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Abstract Background Most new cases of active tuberculosis in Norway are presently caused by imported strains and not transmission within the country. Screening for tuberculosis with a Mantoux test of everybody and a chest X-ray of those above 15 years of age is compulsory on arrival for asylum seekers. We aimed to assess the effectiveness of entry screening of a cohort of asylum seekers. Cases detected by screening were compared with cases detected later. Further we have characterized cases with active tuberculosis. Methods All asylum seekers who arrived at the National Reception Centre between January 2005 - June 2006 with an abnormal chest X-ray or a Mantoux test ≥ 6 mm were included in the study and followed through the health care system. They were matched with the National Tuberculosis Register by the end of May 2008. Cases reported within two months after arrival were defined as being detected by screening. Results Of 4643 eligible asylum seekers, 2237 were included in the study. Altogether 2077 persons had a Mantoux ≥ 6 mm and 314 had an abnormal chest X-ray. Of 28 cases with tuberculosis, 15 were detected by screening, and 13 at 4-27 months after arrival. Abnormal X-rays on arrival were more prevalent among those detected by screening. Female gender and Somalian origin increased the risk for active TB. Conclusion In spite of an imperfect follow-up of screening results, a reasonable number of TB cases was identified by the programme, with a predominance of pulmonary TB.

Abstract Background About 80% of new tuberculosis cases in Norway occur among immigrants from high incidence countries. On arrival to the country all asylum seekers are screened with Mantoux test and chest x-ray aimed to identify cases of active tuberculosis and, in the case of latent tuberculosis, to offer follow-up or prophylactic treatment. We assessed a national programme for screening, treatment and follow-up of tuberculosis infection and disease in a cohort of asylum seekers. Methods Asylum seekers ≥ 18 years who arrived at the National Reception Centre from January 2005 to June 2006, were included as the total cohort. Those with a Mantoux test ≥ 6 mm or positive x-ray findings were included in a study group for follow-up. Data were collected from public health authorities in the municipality to where the asylum seekers had moved, and from hospital based internists in case they had been referred to specialist care. Individual subjects included in the study group were matched with the Norwegian National Tuberculosis Register which receive reports of everybody diagnosed with active tuberculosis, or who had started treatment for latent tuberculosis. Results The total cohort included 4643 adult asylum seekers and 97.5% had a valid Mantoux test. At least one inclusion criterion was fulfilled by 2237 persons. By end 2007 municipal public health authorities had assessed 758 (34%) of them. Altogether 328 persons had been seen by an internist. Of 314 individuals with positive x-rays, 194 (62%) had seen an internist, while 86 of 568 with Mantoux ≥ 15, but negative x-rays (16%) were also seen by an internist. By December 31st 2006, 23 patients were diagnosed with tuberculosis (prevalence 1028/100 000) and another 11 were treated for latent infection. Conclusion The coverage of screening was satisfactory, but fewer subjects than could have been expected from the national guidelines were followed up in the community and referred to an internist. To improve follow-up of screening results, a simplification of organisation and guidelines, introduction of quality assurance systems, and better coordination between authorities and between different levels of health care are all required.

Abstract Background In Norway, screening for tuberculosis infection by tuberculin skin test (TST) has been offered for several decades to all children in 9th grade of school, prior to BCG-vaccination. The incidence of tuberculosis in Norway is low and infection with M. tuberculosis is considered rare. QuantiFERON®TB Gold (QFT) is a new and specific blood test for tuberculosis infection. So far, there have been few reports of QFT used in screening of predominantly unexposed, healthy, TST-positive children, including first and second generation immigrants. In order to evaluate the current TST screening and BCG-vaccination programme we aimed to (1) measure the prevalence of QFT positivity among TST positive children identified in the school based screening, and (2) measure the association between demographic and clinical risk factors for tuberculosis infection and QFT positivity. Methods This cross-sectional multi-centre study was conducted during the school year 2005–6 and the TST positive children were recruited from seven public hospitals covering rural and urban areas in Norway. Participation included a QFT test and a questionnaire regarding demographic and clinical risk factors for latent infection. All positive QFT results were confirmed by re-analysis of the same plasma sample. If the confirmatory test was negative the result was reported as non-conclusive and the participant was offered a new test. Results Among 511 TST positive children only 9% (44) had a confirmed positive QFT result. QFT positivity was associated with larger TST induration, origin outside Western countries and known exposure to tuberculosis. Most children (79%) had TST reactions in the range of 6–14 mm; 5% of these were QFT positive. Discrepant results between the tests were common even for TST reactions above 15 mm, as only 22 % had a positive QFT. Conclusion The results support the assumption that factors other than tuberculosis infection are widely contributing to positive TST results in this group and indicate the improved specificity of QFT for latent tuberculosis. Our study suggests a very low prevalence of latent tuberculosis infection among 9th grade school children in Norway. The result will inform the discussion in Norway of the usefulness of the current TST screening and BCG-policy.

Abstract Background QuantiFERON®TB Gold (QFT) is a promising blood test for tuberculosis infection but with few data so far from immigrant screening. The aim of this study was to compare results of QFT and tuberculin skin test (TST) among newly arrived asylum seekers in Norway and to assess the role of QFT in routine diagnostic screening for latent tuberculosis infection. Methods The 1000 asylum seekers (age ≥ 18 years) enrolled in the study were voluntarily recruited from 2813 consecutive asylum seekers arriving at the national reception centre from September 2005 to June 2006. Participation included a QFT test and a questionnaire in addition to the mandatory TST and chest X-ray. Results Among 912 asylum seekers with valid test results, 29% (264) had a positive QFT test whereas 50% (460) tested positive with TST (indurations ≥ 6 mm), indicating a high proportion of latent infection within this group. Among the TST positive participants 50% were QFT negative, whereas 7% of the TST negative participants were QFT positive. There was a significant association between increase in size of TST result and the likelihood of being QFT positive. Agreement between the tests was 71–79% depending on the chosen TST cut-off and it was higher for non-vaccinated individuals. Conclusion By using QFT in routine screening, further follow-up could be avoided in 43% of the asylum seekers who would have been referred if based only on a positive TST (≥ 6 mm). The proportion of individuals referred will be the same whether QFT replaces TST or is used as a supplement to confirm a positive TST, but the number tested will vary greatly. All three screening approaches would identify the same proportion (88–89%) of asylum seekers with a positive QFT and/or a TST ≥ 15 mm, but different groups will be missed.

Abstract Background Delay in start of tuberculosis (TB) treatment has an impact at both the individual level, by increasing the risk of morbidity and mortality, and at the community level, by increasing the risk of transmission. The aims of this study were to assess the delays in the start of treatment for TB patients in Oslo/Akershus region, Norway and to analyze risk factors for the delays. Methods This study was based on information from the National TB Registry, clinical case notes from hospitals and referral case notes from primary health care providers. Delays were divided into patient, health care system and total delays. The association with sex, birthplace, site of the disease and age group was analyzed by multiple linear regression. Results Among the 83 TB patients included in this study, 71 (86%) were born abroad. The median patient, health care system and total delays were 28, 33 and 63 days respectively, with a range of 1–434 days. In unadjusted analysis, patient delay and health care system delay did not vary significantly between men and women, according to birthplace or age group. Patients with extra-pulmonary TB had a significantly longer patient, health care system and total delay compared to patients with pulmonary TB. Median total delay was 81 and 56 days in the two groups of TB patients respectively. The health care system delay exceeded the patient delay for those born in Norway. The age group 60+ years had significantly shorter patient delay than the reference group aged 15–29 years when adjusted for multiple covariates. Also, in the multivariate analysis patients born in Norway had significantly longer health care system delay than patients born abroad. Conclusion A high proportion of patients had total delays in start of TB treatment exceeding two months. This study emphasizes the need of awareness of TB in the general population and among health personnel. Extra-pulmonary TB should be considered as a differential diagnosis in unresolved cases, especially for immigrants from high TB prevalence countries.

Abstract Background The key elements in tuberculosis (TB) control are to cure the individual patient, interrupt transmission of TB to others and prevent the tubercle bacilli from becoming drug resistant. Incomplete treatment may result in excretion of bacteria that may also acquire drug resistance and cause increased morbidity and mortality. Treatment outcome results serves as a tool to control the quality of TB treatment provided by the health care system. The aims of this study were to evaluate the treatment outcome for new cases of culture positive pulmonary TB registered in Norway during the period 1996–2002 and to identify factors associated with non-successful treatment. Methods This was a register-based cohort study. Treatment outcome was assessed according to sex, birthplace, age group, isoniazid (INH) susceptibility, mode of detection and treatment periods (1996–1997, 1998–1999 and 2000–2002). Logistic regression was also used to estimate the odds ratio for treatment success vs. non-success with 95% confidence interval (CI), taking the above variables into account. Results Among the 655 patients included, the total treatment success rate was 83% (95% CI 80%–86%). The success rates for those born in Norway and abroad were 79% (95% CI 74%–84%) and 86% (95% CI 83%–89%) respectively. There was no difference in success rates by sex and treatment periods. Twenty-two patients (3%) defaulted treatment, 58 (9%) died and 26 (4%) transferred out. The default rate was higher among foreign-born and male patients, whereas almost all who died were born in Norway. The majority of the transferred out group left the country, but seven were expelled from the country. In the multivariate analysis, only high age and initial INH resistance remained as significant risk factors for non-successful treatment. Conclusion Although the TB treatment success rate in Norway has increased compared to previous studies and although it has reached a reasonable target for treatment outcome in low-incidence countries, the total success rate for 1996–2002 was still slightly below the WHO target of success rate of 85%. Early diagnosis of TB in elderly patients to reduce the death rate, abstaining from expulsion of patients on treatment and further measures to prevent default could improve the success rate further.

Background: QuantiFERONTB Gold (QFT) is a promising blood test for tuberculosis infection but with few data so far from immigrant screening. The aim of this study was to compare results of QFT and tuberculin skin test (TST) among newly arrived asylum seekers in Norway and to assess the role of QFT in routine diagnostic screening for latent tuberculosis infection.Methods: The 1000 asylum seekers (age > or = 18 years) enrolled in the study were voluntarily recruited from 2813 consecutive asylum seekers arriving at the national reception centre from September 2005 to June 2006. Participation included a QFT test and a questionnaire in addition to the mandatory TST and chest X-ray.Results: Among 912 asylum seekers with valid test results, 29% (264) had a positive QFT test whereas 50% (460) tested positive with TST (indurations > or = 6 mm), indicating a high proportion of latent infection within this group. Among the TST positive participants 50% were QFT negative, whereas 7% of the TST negative participants were QFT positive. There was a significant association between increase in size of TST result and the likelihood of being QFT positive. Agreement between the tests was 71-79% depending on the chosen TST cut-off and it was higher for non-vaccinated individuals.Conclusion: By using QFT in routine screening, further follow-up could be avoided in 43% of the asylum seekers who would have been referred if based only on a positive TST (> or = 6 mm). The proportion of individuals referred will be the same whether QFT replaces TST or is used as a supplement to confirm a positive TST, but the number tested will vary greatly. All three screening approaches would identify the same proportion (88-89%) of asylum seekers with a positive QFT and/or a TST > or = 15 mm, but different groups will be missed. [ABSTRACT FROM AUTHOR]

Background: In Pakistan, 84% of healthcare is provided by the private sector. We conducted an epidemiological and programme review for TB to document progress and guide further efforts., Methods: Surveillance and data systems were assessed before analysing epidemiological data. We reviewed the programme at federal, provincial and peripheral levels and compiled national data along with WHO estimates to describe the evolution of epidemiological and programme indicators., Results: In 2021, of the estimated number of TB cases, 55% of overall cases and 18% of drug-resistant cases were diagnosed and treated respectively. The contribution of the private sector in case detection increased from 30% in 2017 to 40% by 2021. For newly diagnosed pulmonary TB cases, the overall proportion of confirmed cases was 52%. In 2021, testing for rifampicin resistance among confirmed cases was 66% for new and 84% for previously treated patients. The treatment success rate exceeded 90% for drug susceptible TB. The main challenges identified were a funding gap (60% in 2021-2023), fragmented electronic systems for data collection and suboptimal coordination among provinces., Conclusions: The main challenges prevent further progress in controlling TB. By addressing these, Pakistan could improve coverage of interventions, including diagnosis and treatment. Bacteriological confirmation using recommended diagnostics also requires further optimisation., Competing Interests: Conflicts of interest: none declared., (© 2024 The Authors.)

Background: T cell infiltration around dying motor neurons is a hallmark of amyotrophic lateral sclerosis (ALS). It is not known if this immune response represents a cause or a consequence of the disease. We aimed to establish whether individual variation in regulation of a T cell driven immune response is associated with long-term ALS risk., Methods: Tuberculin skin test (TST) following BCG vaccination represents a standardized measure of a secondary T cell driven immune response. During a Norwegian tuberculosis screening program (1963-1975) Norwegian citizens born from 1910 to 1955 underwent TST. In those previously BCG vaccinated (median 7 years prior to TST), we related tuberculin skin tests to later ALS disease identified through validated Norwegian health registers. We fitted Cox proportional hazard models to investigate the association between tuberculin reactivity and ALS risk., Results: Among 324,629 participants (52 % women) with median age 22 (IQR 10) years at tuberculosis screening, 496 (50 % women) later developed ALS. Hazard ratio for ALS was 0.74 (95% CI 0.57-0.95) for those who remained TST negative compared to those who mounted a positive TST. The association was strongest when time between BCG immunization and TST was short. The associations observed persisted for more than four decades after TST measurement., Conclusions: Negative TST responses after BCG vaccination is associated with decreased long-term risk for ALS development, supporting a primary role for adaptive immunity in ALS development., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: In Ethiopia, one-third of the estimated tuberculosis cases are not detected or reported. Incidence estimates are inaccurate and rarely measured directly. Assessing the 'real' incidence under programme conditions is useful to understand the situation. This study aimed to measure the prevalence and incidence of symptomatic pulmonary tuberculosis (PTB) during 1 year in the adult population of Dale in Ethiopia., Design: A prospective population-based cohort study., Setting: Every household in Dale was visited three times at 4-month intervals., Participants: Individuals aged ≥15 years., Outcome Measures: Microscopy smear positive PTB (PTB s+), bacteriologically confirmed PTB (PTB b+) by microscopy, GeneXpert, or culture and clinically diagnosed PTB (PTB c+)., Results: Among 136 181 individuals, 2052 had presumptive TB (persistent cough for 14 days or more with or without haemoptysis, weight loss, fever, night sweats, chest pain or difficulty breathing ), in the first round of household visits including 93 with PTB s+, 98 with PTB b+ and 24 with PTB c+; adding those with PTB who were already on treatment, the total number of PTB was 201, and the prevalence was 147 (95% CI: 127 to 168)/100 000 population. Out of all patients with PTB, the proportion detected by symptom screening was in PTB s+ 65%, PTB b+ 67% and PTB c+44%. During 96 388 person-years follow-up, 1909 had presumptive TB, 320 had PTB and the total incidence of PTB was 332 (95% CI: 297 to 370)/100 000 person-years, while the incidence of PTB s+, PTB b+ and PTB c+ was 230 (95% CI: 201 to 262), 263 (95% CI: 232 to 297) and 68 (95% CI: 53 to 86)/100 000 person-years, respectively., Conclusion: The prevalence of symptomatic sputum smear-positive TB was still high, only one-third of prevalent PTB cases notified and the incidence rate highest in the age group 25-34 years, indicating ongoing transmission. Finding missing people with TB through repeated symptom screening can contribute to reducing transmission., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The World Health Organization guidelines for management drug resistant tuberculosis include surgery as an additional method in selected cases. Pneumonectomies have higher risk of morbidity such as bronchial fistulas which may be prevented by bronchial stump covering. We compare two methods of bronchial stump reinforcement., Methods and Materials: A retrospective single center follow-up study was done in 52 patients who underwent pneumonectomy for drug resistant pulmonary tuberculosis. Between 2000 and 2017 we performed pneumonectomies with pericardial fat reinforcement of bronchial stump in group 1 ( n  = 42), and between 2017 and 2021 in group 2 with pedicled muscle flap reinforcement group 2 ( n  = 10)., Results: Bronchial fistulas occurred in 17/42 (41%) of patients group 1 and there was no fistula in group 2, and this was statistically different (Fisher's test p  = 0.02). Post-operative complications were seen in 24/42 (57%) of the patients in Group 1, and 4/10 (40%) patients in Group 2 (Fischer's test p  = 0.53). In group 1 positive bacteriology decreased from 74% to 24% just after surgery, and in group 2 it decreased from 90% to 10%, but this was not statistically different (Fisher's test p  = 0.63). In group 1 no-one died the first month, but 8/42 (19%) died within a year; in group 2 one died within a month, and only this death (10%) within a year. This difference in case fatality was not statistically significant., Conclusions: The use of pedicle muscle flap for bronchial stump coverage during the pneumonectomies for destructive drug resistant tuberculosis can prevent severe postoperative fistulas and improve postoperative life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bazhenov, Mariandyshev, Hinderaker, Heldal, Motus, Vasilyeva.)

Background: Multiple sclerosis (MS) is characterized by inflammatory lesions in the central nervous system involving pro-inflammatory T-cells. Immune dysregulation is well described in prevalent disease, but it is not known whether this precedes disease development. Bacillus Calmette-Guérin (BCG) vaccination ameliorates MS-like disease in mice. In people vaccinated with BCG, the tuberculin skin test (TST) offers a standardized measure of a T-cell-mediated immune response. We therefore hypothesized that the strength of the TST response after BCG vaccination is associated with subsequent MS risk., Methods: Using data from a Norwegian tuberculosis screening programme (1963-1975), we designed a population-based cohort study and related the size of TST reactions in individuals previously vaccinated with BCG to later MS disease identified through the Norwegian MS registry. We fitted Cox proportional hazard models and flexible parametric survival models to investigate the association between TST reactivity, MS risk and its temporal relationship., Results: Among 279 891 participants (52% females), 679 (69% females) later developed MS. Larger TST reactivity was associated with decreased MS risk. The hazard ratio for MS per every 4-mm increase in skin induration size was 0.86 (95% confidence interval 0.76-0.96) and similar between sexes. The strength of the association persisted for >30 years after the TST., Conclusion: A strong in vivo vaccine response to BCG is associated with reduced MS risk >30 years later. The immunological mechanisms determining TST reactivity suggest that skewed T-cell-mediated immunity precedes MS onset by many decades., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objective: Many individuals with persistent cough and smear microscopy-negative sputum test for tuberculosis (TB) remain at risk of developing the disease. This study estimates the incidence of pulmonary TB (PTB) among initially smear-negative persistent coughers and its risk factors., Design: A prospective population-based follow-up study., Setting: Health extension workers visited all households in Dale woreda three times at 4-month intervals in 2016-2017 to identify individuals with symptoms compatible with TB (presumptive TB) using pretested and semistructured questionnaires., Participants: We followed 3484 presumptive TB cases (≥15 years) with an initial smear-negative TB (PTB) test., Outcome Measures: Bacteriologically confirmed PTB (PTB b+) and clinically diagnosed PTB (PTB c+)., Results: 3484 persons with initially smear-negative presumptive PTB were followed for 2155 person-years (median 0.8 years); 90 individuals had PTB b+ and 90 had PTB c+. The incidence rates for PTB b+ and PTB c+ were both 4176 (95% CI 3378 to 5109) per 100 000 person-years. We used penalised (lasso) and non-penalised proportional hazards Cox regression models containing all exposures and outcomes to explore associations between exposures and outcomes. In lasso regression, the risk of development of PTB b+ was 63% (HR 0.37) lower for people aged 35-64 years and 77% (HR 0.23) lower for those aged ≥65 years compared with 15-34 year-olds. Men had a 62% (HR 1.62) greater risk of PTB b+ development than women. The risk of PTB c+ was 39% (HR 0.61) lower for people aged 35-54 years than for those aged 15-34 years. Men had a 56% (HR 1.56) greater risk of PTB c+ development than women., Conclusions: PTB incidence rate among persistent coughers was high, especially among men and young adults, the latter signifying sustained transmission. Awareness about this among healthcare workers may improve identification of more new TB cases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pakistan implemented initiatives to detect tuberculosis (TB) patients through extended contact screening (ECS); it improved case detection but treatment outcomes need assessment., Objectives: To compare treatment outcomes of pulmonary TB (PTB) patients detected by ECS with those detected by routine passive case finding (PCF)., Methods: A cohort study using secondary program data conducted in Lahore, Faisalabad and Rawalpindi districts and Islamabad in 2013-15. We used log binomial regression models to assess if ECS was associated with unfavorable treatment outcomes (death, loss-to-follow-up, failure, not evaluated) after adjusting for potential confounders., Results: We included 79,431 people with PTB; 4604 (5.8%) were detected by ECS with 4052 (88%) bacteriologically confirmed. In all PTB patients the proportion with unfavorable outcomes was not significantly different in ECS group (9.6%) compared to PCF (9.9%), however, among bacteriologically confirmed patients unfavorable outcomes were significantly lower in ECS (9.9%) than PCF group (11.6%, P = 0.001). ECS was associated with a lower risk of unfavorable outcomes (adjusted relative risk (aRR) 0.90; 95% CI 0.82-0.99) among 'all PTB' patients and bacteriologically confirmed PTB patients (aRR 0.91; 95% CI 0.82-1.00)., Conclusion: In PTB patients detected by ECS the treatment outcomes were not inferior to those detected by PCF., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Immune-mediated bone loss significantly impacts fracture risk in patients with autoimmune disease, but to what extent individual variations in immune responses affect fracture risk on a population level is unknown. To examine how immune responses relate to risk of hip fracture, we looked at the individual variation in a post-vaccination skin test response that involves some of the immune pathways that also drive bone loss. From 1963 to 1975, the vast majority of the Norwegian adult population was examined as part of the compulsory nationwide Norwegian mass tuberculosis screening. These examinations included standardized tuberculin skin tests (TSTs). Our study population included young individuals (born 1940 to 1960 and aged 14 to 30 years at examination) who had all received Bacille Calmette-Guerin (BCG) vaccination after a negative TST at least 1 year prior and had no signs of tuberculosis upon clinical examination. The study population ultimately included 244,607 individuals, whose data were linked with a national database of all hospitalized hip fractures in Norway from 1994 to 2013. There were 3517 incident hip fractures during follow-up. Using a predefined Cox model, we found that men with a positive or a strong positive TST result had a 20% (hazard ratio [HR] = 1.20, 95% confidence interval [CI] 1.01-1.44) and 24% (HR = 1.24, 95% CI 1.03-1.49) increased risk of hip fracture, respectively, compared with men with a negative TST. This association was strengthened in sensitivity analyses. Total hip bone mineral density (BMD) was available for a limited subsample and similarly revealed a non-significantly reduced BMD among men with a positive TST. Interestingly, no such clear association was observed in women. An increased immune response after vaccination is associated with an increased risk of hip fracture decades later among men, possibly because of increased immune-mediated bone loss. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)