Ndounga Mathieu, Tahar Rachida, Basco Leonardo K, Casimiro Prisca N, Malonga David A, Ntoumi Francine
Laboratoire de Pharmacologie, Centre d'Etudes sur les Ressources Végétales, Brazzaville, Congo.
Trop Med Int Health. 2007 Oct;12(10):1164-71. doi: 10.1111/j.1365-3156.2007.01904.x.
To test the efficacy of sulfadoxine-pyremethamine (SP) monotherapy and establish the prevalence of mutations in dhfr and dhps in Brazzaville, Congo.
We recruited 97 patients aged 6-59 months with uncomplicated malaria who attended Tenrikyo public health centre. Eighty-three were followed until day 28. SP efficacy was determined by the WHO 28-day test and analysis of mutations in the Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes.
There were seven (8.4%) early treatment failures, 23 late treatment failures (27.7%), nine (10.8%) late parasitological failures and 44 (53%) adequate clinical and parasitological responses (ACPR). After polymerase chain reaction (PCR) analysis of 64 available samples, the corrected results there were 44 (68.8%) ACPR and 19 recrudescent cases (31.2%). Approximately, 97.5% of samples bore the Asn51Ile mutation, 66.2% the Cys59Arg mutation and 98.8% the Ser108Asn mutation. Mutations of dhps at positions 437 (Ala-Gly) and 436 (Ser-Ala) were found in 85% and 12.5% of samples. Quadruple mutations (pfdhfr triple mutations in codons 51, 59 and 108+ pfdhps mutation in 437) were found in 42 samples (52.5%) and associated with treatment failures.
This high level of treatment failures and mutations in both genes calls for the urgent application of the new policy for malaria treatment to delay the spread of SP resistance.
检测周效磺胺-乙胺嘧啶（SP）单药治疗的疗效，并确定刚果布拉柴维尔二氢叶酸还原酶（dhfr）和二氢蝶酸合酶（dhps）的突变率。
我们招募了97名6至59个月大、患有非复杂性疟疾的患者，他们在天理教公共卫生中心就诊。其中83名患者随访至第28天。SP疗效通过世卫组织28天试验以及对恶性疟原虫二氢叶酸还原酶（pfdhfr）和二氢蝶酸合酶（pfdhps）基因的突变分析来确定。
有7例（8.4%）早期治疗失败，23例晚期治疗失败（27.7%），9例（10.8%）晚期寄生虫学失败，44例（53%）有充分的临床和寄生虫学反应（ACPR）。对64份可用样本进行聚合酶链反应（PCR）分析后，校正结果显示有44例（68.8%）ACPR和19例复发病例（31.2%）。大约97.5%的样本携带Asn51Ile突变，66.2%携带Cys59Arg突变，98.8%携带Ser108Asn突变。在85%和12.5%的样本中发现了dhps第437位（Ala-Gly）和第436位（Ser-Ala）的突变。在42个样本（52.5%）中发现了四重突变（pfdhfr第51、59和108位密码子的三重突变 + pfdhps第437位突变），且与治疗失败相关。
这种高水平的治疗失败以及两个基因的突变，要求紧急应用新的疟疾治疗政策，以延缓SP耐药性的传播。
