Diagnostic accuracy of C-reactive protein and procalcitonin, compared with composite reference standards, to discriminate between tuberculosis, Pneumocystis jirovecii pneumonia and bacterial pneumonia in HIV-infected inpatients meeting WHO criteria for seriously ill

Abstract

Tuberculosis, bacterial community-acquired pneumonia (CAP), and Pneumocystis jirovecii pneumonia (PJP) are the commonest causes of hospitalisation in HIV-infected individuals. Prompt diagnosis and treatment initiation are important to reduce morbidity and mortality, but are hampered by overlap in clinical and radiological presentation and limited diagnostic resources in resource-poor settings. Simple, affordable tests are needed for developing improved clinical algorithms. C-reactive protein (CRP) and procalcitonin have shown diagnostic utility for respiratory tract infections, however few studies have focussed on their ability to distinguish between tuberculosis, CAP, and PJP in HIV-infected inpatients. We performed a cross-sectional study on secondary data to evaluate the diagnostic accuracy of Creactive protein (CRP) and procalcitonin compared to composite reference standards, for discrimination between the three target infections in adult HIV-infected inpatients. Participants had been recruited in two district level hospitals in Cape Town, South Africa, admitted with current cough and danger signs in accordance with the WHO algorithm for tuberculosis in seriously ill HIV-infected patients. Study clinicians were blinded to CRP and procalcitonin results and laboratory staff who performed biomarker tests on stored serum were blinded to patient diagnoses. 248 participants met study criteria and case definitions: 133 with tuberculosis, 61 with CAP, 16 with PJP, and 38 with mixed infection. Elevated CRP was found in 98% of participants. The cutoff used to guide antibiotic initiation in lower respiratory tract infections correctly identified 82% of those with CAP, 84% with tuberculosis and 50% with PJP. The differences in median CRP and procalcitonin concentrations between the three infections were statistically significant, but distributions overlapped considerably, and CRP and procalcitonin cut-offs with sensitivities of ≥ 90% were found for all three target infection pairs, however corresponding specificities were low. Receiver operating characteristic areas under the curve for CRP and procalcitonin were between 0.68 and 0.74 for PJP versus tuberculosis and PJP versus CAP. CRP and procalcitonin showed limited value in discriminating between the three target infections due to widely overlapping distributions, but diagnostic accuracy was higher for discriminating PJP from CAP or tuberculosis. Our findings suggest that CRP and procalcitonin may have greater diagnostic utility as part of a panel of biomarkers or in clinical prediction rules.