Phytochemical synergy in artemisia annua herbal tea against malaria: a systematic review of its efficacy and safety in the context of emerging Pfkelch13 resistance
Abstract
Background: Emerging Plasmodium falciparum resistance to artemisinin derivatives, mediated principally by mutations in the Pfkelch13 propeller domain, is reshaping the antimalarial therapeutic landscape across sub-Saharan Africa and the Greater Mekong subregion. Concurrently, whole-plant Artemisia annua herbal tea has re-emerged in malaria-endemic settings, prompting renewed scrutiny of its phytochemical matrix and its clinical performance relative to artemisinin-based combination therapy. The present systematic review synthesises the contemporary evidence on the efficacy and safety of Artemisia annua herbal tea against P. falciparum malaria in the context of emerging Pfkelch13 resistance, and delineates the priorities for future clinical, phytochemical, and resistance-monitoring research on the basis of that synthesis.
Methods: A PRISMA-2020-compliant systematic review was conducted across six databases for the period January 2000 to December 2025. Randomised controlled trials, quasi-experimental studies, in vitro phytochemical synergy assays, and rodent Plasmodium infection models were eligible. Two reviewers screened, extracted, and quality-rated the studies independently (Cohen's κ =0.83) using RoB 2.0, Newcastle-Ottawa, and the RITAM stacking criteria. A qualitative narrative synthesis with GRADE-style confidence rating across twelve outcomes was performed.
Results: Thirty studies were retained. Mechanistically, whole-plant A. annua delivers over forty co-extracted…
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