4CMenB sustained vaccine effectiveness against invasive meningococcal B disease and gonorrhoea at three years post programme implementation.

OBJECTIVES: To evaluate persistence of vaccine effectiveness (VE) and vaccine impact (VI) on invasive meningococcal B (MenB) disease and gonorrhoea at three years after implementation of a state funded 4CMenB programme for infants, children, adolescents and young people in South Australia. METHODS: VI was assessed using a Poisson or negative binomial regression model, and VE was estimated using screening and case-control methods. Chlamydia controls were used to estimate VE in the primary analysis to control potential confounding effects such as high-risk sexual behaviour associated with sexually transmitted infections. RESULTS: During the three-year programme, reductions of 63.1% (95%CI 29.0-80.9%) and 78.5% (95%CI 33.0-93.1%) in incidence of MenB disease were observed in infants and adolescents, respectively. There were no cases in infants who had received three doses of 4CMenB. Two-dose VE against MenB disease was 90.7% (95%CI 6.9-99.1%) for the childhood programme and 83.5% (95%CI 0-98.2%) for the adolescent programme. Two-dose VE against gonorrhoea in adolescents was 33.2% (95%CI 15.9-47.0%). Lower VE estimates were demonstrated after 36 months post-vaccination (23.2% (95%CI 0-47.5%)> 36 months post-vaccination compared to 34.9% (95%CI 15.0-50.1%) within 6-36 months). Higher VE estimates were found after excluding patients with repeat gonorrhoea infections (37.3%, 95%CI 19.8-51.0%). For gonorrhoea cases co-infected with chlamydia VE was maintained (44.7% (95%CI 17.1-63.1%). CONCLUSION: The third-year evaluation results show persistent vaccine effectiveness of 4CMenB against MenB disease in infants and adolescents. As this is the first ongoing programme for adolescents, moderate vaccine protection against gonorrhoea with waning effectiveness three years post-vaccination was demonstrated in adolescents and young adults. The additional protection of 4CMenB vaccine against gonorrhoea, likely through cross-protection should be considered in cost-effectiveness analyses. A booster dose may need to be further evaluated and considered in adolescents due to waning protection against gonorrhoea demonstrated after 36 months post-vaccination.

Effectiveness and impact of the 4CMenB vaccine against invasive serogroup B meningococcal disease and gonorrhoea in an infant, child, and adolescent programme: an observational cohort and case-control study.

BACKGROUND: A programme of vaccination with the four-component serogroup B meningococcal (4CMenB) vaccine was introduced in South Australia for infants and children aged 0-3 years on Oct 1, 2018, and for senior school students in school years 10 and 11 (aged 15-16 years) and young adults aged 17-20 years on Feb 1, 2019. We aimed to evaluate vaccine effectiveness and impact on serogroup B meningococcal disease and gonorrhoea 2 years after implementation of the programme. METHODS: We did a cohort and case-control study among those targeted by the South Australia 4CMenB vaccination programme. We obtained disease notification data from SA Health, Government of South Australia, and vaccine coverage data from the South Australian records of the Australian Immunisation Register. Vaccine effectiveness was estimated as the reduction in the odds of infection using the screening and case-control methods. Vaccine impact was estimated as incidence rate ratios (IRRs), obtained by comparing case numbers in each year following the start of the vaccination programme with cases in the equivalent age cohort during the pre-vaccination programme years. We used Poisson or negative binomial models, as appropriate, with adjustment for changes in the incidence of serogroup B meningococcal disease in age cohorts not eligible for vaccination through the state programme. FINDINGS: 4CMenB vaccine coverage 2 years after introduction of the childhood vaccination programme was 94·9% (33 357 of 35 144 eligible individuals) for one dose, 91·4% (26 443 of 28 922) for two doses, and 79·4% (15 440 of 19 436) for three doses in infants. The one-dose (77·1%, 16 422 of 21 305) and two-dose (69·0%, 14 704 of 21 305) coverage was highest in adolescents born in 2003 (approximately year 10 students). 2 years after implementation of the childhood vaccination programme, incidence of serogroup B meningococcal disease was significantly reduced compared with before programme implementation in infants aged 12 weeks to 11 months (adjusted IRR [aIRR] 0·40 [95% CI 0·23-0·69], p=0·0011), but not in those aged 1 year (0·79 [0·16-3·87], p=0·77), 2 years (0·75 [0·18-3·14], p=0·70), or 4 years (3·00 [0·47-18·79], p=0·24). aIRRs were not calculable in those aged 3 or 5 years because of no cases occurring after programme implementation. aIRR for serogroup B meningococcal disease was 0·27 (0·06-1·16, p=0·078) in adolescents aged 15-18 years 2 years after implementation of the adolescent and young adult programme, and 1·20 (0·70-2·06, p=0·51) in those aged 19-21 years in the first year. Two-dose vaccine effectiveness against serogroup B meningococcal disease was estimated to be 94·2% (95% CI 36·6-99·5) using the screening method and 94·7% (40·3-99·5) using the case-control method in children, and 100% in adolescents and young adults (no cases reported after implementation). Estimated two-dose vaccine effectiveness against gonorrhoea in adolescents and young adults was 32·7% (8·3-50·6) based on the case-control method using age-matched individuals with chlamydia infection as controls. INTERPRETATION: 4CMenB vaccine shows sustained effectiveness against serogroup B meningococcal disease 2 years after introduction in infants and adolescents, and moderate effectiveness against gonorrhoea in adolescents. The high vaccine effectiveness against serogroup B meningococcal disease is likely due to high coverage in the target age groups and close antigenic match between the 4CMenB vaccine and the disease-associated serogroup B meningococcal strains circulating in South Australia. COVID-19-related physical distancing policies might have contributed to further declines in serogroup B meningococcal disease cases during the programme's second year. FUNDING: SA Health, Government of South Australia.

Whole-Genome Sequencing of SARS-CoV-2 from Quarantine Hotel Outbreak.

Hotel quarantine for international travelers has been used to prevent coronavirus disease spread into Australia. A quarantine hotel-associated community outbreak was detected in South Australia. Real-time genomic sequencing enabled rapid confirmation tracking the outbreak to a recently returned traveler and linked 2 cases of infection in travelers at the same facility.

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.

An outbreak and case-control study of Salmonella Havana linked to alfalfa sprouts in South Australia, 2018.

An epidemiological investigation and a retrospective case-control study were conducted into an outbreak of Salmonella Havana in alfalfa sprouts, in Adelaide, Australia. In total, 31 cases of S. Havana were notified during June and July 2018 and linked to the outbreak. Eighteen cases and 54 unmatched controls were included in a case-control study. Results from the case-control study indicated an increased risk of illness linked to the consumption of alfalfa sprouts; this was supported by trace-back, sampling and environmental investigations. This outbreak of S. Havana was caused by consumption of alfalfa sprouts from one local sprouts producer. It is unclear as to when in the production of alfalfa sprouts the contamination occurred. However, contaminated seeds and poor pest control are the most likely causes. This investigation highlights the importance of ensuring that producers take appropriate action to minimise the likelihood of contamination and to comply with legislation and standards for primary production and food safety.

Experimental and theoretical insights into the mechanisms of sulfate and sulfamate ester hydrolysis and the end products of type I sulfatase inactivation by aryl sulfamates.

Type I sulfatases catalyze the hydrolysis of sulfate esters through S-O bond cleavage and possess a catalytically essential formylglycine (FGly) active-site residue that is post-translationally derived from either cysteine or serine. Type I sulfatases are inactivated by aryl sulfamates in a time-dependent, irreversible, and active-site directed manner consistent with covalent modification of the active site. We report a theoretical (SCS-MP2//B3LYP) and experimental study of the uncatalyzed and enzyme-catalyzed hydrolysis of aryl sulfates and sulfamates. In solution, aryl sulfate monoanions undergo hydrolysis by an S(N)2 mechanism whereas aryl sulfamate monoanions follow an S(N)1 pathway with SO2NH as an intermediate; theory traces this difference to the markedly greater stability of SO2NH versus SO3. For Pseudomonas aeruginosa arylsulfatase-catalyzed aryl sulfate hydrolysis, Brønsted analysis (log(V(max)/K(M)) versus leaving group pK(a) value) reveals ß(LG) = -0.86 ± 0.23, consistent with an S(N)2 at sulfur reaction but substantially smaller than that reported for uncatalyzed hydrolysis (ß(LG) = -1.81). Common to all proposed mechanisms of sulfatase catalysis is a sulfated FGly intermediate. Theory indicates a ≥26 kcal/mol preference for the intermediate to release HSO4(-) by an E2 mechanism, rather than alkaline phosphatase-like S(N)2 substitution by water. An evaluation of the stabilities of various proposed end-products of sulfamate-induced sulfatase inactivation highlights that an imine N-sulfate derived from FGly is the most likely irreversible adduct.

'Surprise': Outbreak of Campylobacter infection associated with chicken liver pâté at a surprise birthday party, Adelaide, Australia, 2012.

OBJECTIVE: In July 2012, an outbreak of Campylobacter infection was investigated by the South Australian Communicable Disease Control Branch and Food Policy and Programs Branch. The initial notification identified illness at a surprise birthday party held at a restaurant on 14 July 2012. The objective of the investigation was to identify the potential source of infection and institute appropriate intervention strategies to prevent further illness. METHODS: A guest list was obtained and a retrospective cohort study undertaken. A combination of paper-based and telephone questionnaires were used to collect exposure and outcome information. An environmental investigation was conducted by Food Policy and Programs Branch at the implicated premises. RESULTS: All 57 guests completed the questionnaire (100% response rate), and 15 met the case definition. Analysis showed a significant association between illness and consumption of chicken liver pâté (relative risk: 16.7, 95% confidence interval: 2.4-118.6). No other food or beverage served at the party was associated with illness. Three guests submitted stool samples; all were positive for Campylobacter. The environmental investigation identified that the cooking process used in the preparation of chicken liver pâté may have been inconsistent, resulting in some portions not cooked adequately to inactivate potential Campylobacter contamination. DISCUSSION: Chicken liver products are a known source of Campylobacter infection; therefore, education of food handlers remains a high priority. To better identify outbreaks among the large number of Campylobacter notifications, routine typing of Campylobacter isolates is recommended.

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.

Direct evidence for ArO-S bond cleavage upon inactivation of Pseudomonas aeruginosa arylsulfatase by aryl sulfamates.

Pseudomonas aeruginosa arylsulfatase catalyses the cleavage of aryl sulfates and is an excellent model for human estrone sulfatase, which is implicated in hormone-dependent breast cancer. Aryl sulfamates are inactivators of sulfatases; however, little is known about their mechanism. We studied the inactivation of Pseudomonas aeruginosa arylsulfatase A by a range of aryl sulfamates, including the clinical agent 667COUMATE (STX64) used to inactivate estrone sulfatase. Inactivation was time dependent, irreversible, and active-site directed, consistent with a covalent modification at the active site. In terms of the kinetic parameters of inactivation k(inact) and K(i), K(i) values are in the micromolar to nanomolar range, and the inactivation half-life is less than 30 s. A Brønsted plot of k(inact)/K(i) has a steep slope (beta(lg) = -1.1), which implies that the transition state for the first irreversible chemical step of inactivation involves a high degree of charge transfer and cleavage of the ArO-S bond. Detection of the released phenol and titration of the residual activity showed the stoichiometry of inactivation to be in the range 3-6, with the greatest values found for the most effective inactivators. Thus, multiple sulfamoylation events appear to occur during the inactivation process. These data provide valuable insight into the mechanism of sulfatase inactivation by sulfamates.

Electronic structure of the sulfonyl and phosphonyl groups: a computational and crystallographic study.

A computational and X-ray crystallographic investigation of the electronic and geometric structures of a range of sulfonyl (-SO(2)-) and phosphonyl (-PO(2)--) containing species was undertaken to investigate the nature of valency and bonding in these functional groups. The traditional representation of sulfonyl and phosphonyl species is with octet-violating Lewis structures, which require d-orbital participation at the central atom. However, computational studies cast serious doubt upon this bonding model. In this work, we have employed NBO/NRT analysis to investigate hybridization, atomic formal charges, donor-acceptor interactions, and resonance structure contributions. Our results predict that within sulfonyl and phosphonyl systems, bonding interactions are highly polarized, of the form X+-Y- (X = P, S), and possess additional contributions from reciprocal n --> sigma* interactions where substituents off sulfur or phosphorus simultaneously act as donors and acceptors. Experimental evidence for the proposed bonding arrangement is provided for the sulfonyl functional group through a series of low-temperature X-ray structure correlations for sulfate monoesters, sulfamates, and methanesulfonates. Examination of changes to bond lengths and geometries upon substituent variation support the computational results. Together, our studies lend support for a bonding network in sulfonyl and phosphonyl groups composed of polar interactions augmented with reciprocal hyperconjugative bonding, which does not necessitate significant d-orbital participation nor formal octet violation at the central sulfur or phosphorus.

Ground state structures of sulfate monoesters and sulfamates reveal similar reaction coordinates for sulfuryl and sulfamyl transfer.

Structure/reactivity and structure/structure correlations of 5 sulfate monoesters and 11 sulfamate esters determined by low temperature X-ray crystallography reveal similar ground state deformations that suggest similar reaction coordinates for sulfuryl and sulfamyl group transfer.