Which factors predict treatment initiation among individuals with negative TB result?

Several factors, including male sex and reported cough, influence the decisions by clinicians to initiate tuberculosis (TB) treatment among individuals who receive a negative result on an initial bacteriological test for TB, reports a study.

On the other hand, clinicians are less likely to treat without a positive test result when using more sensitive, PCR-based diagnostics, according to the researchers.

This systematic review and individual patient data meta-analysis involved studies conducted between 2010 and December 2022, particularly trials or cohort studies that enrolled individuals evaluated for TB in routine settings. Participants were assessed based on clinical examination and routinely used diagnostics and were followed for ≥1 week after the initial test result.

The researchers identified factors associated with treatment initiation following a negative result on an initial bacteriological test (eg, sputum smear microscopy [SSM], Xpert MTB/RIF) using hierarchical Bayesian logistic regression.

Clinicians were more likely to initiate TB treatment in the presence of the following factors: male sex (adjusted odds ratio [aOR], 1.61, 95 percent confidence interval [CI], 1.31–1.95), history of prior TB (aOR, 1.36, 95 percent CI, 1.06–1.73), reported cough (aOR, 4.62, 95 percent CI, 3.42–6.27), reported night sweats (aOR, 1.50, 95 percent CI, 1.21–1.90), and having HIV infection but not on antiretroviral therapy (aOR, 1.68, 95 percent CI, 1.23–2.32). [PLoS Med 2025;22:e1004502]

In contrast, clinicians were less likely to initiate treatment for individuals testing negative with Xpert (aOR, 0.77, 95 percent CI, 0.62–0.96) compared with SSM. A negative result on Xpert Ultra also correlated with lower treatment initiation rates compared with SSM, albeit not reaching statistical significance.

In secondary analyses, longer duration of cough (particularly cough persisting for over 2 weeks) and the presence of an abnormal chest X-ray were positively associated with TB treatment initiation. Of note, the odds of treatment initiation declined over the years, controlling for other factors. The reason for making these treatment decisions was not assessed due to the absence of data.

“Understanding these factors will allow for a more nuanced interpretation of the data describing the impact of introducing new TB diagnostics,” the researchers said. [Lancet Infect Dis 2015;15:16-17; Eur Respir J 2014;44:1366-1369; Nature 2015;528:S60-67]

Furthermore, this knowledge “can inform efforts to refine clinical diagnostic algorithms, determine the appropriate balance between sensitivity and specificity when revising diagnostic approaches, and improve the overall performance of TB case detection,” they added. [PLoS ONE 2020;15:e0228669]

Limitations

This study has several limitations. First, the researchers failed to analyse all factors that potentially inform clinician decision-making because of differences in the covariates recorded in the data sets. Second, patients aged under 18 years were excluded from the analysis.

Third, only studies performed under routine clinical conditions were included. Thus, “it is possible that the behaviour of clinicians performing TB diagnosis could have been influenced by their participation in clinical research,” the researchers said.

Fourth, access to additional evidence describing why clinicians made the decisions they did was not available. Finally, clinical diagnosis decisions were not compared with culture results that subsequently became available.