The impact of living conditions and health interventions on tuberculosis, Denmark, 1876 to 2022.

BackgroundDenmark possesses an exceptional historical data collection on tuberculosis (TB) from 1876 to the present, providing a unique opportunity to assess TB epidemiology over 147 years in Denmark.AimOur aim was to describe the TB disease burden in Denmark in relation to historical events, living conditions and health interventions during the past 147 years.MethodsWe performed a nationwide register-based ecological study including all persons with TB in Denmark from 1876 through 2022, correlating the TB incidence to social, economic and health indicators.ResultsIn Denmark, the overall TB incidence and mortality declined markedly over the past 147 years, only marginally influenced by specific TB interventions such as sanatoria, Bacillus Calmette-Guèrin (BCG) vaccination, mass screenings and antibiotics. Parallel to this decline, the country experienced improved living conditions, as illustrated by decreased infant mortality and increased life expectancy and wealth. In 1978, Denmark became a low-incidence country for TB with risk groups predominantly affected, and with a continuous change in demographics towards fewer Danish-born cases and relatively more migrant cases.ConclusionsThe decline over time in TB incidence and mortality in Denmark preceded specific TB interventions and can, first of all, be attributed to improved living conditions. TB has now become a rare disease in Denmark, predominantly occurring in particular risk groups. Future elimination of TB will require a combination of specific health interventions in these risk groups combined with a continued focus on improving socioeconomic status and living conditions.

Pertussis epidemic in Denmark, August 2023 to February 2024.

We report a record high pertussis epidemic in Denmark since August 2023. Highest incidence was in adolescents, while peak incidence in infants was lower vs previous epidemics in 2019 and 2016. Among infants aged 0-2 months, over half (29/48) were hospitalised and one infant died, underlining the disease severity in the youngest. To protect infants, pertussis vaccination in pregnant women was introduced in January 2024 in the national vaccination programme. Improved vaccination surveillance in pregnant women is being implemented.

Mycoplasma pneumoniae epidemic in Denmark, October to December, 2023.

We report a surge of patients, especially children and adolescents, with respiratory disease caused by Mycoplasma pneumoniae in Denmark since October 2023. While the surge has reached an epidemic level, no impact on hospital capacity has been observed; only 14% (446/3,195) of cases, primarily adults, required hospitalisation. Macrolide resistance was detected in less than 2% of samples tested. Timely monitoring of hospitalisations linked to M. pneumoniae infections has been established to inform the healthcare system, decisionmakers and the public.

Epidemic of parvovirus B19 and disease severity in pregnant people, Denmark, January to March 2024.

We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.

Excess mortality in Europe coincides with peaks of COVID-19, influenza and respiratory syncytial virus (RSV), November 2023 to February 2024.

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI:  91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

Pregnancy and post-partum tuberculosis; a nationwide register-based case-control study, Denmark, 1990 to 2018.

BackgroundPregnancy increases the risk of tuberculosis (TB), however, data on TB epidemiology in pregnant women are limited.AimTo guide possible interventions, we analysed risk factors for TB in pregnant and post-partum women.MethodsWe conducted a nationwide retrospective register-based case-control study from January 1990 to December 2018 in Denmark. Cases were women diagnosed with TB during their pregnancy or in the post-partum period. We selected two control groups: pregnant or post-partum women without TB, and non-pregnant women with TB. Differences were assessed by chi-squared or Fisher's exact test. Risk factors for TB were identified through logistic regression and estimated by odds ratio (OR).ResultsWe identified 392 cases, including 286 pregnant and 106 post-partum women. Most were migrants (n = 366; 93%) with a shorter median time spent in Denmark (2.74 years; interquartile range (IQR): 1.52-4.64) than non-pregnant TB controls (3.98 years; IQR: 1.43-8.51). Cases less likely had a Charlson comorbidity index ≥ 2compared with non-pregnant TB controls (p < 0.0001), and had no increased risk of severe disease (p = 0.847). Migrants from other World Health Organization regions than Europe, especially Africa (OR: 187; 95%CI: 125-281) had persistently higher odds of TB.ConclusionsIn Denmark, the risk of TB in pregnant and post-partum women is increased in migrant women who have stayed in the country a median time of approximately 3 years. We recommend increased focus on TB risk during pregnancy and suggest evaluating targeted TB screening of selected at-risk pregnant women to promote early case finding and prevent TB among mothers and their newborn children.

Eikenella corrodens endocarditis and liver abscess in a previously healthy male, a case report.

BACKGROUND: Eikenella corrodens is one of the HACEK bacteria constituting part of the normal flora of the oropharynx, however, still an uncommon pathogen. We report a case of a large Eikenella corrodens liver abscess with simultaneously endocarditis in a previously healthy male. CASE PRESENTATION: A 49-year-old Danish man was admitted because of one-month malaise, fever, cough and unintentional weight loss. On admission there was elevated white blood cell count and C-reactive protein, as well as affected liver function tests. Initially pneumonia was suspected, but due to lack of improvement on pneumonia treatment, a PET-CT scan was performed, which showed a large multiloculated abscess in the liver. The abscess was drained using ultrasound guidance. Culture demonstrated Eikenella corrodens. Transesophageal echocardiography revealed aortic endocarditis. The patient was treated with antibiotics and abscess drainage, on which he slowly improved. He was discharged after 1.5 months of hospitalisation. On follow-up 2 months later, the patient was asymptomatic with normalized biochemistry and ultrasound showed complete regression of the abscess. CONCLUSIONS: This is the first case of documented Eikenella corrodens concurrent liver abscess and endocarditis. The case report highlights that Eikenella corrodens should be considered as a cause of liver abscess. Empirical treatment of pyogenic liver abscess will most often cover Eikenella corrodens, but the recommended treatment is a third generation cephalosporin or a fluoroquinolon. A multiloculated liver abscess may require drainage several times during treatment. The finding of Eikenella corrodens should elicit an echocardiography to diagnose endocarditis even in patients without clinical signs of endocarditis.

Determination of NAT2 acetylation status in the Greenlandic population.

N-acetyltransferase 2 (NAT2) is a well-studied phase II xenobiotic metabolizing enzyme relevant in drug metabolism and cancerogenesis. NAT2 activity is largely determined by genetic polymorphisms in the coding region of the corresponding gene. We investigated NAT2 acetylation status in 1556 individuals from Greenland based on four different single nucleotide polymorphism (SNP) panels and the tagging SNP rs1495741. There was good concordance between the NAT2 status inferred by the different SNP combinations. Overall, the fraction of slow acetylators was low with 17.5 % and varied depending on the degree of Inuit ancestry; in individuals with <50 % Inuit ancestry, we observed more than 25 % slow acetylators reflecting European ancestry. Greenland has a high incidence of tuberculosis, and individual dosing of isoniazid according to NAT2 status has been shown to improve treatment and reduce side effects. Our findings could be a first step in pharmacogenetics-based tuberculosis therapy in Greenland.

Mortality, risk factors, and causes of death among people with tuberculosis in Denmark, 1990-2018.

OBJECTIVES: This study aimed to analyze mortality, risk factors, and causes of death among people with tuberculosis (TB). METHODS: This is a population-based cohort study with patients with TB ≥18 years notified from 1990 to 2018 in Denmark, compared with sex- and age-matched controls. Mortality was assessed in Kaplan-Meier models and risk factors for death were estimated in Cox proportional hazards models. RESULTS: Overall mortality was twofold higher among people with TB compared with controls up to 15 years after TB diagnosis (hazard ratio [HR]: 2.18, 95% confidence interval [CI]: 2.06-2.29, P <0.0001). Danes with TB were three times more likely to die than migrants (adjusted HR: 3.13, 95% CI: 2.84-3.45, P <0.0001). Risk factors for death included living alone, being unemployed, having low income, and comorbidities such as mental illness with substance abuse, lung diseases, hepatitis, and HIV. TB was the most common cause of death (21%), followed by chronic obstructive pulmonary disease (7%), lung cancer (6%), alcoholic liver disease (5%), and mental illness with substance abuse (4%). CONCLUSION: People with TB had substantially inferior survival up to 15 years after TB diagnosis, in particular, socially disadvantaged Danes with TB with specific comorbidities. This may reflect unmet needs for enhanced treatment of other medical/social conditions during TB treatment.

Mortality and Cause of Death in Children With Presumptive Disseminated Tuberculosis.

BACKGROUND AND OBJECTIVES: Children experience high tuberculosis (TB)-related mortality but causes of death among those with presumptive TB are poorly documented. We describe the mortality, likely causes of death, and associated risk factors among vulnerable children admitted with presumptive TB in rural Uganda. METHODS: We conducted a prospective study of vulnerable children, defined as <2 years of age, HIV-positive, or severely malnourished, with a clinical suspicion of TB. Children were assessed for TB and followed for 24 weeks. TB classification and likely cause of death were assessed by an expert endpoint review committee, including insight gained from minimally invasive autopsies, when possible. RESULTS: Of the 219 children included, 157 (71.7%) were <2 years of age, 72 (32.9%) were HIV-positive, and 184 (84.0%) were severely malnourished. Seventy-one (32.4%) were classified as "likely tuberculosis" (15 confirmed and 56 unconfirmed), and 72 (32.9%) died. The median time to death was 12 days. The most frequent causes of death, ascertained for 59 children (81.9%), including 23 cases with autopsy results, were severe pneumonia excluding confirmed TB (23.7%), hypovolemic shock due to diarrhea (20.3%), cardiac failure (13.6%), severe sepsis (13.6%), and confirmed TB (10.2%). Mortality risk factors were confirmed TB (adjusted hazard ratio [aHR] = 2.84 [95% confidence interval (CI): 1.19-6.77]), being HIV-positive (aHR = 2.45 [95% CI: 1.37-4.38]), and severe clinical state on admission (aHR = 2.45 [95% CI: 1.29-4.66]). CONCLUSIONS: Vulnerable children hospitalized with presumptive TB experienced high mortality. A better understanding of the likely causes of death in this group is important to guide empirical management.

Social determinants of tuberculosis: a nationwide case-control study, Denmark, 1990-2018.

BACKGROUND: The global vision is a world free of tuberculosis (TB). Even in resource-rich TB low-incidence settings, we need more focus on the role of social risk factors to end the TB epidemic. METHODS: Nationwide, retrospective register-based, case-control study from 1990 to 2018, including all TB patients in Denmark ≥18 years old (n = 9581) matched 1:3 on sex and age with population controls. TB risk factors were assessed in logistic regression models and estimated by odds ratio (OR). RESULTS: All TB patients had considerably lower socio-economic status compared with controls (P < 0.0001). Among ethnic Danes, TB was mostly found among males, persons between 35 and 65 years, those living alone, those with low educational level, persons on social welfare benefits and those with low income. Conversely, for migrants, being younger, sex and living alone were less important, whereas having children was protective. In an adjusted multivariable regression model among Danes, key risk factors for TB were being on disability pension (OR = 2.7) and cash benefits (OR = 4.7). For migrants, fewer social risk factors increased TB risk, although low income and cash benefits did (OR = 3.1). CONCLUSION: Even today in a resourceful setting, socio-economic status drives disparities in health. In our study, multifactorial social deprivation was highly associated with TB. Especially household structure, education, employment and income were important risk factors that should be addressed in the future to accelerate TB control and end the TB epidemic.

[Isoniazid-inducedtoxic hepatitis].

Hepatotoxicity is a well-known side effect to isoniazid treatment with the risk of progression to liver failure. This case report describes a 39-year-old male, who received standard isoniazid treatment for latent TB infection (LTBI) and developed severe isoniazid-induced acute hepatitis. Liver transplantation was considered, but the patient slowly recovered with full hepatic regeneration. With increasing focus on treating LTBI in Denmark, routine follow-up including biochemical monitoring should be implemented for patients receiving LTBI treatment to prevent severe complications.

The Epidemiology and Clinical Characteristics of Pediatric Tuberculosis in Denmark 2009-2014 Highlights Targets for Prevention.

BACKGROUND: In Western Europe, most pediatric tuberculosis (TB) cases occur among immigrants; however, data are rarely stratified by first/second-generation immigrants and many cases may be preventable. METHODS: This was a nationwide study of children <18 years with TB from 2009 to 2014 in Denmark. Demographic, clinical, microbiologic and treatment outcome data were obtained from registers and medical records. RESULTS: We identified 145 cases; 99 were immigrants (68%) of which 54 (55%) were second-generation immigrants. Most first-generation immigrants (73%) were diagnosed by passive case finding as was half the second-generation immigrants (52%), in contrast to Danish children who were mostly diagnosed by active case finding (70%). Symptoms were often nonspecific, and one-third of the children had normal blood tests at time of diagnosis. First-generation immigrants were most often infected abroad (84%) as opposed to Danish children (9%) and second-generation immigrants (30%). Approximately one-third of the children represented cases of TB disease that could possibly have been prevented by screening or rigorous contact tracing. The overall treatment success rate was 97%, and cases of unsuccessful treatment were restricted to immigrant adolescents. CONCLUSIONS: The majority of pediatric TB in Denmark occurred among immigrant children with symptomatic TB, whereas more Danish children were diagnosed at earlier disease stages. Almost one-third of TB cases may represent missed opportunities to prevent TB disease. Improvements include enhanced adult case detection with comprehensive contact investigation among children, tailored screening and vaccination of immigrant children, and raised awareness of diagnosing and treating latent TB infection in children.

Leptospirosis meningitis transmission from a pet mouse: a case report.

BACKGROUND: Leptospirosis is a reemerging zoonosis with a worldwide distribution and a wide range of clinical manifestations. We report a case of leptospirosis meningitis in a previously healthy woman infected by her pet mouse. CASE PRESENTATION: A 27-year-old Caucasian woman with pet mice presented to our institute with a 1 week history of fever, headache, myalgia, vomiting, diarrhea, and dark urine. Her admission examination revealed neck stiffness, conjunctivitis, and icteric sclera. Her liver enzymes, bilirubin, white blood cell count, and C-reactive protein were elevated. Her cerebrospinal fluid showed an elevated white blood cell count. Polymerase chain reactions using her cerebrospinal fluid, blood, and urine showed negative results for leptospirosis, but the result of her microagglutination test was positive for Leptospira interrogans serovar sejroe with a more than threefold increase in paired sera. The patient was treated with ceftriaxone for 1 week, and her condition steadily improved. CONCLUSIONS: This case report raises awareness of pet rodents as sources of leptospirosis. Leptospirosis meningitis should be considered in patients with meningeal symptoms and pet rodents.

Tuberculosis Transmission in Danish Children: A Nationwide Register-based Study.

BACKGROUND: Tuberculosis (TB) remains a major public health issue among children worldwide. Data on TB transmission in children living in low-incidence countries is limited. METHODS: We studied TB transmission in ethnic Danish children younger than 15 years of age between 2000 and 2013. Identification of children with TB disease and information on demographics and TB contacts were retrieved from the national TB surveillance register and the International Reference Laboratory of Mycobacteriology. RESULTS: In total, 88 children with TB disease were identified in the study period, corresponding to a mean annual incidence of 6.9 per 1,000,000 children younger than 15 years of age. The male to female ratio was 1.3. Median age was 5 years (interquartile range, 3-8.5). Seventy-three (83%) children had a known TB contact of which 60% was among household contacts with recent TB, predominantly parents. Sixty-six (75%) children were classified as part of epidemiologic clusters. Thirty-five (40%) children had culture verified TB of which information on genotypes was available for 34 (97%). Of these, 35% belonged to cluster C2/1112-15, the most prevalent cluster among adult Danes. CONCLUSIONS: We found on-going TB transmission in Danish children within the households of a low TB incidence population. These findings emphasize the need for early diagnosis of TB in children, thorough contact tracing and increased focus on risk groups.

[Testing for latent tuberculosis infection needs to be improved in Denmark].

Tuberculosis (TB) remains a public health emergency worldwide. WHO recommends low-incidence countries to increase awareness of latent tuberculosis infection (LTBI) as part of a national preventive strategy. This review focuses on the burden of TB in Denmark, which might be reduced, if more focus was paid on diagnosing LTBI in relevant patients, and treatment to prevent future active TB cases was initiated. LTBI testing should be considered in persons at risk of TB disease, who will benefit from LTBI treatment, e.g. recently infected persons or persons having undergone organ transplantation or having comorbidity such as HIV, dialyses, and immunosuppression.

CNS infections in Greenland: A nationwide register-based cohort study.

BACKGROUND: Indigenous Arctic people suffer from high rates of infectious diseases. However, the burden of central nervous system (CNS) infections is poorly documented. This study aimed to estimate incidence rates and mortality of CNS infections among Inuits and non-Inuits in Greenland and in Denmark. METHODS: We conducted a nationwide cohort study using the populations of Greenland and Denmark 1990-2012. Information on CNS infection hospitalizations and pathogens was retrieved from national registries and laboratories. Incidence rates were estimated as cases per 100,000 person-years. Incidence rate ratios were calculated using log-linear Poisson-regression. Mortality was estimated using Kaplan-Meier curves and Log Rank test. RESULTS: The incidence rate of CNS infections was twice as high in Greenland (35.6 per 100,000 person years) as in Denmark (17.7 per 100,000 person years), but equally high among Inuits in Greenland and Denmark (38.2 and 35.4, respectively). Mortality from CNS infections was 2 fold higher among Inuits (10.5%) than among non-Inuits (4.8%) with a fivefold higher case fatality rate in Inuit toddlers. CONCLUSION: Overall, Inuits living in Greenland and Denmark suffer from twice the rate of CNS infections compared with non-Inuits, and Inuit toddlers carried the highest risk of mortality. Further studies regarding risk factors such as genetic susceptibility, life style and socioeconomic factors are warranted.