Understanding the global rise of artemisinin resistance: Insights from over 100,000 <i>Plasmodium falciparum</i> samples.

Abstract

Artemisinin partial resistance (ART-R) in <i>Plasmodium falciparum</i> is a major challenge to malaria control globally. Over the last two decades, ART-R has spread widely across Southeast Asia, undermining public health strategies and hindering elimination. As of 2024, ART-R has now emerged in East Africa, with the potential to dramatically impact current efforts to control malaria in the region. Mitigating its spread requires detailed genomic surveillance of point mutations in the <i>kelch13</i> gene, the primary known determinant of artemisinin resistance. Although extensive surveillance data on these markers is available, it is distributed across many literature studies and open databases. In this review, we aggregate spatiotemporal data for 112,933 <i>P. falciparum</i> samples collected between 1980 and 2023 into a single resource, providing the most comprehensive overview of <i>kelch13</i> markers to date. We outline the history and current status of these mutations globally, with particular focus on their emergence in Southeast Asia and East/Northeast Africa. Concerningly, we find the recent increases in ART-R in Africa mirror patterns observed in Southeast Asia 10-15 years ago. We examine factors that may influence its spread, including fitness costs, treatment strategies, and local epidemiological dynamics, before discussing potential scenarios for how resistance may spread in Africa in coming years. This review provides a comprehensive account of how the situation of ART-R has unfolded globally so far, highlighting insights for researchers and public health bodies which aim to reduce its negative effects.