Is the sensitivity of T-SPOT.TB impaired among very young children?
In contrast to what has been published about the superior sensitivity
of the T-SPOT.TB assay for the diagnosis of tuberculosis among young
children [1,2], Nicol et al drew our attention to the possibility that the
T-SPOT.TB assay might have impaired sensitivity for very young children,
for whom the assay should not be used for excluding active
tuberculosis[3]. There were three major findings in their study: (1) the
sensitivity of T-SPOT.TB was significantly lower than the tuberculin skin
test (TST) when a subgroup of 58 children with definite or probable
tuberculosis were considered (40% versus 52%, respectively, P=0.046); (2)
a very low proportion [3% (95% CI: <0.0001%–18%)] of positive T-SPOT.TB
results among infants aged 12 months or less; and (3) a significant
increase in the proportion of positive T-SPOT.TB results with age (P <
0.0001 by chi-squared test for trend).
However, the study was carried out on recently BCG-vaccinated
children in a community with high risk of tuberculosis exposure. No
randomly selected asymptomatic controls were included to allow for BCG
effect or latent tuberculosis infection. Only 10 subjects had unequivocal
bacteriologically confirmed disease. With these intrinsic limitations, the
findings might be interpreted rather differently.
First, their finding of a lower sensitivity of T-SPOT.TB in
comparison with that of TST among children with definite or probable
tuberculosis actually failed to reach statistical significance (P for chi-
squared test = 0.192 rather than 0.046). While a sensitivity of only 40%
for T-SPOT.TB in contrast to a high sensitivity above 80% shown by other
pediatric studies[1,2] may be explained by less severe disease in the
community setting, the lack of bacteriological confirmation in over 80% of
cases in Nicol’s study[3] might be the principal reason for an apparently
reduced sensitivity. Second, the proportion of positive T-SPOT.TB results
among infants would have been 1/4 (25%) rather than 1/30 (3%) had Nicol et
al restricted their analysis to the 58 children with definite or probable
tuberculosis. Third, the significant increase in the proportion of
positive T-SPOT.TB results with age was probably due to the inclusion of a
large number of children with possible or no tuberculosis. If analysis had
been restricted to the 58 children with definite or probable tuberculosis,
there would probably be insufficient evidence for suggesting an impaired
sensitivity of T-SPOT.TB among very young children.
Although evidence for substantiating the superiority of the T-SPOT.TB
assay among very young children is scarce, there is probably insufficient
evidence to discourage its use among very young children, especially when
they have been BCG-vaccinated or there is coexisting impairment in the
host immunity that may render TST insensitive despite a low cut-off
value[1].
Kwok-Chiu Chang,
Chi-Chiu Leung
Tuberculosis & Chest Service, Centre for Health Protection,
Department of Health, Hong Kong
References
1. Liebeschuetz S, Bamber S, Ewer K, Deeks J, Pathan AA, Lalvani A.
Diagnosis of tuberculosis in South African children with a T-cell-based
assay: a prospective cohort study. Lancet 2004;364:2196-203.
2. Detjen AK, Keil T, Roll S, et al. Interferon-gamma release assays
improve the diagnosis of tuberculosis and nontuberculous mycobacterial
disease in children in a country with a low incidence of tuberculosis.
Clin Infect Dis 2007;45:322-8.
3. Nicol MP, Davies MA, Wood K, et al. Comparison of T-SPOT.TB assay
and tuberculin skin test for the evaluation of young children at high risk
for tuberculosis in a community setting. Pediatrics 2009; 123:38-43.
Conflict of Interest:
None declared
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