Factors associated with tuberculosis treatment initiation among bacteriologically negative individuals evaluated for tuberculosis: An individual patient data meta-analysis

Abstract

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative.

Methods and findings: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies, participants were evaluated based on clinical examination and routinely used diagnostics and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy (SSM), Xpert MTB/RIF). Multiple factors were positively associated with treatment initiation: male sex [adjusted odds ratio (aOR) 1.61 (1.31, 1.95)], history of prior TB [aOR 1.36 (1.06, 1.73)], reported cough [aOR 4.62 (3.42, 6.27)], reported night sweats [aOR 1.50 (1.21, 1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23, 2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62, 0.96)] compared to smear microscopy and declined in more recent years. We were not able assess why clinicians made treatment decisions, as these data were not available.

Conclusions: Multiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.

Fig 1. Identification of studies and data to include in the meta-analysis.

Fig 2. Odds ratios of TB treatment initiation following negative diagnostic test result: Secondary analysis for data sets including duration of symptoms for cough, fever, and night sweats*

.* Reference group: Age 18–30 years old, female sex, no history of prior TB, no reported cough, no reported fever, no reported night sweats, HIV–negative, tested negative with SSM. Blue symbols signify ORs >1.0, red symbols signify ORs <1.0. ART, antiretroviral therapy; OR, odds ratio; SSM, sputum smear microscopy; TB, tuberculosis.