Search Results (78)

Adolescents are underprioritized in tuberculosis (TB) control, and the effect of TB preventive therapy (TPT) in this group is unstudied in China. This study evaluated the protective effect of TPT in Chinese adolescents during TB outbreaks. Data on TB outbreaks and contact screening in six cities (2019–2021) were collected. Adolescents eligible for TPT were identified via tuberculin skin test or interferon-gamma assay and grouped by TPT. Follow-up until 31 December 2023, tracked TB onset. The protective effect was analyzed using KM survival curves and COX models. From January 2019 to December 2021, 136 school TB outbreaks were reported, involving 10,837 adolescent contacts. Among these, 624 adolescent contacts met the criteria for TPT (latent TB infection) at baseline; 277 (44.4%) initiated a 3-month isoniazid plus rifampicin preventive therapy (TPT group), while 347 (55.6%) did not receive TPT (non-TPT group). By 31 December 2023, 11 of these 624 adolescent contacts developed active TB, with 1 patient in the TPT group and 10 patients in the non-TPT group. The cumulative incidence of TB was 0.36% in the TPT group vs. 2.88% in the non-TPT group (χ² = 5.65, p = 0.017). This corresponds to an approximate 87% reduction in TB incidence among adolescent contacts who received TPT compared to those who did not. TPT reduced TB incidence by ~90% among adolescent contacts. Timely, comprehensive, and standardized TPT is recommended to minimize TB risks in educational settings and achieve a TB-free campus. Full article

Background: Identifying latent tuberculosis infection (LTBI) is critical for pediatric TB control in China, especially among students from high-burden areas. With no gold-standard test, we compared the tuberculin skin test (TST) and interferon-gamma release assay (IGRA), focusing on factors related to test discordance. Materials and Methods: TST was administered to 1047 local and 900 migrant students; all migrants also received IGRA. TST cutoffs of 5 mm and 10 mm were applied. Agreement was measured using Cohen’s Kappa, and determinants of discordance were analyzed with binary logistic regression. Results: Migrant students had higher TST positivity than locals (28.89% vs. 19.67%, p < 0.001). The agreement between IGRA and TST-12 mm (k = 0.491) was higher than that observed for TST-10 mm (k = 0.466) and TST-5 mm (k = 0.356). Subgroup analyses across sex, residence, ethnicity, BMI, TB contact, and BCG history confirmed superior consistency for TST-12 mm. Individuals without BCG vaccination were less likely to show discordance between IGRA and TST-12 mm (OR = 0.32, 95% CI: 0.10–0.81). Conclusions: Using a 12 mm cutoff improves TST accuracy for students from high-burden areas. IGRA should be preferred for individuals with BCG vaccination history. Full article

Background: Tuberculosis (TB) remains a major public health challenge among children and adolescents in high-burden countries. Xinjiang, the region with the highest TB incidence in China, has limited data on the clinical and epidemiological characteristics of pediatric TB. Methods: We conducted a retrospective cross-sectional study of children and adolescents (≤17 years) hospitalized with TB at a regional referral hospital in Xinjiang between 1 January 2020 and 31 December 2022. Demographic, clinical, and laboratory data were analyzed, and risk factors for extrapulmonary TB (EPTB) and severe TB were assessed. Results: A total of 253 patients were included, of whom 54.9% (139/253) had pulmonary TB (PTB) and 45.1% (114/253) had EPTB. EPTB was more common among children <5 years (78.9%, 15/19). The predominant clinical symptoms were fever (55.7%, 141/253), cough (66.8%, 169/253), fatigue (60.9%, 154/253), and night sweats (51.8%, 131/253). Tuberculous meningitis (TBM) was the most frequent EPTB manifestation (40.4%, 46/114). Younger age, rural residence, and absence of BCG vaccination were associated with a higher risk of EPTB. Laboratory findings showed high positivity rates for tuberculin skin test (96.1%, 99/103) and interferon-γ release assay (84.5%, 196/232), but low yields for smear microscopy and Xpert MTB/RIF, especially in EPTB cases. Conclusions: Pediatric TB in Xinjiang is characterized by a high burden of EPTB, particularly TBM in young children. Strengthening early diagnosis and improving access to effective diagnostic tools are essential to reduce morbidity and improve outcomes in this vulnerable population. Full article

Background: The world health goal of eliminating tuberculosis (TB) is heavily hinged on timely and efficient diagnosis and treatment. The interferon-γ release assays (I.G.R.A.s) can diagnose Mycobacterium tuberculosis infection and offer an alternative to the centuries-old tuberculin skin test (T.S.T.). Yet there is disagreement over replacing the T.S.T. with I.G.R.A.s as a standard tool. Objective: We aim to assess the diagnostic ability of I.G.R.A.s compared with T.S.T. for detecting active TB cases. Methods: A systematic review identified relevant studies from four databases. In the diagnostic meta-analysis conducted with OpenMeta Analyst software, we calculated the sensitivity (SN) and specificity (SP) for active TB detection via I.G.R.A. and T.S.T. methods compared to TB culture. Results included pooled estimates for SN and SP with 95% confidence intervals (CI), stratified by age, immunity, I.G.R.A. type, and T.S.T. cut-off. Results: Our meta-analysis revealed that TB diagnosis using T.S.T. showed an SN of 72.4% and SP of 79.3%, while I.G.R.A. demonstrated higher accuracy with an SN of 78.9% and SP of 85.7%. Subgroup analysis by age indicated that I.G.R.A. consistently outperformed T.S.T. in both adult and pediatric populations. Among immunocompromised individuals, T.S.T. had low SN (23%) but high SP (91.2%), whereas I.G.R.A. had higher SN (65.6%) but lower SP (81.9%). Immunocompetent subjects showed that T.S.T. had SN of 72% and SP of 87.3%, while I.G.R.A. had higher SN (82.9%) and SP (89.1%). Evaluation by I.G.R.A. type revealed that T-SPOT.GIT demonstrated a higher SN but lower SP compared to QFT-GIT. Assessing T.S.T. cut-offs, SP was highest (88.8%) at ≥15 mm, while SN peaked (71.6%) at ≥5 mm. Conclusions: I.G.R.A. consistently showed higher diagnostic accuracy than T.S.T. across most studied subgroups, indicating its potential superiority in active TB diagnosis. Full article

Identification of young children with Mycobacterium tuberculosis (Mtb) infection is critical to curb pediatric morbidity and mortality. The optimal test to identify young children with Mtb infection remains controversial. Using a tuberculosis (TB) household contact (HHC) study design among 130 Ugandan children less than 5 years of age with Mtb exposure, this study was conducted to determine the following: (1) the prevalence of Mtb immune sensitization in young children heavily exposed to TB using both the tuberculin skin test (TST) and QuantiFERON Gold Plus (QFT-Plus) interferon gamma release assay, and to examine the concordance of these two tests; and (2) the diagnostic accuracy of TST and QFT-plus for confirmed and unconfirmed TB in young children. Prevalence of Mtb immune sensitization was determined using TST at both 5 mm and 10 mm thresholds for positivity; manufacturer’s thresholds were utilized to establish QFT-Plus positivity. Concordance analysis between TST and QFT-Plus results was performed, including correlation between QFT-Plus tube TB.1 and tube TB.2. The sensitivity and specificity of TST and QFT-Plus for confirmed and unconfirmed TB was determined, and a logistic regression model was utilized to estimate the odds of TB. A 5 mm TST threshold identified the most children with Mtb sensitization (49.2%) and had moderate agreement with QFT-Plus (Cohen’s Kappa 0.59). The odds of TB were two times higher among children with a positive TST using a 5 mm threshold. Concordance between 10 mm TST threshold and QFT-Plus was substantial (Cohen’s Kappa 0.65), with higher concordance observed among older children (2–5 years). The QFT-Plus tube TB.1 and tube TB.2 results were highly correlated. Positive TST using a 5 mm threshold demonstrated the highest sensitivity for TB (60%), whereas QFT-Plus testing demonstrated the highest specificity (72%). Overall, our findings support that among a population of young, BCG-vaccinated children with heavy household exposure to TB, the TST using a 5 mm threshold identified more children with evidence of Mtb immune sensitization, and children with TB disease, than the QFT-Plus. These findings are highly relevant for children who are TB HHCs in endemic settings, and most at risk for TB following an exposure. We recommend that TST testing continue to be performed to assess for Mtb sensitization in young, TB-exposed children in TB-endemic settings to both prioritize provision of preventive therapy and to aide in diagnosis of pediatric TB. Full article

Background/Objectives: Healthcare workers (HCWs) are globally recognized as a high-risk group for tuberculosis (TB) infection. However, limited data exist on the prevalence of latent TB infection (LTBI) and associated occupational risk factors in the Mexican context. Identifying the burden of LTBI is essential for effective prevention. This study aimed to estimate the prevalence of LTBI among HCWs in a tertiary care hospital in Mexico and to explore associated risk factors. Methods: An analytical cross-sectional study was conducted among 300 HCWs (including physicians, nurses, and stretcher-bearers) at a tertiary-level hospital in Mexico. Sociodemographic and occupational data were collected through a structured questionnaire. LTBI screening was performed using the tuberculin skin test (TST), with positive results confirmed via the QuantiFERON-TB Gold assay. Associations between relevant variables and LTBI were assessed using logistic regression models, adjusted for potential confounders. Results: The prevalence of LTBI was 16.7%. After adjusting for confounders, male HCWs had significantly higher odds of LTBI compared to females (adjusted odds ratio [aOR] = 2.02; 95% confidence interval [CI]: 1.06–3.80). Although elevated odds of LTBI were also observed among physicians, stretcher-bearers, and those with direct contact with TB patients, these associations were not statistically significant. Conclusion: LTBI represents a relevant occupational health issue among HCWs, with nearly one in six workers affected. Early detection and prevention of TB in healthcare settings are critical to protecting individual workers and public health. These findings highlight the need to strengthen occupational TB surveillance and prevention strategies in similar healthcare environments. Full article

Background: Bovine tuberculosis (bTB) is an infectious disease which causes significant damage to the farming industry and remains a disease of global significance. Although control strategies have focused on a test and cull approach primarily based around specific cell-mediated immune responses, serological assays are increasingly being used as a supplementary test alongside skin testing and interferon-gamma release (IGRA) assays. The UK is moving towards the use of the Bacillus Calmette–Guérin (BCG) vaccination of cattle as an additional targeted control tool against bTB. However, there are concerns over its potential impact on the outcomes of bTB diagnostic tests and other non-TB assays, such as serological tests for Mycobacterium avium subsp. paratuberculosis (MAP). Methods: We investigated the performance of commercially available serology tests designed to detect bTB and MAP using serum samples from BCG-vaccinated animals which were subsequently infected with Mycobacterium bovis (M. bovis). Results: BCG vaccination per se did not significantly impact the specificity of serological diagnostic tests for bTB or Johne’s disease. However, increased numbers of false-positive responses in bTB serology tests were seen in BCG-vaccinated animals 3 weeks following a tuberculin skin test, where up to 23% and 54% of animals gave a positive result in IDEXX and Enferplex tests, respectively. Furthermore, M. bovis infection gave rise to false-positive test results for Johne’s disease, irrespective of the animals’ prior BCG vaccination status. Conclusions: Caution should be taken when assessing results from serology tests for bTB if tuberculin skin testing has occurred shortly before collection of blood from BCG-vaccinated cattle. Furthermore, these results highlight the potential for misdiagnosis of MAP infection when using serology tests in bTB-infected cattle. Full article

Bovine tuberculosis (bTB) is a zoonotic infectious disease and a chronic wasting illness. Accordingly, detecting and eradicating bTB remains a significant challenge in South Korea. This study evaluated the efficacy of a modified enzyme-linked immunosorbent assay (ELISA) protocol for detecting bTB in cattle. The protocol included two ELISA tests: one performed on the day of purified protein derivative (PPD) inoculation and another seven days post-inoculation. Results show a significant increase in ELISA detection rates, from 11% to 76%, particularly in cattle that tested positive for the tuberculin skin test (TST) and/or interferon-gamma (IFN-γ) assays (p < 0.0001). Notably, some cattle that were negative or had doubtful results in TST and IFN-γ assays transitioned to ELISA positive post-PPD inoculation. Additionally, some cattle identified as positive only by ELISA (S/p value ≥ 0.3) were confirmed to have bTB through gross examination or real-time reverse transcription polymerase chain reaction (rRT-PCR). The proposed protocol was validated in bTB outbreak farms using S/p thresholds of 0.3 (PPD inoculation day) and 0.5 (seven days post-PPD), enabling the detection of infected cattle missed by TST and IFN-γ assays. Implementing this approach successfully eradicated bTB in outbreak farms with minimal culling. These findings highlight the potential of incorporating sequential ELISA tests to enhance bTB detection and support eradication efforts. Full article

Background: Exposure time to a tuberculosis (TB) index case may be a marker of a recent latent tuberculosis infection (LTBI) risk. The aim of this study was to determine the LTBI risk involved in immigrant contact based on exposure time to pulmonary TB index cases. Methods: We conducted a 30-month LTBI prevalence study of pulmonary TB immigrant contacts in Catalonia (1 January 2019–30 June 2021). Contacts with LTBI were identified by means of the tuberculin skin test and/or interferon gamma release assay. Variables associated with LTBI in contacts were analysed using adjusted OR (aOR) and 95% confidence interval (CI) values. Results: LTBI prevalence was 37.4% (939/2509). Prevalence was higher in men than women (40.6% versus 33.5%; p < 0.001), and in all age groups, relative to children <5 years (12.2%; p < 0.001)). Prevalence increased with exposure time to the index case; relative to <6 h/week exposure, LTBI risk was greater for both ≥6 h/day (aOR = 2.0; 95% CI: 1.5–2.6) and <6 h/day but ≥6 h/week (aOR = 1.6; 95% CI: 1.1–2.2). Conclusions: The LTBI risk in immigrant contacts increases with recent exposure time to the index case, and may suggest recent LTBI in immigrants. Full article

Background/Objectives: Patients with rheumatic immune-mediated diseases (rheumatic-IMID) and latent tuberculosis (LTBI) are at an increased risk of developing active tuberculosis (TB); therefore, screening is recommended before starting biological treatment. The aims of this study were as follows: (i) to assess the prevalence of LTBI, (ii) to determine the importance of using a booster test in TST-negative patients, (iii) to compare the tuberculin skin test (TST) with the interferon-gamma release assay (IGRA), (iv) to perform a review of the prevalence of LTBI. Methods: A cross-sectional hospital study was performed, including patients diagnosed with rheumatic-IMID who underwent a TST and/or IGRA during the period 2016–2020. If the first TST was negative, a new TST (booster) was performed. Results: A total of 1117 patients were included. The overall prevalence of LTBI was estimated to be 31.7% (95% confidence interval, 29.74–33.66). The LTBI prevalence ranged from 38.5% for vasculitis to 14% for sarcoidosis. The booster test was positive in 22.9% of 817 patients with a negative or indeterminate IGRA. The IGRA was positive in 3.8% of 793 patients with a negative booster.The adjusted Cohen’s kappa coefficient between TST (+booster) and IGRA was 0.62. Conclusions: LTBI is frequent in patients with rheumatic-IMID. IGRA and TST (+booster) show a moderate, fair grade of agreement. Therefore, performing both tests before biological therapy should be highly recommended. Full article

Human T-cell leukemia virus type 1 (HTLV-1) is associated with an increased risk of tuberculosis (TB). This study aimed to evaluate the performance of the QuantiFERON-TB Gold (QFT) test for the diagnosis of Mycobacterium tuberculosis (MTB) infection in HTLV-1-infected individuals. HTLV-1-infected participants were divided into four groups: HTLV-1-infected individuals with a history of tuberculosis (HTLV/TB), individuals with positive HTLV and tuberculin skin tests (HTLV/TST+) or negative TST (HTLV/TST−), and HTLV-1-negative individuals with positive TST results (HN/TST+). We compared the diagnostic performance of the QFT assay with that of the TST as a reference and evaluated test sensitivity, specificity, accuracy, likelihood ratio, and diagnostic odds ratio. The results showed a higher frequency of positive TST results and induration diameter ≥10 mm in HTLV-1-infected individuals than in the controls. The QFT test was more frequently positive in the HTLV/TB group than in the other groups, while a combined analysis of HTLV/TB and HTLV/TST+ indicated a QFT sensitivity of 57.5%. No significant differences were found in the other diagnostic performance measures, as QFT test results were in agreement with TST results, particularly in TST-negative individuals. Given the low sensitivity of QFT for LTBI in individuals infected with HTLV-1, the TST may be preferable in regions where both infections are endemic. Full article

Interferon-gamma release assays (IGRAs) have gained attention for the diagnosis of latent tuberculosis infection (LTBI) due to their higher specificity compared to the tuberculin skin test (TST). However, the IGRA’s performance varies across different populations. This study evaluated the diagnostic performance of three IGRAs (TBF-FIA, TBF-ELISA, and QFT-Plus) in Ghana, comparing them among individuals exposed and unexposed to MTB infection. Conducted in TB clinics across three regions, this prospective and cross-sectional study included healthy individuals with no known TB exposure (unexposed group) and patients with confirmed active TB (exposed group). Blood samples were tested using all three assays as per the manufacturers’ guidelines. The TBF-ELISA showed 3.4% higher sensitivity but 4.6% lower specificity compared to QFT-Plus. The TBF-FIA had sensitivity of 78.5–87.3% and specificity of 82.9–90.0%. These findings indicate that while the three IGRAs offer similar diagnostic accuracy, the variations in specificity and limited data on assays like TBF-FIA require further investigation. Full article

Bovine tuberculosis is caused by Mycobacterium bovis, a member of the M. tuberculosis complex of mycobacterial species that cause tuberculosis in humans and animals. Diagnosis of bovine tuberculosis has relied on examinations of cell-mediated immune responses to M. bovis proteins using tuberculin skin testing and/or interferon gamma release assays. Even when using these methods, disease detection during the earliest phases of infection has been difficult, allowing a window for cattle-to-cattle transmission to occur within a herd. Alternative means of diagnosis could include methods to detect M. bovis or M. bovis DNA in bodily fluids such as nasal secretions, saliva, or blood. During the first 8 weeks after experimental aerosol infection of 18 calves, M. bovis DNA was detected in nasal swabs from a small number of calves 5, 6, and 8 weeks after infection and in samples of saliva at 1, 7, and 8 weeks after infection. However, at no time could culturable M. bovis be recovered from nasal swabs or saliva. M. bovis DNA was not found in blood samples collected weekly and examined by real-time PCR. Interferon gamma release assays demonstrated successful infection of all calves, while examination of humoral responses using a commercial ELISA identified a low number of infected animals at weeks 4–8 after infection. Examination of disease severity through gross lesion scoring did not correlate with shedding in nasal secretions or saliva, and calves with positive antibody ELISA results did not have more severe disease than other calves. Full article

Bovine tuberculosis (bTB) continues to have significant economic and veterinary health impacts on cattle herds where the disease remains endemic. The continual tailoring of policies to address such maintenance requires an in-depth analysis of national data, underpinning new control strategies. In Ireland, when outbreaks occur, ancillary testing of herd mates deemed to be at the highest risk of exposure to reactors is undertaken using the interferon gamma (GIF) test. This highest risk cohort was hypothesised to be of a higher future risk despite this ancillary testing. We used a dataset from Ireland to model bovine test failure to the comparative tuberculin skin test using a survival analysis (observations: 39,248). Our primary exposure of interest was whether an animal that tested negative had a GIF test after the disclosure of infection within a herd during a bTB breakdown. There was evidence that animals with a negative GIF test during a breakdown had an increased risk of failing a test relative to other animals from the same herds without this exposure. The time to failure was 48.8% (95%CI: 38.3–57.5%) shorter for the exposed group relative to the unexposed group during a two-year follow-up period (2019–2022; time ratio: 0.51; 95%CI: 0.43–0.62; p < 0.001). The results from this study suggest that animals who were GIF-tested, having been deemed to have a higher risk of exposure, subsequently had shorter time-to-test failure periods. The absolute numbers of failure are small (only 2.5% of animals go on to fail during 2-year follow-up). Importantly, however, a high proportion of these high-risk herds included in the dataset failed at least one test at the follow-up (21/54 herds), impacting breakdown duration or recurrence. Such risk-informed targeting of animals could be utilised in future control policies, though further research is warranted. Full article

Latent tuberculosis infection (LTBI) is common in people living with HIV (PLHIV) in high-TB-burden settings. Active TB is associated with specific stool taxa; however, little is known about the stool microbiota and LTBI in PLHIV. We characterised the stool microbiota of PLHIV with [interferon-γ release assay (IGRA)- and tuberculin skin test (TST)-positive] or without (IGRA- and TST-negative) LTBI (n = 25 per group). The 16S rRNA DNA sequences were analysed using QIIME2, Dirichlet-Multinomial Mixtures, DESeq2, and PICRUSt2. No α- or β-diversity differences occurred by LTBI status; however, LTBI-positive people were Faecalibacterium-, Blautia-, Gemmiger-, and Bacteroides-enriched and Moryella-, Atopobium-, Corynebacterium-, and Streptococcus-depleted. Inferred metagenome data showed that LTBI-negative-enriched pathways included several metabolite degradation pathways. Stool from LTBI-positive people demonstrated differential taxa abundance based on a quantitative response to antigen stimulation. In LTBI-positive people, older people had different β-diversities than younger people, whereas in LTBI-negative people, no differences occurred across age groups. Amongst female PLHIV, those with LTBI were, vs. those without LTBI, Faecalibacterium-, Blautia-, Gemmiger-, and Bacteriodes-enriched, which are producers of short-chain fatty acids. Taxonomic differences amongst people with LTBI occurred according to quantitative response to antigen stimulation and age. These data enhance our understanding of the microbiome’s potential role in LTBI. Full article