The Experts below are selected from a list of 36399 Experts worldwide ranked by ideXlab platform
Shyam Sundar - One of the best experts on this subject based on the ideXlab platform.
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eliminating Visceral Leishmaniasis in south asia the road ahead
BMJ, 2019Co-Authors: Suman Rijal, Shyam Sundar, Dinesh Mondal, Jorge Alvar, Pradeep Das, Marleen BoelaertAbstract:Suman Rijal and colleagues highlight lessons from a regional collaboration to eliminate Visceral Leishmaniasis and identify priorities for the post-elimination plan
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elimination of Visceral Leishmaniasis on the indian subcontinent
Lancet Infectious Diseases, 2016Co-Authors: Om Prakash Singh, Marleen Boelaert, Epco Hasker, Shyam SundarAbstract:Summary Visceral Leishmaniasis is a serious public health problem on the Indian subcontinent, causing high morbidity and mortality. The governments in the region launched a Visceral Leishmaniasis elimination initiative in 2005. We review knowledge gaps and research priorities. Key challenges include low coverage of health services for those most at risk, drug resistance, the absence of a vaccine, and the complex biology of the sandfly–human host transmission cycle. Vector control is an essential component, but innovation in this field is insufficient. Substantial progress has been made in the area of diagnostic, therapeutic, and vaccine development, but there are still many hurdles to overcome. For Visceral Leishmaniasis elimination to become a reality, effective deployment of these existing and new tools is essential. A strong commitment at community level is imperative, and appropriate diagnostic and treatment services as well as effective epidemiological surveillance need to be ensured.
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Visceral Leishmaniasis in the indian subcontinent modelling epidemiology and control
PLOS Neglected Tropical Diseases, 2011Co-Authors: Anette Stauch, Shyam Sundar, Marleen Boelaert, Suman Rijal, Albert Picado, R R Sarkar, Bart Ostyn, Jeanclaude Dujardin, Hanspeter DuerrAbstract:Background In the Indian subcontinent, about 200 million people are at risk of developing Visceral Leishmaniasis (VL). In 2005, the governments of India, Nepal and Bangladesh started the first regional VL elimination program with the aim to reduce the annual incidence to less than 1 per 10,000 by 2015. A mathematical model was developed to support this elimination program with basic quantifications of transmission, disease and intervention parameters. This model was used to predict the effects of different intervention strategies.
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Visceral Leishmaniasis elimination with existing interventions
Lancet Infectious Diseases, 2011Co-Authors: Greg Matlashewski, Shyam Sundar, P K Sinha, Dinesh Mondal, Axel Kroeger, Byron Arana, Sujit Battacharya, Pradeep Das, Suman Rijal, Dan ZilbersteinAbstract:The world's burden of infectious diseases can be substantially reduced by more-effective use of existing interventions. Advances in case detection, diagnosis, and treatment strategies have made it possible to consider the elimination of Visceral Leishmaniasis in the Indian subcontinent. The priority must now be to effectively implement existing interventions at the community level by actively finding cases in endemic villages and treating them with single-dose liposomal amphotericin B at primary-health-care centres. Once the elimination target of one case per 10,000 population has been reached, combination therapies involving miltefosine and paromomycin can be introduced to ensure long-term availability of several drugs for Visceral Leishmaniasis and to protect against resistance.
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diagnosis of Visceral Leishmaniasis
Transactions of The Royal Society of Tropical Medicine and Hygiene, 2011Co-Authors: Pankaj Srivastava, Anand Dayama, Sanjana Mehrotra, Shyam SundarAbstract:Leishmaniasis is a vector-borne disease with up to 350 million people at risk of infection worldwide. Among its different clinical manifestations, Visceral is the most severe form. Since clinical features of Visceral Leishmaniasis (VL) mimic several other common diseases, accurate diagnosis is crucial as the treatment is associated with significant toxicity. Invasive and risky techniques involving demonstration of the parasites in stained preparations from splenic and bone marrow aspirate is still the gold standard for VL diagnosis. Serological tests using rK39 in ELISA or rapid immunochromatographic format, Direct Agglutination Test (DAT), immunoblotting have issues related to a significant proportion of asymptomatic individuals being positive with these tests and their inability to diagnose relapses as these remain positive for several months to years after cure. PCR is the most common molecular technique successfully used for diagnosis and differentiation of species. Through this review we focus extensively on the comparative utilities of the various diagnostic tools currently available for VL, describing in depth their advantages and disadvantages, addressing the recent advances attained in the field. 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.
Jonathan Berman - One of the best experts on this subject based on the ideXlab platform.
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oral miltefosine treatment in children with mild to moderate indian Visceral Leishmaniasis
Pediatric Infectious Disease Journal, 2003Co-Authors: Shyam Sundar, T. K. Jha, Herbert Sindermann, Klaus Junge, Peter Bachmann, Jonathan BermanAbstract:BACKGROUND: Miltefosine is the first oral drug with demonstrable success in treating Visceral Leishmaniasis in adults. 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. METHODS: Thirty-nine (39) children (defined as < 12 years of age) with Visceral Leishmaniasis demonstrated by parasites in splenic aspirates, were treated with oral miltefosine daily for 28 days: 21 patients received 1.5 mg/kg/day (Group A); and 18 patients received 2.5 mg/kg/day (Group B). About one-half of these children had failed prior antileishmanial treatment. RESULTS: All patients were parasitologically negative and symptomatically improved by the end of therapy on Day 28 of therapy; the initial parasitologic cure rate was 100%. Two patients in each treatment group relapsed with fever, splenomegaly and parasite-positive splenic aspirates by the end of the 6-month follow-up. The per protocol final clinical cure rate was 19 of 21 = 90% in Group A and 15 of 17 = 88% in Group B. Miltefosine was well-tolerated. As per the adult experience, gastrointestinal adverse events were seen: 33 and 39% of children experienced vomiting and 5 and 17% experienced diarrhea in Groups A and B, respectively, but all episodes were mild to moderate in severity and commonly lasted <1 day without symptomatic treatment. CONCLUSION: Oral miltefosine was safe and approximately 90% effective in this initial clinical trial of childhood Visceral Leishmaniasis.
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Oral Miltefosine for Indian Visceral Leishmaniasis
New England Journal of Medicine, 2002Co-Authors: Shyam Sundar, T. K. Jha, Anthony Bryceson, Juergen Engel, Herbert Sindermann, Christina Fischer, Klaus Junge, Jonathan BermanAbstract:Background There are 500,000 cases per year of Visceral Leishmaniasis, which occurs primarily in the Indian subcontinent. Almost all untreated patients die, and all the effective agents have been parenteral. Miltefosine is an oral agent that has been shown in small numbers of patients to have a favorable therapeutic index for Indian Visceral Leishmaniasis. We performed a clinical trial in India comparing miltefosine with the most effective standard treatment, amphotericin B. Methods The study was a randomized, open-label comparison, in which 299 patients 12 years of age or older received orally administered miltefosine (50 or 100 mg [approximately 2.5 mg per kilogram of body weight] daily for 28 days) and 99 patients received intravenously administered amphotericin B (1 mg per kilogram every other day for a total of 15 injections). Results The groups were well matched in terms of age, weight, proportion with previous failure of treatment for Leishmaniasis, parasitologic grade of splenic aspirate, and sple...
Susan Wyllie - One of the best experts on this subject based on the ideXlab platform.
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cyclin dependent kinase 12 is a drug target for Visceral Leishmaniasis
Nature, 2018Co-Authors: Susan Wyllie, Stephen Patterson, Michael G Thomas, Sabrinia Crouch, Manu De Rycker, Rhiannon Lowe, Stephanie Gresham, Michael D Urbaniak, Thomas D OttoAbstract:Visceral Leishmaniasis causes considerable mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. Here we describe the development of an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of Visceral Leishmaniasis, has suitable physicochemical, pharmacokinetic and toxicological properties for further development, and has been declared a preclinical candidate. Detailed mode-of-action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a druggable target for Visceral Leishmaniasis.
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the anti tubercular drug delamanid as a potential oral treatment for Visceral Leishmaniasis
eLife, 2016Co-Authors: Stephen Patterson, Susan Wyllie, Laste Stojanovski, Frederick R C Simeons, Suzanne Norval, Kevin D Read, Jennifer L Auer, Maria Osunacabello, Alan H FairlambAbstract:Better, safer, oral drugs are desperately needed for the treatment of Visceral Leishmaniasis, a parasitic infectious disease that causes an estimated 40,000 deaths a year, predominantly in South America, East Africa and the Indian subcontinent. The parasite that causes Visceral Leishmaniasis is transmitted between individuals by blood-sucking sandflies, and there are currently no vaccines that protect against the disease. In addition, all currently available drug treatments have serious limitations – they are expensive, toxic, have to be applied over a long period of time (mainly by injection) and may become ineffective as the parasites adapt to resist the drug. A cost-effective way to find a new treatment for a disease is to repurpose existing clinically approved drugs that are used to treat other diseases. Patterson, Wyllie et al. now report that a drug called delamanid, which was recently approved for the treatment of tuberculosis, can cure Visceral Leishmaniasis in mice. The drug worked when applied orally at doses that might be achievable in human patients, and can also kill parasites obtained from human patients. Patterson, Wyllie et al. also provide evidence that suggests that delamanid is processed in the parasites by an unknown enzyme. However, this enzyme is not the one that activates a different class of drugs that are used to treat Visceral Leishmaniasis. Future studies now need to identify the enzyme that is targeted by delamanid, and could investigate combinations of drugs that slow the emergence of resistant parasites and improve delamanid’s safety and effectiveness. Clinical trials are required to test how well delamanid treats Visceral Leishmaniasis in humans.
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the anti trypanosome drug fexinidazole shows potential for treating Visceral Leishmaniasis
Science Translational Medicine, 2012Co-Authors: Susan Wyllie, Stephen Patterson, Laste Stojanovski, Frederick R C Simeons, Suzanne Norval, Robert Kime, Kevin D Read, Alan H FairlambAbstract:Safer and more effective oral drugs are required to treat Visceral Leishmaniasis, a parasitic disease that kills 50,000 to 60,000 people each year in parts of Asia, Africa, and Latin America. Here, we report that fexinidazole, a drug currently in phase 1 clinical trials for treating African trypanosomiasis, shows promise for treating Visceral Leishmaniasis. This 2-substituted 5-nitroimidazole drug is rapidly oxidized in vivo in mice, dogs, and humans to sulfoxide and sulfone metabolites. Both metabolites of fexinidazole were active against Leishmania donovani amastigotes grown in macrophages, whereas the parent compound was inactive. Pharmacokinetic studies with fexinidazole (200 mg/kg) showed that fexinidazole sulfone achieves blood concentrations in mice above the EC 99 (effective concentration inhibiting growth by 99%) value for at least 24 hours after a single oral dose. A once-daily regimen for 5 days at this dose resulted in a 98.4% suppression of infection in a mouse model of Visceral Leishmaniasis, equivalent to that seen with the drugs miltefosine and Pentostam, which are currently used clinically to treat this tropical disease. In African trypanosomes, the mode of action of nitro drugs involves reductive activation via a NADH (reduced form of nicotinamide adenine dinucleotide)–dependent bacterial-like nitroreductase. Overexpression of the leishmanial homolog of this nitroreductase in L. donovani increased sensitivity to fexinidazole by 19-fold, indicating that a similar mechanism is involved in both parasites. These findings illustrate the potential of fexinidazole as an oral drug therapy for treating Visceral Leishmaniasis.
Henry W. Murray - One of the best experts on this subject based on the ideXlab platform.
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rapid noninvasive diagnosis of Visceral Leishmaniasis in india comparison of two immunochromatographic strip tests for detection of anti k39 antibody
Journal of Clinical Microbiology, 2006Co-Authors: Shyam Sundar, Radheshyam Maurya, Rakesh K Singh, K Bharti, Jaya Chakravarty, Ashish Parekh, Kailash Kumar, Henry W. MurrayAbstract:Used with blood or serum, a new anti-K39 antibody immunochromatographic strip test (IT-Leish; DiaMed AG) proved sensitive (range, 99 to 100%) and specific (range, 95 to 100%) for the noninvasive serodiagnosis of Visceral Leishmaniasis in India. Used with serum, the IT-Leish test and the existing Kalazar Detect test (InBios International, Inc.) 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.
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short course of oral miltefosine for treatment of Visceral Leishmaniasis
Clinical Infectious Diseases, 2000Co-Authors: Shyam Sundar, Andreas Voss, Christina Fischer, Peter Bachmann, Anand Makharia, Deepak K More, Gaurav Agrawal, Henry W. MurrayAbstract:A total of 54 Indian patients with Visceral Leishmaniasis were treated with oral miltefosine, 50 mg given twice daily, for 14 days (18 patients; group A), 21 days (18; group B), or 28 days (18; group C). Cure was achieved in 89% of group A, 100% of group B, and 100% of group C. Adverse reactions were self-limited and primarily mild. The 21-day miltefosine regimen combines high-level efficacy, convenient dosing, and a relatively short duration.
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Trial of oral miltefosine for Visceral Leishmaniasis
The Lancet, 1998Co-Authors: Shyam Sundar, Frank Rosenkaimer, Manoj K. Makharia, Ashish K Goyal, Ashim K Mandal, Andreas Voss, Peter Hilgard, Henry W. MurrayAbstract:Summary Background There is no effective oral treatment for Visceral Leishmaniasis (kala-azar), a disseminated intracellular protozoal infection that occurs worldwide. Miltefosine, an alkyl phospholipid developed as an oral antineoplastic agent, is active against Visceral infection in animal models. We tested safety, tolerance, and efficacy of miltefosine in kalaazar. Methods Oral doses of miltefosine were given to six groups of five Indian men for 28 days: 50 mg every second day (group 1), 100 mg every second day (group 2), 100 mg/day (group 3), 150 mg/day (group 4), 200 mg/day (group 5), and 250 mg/day (group 6). Assessment for apparent cure—taken as an afebrile state with decreased spleen size and a splenic-aspirate parasite-density score of 0-was done on days 14 and 28. Definitive cure at 8 months required a parasite-free bone-marrow aspirate and no clinical evidence of relapse. Findings 21 of 30 patients were apparently cured on day 14. Transient episodes of vomiting and diarrhoea, were common during weeks 1–2 and were seen in 22 patients. Four other patients in groups 5 and 6 had miltefosine withdrawn after 7–10 days because of vomiting. One patient in group 6 developed renal insufficiency and severe diarrhoea and died on day 21. On day 28, all 29 remaining patients were apparently cured. By 8 months, seven of ten patients in groups 1 and 2 had relapsed; however, 18 of 19 patients treated daily (groups 3–6) appeared to be cured. Among the 21 definitive cures were the four patients treated for 10 days or less and 12 for whom previous therapy with pentavalent antimony had failed. Interpretation Treatment with miltefosine at 100–150 mg/day for 4 weeks has promise as an effective oral treatment of Visceral Leishmaniasis including antimonyresistant infection.
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short course low dose amphotericin b lipid complex therapy for Visceral Leishmaniasis unresponsive to antimony
Annals of Internal Medicine, 1997Co-Authors: Shyam Sundar, N Agrawal, Prabhat R Sinha, Gary S Horwith, Henry W. MurrayAbstract:Background: Visceral Leishmaniasis (kala-azar) is a world-wide, disseminated intracellular protozoal infection for which prolonged, conventional therapy with pentavalent antimony has become increas...
Marleen Boelaert - One of the best experts on this subject based on the ideXlab platform.
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eliminating Visceral Leishmaniasis in south asia the road ahead
BMJ, 2019Co-Authors: Suman Rijal, Shyam Sundar, Dinesh Mondal, Jorge Alvar, Pradeep Das, Marleen BoelaertAbstract:Suman Rijal and colleagues highlight lessons from a regional collaboration to eliminate Visceral Leishmaniasis and identify priorities for the post-elimination plan
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elimination of Visceral Leishmaniasis on the indian subcontinent
Lancet Infectious Diseases, 2016Co-Authors: Om Prakash Singh, Marleen Boelaert, Epco Hasker, Shyam SundarAbstract:Summary Visceral Leishmaniasis is a serious public health problem on the Indian subcontinent, causing high morbidity and mortality. The governments in the region launched a Visceral Leishmaniasis elimination initiative in 2005. We review knowledge gaps and research priorities. Key challenges include low coverage of health services for those most at risk, drug resistance, the absence of a vaccine, and the complex biology of the sandfly–human host transmission cycle. Vector control is an essential component, but innovation in this field is insufficient. Substantial progress has been made in the area of diagnostic, therapeutic, and vaccine development, but there are still many hurdles to overcome. For Visceral Leishmaniasis elimination to become a reality, effective deployment of these existing and new tools is essential. A strong commitment at community level is imperative, and appropriate diagnostic and treatment services as well as effective epidemiological surveillance need to be ensured.
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Visceral Leishmaniasis in the indian subcontinent modelling epidemiology and control
PLOS Neglected Tropical Diseases, 2011Co-Authors: Anette Stauch, Shyam Sundar, Marleen Boelaert, Suman Rijal, Albert Picado, R R Sarkar, Bart Ostyn, Jeanclaude Dujardin, Hanspeter DuerrAbstract:Background In the Indian subcontinent, about 200 million people are at risk of developing Visceral Leishmaniasis (VL). In 2005, the governments of India, Nepal and Bangladesh started the first regional VL elimination program with the aim to reduce the annual incidence to less than 1 per 10,000 by 2015. A mathematical model was developed to support this elimination program with basic quantifications of transmission, disease and intervention parameters. This model was used to predict the effects of different intervention strategies.
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insecticide susceptibility of phlebotomus argentipes in Visceral Leishmaniasis endemic districts in india and nepal
PLOS Neglected Tropical Diseases, 2010Co-Authors: Diwakar Singh Dinesh, Marleen Boelaert, Pradeep Das, Suman Rijal, Murari Lal Das, Albert Picado, Lalita Roy, Shri Singh, Marc CoosemansAbstract: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.
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cost effectiveness analysis of combination therapies for Visceral Leishmaniasis in the indian subcontinent
PLOS Neglected Tropical Diseases, 2010Co-Authors: Filip Meheus, Shyam Sundar, Piero Olliaro, Manica Balasegaram, Suman Rijal, Md Abul Faiz, Marleen BoelaertAbstract:Background Visceral Leishmaniasis is a systemic parasitic disease that is fatal unless treated. We assessed the cost and cost-effectiveness of alternative strategies for the treatment of Visceral Leishmaniasis in the Indian subcontinent. In particular we examined whether combination therapies are a cost-effective alternative compared to monotherapies. Methods and Findings We assessed the cost-effectiveness of all possible mono- and combination therapies for the treatment of Visceral Leishmaniasis in the Indian subcontinent (India, Nepal and Bangladesh) from a societal perspective using a decision analytical model based on a decision tree. Primary data collected in each country was combined with data from the literature and an expert poll (Delphi method). The cost per patient treated and average and incremental cost-effectiveness ratios expressed as cost per death averted were calculated. Extensive sensitivity analysis was done to evaluate the robustness of our estimations and conclusions. With a cost of US$92 per death averted, the combination miltefosine-paromomycin was the most cost-effective treatment strategy. The next best alternative was a combination of liposomal amphotericin B with paromomycin with an incremental cost-effectiveness of $652 per death averted. All other strategies were dominated with the exception of a single dose of 10mg per kg of liposomal amphotericin B. While strategies based on liposomal amphotericin B (AmBisome) were found to be the most effective, its current drug cost of US$20 per vial resulted in a higher average cost-effectiveness. Sensitivity analysis showed the conclusion to be robust to variations in the input parameters over their plausible range. Conclusions Combination treatments are a cost-effective alternative to current monotherapy for VL. Given their expected impact on the emergence of drug resistance, a switch to combination therapy should be considered once final results from clinical trials are available.
