Population biology of malaria within the mosquito: density-dependent processes and potential implications for transmission-blocking interventions

Background: The combined effects of multiple density-dependent, regulatory processes may have an important impact on the growth and stability of a population. In a malaria model system, it has been shown that the progression of Plasmodium berghei through Anopheles stephensi and the survival of the mosquito both depend non-linearly on parasite density. These processes regulating the development of the malaria parasite within the mosquito may influence the success of transmission-blocking interventions (TBIs) currently under development. Methods: An individual-based stochastic mathematical model is used to investigate the combined impact of these multiple regulatory processes and examine how TBIs, which target different parasite life-stages within the mosquito, may influence overall parasite transmission. Results: The best parasite molecular targets will vary between different epidemiological settings. Interventions that reduce ookinete density beneath a threshold level are likely to have auxiliary benefits, as transmission would be further reduced by density-dependent processes that restrict sporogonic development at low parasite densities. TBIs which reduce parasite density but fail to clear the parasite could cause a modest increase in transmission by increasing the number of infectious bites made by a mosquito during its lifetime whilst failing to sufficiently reduce its infectivity. Interventions with a higher variance in efficacy will therefore tend to cause a greater reduction in overall transmission than a TBI with a more uniform effectiveness. Care should be taken when interpreting these results as parasite intensity values in natural parasite-vector combinations of human malaria are likely to be significantly lower than those in this model system. Conclusions: A greater understanding of the development of the malaria parasite within the mosquito is required to fully evaluate the impact of TBIs. If parasite-induced vector mortality influenced the population dynamics of Plasmodium species infecting humans in malaria endemic regions, it would be important to quantify the variability and duration of TBI efficacy to ensure that community benefits of control measures are not overestimated.