The origins and relatedness structure of mixed infections vary with local prevalence of P. falciparum malaria

McVean, Gil; Hendry, Jason A.; Almagro-Garcia, Jacob; Pearson, Richard D.; Amato, Roberto; Miles, Alistair; Weiss, Daniel J.; Tcd., Lucas; Nguyen, Michele; Gething, Peter W.; Kwiatkowski, Dominic

doi:10.7554/elife.40845

Cited by 58 publications

(81 citation statements)

References 47 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This within-host diversity poses technical challenges but also provides information on transmission dynamics. Approximately half of isolates from both the mainland and Zanzibar represent mixed infections (COI > 1), similar to estimates in Malawian parasites with similar ancestry [15]. It is clear that a widely-used heuristic index (F ws ) is qualitatively consistent with COI estimated by haplotype deconvolution [52], but has limited discriminatory power in the presence of related lineages in the same host.…”

Section: Discussionmentioning

confidence: 55%

“…A major obstacle to studying IBD in microorganisms, and in particular malaria, is the presence of multiple clones in a single infection. 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 now make it tractable to conduct population genetic analysis of malaria in regions of higher transmission, where infections are often polyclonal.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Morgan

Brazeau

Ngasala

et al. 2020

Malar J

View full text Add to dashboard Cite

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: Whole-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. Results: Significant 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. 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.

show abstract

Section: Discussionmentioning

confidence: 55%

mentioning

confidence: 99%

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

Morgan

Brazeau

Ngasala

et al. 2020

Malar J

View full text Add to dashboard Cite

show abstract

“…11,13,14 McVean and colleagues have developed a computational method for deconvolution of the haplotypic structure of mixed infections, allowing analysis of the pedigree structure of parasites that are cotransmitted by the same mosquito. 49 Bahlo and colleagues have developed a different haplotype-based method to describe the relatedness structure of the parasite population and to identify new genomic loci with evidence of recent positive selection. 50 A recent report from the World Health Organisation highlights the need for improved surveillance systems in sustaining malaria control and achieving the long-term goal of malaria eradication.…”

Section: Discussionmentioning

confidence: 99%

“…A key area of methods development is quantification of within-host diversity 7,[41][42][43][44][45][46] , estimation of inbreeding 7,47 , and deconvolution of mixed infections into individual strains. 48,49 The data have also been used to develop and test methods for estimating identity by descent 50,51 , imputation 52 , typing structural variants 53 , designing other SNP genotyping platforms 54 and data visualisation 8,55 . In a companion study we performed whole genome sequencing of experimental genetic crosses of P. falciparum, and this provided a benchmark to test the accuracy of our genotyping methods, and to conduct an in-depth analysis of indels, structural variants and recombination events which are complicated to ascertain in these population genetic samples 56 .…”

Section: Introductionmentioning

confidence: 99%

An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples

Pearson

Amato

Kwiatkowski

2019

Preprint

Self Cite

View full text Add to dashboard Cite

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination. MethodsAll samples in this study were derived from blood samples obtained from patients with P. falciparum malaria, collected with informed consent from the patient or a parent or guardian. At each location, sample collection was approved by the appropriate local and institutional ethics committees. The following local and institutional committees gave ethical approval for the partner studies:Standard laboratory protocols were used to determine DNA quantity and proportion of human DNA in each sample as previously described 7,56 .

show abstract

mentioning

confidence: 99%

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

Morgan

Brazeau

Ngasala

et al. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

The origins and relatedness structure of mixed infections vary with local prevalence of P. falciparum malaria

Cited by 58 publications

References 47 publications

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

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

An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples

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

Contact Info

Product

Resources

About