<i>Artemisia annua</i>: A New Version of a Traditional Tea under Randomized, Controlled Clinical Trial for the Treatment of Malaria

Abstract

Introduction: The traditional antimalarial tea Artemisia annua, indicated for centuries in China to treat fevers, is again arousing interest for the treatment of malaria due to improvements attained in the plant composition by a few Institutions throughout the world, including the State University of Campinas (UNICAMP), Brazil, increasing its principal component by more than 100 times as from standard varieties, giving 1% in artemisinin and an expressive biomass yield such as 2 tons of dried leaves/hectare. Clinical trials carried out with this material in African countries have proven its therapeutic potential for a new generation of Artemisia tea in the treatment of falciparum malaria. In addition to artemisinin, recent studies have identified and quantified other compounds present in the crude extract and characterized their contributions to the anti-malarial efficacy, including their action against chloroquine-resistant strains. The majority of the clinical trials carried out with Artemisia tea in African countries have shown that the control of the parasitaemia is efficient in the initial treatment period, but few trials have followed the patients up to the 28th day. This first clinical trial carried out in Brazil with the A. annua infusion, after toxicological trials that defined the safety of this form of medication. Methods: The therapeutic efficacy of the tea was measured in patients with falciparum malaria over 28 days, comparing it with the current first-line treatment namely artemether-lumefantrine (Coartem?). The trial was carried out in controlled groups according to official protocol approved by the National Ethics in Research Committee (CONEP: 77/ 2011) and a rigorous control of the 17 patients with non-serious cases of falciparum malaria, recruited in the following three municipalities of the State of Para, Brazil: Tucurui, Goianesia do Para and Anajas. The tea group received the infusion prepared in the proportion of 1.25 g of dry leaves of the variety CPQBA with 1% artemisinin for 250 mL of just boiled water, taken every 6 hours for 7 days, giving a total of approximately 175 mg of artemisinin, whilst the artemether-lumefantrine (Coartem?) group received a total of 525 mg of artemisinin equivalent to artemether. Results: The parasitaemia by the tea treatment became negative in the first days, even though it was administered with a dose that was one third of the recommended dose of artemisinin. However, as in the case artemisinin or artesunate monotherapies, 57.1% of the patients treated with the A. annua tea presented type I resistance, with a return of the parasitaemia around the 14th or 21st day. The other patients in the tea group showed type II/III resistance without manifestation of any serious signs or symptoms. In these cases, according to the protocol, the patients were redirected for treatment with artemether-lumefantrin (Coartem?) with subsequent negativity of the parisitaemia. Discussion: The fact that the efficacy of the tea with 1/3 of the dose of artemisinin was similar to that of the full dose of this medication infers that other compounds present in the crude extract, probably flavonoids, had contributed to the negativity of the parasitaemia at the start of the treatment. Considering that the positive control group, where the compound derived from artemisinin (artemether) was associated with another antimalarial agent (lumefantrine), presented excellent efficacy throughout the entire control of the cure, future trials with the A. annua tea should use the same strategy of association with another antimalarial agent, preferably from A. annua itself, in order to extend its therapeutic action during the whole control period. The Artemisia annua tea in the form standardized and used in this research, should not substitute the most efficient treatment, but could be considered as an emergency therapeutic resource in the first hours of symptoms as a function of its availability, anti-inflammatory action and lack of side effects. Other regimes and standardizations deserve investigation, mainly those with a high content of arteannuin B, as occurs in the initial cultivation phase.