Molecular signatures of severe acute infections in Hospitalised children
Sepsis is a heterogeneous syndrome characterised by organ dysfunction caused by arndysregulated host response to infection. It is accountable for substantial morbidity and mortality inrnchildren globally. Different pathogens such as bacteria viruses parasites or fungi cause infectionsrnthat manifest with sepsis-like symptoms thus limiting symptomatic clinical diagnosis. In additionrnoutcomes of hospitalised sepsis patients are difficult to predict. Characterizing the aetiology and riskrnstratifying sepsis patients remain a challenge globally but mostly in low- and middle-income countriesrndue to limited diagnostic and prognostic capacity. This complicates care decisions leading to increasedrnantimicrobial resistance and mortality. Preventing death and long-term morbidity due to infectiousrndiseases requires better diagnostics and new therapeutics to treat serious complications of infectionsrnsuch as sepsis. Understanding the molecular processes that underlie different sepsis aetiologies andrnoutcomes would enable initiation of appropriate and timely treatment. We aimed to characterise the hostrnresponse in plasma of children under 5 years admitted at the Kilifi County Hospital with severe acuterninfections.
We aimed to characterise the hostrnresponse in plasma of children under 5 years admitted at the Kilifi County Hospital with severe acuterninfections.
Admission levels of plasma proteins were determined using untargeted liquidrnchromatography tandem mass spectrometry LC-MS/MS. Protein profiles of children with bacterialrninfections N 63 were compared with those of children who had viral infections N75. Healthyrnchildren N20 were used as controls. Protein profiles of children who had bacterial infections wererncompared to those who had viral infections. Using linear models we assessed the relationship betweenrnbaseline plasma proteins and infection
Bioinformatic analysis of differentially expressed proteins showed elevation of alreadyrncharacterised acute phase proteins such as C-reactive protein in children with bacterial infections.rnIn addition angiotensinogen lipopolysaccharide binding protein Serpin Family A Member 1rnSerpin Family A Member 3 were associated with bacterial infections while Apolipoprotein A-2 andrnparaoxonase-1 were associated with viral infections. Acute phase responses toll-like receptor signallingrnand neutrophil degranulation were enriched in bacterial infections while platelet degranulation wasrnnegatively associated with bacterial infections.
These results show the changes plasma protein levels and biological processes duringrnbacterial and viral sepsis that can be leveraged to design future interventions of sepsis.
Publication Information
Focus County(s):
Kilifi County
Programme Area(s):
Research Priority Area(s):
Disease Domain(s):
Document History:
Publication Date: 01.Jan.1970
Conference Title: