Impact of transmission intensity on the accuracy of genotyping to distinguish recrudescence from new infection in antimalarial clinical trials

被引:59
作者
Greenhouse, Bryan
Dokomajilar, Christian
Hubbard, Alan
Rosenthal, Philip J.
Dorsey, Grant
机构
[1] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA
[2] Univ Calif Berkeley, Sch Publ Hlth, Grp Biostat, Berkeley, CA 94720 USA
关键词
D O I
10.1128/AAC.00159-07
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Antimalarial clinical trials use genotyping techniques to distinguish new infection from recrudescence. In areas of high transmission, the accuracy of genotyping may be compromised due to the high number of infecting parasite strains. We compared the accuracies of genotyping methods, using up to six genotyping markers, to assign outcomes for two large antimalarial trials performed in areas of Africa with different transmission intensities. We then estimated the probability of genotyping misclassification and its effect on trial results. At a moderate-transmission site, three genotyping markers were sufficient to generate accurate estimates of treatment failure. At a high-transmission site, even with six markers, estimates of treatment failure were 20% for amodiaquine plus artesunate and 17% for artemether-lumefantrine, regimens expected to be highly efficacious. Of the observed treatment failures for these two regimens, we estimated that at least 45% and 35%, respectively, were new infections misclassified as recrudescences. Increasing the number of genotyping markers improved the ability to distinguish new infection from recrudescence at a moderate-transmission site, but using six markers appeared inadequate at a high-transmission site. Genotyping-adjusted estimates of treatment failure from high-transmission sites may represent substantial overestimates of the true risk of treatment failure.
引用
收藏
页码:3096 / 3103
页数:8
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