Contact investigation in a primary school using a whole blood interferon-gamma assay

https://doi.org/10.1016/j.jinf.2009.02.019Get rights and content

Summary

Objectives

To evaluate the usefulness of QuantiFERON®-TB Gold (QFT-G) for children.

Methods

Students in a primary school exposed to a tuberculosis patient were investigated using the tuberculin skin test (TST), chest X-ray examination and sequential QFT-G tests.

Results

The first QFT-G test was conducted one month after the end of exposure for 308 of the 313 children, with 6 (1.9%) positive. TST results were obtained from 306 of the students at 2 months after exposure, and 200 (65.4%) had induration ≥5 mm. A second QFT-G test, a further month later, and a third QFT-G test, six months after exposure, found an additional 2 positive and one weakly positive, respectively. Overall, the rate of QFT-G positivity was 9.8% (4/41) for close contact children (≥90 h exposure), significantly higher than for casual contacts (≤18 h exposure; 1.8%, 5/272; p = 0.020), whereas there was no significant difference in TST positive rates (p = 0.078).

Conclusions

These data suggest that QFT-G has the same performance characteristics in BCG vaccinated children as it does in adults. The observation that none of the 297 students who were QFT-G negative had developed active TB after 3 years of follow-up suggests that QFT-G has a very high negative predictive value.

Introduction

Tuberculosis (TB), which is caused by infection with Mycobacterium tuberculosis complex (MTB), is still a major human health problem, especially in developing countries.1 It has been estimated that third of the world's population is latently infected with MTB,2 providing a large reservoir for future transmission. In developed countries, contact investigations are a major component of TB control activities, with those identified as having latent TB infection (LTBI) generally indicated for preventive chemotherapy.3, 4 Until recently, the tuberculin skin test (TST) and chest X-ray examination have been the main tools used for contact investigations. However, chest X-ray examination does not detect LTBI. Moreover, the TST is known to be confounded by prior BCG vaccination or reactivity to non-tuberculous mycobacteria (NTM) due to cross-reactivity between the PPD used for the TST and antigens of BCG and NTM.5 Thus, identification of contacts with LTBI has been problematic, especially in countries where BCG vaccination is widely conducted.

Identification of the highly specific RD1 region of the MTB genome has enabled development of new diagnostics for MTB infection, interferon-gamma release assays (IGRAs), which distinguish MTB infection from effects of prior BCG vaccination or reactivity to the majority of NTM.6 The clinical performance of one of these tests, QuantiFERON®-TB Gold (QFT-G), has been extensively investigated by our group and others,7, 8, 9, 10, 11, 12, 13 and QFT-G is now routinely used for contact investigations in several countries including Japan. Although there have been some studies reporting good performance of QFT-G in children,14, 15, 16, 17, 18 available data in this population group are limited. In the present study, we used the QFT-G test in a contact investigation in a primary school to further evaluate its usefulness in children.

Section snippets

The index case

The index case was a 46 years old male teacher in a primary school. Feeling discomfort in his throat in September 2005 and developing a severe cough in early October 2005, he initially visited an otolaryngologist, but TB was not detected. On 17 November he attended a clinic after producing sputum containing blood and chest X-ray revealed cavitary lesions in his lung's left middle quadrant. Due to suspicion of pulmonary TB, a CT scan was performed and based on the findings he was admitted to a

Contact investigation using the TST

TST results were available for 306 of the 313 students, with 200 (65.4%) having induration greater than or equal to 5 mm. Using a cut-off of 10 mm, 90 of the 306 (29.4%) children were TST positive. Fig. 1 shows the distribution of TST induration of all subjects. There was no significant difference in the rate of TST positivity using a cut-off of 5 mm for those children in the close contact group (20/38: 52.6%) as compared with the casual contact group (180/268: 67.2%; Pearson's chi-square test, p = 

Discussion

IGRAs are now increasingly used in several industrialized countries. Although both QFT-G and an ELISpot-based test (T-SPOT®.TB), are being used for children,14, 15, 16, 17, 18, 21, 22 available data are still limited, especially in those of younger age. In this study we used the QFT-G test in addition to conventional methods for evaluating children during an MTB contact investigation in a primary school. The rate of positive results for the QFT-G test in the close contact group was

Acknowledgment

We are grateful to the staff in public health centers for providing these data. This study was partly supported by the donation from a charitable person in Shiga prefecture, Japan.

References (34)

  • T. Mori et al.

    Specific detection of tuberculosis infection with an interferon-gamma based assay using new antigens

    Am J Respir Crit Care Med

    (2004)
  • N. Harada et al.

    Usefulness of a novel diagnostic method of tuberculosis infection, QuantiFERON®TB-2G, in an outbreak of tuberculosis

    Kekkaku

    (2004)
  • T. Mori et al.

    Cost-effectiveness analysis of QuantiFERON-TB 2nd generation used for detection of tuberculosis infection in contact investigations

    Kekkaku

    (2005)
  • N. Harada et al.

    Screening for tuberculosis infection using whole-blood interferon-gamma and Mantoux testing among Japanese healthcare workers

    Infect Control Hosp Epidemiol

    (2006)
  • K. Higuchi et al.

    Use of QuantiFERON-TB Gold to investigate tuberculosis contacts in a high school

    Respirology

    (2007)
  • T. Mori et al.

    Waning of the specific interferon-gamma response after years of tuberculosis infection

    Int J Tuberc Lung Dis

    (2007)
  • T.G. Connell et al.

    QuantiFERON-TB Gold: state of the art for the diagnosis of tuberculosis infection?

    Expert Rev Mol Diagn

    (2006)
  • Cited by (31)

    • Predictive value of interferon-γ release assays and tuberculin skin testing for progression from latent TB infection to disease state: A meta-analysis

      2012, Chest
      Citation Excerpt :

      Five studies used “in-house” tests,15–19 four QFT-G,13,20–22 14 QFT-GIT,14,23–35 and seven T-SPOT.TB.13,14,36–40 Fourteen studies were contact investigations,14–22,25–27,33,34 one of which was retrospective by study design.22 Five studies included HIV-positive individuals,24,32,36,37,40 whereas six studies were concerned exclusively with children or adolescents.16,20,21,29,31,34

    • A current review of infection control for childhood tuberculosis

      2011, Tuberculosis
      Citation Excerpt :

      This strategy was more cost-effective than screening HCWs by either TST or IGRA alone in one study.41 While IGRAs have yet to be studied for in-hospital contact investigations for exposed children, at least one study demonstrated the utility of IGRAs for school-based contact investigations in a BCG-immunized population.42 The scenario of the older adolescent presenting with weight loss, fever, and hemoptysis who has a cavitary lung lesion on radiograph both infrequently is seen and is less of an infection control dilemma, as the indication for isolation should be obvious.

    • Immune-based diagnostics for TB in children: What is the evidence?

      2011, Paediatric Respiratory Reviews
      Citation Excerpt :

      The IGRA measures the T-cell response to antigens encoded within the region of difference-1 (RD1) of the M. tuberculosis genome, which are absent from all BCG strains and most NTM.8 Many national guidelines in low-incidence countries have already approved their use in conjunction with the TST for the diagnosis of TB in children.9–13 Several free online resources are now available.

    View all citing articles on Scopus
    1

    Present address: Health and Welfare Center, Asao Ward Office, Kawasaki City, Kanagawa, Japan.

    2

    Present address: Kaken-Hospital, Institute of Chemotherapy, Kohnodai, Ichikawa City, Chiba, Japan.

    3

    Present address: Health and Welfare Center, Saiwai Ward Office, Kawasaki City, Kanagawa, Japan.

    4

    Present address: Health and Welfare Bureau, Kawasaki City, 1, Miyamoto-cho, Kawasaki Ward, Kawasaki City, Japan.

    View full text