Geographical Heterogeneity in Antimalarial Resistance Markers by Genomic Surveillance in Angola, 2023

Plasmodium falciparum malaria remains a leading cause of mortality in Angola, with emerging antimalarial resistance threatening treatment and prevention strategies. Efficacy of artemether-lumefantrine has been reported below 90% in two provinces, underscoring the need for routine resistance surveillance. This study aimed to provide a geographically comprehensive and up-to-date overview of antimalarial drug resistance markers in Angola. Between March and July 2023, dried blood spots and demographic data were collected from P. falciparum-positive participants at 14 health facilities across 7 provinces. Multiplexed amplicon sequencing was used to characterize single nucleotide polymorphisms in 12 genes linked with resistance, estimate allele frequencies, and detect coinfecting non-falciparum Plasmodium species. Sequence data from 820 samples revealed significant geographic variation in resistance markers. In the southeast, artemisinin partial resistance markers (k13 P574L, P441L) were detected at very low prevalence (<0.1%), whereas the quintuple dhps/dhfr haplotype, linked to sulfadoxine-pyrimethamine resistance, was very prevalent (>35% of samples). In the northwest, the sextuple dhps/dhfr haplotype, a marker of higher sulfadoxine-pyrimethamine resistance, was most prevalent in the Zaire province (14.2%). The chloroquine resistance marker crt C72/V73/M74I/N75E/K76T (CVIET) haplotype had a national prevalence of 17.7%, detected in over 48% of samples from the northern sites. The mdr1 N86 genotype, linked to reduced lumefantrine susceptibility, was detected in 99.2% of samples. Coinfections of P. falciparum and non-falciparum species were rare, with no Plasmodium vivax coinfections detected. These findings highlight the need for continued monitoring to safeguard treatment efficacy, reinforcing the importance of molecular surveillance in malaria control strategies.