Risk Factors and Attack Rates of Seasonal Influenza Infection: Results of the Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) Seroepidemiologic Cohort Study.

Background: Understanding the attack rate of influenza infection and the proportion who become ill by risk group is key to implementing prevention measures. While population-based studies of antihemagglutinin antibody responses have been described previously, studies examining both antihemagglutinin and antineuraminidase antibodies are lacking. Methods: In 2015, we conducted a seroepidemiologic cohort study of individuals randomly selected from a population in New Zealand. We tested paired sera for hemagglutination inhibition (HAI) or neuraminidase inhibition (NAI) titers for seroconversion. We followed participants weekly and performed influenza polymerase chain reaction (PCR) for those reporting influenza-like illness (ILI). Results: Influenza infection (either HAI or NAI seroconversion) was found in 321 (35% [95% confidence interval, 32%-38%]) of 911 unvaccinated participants, of whom 100 (31%) seroconverted to NAI alone. Young children and Pacific peoples experienced the highest influenza infection attack rates, but overall only a quarter of all infected reported influenza PCR-confirmed ILI, and one-quarter of these sought medical attention. Seroconversion to NAI alone was higher among children aged <5 years vs those aged ≥5 years (14% vs 4%; P < .001) and among those with influenza B vs A(H3N2) virus infections (7% vs 0.3%; P < .001). Conclusions: Measurement of antineuraminidase antibodies in addition to antihemagglutinin antibodies may be important in capturing the true influenza infection rates.

Developing the design of a continuous national health survey for New Zealand.

BACKGROUND: A continuously operating survey can yield advantages in survey management, field operations, and the provision of timely information for policymakers and researchers. We describe the key features of the sample design of the New Zealand (NZ) Health Survey, which has been conducted on a continuous basis since mid-2011, and compare to a number of other national population health surveys. METHODS: A number of strategies to improve the NZ Health Survey are described: implementation of a targeted dual-frame sample design for better Maori, Pacific, and Asian statistics; movement from periodic to continuous operation; use of core questions with rotating topic modules to improve flexibility in survey content; and opportunities for ongoing improvements and efficiencies, including linkage to administrative datasets. RESULTS AND DISCUSSION: The use of disproportionate area sampling and a dual frame design resulted in reductions of approximately 19%, 26%, and 4% to variances of Maori, Pacific and Asian statistics respectively, but at the cost of a 17% increase to all-ethnicity variances. These were broadly in line with the survey's priorities. Respondents provided a high degree of cooperation in the first year, with an adult response rate of 79% and consent rates for data linkage above 90%. CONCLUSIONS: A combination of strategies tailored to local conditions gives the best results for national health surveys. In the NZ context, data from the NZ Census of Population and Dwellings and the Electoral Roll can be used to improve the sample design. A continuously operating survey provides both administrative and statistical advantages.

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.

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.

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.

Surveillance of vaccine breakthrough cases following MeNZB vaccination.

AIM: To describe and investigate epidemic strain serogroup B meningococcal disease in recipients of the meningococcal vaccine, MeNZB. METHOD: Epidemic strain meningococcal disease cases in vaccine recipients were identified by matching disease notification and laboratory data against the National Immunisation Register. Descriptive analyses were undertaken for disease cases aged under 20 years and vaccine breakthrough cases (epidemic strain meningococcal disease cases with onset 28 or more days after receipt of the third MeNZB dose). Questionnaires were sent to hospital clinicians requesting medical histories and laboratory test results for vaccine breakthrough cases. A committee reviewed this information to assess immune competence in these cases. RESULTS: From the start of the meningococcal B immunisation programme in July 2004 to the end of 2006, 34 vaccine breakthrough cases were identified. No underlying host factors were identified that explained disease occurrence for the 30 cases (88.2%) for whom questionnaires were completed. For 12 (35.3%) cases all requested laboratory tests to assess immune competence were performed and these subjects were judged to be immune competent. CONCLUSION: While epidemic strain meningococcal disease incidence has fallen dramatically with the introduction of the vaccine, these early results confirm the expectation that vaccine breakthrough cases will occur in immune competent individuals given the anticipated vaccine effectiveness of approximately 75%.

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.

The Intensive Vaccines Monitoring Programme (IVMP): an electronic system to monitor vaccine safety in New Zealand.

New Zealand introduced a tailor-made vaccine (MeNZB) for epidemic control of Group B meningococcal disease. The Intensives Vaccine Monitoring Programme (IVMP), which prospectively collected data electronically on a cohort of children receiving vaccinations in sentinel practices across NZ, was developed as part of a national multi-faceted safety strategy. The main aim of the IVMP was to identify the presence of unexpected adverse events occurring with MeNZB vaccination. We describe the methodology and success factors plus consider the limitations encountered in this system which shows potential as a means for post-marketing vaccine and medicine surveillance in the future.

The risk of bronchiolitis hospitalisation following administration of a group B meningococcal vaccine in New Zealand.

AIM: During the Phase II clinical trials for a new group B meningococcal vaccine in New Zealand, six study participants (including five children who had been vaccinated with this vaccine) were hospitalised due to acute bronchiolitis. We examined more closely the potential association between bronchiolitis hospitalisation and this vaccine. METHODS: We used descriptive comparisons, a cohort analysis, and a matched case-control study to examine the potential association of bronchiolitis hospitalisation with the vaccine using New Zealand Health Information Service hospital discharge data and vaccination data from the National Immunisation Register. RESULTS: The distribution of hospitalised bronchiolitis cases throughout New Zealand immediately following the introduction of the vaccine was consistent with historical (pre-vaccine) patterns. Similarly, all point estimates for relative risk (cohort analysis) and odds ratio (case-control study) for assessing the potential association between bronchiolitis hospitalisation and the vaccine were less than 1.00. CONCLUSIONS: We concluded that this vaccine is not associated with an increased risk of hospitalisation for bronchiolitis.

Post-marketing safety monitoring of a new group B meningococcal vaccine in New Zealand, 2004-2006.

New Zealand introduced a new outer membrane vesicle vaccine in 2004 to combat an epidemic of group B meningococcal disease. An Independent Safety Monitoring Board oversaw intensive safety monitoring, which included hospital surveillance, health professional reporting (passive and active) and mortality monitoring. With over three million doses administered to individuals aged under 20 years, the monitoring results provide consistent evidence supporting the vaccine's safety.

Prevalence and risk factors for Chlamydia trachomatis infection in female New Zealand university students.

AIMS: To measure the prevalence of urogenital Chlamydia trachomatis infection in a sample of sexually active female university students, to identify risk factors associated with infection, and to measure the uptake of screening. METHODS: Female students aged 18-25 years, presenting to a university student health service from March to October 2003, were invited to participate. Information on demographic details and sexual behaviour was collected with a self-completed questionnaire. The students were tested for Chlamydia infection using the Roche Amplicor CT/NG PCR test of first void urine specimens. RESULTS: Chlamydia prevalence was 2.7% (19/715). Infection was associated with previous sexually transmitted infection (STI), non-European ethnicity, and irregular use of condoms. Most participants were not using condoms regularly despite the risk of STI. Screening was technically straightforward and the participation rate was 59.9% (718/1199). CONCLUSIONS: New Zealand needs to develop and implement an adequately resourced and evidence-based Chlamydia control strategy. This strategy should contain national guidelines on screening in a range of settings, including universities, as well as strategies for primary prevention of Chlamydia and other STI. Clinicians treating university-aged students should consider opportunistic Chlamydia screening for all of those who are sexually active. Further research, preferably in conjunction with intervention studies, is essential to assess the prevalence of Chlamydia in other populations.