High resistance of Plasmodium falciparum to sulphadoxine/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at Codon 581.
High resistance of Plasmodium falciparum to sulphadoxine/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at Codon 581.
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DOI：
10.1371/journal.pone.0004569
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Chandramohan, Daniel
中科院分区：
文献类型：
--
作者：
Gesase, Samwel;Gosling, Roly D.;Hashim, Ramadhan;Ord, Rosalynn;Naidoo, Inbarani;Madebe, Rashid;Mosha, Jacklin F.;Joho, Angel;Mandia, Victor;Mrema, Hedwiga;Mapunda, Ephraim;Savael, Zacharia;Mosha, Frank W.;Greenwood, Brian;Roper, Cally;Chandramohan, Daniel
磺胺二甲基乙胺(SP)是一种广泛用于治疗无并发症疟疾的药物，建议用于妊娠期疟疾的间歇预防治疗，目前正在研究用于婴儿疟疾间歇预防治疗(IPTI)。坦桑尼亚东北部报告了与寄生虫基因突变有关的对SP的高水平抗药性。这项研究比较了SP在6-59个月有症状的无并发症疟疾儿童和2-10个月无症状的婴儿中的体内疗效。6-59个月大的有症状儿童使用开放标记的单臂(SP)标准体内28天WHO抗疟疗效方案，2-10个月无症状的婴儿使用改进的方案。由于失败率高，登记提前停止(有症状的87人，无症状的25人)。检测复发、再感染的分子标志物和耐药标志物，并对寻找581G DHPS突变的文献进行综述。在有症状的儿童中，经聚合酶链式反应纠正的早期治疗失败率为38.8%(95%可信区间为26.8-50.8)，到第28天总的治疗失败率为82.2%(95%可信区间为72.5-92.0)。在无症状和有症状的儿童中，治疗失败的发生率没有显著差异。96%的样本携带有dhfr基因第51、59和108密码子突变的寄生虫，63%的样本携带437和540密码子的双重突变。55%的人携带第三个突变，并在dhps基因的第581密码子增加了一个突变。这种三重：三重单倍型可能与早期治疗失败有关。在坦桑尼亚北部，SP是一种失败的治疗药物，其预防作用值得怀疑。这项研究发现了一种新的寄生虫突变组合，可能与增加和更早的失败有关。ClinicalTrials.gov NCT00361114
Sulphadoxine-pyrimethamine (SP) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy, is being investigated for intermittent preventive treatment of malaria in infants (IPTi). High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes. This study compared the in vivo efficacy of SP in symptomatic 6–59 month children with uncomplicated malaria and in asymptomatic 2–10 month old infants. An open label single arm (SP) standard 28 day in vivo WHO antimalarial efficacy protocol was used in 6 to 59 months old symptomatic children and a modified protocol used in 2 to 10 months old asymptomatic infants. Enrolment was stopped early (87 in the symptomatic and 25 in the asymptomatic studies) due to the high failure rate. Molecular markers were examined for recrudescence, re-infection and markers of drug resistance and a review of literature of studies looking for the 581G dhps mutation was carried out. In symptomatic children PCR-corrected early treatment failure was 38.8% (95% CI 26.8–50.8) and total failures by day 28 were 82.2% (95% CI 72.5–92.0). There was no significant difference in treatment failures between asymptomatic and symptomatic children. 96% of samples carried parasites with mutations at codons 51, 59 and 108 in the dhfr gene and 63% carried a double mutation at codons 437 and 540. 55% carried a third mutation with the addition of a mutation at codon 581 in the dhps gene. This triple: triple haplotype maybe associated with earlier treatment failure. In northern Tanzania SP is a failed drug for treatment and its utility for prophylaxis is doubtful. The study found a new combination of parasite mutations that maybe associated with increased and earlier failure. ClinicalTrials.gov NCT00361114
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作者：
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