Plasmodium falciparum genomic surveillance reveals spatial and temporal trends, association of genetic and physical distance, and household clustering

Abstract

Molecular epidemiology using genomic data can help identify relationships between malaria parasite population structure, malaria transmission intensity, and ultimately help generate actionable data to assess the effectiveness of malaria control strategies. Genomic data, coupled with geographic information systems data, can further identify clusters or hotspots of malaria transmission, parasite genetic and spatial connectivity, and parasite movement by human or mosquito mobility over time and space. In this study, we performed longitudinal genomic surveillance in a cohort of 70 participants over four years from different neighborhoods and households in Thiès, Senegal—a region of exceptionally low malaria transmission (entomological inoculation rate less than 1). Genetic identity (identity by state, IBS) was established using a 24-single nucleotide polymorphism molecular barcode, identity by descent was calculated from whole genome sequence data, and a hierarchical Bayesian regression model was used to establish genetic and spatial relationships. Our results show clustering of genetically similar parasites within households and a decline in genetic similarity of parasites with increasing distance. One household showed extremely high diversity and warrants further investigation as to the source of these diverse genetic types. This study illustrates the utility of genomic data with traditional epidemiological approaches for surveillance and detection of trends and patterns in malaria transmission not only by neighborhood but also by household. This approach can be implemented regionally and countrywide to strengthen and support malaria control and elimination efforts.

Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal

“…Diourbel, on the other hand, is a smaller urban setting (estimated population around 100,000) that contains numerous large (500 -1000 individuals) religious boarding schools called daaras, where up to several hundred school-aged boys, many from elsewhere in Senegal, live communally. Previous work has shown evidence of distinct, genetically identical parasites among infections from individual daaras elsewhere in Senegal, consistent with local and focal transmission [10].…”

“…It already has a well-established role in tracking the spread of known drug resistance markers and detecting the appearance of new resistance alleles [6,7]. In low transmission settings, genetic data can determine whether new cases arise from ongoing local transmission or from importation, and it can potentially identify sources of imported parasites [8][9][10].…”

Superinfection plays an important role in the acquisition of complexPlasmodium falciparuminfections among femaleAnophelesmosquitoes

“…In particular, malaria molecular surveillance studies often rely on measures of parasite genetic diversity and relatedness to identify differences in transmission intensity or to uncover transmission dynamics such as spatial foci of transmission, but these studies also focus heavily on genotyping parasites in human infections [49][50][51] . This and other studies have demonstrated that mosquitoes are an important reservoir of parasite genetic diversity 52 .…”

High-throughput profiling of natural acquired humoral immune response to a large panel of known and novel full length ectodomain P. falciparum merozoite vaccine candidates under reduced malaria transmission

“…Study participants consisted of a total of 70 male patients with a median age of 11 (5-16) years, median parasitemia on the day of recruitment of 0.43(0.02-4.89)% and with a mean of 1 (0-5) number of past malaria infections (Table 1), described previously (Sy et al 2020). These participants were recruited from six neighborhoods of the Thiès region of Senegal.…”