Avoiding the effect of BCG vaccination in detectingMycobacterium tuberculosisinfection with a blood test

Abstract

Bacille Calmette-Guérin (BCG) vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection (LTBI).The TST was compared with a Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot (ELISPOT) assay during an outbreak of MTB infection at a police academy in Germany.Participants were grouped according to their risk of LTBI in close (n536) or occasional (n5333) contacts to the index case. For the TST, the positive response rate was 53% (19 out of 36) among close and 16% (52 out of 333) among occasional contacts. In total, 56 TST-positive contacts (56 out of 71578.9%) and 27 TST-negative controls (27 out of 29859.1%) underwent ELISPOT testing. The odds ratio (OR) of a positive test result across the two groups was 29.2 (95% confidence interval (CI) 3.5-245.0) for the for the TST with a 5 mm cutoff. Of 369 contacts, 158 (42.8%) had previously received BCG vaccination. The overall agreement between the TST and the ELISPOT was low, and positive TST reactions were confounded by BCG vaccination (OR 4.8 (95% CI 1.3-18.0)). In contrast, use of a 10-mm induration cut-off for the TST among occasional contacts showed strong agreement between TST and ELISPOT in nonvaccinated persons.In bacille Calmette-Guérin-vaccinated individuals, the Mycobacterium tuberculosis-specific enzyme-linked immunospot assay is a better indicator for the risk of latent tuberculosis infection than the tuberculin skin test.KEYWORDS: Contact tracing, early secretory antigenic target 6, enzyme-linked immunospot assay, interferon-c, latent tuberculosis infection, tuberculosis A pproximately one-third of mankind is currently infected with Mycobacterium tuberculosis (MTB), causing significant morbidity and mortality with .2 million deaths?yr -1 [1]. Tuberculosis (TB) control programmes aim to decrease the incidence of TB by interruption of the transmission of MTB. Contact tracing and treatment of individuals with latent TB infection (LTBI) are the key components of TB control programmes. In addition, other important key components of TB control are the improvement of case finding among persons presenting with symptoms of TB, especially in HIV-infected individuals, by providing better access to quality-assured TB sputum microscopy as well as the Directly Observed Therapy Short-Course strategy in TB treatment. The latter achieves higher cure rates by an uninterrupted supply of antituberculotic drugs in a standardised short-course chemotherapy under direct observation [2].By applying classical epidemiological and molecular strain-typing techniques, population-based studies have recently revealed a high frequency of transmission of MTB, even in countries with a low TB incidence [3][4][5][6][7]. The tuberculin skin test (TST) introduced by Mantoux has been widely used as a screening test to identify individuals with LTBI. In screening for LTBI, the predictive value of a positive TST result (positive predictive value (PPV)) is the probability that a contact with a positive TST result is tru...

LTBI: latent tuberculosis infection or lasting immune responses toM. tuberculosis? A TBNET consensus statement

“…In a number of contact investigations, substantially fewer BCG unvaccinated subjects had positive IGRA results compared with positive tuberculin skin test results [74,86,[89][90][91][92][93][94][95][96][97][98][99]. Comparability between the two IGRAs was generally good, whereas the agreement between tuberculin skin test and IGRA was poor, owing to false-positive tuberculin skin test results in BCG-vaccinated subjects or, based on studies among BCG unvaccinated subjects, to lower sensitivity of IGRA for detection of infections acquired in the past.…”

Cost-effectiveness of interferon-γ release assay testing for the treatment of latent tuberculosis

“…The effectiveness and cost-effectiveness of these programmes are strongly affected by the accuracy of identifying truly infected individuals who have a risk of developing future disease. Owing to the limited sensitivity and specificity of the tuberculin skin test (TST), it follows that the current cost-effectiveness of screening may be improved if more accurate tools are used for screening for latent tuberculosis infection (LTBI).Numerous studies screening recent contacts of infectious TB patients for LTBI using the new highly specific interferon-c release assays (IGRA) have recently been published [2][3][4][5][6][7], but no study has produced cost-effectiveness data. In two papers [8,9] the way in which IGRA can be used for cost-saving in initial screening has been discussed.…”

“…Numerous studies screening recent contacts of infectious TB patients for LTBI using the new highly specific interferon-c release assays (IGRA) have recently been published [2][3][4][5][6][7], but no study has produced cost-effectiveness data. In two papers [8,9] the way in which IGRA can be used for cost-saving in initial screening has been discussed.…”

Rapid diagnosis of Mycobacterium tuberculosis infection in children using interferon-gamma release assays (IGRAs)

“…9,14 -16 Several studies performed primarily in adults indicate that both tests are more specific than the TST and are not confounded by previous BCG vaccination or by infection with most nontuberculous bacteria. 9,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Powell et al 30 recommend that with unusual IFN-␥ measurements, not only should the QFT-G and QFT-GIT be repeated with another blood sample to avoid erroneous diagnosis of M. tuberculosis infection and interpreted with caution if they recur but also encourage more meticulous recognition of these unusual IFN-␥ measurements that may be a predictive marker of inaccurate results. In the study by Pareek et al, 24 the use of screening by QFT-GIT in the UK for latent TB in immigrant populations was found to be cost-effective, thereby preventing substantial numbers of future cases of active TB.…”