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Background In Australia, invasive meningococcal disease (IMD) incidence rapidly increased between 2014 and 2017 due to rising serogroup W (MenW) and MenY infections. We aimed to better understand the genetic diversity of IMD during 2017 and 2018 using whole genome sequencing data. Methods Whole genome sequencing data from 440 Australian IMD isolates collected during 2017 and 2018 and 1737 international MenW:CC11 isolates collected in Europe, Africa, Asia, North America, and South America between 1974 and 2020 were used in phylogenetic analyses; genetic relatedness was determined from single-nucleotide polymorphisms. Results Australian isolates were as follows: 181 MenW (41%), 144 MenB (33%), 88 MenY (20%), 16 MenC (4%), 1 MenW/Y (0.2%), and 10 nongenogroupable (2%). Eighteen clonal complexes (CCs) were identified, and 3 (CC11, CC23, CC41/44) accounted for 78% of isolates (343/440). These CCs were associated with specific serogroups: CC11 (n = 199) predominated among MenW (n = 181) and MenC (n = 15), CC23 (n = 80) among MenY (n = 78), and CC41/44 (n = 64) among MenB (n = 64). MenB isolates were highly diverse, MenY were intermediately diverse, and MenW and MenC isolates demonstrated the least genetic diversity. Thirty serogroup and CC-specific genomic clusters were identified. International CC11 comparison revealed diversification of MenW in Australia. Conclusions Whole genome sequencing comprehensively characterized Australian IMD isolates, indexed their genetic variability, provided increased within-CC resolution, and elucidated the evolution of CC11 in Australia. [ABSTRACT FROM AUTHOR]

Background: Cryptococcus gattii is a globally endemic pathogen causing disease in apparently immune-competent hosts. We describe a 22-year cohort study from Australia's Northern Territory to evaluate trends in epidemiology and management, and outcome predictors. Methods: A retrospective cohort study of all C. gattii infections at the northern Australian referral hospital 1996–2018 was conducted. Cases were defined as confirmed (culture-positive) or probable. Demographic, clinical and outcome data were extracted from medical records. Results: 45 individuals with C. gattii infection were included: 44 Aboriginal Australians; 35 with confirmed infection; none HIV positive out of 38 tested. Multifocal disease (pulmonary and central nervous system) occurred in 20/45 (44%). Nine people (20%) died within 12 months of diagnosis, five attributed directly to C. gattii. Significant residual disability was evident in 4/36 (11%) survivors. Predictors of mortality included: treatment before the year 2002 (4/11 versus 1/34); interruption to induction therapy (2/8 versus 3/37) and end-stage kidney disease (2/5 versus 3/40). Prolonged antifungal therapy was the standard approach in this cohort, with median treatment duration being 425 days (IQR 166–715). Ten individuals had adjunctive lung resection surgery for large pulmonary cryptococcomas (median diameter 6cm [range 2.2-10cm], versus 2.8cm [1.2-9cm] in those managed non-operatively). One died post-operatively, and 7 had thoracic surgical complications, but ultimately 9/10 (90%) treated surgically were cured compared with 10/15 (67%) who did not have lung surgery. Four patients were diagnosed with immune reconstitution inflammatory syndrome which was associated with age <40 years, brain cryptococcomas, high cerebrospinal fluid pressure, and serum cryptococcal antigen titre >1:512. Conclusion: C. gattii infection remains a challenging condition but treatment outcomes have significantly improved over 2 decades, with eradication of infection the norm. Adjunctive surgery for the management of bulky pulmonary C. gattii infection appears to increase the likelihood of durable cure and likely reduces the required duration of antifungal therapy. Author summary: Cryptococcus gattii is an environmental fungus responsible for invasive infection, predominately in the central nervous system (CNS) and lungs. There is little evidence to guide its management. We have found First Nations Australians in this region have one of the highest incidences of Cryptococcus gattii infection in the world, with rates possibly increasing. Mortality was associated with end stage kidney disease, diagnosis in earlier years of the study, and unplanned interruptions to intravenous treatment. Whilst mortality improved through the study, neurological disability such as visual or hearing impairment following cure continues to be seen and is associated with brain cryptococcomas and high cerebral spinal fluid (CSF) pressure at diagnosis or during treatment. Blocked CSF shunts are uncommon and concerns of such potential complications should not preclude necessary surgical intervention for persisting increased CSF opening pressures or hydrocephalus which has been associated with poor outcome. Infection recurrence or persistence was associated with large pulmonary cryptococcomas (over 3cm diameter) not undergoing pulmonary surgery and we recommend that surgery be considered for any pulmonary cryptococcoma with a diameter over 2 to 3cm. Eradication of infection can be expected provided there is adequate therapy but may require very prolonged antifungal treatment. [ABSTRACT FROM AUTHOR]

Background: Acquired zoonotic infections with Pasteurella bacterial species have a wide clinical spectrum of disease from invasive infections to localised bite-wound infections. Methods: This study reviewed the spectrum of the demographic, clinical, temporal, and microbiological trends of laboratory confirmed Pasteurella species infections presenting to a single-centre tropical tertiary hospital over a twenty-year period. Results: 195 episodes from 190 patients were included. 51.3% patients were female, and 20.5% Aboriginal or Torres Strait Islander peoples. Crude incidence of Pasteurella spp. infections increased from 1.5 per 100,000 population in 2000, to 11.4 per 100,000 population in 2021. There were 22 (11.3%) bloodstream infections, 22 (11.3%) invasive, 34 (17.4%) deep local, 98 (50.2%) superficial infections, and 19 (9.7%) other or unknown. Adults over 65 years of age accounted for the majority of bacteraemias (63.7%). More severe infections, including bacteraemia, invasive and deep local infections, were more common in lower limb infections and in those with underlying comorbidities. Animal contact with cats was more common in bloodstream infections (36.4%), but dog bites more common in invasive, deep local and superficial infections. 30-day all-cause mortality was low at 1.0%. Pasteurella multocida was most commonly identified (61.1%), but P. canis, P. dagmatis, and other Pasteurella infections were also noted. 67.7% of specimens were polymicrobial, with other significant organisms being Staphylococcus aureus, Streptococcus pyogenes, Group G Streptococcus and Pseudomonas aeruginosa. Conclusion: Pasteurella species remain clinically important pathogens, with the ability to cause severe and invasive infections with associated morbidity. Presentations to hospital are becoming more common, and the polymicrobial nature of bites wounds has implications for empiric antibiotic guidelines. [ABSTRACT FROM AUTHOR]

Background: A fatal case of Japanese encephalitis (JE) occurred in a resident of the Tiwi Islands, in the Northern Territory of Australia in February 2021, preceding the large JE outbreak in south-eastern Australia in 2022. This study reports the detection, whole genome sequencing and analysis of the virus responsible (designated JEV/Australia/NT_Tiwi Islands/2021). Methods: Reverse transcription quantitative PCR (RT-qPCR) testing was performed on post-mortem brain specimens using a range of JE virus (JEV)-specific assays. Virus isolation from brain specimens was attempted by inoculation of mosquito and mammalian cells or embryonated chicken eggs. Whole genome sequencing was undertaken using a combination of Illumina next generation sequencing methodologies, including a tiling amplicon approach. Phylogenetic and selection analyses were performed using alignments of the Tiwi Islands JEV genome and envelope (E) protein gene sequences and publicly available JEV sequences. Results: Virus isolation was unsuccessful and JEV RNA was detected only by RT-qPCR assays capable of detecting all JEV genotypes. Phylogenetic analysis revealed that the Tiwi Islands strain is a divergent member of genotype IV (GIV) and is closely related to the 2022 Australian outbreak virus (99.8% nucleotide identity). The Australian strains share highest levels of nucleotide identity with Indonesian viruses from 2017 and 2019 (96.7–96.8%). The most recent common ancestor of this Australian-Indonesian clade was estimated to have emerged in 2007 (95% HPD range: 1998–2014). Positive selection was detected using two methods (MEME and FEL) at several sites in the E and non-structural protein genes, including a single site in the E protein (S194N) unique to the Australian GIV strains. Conclusion: This case represents the first detection of GIV JEV acquired in Australia, and only the second confirmed fatal human infection with a GIV JEV strain. The close phylogenetic relationship between the Tiwi Islands strain and recent Indonesian viruses is indicative of the origin of this novel GIV lineage, which we estimate has circulated in the region for several years prior to the Tiwi Islands case. Author summary: A fatal human case of Japanese encephalitis (JE) occurred in a patient from the Tiwi Islands of northern Australia in February 2021. The Tiwi Islands are 80km north of Darwin in the Timor Sea. Attempts to culture the virus from post-mortem brain tissue were unsuccessful. However, the whole genome was successfully sequenced and compared phylogenetically to other JE viruses. The Tiwi Islands strain was shown to belong to the rarely detected genotype IV (GIV) of the JE virus (JEV), together with the Australian 2022 outbreak strain, and is only the second fatal case of JE associated with a GIV virus. JEV strains isolated from Indonesia in 2017 and 2019 were shown to be the most-closely-related to the Australian GIV strain providing evidence for the geographic origins of the emergent Australian virus. From evolutionary analysis, the clade containing the Australian and recent Indonesian viruses was estimated to have emerged between 1998 and 2014, suggesting that this lineage of GIV viruses has been circulating for several years before the Tiwi Islands case. This is the third JE virus genotype to be detected in Australia and demonstrates the ease with which new genotypes can spread and unexpectedly cause disease in new areas. The possible origin and risks of further incursions into Australia are discussed. [ABSTRACT FROM AUTHOR]

Background: There are no national prevalence studies of Strongyloides stercoralis infection in Australia, although it is known to be endemic in northern Australia and is reported in high risk groups such as immigrants and returned travellers. We aimed to determine the seropositivity (number positive per 100,000 of population and percent positive of those tested) and geographical distribution of S. stercoralis by using data from pathology laboratories. Methodology: We contacted all seven Australian laboratories that undertake Strongyloides serological (ELISA antibody) testing to request de-identified data from 2012–2016 inclusive. Six responded. One provided positive data only. The number of people positive, number negative and number tested per 100,000 of population (Australian Bureau of Statistics data) were calculated including for each state/territory, each Australian Bureau of Statistics Statistical Area Level 3 (region), and each suburb/town/community/locality. The data was summarized and expressed as maps of Australia and Greater Capital Cities. Principal findings: We obtained data for 81,777 people who underwent serological testing for Strongyloides infection, 631 of whom were from a laboratory that provided positive data only. Overall, 32 (95% CI: 31, 33) people per 100,000 of population were seropositive, ranging between 23/100,000 (95% CI: 19, 29) (Tasmania) and 489/100,000 population (95%CI: 462, 517) (Northern Territory). Positive cases were detected across all states and territories, with the highest (260-996/100,000 and 17–40% of those tested) in regions across northern Australia, north-east New South Wales and north-west South Australia. Some regions in Greater Capital Cities also had a high seropositivity (112-188/100,000 and 17–20% of those tested). Relatively more males than females tested positive. Relatively more adults than children tested positive. Children were under-represented in the data. Conclusions/Significance: The study confirms that substantial numbers of S. stercoralis infections occur in Australia and provides data to inform public health planning. Author summary: Strongyloides stercoralis, a parasitic roundworm, is endemic in many countries world-wide. In Australia, groups at risk for strongyloidiasis include Aboriginal and/or Torres Strait Islander people, who acquired this parasite locally, and immigrants and returned travellers who acquired the infection outside Australia. We obtained deidentified results of ELISA IgG antibody tests for Strongyloides from diagnostic pathology laboratories during 2012 to 2016 and calculated the number of people who were positive at least once and the number who never had a positive result. We drew maps showing the number positive per 100,000 of population, the percent positive of those tested, and the number tested/100,000 for each region and the number positive in each suburb of residence according to the Australian Bureau of Statistics. The highest seropositivity (260-996/100,000 of population) was in Northern Australia, north-west South Australia and north-east New South Wales where many Aboriginal and Torres Strait Islander people live in remote communities. There were also some regions in Greater Capital Cities with a high number of people positive per 100,000 of population (112-188/100,000), likely reflecting higher populations of immigrants and returned travellers who were infected outside Australia. [ABSTRACT FROM AUTHOR]

The article discusses the results of a comparative study on cases of melioidosis at Royal Darwin Hospital in the 2009-2010 wet season. The researchers compared 91 case of melioidosis in the Top End of the Northern Territory of Australia from October 1, 2009 to September 30, 2010 and postulated reasons for the very high melioidosis incidence. The results show that the prominent increase in melioidosis cases in Darwin is associated with above average rainfall in Darwin.

Burkholderia pseudomallei is the causative agent of melioidosis, a disease highly endemic to Southeast Asia and northern Australia, though the area of endemicity is expanding. Cases may occur in returning travelers or, rarely, from imported contaminated products. Identification of B. pseudomallei is challenging for laboratories that do not see this organism frequently, and misidentifications by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and automated biochemical testing have been reported. The in vitro diagnostic database for use with the Vitek MS has recently been updated to include B. pseudomallei and we aimed to validate the performance for identification in comparison to automated biochemical testing with the Vitek 2 GN card, quantitative real-time polymerase chain reaction (qPCR) targeting the type III secretion system, and capsular polysaccharide antigen detection using a lateral flow immunoassay (LFA). We tested a "derivation" cohort including geographically diverse B. pseudomallei and a range of closely related Burkholderia species, and a prospective "validation" cohort of B. pseudomallei and B. cepacia complex clinical isolates. MALDI-TOF MS had a sensitivity of 1.0 and specificity of 1.0 for the identification and differentiation of B. pseudomallei from related Burkholderia species when a certainty cutoff of 99.9% was used. In contrast, automated biochemical testing for B. pseudomallei identification had a sensitivity of 0.83 and specificity of 0.88. Both qPCR and LFA correctly identified all B. pseudomallei isolates with no false positives. Due to the high level of accuracy, we have now incorporated MALDI-TOF MS into our laboratory's B. pseudomallei identification workflow.IMPORTANCE Burkholderia pseudomallei causes melioidosis, a disease associated with high morbidity and mortality that disproportionately affects rural areas in Southeast Asia and northern Australia. The known area of endemicity is expanding and now includes the continental United States. Laboratory identification can be challenging which may result in missed or delayed diagnoses and poor patient outcomes. In this study, we compared mass spectrometry using an updated spectral database with multiple other methods for B. pseudomallei identification and found mass spectrometry highly accurate. We have therefore incorporated this fast and cost-effective method into our laboratory's workflow for B. pseudomallei identification., Competing Interests: The authors declare no conflict of interest.

Background: Burkholderia pseudomallei, the causative agent of the high-mortality disease melioidosis, is a gram-negative bacterium that is naturally resistant to many antibiotics. There is no vaccine for melioidosis, and effective eradication is reliant on biphasic and prolonged antibiotic administration. The carbapenem drug meropenem is the current gold standard option for treating severe melioidosis. Intrinsic B. pseudomallei resistance toward meropenem has not yet been documented; however, resistance could conceivably develop over the course of infection, leading to prolonged sepsis and treatment failure., Methods: We examined our 30-year clinical collection of melioidosis cases to identify B. pseudomallei isolates with reduced meropenem susceptibility. Isolates were subjected to minimum inhibitory concentration (MIC) testing toward meropenem. Paired isolates from patients who had evolved decreased susceptibility were subjected to whole-genome sequencing. Select agent-compliant genetic manipulation was carried out to confirm the molecular mechanisms conferring resistance., Results: We identified 11 melioidosis cases where B. pseudomallei isolates developed decreased susceptibility toward meropenem during treatment, including 2 cases not treated with this antibiotic. Meropenem MICs increased from 0.5-0.75 µg/mL to 3-8 µg/mL. Comparative genomics identified multiple mutations affecting multidrug resistance-nodulation-division (RND) efflux pump regulators, with concomitant overexpression of their corresponding pumps. All cases were refractory to treatment despite aggressive, targeted therapy, and 2 were associated with a fatal outcome., Conclusions: This study confirms the role of RND efflux pumps in decreased meropenem susceptibility in B. pseudomallei. These findings have important ramifications for the diagnosis, treatment, and management of life-threatening melioidosis cases.

Introduction: Diarrhoeal disease is the second leading cause of death in children under 5 years globally, killing 525 000 annually. Australian Aboriginal and Torres Strait Islander (hereafter Aboriginal) children suffer a high burden of disease. Randomised trials in other populations suggest nitazoxanide accelerates recovery for children with Giardia , amoebiasis, Cryptosporidium, Rotavirus and Norovirus gastroenteritis, as well as in cases where no enteropathogens are found., Methods and Analysis: This double blind, 1:1 randomised, placebo controlled trial is investigating the impact of oral nitazoxanide on acute gastroenteritis in hospitalised Australian Aboriginal children aged 3 months to <5 years. Dosing is based on age-based dosing. The primary endpoint is the time to resolution of 'significant illness' defined as the time from randomisation to the time of clinical assessment as medically ready for discharge, or to the time of actual discharge from hospital, whichever occurs first. Secondary endpoints include duration of hospitalisation, symptom severity during the period of significant illness and following treatment, duration of rehydration and drug safety. Patients will be followed for medically significant events for 60 days. Analysis is based on Bayesian inference. Subgroup analysis will occur by pathogen type (bacteria, virus or parasite), rotavirus vaccination status, age and illness severity., Ethics and Dissemination: Ethics approval has been granted by the Central Australian Human Research Ethics Committee (HREC-14-221) and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC2014-2172). Study investigators will ensure that the trial is conducted in accordance with the principles of the Declaration of Helsinki. Individual participant consent will be obtained. Results will be disseminated via peer-reviewed publication., Trial Registration Number: ACTRN12614000381684., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: 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., Methods: 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™., Results: 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., Conclusions: 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., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

After heavy rains and flooding during early 2011 in the normally arid interior of Australia, melioidosis was diagnosed in 6 persons over a 4-month period. Although the precise global distribution of the causal bacterium Burkholderia pseudomallei remains to be determined, this organism can clearly survive in harsh and even desert environments outside the wet tropics.

Background: The genus Acinetobacter, well known as a nosocomial pathogen, can also cause severe community-onset pneumonia. Previous small case series have suggested fulminant disease and a pooled hospital mortality of > 60%., Methods: We conducted a prospective observational study of all episodes of bacteremic, community-onset, and radiologically confirmed pneumonia due to Acinetobacter species at a tertiary referral hospital in tropical Australia from 1997 to 2012 following the introduction of routine empirical treatment protocols covering Acinetobacter. Demographic, clinical, microbiologic, and outcome data were collected., Results: There were 41 episodes of bacteremic community-onset Acinetobacter pneumonia, of which 36 had no indicators suggesting health-care-associated infection. Of these, 38 (93%) were Indigenous Australians, one-half were men, the average age was 44.1 years, and 36 episodes (88%) occurred during the rainy season. All patients had at least one risk factor, with hazardous alcohol intake in 82%. Of the 37 isolates available for molecular speciation, 35 were Acinetobacter baumannii and two were Acinetobacter nosocomialis. All isolates were susceptible in vitro to gentamicin, meropenem, and ciprofloxacin, but only one was fully susceptible to ceftriaxone. ICU admission was required in 80%. All 41 patients received appropriate antibiotics within the first 24 h of admission, and 28- and 90-day mortality were both low at 11%., Conclusions: Community-acquired Acinetobacter pneumonia is a severe disease, with the majority of patients requiring ICU admission. Most patients have risk factors, particularly hazardous alcohol use. Despite this severity, correct initial empirical antibiotic therapy in all patients was associated with low mortality.

Misidentifications of Burkholderia pseudomallei as Burkholderia cepacia by Vitek 2 have occurred. Multidimensional scaling ordination of biochemical profiles of 217 Malaysian and Australian B. pseudomallei isolates found clustering of misidentified B. pseudomallei isolates from Malaysian Borneo. Specificity of B. pseudomallei identification in Vitek 2 and potentially other automated identification systems is regionally dependent.

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/objective: To characterise the trends in dermatophyte isolation from specimens sourced from metropolitan Melbourne over a 48-year time period., Method: Analysis of submitted specimens from three time periods., Results: Trends identified include: an increasing mean age of the patients; increased numbers of onychomycosis isolates; a significant age difference among patients with Trichophyton interdigitale isolates compared with patients who had other dermatophyte species; and an increasing number of previously rarely isolated imported dermatophytes., Conclusions: Significant shifts are occurring in dermatophyte epidemiology., (© 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.)