Economic Evaluation of Selective Neonatal Bacillus Calmette-Guérin Vaccination of High-risk Infants in Ireland.

BACKGROUND: In Western Europe, currently only Ireland and Portugal continue to provide universal neonatal bacillus Calmette-Guérin (BCG) vaccination programs, despite not being considered as high tuberculosis (TB) incidence countries. Other European countries only vaccinate infants considered at high risk of contracting TB. We evaluated the cost-effectiveness of selective BCG vaccination compared with strategies of universal and no vaccination. METHODS: An economic model was used to simulate a cohort from birth to life expectancy, taking the perspective of the publicly funded healthcare system. BCG protection was modeled to last 15 years. International vaccine efficacy data were combined with Irish epidemiologic and cost data. The model took into account long-term sequelae associated with TB meningitis and severe adverse reactions relating to the BCG vaccine. A fully probabilistic model was used to incorporate uncertainty across all parameters. RESULTS: At &OV0556;139,557 per quality-adjusted life year, selective vaccination was not cost-effective relative to a program of no vaccination. The incremental cost-effectiveness of universal vaccination was &OV0556;2.55 million per quality-adjusted life year relative to selective vaccination. There was substantial uncertainty regarding the effectiveness of BCG vaccination. The cost-effectiveness of selective vaccination could be substantially improved by reducing the cost of administering the vaccine. CONCLUSIONS: In the absence of changes to other aspects of TB control, a switch to selective vaccination will result in increased cases of childhood TB. Although not considered cost-effective, selective vaccination may be preferable to no vaccination until other changes to TB control may be implemented to reduce the risk of TB in children.

Tuberculosis contact investigations associated with air travel in Ireland, September 2011 to November 2014.

The risk of communicable disease transmission during air travel is of public health concern and has received much attention over the years. We retrospectively reviewed information from nine flights (≥ 8 hours) associated with infectious tuberculosis (TB) cases in Ireland between September 2011 and November 2014 to investigate whether possible transmission had occurred. Twenty-four flights notified in Ireland associated with sputum smear-positive pulmonary TB cases with a history of air travel were reviewed. Nine were suitable for inclusion and analysed. Six cases of infectious TB travelled on nine flights. A total of 232 passengers were identified for contact tracing; 85.3% (n = 198) had sufficient information available for follow-up. In total, 12.1% (n = 24) were reported as screened for TB. The results revealed no active TB cases among passengers and 16.7% (n = 4) were diagnosed with latent TB infection (LTBI) all of whom had other risk factors. Despite the limited sample size, we found no evidence of M. tuberculosis transmission from infectious passengers. This study identified challenges in obtaining complete timely airline manifests, leading to inadequate passenger information for follow-up. Receipt of TB screening results from international colleagues was also problematic. The challenge of interpreting the tuberculin skin test results in determining recent vs earlier infection was encountered.

Evaluating the neonatal BCG vaccination programme in Ireland.

BACKGROUND: The aim of this study was to compare the cost effectiveness of the current Irish programme of universal BCG vaccination of infants versus a programme which considered selectively vaccinating high risk infants using decision analytical modelling. METHODS: The efficacy of the BCG vaccine was re-evaluated to inform a decision analytical model constructed to follow a birth cohort of vaccinated and unvaccinated infants over a 15 year time horizon. The number of life years gained (LYG) was the primary outcome measure and this was compared to the net cost of the vaccination strategies. RESULTS: In the base case analysis, the incremental cost effectiveness ratios (ICERs) for the universal strategy and selective strategy vs no vaccination were €204,373/LYG and €143,233/LYG respectively. When comparing the incremental difference in moving from the universal to the selective strategy, the selective strategy costs €1,055,692 less per 4.8 life years lost per birth cohort. One way sensitivity analyses highlighted that a move from the universal to the selective strategy was particularly sensitive to the estimate of vaccine efficacy against deaths, the cost of administering the vaccine and the multiplier used to apportion risk of contracting tuberculosis. Probabilistic analysis suggested that a move from a universal based strategy to a selective based strategy could be deemed cost effective (probability of cost effectiveness is 76.8 %). CONCLUSION: The results of the study support the protective effect of the BCG vaccine in infants and quantified the cost effectiveness of the current BCG vaccination strategy and the decremental difference in moving to a selective strategy. This analysis highlights that the additional protection offered by the universal vaccination strategy is small compared to that of the selective strategy. Consideration should therefore be given to the implementation of a selective vaccination strategy, and diverting resources to improve TB case management and control.

Low vaccination coverage for seasonal influenza and pneumococcal disease among adults at-risk and health care workers in Ireland, 2013: The key role of GPs in recommending vaccination.

The World Health Organization (WHO), and European Agencies recommend influenza vaccination for individuals at-risk due to age (≥65 years), underlying diseases, pregnancy and for health care workers (HCWs) in Europe. Pneumococcal vaccine is recommended for those at-risk of pneumococcal disease. In Ireland, vaccination uptake among at-risk adults is not routinely available. In 2013, we conducted a national survey among Irish residents ≥18 years of age, to estimate size and vaccination coverage of at-risk groups, and identify predictive factors for influenza vaccination. We used computer assisted telephone interviews to collect self-reported information on health, vaccination status, attitudes towards vaccination. We calculated prevalence and prevalence ratios (PR) using binomial regression. Overall, 1770 individuals participated. For influenza, among those aged 18-64 years, 22% (325/1485) [95%CI: 17%-20%] were at-risk; 28% [95%CI: 23%-33%] were vaccinated. Among those aged ≥65 years, 60% [95%CI: 54%-66%] were vaccinated. Influenza vaccine uptake among HCWs was 28% [95%CI: 21%-35%]. For pneumococcal disease, among those aged 18-64 years, 18% [95%CI: 16%-20%] were at-risk; 16% [95%CI: 12%-21%] reported ever-vaccination; among those aged ≥65 years, 36% [95%CI: 30%-42%] reported ever-vaccination. Main reasons for not receiving influenza vaccine were perceptions of not being at-risk, or not thinking of it; and among HCWs thinking that vaccination was not necessary or they were not at-risk. At-risk individuals were more likely to be vaccinated if their doctor had recommended it (PR 3.2; [95%CI: 2.4%-4.4%]) or they had access to free medical care or free vaccination services (PR 2.0; [95%CI: 1.5%-2.8%]). Vaccination coverage for both influenza and pneumococcal vaccines in at-risk individuals aged 18-64 years was very low. Influenza vaccination coverage among individuals ≥65 years was moderate. Influenza vaccination status was associated with GP vaccination recommendation and free access to vaccination services. Doctors should identify and recommend vaccination to at-risk patients to improve uptake.

Reliable surveillance of tick-borne encephalitis in European countries is necessary to improve the quality of vaccine recommendations.

In July-November 2009, 26 European Union (EU) Member States (MSs), Norway and Iceland, participated in a survey seeking information on national tick-borne encephalitis (TBE) vaccination recommendations. Information on TBE surveillance, methods used to ascertain endemic areas, vaccination recommendations, vaccine coverage and methods of monitoring of vaccine coverage were obtained. Sixteen countries (57%) reported presence of TBE endemic areas on their territory. Vaccination against TBE was recommended for the general population in 8 (28%) countries, for occupational risk groups - in 13 (46%) countries, and for tourists going abroad - in 22 (78%) countries. Although vaccination recommendations for country residents, and for tourists always referred to endemic areas, there was no uniform, standardized method used to define endemic areas. For this reason, clear recommendations for tourists need to be developed, and standardized surveillance directed to efficient assessment of TBE risk need to be implemented in European countries.

Epidemiology, clinical characteristics and resource implications of pandemic (H1N1) 2009 in intensive care units in Ireland.

OBJECTIVE: To describe the incidence, clinical characteristics and outcomes of critically ill patients in Ireland with pandemic (H1N1) 2009 infection, and to provide a dynamic assessment of the burden of such cases on Irish intensive care units. DESIGN, SETTING AND PARTICIPANTS: Multicentre prospective observational study of all adult patients admitted to any of the 30 ICUs in the Republic of Ireland between 15 July 2009 and 30 May 2010. MAIN OUTCOME MEASURES: Patient demographics, clinical characteristics and ICU mortality; ICU admissions, bed-days, bed occupancy rates and distribution. RESULTS: Seventy-seven adult patients with pandemic (H1N1) 2009 infection were admitted to 27 of 30 Irish ICUs. The median age was 43 years (IQR, 30-56 years); 67 patients (88%) were aged under 65; 39 (51%) were male. Sixty-two patients (82%) had comorbid conditions, including obesity (36%), respiratory disease (34%) and malignancy or immunosuppression (20%). Eight (11%) were pregnant, and 27 (36%) were smokers. Sixty-seven patients were mechanically ventilated, 24 (32%) required renal replacement therapy, 39 (51%) received vasopressors and four (5%) received extracorporeal membrane oxygenation. Of 14 patients (18%) who died in the ICU, two had no pre-existing comorbidities. The ICU admission rate of patients with pandemic (H1N1) 2009 infection was 22.5/million population. A total of 1882 ICU bed-days (557.5 bed-days/million adult population) were consumed, equating to a 3.9% bed occupancy rate, with a peak of 14.0% in October 2009. Median length of stay was 12 days (IQR, 7-34 days). CONCLUSION: The 2009 influenza A (H1N1) pandemic was a significant burden on Irish ICUs, predominantly affecting the tertiary centres. The demographics and clinical characteristics were similar to those described in the southern hemisphere, suggesting such data may inform future resource planning for similar threats.

Varicella infection and the impact of late entry into the Irish healthcare system.

We present a case which highlights several areas of concern relating to the prevention and management of varicella in Ireland. We review the pathophysiology of this virus and highlight its greater potential for morbidity in certain groups, most particularly adult males. The experience and opinions with regard to varicella vaccination in the US and other temperate countries is reviewed along with evidence of changing epidemiology of varicella infection. The National Immunisation Advisory Committee (NIAC) guidelines are reviewed in the context of our experience.

Hepatitis B immunisation programmes in European Union, Norway and Iceland: where we were in 2009?

In January 2009 25 European Union (EU) Member States (MSs), Norway and Iceland, participated in a survey seeking information on national hepatitis B vaccination programmes. Details of vaccination policy, schedule, population groups targeted for vaccination, programme funding, vaccine coverage and methods of monitoring of vaccine coverage were obtained. Twenty (74%) countries reported that they have a universal hepatitis B vaccination programme, in addition to immunisation of at risk groups; seven (26%) countries recommend HBV for high risk groups only (with some inter-country variation on groups considered at high risk). Among countries without universal hepatitis B vaccination programmes, the major factor for non-introduction is low disease endemicity.

Development of a real-time RT-PCR for the detection of swine-lineage influenza A (H1N1) virus infections.

BACKGROUND: A novel influenza A virus, subtype H1N1 of swine-lineage (H1N1 swl) has transmitted rapidly to many regions of the world with evidence of sustained transmission within some countries. Rapid detection and differentiation from seasonal influenza is essential to instigate appropriate patient and public health management and for disease surveillance. OBJECTIVES: To develop a rapid and sensitive real-time reverse transcriptase polymerase chain reaction (rtRT-PCR) for confirmation of H1N1 swl. STUDY DESIGN: A one-step rtRT-PCR approach was employed to target the matrix gene of the novel influenza A/H1N1 swl and validated against a panel of seasonal influenza A (H1N1 and H3N2), swine influenza A/H1N1 and avian influenza A/H5N1 viruses. The assay following validation was then used prospectively to detect H1N1 swl positive specimens from the recent outbreaks in the UK and the Republic of Ireland. RESULTS: The one-step H1N1 swl matrix rtRT-PCR successfully detected H1N1 swl clinical specimens and did not cross-react with seasonal influenza A, subtypes H1N1 and H3N2 viruses and swine influenza A (H1N1). The H1N1 swl matrix assay did cross react with H5N1. The H1N1 swl matrix assay was then compared to two other assays using a dilution series and a panel of untyped influenza A positive clinical samples. These experiments found the assay to have a comparable sensitivity to the established universal influenza A rtRT-PCR and was more sensitive than the H1N1 swl specific assay that targeted the H1 region. CONCLUSIONS: The results demonstrate that the rtRT-PCR is sensitive and should be used alongside existing universal influenza A assays to rapidly detect the novel H1N1 swl virus.

Vaccine adverse event monitoring systems across the European Union countries: time for unifying efforts.

A survey conducted among 26 European Countries within the Vaccine European New Integrated Collaboration Effort (VENICE) project assessed the status of organization in prevention and management of adverse events following immunization (AEFI) and level of interconnection, with the aim at individuating points of strength and weakness. The emerging picture is for a strong political commitment to control AEFIs in Member States (MS), but with consistent heterogeneity in procedures, regulations and capacity of systems to collect, analyze and use data, although with great potentialities. Suggestions are posed by authors to promote actions for unifying strategies and policies among MS.

European Sero-Epidemiology Network 2: standardisation of immunoassay results for pertussis requires homogeneity in the antigenic preparations.

A standardisation process, already developed during the earlier European Sero-Epidemiology Network (ESEN) project, was employed with a more robust algorithm to harmonise results of pertussis serological assays performed in 12 European and non-European countries. Initially, results from each country's own assay were compared with those obtained at the reference laboratory by means of an in-house pertussis toxin (PT)-based ELISA: seven countries used in-house or commercial PT-ELISAs; the other countries used assays based on Bordetella pertussis whole cell extracts (WCE) (three countries) or on combined PT-FHA (filamentous haemagglutinin) antigenic preparations (two countries). The WCE assays, although admitted for diagnostic purposes, confirmed their low correlation with the PT-ELISAs and their results could not be used for standardisation; the PT-FHA ELISAs gave results that were suitable for standardisation in one country but unsatisfactory in the other; the use of purified PT in serological assays confirmed its better reliability than other preparations and all PT-ELISAs results could be calibrated against those of the reference centre. In the standardisation process two high-titre cut-offs indicative of likelihood of recent infection (from within 4 weeks of disease onset up to 1 year after) were included for evaluations as they are suggested to be more useful, for the sero-epidemiological assays of immunity to pertussis, than the cut-off of protection, commonly employed, but still not defined for pertussis. Providing PT-ELISAs are used, standardisation of pertussis assay results is always possible and, when standardisation is performed, evaluation and comparison of the impact of different interventions can be also allowed, by measuring at the distribution of high antibody titres in the populations.

Economic evaluation of a universal childhood pneumococcal conjugate vaccination strategy in Ireland.

OBJECTIVE: To evaluate the cost-effectiveness of implementing a universal infant 7-valent pneumococcal conjugate vaccine (PCV7) vaccination program in the Irish health-care setting from the health-care payers' perspective. METHODS: A model was constructed in MS Excel to follow a cohort of vaccinated and unvaccinated individuals from birth over a 5-year period. The reduction in events that would be associated with PCV7 vaccination and the mortality and cost resulting from these events were analyzed. In a separate submodel, the effect of herd immunity was investigated. RESULTS: Implementing a PCV7 vaccine program in Ireland in a birth cohort of 61,000 infants would be expected to prevent 7703 cases of pneumococcal-related infections over 5 years, resulting in costs avoided of 2.05 million euros increasing to 4.6 million euros if the effect of herd immunity was included. The baseline incremental cost-effectiveness ratio was 249,591 euros/life years gained (LYG), which reduced to 5997 euros/LYG when the effect of herd immunity was included. CONCLUSIONS: A universal infant pneumococcal conjugate vaccination could be considered highly cost-effective in the Irish health-care setting from a health-care payers' perspective, if viewed in terms of the herd immunity effect. The results of this study have positive ramifications for countries in the early stages of health technology assessment.

Comparison of rubella seroepidemiology in 17 countries: progress towards international disease control targets.

OBJECTIVE: To standardize serological surveillance to compare rubella susceptibility in Australia and 16 European countries, and measure progress towards international disease-control targets. METHODS: Between 1996 and 2004, representative serum banks were established in 17 countries by collecting residual sera or community sampling. Serum banks were tested in each country and assay results were standardized. With a questionnaire, we collected information on current and past rubella vaccination programmes in each country. The percentage of seronegative (< 4 IU/ml) children (2-14 years of age) was used to evaluate rubella susceptibility, and countries were classified by seronegativity as group I (< 5%), group II (5-10%) or group III (> 10%). The proportion of women of childbearing age without rubella protection (< or = 10 IU/ml) was calculated and compared with WHO targets of < 5%. FINDINGS: Only Romania had no rubella immunization programme at the time of the survey; the remaining countries had a two-dose childhood schedule using the measles, mumps and rubella (MMR) vaccine. The percentage of susceptible children defined five countries as group I, seven as group II and four as group III. Women of childbearing age without rubella protection were < 5% in only five countries. CONCLUSION: Despite the low reported incidence in many countries, strengthening the coverage of the routine two-dose of MMR vaccine among children is needed, especially in group III countries. Catch-up campaigns in older age groups and selective targeting of older females are needed in many countries to ensure necessary levels of protective immunity among women of childbearing age.

Cost effectiveness of hepatitis B vaccination strategies in Ireland: an economic evaluation.

BACKGROUND: In accordance with World Health Organization recommendations, many European countries have introduced universal hepatitis B vaccination policies. The UK and Ireland are exceptions. In this study, we conducted an economic evaluation of a universal infant hepatitis B vaccination programme, using a six-component vaccine, compared with the current selective strategy of vaccinating high-risk infants with a monovalent hepatitis B vaccine. METHODS: A cost effectiveness analysis was conducted using a Markov model. The perspective of the analysis was the Irish Health Service Executive. Unit cost and resource utilization data were derived from expert clinical opinion, published sources, diagnosis-related group costs for hospital admissions and local cost estimates for medical fees and laboratory investigations. A full probabilistic sensitivity analysis was undertaken. Both costs and outcomes were modelled over a period of 80 years and discounted at 3.5%. RESULTS: Assuming an incidence of acute hepatitis B virus (HBV) infection in Ireland of 8.4 per 100,000 population, the incremental cost effectiveness ratio ranged from euro10,992/life years gained (LYG) to euro67 200/LYG, at the lowest and highest price estimates for the six-component vaccine, respectively. The cost effectiveness of universal versus selective hepatitis B vaccination was sensitive to the risk of acute HBV infection, the cost of the universal infant vaccination programme and the discount rate. CONCLUSION: At a cost of euro29.00 per dose of the six-component vaccine, universal infant hepatitis B vaccination is cost effective at euro37 018/LYG. This compares favourably with other preventive programmes in Ireland.

Hepatitis B reactivation in an Irish dialysis unit, 2005.

In April 2005, a case of reactivation of hepatitis B virus (HBV) infection occurred in a patient undergoing haemodialysis in an Irish hospital. This incident potentially affected patients attending hospitals throughout the country, so a national incident team was set up coordinate the response to the incident.A total of 306 dialysis patients, attending 17 different dialysis centres (14 in Ireland), were identified as having been potentially exposed to HBV as a result of this incident. A programme of HBV serological testing and HBV vaccination was instituted. There was no evidence that any patient acquired HBV infection as a result of cross-infection from the index patient, although 11 patients (3.6%) had evidence of past infection (anti-HBc positive, HBsAg negative). The majority of patients in this cohort were of unknown HBV vaccination status (62.7%), 13.4% were fully vaccinated, 4.6% partially vaccinated and 15.7% unvaccinated. Of 239 tested for anti-HBs, 183 (76.6%) had a titre <10 mIU/ml. Local incidents in dialysis units can have national implications due to the frequent patient transfer between units. This incident highlighted serious deficiencies in current structures and practices, and a lack of appropriate guidelines. However, there were positive outcomes from this incident. The majority of Irish dialysis patients have now been vaccinated against HBV, and lessons learned have been used to develop national guidelines on HBV vaccination and testing and on the management of incidents of blood-borne viral infections in dialysis units.