Background: Adansonia digitata L. (Malvaceae), also known as baobab, is a tree attracting recent interest especially due to the high nutritional value of the fruit pulp. However, few studies are reported on the secondary metabolite content, showing high variability depending on the geographic region. Methods: In this study, the chemical profiles of Malian commercial baobab fruits and leaves, focused on phenolic content, were investigated by HPLC coupled with a photodiode array (PDA)/UV and an electrospray ionization (ESI) mass spectrometer (MS) and gas chromatography (GC)/MS. In addition, the extracts of fruit pulps obtained from three different markets (Fruits 1, 2, and 3) were evaluated for their total phenolic content (TPC), antioxidant activity and α-glucosidase inhibition. Results: Baobab fruit pulps were found to be rich in procyanidins and flavonol glycosides, with tiliroside as the major constituent. The baobab leaves showed a similar profile respect to the fruits, but with more detected phenolics. All fruit pulp extracts exerted antioxidant activity (highest for Fruit 3) and higher α-glucosidase inhibition than acarbose used as standard. Conclusions: This study confirmed the variability of baobab with different origins and indicated Malian species baobab as a promising source of health-promoting substances.

Today, ethno-pharmacology is a very important resource in order to discover new therapies for the current diseases. Moreover, another good justification for the ethno-pharmacological approach is to obtain new, effective, less expensive and simple therapies, limiting at the same time the cost of pharmaceutical research. Two major anti-malarial drugs widely used today, i.e. quinine and artemisinin, came respectively from Peruvian and Chinese ancestral treatments reported in the traditional medicines. In this contest, there is an urgent need for the discovery of new drugs, due to the critical epidemiological situation of this disease and to the growth of resistances. In Mali, malaria and liver diseases remain one of the leading public health problems. Many medicinal plants are often used, in local traditional medicine, for the treatment at the same time of malaria and liver diseases, including hepatic syndromes, jaundice, hepatitis and other hepatic disorders. Moreover, in the local language Bamanan, the word "Sumaya" is used both for malaria and some liver diseases. In addition, we noted that some of the improved traditional phytomedicines produced by the Department of Traditional Medicine are prescribed by modern doctors both for malaria and liver diseases. In this review, pharmacological, toxicological and phytochemical data on Argemone mexicana L. (Papaveraceae), Cochlospermum tinctorium Perr. ex A. Rich (Cochlospermaceae), Combretum micranthum G.Don (Combretaceae), Entada africana Guillet Perr. (Mimosaceae), Erythrina senegalensis A. DC (Fabaceae), Mitragyna inermis (Willd) Kuntze (Rubiaceae), Nauclea latifolia Smith syn. Sarcocephalus latifolius (Smith) Bruce (Rubiaceae), Securidaca longepedunculata Fresen (Polygalaceae), Trichilia emetica Vahl. (Meliaceae), and Vernonia colorata (Willd) Drake (Asteraceae) are reported. Some of the collected data could be used to improve the actual herbal drugs and to propose new phytomedicines for the management of malaria and liver diseases.

BACKGROUND In 2003, a study in Mali showed that 87% of episodes of uncomplicated malaria were first treated at home. We investigated whether treatment-seeking patterns in Mali had changed 10 years later. METHODS In 2013, we repeated the retrospective treatment-outcome study on 400 children with presumed malaria in the same area. RESULTS Most children with reported uncomplicated malaria were still first treated at home (76% [196/258] in 2013 vs 85% in 2003; p=0.006), rather than in modern health centres (20% [52/258] in 2013 vs 12% in 2003; p=0.01). Overall, 58% of children with uncomplicated malaria were treated with herbal medicine alone, a significant increase from 24% 10 years earlier (p<0.001). This was associated with an increase in use of Argemone mexicana decoction from 8% to 26% (p<0.001), with a reported cure or improvement in 100% of cases among those aged >5 years. For severe malaria, first treatment was sought less often from a traditional healer compared with 10 years earlier (4% vs 32%; p<0.001) and more often from a modern health centre (29% vs 17%; p=0.04). CONCLUSIONS Two trends that emerged are that there is a greater use of modern health facilities for treatment of severe malaria, and a greater use of traditional medicine alone for treatment of uncomplicated malaria.

Ethnopharmacological relevance: Protection of intellectual property rights and benefit-sharing are key issues for all ethnopharmacological research. The International Society of Ethnobiology has produced helpful guidelines on access and benefit-sharing which are widely viewed as a "gold standard" but the question remains how best to apply these guidelines in practice. Difficult questions include ownership of traditional knowledge, making appropriate agreements, and how appropriately to share benefits.Materials and methods: We present the case study of the development of an "improved traditional medicine" for malaria in Mali and we report how benefit-sharing was applied in this case.Results: The knowledge about the selected plant came independently from several families and traditional healers. The IPR approach was to recognise that this traditional knowledge belongs to the people of Mali and was used for their benefit in developing a new "improved traditional medicine" (ITM). The traditional healer whose method of preparation was used, and who collaborated in clinical trials, did not request any financial reward but asked for the ITM to be named after him. The most sustainable benefit for the community was sharing the results of which preparation of which medicinal plant seemed to be the most effective for treating malaria. Attempts at providing a health centre and training a health worker for the village did not prove to be sustainable.Conclusions: Respect for intellectual property rights and benefit-sharing are possible even in a context where the knowledge is not owned by a clearly identified person or group of people. The most sustainable benefits are intangible rather than material: namely recognition, improved knowledge about which traditional treatment is the best and how to prepare and take it. (c) 2015 Elsevier Ireland Ltd. All rights reserved.

Nous avons mené en mai 2012 une étude transversale, descriptive à passage unique dans 3 établissements scolaires de la commune urbaine de Sikasso. Cette étude avait pour objectif général d’étudier les connaissances, les attitudes et les pratiques des jeunes lycéens en matière des IST du VIH et du SIDA. Les élèves de sexe féminin étaient prédominants (60,2 %). La moyenne d’âge était de 19,4 ans avec des âges extrêmes de 15 ans et 24 ans. Plus de la moitié (69,2 %) des élèves avaient déjà entendu parler des IST et la prévalence déclarée d’IST et/ou des symptômes associés à la présence d’IST était estimée à 27,0 %. La majorité des élèves, 97,9 %, avait déjà entendu parler du VIH et du Sida, les principales sources d’information de ces élèves étaient : la télévision (93,3 %), la radio (87,3 %) et l’école (84,8 %) et leurs connaissances sur le Sida étaient bonnes. Selon leurs attitudes, 39,1 % des élèves ont déclaré avoir fait le test de dépistage parmi lesquels 97,8 % des garçons et 95,6 % des filles ont retiré leur résultat. La majorité des élèves, 97,1 % des filles et 94,7 % des garçons savaient que le préservatif protège du VIH et du SIDA dont 59,5 % ont déclaré l’avoir utilisé lors des derniers rapports sexuels. Ils étaient 156 soit 54 %, à avoir déjà eu des rapports sexuels dont 22,9 % l’ont eu avec deux partenaires sexuels au cours des 12 derniers mois. Une forte proportion des élèves (64,4 %) a assisté au moins une fois à une séance de sensibilisation sur les IST, le VIH et le SIDA.

Background: Inpatient case fatality from severe malaria remains high in much of sub-Saharan Africa. The majority of these deaths occur within 24 hours of admission, suggesting that pre-hospital management may have an impact on the risk of case fatality.Methods: Prospective cohort study, including questionnaire about pre-hospital treatment, of all 437 patients admitted with severe febrile illness (presumed to be severe malaria) to the paediatric ward in Sikasso Regional Hospital, Mali, in a two-month period.Findings: The case fatality rate was 17.4%. Coma, hypoglycaemia and respiratory distress at admission were associated with significantly higher mortality. In multiple logistic regression models and in a survival analysis to examine pre-admission risk factors for case fatality, the only consistent and significant risk factor was sex. Girls were twice as likely to die as boys (AOR 2.00, 95% CI 1.08-3.70). There was a wide variety of pre-hospital treatments used, both modern and traditional. None had a consistent impact on the risk of death across different analyses. Reported use of traditional treatments was not associated with post-admission outcome.Interpretation: Aside from well-recognised markers of severity, the main risk factor for death in this study was female sex, but this study cannot determine the reason why. Differences in pre-hospital treatments were not associated with case fatality.

L’article presente les experiences d’appui aux femmes herboristes du District de Bamako (Mali) developpees par Aidemet Ong depuis l’annee 2005. Il s’agit de la fourniture de kiosques pour l’exposition ordonnee et la bonne conservation des plantes medicinales, ainsi que d’activites de formation et de suivi. Les resultats des enquetes menees montrent que le revenu mensuel des herboristes qui ont recu les kiosques est superieur de 38% a celui des herboristes sans kiosques. L’analyse des histoires de vie et des propos des femmes herboristes demontre que l’introduction des kiosques a permis d’ameliorer leurs conditions de travail, leurs revenus et la qualite des plantes vendues aux clients, tout en diminuant la pression sur les ressources naturelles. En meme temps, les actions d’appui ont ameliore l’image des herboristes aupres d’elles memes et la perception de l’importance de leur travail aupres des clients, des respectives familles et de la communaute.

The Journal of Alternative and Complementary MedicineVol. 18, No. 3 PhotoessayOpen AccessImproved Traditional Medicines in MaliMerlin Willcox, Rokia Sanogo, Chiaka Diakite, Sergio Giani, Berit Smestad Paulsen, and Drissa DialloMerlin WillcoxDepartment of Primary Health Care, University of Oxford, Oxford, UK.Research Initiative on Traditional Antimalarial Methods, Oxford, UK.Search for more papers by this author, Rokia SanogoDépartement de Médecine Traditionnelle, Institut National de Recherche en Santé Publique, Bamako, Mali.Faculté de Médecine, Pharmacie et Odonto-Stomatologie, Université de Bamako, Mali.Search for more papers by this author, Chiaka DiakiteDépartement de Médecine Traditionnelle, Institut National de Recherche en Santé Publique, Bamako, Mali.Search for more papers by this author, Sergio GianiAidemet ONG, Bamako, Mali.Search for more papers by this author, Berit Smestad PaulsenSchool of Pharmacy, University of Oslo, Oslo, Norway.Search for more papers by this author, and Drissa DialloDépartement de Médecine Traditionnelle, Institut National de Recherche en Santé Publique, Bamako, Mali.Faculté de Médecine, Pharmacie et Odonto-Stomatologie, Université de Bamako, Mali.Search for more papers by this authorPublished Online:15 Mar 2012https://doi.org/10.1089/acm.2011.0640AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Left: The Department for Traditional Medicine, Bamako, Mali. Photo © Merlin Willcox. Right: Médicaments Traditionnels Améliorés for sale on a stall (Bamako, Mali). Photo © Merlin Willcox. Color images available online at www.liebertonline.com/acmIntroductionMali is unusual in enjoying a high level of government support for research and development of traditional medicines. The Department for Traditional Medicine, within the National Institute for Research on Public Health (part of the Ministry of Health), was founded in 1968 (originally as the National Institute of Phytotherapy and Traditional Medicine), and in 2005 moved to new purpose-built premises. Since 1979, one of its aims has been the development of standardized “Médicaments Traditionnels Améliorés” (MTAs, or improved traditional medicines).The “improvement” lies in the pharmacologic evidence of safety and efficacy, the standardized dose and quality control. In order to obtain marketing authorization, a dossier of information on the remedy's safety and efficacy must be submitted to the Commission Nationale d'Autorisation de Mise sur le Marché of the Ministry of Health. Malian regulations categorize traditional medicines as shown in Table 1.1 The requirements for the dossier vary according to the category (Table 2). Most MTAs are of category 2, for which clinical trials are not an absolute requirement.Table 1. Categories of Traditional Medicines in Malian Law1CategoryDescription1Traditional medicine prepared by a traditional health practitioner for an individual patient with fresh or dried raw materials, with a short shelf life2Traditional medicine currently used in the community, prepared in advance, and composed of crude raw materials3Standardized extracts prepared in advance following scientific research4Molecules purified from traditional medicines following scientific researchTable 2. Components of the Brochure for Requesting a Marketing Authorization for a Traditional Herbal Medicine in Mali1SectionDetailed components1. Covering letterAddressed to the Ministry of Health and including the name and address of the manufacturer2. Administrative dossier• Registration document of the manufacturer • Memoranda of understanding between the manufacturer and a research institutiona3. Samples10 samples as sold4. FeesReceipt for registration fees5. Pharmaceutical dossierb• Complete monograph(s) of the component plant(s) • Method and stages of preparation and production • Expert report on Good Manufacturing Practices6. Expert analytical report• Quality control method for raw materials • Results of stability and quality control tests of raw materials and excipients • Method and results of quality control during production • Results of quality control of the finished product • Results of stability tests of the finished product7. Pharmacology and toxicology dossierc• Pharmacodynamic data • Results of acute and subchronic toxicity tests • Literature review of pharmacology and toxicology • Expert report on the tests carried out8. Clinical dossierc• Ethical approval for clinical trials • Clinical trial protocol following standard methods (phase I and II) • Results of clinical trials • Expert report on clinical trials carried out9. Expert report on traditional use• Evidence of long experience of use of the medicine in its current or traditional form (minimum 20 years) • Detailed presentation of known toxicological risks • Risks of incorrect use of the medicine • Risks of physical or psychologic dependenceaFor medicines of categories 3 and 4.bFor medicines of categories 2 and 3.cFor medicines of category 3.Since 1990, MTAs have been included on the Essential Drugs List of Mali, are included in the Malian National Formulary2 alongside conventional drugs, and are distributed through pharmacies. There are currently seven approved MTAs in the formulary2 (Table 3), and more are under development. They are intended to be a safe and effective, but locally produced and less expensive, alternative to imported medicines. This article is a systematic review of the preclinical and clinical literature on the safety and efficacy of these medicines. Voucher specimens of all these plants have been deposited at the herbarium of the Département de Médecine Traditionnelle (Table 3). Monographs for all these plants are available online at: http://portal.ics.trieste.it/MAPs/MedicinalPlants_Country.aspx#MaliTable 3. The Seven Official “Improved Traditional Medicines” in MaliNameConstituent plant(s)Plant partPreparationDoseIndicationContraindicationsVoucher specimen accession numberBalemboCrossopteryx febrifugaFruitSyrup (10% for children, 20% for adults)5 mL qdsDry coughsChildren <6 moNo. 0052. Kangaba (03/11/1973)DysentéralEuphorbia hirtaAerial parts (dried)Decoction10 g boiled in 500 mL water, tds for 3 dAmoebic dysenteryDo not use fresh plantNo. 0952. (03/27/1996)GastrosédalVernonia kotschyanaRoot (dried)Powder, mixed in cold water5 g tds mixed in 70 mL water, 15 min before mealsGastritis, peptic ulcerPregnant women, children <8 yNo. 0929. Sotuba (03/04/1996)HépatisaneCombretum micranthumLeaves (dried)Decoction10 g boiled in 500 mL water, bdIndigestion (especially of fats), nausea, poor appetite, constipationObstructive jaundice, severe liver or renal failure.No. 0031. Dologandori (05/31/1969)Laxa cassiaCassia italicaLeaves (dried)Decoction5–10 g boiled in 500 mL water, at nightConstipationChildren <6 mo, inflammatory bowel diseaseNo. 0963. Blendio. (05/20/1997)MalarialSenna occidentalis (Caesalpinaceae): 62%Leaves (dried)Decoction10 g, boiled in 500 mL water, bd for 4 d, then od for 3 d. Halve dose for children aged 5–12.Malaria, feverChildren <5 yNo. 1525. Point G Lippia chevalieri (Verbenaceae): 32%Leaves (dried) No. 0001. Kita (07/1963) Acmella oleracea (Asteraceae): 6%Flowerheads (dried) No. 2670. Sotuba (09/26/2005)PsorosperminePsorospermum guineenseRootOintment, made with 1% ether extract of root powderApply bd for 2 weeksEczemaNoneNo. 2650. Blendio (09/25/2005)Balembo syrup (Crossopteryx febrifuga)Crossopteryx febrifuga Benth. (Rubiaceae) is a small tree 5–6 m high with small round fruit, which become black when ripe (Fig. 1). They are rich in flavonoids and polysaccharides. The seeds have anti-inflammatory properties.3FIG. 1. Crossopteryx febrifuga (Rubiaceae) black fruits are used to make a cough syrup. Photo © Merlin Willcox. Color images available online at www.liebertonline.com/acmThe fruits are boiled in water to produce a syrup, which was the most effective of several antitussive remedies tested,4 and is nontoxic when given orally.5 There was very low toxicity at the dose of 30 g/kg administrated orally in mice. In the model of cough in guinea pigs provoked by nebulized citric acid, it reduced the number of coughs by 63% at a dose of 250 mg/kg, and by 77% at a dose of 1 g/kg (compared to 76% by codeine at 10 mg/kg). The lower dose of 50 mg/kg was not effective.6 The remedy (at an oral dose of 1 g/kg) also reduced antigen-induced bronchoconstriction in guinea pigs by 54%, compared to a reduction of 78% by disodium cromoglicate (at a dose of 10 mg/kg). However, it had no effect on histamine-induced bronchoconstriction, and aqueous extracts were not active against bacteria that commonly cause respiratory infections.7 A clinical trial in 32 patients with cough showed improvement after 7 days,* and a sedative effect.5† Now Balembo syrup is the most frequently prescribed MTA; it is prescribed by up to 76% of biomedical health workers in Mali, and is also the most widely known by patients.8Dysentéral (Euphorbia hirta)Euphorbia hirta (Euphorbiaceae) is a common pantropical weed (Fig. 2), widely used in many African countries for the treatment of dysentery.9–11E. hirta is active in vitro against several different microorganisms that cause diarrhea or dysentery (Table 4). All studies show a good activity against Entamoeba histolytica, and the whole plant is more active than the leaves alone.12 There are conflicting results for Escherichia coli: One study from India shows good activity,13 whereas two from Africa show minimal or no activity.14,15FIG. 2. Euphorbia hirta (Euphorbiaceae) dried aerial parts are decocted to treat dysentery. Photo © Merlin Willcox. Color images available online at www.liebertonline.com/acmTable 4. In Vitro Activities of Euphorbia hirta Against Microorganisms Causing DiarrheaTarget organismPartFresh or dried?Type of extractActive concentration (g/100 mL)MIC (mg/mL)RefEntamoeba histolyticaWPFreshAqueous decoction20 20 WPDriedAqueous decoction11 20 LFreshAqueous maceration160.25013 WPFreshAqueous maceration200.03113Escherichia coliLDriedEthanol 95%858.016 APDriedEthanol 0.18914Salmonella typhimuriumWPDriedMethanol10 aShigella dysenteriaeFL Methanol0.1.560.2bShigella flexneriFL Methanol0.1.560.1bPolio virusWPDriedEthanol 80%2.5 15Coxsackie virusWPDriedEthanol 80%2.5 15Herpes virusWPDriedEthanol 80%2.5 15aParekh J, Jadeja D, Chanda S. Efficacy of aqueous and methanol extracts of some medicinal plants for potential antibacterial activity. Turk J Biol 2005;29:203–210.bVijaya K, Ananthan S, Nalini R. Antibacterial effect of theaflavin, polyphenon 60 (Camellia sinensis) and Euphorbia hirta on Shigella spp.: A cell culture study. J Ethnopharmacol 1995;49:115–118.MIC, minimum inhibitory concentration; AP, aerial parts; FL, flowers; L, leaves; WP, whole plant.Furthermore, E. hirta contains tannins (such as ellagic acid and gallic acid) and flavonoids (such as quercitin), which have antidiarrheal and antiamoebic activity.12,16 The water extract has spasmolytic activity on guinea-pig ileum9,17 and reduces castor-oil-induced diarrhea in mice.18The pharmacology, chemistry, and toxicology of the plant have been studied extensively.9,19 The aerial parts contain shikimic acid and the roots and sap contain phorbol esters, which are potentially carcinogenic,5,9 although in an experimental model E. hirta ether extracts had almost no tumor-promoting activity compared to other Euphorbia species.20 Roots should not be used, and it is said that aerial parts should be dried, which removes the carcinogenic effect.5,† However, one study found that drying diminishes the in vitro antiamoebic activity.21 Rats fed up to 5% powdered whole plant for up to 97 days in their diet showed no symptoms of poisoning, and no gross pathology on autopsy,9 although hypotensive effects have been found in cats and dogs.17 A daily dose of alcohol extract (corresponding to 3 g/kg of dried plant) was tested in rats for up to 27 days with no observed toxic effects.19 Aqueous extracts produced no toxicity when given orally to rats at doses of up to 30 g/kg.‡Uncontrolled clinical trials of several different extracts have been carried out. The lyophilized decoction (three doses of 10 g) was effective in treating a series of 10 patients with amoebic dysentery in Senegal.9 A tincture of fresh aerial parts (1:2) was tested in a series of 40 cases of acute amoebic dysentery or diarrhea at the Centre Muraz, Bobo-Dioulasso, Burkina Faso.19 Thirty-eight (38) patients were cured with a dose of 10 mL four times daily for 9 days, with normalization of the stools within 2–6 days, and no reported adverse effects.19 A second case series (using the same extract in tablet form, with a daily dose of 7.2 g of dried plant material, for 8 days) resulted in 125 cures out of 150 patients treated.22 In this series, the adverse effects reported were 12 cases of hypotension, two of nausea/vomiting, and one allergic reaction, none of which were severe. An unpublished clinical trial was conducted in Mali of “Dysentéral” treatment (according to the dosage in Table 3). Trophozoites of E. histolytica disappeared from the stool after 2 days, which was equivalent to treatment with metronidazole.5Gastrosédal (Vernonia kotschyana)Vernonia kotschyana Sch. Bip. Ex Walp. (Asteraceae) is a herbaceous plant that grows to a height of about 1 m (Fig. 3). Its thick roots are powdered and used (often mixed with hot water) for indigestion and stomach pains in Mali and Nigeria.23,24 The roots contain steroid glycosides (vernoniosides D1-3 and F1-2)7,25 and different types of polysaccharides such as inulin, pectins, and arabinogalactans, some of which have anti-inflammatory and immunomodulatory properties.24,26FIG. 3. Vernonia kotschyana Sch. Bip. Ex Walp. (Asteraceae) rhizome is effective against indigestion and gastric ulcers. Photo © Merlin Willcox. Color images available online at www.liebertonline.com/acmAqueous extracts are effective at preventing ethanol and stress-induced gastric ulcers in rats, equivalent to 50 mg/kg of ranitidine.27 Two (2) uncontrolled clinical trials have been carried out in patients with gastric ulcers. In the first, 80% (of 47 patients) reported symptomatic improvement.28 In the second, 16 patients were followed up after 30 days of taking V. kotschyana root tablets (6 g daily). Half of the patients had symptomatic improvement, and the ulcers had healed in 6 patients.24‡Hépatisane (Combretum micranthum)Combretum micranthum (Combretaceae) is a small tree, common on the poor soil of the Sahel savannah. Twigs with leaves are commonly sold in markets by the name of kinkéliba.23 Like other Combretum species, it has characteristic four-winged fruit (Fig. 4). Chemical constituents include potassium nitrate, flavonoids (such as vitexin), organic acids, tannins, coumarins, sterols, terpenoids, carbohydrates (inositol, mannitol, sorbitol), and alkaloids (choline, stachydrine).5,23FIG. 4. Combretum micranthum (Combretaceae) leaf decoction is a popular beverage and aids digestion. Photo © Merlin Willcox. Color images available online at www.liebertonline.com/acmIt has a wide variety of medicinal uses in West Africa, particularly as a cholagogue. In 1891, a French doctor in Gambia observed its efficacious use in the treatment of fièvres bilieuses hématuriques (bilious fevers with hematuria).23 The leaves are often used to prepare a refreshing tea, but this is also used for jaundice and hepatitis.11,29 It was added to the French pharmacopoeia in 1937, and to the African Pharmacopoeia in 1985.23 In Mali, patients with nonobstructive jaundice have been treated with Hépatisane and their bilirubin and transaminases have returned to normal within 2–3 weeks of starting the treatment.5 About 50 asymptomatic patients with chronic viral hepatitis B have been treated with Hépatisane in a clinical trial, but there was no clearance of the hepatitis B surface antigen (J. Falquet, personal communication). However, the herbal treatment was well-tolerated, there were no adverse effects, and compliance was good. Further clinical trials are needed to determine whether this treatment helps patients with symptomatic hepatitis, or whether it helps to prevent long-term consequences of chronic viral hepatitis.Laxa Cassia (Senna italica)Senna italica Mill (synonym=Cassia italica, Caesalpinaceae) is a shrub widespread in the dry regions of Africa, and is the local equivalent of senna (which in Europe is made from Cassia senna and Cassia angustifolia). Research has confirmed that its chemical composition is the same as that of C. angustifolia.9 The leaves and fruit are rich in sennosides (anthraquinone glycosides),30 which are broken down in the colon and cecum by the gut flora to the active rhein anthrone. This stimulates peristalsis.31 A common side-effect of overstimulation is colic; this can be reduced by using dry rather than fresh plant material.9Constipation is surprisingly common in Malian villages, attributable to insufficient fiber in the diet (which often consists of little more than maize-meal gruel) and insufficient water intake. As everywhere, it is important to remember that dietary advice (increasing fiber intake, and water intake) is the first-line treatment, and laxatives are a second-line treatment to be used only when absolutely necessary, because of the risk of side-effects. However, it is very sensible for African countries to manufacture their own senna from local plants, rather than to import European senna at a higher price.Malarial“Malarial” was first formulated by Professor Mamadou Koumaré, Professor of Pharmacognosy, former Director of the Department for Traditional Medicine, and President of the Société Malienne de Phytothérapie. It is based on a recipe used in his family, and is now produced as a standardized phytomedicine (Table 3). Senna occidentalis (L.) Link. (synonymous with Cassia occidentalis, Caesalpinaceae) is a pantropical plant (Fig. 5) widely used for the treatment of malaria32 and is active in vitro against malaria parasites.33Lippia chevalieri Mold. (Verbenaceae) is an aromatic herb that is used in West Africa to flavor tea and treat fevers34 (Fig. 6). Acmella oleracea (L.) R.K.Jansen (synonymous with Spilanthes oleracea L., Asteraceae) is a sprawling plant with yellow flowers that have a variety of uses in traditional medicine, including as a local anaesthetic for toothache, and as an antipyretic (Fig. 7). They contain spilanthol, which is effective against Plasmodium falciparum.35 “Malarial” was evaluated against malaria parasites in vitro and in mice. It was not very active in vitro (IC50=470–600 μg/mL) but prolonged the survival of malaria-infected mice by 2–3 days compared to the untreated controls.36 It was also nontoxic to mice.FIG. 5. Cassia occidentalis (Caesalpinaceae) leaves are the major constituent of “Malarial.” Photo © Merlin Willcox. Color images available online at www.liebertonline.com/acmFIG. 6. Lippia chevalieri Mold. (Verbenaceae) leaves are the second constituent of “Malarial” and are mainly used to add a pleasant flavor. Photo © Merlin Willcox. Color images available online at www.liebertonline.com/acmFIG. 7. Spilanthes oleracea (= Acmella oleracea), Asteraceae. Flowerheads are an antimalarial component of “Malarial.” Photo © Merlin Willcox. Color images available online at www.liebertonline.com/acmThree (3) clinical studies were carried out to evaluate the safety and efficacy of Malarial. The first took place in Baguineda in 1984–1985. The second was a randomized controlled trial comparing it to chloroquine.37,38 There were 53 patients included, of whom 36 were randomized to Malarial and 17 to chloroquine. Follow-up to day 21 was completed by 75% of the Malarial group, and 59% of the chloroquine group. Fever clearance was similar in both groups, but parasite clearance was better in the chloroquine group. Malarial was better tolerated than chloroquine. It was felt that the amount of Acmella oleracea (4%) present in this formulation of Malarial was insufficient for a truly effective schizonticidal activity.It was therefore decided to increase the amount of Acmella oleracea in Malarial to 6%, and this was tested in an observational cohort study on patients with uncomplicated malaria.¶ Thirty (30) patients were included, aged 5 years or above, with a temperature of >37.5°C and a parasitemia of >3000/mcl P. falciparum. There was no control group. Parasitemia declined and symptoms improved. Parasitemia at day 7 remained higher in patients aged 8–19 than in older patients. This suggests that patient immunity was playing a role in clearing the parasites.Research in Mali has been ongoing to produce a new MTA for malaria that is more effective than Malarial, which is the least frequently used MTA.9Argemone mexicana decoction has been selected39 and has already undergone clinical trials.40–43 It is anticipated that it will soon be approved as a recommended MTA for malaria.Psorospermine (Psorospermum guineense)Psorospermum guineense Hochr. (synonym=Vismia guineensis (L.) Choisy, Hypericaceae) is a West African shrub (Fig. 8). A decoction of its bark, roots, or branches with leaves is widely used for skin conditions such as eczema, psoriasis,§ scabies, cold sores, and leprosy.23 It contains tannins, anthraquinones, and xanthones. A dichloromethane extract of root bark is active against the intracellular forms of Leishmania major.44FIG. 8. Psorospermum guineense root extract is used to make an ointment for eczema. Photo, printed with permission, by © Dr. Sergio Giani. Color images available online at www.liebertonline.com/acmA double-blind, randomized, controlled clinical trial was conducted in Mali comparing “Psorospermine” (60 patients) with shea butter (50 patients) for the treatment of eczema in patients age 3 years and above.∥ It was applied twice daily after washing with soapy water. After 15 days, the treatment failure rate was 18% in the Psorospermine group, compared to 86% in the shea butter group (p<0.0001). It was more effective for acute than for chronic eczema (12% and 33% of treatment failures, respectively). It was more effective than shea butter for the different symptoms of eczema: pruritus, erythema, vesicles, exudation, and lichenification. Eighty-two percent (82%) of the patients treated with Psorospermine rated it as good or excellent, compared to 14% of patients treated with shea butter.∥ Shea butter, widely used in cosmetics as a moisturizer, salve, or lotion, comes from the nut of the African shea tree (Vitellaria paradoxa), and the English name is derived from the name of the tree in the Malian language Bambara (sisun).DiscussionThe first advantage of “improved phytomedicines” is that they can be developed much faster and more inexpensively than new modern drugs.43 This is because their use, preparation, and safety is already understood in traditional knowledge systems, and so preclinical development can be greatly accelerated. World Health Organization (WHO) guidelines45 state: “If the product has been traditionally used without demonstrated harm, no specific restrictive regulatory action should be undertaken unless new evidence demands a revised risk–benefit assessment.” WHO maintains the position that there is no requirement for preclinical toxicity testing, but rather that evidence of traditional use or recent clinical experience is sufficient.46 This is reflected in the Malian regulations, which only require toxicology and clinical trials for extracts, not for crude traditional preparations (Table 2).The second advantage is that the end product is more widely available and affordable to patients in resource-poor settings than many pharmaceuticals are. MTAs are now considered part of the essential drugs list in Mali.5 In terms of sales, the most successful have been Balembo, Gastrosédal, and Hépatisane, because there is no affordable conventional equivalent for the treatment of jaundice or hepatitis. The least successful has been Malarial, probably in part because it was more expensive than chloroquine, which until recently was the recommended first-line treatment for malaria, and because it was not perceived as effective by most prescribers.9 This emphasizes the need for a new MTA for malaria, which is currently being developed.40–43The third advantage, which is the most important for prescribers and patients, is that they perceive most MTAs to be effective. This was the main reason for choosing to prescribe them as mentioned by 85% of health workers surveyed in Kadiolo district.8 Interestingly, only 38% of prescribers and 29% of patients quoted the lower price as their primary reason for choosing to use MTAs. The most popular MTAs with prescribers were Gastrosédal and Laxa-cassia, and the most popular with patients were Laxa-cassia and Hépatisane.8 Medical students are taught about MTAs during their training, and the Department of Traditional Medicine has conducted training for doctors on the prescription of MTAs. In general it seems that practicing doctors only prescribe MTAs if they have received an additional training session. As in other parts of the world, it seems that some patients and doctors integrate traditional and modern medicines according to their perceived effectiveness.One disadvantage of the production of standardized phytomedicines (as opposed to teaching people to grow and produce their own herbal medicines) is that their distribution is hindered by infrastructure problems, which also affect the distribution of conventional medicines. In the survey in Kadiolo district, MTAs were out of stock on an average of 78 days per year (21% of the time).8 However, the two approaches are not mutually exclusive, and the existence of a government-approved MTA legitimizes the approach of certain nongovernmental organizations to teach people how to grow and produce herbal medicines themselves.10Research on MTAs has been constrained by limited financial resources and the need to strengthen research capacity. In particular, many of the clinical trials have been small, uncontrolled, and have remained unpublished. The Multidisciplinary University Traditional Health Initiative (MUTHI), a recently accepted European Union–funded project, is now attempting to contribute to redress this problem by providing training in both nonclinical and clinical aspects of developing improved phytomedicines. It is hoped that better clinical trials will be conducted and more MTAs will be developed as a result, both in Mali and in other African countries.AcknowledgmentsWe thank Dr. Jacques Falquet for useful comments on this article. Some of the time used to prepare this article was funded by the European Union Research Directorate through the MUTHI project, FP7 Grant Agreement No.: 266005.Disclosure StatementThree of the authors (RS, CD, and DD) are employed by the Département de Médecine Traditionnelle, which produces the Improved Traditional Medicines in Mali. The other authors have no financial conflict of interest.References1 Maiga ZToure OMinisterial Order of 20th September 2005, Determining Ways of Applying for Marketing Authorization of Human and Veterinary Medicines [05-2203/MS-MEP-SG, in French]Bamako, MaliMinistry of Health, Ministry of Farming and Fishing2005.1. Maiga Z, Toure O. Ministerial Order of 20th September 2005, Determining Ways of Applying for Marketing Authorization of Human and Veterinary Medicines [05-2203/MS-MEP-SG, in French]. Bamako, Mali: Ministry of Health, Ministry of Farming and Fishing, 2005. Google Scholar2 National Therapeutic Formulary [in French]BamakoMinistry of Health, Elderly People and Solidarity1998.2. National Therapeutic Formulary [in French]. Bamako: Ministry of Health, Elderly People and Solidarity, 1998. Google Scholar3 Maiga AMalterud KEDiallo DPaulsen BSAntioxidant and 15-lipoxygenase inhibitory activities of the Malian medicinal plants Diospyros abyssinica (Hiern) F. White (Ebenaceae), Lannea velutina A. Rich (Anacardiaceae) and Crossopteryx febrifuga (Afzel) Benth. (Rubiaceae)J Ethnopharmacol2006104132137.3. Maiga A, Malterud KE, Diallo D, Paulsen BS. Antioxidant and 15-lipoxygenase inhibitory activities of the Malian medicinal plants Diospyros abyssinica (Hiern) F. White (Ebenaceae), Lannea velutina A. Rich (Anacardiaceae) and Crossopteryx febrifuga (Afzel) Benth. (Rubiaceae). J Ethnopharmacol 2006;104:132–137. Crossref, Medline, Google Scholar4 Occhiuto FSanogo RGermano MPet al.Effects of some Malian medicinal plants on the respiratory tract of guinea-pigsJ Pharmacy Pharmacol19995112991303.4. Occhiuto F, Sanogo R, Germano MP, et al. Effects of some Malian medicinal plants on the respiratory tract of guinea-pigs. J Pharmacy Pharmacol 1999;51:1299–1303. Crossref, Medline, Google Scholar5 Diallo DPaulsen BSHveem BProducts of traditional medicineBerge GDiallo DHveem BWild Plants of the Malian Sahel [in French]ParisEditions Karthala2005135141.5. Diallo D, Paulsen BS, Hveem B. Products of traditional medicine. In: Berge G, Diallo D, Hveem B, eds. Wild Plants of the Malian Sahel [in French]. Paris: Editions Karthala, 2005:135–141. Google Scholar6 Sutovska MFranova SPriseznakova Let al.Antitussive activity of polysaccharides isolated from the Malian medicinal plantsInt J Biol Macromol200944236239.6. Sutovska M, Franova S, Priseznakova L, et al. Antitussive activity of polysaccharides isolated from the Malian medicinal plants. Int J Biol Macromol 2009;44:236–239. Crossref, Medline, Google Scholar7 Sanogo RGermano MPde Tommasi Net al.Vernoniosides and an androstane glycoside from Vernonia kotschyanaPhytochemistry1998477378.7. Sanogo R, Germano MP, de Tommasi N, et al. Vernoniosides and an androstane glycoside from Vernonia kotschyana. Phytochemistry 1998;47:73–78. Crossref, Google Scholar8 Diallo DDiakité CDiawara Aet al.Study of the consumption of the improved traditional phytomedicines in the he

Argemone mexicana (AM), a validated herbal medicine for uncomplicated malaria, seems to prevent severe malaria without completely clearing parasites in most patients. This study, in a high transmission area of South Mali, explores whether residual parasitaemia at day 28 was associated with subsequent malaria episodes and/or anaemia. Three hundred and one patients were randomly assigned to AM or artesunate/amodiaquine as first line treatment, of whom 294 were followed up beyond the standard 28 days, to 84 days. From day 29 to day 84, there were no significant differences between treatment groups in new clinical episodes of uncomplicated malaria (0.33 vs 0.31 episodes/patient), severe malaria (< 6% per month of patients aged ≤ 5 years) or moderate anaemia (hematocrit < 24%: 1.1% in both groups at day 84). Total parasite clearance at day 28 was not correlated with incidence of uncomplicated or severe malaria or of moderate anaemia over the subsequent two months. Total parasite clearance at day 28 was not clinically important in the context of high transmission. If this finding can be confirmed, some antimalarials which are clinically effective but do not completely clear parasites could nevertheless be appropriate in high transmission areas. Such a policy could be tested as a way to delay resistance to artemisinin combination therapies.

Reflecting on their experiences in Mali, the authors argue that the action-research methodology (AR) is particularly suited to promoting traditional medicines, for three main reasons: systemic approach, flexibility and stakeholder participation. The aim of AR is also the creation and the appropriation of knowledge by local actors: it is not the acquisition or the transmission of knowledge, but the mastering of the process of knowledge creation. Thus, participation in AR is also formative for all participants, including researchers. The authors also underline the importance of dynamic exchange and intercultural communication, gender analysis and the empowerment of local actors. The use of the methodologies and approaches illustrated has achieved some positive results in various fields, such as: promoting good care during pregnancy and safe delivery, traditional treatment of trauma and malaria, and also strengthening of local health systems, safeguarding of biodiversity and improving the work of herbalists. ----- Full text available in French only. To view, please select Francais in the language box.

INTRODUCTION : An estimated 300 to 500 million clinical cases of malaria occur each year worldwide, 90% in Africa, mostly among young children. In Cote d\u0027Ivoire, malaria is 46.03% of disease states and 62.44% of hospital admissions. In children under 5 years, it is 42.67% of the reasons for consultation and 59.68% of hospital admissions. In pregnant women, it represents 22.91% of disease states and 36.07% of hospital admissions. In Africa, traditional medicine is the first resort for the vast majority of people, because of its accessibility both geographically, economically and culturally. However, some modern practitioners show an attitude of distrust of traditional medicine and its players, calling them irrational. This work had set out to assess knowledge, attitudes and practices of traditional healers in the uncomplicated and complicated in the context of collaboration between traditional and modern medicine for the optimal management of critical cases. MATERIALS AND METHOD : The study focused on traditional healers practicing in the city of Abidjan. The study was conducted using individual interviews over a period of 30 days. The interviews were conducted in local languages, with the assistance, if necessary, translators. For data collection, we used a questionnaire containing four items: the socio-demographic characteristics of traditional healers, their knowledge on malaria, diagnostic practices and traditional therapies. RESULTS : Of the 60 healers and included in the study, only six were women (10%), a sex-ratio of a woman to 9 men. 66.7% of respondents traditional healers are herbalists and 25% of naturopaths.Only 8.3% were spiritualists. The etiology of malaria most commonly cited by the traditional healers were mosquito bites (16.7%), food (1.7%), solar (1.7%) and fatigue (1.7%) . 25% of traditional healers are associated with mosquitoes, sun and fatigue. Symptomatology most cited were fever (100%), dark urine (86%), the yellow or pale conjunctiva (80%), vomiting (71.7%), nausea (58.3%) and abdominal pain (48.3%). Traditional healers recognized three types of malaria: the white shape, form yellow / red and the black form. Traditional healers malarious patients surveyed were receiving both first (58.3%) than second-line (41.7%). 78.3% of them practiced an interview and physical examination of theirpatients before the diagnosis. In 13.3% of cases they were divinatory consultation. Medications used to treat malaria were herbal in 95% of cases. The main sign of healing was the lack of fever (58.3%). 90%of traditional healers interviewed referring cases of malaria black (severe malaria). This reference is made to modern health facilities (90.2%). 68.3% of respondents practiced traditional healers of malaria prophylaxis among pregnant women and children under 5 years.CONCLUSION : A description of clinical malaria by traditional practitioners in health is not very far from that of modern medicine. Nevertheless, the logics of our respondents are etiological more complex and linked to their cultural context. The management of cases is made from medicinal plants in treatment failure patients are usually referred to modern health facilities. The involvement of traditional healers in the detection and quick reference risk cases can contribute to reducing child mortality due to severe malaria.

INTRODUCTION:An estimated 300 to 500 million clinical cases of malaria occur each year worldwide, 90% in Africa, mostly among young children. In Cote d'Ivoire, malaria is 46.03% of disease states and 62.44% of hospital admissions. In children under 5 years, it is 42.67% of the reasons for consultation and 59.68% of hospital admissions. In pregnant women, it represents 22.91% of disease states and 36.07% of hospital admissions. In Africa, traditional medicine is the first resort for the vast majority of people, because of its accessibility both geographically, economically and culturally. However, some modern practitioners show an attitude of distrust of traditional medicine and its players, calling them irrational. This work had set out to assess knowledge, attitudes and practices of traditional healers in the uncomplicated and complicated in the context of collaboration between traditional and modern medicine for the optimal management of critical cases.MATERIALS AND METHOD:The study focused on traditional healers practicing in the city of Abidjan. The study was conducted using individual interviews over a period of 30 days. The interviews were conducted in local languages, with the assistance, if necessary, translators. For data collection, we used a questionnaire containing four items: the socio-demographic characteristics of traditional healers, their knowledge on malaria, diagnostic practices and traditional therapies.RESULTS:Of the 60 healers and included in the study, only six were women (10%), a sex-ratio of a woman to 9 men. 66.7% of respondents traditional healers are herbalists and 25% of naturopaths.Only 8.3% were spiritualists. The etiology of malaria most commonly cited by the traditional healers were mosquito bites (16.7%), food (1.7%), solar (1.7%) and fatigue (1.7%) . 25% of traditional healers are associated with mosquitoes, sun and fatigue. Symptomatology most cited were fever (100%), dark urine (86%), the yellow or pale conjunctiva (80%), vomiting (71.7%), nausea (58.3%) and abdominal pain (48.3%). Traditional healers recognized three types of malaria: the white shape, form yellow / red and the black form. Traditional healers malarious patients surveyed were receiving both first (58.3%) than second-line (41.7%). 78.3% of them practiced an interview and physical examination of theirpatients before the diagnosis. In 13.3% of cases they were divinatory consultation. Medications used to treat malaria were herbal in 95% of cases. The main sign of healing was the lack of fever (58.3%). 90%of traditional healers interviewed referring cases of malaria black (severe malaria). This reference is made to modern health facilities (90.2%). 68.3% of respondents practiced traditional healers of malaria prophylaxis among pregnant women and children under 5 years.CONCLUSION:A description of clinical malaria by traditional practitioners in health is not very far from that of modern medicine. Nevertheless, the logics of our respondents are etiological more complex and linked to their cultural context. The management of cases is made from medicinal plants in treatment failure patients are usually referred to modern health facilities. The involvement of traditional healers in the detection and quick reference risk cases can contribute to reducing child mortality due to severe malaria.

GOALS In the frame of the project "Bringing the healthcare near to the people of Municipality of Zegoua" one goal was the strengthening of SLIS and its adaptation to the context of decentralization. METHODOLOGY The research included the decentralized collection and analysis of health data (modern and traditional) and the presentation of key indicators in graphical form to local authorities, to support decision making. RESULTS The analysis of data from 2006-2008 found: the increase in Curative Consultation from 0.24 to 0.40; achieving universal coverage in Pre-Natal Consultations and Assisted Deliveries, 86.12% coverage in Post-Natal Consultations. For 2008, the evolution of key indicators for month was presented to local authorities and the data were also disaggregated by village. The analysis of financial data allowed to draw up the balance of the Zégoua Polycentric CHCs, and to monitor the capital of essential drugs. About Traditional Medicine, it was identified one traditional healer for 236 inhabitants. The average was 277 patients per month. The first cause of consultation was malaria. The availability of essential information presented in an understandable form has enabled local authorities to identify and locate health problems, and to take timely targeted decisions. CONCLUSION These results demonstrate the importance of strengthening the SLIS and of its adaptation to the context of decentralization, as part of the consolidation of local health systems.

BACKGROUND:Over 1200 plant species are reported in ethnobotanical studies for the treatment of malaria and fevers, so it is important to prioritize plants for further development of anti-malarials.METHODS:The "RITAM score" was designed to combine information from systematic literature searches of published ethnobotanical studies and laboratory pharmacological studies of efficacy and safety, in order to prioritize plants for further research. It was evaluated by correlating it with the results of clinical trials.RESULTS AND DISCUSSION:The laboratory efficacy score correlated with clinical parasite clearance (rs=0.7). The ethnobotanical component correlated weakly with clinical symptom clearance but not with parasite clearance. The safety component was difficult to validate as all plants entering clinical trials were generally considered safe, so there was no clinical data on toxic plants.CONCLUSION:The RITAM score (especially the efficacy and safety components) can be used as part of the selection process for prioritising plants for further research as anti-malarial drug candidates. The validation in this study was limited by the very small number of available clinical studies, and the heterogeneity of patients included.

A “reverse pharmacology” approach to developing an anti-malarial phytomedicine was designed and implemented in Mali, resulting in a new standardized herbal anti-malarial after six years of research. The first step was to select a remedy for development, through a retrospective treatment-outcome study. The second step was a dose-escalating clinical trial that showed a dose-response phenomenon and helped select the safest and most efficacious dose. The third step was a randomized controlled trial to compare the phytomedicine to the standard first-line treatment. The last step was to identify active compounds which can be used as markers for standardization and quality control. This example of “reverse pharmacology” shows that a standardized phytomedicine can be developed faster and more cheaply than conventional drugs. Even if both approaches are not fully comparable, their efficiency in terms of public health and their complementarity should be thoroughly considered.

The study, which received the support of the Development and Co-operation Management of the Swiss Confederation in the frame of the Socio-Sanitary Support Program Mali-Switzerland, proceeded from February to March 2004. The goal was to evaluate the impact of a workshop of formation of the prescribers on the Improved Traditional Phytomedicines (ITP), carried out in October 2001, on the consumption of the ITP in the medical structures of the District of Kadiolo. The study required the data-gathering of consumption, starting from the cards of stock of the years 2001, 2002 and 2003 of the Distributor Warehouse of the Reference Health Center and of the Pharmacies of the Community Health Centers. To evaluate the appreciation of the ITP, the investigations were carried out near the prescribers and the users. The overall consumption of ITP in CSRéf and 16 CSCom of the District knew a progressive increase, while passing from 2 565 480 F CFA in 2001 to 4 307 760 F CFA in 2003. The consumption of ITP during the year 2003 was of 27.83 F CFA per capita. The ITP in general were well appreciated by the prescribers and the consumers. Various projections of the consumption data recorded in Kadiolo allowed considering the potential market of the ITP currently available in Mali with a value ranging between 414 and 560 millions of F CFA.