Artemisia annua and Artemisia afra tea infusions vs. artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial

Abstract

Background and objective: Prior small-scale clinical trials showed that Artemisia annua and Artemisia afra infusions, decoctions, capsules, or tablets were low cost, easy to use, and efficient in curing malaria infections. In a larger-scale trial in Kalima district, Democratic Republic of Congo, we aimed to show A. annua and/or A. afra infusions were superior or at least equivalent to artesunate-amodiaquine (ASAQ) against malaria.

Methods: A double blind, randomized clinical trial with 957 malaria-infected patients had two treatment arms: 472 patients for ASAQ and 471 for Artemisia (248 A. annua, 223 A. afra) remained at end of the trial. ASAQ-treated patients were treated per manufacturer posology, and Artemisia-treated patients received 1 l/d of dry leaf/twig infusions for 7 d; both arms had 28 d follow-up. Parasitemia and gametocytes were measured microscopically with results statistically compared among arms for age and gender.

Results: Artemisinin content of A. afra was negligible, but therapeutic responses of patients were similar to A. annua-treated patients; trophozoites cleared after 24 h, but took up to 14 d to clear in ASAQ-treated patients. D28 cure rates defined as absence of parasitemia were for pediatrics 82, 91, and 50% for A. afra, A. annua and ASAQ; while for adults cure rates were 91, 100, and 30%, respectively. Fever clearance took 48 h for ASAQ, but 24 h for Artemisia. From D14-28 no Artemisia-treated patients had microscopically detectable gametocytes, while 10 ASAQ-treated patients remained gametocyte carriers at D28. More females than males were gametocyte carriers in the ASAQ arm but were unaffected in the Artemisia arms. Hemoglobin remained constant at 11 g/dl for A. afra after D1, while for A. annua and ASAQ it decreased to 9-9.5 g/dl. Only 5.0% of Artemisia-treated patients reported adverse effects, vs. 42.8% for ASAQ.

Conclusion: A. annua and A. afra infusions are polytherapies with better outcomes than ASAQ against malaria. In contrast to ASAQ, both Artemisias appeared to break the cycle of malaria by eliminating gametocytes. This study merits further investigation for possible inclusion of Artemisia tea infusions as an alternative for fighting and eradicating malaria.

Keywords: ACT; ASAQ; Artemisinin; Clinical trial; Malaria; Tea infusion.

Fig. 1.

Trial design.

Fig. 2.

Average fever progression among the three treatment arms. Top, graphical representation. Bottom, Kaplan–Meier; survival time of fever started when a patient was included in the study (D0). Patients were followed until D28. For patients withdrawing from the study before D28 or still having fever until D28, survival time is said to be censored. The survival probability was calculated using the Kaplan–Meier method. The censored rates of A. annua, A. afra, and ASAQ are 0.0%, 10.3%, and 26.7%, respectively, with p-value of log-rank still near to zero and statistically significant.

Fig. 3.

Average parasitemia progression among the three treatment arms. Top, graphical representation. Bottom, Kaplan–Meier; survival time of parasites started when a patient was included in the study (D0). Patients were followed until D28. For patients withdrawing from the study before D28 or still having parasites until D28, survival time is said to be censored. The censored survival rates of A. annua, A. afra, and ASAQ are 3.6%, 11.2%, and 65.7%, respectively.

Fig. 4.

Microscopically determined proportion of patients with gametocytes (carriers) throughout the trial period.

Fig. 5.

Hemoglobin levels during the first four days of treatment.