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Life-saving rectal artesunate for complicated malaria in children
Krisana Pengsaa1, Chukiat Sirivichayakul, Kesara Na-Bangchang
1Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Rd, Bangkok 10400, Thailand. tmkps@mahidol.ac.th
Insights
Rectal artesunate effectively treats cerebral malaria in Thai children. This formulation rapidly reduced parasite levels and showed no recurrence, warranting further study for optimized malaria treatment.
Area of Science:
- Tropical Medicine
- Pharmacology
- Pediatric Infectious Diseases
Background:
- Cerebral/complicated falciparum malaria poses a significant threat to children.
- Effective and accessible treatment options are crucial, especially in multidrug-resistant areas.
- Rectal drug administration offers an alternative route when oral intake is not feasible.
Purpose of the Study:
- To evaluate the effectiveness of two rectal artesunate regimens in treating pediatric cerebral/complicated falciparum malaria.
- To assess the safety and tolerability of rectal artesunate in this patient population.
- To explore the pharmacokinetic profile of rectal artesunate and its active metabolite.
Main Methods:
- A study involving 13 Thai children diagnosed with cerebral/complicated falciparum malaria.
- Administration of rectal artesunate at varying initial doses (40 mg/kg or 20 mg/kg) over 24 hours, followed by maintenance doses.
- Concomitant oral mefloquine administration at 72 hours post-initial artesunate dose.
- Monitoring of clinical recovery (consciousness), parasitemia reduction, and plasma drug concentrations.
Main Results:
- Three children with cerebral malaria regained consciousness within 20 hours of rectal artesunate administration.
- Median time for 90% reduction in parasitemia (P90) was 11.2 hours across all patients.
- No recrudescence of malaria was observed during the 28-day follow-up period.
- Pharmacokinetic analysis in two patients indicated rapid absorption and adequate plasma levels of artesunate and dihydroartemisinin.
Conclusions:
- Rectal artesunate is an effective treatment for cerebral/complicated falciparum malaria in children.
- The rectal route facilitates rapid absorption and therapeutic drug concentrations.
- Further research is needed to optimize rectal artesunate regimens for malaria treatment in endemic regions.
Abstract:
We report the effectiveness of two regimens of rectal artesunate formulation in treating 13 Thai children with cerebral/complicated falciparum malaria. The drug was given at an initial dose of 40 mg/kg bodyweight, in 3 or 4 divided doses in the first 24 hours, followed by 10 mg/kg bodyweight once daily for three consecutive days. Mefloquine, at a dose of 15 mg/kg bodyweight was given orally at 72 hours after the initial dose of artesunate, followed by 10 mg/kg bodyweight 6 hours later. Three cases with cerebral malaria gained consciousness within 20 hours of artesunate administration. The median time required for reduction of parasitemia by 90% of the initial value (P90) in 13 children was 11.2 hours. No recrudescence was observed in any of the patients during the 28-day follow-up period. Plasma concentrations of artesunate and dihydroartemisinin (active plasma metabolite of artesunate) measured in two patients who received the high initial dose regimen (20 mg/ kg bodyweight) suggested rapid absorption and adequate plasma concentrations of both compounds following the administration of artesunate via the rectal route. Further studies for the optimized regimen of rectal artesunate in the treatment of cerebral/complicated childhood falciparum malaria in areas of multidrug resistance are warranted.
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