Epidemiology of Latency and Relapse in Plasmodium vivax Malaria

TL;DR

This paper critically re-examines historical and experimental data on P. vivax malaria using modern epidemiological methods to better understand its incubation, relapse patterns, and geographic variation, informing global elimination strategies.

Contribution

It provides new epidemiological analyses of P. vivax, including incubation and relapse distributions, geographic variation, and mixed infections, filling gaps left by previous research focus on P. falciparum.

Findings

Geographic variation affects incubation and relapse timing.

Sporozoite dosage influences incubation periods.

Mathematical distributions model incubation and relapse periods.

Abstract

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.