Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria
Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria
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DOI：
10.4269/ajtmh.2003.69.558
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发表时间：
2003-11-01
影响因子：
3.3
通讯作者：
Plowe, CV
中科院分区：
文献类型：
--
作者：
Djimdé, AA;Doumbo, OK;Plowe, CV
疟疾流行地区的居民有时无需药物治疗即可自发清除恶性疟原虫感染，这意味着免疫等宿主因素在清除过程中发挥着重要作用。宿主因素也可能有助于清除对治疗药物有抗药性的寄生虫。氯喹耐药性是由恶性疟原虫氯喹耐药性转运蛋白 (pfcrt) 基因点突变引起的。我们调查了接受氯喹治疗的患者体内携带关键氯喹耐药性 PfCRT 突变 K76T 的疟疾寄生虫的清除情况。我们发现清除这些耐药寄生虫的能力在很大程度上取决于年龄（流行地区保护性免疫的最佳替代指标），这表明宿主免疫在清除耐药性恶性疟原虫感染中发挥着关键作用。对能够清除耐药寄生虫和不能清除耐药寄生虫的受试者进行年龄调整的比较，为识别负责抵抗疟疾的保护性免疫力的宿主免疫和遗传因素提供了一种新的表型。
Residents of malaria-endemic areas sometimes spontaneously clear Plasmodium falciparum infection without drug treatment, implying an important role for host factors such as immunity in this clearance. Host factors may also contribute to clearance of parasites resistant to a treatment drug. Chloroquine resistance is caused by point mutations in P. falciparum chloroquine resistance transporter (pfcrt) gene. We investigated the clearance of malaria parasites carrying the key chloroquine resistance-conferring PfCRT mutation K76T in patients treated with chloroquine. We found that the ability to clear these resistant parasites is strongly dependent on age (the best surrogate for protective immunity in endemic areas), suggesting that host immunity plays a critical role in the clearance of resistant P. falciparum infections. Age-adjusted comparison of subjects able to clear resistant parasites and those unable to do so provides a new phenotype for identifying host immune and genetic factors responsible for protective immunity against malaria.