Mutations that mediate resistance of Plasmodium falciparum to aminoquinoline antimalarials are selected by prior drug use and may alter parasite fitness, but associations with clinical presentations are uncertain. We evaluated genotypes in samples from a case-control study of determinants of severe malaria in Ugandan children 4 months to 10 years of age. We studied 274 cases with severe malaria matched by age and geography to 275 uncomplicated malaria controls and 179 asymptomatic parasitemic controls. The overall prevalence of mutations of interest (considering mixed results as mutant) was 67.0% for PfCRT K76T, 8.5% for PfMDR1 N86Y, 71.5% for PfMDR1 Y184F, and 14.7% for PfMDR1 D1246Y. Compared to asymptomatic controls, the odds of mutant PfCRT 76T were lower for uncomplicated (odds ratio, 0.42 [95% confidence interval, 0.24 to 0.72]; P < 0.001) or severe (0.56 [0.32 to 0.97]; P = 0.031) malaria; the odds of mutant PfMDR1 86Y were lower for uncomplicated (0.33 [0.16 to 0.65]; P < 0.001) or severe (0.21 [0.09 to 0.45]; P < 0.001) malaria; and the odds of mutant PfMDR1 1246Y were higher for uncomplicated (1.83 [0.90 to 3.98]; P = 0.076) or severe (2.06 [1.01 to 4.55]; P = 0.033) malaria. The odds of mutant PfMDR1 184F were lower in severe than asymptomatic (0.59 [0.37 to 0.92]; P = 0.016) or uncomplicated (0.61 [0.41 to 0.90]; P = 0.009) malaria. Overall, the PfCRT 76T and PfMDR1 86Y mutations were associated with decreased risk of symptomatic malaria, PfMDR1 1246Y was associated with increased risk of symptomatic malaria, and PfMDR1 184F was associated with decreased risk of severe malaria. These results offer insights into parasite genotypes in children with different presentations, although the basis for the identified associations is likely complex.

中文翻译：

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乌干达氨喹啉耐药基因型与恶性疟原虫感染临床表现之间的关联。

介导恶性疟原虫抗性的突变与氨基喹啉抗疟药是通过先前的药物使用选择的，可能会改变寄生虫的适应性，但与临床表现的关联尚不确定。我们评估了来自乌干达 4 个月至 10 岁儿童严重疟疾决定因素的病例对照研究样本中的基因型。我们研究了 274 例与年龄和地理相匹配的严重疟疾病例，以及 275 例无并发症的疟疾对照和 179 例无症状寄生虫对照。PfCRT K76T 的感兴趣突变的总体流行率（将混合结果视为突变）为 67.0%，PfMDR1 N86Y 为 8.5%，PfMDR1 Y184F 为 71.5%，PfMDR1 D1246Y 为 14.7%。与无症状对照组相比，突变型 PfCRT 76T 的几率较低（优势比，0.42 [95% 置信区间，0.24 至 0.72]；P< 0.001) 或重度 (0.56 [0.32 至 0.97]；P = 0.031) 疟疾；对于单纯性（0.33 [0.16 至 0.65]； P < 0.001）或严重（0.21 [0.09 至 0.45]；P < 0.001）疟疾，突变 PfMDR1 86Y 的几率较低；对于非复杂性（1.83 [0.90 至 3.98]； P = 0.076）或严重（2.06 [1.01 至 4.55]；P = 0.033）疟疾，突变 PfMDR1 1246Y 的几率更高。突变 PfMDR1 184F 的几率低于无症状（0.59 [0.37 至 0.92]；P = 0.016）或无并发症（0.61 [0.41 至 0.90]；P= 0.009) 疟疾。总体而言，PfCRT 76T 和 PfMDR1 86Y 突变与症状性疟疾风险降低相关，PfMDR1 1246Y 与症状性疟疾风险增加相关，PfMDR1 184F 与严重疟疾风险降低相关。这些结果提供了对具有不同表现的儿童寄生虫基因型的见解，尽管确定的关联的基础可能很复杂。