Population genetic analysis of the negative selection of chloroquine resistant Plasmodium falciparum parasites in the absence of antimalarial pressure

无抗疟压力下耐氯喹恶性疟原虫阴性选择的群体遗传分析

• 批准号: 15590375
• 负责人: MITA Toshihiro
• 金额: $ 2.3万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590375/
• 关键词: Plasmodium falciparum; chloroquine; resistance; selection; fitness; pfcrt; pfmdr1; 薬剤圧; cost; 淘汰

In Malawi, the first line drug for treatment of P.falciparum was officially changed from chloroquine to sulfadoxine/pyrimethamine in 1993 because of increasing treatment failure rates that eventually reached 80 %. We previously conducted two drug efficacy surveys in 1998 and 2000 in Salima district in Malawi and found a significant recovery of chloroquine sensitivity both in vitro (3 %) and in vivo (9 %). Concomitant with the recovery of chloroquine sensitivity, the prevalence of the K76T mutation was observed to be substantially lower (9%) than in other African countries where chloroquine use has continued (41-81%). We evidenced that an increased prevalence of the wild type pfcrt haplotype is implicated in the recent recovery of chloroquine sensitivity in Malawi since chloroquine withdrawal. In contrast, we did not see any haplotypes consistent with a K76T→K76 back mutation. Reintroduction of chloroquine as a component drug of combination regimes may be a possible option in places where the complete disappearance of resistant parasites is confirmed.

在马拉维，由于治疗失败率提高，最终达到80％的治疗率，1993年从氯喹进行治疗的第一线药物正式从氯喹转换为磺胺毒素/吡胺甲胺。我们以前在1998年和2000年在马拉维的萨利玛（Salima）区进行了两项药物效率调查，并发现体外（3％）和体内（9％）的氯喹敏感性都显着恢复。与氯喹敏感性的恢复同时，观察到K76T突变的患病率大大低于（9％）（9％），而在其他非洲国家则持续使用氯喹（41-81％）。我们证明，自从氯喹退出以来，马拉维最近在马拉维的氯喹敏感性中恢复了野生型PFCRT单倍型的增加。相反，我们没有看到与K76T→K76背部突变一致的任何单倍型。在确认抗性寄生虫完全消失的地方，可能是可能的选择，将氯喹重新引入氯喹作为组合药物。

项目成果

Bwijo B, Mita T, et al.: "High prevalence of quintuple mutant dhps/dhfr genes in Plasmodium falciparum infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi"Acta Trop. 85(3). 363-373 (2003)

Bwijo B、Mita T 等人：“在马拉维引入磺胺多辛和乙胺嘧啶作为一线治疗七年后，恶性疟原虫感染中五重突变 dhps/dhfr 基因的高流行”Acta Trop。

Mita T, et al.: "Recovery of chlo+roquine sensitivity and low prevalence of pfcrt K76T in Plasmodium falciparum following withdrawal of chlorocguine use in Malawi"Am J Trop Med Hyg. 68(4). 413-415 (2003)

Mita T 等人：“在马拉维停止使用氯喹后，恶性疟原虫中氯喹敏感性的恢复和 pfcrt K76T 的低流行率”Am J Trop Med Hyg。

Mita T, et al.: "Expansion of wild type allele rather than back mutation in Pfcrt explains the recent recovery of chloroquine sensitivity of Plasmodium falciparum in Malawi"Mol Biochem Parasitol. (In print). (2004)

Mita T 等人：“野生型等位基因的扩展而不是 Pfcrt 中的回复突变解释了马拉维恶性疟原虫氯喹敏感性最近的恢复”Mol Biochem Parasitol。