Household clustering and seasonal genetic variation ofPlasmodium falciparumat the community-level in The Gambia
Authors: Guery Marc-Antoine , Ceesay Sukai , Drammeh Sainabou , Jaiteh Fatou K , d’Alessandro Umberto , Bousema Teun , Conway David J , Claessens Antoine 
Published: August 2024

AbstractUnderstanding the genetic diversity and transmission dynamics ofPlasmodium falciparum, the causative agent of malaria, is crucial for effective control and elimination efforts. In some endemic regions, malaria is highly seasonal with no or little transmission during up to 8 months, yet little is known about how seasonality affects the parasite population genetics. Here we conducted a longitudinal study over 2.5 years on 1516 participants in the Upper River Region of The Gambia. With 425P. falciparumgenetic barcodes genotyped from asymptomatic infections, we developed an identity by descent (IBD) based pipeline and validated its accuracy against 199 parasite genomes sequenced from the same isolates. Genetic relatedness between isolates revealed a very low inbreeding level, suggesting continuous recombination among parasites rather than the dominance of specific strains. However, isolates from the same household were six-fold more likely to be genetically related compared to those from other villages, suggesting close transmission links within households. Seasonal variation also influenced parasite genetics, with most differentiation occurring during the transition from the low transmission season to the subsequent high transmission season. Yet chronic infections presented exceptions, including one individual who had a continuous infection by the same parasite genotype for at least 18 months. Our findings highlight the burden of asymptomatic chronic malaria carriers and the importance of characterising the parasite genetic population at the community-level. Most importantly, ‘reactive’ approaches for malaria elimination should not be limited to acute malaria cases but be broadened to households of asymptomatic carriers.Author SummaryMalaria, caused by the parasitePlasmodium falciparum, remains a significant health challenge, particularly in regions like The Gambia where transmission is seasonal. Our study explored how seasonal changes impact the genetic diversity and transmission patterns ofP. falciparumwithin communities. By tracking 1516 participants over 2.5 years and analyzing the genetic material of the parasites they carried, we discovered that malaria parasites in this region exhibit high genetic diversity, with frequent recombination events rather than dominance by specific strains. Interestingly, we found that parasites from individuals within the same household were much more likely to be genetically related, suggesting close transmission links within households. Seasonal shifts also influenced genetic relationships, with parasite populations becoming more diverse during peak transmission periods. Notably, one individual carried the same parasite strain for over a year without showing symptoms, highlighting the hidden reservoir of chronic malaria infections. Our findings suggest that malaria control strategies should extend beyond treating symptomatic cases to include household members of infected individuals, aiming to disrupt the wider transmission network within communities. This approach could be crucial for advancing malaria elimination efforts in regions with similar transmission dynamics.