B Part of It School Leaver Study: A Repeat Cross-Sectional Study to Assess the Impact of Increasing Coverage With Meningococcal B (4CMenB) Vaccine on Carriage of Neisseria meningitidis.

BACKGROUND: Recombinant protein-based vaccines targeting serogroup B meningococci protect against invasive disease but impacts on carriage are uncertain. This study assessed carriage prevalence of disease-associated meningococci in 2018-2020 as the proportion of vaccinated adolescents increased following introduction of a school-based 4CMenB immunization program. METHODS: Eligible participants who completed high school (aged 17-25) in South Australia in the previous year had an oropharyngeal swab taken and completed a risk factor questionnaire. Disease-associated meningococci (genogroups A, B, C, W, X, Y) were detected by meningococcal and genogroup-specific polymerase chain reaction. RESULTS: The analysis included 4104 participants in 2018, 2690 in 2019, and 1338 in 2020. The proportion vaccinated with 4CMenB increased from 43% in 2018, to 78% in 2019, and 76% in 2020. Carriage prevalence of disease-associated meningococci in 2018 was 225/4104 (5.5%). There was little difference between carriage prevalence in 2019 (134/2690, 5.0%; adjusted odds ratio [aOR], 0.82; 95% confidence interval [CI], .64-1.05) and 2020 (68/1338, 5.1%; aOR, 0.82; 95% CI, .57-1.17) compared to 2018. CONCLUSIONS: Increased 4CMenB uptake in adolescents was not associated with decline in carriage of disease-associated meningococci. 4CMenB immunization programs should focus on direct (individual) protection for groups at greatest risk of disease. CLINICAL TRIALS REGISTRATION: NCT03419533.

Impact of Meningococcal B Vaccine on Invasive Meningococcal Disease in Adolescents.

BACKGROUND: From 2017, a statewide cluster randomized trial was conducted in South Australia to assess the impact of the meningococcal B vaccine 4CMenB on pharyngeal Neisseria meningitidis carriage in adolescents. Senior schools were randomized to receive the vaccine in 2017 (intervention) or 2018 (control). In this study we report the vaccine impact of 4CMenB on serogroup B invasive meningococcal disease (IMD) in 16- to 19-year-old adolescents in South Australia. METHODS: This observational time series analysis of serogroup B IMD cases compares the 14 years prior to the commencement of the trial (2003-2016) with the 2 years following 4CMenB vaccination of the 2017 adolescent cohort. RESULTS: Approximately 62% of year 10 and 11 students (15-16 years old) in South Australia enrolled in the trial. A total of 30 522 year 10-12 students received at least 1 dose of 4CMenB. The number of serogroup B IMD cases in 16- to 19-year old adolescents in South Australia increased on average by 10% per year from 2003 to 2016 (95% confidence interval [CI], 6%-15%, P < .001), peaking with 10 cases in 2015. Serogroup B IMD cases reduced to 5 in 2017-2018 and 1 in 2018-2019, below the expected numbers of 9.9 (95% prediction interval [PI], 3.9-17.5) and 10.9 (95% PI, 4.4-19.1), respectively. This translated to an overall reduction in the number of serogroup B IMD cases of 71% (95% CI, 15%-90%, P = .02). There were no serogroup B IMD cases in vaccinated adolescents. CONCLUSIONS: Vaccinating adolescents with 4CMenB was associated with a reduction in group B meningococcal disease in South Australia. CLINICAL TRIALS REGISTRATION: NCT03089086.

Evaluating the effectiveness of the 4CMenB vaccine against invasive meningococcal disease and gonorrhoea in an infant, child and adolescent program: protocol.

Invasive meningococcal disease causes significant morbidity and mortality worldwide, with serogroup B being one of the predominant serogroups in Australia for many years. The South Australian (SA) State Government recently funded the introduction of a 4CMenB vaccination program for infants, children and adolescents. In addition to protecting against invasive meningococcal disease, emerging evidence suggests the 4CMenB vaccine may also be effective against gonorrhoea due to genetic similarities between Neisseria meningitidis and Neisseria gonorrhoeae. The proposed project aims to evaluate the effectiveness of the SA 4CMenB vaccination program against invasive meningococcal disease and gonorrhoea through a combination of observational studies using routine surveillance and research data. The main methodological approaches involve an interrupted time series regression model, screening, and case-control analyses with different sets of controls to estimate vaccine impact and effectiveness. These analyses are designed to minimize potential biases inherent in all observational studies and to provide critical data on the effectiveness of the 4CMenB vaccine against two diseases of major global public health concern.

Impact of Meningococcal B (4CMenB) Vaccine on Pharyngeal Neisseria meningitidis Carriage Density and Persistence in Adolescents.

BACKGROUND: Higher density of Neisseria meningitidis carriage may be associated with transmission of the meningococcus. Our aim was to establish the impact of meningococcal B (4CMenB) vaccine on N. meningitidis carriage density. METHODS: We compared 4CMenB vaccine to control among 913 South Australian students aged approximately 15-18 years in a cluster randomized trial who had N. meningitidis carriage at 12 months. Oropharyngeal swabs were collected at baseline and 12 months later to detect N. meningitidis carriage. Colony-forming units per milliliter (CFU/mL) were estimated by generating a standard curve that plotted quantitative polymerase chain reaction cycle threshold values against log-normalized CFU. RESULTS: Among the 913 students with N. meningitidis carriage at 12 months, there was no difference in mean carriage density between the vaccinated (n = 434; 3.80 log CFU/mL [standard deviation {SD}, 1.29]) and control group (n = 479; 3.73 log CFU/mL [SD, 1.30]; P = .51). Higher N. meningitidis carriage density at baseline was associated with an increase in the odds of persistent carriage at 12 months (n = 504; odds ratio [OR] per 1.0 log CFU/mL increase in density, 1.36 [95% confidence interval {CI}, 1.17-1.58]; P < .001). Students with baseline carriage who were vaccinated had decreased persistent N. meningitidis carriage at 12 months compared to unvaccinated students (81/260 [31%] vs 105/244 [43%]; OR, 0.60 [95% CI, .40-.90]; P = .01). CONCLUSIONS: 4CMenB vaccine did not reduce carriage density of N. meningitidis 12 months postvaccination, despite increased carriage clearance. Higher carriage density is likely to enable transmission through prolonged periods of population exposure. CLINICAL TRIALS REGISTRATION: NCT03089086.

Meningococcal B Vaccine and Meningococcal Carriage in Adolescents in Australia.

BACKGROUND: The meningococcal group B vaccine 4CMenB is a new, recombinant protein-based vaccine that is licensed to protect against invasive group B meningococcal disease. However, its role in preventing transmission and, therefore, inducing population (herd) protection is uncertain. METHODS: We used cluster randomization to assign, according to school, students in years 10 to 12 (age, 15 to 18 years) in South Australia to receive 4CMenB vaccination either at baseline (intervention) or at 12 months (control). The primary outcome was oropharyngeal carriage of disease-causing Neisseria meningitidis (group A, B, C, W, X, or Y) in students in years 10 and 11, as identified by polymerase-chain-reaction assays for PorA (encoding porin protein A) and N. meningitidis genogroups. Secondary outcomes included carriage prevalence and acquisition of all N. meningitidis and individual disease-causing genogroups. Risk factors for carriage were assessed at baseline. RESULTS: A total of 237 schools participated. During April through June 2017, a total of 24,269 students in years 10 and 11 and 10,220 students in year 12 were enrolled. At 12 months, there was no difference in the prevalence of carriage of disease-causing N. meningitidis between the vaccination group (2.55%; 326 of 12,746) and the control group (2.52%; 291 of 11,523) (adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.80 to 1.31; P = 0.85). There were no significant differences in the secondary carriage outcomes. At baseline, the risk factors for carriage of disease-causing N. meningitidis included later year of schooling (adjusted odds ratio for year 12 vs. year 10, 2.75; 95% CI, 2.03 to 3.73), current upper respiratory tract infection (adjusted odds ratio, 1.35; 95% CI, 1.12 to 1.63), cigarette smoking (adjusted odds ratio, 1.91; 95% CI, 1.29 to 2.83), water-pipe smoking (adjusted odds ratio, 1.82; 95% CI, 1.30 to 2.54), attending pubs or clubs (adjusted odds ratio, 1.54; 95% CI, 1.28 to 1.86), and intimate kissing (adjusted odds ratio, 1.65; 95% CI, 1.33 to 2.05). No vaccine safety concerns were identified. CONCLUSIONS: Among Australian adolescents, the 4CMenB vaccine had no discernible effect on the carriage of disease-causing meningococci, including group B. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT03089086.).

Factors Influencing Knowledge, Food Safety Practices and Food Preferences During Warm Weather of Salmonella and Campylobacter Cases in South Australia.

OBJECTIVE: To assess food safety practices, food shopping preferences, and eating behaviors of people diagnosed with Salmonella or Campylobacter infection in the warm seasons, and to identify socioeconomic factors associated with behavior and practices. METHODS: A cross-sectional survey was conducted among Salmonella and Campylobacter cases with onset of illness from January 1 to March 31, 2013. Multivariable logistic regression analyses examined relationships between socioeconomic position and food safety knowledge and practices, shopping and food preferences, and preferences, perceptions, and knowledge about food safety information on warm days. RESULTS: Respondents in our study engaged in unsafe personal and food hygiene practices. They also carried out unsafe food preparation practices, and had poor knowledge of foods associated with an increased risk of foodborne illness. Socioeconomic position did not influence food safety practices. We found that people's reported eating behaviors and food preferences were influenced by warm weather. CONCLUSIONS: Our study has explored preferences and practices related to food safety in the warm season months. This is important given that warmer ambient temperatures are projected to rise, both globally and in Australia, and will have a substantial effect on the burden of infectious gastroenteritis including foodborne disease. Our results provide information about modifiable behaviors for the prevention of foodborne illness in the household in the warm weather and the need for information to be disseminated across the general population. An understanding of the knowledge and factors associated with human behavior during warmer weather is critical for public health interventions on foodborne prevention.

Heatwaves differentially affect risk of Salmonella serotypes.

OBJECTIVES: Given increasing frequency of heatwaves and growing public health concerns associated with foodborne disease, we examined the relationship between heatwaves and salmonellosis in Adelaide, Australia. METHODS: Poisson regression analysis with Generalised Estimating Equations was used to estimate the effect of heatwaves and the impact of intensity, duration and timing on salmonellosis and specific serotypes notified from 1990 to 2012. Distributed lag non-linear models were applied to assess the non-linear and delayed effects of temperature during heatwaves on Salmonella cases. RESULTS: Salmonella typhimurium PT135 notifications were sensitive to the effects of heatwaves with a twofold (IRR 2.08, 95% CI 1.14-3.79) increase in cases relative to non-heatwave days. Heatwave intensity had a significant effect on daily counts of overall salmonellosis with a 34% increase in risk of infection (IRR 1.34, 95% CI 1.01-1.78) at >41 °C. The effects of temperature during heatwaves on Salmonella cases and serotypes were found at lags of up to 14 days. CONCLUSION: This study confirms heatwaves have a significant effect on Salmonella cases, and for the first time, identifies its impact on specific serotypes and phage types. These findings will contribute to the understanding of the impact of heatwaves on salmonellosis and provide insights that could mitigate their impact.

The changing epidemiology of Murray Valley encephalitis in Australia: the 2011 outbreak and a review of the literature.

Murray Valley encephalitis virus (MVEV) is the most serious of the endemic arboviruses in Australia. It was responsible for six known large outbreaks of encephalitis in south-eastern Australia in the 1900s, with the last comprising 58 cases in 1974. Since then MVEV clinical cases have been largely confined to the western and central parts of northern Australia. In 2011, high-level MVEV activity occurred in south-eastern Australia for the first time since 1974, accompanied by unusually heavy seasonal MVEV activity in northern Australia. This resulted in 17 confirmed cases of MVEV disease across Australia. Record wet season rainfall was recorded in many areas of Australia in the summer and autumn of 2011. This was associated with significant flooding and increased numbers of the mosquito vector and subsequent MVEV activity. This paper documents the outbreak and adds to our knowledge about disease outcomes, epidemiology of disease and the link between the MVEV activity and environmental factors. Clinical and demographic information from the 17 reported cases was obtained. Cases or family members were interviewed about their activities and location during the incubation period. In contrast to outbreaks prior to 2000, the majority of cases were non-Aboriginal adults, and almost half (40%) of the cases acquired MVEV outside their area of residence. All but two cases occurred in areas of known MVEV activity. This outbreak continues to reflect a change in the demographic pattern of human cases of encephalitic MVEV over the last 20 years. In northern Australia, this is associated with the increasing numbers of non-Aboriginal workers and tourists living and travelling in endemic and epidemic areas, and also identifies an association with activities that lead to high mosquito exposure. This outbreak demonstrates that there is an ongoing risk of MVEV encephalitis to the heavily populated areas of south-eastern Australia.

Toxigenic cutaneous diphtheria in a returned traveller.

Diphtheria is rarely reported in Australia. A case of cutaneous diphtheria was reported to the South Australian Department for Health and Ageing in April 2013 in an Australian-born 18-year-old female following travel in India. The case presented with a skin ulcer on her toe. Toxigenic Corynebacterium diphtheriae was isolated from a swab of the lesion. The case was treated with antibiotics. The public health response included infection control advice, assessing the case and household contacts for organism carriage and providing antimicrobial chemoprophylaxis to contacts. Although cutaneous diphtheria is not included as part of the Australian communicable disease surveillance case definition, this may be an oversight as international evidence demonstrates that it is a source of organism transmission and can potentially result in outbreaks among susceptible populations. This formed the rationale for the public health response to this particular case. The protocol for the public health management of diphtheria in South Australia has since been revised to include cutaneous lesions caused by the toxigenic strain of the organism as part of the surveillance case definition.

Mycobacterium chelonae abscesses associated with biomesotherapy, Australia, 2008.

An outbreak of skin abscesses occurred in Adelaide, Australia, in association with biomesotherapy, an alternative therapy practice. Mycobacterium chelonae was identified in 8 patient and 3 environmental samples. Our findings show M. chelonae infection can be associated with alternative therapies when infection-control breaches occur. Tighter regulations of alternative therapy practices are needed.

No evidence of increasing Haemophilus influenzae non-b infection in Australian Aboriginal children.

BACKGROUND: High, or increasing, rates of invasive Haemophilus influenzae (Hi) type a disease have been reported from North American native children from circumpolar regions, raising the question of serotype replacement being driven by vaccination against Hi type b (Hib). Indigenous Australians from remote areas had high rates of invasive Hib disease in the past, comparable to those in North American Indigenous populations. OBJECTIVE: Evaluate incidence rates of invasive Hi (overall and by serotype) in Indigenous Australian children over time. DESIGN: Descriptive study of Hi incidence rates by serotype, in the Northern Territory (NT) and South Australia (SA) from 2001 to 2011. Comparison of NT data with a study that was conducted in the NT in 1985-1988, before Hib vaccine was introduced. RESULTS: The average annual rate of invasive Hi type a (Hia) disease in Indigenous children aged < 5 years was 11/100,000 population. Although the incidence of Hi infection in Indigenous children in 2001-2003 was lower than during 2004-2011, this may be due to changes in surveillance. No other trend over time in individual serotypes or total invasive Hi disease, in Indigenous or non-Indigenous people, was identified. Compared to 1985-1988, rates in 2001-2011 were lower in all serotype groupings, by 98% for Hib, 75% for Hia, 79% for other serotypes and 67% for non-typeable Hi. CONCLUSIONS: There is no evidence of increases in invasive disease due to Hia, other specific non-b types, or non-typeable Hi in Australian Indigenous children. These data suggest that the increase in Hia some time after the introduction of Hib vaccine, as seen in the North American Arctic Region, is not common to all populations with high pre-vaccine rates of invasive Hib disease. However, small case numbers and the lack of molecular subtyping and PCR confirmation of pre-vaccine results complicate comparisons with North American epidemiology.

Pneumococcal disease in South Australia: vaccine success but no time for complacency.

BACKGROUND: Trends in age specific and serotype specific incidence rates for invasive pneumococcal disease (IPD) were examined in South Australia 4 years before and 5 years after the commencement of the Australian universal childhood 7 valent pneumococcal conjugate vaccine (7vPCV) program. METHODS: IPD cases were identified by routine enhanced surveillance. IPD serotypes were grouped according to those covered by the 7vPCV, the six serotypes specific to the 13 valent pneumococcal conjugate vaccine (13vPCV), the 11 serotypes specific to the 23 valent pneumococcal polysaccharide vaccine (23vPPV), as well as non-13vPCV and non-23vPPV groups. Poisson regression was used to calculate age-specific and serotype-specific incident rate ratios (IRRs) comparing pre (2002-2004) and post (2007-2009) universal childhood 7vPCV periods. RESULTS: Following the introduction of the 7vPCV program, the rate of IPD in children aged <2 years decreased by 81% for all serotypes (IRR 0.19, 95% CI, 0.13-0.28) and by 98% for 7vPCV serotypes (IRR 0.02, 95% CI, 0.007-0.07). At the same time, there was some evidence for an increase in IPD caused by 13vPCV specific serotypes (IRR 1.58, 95% CI, 0.78-3.21) and non-13vPCV serotypes (IRR 1.80, 95% CI, 0.45-7.21). Among adults aged ≥65 years, overall there was a 27% reduction in IPD caused by all serotypes following introduction of the 7vPCV program (IRR 0.73, 95% CI, 0.58-0.93). However, the rate of IPD increased in the last 2 years of the study period. The initial decrease was a result of a 74% reduction in the rate of IPD due to 7vPCV serotypes (IRR 0.26, 95% CI, 0.17-0.40). At the same time, the rate of IPD increased for 13vPCV specific serotypes (IRR 1.55, 95% CI, 0.94-2.54), 23vPPV specific serotypes (IRR 1.91, 95% CI, 0.99-3.71) and particularly non-23vPPV serotypes (IRR 5.3, 95% CI, 1.83-15.34). CONCLUSION: There has been a large direct and sustained benefit from the universal 7vPCV program in children, particularly those aged <2 years, with some evidence for serotype replacement. There is also good evidence that the childhood program has provided indirect benefits to adults aged ≥65 years, although serotype replacement has reduced the initial benefits.

Outbreak of Salmonella typhimurium phage type 44 infection among attendees of a wedding reception, April 2009.

On 30 April 2009, the Communicable Disease Control Branch (CDCB) South Australia was notified of a Salmonella infection in a person who attended a wedding reception on 25 April 2009. Several other attendees reported becoming unwell with a similar gastrointestinal illness. The CDCB commenced an investigation to: characterise the outbreak in terms of person, place and time; identify probable source or sources; and implement control measures. A retrospective cohort study was undertaken among wedding reception attendees. A questionnaire collecting information on demographics, illness and menu items consumed was given to the majority of attendees. An environmental inspection of the wedding reception premise and food supplier premise, including food sampling was conducted to identify plausible sources of infection. The questionnaire response rate was 77%, from which an attack rate of 20% was calculated. There was a significant association between consumption of garlic aioli and illness (OR 5.4, 95% CI: 1.6, 18.1). Nine wedding reception attendees' stool samples tested positive for Salmonella Typhimurium phage type 44. A sample of garlic aioli also tested positive for Salmonella Typhimurium phage type 44. The ingredients of the garlic aioli included raw egg yolk, roasted garlic, Dijon mustard, vinegar and vegetable oil. The raw egg yolk was identified as a high risk food item; however no eggs tested positive for Salmonella.