Yield and Efficiency of Novel Intensified Tuberculosis Case-Finding Algorithms for People Living with HIV

Abstract

Rationale: The recommended tuberculosis (TB) intensified case finding (ICF) algorithm for people living with HIV (symptom-based screening followed by Xpert MTB/RIF [Xpert] testing) is insufficiently sensitive and results in unnecessary Xpert testing.

Objectives: To evaluate whether novel ICF algorithms combining C-reactive protein (CRP)-based screening with urine Determine TB-LAM (TB-LAM), sputum Xpert, and/or sputum culture could improve ICF yield and efficiency.

Methods: We compared the yield and efficiency of novel ICF algorithms inclusive of point-of-care CRP-based TB screening and confirmatory testing with urine TB-LAM (if CD4 count ≤100 cells/μl), sputum Xpert, and/or a single sputum culture among consecutive people living with HIV with CD4 counts less than or equal to 350 cells/μl initiating antiretroviral therapy in Uganda.

Measurements and main results: Of 1,245 people living with HIV, 203 (16%) had culture-confirmed TB including 101 (49%) patients with CD4 counts less than or equal to 100 cells/μl. Compared with the current ICF algorithm, point-of-care CRP-based TB screening followed by Xpert testing had similar yield (56% [95% confidence interval, 49-63] vs. 59% [95% confidence interval, 51-65]) but consumed less than half as many Xpert assays per TB case detected (9 vs. 4). Addition of TB-LAM did not significantly increase diagnostic yield relative to the current ICF algorithm but provided same-day diagnosis for 26% of TB patients with advanced HIV. Addition of a single culture to TB-LAM and Xpert substantially improved ICF yield, identifying 78% of all TB cases.

Conclusions: Point-of-care CRP-based screening can improve ICF efficiency among people living with HIV. Addition of TB-LAM and a single culture to Xpert confirmatory testing could enable HIV programs to increase the speed of TB diagnosis and ICF yield.

Keywords: C-reactive protein; intensified case finding; screening; tuberculosis; urine lipoarabinomannan.

Figures

Figure 1.

Patient flow diagram. The diagram conforms to the Standards for the Reporting of Diagnostic Accuracy Studies 2015 guidelines for patient flow diagrams. *Outdated CD4 count was defined as CD4 count measured ≥3 months before study enrollment and antiretroviral therapy initiation. †Active TB was defined as at least one sputum culture positive for Mtb in reference to two liquid cultures. ‡Liquid culture result from the first sputum specimen collected. CRP = C-reactive protein; Mtb = Mycobacterium tuberculosis; POC = point-of-care; TB = tuberculosis.