African Journal of Traditional, Complementary and Alternative Medicines African Ethnomedicines Network ISSN: 0189-6016 Vol. 4, Num. 1, 2007, pp. 121-123

African Journal of Traditional, Complimentary and Alternative Medicines,, Vol.4, No. 1, 2007, pg. 121-123

LETTER TO THE EDITOR

ARTEMISIA ANNUA AS A HERBAL TEA FOR MALARIA

¹Dr Merlin Willcox (Secretary), Dr. Jacques Falquet²,Dr. Jorge F.S. Ferreira ³, ⁴ Dr Ben Gilbert,⁵ Dr. Elisabeth Hsu,⁶ Dr Pedro Melillo de Magalhães,⁷ Prof. J. Plaizier-Vercammen, ⁸Prof V.P. Sharma,⁹ Dr Colin W. Wright, ¹⁰ Prof Wan Yaode,

¹36 Hare Close, Buckingham MK18 7EW, UK. merlinwillcox@doctors.org.uk ,
²Scientific Coordinator, Antenna Technologies, Geneva, Switzerland. jfalquet@antenna.ch
³US Department of Agriculture -Agricultural Research Service, 1224 Airport Road, Beaver, West Virginia 25813, USA jorge.ferreira@ars.usda.gov
⁴Instituto de Technologia em Fármacos, Far-Manguinhos, Fundação Oswaldo Cruz, Rua Sizenando Nabuco 100, Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil. gilbert@far.fiocruz.br
⁵Institute of Social and Cultural Anthropology, University of Oxford, Oxford, UK. elisabeth.hsu@anthropology.oxford.ac.uk
⁶Coordinator, Divisão de Agrotecnologia, CPQBA-UNICAMP, Campinas, Brazil. pedro@cpqba.unicamp.br
⁷Vrije Universiteit Brussel, Farmaceutische Technologie & Fysische Farmacie, Laarbeeklaan 103, B-1090 Brussel, Belgium. e-mail: jplaizie@vub.ac.be
⁸ Meghnad Saha Distinguished Fellow, Centre for Rural Development and Technology, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India. vinodpsharma@gmail.com
⁹Reader in Pharmacognosy, The School of Pharmacy, University of Bradford, West Yorks BD7 1DP, U.K. C.W.Wright@Bradford.ac.uk
¹⁰Sichuan Institute of Chinese Materia Medica, Chengdu Sichuan, China. annie223@163.com

Code Number: tc07001

Dear Sir,

Jansen (2006) writes that "the herbal tea approach to artemisinin as a therapy for malaria is totally misleading and should be forgotten as soon as possible."

We believe that this statement is totally misleading and should be forgotten as soon as possible, for the following reasons.

1. The extraction method used was flawed. Boiling water will destroy most of the artemisinin, instead of extracting it, but artemisinin is better extracted in hot water (85-90° C) or milk (because of the fat content). Traditional Chinese texts suggest that the fresh juice of the plant was used (obtained by maceration and squeezing in cool water), and at much greater concentrations (Hsu, 2006). Artemisinin is stable in acid, so will survive passage through the stomach. More research is needed, using a variety of different preparations of Artemisia annua.
2. Dry Artemisia annua leaves do not lose their artemisinin fast. In proper storage conditions, the artemisinin is present in almost whole amounts even after one year of storage. Where is Dr Jansen's scientific evidence that artemisia is susceptible to mould? Artemisinin is stored in glandular trichomes of leaves and flowers of A. annua. The essential oils are also stored there. Thus, fungi do not have a pleasant environment to grow in. If the plant is stored dry, the artemisinin should be there from one season to the next.
3. No one is suggesting that artemisinin is the only active ingredient in Artemisia annua. Jansen acknowledges that the effectiveness of the tea is partly due to other ingredients, as the dose of artemisinin is too low to account for the observed effect. This is confirmed by in vivo experiments in mice which showed that A. annua infusion reduces parasitaemia by 50% at day 4, compared to the equivalent dose of pure artemisinin, which was not significantly more effective than placebo (Plaizier-Vercammen, unpublished). The presence of other active ingredients suggests that A. annua is a natural artemisinin combination therapy (Willcox et al, 2004). These other ingredients also merit further research, to see whether their presence hinders the development of parasite resistance compared to pure artemisinin.
4. In the same experiments, A. annua infusion was less effective than the full dose of artemisinin (which was tenfold higher), suggesting that the infusion was not strong enough. The doses used by Jansen (2006), Mueller et al (2004) and Räth et al (2004) are purely arbitrary, and lower than those used in traditional chinese medicine (Hsu, 2006). Nine grams per litre is a very weak infusion: most medicinal infusions are made at the much higher strength of 50g of dried herb (or 100g of fresh herb) per litre of water (Green, 2000). If the preparations tested are insufficiently effective, the dose needs to be increased. Clinical studies in China have shown that a dose of 72-125g of Artemisia annua per day for three days was highly effective (Yao-de, unpublished). Experience to date and the literature suggest that A. annua is safe and non-toxic, though safety in pregnancy has not been established. Its LD50 is 162.5 g/kg (Chang & But, 1986). Research is needed on tenfold stronger infusions (to reach 50g of herb per litre of water) to compare their efficacy and safety with pure artemisinin at the same dose.
5. As the above statements make clear, further research is needed on Artemisia annua teas, to try to improve on the results obtained thus far. Important questions to address include: can the efficacy of A. annua tea be increased so that it becomes an acceptable complement to ACTs? How can we ensure that patients receive an adequate dose? Can A. annua tea be safely used without accelerating the appearance of resistant strains of Plasmodium? It is not possible to answer these questions with a single experiment on a single preparation of A. annua tea.
6. While "ACTs for all"would be the ideal strategy, it is most impractical for poor and remote communities, politically unstable areas, and people who dislike the use of modern medicine. There are almost five billion febrile episodes resembling malaria every year (Breman et al, 2004), most of which need to be treated as malaria, since most areas do not have adequate diagnostic facilities. Even at the cost of $1 per course of treatment (which is half the current price of ACTs) this would cost almost $5 billion per year, which is ten times the currently available budget for malaria. Even if this money miraculously appeared, the health infrastructure is lacking in most of the areas worst affected by malaria, making it impossible to distribute the drugs to those who most need them. For example, in the Brazilian Amazon, patients commonly have to travel for two days before reaching a modern health facility. Although recrudescence can occur after treatment with Artemisia annua tea, is this not preferable to patients dying before they reach the health facility? Why not recommend the tea as a "first aid"measure to keep the patient alive while they travel to the health centre?

Yours sincerely,

RITAM Artemisia annua Task Force ( www.gifts-ritam.org)

References

1. Breman, J. G., Alilio, M. S. and Mills, A. (2004). Conquering the intolerable burden of malaria: what's new, what's needed: a summary. Am J Trop Med Hyg 71 (suppl 2): 1-15.
2. Chang, H. M., But PPH (1986). Pharmacology and applications of Chinese Materia Medica; Vol 1. Singapore: World Scientific Publishing.
3. Green J (2000). The Herbal Medicine-Maker's Handbook. Berkeley, California: The Crossing Press.
4. Hsu E (2006). The history of qing hao in the Chinese materia medica. Trans Roy Soc Trop Med Hyg 100: 505-508.
5. Jansen, F. H. (2006). The herbal tea approach for artemisinin as a therapy for malaria? Trans. R. Soc. Med. Hyg. 100: 285-286.
6. Mueller, M.S., Runyambo, N.,Wagner, I., Borrmann, S., Dietz, K. and Heide, L. (2004. Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria. Trans. R. Soc. Trop. Med. Hyg. 98:318,321.
7. Räth, K., Taxis, K., Walz, G., Gleiter, C.H., Li, S.-M. and Heide, L. (2004). Pharmacokinetic study of artemisinin after oral intake of a traditional preparation of Artemisia annua L. (annual wormwood). Am. J. Trop. Med. Hyg. 70: 128-132.
8. Willcox ML, Bodeker G, Bourdy G et. al. (2004). Artemisia annua as a traditional herbal antimalarial. In: Willcox ML, Bodeker G. and Rasoanaivo P (2004). Traditional Medicinal Plants and Malaria. Boca Raton: CRC Press.