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.Helen S. Marshall, Prabha H. Andraweera, Bing Wang, Mark McMillan, Ann P. Koehler, Noel Lally ... et al

Maternal metabolic factors and the association with gestational diabetes: a systematic review and meta-analysis

First published: 14 April 2022Gestational diabetes (GDM) is associated with several adverse outcomes for the mother and child. Higher levels of individual lipids associate with risk of GDM, and metabolic syndrome, a clustering of risk factors also increases risk for GDM. Metabolic factors can be modified by diet and lifestyle. This review comprehensively evaluates the association between metabolic syndrome and its components, measured in early pregnancy, and risk for GDM. Databases (CINAHL, PubMed, Embase, and Cochrane Library) were searched from inception to 5 May 2021. Eligible studies included ≥1 metabolic factor (waist circumference, blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol, measured at 2 . Data were pooled by random-effects models and expressed as odds ratio and 95% confidence intervals. Of 7213 articles identified, 40 unique articles were included in meta-analysis. In analyses adjusting for maternal age and body mass index, GDM was increased with increasing fasting plasma glucose (OR 1.92; 95% CI 1.39-2.64, k=7 studies) or having metabolic syndrome (OR 2.52; 1.65, 3.84, k=3). Women with overweight (OR 2.17; 95% CI 1.89, 2.50, k=12) or obesity (OR 4.34; 95% CI 2.79-6.74, k=9) also were at increased risk for GDM. Early pregnancy assessment of glucose or the metabolic syndrome, offers a potential opportunity to detect and treat individual risk factors as an approach toward GDM prevention; weight loss for pregnant women with overweight or obesity is not recommended. This article is protected by copyright. All rights reserved.Nahal Habibi, Aya Mousa, Chau Thien Tay, Mahnaz Bahri Khomami, Thiannon K. Patten, Prabha H. Andraweera, Molla Wassie, Jared Vandersluys, Ali Aflatounian, Tina Bianco-Miotti, Shao J. Zhou, Jessica A. Griege

A case series of five Sri Lankan patients with ovotesticular disorder of sex development

Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation in which the gonads of an individual are characterized by the presence of both mature ovarian and testicular tissues. The objective of this paper is to report the clinical, cytogenetic and histopathological findings in Sri Lankan patients diagnosed with OT-DSD who were referred to the Human Genetics Unit for cytogenetic evaluation during 2005 to 2011. Five patients had histopathologically confirmed OT-DSD. Their ages at presentation ranged from 2 mo to 47 yr. Clinical symptoms varied from ambiguous genitalia and inguinal hernias at birth to a lower abdominal mass presenting in adulthood. All 5 were reared as phenotypic males. An ovotestis was detected in all cases except one, and the predominant karyotype was 46,XY. The findings in this series of predominantly 46,XY karyotype are in contrast to previously published reports that have reported 46,XX as being the predominant karyotype. It is therefore recommended that individuals with ambiguous genitalia who have the 46,XY karyotype should be thoroughly investigated by ultrasonographic or laparoscopic assessment to determine the exact nature of their internal genital organs. OT-DSD should also be considered in the differential diagnosis of patients with cryptorchidism and inguinal hernia.Kalum T. Wettasinghe, Nirmala D. Sirisena, Prabha H. Andraweera, Rohan W. Jayasekara, Vajira H. W. Dissanayak

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.Bing Wang, Lynne Giles, Prabha Andraweera, Mark McMillan, Sara Almond, Rebecca Beazley, Janine Mitchell, Noel Lally, Michele Ahoure, Emma Denehy, Ann Koehler, Louise Flood, Helen Marshal

Randomised controlled trials of behavioural nudges delivered through text messages to increase influenza and COVID-19 vaccines among pregnant women (the EPIC study): study protocol

Published online: 12 July 2023BACKGROUND: Influenza and COVID-19 infections during pregnancy may have serious adverse consequences for women as well as their infants. However, uptake of influenza and COVID-19 vaccines during pregnancy remains suboptimal. This study aims to assess the effectiveness of a multi-component nudge intervention to improve influenza and COVID-19 vaccine uptake among pregnant women. METHODS: Pregnant women who receive antenatal care at five tertiary hospitals in South Australia, Western Australia and Victoria will be recruited to two separate randomised controlled trials (RCTs). Women will be eligible for the COVID-19 RCT is they have received two or less doses of a COVID-19 vaccine. Women will be eligible for the influenza RCT if they have not received the 2023 seasonal influenza vaccine. Vaccination status at all stages of the trial will be confirmed by the Australian Immunisation Register (AIR). Participants will be randomised (1:1) to standard care or intervention group (n = 1038 for each RCT). The nudge intervention in each RCT will comprise three SMS text message reminders with links to short educational videos from obstetricians, pregnant women and midwives and vaccine safety information. The primary outcome is at least one dose of a COVID-19 or influenza vaccine during pregnancy, as applicable. Logistic regression will compare the proportion vaccinated between groups. The effect of treatment will be described using odds ratio with a 95% CI. DISCUSSION: Behavioural nudges that facilitate individual choices within a complex context have been successfully used in other disciplines to stir preferred behaviour towards better health choices. If our text-based nudges prove to be successful in improving influenza and COVID-19 vaccine uptake among pregnant women, they can easily be implemented at a national level. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05613751. Registered on November 14, 2022.Prabha H. Andraweera, Bing Wang, Margie Danchin, Christopher Blyth, Ivo Vlaev, Jason Ong, Jodie Dodd, Jennifer Couper, Thomas R. Sullivan, Jonathan Karnon, Nicola Spurrier, Michael Cusack, Dylan Mordaunt, Dimi Simatos, Gus Dekker, Samantha Carlson, Jane Tuckerman, Nicholas Wood, Lisa Whop and Helen S. Marshal