[Intrarectal administration of quinine: an early treatment for severe malaria in children?]. / Administration intrarectale de la quinine: un traitement précoce du paludisme grave de l'enfant?

Delay for treatment of severe malaria is the cause of an important childhood mortality in Africa especially in rural zone when health facilities and accessibility are scarce. Intrarectal treatment is of particular interest in children as a non aggressive, painless and easy treatment. It can be used as early treatment and could decrease the lethality of severe malaria. We recently showed the kinetic profile, the optimal regimen and the clinical efficacy of intrarectal quinine (QIR) using Quinimax (Sanofi, Gentilly France) 20 mg/kg in solution with 2 ml of water. From 1994 to 1996 two open clinical trials were performed in Niger in children (2-15 years). QIR was compared with intraveinous infusion in cerebral malaria (n = 76) and with intramuscular quinine in severe malaria (n = 57). A three daily QIR administration (20 mg/kg followed by 15 mg/kg/8 h) was used in cerebral malaria; a two daily administration in severe malaria (30 mg/kg followed by 20 mg/kg/12 h). Symptomatic treatment was associated for hyperthermia, hypoglycemia, anemia and seizures. Results. In the cerebral malaria study 58 children presented a Blantyre coma score below 3. Four children in the IR group and 9 children in the infusion group died (P > 0.05). Evolution was similar in both treatment groups: temperature clearance (< 37.5 degrees C) 39.0 +/- 15.2 h and 37.1 +/- 16.5 h; return to consciousness 34.6 +/- 12.8 h and 33.0 +/- 14.1 h; decrease to 50% of the initial parasites count: 15.5 +/- 11.5 h and 13.8 +/- 10.0 h. Residual blood quinine concentrations at 48 hours were similar 7.4 +/- 3.7 mg/l and 7.2 +/- 2.9 mg/l. In the severe malaria study, the mortality was 0 and 7.6% in the QIR and IM group respectively (P > 0.005). Evolution was similar in both treatment groups: temperature clearance (< 37.5 degrees C) 38.7 +/- 22.8 h and 38.6 +/- 22.2 h; return to consciousness 26.8 +/- 13.9 h and 27.6 +/- 9.9 h for the 16 children in coma. The evolution under QIR treatment was also similar with that described with the other quinine routes. QIR allows an efficious treatment particularly when correct infusion cannot be performed. The efficacy, the simplicity and the good tolerance of QIR are of major concern to decrease the mortality of severe malaria due to delay for treatment and to decrease the side-effects due to intramuscular administrations of quinine in Africa.

An open randomized clinical study of intrarectal versus infused Quinimax for the treatment of childhood cerebral malaria in Niger.

The intrarectal route has been shown to be an alternative to parenteral therapy for the treatment of acute uncomplicated malaria. We conducted an open randomized clinical study of intrarectal Quinimax (a Cinchona alkaloids association) (20 mg/kg, then 15 mg/kg every 8 h) vs. intravenous Quinimax (8 mg/ kg infused over 4 h every 8 h) for 2 d in 76 children (39 in the intrarectal and 37 in the infusion groups) with cerebral falciparum malaria in Niger. This treatment was followed by oral chloroquine (10 mg/kg/d for 3 d). The primary end points of the study were fatal outcome and coma recovery time. In the intrarectal group, 35 children were cured (90%) and 4 died. In the infused group, 28 were cured (76%) and 9 died; mean coma recovery times were 34.6 h (SD = 12.8) and 33.0 h (SD = 14.1) for the intrarectal and infused groups, respectively. None of the differences was significant. Both treatments were well tolerated and no anal irritation was observed with intrarectal Quinimax. These findings suggest that intrarectal Quinimax can be an alternative to intravenous administration for rapid onset childhood cerebral malaria in the rural tropics, where the safety of parenteral administration cannot be guaranteed.