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

Abstract

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.

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

“…6 Two strategies for HMM were compared in a randomised controlled trial (RCT): AM as first line treatment with artesunate/amodiaquine (As/Aq) as second line ('AM group'); or the standard As/Aq as first line with another artemisinin combination therapy (ACT), arthemeter/lumefantrine, as second line ('ACT group'). 7 Following the usual practice of assessing antimalarial treatments by outcome in the 28 days after diagnosis, we found that progress to severe malaria was 1.9% in children aged ≤5 years in both groups, and 0% among those aged >5years old, so that the incidence of severe malaria was kept to a lower level than reported in comparable studies of HMM. 8 However the AM and ACT groups were very different in terms of parasite clearance.…”

“…7 In summary, incidence of severe malaria was under 2.5% in both groups. Most of these cases involved severe anaemia.…”

“…7 In summary, sample size was computed in order to detect a difference of 15% assuming an adequate clinical response rate of at least 85% with an ACT (␣ = 0.05, 1-␤ = 0.80, two-tailed test). Patients were randomly assigned to two groups, AM or ACT, using a computergenerated random number table and a 2:1 randomisation ratio with blocks of six stratified for age (<1 year, 1-5 years, >5 years).…”

“…7 All blood films taken on d 0, d 7, d 28 and the day of a presumed new episode of malaria were read independently by two microscopists. Parasites were counted per 200 leucocytes (and per 500 leucocytes if there were fewer than 10 parasites per 200 leucocytes).…”

"Test and treat" or presumptive treatment for malaria in high transmission situations? A reflection on the latest WHO guidelines

“…Parasites which already have resistance to these drugs may be selected for, but it is improbable that any new resistant mutations would develop in this context because the biomass of parasites in the inoculum is low. A strategy for preventing resistance could be to keep ACTs for patients at highest risk of severe malaria (non-immune patients) and to use other medicines for semi-immune patients (aged 5 years and older, in high-transmission areas), who will improve with other treatments[32]. …”