Medicine: Department of Infectious Disease Epidemiology, Imperial College London
Doi
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
