We detected no difference in the effect on parasites and clinical illness for intrarectal quinine, but most trials were small. Pain may be less with intrarectal proprietary, buffered quinine preparations (made less acidic by adjustment of the pH to 4.5). Further larger trials in patients with severe malaria and in adults are required before the intrarectal route can be recommended.
Safety and efficacy of rectal compared with intramuscular quinine for the early treatment of moderately severe malaria in children: randomised clinical trial.
To compare the safety and efficacy of quinine given by the rectal route with quinine given by the intramuscular route in children with moderately severe Plasmodium falciparum malaria.
                Randomised, open, clinical trial.
                Health centre in Burkina Faso.
                898 children with moderately severe P falciparum malaria who were unable to take oral treatment.
                Rectal quinine (20 mg/kg diluted to 30 mg/ml in water solution) or intramuscular quinine (12.5 mg/kg) every 12 hours until oral quinine could be taken.
                Primary safety outcome was the presence of blood in stools and secondary safety outcome was diarrhoea. Primary efficacy outcome was early treatment failure and secondary efficacy outcomes were late clinical and parasitological failures, fever clearance time, and time to oral intake.
                Blood in stools and diarrhoea were more common in children given quinine by the rectal route than by the intramuscular route (blood in stools: 5% v 1%, absolute difference 3.9%, 95% confidence interval 1.8% to 6.1%; diarrhoea: 5% v 1%, 3.5%, 1.3% to 5.7%). On anoscopy, inflammatory lesions (9/248, 3%) were associated with bloody striations in stools. Side effects of rectal quinine were rare and transitory. Local pain (90%), inflammation (79%), and transient impairment of mobility (15%) were observed with intramuscular quinine. Early treatment failure was higher in the rectal group (6% v 3%, absolute difference 3.0%, 95% confidence interval 0.2% to 5.9%). All except two children in each group had negative blood slide results at day 5. Fever recurrence at day 7 was higher in the intramuscular group (37/375 v 18/395, absolute difference 5.3%, 1.6% to 8.9%). Other efficacy outcomes (late clinical failure, late parasitological failure, fever clearance time, time to starting oral intake and rate of deterioration to severe malaria) did not differ.
                Quinine given by the rectal route has an acceptable safety profile and could be used in the early management of moderately severe malaria in children in sub-Saharan Africa, halting progression to severe disease.