Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy, and Odonto-Stomatology, University of Science, Techniques and Technology, Bamako, Mali.
J Infect Dis. 2013 Feb 1;207(3):520-7. doi: 10.1093/infdis/jis691. Epub 2012 Nov 16.
The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13.
We conducted prospective quinine efficacy studies in 2 villages, Kollé and Faladié, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing.
Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment.
This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field.
疟原虫对奎宁的耐药机制尚不清楚。体外数量性状基因座图谱表明，预测的疟原虫钠离子-氢交换蛋白（pfnhe-1）位于 13 号染色体上与耐药相关。
我们在马里的科莱和法拉迪埃两个村庄进行了前瞻性奎宁疗效研究。需要静脉内治疗的临床疟疾病例采用标准剂量的奎宁进行治疗，并随访 28 天。采用改良的世界卫生组织方案对治疗结果进行分类。利用寄生虫多态性的分子标记来区分复发性寄生虫和新感染的寄生虫。通过直接测序确定奎宁治疗前后 pfne-1 ms4760-1 在寄生虫中的流行率。
共有 163 名患者入组并成功随访。未经分子校正时，总临床和寄生虫学适当反应（ACPR）的平均值为 50.3%（n = 163）。经过聚合酶链反应校正以说明新感染的情况后，校正后的 ACPR 为 100%。ms4760-1 的流行率显著增加，从奎宁治疗前的 26.2%（n = 107）增加到治疗后的 46.3%（n = 54）（P =.01）。在磺胺多辛-乙胺嘧啶对照研究中，治疗前后 ms4760-1 的流行率相似。
本研究支持 pfne-1 在现场降低疟原虫对奎宁的敏感性中起作用。
