Using genomics to examine the persistence of Streptococcus pneumoniae serotype 19A in Ireland and the emergence of a sub-clade associated with vaccine failures.

BACKGROUND: Streptococcus pneumoniae serotype 19A remains a significant cause of invasive pneumococcal disease (IPD) in Ireland despite the successful introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 which reduced the overall incidence of IPD in children. METHODS: Invasive Streptococcus pneumoniae serotype 19A isolates from the Irish reference laboratory between 2007-08 and 2017-18 were analysed using whole genome sequencing (WGS) to investigate the persistence of this vaccine-preventable serotype. We compared the entire national 19A collection to other international collections using a standardised nomenclature of Global Pneumococcal Sequencing Clusters (GPSC). RESULTS: Expansion of GPSCs and clonal complexes (CCs) may have been associated with vaccine introduction and antimicrobial prescribing policies. A sub-clade of GPSC1-CC320 (n = 25) unique to Ireland, included five of the ten vaccine failures/breakthrough cases identified (p = 0.0086). This sub-clade was not observed in a global GPSC1-CC320 collection. All isolates within the sub-clade (n = 25) contained a galE gene variant rarely observed in a global pneumococcal collection (n = 37/13454, p < 0.001) nor within GPSC1-CC320 (n = 19/227) (p < 0.001). The sub-clade was estimated to have emerged at the start of the PCV-vaccine era (ancestral origin 2000, range 1995-2004) and expanded in Ireland, with most isolated after PCV13 introduction (n = 24/25). CONCLUSIONS: The identification of a sub-clade/variant of serotype 19A highlights the benefit of using WGS to analyse genotypes associated with persistence of a preventable serotype of S. pneumoniae. Particularly as this sub-clade identified was more likely to be associated with IPD in vaccinated children than other 19A genotypes. It is possible that changes to the galE gene, which is involved in capsule production but outside of the capsular polysaccharide biosynthesis locus, may affect bacterial persistence within the population. Discrete changes associated with vaccine-serotype persistence should be further investigated and may inform vaccine strategies.

Determinants of influenza and pertussis vaccine uptake in pregnant women in Ireland: A cross-sectional survey in 2017/18 influenza season.

In Ireland seasonal influenza and pertussis vaccination during pregnancy is recommended and every year national campaigns are organised to raise awareness and improve uptake. We estimated influenza and pertussis vaccine uptake and identified factors associated with vaccination status in pregnant women in 2017/18. We conducted a face-to-face omnibus survey, with quota sampling, among women aged 18-55 years and collected socio-demographic characteristics, self-reported vaccination status, awareness of vaccine campaigns, and attitudes towards vaccination. Sample was weighted to ensure representativeness with the target population. We performed univariate and multivariable logistic regression analyses on survey data. Overall, 241 pregnant women were enrolled. Influenza and pertussis vaccine uptake was 61.7% and 49.9%, respectively. Awareness of vaccine campaign and socio-economic status (SES) were associated with both influenza and pertussis vaccine uptake. The association between SES and uptake of vaccines differed by awareness. Women aware of the influenza vaccine campaign and with mid and low SES were less likely to be vaccinated, compared to those with high SES (aOR = 0.46; 95%CI: 0.22-0.97; aOR = 0.27; 95%CI: 0.12-0.60, respectively); women not aware of the pertussis vaccine campaign and with mid and low SES were less likely to be vaccinated, compared to those aware and with high SES (aOR = 0.15; 95%CI: 0.04-0.48; aOR = 0.05; 95%CI: 0.01-0.24, respectively). General practitioner (GP) recommendation was the main reason for receiving influenza vaccine (39.2%), and 71.8% of women were recommended pertussis vaccination from their GPs. The survey reports moderate uptake of vaccines among pregnant women, inequalities in uptake by SES and identifies GPs as primary source for vaccine recommendation. We recommend multifaceted campaigns, by engaging GPs, to target all socio-economic groups.

Is It Time To Review The Vaccination Strategy To Protect Adults Against Invasive Pneumococcal Disease?

Pneumococcal conjugate vaccines (PCVs) have reduced the predominant serotypes causing invasive pneumococcal disease (IPD). We assessed the impact of the paediatric 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) among older adults. We compared serotype-specific incidence rates from 2007/08 to 2016/17, expressed as incidence rate ratios (IRR). Introducing PCV7 and PCV13 into the childhood immunisation programme resulted in a decline in these serotypes in adults ≥65 years of age, with PCV7 serotypes decreasing by 85% (IRR=0.11, 95%CI: 0.05-0.22, p<0.0001) and PCV13 serotypes not included in PCV7 (PCV13-7), decreasing by 9% (IRR=0.68, 95%CI: 0.40-1.16, p=0.134). However, there was a significant increase in serotypes only found in the 23-valent polysaccharide vaccine, PPV23-PCV13: IRR=2.57, 95%CI: 1.68-4.03, p<0.0001, and non-vaccine types (NVTs), IRR=3.33, 95%CI: 1.75-6.84, p=0.0001. The decline of IPD associated with PCV7/13 serotypes and the increase in PPV23-PCV13 serotypes indicates clear serotype replacement. Increasing PPV23 uptake could still reduce the burden of disease for this population.

The epidemiology of invasive pneumococcal disease in older adults in the post-PCV era. Has there been a herd effect?

The 7 and 13-valent pneumococcal conjugate vaccines (PCVs) have reduced the incidence of invasive pneumococcal disease (IPD) in children in many countries. The objective of this work was to assess the impact of PCVs and potential herd-protection in older adults in Ireland. IPD notification and typing data from adults ⩾65 years of age from July 2007 to June 2016 was assessed using national surveillance data. There was a 94% reduction in PCV7 serotypes from 2007-2008 to 2015-2016, incidence rate ratio (IRR 0·05, P < 0·0001). However, there was no decline in the additional PCV13 (PCV13-7) serotypes over the same period (IRR 0·90) nor in comparison with the pre-PCV13 period 2009-2010 (IRR 0·92). The incidence of serotypes in the 23-valent pneumococcal polysaccharide vaccine only (PPV23-PCV13) and non-vaccine types (NVTs) increased significantly (IRR 2·17, P = 0·0002 and IRR 3·43, P = 0·0001 respectively). Consequently, the overall IPD incidence rate in adults has remained relatively unchanged (from 28·66/100 000 to 28·88/100 000, IRR 1·01, P = 0·9477). Serotype 19A and NVTs were mainly responsible for penicillin resistance in recent years. The decline of PCV7 serotypes indicate that the introduction of PCV7 resulted in herd-protection for adults. However, increases in PPV23-PCV13 and NVTs suggest that changes in vaccination strategy amongst older adults are needed to build on the success of PCVs in children.

Decrease in the Uptake of Seasonal Influenza Vaccine in Persons Aged 65 Years and Older In Ireland since the 2009 Influenza A (H1N1) Pdm09 Pandemic.

In Ireland, there is year-on-year variation in the seasonal influenza vaccine uptake for people aged 65 years and older. We obtained aggregate vaccine uptake data (2004/05-2014/15) by area and age group and applied the 2011 relative deprivation score and GP-density by area. Using Poisson regression model, we estimated the associations between those variables and uptake before and after the 2009 pandemic. After adjusting for age, deprivation status and GP-density, overall persons aged ?65 years were less likely to receive the vaccine after the pandemic compared to before (RR=0.89, 95%CI: 0.82-0.96). Uptake increased with age; both those in the 70-74 and ?75 year age groups were more likely to receive the vaccine compared to those aged 65-69 years (RR=1.18, 95%CI:1.14-1.24; RR=1.34, 95%CI:1.28-1.39 respectively). Qualitative studies should be undertaken to explore whether changes in public perception on risks of the disease and the vaccine and/or public funding and policy influenced the uptake.

Seasonal influenza immunisation in Europe. Overview of recommendations and vaccination coverage for three seasons: pre-pandemic (2008/09), pandemic (2009/10) and post-pandemic (2010/11).

Since 2008, annual surveys of influenza vaccination policies, practices and coverage have been undertaken in 29 European Union (EU)/ European Economic Area (EEA) countries. After 2009, this monitored the impact of European Council recommendation to increase vaccination coverage to 75% among risk groups. This paper summarises the results of three seasonal influenza seasons: 2008/09, 2009/10 and 2010/11. In 2008/09, 27/29 countries completed the survey; in 2009/10 and 2010/11, 28/29 completed it. All or almost all countries recommended vaccination of older people (defined as those aged ≥50, ≥55, ≥59, ≥60 or ≥65 years), and people aged ≥6 months with clinical risk and healthcare workers. A total of 23 countries provided vaccination coverage data for older people, but only 7 and 10 had data for the clinical risk groups and healthcare workers, respectively. The number of countries recommending vaccination for some or all pregnant women increased from 10 in 2008/09 to 22 in 2010/11. Only three countries could report coverage among pregnant women. Seasonal influenza vaccination coverage during and after the pandemic season in older people and clinical groups remained unchanged in countries with higher coverage. However, small decreases were seen in most countries during this period. The results of the surveys indicate that most EU/EEA countries recommend influenza vaccination for the main target groups; however, only a few countries have achieved the target of 75% coverage among risk groups. Coverage among healthcare workers remained low.

Influenza A(H1N1)pdm09 vaccination policies and coverage in Europe.

In August 2010 the Vaccine European New Integrated Collaboration Effort (VENICE) project conducted a survey to collect information on influenza A(H1N1)pdm09 vaccination policies and vaccination coverage in the European Union (EU), Norway and Iceland. Of 29 responding countries, 26 organised national pandemic influenza vaccination and one country had recommendations for vaccination but did not have a specific programme. Of the 27 countries with vaccine recommendations, all recommended it for healthcare workers and pregnant women. Twelve countries recommended vaccine for all ages. Six and three countries had recommendations for specific age groups in children and in adults, countries for specific adult age groups. Most countries recommended vaccine for those in new risk groups identified early in the pandemic such as morbid obese and people with neurologic diseases. Two thirds of countries started their vaccination campaigns within a four week period after week 40/2009. The reported vaccination coverage varied between countries from 0.4% to 59% for the entire population (22 countries); 3% to 68% for healthcare workers (13 countries); 0% to 58% for pregnant women (12 countries); 0.2% to 74% for children (12 countries). Most countries identified similar target groups for pandemic vaccine, but substantial variability in vaccination coverage was seen. The recommendations were in accordance with policy advice from the EU Health Security Committee and the World Health Organization.

The current state of introduction of human papillomavirus vaccination into national immunisation schedules in Europe: first results of the VENICE2 2010 survey.

The Venice 2 human papillomavirus vaccination survey evaluates the state of introduction of the HPV vaccination into the national immunisation schedules in the 29 participating countries. As of July 2010, 18 countries have integrated this vaccination. The vaccination policy and achievements vary among those countries regarding target age groups, delivery infrastructures and vaccination coverage reached. Financial constraints remain the major obstacle for the 11 countries who have not yet introduced the vaccination.

Differences in national influenza vaccination policies across the European Union, Norway and Iceland 2008-2009.

In 2009 the second cross-sectional web-based survey was undertaken by the Vaccine European New Integrated Collaboration Effort (VENICE) project across 27 European Union (EU) member states (MS), Norway and Iceland (n=29) to determine changes in official national seasonal influenza vaccination policies since a survey undertaken in 2008 and to compare the estimates of vaccination coverage between countries using data obtained from both surveys. Of 27 responding countries, all recommended vaccination against seasonal influenza to the older adult population. Six countries recommended vaccination of children aged between six months and <18 years old. Most countries recommended influenza vaccination for those individuals with chronic medical conditions. Recommendations for vaccination of healthcare workers (HCW) in various settings existed in most, but not all countries. Staff in hospitals and long-term care facilities were recommended vaccination in 23 countries, and staff in out-patient clinics in 22 countries. In the 2009 survey, the reported national estimates on vaccine coverage varied by country and risk group, ranging from 1.1% - 82.6% for the older adult population; to between 32.9% -71.7% for clinical risk groups; and from 13.4% -89.4% for HCW. Many countries that recommend the influenza vaccination do not monitor the coverage in risk groups. In 2008 and 2009 most countries recommended influenza vaccination for the main risk groups. However, despite general consensus and recommendations for vaccination of high risk groups, many countries do not achieve high coverage in these groups. The reported vaccination coverage still needs to be improved in order to achieve EU and World Health Organization goals.

Implementation of a national electronic reporting system in Lithuania.

Electronic reporting systems improve the quality and timeliness of the surveillance of communicable diseases. The aim of this paper is to present the process of the implementation and introduction of an electronic reporting system for the surveillance of communicable diseases in Lithuania. The project which started in 2002 was performed in collaboration between Lithuania and Sweden and was facilitated by the parallel process of adapting the surveillance system to European Union (EU) standards. The Lotus-based software, SmittAdm, was acquired from the Department of Communicable Diseases Control and Prevention of Stockholm County in Sweden and adopted for Lithuania, resulting in the Lithuanian software, ULISAS. A major advantage of this program for Lithuania was the possibility to work offline. The project was initiated in the two largest counties in Lithuania where ULISAS had been installed and put in use by January 2005. The introduction was gradual, the national level was connected to the system during late 2005, and all remaining counties were included during 2006 and 2007. The reporting system remains to be evaluated concerning timeliness and completeness of the surveillance. Further development is needed, for example the inclusion of all physicians and laboratories and an alert system for outbreaks. The introduction of this case-based, timely electronic reporting system in Lithuania allows better reporting of data to the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) compared to the former reporting system with paper-based, aggregated data.

National seasonal influenza vaccination survey in Europe, 2008.

A cross-sectional survey was undertaken with the European Union (EU) Member States and Norway and Iceland to describe seasonal influenza immunisation in the 2006-7 season, in particular to identify country-specific recommendations for risk groups, obtain vaccine uptake information and allow comparison with global recommendations. A standardised questionnaire was completed electronically by each country's project gatekeeper. Of the 29 countries surveyed, 28 recommended seasonal influenza vaccination for older age groups (22 for those aged > 65 years), and in one country vaccine was recommended for all age groups. All countries recommended vaccinating patients with chronic pulmonary and cardiovascular diseases and most countries advised to immunise patients with haematologic or metabolic disorders (n=28), immunologic disorders (n=27) and renal disease (n=27), as well as residents of long-term care facilities (n=24). Most countries recommended vaccination for staff in hospitals (n=25), long-term care facilities (n=25) and outpatient clinics (n=23), and one-third had such recommendations for workers in essential (n=10), military (n=10) and veterinary services (n=10) and poultry industry (n=13). Eight countries recommended vaccine for pregnant women; and five advised to vaccinate children (with age limits ranging from 6 months to 5 years). Twenty countries measured influenza vaccine uptake among those aged > 65 years (range 1.8%-82.1%), seven reported uptake in healthcare workers (range 14%-48%) and seven assessed coverage in persons with underlying medical conditions (range 27.6%-75.2%). The data provided by this study can assist EU states to assess and compare their influenza vaccination programme performance with other countries. The information provides a comprehensive overview of policies and programmes and their outcomes and can be used to inform joint discussions on how the national policies in the EU might be standardised in the future to achieve optimal coverage. Annual surveys could be used to monitor changes in these national policies.

Risk groups and uptake of influenza and pneumococcal vaccine in Ireland.

In Ireland, influenza and pneumococcal vaccines are recommended for adults aged 65 years and over and for those with chronic illness or immunosuppression. Influenza vaccine is recommended for healthcare workers (HCWs) and residents of long stay care facilities. Influenza vaccine uptake is only available for those aged 65 years and over. We conducted a survey to estimate the size of risk groups between 18 and 64 years of age, influenza and pneumococcal vaccine uptake in this group, and to determine possible factors influencing vaccine uptake to improve targeted immunisation programmes. Among respondents aged 18-64 years, 136 of 1,218 (11%) belonged to a health risk group; uptake of influenza and pneumococcal vaccine in these risk groups was 28% (95% CI: 20.9-35.4) and 11% (95% CI: 6.7-17.2) respectively. Uptake among persons aged over 65 years was 69% (95% CI: 62.2-74.4) and 41% (95% CI: 35.0-47.9) for influenza and pneumococcal vaccine, respectively. Influenza vaccine uptake among HCWs was 20% (95% CI: 13.1-28.7). Half (47.6%) of influenza-vaccinated respondents reported that their family doctor had recommended it; 60% of non-vaccinated respondents, for whom influenza vaccine was indicated, saw themselves at low risk of influenza.