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.

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.

Murray Valley encephalitis virus (MVEV) is the most serious of the endemic arboviruses in Australia. It was responsible for six known large outbreaks of encephalitis in south-eastern Australia in the 1900s, with the last comprising 58 cases in 1974. Since then MVEV clinical cases have been largely confined to the western and central parts of northern Australia. In 2011, high-level MVEV activity occurred in south-eastern Australia for the first time since 1974, accompanied by unusually heavy seasonal MVEV activity in northern Australia. This resulted in 17 confirmed cases of MVEV disease across Australia. Record wet season rainfall was recorded in many areas of Australia in the summer and autumn of 2011. This was associated with significant flooding and increased numbers of the mosquito vector and subsequent MVEV activity. This paper documents the outbreak and adds to our knowledge about disease outcomes, epidemiology of disease and the link between the MVEV activity and environmental factors. Clinical and demographic information from the 17 reported cases was obtained. Cases or family members were interviewed about their activities and location during the incubation period. In contrast to outbreaks prior to 2000, the majority of cases were non-Aboriginal adults, and almost half (40%) of the cases acquired MVEV outside their area of residence. All but two cases occurred in areas of known MVEV activity. This outbreak continues to reflect a change in the demographic pattern of human cases of encephalitic MVEV over the last 20 years. In northern Australia, this is associated with the increasing numbers of non-Aboriginal workers and tourists living and travelling in endemic and epidemic areas, and also identifies an association with activities that lead to high mosquito exposure. This outbreak demonstrates that there is an ongoing risk of MVEV encephalitis to the heavily populated areas of south-eastern Australia.

West Nile virus Kunjin subtype (WNV/KUNV) is enzootic across the tropical north of Australia, with epizootic spread into other jurisdictions. The clinical spectrum of illness in humans is poorly described. We report a clinical case of WNV/KUNV encephalitis and performed a retrospective chart audit of all cases of WNV/KUNV notified in the Northern Territory from 1992 to 2010. Thirteen cases of WNV/KUNV disease were identified; case notes were available for 10 of these presentations. Six of these patients had confirmed infection and presented with neuroinvasive illness, whereas the other four suspect cases comprised three cases with arthralgia, myalgia, and/or rash and one case with fever alone. On the available evidence, WNV/KUNV is of lower virulence compared with the New York 1999 strain. Difficulties in serological diagnosis, especially when paired acute and convalescent sera are not available, may adversely impact the accuracy of the epidemiological and clinical understanding of this virus.

West Nile virus Kunjin subtype (WNV/KUNV) is enzootic across the tropical north of Australia, with epizootic spread into other jurisdictions. The clinical spectrum of illness in humans is poorly described. We report a clinical case of WNV/KUNV encephalitis and performed a retrospective chart audit of all cases of WNV/KUNV notified in the Northern Territory from 1992 to 2010. Thirteen cases of WNV/KUNV disease were identified; case notes were available for 10 of these presentations. Six of these patients had confirmed infection and presented with neuroinvasive illness,whereas the other four suspect cases comprised three cases with arthralgia, myalgia, and/or rash and one case with fever alone. On the available evidence, WNV/KUNV is of lower virulence compared with the New York 1999 strain. Difficulties in serological diagnosis, especially when paired acute and convalescent sera are not available, may adversely impact the accuracy of the epidemiological and clinical understanding of this virus.

BACKGROUND: Neurosyphilis (NS) presents with a variety of clinical syndromes that can be attributed to other aetiologies due to difficulties in its diagnosis. We reviewed all cases of NS from the "Top End" of the Australian Northern Territory over a ten-year period to assess incidence, clinical and laboratory manifestations. METHODS: Patient data (2007-2016) were extracted from hospital records, centralised laboratory data and Northern Territory Centre for Disease Control records. Clinical records of patients with clinically suspected NS were reviewed. A diagnosis of NS was made based on the 2014 US CDC criteria. Results were also recategorized based on the 2018 US CDC criteria. RESULTS: The population of the "Top End" is 185,570, of whom 26.2% are Indigenous. A positive TPPA was recorded in 3126 individuals. A total of 75 (2.4%) of TPPA positive patients had a lumbar puncture (LP), of whom 25 (35%) were diagnosed with NS (9 definite, 16 probable). Dementia was the most common manifestation (58.3%), followed by epilepsy (16.7%), psychosis (12.5%), tabes dorsalis (12.5%) and meningovascular syphilis (8.3%). 63% of probable NS cases were not treated appropriately due to a negative CSF VDRL. Despite increased specificity of the 2018 US CDC criteria, 70% of patient in the probable NS group were not treated appropriately. The overall annual incidence [95%CI] of NS was 2.47[1.28-4.31] per 100 000py in the Indigenous population and 0.95[0.50-1.62] in the non-Indigenous population (rate ratio = 2.60 [1.19-5.70];p = 0.017). CONCLUSION: Neurosyphilis is frequently reported in the NT, particularly in Indigenous populations. Disturbingly, 60% of probable neurosyphilis patients based on the 2014 criteria, and 70% based on the 2018 criteria with were not treated appropriately. It is critical that clinicians should be aware of the diagnosis of NS and treat patients appropriately.

In 2000, investigation into an ulcerative disease in the tails of captive Red Kangaroos (Macropus rufus) resident in the Top End led to the identification of a probable Leishmania species as the cause. The discovery led to some media interest and the concern of the possibility of spread to humans. This article is a very brief overview of human leishmaniasis with the aim of informing health care professionals and the public about this disease and examining the risks to human health in the NT.

Malaria is a notifiable disease in Australia with an average of 600 notifications per year in returned travellers or newly arrived refugees, migrants and visitors. Although endemic disease has been eliminated from the tropical north of Australia, the region remains malaria receptive due to the presence of efficient mosquito vectors. This study analyses enhanced surveillance data collected by the Centre for Disease Control on all cases of malaria notified in the Northern Territory from 1 January 2000 to 31 December 2010. There were 428 malaria episodes notified that occurred in 391 individuals with a median age of 26 years. Of these, 71.4% were male, 40.5% were Australian nationals and 38.0% were prescribed chemoprophylaxis. Primary infection consisted of 196 (51.3%) cases of Plasmodium falciparum, 165 (43.2%) P. vivax, 2 (0.5%) P. ovale, 1 (0.3%) P. malariae and 18 were mixed infections. There were 46 episodes of relapsed infection. Residents of non-malarious countries were most likely to have acquired primary infection in East Timor (40.6%), Papua New Guinea (27.8%), Indonesia (18.7%) and Africa (6.4%). Primary infection was diagnosed after a median 19 days (interquartile range (IQR) 7-69) after arrival in Australia for cases of P. vivax compared with 4 days for P. falciparum (IQR 2-11). Screening protocols led to the diagnosis of 27.2% of cases. Eighty-seven per cent of patients were admitted to hospital at the time of their malaria diagnosis with median duration of 3 days (IQR 2-4) and one patient died. Resettlement of people from endemic countries, as well as military and civilian activities, influences the prevailing notification rates and Plasmodium species type.

To describe the outbreak investigation and control measures for a cluster of measles cases involving 'fly-in fly-out' (FIFO) workers on an off-shore industrial vessel. Following Australian guidelines, measles cases were interviewed and at-risk contacts on the Australian mainland received measles vaccine, immunoglobulin or health advice. For the industrial vessel: (i) exposed FIFO workers who had already left the vessel received health advice through their employer; (ii) workers remaining on the vessel were offered measles vaccine; and (iii) FIFO workers joining the vessel for 21 days following the prodrome onset of the last case of measles on the vessel were offered measles vaccine. Measles virus isolates were sent for genotype determination. Four measles cases from two Australian jurisdictions were epidemiologically linked to the retrospectively identified index case, a New Zealand FIFO worker. No further cases were detected following the institution of outbreak control measures. FIFO workers congregating on large industrial projects are a discrete risk group with the potential to spread infectious diseases over large distances, both domestically and internationally. FIFO workers' immunisation history should be reviewed prior to deployment. Catch-up vaccination, where appropriate, would minimise transmission of vaccine-preventable diseases such as measles and help maintain a healthy, productive workforce.