Without any doubt, the isolation of artemisinin from the Chinese medicinal plant Artemisia annua (1972) and the use of semi-synthetic medicines from artemisia have widened the range of treatment for malaria. Numerous studies in tropical countries have already demonstrated the very great potential of artemisia based medicines.

In contrast, we know of no clinical studies of the effectiveness and safety of tea preparations from the dried leaves of artemisia. This is somewhat surprising, given the fact that there has been much written about the use of such tea in traditional Chinese herbal medicine for over a thousand years, and it is included in the current Pharmacognosy of the Peoples’ Republic of China.

Medicines from artemisinin derivatives are also available in the large towns of Africa. In towns such as Kampala, Uganda, and Nairobi, Kenya, the price is between $10 and $15. It is, therefore, on grounds of cost, inaccessible to the greatest part of the African population.

Hybrids of Artemisia annua are already cultivated for commercial export in countries such as Madagascar and Tanzania. Also, our own experiences show that one particular hybrid, which we have named “Artemisia annua anamed”, or “A3“, can be cultivated in Central Africa.

For these reasons, since 1997, ANAMED has investigated whether leaves from this hybrid, which are rich in the essential ingredient artemisinin, can be cultivated locally and used to treat of malaria. ANAMED centres which already use Artemisia annua are asked to keep a strict record of their clinical experience, and to share their results with other groups in the network. So far we have data from three centres, which are summarized in this paper.

Manner of use

One litre of boiling water is poured onto 5 g dried leaves of artemisia annua anamed. It is allowed to brew for 10 to 15 minutes, and then poured through a sieve. This tea is then drunk in four portions in the course of the day. The period of treatment is between 5 and 7 days.

Results

Three participating groups in the D.R Congo have sent detailed reports with information about the individual patients, any side-effects and their clinical progress, as well as the results of laboratory tests. These three studies were all made with the agreement of the local government doctors, and with the informed agreement of the patients concerned.

1. Nebobongo

We have already presented the results from Nebobongo (North-east D.R.Congo, near the town of Isiro). Of 48 patients who were admitted to hospital with the classical symptoms of malaria, and who were found to have malaria parasites (all P. falciparum) in their blood, after 5 days treatment 44 (92%) had blood free of parasites. 37 patients said they were totally without symptoms, while 11 patients complained of some discomfort, 3 of them had headache, 1 fever, 4 pains in the joints and 1 giddiness.

The patients showed no significant side-effects. 11 (25%) reported feelings of sickness, though no patient actually vomited. In this investigation, no measure of the density of parasites in the blood was made, though after treatment no patient had a relapse. Nebobongo is in an area where malaria is completely endemic, the patients were all over 18 years old and had only ever lived in areas where malaria is endemic. They were all patients of the leading doctor of Nebobongo Hospital, and the laboratory tests were undertaken by qualified laboratory assistants.

2. Lwiro, Bukavu

Lwiro is about 60 km north of Bukuvu, in the north-east of the D.R.Congo. Under the leadership of biologist Innocent Balagizi and the care of the nurse and a laboratory assistant in the regional health centre TALKIS in Lwiro, a total of 91 patients were treated with artemisia tea for five days between February 1998 and August 1999. Each patient had come to the health centre with symptoms typical of malaria, and all were shown to have plasmodium in the thick blood smears (59 patients; P. falciparum, 15; P. malariae, 15; both P. falciparum and P. malariae and 2; both P. falciparum and P. vivax). These patients had all almost exclusively lived in areas in which malaria is endemic, so they had a significant immunity to malaria. Five of the patients were under 18 years old (17 months, 19 months, and 10, 11, and 17 years).

Following treatment, no parasites were to be found in the blood of 86 of the 91 patients (95%). Whilst being treated, 21 patients complained of giddiness, 11 of feelings of sickness, 10 of noises in the ears, 8 of eye problems, 2 of itchiness and 2 of stomachache. 31 of the 92 patients said that they had no new complaints. The thick blood smears were negative following treatment for each of the five children.

For 24 patients, the parasite concentration in thick blood smears was determined before treatment and on every second day up to the eighth day following the first treatment. Before treatment between 4 and 175 parasites were counted in the field of view. The number decreased markedly in the first two days, and a zero count was found between the fourth and sixth days. On the fourth day, parasites were still to be found in the blood of 14 patients, on the sixth day of 4 and on the eighth day no patients had parasites in their blood (one patient showed no clinical improvement by the fifth day of treatment and was transferred to hospital).

The progress of 31 patients was regularly checked following treatment. When discharged, tests showed that none of them had any parasites in their blood. Within the first month, 4 patients (13%) were once again positive, in the second month 2 patients (6%), in the third month 6 patients (19%) and in the fourth month after treatment 7 patients (23%). In this area in which malaria is endemic, after 4 months 50% of the patients had a measurable parasitaemia.

3. Kinshasa

21 patients were treated with artemisia tea for seven days in the Red Cross Health Centre, 75 Av. Loya, Kinshasa 1, under the supervision of Ethnopharmacologist Konda Ku Mbuta. Two doctors, two nurses and a qualified laboratory assistant work in this hospital.

The patients arrived at the Out-patients Department with symptoms typical of malaria, and each produced a positive think blood smear. We have records of the parasite concentrations for 13 patients; for whom the number of trophozoites in the field of view was between 2 and 10. All the patients were over 18 years old. During treatment, two patients complained of stomachache, one of colic and one of giddiness. One patient had a fever until the third day of treatment, and another until the last day. One patient had already been treated intravenously with quinine, and one patient, who showed advanced symptoms of AIDS, died two days after treatment. With regard to the immunity of the patients, we can say that in the inner-city area of Kinshasa malaria does not appear to be endemic. It could be therefore that only some of the patients are semi-immune.

After 7 days treatment with artemisia tea, the blood smears of 19 (91%) of the 21 closely monitored patients were negative. The smears of two patients still contained a few trophozoites. According to the statement of the Health Centre, of the 21 patients, 20 showed a good clinical recovery.

Discussion

Observations are presented of the effectiveness of artemisia tea from three centres in the Democratic Republic of Congo. The three health centres operate completely independently from each other. ANAMED in Germany provides an exchange of information. According to the data presented here, a recovery rate of over 90% was observed, if one takes as the criterion the absence of asexual forms of plasmodium on the last day of treatment. Also the clinical side-effects appeared to be satisfactory as judged by the vast majority of the patients, even allowing for the difficulty of being totally objective on this score.

In areas where malaria is endemic, it is sometimes hard to tell whether or not malaria is actually the cause of the presented symptoms. Parasites are often present in the blood of semi-immune people who show no malaria symptoms. The actual causes, particularly with people with a low parasite count, can therefore be difficult to ascertain. The investigations presented here do not completely clarify this problem. We do emphasize, however, that the data presented here originates from patients who, in the clinical judgement of doctors and nurses, were ill with malaria and needed treatment with antimalarial drugs.

The positive results could, on the other hand, be achieved as a result of the (secret) additional use of chloroquine or quinine. In the Congo chloroquine can be bought without prescription, and in the region around Bukavu quinine can be extracted from the cinchona tree, from which a traditional preparation can be made and used. The results presented here should not be treated, therefore, as one would standardized data from clinical studies.

An exact record of the concentration of parasites in the blood of the patients who were treated is not available, only the average parasite count per visual field. If one accepts the simplification that 0.002 microlitre blood is shown in the visual field (11), then the average concentration of parasites was 4,800 per microlitre (using the records of 36 patients), that is a rather high concentration of parasites for semi-immune patients (12).

With all the semi-synthetic artemisinin derivatives (Artemether, Arteether and Artesunate), there is a recrudescence rate of up to 50% (3).That means that there is a minute count of plasmodium, that cannot be detected with the microscope, that survive the treatment, and multiply themselves again until they are in sufficient number to cause a reinfection. Because of the short half-life of artemisinin, a recrudescence within the first four weeks after treatment can be expected (13). Results from Bukavu show new evidence of 13% of treated patients having malaria parasites in the blood within the first month. Although in an area in which malaria is highly endemic one can scarcely differentiate between a recrudescence and a new infection, one must take the problem of recrudescence with artemisia tea treatment into account. To make an accurate assessment of the recrudescence rate in any given locality one must make an examination of the plasmodium using DNA tests.

Altogether, the results from each of the three centres demonstrate a very pronounced effectiveness of artemisia tea. In areas in which there is absolutely no possibility of obtaining plentiful supplies of antimalarial drugs, this treatment would have great potential if artemisia could be cultivated locally. It is important to note that artemisia tea is not a new development, it has been used extensively to treat malaria in traditional Chinese medicine (6). With a traditional medicine whose use has been proved over several hundred years (5), the danger of serious side-effects is much less than with a newly developed drug. In view of the fact that Artemisia annua is completely new in African traditional medicine, one must attach the greatest importance to the earlier recognition of problematical side-effects. The undesirable effects of seeing and hearing difficulties were reported only from Bukavu, not from the other centres. In the Bukavu region there are extensive plantations of cinchona trees, and, since these particular side-effects are well recognized as resulting from treatment with quinine, it remains questionable as to whether these really are genuine side-effects of artemisia tea.

The reports of previous investigations underline the necessity of confirming the observed results by means of a clinical study. In my opinion an open, random and carefully controlled study would be most appropriate. The practicality of conducting such a project in field conditions was recently discussed (14). There should be a control group of patients, who are treated with chloroquine or with another standard treatment of the particular region. It would be important to supervise the daily consumption of the tea, and to exclude any possibility of the additional use of another antimalarial drug during the study, for example through the qualitative proof of chloroquine metabolism in the urine before and after treatment (15). Further, important epidemiological data about the region must be known, e.g. is malaria endemic, is transmission stable or unstable (i.e. whether the incidence of malaria is constant throughout the year, or whether it varies because of other factors, e.g. the weather or humidity), the morbidity and mortality of the population regarding malaria, the situation with regard to resistance. Also important are not only the standardized documentation of the clinical symptoms and the laboratory results (with measurements of the parasite concentration standardized on a count of 200 Leukozytes) during therapy, but also observations of the patients and results of laboratory tests for four weeks after the end of the treatment.

Countrywide Use? Pros and cons

Disadvantages: Very effective healing plants can, in general, also cause strong side-effects. Given the correct dosages, the isolated ingredient artemisinin seems to produce virtually no side-effects. Tea made from the leaves, which extracts many components, has been used for thousands of years in Chinese traditional medicine, though no clinical studies have been conducted. Careless usage could lead to the development of resistances. For this reason, some scientists, e.g. at the University of Tübingen, warn against its widespread use at the present time.

Advantages: The problem is very urgent. Every 12 seconds, somewhere in the world, somebody dies from malaria. The not altogether easy cultivation of Artemisia annua, and the bitter taste of the tea, will ensure that this plant will not be used to excess. In 161 recorded cases, over 90% of people were healed using artemisia tea. These were native people, and therefore semi-immune, in three clinics in the Dem. Rep. Congo (see above).

In this situation, one can understand if particular ANAMED groups (such as ANAMED Tanzania, or ANAMED South-Uganda) recommend country-wide cultivation, or, like anamed Congo South Kivu, already cultivate artemisia at several clinics around the town of Bukavu. One cannot expect any one country to undertake a clinical study of the efficacy and side-effects of artemisia tea. Much less can one expect this to be undertaken by a pharmaceutical company, the meagre profits from the sales of tea would never cover the costs of the research. Further, people would be encouraged to produce their own teas, and so the profit from established drugs (Lariam, Doxycyclin, Fansidar…) would be endangered. Empirical observation must therefore suffice, until such time as a humanitarian organization is willing to finance clinical studies.

The extent to which the use of artemisia tea is recommended must be left to the scientists in the current national ANAMED groups. National research institutes (in Uganda, Makerere University, in Congo, Centre de Recherche en Sciences Naturelles, Bukavu and Centre de Recherche en Sciences de la Santé, Kinshasa….) are involved in these decision-making processes, and are in a position to advise national health officials.

The ANAMED coordination in Germany has committed itself to:

– making hybrid seeds available
– providing information about cultivation in the tropics
– recording the effectiveness and side-effects, and publishing the results in the national
– languages of southern countries, as an aid to decision-making.

The decision as to how widespread the cultivation of Artemisia annua should be in a particular country must remain with the national authorities. Their analysis of the balance between its usefulness on the one hand and the risks on the other is a step towards achieving some independence from multinational pharmaceutical firms, to having a legitimate voice on health issues and to more democracy in the field of health.

Dr Hans-Martin Hirt, ANAMED Coordination, Winnenden, Germany

References

WHO. Assessment of therapeutic efficacy of antimalarial drugs. WHO/MAL/96.1077. Geneva. WHO 1996.
Guo-Qiao Li, Xing-Bo G, Lin-Chun Fu, Hua-Xiang Jian and Xin-Hua Wang. Clinical trials of artemisinin and its derivatives in the treatment of malaria in China. Trans. Royal Soc. Trop. Med. Hyg. (1994), 88, Suppl. 1, 5-6.
Tran Tinh Hien. An overview of the clinical use of artemisinin and its derivatives in the treatment of falciparum malaria in Vietnam. Trans. Royal Soc. Trop. Med. Hyg. (1994), 88, Suppl. 1, 5-6.
Nosten F. Artemisinin: large community studies Trans. Royal Soc. Trop. Med. Hyg. 88, Suppl. 1, 45-46.
Woerdenbag H J, Pras N. Artemisia annua L. Der einjährige Beifuss. (1991) Z Phytotherapie 12:133-139.
The Peoples Republic of China. Pharmacopoeia. Vol 1. Beijing: The People’s Health Publisher, 1985.
Delabays N. Biologie de la Reproduction chez l’Artemisia annua L. et Génétique de la Production en Artemisinine. (1997) Thèse de doctorat. Faculté des Sciences de l’Université de Lausanne.
In the Moshi region, Tanzania, Personal observations.
Mueller MS; Karhagomba IB; Hirt HM; Wemakor E. The potential of Artemisia annua L. as a locally produced remedy for malaria in the tropics: agricultural, chemical and clinical aspects. ( Non published data ).
Action for Natural Medicine (ANAMED), c/o Dr. Hans Martin Hirt, Schafweide 77, D-71364 Winnenden, Germany.
Petersen E, Marbiah NT, New L, Gottschau A. Comparison of two methods for enumerating malaria parasites in thick blood films. Am J Trop Med Hyg 1996; 55: 485-9.
Shute GT. (1988) The microscopic diagnosis of malaria. In: Wernsdorfer WH, McGregor I (eds). Malaria. p.805, Churchill Livingstone, Edinburgh.
Seidlein L, Bojang K, et al. A randomized controlled trial of Artemeter/Benflumetol, a new antimalarial and pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria in African children. Am. J. Trop. Med. Hyg. 58(5), 1998, pp 638-644.
Willcox M L. A clinical trial of ”AM”, a Ugandan herbal remedy for malaria. J Pub Health Med (1999)21(3), 318-324.
Betschart B, Sublet A, Steiger S. (1991) Determination of antimalarial drugs under field conditions using thin layer chromatography: Journal of Planar Chromatographie. Vol. 4, p 111 -114.

Addresses of the participating groups

ANAMED Germany, c/o Dr. Hans Martin Hirt, Schafweide 77, 71364 Winnenden, Germany. Email: anamedhmh(at)yahoo.de

Innocent Balagizi, Centre de Recherche en Sciences Naturelles, Lwiro, D.R. Congo. Email: Infobukavu(at)bushnet.net

Konda Ku Mbuta, Centre de Santé de Croix Rouge, B.P.11.165, Kinshasa 1, D.R.Congo. Fax : via 001 212 656 1937. Email: anamed_kin(at)yahoo.fr

Dr. Markus Müller, Vogelsangstr. 7, 72144 Dusslingen, Germany. Email: MarkMueller(at)t-online.de