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Misclassification of drug failure in Plasmodium falciparum clinical trials in southeast Asia.

ABSTRACT: 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.

SUBMITTER: Juliano JJ

PROVIDER: S-EPMC2761972 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Misclassification of drug failure in Plasmodium falciparum clinical trials in southeast Asia.

Juliano Jonathan J JJ Ariey Frederic F Sem Rithy R Tangpukdee Noppadon N Krudsood Srivicha S Olson Carol C Looareesuwan Sornchai S Rogers William O WO Wongsrichanalai Chansuda C Meshnick Steven R SR

The Journal of infectious diseases 20090801 4

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 trac ...[more]

PMID: 19591576

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