Modeling Malaria Rebound After Mass Drug Administration: The Role of Importation and Waning Immunity in Lake Victoria, Kenya

Background: Mass Drug Administration (MDA) is a WHO-recommended strategy for accelerating malaria elimination. However, its effectiveness in highly mobile populations remains uncertain. Studies show rapid parasitological rebound after cessation of MDA, this suggests that drug-based clearance alone is insufficient in interconnected settings. Although the resurgence is attributed to a combination of waning chemoprophylaxis and parasite importation, the relative contribution of these mechanisms and the quantitative conditions required for sustained elimination remain poorly defined. Methods: We developed a stochastic model of Susceptible-Infected-Recovered-Susceptible (SIRS) compartmentalized to a longitudinal PCR prevalence trial Ngodhe Island (artemisinin-piperaquine + primaquine) in 2016. Based on Bayesian estimation of transmission potential and daily importation rates, we simulated scenarios for a period of 4 years (2016–2019). We compared the epidemiological effects of increasing the MDA schedules (annual versus bimodal, which is two rounds during the two low transmission seasons) and measured the combined effect of integrating enhanced vector control coverage (90% LLIN coverage), port-of-entry screening (80% reduction in importation) and reactive focal MDA. Results: Model simulations have indicated that an intensifying MDA schedule (annual versus bimodal) is not associated with a proportional decrease in mean prevalence, the mean prevalence plateaus at 4.1% as a result of an importation induced equilibrium. This finding implies that, without reducing external seeding, the system will have an equilibrium at the pace of importation faster than the drug pulses can suppress transmission rates. Single-intervention strategies did not meet elimination thresholds but a combination strategy with bimodal MDA combined with improved vector control and importation screening exhibited a non-linear type of intervention combination, as it was able to drive and maintain mean prevalence below the pre-elimination threshold (< 1%). Conclusions: With high mobility like in Ngodhe Island, increasing the frequency of mass treatment is not a viable solution to suppress the reintroduction of parasites. Our results provide mechanistic evidence that elimination requires a shift from the current mono-therapeutic scaling to interventions that are multi-modal. The rollout of importation control and vector control should be made a priority alongside MDA, as chemoprevention alone is not sufficient in interrupting transmission.