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We included 852 patients in a prospectively recruiting multicenter matched case-control study in Germany to assess vaccine effectiveness (VE) in preventing COVID-19-associated hospitalization (Delta-variant dominance). Two-dose VE was 89% (95%CI 84-93%) overall, 79% in patients with >2 comorbidities and 77% in adults aged 60-75 years. A third dose increased VE to >93% in all patient-subgroups.

National Immunization Technical Advisory Groups are groups of multi-disciplinary experts that provide scientific advice to policy makers to enable them to make informed immunization policy and programme decisions. NITAGs faced challenges using their routine approach to develop recommendations for COVID-19 vaccines during the pandemic. In response, the WHO Regional Office for Europe (Regional Office), with the support of the Robert Koch Institute, developed an innovative approach of a series of webinars, provision of materials, and remote technical assistance to address these challenges. Polls conducted during webinars were used to tailor future webinars and evaluate the effectiveness of these interventions. According to poll results, 76% of participants found the webinars and resources shared very useful in their work on COVID-19 vaccination. The Regional Office plans to build further upon the scope of online communication and establish a regional online platform for NITAGs to further support NITAGs and build capacity.

Background: Human Papillomavirus (HPV) vaccination of girls was introduced in Germany in 2007. However, data on the distribution of vaccine-relevant HPV types in the general population in Germany in the prevaccine era are limited. Methods: Serum samples collected during the German National Health Interview and Examination Survey 1998 (GNHIES98), a nationally representative study including men and women aged 18–79 years, were tested for antibodies to 19 mucosal and cutaneous HPV types. Multivariable regression models were developed to identify associations between demographic and behavioral characteristics and HPV seropositivity. Results: Of the 6517 serum samples tested, almost a quarter was seropositive for at least one of the nine HPV vaccine types with no clear age-pattern. HPV-6 and HPV-59 were the most common mucosal types, while HPV-1 and HPV-4 were the most common cutaneous HPV types. Factors independently associated with HPV-16 seroprevalence were seropositive to other sexually transmitted infections and lifetime number of sex partners, as well as urbanity (only among females). Conclusions: Prevalence of naturally acquired antibodies to HPV types which can be prevented by vaccination is high in both sexes and all age groups. These data can serve as baseline estimates to evaluate the population-level impact of the current vaccination strategy. Keywords: Human papillomavirus, Prevalence, Serology, Vaccine, General population, Seroepidemiologic studies, Predictors, Germany

Background: This umbrella review summarises the global evidence on the risk of severe COVID-19 outcomes in patients with pre-existing health conditions. Methods: Systematic reviews (SRs) were identified in PubMed, Embase/Medline, and seven pre-print servers until December 11, 2020. Risk estimates (odds ratio (OR), hazard ratio (HR), relative risk (RR)) for hospitalisation, intensive care unit admission, intubation, and death were extracted from primary studies. Meta-analyses were performed stratified by regions of the World Health Organisation. The evidence certainty was assessed using GRADE. Registration number CRD42020215846. Findings: 160 primary studies from 120 SRs contributed 464 estimates for 42 pre-existing conditions. Most studies were conducted in North America, European, and Western Pacific regions. Evidence from Africa, South/Latin America, and Eastern Mediterranean region was scarce. No evidence was available from South-East Asia region. Diabetes (HR 1∙2-2∙0 (1∙1-2∙8)), obesity (OR 1∙5-1∙75 (1∙1-2∙3)), heart failure (HR 1∙3-3∙3(0∙9-8∙2)), COPD (HR 1∙12-2∙2 (1∙1-3∙2)), and dementia (HR 1∙4-7.7 (1∙2-39∙6)) were associated with fatal COVID-19 in different regions, although the estimates varied. Evidence from Europe and North America showed that liver cirrhosis (OR 3∙2-5∙9 (0∙9-27∙7)) and active cancer (OR 1∙6-4∙7 (0∙5-14∙9)) were also associated with increased risk of death. Association between HIV and severe COVID-19 showed regional heterogeneity, with an increased risk of death in Africa (HR 1∙7 (1∙3-2∙2)). GRADE certainty was moderate to high for most associations. Interpretation: Risk of severe COVID-19 is consistently increased in certain patient subgroups across geographical regions, showing high variability in others. The results can be used to inform COVID-19 vaccine prioritisation or other intervention strategies. Funding Statement: Project ImVaCov – German Federal Ministry of Health Declaration of Interests: Authors declare no conflicts of interest.

Background The attitude towards vaccination is a major determinant of vaccination behavior; this also includes parents’ attitudes towards the immunization of their child. Negative attitudes have been associated with vaccine hesitancy and outbreaks of infectious diseases throughout the globe. This study aimed to assess how and why attitudes become more pro-vaccine or vaccine-skeptical over time, and which sources are especially influential in this process. Methods Prospective cohort study with measurements at time of recruitment during pregnancy and at +3, +6 and +14 months after childbirth with cross-sectional control groups. In total, 351 women entered the longitudinal analyses, while 204, 215 and 173 women were recruited in the cross-sectional control groups, respectively. Inclusion criteria were: (i) being at least 18 years of age, (ii) pregnant, (iii) primigravida, and (iv) living in Germany. Results During pregnancy mothers reported rather positive prior experiences with vaccinations. However, their judgment turned significantly more negative after the first vaccination experience with their child. Mixed-effects models showed that these changes were significantly related to increased risk perceptions and concerns about vaccination, which then had a negative impact on the vaccination attitude. In contrast, gaining more vaccine-related knowledge over time positively influenced attitude formation. Conclusions During the first year of their child’s life maternal attitudes towards vaccination are formed and guide future decisions whether to vaccinate or not vaccinate a child. Strategies should be implemented that improve mothers’ experiences when their newborn is vaccinated to prevent the development of vaccine hesitancy.

Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance systems accordingly. Targeted studies are needed, especially to better understand the effects of vaccinating seronegative individuals.

Many experts on vaccination are convinced that efforts should be made to encourage increased collaboration between National Immunization Technical Advisory Groups on immunization (NITAGs) worldwide. International meetings were held in Berlin, Germany, in 2010 and 2011, to discuss improvement of the methodologies for the development of evidence-based vaccination recommendations, recognizing the need for collaboration and/or sharing of resources in this effort. A third meeting was held in Paris, France, in December 2014, to consider the design of specific practical activities and an organizational structure to enable effective and sustained collaboration. The following conclusions were reached: (i) The proposed collaboration needs a core functional structure and the establishment or strengthening of an international network of NITAGs. (ii) Priority subjects for collaborative work are background information for recommendations, systematic reviews, mathematical models, health economic evaluations and establishment of common frameworks and methodologies for reviewing and grading the evidence. (iii) The programme of collaborative work should begin with participation of a limited number of NITAGs which already have a high level of expertise. The amount of joint work could be increased progressively through practical activities and pragmatic examples. Due to similar priorities and already existing structures, this should be organized at regional or subregional level. For example, in the European Union a project is funded by the European Centre for Disease Prevention and Control (ECDC) with the aim to set up a network for improving data, methodology and resource sharing and thereby supporting NITAGs. Such regional networking activities should be carried out in collaboration with the World Health Organization (WHO). (iv) A global steering committee should be set up to promote international exchange between regional networks and to increase the involvement of less experienced NITAGs. NITAGs already collaborate at the global level via the NITAG Resource Centre, a web-based platform developed by the Health Policy and Institutional Development Unit (WHO Collaborating Centre) of the Agence de Médecine Préventive (AMP-HPID). It would be appropriate to continue facilitating the coordination of this global network through the AMP-HPID NITAG Resource Centre. (v) While sharing work products and experiences, each NITAG would retain responsibility for its own decision-making and country-specific recommendations.

The Project on a Framework for Rating Evidence in Public Health (PRECEPT) is an international collaboration of public health institutes and universities which has been funded by the European Centre for Disease Prevention and Control (ECDC) since 2012. Main objective is to define a framework for evaluating and grading evidence in the field of public health, with particular focus on infectious disease prevention and control. As part of the peer review process, an international expert meeting was held on 13-14 June 2013 in Berlin. Participants were members of the PRECEPT team and selected experts from national public health institutes, World Health Organization (WHO), and academic institutions. The aim of the meeting was to discuss the draft framework and its application to two examples from infectious disease prevention and control. This article introduces the draft PRECEPT framework and reports on the meeting, its structure, most relevant discussions and major conclusions.

Background In Germany, 3-dose human papillomavirus (HPV) vaccination is recommended for 12–17 year-old females. Countrywide monitoring of HPV vaccination coverage (VC) does not exist, but small-scale surveys suggested suboptimal uptake. There is currently no concerted implementation strategy in place, and approaches for improved vaccine delivery are needed. Our objectives were to analyze health insurance claims data to estimate HPV VC in the target population and to assess the association of the routine adolescent health check-up ‘J1’ (offered to 12–14 year-olds) with HPV vaccine uptake. Methods We sampled a subset of 12–16 year-old females from claims data in 15 of the 16 German federal states. Sampling was based on documented physician contacts flanking the follow-up period 2008–2012. We reconstructed age- and region-stratified histories of individual-level HPV vaccination series and J1 utilization and calculated country-level estimates. Results The study sample represented 54% ( n = 1.04 million) of the total target population. VC estimates for starting (and completing) HPV vaccination series ranged from 6.1% (1.2%) among 12-year-olds to 47.6% (36.2%) among 16-year-olds. J1 utilization was 50% at maximum. In J1-attendees, 42.0% had received ≥1 vaccine doses, translating into a significant association of J1 utilization and vaccine uptake with a 6.9-fold higher likelihood in 12-year-olds and 1.4-fold higher likelihood in 16-year-olds of receiving HPV vaccination. Conclusion HPV VC in Germany is low. Adolescent check-up J1 is associated with increased and accelerated HPV vaccine uptake securing immunization before sexual debut and should be used as a tool to improve VC in the target population. However, J1 utilization is only moderate and more than half of attendees had not received HPV vaccination, which represents a substantial proportion of missed opportunities. This indicates that J1 needs both further promotion through legislative structures already in place for other health check-ups and more awareness as an opportunity to offer HPV vaccinations.

Rotavirus (RV) infection is the primary cause of severe gastroenteritis in children aged5 years in Germany and worldwide. In 2013 the German Standing Committee on Vaccination (STIKO) developed a national recommendation for routine RV-immunization of infants. To support informed decision-making we predicted the epidemiological impact of routine RV-vaccination in Germany using statistical modelling.We developed a population-based model for the dynamic transmission of RV-infection in a vaccination setting. Using data from the communicable disease reporting system and survey records on the vaccination coverage from the eastern federal states, where the vaccine was widely used before recommended at national level, we first estimated RV vaccine effectiveness (VE) within a Bayesian framework utilizing adaptive Markov Chain Monte Carlo inference. The calibrated model was then used to compute the predictive distribution of RV-incidence after achieving high vaccination coverage with the introduction of routine vaccination.Our model estimated that RV-vaccination provides high protection against symptomatic RV-infection (VE=96%; 95% credibility interval (CI): 91-99%) that remains at its maximum level for three years (95% CI: 1.43-5.80 years) and is fully waned after twelve years. At population level, routine vaccination at 90% coverage is predicted to reduce symptomatic RV-incidence among children aged5 years by 84% (95% prediction interval (PI): 71-90%) including a 2.5% decrease due to herd protection. Ten years after vaccine introduction an increase in RV incidences of 12% (95% PI: -16 to 85%) among persons aged 5-59 years and 14% (95% PI: -6 to 109%) within the age-group60 years was predicted.Routine infant RV-vaccination is predicted to considerably reduce RV-incidence in Germany among children5 years. Our work generated estimates of RV VE in the field and predicted the population-level impact, while adequately addressing the role of model and prediction uncertainty when making statements about the future.

There is a growing body of evidence on the risks and benefits of influenza vaccination in various target groups. Systematic reviews are of particular importance for policy decisions. However, their methodological quality can vary considerably.To investigate the methodological quality of systematic reviews on influenza vaccination (efficacy, effectiveness, safety) and to identify influencing factors.A systematic literature search on systematic reviews on influenza vaccination was performed, using MEDLINE, EMBASE and three additional databases (1990-2013). Review characteristics were extracted and the methodological quality of the reviews was evaluated using the assessment of multiple systematic reviews (AMSTAR) tool. U-test, Kruskal-Wallis test, chi-square test, and multivariable linear regression analysis were used to assess the influence of review characteristics on AMSTAR-score.Fourty-six systematic reviews fulfilled the inclusion criteria. Average methodological quality was high (median AMSTAR-score: 8), but variability was large (AMSTAR range: 0-11). Quality did not differ significantly according to vaccination target group. Cochrane reviews had higher methodological quality than non-Cochrane reviews (p=0.001). Detailed analysis showed that this was due to better study selection and data extraction, inclusion of unpublished studies, and better reporting of study characteristics (all p0.05). In the adjusted analysis, no other factor, including industry sponsorship or journal impact factor had an influence on AMSTAR score.Systematic reviews on influenza vaccination showed large differences regarding their methodological quality. Reviews conducted by the Cochrane collaboration were of higher quality than others. When using systematic reviews to guide the development of vaccination recommendations, the methodological quality of a review in addition to its content should be considered.

Summary Dengue is the second most common mosquito-borne disease affecting human beings. In 2009, WHO endorsed new guidelines that, for the first time, consider neurological manifestations in the clinical case classification for severe dengue. Dengue can manifest with a wide range of neurological features, which have been noted—depending on the clinical setting—in 0·5–21% of patients with dengue admitted to hospital. Furthermore, dengue was identified in 4–47% of admissions with encephalitis-like illness in endemic areas. Neurological complications can be categorised into dengue encephalopathy (eg, caused by hepatic failure or metabolic disorders), encephalitis (caused by direct virus invasion), neuromuscular complications (eg, Guillain-Barre syndrome or transient muscle dysfunctions), and neuro-ophthalmic involvement. However, overlap of these categories is possible. In endemic countries and after travel to these regions, dengue should be considered in patients presenting with fever and acute neurological manifestations.

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.

In November 2010, experts from European and North-American countries met in Berlin, Germany, to discuss improved methods for the development of evidence-based vaccination recommendations. The objectives of the workshop were to (i) review current procedures and experiences of National Immunization Technical Advisory Groups (NITAGs) in developing a framework for evidence-based vaccination recommendations, (ii) discuss the applicability of methods like Grading of Recommendations Assessment, Development and Evaluation (GRADE), and (iii) to identify opportunities for international collaboration to support NITAGs in the development of vaccination recommendations at country-level. Recognizing that a systematic and transparent approach is necessary to promote the quality and acceptance of vaccination recommendations, various decision making frameworks have been implemented by national and international advisory groups addressing common key aspects of knowledge, such as the burden of disease or characteristics of the vaccine. There are several challenges when grading the quality of evidence of some immunization-specific topics (e.g. population-level effects of vaccination). This does not, however, necessitate development of an entirely new systematic methodology. The participants concluded that (i) GRADE or a modification of this methodology is suitable for the grading of quality of evidence related to vaccine effectiveness and safety, and that (ii) international cooperation would be beneficial to develop common framework methodologies for certain aspects of national immunization recommendation developments in order to avoid duplication of efforts, to build on existing strengths, and to support NITAGs worldwide.

A dengue vaccine is likely to be available within the next 3-5 years and we estimated vaccine doses needed for dengue endemic countries (public and private markets) and non-endemic countries (travelers market) in the first 5 years after initial licensure. Calculations were based on 2015-2020 population projections for Asian and Americas endemic countries, and expected country-specific vaccination coverage in public, private, and travelers’ sectors. Fifty-four countries were considered dengue-endemic with a population of 2.8 billion, including an annual cohort of 54 million 12-23 month old children. During the 5-year period an estimated 645 million vaccine doses would be required for early childhood immunization and up to 2 billion doses for catch-up immunization, with 80% in endemic countries being in the public sector. An estimated 59-89 million doses would be needed for the travelers market. These should be considered upper-limit estimates, with actual demand dependent on country-specific introduction strategies, price and final vaccine product profile.

Data concerning the clinical and epidemiological features of travel-associated cryptosporidiosis are lacking. In order to investigate the impact of this disease on travellers' health, a retrospective study was conducted at the Institute of Tropical Medicine, Berlin. In total, 57 cryptosporidial infections were identified between 2000 and 2004, resulting in a prevalence of 2.9% in patients with travel-associated diarrhoea. Travel to south-central Asia, especially India, was associated with a higher prevalence of infection than was travel to other destinations. Clinically, the disease resembled giardiasis, but fever and arthralgias seemed to occur more frequently.

Failures of mefloquine prophylaxis in travellers returning from Africa have been reported repeatedly. Non-compliance to chemoprophylaxis is considered to be a major factor for failure. Only few reports on mefloquine prophylaxis failure in sub-Saharan Africa were able to report blood levels of the drug that were sufficient for prophylactic effectiveness. We report the case of a 44-year-old German female who travelled to Tanzania for 3 weeks. The patient reported that she never missed a dose of mefloquine during her weekly prophylaxis schedule. Four weeks after returning from Tanzania, the patient presented with fever, headache and myalgia. Only a few trophozoites of Plasmodium falciparum were found in a thick film. Blood levels of mefloquine at that stage were at 1400 ng/ml, thus largely excluding non-compliance and malabsorption. To our knowledge, this is the first case of confirmed prophylaxis failure due to mefloquine resistance in East Africa.