Affiliation:
1. Groupe de Recherche en Immunopathologie de la Leishmaniose, Laboratoire de Parasitologie, Faculté de Médecine, 06107 Nice Cedex 2,1 and
2. Virbac, BP 27, 06511 Carros Cedex,2France
Abstract
ABSTRACT
In the immunocompetent host, visceral leishmaniasis (VL) is a fatal disease if untreated. In immunosuppressed patients, VL is an opportunistic infection for which there is no effective treatment for relapses. Here we report on the long-term activity of orally administered hexadecylphosphocholine (HDPC) against established
Leishmania infantum
infection in BALB/c mice. HDPC is a synthetic phospholipid with antiproliferative properties that has been extensively studied for its cancerostatic activity. Its short-term leishmanicidal effects in mice recently infected with viscerotropic
Leishmania
species have been previously reported. First, we show that 5 days of oral therapy with HDPC (20 mg/kg of body weight/day) led to amastigote suppression in the liver and the spleen of 94 and 78%, respectively (versus 85 and 55% suppression by meglumine antimonate in the liver and spleen, respectively), in mice infected 6 weeks before treatment and examined 3 days after the end of treatment. These results demonstrate the short-term efficacy of HDPC against an established
Leishmania
infection. Next, the long-term efficacy of HDPC was examined. In HDPC-treated mice both the hepatic and splenic amastigote loads were significantly reduced (at least 89%) 10, 31, and 52 days after the end of the treatment. In the treated mice, the increase of the splenic load was significantly slower than that in the untreated mice, demonstrating that the HDPC-exerted inhibition of
Leishmania
growth persisted for at least 7 to 8 weeks. Orally administered HDPC—the safe doses and side effects of which are at least partially known—appears to be a promising candidate for the treatment of VL.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference56 articles.
1. Ten years of kala-azar in West Bengal. Part I. Did post-kala-azar dermal leishmaniasis initiate the outbreak in 24-Parganas?;Addy M.;Bull. W. H. O.,1992
2. AIDS and Leishmania infantum. New approaches for a new epidemiological problem.;Alvar J.;Clin. Dermatol.,1996
3. Aronson N. J. Jackson G. Wortmann and C. Oster. 1997. Sodium stibogluconate therapy for leishmaniasis: the experience of the american military 1989–1996 abstr. 374. Acta Parasitol. Turcica 21 (Suppl. 1) : 177.
4. Molecular and cellular effects of hexadecylphosphocholine (Miltefosine) in human myeloid leukaemic cell lines.;Beckers T.;Eur. J. Cancer,1994
5. Ben Said M. A. Mili F. Amri and H. Kharrat. 1997. Resistance to N -methylglucamine in tunisian visceral leishmaniasis children abstr. 395. Acta Parasitol. Turcica 21 (Suppl. 1) : 184.
Cited by
62 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献