ADVANCE system testing: Can coverage of pertussis vaccination be estimated in European countries using electronic healthcare databases: An example.

INTRODUCTION: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines, using existing healthcare databases in Europe. The objective of this paper was to assess the feasibility of using electronic healthcare databases to estimate dose-specific acellular pertussis (aP) and whole cell pertussis (wP) vaccine coverage. METHODS: Seven electronic healthcare databases in four European countries (Denmark (n = 2), UK (n = 2), Spain (n = 2) and Italy (n = 1)) participated in this study. Children were included from birth and followed up to age six years. Vaccination exposure was obtained from the databases and classified by type (aP or wP), and dose 1, 2 or 3. Coverage was estimated using period prevalence. For the 2006 birth cohort, two estimation methods for pertussis vaccine coverage, period prevalence and cumulative incidence were compared for each database. RESULTS: The majority of the 2,575,576 children included had been vaccinated at the country-specific recommended ages. Overall, the estimated dose 3 coverage was 88-97% in Denmark (birth cohorts from 2003 to 2014), 96-100% in the UK (2003-2014), 95-98% in Spain (2004-2014) and 94% in Italy (2006-2007). The estimated dose 3 coverage per birth cohort in Denmark and the UK differed by 1-6% compared with national estimates, with our estimates mostly higher. The estimated dose 3 coverage in Spain differed by 0-2% with no consistent over- or underestimation. In Italy, the estimates were 3% lower compared with the national estimates. Except for Italy, for which the two coverage estimation methods generated the same results, the estimated cumulative incidence coverages were consistently 1-10% lower than period prevalence estimates. CONCLUSION: This study showed that it was possible to provide consistent estimates of pertussis immunisation coverage from the electronic healthcare databases included, and that the estimates were comparable with the national estimates.

Lessons from an online vaccine communication project.

Most members of the general public use the internet to research health topics. However, the quality of vaccine-related material available online is mixed and internet search engines often bring web users to low-quality anti-vaccine websites. We present a case study of a pro-vaccine information hub launched in 2011. Vaccines Today provides high-quality information about vaccines and diseases, expert interviews, answers to frequently asked questions, parent/patient stories and videos/infographics. Twitter, Facebook, YouTube and Instagram are used to share this content and to engage with various online audiences. This Commentary outlines what works in online communication about vaccines and offers proposals for improving the impact of online vaccine advocacy. The value of networking to boost visibility and search engine ranking is emphasised. Furthermore, we present the case for the sharing and application of best practice in online communication.

The ADVANCE Code of Conduct for collaborative vaccine studies.

Lessons learnt from the 2009 (H1N1) flu pandemic highlighted factors limiting the capacity to collect European data on vaccine exposure, safety and effectiveness, including lack of rapid access to available data sources or expertise, difficulties to establish efficient interactions between multiple parties, lack of confidence between private and public sectors, concerns about possible or actual conflicts of interest (or perceptions thereof) and inadequate funding mechanisms. The Innovative Medicines Initiative's Accelerated Development of VAccine benefit-risk Collaboration in Europe (ADVANCE) consortium was established to create an efficient and sustainable infrastructure for rapid and integrated monitoring of post-approval benefit-risk of vaccines, including a code of conduct and governance principles for collaborative studies. The development of the code of conduct was guided by three core and common values (best science, strengthening public health, transparency) and a review of existing guidance and relevant published articles. The ADVANCE Code of Conduct includes 45 recommendations in 10 topics (Scientific integrity, Scientific independence, Transparency, Conflicts of interest, Study protocol, Study report, Publication, Subject privacy, Sharing of study data, Research contract). Each topic includes a definition, a set of recommendations and a list of additional reading. The concept of the study team is introduced as a key component of the ADVANCE Code of Conduct with a core set of roles and responsibilities. It is hoped that adoption of the ADVANCE Code of Conduct by all partners involved in a study will facilitate and speed-up its initiation, design, conduct and reporting. Adoption of the ADVANCE Code of Conduct should be stated in the study protocol, study report and publications and journal editors are encouraged to use it as an indication that good principles of public health, science and transparency were followed throughout the study.

Vaccine hesitancy and healthcare providers.

While most people vaccinate according to the recommended schedule, this success is challenged by individuals and groups who delay or refuse vaccines. The aim of this article is to review studies on vaccine hesitancy among healthcare providers (HCPs), and the influences of their own vaccine confidence and vaccination behaviour on their vaccination recommendations to others. The search strategy was developed in Medline and then adapted across several multidisciplinary mainstream databases including Embase Classic & Embase, and PschInfo. All foreign language articles were included if the abstract was available in English. A total of 185 articles were included in the literature review. 66% studied the vaccine hesitancy among HCPs, 17% analysed concerns, attitudes and/or behaviour of HCPs towards vaccinating others, and 9% were about evaluating intervention(s). Overall, knowledge about particular vaccines, their efficacy and safety, helped to build HCPs own confidence in vaccines and their willingness to recommend vaccines to others. The importance of societal endorsement and support from colleagues was also reported. In the face of emerging vaccine hesitancy, HCPs still remain the most trusted advisor and influencer of vaccination decisions. The capacity and confidence of HCPs, though, are stretched as they are faced with time constraints, increased workload and limited resources, and often have inadequate information or training support to address parents' questions. Overall, HCPs need more support to manage the quickly evolving vaccine environment as well as changing public, especially those who are reluctant or refuse vaccination. Some recommended strategies included strengthening trust between HCPs, health authorities and policymakers, through more shared involvement in the establishment of vaccine recommendations.

Is It Time for Vaccination to "Go Viral"?

To promote and sustain excellent vaccination coverage, while preserving the key core values of ethics, truth, transparency and trust, the vaccine community should adopt modern digital communication strategies. This article summarizes our views-as experts in multidisciplinary field of vaccinology (consisting of an anthropologist, a public health policy advisor, a vaccine industry expert, a health care journalist and a practicing physician)-which were presented at a satellite symposium held at the 33rd European Society of Paediatric Infectious Disease conference in Leipzig, Germany, in May 2015. This article aims to suggest and recommend strategies to promote vaccination awareness, and highlight proactive measures for building, maintaining and enhancing trust in vaccination through innovative communication and evidence-based interaction with the end user. We believe that converting the results of vaccine research into a successful vaccination program, and replacing misinformation with evidence-based communication, will require a multidisciplinary approach that embraces modern digital and tailored applications to reach out to all populations.

Sustaining Vaccine Confidence in the 21st Century.

Vaccination provides many health and economic benefits to individuals and society, and public support for immunization programs is generally high. However, the benefits of vaccines are often not fully valued when public discussions on vaccine safety, quality or efficacy arise, and the spread of misinformation via the internet and other media has the potential to undermine immunization programs. Factors associated with improved public confidence in vaccines include evidence-based decision-making procedures and recommendations, controlled processes for licensing and monitoring vaccine safety and effectiveness and disease surveillance. Community engagement with appropriate communication approaches for each audience is a key factor in building trust in vaccines. Vaccine safety/quality issues should be handled rapidly and transparently by informing and involving those most affected and those concerned with public health in effective ways. Openness and transparency in the exchange of information between industry and other stakeholders is also important. To maximize the safety of vaccines, and thus sustain trust in vaccines, partnerships are needed between public health sector stakeholders. Vaccine confidence can be improved through collaborations that ensure high vaccine uptake rates and that inform the public and other stakeholders of the benefits of vaccines and how vaccine safety is constantly assessed, assured and communicated.

Impact of pneumococcal vaccination in Denmark during the first 3 years after PCV introduction in the childhood immunization programme.

BACKGROUND AND AIMS: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Denmark in October 2007 in a 2+1 schedule with a catch-up programme for children up to 17 months of age. To assess the impact of PCV we evaluated on the whole population: (1) direct and indirect effects on incidence of invasive pneumococcal disease (IPD), (2) changes in pneumococcal serotype distribution and (3) IPD related mortality. METHODS: We compared disease incidence in pre-PCV (years 2000-2007) and PCV periods (years 2008-2010) based on national surveillance data. RESULTS: In children aged 0-5 years the overall incidence of IPD decreased from 26.7 to 16.3 cases per 100,000 (IRR 0.58; 95% Confidence Interval (CI) [0.48-0.69]) and case fatality declined from 1.8% (12 deaths) in the eight-year pre-PCV period to 0% (no deaths) in the three-year PCV period. In the whole population the overall incidence of IPD and of IPD caused by vaccine serotypes declined significantly from 19.5 to 17.7 and from 7.7 to 3.8 cases per 100,000 persons comparing the two periods. The incidence of IPD due to non-vaccine serotypes (NVT-IPD) increased significantly from 11.8 to 13.9 cases per 100,000 in the whole population (incidence rate ratio 1.18; 95% CI [1.12-1.24]) with predominance of the serotypes 1.7F and 19A. CONCLUSIONS: We report a marked decline in incidence in IPD in both vaccinated and non-vaccinated age groups and a minor but statistically significant increase in incidence of IPD due to NVTs in both vaccinated and non-vaccinated groups with predominance of serotypes covered by higher valence pneumococcal conjugate vaccines.

Influenza-associated illness is an important contributor to febrile convulsions in Danish children.

OBJECTIVE: To determine the burden of febrile convulsions attributed to influenza like illness in a western country during ten influenza seasons. METHODS: Based on national Danish registries, we explored the association between influenza like illness (ILI) activity and weekly number of hospital admittances for febrile convulsions in time-series analyses. We included data on 59,870 admissions for febrile convulsions in children between three months and five years of age in the period 1995-2005. RESULTS: There was a significant relation between ILI-activity and number of children admitted for febrile convulsions with a systematic increase in admissions to pediatric wards about one week before the national surveillance system detected the corresponding rise in ILI-activity. The yearly number of admissions attributable to ILI varied from 11 to 47% of admissions and was highest during influenza epidemics. This was in particular observed in seasons when a new strain of influenza A/H3N2 was circulating. During these epidemics, influenza contributed to 29-47% of admissions. CONCLUSIONS: Influenza like illness is associated with a considerable burden of febrile convulsions in children, most pronounced in years with epidemics. As febrile convulsions are just one of many complications contributing to the burden of influenza in children, this should be taken into consideration when planning a vaccination strategy for preventing influenza-related morbidity in younger children.

Toward rubella elimination in Europe: an epidemiological assessment.

BACKGROUND: The elimination of rubella and prevention of congenital rubella syndrome (CRS) by 2015 are established goals for Europe. Our aim was to review the epidemiology of rubella in relation to this goal. MATERIAL AND METHODS: National surveillance institutions from 32 European countries provided information on rubella and CRS surveillance systems and data for 2000-08. We reported the number of notified rubella cases by year for countries with a national mandatory notification system for rubella covering total country population consistently throughout 2000-08 and analysed rubella surveillance data for 2008. RESULTS: Throughout 2000-08, 24 countries conducted passive routine surveillance based on mandatory reporting rubella covering total country population. Altogether these countries reported 526,751 rubella cases. The median incidence per million inhabitants declined from 7.2 in 2000 to 0.3 in 2008. By 2008, the number of countries with mandatory notification systems for rubella increased to 28. These countries reported 21,475 rubella cases of which 1.5% (n=317) were laboratory-confirmed. Most cases (n=21,075; 98%) were reported from Poland, Italy and Romania. Ten countries reported zero rubella cases and five others reported an incidence of <1 per million inhabitants. In 2008, 20 CRS cases were reported from five countries. CONCLUSION: The overall decline in rubella incidence and increase in the number of countries conducting rubella surveillance through a mandatory notification system are notable achievements toward the goal of rubella elimination in Europe. However, in a few countries with high rubella incidence the risk for CRS still exists. Achievement and maintenance of the required high vaccination coverage and high-quality surveillance of rubella and CRS including laboratory testing of all suspected cases are fundamental to eliminate rubella and prevent CRS in Europe.

Excess mortality related to seasonal influenza and extreme temperatures in Denmark, 1994-2010.

BACKGROUND: In temperate zones, all-cause mortality exhibits a marked seasonality, and one of the main causes of winter excess mortality is influenza. There is a tradition of using statistical models based on mortality from respiratory illnesses (Pneumonia and Influenza: PI) or all-cause mortality for estimating the number of deaths related to influenza. Different authors have applied different estimation methodologies. We estimated mortality related to influenza and periods with extreme temperatures in Denmark over the seasons 1994/95 to 2009/10. METHODS: We applied a multivariable time-series model with all-cause mortality as outcome, activity of influenza-like illness (ILI) and excess temperatures as explanatory variables, controlling for trend, season, age, and gender. Two estimates of excess mortality related to influenza were obtained: (1) ILI-attributable mortality modelled directly on ILI-activity, and (2) influenza-associated mortality based on an influenza-index, designed to mimic the influenza transmission. RESULTS: The median ILI-attributable mortality per 100,000 population was 35 (range 6 to 100) per season which corresponds to findings from comparable countries. Overall, 88% of these deaths occurred among persons ≥ 65 years of age. The median influenza-associated mortality per 100,000 population was 26 (range 0 to 73), slightly higher than estimates based on pneumonia and influenza cause-specific mortality as estimated from other countries. Further, there was a tendency of declining mortality over the years. The influenza A(H3N2) seasons of 1995/96 and 1998/99 stood out with a high mortality, whereas the A(H3N2) 2005/6 season and the 2009 A(H1N1) influenza pandemic had none or only modest impact on mortality. Variations in mortality were also related to extreme temperatures: cold winters periods and hot summers periods were associated with excess mortality. CONCLUSION: It is doable to model influenza-related mortality based on data on all-cause mortality and ILI, data that are easily obtainable in many countries and less subject to bias and subjective interpretation than cause-of-death data. Further work is needed to understand the variations in mortality observed across seasons and in particular the impact of vaccination against influenza.

Burden of illness of the 2009 pandemic of influenza A (H1N1) in Denmark.

We analysed Danish surveillance data to estimate influenza-associated morbidity and mortality in 2009. To obtain population-based estimates of the clinical attack rate, we combined data from two different primary health care surveillance systems, national numbers of the proportion of positive influenza tests, and data from a web-based interview on health care seeking behaviour during the pandemic. From a national registry, we obtained data on hospital admissions (ICD-10 codes) for influenza related conditions. Admission to intensive care was monitored by a dedicated surveillance scheme. Mortality was estimated among laboratory confirmed cases but was also expressed as excess all-cause mortality attributed to influenza-like illness in a multivariable time series analysis. In total, we estimated that 274,000 individuals (5%) in Denmark experienced clinical illness. The highest attack rate was found in children 5-14 years (15%). Compared with the expected number of hospital admissions, there was an 80% increase in number of influenza related hospital admissions in this age group. The numbers of patients admitted to intensive care approached 5% of the national capacity. Estimates of the number of deaths ranged from 30 to 312 (0.5-5.7 per 100,000 population) depending on the methodology. In conclusion, the pandemic was characterised by high morbidity and unprecedented high rates of admissions to hospitals for a range of influenza-related conditions affecting mainly children. Nonetheless, the burden of illness was lower than assumed in planning scenarios, and the present pandemic compares favourable with the 20th century pandemics.

[Infectious diseases and climate change]. / Smitsomme sygdomme og klimaforandringer.

Climate changes will likely have an impact on the spectrum of infectious diseases in Europe. We may see an increase in vector-borne diseases, diseases spread by rodents such as Hantavirus, and food- and water-borne diseases. As the effects of climate changes are likely to occur gradually, a modern industrialised country such as Denmark will have the opportunity to adapt to the expected changes.

Measles in Europe: an epidemiological assessment.

BACKGROUND: Measles persists in Europe despite the incorporation of the measles vaccine into routine childhood vaccination programmes more than 20 years ago. Our aim was therefore to review the epidemiology of measles in relation to the goal of elimination by 2010. METHODS: National surveillance institutions from 32 European countries submitted data for 2006-07. Data for age-group, diagnosis confirmation, vaccination, hospital treatment, the presence of acute encephalitis as a complication of disease, and death were obtained. 30 countries also supplied data about importation of disease. Clinical, laboratory-confirmed, and epidemiologically linked cases that met the requirements for national surveillance were analysed. Cases were separated by age: younger than 1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years, and older than 20 years. Countries with indigenous measles incidence per 100 000 inhabitants per year of 0, less than 0.1, 0.1-1, and more than 1 were grouped into categories of zero, low, moderate, and high incidence, respectively. FINDINGS: For the 2 years of the study, 12 132 cases of measles were recorded with most cases (n=10 329; 85%) from five countries: Romania, Germany, UK, Switzerland, and Italy. Most cases were unvaccinated or incompletely vaccinated children; however, almost a fifth were aged 20 years or older. For the same 2 years, seven measles-related deaths were recorded. High measles incidence in some European countries revealed suboptimum vaccination coverage. Of the 210 cases that were reported as being imported, 117 (56%) came from another country within Europe and 43 (20%) from Asia. INTERPRETATION: The suboptimum vaccination coverage raises serious doubts that the goal of elimination by 2010 can be attained. Achievement and maintenance of optimum vaccination coverage and improved surveillance are the cornerstones of the measles elimination plan for Europe.

The benefit of molecular characterization during a measles upsurge in Denmark.

Molecular characterization of measles virus was part of the epidemiological investigation of 27 measles cases reported in Denmark in 2006. RT-PCR detected measles virus RNA from various types of clinical specimens in 24 cases. Virus genotypes were determined by sequencing the nucleocapsid (N) gene. Four different genotypes, B3, D4, D5 and D9 were identified including two variants of the D4 genotype. In combination with the epidemiological data four clusters of measles cases and three sporadic cases were revealed. Our study showed that measles in Denmark resulted from imported measles virus strains. The limited duration and short chain of transmission of the identified clusters ascertain that the interruption of measles virus circulation is being sustained. However, measles transmission still has a potential to occur. To minimise the development of pools of susceptible individuals high (>/=95%) routine vaccination coverage with two doses of measles-containing vaccine needs to be attained. Molecular epidemiological studies have proved to be both a useful and a necessary component of an enhanced surveillance system required in the measles elimination phase.

Respiratory diphtheria among highly vaccinated military trainees in Latvia: improved protection from DT compared with Td booster vaccination.

An outbreak of respiratory diphtheria occurred among highly-vaccinated trainees at a Latvian military academy in August-September 2000. We reviewed immunization, clinical and laboratory records and administered a questionnaire to obtain data on exposure factors. Among 207 trainees, 45 (22%) diphtheria cases and 79 (38%) carriers of toxigenic Corynebacterium diphtheriae were identified. All patients survived; 1 had severe myocarditis. Sharing cups was a risk factor for infection. Over 85% of trainees had received > or =5 doses of diphtheria toxoid. Neither infection nor disease was associated with the number of doses or interval since last dose. However, the risk of disease was lower and diphtheria antitoxin levels were higher among trainees who received their last booster dose with higher-antigen diphtheria toxoid (DT) instead of lower-antigen Td. Outbreaks of mild diphtheria can occur among highly-vaccinated persons living in crowded conditions with intense exposure; high-antigen diphtheria booster-vaccination might provide better protection under these conditions.

[An outbreak of measles in the county of Northern Jutland]. / Et udbrud af maeslinger i Nordjylland.

INTRODUCTION: With the introduction of MMR vaccination in the childhood vaccination programme in 1987, measles in Denmark is now rare. However, sub-optimal vaccination coverage results in the accumulation of susceptibles and outbreaks may still occur. MATERIAL AND METHODS: Information from epidemiological investigations and experience gained from the management of measles cases in a children's ward in Aalborg Hospital are described. RESULTS: A nine-year-old child was admitted with a tentative diagnosis of travel associated clinical malaria. The patient was not isolated and information on possible exposure to measles was only obtained upon discharge. Laboratory confirmation was received ten days after admission. At this time, a previous close-contact patient was re-admitted with high grade fever. This second patient was isolated following laboratory confirmation, and other hospitalised children received passive immunization. A total of 24 cases were reported, of which 12 patients were infected whilst hospitalisation and 21 were unvaccinated against measles. DISCUSSION: In a sub-optimally immunized population the introduction of measles virus may cause an outbreak in a local setting including a hospital environment, with potential spread to other geographical areas and hospitals. Obtaining a history of possible exposure to childhood infections, irrespective of the vaccination status, becomes highly significant upon admission. In the case of measles a detailed travel history is essential.