Antimalarial Drug Resistance Mechanisms and Treatment Outcomes in Sub‑Saharan African Populations

Nalongo Bina K.

Faculty of Medicine Kampala International University Uganda

ABSTRACT

Malaria remained a leading cause of morbidity and mortality in Sub‑Saharan Africa, where Plasmodium falciparum demonstrates increasing resistance to multiple antimalarial agents. The molecular basis of this resistance involved complex genetic mutations affecting drug targets, transporters, and metabolic pathways, with significant implications for treatment efficacy across diverse African populations. This review aims to synthesized current understanding of antimalarial drug resistance mechanisms in Sub‑Saharan Africa and evaluated their impact on clinical treatment outcomes, with emphasis on artemisinin‑based combination therapies and partner drugs. A comprehensive analysis of peer‑reviewed literature examining molecular resistance markers, biochemical mechanisms, pharmacogenetic factors, and clinical efficacy data from Sub‑Saharan African populations was conducted. Resistance to chloroquine and sulfadoxine‑pyrimethamine is widespread, mediated primarily by mutations in pfcrt, pfmdr1, pfdhfr, and pfdhps genes. Partial artemisinin resistance, characterized by kelch13 mutations, remained rare but surveillance data indicated emerging concerns in East Africa. Partner drug resistance threatened artemisinin‑based combination therapy effectiveness, with piperaquine and lumefantrine showing reduced efficacy in specific regions. Population‑specific factors including cytochrome P450 polymorphisms, nutritional status, and transmission intensity modulated treatment responses. Molecular surveillance revealed geographic heterogeneity in resistance allele frequencies, correlating with variable treatment failure rated across the continent. Antimalarial drug resistance in Sub‑Saharan Africa presented a multifaceted challenge requiring integrated molecular surveillance, individualized treatment approaches, and development of novel therapeutic strategies to maintain effective malaria control.

Keywords: Antimalarial resistance, Plasmodium falciparum, Artemisinin combination therapy, Molecular markers, Treatment failure

CITE AS: Nalongo Bina K. (2026). Antimalarial Drug Resistance Mechanisms and Treatment Outcomes in Sub Saharan African Populations. IDOSR JOURNAL OF BIOCHEMISTRY, BIOTECHNOLOGY AND ALLIED FIELDS 11(1):89-94.  https://doi.org/10.59298/IDOSR/JBBAF/2026/1028994