Abstract
BACKGROUND: Despite efforts to eliminate malaria in Sao Tome and Principe (STP), cases have recently increased. Understanding residual transmission structure is crucial for developing effective elimination strategies. METHODS: This study collected surveillance data and generated amplicon sequencing data from 980 samples between 2010 and 2016 to examine the genetic structure of the parasite population. RESULTS: Here we show that the mean multiplicity of infection (MOI) is 1.3, with 11% polyclonal infections, indicating low transmission intensity. Temporal trends of these genetic metrics do not align with incidence rates, suggesting that changes in genetic metrics may not straightforwardly reflect changes in transmission intensity, particularly in low transmission settings where genetic drift and importation have a substantial impact. While 88% of samples are genetically linked, continuous turnover in genetic clusters and changes in drug-resistance haplotypes are observed. Principal component analysis reveals some STP samples are genetically similar to those from Central and West Africa, indicating possible importation. CONCLUSIONS: These findings highlight the need to prioritize several interventions, such as targeted interventions against transmission hotspots, reactive case detection, and strategies to reduce the introduction of new parasites into this island nation as it approaches elimination. This study also serves as a case study for implementing genetic surveillance in a low transmission setting.