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

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.

Figure 1.

Study flowchart.

Figure 2.

Risk of bias and applicability concerns summary. This figure appears in color at www.ajtmh.org.

Figure 3.

Forest plot for studies on the accuracy of C-reactive protein. This figure appears in color at www.ajtmh.org.

Figure 4.

Summary receiver operating characteristic displaying the accuracy of C-reactive protein. This figure appears in color at www.ajtmh.org.

Figure 5.

Forest plot for studies on the accuracy of procalcitonin. This figure appears in color at www.ajtmh.org.