Novel Methods in the Surveillance of Influenza-Like Illness in Germany Using Data From a Symptom Assessment App (Ada): Observational Case Study.

BACKGROUND: Participatory epidemiology is an emerging field harnessing consumer data entries of symptoms. The free app Ada allows users to enter the symptoms they are experiencing and applies a probabilistic reasoning model to provide a list of possible causes for these symptoms. OBJECTIVE: The objective of our study is to explore the potential contribution of Ada data to syndromic surveillance by comparing symptoms of influenza-like illness (ILI) entered by Ada users in Germany with data from a national population-based reporting system called GrippeWeb. METHODS: We extracted data for all assessments performed by Ada users in Germany over 3 seasons (2017/18, 2018/19, and 2019/20) and identified those with ILI (report of fever with cough or sore throat). The weekly proportion of assessments in which ILI was reported was calculated (overall and stratified by age group), standardized for the German population, and compared with trends in ILI rates reported by GrippeWeb using time series graphs, scatterplots, and Pearson correlation coefficient. RESULTS: In total, 2.1 million Ada assessments (for any symptoms) were included. Within seasons and across age groups, the Ada data broadly replicated trends in estimated weekly ILI rates when compared with GrippeWeb data (Pearson correlation-2017-18: r=0.86, 95% CI 0.76-0.92; P<.001; 2018-19: r=0.90, 95% CI 0.84-0.94; P<.001; 2019-20: r=0.64, 95% CI 0.44-0.78; P<.001). However, there were differences in the exact timing and nature of the epidemic curves between years. CONCLUSIONS: With careful interpretation, Ada data could contribute to identifying broad ILI trends in countries without existing population-based monitoring systems or to the syndromic surveillance of symptoms not covered by existing systems.

Ten years of weekly epidemiological teleconference (EpiLag) - an effective and time-efficient tool for infectious disease event information, Germany, 2009-2018.

In 2009, the Robert Koch Institute (RKI) and the 16 German federal state public health authorities (PHAs) established a weekly epidemiological teleconference (EpiLag) to discuss infectious disease (ID) events and foster horizontal and vertical information exchange. We present the procedure, discussed ID topics and evaluation results of EpiLag after 10 years. We analysed attendance, duration of EpiLag and the frequency of reported events. Participants (RKI and state PHA) were surveyed regarding their satisfaction with logistics, contents and usefulness of EpiLag (Likert scales). Between 2009 and 2018, RKI hosted 484 EpiLag conferences with a mean duration of 25 min (range: 4-60) and high participation (range: 9-16; mean: 15 PHAs). Overall, 2975 ID events (39% international, 9% national and 52% subnational) were presented (mean: 6.1 per EpiLag), most frequently on measles (18%), salmonellosis (8%) and influenza (5%). All responding participants (14/16 PHAs and 9/9 at RKI) were satisfied with the EpiLag's organization and minutes and deemed EpiLag useful for an overview and information distribution on ID events relevant to Germany. EpiLag is time efficient, easily applicable and useful for a low-threshold event communication. It supports PHAs in crises and strengthens the network of surveillance stakeholders. We recommend its implementation to other countries or sectors.

Syndromic Surveillance Insights from a Symptom Assessment App Before and During COVID-19 Measures in Germany and the United Kingdom: Results From Repeated Cross-Sectional Analyses.

BACKGROUND: Unprecedented lockdown measures have been introduced in countries worldwide to mitigate the spread and consequences of COVID-19. Although attention has been focused on the effects of these measures on epidemiological indicators relating directly to the infection, there is increased recognition of their broader health implications. However, assessing these implications in real time is a challenge, due to the limitations of existing syndromic surveillance data and tools. OBJECTIVE: The aim of this study is to explore the added value of mobile phone app-based symptom assessment tools as real-time health insight providers to inform public health policy makers. METHODS: A comparative and descriptive analysis of the proportion of all self-reported symptoms entered by users during an assessment within the Ada app in Germany and the United Kingdom was conducted between two periods, namely before and after the implementation of "Phase One" COVID-19 measures. Additional analyses were performed to explore the association between symptom trends and seasonality, and symptom trends and weather. Differences in the proportion of unique symptoms between the periods were analyzed using a Pearson chi-square test and reported as log2 fold changes. RESULTS: Overall, 48,300-54,900 symptomatic users reported 140,500-170,400 symptoms during the Baseline and Measures periods in Germany. Overall, 34,200-37,400 symptomatic users in the United Kingdom reported 112,100-131,900 symptoms during the Baseline and Measures periods. The majority of symptomatic users were female (Germany: 68,600/103,200, 66.52%; United Kingdom: 51,200/71,600, 72.74%). The majority were aged 10-29 years (Germany: 68,500/100,000, 68.45%; United Kingdom: 50,900/68,800, 73.91%), and about one-quarter were aged 30-59 years (Germany: 26,200/100,000, 26.15%; United Kingdom: 14,900/68,800, 21.65%). Overall, 103 symptoms were reported either more or less frequently (with statistically significant differences) during the Measures period as compared to the Baseline period, and 34 of these were reported in both countries. The following mental health symptoms (log2 fold change, P value) were reported less often during the Measures period: inability to manage constant stress and demands at work (-1.07, P<.001), memory difficulty (-0.56, P<.001), depressed mood (-0.42, P<.001), and impaired concentration (-0.46, P<.001). Diminished sense of taste (2.26, P<.001) and hyposmia (2.20, P<.001) were reported more frequently during the Measures period. None of the 34 symptoms were found to be different between the same dates in 2019. In total, 14 of the 34 symptoms had statistically significant associations with weather variables. CONCLUSIONS: Symptom assessment apps have an important role to play in facilitating improved understanding of the implications of public health policies such as COVID-19 lockdown measures. Not only do they provide the means to complement and cross-validate hypotheses based on data collected through more traditional channels, they can also generate novel insights through a real-time syndromic surveillance system.

Positive predictive value of the German notification system for infectious diseases: Surveillance data from eight local health departments, Berlin, 2012.

The German Infection Protection Act requires notifying certain cases of infectious diseases to local health departments (LHD) in Germany. LHDs transmit notifications meeting case definitions to the national health authority, where the proportion of discarded notifications is not known. The proportion of discarded cases at the level of LHDs can be expressed as the positive predictive value (PPV) of the notification system. The PPV can be used to assess the efficiency of the system. We quantified the proportion of discarded notifications to calculate the PPV of the German notification system at the level of LHDs using electronic notification data from Berlin LHDs from 2012. We also analysed reasons for discarding notifications by reviewing notification forms. Data was available from eight LHDs (67%) receiving 10,113 notifications in 2012. Overall PPV was 89% (minimum-maximum = 77-97% across LHDs) and ranging from 30% (Hepatitis B) to 99% (Rotavirus). Of 166 individual investigation forms 84% were on hepatitis B or C cases, most of them discarded because of previously diagnosed chronic disease. LHDs investigate many notifications that do not lead to public health action and useful surveillance data leading to inefficient use of resources. Adaptation of case definitions or the legal framework concerning notifications may increase the efficiency of the notification system and lead to better use of data from notified cases.

Timeliness in the German surveillance system for infectious diseases: Amendment of the infection protection act in 2013 decreased local reporting time to 1 day.

Time needed to report surveillance data within the public health service delays public health actions. The amendment to the infection protection act (IfSG) from 29 March 2013 requires local and state public health agencies to report surveillance data within one working day instead of one week. We analysed factors associated with reporting time and evaluated the IfSG amendment. Local reporting time is the time between date of notification and date of export to the state public health agency and state reporting time is time between date of arrival at the state public health agency and the date of export. We selected cases reported between 28 March 2012 and 28 March 2014. We calculated the median local and state reporting time, stratified by potentially influential factors, computed a negative binominal regression model and assessed quality and workload parameters. Before the IfSG amendment the median local reporting time was 4 days and 1 day afterwards. The state reporting time was 0 days before and after. Influential factors are the individual local public health agency, the notified disease, the notification software and the day of the week. Data quality and workload parameters did not change. The IfSG amendment has decreased local reporting time, no relevant loss of data quality or identifiable workload-increase could be detected. State reporting time is negligible. We recommend efforts to harmonise practices of local public health agencies including the exclusive use of software with fully compatible interfaces.

Two consecutive large outbreaks of Salmonella Muenchen linked to pig farming in Germany, 2013 to 2014: Is something missing in our regulatory framework?

In 2013, raw pork was the suspected vehicle of a large outbreak (n = 203 cases) of Salmonella Muenchen in the German federal state of Saxony. In 2014, we investigated an outbreak (n = 247 cases) caused by the same serovar affecting Saxony and three further federal states in the eastern part of Germany. Evidence from epidemiological, microbiological and trace-back investigations strongly implicated different raw pork products as outbreak vehicles. Trace-back analysis of S. Muenchen-contaminated raw pork sausages narrowed the possible source down to 54 pig farms, and S. Muenchen was detected in three of them, which traded animals with each other. One of these farms had already been the suspected source of the 2013 outbreak. S. Muenchen isolates from stool of patients in 2013 and 2014 as well as from food and environmental surface swabs of the three pig farms shared indistinguishable pulsed-field gel electrophoresis patterns. Our results indicate a common source of both outbreaks in the primary production of pigs. Current European regulations do not make provisions for Salmonella control measures on pig farms that have been involved in human disease outbreaks. In order to prevent future outbreaks, legislators should consider tightening regulations for Salmonella control in causative primary production settings.

Contact investigation after a fatal case of extensively drug-resistant tuberculosis (XDR-TB) in an aircraft, Germany, July 2013.

In July 2013, a passenger died of infectious extensively drug-resistant tuberculosis (XDR-TB) on board of an aircraft after a 3-hour flight from Turkey to Germany. Initial information indicated the patient had moved about the aircraft coughing blood. We thus aimed to contact and inform all persons exposed within the aircraft and to test them for newly acquired TB infection. Two-stage testing within 8 weeks from exposure and at least 8 weeks after exposure was suggested, using either interferon gamma release assays (IGRAs) or tuberculin skin test (TST). The TST cut-off was defined at a diameter > 10 mm; for differentiation between conversion and boosting, conversion was defined as increase of skin induration > 5 mm. Overall, 155 passengers and seven crew members were included in the investigation: the questionnaire response rate was 83%; 112 (69%) persons were tested at least once for TB infection. In one passenger, who sat next to the area where the patient died, a test conversion was registered. As of March 2017, no secondary active TB cases have been reported. We describe an unusual situation in which we applied contact tracing beyond existing European guidelines; we found one latent tuberculosis infection in a passenger, which we consider probably newly acquired.

Health and healthcare provision to asylum seekers and refugees in Germany.

The wars and devastation of recent years have driven many people to flee their homes. Great numbers of asylum seekers and refugees have sought protection in Europe. In 2015 and 2016 alone, over one million people applied for asylum in Germany. This has posed a great challenge for Germany's healthcare provision facilities. The health of asylum seekers and refugees and the provision of their healthcare is therefore an important issue in terms of public health. The first part of this article describes the extent and legal framework of immigration to Germany during the past two years. The second part then discusses the issue of health and medical care for asylum seekers and refugees. Until now, no representative data on the health of this population exists. Studies so far have all relied on a small number of cases and been limited to particular regions and are therefore hard to compare. Moreover, there are no sufficiently standardised medical examinations during initial reception across all German federal states. Relevant findings suggest an urgent need to take action in the fields of mental health, chronic diseases and the provision of care to children of asylum seekers. A review of the data available proves the need for a national and systematic collection of valid data as a basis for adequate preventive and medical care. Different initiatives currently aim to improve the data collection basis in Germany. Over time, these new initiatives will significantly improve the data available on the health situation of asylum seekers and refugees in Germany. Once politics and broader society take these findings into account, this should contribute to an objective debate and evidence-based decisions.

[Infectious disease outbreaks in centralized homes for asylum seekers in Germany from 2004-2014]. / Ausbrüche von Infektionskrankheiten in Gemeinschaftsunterkünften für Asylsuchende 2004-2014 in Deutschland.

BACKGROUND: Migration and imported infections are changing the distribution of infectious diseases in Europe. However little is known about the extent of transmission of imported diseases within Europe. Asylum seekers are of increasing importance for infectious disease epidemiology and can be particularly vulnerable for infections and disease progression due to stressful conditions of migration and incomplete vaccination status. OBJECTIVES: The aim is to analyse transmission of infectious diseases in centralized homes for asylum seekers in national infectious disease surveillance data to identify relevant infectious diseases and possible public health measures to reduce transmission. METHODS: German national notification data was systematically analysed from 2004 to 2014 for outbreaks reported to have occurred within centralized homes for asylum seekers followed by descriptive analysis of outbreak- and case-characteristics. RESULTS: From 2004 to 2014 the number of outbreaks in centralized homes for asylum seekers per year increased, a total of 119 outbreaks with 615 cases were reported. Cases in these outbreaks were caused by chicken pox (30 %), measles (20 %), scabies (19 %), rota-virus-gastroenteritis (8 %) and others (each <5 %). Of 119 outbreaks, two outbreaks of measles in centralized homes were connected to outbreaks outside the centralized homes. For 210 of 311 cases in 2014 the place of infection was reported, 87 % of those with known place of infection were infected in Germany. CONCLUSIONS: Infectious disease outbreaks in centralized homes for asylum seekers are reported increasingly often in Germany. Chicken pox, measles and scabies were the most frequent outbreak causing diseases. Spread of such outbreaks outside centralized homes for asylum seekers was rare and infectious diseases are mainly acquired in Germany. The majority of outbreaks in centralized homes for asylum seekers would be preventable with vaccinations at arrival and appropriate hygiene measures.

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.

Serological evidence of asymptomatic infections during Escherichia coli O104:H4 outbreak in Germany in 2011.

INTRODUCTION: The largest known outbreak caused by a rare hybrid strain of Shiga toxin-producing E.coli (STEC) and enteroaggregative E. coli (EAEC) (E.coli O104:H4) of serotype O104:H4 occurred in Germany in 2011. Fenugreek sprouts acted as a transmission vehicle and were widely consumed in the outbreak area at the time of the epidemic. In total 3,842 people developed a clinical illness caused by this strain; however the rates of asymptomatic infections remain unclear. We aimed to develop a serological assay for detection of E.coli O104 LPS specific antibodies and to establish the post-outbreak levels of seropositivity among people with documented exposure to contaminated sprouts. RESULTS AND DISCUSSION: Developed serological assays (ELISA with 84% sensitivity, 63% specificity and Western Blot with 100% sensitivity, 82.5% specificity) identified 33% (16/49) level of asymptomatic infection. Relatively small sample size and a significant time- lapse between the onset of symptoms and serum samples collection (appr. 8 weeks) might explain the assay variability. No association was found between clinical or demographic characteristics and assay positivity. Larger studies are needed to understand the complexity of human immune response and factors influencing development of clinical symptoms. Development of intra-outbreak research plans will substantially aid the conduct of more thorough scientific investigation during an outbreak period.

Guidance for contact tracing of cases of Lassa fever, Ebola or Marburg haemorrhagic fever on an airplane: results of a European expert consultation.

BACKGROUND: Travel from countries where viral haemorrhagic fevers (VHF) are endemic has increased significantly over the past decades. In several reported VHF events on airplanes, passenger trace back was initiated but the scale of the trace back differed considerably. The absence of guidance documents to help the decision on necessity and scale of the trace back contributed to this variation.This article outlines the recommendations of an expert panel on Lassa fever, Ebola and Marburg haemorrhagic fever to the wider scientific community in order to advise the relevant stakeholders in the decision and scale of a possible passenger trace back. METHOD: The evidence was collected through review of published literature and through the views of an expert panel. The guidance was agreed by consensus. RESULTS: Only a few events of VHF cases during air travel are reported in literature, with no documented infection in followed up contacts, so that no evidence of transmission of VHF during air travel exists to date. Based on this and the expert opinion, it was recommended that passenger trace back was undertaken only if: the index case had symptoms during the flight; the flight was within 21 days after detection of the event; and for Lassa fever if exposure of body fluid has been reported. The trace back should only be done after confirmation of the index case. Passengers and crew with direct contact, seat neighbours (+/- 1 seat), crew and cleaning personal of the section of the index case should be included in the trace back. CONCLUSION: No evidence has been found for the transmission of VHF in airplanes. This information should be taken into account, when a trace back decision has to be taken, because such a measure produces an enormous work load. The procedure suggested by the expert group can guide decisions made in future events, where a patient with suspected VHF infection travelled on a plane. However, the actual decision on start and scale of a trace back always lies in the hands of the responsible people taking all relevant information into account.

Communicable diseases prioritized for surveillance and epidemiological research: results of a standardized prioritization procedure in Germany, 2011.

INTRODUCTION: To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research. METHODS: We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups. RESULTS: 127 pathogens were scored. Eighty-six experts participated in the weighting; "Case fatality rate" was rated as the most important criterion. Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.), and nosocomial pathogens associated with antimicrobial resistance. Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus. DISCUSSION: While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings.

The first wave of pandemic influenza (H1N1) 2009 in Germany: from initiation to acceleration.

BACKGROUND: The first imported case of pandemic influenza (H1N1) 2009 in Germany was confirmed in April 2009. However, the first wave with measurable burden of disease started only in October 2009. The basic epidemiological and clinical characteristics of the pandemic were analysed in order to understand the course of the pandemic in Germany. METHODS: The analysis was based on data from the case-based, mandatory German surveillance system for infectious diseases. Cases notified between 27 April and 11 November 2009 and fulfilling the case definition were included in the study. RESULTS: Two time periods with distinct epidemiologic characteristics could be determined: 23,789 cases (44.1%) occurred during the initiation period (IP, week 18 to 41), and 30,179 (55.9%) during the acceleration period (AP, week 42 to 45). During IP, coinciding with school summer holidays, 61.1% of cases were travel-related and one death occurred. Strict containment efforts were performed until week 32. During AP the majority of cases (94.3%) was autochthonous, 12 deaths were reported. The main affected age group shifted from 15 to 19 years in IP to 10 to 14 years in AP (median age 19 versus 15 years; p < 0.001). The proportion of cases with underlying medical conditions increased from 4.7% to 6.9% (p < 0.001). Irrespective of the period, these cases were more likely to be hospitalised (OR = 3.6 [95% CI: 3.1; 4.3]) and to develop pneumonia (OR = 8.1 [95% CI: 6.1; 10.7]). Furthermore, young children (0 to 2 years) (OR = 2.8 [95% CI: 1.5; 5.2]) and persons with influenza-like illness (ILI, OR = 1.4 [95% CI: 1.0; 2.1]) had a higher risk to develop pneumonia compared to other age groups and individuals without ILI. CONCLUSION: The epidemiological differences we could show between summer and autumn 2009 might have been influenced by the school summer holidays and containment efforts. The spread of disease did not result in change of risk groups or severity. Our results show that analyses of case-based information can advise future public health measures.

Highly variable use of diagnostic methods for sexually transmitted infections-results of a nationwide survey, Germany 2005.

BACKGROUND: Sexual transmitted infections (STIs) have increased in Germany and other countries in Europe since the mid-nineties. To obtain a better picture of diagnostic methods used in STI testing institutions in Germany, we performed a nationwide survey amongst STI specialists in order to evaluate the quality of STI reports and provide recommendations to harmonize and possibly improve STI diagnostics in Germany. METHODS: We asked sentinel physicians and randomly chosen gynaecologists, urologists and dermato-venerologists, about the diagnostic methods used in 2005 to diagnose HIV, chlamydia (CT), gonorrhoea (GO) and syphilis (SY) in a national cross-sectional survey in order to recognize potential problems and provide recommendations. RESULTS: A total of 739/2287 (32%) physicians participated. Of all participants, 80% offered tests for HIV, 84% for CT, 83% for GO and 83% for SY. Of all participants who performed HIV testing, 90% requested an antibody test, 3% a rapid test and 1% a nucleic acid amplification test (NAAT). For CT testing, NAAT was used in 33% and rapid tests in 34% of participants. GO resistance testing was performed by 31% of the participants. SY testing was performed in 98% by serology. CONCLUSIONS: Diagnostic methods for STI vary highly among the participants. Diagnostic guidelines should be reviewed and harmonised to ensure consistent use of the optimal STI diagnostic methods.

Influenza A(H1N1)v in Germany: the first 10,000 cases.

The analysis of the first 10,000 cases of influenza A(H1N1)v in Germany confirms findings from other sources that the virus is currently mainly causing mild diseases, affecting mostly adolescents and young adults. Overall hospitalisation rate for influenza A(H1N1)v was low (7%). Only 3% of the cases had underlying conditions and pneumonia was rare (0.4%). Both reporting and testing requirements have been adapted recently, taking into consideration the additional information available on influenza A(H1N1)v infections.