Quantitative T Cell Assay Reflects Infectious Load of Mycobacterium tuberculosis in an Endemic Case Contact Model

Hill, Philip C.; Fox, Annette; Jeffries, David; Jackson-Sillah, Dolly; Lugos, Moses D.; Owiafe, Patrick K.; Donkor, Simon; Hammond, Abdulrahman S.; Corrah, Tumani; Adegbola, Richard A.; McAdam, Keith P. W. J.; Brookes, Roger H.

doi:10.1086/427030

Cited by 65 publications

(46 citation statements)

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“…This corresponds to the results of other studies, in which a strong agreement between TST and ELISPOT could be seen when a diameter of 10 mm was used as cut-off from the start [29]. Thus, when the TST is performed for TB contact tracing, a TST with a cut-off of 10 mm, rather than 5 mm, as stated in the ATS/Centers for Disease Control and Prevention and current German Guidelines, should be regarded as positive in BCG-vaccinated individuals and/or occasional contacts.…”

Section: Discussionsupporting

confidence: 90%

Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test

Diel

Ernst²,

Döscher³

et al. 2006

European Respiratory Journal

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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...

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Section: Discussionsupporting

confidence: 90%

Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test

Diel

Ernst²,

Döscher³

et al. 2006

European Respiratory Journal

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“…IGRAs avoid subjective measurements, can be repeated without boosting, and eliminate the need for repeat visits and two-step testing; these features are ideal for serial testing (9)(10)(11)(12). In addition, IGRAs may actually detect recent, as compared with remote, infection, and T-cell responses may be related to bacterial burden (15)(16)(17)(18). In that case, IGRAs may be particularly well suited to detecting new infections (i.e., conversions).…”

mentioning

confidence: 99%

Serial Testing of Health Care Workers for Tuberculosis Using Interferon-γ Assay

Pai

Joshi²,

Dogra³

et al. 2006

Am J Respir Crit Care Med

254

234

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Rationale: Although interferon-␥ (IFN-␥) assays are promising alternatives to the tuberculin skin test (TST), their serial testing performance is unknown. Objective: To compare TST and IFN-␥ conversions and reversions in healthcare workers. Methods: We prospectively followed-up 216 medical and nursing students in India who underwent baseline and repeat testing (after 18 mo) with TST and QuantiFERON-TB Gold In-Tube (QFT). TST conversions were defined as reactions greater than or equal to 10 mm, with increments of 6 or 10 mm over baseline. QFT conversions were defined as baseline IFN-␥ less than 0.35 and follow-up IFN-␥ greater than or equal to 0.35 or 0.70 IU/ml. QFT reversions were defined as baseline IFN-␥ greater than or equal to 0.35 and followup IFN-␥ less than 0.35 IU/ml. Results: Of the 216 participants, 48 (22%) were TST-positive, and 38 (18%) were QFT-positive at baseline. Among 147 participants with concordant baseline negative results, TST conversions occurred in 14 (9.5%; 95% confidence interval [CI] ϭ 5.3-15.5) using the 6 mm increment definition, and 6 (4.1%; 95% CI ϭ 1.5-8.7) using the 10 mm increment definition. QFT conversions occurred in 17/147 participants (11.6%; 95% CI ϭ 6.9-17.9) using the definition of IFN-␥ greater than or equal to 0.35 IU/ml, and 11/147 participants (7.5%; 95% CI ϭ 3.8-13.0) using IFN-␥ greater than or equal to 0.70 IU/ml. Agreement between TST (10 mm increment) and QFT conversions (у 0.70 IU/ml) was 96% ( ϭ 0.70). QFT reversions occurred in 2/28 participants (7%) with baseline concordant positive results, as compared with 7/10 participants (70%) with baseline discordant results (p Ͻ 0.001). Conclusions: IFN-␥ assay shows promise for serial testing, but repeat results need to be interpreted carefully. To meaningfully interpret serial results, the optimal thresholds to distinguish new infections from nonspecific variations must be determined.

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“…IGRAs are as sensitive and more specific than the tuberculin skin test for detecting latent tuberculosis infection (LTBI) (1,2) and have better correlation with gradient of M. tuberculosis exposure (3)(4)(5)(6)(7)(8). In 2005, the Centers for Disease Control and Prevention recommended that QuantiFERON TB-Gold (QFT-G; Cellestis, Carnegie, Australia), the first FDA-approved, commercially available IGRA to experience widespread use, could be used for targeted screening of LTBI in all circumstances in which the tuberculin skin test (TST) is used (9).…”

mentioning

confidence: 99%

Evaluation of Quantitative IFN-γ Response for Risk Stratification of Active Tuberculosis Suspects

Metcalfe¹,

Cattamanchi²,

Vittinghoff³

et al. 2010

Am J Respir Crit Care Med

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Rationale: The contribution of interferon-g release assays (IGRAs) to appropriate risk stratification of active tuberculosis suspects has not been studied. Objectives: To determine whether the addition of quantitative IGRA results to a prediction model incorporating clinical criteria improves risk stratification of smear-negative-tuberculosis suspects. 78; P , 0.001) and correctly reclassified 32% of tuberculosis suspects (95% CI,11-52%; P , 0.001) into higher-risk or lower-risk categories. However, quantitative IFN-g results did not significantly improve appropriate risk reclassification beyond that provided by clinician assessment of risk (4%; 95% CI, 27 to 122%; P 5 0.14). Conclusions: Higher quantitative IFN-g results were associated with active tuberculosis, and added clinical value to a prediction model incorporating conventional risk factors. Although this benefit may be attenuated within highly experienced centers, the predictive accuracy of quantitative IFN-g levels should be evaluated in other settings.

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Quantitative T Cell Assay Reflects Infectious Load of Mycobacterium tuberculosis in an Endemic Case Contact Model

Cited by 65 publications

References 14 publications

Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test

Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test

Serial Testing of Health Care Workers for Tuberculosis Using Interferon-γ Assay

Evaluation of Quantitative IFN-γ Response for Risk Stratification of Active Tuberculosis Suspects

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