The combined impact of implementing HPV immunisation and primary HPV screening in New Zealand: Transitional and long-term benefits, costs and resource utilisation implications.

BACKGROUND: In response to emergent evidence, many countries are transitioning from cytology-based to HPV screening. We evaluated the impact of an upcoming transition on health outcomes and resource utilisation in New Zealand. METHODS: An extensively validated model of HPV transmission, vaccination, natural history and cervical screening ('Policy1-Cervix') was utilised to simulate a transition from three-yearly cytology for women 20-69 years to five-yearly HPV screening with 16/18 genotyping for women 25-69 years, accounting for population growth and the impact of HPV immunisation. Cervical cancer rates, resources use (test volumes), costs, and test positivity rates from 2015 to 2035 were estimated. FINDINGS: By 2035, the transition to HPV screening will result in declines in cervical cancer incidence and mortality rates by 32% and 25%, respectively, compared to 2018. A potentially detectable 5% increase in cervical cancer incidence due to earlier detection is predicted for the year of transition. Annual numbers of women screened will fluctuate with the five-year screening interval. Cytology volumes will reduce by over 80% but colposcopy volumes will be similar to pre-transition rates, and program costs will be reduced by 16%. A 9% HPV test positivity rate is expected in the first round of HPV screening (2019-2023), with 2.7% of women referred for colposcopy. Transitioning from cytology to primary HPV cervical screening could avert 149 cancer cases and 45 deaths by 2035. CONCLUSION: Primary HPV screening and vaccination will reduce cervical cancer and resources use. A small transient apparent increase of invasive cancer rates due to earlier detection may be detectable at the population level, reflecting the introduction of a more sensitive screening test. These findings can be used to inform health services planning and public communications surrounding program implementation.

Half a Century of Wilson & Jungner: Reflections on the Governance of Population Screening.

Background: In their landmark report on the "Principles and Practice of Screening for Disease" (1968), Wilson and Jungner noted that the practice of screening is just as important for securing beneficial outcomes and avoiding harms as the formulation of principles. Many jurisdictions have since established various kinds of "screening governance organizations" to provide oversight of screening practice. Yet to date there has been relatively little reflection on the nature and organization of screening governance itself, or on how different governance arrangements affect the way screening is implemented and perceived and the balance of benefits and harms it delivers. Methods: An international expert policy workshop convened by Sturdy, Miller and Hogarth. Results: While effective governance is essential to promote beneficial screening practices and avoid attendant harms, screening governance organizations face enduring challenges. These challenges are social and ethical as much as technical. Evidence-based adjudication of the benefits and harms of population screening must take account of factors that inform the production and interpretation of evidence, including the divergent professional, financial and personal commitments of stakeholders. Similarly, when planning and overseeing organized screening programs, screening governance organizations must persuade or compel multiple stakeholders to work together to a common end. Screening governance organizations in different jurisdictions vary widely in how they are constituted, how they relate to other interested organizations and actors, and what powers and authority they wield. Yet we know little about how these differences affect the way screening is implemented, and with what consequences. Conclusions: Systematic research into how screening governance is organized in different jurisdictions would facilitate policy learning to address enduring challenges. Even without such research, informal exchange and sharing of experiences between screening governance organizations can deliver invaluable insights into the social as well as the technical aspects of governance.

Immunogenicity and tolerability in infants of a New Zealand epidemic strain meningococcal B outer membrane vesicle vaccine.

BACKGROUND: An outer membrane vesicle meningococcal vaccine (MeNZB), was developed for the New Zealand epidemic strain of Neisseria meningitidis B:4:P1.7-2,4. METHODS: A phase II, randomized, observer blind, controlled study evaluating the safety, reactogenicity, and immunogenicity of MeNZB administered with routine New Zealand immunizations at 6 weeks, 3 months, and 5 months of age (n = 375). Group 1 (n = 250) received 25 mug MeNZB and routine immunizations with a fourth MeNZB dose given at 10 months (n = 51). Group 2 (n = 125) received routine immunizations only. Sero-response was a > or =4-fold rise in vaccine strain serum bactericidal antibody titer compared with baseline or a titer of at least 1:8 for baselines <1:4. Reactogenicity was monitored for 7 days after vaccination. RESULTS: Sero-response in Group 1 was achieved in 53% (95% Confidence interval [CI]: 46-59, n = 239) and 69% (95% CI: 54-80, n = 45) with geometric mean antibody titers of 9 (95% CI: 7-10) and 22 (95% CI: 12-39) after the third and fourth doses, respectively. No negative interference by MeNZB on routine immunizations was detected. There were no serious adverse events judged to be vaccine related. CONCLUSIONS: In this group of New Zealand infants, 4 MeNZB doses were required to demonstrate titers comparable with those achieved after 3 doses in older children. MeNZB was safe when used concomitantly with routine New Zealand immunizations to 5 months of age.

New zealand epidemic strain meningococcal B outer membrane vesicle vaccine in children aged 16-24 months.

BACKGROUND: New Zealand has experienced an epidemic of Neisseria meningitidis dominated by strain B:4:P1.7b,4 since 1991. Children younger than 5 years are at highest risk. Previous serogroup B outer membrane vesicle (OMV) strain specific vaccines have shown variable efficacy in this age group. OBJECTIVE: To evaluate the immunogenicity, reactogenicity and safety in 16-24-month-old children of an OMV vaccine developed against the New Zealand epidemic strain. METHODS: Children (332) aged 16-24 months were randomized to receive the New Zealand candidate vaccine made using strain NZ98/254 (B:4:P1.7b,4) or the Norwegian parent vaccine made using strain 44/76 (B:15:P1.7,16). Vaccines (25 microg/dose) were administered at 0, 6 and 12 weeks in this observer-blind trial. Immune response was measured by serum bactericidal assay and enzyme-linked immunosorbent assay. Sero-response was defined as a 4-fold or greater rise in serum bactericidal antibody titer compared with baseline, with titers <1:4 required to increase to >or=1:8 to be considered a sero-response. Local and systemic reactions were monitored for 7 days after vaccination. RESULTS: Sero-response against NZ98/254 was achieved after 3 doses in 75% (95% CI: 69-80%) receiving the New Zealand candidate vaccine by both intention to treat (ITT) and per protocol (PP) analyses. In Norwegian parent vaccinees this was seen in 3% (0-12%) (ITT) and 4% (0-13%) (PP). Vaccines were well tolerated with no vaccine-related serious adverse events. CONCLUSION: The New Zealand candidate vaccine administered to these 16-24-month-old children in 3 doses was safe and elicited a promising immune response against the candidate vaccine strain NZ98/254 (N. meningitidis B:4:P1.7b,4) contributing to vaccine licensure for this age group.

The strategy to control New Zealand's epidemic of group B meningococcal disease.

BACKGROUND: In New Zealand today, babies of Pacific ethnicity born in South Auckland have a 1-in-48 chance of contracting meningococcal disease by the time they are 5 years of age. METHODS: The New Zealand government, Chiron Vaccines and the University of Auckland have collaborated to develop and investigate a group B meningococcal vaccine to allow a mass-immunization program to control a prolonged and intense epidemic. Within 3 years, a strain-specific meningococcal outer membrane vesicle vaccine has been developed, and overlapping clinical trials have been undertaken; a report was submitted for regulatory approval within 2 years. An important aspect of the project's strategy was to apply, with physicochemical data, the results of the New Zealand outer membrane vesicle vaccine trials to the parent vaccine produced and evaluated by the Norwegian National Institute of Public Health. Immunogenicity results for the New Zealand vaccine are promising, with the vaccine showing a reactogenicity profile similar to that of the parent vaccine. CONCLUSIONS: Controlling the epidemic depends on delivering an effective vaccine to the individuals at greatest risk, ie, mainly Maori and Pacific populations that previous health programs have struggled to reach. Participation of and partnership with these communities in public health decision-making and vaccine delivery will be critical to a successful immunization program.

Vaccines against meningococcal serogroup B disease containing outer membrane vesicles (OMV): lessons from past programs and implications for the future.

The utility of wild-type outer membrane vesicle (wtOMV) vaccines against serogroup B (MenB) meningococcal disease has been explored since the 1970s. Public health interventions in Cuba, Norway and New Zealand have demonstrated that these protein-based vaccines can prevent MenB disease. Data from large clinical studies and retrospective statistical analyses in New Zealand give effectiveness estimates of at least 70%. A consistent pattern of moderately reactogenic and safe vaccines has been seen with the use of approximately 60 million doses of three different wtOMV vaccine formulations. The key limitation of conventional wtOMV vaccines is their lack of broad protective activity against the large diversity of MenB strains circulating globally. The public health intervention in New Zealand (between 2004-2008) when MeNZB was used to control a clonal MenB epidemic, provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness estimates and communication to the public. The experience with wtOMV vaccines also provide important information for the next generation of MenB vaccines designed to give more comprehensive protection against multiple strains.

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.

Health policy responses to rising rates of multi-morbid chronic illness in Australia and New Zealand.

OBJECTIVE: To examine current health policy in Australia and New Zealand and assess the extent to which the policies equip these countries to meet the challenges associated with increasing rates of multi-morbid chronic illnesses. METHOD: We examined reports from agencies holding data relating to chronic illness in both countries, looking at prevalence trends and the frequency of multiple morbidities being recorded. We undertook content analysis of health policy documents from Australian and New Zealand government agencies. RESULTS: The majority of people with chronic illness have multiple morbidities. Multi-morbid chronic illnesses significantly effect the health of people in both Australia and New Zealand and place substantial demands on the health systems of those countries. These consequences are both predicted to increase dramatically in the near future. Despite this, neither country explicitly acknowledges multi-morbidity as a major factor in their policies addressing chronic illness. CONCLUSION AND IMPLICATION: In addition to considering policy responses to chronic illness, policy makers should explicitly consider policies shaped to address the needs of people with multi-morbid chronic illness.

Delivering a safe and effective strain-specific vaccine to control an epidemic of group B meningococcal disease.

In response to a devastating group B meningococcal disease epidemic in New Zealand, a case was prepared for new health funding and a new outer membrane vesicle vaccine, MeNZB, developed. Following clinical trials demonstrating satisfactory immunogenicity and safety profiles a national implementation strategy was prepared. MeNZB was introduced halfway through the 14th year of the epidemic with a campaign targeting children and young people aged under 20 years delivered over 2 years. By its completion in June 2006, the vaccine had been delivered to more than 1 million young people. All of the above steps were achieved within 5 years. This unique endeavour was possible due to a private/public partnership between the New Zealand Ministry of Health and Chiron Vaccines. This paper summarises the outcomes of this campaign including coverage levels achieved, evidence of vaccine effectiveness and safety, and the strategies used to manage key events and risks that emerged during the campaign.

Use of an observational cohort study to estimate the effectiveness of the New Zealand group B meningococcal vaccine in children aged under 5 years.

BACKGROUND: In July 2004 a strain-specific vaccine was introduced to combat an epidemic of group B meningococcal disease in New Zealand. We estimated the effectiveness of this vaccine in pre-school-aged children. METHODS: We conducted a cohort analysis of all children in New Zealand who were aged 6 months to <5 years at the time the vaccine became available for that age group in their area. We defined cases as children who were diagnosed with laboratory-confirmed epidemic strain meningococcal disease. We calculated person-days-at-risk using data from the National Immunization Register and population estimates from Statistics New Zealand. We estimated vaccine effectiveness as 1--relative risk. RESULTS: Compared with unvaccinated children, fully vaccinated children were five to six times less likely to contract epidemic strain meningococcal disease in the 24 months after they became eligible to receive a full vaccination series, corresponding to an estimated vaccine effectiveness of 80.0% (95% confidence interval: 52.5-91.6) for children aged 6 months to <5 years and 84.8% (95% confidence interval: 59.4-94.3) for children aged 6 months to <3 years. CONCLUSIONS: With over 3 million doses administered to individuals aged under 20 years throughout New Zealand, combined evidence from the Phase I and II clinical trials, the descriptive epidemiology of meningococcal disease, and this study provide evidence supporting the effectiveness of this vaccine in the 2 years following vaccination.