Making Data Map Worthy - Enhancing Routine Malaria Data to Support Surveillance and Mapping of Plasmodium Falciparum Antimalarial Resistance in a Pre-Elimination Sub-Saharan African Setting: A Molecular and Spatiotemporal Epidemiology Study

Abstract

Background: Independent emergence and spread of artemisinin-resistant Plasmodium falciparum malaria has recently been confirmed in Africa, with molecular markers associated with artemisinin resistance increasingly detected. Surveillance to promptly detect and effectively respond to antimalarial resistance is generally suboptimal in Africa, especially in low transmission settings where therapeutic efficacy studies are often not feasible due to recruitment challenges, yet these communities may be at higher risk of antimalarial resistance. Methods: From March 2018 to February 2020, we conducted a sequential mixed-methods study to evaluate the feasibility of the near-real-time linkage of individual patient antimalarial resistance profiles with their case notifications and treatment response reports and map these to fine scales in Nkomazi sub-district, Mpumalanga, a pre-elimination area in South Africa.Results: Plasmodium falciparum molecular marker resistance profiles were linked to 55.1% (2636/4787) of notified malaria cases, 85% (2240/2636) of which were mapped to healthcare facility, ward and locality levels. Over time, linkage of individual malaria case demographic and molecular data increased to 75.1%. No artemisinin resistance validated/associated kelch13 mutations were detected in the 2385 PCR positive samples. Almost all 2812 samples assessed for lumefantrine susceptibility carried the wildtype mdr86ASN and crt76LYS alleles, potentially associated with decreased lumefantrine susceptibility. Conclusion: Routine near-real-time mapping of molecular markers associated with antimalarial drug resistance on a fine spatial scale provides a rapid and efficient early warning system for emerging resistance. The lessons learnt here could inform scale-up to provincial, national and regional malaria elimination programmes, and may be relevant for other antimicrobial resistance surveillance.