Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum
Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum
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DOI：
10.1098/rspb.2015.3038
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发表时间：
2016-03-16
影响因子：
4.7
通讯作者：
Udhayakumar, Venkatachalam
中科院分区：
文献类型：
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作者：
Bushman, Mary;Morton, Lindsay;Udhayakumar, Venkatachalam
疟疾寄生虫恶性疟原虫的感染通常包括多种菌株，特别是在经常发生传染性蚊虫叮咬的高传播地区。然而，对混合菌株感染的动力学知之甚少，特别是共享宿主的菌株是否竞争或独立生长。药物敏感菌株和耐药菌株之间的竞争，如果发生，可能是耐药性传播的关键决定因素。我们分析了来自安哥拉、加纳和坦桑尼亚的1341例儿童恶性疟原虫感染，发现了混合菌株感染竞争的令人信服的证据：总体寄生虫密度并没有随着额外菌株的增加而增加，在竞争对手存在的情况下，单个氯喹敏感（CQS）和氯喹耐药（CQR）菌株的密度降低。我们还发现，CQR菌株表现出较低的密度相比，CQS菌株（在没有氯喹），这可能是在许多国家的氯喹作为一线治疗退休后观察到的氯喹耐药性下降的基础。我们的观察结果支持宿主内竞争在抗药性疟疾演变中的关键作用。在高传播地区，疟疾控制和耐药性管理工作可能会受到混合菌株感染竞争效应的极大帮助或阻碍。考虑内主机动态可能会刺激新的战略，以尽量减少阻力，同时最大限度地提高控制措施的好处的发展。
Infections with the malaria parasite Plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analysed 1341 P. falciparum infections in children from Angola, Ghana and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) strains were reduced in the presence of competitors. We also found that CQR strains exhibited low densities compared with CQS strains (in the absence of chloroquine), which may underlie observed declines of chloroquine resistance in many countries following retirement of chloroquine as a first-line therapy. Our observations support a key role for within-host competition in the evolution of drug-resistant malaria. Malaria control and resistance-management efforts in high-transmission regions may be significantly aided or hindered by the effects of competition in mixed-strain infections. Consideration of within-host dynamics may spur development of novel strategies to minimize resistance while maximizing the benefits of control measures.