Scientific Publications-Archives-VL

2005

Chemotherapy of trypanosomiases and leishmaniasis by Croft SL, Barrett MP, Urbina JA. Trends Parasitol. 2005 Nov;21(11):508-12.
New formulations, therapeutic switching of the established drugs amphotericin B and paromomycin, and the serendipitous discovery of miltefosine have markedly improved leishmaniasis chemotherapy in the past 21 years. The situation for the two trypanosomiases has been less encouraging. However, the appearance of not-for-profit product-development partnerships offers a new paradigm for bringing new drugs to patients.
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Advances in leishmaniasis by Murray HW, Berman JD, Davies CR, Saravia NG. Lancet. 2005 Oct 29-Nov 4;366(9496):1561-1577.
Diagnosis relies on visualising parasites in tissue or serology; culture and detection of parasite DNA are useful in the laboratory. Despite tangible advances in diagnosis, treatment, and basic scientific research, leishmaniasis is embedded in poverty and neglected. Current obstacles to realistic prevention and proper management include inadequate vector (sandfly) control, no vaccine, and insufficient access to or impetus for developing affordable new drugs.
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Control of mucocutaneous leishmaniasis, a neglected disease: results of a control programme in Satipo Province, Peru by Guthmann JP, Arlt D, Garcia LM, Rosales M, de Jesus Sanchez J, Alvarez E, Lonlas S, Conte M, Bertoletti G, Fournier C, Huari R, Torreele E, Llanos-Cuentas A. Trop Med Int Health. 2005 Sep;10(9):856-62.
Mucocutaneous leishmaniasis (MCL) is an important health problem in many rural areas of Latin America, but there are few data on the results of programmatic approaches to control the disease. We report the results of a control programme in San Martin de Pangoa District, which reports one of the highest prevalences of MCL in Peru.
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The sensitivity of clinical isolates of Leishmania from Peru and Nepal to miltefosine by Yardley V, Croft SL, De Doncker S, Dujardin JC, Koirala S, Rijal S, Miranda C, Llanos-Cuentas A, Chappuis F. Am J Trop Med Hyg. 2005 Aug;73(2):272-5.
Clinical isolates of Leishmania, from visceral leishmaniasis (VL) cases in Nepal and from cutaneous leishmaniasis (CL) cases in Peru, were cultured using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) to type species and strain. The study demonstrates a notable difference in the intrinsic sensitivity of Leishmania species to miltefosine in vitro.
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Preparation of transition-state analogues of sterol 24-methyl transferase as potential anti-parasitics by Lorente SO, Jimenez CJ, Gros L, Yardley V, de Luca-Fradley K, Croft SL, A Urbina J, Ruiz-Perez LM, Pacanowska DG, Gilbert IH. Bioorg. Med. Chem. 2005 Jul, 13: 5435-5453.
In this paper we discuss the design, synthesis and evaluation of potential transition state analogues of the enzyme D24(25)-methyltransferase (24-SMT). This enzyme is essential for the biosynthesis of ergosterol, but not required for the biosynthesis of cholesterol. A series of compounds were successfully synthesised in which mimics of the S-adenosyl methionine co-factor were attached to the sterol nucleus.
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Visceral Leishmaniasis: New Health Tools Are Needed by Hailu A, Musa A.M, Royce C, Wasunna M. PLoS Med. 2005 Jul; 2(7):e211.
Visceral leishmaniasis (VL), commonly known as kala azar, from the Hindu vernacular, is a human systemic disease caused by parasitic protozoan species of the genus Leishmania. Transmitted by the bite of the tiny and seemingly innocuous female phlebotomine sandfly, the parasite enters macrophages, where it multiplies and establishes the infection.
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2004

Novel Azasterols as Potential Agents for Treatment of Leishmaniasis and Trypanosomiasis by Lorente SO, Rodrigues JC, Jimenez Jimenez C, Joyce-Menekse M, Rodrigues C, Croft SL, Yardley V, de Luca-Fradley K, Ruiz-Perez LM, Urbina J, de Souza W, Gonzalez Pacanowska D, Gilbert IH. Antimicrob Agents Chemother. 2004 Aug;48(8):2937-50.
This paper describes the design and evaluation of novel azasterols as potential compounds for the treatment of leishmaniasis and other diseases caused by trypanosomatid parasites. The compounds prepared showed activity at micromolar and nanomolar concentrations when tested against Leishmania spp. and Trypanosoma spp. The compounds were also found to be active against the bloodstream form (trypomastigotes) of Trypanosoma brucei rhodesiense, a causative agent of African trypanosomiasis.
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Synthesis and antileishmanial activity of novel buparvaquone oxime derivatives by Mantyla A, Rautio J, Nevalainen T, Vepsalainen J, Juvonen R, Kendrick H, Garnier T, Croft SL, Jarvinen T. Bioorg Med Chem. 2004 Jul 1;12(13):3497-502.
Novel oxime derivatives (2, 3 and 5) of buparvaquone (1) and O-methyl-buparvaquone (4) were synthesized and their in vitro activities against Leishmania donovani, the causative agent of visceral leishmaniasis (VL), were determined. Buparvaquoneoxime (2) was also studied as a bioreversible prodrug structure of buparvaquone (1).
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2003

Leishmaniasis-current chemotherapy and recent advances in the search for novel drugs by Croft SL, Coombs GH. Trends Parasitol. 2003 Nov;19(11):502-8
The chemotherapy currently available for leishmaniasis is far from satisfactory. Resistance to the pentavalent antimonials, which have been the recommended drugs for the treatment of both visceral (VL) and cutaneous leishmaniasis (CL) for >50 years, is now widespread in India. Although new drugs have become available in recent years for the treatment of VL, treatment problems remain. The search for new drugs continues. Many potential drug targets have been identified in biochemical and molecular studies, and some have been validated. Attempts to exploit these targets are in progress.
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2002

Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda by Guérin P. et al, August 2002, Lancet Infect Dis 2002; 2 : 494–501.
Visceral leishmaniasis is common in less developed countries, with an estimated 500 000 new cases each year. Because of the diversity of epidemiological situations, no single diagnosis, treatment, or control will be suitable for all. This article reviews the current situation and perspectives for diagnosis, treatment, and control of visceral leishmaniasis, and lists some priorities for research and development.
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