Value of C-reactive protein in differentiating viral from bacterial aetiologies in patients with non-malaria acute undifferentiated fever in tropical areas: a meta-analysis and individual patient data study

Abstract

C-reactive protein (CRP) is used to discriminate common bacterial and viral infections, but its utility in tropical settings remains unknown. We performed a meta-analysis of studies performed in Asia and Africa. First, mean CRP levels for specific tropical infections were calculated. Thereafter, individual patient data (IPD) from patients with non-malarial undifferentiated fever (NMUF) who were tested for viral and bacterial pathogens were analysed, calculating separate cut-off values and their performance in classifying viral or bacterial disease. Mean CRP levels of 7307 patients from 13 countries were dengue 12.0 mg/l (standard error [SE] 2.7), chikungunya 41.0 mg/l (SE 19.5), influenza 15.9 mg/l (SE 6.3), Crimean–Congo haemorrhagic fever 9.7 mg/l (SE 4.7), Salmonella 61.9 mg/l (SE 5.4), Rickettsia 61.3 mg/l (SE 8.8), Coxiella burnetii 98.7 mg/l (SE 44.0) and Leptospira infections 113.8 mg/l (SE 23.1). IPD analysis of 1059 NMUF patients ≥5 y of age showed CRP <10 mg/l had 52% sensitivity (95% confidence interval [CI] 48 to 56) and 95% specificity (95% CI 93 to 97) to detect viral infections. CRP >40 mg/l had 74% sensitivity (95% CI 70 to 77) and 84% specificity (95% CI 81 to 87) to identify bacterial infections. Compared with routine care, the relative risk for incorrect classification was 0.64 (95% CI 0.55 to 0.75) and the number needed to test for one extra correctly classified case was 8 (95% CI 6 to 12). A two cut-off value CRP test may help clinicians to discriminate viral and bacterial aetiologies of NMUF in tropical areas.

C-Reactive Protein for the Early Assessment of Non-Malarial Febrile Patients: A Retrospective Diagnostic Study

“…Erring on the side of caution to minimise the risk of missing cases that require antibiotics means that a relatively low cut-off value (like the 11 mg/L found here) may not have a huge impact on antibiotic prescriptions. Our findings are in line with a recent meta-analysis and individual patient data study [13], which showed that a CRP cut-off close to the one found here (10 mg/L) achieved very high sensitivity for bacterial infections. However, the optimal accuracy was found at 36 mg/L, and at a threshold of 40 mg/L the sensitivity and specificity for bacterial infections were 74% (95% CI 70-77) and 84% (95% CI 81-87), respectively.…”

Model-based cost-effectiveness analysis of a multiplex lateral flow rapid diagnostic test for acute non-malarial febrile illness in rural South and Southeast Asian primary care

“…10 This latter assertion is also supported by data from a study showing that a CRP level >40 mg/ml had a sensitivity of 74% for detecting bacterial infections in acutely febrile patients. 11 While such a multiplex test has not yet been developed, assessment of its potential costeffectiveness is essential to assist in guiding the research and policymaking processes that will underpin its successful development and implementation in the target settings. In this study, we aimed, therefore, to assess the cost-effectiveness in two tropical lower-middle income countries, one in Southeast Asia (Cambodia) and one in South Asia (Bangladesh), of a novel putative multiplex LF-RDT which measures CRP in addition to being able to diagnose acute enteric fever (e.g., by detecting typhoidal Salmonella antigens) and dengue (e.g., by detecting dengue NS1 antigen and dengue IgM) in patients with acute NMFI, in line with the results of the abovementioned Delphi survey.…”

“…10 This latter assertion is also supported by data from a study showing that a CRP level >40 mg/ml had a sensitivity of 74% for detecting bacterial infections in acutely febrile patients. 11…”