S Sundar

..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...

..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...

..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...

..The public health community should work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs...

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

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..In addition to the monotherapy, efforts in development of combination chemotherapy are needed if the menace of drug resistance is to be contained...

..Lipid associated amphotericin B has an excellent safety and efficacy profile, but remains out of reach for most patients because of its high cost...

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..There was no significant difference in the cure rates of the 3 groups. Low-dose liposomal amphotericin B given for 5 days can cure most patients with Indian kala-azar...

..In a region in India where visceral infection is prevalent, strip test detection of anti-K39 IgG is a clinically promising diagnostic guide in persons with suspected kala-azar...

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..Very few adverse events (fever with rigor, in 9.8% of patients) were seen. Single-dose L-AmB (7.5 mg/kg) treatment is safe and effective, and it may be used for the mass treatment of VL in India...

..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...

..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...

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..Together, the present results provide further support for the use of ABLC in the management of VL patients who fail antimony therapy...

..To test short course, low dose liposomal amphotericin B as single or daily infusion treatment in Indian visceral leishmaniasis (kala-azar)...

..Adverse reactions were self-limited and primarily mild. The 21-day miltefosine regimen combines high-level efficacy, convenient dosing, and a relatively short duration...

..tropica. Thus, the rising incidence of clinical resistance to treatment is unlikely to be due to a different species causing kala-azar in north Bihar...

..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...

..The extremely high levels of anti-rK39 antibodies in VL cases suggest the application of rK39 for sensitive and specific serodiagnosis, and rK39 ELISA is also valuable in monitoring drug therapy and detecting relapse of the disease...

..Sb induced long-term cure in 35% (95% confidence interval [CI], 28%-42%) of those in Bihar versus 86% (95% CI, 79%-93%) of those in Uttar Pradesh. In Bihar, the center of the Indian epidemic, traditional Sb treatment should be abandoned...

..Since the disease vector continues to be present in the study area, the health authorities should take strong steps to control the disease...

..Similarly, the rK39 strip test is as sensitive as the DAT, but the strip test's greater convenience of use makes it a better tool for diagnosis of VL in peripheral areas of endemic regions...

..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...

..The simple technique of measuring of osmolarity may help identify inappropriately manufactured drug...

..In the current study we assessed knowledge, attitude and practice of these village health workers in relation to VL. Main objective was to assess the feasibility of their involvement in VL control...

..We analysed the operational feasibility and cost of such periodic random surveys as compared with health facility-based routine monitoring...

..3%) and diarrhea (12.7%). CD4 counts of the patients were significantly inversely correlated with the number of symptoms and the number of opportunistic infections (correlation coefficient were -.289 and -.236 respectively)...

..More commonly PRCA is associated with thymoma or viral infections. Steroids and other immunosuppressive drugs are the preferred treatment of PRCA...

..In the majority of patients, it can identify a successful disease outcome; however, its translation into the field setting remains a major challenge...

..To evaluate five kala-azar serological tests for field use...

..These results indicate that 100 mg miltefosine/day for 28 days is a promising oral-treatment regimen for VL cases, including those with antimony-unresponsive infections...

..We conclude that active VL is not associated with increased frequencies of peripheral Foxp3 Treg or accumulation at the site of infection...

..85-0.96) and 96.59% (95% CI 0.90-0.98), respectively. Our results show that rK39 and rK28 antigens have similar sensitivity and specificity and rK28 can also be used as a serodiagnostic tool in the endemic population of Bihar...

..The most common opportunistic infection was tuberculosis. CD4% correlated significantly with the deterioration of the WHO clinical stages (P<0.01) and increasing grades of protein energy malnutrition (P< 0.05)...

..There was a fair degree of correlation between platelet adhesiveness and platelet factor III availability in these patients: 50% of patients with poor platelet adhesiveness showed reduced platelet factor III availability...

..Majority of the patients survive less than 4 months. We are presenting a short series of four such cases, who had a good clinical response to combination chemotherapy...

..As the constraints for official reporting at the block and the district levels are similar, the underreporting at district level was also assumed to be similar. This finding has significance in the preparation for elimination programme...

..To protect the already scarce inventory of antileishmanial drugs, it is time that combination chemotherapy is introduced for the treatment of VL in India...

..Furthermore, the monocytes regained respiratory burst activity as the antileishmanial therapy progressed, suggesting that an immune-based mechanism is involved in successful drug therapy...

..It may be used for the prognosis of the disease as antigen becomes undetectable in urine after 30 days of the completion of the treatment. Alternatively, it can be used as an adjunct with rK39 for sero-epidemiological surveys...

..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...

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..To assess HIV associated tuberculosis in a high tuberculosis prevalence setting and its status in the clinical case definition of AIDS...

..001). In conclusion, depletion of zinc, observed in RHD, probably causes immune alterations and suggest role of zinc in immunopathogenesis of RHD. Zinc supplementation may alter the course of rheumatic fever and RHD...

..In conclusion, captopril closely followed by propranolol was the most acceptable drug with fewer adverse effects and improved sexual as well as other aspects of quality of life compared to nifedipine and atenolol...

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..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...

..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...

..Hospital-based studies have shown that oral miltefosine is a highly effective treatment for VL both in adults and in children...

..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...

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

..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...

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

..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...

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

..New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients...

..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...

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..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...

..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...

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..Interestingly, optimum Th1-responses were obtained with P4-7 suggesting the presence of immunostimulatory molecules in it and may be exploited for developing a successful subunit vaccine against VL...

..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...

..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...

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..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...

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..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...

..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...

..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...

..CONCLUSIONS: Anti-O-AcSGs were identified as an important source of CP activation under normal physiological conditions, suggesting that they play a role in conferring host protection against parasite infection...

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

..India, Bangladesh, and Nepal agreed recently to undertake measures towards the elimination of visceral leishmaniasis. The lessons learnt in Bihar could help inform policy decisions both regionally and elsewhere...

..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...

..Ten antigens were identified, five of which have not been described as leishmania antigens before. The antigens specifically react with sera of leishmania-infected patients but not of toxoplasma- or plasmodium-infected patients...

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

..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...

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..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...

..This article reviews the current situation and perspectives for diagnosis, treatment, and control of visceral leishmaniasis, and lists some priorities for research and development...

..Taken together, we conclude that this antigen-based assay is a specific and reproducible method for monitoring the disease status of VL patients and could be used in retrospective and prospective trials...

..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...

..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...

..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...

..We recommend carefully supervised spraying with DDT, surveillance to pinpoint other affected villages, and efforts to increase availability of diagnostic and treatment facilities...

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