Randomized trial evaluating the efficacy and tolerability of oral quinine, 16 mg/kg/day versus 24 mg/kg/day, in the treatment of uncomplicated Plasmodium falciparum malaria in adults

In sub-Saharan Africa, given the high cost of drugs and the resurgence of parasite resistance, new credible therapeutic strategies must be defined. With this in mind, the African Quin study, conducted in 13 countries among 500 practitioners on 3981 patients, showed that in adults with uncomplicated malaria quinine produces spectacular clinical and parasitological efficacy at a daily dosage of 2 tablets of 250 mg of quinine, corresponding to 16 mg/kg/day of quinine base. However, these results were called into question because of numerous methodological problems. OBJECTIVE: The objective of our study was to evaluate, in adults with uncomplicated P. falciparum malaria, the efficacy, tolerability and adherence of the 16 mg/kg/day dosage versus 24 mg/kg/day. METHODS: A randomized, multicentre, comparative trial of 16 mg/kg/day versus 24 mg/kg/day was conducted in adult patients treated for 5 days. The primary objective was to seek an equivalent cure rate between the two arms at D7, D14 and D28. No PCR genotyping was done, so it is difficult to distinguish relapses or recrudescences from reinfections. Statistical analysis was conducted by intention to treat and per protocol. The equivalence test was based on the 95% confidence interval of the difference in patients with success at the end of treatment. RESULTS: The initial study population was 320 patients, with a mean age of 28 years and a range of 18 to 67 years. The two patient populations were comparable before the start of treatment with regard to demographic characteristics, clinical signs, parasitaemia and laboratory abnormalities. At the end of treatment, the clinical success rate was 96% for 16 mg/kg/d versus 97% for 24 mg/kg/d in the ITT analysis and 99% for 16 mg/kg/d versus 99% for 24 mg/kg/d in the PP analysis, statistically similar rates. On the other hand, tolerability was better for the 16 mg/kg/d regimen (60% vs 50%; p=1). CONCLUSION: This comparative study shows equivalent efficacy of the two oral quinine dosages. The results suggest that in adults living in endemic areas, by contributing to treatment adherence, the 16 mg/kg dosage can be considered as an alternative in the treatment of uncomplicated P. falciparum malaria.