Despite current guidelines for tuberculosis (TB) control in health care settings, which focused on smear-positive cases, prevention of nosocomial TB transmission continues to be a challenge. Here, we ...report the results of the first hospital-wide prospective study applying interferon-gamma release assay to investigate the role of smear-negative, culture-positive index cases in nosocomial TB transmission.
We prospectively identified cases of culture-confirmed smear-negative pulmonary TB receiving aerosol-generating procedures (AGPs) and cases of culture-confirmed smear-positive pulmonary TB admitted at a medical center. Nosocomial transmission was evaluated by screening their close contacts for latent TB infection (LTBI) using an interferon-gamma release assay.
A total of 93 smear-negative index receiving AGP and 122 smear-positive index were enrolled. Among them, 13 (14.0%) and 43 (35.2%) index cases, respectively, had secondary cases of LTBI (P < .001). Sputum smear negativity (adjusted odds ratio: 0.20 0.08-0.48) and AGP (sputum suction; adjusted odds ratio: 3.48 1.34-9.05) are independent factors of transmission. A similar proportion in the close contacts of the 2 index groups had LTBI (17 15.3% and 63 16.0%, respectively), and the former index group contributed to 21.3% of the nosocomial transmission.
Smear-negative, culture-positive index cases receiving AGPs could be as infectious as smear-positive index cases. Hospital TB control policy should also focus on the former group.
•The role of smear-negative index cases in nosocomial transmission remains unknown.•Smear-negative cases receiving AGPs could be as infectious as smear-positive cases.•Smear-negative cases may be responsible for 21.3% nosocomial TB transmissions.•Ongoing physician education to optimize the utilization of TB-NAAT is imperative.•Hospital TB control should also focus on smear-negative index receiving AGPs.
Disease modifying therapies compromise immune response to SARS-Cov2 or its vaccine in patients with immune system diseases (ISD). Therefore, analysis of the humoral and cellular responses against ...Spike is of utmost importance to manage ISD patients. A single-center retrospective study was conducted to evaluate the impact of COVID-19 immunization in 87 ISD patients and 81 healthy controls. We performed a whole blood interferon gamma release assay using SARS-Cov2 Spike and Nucleocapsid recombinant proteins in order to evaluate T-cell memory response, and an IgG anti-Spike ELISA to evaluate humoral response. Cellular (26.4%) and humoral (44.8%) responses were negative against Spike in ISD patients following COVID-19 immunization. In univariate analysis, an anti-Spike T cell defective response was associated with the use of glucocorticoids (Odds ratio OR = 10.0; p < 10−4), serum albumin level ≤40 g/L (OR = 18.9; p < 10−4), age over 55 years old (OR = 3.9, p = 0.009) and ≤2 vaccine injections (OR = 4.9; p = 0.001). The impact of glucocorticoids persisted after adjustment for age and number of vaccine injections (OR = 8.38, p < 0.001). In contrast, the humoral response was impacted by the use of anti-CD20 mAb (OR = 24.8, p < 10−4), and an extended time since immunization (≥75 days; OR = 4.3, p = 0.002). Double defective cellular/humoral responses (6.9%) were typically encountered in glucocorticoids and/or anti-CD20 mAb treated ISD with a serum albumin level ≤40 g/L (OR = 17.5; p = 0.002). Glucocorticoid usage, B cell depleting therapies, and a low serum albumin level were the main factors associated with a non-response to COVID-19 immunization in ISD patients. These results need further confirmation in larger studies.
•Anti-Spike cellular and humoral responses are altered in immune system diseases.•Anti-Spike cellular response is affected by long-term glucocorticoid usage.•Anti-Spike humoral response is impaired by B-cell depleting and glucocorticoid therapies.•Serum albumin level, time from immunization, and >55 years old constitute additional risks for defective immune responses.
BACKGROUND: South Texas has higher TB disease incidence than much of the United States. We evaluated a multi-site South Texas interferon-gamma release assay (IGRA)-based testing and latent TB ...infection (LTBI) treatment program targeting high-risk populations.METHODS:
Number of IGRA tests, test results, LTBI confirmation, and treatment outcomes were collected over 2.5 years. Sixteen semi-structured patient interviews and 10 site-based focus groups were conducted with providers, nurses, and administrators. Grounded theory identified themes associated with
successful outcomes.RESULTS: Of 9,050 IGRA tests, 687 (8%) were positive; 340 (49%) confirmed as LTBI; 191 initiated LTBI treatment; and 130 (68% of initiators) completed treatment. Patient barriers to treatment completion included lack of knowledge, misconceptions, and treatment
toxicities. Clinic staff concurred that toxicity was a barrier to treatment and requiring new processes with limited resources were implementation barriers.CONCLUSIONS: Over 9,000 patients were screened with a high prevalence of IGRA positivity, but confirming LTBI, initiating,
and completing treatment were challenging. Qualitative evaluation supports low literacy patient education on LTBI and toxicities and expanded support for process implementation and provider training. These findings highlight challenges at all levels of the LTBI care cascade and provide patient,
staff, and provider perspectives on implementation of these programs.
High rates of tuberculosis (TB) transmission occur in hospitals in high-incidence countries, yet there is no validated way to evaluate the impact of hospital design and function on airborne infection ...risk. We hypothesized that personal ambient carbon dioxide (CO2) monitoring could serve as a surrogate measure of rebreathed air exposure associated with TB infection risk in health workers (HWs).
We analyzed baseline and repeat (12-month) interferon-γ release assay (IGRA) results in 138 HWs in Cape Town, South Africa. A random subset of HWs with a baseline negative QuantiFERON Plus (QFT-Plus) underwent personal ambient CO2 monitoring.
Annual incidence of TB infection (IGRA conversion) was high (34%). Junior doctors were less likely to have a positive baseline IGRA than other HWs (OR, 0.26; P = .005) but had similar IGRA conversion risk. IGRA converters experienced higher median CO2 levels compared to IGRA nonconverters using quantitative QFT-Plus thresholds of ≥0.35 IU/mL (P < .02) or ≥1 IU/mL (P < .01). Median CO2 levels were predictive of IGRA conversion (odds ratio OR, 2.04; P = .04, ≥1 IU/mL threshold). Ordinal logistic regression demonstrated that the odds of a higher repeat quantitative IGRA result increased by almost 2-fold (OR, 1.81; P = .01) per 100 ppm unit increase in median CO2 levels, suggesting a dose-dependent response.
HWs face high occupational TB risk. Increasing median CO2 levels (indicative of poor ventilation and/or high occupancy) were associated with higher likelihood of HW TB infection. Personal ambient CO2 monitoring may help target interventions to decrease TB transmission in healthcare facilities and help HWs self-monitor occupational risk, with implications for other airborne infections including coronavirus disease 2019.
Intestinal tuberculosis still has a high incidence, especially in developing countries. The biggest challenge of this disease is the establishment of the diagnosis because the clinical features are ...not typical. Investigations such as culture, acid-fast bacilli (AFB) staining, and histopathology have low sensitivity, so other investigations are needed. Latest molecular-based diagnostic modalities such as GeneXpert, interferon-gamma (IFN-γ) release assays (IGRA), polymerase chain reaction (PCR), multiplex-PCR, and immunological markers are expected to help diagnose intestinal tuberculosis. This article review will examine the latest diagnostic modalities that can be used as a tool in establishing the diagnosis of intestinal tuberculosis.
Through a literature search, we were able to review the diagnostic values of various available diagnostic modalities as the appropriate additional test in intestinal tuberculosis. Culture as a gold standard has a sensitivity and specificity value of 9.3% and 100% with the MGIT BACTEC system as the most recommended medium. The sensitivity values of AFB staining, histopathology examination, GeneXpert, IGRA, PCR, multiplex-PCR and, immunological markers were ranged between 17.3 and 31%; 68%; 81-95.7%; 74-88%; 21.6-65%; 75.7-93.1%; and 52-87%, respectively. Meanwhile the specificity values were 100%; 77.1%; 91-100%; 74-87%; 93-100%; 96.4-100%; and 70-95%, respectively.
The combination of clinical examination, conventional examination, and the latest molecular-based examination is the best choice for establishing the diagnosis of intestinal tuberculosis. Most recent modalities such as multiplex PCR and immunological marker examinations are diagnostic tools that deserve to be used in diagnosing intestinal tuberculosis as their sensitivity and specificity values are quite high and more evidences are expected to support the application of these examinations shortly soon.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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El diagnóstico de la infección tuberculosa latente (ITL) mediante IGRA sigue generando debate. La experiencia empleando dos pruebas IGRA de manera simultánea es escasa. El objetivo de ...este estudio es comparar los resultados de dos versiones de QuantiFERON-TB Gold (In-Tube/Plus) con los de T-SPOT.TB y analizar la eficacia de esta estrategia dual (T-SPOT.TB + QTF) para el diagnóstico de la ITL en población con alguna condición inmunosupresora.
Estudio prospectivo (mayo 2015-junio 2017) que incluye 2.999 pacientes inmunodeprimidos y/o candidatos a terapias biológicas, a los que se les realizó de manera simultánea dos IGRA: grupo-1 (1.535 pacientes): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); grupo-2 (1.464 pacientes): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus).
La concordancia entre QTF-GIT y T-SPOT.TB fue del 83,19% (κ = 0,532). Las proporciones de resultados positivos, negativos e indeterminados fueron, respectivamente: 14,33 vs. 17,06%; 82,41 vs. 74,46%; y 3,25 vs. 8,46%. La concordancia entre QTF-Plus y T-SPOT.TB fue del 87,56% (κ=0,609). Las proporciones de resultados positivos, negativos e indeterminados fueron, respectivamente: 15,02 vs. 15,36%; 82,92 vs. 79,37%; y 2,04 vs. 5,25%. Las discordancias entre T-SPOT.TB y QTF-Plus fueron del 12,43%, que implicaban que había 103 pacientes positivos y otros 79 pacientes negativos a expensas exclusivamente de uno de los dos IGRA.
Se evidenció una mayor concordancia entre QTF-Plus y T-SPOT.TB que entre QTF-GIT y T-SPOT.TB. Sin embargo, creemos que la proporción de resultados discordantes entre T-SPOT.TB y QTF-Plus es lo suficientemente relevante clínicamente como para justificar el empleo simultáneo de dos IGRA en este grupo específico de pacientes.
The diagnosis of latent tuberculous infection (LTI) by IGRA continues to generate debate. Experience in the simultaneous use of 2 IGRA tests is scant. The aim of this study was to compare the results of 2 versions of QuantiFERON-TB Gold (In-Tube/Plus) with those of T-SPOT.TB, and to analyse the effectiveness of a dual strategy (T-SPOT.TB + QTF) for the diagnosis of LTI in an immunosuppressed population.
We conducted a prospective study (May 2015-June 2017) that included 2,999 immunosuppressed patients and/or candidates for biologics, in whom 2 simultaneous IGRA tests were performed: Group 1 (1535 patients): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); Group 2 (1464 patients): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus).
The concordance between QTF-GIT and T-SPOT.TB was 83.19% (κ=0.532). The percentage of positive, negative, and indeterminate results were, respectively: 14.33% vs. 17.06%; 82.41% vs. 74.46%; and 3.25% vs. 8.46%. The concordance between QTF-Plus and T-SPOT.TB was 87.56% (κ=0.609). The percentage of positive, negative, and indeterminate results were, respectively: 15.02% vs. 15.36%; 82.92% vs. 79.37%; and 2.04% vs. 5.25%. Discrepancies between T-SPOT.TB and QTF-Plus were 12.43%, suggesting that 103 patients were positive and another 79 were negative due exclusively to 1 of the 2 IGRAs.
Greater concordance was found between QTF-Plus and T-SPOT.TB than between QTF-GIT and T-SPOT.TB. However, we believe that the proportion of discrepancies between T-SPOT.TB and QTF-Plus is sufficiently important from a clinical point of view to justify the simultaneous use of 2 IGRA in this specific patient group.
Interferon-gamma release assays (IGRAs) are approved for children ≥2 years old to aid in diagnosis of Mycobacterium tuberculosis (TB) infection and disease. Tuberculin skin tests (TSTs) continue to ...be the recommended method for diagnosis of TB infection in children <2 years, in part due to limited data and concern for high rates of uninterpretable results.
We performed a retrospective cohort study of IGRA use in patients <2 years old in 2 large Boston healthcare systems. The primary outcome was the proportion of valid versus invalid/indeterminate IGRA results. Secondary outcomes included concordance of IGRAs with paired TSTs and trends in IGRA usage over time.
A total of 321 IGRA results were analyzed; 308 tests (96%) were valid and 13 (4%) were invalid/indeterminate. Thirty-seven IGRAs were obtained in immunocompromised patients; the proportion of invalid/indeterminate results was significantly higher among immunocompromised (27%) compared with immunocompetent (1%) patients ( P < 0.001). Paired IGRAs and TSTs had a concordance rate of 64%, with most discordant results in bacille Calmette-Guérin-vaccinated patients. The proportion of total TB tests that were IGRAs increased over the study period (Pearson correlation coefficient 0.85, P < 0.001).
The high proportion of valid IGRA test results in patients <2 years of age in a low TB prevalence setting in combination with the known logistical and interpretation challenges associated with TSTs support the adoption of IGRAs for this age group in certain clinical scenarios. Interpretation of IGRAs, particularly in immunocompromised patients, should involve consideration of the broader clinical context.
In individuals living with HIV infection the development of tuberculosis (TB) is associated with rapid progression from asymptomatic TB infection to active TB disease. Sputum-based diagnostic tests ...for TB have low sensitivity in minimal and subclinical TB precluding early diagnosis. The immune response to novel
expressed and latency associated antigens may help to measure the early stages of infection and disease progression and thereby improve early diagnosis of active TB disease.
Serial prospectively sampled cryopreserved lymphocytes from patients of the Swiss HIV Cohort Study developing TB disease ("cases") and matched patients with no TB disease ("controls") were stimulated with 10 novel
antigens. Cytokine concentrations were measured in cases and controls at four time points prior to diagnosis of TB: T1-T4 with T4 being the closest time point to diagnosis.
50 samples from nine cases and nine controls were included. Median CD4 cell count at T4 was 289/ul for the TB-group and 456/ul for the control group. Viral loads were suppressed in both groups. At T4 Rv2431c-induced and Rv3614/15c-induced interferon gamma-induced protein (IP)-10 responses and Rv2031c-induced and Rv2346/Rv2347c-induced tumor necrosis factor (TNF)-α responses were significantly higher in cases compared to controls (
< 0.004). At T3 - being up to 2 years prior to TB diagnosis - Rv2031c-induced TNF-α was significantly higher in cases compared to controls (
< 0.004). Area under the receiver operating characteristics (AUROC) curves resulted in an AUC > 0.92 for all four antigen-cytokine pairs.
The
-specific immune response in HIV-infected individuals that progress toward developing TB disease is different from those in HIV-infected individuals that do not progress to developing TB. These differences precede the clinical diagnosis of active TB up to 2 years, paving the way for the development of immune based diagnostics to predict TB disease at an early stage.
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