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.

Indigenous populations globally are disproportionately affected by chronic hepatitis B virus (HBV) infection however contemporary sero-prevalence data are often absent. In the Indigenous population of the Northern Territory (NT) of Australia the unique C4 sub-genotype of HBV universally circulates. There are no studies of the sero-prevalence, nor the impact of the vaccination program (which has a serotype mismatch compared to C4), at a population-wide level. We examined all available HBV serology results obtained from the three main laboratories serving NT residents between 1991 and 2011. Data were linked with a NT government database to determine Indigenous status and the most recent test results for each individual were extracted as a cross-sectional database including 88,112 unique individuals. The primary aim was to obtain a contemporary estimate of HBsAg positivity for the NT by Indigenous status. Based on all tests from 2007-2011 (35,633 individuals), hepatitis B surface antigen (HBsAg) positivity was 3·40% (95%CI 3·19-3·61), being higher in Indigenous (6·08%[5·65%-6·53%]) than non-Indigenous (1·56%[1·38%-1·76%]) Australians, p<0·0001. Birth cohort analysis showed HBsAg positivity fell over time for Indigenous people, with this decrease commencing prior to universal infant vaccination (which commenced in 1990), with an ongoing but slower rate of decline since 1990, (0·23% decrease per year versus 0·17%). HBsAg positivity is high in the NT, particularly in the Indigenous population. HBsAg positivity has fallen over time but a substantial part of this decrease is due to factors other than the universal vaccination program.

In tropical northern Australia, approximately 20% of Staphylococcus aureus bacteremia is caused by methicillin-resistant Staphylococcus aureus (MRSA). We prospectively evaluated the impact on clinician antibiotic prescribing of the results obtained from performing the GeneXpert MRSA/SA test on 151 positive blood cultures with clustered gram-positive cocci. The GeneXpert result led to earlier appropriate prescription of vancomycin for 54% of patients with MRSA; 25% of patients avoided vancomycin, and 16% of patients had all antibiotics ceased.

BACKGROUND AND AIM: The hepatitis B surface antigen was first described in the blood of an Indigenous Australian man, yet little is known about its molecular epidemiology in this population, in which it is endemic. The study aimed to determine the clinical and molecular epidemiology of hepatitis B virus (HBV) in Indigenous people from northern Australia. METHODS: Following ethics approval and informed consent, blood specimens and clinical details from Indigenous adults known to be infected with HBV and who were born and raised in Indigenous communities in northern Australia were obtained. HBV genotypes were determined in isolates with sufficient HBV DNA by polymerase chain reaction by sequencing of the polymerase/surface gene. RESULTS: Between June 2010 and June 2012, 65 patients were recruited from six different regions of northern Australia. Thirty-two patients (49%) were hepatitis B e-antigen-positive, and 48% were hepatitis B e-antibody-positive. No patients were found to be coinfected with hepatitis C virus or human immunodeficiency virus. Of the 49 samples with sufficient viral load for genotyping, 100% were infected with genotype C4, previously only reported from two Indigenous Australians. All isolates had wild-type polymerase gene sequences despite 14 currently or previously receiving antiviral treatment. The canonical sG145R vaccine-escape variant was detected in the surface antigen of virus from two patients. CONCLUSIONS: The exclusive HBV genotype in this ancient population is genotype C4. Whole genome sequencing and clinical follow-up of this cohort are in progress, with the aim of exploring the clinical significance of these findings.

To establish the relationship between hepatitis B virus (HBV) and human T-cell lymphotropic virus type 1 (HTLV-1) serological markers in the Northern Territory, Australia. A retrospective serological study of patients presenting to public healthcare facilities in the Northern Territory between 2008 and 2015 was performed in order to determine the presence and relationships of serological markers of HBV and HTLV-1. Seven hundred and forty individual patients were found to be serologically positive for HTLV-1 in the Northern Territory over the 8-year period. Hepatitis B results were available for 521 of these patients. Hepatitis B surface antigen (HBsAg) positivity was demonstrated in 15.9% (83/521) of this cohort, which was significantly different to the HTLV-1-negative group (3.7%, 125/3354) (p<0.001). Excluding individuals with isolated hepatitis B surface antibody (anti-HBs), those in the HTLV-1-positive group had a higher HBV exposure history (67.5%, 352/521) when compared to HTLV-1-negative individuals (37.8%, 1259/3354) (p<0.001). HTLV-1-positive individuals had a lower prevalence of HBV combined anti-HBs and hepatitis B core antibody (anti-HBc) positive markers compared to those who were HTLV-1-negative (56.3% (198/352) versus 73.8% (937/1269), respectively; p<0.001). A significantly higher prevalence rate of HBV was found in HTLV-1-positive individuals from the Northern Territory. When considering the higher exposure to HBV in HTLV-1-positive individuals, the clearance of HBV appears lower than in those individuals testing HTLV-1-negative. A lower prevalence of clearance in HTVL-1-positive individuals than in HTLV-1-negative individuals, as signified by formation of HBVcAb and HBVsAb in HTVL-1 positive individual's may equate to higher prevalence of ongoing coinfection.

  To describe the incidence and prevalence of blood-borne viruses (BBV) including: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and human T-cell leukaemia virus type-1 (HTLV) in the haemodialysis-dependent population of the Top End of the Northern Territory (TENT).   We retrospectively reviewed the serology of BBV in a longitudinal fashion in the haemodialysis-dependent population treated in the TENT of Australia from 2000 to 2009 inclusive. HBV, HCV, HIV and HTLV serology on commencement of dialysis and at exit or January 2010, whichever was earlier, as well as demographic details were collected. Patients with a change in serological status had all serology reviewed.   Four-hundred and forty patients were included in the analysis. Of these, 84.3% were Indigenous and 55.4% female, with a median age of 50 (IQR 43-59) years at the commencement of haemodialysis. Evidence of past HBV infection was documented in 42.7% and 8.9% were hepatitis B surface antigen-positive. Positive serology for HTLV was documented in 2.2%, 1.6% were hepatitis C antibody-positive and no individual was HIV-positive. Three patients had a definite change in their HBV serology over time; this equates to an absolute seroconversion risk of 0.1 per 100 person years or 0.0006 per dialysis episode.   In this cohort, there was a high rate of past and current hepatitis B infection but low rates of seroconversion while on haemodialysis.

OBJECTIVES: To determine the prevalence and trends of human hookworm infection (HWI) in the Northern Territory over the past 10 years, and to assess the influence of the community children's deworming program (CCDP). DESIGN, PATIENTS AND SETTING: A retrospective observational analysis of consecutive microbiologically confirmed cases of HWI in patients diagnosed at NT government health care facilities and the main private laboratory servicing the NT between January 2002 and July 2012. MAIN OUTCOME MEASURES: Annual prevalence of HWI (2002-2011); age, sex, Indigenous status, residence, haemoglobin level and eosinophil count of patients with HWI; and proportion of patients within the CCDP target population (children aged 6 months to 16 years, who should receive 6-monthly albendazole). RESULTS: From 64 691 faecal samples examined during the study period, hookworm was detected in 112 patients. There was a downward trend in the annual prevalence of HWI, falling from 14.0 cases per 100 000 population (95% CI, 8.8-19.2) in 2002 to 2.2 per 100 000 population (95% CI, 0.3-4.1) in 2011. Only 16 patients (14.3%) fell within the CCDP target population. Seventy-one patients (63.4%) were living in remote communities, and 94 (84.7%) were recorded as Indigenous Australians. CONCLUSIONS: The prevalence of HWI in the NT reduced over the 10-2013 period. HWI predominantly occurs in individuals outside the CCDP target population. Our data support continuation of the CCDP in conjunction with improvements in housing, health hardware and health promotion. Continued use of albendazole in individuals beyond the CCDP may facilitate the eventual eradication of HWI from the NT.