Togetherness amongPlasmodium falciparumgametocytes: interpretation through simulation and consequences for malaria transmission

Abstract

Previous experimental gametocyte infections of Anopheles arabiensis on 3 volunteers naturally infected with Plasmodium falciparum were conducted in Senegal. They showed that gametocyte counts in the mosquitoes are, like macroparasite intakes, heterogeneous (overdispersed). They followed a negative binomial distribution, the overdispersion coefficient seeming constant (k = 3.1). To try to explain this heterogeneity, we used an individual-based model (IBM), simulating the behaviour of gametocytes in the human blood circulation and their ingestion by mosquitoes. The hypothesis was that there exists a clustering of the gametocytes in the capillaries. From a series of simulations, in the case of clustering the following results were obtained: (i) the distribution of the gametocytes ingested by the mosquitoes followed a negative binomial, (ii) the k coefficient significantly increased with the density of circulating gametocytes. To validate this model result, 2 more experiments were conducted in Cameroon. Pooled experiments showed a distinct density dependency of the k-values. The simulation results and the experimental results were thus in agreement and suggested that an aggregation process at the microscopic level might produce the density-dependent overdispersion at the macroscopic level. Simulations also suggested that the clustering of gametocytes might facilitate fertilization of gametes.

Attraction between sexes: male–female gametocyte behaviour within a Leucocytozoon toddi (Haemosporida)

“…However, this observation did not fulfil the speculative prediction of possible sexual preference in such clustering. Moreover, counter to predictions by Gaillard et al (2003), in this instance, the aggregation of gametocytes occurred in conjunction with high gametocytaemia rather than as an adaptation to low gametocytaemia.…”

“…The binding behaviour observed here fulfils predictions by Gautret et al (1996a, b), Gaillard et al (2003) and Pichon et al (2000) that aggregation of gametocytes is possible. However, this observation did not fulfil the speculative prediction of possible sexual preference in such clustering.…”

“…Subsequently, it has been hypothesised that not only may there be a clustering of gametocytes within the vertebrate host capillaries but that clustered gametocytes may also potentially be able to bind with one another, possibly even preferentially with those of the opposite sex (Gaillard et al 2003;Pichon et al 2000). However, these authors also recognised that no convincing microscopic evidence had yet been found for such behaviour.…”

Double gametocyte infections in apicomplexan parasites of birds and reptiles

“…The hypothesis proposed by Gaillard et al (2003) agrees with the discovered pattern of aggregated distribution of erythrocytes infected by malaria gametocytes, both in human blood (Gaillard et al 2003) and in the vector bloodmeal (Pichon et al 2000). The ''DGI hypothesis'' relies on the assumption that DGIs, and especially male-female DGIs, are widespread in nature, but this is currently unconfirmed (Jovani 2002).…”

“…one blood cell infected by one male and one female gametocyte) might reduce the time needed for male gametes to encounter female gametes, facilitating parasite transmission between vertebrate hosts. Gaillard et al (2003) recently proposed that erythrocytes infected by gametocytes could adhere among them in peripheral host capillaries, enhancing the probability of gamete encounter once in the vector bloodmeal.…”