Plasmodium falciparum population genomics in malaria-eliminating districts in South Africa: Implications for malaria elimination efforts
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1
ARMMOR, National Institute for Communicable Disease, Johannesburg, South Africa
2
WRIM, University of Witwatersrand, Johannesburg, South Africa
3
UP Sustainable Institute for Malaria Control, University of Pretoria, Pretoria, South Africa
4
Malaria Elimination Initiative, Global Health Group, University of California San Francisco, San Francisco, United States
5
EPPIcenter Research Program, Department of Medicine, University of California San Francisco, San Francisco, United States
6
ISGlobal, Barcelona, Spain
Popul. Med. 2026;8(Supplement Supplement 1):A202
ABSTRACT
ABSTRACT:
South Africa has made significant progress towards reducing local malaria transmission in certain areas. However, elimination is proving challenging as focal pockets of residual transmission persist. Currently, there is limited clarity on the extent of local transmission and whether it is sustained by importation or by asymptomatic carriage within the community. This study investigated the genetic diversity of parasites from districts targeting elimination and explored the feasibility and value of incorporating locally generated genomic data into routine malaria surveillance to support evidence-based decision-making by national malaria control programs. Dried blood spots and positive malaria rapid diagnostic tests were routinely collected from primary healthcare facilities and mobile surveillance units in eliminating districts of KwaZulu-Natal and Mpumalanga Provinces during the 2021/2022 and 2022/2023 malaria seasons. Samples confirmed as falciparum-positive by qPCR were sequenced using a 274-target amplicon sequencing panel (Multiplex Amplicons for Drugs, Diagnostics, Diversity, and Differentiation using High Throughput Targeted Resequencing, MAD4HatTeR). Markers of artemisinin partial resistance were rare. However, polyclonal infections were prevalent across all districts (58% of all samples) with similar levels of polyclonality in infections detected at healthcare facilities and in the community. Although population structure was low, identity-by-descent analysis revealed that 34% of cases were significantly related to at least one other case. We observed clustering of cases in both provinces, indicating potential local transmission. Clusters were larger in Mpumalanga, suggesting that local transmission is more sustained in that province. This study confirmed the feasibility of incorporating genomics into routine malaria surveillance to support evidence-based decision-making. However, inferring epidemiological processes from genetic diversity and relatedness data is challenging and requires more evidence including development of statistical frameworks to more accurately infer epidemiologic parameters. Additionally, dense sampling along shared border regions is needed to elucidate transmission networks and classify malaria cases more accurately.