Dataset Information

Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil.

ABSTRACT: Interferon-gamma (IFN-?) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-? release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vitória, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8-12 weeks following enrollment and the test results were positive in 82% of TST+, 48% of TSTc, and 12% of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion.

SUBMITTER: Ribeiro-Rodrigues R

PROVIDER: S-EPMC4018294 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil.

Ribeiro-Rodrigues Rodrigo R Kim Soyeon S Coelho da Silva Flávia Dias FD Uzelac Aleksandra A Collins Lauren L Palaci Moíses M Alland David D Dietze Reynaldo R Ellner Jerrold J JJ Jones-López Edward E Salgame Padmini P

PloS one 20140512 5

Interferon-gamma (IFN-γ) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-γ release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PT ...[more]

PMID: 24819060

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Project description:BackgroundWorld Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.Materials and methodsA prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ?0.35 IU/ml and a positive TST as an induration of ?5 mm. A secondary outcome of TST induration ?10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.ResultsOf 1048 HHCs enrolled, 869 [median (IQR) age: 27 years (15-40)] had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% [95% CI (51, 57)], by TST was 55% [95% CI (52, 58)], by either test was 74% [95% CI (71, 77) and by both tests was 35% [95% CI (31, 38)]. Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.ConclusionPrevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.

Project description:BackgroundA high prevalence (50-80%) of Tuberculin Skin Test Positivity (TST+ >or=10 mm indurations) has been reported in TB endemic countries. This pool forms a huge reservoir for new incident TB cases. However, immune biomarkers associated with TST conversion are largely unknown. The objective of this study was to identify immune biomarkers associated with TST conversion after acute Mycobacterium tuberculosis (MTB) exposure.Methodology/principal findingsA 24 month longitudinal study was carried out in a recently MTB exposed cohort of household contacts (HC = 93; 75% TST+). Control group consisted of unexposed community controls (EC = 59; 46%TST+). Cytokine secretion was assessed in whole blood cultures in response to either mycobacterial culture filtrate (CF) antigens or mitogens (PHA or LPS) using Elisa methodology. Compared to the EC group, the HC group at recruitment (Kruskal-Wallis Test) showed significantly suppressed IFN gamma (p = 0.0001), raised IL-10 (p = 0.0005) and raised TNF alpha (p = 0.001) in response to CF irrespective of their TST status. Seventeen TST-HC, showed TST conversion when retested at 6 months. Post TST conversion (paired t tests) significant increases were observed for CF induced IFN gamma (p = 0.038), IL-10 (p = 0.001) and IL-6 (p = 0.006). Cytokine responses were also compared in the exposed HC group with either recent infection [(TST converters (N = 17)] or previous infection [TST+ HC (N = 54)] at 0, 6, 12 and 24 months using ANOVA on repeated measures. Significant differences between the exposed HC groups were noted only at 6 months. CF induced IFN gamma was higher in previously infected HC group (p = 0.038) while IL-10 was higher in recently infected HC group (p = 0.041). Mitogen induced cytokine secretion showed similar differences for different group.Conclusions/significanceOur results suggest that TST conversion is associated with early increases in IFN gamma and IL-10 responses and precedes latency by several months post exposure.

Project description:Background: Andes orthohantavirus (ANDV) is the sole etiologic agent of Hantavirus Cardiopulmonary Syndrome in Chile and, until now, the only Hantavirus known to be transmitted by person-to-person route. The main risk of person-to-person transmission is to be a sexual partner of an index case, and deep kissing the main mechanism of infection. Experimental reports suggest that ANDV infection can be inhibited by some saliva components. Therefore, some host factors like saliva quality, could help to explain why some individuals do not become infected even though their exposure to the virus is high. Aim: To compare some saliva components, such cytokines and mucins, between ANDV-infected cases (exposed-sick), their close household contacts (exposed-not sick) and healthy control not exposed. Methods: Sixty-nine confirmed ANDV-infected cases, 76 close household contacts exposed to ANDV but not infected (CHC) and 39 healthy control not exposed (HCNE). The following components were measured in saliva: secretory immunoglobulin A (sIgA) by ELISA; cytokines (IL1β, IL12p70, TNFα, INFy, IL10, IL6, VEGF, IP10, and IL8) by Multiplex Assay and mucins MUC7 and MUC5B by Western Blotting. Results: Among infected cases, CHC and HCNE analyzed 74, 45, and 33% were men, respectively (p ≤ 0.05). The average age for cases, CHC and HCNE was 37.7, 28.7, and 32 years, respectively (p ≤ 0.05). The average concentration of sIgA in infected cases was 4.846 mg/mL, higher than for CHC group, 0.333 mg/mL (p ≤ 0.05). For cytokines, significant differences were found comparing all groups for IFNy, IL12p70, and IL8. Among CHC group, there was a higher frequency of detection of MUC7 isoform (62.6%; 31/49) compared to ANDV-infected cases (40.5%; 17/42) (p < 0.05). Similarly, presence of MUC5B was higher among CHC groups (62.16%; 46/74) than in ANDV-infected cases (44.4%; 28/63) (p < 0.05). Conclusions: Three salivary components showed differences between infected cases and close household contacts (sIgA, cytokines, and mucins). These differences can be explained by the acute state of the disease in the ANDV-infected cases group. However, the differences in MUC5B and isoforms of MUC7 are not entirely explainable by the infection itself. This work represents a novel description of salivary components in the context of ANDV infection.

Dataset Information

Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil.

Publications

Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil.

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