[Important vector-borne infectious diseases among humans in Germany. Epidemiological aspects]. / Wichtige, durch Vektoren übertragene Infektionskrankheiten beim Menschen in Deutschland. Epidemiologische Aspekte.

Vector-borne infections pathogenic to humans play an important role in Germany. The relevant zoonotic pathogens are either endemic throughout Germany (e.g. Borrelia burgdorferi sensu latu) or only in specific regions, e.g. tick-borne encephalitis (TBE) virus and hantavirus. They cause a substantial burden of disease. Prevention and control largely rely on public advice and the application of personal protective measures (e.g. TBE virus vaccination and protection against vectors). High quality surveillance and targeted epidemiological studies are fundamental for the evaluation of temporal and spatial risks of infection and the effectiveness of preventive measures. Aside from endemic pathogens, vector-borne infections acquired abroad, mostly transmitted by mosquitoes, have to be systematically and intensively monitored as well, to assess the risk of infection for German residents traveling abroad and to adequately evaluate the risk of autochthonous transmission. Related issues, such as invasive species of mosquitoes in Germany and climate change, have to be taken into consideration. Such pathogens include West Nile, dengue and chikungunya viruses, as well as malaria parasites (Plasmodium species). The article presents an overview of the epidemiological situation of selected relevant vector-borne infections in Germany.

Time since last vaccine dose in PCR-positive and PCR-negative children with suspected pertussis to monitor pertussis vaccine effectiveness.

We evaluated whether the results of diagnostic polymerase chain reaction (PCR) testing combined with time since last vaccine dose could be used to monitor the effectiveness of acellular pertussis vaccines. In 258 consecutive nasopharyngeal swabs from children and adolescents with typical pertussis symptoms, 80 were positive and 178 were negative in PCR for Bordetella pertussis DNA (IS 481). Time since last vaccine dose was available for 152 patients, of which 120 were fully immunised. Among the fully vaccinated patients, the median age of 41 PCR-positive patients was 8.4 years (range 0.9-12.3) and that of 79 PCR-negative cases was 3.3 years (range 0.4-14.1) (p < 0.01). The median time since last pertussis vaccine dose was 6.05 years [95 % confidence interval (CI): 0.5-10.9] in PCR-positive cases and 2.22 years (95 % CI: 0.04-9.23) in PCR-negative cases (p < 0.001). The use of diagnostic PCR results from pertussis cases together with time since last vaccine dose permits estimates of the duration of protection after vaccination with acellular pertussis vaccines that are in keeping with more complex studies.

[Pertussis vaccination coverage among adults in Germany]. / Pertussis-impfquoten bei erwachsenen in Deutschland.

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.

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.

Virus detection in questing ticks is not a sensitive indicator for risk assessment of tick-borne encephalitis in humans.

Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted arbovirus causing human disease in Europe, but information on its endemic occurrence varies between countries because of differences in surveillance systems. Objective data are necessary to ascertain the disease risk for vaccination recommendations and other public health interventions. In two independent, separately planned projects, we used real-time RT-PCR to detect TBE virus in questing ticks. In Poland, 32 sampling sites were selected in 10 administrative districts located in regions where sporadic TBE cases were reported. In Germany, 18 sampling sites were selected in two districts located in a region with high TBE incidence. Altogether, >16,000 ticks were tested by real-time RT-PCR, with no sample testing positive for TBEV. A systematic search for published studies on TBEV prevalence in ticks in Poland and Germany also suggested that testing large numbers of collected ticks could not consistently assure virus detection in known endemic foci. Although assignment of results to administrative regions is essential for TBE risk mapping, this was possible in only 10 (investigating 22,417 ticks) of 15 published studies (>50,000 ticks) identified. We conclude that the collection and screening of ticks by real-time RT-PCR cannot be recommended for assessment of human TBE risk. Alternative methods of environmental TBEV monitoring should be considered, such as serological monitoring of rodents or other wildlife.

Comparative hepatitis A seroepidemiology in 10 European countries.

The WHO recommends hepatitis A virus (HAV) immunization according to level of transmission and disease burden. We aimed to identify susceptible age groups by standardized serosurveys to inform HAV vaccination policy in participating countries: Belgium, Czech Republic, England, Finland, Germany, Italy, Lithuania, Malta, Romania, and Slovakia. Each country tested national serum banks (n = 1854-6748), collected during 1996-2004, for anti-HAV antibodies. Local laboratory results were standardized to common units. Forty-one per cent of those aged <30 years and 6% of those aged ≥30 years were susceptible to HAV in Romania; compared to 70-94% and 26-71%, respectively, elsewhere. Romania reported high HAV incidence in children and young adults. Other countries reported HAV disease primarily in older risk groups. The results suggest low level of HAV transmission in most of Europe. Romania, however, appeared as an area with intermediate transmission. Vaccination of risk groups in countries with high susceptibility of young and middle-aged adults needs to be continued.

[Infections with pneumococci, menigococci, H. influenzae and diphtheria in Germany: the RKI Reference Network for Invasive Bacterial Infections (IBI) at the 5th Würzburg Workshop on Epidemiology, Prevention and Therapy for Invasive Meningococcal Diseases 2010 (meeting report)]. / Infektionen mit Pneumokokken, Meningokokken, H. influenzae und Diphtherie in Deutschland: das RKI Referenznetzwerk für Invasive Bakterielle Infektionen (IBI) beim 5. Würzburger Workshop zur Epidemiologie, Prävention und Therapie von invasiven Meningokokkenerkrankung 2010 (Tagungsbericht).

The surveillance and prevention of invasive bacterial infections requires flexible strategic coordination of all involved health-care professionals. For this purpose, the German National Reference Centres for Meningococci, Streptococci and the Consultant Laboratories for Haemophilus influenzae and diphtheria have formed the Reference Network for Invasive bacterial infections (IBI). The 5th Würzburg Workshop on Meningococcal Diseases 2010 provided the network with a forum for the interdisciplinary exchange between scientists, public health professionals, medical microbiologists and clinicians. The topics covered the analysis of surveillance data for meningococcal disease in the last decade, as well as methods to control for antibody response following vaccination, including a serum bactericidal antibody (SBA) assay, and the development of new vaccines that also include the most common serogroup B. The presentation on diphtheria showed that this rare disease in Germany has become a diagnostic challenge, and that apart from the classical pathogen also toxigenic C. ulcerans strains must be considered. Due to the successful vaccination against Hib, H. influenzae disease has changed from a classical childhood disease to an infection of elderly people mainly caused by unencapsulated strains. Following the introduction of vaccines, changes in the serotype distribution and antibiotic resistance profiles have become apparent for S. pneumoniae infections. The epidemiological data were complemented by clinical aspects concerning the vaccination of immunocompromised children.

What is the evidence for giving chemoprophylaxis to children or students attending the same preschool, school or college as a case of meningococcal disease?

We performed a systematic literature review to assess the effectiveness of chemoprophylaxis for contacts of sporadic cases of invasive meningococcal disease (IMD) in educational settings. No studies directly compared IMD risk in contacts with/without chemoprophylaxis. However, compared to the background incidence, an elevated IMD risk was identified in settings without a general recommendation for chemoprophylaxis in pre-schools [pooled risk difference (RD) 58·2/105, 95% confidence interval (CI) 27·3-89·0] and primary schools (pooled RD 4·9/105, 95% CI 2·9-6·9) in the ~30 days after contact with a sporadic IMD case, but not in other educational settings. Thus, limited but consistent evidence suggests the risk of IMD in pre-school contacts of sporadic IMD cases is significantly increased above the background risk, but lower than in household contacts (pooled RD for household contacts with no chemoprophylaxis vs. background incidence: 480·1/105, 95% CI 321·5-639·9). We recommend chemoprophylaxis for pre-school contacts depending on an assessment of duration and closeness of contact.

Enhanced surveillance during a large outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/verotoxin-producing Escherichia coli in Germany, May to June 2011.

Germany has a well established broad statutory surveillance system for infectious diseases. In the context of the current outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/ verotoxin-producing Escherichia coli in Germany it became clear that the provisions of the routine surveillance system were not sufficient for an adequate response. This article describes the timeline and concepts of the enhanced surveillance implemented during this public health emergency.

Pandemic influenza A(H1N1) 2009 breakthrough infections and estimates of vaccine effectiveness in Germany 2009-2010.

During the 2009 influenza pandemic, a monovalent AS03-adjuvanted vaccine was almost exclusively used in Germany for immunisation against the 2009 pandemic influenza A(H1N1) virus. One-dose vaccination was recommended for all age groups. We applied the screening method for the rapid assessment of vaccine effectiveness (VE) based on reported data of vaccinated and unvaccinated pandemic influenza cases and vaccination coverage estimates. Preliminary results demonstrate excellent VE in persons aged 14-59 years (96.8%; 95% confidence interval (CI): 95.2-97.9) and moderately high VE in those 60 years or older (83.3%; 95% CI: 71.0-90.5).

Changes to the varicella and pertussis immunisation schedule in Germany 2009: background, rationale and implementation.

In July 2009, the German Standing Committee on Vaccination (STIKO) modified its recommendations for varicella and pertussis vaccination, based on newly available data on disease epidemiology, vaccine effectiveness (VE) and safety, and an evaluation of the feasibility of the recommended immunisation strategy. The recommendation for varicella vaccine now includes a routine two-dose schedule with the administration of the first dose at the age of 11 to 14 months and the second dose at the age of 15 to 23 months, with a minimum interval of four weeks between these doses. Furthermore, STIKO recommended adding a one-time pertussis booster to the adult vaccination schedule to expand the cocoon strategy in place since 2004. The recommendation of a booster vaccination with an acellular pertussis vaccine every 10 years for persons employed in the care of pre-school children and for healthcare personnel in paediatric, gynaecologic and obstetric health facilities was extended to persons employed in schools and in other institutions caring for older children, and to all healthcare personnel. These recommendations were based on available epidemiological data showing an increase in incidence from 7-10 cases per 100,000 inhabitants in 2002-2004 to over 30 by 2007. Moreover, the high burden of pertussis in infants at 94 hospitalised cases per 100,000 infants in 2007 suggested that the previous cocoon strategy was insufficient.

Low hepatitis B immunogenicity of a hexavalent vaccine widely used in Germany: results of the German Health Survey for Children and Adolescents, 2003-2006.

The success of childhood vaccination against hepatitis B relies on persistence of immunity into adolescence and adulthood. In 2000, two hexavalent vaccines with a hepatitis B component (Hexavac, Infanrix hexa) were introduced in Germany. Hexavac was withdrawn in 2005 amidst concerns about its long-term hepatitis B protection. We compared hepatitis B surface antibody (anti-HBs) levels in children fully vaccinated with Hexavac or Infanrix hexa (n=477) in a secondary data analysis of a large cross-sectional health survey in Germany. On average 2.4 years after vaccination, 25.3% of Hexavac vaccinees had anti-HBs levels <10 mIU/ml (95% CI 19.0-32.8) compared to 4.7% of Infanrix hexa vaccinees (95% CI 2.4-8.9). These findings suggest that short-term hepatitis B immunogenicity in Hexavac vaccinees may also be weaker. Further studies are warranted to assess whether Hexavac vaccinees should be re-vaccinated or receive a booster vaccination before these birth cohorts reach adolescence.

Risk of transmitting meningococcal infection by transient contact on aircraft and other transport.

Contact tracing of persons with meningococcal disease who have travelled on aeroplane or other multi-passenger transport is not consistent between countries. We searched the literature for clusters of meningococcal disease linked by transient contact on the same plane, train, bus or boat. We found reports of two clusters in children on the same school bus and one in passengers on the same plane. Cases within each of these three clusters were due to strains that were genetically indistinguishable. In the aeroplane cluster the only link between the two cases was through a single travel episode. The onset of illness (2 and 5 days after the flight) is consistent with infection from an unidentified carrier around the time of air travel. In contrast to the established risk of transmission from a case of tuberculosis, it is likely that the risk from a case of meningococcal disease to someone who is not identified as a close contact is exceedingly low. This should be considered in making international recommendations for passenger contact tracing after a case of meningococcal disease on a plane or other multi-passenger transport.

A comparison of hepatitis B seroepidemiology in ten European countries.

To inform current and future vaccination strategies, we describe the seroepidemiology of hepatitis B virus (HBV) infection in ten representative European countries using standardized serology that allowed international comparisons. Between 1996 and 2003, national serum banks were compiled by collecting residual sera or by community sampling; sera were then tested by each country using its preferred enzyme immunoassays and testing algorithm, and assay results were standardized. Information on current and past HBV vaccination programmes in each country was also collected. Of the ten countries, six reported low levels (<3%) of antibodies against HBV core antigen (anti-HBc). Of the eight countries testing for HBV surface antigen (HBsAg), the highest prevalence was reported in Romania (5.6%) and in the remaining seven countries prevalence was <1%. Universal HBV vaccination programmes had been established in seven countries as recommended by the World Health Organization, but the seroprevalence of antibodies against HBsAg (anti-HBs) was lower than the reported vaccine coverage in three countries. Regular serological surveys to ascertain HBV status within a population, such as reported here, provide important data to assess the need for and to evaluate universal HBV vaccination programmes.

Invasive meningococcal disease with fatal outcome in a Swiss student visiting Berlin.

Following the fatal invasive meningococcal disease in a Swiss student who had been visiting Berlin, several public health institutions on local, regional and national level cooperated to ensure that the appropriate measures such as contact tracing and post exposure prophylaxis were taken to prevent further cases. The incidence highlighted the importance of early disease notification and showed that if an infectious disease requiring public health action occurs in an international context, it is vital that relevant information is communicated to all levels of the public health systems of the countries involved.

Effectiveness of vaccinating household contacts in addition to chemoprophylaxis after a case of meningococcal disease: a systematic review.

SUMMARYWe performed a systematic review to estimate the effectiveness of vaccination, in addition to chemoprophylaxis, in preventing meningococcal disease among household contacts. Medline, EMBASE, EMGM, and EUIBIS were used for data collection. Studies reporting on at least 100 primary cases and on subsequent cases in household settings with follow-up of more than 2 weeks after onset of disease in the primary case were reviewed. A meta-analysis was used to calculate the average attack rate in household contacts given chemoprophylaxis 14-365 days after onset of disease in the primary case. In total, 652 studies were identified, five studies and one unpublished report met the inclusion criteria. The weighted average attack rate was 1.1/1000 household contacts (95% CI 0.7-1.7). This review supports vaccination of household contacts in addition to chemoprophylaxis to reduce the risk of meningococcal disease among household contacts of a case caused by a vaccine-preventable serogroup.

[3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease in Würzburg 2006]. / 3. Würzburger Workshop zur Epidemiologie, Prävention und Therapie der invasiven Meningokokkenerkrankung 2006.

On October 5th, 2006, the German Reference Centre for Meningococci (NRZM) held the 3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease, in collaboration with the German Society for Hygiene and Microbiology (DGHM). Given the recent recommendation of the German Standing Committee on Vaccination (STIKO) for conjugate meningococcal C vaccination of all children in the second year of life, observations from meningococcal C conjugate vaccination campaigns in other European countries were presented and compared to the German situation. Moreover, the newly implemented cluster detection routines employed at the NRZM and their integration into the interactive geographical information system EpiScanGIS were shown. Based on recent experiences from regional outbreaks in Oberallgäu, Sangerhausen, and Greater Aachen, examples for public health intervention were given at the conference. In addition, current developments in the area of meningococcal research, as well as trends in antimicrobial susceptibility were covered. Finally, the latest evidence concerning the clinical management and chemoprophylaxis of this invasive bacterial disease was discussed.

Capture-recapture analysis to estimate the incidence of invasive meningococcal disease in Germany, 2003.

The incidence of invasive meningococcal disease (IMD) in Germany in 2003 was estimated by the two-source capture-recapture method. As a unique personal identifier was unavailable, cases with IMD tested at the National Reference Centre for Meningococci (NRZM) were matched with cases reported to the Robert Koch Institute (RKI) through the statutory surveillance system by using demographic and disease-specific variables common to both datasets. The estimated overall incidence was 1.1 IMD cases/100,000 inhabitants, with a sensitivity of ascertainment of 64.8% for NRZM and 89.4% for RKI. Case-fatality rate was estimated at 8.8%. Adjustment for heterogeneity of capture according to age, region and serogroup observed in the NRZM (but not RKI) source had minimal effect on the estimated incidence. The IMD incidence estimated by capture-recapture analysis is thus only slightly higher than through statutory surveillance data. As a degree of positive dependence between the systems cannot be ruled out, this estimate may still be an underestimate. However, under ascertainment appears insufficient to explain the low incidence of IMD in Germany compared to other European countries.