Paul Richard E, Bonnet Sarah, Boudin Christian, Tchuinkam Timoleon, Robert Vincent
Laboratoire d'Entomologie Médicale, Institut Pasteur de Dakar, 36 Avenue Pasteur, BP 220 Dakar, Sénégal.
Malar J. 2007 Sep 12;6:123. doi: 10.1186/1475-2875-6-123.
Despite a long history of attempts to model malaria epidemiology, the over-riding conclusion is that a detailed understanding of host-parasite interactions leading to immunity is required. It is still not known what governs the duration of an infection and how within-human parasite dynamics relate to malaria epidemiology.
Immunity to Plasmodium falciparum develops slowly and requires repeated exposure to the parasite, which thus generates age-structure in the host-parasite interaction. An age-structured degree of immunity would present the parasite with humans of highly variable quality. Evolutionary theory suggests that natural selection will mould adaptive phenotypes that are more precise (less variant) in "high quality" habitats, where lifetime reproductive success is best. Variability in malaria parasite gametocyte density is predicted to be less variable in those age groups who best infect mosquitoes. Thus, the extent to which variation in gametocyte density is a simple parasite phenotype reflecting the complex within-host parasite dynamics is addressed.
Gametocyte densities and corresponding infectiousness to mosquitoes from published data sets and studies in both rural and urban Cameroon are analysed. The mean and variation in gametocyte density according to age group are considered and compared with transmission success (proportion of mosquitoes infected). Across a wide range of settings endemic for malaria, the age group that infected most mosquitoes had the least variation in gametocyte density, i.e. there was a significant relationship between the variance rather than the mean gametocyte density and age-specific parasite transmission success. In these settings, the acquisition of immunity over time was evident as a decrease in asexual parasite densities with age. By contrast, in an urban setting, there were no such age-structured relationships either with variation in gametocyte density or asexual parasite density.
Gametocyte production is seemingly predicted by evolutionary theory, insofar as a reproductive phenotype (gametocyte density) is most precisely expressed (i.e. is most invariant) in the most infectious human age group. This human age group would thus be expected to be the habitat most suitable for the parasite. Comprehension of the immuno-epidemiology of malaria, a requisite for any vaccine strategies, remains poor. Immunological characterization of the human population stratified by parasite gametocyte allocation would be a step forward in identifying the salient immunological pathways of what makes a human a good habitat.
尽管长期以来人们一直试图建立疟疾流行病学模型，但一个压倒性的结论是，需要详细了解导致免疫的宿主 - 寄生虫相互作用。目前仍不清楚是什么决定了感染的持续时间，以及人体内寄生虫动态与疟疾流行病学之间的关系。
对恶性疟原虫的免疫力发展缓慢，需要反复接触该寄生虫，因此在宿主 - 寄生虫相互作用中产生了年龄结构。具有年龄结构的免疫程度会使寄生虫面对质量高度可变的人类宿主。进化理论表明，自然选择将塑造在“高质量”栖息地中更精确（变异较小）的适应性表型，在这些栖息地中，终身繁殖成功率最高。预计在最易感染蚊子的年龄组中，疟原虫配子体密度的变异性较小。因此，本文探讨了配子体密度的变化在多大程度上是一种反映复杂的宿主体内寄生虫动态的简单寄生虫表型。
分析了喀麦隆农村和城市已发表数据集及研究中的配子体密度以及相应的对蚊子的感染性。考虑并比较了不同年龄组配子体密度的均值和变异性，并与传播成功率（感染蚊子的比例）进行对比。在广泛的疟疾流行地区，感染蚊子最多的年龄组配子体密度的变异性最小，即配子体密度的方差而非均值与特定年龄的寄生虫传播成功率之间存在显著关系。在这些地区，随着时间推移免疫力的获得表现为无性寄生虫密度随年龄增长而降低。相比之下，在城市环境中，无论是配子体密度还是无性寄生虫密度的变化，都不存在这种年龄结构关系。
就繁殖表型（配子体密度）在最具感染性的人类年龄组中最精确地表达（即最稳定）而言，配子体产生似乎可以用进化理论来预测。因此，这个人类年龄组预计将是最适合该寄生虫的栖息地。对疟疾免疫流行病学的理解仍然不足，而这是任何疫苗策略的必要条件。按寄生虫配子体分配对人群进行免疫特征分析将是朝着确定使人类成为良好栖息地的关键免疫途径迈出的一步。
