The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, and that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections.This observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4-7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison.The protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.

In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations.In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size.In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation.ClinicalTrials.gov NCT01735084 and NCT01174849.

The Northern Territory (NT) is a geographically remote region of northern and central Australia. Approximately a third of the population are First Nations Australians, many of whom live in remote regions. Due to the physical environment and climate, and scale of social inequity, the rates of many infectious diseases are the highest nationally. Molecular typing and genomic sequencing in research and public health have provided considerable new knowledge on the epidemiology of infectious diseases in the NT. We review the applications of genomic sequencing technology for molecular typing, identification of transmission clusters, phylogenomics, antimicrobial resistance prediction, and pathogen detection. We provide examples where these methodologies have been applied to infectious diseases in the NT and discuss the next steps in public health implementation of this technology.

BACKGROUND: The global distribution of melioidosis is under considerable scrutiny, with both unmasking of endemic disease in African and Pacific nations and evidence of more recent dispersal in the Americas. Because of the high incidence of disease in tropical northern Australia, The Darwin Prospective Melioidosis Study commenced in October, 1989. We present epidemiology, clinical features, outcomes, and bacterial genomics from this 30-year study, highlighting changes in the past decade. METHODS: The present study was a prospective analysis of epidemiological, clinical, and laboratory data for all culture-confirmed melioidosis cases from the tropical Northern Territory of Australia from Oct 1, 1989, until Sept 30, 2019. Cases were identified on the basis of culture-confirmed melioidosis, a laboratory-notifiable disease in the Northern Territory of Australia. Patients who were culture-positive were included in the study. Multivariable analysis determined predictors of clinical presentations and outcome. Incidence, survival, and cluster analyses were facilitated by population and rainfall data and genotyping of Burkholderia pseudomallei, including multilocus sequence typing and whole-genome sequencing. FINDINGS: There were 1148 individuals with culture-confirmed melioidosis, of whom 133 (12%) died. Median age was 50 years (IQR 38-60), 48 (4%) study participants were children younger than 15 years of age, 721 (63%) were male individuals, and 600 (52%) Indigenous Australians. All but 186 (16%) had clinical risk factors, 513 (45%) had diabetes, and 455 (40%) hazardous alcohol use. Only three (2%) of 133 fatalities had no identified risk. Pneumonia was the most common presentation occurring in 595 (52%) patients. Bacteraemia occurred in 633 (56%) of 1135 patients, septic shock in 240 (21%) patients, and 180 (16%) patients required mechanical ventilation. Cases correlated with rainfall, with 80% of infections occurring during the wet season (November to April). Median annual incidence was 20·5 cases per 100 000 people; the highest annual incidence in Indigenous Australians was 103·6 per 100 000 in 2011-12. Over the 30 years, annual incidences increased, as did the proportion of patients with diabetes, although mortality decreased to 17 (6%) of 278 patients over the past 5 years. Genotyping of B pseudomallei confirmed case clusters linked to environmental sources and defined evolving and new sequence types. INTERPRETATION: Melioidosis is an opportunistic infection with a diverse spectrum of clinical presentations and severity. With early diagnosis, specific antimicrobial therapy, and state-of-the-art intensive care, mortality can be reduced to less than 10%. However, mortality remains much higher in the many endemic regions where health resources remain scarce. Genotyping of B pseudomallei informs evolving local and global epidemiology. FUNDING: The Australian National Health and Medical Research Council.

To document the burden of disease caused by an outbreak of rotavirus (RV) gastroenteritis in a remote Aboriginal community. During an outbreak of RV gastroenteritis, data were collected from patients notes, hospital and laboratory data. Age, date of presentation, severity of illness, number of total presentations, presentations per patient, total clinic hours per presentation, stool analysis, treatment and outcomes were measured. These data were compared with a time period of equal duration in order to establish a baseline burden of gastroenteritis. In a remote Aboriginal community 26 patients were managed for acute diarrhoea between 19 September 2005 and 5 October 2005. Gastroenteritis was the diagnosis in 24 cases for which there were 55 presentations. Stool specimens were analysed in 14 (58%) cases. RV was identified in eight (57%) of these specimens. The majority (80%) had mild disease. Moderate disease was noted in 15% and 5% were follow-up reviews. There were no severe cases of gastroenteritis. Four patients required evacuation to hospital. From a total of 607 presentations to the clinic during this time period, 55 (9%) were managed for acute diarrhoea. In the comparative time period there were five (0.9%) cases of acute diarrhoea from a total of 571 presentations. Rotavirus gastroenteritis places a large burden on remote Aboriginal communities and health-care centres in the form of morbidity, overworked clinic staff, economic cost and reduced capacity for primary health-care duties.

It is recommended that infants born to women with hepatitis B infection should have serological review following completion of a four dose vaccination schedule. A review was undertaken on 102 neonates who received hepatitis B immunoglobulin to ascertain the proportion that were fully immunised and then followed up. Of the 66 infants for whom data were available, 65 (98.5%) had appropriately received four doses of hepatitis B vaccine in infancy and a further child had received three doses. Only 19/66 (29%; 95%CI: 18-41%) infants had documented follow-up serology results, one of whom was infected and one of whom was immune through clearance of infection. All children who had no serology documented were traced and offered testing in primary care. Our results demonstrate that although adherence to the vaccination schedule in this group of infants was good, mechanisms for ensuring that infants receive serology testing need to be strengthened.

Centre for Disease Control, Public Health Unit, Top End Health Service, Northern Territory Government Department of Health, Darwin, Northern Territory, Australia.

OBJECTIVE: To determine the level of immunity to hepatitis A virus infection in rural Australian Aboriginal populations in the "Top End" of the Northern Territory. METHODS: A total of 344 sera, for which details of donors' age, sex and domicile were available, were collected and tested for hepatitis A total antibody in a delinked seroprevalence study. RESULTS: Overall, 337/344 samples (97.97%) tested positive for hepatitis A total antibodies--18/20 samples (90%) in the 1-5 year age group; 85/88 (96.6%) in the 6-10 year age group; 98/98 (100%) in the 11-15 year age group; 32/33 (97.0%) in the 16-20 year age group and 104/105 (99%) in the older than 20 year age group. CONCLUSION: Hepatitis A is hyperendemic in the rural Aboriginal communities studied and the virus is acquired predominantly in the first five years of life. Symptomatic hepatitis A infection is uncommon in this population. We suggest that hepatitis A vaccination for rural Aboriginal children is not indicated as it would not reduce clinical disease rates and may produce a cohort whose immunity could decrease over the following 10 years. Although vaccination is appropriate for non-immune individuals working in remote communities, emphasis must be placed on the inequities in health infrastructure and education underlying the high transmission rates in Aboriginal children.

Leptospirosis is a worldwide zoonotic waterborne disease endemic in tropical and subtropical climates. Outbreaks have been observed in the Northern Territory (NT) of Australia. We briefly described the epidemiology of leptospirosis in the NT between 2012 and 2022, and undertook an investigation of a cluster of three leptospirosis cases observed in crocodile workers between January and December 2022 in the Top End of the NT. A descriptive case series was conducted to investigate the cluster; all three cases were male and non-Aboriginal with a median age of 46.5 years; none took chemoprophylaxis; only one of the three cases reported wearing appropriate protective attire; all reported receiving limited to no education about personal protective measures from their associated workplaces. Higher than average rainfall in both February and December 2022 likely contributed to the increased risk of infection in those months. Changing climate patterns are likely to result in more frequent periods of heavy rain, and risk of contracting leptospirosis in the NT may increase, particularly for those who work in wet and muddy conditions. Promoting the use of protective workplace clothing and equipment, the use of waterproof dressings for skin abrasions, regular hand hygiene, and the consideration of chemoprophylaxis in certain circumstances may prevent future cases.