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Usefulness of C-Reactive Protein and Other Host BioMarker Point-of-Care Tests in the Assessment of Non-Malarial Acute Febrile Illnesses: A Systematic Review with Meta-Analysis

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  • 1 Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Verona, Italy;
  • 2 Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy;
  • 3 Scuola di Medicina, Università degli studi di Verona, Verona, Italy;
  • 4 Scuola di Specializzazione in Malattie Infettive, Università degli Studi di Verona, Verona, Italy;
  • 5 Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom;
  • 6 Foundation for Innovative Diagnostics (FIND), Geneva, Switzerland;
  • 7 Diagnostic and Public Health Department, Infectious Diseases and Tropical Medicine Section, University of Verona, Verona, Italy

ABSTRACT

In low- and middle-income countries, in resource-limited settings, the implementation of diagnostic tools discriminating bacterial from nonbacterial fever is a matter of primary concern. The introduction of malaria rapid diagnostic tests highlighted the need for point-of-care tests (POCTs) supporting clinical decision-making for non-malarial febrile illnesses. The purpose of this work was to review the use of host biomarker POCTs for the assessment of acute non-malarial fever in resource-constraint settings. Specific objectives were as follows: 1) to estimate the accuracy of such tests in differentiating fever of bacterial from nonbacterial origin and 2) to assess the impact of host biomarkers on antibiotic prescription and clinical outcome. We conducted a systematic review searching PubMed, Embase, the Cochrane Library, and Bireme. The protocol was registered with PROSPERO (n CRD42019141735). Data on the accuracy of C-reactive protein (CRP) for the detection of bacterial infections were meta-analyzed using the hierarchical summary receiver operating characteristic model, obtaining a summary ROC (SROC). We identified 2,192 articles, eight of which were included in the review. Among the different biomarkers evaluated, CRP was the one most frequently studied. The SROC presented an area under the curve = 0.77 (CI: 0.73–0.81), which indicates good accuracy to distinguish bacterial from nonbacterial infections. However, the optimal cutoff of CRP could not be assessed, and we found insufficient evidence about its impact on antibiotic prescription and clinical outcome. The role of CRP and other host biomarker POCTs for the assessment of acute non-malarial febrile illnesses in resource-constraint settings deserves further studies.

Author Notes

Address correspondence to Giulia Bertoli, Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via don A. Sempreboni 5, Negrar di Valpolicella, Verona 37024, Italy. E-mail: giulia.bertoli@sacrocuore.it

Disclosure: This work was supported by the Italian Ministry of Health “Fondi Ricerca Corrente-Linea 1, progetto 1” to IRCCS Sacro Cuore Don Calabria Hospital.

Authors’ addresses: Giulia Bertoli, Niccolò Ronzoni, Ronaldo Silva, Tamara Ursini, and Dora Buonfrate, Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Verona, Italy, E-mails: giulia.bertoli@sacrocuore.it, niccolo.ronzoni@sacrocuore.it, ronaldo.silva@sacrocuore.it, tamara.ursini@sacrocuore.it, and dora.buonfrate@sacrocuore.it. Michele Spinicci and Alessandro Bartoloni, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy, E-mails: michele.spinicci@unifi.it and alessandro.bartoloni@unifi.it. Chiara Perlini, Scuola di Medicina, Università degli studi di Verona, Verona, Italy, E-mail: chiaretta.perlini@gamil.com. Luca Omega, Scuola di Specializzazione in Malattie Infettive, Università degli Studi di Verona, Verona, Italy, E-mail: luca.omega1@gmail.com. Piero Olliaro, Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom, and Foundation for Innovative Diagnostics (FIND), Geneva, Switzerland, E-mail: piero.olliaro@ndm.ox.ac.uk. Zeno Bisoffi, Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Verona, Italy, and Infectious Diseases and Diagnostic and Public Health Department, Tropical Medicine Section, University of Verona, Verona, Italy, E-mail: zeno.bisoffi@sacrocuore.it.

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