Lactic acidosis and oxygen debt in African children with severe anaemia

Severe anaemia and invasive bacterial infections are common causes of childhood sickness and death in sub-Saharan Africa. Accumulating evidence suggests that severely anaemic African children may have a higher risk of invasive bacterial infections. However, the mechanisms underlying this association remain poorly described. Severe anaemia is characterized by increased haemolysis, erythropoietic drive, gut permeability, and disruption of immune regulatory systems. These pathways are associated with dysregulation of iron homeostasis, including the downregulation of the hepatic hormone hepcidin. Increased haemolysis and low hepcidin levels potentially increase plasma, tissue and intracellular iron levels. Pathogenic bacteria require iron and/or haem to proliferate and have evolved numerous strategies to acquire labile and protein-bound iron/haem. In this review, we discuss how severe anaemia may mediate the risk of invasive bacterial infections through dysregulation of hepcidin and/or iron homeostasis, and potential studies that could be conducted to test this hypothesis.

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Identifying Prognostic Factors of Severe Metabolic Acidosis and Acute Kidney Injury in African Children with Severe Falciparum Malaria: A Secondary Analysis of A Randomised Trial

10.21203/rs.3.rs-148298/v1 ◽

2021 ◽

Author(s):

Grace Wezi Mzumara ◽

Stije Stije Leopold ◽

Kevin Marsh ◽

Arjen Dondorp ◽

Eric Ohuma ◽

...

Keyword(s):

Acute Kidney Injury ◽

Prognostic Factors ◽

Metabolic Acidosis ◽

Falciparum Malaria ◽

Kidney Injury ◽

Severe Anaemia ◽

Severe Metabolic Acidosis ◽

Prognostic Features ◽

African Children ◽

Severe Falciparum Malaria

Abstract IntroductionSevere metabolic acidosis and acute kidney injury are major causes of mortality in children with severe malaria but are often underdiagnosed in low resource settings. MethodsWe conducted a retrospective analysis of the ‘Artesunate vs Quinine in the treatment of severe falciparum malaria in African children’ (AQUAMAT) trial to identify clinical features of severe metabolic acidosis and acute kidney injury in 5425 children from nine African countries. Separate models were fitted for acute kidney injury and severe metabolic acidosis. Separate univariable and multivariable logistic regression were performed to identify prognostic factors for severe metabolic acidosis (SMA) and acute kidney injury (AKI). 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. ResultsThere were 2296 children identified with Severe metabolic acidosis and 1110 with Acute Kidney Injury. Prognostic features of SMA among them were: deep breathing (OR: 5.41, CI: 4.26 – 6.89), hypoglycaemia (OR: 5.22, CI: 3.80 – 7.18), AKI (OR: 3.99, CI: 3.30 – 4.81), coma ( OR: 1.79 CI: 1.36 – 2.35), respiratory distress (OR: 1.49, CI: 1.21 – 1.83), prostration (OR: 1.64 CI: 1.30 – 2.03) and severe anaemia (OR: 1.40, CI: 1.11 – 1.77). Features associated with AKI were; older children(OR: 1.20, CI: 1.15 – 1.25), coma (2.47, CI: 1.78 – 3.42), Prostration (OR: 1.52 CI: 1.14 – 2.02), decompensated shock (OR: 1.74, CI: 1.15 – 2.63), black water fever (CI: 1.81. CI: 1.22 – 2.69), jaundice (OR: 3.31 CI: 2.01 – 5.47), SMA (OR: 4.02 CI:3.30 – 4.89), mild anaemia (OR: 1.36, CI: 1.05 – 1.76), severe anaemia (OR: 1.48, CI: 1.11 – 1.96), hypoglycaemia (OR: 2.02, CI: 1.58 – 2.59), hypernatremia (OR: 5.74, CI: 2.69 – 12.26) and hyperkalaemia (OR: 5.31. CI: 4.15 – 6.80). ConclusionClinical and laboratory parameters representing contributors and consequences of severe metabolic acidosis and acute kidney injury 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.

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