Population dynamics and drug resistance mutations in Plasmodium falciparum on the Bijagós Archipelago, Guinea-Bissau

Abstract

Following integrated malaria control interventions, malaria burden on the Bijagós Archipelago has significantly decreased. Understanding the genomic diversity of circulating Plasmodium falciparum malaria parasites can assist infection control, through identifying drug resistance mutations and characterising the complexity of population structure. This study presents the first whole genome sequence data for P. falciparum isolates from the Bijagós Archipelago. Amplified DNA from P. falciparum isolates sourced from dried blood spot samples of 15 asymptomatic malaria cases were sequenced. Using 1.3 million SNPs characterised across 795 African P. falciparum isolates, population structure analyses revealed that isolates from the archipelago cluster with samples from mainland West Africa and appear closely related to mainland populations; without forming a separate phylogenetic cluster. This study characterises SNPs associated with antimalarial drug resistance on the archipelago. We observed fixation of the PfDHFR mutations N51I and S108N, associated with resistance to sulphadoxine-pyrimethamine, and the continued presence of PfCRT K76T, associated with chloroquine resistance. These data have relevance for infection control and drug resistance surveillance; particularly considering expected increases in antimalarial drug use following updated WHO recommendations, and the recent implementation of seasonal malaria chemoprevention and mass drug administration in the region.

Figure 1

Population structure analysis: (top) Principal component analysis demonstrating that the isolates from the Bijagós (in purple) cluster with other isolates from West Africa (in orange and yellow). Generated using pairwise genetic distance matrices containing 1,326,629 SNPs from 795 isolates. (bottom) Neighbour-Joining tree for the samples and SNPs described above. Isolates were sampled from Central Africa (Gabon, n = 57), West Africa (Ivory Coast n = 70, The Gambia n = 148, Bijagós Archipelago Guinea-Bissau (n = 15), East Africa (Kenya n = 138, Uganda n = 17), Southeast Africa (Malawi n = 149, Madagascar n = 24), South Central Africa (DRC n = 150) and Horn of Africa (Eritrea n = 27). Bijagós isolates (indicated with purple arrows) are found interspersed with samples from West Africa (orange and yellow).

Figure 2

Map showing the proximity of the Bijagós Archipelago to the other countries within this dataset, and the number of SNPs with F_ST > 0.75 for each country comparison.

Figure 3

(top) Ancestry analysis of P. falciparum isolates from (B) the Bijagós Archipelago, (CA) Central Africa, (EA) East Africa, (H) Horn of Africa, (SCA) South Central Africa, (SEA) Southeast Africa and (WA) West Africa. Individual isolates are plotted along the x-axis, with ancestry coefficients on the y-axis. The number of ancestral populations, K, used in this analysis was K = 5. (bottom) Principal component analysis generated using pairwise genetic distance matrices. This is coloured by the maximum K value for each isolate.