• Brigitta Derendinger, Tessa K Mochizuki, Danaida Marcelo, Deepa Shankar, Wilson Mangeni, Hanh Nguyen, Seda Yerlikaya, William Worodria, Charles Yu, Nhung Viet Nguyen, Devasahayam Jesudas Christopher, Grant Theron, Patrick Pj Phillips, Payam Nahid, Claudia M Denkinger, Adithya Cattamanchi, and Christina Yoon.
• Stellenbosch University, DST-NRF Centre of Excellence for Biomedical Tuberculosis Research/SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Cape Town, South Africa.
• Am. J. Respir. Crit. Care Med. 2024 Dec 6.

AbstractRationale: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown. Objectives: In a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ≥90%, specificity ≥70%) for an effective TB screening test. Methods/Measurements: Consecutive outpatient adults with cough ≥2 weeks from five TB endemic countries in Africa and Asia had baseline blood collected for point-of-care CRP testing and HIV and diabetes screening. Sputum samples were collected for Xpert MTB/RIF Ultra (Xpert) testing and culture. CRP sensitivity and specificity (5 mg/L cut-point) was determined in reference to sputum test results and compared by country, sex, and HIV and diabetes status. Variables affecting CRP performance were identified using a multivariate receiver operating characteristic (ROC) regression model. Results: Among 2904 participants, of whom 613 (21%) had microbiologically-confirmed TB, CRP sensitivity was 84% (95% CI: 81-87%) and specificity was 61% (95% CI: 59-63%). CRP accuracy varied geographically, with higher sensitivity in African countries (≥91%) than Asian countries (64-82%). Sensitivity was higher among men than women (87% vs. 79%, difference +8%, 95% CI: 1-15%) and specificity was higher among people without HIV than PWH (64% vs. 45%, difference +19%, 95% CI: 13-25%). ROC regression identified country and measures of TB disease severity as predictors of CRP performance. Conclusions: Overall, CRP did not achieve the minimum accuracy targets and its performance varied by setting and in some sub-groups, likely reflecting population differences in mycobacterial load.

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