Abstract
Plasmodium falciparum malaria remains a leading cause of mortality in Angola, with emerging antimalarial resistance threatening treatment and prevention strategies. Efficacy of artemether-lumefantrine, one of the country's preferred malaria treatments, has been reported below 90% in two provinces, underscoring the need for routine resistance surveillance and efficacy monitoring to guide policy decisions. Between March and July 2023, dried blood spots and demographic data were collected from P. falciparum-positive participants at 16 health facilities across 8 provinces. Multiplexed amplicon deep sequencing was used to characterize single nucleotide polymorphisms in 12 genes linked with resistance, estimate allele frequencies, and detect co-infecting non-falciparum Plasmodium species. Sequence data from 817 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%), while the quintuple dhps/dhfr haplotype, linked to sulfadoxine-pyrimethamine (SP) resistance, was very prevalent (>40% of samples). In the northwest, the sextuple dhps/dhfr haplotype, a marker of higher SP resistance, was most prevalent in Zaire (14.2%). The crt CVIET haplotype, associated with chloroquine resistance, had a national prevalence of 15.9%, detected in over 48% of samples from Zaire and Uíge. The mdr1 N86 genotype, linked to reduced lumefantrine susceptibility, was widespread, detected in 99.3% of samples. Co-infections of P. falciparum and non-falciparum species were rare with no clear geographic distribution. No P. vivax co-infections were detected. These findings highlight the need for continued monitoring to safeguard treatment efficacy, reinforcing the importance of molecular surveillance in malaria control strategies.