Lawniczak Mara K N, Eckhoff Philip A
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Institute for Disease Modeling, 3150 139th Avenue SE, Bellevue, WA, 98005, USA.
Malar J. 2016 Sep 21;15(1):487. doi: 10.1186/s12936-016-1538-5.
The burden of falciparum malaria remains unacceptably high in much of sub-Saharan Africa and massive efforts are underway to eliminate the parasite. While symptoms of malaria are caused by asexual reproduction of the parasite, transmission to new human hosts relies entirely on male and female sexual-stage parasites, known as gametocytes. Successful transmission can be observed at very low gametocyte densities, which raises the question of whether transmission-enhancing mechanisms exist in the human host, the mosquito, or both.
A new computational model was developed to investigate the probability of fertilization over a range of overdispersion parameters and male gamete exploration rates. Simulations were used to fit a likelihood surface for data on rates of mosquito infection across a wide range of host gametocyte densities.
The best fit simultaneously requires very strong overdispersion and faster gamete exploration than is possible with random swimming in order to explain typical prevalence levels in mosquitoes. Gametocyte overdispersion or clustering in the human host and faster gamete exploration of the mosquito blood meal are highly probably given these results.
Density-dependent gametocyte clustering in the human host, and non-random searching (e.g., chemotaxis) in the mosquito are probable. Future work should aim to discover these mechanisms, as disrupting parasite development in the mosquito will play a critical role in eliminating malaria.
在撒哈拉以南非洲的大部分地区，恶性疟原虫的负担仍然高得令人无法接受，目前正在开展大规模努力来消灭这种寄生虫。虽然疟疾症状是由寄生虫的无性繁殖引起的，但向新的人类宿主传播则完全依赖于称为配子体的雄性和雌性有性阶段寄生虫。在非常低的配子体密度下就能观察到成功传播，这就引发了一个问题，即人类宿主、蚊子或两者中是否存在增强传播的机制。
开发了一种新的计算模型，以研究在一系列过度分散参数和雄配子探索率范围内的受精概率。利用模拟来拟合一个似然面，该似然面用于表示在广泛的宿主配子体密度范围内蚊子感染率的数据。
为了解释蚊子中的典型流行水平，最佳拟合同时需要非常强的过度分散和比随机游动更快的配子探索。鉴于这些结果，很可能在人类宿主中存在配子体过度分散或聚集现象，并且蚊子吸食的血液中配子探索更快。
人类宿主中可能存在密度依赖性配子体聚集，以及蚊子中的非随机搜索（例如趋化性）。未来的工作应旨在发现这些机制，因为破坏蚊子体内的寄生虫发育将在消除疟疾中发挥关键作用。
