In Children With TB, Negative Skin Test Predictive of Death

Joe Barber Jr, PhD

July 23, 2012

July 23, 2012 — A negative tuberculin skin testing (TST) result, as defined by a reaction of less than 5 mm of induration by Mantoux testing, is strongly predictive of active tuberculosis (TB)-related death in children. Treatment for TB should be administered if other signs of TB are present, irrespective of the TST result, according to the findings of a retrospective study.

Peter C. Drobac, MD, from Partners in Health and Brigham and Women's Hospital in Boston, Massachusetts, and colleagues published their findings in an article published online July 23 and in the August issue of Pediatrics.

The authors note that TST may not be a sufficient basis for confirming active TB infection. "Although [TST] is a cornerstone of diagnosis in many settings, up to 10% of immunocompetent children with culture-confirmed TB may have false-negative responses to TST," the authors write.

"Because TST status is often included in the diagnostic algorithm for childhood TB, a false-negative TST could result in harmful treatment delays."

The authors reviewed the medical records of 2392 children aged 0 to 14 years who were hospitalized with active TB at the Instituto de Salud del Niño in Lima, Peru, between January 1, 1973, and December 31, 1997. Among these children, a negative TST result was significantly associated with an increased risk for death in both univariate (hazard ratio [HR], 4.97; 95% confidence interval [CI], 3.55 - 6.96; P < .0001) and multivariate (HR, 3.01; 95% CI, 2.15 - 4.21; P < .0001) analysis.

The authors included children for whom complete data (admission date, discharge date, outcome of hospitalization) were available. The multivariate analysis was adjusted for all potential predictors of mortality, including age, sex, duration of illness, and TST result.

In total, 266 children in the cohort (11.1%) died because of active TB, and 46.9% of these children were younger than 1 year. In addition to a negative TST result, younger age (0 - 4 years: HR, 3.53; 95% CI, 2.40 - 5.18; P < .0001; 5 - 9 years: HR, 2.22; 95% CI, 1.52 - 3.24; P < .0001), altered mental status (HR, 3.25; 95% CI, 2.48 - 4.27; P < .0001), and peripheral edema (HR, 1.97; 95% CI, 1.42 - 2.73; P < .0001) were predictive of TB-related death, whereas rifampicin treatment (HR, 0.47; 95% CI, 0.33 - 0.68; P < .0001) was predictive of survival.

Limitations of the study included its retrospective nature and the inability to completely rule out selection and referral bias.

The authors suggested that their findings support the administration of TB treatment when signs of TB are present. "Our findings suggest that aggressive attempts to achieve bacteriologic diagnosis pay dividends in settings of high TB burden and that a negative TST should not supplant clinical judgment when clinical and radiographic features suggest TB," the authors write.

The authors have disclosed no relevant financial relationships.

Pediatrics. Published online July 23, 2012.

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