Pertussis epidemiology in adults: Retrospective analysis of pertussis incidence and association with comorbidities among adult populations in Aotearoa New Zealand, using national administrative datasets.

BACKGROUND: In New Zealand, approximately half reported pertussis cases are adult. Studies indicate underestimated pertussis burden in this population and probable reservoir for childhood pertussis. Pertussis is linked to chronic obstructive pulmonary disease (COPD) development and increased risk with pre-existing COPD. While acellular pertussis vaccines are available for adults, data on pertussis disease burden in adults and association with COPD remain limited. AIM: To estimate pertussis incidence in New Zealand adult health service user (HSU) population aged ≥ 18 between 2008-2019 and inform adult pertussis vaccination strategies by assessing disease burden and risk factors in different adult populations. METHODS: Retrospective observational cohort study using an HSU cohort, formed by linking administrative health data using unique National Health Index identifier. For primary analysis, annual incidence rates were calculated using pertussis hospitalisations and notifications. In secondary analysis, Cox proportional hazards survival analyses explored association between pertussis in adults and chronic comorbidities. RESULTS: The cohort had 2,907,258 participants in 2008 and grew to 3,513,327 by 2019, with 11,139 pertussis cases reported. Highest annual incidence rate of 84.77 per 100,000 PYRS in 2012, notably affecting females, those aged 30-49 years, and European or Maori ethnicity. Adjusting for sociodemographic variables found no significant risk of prior pertussis notification leading to comorbidity diagnosis (Adjusted-HR: 0.972). However, individuals with prior comorbidity diagnosis had 16 % greater risk of receiving pertussis notification or diagnosis (Adjusted-HR: 1.162). CONCLUSIONS: Study found significant pertussis burden among the HSU adult cohort and highlighted higher risk of pertussis for those with recent comorbidity diagnoses. Vaccination for pertussis should be recommended for individuals with comorbidities to reduce infection risk and disease severity. GPs must have capability to test for pertussis, given it is notifiable disease with implications for individuals, their families, and broader population. High-quality disease surveillance is crucial for informing policy decisions.

Vaccine decision making in New Zealand: a discrete choice experiment.

BACKGROUND: Vaccine hesitancy is a significant threat to global health. A key part of addressing hesitancy is to ensure that public health messaging prioritises information that is considered important to the public. This study aimed to examine how different vaccine characteristics affect public preferences for vaccines in New Zealand, what trade-offs they are willing to make between different vaccine characteristics, and how their preferences are affected by their vaccine-related conspiracy beliefs and COVID-19 vaccination status. METHODS: An online discrete choice experiment (DCE) was designed to elicit individual preferences about vaccines using the 1000minds platform. Members of the general population of New Zealand aged ≥ 18 years were invited to complete the DCE. Participants were asked to indicate their preference between two options showing different combinations of vaccine characteristics. Data on sociodemographic characteristics were collected. Beliefs were measured using the vaccine conspiracy beliefs scale (VCBS) with scores ≥ 19 indicating strong vaccine-related conspiracy beliefs. The DCE was analysed using the PAPRIKA method (Potentially All Pairwise RanKings of all possible Alternatives) and preferences compared between respondents with high versus low VCBS scores and vaccinated versus unvaccinated respondents for COVID-19. RESULTS: A total of 611 respondents from 15 regions completed the DCE. Mean (SD) age was 45.9 (14.7) years with most having had 2 or more doses of the coronavirus vaccine (86%). Mean (SD) VCBS score was 18.5 (12.4) indicating moderate vaccine-related conspiracy beliefs. Risk of severe adverse effects was the most highly valued vaccine characteristic, followed by vaccine effectiveness and duration of protection. Vaccine origin and route of administration were ranked least important. Respondents scoring high on the VCBS placed less value on the effectiveness of vaccines but greater value on development time and total number of doses (p < 0.001). COVID-19 unvaccinated respondents ranked development time and total number of doses more highly than those vaccinated respondents (p < 0.001). CONCLUSIONS: Risk of severe adverse effects, vaccine effectiveness and duration of protection were rated by the New Zealand public as the top three most important vaccine characteristics. This information is important for informing public health messaging to promote vaccine uptake and inform vaccine decision-making.

Changing Mindsets About Side Effects of the COVID-19 Vaccination: A Randomized Controlled Trial.

BACKGROUND: Side-effect concerns are a major barrier to vaccination against COVID-19 and other diseases. Identifying cost- and time-efficient interventions to improve vaccine experience and reduce vaccine hesitancy-without withholding information about side effects-is critical. PURPOSE: Determine whether a brief symptom as positive signals mindset intervention can improve vaccine experience and reduce vaccine hesitancy after the COVID-19 vaccination. METHODS: English-speaking adults (18+) were recruited during the 15-min wait period after receiving their second dose of the Pfizer COVID-19 vaccination and were randomly allocated to the symptom as positive signals mindset condition or the treatment as usual control. Participants in the mindset intervention viewed a 3:43-min video explaining how the body responds to vaccinations and how common side effects such as fatigue, sore arm, and fever are signs that the vaccination is helping the body boost immunity. The control group received standard vaccination center information. RESULTS: Mindset participants (N = 260) versus controls (N = 268) reported significantly less worry about symptoms at day 3 [t(506)=2.60, p=.01, d=0.23], fewer symptoms immediately following the vaccine [t(484)=2.75, p=.006, d=0.24], and increased intentions to vaccinate against viruses like COVID-19 in the future [t(514)=-2.57, p=.01, d=0.22]. No significant differences for side-effect frequency at day 3, coping, or impact. CONCLUSIONS: This study supports the use of a brief video aimed at reframing symptoms as positive signals to reduce worry and increase future vaccine intentions. CLINICAL TRIAL INFORMATION: Australian New Zealand Clinical Trials Registry: ACTRN12621000722897p.

Side-effect concerns are a major barrier to vaccination against COVID-19 and other diseases. Therefore, the purpose of this study was to determine whether a brief symptom as positive signals mindset intervention could improve vaccine experience and reduce vaccine hesitancy after the COVID-19 vaccination. Participants were recruited during the 15-min wait period after receiving their second dose of the Pfizer COVID-19 vaccination and were randomly allocated to a treatment as usual control condition or to a mindset intervention condition which entailed watching a 3:43-min video explaining how the body responds to vaccinations and how common side effects such as fatigue, sore arm, and fever are signs that the vaccination is helping the body boost immunity. Compared with participants in the control condition, participants in the mindset intervention condition reported significantly less worry about symptoms at day 3, fewer symptoms immediately following the vaccine and increased intentions to vaccinate against viruses like COVID-19 in the future. No significant differences emerged for side-effect frequency at day 3, coping, or impact. These finding provide initial support for cost- and time-efficient interventions to improve vaccine experience and reduce vaccine hesitancy without withholding information about side effects.

A retrospective cohort study investigating the comparative effectiveness of pneumococcal vaccines against hospitalisation with otitis media and pneumonia in New Zealand.

BACKGROUND: Since 2008 New Zealand has used three different formulations of pneumococcal vaccines on the national infant schedule, PCV7, PCV10 and PCV13, switching between PCV10 and PCV13 twice in 10 years. We have used New Zealand's linkable, administrative health data to examine the comparative risk of otitis media (OM) and pneumonia hospitalisations among children receiving three different pneumococcal conjugate vaccines (PCV). METHODS: This was a retrospective cohort study using linked administrative data. Outcomes were otitis media, all cause pneumonia and bacterial pneumonia related hospitalisation for children in three cohorts representing periods where PCVs transitioned between PCV7, PCV10, PCV13 and back to PCV10 between 2011 and 2017. Cox's proportional hazard regression was used to provide hazard ratio estimates to compare outcomes for children vaccinated with different vaccine formulations and to adjust for different sub population characteristics. RESULTS: Each observation period, where different vaccine formulations coincided, and therefore comparable with respect to age and the environment, included over fifty-thousand infants and children. PCV10 was associated with a reduced risk for OM compared with PCV7 (Adjusted HR 0.89, 95 %CI 0.82-0.97). There were no significant differences between PCV10 and PCV13 in risk of hospitalisation with either otitis media or all-cause pneumonia amongst the transition 2 cohort. In the 18 -month follow-up, after transition 3, PCV13 was associated with a marginally higher risk of all-cause pneumonia and otitis media compared to PCV10. CONCLUSION: These results should offer reassurance about the equivalence of these pneumococcal vaccines against the broader pneumococcal disease outcomes OM and pneumonia.

Likelihood-based estimation and prediction for a measles outbreak in Samoa.

Prediction of the progression of an infectious disease outbreak is important for planning and coordinating a response. Differential equations are often used to model an epidemic outbreak's behaviour but are challenging to parameterise. Furthermore, these models can suffer from misspecification, which biases predictions and parameter estimates. Stochastic models can help with misspecification but are even more expensive to simulate and perform inference with. Here, we develop an explicitly likelihood-based variation of the generalised profiling method as a tool for prediction and inference under model misspecification. Our approach allows us to carry out identifiability analysis and uncertainty quantification using profile likelihood-based methods without the need for marginalisation. We provide justification for this approach by introducing a new interpretation of the model approximation component as a stochastic constraint. This preserves the rationale for using profiling rather than integration to remove nuisance parameters while also providing a link back to stochastic models. We applied an initial version of this method during an outbreak of measles in Samoa in 2019-2020 and found that it achieved relatively fast, accurate predictions. Here we present the most recent version of our method and its application to this measles outbreak, along with additional validation.

Multi-decade national cohort identifies adverse pregnancy and birth outcomes associated with acute respiratory illness hospitalisations during the influenza season.

BACKGROUND: Despite the World Health Organization (WHO) recommendation that pregnant women be prioritised for seasonal influenza vaccination, coverage in the Western Pacific Region remains low. Our goal was to provide additional data for the Western Pacific Region about the value of maternal influenza vaccination to pregnant women and their families. METHODS: We conducted a 16-year retrospective cohort to evaluate risks associated with influenza-associated maternal acute respiratory infection (ARI) in New Zealand. ARI hospitalisations during the May to September influenza season were identified using select ICD-10-AM primary and secondary discharge codes from chapter J00-J99 (diseases of the respiratory system). Cox proportional hazards models were used to calculate crude and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: We identified 822,391 pregnancies among New Zealand residents between 2003 and 2018; 5095 (0.6%) had ≥1 associated ARI hospitalisation during the influenza season; these pregnancies were at greater risk of preterm birth (aHR 1.50, 95% CI 1.39-1.61) and low birthweight (aHR 1.64, 95% CI 1.51-1.79) than pregnancies without such hospitalisations. We did not find an association between maternal ARI hospitalisation and fetal death (aHR 0.96, 95% CI 0.69-1.34) during the influenza season. Maternal influenza vaccination was associated with reduced risk of preterm birth (aHR 0.79, 95% CI 0.77-0.82), low birthweight (aHR 0.87, 95% CI 0.83-0.90) and fetal death (aHR 0.50%, 95% CI 0.44-0.57). CONCLUSION: In this population-based cohort, being hospitalised for an ARI during the influenza season while pregnant was a risk factor for delivering a preterm or a low birthweight infant and vaccination reduced this risk.

Increasing Uptake of Maternal Pertussis Vaccinations through Funded Administration in Community Pharmacies.

Although maternal pertussis vaccination is recommended, uptake is suboptimal in New Zealand (NZ), despite full funding in general practice and hospitals. We determined whether funding maternal pertussis vaccination in community pharmacy increases its uptake. Pertussis vaccination during pregnancy was compared between non-contiguous, demographically similar regions of NZ. The pertussis vaccine was funded at pharmacies from Nov 2016 in one NZ region (Waikato), but not in comparator regions (Northland, Hawkes Bay). Vaccinations during pregnancy were determined from the National Immunisation Register, general practice and pharmacy claims data, and a maternity database. Comparisons were made using adjusted odds ratios (OR) and 95% confidence intervals (CI) for Nov 2015 to Oct 2016 versus Nov 2016 to Oct 2019. The odds of pregnancy pertussis vaccination increased in the post-intervention versus pre-intervention period with this increase being larger (p = 0.0014) in the intervention (35% versus 21%, OR = 2.07, 95% CI 1.89-2.27) versus the control regions (38% versus 26%, OR = 1.67, 95% CI 1.52-1.84). Coverage was lower for Maori versus non-Maori, but increased more for Maori in the intervention versus control regions (117% versus 38% increase). It was found that funding maternal pertussis vaccination in pharmacy increases uptake, particularly for Maori women. Measures to increase coverage should include reducing barriers to vaccines being offered by non-traditional providers, including pharmacies.

An Observational Study to Assess the Effectiveness of 4CMenB against Meningococcal Disease and Carriage and Gonorrhea in Adolescents in the Northern Territory, Australia-Study Protocol.

Invasive meningococcal disease (IMD) causes significant morbidity and mortality worldwide with serogroup B being the predominant serogroup in Australia and other countries for the past few decades. The licensed 4CMenB vaccine is effective in preventing meningococcal B disease. Emerging evidence suggests that although 4CMenB impact on carriage is limited, it may be effective against gonorrhoea due to genetic similarities between Neisseria meningitidis and Neisseria gonorrhoeae. This study protocol describes an observational study that will assess the effect of the 4CMenB vaccine against meningococcal carriage, IMD and gonorrhoea among adolescents in the Northern Territory (NT). All 14-19-year-olds residing in the NT with no contraindication for 4CMenB vaccine will be eligible to participate in this cohort study. Following consent, two doses of 4CMenB vaccine will be administered two months apart. An oropharyngeal swab will be collected at baseline and 12 months to detect pharyngeal carriage of Neisseria meningitidis by PCR. The main methodological approaches to assess the effect of 4CMenB involve a nested case control analysis and screening method to assess vaccine effectiveness and an Interrupted Time Series regression analysis to assess vaccine impact. Research ethics approvals have been obtained from Menzies and Central Australian Human Research Ethics Committees and the Western Australian Aboriginal Health Ethics Committee. Results will be provided in culturally appropriate formats for NT remote and regional communities and published in international peer reviewed journals. ClinicalTrials.gov Identifier: NCT04398849.

Influences on Pregnant Women's and Health Care Professionals' Behaviour Regarding Maternal Vaccinations: A Qualitative Interview Study.

The uptake of maternal influenza and pertussis vaccinations is often suboptimal. This study explores the factors influencing pregnant women's and health care professionals' (HCPs) behaviour regarding maternal vaccinations (MVs). Pregnant/recently pregnant women, midwives, pharmacists and general practice staff in Waikato, New Zealand, were interviewed. The analysis used the behaviour change wheel model. Interviews of 18 women and 35 HCPs revealed knowledge about MVs varied with knowledge deficiencies hindering the uptake, particularly for influenza vaccination. HCPs, especially midwives, were key in raising women's awareness of MVs. Experience with vaccinating, hospital work (for midwives) and training increased HCPs' knowledge and proactivity about MVs. A "woman's choice" philosophy saw midwives typically encouraging women to seek information and make their own decision. Women's decisions were generally based on knowledge, beliefs, HCPs' emphasis and their perceived risk, with little apparent influence from friends, family, or online or promotional material. General practice's concentration on children's vaccination and minimal antenatal contact limited proactivity with MVs. Busyness and prioritisation appeared to affect HCPs' proactivity. Multi-pronged interventions targeting HCPs and pregnant women and increasing MV access are needed. All HCPs seeing pregnant women should be well-informed about MVs, including how to identify and address women's questions or concerns about MVs to optimise uptake.

Mapping the maternal vaccination journey and influencing factors for Maori women in Aotearoa New Zealand: a qualitative study.

Introduction Uptake of maternal vaccinations (MVs) is suboptimal in Aotearoa New Zealand, particularly for Maori. Aim To describe Maori women's journeys regarding maternal pertussis and influenza vaccinations and explore influences on uptake. Methods Semi-structured interviews were conducted in Waikato, Aotearoa New Zealand, with pregnant or recently pregnant Maori women, and separately with Maori healthcare professionals (HCPs) to understand women's decisions regarding MVs and enablers and barriers to uptake. Results Nine women and nine HCPs were interviewed. Verbal communications from midwives, general practice and pharmacy strongly influenced women's journeys. Women's decisions appeared largely straight-forward, with influences including awareness, knowledge, underlying beliefs and previous MVs. Enablers for MV uptake included HCPs' discussions, pro-vaccination beliefs, and accessibility. Barriers for MV uptake included poverty (and transport), lack of awareness, insufficient knowledge of benefits, late presentation to the midwife and other commitments or challenges in the women's lives affecting prioritisation of the vaccine. Misconceptions, seasonality, and lower HCP emphasis impaired influenza vaccination uptake. Discussion With multiple barriers to accessing MVs, HCPs who see pregnant women are the primary resource to improve awareness, knowledge, and access through korero (discussions) with the woman and, where possible, being able to administer the vaccinations. These HCPs need to be well-informed, aware of likely concerns women may have and how to address them, encourage these discussions and preferably be trusted.

Methodological frontiers in vaccine safety: qualifying available evidence for rare events, use of distributed data networks to monitor vaccine safety issues, and monitoring the safety of pregnancy interventions.

While vaccines are rigorously tested for safety and efficacy in clinical trials, these trials do not include enough subjects to detect rare adverse events, and they generally exclude special populations such as pregnant women. It is therefore necessary to conduct postmarketing vaccine safety assessments using observational data sources. The study of rare events has been enabled in through large linked databases and distributed data networks, in combination with development of case-centred methods. Distributed data networks necessitate common protocols, definitions, data models and analytics and the processes of developing and employing these tools are rapidly evolving. Assessment of vaccine safety in pregnancy is complicated by physiological changes, the challenges of mother-child linkage and the need for long-term infant follow-up. Potential sources of bias including differential access to and utilisation of antenatal care, immortal time bias, seasonal timing of pregnancy and unmeasured determinants of pregnancy outcomes have yet to be fully explored. Available tools for assessment of evidence generated in postmarketing studies may downgrade evidence from observational data and prioritise evidence from randomised controlled trials. However, real-world evidence based on real-world data is increasingly being used for safety assessments, and new tools for evaluating real-world evidence have been developed. The future of vaccine safety surveillance, particularly for rare events and in special populations, comprises the use of big data in single countries as well as in collaborative networks. This move towards the use of real-world data requires continued development of methodologies to generate and assess real world evidence.

Assessing the Safety of COVID-19 Vaccines: A Primer.

Vaccines against COVID-19 are being developed at speeds not previously achieved. With this unprecedented effort comes challenges for post-marketing safety monitoring and challenges for vaccine safety communication. To deploy these new vaccines fast across diverse populations, it is vital that robust pharmacovigilance and active surveillance systems are in place. Not all countries have the capability or resources to undertake adequate surveillance and will rely on data from those who can. The tools exist to assess COVID-19 vaccines as they are deployed such as surveillance systems, administrative data and case definitions for adverse events of special interest. However, stitching these all together and using them effectively requires investment and collaboration. This paper provides a high-level overview of some of the facets of modern vaccine safety assessment and how they are, or can be, applied to COVID-19 vaccines.

Global landscape analysis of no-fault compensation programmes for vaccine injuries: A review and survey of implementing countries.

To update the landscape analysis of vaccine injuries no-fault compensation programmes, we conducted a scoping review and a survey of World Health Organization Member States. We describe the characteristics of existing no-fault compensation systems during 2018 based on six common programme elements. No-fault compensation systems for vaccine injuries have been developed in a few high-income countries for more than 50 years. Twenty-five jurisdictions were identified with no-fault compensation programmes, of which two were recently implemented in a low- and a lower-middle-income country. The no-fault compensation programmes in most jurisdictions are implemented at the central or federal government level and are government funded. Eligibility criteria for vaccine injury compensation vary considerably across the evaluated programmes. Notably, most programmes cover injuries arising from vaccines that are registered in the country and are recommended by authorities for routine use in children, pregnant women, adults (e.g. influenza vaccines) and for special indications. A claim process is initiated once the injured party or their legal representative files for compensation with a special administrative body in most programmes. All no-fault compensation programmes reviewed require standard of proof showing a causal association between vaccination and injury. Once a final decision has been reached, claimants are compensated with either: lump-sums; amounts calculated based on medical care costs and expenses, loss of earnings or earning capacity; or monetary compensation calculated based on pain and suffering, emotional distress, permanent impairment or loss of function; or combination of those. In most jurisdictions, vaccine injury claimants have the right to seek damages either through civil litigation or from a compensation scheme but not both simultaneously. Data from this report provide an empirical basis on which global guidance for implementing such schemes could be developed.

Gonococcal vaccines: Public health value and preferred product characteristics; report of a WHO global stakeholder consultation, January 2019.

Renewed interest in developing vaccines against Neisseria gonorrhoeae has been sparked by the increasing threat of gonococcal antimicrobial resistance (AMR) and growing optimism that gonococcal vaccines are biologically feasible. Evidence suggests serogroup B Neisseria meningitidis vaccines might provide some cross-protection against N. gonorrhoeae, and new gonococcal vaccine candidates based on several approaches are currently in preclinical development. To further stimulate investment and accelerate development of gonococcal vaccines, greater understanding is needed regarding the overall value that gonococcal vaccines might have in addressing public health and societal goals in low-, middle-, and high-income country contexts and how future gonococcal vaccines might be accepted and used, if available. In January 2019, the World Health Organization (WHO) convened a multidisciplinary international group of experts to lay the groundwork for understanding the potential health, economic, and societal value of gonococcal vaccines and their likely acceptance and use, and for developing gonococcal vaccine preferred product characteristics (PPCs). WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper describes the main discussion points and conclusions from the January 2019 meeting of experts. Participants emphasized the need for vaccines to control N. gonorrhoeae infections with the ultimate goals of preventing adverse sexual and reproductive health outcomes (e.g., infertility) and reducing the impact of gonococcal AMR. Meeting participants also discussed important PPC considerations (e.g., vaccine indications, target populations, and potential immunization strategies) and highlighted crucial research and data needs for guiding the value assessment and PPCs for gonococcal vaccines and advancing gonococcal vaccine development.

Inhaled modified angiotensin converting enzyme 2 (ACE2) as a decoy to mitigate SARS-CoV-2 infection.

COVID-19 is a new zoonotic disease caused by the SARS-CoV-2 virus. Since its emergence in Wuhan City, China, the virus has rapidly spread across the globe causing calamitous health, economic and societal consequences. It causes disproportionately severe disease in the elderly and those with co-morbidities, such as hypertension and diabetes. There is currently no proven treatment for COVID-19 and a safe and effective vaccine is at least a year away. The virus gains access to the respiratory epithelium through cell surface angiotensin converting enzyme 2 (ACE2). The receptor binding domain (RBD) of the virus is unlikely to mutate without loss of pathogenicity and thus represents an attractive target for antiviral treatment. Inhaled modified recombinant human ACE2, may bind SARS-CoV-2 and mitigate lung damage. This decoy strategy is unlikely to provoke an adverse immune response and may reduce morbidity and mortality in high-risk groups.

A Qualitative Study of Views and Experiences of Women and Health Care Professionals about Free Maternal Vaccinations Administered at Community Pharmacies.

Background: A policy to extend funding of maternal pregnancy influenza and pertussis vaccinations to community pharmacies could address low pregnancy vaccine uptake. The policy has been implemented in one region in New Zealand. This study explored the views and experiences of women eligible for the vaccines and health care professionals regarding funded maternal vaccinations in pharmacy. Methods: Women in late pregnancy or with an infant, and midwives, pharmacists, and general practice staff were selected purposively and interviewed regarding maternal vaccinations and the new policy, including their awareness and views of the funded vaccinations in pharmacies, and how this policy worked in practice. Enablers and barriers to vaccination by pharmacists were explored. Interviews were transcribed and analysed using a framework approach. Results: Fifty-three interviews were conducted. Most women and health care professionals viewed funded maternal vaccinations in pharmacies positively with respect to increasing awareness and providing delivery options. Many women received messages from pharmacies. Most pharmacies used posters, leaflets and/or verbal explanation to pregnant women to raise awareness of the vaccinations. Not all pharmacies provided these vaccinations, and frontline staff could help to raise awareness. Conclusion: Funded maternal vaccinations in pharmacies are generally well accepted and provide an opportunity to increase uptake and prevent disease.