Malaria host manipulation increases probability of mosquitoes feeding on humans

Alison Duncan based on reviews by Ricardo S. Ramiro, Olivier Restif and 1 anonymous reviewer

A recommendation of:
Amelie Vantaux, Franck Yao, Domonbabele FdS Hien, Edwige Guissou, Bienvenue K Yameogo, Louis-Clement Gouagna, Didier Fontenille, Francois Renaud, Frederic Simard, Carlo Constantini, Frederic Thomas, Karine Mouline, Benjamin Roche, Anna Cohuet, Kounbobr R Dabire, Thierry Lefevre. Field evidence for manipulation of mosquito host selection by the human malaria parasite, Plasmodium falciparum bioRxiv, 2018, 207183, ver. 6 peer-reviewed and recommended by Peer Community in Evolutionary Biology. 10.1101/207183
Submitted: 28 February 2018, Recommended: 31 October 2018
Cite this recommendation as:
Alison Duncan (2018) Malaria host manipulation increases probability of mosquitoes feeding on humans. Peer Community in Evolutionary Biology, 100057. 10.24072/pci.evolbiol.100057

Parasites can manipulate their host’s behaviour to ensure their own transmission. These manipulated behaviours may be outside the range of ordinary host activities [1], or alter the crucial timing and/or location of a host’s regular activity. Vantaux et al show that the latter is true for the human malaria parasite, Plasmodium falciparum [2]. They demonstrate that three species of Anopheles mosquito were 24% more likely to choose human hosts, rather than other vertebrates, for their blood feed when they harboured transmissible stages (sporozoites) compared to when they were uninfected, or infected with non-transmissible malaria parasites [2]. Host choice is crucial for the malaria parasite Plasmodium falciparum to complete its life-cycle, as their host range is much narrower than the mosquito’s for feeding; P. falciparum can only develop in hominids, or closely related apes [3].
The study only shows this stage-dependent parasite manipulation retrospectively (by identifying host type and parasite stage in mosquitoes after their blood feed [2]). There was no difference in the preferences of infectious (with sporozoites) or un-infectious (infected without sporozoites, or uninfected) mosquitoes between human versus cow hosts in a choice test [2]. This suggests that the final decision about whether to feed occurs when the mosquito is in close range of the host.
This, coupled with previous findings, shows that vector manipulation is a fine-tuned business, that can act at multiple stages of the parasite life-cycle and on many behaviours [4]. Indeed, mosquitoes with non-transmissible Plasmodium stages (oocysts) are more reluctant to feed than sporozoite-infected mosquitoes [5] as vectors can be killed by their host whilst feeding, doing so before they are ready to transmit is risky for the malaria parasite. Thus, it seems that Plasmodium is, to some extent, master of its vector; commanding it not to feed when it cannot be transmitted, to feed when it is ready to be transmitted and to feed on the right type of host. What does this mean for our understanding of malaria transmission and epidemics?
Vantaux et al use a mathematical model, parameterised using data from this experiment, to highlight the consequences of this 24% increase in feeding on humans for P. falciparum transmission. They show that this increase raises the number of infectious bites humans receive from 4 (if sporozoite-infected mosquitoes had the same probability as uninfected mosquitoes) to 14 (an increase in 250%), for mosquitoes with a 15-day life-span, at ratios of 1:1 mosquitoes to humans. Longer mosquito life-spans and higher ratios of mosquitoes to humans further increases the number of infectious bites.
These results [2] have important implications for epidemiological forecasting and disease management. Public health strategies could focus on possible ways to trap sporozoite-infected mosquitoes, mimicking cues they use to locate their human hosts, or identify the behaviour of mosquitoes harbouring non-yet infectious Plasmodium, and trap them before they bite. Moreover, the results of the model show that failing to take into account the preference for humans of sporozoite-infected mosquitoes could underestimate the size of pending epidemics.
An important question previously raised is whether Plasmodium-induced alteration in host behaviour really is manipulation, or just a side-effect of being infected [4,5]. The fact that Vantaux et al show that these altered feeding behaviours increases the likelihood of transmission, in that a sporozoite-infected mosquito is more likely to feed on a human, strongly suggests that it is adaptive for the parasite [2]. Ultimately, to show that it is manipulation would require the identification of molecular factors released by Plasmodium that are responsible for physiological changes in the mosquito [6].

References

[1] Thomas, F., Schmidt-Rhaesa, A., Martin, G., Manu, C., Durand, P., & Renaud, F. (2002). Do hairworms (Nematomorpha) manipulate the water seeking behaviour of their terrestrial hosts? Journal of Evolutionary Biology, 15(3), 356–361. doi: 10.1046/j.1420-9101.2002.00410.x
[2] Vantaux, A., Yao, F., Hien, D. F., Guissou, E., Yameogo, B. K., Gouagna, L.-C., … Lefevre, T. (2018). Field evidence for manipulation of mosquito host selection by the human malaria parasite, Plasmodium falciparum. BioRxiv, 207183 ver 6. doi: 10.1101/207183
[3] Prugnolle, F., Durand, P., Ollomo, B., Duval, L., Ariey, F., Arnathau, C., … Renaud, F. (2011). A Fresh Look at the Origin of Plasmodium falciparum, the Most Malignant Malaria Agent. PLOS Pathogens, 7(2), e1001283. doi: 10.1371/journal.ppat.1001283
[4] Cator, L. J., Lynch, P. A., Read, A. F., & Thomas, M. B. (2012). Do malaria parasites manipulate mosquitoes? Trends in Parasitology, 28(11), 466–470. doi: 10.1016/j.pt.2012.08.004
[5] Cator, L. J., George, J., Blanford, S., Murdock, C. C., Baker, T. C., Read, A. F., & Thomas, M. B. (2013). “Manipulation” without the parasite: altered feeding behaviour of mosquitoes is not dependent on infection with malaria parasites. Proceedings. Biological Sciences, 280(1763), 20130711. doi: 10.1098/rspb.2013.0711
[6] Herbison, R., Lagrue, C., & Poulin, R. (2018). The missing link in parasite manipulation of host behaviour. Parasites & Vectors, 11. doi: 10.1186/s13071-018-2805-9