Misclassification of Drug Failure in Plasmodium falciparum Clinical Trials in Southeast Asia
Misclassification of Drug Failure in Plasmodium falciparum Clinical Trials in Southeast Asia
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DOI：
10.1086/600892
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发表时间：
2009-08-15
影响因子：
6.4
通讯作者：
Meshnick, Steven R.
中科院分区：
文献类型：
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作者：
Juliano, Jonathan J.;Ariey, Frederic;Meshnick, Steven R.
大多数抗疟药物试验都是在可能再次感染的地区进行的。对于恶性疟原虫，通过聚合酶链反应分析3个多态性基因来区分再感染和复发。然而，这种方法的有效性从未得到严格的检验。我们在泰国和柬埔寨的临床试验中对6名患者进行了错误分类测试，这些患者被标准聚合酶链反应方案归类为再次感染。使用异源双链追踪分析和直接DNA测序，我们发现6例患者中有5例（83%）被错误分类。以这种方式的错误分类高估了抗疟药物的疗效，并延迟了对疗效下降的认识，从而延迟了政策的潜在变化。
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.