Mapping Antimalarial Drug Resistance in Mozambique: a systematic review of Plasmodium falciparum Genetic Markers Post-ACT Implementation

Malaria continues to be a significant public health burden in many tropical and subtropical regions. Mozambique ranks among the top countries affected by malaria, where it is a leading cause of morbidity and mortality, accounting for 29% of all hospital deaths in the general population and 42% of deaths amongst children under five. This review presents a comparative analysis of data on five critical genes associated with antimalarial drug resistance: pfmdr1, pfcrt, pfk13, pfdhfr and pfdhps, along with copy number variation (CNV) in genes pfmdr1 and pfpm2/3. These are genes associated with parasite response to currently used for antimalarials to treat uncomplicated P. falciparum malaria in Mozambique. The review synthesizes data collected from published studies conducted in Mozambique after the introduction of ACTs (2006) up to June 2024, highlighting the presence or absence of mutations in these genes across Mozambique. We aimed at mapping the prevalence and distribution of these molecular markers, across the country, in order to contribute to the development of targeted interventions to sustain the efficacy of malaria treatments in Mozambique. Four databases were used to access the articles: PubMed, Science direct, Scopus and Google scholar. The search strategy identified 132 studies addressing malaria and antimalarial resistance. Of these, 112 were excluded for various reasons, leaving 20 studies to be included in this review. Children and pregnant women represent the majority of target groups in studies on all types of antimalarials. Most studies (87.5%) were conducted in the provinces of Maputo and Gaza. The primary alleles re-ported were pfcrt CVMNK, and in the most recent data, its wild-type form was found in the majority of patients. Low prevalence of mutations in the pfk13 gene, were identified reflecting the effectiveness of ACTs. In pfk13 only mutation A578S was reported, in Niassa and Tete. Regarding CNVs were observed in studies carried out in the south of Mozambique, for pfmdr1 with a frequency of 1.1-5.1% and pfpm2 with a frequency of 1.1-3.4%. This review indicates that molecular markers linked to malaria resistance show considerable variation across provinces in Mozambique, with most up-to-date data accessible for Maputo and Gaza. In contrast, provinces such as Zambezia and Inhambane have limited data on several genes, while Nampula lacks data on all drug resistance markers. Our review reveals that gene mutations associated with antimalarial resistance, vary considerably by province in Mozambique, with more up-to-date data available for Maputo and Gaza. Other provinces, including Zambezia, Inhambane, and Cabo Delgado, have limited data on several genes, while Nampula entirely lacks data on all drug resistance molecular markers.