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Showing papers on "Visceral leishmaniasis published in 2007"


Journal ArticleDOI
TL;DR: Millefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphoteric in B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies.
Abstract: Visceral leishmaniasis (VL) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. Poor and neglected populations in East Africa and the Indian sub-continent are particularly affected. Early and accurate diagnosis and treatment remain key components of VL control. In addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. Miltefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphotericin B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies. New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients.

1,463 citations


Journal ArticleDOI
TL;DR: A randomized, controlled, phase 3 open-label study comparing paromomycin, an aminoglycoside, with amphotericin B, the present standard of care for the treatment of visceral leishmaniasis in Bihar, India, showed parmomycin was shown to be noninferior to amphoteric in B.
Abstract: A b s t r ac t P<0.001); and in patients receiving amphotericin B, as compared with those receiving paromomycin, nephrotoxicity (4% vs. 0, P<0.001), fevers (57% vs. 3%), rigors (24% vs. 0, P<0.001), and vomiting (10% vs. <1%, P<0.001). Conclusions Paromomycin was shown to be noninferior to amphotericin B for the treatment of visceral leishmaniasis in India. (ClinicalTrials.gov number, NCT00216346.)

411 citations


Journal ArticleDOI
TL;DR: The studies with relevance to immune responses in human VL are reviewed and the central role that IL-10 might have in the pathogenesis of VL and as a target for immune-based therapy is highlighted.

333 citations


Journal ArticleDOI
TL;DR: The results did not point to an important role for natural CD4+CD25+ (Foxp3high) T reg cells in human VL, but elevated levels of IL-10 in VL plasma significantly enhanced the growth of L. donovani amastigotes in human macrophages.
Abstract: Visceral leishmaniasis (VL) is a life-threatening disease characterized by uncontrolled parasitization of the spleen, liver, and bone marrow. Interleukin (IL)-10 has been implicated in the suppression of host immunity in human VL based on the elevated levels of IL-10 observed in plasma and lesional tissue, and its role in preventing clearance of Leishmania donovani in murine models of VL. The aim of this study was to identify the cellular source of IL-10 in human VL and determine if CD4+CD25+ (Foxp3high) regulatory T (T reg) cells are associated with active disease. We analyzed surface marker and gene expression in peripheral blood mononuclear cells and splenic aspirates from Indian VL patients before and 3–4 wk after treatment with Amphotericin B. The results did not point to an important role for natural CD4+CD25+ (Foxp3high) T reg cells in human VL. They did not accumulate in and were not a major source of IL-10 in the spleen, and their removal did not rescue antigen-specific interferon γ responses. In contrast, splenic T cells depleted of CD25+ cells expressed the highest levels of IL-10 mRNA and were the predominant lymphocyte population in the VL spleen. The elevated levels of IL-10 in VL plasma significantly enhanced the growth of L. donovani amastigotes in human macrophages. The data implicate IL-10–producing CD25−Foxp3− T cells in the pathogenesis of human VL.

310 citations


01 Jan 2007
TL;DR: The most severe form of leishmanial disease, kala-azar, is a chronic infectious disease characterized by fever, enlargement of the spleen and liver, weight loss, anemia, and leucopenia as mentioned in this paper.
Abstract: Visceral leishmaniasis (VL), or kala-azar, the most severe form of leishmanial disease, is a chronic infectious disease characterized by fever, enlargement of the spleen and liver, weight loss, anemia, and leucopenia. If left untreated, VL is generally fatal. Most cases of kala-azar occur in India, Sudan, Nepal, and Bangladesh, where it is caused by the trans mission of

289 citations


Journal ArticleDOI
TL;DR: Insightful insights derived from recent research indicate that not dogs but humans are probably the most important domestic reservoirs of L. (L.) infantum and L. braziliensis, and the role of dogs as reservoirs of Leishmania parasites is reviewed.

270 citations


Journal ArticleDOI
TL;DR: The present review describes the current understanding of different drugs against leishmaniasis, their chemistry, mode of action and the mechanism of resistance in the parasite.
Abstract: Leishmaniasis is a parasitic disease caused by hemoflagellate, Leishmania spp. The parasite is transmitted by the bite of an infected female phlebotomine sandfly. The disease is prevalent throughout the world and in at least 88 countries. Nearly 25 compounds are reported to have anti-leishmanial effects but not all are in use. The pentavalent antimony compounds have remained mainstay for nearly 75 years. Pentavalent antimony is a prodrug that is reduced by glutathione to active trivalent species catalyzed by thiol-dependent-reductase. However, emergence of resistance led to the use of other compounds -amphotericin B, pentamidine, paromomycin, allopurinol etc. Amphotericin B, an antifungal macrolide polyene is characterized by the hydrophilic polyhydroxyl and hydrophobic polyene faces on it long axis. Presently, it is the only drug with highest cure rate. It acts on membrane sterols resulting in parasite cell lysis. Its lipid formulations have been developed to minimize side effects. Other anti-fungals like ketoconazole, fluconazole and terbinafine are found less effective. Recently, anticancer alkylphosphocholines have been found most effective oral compounds. These act as membrane synthetic ether-lipid analogues, and consist of alkyl chains in the lipid portions. Most promising of these are miltefosine (hexadecylphosphocholine), edelfosine (ET-18-OCH3) and ilmofosine (BM 41.440). However, the recent focus has been on identifying newer therapeutic targets in the parasite such as DNA topoisomerases. The present review describes the current understanding of different drugs against leishmaniasis, their chemistry, mode of action and the mechanism of resistance in the parasite. Future perspectives in the area of new anti-leishmanial drug targets are also enumerated. However, due to the vastness of the topic main emphasis is given on visceral leishmaniasis.

261 citations


Journal ArticleDOI
TL;DR: Intralesional or systemic antimonials are the gold standard for the treatment of visceral leishmaniasis, however, other therapeutic options appear promising, and Liposomal amphotericin B could be an alternative to antimony in south American cutaneous leish maniasis with mucosal involvement.

245 citations


Journal ArticleDOI
TL;DR: This study supports the use of miltefosine in an outpatient setting in an area where VL is endemic, and reports a cure rate similar to the 94% cure rate in hospitalized patients.
Abstract: Visceral leishmaniasis (VL) is a major public health problem in Bihar accounting for 90% of all cases in India. Development of high levels of resistance to various existing drugs necessitated the search for alternative orally administered drugs. Hospital-based studies have shown that oral miltefosine is a highly effective treatment for VL both in adults and in children. An open single-arm trial was designed to investigate the feasibility of treatment of VL patients with miltefosine in field conditions in 13 centers in Bihar. The phase 4 study was conducted among 1132 adult and pediatric VL patients. Compliance was good with 1084 (95.5%) patients completing the full 28-day treatment course. Nine hundred and seventy-one (85.8%) patients returned for the final cure assessment at 6 months after treatment. The final cure rate was 82% by intention to treat analysis and 95% by per protocol analysis (similar to the 94% cure rate in hospitalized patients). Treatment-related adverse events of common toxicity criteria grade 3 occurred in ~3% of patients including gastrointestinal toxicity and rise in aspertate amino transferase alanine amino transferase or serum creatinine levels similar to previous clinical experience. This study supports the use of miltefosine in an outpatient setting in an area where VL is endemic. (authors)

229 citations


Journal ArticleDOI
TL;DR: A fine immunological balance determines responses that effectively promote parasite clearance in the liver and those that promote pathology in the spleen, and future investigation aims to separate these responses to offer further means of parasite control in chronically infected VL patients.
Abstract: Experimental visceral leishmaniasis (VL) caused by infection with Leishmania donovani results in the development of organspecific immunity in the two main target tissues of infection, the spleen and the liver. The liver is the site of an acute resolving infection associated with the development of inflammatory granulomas around infected Kupffer cells, and resistance to reinfection. Paradoxically, the spleen is an initial site for the generation of cell-mediated immune responses, but ultimately becomes a site of parasite persistence with associated immunopathological changes. These include splenomegaly and a breakdown in tissue architecture that is postulated to contribute to the immunocompromized status of the host. The progressive development of splenic pathology is largely associated with high levels of TNF and interleukin (IL)-10. Follicular dendritic cell (DC) networks are lost, whereas TNF mediates the destruction of marginal zone macrophages and gp38(+) stromal cells, and IL-10 promotes impaired DC migration into T-cell areas with consequent ineffective T-cell priming. Splenic stromal cell function is also altered, promoting the selective development of IL-10-producing DC with immunoregulatory properties. Ultimately, a fine immunological balance determines responses that effectively promote parasite clearance in the liver and those that promote pathology in the spleen, and future investigation aims to separate these responses to offer further means of parasite control in chronically infected VL patients.

223 citations


Journal ArticleDOI
TL;DR: The Leish-111f+MPL-SE product reported here is the first defined vaccine for leishmaniasis in human clinical trials and has completed phase 1 and 2 safety and immunogenicity testing in normal, healthy human subjects.
Abstract: The Leishmania-derived recombinant polyprotein Leish-111f or its three component proteins, thiol-specific antioxidant (TSA), Leishmania major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF), have previously been demonstrated to be efficacious against cutaneous or mucosal leishmaniasis in mice, nonhuman primates, and humans. In this study we demonstrate that Leish-111f is also a vaccine antigen candidate against visceral leishmaniasis (VL) caused by Leishmania infantum. We evaluated the immune response and protection induced by Leish-111f formulated with monophosphoryl lipid A in a stable emulsion (Leish-111f+MPL-SE) and demonstrated that mice developed strong humoral and T-cell responses to the vaccine antigen. Analysis of the cellular immune responses of immunized, uninfected mice demonstrated that the vaccine induced a significant increase in CD4+ T cells producing gamma interferon, interleukin 2, and tumor necrosis factor cytokines, indicating a Th1-type immune response. Experimental infection of immunized mice and hamsters demonstrated that Leish-111f+MPL-SE induced significant protection against L. infantum infection, with reductions in parasite loads of 99.6%, a level of protection greater than that reported for other vaccine candidates in animal models of VL. Taken together, our results suggest that this vaccine represents a good candidate for use against several Leishmania species. The Leish-111f+MPL-SE product we report here is the first defined vaccine for leishmaniasis in human clinical trials and has completed phase 1 and 2 safety and immunogenicity testing in normal, healthy human subjects.

Journal Article
TL;DR: Miltefosine has great potential for improving access to treatment and overall control of VL and will be critical in the VL elimination campaign in the Indian subcontinent, but must be safeguarded or will be lost if misused.
Abstract: Visceral leishmaniasis (VL) is a life-threatening disease. Traditional treatment with pentavalent antimony injections has become ineffective in the area with the world’s highest prevalence of disease (North Bihar, India) and is becoming less effective elsewhere as well. A replacement is needed, best if it can be given to more patients outside the hospital. Miltefosine is the first oral drug registered for VL. Given daily under medical supervision for 4 weeks, it cures 94% of patients (both children and adults) and is reasonably safe. Miltefosine has great potential for improving access to treatment and overall control of VL and will be critical in the VL elimination campaign in the Indian subcontinent, but must be safeguarded or will be lost if misused. Its main limitations are adherence (and hence potential for selection of drug resistant parasites) and teratogenicity (pregnancy must be avoided during treatment and the following two months). This calls for responsible deployment, setting in place mechanisms to protect female patients in child-bearing age, monitoring effects and optimizing adherence in real-life conditions through directly observed therapy. One option to protect the useful life-span of miltefosine consists in shortening treatment duration by combining it with another drug.

Journal ArticleDOI
TL;DR: PCR assay is a highly sensitive and specific tool for the diagnosis of visceral leishmaniasis in both immunocompetent and Immunocompromised patients and can be reliably used for rapid parasite identification at the species level.
Abstract: Background To overcome some of the limitations of conventional microbiologic techniques, polymerase chain reaction (PCR)-based assays are proposed as useful tools for the diagnosis of visceral leishmaniasis. Patients and methods A comparative study using conventional microbiologic techniques (i.e., serologic testing, microscopic examination, and culture) and a Leishmania species-specific PCR assay, using peripheral blood and bone marrow aspirate samples as templates, was conducted during an 8-year period. The study cohort consisted of 594 Italian immunocompetent (adult and pediatric) and immunocompromised (adult) patients experiencing febrile syndromes associated with hematologic alterations and/or hepatosplenomegaly. Identification of the infecting protozoa at the species level was directly obtained by PCR of peripheral blood samples, followed by restriction fragment-length polymorphism analysis of the amplified products, and the results were compared with those of isoenzyme typing of Leishmania species strains from patients, which were isolated in vitro. Results Sixty-eight patients (11.4%) had a confirmed diagnosis of visceral leishmaniasis. Eleven cases were observed in human immunodeficiency virus (HIV)-uninfected adults, 20 cases were observed in HIV-infected adults, and the remaining 37 cases were diagnosed in HIV-uninfected children. In the diagnosis of primary visceral leishmaniasis, the sensitivities of the Leishmania species-specific PCR were 95.7% for bone marrow aspirate samples and 98.5% for peripheral blood samples versus sensitivities of 76.2%, 85.5%, and 90.2% for bone marrow aspirate isolation, serologic testing, and microscopic examination of bone marrow biopsy specimens, respectively. None of 229 healthy blood donors or 25 patients with imported malaria who were used as negative control subjects had PCR results positive for Leishmania species in peripheral blood samples (i.e., specificity of Leishmania species-specific PCR, 100%). PCR and restriction fragment-length polymorphism analysis for Leishmania species identification revealed 100% concordance with isoenzyme typing in the 19 patients for whom the latter data were available. Conclusions PCR assay is a highly sensitive and specific tool for the diagnosis of visceral leishmaniasis in both immunocompetent and immunocompromised patients and can be reliably used for rapid parasite identification at the species level.

Journal ArticleDOI
TL;DR: Vector and reservoir control is difficult due to the elusive nature of the vector and the diversity of the animal reservoir and a detailed knowledge of immune response to the parasite would help in designing prophylactic and therapeutic strategies against this infection.
Abstract: The leishmaniases are a group of diseases caused by protozoan parasites of the genus Leishmania. Various Leishmania species can cause human infection, producing a spectrum of clinical manifestations. It is estimated that 350 million people are at risk, with a global yearly incidence of 1-1.5 million for cutaneous and 500,000 for visceral leishmaniasis (VL). VL is a major cause of morbidity and mortality in East Africa and the Indian subcontinent. Coinfection with HIV enhances the risk of the disease. The only control measure currently available in India is case detection and treatment with antimonial drugs, which are expensive, not always available and cannot be self-administered. Newer drugs like oral miltefosine have not become widely available. Vector and reservoir control is difficult due to the elusive nature of the vector and the diversity of the animal reservoir. A detailed knowledge of immune response to the parasite would help in designing prophylactic and therapeutic strategies against this infection.


Journal ArticleDOI
TL;DR: A spectral pattern of disease progression where disease severity could be correlated inversely with lymphoproliferation and directly with TGF-β, IL-10, and Ab production is revealed, suggesting their probable immunosuppressive role in these disease forms.
Abstract: Visceral leishmaniasis (VL) or kala-azar is known to be associated with a mixed Th1-Th2 response, and effective host defense requires the induction of IFN-gamma and IL-12. We address the role of the differential decline of IL-10 and TGF-beta in response to sodium antimony gluconate (SAG) and amphotericin B (AmB), the therapeutic success of SAG and AmB in Indian VL, and the significance of IL-10 and TGF-beta in the development and progression of post-kazla-azar dermal leishmaniasis (PKDL). In the active disease, PBMC from VL patients showed suppressed Ag-specific lymphoproliferation, IFN-gamma and IL-12 production, and elevation of IL-10 and TGF-beta. Cure corresponded with an elevation in IFN-gamma and IL-12 production and down-regulation of IL-10 and TGF-beta. Both CD4(+) and CD8(+) T cells were involved in IFN-gamma and IL-10 production. Interestingly, the retention and maintenance of residual IL-10 and TGF-beta in some SAG-treated individuals and the elevation of IL-10 and TGF-beta in PKDL, a sequel to kala-azar, probably reflects the role of these cytokines in reactivation of the disease in the form of PKDL. Contrastingly, AmB treatment of VL resulted in negligible TGF-beta levels and absolute elimination of IL-10, reflecting the better therapeutic activity of AmB and its probable role in the recent decline in PKDL occurrences in India. Moreover, elucidation of immune responses in Indian PKDL patients revealed a spectral pattern of disease progression where disease severity could be correlated inversely with lymphoproliferation and directly with TGF-beta, IL-10, and Ab production. In addition, the enhancement of CD4(+)CD25(+) T cells in active VL, their decline at cure, and reactivation in PKDL suggest their probable immunosuppressive role in these disease forms.

Journal ArticleDOI
22 May 2007-Vaccine
TL;DR: The LiESAp-MDP vaccine induced a significant, long-lasting and strong protective effect against canine visceral leishmaniasis in the field, and was established by the results of their immune status.

Journal ArticleDOI
TL;DR: Data indicates that all three recombinant proteins must be used in parallel to detect essentially all infected dogs, and efforts should be made to develop a cheap and reliable serologic test based on epitope selection from these diagnostic markers for the sensitive detection of L. infantum-infected dogs.
Abstract: The diagnosis of visceral leishmaniasis remains difficult in rural areas where the disease is endemic, and serologic methods still need assessment, as they are not very sensitive for the detection of asymptomatic infectious dogs. Here we present data on the development of enzyme-linked immunosorbent assay (ELISA)-based methods for the detection of antibodies against recombinant leishmanial antigens (namely, the recombinant K26 [rK26] and rK39 antigens from Leishmania infantum and the rA2 protein from Leishmania donovani) in comparison to ELISAs employing crude soluble antigen (CSA). The assays utilized sera from known negative controls (n=25) and clinically asymptomatic (n=50) and symptomatic (n=50) dogs with confirmed L. infantum infections. Additional studies were also done using sera from animals harboring other infections (n=14) for the evaluation of cross-reactivity. Our study indicated that rK26 and rK39 used in ELISAs provided very high sensitivities for the detection of symptomatic dogs (94% and 100%, respectively), followed by CSA (88%) and rA2 (70%). Conversely, rA2 was more sensitive for asymptomatic dogs (88%) than rK39 and rK26 (both 66%) and CSA (30%). Some cross-reactivity in sera from dogs with other infections (Leishmania braziliensis and Leptospira interrogans) was identified, but the rA2 protein provided the greatest specificity (98%). Data further indicate that all three recombinant proteins must be used in parallel to detect essentially all infected dogs. Efforts should be made to develop a cheap and reliable serologic test based on epitope selection from these diagnostic markers for the sensitive detection of L. infantum-infected dogs.

Journal ArticleDOI
TL;DR: 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.

Journal ArticleDOI
TL;DR: The ability of PCR to diagnose VL and distinguish L. (L.) chagasi from other Leishmania species in domestic dogs and the importance of including PCR in diagnosis of Leishmaniases by differential diagnosis contributing to the surveillance and control of VL programs are shown.

Journal ArticleDOI
TL;DR: Results suggest that L. (L.) amazonensis is being transmitted in the peridomestic habitat and that this parasite is responsible for a clinical condition that is similar to visceral leishmaniasis caused by L. chagasi that is present in the same area.

Journal ArticleDOI
TL;DR: Evaluation of rapid diagnostic tests for confirmation of VL disease finds that PCR is usually highly sensitive for detection of leishmanial infection, but this does not mean PCR will be useful for the confirmation of acute Vl disease in patients in endemic areas, as many carriers of the infection in these areas will be PCRpositive without developing VL Disease.
Abstract: Visceral leishmaniasis (VL) is a severe infectious disease caused by a protozoan parasite: Leishmania donovani in East Africa and the Indian subcontinent and Leishmania infantum in Latin America and the Mediterranean basin. Not all leishmanial infections lead to overt clinical disease, but in those infected persons who do develop the disease, multiplication of the parasite in the reticulo-endothelial system causes prolonged fever, anaemia, hepatosplenomegaly and weight loss. VL is fatal if it is not adequately treated. The drugs currently used to treat VL can have severe side effects and the clinical presentation of VL is not sufficiently specific to guide treatment. Highly accurate (both sensitive and specific), cheap and simple rapid diagnostic tests (RDTs) are therefore crucial for case-management of VL. Early case detection followed by adequate treatment is also central to control of VL because, as yet, no vaccine is available and the long-term impact of vector control is unclear. Although the need for accurate VL diagnostics is obvious, innovation in this field has been slow. Since the 1980s, the main objective of VL diagnostics development has been to replace the direct demonstration of parasites in tissue smears, a technique that is invasive and requires considerable expertise, by a ‘field test’ that is more appropriate for use in a VL-endemic context. Several serological tests have been developed, but none are specific for VL disease as such, although they have proved useful in combination with a clinical case definition. New diagnostic tools are needed for more than just the confirmation of VL disease. No alternatives to parasitological methods are yet available to establish test of cure in treated VL patients. Clinicians do not have the tools to distinguish re-infection from relapse in cases of recurrence, and control programmes do not have validated assays for the surveillance of drug resistance in parasites. Furthermore, in the context of the VL elimination initiative, it would be desirable to have better markers of leishmanial infection at the population level. Any evaluation of a new diagnostic device should carefully identify its intended purpose. Too often developers and researchers confuse a device for the detection of leishmanial infection with a device for the confirmation of VL disease, and this is particularly the case for nucleic-acidbased assays. PCR is usually highly sensitive for detection of leishmanial infection, but this does not mean PCR will be useful for the confirmation of acute VL disease in patients in endemic areas, as many carriers of the infection in these areas will be PCRpositive without developing VL disease. This article will focus specifically on the evaluation of RDTs for confirmation of VL disease.

Journal ArticleDOI
TL;DR: It is proposed that the polarization to a high IFN-γ/low IL-10 ratio after challenge is a clear indicator of vaccine success and these mutants, which presented attenuated virulence, represent a good model to understand the correlatives of protection in visceral leishmaniasis.
Abstract: The ability to manipulate the Leishmania genome to create genetically modified parasites by introducing or eliminating genes is considered a powerful alternative for developing a new generation vaccine against leishmaniasis. Previously, we showed that the deletion of one allele of the Leishmania infantum silent information regulatory 2 (LiSIR2) locus was sufficient to dramatically affect amastigote axenic proliferation. Furthermore, LiSIR2 single knockout (LiSIR2(+/-)) amastigotes were unable to replicate in vitro inside macrophages. Because this L. infantum mutant persisted in BALB/c mice for up to 6 wk but failed to establish an infection, we tested its ability to provide protection toward a virulent L. infantum challenge. Strikingly, vaccination with a single i.p. injection of LiSIR2(+/-) single knockout elicits complete protection. Thus, vaccinated BALB/c mice showed a reversal of T cell anergy with specific anti-Leishmania cytotoxic activity and high levels of NO production. Moreover, vaccinated mice simultaneously generated specific anti-Leishmania IgG Ab subclasses suggestive of both type 1 and type 2 responses. A strong correlation was found between the elimination of the parasites and an increased Leishmania-specific IFN-gamma/IL-10 ratio. Therefore, we propose that the polarization to a high IFN-gamma/low IL-10 ratio after challenge is a clear indicator of vaccine success. Furthermore these mutants, which presented attenuated virulence, represent a good model to understand the correlatives of protection in visceral leishmaniasis.

Journal ArticleDOI
TL;DR: Findings indicate that visceral leishmaniasis transmission has become disseminated throughout the state of Mato Grosso, following migratory flows and the process of disorderly occupation of urban areas.
Abstract: An epidemic of visceral leishmaniasis began in 1998, in the Metropolitan Region of Cuiaba, 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 alone in areas with high incidence of human and canine cases suggests possible participation by this species in the transmission chain for visceral leishmaniasis in Mato Grosso.

Journal ArticleDOI
TL;DR: This study substantiates the usefulness of proteomics in characterizing a complex protein fraction (F2) map of soluble L. donovani promastigote antigen identified as Th1 stimulatory for its potential as vaccine targets against VL.
Abstract: Visceral leishmaniasis (VL) caused by Leishmania donovani is a major parasitic disease prevalent in endemic regions of Bihar in India. In the absence of good chemotherapeutic options, there is a need to develop an effective vaccine against VL which should be dependent on the generation of a T helper type 1 (Th1) immune response. We have shown that soluble proteins from promastigote of a new clinical isolate of L. donovani (2001) ranging from 68 to 97.4 kDa (F2 fraction), induce Th1 responses in the peripheral blood mononuclear cells of cured Leishmania patients and hamsters and also showed significant prophylactic potential. To understand the nature of F2 proteins, it was further characterized using 2-DE, MALDI-TOF and MALDI-TOF/TOF-MS. In all, 63 spots were cut from a CBB stained gel for analysis and data was retrieved for 52 spots. A total of 33 proteins were identified including six hypothetical/unknown proteins. Major immunostimulatory proteins were identified as elongation factor-2, p45, heat shock protein (HSP)70, HSP83, aldolase, enolase, triosephosphate isomerase, protein disulfideisomerase and calreticulin. This study substantiates the usefulness of proteomics in characterizing a complex protein fraction (F2) map of soluble L. donovani promastigote antigen identified as Th1 stimulatory for its potential as vaccine targets against VL.

Journal ArticleDOI
TL;DR: Leishmania donovani was identified as the agent of Sri Lanka cutaneous leishmaniasis and it was shown that these parasites are closely related to those causing visceral leish maniasis in the Indian subcontinent.
Abstract: To investigate the relationship of cutaneous leishmaniasis isolates from Sri Lanka to known species, we performed DNA sequencing and microsatellite analyses. We identified Leishmania donovani as the agent of Sri Lanka cutaneous leishmaniasis and showed that these parasites are closely related to those causing visceral leishmaniasis in the Indian subcontinent.

Journal ArticleDOI
29 Aug 2007-Vaccine
TL;DR: It is suggested that an immune modulation towards Th1 is effective for both successful vaccination and immunotherapy.

Journal ArticleDOI
TL;DR: The results highlight the need to adjust the currently used Leishmania drug susceptibility assays if they are to be used for prognosis of in vivo SSG treatment outcome, and characterize the in vitro antimony susceptibility of clinical isolates of Nepalese VL patients.

Journal ArticleDOI
TL;DR: Miltefosine is the first orally administered drug which has shown efficacy in the treatment of VL; it has not been adequately evaluated in thereatment of DCL.
Abstract: Summary Background Diffuse cutaneous leishmaniasis (DCL), although rare, is profoundly incapacitating. At present there is no successful treatment for this progressive protozoan infection, which is associated with the absence of specific cell-mediated immunity (CMI) to Leishmania. This disease shares features with visceral leishmaniasis (VL), including specific CMI inactivity during active disease and a heavy parasitic burden, but VL responds well to treatment. Miltefosine is the first orally administered drug which has shown efficacy in the treatment of VL; it has not been adequately evaluated in the treatment of DCL. Objectives To evaluate the efficacy of miltefosine in the treatment of DCL, using clinical, parasitological, histopathological and immunological criteria. Methods Sixteen patients with DCL were treated with miltefosine, 2·0–2·5 mg kg−1 daily, for variable periods of time (75–218 days). Patients were hospitalized for the first month and evaluated every 2 weeks until the termination of treatment with routine laboratory chemistry, percentage clinical improvement, presence of parasites in skin smears, growth of parasites in culture medium and in hamsters, histopathological characteristics of the granulomas, adverse side-effects, and reactivity to leishmanin skin test antigen. Further cycles of treatment were given in some of these patients, particularly after suspension of treatment was followed by relapse. Results Patients showed dramatic clinical improvement and reduction in the parasite burden by day 15 after the initiation of treatment, which continued while treatment was maintained. By day 45, 15 patients showed 80–90% clinical improvement. Nevertheless, suspension of treatment was followed by the development of new lesions in all but one patient. Inoculation in hamsters was observed to be the most sensitive technique to detect persisting parasites. Adverse events were very mild. Conclusions Miltefosine produced a dramatic clinical and parasitological response in patients with DCL and improvement continued during drug administration, but with a single exception all patients presented new lesions after suspension of treatment. There was no histological or skin test evidence to suggest the development of CMI during treatment, which may be an indispensable criterion for the evaluation of potentially effective drugs against DCL.

Journal ArticleDOI
TL;DR: The need to explore cyclodextrin-based compounds, which modulate host membrane cholesterol levels, as a possible therapeutic strategy against leishmaniasis in addition to other intracellular parasites is described.