Atypical age distribution and high disease severity in children with RSV infections during two irregular epidemic seasons throughout the COVID-19 pandemic, Germany, 2021 to 2023.

BackgroundNon-pharmaceutical interventions (NPIs) during the COVID-19 pandemic affected respiratory syncytial virus (RSV) circulation worldwide.AimTo describe, for children aged < 5 years, the 2021 and 2022/23 RSV seasons in Germany.MethodsThrough data and 16,754 specimens from outpatient sentinel surveillance, we investigated RSV seasonality, circulating lineages, and affected children's age distributions in 2021 and 2022/23. Available information about disease severity from hospital surveillance was analysed for patients with RSV-specific diagnosis codes (n = 13,104). Differences between RSV seasons were assessed by chi-squared test and age distributions trends by Mann-Kendall test.ResultsRSV seasonality was irregular in 2021 (weeks 35-50) and 2022/23 (weeks 41-3) compared to pre-COVID-19 2011/12-2019/20 seasons (median weeks 51-12). RSV positivity rates (RSV-PR) were higher in 2021 (40% (522/1,291); p < 0.001) and 2022/23 (30% (299/990); p = 0.005) than in prior seasons (26% (1,430/5,511)). Known globally circulating RSV-A (lineages GA2.3.5 and GA2.3.6b) and RSV-B (lineage GB5.0.5a) strains, respectively, dominated in 2021 and 2022/23. In 2021, RSV-PRs were similar in 1 - < 2, 2 - < 3, 3 - < 4, and 4 - < 5-year-olds. RSV hospitalisation incidence in 2021 (1,114/100,000, p < 0.001) and in 2022/23 (1,034/100,000, p < 0.001) was approximately double that of previous seasons' average (2014/15-2019/20: 584/100,000). In 2022/23, proportions of RSV patients admitted to intensive care units rose (8.5% (206/2,413)) relative to pre-COVID-19 seasons (6.8% (551/8,114); p = 0.004), as did those needing ventilator support (6.1% (146/2,413) vs 3.8% (310/8,114); p < 0.001).ConclusionsHigh RSV-infection risk in 2-4-year-olds in 2021 and increased disease severity in 2022/23 possibly result from lower baseline population immunity, after NPIs diminished exposure to RSV.

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Vaccine effectiveness against influenza hospitalisation in adults during the 2022/2023 mixed season of influenza A(H1N1)pdm09, A(H3N2) and B circulation, Europe: VEBIS SARI VE hospital network.

We conducted a multicentre hospital-based test-negative case-control study to measure vaccine effectiveness (VE) against PCR-confirmed influenza in adult patients with severe acute respiratory infection (SARI) during the 2022/2023 influenza season in Europe. Among 5547 SARI patients ≥18 years, 2963 (53%) were vaccinated against influenza. Overall VE against influenza A(H1N1)pdm09 was 11% (95% CI: -23-36); 20% (95% CI: -4-39) against A(H3N2) and 56% (95% CI: 22-75) against B. During the 2022/2023 season, while VE against hospitalisation with influenza B was >55%, it was ≤20% for influenza A subtypes. While influenza vaccination should be a priority for future seasons, improved vaccines against influenza are needed.

Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023.

We conducted a multicentre hospital-based test-negative case-control study to measure the effectiveness of adapted bivalent COVID-19 mRNA vaccines against PCR-confirmed SARS-CoV-2 infection during the Omicron XBB lineage-predominant period in patients aged ≥ 60 years with severe acute respiratory infection from five countries in Europe. Bivalent vaccines provided short-term additional protection compared with those vaccinated > 6 months before the campaign: from 80% (95% CI: 50 to 94) for 14-89 days post-vaccination, 15% (95% CI: -12 to 35) at 90-179 days, and lower to no effect thereafter.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022.

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.

Respiratory infections in children and adolescents in Germany during the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, acute respiratory infections (ARIs) in children were mainly characterised by three pathogens: respiratory syncytial viruses (RSV), influenza viruses and rhinoviruses. The impact of the COVID-19 pandemic and the measures taken in Germany (especially until the end of 2021) on the incidence of ARI in children and adolescents aged 0 to 14 years and the pathogens causing them has not yet been comprehensively analysed. Methods: The evaluation is based on data from population-based, virological and hospital-based surveillance instruments up to the end of 2022. Results: After the onset of the COVID-19 pandemic in early 2020, ARI rates remained almost consistently below prepandemic levels until autumn 2021, with only rhinoviruses continuously continuing to cause ARI. Only when the Omicron variant became predominant in 2022, there were measurable COVID-19 rates at population level in children, although COVID-19 hospitalisation rates remained comparatively low. RSV and influenza waves were initially absent and then occurred 'out of season', but were more severe than usual. Conclusions: While the measures taken were effective in inhibiting the number of respiratory infections for almost 1.5 years, moderately frequent but rather mild COVID-19 cases occurred when measures were lifted. When Omicron emerged in 2022 COVID-19 became moderately frequent but led predominantly to mild illnesses. For RSV and influenza, the measures resulted in changes in their annual timing and intensity.

[The different periods of COVID-19 in Germany: a descriptive analysis from January 2020 to February 2021]. / Die verschiedenen Phasen der COVID-19-Pandemie in Deutschland: Eine deskriptive Analyse von Januar 2020 bis Februar 2021.

The first case of coronavirus SARS-CoV­2 infection in Germany was diagnosed on 27 January 2020. To describe the pandemic course in 2020, we regarded four epidemiologically different periods and used data on COVID-19 cases from the mandatory reporting system as well as hospitalized COVID-19 cases with severe acute respiratory infection from the syndromic hospital surveillance.Period 0 covers weeks 5 to 9 of 2020, where mainly sporadic cases of younger age were observed and few regional outbreaks emerged. In total, 167 cases with mostly mild outcomes were reported. Subsequently, the first COVID-19 wave occurred in period 1 (weeks 10 to 20 of 2020) with a total of 175,013 cases throughout Germany. Increasingly, outbreaks in hospitals and nursing homes were registered. Moreover, elderly cases and severe outcomes were observed more frequently. Period 2 (weeks 21 to 39 of 2020) was an interim period with more mild cases, where many cases were younger and often travel-associated. Additionally, larger trans-regional outbreaks in business settings were reported. Among the 111,790 cases, severe outcomes were less frequent than in period 1. In period 3 (week 40 of 2020 to week 8 of 2021), the second COVID-19 wave started and peaked at the end of 2020. With 2,158,013 reported cases and considerably more severe outcomes in all age groups, the second wave was substantially stronger than the first wave.Irrespective of the different periods, more elderly persons and more men were affected by severe outcomes.

[Monitoring of COVID-19 by extending existing surveillance for acute respiratory infections]. / Überwachung von COVID-19 durch Erweiterung der etablierten Surveillance für Atemwegsinfektionen.

As part of the national influenza pandemic preparedness, surveillance systems have been established in Germany in addition to the mandatory notifications according to the Protection Against Infection Act. The aim of these systems is the description, analysis, and evaluation of the epidemiology of acute respiratory infections (ARIs), the identification of the circulating viruses, and the trend. Since the beginning of the COVID-19 pandemic, the systems have been expanded to enable monitoring of infections with SARS-CoV­2.Three systems are presented: GrippeWeb, the primary care sentinel Arbeitsgemeinschaft Influenza with its electronic reporting module SEEDARE, and the ICD-10-based hospital sentinel ICOSARI. With these systems, ARIs can be monitored at the population, outpatient, and inpatient levels. In combination with the monitoring of mortality, these systems provide important information on the frequency of different stages of disease severity in the population. In order to expand the systems to SARS-CoV­2, only a few adjustments were needed.As the case definitions for ARIs were preserved, historical baselines of the systems can still be used for comparison. All systems are structured in such a way that stable and established reference values are available for calculating weekly proportions and rates.This is an important addition to the mandatory reporting system of infectious diseases in Germany, which depends on the particular testing strategy, the number of tests performed, and on specific case definitions, which are adapted as required.The surveillance systems have proven to be feasible and efficient in the COVID-19 pandemic, even when compared internationally.

Influenza-associated pneumonia as reference to assess seriousness of coronavirus disease (COVID-19).

Information on severity of coronavirus disease (COVID-19) (transmissibility, disease seriousness, impact) is crucial for preparation of healthcare sectors. We present a simple approach to assess disease seriousness, creating a reference cohort of pneumonia patients from sentinel hospitals. First comparisons exposed a higher rate of COVID-19 patients requiring ventilation. There were more case fatalities among COVID-19 patients without comorbidities than in the reference cohort. Hospitals should prepare for high utilisation of ventilation and intensive care resources.

Evaluation of using ICD-10 code data for respiratory syncytial virus surveillance.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection (ALRI) in young children. ICD-10-based syndromic surveillance can transmit data rapidly in a standardized way. OBJECTIVES: We investigated the use of RSV-specific ICD-10 codes for RSV surveillance. METHODS: We performed a retrospective descriptive data analysis based on existing ICD-10-based surveillance systems for ALRI in primary and secondary care and a linked virological surveillance in Germany. We described RSV epidemiology and compared the epidemiological findings based on ICD-10 and virological data. We calculated sensitivity and specificity of RSV-specific ICD-10 codes and in combination with ICD-10 codes for acute respiratory infections (ARI) for the identification of laboratory-confirmed RSV infections. RESULTS: Based on the ICD-10 and virological data, epidemiology of RSV was described, and common findings were found. The RSV-specific ICD-10 codes had poor sensitivity 6% (95%-CI: 3%-12%) and high specificity 99.8% (95%-CI: 99.6%-99.9%). In children <5 years and in RSV seasons, the sensitivities of RSV-specific ICD-10 codes combined with general ALRI ICD-10 codes J18.-, J20.- and with J12.-, J18.-, J20.-, J21.-, J22 were moderate (44%, 95%-CI: 30%-59%). The specificities of both combinations remained high (91%, 95%-CI: 86%-94%; 90%, 95%-CI: 85%-94%). CONCLUSIONS: The use of RSV-specific ICD-10 codes may be a useful indicator to describe RSV epidemiology. However, RSV-specific ICD-10 codes underestimate the number of actual RSV infections. This can be overcome by combining RSV-specific and general ALRI ICD-10 codes. Further investigations are required to validate this approach in other settings.

[Infectious diseases and their ICD coding : What could be improved by the introduction of ICD-11?] / Infektionskrankheiten und ihre Codierung : Was kann sich durch die ICD-11 verbessern?

The revision of the International Classification of Diseases (ICD) could change morbidity and mortality statistics significantly, which also affects the area of infectious diseases. Infectious diseases are classified according to their etiology, affected body system or the life period during which the episode occurs. Specific challenges arise from emerging pathogens and the respective necessary adaptation. For epidemiologic analysis ICD-10 does not always offer enough additional information.ICD provides the basis for international comparison of infectious disease morbidity and mortality statistics, but it is also used to collect data for surveillance and research purposes, e. g. the notification system for infectious diseases, syndromic surveillance systems and the evaluation of data quality by using secondary data sources.ICD-11 offers the chance to better represent epidemiological concepts of infectious diseases by adding more relevant information as affected body system or manifestation. Due to the complexity of coding, ensuring continuity of morbidity and mortality statistics could be challenging.

Trends in herpes zoster epidemiology in Germany based on primary care sentinel surveillance data, 2005-2016.

Herpes zoster (HZ) is caused by reactivation of the varicella-zoster-virus (VZV). Childhood varicella vaccination, as recommended in Germany in 2004, may reduce the risk of HZ in vaccinated children but also virus circulation and thus the booster possibility of latent infected persons. In this context we analyzed age-specific trends in HZ epidemiology in Germany using data on HZ-associated outpatient consultations in participating sentinel sites and HZ-associated cases in all hospitals since 2005. We analyzed two separate time periods that differed in sentinel management and data integrity. For the period 2005-2010, we found a decrease in HZ-associated outpatient consultations in 1- to 4-year-olds (IRR = 0.72, 95%CI 0.63-0.81, p<0.001). For the period 2013-2016, we observed a decrease in HZ-associated outpatient consultations in 10- to 14-year-olds (IRR = 0.85, 95%CI 0.78-0.93, p<0.01). Moreover, we detected an increase in the age groups 20 years and older except for the group 30-39 years. HZ-associated hospitalizations showed similar trends for the second time period (here 2012-2015). The decrease in HZ-associated outpatient consultations and hospitalizations in children started and continued over cohorts eligible for varicella vaccination and could be a result of their reduced HZ-risk. Whether the observed steady increasing HZ incidences for adults are associated with the varicella vaccination in children remains unclear and could not be investigated with our data.

Time trends in incidence and mortality of respiratory diseases of high public health relevance in Germany.

Respiratory diseases are major causes of disease burden and mortality throughout the world. In Germany, alongside acute respiratory infections (ARI), chronic lung diseases - including lung cancer, chronic obstructive pulmonary disease (COPD), and asthma - are of particular socioeconomic importance. ARI incidence rates differ significantly according to age, season and year. They are recorded as weekly consultation rates as reported by selected outpatient and inpatient care facilities. Between 2009 and 2016, the highest incidence rates of severe acute respiratory infection (SARI) were recorded among young children in outpatient (9.4%) and inpatient (0.2%) care. Mortality rates for ARI are also subject to seasonal and annual fluctuations. However, the official statistics on causes of death, which lead to estimates of more than 17,000 annual deaths, provide an inadequate measure of death rates because chronic underlying illnesses are often recorded as the cause of death rather than a more recently acquired acute infection. Therefore, the excess mortality caused by ARI needs to be assessed in the context of influenza outbreaks. Regarding lung cancer, COPD and asthma, the long-term time trends in disease incidence and mortality rates are of particular interest from a health policy perspective. Analyses of data from the official statistics on causes of death for the years 1998 through 2015 show that mortality rates for lung cancer and COPD decreased on average by 1.8% and 1.1% per year respectively, among men, whereas among women they increased by 2.5% (lung cancer) and 2.3% (COPD) annually. Nevertheless, more men than women died of lung cancer or COPD in 2015 in Germany: 29,378 men and 15,881 women died from lung cancer, and 17,300 men and 13,773 women died from COPD. During the same period, the asthma mortality rates decreased on average by 8.3% annually among women and by 11.2% annually among men, and the absolute number of deaths came down to 659 among women and 393 among men. Lung cancer incidence rates have been at similar levels as lung cancer death rates since 1998. No such data are available on time trends in COPD or asthma incidence rates. Coordinated surveillance of respiratory diseases needs to be expanded within the framework of international action plans for disease prevention.

Strong Additional Effect of a Second Varicella Vaccine Dose in Children in Germany, 2009-2014.

OBJECTIVES: Vaccine effectiveness (VE) of 1 and 2 varicella vaccine doses in children aged 1-4 years in Germany was evaluated to determine the additional effect of a second dose recommended at least 4 weeks after the first dose and before the second birthday. STUDY DESIGN: To estimate the VE, the proportion of cases vaccinated was compared with the proportion of the population vaccinated using nationwide sentinel surveillance data from 2009-2014 and health insurance claims data covering the period January 2009-March 2014, respectively. A general linear model was used to estimate the OR of vaccination in the cases and the population and the corresponding CIs to observe the stability of the VE estimates over time, and to assess the incremental effectiveness of a second dose. RESULTS: The overall VE after 1 dose was 86.6% (95% CI: 85.2-87.9), ranging between 94.6% (95% CI: 87.9-97.6) in the first quarter of 2011 and 50.3% (95% CI: 7.3-73.4) in the third quarter of 2013. The overall VE after 2 doses was 97.3% (95% CI: 97.0-97.6), ranging between 99.5% (95% CI: 97.8-99.9) in the second quarter of 2009 and 91.3% (95% CI: 85.7-94.8) in the third quarter of 2013. The incremental VE of 2 doses was 84.6% (95% CI: 81.7-86.9). CONCLUSIONS: The substantially higher VE of 2 varicella vaccine doses compared with 1 dose in young children and the strong additional effect of the second dose support the public health relevance of a 2-dose schedule and the success of the early second vaccine dose.

Laboratory investigations of vaccinated patients with varicella.

BACKGROUND: Accompanying varicella vaccination in children in Germany recommended with one (2004) and two (2009) doses, sentinel surveillance of varicella with a sample (n∼900) of private physicians was established in 2005. Physicians reported monthly aggregated data on all varicella cases and case-based on vaccinated patients, of whom skin lesion samples were laboratory investigated to identify varicella-zoster virus (VZV). We analyzed the impact of vaccination frequency on the number of cases and on laboratory results within the sentinel. METHODS: Swabs were obtained with a Teflon tip and sent together with a case-based questionnaire to the reference laboratory. VZV wild-type and vaccine-type was identified by polymerase chain-reaction (PCR) and pyrosequencing methods. Case-based data and laboratory results were analyzed descriptively. RESULTS: From April 2005 to March 2014, of all monthly reported cases (n=111,456) 4789 were vaccinated and eligible for further analysis. No differences were found between laboratory investigated and not investigated cases (1017 vs. 3772) except that the proportion of cases vaccinated twice was higher in lab-cases (29.4% vs. 16.1%). PCR remained negative in 69.6% (197/283) of breakthrough-cases vaccinated twice, in comparison to 22.7% (147/649) breakthrough-cases vaccinated once. VZV was confirmed in 500 (81) patients with breakthrough varicella after one (two) vaccination(s); identification of VZV wild-type, vaccine-type, or no further differentiation was possible in 485 (72), 5 (6), and 10 (3) cases, respectively. CONCLUSION: Varicella breakthrough disease is rare in Germany and suspected clinical cases require laboratory confirmation. The lower confirmation rate of VZV after two vaccine doses suggests a better protection compared to one dose.

Results from the first 12 months of the national surveillance of healthcare associated outbreaks in Germany, 2011/2012.

BACKGROUND: In August 2011, the German Protection against Infection Act was amended, mandating the reporting of healthcare associated infection (HAI) outbreak notifications by all healthcare workers in Germany via local public health authorities and federal states to the Robert Koch Institute (RKI). OBJECTIVE: To describe the reported HAI-outbreaks and the surveillance system's structure and capabilities. METHODS: Information on each outbreak was collected using standard paper forms and notified to RKI. Notifications were screened daily and regularly analysed. RESULTS: Between November 2011 and November 2012, 1,326 paper forms notified 578 HAI-outbreaks, between 7 and 116 outbreaks per month. The main causative agent was norovirus (n = 414/578; 72%). Among the 108 outbreaks caused by bacteria, the most frequent pathogens were Clostridium difficile (25%) Klebsiella spp. (19%) and Staphylococcus spp. (19%). Multidrug-resistant bacteria were responsible for 54/108 (50%) bacterial outbreaks. Hospitals were affected most frequently (485/578; 84%). Hospital outbreaks due to bacteria were mostly reported from intensive care units (ICUs) (45%), followed by internal medicine wards (16%). CONCLUSION: The mandatory HAI-outbreak surveillance system describes common outbreaks. Pathogens with a particular high potential to cause large or severe outbreaks may be identified, enabling us to further focus research and preventive measures. Increasing the sensitivity and reliability of the data collection further will facilitate identification of outbreaks able to increase in size and severity, and guide specific control measures to interrupt their propagation.

[Salmonella in laying hens: what does voluntary monitoring tell us?]. / Trendbetrachtung von Salmonellen bei Legehennenherden--was sagen uns freiwillige Untersuchungen?

Based on voluntary examinations for Salmonella in laying hen flocks in Germany, it was investigated whether a statistically significant trend in Salmonella prevalence could be observed in the period 2003 to 2007. Furthermore, it was studied whether the implementation of Regulation (EC) No 1168/2006 led to an improvement of the collected data and a change in the Salmonella prevalence in 2008. To compensate for differences in data availability, submitted data were weighted by regional laying hen population size and compared with results from the non-weighted data. Between the years 2003 to 2007 a significant reduction of Salmonella prevalence could be observed. Weighting of data by population size improved trend recognition for routine sampling results. This may point towards a real reduction of Salmonella prevalence in German layer flocks in the years till 2007. The obligatory implementation of the control programme in 2008 led to a remarkable increase of examinations performed and an increased frequency of detection of Salmonella in flocks of laying hens. This tendency was statistically highly significant (p < 0,0042) for the overall dataset as well as for data from targeted sampling and other sampling. Again, after weighting data from routine sampling, a statistically significant (p < 0.05) increase of Salmonella prevalence could be shown. The two dominant serovars in human salmonellosis, namely S. Enteritidis and S. Typhimurium were most frequently observed in German laying hen flocks with S. Enteritidis being much more recurrent than S. Typhimurium. It is obvious from the available data that a good data quality is the prerequisite for a realistic evaluation of the Salmonella situation and that weighting may compensate for some of the bias inherent in the data reporting system.