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

Abstract

The Zanzibar archipelago of Tanzania has become a low-transmission area forPlasmodium 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. To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 391P. falciparumisolates collected across Zanzibar and in Bagamoyo District on the coastal mainland from 2016-2018. Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, in Zanzibar the parasite population exhibits microstructure due to rapid decay of parasite relatedness over very short distances. This, along with highly related pairs withinshehias, suggests ongoing low level local transmission. We also identified highly related parasites acrossshehiasthat 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. Our data support that importation remains a main source of genetic diversity and contribution to the parasite population on 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 for malaria reemergence due to susceptible hosts and competent vectors.

Genetic surveillance reveals low, sustained malaria transmission with clonal replacement in Sao Tome and Principe

“…However, a gap remains due to the lack of integration between epidemiological metadata and genomic information, which is crucial for understanding the structure of residual transmission in STP. With advancements and cost reductions in sequencing technology, an increasing number of countries are adopting genomic surveillance approaches to track transmission dynamics, potential importations, and the spread of drug-resistant parasites 14,15,16,17,18,19,20,21,22,23,24,25,26,27 . Several genetic metrics have been proposed to estimate malaria transmission, including the multiplicity of infection (MOI-which denotes the number of genetically distinct parasite strains within an individual), within-host relatedness, Fws, and pairwise relatedness between infections 22,28,29,30,31,32,33 .…”

High-Throughput Genotyping ofPlasmodium vivaxin the Peruvian Amazon via Molecular Inversion Probes

“…Transmission of P. vivax is more complex due to the presence of hypnozoites in the liver, which cause disease relapse without a new infectious mosquito bite 3 , and earlier gametocytogenesis than P. falciparum 4 , meaning that it can be transmitted earlier in an infection, even among asymptomatic patients 5 . Genomic epidemiology is a powerful tool for understanding parasite biology and transmission, but most work has been done in P. falciparum [6][7][8][9][10][11] . Given the challenging biology impeding control 12 , there is an urgent need for the development of high-throughput genotyping methods to better understand this neglected parasite.Genomic epidemiology studies of P. falciparum using whole genome sequencing (WGS), molecular inversion probes (MIPs), and amplicon sequencing have generated useful data to support malaria elimination by identifying parasite population structure 6,7 , importation and transmission networks and connectivity 7 , and the geographical spread of antimalarial 6,7,[9][10][11][13][14][15] and diagnostic resistance 16 .…”

“…Transmission of P. vivax is more complex due to the presence of hypnozoites in the liver, which cause disease relapse without a new infectious mosquito bite 3 , and earlier gametocytogenesis than P. falciparum 4 , meaning that it can be transmitted earlier in an infection, even among asymptomatic patients 5 . Genomic epidemiology is a powerful tool for understanding parasite biology and transmission, but most work has been done in P. falciparum [6][7][8][9][10][11] . Given the challenging biology impeding control 12 , there is an urgent need for the development of high-throughput genotyping methods to better understand this neglected parasite.…”