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.

The cascade of care for hepatitis C in Victoria, Australia: a data linkage cohort study.

BACKGROUND: Highly effective hepatitis C therapies are available in Australia. However, people living with hepatitis C face various barriers to accessing care and treatment. AIMS: To identify gaps in the cascade of care for hepatitis C and generate estimates of the number living with untreated infection according to population group, using a representative longitudinal study population. METHODS: We linked hepatitis C notification data from Victoria to national pathology, prescribing and death registry data. We assessed receipt of key clinical services in a large cohort who tested positive for hepatitis C from 1 January 2000 to 31 December 2016, with follow-up to 30 June 2018. We estimated the number still living with hepatitis C, adjusting for spontaneous clearance and mortality. RESULTS: The cohort comprised 45 391 people positive for hepatitis C. Of these, 13 346 (29%) received treatment and an estimated 28% (95% confidence interval (CI): 26-30%) were still living with chronic infection at 30 June 2018, with the remainder still living following spontaneous clearance (30%, 95% CI: 29-32%) or having died (12%, 95% CI: 12-12%). Half (50%) of those still living with hepatitis C were born from 1965 to 1980, and 74% first tested positive before 2011. CONCLUSIONS: Despite an enabling policy environment and subsidised therapy, many people in this cohort were not treated. Increased measures may be needed to engage people in care, including those who acquired hepatitis C more than 10 years ago.

Differential Gene Regulation of the Human Blastocyst Trophectoderm and Inner Cell Mass by Progesterone.

Knowledge of action of progesterone (P4) on the human preimplantation embryo is lacking. The objective of this study was to determine expression of a mitochondrial P4 receptor (PR-M) in the trophectoderm (TE) and the inner cell mass (ICM) of the human blastocyst and to determine P4-induced gene expression during growth from the cleavage to the blastocyst stage. Previously cryopreserved cleavage stage embryos were treated with P4 (10-6 M) or vehicle until blastocyst development. Cells from the TE and the ICM of dissected euploid embryos underwent RNA-seq analysis, while other embryos were used for analysis of nuclear PR (nPR) and PR-M expression.PR-M expression was confirmed in the TE, the ICM, and a human embryonic stem cell line (HESC). Conversely, nPR expression was absent in the TE and the ICM with low expression in the HESC line. RNA-seq analysis revealed P4 effects greater in the TE with 183 significant pathway changes compared to 27 in the ICM. The TE response included significant upregulation of genes associated with DNA replication, cell cycle phase transition and others, exemplified by a 7.6-fold increase in the cell proliferation gene, F-Box Associated Domain Containing. The majority of ICM pathways were downregulated including chromosome separation, centromere complex assembly and chromatin remodeling at centromere. This study confirms that human blastocysts express PR-M in both the TE and the ICM, but lack expression of nPR. P4-induced gene regulation differs greatly in the two cell fractions with the predominant effect of cell proliferation in the TE and not the ICM.

SARS-CoV-2 infections and public health responses in schools and early childhood education and care centres in Victoria, Australia: An observational study.

BACKGROUND: The epidemiology of SARS-CoV-2 in children is an important consideration for control measures. To inform the safe re-opening of Victorian schools and early childhood education and care (ECEC) in late 2020, a detailed analysis of local data was undertaken. METHODS: Data on all Victorian SARS-CoV-2 confirmed cases, their close contacts, and ECEC/school events from the first case in Victoria to the end of the third school term (25/01/2020 - 18/09/2020) were analysed. We compared temporal and geographic trends in cases linked to ECEC/school events and community cases; and describe events with onward transmission by age of first case, and public health actions. FINDINGS: Victoria recorded 20,049 SARS-CoV-2 cases during the study period. In total, 1,691 cases and 18,423 contacts were linked to 339 events in ECEC/schools. Many (n=224, 66·1%) events had no evidence of onward transmission, and most (96·5%) involved <10 cases. Onward transmission was more common when the first case was older: when first case was aged 0-5 years, 14·1% events involved additional cases, compared to 30·5% (6-12 years), 33·3% (13-15 years), 42·9% (16-18 years), and 39·1% when the first case was an adult. ECEC/schools were closed within a median of one day (IQR 0-2) from laboratory notification of the first case. INTERPRETATION: Mitigation measures and rapid responses prevented most SARS-CoV-2 cases in ECEC/schools from becoming outbreaks in Victoria in 2020. As new variants emerge and vaccination coverage increases, ECEC/school mitigation strategies should be tailored to local community transmission and educational level. FUNDING: The Victorian Department of Health and Human Services.

Quantifying the rates of late reactivation tuberculosis: a systematic review.

The risk of tuberculosis is greatest soon after infection, but Mycobacterium tuberculosis can remain in the body latently, and individuals can develop disease in the future, sometimes years later. However, there is uncertainty about how often reactivation of latent tuberculosis infection (LTBI) occurs. We searched eight databases (inception to June 25, 2019) to identify studies that quantified tuberculosis reactivation rates occurring more than 2 years after infection (late reactivation), with a focus on identifying untreated study cohorts with defined timing of LTBI acquisition (PROSPERO registered: CRD42017070594). We included 110 studies, divided into four methodological groups. Group 1 included studies that documented late reactivation rates from conversion (n=14) and group 2 documented late reactivation rates in LTBI cohorts from exposure (n=11). Group 3 included 86 studies in LTBI cohorts with an unknown exposure history, and group 4 included seven ecological studies. Since antibiotics have been used to treat tuberculosis, only 11 studies have documented late reactivation rates in infected, untreated cohorts from either conversion (group 1) or exposure (group 2); six of these studies lasted at least 4 years and none lasted longer than 10 years. These studies found that tuberculosis rates declined over time, reaching approximately 200 cases per 100 000 person-years or less by the fifth year, and possibly declining further after 5 years but interpretation was limited by decreasing or unspecified cohort sizes. In cohorts with latent tuberculosis and an unknown exposure history (group 3), tuberculosis rates were generally lower than those seen in groups 1 and 2, and beyond 10 years after screening, rates had declined to less than 100 per 100 000 person-years. Reinfection risks limit interpretation in all studies and the effect of age is unclear. Late reactivation rates are commonly estimated or modelled to prioritise tuberculosis control strategies towards tubuculosis elimination, but significant gaps remain in our understanding that must be acknowledged; the relative importance of late reactivation versus early progression to the global burden of tuberculosis remains unknown.

Periods of altered risk for non-fatal drug overdose: a self-controlled case series.

BACKGROUND: Being recently released from prison or discharged from hospital, or being dispensed opioids, benzodiazepines, or antipsychotics have been associated with an increased risk of fatal drug overdose. This study aimed to examine the association between these periods and non-fatal drug overdose using a within-person design. METHODS: In this self-controlled case series, we used data from the provincial health insurance client roster to identify a 20% random sample of residents (aged ≥10 years) in British Columbia, Canada between Jan 1, 2015, and Dec 31, 2017 (n=921 346). Individuals aged younger than 10 years as of Jan 1, 2015, or who did not have their sex recorded in the client roster were excluded. We used linked provincial health and correctional records to identify a cohort of individuals who had a non-fatal overdose resulting in medical care during this time period, and key exposures, including periods of incarceration, admission to hospital, emergency department care, and supply of medications for opioid use disorder (MOUD), opioids for pain (unrelated to MOUD), benzodiazepines, and antipsychotics. Using a self-controlled case series, we examined the association between the time periods during and after each of these exposures and the incidence of non-fatal overdose with case-only, conditional Poisson regression analysis. Sensitivity analyses included recurrent overdoses and pre-exposure risk periods. FINDINGS: We identified 4149 individuals who had a non-fatal overdose in 2015-17. Compared with unexposed periods (ie, all follow-up time that was not part of a designated risk period for each exposure), the incidence of non-fatal overdose was higher on the day of admission to prison (adjusted incidence rate ratio [aIRR] 2·76 [95% CI 1·51-5·04]), at 1-2 weeks (2·92 [2·37-3·61]), and 3-4 weeks (1·34 [1·01-1·78]) after release from prison, 1-2 weeks after discharge from hospital (1·35 [1·11-1·63]), when being dispensed opioids for pain (after ≥4 weeks) or benzodiazepines (entire use period), and from 3 weeks after discontinuing antipsychotics. The incidence of non-fatal overdose was reduced during use of MOUD (aIRRs ranging from 0·33 [0·26-0·42] to 0·41 [0·25-0·67]) and when in prison (0·12 [0·08-0·19]). INTERPRETATION: Expanding access to and increasing support for stable and long-term medication for the management of opioid use disorder, improving continuity of care when transitioning between service systems, and ensuring safe prescribing and medication monitoring processes for medications that reduce respiratory function (eg, benzodiazepines) could decrease the incidence of non-fatal overdose. FUNDING: Murdoch Children's Research Institute and National Health and Medical Research Council.

The health of adolescents in detention: a global scoping review.

Adolescents detained within the criminal justice system are affected by complex health problems, health-risk behaviours, and high rates of premature death. We did a global synthesis of the evidence regarding the health of this population. We searched Embase, PsycINFO, Education Resources Information Center, PubMed, Web of Science, CINCH, Global Health, the Cochrane Database of Systematic Reviews, the Campbell Library, the National Criminal Justice Reference System Abstract Database, and Google Scholar for peer-reviewed journal articles, including reviews, that reported the prevalence of at least one health outcome (physical, mental, sexual, infectious, and neurocognitive) in adolescents (aged <20 years) in detention, and were published between Jan 1, 1980, and June 30, 2018. The reference lists of published review articles were scrutinised for additional relevant publications. Two reviewers independently screened titles and abstracts, and three reviewed full texts of relevant articles. The protocol for this Review was registered with PROSPERO (CRD42016041392). 245 articles (204 primary research articles and 41 reviews) were included, with most primary research (183 [90%]) done in high-income countries. A high lifetime prevalence of health problems, risks, and conditions was reported in detained adolescents, including mental disorders (0-95%), substance use disorders (22-96%), self-harm (12-65%), neurodevelopmental disabilities (2-47%), infectious diseases (0-34%), and sexual and reproductive conditions (pregnant by age 19 years 20-37%; abnormal cervical screening test result 16%). Various physical and mental health problems and health-risk behaviours are more common among adolescents in detention than among their peers who have not been detained. As the social and structural drivers of poor health overlap somewhat with factors associated with exposure to the criminal justice system, strategies to address these factors could help to reduce both rates of adolescent detention and adolescent health inequalities. Improving the detection of mental and physical disorders, providing appropriate interventions during detention, and optimising transitional health care after release from detention could improve the health outcomes of these vulnerable young people.

Adolescent tuberculosis.

Adolescence is characterised by a substantial increase in the incidence of tuberculosis, a known fact since the early 20th century. Most of the world's adolescents live in low-income and middle-income countries where tuberculosis remains common, and where they comprise a quarter of the population. Despite this, adolescents have not yet been addressed as a distinct population in tuberculosis policy or within tuberculosis treatment services, and emerging evidence suggests that current models of care do not meet their needs. This Review discusses up-to-date information about tuberculosis in adolescence, with a focus on the management of infection and disease, including HIV co-infection and rifampicin-resistant tuberculosis. We outline the progress in vaccine development and highlight important directions for future research.

Emergency health service contact and reincarceration after release from prison: A prospective cohort study.

BACKGROUND: Adults released from prison often have complex health needs. They are at high risk of poor health outcomes and reincarceration, with health service use unlikely to be planned. AIMS/HYPOTHESES: To determine the incidence of emergency health service (EHS) use, ambulance attendance and/or emergency department presentation, among 1,181 adults released from Australian prisons. We hypothesised that EHS contact would be associated with increased reincarceration risk. METHODS: Baseline surveys were conducted within 6 weeks before release. Postrelease EHS contacts and reincarceration were identified through prospective data linkage. For each participant, EHS contacts within a 24-hour period were combined to make an episode. We used Cox proportional hazards regression to examine the relationship between EHS episodes and reincarceration, controlling for covariates. RESULTS: More than half (53.3%) of participants had at least one EHS contact over a median of 25.6-month follow-up. In adjusted analyses, compared to those with no EHS contacts, the hazard of reincarceration was greater for participants who had one to three EHS episodes (hazard ratio [HR] = 1.84; 95% confidence interval [CI] [1.48, 2.29]) or four or more (HR = 2.35; 95% CI [1.67, 3.29]). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Emergency department attendance by people with a history of imprisonment may be indicative of wider decompensation. Improved management of such patients may improve health outcomes and have collateral benefits for reducing reincarceration.

Association Between Antithrombotic Medication Use After Bioprosthetic Aortic Valve Replacement and Outcomes in the Veterans Health Administration System.

Importance: The recommendations about antithrombotic medication use after bioprosthetic aortic valve replacement (bAVR) vary. Objectives: To describe the post-bAVR antithrombotic medication practice across the Veterans Health Administration (VHA) and to assess the association between antithrombotic strategies and post-bAVR outcomes. Design, Setting, and Participants: Retrospective cohort study. Multivariable modeling with propensity scores was conducted to adjust for differences in patient characteristics across the 3 most common antithrombotic medication strategies (aspirin plus warfarin sodium, aspirin only, and dual antiplatelets). Text mining of notes was used to identify the patients with bAVR (fiscal years 2005-2015). Main Outcomes and Measures: This study used VHA and non-VHA outpatient pharmacy data and text notes to classify the following antithrombotic medications prescribed within 1 week after discharge from the bAVR hospitalization: aspirin plus warfarin, aspirin only, dual antiplatelets, no antithrombotics, other only, and warfarin only. The 90-day outcomes included all-cause mortality, thromboembolism risk, and bleeding events. Outcomes were identified using primary diagnosis codes from emergency department visits or hospital admissions. Results: The cohort included 9060 veterans with bAVR at 47 facilities (mean [SD] age, 69.3 [8.8] years; 98.6% male). The number of bAVR procedures per year increased from 610 in fiscal year 2005 to 1072 in fiscal year 2015. The most commonly prescribed antithrombotic strategy was aspirin only (4240 [46.8%]), followed by aspirin plus warfarin (1638 [18.1%]), no antithrombotics (1451 [16.0%]), dual antiplatelets (1010 [11.1%]), warfarin only (439 [4.8%]), and other only (282 [3.1%]). Facility variation in antithrombotic prescription patterns was observed. During the 90-day post-bAVR period, adverse events were uncommon, including all-cause mortality in 127 (1.4%), thromboembolism risk in 142 (1.6%), and bleeding events in 149 (1.6%). No differences in 90-day mortality or thromboembolism were identified across the 3 antithrombotic medication groups in either the unadjusted or adjusted models. Patients receiving the combination of aspirin plus warfarin had higher odds of bleeding than patients receiving aspirin only in the unadjusted analysis (odds ratio, 2.58; 95% CI, 1.71-3.89) and after full risk adjustment (adjusted odds ratio, 1.92; 95% CI, 1.17-3.14). Conclusions and Relevance: These data demonstrate that bAVR procedures are increasingly being performed in VHA facilities and that aspirin only was the most commonly used antithrombotic medication strategy after bAVR. The risk-adjusted results suggest that the combination of aspirin plus warfarin does not improve either all-cause mortality or thromboembolism risk but increases the risk of bleeding events compared with aspirin only.

Cost-utility analysis of low-intensity case management to increase contact with health services among ex-prisoners in Australia.

OBJECTIVES: The economic burden of incarceration is substantial in Australia. People released from prison are at high risk of poor health and this is an important predictor of recidivism. The 'Passports Study' was a randomised controlled trial of an intervention designed to increase health service utilisation after release from prison. The aim of this study is to conduct a cost-utility analysis of this transitional programme. SETTING: Australia DESIGN: A hybrid simulation model was developed to estimate the changes to total economic costs and effectiveness expressed as quality-adjusted life-years (QALYs) from the adoption of the 'Passports' intervention compared with the control group. Model parameters were informed by linked data from Queensland Corrective Services, Medicare, Pharmaceutical Benefits Scheme, Queensland Hospital Admission Patient Data Collection, Emergency Department Information System and National Death Index. Health-related quality of life was measured using the Short-Form 8 Health Survey (SF-8). The primary outcomes were the costs and estimated QALYs associated with the intervention group and the control group. Probabilistic sensitivity analysis was conducted to test parameter uncertainties. RESULTS: Compared with the control group where no attempt was made to encourage health service utilisation, an average participant in the intervention group incurred an extra cost of AUD 1790 and experienced slightly reduced QALYs, which indicated that the intervention was dominated in the baseline analysis. Probabilistic sensitivity analysis revealed that the transitional programme had a low probability of being cost-effective with the outcome measures selected. CONCLUSION: The findings of this study do not provide economic evidence to support the widespread adoption of the Passports intervention. Due to the reductionist nature of the cost-utility approach, it may be that important health-related benefits have been omitted. Another research approach using a wider range of health-related measures might generate different conclusions.

Incidence and prevalence of bacteriologically confirmed pulmonary tuberculosis among adolescents and young adults: a systematic review.

The burden of tuberculosis (TB) among adolescents and young adults in endemic settings is poorly characterised. This study aimed to review published and unpublished estimates of the incidence and prevalence of bacteriologically confirmed TB among young people aged 10-24 years. We searched PubMed and World Health Organization archives for publications and unpublished data from population-based epidemiologic studies reporting confirmed pulmonary TB among young people, conducted from January 2000 onwards. We identified 27 publications and unpublished data from two national surveys, representing a total of 26 studies in 19 countries. The prevalence of bacteriologically confirmed TB ranged from 45 to 799 per 100 000 in the Asia-Pacific region and from 160 to 462 per 100 000 in African settings. We did not identify any epidemiologic studies of confirmed TB among adolescents living with human immunodeficiency virus (HIV). Many studies were excluded due to absent or inadequately reported age-specific data. Adolescents and young adults living in many endemic settings appear to be at substantial risk of developing active TB. There is a pressing need to improve the routine reporting of age in epidemiologic studies of TB, and to generate high-quality epidemiologic data regarding TB among adolescents living with HIV.

Age-Specific Global Prevalence of Hepatitis B, Hepatitis C, HIV, and Tuberculosis Among Incarcerated People: A Systematic Review.

PURPOSE: This study aims to compare the global prevalence of hepatitis B, hepatitis C, HIV, and tuberculosis in incarcerated adolescents and young adults (AYAs) and older prisoners. METHODS: This study is a systematic review and meta-analysis of studies reporting the age-specific prevalence of each infection in prisoners. We grouped age-specific prevalence estimates into three overlapping age categories: AYA prisoners (<25 years), older prisoners (≥25 years), and mixed category (spanning age 25 years). We used random effects meta-analysis to estimate the relative risk (RR) of each infection in AYAs versus older prisoners. RESULTS: Among 72 studies, there was marked heterogeneity in prevalence estimates among AYA prisoners for all infections: hepatitis B (.4%-25.2%), hepatitis C (.0%-70.6%), HIV (.0%-15.8%), and active tuberculosis (.0%-3.7%). The pooled prevalence of HIV (RR = .39, 95% confidence interval .29-.53, I2 = 79.2%) and hepatitis C (RR = .51, 95% confidence interval .33-.78, I2 = 97.8%) was lower in AYAs than in older prisoners. CONCLUSIONS: The prevalence of HIV and hepatitis C is lower in AYA prisoners than in older prisoners. Despite lower prevalence, acquisition begins early among incarcerated populations. There is an urgent need for targeted, age-appropriate prevention, treatment, and harm reduction measures in and beyond custodial settings to reduce the incidence of infection in these extremely vulnerable young people.

The incidence of tuberculosis among adolescents and young adults: a global estimate.

Historical data show that the risk of tuberculosis increases dramatically during adolescence, and young people face unique challenges in terms of case detection and effective treatment. However, little is known about the burden of tuberculosis among young people in the modern era. This study aimed to provide the first estimates of the global and regional incidence of tuberculosis among young people aged 10-24 years.Using the World Health Organization (WHO) database of tuberculosis notifications for 2012, we estimated the burden of tuberculosis among young people by WHO region. Adjustments were made for incomplete age disaggregation and underreporting, using supplementary data from several countries representing diverse tuberculosis epidemics.We estimate that 1.78 million (uncertainty interval (UI) 1.23-3.00 million) young people developed tuberculosis in 2012, accounting for 17% of all new tuberculosis cases globally. Young people in the WHO South East Asian Region (721 000, UI 473 000-1.35 million) and the WHO African Region (534 000, UI 359 000-912 000) experienced the greatest number of tuberculosis episodes.Young people suffer a considerable burden of tuberculosis. Age-specific burden of disease estimation for this age group is complicated by incomplete age disaggregation of tuberculosis data, highlighting the importance of continued surveillance system strengthening.

Correction to: The impact of drug resistance on the risk of tuberculosis infection and disease in child household contacts: a cross sectional study.

After publication of the original article [1] the authors noted that the following errors had occurred.