Mosquitoes as Vectors of Mycobacterium ulcerans Based on Analysis of Notifications of Alphavirus Infection and Buruli Ulcer, Victoria, Australia.

Alphavirus infections are transmitted by mosquitoes, but the mode of transmission for Mycobacterium ulcerans, which causes Buruli ulcer, is contested. Using notification data for Victoria, Australia, during 2017-2022, adjusted for incubation period, we show close alignment between alphavirus and Buruli ulcer seasons, supporting the hypothesis of mosquito transmission of M. ulcerans.

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.

Familial effects account for association between chronic pain and past month smoking.

BACKGROUND: Smoking is associated with chronic pain, but it is not established whether smoking causes pain or if the link is due to familial effects. One proposed mechanism is that smoking strengthens maladaptive cortico-striatal connectivity, which contributes to pain chronification. We leveraged a twin design to assess direct effects of smoking on pain controlling for familial confounds, and whether cortico-striatal connectivity mediates this association. METHODS: In a population-based sample of 692 twins (age = 28.83 years), we assessed past-month smoking frequency (n = 132 used in the past month), presence and severity of a current pain episode (n = 179 yes), and resting-state functional connectivity of the nucleus accumbens and medial prefrontal cortex (NAc-mPFC). RESULTS: Smoking was significantly associated with pain, but the association was not significantly mediated by NAc-mPFC connectivity. In a co-twin control model, smoking predicted which families had more pain but could not distinguish pain between family members. Pain risk was 43% due to additive genetic (A) and 57% due to non-shared environmental (E) influences. Past-month smoking frequency was 71% genetic and 29% non-shared environmental. Smoking and pain significantly correlated phenotypically (r = 0.21, p = 0.001) and genetically (rg = 0.51, p < 0.001), but not environmentally (re = -0.18, p = 0.339). CONCLUSIONS: Pain and smoking are associated; however, the association appears to reflect shared familial risk factors, such as genetic risk, rather than being causal in nature. The connectivity strength of the reward pathway was not related to concurrent pain and smoking in this sample. SIGNIFICANCE: Smoking does not appear to directly cause chronic pain; rather, there may be shared biopsychosocial risk factors, including genetic influences, that explain their association. These findings can be integrated into future research to identify shared biological pathways of both chronic pain and smoking behaviours as a way to conceptualize pain chronification.

An integrated public health response to an outbreak of Murray Valley encephalitis virus infection during the 2022-2023 mosquito season in Victoria.

Introduction: Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus known to cause infrequent yet substantial human outbreaks around the Murray Valley region of south-eastern Australia, resulting in significant mortality. Methods: The public health response to MVEV in Victoria in 2022-2023 included a climate informed pre-season risk assessment, and vector surveillance with mosquito trapping and laboratory testing for MVEV. Human cases were investigated to collect enhanced surveillance data, and human clinical samples were subject to serological and molecular testing algorithms to assess for co-circulating flaviviruses. Equine surveillance was carried out via enhanced investigation of cases of encephalitic illness. Integrated mosquito management and active health promotion were implemented throughout the season and in response to surveillance signals. Findings: Mosquito surveillance included a total of 3,186 individual trapping events between 1 July 2022 and 20 June 2023. MVEV was detected in mosquitoes on 48 occasions. From 2 January 2023 to 23 April 2023, 580 samples (sera and CSF) were tested for flaviviruses. Human surveillance detected 6 confirmed cases of MVEV infection and 2 cases of "flavivirus-unspecified." From 1 September 2022 to 30 May 2023, 88 horses with clinical signs consistent with flavivirus infection were tested, finding one probable and no confirmed cases of MVE. Discussion: The expanded, climate-informed vector surveillance system in Victoria detected MVEV in mosquitoes in advance of human cases, acting as an effective early warning system. This informed a one-health oriented public health response including enhanced human, vector and animal surveillance, integrated mosquito management, and health promotion.

Laboratory evaluation of ELISA and indirect immunofluorescence assay in response to emergence of Japanese encephalitis virus genotype IV in Australia.

The unexpected recent emergence of Japanese encephalitis virus (JEV) genotype IV in multiple southern states of Australia necessitated an evaluation of JEV serological tests suitable for diagnosing acute infection and for seroprevalence studies. This study examined the analytical and clinical performance of two high-throughput JEV assays, Euroimmun immunofluorescence assay (IFA) and Euroimmun enzyme-linked immunosorbent assay (ELISA), across four cohorts; (1) surveillance of piggery workers in outbreak areas, (2) surveillance of residents in outbreak areas, (3) acute JEV infection and (4) post-JEV vaccination. ELISA and IFA IgM demonstrated minimal cross-reactivity (0-1.8%) with other endemic flaviviruses, with high sensitivity (100%) for acute JEV infection in this low endemicity setting. Differences in IgG serodynamics between the two assays suggest convalescent and paired testing with IgM are critical in diagnosing acute infection. High assay concordance was observed between ELISA and IFA when used in serosurveillance (97.4% agreement, Cohen' κ 0.74 [95% CI 0.614-0.860]) and vaccination cohorts (91.1% agreement, Cohen's κ 0.806 [95% CI 0.672-0.941]). In conclusion, this study highlights the clinical & epidemiological applications and limitations of these two commercial JEV assays.

Surveillance for severe influenza and COVID-19 in patients admitted to sentinel Australian hospitals in 2020: the Influenza Complications Alert Network (FluCAN).

Introduction: Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. Coronavirus disease 2019 (COVID-19) is an acute respiratory infection that emerged as a pandemic worldwide before the start of the 2020 Australian influenza season. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza and COVID-19 during the 2020 influenza season in a sentinel surveillance system. Methods: The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Influenza and COVID-19 cases were defined as patients hospitalised at sentinel hospitals and confirmed by nucleic acid detection. Results: There were 448 patients with COVID-19 admitted between 16 March and 31 December 2020, and only 20 patients with influenza admitted between 1 April and 30 November 2020, to one of 22 FluCAN hospitals. Of the COVID-19 cases, 173 (39%) were > 65 years of age, 36 (8%) were children (< 16 years), 6 (1%) were Aboriginal and Torres Strait Islander peoples, 4 (1%) were pregnant and 289 (65%) had chronic comorbidities. COVID-19 hospital admissions peaked between weeks 13 and 15 (first wave) nationally, and again between weeks 31 and 35 (Victoria), with most admissions represented by those above 40 years of age. Discussion: There was an unusually low number of hospital admissions with laboratory-confirmed influenza in this season, compared to recent seasons. This is likely to be due to effective public health interventions and international border closures as a result of a rise in COVID-19 respiratory infections and associated hospitalisations.

Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2019: the Influenza Complications Alert Network (FluCAN).

Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2019 influenza season. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Cases were defined as patients hospitalised at any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data were also collected on a frequency matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 1 April to 31 October 2019 (the 2019 influenza season), there were 4,154 patients admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 44% were elderly (≥ 65 years), 21% were children (< 16 years), 7.7% were Aboriginal and Torres Strait Islander peoples, 1.7% were pregnant and 73% had chronic comorbidities. Most admissions were due to influenza A infection (85%). Estimated vaccine coverage was 75% in the elderly, 49% in non-elderly adults with medical comorbidities, and 27% in young children (< 5 years). The estimated vaccine effectiveness in the target adult population was 42% (95% confidence interval [95% CI]: 36%, 49%). There were a larger number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2019 than in 2018.

Patient satisfaction with a consumer codesigned lower limb cellulitis leaflet.

Objective This study evaluated whether a consumer codesigned leaflet about the common skin infection cellulitis would improve patient satisfaction. Methods A patient information leaflet was codesigned with consumers incorporating health literacy principles and attached to a new adult lower limb cellulitis management plan launched in three regional Victorian health services. Health service staff were educated to provide the leaflet during hospital care. Patients discharged with a diagnosis of cellulitis in an 8-month period were followed-up via telephone between 31 and 60 days after their discharge. Each patient was asked to provide feedback on the utility of the leaflet (if received) and their overall satisfaction with the information provided to them using a five-point scale (with scores of 4 or 5 considered to indicate satisfaction). Results In all, 81 of 127 (64%) patients (or carers) were contactable, consented to the study and answered the questions. Of these, 27% (n = 22) reported receiving, accepting and reading the leaflet. The proportion of patients who were satisfied with the information provided to them about cellulitis was 100% for those who received the leaflet, compared with 78% for those who did not receive the leaflet (95% confidence interval 4.8-34%; P = 0.02). Conclusion The provision of a consumer codesigned leaflet increased patient satisfaction with the information received about cellulitis. Real-world strategies to embed the delivery of such resources are required to ensure that more patients receive the benefit. What is known about the topic? There are known deficiencies in the information provided to patients about the common skin condition cellulitis. There is little published evaluation of strategies to address these knowledge deficiencies. What does this paper add? This study evaluated a simple strategy to address patient knowledge deficiencies on cellulitis. It highlights that pertinent information delivered in an accessible way can significantly increase patient satisfaction with the information provided to them. What are the implications for practitioners? These findings are a timely reminder for practitioners that even a simple intervention, such a providing a hard copy information leaflet, can improve patient satisfaction. A national repository of similar consumer codesigned materials would be valuable and could minimise existing duplication of effort in resource development across health sectors. Real-world strategies to embed the delivery of such resources is required to ensure that more patients receive the benefit.

Prospective international validation of the predisposition, infection, response and organ dysfunction (PIRO) clinical staging system among intensive care and general ward patients.

BACKGROUND: Stratifying patients with sepsis was the basis of the predisposition, infection, response and organ dysfunction (PIRO) concept, an attempt to resolve the heterogeneity in treatment response. The purpose of this study is to perform an independent validation of the PIRO staging system in an international cohort and explore its utility in the identification of patients in whom time to antibiotic treatment is particularly important. METHODS: Prospective international cohort study, conducted over a 6-month period in five Portuguese hospitals and one Australian institution. All consecutive adult patients admitted to selected wards or the intensive care, with infections that met the CDC criteria for lower respiratory tract, urinary, intra-abdominal and bloodstream infections were included. RESULTS: There were 1638 patients included in the study. Patients who died in hospital presented with a higher PIRO score (10 ± 3 vs 8 ± 4, p < 0.001). The observed mortality was 3%, 15%, 24% and 34% in stage I, II, III and IV, respectively, which was within the predicted intervals of the original model, except for stage IV patients that presented a lower mortality. The hospital survival rate was 84%. The application of the PIRO staging system to the validation cohort resulted in a positive predictive value of 97% for stage I, 91% for stage II, 85% for stage III and 66% for stage IV. The area under the receiver operating characteristics curve (AUROC) was 0.75 for the all cohort and 0.70 if only patients with bacteremia were considered. Patients in stage III and IV who did not have antibiotic therapy administered within the desired time frame had higher mortality rate than those who have timely administration of antibiotic. CONCLUSIONS: To our knowledge, this is the first external validation of this PIRO staging system and it performed well on different patient wards within the hospital and in different types of hospitals. Future studies could apply the PIRO system to decision-making about specific therapeutic interventions and enrollment in clinical trials based on disease stage.

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.

Implementation of a Cellulitis Management Plan in Three Australian Regional Health Services to Address an Evidence-Practice Gap in Antibiotic Prescribing.

Despite the availability of evidence-based guidelines, antibiotics for cellulitis remain inappropriately prescribed. This evidence-practice gap is more evident in low-resource settings, such as rural hospitals. This implementation study developed and introduced a cellulitis management plan to improve antibiotic prescribing for cellulitis in three health services in regional Australia. Appropriateness of antibiotic prescribing for cellulitis at Day 1 was the primary outcome measure. Adults with ICD-10-AM codes for lower-limb cellulitis admitted as inpatients of the three health services between May and November 2019 (baseline, n = 165) and March and October 2020 (post-implementation, n = 127) were included in the assessment. The uptake of the cellulitis management plan was 29.1% (37/127). The appropriateness of antibiotic prescribing for cellulitis at Day 1 was similar at baseline (78.7%, 144/183) and in the intention-to-treat post-implementation group (81.8%, 126/154) [95% CI -5.6% to 11.3%, p = 0.50]. Commencement of the cellulitis management plan resulted in a non-statistically significant increase in antibiotic appropriateness at Day 1 compared to when a cellulitis management plan was not commenced (88.1% vs. 79.5%; 95% CI -5.6% to 19.8%; p = 0.20) Evaluation of more real-world strategies to address evidence-practice gaps, such as the appropriateness of antibiotic prescribing for cellulitis, is required.

Antimicrobial stewardship in Australia: the role of qualitative research in programme development.

Antimicrobial stewardship (AMS) in Australia is supported by a number of factors, including enabling national policies, sectoral clinical governance frameworks and surveillance programmes, clinician-led educational initiatives and health services research. A One Health research programme undertaken by the National Centre for Antimicrobial Stewardship (NCAS) in Australia has combined antimicrobial prescribing surveillance with qualitative research focused on developing antimicrobial use-related situational analyses and scoping AMS implementation options across healthcare settings, including metropolitan hospitals, regional and rural hospitals, aged care homes, general practice clinics and companion animal and agricultural veterinary practices. Qualitative research involving clinicians across these diverse settings in Australia has contributed to improved understanding of contextual factors that influence antimicrobial prescribing, and barriers and facilitators of AMS implementation. This body of research has been underpinned by a commitment to supplementing 'big data' on antimicrobial prescribing practices, where available, with knowledge of the sociocultural, technical, environmental and other factors that shape prescribing behaviours. NCAS provided a unique opportunity for exchange and cross-pollination across the human and animal health programme domains. It has facilitated synergistic approaches to AMS research and education, and implementation of resources and stewardship activities. The NCAS programme aimed to synergistically combine quantitative and qualitative approaches to AMS research. In this article, we describe the qualitative findings of the first 5 years.

Barriers to performing onsite COVID-19 testing during the second wave in Victoria: Experiences of general practices.

BACKGROUND AND OBJECTIVES: The approach to performing COVID-19 testing in general practice has been going through an evolution and is variable. The aim of this study was to determine what underlying factors, if any, impeded onsite COVID-19 testing in general practices for patients during the second wave of the pandemic in Victoria. METHOD: This study was conducted during August 2020 and October 2020. Fourteen semi-structured interviews with general practitioners, practice nurses and practice managers were conducted. RESULTS: Barriers to performing onsite testing for COVID-19 were identified as: 1) individual, 2) practitioner perception of fear, 3) lack of personal protective equipment, 4) inappropriate clinic design/location, 5) risk of patient avoidance, 6) financial risk, 7) a lack of knowledge and 8) lack of guidelines. DISCUSSION: This study's findings relate to a unique period in Victoria, which at the time accounted for 70% of the nation's total cases and 90% of deaths. Therefore, the barriers identified in this study may help inform policymakers in regard to planning for future responses to similar situations.

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study.

BACKGROUND: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12. METHODS: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD). PRIMARY RESULTS: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03). CONCLUSIONS: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

Impact of time to first antimicrobial dose on length of stay and 30-day hospital readmission in patients with lower limb cellulitis.

OBJECTIVES: There have been efforts to promote timely antimicrobial administration for patients with sepsis, but the importance for other infections is uncertain. This study analysed whether time to first antimicrobial dose (TFAD) in patients with lower limb cellulitis influenced outcome measures such as acute length of stay (LOS) in hospital and 30-day hospital readmission rates for cellulitis. METHODS: Medical records of patients admitted with lower limb cellulitis or erysipelas over a 15-month period (1 May 2019 to 30 November 2019 and 1 March 2020 to 31 October 2020) were reviewed. Patients requiring intensive care unit (ICU) admission were excluded. The TFAD was the difference (in minutes) between the emergency department triage time and the time that the antimicrobial was first recorded as administered. Analysis included log-transformed linear regression (for LOS) and logistic regression (for 30-day readmission with cellulitis), controlling for confounders where possible. RESULTS: The study included 282 patients with lower limb cellulitis. The median TFAD was 177 min (interquartile range, 98-290 min). Linear regression suggested a weak association between TFAD and LOS (P = 0.05; adjusted R2 = 0.01), which was non-significant after adjusting for confounders (P = 0.18). There were too few patients readmitted within 30 days with cellulitis for meaningful analysis. CONCLUSION: After controlling for confounders, no association between increased TFAD and increased acute LOS was identified for patients with lower limb cellulitis who did not require ICU admission (i.e. without septic shock). Conclusions could not be made for 30-day readmission rates for cellulitis.

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.