C-Reactive Protein as a Triage Test in Guiding Who Should Get a Confirmatory Test for Pulmonary Tuberculosis Diagnosis among Adults: A Case-Control Proof-of-Concept Study from Urban Tanzania

Abstract

Background: The current screening tools for tuberculosis (TB) are inadequate resulting in insufficient TB case detection and continued community transmission of TB. As the world is geared into finding missing TB cases, new strategies are called for to aid in rapid identification of TB cases. This study aimed to evaluate the role C-reactive protein (CRP) in triaging patients to get a definitive test for active pulmonary TB diagnosis in urban Tanzania. Methods: A case-control study was conducted among pulmonary TB (PTB) patients and contacts without active PTB. The diagnosis of PTB was performed using GeneXpert MTB/RIF assay and culture. Blood was collected from cases and controls for measuring CRP levels during recruitment. We compared socio-demographic characteristics, clinical and laboratory parameters obtained during recruitment and performed diagnostic accuracy analyses for CRP. Results: Out of all 193 study participants who were involved in final analysis, 147 (76.2%) were males. Pulmonary TB cases had significantly lower median BMI than controls (median 17.4 kg/m2 [IQR: 15.8 - 19.2 kg/m2] vs., 24.9 kg/m2 [IQR: 22.1 - 28.5 kg/m2), p < 0.001). There was no statistical difference in prevalence of HIV between PTB cases and controls i.e., 13.33% vs., 11.7%, p = 0.48. CRP was significantly higher in PTB cases vs., controls (median 67.8 mg/L, [IQR: 36.5 - 116.9 mg/L] vs., 1.55 mg/L, [IQR: 0.59 - 6.0 mg/L], p = 0.003). Furthermore, CRP at cut-off ≥10 mg/L was associated with best combination of sensitivity, specificity and area under the curve of 89.9%, 95% CI: 82.2 - 95.0, 80.9%, CI: 71.4 - 88.2 and 0.85, 95% CI: 0.80 - 0.90 respectively. A multivariate logistic regression model adjusted for fever, night sweats and body mass index showed that CRP above 10 mg/L was significantly associated with PTB, aOR 5.2, 95% CI 1.2 - 22.8. Conclusions: CRP at cut-off ≥10 mg/L can be used to screen pulmonary TB. These findings can be used to improve TB screening algorithm by incorporating CRP in combination with TB symptoms to identify patients who need further confirmatory TB tests. However, additional prospective studies are required to support our findings and contribute into policy recommendations on use of CRP in a screening algorithm for pulmonary TB.