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.
Summary A prospective, dose-escalating, quasi-experimental clinical trial was conducted with a traditional healer using a decoction of Argemone mexicana for the treatment of malaria in Mali. The remedy was prescribed in three regimens: once daily for 3 days (Group A; n = 23); twice daily for 7 days (Group B; n = 40); and four times daily for the first 4 days followed by twice daily for 3 days (Group C; n = 17). Thus, 80 patients were included, of whom 80% were aged <5 years and 25% were aged <1 year. All presented to the traditional healer with symptoms of malaria and had a Plasmodium falciparum parasitaemia >2000/l but no signs of severe malaria. The proportions of adequate clinical response (ACR) at Day 14 were 35%, 73% and 65% in Groups A, B and C, respectively (P = 0.011). At Day 14, overall proportions of ACR were lower in children aged <1 year (45%) and higher in patients aged >5 years (81%) (P = 0.027). Very few patients had complete parasite clearance, but at Day 14, 67% of patients with ACR had a parasitaemia <2000/l. No patient needed referral for severe disease. Only minor side effects were observed. Further research should determine whether this local resource could represent a first-aid home treatment in remote areas.
a b s t r a c tA 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 (there were no cases in patients aged >5 years) and 0% had coma/convulsions. AM, now government-approved in Mali, could be tested as a firstline 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.
Summary 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.
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