Geographical variation in Plasmodium vivax relapse.

Katherine E Battle,Rosalind E Howes,J Kevin Baird,Samir Bhatt,Peter W Gething,Simon I Hay,Markku S Karhunen,Thomas P Van Boeckel,Jane P Messina,G Dennis Shanks,Nick Golding,David L Smith

doi:10.1186/1475-2875-13-144

Abstract

BackgroundPlasmodium vivax has the widest geographic distribution of the human malaria parasites and nearly 2.5 billion people live at risk of infection. The control of P. vivax in individuals and populations is complicated by its ability to relapse weeks to months after initial infection. Strains of P. vivax from different geographical areas are thought to exhibit varied relapse timings. In tropical regions strains relapse quickly (three to six weeks), whereas those in temperate regions do so more slowly (six to twelve months), but no comprehensive assessment of evidence has been conducted. Here observed patterns of relapse periodicity are used to generate predictions of relapse incidence within geographic regions representative of varying parasite transmission.MethodsA global review of reports of P. vivax relapse in patients not treated with a radical cure was conducted. Records of time to first P. vivax relapse were positioned by geographic origin relative to expert opinion regions of relapse behaviour and epidemiological zones. Mixed-effects meta-analysis was conducted to determine which geographic classification best described the data, such that a description of the pattern of relapse periodicity within each region could be described. Model outputs of incidence and mean time to relapse were mapped to illustrate the global variation in relapse.ResultsDifferences in relapse periodicity were best described by a historical geographic classification system used to describe malaria transmission zones based on areas sharing zoological and ecological features. Maps of incidence and time to relapse showed high relapse frequency to be predominant in tropical regions and prolonged relapse in temperate areas.ConclusionsThe results indicate that relapse periodicity varies systematically by geographic region and are categorized by nine global regions characterized by similar malaria transmission dynamics. This indicates that relapse may be an adaptation evolved to exploit seasonal changes in vector survival and therefore optimize transmission. Geographic patterns in P. vivax relapse are important to clinicians treating individual infections, epidemiologists trying to infer P. vivax burden, and public health officials trying to control and eliminate the disease in human populations.

Highlights

Plasmodium vivax has the widest geographic distribution of the human malaria parasites and nearly 2.5 billion people live at risk of infection
Plasmodium vivax gametocytes are present earlier in the progression of a primary or recrudescent infection compared to P. falciparum [17,22], such that the majority of patients have sufficient gametocytaemia to allow for transmission before diagnosis or treatment may occur [23,24,25]
The literature sources ostensibly refer to the recurrence events as relapses; treatment trials and studies conducted in endemic areas may include recrudescences and reinfections in measures of relapse

Summary

Introduction

Plasmodium vivax has the widest geographic distribution of the human malaria parasites and nearly 2.5 billion people live at risk of infection. The control of P. vivax in individuals and populations is complicated by its ability to relapse weeks to months after initial infection. Plasmodium vivax is epidemiologically and biologically different to P. falciparum and it is not, appropriate to assume that control methods developed for falciparum malaria are directly transferable to P. vivax [13,14,15,16]. Plasmodium vivax gametocytes are present earlier in the progression of a primary or recrudescent infection compared to P. falciparum [17,22], such that the majority of patients have sufficient gametocytaemia to allow for transmission before diagnosis or treatment may occur [23,24,25]. P. vivax sporozoites develop faster than P. falciparum at equivalent temperatures, which contributes to its exploitation of a wider geographic range [28]

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