Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Rheumatic fever recurrences in New Zealand 2010-14.

AIM: To describe the epidemiology and clinical characteristics of recurrences of acute rheumatic fever (ARF) in New Zealand 2010-14. METHOD: Retrospective hospital chart review for ARF with repeat hospital admissions from 2010-14, to identify recurrences of ARF. Definitions of recurrence as per NZ Heart Foundation Guidelines. RESULTS: There were 65 episodes of recurrent ARF among 60 patients. Maori 51%, Pacific 49%. Arthritis and carditis were the most common major manifestations. Median age at recurrence 21.6 years, (8-42 years), with 83% patients over 15 years. There were 841 first episodes of ARF in New Zealand in 2010-4. Overall New Zealand ARF recurrence rate was 7.2% (CI 5.5-8.9%). The recurrence rate was 4% for those under 16 years, 16% for those aged 16-20 and 25% for those >20 years (p<0.05). Seventy-three percent of recurrences occurred in the Auckland region. Recurrences of ARF were strongly associated with RHD progression. CONCLUSION: The risk of recurrence of ARF in New Zealand is low for children. In contrast, recurrences of ARF in New Zealand occur predominantly after age 15, and disproportionately in the Auckland DHBs. Current medical systems and registers may not be meeting the needs of adolescents and adults requiring secondary prophylaxis.

Streptococcal Serology in Acute Rheumatic Fever Patients: Findings From 2 High-income, High-burden Settings.

BACKGROUND: Globally, there is wide variation in streptococcal titer upper limits of normal (ULN) for antistreptolysin O (ASO) and anti-deoxyribonuclease B (ADB) used as an evidence of recent group A streptococcal infection to diagnose acute rheumatic fever (ARF). METHODS: We audited ASO and ADB titers among individuals with ARF in New Zealand (NZ) and in Australia's Northern Territory. We summarized streptococcal titers by different ARF clinical manifestations, assessed application of locally recommended serology guidelines where NZ uses high ULN cut-offs and calculated the proportion of cases fulfilling alternative serologic diagnostic criteria. RESULTS: From January 2013 to December 2015, group A streptococcal serology results were available for 350 patients diagnosed with ARF in NZ and 182 patients in Northern Territory. Median peak streptococcal titers were similar in both settings. Among NZ cases, 267/350 (76.3%) met NZ serologic diagnostic criteria, whereas 329/350 (94.0%) met Australian criteria. By applying Australian ULN titer cut-off criteria to NZ cases, excluding chorea, ARF definite cases would increase by 17.6% representing 47 cases. CONCLUSIONS: ASO and ADB values were similar in these settings. Use of high ULN cut-offs potentially undercounts definite and probable ARF diagnoses. We recommend NZ and other high-burden settings to use globally accepted, age-specific, lower serologic cut-offs to avoid misclassification of ARF.

Primary prevention of rheumatic fever in the 21st century: evaluation of a national programme.

Background: Acute rheumatic fever (ARF) has largely disappeared from high-income countries. However, in New Zealand (NZ) rates remain high in indigenous (Maori) and Pacific populations. In 2011, NZ launched an intensive and unparalleled primary Rheumatic Fever Prevention Programme (RFPP). We evaluated the impact of the school-based sore throat service component of the RFPP. Methods: The evaluation used national trends of all-age first episode ARF hospitalisation rates before (2009-11) and after (2012-16) implementation of the RFPP. A retrospective cohort study compared first-episode ARF incidence during time-not-exposed (23 093 207 person-days) and time-exposed (68 465 350 person-days) with a school-based sore throat service among children aged 5-12 years from 2012 to 2016. Results: Following implementation of the RFPP, the national ARF incidence rate declined by 28% from 4.0 per 100 000 [95% confidence interval (CI) 3.5-4.6] at baseline (2009-11) to 2.9 per 100 000 by 2016 (95% CI 2.4-3.4, P <0.01). The school-based sore throat service effectiveness overall was 23% [95% CI -6%-44%; rate ratio (RR) 0.77, 95% CI 0.56-1.06]. Effectiveness was greater in one high-risk region with high coverage (46%, 95% CI 16%-66%; RR 0.54, 95% CI 0.34-0.84). Conclusions: Population-based primary prevention of ARF through sore throat management may be effective in well-resourced settings like NZ where high-risk populations are geographically concentrated. Where high-risk populations are dispersed, a school-based primary prevention approach appears ineffective and is expensive.

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.

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.

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.

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 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.

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.