Spatio-temporal trends of molecularly diagnosed clinical malaria cases in The Gambia, captured across sentinel surveillance health facilities.

Malaria transmission is becoming more heterogeneous across sub-Saharan Africa (sSA), with the drive to pre-elimination by low-transmission countries like The Gambia under the threat of local or imported artemisinin and partner drug resistance. This calls for enhanced surveillance of parasite evolution and transmission as interventions are intensified. The Genomic Surveillance of Malaria (GSM) in West Africa project has established two hubs in The Gambia and Ghana to support malaria elimination efforts. Towards the Gambia GSM hub, we report trends in clinical malaria cases at GSM sentinel sites confirmed by molecular diagnosis over a 4-year period (2019 to 2022). A total of 10,052 study participants from 383 villages were recruited at 23 health facilities in the six regions of the country. Across the years, PCR-positive proportions of suspected malaria ranged from 15.2% - 63.2% in the Central River Region; 20.3% - 43.6% in the Lower River Region; 9.4% - 39.9% in the North Bank Region; 31.1% - 73% in the Upper River Region; 29.2% - 71.4% in the Western Region 1; and 33.5% - 58.3% in the Western Region 2. While there was a decline in clinical cases in the historically higher transmission upper river region, more cases were detected in the semi-urban western sentinel sites. Approximately 12.9% of infections detected by PCR were missed by RDT across all regions and there was an upward trend of single-strain P. falciparum infections over the study period. Integrating these molecular approaches in routine surveillance systems of the National Malaria Control Program could provide high-resolution data for prevalence stratification and customized interventions for targeted local malaria elimination strategies. What is already known on this topicFinescale geospatial and temporal studies for malaria heterogeneity are not common. A PubMed search (March 18, 2024) using the terms "malaria molecular surveillance" and "clinical malaria" and "transmission" and either "spatial analysis" or "temporal analysis" yielded 27 results of which only three specifically reported spatial and/or temporal analysis of clinical malaria infections. Of these three studies, one did not use molecular methods for diagnosis, and another was a pre-print that reported the prevalence of Plasmodium species in a demographic health survey. Thus, only one study reported the use of a molecular detection method for micro geographical analysis of clinical and subclinical malaria infections from three villages to identify infection clusters and their potential relationship to malaria transmission. What this study addsSpatial and temporal mapping of clinical malaria cases in an area of low, heterogeneous transmission (like The Gambia) reveals areas of persistent malaria infections that could be potential candidates for targeted interventions. While the recommended malaria rapid diagnostic tests (RDTs) are generally suitable for clinical confirmation before treatment, they are not reliable in detecting low-grade infections which are more prevalent in low-transmission settings. Furthermore, results from RDTs are limited in providing levels of parasitemia, complexity of infections, and their distribution in demographic groups required for the accurate definition of layers of country stratification and intervention strategies. This study provides a high-resolution nationwide basis for translational malaria molecular surveillance in The Gambia using clinical malaria cases. How this study might affect research, practice or policyAs endemic settings near malaria elimination, intervention strategies should be adapted with approaches such as reactive case detection and foci investigation from an index case needed to further drive down local transmission and prevent reintroduction of imported cases. These approaches will benefit from integrating novel technological methods including molecular diagnosis and genetic fingerprinting. With molecular surveillance of clinical cases in low-transmission settings, low-grade infections can be detected towards more effective targeting of interventions, particularly where false negative RDTs become more prevalent. The results presented here suggest that more sensitive diagnostics will increase the resolution of malaria prevalence estimates to support elimination.