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

Background Systematic screening for active pulmonary tuberculosis (TB) is recommended for high-risk populations however the lack of an accurate, simple, and low-cost screening test that can be used in high burden areas is a major obstacle to its implementation. We evaluated whether C-reactive protein (CRP) possesses the necessary test characteristics to screen individuals for active pulmonary TB. Methods We performed a systematic review and meta-analysis of studies evaluating the diagnostic accuracy of CRP (cut-point of 10 mg/L) for pulmonary TB. We searched four databases for eligible articles published before January 31, 2015 and extracted data for individual studies. We synthesized data separately for outpatient and inpatient studies and generated pooled summary estimates (95% CI) for sensitivity and specificity using random-effects meta-analysis. We performed pre-specified subgroup analyses to determine pooled summary estimates of CRP for diagnosis-seeking vs. screening populations and for patients with and without HIV infection. Findings We identified nine unique studies enrolling 1723 patients from the outpatient and inpatient setting. In the outpatient setting, CRP had high sensitivity (93%, 95% CI: 85–97) and moderate specificity (62%, 95% CI: 42–79) for active pulmonary TB. CRP was just as sensitive and specific for active pulmonary TB among patients with confirmed HIV-infection. Among hospitalized patients, specificity of CRP was poor (21%, 95% CI: 6–52). Interpretation CRP shows considerable promise as a tool to facilitate systematic screening for active TB, even among PLHIV. CRP-based TB screening should now be studied in other high-risk groups to determine the full impact of this simple and low-cost test.

RationaleThe clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown.ObjectiveTo determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects.MethodsWe prospectively enrolled consecutive, hospitalized, Ugandan TB suspects in two phases: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase.Results477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73–84%) and specificity (190/199, 96%, 95% CI: 92–98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31–54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0–26] vs. 0 [IQR 0–1], p<0.001), and for smear-negative TB (35 [IQR 22–55] vs. 22 [IQR 0–33], p = 0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0–5] vs. 0 [IQR 0–2], p = 0.06) and for smear-negative TB (7 [IQR 3–53] vs. 6 [IQR 1–61], p = 0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: −21% to +27%, p = 0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: −34 to +46%, p = 0.77).ConclusionsXpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases.