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Japanese Encephalitis in AustraliaA patient in whom Japanese encephalitis was diagnosed in February 2021 has been identified as a likely sentinel human case of the 2022 outbreak of the disease in Australia.

Acquired zoonotic infections with Pasteurella bacterial species have a wide clinical spectrum of disease from invasive infections to localised bite-wound infections. 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. 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. 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.

Burkholderia pseudomallei is resistant to most antibiotics. Decreased susceptibility to the reserve antibiotic meropenem would dramatically decrease treatment options. We document the first cases of decreased meropenem susceptibility and identify its molecular basis. Decreased susceptibility was associated with poorer outcomes. Abstract 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.

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. 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. 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. 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.

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. 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. 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. The study confirms that substantial numbers of S. stercoralis infections occur in Australia and provides data to inform public health planning.

Melioidosis is a multisystem disease caused by the sapronotic soil bacterium Burkholderia pseudomallei. Septic arthritis (SA) can occur as either a primary or secondary focus and requires surgical management with prolonged antimicrobial treatment. We used the Darwin Prospective Melioidosis Study to identify patients with melioidosis and SA, filtered by culture confirmation of B. pseudomallei, and subsequently collected synovial fluid analysis, laboratory, clinical, and risk factor data. We identified 68 patients in total with a label of SA, of which 46 patients supplied 69 synovial fluid samples which were culture-positive. These most commonly came from the knee (61%) and ankle (16%), though half (54%) of the specimens were clotted and unable to undergo cell count. We found a median white cell count (WCC) of 63,000 × 106 cells/L in B. pseudomallei culture-positive samples. There was a numerical, but non-significant, difference in median synovial fluid WCC when stratified by preceding antimicrobial use (90,000 × 106 cells/L prior versus 27,800 × 106 cells/L in samples taken post antimicrobial initiation; p = 0.053). One sample was B. pseudomallei culture-positive 32 days following antimicrobial initiation. The presence/absence of contiguous osteomyelitis did not alter synovial fluid white cell counts. These findings suggest that in cases of suspected melioidosis SA, it is not necessary to withhold empirical antimicrobial therapy while awaiting joint aspiration. Further research is needed to define the role of non-culture-based diagnostics in suspected melioidosis SA.

Melioidosis, an infection with the bacterium Burkholderia pseudomallei, is highly endemic in the Top End of the Northern Territory of Australia. The indirect haemagglutination assay (IHA) is the most widely used serology test globally, but it is not standardised among the limited number of laboratories that perform it. While concerns have been raised about the sensitivity of IHA early in melioidosis infections, the advantage of IHA over more recently developed ELISAs is that testing serial dilutions allows a titre to be recorded. While in Australia a titre of 1:40 or higher is considered positive, the specificity at these low positive titres remains uncertain. However, a high titre is considered to represent recent or past true infection with B. pseudomallei, rather than cross-rection with other environmental Burkholderia species. Also, the natural history of IHA titres over time, in both asymptomatic infection and melioidosis has been little studied. We have assessed the clinical status and serology time courses of all 534 patients who had an IHA titre of 1:640 or higher, over a 20-year period. Of these, 324 (60.7%) were diagnosed with culture-confirmed melioidosis, with varying time courses of diagnosis of melioidosis in relation to the high serology. Of the 210 without confirmed melioidosis, 22 (10.5%) were considered highly likely to be melioidosis despite being culture-negative, and these were all treated as melioidosis. In the remainder, titres mostly gradually decreased over time, but the majority remained seropositive. A small number who had not been treated for melioidosis continued to have high IHA titres over years and activation from latency with a new diagnosis of melioidosis was occasionally documented. This study highlights the importance of a full clinical workup in those found to have high titre melioidosis serology as well as subsequent close clinical surveillance and where resources allow, yearly IHA in those not confirmed or treated as melioidosis.

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. 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. 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. 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. The Australian National Health and Medical Research Council.

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). 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. 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. 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.

A traveller returning to Australia developed Zika virus infection, with fever, rash and conjunctivitis, with onset five days after a monkey bite in Bali, Indonesia. Flavivirus RNA detected on PCR from a nasopharyngeal swab was sequenced and identified as Zika virus. Although mosquito-borne transmission is also possible, we propose the bite as a plausible route of transmission. The literature for non-vector transmissions of Zika virus and other flaviviruses is reviewed.