Effectiveness of a vaccination programme for an epidemic of meningococcal B in New Zealand

New Zealand has experienced a prolonged epidemic of meningococcal B disease since 1991. The epidemic has waned significantly since its most recent peak in 2001. A strain-specific vaccine, MeNZB, was introduced to control the epidemic in 2004, achieving 81% coverage of people under the age of 20. The vaccine was rolled out in a staged manner allowing the comparison of disease rates in vaccinated and unvaccinated individuals in each year.Vaccine effectiveness in people aged under 20 years is estimated using a Poisson regression model in the years 2001-2008, including adjustments for year, season, age, ethnicity, region and socioeconomic status. Further analyses investigate the dose response relationship, waning of the vaccine effect after one year, and cross-protection against other strains of meningococcal disease.The primary analysis estimates MeNZB vaccine effectiveness to be 77% (95% CI 62-85) after 3 doses and a mean follow-up time of 3.2 years. There is evidence for a protective effect after 2 doses 47% (95% CI 16-67), and no evidence for a waning of effectiveness after one year. Simultaneous modelling of invasive pneumococcal disease and epidemic strain meningococcal B suggests a degree of residual confounding that reduces the effectiveness estimate to 68%. There is evidence for some cross-protection of MeNZB against non-epidemic strains.The MeNZB vaccine was effective against the New Zealand epidemic strain of meningococcal B disease. Between July 2004 and December 2008 an estimated 210 epidemic strain cases (95% CI 100-380), six deaths and 15-30 cases of severe sequelae were avoided in New Zealand due to the introduction of the MeNZB vaccine.     

MeNZB: a safe and highly immunogenic tailor-made vaccine against the New Zealand Neisseria meningitidis serogroup B disease epidemic strain

Clinical studies have been conducted in New Zealand evaluating the safety and immunogenicity of an outer membrane vesicle (OMV) vaccine, MeNZB, developed to control epidemic disease caused by group B meningococci, subtype P1.7b,4. MeNZB, administered in a three-dose regimen, was well tolerated and induced a seroresponse, defined as a four-fold rise (> or =titre 8) in serum bactericidal antibodies against the vaccine strain 4-6 weeks after the third vaccination, in 96% (95% confidence interval (CI): 79-100%) of adults, 76% (95% CI: 72-80%) of children, 75% (95% CI: 69-80%) of toddlers and 74% (95% CI: 67-80%) of infants receiving MeNZB. In conclusion, these findings suggest that MeNZB is safe and is likely to confer protection against systemic group B meningococcal disease caused by the epidemic strain.     

Safety review: two outer membrane vesicle (OMV) vaccines against systemic Neisseria meningitidis serogroup B disease

MenBvac is an OMV vaccine against systemic serogroup B Neisseria meningitidis disease. MenBvac was developed for control of a B:15:P1.7,16 subtype epidemic in Norway and administered to 180,000 subjects in 28 clinical studies. MeNZB, a daughter vaccine of MenBvac, was developed for a clonal B:4:P1.7b,4 epidemic in New Zealand and administered to 1 million people <20 years. The vaccines were similar regarding reactogenicity profile. Serious adverse events (SAEs) in general and particularly neurologic SAEs were very rare. Despite frequently reported local reactions and fever in those under 5 years, these OMV-based vaccines containing 25 microg antigen can be considered safe for use in all age groups.     

Evaluating the post-licensure effectiveness of a group B meningococcal vaccine in New Zealand: a multi-faceted strategy

A nationwide strategy to control a group B meningococcal disease epidemic in New Zealand using an epidemic strain-specific vaccine (MeNZB ) commenced in 2004. In the absence of randomised controlled trials investigating the efficacy of this particular vaccine, a complement of observational methods are planned to evaluate the post-licensure effectiveness of this vaccine strategy. The two main approaches involve a Poisson regression model investigating the overall impact of the MeNZB programme on disease rates over time capitalising on detailed population-based disease surveillance data and the staged roll-out of the vaccine campaign, and a case-control study that aims to estimate vaccine effectiveness in pre-school children. The studies are designed to minimise the potential biases inherent in all observational methods and provide critical data on the effectiveness of a major public health intervention.     

Immunogenicity and safety of a strain-specific MenB OMV vaccine delivered to under 5-year olds in New Zealand

To control the devastating group B meningococcal epidemic in New Zealand a strain-specific OMV vaccine (MeNZB) was extensively tested before vaccination of >1,000,000 people under 20 years. After the three-dose course 75% of 6-8-month-old infants and 16-24-month-old toddlers showed four-fold increases in bactericidal antibodies. In 6-10-week-old infants a fourth dose was needed to obtain similar results. After primary vaccination, the antibody titre decline was most pronounced among the youngest but both young infants and toddlers showed a clear booster response to a fourth dose. MeNZB was safe and well tolerated. The comprehensive post-licensure safety surveillance revealed no safety concerns.     

Vaccine Preventability of Meningococcal Clone,Greater Aachen Region,Germany

Emergence of serogroup B meningococci of clonal complex sequence type (ST) 41/44 can cause high levels of disease, as exemplified by a recent epidemic in New Zealand. Multiplication of annual incidence rates (3.1 cases/100,000 population) of meningococcal disease in a defined German region, the city of Aachen and 3 neighboring countries (Greater Aachen) prompted us to investigate and determine the source and nature of this outbreak. Using molecular typing and geographic mapping, we analyzed 1,143 strains belonging to ST41/44 complex, isolated from persons with invasive meningococcal disease over 6 years (2001–2006) from 2 German federal states (total population 26 million) and the Netherlands. A spatially slowly moving clone with multiple-locus variable-number tandem repeat analysis type 19, ST42, and antigenic profile B:P1.7–2,4:F1–5 was responsible for the outbreak. Bactericidal activity in serum samples from the New Zealand MeNZB vaccination campaign confirmed vaccine preventability. Because this globally distributed epidemic strain spreads slowly, vaccination efforts could possibly eliminate meningococcal disease in this area.     

The cost-effectiveness of introducing a varicella vaccine to the New Zealand immunisation schedule.

This study examined the cost-effectiveness of adding a varicella vaccine to an existing childhood immunisation schedule relative to a counterfactual where the varicella vaccine is available on a user-pays basis (the current New Zealand situation). The costs and consequences of chickenpox in an annual cohort of 57,200, 15-month old children were simulated for a 30-year period. The cohort simulation design captures the 'phasing-in' effects of routine varicella vaccination on the population. From a health care payer's perspective (medical costs only) every dollar invested in a vaccination programme would return NZ $0.67. However, from a societal point of view (which includes the value of work-loss), a vaccination programme would return NZ $2.79 for every dollar invested. To implement a varicella vaccination programme covering 80% of 15-month old children in New Zealand would add more than NZ $1 million in net direct (health care) costs each year. However, the indirect cost savings from reduced losses of work-time exceed NZ $2 million annually. The net average health care cost per child vaccinated over the 30-year modelling period was $54 whereas the cost-savings from work-loss averted averaged $101 per child vaccinated. Total cost-savings to society of $47 per child vaccinated, on average, could be gained from a vaccination programme. The finding that the addition to vaccination costs resulting from a routine programme (including the cost of complications from the vaccine) were greater than the offsetting health care cost savings from reduced incidence of chickenpox were robust to a sensitivity analysis on all assumptions within plausible ranges. Overall cost-effectiveness estimates were most sensitive to assumptions regarding lost work-time, the discount rate, and the price and efficacy of the vaccine. Estimates were relatively insensitive to changes in assumptions regarding health care utilisation.     

Hepatitis B: vaccination programmes in Europe--an update

In the eight years since the Global Advisory Group of the Expanded Program on Immunisation set 1997 as the target for integrating hepatitis B (HB) vaccination into national immunisation programs world-wide, more than 116 countries have included HB vaccine as part of their routine infant or adolescent immunisation programs. Meanwhile, many countries have performed economic evaluation studies, while others have initiated sero-epidemiological studies to generate input data for burden of disease calculation. These studies have indicated that epidemiological and economic arguments cannot be used to delay the implementation of universal hepatitis B vaccination. Some countries have improved their surveillance system and included viral hepatitis in the surveillance programs. Other have put hepatitis B vaccination on the political agenda. By the year 2000, following countries of the WHO European Region (51 countries) have implemented a universal hepatitis B immunisation programme: Andorra, Albania, Austria, Belarus, Belgium, Bulgaria, Estonia, France, Germany, Greece, Italy, Israel, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, Luxembourg, Malta, Moldova, Monaco, Poland, Portugal, parts of the Russian Federation, Romania, Slovakia, Slovenia, San Marino, Spain, Switzerland, Turkey and Uzbekistan. The Netherlands and some other European countries are seriously studying the issues or are making budgetary provisions for introduction of HB vaccine into their vaccination programme. Most of the European countries, which now use the vaccine routinely, have started with adolescent or infant immunisation. Belgium (1999), France (1994) and Italy (1991) have begun with both adolescent and infant HB immunisation. France continues since 1st October 1998 with the infant immunisation programme only. The rewards of effective implementation of the programmes in these countries are becoming apparent; and their success offers an exemplary model for other countries. The deadline was 1997. Globally, work still remains to be done to support and implement interventions that will bring us closer to the WHO goal and to control, eliminate and eradicate hepatitis B in the coming generations at large. If all the 145 million infants born in 1991 had been vaccinated in this way, the number of chronic carriers would have been reduced by 7.5 million, and 1.8 million deaths prevented.     

The risk of simple febrile seizures after immunisation with a new group B meningococcal vaccine, New Zealand

As part of safety monitoring during a group B meningococcal disease vaccination campaign in New Zealand, we examined the possible excess risk of vaccine-associated simple febrile seizures (SFS). We conducted a cohort analysis using data from active hospital-based surveillance in the South Auckland area and a national immunisation register. Based on analysis of approximately 63,000 doses, we found no statistically significant increase in SFS incidence within 1, 2, 4, or 7 days after vaccination for any/all doses administered to children aged 6 months through 4 years. We concluded that the vaccine is unlikely to induce a heightened risk of SFS.     

Safety and immunogenicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: beginning of epidemic control

As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage.     

Progress towards eliminating Hib in Australia: an evaluation of Haemophilus influenzae type b prevention in Australia, 1 July 1993 to 30 June 2000.

The status of Haemophilus influenzae (Hib) disease and its prevention by vaccination was reviewed for the period 1997 to 2000. This forms the background to a change in national vaccine policy, from the use of two Hib vaccines to the use of PRP-OMP only throughout Australia from May 2000. Notifications of Hib in the 7-year period between 1993 and 2000 declined by 87 per cent among children 0-4 years of age; adjustment for likely under-reporting increase this to a 95 per cent reduction. Among age groups not included in the immunisation program, there was also a substantial decline in notified cases. Overall, a minimum 430 cases and 13 deaths were prevented by Hib immunisation annually in Australia. Enhanced Hib surveillance recorded 532 cases over seven years, with 353 in unvaccinated persons, 74 fulfilling criteria for true vaccine failure and 75 partially immunised. Of unvaccinated cases, 60 and 182 were eligible for routine and catch-up immunisation respectively. Although the overall incidence for 0-4 years of age declined from 15 to 1.2 cases per 100,000 population, the proportion of cases under six months of age increased from 11 per cent to 23 per cent. Overall vaccine effectiveness, estimated using data from the last five years of the program, was 83 per cent (95% CI 71-91%), increasing to 90 per cent (95% CI 83-94%) when adjusted for under-reporting to the Australian Childhood Immunisation Register. Among Aboriginal and Torres Strait Islander people, the incidence of invasive Hib disease fell from 4.6 cases per 100,000 population to 0.7 cases per 100,000 population but the proportion of cases now occurring among Aboriginal or Torres Strait Islander people increased significantly, from 7 to 15 per cent. The Hib immunisation program in Australia has been highly successful. Nevertheless, experience in Australia and elsewhere indicates that continued careful monitoring of Hib disease, with high quality laboratory surveillance, remains important.     

A prospective study of the effectiveness of the New Zealand meningococcal B vaccine

The effectiveness of a new group B strain-specific meningococcal vaccine referred to as "MeNZB," developed by Chiron Vaccines (Siena, Italy) in collaboration with the Norwegian Institute of Public Health, was assessed in a prospective observational study following a nationwide vaccination program in New Zealand. The vaccination program began in July 2004, and the study uses data from January 2001 to June 2006. A generalized estimating equation model was used to estimate vaccine effectiveness that included potential confounding variables, such as disease progression over time, age, ethnicity, socioeconomic status, seasonality, and geographic region. The model provides strong statistical evidence for a vaccine effect (p < 0.0001), with estimated disease rates 3.7 times higher in the unvaccinated group than in the vaccinated group (95% confidence interval: 2.1, 6.8) and a vaccine effectiveness of 73% (95% confidence interval: 52, 85). An estimated 54 epidemic strain meningococcal cases were prevented in the 2 years since the vaccination program began (95% confidence interval assuming a fixed population size: 22, 115). In a sensitivity analysis, these estimates proved to be robust to modeling assumptions, including population estimates, estimates of the numbers vaccinated, effects of partial vaccination, and temporal autocorrelation.     

Combined administration of serogroup B meningococcal vaccine and conjugated serogroup C meningococcal vaccine is safe and immunogenic in college students

This study evaluated the first use of a combination of the lyophilized components of the conjugated group C vaccine Menjugate reconstituted with the liquid group B outer membrane vesicle (OMV) vaccine MeNZB. At 6-week intervals, healthy residential students received three doses of MeNZB alone or concomitantly with one dose of Menjugate (MeNZB+MenC). Short-lasting injection-site reactions of mild or moderate intensity were frequent in both groups. There were no vaccine-related serious adverse events. After three doses, the percentage of subjects with serum bactericidal assay (SBA) titres > or = 1:8 against the serogroup B strain NZ98/254 was 82% for MeNZB+MenC and 78% for MeNZB. All subjects in the MeNZB+MenC group achieved SBA titres > or = 1:8 against serogroup strain C11 and 67% in the MeNZB group. All SBA and ELISA responses of the combined vaccine were at least as good as for MeNZB alone. After vaccination, the pharyngeal carriage rate of any meningococcus in the vaccinated group had declined from 40% to 21%.     

New Zealand's epidemic of meningococcal disease described using molecular analysis: implications for vaccine delivery

New Zealand's epidemic of meningococcal disease began in mid 1991. Surveillance of meningococcal disease in New Zealand is based on a combination of disease notification and organism characterisation. Case numbers and population rates rose from 53 (1.5 per 100,000 population) in 1990 to a high of 650 (17.4 per 100,000 population) in 2001. The highest rates of disease occur in Pacific peoples under 20 years but the highest percentages of cases occur in Maori and European New Zealanders. The epidemic has been driven by a strain identified as B:4:P1.7b,4, ST-41/44 complex/Lineage III. The stability of the P1.7b,4 Por A protein has been demonstrated suggesting that the epidemic may be controlled by a strain-specific OMV vaccine.     

Cost effectiveness of rotavirus vaccination in Australia

OBJECTIVE: Rotavirus gastroenteritis causes substantial morbidity, including hospital admission, in young children. In the context of recent vaccine developments, this study aimed to estimate the cost-effectiveness of a rotavirus vaccination program in Australia. METHOD: Standard methods of health economic evaluation were used to assess the total cost of rotavirus immunisation (as the difference between estimated vaccination program costs and the cost of disease that would be avoided by immunisation) and relate this to the number of cases of disease that would be prevented. Estimates were made from both societal and health care systems perspectives. RESULTS: Based on Australian data on disease incidence and cost of hospitalisation, the current annual cost of rotavirus disease is about $26.0 million. Using conservative vaccine efficacy estimates, current immunization uptake rates and a cost of $30 per dose of vaccine, rotavirus immunisation would incur a net societal cost of $2.9 million ($11 per child), at a gross program cost of $21.6 million. These estimates are sensitive to two sources of uncertainty in the estimation of program delivery costs: vaccine price and whether separate immunization visits would be required. CONCLUSION: A rotavirus immunisation program would be cost-neutral to Australian society at a vaccine price of $26 per dose (or $19 when health care system costs only are considered). IMPLICATIONS: Rotavirus immunization may be cost-effective in Australia, but considerable uncertainty remains. Policy decisions will depend heavily on pricing of the vaccine and may also need to consider intangible costs not accounted for in this analysis.     

Measuring disparities in immunisation coverage among children in New Zealand

For the past 20 years, New Zealand has experienced low immunisation coverage levels. Following the introduction of the National Immunisation Register (NIR) in 2005 many practitioners envisaged improved overall immunisation uptake through enhanced surveillance and monitoring capacities. This study aimed to investigate the geographical distribution and variables associated with disparities in immunisation uptake in New Zealand using a large NIR data set of children aged 12 months old in 2007–2009. DHB immunisation uptake was adjusted for individual ethnicity and deprivation status, year of birth and geographic location. Substantial variations in uptake by ethnicity and District Health Board (DHB) level were evident. Māori (NZ indigenous) and ‘Other’ ethnicity remain a substantial risk factor for low immunisation uptake after controlling for socio-economic deprivation. In addition, a general north–south gradient was confirmed across New Zealand. Current immunisation programme strategies for planners and providers in New Zealand need to recognise varying DHB compositions in order to provide efficient service provision and to focus on those groups at higher risk of not being immunised.     

Family physician perspectives on barriers to childhood immunisation

New Zealand (NZ) has inadequate vaccine coverage and associated disease outbreaks. International research illustrates the importance of provider behaviour in improving vaccine uptake. To understand the immunisation knowledge, views, concerns and educational needs of NZ family physicians, qualitative and quantitative national data was gathered from randomised telephone surveys. Response rate was 60% with respondents' characteristics closely matched to key demographics of NZ family physicians. The most significant barrier to improving immunisation rates identified was parental concern over vaccine safety and associated misconceptions. The second major barrier identified was lack of funding to health providers. A clear need for improvement in family physician knowledge of contraindications to vaccines was highlighted. Family physicians expressed a need for better resources to more effectively address parental fears and misconceptions. Strategies to address these issues include an increased focus on family physician educational needs, extra resources to assist with more effective communication to parents and a review of the present funding of providers for immunisation services.     

Cost-effectiveness analysis of switching from a trivalent to a quadrivalent inactivated influenza vaccine in the Peruvian immunisation programme

BackgroundSeasonal influenza is an acute respiratory infection mostly caused by type A and B influenza viruses. The severe form of the infection can be life-threatening and lead to a significant burden. Vaccination is the most efficient way of preventing influenza infections and limit this burden.ObjectivesTo assess the cost-effectiveness of switching from a trivalent influenza vaccine (TIV) to a quadrivalent influenza vaccine (QIV) in the vaccination programme in Peru, and to evaluate the health and economic impact of reaching the vaccination coverage rate targeted by the Ministry of Health.MethodsA decision-analytic static cost-effectiveness model, was adapted to the Peruvian setting under both payer and societal perspectives.ResultsA switch from TIV to QIV would prevent 29,126 additional cases (including 12,815 consultations), 54 hospitalisations, and 23 deaths related to influenza, mostly in the population <2 years-old and >60 years-old. This would lead to a saving of US $505,206 under the payer perspective, that would partially offset the investment necessary to introduce QIV into the immunisation programme. The resulting incremental cost-effectiveness ratio (ICER) is $16,649 per QALYs gained. The main drivers of the model results were vaccine efficacy against influenza B viruses, degree of match, vaccines prices and proportion of cases attributable to influenza B. The robustness of the results seems satisfactory as QIV has the probability of being a cost-effective strategy of 83.8% (considering a threshold of three GDP per capita). Reaching the coverage targeted by the Ministry of Health would result in health benefits and disease management savings, and lower ICERs.ConclusionIntroducing QIV instead of TIV in the Peruvian immunisation programme is expected to be a cost-effective strategy, especially in younger children and the elderly. The benefit of QIV would be even more important if the coverage targeted by the Ministry of Health would be reached in the most vulnerable groups.     

First year experience of rotavirus immunisation programme in Finland

Introduction

This study aimed to estimate the impact of rotavirus (RV) immunisation programme on the total hospital treated acute gastroenteritis (AGE) burden, as well as, on severe RV disease burden in Finland during the first year after immunisation programme introduction. Such studies can also be considered as a vaccine-probe-study, where unspecific disease burden prevented by immunisation is assumed to be caused by the agent the vaccine is targeted against.

Methods

The RV related outcome definitions were based on data registered in the National Hospital Discharge Register coded using ICD 10 codes. Incidences of hospitalised and hospital outpatient cases of AGE and RVGE were compared prior (1999–2005) and after (2010) the start of the programme among children under 5 years of age. ICD 10 codes utilised were A00-A09, R11 and K52.

Results

The reductions in disease burden, when the post-introduction year was compared to pre-vaccine era, were 80.3% (95% CI 74.5–84.7) in hospital inpatient RVGE among toddlers less than 1 year of age and 53.9% (95% CI 49.8–57.7) when the total inpatient AGE burden was considered in the same age group. For the corresponding hospital outpatient cases the reductions were 78.8% (95% CI 48.4–91.3) and 12.5% (7.1–17.7). The overall vaccine impact against confirmed RVGE in age cohorts eligible for vaccination before the RV season 2010 was 97% (95% CI 90.7–99.0). If the total reductions, both in diagnosed RVGE, as well as in cases without definite microbial diagnosis, were expected to be RVGE, population based estimates for the total disease burden can be obtained: for inpatient RVGE in children less than 1 year of age the estimate is 10.5/1000 pyrs, while the diagnosed specific incidence was less than half of that, 4.9/1000 pyrs.

Discussion

During the first post-vaccination year 2010, RV immunisation programme clearly managed to control the severe, hospital treated, forms of RVGE. The total disease burden is a more valuable end point than mere diagnosed cases as laboratory confirmation practises change after vaccine introduction. Our study is limited by the very short post-introduction follow up.     

Cost-benefit analyses of supplementary measles immunisation in the highly immunized population of New Zealand

As endemic measles is eliminated from countries through increased immunisation, the economic benefits of enhanced immunisation programs may come into question. New Zealand has suffered from outbreaks after measles introductions from abroad and we use it as a model system to understand the benefits of catch up immunisation in highly immunised populations. We provide cost-benefit analyses for measles supplementary immunisation in New Zealand. We model outbreaks based on estimates of the basic reproduction number in the vaccinated population (R_v, the number of secondary infections in a partially immunised population), based on the number of immunologically-naïve people at district and national levels, considering both pre- and post-catch up vaccination scenarios. Our analyses suggest that measles R_v often includes or exceeds one (0.18–3.92) despite high levels of population immunity. We calculate the cost of the first 187 confirmed and probable measles cases in 2014 to be over NZ$1 million (∼US$864,200) due to earnings lost, case management and hospitalization costs. The benefit-cost ratio analyses suggest additional vaccination beyond routine childhood immunisation is economically efficient. Supplemental vaccination-related costs are required to exceed approximately US$66 to US$1877 per person, depending on different scenarios, before supplemental vaccination is economically inefficient. Thus, our analysis suggests additional immunisation beyond childhood programs to target naïve individuals is economically beneficial even when childhood immunisation rates are high.