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Meta-Analysis
. 2019 May;78(5):339-348.
doi: 10.1016/j.jinf.2019.02.006. Epub 2019 Feb 22.

The utility of peripheral blood leucocyte ratios as biomarkers in infectious diseases: A systematic review and meta-analysis

Clark D Russell  1 , Arun Parajuli  2 , Hugo J Gale  3 , Naomi S Bulteel  4 , Philipp Schuetz  5 , Cornelis P C de Jager  6 , Anne J M Loonen  7 , Georgios I Merekoulias  8 , J Kenneth Baillie  9
Affiliations
Meta-Analysis

The utility of peripheral blood leucocyte ratios as biomarkers in infectious diseases: A systematic review and meta-analysis

Clark D Russell et al. J Infect. 2019 May.

Abstract

Objectives: To assess the utility of the neutrophil:lymphocyte (NLR), lymphocyte:monocyte (LMR) and platelet:lymphocyte ratios (PLR) as infection biomarkers.

Methods: PubMed/MEDLINE, Embase and Cochrane databases were searched to identify eligible articles. Studies of diagnosis, severity or outcome were included. PROSPERO systematic review registration CRD42017075032.

Results: Forty studies were included, reporting on bacterial and viral infections, malaria, and critical illness due to sepsis. Ten studies reported an association of higher NLR with bacteraemia, supported by meta-analysis of patient-level data (five studies, n = 3320; AUC 0.72, p<0.0001) identifying a cut-off of >12.65. Two studies reported an association with lower LMR and diagnosis of influenza virus infection in patients with respiratory tract infection. Meta-analysis of patient-level data (n = 85; AUC 0.66, p = 0.01) identified a cut-off of ≤2.06. The directionality of associations between NLR and outcomes in heterogeneous cohorts of critically ill adults with sepsis varied. Potential clinical utility was also demonstrated in pneumonia (NLR), pertussis (NLR), urinary tract infection (NLR), diabetic foot infections (NLR) and Crimean Congo Haemorrhagic Fever (PLR). Longitudinal measurement of LMR during respiratory virus infection reflected symptoms and NLR during sepsis and bacteraemia predicted mortality.

Conclusions: Peripheral blood leucocyte ratios are useful infection biomarkers, with the most evidence related to diagnosis of bacteraemia and influenza virus infection. In critical illness due to sepsis, a signal towards an association with NLR and outcomes exists, and NLR should be evaluated in future stratification models. Longitudinal measurement of ratios during infection could be informative. Overall, these biomarkers warrant further recognition and study in infectious diseases.

Keywords: Bacteremia; Blood platelets; Endotypes; Influenza; Lymphocytes; Monocytes; Neutrophils; Pneumonia; Sepsis; Stratified medicine.

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Figures

Fig.ure 1.
Fig. 1
PRISMA flow diagram illustrating article selection process.
Fig.ure 2.
Fig. 2
Infectious diseases and leucocyte ratios reported. a Infectious diseases and b leucocyte ratios reported in 40 included studies. Note that some studies reported more than one ratio and bacteraemia was reported separately in some studies so is included as an additional category when relevant, therefore each total exceeds 40. The ratios investigated in patients with infectious diseases shown in bold were considered to demonstrate potential clinical utility. CCHF: Crimean Congo haemorrhagic fever.
Fig.ure 3.
Fig. 3
Meta-analysis results for NLR and bacteraemia. a NLR median and interquartile range derived from meta-analysis of patient-level data for 3320 patients. b Receiver operator characteristic analysis for NLR in predicting presence of bacteraemia in these patients.
Fig.ure 4.
Fig. 4
Meta-analysis results for LMR and influenza virus infection. a LMR median and interquartile range derived from meta-analysis of patient-level data for 85 patients. b Receiver operator characteristic analysis for LMR in predicting presence of influenza virus infection in patients with symptomatic respiratory tract infection.
See this image and copyright information in PMC

Comment in

References

    1. Russell C.D., Baillie J.K. Treatable traits and therapeutic targets: goals for systems biology in infectious disease. Curr Opin Syst Biol. 2017;2:140–146. - PMC - PubMed
    1. Schuetz P., Wirz Y., Sager R., et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018;18(1):95–107. - PubMed
    1. Schuetz P., Wirz Y., Sager R., et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017;10 - PMC - PubMed
    1. de Jong E., van Oers J.A., Beishuizen A., et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819–827. - PubMed
    1. Hotchkiss R.S., Tinsley K.W., Swanson P.E., et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol. 2001;166(11):6952–6963. - PubMed

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