Children with negative TB skin test at high risk for mortality

By Ingrid Grasmo, MedWire Reporter

Children with clinical signs of tuberculosis (TB) but with a negative tuberculin skin test (TST) result should not have treatment delayed, suggest study findings showing that false-negatives are common and associated with high mortality.

The World Health Organization guidelines for childhood TB allow for a measure of flexibility and clinical judgment in making the diagnosis, yet attempts to make a bacteriologic diagnosis in children are often inadequate. Children who do not meet traditional diagnostic criteria such as smear positivity and positive TST often receive treatment when it is already too late, the study researchers note.

"A negative TST should not supplant clinical judgment when clinical and radiographic features suggest TB," say Peter Drobac (Brigham and Women's Hospital, Boston, Massachusetts, USA) and colleagues.

The researchers used patient health records to examine factors associated with in-hospital death among 2392 children, aged 0‑14 years, who were hospitalized with TB at a Peruvian referral hospital during 1973‑1997.

In total, 82.2% of children were ill for over 4 weeks at the time of admission and had a subsequent median hospital stay of 70 days. Abnormal findings on chest auscultation were seen in 88.6% of children, with 51.6% showing signs of respiratory distress. Pulmonary disease was seen in 42% of children, with 76.5% showing both pulmonary and extrapulmonary manifestations.

TB was diagnosed in 53.9% of children, including 41.2% with a positive acid-fast smear, 29.6% with positive mycobacterial culture, and 5.1% with histopathologic findings consistent with TB.

Negative responses to TST were seen in 41.5% and 43.8% of children with and without confirmed TB, and were more prevalent among children who were underweight on admission compared with normal-weight children (55.1 vs 44.9%).

In all, 11.1% of children died from TB, with mortality highest among children aged less than 1 year (46.9%), decreasing to 3.2% by the age of 14 years.

Children with both pulmonary and extrapulmonary disease had higher rates of mortality (17.0%) than those with pulmonary (7.4%) or extrapulmonary (6.9%) disease alone.

A negative TST was associated with a 3.01-fold increased risk for death, as was younger age (5‑9 years; hazard ratio [HR]=2.22), respiratory distress (HR=1.40), altered mental status (HR=3.25), and peripheral edema (HR=1.97).

Treatment regimens containing rifampicin reduced the risk for mortality by 53% relative to those not containing the drug.

"Given that most cases of childhood TB are managed in community-based settings, our findings may help identify children requiring more aggressive care and hospitalization," conclude the authors in Pediatrics.

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