Age-dependent influenza infection patterns and subtype circulation in Denmark, in seasons 2015/16 to 2021/22.

BackgroundInfluenza was almost absent for 2 years following the implementation of strict public health measures to prevent the spread of SARS-CoV-2. The consequence of this on infections in different age groups is not yet known.AimTo describe the age groups infected with the influenza virus in 2021/22, the first post-pandemic influenza season in Denmark, compared with the previous six seasons, and subtypes circulating therein.MethodsInfection and hospitalisation incidences per season and age group were estimated from data in Danish registries. Influenza virus subtypes and lineages were available from samples sent to the National Influenza Centre at Statens Serum Institut.ResultsTest incidence followed a similar pattern in all seasons, being highest in 0-1-year-olds and individuals over 75 years, and lowest in 7-14-year-olds and young people 15 years to late twenties. When the influenza A virus subtypes A(H3N2) and A(H1N1)pdm09 co-circulated in seasons 2015/16 and 2017/18 to 2019/20, the proportion of A(H1N1)pdm09 was higher in 0-1-year-olds and lower in the over 85-year-olds compared with the overall proportion of A(H1N1)pdm09 in these seasons. The proportion of A(H3N2) was higher in the over 85 years age group compared with the overall proportion of A(H3N2). The 2016/17 and 2021/22 seasons were dominated by A(H3N2) but differed in age-specific trends, with the over 85 years age group initiating the 2016/17 season, while the 2021/22 season was initiated by the 15-25-year-olds, followed by 7-14-year-olds.ConclusionThe 2021/22 influenza season had a different age distribution compared with pre-COVID-19 pandemic seasons.

Frequency of pleural effusion in dengue patients by severity, age and imaging modality: a systematic review and meta-analysis.

BACKGROUND: Identification of pleural effusion (PE) in dengue infection is an objective measure of plasma leakage and may predict disease progression. However, no studies have systematically assessed the frequency of PE in patients with dengue, and whether this differs across age and imaging modality. METHODS: We searched Pubmed, Embase Web of Science and Lilacs (period 1900-2021) for studies reporting on PE in dengue patients (hospitalized and outpatient). We defined PE as fluid in the thoracic cavity detected by any imaging test. The study was registered in PROSPERO (CRD42021228862). Complicated dengue was defined as hemorrhagic fever, dengue shock syndrome or severe dengue. RESULTS: The search identified 2,157 studies of which 85 studies were eligible for inclusion. The studies (n = 31 children, n = 10 adults, n = 44 mixed age) involved 12,800 patients (30% complicated dengue). The overall frequency of PE was 33% [95%CI: 29 to 37%] and the rate of PE increased significantly with disease severity (P = 0.001) such that in complicated vs. uncomplicated dengue the frequencies were 48% and 17% (P < 0.001). When assessing all studies, PE occurred significantly more often in children compared to adults (43% vs. 13%, P = 0.002) and lung ultrasound more frequently detected PE than conventional chest X-ray (P = 0.023). CONCLUSIONS: We found that 1/3 of dengue patients presented with PE and the frequency increased with severity and younger age. Importantly, lung ultrasound demonstrated the highest rate of detection. Our findings suggest that PE is a relatively common finding in dengue and that bedside imaging tools, such as lung ultrasound, potentially may enhance detection.

Early and intense epidemic of respiratory syncytial virus (RSV) in Denmark, August to December 2022.

In the autumn of 2022, Denmark witnessed the second out-of-season epidemic of respiratory syncytial virus (RSV) following widespread societal preventive measures implemented against the coronavirus disease (COVID-19) pandemic during 2020 and 2021. Admissions peaked at twice the level of pre-pandemic seasons. Especially infants below 6 months of age were affected, but also adults over 45 years of age. The current epidemic is dominated by RSV subtype B, unlike the major RSV summer epidemic in 2021 dominated by RSV subtype A.

COVID-19 mortality attenuated during widespread Omicron transmission, Denmark, 2020 to 2022.

BackgroundIt sparked considerable attention from international media when Denmark lifted restrictions against COVID-19 in February 2022 amidst widespread transmission of the new SARS-CoV-2 Omicron variant and a steep rise in reported COVID-19 mortality based on the 30-day COVID-19 death count.AimOur aim was to investigate how coincidental infections affected COVID-19 mortality estimates following the introduction of the Omicron variant in late 2021.MethodsWe compared the 30-day COVID-19 death count with the observed mortality using three alternative mortality estimation methods; (i) a mathematical model to correct the 30-day COVID-19 death count for coincidental deaths, (ii) the Causes of Death Registry (CDR) and (iii) all-cause excess mortality.ResultsThere was a substantial peak in the 30-day COVID-19 death count following the emergence of the Omicron variant in late 2021. However, there was also a substantial change in the proportion of coincidental deaths, increasing from 10-20% to around 40% of the recorded COVID-19 deaths. The high number of 30-day COVID-19 deaths was not reflected in the number of COVID-19 deaths in the CDR and the all-cause excess mortality surveillance.ConclusionOur analysis showed a distinct change in the mortality pattern following the introduction of Omicron in late 2021 with a markedly higher proportion of people estimated to have died with, rather than of, COVID-19 compared with mortality patterns observed earlier in the COVID-19 pandemic. Our findings highlight the importance of incorporating alternative mortality surveillance methods to more correctly estimate the burden of COVID-19 as the pandemic continues to evolve.

Severe Human Case of Zoonotic Infection with Swine-Origin Influenza A Virus, Denmark, 2021.

During routine surveillance at the National Influenza Center, Denmark, we detected a zoonotic swine influenza A virus in a patient who became severely ill. We describe the clinical picture and the genetic characterization of this variant virus, which is distinct from another variant found previously in Denmark.

Potential role of transthoracic echocardiography for screening LV systolic dysfunction in patients with a history of dengue infection. A cross-sectional and cohort study and review of the literature.

BACKGROUND: Dengue virus can affect the cardiovascular system and men may be at higher risk of severe complications than women. We hypothesized that clinical dengue virus (DENV) infection could induce myocardial alterations of the left ventricle (LV) and that these changes could be detected by transthoracic echocardiography. METHODOLOGY/PRINCIPAL FINDINGS: We examined individuals from Acre in the Amazon Basin of Brazil in 2020 as part of the Malaria Heart Study. By questionnaires we collected information on self-reported prior dengue infection. All individuals underwent transthoracic echocardiography, analysis of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). We included 521 persons (mean age 40±15 years, 39% men, 50% urban areas) of which 253 (49%) had a history of dengue infection. In multivariable models adjusted for clinical and sociodemographic data, a history of self-reported dengue was significantly associated with lower LVEF (ß = -2.37, P < 0.01) and lower GLS (ß = 1.08, P < 0.01) in men, whereas no significant associations were found in women (P > 0.05). In line with these findings, men with a history of dengue had higher rates of LV systolic dysfunction (LVEF < 50% = 20%; GLS < 16% = 17%) than those without a history of dengue (LVEF < 50% = 7%; GLS < 16% = 8%; P < 0.01 and 0.06, respectively). CONCLUSIONS/SIGNIFICANCE: The findings of this study suggest that a clinical infection by dengue virus could induce myocardial alterations, mainly in men and in the LV, which could be detected by conventional transthoracic echocardiography. Hence, these results highlight a potential role of echocardiography for screening LV dysfunction in participants with a history of dengue infection. Further larger studies are warranted to validate the findings of this study.

Excess all-cause mortality in the USA and Europe during the COVID-19 pandemic, 2020 and 2021.

Both the USA and Europe experienced substantial excess mortality in 2020 and 2021 related to the COVID-19 pandemic. Methods used to estimate excess mortality vary, making comparisons difficult. This retrospective observational study included data on deaths from all causes occurring in the USA and 25 European countries or subnational areas participating in the network for European monitoring of excess mortality for public health action (EuroMOMO). We applied the EuroMOMO algorithm to estimate excess all-cause mortality in the USA and Europe during the first two years of the COVID-19 pandemic, 2020-2021, and compared excess mortality by age group and time periods reflecting three primary waves. During 2020-2021, the USA experienced 154.5 (95% Uncertainty Interval [UI]: 154.2-154.9) cumulative age-standardized excess all-cause deaths per 100,000 person years, compared with 110.4 (95% UI: 109.9-111.0) for the European countries. Excess all-cause mortality in the USA was higher than in Europe for nearly all age groups, with an additional 44.1 excess deaths per 100,000 person years overall from 2020-2021. If the USA had experienced an excess mortality rate similar to Europe, there would have been approximately 391 thousand (36%) fewer excess deaths in the USA.

A late sharp increase in influenza detections and low interim vaccine effectiveness against the circulating A(H3N2) strain, Denmark, 2021/22 influenza season up to 25 March 2022.

We estimated interim influenza A vaccine effectiveness (VE) following a late sharp rise in cases during an influenza A(H3N2)-dominated 2021/22 season, after lifting COVID-19 restrictions. In children aged 2-6 years offered a live attenuated influenza vaccine, adjusted VE was 62.7% (95% CI: 10.9-84.4) in hospitalised and 64.2% (95% CI: 50.5-74.1) in non-hospitalised children. In non-hospitalised patients aged 7-44 years, VE was 24.8% (95% CI: 12.8-35.2); VE was non-significant in remaining age groups and hospital/non-hospital settings.

Prevalence and Dynamic Changes in Lung Ultrasound Findings among Adults with Uncomplicated Malaria and Controls in the Amazon Basin, Brazil.

Malaria patients are at risk of cardiopulmonary complications but diagnosis and management can be difficult in resource-limited settings. B-lines on lung ultrasound (LUS) mark changes in lung density; however, little is known about their role in malaria. We aimed to examine the prevalence of B-lines in adults with malaria at baseline and follow-up compared with controls in the Amazon Basin. We also examined the relationship between B-lines and left ventricular ejection fraction. We performed eight-zone LUS, echocardiography, and blood smears in 94 adults (mean age 40 years, 54% men) with uncomplicated malaria and 449 controls without heart failure, renal insufficiency or lung disease (mean age 41 years, 38% men). Examinations of adults with malaria were repeated after antimalarial treatment, corresponding to a median of 30 days (interquartile range [IQR] 27-39). Adults with malaria suffered from Plasmodium vivax (N = 70, median 2,823 [IQR 598-7,698] parasites/µL) or P. falciparum (N = 24, median 1,148 [IQR 480-3,128] parasites/µL). At baseline, adults with malaria more frequently had ≥ 3 B-lines (summed across eight zones) compared with controls (30% versus 2%, P value < 0.001), indicating higher lung density. When examinations were repeated, only 6% of adults with malaria had ≥ 3 B-lines at follow-up, which was significant lower compared with baseline (median reduction 3 B-line; P value < 0.001). B-lines were not significantly associated with left ventricular ejection fraction in adults with malaria. In conclusion, B-lines detected by LUS were more frequent in adults with uncomplicated malaria compared with controls and decreased after completed antimalarial treatment.

All-cause versus cause-specific excess deaths for estimating influenza-associated mortality in Denmark, Spain, and the United States.

BACKGROUND: Seasonal influenza-associated excess mortality estimates can be timely and provide useful information on the severity of an epidemic. This methodology can be leveraged during an emergency response or pandemic. METHOD: For Denmark, Spain, and the United States, we estimated age-stratified excess mortality for (i) all-cause, (ii) respiratory and circulatory, (iii) circulatory, (iv) respiratory, and (v) pneumonia, and influenza causes of death for the 2015/2016 and 2016/2017 influenza seasons. We quantified differences between the countries and seasonal excess mortality estimates and the death categories. We used a time-series linear regression model accounting for time and seasonal trends using mortality data from 2010 through 2017. RESULTS: The respective periods of weekly excess mortality for all-cause and cause-specific deaths were similar in their chronological patterns. Seasonal all-cause excess mortality rates for the 2015/2016 and 2016/2017 influenza seasons were 4.7 (3.3-6.1) and 14.3 (13.0-15.6) per 100,000 population, for the United States; 20.3 (15.8-25.0) and 24.0 (19.3-28.7) per 100,000 population for Denmark; and 22.9 (18.9-26.9) and 52.9 (49.1-56.8) per 100,000 population for Spain. Seasonal respiratory and circulatory excess mortality estimates were two to three times lower than the all-cause estimates. DISCUSSION: We observed fewer influenza-associated deaths when we examined cause-specific death categories compared with all-cause deaths and observed the same trends in peaks in deaths with all death causes. Because all-cause deaths are more available, these models can be used to monitor virus activity in near real time. This approach may contribute to the development of timely mortality monitoring systems during public health emergencies.

Frequency of Electrocardiographic Alterations and Pericardial Effusion in Patients With Uncomplicated Malaria.

Studies have proposed that malaria may lead to electrocardiographic (ECG) changes and pericardial inflammation. We aimed to investigate the frequency of ECG alterations, determined by ECG and Holter monitoring, and pericardial effusion in patients with malaria infection. We performed a prospective observational study of adult patients with uncomplicated malaria in Amazonas, Brazil. Peripheral blood smears, ECG, and bedside echocardiography were conducted before antimalarial treatment and repeated at follow-up after completed treatment. We evaluated the diagnostic value of PR-segment depression, PR-segment elevation, and Spodick's sign for detecting pericardial effusion. A subset of patients underwent Holter monitoring at baseline. Among 98 cases of uncomplicated malaria (55% men; mean age 40 years; median parasite density 1,774/µl), 75 had Plasmodium vivax, 22 Plasmodium falciparum, and 1 had mixed infection. At baseline, 17% (n = 17) had PR-segment depression, 12% (n = 12) PR-segment elevation, 3% (n = 2) Spodick's sign, and the prevalence of pericardial effusion was 9% (n = 9). ECG alterations had sensitivities of 22% to 89% and specificities of 88% to 100% for detecting pericardial effusion at baseline. PR-segment depression had the best accuracy (sensitivity 89%, specificity 90%). Of the 25 patients, 4 patients who did not have pericardial effusion, displayed nonsustained ventricular tachycardia, determined by Holter monitoring (median duration 43 hours). Follow-up examination data were obtained for 71 patients (median 31 days), for whom PR-segment depression, elevation, and pericardial effusion had reduced significantly (p <0.05). In conclusion, our findings suggest that ECG alterations may be useful to detect pericardial effusion in malaria and that these findings decrease after completed antimalarial treatment.

Reassortant Influenza A(H1N1)pdm09 Virus in Elderly Woman, Denmark, January 2021.

A case of human infection with influenza A(H1N1)pdm09 virus containing a nonstructural gene highly similar to Eurasian avian-like H1Nx swine influenza virus was detected in Denmark in January 2021. We describe the clinical case and report testing results of the genetic and antigenic characterizations of the virus.

Sex-differences in COVID-19 associated excess mortality is not exceptional for the COVID-19 pandemic.

Europe experienced excess mortality from February through June, 2020 due to the COVID-19 pandemic, with more COVID-19-associated deaths in males compared to females. However, a difference in excess mortality among females compared to among males may be a more general phenomenon, and should be investigated in none-COVID-19 situations as well. Based on death counts from Eurostat, separate excess mortalities were estimated for each of the sexes using the EuroMOMO model. Sex-differential excess mortality were expressed as differences in excess mortality incidence rates between the sexes. A general relation between sex-differential and overall excess mortality both during the COVID-19 pandemic and in preceding seasons were investigated. Data from 27 European countries were included, covering the seasons 2016/17 to 2019/20. In periods with increased excess mortality, excess was consistently highest among males. From February through May 2020 male excess mortality was 52.7 (95% PI: 56.29; 49.05) deaths per 100,000 person years higher than for females. Increased male excess mortality compared to female was also observed in the seasons 2016/17 to 2018/19. We found a linear relation between sex-differences in excess mortality and overall excess mortality, i.e., 40 additional deaths among males per 100 excess deaths per 100,000 population. This corresponds to an overall female/male mortality incidence ratio of 0.7. In situations with overall excess mortality, excess mortality increases more for males than females. We suggest that the sex-differences observed during the COVID-19 pandemic reflects a general sex-disparity in excess mortality.

Heart failure associated with imported malaria: a nationwide Danish cohort study.

AIMS: Despite adequate treatment, recent studies have hypothesized that malaria may affect long-term cardiovascular function. We aimed to investigate the long-term risk of cardiovascular events and death in individuals with a history of imported malaria in Denmark. METHODS: Using nationwide Danish registries, we followed individuals with a history of malaria for the risk of incident heart failure (HF), myocardial infarction (MI), cardiovascular death and all-cause death (1 January 1994 to 1 January 2017). The population was age- and sex-matched with individuals without a history of malaria from the Danish population (ratio 1:9). We excluded patients with known HF and ischaemic heart disease at inclusion. RESULTS: We identified 3912 cases with a history of malaria (mean age 33 ± 17 years, 57% male, 41% Plasmodium falciparum infections). The median follow-up was 9.8 years (interquartile range 3.9-16.4 years). Event rates per 1000 person-years for individuals with a history vs. no history of malaria were HF: 1.84 vs. 1.32; MI: 1.28 vs. 1.30; cardiovascular death: 1.40 vs. 1.77; and all-cause death: 5.04 vs. 5.28. In Cox proportional hazards models adjusted for cardiovascular risk factors, concomitant pharmacotherapy, region of origin, household income and educational level, malaria was associated with HF (HR: 1.59 [1.21-2.09], P = 0.001), but not MI (HR: 1.00 [0.72-1.39], P = 1.00), cardiovascular death (HR: 1.00 [0.74-1.35], P = 0.98) or all-cause death (HR 1.11 [0.94-1.30], P = 0.21). Specifically, P. falciparum infection was associated with increased risk of HF (HR: 1.64 [1.14-2.36], P = 0.008). CONCLUSION: Individuals with a history of imported malaria, specifically P. falciparum, may have an increased risk of incident HF.

Cardiopulmonary alterations by ultrasound in a patient with uncomplicated mixed malaria infection: a case report from the Amazon Basin.

BACKGROUND: Information on cardiopulmonary complications in clinical malaria is sparse and diagnosis may be difficult in resource-limited areas due to lack of proper diagnostic tools and access to medical care. A case of pericardial effusion and pulmonary alterations assessed by ultrasound in a patient with uncomplicated mixed malaria infection is described. CASE PRESENTATION: A previously healthy 23-year-old male from the Amazon Basin was diagnosed with mixed infection of Plasmodium vivax and Plasmodium falciparum by peripheral blood smear. The patient presented with mild malaria symptoms without signs of severe malaria, but reported moderate chest pain and shortness of breath. Laboratory analyses revealed thrombocytopenia and anemia. The electrocardiogram had PR depressions and bedside ultrasound of the cardiopulmonary system showed pericardial effusion (18 mm) accompanied by multiple B-lines in the lungs, identified as vertical artifacts extending from the pleural line. Cardiac biomarkers were normal. The patient was treated according to national guidelines for malaria and suspected pericarditis, respectively. At follow-up on day 5, the pericardial effusion (9mm) and B-lines had markedly decreased. By day 21 the patient was asymptomatic, had completed the treatment, and the electrocardiogram and ultrasound findings had normalized. CONCLUSIONS: This case report highlight the usefulness of bedside ultrasound to identify cardiopulmonary involvement in patients with uncomplicated malaria and relevant symptoms.

Abrupt termination of the 2019/20 influenza season following preventive measures against COVID-19 in Denmark, Norway and Sweden.

BackgroundIn mid-March 2020, a range of public health and social measures (PHSM) against the then new coronavirus disease (COVID-19) were implemented in Denmark, Norway and Sweden.AimWe analysed the development of influenza cases during the implementation of PHSM against SARS-CoV-2 in the Scandinavian countries.MethodBased on the established national laboratory surveillance of influenza, we compared the number of human influenza cases in the weeks immediately before and after the implementation of SARS-CoV-2 PHSM by country. The 2019/20 influenza season was compared with the five previous seasons.ResultsA dramatic reduction in influenza cases was seen in all three countries, with only a 3- to 6-week duration from the peak of weekly influenza cases until the percentage dropped below 1%. In contrast, in the previous nine influenza seasons, the decline from the seasonal peak to below 1% of influenza-positive samples took more than 10 weeks.ConclusionsThe PHSM against SARS-CoV-2 were followed by a dramatic reduction in influenza cases, indicating a wider public health effect of the implemented measures.

Prevalence of Cardiovascular Complications in Malaria: A Systematic Review and Meta-Analysis.

Recent studies have suggested that malaria may affect the cardiovascular system. The aim of this systematic review and meta-analysis was to determine the prevalence of cardiovascular complications in symptomatic malaria patients. We searched databases such as Pubmed, Embase, Cochrane, and Web of Science (January 1950-April 2020) for studies reporting on cardiovascular complications in adults and children with malaria. Cardiovascular complications were defined as abnormalities in electrocardiogram (ECG), cardiac biomarkers, and echocardiography on admission or during outpatient examination. Studies of patients with known heart disease or cardiovascular evaluation performed after the start of intravenous antimalarial medication were excluded. The study was registered in International Prospective Register of Systematic Reviews (PROSPERO) (No.: CRD42020167672). The literature search yielded 1,243 studies, and a total of 43 studies with symptomatic malaria patients were included. Clinical studies (n = 12 adults; n = 5 children) comprised 3,117 patients, of which a majority had Plasmodium falciparum (n = 15) and were diagnosed with severe malaria (n = 13). In random-effects models of adults, the pooled prevalence estimate for any cardiovascular complication was 7% (95% CI: 5-9). No meta-analysis was conducted in children, but the range of abnormal ECG was 0-8%, cardiac biomarkers 0-57%, and echocardiography 4-9%. We analyzed 33 cases (n = 10 postmortem), in which the most common cardiovascular pathologies were myocarditis and acute coronary syndrome. All histopathological studies found evidence of parasitized red blood cells in the myocardium. Cardiovascular complications are not uncommon in symptomatic adults and children with malaria. Additional studies investigating malaria and cardiovascular disease are encouraged.

Estimates of mortality attributable to COVID-19: a statistical model for monitoring COVID-19 and seasonal influenza, Denmark, spring 2020.

BackgroundTimely monitoring of COVID-19 impact on mortality is critical for rapid risk assessment and public health action.AimBuilding upon well-established models to estimate influenza-related mortality, we propose a new statistical Attributable Mortality Model (AttMOMO), which estimates mortality attributable to one or more pathogens simultaneously (e.g. SARS-CoV-2 and seasonal influenza viruses), while adjusting for seasonality and excess temperatures.MethodsData from Nationwide Danish registers from 2014-week(W)W27 to 2020-W22 were used to exemplify utilities of the model, and to estimate COVID-19 and influenza attributable mortality from 2019-W40 to 2020-W20.ResultsSARS-CoV-2 was registered in Denmark from 2020-W09. Mortality attributable to COVID-19 in Denmark increased steeply, and peaked in 2020-W14. As preventive measures and national lockdown were implemented from 2020-W12, the attributable mortality started declining within a few weeks. Mortality attributable to COVID-19 from 2020-W09 to 2020-W20 was estimated to 16.2 (95% confidence interval (CI): 12.0 to 20.4) per 100,000 person-years. The 2019/20 influenza season was mild with few deaths attributable to influenza, 3.2 (95% CI: 1.1 to 5.4) per 100,000 person-years.ConclusionAttMOMO estimates mortality attributable to several pathogens simultaneously, providing a fuller picture of mortality by COVID-19 during the pandemic in the context of other seasonal diseases and mortality patterns. Using Danish data, we show that the model accurately estimates mortality attributable to COVID-19 and influenza, respectively. We propose using standardised indicators for pathogen circulation in the population, to make estimates comparable between countries and applicable for timely monitoring.

Real-time monitoring shows substantial excess all-cause mortality during second wave of COVID-19 in Europe, October to December 2020.

The European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.