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Should Artemisia annua (wormwood) tea be used as a prophylactic in endemic countries?

December 18, 2012 - 14:56 -- Bart G.J. Knols

This expert blog was contributed by Dr. Merlin Willcox, Honorary Secretary of the Research Initiative on Traditional Antimalarial Methods (RITAM), in response to the outcome of a poll on MalariaWorld and recent contributions regarding the use of Artemisia tea as a remedy for malaria.

As a scientist and medical doctor, I am interested in herbal medicines for malaria. No one can deny that they have been the source of the two most important and effective families of antimalarial drugs. Furthermore many people still rely on various herbal remedies for treating uncomplicated malaria. Much of my own research has aimed to investigate these objectively and to find the most effective remedies.
 
Artemisia annua is a very interesting plant and is the source of the most powerful antimalarial drug ever discovered, artemisinin. There are a few clinical trials which even show that it can be used as an “emergency, first-aid” treatment for malaria in semi-immune adults. However there are no published clinical trials which prove effect on the prevention of malaria, and no published clinical trials which demonstrate effectiveness in young children...

Some of the claims being made recently on the pages of MalariaWorld are questionable. For example: “A "vaccine" against malaria from Africa: ARTAVOL” claims that  “The product has been released after clinical and community trials over 3 years which have demonstrated that if taken regularly during one year it renders a person immune against malaria.”
 
No such trials have been published. It is highly unlikely that taking ANYTHING for one year would render a person “immune” against malaria. Even the best vaccines have so far failed this test. The only thing which does seem to give some level of immunity is continued low-level exposure to malaria parasites. The claim is misleading and might distract people from proven interventions such as the use of insecticide-treated mosquito nets.
 
There are some interesting comments for and against the poll on this subject. I doubt whether use of Artemisia annua is a significant contributor to drug resistance, because the plant does contain other antimalarial compounds, and is not widely used in south-east Asia, where resistance has in fact occurred. However, it is misleading to say that “no resistance has been observed so far”. How do you define resistance? The trial of Mueller et al (2004) showed that many patients experienced a recrudescence of parasites after a treatment with Artemisia annua tea. This may not be resistance per se, but it does indicate that the tea is not as miraculous as some people claim. 
 
The reason for being cautious about this approach, at least in my case, is not motivated by pharmaceutical companies’ greed. I have no conflicts of interest and no involvement with any pharmaceutical companies. My only interest, as a medical doctor, is to find the best treatment for patients, to prevent needless deaths from malaria, particularly in African children. 
 
The fact of the matter is that so far, no published clinical trials have demonstrated that Artemisia annua tea is effective in the prevention or treatment of malaria in children. A few small trials have shown some effectiveness in the treatment of malaria in semi-immune adults. However young children do not have the same levels of immunity so the treatment may not be so effective in them. If there really is no other treatment available, it is probably better than nothing as a “first aid” option while looking for more effective ACTs. Although it is true that there are fake ACTs, the real ACTs are the most effective antimalarials currently available. It could be considered unethical to promote Artemisia teas at the expense of ACTs in young children.
 
Most of the studies quoted are poorly designed and have fundamental flaws in their design. For example if there is no control group, how can you know that the effect is real? If patients are only followed for 2 days instead of 28 days, how can you be sure that the treatment really prevented malaria? Variations in parasite counts occur commonly even without treatment. 
 
It is time for us to work together on high-quality scientific research, to find and develop the most cost-effective treatments and prophylactics for malaria. I am convinced that there are good treatments and prophylactics waiting to be discovered and developed from the plant kingdom. Unfortunately it is difficult to find funding for this sort of research. The lack of evidence tends to polarise people into two camps – those “FOR” who enthusiastically promote herbal products with minimal evidence; and those “AGAINST” who denigrate herbs as being “unscientific” or “quackery”. It would be better to take a middle path, using high-quality scientific evidence and research to guide us to develop truly effective and safe antimalarial treatments and prophylactics. Meanwhile, when giving guidance to patients and NGOs, we would be wise to stick to what has actually been proven to work in high-quality clinical trials. 
 
Reference:
Mueller MS, Runyambo N, Wagner I, Borrmann S, Dietz K, 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(5):318-321.
 
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Comments

Submitted by Ogwang Patrick (not verified) on

Dear All,

It is interesting reading the debate on malaria, Artemisia annua and ARTAVOL.

First I want to say I live in uganda in Africa where malaria is a problem and I used to suffer from malaria four times a year. I want to put it clear that in 2006 I investigated use of Artemisia tea for malaria prevention in two large farm groups, one in KIGO tea farm in western Uganda and another in Wagagai flower farm in central Uganda near Entebbe airport and found that the Artemisia tea reduced fever cases among the users by over 80% but this was not controlled clinical trial.

So in 2008 I submitted a proposal to the government of Uganda to fund us to investigate the effectiveness and safety of Artemisia tea in prevention of malaria using Randomised control trial method. We conducted the study for 12 months and proved that Artemisia tea taken regularly does not just reduce fever cases by more than 80% but actually brings malaria cases to 0% by the eigth month of intake.

This work has been published in the British Journal of Pharmaceutical Research and Tropical Journal of Pharmaceutical Research and a PhD thesis of Makerere University, the top university in Sub Saharan Africa.

We established that the mode of action is not dependent on Artemisinin but rather flavonoids and polysaccharides and it is through induction of immune system majorly. We then proceeded to develop a product devoid of artemisinin but rich in flavonids and polysaccharides and fortied it with two other plant extracts for use as tea for prevention of malaria and it is called ARTAVOL for which a patent has been filed.

ARTAVOL is available in Pharmacies and supermarkets in Kampala and many people are now using it, including sickle cell children in Mulago hospital, pharmacist, doctors, and government officials. Dr Merlin Willcox has met me many times and he knows the truth about Artemisia tea and he knows that I and Prof Obua Celestino and Prof Ogwal-Okeng Jasper of Makerere University conducted this study and this study was done in Adults.

I agree with him in children we do not know the effect of Artemisia tea because no one has done a study of prophylaxis in children. We are now planning testing of Artemisia annua in combination with some of the local plants for malaria cure. if we can develop cure also then we can have total solution for malaria for us in Africa and who suffer from malaria. I appreciate the effort by those who live in non malaria areas and who try to talk about malaria but I request that they should rubbish Africa effort to solve African problem. Thank you

I am grateful to Patrick for pointing out his important research, and I apologise for not quoting this in the blog. I was aware of his first paper which is an observational study:
http://www.sciencedomain.org/abstract.php?iid=71&id=14&aid=151
This showed that there were 16.7% fewer cases of laboratory confirmed malaria in adult farm workers who were choosing to drink Artemisia annua tea once a week. This is an interesting preliminary finding but no firm conclusions can be drawn because there may have been confounding factors.

At the time of writing the blog I was not aware of his second paper, but have now found this:
http://www.tjpr.org/vol11_no3/2012_11_3_14.pdf

This is a well-conducted randomised placebo-controlled trial of once weekly Artemisia annua tea for the prevention of malaria in adult farm workers. It shows a protective efficacy of 37.5% in those who were drinking the tea once a week over a 9-month period. This is the best evidence I have seen to date of Artemisia annua tea reducing the incidence of malaria.

However it is to be emphasised that both of these trials were of Artemisia annua tea, not of "ARTAVOL". They do not show that a person is "rendered immune against malaria". And as Patrick points out, no children were included.

On the basis of this one study (and in medicine we prefer to see several studies before being certain that something works), one can conclude that semi-immune adults may experience fewer episodes of malaria if they drink Artemisia annua tea once a week. One cannot however extrapolate to non-immune adults (i.e. travellers or those in non-endemic areas) or children. Neither can one extrapolate to different herbal preparations. It would be good to repeat similar studies in other areas to see if this effect is replicated.

I congratulate Patrick on his excellent research and wish him every success with his future planned trials.

Submitted by Tom Chapman (not verified) on

Whilst I love the simplicity of being able to grow Artemisia annua and make a brew of tea to use as a prophylactic as a Pharmacist and a manufacturer I think this could be dangerous because only the artesunate in the plant is soluble and the artemether would be left behind so I have a problem with both the quality of this sort of extract and the amount of active being extracted. Another problem is that no one has done any studies to find out what the minimum dose which does not cause tolerance is (it could be very low) so for the moment I would only reccomend "standardised" products for treatment and not for prophylaxis, sorry to damp anyone's enthusiasm.

Submitted by Dana Dalrymple on

The blog by Dr. Willcox is very much to be welcomed. Teas largely fall outside the realm or purview of malariologists. He is uniquely qualified to provide a larger perspective.

In the course of preparing my book, I ventured into this area in Section 1.1.4., "Traditional medications and science" (pp. 5-13) and in Annex 4, "Artemisinin: Phytochemical Extraction" (pp. 184-185). The latter notes that "the plant itself is a rich source of phytochemical diversity: monoterpenes, sesquiterenes, flavenoids and polyacetylene epoxides" and that some of these "might also play play a useful role in enhancing the medicinal effect of artemisinin."

Based on these brief explorations I would endorse virtually everything he says, and have only a few observations.

* In para. 6, he states "I doubt whether the use of Artemisia annua is a significant contributor to drug resistance, because the plant itself is a rich source of phytochemical diversity...(and) might also play a useful role in enhancing the medicinal effect of artemisinin, though the mechanism involved...is uncertain." Hence the prospect of "good treatments and prophylactics waiting to be discovered and developed from the plant kingdom"," while a topic of some efforts, has proved elusive so far and may prove to be even more so. Moreover, as he notes, finding funding for this sort of research is difficult.

Later, in para. 8, he suggests that "It could be considered unethical to promote Artemisia teas at the expense of ACTs in young children." This is a good point that I hadn't thought of.

One issue that neither of us really got into, though I briefly mentioned it (p. 11), is what to do about situations where much of the rural population is so remote from either the public or private sectors that they essentially beyond the reach of pharmaceuticals. For them, as one individual from the DR Congo pointed out to me years ago, the only option may be teas.

More generally, the distinctions between preventative and curative drugs might be more fully delineated. Quinine has been used for both. Artemisinin and ACTs have not: they are almost purely curative by nature and cost. Quinine, however, seems to have survived on both fronts, probably aided by the fact that some of their side effects are repugnant/undesirable and limit adoption/use; also their plant base renders them expensive as well. The main limitations of ACTs are their cost and their probability that their overuse will lead to the lessening of resistance.

Submitted by Irene Teis on

- Artemisia does not contain artesunate or artemether. These are industrial derivatives and they are now causing severe resistance problems in several countries.
- Artemisin is present in the artemisia annua plant alongside several other molecules with antimalarial properties. The plant is used since 2000 years and has never caused any resistance.
- Other Artemisia plants like apiacea, absinthium, afra, sieberi, maritima do not contain artemisinin and are used in many countries as antimalarials
- As far as I know the prophylactic ARTAVOL does not contain any artemisinin, nor artesunate or artemether.
Irene Teis

Pierre Lutgen's picture
Submitted by Pierre Lutgen on

For Patrick Ogwang: information received from European partner

" Patrick,I want to share with you our experience which to a large extent is in agreement with yours.

Our association is involved with the efficiency of Artemisia annua, more in the fight against cancer than malaria. Over the years e came to the conclusion that artemisenin can't be the main reason for the positive results booked with Artemisia annua tea. Other research groups even found that artemisinin or artesunate in monotherapy may provoke resistance.

Two facts astonished the people who use the Artemisia annua herb against cancer

- The tea we initially had purchased did not work against cancer in vivo. We thought it would have been better than the tea from Luxembourg because it contains ten times more artemisinin (1.2 % vs 0.15 %), but it didn't work.

- The tea from the small stems and twigs from the Luxembourg plants worked just as well against cancer as the tea from the leaves, although stems contain even less artemisenin. Is some other active component present in the stems responsible for that?

Cancer patients however, keep on drinking Artemisia annua tea year after year and so far the results of the Luxembourg plants are the only good ones, without any side effects. We have plenty of tea here with high artemisenin content, but it stays where it is: unused.

Our organisation is also active in Lubumbashi-Katanga with artemisia annua plantations.

Patrick, we may want to line up and profit from your results over there. I already spread the word about ARTAVOL in Lubumbashi.

Bart G.J. Knols's picture
Submitted by Bart G.J. Knols on

 

(The comment below was submitted by Irene Teis (by email)):
 
Question for Dr Merlin Willcox concerning the statement hereafter made on his MalariaWorld expert blog:
 
“ My only interest, as a medical doctor, is to find the best treatment for patients, to prevent needless deaths from malaria, particularly in African children.  The fact of the matter is that so far, no published clinical trials have demonstrated that Artemisia annua tea is effective in the prevention or treatment of malaria in children.....Children do not have the same levels of immunity so the treatment may not be so effective in them.”
 
This statement is somewhat in contradiction with your own very positive assessment in a peer reviewed paper :” Overall the number of children treated was at least 250...They reported that all the children treated had recovered completely. (Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria, Merlin L Willcox   et al., in Malaria Journal 2011, 10:84).
 
Your partner Anamed claims on his homepage that many thousands of patients have been treated with Artemisia annua tea at a cure rate of > 90%. No mention is made that the infusion was less efficient for children.
 
The ACT artemether-lumefantrine  is approved by WHO, including children and their approval is based on several clinical trials involving children.
 
I am afraid that your caveat published with your credentials as medical doctor on a blog accessible to thousands of people might frighten medical staff in Africa and prevent the use of Artemisia annua by poor families in remote villages for their children.
 
Irene Teis