The Effect of Artemether–Lumefantrine Combined with a Single Dose of Primaquine on Plasmodium falciparum Gametocyte Clearance and Post-Treatment Infectivity to Anopheles arabiensis

Background: Malaria remains a major public health concern in Africa, due to the persistence of Plasmodium falciparum gametocytes that sustain transmission post treatment. This study evaluated the effects of artemether-lumefantrine (AL) alone compared with AL combined with a single low-dose of primaquine (SLD-PQ) on gametocyte clearance and infectivity to Anopheles arabiensis post treatment. Methods: A prospective cohort and entomological study were conducted from January to September 2025 in Northwest Ethiopia. Ninety-six microscopically confirmed cases of P. falciparum gametocytemia mono-infection were proportionally assigned to both treatment groups. Follow-up assessments were conducted on days 3, 7, 14, and 28, and mixed-species infections were assessed using molecular diagnostic assays. Additionally, membrane feeding assays (MFAs) were performed to evaluate mosquito infectivity post treatment. Results: Gametocyte prevalence declined faster with AL + SLD-PQ (15.2% on day 3; 0% by day 7) compared to AL alone (28.9% on day 3: p = 0.001; 12.2% by day 7: p = 0.033). Higher baseline gametocyte density strongly predicted mosquito infection (95% in high vs. 59% moderate and 33% low). On day 3 post treatment, 28.6% of cases treated with AL only showed confirmed mosquito infection, compared to 6.8% in the AL + SLD-PQ group (p = 0.001). By day 7, 7.3% of cases remained infectious in the AL-only group, while none were detected in the AL+ SLD-PQ group (p = 0.01). Conclusions: High baseline gametocyte density strongly correlated with increased infectivity. Adding SLD-PQ markedly accelerates gametocyte clearance and completely blocks post-treatment transmission. Submicroscopic gametocytemia contributed to residual transmission in the AL-only group. Incorporation of SLD-PQ alongside AL, in line with WHO recommendations, is advised to enhance post-treatment transmission blocking, with continued surveillance.