Simulating within-vector generation of the malaria parasite diversity
Simulating within-vector generation of the malaria parasite diversity
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DOI：
10.1371/journal.pone.0177941
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发表时间：
2017-05-22
期刊：
影响因子：
3.7
通讯作者：
Prosper, Olivia F.
中科院分区：
文献类型：
--
作者：
Childs, Lauren M.;Prosper, Olivia F.
恶性疟原虫是最致命的人类疟疾寄生虫，在人类宿主体内进行无性繁殖，但在其媒介宿主按蚊体内进行有性繁殖。因此，寄生虫生命周期的蚊子阶段提供了在多重感染的蚊子中创造遗传新寄生虫的机会，潜在地增加了寄生虫种群的多样性。尽管这对疾病传播和疟疾控制具有重要意义，但尚未对进入蚊子的寄生虫多样性与离开蚊子的寄生虫多样性之间的关系进行定量绘图。为了研究媒介生物学在调节寄生虫多样性中所起的作用，我们开发了一个由两部分组成的模型框架，该框架估计了寄生虫生命周期中媒介阶段发生的不同瓶颈和扩展事件所导致的多样性。对于潜在的框架，我们开发了第一个载体内恶性疟原虫动态的随机模型，并继续模拟两个寄生虫亚种群的动态，模拟多重感染的蚊子。我们表明，纳入随机性是必不可少的，以捕捉寄生虫动力学的广泛变化，特别是在多种寄生虫的存在。特别是，不像确定性模型总是预测最适合的寄生虫产生最多的孢子子，我们发现偶尔只有适应性较低的寄生虫才能存活到孢子子阶段。这对后续传播具有重要意义。我们框架的第二部分包括一个序列多样性产生的模型，该模型是由蚊子体内寄生虫之间的重组和重组引起的。我们的两部分模型框架表明，进入卵囊阶段的瓶颈减少了蚊子血液中初始配子体种群中存在的寄生虫多样性。然而，多样性随着孢子形成过程中重组和增殖的可能性而增加。此外，当我们从初始配子细胞群中的两个寄生虫亚群开始时，在很大的初始配子细胞密度范围内，从蚊子向人类传播两种以上独特寄生虫的概率超过50%。
Plasmodium falciparum, the most virulent human malaria parasite, undergoes asexual reproduction within the human host, but reproduces sexually within its vector host, the Anopheles mosquito. Consequently, the mosquito stage of the parasite life cycle provides an opportunity to create genetically novel parasites in multiply-infected mosquitoes, potentially increasing parasite population diversity. Despite the important implications for disease transmission and malaria control, a quantitative mapping of how parasite diversity entering a mosquito relates to diversity of the parasite exiting, has not been undertaken. To examine the role that vector biology plays in modulating parasite diversity, we develop a two-part model framework that estimates the diversity as a consequence of different bottlenecks and expansion events occurring during the vector-stage of the parasite life cycle. For the underlying framework, we develop the first stochastic model of within-vector P. falciparum parasite dynamics and go on to simulate the dynamics of two parasite subpopulations, emulating multiply infected mosquitoes. We show that incorporating stochasticity is essential to capture the extensive variation in parasite dynamics, particularly in the presence of multiple parasites. In particular, unlike deterministic models, which always predict the most fit parasites to produce the most sporozoites, we find that occasionally only parasites with lower fitness survive to the sporozoite stage. This has important implications for onward transmission. The second part of our framework includes a model of sequence diversity generation resulting from recombination and reassortment between parasites within a mosquito. Our two-part model framework shows that bottlenecks entering the oocyst stage decrease parasite diversity from what is present in the initial gametocyte population in a mosquito's blood meal. However, diversity increases with the possibility for recombination and proliferation in the formation of sporozoites. Furthermore, when we begin with two parasite subpopulations in the initial gametocyte population, the probability of transmitting more than two unique parasites from mosquito to human is over 50% for a wide range of initial gametocyte densities.