Abstract
BackgroundThe haemolysis associated with clinical episodes of malaria results in the liberation of haem, which activates the enzyme haem oxygenase-1 (HO-1). HO-1 has been shown to reduce neutrophil function and increase susceptibility to invasive bacterial disease. However, the majority of community-associated malaria infections are subclinical, often termed “asymptomatic” and the consequences of low-grade haemolysis during subclinical malaria infection are unknown.Study design and resultsAs part of an ongoing study of subclinical malaria in Burkina Faso, 23 children with subclinical Plasmodium falciparum infections (determined by qPCR) were compared with 21 village-matched uninfected control children. Infected children showed evidence of persistent haemolysis over 35 days, with raised plasma haem and HO-1 concentrations. Concentrations of IL-10, which can also directly activate HO-1, were also higher in infected children compared to uninfected children. Regression analysis revealed that HO-1 was associated with haemolysis, but not with parasite density, anaemia or IL-10 concentration.ConclusionsThis study reveals that subclinical P. falciparum malaria infection is associated with sustained haemolysis and the induction of HO-1. Given the association between HO-1, neutrophil dysfunction and increased risk of Salmonella bacteraemia, prolonged HO-1 induction may explain epidemiological associations and geographic overlap between malaria and invasive bacterial disease. Further studies are needed to understand the consequences of persistent subclinical malaria infection, low-grade haemolysis and raised HO-1 on immune cell function and risk of comorbidities.
Highlights
The haemolysis associated with clinical episodes of malaria results in the liberation of haem, which activates the enzyme haem oxygenase-1 (HO-1)
This study reveals that subclinical P. falciparum malaria infection is associated with sustained haemolysis and the induction of HO-1
Further studies are needed to understand the consequences of persistent subclinical malaria infection, low-grade haemolysis and raised HO-1 on immune cell function and risk of comorbidities
Summary
The haemolysis associated with clinical episodes of malaria results in the liberation of haem, which activates the enzyme haem oxygenase-1 (HO-1). The vast majority of malaria infections that are detected in community surveys are ‘asymptomatic’, that is they do not present with fever or other obvious clinical signs that prompt treatment-seeking behaviour Individuals carrying these infections are often referred to as being ‘clinically immune’. Mooney et al Malar J (2018) 17:253 immune individuals harbour frequent, persistent or recurrent infections throughout their lives [7,8,9,10,11] These subclinical infections have been associated with persistent low-grade haemolysis, and fluctuations in parasite density may result in intermittent, higher density parasitaemia and further haemolysis [12, 13]. Very low parasite densities can lead to diagnostic confusion given the numerous comorbidities that may occur in malaria endemic regions [17]
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