Identifying prognostic factors of severe metabolic acidosis and uraemia in African children with severe falciparum malaria: a secondary analysis of a randomized trial.


Journal

Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802

Informations de publication

Date de publication:
25 Jun 2021
Historique:
received: 13 01 2021
accepted: 27 05 2021
entrez: 26 6 2021
pubmed: 27 6 2021
medline: 12 10 2021
Statut: epublish

Résumé

Severe metabolic acidosis and acute kidney injury are major causes of mortality in children with severe malaria but are often underdiagnosed in low resource settings. A retrospective analysis of the 'Artesunate versus quinine in the treatment of severe falciparum malaria in African children' (AQUAMAT) trial was conducted to identify clinical features of severe metabolic acidosis and uraemia in 5425 children from nine African countries. Separate models were fitted for uraemia and severe metabolic acidosis. Separate univariable and multivariable logistic regression were performed to identify prognostic factors for severe metabolic acidosis and uraemia. Both analyses adjusted for the trial arm. A forward selection approach was used for model building of the logistic models and a threshold of 5% statistical significance was used for inclusion of variables into the final logistic model. Model performance was assessed through calibration, discrimination, and internal validation with bootstrapping. There were 2296 children identified with severe metabolic acidosis and 1110 with uraemia. Prognostic features of severe metabolic acidosis among them were deep breathing (OR: 3.94, CI 2.51-6.2), hypoglycaemia (OR: 5.16, CI 2.74-9.75), coma (OR: 1.72 CI 1.17-2.51), respiratory distress (OR: 1.46, CI 1.02-2.1) and prostration (OR: 1.88 CI 1.35-2.59). Features associated with uraemia were coma (3.18, CI 2.36-4.27), Prostration (OR: 1.78 CI 1.37-2.30), decompensated shock (OR: 1.89, CI 1.31-2.74), black water fever (CI 1.58. CI 1.09-2.27), jaundice (OR: 3.46 CI 2.21-5.43), severe anaemia (OR: 1.77, CI 1.36-2.29) and hypoglycaemia (OR: 2.77, CI 2.22-3.46) CONCLUSION: Clinical and laboratory parameters representing contributors and consequences of severe metabolic acidosis and uraemia were independently associated with these outcomes. The model can be useful for identifying patients at high risk of these complications where laboratory assessments are not routinely available.

Sections du résumé

BACKGROUND BACKGROUND
Severe metabolic acidosis and acute kidney injury are major causes of mortality in children with severe malaria but are often underdiagnosed in low resource settings.
METHODS METHODS
A retrospective analysis of the 'Artesunate versus quinine in the treatment of severe falciparum malaria in African children' (AQUAMAT) trial was conducted to identify clinical features of severe metabolic acidosis and uraemia in 5425 children from nine African countries. Separate models were fitted for uraemia and severe metabolic acidosis. Separate univariable and multivariable logistic regression were performed to identify prognostic factors for severe metabolic acidosis and uraemia. Both analyses adjusted for the trial arm. A forward selection approach was used for model building of the logistic models and a threshold of 5% statistical significance was used for inclusion of variables into the final logistic model. Model performance was assessed through calibration, discrimination, and internal validation with bootstrapping.
RESULTS RESULTS
There were 2296 children identified with severe metabolic acidosis and 1110 with uraemia. Prognostic features of severe metabolic acidosis among them were deep breathing (OR: 3.94, CI 2.51-6.2), hypoglycaemia (OR: 5.16, CI 2.74-9.75), coma (OR: 1.72 CI 1.17-2.51), respiratory distress (OR: 1.46, CI 1.02-2.1) and prostration (OR: 1.88 CI 1.35-2.59). Features associated with uraemia were coma (3.18, CI 2.36-4.27), Prostration (OR: 1.78 CI 1.37-2.30), decompensated shock (OR: 1.89, CI 1.31-2.74), black water fever (CI 1.58. CI 1.09-2.27), jaundice (OR: 3.46 CI 2.21-5.43), severe anaemia (OR: 1.77, CI 1.36-2.29) and hypoglycaemia (OR: 2.77, CI 2.22-3.46) CONCLUSION: Clinical and laboratory parameters representing contributors and consequences of severe metabolic acidosis and uraemia were independently associated with these outcomes. The model can be useful for identifying patients at high risk of these complications where laboratory assessments are not routinely available.

Identifiants

pubmed: 34172046
doi: 10.1186/s12936-021-03785-0
pii: 10.1186/s12936-021-03785-0
pmc: PMC8234663
doi:

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

282

Références

Malar J. 2013 Nov 15;12:423
pubmed: 24237749
Clin Infect Dis. 2005 Oct 1;41(7):948-57
pubmed: 16142658
Lancet. 2014 Feb 22;383(9918):723-35
pubmed: 23953767
Crit Care. 2015 Sep 07;19:317
pubmed: 26343146
BMC Med. 2019 May 21;17(1):98
pubmed: 31109328
PLoS One. 2012;7(9):e45645
pubmed: 23029157
Trans R Soc Trop Med Hyg. 1996 Nov-Dec;90(6):658-62
pubmed: 9015508
BMC Med. 2019 Jul 8;17(1):124
pubmed: 31280724
Open Forum Infect Dis. 2016 Feb 26;3(2):ofw046
pubmed: 27186577
Am J Trop Med Hyg. 1996 Nov;55(5):521-4
pubmed: 8940984
Trans R Soc Trop Med Hyg. 1993 Nov-Dec;87(6):662-5
pubmed: 8296367
Blood Purif. 2020;49(1-2):185-196
pubmed: 31851976
PLoS One. 2012;7(12):e51229
pubmed: 23251463
N Engl J Med. 2011 Jun 30;364(26):2483-95
pubmed: 21615299
Malar J. 2018 Mar 23;17(1):128
pubmed: 29566677
Virulence. 2020 Dec;11(1):199-221
pubmed: 32063099
Perit Dial Int. 2016 Mar-Apr;36(2):213-7
pubmed: 26429418
Trop Med Int Health. 1999 May;4(5):390-4
pubmed: 10402976
Lancet Glob Health. 2016 Apr;4(4):e242-50
pubmed: 27013312
Infection. 2020 Feb;48(1):143-146
pubmed: 31686322
Clin Infect Dis. 1992 Nov;15(5):874-80
pubmed: 1445988
Trans R Soc Trop Med Hyg. 1998 May-Jun;92(3):305-8
pubmed: 9861404
Lancet. 2010 Nov 13;376(9753):1647-57
pubmed: 21062666
Nephron Clin Pract. 2012;120(4):c179-84
pubmed: 22890468
Crit Care Med. 2004 Aug;32(8):1683-8
pubmed: 15286544
QJM. 1997 Apr;90(4):263-70
pubmed: 9307760
Int J Epidemiol. 2016 Dec 1;45(6):1887-1894
pubmed: 28089956
Acta Paediatr. 2012 Nov;101(11):e514-8
pubmed: 22931368
Clin Infect Dis. 2012 Apr;54(8):1080-90
pubmed: 22412067
Clin Infect Dis. 2011 Sep;53(6):548-54
pubmed: 21865191
Malar J. 2006 Oct 26;5:93
pubmed: 17067375
N Engl J Med. 1995 May 25;332(21):1399-404
pubmed: 7723795
Q J Med. 1993 Feb;86(2):99-109
pubmed: 8464997
Trends Parasitol. 2005 Jan;21(1):11-6
pubmed: 15639735
Arch Dis Child. 1995 Apr;72(4):334-6
pubmed: 7763067
Curr Opin Infect Dis. 2018 Feb;31(1):69-77
pubmed: 29206655
QJM. 2003 Jun;96(6):427-34
pubmed: 12788961
Clin Infect Dis. 2008 Jul 15;47(2):151-7
pubmed: 18533842
Malar J. 2018 Dec 18;17(1):477
pubmed: 30563520

Auteurs

Grace Mzumara (G)

Malawi Liverpool Wellcome Trust, Queen Elizabeth Central Hospital College of Medicine, Chichiri 3, P.O. Box 30096, Blantyre, Malawi. gmzumara@mlw.mw.
University of Malawi, College of Medicine, Blantyre, Malawi. gmzumara@mlw.mw.
University of Oxford, Oxford, UK. gmzumara@mlw.mw.
Centre for Tropical Medicine and Global Health, Oxford, UK. gmzumara@mlw.mw.

Stije Leopold (S)

Centre for Tropical Medicine and Global Health, Oxford, UK.
Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.

Kevin Marsh (K)

Centre for Tropical Medicine and Global Health, Oxford, UK.
KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.

Arjen Dondorp (A)

Centre for Tropical Medicine and Global Health, Oxford, UK.
Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.

Eric O Ohuma (EO)

University of Oxford, Oxford, UK.
Centre for Tropical Medicine and Global Health, Oxford, UK.
Maternal, Adolescent, Reproductive and Child Health (MARCH) Centre, School of Hygiene and Tropical Medicine (LSHTM), London, UK.

Mavuto Mukaka (M)

University of Malawi, College of Medicine, Blantyre, Malawi.
University of Oxford, Oxford, UK.
Centre for Tropical Medicine and Global Health, Oxford, UK.
Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.

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Classifications MeSH