Abstract

BackgroundTanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been achieved. Importation of parasites from outside of the archipelago is thought to be an important cause of malaria’s persistence, but this paradigm has not been studied using modern genetic tools.MethodsWhole-genome sequencing (WGS) was used to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania. Ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations were assessed by leveraging recent advances in deconvolution of genomes from polyclonal malaria infections.ResultsSignificant decreases in the effective population sizes were inferred in both populations that coincide with a period of decreasing malaria transmission in Tanzania. Identity by descent analysis showed that parasites in the two populations shared long segments of their genomes, on the order of 5 cM, suggesting shared ancestry within the last 10 generations. Even with limited sampling, two of isolates between the mainland and Zanzibar were identified that are related at the expected level of half-siblings, consistent with recent importation.ConclusionsThese findings suggest that importation plays an important role for malaria incidence on Zanzibar and demonstrate the value of genomic approaches for identifying corridors of parasite movement to the island.

Highlights

  • Tanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination

  • Identity by descent (IBD), the sharing of discrete genomic segments inherited from a common genealogical ancestor, has been found to be a good metric for studying the interconnectivity of parasite populations [11,12,13]

  • These came from crosssectional surveys of asymptomatic individuals (n = 34) and an in vivo efficacy study of artesunate–amodiaquine (ASAQ) with single low dose primaquine (SLDP) in paediatric uncomplicated malaria patients (n = 29)

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Summary

Introduction

Tanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. The reasons for Zanzibar’s failure to achieve elimination are complex and likely driven by several key factors: (1) as transmission decreases, the distribution of cases changes and residual transmission is more focal and mainly outdoors [3]; (2) a significant number of malaria infections are asymptomatic and untreated and remain a source for local transmission [4,5,6,7]; and (3) the archipelago has a high level of connectivity with the mainland, imported malaria through human travel may play an increasing relative role in transmission. In order to address this obstacle, recent algorithms have been developed to deconvolve multiple infections into their respective strains from Illumina sequence data [14, 15] These advances make it tractable to conduct population genetic analysis of malaria in regions of higher transmission, where infections are often polyclonal

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