The slow erosion of artemisinin's effectiveness against malaria may represent one of the most consequential drug-resistance crises of the coming decade — not merely a clinical inconvenience, but a mechanism that actively amplifies transmission at the population level. Understanding why resistance matters beyond individual treatment failure is essential for anyone tracking global infectious disease trajectories.
This PRISMA 2020-compliant systematic review, registered with PROSPERO and drawing from nearly 900,000 initial records across PubMed, Embase, and Web of Science, ultimately distilled 22 studies published between 2011 and 2025. The central finding is stark: artemisinin resistance, predominantly driven by kelch13 gene mutations, has reached a prevalence of 5%–47% in Southeast Asia and is now confirmed to be emerging in Sub-Saharan Africa and South Asia — regions bearing the world's greatest malaria burden. Critically, resistant parasite strains don't merely fail treatment; they prolong active infection duration and increase gametocyte carriage, the mosquito-transmissible reproductive form of the parasite, thereby mechanistically enhancing onward spread. Treatment failure rates rise from a baseline of roughly 5% to between 15% and 20% in resistant contexts.
What elevates this review beyond routine surveillance reporting is its framing of resistance as a transmission amplifier, not solely a therapeutic problem. This aligns with emerging modeling literature suggesting that even modest increases in parasite survival time can disproportionately boost community-level transmission intensity. The kelch13 mutation landscape is well-characterized in the Greater Mekong Subregion, but its foothold in Africa — where Plasmodium falciparum prevalence is vastly higher — could render current artemisinin-based combination therapy (ACT) protocols obsolete at scale. Key limitations include the inability to conduct meta-analysis due to study heterogeneity, the reliance on only 22 studies from a massive initial pool, and observational design dominance. This review is confirmatory of known trends but provides a structured synthesis that sharpens the urgency around next-generation antimalarial pipeline development.