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1.
BMC Infect Dis ; 24(1): 984, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39285314

ABSTRACT

BACKGROUND: The latent tuberculosis infection (LTBI) burden is still unclear in schoolchildren and adolescents in China. Previous study and daily surveillance data indicate a LTBI detection gap. The research objective was to evaluate the LTBI burden and detection gap among schoolchildren and adolescents in China. METHODS: A cross-sectional study was conducted among 69,667 schoolchildren and adolescents in Chongqing, China between September 2022 and December 2023 implemented by Chongqing Municipal Institute of Tuberculosis using tuberculin skin test (TST) and creation tuberculin skin test (C-TST). To evaluate the LTBI detection gap, the pulmonary tuberculosis (PTB) screening data implemented by Chongqing Municipal Institute of Tuberculosis have been compared with the data in 2021 implemented by community-level medical and health care institutions. RESULTS: The LTBI prevalence rate using TST and C-TST implemented by Chongqing Municipal Institute of Tuberculosis was 12.8% (95%CI, 12.5-13%) and 6.4% (95%CI, 6-6.8%) respectively. The LTBI prevalence rate by Chongqing Municipal Institute of Tuberculosis was 9.6% higher than that by community-level medical and health care institutions (χ2 = 2931.9, P < 0.001). CONCLUSIONS: The LTBI detection gap existed among schoolchildren and adolescents in Chongqing, and it also may exist in other similar countries and regions. National screening strategy needs improvement. Regular training and quality assurance could improve the performance of TST and C-TST and close the detection gap of LTBI.


Subject(s)
Latent Tuberculosis , Mass Screening , Tuberculin Test , Humans , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Cross-Sectional Studies , China/epidemiology , Adolescent , Child , Male , Female , Prevalence , Mass Screening/methods , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/diagnosis
2.
BMC Infect Dis ; 24(1): 1005, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39300351

ABSTRACT

BACKGROUND: Tuberculosis (TB) is one of the most widespread infectious diseases worldwide, typically persisting in the body as a latent TB infection (LTBI). Patients with type 2 diabetes have an increased risk of LTBI progressing to active TB. Therefore, this study determined the prevalence and predictors of LTBI and assessed the agreement between tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in diagnosing LTBI among type 2 diabetics in Sana'a city, Yemen. METHODS: A cross-sectional study was conducted among 150 type 2 diabetics in private health facilities in Sana'a in 2023. Data about demographics, diabetes-related characteristics, and potential risk factors for LTBI were collected using a structured questionnaire. Patients were then screened for LTBI using TST and IGRA. Univariate analysis was used to identify LTBI-associated risk factors, and multivariable binary logistic regression was used to identify independent predictors of LTBI. The agreement between TST and IGRA for diagnosing LTBI was assessed using Cohen's kappa coefficient (κ). RESULTS: LTBI was prevalent among 29.3% of type 2 diabetics using both types of tests (25.3% with IGRA and 21.3% with TST). Male gender was an independent predictor of LTBI (AOR = 4.4, 95% confidence interval: 1.30-15.08; P = 0.018). However, being employed (AOR = 0.3, 95% CI: 0.09-0.75; P = 0.013) and longer duration since diabetes diagnosis (AOR = 0.3, 95% CI: 0.12-0.98; P = 0.046) were identified as predictors of lower LTBI risk. The agreement between TST and IGRA for the diagnosis of LTBI was 88%, with a good and statistically significant agreement between the two test types (κ = 0.670; P < 0.001). CONCLUSIONS: LTBI is common among type 2 diabetics seeking medical care in Sana'a city, with about one-third of them possibly being latently infected. A higher LTBI risk can be predicted among males, while a lower risk can be predicted among those employed or being diagnosed with diabetes for at least five years. The TST shows good agreement with IGRA in diagnosing LTBI among type 2 diabetics, supporting its continued use as a cost-effective and easily accessible test for diagnosing LTBI in the country.


Subject(s)
Diabetes Mellitus, Type 2 , Interferon-gamma Release Tests , Latent Tuberculosis , Tuberculin Test , Humans , Diabetes Mellitus, Type 2/complications , Male , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Latent Tuberculosis/complications , Female , Yemen/epidemiology , Cross-Sectional Studies , Middle Aged , Interferon-gamma Release Tests/methods , Adult , Prevalence , Risk Factors , Aged
3.
Adv Rheumatol ; 64(1): 70, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39272122

ABSTRACT

OBJECTIVES: To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. METHODS: Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). RESULTS: A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6-12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6-10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5-13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 - 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. CONCLUSION: These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.


Subject(s)
Arthritis, Psoriatic , Arthritis, Rheumatoid , Latent Tuberculosis , Spondylitis, Ankylosing , Tuberculin Test , Tumor Necrosis Factor-alpha , Humans , Retrospective Studies , Arthritis, Rheumatoid/drug therapy , Male , Female , Arthritis, Psoriatic/drug therapy , Middle Aged , Spondylitis, Ankylosing/drug therapy , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effects , Aged , Cohort Studies , Endemic Diseases , Tumor Necrosis Factor Inhibitors/therapeutic use
4.
Indian J Tuberc ; 71(4): 465-470, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39278681

ABSTRACT

BACKGROUND AND AIM: Cutaneous Tuberculosis constitutes 1-1.5 % of extrapulmonary tuberculosis with a wide clinical spectrum which relies upon the portal of entry of mycobacteria and patient's immunity. Complications of cutaneous tuberculosis if treatment is delayed includes hazardous sequel like dissemination and disfigurement. Early diagnosis and cure is the ultimate way to prevent such complications. This has motivated us to study clinicoepidemiological, histopathological profile and outcome post treatment of cutaneous tuberculosis patients of our region in detail. METHODS: Total 78 patients were studied during the period of August 2018-2022, who were suspicious to have cutaneous tuberculosis clinically of which 54 were confirmed with histopathology. Patient related clinicoepidemiological data such as age, gender, past history of tuberculosis or contact history, chest-x ray, tuberculin test positivity was analysed in a retrospective manner. RESULTS: Among the 54 biopsy proven cases (33 women, 21 men) ranging from 6 to 76 years, 27 patients have been found to have Lupus Vulgaris followed by 15 cases of scrofuloderma. Acid fast bacilli were seen in 9 patients with majority in scrofuloderma. Histopathology revealed epithelioid cell granuloma without necrosis in 34 cases and caseation necrosis in 20 patients. 48 patients showed complete recovery with 6 months of Anti-Koch Treatment and some complications were observed in remaining. Limitation of this research was that long term follow up was not possible. CONCLUSION: Lack of familiarity might lead to overlooking of a standard presentation or misdiagnosis. So, an eagle eye with high degree of suspicion is crucial for control and prevention of morbidity and for improving socio-economic burden of cutaneous tuberculosis.


Subject(s)
Tertiary Care Centers , Tuberculosis, Cutaneous , Humans , Male , Female , India/epidemiology , Tuberculosis, Cutaneous/epidemiology , Tuberculosis, Cutaneous/diagnosis , Tuberculosis, Cutaneous/pathology , Adult , Middle Aged , Adolescent , Young Adult , Aged , Retrospective Studies , Child , Antitubercular Agents/therapeutic use , Lupus Vulgaris/epidemiology , Lupus Vulgaris/pathology , Lupus Vulgaris/diagnosis , Lupus Vulgaris/drug therapy , Tuberculin Test
5.
mSystems ; 9(9): e0062824, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39162406

ABSTRACT

Mycobacterium tuberculosis (Mtb) exposure leads to a range of outcomes including clearance, latent TB infection (LTBI), and pulmonary tuberculosis (TB). Some heavily exposed individuals resist tuberculin skin test (TST) and interferon-gamma (IFNγ) release assay (IGRA) conversion (RSTR), which suggests that they employ IFNγ-independent mechanisms of Mtb control. Here, we compare monocyte epigenetic profiles of RSTR and LTBI from a Ugandan household contact cohort. Chromatin accessibility did not differ between uninfected RSTR and LTBI monocytes. By contrast, methylation significantly differed at 174 CpG sites and across 63 genomic regions. Consistent with previous transcriptional findings in this cohort, differential methylation was enriched in lipid- and cholesterol-associated pathways including the genes APOC3, KCNQ1, and PLA2G3. In addition, methylation was enriched in Hippo signaling, which is associated with cholesterol homeostasis and includes CIT and SHANK2. Lipid export and Hippo signaling pathways were also associated with gene expression in response to Mtb in RSTR as well as IFN stimulation in monocyte-derived macrophages (MDMs) from an independent healthy donor cohort. Moreover, serum-derived high-density lipoprotein from RSTR had elevated ABCA1-mediated cholesterol efflux capacity (CEC) compared to LTBI. Our findings suggest that resistance to TST/IGRA conversion is linked to regulation of lipid accumulation in monocytes, which could facilitate early Mtb clearance among RSTR subjects through IFNγ-independent mechanisms.IMPORTANCETuberculosis (TB) remains an enduring global health challenge with millions of deaths and new cases each year. Despite recent advances in TB treatment, we lack an effective vaccine or a durable cure. While heavy exposure to Mycobacterium tuberculosis often results in latent TB latent infection (LTBI), subpopulations exist that are either resistant to infection or contain Mtb with interferon-gamma (IFNγ)-independent mechanisms not indicative of LTBI. These resisters provide an opportunity to investigate the mechanisms of TB disease and discover novel therapeutic targets. Here, we compare monocyte epigenetic profiles of RSTR and LTBI from a Ugandan household contact cohort. We identify methylation signatures in host lipid and cholesterol pathways with potential relevance to early TB clearance before the sustained IFN responses indicative of LTBI. This adds to a growing body of literature linking TB disease outcomes to host lipids.


Subject(s)
Epigenesis, Genetic , Latent Tuberculosis , Lipid Metabolism , Mycobacterium tuberculosis , Humans , Lipid Metabolism/genetics , Latent Tuberculosis/immunology , Latent Tuberculosis/microbiology , Latent Tuberculosis/genetics , Latent Tuberculosis/metabolism , Male , Adult , Female , Tuberculin Test , Interferon-gamma Release Tests , Monocytes/metabolism , Monocytes/immunology , DNA Methylation , Uganda/epidemiology , Cohort Studies
6.
PLoS One ; 19(8): e0293272, 2024.
Article in English | MEDLINE | ID: mdl-39190640

ABSTRACT

BACKGROUND: A novel skin test-called Diaskintest (DT)-containing specific M. tuberculosis antigens is in clinical use in the Russian Federation (RF). This test may improve diagnosis of tuberculosis (TB) infection. The use and performance of the DT was described and compared to the tuberculin skin test (TST). METHODS: Data on children <18 years referred to a TB reference centre (Jan/2018- Dec/2019) with ≥1 DT and TST result available were analysed. An immune correlate of TB infection was defined as a positive TST (≥10 mm induration) or a positive DT (any induration). RESULTS: Of 2710 included cases, the median age was 9.0 (IQR 5.7-13.1) years and 97.5% were BCG immunised. Overall, 1976 (79.9%) were TB uninfected, 724 (26.7%) had an immune correlate of TB infection and 10 (0.4%) TB disease. Reasons for referral were: positive or increasing skin test results in routine screening (992, 36.6%), screening before admission to a health care institution (501, 18.5%) and TB contact (457, 16.9%). DT was positive in 11.7% (308/2625) and TST in 63.1% (467/740) (Kappa 0.08, 95% CI:0.013-0.14). A positive DT was associated with older age (OR 1.16 (95% CI: 1.13-1.19) per year). Among TB contacts DT positivity was associated with contagiousness: highest proportion of positivity of 12.0% was observed when the index case was smear positive. CONCLUSION: In a setting with universal BCG vaccination and regular screening with TST, DT was used to rule out TB infection as TST was commonly positive. We found an association of DT positivity and contagiousness of the index case in children contacts. These observations may suggest improved specificity and sensitivity of DT compared to TST.


Subject(s)
Tuberculin Test , Tuberculosis , Humans , Child , Tuberculin Test/methods , Male , Female , Child, Preschool , Adolescent , Tuberculosis/diagnosis , Mycobacterium tuberculosis/immunology , Skin Tests/methods , BCG Vaccine/immunology , Infant , Antigens, Bacterial/immunology , Antigens, Bacterial/analysis
7.
Int J Tuberc Lung Dis ; 28(9): 412-418, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39188004

ABSTRACT

OBJECTIVETo summarise the available literature regarding clinical presentation, immunological and microbiological diagnosis, treatment, and outcomes of miliary TB in children and adolescents.METHODSFour databases were searched from 1 January 1950 to 31 January 2023. "Miliary" and "disseminated" TB were the main search concepts.FINDINGSOf 257 studies, 1,883 patients with miliary TB were included. Bacille Calmette-Guérin (BCG) vaccination was confirmed in 223/549 (40.6%) children. Central nervous system (CNS) involvement was reported in 367/924 (39.7%) cases; many of them had no neurological symptoms despite also having abnormal brain imaging. Of 1,112 children with known outcomes, 341 (30.6%) died; mortality was higher in publications before 1995 (41.5%) and in children with CNS involvement (31.9%). TB microbiological confirmation (55.8%) and sensitivity of tuberculin skin test (46.9%) and QuantiFERON Gold (72.4%) were overall low.CONCLUSIONSEvidence is lacking to support best practices for paediatric miliary TB. Whether lumbar puncture (LP) and brain imaging should both be routinely done in miliary TB children, or a step-by-step approach based on initial LP findings, remains unclear. This study should inform policymakers and funding agencies about current significant gaps that need to be addressed by future high-quality studies..


Subject(s)
Tuberculosis, Miliary , Adolescent , Child , Child, Preschool , Humans , Tuberculin Test , Tuberculosis, Miliary/diagnosis , Tuberculosis, Miliary/mortality
8.
WHO South East Asia J Public Health ; 13(1): 9-15, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-39167130

ABSTRACT

INTRODUCTION: Management of latent tuberculosis infection (LTBI) was introduced as a national policy in Sri Lanka in 2022, targeting high-risk groups, including health-care workers (HCWs). This study aimed to identify the potential risk factors for LTBI among HCWs in government hospitals. METHODS: A case-control study was conducted. Cases and controls were identified by a screening survey conducted among those tested by the tuberculin skin test (TST). The survey was conducted among HCWs of eight government hospitals in Colombo in 2022. LTBI cases were defined as TST positives (≥10 mm) without a history of pulmonary tuberculosis (TB) and controls were those rated as negative. The cases-to-control ratio was 1:1, with a sample size of 128 cases and 128 controls. Multiple logistic regression analysis was conducted to identify the risk factors. RESULTS: The significant risk factors identified included age ≥40 years (adjusted odds ratio [AOR] - 2.4, 95% confidence interval [CI]: 1.28-4.47) having a service duration of ≥6 years (AOR - 2.92, CI: 1.469-5.82), not maintaining distance (AOR - 2.83, CI: 1.43-5.58) and not wearing face masks when dealing with suspected or diagnosed TB patients (AOR - 3.55, CI: 1.80-7.00), and settings with inadequate TB infection control practices (AOR - 3.47, CI: 1.85-6.47). CONCLUSION: Improving infection control measures, training HCWs on TB prevention, providing adequate personal protective equipment, and initiating screening for LTBI among HCWs are recommended.


Subject(s)
Health Personnel , Latent Tuberculosis , Humans , Sri Lanka/epidemiology , Risk Factors , Male , Female , Case-Control Studies , Adult , Latent Tuberculosis/epidemiology , Latent Tuberculosis/diagnosis , Health Personnel/statistics & numerical data , Middle Aged , Tuberculin Test , Young Adult
10.
BMC Genomics ; 25(1): 762, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39107682

ABSTRACT

Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), represents a significant problem for the agriculture industry as well as posing a risk for human health. Current diagnostic tests for bTB target the cell-mediated immune (CMI) response to infection with M. bovis, primarily through screening of animals with the tuberculin skin test. Epigenetic modifications have been shown to alter the course of the immune response and differentially methylated regions (DMRs) might also influence the outcome of the skin test in cattle. Whole Genome Bisulphite Sequencing (WGBS) was used to profile DNA methylation levels from peripheral blood of a group of cattle identified as test positive for M. bovis (positive for the single intradermal comparative tuberculin test (SICTT) and/or the interferon-γ release assay compared to a test negative control group [n = 8/group, total of 16 WGBS libraries]. Although global methylation profiles were similar for both groups across the genome, 223 DMRs and 159 Differentially Promoter Methylated Genes (DPMGs) were identified between groups with an excess of hypermethylated sites in SICTT positive cattle (threshold > 15% differential methylation). Genes located within these DMRs included the Interleukin 1 receptor (IL1R1) and MHC related genes (BOLA and BOLA-DQB). KEGG pathway analysis identified enrichment of genes involved in Calcium and MAPK signalling, as well as metabolism pathways. Analysis of DMRs in a subset of SICTT negative cattle that were IFN-γ positive showed differential methylation of genes including Interleukin 10 Receptor, alpha (IL10RA), Interleukin 17 F (IL17F) and host defence peptides (DEFB and BDEF109). This study has identified a number of immune gene loci at which differential methylation is associated with SICTT test results and the degree of methylation could influence effective host immune responses.


Subject(s)
DNA Methylation , Tuberculin Test , Tuberculosis, Bovine , Cattle , Animals , Tuberculosis, Bovine/genetics , Tuberculosis, Bovine/diagnosis , Tuberculosis, Bovine/immunology , Tuberculin Test/veterinary , Mycobacterium bovis/immunology , Epigenesis, Genetic , Promoter Regions, Genetic
11.
BMJ Open ; 14(8): e085614, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39122402

ABSTRACT

INTRODUCTION: The large reservoir of tuberculosis (TB) infections is one of the main reasons for the persistent incidence of TB. Accurate diagnostic tests are crucial to correctly identify and treat people with TB infection, which is vital to eliminate TB globally. The rdESAT-6 and rCFP-10 (Cy-Tb) injection ('Cy-Tb'), a TB-specific antigen skin test and STANDARD F TB-Feron FIA ('Standard F TB') measuring interferon-gamma by fluorescence immunoassay assay are two novel tools for the diagnosis of TB infection which offer advantages compared with current tests in low-resource settings and reduced costs to both health systems and TB-affected people. The proposed study aims to evaluate the diagnostic accuracy of these two new tests for TB infection diagnosis. METHODS AND ANALYSIS: This cross-sectional study aims to assess the diagnostic accuracy for TB infection of the Cy-Tb skin test and Standard F TB assay (investigational tests) compared with the QuantiFERON-TB Gold Plus (QFT-Plus) assay as the immunological reference standard. Three different cohorts of study participants will be recruited at the Vietnam National Lung Hospital: adults with bacteriologically confirmed pulmonary TB (n=100), household contacts of people with TB (n=200) and people without TB infection (n=50). All consenting participants will undergo simultaneous testing with Cy-Tb, Standard F TB and QFT-Plus. The primary endpoint is the diagnostic accuracy of the Cy-Tb skin test and Standard F TB assay, expressed as sensitivity and specificity against the reference standard. ETHICS AND DISSEMINATION: Ethical approval was granted by the Vietnam National Lung Hospital Institutional Review Board (65/23/CN-HDDD-BVPTU) and the Swedish Ethical Review Authority (Dnr 2023-04271-01). Study results will be disseminated to the scientific community and policymakers through scientific publications. TRIAL REGISTRATION NUMBER: NCT06221735.


Subject(s)
Interferon-gamma Release Tests , Tuberculin Test , Tuberculosis , Adult , Humans , Antigens, Bacterial/analysis , Cross-Sectional Studies , Interferon-gamma Release Tests/methods , Mycobacterium tuberculosis/isolation & purification , Mycobacterium tuberculosis/immunology , Sensitivity and Specificity , Tuberculin Test/methods , Tuberculosis/diagnosis , Tuberculosis, Pulmonary/diagnosis , Vietnam , Research Design
12.
Clin Infect Dis ; 79(3): 751-760, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39036871

ABSTRACT

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) reduces the risk of TB disease in people with human immunodeficiency virus (HIV), yet uptake has been suboptimal in many countries. We assessed whether QuantiFERON Gold In-Tube (QGIT) during routine HIV care increased TB infection (TBI) testing and TPT prescriptions. METHODS: This parallel-arm, 1:1 cluster-randomized controlled trial compared the standard-of-care tuberculin skin test to QGIT in South Africa. We enrolled consenting, TPT-eligible adults diagnosed with HIV ≤30 days prior and used intention-to-treat analyses for the outcomes: proportion of patients with documented TBI results, proportion with documented TPT, and time from enrollment to outcomes. FINDINGS: We enrolled 2232 patients across 14 clinics from November 2014 to May 2017 (58% in intervention clinics). At 24 months of follow-up, more participants in intervention clinics had TBI results (69% vs 2%, P < .001) and TPT prescriptions (45% vs 30%, P = .13) than control clinics. Controlling for baseline covariates, intervention clinics had 60% (95% confidence interval, 51-68; P < .001) more participants with TBI results and 12% (95% confidence interval, -6 to 31; P = .18) more with TPT prescriptions. Among participants with results, those in intervention clinics received results and TPT faster (intervention: median of 6 and 29 days after enrollment vs control: 21 and 54 days, respectively). INTERPRETATION: In this setting, QGIT in routine HIV care resulted in more patients with TBI results. Clinicians also initiated more people with HIV on TPT in QGIT intervention clinics, and did so more quickly, than the control arm. CLINICAL TRIALS REGISTRATION: NCT02119130.


Subject(s)
HIV Infections , Tuberculin Test , Tuberculosis , Humans , Male , South Africa/epidemiology , Female , Adult , Tuberculin Test/methods , Tuberculosis/prevention & control , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Interferon-gamma Release Tests/methods , Middle Aged , Antitubercular Agents/therapeutic use , Antitubercular Agents/administration & dosage
13.
Sci Rep ; 14(1): 17693, 2024 07 31.
Article in English | MEDLINE | ID: mdl-39085338

ABSTRACT

Currently, interferon-gamma release assay (IGRA) is costly and not included as latent tuberculosis infection (LTBI) screening test strategy in Thailand's Universal Coverage Scheme (UCS) benefit package. The objective of this study was to assess the cost-utility of LTBI screening strategies among tuberculosis (TB) contacts in Thailand. A hybrid decision tree and Markov model was developed to compare the lifetime costs and health outcomes of tuberculin skin test (TST) and IGRA, in comparison to no screening, based on a societal perspective. Health outcomes were the total number of TB cases averted and quality-adjusted life years (QALYs), with results presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to explore uncertainties in all parameters. The ICER of TST compared with no screening was 27,645 baht per QALY gained, while that of IGRA compared to TST was 851,030 baht per QALY gained. In a cohort of 1000 TB contacts, both TST and IGRA strategies could avert 282 and 283 TB cases, respectively. At the Thai societal willingness-to-pay threshold of 160,000 baht per QALY gained, TST was deemed cost-effective, whereas IGRA would not be cost-effective, unless the cost of IGRA was reduced to 1,434 baht per test.


Subject(s)
Cost-Benefit Analysis , Interferon-gamma Release Tests , Latent Tuberculosis , Tuberculin Test , Tuberculosis, Pulmonary , Humans , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Latent Tuberculosis/economics , Thailand/epidemiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/economics , Tuberculin Test/economics , Interferon-gamma Release Tests/economics , Male , Female , Quality-Adjusted Life Years , Adult , Middle Aged , Mass Screening/economics , Mass Screening/methods , Markov Chains
15.
Int J Tuberc Lung Dis ; 28(7): 335-342, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38961548

ABSTRACT

BACKGROUNDWHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.OBJECTIVETo evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.METHODSWe developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).RESULTSThe no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.CONCLUSIONSFor PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario..


Subject(s)
Alcohol Drinking , Antitubercular Agents , HIV Infections , Isoniazid , Latent Tuberculosis , Humans , Isoniazid/administration & dosage , Antitubercular Agents/administration & dosage , Antitubercular Agents/adverse effects , Uganda/epidemiology , Latent Tuberculosis/drug therapy , Male , HIV Infections/drug therapy , Female , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Adult , Markov Chains , Tuberculin Test , Tuberculosis/prevention & control , Tuberculosis/epidemiology , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/epidemiology , Young Adult , Middle Aged
16.
Stud Health Technol Inform ; 315: 52-57, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39049225

ABSTRACT

Despite widespread adoption and maturity, paper persistence endures in many Electronic Health Record (EHR) systems, particularly for complex workflows involving multiple steps from different stakeholders separated in time. In our health system, Latent Tuberculosis Infection (LTBI) testing was one such workflow where a Tuberculin Skin Test (TST) must be administered and then correctly read 48-72 hours later and documented. This paper discusses a low-resource workflow analysis and clinical decision support approach to replace a paper workflow and garner the benefits of the EHR for clearer documentation and retrieval of LTBI results. Our approach resulted in a significant increase in completed TST documentation, 57% (24/42) to 95% (18/19), P < 0.003. Human-centered design practices such as work system analysis and formative usability testing are feasible with limited resources and improve the likelihood of success of electronic workflows by designing solutions that fit existing clinical workflows and automating processes wherever possible.


Subject(s)
Decision Support Systems, Clinical , Electronic Health Records , Tuberculin Test , Workflow , Humans , Latent Tuberculosis/diagnosis , Paper , Documentation
17.
Eur Respir Rev ; 33(173)2024 Jul.
Article in English | MEDLINE | ID: mdl-39048129

ABSTRACT

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Following infection, immune responses to Mtb antigens can be measured using the tuberculin skin test or an interferon-γ release assay. The gain of Mtb immunoreactivity, a change from a negative to a positive tuberculin skin test or interferon-γ release assay result, is called conversion and has long been used as a measure of Mtb exposure. However, the loss of immunoreactivity (reversion; a positive followed by a negative result) has often been overlooked. Instead, in clinical and epidemiological circles, Mtb immunoreactivity is commonly considered to persist lifelong and confer a lifetime of disease risk. We present a critical review, describing the evidence for reversion from cohort studies, ecological studies and studies of TB progression risk. We outline the inconsistent reasons why reversion has been dismissed from common understanding and present evidence demonstrating that, just as conversion predominantly indicates prior exposure to Mtb antigens, so its opposite, reversion, suggests the reduction or absence of exposure (endogenous or exogenous). Mtb immunoreactivity is dynamic in both individuals and populations and this is why it is useful for stratifying short-term TB progression risk. The neglect of reversion has shaped TB research and policy at all levels, influencing clinical management and skewing Mtb infection risk estimation and transmission modelling, leading to an underestimation of the contribution of re-exposure to the burden of TB, a serious oversight for an infectious disease. More than a century after it was first demonstrated, it is time to incorporate reversion into our understanding of the natural history of TB.


Subject(s)
Interferon-gamma Release Tests , Mycobacterium tuberculosis , Predictive Value of Tests , Tuberculin Test , Tuberculosis , Humans , Mycobacterium tuberculosis/immunology , Tuberculosis/immunology , Tuberculosis/microbiology , Tuberculosis/epidemiology , Tuberculosis/diagnosis , Risk Factors , Host-Pathogen Interactions , Antigens, Bacterial/immunology , Risk Assessment , Disease Progression , Prognosis , Biomarkers/blood , Time Factors
19.
Przegl Epidemiol ; 78(1): 22-26, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38904309

ABSTRACT

INTRODUCTION: Tuberculosis (TB) is a significant global health concern, particularly in developing countries. Diagnosing latent tuberculosis infection (LTBI) in hemodialysis patients is crucial because of the risk of developing active tuberculosis in this population due to attenuated immune response. Herein, we assessed the prevalence of LTBI in hemodialysis patients. METHODS: In this cross-sectional study, we included all patients referred to hemodialysis centers in Kohgiluyeh and Boyer-Ahmad Province, southwest Iran, in 2018 through census sampling. Tuberculin skin test (TST) was utilized to screen the patients for LTBI. All steps were done by trained physicians. RESULTS: In total, 183 patients (mean age: 59.3, SD= 16.0) were included in the study of which 76 (41.5%) were females, and 107 (58.5%) were males. Neither the patients nor their family members had a history of tuberculosis. Assuming an above 5-millimeter enduration as a positive TST result, 22 patients (12%) had LTBI. None of the demographic or clinical features differed between TST -negative and -positive groups. CONCLUSION: Hemodialysis patients are prone to LTBI due to several immunological and environmental factors. Screening for LTBI may be beneficial to prevent active tuberculosis in this population.


Subject(s)
Latent Tuberculosis , Renal Dialysis , Tuberculin Test , Humans , Female , Male , Iran/epidemiology , Latent Tuberculosis/epidemiology , Latent Tuberculosis/diagnosis , Renal Dialysis/adverse effects , Prevalence , Middle Aged , Risk Factors , Cross-Sectional Studies , Adult , Aged , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/epidemiology
20.
Vet Immunol Immunopathol ; 273: 110788, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38838485

ABSTRACT

Bovine tuberculosis (bTB) represents a threat to livestock production. Mycobacterium bovis is the main causative agent of bTB and a pathogen capable of infecting wildlife and humans. Eradication programs based on surveillance in slaughterhouses with mandatory testing and culling of reactive cattle have failed to eradicate bTB in many regions worldwide. Therefore, developing effective tools to control this disease is crucial. Using a computational tool, we identified proteins in the M. bovis proteome that carry predictive binding peptides to BoLADRB3.2 and selected Mb0309, Mb1090, Mb1810 and Mb3810 from all the identified proteins. The expression of these proteins in a baculovirus-insect cell expression system was successful only for Mb0309 and Mb3810. In parallel, we expressed the ESAT-6 family proteins EsxG and EsxH in this system. Among the recombinant proteins, Mb0309 and EsxG exhibited moderate performance in distinguishing between cattle that test positive and negative to bTB using the official test, the intradermal tuberculin test (IDT), when used to stimulate interferon-gamma production in blood samples from cattle. However, when combined as a protein cocktail, Mb0309 and EsxG were reactive in 50 % of positive cattle. Further assessments in cattle that evade the IDT (false negative) and cattle infected with Mycobacterium avium paratuberculosis are necessary to determine the potential utility of this cocktail as an additional tool to assist the accurate diagnosis of bTB.


Subject(s)
Antigens, Bacterial , Mycobacterium bovis , Tuberculosis, Bovine , Mycobacterium bovis/immunology , Animals , Cattle , Antigens, Bacterial/immunology , Tuberculosis, Bovine/immunology , Bacterial Proteins/immunology , Bacterial Proteins/genetics , Tuberculin Test/veterinary , Recombinant Proteins/immunology , Recombinant Proteins/genetics
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