European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

OBJECTIVES: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. METHODS: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. RESULTS: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. CONCLUSIONS: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.

Crop wild relative populations of Beta vulgaris allow direct mapping of agronomically important genes.

Rapid identification of agronomically important genes is of pivotal interest for crop breeding. One source of such genes are crop wild relative (CWR) populations. Here we used a CWR population of <200 wild beets (B. vulgaris ssp. maritima), sampled in their natural habitat, to identify the sugar beet (Beta vulgaris ssp. vulgaris) resistance gene Rz2 with a modified version of mapping-by-sequencing (MBS). For that, we generated a draft genome sequence of the wild beet. Our results show the importance of preserving CWR in situ and demonstrate the great potential of CWR for rapid discovery of causal genes relevant for crop improvement. The candidate gene for Rz2 was identified by MBS and subsequently corroborated via RNA interference (RNAi). Rz2 encodes a CC-NB-LRR protein. Access to the DNA sequence of Rz2 opens the path to improvement of resistance towards rhizomania not only by marker-assisted breeding but also by genome editing.

Transmission of shiga toxin-producing Escherichia coli O104:H4 at a family party possibly due to contamination by a food handler, Germany 2011.

We investigated a cluster of shiga toxin-producing Escherichia coli (STEC) O104:H4 infections after a family party during a large STEC O104:H4 outbreak in Germany. To identify the vehicle we conducted a retrospective cohort study. Stool samples of party guests, and food and environmental samples from the catering company were tested for STEC. We defined cases as party guests with gastrointestinal symptoms and laboratory-confirmed STEC infection. We found 23 cases among 71 guests. By multivariable analysis consumption of salmon [odds ratio (OR) 15, 95% confidence interval (CI) 2.3-97], herb cream (OR 6.5, 95% CI 1.3-33) and bean salad (OR 6.1, 95% CI 1.4-26) were associated with STEC infection. STEC O104:H4 was detected in samples of bell pepper and salmon. The food handler developed STEC infection. Our results point towards transmission via several food items contaminated by a food handler. We recommend regular education of food handlers emphasizing their role in transmitting infectious diseases.

[Pandemic 2009/10: reflections on the utility of the vaccination actions in Hesse]. / Pandemie 2009/10: Betrachtungen zum Nutzen der Impfaktion in Hessen.

In the state of Hesse (Germany) all vaccinations were administered either by the public health-care (ÖGD) or private health-care facilities and were registered by week and age group. In the following article, the benefit of the vaccination campaign will be looked at in terms of preventable consultations due to acute respiratory tract infections (AK-ARI). AK-ARI were registered with the nation-wide sentinel of the AGI. Scenarios regarding timing and age-specific coverage are modelled. The achieved timing and age distribution was compared to assumed ideal distributions, e. g., having achieved the final coverage 2 weeks before epidemic start or having applied the used vaccine exclusively for the most affected age group 5-14 years. The timing and coverage actually achieved (7% overall) prevented an estimated 1.4% or, respectively, 1.1% of the total consultation excess. With the same amount of vaccine but ideally applied at least 2 weeks -before the begin of the epidemic and exclusively to the age group of the 5- to 14-year olds, an estimated 13.9% or, respectively, 18.2% of the total excess could have been prevented. The simulated scenarios give estimations as to what benefit potentially could have been achieved during the A(H1N1)pdm09 pandemic. Both the delayed successive access to vaccine and the not ideal age distribution reduced the benefit to about 30% of the optimum. These exemplary estimates underline the importance of timeliness and valid prioritising of vaccination campaigns, although footing on just one outcome. It appears beneficial to reduce uncertainties for a solid prioritisation by, e. g., timely extended surveillance. Short-term decisions and adoptions are likely for future campaigns, e. g., due to unexpected changes in the epidemic, demanding flexibility in the application management.

Pooling European all-cause mortality: methodology and findings for the seasons 2008/2009 to 2010/2011.

Several European countries have timely all-cause mortality monitoring. However, small changes in mortality may not give rise to signals at the national level. Pooling data across countries may overcome this, particularly if changes in mortality occur simultaneously. Additionally, pooling may increase the power of monitoring populations with small numbers of expected deaths, e.g. younger age groups or fertile women. Finally, pooled analyses may reveal patterns of diseases across Europe. We describe a pooled analysis of all-cause mortality across 16 European countries. Two approaches were explored. In the 'summarized' approach, data across countries were summarized and analysed as one overall country. In the 'stratified' approach, heterogeneities between countries were taken into account. Pooling using the 'stratified' approach was the most appropriate as it reflects variations in mortality. Excess mortality was observed in all winter seasons albeit slightly higher in 2008/09 than 2009/10 and 2010/11. In the 2008/09 season, excess mortality was mainly in elderly adults. In 2009/10, when pandemic influenza A(H1N1) dominated, excess mortality was mainly in children. The 2010/11 season reflected a similar pattern, although increased mortality in children came later. These patterns were less clear in analyses based on data from individual countries. We have demonstrated that with stratified pooling we can combine local mortality monitoring systems and enhance monitoring of mortality across Europe.

Excess mortality among the elderly in 12 European countries, February and March 2012.

In February and March 2012, excess deaths among the elderly have been observed in 12 European countries that carry out weekly monitoring of all-cause mortality. These preliminary data indicate that the impact of influenza in Europe differs from the recent pandemic and post-pandemic seasons. The current excess mortality among the elderly may be related to the return of influenza A(H3N2) virus, potentially with added effects of a cold snap.

Secondary transmissions during the outbreak of Shiga toxin-producing Escherichia coli O104 in Hesse, Germany, 2011.

During the recent outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 in Germany most cases notified in the State of Hesse (6 million inhabitants) were linked to satellite clusters or had travelled to the outbreak area in northern Germany. Intensified surveillance was introduced to rapidly identify cases not linked to known clusters or cases and thus to obtain timely information on possible further contaminated vehicles distributed in Hesse, as well to describe the risk of secondary transmission among known cases. As of 2 August 2011* [corrected], 56 cases of haemolytic uraemic syndrome (HUS) including two fatal cases, and 124 cases of STEC gastroenteritis meeting the national case definitions have been reported in Hesse. Among the 55 HUS and 81 STEC gastroenteritis cases thatmet the outbreak case definition, one HUS case and eight STEC gastroenteritis cases may have acquired their infection through secondary transmission. They include six possible transmissions within the family, two possible nosocomial and one possible laboratory transmission. Our results do not suggest an increased transmissibility of the outbreak strain compared to what is already known about E. coli O157 and other STEC serotypes.

[Timely registration of fatalities in the state of Hessen. Experiences during the influenza A/H1N1 pandemic]. / Zeitnahe Erfassung und Übermittlung von Todesfällen in Hessen. Eine erste Einschätzung zur Influenza-A/H1N1v-Pandemie.

Timely registration of fatalities is important for the assessment of course, extent, risk of age groups, and magnitude or severity of health threats. Nevertheless, timely data of casualties are not available on the state or national level. The current paper describes the implementation and structure of a surveillance system for the timely registration of casualties in the state of Hesse (Germany) and the experience obtained during the pandemic 2009/10. The delay of the case-based registration appears tolerable and after 2 weeks more than 80% of all deaths for a given week are registered. In 2008, the forwarding of the electronically registered data from the registry offices (95% of all cases) to the state statistical office (HSL) had been accelerated from a monthly to a weekly base. The HSL provides--on a weekly basis--this case-based data in accordance with data protection rules to the Hesse State Health Office (HLPUG, "Hessischer Landesprüfungs- und Untersuchungsamt im Gesundheitswesen"). During the pandemic, the data allowed assessment of the excess mortality with a delay of 2 weeks. No significant excess mortality was apparent; however, a slight increase was observed in the age groups 15-34, 35-49, and 50-59. Correlation of time with the severity of the A/H1N1v epidemic was not very strong. Hence, the data did not indicate an excess significantly exceeding the number of death cases registered with the mandatory reporting system of 21 cases for Hesse.

[The burden of acute gastrointestinal illness in Hesse--a telephone survey]. / Die Krankheitslast durch akute Gastroenteritiden in Hessen--ein Telefonsurvey.

INTRODUCTION: Mandatory notifications of laboratory diagnosed cases of acute gastroenteritis are essential for public health surveillance of food-borne diseases; however, reported cases represent a subset of infection in the community. We aimed to determine the magnitude and distribution of self-reported, acute gastrointestinal illness in Hesse, Germany, and to describe factors associated with seeking medical care. METHODS: We conducted a retrospective, cross-sectional telephone survey in 4 551 randomly selected households from September 2004 to August 2006. We used a standardised questionnaire to collect data on the interview partner and all children ≤ 15 years living in the household. The case definition was 3 or more loose stools or any vomiting in 24 h, during the 4 weeks preceding the interview, but excluding those with non-infectious causes. Frequency data were weighted to the Hessian population. RESULTS: Among the contacted households, 81% participated. 137 of the 2 100 children ≤ 15 years met the case definition, yielding an adjusted annual incidence rate of 0.86 (95% CI 0.72-1.03) episodes per person-year. 167 of the 4 551 study participants ≥ 16 years met the case definition, yielding an adjusted annual incidence rate of 0.46 (95% CI 0.37-0.51) episodes per person-year. This extrapolates to 807 000 (95% CI 672 000-962 000) cases of acute gastroenteritis in Hesse each year for children ≤ 15 years of age and 2 225 000 (95% CI 1 880 000-2 625 000) cases in individuals ≥ 16 years. On multivariate analysis, among individuals aged ≤ 15 years with an acute gastroenteritis, factors associated with seeking medical care included age, vomiting ≥ 3 times in 24 h, fever, and duration of illness. Among cases ≥ 16 years, duration of illness was associated with seeking medical care. Of those seeking medical care, 15% provided a stool sample. CONCLUSION: Acute gastrointestinal illness appears to pose a significant burden in the Hessian population. Cases of acute gastrointestinal illness ascertained through laboratory-based public health surveillance likely differ systematically from unreported cases. Further research into the pathogen-specific burden is needed to better target intervention strategies.

Urban-rural differences of age- and species-specific campylobacteriosis incidence, Hesse, Germany, July 2005 - June 2006.

Campylobacter infection is the most common cause of bacterial gastroenteritis worldwide. This study examines the association between campylobacteriosis incidence and degree of urbanicity in Hesse, Germany, by age and Campylobacter species. During a one-year period (July 2005­June 2006), Hessian local health authorities provided information on municipality of residence for 3,315 campylobacteriosis cases. We calculated age- and Campylobacter species-specific incidences for six levels of urbanicity, as defined by population density and accessibility of centres. For children under five years old, living in inner rural areas (incidence rate ratio (IRR): 2.9; 95% confidence interval (CI): 1.9 to 4.4) and for children aged 5­14 years living in inner rural (IRR: 2.1; 95% CI: 1.3 to 3.1) or intermediate areas (inner intermediate area IRR: 1.8; 95% CI: 1.2 to 2.7; outer intermediate area IRR: 2.1; 95% CI: 1.3 to 3.3) was associated with a statistically significantly higher campylobacteriosis risk (reference category: inner urban area). Calculations by Campylobacter species showed a higher risk of gastroenteritis due to C. coli for inhabitants (all ages) of non-urban areas. This study suggests that differences in risk factors by age, Campylobacter species and degree of urbanicity do exist. For children contact with animals or the environment may be responsible for a substantial proportion of sporadic Campylobacter infections.

Higher all-cause mortality in children during autumn 2009 compared with the three previous years: pooled results from eight European countries.

The paper describes weekly fluctuations of all-cause mortality observed in eight European countries during the period between week 27 and 51, 2009, in comparison with three previous years. Our preliminary data show that the mortality reported during the 2009 influenza pandemic did not reach levels normally seen during seasonal influenza epidemics. However, there was a cumulative excess mortality of 77 cases (1 per 100,000 population) in 5-14-year-olds, and possibly also among 0-4-year-olds.

Active immunisation during an outbreak of hepatitis A in a German day-care centre.

During an outbreak in a German day-care centre (DCC) caring for 100 children HAV vaccination was recommended for children, employees and household members of cases. A retrospective cohort study was done to evaluate vaccine uptake and identify possible risk factors for disease. Between 19 December 2004 and 30 January 2005 eight DCC children and seven household members fulfilled the case definition, i.e. had clinical hepatitis (14) or were diagnosed with asymptomatic HAV infection (1). Following the recommendation to vaccinate, given on 23 December 2004, 66.7% (46/69) of DCC children, 15.8% (29/184) of household members and 5/5 of employees were vaccinated, and three vaccinated children and two not vaccinated children fell ill. One of 11 children who received human normal immunoglobulin (HNIG) and four of 58 children who did not receive HNIG fell ill. In households in which the DCC child received HAV vaccine and/or HNIG, seven (5.6%) of 125 household members fulfilled the case definition. In households of non-immunised children none of the 59 household members fell ill. We conclude that, although most vaccinations were administered promptly, they may not have been timely enough to impact the course of the outbreak.

[Estimation of influenza vaccine effectiveness using routine surveillance data]. / Zur Schätzung der Schutzwirkung der Influenzaimpfung aus Surveillancedaten.

The continuous antigenic drift of influenza viruses requires annual adaptation of the vaccine. Protection depends largely on the match of the variants represented in the vaccine with the viruses actually known to be in circulation and may differ considerably from season to season. Therefore studies to assess the efficacy and effectiveness of the vaccine are conducted rather sporadically on an annual basis and it would be desirable to make use of routinely available data from surveillance programs. We compared two different approaches: (1) the "screening method" where cases are identified from laboratory data and controls are taken from data on vaccination rates and (2) a second method that uses the same cases, but controls were influenza-negative individuals with influenza-like illness (also identified from laboratory data). The sensitivity of the methods to confounders that were considered as relevant was tested with a simulation. Both methods were applied to the data of the German influenza surveillance data of the season 2004/2005. The estimated effectiveness over all age groups was rather low with both methods, but comparable with other estimations from the literature. We observed differences in certain age groups between the methods as well as large differences between particular age groups within one method. Possible explanations are random variations due to low numbers in age strata and other influences not yet considered. Therefore the estimations should be interpreted with care; however, relative comparisons among seasons may still be meaningful.

[Tasks, principles and methods of applied infectious disease epidemiology/field epidemiology]. / Aufgaben, Prinzipien und Methoden der angewandten/aufsuchenden Infektionsepidemiologie.

Applied infectious disease epidemiology/field epidemiology involves the application of epidemiologic methods to unexpected health problems when a rapid, on-site investigation is necessary for timely intervention. While field investigations of acute problems share the need of high methodological quality with prospectively planned studies, they may differ in several respects. In particular, because field investigations of ten start without a clear hypothesis, they may require the use of descriptive studies to generate a hypothesis before analytic studies are conducted. There also may be an immediate need to protect the population's health, pressure to intervene may conflict with the need to investigate and publicity may introduce bias. Outbreak investigations are paradigms of the use and methodology of applied infectious disease epidemiology/field epidemiology. The steps of an outbreak investigation include verification, confirming the diagnosis, developing a case definition and case finding, describing the data in terms of time, place and person, risk identification, formulating and testing of a hypothesis, planning for further studies, establishing control measures and communicating the findings.

[Calculation of the incidence of primary care visits due to acute respiratory infections]. / Zur Schätzung der Konsultationsinzidenz akuter respiratorischer Erkrankungen aus Praxisdaten.

Data collected by the German influenza sentinel of the Working Group on Influenza (AGI) do not allow calculation of the incidence of primary care visits due to acute respiratory infections (ARI). Because patients do not have to register with a particular general practitioner, the population covered by primary care physicians is unknown. Until now the incidence of primary care visits due to ARI is estimated indirectly by extrapolating the sentinel sample of physicians to the total number of primary care physicians caring for the total population. However, distortions of the estimated incidence occur in weeks with public holidays (particularly around Christmas and New Year) and when many physicians close their practice simultaneously because of vacation. We have attempted to quantify the shortage of medical services and established thresholds to correct for situations where service by medical providers is extraordinarily reduced. The suggested method avoids distortions to a large extent and makes interpretation of data during those critical periods possible. A second subject of the paper is the validation of the estimated ARI incidence in primary care practices by comparing the data to other sources such as sick leave statistics of health insurance as well as ICD-based data from a primary care network. We found that the estimated ARI incidence in primary care practices was in line with data from other sources and appears plausible.

Are influenza surveillance data useful for mapping presentations?

Geographical information system (GIS) based on mappings of influenza data are rare (http://www.b3e.jussieu.fr.80/sentiweb/fr) and influenza data are commonly aggregated for rather large areas (http://www.eiss.org, http://oms2b3e.jussieu.fr/FluNet). The most limiting factors for the use of morbidity-data from practices in GIS-based mappings are differences which are not related to morbidity. These differences may be due to consultation behaviour, interpretation of the case definition, age distribution of patients and other reasons. In order to reduce the impact of these non-morbidity related differences on the interpretation, the data of many practices are usually pooled and consequently rather large areas are presented. Extracting and harmonising the signals for increased morbidity from practices is a presupposition for mapping with a sufficient geographical resolution. The possibility to harmonise by reducing those confounding differences on a practice level is investigated. Different harmonisation methods were applied to data from Germany where acute respiratory infections (ARI) per consultations are registered and from The Netherlands were influenza like illnesses (ILI) per population are registered. The harmonisation of the indices between countries was achieved by scaling them in relation to the level of the index representative for the peak activity during a usual influenza epidemic. The Kriging method is applied as a means of spatial prediction for the influenza data. The preliminary results are discussed with respect to resulting mappings.

Influenza-associated excess mortality from monthly total mortality data for Germany from 1947 to 2000.

OBJECTIVES: Death attributable to influenza is noted under various causes in the mortality statistics. Therefore, excess of total mortality is frequently used for the estimation of the entire impact of influenza on mortality. Various models for the estimation of the expected mortality are in use but are rather complex which hampers their routine use. A simple and hence transparent model was developed and applied to the total mortality in Germany from 1947 to 2000. METHODS: The method is based on the pattern of the distribution of the mortality over the months. Additional trends over the time could be included with simple factors. In this manner the model was applicable over the total observation period. RESULTS: The fit for the months where influenza was not epidemic was good and comparable to other models (R2 = 0.91). The estimated excess mortality is plausible and congruent with estimates based on other models. CONCLUSION: This method is applicable to long time series of any duration and obvious trends could be considered by simple factors in a readily identifiable and plausible way. Possible reductions in precision due to the consideration of a given monthly distribution pattern of the annual mortality seem tolerable with respect to the goodness of fit of the model. The estimation includes the pandemics of 1957/58 and 1968 to 1970.

Heterogeneous case definitions used for the surveillance of influenza in Europe.

We reviewed the case definitions used by 21 influenza sentinel-based surveillance networks in Western Europe. Two clinical syndromes were used with a wide range of case definitions that nevertheless shared common criteria. Although there is currently no international consensus, efforts are being undertaken to standardise influenza case definitions in Europe.

Harmonisation of national influenza surveillance morbidity data from EISS: a simple index.

The European Influenza Surveillance Scheme is a collaboration with 18 member countries (2001/02) which monitors the activity and impact of influenza by collecting morbidity and virological data in primary care facilities throughout the winter season each year. Despite being in principle similar in the surveillance concept, the indicators used and observations made are very different. Different healthcare systems and organisational needs (eg a certificate of illness for the employer) influence the consultation behaviour. Furthermore, and partly as a result of differences in the healthcare systems, the definitions used for the numerator and denominator when calculating morbidity rates are different. Thus comparative interpretation of participating countries' morbidity data is extremely difficult. Reporting 'harmonisation' by using equivalent numerators and denominators is one option but is difficult to achieve in the short term. Moreover, several additional issues would need to be considered, for example, the need for continuity of surveillance and whether such steps would indeed result in direct comparability etc. A simple index was tested, through which the impact of influenza morbidity in any one year is compared with what is considered a 'usual' epidemic in that country. The index in principle describes numerically the extent to which the influenza-attributable excess morbidity in the current epidemic in each country is within, exceeds, or is less than a range typical for an influenza epidemic. In this pilot study, the usefulness of such an index is explored with the example of eight countries for the seasons 1999/2000 and 2000/01. A fine tuning of the methods has not yet been performed.

Some aspects regarding the interpretation of influenza surveillance data.

For influenza monitoring, the use of laboratory data usually in combination with morbidity data from primary care facilities is common. The estimated excess morbidity, or resulting rates and consultation incidences are the basic parameter for the estimation of influenza activity in conjunction with antigen assays of influenza in a selected sub-sample of the recorded patients. The interpretation of such data is complicated by several selection processes, confounding influences and bias. The case definition (CD) given for the selection of cases is important for the sensitivity and specificity of the registrations. For the clinical morbidity data, the lower specificity found when more general (acute respiratory tract infections) criteria are used seems to be compensated by a higher statistical sensitivity due to the larger number of cases. The relative stability of the background morbidity against the expected values is critical for the interpretation. The sub-sample of patients tested by antigen assays is usually small due to cost constraints. Testing all patients with the defined symptoms in a sub-sample of practices is rarely possible because of the workload in the GPs offices during an influenza epidemic but does allow the number of positives to be used as an indicator. Usually, a sub-sample of GPs is asked to test a limited number of patients suffering with the symptoms given as selection criteria. In this case, the rate of positives is the better indicator for the influenza activity. However, the low number of tests particularly when flu is circulating at a low level limits the statistical sensitivity of this parameter. The specificity of the criteria given for the selection of patients being swabbed and the sensitivity of the test largely determine the function between the rate of positives and the influenza activity. The virological results are mostly interpreted in a more qualitative way, to see if influenza is circulating significantly. For this interpretation, more specific selection criteria (CD) seem useful and a high sensitivity for an increasing circulation can be expected.