Geographical differences of carbapenem non-susceptible Enterobacterales and Acinetobacter spp. in Germany from 2017 to 2019.

BACKGROUND: Since May 2016, infection and colonisation with carbapenem non-susceptible Acinetobacter spp. (CRA) and Enterobacterales (CRE) have to be notified to health authorities in Germany. The aim of our study was to assess the epidemiology of CRA and CRE from 2017 to 2019 in Germany, to identify risk groups and to determine geographical differences of CRA and CRE notifications. METHODS: Cases were notified from laboratories to local public health authorities and forwarded to state and national level. Non-susceptibility was defined as intermediate or resistant to ertapenem, imipenem, or meropenem excluding intrinsic bacterial resistance or the detection of a carbapenemase gene. We analysed CRA and CRE notifications from 2017, 2018 and 2019 per 100,000 inhabitants (notification incidence), regarding their demographic, clinical and laboratory information. The effect of regional hospital-density on CRA and CRE notification incidence was estimated using negative binomial regression. RESULTS: From 2017 to 2019, 2278 CRA and 12,282 CRE cases were notified in Germany. CRA and CRE cases did not differ regarding demographic and clinical information, e.g. proportion infected. The notification incidence of CRA declined slightly from 0.95 in 2017 to 0.86 in 2019, whereas CRE increased from 4.23 in 2017 to 5.72 in 2019. The highest CRA and CRE notification incidences were found in the age groups above 70 years. Infants below 1 year showed a high CRE notification incidence, too. Notification incidences varied between 0.10 and 2.86 for CRA and between 1.49 and 9.99 for CRE by federal state. The notification incidence of CRA and CRE cases increased with each additional hospital per district. CONCLUSION: The notification incidence of CRA and CRE varied geographically and was correlated with the number of hospitals.The results support the assumption that hospitals are the main driver for higher CRE and CRA incidence. Preventive strategies and early control measures should target older age groups and newborns and areas with a high incidence.

[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.

Completeness of tuberculosis case notifications in Germany in 2013-2017: first results of an inventory study.

BACKGROUND: Evaluating the completeness of tuberculosis (TB) notification data is important for monitoring of TB surveillance systems. We conducted an inventory study to calculate TB underreporting in Germany in 2013-2017. METHODS: Acquisition of two pseudonymized case-based data sources (national TB notification data and antibiotic resistance surveillance data) was followed by two-source Capture-recapture (CRC) analysis, as case-based data from a third source was unavailable. Aggregated data on consumption of a key anti-TB drug (pyrazinamide [PZA]) was compared to an estimated need for PZA based on TB notification data to obtain an independent underreporting estimation. Additionally, notified TB incidence was compared to TB rate in an aggregated health insurance fund dataset. RESULTS: CRC and PZA-based approaches indicated that between 93 and 97% (CRC) and between 91 and 95% (PZA) of estimated cases were captured in the national TB notification data in the years 2013-2017. Insurance fund dataset did not indicate TB underreporting on the national level in 2017. CONCLUSIONS: Our results suggest that more than 90% of estimated TB cases are captured within the German TB surveillance system, and accordingly the TB notification rate is likely a good proxy of the diagnosed TB incidence rate. An increase in underreporting and discrepancies however should be further investigated.

Differential Seasonality of Legionnaires' Disease by Exposure Category.

Legionnaires' disease (LD) shows a seasonal pattern with most cases occurring in summer. We investigate if seasonality can be observed for all three exposure categories (community-acquired (CALD), travel-associated (TALD) and healthcare-associated (HCA)). METHODS: LD cases (2005-2015) were classified by exposure categories and we calculated the relative case ratio for each month from February to December using January as reference. The TALD relative case ratio was compared with flight frequencies. RESULTS: Overall case numbers in Germany (N = 7351) peaked in August. CALD had a curve similar to all cases. TALD displayed a bimodal curve with peaks in June/July and October. The latter was attributable to LD cases aged 60+. The relative case ratio of TALD surpassed clearly that of CALD. The curve was similar to that of the relative flight frequencies, but was shifted by about one month. HCA showed no apparent seasonality. CONCLUSIONS: Although the overall seasonality in LD is heavily influenced by CALD, seasonal differences are more pronounced for TALD which may reflect travel behavior. The bimodal pattern of TALD is attributable to the curve among those aged 60+ and may reflect their preference to travel outside school holiday periods. Heightened vigilance for HCA cases is necessary throughout the entire year.

First-line tuberculosis drug resistance patterns and associated risk factors in Germany, 2008-2017.

BACKGROUND: Drug-resistant tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), poses a threat to public health. While standard surveillance focuses on Rifampicin and/or Isoniazid resistance, little is known about other resistance patterns. This study aims to identify predominant drug resistance (DR) patterns in Germany and risk factors associated with them in order to inform diagnostic and treatment strategies. METHODS: Case-based TB surveillance data notified in Germany from 2008-2017 were utilized to investigate DR and MDR-TB patterns for Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E), and Streptomycin (S). Predominant patterns were further analyzed stratified by sex, age, country of birth, prior TB, and disease site. Multivariable logistic regression was conducted to determine risk factors associated with any resistance, MDR-TB, and complete HRZES resistance. RESULTS: 26,228 cases with complete DST results were included in the study, among which 3,324 cases had any DR (12.7%). Four patterns were predominant, representing about ¾ of all cases with any resistance (S: 814 [3.1%]; H: 768 [2.9%]; HS: 552 [2.1%]; Z: 412 [1.6%]). High proportions of S and H resistances were found among both German and foreign-born populations, especially those born in Eastern Europe, and were unexpectedly high among children (H: 4.3%; S: 4.6%). Foreign-born cases had significantly higher proportion of any resistance (16.0%) and MDR-TB (3.3%) compared to German-born cases (8.3% and 0.6%). Of 556 MDR-TB cases, 39.2% showed complete HRZES resistance. Logistic regression revealed having prior TB and being foreign-born as consistently strong risk factors for any DR, MDR-TB, and complete HRZES resistance. CONCLUSIONS: DR patterns observed in Germany, particularly for MDR-TB were more complex than expected, highlighting the fact that detailed drug-testing results are crucial before incorporating HRZES drugs in MDR-TB treatment. Furthermore, the relatively high rate of H-resistance in Germany provides strong rationale against the use of only H-based preventive therapy for LTBI.

Epidemiology of Tick-Borne Encephalitis (TBE) in Germany, 2001⁻2018.

We reviewed tick-borne encephalitis (TBE) surveillance and epidemiology in Germany, as these underlie public health recommendations, foremost vaccination. We performed descriptive analyses of notification data (2001⁻2018, n = 6063) according to region, demographics and clinical manifestations and calculated incidence trends using negative binomial regression. Risk areas were defined based on incidence in administrative districts. Most cases (89%) occurred in the federal states of Baden-Wurttemberg and Bavaria, where annual TBE incidence fluctuated markedly between 0.7⁻2.0 cases/100,000 inhabitants. A slight but significantly increasing temporal trend was observed from 2001⁻2018 (age-adjusted incidence rate ratio (IRR) 1.02 (95% confidence interval (CI): 1.01⁻1.04)), primarily driven by high case numbers in 2017⁻2018. Mean incidence was highest in 40⁻69-year-olds and in males. More males (23.7%) than females (18.0%, p = 0.02) had severe disease (encephalitis or myelitis), which increased with age, as did case-fatality (0.4% overall; 2.1% among ≥70-year-olds). Risk areas increased from 129 districts in 2007 to 161 in 2019. Expansion occurred mainly within existent southern endemic areas, with slower contiguous north-eastern and patchy north-western spread. Median vaccination coverage at school entry in risk areas in 2016⁻2017 ranged from 20%⁻41% in 4 states. Increasing TBE vaccine uptake is an urgent priority, particularly in high-incidence risk areas.

Timeliness of surveillance during outbreak of Shiga Toxin-producing Escherichia coli infection, Germany, 2011.

In the context of a large outbreak of Shiga toxin-producing Escherichia coli O104:H4 in Germany, we quantified the timeliness of the German surveillance system for hemolytic uremic syndrome and Shiga toxin-producing E. coli notifiable diseases during 2003-2011. Although reporting occurred faster than required by law, potential for improvement exists at all levels of the information chain.

Effectiveness of the AS03-adjuvanted vaccine against pandemic influenza virus A/(H1N1) 2009--a comparison of two methods; Germany, 2009/10.

During the autumn wave of the pandemic influenza virus A/(H1N1) 2009 (pIV) the German population was offered an AS03-adjuvanted vaccine. The authors compared results of two methods calculating the effectiveness of the vaccine (VE). The test-negative case-control method used data from virologic surveillance including influenza-positive and negative patients. An innovative case-series methodology explored data from all nationally reported laboratory-confirmed influenza cases. The proportion of reported cases occurring in vaccinees during an assumed unprotected phase after vaccination was compared with that occurring in vaccinees during their assumed protected phase. The test-negative case-control method included 1,749 pIV cases and 2,087 influenza test-negative individuals of whom 6 (0.3%) and 36 (1.7%), respectively, were vaccinated. The case series method included data from 73,280 cases. VE in the two methods was 79% (95% confidence interval (CI) = 35-93%; P = 0.007) and 87% (95% CI = 78-92%; P<0.001) for individuals less than 14 years of age and 70% (95% CI = -45%-94%, P = 0.13) and 74% (95% CI = 64-82%; P<0.001) for individuals above the age of 14. Both methods yielded similar VE in both age groups; and VE for the younger age group seemed to be higher.

High level of gastrointestinal nosocomial infections in the german surveillance system, 2002-2008.

OBJECTIVE: Surveillance of nosocomial infections (NIs) is well established in many countries but often does not include gastrointestinal infections. We sought to determine the proportion of NIs among all hospitalized cases for the 4 most prevalent types of gastrointestinal infections in Germany. METHODS: We analyzed all notifications of laboratory-confirmed or epidemiologically linked gastrointestinal infections due to norovirus, rotavirus, Salmonella species, and Campylobacter species reported to the Robert Koch Institute in Berlin, Germany, from 2002 through 2008. Infections were considered nosocomial if disease onset was more than 2 days after hospitalization for norovirus, rotavirus, and Salmonella infection and more than 5 days after hospitalization for Campylobacter infection. RESULTS: During the study period, 710,725 norovirus, 394,500 rotavirus, 395,736 Salmonella, and 405,234 Campylobacter gastrointestinal infections were reported. Excluding cases for which nosocomial status could not be determined, we identified 39,424 (49%) of 80,650 norovirus, 11,592 (14%) of 83,451 rotavirus, 3,432 (8%) of 43,348 Salmonella, and 645 (2%) of 33,503 Campylobacter gastrointestinal infections as definite nosocomial cases. Multivariate analysis confirmed higher risk of gastrointestinal NIs for patients aged more than 70 years (relative risk [RR], 7.0 [95% confidence interval {CI}, 6.7-7.2]; [Formula: see text]) and residents of western states (RR, 1.3 [95% CI, 1.2-1.3]; [Formula: see text]) and lower risk for female patients (RR, 0.9 [95% CI, 0.9-0.9; [Formula: see text]). Yearly NI proportions remained stable except for norovirus. CONCLUSIONS: The investigated gastrointestinal NIs in Germany do not show a clear trend, but they are at high level, revealing potential for public health action and improvement of hospital infection control mainly among older patients. National prevalence studies on gastrointestinal NIs would be of additional value to give more insight on how and where to improve hospital infection control.

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.

Nasal colonization of humans with methicillin-resistant Staphylococcus aureus (MRSA) CC398 with and without exposure to pigs.

BACKGROUND: Studies in several European countries and in North America revealed a frequent nasal colonization of livestock with MRSA CC398 and also in humans with direct professional exposure to colonized animals. The study presented here addresses the question of further transmission to non exposed humans. METHODS: After selecting 47 farms with colonized pigs in different regions of Germany we sampled the nares of 113 humans working daily with pigs and of their 116 non exposed family members. The same was performed in 18 veterinarians attending pig farms and in 44 of their non exposed family members. For investigating transmission beyond families we samples the nares of 462 pupils attending a secondary school in a high density pig farming area. MRSA were detected by direct culture on selective agar. The isolates were typed by means of spa-sequence typing and classification of SCCmec elements. For attribution of spa sequence types to clonal lineages as defined by multi locus sequence typing we used the BURP algorithm. Antibiotic susceptibility testing was performed by microbroth dilution assay. RESULTS: At the farms investigated 86% of humans exposed and only 4.3% of their family members were found to carry MRSA exhibiting spa-types corresponding to clonal complex CC398. Nasal colonization was also found in 45% of veterinarians caring for pig farms and in 9% of their non exposed family members. Multivariate analysis revealed that antibiotic usage prior to sampling beard no risk with respect to colonization. From 462 pupils only 3 were found colonized, all 3 were living on pig farms. CONCLUSION: These results indicate that so far the dissemination of MRSA CC398 to non exposed humans is infrequent and probably does not reach beyond familial communities.

Automatic outbreak detection algorithm versus electronic reporting system.

To determine efficacy of automatic outbreak detection algorithms (AODAs), we analyzed 3,582 AODA signals and 4,427 reports of outbreaks caused by Campylobacter spp. or norovirus during 2005-2006 in Germany. Local health departments reported local outbreaks with higher sensitivity and positive predictive value than did AODAs.

Staphylococcus aureus in dermatology outpatients with special emphasis on community-associated methicillin-resistant strains.

Methicillin-resistant Staphylococcus aureus (MRSA) emerged as a community-associated pathogen (CA-MRSA) in the past 6 years. This prospective study investigated dermatology outpatients with inflammatory skin diseases, leg ulcers, and skin infections for Panton-Valentine leukocidin (PVL)-positive S. aureus, often associated with deep skin infection. In case of PVL positivity, molecular typing and PCR demonstration of resistance genes were performed. Out of 248 patients, 130 carried S. aureus, 24 being lukS-PV lukF-PV positive. Eighteen were MRSA, 11 of them belonging to the multilocus sequence typing clonal complex (CC)5, 1 to CC45, and 2/18 to CC8. Out of 18 patients, 4 were CA-MRSA containing lukS-PV lukF-PV as an important trait of CA-MRSA. Out of four CA-MRSA isolates, two were of type ST080 containing far-1 coding for fusidic acid (FUS) resistance and two were FUS sensitive (ST152 and ST001). The FUS-sensitive CA-MRSA, which corresponded to the CA-MRSA of ST001 from the United States, was detected in Germany for the first time, indicating that dermatologists are first in line to detect CA-MRSA. In contrast to CA-MRSA from other continents, far-1-coded FUS resistance represents a typical marker for the widespread CA-MRSA ST080 in Europe, especially in Germany. The significant risk factor for the acquisition of CA-MRSA was visits to foreign countries and/or professional or private contacts with foreigners.

Survey on the population's needs and the public health response during floods in Germany 2002.

A survey after the 2002 flood in Germany identifies contact with floodwater as a risk factor for diarrhea and injuries and shows that the affected population valued the given professional support in securing homes and cleanup work. Evacuations were well tolerated. Information reached the population mainly through loudspeakers, radio, and TV.

First international diagnostic accuracy study for the serological detection of West Nile virus infection.

BACKGROUND: The diagnosis of an acute or convalescent West Nile (WN) virus infection can be confirmed by various serological assays such as enzyme immunoassay (EIA), immunofluorescence assay (IFA), or neutralisation test (NT) which are conducted by a growing number of laboratories. However, as the degree of proficiency may vary between laboratories, quality control measures for laboratory diagnostics are essential. METHODS: We have performed an external quality assurance (EQA) programme for the serological detection of WN virus infection to assess the diagnostic quality of laboratories. The participating laboratories received a proficiency panel of 10 coded lyophilised test samples comprising four antisera positive for WN antibodies as positive controls, three antisera positive for antibodies against other heterologous flaviviruses plus one multireactive unspecific serum as specificity controls, and two negative serum samples. RESULTS: Twenty-seven laboratories from 20 different countries in Europe, the Middle East, the Americas and Africa participated in this EQA programme. Applying the proficiency criteria of this study, only eight laboratories correctly analysed all samples with their respective EIA, IFA or NT methods. Eighteen laboratories correctly identified between 77.8 and 90% of the samples, and one laboratory identified only 70% correctly with a clear need to eliminate cross-reactivity with other antisera, particularly those elicited by yellow fever virus. Differentiation between the results for IgM and IgG was considered separately and revealed that IgM-antibodies were detected less frequently than IgG-antibodies (p < 0.001). However, the assay used was not a significant technical factor influencing laboratory performance. CONCLUSION: The EQA programme provides information on the quality of different serological assays used by the participating laboratories and indicates that most need to improve their assays, in particular to avoid cross-reactions with antibodies to heterologous flaviviruses.

SurvNet electronic surveillance system for infectious disease outbreaks, Germany.

In 2001, the Robert Koch Institute (RKI) implemented a new electronic surveillance system (SurvNet) for infectious disease outbreaks in Germany. SurvNet has captured 30,578 outbreak reports in 2001-2005. The size of the outbreaks ranged from 2 to 527 cases. For outbreaks reported in 2002-2005, the median duration from notification of the first case to the local health department until receipt of the outbreak report at RKI was 7 days. Median outbreak duration ranged from 1 day (caused by Campylobacter) up to 73 days (caused by Mycobacterium tuberculosis). The most common settings among the 10,008 entries for 9,946 outbreaks in 2004 and 2005 were households (5,262; 53%), nursing homes (1,218; 12%), and hospitals (1,248; 12%). SurvNet may be a useful tool for other outbreak surveillance systems because it minimizes the workload of local health departments and captures outbreaks even when causative pathogens have not yet been identified.

Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology.

BACKGROUND: Case definitions have been recognized to be important elements of public health surveillance systems. They are to assure comparability and consistency of surveillance data and have crucial impact on the sensitivity and the positive predictive value of a surveillance system. The reliability of case definitions has rarely been investigated systematically. METHODS: We conducted a Round-Robin test by asking all 425 local health departments (LHD) and the 16 state health departments (SHD) in Germany to classify a selection of 68 case examples using case definitions. By multivariate analysis we investigated factors linked to classification agreement with a gold standard, which was defined by an expert panel. RESULTS: A total of 7870 classifications were done by 396 LHD (93%) and all SHD. Reporting sensitivity was 90.0%, positive predictive value 76.6%. Polio case examples had the lowest reporting precision, salmonellosis case examples the highest (OR = 0.008; CI: 0.005-0.013). Case definitions with a check-list format of clinical criteria resulted in higher reporting precision than case definitions with a narrative description (OR = 3.08; CI: 2.47-3.83). Reporting precision was higher among SHD compared to LHD (OR = 1.52; CI: 1.14-2.02). CONCLUSION: Our findings led to a systematic revision of the German case definitions and build the basis for general recommendations for the creation of case definitions. These include, among others, that testable yes/no criteria in a check-list format is likely to improve reliability, and that software used for data transmission should be designed in strict accordance with the case definitions. The findings of this study are largely applicable to case definitions in many other countries or international networks as they share the same structural and editorial characteristics of the case definitions evaluated in this study before their revision.

Chemoprophylaxis and malaria death rates.

To determine the effect of chemoprophylaxis on the case-fatality rate of malaria, we analyzed all cases of Plasmodium falciparum malaria in nonimmune persons reported from 1993 to 2004 in Germany. In univariate and multivariate logistic regression analysis, we determined the effect of age, sex, chemoprophylaxis, chemoprophylactic regimen, compliance for chemoprophylactic regimen, exposure prophylaxis, country of infection, and year of reporting on the outcome. Of 3,935 case-patients, 116 (3%) died of malaria. Univariate analysis showed significant associations with death for chemoprophylaxis with chloroquine plus proguanil compared to no chemoprophylaxis. The multivariate model showed that patients who had taken chemoprophylaxis were less likely to die compared to those who had not taken chemoprophylaxis, adjusted for patient age and reporting year. The study demonstrated that chemoprophylaxis significantly reduced fatality rates among nonimmune malaria patients and supports the importance of existing guidelines for malaria prevention.