Scientific Publications-2010-VL

2010

Leishmaniasis vaccines: past, present and future by F. Moddaber. International Journal of antimicrobial agents, 2010 Nov;36 Suppl 1:S58-61.
No vaccine exists against any form of leishmaniasis. Because recovery from infection is usually accompanied by a strong immunity and because it is possible to protect experimental animals against live challenge, hope for the development of a vaccine for humans has been high. However, leishmaniasis is a disease of the poor and the market for a vaccine is very limited. Until a few years ago, with minimal resources, only a pragmatic approach was possible for testing the first-generation vaccines (i.e. killed whole parasites). Recently, funding has become available for developing defined second-generation vaccines, including recombinant proteins and DNA constructs. With new adjuvants also being developed there is new hope, and several new vaccines are in development against leishmaniasis.
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Paromomycin for the Treatment of Visceral Leishmaniasis in Sudan: A Randomized, Open-Label, Dose-Finding Study by Musa A, Younis B, Fadlalla A, Royce C, Balasegaram M, wasunna M, Hailu A, Edwards T, Omollo R, Mudawi M, Kokwaro G, El-Hassan A, Khalil E. PLoS NTD, 2010 October, 4(10):e855
A recent study has shown that treatment of visceral leishmaniasis (VL) with the standard dose of 15 mg/kg/day of paromomycin sulphate (PM) for 21 days was not efficacious in patients in Sudan. We therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days.
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Geographical Variation in the Response of Visceral Leishmaniasis to Paromomycin in East Africa: A Multicentre, Open-Label, Randomized Trial by Hailu A, Musa A, Wasunna M, Balasegaram M, Yifru S, Mengistu G, Hurissa Z, Hailu W, Weldegebreal T, Tesfaye S, Makonnen E, Khalil E, Ahmed O, Fadlalla A, El-Hassan A, Raheem M, Muellerm, Koummuki Y, Rashid J, Mbui J, Mucee G, Njoroge S, Manduku V, Musibi A, Mutuma G, Kirui F, Lodenyo H, Mutea D, Kirigi G, Edwards T, Smith P, Muthami L, Royce C, Ellis S, Alobo M, Omollo R, Kesusu J, Owiti R, Kinuthia J, for the Leishmaniasis East Africa Platform (LEAP) group. PLoS NTD, 2010 October, 4(10):e709
Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India.
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Cost-Effectiveness Analysis of Combination Therapies for Visceral Leishmaniasis in the Indian Subcontinent by Meheus F, Balasegaram M, Olliaro P, Sundar S, Rijal S, Faiz Md. Al, Boelaert M. PLoS NTD, 2010 September, 4(9):e818
Visceral leishmaniasis is a systemic parasitic disease that is fatal unless treated. The article assesses the cost and costeffectiveness of alternative strategies for the treatment of visceral leishmaniasis in the Indian subcontinent. In particular it examines whether combination therapies are a cost-effective alternative compared to monotherapies.
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Antileishmanial High-Throughput Drug Screening Reveals Drug Candidates with New Scaffolds by Siqueira-Neto J L, Song O-R., Oh H, Sohn J-H, Yang G, Nam J, Jang J, Cechetto J, Lee C B, Moon S, Genovesio A, Chatelain E, Christophe T, Freitas-Junior L H. PLoS Neglected Tropical Diseases, 2010 May, Volume 4, Issue 5.
Drugs currently available for leishmaniasis treatment often show parasite resistance, highly toxic side effects and prohibitive costs commonly incompatible with patients from the tropical endemic countries. In this sense, there is an urgent need for new drugs as a treatment solution for this neglected disease. Here we show the development and implementation of an automated high-throughput viability screening assay for the discovery of new drugs against Leishmania. Assay validation was done with Leishmania promastigote forms, including the screening of 4,000 compounds with known pharmacological properties. In an attempt to find new compounds with leishmanicidal properties, 26,500 structurally diverse chemical compounds were screened. A cut-off of 70% growth inhibition in the primary screening led to the identification of 567 active compounds. Cellular toxicity and selectivity were responsible for the exclusion of 78% of the pre-selected compounds. The activity of the remaining 124 compounds was confirmed against the intramacrophagic amastigote form of the parasite. In vitro microsomal stability and cytochrome P450 (CYP) inhibition of the two most active compounds from this screening effort were assessed to obtain preliminary information on their metabolism in the host. The HTS approach employed here resulted in the discovery of two new antileishmanial compounds, bringing promising candidates to the leishmaniasis drug discovery pipeline.
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Combination therapy for visceral leishmaniasis by van Griensven J, Balasegaram M, Meheus F, Alvar J, Lynen L, Boelaert M. In Lancet Infect Dis 2010; 10: 184–94
Combination therapy for the treatment of visceral leishmaniasis has increasingly been advocated as a way to increase treatment efficacy and tolerance, reduce treatment duration and cost, and limit the emergence of drug resistance. The authors reviewed the evidence and potential for combination therapy, and the criteria for the choice of drugs in such regimens.
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