Plasmodium falciparum antimalarial resistance in Angola: a systematic review

Malaria remains a major health challenge in Angola, where Plasmodium falciparum accounts for most cases and deaths. Although artemisinin-based combination therapies (ACTs) have been the recommended first-line treatments in the country since 2006, the emergence of resistance-associated mutations in Africa raises concerns. We conducted a systematic review of molecular markers of antimalarial drug resistance in Angola (2000-2024) to map their prevalence and distribution at the provincial level. Following PRISMA 2020 guidelines, we searched PubMed, Scopus and Web of Science for studies on P. falciparum resistance markers: polymorphisms in pfcrt, pfdhfr, pfdhps, pfmdr1, pfk13, or copy number variation (CNV) in pfmdr1 and pfpm2/3. Data on mutations, prevalence, and geographic distribution was extracted and summarized. 20 studies met our inclusion criteria. The chloroquine-resistant pfcrt CVIET haplotype persisted in northern and coastal provinces, while the SP-resistant pfdhfr/pfdhps IRNGE haplotype was detected in Cabinda and Zaire. No validated pfk13 mutations linked to artemisinin resistance were reported. Pfmdr1 analyses showed declining 86Y and 1246Y mutation frequencies, with wild-type NYD and NFD haplotypes predominating. Low pfmdr1 and pfpm2 CNV prevalence was reported, though recent data indicate emerging amplification in southern Angola. Research was concentrated in Benguela, Luanda, Lunda Sul, and Zaire, leaving large geographic gaps country-wise. Resistance markers in Angola show heterogeneous provincial distribution. Expanded molecular surveillance, particularly in underrepresented provinces and among pregnant women, is critical to safeguard ACT efficacy and guide national malaria control strategies.