Clinically immune hosts as a refuge for drug-sensitive malaria parasites.
Clinically immune hosts as a refuge for drug-sensitive malaria parasites.
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临床免疫宿主是对药物敏感疟疾寄生虫的避难所。
DOI：
10.1186/1475-2875-7-67
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发表时间：
2008-04-25
期刊：
影响因子：
3
通讯作者：
Laxminarayan R
中科院分区：
文献类型：
--
作者：
Klein EY;Smith DL;Boni MF;Laxminarayan R
在恶性疟原虫中赋予一线抗疟药的突变已经从几个独立的灶中传播到世界各地，它们都位于可能以低或不稳定的疟疾传播为特征的地区。低或不稳定的疟疾传播和高流行区域之间的显着差异是免疫个体人群大小的差异。但是，假设它们不影响寄生虫的适应性，那么疟疾传播的流行病学模型通常忽略了免疫个体在传播中的作用。该模型在免疫个体具有传染性的假设下，重新塑造了免疫力在疟疾传播动力学及其对抗疟疾耐药性进化的影响。
该模型被构建为疟疾传播的两阶段易感感染感受的（SIS）模型，该模型假设个体在几年内建立临床免疫力。这种免疫力降低了临床症状的频率和严重程度，从而减少了药物的使用。它还降低了个人的传染性水平，但不会影响被感染的可能性。
模拟发现，随着抗药性引入人群，临床免疫力可以显着改变耐药性寄生虫的适应性，从而影响耐药性寄生虫通过减少有效的抗性寄生虫数量作为最初宿主传播的能力，因为抗性寄生虫数量是有效的抗性寄生虫数量传输强度增加。在高传输水平上，尽管基本的生殖数量较高，R0的有效生殖数可能低于敏感寄生虫的生殖数。
这些结果表明，高水平的临床免疫力为药物敏感的寄生虫创造了自然的生态避难所。这为抵抗出现的历史模式提供了一个流行病学的理由，并表明，在低或不稳定的传递环境中，未来的抵抗爆发更有可能发生。这一发现对药物政策的设计和疟疾控制策略的制定具有影响，尤其是那些降低疟疾传播强度的策略。
Mutations in Plasmodium falciparum that confer resistance to first-line antimalarial drugs have spread throughout the world from a few independent foci, all located in areas that were likely characterized by low or unstable malaria transmission. One of the striking differences between areas of low or unstable malaria transmission and hyperendemic areas is the difference in the size of the population of immune individuals. However, epidemiological models of malaria transmission have generally ignored the role of immune individuals in transmission, assuming that they do not affect the fitness of the parasite. This model reconsiders the role of immunity in the dynamics of malaria transmission and its impact on the evolution of antimalarial drug resistance under the assumption that immune individuals are infectious. The model is constructed as a two-stage susceptible-infected-susceptible (SIS) model of malaria transmission that assumes that individuals build up clinical immunity over a period of years. This immunity reduces the frequency and severity of clinical symptoms, and thus their use of drugs. It also reduces an individual's level of infectiousness, but does not impact the likelihood of becoming infected. Simulations found that with the introduction of resistance into a population, clinical immunity can significantly alter the fitness of the resistant parasite, and thereby impact the ability of the resistant parasite to spread from an initial host by reducing the effective reproductive number of the resistant parasite as transmission intensity increases. At high transmission levels, despite a higher basic reproductive number, R0, the effective reproductive number of the resistant parasite may fall below the reproductive number of the sensitive parasite. These results suggest that high-levels of clinical immunity create a natural ecological refuge for drug-sensitive parasites. This provides an epidemiological rationale for historical patterns of resistance emergence and suggests that future outbreaks of resistance are more likely to occur in low- or unstable-transmission settings. This finding has implications for the design of drug policies and the formulation of malaria control strategies, especially those that lower malaria transmission intensity.
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影响因子：
6.4
作者：
Cortese, JF;Caraballo, A;Plowe, CV
通讯作者：
Plowe, CV
DOI：
10.4269/ajtmh.1991.45.65
发表时间：
1991-07-01
影响因子：
3.3
作者：
BAIRD, JK;JONES, TR;MASBAR, S
通讯作者：
MASBAR, S
影响因子：
--
作者：
Baird, JK;Krisin;Kalalo, W
通讯作者：
Kalalo, W
DOI：
10.4269/ajtmh.2003.69.558
发表时间：
2003-11-01
影响因子：
3.3
作者：
Djimdé, AA;Doumbo, OK;Plowe, CV
通讯作者：
Plowe, CV
影响因子：
4.3
作者：
ARON, JL
通讯作者：
ARON, JL