Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018.

BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.

Immunogenicity of SARS-CoV-2 mRNA vaccine in solid organ transplant recipients.

BACKGROUND: It is currently not well described if a two-dose regimen of a Covid-19 vaccine is sufficient to elicit an immune response in solid organ transplant (SOT) recipients. RESULTS: A total of 80 SOT recipients completed a two-dose regimen with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA vaccine. Only 35.0% (n = 28) were able to mount a positive IgG immune response 6 weeks after the second dose of vaccine. CONCLUSION: This emphasizes that SOT recipients need continued use of personal protective measures. Future studies need to closely examine the cellular immune response in patients with compromised antibody response to Covid-19 vaccination.

Underreporting of patients diagnosed with tuberculosis in the Region of Southern Denmark.

Background: Tuberculosis (TB) is a notifiable disease in Denmark. Underreporting leads to underestimation of the disease burden and may impede disease control. To date, no other published studies have examined underreporting of TB in the Danish setting. Method: Records of patients in the Region of Southern Denmark diagnosed with TB from 2009 to 2014 in the Danish National Patient Registry (DNPR) were linked to the national notification database. Medical records of non-notified patients were reviewed, followed by statistical comparison of demographic and medical parameters with notified TB patients in the region. Results: In the study period, 28.9% (n=30) of clinically diagnosed, culture-negative TB cases were not notified, corresponding to an overall TB underreporting rate of 7.5%. Non-notified patients had fewer co-morbidities and were less likely to have had previous TB episodes. Incidentally, we found a high number (71.1%) of erroneous TB diagnoses in the DNPR. Conclusions: Accurate data based on notification is essential to understand possible needs for preventive actions in the population. Our study demonstrates the existence of underreporting of culture-negative TB cases in the Region of Southern Denmark.

Review of tuberculosis treatment outcome reporting system in Denmark, a retrospective study cohort study from 2009 through 2014.

BACKGROUND: In Denmark, reporting of tuberculosis (TB) treatment outcome is voluntary and data incomplete. In the European Centre for Disease Prevention and Control most recent report presenting data from 2017, only 53.9% of Danish pulmonary TB cases had a reported outcome. Monitoring of TB treatment outcome is not feasible based on such limited results. In this retrospective study from 2009 to 2014, we present complete treatment outcome data and describe characteristics of cases lost to follow up. METHODS: All cases notified from 2009 through 2014 were reviewed. Hospital records were examined, and TB treatment outcome was categorized according to the World Health Organization's (WHO) definitions. RESULTS: A total of 2131 TB cases were included. Treatment outcome was reported to the Surveillance Unit in 1803 (84.6%) cases, of which 468 (26.0%) were reclassified. For pulmonary TB, 339 (28.9%) cases were reclassified between cured and treatment completed. Overall, the proportion of cases who achieved successful treatment outcome increased from 1488 (70.4%) to 1748 (81.8%). CONCLUSION: A high number of cases were reclassified during the review process. Increased focus on correct treatment outcome reporting is necessary in Denmark. A more comprehensive and exhaustive categorization of TB treatment outcome could be beneficial, especially for cases where collection of sputum or tissue towards the end of treatment is challenging.

The epidemiology of bacille Calmette-Guérin infections after bladder instillation from 2002 through 2017: a nationwide retrospective cohort study.

OBJECTIVE: To describe incidence and clinical characteristics of bacille Calmette-Guérin (BCG) infections after BCG bladder instillation amongst patients with non-muscle-invasive bladder cancer in Denmark. PATIENTS AND METHODS: We conducted a nationwide register-based cohort study in Denmark between 2002 through 2017. Patients with BCG infection were identified by cross-linking data from the Danish National Hospital Registry on patients treated with BCG instillations and patients diagnosed with tuberculosis according to the International Classification of Diseases 10, and data obtained from International Reference Laboratory of Mycobacteriology. Hospital records were reviewed for clinical information. RESULTS: During the study period, 6753 patients (5281 men; mean [SD] age 71.1 (0.1) years) received BCG instillations, of which 66 patients (1%) developed BCG infections. There were no differences in age or Charlson Comorbidity Index between the patients in the study population stratified by BCG infection. The median (interquartile range) time from first BCG instillation until symptoms of BCG infection was 169.5 (38-585) days. Extrapulmonary localisation of BCG infections (37 patients, 56.1%) was significantly more frequent than pulmonary BCG infections (20 patients, 30.3%; P < 0.001). The most common extrapulmonary localisation was the genitourinary tract (29 patients, 78.4%). CONCLUSION: BCG infections after bladder instillation are rare, mainly affect male patients, and are most frequently extrapulmonary. BCG infections should be suspected despite a long time span between occurrence of symptoms and prior bladder instillation.

Humoral immune response following a third SARS-CoV-2 mRNA vaccine dose in solid organ transplant recipients compared with matched controls.

Background: Solid organ transplant (SOT) recipients have shown suboptimal antibody response following COVID-19 vaccination. Several risk factors for the diminished response have been identified including immunosuppression and older age, but the influence of different comorbidities is not fully elucidated. Method: This case-control study consisted of 420 Danish adult SOT recipients and 840 sex- and age-matched controls, all vaccinated with a third homologous dose of either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. The primary outcome was differences in humoral immune response. The secondary outcome was breakthrough infections. Additionally, we looked for factors that could predict possible differences between the two groups. Results: Response rate increased from 186/382 (49%) to 275/358 (77%) in SOT recipients and remained on 781/790 (99%) to 601/609 (99%) in controls following a third vaccine dose. SOT recipients had significantly lower median antibody concentrations after third dose compared to controls (332.6 BAU/ml vs 46,470.0 BAU/ml, p <0.001). Lowest median antibody concentrations were seen in SOT recipients with liver disease (10.3 BAU/ml, IQR 7.1-319) and diabetes (275.3 BAU/ml, IQR 7.3-957.4). Breakthrough infections occurred similarly frequent, 150 (40%) among cases and 301 (39%) among controls (p = 0.80). Conclusion: A third COVID-19 vaccine dose resulted in a significant increase in humoral immunogenicity in SOT recipients and maintained high response rate in controls. Furthermore, SOT recipients were less likely to produce antibodies with overall lower antibody concentrations and humoral immunity was highly influenced by the presence of liver disease and diabetes. The prevalence of breakthrough infections was similar in the two groups.

Characteristics and predictors for tuberculosis related mortality in Denmark from 2009 through 2014: A retrospective cohort study.

OBJECTIVES: Mortality from tuberculosis (TB) has been declining since 2000, nevertheless there is still a significant number of patients who die before or during TB treatment. The aims were to examine and describe predictors associated with TB related mortality. METHODS: Patients notified with TB from 2009 though 2014 in Denmark were included. Data were extracted from national registers and patient records were examined for clinical information and treatment outcome. Cox proportional hazards regression was used to examine TB related mortality. RESULTS: A total of 2131 cases were identified, 141 (6.6%) patients died before or during TB treatment. TB related mortality accounted for 104 cases (73.8%) and decreased significantly from 6.7% to 3.2% (p = .04) during the study period. Within 1 months of diagnosis, 49% of TB related deaths had occurred. The strongest risk factors present at time of diagnosis, associated with TB related mortality, were: age > 70 years, Charlson comorbidity index > 1, alcohol abuse, weight loss, anemia, and C-reactive protein > 100 mg/L (p < .05). CONCLUSION: The majority of TB related deaths occurred soon after diagnosis, emphasizing that TB patients identified to have a high risk of mortality should be closely monitored before and during the intensive treatment period to improve their outcomes.

Predictors for Pulmonary Tuberculosis Treatment Outcome in Denmark 2009-2014.

Monitoring of tuberculosis (TB) treatment outcome is essential to ensure an effective TB control program. In this nationwide retrospective cohort study from Denmark we present TB treatment outcome rates and risk factors associated with an unfavourable outcome. All patients notified with pulmonary TB from 2009 through 2014 were included. Logistic regression analyses were used to identify risk factors for unfavourable outcome. In total, 1681 pulmonary TB cases were included. TB treatment success rates increased during the study period. In 2014, the treatment success rate reached 85% for new culture positive cases whereas 7% cases interrupted treatment. The mortality decreased during the study period from 12.3% to 4.1%. Several risk factors associated with unfavourable outcome were identified in a multivariable model: male (OR: 2.56), Greenlandic origin (OR: 1.80), abuse of alcohol (OR: 2.90), history of mental disorder (OR: 2.46), and anaemia at time of treatment initiation (OR: 1.92). In a TB low incidence setting such as the Danish, it is important to maintain focus on preventing an unfavourable TB outcome. Patient management and treatment can be optimized by taking into consideration risk factors such as those identified in the present study.

Extrapulmonary Tuberculosis in Denmark From 2009 to 2014; Characteristics and Predictors for Treatment Outcome.

BACKGROUND: Extrapulmonary tuberculosis (EPTB) represents an increasing percentage of tuberculosis (TB) cases in Europe. However, strategies on TB prevention and successful treatment outcomes primarily target pulmonary TB. In this nationwide study, we present characteristics of EPTB, treatment outcomes, and predictors for unfavorable treatment outcomes. METHODS: All patients diagnosed with EPTB from 2009 to 2014 were included. Logistic regression analyses were used to identify risk factors for unfavorable outcome. The following definitions were used: unfavorable outcome: the sum of treatment failed, lost to follow-up, and not evaluated; patient delay: time from TB-related symptom onset until first hospital contact related to TB; doctor delay: time from first TB-related contact in the health care system to start of TB treatment. RESULTS: A total of 450 EPTB cases were notified, which represented 21.1% of all TB cases in Denmark. Immigrants accounted for 82.9%. Lymph nodes were the most common site of EPTB (55.4%) followed by pleural TB (13.4%). Patient delay was significantly longer among immigrants than Danes (60 vs 30 days; P < .01), whereas doctor delay was significantly longer among Danes (38.5 vs 28 days; P < .01). Treatment completion rates were high and reached 90.9% in 2014. Male gender (odds ratio [OR], 5.18; 95% confidence interval [CI], 1.79-15.04) and age 0-24 years (OR, 16.39; 95% CI, 2.02-132.64) were significantly associated with unfavorable outcome. CONCLUSIONS: EPTB represented a significant number of all TB cases and was predominantly seen among younger immigrants in Denmark. To maintain high treatment completion rates, increased focus on male gender and young age is needed.

Mycobacterium marinum infections in Denmark from 2004 to 2017: A retrospective study of incidence, patient characteristics, treatment regimens and outcome.

Mycobacterium marinum (M. marinum) is a slowly growing nontuberculous mycobacterium. The incidence of M. marinum infections in Denmark is unknown. We conducted a retrospective nationwide study including all culture confirmed cases of M. marinum from 2004 to 2017 in Denmark. All available medical records were reviewed. Demographics, clinical characteristics, and treatment regiments were analyzed. Fifty-five patients were identified, 40 (72.7%) were men with a median age of 50 years. Aquatic exposure was reported by 48 (90.6%) of the patients. Site of infection was upper extremities in 49 (92.5%) patients and 49 (92.5%) had superficial infection. The median time from symptom presentation to diagnosis was 194 days. All patients received antibiotics. Median time of treatment duration among all patients was 112 days. Treatment outcome was classified as improved in 40 (75%), improved with sequela in 4 (7.6%) patients and only 3 patients (3.8%) were classified as failed. Infection with M. marinum is rare and there is a long delay from symptom manifestation to diagnosis. The infection is predominantly related to aquatic exposure. M. marinum should be a differential diagnose in patients with slow-developing cutaneous elements and relevant exposure. Treatment outcomes are overall good and severe sequela are rare.

Prevalence of Sexual Experience and Initiation of Sexual Intercourse Among Adolescents, Rakai District, Uganda, 1994-2011.

PURPOSE: The purpose of the study was to identify risk factors and time trends for sexual experience and sexual debut in rural Uganda. METHODS: Using population-based, longitudinal data from 15- to 19-year olds in Rakai, Uganda, we examined temporal trends in the prevalence of sexual experience and potential risk factors for sexual experience (n = 31,517 person-round observations) using logistic regression. We then identified factors associated with initiation of sex between survey rounds, using Poisson regression to estimate incidence rate ratios (IRR; n = 5,126 person-year observations). RESULTS: Sexual experience was more common among adolescent women than men. The prevalence of sexual experience rose for most age-gender groups after 1994 and then declined after 2002. Factors associated with higher prevalence of sexual experience (without adjustment for other factors) included age, not enrolled in school, orphanhood, lower socioeconomic status, and drinking alcohol in the past 30 days; similar factors were associated with initiation of sex. Factors independently associated with initiation of sex included older age, nonenrollment in school (IRR = 1.7 for women and 1.8 for men), alcohol use (IRR = 1.3 for women and men), and being a double orphan among men (IRR = 1.2). Sexual experience began to decline around 2000, whereas increases in school enrollment began as early as 1994 and declines in orphanhood occurred after 2004 (as antiretroviral therapy became available). CONCLUSIONS: Sexual experience among youth in Rakai was associated with social factors particularly school enrollment. Changes in these social factors also appear to influence change over time in sexual experience.