Chemotherapy, within-host ecology and the fitness of drug-resistant malaria parasites.
Chemotherapy, within-host ecology and the fitness of drug-resistant malaria parasites.
复制标题
DOI：
10.1111/j.1558-5646.2010.01068.x
复制
发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Read AF
中科院分区：
文献类型：
--
作者：
Huijben S;Nelson WA;Wargo AR;Sim DG;Drew DR;Read AF
耐药疟疾寄生虫在种群中传播速度的一个主要决定因素是共享同一宿主的耐药和敏感寄生虫的生态。药物治疗可以通过去除对药物敏感的寄生虫来显著改变这种生态，从而导致耐药寄生虫的竞争性释放。在这里，我们检验了一个假设，即通过减少药物治疗，从而限制竞争性释放，可以减缓耐药性的传播。使用啮齿动物疟疾模型，我们发现低剂量化疗确实减少了竞争性释放。较高的药物剂量方案对耐药寄生虫产生更强的阳性选择，但没有检测到临床获益。我们估计了整个重复感染过程中的瞬时选择系数，以分析宿主内选择的强度和方向的时间模式。耐药性选择的强度在感染过程中有所不同，即使在未经治疗的感染中也是如此，但在药物治疗后立即增加，特别是在高剂量组中。耐药性在正选择下保持的时间比药物半衰期预期的要长得多。尽管小鼠和人之间存在许多差异，但我们的数据确实提出了一个问题，即旨在完全清除寄生虫的积极治疗方案是否是人类最佳的耐药性管理策略。
A major determinant of the rate at which drug-resistant malaria parasites spread through a population is the ecology of resistant and sensitive parasites sharing the same host. Drug treatment can significantly alter this ecology by removing the drug-sensitive parasites, leading to competitive release of resistant parasites. Here, we test the hypothesis that the spread of resistance can be slowed by reducing drug treatment and hence restricting competitive release. Using the rodent malaria model Plasmodium chabaudi, we found that low-dose chemotherapy did reduce competitive release. A higher drug dose regimen exerted stronger positive selection on resistant parasites for no detectable clinical gain. We estimated instantaneous selection coefficients throughout the course of replicate infections to analyze the temporal pattern of the strength and direction of within-host selection. The strength of selection on resistance varied through the course of infections, even in untreated infections, but increased immediately following drug treatment, particularly in the high-dose groups. Resistance remained under positive selection for much longer than expected from the half life of the drug. Although there are many differences between mice and people, our data do raise the question whether the aggressive treatment regimens aimed at complete parasite clearance are the best resistance-management strategies for humans.
登录
查看更多内容
影响因子：
6.4
作者：
Cortese, JF;Caraballo, A;Plowe, CV
通讯作者：
Plowe, CV
DOI：
10.1073/pnas.0500078102
发表时间：
2005-05-24
影响因子：
11.1
作者：
de Roode, JC;Pansini, R;Read, AF
通讯作者：
Read, AF
DOI：
10.1073/pnas.0901415106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Harrington, W. E.;Mutabingwa, T. K.;Duffy, P. E.
通讯作者：
Duffy, P. E.
影响因子：
2
作者：
A-Elbasit, Ishraga E.;ElGhazali, Gehad;Giha, Hayder A.
通讯作者：
Giha, Hayder A.
影响因子：
2.4
作者：
Buckling, A;Ranford-Cartwright, LC;Read, AF
通讯作者：
Read, AF