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Australian First Nations children are at very high risk of early, recurrent, and persistent bacterial otitis media and respiratory tract infection. With the PREVIX randomised controlled trials, we aimed to evaluate the immunogenicity of novel pneumococcal conjugate vaccine (PCV) schedules.PREVIX_BOOST was a parallel, open-label, outcome-assessor-blinded, randomised controlled trial. Aboriginal children living in remote communities of the Northern Territory of Australia were eligible if they had previously completed the three-arm PREVIX_COMBO randomised controlled trial of the following vaccine schedules: three doses of a 13-valent PCV (PCV13; PPP) or a ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10; SSS) given at 2, 4, and 6 months, or SSS given at 1, 2, and 4 months followed by PCV13 at 6 months (SSSP). At age 12 months, eligible children were randomly assigned by a computer-generated random sequence (1:1, stratified by primary group allocation) to receive either a PCV13 booster or a PHiD-CV10 booster. Analyses used intention-to-treat principles. Co-primary outcomes were immunogenicity against protein D and serotypes 3, 6A, and 19A. Immunogenicity measures were geometric mean concentrations (GMC) and proportion of children with IgG concentrations of 0·35 μg/mL or higher (threshold for invasive pneumococcal disease), and GMCs and proportion of children with antibody levels of 100 EU/mL or higher against protein D. Standardised assessments of otitis media, hearing impairment, nasopharyngeal carriage, and developmental outcomes are reported. These trials are registered with ClinicalTrials.gov (NCT01735084 and NCT01174849).Between April 10, 2013, and Sept 4, 2018, 261 children were randomly allocated to receive a PCV13 booster (n=131) or PHiD-CV10 booster (n=130). Adequate serum samples for pneumococcal serology were obtained from 127 (95%) children in the PCV13 booster group and 126 (97%) in the PHiD-CV10 booster group; for protein D, adequate samples were obtained from 126 (96%) children in the PCV13 booster group and 123 (95%) in the PHiD-CV10 booster group. The proportions of children with IgG concentrations above standard thresholds in PCV13 booster versus PHiD-CV10 booster groups were the following: 71 (56%) of 126 versus 81 (66%) of 123 against protein D (difference 10%, 95% CI -2 to 22), 85 (67%) of 127 versus 59 (47%) of 126 against serotype 3 (-20%, -32 to -8), 119 (94%) of 127 versus 91 (72%) of 126 against serotype 6A (-22%, -31 to -13), and 116 (91%) of 127 versus 108 (86%) of 126 against serotype 19A (-5%, -13 to 3). Infant PCV13 priming mitigated differences between PCV13 and PHiD-CV10 boosters. In both groups, we observed a high prevalence of otitis media (about 90%), hearing impairment (about 75%), nasopharyngeal carriage of pneumococcus (about 66%), and non-typeable H influenzae (about 57%). Of 66 serious adverse events, none were vaccine related.Low antibody concentrations 6 months post-booster might indicate increased risk of pneumococcal infection. The preferred booster was PCV13 if priming did not have PCV13, otherwise either PCV13 or PHiD-CV10 boosters provided similar immunogenicity. Mixed schedules offer flexibility to regional priorities. Non-PCV13 serotypes and non-typeable H influenzae continue to cause substantial disease and disability in Australian First Nation's children.National Health and Medical Research Council (NHMRC).

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.

Background Hepatitis B virus (HBV) vaccination in the Northern Territory (NT) was funded for all Aboriginal and Torres Strait Islander newborns in 1988 and for all newborns in 1990. The prevalence of HBV in the Northern Territory was found to be higher in Aboriginal and Torres Strait Islander women than in non-Indigenous women across 2005–2010. We examined more recent data to assess whether the gap remains. Methods We linked data from two routinely collected registries, the NT Perinatal Register and the NT Notifiable Diseases System, to investigate the prevalence of HBV infection, according to eligibility for infant HBV vaccination, in women giving birth during 2005–2015. Results There were 22,781 women recorded as giving birth in public hospitals in the Northern Territory during 2005–2015. Hepatitis B virus prevalence was highest in Aboriginal and Torres Strait Islander (1.8%) and overseas-born women (1.8%). Among Aboriginal and Torres Strait Islander women, estimated hepatitis B virus prevalence was significantly higher in those born before the implementation of the vaccination program than in those born afterwards (2.4% versus 0.3%). Prevalence was highest amongst those living in very remote areas, both overall (2.2%) and within the birth cohort eligible for HBV vaccination. Conclusions Hepatitis B virus prevalence in Northern Territory Aboriginal and Torres Strait Islander women appears to be declining as more individuals vaccinated as part of infant vaccination programs reach adulthood. Prevalence remains highest in remote areas, highlighting the importance of ongoing monitoring and of promoting vaccination in these regions.

Background Universal pneumococcal conjugate vaccine (PCV) programs began in Indigenous Australian children in 2001 and all children in 2005, changing to 13-valent PCV (PCV13) in 2011. We used laboratory data for invasive pneumococcal disease (IPD) and coded hospitalizations for noninvasive pneumococcal community-acquired pneumonia (PnCAP) to evaluate long-term impact. Methods Annual incidence (per 100 000 population) was calculated for age-specific total IPD, PCV13 non–7-valent PCV (PCV7) serotypes, and PnCAP by Indigenous status. Incidence in the pre–universal PCV7 (2002–2004), early PCV7 (2005–2007), pre-PCV13 (2008 to mid-2011), and post-PCV13 (mid-2011 to 2016) periods was used to calculate incidence rate ratios (IRRs). Results In the total population, all-age incidence of IPD declined from 11.8 pre-PCV7 to 7.1 post-PCV13 (IRR, 0.61 [95% confidence interval {CI}, .59–.63]) but for PnCAP declined among ages Conclusions Fifteen years post-PCV and 5 years post-PCV13, direct and indirect impact on IPD and PnCAP differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings. Fifteen years after pneumococcal conjugate vaccine (PCV) introduction and 5 years post-PCV13, direct and indirect impact on invasive pneumococcal disease and pneumococcal community-acquired pneumonia differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings.

Objectives: We report a cluster of acute rheumatic fever (ARF) cases and the public health response in a high‐burden Australian setting. Methods: The public health unit was notified of an increase in ARF cases in a remote Australian Aboriginal community. A multi‐disciplinary group coordinated the response. Household contacts were screened for ARF or group A Streptococcus (GAS) infection by questionnaire and swab collection, offered an echocardiogram if aged 5–20 years, and intramuscular benzathine benzylpenicillin if aged over one year or if less than one year with impetigo. Results: Fifteen definite and seven probable ARF cases were diagnosed in the community in July–December 2014 (all‐age incidence of definite ARF: 1,473/100,000). The public health response identified two additional cases of ARF. A total of 81 contacts were screened; GAS was detected in 3/76 (4%) throat swabs and 11/24 (46%) skin swabs. Molecular typing revealed high GAS strain diversity. Conclusions: The incidence of ARF during this cluster was very high. Carriage and infection with GAS was observed, but no outbreak strain identified. Implications for public health: A national public health guideline has since been developed that includes advice on the investigation of an ARF outbreak/cluster. Sustained efforts with strong community engagement are required to tackle high ARF rates.

Acute post-streptococcal glomerulonephritis (APSGN) is an inflammatory kidney disease following infection with nephritogenic strains of Group A Streptococcus. In 1991, APSGN became notifiable in the Northern Territory (NT) of Australia with cases recorded on the NT Notifiable Disease Database (NTNDS). The case definition of a confirmed case requires laboratory definitive evidence or laboratory suggestive evidence in conjunction with a clinically compatible illness. Probable cases require clinical evidence only. Acute post-streptococcal glomerulonephritis notifications from 2009 to 2016 were extracted from the NTNDS. Of the 322 cases, 261 were confirmed and 61 probable. The majority, 304 (94%), were Aboriginal and the median age was 8 years (range: 0–62 years). Incidence for confirmed cases was 13.8/100,000 person-years, with inclusion of probable cases increasing incidence to 17.0/100,000 person-years. Highest incidence of confirmed cases was in Aboriginal children less than 15 years of age at 124.0 cases/100,000 person-years. The rate ratio of confirmed cases in Aboriginal to non-Aboriginal Australians was 18.9 (95% confidence interval: 11.4–33.6). Recent trends show a consistently high number of notifications annually with less frequent outbreaks. The Aboriginal population of the NT continues to have high rates of APSGN with recent trends showing higher rates than previously reported. Sustained preventative efforts and continued surveillance strategies are needed.

Strict physical distancing measures and border controls have been introduced in the Northern Territory (NT), and across Australia, to reduce the spread of coronavirus disease 2019 (COVID-19). These measures have been associated with reduced incidence of other respiratory illnesses such as influenza. It is currently unclear what effect these measures have on non-respiratory communicable diseases. The incidence of notifiable non-respiratory communicable diseases within the NT, from 15 March to 15 May 2020, the period of most restrictive physical distancing, was monitored and is here compared with two control periods: (i) the 4 months immediately prior and (ii) the same two-month period from the preceding 5 years. During the study period, there was a decline in incidence of communicable enteric illnesses, particularly in shigellosis and rotavirus where person-to-person spread is the main transmission route. There was an increase in chlamydial conjunctivitis in areas with endemic trachoma, which is under further investigation. There was no observed increase in conditions associated with crowding, such as those related to group A streptococcal infection.

Between 2010 and 2013, an outbreak of serotype-1 sequence type 306 (ST306) invasive pneumococcal disease (IPD) occurred primarily in remote locations of Northern and Central Australia. This is a descriptive study of the epidemiology of the outbreak using nationwide IPD surveillance data, supplemented with more detailed data held by affected jurisdictions, and of the response to the outbreak, including vaccination strategies. In the year the outbreak peaked (2011), serotype-1 IPD incidence was over 30-fold higher in the affected regions than in the rest of Australia (incidence rate ratio: 30.7 [95% CI 20.1–48.9]). The study includes 245 cases of serotype-1 IPD from the outbreak regions, with 75.5% identified as Indigenous. No reported cases of serotype-1 IPD occurred in young children who had completed either a 10- or 13-valent pneumococcal conjugate vaccine schedule. However serotype-1 IPD did occur in older children who had previously received 23-valent pneumococcal polysaccharide vaccine. Development of public-health-focused national IPD management guidelines, including suitable vaccine strategies for consistent use nationwide, could potentially decrease the duration and intensity of similar outbreaks in the future.

The Northern Territory (NT) Centre for Disease Control (CDC) undertook contact tracing of all notified cases of coronavirus disease 2019 (COVID-19) within the Territory. There were 28 cases of COVID-19 notified in the NT between 1 March and 30 April 2020. In total 527 people were identified as close contacts over the same period; 493 were successfully contacted; 445 were located in the NT and were subsequently quarantined and monitored for disease symptoms daily for 14 days after contact with a confirmed COVID-19 case. Of these 445 close contacts, 4 tested positive for COVID-19 after developing symptoms; 2/46 contacts who were cruise ship passengers (4.3%, 95% CI 0.5–14.8%) and 2/51 household contacts (3.9%, 95% CI 0.5–13.5%). None of the 326 aircraft passengers or 4 healthcare workers who were being monitored in the NT as close contacts became cases.

IntroductionStreptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are major otitis media pathogens that densely co-colonise the nasopharynx and infect the middle ear of Australian Aboriginal infants from very early in life. Our co-primary hypotheses are that at 18 months of age infants receiving 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) compared with those receiving 13-valent pneumococcal conjugate vaccine (PCV13) as a booster at 12 months of age will have higher antibody levels to Haemophilus influenzae protein D and that infants receiving PCV13 will have higher antibody levels to PCV13-only serotypes 3, 6A and 19A.Methods and analysesOur randomised controlled trial will enrol 270 Aboriginal children at 12 months of age to a booster dose of either PHiD-CV10 or PCV13. Children who completed the three-dose primary course schedules of PHiD-CV10 at 2, 4, 6 months of age; PCV13 at 2, 4, 6 months of age; or a combination schedule of PHiD-CV10 at 1, 2, 4 months of age plus PCV13 at 6 months of age are eligible. The co-primary assessor-blinded outcomes when the infants are 18 months of age are as follows: (a) IgG geometric mean concentration (GMC) and proportion with IgG ≥100 EU/mL for protein D, and (b) IgG GMC and the proportion with IgG ≥0.35 µg/mL for pneumococcal serotypes 3, 6A and 19A. Secondary immunogenicity comparisons of six primary and booster dose schedules of 10 shared serotypes at 18 months of age, nasopharyngeal carriage, all forms of otitis media, hearing loss and developmental milestones at 18, 24, 30 and 36 months of age will be reported.Ethics and disseminationEthics committees of NT Department of Health, Menzies, WA Department of Health and WA Aboriginal Health approved the study. Results will be presented to communities, at conferences and published in peer-reviewed journals.Trial registration numberNCT01735084.

The Northern Territory (NT) of Australia is currently free of the dengue mosquito Aedes (Stegomyia) aegypti (L). However, on 17 February 2004, two Ae. aegypti adults were captured in two routine CO2 -baited encephalitis virus surveillance traps in Tennant Creek, located 990 km south of Darwin in the NT. The detection triggered an immediate survey and control response undertaken by the NT Department of Health and Community Services, followed by a Commonwealth of Australia-funded Ae. aegypti elimination program. This report details the methods and results of the detection and subsequent elimination activities that were carried out between 2004 and 2006, returning the NT to its dengue vector-free status. There have been very few successful Ae. aegypti elimination programs in the world. This purposeful mosquito elimination for Australia was officially declared on 5 April 2006.

Since 2008, the Northern Territory (NT) Guidelines recommended delivering dTpa vaccine to postnatal women and all other household and close infant contacts. We aim to determine whether this pertussis cocooning strategy reduced infections in young infants in the NT. Infants

Background: The Northern Territory (NT) has the highest tuberculosis (TB) rate of all Australian jurisdictions. We combined TB public health surveillance data with genomic sequencing of Mycobacterium tuberculosis isolates in the tropical ‘Top End’ of the NT to investigate trends in TB incidence and transmission. Methods: This retrospective observational study included all 741 culture-confirmed cases of TB in the Top End over three decades from 1989–2020. All 497 available M. tuberculosis isolates were sequenced. We used contact tracing data to define a threshold pairwise SNP distance for hierarchical single linkage clustering, and examined putative transmission clusters in the context of epidemiologic information. Findings: There were 359 (48%) cases born overseas, 329 (44%) cases among Australian First Nations peoples, and 52 (7%) cases were Australian-born and non-Indigenous. The annual incidence in First Nations peoples from 1989-2019 fell from average 50.4 to 11.0 per 100,000 (P

The "Top End" of Australia is presently experiencing a gonorrhea epidemic. Gonococcal infection is usually limited to mucosal tissues but can lead to disseminated gonococcal infection (DGI), joint destruction, and severe sepsis. This study aimed to explore the epidemiology, presentation, management, and health-care impact of DGI in the Top End of the Northern Territory. Health records of patients diagnosed with proven, probable, or possible DGI between January 2010 and September 2018 were analyzed retrospectively. One hundred six cases of DGI were identified. Ninety-four patients (88.7%) were Indigenous Australian. The incidence of proven and probable DGI in the Indigenous population was 27.1 per 100,000 person-years, compared with 7.1 in the Top End population overall. Of 7,540 laboratory-proven gonococcal notifications, 1.3% (n = 97) were complicated by DGI. The highest incidence was in the 15-19-year age-group. Thirteen cases (12.3%) occurred in patients younger than 15 years. High rates of comorbid alcohol misuse, diabetes, systemic lupus erythematosus, rheumatic fever, and complement deficiency were observed. The "classic triad" of tenosynovitis, dermatitis, and polyarthralgia was rare. Ninety-four patients (88.7%) presented with purulent arthritis. Disseminated gonococcal infection was estimated to cause at least 10.0% of nonpenetrating septic arthritis in the Top End and 1,234 days of hospitalization during the study period. DGI is an important cause of morbidity in the Top End, particularly in the young, remote Indigenous Australian population. Clinical presentation varies from classical teaching. Urgent action in the health and community sector is required, particularly for at-risk populations, to prevent further debilitating and costly complications of gonococcal infection.

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.

Objective To describe the epidemiology and outcomes of multidrug-resistant tuberculosis (MDR-TB) diagnosed in Australia between 1998 and 2012. Design A retrospective review was undertaken involving all patients with laboratory-confirmed MDR-TB notified in Australia between 1998 and 2012 inclusive. Demographic, clinical and laboratory features are described. Clinical outcomes were defined according to World Health Organization definitions of treatment success (cure and treatment completion), treatment failure, death, loss to follow-up (including transfer out), or not evaluated at treatment completion. Results A total of 244 cases of MDR-TB were diagnosed in Australia during the study period, representing 1.4% of all TB cases notified. The majority were born outside Australia, including one third in Papua New Guinea. Of those with treatment outcome data available, treatment success was demonstrated in 81%. Treatment success was positively associated with use of a second-line injectable agent. Those born in Papua New Guinea were less likely to achieve treatment success. Conclusion MDR-TB is uncommon in Australia. The large number of cases born in Papua New Guinea, and the poorer outcomes in this cohort, represent challenges with cross-border management of MDR-TB in the Torres Strait. Australia has an ongoing role in the prevention and management of MDR-TB locally and in the region.

Background High incidence and serotype diversity of invasive pneumococcal disease (IPD) in Indigenous children in remote Australia led to rapid introduction of 7-valent conjugate pneumococcal vaccine (7vPCV) at 2, 4 and 6 months in 2001, followed by 23-valent polysaccharide pneumococcal vaccine (23vPPV) in the second year of life. All other Australian children were offered 3 doses of 7vPCV without a booster from 2005. This study evaluated the impact of the unique pneumococcal vaccine schedule of 7vPCV followed by the 23vPPV booster among Indigenous Australian children. Methods Changes in IPD incidence derived from population-based passive laboratory surveillance in Indigenous children

SUMMARYAlthough the incidence of invasive group A streptococcal disease in northern Australia is very high, little is known of the regional epidemiology and molecular characteristics. We conducted a case series of Northern Territory residents reported between 2011 and 2013 withStreptococcus pyogenesisolates from a normally sterile site. Of the 128 reported episodes, the incidence was disproportionately high in the Indigenous population at 69·7/100 000 compared to 8·8/100 000 in the non-Indigenous population. Novel to the Northern Territory is the extremely high incidence in haemodialysis patients of 2205·9/100 000 population; and for whom targeted infection control measures could prevent transmission. The incidences in the tropical north and semi-arid Central Australian regions were similar. Case fatality was 8% (10/128) and streptococcal toxic shock syndrome occurred in 14 (11%) episodes. Molecular typing of 82 isolates identified 28emmtypes, of which 63 (77%) were represented by fouremmclusters. Typing confirmed transmission between infant twins. While the diverse range ofemmtypes presents a challenge for effective coverage by vaccine formulations, the limited number ofemmclusters raises optimism should cluster-specific cross-protection prove efficacious. Further studies are required to determine effectiveness of chemoprophylaxis for contacts and to inform public health response.

Background Rheumatic heart disease (RHD) poses a major disease burden among disadvantaged populations globally. It results from acute rheumatic fever (ARF), a complication of Group A Streptococcal (GAS) infection. These conditions are acknowledged as diseases of poverty, however the role of specific social and environmental factors in GAS infection and progression to ARF/RHD is not well understood. The aim of this systematic review was to determine the association between social determinants of health and GAS infection, ARF and RHD, and the effect of interventions targeting these. Methodology We conducted a systematic literature review using PubMed, the Cochrane Library and Embase. Observational and experimental studies that measured: crowding, dwelling characteristics, education, employment, income, nutrition, or socioeconomic status and the relationship with GAS infection, ARF or RHD were included. Findings for each factor were assessed against the Bradford Hill criteria for evidence of causation. Study quality was assessed using a standardised tool. Principle findings 1,164 publications were identified. 90 met inclusion criteria, comprising 91 individual studies. 49 (50.5%) were poor quality in relation to the specific study question. The proportion of studies reporting significant associations between socioeconomic determinants and risk of GAS infection was 57.1%, and with ARF/RHD was 50%. Crowding was the most assessed factor (14 studies with GAS infection, 36 studies with ARF/RHD) followed by socioeconomic status (6 and 36 respectively). The majority of studies assessing crowding, dwelling characteristics, education and employment status of parents or cases, and nutrition, reported a positive association with risk of GAS infection, ARF or RHD. Crowding and socioeconomic status satisfactorily met the criteria of a causal association. There was substantial heterogeneity across all key study aspects. Conclusion The extensive literature examining the role of social determinants in GAS infection, ARF and RHD risk lacks quality. Most were observational, not interventional. Crowding as a cause of GAS infection and ARF/RHD presents a practical target for prevention actions., Author summary Rates of rheumatic heart disease (RHD) are high in disadvantaged populations globally. It results from acute rheumatic fever (ARF), a complication of Group A Streptococcal (GAS) infection. These are described as diseases of poverty, but exactly what components of poverty promote them has been unclear. The aim of this review was to find what specific social and environmental factors are associated with GAS infection, ARF and RHD, and if actions targeting these can reduce disease rates. We did a search of published literature and found 90 relevant articles. Many supported an association between GAS infection, ARF or RHD and crowding, dwelling characteristics, low education level and employment status, poor nutrition and low social class. There was enough evidence to show that crowding and socioeconomic disadvantage increase the risk of GAS infection and ARF/RHD. However, most studies were of fair to poor quality in their ability to answer the research question, and there was little interventional research. This may relate to challenges inherent in intervening to change social determinants of health, but may also suggest lesser research attention to health issues affecting disadvantaged populations. The association between crowding and disease risk strongly supports initiatives to reduce crowding. This should become a key target for ARF and RHD prevention.

To describe the clinical characteristics, risk factors, diagnostic modalities, treatments, subsequent outcomes and complications of Multidrug-resistant tuberculosis (MDR-TB) cases residing in the Northern Territory.A retrospective case series was conducted of all patients treated for MDR-TB in the Northern Territory between 1 January 2004 and 31 December 2013. This is the first study to analyse data relating to the subset of MDR-TB cases treated in the Northern Territory. Cases were identified by the Northern Territory Centre for Disease Control (NT CDC): the public health unit responsible for the management of tuberculosis in the Northern Territory. Outcome measures included patient demographics, diagnostics, HIV status, treatment methods, outcomes, and complications.Six MDR-TB cases were treated in the Northern Territory; 5 of these were notified by the NT CDC during the study period (1.5% of all Northern Territory TB notifications). The median age of all 6 patients was 31 years (range 21 to 50 years), sex distribution was equal and all were born overseas. Country of birth in a World Health Organization (WHO) high burden MDR-TB country and previous treatment were most highly correlated with a current diagnosis of MDR-TB. Access to rapid drug susceptibility testing reduced the time to effective therapy from 45 to 27 days. Five patients met criteria for the WHO outcome term 'treatment success'. The median length of treatment for the 5 patients treated in Australia was 623 days (537 to 730 days). Side effects to therapy were common and serious. The incidence of MDR-TB in the Northern Territory is similar to other Australian states. Rapid drug susceptibility testing reduces the time to effective therapy. Treatment regimens are complex, toxic and have serious resource implications for health care providers. Successful treatment outcomes are possible with coordinated TB control programs. Commun Dis Intell 2016;40(3):E334-E339.

Objective To evaluate the impact and effectiveness of the 23-valent polysaccharide pneumococcal vaccine (23vPPV) in ≥ 65-year-old Australians in the context of concurrent 7-valent pneumococcal conjugate vaccine (7vPCV) use in infants. Design, patients and setting Ecological analysis of trends in invasive pneumococcal disease (IPD) notification rates and vaccine effectiveness estimation using the screening method, using data on Australians aged ≥ 65 years (23vPPV funded) and 50-64 years (23vPPV not funded). Intervention National 23vPPV program for people aged ≥ 65 years and national 7vPCV program for infants, both commencing in 2005. Main outcome measures IPD incidence rate ratios, 2002-2004 to 2010-2011, and 23vPPV effectiveness against 23vPPV-type IPD. Results The proportion of people aged ≥ 65 years who were vaccinated within the previous 5 years in jurisdictions excluding Victoria ranged from 41% to 64% over the study period, with no clear trend over time. Incidence rate ratios in the ≥ 65-year age group were 0.11 (95% CI, 0.09-0.14) for 7vPCV serotypes, 1.64 (95% CI, 1.41-1.91) for 23vPPV-non-7vPCV serotypes and 2.07 (95% CI, 1.67-2.57) for non-23vPPV serotypes. The incidence rate ratio for total IPD was 0.65 (95% CI, 0.59-0.71) for people aged ≥ 65 years, and 0.80 (0.71-0.90) for people aged 50-64 years. The estimate of 23vPPV effectiveness was 61.1% (95% CI, 55.1%-66.9%). Conclusions The greater reduction in IPD among ≥ 65-year-olds compared with 50-64-year-olds did not reach statistical significance. However, vaccine effectiveness was significant. Greater reductions in IPD in ≥ 65-year-olds would be expected from the indirect effects of using 13-valent pneumococcal conjugate vaccine in infants (introduced for Australian infants in 2011) and an increase in 23vPPV coverage.

We report two cases of severe pneumonia due to clone ST93 methicillin-resistant Staphylococcus aureus (MRSA) presenting from a remote Australian Indigenous community within a 2-week period, and the utilization of whole genome sequences to determine whether these were part of an outbreak. S. aureus was isolated from 12 of 92 nasal swabs collected from 25 community households (including the two index households); one isolate was ST93. Three of five skin lesion S. aureus isolates obtained at the community were ST93. Whole genome sequencing of the ST93 isolates from this study and a further 20 ST93 isolates from the same region suggested that recent transmission and progression to disease had not taken place. The proximity in time and space of the two severe pneumonia cases is probably a reflection of the high burden of disease due to ST93 MRSA in this population where skin infections and household crowding are common.

BACKGROUND Australia introduced universal 7-valent pneumococcal conjugate vaccine (PCV7) from 2005, replaced by 13-valent PCV (PCV13) in 2011, uniquely among high-income countries giving doses at 2, 4, and 6 months (3 + 0 schedule). Data on impact of a timely 3 + 0 PCV schedule with high coverage are sparse, with none for PCV13. METHODS We used national surveillance of invasive pneumococcal disease (IPD) from 2002 for baseline and appropriate later comparison periods to calculate incidence rate ratios (IRRs) by serotype and age using a Poisson model. PCV coverage was assessed from the Australian Childhood Immunisation Register. RESULTS After 9 years of timely 3-dose PCV coverage of >92%, all-age IPD in Australia almost halved (IRR, 0.53; 95% confidence interval [CI], .50-.57), but differed by PCV era. Reductions in IPD due to vaccine serotypes from PCV7 (IRR, 0.20; CI, .17-.22) were about 2-fold greater than for IPD due to extra serotypes in PCV13 (13v-non7v) in a similar period (IRR, 0.58; CI, .51-.66). Post-PCV13 declines in serotype 19A IPD in persons aged

Background: A universal newborn hepatitis B (HBV) vaccination program was introduced in the Northern Territory of Australia in 1990, followed by a school-based catch-up program. We evaluated the prevalence of hepatitis B infection in birthing women up to 20 years after vaccination and compared this to women born before the programs commenced. Methods: A cohort of birthing mothers was defined from Northern Territory public hospital birth records between 2005 and 2010 and linked to laboratory confirmed notifications of chronic HBV, based principally on a record of hepatitis B surface antigen detection. Prevalence of HBV was compared between women born before or after implementation of the newborn and catch-up vaccination programs. Findings: Among 10797 birthing mothers, 138 (1.3%) linked to a chronic HBV record. HBV prevalence was substantially higher in Aboriginal women compared to non-Indigenous women (2.4% versus 0.04%; p

Background An outbreak of cutaneous sporotrichosis occurred in the Darwin region of the Northern Territory (NT) in 2014. We aimed to determine the source and risk factors associated with the outbreak and describe the clinical spectrum of cases seen. Methods Epidemiological investigation of cases of cutaneous sporotrichosis identified through the Royal Darwin Hospital was undertaken to investigate risk factors and potential sources of infection. Data were collected through chart review and individual patient interviews. Environmental investigation followed identification of a common risk factor. Results Nine confirmed cases of cutaneous sporotrichosis caused by Sporothrix schenckii were identified with onset of symptoms between April and July 2014. Patients were aged 29 to 70 years and seven were male (78 %). Two strains of S. schenckii were identified, neither of which have been previously documented. One common risk factor was identified: all patients were occupational or recreational gardeners, with each reporting exposure to mulching hay, originating from a single NT farm. Local environmental health officers visited the farm and the owners confirmed that the implicated hay had been stored over the monsoon season and had been affected by rain. Storage of hay over the wet season was a new practice. Conclusions This constitutes the third reported outbreak of S. schenckii sporotrichosis attributable to contaminated hay in Australia and the first outbreak of sporotrichosis in the NT. This outbreak prompted public health interventions, including distribution of information to general practitioners, farmers and suppliers in the Top End. Media reporting led to the identification and treatment of an additional case. Local practitioners should remain alert to the possibility of further occurrences of sporotrichosis.

Objectives: To assess the prevalence of latent tuberculosis infection (LTBI) in recently arrived refugees in the Northern Territory and to obtain comprehensive data for rates of treatment acceptance and completion for this condition. Design, setting and participants: Prospective data collection and follow-up of all 471 newly arrived refugees seen at the Centre for Disease Control, NT refugee health clinic from February 2006 to January 2009. Main outcome measures: Rates of LTBI determined by tuberculin skin testing; subsequent assessment and treatment compared with local protocols. Results: 458 of 465 eligible refugees were adequately assessed for LTBI, of whom 146 (31.9%) were diagnosed with LTBI. Older age, male sex and World Health Organization Eastern Mediterranean region of birth were associated with increased prevalences of LTBI. Of the refugees diagnosed with LTBI, 10 failed to attend for follow-up and 15 were not offered treatment. Isoniazid therapy was accepted by 93 of 121 refugees (76.9%), and 41 of these (44.1%) completed treatment. The most common reasons for discontinuation of therapy were medication-related side effects (most often gastrointestinal) and loss to follow-up. Increasing age was associated with failure to complete treatment. Conclusion: Outcomes of assessment and treatment for LTBI in newly arrived refugees in the NT are comparable to those for other target groups screened in developed countries. Loss to follow-up caused significant attrition in numbers, but complete data were obtained for a large proportion of eligible refugees. Most refugees who are offered MJA 2011; 194: 579–582 treatment for LTBI accept, but less than half complete treatment.

Over the last decade, there has been no discernible reduction in Invasive Pneumococcal Disease (IPD) amongst Indigenous adults in the Northern Territory (NT) of Australia, despite increasing vaccination coverage. We examined the utility of two common methods, the screening method and the indirect method, to determine the 23-valent pneumococcal polysaccharide vaccine effectiveness (VE) in prevention of IPD amongst Indigenous adults in this setting. VE was calculated for the period 2001-2005 across two distinct geographical areas where the disease burden was known to differ. VE against vaccine-type IPD was 3.4% (95% CI -43, 35) for the NT. However, population vaccination coverage varied widely according to geographical region and where this was within the range appropriate for the use of the screening method, VE was within the expected range (67.2%, 95% CI 47, 80). VE according to the indirect cohort appeared unreliable in this setting due to the analysis being based on a very limited number of non-vaccine-type IPD cases. Surveillance based estimates of VE such as these need to be considered with caution, but the results suggest failure to vaccinate is the most likely reason vaccine-type IPD has not reduced in this setting.

About 13 000 refugees are currently accepted for migration into Australia each year, many of whom have spent protracted periods living in extremely disadvantaged circumstances. As a result, medical practitioners are increasingly managing recently arrived refugees with acute and chronic infectious diseases. The Australasian Society for Infectious Diseases has formulated guidelines for the diagnosis, management and prevention of infection in newly arrived refugees. This article is an abridged version of the guidelines, which are available in full at http://www.asid.net.au. All refugees should be offered a comprehensive health assessment, ideally within 1 month of arrival in Australia, that includes screening for and treatment of tuberculosis, malaria, blood-borne viral infections, schistosomiasis, helminth infection, sexually transmitted infections, and other infections (eg, Helicobacter pylori) as indicated by clinical assessment; and assessment of immunisation status, and catch-up immunisations where appropriate. The assessment can be undertaken by a general practitioner or within a multidisciplinary refugee health clinic, with use of an appropriate interpreter when required. The initial assessment should take place over at least two visits: the first for initial assessment and investigation and the second for review of results and treatment or referral.

Childhood immunisation coverage reported at 12 to

Objective: To document demographic details, prevalence of tuberculosis (TB), and completion of TB treatment in illegal foreign fishermen detained in Australia. Design and participants: Clinical audit of 1471 illegal foreign fishermen who underwent health assessments in Darwin between 28 September 2005 and 31 December 2006. Main outcome measures: Demographic details, diagnoses of smear-positive and culture-positive TB, drug sensitivity results and treatment completion. Results: 1471 illegal fishermen underwent health assessments, including chest x-ray screening. All were male and 93.8% were from Indonesia. Of the 31 fishermen (2.1%) admitted to hospital with chest x-rays suggestive of TB, 20 were diagnosed with TB (15 culture-proven; 5 according to clinical and radiological criteria) and 18 commenced treatment. There were 8 smear-positive cases and one multidrug-resistant TB case. The prevalence of culture-positive TB was very high at 1020 per 100 000 patients. All fishermen were deported before treatment completion, and all were lost to follow-up. Conclusions: The health assessment process successfully detected cases of TB in illegal foreign fishermen, enabling treatment to commence and the local public’s health to be protected. Treatment completion in illegal foreign fishermen may be as low as zero; deporting fishermen before curative treatment is completed undermines TB control efforts and may lead to an emergence of drug resistance and an increased burden of

Summary Objectives To determine the prevalence of Salmonella in the environment of case and control houses, and compare serovars isolated from cases and their houses. Methods From 2005 to 2008, we tested samples from houses of 0–4 year old cases and community controls in Darwin and Palmerston for Salmonella . Case isolates were compared with environmental isolates. S . Ball and S . Urbana isolates were compared using Multiple Amplification of Phage Locus Typing (MAPLT) and Multiple-Locus Variable number of tandem repeat Analysis (MLVA). Results Salmonella were found in 47/65 (72%) case houses and 18/29 (62%) control houses; these proportions were not significantly different. In 21/47 (45%) houses, case and environmental isolates (from animal faeces, soil and vacuums) were indistinguishable. Multiple serovars were isolated from 20 (31%) case and 6 (21%) control houses. All but one environmental isolate are known human pathogens in the Northern Territory (NT). Each of the four pairs of S. Ball and S. Urbana were indistinguishable. Conclusions Animal faeces were the most likely source of salmonellosis in cases. The similar prevalence of house isolates suggests that Salmonella is ubiquitous in this environment. The distinction of S. Ball and S. Urbana subtypes enabled linkage of human illness to environmental exposure. Environmental contamination with Salmonella is an important source of sporadic infection in children in the tropics.

Summary Objectives The aims of this study were to describe the epidemiology of melioidosis in tropical northern Australia and to assess the importance of defined risk factors. Methods The data were taken from a 14-year prospective study of 364 cases of melioidosis in the ‘Top End’ of the Northern Territory. A whole-population logistic regression model was used to estimate the crude and adjusted relative risk (RR) for the defined risk factors. Results The mean age of the study population was 46.8 years, 264 (72.5%) were male, 178 (49%) were aboriginal Australians and 59 (16.2%) died from melioidosis. Average annual incidence was 19.6 cases per 100 000 population, with an estimated rate of 260 cases per 100 000 diabetics per year. Using a whole-population logistic regression model, the estimated crude and adjusted RR [95% confidence intervals (CI)] for melioidosis were 6.3 (5.1–7.8) and 4.0 (3.2–5.1) for those aged ≥ 45 years, 2.3 (1.8–2.9) and 2.4 (1.9–3.0) for males, 2.9 (2.3–3.5) and 3.0 (2.3–4.0) for aboriginal Australians, 21.2 (17.1–26.3) and 13.1 (9.4–18.1) for diabetics, 2.7 (2.2–3.4) and 2.1 (1.6–2.6) for those with excess alcohol consumption, 6.8 (5.4–8.6) and 4.3 (3.4–5.5) for chronic lung disease and 6.7 (4.7–9.6) and 3.2 (2.2–4.8) for chronic renal disease, respectively. Conclusions Diabetes, excess alcohol intake, chronic renal disease and chronic lung disease are each independent risk factors for melioidosis. In tropical northern Australia, male sex, aboriginal ethnicity and age of ≥45 years are also independent predictors for melioidosis. Impaired polymorph function may be critical in the predisposition to melioidosis.

Chlamydia trachomatis conjunctival samples collected over a 6-month period from individuals with clinical signs of trachoma and located in remote communities in the Australian Northern Territory were differentially characterized according to serovar and variants. The rationale was to gain an understanding of the epidemiology of an apparent increased prevalence of acute trachoma in areas thought to be less conducive to this disease. Characterization was performed through sequencing of a region of the omp1 gene spanning the four variable domains and encoding the major outer membrane protein. Nucleotide and deduced amino acid sequences were genotyped by using a BLAST similarity search and were examined by phylogenetic analyses to illustrate evolutionary relationships between the clinical and GenBank reference strains. The predominant genotype identified corresponded to that of serovar C (87.1%), followed by the genotype corresponding to serovar Ba (12.9%). All nucleotide and amino acid sequences exhibited minor levels of variation with respect to GenBank reference sequences. The omp1 nucleotide sequences of the clinical samples best aligned with those of the conjunctival C . trachomatis reference strains C/TW-3/OT and Ba/Apache-2. All clinical samples (of serovar C) exhibited four or five nucleotide changes compared with C/TW-3/OT, while all serovar Ba samples had one or two nucleotide differences from Ba/Apache-2. Phylogenetic analyses revealed close relationships between these Northern Territory chlamydial samples and the respective reference strains, although the high proportion of sequence variants suggests an evolutionarily distinct C . trachomatis population causing eye infections in Australia. Given that such genotypic information has gone unreported, these findings provide knowledge and a foundation for trachoma-associated C . trachomatis variants circulating in the Northern Territory.

We performed a retrospective/prospective review of all cases of disease due to nontuberculous mycobacteria (NTM) reported in the Northern Territory, Australia, during the period 1989-1997. Fifty-eight cases were reported, with an average yearly incidence of 3.9 cases per 100,000 persons. The number increased significantly for the second half of the study period (39 vs. 19 cases; P.02). The yearly incidence of pulmonary Mycobacterium avium/Mycobacterium intracellulare complex (MAC) disease not associated with human immunodeficiency virus (HIV) infection was 2.1 cases per 100,000 population. MAC was the most common isolate (78%) and pulmonary disease the most frequent clinical presentation (62%). Disease due to NTM or MAC was not found more commonly in rural areas. Significant risks for non-HIV-associated pulmonary MAC disease included male sex (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.0-4.5) and age50 years (OR, 26.5; 95% CI, 10.9-67.3), but aboriginal people appeared underrepresented (OR, 0.77; 95% CI, 0.30-1.87). Mycobacterium tuberculosis was almost 5 times more likely than NTM to be the cause of non-HIV-associated mycobacterial pulmonary disease (153 vs. 32 cases; OR, 4.79; 95% CI, 3.22-7.14). Mycobacterial lymphadenitis in aboriginal children was more likely to be tuberculous than nontuberculous (OR, 6.5; 95% CI, 1.4-41.7), but not in nonaboriginal children (OR, 1.0). With treatment, 66% of the cases of non-HIV-associated pulmonary MAC disease had favorable outcomes, and 7% of patients had progressive fatal disease. Outcomes of therapy for lymphadenitis and skin/soft-tissue disease were excellent, but those of HIV-associated disseminated MAC disease were poor.