Estimating the overall effect of a mass drug administration strategy for malaria in Los Chiles, Costa Rica: One-year target trial emulation with synthetic controls

Background Mass drug administration (MDA) is a WHO-recommended strategy for the elimination of Plasmodium falciparum malaria in low-transmission settings close to elimination. After achieving zero autochthonous cases between 2013 and 2015, Costa Rica experienced a resurgence, primarily of P. falciparum, prompting an MDA intervention in 2023 in the Los Chiles focus. We evaluate its impact on the incidence of autochthonous malaria. Methods An MDA with two cycles of chloroquine (25 mg/kg per cycle, spaced seven weeks apart) was implemented between April—June 2023 in three localities (Medio Queso, Coquital, and San Gerardo) within the Los Chiles focus. We use a cluster-target trial emulation to estimate the overall average treatment effect on the treated (ATT) under an intention-to-treat approach. We use generalized synthetic control methods (GSCM) to construct a counterfactual for the intervened localities, using malaria surveillance data from January 2021 to April 2024. Our primary outcome was the autochthonous malaria case count at 1, 3, 6, and 12 months post-intervention. Results We found that the MDA achieved 93.3% coverage across the two cycles (4,316/4,624 people received at least one dose). The first cycle had 77.3% coverage and the second 51.2%, achieving 68.1% adherence (full treatment in at least one cycle) and 20.4% in both cycles. Following the intervention, autochthonous malaria cases in the treated localities decreased to zero in the first month and remained at zero throughout the 12-month follow-up period. Overall, we estimated that in the absence of MDA, cases would have persisted (approximately 3-4 cases/month). The strategy was associated with a significant reduction in cases, with an overall post-intervention Rate Ratio (RR) of 0.23 (95% CI: 0.13, 0.49) and an average reduction of 3.72 cases per period (95% CI: -7.2, -0.94) compared to the synthetic control. Conclusion We found that the chloroquine-based MDA strategy implemented in the Los Chiles focus was highly effective in interrupting autochthonous malaria transmission in the short and medium term. Our results suggest that MDA, when well-planned and implemented in a low transmission setting with a strengthened health system, can be a powerful tool to accelerate malaria elimination.