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Genetic surveillance reveals low but sustained malaria transmission with clonal replacement in Sao Tome and Principe

Ying-An Chen,Peng-Yin Ng,Daniel Garcia-Ruiz,Aaron Elliot,Brian Palmer,Ronalg Mendes Costa d' Assunção Carvalho,Lien-Fen Tseng,Cheng-Sheng Lee,Kun-Hsien Tsai,B. Greenhouse,Hsiao-Han Chang

Published 2025 in Communications Medicine

ABSTRACT

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. 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. 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. 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. Chen et al. conduct a genome-wide analysis of malaria parasites collected over 7 years from Sao Tome and Principe. The study reveals low genetic diversity, clonal turnover, importation, and limited recombination. There is a need for targeted strategies such as stopping importation and improving detection to halt transmission to achieve total elimination. Malaria cases in Sao Tome and Principe rose again around 2012 and have stayed low since, but the disease has not been eliminated. To address this, it is important to understand how malaria continues to spread. By analyzing genetic data of malaria parasites, we found that imported cases may bring new genetic types of the parasite into the population. This can lead to further local transmission and changes in the parasite population, such as the spread of drug resistance. Our findings show the importance of reducing imported cases and stopping their spread, as well as focusing on areas with relatively high transmission and using reactive case detection during the later stages of malaria control programs.

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