Last-come, best served? Mosquito biting order and Plasmodium transmission

Abstract

A pervasive characteristic of malaria parasite infection in mosquito vector populations is their tendency to be overdispersed. Understanding the mechanisms underlying the overdispersed distribution of parasites is of key importance as it may drastically impact the transmission dynamics of the pathogen. The small fraction of heavily infected individuals might serve as superspreaders and cause a disproportionate number of subsequent infections. Although multiple factors ranging from environmental stochasticity to inter-individual heterogeneity may explain parasite overdispersion, Plasmodium infection has also been observed to be highly overdispersed in inbred mosquito population maintained under standardized laboratory conditions, suggesting that other mechanisms may be at play. Here, we show that the aggregated distribution of Plasmodium within mosquito vectors is partially explained by a temporal heterogeneity in parasite infectivity triggered by the bites of blood-feeding mosquitoes. Several experimental blocks carried out with three different Plasmodium isolates have consistently shown that the transmission of the parasite increases progressively with the order of mosquito bites. Surprisingly the increase in transmission is not associated with an increase in Plasmodium replication rate or higher investment in the production of the transmissible stage (gametocyte). Adjustment of the physiological state of the gametocytes could be, however, an adaptive strategy to respond promptly to mosquito bites. Overall our data show that malaria parasite appears to be able to respond to the bites of mosquitoes to increase its own transmission at a much faster pace than initially thought (hours rather than days). Further work needs to be carried out to elucidate whether these two strategies are complementary and, particularly, what are their respective underlaying mechanisms. Understanding the processes underlying the temporal fluctuations in Plasmodium infectivity throughout vertebrate host-to-mosquito transmission is essential and could lead to the development of new approaches to control malaria transmission. Author summaryPlasmodium parasites are known for being the etiological agents of malaria and for the devastating effects they cause on human populations. A pervasive characteristic of Plasmodium infection is their tendency to be overdispersed in mosquito vector populations: the majority of mosquitoes tend to harbour few or no parasites while a few individuals harbor the vast majority of the parasite population. Understanding the mechanisms underlying Plasmodium overdispersed distribution is of key importance as it may drastically impact the transmission dynamics of the pathogen. Here, we show that the aggregated distribution of Plasmodium parasites within mosquito vectors is partially explained by a temporal heterogeneity in Plasmodium infectivity triggered by the bites of blood-feeding mosquitoes. In other words, mosquitoes that bite at the beginning of a 3h feeding session have significantly fewer parasites than those that bite towards the end. Malaria parasite is therefore capable of responding to the bites of mosquitoes to increase its own transmission at a much faster pace than thought (hours rather than days). Understanding the processes underlying the temporal fluctuations in Plasmodium infectivity throughout vertebrate host-to-mosquito transmission is essential and could lead to the development of new approaches to control malaria transmission.