PPD skin test positivity and in-hospital mortality across age groups in non-HIV tuberculous meningitis: a retrospective cohort study.

BACKGROUND

Purified Protein Derivative (PPD) skin test reactivity reflects cell-mediated immune response to Mycobacterium tuberculosis. Evidence regarding the prognostic association of PPD reactivity in TBM, particularly its variation across age groups, remains limited.

METHODS

We conducted a single-center retrospective cohort study of consecutive non-HIV TBM patients. Firth's penalized logistic regression was used to estimate the association between PPD status and in-hospital mortality using fixed covariate sets selected on clinical grounds. Entropy balancing was used as a complementary covariate-balancing analysis. Age-related heterogeneity in the PPD-mortality association was evaluated on multiplicative and additive scales and explored using restricted cubic splines (RCS). Discrimination, calibration, and exploratory decision-curve net benefit were summarized using the area under the receiver operating characteristic curve (AUC), optimism-corrected AUC, Brier score, calibration intercept and slope, and decision curve analysis.

RESULTS

Among 1,574 patients, 187 (11.9%) died during hospitalization. In the fixed clinical model, there was no clear evidence that PPD positivity was associated with mortality in the full cohort (OR 1.30, 95% CI 0.74-2.19) or among adults (OR 0.68, 95% CI 0.31-1.34). Among 211 children, 9 of 25 PPD-positive children and 13 of 186 PPD-negative children died. The age- and diagnostic-category-adjusted pediatric estimate was OR 7.20, 95% CI 2.70-18.94; however, it was based on only 22 pediatric deaths and should be considered hypothesis-generating. The multiplicative interaction OR for adults versus children was 0.08 (95% CI 0.02-0.28), and the pediatric-minus-adult difference in standardized mortality-probability contrasts was 0.321 (95% CI 0.158-0.510). Full-cohort model performance was modest (AUC 0.673; optimism-corrected AUC 0.647; Brier score 0.0994). For the primary pediatric model, the E-value was 4.81 for the point estimate and 2.67 for the lower confidence-limit bound after approximate OR-to-RR conversion.

CONCLUSION

We found no clear evidence that PPD positivity was associated with in-hospital mortality in the full cohort. The pediatric association was large but imprecise and depended on nine deaths among PPD-positive children; it should be treated as an exploratory signal rather than an established age-dependent prognostic association. Multicenter studies using standardized PPD procedures, quantitative induration and testing-time data, and detailed baseline severity measures are needed to independently replicate the pediatric association.