Emergence of a dhfr mutation conferring high-level drug resistance in Plasmodium falciparum populations from southwest Uganda
Emergence of a dhfr mutation conferring high-level drug resistance in Plasmodium falciparum populations from southwest Uganda
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DOI：
10.1086/587845
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发表时间：
2008-06-01
影响因子：
6.4
通讯作者：
Roper, Cally
中科院分区：
文献类型：
--
作者：
Lynch, Caroline;Pearce, Richard;Roper, Cally
恶性疟原虫编码二氢叶酸还原酶(DHFR)的基因S108N、C59R和N51I突变导致对乙胺嘧啶的耐药性，在非洲很常见。然而，赋予高水平抗药性的I164L突变很少见。2005年，我们在乌干达西南部卡巴莱区的51名疟疾患者样本中发现，I164L突变的患病率为14%，同年在邻近的鲁昆吉里地区的72名疟疾患者中，I164L突变的患病率为4%。2002-2004年对乌干达6个地点的监测报告了1例感染I164L突变的病例，该突变也在乌干达西南部，这表明这是一个区域热点。I164L突变的空间聚集性和不断增加的流行率表明该突变的局部传播。需要进行有针对性的监测，以确认I164L突变的传播程度，并监测I164L对抗叶酸间歇预防性治疗患有恶性疟疾的孕妇和/或婴儿的疗效的影响。
The S108N, C59R, and N51I mutations in the Plasmodium falciparum gene that encodes dihydrofolate reductase, dhfr, confer resistance to pyrimethamine and are common in Africa. However, the I164L mutation, which confers high-level resistance, is rarely seen. We found a 14% prevalence of the I164L mutation among a sample of 51 patients with malaria in Kabale District in southwest Uganda in 2005 and a 4% prevalence among 72 patients with malaria in the neighboring district of Rukungiri during the same year. Surveillance at 6 sites across Uganda during 2002-2004 reported a single case of infection involving an I164L mutant, also in the southwest, suggesting that this is a regional hot spot. The spatial clustering and increasing prevalence of the I164L mutation is indicative of local transmission of the mutant. Targeted surveillance is needed to confirm the extent of the spread of the I164L mutation and to monitor the impact of I164L on the efficacy of antifolates for intermittent preventive treatment of pregnant women and/or infants with falciparum malaria.