Shyam Sundar

..We speculate that protein phosphorylation may play a role in signal transduction pathway in the parasite after exposure to drug-conferring resistance...

..We wanted to determine whether the efficacy of a single infusion of liposomal amphotericin B was inferior to conventional parenteral therapy, consisting of 15 alternate-day infusions of amphotericin B deoxycholate...

..Our objective was to evaluate oral miltefosine for its potential to provide effective as well as tolerable treatment for this disease...

..Shorter and more acceptable regimens are needed for the treatment of post-kala-azar dermal leishmaniasis. Treatment of CL remains one of the neglected areas of leishmaniasis as data are scarce and drawn from uncontrolled studies...

..Its unrestricted use has raised concern about its continued effectiveness. This study evaluates the efficacy and safety of miltefosine for the treatment of VL after a decade of use in India...

..Early diagnosis, complete treatment of cases, integrated vector management, effective disease surveillance, and clinical and operational research should be the five key components of the strategy to achieve this goal...

..These new strategies are likely to minimize drug degradation and loss, increase drug availability, and opens up new vistas for drug delivery...

..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...

..This method is simple and well tolerated and has good potential for development, showing 83% sensitivity with 90.56% specificity in control groups...

..Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically...

..Improved treatment approaches are needed for visceral leishmaniasis. We assessed the efficacy and safety of three potential short-course combination treatments compared with the standard monotherapy in India...

..To determine the cost of kala-azar (KA) to patients in Bihar, India...

..daily administration) and dose (1 vs. 0.75 mg/kg) and to determine whether the duration of amphotericin B treatment in Bihar, India, can be shortened to 15 days...

..Treatment of visceral leishmaniasis (VL) is far from satisfactory. There is an urgent need for a therapy that is efficacious, safe, affordable, and of short duration...

..In this study, ABLE was safe and had excellent efficacy when given as a bolus of 15 mg/kg. More studies with larger number of patients and higher doses are needed to establish acceptable, safe and efficacious regimen...

....

..986). Although DAT-FD and rK-39 strip test were highly sensitive with excellent specificity, the ease of use of the latter makes it most suitable for the diagnosis of VL in the field conditions...

..There was no dose response linear correlation. In this preliminary study, AB formulated in a lipid emulsion vehicle was safe and effective for the treatment of VL in India...

..Safe, effective, and affordable new therapies are needed. We conducted a randomized, controlled, phase 3 open-label study comparing paromomycin, an aminoglycoside, with amphotericin B, the present standard of care in Bihar, India...

..All these factors increase the cost of the treatment. The development of resistance to pentavalent antimonials in patients with visceral leishmaniasis in North Bihar, India, has added another dimension to the problem...

..8-94.4%) for sitamaquine and 95% (95% confidence interval = 75.1-99.9) for AmB. Sitamaquine can be taken regardless of food intake, was generally well tolerated, and showed potential efficacy in patients with visceral leishmaniasis...

..The aim of the present study was to compare the efficacy of a nano form of amphotericin B deoxycholate with that of conventional amphotericin B deoxycholate for the treatment of visceral leishmaniasis...

....

..Variants at CXCR1 and CXCR2 have been associated with susceptibility to cutaneous and mucocutaneous leishmaniasis in Brazil. Here we investigate the role of CXCR1/CXCR2 in visceral leishmaniasis (VL) in India...

..yielded comparable results for symptomatic infection and identified apparent subclinical infection in 15 to 32% of healthy residents in a region where visceral leishmaniasis is highly endemic...

..Thus, a diagnostic protocol was devised for rapid, sensitive and cost effective identification of the opportunistic enteric protozoa...

..Because approximately one-half of the visceral leishmaniasis patients worldwide are children, we performed a Phase I/II dose ranging study in the pediatric population in India...

..Clinical Trials.gov identification number: NCT00371995...

..These findings provide direct support for targeting IL-10 as an approach to therapy in human VL...

..Miltefosine may be particularly advantageous because it can be administered orally. It may also be helpful in regions where parasites are resistant to current agents...

..This study describes the antileishmanial efficacy of the novel drug formulation of amphotericin B (AmB) attached to functionalized carbon nanotubes (f-CNTs) and compares it with AmB...

..Recent epidemiological reports indicate that asymptomatic human infections with Leishmania donovani, the causative agent of visceral leishmaniasis or Kala-azar (KA), occur frequently in India. We explored markers of infection...

....

....

..5 mg/kg daily for 28 days) was established with a cure rate (94%) similar to that seen in adults. Miltefosine is the first oral antileishmanial drug with a high degree of safety and efficacy for the treatment of VL...

..To determine the frequency of adrenal, thyroid and gonadal dysfunction in HIV positive male patients and to evaluate the endocrine function at different level of CD4 cell counts...

..However, cost is a major constraint in the use of lipid formulations of amphotericin B. Amphotericin B colloidal dispersion (ABCD), which is a less expensive lipid formulation, has not been tested for the treatment of VL in India...

..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...

....

..Results suggest the presence of Th-1 type immunostimulatory molecules in these sub-fractions which may further be exploited for developing a successful subunit vaccine from the less explored pathogenic stage against VL...

..Further analysis showed that it is a member of the heat shock protein family of 70 kDa, designated as BHUP1, and has great potential in the diagnosis of VL...

..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...

..In this study, using the hamster model, we have shown that this novel formulation of AmB can be administered orally, resulting in 99% inhibition of parasite growth following a 5-day course at 15 mg/kg body weight...

..Also, a lack of sensitivity of the LST was observed in cured VL patients. An LST antigen produced from L. donovani strains from India should be explored...

..Overexpression and underexpression of proteins were observed in the 65- to 80-kDa range and at 20 kDa, respectively...

..However, there was no significant difference in disease conversion among children (5-15 years of age) and adults (> 15 years of age). Seropositivity among asymptomatic persons is not a predictor for development of VL...

..Oral miltefosine appears to be an important alternative for the treatment of PKDL in India and confirmatory studies in controlled clinical trials are needed...

..Sergentomyia species are the most common species of sand fly. Knowledge of the infection rate in female P. argentipes may help in predicting severity of disease and in vector elimination programs...

..Further studies may help prioritize antigens for clinical development of a subunit vaccine against VL...

..Plates could be easily monitored, and growth could be rapidly detected. Moreover, parasite number may be estimated using this technique...

....

..This study was aimed at determining the prevalence of ZDV induced anaemia in HIV infected patients initiated on ZDV containing antiretroviral therapy regimen and also to find out the correlates, if any, for causing ZDV induced anaemia...

..This study describes parasite kinetics in the blood of visceral leishmaniasis patients treated with liposomal amphotericin B (L-AmB) or a preformed fat emulsion of amphotericin B (ApL) using real-time quantitative PCR (qPCR)...

..With serum, sensitivity was 100% whereas the specificity was 100%, 92.4% and 95.55% for the respective control groups. In the present format, the immunochromatographic strips cannot be used for the diagnosis of VL using urine samples...

..In recent years, there has been a steady erosion in the efficacy of pentavalent antimony to cure visceral leishmaniasis in Bihar, India. In addition, several new antileishmanial formulations have become available...

....

..Each of the restriction enzyme produced a species specific restriction patterns, which can easily be used to identify specific sand fly species. This technique can be used in the identification of sand fly species...

..The prevalence of asymptomatic infections with Leishmania donovani and their role in transmission dynamics are not well understood. We report data from a sero-survey in Bihar...

....

..This study is the first of its kind in this area where an attempt was made to correlate seasonal variation and intestinal protozoan infestations...

..chagasi) and crude soluble antigen (CSA) for the serodiagnosis of Indian visceral leishmaniasis (VL) patients by quantitative ELISA...

..Positive and negative predictive values were 0.994 and 0.788, respectively. KAtex is a promising test, and in a simplified and improved format it could be applied meaningfully in the diagnosis of VL...

....

..The present study was planned to design a Leishmania specific diagnostic assay and to evaluate its sensitivity and specificity on a sample size, which to the best of our knowledge is the largest ever screened in one study...

..Moreover, the persistence of reactivity with the 65- and 70-kDa bands in the sera of all groups shows its promise as a diagnostic and prognostic tool...

..We propose an interferon-gamma release assay (IFN-γRA) as a novel marker for latent L. donovani infection...

..The antigen identified via a proteomics-based approach has a strong potential for further development as a diagnostic tool for VL...

..In contrast to earlier reports, our data suggest that significant genetic polymorphisms exist in L. donovani strains in Bihar, India. Our results confirm the presence of 2 zymodemes in India...

..To understand the VL seasonality, annual and monthly variations of VL incidence and its relationship to meteorological variables, the numbers of VL cases reported in Muzaffarpur district, Bihar, India from 1990 to 2008 were studied...

..A simple, rapid, non invasive, accurate and cost effective marker of active VL, which can be used in field conditions, is necessary to improve diagnosis of VL...

..There is an increasing incidence of abdominal tuberculosis with the advent of HIV infection. This study was aimed at determining the pattern of presentation of abdominal tuberculosis on ultrasonography (USG) in HIV positive patients...

..These results suggest that low NADH-oxidase, NADPH-oxidase and myeloperoxidase activities may account for persistence of Leishmania parasites in visceral leishmaniasis...

..Two isolates were also transfected with green fluorescent protein (GFP) for the development of in vitro assay for studying antileishmanial activities of new and reference drugs in macrophages by flow cytometry...

..Nephrotic syndrome (3% [3 of 120]) and glomerulonephritis (2% [2 of 120]) were also reported and require further investigation. Oral sitamaquine demonstrated efficacy in Indian VL and was well tolerated...

..In serum, specificity was 97%, 88.5%, and 89% by ELISA and 100%, 94.7%, and 95.5% by ICT in nonendemic, endemic, and different diseases, respectively. Saliva is not suitable for diagnosis of VL because of low sensitivity...

..This clinical trial shows that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without history of previous infection with Leishmania donovani...

..Unfortunately, up to 32% healthy individuals from endemic region test positive with this antigen. There is an urgent need to search for a more specific antigen with sensitivity similar to rK39...

..and L. donovani in this isolate. We consider that mixed infection may be present in the patients themselves, Leptomonas persisting in them because of the immuno-suppression associated with Kala-azar...

..Poor knowledge of the study subjects about the disease and breeding sites of the vector underscores the need for health educational campaigns if the elimination program is to succeed...

..A shift from monotherapy to multi-drug combinations of short courses delivered at no or affordable cost, through directly observed therapy, seems to be the only way to develop the treatment of this disease...

..Effusions were small, haemodynamically insignificant and resolved spontaneously. We conclude that pericardial effusion may occur in VL patients with heavy parasitaemia...

....

..Tropica causes nearly 25% of current kala-azar cases in India. It was also suggested that this might be in some way related to the unresponsiveness to pentavalent antimonials in the field...

..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...

..This trial indicates that miltefosine is as effective and well tolerated in Indian children with VL as in adults and that it can be recommended as the first choice for treatment of childhood VL in India...

..major, and the resulting cells became 10-fold more resistant to Sb(III). This is the first report of the uptake of a metalloid drug by an aquaglyceroporin in Leishmania, suggesting a strategy to reverse resistance in the field...

....

..The system is in routine use at the Central Drug Research Institute, Lucknow, India, for high-throughput screening of newly synthesized compounds...

..Our results also indicate that lovastatin, which can inhibit both P-gp and MRP1, might be beneficial for reverting Sb resistance in leishmaniasis as well as drug resistance in other clinical situations, including cancer...

..1 promoted antimonial-induced PCD but protected against miltefosine-induced PCD. This study highlights the important role of PCD in drug susceptibility/resistance in the protozoan parasite Leishmania...

..To identify and quantify the direct and indirect economic cost of treatment for visceral leishmaniasis (VL) with conventional Amphotericin B deoxycholate, currently the first-line treatment in Muzaffarpur...

..We evaluated a DAT with freeze-dried (FD) antigen and compared it with the LQ antigen version...

..Unravelling the molecular mechanisms of clinical resistance could allow the prevention and circumvention of resistance, as well as rational drug design for the treatment of drug-resistant Leishmania...

..Given the constraints of indoor residual spraying, it is worthwhile to further explore the use of ITNs, in particular long lasting ITNs, as an additional tool in the VL elimination initiative...

..These results suggest the possible role of thiols and MRPA in antimony resistance in field isolates...