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.