Multiplexed ddPCR-amplicon sequencing reveals isolated Plasmodium falciparum populations amenable to local elimination in Zanzibar, Tanzania

Aurel Holzschuh (), Anita Lerch, Inna Gerlovina, Bakar S. Fakih, Abdul-wahid H. Al-mafazy, Erik J. Reaves, Abdullah Ali, Faiza Abbas, Mohamed Haji Ali, Mohamed Ali Ali, Manuel W. Hetzel, Joshua Yukich and Cristian Koepfli ()
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Aurel Holzschuh: University of Notre Dame
Anita Lerch: University of Notre Dame
Inna Gerlovina: University of California
Bakar S. Fakih: Swiss Tropical and Public Health Institute
Abdul-wahid H. Al-mafazy: Research Triangle Institute (RTI) International
Erik J. Reaves: U.S. Centers for Disease Control and Prevention, President’s Malaria Initiative
Abdullah Ali: Zanzibar Malaria Elimination Programme
Faiza Abbas: Zanzibar Malaria Elimination Programme
Mohamed Haji Ali: Zanzibar Malaria Elimination Programme
Mohamed Ali Ali: Zanzibar Malaria Elimination Programme
Manuel W. Hetzel: Swiss Tropical and Public Health Institute
Joshua Yukich: Tulane University
Cristian Koepfli: University of Notre Dame

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Zanzibar has made significant progress toward malaria elimination, but recent stagnation requires novel approaches. We developed a highly multiplexed droplet digital PCR (ddPCR)-based amplicon sequencing method targeting 35 microhaplotypes and drug-resistance loci, and successfully sequenced 290 samples from five districts covering both main islands. Here, we elucidate fine-scale Plasmodium falciparum population structure and infer relatedness and connectivity of infections using an identity-by-descent (IBD) approach. Despite high genetic diversity, we observe pronounced fine-scale spatial and temporal parasite genetic structure. Clusters of near-clonal infections on Pemba indicate persistent local transmission with limited parasite importation, presenting an opportunity for local elimination efforts. Furthermore, we observe an admixed parasite population on Unguja and detect a substantial fraction (2.9%) of significantly related infection pairs between Zanzibar and the mainland, suggesting recent importation. Our study provides a high-resolution view of parasite genetic structure across the Zanzibar archipelago and provides actionable insights for prioritizing malaria elimination efforts.

Date: 2023
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DOI: 10.1038/s41467-023-39417-1

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