Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study

Abstract

Background Symptom-based screening for tuberculosis (TB) is recommended for all people living with HIV (PLHIV) resulting in unnecessary Xpert MTB/RIF testing for the vast majority of individuals living in TB endemic areas and thus, poor implementation of intensified case finding (ICF) and TB preventive therapy. Novel approaches to TB screening are therefore critical in achieving global targets for TB elimination. Methods In a prospective study of PLHIV with CD4+ T-cell count ≤350 cells/uL initiating antiretroviral therapy (ART) from two HIV/AIDS clinics in Uganda, we evaluated the performance of C-reactive protein (CRP) measured using a rapid and inexpensive point-of-care (POC) assay as a screening tool for active pulmonary TB. Findings Of 1177 HIV-infected adults (median CD4+ T-cell count 168 cells/µL) enrolled, 163 (14%) had culture-confirmed TB. POC CRP had 89% (145/163) sensitivity and 72% (731/1014) specificity for culture-confirmed TB. Compared to the WHO symptom screen, POC CRP had lower sensitivity (difference −7% [95% CI: −12 to −2], p=0.002) but substantially higher specificity (difference +58% [95% CI: +61 to +55], p<0.0001). When Xpert MTB/RIF results were used as the reference standard, sensitivity of POC CRP and the WHO symptom screen were similar (94% [79/84] vs. 99% [83/84]; difference −5% [95% CI: −12 to +2], p=0.10). Interpretation The performance characteristics of CRP support its use as a TB screening test for PLHIV with CD4+ T-cell count ≤350 cells/µL initiating ART. HIV/AIDS programs should consider POC CRP-based TB screening to improve the efficiency of ICF and increase uptake of TB preventive therapy. FUNDING National Institutes of Health; Presidential Emergency Plan for AIDS Relief; University of California, San Francisco, Nina Ireland Program for Lung Health

Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults

“…Eleven studies (4196 participants) reported a higher percentage (> 25%) of participants with a history of tuberculosis ( Adelman 2015 ; Al‐Darraji 2013 ; Boehme 2010 ; Kawkitinarong 2017 ; Ko 2016 ; Lawn 2011 ; Mutingwende 2015 ; O'Donnell 2015 ; Reddy 2017 ; Reechaipichitkul 2017 ; Theron 2011 ) and 16 studies (8205 participants) reported a lower percentage (≤ 25%) of participants with a history of tuberculosis ( Balcha 2014 ; Barmankulova 2015 ; Bates 2013a ; Bjerrum 2016 ; Boehme 2010 ; Boum 2016 ; Carriquiry 2012 ; Dorman 2018 ; Hanrahan 2013 ; Helb 2010 ; LaCourse 2016 ; Luetkemeyer 2016 ; Mbelele 2017 ; Scott 2017 ; Sohn 2014 ; Yoon 2017 ). In studies with a higher percentage of participants with previous tuberculosis, Xpert MTB/RIF pooled sensitivity (95% CrI) was 86% (82% to 89%), similar to the pooled sensitivity of 85% (81% to 89%) in studies with a lower percentage of participants with previous tuberculosis.…”

“… Adelman 2015 and Al‐Darraji 2013 included few tuberculosis cases. Yoon 2017 enrolled HIV‐positive people initiating antiretroviral therapy. Lawn 2011 included HIV‐positive participants irrespective of tuberculosis symptoms.…”

Can we predict tuberculosis cure? What tools are available?

“…Circulating levels of C-reactive protein (CRP), an established biomarker of systemic inflammation, has been described to reflect TB disease severity and radiographic improvement after 2 months of treatment [162,163]. In an African study, CRP decreased significantly after 2 months of treatment, whereas levels of β 2 -microglobulin, a component of class I MHC found in a free state in various body fluids in different disease pathologies [164], and neopterin, a clinical marker of immune activation during inflammation [165] showed little change by 2 months, but a significant decrease after 6 months of treatment [166].…”

Soluble CD14 as a Diagnostic Biomarker for Smear-Negative HIV-Associated Tuberculosis

“…Another simple method is the measurement of C-reactive protein (CRP), an acute-phase protein that rapidly increases following the induction of inflammation due to infectious, autoimmune, or other inflammatory diseases [ 17 , 18 , 19 , 20 , 21 ]. As such, increased CRP levels are non-specific, but elevated levels have been documented in TB with or without HIV co-infection ([ 22 , 23 , 24 , 25 , 26 , 27 ] and reviewed by Yoon et al 2017 [ 28 ]). Since CRP is already available as a rapid blood test in the clinical setting, it was found to be useful as a screening tool for HIV-associated TB in recent studies [ 22 , 24 , 26 , 27 ].…”