Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak

Ewer, Katie; Deeks, Jonathan J; Álvarez, Lydia; Bryant, Gerry; Waller, Sarah; Andersen, Peter; Monk, Philip; Lalvani, Ajit

doi:10.1016/s0140-6736(03)12950-9

Cited by 557 publications

(439 citation statements)

References 27 publications

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“…Compared with the TST, research using IFNGRA indicates a high sensitivity for active tuberculosis (8)(9)(10). Positive scores in these assays have also been shown in contact studies to equate well with a history of exposure to tuberculosis (11)(12)(13).…”

Section: What This Study Adds To the Fieldmentioning

confidence: 74%

Effect of HIV-1 Infection on T-Cell–based and Skin Test Detection of Tuberculosis Infection

Rangaka¹,

Wilkinson²,

Seldon³

et al. 2007

Am J Respir Crit Care Med

185

152

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Section: What This Study Adds To the Fieldmentioning

confidence: 74%

Effect of HIV-1 Infection on T-Cell–based and Skin Test Detection of Tuberculosis Infection

Rangaka¹,

Wilkinson²,

Seldon³

et al. 2007

Am J Respir Crit Care Med

185

152

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“…Moreover, although these volunteers did not undergo a TST, all were negative by the IFN-␥ ELISPOT assay with peptides spanning the lengths of ESAT-6 and CFP10. Given that the ESAT-6-CFP10-based ELISPOT assay appears to be at least as sensitive as the TST for detecting latent M. tuberculosis infection (19,25), it is very unlikely that the responses to Rv3873, Rv3878, and Rv3879c in these unexposed donors were a result of latent M. tuberculosis infection. However, given the lack of a "gold standard" test for latent infection, this possibility cannot be completely excluded.…”

Section: Vol 72 2004 T-cell Responses To Novel M Tuberculosis Genementioning

confidence: 99%

“…Thus, there has been an intensive search for specific M. tuberculosis antigens that are not cross-reactive with BCG (3,8,27). Since humoral immune responses are generally weak in latent M. tuberculosis infection, the search for specific proteins has focused increasingly on antigens that are targets of cell-mediated immune (CMI) responses (5,19). A cocktail of a small number of such defined T-cell antigens could form the basis of new T-cell-based in vitro blood tests for M. tuberculosis infection that do not cross-react with BCG (28).…”

mentioning

confidence: 99%

Evaluation of T-Cell Responses to Novel RD1- and RD2-EncodedMycobacterium tuberculosisGene Products for Specific Detection of Human Tuberculosis Infection

et al. 2004

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The tuberculin skin test for diagnosing Mycobacterium tuberculosis infection suffers from antigenic crossreactivity of purified protein derivative with BCG, resulting in poor specificity in BCG-vaccinated populations. Comparative genomics has identified several genetic regions in M. tuberculosis and M. bovis that are deleted in M. bovis BCG. Proteins encoded in these regions will form the basis of new specific T-cell-based blood tests that do not cross-react with BCG, but only two, early secretory antigen target 6 and culture filtrate protein 10, have been studied in detail in humans. We investigated four novel gene products, encoded by RD2 (Rv1989c) and RD1 (Rv3873, Rv3878, and Rv3879c), that are absent from most or all of the vaccine strains of BCG, respectively. Sixty-seven overlapping peptides were tested in ex vivo gamma interferon enzyme-linked immunospot assays in 49 patients with culture-confirmed tuberculosis and 38 healthy BCG-vaccinated donors. Forty-five percent (95% confidence interval [CI], 31 to 57%) and 53% (95% CI, 39 to 67%) of the tuberculosis patients responded to Rv3879c and Rv3873, respectively, identifying these proteins as major M. tuberculosis T-cell antigens in humans, while 35 and 25% of the patients responded to Rv3878 and Rv1989c, respectively. Of the 38 BCG-vaccinated donors, 1 (2.6%) responded to peptides from Rv3878 and Rv3879c, 3 (7.9%) responded to Rv3873, and none responded to Rv1989c. Exclusion of cross-reactive peptides encoded in conserved motifs of Rv3873, a PPE family member, increased its specificity to 97.4%. The high specificity of Rv3879c peptides and nonconserved Rv3873 sequences, together with their moderate sensitivity in tuberculosis patients, identifies these peptides as candidates for inclusion in new T-cell-based tests for M. tuberculosis infection.Accurate diagnosis of tuberculosis (TB) infection is essential for the treatment, prevention, and control of this resurgent disease (1). Since Mycobacterium tuberculosis is often difficult to culture from patients with active TB, and impossible to culture from healthy latently infected people, an immunebased diagnostic test indicating the presence or absence of M. tuberculosis infection would be very useful for the diagnosis of active TB and screening for latent M. tuberculosis infection. The only widely used test is the century-old tuberculin skin test (TST), which has many drawbacks. Foremost among these is its poor specificity (21). This results from the broad antigenic cross-reactivity of purified protein derivative (PPD), a crude mixture of more than 200 M. tuberculosis proteins widely shared among M. tuberculosis, M. bovis Bacillus CalmetteGuérin (BCG), and most environmental mycobacteria (22). Hence, false-positive results are common in people with environmental mycobacterial exposure and previous BCG vaccination. Since most of the world's population is BCG vaccinated and since the confounding effect of BCG persists for up to 15 years after vaccination (41), this is a significant problem. Thus, there has been a...

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“…This may be because of the different characteristics of the cohort in our study. Although many reports indicate that BCG vaccination affects TST in diagnosis of TB infection Mazurek et al, 2001;Ewer et al, 2003;Pai et al, 2004), others report controversial data. Pai et al (2005) and Dogra et al (2007) showed a high concordance between TST and QuantiFERON® either in health care workers or in children in India, a highly TB endemic country, suggesting there is little influence of BCG vaccination on TST.…”

Section: Discussionmentioning

confidence: 99%

“…PPD is a mixture of mycobacterial antigens, some of which are shared between non-tuberculous mycobacteria (NTM) and Mycobacterium bovis BCG vaccine strains Lee et al, 2002). As a result, the TST is not adequate for the diagnosis of latent TB in populations with high BCG coverage and/or high-levels of NTM exposure Mazurek et al, 2001;Ewer et al, 2003;Pai et al, 2004). The sensitivity also may be low in individuals with decreased immune function (i.e., AIDS and other immunosuppressive conditions, advanced tuberculosis, malnutrition) (Liebeschuetz et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the diagnostic utility of a whole-blood interferon-γ assay for determining the risk of exposure to Mycobacterium tuberculosis in Bacille Calmette-Guerin (BCG)-vaccinated individuals

Eum

Lee

Kwak

et al. 2008

Diagnostic Microbiology and Infectious Disease

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We evaluated the utility of the "QuantiFERON®-TB Gold in tube" (QuantiFERON®) test that uses TB-specific antigens for the diagnosis of latent infection in such individuals. We also examined the correlation between the IFN-γ response to these antigens and the exposure risk to TB by evaluating antigen-specific IFN-γ release in comparison with IFN-γ release in response to PPD in three groups; medical students, nurses in a TB hospital, and TB patients. All nurses and TB patients responded to PPD whereas 79.2 % (p=0.04) and 52 % (p<0.0001) responded to QuantiFERON®, respectively. In the medical students, only 10.4 % responded to QuantiFERON® while 85.2 % were positive to PPD (p < 0.0001). There was also a significant correlation between the levels of IFN-γ production and the duration of employment in the group of nurses at the TB hospital suggesting on-going exposure in this high risk group. Thus these results demonstrate that Mycobacterium tuberculosis-specific IFN-γ release assay accurately discriminates low and high risk healthy subjects and might therefore be a useful diagnostic tool for the diagnosis of latent infection in BCG-vaccinated individuals.

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Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak

Cited by 557 publications

References 27 publications

Effect of HIV-1 Infection on T-Cell–based and Skin Test Detection of Tuberculosis Infection

Effect of HIV-1 Infection on T-Cell–based and Skin Test Detection of Tuberculosis Infection

Evaluation of T-Cell Responses to Novel RD1- and RD2-EncodedMycobacterium tuberculosisGene Products for Specific Detection of Human Tuberculosis Infection

Evaluation of the diagnostic utility of a whole-blood interferon-γ assay for determining the risk of exposure to Mycobacterium tuberculosis in Bacille Calmette-Guerin (BCG)-vaccinated individuals

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