WHO | Drug resistance could set back malaria control success (2/25/2009)

[Giuseppe]

WHO | Drug resistance could set back malaria control success

Drug resistance could set back malaria control success

US$ 22.5 million grant from Gates Foundation to contain malaria parasites resistant to artemisinin


25 FEBRUARY 2009 | GENEVA --

WHO today said that the emergence of parasites resistant to artemisinin at the Thai-Cambodia border could seriously undermine the success of the global malaria control efforts.


Surveillance systems and research studies supported by WHO to monitor antimalarial drug efficacy in countries are providing new evidence that parasites resistant to artemisinin have emerged along the border between Cambodia and Thailand. If local people, who walk for miles every day to clear forests, were infected with a drug-resistant form of malaria, it could set back recent successes to control the disease.

Huge strides have been made in the past 10 years to reduce the burden of malaria, one of the world's major killer diseases. Strong malaria control programmes have helped to lower infection rates in several countries. The recent shift from failing drugs to the highly effective artemisinin-based combination therapies (ACTs) has been a breakthrough. Appropriate treatment with ACTs succeeds in more than 90% of cases. But malaria drug resistance now emerging along the Thai-Cambodia border threatens these gains.

With a US$ 22.5 million grant from the Bill & Melinda Gates Foundation, WHO will endeavour to contain artemisinin-resistant malaria parasites before they spread. WHO will work in collaboration with several key partners including the National Center for Parasitology, Entomology and Malaria Control of the Cambodian Ministry of Health, Bureau of Vector-Borne Disease of the Thai Ministry of Public Health, Faculty of Tropical Medicine of Mahidol University Bangkok, Institut Pasteur Cambodia, Mahidol Oxford Tropical Medicine Research Unit, Bangkok and the Malaria Consortium.

"If we do not put a stop to the drug-resistant malaria situation that has been documented in the Thai-Cambodia border, it could spread rapidly to neighbouring countries and threaten our efforts to control this deadly disease," said Dr Hiroki Nakatani, Assistant Director-General of WHO.

Resistance along the Thai-Cambodia border started with chloroquine, followed by resistance to sulfadoxine-pyrimethamine and mefloquine, drugs used in malaria control several years ago.

Malaria poses a risk to half of the world's population and more than one million people die of the disease each year. The malaria map, or the area where it is prevalent, has been reduced considerably over the past 50 years, but the disease has defied elimination in areas of intense transmission.

Obstacles to malaria control include drug resistance in the parasite that causes the disease, as well as resistance of the vector mosquito to insecticides, environmental factors and counterfeit medicines. The likelihood of drug resistance is increased with the use of single-drug therapies for malaria, especially monotherapies of artemisinin and its derivatives. Monotherapy fosters resistance because it is easier for the parasite to adapt and eventually overcome the obstacles presented by a single drug than a combination of drugs delivered together. This makes it crucial for monotherapies to be removed from the market. WHO's treatment policy is to treat all cases of uncomplicated falciparum malaria with artemisinin combination therapy (ACTs).

"We know that malaria can be treated and prevented,? said Dr Regina Rabinovich, Director of Infectious Diseases Development at the Bill & Melinda Gates Foundation, ?and if we lose the key treatment available at this time, it's like living in a house with a half a roof.?

The grant will be used to meet the following key objectives:

* Eliminate artemisinin-tolerant parasites by detecting all malaria cases in target areas and ensuring effective treatment;

* Reduce exposure of the parasites to artemisinin to limit emergence of resistance;

* Prevent transmission of artemisinin-tolerant malaria parasites through mosquito control and personal protection;

* Limit the spread of artemisinin-tolerant malaria parasites by mobile populations;

* Support the containment and elimination of artemisinin-tolerant parasites through comprehensive behaviour change, communication, community mobilization and advocacy;

* Undertake basic and operational research to fill knowledge gaps and ensure that strategies applied are evidence-based; and

* Provide effective management, surveillance and coordination to enable a rapid and high-quality implementation of the strategy.

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<cite cite="http://www.who.int/mediacentre/news/releases/2009/malaria_drug_resistance_20090225/en/index.html">WHO | Drug resistance could set back malaria control success</cite>

 

[nomadic wench]

Re: WHO | Drug resistance could set back malaria control success (2/25/2009)

Many of today's drugs originate from plants that have been used as traditional remedies.

The "modern" way is to isolate one active component and slightly change the molecular structure so that it can be patented. WHO strongly discourages people using plants rather than pills that have patented ingredients... very irresponsible and unscientific! In fact a lot of effort goes into trying to get rid of the need for plant raw materials because it pushes up costs....let's produce this vital ingredient using bacteria sludge instead.


What we tend to forget is that a medicinal plant doesn't have just one active component...there are many and they usually work in synergy.

An example is artemisia annua, the source of artemisinin used in drugs like Coartem to treat malaria. Coartem contains one semi-synthetic derivative of artemisinin (artesunate) and a drug that is very similar to mefloquine. There is widespread resistance to mefloquine. This combination will stop resistance to artemisinin developing according to the WHO.

Artemisia annua has been used for about 1000 years by the Chinese to treat malaria with no signs resistance. The natural plant contains a whole bunch of anti-malarial compounds (seven AFAIK) which work in synergy together. An NGO called Anamed has shown that simple herbal teas cure falciparum malaria very effectively in Africa.

http://www.anamed.net/English_Home/anamed_artemisia_programme/anamed_artemisia_programme.html

However, the WHO says we shouldn't use natural artemisia any more as it will cause resistance to the drugs THEY recommend.

Since 2004 the Bill Gates foundation has been donating a lot of money towards the synthetic production of artemisinin so they can make cheaper pills.

That's five years and millions of deaths while waiting for production to start.The fact that there will probably be widespread resistance to artemisinin by the time production gets online doesn't seem to have occurred to anyone till now.

Wouldn't it have been better for Gates to donate all that money to people like Anamed while we are waiting for a vaccine? Think of the advantages of people being able to grow their own cures in their back yards for free. No trying to get to a hospital (which could be days away) to get pills. No problems of corrupt officials and logistics. No problems of counterfeit drugs. Giving the people concerned some control over whether they live or die.

People tried and Gates Foundation ignored them.

 

[nomadic wench]

Re: WHO | Drug resistance could set back malaria control success (2/25/2009)

C&P from the Anamed link above which addresses WHO objections to using artemsia teas.

Artemisia annua Tea - a revolution in the history of tropical medicine

The golden opportunity that, because of economic and bureaucratic interests, the world is likely to miss

Updated: 15th August 2006

Each year 300 million people suffer from malaria, and between 1 and 3 million people die of malaria. The rediscovery of the plant Artemisia annua is therefore a matter of joy in the world of tropical medicine. Artemisinin, extracted from the plant, acts 10 to 100 times more quickly than all other known malaria medicines (1).

The key question is, is it necessary to first extract the artemisinin from the dried leaves with an organic solvent, and then to manufacture tablets, or is it possible more simply to grow artemisia and to make tea from the dried leaves?

Let?s think: A reduction in the death-rate due to malaria in Africa of only 20% would result in an economic benefit equal to the entire development aid Africa receives (20 billion USD per year) (2). Or, if we could show that artemisia could heal 80% of malaria cases, then this Natural Medicine, that costs almost nothing to produce, could bring a financial benefit equal to 4 times the entire development aid budget for Africa!

In reviewing artemisia, the German television channel RTZ announced ?Malaria: Victory in sight!? and the ?Sueddeutsche Zeitung? (a newspaper for southern Germany) described it as ?The plant that could save Africa? (3). We say, quite simply, yes, victory is in sight, not in the sense of the destruction of the enemy, but in the sense of co-existence. Humanity will never eradicate malaria, and malaria need no longer threaten to eradicate mankind! Our vision is that malaria can be treated, that it can be treated for the next thousands of years, and that also the poorest people may have malaria treatment for thousands of years. That is the golden opportunity.

For this purpose we have proposed detailed treatment guidelines (4). We recommend using dried and powdered artemisia leaves as a tea for internal use, and in the form of an aqueous extract as an enema for unconscious patients. For those cases in which artemisia alone is not enough, we describe how artemisia may be combined with old, patent-free and therefore cheap, synthetic anti-malarials, particularly for example with AIDS patients or children under 5 years old. Using these malaria treatments, based on artemisia tea, an African country can build an effective front against the threatening advance of malaria, without either suffering ever increasing drug prices or holding out the begging cap to Bill Gates.

There are many who disagree with our recommendations. We take their comments seriously. We answer our critics as follows:

1. ?You have not examined sufficient numbers of malaria patients to claim that artemisia tea is effective?. During recent years, anamed partners have collected a wealth of experience. For example, Ralph Wiegand in Arba Minch, Ethiopia, Maike Ettling in Musoma, Tanzania. Both have treated over 1000 malaria patients with a success rate of between 80 and 100% (5).

2. ?The healing rate with the whole plant extract is too low?. In the scientific literature, three Chinese studies showed up to 100% effectiveness when powdered artemisia leaves were administered directly as powder, or mixed with oil, or extracted with alcohol (1). These are all procedures that even the most basic and most remote African clinic could follow.

3. ?The tea does not kill every last plasmodium?. The most important thing for the African is not that every last plasmodium is destroyed, but the freedom from symptoms. Many Africans always have plasmodia in their blood, which provide a protection against new infections. The study of Dr Mueller (6) in the University of T?bingen showed that 7 days after the start of treatment with artemisia tea, 77% of the patients no longer had an elevated temperature, in 88% the tiredness disappeared, and in 92% muscle pain and nausea disappeared. In fact, the experience of anamed groups in many African countries is that the cure rate, and the rate of loss of symptoms, is much higher than this. If at this stage the patient has not recovered, at least he should now have enough strength to walk to the nearest clinic for a full medical examination to determine what his disease really is. (In the Congo that could easily be 100 km (7), or in Amazonia a 3 day journey by boat (8)).

4. ?The artemisinin level in the blood is too low. To treat malaria properly, patients would have to drink 20 litres of tea every day?. The University of T?bingen (6) has shown that after drinking 1 litre of artemisia tea each day for 7 days, antimalarial effective blood levels were reached. Volunteers that drank tea made from 9 grams of dried artemisia leaves had a peak plasma level of 240 nanograms of artemisinin per ml. This is 26 times higher than the minimum artemisinin concentration required for growth inhibition of Plasmodium falciparumin vitro (14). This university, however, does not recommend artemisia tea for the treatment of malaria because, within four weeks of being treated many patients in the clinical study suffered a new malaria attack. This may, however, be due to new infections. We would like to point out that artemisinin has a very short half-life, only 1? hours, in comparison with, for example, Fansidar, which has a half-life of up to 3 weeks! For this reason we insist that the tea is drunk for 7 days, even sometimes 12 days, and that everything possible be done to prevent a new infection.

It is also important to remember that the artemisinin in artemisia tea has the additional effect of strengthening the immune system (1). Many patients, including those who suffer from quite different diseases such as typhoid fever, AIDS, rheumatism or bronchitis, tell us that, after drinking the tea, they feel new strength.

5. ?Worldwide the greatest fear is that the malaria parasite might develop resistance to artemisinin, and this danger will increase through the use of artemisia tea. That would render the last weapon in the fight against malaria useless?. We also share this concern, but we have absolutely no fear that by using artemisia tea we are increasing this risk. The tea has been used in China for 2000 years, without resistance developing. Now the pharma industry has become involved. Drug companies have isolated artemisinin and produced tablets of this single antimalarial component, and in less than 20 years the first signs of resistance have been observed (9). If artemisinin were to become ineffective, then, sorry, it is industry and not natural herbal therapy that would be to blame.

Throughout history there is in fact no record of any parasite becoming resistant to a whole plant extract. For example, there is resistance to synthetically made chloroquine, but tea made from the bark of the cinchona tree is just as effective today as it has been for hundreds of years.

6. ?With modern artemisinin based drugs we have an absolutely reliable therapy for malaria - why use a primitive tea?? In our opinion, the opposite is true! Firstly, a tea made of home-grown artemisia can be trusted much more than tablets bought in a pharmacy in a tropical country. Artemisinin or its derivates (e.g. artesunate, dihydro-artemisinin) worldwide are expensive and not available in sufficient quantities. This has proved to be the ideal situation for the illegal production of counterfeit medicines. (See ?Manslaughter by Fake Artesunate?, 15). That means that these firms add just enough of the declared ingredients, maybe as low as 1%, so that the tablets pass the quality checks. This is tantamount to murder. It also gives the malaria plasmodia every opportunity to develop resistance. In contrast, the characteristic taste of artemisia tea is such that no fakes have ever yet been reported.

Secondly, today, even the majority of Artemisinin Combination Therapy (ACT) drugs (i.e. isolated artemisinin combined with another antimalarial drug) sold in Vietnam and Cambodia are fakes (12)!

Thirdly, in ACT preparations, we have two different antimalarial drugs that have different half-lifetimes in the blood. The ACT drug is usually taken during 3 days. The first component is a artemisinin derivate that always has a half-life of one to two hours. This means, on the evening of the third day, there is no more artemisinin in the blood of the patient. The second drug however is lumefantrine with a half-life of 5 days, or even mefloquin with a half-life of 3 weeks! This means, if a patient takes the artemisinin derivate + lumefantrine, on day 4 to day 9 he has only lumefantrine in his blood. If he takes the combination artemisinin derivate plus mefloquin, on day 4 to day 25 he has only mefloquin in his blood, and sub-therapeutic doses of it many weeks more. This means that if a person is bitten by a mosquito during this later "window" period, (and many patients are bitten by mosquitoes every day) the plasmodium encounters only a monotherapy. The plasmodium has, therefore, enough time to develop resistance to this second product. We quote, ?reports of treatment failure emerged soon after artemether - lumefantrine was introduced in Zanzibar, with genetic evidence for selection of lumefantrine resistant parasites? (16).

It is, therefore, absurd to demand that we do not use artemisia tea to treat malaria so as not to endanger the effectiveness of the tablets: the artemisia tea is a far more sustainable solution!

7. ?Compared with the use of a single isolated substance, the effect of a whole extract cannot be accurately quantified and therefore gives too many uncertainties?. We should learn from history. For decades scientists have condemned valerian tincture because no single, effective substance could be isolated. The conflict was resolved by the acknowledgement that valerian tincture is only effective because of the synergy of all the various constituents, and to isolate one ingredient makes no sense. Many independent scientists confirm that this is also true for artemisia tea (13).

8. ?Artemisia tea is a monotherapy and should therefore not be used.? Artemisia tea is certainly no monotherapy. Antimalarial substances in the plant include artemetin, casticin, chrysoplenetin, chrysosplenol-D and cirsilineol (1). The effectiveness of the tea depends upon the synergistic effect of 29 sesquiterpenes, 36 flavonoids und a variety of essential oils (1). The effect of artemisia tea depends only to a low extent on the artemisinin content. It has even been demonstrated several times that extracts from the tea containing no artemisinin at all are still effective against malaria. There are in fact varieties of artemisia that contain no artemisinin at all, and still have some anti-malarial activity, e.g. A. absinthium, abrotanum and afra.

9. ?After 6 months the dried leaves have lost most of their artemisinin content and are then useless.? We have shown that the artemisinin content of a properly dried sample of artemisia tea remains stable for three years. The research scientist Dr. Pedro Mellilo of the University of Campinas in Brazil has even shown that, in a properly stored sample the artemisinin content actually increases with time, as a result of the conversion of the precursors (9). We in anamed take care to ensure that our African partners dry and store their artemisia tea properly.

10. ?anamed should recommend that people in Africa grow artemisia only for sale to industry.? There is today a worldwide shortage of artemisinin. The price of isolated artemisinin has exploded, because farms cannot produce enough artemisia leaves. It is in our view irresponsible, out of the available harvest, only to extract the artemisinin and to throw the rest of the plant away. The precursor of artemisinin, artemisinin acid, can be present in the plant in a concentration eight times higher than artemisinin itself (1), but in extracting artemisinin alone this is all thrown away. Many more people could be treated if these same plants were used for artemisia tea. African farmers can sell their dried tea as a medicine for around 20 Euro per kilo to hospitals but for less than half a Euro to the pharmaceutical industry (our experience in Tanzania).

11. ?In comparison to tablets, it is too difficult to measure the correct dosage of tea.? In our anamed publications we have clearly defined the minimum quality of ?Artemisia annua anamed? tea. Artemisia tea can be given in dosages that are just as precise as those for tablets. Anamed Tanzania fills artemisia tea manually into tea-bags. Anamed South Africa uses a machine to fill tea bags or capsules, and now produces 3 tonnes a year (10)

Our work would be made very much easier, if:

1. African governments were more interested in the health of their people and the economic development of the country, rather than government income. When a commercial drug is imported, the government receives income from two sources; the import tax and the registration fee. When a Natural Medicine is produced locally, the government can only benefit, at most, from a low registration fee. For example, governments have much more income from imported Voltaren for rheumatism treatment, than from locally produced chilli ointment. This is equally true for the import of Coartem to treat malaria, as compared with if local clinics grow and use artemisia tea.

2. The WHO were to free itself from the tentacles of industry, by having its administration costs paid out of public funds and not by courtesy of the pharmaceutical industry. The world urgently needs an independent WHO, not a WIO (World Industry organization)! The WHO would appear to be so poor that it receives a fee of one million USD, just for acting as an intermediary for the supply of Coartem to Kenya, according to the Kenyan newspaper Daily Nation (11). How could the WHO possibly have any interest in healing plants or conduct any research in this area, when for putting counter-arguments in their favour they receive so much money from industry? And, worldwide, how can doctors remain neutral and advise their patients with a clear conscience, when they are legally obliged to give recommendations that arise out of such vested interests?

3. University research worldwide were to be paid out of public funds, so that it became more problem orientated than product orientated in the interests of the pharma industry.

In summary, artemisia tea is ready for the market, not from big industry but in a way that thousands of small projects can take on. Anamed does not patent anything. Only this way can tropical countries develop their own production capability. A European military organisation offered to finance our research, on condition that we did not publish the results. We declined this generous offer!

Anamed offers humanitarian organisations worldwide: 1) freedom to grow appropriate varieties of artemisia without the payment of any royalties, 2) freedom to use artemisia tea without the payment of royalties and 3) access, completely free of charge, to the instructions for its use for the treatment of malaria and other diseases (available on the internet www.anamed.net).

On the other hand, as is clear from our series of books ?Natural Medicine in the Tropics?, anamed is not fixed on one single plant. We encourage all countries to examine further locally available antimalarial plants, for use alone or in combination with Artemisia annua. RITAM has recorded over 1000 medicinal plants that are used for malaria. We look forward to the results of research that is being conducted in many tropical countries into their locally available medicinal plants. Some of these may in the future be used in a combination with Artemisia annua, which would be an example of ?herbal combination therapy? (HCT). For the few cases in which artemisia tea alone is not effective, such an HCT could be the answer.

Acknowledgement: We thank all those who have contributed to us being able to reach this position, particularly scientists, doctors and thousands of patients.

Anamed partners look after 650 artemisia fields in 75 countries.

Dr Hans-Martin Hirt, Dr Keith Lindsey, anamed (Action for Natural Medicine), Schafweide 77, 71364 Winnenden, Germany Web: www.anamed.net

Copyright: anamed. This means that humanitarian organisations are free to photocopy this text and to use it for educational purposes. The text may not be used to support any claims of industry.

References:

1. Willcox, Merlin et al (2004) "Artemisia annua as a Traditional Herbal Antimalarial" in "Traditional Medicinal Plants and Malaria", CRC Press Washington, pp43-59.
2. WHO, (2000) "Economic costs of Malaria....", Press Release WHO /28, 25 April 2000.
3. S?ddeutsche Zeitung, 21.12.2004, "Ein Kraut gegen den Killer" page 3.
4. see www.anamed.net.
5. Wiegand, Ralph, Arba Minch, Ethiopia, and Ettling, Maike, Musoma, Tanzania, personal communications, April 2006.
6. Mueller, Markus et al, Transactions of the Royal of Tropical Medicine and Hygiene (2004), 98, pp318-321.
7. Hirt, Hans-Martin: Report of the visit to Bokungu-Ikela, D. R. Congo, 12/2003.
8. Melillo, Pedro, University of Campinas, Letter to RITAM , 11.03.2006.
9. Afonso, A et al, (2006). ?Malaria parasites can develop stable resistance to Artemisinin...? Antimicrobial Agents and Chemotherapy 50: pp480-489 cited in "The world of Artemisia", Royal Tropical Institute, Netherlands, 2006.
10. Example: Mirmed tea 35 g in 14 tea bags, Emseni Farming, (mail(at)ksb.org.za) and Malarlife capsules (www.malarlife.dfl.org.za).
11. Daily Nation, Newspaper in Kenya, April 14, 2005:"Factions differ over drug tender" "But pharmaceutical sources accuse WHO of pushing Coartem because as a procurement agency for the country it will be paid a three per cent agent fee by the buying country. Kenya will use a total of $ 34 million a year for purchasing the drug and therefore WHO will get approximately $1 million."
12. Gathura, Gatonye, (2005), "Counterfeits hit new malaria drugs", The Daily Nation newspaper, Kenya, 17 Nov. 2005.
13. Duke, James R, (2005), Chemical and Engineering News, May 2, Vol. 83, No 18, pp4-5. (James Duke is the author of the famous Duke Phytochemical and Ethnobotanical Database.)
14. Heide, Lutz, (2006), ?Artemisinin in traditional tea preparations of Artemisia annua?, Trans. Of the Royal Society of Tropical Medicine and Hygiene, Vol. 100. Issue 8, p 802.
15. Newton, Paul et. al., (2006), ?Manslaughter by Fake artesunate in Asia - Will Africa Be Next??, Plos Medicine, Vol.3, Issue 6, p e197 www.plosmedicine.org.
16. Duffy, Patrick E and Mutabingwa Theonest K, (2006), Artemisinin Combination Therapies, The Lancet, 367, pp 2037-2039.