Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago

Abstract

Background : Tanzania’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. Methods : We used whole-genome sequencing (WGS) to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania. We assessed ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations by leveraging recent advances in deconvolution of genomes from polyclonal malaria infections. Results : We identified significant decreases in the effective population sizes in both populations in the timeframe of decreasing malaria transmission in Tanzania. Identity by descent analysis showed that parasites in the two populations shared large sections of their genomes, on the order of 5 cM, suggesting shared ancestry within the last 10 generations. Even with limited sampling, we identified a pair of isolates between the mainland and Zanzibar that are related at the expected level of half-siblings, consistent with recent importation Conclusions : These 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.

Strong isolation by distance and evidence of population microstructure reflect ongoingPlasmodium falciparumtransmission in Zanzibar

“…In Zanzibar, highly related parasites mainly occur at the range of 20-30km. These results are similar to our previous work using whole genome sequencing of isolates from Zanzibar and mainland Tanzania, showing increased within population IBD compared to between population IBD (Morgan et al, 2020). The network of highly related P. falciparum parasites from 6 shehias in North Pemba provides an excellent example of likely recent near clonal transmission, consistent with an outbreak ( Figure 4C ).…”

“…Despite these efforts, malaria has been difficult to eliminate from the archipelago. There are several reasons this may be the case: (1) frequent importation of malaria from moderate or high transmission regions of mainland Tanzania and Kenya (Björkman et al, 2019; Le Menach et al, 2011; Lipner et al, 2011; Monroe et al, 2019; Morgan et al, 2020; Tatem et al, 2009); (2) ongoing local transmission due to residual vector capacity despite strong vector control (Björkman et al, 2019); and (3) a reservoir of asymptomatic infections (Björkman & Morris, 2020; Björkman et al, 2019).…”

“…Parasite genomics has the potential to help us better understand malaria epidemiology by uncovering population structure and gene flow, providing insight into changes in the parasite population including how parasites move between regions (Neafsey et al, 2021). Genomics has previously been used to study importation and transmission chains in other low transmission settings in Africa and elsewhere (H. H. Chang et al, 2019; Fola et al, 2023; Morgan et al, 2020; Patel et al, 2014; Roh et al, 2019; Sane et al, 2019). Previously, we had investigated the importation of malaria into Zanzibar from the mainland using whole genome sequencing, showing highly similar populations within the mainland and within the archipelago, but also identifying highly related parasite pairs between locations suggesting a role for importation (Morgan et al, 2020).…”

“…Genomics has previously been used to study importation and transmission chains in other low transmission settings in Africa and elsewhere (H. H. Chang et al, 2019; Fola et al, 2023; Morgan et al, 2020; Patel et al, 2014; Roh et al, 2019; Sane et al, 2019). Previously, we had investigated the importation of malaria into Zanzibar from the mainland using whole genome sequencing, showing highly similar populations within the mainland and within the archipelago, but also identifying highly related parasite pairs between locations suggesting a role for importation (Morgan et al, 2020). However, this work lacked sufficient samples to assess transmission of parasites within Zanzibar.…”

Systematic bias in malaria parasite relatedness estimation

“…As such, relatedness analyses reflect the recent, context-specific history of malaria parasites, generating epidemiologically relevant insight. For example, analyses of relatedness have been used to evaluate and inform efforts to reduce transmission [5,6,7], to elucidate population connectivity on granular spatiotemporal scales [8,9,10,11,12], to characterise the structure of inbred populations [13,14], to resolve transmisson heterogeneity [15], and to identify regions of the parasite genome subject to recent selective pressure [14,16,17]. Relatedness has further applications in clinical trials of antimalarial drugs, i.e., in the classification of Plasmodium falciparum reinfection and recrudescence [18] and of Plasmodium vivax reinfection, recrudescence and relapse [19,20].…”