Evaluation of parasite subpopulations and genetic diversity of the msp1, msp2 and glurp genes during and following artesunate monotherapy treatment of Plasmodium falciparum malaria in Western Cambodia

Malaria Journal

Research

Chanthap Lon¹  Youry Se¹  Darapiseth Sea¹  Charlotte A Lanteri²  Sabaithip Sriwichai²  Douglas S Walsh²  Jessica Manning²  Kingkan Pidtana²  Saowaluk Wongarunkochakorn²  David L Saunders²  Delia Bethell²  Stuart D Tyner²  Sittidech Surasri²  Panita Gosi²  Mark M Fukuda²  Michele Spring²  Mengchuor Char³ 

[1] Armed Forces Research Institute of Medical Science (AFRIMS), Phnom Penh, Cambodia;Department of Immunology and Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Bangkok, Thailand;National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia;

关键词: Malaria;    Plasmodium falciparum;    Cambodia;    Genotype;    Artesunate;    msp1;    msp2;    glurp;   

DOI  :  10.1186/1475-2875-12-403

 received in 2013-07-25, accepted in 2013-11-04,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundDespite widespread coverage of the emergence of artemisinin resistance, relatively little is known about the parasite populations responsible. The use of PCR genotyping around the highly polymorphic Plasmodium falciparum msp1, msp2 and glurp genes has become well established both to describe variability in alleles within a population of parasites, as well as classify treatment outcome in cases of recurrent disease. The primary objective was to assess the emergence of minority parasite clones during seven days of artesunate (AS) treatment in a location with established artemisinin resistance. An additional objective was to investigate whether the classification of clinical outcomes remained valid when additional genotyping was performed.MethodsBlood for parasite genotyping was collected from 143 adult patients presenting with uncomplicated falciparum malaria during a clinical trial of AS monotherapy in Western Cambodia. Nested allelic type-specific amplification of the genes encoding the merozoite surface proteins 1 and 2 (msp1 and msp2) and the glutamate-rich protein (glurp) was performed at baseline, daily during seven days of treatment, and again at failure. Allelic variants were analysed with respect to the size of polymorphisms using Quantity One software to enable identification of polyclonal infections.ResultsConsiderable variation of msp2 alleles but well-conserved msp1 and glurp were identified. At baseline, 31% of infections were polyclonal for one or more genes. Patients with recurrent malaria were significantly more likely to have polyclonal infections than patients without recurrence (seven of nine versus 36 of 127, p = 0.004). Emergence of minority alleles during treatment was detected in only one of twenty-three cases defined as being artemisinin resistant. Moreover, daily genotyping did not alter the final outcome classification in any recurrent cases.ConclusionsThe parasites responsible for artemisinin-resistant malaria in a clinical trial in Western Cambodia comprise the dominant clones of acute malaria infections rather than minority clones emerging during treatment. Additional genotyping during therapy was not beneficial. Disproportionately high rates of polyclonal infections in cases of recurrence suggest complex infections lead to poor treatment outcomes. Current research objectives should be broadened to include identification and follow-up of recurrent polyclonal infections so as to define their role as potential agents of emerging resistance.

【 授权许可】

Unknown   
© Gosi et al.; licensee BioMed Central Ltd. 2013. 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 cited.