Marked Underreporting of Pertussis Requiring Hospitalization in Infants as Estimated by Capture-Recapture Methodology, Germany, 2013-2015

Background: In Germany, pertussis became notifiable in eastern federal states in 2002 and nationwide in March 2013. Infants are at greatest risk for severe disease, with a high proportion requiring hospitalization. We implemented enhanced hospital-based surveillance to estimate the incidence of pertussis requiring hospitalization among infants in Germany and to determine the proportion of infants hospitalized with pertussis too young to have been vaccinated. Methods: Enhanced surveillance was implemented within a nationwide hospital surveillance network (ESPED). We defined cases as children less than 1 year of age hospitalized due to laboratory-confirmed pertussis with disease onset from 01/07/2013-30/06/2015. We matched cases to those ascertained in the national statutory notification system, and estimated incidence using capture-recapture methodology. Results: The estimated annual incidence of pertussis requiring hospitalization in infants was 52/100,000 infants (95% confidence interval [CI] 48-57/100,000), with 39% under-reporting to the national notification system. During the two epidemiologic years under-reporting decreased from 46% to 32% and was lower in eastern than western federal states (21% vs. 40%). Within ESPED, 154 of 240 infants (64%) were younger than or still at the age recommended for the first vaccine dose;55 (23%) could have received one or more vaccine doses. Median length of hospitalization was 9 days (IQR 5-13 days) and 18% required intensive care treatment. Conclusions: Our study revealed a high burden of pertussis in infants with marked under-reporting, especially in western federal states where notification was only recently established. Strategies for the prevention of severe pertussis

Lessons Learned from an Outbreak in Germany, 2012-2013

Background We undertook investigations in response to an invasive meningococcal disease (IMD) outbreak in men who have sex with men (MSM) in Berlin 2012–2013 to better understand meningococcal transmission and IMD risk in MSM. Methods We retrospectively searched for further IMD cases in MSM in Germany through local health departments and undertook exploratory interviews. We performed antigen sequence typing, characterized fHbp and aniA genes of strains with the outbreak finetype and reviewed epidemiologically or spatiotemporally linked cases from 2002–2014. Results Among the 148 IMD-cases notified from 01.01.2012–30.09.2013 in 18–59 year-old men we identified 13 MSM in 6 federal states: 11 serogroup C (MenC, all finetype C:P1.5–1,10–8:F3-6), 2 MenB. Interviews with 7 MSM revealed frequent meeting of multiple partners online or via mobile apps and illicit drug use as potential risk factors. MenC incidence was 13-fold higher in MSM than non-MSM. MenC isolates from 9/11 MSM had a novel fHbp allele 766. All C:P1.5–1,10–8:F3-6 strains from MSM versus 16/23 from non-MSM had intact aniA genes (p = 0.04). Although definitive evidence for transmission among MSM in epidemiological or spatiotemporal clusters in 2002–2014 was lacking, clusters were more frequent in men aged 20–49 years. Molecular analysis of C:P1.5–1,10–8:F3-6 strains revealed cases with intact aniA since 2007, mainly associated with fHbp361, fHbp766 and fHbp813, all involving one or more MSM. Conclusions MenC incidence was elevated in MSM during the study period. Multiple casual sexual contacts and illicit drug use were common in affected MSM. In all strains from MSM we detected an intact aniA gene coding for a nitrite reductase, which permits survival in microanaerobic environments and could play a role in meningococcal transmission in MSM through urogenital colonization. Furthermore, meningococcal transmission among MSM may be sustained over large areas and thus require modified spatiotemporal scanning algorithms for timely detection and control

Spatiotemporal Analysis of Invasive Meningococcal Disease, Germany

Meningococcal disease clustering was found by DNA sequence–based finetyping and cluster detection software

Strong Public Health Recommendations from Weak Evidence? Lessons Learned in Developing Guidance on the Public Health Management of Meningococcal Disease.

The evidence underpinning public health policy is often of low quality, leading to inconsistencies in recommended interventions. One example is the divergence in national policies across Europe for managing contacts of invasive meningococcal disease. Aiming to develop consistent guidance at the European level, a group of experts reviewed the literature and formulated recommendations. The group defined eight priority research questions, searched the literature, and formulated recommendations using GRADE methodology. Five of the research questions are discussed in this paper. After taking into account quality of evidence, benefit, harm, value, preference, burden on patient of the intervention, and resource implications, we made four strong recommendations and five weak recommendations for intervention. Strong recommendations related not only to one question with very low quality of evidence as well as to two questions with moderate to high quality of evidence. The weak recommendations related to two questions with low and very low quality of evidence but also to one question with moderate quality of evidence. GRADE methodology ensures a transparent process and explicit recognition of additional factors that should be considered when making recommendations for policy. This approach can be usefully applied to many areas of public health policy where evidence quality is often low

Strong Public Health Recommendations from Weak Evidence? Lessons Learned in Developing Guidance on the Public Health Management of Meningococcal Disease

The evidence underpinning public health policy is often of low quality, leading to inconsistencies in recommended interventions. One example is the divergence in national policies across Europe for managing contacts of invasive meningococcal disease. Aiming to develop consistent guidance at the European level, a group of experts reviewed the literature and formulated recommendations. The group defined eight priority research questions, searched the literature, and formulated recommendations using GRADE methodology. Five of the research questions are discussed in this paper. After taking into account quality of evidence, benefit, harm, value, preference, burden on patient of the intervention, and resource implications, we made four strong recommendations and five weak recommendations for intervention. Strong recommendations related not only to one question with very low quality of evidence as well as to two questions with moderate to high quality of evidence. The weak recommendations related to two questions with low and very low quality of evidence but also to one question with moderate quality of evidence. GRADE methodology ensures a transparent process and explicit recognition of additional factors that should be considered when making recommendations for policy. This approach can be usefully applied to many areas of public health policy where evidence quality is often low

Geo-Spatial Characteristics of 567 Places of Tick-Borne Encephalitis Infection in Southern Germany, 2018–2020

Tick-borne encephalitis (TBE) is a growing public health problem with increasing incidence and expanding risk areas. Improved prevention requires better understanding of the spatial distribution and ecological determinants of TBE transmission. However, a TBE risk map at sub-district level is still missing for Germany. We investigated the distribution and geo-spatial characteristics of 567 self-reported places of probable TBE infection (POI) from 359 cases notified in 2018–2020 in the study area of Bavaria and Baden-Wuerttemberg, compared to 41 confirmed TBE foci and 1701 random comparator places. We built an ecological niche model to interpolate TBE risk to the entire study area. POI were distributed heterogeneously at sub-district level, as predicted probabilities varied markedly across regions (range 0–93%). POI were spatially associated with abiotic, biotic, and anthropogenic geo-spatial characteristics, including summer precipitation, population density, and annual frost days. The model performed with 69% sensitivity and 63% specificity at an optimised probability threshold (0.28) and an area under the curve of 0.73. We observed high predictive probabilities in small-scale areas, consistent with the known circulation of the TBE virus in spatially restricted microfoci. Supported by further field work, our findings may help identify new TBE foci. Our fine-grained risk map could supplement targeted prevention in risk areas.Peer Reviewe

A cluster of invasive meningococcal disease in young men who have sex with men in Berlin, October 2012 to May 2013

Between October 2012 and May 2013, five cases of invasive meningococcal disease in young men who have sex with men (MSM) living in Berlin were notified to local health authorities in Germany. Three of the five cases died. All were caused by serogroup C variants with the finetype P1.5-1,10-8:F3-6. Awareness was increased through the use of community networks; an extension of the existing vaccination recommendation to all MSM is currently being considered

Tick-Borne Encephalitis Risk Increases with Dog Ownership, Frequent Walks, and Gardening: A Case-Control Study in Germany 2018–2020

In Germany, tick-borne encephalitis (TBE) infections mainly occur in southern regions. Despite recent increases in incidence, TBE vaccination coverage remains low, necessitating additional preventive strategies against TBE. Our case-control study in Southern Germany from 2018 to 2020 mapped knowledge/application of tick-protective strategies and identified TBE risk factors. We calculated odds ratios (OR), with 95% confidence intervals (CI). We interviewed 581 cases and 975 matched controls. Most participants recalled lifetime tick bites, mainly while walking, gardening, or hiking. However, only 45% of cases noticed ticks during exposure time; another 12% reported unpasteurized milk intake. While tick-protection knowledge was satisfactory, application lagged behind. Risk factors included dog ownership (OR = 2.45, 95% CI: 1.85–3.24), walks ≥ 4×/week (OR = 2.11, 95% CI: 1.42–3.12), gardening ≥ 4×/week (OR = 1.83, 95% CI: 1.11–3.02), and garden proximity < 250 m of forests (OR = 2.54, 95% CI: 1.82–3.56). Applying ≥2 tick-protective strategies (OR = 0.52, 95% CI: 0.40–0.68) and keeping lawns mowed (OR = 0.63, 95% CI: 0.43–0.91) were inversely associated with TBE. In 2020 (likely pandemic-related), cases reported significantly more walks than previously, potentially explaining the record high case numbers. Our findings provide guidance on targets for TBE prevention. Persons with gardens near forests, frequent outdoor activities, or dogs could particularly benefit from targeted information, including on vaccination and preventing tick bites.Peer Reviewe

Epidemiological impact and cost-effectiveness of universal vaccination with Bexsero(®) to reduce meningococcal group B disease in Germany.

Bexsero, a new vaccine against serogroup B meningococcal disease (MenB), was licensed in Europe in January 2013. In Germany, Bexsero is recommended for persons at increased risk of invasive meningococcal disease, but not for universal childhood vaccination. To support decision making we adapted the independently developed model for England to the German setting to predict the potential health impact and cost-effectiveness of universal vaccination with Bexsero(®) against MenB disease. We used both cohort and transmission dynamic mathematical models, the latter allowing for herd effects, to consider the impact of vaccination on individuals aged 0-99 years. Vaccination strategies included infant and adolescent vaccination, alone or in combination, and with one-off catch-up programmes. German specific data were used where possible from routine surveillance data and the literature. We assessed the impact of vaccination through cases averted and quality adjusted life years (QALY) gained and calculated costs per QALY gained. Assuming 65% vaccine uptake and 82% strain coverage, infant vaccination was estimated to prevent 15% (34) of MenB cases over the lifetime of one birth cohort. Including herd effects from vaccination increased the cases averted by infant vaccination to 22%, with an estimated 8461 infants requiring vaccination to prevent one case. In the short term the greatest health benefit is achieved through routine infant vaccination with large-scale catch-up, which could reduce cases by 24.9% after 5 years and 27.9% after 10 years. In the long term (20+ years) policies including routine adolescent vaccination are most favourable if herd effects are assumed. Under base case assumptions with a vaccine list price of €96.96 the incremental cost-effectiveness ratio (ICER) was >€500,000 per QALY for all considered strategies. Given the current very low incidence of MenB disease in Germany, universal vaccination with Bexsero(®) would prevent only a small absolute number of cases, at a high overall cost.This work was supported by the Robert Koch Institute. HC’s work was supported by the National Institute for Health Research [RDA/03/07/014 and PDF-2012-05-245]. This work is produced by the authors under the terms of these research training fellowships issued by the NIHR. HC is a member of the NIHR Health Protection Research Unit in Evaluation of Interventions at University of Bristol. The views expressed in this publication are those of the authors and not necessarily those of the NHS, The National Institute for Health Research or the Department of Health. The NIHR had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.vaccine.2016.04.00

Pertussis-Impfquoten bei Erwachsenen in Deutschland

Hintergrund: Während in Deutschland seit 2001 eine Pertussis-Impfempfehlung für Risikogruppen besteht, wird erst seit 2009 von der Ständigen Impfkommission allen Erwachsenen die einmalige Pertussis-Impfung bei der nächsten fälligen Tetanus-Diphtherie-Auffrischimpfung empfohlen. Ziele dieser Studie waren: 1) Erhebung von Pertussis-Impfquoten bei Erwachsenen, 2) Abschätzung der Verwendungshäufigkeit tetanushaltiger Kombinationsimpfstoffe in Krankenhäusern. Methoden: Für 1) wurden Daten zweier bevölkerungsrepräsentativer Telefonsurveys unter Erwachsenen 2009/2010 analysiert (GEDA09: n = 21 262; GEDA10: n = 22 050). Einflussfaktoren des Pertussis-Impfstatus in Risikogruppen wurden mit logistischen Regressionsverfahren bestimmt. Für 2) wurde eine Befragung von 133 Krankenhausapotheken (betreuen 454 Krankenhäuser) für das Jahr 2007 durchgeführt. Ergebnisse: In GEDA10 hatten 5,9 % (95 %-Konfidenzintervall [KI] 5,5–6,3 %) der Befragten einen ausreichenden Pertussis-Impfschutz (Impfung in letzten 10 Jahren). Erwachsene, die einer Risikogruppe angehörten, hatten eine Impfquote von 10,7 % (95 %-KI 9,8–11,7 %). Mit höheren Pertussis-Impfquoten in Risikogruppen signifikant assoziiert waren u. a. Wohnort in den neuen Bundesländern und jüngeres Alter. Entgegen geltender Empfehlung wurden ca. 75 % der Tetanus-Impfungen in Notaufnahmen bzw. Stationen als monovalente Impfung verabreicht. Schlussfolgerungen: Angesichts hoher Pertussis-Inzidenzen und niedriger Durchimpfung in Risikogruppen und der Allgemeinbevölkerung ist die Steigerung der Pertussis-Impfquoten in Deutschland dringend geboten. Impfquotensteigernde Maßnahmen sollten unbedingt die impfende Ärzteschaft miteinbeziehen.Background: Pertussis vaccination for risk-groups (e. g. healthcare workers, employees of communal facilities, or persons with close contact to infants) has been recommended in Germany since 2001.  In 2009, single-dose acellular pertussis (ap) vaccination was recommended for all adults at the next tetanus-diphtheria (Td) booster. Study aims were to assess 1) pertussis vaccination coverage in adults, and 2) use of tetanus-containing combination vaccines in hospitals. Methods: For 1) we analysed data from two population-based telephone surveys conducted among adults in Germany in 2009/2010 (GEDA09: n = 21 262; GEDA10: n = 22 050). Factors associated with vaccination were identified by logistic regression analyses. For 2) a questionnaire survey of 133 hospital pharmacies serving 454 German hospitals was undertaken for the year 2007. Results: Overall, 5.9 % (95 % confidence interval [CI] 5.5–6.3 %) of GEDA10 participants reported up-to-date pertussis vaccination (ap-vaccination in past 10 years). In risk-groups, vaccination coverage was 10.7 % (95 %-CI 9.8–11.7 %). Residence in former East-Germany and younger age were independently associated with an adequate vaccination status. Contrary to prevailing recommendations, ~75 % of tetanus vaccines were administered as monovalent rather than Td- (or Tdap-)combination vaccines in hospitals. Conclusions: In light of high pertussis-incidence and low vaccination coverage in German adults, improvement of pertussis vaccine uptake is vital, e. g. through awareness campaigns targeting both physicians in private practice and hospitals