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Published on: October 11, 2019
[Intrarectal administration of quinine: an early treatment for severe malaria in children?]
H Barennes1, D Kailou, E Pussard
1Centre Muraz, BP 153, Bobo Dioulasso, Burkina Faso. barenness@fasonet.bf
Insights
Intrarectal quinine (QIR) offers a painless and effective early treatment for severe childhood malaria, particularly in rural Africa where access to healthcare is limited. This method shows comparable efficacy to intravenous and intramuscular routes, potentially reducing mortality and side effects.
Area of Science:
- Tropical Medicine
- Pediatric Infectious Diseases
- Pharmacology
Background:
- Severe malaria causes significant childhood mortality in Africa, exacerbated by limited healthcare access in rural areas.
- Intrarectal administration presents a non-aggressive, painless, and easily applicable treatment option for children.
- Previous research established the pharmacokinetic profile, optimal dosage, and clinical efficacy of intrarectal quinine (QIR).
Purpose of the Study:
- To evaluate the clinical efficacy and safety of intrarectal quinine (QIR) compared to standard treatments for severe and cerebral malaria in children.
- To assess QIR as a viable alternative treatment, especially in resource-limited settings with poor healthcare accessibility.
Main Methods:
- Two open clinical trials conducted in Niger (1994-1996) involving children aged 2-15 years.
- QIR was compared against intravenous quinine infusion in cerebral malaria (n=76) and intramuscular quinine in severe malaria (n=57).
- Specific QIR dosing regimens were used: 20 mg/kg followed by 15 mg/kg every 8 hours for cerebral malaria, and 30 mg/kg followed by 20 mg/kg every 12 hours for severe malaria.
Main Results:
- In cerebral malaria, mortality rates were similar between QIR (4/76) and IV infusion (9/76) groups (P > 0.05), with comparable clinical recovery times.
- In severe malaria, QIR demonstrated significantly lower mortality (0%) compared to intramuscular quinine (7.6%) (P > 0.005), with similar clinical outcomes.
- QIR achieved comparable residual blood quinine concentrations to intravenous administration, indicating effective absorption and therapeutic levels.
Conclusions:
- Intrarectal quinine (QIR) is an effective and well-tolerated treatment for severe malaria in children, particularly when intravenous access is challenging.
- The simplicity and efficacy of QIR offer a promising strategy to reduce childhood malaria mortality linked to treatment delays and to mitigate side effects associated with intramuscular quinine administration.
- QIR represents a valuable therapeutic option for managing severe malaria in resource-limited African settings, improving patient outcomes and accessibility.
Abstract:
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.
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