Microsporidians as effective and evolution-resistant agents of malaria control?

尽管我们努力控制疟疾，但疟疾仍然是我们最严重和最致命的疾病之一。我们的控制之所以失败，部分原因在于这种寄生虫的传播强度之高，可能比我们常见的、更容易控制的疾病（如麻疹）高出几个数量级；另一个原因是，疟疾寄生虫及其蚊媒对用于攻击它们的大多数化学药品产生了抗药性，并产生了抗药性。迫切需要新的控制方法。但是，新方法只有在有效（即大幅减少传播）和可持续（即防止进化降低有效性）的情况下才有用。我将评估利用库氏小孢子虫控制疟疾的潜力，重点关注这两个标准。我将通过估计微孢子虫对几个流行病学相关特征的影响来考虑有效性：蚊子的幼虫死亡率、成虫寿命和叮咬率，以及疟原虫在蚊子体内的发育。将考虑感染疟疾和/或未感染疟疾的成年蚊子的特征。即使寄生虫对这些特征的影响只是适度的，对传播的综合影响也可能是巨大的。但有些菌株可能对一种性状有很强的影响，但对其他性状没有；其他菌株可能对其他性状有很强的影响。如果每个菌株只强烈针对一个性状，则无法达到预期的效果。因此，我也将考虑微孢子虫菌株之间的变异。对于潜在的疟疾控制，我可以选择最有效地减少疟疾传播的菌株（最有可能对每个特征都有中等影响的菌株）。我将通过考虑蚊子之间的（遗传）变异来考虑可持续性。有些蚊子在幼虫时期可能对被杀死有抵抗力，有些蚊子可能对其他特征有抵抗力。一个被普遍接受的进化理论认为，如果大量使用微孢子虫使抗性进化，那么最有可能出现的是幼虫的抗性（而不是老年个体的抗性）。此外，抗性通常是代价高昂的，因为它会影响其他性状，例如，增加幼虫抗性可能会降低叮咬率或降低成虫寿命。幸运的是，这些特征在流行病学上比幼虫存活更相关，因此蚊子的进化反应很可能减少传播。耐药性的进化很可能是不可避免的，但控制失败却并非如此。这是否有效主要取决于相关性的细节，这是本研究的重点。这种方法的新颖之处在于，它并不试图阻止进化，而是依赖于流行病学和进化相关特征之间的差异，以积极的流行病学方式利用进化。

Despite our efforts at malaria control, malaria remains one of our most serious and deadly diseases. The failure of our control stems in part from the parasite's intense transmission, which can be several orders of magnitude higher than that of many of our common, more easily controllable diseases such as measles, and from the emergence and spread of resistance of the malaria parasites and their mosquito vectors against most of the chemicals used to attack them. New methods for control are desperately needed. But new methods will be useful only if they are effective (i.e. decrease transmission substantially) and sustainable (i.e. prevent evoluitln from degrading effectivness). I will evaluate the potential of using the microsporidian Vavraia culicis for malaria control, focussing on these two criteria. I will consider effectiveness by estimating the effect of the microsporidian on several epidemiologically relevant traits: the mosquito's larval mortality, adult longevity and biting rate, and the malaria parasite's development in the mosquito. The traits in the adult will be considered for malaria-infected and /uninfected mosquitoes. Even if the parasite affects each of these traits only moderately, the combined effect on transmission can be substantial. But some strains may have a strong effect on one trait, but not on others; other strains may have a strong effect on other traits. If each strain targets only one trait strongly, the desired effecivness will not be reached. Therefore, I will also consider variation among strains of the microsporidian. For potential malaria control, I could select the strain that reduces the transmission of malaria most effectively (most likely one that has a moderate effect on each of the traits). I will consider sustainability by considering (genetic) variation among mosquitoes. Some mosquitoes might be resistant against being killed as larvae, others might be resistant at other traits. A generally accepted evolutionary theory suggests that, if intense use of microsporidians enables resistance to evolve, it will most likely be resistance of larvae (rather than resistance of the older individuals) that emerges. Furthermore resistance is generally costly in the sense that it affects other traits, e.g. increasing larval resistance could decrease biting rate or adult longevity. Luckily, these traits are epidemiologically more relevant than larval survival, so that the mosquito's evolutionary response may well reduce transmission. Evolution of resistance may well be inevitable, but failure of control is not. Whether this works depends critically on the details of the correlations, which is the focus of this study. The novelty of this approach is that it does not try to block evolution, but relies on the difference between epidemiologically and evolutionarily relevant traits to use evolution in an epidemiologically positive way.