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Objective: This study aimed to investigate the prevalence of paratuberculosis in cattle and buffaloes at twelve public dairy farms in Punjab, Pakistan. Methods: A total of 2,181 more than two-year-old animals (1,242 cattle and 939 buffaloes) were tested by avian tuberculin, i.e., killed purified protein derivative of Mycobacterium avium paratuberculosis and indirect enzyme linked immunosorbent assay (ELISA). Blood and fecal samples were collected from tuberculin positive animals. These samples were further processed by indirect ELISA. The data were analyzed using frequency analysis and logistic analysis procedures. Results: The prevalence of paratuberculosis at public dairy farms was 3.8%, as determined by tuberculin+ELISA test. It varied from 0.71% to 13.5% with a 100% herd prevalence. Multivariate logistic regression analysis revealed that species, milk production, total animals, total small ruminants, and total buffaloes were significantly associated with the occurrence of paratuberculosis. Odd ratio analysis revealed that with a one-kilogram increase in body weight, there will be a 0.006% increase in disease occurrence. With the increase in one animal in small ruminants and buffaloes, there will be 0.008% and 0.42% greater chances of developing paratuberculosis, respectively. Bivariate logistic regression analysis of cattle and buffaloes revealed that farm number, age, and total number of cattle were significantly associated with the occurrence of paratuberculosis. A one-month increase in lactation length increases the chance of tuberculosis by 0.004%; similarly, a one-liter increase in milk production increases the chance of disease by 10%. With each additional buffalo in the herd, there will be a 0.007% greater chance for the occurrence of paratuberculosis. Conclusion: This study concluded that tuberculin testing can be used in conjunction with ELISA to screen animals for paratuberculosis in countries with scarce resources, such as Pakistan. The efficacy of disease diagnosis can be improved by combining multiple tests. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Most paediatric tuberculosis (TB) cases in low-TB-incidence countries involve children born to migrant families. This may be partially explained by trips to their countries of origin for visiting friends and relatives (VFR). We aimed to estimate the risk of latent TB infection (LTBI) and TB in children VFR. Methods We conducted a prospective multicentric observational study in Catalonia (Spain) from June 2017 to December 2019. We enrolled children aged < 15 years with a negative tuberculin skin test (TST) at baseline and at least one parent from a high-TB-incidence country, and who had travelled to their parent's birth country for ≥21 days. TST and QuantiFERON-TB Gold Plus (QFT-Plus) were performed within 8–12 weeks post-return. LTBI was defined as a TST ≥5 mm and/or a positive QFT-Plus. Results Five hundred children completed the study, equivalent to 78.2 person-years of follow-up (PYFU). Thirteen children (2.6%) were diagnosed with LTBI (16.6/per100 PYFU, 95%CI = 8.8–28.5), including two cases (0.4%) of TB (2.5/per100 PYFU, 95%CI = 0.3–9.3). LTBI incidence rates remained high after excluding BCG-vaccinated children (9.7/per100 PYFU, 95%CI = 3.9–20.0). Household tobacco smoke exposure was associated with LTBI (aOR = 3.9, 95%CI = 1.1–13.3). Conclusions The risk of LTBI in children VFR in high-TB-incidence countries may equal, or perhaps even exceed, the infection risk of the native population. The primary associated risk factor was the presence of smokers in the household. Furthermore, the incidence rate of active TB largely surpassed that of the countries visited. Children VFR in high-TB-incidence countries should be targeted for diagnostic and preventive interventions. [ABSTRACT FROM AUTHOR]

Aims and Obctives: To compare FNAC, microscopy (ZN staining), histopathology and CBNAAT for diagnosis of head and neck tuberculosis, and to evaluate efficacy of CBNAAT in early diagnosis of tuberculosis in head and neck region. Materials and methods: This prospective study was carried out in the department of otorhinolaryngology, JLN Medical College and attached hospital, Ajmer from August 2020 to September 2022. Thorough history and clinical examination of all patients presented with neck swelling was done. All relevant investigations including chest x-ray, mantoux test, ESR, FNAC, ZN staining, CBNAAT and histopathology were done and their efficacy was compared. Results: Sensitivity and specificity of CBNAAT in detecting extra pulmonary tuberculosis was 85.19% and 91.30% respectively, and diagnostic accuracy was consistent with findings of FNAC and ZN staining (p < 0.001) for diagnosis of cervical lymphadenopathy. Conclusion: CBNAAT has a promising role in early diagnosis of head and neck tuberculosis as well as other cases of smear negative tuberculosis such as MDR TB and TB-HIV and is optimal for the diagnosis of lymph node tuberculosis and helps in early identification and initiation of treatment. Sensitivity of CBNAAT scored twice as high in comparison with microscopy thus doubling the proportion of rapid diagnoses with important effect on the patient's outcome. [ABSTRACT FROM AUTHOR]

In the context of the evolving global health landscape shaped by the COVID-19 pandemic, tuberculosis (TB) is gaining renewed attention as a reemerging threat even in low-endemic countries. Immunological tests such as the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) are pivotal in identifying tuberculosis infection (TBI). However, their inability to distinguish between past and ongoing infection poses a diagnostic challenge, possibly leading to the unnecessary treatment of a significant portion of the population with potential side effects. This review delves into the concept of incipient tuberculosis (ITB), a dynamic, presymptomatic stage characterized by heightened Mycobacterium tuberculosis complex (MTC) metabolic activity and replication that result in minimal radiological changes, signifying a transitional state between TBI and TB. Key focus areas include epidemiological factors, underlying pathogenesis, imaging findings, and the ongoing challenges in the identification of individuals with ITB through the development of new biomarkers and the use of whole-genome sequencing-based analyses to implement early treatment strategies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effectiveness of an improved screening strategy for tuberculosis (TB) infection rates in schools. Methods A total of 29 765 students from junior high and senior high grades in urban areas of the city were included from 2018 to 2019. Conventional methods were used for TB infection screening in the control group, while an improved method was implemented in the observation group. From 2020 to 2022,47 082 students were screened using the improved method. Positive rates of TB infection screening were statistically analyzed. Results The TB infection positive rate was higher in the observation group compared to the control group, with a significant difference (P<0.05). From 2018 to 2022, there was a gradual decrease in TB infection positivity rates. Scores for TB prevention and treatment knowledge among students and healthcare workers increased significantly after training sessions (P<0.05). Scores showed an increasing trend over the years for both groups. Conclusion The improved screening method effectively increased the TB infection screening positivity rate, enhanced TB prevention and treatment knowledge among students and healthcare workers, and contributed to a decrease in TB infection rates, thereby effectively controlling tuberculosis infections. [ABSTRACT FROM AUTHOR]

Background In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe. Methods Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000–2020. Results A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P =.013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P <.001; odds ratio [95% confidence interval], 2.073 [1.37–3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P <.001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P <.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P =.083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P =.004). Conclusions Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies. [ABSTRACT FROM AUTHOR]

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OBJECTIVE: Present an approach to the safe and efficient provision of anesthesia and birth control measures to a large group of primates. ANIMALS: 98 hamadryas baboons (Papio hamadryas) held in a German zoological institution. METHODS: A group of 12 veterinarians, 2 zookeepers, and 6 volunteers anesthetized all animals within 2 days. The baboons were orally premedicated with midazolam (0.1 to 0.5 mg/kg) and anesthetized with medetomidine (40 to 60 μg/kg, IM) and ketamine (2 to 4 mg/kg, IM); isoflurane at rates of 1.5% to 2% was used for maintaining anesthesia if necessary. All animals received a physical examination, prophylactic medication, and tuberculin testing. For population management, the animals received a contraceptive implant (adult females), orchiectomy (young males), or vasectomy (breeding males). Young males received intratesticular blocks with lidocaine. All animals received atipamezole (125 to 150 μg/kg) before recovery. RESULTS: Premedication resulted in anxiolysis, which facilitated separating and darting. Median time from darting to access to the animal was 10 minutes. Mean anesthetic times were 25 minutes for females and 55 minutes for males. The depth of anesthesia was appropriate for the procedures. No fatalities were recorded. One animal was injured by other baboons but recovered after treatment. CLINICAL RELEVANCE: Health management and birth control measures are necessary in baboon troops under human care. Anesthesia and/or contraception of individual animals often leads to intraspecific aggression. This case series describes how to provide anesthesia and contraception to an entire troop as an alternative approach that can be adopted to future similar interventions. [ABSTRACT FROM AUTHOR]

Early identification of Mycobacterium strains that cause TB (Tuberculosis) is crucial in preventing tuberculosis illness. Conventional medical diagnostics, such as PPD (tuberculin skin tests) tests and antibody-assisted tests, have low sensitivity, extensive processing times, and complex post-test procedures. These problems minimize its potential and drive innovation in tuberculosis diagnosis. Biosensors have simplified the identification of illnesses by reducing the time between sample and results. This paper proposes a circular ring-shaped refractive index sensor for the identification of the four different types of mycobacterium tuberculosis cells. This sensor has achieved the highest sensitivity of 1500 nm/RIU for all four types of tb cells by analyzing the different parameters like substrate height, resonator height, radius of the circle, length of the substrate, and width of the circle resonator. It covers the wavelength range of 2000 nm to 2050 nm. The highest value of the quality factor has been observed is 40,280 for TBC2 (Tuberculosis cell 2, specific type of tuberculosis) and the highest value of the figure of merit has been observed is 30,000 for TBC2 compared to normal cells. The best response for the DL (Detection limit) has been observed at 0.000005 for TBC2. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ObjectivesTo 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.MethodsTB 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).ResultsContacts with index TB patients with sputum smear >1+ was associated with positive QFT-Plus compared to those without (p

Objective This study aimed to investigate the prevalence of paratuberculosis in cattle and buffaloes at twelve public dairy farms in Punjab, Pakistan. Methods A total of 2,181 more than two-year-old animals (1,242 cattle and 939 buffaloes) were tested by avian tuberculin, i.e., killed purified protein derivative of Mycobacterium avium paratuberculosis and indirect enzyme linked immunosorbent assay (ELISA). Blood and fecal samples were collected from tuberculin positive animals. These samples were further processed by indirect ELISA. The data were analyzed using frequency analysis and logistic analysis procedures. Results The prevalence of paratuberculosis at public dairy farms was 3.8%, as determined by tuberculin+ELISA test. It varied from 0.71% to 13.5% with a 100% herd prevalence. Multivariate logistic regression analysis revealed that species, milk production, total animals, total small ruminants, and total buffaloes were significantly associated with the occurrence of paratuberculosis. Odd ratio analysis revealed that with a one-kilogram increase in body weight, there will be a 0.006% increase in disease occurrence. With the increase in one animal in small ruminants and buffaloes, there will be 0.008% and 0.42% greater chances of developing paratuberculosis, respectively. Bivariate logistic regression analysis of cattle and buffaloes revealed that farm number, age, and total number of cattle were significantly associated with the occurrence of paratuberculosis. A one-month increase in lactation length increases the chance of tuberculosis by 0.004%; similarly, a one-liter increase in milk production increases the chance of disease by 10%. With each additional buffalo in the herd, there will be a 0.007% greater chance for the occurrence of paratuberculosis. Conclusion This study concluded that tuberculin testing can be used in conjunction with ELISA to screen animals for paratuberculosis in countries with scarce resources, such as Pakistan. The efficacy of disease diagnosis can be improved by combining multiple tests.

Background Tuberculosis (TB) is an infectious disease that is still a common threat worldwide, especially in pediatric populations. TB transmission occurs particularly when the transmitter has no obvious manifestation of the disease. There is a higher incidence of TB infection in children than in the general population, especially in high risk populations such as children in orphanages. However, the incidence of TB infection in orphaned children in Indonesia, including Bali, is unknown. Objective To describe the incidence and risk factors for TB infection in children in orphanages in Bali. Methods This case-control study was conducted in 12 orphanages in Bali. Subjects were divided into a case group comprised of children with TB infection, and a control group comprised of those without TB infection. TB infection was diagnosed by positive tuberculin test without clinically confirmed TB. Results A total of 175 children were recruited as subjects. There were 49 (28.0%) children with TB infection. Bivariate analysis revealed significant associations between density, humidity, ventilation/room area ratio, and area of ??origin with TB infection. Multivariate analysis showed that ventilation/room area ratio and room humidity of ?73% were independently positive correlated with TB infection. Natural lighting and BCG scar were not significantly different between groups. Conclusion The occurence of TB infection in children residing in orphanages in Bali is high (28%). The risk factors identified independently are lower ventilation and higher room humidity.

Background: Granuloma annulare is a noninfectious inflammatory granulomatous skin disease characterized by an erythematous or skin colored annulare plaque. The diagnosis of granuloma annulare may be challenging owing to its diverse morphology. In such cases, a correlation between the clinical findings and histologic findings are necessary. Case presentation: We report a case of granuloma annulare after purified protein derivative administration. A 56-year-old Caucasian female patient complained of mildly pruritic rashes which started on both arms and lower extremities, and eventually spread to both thighs, the left popliteal region, left upper back, and the right abdominal area. About 6 weeks prior to the eruption of the rashes, the patient had been given a purified protein derivative tuberculin skin test. Biopsy specimens revealed dermal histiocytes palisading around areas of mucin and degenerated collagen, confirming granuloma annulare. After treatment with 0.1% topical triamcinolone acetanide and 500 mg oral metronidazole, the patient's lesions resolved. Discussion: Relatively little is known about granuloma annulare's exact etiology. Granuloma annulare has four variations presenting as either localized, generalized, subcutaneous, or perforating and patch granuloma annulare. The clinical prognosis for granuloma annulare varies according to clinical subtypes. Proposed causal mechanisms of subcutaneous granuloma annulare include physical trauma, infections, immunizations, insect bites, diabetes mellitus, and alterations in the cell-mediated immune responses. The disease likely has an inflammatory component. Clinically, granuloma annulare may be confused with many other skin diseases. Conclusion: This case of subcutaneous granuloma annulare was reported since it is a rare dermatologic pathological condition that can be confused with other skin rash disorders. Although it is a benign self-limited disease, definitive diagnosis is important to rule out other pathologies with similar clinical appearances, such as cancer or human immunodeficiency virus (HIV) infection. Diagnostic confirmation is best made through skin biopsy. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear. Methods In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering. Results Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]:.57–.92, P =.005). In pre-specified analyses, the effect was largest among children aged 5–11 years and males. Conclusions A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions. [ABSTRACT FROM AUTHOR]

The persistent threat of tuberculosis (TB) on a global scale hasprompted a reevaluation of preventive strategies, with a particular focus onthe Bacille Calmette‐Guérin (BCG) vaccine's role in revaccination. Theresurgence underscores an urgent need for enhanced measures, prompting acritical examination of BCG revaccination strategies. Drawing from the researchof Paulo Cesar Pereira dos Santos and a synthesis of randomized controlledtrials (RCTs), this review identifies key considerations for refining BCGrevaccination's efficacy against Mycobacterium tuberculosis (MTB) andTB. The main body of this review integrates four principal domains essentialfor optimizing BCG revaccination: the timing of revaccination, the assessmentof various BCG strains, the evaluation of the vaccine's effectiveness on MTBand non‐tuberculous mycobacteria (NTM) strains, and the enhancement of RCTmethodologies. Determining the optimal revaccination timing is paramount forbolstering immunity, especially in regions with high TB prevalence. Theanalysis of different BCG strains provides insights into strain‐specificimmunogenicity, informing vaccine deployment strategies. Additionally,understanding the vaccine's impact on a range of mycobacterial infections iscrucial for its broader application in various microbial contexts. The reviewemphasizes the refinement of RCT designs to ensure robust and consistentoutcomes, facilitating the reproducibility of results in diverse settings. Itproposes a strategy that not only suggests modifications to revaccinationpractices to increase global TB prevention effectiveness but also calls forcontinuous research to improve BCG revaccination methodologies. The paperadvocates for a standardized, evidence‐driven approach to global TB preventionthat takes into account regional epidemiological differences. In conclusion,this review significantly contributes to the discourse on TB prevention,advocating for evidence‐based, standardized approaches that could potentiallytransform the role of BCG revaccination in global TB prevention efforts. Thefindings support current initiatives aimed at developing policies based onsolid evidence, ensuring the scientific integrity and practical relevance ofBCG revaccination strategies. [ABSTRACT FROM AUTHOR]

The accurate diagnosis of tuberculosis (TB) in children is essential for its effective management and control. Reliable diagnostic tools that are currently available for identifying TB infection include the in vivo tuberculosis skin test (TST) and ex vivo interferon-gamma release assays (IGRAs). This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of IGRAs in children. Of the 768 screened studies, 47 met the eligibility criteria. Data from 9065 patients, including 1086 (12.0 %) with confirmed TB, were included in the analysis. The overall quality of the included studies, assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, was unclear. The calculated pooled sensitivity and specificity of IGRAs in children were 0.85 (95 % confidence interval [CI]: 0.79–0.89) and 0.94 (95 % CI: 0.88–0.97), respectively. Subpopulation analysis revealed that the sensitivities and specificities were as follows: QuantiFERON tests: 0.83 (95 % CI: 0.74–0.89) and 0.93 (95 % CI: 0.87–0.96), T-SPOT: 0.87 (95 % CI: 0.79–0.91) and 0.99 (95 % CI: 0.85–1.00), IGRAs in children under 15 years: 0.77 (95 % CI: 0.43–0.94) and 0.96 (95 % CI: 0.84–0.97), and IGRAs in children under 5 years: 0.85 (95 % CI: 0.52–0.97) and 0.94 (95 % CI: 0.90–0.99), respectively. This study demonstrated that the sensitivity and specificity of the IGRAs in children were moderate and high, respectively. Therefore, the IGRAs may be useful for detecting TB infection in children. The review protocol was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000046737). [ABSTRACT FROM AUTHOR]

Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT. This partially blinded, parallel-arm, non-inferiority, randomised, controlled, phase 2b trial was done at seven university-affiliated clinics in Canada, Indonesia, and Viet Nam. Participants aged 10 years or older were included if they had an indication for TPT according to WHO guidelines for Indonesia and Viet Nam, or Canadian guidelines for Canadian sites, and a positive tuberculin skin test or interferon-γ release assay. Participants were randomly assigned (1:1:1) to receive oral rifampicin at 10 mg/kg once daily for 4 months (standard-dose group), 20 mg/kg daily for 2 months (20 mg/kg group), or 30 mg/kg daily for 2 months (30 mg/kg group). The randomisation sequence was computer generated with blocks of variable size (three, six, and nine) and stratified by country for Indonesia and Viet Nam, and by city within Canada. Participants and investigators were masked to dose in high-dose groups, but unmasked to duration in all groups. The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and treatment completion (in the modified intention-to-treat [mITT] population, excluding those ineligible after randomisation). Protocol-defined adverse events were defined as grade 3 or worse, or rash or allergy of any grade, judged by an independent and masked panel as possibly or probably related to the study. A margin of 4% was used to assess non-inferiority. This study is registered with ClinicalTrials.gov , NCT03988933 (active). Between Sept 1, 2019, and Sept 30, 2022, 1692 people were assessed for eligibility, 1376 were randomly assigned, and eight were excluded after randomisation. 1368 participants were included in the mITT population (454 in the standard group, 461 in the 20 mg/kg group, and 453 in the 30 mg/kg group). 589 (43%) participants were male and 779 (57%) were female. 372 (82%) in the standard-dose group, 329 (71%) in the 20 mg/kg group, and 293 (65%) in the 30 mg/kg group completed treatment. No participants in the standard-dose group, one (<1%) of 441 participants in the 20 mg/kg group, and four (1%) of 423 in the 30 mg/kg group developed grade 3 hepatotoxicity. Risk of protocol-defined adverse events was higher in the 30 mg/kg group than in the standard-dose group (adjusted risk difference 4·6% [95% CI 1·8 to 7·4]) or the 20 mg/kg group (5·1% [2·3 to 7·8]). There was no difference in the risk of adverse events between the 20 mg/kg and standard-dose groups (–0·5% [95% CI –2·4 to 1·5]; non-inferiority met). Completion was lower in the 20 mg/kg group (–7·8% [95% CI –13·6 to –2·0]) and the 30 mg/kg group (–15·4% [–21·4 to –9·4]) than in the standard-dose group. In this trial, 2 months of 30 mg/kg daily rifampicin had significantly worse safety and completion than 4 months of 10 mg/kg daily and 2 months of 20 mg/kg daily (the latter, a fully blinded comparison); we do not consider 30 mg/kg to be a good option for TPT. Rifampicin at 20 mg/kg daily for 2 months was as safe as standard treatment, but with lower completion. This difference remains unexplained. Canadian Institutes of Health Research. [ABSTRACT FROM AUTHOR]

Ante-mortem diagnosis of bovine tuberculosis (bTB) is based mainly on the tuberculin skin test (TST) and the ...-IFN release assay (IGRA). Some infected animals escape screening tests, thus, limit herd sanitation. Previous reports have suggested a predominant pattern of multi-organ lesions attributable to Mycobacterium bovis (the causative agent of bTB) bacteraemia. A case--control study was conducted to investigate blood PCR as an alternative tool for improving ante-mortem detection of TST false-negative bovines. Cases comprised 70 TST false-negative bovines (cases), which were serology positive, and controls included 81 TST positive bovines; all of them confirmed as infected with M. bovis. Detection of the IS6110 target through touchdown blood-PCR (IS6110 TD-PCR) was performed. The positivity of the blood-PCR was 27.2% in the control group. This performance was similar to the 15% obtained among cases (p = 0.134). Most cases identified by the IS6110 TD-PCR exhibited focalized lesions (p = 0.002). Results demonstrated that blood-PCR could detect TST false-negative cattle, even if they are negative for IGRA. Considering that cases exhibited humoral response to M. bovis, further studies conducted in a pre-serological stage could provide evidence about the real contribution of the technique in herds. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Tuberculosis (TB) is a public health threat, with >80% of active TB in the United States occurring due to reactivation of latent TB infection (LTBI). We may be underscreening those with high risk for LTBI and overtesting those at lower risk. A better understanding of gaps in current LTBI testing practices in relation to LTBI test positivity is needed. Methods This study, conducted between 1 January 2008 and 31 December 2019 at Kaiser Permanente Southern California, included individuals aged ≥18 years without a history of active TB. We examined factors associated with LTBI testing and LTBI positivity. Results Among 3 816 884 adults (52% female, 37% White, 37% Hispanic, mean age 43.5 years [standard deviation, 16.1]), 706 367 (19%) were tested for LTBI, among whom 60 393 (9%) had ≥1 positive result. Among 1 211 971 individuals who met ≥1 screening criteria for LTBI, 210 025 (17%) were tested for LTBI. Factors associated with higher adjusted odds of testing positive included male sex (1.32; 95% confidence interval, 1.30–1.35), Asian/Pacific Islander (2.78, 2.68–2.88), current smoking (1.24, 1.20–1.28), diabetes (1.13, 1.09–1.16), hepatitis B (1.45, 1.34–1.57), hepatitis C (1.54, 1.44–1.66), and birth in a country with an elevated TB rate (3.40, 3.31–3.49). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing. Conclusions Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to refine and implement screening guidelines that appropriately target testing for those at highest risk for LTBI. [ABSTRACT FROM AUTHOR]

Background: Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB. Methods: A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity. Results: Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3–3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors. Conclusion: Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Latent tuberculosis infection (LTBI) screening is strongly recommended in the pre-transplant evaluation of solid organ transplant (SOT) recipients, although it remains inadequate in many transplant centers. We decided to investigate pre-transplant TB risk assessment, LTBI treatment, and registry rates in Türkiye. MATERIAL AND METHODS: Adult SOT recipients who underwent tuberculin skin test (TST) and/or interferon-gamma release test (IGRA) from 14 centers between 2015 and 2019 were included in the study. An induration of ≥5 mm on TST and/or probable/positive IGRA (QuantiFERON-TB) was considered positive for LTBI. Demographic features, LTBI screening and treatment, and pre-/post-transplant TB history were recorded from the electronic database of transplantation units across the country and pooled at a single center for a unified database. RESULTS: TST and/or IGRA were performed in 766 (33.8%) of 2266 screened patients most of whom were kidney transplant recipients (n = 485, 63.4%). LTBI screening test was positive in 359 (46.9%) patients, and isoniazid was given to 203 (56.5%) patients. Of the patients treated for LTBI, 112 (55.2%) were registered in the national registry, and 82 (73.2%) completed the treatment. Tuberculosis developed in 6 (1.06%) of 563 patients who were not offered LTBI treatment. CONCLUSION: We determined that overall, only one-third of SOT recipients in our country were evaluated in terms of TB risk, only 1 of the 2 SOT recipients with LTBI received treatment, and half were registered. Therefore, we want to emphasize the critical importance of pretransplant TB risk stratification and registration, guided by revised national guidelines. [ABSTRACT FROM AUTHOR]

To determine the cost-effectiveness of the QuantiFERON-TB Gold Plus (QFT-Plus) test versus the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent subjects in the context of the Colombian healthcare system. A hypothetical cohort of 2000 immunocompetent adults vaccinated with Bacillus Calmette-Guérin at birth who are asymptomatic for tuberculosis disease was simulated and included in a decision tree over a horizon of <1 year. The direct healthcare costs related to tests, antituberculosis treatment, and medical care were considered, and diagnostic performance was used as a measure of effectiveness. The incremental cost-effectiveness ratio (ICER) was estimated, and univariate deterministic and probabilistic sensitivity analyses were carried out using 5000 simulations. The currency was the US dollar for the year 2022, with a cost-effectiveness threshold of $6666 USD (1 gross domestic product per capita for 2022). QFT-Plus was cost-effective with an ICER of $5687 USD for each correctly diagnosed case relative to a threshold of $6666 USD. In the deterministic analysis, QFT-Plus was cost-effective in half of the proposed scenarios. The variable that most affected the ICER was the prevalence of latent tuberculosis and test sensitivities. In the probabilistic analysis, QFT-Plus was cost-effective in 54.74% of the simulated scenarios, and tuberculin skin test was dominant in 13.84%. The study provides evidence of the cost-effectiveness of QFT-Plus compared with the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent adults in the Colombian context. • QuantiFERON-TB Gold Plus and tuberculin skin test are useful in the diagnosis of latent tuberculosis infection in the absence of a gold standard. They have similar diagnostic performance according to some meta-analysis. However, they have not been evaluated in a head-to-head cost-effectiveness study in the Colombian context. • To our knowledge, this is the first study evaluating the cost-effectiveness of QuantiFERON-TB Gold Plus and tuberculin skin test in immunocompetent subjects before starting immunosuppressive therapy from the third payer's perspective in Colombia. In the base case scenario, QuantiFERON-TB Gold Plus has proven to be a cost-effective test. The above was proven in different proposed scenarios in the deterministic and probabilistic sensitivity analyses. • In the base case scenario, tuberculin skin test increased the false-negative results by 105%. Tuberculin skin test was the dominant strategy in 2 situations, when the latent tuberculosis infection prevalence and the QuantiFERON-TB Gold Plus sensitivity were at the lowest values. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis is usually diagnosed using tuberculin skin tests or at post-mortem. Recently, we have developed a serological test for bovine tuberculosis in cattle which shows a high degree of accuracy using serum samples. Here, we have assessed the performance of the test using individual bovine milk samples. The diagnostic specificity estimate using the high sensitivity setting of the test was 99.7% (95% CI: 99.2–99.9). This estimate was not altered significantly by tuberculin boosting. The relative sensitivity estimates of the test using the high sensitivity setting in milk samples from comparative skin test positive animals was 90.8% (95% CI: 87.1–93.6) with boosting. In animals with lesions, the relative sensitivity was 96.0% (95% CI: 89.6–98.7). Analysis of paired serum and milk samples from skin test positive animals showed correlation coefficients ranging from 0.756–0.955 for individual antigens used in the test. Kappa analysis indicated almost perfect agreement between serum and milk results, while McNemar marginal homogeneity analysis showed no statistically significant differences between the two media. The positive and negative likelihood ratio were 347.8 (95% CI: 112.3–1077.5) and 0.092 (95% CI: 0.07–0.13) respectively for boosted samples from skin test positive animals. The results show that the test has high sensitivity and specificity in individual milk samples and thus milk samples could be used for the diagnosis of bovine tuberculosis. [ABSTRACT FROM AUTHOR]

Background: The use of systems engineering tools, including the development and use of care cascades using routinely collected data, process mapping, and continuous quality improvement, is used for frontline healthcare workers to devise systems level change. South Africa experiences high rates of tuberculosis (TB) infection and disease as well as HIV co-infection. The Department of Health has made significant gains in HIV services over the last two decades, reaching their set "90–90-90" targets for HIV. However, TB services, although robust, have lagged in comparison for both disease and infection. The Systems Analysis and Improvement Approach (SAIA) is a five-step implementation science method, drawn from systems engineering, to identify, define, and implement workflow modifications using cascade analysis, process mapping, and repeated quality improvement cycles within healthcare facilities. Methods: This stepped-wedge cluster randomized trial will evaluate the effectiveness of SAIA on TB (SAIA-TB) cascade optimization for patients with TB and high-risk contacts across 16 clinics in four local municipalities in the Sarah Baartman district, Eastern Cape, South Africa. We hypothesize that SAIA-TB implementation will lead to a 20% increase in each of: TB screening, TB preventive treatment initiation, and TB disease treatment initiation during the 18-month intervention period. Focus group discussions and key informant interviews with clinic staff will also be conducted to determine drivers of implementation variability across clinics. Discussion: This study has the potential to improve TB screening, treatment initiation, and completion for both active disease and preventive measures among individuals with and without HIV in a high burden setting. SAIA-TB provides frontline health care workers with a systems-level view of their care delivery system with the aim of sustainable systems-level improvements. Trial registration: Clinicaltrials.gov, NCT06314386. Registered 18 March 2024, https://clinicaltrials.gov/study/NCT06314386. NCT06314386. [ABSTRACT FROM AUTHOR]

Background Tuberculosis (TB) can induce secondary hemophagocytic lymphohistiocytosis (HLH), a severe inflammatory syndrome with high mortality. We integrated all published reports of adult HIV-negative TB-associated HLH (TB-HLH) to define clinical characteristics, diagnostic strategies, and therapeutic approaches associated with improved survival. Methods PubMed, Embase, and Global Index Medicus were searched for eligible records. TB-HLH cases were categorized into (1) patients with a confirmed TB diagnosis receiving antituberculosis treatment while developing HLH and (2) patients presenting with HLH of unknown cause later diagnosed with TB. We used a logistic regression model to define clinical and diagnostic parameters associated with survival. Results We identified 115 individual cases, 45 (39.1%) from countries with low TB incidence (<10/100 000 per year). When compared with patients with HLH and known TB (n = 21), patients with HLH of unknown cause (n = 94) more often had extrapulmonary TB (66.7% vs 88.3%), while the opposite was true for pulmonary disease (91.5% vs 59.6%). Overall, Mycobacterium tuberculosis was identified in the bone marrow in 78.4% of patients for whom examination was reported (n = 74). Only 10.5% (4/38) of patients tested had a positive result upon a tuberculin skin test or interferon-γ release assay. In-hospital mortality was 28.1% (27/96) in those treated for TB and 100% (18/18) in those who did not receive antituberculosis treatment (P <.001). Conclusions Tuberculosis should be considered a cause of unexplained HLH. TB-HLH is likely underreported, and the diagnostic workup of patients with HLH should include bone marrow investigations for evidence of Mycobacerium tuberculosis. Prompt initiation of antituberculosis treatment likely improves survival in TB-HLH. [ABSTRACT FROM AUTHOR]

Functional decline is associated with critical illness, though this relationship in surgical patients is unclear. This study aims to characterize functional decline after intensive care unit (ICU) admission among surgical patients. We performed a retrospective analysis of surgical patients admitted to the ICU in the Cerner Acute Physiology and Chronic Health Evaluation database, which includes 236 hospitals, from 2007 to 2017. Patients with and without functional decline were compared. Predictors of decline were modeled. A total of 52,838 patients were included; 19,310 (36.5%) experienced a functional decline. Median ages of the decline and nondecline groups were 69 (interquartile range 59-78) and 63 (interquartile range 52-72) years, respectively (P < 0.01). The nondecline group had a larger proportion of males (59.1% versus 55.3% in the decline group, P < 0.01). After controlling for sociodemographic covariates, comorbidities, and disease severity upon ICU admission, patients undergoing pulmonary (odds ratio [OR] 6.54, 95% confidence interval [CI] 2.67-16.02), musculoskeletal (OR 4.13, CI 3.51-4.87), neurological (OR 2.67, CI 2.39-2.98), gastrointestinal (OR 1.61, CI 1.38-1.88), and skin and soft tissue (OR 1.35, CI 1.08-1.68) compared to cardiovascular surgeries had increased odds of decline. More than one in three critically ill surgical patients experienced a functional decline. Pulmonary, musculoskeletal, and neurological procedures conferred the greatest risk. Additional resources should be targeted toward the rehabilitation of these patients. [ABSTRACT FROM AUTHOR]

Lupus vulgaris (LV) is a type of paucibacillary cutaneous tuberculosis that can occur due to inoculation, lymphatic, or hematogenous route. It occurs in a previously sensitized individual with high immunity to tuberculosis. LV can have different morphology of presentation, which can lead to difficulty in diagnosis. The Tuberculin test is strongly positive. Histopathology will show epithelioid granulomas in the superficial dermis and acid‐fast bacilli rarely demonstrable within the granulomas. Dermoscopy will show focused linear vessels on a yellow to orange background. Culture is the gold standard for diagnosis, but its positivity rate is low. Mycobacterium tuberculosis bacilli can be detected using polymerase chain reaction from the lesions. Histopathology, tuberculin test, dermoscopy, molecular test, and culture would help diagnose LV. This review discusses the introduction, pathogenesis, clinical features, differential diagnosis, investigations, complications, and treatment of lupus vulgaris in detail. This review can help the dermatologist understand the condition better with appropriate diagnosis and therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Background: Among chronic condition problems, tuberculosis still represents a serious public health problem globally. Objective: To investigate latent tuberculosis infection in patients with Crohn’s disease. Retrospective, descriptive cross-sectional study of quantitative analysis. Methods: The research was conducted on diagnosed cases of Crohn’s disease at the University Hospital located in a city in Northeastern Brazil. All cases of patients with Crohn’s disease undergoing isoniazid or rifampicin therapy for latent tuberculosis (LTBI) were included in the study. The data obtained were subsequently subjected to statistical analysis using the Statistical Package for the Social Sciences (SPSS) program. Results: We analyzed 235 medical records, and it was observed that 56% were male, with a mean age of 42.7. Among these, 54% declared themselves as brown, 31% had completed high school, and 47% were residents of the city of Teresina. Regarding the clinical and epidemiological characteristics of the studied patients classified as having ILTB, 34% of the medical records were diagnosed by tuberculin test, 48.51% were investigated by x-ray examination, and the recent location affected the colon with 27%. Conclusion: Overall, the health profile of the participants in this study aligns with findings previously established in the literature, particularly studies conducted in other Brazilian states, as well as in other developing countries.

Objective: The aim of the study is to compare the prevalence of latent tuberculosis infection and tuberculosis (TB) in the prepandemic period (2017-2019) with the pandemic period (2020-2022), in a group of healthcare workers (HCWs). Methods: This is a retrospective study. Data on TB diagnosis was retrieved from the hospital information system database. All HCWs who underwent tuberculin skin test (TST) from January 2017 to December 2022 were included in the study. Results: In the prepandemic period (2017-2019), 163 HCWs out of 710 were TST positive (22.9%), and in the pandemic period (2020-2022), 85 HCWs out of 449 were TST positive (18.9%) (P = 0.11). There were 10 HCWs diagnosed with TB in the prepandemic period (incidence: 41.7/100,000) and 2 in the pandemic period (incidence: 8.3/100,000) (P < 0.0001). Conclusions: This study showed that TB incidence was reduced during the pandemic period in HCWs. TST positivity was also reduced, though not statistically significant. [ABSTRACT FROM AUTHOR]

BackgroundSocial network analysis can elucidate tuberculosis transmission dynamics outside the home and may inform novel network-based case-finding strategies.MethodsWe assessed the association between social network characteristics and prevalent tuberculosis infection among residents (aged ≥15 years) of 9 rural communities in Eastern Uganda. Social contacts named during a census were used to create community-specific nonhousehold social networks. We evaluated whether social network structure and characteristics of first-degree contacts (sex, human immunodeficiency virus [HIV] status, tuberculosis infection) were associated with revalent tuberculosis infection (positive tuberculin skin test [TST] result) after adjusting for individual-level risk factors (age, sex, HIV status, tuberculosis contact, wealth, occupation, and Bacillus Calmette-Guérin [BCG] vaccination) with targeted maximum likelihood estimation.ResultsAmong 3 335 residents sampled for TST, 32% had a positive TST results and 4% reported a tuberculosis contact. The social network contained 15 328 first-degree contacts. Persons with the most network centrality (top 10%) (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.1]) and the most (top 10%) male contacts (1.5 [1.3-1.9]) had a higher risk of prevalent tuberculosis, than those in the remaining 90%. People with ≥1 contact with HIV (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.6]) and ≥2 contacts with tuberculosis infection were more likely to have tuberculosis themselves (2.6 [ 95% confidence interval: 2.2-2.9]).ConclusionsSocial networks with higher centrality, more men, contacts with HIV, and tuberculosis infection were positively associated with tuberculosis infection. Tuberculosis transmission within measurable social networks may explain prevalent tuberculosis not associated with a household contact. Further study on network-informed tuberculosis case finding interventions is warranted.

Abstract Objectives: A high prevalence of prison inmates have a positive tuberculin skin test (TST) and sometimes unnecessary treatment for latent tuberculosis infection (LTBI) is prescribed. The prison tuberculosis prevention and control program has not generalized the use of QuantiFERON (QFT) in prisons. We set out to describe the implementation and usefulness of QFT in a population of inmates with positive TST, and to detect false positives and avoid unnecessary treatments. We also analysed the sociodemographic variables of the inmate population. Material and methods: All the positive TST tests between December 2020 and December 2021 from an average population of 300 inmates in Burgos prison were analysed. The QFT value was measured in all the positive cases. Sociodemographic variables were analysed and finally the number of inmates with positive TST, but with a negative QFT result and therefore not requiring LTBI treatment, was evaluated. Results: A total of 41 inmates were included in the study, with a mean age of 44 years. The proportion between Spanish inmates and foreigners was similar. Of all the positive TST, 48.8% were QFT negative. Discussion: It was observed that QFT is a safe method for the diagnosis of LTBI in prisons and that its use would contribute to a more specific selection of inmates who actually need chemoprophylactic treatment for LTBI.

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. [ABSTRACT FROM AUTHOR]

An 8-year-old girl presented with a 34-day history of cough, fatigue, and impaired exercise tolerance. She experienced cyanosis on exertion but denied fever, hemoptysis, hematuria, or seizures. Her perinatal and family histories were unremarkable, and she had no history of exposure to TB. A chest radiogram from a local clinic showed diffuse pulmonary lesions. Tuberculin skin test, interferon-γ release assay, and HIV antibody test results were all negative. Immunoglobulin levels and lymphocyte subsets were normal. The patient did not respond to IV azithromycin for 1 week for community-acquired pneumonia. She was transferred to our hospital because of progressive respiratory distress and hypoxemia. [ABSTRACT FROM AUTHOR]

Background: Tuberculides are characterised by delayed-type of immunologic reactions to Mycobacterium tuberculosis or its products in immuno-competent individuals. We herein describe clinico-epidemiological features and response to treatment in patients with tuberculides from a tertiary care centre from North India. Methods: This was a retrospective analysis of the clinical records of all the cutaneous tuberculosis (TB) patients (year 2000--2019) enrolled in the TB clinic. The patient records fulfilling the diagnostic criteria of tuberculides were considered for analysis. Results: A total of 225 patients attended the tuberculosis clinic; out of this, 34 were diagnosed as tuberculides. Out of these 34 cases, 21 were identified as LS, 2 erythema induratum of Bazin, 1 papulonecrotic tuberculide, and 10 erythema nodosum. History of contact to open cases of TB was present in 15/34 (44.1%) patients. History of BCG vaccination was found in 15/34 (44.1%) patients. The focus of underlying TB could be identified in 20/34 (58.8%) patients. Skin biopsy was performed in all patients. In all patients, the diagnosis was confirmed by clinico-pathological correlation, positive TST, and the underlying focus of TB. All patients received 6 months regimen of anti-tubercular therapy with first-line drugs. Conclusion: In this study, we demonstrated various forms of tuberculides; lichen scrofulosorum was the most common form. We also included erythema nodosum cases also, which responded well to ATT. Observation from our study showed that tuberculides are important cutaneous markers for underlying tuberculosis infection, which helps in early detection of occult tuberculosis and timely management. [ABSTRACT FROM AUTHOR]

Background Tuberculosis (TB) is an infectious disease that is still a common threat worldwide, especially in pediatric populations. TB transmission occurs particularly when the transmitter has no obvious manifestation of the disease. There is a higher incidence of TB infection in children than in the general population, especially in high risk populations such as children in orphanages. However, the incidence of TB infection in orphaned children in Indonesia, including Bali, is unknown. Objective To describe the incidence and risk factors for TB infection in children in orphanages in Bali. Methods This case-control study was conducted in 12 orphanages in Bali. Subjects were divided into a case group comprised of children with TB infection, and a control group comprised of those without TB infection. TB infection was diagnosed by positive tuberculin test without clinically confirmed TB. Results A total of 175 children were recruited as subjects. There were 49 (28.0%) children with TB infection. Bivariate analysis revealed significant associations between density, humidity, ventilation/room area ratio, and area of origin with TB infection. Multivariate analysis showed that ventilation/room area ratio and room humidity of =73% were independently positive correlated with TB infection. Natural lighting and BCG scar were not significantly different between groups. Conclusion The occurence of TB infection in children residing in orphanages in Bali is high (28%). The risk factors identified independently are lower ventilation and higher room humidity. [ABSTRACT FROM AUTHOR]

Simple Summary: This study addresses the suboptimal sensitivity of all the available ante mortem diagnostic techniques for paratuberculosis and evaluates the effect of a recent comparative intradermal tuberculin test on the humoral diagnosis of paratuberculosis in an infected caprine herd, as a potential diagnostic strategy to maximize the detection of infected animals. The results from our study showed an increase in the quantitative response detected using an ELISA technique (booster effect), which was translated into an increase, although not statistically significant, in the number of reactors. Paratuberculosis (PTB) and tuberculosis (TB) are two mycobacterial diseases with a severe economic and health impact on domestic ruminants. The ante mortem diagnosis of PTB is hampered, among other factors, by the limited sensitivity of all the available diagnostic techniques. Since TB-infected goats subjected to the comparative intradermal tuberculin test (CITT) may experience a booster effect on their antibody titer and a potential enhancement to the sensitivity of humoral techniques for tuberculosis, in the present study we aimed to evaluate this diagnostic strategy on the humoral diagnosis of PTB in serum and milk samples collected from a caprine herd that was TB free and PTB infected. The results from 120 goats indicated a significant increase (p < 0.001) in the quantitative response detected using an ELISA technique, conducted using serum and milk samples taken 15 and 30 days after performing a CITT (day 0 of the study); although, it did not translate into a significant increase in the number of reactors during any of the testing events (0, 3,15, 30 and 60 days post-CITT). Additionally, the number of ELISA-positive animals was higher for the serum versus the milk samples at both 15 and 30 days post-CITT. The increase in the quantitative ELISA result suggested a diagnostic strategy that maximizes ELISA sensitivity, mainly using serum samples, in PTB-infected herds; although, it may depend on individual differences and the interpretation criteria. [ABSTRACT FROM AUTHOR]

Caprine tuberculosis (TB) is a zoonotic disease caused by members of the Mycobacterium tuberculosis complex. TB eradication programs in goats are based on the single and comparative intradermal tuberculin tests (SITT and CITT, respectively). Antibody-based diagnostic techniques have emerged as potential diagnostic tools for TB. P22 ELISA has been previously evaluated using samples collected after the intradermal tuberculin tests to maximize the sensitivity, a phenomenon known as booster effect. However, there is no information available on whether the use of this diagnostic strategy could lead to a decrease of its specificity (Sp). The aim of the present study was to elucidate the interference effect of a recent CITT on the Sp of the P22 ELISA in serum and milk samples collected at different times after the CITT from a TB-free herd (n = 113). The number of reactors to P22 ELISA was significantly higher (p < 0.01) on serum samples collected 15 days post-CITT compared to day 0, showing a decrease in Sp from 99.1% (95% CI; 95.2-99.8%) to 88.5% (95% CI; 81.3-93.2%). The number of reactors and the quantitative values of P22 ELISA were significantly higher (p < 0.01) in serum samples compared to milk. No significant (p > 0.05) changes in the Sp of the P22 ELISA were observed throughout the different time samplings using milk No significant (p > 0.05) changes were observed on days 30 and 60 post-CITT. In conclusion, the booster effect strategy may significantly decrease the Sp of P22 ELISA in TB-free herds when serum samples are used but not when milk is tested. [ABSTRACT FROM AUTHOR]

Mycobacterium avium subspecies paratuberculosis (MAP) is a global concern in modern livestock production worldwide. The available vaccines against paratuberculosis do not offer optimal protection and interfere with the diagnosis of bovine tuberculosis. The aim of this study was to identify immunogenic MAP-specific peptides that do not interfere with the diagnosis of bovine tuberculosis. Initially, 119 peptides were selected by either (1) identifying unique MAP peptides that were predicted to bind to bovine major histocompatibility complex class II (MHC-predicted peptides) or (2) selecting hydrophobic peptides unique to MAP within proteins previously shown to be immunogenic (hydrophobic peptides). Subsequent testing of peptide-specific CD4+ T-cell lines from MAP-infected, adult goats vaccinated with peptides in cationic liposome adjuvant pointed to 23 peptides as being most immunogenic. These peptides were included in a second vaccine trial where three groups of eight healthy goat kids were vaccinated with 14 MHC-predicted peptides, nine hydrophobic peptides, or no peptides in o/w emulsion adjuvant. The majority of the MHC-predicted (93%) and hydrophobic peptides (67%) induced interferongamma (IFN-g) responses in at least one animal. Similarly, 86% of the MHCpredicted and 89% of the hydrophobic peptides induced antibody responses in at least one goat. The immunization of eight healthy heifers with all 119 peptides formulated in emulsion adjuvant identified more peptides as immunogenic, as peptide specific IFN-g and antibody responses in at least one heifer was found toward 84% and 24% of the peptides, respectively. No peptide-induced reactivity was found with commercial ELISAs for detecting antibodies against Mycobacterium bovis or MAP or when performing tuberculin skin testing for bovine tuberculosis. The vaccinated animals experienced adverse reactions at the injection site; thus, it is recommend that future studies make improvements to the vaccine formulation. In conclusion, immunogenic MAP-specific peptides that appeared promising for use in a vaccine against paratuberculosis without interfering with surveillance and trade tests for bovine tuberculosis were identified by in silico analysis and ex vivo generation of CD4+ T-cell lines and validated by the immunization of goats and cattle. Future studies should test different peptide combinations in challenge trials to determine their protective effect and identify the most MHC-promiscuous vaccine candidates. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacteria (NTM) are considered a relevant cause of non-specific reactions to the most widely applied bovine tuberculosis (bTB) test, the intradermal tuberculin test. In order to establish which NTM species might act as a potential source of such diagnostic interference, a collection of 373 isolates obtained from skin test positive cows from 359 officially tuberculosis-free (OTF) herds, culled in the framework of the bTB eradication campaign in Spain, were identified at the species level through PCR and Sanger sequencing of the 16S rDNA, hsp65 and rpoB genes.Of the 308 isolates for which a reliable identification was achieved, 32 different mycobacterial species were identified, with certain species being most represented: among M. avium complex members (n = 142, 46.1%), M. aviumsubsp. hominissuis (98; 69.0%) was themost abundant followed by M. avium subsp. avium (33, 23.2%), and M. intracellulare (7, 4.9%). Among non-MAC members (n = 166, 53.9%), M. nonchromogenicum(85; 27.6%) and M. bourgelatii (11; 5.6%) were the predominant species. In addition, mixed results were obtained in 53 isolates presenting up to 30 different genotypes, which could be indicative of new mycobacterial species. Our results represent a first step toward characterizing the diversity of NTM species that could interfere with official diagnostic tests for bTB eradication in Spain. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a serious public health concern around the world including Asia. TB burden is high in Asian countries and significant population harbor latent tuberculosis infection(LTBI). Aim: This systematic review and meta-analysis aims to evaluate the prevalence of LTBI in Asian countries. Method: We performed a systematic literature search on PubMed, Embase, and ScienceDirect to identify relevant articles published between January 1, 2005, and January 1, 2023 investigating the overall prevalence of latent TB among people of Asia. Subgroup analysis was done for Asian subregions during the study period of 2011 to 2016 and 2017 to 2023, for tuberculin skin test (TST) and interferon gamma release assay (IGRA), respectively, as well as for QuantiFERON-TB (QFT) and TSPOT TB tests. Der Simonian and Laird's random-effects model was used to pool the prevalence of LTBI found using TST and IGRA. Result: A total of 15 studies were included after a systematic search from standard electronic databases. The analysis showed that the prevalence of latent TB in Asia was 21% (95% confidence interval [CI]: 19%-23%) and 36% (95% CI: 12%-59%) according to IGRAs and TSTs (cut off 10 mm) results, respectively. Based on IGRA, the prevalence of latent TB was 20% (95% CI: 13%-25%) in 2011 to 2016 and 21% (95% CI: 18%-24%) in 2017 to 2023. Using QFT, the prevalence was 19% (95% CI: 17%-22%) and using TSPOT, the prevalence was 26% (95% CI: 21%-31%). According to the United Nations division of Asia, the prevalence was higher for the Southern region and least for the Western region using TST and higher in the South-Eastern region and least in the Western region using the IGRA test. Conclusion: Almost a quarter of the Asian population has LTBI. Its diagnosis often poses a diagnostic challenge due to the unavailability of standard test in certain areas. Given this prevalence, a mass screening program is suggested with the available standard test and public awareness along with anti-TB regimen should be considered for individuals who test positive. However, for it to be implemented effectively, we need to take the affordability, availability, and cost-effectiveness of such interventions into account. [ABSTRACT FROM AUTHOR]

In this review, the infectious complications observed in sarcoidosis are considered from a practical point of view to help the clinician not to overlook them in a difficult context, as pulmonary sarcoidosis makes the recognition of superinfections more difficult. An increased incidence of community-acquired pneumonia and of opportunistic pneumonia has been reported, especially in immunosuppressed patients. Pulmonary destructive lesions of advanced sarcoidosis increase the incidence of chronic pulmonary aspergillosis and infection by other agents. Screening and treatment of latent tuberculosis infection are crucial to prevent severe tuberculosis. Severity in COVID-19 appears to be increased by comorbidities rather than by sarcoidosis per se. The diagnosis of infectious complications can be challenging and should be considered as a potential differential diagnosis when the exacerbation of sarcoidosis is suspected. These complications not only increase the need for hospitalizations, but also increase the risk of death. This aspect must be carefully considered when assessing the overall health burden associated with sarcoidosis. The impact of immune dysregulation on infectious risk is unclear except in exceptional cases. In the absence of evidence-based studies on immunosuppressants in the specific context of pulmonary sarcoidosis, it is recommended to apply guidelines used in areas outside sarcoidosis. Preventive measures are essential, beginning with an appropriate use of immunosuppressants and the avoidance of unjustified treatments and doses. This approach should take into account the risk of tuberculosis, especially in highly endemic countries. Additionally, parallel emphasis should be placed on vaccinations, especially against COVID-19. [ABSTRACT FROM AUTHOR]

Background Tuberculosis (TB) disease has been associated with pregnancy complications. However, the potential impact of TB infection (TBI) on pregnancy outcome is unknown. To investigate this, we conducted a register-based study in immigrant women screened with QuantiFERON assays for TBI in antenatal care in Sweden. Methods Women with history of immigration from TB-endemic countries were eligible for inclusion if national identification numbers and available QuantiFERON results obtained during pregnancy from 2014 to 2018 were available. QuantiFERON results were linked to data on maternal characteristics and pregnancy outcomes from the national Pregnancy and Patient Registers. TBI was defined as nil-corrected QuantiFERON result ≥0.35 IU/mL, in the absence of TB disease. Pregnancies in women with TB disease or human immunodeficiency virus were excluded, as were multiplex pregnancies, pregnancies resulting in miscarriage, and pregnancies occurring >10 years after immigration. Odds of defined adverse pregnancy outcomes were compared by maternal TBI status using mixed effects logistic regression with adjustment for maternal age and region of origin. Results In total, 7408 women with 12 443 pregnancies were included. In multivariable analysis, stillbirth (adjusted odds ratio [AOR], 1.90; 95% confidence interval [CI], 1.13–3.21; P =.016), severe preeclampsia (AOR, 1.62; 95% CI, 1.03–2.56; P =.036), low birthweight (<2500 g; AOR, 1.38; 95% CI, 1.01–1.88; P =.041), and emergency cesarean section (AOR, 1.28; 95% CI, 1.02–1.63; P =.033) were significantly associated with TBI. Conclusions Among immigrant women seeking antenatal care in Sweden, TBI was independently associated with adverse pregnancy outcomes. Further studies are needed to corroborate these findings and to explore mechanisms involved. [ABSTRACT FROM AUTHOR]

Study design: Systematic review. Introduction: Total hip arthroplasty (THA) is a well-acknowledged surgical intervention to restore a painless and mobile joint in patients with osteoarticular tubercular arthritis of the hip joint. However, there is still substantial uncertainty about the ideal management, clinical and functional outcomes following THA undertaken in patients with acute Mycobacterium tuberculosis (TB) hip infections. Aim of the study: To undertake a systematic review and evaluate existing literature on patients undergoing THA for acute mycobacterium tuberculosis arthritis of the hip. Methods: A systematic review of electronic databases of PubMed, EMBASE, Scopus, Web of Science and Cochrane Library was performed on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search focused on "arthroplasty in cases with tuberculosis of hip joint" since inception of databases until July 2023. Data on patient demographics, clinical characteristics, treatment administered, surgical interventions and outcome, as reported in the included studies, were recorded. Median (range) and mean (standard deviation) were used to summarise the data for continuous variables (as reported in the original studies); and frequency/percentage was employed for categorical variables. Available data on Harris hip scores and complications were statistically pooled using random-effects meta-analysis or fixed-effect meta-analysis, as appropriate Results: Among a total of 1695 articles, 15 papers were selected for qualitative summarisation and 12 reporting relevant data were included for proportional meta-analysis. A total of 303 patients (mean age: 34 to 52 years; mean follow-up: 2.5 to 10.5 years) were included in our systematic review. In a majority of included studies, postero-lateral approach and non-cemented prosthesis were employed. Fourteen studies described a single-staged procedure in the absence of sinus, abscess and tubercular infection syndrome (TIS). All surgeries were performed under cover of prolonged course of multi-drug anti-tubercular regimen. The mean Harris hip score (HHS) at final follow-up was 91.36 [95% confidence interval (CI): 89.56–93.16; I2:90.44%; p<0.001]. There were 30 complications amongst 174 (9.9%) patients (95% CI: 0.06–0.13; p=0.14; I2=0%). Conclusion: THA is a safe and effective surgical intervention in patients with active and advanced TB arthritis of hip. It is recommended that the surgery be performed under cover of multi-drug anti-tubercular regimen. In patients with active sinus tracts, abscesses and TIS, surgery may be accomplished in a multi-staged manner. The clinical (range of motion, deformity correction, walking ability and pain scores), radiological (evidence of radiological reactivation and implant incorporation) and function outcome (as assessed by HHS) significantly improve after THA in these patients. [ABSTRACT FROM AUTHOR]

Double antibody positive renal vasculitis (anti GBM antibody and pANCA) is a rare form of small vessel vasculitis associated with poor outcome. It is difficult to decide which antibody is the precursor in these cases. We report here such a rare case of double antibody positive renal vasculitis which was started on anti tubercular medicine for a positive mantoux test and interferon gamma release assay. The possible reasons for these antibodies in this may be a complication of COVID-19 infection or vaccine, adverse drug effect of antitubercular medicines or a paradoxical reaction during the tuberculosis treatment. The patient could not survive beyond two months of diagnosis because of rapidly declining renal functions. This case highlights the importance of a meticulous clinical approach, supports two week tuberculosis medicines trial and an early and careful dealing of non responders during tuberculosis treatment especially in patients whose diagnosis is not microbiologically confirmed. [ABSTRACT FROM AUTHOR]