A comparative study of the traditional remedy ''Suma-kala'' and chloroquine as treatment for malaria in the rural areas

NOUHOUM KOITA

The Clinical Section
Traditional Medicine Division
P.O.Box 1746, Bamako, Mali.

Introduction

Traditional medicine has been utilised by the majority of the World population for thousands of years. Until the beginning of the 19th century, all medicine was traditional (Jellife, 1977). Yet in many developing countries it is true that for the majority of the rural population traditional medicine is the only primary or any other kind of health care available (Heggenhougen et al., 1988). For more than 70% of the population in Africa, traditional medicine is the first, if not the only health care system available in the poor rural and urban areas. In recognition of this fact, the World Health Organization underlined the potential role that traditional medicine may play in reinforcing the health care system through the primary health care approach in developing countries (W.H.O., 1978). The value of traditional medicine may be relative to both its pharmacological and/or biomedical value, as well as its psychological and social values (Heggenhougen et al., 1988).

Medicinal plants and their products have been used in the treatment of malaria throughout the tropics and subtropics. Such experience is not to be ignored. Instead, it should be actively investigated so that basic information can be made available for the preparation of standardized, effective and non-toxic remedies. Quinine, from the bark of Cinchona, whose legend dates from the 17th century (Bruce-Chawatt, 1985; Phillipson, et al., 1986) is an outstanding example of a plant product which has been used for centuries in the treatment of malaria. The Chinese antimalarial, quinghaosu, is another example of this kind. The Ministry of Health in Mali has been trying to study the resources of Malian traditional medicine, with emphasis on the evaluation of the effectiveness of its medicinal plants.

The main purpose of this paper is to analyse and discuss the results of a clinical trial which compares a Malian traditional remedy called "Suma-Kala", with chloroquine, as a treatment for malaria in the rural areas of Mali.

Materials and Methods

A randomized controlled trial of "Suma-Kala" in the treatment of malaria was carried out at the Selingue Health Center, from July to September, 1987.

Preceding the main study, a two weeks training and pilot study took place in the Selingue Health Centre, attended by all personnel involved in the study. The aims of these were to review and standardize the clinical and laboratory techniques and also to test and correct the material and methodology. The ethical problems of the study were discussed. Any complicated case was to be admitted immediately to the health centre for proper management.

Preparatory visits were paid to the local authorities by the doctor of Selingue Health Centre and his team, to explain the objectives of the study, and to ask for their approval and cooperation.

Objectives of the study

The objectives of the study were:

(a) to confirm the antimalarial property of the "Suma- Kala";
(b) to assess the acceptability and tolerance of the "Suma- Kala"; and
(c) to compare its activity with that of a well established standard antimalarial, which, in our case, was chloroquine.

Study area

The study was conducted in four villages in the Selingue area during the rainy season, from July to September in 1987 (Figure 1). Selingue is the National Institute of Public Health Research's rural health centre, in a dam area which deals with water-related diseases. Selingue is 135 km from Bamako. The background information about Selingue area is adapted from Traore (1986).

Human population and randomization

The method used consisted of a randomized control, and partially blind clinical trial. The four villages closest (from 3 to 10 km) to the health centre were chosen for a good follow up and case management in the event of complications. The chief and the health committee of each village chose the place (rooms) where the examination of the patients took place. All patients who thought had "sumaya" (malaria fever) were invited to attend the clinical examination.

All the patients were randomized on their arrival on day 0 and treated. The patients were randomly allocated to the "treatment" group ("Suma-Kala") or the "control" group (chloroquine) alternatively in a group of 10 on arrival. The method of "tossing a coin" was used to decide the order of allocation For the purpose of this study, the patients were told that they were receiving traditional remedies made by the Traditional Medicine Division of their own country by their own countrymen. The treatment was administered on an outpatient, basis. Neither the patient nor the medical team was blind to the treatment since the chloroquine was administered in capsules while the "Suma-Kala" was given as a decoction.

The patients were also questioned on the first day (day 0) about the recent prophylaxis and treatment and their urine was tested for presence of detectable concentration of chloroquine, amodiaquine, quinine, quinidine or mefloquine using the Dill-Glasko test.

A positive result of the Dill-Glasko test excluded the patient from the study. Any patient younger than 5 years and any pregnant woman was excluded.

The following conditions also excluded patients from the study:

(a) parasitaemia less than 5000 malaria parasites per cubic mm of finger blood smears;

(b) serious illness conditions such as, liver and kidney failures, acute or chronic pneumonia, hepatitis, and allergy;

(c) presence of serious digestive troubles such as, diarrhoea, intensive vomiting; and

(d) signs of dehydration.

Fig. 1: Map of Mali

Two teams were responsible for the study: one team in the field was in charge of the clinical examination and the blood film preparation without knowing the parasitaemia progress; and the second examined parasitaemia in the laboratory in Selingue Health Centre, without knowing which drug the patient had received. Only the result of the first blood smear (day 0) was communicated the following day (on day 1) to the clinical examination team for exclusion from the study of any patient with a parasitaemia less than 5000 of parasites per cubic mm on the first day (day 0). The other results of parasite count (days 1,3,5,7,14 and 21) were kept secret by the head of the laboratory team until the end of the study. On the other hand, the laboratory team members could not distinguish whether a slide they were examining belonged to a patient under the new drug or not.

Preparation of the drug

Both treatments were administered orally and were continued for seven consecutive days. The chloroquine diphosphate was made by our partners in France for the purpose of the study and presented in 100 milligramme and 300 milligramme capsules. Empty placebo capsules similar to those of chloroquine were made in France and sent to us by "CREDES, Terre des Hommes".

"Suma-Kala" was analysed botanically, chemically and pharmacologically. The detail on its botanical, chemical and pharmacological preliminary studies are available elsewhere in the Traditional Medicine Division in Bamako, Mali (Study of "Suma-Kala" presented to the 1988 meeting of the Scientific Committee of the National Institute of Public Health Research in Bamako).

The "Suma-Kala" is composed of three medicinal plants including Cassia occidentalis L. (locally known as: Mbala mbala), Lippia chevalieri Moldenke (locally known as: Kaniba djan); and Silanthus oleraceae Jacq. (locally known as : Mame - Farimani) (Figures 2, 3 and 4).

"Suma-Kala" was prepared by the galenic section of the Traditional Medicine Division in its laboratory in Bamako, Mali. It was a mixed powder of the leaves of Cassia occidentalis L. and Lippia chevalieri M. and of the flowers of Spilanthus oleracea J. It was presented in a small plastic bag each containing 10 grams of this mixture of powder with the following proportions:

Cassia occidentalis L. 64%
Lippia chevalieri M. 32%
Spilanthus oleraceae J. 4%

Although the population in rural areas in Mali are used to decoction preparation, the patients randomised to "Suma- Kala" were shown on the first day (day 0) how to prepare the decoction. Subsequently they were required to prepare the decoction for themselves daily at home. The decoction was prepared by boiling a bag of 10 grams of "Suma-Kala" in a half litre (500 ml) of water for about 15 minutes. Sugar can be added to sweeten its taste.

Dosage

The treatment was administered to the patients at home (outpatient). The chloroquine treatment was standardized and consisted of swallowing 10 milligrammes per kilogramme body weight during three consecutive days. For the remaining four days of the week, the empty placebo capsules were given so that the duration of the treatment for both drugs lasted for seven consecutive days.

The treatment with "Suma-Kala" consisted of drinking the decoction made from "Suma-Kala", twice a day, for four days, and then once a day for three days. The quantity of "Suma kala" bags and chloroquine capsules for the daily treatment were given to the patients each day after the clinical examination and the making of the blood film for parasitaemia count.

Clinical parameters

A form was used to record each patient's identity and the clinical parameters each day of examination. The biological parameter (parasitaemia) was recorded separately in the laboratory record. In addition to the identity (name, sex, age, village, date of examination, and the observer's name), the clinical record included the follow up of auxiliary temperature, headache, vomiting, shivering, nausea, and the side effects such as allergy and digestive troubles (see copy of the form in annex). These clinical parameters were recorded every day from day 0 (first day of examination) to day 7 (eighth day of examination) for assessing the curative effect of the drugs; and also on days 14 and 21 for assessing the eventual residual protective effect of the drugs.

Figure 2: Habit drawing of Cassia occidentalis

Figure 3 : Habit drawing of Spilanthus oleracea

Flgure 4: Habit drawing of lippia chevalieri

Laboratory methods

The laboratory method used was the malarial parasite count from finger thick and thin blood smears, using the W.H.O. standard techniques (W.H.O., 1984).

The labelling of the slides was carried out with a diamond pencil. The finger of the patient was cleaned with 70% ethanol. Staining of blood was done using Giemsa stain. The films for malaria parasites were collected in the field during the clinical examination on days 0, 1, 3, 5, 7, 14 and 21. All blood films collected were read in the first instance in the laboratory of Selingue Health Centre and cross checked after one month in the parasitology Department of the Medical School in Bamako. The laboratory observer teams were composed in Selingue by the two laboratory technicians under the supervision of the parasitologist head of the laboratory, and in Bamako by one laboratory technician and the physician parasitologist, head of the Parasitology Department of the Medical School.

The thick films were examined using the "farmer ploughing his field" technique: across the film to the opposite edge, and a slight lateral move, then back across the film, a slight lateral move. The process was repeated. For the thin films a "battlement" technique was used traversing the edge of the tail in short vertical and horizontal tracks. The number of parasites per 200 White Blood Cells were counted and parasite density was calculated taking 8,000 WBC per cubic mm as an average WBC count. A simple mathematical formula was used to convert the counts into the number of parasites per cubic mm of blood. For the minimum threshold, W.H.O. suggests 1000 parasites per cubic mm (W.H.O., 1984), but we decided to use 5000 parasites which is according to findings in Africa (Trape, 1985), a useful discriminant for separating children in whom malaria was thought to be the cause of their illness, from those in whom it probably was not. This was because of the fact that most patients in endemic areas of malaria like Selingue, could have a parasitaemia up to 1000 per cubic mm without showing the clinical signs of malaria. Therefore, any patient with a parasite density less than 5000 per cubic mm was excluded from the study.

Data analysis and reports

It was planned to carry out a computer analysis of the data and also at the Statistics Unit, the National Institute of Public Health Research in Bamako, using appropriate statistical tests (Z-test or t-test or Mantel-Haenszel test) to compare the effects of the two drugs. The results were supposed to be diffused at the different levels of utilisation.

Results of the clinical trial

About 3000 people presented with "sumaya" were included in the study. All were randomised on their arrival, then examined and their complaints were examined and treated if necessary. However, according to the criteria for inclusion in the study, only 53 of these patients were eligible for comparing "Suma-Kala" and chloroquine from July to September 1987 in Selingue. Thirty-six of the patients belonged to the "Suma-Kala" treated group and 17 belonged to the chloroquine treated group.

Age and sex distribution

The age and sex distribution is shown in Table 1. The study population was very young: 70% of the 53 patients were under 10 years. Only one patient was older than 25 years (she was 45 years old). Fourty-five percent of the patients were males and 55% were females. The results of the Mantel-Haenszel test have shown that the sex difference between the two groups after allowing for age group was not statistically significant (c² = 0.030, with a degree of freedom = 1 and p > 0.05). On the other hand, the age group difference between the "Suma-Kala" treated group and the chloroquine treated group controlling for the sex was not significant (Mantel Haenszel c² = 0.030 with df = 1 and p > 0.05).

Table 1: Age and sex distribution of the study population per treatment

Age group	Suma-Kala			Chloroquine
(years)	Males	Females	Total	Males	Females	Total
5-9	13	11	24	5	8	13
10-14	2	4	6	1	2	3
15-49	2	4	6	1	0	1
TOTAL	17	19	36	7	10	17

Follow-up of the study population

Table 2 shows the follow up of the study population per day and age group. The overall proportions of drop-out before the end of the study were similar among the two groups and concerned mainly the first age group (5-9 years). Eighty-six percent of the patients in the "Suma-Kala" group completed the treatment, while 71% in the chloroquine group completed the treatment. Therefore, the follow up was 15% better in the "Summa-Kala" group on day 7. However, this difference between the proportion of patients who completed both treatments was not statistically significant (Z = 0.064, p = 0.95).

Table 2: Follow up of the treatment by the patients per day and per age group

"Suma-Kala" treated group							Chloroquine group
Days	5-9	10-14	15-19	24-25	45-49	Total	5-9	10-14	15-19	Total
0	24	6	3	2	1	36	13	3	1	17
1	24	6	3	2	1	36	13	3	1	17
3	23	6	3	2	1	35	10	3	1	14
5	20	6	3	2	1	32	8	3	1	12
7	19	6	3	2	1	31*	8	3	1	12*
14	18	5	3	2	1	29	8	3	1	12
21	17	4	3	2	1	27	6	3	1	10

Clinical parameters

Figures 5 and 6 show the proportions of patients who became free of the clinical parameters per treatment and per day of treatment. The comparison of the effects of the two drugs on the clinical parameters show that "Suma-Kala" was as effective as chloroquine, if not better.

We considered an auxiliary temperature of 37.5°C or higher as fever according to findings in Africa (Greenwood et al, 1987; Delfini, 1968; Cobban, 1960). The proportions of patients who had fever, headache, shivering, nausea and vomiting at the start (on day 0) and became free of these clinical parameters after 7 days of "Suma-Kala'' treatment were respectively 59.3 %, 76%, 62.5 %, 93.3%, and 79%, while the proportions of patients free of clinical parameters under chloroquine treatment were respectively 50%, 47%, 80%, 75%% and 68%. The general trend was suggesting a better improvement under "Suma-Kala". However, the difference of the effects of the two drugs against fever, headache, shivering, nausea and vomiting was not statistically significant (all p > 0.05). The same trend of better improvement of the clinical parameters on days 14 and 21 was noticed, but the difference was not statistically significant (p > 0.05).

Side effects

No clinical complication was noticed during the follow up of the patients in spite of the high parasitaemia at the start of the treatment. Few side effects were noticed. Three cases of allergy to chloroquine causing the treatment to be abandoned on day 3 were noticed among the chloroquine group, while none was reported among the "Suma-Kala" group. One case of constipation was declared among the "Suma-Kala" group, and none among the chloroquine group.

The "Suma-Kala" was very well tolerated by the patients. Table 3 shows the proportion of patients developing clinical parameters later, on days 3, 5 or 7, without having them at start. The differences between these proportions using Fisher's exact test were not statistically significant for all (p > 0.05), except for the allergy in which case "Suma-Kala" was better than chloroquine (p < 0.05).

Table 3: Proportion of patients developing clinical parameters later on days 3, 5 or 7 without having them at start

Parameters	"Suma-Kala" group	Chloroquine group
Fever	2/9 (22.2%)	1/7 (14.3%)
Headache	1/3 (33.3%)	1/2 (50%)
Shivering	1/4 (25%)	2/5 (40%)
Nausea	0/5 (0%)	0/13 (0%)
Vomiting	0/22 (0%)	0/14 (0%)
Allergy	0/36 (0%)*	3/17 (18%)*
Indigestion	1/36 (3%)	0/17 (0%)

* p < 0.05 using Fisher's exact test.

Biological parameters

Plasmodium falciparum was the only type responsible for the malaria infection in our study. The results of the biological parameters are shown in Tables 4 and 5 and in figure 7. These results suggested that chloroquine was more effective than "Suma-Kala" in cleaning the parasites of malaria from the finger blood smears.

Figure 5: Proportion of patients who had fever on day 0 and became free from it later per day and treatment

Figure 6: Proportion of patients with headache on day 0 but none later on per day and per treatment

Figure 7: MEAN LOG (PARASITAEMIA .1) PER DAY AND PER TREATMENT

Before the treatment started (on day 0), the overall geometric mean of parasite count was 17975.3 among the "Suma-Kala" group for a population of 36 patients, while among the chloroquine group it was 13414.3 for a population of 17 patients. The difference between the parasitaemia of the two groups using mean log (parasitaemia count + 1) was not statistically significant (t-test = 1.37, df = 51, and p > 0.05).

At the end of the 7 days treatment, the geometric mean of parasitaemia count became 153.8 among the "Suma-Kala" group for 31 patients, while in the chloroquine group it became 3.4 for 12 patients. The difference between the means of parasitaemia using the mean log (parasitaemia count +1) became statistically significant (t = 2.98, df = 41 and p < 0.05) (Table 4). These figures in Table 4 were suggesting that chloroquine was better than "Suma-Kala" in cleaning the malaria parasitaemia at the end of both treatments.

Table 4: Mean log (parasitaemia count + 1) and geometric means per day and per treatment

	"Suma-Kala" group			Chloroquine group
Days	log(cnt+1)N	SD	Geom. mean	log(cnt+1) N	SD	Geom. mean
0	4.2547 36	.3079	1795.3	4.1276 17	.3274	13414.3
1	3.8774 36	.6282	7539.5	3.0301 17	.9380	1046.4
3	2.9449 36	1.4131	880.0	1.3995 13	.9204	24.1
5	2.4817 32	1.4201	302.2	.7175 12	.8457	4.2
7	2.1898* 31	1.6239	153.8	.6417* 12	1.2096	3.4
14	2.3245 28	1.6530	219.1	.1165 12	.4036	3.0
21	1.8449 26	1.6094	69.0	.5454 10	.8921	2.5

* p > 0.05

Residual effect of the drugs

We expected the protective ("prophylactic" or residual) effect of "Suma-Kala" to be continued one or two weeks after the treatment like the way it usually happens with chloroquine. The data on days 14 and 21 (Tables 4 and 5) were for the study of these eventual residual effects.

The residual effects of "Suma-Kala" against the clinical symptoms of malaria were similar with those of chloroquine. However, the parasitaemia of 5 among the 18 patients of the "Suma-Kala" group with low parasitaemia (less than 1000 parasites per cubic mm) on day 7 (end of both treatments), became high (greater than 1000 parasites per cubic mm) on days 14 and 21, while the patients of the chloroquine group with low parasitaemia on day 7 remained with a low parasitaemia. The difference between these proportions (13/18 and 12/12 or 10/10) was statistically significant (using Fisher's exact test p < 0.05). Although the sample size was small, this result was suggesting that the residual protective effect of "Suma-Kala" was less than that of chloroquine on days 14 and 21.

Table 5 shows the proportions of patients with parasitaemia less than 100 per cubic mm per day and per treatment. At the end of the treatment (day 7), the difference between these proportions (58.1 % versus 92%) was not statistically significant (Z = 1.72 and p = 0.085 > 0.05).

On day 21 also, the proportions of patients with a parasitaemia less than 100 per cubic mm (63 % versus 100%) were not statistically significant (Z = 1.81, p = 0.07 > 0.05).

Table 5: Proportions of patients with parasitaemia less than 1000 per cubic mm per day and per treatment

Days	"Suma-Kala" group	Chloroquine group
0	0/36 (0%)	0/17 (0%)
1	3/36 (8.3%	10/17 (59%)
3	15/35 (43 %	13/13 (100 %)
5	17/32 (53.1 %	12/12 (100 %)
7	18/31 (58.1 %)	11/12 (92%)*
14	16/29 (55.2 %)	12/12 (100 %)
21	17/27 (63 %)*	10/10 (100 %)*

* p > 0.05

Discussion of study design and results

A good study design should be made in such a way that any observed difference between the treatment and the control group can be attributed to the real effect of the treatment.

We thought of using the randomized double blind placebo control trial but unfortunately, the drug section could not make placebo for the "Suma-Kala", and it was impossible to make the leaves composing "Suma-Kala" unrecognizable. On the other hand, because of ethical consideration, a control group receiving no treatment or placebo was not thinkable. We finally ended up with a randomized control blind method.

Whenever possible, it is preferable that neither the participant nor the investigator knows which treatment has been received until after the end of the trial.

For future trial if the drug section is able to make a placebo preparation indistinguishable to "Suma-Kala", then we can achieve a double blind method by giving to the control group chloroquine capsules plus a placebo decoction and to the treatment group "Suma-Kala" decoction plus placebo capsules. We randomized alternatively by group of 10, the patients declaring having "Suma-Kala" (malaria) on their arrival to the control and the treatment group. The method of "tossing a coin" was used to decide the order of allocation. The patients were unknown by the examiners and therefore this limited the selection bias. However, the randomization method we used could be improved for instance by randomizing only the eligible patients and by using random number tables with odd numbers (1,3,5,7,9, etc.) corresponding to the chloroquine treated group and even numbers (0,2,4,6,8, etc.) to the "Suma-Kala" treated group (or vice versa).

Instead of numbers, different combinations of letters could also be used to randomize the patients (i.e., AABB, ABBA, ABAB, BBAA, etc., where A is for the control group and B for the treatment group, or vice versa). The order of allocation should be preferably decided before the start of the trial. It is sometimes also desirable to arrange the allocation so that equal numbers of participants will be entered into each group. That is what (Kirkwood (1988) called "restricted randomization" or "randomization with balance."

We had a lot of trust on the patients for following correctly the instruction for the preparation of "Suma-Kala."

The urine of the patient became positive to the Dill- Glasko test, like it happened with chloroquine. Therefore Dill-Glasko test was not performed after day 0 to check whether patients on "Suma-Kala" also gave themselves chloroquine. This could perhaps be avoided by doing the study on patients basis in which case one would have to think about selection biases. For future trials we should find a way to perform spot check.

There is no perfect approach and the field conditions are such that compromise between theory and reality is obligatory. What is essential is to be as close as possible to the ideal as the conditions permit it. The fact that our population was very young, may be due to the high level of our threshold of 5000 parasites per cubic mm, which is easier to get among the young people because the older people in a high endemic area may have already developed their semi-immunity to malarial infection (Bruce-chawatt, 1985; Trape, 1985).

Because of the conditions required for the inclusion in the study, our sample collected during three months seems small. Most of the people of Selingue very often take chloroquine in all cases of fever or for prophylactic purpose. Therefore, the urine in most of the people was positive for the Dill-Glasko test. In these conditions, a reasonable sample size was difficult to obtain in three months and the resources available could not permit a longer stay.

The results so far of the study are interesting for several reasons. To our knowledge this study is perhaps one of the first (if not the first) clinical trials comparing African traditional antimalarial medicinal plants and allopathic antimalarial drugs.

Some preliminary work has been done in some countries but not published (Bray, personal communication). Most of the studies published referred to in vivo experiments on mice infected berghei (Makinde and Obih, 1984; Peter, 1970) or in vitro (Phillipson et al., 1986).

The plants which composed "Suma-Kala" were known in West Africa and used in traditional medicine against several diseases.

Cassia occidentalis L. was the most popular, and the most used by the traditional practitioners mainly against malaria fevers, headache and skin diseases (Kheraro, 1974; Ayensu, 1978; Rozat, 1979; Oliver, 1986, Sofowara, 1982).

The findings have shown that C. occidentalis has antiparasitic and antibacterial activities (Oliver, 1986). Spilanthus oleraceae J. was known too, and used as a medicinal plant in West Africa (Kheraro, 1974; Rozat, 1979). The extracts of its flower-heads killed Anopheles larvae and the whole plant has shown insecticidal properties (Oliver, 1986).

Lippia chevalieri M. was the least popular among the plants which composed "Suma-Kala." However, it was also used as a medicinal plant in West Africa (Kheraro, 1974; Rozat, 1979).

The results of the study have shown that "Suma-Kala" is as effective as chloroquine against the symptomatic signs of malaria. Therefore, the traditional practitioners are quite right in using these medicinal plants against malaria because their diagnosis and prognosis of the disease are mainly based on clinical symptoms.

The current dosage of "Suma-Kala" was less fast than that of chloroquine in suppressing the malaria parasitaemia. The difference between the proportion of patients with parastitaemia less than 1000 parasites per cubic mm, was not statistically significant at the end of the treatment (day 7). However, the difference between the mean log (parasitaemia count + 1) of the two groups was statistically significant. Therefore, chloroquine was more effective than "Suma-Kala" in clearing the parasitaemia.

A parasitaemia of 1000 per cubic mm of finger blood smears is common among the people living in endemic areas like Selingue, and is well tolerated. That is why WHO suggested it as a cut off point (WHO, 1984) and (Trape 1985) suggested a higher level of minimum threshold of 5000. If we consider a parasitaemia of 1000 per cubic mm as "normal" in endemic areas during a period of high infection (raining season) as suggested by many authors (W.H.O., 1984; Trape, 1985; Greenwood et al., 1987), "Suma-Kala" and chloroquine could be considered as having similar effects against malaria, because the difference between the proportion of patients among the two groups having a parasitaemia less than 1000 parasites per cubic mm was not significant at the end of treatment.

It could be interesting to compare the effect of "Suma- Kala" to that of a placebo. But for ethical reasons, a placebo group was not used in our study, and in the literature we did not see any publication referring to placebo effect on malaria. Nevertheless, no case of complication was noticed among our patients in spite of very high parasitaemia cases (some were as high as 80,000 parasites per cubic mm). Furthermore, the difference between the biological parameters (proportion of patients with a parasitaemia less than 1000) on one hand, and between the clinical parameters (proportion of patients with fever, headache, vomiting, nausea, shivering) on the other hand, were not statistically significant. And also, the likely pattern of high parasitaemia in untreated malaria would be the occurrence of clinical malaria with a certain number of complications (for instance convulsions in children) and probably some cases of deafness. Therefore, we were convinced that the effect of "Suma-Kala" was far more than that of a placebo.

The two drugs were well tolerated, but "Suma-Kala" was better tolerated than chloroquine. This was illustrated by three facts. Firstly, the study did not show any side effect from "Suma-Kala", while 3 patients among the chloroquine treated group abandoned the treatment on the third day because of the allergy to chloroquine that they developed. Secondly, the difference between the proportions of patients who have developed later on clinical parameters without having them at start was not statistically significant, except for the allergy to chloroquine noticed among the chloroquine group. Thirdly, the follow-up of the treatment by the patients was 15 % higher among the "Suma-Kala" group.

An attempt was made to measure the protective (residual or "prophylactic") effect of the drug by looking at the clinical and biological (parasitaemia) parameters on days 14 and 21. The interpretation of the data on days 14 and 21 was difficult, because of the size of the sample becoming smaller on one hand, and on the other hand, these data are rather related to the eventual residual protective effect than to the prophylactic effect. Nevertheless, the two drugs seemed to have the same residual protective effect against the clinical parameters, but concerning the biological parameter, "Suma-Kala" seemed to have a less protective effect against malaria reinfection than chloroquine.

Conclusion

Research into medicinal plants should not stop because the herbal medicine still has an immense potentiality to enrich the universal pharmacopoeia.

Although the cooperation between allopathic and traditional medicine is not easy to build, it is necessary because it represents a valuable national resource for many developing countries. Therefore, it should be taken into account for the achievement of the World Health Organization goal of an ideal health for all. In Mali, as elsewhere, the research into traditional medicine should be extended beyond the focus on phytotherapy, and efforts should be made to do more research in the other aspects of traditional medicine because they heal people, even though they may not cure disease. The Malian traditional antimalarial remedy, "Suma-Kala", is working. The study showed that it is as efficient as chloroquine against the clinical symptoms such as fever, headache shivering, vomiting, and nausea, and also that it was better tolerated. However, "Suma-Kala" was not as fast as chloroquine in clearing malaria parasitaemia.

More research should be done in order to improve the mode of administration of "Suma-Kala", and to increase its speed of clearance of malaria parasitaemia. For instance, more research on its dosage and galenic presentation could improve its effects. Although the study has shown interesting results, its design, particularly the sampling method and the 'blindness', could be improved for future clinical trials. A randomised blind control trial could be applied, provided that a placebo for the "Suma-Kala" is available, so that the "control group" will receive chloroquine capsules (or the standard treatment) plus placebo (decoction), and the "treatment group" will receive "Suma-Kala" (or the new drug), plus placebo (capsules).

Meanwhile, the production and commercial exploitation of "Suma-Kala" in Mali should not be delayed. The plants which compose "Suma-Kala" are locally available and could also be locally cultivated. Therefore, the production of "Suma-Kala" should be regarded in the perspective of reducing the burden of drug importation, and also as a potential alternative source of income for the peasants.

Acknowledgements

I am grateful to Prof. Mamadou Koumare for the initiation of contemporary research into traditional medicine in Mali; Ms Gillian Maude for providing invaluable assistance and encouragement in preparing this paper; Drs. Kris Heggenhougen, Thierry Mertens and Dorothy Bray for reading early drafts and giving useful feedback; Drs. Drissa Diallo, Ogobara Doumbo, Moctar Guindo, the people and the personnel of the Selingue Health Centre, and the personnel of the Traditional Medicine Division for actively taking part in designing and implementing the study; Dr. Martin Vitte and her colleagues from "CREDES, Terre des Hommes, France" for funding of the study and the British Council for sponsoring my MSc. course in England.

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