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Diabetes mellitus and latent tuberculosis infection: an updated meta-analysis and systematic review.BMC Infectious Diseases Nov 2023Previous studies have demonstrated an association between diabetes mellitus (DM) and latent tuberculosis infection (LTBI). This study was conducted to update the current... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have demonstrated an association between diabetes mellitus (DM) and latent tuberculosis infection (LTBI). This study was conducted to update the current understanding of the association between DM and LTBI. By conducting a systematic review and meta-analysis using adjusted odds ratios (aOR) or risk ratios (aRR), we aimed to further explore the association between DM and LTBI and provide essential reference for future research.
METHODS
We conducted comprehensive searches in Embase, Cochrane Library, and PubMed without imposing any start date or language restrictions, up to July 19, 2022. Our study selection encompassed observational research that compared from LTBI positive rates in both DM and non-DM groups and reported aRR or aOR results. The quality of the included studies was assessed utilizing the Newcastle-Ottawa Scale. Pooled effect estimates were calculated using random-effects models, along with their associated 95% confidence intervals (CI).
RESULTS
We included 22 studies involving 68,256 subjects. Three cohort studies were eligible, with a pooled aRR of 1.26 (95% CI: 0.71-2.23). Nineteen cross-sectional studies were eligible, with a pooled aOR of 1.21 (95% CI: 1.14-1.29). The crude RR (cRR) pooled estimate for three cohort studies was 1.62 (95% CI: 1.03-2.57). Among the cross-sectional studies we included, sixteen studies provided crude ORs, and the crude OR (cOR) pooled estimate was 1.64 (95% CI: 1.36-1.97). In the diagnosis of diabetes, the pooled aOR of the HbA1c group was higher than that of self-reported group (pooled aOR: 1.56, 95% CI: 1.24-1.96 vs. 1.17, 95% CI: 1.06-1.28).
CONCLUSION
Our systematic review and meta-analysis suggest a positive association between DM and LTBI. Individuals with DM may have a higher risk of LTBI compared to those without DM. These findings provide important insights for future research and public health interventions in managing LTBI in diabetic populations.
Topics: Humans; Latent Tuberculosis; Cross-Sectional Studies; Diabetes Mellitus; Tuberculin Test; Cohort Studies; Risk Factors; Observational Studies as Topic
PubMed: 37940866
DOI: 10.1186/s12879-023-08775-y -
Public Health Action Sep 2023TB infection (TBI) is diagnosed using the technique-dependent tuberculin skin test (TST) or costly, more accurate interferon-gamma release assays. The TST (⩾10 mm)...
SETTING
TB infection (TBI) is diagnosed using the technique-dependent tuberculin skin test (TST) or costly, more accurate interferon-gamma release assays. The TST (⩾10 mm) threshold was indicated by previous research among household contacts in Vietnam, but routine implementation with a different tuberculin reagent showed unexpectedly low TST positivity.
OBJECTIVE
TST (⩾5 mm and ⩾10 mm) results were compared to QuantiFERON™-TB Gold Plus (QFT) results in household contacts during community campaigns in 2020 and 2021.
DESIGN
This was a cross-sectional multi-center implementation study.
RESULTS
Among 1,330 household contacts in 2020, we found a TBI prevalence of 38.6% (QFT), similar to TST ⩾5 mm (37.4%) and higher than TST ⩾10 mm (13.1%). QFT+/TST+ was higher for TST ⩾5 mm (20.7%) than TST ⩾10 mm (9.4%). QFT was not discordant with TST ⩾5 mm (McNemar's test = 0.6, = 0.5) but was discordant with TST ⩾10 mm (McNemar's test = 263.9, < 0.01). Older age and Southern region increased odds for positive TST ⩾5 mm and QFT with weaker associations for TST ⩾10 mm. Agreement and discordance were similar in 2021 for 1,158 household contacts.
CONCLUSION
Tuberculin reagents affect TST positivity rates. High TB burden countries should monitor reliability of TBI diagnosis, including tuberculin potency, cold chain, and TST technique to optimize eligibility for TB preventive treatment.
PubMed: 37736581
DOI: 10.5588/pha.23.0020 -
Clinical Infectious Diseases : An... Aug 2023Transcriptomic profiling of adults with tuberculosis (TB) has become increasingly common, predominantly for diagnostic and risk prediction purposes. However, few studies...
BACKGROUND
Transcriptomic profiling of adults with tuberculosis (TB) has become increasingly common, predominantly for diagnostic and risk prediction purposes. However, few studies have evaluated signatures in children, particularly in identifying those at risk for developing TB disease. We investigated the relationship between gene expression obtained from umbilical cord blood and both tuberculin skin test conversion and incident TB disease through the first 5 years of life.
METHODS
We conducted a nested case-control study in the Drakenstein Child Health Study, a longitudinal, population-based birth cohort in South Africa. We applied transcriptome-wide screens to umbilical cord blood samples from neonates born to a subset of selected mothers (N = 131). Signatures identifying tuberculin conversion and risk of subsequent TB disease were identified from genome-wide analysis of RNA expression.
RESULTS
Gene expression signatures revealed clear differences predictive of tuberculin conversion (n = 26) and TB disease (n = 10); 114 genes were associated with tuberculin conversion and 30 genes were associated with the progression to TB disease among children with early infection. Coexpression network analysis revealed 6 modules associated with risk of TB infection or disease, including a module associated with neutrophil activation in immune response (P < .0001) and defense response to bacterium (P < .0001).
CONCLUSIONS
These findings suggest multiple detectable differences in gene expression at birth that were associated with risk of TB infection or disease throughout early childhood. Such measures may provide novel insights into TB pathogenesis and susceptibility.
Topics: Child, Preschool; Humans; Infant; Infant, Newborn; Birth Cohort; Case-Control Studies; Fetal Blood; Latent Tuberculosis; South Africa; Transcriptome; Tuberculin; Tuberculin Test; Tuberculosis; Female
PubMed: 37144357
DOI: 10.1093/cid/ciad268 -
PloS One 2024No gold standard diagnostic test exists for latent tuberculosis infection (LTBI). The intra-dermal tuberculin skin test (TST) has known limitations and Interferon-gamma...
Tuberculin skin test and Interferon-gamma release assay agreement, and associated factors with latent tuberculosis infection, in medical and nursing students in Bandung, Indonesia.
BACKGROUND
No gold standard diagnostic test exists for latent tuberculosis infection (LTBI). The intra-dermal tuberculin skin test (TST) has known limitations and Interferon-gamma release assays (IGRA) have been developed as an alternative. We aimed to assess agreement between IGRA and TST, and risk factors for test positivity, in Indonesian healthcare students.
METHODS
Medical and nursing students starting their clinical training were screened using IGRA and TST. Agreement between the two tests was measured using Cohen's Kappa coefficient. Logistic regression was used to identify factors associated with test positivity.
RESULTS
Of 266 students, 43 (16.2%) were IGRA positive and 85 (31.9%) TST positive. Agreement between the two tests was 74.7% (kappa 0.33, 95% CI 0.21-0.45, P<0.0001). Students who had direct contact with family or friends with TB were less likely to be test positive using IGRA (AOR 0.18, 95% CI 0.05-0.64) and using TST (AOR 0.51, 95% CI 0.26-0.99).
CONCLUSION
Test positivity for LTBI was lower when measured by IGRA than by TST, with poor agreement between the two tests. Known close TB contact was unexpectedly negatively associated with positivity by either test. Longitudinal studies may be required to help determine the best test for LTBI in healthcare students in Indonesia.
Topics: Humans; Interferon-gamma Release Tests; Tuberculin Test; Indonesia; Latent Tuberculosis; Students, Nursing
PubMed: 38498488
DOI: 10.1371/journal.pone.0299874 -
Frontiers in Immunology 2023Bovine tuberculosis (bTB), caused by infection with , continues to cause significant issues for the global agriculture industry as well as for human health. An...
Bovine tuberculosis (bTB), caused by infection with , continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoonotic disease. In this study, high-throughput bulk RNA sequencing (RNA-seq) was used to characterise differential gene expression in γδ T cells - a subgroup of T cells that bridge innate and adaptive immunity and have known anti-mycobacterial response mechanisms. γδ T cell subsets are classified based on expression of a pathogen-recognition receptor known as (WC1) and we hypothesised that bTB disease may alter the phenotype and function of specific γδ T cell subsets. Peripheral blood was collected from naturally -infected (positive for single intradermal comparative tuberculin test (SICTT) and IFN-γ ELISA) and age- and sex-matched, non-infected control Holstein-Friesian cattle. γδ T subsets were isolated using fluorescence activated cell sorting ( = 10-12 per group) and high-quality RNA extracted from each purified lymphocyte subset (WC1.1, WC1.2, WC1 and γδ) was used to generate transcriptomes using bulk RNA-seq ( = 6 per group, representing a total of 48 RNA-seq libraries). Relatively low numbers of differentially expressed genes (DEGs) were observed between most cell subsets; however, 189 genes were significantly differentially expressed in the -infected compared to the control groups for the WC1.1 γδ T cell compartment (absolute log FC ≥ 1.5 and FDR ≤ 0.1). The majority of these DEGs (168) were significantly increased in expression in cells from the bTB+ cattle and included genes encoding transcription factors ( and ), chemokine receptors ( and ), granzymes (, and ) and multiple killer cell immunoglobulin-like receptor (KIR) proteins indicating cytotoxic functions. Biological pathway overrepresentation analysis revealed enrichment of genes with multiple immune functions including cell activation, proliferation, chemotaxis, and cytotoxicity of lymphocytes. In conclusion, γδ T cells have important inflammatory and regulatory functions in cattle, and we provide evidence for preferential differential activation of the WC1.1 specific subset in cattle naturally infected with .
Topics: Animals; Cattle; Humans; Mycobacterium bovis; T-Lymphocyte Subsets; Receptors, Antigen, T-Cell, gamma-delta; Tuberculosis, Bovine; Gene Expression
PubMed: 37942326
DOI: 10.3389/fimmu.2023.1265038 -
The International Journal of... Oct 2023Tajikistan has a high burden of rifampicin-resistant TB (RR-TB), with 2,700 new cases estimated for 2021 (28/100,000 population). TB is spread among household members...
Tajikistan has a high burden of rifampicin-resistant TB (RR-TB), with 2,700 new cases estimated for 2021 (28/100,000 population). TB is spread among household members through close interaction and children exposed through household contact progress to disease rapidly and frequently. We retrospectively analysed programmatic data from household contact tracing in Dushanbe over 50 months. We calculated person-years of follow-up, contact tracing yield, number needed to screen (NNS) and number needed to test (NNT) to find one new case, and time to diagnosis. We screened 6,654 household contacts of 830 RR-TB index cases; 47 new RR-TB cases were detected, 43 in Year 1 and 4 in Years 2 or 3. Ten were aged <5 years; 46/47 had TB symptoms, 34/45 had chest radiographs consistent with TB, 11/35 were Xpert Ultra-positive, 29/32 were tuberculin skin test-positive and 28/47 had positive TB culture and phenotypic drug susceptibility results. The NNS to find one RR-TB case was 141.57 and the NNT was 34.49. The yields for different types of contacts were as follows: 0.7% for screened contacts, 2.9% for tested contacts, 17.0% for symptomatic contacts and 12.1% for symptomatic contacts aged below 5 years. RR-TB household contact tracing was feasible and productive in Tajikistan, a low middle-income country with an inefficient healthcare delivery system.
Topics: Child; Humans; Tajikistan; Contact Tracing; Retrospective Studies; Tuberculosis; Rifampin; Tuberculosis, Multidrug-Resistant
PubMed: 37749832
DOI: 10.5588/ijtld.23.0066 -
Diagnostics (Basel, Switzerland) Jul 2023Hemodialysis (HD) patients should be screened for latent tuberculosis (TB) infection. We aimed to determine the frequency of latent TB infection in HD patients and to...
Hemodialysis (HD) patients should be screened for latent tuberculosis (TB) infection. We aimed to determine the frequency of latent TB infection in HD patients and to compare the effectiveness of the tests used. The files of 56 HD patients followed between 1 January 2021 and 1 October 2022 were retrospectively analyzed. Demographic data, the presence of the Bacillus Calmette-Guerin (BCG) vaccine, whether or not the patients had previously received treatment for TB before, the status of encountering a patient with active TB of patients over 18 years of age, without active tuberculosis and who had a T-SPOT.TB test or a Tuberculin Skin Test (TST) were obtained from the patient files. The presence of previous TB in a posterior-anterior (PA) chest X-ray was obtained by evaluating PA chest X-rays taken routinely. Of the patients, 60.7% ( = 34) were male and their mean age was 60.18 ± 14.85 years. The mean duration of dialysis was 6.43 ± 6.03 years, and 76.8% ( = 43) had 2 BCG scars. The T-SPOT.TB test was positive in 32.1% ( = 18). Only 20 patients (35.7%) had a TST and all had negative results. While the mean age of those with positive T-SPOT.TB results was higher ( = 0.003), the time taken to enter HD was shorter ( = 0.029). T-SPOT.TB test positivity was higher in the group that had encountered active TB patients ( = 0.033). However, no significant difference was found between T-SPOT.TB results according to BCG vaccine, albumin, urea and lymphocyte levels. Although T-SPOT.TB test positivity was higher in patients with a previous TB finding in a PA chest X-ray, there was no statistically significant difference ( = 0.093). The applicability of the TST in the diagnosis of latent TB infection in HD patients is difficult and it is likely to give false-negative results. The T-SPOT.TB test is not affected by the BCG vaccine and immunosuppression. Therefore, using the T-SPOT.TB test would be a more appropriate and practical approach in the diagnosis of latent TB in HD patients.
PubMed: 37510113
DOI: 10.3390/diagnostics13142369 -
Clinical Infectious Diseases : An... Jun 2023Subclinical tuberculosis has been increasingly recognized as a separate state in the spectrum of the disease. However, evidence on the transmissibility of subclinical...
BACKGROUND
Subclinical tuberculosis has been increasingly recognized as a separate state in the spectrum of the disease. However, evidence on the transmissibility of subclinical tuberculosis is still inconclusive.
METHODS
We re-analyzed the data from the 2007 combined tuberculosis prevalence and tuberculin surveys in Vietnam. Poisson regression with robust standard errors was conducted to assess the effect of clinical presentation of individuals with tuberculosis in the household on tuberculin skin test (TST) positivity among children aged 6-14 years who participated in the tuberculin survey, adjusting for child's age, smear status of the index patient, and other covariates.
RESULTS
In the multivariate analysis, we found significantly increased risks for TST positivity in children living with patients with clinical, smear-positive tuberculosis, compared with those living with individuals without tuberculosis (adjusted risk ratio [aRR]: 3.04; 95% confidence interval [CI]: 2.00-4.63) and with those living with patients with subclinical tuberculosis, adjusting for index smear status (aRR: 2.26; 95% CI: 1.03-4.96). Among children aged 6-10 years, those living with patients with clinical, smear-positive tuberculosis and those living with patients with subclinical, smear-positive tuberculosis had similarly increased risks of TST positivity compared with those living with individuals without tuberculosis (aRRs [95% CI] of 3.56 [1.91-6.62] and 3.11 [1.44-6.72], respectively).
CONCLUSIONS
Our findings support the hypothesis that smear-positive subclinical tuberculosis contributes to Mycobacterium tuberculosis transmission. To eliminate tuberculosis in 2035, control strategies need to address subclinical presentations of the disease.
Topics: Child; Humans; Tuberculosis, Pulmonary; Tuberculin; Risk Factors; Tuberculin Test; Tuberculosis; Mycobacterium tuberculosis; Surveys and Questionnaires
PubMed: 36660850
DOI: 10.1093/cid/ciad027 -
Revista Da Associacao Medica Brasileira... 2024Patients with rheumatic diseases have an increased risk of infections, especially tuberculosis. In this study, we aimed to recognize the positivity rate of tuberculosis...
OBJECTIVE
Patients with rheumatic diseases have an increased risk of infections, especially tuberculosis. In this study, we aimed to recognize the positivity rate of tuberculosis skin test in patients with rheumatoid arthritis and spondyloarthritis and the characteristics of the patients with positive results.
METHODS
Retrospective study of tuberculosis skin test results in patients followed from 2004 to 2021 in a single rheumatology unit. Data related to clinical and epidemiological features, along with treatment information referring to the period in which the tuberculosis skin test was performed, were collected from patients' charts.
RESULTS
A total of 723 tests were identified (448 tests in 269 rheumatoid arthritis patients and 275 in 174 spondyloarthritis patients). In the rheumatoid arthritis sample, 31/275 (11.5%) individuals had positive tests, and in the spondyloarthritis, 38/174 (21.8%) had positive tests. In the rheumatoid arthritis sample, patients with positive tuberculosis skin tests used a higher dose of methotrexate than those with negative results (median of 25 mg/week versus median of 20 mg/week respectively; p=0.02). In the spondyloarthritis sample, tuberculosis skin test positivity was associated with alcohol ingestion (13.1% versus 2.9% in users and non-users respectively; p=0.02) and sulfasalazine use (15.7% of positivity in users versus 5% in non-users; p=0.01).
CONCLUSION
The tuberculosis skin test-positive prevalence in rheumatoid arthritis was lower than in the spondyloarthritis sample. Patients with rheumatoid arthritis using a higher dosage of methotrexate or with spondyloarthritis using sulfasalazine had more frequency of tuberculosis skin test positivity and should be carefully followed by the attending physician in order to avoid the appearance of full-blown tuberculosis.
Topics: Humans; Methotrexate; Sulfasalazine; Tuberculin Test; Brazil; Prevalence; Retrospective Studies; Arthritis, Rheumatoid; Spondylarthritis; Tuberculosis
PubMed: 38265349
DOI: 10.1590/1806-9282.20230725 -
Journal of Microbiology, Immunology,... Oct 2023To assess associations between disease severity in index TB patients and QuantiFERON-TB Gold Plus (QFT-Plus) results in contacts, and predictors for QFT-Plus conversion...
OBJECTIVES
To assess associations between disease severity in index TB patients and QuantiFERON-TB Gold Plus (QFT-Plus) results in contacts, and predictors for QFT-Plus conversion in contacts over 6-12 months.
METHODS
TB patients (n = 295) and the contacts (n = 1051) were enrolled during 2018-2021 with QFT-Plus performed at baseline and months 6 and 12. A strong CD8 response was defined as TB2 interferon gamma (IFN-γ) response minus TB1 >0.6 IU/ml and stringent conversion as change from QFT-plus negative to high-positive QFT-Plus (TB1 or TB2 IFN-γ responses >0.7 IU/ml).
RESULTS
Contacts with index TB patients with sputum smear >1+ was associated with positive QFT-Plus compared to those without (p < 0.001). Contacts with index TB patients with bilateral lung disease were more likely to have strong CD8 responses than those without (p = 0.038). QFT-Plus stringent conversion occurred in 9.7% of contacts over 6-12 months. A TB1 IFN-γ response ≥0.03 IU/ml combined with a TB2 ≥0.06 IU/ml was predictive of a 19-fold increased risk for QFT-Plus stringent conversion in contacts (odd ratio 19.565 [8.484-45.116], p < 0.001).
CONCLUSION
Bacterial burden and bilateral lung disease of index TB patients were associated with positive QFT-Plus and strong CD8 responses in contacts. TB1 and TB2 IFN-γ responses were synergistically predictive of stringent conversion in contacts.
Topics: Humans; Latent Tuberculosis; Interferon-gamma Release Tests; Tuberculosis; Interferon-gamma; Lung Diseases; Mycobacterium tuberculosis; Tuberculin Test
PubMed: 37580184
DOI: 10.1016/j.jmii.2023.07.014