Inhaled nitric oxide as adjunctive therapy for severe malaria: a randomized controlled trial

Area of Science:

• Pediatric Infectious Diseases
• Critical Care Medicine
• Cardiovascular Research

Background:

• Severe malaria is a leading cause of child mortality globally.
• Reduced nitric oxide is linked to severe and fatal malaria cases.
• Investigating inhaled nitric oxide (iNO) as a potential adjunctive therapy for severe malaria.

Purpose of the Study:

• To evaluate the efficacy of inhaled nitric oxide (iNO) as an adjunctive treatment for severe malaria in African children.
• To assess the impact of iNO on angiopoietin-2 (Ang-2) levels, a biomarker for malaria severity.

Main Methods:

• A randomized, double-blind, placebo-controlled trial involving 180 children with severe malaria.
• Participants received either iNO (80 ppm) or room air placebo alongside standard artesunate treatment.
• Primary outcome measured was the longitudinal course of angiopoietin-2 (Ang-2) levels over 72 hours.

Main Results:

• No significant difference in Ang-2 levels between the iNO and placebo groups.
• Similar mortality rates at 48 hours (6.9% vs 8.7%) and comparable clinical recovery and parasite clearance times.
• Methaemoglobinaemia occurred in 25% of iNO recipients but resolved without sequelae; other adverse events were similar between groups.

Conclusions:

• Inhaled nitric oxide (iNO) at 80 ppm was safe but did not alter Ang-2 levels or improve clinical outcomes in children with severe malaria.
• Alternative strategies to enhance endothelial nitric oxide bioavailability may be required for therapeutic benefit.
• Further research is needed to explore different methods for improving nitric oxide delivery or action in severe malaria.