Serosurvey for Japanese encephalitis virus antibodies following an outbreak in an immunologically naïve population, Victoria, 2022: a cross-sectional study.

OBJECTIVES: To investigate the distribution and prevalence of Japanese encephalitis virus (JEV) antibody (as evidence of past infection) in northern Victoria following the 2022 Japanese encephalitis outbreak, seeking to identify groups of people at particular risk of infection; to investigate the distribution and prevalence of antibodies to two related flaviviruses, Murray Valley encephalitis virus (MVEV) and West Nile virus Kunjin subtype (KUNV). STUDY DESIGN: Cross-sectional serosurvey (part of a national JEV serosurveillance program). SETTING: Three northern Victorian local public health units (Ovens Murray, Goulburn Valley, Loddon Mallee), 8 August - 1 December 2022. PARTICIPANTS: People opportunistically recruited at pathology collection centres and by targeted recruitment through community outreach and advertisements. People vaccinated against or who had been diagnosed with Japanese encephalitis were ineligible for participation, as were those born in countries where JEV is endemic. MAIN OUTCOME MEASURES: Seroprevalence of JEV IgG antibody, overall and by selected factors of interest (occupations, water body exposure, recreational activities and locations, exposure to animals, protective measures). RESULTS: 813 participants were recruited (median age, 59 years [interquartile range, 42-69 years]; 496 female [61%]); 27 were JEV IgG-seropositive (3.3%; 95% confidence interval [CI], 2.2-4.8%) (median age, 73 years [interquartile range, 63-78 years]; 13 female [48%]); none were IgM-seropositive. JEV IgG-seropositive participants were identified at all recruitment locations, including those without identified cases of Japanese encephalitis. The only risk factors associated with JEV IgG-seropositivity were age (per year: prevalence odds ratio [POR], 1.07; 95% CI, 1.03-1.10) and exposure to feral pigs (POR, 21; 95% CI, 1.7-190). The seroprevalence of antibody to MVEV was 3.0% (95% CI, 1.9-4.5%; 23 of 760 participants), and of KUNV antibody 3.3% (95% CI, 2.1-4.8%; 25 of 761). CONCLUSIONS: People living in northern Victoria are vulnerable to future JEV infection, but few risk factors are consistently associated with infection. Additional prevention strategies, including expanding vaccine eligibility, may be required to protect people in this region from Japanese encephalitis.

Correlation between Buruli Ulcer Incidence and Vectorborne Diseases, Southeastern Australia, 2000-2020.

Researchers have hypothesized that mosquitoes are vectors involved in Mycobacterium ulcerans transmission. Previous findings of a correlation between incidence of M. ulcerans, which causes Buruli ulcer, and locally acquired vectorborne diseases in southeastern Australia further strengthened this argument. However, our updated data indicate that this correlation has not continued beyond 2008.

Bittersweet: infective complications of drug-induced glycosuria in patients with diabetes mellitus on SGLT2-inhibitors: two case reports.

BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor. CASE PRESENTATIONS: Both cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased. CONCLUSIONS: Despite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in these cases. Clinicians should be aware of their mechanism of action and associated risk of infection and prior to prescription, assessment of urogenital anatomical abnormalities should be performed to identify patients who may be at risk of complicated infection.

Six vs Eight Weeks of Antibiotics for Small Mycobacterium ulcerans Lesions in Australian Patients.

BACKGROUND: Antibiotics are highly effective in curing Mycobacterium ulcerans lesions, but are associated with significant toxicity. In those not undergoing surgery, we compared 6 weeks with the currently recommended 8 weeks of combination antibiotic therapy for small M. ulcerans lesions. METHODS: Mycobacterium ulcerans cases from an observational cohort at Barwon Health, Victoria, treated with antibiotics alone from 1 October 2010 to 31 March 2018 were included. The 6-week antibiotic group received ≥28 days and ≤42 days and the 8-week antibiotic group received ≥56 days of antibiotic therapy, respectively. Only World Health Organization category 1 lesions were included. RESULTS: 207 patients were included; 53 (25.6%) in the 6-week group and 154 (74.4%) in the 8-week group. The median age of patients was 53 years (interquartile range [IQR], 33-69 years) and 100 (48.3%) were female. Lesions were ≤900 mm2 in size in 79.7% of patients and 93.2% were ulcerative. Fifty-three patients (100%) achieved treatment cure in the 6-week group compared with 153 (99.4%) in the 8-week group (P = .56). No patients died or were lost to follow-up during the study. Median time to heal was 70 days (IQR, 60-96 days) in the 6-week group and 128 days (IQR, 95-173 days) in the 8-week group (P < .001). Two (3.8%) patients in the 6-week group experienced a paradoxical reaction compared with 39 (25.3%) patients in the 8-week group (P = .001). CONCLUSIONS: For selected small M. ulcerans lesions, 6 weeks may be as effective as 8 weeks of combined antibiotic therapy in curing lesions without surgery.

Risk Factors Associated with Antibiotic Treatment Failure of Buruli Ulcer.

Combination antibiotic therapy is highly effective in curing Buruli ulcer (BU) caused by Mycobacterium ulcerans Treatment failures have been uncommonly reported with the recommended 56 days of antibiotics, and little is known about risk factors for treatment failure. We analyzed treatment failures among BU patients treated with ≥56 days of antibiotics from a prospective observational cohort at Barwon Health, Victoria, from 1 January 1998 to 31 December 2018. Treatment failure was defined as culture-positive recurrence within 12 months of commencing antibiotics under the following conditions: (i) following failure to heal the initial lesion or (ii) a new lesion developing at the original or at a new site. A total of 430 patients received ≥56 days of antibiotic therapy, with a median duration of 56 days (interquartile range [IQR], 56 to 80). Seven (1.6%) patients experienced treatment failure. For six adult patients experiencing treatment failure, all were male, weighed >90 kg, did not have surgery, and received combination rifampin-clarithromycin (median rifampin dose, 5.6 mg per kg of body weight per day; median clarithromycin dose, 8.1 mg/kg/day). When compared to those who did not fail treatment on univariate analysis, treatment failure was significantly associated with a weight of >90 kg (P < 0.001), male gender (P = 0.02), immune suppression (P = 0.04), and a first-line regimen of rifampin-clarithromycin compared to a regimen of rifampin-fluoroquinolone (P = 0.05). There is a low rate of treatment failure in Australian BU patients treated with rifampin-based oral combination antibiotic therapy. Our study raises the possibility that treatment failure risk may be increased in males, those with a body weight of >90 kg, those with immune suppression, and those taking rifampin-clarithromycin antibiotic regimens, but future pharmacokinetic and pharmacodynamics studies are required to determine the validity of these hypotheses.

Identification of hospitalized patients with community-acquired infection in whom treatment guidelines do not apply: a validated model.

OBJECTIVES: To develop and validate a clinical model to identify patients admitted to hospital with community-acquired infection (CAI) caused by pathogens resistant to antimicrobials recommended in current CAI treatment guidelines. METHODS: International prospective cohort study of consecutive patients admitted with bacterial infection. Logistic regression was used to associate risk factors with infection by a resistant organism. The final model was validated in an independent cohort. RESULTS: There were 527 patients in the derivation and 89 in the validation cohort. Independent risk factors identified were: atherosclerosis with functional impairment (Karnofsky index <70) [adjusted OR (aOR) (95% CI) = 2.19 (1.41-3.40)]; previous invasive procedures [adjusted OR (95% CI) = 1.98 (1.28-3.05)]; previous colonization with an MDR organism (MDRO) [aOR (95% CI) = 2.67 (1.48-4.81)]; and previous antimicrobial therapy [aOR (95% CI) = 2.81 (1.81-4.38)]. The area under the receiver operating characteristics (AU-ROC) curve (95% CI) for the final model was 0.75 (0.70-0.79). For a predicted probability ≥22% the sensitivity of the model was 82%, with a negative predictive value of 85%. In the validation cohort the sensitivity of the model was 96%. Using this model, unnecessary broad-spectrum therapy would be recommended in 30% of cases whereas undertreatment would occur in only 6% of cases. CONCLUSIONS: For patients hospitalized with CAI and none of the following risk factors: atherosclerosis with functional impairment; previous invasive procedures; antimicrobial therapy; or MDRO colonization, CAI guidelines can safely be applied. Whereas, for those with some of these risk factors, particularly if more than one, alternative antimicrobial regimens should be considered.

Junior doctor training: has the pendulum swung too far?

The current Australian Medical Association doctors in training enterprise agreement dictates that hours beyond 38 or 43 ordinary hours per week incur overtime. Costly overtime has led to strict adherence to ordinary hours with dramatically reduced rostered and unrostered overtime. The stringent regulation over ordinary hours may protect doctors at a cost to training and potentially patient safety. Reduced shift duration adds to the number of clinical handovers, while reduced exposure to patients and training opportunities may prolong training time. Now is the time for renegotiation of working hours, which are most favourable for doctor training and well-being.

Increased Severity and Spread of Mycobacterium ulcerans, Southeastern Australia.

Reported cases of Mycobacterium ulcerans disease (Buruli ulcer) have been increasing in southeastern Australia and spreading into new geographic areas. We analyzed 426 cases of M. ulcerans disease during January 1998-May 2017 in the established disease-endemic region of the Bellarine Peninsula and the emerging endemic region of the Mornington Peninsula. A total of 20.4% of cases-patients had severe disease. Over time, there has been an increase in the number of cases managed per year and the proportion associated with severe disease. Risk factors associated with severe disease included age, time period (range of years of diagnosis), and location of lesions over a joint. We highlight the changing epidemiology and pathogenicity of M. ulcerans disease in Australia. Further research, including genomic studies of emergent strains with increased pathogenicity, are urgently needed to improve the understanding of disease to facilitate implementation of effective public health measures to halt its spread.

What makes a good doctor?

What makes a good doctor probably depends on whom you ask. Patients value interpersonal relations, and being involved in decisions about their care. In contrast, hospital executives place an emphasis on the ability to meet key performance indicators critical to the flow of patients through hospitals.

Recording patient bodyweight in hospitals: are we doing well enough?

Recording patient weight is a standard practice for all hospital admissions, with this measurement influencing other daily practices that rely on the delivery of safe and effective patient care. Patient weight is important in the areas of medication prescribing, fluid balance and assessment of nutrition. In particular, prescribing narrow therapeutic index medications may result in significant harm as a potential consequence of inaccurate dosing. Despite its importance, it is evident that bodyweight measurements are recorded in only 13.5-55% of hospital patients, in a variety of settings including the emergency department, intensive care unit, medical and surgical wards. Barriers to compliance of healthcare staff include additional workload, patient handling and availability of appropriate weighing equipment. Hospitals and patients would benefit from enhancing compliance with the systematic weighing of patients, staff training and removing barriers to performing this task.

Exposure Risk for Infection and Lack of Human-to-Human Transmission of Mycobacterium ulcerans Disease, Australia.

We conducted epidemiologic and genetic analyses of family clusters of Mycobacterium ulcerans (Buruli ulcer) disease in southeastern Australia. We found that the incidence of M. ulcerans disease in family members was increased. However, the risk for exposure appeared short-term and not related to human-human transmission.

Community-acquired syndromes causing morbidity and mortality in Australia
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INTRODUCTION: The clinical and economic burden of infectious diseases is a substantial public health problem. The determination of the relative contributions of these diseases to the overall healthcare burden can inform priority setting, planning, and decision-making in healthcare and establish a baseline for future comparisons. Few recent studies have presented definitive data on the incidence of infectious diseases requiring hospitalisation in the Southern Hemisphere. We identified the age-specific number of hospitalisations and severe infections requiring intensive care unit admissions in the Geelong region. This was then extrapolated to calculate incidence data of these selected infectious diseases in Australia.
 Methods: This observational study was performed in Geelong, the second largest city in Victoria (population of 194,566 adults ≥ 20 years). University Hospital Geelong is a public hospital with the only emergency department in Geelong during the years 2011 and 2013. Patients were identified using the International Classification of Diseases, 10th Revision Australian Modification discharge codes and diagnoses were confirmed using clinical, radiological and laboratory criteria.
 Results: Between 2011 and 2013, there were 1,506 admissions for community-acquired pneumonia (CAP) (245.3 per 100,000 person years), 1,613 admissions for skin and soft tissue infections (SSTIs) (271.2 per 100,000 person years), 479 for pyelonephritis (79.7 per 100,000 person years), 131 for influenza (22.4 per 100,000 person years), and 52 for meningitis (8.9 per 100,000 person years).
 Conclusion: SSTI, CAP, and pyelonephritis are common syndromes responsible for admission to hospital in Australia, with an incidence that increases with age. CAP is a major cause of morbidity and mortality in the Australian population. Influenza is associated with the greatest percentage of severe infections requiring intensive care unit admission.

Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2016: the Influenza Complications Alert Network (FluCAN).

During the period 1 April to 30 October 2016 (the 2016 influenza season), 1,952 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 46% were elderly (e65 years), 18% were children (<16 years), 5% were Aboriginal and Torres Strait Islander peoples, 3% were pregnant and 76% had chronic co-morbidities.

Increasing Experience with Primary Oral Medical Therapy for Mycobacterium ulcerans Disease in an Australian Cohort.

Buruli ulcer (BU) is a necrotizing infection of subcutaneous tissue that is caused by Mycobacterium ulcerans and is responsible for disfiguring skin lesions. The disease is endemic to specific geographic regions in the state of Victoria in southeastern Australia. Growing evidence of the effectiveness of antibiotic therapy for M. ulcerans disease has evolved our practice to the use of primarily oral medical therapy. An observational cohort study was performed on all confirmed M. ulcerans cases treated with primary rifampin-based medical therapy at Barwon Health between October 2010 and December 2014 and receiving 12 months of follow-up. One hundred thirty-two patients were managed with primary medical therapy. The median age of patients was 49 years, and nearly 10% had diabetes mellitus. Lesions were ulcerative in 83.3% of patients and at WHO stage 1 in 78.8% of patients. The median duration of therapy was 56 days, with 22 patients (16.7%) completing fewer than 56 days of antimicrobial treatment. Antibiotic-associated complications requiring cessation of one or more antibiotics occurred in 21 (15.9%) patients. Limited surgical debridement was performed on 30 of these medically managed patients (22.7%). Cure was achieved, with healing within 12 months, in 131 of 132 patients (99.2%), and cosmetic outcomes were excellent. Primary rifampin-based oral medical therapy for M. ulcerans disease, combined with either clarithromycin or a fluoroquinolone, has an excellent rate of cure and an acceptable toxicity profile in Australian patients. We advocate for further research to determine the optimal and safest minimum duration of medical therapy for BU.

Diabetic foot infection in hospitalized adults.

BACKGROUND: Acute infections of the diabetic foot (DFI) are a common and complex condition. Patients are generally managed in the ambulatory setting and epidemiological data pertaining to hospitalized patients is lacking. The aim of this study was to analyze the epidemiology, microbiology and outcomes of hospitalized patients with DFI, who are managed at a referral center equipped with hyperbaric oxygen (HBO) therapy. METHODS: A retrospective cohort study of adult patients admitted to a tertiary referral center with DFI over a six-month period in 2013 was undertaken. Predictors of clinical outcomes and efficacy of treatment modalities were analyzed by Cox regression. RESULTS: Sixty-one patients with DFI were identified. Most patients were elderly (67 ± 13 years), with long-standing (17 ± 9 years), poorly controlled (HbA1c 9 ± 3%) diabetes. Most patients had polymicrobial infection (80%); specifically, anaerobic (39%) and multi or extensively-drug resistant organisms (61%). Administration of appropriate antimicrobials was delayed for >48 h in 83%. Advanced age was associated with worse outcomes. Sicker patients with severe peripheral vascular disease were managed with HBO. The use of HBO was associated with higher costs and increased functional deterioration, and did not prevent future limb amputation. CONCLUSIONS: Our study illustrates the descriptive epidemiology of hospitalized adults with DFI predominantly of polymicrobial etiology. MDROs and anaerobic organisms are common causative pathogens, and appropriate antibiotics were frequently delayed. HBO treatment may delay the need for limb amputation, but not obviate this eventual outcome.

Influenza epidemiology, vaccine coverage and vaccine effectiveness in children admitted to sentinel Australian hospitals in 2014: the Influenza Complications Alert Network (FluCAN).

The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance programme operating in all states and territories in Australia. We summarise the epidemiology of children hospitalised with laboratory-confirmed influenza in 2014 and reports on the effectiveness of inactivated trivalent inactivated vaccine (TIV) in children. In this observational study, cases were defined as children admitted with acute respiratory illness (ARI) with influenza confirmed by PCR. Controls were hospitalised children with ARI testing negative for influenza. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio of vaccination in influenza positive cases compared with test-negative controls using conditional logistic regression models. From April until October 2014, 402 children were admitted with PCR-confirmed influenza. Of these, 28% were aged < 1 year, 16% were Indigenous, and 39% had underlying conditions predisposing to severe influenza. Influenza A was detected in 90% of cases of influenza; influenza A(H1N1)pdm09 was the most frequent subtype (109/141 of subtyped cases) followed by A(H3N2) (32/141). Only 15% of children with influenza received antiviral therapy. The adjusted VE of one or more doses of TIV for preventing hospitalised influenza was estimated at 55.5% (95% confidence intervals (CI): 11.6-77.6%). Effectiveness against influenza A(H1N1)pdm09 was high (91.6% , 95% CI: 36.0-98.9%) yet appeared poor against H3N2. In summary, the 2014 southern hemisphere TIV was moderately effective against severe influenza in children. Significant VE was observed against influenza A(H1N1)pdm09.

Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2015: the Influenza Complications Alert Network.

The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2015 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals with an acute respiratory illness with influenza confirmed by nucleic acid detection. During the period 1 April to 30 October 2015 (the 2015 influenza season), 2,070 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 46% were elderly (≥ 65 years), 15% were children (< 16 years), 5% were Indigenous Australians, 2.1% were pregnant and 75% had chronic co-morbidities. A high proportion were due to influenza B (51%). There were a large number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2015 with case numbers similar to that reported in 2014. The national immunisation program is estimated to avert 46% of admissions from confirmed influenza across all at-risk groups, but more complete vaccination coverage in target groups could further reduce influenza admissions by as much as 14%.

Rapid evolution of elaborate male coloration is driven by visual system in Australian fairy-wrens (Maluridae).

The interplay between colour vision and animal signalling is of keen interest to behavioural ecologists and evolutionary biologists alike, but is difficult to address in terrestrial animals. Unlike most avian lineages, in which colour vision is relatively invariant among species, the fairy-wrens and allies (Maluridae) show a recent gain of ultraviolet sensitivity (UVS). Here, we compare the rates of colour evolution on 11 patches for males and females across Maluridae in the context of their visual system. We measured reflectance spectra for 24 species, estimating five vision-independent colour metrics as well as metrics of colour contrast among patches and sexual dichromatism in a receiver-neutral colour space. We fit Brownian motion (BM) and Ornstein-Uhlenbeck (OU) models to estimate evolutionary rates for these metrics and to test whether male coloration, female coloration or dichromatism was driven by selective regimes defined by visual system or geography. We found that in general male coloration evolved rapidly in comparison with females. Male colour contrast was strongly correlated with visual system and expanded greatly in UVS lineages, whereas female coloration was weakly associated with geography (Australia vs. Papua New Guinea). These results suggest that dichromatism has evolved in Maluridae as males and females evolve at different rates, and are driven by different selection pressures.

Influenza epidemiology in adults admitted to sentinel Australian hospitals in 2014: the Influenza Complications Alert Network (FluCAN).

The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2014 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals with an acute respiratory illness with influenza confirmed by nucleic acid detection. During the period 3 April to 31 October 2014 (the 2014 influenza season), 1,692 adult patients (>16 years) were admitted with confirmed influenza to one of 15 of 17 FluCAN sentinel hospitals (excluding 2 paediatric hospitals). Of these, 47% were over 65 years of age, 10% were Indigenous Australians, 3.3% were pregnant and 85% had chronic co-morbidities. The majority of cases were due to influenza A. Influenza B was detected in 7% of patients. There were a large number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2014. These are estimated to represent a national annual burden of around 15,000 admissions and almost 100,000 bed-days nationally.