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

## TL;DR

Adding a low dose of primaquine to artemether-lumefantrine treatment significantly reduces malaria transmission by clearing gametocytes faster and blocking infectivity to mosquitoes.

## Contribution

Demonstrates that combining artemether-lumefantrine with a single low-dose primaquine effectively accelerates gametocyte clearance and blocks post-treatment transmission.

## Key findings

- AL + SLD-PQ reduced gametocyte prevalence to 0% by day 7, compared to 12.2% with AL alone.
- Mosquito infectivity was 28.6% with AL-only on day 3, but only 6.8% with AL + SLD-PQ.
- Submicroscopic gametocytemia contributed to residual transmission in the AL-only group.

## Abstract

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.