Australian vaccine preventable disease epidemiological review series: diphtheria 1999-2019.

Background: Diphtheria is rare in Australia, but an increasing number of cases have been notified in recent years. Alongside notifications from 1999 to 2019, we analysed other relevant national data sources to evaluate trends over the past two decades. Methods: Diphtheria notifications (National Notifiable Diseases Surveillance System [NNDSS]), hospitalisations (National Hospital Morbidity Database [NHMD]) and deaths (Australian Bureau of Statistics and the Australian Coordinating Registry) were separately analysed by site of infection, age group, sex, state/territory, Aboriginal and Torres Strait Islander status, and vaccination status. Results: During the study period, eight (0.002 per 100,000 population per year) cases of respiratory diphtheria and 38 (0.008 per 100,000 population per year) cases of cutaneous diphtheria were recorded in the NNDSS, with 45/46 reported in the nine years since 2011. Corynebacterium diphtheriae accounted for 87% of notified cases, who had a median age of 31.5 years (respiratory diphtheria) and 52.5 years (cutaneous diphtheria); no respiratory diphtheria was notified in those under 15 years of age. A majority of the cutaneous diphtheria cases (27/38; 71%) were acquired overseas, as were 3/8 (38%) of the respiratory diphtheria cases. Rates of both presentation types were higher in Aboriginal and Torres Strait Islander people (respiratory: 0.007 per 100,000 population per year; cutaneous: 0.021 per 100,000 population per year) than were rates in the overall population. Queensland had the highest rate of notified respiratory cases (0.007 per 100,000 population per year), and the Northern Territory the highest rate of cutaneous notifications (0.043 per 100,000 population per year). There were 29 hospitalisations with a principal-diagnosis diphtheria code in the NHMD between 2002 and 2018, of which eight were designated as respiratory (0.002 per 100,000 population per year), eight as cutaneous (0.002 per 100,000 population per year), and 13 with an unknown site of infection. Among notified cases, two deaths were reported in unvaccinated people in Queensland. Conclusions: Although diphtheria remains rare in Australia, 45 cases were notified in the years 2011-2019, compared with one case between 1999 and 2010. Robust surveillance remains important to detect all cases. High immunity will need to be maintained across all age groups to prevent outbreaks, and travel and adult booster doses should be encouraged.

The short term safety of COVID-19 vaccines in Australia: AusVaxSafety active surveillance, February - August 2021.

OBJECTIVE: To assess the short term safety of the COVID-19 vaccines Comirnaty (Pfizer-BioNTech BNT162b2) and Vaxzevria (AstraZeneca ChAdOx1) in Australia. DESIGN: Prospective observational cohort study; online surveys by AusVaxSafety, a national active vaccine safety surveillance system, three and eight days after vaccination. SETTING, PARTICIPANTS: People aged 16 years or more who received COVID-19 vaccines at sentinel vaccination hubs, general practices, or Aboriginal Community Controlled Health Organisation clinics, 22 February - 30 August 2021. MAIN OUTCOME MEASURES: Primary outcome: proportion of respondents who reported any adverse event following immunisation (AEFI) 0-3 days after vaccination. SECONDARY OUTCOMES: proportions of respondents who reported specific adverse events or medical review for AEFI within seven days of vaccination; impact on usual daily activities; recovery. RESULTS: 4 851 480 people received COVID-19 vaccines at participating sentinel sites during the study period (25% of all COVID-19 vaccine doses administered in Australia to 30 August 2021). 3 035 983 people responded to both surveys (response rate, 62.6%); 35.9% of respondents reported one or more AEFI 0-3 days after Comirnaty dose 1, 54.7% after Comirnaty dose 2, 52.8% after Vaxzevria dose 1, and 22.0% after Vaxzevria dose 2. Local pain, fatigue, headache, and myalgia were the most frequently reported symptoms. After adjusting for demographic characteristics, vaccination site type, jurisdiction, and self-reported medical conditions, the odds of reporting any AEFI were higher for women than men (range of adjusted odd ratios [aORs], by vaccine and dose, 1.53-1.84), for people with a history of anaphylaxis (aOR range, 1.28-1.45), and for people reporting certain underlying conditions, including obesity (aOR range, 1.15-1.75), immunodeficiency (aOR range, 1.04-2.24), or chronic inflammatory disease (aOR range, 1.05-1.75). 0.9% of respondents sought medical advice in the three days following vaccination, most frequently after Comirnaty dose 2 (1.4%) and Vaxzevria dose 1 (1.2%). CONCLUSION: AusVaxSafety active surveillance affirms the short term safety profile of Comirnaty and Vaxzevria vaccines in a large population sample during the first six months of the Australian COVID-19 vaccination program.

Australian vaccine preventable disease epidemiological review series: measles, 2012-2019.

Background: Data sources, relevant to measles epidemiology from 2012 to 2019, were reviewed in the context of Australia's certification, by the World Health Organization in 2014, of the elimination of measles. Methods: Data on measles notifications, hospitalisations, and deaths were obtained from the National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and the Australian Coordinating Registry. Data were analysed by age group, state/territory, Aboriginal and Torres Strait Islander status, genotype, place of acquisition, source of infection (importation status), and vaccination status. Results: Between 2012 and 2019, there were 1,337 measles notifications (average annual notifications 0.7 per 100,000 population per year) and 425 hospitalisations with measles as principal diagnosis (0.3 per 100,000 population per year) were recorded. The highest annual notification rate was in 2014, when the rate in the Northern Territory was 21.4 per 100,000 population per year. Although notification and hospitalisation rates were highest in infants < 12 months (respectively 5.8 and 2.1 per 100,000 population per year), people aged 10 to 39 years (10-19y: 272 notifications; 20-29y: 347; 30-39y: 266) accounted for 66% of notified cases. Of cases with a known vaccination status, only 20/169 (11.8%) of those aged 1-9 years had received at least one dose of measles-containing vaccine, compared with 215/571 (37.7%) of those aged 10-39 years. Persons born before 1966 (at least 47 years of age during the study period) are likely to have immunity from wild-type measles infection and had the lowest notification rates in each year. Of notified cases, 98.1% were imported or import related, and of the 900 measles viruses genotyped, D8 and B3 accounted for 89.1%. Conclusion: This review's findings of low measles incidence, in the presence of robust surveillance and high two-dose measles vaccination coverage, provide evidence of continued elimination of endemic measles in Australia, with almost all cases imported or epidemiologically linked to an imported case. Most cases eligible for vaccination are unvaccinated, which should remain the primary focus for prevention. Potential waning immunity in older age groups requires monitoring. Continued high population immunity and high-quality public health response to cases will be needed to maintain Australia's elimination status, particularly once international borders reopen.

Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibodies in Australia After the First Epidemic Wave in 2020: A National Survey.

BACKGROUND: As of mid-2021, Australia's only nationwide coronavirus disease 2019 (COVID-19) epidemic occurred in the first 6 months of the pandemic. Subsequently, there has been limited transmission in most states and territories. Understanding community spread during the first wave was hampered by initial limitations on testing and surveillance. To characterize the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroprevalence generated during this time, we undertook Australia's largest national SARS-CoV-2 serosurvey. METHODS: Between June 19 and August 6, 2020, residual specimens were sampled from people undergoing general pathology testing (all ages), women attending antenatal screening (20-39 years), and blood donors (20-69 years) based on the Australian population's age and geographic distributions. Specimens were tested by Wantai total SARS-CoV-2-antibody assay. Seroprevalence estimates adjusted for test performance were produced. The SARS-CoV-2 antibody-positive specimens were characterized with microneutralization assays. RESULTS: Of 11 317 specimens (5132 general pathology; 2972 antenatal; 3213 blood-donors), 71 were positive for SARS-CoV-2-specific antibodies. Seroprevalence estimates were 0.47% (95% credible interval [CrI], 0.04%-0.89%), 0.25% (CrI, 0.03%-0.54%), and 0.23% (CrI, 0.04%-0.54%), respectively. No seropositive specimens had neutralizing antibodies. CONCLUSIONS: Australia's seroprevalence was extremely low (<0.5%) after the only national COVID-19 wave thus far. These data and the subsequent limited community transmission highlight the population's naivety to SARS-CoV-2 and the urgency of increasing vaccine-derived protection.

Australian vaccine preventable disease epidemiological review series: Pertussis, 2013-2018.

INTRODUCTION: Significant recent changes in Australian pertussis immunisation policy include the progressive introduction of funded pertussis immunisation programs for pregnant women, from late 2014 to mid-2015 at jurisdictional level and then under the National Immunisation Program from July 2018, and reintroduction of the 18-month booster dose in 2016. This study analyses pertussis notification, hospitalisation, and mortality data from 2013 to 2018 in the context of trends since 1995. METHODS: This study used data from the National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and the Australian Coordinating Registry, for descriptive analysis of pertussis notifications, hospitalisations and deaths in Australia by Aboriginal and Torres Strait Islander (Indigenous) status from 2013 to 2018, examining trends between 1995 and 2012 at both the national and jurisdictional level. Incidence rate ratios (IRR) were utilised to compare pertussis incidence in infants aged < 2 months and 6-11 months for each year from the 2015-2018 (post-maternal-vaccination) period against the 2010-2013 (pre-maternal-vaccination) period. RESULTS AND DISCUSSION: Annual national all-age incidence of pertussis notifications between 2013 and 2018 was 63.6 per 100,000 population, 40% less than between 2006 and 2012. Between 2016 and 2018, infants aged < 2 months had the lowest notification rates of age groups < 5 years old, with the highest notification rates in pre-adolescents aged 9-11 years. Compared with the baseline period (2010-2013), the IRR for infants aged < 2 months decreased in each year during the post-maternal-vaccination period from 0.4 (95% confidence interval [95% CI]: 0.3-0.5) in 2015 to 0.1 (95% CI: 0.1-0.2) in 2018. For infants aged 6-11 months, the IRR was 0.9 (95% CI: 0.8-1.0) in 2015, 1.1 (95% CI: 1.0-1.2) in 2016 and declined to 0.7 (95% CI: 0.6-0.8) in 2017 and 2018. Notification and hospitalisation rates in Indigenous children were 3-8 times as high as rates in non-Indigenous children across all age groups < 5 years old. CONCLUSION: Pertussis remains the second most frequently notified vaccine preventable disease in Australia, after influenza, but dramatic decreases in incidence have been observed in infants too young to receive any doses of pertussis-containing vaccine.

Risk factors and disease severity in Australian infants aged under 6 months hospitalised with influenza 2011-2019.

AIM: Infants aged <6 months are vulnerable to severe influenza disease and no vaccine is approved for use in this age group. We aimed to describe the epidemiology, risk factors associated with severe outcomes and management of influenza in Australian infants aged <6 months. METHODS: Incident cases aged <6 months of laboratory-confirmed influenza were captured through two national active prospective sentinel hospital-based surveillance systems in Australia from 2011 to 2019, inclusive. Demographic and clinical features, disease risk factors and outcomes (intensive care unit (ICU) admission and length of stay) and oseltamivir use were analysed. The proportion of infant influenza hospitalisations and nosocomial cases among all hospitalisations were also reported. RESULTS: Of 680 hospitalised infants aged <6 months, 57.9% were male and 14.5% were Indigenous Australian. Median age was 2.6 months, 19.2% were born premature and 19.0% had a comorbidity, excluding prematurity. Overall, 77.9% had influenza A. Nosocomial cases accounted for 7.8%. ICU admission occurred in 14.7% and oseltamivir was prescribed for 18.8%. Factors associated with ICU admission included age <1 month (adjusted odds ratio (aOR) 3.95, 95% confidence interval (CI): 1.47-10.60), comorbidity (aOR 7.69, 95% CI: 4.04-14.64) and prematurity (aOR 2.60, 95% CI: 1.40-4.81). The proportion of infants with influenza among all infant hospitalisations ranged 1.0-2.6% in the 2019 influenza season. CONCLUSION: Infants aged <6 months, and particularly neonates, experience serious disease from influenza. This data underpins the need for preventative strategies such as maternal immunisation and continued investigation into the possibility of safe and efficacious vaccination prior to 6 months of age.

Pertussis Disease and Antenatal Vaccine Effectiveness in Australian Children.

BACKGROUND: Population-level studies of severe pertussis extending beyond infancy are sparse, and none in the context of antenatal vaccination. We compared hospitalized pertussis cases from birth to 15 years of age before and after introduction of antenatal immunization. METHODS: Active surveillance of laboratory-confirmed pertussis hospitalizations in a national network of pediatric hospitals in Australia January 2012 to June 2019. Impact of maternal vaccination was assessed by vaccine effectiveness (VE) in cases and test-negative controls with <2 months of age and by before-after comparison of age distribution of cases. Among cases eligible for one or more vaccine doses, we examined proportions age-appropriately immunized and with comorbidities by age group. RESULTS: Among 419 eligible cases, the proportion <2 months of age significantly decreased from 33.1% in 2012 to 2014 compared with 19.6% in 2016 to 2019 when mothers of only 4 of 17 (23.5%) cases <2 months of age had received antenatal vaccination. VE was estimated to be 84.3% (95% CI, 26.1-96.7). Across all years (2012-2019), of 55 cases 4-11 months of age, 21 (38%) had ≥2 vaccine doses, whereas among 155 cases ≥12 months of age, 122 (85.2%) had ≥3 vaccine doses. Prevalence of comorbidities (primarily cardiorespiratory) increased from 5 (2.1%) <6 months of age to 36 (24.2%) ≥12 months of age (P < 0.001), with 6/16 (38%) cases ≥12 months of age who required intensive care having comorbidities. CONCLUSIONS: Below the age of 12 months, prevention of severe pertussis will be maximized by high maternal antenatal vaccine uptake and timeliness of infant vaccine doses. Despite full immunization, we found children ≥12 months of age accounted for 27% of hospitalizations <15 years, with 24% having comorbities, suggesting new vaccine strategies, such as additional doses or more immunogenic vaccines, require evaluation.

Paediatric Active Enhanced Disease Surveillance (PAEDS) 2019: Prospective hospital-based surveillance for serious paediatric conditions.

INTRODUCTION: The Paediatric Active Enhanced Disease Surveillance (PAEDS) network is an Australian hospital-based active surveillance system employing prospective case ascertainment for selected serious childhood conditions, particularly vaccine preventable diseases and potential adverse events following immunisation (AEFI). This report presents surveillance data for 2019. METHODS: Specialist nurses screened hospital admissions, emergency department records, laboratory and other data on a daily basis in seven paediatric tertiary referral hospitals across Australia, to identify children with the conditions under surveillance. Standardised protocols and case definitions were used across all sites. In 2019, the conditions under surveillance comprised: acute flaccid paralysis (AFP; a syndrome associated with poliovirus infection), acute childhood encephalitis (ACE), influenza, intussusception (IS; a potential AEFI with rotavirus vaccines), pertussis, varicella-zoster virus infection (varicella and herpes zoster), invasive meningococcal and invasive Group A streptococcus diseases and two new conditions, Kawasaki disease and gram-negative bloodstream infections. An additional social research component continued to evaluate parental attitudes to influenza vaccination. RESULTS: PAEDS captured 2,701 cases for 2019 across all conditions under surveillance. Key outcomes of PAEDS included: contribution to national AFP surveillance to reach the World Health Organization reporting targets for detection of poliomyelitis cases; demonstration of high influenza activity in 2019 and influenza-associated deaths in ACE cases; identification of key barriers to influenza vaccination of children hospitalised for acute respiratory illness; reporting of all IS cases associated with vaccine receipt to relevant state health department; and showing a further reduction nationally in varicella cases. Enhanced pertussis surveillance continued to capture controls to support vaccine efficacy estimation. Invasive meningococcal disease surveillance showed predominance of serotype B and a reduction in cases nationally. Surveillance for invasive group A streptococcus captured severe cases in children. Monitoring of Kawasaki disease incidence and gram-negative bloodstream infections commenced. CONCLUSIONS: PAEDS continues to provide unique policy-relevant data on serious paediatric conditions using sentinel hospital-based enhanced surveillance. Keywords: paediatric, surveillance, child, hospital, vaccine preventable diseases, adverse event following immunisation, acute flaccid paralysis, encephalitis, influenza, intussusception, pertussis, varicella zoster virus, meningococcal, group A streptococcus, Kawasaki, bloodstream infections.

Seroprevalence of SARS-CoV-2-specific antibodies in Sydney after the first epidemic wave of 2020.

OBJECTIVES: To estimate SARS-CoV-2-specific antibody seroprevalence after the first epidemic wave of coronavirus disease 2019 (COVID-19) in Sydney. SETTING, PARTICIPANTS: People of any age who had provided blood for testing at selected diagnostic pathology services (general pathology); pregnant women aged 20-39 years who had received routine antenatal screening; and Australian Red Cross Lifeblood plasmapheresis donors aged 20-69 years. DESIGN: Cross-sectional study; testing of de-identified residual blood specimens collected during 20 April - 2 June 2020. MAIN OUTCOME MEASURE: Estimated proportions of people seropositive for anti-SARS-CoV-2-specific IgG, adjusted for test sensitivity and specificity. RESULTS: Thirty-eight of 5339 specimens were IgG-positive (general pathology, 19 of 3231; antenatal screening, 7 of 560; plasmapheresis donors, 12 of 1548); there were no clear patterns by age group, sex, or location of residence. Adjusted estimated seroprevalence among people who had had general pathology blood tests (all ages) was 0.15% (95% credible interval [CrI], 0.04-0.41%), and 0.29% (95% CrI, 0.04-0.75%) for plasmapheresis donors (20-69 years). Among 20-39-year-old people, the age group common to all three collection groups, adjusted estimated seroprevalence was 0.24% (95% CrI, 0.04-0.80%) for the general pathology group, 0.79% (95% CrI, 0.04-1.88%) for the antenatal screening group, and 0.69% (95% CrI, 0.04-1.59%) for plasmapheresis donors. CONCLUSIONS: Estimated SARS-CoV-2 seroprevalence was below 1%, indicating that community transmission was low during the first COVID-19 epidemic wave in Sydney. These findings suggest that early control of the spread of COVID-19 was successful, but efforts to reduce further transmission remain important.

Barriers to influenza vaccination of children hospitalised for acute respiratory illness: A cross-sectional survey.

AIM: To identify barriers to influenza vaccination of children hospitalised for acute respiratory illness in Australia. METHODS: A total of 595 parents of children hospitalised with acute respiratory illness across five tertiary hospitals in 2019 participated in an online survey. Multivariate logistic regression identified factors most strongly associated with influenza vaccination barriers. RESULTS: Odds of influenza vaccination were lower with lack of health-care provider (HCP) recommendation (adjusted odds ratio (aOR) 0.18; 95% confidence interval (CI): 0.08-0.38); if parents had difficulties (aOR 0.19; 95% CI: 0.08-0.47) or were 'neutral' (aOR 0.23; 95% CI: 0.06-0.82) in remembering to make an appointment; and if parents had difficulties (aOR 0.21; 95% CI: 0.07-0.62) or were 'neutral' (aOR 0.24; 95% CI: 0.07-0.79) regarding getting an appointment for vaccination. Odds were also lower if parents did not believe (aOR 0.27; 95% CI: 0.08-0.90) or were 'neutral' (aOR 0.15; 95% CI: 0.04-0.49) regarding whether the people most important to them would have their child/ren vaccinated against influenza. Children had lower odds of vaccination if parents did not support (aOR 0.09; 95% CI: 0.01-0.82) or were ambivalent (aOR 0.09; 95% CI: 0.01-0.56) in their support for influenza vaccination. Finally, lack of history of influenza vaccination of child (aOR 0.38; 95% CI: 0.18-0.81) and respondent (aOR 0.25; 95% CI: 0.11-0.56) were associated with lack of receipt of influenza vaccine before admission for acute respiratory infection. CONCLUSIONS: Assisting parents in remembering and accessing influenza vaccination and encouraging health-care providers to recommend vaccination may increase uptake.

Transmission of SARS-CoV-2 in Australian educational settings: a prospective cohort study.

BACKGROUND: School closures have occurred globally during the COVID-19 pandemic. However, empiric data on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and in educational settings are scarce. In Australia, most schools have remained open during the first epidemic wave, albeit with reduced student physical attendance at the epidemic peak. We examined SARS-CoV-2 transmission among children and staff in schools and early childhood education and care (ECEC) settings in the Australian state of New South Wales (NSW). METHODS: Laboratory-confirmed paediatric (aged ≤18 years) and adult COVID-19 cases who attended a school or ECEC setting while considered infectious (defined as 24 h before symptom onset based on national guidelines during the study period) in NSW from Jan 25 to April 10, 2020, were investigated for onward transmission. All identified school and ECEC settings close contacts were required to home quarantine for 14 days, and were monitored and offered SARS-CoV-2 nucleic acid testing if symptomatic. Enhanced investigations in selected educational settings included nucleic acid testing and SARS-CoV-2 antibody testing in symptomatic and asymptomatic contacts. Secondary attack rates were calculated and compared with state-wide COVID-19 rates. FINDINGS: 15 schools and ten ECEC settings had children (n=12) or adults (n=15) attend while infectious, with 1448 contacts monitored. Of these, 633 (43·7%) of 1448 had nucleic acid testing, or antibody testing, or both, with 18 secondary cases identified (attack rate 1·2%). Five secondary cases (three children; two adults) were identified (attack rate 0·5%; 5/914) in three schools. No secondary transmission occurred in nine of ten ECEC settings among 497 contacts. However, one outbreak in an ECEC setting involved transmission to six adults and seven children (attack rate 35·1%; 13/37). Across all settings, five (28·0%) of 18 secondary infections were asymptomatic (three infants [all aged 1 year], one adolescent [age 15 years], and one adult). INTERPRETATION: SARS-CoV-2 transmission rates were low in NSW educational settings during the first COVID-19 epidemic wave, consistent with mild infrequent disease in the 1·8 million child population. With effective case-contact testing and epidemic management strategies and associated small numbers of attendances while infected, children and teachers did not contribute significantly to COVID-19 transmission via attendance in educational settings. These findings could be used to inform modelling and public health policy regarding school closures during the COVID-19 pandemic. FUNDING: NSW Government Department of Health.

Paediatric Active Enhanced Disease Surveillance (PAEDS) 2017 and 2018: Prospective hospital-based surveillance for serious paediatric conditions.

Introduction: The Paediatric Active Enhanced Disease Surveillance (PAEDS) network is a hospital-based active surveillance system employing prospective case ascertainment for selected serious childhood conditions, particularly vaccine-preventable diseases and potential adverse events following immunisation (AEFI). This report presents surveillance data for 2017 and 2018. Methods: Specialist nurses screened hospital admissions, emergency department (ED) records, laboratory and other data on a daily basis in seven paediatric tertiary referral hospitals across Australia to identify children with the conditions under surveillance. In 2017 and 2018 these included acute flaccid paralysis (AFP; a syndrome associated with poliovirus infection), acute childhood encephalitis (ACE), influenza, intussusception (IS; a potential AEFI with rotavirus vaccines), pertussis, varicella-zoster virus infection (varicella and herpes zoster), invasive meningococcal, and invasive Group A streptococcus diseases. An additional social research component was added to evaluate parental attitudes to vaccination. Results: PAEDS captured 1,580 and 925 cases for 2017 and 2018, respectively, across all conditions under surveillance. Key outcomes of PAEDS included: contribution to national AFP surveillance to reach the World Health Organization reporting targets; identification of a third human parechovirus outbreak among other infectious diseases linked to ACE; demonstration of variable influenza activity between 2017 and 2018, with vaccine effectiveness (VE) analysis demonstrating that the protection offered through vaccination is season-dependent. All IS cases associated with vaccine receipt were reported to the relevant state health department. Varicella and herpes zoster case numbers remained unchanged, with vaccine uptake found to be suboptimal among eligible children under the NIP. Enhanced pertussis surveillance continues to capture controls for VE estimation. Surveillance for invasive meningococcal disease showed predominance for serotype B at 57% over 2 years among 77 cases where serotyping was available, and surveillance for invasive group A streptococcus captured severe disease in children. Conclusion: PAEDS continues to provide unique policy-relevant data on serious paediatric conditions using hospital-based sentinel surveillance.

Comparative Postmarket Safety Profile of Adjuvanted and High-Dose Influenza Vaccines in Individuals 65 Years or Older.

Importance: Every year, influenza vaccines are administered to millions of people worldwide to reduce morbidity and mortality from influenza. As new vaccine formulations are increasingly used, monitoring and comparing safety, in addition to vaccine effectiveness, in target populations are essential. Objective: To assess the postmarketing safety profile of 2018 Southern Hemisphere influenza vaccines, particularly 2 new enhanced trivalent inactivated influenza vaccines: an adjuvanted trivalent inactivated influenza vaccine (aIIV3) and high-dose trivalent inactivated influenza vaccine (HD-IIV3), among Australian individuals 65 years or older. Design, Setting, and Participants: This cohort study used solicited short message service-based self-reported survey data on adverse events occurring within 3 to 5 days after receipt of an influenza vaccination. Participants included individuals 65 years or older who received routinely recommended influenza vaccines at 1 of 265 sentinel immunization sites, including primary care, hospital, and community-based clinics, participating in Australia's AusVaxSafety active vaccine safety surveillance system from April 1 to August 31, 2018. Data were analyzed from September 1, 2018, to June 30, 2019. Exposure: Any licensed 2018 influenza vaccine administered in clinical practice. Main Outcomes and Measures: Rates (overall, by brand, and by concomitant vaccine receipt) of adverse events, including medical attendance as a proxy for serious adverse events. Results: Of 72 013 individuals 65 years or older who received an influenza vaccine in 2018, 50 134 individuals (69.6%) responded to the initial survey regarding adverse events experienced after vaccination (median [interquartile range] age, 71 [68-76] years; 27 056 [54.0%] women). Most individuals received an enhanced trivalent inactivated influenza vaccine, including 28 003 individuals (55.9%) who received aIIV3 and 19 306 individuals (38.5%) who received HD-IIV3; 2208 individuals (4.4%) received a quadrivalent inactivated influenza vaccine. Individuals who received HD-IIV3 reported significantly higher rates of any adverse event compared with individuals who received aIIV3 (1716 individuals [8.9%] vs 1796 individuals [6.4%]; P < .001) as well as specific adverse events, including fever (195 individuals [1.1%] vs 164 individuals [0.6%]; P < .001), injection site pain (383 individuals [2.1%] vs 350 individuals [1.3%]; P < .001), and injection site swelling or redness (256 individuals [1.4%] vs 248 individuals [0.9%]; P < .001). Adverse event rates reported by those receiving any quadrivalent inactivated influenza vaccine were similar to rates reported by those receiving aIIV3. Rates of medical care seeking for adverse events associated with aIIV3 and HD-IIV3 were low and comparable (80 individuals [0.3%] vs 56 individuals [0.3%]; P = .91). Conclusions and Relevance: The findings of this large-scale participant-based postmarketing assessment of the safety of 2 new enhanced influenza vaccines used in individuals 65 years or older provide reassuring near-real-time and cumulative data to inform and support confidence in ongoing vaccine use.

Whole-Cell Pertussis Vaccination and Decreased Risk of IgE-Mediated Food Allergy: A Nested Case-Control Study.

BACKGROUND: Rates of food allergy have increased markedly in Australia and other high- income countries in recent years. On the basis of ecological observations, and the known immunologic characteristics of whole-cell pertussis (wP) compared with acellular pertussis (aP) vaccines, we hypothesized that wP vaccination in infancy protects against the development of food allergy. OBJECTIVE: To determine whether infants who receive wP in infancy were less likely to develop IgE-mediated food allergy than those who received aP. METHODS: Retrospective cohort-nested case-control study of Australian children born in the period 1997 to 1999, the period of transition from using wP-containing to aP-containing vaccines. Children diagnosed with IgE-mediated food allergy were individually matched to 10 controls by date of birth, socioeconomic decile, and jurisdiction of birth. The odds ratio of vaccination with wP versus aP among cases and matched controls was calculated using conditional logistic regression. RESULTS: The odds ratio of receiving the first dose as wP (rather than aP) among cases of food allergy compared with controls was 0.77 (95% CI, 0.62-0.95). The results of secondary analyses (any dose as wP vs aP-only, and wP-only vs aP-only) were broadly similar. CONCLUSIONS: Australian infants who received wP vaccines were less likely to be diagnosed with food allergy in childhood than contemporaneous children who received aP vaccines. If a protective effect is confirmed in a randomized controlled trial, wP or mixed wP and aP vaccination schedules could form part of an effective strategy for combating the rise in food allergies.

Tetanus Immunity and Epidemiology in Australia, 1993-2010.

BACKGROUND: This study evaluates trends in tetanus immunity and epidemiology over the last two decades in Australia, drawing on two national serological surveys and national tetanus morbidity data, to justify current Australian adult tetanus booster recommendations. METHODS: We compare tetanus immunity level between two national serosurveys, and examine incidence trends using the most accurate estimation of the true number of cases by correcting for under-ascertainment. RESULTS: Tetanus immunity in people aged <60 years is high, but the elderly, particularly the female elderly, may not be adequately protected. Over the past twenty years older people have regularly accounted for the highest number of tetanus cases, with an increasing proportion of cases. CONCLUSION: Despite a positive decrease in tetanus incidence, there remains a significant burden in the elderly population of an entirely preventable disease. Supplying a funded booster dose of dTpa at 65 years would be, potentially, an effective strategy to prevent tetanus cases in Australia.

Diphtheria Immunity in Australia: Should we be Concerned?

OBJECTIVES: We report the results of the 2007 national serological survey of immunity to diphtheria in Australia to assess the impact of recent schedule changes on diphtheria immunity, and the adequacy of current policy in the context of increased international travel of people and pathogens. METHODS: Residual sera (n =1656) collected opportunistically from Australian laboratories in 2007 were tested for diphtheria antibody levels using an enzyme immunoassay, with the protective threshold defined as ≥0.1 IU/mL. About 40% of adults aged ≥30 years are susceptible to diphtheria; following the removal of the 18-month booster and its replacement with a dose in adolescence offered through school-based dTpa vaccination program, 59% of children aged 3 years were susceptible to diphtheria, whilst adolescents demonstrated improved immunity. RESULTS: There is no apparent boosting of diphtheria immunity from meningococcal group C conjugate (MCC) or seven-valent pneumococcal conjugate (7vPCV) vaccines in relevant age groups. CONCLUSION: Australians who travel to diphtheria-endemic areas should be up-to-date with their vaccinations. Close monitoring of population immunity levels against diphtheria remains important to ensure that immunity does not decline to a level where wide-spread transmission would be possible.

Hepatitis B Seroepidemiology in Australia, One Decade After Universal Vaccination of Infants and Adolescents.

BACKGROUND: This study assessed the impact of the staged introduction of universal infant and adolescent catch-up hepatitis B vaccination programs on the prevalence of immunity and past hepatitis B virus (HBV) infection in targeted cohorts over almost a decade in Australia. METHODS: We compared the prevalence of immunity in relevant cohorts of children and adolescents in repeated national serological surveys conducted in 1998-99, 2002 and 2007. Residual sera (n =2210) collected opportunistically from Australian laboratories in 2007 were tested for antibody to hepatitis B surface antigen (anti-HBs) indicating vaccine-induced immunity; sera from individuals aged 12-29 years with anti-HBs detected (n =386) were then tested for hepatitis B core antibody (anti-HBc) to identify past hepatitis B infection. RESULTS: In 2007, compared with the baseline period of 1998-99, anti-HBs prevalence had increased significantly in all age groups below 24 years, by more than double in target children. Prevalence of anti-HBc was zero in the 12-14 years and reduced by 71% in those aged 15-19 years. The hepatitis B vaccination protected a significant number of targeted adolescents with a modest vaccine uptake (57% to 60% nationally). CONCLUSION: In a setting without incentives or school entry requirements, adolescent vaccination coverage was significantly higher when delivered by school-based rather than GP-based mechanisms. A cohort of children was growing up in Australia with a high prevalence of vaccineinduced immunity against hepatitis B, providing the best opportunity for controlling HBV infection in Australia.

Effectiveness of Acellular Pertussis Vaccine in Older Adults: Nested Matched Case-control Study.

BACKGROUND: Despite recommendations that older adults receive acellular pertussis vaccines, data on direct effectiveness in adults aged over 50 years are sparse. METHODS: A case-control study nested within an adult cohort. Cases were identified from linked pertussis notifications and each matched to 3 controls on age, sex, and cohort recruitment date. Cases and controls were invited to complete a questionnaire, with verification of vaccination status by their primary care provider. Vaccine effectiveness (VE) was estimated by conditional logistic regression, with adjustment for reported contact with children and area of residence. RESULTS: Of 1112 notified cases in the cohort, we had complete data for 333 cases and 506 controls. Among 172 PCR-diagnosed cases (mean age, 61 years), 11.2% versus 19.5% of controls had provider-verified pertussis vaccination, on average, 3.2 years earlier. Adjusted VE against PCR-diagnosed pertussis was 52% (95% CI, 15-73%), nonsignificantly higher if vaccinated within 2 years (63%; -5-87%). Adjusted VE was similar in adults born before 1950, presumed primed by natural infection (51%; -8-77%) versus those born 1950 or later who may have received whole-cell pertussis vaccine (53%; -11-80%) (P-heterogeneity = 0.9). Among 156 cases identified by single-point serology, adjusted VE was -55% (-177-13%). CONCLUSIONS: We found modest protection against PCR-confirmed pertussis among older adults (mean age, 61 years; range, 46-81 years) within 5 years after acellular vaccine. The most likely explanation for the markedly divergent VE estimate from cases identified by single-titer serology is misclassification arising from limited diagnostic specificity in our setting.

Rotavirus Epidemiology and Monovalent Rotavirus Vaccine Effectiveness in Australia: 2010-2017.

BACKGROUND: Rotavirus vaccine has been funded for infants under the Australian National Immunisation Program since 2007, with Rotarix vaccine used in New South Wales, Australia, from that time. In 2017, New South Wales experienced a large outbreak of rotavirus gastroenteritis. We examined epidemiology, genotypic profiles, and vaccine effectiveness (VE) among cases. METHODS: Laboratory-confirmed cases of rotavirus notified in New South Wales between January 1, 2010 and December 31, 2017 were analyzed. VE was estimated in children via a case-control analysis. Specimens from a sample of hospitalized case patients were genotyped and analyzed. RESULTS: In 2017, 2319 rotavirus cases were reported, representing a 3.1-fold increase on the 2016 notification rate. The highest rate was among children aged <2 years. For notified cases in 2017, 2-dose VE estimates were 88.4%, 83.7%, and 78.7% in those aged 6 to 11 months, 1 to 3 years, and 4 to 9 years, respectively. VE was significantly reduced from 89.5% within 1 year of vaccination to 77.0% at 5 to 10 years postvaccination. Equinelike G3P[8] (48%) and G8P[8] (23%) were identified as the most common genotypes in case patients aged ≥6 months. CONCLUSIONS: Rotarix is highly effective at preventing laboratory-confirmed rotavirus in Australia, especially in infants aged 6 to 11 months. Reduced VE in older age groups and over time suggests waning protection, possibly related to the absence of subclinical immune boosting from continuously circulating virus. G8 genotypes have not been common in Australia, and their emergence, along with equinelike G3P[8], may be related to vaccine-induced selective pressure; however, further strain-specific VE studies are needed.