Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.
Malar J. 2011 May 14;10:123. doi: 10.1186/1475-2875-10-123.
Drug resistance contributes to the global malaria burden. Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxine-pyrimethamine (SP).
The study assessed the frequency of SP resistance-conferring polymorphisms in Plasmodium falciparum-positive samples from two clinical studies in Lambaréné. Their role on treatment responses and transmission potential was studied in an efficacy open-label clinical trial with a 28-day follow-up in 29 children under five with uncomplicated malaria.
SP was well tolerated by all subjects in vivo. Three subjects were excluded from per-protocol analysis. PCR-corrected, 12/26 (46%) achieved an adequate clinical and parasitological response, 13/26 (50%) were late parasitological failures, while 1/26 (4%) had an early treatment failure, resulting in early trial discontinuation. Of 106 isolates, 98 (92%) carried the triple mutant dhfr haplotype. Three point mutations were found in dhps in a variety of haplotypic configurations. The 437G + 540E double mutant allele was found for the first time in Gabon.
There is a high prevalence of dhfr triple mutant with some dhps point mutations in Gabon, in line with treatment failures observed, and molecular markers of SP resistance should be closely monitored.
耐药性是全球疟疾负担的一个重要因素。恶性疟原虫二氢叶酸还原酶（dhfr）和二氢蝶酸合成酶（dhps）的多态性导致对磺胺多辛-乙胺嘧啶（SP）的耐药性。
本研究评估了来自兰巴雷内的两项临床研究中，疟原虫阳性样本中 SP 耐药相关多态性的频率。在一项为期 28 天、29 名五岁以下患有无并发症疟疾的儿童参与的开放标签临床疗效试验中，研究了它们对治疗反应和传播潜力的作用。
所有受试者在体内均能耐受 SP。3 名受试者因不符合方案而被排除在分析之外。PCR 校正后，26 例中有 12 例（46%）获得了充分的临床和寄生虫学反应，26 例中有 13 例（50%）为晚期寄生虫学失败，而 26 例中有 1 例（4%）为早期治疗失败，导致早期试验中止。在 106 株分离株中，98 株（92%）携带三重突变 dhfr 单倍型。在各种单倍型结构中发现了 dhps 的 3 个点突变。437G + 540E 双突变等位基因首次在加蓬发现。
在加蓬，dhfr 三重突变与 dhps 中的一些点突变同时存在，与观察到的治疗失败相一致，因此应密切监测 SP 耐药的分子标记。
