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.

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.

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.

Heart disease among Greenlandic children and young adults: a nationwide cohort study.

BACKGROUND: The incidences of heart disease (HD) and congenital heart disease (CHD) among Inuit in Greenland (GL) and Denmark (DK) are unknown. This study aims to estimate incidence rates (IRs) of HD and CHD among the young Inuit populations in Greenland and Denmark compared with rates among young non-Inuit populations in the same countries. METHODS: A register-based nationwide cohort including all individuals living in Greenland and Denmark from birth to age <40 years through 1989-2014 was formed. Ethnicity was considered Inuit/mixed if at least one parent was registered as being born in Greenland. Information on HD and CHD hospitalization was obtained from national inpatient registers using ICD-8 and ICD-10 codes. RESULTS: HD IR was lower among individuals living in Greenland compared with those living in Denmark, [73.35GL (95% confidence interval (CI) 68.07 to 79.03)] vs [88.07DK (95% CI 87.38 to 88.76)], whereas CHD IRs were almost similar in the two countries [IR 34.44GL (95% CI 30.89 to 38.40) vs IR 34.67DK (95% CI 34.24 to 35.10)]. Being of Inuit/mixed ethnicity was associated with an increased risk of both HD and CHD compared with non-Inuit in Greenland and Denmark [adjusted hazard ratio HD 2.07GL (95% CI 1.25 to 3.42)] and CHD [2.92GL (95% CI 1.34 to 6.38)]. CONCLUSION: HD IR was lower in individuals living in Greenland compared with individuals living in Denmark, whereas the CHD IRs were almost the same for both countries. However, the risk of HD including CHD was higher among individuals of Inuit/mixed ethnicity compared with non-Inuit in both countries, suggesting a role of ethnicity among children and younger adults.

Loss of Sucrase-Isomaltase Function Increases Acetate Levels and Improves Metabolic Health in Greenlandic Cohorts.

BACKGROUND & AIMS: The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced. We aimed to describe the health of adults with sucrase-isomaltase deficiency. METHODS: The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings. RESULTS: Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index (ß [standard error], -2.0 [0.5] kg/m2; P = 3.1 × 10-5), body weight (-4.8 [1.4] kg; P = 5.1 × 10-4), fat percentage (-3.3% [1.0%]; P = 3.7 × 10-4), fasting triglyceride (-0.27 [0.07] mmol/L; P = 2.3 × 10-6), and remnant cholesterol (-0.11 [0.03] mmol/L; P = 4.2 × 10-5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (ß [standard error], 0.056 [0.002] mmol/L; P = 2.1 × 10-26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test. CONCLUSIONS: These results suggest that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health, and that the health benefits are mediated by reduced dietary sucrose uptake and possibly also by higher levels of circulating acetate.

Immunisation of healthcare workers in the Nordic countries: Variation in recommendations and practices and a lack of assessment.

Healthcare workers (HCWs) are at increased risk of both exposure and transmission of infectious disease. Two European Union (EU) directives state that health services are responsible for assessing their employees' potential exposure to infectious diseases and offering immunisation free of charge. We assessed current policy for immunisation of HCWs and the availability of vaccine coverage data in the Nordic countries by surveying national vaccination experts in Denmark, Finland, Iceland, Norway and Sweden, as well as Swedish county medical officers (CMOs). All national experts and 17 of 21 Swedish CMOs responded. All EU countries had transposed the European directives into national law, while Norway and Iceland had similar national legislation. Recommendations or guidelines were issued in Denmark, Finland, Iceland, Norway and 15 of 17 responding Swedish counties. The range of diseases covered differed by countries and Swedish counties. HCW vaccine coverage data were not systematically collected; incomplete estimates were only available for Finland and two Swedish counties. In conclusion, recommendations or guidelines exist in the Nordic countries, but their impact cannot be assessed, as vaccine uptake among HCWs is not currently measured. Systematic collection of data is a necessary step towards improving HCW immunisation policy and practice in the Nordic countries.

Strategic health communication on social media: Insights from a Danish social media campaign to address HPV vaccination hesitancy.

OBJECTIVE: To evaluate whether the social media strategy developed for the campaign Stop HPV - stop cervical cancer was successful at engaging target groups in communication regarding HPV vaccination. INTRODUCTION: In 2009, the Human Papillomavirus (HPV) vaccine became part of the Danish childhood vaccination program to protect Danish girls from cervical cancer. In 2015, after a period of massive media coverage questioning the safety of the HPV vaccination, a rapid decline in HPV vaccination coverage was observed. An information campaign was therefore launched in May 2017 to address HPV vaccination hesitancy. THE SOCIAL MEDIA STRATEGY: 'Heart-brain communication' combined facts and emotions through varied content. Community management guidelines were worked out to ensure that there was positive dialogue. Key Point Indicators (KPI) for Engagement Rate (ER) and Click Through Rate (CTR) were chosen to uphold engagement and traffic from Facebook to the website. The KPIs were used to measure effectiveness. RESULTS: In January 2019, the social media campaign had reached 8,020,000 people with an average of 127 comments per post. The average ER from May 2017 to halfway through 2018 was 6.07% and the CTR was 2.09%. The content subgroup personal stories was the most effective in creating positive dialogue. One year after the launch of the campaign, the number of positive comments had increased from less than 50% to approximately 75%. CONCLUSION: A comprehensive social media strategy using 'heart-brain communication' proved useful in a campaign for HPV vaccination. The success of the social media strategy was due to meticulous planning prior to launching the campaign, the use of content subgroups, the allocation of adequate resources for community management, the empirical analysis of content, and the use of evaluation results as guidance for the production of new content.

Using Facebook to increase coverage of HPV vaccination among Danish girls: An assessment of a Danish social media campaign.

OBJECTIVES: In this study we assess how different Facebook (FB) posts resonate with parents hesitant about HPV vaccination and how to engage parents in positive dialogues on FB. BACKGROUND: Vaccination against human papillomavirus (HPV) was successfully introduced in the Danish childhood vaccination program in 2009 for 12 year-old girls, with coverage reaching approximately 90%. However, negative public debate questioning the safety of the vaccine coincided with a rapid decline in vaccination coverage from 2015. In May 2017, we launched the national campaign Stop HPV - stop cervical cancer with the aim to rebuild trust in the HPV vaccine and increase vaccination coverage. We used a FB page and a social media strategy to engage the campaign's primary target group: mothers hesitant about HPV vaccination of their daughters. METHODS: We analyzed a variety of posts on the FB page Stop HPV - stop cervical cancer posted from May 2017 to December 2017. We performed analysis documenting post reach, engagement in the posts and sentiment (positive, neutral or negative) of the comments. Focus groups were recruited to provide data about attitudes to the posts and the responses from the FB management team. RESULTS: 84 unique posts were published on the FB page from May 2017 to December 2017 reaching 3,476,023 individual FB profiles. In focus groups, parents requested more in-depth information. However, analyses of FB posts and sentiment of comments showed that personal stories generated higher engagement rates and more positive dialogues compared to factual posts. CONCLUSION: The FB page Stop HPV - stop cervical cancer has successfully reached and engaged FB users in dialogue about HPV vaccination. Personal stories are effective in creating positive dialogues on FB. However, it remains important to provide factual information to parents to enable informed decision making about HPV vaccination.

The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders.

The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body mass index (BMI), to expand the knowledge of the genetic and biological mechanisms underlying obesity. Stage 1 BMI-association analyses were performed in 4,626 Greenlanders. Stage 2 replication and meta-analysis were performed in additional cohorts comprising 1,058 Yup'ik Alaska Native people, and 1,529 Greenlanders. Obesity-related traits were assessed in the stage 1 study population. We identified a common variant on chromosome 11, rs4936356, where the derived G-allele had a frequency of 24% in the stage 1 study population. The derived allele was genome-wide significantly associated with lower BMI (beta (SE), -0.14 SD (0.03), p = 3.2x10-8), corresponding to 0.64 kg/m2 lower BMI per G allele in the stage 1 study population. We observed a similar effect in the Yup'ik cohort (-0.09 SD, p = 0.038), and a non-significant effect in the same direction in the independent Greenlandic stage 2 cohort (-0.03 SD, p = 0.514). The association remained genome-wide significant in meta-analysis of the Arctic cohorts (-0.10 SD (0.02), p = 4.7x10-8). Moreover, the variant was associated with a leaner body type (weight, -1.68 (0.37) kg; waist circumference, -1.52 (0.33) cm; hip circumference, -0.85 (0.24) cm; lean mass, -0.84 (0.19) kg; fat mass and percent, -1.66 (0.33) kg and -1.39 (0.27) %; visceral adipose tissue, -0.30 (0.07) cm; subcutaneous adipose tissue, -0.16 (0.05) cm, all p<0.0002), lower insulin resistance (HOMA-IR, -0.12 (0.04), p = 0.00021), and favorable lipid levels (triglyceride, -0.05 (0.02) mmol/l, p = 0.025; HDL-cholesterol, 0.04 (0.01) mmol/l, p = 0.0015). In conclusion, we identified a novel variant, where the derived G-allele possibly associated with lower BMI in Arctic populations, and as a consequence also leaner body type, lower insulin resistance, and a favorable lipid profile.

Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit.

N-acetyltransferase 2 (NAT2) is the main enzyme metabolizing isoniazid and genotype-based treatment has been studied for years without becoming common practice. To investigate whether genotype-based isoniazid treatment is feasible in Greenland, we sequenced the coding sequence of NAT2 and determined the NAT2 enzyme-activity by caffeine test. No additional genetic variants were identified in the coding sequence of NAT2, so that genotype status in 260 study participants could be assessed by a well-established 7-SNP panel. Studying the enzyme activity by the ratio of the two caffeine metabolites AFMU and 1X in 260 participants showed a high rate of slow phenotypes with intermediate or rapid genotype. These misclassifications were mainly observed in urine samples with pH<3, a deviation from the standard protocol due to the field work character of the study, where immediate pH adjustment to pH=3.5 was not possible. We excluded these samples. For the remaining 143 individuals with pH>3, we observed a moderate level of discrepancies (19 of the 116 individuals with intermediate or rapid genotype status having a slow phenotype). Further investigation showed that drinking coffee and not tea or cola was the most important factor for high levels of both metabolites. The concordance between phenotype and genotype status with regard to slow metabolism supported the recommendation of lower isoniazid doses in individuals with slow genotype status in order to avoid liver injury, a frequent side effect. The phenotypical variation observed for individuals with intermediate or rapid genotype status warrants further research before increased dosing of isoniazid can be recommended.

Determinants of tuberculosis trends in six Indigenous populations of the USA, Canada, and Greenland from 1960 to 2014: a population-based study.

BACKGROUND: Tuberculosis continues to disproportionately affect many Indigenous populations in the USA, Canada, and Greenland. We aimed to investigate whether population-based tuberculosis-specific interventions or changes in general health and socioeconomic indicators, or a combination of these factors, were associated with changes in tuberculosis incidence in these Indigenous populations. METHODS: For this population-based study we examined annual tuberculosis notification rates between 1960 and 2014 in six Indigenous populations of the USA, Canada, and Greenland (Inuit [Greenland], American Indian and Alaska Native [Alaska, USA], First Nations [Alberta, Canada], Cree of Eeyou Istchee [Quebec, Canada], Inuit of Nunavik [Quebec, Canada], and Inuit of Nunavut [Canada]), as well as the general population of Canada. We used mixed-model linear regression to estimate the association of these rates with population-wide interventions of bacillus Calmette-Guérin (BCG) vaccination of infants, radiographic screening, or testing and treatment for latent tuberculosis infection (LTBI), and with other health and socioeconomic indicators including life expectancy, infant mortality, diabetes, obesity, smoking, alcohol use, crowded housing, employment, education, and health expenditures. FINDINGS: Tuberculosis notification rates declined rapidly in all six Indigenous populations between 1960 and 1980, with continued decline in Indigenous populations in Alberta, Alaska, and Eeyou Istchee thereafter but recrudescence in Inuit populations of Nunavut, Nunavik, and Greenland. Annual percentage reductions in tuberculosis incidence were significantly associated with two tuberculosis control interventions, relative to no intervention, and after adjustment for infant mortality and smoking: BCG vaccination (-11%, 95% CI -6 to -17) and LTBI screening and treatment (-10%, -3 to -18). Adjusted associations were not significant for chest radiographic screening (-1%, 95% CI -7 to 5). Declining tuberculosis notification rates were significantly associated with increased life expectancy (-37·8 [95% CI -41·7 to -33·9] fewer cases per 100 000 for each 1-year increase) and decreased infant mortality (-9·0 [-9·5 to -8·6] fewer cases per 100 000 for each death averted per 1000 livebirths) in all six Indigenous populations, but no significant associations were observed for other health and socioeconomic indicators examined. INTERPRETATION: Population-based BCG vaccination of infants and LTBI screening and treatment were associated with significant decreases in tuberculosis notification rates in these Indigenous populations. These interventions should be reinforced in populations still affected by tuberculosis, while also addressing the persistent health and socioeconomic disparities. FUNDING: Public Health Department of the Cree Board of Health and Social Services of James Bay.

Increased incidence of gonorrhoea and chlamydia in Greenland 1990-2012.

BACKGROUND: Since the 1970s, Greenland has presented the highest reported incidence rates of the sexually transmitted infections (STIs) gonorrhoea and chlamydia in the Arctic regions. OBJECTIVE: This study aims to describe sex- and age-specific incidence rates of gonorrhoea and chlamydia from 1990 to 2012 in Greenland, and to evaluate if changes in case definitions, diagnostic procedures and implementation of STI interventions during the period coincide with rate changes. DESIGN: Gonorrhoea and chlamydia cases were identified from the national STI surveillance. For 1990-2008, STI cases were identified from weekly notified aggregated data. For 2009-2012, cases were identified in person-identifiable national registers. We used log-linear Poisson regression to calculate incidence rates (IRs) and incidence rate ratios (IRRs) with 95% confidence intervals (95% CI). Analyses were stratified according to sex, age and calendar period. RESULTS: Gonorrhoea and chlamydia incidence rates have increased since 1995 to reach 2,555 per 100,000 person-years (PY) for gonorrhoea and 6,403 per 100,000 PY for chlamydia in 2012. From 2006 to 2012, the incidence rates among young adults aged 15-19 years were 8,187 and 22,515 per 100,000 PY for gonorrhoea and chlamydia, respectively. Changes in surveillance reporting did not seem to influence the incidence rates for either disease, whereas a change in diagnostic test coincided with an increased incidence of chlamydia. CONCLUSION: Overall, the incidence of chlamydia in Greenland increased during the study period, whereas the incidence of gonorrhoea decreased until 1995 but increased thereafter. Young adults aged 15-24 years were at highest risk of infection. The increase in incidence rates was independent of changes in case definitions, whereas an observed increase in chlamydia incidence in 2005 coincided with a change in diagnostic test. None of the STI interventions launched after 1995 seemed to coincide with decreasing national incidence rates.

The dynamics of immune responses to Mycobacterium tuberculosis during different stages of natural infection: A longitudinal study among Greenlanders.

OBJECTIVE: Understanding human immunity to Mycobacterium tuberculosis (Mtb) during different stages of infection is important for development of an effective tuberculosis (TB) vaccine. We aimed to evaluate immunity to Mtb infection by measuring immune responses to selected Mtb antigens expressed during different stages of infection over time and to observe sustainability of immunity. METHODS: In a cohort study comprising East Greenlanders aged 17-22 years (2012 to 2014) who had either; undetectable Mtb infection, ongoing or prior Mtb infection at enrolment, we measured immunity to 15 antigens over a one-year period. Quantiferon-TB Gold testing (QFT) defined Mtb infection status (undetected/detected). The eligible study population of East Greenlanders aged 17-22 years was identified from the entire population using the Civil Registration System. From the source population 65 participants were selected by stratified random sampling according to information on Mtb infection stage. Retrospective and prospective information on notified TB (including treatment) was obtained through the mandatory TB notification system and was used to characterise Mtb infection stage (ongoing/prior). Immunity to 15 antigens including two QFT antigens, PPD and 12 non-QFT antigens (representing early, constitutive and latent Mtb infection) was assessed by measuring immune responses using whole-blood antigen stimulation and interferon gamma measurement. RESULTS: Of 65 participants, 54 were considered Mtb-infected. Immunity to Mtb infection fluctuated with high annual risk of conversion (range: 6-69%) and reversion (range: 5-95%). During follow-up, five (8%) participants were notified with TB; neither conversion nor reversion was associated with an increased risk of progressing to TB. CONCLUSIONS: Our findings suggest that human immunity to natural Mtb infection over time is versatile with fluctuations, resulting in high levels of conversion and reversion of immunity, thus human immunity to Mtb is much more dynamic than anticipated. The study findings suggest future use of longitudinal assessment of immune responses when searching for TB vaccine candidate antigens.

CPT1A Missense Mutation Associated With Fatty Acid Metabolism and Reduced Height in Greenlanders.

BACKGROUND: Inuit have lived for thousands of years in an extremely cold environment on a diet dominated by marine-derived fat. To investigate how this selective pressure has affected the genetic regulation of fatty acid metabolism, we assessed 233 serum metabolic phenotypes in a population-based sample of 1570 Greenlanders. METHODS AND RESULTS: Using array-based and targeted genotyping, we found that rs80356779, a p.Pro479Leu variant in CPT1A, was strongly associated with markers of n-3 fatty acid metabolism, including degree of unsaturation (P=1.16×10-34), levels of polyunsaturated fatty acids, n-3 fatty acids, and docosahexaoenic acid relative to total fatty acid levels (P=2.35×10-15, P=4.02×10-19, and P=7.92×10-27). The derived allele (L479) occurred at a frequency of 76.2% in our sample while being absent in most other populations, and we found strong signatures of positive selection at the locus. Furthermore, we found that each copy of L479 reduced height by an average of 2.1 cm (P=1.04×10-9). In exome sequencing data from a sister population, the Nunavik Inuit, we found no other likely causal candidate variant than rs80356779. CONCLUSION: Our study shows that a common CPT1A missense mutation is strongly associated with a range of metabolic phenotypes and reduced height in Greenlanders. These findings are important from a public health perspective and highlight the usefulness of complex trait genetic studies in isolated populations.

National clinical guidelines for non-surgical treatment of patients with recent onset neck pain or cervical radiculopathy.

PURPOSE: To summarise recommendations about 21 selected non-surgical interventions for recent onset (<12 weeks) non-specific neck pain (NP) and cervical radiculopathy (CR) based on two guidelines from the Danish Health Authority. METHODS: Two multidisciplinary working groups formulated recommendations based on the GRADE approach. RESULTS: Twelve recommendations were based on evidence and nine on consensus. Management should include information about prognosis, warning signs, and advise to remain active. For treatment, guidelines suggest different types of supervised exercise and manual therapy; combinations of exercise and manual therapy before medicine for NP; acupuncture for NP but not CR; traction for CR; and oral NSAID (oral or topical) and Tramadol after careful consideration for NP and CR. CONCLUSION: Recommendations are based on low-quality evidence or on consensus, but are well aligned with recommendations from guidelines from North America. The working groups recommend intensifying research relating to all aspects of management of NP and CR.

Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6.

There is a need for an improved vaccine for tuberculosis. ESAT-6 is a cardinal vaccine antigen with unique properties and is included in several vaccine candidates in development. ESAT-6 is also the core antigen in the IFN-γ release assays (IGRA) used to diagnose latent infection, rendering IGRA tests unspecific after vaccination. This challenge has prompted the development of a companion diagnostic for ESAT-6 based vaccines, an ESAT-6 free IGRA. We screened a panel of seven potential new diagnostic antigens not recognized in BCG vaccinated individuals. Three highly recognized antigens EspC, EspF and Rv2348c were identified and combined with CFP10 in an ESAT-6 free antigen cocktail. The cocktail was prepared in a field-friendly format, lyophilized with heparin in ready-to-use vacutainer tubes. The diagnostic performance of the ESAT-6 free IGRA was determined in a cross-validation study. Compared IGRA, the ESAT-6 free IGRA induced a comparable magnitude of IFN-γ release, and the diagnostic performance was on par with Quantiferon (sensitivity 84% vs 79%; specificity 99% vs 97%). The comparable performance of the ESAT-6 free IGRA to IGRA suggests potential as companion diagnostic for ESAT-6 containing vaccines and as adjunct test for latent infection.