Inhaled Nitric Oxide Protects From Fine Motor Impairment in Severe Malaria

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Approximately one-quarter of survivors of severe malaria experience neurologic disability.
Approximately one-quarter of survivors of severe malaria experience neurologic disability.

According to research published in PLos One, treatment with inhaled nitric oxide (NO) reduced the risk of fine motor impairment in pediatric patients with malaria.

Severe malaria is a leading cause of neurocognitive impairment in Africa. Reduced NO bioavailability is believed to be the mechanism, and several studies in animals and preterm neonates demonstrated a neuroprotective role for inhaled NO.

A randomized, double-blind, placebo-controlled study of the effects of inhaled NO in children aged 1 to 10 years and diagnosed with severe malaria was conducted in Uganda between 2011 and 2013 ( Identifier: NCT01255215).

Sixty-one children received inhaled NO for a maximum of 72 hours (80 parts per million), while 59 received placebo (room air); all children also received intravenous artesunate. Neurocognitive outcomes assessed were overall cognition, attention, associative memory, and the global executive composite.

Overall, 35% of children were impaired in at least one domain. There were no differences between groups in unadjusted and unadjusted age-adjusted z scores for overall cognition (β: 0.26; 95% CI: -0.19 to 0.72; P =.260), attention (β: 0.18; 95% CI: ‑0.14 to 0.51; P =.267), or memory (β: 0.14; 95% CI: -0.02 to 0.30; P =.094). Those receiving inhaled NO did have a 64% reduced relative risk of fine motor impairment vs the placebo group (relative risk, 0.36; 95% CI: 0.14-0.96) according to log binomial regression.

This study was limited by a short follow-up period and use of only one cognitive assessment. Therefore, the investigators stressed a need for studies to validate these results, specifically with longer follow-up times and larger sample sizes. Further, studies on the extent and mechanisms of cognitive impairment in severe malaria are also needed. Despite this, the data reported show the first evidence suggesting a beneficial long-term impact of adjunctive therapy in severe malaria.


Bangirana P, Conroy AL, Opoka RO, et al. Inhaled nitric oxide and cognition in pediatric severe malaria: a randomized double-blind placebo controlled trial. PLoS One. 2018;13(1): e0191550. 

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