MD-PhD Program, University of North Carolina at Chapel Hill, Chapel Hill, United States
Nicholas F Brazeau
MD-PhD Program, University of North Carolina at Chapel Hill, Chapel Hill, United States
Mwinyi Msellem
Research Division, Ministry of Health, Zanzibar, United Republic of Tanzania
Billy E Ngasala
Department of Parasitology and Medical Entomology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, United Republic of Tanzania; Global Health and Migration Unit, Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya
Robert Verity
MRC Centre for Global Infectious Disease Analysis, Imperial College London, London, United Kingdom
Safia Mohammed
Zanzibar Malaria Elimination Program (ZAMEP), Zanzibar, United Republic of Tanzania
Shija J Shija
Zanzibar Malaria Elimination Program (ZAMEP), Zanzibar, United Republic of Tanzania
Lwidiko E Mhamilawa
Department of Parasitology and Medical Entomology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, United Republic of Tanzania; Global Health and Migration Unit, Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, United States
Anders Björkman
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Global Public Health, Karolinska Institute, Stockholm, Sweden
Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, United States; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, United States; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States
Background: The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission. Methods: To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018. Results: Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low-level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes. Conclusions: Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors. Funding: This research was funded by the National Institutes of Health, grants R01AI121558, R01AI137395, R01AI155730, F30AI143172, and K24AI134990. Funding was also contributed from the Swedish Research Council, Erling-Persson Family Foundation, and the Yang Fund. RV acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 program supported by the European Union. RV also acknowledges funding by Community Jameel.
