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

Abstract

We here analyze data from the first year of an ongoing nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal. The analysis is based on 1097 samples collected at health facilities during passive malaria case detection in 2019; it provides a baseline for analyzing parasite genetic metrics as they vary over time and geographic space. The study's goal was to identify genetic metrics that were informative about transmission intensity and other aspects of transmission dynamics, focusing on measures of genetic relatedness between parasites. We found the best genetic proxy for local malaria incidence to be the proportion of polygenomic infections (those with multiple genetically distinct parasites), although this relationship broke down at low incidence. The proportion of related parasites was less correlated with incidence while local genetic diversity was uninformative. The type of relatedness could discriminate local transmission patterns: two nearby areas had similarly high fractions of relatives, but one was dominated by clones and the other by outcrossed relatives. Throughout Senegal, 58% of related parasites belonged to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci and at one novel locus, reflective of ongoing selection pressure.

Fig. 1. Map of Senegal showing incidence and location of sample collection sites.

a Map of Senegal showing annual malaria incidence per 1000; b location of sample collection sites with relative sample size by site. Inset expands the Dakar region.

Fig. 2. Genetic relatedness within and between study sites.

a Mean pairwise genetic diversity measured within (triangle) and between (stars) study sites as a function of distance (kilometers, km). Gray dots give values for individual site pairs, while triangles give weighted averages in 100 km bins. b Pairwise relatedness within and between sites, indicated by area of circles and thickness of lines, respectively. c Mean pairwise relatedness within (triangle) and between (stars) study sites as a function of distance (km). d Partial relatedness vs. clonality for each study site (see Table 1 for site codes and sample sizes; error bars represent 68% confidence intervals, see Methods). e Networks of related parasites in Diourbel (left) and Touba (right). The two study sites in Diourbel are indicated by circles (SES) and squares (SMS). Line thickness is proportional to the degree of relatedness, with the thickest lines indicating clones.

Fig. 3. Relationship between genetic metrics and incidence.

a Relationship between pairwise relatedness and reported incidence at study sites (see Table 1 for site codes and sample sizes). b Relationship between polygenomic fraction and reported site incidence. In a and b, error bars represent 68% confidence intervals arising from sampling error (see Methods for details).

Fig. 4. Related parasites share genomic regions of reduced diversity consistent with a selective sweep.

Parasite relatedness between study sites. a Network of relatedness between all sequenced samples (clones excluded). Samples are colored by study site as indicated on the inset map. b The fraction of sample pairs that are IBD as a function of genomic position, split into samples that are (“within cluster”) or are not (“outside cluster”) part of the large network of related parasites. The four examples shown are a selective sweep around the known drug resistance locus at pfcrt (crt, green dotted line); a suspected sweep on chromosome 6 surrounding the aat1 locus (brown dotted line); a possible sweep on chromosome 12 containing the gch1 locus (pink dotted line); a possible unreported sweep on chromosome 11.