The gut microbiome, resistome, and mycobiome in preterm newborn infants and mouse pups: lack of lasting effects by antimicrobial therapy or probiotic prophylaxis.

BACKGROUND: Enhancing our understanding of the underlying influences of medical interventions on the microbiome, resistome and mycobiome of preterm born infants holds significant potential for advancing infection prevention and treatment strategies. We conducted a prospective quasi-intervention study to better understand how antibiotics, and probiotics, and other medical factors influence the gut development of preterm infants. A controlled neonatal mice model was conducted in parallel, designed to closely reflect and predict exposures. Preterm infants and neonatal mice were stratified into four groups: antibiotics only, probiotics only, antibiotics followed by probiotics, and none of these interventions. Stool samples from both preterm infants and neonatal mice were collected at varying time points and analyzed by 16 S rRNA amplicon sequencing, ITS amplicon sequencing and whole genome shotgun sequencing. RESULTS: The human infant microbiomes showed an unexpectedly high degree of heterogeneity. Little impact from medical exposure (antibiotics/probiotics) was observed on the strain patterns, however, Bifidobacterium bifidum was found more abundant after exposure to probiotics, regardless of prior antibiotic administration. Twenty-seven antibiotic resistant genes were identified in the resistome. High intra-variability was evident within the different treatment groups. Lastly, we found significant effects of antibiotics and probiotics on the mycobiome but not on the microbiome and resistome of preterm infants. CONCLUSIONS: Although our analyses showed transient effects, these results provide positive motivation to continue the research on the effects of medical interventions on the microbiome, resistome and mycobiome of preterm infants.

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.

Antimicrobial Resistance and the Spectrum of Pathogens in Dental and Oral-Maxillofacial Infections in Hospitals and Dental Practices in Germany.

Data on microbiological profiles in odontogenic infections are scarce. This study aimed to analyze the spectrum of pathogens and antimicrobial resistance in clinical isolates from dental and oral-maxillofacial clinical settings in Germany. We analyzed 20,645 clinical isolates (dental practices: n = 5,733; hospitals: n = 14,912) from patients with odontogenic infections using data (2012-2019) from the German Antimicrobial-Resistance-Surveillance (ARS) system. A total of 224 different species from 73 genera were found in clinical isolates from dental practices, and 329 different species from 97 genera were identified in isolates from hospital patients. In both hospitals and dental practices Streptococcus spp. (33 and 36%, respectively) and Staphylococcus spp. (21 and 12%, respectively) were the most frequently isolated microorganisms. In Streptococcus spp. isolates from hospitals, penicillin and aminopenicillin resistance proportions were 8.0% (95%CI 4.7-14.9%) and 6.9% (95%CI 4.7-9.9%), respectively. Substantially lower resistance proportions of penicillin and aminopenicillin were observed in dental practices [2.6% (95%CI 1.4-4.7%) and 2.1% (95%CI 1.1-4.0%), respectively]. Among Staphylococcus aureus isolates from hospital patients methicillin resistance proportions were 12.0% (95%CI 9.7-14.8%), which was higher than in isolates from dental practices (5.8% (95%CI 4.1-8.1%)]. High clindamycin and macrolide resistance proportions (>17%) were observed in Streptococcus spp. and Staphylococcus aureus isolates. In Klebsiella spp. isolates carbapenem resistance proportions were <1%. In sum, substantial antibiotic resistance was observed in isolates from odontogenic infections, which calls for strengthened efforts in antibiotic stewardship and infection prevention and control measures in both hospitals and dental practices.

Bugs That Can Resist Antibiotics but Not Men: Gender-Specific Differences in Notified Infections and Colonisations in Germany, 2010-2019.

Data from surveillance networks show that men have a higher incidence rate of infections with anti-microbial-resistant (AMR) pathogens than women. We systematically analysed data of infections and colonisations with AMR pathogens under mandatory surveillance in Germany to quantify gender-specific differences. We calculated incidence-rates (IR) per 100,000 person-years for invasive infections with Methicillin-resistant Staphylococcus aureus (MRSA), and for infections or colonisations with carbapenem-non-susceptible Acinetobacter spp. (CRA), and Enterobacterales (CRE), using the entire German population as a denominator. We limited the study periods to years with complete notification data (MRSA: 2010-2019, CRA/CRE: 2017-2019). We used Poisson regression to adjust for gender, age group, federal state, and year of notification. In the study periods, IR for all notifications were 4.2 for MRSA, 0.90 for CRA, and 4.8 for CRE per 100,000 person--years. The adjusted IR ratio for infections of men compared to women was 2.3 (95% confidence interval [CI]: 2.2-2.3) for MRSA, 2.2 (95%CI: 1.9-2.7) for CRA, and 1.7 (95%CI: 1.6-1.8) for CRE. Men in Germany show about double the risk for infection with AMR pathogens than women. This was also true for colonisations, where data were available. Screening procedures and associated hygiene measures may profit from a gender-stratified approach.

[Recording of SARS-CoV-2 laboratory tests in Germany]. / Erfassung der Labortestungen auf SARS-CoV-2 in Deutschland.

The collection of data on SARS-CoV­2 tests is central to the assessment of the infection rate in the context of the COVID-19 pandemic. At the Robert Koch Institute (RKI), data collected from various laboratory data recording systems are consolidated. First, this article aims to exemplify significant aspects regarding test procedures. Subsequently the different systems for recording laboratory tests are described and test numbers from the RKI test laboratory query and the laboratory-based SARS-CoV­2 surveillance as well as accounting data from the Association of Statutory Health Insurance Physicians for SARS-CoV­2 laboratory tests are shown.Early in the pandemic, the RKI test laboratory query and the laboratory-based SARS-CoV­2 surveillance became available and able to evaluate data on performed tests and test capacities. By recording the positive and negative test results, statements about the total number of tests and the proportion of positive test rates can be made. While the aggregate test numbers are largely representative nationwide, they are not always representative at the state and district level. The billing data of the Association of Statutory Health Insurance Physicians can complement the laboratory data afterwards. In addition, it can provide a retrospective assessment of the total number of SARS-CoV­2 numbers in Germany, because the services provided by statutory health insurers (around 85% of the population in Germany) are included. The various laboratory data recording systems complement one another and the evaluations flow into the recommended measures for the pandemic response.

[Prevalence of multiresistant gram-negative bacteria in inhabitants of long-term care facilities in 2019 in Thuringia]. / Prävalenz von multiresistenten gramnegativen Erregern bei Bewohnern von stationären Pflegeeinrichtungen 2019 in Thüringen.

BACKGROUND: Multidrug-resistant gram-negative bacteria (MDRGN) pose an emerging threat in German hospitals and in the outpatient sector. However, only few studies have investigated the prevalence of MDRGN in nonhospital settings and the associated risk factors for colonization. OBJECTIVE: In our study we determined the prevalence of MDRGN in inhabitants of long-term care facilities (LTCFs) and associated risk factors for colonization in the region Weimar, Weimarer Land, and Jena. METHODS: Between May and August 2019, deep rectal swabs were taken from 307 inhabitants of 13 facilities and examined microbiologically for the presence of MDRGN. Furthermore, using a standardized questionnaire, the characteristics of the inhabitants were collected and their association with the likelihood for colonization with MDRGN was analyzed. RESULTS: MDRGN were found in 59 swabs, predominantly Escherichia coli (95%). The weighted prevalence of extended spectrum beta-lactamase-producing bacteria was 19.1% and for MDRGN with additional resistances to fluoroquinolones was 12.3%. Resistances to carbapenems or carbapenemases were not found. Multivariable as well as univariable analysis recognized the presence of chronic wounds to be a potential risk factor (OR: 2,66 [95 %-CI: 1,54-4,60]). Additionally, the univariable analysis detected the necessity of a wheelchair and the accommodation in double rooms as risk factors. DISCUSSION: The prevalence of MDRGN found in our study is similar to findings of previous German studies. The result shows the importance of strict compliance with basic hygiene guidelines for all inhabitants of LTCFs for the prevention of transmission of MDRGN.

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.

The ongoing challenge of vancomycin-resistant Enterococcus faecium and Enterococcus faecalis in Europe: an epidemiological analysis of bloodstream infections.

Vancomycin-resistant enterococci infections are of great public health significance due to limited therapeutic options. We investigated epidemiological trends and risk factors of vancomycin resistance in enterococci isolates from patients with bloodstream infections in the EU/EEA from 2012 to 2018. Routine vancomycin susceptibility data of clinical E. faecium (n = 67,022) and E. faecalis (n = 103,112) blood isolates from the European Antimicrobial Resistance Surveillance Network were analysed using descriptive statistics and multivariable regression analyses. In Europe, proportions of vancomycin-resistant E. faecium (VREFm) increased from 8.1% (95%CI 6.7-9.7%) in 2012 to 19.0% (95%CI 16.8-21.5%) in 2018. Rising VREFm proportions were observed across all European regions, both genders and all age groups except children and adolescents (1-19 years). Adults (20-59 years) and elderly (≥60 years) had an increased likelihood of VREFm compared to children and adolescents (1-19 years) (OR: 1.99 [95%CI 1.42-2.79, p < 0.001] and OR: 1.56 [95%CI 1.09-2.23, p = 0.014], respectively). Inpatients hospital units, including internal medicine and ICUs, were associated with an increased likelihood of VREFm (OR: 2.29 (95%CI 1.58-3.32, p < 0.001) compared to the emergency department which reflects patients with community origin of E. faecium infections. The mean proportion of vancomycin-resistant E. faecalis in Europe was found to be low (1.1% [95%CI 0.9-1.4%]). Local and regional authorities should intensify efforts directed at diagnostic and antimicrobial stewardship for vancomycin and all last resort drugs for the management of VREFm, particularly for hospitalized elderly patients.

The rise in vancomycin-resistant Enterococcus faecium in Germany: data from the German Antimicrobial Resistance Surveillance (ARS).

Background: Due to limited therapeutic options, vancomycin-resistant Enterococcus faecium (VREF) is of great clinical significance. Recently, rising proportions of vancomycin resistance in enterococcal infections have been reported worldwide. This study aims to describe current epidemiological trends of VREF in German hospitals and to identify factors that are associated with an increased likelihood of vancomycin resistance in clinical E. faecium isolates. Methods: 2012 to 2017 data from routine vancomycin susceptibility testing of 35,906 clinical E. faecium isolates from 148 hospitals were analysed using data from the German Antimicrobial Resistance Surveillance System. Descriptive statistical analyses and uni- and multivariable regression analyses were performed to investigate the impact of variables, such as year of sampling, age and region, on vancomycin resistance in clinical E. faecium isolates. Results: From 2014 onwards the proportions of clinical E. faecium isolates exhibiting resistance to vancomycin increased from 11.2% (95% confidence interval [CI] 9.4-13.3%) to 26.1% (95% CI 23.1-29.4%) in 2017. The rise of VREF proportions is primarily observed in the southern regions of Germany, whereas northern regions do not show a major increase. In the Southwest and Southeast, VREF proportions increased from 10.8% (95% CI 6.9-16.5%) and 3.8% (95% CI 3.0-11.5%) in 2014 to 36.7% (95% CI 32.9-40.8%) and 36.8% (95% CI 29.2-44.7%) in 2017, respectively. VREF proportions were considerably higher in isolates from patients aged 40-59 years compared to younger patients. Further regression analyses show that in relation to secondary care hospitals, E. faecium samples collected in specialist care hospitals and prevention and rehabilitation care centres are more likely to be vancomycin-resistant (odds ratios: 2.4 [95% CI 1.2-4.6] and 2.4 [95% CI 1.9-3.0], respectively). No differences in VREF proportions were found between female and male patients as well as between different clinical specimens. Conclusion: The proportion of VREF is increasing in German hospitals, particularly in southern regions in Germany. Increased efforts in infection control and antibiotic stewardship activities accounting for local resistance patterns are necessary to combat the spread of VREF in Germany.

Genome-based analysis of Carbapenemase-producing Klebsiella pneumoniae isolates from German hospital patients, 2008-2014.

Background: By using whole genome sequence data we aimed at describing a population snapshot of carbapenemase-producing K. pneumoniae isolated from hospitalized patients in Germany between 2008 and 2014. Methods: We selected a representative subset of 107 carbapenemase-producing K. pneumoniae clinical isolates possessing the four most prevalent carbapenemase types in Germany (KPC-2, KPC-3, OXA-48, NDM-1). Isolates were processed via illumina NGS. Data were analysed using different SNP-based mapping and de-novo assembly approaches. Relevant information was extracted from NGS data (antibiotic resistance determinants, wzi gene/cps type, virulence genes). NGS data from the present study were also compared with 238 genome data from two previous international studies on K. pneumoniae. Results: NGS-based analyses revealed a preferred prevalence of KPC-2-producing ST258 and KPC-3-producing ST512 isolates. OXA-48, being the most prevalent carbapenemase type in Germany, was associated with various K. pneumoniae strain types; most of them possessing IncL/M plasmid replicons suggesting a preferred dissemination of blaOXA-48 via this well-known plasmid type. Clusters ST15, ST147, ST258, and ST512 demonstrated an intermingled subset structure consisting of German and other European K. pneumoniae isolates. ST23 being the most frequent MLST type in Asia was found only once in Germany. This latter isolate contained an almost complete set of virulence genes and a K1 capsule suggesting occurrence of a hypervirulent ST23 strain producing OXA-48 in Germany. Conclusions: Our study results suggest prevalence of "classical" K. pneumonaie strain types associated with widely distributed carbapenemase genes such as ST258/KPC-2 or ST512/KPC-3 also in Germany. The finding of a supposed hypervirulent and OXA-48-producing ST23 K. pneumoniae isolates outside Asia is highly worrisome and requires intense molecular surveillance.

Exploring the effect of previous inactivated influenza vaccination on seasonal influenza vaccine effectiveness against medically attended influenza: Results of the European I-MOVE multicentre test-negative case-control study, 2011/2012-2016/2017.

BACKGROUND: Results of previous influenza vaccination effects on current season influenza vaccine effectiveness (VE) are inconsistent. OBJECTIVES: To explore previous influenza vaccination effects on current season VE among population targeted for vaccination. METHODS: We used 2011/2012 to 2016/2017 I-MOVE primary care multicentre test-negative data. For each season, we compared current season adjusted VE (aVE) between individuals vaccinated and unvaccinated in previous season. Using unvaccinated in both seasons as a reference, we then compared aVE between vaccinated in both seasons, current only, and previous only. RESULTS: We included 941, 2645 and 959 influenza-like illness patients positive for influenza A(H1N1)pdm09, A(H3N2) and B, respectively, and 5532 controls. In 2011/2012, 2014/2015 and 2016/2017, A(H3N2) aVE point estimates among those vaccinated in previous season were -68%, -21% and -19%, respectively; among unvaccinated in previous season, these were 33%, 48% and 46%, respectively (aVE not computable for influenza A(H1N1)pdm09 and B). Compared to current season vaccination only, VE for both seasons' vaccination was (i) similar in two of four seasons for A(H3N2) (absolute difference [ad] 6% and 8%); (ii) lower in three of four seasons for influenza A(H1N1)pdm09 (ad 18%, 26% and 29%), in two seasons for influenza A(H3N2) (ad 27% and 39%) and in two of three seasons for influenza B (ad 26% and 37%); (iii) higher in one season for influenza A(H1N1)pdm09 (ad 20%) and influenza B (ad 24%). CONCLUSIONS: We did not identify any pattern of previous influenza vaccination effect. Prospective cohort studies documenting influenza infections, vaccinations and vaccine types are needed to understand previous influenza vaccinations' effects.

2015/16 I-MOVE/I-MOVE+ multicentre case-control study in Europe: Moderate vaccine effectiveness estimates against influenza A(H1N1)pdm09 and low estimates against lineage-mismatched influenza B among children.

BACKGROUND: During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine. METHODS: We used the test-negative design in a multicentre case-control study in twelve European countries to measure 2015/16 influenza vaccine effectiveness (VE) against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed a systematic sample of consulting ILI patients and a random sample of influenza-positive swabs was sequenced. We calculated adjusted VE against influenza A(H1N1)pdm09, A(H1N1)pdm09 genetic group 6B.1 and influenza B overall and by age group. RESULTS: We included 11 430 ILI patients, of which 2272 were influenza A(H1N1)pdm09 and 2901 were influenza B cases. Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5-46.7). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: -32.3 to 65.0), 41.4% (95% CI: 20.5-56.7) and 13.2% (95% CI: -38.0 to 45.3), respectively. Overall VE against influenza A(H1N1)pdm09 genetic group 6B.1 was 32.8% (95% CI: -4.1 to 56.7). Among those aged 0-14, 15-64 and ≥65 years, VE against influenza B was -47.6% (95% CI: -124.9 to 3.1), 27.3% (95% CI: -4.6 to 49.4) and 9.3% (95% CI: -44.1 to 42.9), respectively. CONCLUSIONS: Vaccine effectiveness (VE) against influenza A(H1N1)pdm09 and its genetic group 6B.1 was moderate in children and adults, and low among individuals ≥65 years. Vaccine effectiveness (VE) against influenza B was low and heterogeneous among age groups. More information on effects of previous vaccination and previous infection is needed to understand the VE results against influenza B in the context of a mismatched vaccine.

Treatment outcome in children with nontuberculous mycobacterial lymphadenitis: A retrospective follow-up study.

INTRODUCTION: Information on the long-term treatment outcome following nontuberculous mycobacterial (NTM) lymphadenitis is very limited. We performed a study to (a) compare cure rates following different initial treatment courses, (b) describe subsequent treatment courses and their outcomes, and (c) determine the occurrence of late sequelae in immunocompetent children with NTM lymphadenitis. MATERIALS AND METHODS: In 2011, we conducted a retrospective follow-up study in 71 parents whose children had been hospitalized with NTM disease 2002-2005. A telephone survey was performed using a standardized questionnaire to collect information on the therapeutic management and treatment outcome. RESULTS: Of 61 children with NTM lymphadenitis, 33 (54%) children were cured after the initial treatment. We found no significant difference in cure rates following surgical intervention only (45%, 13/29 children) and a combination of surgical intervention and chemotherapy (61%, 19/31 children). In 7 out of 11 children, the cure rate following complete lymph node excision was 64%. Subsequent courses of treatment including repeated surgical intervention, combination therapy, chemotherapy only, and wait-and-see strategy in children where initial therapy failed resulted in the cure of all 61 children. In four children (7%), recurrences were observed up to 5 years later. CONCLUSIONS: Our study showed that recurrent NTM lymphadenitis might be observed several years after initial resolution of disease. The cure rate following complete lymph node excision was lower than reported in other studies. Subsequent treatment courses were necessary in half of the children. Physicians and parents need to be aware that NTM lymphadenitis in children requires careful choice of intervention and active follow-up.

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.

Vaccine effectiveness in preventing laboratory-confirmed influenza in primary care patients in a season of co-circulation of influenza A(H1N1)pdm09, B and drifted A(H3N2), I-MOVE Multicentre Case-Control Study, Europe 2014/15.

Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2014/15. We undertook a multicentre case-control study in eight European countries to measure 2014/15 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed all or a systematic sample of ILI patients. We compared the odds of vaccination of ILI influenza positive patients to negative patients. We calculated adjusted VE by influenza type/subtype, and age group. Among 6,579 ILI patients included, 1,828 were A(H3N2), 539 A(H1N1)pdm09 and 1,038 B. VE against A(H3N2) was 14.4% (95% confidence interval (CI): -6.3 to 31.0) overall, 20.7% (95%CI: -22.3 to 48.5), 10.9% (95%CI -30.8 to 39.3) and 15.8% (95% CI: -20.2 to 41.0) among those aged 0-14, 15-59 and  ≥60 years, respectively. VE against A(H1N1)pdm09 was 54.2% (95%CI: 31.2 to 69.6) overall, 73.1% (95%CI: 39.6 to 88.1), 59.7% (95%CI: 10.9 to 81.8), and 22.4% (95%CI: -44.4 to 58.4) among those aged 0-14, 15-59 and  ≥60 years respectively. VE against B was 48.0% (95%CI: 28.9 to 61.9) overall, 62.1% (95%CI: 14.9 to 83.1), 41.4% (95%CI: 6.2 to 63.4) and 50.4% (95%CI: 14.6 to 71.2) among those aged 0-14, 15-59 and ≥60 years respectively. VE against A(H1N1)pdm09 and B was moderate. The low VE against A(H3N2) is consistent with the reported mismatch between circulating and vaccine strains.

[Influenza pandemic deaths in Germany from 1918 to 2009. Estimates based on literature and own calculations]. / Todesfälle durch Influenzapandemien in Deutschland 1918 bis 2009. Schätzwerte auf Basis der Literatur und ergänzende eigene Berechnungen.

BACKGROUND AND OBJECTIVE: Estimation of the number of deaths as a consequence of the influenza pandemics in the twentieth and twenty-first centuries (i.e. 1918-1919, 1957-1958, 1968-1970 and 2009) is a challenge worldwide and also in Germany. After conducting a systematic literature search complemented by our own calculations, values and estimates for all four pandemics were collated and evaluated. METHOD: A systematic literature search including the terms death, mortality, pandemic, epidemic, Germany, 1918, 1957, 1968, 2009 was performed. Hits were reviewed by title and abstract and selected for possible relevance. We derived our own estimates using excess mortality calculations, which estimate the mortality exceeding that to be expected. All identified values were evaluated by methodology and quality of the database. Numbers of pandemic deaths were used to calculate case fatality rates and were compared with global values provided by the World Health Organization. RESULTS: For the pandemic 1918-1919 we identified 5 relevant publications, 3 for the pandemics 1957-1958 and 1968-1970 and 3 for 2009. For all four pandemics the most plausible estimations were based on time series analyses, taken either from the literature or from our own calculations based on monthly or weekly all cause death statistics. For the four pandemics these estimates were in chronological order 426,600 (1918-1919), 29,100 (1957-1958), 46,900 (1968-1970) and 350 (2009) excess pandemic-related deaths. This translates to an excess mortality ranging between 691 per 100,000 (0.69 % in 1918-1919) and 0.43 per 100,000 (0.00043 % in 2009). Case fatality rates showed good agreement with global estimates. CONCLUSION: We have proposed plausible estimates of pandemic-related excess number of deaths for the last four pandemics as well as excess mortality in Germany. The heterogeneity among pandemics is large with a variation factor of more than 1000. Possible explanations include characteristics of the virus or host (immunity), social conditions, status of the healthcare system and medical advances.

Antiviral Medications in Seasonal and Pandemic Influenza.

BACKGROUND: Amantadine, oseltamivir, and zanamivir are currently available in Germany for the prevention and treatment of influenza. We review their efficacy and side-effect profiles. METHODS: This review is based on pertinent randomized and controlled trials (RCTs) and systematic reviews retrieved by a systematic literature search, and on other relevant literature. RESULTS: The efficacy of antiviral drugs for the prevention of symptomatic influenza ranges from 60% to 90% (number needed to treat [NNT], 8-89) depending on the population and type of drug in question. Antiviral drugs shorten the duration of illness by 0.5-1.5 days when given within 48 hours of the onset of symptoms. Neuraminidase inhibitors do not significantly lower the incidence of bronchitis in adults, or of otitis media in children; they do have a positive effect against reported, but not necessarily diagnostically confirmed pneumonia in adults (NNT, 89 [50-232]). The RCTs yielded no information about possible effects on severe cases of influenza, or on mortality, as they included only mildly or moderately ill patients, but observational studies have yielded some evidence of benefit. The most common side effects of oseltamivir (>10%) are headache, nausea, and vomiting; of zanamivir (>1%), a skin rash; and of amantadine (>1%), loss of appetite, nausea, and central nervous effects. CONCLUSION: The benefits of antiviral drugs, particularly neuraminidase inhibitors, outweigh their risks. In deciding whether to use them, physicians should consider the properties of the currently circulating viruses and the patient's individual risk constellation, as directed in clinical treatment recommendations.

The European I-MOVE Multicentre 2013-2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2).

BACKGROUND: In the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013-2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013-2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season. METHODS: Practitioners systematically selected ILI patients to swab within eight days of symptom onset. We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I(2) index and Cochrane's Q test. If the I(2) was <50%, we estimated pooled VE as (1 minus the OR)×100 using a one-stage model with study site as a fixed effect. If the I(2) was >49% we used a two-stage random effects model. RESULTS: We included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p=0.695) and the I(2) index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4-67.0). For A(H3N2), the I(2) was 51.5% (p=0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: -34.4-63.2). CONCLUSIONS: The results suggest a moderate 2013-2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses.

Contact investigation for imported case of Middle East respiratory syndrome, Germany.

On March 19, 2013, a patient from United Arab Emirates who had severe respiratory infection was transferred to a hospital in Germany, 11 days after symptom onset. Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) was suspected on March 21 and confirmed on March 23; the patient, who had contact with an ill camel shortly before symptom onset, died on March 26. A contact investigation was initiated to identify possible person-to-person transmission and assess infection control measures. Of 83 identified contacts, 81 were available for follow-up. Ten contacts experienced mild symptoms, but test results for respiratory and serum samples were negative for MERS-CoV. Serologic testing was done for 53 (75%) of 71 nonsymptomatic contacts; all results were negative. Among contacts, the use of FFP2/FFP3 face masks during aerosol exposure was more frequent after MERS-CoV infection was suspected than before. Infection control measures may have prevented nosocomial transmission of the virus.