The population dynamics of Plasmodium within the mosquito

Abstract

Malaria remains one of the world’s most devastating vector-borne parasitic diseases and existing control tools may not be enough to meet the challenge of eliminating malaria in areas of high transmission. Understanding the population dynamics of Plasmodium within the mosquito vector is essential for developing, optimising, and evaluating novel control measures aimed at reducing transmission by targeting this important interface. Malaria research and mathematical models of transmission classically assume that the processes involved in the progression and development of the Plasmodium parasite within Anopheles mosquitoes are independent of parasite density. The research presented in this thesis challenges this assumption, investigating the impact of parasite density on population processes and regulation. A multidisciplinary approach has been taken, including statistical analyses, practical experimentation, and mathematical modelling. The results show that the progression of the rodent malaria Plasmodium berghei through Anopheles stephensi mosquitoes depends nonlinearly on parasite density, with the presence of both negative and positive density-dependent processes in operation. Analyses of other Plasmodium– Anopheles species combinations also indicate that the traditional assumption of density independence may be an oversimplification. Experimental investigation of mosquito mortality illustrates that the survival of a mosquito depends both on mosquito age and parasite density, again in contrast to the assumptions of malaria transmission modelling. A framework for a mathematical model tracking Plasmodium density within the mosquito has been developed as part of this thesis. Further investigation of sporogonic processes will allow this model to be further refined and extended for use in the future design and evaluation of interventions which target the mosquito or the parasite whilst within the vector.