WHO prohibits the use of Artemisia annua

“…your statement about solving the malaria problems with herbal medicines is frightening”. U d’ Alessandro, expert of the ITG-Antwerp, in email dated 25 Jan 2015. The large family of Artemisia plants have been used as herbal medicine for millenniums in all regions of the world. It is now well established that other plants of the Artemisia family have an antimalarial effect, such as Artemisia absinthium, Artemisia sieberi, Artemisia maritima or Artemisia afra. This is not a surprise because Chinese scientist Shengua (1095) and Li Shisten (1593) had found that Artemisia apiacea which does not contain any artemisinin had better antimalaria properties than Artemisia annua. Artemisia absinthium and Artemisia herba alba herbs have been used successfully for many years by the French army in Algeria as a remedy against malaria. To allow soldiers to swallow this bitter potion, they added some alcohol to it. The drink absinthe was born. An addicted smart corporal, after repatriation, had the idea to launch the production of absinthe in France; and had amazing success. The winemaker lobby could only look unfavorably at the loss of big market shares. What to do? To declare that one of the components of absinth was toxic: the thujone. It has been rehabilitated today. Like anything consumed with moderation, even wine, it can be beneficial to health. After the Vietnam war the merits of Artemisia annua were forgotten, All this only had a folkloric interest because the West had an effective and cheap drug: chloroquine. However, by 1990 severe resistances against this drug became apparent. Some scientists took the stick of the pilgrim and came back from China with the information concerning this herb, but were not able to convince the WHO of its benefits. It is only ten years later that a pharmaceutical company signed an agreement with the Chinese. But to launch on the market a cheap drug, accessible to every horticulturalist/farmer, didn’t interest either party. In 1979, the Chinese had published an Artemisia annua analysis and found artemisinin, a peroxide which when used in-vitro was super-efficient against Plasmodium. A kind of trade agreement was concluded for the use of this molecule by the Western Companies. But it turned out that artemisinin was not soluble in water, it was hardly bioavailable and it started its own metabolism of elimination by using the cytochrome CYP 3A4 leading to a half lifetime of 3 hours in the blood. Soon came the phenomena of resistance for the monotherapy to artemisinin, and in a way more pronounced, against the liposoluble and hydrosoluble derivatives: artemether and artesunate. What to do? Somebody had the idea to bring out from cellars and attics old molecules as amodiaquine, mefloquine, the unsalable lumefantrine, some of them already forbidden in several countries. The trick is called ACT (Artemisinin Combined Therapy). The first in-vitro and in-vivo trials were very promising, regularly reaching a cure rate approaching 90% after PCR correction. The reinfection rate remained high. The problems were rather industrial and commercial. How to quickly find enough artemisinin for the huge demand and how to invade the market with a pill which had a production cost at least ten times higher. To conquer the market, the producers of ACT artemether-lumefantrine made an agreement with the WHO which, since 2001, gradually introduced this remedy as a requirement and as a front-line treatment in many African countries. Around 2007 the artesunate-amodiaquine mixture was also authorized and placed on the market with the support of MMV and MSF. For their efforts it was agreed that these humanitarian organizations were entitled to 3% on the sales of pharmaceutical companies for these medicines. The second major problem was the availability of raw material. The Chinese possessed for a long time a monopoly of the plant and the artemisinin molecule. But the variety they used only contained 0.2% of artemisinin, which requires huge agricultural areas. The Swiss laboratory Mediplant developed a hybrid which contained 1.4%. It was used by pharmaceutical companies to create their own production areas in Africa and in several countries. The problem of this hybrid was that it did not give seeds and the African farmers had to buy them every year, even if they were not able to sell the harvest of the last year. A state of dependence which led to many bankruptcies. Especially since the Chinese had lowered the prices at the same time. Also, the price of the ACT was too high for African families, even though pharmaceutical companies claimed they sold it at a low price and bragged in media of their charitable approach. Anyway, according to 2008 WHO report, the penetration rate of the ACT in Africa did not exceed the 3% target and the 2014 report suggests a very dubious claim and an increase in penetration. Meanwhile, many European and African associations became acquainted with the benefits of the plant and knew of its efficiency against malaria. The clinical trials conducted in early 2000s in several countries had convincing results. A wave of panic was felt in upper floors of pharmaceutical companies backed by Geneva. The WHO published in 2004 on its website an unsigned document, not referenced, not signed, undated, as a violent attack against the use of Artemisia annua as herbal tea against malaria, with statements which to-day have all proven to be erroneous http://www.who.int/medicines/publications/traditional/ArtemisiaStatement.pdf. WHO Position Statement on Effectiveness of Non-tablet Forms of Artemisia annua L against Malaria Since the World Health Organization (WHO) recommended the use of artemisinbased combination therapies for malaria in 2001, a number of other forms of Artemisia annua L for use as anti-malaria "remedies" have appeared, including tea bags made from the plant's leaves. WHO does not recommend the oral use of any form of artemisinin other than capsules and tablets. The recommended strength of artemisinin is 250mg capsules or tablets according to the International Pharmacopeia, published by WHO. Artemisinin content in raw materials is quite low, approaching 1% even in high-yield raw materials. For this reason it is virtually impossible for a tea bag to contain the amount of substance required to cure malaria. Due to the instability of artemisinin in raw materials of Artemisia annua L, the leaves need to be stored in cool conditions — preferably below 20°C. Most malaria endemic countries have warm climates and people generally lack access to refrigeration, so it is difficult for patients to keep artemisinin-containing tea bags under 20°C in their homes. Artemisinin contained in raw materials of Artemisia annua L is unstable when heated. Boiling water to make tea may cause it to lose any anti-malarial properties it may have. The pamphlet coming from an organization considered independent and disinterested was to persuade not only the African governments, but also ministers of the European cooperation. Five centuries ago the science was banished on the riverbanks of the Tiber, now blockages are made on the riverbanks of the Scheldt and the Rhone. In both cases the arguments remain lame and dogmatic. First of all, WHO claimed that the dose delivered by the tea was lower than the dose prescribed and necessary for the cure: 250 mg of artemisinin. It would thus be necessary to swallow 1 kg of grass in one form or another to reach that dose. But this dose of 250 mg of artemisinin dates from the time when the low bioavailability of artemisinin became evident, which required a very high dose. In 1994 doses of 2x500 mg a day were used, but these reached hepatotoxic and neurotoxic levels. The argument of the dose of 250mg has since been dismantled by the works of Pr. Pamela Weathers at the Worcester Polytechnic Institute. Consumed as a tea or rather as a powder of ground leaves, the bioavailability is at least ten times superior to that of the pure artemisinin. It was wrongly claimed that the artemisinin contained in dried leaves is not stable. The work of at least five laboratories have shown that leaves stored in a dry and ventilated place remain stable for 3 years, and even ten years. It is the artemisinin and its derivatives in tablets that under tropical conditions are very unstable, sometimes not exceeding a half-life of a few weeks as shown by the laboratory of Parasitology of the Hospital Bichat-Claude Bernard. This partially explains that the majority of ACT pills sold in Africa have very low contents of artemisinin, not to mention counterfeit product unscrupulously put on the market. And then there is the overwhelming argument of the resistance generated by the herbal tea. Low concentrations of artemisinin would let some parasites survive and become more resistant than others, which from generation to generation would make the fight impossible by patented pharmaceutical products. But the opposite occurred. Massive doses of artemisinin can lead to a phenomenon of adaptation in parasites or viruses and can generate new super resistant strains. It is what was noticed on the pyrethroids of mosquito nets ITNs. The 2014 WHO Malaria Report laid out billions spent on ITNs and ACTs but has to recognize that malaria is increasing in the most afflicted countries as Benin, Burundi, RDC, Cameroon, Senegal, Togo, Uganda, Tchad, Guinea, Sierra Leone … For the ACTs, ten years ago, uncontrollable resistances were noticed in countries of Southeast Asia and for 5 years now in about ten African countries, a fact difficult for the WHO to recognize. In this context, the team of professor Weathers’ quoted above was able to show that the Artemisia powder consumption in the form of tablets or capsules never led to resistances in long duration trials, and even lowered pre-existing resistances. In fact since two thousand years and among thousands of people using the herbal tea against malaria, the phenomena of resistance has never been established. WHO even had the arrogance to say that herbal tea is a monotherapy. The Artemisia annua plant contains at least 20 active ingredients which act by synergy or addition. All the healing plants are combination therapies unlike the pharmaceutical molecules used in monotherapy. With clinical trials we learnt that it is better to use the grass in the form of “totum” dried powder, capsules, tablets or as an additions in food, because this guarantees that the lipophilic substances are bioavailable. It was also insinuated that Artemisia annua could contain toxic substances, which led in Belgium to a law in 1998 prohibiting the Artemisia annua herbal tea. Many attempts have been made in recent years to overturn this hypothesis. We could not find any acute or chronic toxic effects even at higher doses, but rather beneficial effects on the renal and hepatic functions and on hyperglycemia and high blood pressure. Artemisia annua is moreover authorized in many countries, to mention only a few; Germany, Luxembourg, The Gambia, Uganda, Austria, Romania, Poland, South Africa, Egypt, the United States, New Zealand, Senegal, Morocco, Madagascar, Palestine, Australia, Iran, China, and Ethiopia. IFBV- BELHERB is a Belgian-Luxembourgish association of physicians and scientists whose main objective is the development of medicinal herbs in tropical countries. It works now closely with French and German doctors. Originally the parent NGO IFBV had mostly humanitarian projects of school construction and other infrastructures, but it soon realized that the main problem of African countries were tropical and dysenteric diseases: 25000 children die daily from it and the impact on education and economy is enormous. IFBV-BELHERB knew that the battle could be won only by a more rigorous scientific and medical approach. Over the years, it was able to build a network and partnership with African and South American universities: 8 in Africa and 4 in South America. Clinical trials in a dozen of countries, most of them published in the scientific literature, show that the Artemisia annua herbal tea has a healing rate ˃ 95%. Due to the regular intake of tea we also noticed in several countries a prophylactic effect. In villages where the plant is used, malaria is plummeting. The University of Makerere with the Ministry of Health in Uganda even developed and marketed the product ARTAVOL whose prophylactic effects have been clearly demonstrated and documented in the scientific literature. While artemisinin and its derivatives have only a curative effect and destabilize the immune In our works with African Universities we have learned that in many countries of South and East African, a local plant, Artemisia afra was widely used against malaria. For four years we have been studying this plant. It seems that it is equivalent or even superior to Artemisia annua in vitro and in vivo trials, or in anecdotical reports from Tanzania. It is the plant which contains the highest concentration of the flavone luteolin, a molecule with demonstrated antiplasmodial, anti-inflammatory and anticancer properties. Our current projects aim to replace Artemisia annua by Artemisia afra, be it only to break the vicious circle of conflicts with the WHO-Bigpharma business that protects artemisinin like a cash cow. Research is also based on laboratory work. Thorough analysis of plants in the National Laboratory of the Health at Luxembourg and at the University des Montagnes in Cameroon, determination of the antiplasmodial components in Brussels and Louvain. But it is specially the test of inhibition of beta-hematin (or haemozoin) by various herbs and substances such as carried out at the University of Liege and Al Quds University that drive us forward. It must be remembered that inhibition of hemozoin is the main mechanism of action of quinine. Thanks to these works we were able to see that certain additions such as baking soda increased the potential therapeutic effect of the aqueous infusion. IFBV-BELHERB until now wanted to limit its works and projects to the use of Artemisia against malaria. In other words, we wanted to establish our projects on most solid scientific and medical bases. However, it is a very complex problem. Today, for example, there are still five academic theories in discussion to explain the mechanism of action of artemisinin. But in the meantime, many of our partners have attacked other diseases using Artemisia annua. We have well documented results on the effectiveness of herbal tea against leishmaniosis in Antioquia University in Colombia, against cancer at the University of Belgrade, against Trypanosoma cruzi at the University of Cumana in Venezuela, against diarrhea and bilharzia in Senegal and RDC, against tuberculosis and Buruli ulcer in RDC, AIDS at the University of Leiden, typhoid fever in Burundi. But, as admitted by a state employee of a Ministry of the Gulf of Benin, “It is beautiful, but if you succeed, who will pay for our trips to the international conferences”. Who better than A. Sanner in his thesis at the University of Nancy, summarizes what has been said in this article. “During the import of commercial medicine, the government benefits from two sources of income: import tax and registration fee. When a Natural Medicine drug is produced locally, the government benefits at most from a low registration fee. The implementation of thousands of micro projects of Artemisia culture distributed on their territory thus deprives them of substantial tax revenues. The example of the customs duties perceived on mosquito nets and insecticides illustrates the aberration of certain state practices. In 2000, in Swaziland and in Sudan, the price of a soaked mosquito net was respectively 45 and 30 US dollars because of governmental taxes superior to 50% of the purchase price. The collusion of the WHO and the pharmaceutical industry does not allow the necessary independence of such a body to estimate the medical or medicinal alternatives in the fight against malaria. WHO identifies administrative costs of 3% of the sale price of every Coartem treatment and have established, with the producing laboratory Novartis, a situation of monopoly by granting them the only qualification in the market for fixed dose ACTs, until very recently. The WHO plays the role of promoter and intermediary between the multinationals and the developing countries. In this situation, how could the WHO show any interest for medicinal plants or lead research in this field while receiving so much money from the industry by introducing opposite arguments in its favor? In the absence of rigorous clinical trials to validate the use of Artemisia annua infusions and with regard to the risks moved forward by his detractors, are we entitled to skip over this therapeutic alternative when we measure sometimes the extreme conditions of isolation of victims of malaria in the dry regions of Africa and the rain forest of Amazonia? Malaria occurs in the poorest countries with access difficulties to health structures situated tens and even hundreds of kilometers from villages. Drugs are too expensive or counterfeit. In its declarations, the West supports the right of people to self-determination. The hypocrisy consists in dispossessing them with the help of so called humanitarian international organizations”