Validation of a simplified method for using molecular markers to predict sulfadoxine-pyrimethamine treatment failure in African children with falciparum malaria
Validation of a simplified method for using molecular markers to predict sulfadoxine-pyrimethamine treatment failure in African children with falciparum malaria
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DOI：
10.4269/ajtmh.2003.69.247
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发表时间：
2003-09-01
影响因子：
3.3
通讯作者：
Dorsey, G
中科院分区：
文献类型：
--
作者：
Kyabayinze, D;Cattamanchi, A;Dorsey, G
监测恶性疟原虫二氢叶酸还原酶（DHFR）和二氢蝶酸合成酶（DHPS）的关键突变的分子标志物已被提出作为预测磺胺嘧啶/乙胺嘧啶（SP）治疗结果在非洲的一种手段。本研究评估了在乌干达坎帕拉用SP治疗无并发症疟疾的儿童中DHFR和DHPS突变与标准化临床结果之间的关联。两种突变（DHFR Asn-108和Ile-51）太常见，无法作为有用的预测因子。其他三个突变（DHFR Arg-59，DHPS Gly-437和DHPS Glu-540）与14天后的临床治疗失败相关，尽管相关性不显著。当随访延长至28天，并使用基因分型来区分复发和新感染时，相关性显著加强。DHFR Arg-59和DHPS Glu-540突变的存在与临床治疗失败的相关性最强（比值比10.7，P = 0.009）。这些结果支持了先前提出的基于这两种突变的患病率预测临床结果的方法。
Surveillance of molecular markers for key mutations in Plasmodhon falciparton dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) has been proposed as a means of predicting sulfadoxine/pyrimethamine (SP) treatment outcomes in Africa. This study assessed the association between DHFR and DHPS mutations and standardized clinical outcomes in children treated with SP for uncomplicated malaria in Kampala, Uganda. Two mutations (DHFR Asn-108 and Ile-51) were too common to be useful predictors. Three other mutations (DHFR Arg-59, DHPS Gly-437, and DHPS Glu-540) were associated with clinical treatment failure after 14 days, although associations were not significant. When follow-up was extended to 28 days and genotyping was used to distinguish recrudescence from new infections, associations were significantly strengthened. The presence of both the DHFR Arg-59 and DHPS Glu-540 mutations had the strongest association with clinical treatment failure (odds ratio 10.7, P = 0.009). These results support a previously proposed method of predicting clinical outcomes based on the prevalence of these two mutations.