Scientific Publications-2006-VL

2006

Miltefosine: issues to be addressed in the future by Berman J, Bryceson AD, Croft S, Engel J, Gutteridge W, Karbwang J, Sindermann H, Soto J, Sundar S, Urbina JA. Trans. R. Soc. Trop. Med. Hyg. 2006 Dec;100 Suppl 1:S41-4. Epub 2006 Jun 5.
Future issues that need to be addressed for miltefosine are efficacy against non-Indian visceral leishmaniasis, efficacy in HIV-coinfected patients, efficacy against the many forms of cutaneous and mucosal disease, effectiveness under clinical practice conditions, generation of drug resistance and the need to provide a second antileishmanial agent to protect against this disastrous event, and the ability to maintain reproductive contraceptive practices under routine clinical conditions.
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Miltefosine — discovery of the antileishmanial activity of phospholipid derivatives by Croft SL, Engel J. Trans R Soc Trop Med Hyg. 2006 Dec;100 Suppl 1:S4-8. Epub 2006 Aug 14. Review.
Miltefosine (hexadecylphosphocholine, ImpavidoTM), a novel antiprotozoal drug used for the treatment of visceral and cutaneous leishmaniasis, was identified and evaluated independently in the early 1980s as a potential anticancer drug in Germany and as an antileishmanial drug in the UK. Miltefosine is active against most Leishmania species, including those that cause cutaneous disease.
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Liposomal Amphotericin B for the Treatment of Visceral Leishmaniasis by Bern C, Adler-Moore J, Berenguer J, Boelaert M, den Boer M, Davidson RN, Figueras C, Gradoni L, Kafetzis DA, Ritmeijer K, Rosenthal E, Royce C, Russo R, Sundar S, Alvar J. Clin Infect Dis. 2006 Oct 1;43(7):917-24. Epub 2006 Aug 28.
During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit groups in East Africa. The public health community should work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs.
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In-vitro and in-vivo studies on a topical formulation of sitamaquine dihydrochloride for cutaneous leishmaniasis by Garnier T, Brown MB, Lawrence MJ, Croft SL. J Pharm Pharmacol. 2006 Aug;58(8):1043-54.
The efficacy of topical formulations of the 8-aminoquinoline, sitamaquine dihydrochloride, in both in vitro and in in-vivo models of cutaneous leishmaniasis is reported.
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Mechanisms of experimental resistance of Leishmania to miltefosine: Implications for clinical use by Perez-Victoria FJ, Sanchez-Canete MP, Seifert K, Croft SL, Sundar S, Castanys S, Gamarro F. Drug Resist Updat. 2006 Feb-Apr;9(1-2):26-39. Review.
Miltefosine (hexadecylphosphocholine, MIL), registered as Impavido®, has become the first oral drug for the treatment of visceral and cutaneous leishmanasis. MIL is a simple molecule, very stable, relatively safe and highly efficient in clinical trials. However, MIL requires a long treatment course (28 days) and has a long half-life (around 150 h), which might accelerate the emergence of drug resistance in case of inadequate use.
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Current scenario of drug development for leishmaniasis by Croft SL, Seifert K, Yardley V. Indian J Med Res. 2006 Mar; 123(3):399-410. Review.
As part of research to identify better treatments for VL and cutaneous leishmaniasis (CL), alternative and potentially cheaper formulations of amphotericin B, alklyphosphocholines other than miltefosine and improved formulations of paromomycin for CL have been identified. The process for discovery and development of new antileishmanials would also benefit from improved models, for example, transfected parasites, and non invasive methods of measuring parasite load in rodent models of infection.
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Drug resistance in leishmaniasis by Croft SL, Sundar S, Fairlamb AH. Clin Microbiol Rev. 2006 Jan;19(1):111-26.
Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. It is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy.
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In Vitro and In Vivo Interactions between Miltefosine and Other Antileishmanial Drugs by Seifert K, Croft SL. Antimicrob Agents Chemother. 2006 Jan;50(1):73-9.
The interaction of miltefosine with amphotericin B, sodium stibogluconate, paromomycin, and sitamaquine was assessed in vitro and additionally for the first three combinations in vivo.
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Situational analysis of leishmaniases research in Kenya by Tonui WK. Afr J Health Sci. 2006;13(1-2):7-21.
Leishmaniasis has been known to be endemic in parts of Kenya from as far back as early in the 20th century. Since 1980, the Kenya Medical Research Institute (KEMRI) has spearheaded research on leishmaniases research in Kenya focusing on various aspects including characterization of Leishmania species, biology, and ecology of sand fly vectors, development of biological strategies for sand fly control, identification of animal reservoirs, diagnosis, new treatment strategies, new chemotherapeutic agents, and vaccine-related studies.
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Chemotherapy in the Treatment and Control of Leishmaniasis by Alvar J, Croft S, Olliaro P. Adv. Parasitol. 2006; 61:223-74.
Drugs remain the most important tool for the treatment and control of both visceral and cutaneous leishmaniasis. Although there have been several advances in the past decade, with the introduction of new therapies by liposomal amphotericin, oral miltefosine and paromomycin (PM), these are not ideal drugs, and improved shorter duration, less toxic and cheaper therapies are required.
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