the discussion of key stakeholders with policy priorities and the research agenda provides a novel insight into potential pathways forwards in the elimination of visceral leishmaniasis in Bangladesh and in the rest of the Indian subcontinent.

  9. 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.

  10. Evaluation of three recombinant Leishmania infantum antigens in human and canine visceral leishmaniasis diagnosis.

    Science.gov (United States)

    Fonseca, Aliani Moura; Faria, Angélica Rosa; Rodrigues, Fernandes Tenório Gomes; Nagem, Ronaldo Alves Pinto; Magalhães, Rubens Daniel Miserani; Cunha, João Luís Reis; Bartholomeu, Daniella Castanheira; de Andrade, Hélida Monteiro

    2014-09-01

    Visceral leishmaniasis (VL) is a neglected disease and is fatal if untreated. Dogs serve as reservoirs for Leishmania infantum (syn. L. chagasi) due to their susceptibility to infection and high skin parasitism. Therefore, VL control in Brazil involves the elimination of seropositive dogs, among other actions. However, the most frequently used serological tests have limitations regarding sensitivity and specificity. In this study, we have selected three Leishmania antigens (C1, C8 and C9) and have produced them as recombinant proteins using pET-28a-TEV vector and Escherichia coli BL-21 as expression system. When tested in ELISA with human samples, the C9 antigen was the one showing the most promising results, with 68% sensitivity and 78% specificity. When testing canine samples, the C1, C8 and C9 antigens showed a sensitivity range from 70% to 80% and specificity range from 60% to 90%. The C1 antigen presented higher sensitivity (80%) and the C8 antigen presented higher specificity (90%). Due to it, we decided to mix and test C1 and C8 antigens together, resulting in the C18 antigen. The mix also yielded high percentages of detected symptomatic and asymptomatic dogs however it did not improve the performance of the diagnostic. Comparison of our tests with the tests recommended by the Brazilian Ministry of Health revealed that our antigens' sensitivities and the percentage of detected asymptomatic dogs were much higher. Our results suggest that the C1, C8, C18 and C9 recombinant proteins are good antigens to diagnose canine visceral leishmaniasis and could potentially be used in screening tests. To diagnose human visceral leishmaniasis, the C9 antigen presented reasonable results, but more optimization must be performed for this antigen to provide better performance. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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    Santanu Biswas

    Full Text Available 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.

  12. Increasing potential risk for American visceral leishmaniasis in Amapá, Brazil

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    Thiago Vasconcelos dos Santos

    Full Text Available Abstract: INTRODUCTION: The present note discusses some evidence on the increasing potential risk for American visceral leishmaniasis (AVL transmission in the Northern Brazilian State of Amapá, the Guianan-Amazon biome. METHODS Early and present data about AVL were collected, including our recent entomological findings. RESULTS: The spread of the sand fly vector Lutzomyia longipalpis, and a sylvatic reservoir host, the crab-eating fox Cerdocyon thous in that region represents important findings related to the epidemiology of AVL in the Guianan-Amazon biome. CONCLUSIONS: These observations suggest that Brazilian authorities need to develop surveillance strategies in these risk areas.

  13. 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.

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

    Science.gov (United States)

    Pimentel, Danillo de Souza; Ramos, Rafael Antonio Nascimento; Santana, Marília de Andrade; Maia, Carina Scanoni; de Carvalho, Gílcia Aparecida; da Silva, Hernande Pereira; Alves, Leucio Câmara

    2015-01-01

    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. 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(r)Biogene). Of the 600 dogs tested, 19% (115/600) presented anti-L. infantum chagasi antibodies. Our data are important because canine infection is an important risk factor for the human disease.

  15. 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.

  16. 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...... was an 18 month old previously healthy boy, infected in Southern Spain. The symptomtology, diagnosis and treatment of the disease are discussed and it is stressed that serological diagnostic tests have limited value in HIV positive patients....

  17. [Additional evidence for the species composition of mosquitoes (Diptera, Psichodidae, Phlebotominae) in the visceral leishmaniasis foci of Uzbekistan].

    Science.gov (United States)

    Fatullaeva, A A; Kovalenko, D A; Baranets, M S; Ponirovskiĭ, E N

    2014-01-01

    The species composition of mosquitoes was studied in the foci of visceral leishmaniasis in the Navoiy and Samarkand Provinces of Uzbekistan. The human settlements where these observations were made were located at 1000-1200 m above sea level. Seven species: Phlebotomus sergenti, P. caucasicus, P. longiductus, P. papatasi, P. alexandri, Sergetomyia sumbarica, and S. grecovi were found. The predominant species was P. sergenti; P. longiductus was a vector for visceral leishmaniasis, which was present in all the collected samples. Bovine animal and small cattle yards were ascertained to be the hatching of mosquito eggs.

  18. 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

    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.

  19. Current clinical, laboratory, and treatment outcome characteristics of visceral leishmaniasis: results from a seven-year retrospective study in Greece.

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    Georgiadou, Sarah P; Stefos, Aggelos; Spanakos, Gregory; Skrimpas, Stergios; Makaritsis, Konstantinos; Sipsas, Nikolaos V; Dalekos, George N

    2015-05-01

    Visceral leishmaniasis (VL) is re-emerging in endemic areas. The epidemiological, clinical, laboratory, and treatment outcome characteristics in a large cohort of VL patients is described herein. The cases of 67 VL patients (57% male, mean age 56 years) treated in two Greek hospitals over the last 7 years were identified and evaluated retrospectively. Forty-six percent of patients reported contact with animals. Seventeen patients (25%) were immunocompromised, and 22% were co-infected with another pathogen. Sixty-four percent of patients had fever, 57% had weakness, 37% had sweats, 21% had weight loss, and 13% had a dry cough, while 6% developed haemophagocytic syndrome. The median duration of symptoms was 28 days. Fifty-eight percent of patients had splenomegaly, 49% had hepatomegaly, and 36% had lymphadenopathy. The diagnosis was established by positive PCR in peripheral blood (73%) and/or bone marrow specimens (34%). Sixty-one patients (91%) received liposomal amphotericin (L-AMB). Six patients (10%) did not respond or relapsed but were eventually cured after a second cycle of L-AMB. During a 6-month follow-up, the overall mortality was 9%, although none of these deaths was attributed to VL. VL is still a common disease in endemic areas, affecting immunocompetent and immunocompromised patients. Its diagnosis is challenging, and molecular techniques are valuable and helpful tools to achieve this. Treatment with L-AMB is safe and very effective. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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    Benoit Faucher

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

  1. Animal models for vaccine studies for visceral leishmaniasis.

    Science.gov (United States)

    Garg, Ravendra; Dube, Anuradha

    2006-03-01

    Visceral leishmaniases (VL) or kala-azar is the most dreaded and devastating amongst the various forms of leishmaniases. The disease, though localized in certain areas only, has gained immense importance because of high mortality rate, mainly in children. The parasite is responsible for a spectrum of clinical syndromes, which can, in most extreme cases, go from an asymptomatic infection to a fatal form of VL. Chemotherapeutic measures, alone are not sufficient to control and contain the disease. As an alternate strategy, vaccination is also under experimental and clinical trails. The situation unquestionably demands the use of proper screening system, rationale chemical synthesis, vaccine development and targeted vaccine delivery. Thus, development of an acceptable vaccine is not an easy task. While the factors, which determine clinical outcomes, are in part, a feature of the parasite, it is the nature of the host and its genetic make up and immune status that play crucial role. The prerequisite of reliable animal model is that it should have a considerably good correlation with the clinical situation and is expected to mimic the pathological features and immunological responses observed in humans when exposed to a variety of Leishmania spp. with different pathogenic characteristics. Many experimental animal models like rodents, dogs and monkeys have been developed, each with specific features, but none accurately reproduces what happens in humans. In addition to the nature of the host, the major difference between natural and experimental infections is the parasite inoculum; in natural conditions, the infected sand fly vector deposits a few hundred metacyclic promastigotes into the dermis of the host, whereas experimental infections are induced by the injection (subcutaneous or intravenous) of millions of promastigotes grown in axenic cultures in vitro or amastigotes recovered from infected spleens. In public health terms, VL is the disease of humans and dogs

  2. An experimental challenge model of visceral leishmaniasis by Leishmania donovani promastigotes in mice.

    Science.gov (United States)

    Katakura, Ken

    2016-10-01

    Although visceral leishmaniasis is a fatal disease in humans and dogs, the use of mouse models is important for obtaining a better understanding of the pathogenesis, immunity, and host-parasite interactions of this disease. Such models are also useful for the evaluation of vaccines and chemotherapies for treatment of visceral leishmaniasis. Here, we present our method of experimental inoculation of mice with Leishmania donovani promastigotes. Nutrient-enriched undefined media may be beneficial for laboratory maintenance of promastigotes for maintaining their virulence or infectivity in mice. With this method, we could preserve the infectivity of promastigote lines recovered from inoculated animals and use these lines for further in vivo experiments. Furthermore, the use of cryopreserved stabilates is highly recommended for the reproducibility of experiments. To assess a newly developed method for determination of parasite burden in infected animal tissues, initial comparison of parasite burden in the liver obtained in the classic Leishman-Donovan units (LDU) with values obtained from the new method is recommended. As an example, the association between parasite burden determined by LDU and real-time PCR assay targeting the leishmanial gp63 gene in the liver of mice is presented. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Rapid tests for the diagnosis of visceral leishmaniasis in patients with suspected disease

    Science.gov (United States)

    Boelaert, Marleen; Verdonck, Kristien; Menten, Joris; Sunyoto, Temmy; van Griensven, Johan; Chappuis, Francois; Rijal, Suman

    2014-01-01

    Background The diagnosis of visceral leishmaniasis (VL) in patients with fever and a large spleen relies on showing Leishmania parasites in tissue samples and on serological tests. Parasitological techniques are invasive, require sophisticated laboratories, consume time, or lack accuracy. Recently, rapid diagnostic tests that are easy to perform have become available. Objectives To determine the diagnostic accuracy of rapid tests for diagnosing VL in patients with suspected disease presenting at health services in endemic areas. Search methods We searched MEDLINE, EMBASE, LILACS, CIDG SR, CENTRAL, SCI-expanded, Medion, Arif, CCT, and the WHO trials register on 3 December 2013, without applying language or date limits. Selection criteria This review includes original, phase III, diagnostic accuracy studies of rapid tests in patients clinically suspected to have VL. As reference standards, we accepted: (1) direct smear or culture of spleen aspirate; (2) composite reference standard based on one or more of the following: parasitology, serology, or response to treatment; and (3) latent class analysis. Data collection and analysis Two review authors independently extracted data and assessed quality of included studies using the QUADAS-2 tool. Discrepancies were resolved by a third author. We carried out a meta-analysis to estimate sensitivity and specificity of rapid tests, using a bivariate normal model with a complementary log-log link function. We analysed each index test separately. As possible sources of heterogeneity, we explored: geographical area, commercial brand of index test, type of reference standard, disease prevalence, study size, and risk of bias (QUADAS-2). We also undertook a sensitivity analysis to assess the influence of imperfect reference standards. Main results Twenty-four studies containing information about five index tests (rK39 immunochromatographic test (ICT), KAtex latex agglutination test in urine, FAST agglutination test, rK26 ICT, and r

  4. 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

  5. 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.

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

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    Danielly Vieira Bortoletto

    2016-01-01

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

  7. Epidemiological Investigation of Asymptomatic Dogs with Leishmania Infection in Southwestern China Where Visceral Leishmaniasis is Intractable.

    Science.gov (United States)

    Zhao, Gui-Hua; Yin, Kun; Zhong, Wei-Xia; Xiao, Ting; Wei, Qing-Kuan; Cui, Yong; Liu, Gong-Zhen; Xu, Chao; Wang, Hong-Fa

    2016-12-01

    Heishui county, located in northwest Sichuan province, southwestern China, is an endemic area of zoonotic visceral leishmaniasis (VL) and is the most intractable area. VL is never destroyed in it. Asymptomatic dogs (Leishmania parasites have been diagnosed but clinically healthy) are considered to be a potential reservoir host in zoonotic VL area, and most can lead to infection of individuals, that is a new challenge for controlling VL in humans. The present study aimed to assess the Leishmania infection rate of asymptomatic dogs in Heishui county. Total 105 asymptomatic domestic dogs were gathered from 4 districts in Heishui county to investigate the infection rate with serological and molecular methods based on ELISA and kinetoplast minicircle DNA(kDNA) PCR, respectively. Out of 105 dogs, 44 (41.9%) were positive by more than 1 method; 21 (20.0%) were positive by ELISA, and 30 (28.6%) were positive by kDNA-PCR. Our study showed that Leishmania infection of domestic dogs which is clinically healthy is prevalent in the studied district, and the asymptomatic dogs infected by Leishmania may be the primary reason for the prevalence of visceral leishmaniasis in the area.

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

    Science.gov (United States)

    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.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Denise Amaro da SILVA

    2015-10-01

    Full Text Available 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.

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

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    Amanda Codeço de OLIVEIRA

    2015-08-01

    Full Text Available SUMMARY 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 longipalpiswas not detected. Our results are indicative of an ongoing transmission in the area.

  12. Visceral Leishmaniasis Eradication is a Reality: Data from a Community-based Active Surveillance in Bangladesh.

    Science.gov (United States)

    Ferdousi, Farhana; Alam, Mohammad S; Hossain, Mohammad S; Ma, Enbo; Itoh, Makoto; Mondal, Dinesh; Haque, Rashidul; Wagatsuma, Yukiko

    2012-12-01

    More than 20 million people in Bangladesh are considered at risk of developing visceral leishmaniasis (VL). A community-based active surveillance was conducted in eight randomly selected villages in a highly endemic area of Bangladesh from 2006 to 2008. A total of 6,761 individuals living in 1,550 mud-walled houses were included in the active surveillance. Rapid rK39 dipstick tests were conducted throughout the study period to facilitate the case diagnosis. Individuals with previous or current clinical leishmaniasis were identified on the basis of the case definition of the VL elimination program. Untreated cases of suspected VL were referred to the hospital for treatment. Socioeconomic and environmental information including bed net use was also collected. In 2006, the annual incidence of clinical leishmaniasis in the study area was 141.9 cases per 10,000 population, which was significantly increased by the following year owing to community-based active surveillance for case detection and reporting. However, early case detection and early referral for treatment led to a significant decrease in incidence in 2008. This study suggests that community-based active surveillance using a simple diagnostic tool might play a role in achieving the goal of the VL elimination program.

  13. Indian visceral leishmaniasis with extensive lymphadenopathy - An unusual presentation: A case report with literature review.

    Science.gov (United States)

    Agarwal, Poojan; Kumar, Vijay; Kaushal, Manju; Kumari, Manju; Chaudhary, Arvind

    2017-01-01

    Visceral leishmaniasis (VL), also known as kala-azar, is a life-threatening systemic disease caused by the obligate intracellular protozoan, Leishmania, and transmitted to humans by the female phlebotomine sand fly (Phlebotomus argentipes). The disease is fatal, if left untreated. We report a case of a patient clinically suspected of disseminated tuberculosis, but fine needle aspiration cytology of cervical and axillary lymph nodes yielded a diagnosis of leishmaniasis. Diagnosis of VL was challenging as the disease closely mimicked tuberculosis in the setting of extensive lymphadenopathy including conglomerate of mesenteric lymph nodes, on and off fever, and granulomatous lymphadenitis on aspiration. Bone marrow examination was further performed. A detailed workup revealed patient to be severely immunocompromised and newly diagnosed human immunodeficiency virus (HIV) positive. Worldwide, India has the largest number of VL cases, accounting for 40%-50% of world's disease burden and the second largest HIV-infected population, accounting for approximately 10% of the global disease burden. HIV increases the risk of developing VL by 100-2320 times in endemic areas and concurrently VL promotes the clinical progression of HIV disease. Co-infection with HIV alters the body's immune response to leishmaniasis thus leading to unusual presentations. This case highlights the diagnostic problem in the aforesaid setting. Moreover, co-infection with HIV in VL can be a potential source of drug resistance. An early diagnosis and intensified treatment is the key to patient management.

  14. Sero-epidemiological assessment and diagnosis of visceral leishmaniasis in an endemic locality using Fast Agglutination Screening Test (FAST)

    NARCIS (Netherlands)

    Hailu, A.; Kroon, C. C. M.; Schoone, G. J.; Berhe, N.; Schallig, H. D. F. H.; Kager, P. A.

    2002-01-01

    The Fast Agglutination Screening Test (FAST) was employed on sera obtained from an endemic area of visceral leishmaniasis in southwestern Ethiopia, in February 2000. The study involved (i) active case detection among 1575 residents of two villages; and (ii) passive case detection in an outpatient

  15. Leishmania chagasi/infantum: further investigations on Leishmania tropisms in atypical cutaneous and visceral leishmaniasis foci in Central America.

    NARCIS (Netherlands)

    Campos Ponce, M.; Ponce, C.; Ponce, E.; Maingon, R.D.

    2005-01-01

    In Central America, apparently genetically identical Leishmania chagasi/infantum parasites cause cutaneous (CL) and visceral leishmaniasis (VL), the latter being more frequent in young children. The present study investigated if there were pathology-related differences in virulence between Honduran

  16. Leishmania chagasi/infantum : further investigations on Leishmania tropisms in atypical cutaneous and visceral leishmaniasis foci in Central America

    NARCIS (Netherlands)

    Campos Ponce, M.; Ponce, C.; Ponce, E; Maingon, R.D.

    2005-01-01

    In Central America, apparently genetically identical Leishmania chagasi/infantum parasites cause cutaneous (CL) and visceral leishmaniasis (VL), the latter being more frequent in young children. The present study investigated if there were pathology-related differences in virulence between Honduran

  17. Molecular tools for diagnosis of visceral leishmaniasis: systematic review and meta-analysis of diagnostic test accuracy

    NARCIS (Netherlands)

    de Ruiter, C. M.; van der Veer, C.; Leeflang, M. M. G.; Deborggraeve, S.; Lucas, C.; Adams, E. R.

    2014-01-01

    Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that

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

    Science.gov (United States)

    Abass, Elfadil; Kang, Cholho; Martinkovic, Franjo; Semião-Santos, Saul J; Sundar, Shyam; Walden, Peter; Piarroux, Renaud; El Harith, Abdallah; Lohoff, Michael; Steinhoff, Ulrich

    2015-01-01

    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 (pLeishmania 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.

  19. Epidemiology and clinical manifestations of visceral and cutaneous leishmaniasis in Baringo District, Rift Valley, Kenya. A literature review

    NARCIS (Netherlands)

    Schaefer, K. U.; Kurtzhals, J. A.; Sherwood, J. A.; Githure, J. I.; Kager, P. A.; Muller, A. S.

    1994-01-01

    Visceral leishmaniasis (VL), caused by Leishmania donovani, is endemic in Baringo District, Kenya. The disease has a focal distribution in the dry, hot areas below 1500 metres. Infections may be characterized as follows: 1) asymptomatic, 2) subclinical and self-limiting (not medically identifiable),

  20. Comparison of serological assays for the diagnosis of canine visceral leishmaniasis in animals presenting different clinical manifestations

    NARCIS (Netherlands)

    Ferreira, Eduardo de Castro; de Lana, Marta; Carneiro, Mariangela; Reis, Alexandre Barbosa; Paes, Daniela Vieira; da Silva, Eduardo Sergio; Schallig, Henk; Ferreira Gontijo, Celia Maria

    2007-01-01

    Three serological methods, indirect fluorescent immunoassay (IFI), enzyme-linked immunosorbent assay (ELISA) and direct agglutination test (DAT) that are commonly employed in the diagnosis of canine visceral leishmaniasis (CVL), have been assessed. A total of 234 domestic dogs, drawn from an area in

  1. UDP-Gal: N-acetylglucosamine beta 1-4 galactosyltransferase expressing live attenuated parasites as vaccine for visceral leishmaniasis.

    Science.gov (United States)

    Bhaumik, Siddhartha Kumar; Singh, Manoj Kumar; Karmakar, Subir; De, Tripti

    2009-08-01

    As compared to cutaneous leishmaniasis, vaccination against visceral leishmaniasis (VL) has received limited attention. In this study, we demonstrate for the first time that an UDP-Galactose: N-acetylglucosamine beta 1-4 galactosyltransferase (GenBank Accession No. EF159943) expressing attenuated LD clonal population (A-LD) is able to confer protection against the experimental challenge with the virulent LD AG83 parasite. A-LD was also effective in established leishmania infection. The vaccinated animals showed both cell mediated (in vitro T-cell proliferation, and DTH response) and humoral responses (Th1 type). These results demonstrate the potential of the attenuated clones as an immunotherapeutic and immunoprophylactic agent against visceral leishmaniasis.

  2. Visceral leishmaniasis in the state of Sao Paulo, Brazil: spatial and space-time analysis.

    Science.gov (United States)

    Cardim, Marisa Furtado Mozini; Guirado, Marluci Monteiro; Dibo, Margareth Regina; Chiaravalloti, Francisco

    2016-08-11

    To perform both space and space-time evaluations of visceral leishmaniasis in humans in the state of Sao Paulo, Brazil. The population considered in the study comprised autochthonous cases of visceral leishmaniasis and deaths resulting from it in Sao Paulo, between 1999 and 2013. The analysis considered the western region of the state as its studied area. Thematic maps were created to show visceral leishmaniasis dissemination in humans in the municipality. Spatial analysis tools Kernel and Kernel ratio were used to respectively obtain the distribution of cases and deaths and the distribution of incidence and mortality. Scan statistics were used in order to identify spatial and space-time clusters of cases and deaths. The visceral leishmaniasis cases in humans, during the studied period, were observed to occur in the western portion of Sao Paulo, and their territorial extension mainly followed the eastbound course of the Marechal Rondon highway. The incidences were characterized as two sequences of concentric ellipses of decreasing intensities. The first and more intense one was found to have its epicenter in the municipality of Castilho (where the Marechal Rondon highway crosses the border of the state of Mato Grosso do Sul) and the second one in Bauru. Mortality was found to have a similar behavior to incidence. The spatial and space-time clusters of cases were observed to coincide with the two areas of highest incidence. Both the space-time clusters identified, even without coinciding in time, were started three years after the human cases were detected and had the same duration, that is, six years. The expansion of visceral leishmaniasis in Sao Paulo has been taking place in an eastbound direction, focusing on the role of highways, especially Marechal Rondon, in this process. The space-time analysis detected the disease occurred in cycles, in different spaces and time periods. These meetings, if considered, may contribute to the adoption of actions that aim to

  3. Mathematical modelling for Zoonotic Visceral Leishmaniasis dynamics: A new analysis considering updated parameters and notified human Brazilian data

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    Helio Junji Shimozako

    2017-05-01

    Full Text Available Brazil is one of the highest endemic countries for Zoonotic Visceral Leishmaniasis: according to the Brazilian Ministry of Health, the annual number of new human cases and deaths due to this disease has been increasing for the last 20 years. In addition, regarding the Americas, the specific relationship between canine and human for Visceral Leishmaniasis dynamics is still not well understood. In this work we propose a new model for Zoonotic Visceral Leishmaniasis, based on the models previously published by Burattini et al. (1998 and Ribas et al. (2013. Herein, we modeled the disease dynamics using a modified set of differential equations from those two authors, considering the same assumptions (inclusion of human, dog and sandfly populations, all constants over time. From this set of equations we were able to calculate the basic reproduction number R0 and to analyze the stability and sensitivity of the system to the parameters variability. As main result, when the stability of the system is reached, the normalized reporting human cases rate is estimated in 9.12E-08/day. This estimation is very close to the 2015 report from Araçatuba city, 5.69E-08/day. We also observed from stability and sensitivity analysis that the activity of sandfly population is critical to introduction and maintenance of Zoonotic Visceral Leishmaniasis in the population. In addition, the importance of dog as source of infection concentrates on latent dog, since it does not show clinical symptoms and signs and, therefore, has a great contribution to disease dissemination. As conclusion, considering the presently ethical issues regarding to elimination of positive dog in Brazil and the highly sensitivity of disease dynamics on sandfly population, we recommend that the sandfly population control should be prioritized. Keywords: Zoonotic Visceral Leishmaniasis, Disease dynamics, Mathematical modelling, Epidemiology

  4. Transmission potential, skin inflammatory response, and parasitism of symptomatic and asymptomatic dogs with visceral leishmaniasis

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    Goto H

    2008-11-01

    Full Text Available Abstract Background Visceral leishmaniasis in Brazil is caused by the protozoan Leishmania (Leishmania chagasi and it is transmitted by sandfly of the genus Lutzomyia. Dogs are an important domestic reservoir, and control of the transmission of visceral leishmaniasis (VL to humans includes the elimination of infected dogs. However, though dogs are considered to be an important element in the transmission cycle of Leishmania, the identification of infected dogs representing an immediate risk for transmission has not been properly evaluated. Since it is not possible to treat infected dogs, they are sacrificed when a diagnosis of VL is established, a measure that is difficult to accomplish in highly endemic areas. In such areas, parameters that allow for easy identification of reservoirs that represents an immediate risk for transmission is of great importance for the control of VL transmission. In this study we aimed to identify clinical parameters, reinforced by pathological parameters that characterize dogs with potential to transmit the parasite to the vector. Results The major clinical manifestations of visceral leishmaniasis in dogs from an endemic area were onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. The transmission potential of these dogs was assessed by xenodiagnosis using Lutzomyia longipalpis. Six of nine symptomatic dogs were infective to Lutzomyia longipalpis while none of the five asymptomatic dogs were infective to the sandfly. Leishmania amastigotes were present in the skin of all clinically symptomatic dogs, but absent in asymptomatic dogs. Higher parasite loads were observed in the ear and ungueal region, and lower in abdomen. The inflammatory infiltrate was more intense in the ears and ungueal regions of both symptomatic and asymptomatic dogs. In clinically affected dogs in which few or none Leishmania amastigotes were observed, the inflammatory infiltrate was constituted mainly of lymphocytes

  5. 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

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    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)

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

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    Carrillo, Eugenia; Jimenez, Maria Angeles; Sanchez, Carmen; Cunha, Joana; Martins, Camila Marinelli; da Paixão Sevá, Anaiá; Moreno, Javier

    2014-01-01

    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.

  7. 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.

  8. PARTICIPATION OF TICKS IN THE INFECTIOUS CYCLE OF CANINE VISCERAL LEISHMANIASIS, IN TERESINA, PIAUÍ, BRAZIL

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    José Henrique Furtado Campos

    2014-07-01

    Full Text Available In this study, we detected Leishmania spp. infection in R. sanguineus collected from dogs that were naturally infected with L. (L. infantum. We examined 35 dogs of both sexes and unknown ages. The infected dogs were serologically positive by the immunofluorescence antibody test (IFAT, enzyme-linked immunosorbent assay (ELISA, and Quick Test-DPP (Dual Path Platform, as well as parasitological examination of a positive skin biopsy or sternal bone marrow aspiration. Ten negative dogs were included as controls. The ticks that infested these dogs were collected in pools of 10 adult females per animal. The PCR was performed with specific primers for Leishmania spp., which amplified a 720-bp fragment. Of the 35 analyzed samples, a product was observed in eight samples (8/35; 22.9%. We conclude that the presence of parasite DNA suggests that ticks participate in the zoonotic cycle of canine visceral leishmaniasis, in the city of Teresina, Piauí.

  9. Immunotherapy and targeted therapies in treatment of visceral leishmaniasis: current status and future prospects.

    Science.gov (United States)

    Singh, Om Prakash; Sundar, Shyam

    2014-01-01

    Visceral leishmaniasis (VL) is a vector-borne chronic infectious disease caused by the protozoan parasite Leishmania donovani or Leishmania infantum. VL is a serious public health problem, causing high morbidity and mortality in the developing world with an estimated 0.2-0.4 million new cases each year. In the absence of a vaccine, chemotherapy remains the favored option for disease control, but is limited by a narrow therapeutic index, significant toxicities, and frequently acquired resistance. Improved understanding of VL pathogenesis offers the development and deployment of immune based treatment options either alone or in combination with chemotherapy. Modulations of host immune response include the inhibition of molecular pathways that are crucial for parasite growth and maintenance; and stimulation of host effectors immune responses that restore the impaired effector functions. In this review, we highlight the challenges in treatment of VL with a particular emphasis on immunotherapy and targeted therapies to improve clinical outcomes.

  10. Immunotherapy and Targeted Therapies in Treatment of Visceral Leishmaniasis: current status and future prospects

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    Om Prakash eSingh

    2014-06-01

    Full Text Available Visceral leishmaniasis (VL is a vector-borne chronic infectious disease caused by the protozoan parasite Leishmania donovani or Leishmania infantum. VL is a serious public health problem, causing high morbidity and mortality in the developing world with an estimated 0.2 -0.4 million new cases each year. In the absence of a vaccine, chemotherapy remains the favoured option for disease control, but is limited by a narrow therapeutic index, significant toxicities, and frequently acquired resistance. Improved understanding of VL pathogenesis offers the development of immune based treatment options either alone or in combination with chemotherapy. Modulations of host immune responses include the approaches that inhibit molecular pathways, crucial for parasite growth and maintenance; and stimulate host effectors immune responses that restore the impaired effector functions. In this review, we highlight the challenges in treatment of VL with a particular emphasis on immunotherapy and targeted therapies to improve clinical outcomes.

  11. Leishmania infantum: lack of parasite resistance to amphotericin B in a clinically resistant visceral leishmaniasis.

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    Durand, R; Paul, M; Pratlong, F; Rivollet, D; Dubreuil-Lemaire, M L; Houin, R; Astier, A; Deniau, M

    1998-08-01

    Amphotericin B (AmB) has been used as a second-line treatment of visceral leishmaniasis, particularly in human immunodeficiency virus-positive patients. AmB median effective doses (ED50s) were determined on an isolate obtained before any treatment and on a second isolate obtained 4 years later from the same AmB-treated patient. ED50s were similar (0.059 and 0.067 mg/kg of body weight, respectively), demonstrating the first evidence of AmB ED50 stability of Leishmania infantum after a long-term drug exposure. An isoenzymatic study was performed in order to verify that the second isolate originated from the same parasite as the first isolate. The present case report showed that treatment failure was not due to parasite resistance in spite of a prolonged exposure to the drug.

  12. Molecular diagnosis of canine visceral leishmaniasis through the technique of probe gold nanoparticles (AuNPprobes

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    Janaina Marcela Assunção Rosa

    2014-02-01

    Full Text Available The aim of this study was to comparatively evaluate the diagnostic methods of Canine Visceral Leishmaniasis (CVL, using the indirect immunofluorescence assay (IFA, the probe Gold Nanoparticles (AuNPprobes and PCR in liver samples. We analyzed 25 samples of animals positive by IFA and 10 samples from animals negative to PCR. The probe AUNP used was based on specific sequence for Leishmania infantum kDNA. The results showed that when compared to the IFA sorology the AuNPprobe showed a sensitivity and specificity of 56% and 80%, respectively. When compared to PCR method, the AuNPprobe had a sensitivity of 68% and specificity of 81%. The AuNPprobe can be an alternative to traditional diagnostic methods (PCR and IFA due to its ease of implementation, immediate result, low cost and little need for laboratory infrastructure.

  13. Ocular diseases in dogs naturally affected by visceral leishmaniasis in Teresina, Piauí, Brazil

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    Marcus Valérius de Matos Freitas

    2017-09-01

    Full Text Available ABSTRACT: This study aimed to characterize ocular diseases in dogs naturally affected by visceral leishmaniasis in Teresina, Piauí State, Brazil. The diagnosis was made using parasitological exams of the bone-marrow and lymph-node samples. The main ophthalmological findings were uveitis, conjunctivitis, blepharitis, keratitis, and keratoconjunctivitis sicca. Normocytic normochromic anemia was the main hematological finding, followed by thrombocytopenia. Plasma proteins were also considered, and hyperproteinemia, hypergammaglobulinemia, and hypoalbuminemia were observed. Ocular histopathological examination revealed mild inflammation involving lymphocytes, monocytes, and macrophages. Results indicate the need to perform a differential diagnosis to rule out or establish the presence of Leishmania sp. in dogs presenting with ophthalmic lesions in endemic regions.

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

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    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. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Rearing and Colonization of Lutzomyia evansi (Diptera: Psychodidae, a Vector of Visceral Leishmaniasis in Colombia

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    Montoya-Lerma James

    1998-01-01

    Full Text Available The sandfly Lutzomyia evansi from a focus of visceral leishmaniasis in northern Colombia was reared and maintained under laboratory conditions for five generations. The average time for total development was 41.8 days (range = 35.1- 49.6 at 25 oC and 89-95% of relative humidity. The mean number of eggs laid was lower in laboratory bred females either in pots (13.2 eggs/female or vials (29.9 eggs/female than in wild caught females (33.4 eggs/female. Immature mortality, mainly due to fungal and mite contamination, was higher during the first two instars than in the remaining immature stages. Adults were robust and healthy although difficult to feed on hamster or chick skin membrane. In summary, Lu. evansi is a colonizable species but requires specific conditions.

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

    National Research Council Canada - National Science Library

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

    2013-01-01

    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...

  17. Serological diagnosis of canine visceral leishmaniasis in Brazil: systematic review and meta-analysis.

    Science.gov (United States)

    Peixoto, Henry Maia; de Oliveira, Maria Regina Fernandes; Romero, Gustavo Adolfo Sierra

    2015-03-01

    To evaluate the quality and accuracy of serological diagnosis of canine visceral leishmaniasis in the Americas. A systematic review found original studies in the databases MEDLINE, EMBASE and LILACS up to November 2012 and in complementary sources up to February 2013. Studies were evaluated in accordance with QUADAS 2 and STARD parameters and recommended in accordance with GRADE parameters. Meta-analysis was carried out with Meta-DiSc software, using the random-effect model. Two hundred and eighty-four studies were identified, of which 25 met the inclusion criteria, comprising the final synthesis. All but one was conducted in Brazil, and only two were judged to be of good quality. 15 studies involving immuno-enzymatic tests with crude antigens (cELISA), 11 studies on indirect immunofluorescence tests (IFAT) and three on the immunochromatographic dual-path platform (DPP) test were meta-analysed. The combined results for sensitivity and specificity were cELISA: 0.89 (CI 95% 0.87-0.91) and 0.87 (CI 95% 0.86-0.88); IFAT: 0.88 (CI 95% 0.85-0.91) and 0.63 (CI 95% 0.61-0.65); and DPP: 0.83 (CI 95% 0.78-0.88) and 0.73 (CI 95% 0.70-0.75). Enzyme-linked immunosorbent assay with crude antigens and DPP tests have moderate accuracy for the diagnosis of canine visceral leishmaniasis, and the quality of the design, implementation and analysis of validation studies on diagnostic tests for this disease urgently require improvement. The recommendation for use of the evaluated tests is based on evidence that is scarce and restricted to Brazil. © 2014 John Wiley & Sons Ltd.

  18. T lymphocyte immunophenotypes in the cerebrospinal fluid of dogs with visceral leishmaniasis.

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    Grano, Fernanda G; Silva, José Eduardo Dos S; Melo, Guilherme D; Perosso, Juliana; Lima, Valéria M F; Machado, Gisele F

    2016-12-15

    Visceral leishmaniasis (VL) is a disease causing several clinical manifestations in dogs, including neurological disorders. Nevertheless, there are few studies related to the evaluation of the brain alterations during VL. Evidences of the involvement of cerebral barriers in infected dogs was reported, including the presence of brain inflammatory infiltrate, with a predominance of CD3+ T cells. Therefore, the aim of this study was to determine the immunophenotypes of T lymphocytes in the cerebrospinal fluid (CSF), as well as in peripheral blood, and to correlate with brain alterations in dogs with VL. We detected elevated percentages of double negative (DN) and double positive (DP) T cells in the CSF, with a predominance of TCRαb. In the histopathological analysis, we observed a predominance of lymphoplasmacytic infiltrate, mainly in leptomeninges, ranging from mild to intense, and we observed a positive correlation between the intensity of inflammation in the subependymal area and the DN T cells of the CSF. Thus, the DN T cells seem be acting as villains of the immune system through pro-inflammatory mechanisms. Further, the proportion of the different population of CSF T cells did not differ from those observed in the blood, which provides us with more evidence of blood-CSF barrier breakdown. Together, the results provide more explanation to the inflammation observed in the brain of dogs with VL, which the DN T cells contribute to the origin and progression of the neurological disease. This study provides insight into the immunophenotypes of T lymphocytes in the CSF during canine visceral leishmaniasis. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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    Belo, Vinícius Silva; Werneck, Guilherme Loureiro; Barbosa, David Soeiro; Simões, Taynãna César; Nascimento, Bruno Warlley Leandro; da Silva, Eduardo Sérgio; Struchiner, Claudio José

    2013-01-01

    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. 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. 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 for which knowledge is poor.

  20. 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

  1. Situational Analysis of Visceral Leishmaniasis in the Most Important Endemic Area of the Disease in Iran

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    Eslam Moradi-Asl

    2017-12-01

    Full Text Available Background: Visceral leishmaniasis is one of the most important vector borne diseases in the world, transmitted by sand flies. Despite efforts to prevent the spread of the disease, cases continue worldwide. In Iran, the disease usually occurs in children under 10 years.  In the absence of timely diagnosis and treatment, the mortality rate is 95–100%. The main objective of this study was to determine the spatial and temporal distribution of visceral leishmaniasis as well as its correlation with climatic factors for determining high-risk areas in an endemic focus in northwestern Iran.Methods: In this cross-sectional study, data on VL cases were collected from local health centers in Ardabil Prov­ince, Iran during 2001–2015 to establish a geodatabase using ArcGIS10.3. Data analysis was conducted using SPSS23 and ArcMap Spatial Analyst. MaxEnt model was used to determine ecologically suitable nichesfor the disease.Results: Two hotspots were found in Meshkinshahr and Germi counties with 59% and 23% of total cases, respec­tively. There was an increase in the incidence rate of VL in Ardabil County from 2.9 in 2009 to 9.2/100,000 population in 2015. There was no spa­tial autocorrelation between county and total number of cases (P> 0.05. Higher NDVI, lower altitude and southern as­pects had positive effects on the presence probability of VL.Conclusion: The number of cases of this disease have been rising since 2013 and doubled in 2015. According to the derived distribution maps, the disease is spreading to new locations such as Ardabil and Namin counties.

  2. Prophylactic potential of autoclaved Leishmania donovani with BCG against experimental visceral leishmaniasis.

    Science.gov (United States)

    Srivastava, J K; Misra, A; Sharma, P; Srivastava, B; Naik, S; Dube, A

    2003-08-01

    The prophylactic efficacy of autoclaved Leishmania donovani (ALD) and autoclaved L. major (ALM)--a heterologous vaccine developed against cutaneous leishmaniasis (used as a reference vaccine), along with BCG--was evaluated against L. donovani in hamsters (Mesocricetus auratus). Animals were immunized with triple doses (21 days apart) of either ALD or ALM (1.0 mg) with or without BCG (0.1 mg) and challenged 21 days later with 1 x 10(6) L. donovani amastigotes intracardially. Animals immunized with ALM + BCG and ALD + BCG yielded 94.3% and 86.1% parasite inhibition respectively in comparison to the BCG only and unvaccinated controls. Fifty and 33.3% of the vaccinated animals (ALM + BCG and ALD + BCG respectively) were completely devoid of parasites when tested on day 45 post-challenge (p.c.) and survived till the experiment was terminated. The mean survival of ALM + BCG and ALD + BCG groups (animals harbouring parasites) was longest (168 and 139 days respectively). No significant increase in anti-leishmanial antibody level (ELISA) was noticed in ALD + BCG and ALM + BCG groups whereas it increased progressively in the rest of the experimental groups. The lymphoproliferative responses to PHA and Con A, of the 2 vaccinated groups were comparable to that of normal controls on day 45 p.c. The study suggests that ALD along with BCG can offer substantial protection against visceral leishmaniasis in hamsters.

  3. 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. © M.E.C. Dorval et al., published by EDP Sciences, 2016.

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

    Science.gov (United States)

    Farahmand, Mahin; Nahrevanian, Hossein

    2016-07-01

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

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

    Science.gov (United States)

    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

  6. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Canine visceral leishmaniasis in urban and rural areas of Northeast Brazil.

    Science.gov (United States)

    Queiroz, Paula V S; Monteiro, Glória R G; Macedo, Virgínia P S; Rocha, Maria A C; Batista, Leopoldina M M; Queiroz, José W; Jerônimo, Selma M B; Ximenes, Maria F F M

    2009-04-01

    The purpose of this study was to determine the clinical and laboratory profiles of canine leishmaniasis in two distinct areas. Dogs from urban and rural areas were examined. The population studied in the metropolitan area included 54 dogs. Of these, 20 (37%) animals did not present with any signs suggestive of visceral leishmaniasis (VL). Among these, only eight were confirmed negative by ELISA (rK39 and CE) and 12 dogs, clinically negative for leishmaniasis, were seropositive by ELISA (rK39 and CE). Thinness, conjunctivitis and onychogryphosis were the most frequent clinical signs in the urban areas, followed by crusty lesions, alopecia, ulcerated lesions, hyperkeratosis and exfoliation. In the metropolitan area human VL cases occurred mainly in 1991, 1992, 1999 and 2000. In the rural areas the ELISA rK39 test detected a seroprevalence of 11.3% and ELISA CE (Leishmania crude extract) of 20.6%. Thirty-nine dogs were examined 6 months after the first visit. Serological exams using rK39 antigen showed seroconversion of only one dog, whereas Leishmania CE showed seroconversion of 13 (33.4%) dogs. In this rural environment 83.3% of the positive dogs were asymptomatic. Lutzomyia intermedia and Lu. longipalpis were the most predominant sandfly vector species. Amastigotes were identified in spleen and liver fragments of symptomatic necropsied animals. PCR amplification of DNA isolated from promastigote culture indicated that the species was Leishmania chagasi. This finding suggests that delayed diagnosis and euthanasia of potentially infectious animals may occur with an increased transmission risk to sandflies and subsequently to humans.

  8. 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.

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

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    Hossein Mortazavi

    2015-06-01

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

  10. 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

  11. The Burden of Visceral Leishmaniasis in India: Challenges in Using Remote Sensing and GIS to Understand and Control

    OpenAIRE

    Bhunia, Gouri Sankar; Kesari, Shreekant; Chatterjee, Nandini; Kumar, Vijay; Das, Pradeep

    2013-01-01

    Visceral leishmaniasis (VL) continues to constitute immense public health problems and be an obstacle to socioeconomic development in India. The scrutiny of this disease remains a necessary step in its control, eradication, and prevention. Space technologies proffer new opportunities for rapid appraisal of endemic areas, stipulation of trustworthy estimation of populations at risk, prediction of disease distributions in areas that lack baseline data and are difficult to access, and guiding in...

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

    OpenAIRE

    Mohebali, Mehdi; Arzamani, Kourosh; Zarei, Zabiholah; Akhoundi, Behnaz; Hajjaran, Homa; Raeghi, Saber; Heidari, Zahra; Motavalli-Haghi, Seyed Mousa; Elikaee, Samira; Mousazadeh-Mojarrad, Ahmad; Kakoei, Zahra

    2016-01-01

    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 serol...

  13. The Cytotoxic T Lymphocyte Antigen-4 +49A/G Single Nucleotide Polymorphism Association With Visceral Leishmaniasis

    OpenAIRE

    Hajilooi, Mehrdad; Lotfi, Pegah; Seif, Farhad; Bazmani, Ahad; Momeni, Mohammad; Ravary, Ali; Kazemi Arababadi, Mohammad; Khalilian, Ali Reza

    2014-01-01

    Background: Several lines of evidence approve that innate and adaptive immunity play key roles in the defense against visceral leishmaniasis (VL). The polymorphism within the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene alters its expression. Objectives: The main aim of this study was to evaluate the polymorphism within the +49 position of the CTLA-4 gene of Iranian patients with VL in comparison with healthy controls. Materials and Methods: In this cross-sectional study, 88 patients with c...

  14. 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.

  15. Introduction and expansion of human American visceral leishmaniasis in the state of Sao Paulo, Brazil, 1999-2011.

    Science.gov (United States)

    Cardim, Marisa Furtado Mozini; Rodas, Lilian A Colebrusco; Dibo, Margareth Regina; Guirado, Marluci Monteiro; Oliveira, Agda Maria; Chiaravalloti-Neto, Francisco

    2013-08-01

    To analyze the spread of human American visceral leishmaniasis and identify the key municipalities for developing surveillance and control activities. The area of the study was composed of the 316 municipalities in the state of Sao Paulo belonging to the five health districts in which human American visceral leishmaniasis occurs, using data on autochthonous cases and deaths according to the reporting year and municipality in which the death occurred. The incidence, mortality and case fatality rates for each municipality and for the entire area were calculated. An empirical Bayes estimator was used to calculate the local Bayesian incidence and rates of mortality per municipality, and Kriging was used to visualize the spatial distribution of temperature and rainfall. A total of 73 municipalities with transmission of the disease were identified. Human American visceral leishmaniasis was first detected in areas with higher temperatures and lower rainfall, but it also spread in cooler and wetter areas. The expansion of human American visceral leishmaniasis occurred along a main axis of dissemination, from Northwest to Southeast, following the Marechal Rondon highway and the Bolivia-Brazil gas pipeline, and along a secondary axis that was derived from the main axis, which runs both North and South, following the highway network. Rates of incidence according to health district exhibit a peak, followed by a fall, except the Sao Jose do Rio Preto region. Higher concentrations of municipalities with high incidence and mortality rates were observed in the Araçatuba, Presidente Prudente and Marília health districts. This study indicates possible determinants of the spread of disease, including the Marechal Rondon highway and the construction of the Bolivia-Brazil gas pipeline. Climatic factors seemed to play no role in the spread. The use of spatial analysis techniques allowed the municipalities where cases and deaths are possibly underreported to be identified, which

  16. Unusual presentation of mucocutaneous leishmaniasis in HIV-infected patient.

    Science.gov (United States)

    Bains, Anupama; Vedant, Deepak; Gupta, Priyanka; Tegta, G R

    2016-01-01

    Leishmaniasis is caused by protozoan parasite of genus leishmania. Visceral leishmaniasis, diffuse cutaneous leishmaniasis, and atypical forms of cutaneous leishmaniasis are common in HIV-infected patients. Our patient presented with an obstructive mass in nasal cavity and was diagnosed as a case of mucocutaneous leishmaniasis. Spontaneous healing of lesions in HIV-infected patients is rare rather they are unresponsive to treatment and have frequent relapses, especially in patients with low CD4 count. However, in our patient, the lesion improved significantly after 2 months of highly active antiretroviral therapy and co-trimoxazole prophylaxis.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis.

    Science.gov (United States)

    Cecílio, Pedro; Pérez-Cabezas, Begoña; Fernández, Laura; Moreno, Javier; Carrillo, Eugenia; Requena, José M; Fichera, Epifanio; Reed, Steven G; Coler, Rhea N; Kamhawi, Shaden; Oliveira, Fabiano; Valenzuela, Jesus G; Gradoni, Luigi; Glueck, Reinhard; Gupta, Gaurav; Cordeiro-da-Silva, Anabela

    2017-11-01

    The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the "natural infection".

  19. Clinical severity of visceral leishmaniasis is associated with changes in immunoglobulin g fc N-glycosylation.

    Science.gov (United States)

    Gardinassi, Luiz Gustavo; Dotz, Viktoria; Hipgrave Ederveen, Agnes; de Almeida, Roque Pacheco; Nery Costa, Carlos Henrique; Costa, Dorcas Lamounier; de Jesus, Amélia Ribeiro; Mayboroda, Oleg A; Garcia, Gustavo Rocha; Wuhrer, Manfred; de Miranda Santos, Isabel Kinney Ferreira

    2014-12-02

    Visceral leishmaniasis (VL) has a high fatality rate if not treated; nevertheless, the majority of human infections with the causative agent, Leishmania infantum chagasi, are asymptomatic. Although VL patients often present with increased levels of serum immunoglobulins, the contribution of antibodies to resistance or progression to disease remains unknown. Effector and regulatory functions of antibodies rely on their interactions with type I and II Fc receptors, and these interactions are tuned by the patterns of antibody Fc N-glycosylation. In view of these facts, we applied a robust method of IgG Fc N-glycopeptide profiling of serum samples from 187 patients with VL, 177 asymptomatic individuals, 116 endemic controls (individuals residing in areas where VL is endemic) and 43 nonendemic controls (individuals living in an area where VL is not endemic). We show that, in comparison to the overall IgG Fc N-glycan profiles of asymptomatic or uninfected healthy individuals, those of patients with VL are profoundly altered. These changes correlate with levels of serum cytokines and the inflammation marker C-reactive protein. We also fitted univariate and multivariate ordinal logistic regression models to demonstrate the ability of IgG Fc N-glycosylation features and immunity regulators present in serum to predict disease severity in VL patients. Importantly, we show that Fc N-glycosylation profiles change after treatment of VL. This study introduces important concepts contributing to the understanding of antibody responses in infections with Leishmania parasites and provides new insights into the pathology of human VL. Immunoglobulins (Ig) have been shown to present pro- and anti-inflammatory functions according to the profile of carbohydrates attached to their Fc region. Glycosylation features of serum IgG have been examined in relation to several autoimmune and infectious diseases and provide a mechanistic basis for the protective or pathogenic role of antibodies

  20. Epidemiology of visceral leishmaniasis among children in Gadarif hospital, eastern Sudan

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    Mohammed Ahmed A. Ahmed

    2016-12-01

    Full Text Available Abstract Background Since 1900s, visceral leishmaniasis (VL has been among the most important health problems in Sudan, particularly in the endemic areas such as eastern and central regions. Methods This was a cross sectional, hospital-based study conducted from 1st January 2015 to 31st December 2015 to investigate the epidemiological factors of VL in Gadarif hospital, eastern Sudan. Results During the study period there were 47 identified children with VL among 145 suspected cases. The most common clinical presentations were fever (47, 100%, pallor (47, 100%, weight loss (40, 85.1%, splenomegaly (37, 78.7%, lymphadenopathy (33, 70.2%, vomiting (32, 68% cough (28, 59%, loss of appetite (22, 46.8%, diarrhoea (17, 36.1% and jaundice (5, 10.6%. With regard to the outcome after short term follow up 37 patients (78.8% improved without complications, while 3 (6.4%, 2 (4.3%, 2 (4.3%, 1 (2.1%, 1 (2.1% and 1 (2.1% developed pneumonia, otitis media, septicaemia, urinary tract infection, parasitic infestation and PKDL respectively. Lower mean of haemoglobin level was observed among the VL cases in comparison with the suspected cases (in whom VL was excluded haemoglobin level {8.9 (3.1 Vs 11 (6.3, P = 0.021}. Again more proportion of anaemic (47 (100% Vs 14 (14.2%, P = 0.000 and severely anaemic (23 (48.9% Vs 2 (2%, P = 0.006 patients was detected among the infected children. Using logistic regression analyses there was significant association between rural residence (CI = 1.5–24, OR = 19.1, P = 0.023, male gender (CI = 6.6–18.7, OR = 6.4, P = 0.001 and VL among children. Conclusions While there is an advance in prevention and management of visceral leishmaniasis our results indicate that VL is still a public health problem with its severe complications among children in eastern Sudan.

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

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    Meenakshi Sharma

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

  2. Parasite susceptibility to amphotericin B in failures of treatment for visceral leishmaniasis in patients coinfected with HIV type 1 and Leishmania infantum.

    Science.gov (United States)

    Lachaud, Laurence; Bourgeois, Nathalie; Plourde, Marie; Leprohon, Philippe; Bastien, Patrick; Ouellette, Marc

    2009-01-15

    Visceral leishmaniasis (VL) is an opportunistic infection that can occur among patients infected with human immunodeficiency virus type 1 (HIV-1) in areas where both infections are endemic. Highly active antiretroviral therapy has decreased the incidence of VL in southern Europe among HIV-1-infected patients, but VL is still observed among patients with low CD4 cell counts, and most coinfected patients receiving highly active antiretroviral therapy experienced relapse, despite initial treatment with liposomal amphotericin B. Through long-term monitoring of VL in 10 patients with HIV-1 infection and/or AIDS, we compared parasite strains derived from primary and secondary episodes of VL. All the patients have received many courses of amphotericin B treatment and/or prophylaxis. Through molecular techniques, we have shown that secondary episodes of VL can be attributable to relapse (7 of 10 episodes) or reinfection (3 of 10). We developed an assay to measure amphotericin B susceptibility and found no evidence of decreased susceptibility among strains isolated from patients, some of whom were infected with the same isolate for up to 10 years. This apparent absence of resistance, as determined by in vitro susceptibility testing, has important consequences and suggests that amphotericin B will remain a useful drug of choice against VL, even after repetitive treatments or prophylactic use.

  3. Discovery of novel vaccine candidates and drug targets against visceral leishmaniasis using proteomics and transcriptomics.

    Science.gov (United States)

    Kumari, Shraddha; Kumar, Awanish; Samant, Mukesh; Singh, Neeloo; Dube, Anuradha

    2008-11-01

    Among the three clinical forms (cutaneous, mucosal and visceral) of leishmaniasis visceral (VL) one is the most devastating type caused by the invasion of the reticuloendothelial system of human by Leishmania donovani, L. infantum and L. chagasi. India and Sudan account for about half the world's burden of VL. Current control strategy is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective due to the emergence of drug resistance. An understanding of resistance mechanism(s) operating in clinical isolates might provide additional leads for the development of new drugs. Further, due to the lack of fully effective treatment the search for novel immune targets is also needed. So far, no vaccine exists for VL despite indications of naturally developing immunity. Therefore, an urgent need for new and effective leishmanicidal agents and for this identification of novel drug and vaccine targets is imperative. The availability of the complete genome sequence of Leishmania has revolutionised many areas of leishmanial research and facilitated functional genomic studies as well as provided a wide range of novel targets for drug designing. Most notably, proteomics and transcriptomics have become important tools in gaining increased understanding of the biology of Leishmania to be explored on a global scale, thus accelerating the pace of discovery of vaccine/drug targets. In addition, these approaches provide the information regarding genes and proteins that are expressed and under which conditions. This review provides a comprehensive view about those proteins/genes identified using proteomics and transcriptomic tools for the development of vaccine/drug against VL.

  4. Isolated mucosal Leishmaniasis

    OpenAIRE

    Deepak Sundriyal; Naveen Kumar; Raj Kumar; Brijesh Sharma

    2013-01-01

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

  5. Efficacy of Leishmania donovani ribosomal P1 gene as DNA vaccine in experimental visceral leishmaniasis.

    Science.gov (United States)

    Masih, Shet; Arora, Sunil K; Vasishta, Rakesh K

    2011-09-01

    The acidic ribosomal proteins of the protozoan parasites have been described as prominent antigens during human disease. We present here data showing the molecular cloning and protective efficacy of P1 gene of Leishmania donovani as DNA vaccine. The PCR amplified complete ORF cloned in either pQE or pVAX vector was used either as peptide or DNA vaccine against experimentally induced visceral leishmaniasis in hamsters. The recombinant protein rLdP1 was given along with Freund's adjuvant and the plasmid DNA vaccine, pVAX-P1 was used alone either as single dose or double dose (prime and boost) in different groups of hamsters which were subsequently challenged with a virulent dose of 1×10(7) L. donovani (MHOM/IN/DD8/1968 strain) promastigotes by intra-cardiac route. While the recombinant protein rLdP1 or DNA vaccine pVAX-P1 in single dose format were not found to be protective, DNA vaccine in a prime-boost mode was able to induce protection with reduced mortality, a significant (75.68%) decrease in splenic parasite burden and increased expression of Th1 type cytokines in immunized hamsters. Histopathology of livers and spleens from these animals showed formation of mature granulomas with compact arrangement of lymphocytes and histiocytes, indicating its protective potential as vaccine candidate. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Radio-attenuated leishmanial parasites as immunoprophylactic agent against experimental murine visceral leishmaniasis.

    Science.gov (United States)

    Datta, Sanchita; Adak, Rupchand; Chakraborty, Priyanka; Haldar, Arun Kumar; Bhattacharjee, Surajit; Chakraborty, Anindita; Roy, Syamal; Manna, Madhumita

    2012-01-01

    The present study intends to evaluate the role of radio-attenuated leishmania parasites as immunoprophylactic agents for experimental murine visceral leishmaniasis. BALB/c mice were immunized with gamma (γ)-irradiated Leishmania donovani. A second immunization was given after 15 days of first immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes. Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the measurement of nitrite and superoxide anion generation by isolation of splenocytes and also by T-lymphocyte helper 1(Th1) and T-lymphocyte helper 2(Th2) cytokines release from the experimental groups. It was observed that BALB/c mice having prior immunization with radio-attenuated parasites showed protection against L. donovani infection through higher expression of Th1 cytokines and suppression of Th2 cytokines along with the generation of protective free radicals. The group of mice without prior priming with radio-attenuated parasites surrendered to the disease. Thus it can be concluded that radio-attenuated L. donovani may be used for. Copyright © 2011 Elsevier Inc. All rights reserved.

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

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

    2016-05-27

    Infection with Leishmania parasites results in a range of clinical manifestations and outcomes, the most severe of which is visceral leishmaniasis (VL). Vaccination will likely provide the most effective long-term control strategy, as the large number of vectors and potential infectious reservoirs renders sustained interruption of Leishmania parasite transmission extremely difficult. Selection of the best vaccine is complicated because, although several vaccine antigen candidates have been proposed, they have emerged following production in different platforms. To consolidate the information that has been generated into a single vaccine platform, we expressed seven candidates as recombinant proteins in E. coli. After verifying that each recombinant protein could be recognized by VL patients, we evaluated their protective efficacy against experimental L. donovani infection of mice. Administration in formulation with the Th1-potentiating adjuvant GLA-SE indicated that each antigen could elicit antigen-specific Th1 responses that were protective. Considering the ability to reduce parasite burden along with additional factors such as sequence identity across Leishmania species, we then generated a chimeric fusion protein comprising a combination of the 8E, p21 and SMT proteins. This E. coli -expressed fusion protein was also demonstrated to protect against L. donovani infection. These data indicate a novel recombinant vaccine antigen with the potential for use in VL control programs. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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

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

    2009-01-01

    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 delta-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-gamma, 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.

  9. Knockdown resistance mutations predict DDT resistance and pyrethroid tolerance in the visceral leishmaniasis vector Phlebotomus argentipes.

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    Gomes, Bruno; Purkait, Bidyut; Deb, Rinki Michelle; Rama, Aarti; Singh, Rudra Pratap; Foster, Geraldine Marie; Coleman, Michael; Kumar, Vijay; Paine, Mark; Das, Pradeep; Weetman, David

    2017-04-01

    Indoor residual spraying (IRS) with DDT has been the primary strategy for control of the visceral leishmaniasis (VL) vector Phlebotomus argentipes in India but efficacy may be compromised by resistance. Synthetic pyrethroids are now being introduced for IRS, but with a shared target site, the para voltage-gated sodium channel (VGSC), mutations affecting both insecticide classes could provide cross-resistance and represent a threat to sustainable IRS-based disease control. A region of the Vgsc gene was sequenced in P. argentipes from the VL hotspot of Bihar, India. Two knockdown resistance (kdr) mutations were detected at codon 1014 (L1014F and L1014S), each common in mosquitoes, but previously unknown in phlebotomines. Both kdr mutations appear largely recessive, but as homozygotes (especially 1014F/F) or as 1014F/S heterozygotes exert a strong effect on DDT resistance, and significantly predict survivorship to class II pyrethroids in short-duration bioassays. The mutations are present at high frequency in wild P. argentipes populations from Bihar, with 1014F significantly more common in higher VL areas. The Vgsc mutations detected appear to be a primary mechanism underlying DDT resistance in P. argentipes and a contributory factor in reduced pyrethroid susceptibility, suggesting a potential impact if P. argentipes are subjected to suboptimal levels of pyrethroid exposure, or additional resistance mechanisms evolve. The assays to detect kdr frequency changes provide a sensitive, high-throughput monitoring tool to detecting spatial and temporal variation in resistance in P. argentipes.

  10. Polymorphisms in tumor necrosis factor genes and susceptibility to visceral leishmaniasis in Moroccan children

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    Rajaa Ejghal

    2015-05-01

    Full Text Available Objective: To examine whether polymorphic alleles at these two loci are involved in the susceptibility to visceral leishmaniasis (VL in Moroccan children. Methods: We have genotyped polymorphisms by PCR-restricted fragment length polymorphisms in 102 patients with VL, 92 asymptomatic carriers [positive skin test delayedtype hypersensitivity (DTH+] and 40 healthy controls (negative skin test delayed-type hypersensitivity, with no history of Leishmania infection. Results: Regression analysis showed no significant association between polymorphisms of tumor necrosis factors-ααwhen comparing VL and DTH + group (P > 0.05. The associations were detected between VL and negative skin test delayed-type hypersensitivity for the heterozygote genotype (P = 0.021, the recessive model: 1/2 + 2/2 (P = 0.044 and the minor allele 2 (P = 0.019. The resistance to VL was found to be under the recessive model 1/2 + 2/2 of tumor necrosis factors-β, when comparing VL and DTH + group (odds ratios: 0.558, 95%; confidence interval: 0.316-0.987; P = 0.044. Conclusions: These results must be regarded to preliminary but suggestive that further study with larger populations is worthwhile.

  11. 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.

  12. 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.

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

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    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.

  14. Disease Severity Prediction by Spirometry in Adults with Visceral Leishmaniasis from Minas Gerais, Brazil.

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    Maia, Isabel A; Bezerra, Frank S; Albuquerque, André Luis Pereira de; Andrade, Heitor F; Nicodemo, Antonio C; Amato, Valdir S

    2017-02-08

    Visceral leishmaniasis (VL) is associated with interstitial pneumonitis according to histology and radiology reports. However, studies to address the functional impact on respiratory function in patients are lacking. We assessed pulmonary function using noninvasive spirometry in a cross-sectional study of hospitalized adult VL patients from Minas Gerais, Brazil, without unrelated lung conditions or acute infections. Lung conditions were graded as normal, restrictive, obstructive, or mixed patterns, according to Brazilian consensus standards for spirometry. To control for regional patterns of lung function, we compared spirometry of patients with regional paired controls. Spirometry detected abnormal lung function in most VL patients (70%, 14/20), usually showing a restrictive pattern, in contrast to regional controls and the standards for normal tests. Alterations in spirometry measurements correlated with hypoalbuminemia, the only laboratory value indicative of severity of parasitic disease. Abnormalities did not correlate with unrelated factors such as smoking or occupation. Clinical data including pulmonary symptoms and duration of therapy were also unrelated to abnormal spirometry findings. We conclude that the severity of VL is correlated with a restrictive pattern of lung function according to spirometry, suggesting that there may be interstitial lung involvement in VL. Further studies should address whether spirometry could serve as an index of disease severity in the management of VL. © The American Society of Tropical Medicine and Hygiene.

  15. A potential link among antioxidant enzymes, histopathology and trace elements in canine visceral leishmaniasis

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    Souza, Carolina C; Barreto, Tatiane de O; da Silva, Sydnei M; Pinto, Aldair W J; Figueiredo, Maria M; Ferreira Rocha, Olguita G; Cangussú, Silvia D; Tafuri, Wagner L

    2014-01-01

    Canine visceral leishmaniasis (CVL) is a severe and fatal systemic chronic inflammatory disease. We investigated the alterations in, and potential associations among, antioxidant enzymes, trace elements and histopathology in CVL. Blood and tissue levels of Cu-Zn superoxide dismutase, catalase and glutathione peroxidase were measured in mixed-breed dogs naturally infected with Leishmania infantum chagasi, symptomatic (n = 19) and asymptomatic (n = 11). Serum levels of copper, iron, zinc, selenium and nitric oxide, and plasma lipid peroxidation were measured. Histological and morphometric analyses were conducted of lesions in liver, spleen and lymph nodes. We found lower blood catalase and glutathione peroxidase activity to be correlated with lower iron and selenium respectively. However, higher activity of Cu-Zn superoxide dismutase was not correlated with the increase in copper and decreased in zinc observed in infected animals compared to controls. Organ tissue was characterized by lower enzyme activity in infected dogs than in controls, but this was not correlated with trace elements. Lipid peroxidation was higher in symptomatic than in asymptomatic and control dogs and was associated with lesions such as chronic inflammatory reaction, congestion, haemosiderin and fibrosis. Systemic iron deposition was observed primarily in the symptomatic dogs showing a higher tissue parasite load. Dogs with symptomatic CVL displayed enhanced LPO and Fe tissue deposition associated with decreased levels of antioxidant enzymes. These results showed new points in the pathology of CVL and might open new treatment perspectives associated with antioxidants and the role of iron in the pathogenesis of CVL. PMID:24766461

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

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    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.

  17. 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.

  18. Seroepidemiologic Survey of Canine Visceral Leishmaniasis in Tehran and Alborz Provinces of Iran.

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    Abdolali Malmasi

    2014-12-01

    Full Text Available A two year seroepidemiological study was designed to find out the seroprevalence and risk factors of canine visceral leishmaniasis (CVL among stray and owned dogs in Tehran and Alborz Provinces of Iran.Blood samples of 602 dogs living in 11 counties of Tehran and Alborz Provinces were taken by venipuncture in 2008-2010. After separation of blood sera, anti-leishmanial antibodies were detected by direct agglutination test (DAT.Overall, of the 408 and 194 serum samples collected randomly from dogs in 11 localities in Tehran and Alborz Provinces, 18/408 (4.41% and 12/194 (6.18% respectively were found positive. Among the localities, Shemiran in Tehran Province and Karaj In Alborz Province had the highest prevalence rates. No statistically significant differences were found between sex and living place but there was significant difference between living status (owned or stray and CVL infection of dogs in Alborz Province (P= 0.018. The highest seroprevalence (7.5% was found in dogs aged 3 to 5 years old. Only 20% of the seropositive dogs were symptomatic.Concerning possible human infections in Tehran and Alborz Provinces, both symptomatic and asymptomatic seropositive dogs should be considered as a risk.

  19. NOD2-RIP2-Mediated Signaling Helps Shape Adaptive Immunity in Visceral Leishmaniasis.

    Science.gov (United States)

    Nascimento, Manuela S L; Ferreira, Marcela D; Quirino, Gustavo F S; Maruyama, Sandra R; Krishnaswamy, Jayendra K; Liu, Dong; Berlink, Jonilson; Fonseca, Denise M; Zamboni, Dario S; Carregaro, Vanessa; Almeida, Roque P; Cunha, Thiago M; Eisenbarth, Stephanie S; Silva, João S

    2016-12-01

    Interferon γ (IFN-γ) and interleukin 17A (IL-17A)-producing cells are described to be related to the protection against Leishmania infantum infection. How the immune system coordinates the balance between T-helper type 1 (Th1) and 17 (Th17) responses during visceral leishmaniasis (VL) is still unknown. Here, we combined transcriptional profiling, using RNA sequencing analysis of human samples, with an experimental model to show that Th17-related genes are suppressed and that Th1 signature genes are induced during human VL. The high amount of Th1 cells in VL was dependent on the NOD2-RIP2 signaling in dendritic cells, which was crucial for interleukin 12 production through the phosphorylation of MAPK. On the other hand, this pathway inhibits Th17 cells by limiting interleukin 23 production. As a consequence, Nod2(-/-) and Rip2(-/-) mice showed defects in Th1 responses and higher parasite loads as compared to WT mice. Together, the data demonstrate that the NOD2-RIP2 pathway is activated in murine and human VL and plays a role in shaping adaptive immunity toward a Th1 profile. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  20. A Defective Oxidative Burst and Impaired Antigen Presentation are Hallmarks of Human Visceral Leishmaniasis.

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    Roy, Susmita; Mukhopadhyay, Debanjan; Mukherjee, Shibabrata; Ghosh, Susmita; Kumar, Shishir; Sarkar, Kumkum; Pal, Dipankar; Bhowmik, Pratik; Mandal, Kausik; Modak, Dolanchampa; Guha, Subhasish Kamal; Pramanik, Netai; Goswami, Rama Prosad; Saha, Bibhuti; Chatterjee, Mitali

    2015-01-01

    Survival of the Leishmania parasite within monocytes hinges on its ability to effectively nullify their microbicidal effector mechanisms. Accordingly, this study aimed to delineate this biological niche in patients with visceral leishmaniasis (VL). In monocytes, the redox status, antigen presenting capacity, expression of Toll-like receptors (TLRs), co-stimulatory molecules (CD80/86) and generation of intracellular cytokines (IL-8, IL-1β, IL-10 and LAP-TGF-β1) was measured by flow cytometry, levels of circulating cytokines (IL-1β, IL-6, TNF-α, IL-8, IL-4, IL-13, IL-10 and GM-CSF) by ELISA and arginase activity by spectrophotometry. Within monocytes, generation of an oxidative burst was markedly attenuated as evident by decreased generation of nitric oxide and reactive oxygen species, concomitant with raised levels of thiols. This was accompanied by lowered frequency of TLR4(+) monocytes, but the arginase activity remained unaltered. Pathogen persistence was enhanced by the predominance of anti-inflammatory cytokines within monocytes, notably IL-10. Alongside, development of adaptive immunity was severely attenuated as manifested by a pronounced impairment of antigen presentation and co-stimulation evident by down regulation of CD54, HLA-DR and CD86. Treatment corrected the redox imbalance and reversed the impaired antigen presentation. In VL, monocyte functions were severely impaired facilitating parasite persistence; anti-leishmanial chemotherapy mediated parasite elimination through modulation of the macrophage microenvironment by restoring its redox status and antigen presenting capacity.

  1. Comentario epidemiológico sobre el primer caso colombiano de leishmaniasis visceral

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    Alberto Morales

    1996-01-01

    Full Text Available El primer caso de leishmaniasis visceral demostrado en Colombia fue el de una niña de 37 meses de edad, fallecida en 1943, cuyo hígado, estudiado por viscerotomía, reveló la enfermedad. La paciente vivía en la vereda Chaparral de San Vicente de Chucurí, Santander, y desde entonces se consideró el caso como autóctono de este municipio. Observaciones epidemiológicas, realizadas desde 1972, 29 años después de hecho el diagnóstico, relacionadas con la ecología del vector, con el sitio de nacimiento y la procedencia inicial de la niña, permiten concluir que la paciente adquirió la infección en la vereda San Nicolás del municipio de Lebrija, Santander, área que sí es hábitat adecuado para el desarrollo de Lu.longipalpis, vector de la enfermedad.

  2. First Molecular Characterization of Leishmania Species Causing Visceral Leishmaniasis among Children in Yemen.

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    Mahdy, Mohammed A K; Al-Mekhlafi, Abdulsalam M; Abdul-Ghani, Rashad; Saif-Ali, Reyadh; Al-Mekhlafi, Hesham M; Al-Eryani, Samira M; Lim, Yvonne A L; Mahmud, Rohela

    2016-01-01

    Visceral leishmaniasis (VL) is a debilitating, often fatal disease caused by Leishmania donovani complex; however, it is a neglected tropical disease. L. donovani complex comprises two closely related species, L. donovani that is mostly anthroponotic and L. infantum that is zoonotic. Differentiation between these two species is critical due to the differences in their epidemiology and pathology. However, they cannot be differentiated morphologically, and their speciation using isoenzyme-based methods poses a difficult task and may be unreliable. Molecular characterization is now the most reliable method to differentiate between them and to determine their phylogenetic relationships. The present study aims to characterize Leishmania species isolated from bone marrows of Yemeni pediatric patients using sequence analysis of the ribosomal internal transcribed spacer-1 (ITS1) gene. Out of 41 isolates from Giemsa-stained bone marrow smears, 25 isolates were successfully amplified by nested polymerase chain reaction and sequenced in both directions. Phylogenetic analysis using neighbor joining method placed all study isolates in one cluster with L. donovani complex (99% bootstrap). The analysis of ITS1 for microsatellite repeat numbers identified L. infantum in 11 isolates and L. donovani in 14 isolates. These data suggest the possibility of both anthroponotic and zoonotic transmission of VL-causing Leishmania species in Yemen. Exploring the possible animal reservoir hosts is therefore needed for effective control to be achieved.

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

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    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.

  4. 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.

  5. 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.

  6. 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.

  7. 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. 

  8. A Mathematical Study to Control Visceral Leishmaniasis: An Application to South Sudan.

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    Ghosh, Indrajit; Sardar, Tridip; Chattopadhyay, Joydev

    2017-05-01

    In this manuscript, we propose and analyze a compartmental model of visceral leishmaniasis (VL). We model the human population with six compartments including asymptomatic, symptomatic and PKDL-infected, animal population as second host and sandfly population as the vector. Furthermore, the non-adult stage of the sandfly population is introduced in the system, which was not considered before in the literature. We show that the increase in the number of host of sandfly population generates a backward bifurcation. Thus, multiple hosts will cause disease persistence even if the basic reproduction number ([Formula: see text]) is below unity. We perform a sensitivity analysis of important model parameters with respect to some epidemiologically significant responses. We validate our model by calibrating it to weekly VL incidence data from South Sudan for the year 2013. We perform cost-effectiveness analysis on different interventions: treatment, non-adult control, adult control and their different layered combinations based on their implementation cost (in USD) and case reduction. We also use a global sensitivity analysis technique to understand the effect of important parameters of our model on the implementation cost of different controls. This cost-effectiveness study and cost-sensitivity analysis are relatively new in existing literature of this disease.

  9. 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.

  10. 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)

  11. 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

  12. 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.

  13. 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 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

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

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    Távora, Lara Gurgel Fernandes; Nogueira, Marina Bizerril; Gomes, Sofia Teixeira

    2015-01-01

    Since the beginning of the HIV burden, Visceral Leishmaniasis (VL)/HIV co-infection has been diagnosed not only in areas where VL is endemic (Latin America, India, Asia, Southern Europe), but also in North America, were it is considered an opportunistic disease. Clinical presentation, diagnostic tests sensitivity and treatment response in this population differs from VL alone. To evaluate factors related to an unfavorable outcome in patients with VL/HIV diagnosis in a reference center in northeast Brazil. Co-infected patients, diagnosed from 2010 to 2012, were included. Data from medical records were collected until one year after VL treatment completion. Forty-two HIV-infected patients were included in the study. Anemia, leukopenia, and thrombocytopenia were present in 95%, 70.7%, and 63.4%, respectively. Mean T CD4+ (LTCD4) lymphocyte count was 183 cells/dL. Highly active antiretroviral therapy (HAART) was being used by 54.7% of cases. A favorable outcome was seen in 71.4% of cases. Recurrence of VL occurred in nine patients and deaths were secondary to infectious complications (3/42 patients). Very low LTCD4 count (LTCD4 count at presentation was associated with unfavorable outcome in VL/HIV patients. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

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

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    Lara Gurgel Fernandes Távora

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

  16. Epidemiological and immunological aspects of human visceral leishmaniasis on Margarita Island, Venezuela.

    Science.gov (United States)

    Zerpa, Olga; Ulrich, Marian; Benitez, Margarita; Avila, Concepción; Rodríguez, Vestalia; Centeno, Marta; Belizario, Doris; Reed, Steven G; Convit, Jacinto

    2002-12-01

    Sixty-five patients were diagnosed with visceral leishmaniasis (VL) on Margarita Island in the decade from 1990 to1999; 86.2% were <= 3 years old. All were leishmanin-negative at diagnosis. Evaluation of 23 cured patients in 1999 revealed that 22/23 had converted to leishmanin-positive; five had persisting antibodies to rK39 antigen, with no clinical evidence of disease. Leishmanin tests were positive in 20.2% of 1,643 healthy individuals from 417 households in endemic areas. Of the positive reactors, 39.8% were identified in 35 (8.4%) of the households, 15 of which had an antecedent case of VL, a serologically positive dog or both. Weak serological activity to rK39 antigen was detected in 3 of 488 human sera from the endemic areas. The presence of micro-foci of intense peri-urban transmission and the apparent absence of other Trypanosomatidae causing human disease offer a unique opportunity for the study of reservoirs, alternative vectors and evaluation of control measures on the Island.

  17. The economic impact of visceral leishmaniasis on rural households in one endemic district of Bihar, India.

    Science.gov (United States)

    Sarnoff, Rhonda; Desai, Jaikishan; Desjeux, Philippe; Mittal, Atul; Topno, Roshan; Siddiqui, Niyamat Ali; Pandey, Arvind; Sur, Dipika; Das, Pradeep

    2010-07-01

    To estimate the economic burden of visceral leishmaniasis (VL) on the rural population of one VL endemic district of Bihar, the state with 85% of India's cases. Using a survey of a stratified multistage sampling of 15 178 households with 214 individuals with VL in the previous 12 months, the study provides data on VL treatment expenditures, financing and days of work lost in the context of overall household expenditures, income sources and assets. Median household expenditures on VL treatment represent, on average, 11% of annual household expenditures and an estimated 7 months of an individual's income at the daily wage in rural Bihar. With 87% of households forced to take out loans to finance disease costs, VL can contribute to a spiral of increasing poverty. The current pattern of VL treatment, with multiple visits and treatments for a single episode of illness, significantly increases the economic burden on the household. India's National Elimination Program to make effective treatments accessible to the rural poor, if combined with expanded efforts to improve timely access to diagnosis by conducting rapid diagnostic tests closer to the community (and mobilizing the rural population to seek effective treatment earlier), can reduce VL's economic burden on India's rural households.

  18. American visceral leishmaniasis: disease control strategies in dracen microregion in alta paulista, SP, Brazil

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    LAZ D'Andrea

    2009-01-01

    Full Text Available Despite measures adopted to control American visceral leishmaniasis (AVL, the disease is spreading in a fast and worrying way throughout western São Paulo state. The aim of this work was to study the variables involved in the disease cycle as well as the effectiveness of controlling measures. The study was carried out in the microregion of Dracena, which is composed of twelve cities and belongs to Alta Paulista, a region of western São Paulo. The necessary data were provided by the Superintendence for Endemic Disease Control and Adolfo Lutz Institute, Regional Laboratory of Presidente Prudente. From August 2005 to January 2008, the following factors were observed: detection of phlebotomine sandflies in the cities and periods in which dogs or humans were diagnosed; number of human deaths; prevalence of suspected dogs tested by serology; percentage of euthanasia in suspected dogs; a possible correlation between positive dogs and cases of the disease in humans; and the disease prevalence among municipalities from the studied region. It was verified that, despite the strategies adopted in Dracena microregion to control AVL, the disease continues to rise. Thus, some procedures of the AVL Monitoring and Control Program should be reviewed, to grant the initiative more credibility and effectiveness.

  19. 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.

  20. Surface-Modified Liposomal Formulation of Amphotericin B: In vitro Evaluation of Potential Against Visceral Leishmaniasis.

    Science.gov (United States)

    Patere, Shilpa N; Pathak, Pankaj O; Kumar Shukla, Anil; Singh, Rajesh Kumar; Kumar Dubey, Vikash; Mehta, Miten J; Patil, Anand G; Gota, Vikram; Nagarsenker, Mangal S

    2017-04-01

    Surface modification of liposomes with targeting ligands is known to improve the efficacy with reduced untoward effects in treating infective diseases like visceral leishmaniasis (VL). In the present study, modified ligand (ML), designed by modifying polysaccharide with a long chain lipid was incorporated in liposomes with the objective to target amphotericin B (Amp B) to reticuloendothelial system and macrophages. Conventional liposomes (CL) and surface modified liposomes (SML) were characterized for size, shape, and entrapment efficiency (E.E.). Amp B SML with 3% w/w of ML retained the vesicular nature with particle size of ∼205 nm, E.E. of ∼95% and good stability. SML showed increased cellular uptake in RAW 264.7 cells which could be attributed to receptor-mediated endocytosis. Compared to Amp B solution, Amp B liposomes exhibited tenfold increased safety in vitro in RAW 264.7 and J774A.1 cell lines. Pharmacokinetics and biodistribution studies revealed high t 1/2, area under the curve (AUC)0-24, reduced clearance and prolonged retention in liver and spleen with Amp B SML compared to other formulations. In promastigote and amastigote models, Amp B SML showed enhanced performance with low 50% inhibitory concentration (IC50) compared to Amp B solution and Amp B CL. Thus, due to the targeting ability of ML, SML has the potential to achieve enhanced efficacy in treating VL.

  1. 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 (p<0.047) while in dogs younger than 1year was 12% (95% CI: 6-18%), in 1-2 years 10% (95% CI: 6-14%), in 3-5 years 16% (95% CI: 9-22%) and in those which were over 7 years 31% (95% CI: 19-44%), respectively. Our meta- regression analysis revealed the significant correlation between stray and owned dogs: the infection rate in stray 10% (95% CI: 5-4%) was higher than those owned 6% (95% CI: 3- 8%) (p=0.037). Also, the prevalence of infection in rural dogs 36% (95% CI: -1-72%) is significantly higher than urban dogs, 19% (95% CI:-1-40%) (p=0.013). Although most (81%) of infected dogs had no clinical signs (asymptomatic), meta-regression analysis showed that the infection rate in

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Visceral Leishmaniasis Unresponsive to Pentostam Caused by Leishmania tropica in Kenya

    Science.gov (United States)

    1989-01-01

    leishmaniasis in the Old World. the opposite end. Somewhere in the middle lies has been isolated from a small number of pa- the erosive mucocutaneous form...parasite is thought to cause of leishmaniasis respond to treatment with Sbv. human Americ. i cutaneous leishmaniasis . which Mucocutaneous and diffuse... LEISHMANIASIS UNRESPONSIVE TO PENTOSTAM CAUSED BY LEISHMANIA TROPIC IN KENYA YEMANE MEBRAHTU, PHILLIP LAWYER. JOHN GITHURE. JOAB B. WERE, RICHARD MUIGAI

  7. Surveillance of canine visceral leishmaniasis in a disease-free area Vigilância da leishmaniose visceral canina em área indene

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    Michele Salmon Frehse

    2010-03-01

    Full Text Available Leishmaniasis is an important re-emergent parasitosis worldwide, particularly in tropical countries. There are no reports of autochthonous disease in the State of Paraná, southern Brazil. No surveillance has been carried out in the most populated areas such as the city of Curitiba and its surroundings. The purpose of the present study was to determine the seroprevalence of visceral leishmaniasis in dogs at the Center for Zoonosis Control of São José dos Pinhais, Paraná, before euthanasia. Enzyme-linked immunosorbent assay (ELISA and immunofluorescence antibody test (IFAT were used to detect antibody levels against Leishmania sp. in dog sera. Imprints of the popliteal lymph nodes that were also randomly collected from 50 dogs with suspected clinical signs of visceral leishmaniasis, and evaluated under light microscopy for the detection of amastigote forms, were negative. A total of 364 dog samples were tested. The results showed only one positive sample (0.0027% by ELISA test but negative by IFAT, however, the dog had no clinical signs. Random surveillance of dog populations from several districts of a metropolitan area may be a means of preventing Leishmania spreading. Based on our results, the city of Curitiba and its metropolitan area were considered at low risk for visceral leishmaniasis.A leishmaniose é uma importante parasitose re-emergente observada no mundo, particularmente em países tropicais. Não há ainda relatos de casos autóctones no estado do Paraná. Não há até o momento referência de vigilância no reservatório canino, tais como Curitiba e região metropolitana do estado. O objetivo do estudo foi determinar a soroprevalência da leishmaniose visceral em cães entregues ao Centro de Controle de Zoonoses de São José dos Pinhais, Paraná para eutanásia. A detecção sorológica da presença de anticorpos contra Leishmania sp. foi realizada por (ELISA indireto e pela Reação de Imunofluorescência Indireta (RIFI. Al

  8. Visceral leishmaniasis in congenic mice of susceptible and resistant phenotypes: immunosuppression by adherent spleen cells.

    Science.gov (United States)

    Nickol, A D; Bonventre, P F

    1985-10-01

    Visceral leishmaniasis is one of several parasitic diseases of humans characterized by immune suppression. A murine model of disseminated leishmaniasis utilizing inbred strains of specific genetic constitution was used to study the mechanisms of immunosuppression elicited during the course of infection. Resistant (Lshr) and susceptible (Lshs) strains of mice were challenged with amastigotes of Leishmania donovani and evaluated as to immune status at intervals between 2 and 40 weeks after challenge. The proliferative responses of splenic lymphocytes to T-cell mitogens, a B-cell mitogen, and parasite antigens were measured to evaluate the relative immune status of parasitized mice and noninfected control mice. Lymphocytes from resistant C3Heb/FeJ (C3H) mice responded normally to concanavalin A and phytohemagglutinin throughout the course of infection. Parasite antigen responses appeared 2 weeks after challenge of C3H mice and remained vigorous for periods up to 6 months. In contrast, immune suppression during infection was profound in both the curing (C57B1/10) and noncuring (B10.D2) phenotypes of Lshs congenic mice. Both Lshs strains developed severe infection as evidenced by high parasite burdens in the liver and spleen 4 to 5 weeks after challenge; splenic lymphocytes taken from these mice between 2 and 8 weeks became increasingly unresponsive to the T-cell mitogens as well as to parasite antigens. The noncuring B10.D2 mice which suffered chronic infection continued to be suppressed for as long as 40 weeks. C57B1/10 (curing) mice, in contrast, cleared infection between 12 and 16 weeks. After spontaneous recovery or elimination of parasites by antimonial drug therapy, the response of spleen cells to T-cell mitogens or parasite antigens were restored to normal. The spleen cells from the Lshs strains of mice obtained during the height of infection suppressed the proliferative responses of spleen cells from their uninfected counterparts upon cocultivation in vitro

  9. Th1-biased immunomodulation and therapeutic potential of Artemisia annua in murine visceral leishmaniasis.

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    Mohammad Islamuddin

    2015-01-01

    Full Text Available In the absence of vaccines and limitations of currently available chemotherapy, development of safe and efficacious drugs is urgently needed for visceral leishmaniasis (VL that is fatal, if left untreated. Earlier we reported in vitro apoptotic antileishmanial activity of n-hexane fractions of Artemisia annua leaves (AAL and seeds (AAS against Leishmania donovani. In the present study, we investigated the immunostimulatory and therapeutic efficacy of AAL and AAS.Ten-weeks post infection, BALB/c mice were orally administered AAL and AAS for ten consecutive days. Significant reduction in hepatic (86.67% and 89.12% and splenic (95.45% and 95.84% parasite burden with decrease in spleen weight was observed. AAL and AAS treated mice induced the strongest DTH response, as well as three-fold decrease in IgG1 and two-fold increase in IgG2a levels, as compared to infected controls. Cytometric bead array further affirmed the elicitation of Th1 immune response as indicated by increased levels of IFN-γ, and low levels of Th2 cytokines (IL-4 and IL-10 in serum as well as in culture supernatant of lymphocytes from treated mice. Lymphoproliferative response, IFN-γ producing CD4+ and CD8+ T lymphocytes and nitrite levels were significantly enhanced upon antigen recall in vitro. The co-expression of CD80 and CD86 on macrophages was significantly augmented. CD8+ T cells exhibited CD62Llow and CD44hi phenotype, signifying induction of immunological memory in AAL and AAS treated groups. Serum enzyme markers were in the normal range indicating inertness against nephro- and hepato-toxicity.Our results establish the two-prong antileishmanial efficacy of AAL and AAS for cure against L. donovani that is dependent on both the direct leishmanicidal action as well as switching-on of Th1-biased protective cell-mediated immunity with generation of memory. AAL and AAS could represent adjunct therapies for the treatment of leishmaniasis, either alone or in combination with

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

    Science.gov (United States)

    Costa, Lourena Emanuele; Goulart, Luiz Ricardo; Pereira, Nathália Cristina de Jesus; Lima, Mayara Ingrid Sousa; Duarte, Mariana Costa; Martins, Vivian Tamietti; Lage, Paula Sousa; Menezes-Souza, Daniel; Ribeiro, Tatiana Gomes; Melo, Maria Norma; Fernandes, Ana Paula; Soto, Manuel; Tavares, Carlos Alberto Pereira; Chávez-Fumagalli, Miguel Angel; Coelho, Eduardo Antonio Ferraz

    2014-01-01

    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. 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. 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 parasite burden. This is the first study that describes phage-displayed peptides as

  11. 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

  12. Effectiveness and Safety of Short Course Liposomal Amphotericin B (AmBisome) as First Line Treatment for Visceral Leishmaniasis in Bangladesh

    Science.gov (United States)

    Lucero, Emiliano; Collin, Simon M.; Gomes, Sujit; Akter, Fatima; Asad, Asaduzzam; Kumar Das, Asish; Ritmeijer, Koert

    2015-01-01

    Background Bangladesh is one of the endemic countries for Visceral Leishmaniasis (VL). Médecins Sans Frontières (MSF) ran a VL treatment clinic in the most endemic district (Fulbaria) between 2010 and 2013 using a semi-ambulatory regimen for primary VL of 15mg/kg Liposomal Amphotericin-B (AmBisome) in three equal doses of 5mg/kg. The main objective of this study was to analyze the effectiveness and safety of this regimen after a 12 month follow-up period by retrospective analysis of routinely collected program data. A secondary objective was to explore risk factors for relapse. Methods and Principal Findings Our analysis included 1521 patients who were initially cured, of whom 1278 (84%) and 1179 (77.5%) were followed-up at 6 and 12 months, respectively. Cure rates at 6 and 12 months were 98.7% (1262/1278) and 96.4% (1137/1179), respectively. Most relapses (26/39) occurred between 6 and 12 months after treatment. Serious adverse events (SAE) were recorded for 7 patients (0.5%). Odds of relapse at 12 months were highest in the youngest and oldest age groups. There was some evidence that spleen size measured on discharge (one month after initiation of treatment) was associated with risk of relapse: OR=1.25 (95% CI 1.01 to 1.55) per cm below lower costal margin (P=0.04). Conclusions Our study demonstrates that 15mg/kg AmBisome in three doses of 5mg/kg is an effective (>95% cure rate) and safe (<1% SAE) treatment for primary VL in Bangladesh. The majority of relapses occurred between 6 and 12 months, justifying the use of a longer follow-up period when feasible. Assessment of risk of relapse based on easily measured clinical parameters such as spleen size could be incorporated in VL treatment protocols in resource-poor settings where test-of-cure is not always feasible. PMID:25837313

  13. Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis.

    Science.gov (United States)

    Nico, Dirlei; Maran, Naiara; Santos, Leonardo; Ramos-Junior, Erivan Schnaider; Mantuano, Natália Rodrigues; Coutinho, Joseane Lima Prado; Vale, Andre Macedo; Freire-de-Lima, Celio Geraldo; Todeschini, Adriane; Rodrigues, Juliany Cola Fernandes; Palatnik-de-Sousa, Clarisa Beatriz; Morrot, Alexandre

    2015-02-19

    Leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania protozoa that are transmitted to mammalian hosts by infected sand flies. Infection is associated with distinct clinical manifestations that include cutaneous, mucocutaneous and visceral lesions. Visceral leishmaniasis (VL) is the most severe form of the disease and is considered second in terms of mortality and fourth in terms of morbidity among tropical diseases. IFN-γ-producing T cells are involved in protection against the disease. CD43⁺/⁺ and CD43⁻/⁻ mice on a C57BL/6 background were intravenously injected with 5 × 10 ⁷ amastigotes of Leishmania (L.) infantum chagasi, and 30 days after infection the clinical signs of disease were examined; the splenocytes were isolated and assayed for cytokine production; and the livers were removed for phenotypic analysis of T cell subsets by flow cytometry. We report that mice lacking CD43 display increased susceptibility to infection by Leishmania (L.) infantum chagasi, with higher parasite burdens than wild-type mice. The increased susceptibility of CD43⁻/⁻ mice were associated with a weakened delayed hypersensitivity response and reduced levels of IgG2a antibodies to leishmania antigens. We further showed that expression of CD43 defines a major intrahepatic CD4⁺ and CD8⁺ T cell subsets with pro-inflammatory phenotypes and leads to increased levels of IFN-γ secretion by activated splenocytes. Our findings point to a role of CD43 in the development of host resistance to visceral leishmaniasis.

  14. 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.

  15. Identification of an immunodominant 32-kilodalton membrane protein of Leishmania donovani infantum promastigotes suitable for specific diagnosis of Mediterranean visceral leishmaniasis.

    OpenAIRE

    Tebourski, F; el Gaied, A; Louzir, H; Ben Ismail, R; Kammoun, R; Dellagi, K

    1994-01-01

    Sera from 35 patients suffering from Mediterranean visceral leishmaniasis (caused by Leishmania donovani infantum) and 59 patients with various forms of cutaneous leishmaniasis prevalent in the sub-Mediterranean countries (caused by Leishmania major, L. donovani infantum, or Leishmania tropica) were tested by immunoblotting and enzyme-linked immunosorbent assay (ELISA) with both membrane and soluble antigens prepared from L. donovani infantum parasites. Control sera were from healthy children...

  16. Epidemiologic surveillance of canine visceral leishmaniasis in the municipality of Recife, Pernambuco Vigilância epidemiológica de leishmaniose visceral canina no município de Recife, Pernambuco

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    Filipe Dantas-Torres

    2005-10-01

    Full Text Available This paper describes an epidemiologic investigation carried out in Imbiribeira district, where a canine visceral leishmaniasis case was recorded. Despite the absence of seropositive dogs and sand flies, these findings are not sufficient to discard the occurrence of a zoonotic cycle of visceral leishmaniasis in Recife.Este artigo descreve uma investigação epidemiológica realizada no bairro da Imbiribeira, onde fora registrado um caso de leishmaniose visceral canina. Apesar da ausência de cães soropositivos e de flebotomíneos, esses achados não são suficientes para descartar a ocorrência do ciclo zoonótico da leishmaniose visceral em Recife.

  17. Sandflies (Diptera: Psychodidae in a focus of visceral leishmaniasis in White Nile, Sudan

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    Sally Osman Widaa

    2012-06-01

    Full Text Available Visceral leishmaniasis (VL has been known to occur since the 1980s on the western bank of the White Nile River (Central Sudan, 150 km south of Khartoum, and has resulted in high mortality. The most recent outbreak of the disease in this area began in 2006. Entomological surveys were carried out during May 2008, June 2010 and May and July 2011 in the White Nile area. Sandflies were collected using Centers for Disease Control light traps and sticky oil traps in the village of Kadaba and the nearby woodland. Phlebotomus females were dissected for the presence of Leishmania promastigotes. A total of 17,387 sandflies, including six species of Phlebotomus and 10 species of Sergentomyia, were identified. The Phlebotomus species recorded were Phlebotomus orientalis, Phlebotomus papatasi, Phlebotomus bergeroti, Phlebotomus duboscqi, Phlebotomus rodhaini and Phlebotomus saevus. P. orientalis was collected in both habitats. The relative abundance of P. orientalis in the woodland habitat was higher than that recorded in the village habitat. In the woodland habitat, there was a notable increase in the relative abundance of P. orientalis during the surveys conducted in 2008 and 2010 compared to 2011. None of the 311 P. orientalis females dissected were infected with Leishmania promastigotes, although relatively high parous rates were recorded in both habitats. Based on the distribution of P. orientalis recorded in this study, this species is the most likely vector of VL in the endemic focus in the White Nile area. Further investigation is required to elucidate the seasonal abundance and distribution of the vector, as well as the transmission season of VL in both habitats so that appropriate control strategies for the vector can be designed.

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

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    Dirceu Joaquim Costa

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

  19. Knockdown resistance mutations predict DDT resistance and pyrethroid tolerance in the visceral leishmaniasis vector Phlebotomus argentipes.

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    Bruno Gomes

    2017-04-01

    Full Text Available Indoor residual spraying (IRS with DDT has been the primary strategy for control of the visceral leishmaniasis (VL vector Phlebotomus argentipes in India but efficacy may be compromised by resistance. Synthetic pyrethroids are now being introduced for IRS, but with a shared target site, the para voltage-gated sodium channel (VGSC, mutations affecting both insecticide classes could provide cross-resistance and represent a threat to sustainable IRS-based disease control.A region of the Vgsc gene was sequenced in P. argentipes from the VL hotspot of Bihar, India. Two knockdown resistance (kdr mutations were detected at codon 1014 (L1014F and L1014S, each common in mosquitoes, but previously unknown in phlebotomines. Both kdr mutations appear largely recessive, but as homozygotes (especially 1014F/F or as 1014F/S heterozygotes exert a strong effect on DDT resistance, and significantly predict survivorship to class II pyrethroids in short-duration bioassays. The mutations are present at high frequency in wild P. argentipes populations from Bihar, with 1014F significantly more common in higher VL areas.The Vgsc mutations detected appear to be a primary mechanism underlying DDT resistance in P. argentipes and a contributory factor in reduced pyrethroid susceptibility, suggesting a potential impact if P. argentipes are subjected to suboptimal levels of pyrethroid exposure, or additional resistance mechanisms evolve. The assays to detect kdr frequency changes provide a sensitive, high-throughput monitoring tool to detecting spatial and temporal variation in resistance in P. argentipes.

  20. Insecticide susceptibility of Phlebotomus argentipes in visceral leishmaniasis endemic districts in India and Nepal.

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    Diwakar Singh Dinesh

    Full Text Available OBJECTIVES: To investigate the DDT and deltamethrin susceptibility of Phlebotomus argentipes, the vector of Leishmania donovani, responsible for visceral leishmaniasis (VL, in two countries (India and Nepal with different histories of insecticide exposure. METHODS: Standard WHO testing procedures were applied using 4% DDT and 0.05% deltamethrin impregnated papers. The effect of the physiological status (fed and unfed of females on the outcome of the bioassays was assessed and the optimal time of exposure for deltamethrin was evaluated on a colony population. Field populations from both countries were tested. RESULTS: Fed and unfed females responded in a similar way. For exposure time on field samples 60 min was adopted for both DDT and deltamethrin. In Bihar, knockdown and mortality with DDT was respectively 20 and 43%. In Nepal almost all sand flies were killed, except at the border with Bihar (mortality 62%. With 0.05% deltamethrin, between 96 and 100% of the sand flies were killed in both regions. CONCLUSIONS: Based on literature and present data 4% DDT and 0.05% deltamethrin seem to be acceptable discriminating concentrations to separate resistant from susceptible populations. Resistance to DDT was confirmed in Bihar and in a border village of Nepal, but the sand flies were still susceptible in villages more inside Nepal where only synthetic pyrethroids are used for indoor spraying. The low effectiveness of indoor spraying with DDT in Bihar to control VL can be partially explained by this resistance hence other classes of insecticides should be tested. In both countries P. argentipes sand flies were susceptible to deltamethrin.

  1. Insecticide susceptibility of Phlebotomus argentipes in visceral leishmaniasis endemic districts in India and Nepal.

    Science.gov (United States)

    Dinesh, Diwakar Singh; Das, Murari Lal; Picado, Albert; Roy, Lalita; Rijal, Suman; Singh, Shri Prakash; Das, Pradeep; Boelaert, Marleen; Coosemans, Marc

    2010-10-26

    To investigate the DDT and deltamethrin susceptibility of Phlebotomus argentipes, the vector of Leishmania donovani, responsible for visceral leishmaniasis (VL), in two countries (India and Nepal) with different histories of insecticide exposure. Standard WHO testing procedures were applied using 4% DDT and 0.05% deltamethrin impregnated papers. The effect of the physiological status (fed and unfed) of females on the outcome of the bioassays was assessed and the optimal time of exposure for deltamethrin was evaluated on a colony population. Field populations from both countries were tested. Fed and unfed females responded in a similar way. For exposure time on field samples 60 min was adopted for both DDT and deltamethrin. In Bihar, knockdown and mortality with DDT was respectively 20 and 43%. In Nepal almost all sand flies were killed, except at the border with Bihar (mortality 62%). With 0.05% deltamethrin, between 96 and 100% of the sand flies were killed in both regions. Based on literature and present data 4% DDT and 0.05% deltamethrin seem to be acceptable discriminating concentrations to separate resistant from susceptible populations. Resistance to DDT was confirmed in Bihar and in a border village of Nepal, but the sand flies were still susceptible in villages more inside Nepal where only synthetic pyrethroids are used for indoor spraying. The low effectiveness of indoor spraying with DDT in Bihar to control VL can be partially explained by this resistance hence other classes of insecticides should be tested. In both countries P. argentipes sand flies were susceptible to deltamethrin.

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

    Science.gov (United States)

    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.

  3. 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.

  4. Serum soluble markers in the evaluation of treatment in human visceral leishmaniasis.

    Science.gov (United States)

    Schriefer, A; Barral, A; Carvalho, E M; Barral-Netto, M

    1995-12-01

    Visceral leishmaniasis (VL) has a fatal course if not properly treated. Recovery from VL is linked to cellular immune response. Unresponsiveness to antimonial therapy reinforces the importance of determining parameters for treatment assessment. We analysed the pre- and post-treatment serum levels of soluble CD4 (sCD4), sCD8, sIL-2R, soluble intercellular adhesion molecule-1 (sICAM-1) and neopterin in groups of VL patients either responsive or not to standard antimonial therapy. Pretreatment serum levels of all markers except for sICAM-1 were significantly higher in VL patients than in healthy subjects from the same area (P antimonial therapy (P = 0.25), but significantly higher in patients responsive to treatment (P = 0.02). The comparison of pre- and post-treatment concentrations showed that all markers, except sCD4 and sICAM-1, presented a significant fall (P antimonial therapy. However, only neopterin presented with levels compatible with those of healthy subjects at the end of treatment (P = 0.30). In refractory patients sICAM-1 presented with post-treatment levels significantly higher than the pretreatment determinations (P = 0.03), while sCD4 experienced a significant drop (P = 0.01). All markers displayed clearly distinct behaviour according to the patient's response to therapy. This makes all soluble molecules studied suitable for use as indicators of antimonial therapy response. Additionally the comparison of pretreatment levels of the markers between responders and refractory patients to antimonial therapy showed that serum concentrations of sIL-2R and sICAM-1 significantly differed among these two groups (P = 0.02 in each case), suggesting that they may be used in future as predictors of antimonial therapy response.

  5. Serum soluble markers in the evaluation of treatment in human visceral leishmaniasis.

    Science.gov (United States)

    Schriefer, A; Barral, A; Carvalho, E M; Barral-Netto, M

    1995-01-01

    Visceral leishmaniasis (VL) has a fatal course if not properly treated. Recovery from VL is linked to cellular immune response. Unresponsiveness to antimonial therapy reinforces the importance of determining parameters for treatment assessment. We analysed the pre- and post-treatment serum levels of soluble CD4 (sCD4), sCD8, sIL-2R, soluble intercellular adhesion molecule-1 (sICAM-1) and neopterin in groups of VL patients either responsive or not to standard antimonial therapy. Pretreatment serum levels of all markers except for sICAM-1 were significantly higher in VL patients than in healthy subjects from the same area (P antimonial therapy (P = 0.25), but significantly higher in patients responsive to treatment (P = 0.02). The comparison of pre- and post-treatment concentrations showed that all markers, except sCD4 and sICAM-1, presented a significant fall (P antimonial therapy. However, only neopterin presented with levels compatible with those of healthy subjects at the end of treatment (P = 0.30). In refractory patients sICAM-1 presented with post-treatment levels significantly higher than the pretreatment determinations (P = 0.03), while sCD4 experienced a significant drop (P = 0.01). All markers displayed clearly distinct behaviour according to the patient's response to therapy. This makes all soluble molecules studied suitable for use as indicators of antimonial therapy response. Additionally the comparison of pretreatment levels of the markers between responders and refractory patients to antimonial therapy showed that serum concentrations of sIL-2R and sICAM-1 significantly differed among these two groups (P = 0.02 in each case), suggesting that they may be used in future as predictors of antimonial therapy response. PMID:8536369

  6. Evaluation of a prototype flow cytometry test for serodiagnosis of canine visceral leishmaniasis.

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    Ker, Henrique Gama; Coura-Vital, Wendel; Aguiar-Soares, Rodrigo Dian de Oliveira; Roatt, Bruno Mendes; das Dores Moreira, Nádia; Carneiro, Cláudia Martins; Machado, Evandro Marques de Menezes; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Giunchetti, Rodolfo Cordeiro; Araújo, Márcio Sobreira Silva; Coelho, Eduardo Antonio Ferraz; da Silveira-Lemos, Denise; Reis, Alexandre Barbosa

    2013-12-01

    Diagnosing canine visceral leishmaniasis (CVL) is a critical challenge since conventional immunoserological tests still present some deficiencies. The current study evaluated a prototype flow cytometry serology test, using antigens and fluorescent antibodies that had been stored for 1 year at 4°C, on a broad range of serum samples. Noninfected control dogs and Leishmania infantum-infected dogs were tested, and the prototype test showed excellent performance in differentiating these groups with high sensitivity, specificity, positive and negative predictive values, and accuracy (100% in all analyses). When the CVL group was evaluated according to the dogs' clinical status, the prototype test showed outstanding accuracy in all groups with positive serology (asymptomatic II, oligosymptomatic, and symptomatic). However, in dogs which had positive results by PCR-restriction fragment length polymorphism (RFLP) but negative results by conventional serology (asymptomatic I), serological reactivity was not observed. Additionally, sera from 40 dogs immunized with different vaccines (Leishmune, Leish-Tec, or LBSap) did not present serological reactivity in the prototype test. Eighty-eight dogs infected with other pathogens (Trypanosoma cruzi, Leishmania braziliensis, Ehrlichia canis, and Babesia canis) were used to determine cross-reactivity and specificity, and the prototype test performed well, particularly in dogs infected with B. canis and E. canis (100% and 93.3% specificities, respectively). In conclusion, our data reinforce the potential of the prototype test for use as a commercial kit and highlight its outstanding performance even after storage for 1 year at 4°C. Moreover, the prototype test efficiently provided accurate CVL serodiagnosis with an absence of false-positive results in vaccinated dogs and minor cross-reactivity against other canine pathogens.

  7. B Cell: T Cell Interactions Occur within Hepatic Granulomas during Experimental Visceral Leishmaniasis

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    Moore, John W. J.; Beattie, Lynette; Dalton, Jane E.; Owens, Benjamin M. J.; Maroof, Asher; Coles, Mark C.; Kaye, Paul M.

    2012-01-01

    Hepatic resistance to Leishmania donovani infection in mice is associated with the development of granulomas, in which a variety of lymphoid and non-lymphoid populations accumulate. Although previous studies have identified B cells in hepatic granulomas and functional studies in B cell-deficient mice have suggested a role for B cells in the control of experimental visceral leishmaniasis, little is known about the behaviour of B cells in the granuloma microenvironment. Here, we first compared the hepatic B cell population in infected mice, where ≈60% of B cells are located within granulomas, with that of naïve mice. In infected mice, there was a small increase in mIgMlomIgD+ mature B2 cells, but no enrichment of B cells with regulatory phenotype or function compared to the naïve hepatic B cell population, as assessed by CD1d and CD5 expression and by IL-10 production. Using 2-photon microscopy to quantify the entire intra-granuloma B cell population, in conjunction with the adoptive transfer of polyclonal and HEL-specific BCR-transgenic B cells isolated from L. donovani-infected mice, we demonstrated that B cells accumulate in granulomas over time in an antigen-independent manner. Intra-vital dynamic imaging was used to demonstrate that within the polyclonal B cell population obtained from L. donovani-infected mice, the frequency of B cells that made multiple long contacts with endogenous T cells was greater than that observed using HEL-specific B cells obtained from the same inflammatory environment. These data indicate, therefore, that a subset of this polyclonal B cell population is capable of making cognate interactions with T cells within this unique environment, and provide the first insights into the dynamics of B cells within an inflammatory site. PMID:22479545

  8. 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.

  9. 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.

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

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

    2014-01-01

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

  12. Clinical aspects of paediatric visceral leishmaniasis in North-west Ethiopia.

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    Diro, Ermias; Lynen, Lutgarde; Gebregziabiher, Berhane; Assefa, Abraham; Lakew, Wubishet; Belew, Zewdu; Hailu, Asrat; Boelaert, Marleen; van Griensven, Johan

    2015-01-01

    Visceral leishmaniasis (VL) in north-west Ethiopia is causing an overwhelming case load among adult migrant workers that masked the disease burden in children. This study describes the clinical profile and explores comorbidities in paediatric VL patients. A prospective study at two hospitals in this region (Gondar and Humera) was conducted in a year period, 2011-2012. The clinical manifestations and comorbidities such as malnutrition, intestinal parasitosis and vitamin D deficiency and HIV infection were assessed, and treatment outcomes noted. A total of 122 children with VL were detected during the study period with median age of 8.5 years (IQR 5-12 years); 23% were under 5 years. Eighty-five (69.7%) cases were male. The clinical manifestations were similar to the adult patients. High rates of malnutrition, intestinal parasitosis (47.5%) and hypovitaminosis D (56.4%) were detected. The proportion of stunting and wasting was 63% and 22.2% in children aged under five years, and 50.5% and 75.9% in 5-year and older children, respectively, using WHO standard growth curves. Only one child had HIV infection. In 95% of the cases, sodium stibogluconate (20 mg/kg/day for 30 days) was used for treatment. The treatment success rate at end of therapy was 98.3%, but the definitive outcome at 6 months could not be determined because of a high loss to follow-up (80.2%). While HIV co-infection was rare, malnutrition, intestinal parasitosis and vitamin D deficiency were frequent indicating the need for further research on their role in the pathophysiology. Meanwhile, systematic assessment and management of malnutrition and intestinal parasitosis in VL programmes is recommended. © 2014 John Wiley & Sons Ltd.

  13. Latent class analysis of diagnostic tests for visceral leishmaniasis in Brazil.

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    Machado de Assis, Tália Santana; Rabello, Ana; Werneck, Guilherme Loureiro

    2012-10-01

    To estimate the sensitivities and specificities of different diagnostic tests for visceral leishmaniasis (VL) using latent class analysis (LCA).   This study was performed using data from a prospective study conducted in four Brazilian states from May 2004 to May 2007. Five diagnostic tests for VL were evaluated in 285 VL cases and 119 non-cases: microscopy, indirect fluorescence antibody test (IFAT), enzyme-linked immunosorbent assay using recombinant K39 antigen (rK39-ELISA), direct agglutination test (DAT) and the rK39 rapid test. Microscopy showed sensitivity of 77.0% (CI: 71.5-81.5) and specificity of 99.0% (CI: 94.0-99.7). The IFAT and the DAT showed similar sensitivities, 88.3% (CI: 84.0-92.0) and 88.5% (CI: 84.1-92.0), respectively, but the DAT had a higher specificity (95.4%, CI: 89.2-98.1) than did the IFAT (83.0%, CI: 75.0-88.2). The rK39-ELISA and the rK39 rapid test showed sensitivities of 99.0% (CI: 96.3-99.6) and 94.0% (CI: 90.1-96.3), and specificities of 82.5% (CI: 75.0-88.3) and 100% (CI: 97.0-100.0%), respectively. Considering the lack of an adequate reference standard, LCA proved to be a useful tool in validating diagnostic methods for VL. The DAT and the rK39 rapid test showed better performance. Thus, clinically suspected cases of VL in a Brazilian endemic area could be treated based on the positivity of one of these tests. © 2012 Blackwell Publishing Ltd.

  14. Inference of population structure of Leishmania donovani strains isolated from different Ethiopian visceral leishmaniasis endemic areas.

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    Tesfaye Gelanew

    Full Text Available BACKGROUND: Parasites' evolution in response to parasite-targeted control strategies, such as vaccines and drugs, is known to be influenced by their population genetic structure. The aim of this study was to describe the population structure of Ethiopian strains of Leishmania donovani derived from different areas endemic for visceral leishmaniasis (VL as a prerequisite for the design of effective control strategies against the disease. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-three strains of L. donovani newly isolated from VL cases in the two main Ethiopian foci, in the north Ethiopia (NE and south Ethiopia (SE of the country were investigated by using 14 highly polymorphic microsatellite markers. The microsatellite profiles of 60 previously analysed L. donovani strains from Sudan, Kenya and India were included for comparison. Multilocus microsatellite typing placed strains from SE and Kenya (n = 30 in one population and strains from NE and Sudan (n = 65 in another. These two East African populations corresponded to the areas of distribution of two different sand fly vectors. In NE and Sudan Phlebotomus orientalis has been implicated to transmit the parasites and in SE and Kenya P. martini. The genetic differences between parasites from NE and SE are also congruent with some phenotypic differences. Each of these populations was further divided into two subpopulations. Interestingly, in one of the subpopulations of the population NE we observed predominance of strains isolated from HIV-VL co-infected patients and of strains with putative hybrid genotypes. Furthermore, high inbreeding irreconcilable from strict clonal reproduction was found for strains from SE and Kenya indicating a mixed-mating system. CONCLUSIONS/SIGNIFICANCE: This study identified a hierarchical population structure of L. donovani in East Africa. The existence of two main, genetically and geographically separated, populations could reflect different parasite-vector associations

  15. No evidence for association between SLC11A1 and visceral leishmaniasis in India

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    Fakiola Michaela

    2011-05-01

    Full Text Available Abstract Background SLC11A1 has pleiotropic effects on macrophage function and remains a strong candidate for infectious disease susceptibility. 5' and/or 3' polymorphisms have been associated with tuberculosis, leprosy, and visceral leishmaniasis (VL. Most studies undertaken to date were under-powered, and none has been replicated within a population. Association with tuberculosis has replicated variably across populations. Here we investigate SLC11A1 and VL in India. Methods Nine polymorphisms (rs34448891, rs7573065, rs2276631, rs3731865, rs17221959, rs2279015, rs17235409, rs17235416, rs17229009 that tag linkage disequilibrium blocks across SLC11A1 were genotyped in primary family-based (313 cases; 176 families and replication (941 cases; 992 controls samples. Family- and population-based analyses were performed to look for association between SLC11A1 variants and VL. Quantitative RT/PCR was used to compare SLC11A1 expression in mRNA from paired splenic aspirates taken before and after treatment from 24 VL patients carrying different genotypes at the functional promoter GTn polymorphism (rs34448891. Results No associations were observed between VL and polymorphisms at SLC11A1 that were either robust to correction for multiple testing or replicated across primary and replication samples. No differences in expression of SLC11A1 were observed when comparing pre- and post-treatment samples, or between individuals carrying different genotypes at the GTn repeat. Conclusions This is the first well-powered study of SLC11A1 as a candidate for VL, which we conclude does not have a major role in regulating VL susceptibility in India.

  16. Augmentation of antileishmanial efficacy of miltefosine in combination with tuftsin against experimental visceral leishmaniasis.

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    Shakya, Nishi; Sane, Shraddha A; Haq, Wahajul; Gupta, Suman

    2012-08-01

    Current drugs for the treatment of visceral leishmaniasis are inadequate, and their efficacies are also compromised due to suppression of immune function during the course of infection. Miltefosine is the only promising orally active antileishmanial drug, but due to its long half-life, there is risk of development of resistance. To overcome these problems, efforts are needed to develop combination therapy of miltefosine with effective immunostimulating agents where a decrease of parasitic burden and simultaneous enhancement of adaptive immunity can be achieved. In the present study, we have explored the antileishmanial efficacy of a subcurative dose of miltefosine in combination with free as well as liposomal palmitoyl tuftsin (p-tuftsin) using a Leishmania donovani/BALB/c mouse model. When miltefosine (2.5 mg/kg for 5 days) was given with free p-tuftsin, the inhibitory effect was significantly increased from 49.6% to 66% (P < 0.01), which was further enhanced up to 81% (P < 0.001) when given after liposomal encapsulation of p-tuftsin. Significant enhancement in parasitic inhibition (93%, P < 0.01) was witnessed when animals were co-administered with liposomal p-tuftsin + 5 mg/kg × 5 days dose of miltefosine (72.1%). Enhancement in the production of Th1 cytokines (IL-12, TNF-α, and IFN-γ), reactive oxygen, and nitrogen metabolites was witnessed in the combination group. A remarkable increase in phagocytosis index was also observed indicating overall immunological enhancement to antileishmanial activity of miltefosine by p-tuftsin.

  17. Evaluation of FcγRIIIB-NA1/NA2 Polymorphism in Visceral Leishmaniasis.

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    Abasi, Mohammad; Lotfi, Pegah; Bazmani, Ahad; Matini, Mohamad; Hajilooi, Mehrdad

    2014-04-01

    Several lines of evidence demonstrating that innate and adaptive immunity play important roles in the defense against visceral leishmaniasis (VL). A polymorphism within the FcγRIIIB gene can lead to the expression of three variants of NA1, NA2, and the combined one (NA1/NA2) which alters affinity of IgG to its receptor. The main aim of this study was to evaluate the FcγRIIIB-NA1/NA2 polymorphism in the FcγRIIIB gene of VL patients in comparison to healthy controls. In this cross-sectional study, three groups; 54 seropositive patients with clinical presentation of VL (group 1), 104 seropositive patients without clinical presentation (group 2), and 104 healthy controls (group 3) were evaluated with respect to the FcγRIIIB-NA1/NA2 polymorphism using a PCR-SSP method. The titration of anti-leishmania antibodies was analyzed using an immunoflorescence technique. Our results indicated that polymorphisms within the FcγRIIIB gene (that lead to the expression of the NA1/NA2 isoforms) are significantly associated with VL. The results demonstrated that the genotype heterozygotic for FcγRIIIB-NA1/NA2 expression was significantly increased in VL patients, group 1 when compared to groups 2 and 3. Conversely, there is a decrease in homozygous NA1 and NA2 genotypes in VL patients; however, the overall frequency of NA1 and NA2 alleles appear similar across the three cohorts examined. According to our results, it is likely that the increased frequency of the FcγRIIIB-NA1/NA2 genotype is associated with impaired immune responses against VL and its subsequent clearance from the patient.

  18. 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.

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

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    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

  20. Efficacy of low doses of amphotericin B plus allicin against experimental visceral leishmaniasis.

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    Corral, M Jesús; Serrano, Dolores R; Moreno, Inmaculada; Torrado, J J; Domínguez, Mercedes; Alunda, José M

    2014-12-01

    To evaluate the efficacy of the combination of allicin and amphotericin deoxycholate (AmB) in the chemotherapy of Leishmania infantum infection with the final aim of reducing the dose of AmB in the chemotherapy of visceral leishmaniasis. Hamsters were intraperitoneally (ip) infected with L. infantum (10(7) stationary phase promastigotes). On day 45 post-infection animals were treated ip with AmB (1 or 5 mg/kg/day), allicin (5 mg/kg/day) or a combination of AmB (1 mg/kg/day) + allicin (5 mg/kg/day) for 5 days. Animals were clinically and biopathologically monitored and the antibody response (IgG, IgG1, IgG2) was determined. Parasite burdens were estimated by limiting dilution and AmB biodistribution was determined by HPLC in plasma, kidney, spleen and liver. No clinical signs or liver and kidney alterations were observed. AmB (1 mg/kg/day) did not clear the Leishmania infection and no parasites were detected in two animals treated with 5 mg/kg/day allicin. Combination therapy (5 mg/kg allicin + 1 mg/kg AmB) reduced the L. infantum burden by >95%. Antileishmanial activity of the combination was comparable (P Allicin alone (5 mg/kg/day for 5 days) significantly reduced the Leishmania burden in spleen and liver of infected hamsters. Co-administration of allicin (5 mg/kg/day for 5 days) and AmB (1 mg/kg/day for 5 days) showed a partial additive effect on the reduction of leishmanial burden in both target organs. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Canine leishmaniosis and its relationship to human visceral leishmaniasis in Eastern Uzbekistan.

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    Kovalenko, Dmitriy A; Razakov, Shavkat A; Ponirovsky, Evgeny N; Warburg, Alon; Nasyrova, Rokhat M; Ponomareva, Valentina I; Fatullaeva, Aziza A; Nasereddin, Abdelmajeed; Klement, Eyal; Alam, Mohammad Z; Schnur, Lionel F; Jaffe, Charles L; Schönian, Gabriele; Baneth, Gad

    2011-04-13

    The Namangan Region in the Pap District, located in Eastern Uzbekistan is the main focus of visceral leishmaniasis (VL) in Uzbekistan. In total, 28 cases of human VL were registered during 2006-2008 in this region. A study on the epidemiology of VL in this area was carried out in 2007-2008 in the villages of Chodak, Oltinkan, Gulistan and Chorkesar located at elevations of 900-1200 above sea level. A total of 162 dogs were tested for Leishmania infection. Blood was drawn for serology and PCR. When clinical signs of the disease were present, aspirates from lymph nodes and the spleen were taken. Forty-two dogs (25.9%) had clinical signs suggestive of VL and 51 (31.5%) were sero-positive. ITS-1 PCR was performed for 135 dogs using blood and tissue samples and 40 (29.6%) of them were PCR-positive. Leishmanial parasites were cultured from lymph node or spleen aspirates from 10 dogs.Eight Leishmania strains isolated from dogs were typed by multi-locus microsatellite typing (MLMT) and by multilocus enzyme electrophoretic analysis (MLEE), using a 15 enzyme system. These analyses revealed that the strains belong to the most common zymodeme of L. infantum, i.e., MON-1, and form a unique group when compared to MON-1 strains from other geographical regions. The data obtained through this study confirm the existence of an active focus of VL in the Namangan region of Uzbekistan. The fact that L. infantum was the causative agent of canine infection with typical clinical signs, and also of human infection affecting only infants, suggests that a zoonotic form of VL similar in epidemiology to Mediterranean VL is present in Uzbekistan.

  2. [Human and canine visceral leishmaniasis in the Papsky District, Namangan Region, Uzbekistan: seroepidemiological and seroepizootological surveys].

    Science.gov (United States)

    Kovalenko, D A; Nasyrova, R M; Ponomareva, V I; Fatullaeva, A A; Razakov, Sh A; Ponirovskiĭ, E N; Strelkova, M V; Zhirenkina, E N; Morozov, E N; Dzhaf, Ch; Banet, G; Shnur, L; Varburg, A; Shonian, G

    2011-01-01

    In 2007 - 2008, four (Chodak, Oltinkan, Gulistan, and Chorkesar) of 9 population aggregates in the Papsky District, Namangan Region, Uzbekistan, where visceral leishmaniasis (VL) cases had been registered in the last years were selected to make seroepidemiological and seroepizootological surveys within the international project funded by INTAS grant 05-100006-8043. The surveys of the populations were conducted visiting their homesteads. These additionally included children's and health care facilities where all children aged less than 14 years were examined. On examining the children, their peripheral blood (approximately 0.1 ml) was taken on filter paper for serological assays. Canine blood was sampled from the vein. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect antibodies to VL pathogens. A total of 521 children were examined for two years, by applying ELISA. Five hundred and fourteen blood samples from children younger than 14 years, 162 dogs, 4 foxes, and 1 cat were tested. Testing 514 children's blood samples for VL pathogen antigen ascertained that in the 4 population aggregates there was an average of 10% VL-seropositive children, including those who were ill with VL at the moment of the examination and had been ill. The highest number of VL-seropositive samples (14.9%) was found in the settlement of Chodak. VL pathogen antibodies were detected in 26 (61.9%) of 42 dogs with the clinical signs of VL. VL-positive tests were found in 26 (21.6%) of 120 apparently healthy dogs. The samples from 4 foxes and 1 cat were negative. Immunological findings indicated that 0-3-year-old children were a group that is most susceptible to VL in the study focus of this disease. The high proportion of dogs with VL may account for the rise in infant morbidity and suggests the epizootic strain in the focus of VL in the Papsky District.

  3. Risk factors for visceral leishmaniasis in India: further evidence on the role of domestic animals.

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    Singh, S P; Hasker, E; Picado, A; Gidwani, K; Malaviya, P; Singh, R P; Boelaert, M; Sundar, S

    2010-07-01

    Studies investigating risk factors for visceral leishmaniasis (VL) on the Indian Subcontinent have shown contradictory results related to the role of domestic animals. In some studies having animals in or around the house was a risk factor, in others it was protective. We investigated the specific hypothesis that keeping domestic animals inside the house at night is a risk factor for VL. Individually matched case-control study. All patients with VL diagnosed in the study area in Bihar, India between March 1st, 2007 and December 1st, 2008 were eligible. For each case, we selected two random controls, with no history of previous VL; matched on sex, age group and neighbourhood. Patients and controls were subjected to a structured interview on the main exposure of interest and potential confounders; a conditional logistic regression model was used to analyse the data. We enrolled 141 patients and 282 controls. We found no significant associations between VL and keeping domestic animals inside the house (OR of 0.88 for bovines and 1.00 for 'any animal') or ownership of domestic animals (OR of 0.97 for bovines and 1.02 for 'any animal'). VL was associated with housing conditions. Living in a thatched house (OR 2.60, 95% CI 1.50-4.48) or in a house with damp floors (OR 2.60, 95% CI 1.25-5.41) were risk factors, independently from socio economic status. Keeping animals inside the house is not a risk factor for VL in Bihar, India. Improving housing conditions for the poor has the potential to reduce VL incidence.

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

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    Wang Jun-Yun

    2012-02-01

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

  5. sCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis.

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    Ricardo Luís Louzada Silva

    2017-03-01

    Full Text Available CD163, receptor for the haptoglobin-hemoglobin complex, is expressed on monocytes/macrophages and neutrophils. A soluble form of CD163 (sCD163 has been associated with the M2 macrophage phenotype, and M2 macrophages have been shown to down-modulate inflammatory responses. In particular, previous studies have shown that M2 is closely associated with the most severe clinical presentation of leprosy (i.e. lepromatous leprosy (LL, as well as tuberculosis. We hypothesized that sCD163 correlates with severity of diseases caused by intracellular pathogens.To assess this hypothesis, sCD163 levels were measured in the serum of leprosy and visceral leishmaniasis (VL patients stratified by severity of the clinical presentation. sCD163 levels were significantly higher in patients with these diseases than those observed in healthy control individuals. Further analyses on infection and disease status of leprosy and VL patients revealed a clear association of sCD163 levels with clinical parameters of disease severity. In vitro culture assays revealed that Leishmania infection induced CD163 expression on the surface of both monocyte/macrophages and neutrophils, suggesting these cells as possible sources of sCD163. FACS analyses shows that the cells expressing CD163 produces both TNF-α and IL-4.Taken together, our results reveal sCD163 as a potential biomarker of severity of diseases caused by intracellular pathogens M. leprae and Leishmania spp. and have a modulatory role, with a mix of an inflammatory property induced by TNF-α release, but that potentially induces an anti-inflammatory T cell response, related to IL-4 release.

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

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    Bhattacharyya, Tapan; Bowes, Duncan E; El-Safi, Sayda; Sundar, Shyam; Falconar, Andrew K; Singh, Om Prakash; Kumar, Rajiv; Ahmed, Osman; Boelaert, Marleen; Miles, Michael A

    2014-02-01

    Visceral leishmaniasis (VL), a widely distributed systemic disease caused by infection with the Leishmania donovani complex (L. donovani and L. infantum), is almost always fatal if symptomatic and untreated. A rapid point-of-care diagnostic test for anti-Leishmania antibodies, the rK39-immunochromatographic test (rK39-ICT), has high sensitivity and specificity in South Asia but is less sensitive in East Africa. One of the underlying reasons may be continent-specific molecular diversity in the rK39 antigen within the L. donovani complex. However, a second reason may be differences in specific IgG anti-Leishmania levels in patients from different geographical regions, either due to variable antigenicity or immunological response. We determined IgG titres of Indian and Sudanese VL patients against whole cell lysates of Indian and Sudanese L. donovani strains. Indian VL patients had significantly higher IgG titres against both L. donovani strains compared to Sudanese VL patients (pIgG titres occurred in children (IgG responses was between male Indian and Sudanese VL patients of ≥ 16 years old (mean 1/log10t50: 4.15 versus 1.99 = 144-fold (pIgG responses among VL patients in Sudan were significantly lower than in India; this may be due to chronic malnutrition with Zn(2+) deficiency, or variable antigenicity and capacity to generate IgG responses to Leishmania antigens. Such differential anti-Leishmania IgG levels may contribute to lower sensitivity of the rK39-ICT in East Africa.

  7. Human visceral leishmaniasis in kermanshah province, Western iran, during 2011-2012.

    Science.gov (United States)

    Hamzavi, Y; Hamzeh, B; Mohebali, M; Akhoundi, B; Ajhang, Kh; Khademi, N; Ghadiri, K; Bashiri, H; Pajhouhan, M

    2012-01-01

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

  8. Changes in the epidemiology of visceral leishmaniasis in Brazil from 2001 to 2014

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    Lisiane Lappe dos Reis

    Full Text Available Abstract INTRODUCTION Visceral leishmaniasis (VL is a neglected disease, with territorial expansion and regional differences in Brazil that require explanation. This study aimed to describe changes in the epidemiology of VL in Brazil from 2001 to 2014. METHODS The incidence rates, sociodemographic and clinical data, and case evolution were subgrouped from 2001 to 2006 and from 2007 to 2014 and presented descriptively. Spatial distribution of disease incidence rates and changes in the spatial and temporal pattern were examined. RESULTS: In total, 47,859 VL cases were reported in Brazil between 2001 and 2014, with predominance in the Northeast macroregion (55%, though the incidence rate in this region declined between the two study periods. The State of Tocantins had the highest crude rate (26.2/100,000 inhabitants, which was responsible for VL increasing in the North macroregion. VL predominated in the urban zone (70%, in children under 4 years (34%; however, an increase in the incidence of VL in adults older than 40 years was identified, with 12.3% and 31% in the first and second period, respectively. The mapping of crude rates and autochthonous canine cases showed territorial expansion. The temporal distribution of VL was consistent in Brazil in general, with no pattern observed, but regional differences were found. CONCLUSIONS: The incidence of VL is increasing in Brazil. In addition to the State of Tocantins, which had the highest rate, new outbreaks of VL have occurred in the South macroregion of Brazil with small decreases identified in the incidence rate in the Northeast.

  9. Immunogenicity in dogs and protection against visceral leishmaniasis induced by a 14 kDa Leishmania infantum recombinant polypeptide

    OpenAIRE

    Claudia Abeijon; Nada Daifalla; Greice Krautz-Peterson; Stefano Pizzirani; Gillian Beamer; Neuza M. Frazatti-Gallina; Isaias Raw; Antonio Campos-Neto

    2016-01-01

    In areas were human visceral leishmaniasis (VL) is endemic, the domestic dog is the main parasite reservoir in the infectious cycle of Leishmania infantum. Development of prophylactic strategies to lower the parasite burden in dogs would reduce sand fly transmission thus lowering the incidence of zoonotic VL. Here we demonstrate that vaccination of dogs with a recombinant 14 kDa polypeptide of L. infantum nuclear transport factor 2 (Li-ntf2) mixed with adjuvant BpMPLA-SE resulted in the produ...

  10. 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.

  11. 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.

  12. Isolation of Leishmania infantum, zymodeme MON-1 from canine and human visceral leishmaniasis on Margarita Island, Venezuela.

    Science.gov (United States)

    Zerpa, O; Pratlong, F; Ulrich, M; Convit, J

    2001-10-01

    An increase in the incidence of human visceral leishmaniasis (HVL) has been detected in recent years on Margarita Island, located off the NE coast of Venezuela. Recent studies have revealed reactivity to rK39 antigen (Leishmania chagasi) in 20% of 541 sera from domestic dogs in endemic communities; PCR reactions were positive using primers for the L. donovani complex. Here we report that isolates from human and canine infection, identified by isoenzyme analysis, correspond to L. infantum, zymodeme MON-1. This appears to be the first isolation and identification of an isolate from HVL on Margarita Island and demonstrates the presence of this zymodeme in the canine population.

  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. Leishmaniasis

    Science.gov (United States)

    ... Award Resident Research Paper Award Surgery in the Outback CME CME Attestation CME Disclosure CME Objectives CME ... leishmaniasis are in India, Bangladesh, Nepal, Sudan, and Brazil. Leishmaniasis is found in some parts of the ...

  15. Autochthonous visceral leishmaniasis in Brasília, Federal District, Brazil Leishmaniose visceral autóctone em Brasília, Distrito Federal, Brasil

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    César Omar Carranza-Tamayo

    2010-08-01

    Full Text Available INTRODUCTION: Visceral leishmaniasis is a public health threat in Brazil considering the high lethality rates and increasing geographical dispersion to large urban conglomerates over the past 25 years. This study aimed to confirm suspected autochthonous cases of visceral leishmaniasis reported from 2005 to 2009 among individuals living in Brasilia, Federal District. METHODS: A retrospective review of the surveillance data obtained on a regular basis and clinical records of the reported cases were performed in 2009. RESULTS: Data from entomological and canine surveys revealed the presence of both Lutzomyia longipalpis and positive serology for Leishmania in dogs within 19 of the 21 neighborhoods where human cases occurred since 2005. The review of surveillance data and medical records, together with the entomological and canine survey data, permitted confirmation of 21 autochthonous human cases in the Federal District. The disease predominantly affected children (12/21 and those from the Sobradinho region (16/21; the typical presentation of fever, hepatosplenomegaly and pancytopenia was observed in 67% of cases. Three deaths occurred during the study period. Leishmania (Leishmania chagasi was successfully isolated from one human case and twelve canine cases. CONCLUSIONS: Visceral leishmaniasis should be considered endemic in Brasilia based on the documented epidemiological behavior herein described and the confirmed autochthony of human cases.INTRODUÇÃO: A leishmaniose visceral é uma ameaça para a saúde pública no Brasil, considerando a elevada taxa de letalidade e a sua dispersão geográfica para grandes conglomerados urbanos durante os últimos 25 anos. Este trabalho teve como objetivo confirmar a suspeita de autoctonia de casos de leishmaniose visceral notificados de 2005 até 2009 em moradores de Brasília, Distrito Federal. MÉTODOS: Foi realizado em 2009 um estudo retrospectivo dos dados da vigilância obtidos na rotina e dos

  16. Foco emergente de leishmaniose visceral em Mato Grosso do Sul Emergent outbreak of visceral leishmaniasis in Mato Grosso do Sul State

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    Ana Lúcia Lyrio de Oliveira

    2006-10-01

    Full Text Available Este trabalho, realizado a partir de outubro de 2000 até janeiro de 2003, descreve as características clínico-epidemiológicas da leishmaniose visceral em Três Lagoas, Mato Grosso do Sul. Foram confirmados 149 casos da doença, com predominância do sexo masculino (71,1%. A faixa etária mais acometida foi de 0 a 4 anos (42%. Quanto ao quadro clínico, estiveram presente febre (97,3%, esplenomegalia (85,9% e anemia (75,8%. Em 32 (21,5% pacientes ocorreu infecção associada, predominando a pneumonia. Sobre as alterações laboratoriais observou-se mediana de hemoglobina de 8mg/dl e de leucócitos de 3.100 cel/mm³. O esfregaço de medula foi positivo em 90,6%. Dos 97,9% de pacientes tratados, 78,2% utilizaram antimoniato pentavalente. Ocorreram 8% de óbitos, metade deles portadores de infecção associada. O conjunto destes dados sugere mudanças no padrão fisiográfico de ocorrência da leishmaniose visceral na localidade, com expansão e urbanização da doença, necessitando atenção para o diagnóstico e tratamento precoces.This study, realized from October 2000 to January 2003 describes the clinical epidemiological characteristics of visceral leishmaniasis in Três Lagoas, Mato Grosso do Sul State, Brazil. A total of 149 cases were confirmed, with a predominance of the male gender (71.1%. The principal age group was aged 0 to 4 years old (42%. The clinical picture included fever (97.3%, esplenomegaly (85.9% and anemia (75.8%. Associated infections were seen in 32 patients (21.5%, pneumonia being most common. Changes registered in the laboratory included a median hemoglobin level of 8mg/dl and 3,100 leucocytes/mm³. Bone marrow smears were positive in 90.6% of patients. Of the 97.9% patients treated, 78.2% used pentavalent antimony. Mortalities occurred in 8% of cases, half of these with associated infection. Taken together, these data suggest changes in the physiographical occurrence of visceral leishmaniasis in this locality, with

  17. 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.

  18. Diagnosis of Mediterranean visceral leishmaniasis by detection of Leishmania-related antigen in urine and oral fluid samples.

    Science.gov (United States)

    Ben-Abid, Meriem; Galaï, Yousr; Habboul, Zakia; Ben-Abdelaziz, Rim; Ben-Sghaier, Ines; Aoun, Karim; Bouratbine, Aïda

    2017-03-01

    Implementation of simple diagnostic tests using non-invasive collection of biological specimens is of great importance in the diagnosis of pediatric visceral leishmaniasis caused by Leishmania infantum. Latex agglutination kit (KAtex®) is widely used in the diagnosis mainly in L. donovani endemic areas. However its utilization in L. infantum endemic regions remains limited and its use on noninvasive biological specimen apart urine was not reported. In this study, KAtex® kit was used to detect Leishmania-related antigen in urine and oral fluid of 35 L. infantum visceral leishmaniasis cases and 62 controls including non-infectious disease and infectious disease controls (34 and 28 respectively). Sensitivity and specificity of urine based KAtex® were 51.4% and 98.3% respectively, whereas, sensitivity and specificity of oral-fluid based KAtex® were 80% and 88.3% respectively. Although, sensitivity of oral-fluid KAtex® was high, its specificity varied significantly according to the presence or the absence of an infectious disease (71.4% versus 97%, p=0.01). Copyright © 2016 Elsevier B.V. All rights reserved.

  19. 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. © 2013 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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.

  1. Leishmaniose visceral canina em Maricá, Estado do Rio de Janeiro: relato do primeiro caso autóctone Canine visceral leishmaniasis in Maricá, State of Rio de Janeiro: first report of an autochthonous case

    OpenAIRE

    Cíntia Cristiane de Paula; Fabiano Borges Figueiredo; Rodrigo Caldas Menezes; Eliame Mouta-Confort; Alessandra Bogio; Maria de Fátima Madeira

    2009-01-01

    Leishmaniose visceral é uma zoonose de importância em Saúde Pública, onde os cães representam um dos maiores problemas. Este trabalho visa relatar o primeiro caso autóctone da leishmaniose visceral canina no município de Maricá, fornecendo elementos relacionados à distribuição geográfica de Leishmania (Leishmania) chagasi no Estado do Rio de Janeiro.Visceral leishmaniasis is a zoonosis of public health importance, and dogs represent one of the main problems. This paper describes the first aut...

  2. A expansão da epidemia da leishmaniose visceral no Estado de Mato Grosso, 1998-2005 The spread of the visceral leishmaniasis epidemic in the State of Mato Grosso, 1998-2005

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    Gustavo Leandro da Cruz Mestre

    2007-02-01

    Full Text Available Uma epidemia de leishmaniose visceral teve início em 1998 na Região Metropolitana de Cuiabá, capital de Mato Grosso, atingindo hoje 34 (24,1% dos 141 municípios do estado. Entre janeiro de 1998 e dezembro de 2005, foram notificados 138 casos autóctones, predominando o sexo masculino (58%, crianças (51,5% de 0-9 anos e residentes (66,7% de áreas urbanas. A leishmaniose visceral canina foi identificada em 41 municípios, com soropositividade de 9% em 40.000 cães examinados. Lutzomyia longipalpis e/ou Lutzomyia cruzi foram capturadas em 14 dos 18 municípios que registraram simultaneamente leishmaniose visceral humana e canina. Os resultados indicam que a transmissão da leishmaniose visceral dissemina-se para o interior do estado, acompanhando o fluxo migratório e o processo de ocupação urbana desordenada das cidades. A presença isolada de Lutzomyia cruzi em municípios com alta incidência de casos humanos e caninos de leishmaniose visceral sugere possível participação desta espécie na cadeia de transmissão dessa parasitose em Mato Grosso.An epidemic of visceral leishmaniasis began in 1998, in the Metropolitan Region of Cuiabá, the capital of the State of Mato Grosso, Brazil. Today, it has reached 34 (24.1% of the 141 municipalities in the state. Between January 1998 and December 2005, 138 autochthonous cases were notified, mainly in males (58%, children aged 0-9 years (51.5% and inhabitants of urban areas (66.7%. Canine visceral leishmaniasis has been detected in 41 municipalities, with positive serum in 9% of the 40,000 dogs examined. Lutzomyia longipalpis and/or Lutzomyia cruzi were captured in 14 out of the 18 municipalities that simultaneously recorded both human and canine visceral leishmaniasis. These findings indicate that visceral leishmaniasis transmission has become disseminated throughout the state, following migratory flows and the process of disorderly occupation of urban areas. The presence of Lutzomyia cruzi

  3. 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

    2016-01-01

    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. PMID:27162266

  4. A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH.

    Science.gov (United States)

    Osman, Mohamed; Mistry, Anoop; Keding, Ada; Gabe, Rhian; Cook, Elizabeth; Forrester, Sarah; Wiggins, Rebecca; Di Marco, Stefania; Colloca, Stefano; Siani, Loredana; Cortese, Riccardo; Smith, Deborah F; Aebischer, Toni; Kaye, Paul M; Lacey, Charles J

    2017-05-01

    Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. This

  5. 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.

  6. Varied spectrum of clinical presentation and mortality in a prospective registry of visceral leishmaniasis in a low endemicity area of Northern Italy.

    Science.gov (United States)

    Cenderello, Giovanni; Pasa, Ambra; Dusi, Andrea; Dentone, Chiara; Toscanini, Federica; Bobbio, Nicoletta; Bondi, Elisabetta; Del Bono, Valerio; Izzo, Manuela; Riccio, Giovanni; Anselmo, Marco; Giacchino, Raffaella; Marazzi, Maria Grazia; Pagano, Gabriella; Cassola, Giovanni; Viscoli, Claudio; Ferrea, Giuseppe; De Maria, Andrea

    2013-05-30

    Visceral Leishmaniasis (VL) is endemic in 88 countries, in areas of relatively low incidence with a relevant proportion of immune suppressed patients clinical presentation, diagnosis and management may present difficulties and pitfalls. Demographic data, clinical, laboratory features and therapeutic findings were recorded in patients identified by a regional VL disease registry from January 2007 to December 2010. A total of 55 patients (36 adults mean age 48.7 years, 19 children median age 37.5 months) were observed presenting with 65 episodes. All childen were immunocompetent, whereas adults affected by VL included both immunocompetent (n°17) and immunesuppressed (n°19) patients. The clinical presentation was homogeneous in children with predominance of fever and hepato-splenomegaly. A wider spectrum of clinical presentations was observed in immunocompromised adults. Bone marrow detection of intracellular parasites (Giemsa staining) and serology (IFAT) were the most frequently used diagnostic tools. In addition, detection of urinary antigen was used in adult patients with good specificity (90%). Liposomal amphotericin B was the most frequently prescribed first line drug (98.2% of cases) with 100% clinical cure. VL relapses (n°10) represented a crucial finding: they occurred only in adult patients, mainly in immunocompromised patients (40% of HIV, 22% of non-HIV immunocompromised patients, 5,9% of immunocompetent patients). Furthermore, three deaths with VL were reported, all occurring in relapsing immunocompromised patients accounting for a still high overall mortality in this group (15.8%). The wide spectrum of clinical presentation in immunesuppresed patients and high recurrence rates still represent a clinical challenge accounting for high mortality. Early clinical identification and satisfactory treatment performance with liposomal amphotericin B are confirmed in areas with low-level endemicity and good clinical standards. VL needs continuing attention in

  7. 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.

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

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    Anaiá P Sevá

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

  9. Visceral Leishmaniasis in Iran: Review of the Epidemiological and Clinical Features

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    Mehdi Mohebali

    2013-09-01

    Full Text Available Visceral leishmaniasis (VL is a life-threatening vector-borne parasitic dis­ease is distributed in some parts of the new world and old world. The disease is endemic in different parts of Iran. This review article has been focused on major topics of epidemio­logical aspects and clinical features of VL in Iran for the period of 2002 through 2012. For the detection of VL in humans as well as animal reservoir hosts, anti-Leishmania antibodies were detected using direct agglutination test (DAT as a validated serological test. Parasitological examinations were performed on suspected VL patients as well as canines and rodents. Different molecular methods were used for identification of species and genotype/ or strain of Leishmania spp. isolated from infected humans, animal reser­voir hosts and vectors. Altogether, 1698 out of 36081 (4.7% human serum samples collected from 5 distinct geographical zones showed anti-Leishmania antibodies at ti­ters≥1:3200 using DAT. The majority of VL cases in the endemic areas were found among children up to 12 years old. Almost 75% of DAT-positive cases (≥1:3200 in en­demic areas showed clinical signs and symptoms. Predominant signs and symptoms in 217 hospitalized patients with DAT positive (≥1:3200 results included paleness (99.5%, fever (96.9%, splenomegaly (91.5%, hepatomegaly (53.6% and lymphadenopathy (21.1%. Integrated VL surveillance system in primary care using DAT, could decrease mortality and morbidity of the disease in the VL endemic areas of the northwestern Iran. Out of 7204 serum samples collected from domestic dogs in various geographical loca­tions of Iran, 879 (12.2% were DAT sero-positive at titers≥1:320. L. infantum as the prin­cipal causative agent of the disease was isolated from infected humans, domestic and wild canines and rodents. The principal animal reservoir hosts of the infection are domestic and wild canines. Ph. kandelakii, Ph. perfiliewi transcaucasicus, Ph. tobbi in

  10. Evaluating the accuracy of molecular diagnostic testing for canine visceral leishmaniasis using latent class analysis.

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    Manuela da Silva Solcà

    Full Text Available Host tissues affected by Leishmania infantum have differing degrees of parasitism. Previously, the use of different biological tissues to detect L. infantum DNA in dogs has provided variable results. The present study was conducted to evaluate the accuracy of molecular diagnostic testing (qPCR in dogs from an endemic area for canine visceral leishmaniasis (CVL by determining which tissue type provided the highest rate of parasite DNA detection. Fifty-one symptomatic dogs were tested for CVL using serological, parasitological and molecular methods. Latent class analysis (LCA was performed for accuracy evaluation of these methods. qPCR detected parasite DNA in 100% of these animals from at least one of the following tissues: splenic and bone marrow aspirates, lymph node and skin fragments, blood and conjunctival swabs. Using latent variable as gold standard, the qPCR achieved a sensitivity of 95.8% (CI 90.4-100 in splenic aspirate; 79.2% (CI 68-90.3 in lymph nodes; 77.3% (CI 64.5-90.1 in skin; 75% (CI 63.1-86.9 in blood; 50% (CI 30-70 in bone marrow; 37.5% (CI 24.2-50.8 in left-eye; and 29.2% (CI 16.7-41.6 in right-eye conjunctival swabs. The accuracy of qPCR using splenic aspirates was further evaluated in a random larger sample (n = 800, collected from dogs during a prevalence study. The specificity achieved by qPCR was 76.7% (CI 73.7-79.6 for splenic aspirates obtained from the greater sample. The sensitivity accomplished by this technique was 95% (CI 93.5-96.5 that was higher than those obtained for the other diagnostic tests and was similar to that observed in the smaller sampling study. This confirms that the splenic aspirate is the most effective type of tissue for detecting L. infantum infection. Additionally, we demonstrated that LCA could be used to generate a suitable gold standard for comparative CVL testing.

  11. [An adult case of visceral leishmaniasis in a province of Black-Sea region, Turkey].

    Science.gov (United States)

    Oztoprak, Nefise; Aydemir, Hande; Pişkin, Nihal; Seremet Keskin, Ayşegül; Araslı, Mehmet; Gökmen, Ayla; Celebi, Güven; Külekçi Uğur, Aslıhan; Taylan Özkan, Ayşegül

    2010-10-01

    Visceral leishmaniasis (VL) which is a chronic disease caused by the protozoon, Leishmania, occurs widely worldwide and it is widespread in most of the countries in the Mediterranean basin. The infection which is transmitted by a sandfly (Phlebotomus) vector, has a prolonged incubation period and insidious onset. VL generally affects children and may be fatal if not treated. In this report, a 31 years old male patient, who was the first adult VL case from Zonguldak (a province located at western Black-Sea region of Turkey) was presented. He was admitted to the hospital with two-months history of fever, chills, sweating and weight loss. There was no history of travel outside the city nor insect bites, however, he indicated that there would be unnoticed sandfly bites since sandflies were very common in the coal mines he worked. His physical examination revealed body temperatue of 39.2°C and hepatosplenomegaly, while laboratory findings yielded anemia, leucopenia, hypoalbuminemia and hypergamaglobulinemia. Erythrocyte sedimentation rate was 62 mm/h, C-reactive protein was 113 mg/L and liver transaminases were 2 to 5 folds higher than the reference values. The only pathological finding was hepatosplenomegaly in the abdominal ultrasound and computerized tomography. He was further examined to rule out infections with similar signs and symptoms, connective tissue diseases and malignancies and all were found negative. Hypercellular bone marrow were detected in the aspiration material. Bone marrow smears, bone marrow samples inoculated in NNN medium and serum samples of the patient were sent to the reference parasitology laboratory of Refik Saydam National Public Health Agency for evaluation in terms of VL. The diagnosis was confirmed by the detection of Leishmania IgG titer as 1/512 with in-house indirect immunofluorescence antibody test, by positivite rK39 Dipstick (InBios, USA) test and by the observation of Leishmania amastigote forms in the bone marrow smears. Bone

  12. 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.

  13. 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

  14. A clinical severity scoring system for visceral leishmaniasis in immunocompetent patients in South Sudan.

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    Suzette S Kämink

    2017-10-01

    Full Text Available South Sudan is one of the most endemic countries for visceral leishmaniasis (VL, and is frequently affected by large epidemics. In resource-limited settings, clinicians require a simple clinical tool to identify VL patients who are at increased risk of dying, and who need specialised treatment with liposomal amphotericin B and other supportive care. The aim of this study was to develop and validate a clinical severity scoring system based on risk factors for death in VL patients in South Sudan.A retrospective analysis was conducted of data from a cohort of 6,633 VL patients who were treated in the Médecins Sans Frontières (MSF hospital in Lankien between July 2013 and June 2015. Risk factors for death during treatment were identified using multivariable logistic regression models, and the regression coefficients were used to develop a severity scoring system. Sensitivity and specificity of score cut-offs were assessed by receiver operating characteristic (ROC analysis.In multivariable models, risk factors for death in adult VL patients were: anaemia (odds ratio (OR 4.46 (95% CI 1.58-12.6 for Hb <6g/dL compared with ≥9g/dL, nutritional status (OR 4.84 (2.09-11.2 for BMI <13 kg/m2 compared with ≥16 kg/m2, weakness (OR 4.20 (1.82-9.73 for collapsed compared with normal weakness, jaundice (OR 3.41 (1.17-9.95, and oedema/ascites (OR 4.86 (1.67-14.1. For children and adolescents the risk factors were: age (OR 10.7 (6.3-18.3 for age <2 years compared with 6-18 years, anaemia (OR 7.76 (4.15-14.5 for Hb <6g/dL compared with ≥9g/dL, weakness (OR 3.13 (22.8-105.2 for collapsed compared with normal weakness, and jaundice (OR 12.8 (4.06-40.2. Severity scoring predictive ability was 74.4% in adults and 83.4% in children and adolescents.Our evidenced-based severity scoring system demonstrated sufficient predictive ability to be operationalised as a clinical tool for rational allocation of treatment to VL patients at MSF centres in South Sudan.

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

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    Anaiá da Paixão Sevá

    2017-02-01

    Full Text Available 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

  16. 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....

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

    NARCIS (Netherlands)

    Basiye, Frank L.; Mbuchi, Margaret; Magiri, Charles; Kirigi, George; Deborggraeve, Stijn; Schoone, Gerard J.; Saad, Alfarazdeg A.; El-Safi, Sayda; Matovu, Enock; Wasunna, Monique K.

    2010-01-01

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

  18. Survey of Wild and Domestic Mammals for Infection with Leishmania infantum following an Outbreak of Desert Zoonotic Visceral Leishmaniasis in Jiashi, People's Republic of China.

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    Chun-Hua Gao

    Full Text Available In 2008 and 2009, an outbreak of desert-subtype zoonotic visceral leishmaniasis occurred in Jiashi county, Xinjiang, China. So far, no animal reservoir has been identified for this type of visceral leishmaniasis. Therefore, we surveyed the most common mammals (wild and domestic for Leishmania infections during the outbreak in 2008 and 2009 in order to identify the source of the visceral leishmaniasis in this region. Spleen, liver, bone marrow and blood samples collected from 86 wood mice (Apodemus sylvaticus, 61midday jirds (Meriones meridianus and 27 Yarkand hares (Lepus yarkandensis were tested for the presence of Leishmania by microscopy, culture and PCR. All of the animals were found to be negative for Leishmania infections; On the other hand, Leishmania DNA was detected in blood samples collected from livestock reared in the outbreak area: 30.36% (17/56 of sheep, 21.57% (11/51 of goats, 17.78% (8/45 of cattle, and 21.62 (8/37 of donkeys were positive for Leishmania DNA by PCR. The amplified kDNA sequences from the livestock samples matched Leishmania DNA sequences isolated from patients with visceral leishmaniasis in the study area. We suggest that these domestic mammals are a possible reservoir host for Leishmania infantum in the outbreak area.

  19. Vaccine candidates for leishmaniasis: a review.

    Science.gov (United States)

    Nagill, Rajeev; Kaur, Sukhbir

    2011-10-01

    Leishmaniasis is a diverse group of clinical syndromes caused by protozoan parasites of the genus Leishmania. The clinical manifestation of the disease varies from self-limiting cutaneous lesions to progressive visceral disease. It is estimated that 350 million people are at risk in 88 countries, with a global incidence of 1-1.5 million cases of cutaneous and 500,000 cases of visceral leishmaniasis. The key control measures mainly rely on early case detection and chemotherapy which has been hampered by the toxicity of drugs, side-effects and by the emergence of drug resistance in parasites. Control of reservoir host and vector is difficult due to operational difficulties and frequent relapses in the host. Therefore, the development of effective and affordable vaccine against leishmaniasis is highly desirable. Although considerable progress has been made over the last decade in understanding immune mechanisms underlying potential candidate antigens, including killed, live attenuated parasites, crude parasites, pure or recombinant Leishmania proteins or DNA encoding leishmanial proteins, as well as immunomodulators from sand fly saliva, very few candidate vaccines have progressed beyond the experimental stage. As such there is no vaccine against any form of human leishmaniasis. In recent years, however, much interest has been stimulated towards vaccination against leishmaniasis focused mainly on cutaneous leishmaniasis with fewer attempts against visceral leishmaniasis. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Genetic typing reveals monomorphism between antimony sensitive and resistant Leishmania donovani isolates from visceral leishmaniasis or post kala-azar dermal leishmaniasis cases in India.

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    Subba Raju, B V; Gurumurthy, Srividya; Kuhls, Katrin; Bhandari, Vasundhra; Schnonian, Gabriele; Salotra, Poonam

    2012-10-01

    Resistance to pentavalent antimonials has emerged as a major hurdle to the treatment and control of visceral leishmaniasis (VL), also known as kala-azar (KA), caused by Leishmania donovani. In India, over 60% of KA patients are unresponsive to the first-line drug sodium antimony gluconate (SAG). Resistance determinants in laboratory strains are partly known; however, the mechanism operating in field isolates is not well understood. In this study, we attempted to analyze the genetic polymorphism between SAG sensitive and resistant parasites using a total of 52 L. donovani isolates obtained either from bone marrow of VL patients or from skin lesions of post kala-azar dermal leishmaniasis (PKDL) patients that constitute an important reservoir of parasite. The clinical isolates were analyzed in comparison with L. donovani parasites from reference strains belonging to distinct geographical locations, at internal transcribed spacer 1 region; coding region of gp63 and nine microsatellite repeat regions. Our results demonstrated that both SAG resistant (n = 26) and sensitive (n = 19) Indian isolates, whether causing VL or PKDL, were monomorphic at all the genetic loci tested, unlike the L. donovani in East African or Leishmania infantum in Mediterranean countries where intraspecies variations exist at these loci. Further, the Indian isolates were found closest to the Kenyan isolates of L. donovani on the basis of fragment analysis of microsatellite markers.

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

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    G.M. de C. Viana

    1994-08-01

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

  2. 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...

  3. Leishmania infection and blood food sources of phlebotomines in an area of Brazil endemic for visceral and tegumentary leishmaniasis

    Science.gov (United States)

    Guimarães-e-Silva, Antônia Suely; Silva, Soraia de Oliveira; Ribeiro da Silva, Rosa Cristina; Pinheiro, Valéria Cristina Soares; Rebêlo, José Manuel Macário; Melo, Maria Norma

    2017-01-01

    The aims of the study were to determine the blood feeding preferences of sandflies and to identify species of Leishmania that infected phlebotomines in Caxias, Maranhão, Brazil, an area that is highly endemic for leishmaniasis. Sandflies were captured in light traps located in the peridomiciliary environments of randomly selected houses in urban and rural settings between 1800 and 0600 hours on new moon days between March 2013 and February 2015. DNA extracts from 982 engorged female sandflies were submitted to fragment length polymorphism analysis to identify infecting species of Leishmania, and blood sources were identified for 778 of these specimens. Infection by Leishmania infantum was detected in Lutzomyia longipalpis, Lu. whitmani and Lu. termitophila; L. infantum/L. braziliensis in Lu. longipalpis, Lu. whitmani and Lu. trinidadensis; L. shawi in Lu. longipalpis; L. mexicana in Lu. longipalpis; L. braziliensis in Lu. longipalpis and Lu. whitmani; L. guyanensis in Lu. longipalpis and Lu. termitophila; L. amazonensis in Lu. longipalpis and L. lainsoni or L. naiffi in Lu. longipalpis, while Lu. longipalpis and Lu. trinidadensis were infected with unidentified Leishmania sp. Blood sources were identified in 573 individual phlebotomines and the preferred hosts were, in decreasing order, chicken, dog, rodent and human with lower preferences for pig, horse, opossum and cattle. Lu. longipalpis and Lu. whitmani performed mixed feeding on man, dog and rodent, while Lu. longipalpis was the most opportunistic species, feeding on the blood of all hosts surveyed, but preferably on dog/chicken, dog/rodent and rodent/chicken. Our findings reveal the concomitant circulation of Leishmania species that cause visceral leishmaniasis and tegumentary leishmaniasis in the study area, and explain the occurrence of autochthonous human cases of both clinical forms of leishmaniasis in Caxias, Maranhão. The results support our hypothesis that, in the municipality of Caxias, transmission

  4. Evaluation of two recombinant Leishmania proteins identified by an immunoproteomic approach as tools for the serodiagnosis of canine visceral and human tegumentary leishmaniasis.

    Science.gov (United States)

    Coelho, Eduardo Antonio Ferraz; Costa, Lourena Emanuele; Lage, Daniela Pagliara; Martins, Vívian Tamietti; Garde, Esther; de Jesus Pereira, Nathália Cristina; Lopes, Eliane Gonçalves Paiva; Borges, Luiz Felipe Nunes Menezes; Duarte, Mariana Costa; Menezes-Souza, Daniel; de Magalhães-Soares, Danielle Ferreira; Chávez-Fumagalli, Miguel Angel; Soto, Manuel; Tavares, Carlos Alberto Pereira

    2016-01-15

    Serological diagnostic tests for canine and human leishmaniasis present problems related with their sensitivity and/or specificity. Recently, an immunoproteomic approach performed with Leishmania infantum proteins identified new parasite antigens. In the present study, the diagnostic properties of two of these proteins, cytochrome c oxidase and IgE-dependent histamine-releasing factor, were evaluated for the serodiagnosis of canine visceral (CVL) and human tegumentary (HTL) leishmaniasis. For the CVL diagnosis, sera samples from non-infected dogs living in an endemic or non-endemic area of leishmaniasis, sera from asymptomatic or symptomatic visceral leishmaniasis (VL) dogs, from Leish-Tec(®)-vaccinated dogs, and sera from animals experimentally infected by Trypanosoma cruzi or Ehrlichia canis were used. For the HTL diagnosis, sera from non-infected subjects living in an endemic area of leishmaniasis, sera from active cutaneous or mucosal leishmaniasis patients, as well as those from T. cruzi-infected patients were employed. ELISA assays using the recombinant proteins showed both sensitivity and specificity values of 100% for the serodiagnosis of both forms of disease, with high positive and negative predictive values, showing better diagnostic properties than the parasite recombinant A2 protein or a soluble Leishmania antigen extract. In this context, the two new recombinant proteins could be considered to be used in the serodiagnosis of CVL and HTL. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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    Márcia Ávila A. de Azevedo

    2008-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

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    Nicholas J Gow

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

  8. Participation of ticks in the infectious cycle of canine visceral leishmaniasis, in Teresina, Piauí, Brazil.

    Science.gov (United States)

    Campos, José Henrique Furtado; Costa, Francisco Assis Lima

    2014-01-01

    In this study, we detected Leishmania spp. infection in R. sanguineus collected from dogs that were naturally infected with L. (L.) infantum. We examined 35 dogs of both sexes and unknown ages. The infected dogs were serologically positive by the immunofluorescence antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA), and Quick Test-DPP (Dual Path Platform), as well as parasitological examination of a positive skin biopsy or sternal bone marrow aspiration. Ten negative dogs were included as controls. The ticks that infested these dogs were collected in pools of 10 adult females per animal. The PCR was performed with specific primers for Leishmania spp., which amplified a 720-bp fragment. Of the 35 analyzed samples, a product was observed in eight samples (8/35; 22.9%). We conclude that the presence of parasite DNA suggests that ticks participate in the zoonotic cycle of canine visceral leishmaniasis, in the city of Teresina, Piauí.

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

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    Cláudio Casanova

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

  10. One-year timeline kinetics of cytokine-mediated cellular immunity in dogs vaccinated against visceral leishmaniasis.

    Science.gov (United States)

    Costa-Pereira, Christiane; Moreira, Marcela L; Soares, Rodrigo P; Marteleto, Bruno H; Ribeiro, Vitor M; França-Dias, Michelle H; Cardoso, Ludmila M; Viana, Kelvinson F; Giunchetti, Rodolfo C; Martins-Filho, Olindo A; Araújo, Márcio S S

    2015-04-11

    The main control strategy for visceral leishmaniasis in Brazil has been based on the elimination of seropositive dogs, although this is not widely accepted. In this context, the use of a long-lasting protective vaccine against canine visceral leishmaniasis (CVL) has been highly expected. The aim of this work was to determine the timeline kinetics of the cytokine microenvironment derived from circulating leukocytes as supportive immunological biomarkers triggered by Leishmune® vaccine. Cross-sectional kinetic analysis of cellular immunity cytokines was carried out at three times (1, 6 and 12 months) after primovaccination with Leishmune®. In vitro short-term whole blood cultures were stimulated with Leishmania infantum soluble antigen (SLAg). The secreted cytokine signatures and their major sources were determined. At six months after vaccination, Leishmune® induced an increase in IL-8, IFN-γ, IL-17a and TNF-α levels and a decrease in IL-10. Cytokine signature analysis revealed a shift in the microenvironment towards a pro-inflammatory profile mediated by IL-8 and IFN-γ. Both, CD4(+) (↑TNF-α(+) and ↑IFN-γ (+)) and CD8(+) (↑IL-17a and ↓IL-4) T-cells contributed to the acquired immune responses observed after stimulation with SLAg. The changes observed in the cytokine profile suggested that Leishmune® was able to induce an effective response at six months after primovaccination. After one year, it returned to baseline suggesting the need of additional boosting.

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

    Science.gov (United States)

    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.

  12. Evaluation of cleaving agents other than trypsin in direct agglutination test for further improving diagnosis of visceral leishmaniasis.

    Science.gov (United States)

    el Harith, A; Chowdhury, S; al-Masum, A; Semião-Santos, S; Karim, E; el-Safi, S; Haque, I

    1995-01-01

    Trypsin treatment of Leishmania promastigote antigen has proved to be indispensible in the direct agglutination test (DAT) for the diagnosis of visceral leishmaniasis (VL) and canine visceral leishmaniasis (CVL). In the present study four antigen batches were prepared with pronase (400 micrograms/ml), lipase (0.45% [wt/vol]), pancreatin (0.3% [wt/vol]), or 2-mercaptoethanol (2-ME) (1.2% [vol/vol]) at a ratio of 20:1 versus promastigote packed cell volume or a density of 10(8)/ml. Batches prepared in this way performed satisfactorily when compared with the performance of the initial trypsinated antigen. Even higher was the sensitivity and specificity of the 2-ME-processed antigen, scoring a minimum DAT titer of 1:102,400 in the VL and CVL group and a maximum of 1:400 in the negative control group. Corresponding titers ranging from 1:6,400 to 1:12,800 and 1:800 to 1:1,600 were obtained with the antigen variants processed with pronase, lipase, pancreatin, or trypsin. By combining the use of indigenous Leishmania donovani subspecies from Sudan, Bangladesh, or Morocco and incorporating 2-ME instead of trypsin in the antigen processing step, a threefold increase in titer was attained in sera from the respective areas where VL is endemic. 2-ME-processed antigen suspensions maintained stability at 4 degrees C for up to 9 months, as evidenced by the absence of autoagglutination and the reproducibility of DAT readings with standard sera. The specificity of DAT was further improved by supplementation of the sample diluent with 0.03 M urea and incubation of the test plates at 37 degrees C for 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7559934

  13. Optimizing Insecticide Allocation Strategies Based on Houses and Livestock Shelters for Visceral Leishmaniasis Control in Bihar, India

    Science.gov (United States)

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

    2015-01-01

    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. PMID:25940194

  14. A New Model of Progressive Visceral Leishmaniasis in Hamsters by Natural Transmission via Bites of Vector Sand Flies

    Science.gov (United States)

    Aslan, Hamide; Dey, Ranadhir; Meneses, Claudio; Castrovinci, Philip; Jeronimo, Selma Maria Bezerra; Oliva, Gætano; Fischer, Laurent; Duncan, Robert C.; Nakhasi, Hira L.; Valenzuela, Jesus G.; Kamhawi, Shaden

    2013-01-01

    Background. Visceral leishmaniasis (VL) is transmitted by sand flies. Protection of needle-challenged vaccinated mice was abrogated in vector-initiated cutaneous leishmaniasis, highlighting the importance of developing natural transmission models for VL. Methods. We used Lutzomyia longipalpis to transmit Leishmania infantum or Leishmania donovani to hamsters. Vector-initiated infections were monitored and compared with intracardiac infections. Body weights were recorded weekly. Organ parasite loads and parasite pick-up by flies were assessed in sick hamsters. Results. Vector-transmitted L. infantum and L. donovani caused ≥5-fold increase in spleen weight compared with uninfected organs and had geometric mean parasite loads (GMPL) comparable to intracardiac inoculation of 107–108 parasites, although vector-initiated disease progression was slower and weight loss was greater. Only vector-initiated L. infantum infections caused cutaneous lesions at transmission and distal sites. Importantly, 45.6%, 50.0%, and 33.3% of sand flies feeding on ear, mouth, and testicular lesions, respectively, were parasite-positive. Successful transmission was associated with a high mean percent of metacyclics (66%–82%) rather than total GMPL (2.0 × 104–8.0 × 104) per midgut. Conclusions. This model provides an improved platform to study initial immune events at the bite site, parasite tropism, and pathogenesis and to test drugs and vaccines against naturally acquired VL. PMID:23288926

  15. A new model of progressive visceral leishmaniasis in hamsters by natural transmission via bites of vector sand flies.

    Science.gov (United States)

    Aslan, Hamide; Dey, Ranadhir; Meneses, Claudio; Castrovinci, Philip; Jeronimo, Selma Maria Bezerra; Oliva, Gætano; Fischer, Laurent; Duncan, Robert C; Nakhasi, Hira L; Valenzuela, Jesus G; Kamhawi, Shaden

    2013-04-15

    Visceral leishmaniasis (VL) is transmitted by sand flies. Protection of needle-challenged vaccinated mice was abrogated in vector-initiated cutaneous leishmaniasis, highlighting the importance of developing natural transmission models for VL. We used Lutzomyia longipalpis to transmit Leishmania infantum or Leishmania donovani to hamsters. Vector-initiated infections were monitored and compared with intracardiac infections. Body weights were recorded weekly. Organ parasite loads and parasite pick-up by flies were assessed in sick hamsters. Vector-transmitted L. infantum and L. donovani caused ≥5-fold increase in spleen weight compared with uninfected organs and had geometric mean parasite loads (GMPL) comparable to intracardiac inoculation of 10(7)-10(8) parasites, although vector-initiated disease progression was slower and weight loss was greater. Only vector-initiated L. infantum infections caused cutaneous lesions at transmission and distal sites. Importantly, 45.6%, 50.0%, and 33.3% of sand flies feeding on ear, mouth, and testicular lesions, respectively, were parasite-positive. Successful transmission was associated with a high mean percent of metacyclics (66%-82%) rather than total GMPL (2.0 × 10(4)-8.0 × 10(4)) per midgut. This model provides an improved platform to study initial immune events at the bite site, parasite tropism, and pathogenesis and to test drugs and vaccines against naturally acquired VL.

  16. Epidemiological aspects and spatial distribution of human and canine visceral leishmaniasis in an endemic area in northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Roseane Campos

    2017-05-01

    Full Text Available Visceral leishmaniasis (VL is a systemic disease endemic in tropical countries and transmitted through sand flies. In particular, Canis familiaris (or domesticated dogs are believed to be a major urban reservoir for the parasite causing the disease Leishmania. The average number of human VL cases was 58 per year in the state of Sergipe. The city of Aracaju, capital of Sergipe in Northeastern Brazil, had 159 cases of VL in humans. Correlatively, the percentage of serologically positive dogs for leishmaniasis increased from 4.73% in 2008 to 12.69% in 2014. Thus, these studies aimed to delineate the spatial distribution and epidemiological aspects of human and canine VL as mutually supportive for increased incidence. The number of human cases of VL and the frequency of canine positive serology for VL both increased between 2008 and 2014. Spatial distribution analyses mapped areas of the city with the highest concentration of human and canine VL cases. The neighbourhoods that showed the highest disease frequency were located on the outskirts of the city and in urbanised areas or subjected to development. Exponential increase in VL-positive dogs further suggests that the disease is expanding in urban areas, where it can serve as a reservoir for transmission of dogs to humans via the sand fly vector.

  17. 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

    2016-09-14

    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.

  18. Microscopy and polymerase chain reaction detection of Leishmania chagasi in the pleural and ascitic fluid of a patient with AIDS: Case report and review of diagnosis and therapy of visceral leishmaniasis

    OpenAIRE

    Ada RS Diehl; dos Santos, Rodrigo P; Ricardo Zimmerman; Luz, Letícia P; Tanara Weiss; Pedro Jacobson; Goldani, Luciano Z.

    2004-01-01

    Atypical visceral leishmaniasis is increasingly reported in immunocompromised patients, including patients with AIDS. A case of visceral leishmaniasis in an HIV-infected Brazilian patient with pulmonary and peritoneal involvement is reported. Histological evaluation of pleural fluid and ascites aspirate revealed macrophages with intracellular Leishmania. Polymerase chain reaction analysis was positive for Leishmania in the pleural and ascitic fluid with use of primers specific for Leishmania ...

  19. Evaluation of the immunogenicity and protective efficacy of killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis.

    Science.gov (United States)

    Thakur, Ankita; Kaur, Harpreet; Kaur, Sukhbir

    2015-08-01

    Visceral leishmaniasis (VL) caused by Leishmania donovani is a life-threatening disease involving uncontrolled parasitization of vital organs. Drugs to treat leishmaniasis have one or more limitations or insufficiencies in the long run. A safe and efficacious vaccine to control this disease is needed. Killed antigens that could be safer as vaccines have shown limited efficacy in clinical trials. Immunogenic enhancement with appropriate adjuvants may thus be required to elicit protective immunity based on antibodies and effector T-cell functions. Therefore, it is essential to search for adjuvant to enhance the immunogenicity of killed vaccines and to induce protection against leishmaniasis. So, the aim of the present study was to compare the effectiveness of four adjuvants, i.e. alum, saponin, monophosphoryl lipid A, cationic liposome in combination with Killed Leishmania donovani (KLD) antigen against murine VL. Animals were immunized subcutaneously thrice at an interval of 2 weeks with a final volume of 100 μl per dose. Challenge infection was given 2 weeks after last booster. Mice were sacrificed 15 days after last immunization and on 30, 60 and 90 post-infection/challenge days. The protective efficacy of vaccines was revealed by significant reduction in parasite burden and enhanced DTH responses in comparison with the infected controls. Immunized animals also generated significant levels of Th1 cytokines and increased production of IgG2a, thus indicating the generation of a protective Th1 response. All the adjuvants imparted significant protection, but liposomal formulation was most effective followed by KLD + MPL-A, KLD + saponin, KLD + alum and KLD antigen.

  20. Development of Recombinant Chimeric Antigen Expressing Immunodominant B Epitopes of Leishmania infantum for Serodiagnosis of Visceral Leishmaniasis

    Science.gov (United States)

    Boarino, A.; Scalone, A.; Gradoni, L.; Ferroglio, E.; Vitale, F.; Zanatta, R.; Giuffrida, M. G.; Rosati, S.

    2005-01-01

    Wild canids and domestic dogs are the main reservoir of zoonotic visceral leishmaniasis (VL) caused by Leishmania infantum (syn.: Leishmania chagasi). Serological diagnosis of VL is therefore important in both human and dog leishmaniasis from a clinical and epidemiological point of view. Routine diagnosis of VL is traditionally carried out by immunofluorescent antibody test (IFAT), which is laborious and difficult to standardize and to interpret. In the last decade, however, several specific antigens of Leishmania infantum have been characterized, allowing the development of a recombinant-based immunoassay. Among them, the whole open reading frame encoding K9 antigen, the gene fragment encoding the repetitive sequence of K26, and the 3′-terminal gene fragment of the kinesin-related protein (K39sub) were previously evaluated as diagnostic markers for canine leishmaniasis and proved to be independent in their antibody reactivity. Since sensitivity of serological test is usually higher in multiple-epitope format, in this study the relevant epitopes of K9, K26, and K39 antigens were joined by PCR strategy to produce the chimeric recombinant protein. The resulting mosaic antigen was found highly expressed in Escherichia coli and efficiently purified by affinity chromatography. Antigenic properties of this recombinant antigen were evaluated by indirect enzyme-linked immunosorbent assay (ELISA) using a panel of human and dog sera previously characterized by parasitological and/or serological techniques. Chimeric ELISA showed 99% specificity in both human (n = 180) and canine (n = 343) control groups, while sensitivity was higher in canine VL (96%, n = 213) than in human VL (82%, n = 185). Accordingly, concordance between IFAT and canine chimeric ELISA (k = 0.95, 95% confidence interval = 0.93 to 0.98) was higher than between IFAT and human chimeric ELISA (k = 0.81, 95% confidence interval = 0.76 to 0.87). Results suggest the potential use of this new antigen for routine

  1. Epidemiological aspects of visceral leishmaniasis (kala-azar) in Ceará in the period 2007 to 2011.

    Science.gov (United States)

    Cavalcante, Italo José Mesquita; Vale, Marcus Raimundo

    2014-12-01

    Visceral leishmaniasis (VL; kala-azar) is a serious zoonosis that can be lethal, especially in untreated patients. Due to the fact that the State of Ceará is still an important area of transmission of VL, and based on the constant reports of the urbanization process of the disease in the country, it was necessary to monitor the occurrence of cases of leishmaniasis through epidemiological surveillance. To describe the epidemiology of leishmaniasis cases in Ceará, Brazil. We conducted an epidemiological survey of secondary data provided by SINAN/MS from January 2007 to December 2011. VL is an endemic disease in the State of Ceará, with cases notified in approximately 88% of the municipalities, with an average of 596.8 ± 29.6 cases, an incidence of 6.1 cases/100,000 inhabitants and prevalence of 7.1 cases/100,000 inhabitants. The Metropolitan Region of Fortaleza is the microregion with the largest number of cases reported in state (51.9% of cases), with the capital, Fortaleza, being the municipality with the highest number of cases in the country. Traditionally, the main age group affected by the disease are children; however, a reversal has been observed in the profile from 2008, when the population of adult patients exceeded the pediatric population. Ceará is still an endemic area for VL, and the city of Fortaleza reported the highest number of cases in the country. In the State, a change in the profile of patients with the disease has been observed, now affecting primarily adults.

  2. Sequential chemoimmunotherapy of experimental visceral leishmaniasis using a single low dose of liposomal amphotericin B and a novel DNA vaccine candidate.

    Science.gov (United States)

    Seifert, Karin; Juhls, Christiane; Salguero, Francisco J; Croft, Simon L

    2015-09-01

    Combination therapies for leishmaniasis, including drugs and immunomodulators, are one approach to shorten treatment courses and to improve the treatment of complex manifestations of the disease. We evaluated a novel T-cell-epitope-enriched DNA vaccine candidate (LEISHDNAVAX) as host-directed immunotherapy in combination with a standard antileishmanial drug in experimental visceral leishmaniasis. Here we show that the DNA vaccine candidate can boost the efficacy of a single suboptimal dose of liposomal amphotericin B in C57BL/6 mice. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. Real-time PCR in detection and quantitation of Leishmania donovani for the diagnosis of Visceral Leishmaniasis patients and the monitoring of their response to treatment.

    Science.gov (United States)

    Hossain, Faria; Ghosh, Prakash; Khan, Md Anik Ashfaq; Duthie, Malcolm S; Vallur, Aarthy C; Picone, Alessandro; Howard, Randall F; Reed, Steven G; Mondal, Dinesh

    2017-01-01

    Sustained elimination of Visceral Leishmaniasis (VL) requires the reduction and control of parasite reservoirs to minimize the transmission of Leishmania donovani infection. A simple, reproducible and definitive diagnostic procedure is therefore indispensable for the early and accurate detection of parasites in VL, Relapsed VL (RVL) and Post Kala-azar Dermal Leishmaniasis (PKDL) patients, all of whom are potential reservoirs of Leishmania parasites. To overcome the limitations of current diagnostic approaches, a novel quantitative real-time polymerase chain reaction (qPCR) method based on Taqman chemistry was devised for the detection and quantification of L. donovani in blood and skin. The diagnostic efficacy was evaluated using archived peripheral blood buffy coat DNA from 40 VL, 40 PKDL, 10 RVL, 20 cured VL, and 40 cured PKDL along with 10 tuberculosis (TB) cases and 80 healthy endemic controls. Results were compared to those obtained using a Leishmania-specific nested PCR (Ln-PCR). The real time PCR assay was 100% (95% CI, 91.19-100%) sensitive in detecting parasite genomes in VL and RVL samples and 85.0% (95% CI, 70.16-94.29%) sensitive for PKDL samples. In contrast, the sensitivity of Ln-PCR was 77.5% (95% CI, 61.55-89.16%) for VL samples, 100% (95%CI, 69.15-100%) for RVL samples, and 52.5% (95% CI, 36.13-68.49%) for PKDL samples. There was significant discordance between the two methods with the overall sensitivity of the qPCR assay being considerably higher than Ln-PCR. None of the assay detected L. donovani DNA in buffy coats from cured VL cases, and reduced infectious burdens were demonstrated in cured PKDL cases who remained positive in 7.5% (3/40) and 2.5% (1/40) cases by real-time PCR and Ln-PCR, respectively. Both assays were 100% (95% CI, 95.98-100) specific with no positive signals in either endemic healthy control or TB samples. The real time PCR assay we developed offers a molecular tool for accurate detection of circulating L. donovani parasites

  4. Real-time PCR in detection and quantitation of Leishmania donovani for the diagnosis of Visceral Leishmaniasis patients and the monitoring of their response to treatment

    Science.gov (United States)

    Ghosh, Prakash; Khan, Md. Anik Ashfaq; Duthie, Malcolm S.; Vallur, Aarthy C.; Picone, Alessandro; Howard, Randall F.; Reed, Steven G.

    2017-01-01

    Sustained elimination of Visceral Leishmaniasis (VL) requires the reduction and control of parasite reservoirs to minimize the transmission of Leishmania donovani infection. A simple, reproducible and definitive diagnostic procedure is therefore indispensable for the early and accurate detection of parasites in VL, Relapsed VL (RVL) and Post Kala-azar Dermal Leishmaniasis (PKDL) patients, all of whom are potential reservoirs of Leishmania parasites. To overcome the limitations of current diagnostic approaches, a novel quantitative real-time polymerase chain reaction (qPCR) method based on Taqman chemistry was devised for the detection and quantification of L. donovani in blood and skin. The diagnostic efficacy was evaluated using archived peripheral blood buffy coat DNA from 40 VL, 40 PKDL, 10 RVL, 20 cured VL, and 40 cured PKDL along with 10 tuberculosis (TB) cases and 80 healthy endemic controls. Results were compared to those obtained using a Leishmania-specific nested PCR (Ln-PCR). The real time PCR assay was 100% (95% CI, 91.19–100%) sensitive in detecting parasite genomes in VL and RVL samples and 85.0% (95% CI, 70.16–94.29%) sensitive for PKDL samples. In contrast, the sensitivity of Ln-PCR was 77.5% (95% CI, 61.55–89.16%) for VL samples, 100% (95%CI, 69.15–100%) for RVL samples, and 52.5% (95% CI, 36.13–68.49%) for PKDL samples. There was significant discordance between the two methods with the overall sensitivity of the qPCR assay being considerably higher than Ln-PCR. None of the assay detected L. donovani DNA in buffy coats from cured VL cases, and reduced infectious burdens were demonstrated in cured PKDL cases who remained positive in 7.5% (3/40) and 2.5% (1/40) cases by real-time PCR and Ln-PCR, respectively. Both assays were 100% (95% CI, 95.98–100) specific with no positive signals in either endemic healthy control or TB samples. The real time PCR assay we developed offers a molecular tool for accurate detection of circulating L

  5. 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

  6. 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. 

  7. Long-term use of an antiinflammatory, curcumin, suppressed type 1 immunity and exacerbated visceral leishmaniasis in a chronic experimental model

    OpenAIRE

    Adapala, Nagasuresh; Chan, Marion M.

    2008-01-01

    Inflammation is considered the underlying cause of numerous disorders, and the practice of taking antiinflammatories as diet supplements has become increasingly prevalent. This study addresses the bioavailablity of a well-established dietary antiinflammatory, curcumin, and examines its effect on adaptive immunity. Visceral leishmaniasis is a major parasitic disease which protection relies on cell-mediated immunity and production of nitric oxide. We found that long-term, low-dose, oral consump...

  8. Factores de riesgo, representaciones y prácticas asociadas con la leishmaniasis visceral humana en un foco urbano emergente en Posadas, Argentina

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    Karen López

    2016-04-01

    Conclusión. Se observó que la pobreza estructural constituía un factor social determinante del riesgo, y que aumentaba la probabilidad de contacto entre humanos y vectores por la mala calidad de la vivienda y el hacinamiento. El factor de riesgo más importante para la leishmaniasis visceral humana fue la tenencia en el domicilio de perros con la enfermedad.

  9. Visceral leishmaniasis and immunocompromise as a risk factor for the development of visceral leishmaniasis: a changing pattern at the hospital for tropical diseases, london.

    Directory of Open Access Journals (Sweden)

    Kate Fletcher

    Full Text Available A retrospective study of imported VL to the HTD, London including patients diagnosed and/or managed at the HTD between January 1995 and July 2013. We analyse patient demographics, risk factors for developing VL, diagnosis, investigation, management and outcome. Twenty-eight patients were treated for VL at the HTD over an 18 year period. The median age at VL diagnosis was 44 years (range 4-87 years with a male to female ratio of 2:1. Most patients were British and acquired their infection in the Mediterranean basin. The median time from first symptom to diagnosis was six months with a range of 1-12 months and diagnosis included microscopic visualisation of leishmania amastigotes, positive serological tests (DAT and k39 antibody or identification of leishmania DNA. Nineteen patients had some form of immunocompromise and this has increased proportionally compared to previously described data. Within the immunocompromised group, the ratio of those with autoimmune disease has increased. Immunocompromised patients had lower cure and higher relapse rates.The rise of VL in patients with immunocompromise secondary to autoimmune disease on immunomodulatory drugs presents new diagnostic and therapeutic challenges. VL should be a differential diagnosis in immunocompromised patients with pyrexia of unknown origin returning from travel in leishmania endemic areas.

  10. Imaging visceral leishmaniasis in real time with golden hamster model: Monitoring the parasite burden and hamster transcripts to further characterize the immunological responses of the host.

    Science.gov (United States)

    Rouault, Eline; Lecoeur, Hervé; Meriem, Asma Ben; Minoprio, Paola; Goyard, Sophie; Lang, Thierry

    2017-02-01

    Characterizing the clinical, immunological and parasitological features associated with visceral leishmaniasis is complex. It involves recording in real time and integrating quantitative multi-parametric data sets from parasite infected host tissues. Although several models have been used, hamsters are considered the bona fide experimental model for Leishmania donovani studies. To study visceral leishmaniasis in hamsters we generated virulent transgenic L. donovani that stably express a reporter luciferase protein. Two complementary methodologies were combined to follow the infectious process: in vivo imaging using luciferase-expressing Leishmania and real time RT-PCR to quantify both Leishmania and host transcripts. This approach allows us: i) to assess the clinical outcome of visceral leishmaniasis by individual monitoring of hamster weight, ii) to follow the parasite load in several organs by real time analysis of the bioluminescence in vivo and through real time quantitative PCR analysis of amastigote parasite transcript abundance ex vivo, iii) to evaluate the immunological responses triggered by the infection by quantifying hamster transcripts on the same samples and iv) to limit the number of hamsters selected for further analysis. The overall data highlight a correlation between the transcriptional cytokine signatures of hamster affected tissues and the amastigote burden fluctuations, thus providing new insights into the immunopathological process driven by L. donovani in the tissues of mammalian hosts. Finally, they suggest organ-specific immune responses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. 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 interl......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...... only IFN-gamma. This is the first report of a Th1- and Th2-type response in human leishmaniasis. These results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections. Preferential activation of IL-4-producing Th2-like cells may...... be involved in the exacerbation of human VL, whereas activation of IFN-gamma-producing Th1 cells may protect the host from severe disease. Identification of leishmanial antigens activating one or the other type of T cells will be important in the development of vaccines against leishmaniasis....

  12. [The species composition and epidemiological significance of mosquitoes (Diptera, Psychodidae, Phlebotominae) in the foci of visceral leishmaniasis in the Papsky District, Namangan Region, Uzbekistan].

    Science.gov (United States)

    Ponirovskiĭ, E N; Zhirenkina, E N; Strelkova, M V; Baranets, M S; Fatullaeva, A A; Ponomareva, V I; Kovalenko, D A; Nasyrova, R M; Razakov, Sh A; Shonian, G

    2012-01-01

    In 2008, mosquito observations were made in 4 populated areas of the Papsky District, Namangan Region, Uzbekistan (Fergana Valley), where visceral leishmaniasis cases had been registered. The mosquitoes were caught in Oltinkan, Gulistan, Chodak, and Chorkesar in July and in Oltinkan in September. A total of 7245 mosquitoes were caught in the living and utility premises during the observation period. The mosquito fauna of this focus was found to represent 10 species: P. papatasi, P. sergenti, P. alexandri, P. caucasicus, P. nuri, P. keshishiani, P. angustus, P. longiductus, S. grecovi, and S. sumbarica. It also contained P. papatasi, a vehicle for transmission of zoonotic cutaneous leishmaniasis, P. sergenti, an anthroponotic cutaneous leishmaniasis vehicle, and P. longiductus, a visceral leishmaniasis one. The major site of hatching and habitat for mosquitoes were utility premises for large and small cattle. A polymerase chain reaction was used to determine mosquito infestation with L. infantum. A total of 38 female pools of 5 species: P. papatasi, P. sergenti, P. keshishiani, P. angustus, and P. longiductus were tested. Testing of female mosquitoes for L. infantum yielded a negative result.

  13. Leishmaniose visceral canina em três bairros de Uruguaiana - RS | Canine visceral leishmaniasis in three districts of Uruguaiana - RS

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    Laura Ilarraz Massia

    2016-02-01

    Full Text Available Este estudo teve como objetivo descrever a situação da Leishmaniose visceral canina (LCV em Uruguaiana quanto aos casos confirmados a partir de 2009 e à existência de associação entre o perfil socioeconômico e nível de conhecimento da população sobre a enfermidade em três bairros do município. Apesar da maioria dos entrevistados informar possuir conhecimento sobre a LVC, observou-se dificuldade em adotar uma das medidas preconizadas para a prevenção da doença (poder comprar a coleira. Houve associação entre renda e conhecimento sobre LVC (p = 0,04, poder comprar a coleira (p = 0,00 e limpar o pátio (p = 0,01. Entretanto, não se observou associação entre esta variável e achar que existe tratamento (p = 0,14 ou possuir pátio cercado (p = 0,13. Verificou-se também associação entre grau de escolaridade e conhecimento sobre LVC, poder comprar a coleira e achar que existe tratamento (p = 0,00. As informações resultantes da pesquisa podem auxiliar na condução de políticas públicas para a prevenção e controle da LVC. ================================================= This study aimed to describe the situation of LVC in Uruguaiana about the confirmed cases from 2009 and the existence of association between socioeconomic status and people’s level of knowledge about the disease in three districts of the municipality. Although the majority of respondents report having knowledge of the LVC, it found it difficult to adopt one of the measures recommend for the prevention of disease (to buy the collar. There was an association between income and knowledge of LVC (p = 0.04, to buy the collar (p = 0.00 and clean the patio (p = 0.01. However, there was no association between this variable and find that no treatment (p = 0.14 or own fenced yard (p = 0.13. It was also found association between level of education and knowledge of LVC, to buy the collar and you think there is treatment (p = 0.00. The resulting research information

  14. 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....

  15. Reposição de cães em área endêmica para leishmaniose visceral Dog replacement in an area endemic for visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Andréa Maria Andrade

    2007-10-01

    Full Text Available Esse trabalho objetivou estimar a reposição de cães em área endêmica para leishmaniose visceral, onde a eutanásia de animais soropositivos é indicada como medida de controle, e avaliar os motivos que levaram a aquisição ou não de novos animais. Houve a reposição em 44,5% dos casos, principalmente devido à necessidade de companhia ou guarda. O principal motivo para a não-reposição foi o temor da leishmaniose visceral.This study aimed to estimate the dog replacement rate in an area endemic for visceral leishmaniasis, in which slaughter of seropositive animals was indicated as a control measure, and to evaluate the reasons why new animals were or were not acquired. The animals were replaced in 44.5% of the cases, and this was done mainly because of the need for a companion or guard dog. The main reason for not replacing the dog was fear of visceral leishmaniasis.

  16. Quantification of the response to miltefosine treatment for visceral leishmaniasis by QT-NASBA

    NARCIS (Netherlands)

    de Vries, P. J.; van der Meide, W. F.; Godfried, M. H.; Schallig, H. D. F. H.; Dinant, H. J.; Faber, W. R.

    2006-01-01

    A male patient with psoriatic arthritis and visceral Leishmania infantum infection was treated with oral miltefosine 50 mg three times a day for 4 weeks at the Academic Medical Center, Amsterdam, The Netherlands. Miltefosine plasma concentrations were measured with liquid chromatography/mass

  17. Vaccines for canine leishmaniasis.

    Science.gov (United States)

    Foroughi-Parvar, Faeze; Hatam, Gholamreza

    2014-01-01

    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.

  18. 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.

  19. Molecular Characterization of Leishmania Parasites in Giemsa-Stained Slides from Cases of Human Cutaneous and Visceral Leishmaniasis, Eastern Algeria.

    Science.gov (United States)

    Beldi, Nadia; Mansouri, Roukaya; Bettaieb, Jihene; Yaacoub, Alia; Souguir Omrani, Hejer; Saadi Ben Aoun, Yusr; Saadni, Farida; Guizani, Ikram; Guerbouj, Souheila

    2017-06-01

    In Algeria, visceral leishmaniasis (VL) is due to Leishmania (L.) infantum, while three cutaneous forms (CL) are caused by Leishmania major, Leishmania tropica and Leishmania infantum. In this study, the use of Giemsa-stained slides was evaluated with two PCR techniques, in Eastern Algeria. A total of 136 samples corresponding to 100 CL smears (skin scrapings) and 36 VL slides (bone marrow aspirates) collected from 2008 to 2014 were tested. Upon DNA extraction, two PCRs were used to amplify the ribosomal Internal Transcribed Spacer 1 (ITS1) and mini-exon genes. Amplified products were digested (PCR-RFLP) and profiles analyzed for Leishmania species identification. A statistical analysis was also performed. ITS1-PCR was found significantly more sensitive than mini-exon-PCR (77.95% positives vs. 67.65%; p = 0.001). Comparison of PCR positivity showed statistically significant differences between old and recently prepared slides suggesting a better use of recent slides in PCR analyses. For species identification, PCR-restriction fragment length polymorphism (RFLP) results of ITS1 and mini-exon were concordant. L. infantum was identified from VL cases and L. infantum, L. major, and L. tropica from CL ones. According to geographical origin, L. infantum was found in North-Eastern provinces, while L. major was distributed from the North to the Center-East of Algeria. Interestingly, two L. tropica samples were identified in Annaba, located far North-East Algeria. Distribution of leishmaniasis in Eastern parts of Algeria, besides finding of L. tropica in the far North, is in this study described for the first time using molecular tools, thus confirming the usefulness of slides for PCR identification of Leishmania parasites in retrospective epidemiological investigations.

  20. 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; Carvalho, Luiz Otávio Alves de; Pereira, Agnes Antônia Sampaio; Rugani, Jerônimo Marteleto Nunes; Rego, Felipe Dutra; Gontijo, Célia Maria Ferreira; Andrade, José Dilermando

    2017-04-01

    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. 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. 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. 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. 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.

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

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    David M Poché

    2016-08-01

    Full Text Available 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.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.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.

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

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    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)

  3. Prevalence of malnutrition and associated risk factors among adult visceral leishmaniasis patients in Northwest Ethiopia: a cross sectional study.

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    Mengesha, Bewketu; Endris, Mengistu; Takele, Yegnasew; Mekonnen, Kalehiwot; Tadesse, Takele; Feleke, Amsalu; Diro, Ermias

    2014-02-04

    Visceral leishmaniasis (VL) causes considerable morbidity and mortality in Ethiopia. Data on the prevalence and associated risk factors on malnutrition among VL patients in Ethiopia are scarce. This study aimed to assess the prevalence of malnutrition and its associated risk factor among VL patients in Northwest Ethiopia. An institution-based cross-sectional study was conducted from June to September 2012 at four leishmaniasis treatment sites in Northwest Ethiopia. Four hundred and three adult VL patients were enrolled in the study. Malnutrition was defined as a body mass index (BMI) ≤ 18.5 kg/m2. The data collected from the VL patients included sex, age, residence, occupation, weight, height, laboratory results (HIV, hemoglobin, intestinal parasites). Multivariate logistic regression model was used to determine the strength of association between malnutrition and associated risk factors. Among 403 adult VL patients 385 (95.5%) were malnourished. Twenty eight percent (n = 113), 30.3% (n = 122), and 37.2% (n = 150) were mildly, moderately and severely malnourished, respectively. The prevalence of intestinal parasitic infection was 47.6% (n = 192) and it was associated with malnutrition (P = 0.01). The prevalence of VL-HIV co-infection was 10.4% (n = 42). Hook worm, Giardia intestinalis and Ascaris lumbircoides were the leading prevalent intestinal parasites. Factors such as age, sex, residence, occupation, HIV status and anemia were not associated with severe malnutrition. The prevalence of malnutrition in VL patients was very high and it was associated with intestinal parasitic infections. Therefore, screening of severely malnourished VL patients for intestinal parasitic infections during admission is recommended.

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

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    Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L

    2014-01-01

    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, subunit, 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 Leishmania 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 LdCen(-/-) 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 in normal

  5. The role of rk39 serologic test in the diagnosis of visceral leishmaniasis in a Tertiary Hospital, Northern Ethiopia.

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    Kiros, Yazezew Kebede; Regassa, Bethlhem Feleke

    2017-04-26

    The study is done in Ayder Referral Hospital in Northern Ethiopia. Ethiopia is one of the countries where visceral leishmaniasis (VL) is endemic. Diagnosis of VL in Ethiopia is primarily based on rK39 immunochromatographic (rk39-ICT) strip. This test has been shown to have variable sensitivity and specificity in different countries. Hence the objective of the study is to determine the sensitivity and specificity of rk39-ICT in the diagnosis of VL in our set up. The study participants were VL suspected patients admitted to the hospital. A cross sectional study design was used. The study was conducted from January 14, 2013 to June 26, 2015. The rK39-ICT strip used was the InBios brand. Ethical clearance was obtained from the IRB of the college and written consent was obtained from the individual patients. A total of 62 VL suspects were involved in the study. The mean age was 26.3 years (SD = 6.94 years) with a median age of 25.5 years. Sixty-one (98.4%) of the patients was males. The rK39-ICT was positive in 50 (80.6%) of the patients. Splenic aspiration was positive in 44 (71%) of the patients. In 37 (59.7%) of the patients both rK39 and splenic aspiration were positive. Thirteen (21%) of the patients had positive rK39 but negative splenic aspiration. Five (8.1%) of the patients had both negative rK39 and splenic aspiration however seven (11.3%) of the patients had rk39 negative but splenic aspiration positive. The sensitivity, specificity, positive predictive value and the negative predictive value of rK39-ICT, taking splenic aspiration as a gold standard test, is 84.1% (95% CI 69.9-93.4%), 27.8% (95% CI 9.7-53.5%), 74.0% (95% CI 60-85.4%) and 41.7% (95% CI 15.2-72.3%) respectively. Sensitivity of rK39-ICT is low and its specificity is poor in our set up. Significant number of patients with confirmed VL did not have travel history to endemic areas. We recommend that the rK39-ICT needs improvement for clinical use in our set up and case definition for visceral

  6. Biomarkers of Safety and Immune Protection for Genetically Modified Live Attenuated Leishmania Vaccines Against Visceral Leishmaniasis – Discovery and Implications

    Science.gov (United States)

    Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L.

    2014-01-01

    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, subunit, 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 Leishmania 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 LdCen−/− 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 in normal

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

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    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

  8. 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.

  9. 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

  10. 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

  11. Water-soluble polymer–drug conjugates for combination chemotherapy against visceral leishmaniasis

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    Nicoletti, Salvatore; Seifert, Karin; Gilbert, Ian H.

    2010-01-01

    There is a need for new safe, effective and short-course treatments for leishmaniasis; one strategy is to use combination chemotherapy. Polymer–drug conjugates have shown promise for the delivery of anti-leishmanial agents such as amphotericin B. In this paper, we report on the preparation and biological evaluation of polymer–drug conjugates of N-(2-hydroxypropyl)methacrylamide (HPMA), amphotericin B and alendronic acid. The combinatorial polymer–drug conjugates were effective anti-leishmanial agents in vitro and in vivo, but offered no advantage over the single poly(HPMA)–amphotericin B conjugates. PMID:20338769

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

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    Galvis-Ovallos Fredy

    2017-01-01

    Full Text Available 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.

  13. 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.

  14. Serological and molecular tools to diagnose visceral leishmaniasis: 2-years' experience of a single center in Northern Italy.

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    Stefania Varani

    Full Text Available The diagnosis of visceral leishmaniasis (VL remains challenging, due to the limited sensitivity of microscopy, the poor performance of serological methods in immunocompromised patients and the lack of standardization of molecular tests. The aim of this study was to implement a combined diagnostic workflow by integrating serological and molecular tests with standardized clinical criteria. Between July 2013 and June 2015, the proposed workflow was applied to specimens obtained from 94 in-patients with clinical suspicion of VL in the Emilia-Romagna region, Northern Italy. Serological tests and molecular techniques were employed. Twenty-one adult patients (22% had a confirmed diagnosis of VL by clinical criteria, serology and/or real-time polymerase chain reaction; 4 of these patients were HIV-positive. Molecular tests exhibited higher sensitivity than serological tests for the diagnosis of VL. In our experience, the rK39 immunochromatographic test was insufficiently sensitive for use as a screening test for the diagnosis of VL caused by L. infantum in Italy. However, as molecular tests are yet not standardized, further studies are required to identify an optimal screening test for Mediterranean VL.

  15. Clinical and Microbiological Characteristics of Visceral Leishmaniasis Outbreak in a Northern Italian Nonendemic Area: A Retrospective Observational Study

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    E. Franceschini

    2016-01-01

    Full Text Available Background. Visceral leishmaniasis (VL caused by Leishmania infantum is endemic in the Mediterranean area. In the last decades a northward spread of the parasite has been observed in Italy. This paper describes a VL outbreak in Modena province (Emilia-Romagna, Northern Italy between 2012 and 2015. Methods. Retrospective, observational study to evaluate epidemiological, microbiological characteristics, and clinical management of VL in patients referring to Policlinico Modena Hospital. Results. Sixteen cases of VL occurred in the study period. An immunosuppressive condition was present in 81.3%. Clinical presentation included anemia, fever, leukopenia, thrombocytopenia, and hepatosplenomegaly. Serology was positive in 73.3% of cases, peripheral blood PCR in 92.3%, and bone marrow blood PCR in 100%. Culture was positive in 3/6 cases (50% and all the isolates were identified as L. infantum by ITS1/ITS2 sequencing. The median time between symptom onset and diagnosis was 22 days (range 6–131 days. All patients were treated with liposomal amphotericin b. 18.8% had a VL recurrence and were treated with miltefosine. Attributable mortality was 6.3%. Conclusions. VL due to L. infantum could determine periodical outbreaks, as the one described; thus it is important to include VL in the differential diagnosis of fever of unknown origin, even in low-endemic areas.

  16. Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil

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    Lucas S Magalhães

    Full Text Available BACKGROUND Treatment-refractory visceral leishmaniasis (VL has become an important problem in many countries. OBJECTIVES We evaluated the antimony-resistance mechanisms of Leishmania infantum isolated from VL patients refractory or responsive to treatment with pentavalent antimony. METHODS Strains isolated from antimony-refractory patients (in vitro antimony-resistant isolates and antimony-responsive patients (in vitro antimony-sensitive isolates were examined. Morphological changes were evaluated by transmission electron microscopy after trivalent antimony exposure. P-glycoprotein (P-gp efflux pump activity was evaluated using the pump-specific inhibitor verapamil hydrochloride, and the role of thiol in trivalent antimony resistance was investigated using the enzymatic inhibitor L-buthionine sulfoximine. FINDINGS Antimony treatment induced fewer alterations in the cellular structure of L. infantum resistant isolates than in that of sensitive isolates. P-gp efflux activity was not involved in antimony resistance in these isolates. Importantly, the resistant isolates contained higher levels of thiol compared to the sensitive isolates, and inhibition of thiol synthesis in the resistant isolates recovered their sensitivity to trivalent antimony treatment, and enhanced the production of reactive oxygen species in promastigotes exposed to the drug. MAIN CONCLUSIONS Our results demonstrate that isolates from patients with antimony-refractory VL exhibited higher thiol levels than antimony-sensitive isolates. This indicates that redox metabolism plays an important role in the antimony-resistance of New World VL isolates.

  17. Development and Assessment of Loop-Mediated Isothermal Amplification (LAMP Assay for the Diagnosis of Human Visceral Leishmaniasis in Iran.

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    Mehrdad Ghasemian

    2014-03-01

    Full Text Available Parasitological methods for the diagnosis of Visceral leishmaniasis (VL require invasive procedures, so serological and molecular approaches have been developed but are not generally applicable in the field. We evaluated a loop mediated isothermal amplification (LAMP assay using blood from VL patients and compared it to nested PCR.Forty-seven subjects with clinical features (fever, hepatosplenomegaly and anemia were confirmed positive for VL by the direct agglutination test (DAT at titers >3200. Forty DAT negative individuals from non-endemic areas with no clinical signs or symptoms of VL served as controls. A LAMP assay was performed using a set of six primers targeting Leishmania infantum kinetoplast DNA (kDNA minicircle gene under isothermal (64 °C conditions. For nested PCR we used primers targeting the kDNA minicircle gene.The LAMP assay provided a detection limit of 1 parasite in 1 ml of peripheral blood and detected L. infantum DNA in 44 of 47 DAT-confirmed VL cases, with diagnostic sensitivity of 93.6% (95% CI. No L. infantum DNA was amplified in controls, indicating a specificity of 100%. The nested PCR yielded sensitivity of 96% (95% CI and a specificity of 100% (95% CI.The LAMP assay gave results similar to those of nested PCR but in a shorter time. The LAMP method is simple; requires no sophisticated equipment; has a short reaction time; and results, indicated by turbidity of the reaction mixture, are observable with the naked eye.

  18. Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil.

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    Magalhães, Lucas S; Bomfim, Lays Gs; Mota, Sthefanne G; Cruz, Geydson S; Corrêa, Cristiane B; Tanajura, Diego M; Lipscomb, Michael W; Borges, Valéria M; Jesus, Amélia R de; Almeida, Roque P de; Moura, Tatiana R de

    2018-02-01

    BACKGROUND Treatment-refractory visceral leishmaniasis (VL) has become an important problem in many countries. OBJECTIVES We evaluated the antimony-resistance mechanisms of Leishmania infantum isolated from VL patients refractory or responsive to treatment with pentavalent antimony. METHODS Strains isolated from antimony-refractory patients (in vitro antimony-resistant isolates) and antimony-responsive patients (in vitro antimony-sensitive isolates) were examined. Morphological changes were evaluated by transmission electron microscopy after trivalent antimony exposure. P-glycoprotein (P-gp) efflux pump activity was evaluated using the pump-specific inhibitor verapamil hydrochloride, and the role of thiol in trivalent antimony resistance was investigated using the enzymatic inhibitor L-buthionine sulfoximine. FINDINGS Antimony treatment induced fewer alterations in the cellular structure of L. infantum resistant isolates than in that of sensitive isolates. P-gp efflux activity was not involved in antimony resistance in these isolates. Importantly, the resistant isolates contained higher levels of thiol compared to the sensitive isolates, and inhibition of thiol synthesis in the resistant isolates recovered their sensitivity to trivalent antimony treatment, and enhanced the production of reactive oxygen species in promastigotes exposed to the drug. MAIN CONCLUSIONS Our results demonstrate that isolates from patients with antimony-refractory VL exhibited higher thiol levels than antimony-sensitive isolates. This indicates that redox metabolism plays an important role in the antimony-resistance of New World VL isolates.

  19. Leishmania infantum-induced primary and challenge infections in rhesus monkeys (Macaca mulatta): a primate model for visceral leishmaniasis.

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    Porrozzi, R; Pereira, M S; Teva, A; Volpini, A C; Pinto, M A; Marchevsky, R S; Barbosa, A A; Grimaldi, G

    2006-10-01

    Visceral leishmaniasis (VL) was experimentally induced in rhesus macaques (Macaca mulatta) by intravenously inoculating 2 x 10(7)amastigotes/kg of body weight of Leishmania infantum. The macaques developed a systemic disease showing characteristic features of human VL such as fever, diarrhoea, body weight loss, anaemia, hypergammaglobulinaemia and transient lymphocytosis, as well as lymph node, liver and/or spleen enlargement. Nine weeks after infection, one primate showed pronounced weight loss, became moribund and was euthanized. The necropsy findings included granulomas composed of parasite-containing macrophages, lymphocytes and plasma cells in the liver, spleen and lymph nodes. The remaining macaques had a sustained course of infection but developed a mild-to-moderate illness that subsequently showed evidence of self-cure. Of note, pathological findings included a typical cell-mediated immunity-induced granulomatous reaction that had an effect on the control of parasite replication. All infected monkeys responded with increased production of anti-Leishmania-specific IgG antibodies. Despite the fact that clinical resistance to L. infantum was not consistently associated with a parasite-specific cell-mediated immune response, drug-cured macaques from the primary infection acquired immunity to homologous re-infection. These findings point to the feasibility of using the L. infantum macaque model for pre-clinical evaluation of novel chemotherapeutics or vaccine candidates for human VL.

  20. [Parasitological, immunohistochemical and histopathological study for Leishmania chagasi detection in splenic tissues of dogs with visceral leishmaniasis].

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    Tasca, Karen Ingrid; Buzetti, Wilma Aparecida Starke; Tenorio, Michely da Silva; Paulan, Silvana de Cássia; Lima, Flávia Luna; de Queiroz, Nina Mari Gual Pimenta; Machado, Rosângela Zacarias; Oliveira, Tricia Maria Ferreira de Souza; Neves, Maria Francisca; de Noronha, Antonio Carlos Faconti; de Assis, Juliana

    2009-01-01

    The purpose of this work was a Canine Visceral Leishmaniasis--CVL study by parasitological direct examination of Leishmania (L.) chagasi (imprinting and histological), immunohistochemical test and histopathological analysis using spleen tissues from 34 dogs euthanized by the Zoonotic Disease Control Centre from Ilha Solteira, SP, Brazil. According to the clinical signs, the dogs were divided in three groups: asymptomatics (8 dogs), oligosymptomatics (17 dogs) and symptomatics (9 dogs). After the accomplishment of all diagnostic tests, 22 dogs were considered positives (64.7%) and 12 (35.3%) were negatives to CVL. From these positive dogs, 1/22 (4.5%) was asymptomatic, 12/22(54.5%) were oligosymptomatics and 8/22 (40.1%) were symptomatics. The histopathological study in spleen tissues from positive, especially symptomatic dogs, showed a diffuse chronic inflammation with thickness of capsular and trabecular regions and there was extensive morphologic alteration of the red and white pulp by the presence of abundant macrophages full with amastigotes, the granulomatous inflammatory reaction and haemorrhagic areas. The data of this work from histopathologic examination and direct microscopic visualization of L. (L.) chagasi showed that the spleen was an useful organ to collect sample tissues for CVL diagnosis. The immunostaining detected the highest number of positive dogs and were considered an important and conclusive method to be used in addition to parasitological methods for CVL, particularly in asymptomatic or oligosymptomatic dogs.

  1. 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.

  2. [Canine visceral leishmaniasis diagnosis by immunohistochemistry and PCR in skin tissues in association with IFAT and ELISA-test].

    Science.gov (United States)

    de Queiroz, Nina M G P; de Assis, Juliana; Oliveira, Trícia M F S; Machado, Rosângela Z; Nunes, Cáris M; Starke-Buzetti, Wilma A

    2010-01-01

    The purpose of the present study was to evaluate the immunohistochemistry (IMHC) and PCR (Polymerase Chain Reaction) tests for Canine Visceral Leishmaniasis (CVL) diagnosis and compare the results with serological tests such as the indirect fluorescence antibody test (IFAT), ELISA and a parasitological test (microscopic direct examination of the parasite stained with haematoxylin and eosin--HE). For this study, samples of healthy or lesion skin tissues were obtained from 34 CVL naturally infected dogs classified in three groups: asymptomatic, oligosymptomatic and polisymptomatic. Not only lesion (56.5%) but also healthy skins (31.8%) were positives by IMHC and confirmed by PCR in 97.8% of skin samples. In asymptomatic group, 87.5% dogs were negatives by serological tests, but positives by IMHC in 50% and by PCR in 100%. In oligosymptomatic group, 100%, 85.7% and 28.6% of dogs were positives, respectively by PCR, serological and IMHC tests. In addition, 91.7% of polisymptomatic dogs were serum positive and had intact parasites in the skin. In general, PCR showed higher positivity (100%). The efficiency of each test varied with the evolution of the disease. IMHC may be used to confirm the results of the serology and PCR in inconclusive cases after HE and IMHC. The association of techniques proposed in this study may increase the positivity and contributed to the control of this canine disease.

  3. 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.

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

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    Aracele Tenório de Almeida e Cavalcanti

    2012-02-01

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

  5. 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.

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

    Science.gov (United States)

    Mohebali, Mehdi; Arzamani, Kourosh; Zarei, Zabiholah; Akhoundi, Behnaz; Hajjaran, Homa; Raeghi, Saber; Heidari, Zahra; Motavalli-Haghi, Seyed Mousa; Elikaee, Samira; Mousazadeh-Mojarrad, Ahmad; Kakoei, Zahra

    2016-12-01

    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. 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. 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. The present study showed that sylvatic cycle of L. infantum had been established in the studied endemic areas of VL in northeastern Iran.

  7. The Cytotoxic T Lymphocyte Antigen-4 +49A/G Single Nucleotide Polymorphism Association With Visceral Leishmaniasis.

    Science.gov (United States)

    Hajilooi, Mehrdad; Lotfi, Pegah; Seif, Farhad; Bazmani, Ahad; Momeni, Mohammad; Ravary, Ali; Kazemi Arababadi, Mohammad; Khalilian, Ali Reza

    2014-10-01

    Several lines of evidence approve that innate and adaptive immunity play key roles in the defense against visceral leishmaniasis (VL). The polymorphism within the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene alters its expression. The main aim of this study was to evaluate the polymorphism within the +49 position of the CTLA-4 gene of Iranian patients with VL in comparison with healthy controls. In this cross-sectional study, 88 patients with clinical presentations of VL, who were seropositive for Leishmania (group 1), 86 patients without clinical presentations but seropositive (group 2), and 115 healthy controls (group 3) were assessed with respect to the CTLA-4 +49A/G polymorphism, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The anti-Leishmania antibody titration was evaluated using an immunofluorescence method. Our results indicated that both CTLA-4 +49A/G polymorphisms were significantly associated with VL. According to the results, the polymorphisms within the +49 position of CTLA-4 can be associated with VL and may be considered as risk factors for the disease.

  8. Sero-prevalence of visceral leishmaniasis (VL among dogs in VL endemic areas of Mymensingh district, Bangladesh

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    Ariful Islam

    2017-09-01

    Full Text Available Objective: The present study was conducted to determine the sero-prevalence of canine visceral leishmaniasis (VL among street and owned dogs at Trishal Upazila of Mymensingh district, Bangladesh. Material and methods: Blood was collected asceptically from targeted dogs and serum was separated out using standard centrifigation method. The rK39-antigen-based dipstick test was used to detect anti-leishmania antibodies in serum. Results: The study revealed that 35% of the dogs in the study area were sero-positive for L. donovani. Living status of the dogs (street or owned was a potential risk factor and sero-prevalence was significantly higher in free roaming street dogs (P=0.009 and dogs with skin lesions and enlarged lymph nodes (P<0.05. The female and adult dogs were more susceptible. Conclusion: VL is an important zoonotic disease wich is transmissible to humans by the bite of phlebotomine sand fly. Dogs are the main reservoir. The higher sero-prevalence of VL indicates the potential rule of dogs to maintain the zoonosis wich need to be explored more specifically by isolation and typing of the parasite. [J Adv Vet Anim Res 2017; 4(3.000: 241-248

  9. 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.

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

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

    2016-01-01

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

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

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    Bhunia, Gouri Sankar; Kesari, Shreekant; Chatterjee, Nandini; Pal, Dilip Kumar; Kumar, Vijay; Ranjan, Alok; Das, Pradeep

    2011-05-01

    The role of the distribution of inland water bodies with respect to the transmission of visceral leishmaniasis (VL) and its dominant vector, Phlebotomous argentipes, has been studied at the regional scale in Bihar, eastern India. The Landsat TM sensor multispectral scanning radiometer, with a spatial resolution of 30 m in the visible, reflective-infrared and shortwave-infrared (SWIR) bands, was used to identify water bodies using the normalized differential pond index (NDPI) calculated as follows: (Green - SWIR I)/(Green + SWIR I). Nearest neighbour and grid square statistics were used to delineate spatial patterns and distribution of the sandfly vector and the disease it transmits. The female P. argentipes sandfly was found to be associated with the distance from open water and particularly abundant near non-perennial river banks (68.4%; P water source (χ(2) = 26.3; P distribution of VL is clustered around non-perennial riverbanks, while the pattern is slightly random around the perennial river banks. The grid square technique illustrate that the spatial distribution of the disease has a much stronger correlation with lower density of open waters surfaces as well as with sandfly densities (χ(2) = 26.0; P water presence poses a risk for VL by offering suitable breeding sites for P. argentipes, a fact that should be taken into account when attempting to control disease transmission.

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

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    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). Copyright © 2011 Elsevier B.V. All rights reserved.

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

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    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.

  14. Serum and tissue nitrate levels in murine visceral leishmaniasis correlate with parasite load but not with host protection.

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    Bories, C; Scherman, E; Bories, P N

    1997-01-01

    Nitrate levels were measured in serum and in organs from Lshs BALB/c and Lshr C3H/HeN mice during the acute phase (30 d) of infection by Leishmania donovani strain LV9. Serum nitrate levels increased rapidly in BALB/c mice from a baseline level (17 +/- 4 mumol/L) to a plateau (504 +/- 129 mumol/L) at 24 d and correlated with parasite loads in the liver (r = 0.817, P HeN mice, from 31 +/- 5 mumol/L to 86 +/- 5 mumol/L at 20 d. Liver nitrate content did not differ significantly between infected and control mice (1093 +/- 83 vs. 867 +/- 104 nmol), whereas the former had a higher spleen nitrate content (145 +/- 22 vs. 40 +/- 2 nmol, P HeN strain during the acute stage of infection by L. donovani. Tissue NO overproduction in organs infected by L. donovani was related to the progression of parasitic disease and contributed to high nitrate serum levels. It would be very interesting to extend this investigation to human disease with the aim of evaluating serum nitrate as a marker of parasite load in the follow-up of patients suffering from visceral leishmaniasis.

  15. 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.

  16. Leishmania specific CD4 T cells release IFNγ that limits parasite replication in patients with visceral leishmaniasis.

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    Rajiv Kumar

    2014-10-01

    Full Text Available Visceral leishmaniasis (VL is associated with increased circulating levels of multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNγ, and TNFα, and elevated expression of IFNγ mRNA in lesional tissue such as the spleen and bone marrow. However, an immunological feature of VL patients is that their peripheral blood mononuclear cells (PBMCs typically fail to respond to stimulation with leishmanial antigen. Unexpectedly, it was recently shown that Leishmania specific IFNγ, can readily be detected when a whole blood stimulation assay (WBA is used. We sought to define the conditions that permit whole blood cells to respond to antigen stimulation, and clarify the biological role of the IFNγ found to be released by cells from VL patients. CD4+ T cells were found to be crucial for and the main source of the IFNγ production in Leishmania stimulated whole blood (WB cultures. Complement, antibodies and red blood cells present in whole blood do not play a significant role in the IFNγ response. The IFNγ production was reduced by blockade of human leukocyte antigen (HLA-DR, indicating that the response to leishmanial antigens observed in WB of active VL patients is a classical HLA- T cell receptor (TCR driven reaction. Most importantly, blockade of IFNγ in ex-vivo splenic aspirate cultures demonstrated that despite the progressive nature of their disease, the endogenous IFNγ produced in patients with active VL serves to limit parasite growth.

  17. Immunogenicity and efficacy of single antigen Gp63, polytope and polytopeHSP70 DNA vaccines against visceral Leishmaniasis in experimental mouse model.

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    Rakhee Sachdeva

    Full Text Available Polytope approach of genetic immunization is a promising strategy for the prevention of infectious disease as it is capable of generating effective cell mediated immunity by delivering the T cell epitopes assembled in series. Leishmaniasis is a significant world wide health problem for which no vaccine exists. In this study we have compared immunogenicity and efficacy of three types of DNA vaccines: single antigen Gp63 (Gp63/pcDNA, polytope (Poly/pcDNA and Polytope fused with hsp70 (Poly/hsp/pcDNA against visceral leishmaniasis in susceptible BALB/c mice. Mice vaccinated with these plasmids generated strong Th1 immune response as seen by dominating IFN-gamma over IL-10 cytokine. Interestingly, cytotoxic responses generated by polytope DNA plasmid fused with hsp70 of Leishmania donovani were significantly higher when compared to polytope and single antigen Gp63 vaccine. Challenge studies revealed that the parasite load in liver and spleen was significantly lower with Poly/hsp/pcDNA vaccination compared to other vaccines. Therefore, our study indicates that polytope DNA vaccine is a feasible, practical and effective approach for visceral leishmaniasis.

  18. Immunogenicity and efficacy of single antigen Gp63, polytope and polytopeHSP70 DNA vaccines against visceral Leishmaniasis in experimental mouse model.

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    Sachdeva, Rakhee; Banerjea, Akhil C; Malla, Nancy; Dubey, Mohan Lal

    2009-12-02

    Polytope approach of genetic immunization is a promising strategy for the prevention of infectious disease as it is capable of generating effective cell mediated immunity by delivering the T cell epitopes assembled in series. Leishmaniasis is a significant world wide health problem for which no vaccine exists. In this study we have compared immunogenicity and efficacy of three types of DNA vaccines: single antigen Gp63 (Gp63/pcDNA), polytope (Poly/pcDNA) and Polytope fused with hsp70 (Poly/hsp/pcDNA) against visceral leishmaniasis in susceptible BALB/c mice. Mice vaccinated with these plasmids generated strong Th1 immune response as seen by dominating IFN-gamma over IL-10 cytokine. Interestingly, cytotoxic responses generated by polytope DNA plasmid fused with hsp70 of Leishmania donovani were significantly higher when compared to polytope and single antigen Gp63 vaccine. Challenge studies revealed that the parasite load in liver and spleen was significantly lower with Poly/hsp/pcDNA vaccination compared to other vaccines. Therefore, our study indicates that polytope DNA vaccine is a feasible, practical and effective approach for visceral leishmaniasis.

  19. Significance of persistence of antibodies against Leishmania infantum in Sicilian patients affected by acute visceral leishmaniasis.

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    Mansueto, Pasquale; Pepe, Ilenia; Seidita, Aurelio; Scozzari, Francesca; Vitale, Giustina; Arcoleo, Francesco; Elvira, Inglese; Cillari, Enrico; Rini, Giovam Battista; Napoli, Nicola; Di Rosa, Salvatore; Mansueto, Serafino; Di Fede, Gaetana

    2012-06-01

    The background of this article is as follows: Few data are available about the persistence of serum-specific IgG antibodies to L. infantum after acute VL. The objective of this article is to evaluate the persistence of antibodies against L. infantum in patients healed from acute VL, and the kinetic of the same antibodies observed in 2 cases of VL relapse and 2 cases of resistance to therapy. The methods which we used to obtain our objective are the following: 55 apparently immunocompetent, HIV-negative patients were examined for antibodies to L. infantum by IFAT over 14 years period, and we got the following results: Serum-specific IgG antibodies titers decrease slowly, but constantly. In the patients with a diagnosis of VL relapse, the kinetic of antibodies was characterized by an initial reduction, and a subsequent antibody levels rapidly increase, while in the patients with a clinical and parasitological diagnosis of VL not responding to specific therapy, we demonstrated persistent high level of antibodies to L. infantum. Finally, we conclude that specific antibodies to L. infantum might persist for many years, and decrease slowly, but steadily. The persistence of these specific antibodies is not related to poor therapeutic response or prognosis, but an acute increase in their levels might be a sentinel of a VL relapse, while persistence of high antibody levels could suggest a resistance to therapy.

  20. 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

  1. Evidence That Lipopolisaccharide May Contribute to the Cytokine Storm and Cellular Activation in Patients with Visceral Leishmaniasis

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    Santos-Oliveira, Joanna R.; Regis, Eduardo G.; Leal, Cássia R. B.; Cunha, Rivaldo V.; Bozza, Patrícia T.; Da-Cruz, Alda M.

    2011-01-01

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

  2. 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

  3. Recombinant NAD-dependent SIR-2 protein of Leishmania donovani: immunobiochemical characterization as a potential vaccine against visceral leishmaniasis.

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    Baharia, Rajendra K; Tandon, Rati; Sharma, Tanuj; Suthar, Manish K; Das, Sanchita; Siddiqi, Mohammad Imran; Saxena, Jitendra Kumar; Sundar, Shaym; Sunder, Shyam; Dube, Anuradha

    2015-03-01

    The development of a vaccine conferring long-lasting immunity remains a challenge against visceral leishmaniasis (VL). Immunoproteomic characterization of Leishmania donovani proteins led to the identification of a novel protein NAD+-dependent Silent Information regulatory-2 (SIR2 family or sirtuin) protein (LdSir2RP) as one of the potent immunostimulatory proteins. Proteins of the SIR2 family are characterized by a conserved catalytic domain that exerts unique NAD-dependent deacetylase activity. In the present study, an immunobiochemical characterization of LdSir2RP and further evaluation of its immunogenicity and prophylactic potential was done to assess for its possible involvement as a vaccine candidate against leishmaniasis. LdSir2RP was successfully cloned, expressed and purified. The gene was present as a monomeric protein of ~45 kDa and further established by the crosslinking experiment. rLdSir2RP shown cytosolic localization in L. donovani and demonstrating NAD+-dependent deacetylase activity. Bioinformatic analysis also confirmed that LdSir2RP protein has NAD binding domain. The rLdSir2RP was further assessed for its cellular response by lymphoproliferative assay and cytokine ELISA in cured Leishmania patients and hamsters (Mesocricetus auratus) in comparison to soluble Leishmania antigen and it was observed to stimulate the production of IFN-γ, IL-12 and TNF-α significantly but not the IL-4 and IL-10. The naïve hamsters when vaccinated with rLdSir2RP alongwith BCG resisted the L. donovani challenge to the tune of ~75% and generated strong IL-12 and IFN-γ mediated Th1 type immune response thereof. The efficacy was further supported by remarkable increase in IgG2 antibody level which is indicative of Th1 type of protective response. Further, with a possible implication in vaccine design against VL, identification of potential T-cell epitopes of rLdSir2RP was done using computational approach. The immunobiochemical characterization strongly suggest the

  4. Burden of visceral leishmaniasis in villages of eastern Gedaref State, Sudan: an exhaustive cross-sectional survey.

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    Yolanda Kathrin Mueller

    Full Text Available BACKGROUND: Since December 2009, Médecins Sans Frontières has diagnosed and treated patients with visceral leishmaniasis (VL in Tabarak Allah Hospital, eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was conducted to estimate the VL incidence in villages around Tabarak Allah. METHODS: Between the 5(th of May and the 17(th of June 2011, we conducted an exhaustive door-to-door survey in 45 villages of Al-Gureisha locality. Deaths were investigated by verbal autopsies. All individuals with (i fever of at least two weeks, (ii VL diagnosed and treated in the previous year, and (iii clinical suspicion of post-kala-azar dermal leishmaniasis (PKDL were referred to medical teams for case ascertainment. A new case of VL was a clinical suspect with a positive rk39 rapid test or direct agglutination test (DAT. RESULTS: In the 45 villages screened, 17,702 households were interviewed, for a population of 94,369 inhabitants. The crude mortality rate over the mean recall period of 409 days was 0.13/10'000 people per day. VL was a possible or probable cause for 19% of all deaths. The VL-specific mortality rate was estimated at 0.9/1000 per year. The medical teams examined 551 individuals referred for a history of fever of at least two weeks. Out of these, 16 were diagnosed with primary VL. The overall incidence of VL over the past year was 7.0/1000 persons per year, or 7.9/1000 per year when deaths possibly or probably due to VL were included. Overall, 12.5% (11,943/95,609 of the population reported a past VL treatment episode. DISCUSSION AND CONCLUSION: VL represents a significant health burden in eastern Gedaref State. Active VL case detection had a very low yield in this specific setting with adequate access to care and may not be the priority intervention to enhance control in similar contexts.

  5. High frequency of visceral leishmaniasis in dogs under veterinary clinical care in an intense transmission area in the state of Tocantins, Brazil

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    Helcileia Dias Santos

    Full Text Available ABSTRACT: A direct search for parasites were used as the diagnostic test to determine the frequency of Leishmania spp. infection in dogs ( Canis lupus familiaris under veterinary clinical care in the city of Araguaína, Tocantins, Brazil. For this approach, lymph node cell samples were collected using needle aspiration from 649 dogs of different breeds and ages. Two hundred and sixty four (40.7% dogs tested positive for amastigote forms of Leishmania spp. Furthermore, 202 (76.5% dogs that tested positive showed some clinical sign of disease, while 62 (28.4% dogs were asymptomatic. Dogs <2 years old or those that lived alongside poultry species in peri-domicile areas had a greater chance of infection (P<0.05. Our results revealed the importance of frequently monitoring leishmaniasis in dogs, and the need to train veterinary professionals who work in high-transmission areas on the clinical diagnosis of canine visceral leishmaniasis.

  6. 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.

  7. 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

    2012-01-01

    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. PMID:22301630

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

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    Antonio Carlos Toledo Jr.

    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.

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

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    Bhowmick Sudipta

    2010-06-01

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

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

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    Ravindran, Rajesh; Bhowmick, Sudipta; Das, Amrita; Ali, Nahid

    2010-06-24

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

  11. A case-control study of microenvironmental risk factors for urban visceral leishmaniasis in a large city in Brazil, 1999-2000 Estudio de casos y controles sobre factores microambientales de riesgo de leishmaniasis visceral urbana en una gran urbe de Brasil, 1999-2000

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    Claudia Di Lorenzo Oliveira

    2006-12-01

    Full Text Available OBJECTIVES: We investigated potential microenvironmental risk factors for visceral leishmaniasis in urban and suburban areas, and developed risk scores to characterize the household and the neighborhood. These scores may be useful to identify microenvironments within cities that place residents at greater risk of visceral leishmaniasis. METHODS: In this case-control study, cases were all persons with visceral leishmaniasis reported from July 1999 through December 2000 in the Belo Horizonte metropolitan area, Brazil. Two kinds of controls-neighborhood and hospital-were used. Cases and controls were matched by age (±2 years. We developed four scores to characterize the microenvironment (indoor, outdoor, animal indoor, and animal outdoor, and also considered the level of urbanization of the area. RESULTS: A total of 106 neighborhood controls and 60 hospital controls were identified for 109 cases. Among the cases, 69 (63.3% were men and 40 (36.7% were women. Most cases were under 15 years old (64.2%, and 39 (35.8% were 15 years old or more. The outdoor score [odds ratio (OR = 1.49; 95% confidence interval (CI = 1.03-2.14] and animal outdoor scores (OR = 1.79[95% CI 1.21-2.65] were significantly associated with the odds of visceral leishmaniasis in our sample. We also found a significant interaction between sex and age. Compared to females 15 years old or more, males 15 years old or more were more likely to have visceral leishmaniasis (OR = 7.02[95% CI 2.20-22.20]. CONCLUSIONS: Animals in the neighborhood were associated with a greater odds of visceral leishmaniasis. Cases were more likely than controls to live in transitional or rural areas, although this difference was not statistically significant, possibly because of the small sample size.OBJETIVOS: Se investigaron los posibles factores microambientales de riesgo de leishmaniasis visceral en áreas urbanas y suburbanas y se elaboraron sistemas de puntuación del riesgo para caracterizar los

  12. Avaliação do nível de conhecimento e de atitudes preventivas da população sobre a leishmaniose visceral em Belo Horizonte, Minas Gerais, Brasil Assessment of knowledge and preventive attitudes concerning visceral leishmaniasis in Belo Horizonte, Minas Gerais State, Brazil

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    Bárbara Kellen Antunes Borges

    2008-04-01

    Full Text Available Objetivou-se avaliar o nível de conhecimento e algumas atitudes preventivas em relação à leishmaniose visceral em Belo Horizonte, Minas Gerais, Brasil, em 2006. Foi feito um estudo de caso-controle, com visitas domiciliares e questionário semi-estrurado. Comparou-se dois grupos: (1 82 casos humanos de leishmaniose visceral ocorridos em 2004 e (2 164 controles, constituídos por vizinhos dos casos. A leishmaniose visceral acometeu mais em crianças, com aumento do risco de contrair leishmaniose visceral de 109,77 vezes para menores de dez anos. O homem demonstrou ter 2,57 vezes mais chances de adoecer que a mulher. A escolaridade da população mostrou-se baixa (68,3% não completaram o ensino médio. Cinqüenta por cento dos casos desconheciam-na quando foram infectados e apenas 1,2% conhecia o vetor. Conhecer algo sobre a leishmaniose visceral minimizou o risco de adoecer em 2,24 vezes. Quanto às atitudes de proteção, o risco de se contrair leishmaniose visceral diminui em 1,94 vez para pessoas que mantêm limpos os domicílios ou que levam o cão ao veterinário. Em Belo Horizonte, o conhecimento da população perante a leishmaniose visceral é superficial e as atitudes preventivas inespecíficas.The main objective of this study was to evaluate knowledge concerning visceral leishmaniasis and attitudes used to prevent the disease in Belo Horizonte, Minas Gerais State, Brazil, in 2006. A case-control study was conducted, with home visits and a questionnaire. The odds ratio was calculated, comparing 82 cases of human visceral leishmaniasis in 2004 and 164 controls (neighbors of cases. The disease was more frequent in children (OR = 109.77. Visceral leishmaniasis was 2.57 times more likely in males than in females. Overall schooling level was low (68.3% of subjects had not completed secondary school. Half of the cases did not know what visceral leishmaniasis was, and only 1.2% could identify the vector. Having basic knowledge of visceral

  13. 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.

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

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    Cláudia Di Lorenzo Oliveira

    2001-10-01

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

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

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

    2016-08-01

    It is well known that a patient in clinical remission of visceral leishmaniasis (VL) remains immune to reinfection, which provides a rationale for the feasibility of a vaccine against this deadly disease. In earlier studies, observation of significant cellular responses in treated Leishmania patients as well as in hamsters against leishmanial antigens from different fractions led to its further proteomic characterization, wherein S-adenosyl-L-homocysteine hydrolase (AdoHcy) was identified as a helper type 1 (Th1) stimulatory protein. The present study includes immunological characterization of this protein, its cellular responses [lymphoproliferation, nitric oxide (NO) production and cytokine responses] in treated Leishmania-infected hamsters and patients as well as prophylactic efficacy against Leishmania challenge in hamsters and the immune responses generated thereof. Significantly higher cellular responses were noticed against recombinant L. donovani S-adenosyl-L-homocysteine hydrolase (rLdAdoHcy) compared to soluble L. donovani antigen in treated samples. Moreover, stimulation of peripheral blood mononuclear cells with rLdAdoHcy up-regulated the levels of interferon (IFN)-γ, interleukin (IL)-12 and down-regulated IL-10. Furthermore, vaccination with rLdAdoHcy generated perceptible delayed-type hypersensitivity response and exerted considerably good prophylactic efficacy (∼70% inhibition) against L. donovani challenge. The efficacy was confirmed by the increased expression levels of inducible NO synthase and Th1-type cytokines, IFN-γ and IL-12 and down-regulation of IL-4, IL-10 and transforming growth factor (TGF)-β. The results indicate the potentiality of rLdAdoHcy protein as a suitable vaccine candidate against VL. © 2016 British Society for Immunology.

  16. 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

  17. The Genetic Structure of Leishmania infantum Populations in Brazil and Its Possible Association with the Transmission Cycle of Visceral Leishmaniasis

    Science.gov (United States)

    Ferreira, Gabriel Eduardo Melim; dos Santos, Barbara Neves; Dorval, Maria Elizabeth Cavalheiros; Ramos, Tereza Pompilio Bastos; Porrozzi, Renato; Peixoto, Alexandre Afranio; Cupolillo, Elisa

    2012-01-01

    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. PMID:22606248

  18. Subtractive phage display selection from canine visceral leishmaniasis identifies novel epitopes that mimic Leishmania infantum antigens with potential serodiagnosis applications.

    Science.gov (United States)

    Costa, Lourena E; Lima, Mayara I S; Chávez-Fumagalli, Miguel A; Menezes-Souza, Daniel; Martins, Vivian T; Duarte, Mariana C; Lage, Paula S; Lopes, Eliane G P; Lage, Daniela P; Ribeiro, Tatiana G; Andrade, Pedro H R; de Magalhães-Soares, Danielle F; Soto, Manuel; Tavares, Carlos A P; Goulart, Luiz R; Coelho, Eduardo A F

    2014-01-01

    Visceral leishmaniasis (VL) is a zoonotic disease that is endemic to Brazil, where dogs are the main domestic parasite reservoirs, and the percentages of infected dogs living in regions where canine VL (CVL) is endemic have ranged from 10% to 62%. Despite technological advances, some problems have been reported with CVL serodiagnosis. The present study describes a sequential subtractive selection through phage display technology from polyclonal antibodies of negative and positive sera that resulted in the identification of potential bacteriophage-fused peptides that were highly sensitive and specific to antibodies of CVL. A negative selection was performed in which phage clones were adhered to purified IgGs from healthy and Trypanosoma cruzi-infected dogs to eliminate cross-reactive phages. The remaining supernatant nonadhered phages were submitted to positive selection against IgG from the blood serum of dogs that were infected with Leishmania infantum. Phage clones that adhered to purified IgGs from the CVL-infected serum samples were selected. Eighteen clones were identified and their reactivities tested by a phage enzyme-linked immunosorbent assay (phage-ELISA) against the serum samples from infected dogs (n = 31) compared to those from vaccinated dogs (n = 21), experimentally infected dogs with cross-reactive parasites (n = 23), and healthy controls (n = 17). Eight clones presented sensitivity, specificity, and positive and negative predictive values of 100%, and they showed no cross-reactivity with T. cruzi- or Ehrlichia canis-infected dogs or with dogs vaccinated with two different commercial CVL vaccines in Brazil. Our study identified eight mimotopes of L. infantum antigens with 100% accuracy for CVL serodiagnosis. The use of these mimotopes by phage-ELISA proved to be an excellent assay that was reproducible, simple, fast, and inexpensive, and it can be applied in CVL-monitoring programs.

  19. 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 ery