The University of Southampton
University of Southampton Institutional Repository

Inhaled nitric oxide as an adjunctive treatment for cerebral malaria in children: a phase II randomized open-label clinical trial

Inhaled nitric oxide as an adjunctive treatment for cerebral malaria in children: a phase II randomized open-label clinical trial
Inhaled nitric oxide as an adjunctive treatment for cerebral malaria in children: a phase II randomized open-label clinical trial
Background: Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods: This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate. We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results: Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-?, interferon-?, interleukin [IL]-1?, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels—blood methemoglobin and plasma nitrate—increased in patients treated with NO (both P < .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions: Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours.
cerebral malaria, methemoglobin, nitric oxide, plasmodium falciparum
1-9
Mwanga-Amumpaire, Juliet
6cda067d-5796-4a59-aca9-ea3c26422eb6
Carroll, Ryan W.
6a376361-8150-4121-a816-bce2e8df83a9
Baudin, Elisabeth
f54a35e0-1a5b-4ebd-8bc4-8ec2b7cdf811
Kemigisha, Elisabeth
be5f9130-3e7d-4f89-8394-32c15795b8cf
Nampijja, Dorah
6bf8e89b-4468-4336-aadf-f32eb790e360
Mworozi, Kenneth
3cf042c9-70f1-4892-84d8-e3f5e592c7c0
Santorino, Data
20fc5e23-07f7-4a57-8d7c-71ac04a344d2
Nyehangane, Dan
eb74a151-a319-435e-81de-50e92c889492
Nathan, Daniel I.
931af947-d554-4b35-b555-2ba82648cb0b
De Beaudrap, Pierre
edc96c1b-f034-4c49-be32-3b9c1d9fd59b
Etard, Jean-François
ac035d6e-795f-401a-8d61-c380b7d9ac07
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Berssenbrugge, Annie
edff649f-8143-40a6-8e2d-9f0e1c068484
Bangsberg, David
87f20674-8515-4036-9b40-24eeaedcb530
Bloch, Kenneth D.
25d43ddf-77d4-448b-b618-079a0492aba1
Boum, Yap
59579b35-abae-4b0d-9e68-eb87637d7ef3
Zapol, Warren M.
84efe66d-166f-4b1d-8db2-b48586aea27e
Mwanga-Amumpaire, Juliet
6cda067d-5796-4a59-aca9-ea3c26422eb6
Carroll, Ryan W.
6a376361-8150-4121-a816-bce2e8df83a9
Baudin, Elisabeth
f54a35e0-1a5b-4ebd-8bc4-8ec2b7cdf811
Kemigisha, Elisabeth
be5f9130-3e7d-4f89-8394-32c15795b8cf
Nampijja, Dorah
6bf8e89b-4468-4336-aadf-f32eb790e360
Mworozi, Kenneth
3cf042c9-70f1-4892-84d8-e3f5e592c7c0
Santorino, Data
20fc5e23-07f7-4a57-8d7c-71ac04a344d2
Nyehangane, Dan
eb74a151-a319-435e-81de-50e92c889492
Nathan, Daniel I.
931af947-d554-4b35-b555-2ba82648cb0b
De Beaudrap, Pierre
edc96c1b-f034-4c49-be32-3b9c1d9fd59b
Etard, Jean-François
ac035d6e-795f-401a-8d61-c380b7d9ac07
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Berssenbrugge, Annie
edff649f-8143-40a6-8e2d-9f0e1c068484
Bangsberg, David
87f20674-8515-4036-9b40-24eeaedcb530
Bloch, Kenneth D.
25d43ddf-77d4-448b-b618-079a0492aba1
Boum, Yap
59579b35-abae-4b0d-9e68-eb87637d7ef3
Zapol, Warren M.
84efe66d-166f-4b1d-8db2-b48586aea27e

Mwanga-Amumpaire, Juliet, Carroll, Ryan W. and Baudin, Elisabeth et al. (2015) Inhaled nitric oxide as an adjunctive treatment for cerebral malaria in children: a phase II randomized open-label clinical trial. Open Forum Infectious Diseases, 2 (3), 1-9, [ofv111]. (doi:10.1093/ofid/ofv111). (PMID:26309894)

Record type: Article

Abstract

Background: Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods: This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate. We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results: Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-?, interferon-?, interleukin [IL]-1?, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels—blood methemoglobin and plasma nitrate—increased in patients treated with NO (both P < .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions: Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours.

Text
2015 Mwanga-Amupaire Open J Inf Dis.pdf - Other
Download (520kB)

More information

Accepted/In Press date: 21 July 2015
Published date: 24 July 2015
Additional Information: Funding Information: Financial support. This work was supported by financial contributions from the International Innovation Fund of Médecins Sans Frontières (MSF) and MSF France; the Anesthesia Center for Critical Care Research and the Department of Anesthesia, Critical Care, and Pain Medicine of Massachusetts General Hospital (Boston, MA); and the Mark and Lisa Schwartz Foundation. This study would not have been possible without generous gas and equipment support from Ikaria and Masimo, and funding for the NO metabolite assays from the University of Southampton School of Medicine, UK. Funding Information: This work was supported by financial contributions from the International Innovation Fund of Médecins Sans Frontières (MSF) and MSF France; the Anesthesia Center for Critical Care Research and the Department of Anesthesia, Critical Care, and Pain Medicine of Massachusetts General Hospital (Boston, MA); and the Mark and Lisa Schwartz Foundation. This study would not have been possible without generous gas and equipment support from Ikaria and Masimo, and funding for the NO metabolite assays from the University of Southampton School of Medicine, UK. Publisher Copyright: © 2022 The Author.
Keywords: cerebral malaria, methemoglobin, nitric oxide, plasmodium falciparum
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 381156
URI: http://eprints.soton.ac.uk/id/eprint/381156
PURE UUID: 4eb5d0be-cd4f-4594-8b9b-c7776fe15e50
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158
ORCID for Bernadette O. Fernandez: ORCID iD orcid.org/0000-0001-6337-0381

Catalogue record

Date deposited: 05 Oct 2015 11:46
Last modified: 18 Mar 2024 03:24

Export record

Altmetrics

Contributors

Author: Juliet Mwanga-Amumpaire
Author: Ryan W. Carroll
Author: Elisabeth Baudin
Author: Elisabeth Kemigisha
Author: Dorah Nampijja
Author: Kenneth Mworozi
Author: Data Santorino
Author: Dan Nyehangane
Author: Daniel I. Nathan
Author: Pierre De Beaudrap
Author: Jean-François Etard
Author: Martin Feelisch ORCID iD
Author: Bernadette O. Fernandez ORCID iD
Author: Annie Berssenbrugge
Author: David Bangsberg
Author: Kenneth D. Bloch
Author: Yap Boum
Author: Warren M. Zapol

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×