SNP data: Comparison of molecular surveillance methods to assess changes in the population genetics of Plasmodium falciparum in high-transmission

Genetic diversity and population structure of Plasmodium falciparum are assessed here using three established methods (i) SNP barcoding (panel of 24-biallelic loci), (ii) microsatellite genotyping (panel of 12-multiallelic loci), and (iii) varcoding (fingerprinting var gene diversity, akin to microhaplotyping) to identify changes in parasite population genetics in response to a short-term indoor residual spraying (IRS) intervention. Typical of high seasonal transmission in Africa, multiclonal infections were found in 82.3% (median 3; range 1–18) and 57.8% (median 2; range 1–12) of asymptomatic individuals pre- and post-IRS, respectively, in Bongo District, Ghana. Since directly phasing multilocus haplotypes for population genetic analysis is not possible for biallelic SNPs and microsatellites, we chose 200 low-complexity infections for analysis. Each genotyping method presented a different pattern of change in population diversity and structure as a consequence of variability in usable data and the relative polymorphism of the molecular markers (SNPs < microsatellites < var). In terms of neutral variation, the 24-SNP barcode was the least informative, largely due to the bi-allelic nature of SNPs leading to a high proportion of double-allele calls (DACs), whereas multiallelic microsatellites showed high haplotype diversity with ten markers but no measurable change in population structure after IRS. Varcoding provided the most informative and nuanced description of changes in population structure, showing high diversity with a subtle but measurable change to less related var repertoires as a result of the IRS intervention. Relative performance, suitability, and cost-effectiveness of the methods relevant to local malaria elimination in high-transmission endemic areas are discussed.