Fetal and Pediatric Pathology, 33:123–125, 2014

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ISSN: 1551-3815 print / 1551-3823 online
DOI: 10.3109/15513815.2013.878010

LETTER TO THE EDITOR

The Sensitivity of T-SPOT.TB Assay in Diagnosis

of Pediatric Tuberculosis

Xinfeng Wang,1 Yanhua Wu,1 Maoshui Wang,1 and Yunshan Wang2

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1
Shandong Provincial Chest Hospital, Lab Medicine, Jinan, China; 2 Jinan Central Hospital
Affiliated to Shandong University, Medical Research and Laboratory Diagnostic Center,
Jinan, China

This study was performed aiming to evaluate the sensitivity of T-SPOT.TB assay in diagnosis of pe-
diatric TB and investigate the association between age and results of T-SPOT.TB assay. Between
March 2012 and September 2013, 102 patients, who aged ≤15 years old, were enrolled in this ret-
rospective study and then were grouped into three age categories: Group 1, aged ≤2 years; Group
2, aged 3 to 12 years; and Group 3, aged 13 to 15 years. The χ 2 test was used to compare the sensi-
tivities of T-SPOT.TB between groups with different ages. The overall sensitivity of T-SPOT.TB assay
For personal use only.

was 58.8% (95% confidence interval: 49.1–67.9%) and low in diagnosis of pediatric TB. Although
the sensitivities varied in the three groups, the difference did not reach statistical significance
(p > 0.05). Therefore, in high burden countries, T-SPOT.TB assay wasn’t accurate in diagnosis of
pediatric TB, and age was not associated with the results of T-SPOT.TB
Keywords: Age, pediatric tuberculosis, sensitivity, T-SPOT.TB

DEAR EDITOR,
According to World Health Organization (WHO) estimates, about 1 million children
annually develop tuberculosis (TB) worldwide, accounting for about 11% of all TB
cases. Pediatric TB is often regarded as unimportant in the epidemiology of TB be-
cause > 95% of pediatric patients with TB are sputum smear negative and therefore
do not contribute to the immediate spread of the disease. Considering the fact that
children contribute a significant proportion to the global TB disease burden and suffer
severe TB-related morbidity and mortality is growing, Accurate and timely diagnosis
is very necessary and crucial to control and treat pediatric TB.
Diagnostic approaches relying on symptoms, chest radiographs, tuberculin skin
tests (TST) or cultures all have particular challenges within the pediatric population.
Interferon gamma release assays (IGRAs) are in vitro immunologic diagnostic tests
used to identify Mycobacterium TB (M.TB) infection. One such assay is an Enzyme-
linked immunosorbent spot (ELISpot) assay, commercially known as T-SPOT.TB. Meta
analysis showed that T-SPOT.TB assay was superior, in comparison with the TST, for
detecting confirmed active TB disease and latent TB infection [1, 2]. T-SPOT.TB assay
has been described from some pediatric studies in low TB prevalence countries [3, 4].
Because T-SPOT.TB cannot distinguish between latent infection and active TB disease,

Received 10 November 2013; Revised 26 November 2013; accepted 2 December 2013.

Address correspondence to Mr Maoshui Wang, Shandong Provincial Chest Hospital, Lab
Medicine, 46#, Lishan Road, Jinan 250013, China. E-mail: wangmaoshui@gmail.com


  X. Wang et al.

so defining its’ role in high burden TB countries is very useful for diagnosis of pediatric
TB. In the past few years, much research had discovered that age was positively corre-
lated with positive T-SPOT.TB results in diagnosis of pediatric latent TB [5–7]. So, it de-
served our effort to investigate the association between age and results of T-SPOT.TB
assay in diagnosis of pediatric TB. Based on these above problems, in this study, we
aimed to evaluate the sensitivity of T-SPOT.TB assay in diagnosis of pediatric TB and
investigate the association between age and results of T-SPOT.TB assay.
The protocol was approved by the Ethical Committee of Shandong Provincial Chest
Hospital, written informed consent was not required because of the retrospective na-
ture of the investigation. Between March 2012 and September 2013, patients who aged
≤15 years old were enrolled in this study. These patients were suspected TB, and T-
SPOT.TB assay (Oxford Immunote Ltd., Oxford, UK) was employed to identify M.TB
infection in these patients. Pediatric TB patients were diagnosed based on history of
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TB contact, clinical symptoms, chest X-ray examination, TST, acid-fast bacilli detec-
tion (Auramine O stain), mycobacterial culture, TB-PCR and histopathologic findings
compatible with TB (e.g., caseating granulomas). The typical symptoms included fever
(>38◦ C) for 14 days, anorexia, weight loss or failure to thrive, chronic and unremitting
cough (>3 weeks), a response to antituberculous medications revealed by improve-
ment of clinical symptoms and chest radiograph [8].
In this retrospective study, 102 pediatric TB patients were enrolled and then were
grouped into three age categories: Group 1, aged ≤ 2 years; Group 2, aged 3 to 12 years;
and Group 3, aged 13 to 15 years. Table 1 presents mean age, sex and results of T-
SPOT.TB. Statistical analysis was carried out using SPSS 17.0 software. The χ 2 test was
For personal use only.

used to compare the sensitivities of T-SPOT.TB between groups with different ages.
p < 0.05 was considered as statistically significant.
Of 102 pediatric TB patients (21 culture confirmed cases, 6 histological exami-
nation confirmed cases and the remaining were clinical diagnosed), 29 cases were
pulmonary TB; 11 tuberculous pleurisy; 7 tuberculous meningitis; 14 pulmonary TB
combined extra-pulmonary TB, 18 tuberculous lymphadenitis, 6 bone TB, 17 other
TB diseases. The overall sensitivity of T-SPOT.TB assay was 58.8% (95% confidence
interval: 49.1–67.9%). The sensitivities were as follows: 72.4% for pulmonary TB; 81.8%
for tuberculous pleurisy; 57.1% for tuberculous meningitis; 71.4% for pulmonary TB
combined extra-pulmonary TB; 38.9% for tuberculous lymphadenitis; 16.7% for
bone TB; and 47.1% for other TB diseases. These data showed that the sensitivity
of T-SPOT.TB assay in pediatric TB was low. Therefore, in high burden countries,
T-SPOT.TB assay wasn’t accurate in diagnosis of pediatric TB.
χ 2 test was applied to compare the sensitivity of T-SPOT.TB assay between different
age groups, although the sensitivities varied in the three groups, the difference did not
reach statistical significance (p > 0.05). Age should not be considered to be associated
with the result of T-SPOT.TB. Usually, age was positively correlated with TB exposure
time or the chance to get TB infection in high TB burden countries. A report showed

Table 1. Characteristics of pediatric TB patients.

T-SPOT.TB
Age (years, Sex
Group Mean ± SD) (male) Negative Positive Sensitivity (%, 95% CI)
Group 1 1.19 ± 0.75 20 10 18 64.3 (45.8,79.3)
Group 2 7.98 ± 2.77 25 23 21 47.7 (33.8,62.1)
Group 3 14.13 ± 0.82 19 9 21 70.0 (52.1,83.3)
Total 7.93 ± 5.26 64 42 60 58.8 (49.1,67.9)
SD, standard deviation; CI, confidence interval.

Fetal and Pediatric Pathology

 Letter to the Editor 

that the latent TB infection prevalence (LTBI) rate increased with age, the maximum
rates of change in LTBI prevalence being 4.4% per year in males and 3.7% per year in
females [9]. Considering the role of T-SPOT.TB assay in latent TB infection, the associ-
ation between age and positive T-SPOT-TB results are apparent.
In closing, T-SPOT.TB assay wasn’t accurate in diagnosis of pediatric TB and there
was no direct evidence that supporting age was associated with the result of T-
SPOT.TB. Although age positively correlated with positive T-SPOT.TB results, it cannot
simply be concluded that there is an association between age and results of T-SPOT.TB.
LTBI prevalence increasing with age may lead to an unacceptable conclusion.

Declaration of Interest
The authors report no conflicts of interest. The authors alone are responsible for the
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content and writing of the article.

This work was supported in part by a grant from the Health Department of Shan-
dong Province (NO.2011HZ085); in part by a grant from the Science and Technology
Department of Jinan (NO.201303043).

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