Medicinal Plants Used in Mali for the Treatment of Malaria and Liver Diseases.

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.

Intellectual property rights, benefit-sharing and development of "improved traditional medicines": A new approach.

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.

Home treatments alone or mixed with modern treatments for malaria in Finkolo AC, South Mali: reported use, outcomes and changes over 10 years.

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.

Do ethnobotanical and laboratory data predict clinical safety and efficacy of anti-malarial plants?

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 for developing an anti-malarial phytomedicine.

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.

Is parasite clearance clinically important after malaria treatment in a high transmission area? A 3-month follow-up of home-based management with herbal medicine or ACT.

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.

[Decentralization of healthcare and analysis of health data: the experience of the community of Zegoua, Mali]. / Decentralisation De La Sante Et Systeme Local D'Information Sanitaire : L'Experience De La Commune De Zegoua (District De Kadiolo, Region De Sikasso, Mali).

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.

Argemone mexicana decoction versus artesunate-amodiaquine for the management of malaria in Mali: policy and public-health implications.

A classic way of delaying drug resistance is to use an alternative when possible. We tested the malaria treatment Argemone mexicana decoction (AM), a validated self-prepared traditional medicine made with one widely available plant and safe across wide dose variations. In an attempt to reflect the real situation in the home-based management of malaria in a remote Malian village, 301 patients with presumed uncomplicated malaria (median age 5 years) were randomly assigned to receive AM or artesunate-amodiaquine [artemisinin combination therapy (ACT)] as first-line treatment. Both treatments were well tolerated. Over 28 days, second-line treatment was not required for 89% (95% CI 84.1-93.2) of patients on AM, versus 95% (95% CI 88.8-98.3) on ACT. Deterioration to severe malaria was 1.9% in both groups in children aged 5 years) and 0% had coma/convulsions. AM, now government-approved in Mali, could be tested as a first-line complement to standard modern drugs in high-transmission areas, in order to reduce the drug pressure for development of resistance to ACT, in the management of malaria. In view of the low rate of severe malaria and good tolerability, AM may also constitute a first-aid treatment when access to other antimalarials is delayed.

[Study of the consumption of the Improved Traditional Phytomedicines in the health district of Kadiolo (Region of Sikasso, Mali)]. / Etude de la consommation des Medicaments Traditionnels Ameliores dans le district sanitaire de Kadiolo (Region de Sikasso, Mali).

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.

[Knowledge of traditional healers on malaria in Kendi (Bandiagara) and Finkolo (Sikasso) in Mali ]. / La prise en charge du paludisme par les therapeutes traditionnels dans les aires de sante de Kendie (Bandiagara) et de Finkolo (Sikasso) au Mali.

The survey has been carried out in the context of the project "Traditional Practices and Primary Health Care", developed by the Traditional Medicine Department (DMT) of the INRSP and the Swiss Ngo Antenna Technologies, with the support of Aidemet Ngo. The objective was to evaluate the knowledge, attitudes and practices of traditional healers on uncomplicated and severe malaria, in the perspective of collaboration between traditional and modern medicine for the optimal care of the critical cases. The investigation has been conducted from January to February 2003 in the health areas of Kendié (Bandiagara District, Mopti Region) and Finkolo (Sikasso District and Region). The interviews concerned in total 79 traditional healers, 9 of which were women. The survey showed that the traditional healers have a good knowledge of the symptomatology of uncomplicated and severe malaria, and their diagnosis corresponds with that of the health workers who do not have access to laboratory analyses. On the other hand, the traditional etiology doesn't always correspond with the modern one, even if the traditional healers mention, among the causes of malaria, the mosquito bites. Most treatments were based on plant substances. We identified 66 medicinal species in total. The majority of them had already been studied for anti-plasmodial activity. We therefore investigated 8 of these plants, which had not previously been thoroughly studied. Extracts of different parts of these plants were tested on standard chloroquine-resistant strains of Plasmodium falciparum; the most active plants were Argemone mexicana, Securinega virosa, Spondias mombin and Opilia celtidifolia, with IC50 ranging from 1.00 to 4.01 microg/ml.

Malaria treatment in remote areas of Mali: use of modern and traditional medicines, patient outcome.

Use of official health services often remains low despite great efforts to improve quality of care. Are informal treatments responsible for keeping a number of patients away from standard care, and if so, why? Through a questionnaire survey with proportional cluster samples, we studied the case histories of 952 children in Bandiagara and Sikasso areas of Mali. Most children with reported uncomplicated malaria were first treated at home (87%) with modern medicines alone (40%), a mixture of modern and traditional treatments (33%), or traditional treatment alone (27%). For severe episodes (224 cases), a traditional treatment alone was used in 50% of the cases. Clinical recovery after uncomplicated malaria was above 98% with any type of treatment. For presumed severe malaria, the global mortality rate was 17%; it was not correlated with the type of treatment used (traditional or modern, at home or elsewhere). In the study areas, informal treatments divert a high proportion of patients away from official health services. Patients' experience that outcome after standard therapeutic itineraries is not better than after alternative care may help to explain low use of official health services. We need to study whether some traditional treatments available in remote villages should be considered real, recommendable first aid.