review · Infectious Diseases of Poverty
A systematic review evaluated the efficacy and safety of Artemisia annua whole-plant herbal tea against malaria, particularly in the context of emerging parasite drug resistance linked to Pfkelch13 mutations. In laboratory and animal models, the whole-plant matrix displayed enhanced potency compared to purified artemisinin and delayed the emergence of resistance threefold. Clinical trials confirmed rapid initial parasite clearance within seventy-two hours, accompanied by predominantly mild side effects such as bitter taste and gastrointestinal discomfort. However, sustained day-twenty-eight cure rates for the herbal tea fell drastically short of the standard ninety-five percent threshold achieved by artemisinin-based combination therapies. Consequently, the herbal tea cannot serve as a direct replacement for standard combination treatments. Critical safety data also remain lacking for young children, pregnant women, and patients with organ comorbidities, highlighting the necessity for targeted clinical trials and molecular surveillance.
Rising resistance to front-line artemisinin-based medicines threatens malaria control across Africa and Asia. Understanding whether whole-plant herbal formulations can overcome resistant strains helps public health authorities evaluate traditional remedies. While the tea shows biological mechanisms that slow resistance, its inability to ensure lasting cure means it cannot safely replace proven combination therapies without risking recurrent infection.
The findings indicate that whole-plant Artemisia annua preparations are not viable as standalone pharmaceutical alternatives to artemisinin-based combination therapy due to high treatment failure rates by day twenty-eight. Any future commercialisation or therapeutic use would require formulating the extract as a complementary treatment within standardised combination regimens. Development remains at an early applied research stage, requiring rigorous pharmacokinetic standardisation, safety testing in vulnerable populations, and stratified clinical efficacy trials before clinical adoption.
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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: values were 3-5 × lower than those of equivalent-concentration purified artemisinin on 3D7, chloroquine-resistant, and multidrug-resistant strains. In Pfkelch13-mutant rodent P. falciparum lines, stable resistance to whole-plant therapy emerged three times more slowly than to equivalent-dose purified dihydroartemisinin. Clinically, retained randomised trials demonstrated rapid initial parasite clearance within 72 h-Mueller day-7 cure 74% vs 91% (quinine); Blanke day-7 cure 7/10 vs 7/9 and day-28 cure 1/9 (11.1%); Magalhães first-day parasitaemia-negative at ~ 175 mg cumulative artemisinin- but day-28 parasitological cure rates of A. annua monotherapy fell consistently below the 95.5-98.6% artemisinin-based combination therapy (ACT) benchmark band wherever directly reported [Blanke 1/9 (11.1%) vs sulfadoxine-pyrimethamine 3/8 (37.5%); Magalhães 0/7 sustained cure]. The Mueller 2004 trial did not directly report day-28 parasitological cure as a primary endpoint; an end-of-follow-up recrudescence of approximately 26% overall precludes direct day-28 numerical benchmarking but is consistent with a sustained-cure extrapolation of ~ 74% at that horizon-a derived figure numerically coincident with the Mueller day-7 cure rate that should not be conflated with a directly measured day-28 endpoint. Adverse events were predominantly mild (bitter taste, transient GI discomfort), with no serious events recorded in any retained study; safety data for children under five, pregnant or lactating women, and patients with hepatic or renal co-morbidity remain critically insufficient. CONCLUSIONS: Whole-plant A. annua herbal tea achieves reproducible early parasitological clearance and preserves the multi-target pharmacological substrate whose pre-clinical resistance-modulation profile (three-fold slower resistance emergence in Pfkelch13-mutant murine lines) is biologically coherent with a Pfkelch13-modulating effect, although this effect has not yet been clinically reproduced in Pfkelch13-endemic African settings. The ≥ 84-percentage-point day-28 cure-rate gap between directly-reported A. annua monotherapy and the African ACT benchmark band frames the present-day clinical use of A. annua infusion as a complementary or adjourning intervention rather than a replacement for ACT. This positioning is preserved while Pfkelch13-stratified randomised trials, vulnerable-population safety studies, and population-scale molecular resistance surveillance are designed and executed.
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DOI: 10.1186/s40249-026-01486-x
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