Anti-relapse activity of mirincamycin in the Plasmodium cynomolgi sporozoite-infected Rhesus monkey model

Malaria Journal

Research

David Saunders¹  Paktiya Teja-isavadharm¹  Montip Gettayacamin²  Colin Ohrt³  Jonathan Berman³  Susan Fracisco³  Qigui Li³  Victor Melendez³  Lisa Xie³ 

[1] Department of Immunology and Medicine, United States Army Medical Component – Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand;Department of Veterinary Medicine, United States Army Medical Component – Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand;Walter Reed Army Institute of Research, Silver Spring, MD, USA;

关键词: Malaria;    P. vivax;    Hypnozoites;    Relapse;    Mirincamycin;    Rhesus monkey;   

DOI  :  10.1186/1475-2875-13-409

 received in 2014-01-24, accepted in 2014-05-20,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundMirincamycin is a close analog of the drug clindamycin used to treat Plasmodium falciparum blood stages. The clinical need to treat Plasmodium vivax dormant liver stages and prevent relapse with a drug other than primaquine led to the evaluation of mirinicamycin against liver stages in animals.Methodscis- mirinicamycin and trans-mirinicamycin were evaluated as prophylaxis against early liver stages of Plasmodium berghei in mice and as antirelapse hypnozoiticides against Plasmodium cynomolgi in the Rhesus monkey (Macaca mulatta).ResultsMirincamycin was very effective against early liver stages of P. berghei in mice: both cis and trans enantiomers were 90-100% causally prophylactic at 3.3 mg/kg/day for 3 days orally. Both cis and trans mirincamycin, however, failed to kill dormant liver stages (hypnozoites) in the P. cynomolgi infected Rhesus monkey, the only preclinical hypnozoite model. Mirincamycin enantiomers at 80 mg/kg/day for 7 days orally, a dose that generated exposures comparable to that seen clinically, did not prevent relapse in any of four monkeys.ConclusionsAlthough efficacy against early liver stages of P. berghei was thought to correlate with anti-hypnozoite activity in primates, for mirincamycin, at least, there was no correlation. The negative P. cynomolgi hypnozoite data from Rhesus monkeys indicates that mirincamycin is unlikely to have potential as a clinical anti-relapse agent.

【 授权许可】

Unknown   
© Fracisco et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.