A retrospective study of 191 cases of septic arthritis was undertaken at Royal Darwin Hospital in the tropical north of Australia. Incidence was 9.2 per 100,000 overall and 29.1 per 100,000 in Aboriginal Australians (RR 6.6; 95% CI 5.0-8.9). Males were affected more than females (RR 1.6; 95% CI 1.2-2.1). There was no previous joint disease or medical illness in 54%. The commonest joints involved were the knee (54%) and hip (13%). Significant age associations were infected hips in those under 15 years and infected knees in those over 45 years. Seventy two percent of infections were haematogenous. Causative organisms included Staphylococcus aureus (37%), Streptococcus pyogenes (16%) and Neisseria gonorrhoeae (12%). Unusual infections included three melioidosis cases. Polyarthritis occurred in 17%, with N. gonorrhoeae (11/23) more likely to present as polyarthritis than other organisms (22/168) (OR 6.0; 95% CI 2.1-16.7). Univariate and multivariate analysis showed the hip to be at greater risk for S. aureus than other joints. Open arthrotomy was a more successful treatment procedure than arthroscopic washout or needle aspiration.

From November 1990 to June 1991 33 acute cases of melioidosis occurred in the Northern Territory, Australia; 25 cases were reported in the capital city, Darwin. We carried out an epidemiological investigation to exclude a common source outbreak, describe the risk factors for disease, and develop and institute appropriate control measures. We compared population based attack rates among various risk groups using logistic regression, and the demographic, medical and behavioral risk factors for melioidosis by a matched case-control study. Environmental Health Officers collected soil, surface water and cooling tower water specimens for Pseudomonas pseudomallei culture. The crude attack rate of melioidosis during the outbreak was 52 per 100,000. Age, gender, race, diabetes and alcohol abuse were independent risk factors for disease. The relative risk of disease in diabetic patients was 12.9 (95% CI 5.1-32.7; p < 0.001) and 6.7 in alcoholic patients (95% CI 2.9-15.2; p < 0.001). We found no significant difference between cases and controls in matched pair analysis for any of several exposure factors studied. We isolated Pseudomonas pseudomallei from 4% of soil samples and 9% of surface water samples. Our study confirms the importance of host factors in the development of melioidosis, and attempts to quantify the risk of disease during the Darwin epidemic. Pseudomonas pseudomallei is widespread in the soil of urban Darwin.

The apparent incidence of acute hepatitis B infection in the Top End of the Northern Territory was estimated from notification data and hospital data to be 12 per 100,000 per year, with a marked difference between Aborigines (42 per 100,000) and non-Aborigines (4 per 100,000), and an odds ratio of 9.7 (95 per cent confidence intervals 3 to 33). Sixty percent of Aboriginal cases of acute hepatitis B occurred in children under 10 years of age, whereas non-Aboriginal cases occurred in adults aged 20 to 29, most with behavioural risk factors. These findings confirm the importance of immunising Aboriginal children to reduce the future incidence of hepatitis B infection and hepatoma.

Adrenal crises are life-threatening complications of adrenal insufficiency. These events have an estimated incidence of between 5 and 10  adrenal crises/100 patient years and are responsible for some of the increased morbidity and excess mortality experienced by patients with adrenal insufficiency. Treatment involves urgent administration of IV/IM hydrocortisone and IV fluids. Patient education regarding preventive measures, such as increasing the dose of replacement therapy ("stress dosing") when sick, using parenteral hydrocortisone as necessary and accessing medical assistance promptly, is still considered the best approach to averting the onset of an adrenal crisis at times of physiological stress, most commonly an infection. However, recent evidence has demonstrated that patient education does not prevent many adrenal crisis events and the reasons for this are not fully understood. Furthermore, there is no widely accepted definition of an adrenal crisis. Without a validated adrenal crisis definition it is difficult to interpret variations in the incidence of adrenal crises and determine the effectiveness of preventive measures. This article aims to review the clinical aspects of adrenal crisis events, to explore the epidemiology, and to offer a definition of an adrenal crisis and to offer a perspective on future directions for research into adrenal crisis prevention.

Survival after a stroke is lower for Indigenous than other stroke patients in Australia. It is not known whether recurrence is more common for Indigenous patients, or whether their higher prevalence of comorbidity affects their lower survival. This study aimed to investigate the stroke recurrence and role of comorbidities in adverse stroke outcomes (recurrence and death) for Indigenous compared with other Australians. A retrospective cohort study of first hospitalization for stroke (n = 2105) recorded in Northern Territory hospital inpatient data between 1996 and 2011 was conducted. For the multivariable analyses of adverse outcomes, logistic regression was used for case fatality and competing risk analysis for recurrent stroke and long-term death. Comorbidities (identified from inpatient diagnosis data) were analyzed using the Charlson Comorbidity Index (modified for stroke outcomes). Prevalence of comorbidities, case fatality, incidence of re-hospitalization for recurrent stroke, and long-term death rate were higher for Indigenous than non-Indigenous stroke patients. Adjustment for comorbidity in multivariable analyses considerably reduced Indigenous patients' excess risk for case fatality (odds ratio: 1·25, 0·88-1·78) and long-term death (standard hazard ratio: 1·27, 1·01-1·61) (but not recurrence), implying that their excess risk of death was in part due to higher comorbidity prevalence. Indigenous stroke patients have higher prevalence of comorbidities than non-Indigenous stroke patients, which explained part of the disparity in both case fatality and long-term survival but did not explain the disparity in stroke recurrence at all.

This report describes the epidemiology of mosquito-borne diseases of public health importance in Australia during the 2013-14 season (1 July 2013 to 30 June 2014) and includes data from human notifications, sentinel chicken, vector and virus surveillance programs. The National Notifiable Diseases Surveillance System received notifications for 8,898 cases of disease transmitted by mosquitoes during the 2013-14 season. The Australasian alphaviruses Barmah Forest virus and Ross River virus accounted for 6,372 (72%) total notifications. However, over-diagnosis and possible false positive diagnostic test results for these 2 infections mean that the true burden of infection is likely overestimated, and as a consequence, the case definitions have been amended. There were 94 notifications of imported chikungunya virus infection and 13 cases of imported Zika virus infection. There were 212 notifications of dengue virus infection acquired in Australia and 1,795 cases acquired overseas, with an additional 14 cases for which the place of acquisition was unknown. Imported cases of dengue were most frequently acquired in Indonesia (51%). No cases of locally-acquired malaria were notified during the 2013-14 season, though there were 373 notifications of overseas-acquired malaria. In 2013-14, arbovirus and mosquito surveillance programs were conducted in most jurisdictions. Surveillance for exotic mosquitoes at international ports of entry continues to be a vital part of preventing the spread of vectors of mosquito-borne diseases such as dengue to new areas of Australia, with 13 detections of exotic mosquitoes at the ports of entry in 2013-14.

To assess the relationships of diabetes and albuminuria with all-cause mortality and cardiovascular disease outcomes in a population without prior cardiovascular disease using data from the Darwin Region Urban Indigenous Diabetes (DRUID) study. We conducted a prospective cohort study of 706 participants (aged 15-81 years, 68% women) without prior cardiovascular disease who underwent a 75-g oral glucose tolerance test. Deaths and fatal or non-fatal cardiovascular disease were determined over 7 years, and hazard ratios with 95% CIs and population attributable risks were estimated for baseline glycaemia and albuminuria. Compared with normoglycaemia and after adjustment for age, sex, hypertension, dyslipidaemia and smoking, known diabetes was associated with an adjusted hazard ratio of 4.8 (95% CI 1.5-14.7) for all-cause mortality and 5.6 (95% CI 2.1-15.2) for cardiovascular disease. Compared with normoalbuminuria, the respective adjusted risks for macroalbuminuria were 10.9 (95% CI 3.7-32.1) and 3.9 (95% CI 1.4-10.8). The Adjusted all-cause mortality and cardiovascular disease estimated population attributable risks for diabetes were 27% and 32%, and for albuminuria they were 32% and 21%, respectively. In our study population, the burden of mortality and cardiovascular disease was largely driven by diabetes and albuminuria. This finding on the influence of diabetes and albuminuria is consistent with reports in other high-risk Indigenous populations and should be better reflected in risk scores and intervention programmes.

  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.

To describe the incidence and mortality of invasive infections in Indigenous children admitted to paediatric and general intensive care units (ICUs) in Australia. Retrospective multi-centre cohort study of Australian and New Zealand Paediatric Intensive Care Registry data. All children under 16 years of age admitted to an ICU in Australia, 1 January 2002 - 31 December 2013. Indigenous children were defined as those identified as Aboriginal and/or Torres Strait Islander in a mandatory admissions dataset. Population-based ICU mortality and admission rates. Invasive infections accounted for 23.0% of non-elective ICU admissions of Indigenous children (726 of 3150), resulting in an admission rate of 47.6 per 100 000 children per year. Staphylococcus aureus was the leading pathogen identified in children with sepsis/septic shock (incidence, 4.42 per 100 000 Indigenous children per year; 0.57 per 100 000 non-Indigenous children per year; incidence rate ratio 7.7; 95% CI, 5.8-10.1; P < 0.001). While crude and risk-adjusted ICU mortality related to invasive infections was not significantly different for Indigenous and non-Indigenous children (odds ratio, 0.75; 95% CI, 0.53-1.07; P = 0.12), the estimated population-based age-standardised mortality rate for invasive infections was significantly higher for Indigenous children (2.67 per 100 000 per year v 1.04 per 100 000 per year; crude incidence rate ratio, 2.65; 95% CI, 1.88-3.64; P < 0.001). The ICU admission rate for severe infections was several times higher for Indigenous than for non-Indigenous children, particularly for S. aureus infections. While ICU case fatality rates were similar, the population-based mortality was more than twice as high for Indigenous children. Our study highlights an important area of inequality in health care for Indigenous children in a high income country that needs urgent attention.

Accurate diagnosis of acute rheumatic fever (ARF) remains problematic in high-incidence settings and especially in the Aboriginal population of Australia's Northern Territory. Previous investigators have demonstrated that strict application of the 1992 Updated Jones Criteria results in under-diagnosis. This study's objectives were to review use of the Jones Criteria (1992 Update) in diagnosing ARF in Australian Aboriginal patients presenting with suspected rheumatic fever, and formulate a locally relevant algorithm to improve diagnosis. Patients presenting to Royal Darwin Hospital with suspected ARF were prospectively assessed during a 15-month period. Demographic information, clinical history, examination, laboratory and echocardiographic findings were documented in order to determine whether the Jones Criteria were fulfilled, and to identify alternative diagnoses. The hospital discharge diagnosis was recorded and patients were followed up 18-33 months later. Out of 35 patients with suspected ARF, all were Aboriginal Australians, 17 (49%) had a discharge diagnosis of definite ARF, 7 (20%) had definite non-rheumatic fever diagnoses (disseminated gonococcal infection, systemic lupus erythematosis, buttock abscess and other febrile illnesses in children with cardiac murmur due to previously undiagnosed RHD). The remaining 11 (31%) posed diagnostic difficulties because of mild symptoms that failed to fulfil Jones Criteria (attracting diagnoses such as 'unexplained arthralgia') or atypical features such as older age. Two patients whose illness initially failed to fulfil the Jones Criteria, who were neither diagnosed with ARF nor commenced on secondary benzathine penicillin prophylaxis, were found on follow-up to have definite and probable ARF, respectively. At least 29% (8/28) of patients without prior recognised ARF/RHD had echocardiographic evidence of established RHD, indicating that previous episodes were missed. Individual mild episodes of ARF may be overlooked, with patients missing out on the timely institution of secondary prophylaxis. The Jones Criteria should be supplemented by active exclusion of differential diagnoses and vigilant follow-up including echocardiography. 'Probable' and 'possible ARF' should be recognised as diagnostic categories applying to patients not fulfilling the Jones Criteria but who nevertheless should be offered prophylactic penicillin at least until further follow-up. A set of diagnostic guidelines is proposed.

Invasive group A streptococcus (iGAS) disease is an important cause of mortality globally. The incidence of iGAS in Australia's tropical Northern Territory (NT) has been previously reported as 32.2/100 000 in Indigenous people for the period 1991-1996. We aimed to measure the incidence and severity of iGAS disease in the NT since this time. We collected demographic data for all GAS blood culture isolates over a 12-year period (1998-2009) from the three hospital laboratories serving the tropical NT. We then collected detailed clinical information from hospital records and databases for the subset of these patients who were admitted to Royal Darwin Hospital during 2005-2009. There were 295 confirmed cases of GAS bacteraemia over the study period, with a mean (SD) age of 42.1 (22.0) years, and 163 (55.0%) were male. The annual age-adjusted incidence was 15.2 (95% CI 13.4-16.9)/100 000 overall and 59.4 (95% CI 51.2-67.6) in Indigenous Australians. For 2005-2009, there were 123 cases with the most common focus of infection being skin/soft tissue [44 (35.6%)]; 29 patients (23.6%) required intensive care unit admission and 20 (16.3%) had streptococcal toxic shock syndrome. Antecedent sore throat or use of non-steroidal anti-inflammatory drugs was rare, but current or recent scabies, pyoderma and trauma were common. The incidence and severity of iGAS are high and increasing in tropical northern Australia, and urgent attention is needed to improve surveillance and the social determinants of health in this population. This study adds to emerging data suggesting increasing importance of iGAS in low- and middle-income settings globally.

Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia.These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne™.A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 population. The median patient age was 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles; only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/echinocandin co-resistance.We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.

Reports of increasing incidence and severity of invasive group A streptococcal (GAS) infections come mainly from affluent populations where exposure to GAS is relatively infrequent. We conducted a 6-year retrospective review of GAS bacteraemia in the Northern Territory of Australia, comparing the Aboriginal population (24% of the study population), who have high rates of other streptococcal infections and sequelae, to the non-Aboriginal population. Of 72 episodes, 44 (61%) were in Aboriginal patients. All 12 cases in children were Aboriginal. Risk factors were implicated in 82% of episodes (91% in adults) and there was no significant difference in the proportion of Aboriginal compared to non-Aboriginal patients with at least one risk factor. Genetic typing of isolates revealed no dominant strains and no evidence of a clone which has been a common cause of these infections elsewhere.

Some strains of non-multidrug-resistant, methicillin-resistant Staphylococcus aureus (nmMRSA) in Australia are likely to have emerged from strains of methicillin-susceptible S. aureus (MSSA) in remote Aboriginal communities. To describe the clinical epidemiology of infection due to community-associated MRSA strains in an Australian tropical hospital setting with a significant Aboriginal population and to compare infections caused by community-associated strains of MRSA, health-care-associated strains of MRSA, and MSSA strains with respect to demographic risk factors and clinical outcomes. Methods. We queried the microbiology database for the Top End of the Northern Territory, Australia, to determine population incidences for S. aureus infection and conducted a prospective matched case-control study to compare infection due to nmMRSA, MSSA, or multidrug-resistant MRSA at the Royal Darwin Hospital. The annual incidence of S. aureus bacteremia was 65 cases per 100,000 population, but in the Aboriginal population the incidence was 172 cases per 100,000 population (odds ratio [OR] compared with non-Aboriginal population, 5.8 [95% confidence interval {CI}, 3.8-8.9). Female sex (adjusted OR [aOR], 1.5 [95% CI, 1.1-2.0) and remote residence (aOR, 1.8 [95% CI, 1.2-2.5]) were associated with the isolation of nmMRSA rather than MSSA, but disease spectrum and outcomes were similar. Among those from whom nmMRSA was isolated, Aboriginal patients were younger (aOR for each additional year, 0.94 [95% CI, 0.92-0.96]), more likely to be female (aOR, 3.8 [95% CI, 1.7-8.5]), and more likely to reside in a remote community (aOR, 29 [95% CI, 8.9-94]) than non-Aboriginal patients. The presence of Panton-Valentine leukocidin in nmMRSA was associated with double the odds of sepsis (aOR, 2.2 [95% CI, 1.1-4.6]). The association of nmMRSA infection with female sex and remote residence supports the hypothesis that nmMRSA arose from MSSA strains in remote Aboriginal communities where staphylococcal disease is highly prevalent. The similar clinical spectrum and outcomes for nmMRSA infection and MSSA infection suggest that virulence is not correlated with resistance phenotype.

To determine the incidence of congenital heart defects (CHD) in Aboriginal and non-Aboriginal infants in Central Australia and to compare this with the incidence elsewhere in Australia. Data on cases were obtained from patient records of the Alice Springs Hospital, Central Australia, the sole referral centre for paediatric and initial cardiac diagnostic services for the region. Patients with CHD proven by echocardiography reported between 1 January 1993 and 30 June 2000. Incidence of CHD using all live births in Central Australia as the denominator. 108 patients with CHD were detected among 6156 live births (incidence, 17.5 per 1000; 95% CI, 14.9-21.7 per 1000); 57 of 2991 were Aboriginal (19.0 per 1000; 95% CI, 14.4-24.6 per 1000) and 51 of 3165 were non-Aboriginal (16.1 per 1000; 95% CI, 12.0-21.1 per 1000). The difference between the two groups was not statistically significant (relative risk, 1.18; 95% CI, 0.81-1.72). CHD incidence in Central Australia was significantly higher than that reported for other parts of Australia (4.3 per 1000 live births in New South Wales and the Australian Capital Territory, 1981-1984; 7.65 and 12 per 1000 total births in Western Australia, 1980-1989, and South Australia, 1993-2000, respectively). The high rates of CHD in Central Australia may partly reflect the high utilisation of echocardiography for assessing minor lesions. However, the incidence of both major and minor types of CHD was significantly higher than previously reported from other regions of Australia. The role of socioenvironmental factors in this high incidence should be explored.

Encephalitis is a complex neurological syndrome caused by inflammation of the brain parenchyma. The management of encephalitis is challenging because: the differential diagnosis of encephalopathy is broad; there is often rapid disease progression; it often requires intensive supportive management; and there are many aetiologic agents for which there is no definitive treatment. Patients with possible meningoencephalitis are often encountered in the emergency care environment where clinicians must consider differential diagnoses, perform appropriate investigations and initiate empiric antimicrobials. For patients who require admission to hospital and in whom encephalitis is likely, a staged approach to investigation and management is preferred with the potential involvement of multiple medical specialties. Key considerations in the investigation and management of patients with encephalitis addressed in this guideline include: Which first-line investigations should be performed?; Which aetiologies should be considered possible based on clinical features, risk factors and radiological features?; What tests should be arranged in order to diagnose the common causes of encephalitis?; When to consider empiric antimicrobials and immune modulatory therapies?; and What is the role of brain biopsy?

The Royal Darwin Hospital (RDH) services a relatively large and geographically remote Aboriginal population who account for 45% of intensive care unit admissions. Critical illness in the Aboriginal population is different from the non-Aboriginal population of the "Top End" of the Northern Territory. The critically ill Aboriginal patient is younger, has more chronic health problems and a higher severity of illness at presentation. The city and the hospital environment are foreign to many Aboriginal patients retrieved from remote communities and this adds to the stress of the critical illness. English is a second, third or fourth language for many Aboriginal people from remote communities and strategies must be put in place to ensure informed consent and effective communication are achieved. Despite the increased severity of illness and complexity, the Royal Darwin Hospital ICU achieves the same survival rates for both Aboriginal and non-Aboriginal patients.

Infection with Cryptococcus neoformans is common in the Northern Territory of Australia. Disease is life threatening and treatment is prolonged and often complicated by the need for surgery and difficulties with medical therapy. To document incidence, demography, risk factors, clinical features and outcomes of infection and to determine differences between gattii and neoformans varieties. Case records of all patients (n = 35) diagnosed with cryptococcal infection at the Royal Darwin Hospital between 1976 and 1992 were reviewed retrospectively. Current status of patients was ascertained. Variety identification of isolates was determined by growth in canavanine-glycine-bromthymol blue agar. Of the 35 patients, 23 had meningitis, ten had pneumonia, one had a dermal infection and one had fungaemia with no obvious focus. Twelve (52%) meningitis cases and two (20%) pneumonia cases had no predisposing disease. Thirteen (57%) meningitis cases had concomitant pulmonary cryptococcosis. Twenty-nine patients with Aboriginal and six were Caucasian, with a relative risk for Aboriginals compared with non-Aboriginals of 20.6 (95% CI 8.6-49.5). Arnhemland was the commonest location of infection, with an annual incidence in Aboriginals of 0.14/1000. Fourteen (78%) of 18 isolates tested were C. neoformans var. gattii. Management was characterised by the frequent need for adjunctive surgery and prolonged or repeat courses of systemic antifungal therapy. Despite this, long-term outcomes are encouraging with a mortality of 14% overall and 9% in meningitis patients. The river red gum (Eucalyptus camaldulensis) has a limited distribution in Arnhemland and ongoing studies are seeking alternative environmental sources of C. neoformans var. gattii.

The Darwin Prospective Melioidosis Study (DPMS) commenced on October 1st, 1989. Over 30 years to September 30th, 2019, there were 1148 individuals with Burkholderia pseudomallei culture-positive 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%) First Nations 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 clinical risk factor. Of 1148 primary melioidosis presentations, 1013 (88%) were acute (with an incubation period of 1–21 days, median 4 days, IQR 3–7 days), 106 (9%) were chronic (defined as symptoms for ≥ 2months), and 29 (3%) were considered to be infection activations from latency. 60 (5%) individuals had one or more recurrences of melioidosis, of whom 44 individuals had a relapse and 20 individuals had a new infection, making a total of 1212 episodes of melioidosis over the 30 years. 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 First Nations 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 last 5 years. Genotyping of B. pseudomallei at Menzies School of Health Research evolved from ribotyping in the early days, to pulsed–field gel electrophoresis and BOX–PCR. With the advent of direct genome sequencing, Menzies embraced multilocus sequence typing (MLST) and more recently analysis of whole genome sequencing of B. pseudomallei DNA. Menzies curates the open access global B. pseudomallei MLST website; https://pubmlst.org/organisms/burkholderia-pseudomallei and this, together with shared leadership of the International Melioidosis Network (https://groups.google.com/g/melioidosis) has facilitated long term global collaborations which have informed the emerging understanding of the origins and dynamic global dispersal of B. pseudomallei, both over millennia and in recent years. Of the 1148 primary presentations, we have stored B. pseudomallei isolates and MLST results from 1108 (97%). There were 349 distinct B. pseudomallei sequence types (STs), of which 243 were found only in a single patient. The large diversity of sequence types was especially evident in rural and remote Top End regions. In urban Darwin there was a dynamic situation of persistence throughout the 30 years of common STs 36, 109 and 132, while ST 553 was rare in early years but increased to become the commonest ST in Darwin in the last 5 years. The proliferation of ST 553 is linked to a period of intense urban construction. An evolving story is the likely point source introduction into Darwin of an Asian genotype ST 562, which continues to spread. How this introduction occurred and specifically where from remain to be established. Genotyping has provided important insights into the epidemiology of melioidosis, enabling linking of B. pseudomallei from individual cases to environmental B. pseudomallei recovered from specific potential exposure sites. One notable example is matching a B. pseudomallei genotype from air sampling during stormy weather to the genotype from an individual with presumptive inhalational melioidosis. Case clusters linked to contaminated water supplies have also been confirmed by genotyping. Therapy guidelines for melioidosis have evolved in Darwin over the 3 decades of the DPMS, with local experience informed by a series of randomised comparative antimicrobial trials from Thailand. The revised 2020 Darwin Melioidosis Treatment Guideline is now used nationally and internationally. One conclusion of the DPMS is that melioidosis can be considered analogous to an opportunistic infection. It is very unlikely to kill a healthy person, provided the infection is diagnosed early and resources are available to provide appropriate antibiotics and critical care where required. However, the reality remains that such resources are just not available or are extremely limited in many of the world’s regions where melioidosis is endemic.

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.