T Cell–Based Tracking of Multidrug Resistant Tuberculosis Infection after Brief Exposure

Abstract

Molecular epidemiology indicates significant transmission of Mycobacterium tuberculosis after casual contact with infectious tuberculosis cases. We investigated M. tuberculosis transmission after brief exposure using a T cell-based assay, the enzyme-linked-immunospot (ELISPOT) for IFN-gamma. After childbirth, a mother was diagnosed with sputum smear-positive multidrug-resistant tuberculosis. Forty-one neonates and 47 adults were present during her admission on the maternity unit; 11 weeks later, all underwent tuberculin skin testing (TST) and ELISPOT. We correlated test results with markers of exposure to the index case. The participants, who were asymptomatic and predominantly had no prior tuberculosis exposure, had 6.05 hours mean exposure (range: 0-65 hours) to the index case. Seventeen individuals, including two newborns, were ELISPOT-positive, and ELISPOT results correlated significantly with three of four predefined measures of tuberculosis exposure. For each hour sharing room air with the index case, the odds of a positive ELISPOT result increased by 1.05 (95% CI: 1.02-1.09, p = 0.003). Only four adults were TST-positive and TST results did not correlate with exposure. Thus, ELISPOT, but not TST, suggested quite extensive nosocomial transmission of multidrug-resistant M. tuberculosis after brief exposure. These results help to explain the apparent importance of casual contact for tuberculosis transmission, and may have implications for prevention.

Use of a T-cell-based test for detection of tuberculosis infection among immunocompromised patients: Table 1—

“…The current authors' tentative conclusions are supported by the substantial body of literature demonstrating that the T-SPOT.TB TM test result correlates more closely with exposure [10][11][12][13][14], is more sensitive than the TST [7,[15][16][17][18] and is not prone to cross-reaction to BCG and most nontuberculous mycobacteria [11,[19][20].…”

O desafio da tuberculose na faixa etária pediátrica frente a novas técnicas diagnósticas

“…18,68,86 The ELISPOT, which is commonly used in Europe, has been approved by the FDA in the United States in July 2008.…”

“…Table 1 shows a comparison between the TST and the IGRAs. Richeldi et al 18 commented that the fact that The literature has shown that undetermined results were found in up to 11% of the patients tested with the QFT-G, and this finding must be associated with the small number of immunosuppressed patients included in these studies. [98][99][100] Ferrara et al 79 found high rate of undetermined results Other studies have shown that the prevalence of positive ELISPOT results was higher than that found using the TST, mainly in immunosuppressed patients.…”

“…109 Several studies involving children have demonstrated that the ELISPOT has higher sensitivity than the TST in the diagnosis of latent infection. 18,19,110 Due to the fact that the ELISPOT correlates better with different patterns of exposure to TB than the TST, it is possible to conclude that the ELISPOT has better sensitivity than the TST. However, longitudinal studies are needed to confirm the actual higher sensitivity of the IGRAs.…”

“…11,[15][16][17] These assays have good sensitivity and specificity for the diagnosis of TB, presenting advantages in comparison with the TST, mainly in patients with some degree of immunosuppression. [18][19][20][21] Early diagnosis and treatment of tuberculosis infection, avoiding progression to disease, are challenges that need to be overcome so that worldwide control of TB can be achieved. 22 New diagnostic methods will be welcome, mainly when their aim is to aid the diagnosis of TB in special groups like children and immunosuppressed patients.…”