Incidence of Legionnaires' Disease among Travelers Visiting Hotels in Germany, 2015-2019.

We determined whether the incidence rates of travel-associated Legionnaires' disease (TALD) in hotels in Germany increased after a previous occurrence and whether control measures required by the European Legionnaires' Disease Surveillance Network after a cluster (>2 cases within 2 years) restored the rate to baseline. We analyzed TALD surveillance data from Germany during 2015-2019; a total of 307 TALD cases (163 domestic, 144 nondomestic) in hotels were reported. The incidence rate ratio was 5.5 (95% CI 3.6-7.9) for a second case and 25 (95% CI 11-50) for a third case after a cluster had occurred, suggesting that control measures initiated after the occurrence of TALD clusters might be inadequate to restore the incidence rate to baseline. Our findings indicate that substantial LD preventive measures should be explored by hotels or other accommodations after the first TALD case occurs to reduce the risk for future infections.

Bus Riding as Amplification Mechanism for SARS-CoV-2 Transmission, Germany, 20211.

To examine the risk associated with bus riding and identify transmission chains, we investigated a COVID-19 outbreak in Germany in 2021 that involved index case-patients among bus-riding students. We used routine surveillance data, performed laboratory analyses, interviewed case-patients, and conducted a cohort study. We identified 191 case-patients, 65 (34%) of whom were elementary schoolchildren. A phylogenetically unique strain and epidemiologic analyses provided a link between air travelers and cases among bus company staff, schoolchildren, other bus passengers, and their respective household members. The attack rate among bus-riding children at 1 school was ≈4 times higher than among children not taking a bus to that school. The outbreak exemplifies how an airborne agent may be transmitted effectively through (multiple) short (<20 minutes) public transport journeys and may rapidly affect many persons.

How valid is the 2- to 10-day incubation period for cases of Legionnaires' disease?: A reappraisal in the context of the German LeTriWa study; Berlin, 2016-2020.

The evidence for the incubation period of Legionnaires' disease is based on data from a small number of outbreaks. An incubation period of 2-10 days is commonly used for the definition and investigation of cases. In the German LeTriWa study, we collaborated with public health departments to identify evidence-based sources of exposure among cases of Legionnaires' disease within 1-14 days before symptom onset. For each individual, we assigned weights to the numbered days of exposure before symptom onset, giving the highest weight to exposure days of cases with only one possible day of exposure. We then calculated an incubation period distribution where the median was 5 days and the mode was 6 days. The cumulative distribution reached 89% by the 10th day before symptom onset. One case-patient with immunosuppression had a single day of exposure to the likely infection source only 1 day before symptom onset. Overall, our results support the 2- to 10-day incubation period used in case definition, investigation, and surveillance of cases with Legionnaires' disease.

Transmission of SARS-CoV-2 among children and staff in German daycare centres.

In daycare centres, the close contact of children with other children and employees favours the transmission of infections. The majority of children <6 years attend daycare programmes in Germany, but the role of daycare centres in the SARS-CoV-2 pandemic is unclear. We investigated the transmission risk in daycare centres and the spread of SARS-CoV-2 to associated households. 30 daycare groups with at least one recent laboratory-confirmed SARS-CoV-2 case were enrolled in the study (10/2020-06/2021). Close contact persons within daycare and households were examined over a 12-day period (repeated SARS-CoV-2 PCR tests, genetic sequencing of viruses, symptom diary). Households were interviewed to gain comprehensive information on each outbreak. We determined primary cases for all daycare groups. The number of secondary cases varied considerably between daycare groups. The pooled secondary attack rate (SAR) across all 30 daycare centres was 9.6%. The SAR tended to be higher when the Alpha variant was detected (15.9% vs. 5.1% with evidence of wild type). The household SAR was 53.3%. Exposed daycare children were less likely to get infected with SARS-CoV-2 than employees (7.7% vs. 15.5%). Containment measures in daycare programmes are critical to reduce SARS-CoV-2 transmission, especially to avoid spread to associated households.

COVID-19 infections in day care centres in Germany: social and organisational determinants of infections in children and staff in the second and third wave of the pandemic.

BACKGROUND: During the SARS-CoV-2 pandemic, German early childhood education and care (ECEC) centres organised children's attendance in different ways, they reduced opening hours, provided emergency support for a few children, or closed completely. Further, protection and hygiene measures like fixed children-staff groups, ventilation and surface disinfection were introduced in ECEC centres. To inform or modify public health measures in ECEC, we investigate the occurrence of SARS-CoV-2 infections among children and staff in ECEC centres in light of social determinants (i.e. the socioeconomic status of the children) and recommended structural and hygiene measures. We focus on the question if the relevant factors differ between the 2nd (when no variant of concern (VOC) circulated) and the 3rd wave (when VOC B.1.1.7 (Alpha) predominated). METHODS: Based on panel data from a weekly online survey of ECEC centre managers (calendar week 36/2020 to 22/2021, ongoing) including approx. 8500 centres, we estimate the number of SARS-CoV-2 infections in children and staff using random-effect-within-between (REWB) panel models for count data in the 2nd and 3rd wave. RESULTS: ECEC centres with a high proportion of children with low socioeconomic status (SES) have a higher risk of infections in staff and children. Strict contact restrictions between groups like fixed group assignments for children and fixed staff assignments to groups prevent infections. Both effects tend to be stronger in the 3rd wave. CONCLUSION: ECEC centres with a large proportion of children with a low SES background and lack of using fixed child/staff cohorts experience higher COVID-19 rates. Over the long run, centres should be supported in maintaining recommended measures. Preventive measures such as the vaccination of staff should be prioritised in centres with large proportions of low SES children.

Delta and Omicron: protective measures and SARS-CoV-2 infections in day care centres in Germany in the 4th and 5th wave of the pandemic 2021/2022.

BACKGROUND: During the five waves of the SARS-CoV-2 pandemic so far, German early childhood education and care (ECEC) centres implemented various protective measures, such as wearing a face mask, fixed children-staff groups or regular ventilation. In addition, parents and ECEC staff were increasingly vaccinated throughout 2021. During the 4th wave, variant of concern (VOC) Delta-driven transmission indicators reached record values at the end of 2021. Those values were even exceeded in the 5th wave at the beginning of 2022 when Omicron dominated. We examine which factors facilitated or prevented infection with SARS-CoV-2 in ECEC centres, and if these differed between different phases within wave 4 (Delta) and 5 (Omicron). METHODS: Since August 2020, a weekly online survey among approximately 8000 ECEC managers has been conducted, monitoring both incident SARS-CoV-2 infections and protective measures taken. We included data from calendar week 26/2021 to 05/2022. We estimate the probability of any infections and the number of SARS-CoV-2 infections in children, parents and staff using random-effect-within-between (REWB) panel models for binomial and count data. RESULTS: While children, parents and staff of ECEC centres with a high proportion of children from families with low socioeconomic status (SES) have a higher risk of infections in the beginning of wave 4 (OR up to 1.99 [1.56; 2.56]), this effect diminishes for children and parents with rising incidences. Protective measures, such as wearing face masks, tend to have more extensive effects with rising incidences in wave 5 (IRR up to 0.87 [0.8; 0.93]). Further, the protective effect of vaccination against infection among staff is decreasing from wave 4 to wave 5 (OR 0.3 [0.16; 0.55] to OR 0.95, [0.84; 1.07, n.s.]). The degree of transmission from staff to child and from staff to parent is decreasing from wave 4 to wave 5, while transmission from child to staff seems to increase. CONCLUSION: While Omicron seems to affect children and parents from ECEC centres with families with all SES levels more equally than Delta, the protective effect of vaccination against infection is decreasing and the effect of protective measures like face masks becomes increasingly important. In order to prevent massive closures of ECEC centres due to infection of staff, protective measures should be strictly adhered to, especially to protect staff in centres with a high proportion of children from families with low socioeconomic status.

Analysis of Asymptomatic and Presymptomatic Transmission in SARS-CoV-2 Outbreak, Germany, 2020.

We determined secondary attack rates (SAR) among close contacts of 59 asymptomatic and symptomatic coronavirus disease case-patients by presymptomatic and symptomatic exposure. We observed no transmission from asymptomatic case-patients and highest SAR through presymptomatic exposure. Rapid quarantine of close contacts with or without symptoms is needed to prevent presymptomatic transmission.

Factors preventing SARS-CoV-2 transmission during unintentional exposure in a GP practice: a cohort study of patient contacts; Germany, 2020.

Two general practitioners (GPs) with SARS-CoV-2 infection provided in-person patient care to patients of their joint medical practice before and after symptom onset, up until SARS-CoV-2 laboratory confirmation. Through active contact tracing, the local public health authorities recruited the cohort of patients that had contact with either GP in their putative infectious period. In this cohort of patient contacts, we assess the frequency and determinants of SARS-CoV-2-transmission from GPs to patients. We calculated incidence rate ratios (IRR) to explore the type of contact as an explanatory variable for COVID-19 cases. Among the cohort of 83 patient contacts, we identified 22 (27%) COVID-19 cases including 17 (21%) possible, three (4%) probable and two (2%) confirmed cases. All 22 cases had contact with a GP when the GP did not wear a mask, and/or when contact was ≥10 min. Importantly, patients who had contact <10 min with a GP wearing a facemask were at reduced risk (IRR 0.21; 95% CI 0.01-0.99) of COVID-19. This outbreak investigation adds to the body of evidence in supporting current guidelines on measures at preventing the transmission of SARS-CoV-2 in an outpatient setting.

SARS-CoV-2 variant B.1.1.7 susceptibility and infectiousness of children and adults deduced from investigations of childcare centre outbreaks, Germany, 2021.

We investigated three SARS-CoV-2 variant B.1.1.7 childcare centre and related household outbreaks. Despite group cohorting, cases occurred in almost all groups, i.e. also among persons without close contact. Children's secondary attack rates (SAR) were similar to adults (childcare centres: 23% vs 30%; p = 0.15; households: 32% vs 39%; p = 0.27); child- and adult-induced household outbreaks also led to similar SAR. With the advent of B.1.1.7, susceptibility and infectiousness of children and adults seem to converge. Public health measures should be revisited accordingly.

[Field investigations of SARS-CoV-2-outbreaks in Germany by the Robert Koch Institute, February-October 2020]. / Untersuchung von SARS-CoV-2-Ausbrüchen in Deutschland durch Feldteams des Robert Koch-Instituts, Februar­Oktober 2020.

The Robert Koch Institute (RKI) offers advice and assistance to local public health agencies on the investigation and management of outbreaks of infectious diseases. Specially trained experts conduct field investigations. During the COVID-19 pandemic, RKI experts participated in the investigation of outbreaks in residential buildings, physicians' offices, nursing homes, hospitals, and asylum seekers' facilities as well as at a night club and on a cruise ship.This report describes some of the field investigations conducted in Germany during the COVID-19 pandemic between February and October 2020. The investigations provided information on the properties of SARS-CoV­2 and its transmission as a basis for the recommendations on suitable prevention measures. The practical examples demonstrate the variety of support given as well as the opportunities to gather epidemiological evidence.In September 2020, the RKI established a new unit called the "Focal Point for the Public Health Service," which now coordinates and is expanding field support. In order to further support the public health system to improve its capability to react to and investigate outbreaks of infectious diseases, interdisciplinary training shall be intensified.

[SARS-CoV-2 incidence, transmission, and containment measures in daycare centers during the COVID-19 pandemic-findings from the Corona Daycare Study]. / Infektionsgeschehen und Eindämmungsmaßnahmen in Kitas während der COVID-19-Pandemie ­ Erkenntnisse aus der Corona-KiTa-Studie.

BACKGROUND: Daycare centers are of substantial sociopolitical and pedagogical relevance; at the same time, the close contact of children in daycare groups among each other and with employees favors the transmission of infections. In the COVID-19 pandemic, questions arose about how infection events occur in daycare centers, what role daycare children play in the pandemic, and what protective and hygienic measures are implemented in daycare centers. From 06/2020 to 12/2021, we conducted the "Corona Day Care Study," in which we address pedagogical and infection epidemiological topics in a joint approach. METHODS: In the study, data are collected from different sources. Official reporting data as well as weekly data from daycare centers in the so-called KiTa Register are continuously evaluated. In addition, SARS-CoV­2 outbreaks in daycare centers are investigated on site by repeated sample collection and interviews. RESULTS: SARS-CoV­2 infection incidence in daycare centers or in daycare-aged children was very dynamic from 03/2020 to 05/2021. In the second and third pandemic waves, the number of SARS-CoV­2 outbreaks in daycare centers rose sharply, accompanied by a substantial increase in daycare and group closures. Most recently, the proportion of affected children in outbreaks increased steadily. However, preliminary examinations of SARS-CoV­2 outbreaks (n = 28) revealed that, on average, only a fraction of daycare contact persons (6.8%) were infected by child index cases. Transmission frequencies differed markedly between the individual daycare centers. DISCUSSION: The combination of regularly collected reporting and survey data as well as outbreak investigations allows a multilayered monitoring and understanding of infection events in daycare centers; its findings could be incorporated into recommendations for public health measures.

[Measures to cope with the COVID-19 pandemic in Germany: nonpharmaceutical and pharmaceutical interventions]. / Maßnahmen zur Bewältigung der COVID-19-Pandemie in Deutschland: nichtpharmakologische und pharmakologische Ansätze.

When the emerging novel SARS-CoV­2 virus first appeared in December 2019, neither specific therapeutic options nor vaccinations were available. The role of nonpharmaceutical interventions (NPIs) became of central importance. At the Robert Koch Institute, a multilayer strategy consisting of population-based and individual preventive measures to control the pandemic was developed, which built upon existing influenza pandemic plans as well as generic plans. This paper explains the recommended NPIs and illustrates the pharmaceutical approaches developed in parallel.Among others, general contact bans, providing material for infection prevention and control, ban of events, closing educational institutions, and restricting travel are counted among population-based measures. Additional individual preventive measures are necessary, e.g., keeping a minimum distance, reducing contacts, and wearing a mouth-nose covering as well as quarantine and isolation. Measures within the health system are based on recommendations of the Commission on Hospital Hygiene and Infection Protection (Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO)) and specified and implemented by professional societies. Since November 2020, an antiviral therapy with remdesivir and treatment with the glucocorticoid dexamethasone have been available as pharmaceutical interventions. Monoclonal antibodies are at this time not approved. Therapeutic anticoagulation is recommended.Recommendations are constantly adapted to the increasing knowledge on the pathogen and its means of transmission. A challenge is to strengthen the trust of the population. Many measures have to be applied on an individual basis in order to work together.

[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.

Surveillance of COVID-19 school outbreaks, Germany, March to August 2020.

Mitigation of the coronavirus disease (COVID-19) pandemic in Germany included school closures in early March 2020. After reopening in April, preventive measures were taken in schools. We analysed national surveillance system data on COVID-19 school outbreaks during different time periods. After reopening, smaller outbreaks (average: 2.2/week) occurred despite low incidence in the general population. School closures might have a detrimental effect on children and should be applied only cautiously and in combination with other measures.

Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.

BACKGROUND: Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015. METHODS: We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65-74 years, and ≥75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. FINDINGS: EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100 000 individuals for people younger than 65 years, 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100 000 for people older than 75 years. We estimated that 291 243-645 832 seasonal influenza-associated respiratory deaths (4·0-8·8 per 100 000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2·8-16·5 per 100 000 individuals), southeast Asia (3·5-9·2 per 100 000 individuals), and among people aged 75 years or older (51·3-99·4 per 100 000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243-105 690 influenza-associated respiratory deaths occur annually. INTERPRETATION: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated. FUNDING: None.

[Estimation of heat-related deaths in Germany between 2001 and 2015]. / Schätzung hitzebedingter Todesfälle in Deutschland zwischen 2001 und 2015.

BACKGROUND: During the summers of 2003 and 2015, heat was found to be the cause of a substantial number of deaths in Germany. Until now, estimates for the total number of heat-related deaths were only available regionally in Germany. For the summer of 2003, an analysis for Baden-Württemberg was extrapolated to the whole of Germany. OBJECTIVES: Our analysis tries to prove a stable statistical relationship between heat and mortality and to use this to quantify the number of heat-related deaths in Germany between the years 2001 and 2015. MATERIALS AND METHODS: By fitting a nonlinear statistical model, we estimated exposure-response curves that describe the influence of heat on the mortality rate. The performance of different indicators for heat stress was compared. RESULTS: The comparison of the different indicators for heat showed that the weekly mean temperature was most useful to explain the course of the weekly mortality during the summer. The relation between mortality rate and weekly mean temperature varied between age groups and regions in Germany (north, middle, south). The age groups (75-84) and (85+) were most affected by heat. The highest number of heat-related deaths was 7600 (95% CI 5500-9900), found for the summer 2003, followed by 6200 (4000; 8000) in the summer 2006 and 6100 (4000; 8300) in the summer 2015. CONCLUSIONS: We could show that even in weekly data on mortality, a clear influence of heat could be identified. A national surveillance of mortality that allows real-time monitoring would be desirable.

Is the impact of childhood influenza vaccination less than expected: a transmission modelling study.

BACKGROUND: To reduce the burden of severe influenza, most industrialized countries target specific risk-groups with influenza vaccines, e.g. the elderly or individuals with comorbidities. Since children are the main spreaders, some countries have recently implemented childhood vaccination programs to reduce overall virus transmission and thereby influenza disease in the whole population. The introduction of childhood vaccination programs was often supported by modelling studies that predicted substantial incidence reductions. We developed a mathematical transmission model to examine the potential impact of childhood influenza vaccination in Germany, while also challenging established modelling assumptions. METHODS: We developed an age-stratified SEIR-type transmission model to reproduce the epidemic influenza seasons between 2003/04 and 2013/14. The model was built upon German population counts, contact patterns, and vaccination history and was fitted to seasonal data on influenza-attributable medically attended acute respiratory infections (I-MAARI) and strain distribution using Bayesian methods. As novelties we (i) implemented a stratified model structure enabling seasonal variability and (ii) deviated from the commonly assumed mass-action-principle by employing a phenomenological transmission rate. RESULTS: According to the model, by vaccinating primarily the elderly over ten seasons 4 million (95% prediction interval: 3.84 - 4.19) I-MAARI were prevented which corresponds to an 8.6% (8.3% - 8.9%) reduction compared to a no-vaccination scenario and a number-needed-to-vaccinate (NNV) to prevent one I-MAARI of 37.1 (35.5 - 38.7). Additional vaccination of 2-10 year-old children at 40% coverage would have led to an overall I-MAARI reduction of 17.8% (17.1 - 18.7%) mostly due to indirect effects with a NNV of 20.7 (19.6 - 21.6). When employing the traditional mass-action-principle, the model predicted a more than 3-fold higher I-MAARI reduction (55.6%) due to childhood vaccination. CONCLUSION: In Germany, the introduction of routine childhood influenza vaccination could considerably reduce I-MAARI among all age-groups and improve the NNV. However, the predicted impact is much lower compared to previous studies, which is primarily caused by our phenomenological approach to modelling influenza virus transmission.

I-MOVE multicentre case-control study 2010/11 to 2014/15: Is there within-season waning of influenza type/subtype vaccine effectiveness with increasing time since vaccination?

Since the 2008/9 influenza season, the I-MOVE multicentre case-control study measures influenza vaccine effectiveness (VE) against medically-attended influenza-like-illness (ILI) laboratory confirmed as influenza. In 2011/12, European studies reported a decline in VE against influenza A(H3N2) within the season. Using combined I-MOVE data from 2010/11 to 2014/15 we studied the effects of time since vaccination on influenza type/subtype-specific VE. We modelled influenza type/subtype-specific VE by time since vaccination using a restricted cubic spline, controlling for potential confounders (age, sex, time of onset, chronic conditions). Over 10,000 ILI cases were included in each analysis of influenza A(H3N2), A(H1N1)pdm09 and B; with 4,759, 3,152 and 3,617 influenza positive cases respectively. VE against influenza A(H3N2) reached 50.6% (95% CI: 30.0-65.1) 38 days after vaccination, declined to 0% (95% CI: -18.1-15.2) from 111 days onwards. At day 54 VE against influenza A(H1N1)pdm09 reached 55.3% (95% CI: 37.9-67.9) and remained between this value and 50.3% (95% CI: 34.8-62.1) until season end. VE against influenza B declined from 70.7% (95% CI: 51.3-82.4) 44 days after vaccination to 21.4% (95% CI: -57.4-60.8) at season end. To assess if vaccination campaign strategies need revising more evidence on VE by time since vaccination is urgently needed.