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.

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 *Outdated CD4 count was defined as CD4 count measured ≥3 months before study enrollment and antiretroviral therapy initiation.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.