  Malaria is a major contributor to health burdens throughout the regions where
it is endemic. Historically, it was believed that there was limited morbidity
and essentially no mortality associated with Plasmodium vivax; however,
evidence from diverse settings now suggests that infections with P. vivax can
be both severe and fatal. This awareness has highlighted a critical gap: the
vast majority of research has been directed towards P. falciparum, leading to a
decades-long neglect of epidemiological and clinical studies of P. vivax. There
exists a large body of historical data on human experimental infections with P.
vivax; these studies in controlled settings provided a wealth of wide-ranging
statements based on expert opinion, which form the basis for much of what is
currently known about P. vivax. In this thesis, portions of this evidence-base
have been re-examined using modern epidemiological analyses with two aims: to
critically examine this accumulated knowledge base, and to inform current
research agendas towards global malaria elimination for all species of
Plasmodium. Chapter 2 examines geographic variation in the epidemiology of P.
vivax, especially the timing of incubation periods and of relapses, by origin
of the parasites. Chapter 3 re-assesses the impact of sporozoite dosage upon
incubation and pre-patent periods; Chapter 4 provides well-defined mathematical
distributions for incubation and relapses periods in experimental infections,
and explores their epidemiological impacts using simple transmission models.
Chapter 5 examines the epidemiology of mixed-strain P. vivax infections and
compares these results with studies in murine models and general ecological
theory; and Chapter 6 clarifies the origin of the Madagascar strain of P.
vivax.
