Childs Lauren M, Buckee Caroline O
Center for Communicable Disease Dynamics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
Center for Communicable Disease Dynamics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
J R Soc Interface. 2015 Mar 6;12(104):20141379. doi: 10.1098/rsif.2014.1379.
The duration of infection is fundamental to the epidemiological behaviour of any infectious disease, but remains one of the most poorly understood aspects of malaria. In endemic areas, the malaria parasite Plasmodium falciparum can cause both acute, severe infections and asymptomatic, chronic infections through its interaction with the host immune system. Frequent superinfection and massive parasite genetic diversity make it extremely difficult to accurately measure the distribution of infection lengths, complicating the estimation of basic epidemiological parameters and the prediction of the impact of interventions. Mathematical models have qualitatively reproduced parasite dynamics early during infection, but reproducing long-lived chronic infections remains much more challenging. Here, we construct a model of infection dynamics to examine the consequences of common biological assumptions for the generation of chronicity and the impact of co-infection. We find that although a combination of host and parasite heterogeneities are capable of generating chronic infections, they do so only under restricted parameter choices. Furthermore, under biologically plausible assumptions, co-infection of parasite genotypes can alter the course of infection of both the resident and co-infecting strain in complex non-intuitive ways. We outline the most important puzzles for within-host models of malaria arising from our analysis, and their implications for malaria epidemiology and control.
感染持续时间是任何传染病流行病学行为的基础，但仍然是疟疾最不为人所了解的方面之一。在疟疾流行地区，疟原虫恶性疟原虫通过与宿主免疫系统相互作用，可引发急性重症感染和无症状慢性感染。频繁的重复感染以及大量的寄生虫基因多样性使得准确测量感染时长的分布极为困难，这也使得基本流行病学参数的估算以及干预措施影响的预测变得复杂。数学模型已定性地再现了感染初期的寄生虫动态，但再现长期慢性感染仍面临更大挑战。在此，我们构建了一个感染动态模型，以研究常见生物学假设对慢性感染产生的影响以及合并感染的作用。我们发现，虽然宿主和寄生虫的异质性组合能够产生慢性感染，但仅在有限的参数选择下才会如此。此外，在生物学上合理的假设下，寄生虫基因型的合并感染会以复杂且非直观的方式改变常驻菌株和合并感染菌株的感染进程。我们概述了基于我们的分析得出的宿主内疟疾模型最重要的谜团，以及它们对疟疾流行病学和控制的影响。
