Slowing the spread of treatment failure to artemisinin-based combination therapies in Uganda.

The continuing spread of partially artemisinin-resistant Plasmodium falciparum in Africa is a health challenge that requires urgent attention. The World Health Organization has recommended multiple first-line therapies (MFT) as a response strategy. Implementing a response is critical for Uganda where four artemisinin resistance mutations are at local allele frequencies >0.20 and partner-drug efficacy may be at risk. Using a Uganda-calibrated individual-based mathematical model of P. falciparum transmission and evolution, we evaluate 53 public-sector deployment strategies for artemisinin-based combination therapies and report projected reductions in drug-resistance associated treatment failure from 2025 to 2031. Changing first-line therapy from artemether-lumefantrine (AL) to artesunate-amodiaquine (ASAQ) is projected to reduce treatment failures by 34.7% to 38.3% (90% range) while a first-line policy change to dihydroartemisinin-piperaquine (DHA-PPQ) is projected to reduce treatment failures by 10.0% to 12.9%. Optimal MFT deployments and cycling approaches balance their treatment distribution to higher ASAQ use and lower DHA-PPQ use, with projected treatment failure reduction at ~36% when compared to status quo AL use. Deployment of the triple therapy artemether-lumefantrine-amodiaquine is projected to reduce treatment failures by ~42% if enacted immediately. Increased adoption of and coverage with ASAQ is projected to play a large near-term role in reducing malaria treatment failure counts in Uganda.