Dataset Information

Cough Aerosol Cultures of Mycobacterium tuberculosis: Insights on TST / IGRA Discordance and Transmission Dynamics.

ABSTRACT:

Rationale

The diagnosis of latent tuberculosis (TB) infection (LTBI) is complicated by the absence of a gold standard. Discordance between tuberculin skin tests (TST) and interferon gamma release assays (IGRA) occurs in 10-20% of individuals, but the underlying mechanisms are poorly understood.

Methods

We analyzed data from a prospective household contact study that included cough aerosol culture results from index cases, environmental and contact factors. We assessed contacts for LTBI using TST and IGRA at baseline and six weeks. We examined TST/IGRA discordance in qualitative and quantitative analyses, and used multivariable logistic regression analysis with generalized estimating equations to analyze predictors of discordance.

Measurements and results

We included 96 TB patients and 384 contacts. Discordance decreased from 15% at baseline to 8% by six weeks. In adjusted analyses, discordance was related to less crowding (p = 0.004), non-cavitary disease (OR 1.41, 95% CI: 1.02-1.96; p = 0.03), and marginally with BCG vaccination in contacts (OR 1.40, 95% CI: 0.99-1.98, p = 0.06).

Conclusions

We observed significant individual variability and temporal dynamism in TST and IGRA results in household contacts of pulmonary TB cases. Discordance was associated with a less intense infectious exposure, and marginally associated with a BCG-mediated delay in IGRA conversion. Cough aerosols provide an additional dimension to the assessment of infectiousness and risk of infection in contacts.

SUBMITTER: Jones-Lopez EC

PROVIDER: S-EPMC4578948 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and show no evidence of immune sensitization to Mycobacterium tuberculosis (Mtb) as defined by persistently negative tuberculin skin tests (TST) and interferon gamma release assays (IGRA). This group has been identified and defined as HIV+ persistently TB, tuberculin and IGRA negative (HITTIN). To investigate potential innate mechanisms unique to individuals with the HITTIN phenotype we compared their neutrophil Mtb infection response to that of PLWH, with no TB history, but who test persistently IGRA positive, and tuberculin positive (HIT). Neutrophil samples from 17 HITTIN (PMNHITTIN) and 11 HIT (PMNHIT) were isolated and infected with Mtb H37Rv for 1h and 6h. RNA was extracted and used for RNAseq analysis. Since there was no significant differential transcriptional response at 1h between infected PMNHITTIN and PMNHIT, we focused on the 6h timepoint. When compared to uninfected PMN, PMNHITTIN displayed 3106 significantly upregulated and 3548 significantly downregulated differentially expressed genes (DEGs) (absolute cutoff of a log2FC of 0.2, FDR < 0.05) whereas PMNHIT demonstrated 3816 significantly upregulated and 3794 significantly downregulated DEGs following 6h Mtb infection. Contrasting the log2FC 6h infection response to Mtb from PMNHITTIN against PMNHIT, 2285 genes showed significant differential response between the two groups. Overall PMNHITTIN had a lower fold change response to Mtb infection compared to PMNHIT. According to pathway enrichment, Apoptosis and NETosis were differentially regulated between HITTIN and HIT PMN responses after 6h Mtb infection. To corroborate the blunted NETosis transcriptional response measured among HITTIN, fluorescence microscopy revealed relatively lower neutrophil extracellular trap formation and cell loss in PMNHITTIN compared to PMNHIT, showing that PMNHITTIN have a distinct response to Mtb.

Project description:This study aims to compare the latent tuberculosis infection (LTBI) screening strategy of interferon-gamma release assay (IGRA)-alone and in combination with tuberculin skin tests (TSTs) before the initiation of tumor necrosis factor (TNF) inhibitor treatment in patients with inflammatory arthritis. Between January 2011 and June 2017, we enrolled 476 patients who were followed up for ?1 year after the TNF inhibitor initiation in a tertiary referral center in South Korea. Inflammatory arthritis comprised rheumatoid arthritis in 266 (55.9%) and ankylosing spondylitis in 210 (44.1%) patients. The following strategies were used for LTBI screening during the study period: (i) from January 2011 to October 2014, the combination of TST and QuantiFERON-TB Gold In-Tube (QFT-GIT); (ii) between November 2014 and February 2015, QFT-GIT-alone and (iii) since March 2015, either the combination of TST and QFT-GIT or QFT-GIT-alone depending on the attending physician's choice. We compared the screening strategies of QFT-GIT alone and in combination with TST. Overall, 338 (71.0%) patients received LTBI screening tests using the combination of TST and QFT-GIT, and 138 (29.0%) received QFT-GIT-alone. In addition, the LTBI tests were positive in 159 (47.0%) of 338 patients using the combination tests, and 43.8% (148/338) required LTBI treatment. Meanwhile, the LTBI tests were positive in 32.6% (45/138) of QFT-GIT-alone patients, and 30.4% (42/138) required LTBI treatment. Among 338 patients who received combination tests, 2 patients developed active tuberculosis within 1 year after the TNF inhibitor initiation. Of patients who received QFT-GIT-alone, no patient developed tuberculosis. In conclusion, among patients who received QFT-GIT-alone, the number of patients who required LTBI treatment declined compared to the TST and QFT-GIT combination, and none developed active tuberculosis within 1 year, suggesting that QFT-GIT-alone could be a potential screening strategy for diagnosing LTBI in patients with inflammatory arthritis in South Korea.