Misclassification of Drug Failure in Plasmodium falciparum Clinical Trials in Southeast Asia

被引：21

作者：

Juliano, Jonathan J. ^{[2
]}

Ariey, Frederic ^{[5
]}

Sem, Rithy ^{[5
]}

Tangpukdee, Noppadon ^{[6
]}

Krudsood, Srivicha ^{[6
]}

Olson, Carol ^{[3
]}

Looareesuwan, Sornchai ^{[6
]}

Rogers, William O. ^{[4
]}

Wongsrichanalai, Chansuda ^{[4
]}

Meshnick, Steven R. ^{[1
]}

机构：

[1] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Sch Med, Div Infect Dis, Chapel Hill, NC 27599 USA

[3] Immtech Pharmaceut Inc, Vernon Hills, IL USA

[4] Naval Med Res Unit 2, Jakarta, Indonesia

[5] Inst Pasteur Cambodge, Phnom Penh, Cambodia

[6] Mahidol Univ, Hosp Trop Dis, Fac Trop Med, Bangkok 10700, Thailand

来源：

JOURNAL OF INFECTIOUS DISEASES | 2009年 / 200卷 / 04期

关键词：

HETERODUPLEX TRACKING ASSAY; POPULATION-DYNAMICS; INFECTIONS;

D O I：

10.1086/600892

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Most trials of antimalarials occur in areas in which reinfections are possible. For Plasmodium falciparum, reinfections are distinguished from recrudescences by polymerase chain reaction analysis of 3 polymorphic genes. However, the validity of this approach has never been rigorously tested. We tested for misclassification in 6 patients from clinical trials in Thailand and Cambodia who were classified as being reinfected by the standard polymerase chain reaction protocol. Using heteroduplex tracking assays and direct DNA sequencing, we found that 5 (83%) of 6 patients were misclassified. Misclassification in this manner overestimates the efficacy of antimalarials and delays the recognition of decreasing therapeutic efficacy, thus delaying potential changes in policy.

引用

页码：624 / 628

页数：5

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