Characterizing Traumatic Brain Injury and Its Association with Losing Stable Housing in a Community-based Sample.

OBJECTIVE: Traumatic brain injury (TBI) is increasingly recognized as a common and impactful health determinant in homeless and precariously housed populations. We sought to describe the history of TBI in a precariously housed sample and evaluate how TBI was associated with the initial loss and lifetime duration of homelessness and precarious housing. METHOD: We characterized the prevalence, mechanisms, and sex difference of lifetime TBI in a precariously housed sample. We also examined the impact of TBI severity and timing on becoming and staying homeless or precariously housed; 285 precariously housed participants completed the Brain Injury Screening Questionnaire in addition to other health assessments. RESULTS: A history of TBI was reported in 82.1% of the sample, with 64.6% reporting > 1 TBI, and 21.4% reporting a moderate or severe TBI. Assault was the most common mechanism of injury overall, and females reported significantly more traumatic brain injuries due to physical abuse than males (adjusted OR = 1.26, 95% CI = 1.14 to 1.39, P < 0.0001). The first moderate or severe TBI was significantly closer to the first experience of homelessness (b = 2.79, P = 0.003) and precarious housing (b = 2.69, P < 0.0001) than was the first mild TBI. In participants who received their first TBI prior to becoming homeless or precariously housed, traumatic brain injuries more proximal to the initial loss of stable housing were associated with a longer lifetime duration of homelessness (RR = 1.04, 95% CI = 1.02 to 1.06, P < 0.0001) and precarious housing (RR = 1.03, 95% CI = 1.01 to 1.04, P < 0.0001). CONCLUSIONS: These findings demonstrate the high prevalence of TBI in this vulnerable population, and that aspects of TBI severity and timing are associated with the loss and lifetime duration of stable housing.

Revisiting the Importance of Orthobunyaviruses for Animal Health: A Scoping Review of Livestock Disease, Diagnostic Tests, and Surveillance Strategies for the Simbu Serogroup.

Orthobunyaviruses (order Bunyavirales, family Peribunyaviridae) in the Simbu serogroup have been responsible for widespread epidemics of congenital disease in ruminants. Australia has a national program to monitor arboviruses of veterinary importance. While monitoring for Akabane virus, a novel orthobunyavirus was detected. To inform the priority that should be given to this detection, a scoping review was undertaken to (1) characterise the associated disease presentations and establish which of the Simbu group viruses are of veterinary importance; (2) examine the diagnostic assays that have undergone development and validation for this group of viruses; and (3) describe the methods used to monitor the distribution of these viruses. Two search strategies identified 224 peer-reviewed publications for 33 viruses in the serogroup. Viruses in this group may cause severe animal health impacts, but only those phylogenetically arranged in clade B are associated with animal disease. Six viruses (Akabane, Schmallenberg, Aino, Shuni, Peaton, and Shamonda) were associated with congenital malformations, neurological signs, and reproductive disease. Diagnostic test interpretation is complicated by cross-reactivity, the timing of foetal immunocompetence, and sample type. Serological testing in surveys remains a mainstay of the methods used to monitor the distribution of SGVs. Given significant differences in survey designs, only broad mean seroprevalence estimates could be provided. Further research is required to determine the disease risk posed by novel orthobunyaviruses and how they could challenge current diagnostic and surveillance capabilities.

Optimising the Delivery of RHDV to Rabbits for Biocontrol: An Experimental Evaluation of Two Novel Methods of Virus Delivery.

Rabbit haemorrhagic disease virus (RHDV) is established as a landscape-scale biocontrol that assists the management of invasive European rabbits and their impacts in both Australia and New Zealand. In addition to this, it is also available to land managers to augment rabbit control efforts at a local scale. However, current methods of deploying RHDV to rabbits that rely on the consumption of virus-treated baits can be problematic as rabbits are reluctant to consume bait when there is abundant, green, protein-rich feed available. We ran a suite of interrupted time-series experiments to compare the duration of infectivity of two conventional (carrot and oat baits) and two novel (meat bait and soil burrow spray) methods of deploying RHDV to rabbits. All methods effectively killed exposed rabbits. Soil burrow spray and carrot baits resulted in infection and mortality out to 5 days post their deployment in the field, and meat baits caused infection out to 10 days post their deployment. In contrast, oat baits continued to infect and kill exposed rabbits out to 20 days post deployment. Molecular assays demonstrated high viral loads in deployed baits beyond the duration for which they were infectious or lethal to rabbits. Based on our results, we suggest that the drying of meat baits may create a barrier to effective transmission of RHDV by adult flies within 10 days. We therefore hypothesise that fly larvae production and development on infected tissues is critical to prolonged viral transmission from meat baits, and similarly from carcasses of RHDV mortalities, via mechanical fly vectors. Our study demonstrates that meat baits and soil spray could provide additional virus deployment options that remove the need for rabbits to consume baits at times when they are reluctant to do so.

Utilizing Molecular Epidemiology and Citizen Science for the Surveillance of Lagoviruses in Australia.

Australia has multiple lagoviruses with differing pathogenicity. The circulation of these viruses was traditionally determined through opportunistic sampling events. In the lead up to the nationwide release of RHDVa-K5 (GI.1aP-GI.1a) in 2017, an existing citizen science program, RabbitScan, was augmented to allow members of the public to submit samples collected from dead leporids for lagovirus testing. This study describes the information obtained from the increased number of leporid samples received between 2015 and 2022 and focuses on the recent epidemiological interactions and evolutionary trajectory of circulating lagoviruses in Australia between October 2020 and December 2022. A total of 2771 samples were tested from January 2015 to December 2022, of which 1643 were lagovirus-positive. Notable changes in the distribution of lagovirus variants were observed, predominantly in Western Australia, where RHDV2-4c (GI.4cP-GI.2) was detected again in 2021 after initially being reported to be present in 2018. Interestingly, we found evidence that the deliberately released RHDVa-K5 was able to establish and circulate in wild rabbit populations in WA. Overall, the incorporation of citizen science approaches proved to be a cost-efficient method to increase the sampling area and enable an in-depth analysis of lagovirus distribution, genetic diversity, and interactions. The maintenance of such programs is essential to enable continued investigations of the critical parameters affecting the biocontrol of feral rabbit populations in Australia, as well as to enable the detection of any potential future incursions.

Immunological Cross-Protection between Different Rabbit Hemorrhagic Disease Viruses-Implications for Rabbit Biocontrol and Vaccine Development.

The use of rabbit hemorrhagic disease virus (RHDV) as a biocontrol agent to control feral rabbit populations in Australia, in combination with circulating endemic strains, provides a unique environment to observe the interactions between different lagoviruses competing for the same host. Following the arrival of RHDV2 (GI.2) in Australia, it became necessary to investigate the potential for immunological cross-protection between different variants, and the implications of this for biocontrol programs and vaccine development. Laboratory rabbits of various immune status-(1) rabbits with no detectable immunity against RHDV; (2) rabbits with experimentally acquired immunity after laboratory challenge; (3) rabbits immunised with a GI.2-specific or a multivalent RHDV inactivated virus prototype vaccine; or (4) rabbits with naturally acquired immunity-were challenged with one of three different RHDV variants (GI.1c, GI.1a or GI.2). The degree of cross-protection observed in immune rabbits was associated with the variant used for challenge, infectious dose of the virus and age, or time since acquisition of the immunity, at challenge. The immune status of feral rabbit populations should be determined prior to intentional RHDV release because of the high survival proportions in rabbits with pre-existing immunity. In addition, to protect domestic rabbits in Australia, a multivalent RHDV vaccine should be considered because of the limited cross-protection observed in rabbits given monovalent vaccines.

Traumatic brain injury in precariously housed persons: Incidence and risks.

BACKGROUND: Homeless and precarious housed persons are particularly prone to traumatic brain injuries (TBIs), but existent incidence rates are hampered by poor case acquisition. We rigorously documented TBIs in precariously housed persons transitioning in and out of homelessness. METHODS: Between December 2016 and May 2018, 326 precariously housed participants enrolled in a longitudinal study in Vancouver, Canada were assessed monthly for TBI occurrences after education on sequelae. Over one participant-year, 2433 TBI screenings were acquired for 326 person-years and variables associated with odds of incident TBI were evaluated. FINDINGS: One hundred participants acquired 175 TBIs, yielding an observed incidence proportion of 30·7% and event proportion of 53·7%. Of the injured, 61% reported one TBI and 39% reported multiple injuries. Acute intoxication was present for more than half of the TBI events assessed. Additionally, 9·7% of TBI events occurred in the context of a drug overdose. Common injury mechanisms were falls (45·1%), assaults (25·1%), and hitting one's head on an object (13·1%). In this community-based but non-randomly recruited sample, exploratory analyses identified factors associated with odds of an incident TBI over one year of follow-up, including: schizophrenia disorders (odds ratio (OR) = 0·43, 95% confidence interval (CI) 0·19, 0·94), role functioning (OR = 0·69, 95% CI 0·52, 0·91), opioid dependence (OR = 2·17, 95% CI 1·27, 3·72) and those reporting past TBIs (OR = 1·99, 95% CI 1·13, 3·52). INTERPRETATION: Given the ubiquity of TBIs revealed in this precariously housed sample, we identify an underappreciated and urgent healthcare priority. Several factors modified the odds of incident TBI, which can facilitate investigations into targeted prevention efforts. FUNDING: Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, William and Ada Isabelle Steel Research Fund, Simon Fraser University Vice-President Research Undergraduate Student Research Award and Simon Fraser University Psychology Department Research Grant.

Passive Immunisation against RHDV2 Induces Protection against Disease but Not Infection.

Rabbit haemorrhagic disease virus 2 (RHDV2) is a lagovirus in the family Caliciviridae. The closely related Rabbit haemorrhagic disease virus (RHDV, termed RHDV1 throughout this manuscript for clarity) has been used extensively as a biocontrol agent in Australia since the mid-1990s to manage wild rabbit populations, a major economic and environmental pest species. Releasing RHDV1 into populations with a high proportion of rabbits less than 8-10 weeks of age leads to non-lethal infection in many of these young animals, with subsequent seroconversion and long-term immunity against reinfection. In contrast, RHDV2 causes lethal disease even in young rabbits, potentially offering substantial benefits for rabbit management programs over RHDV1. However, it is not clear how acquired resistance from maternal antibodies may influence immunity after RHDV2 infection. In this study, we assessed serological responses after RHDV2 challenge in young rabbits of three different ages (5-, 7-, or 9-weeks-old) that were passively immunised with either high- (titre of 2560 by RHDV IgG ELISA; 2.41 mg/mL total protein) or low- (titre of 160-640 by RHDV IgG ELISA; 1.41 mg/mL total protein) dose RHDV2 IgG to simulate maternal antibodies. All rabbits treated with a high dose and 75% of those treated with a low dose of RHDV2 IgG survived virus challenge. Surviving animals developed robust lagovirus-specific IgA, IgM, and IgG responses within 10 days post infection. These findings demonstrate that the protection against RHDV2 conferred by passive immunisation is not sterilising. Correspondingly, this suggests that the presence of maternal antibodies in wild rabbit populations may impede the effectiveness of RHDV2 as a biocontrol.

Age and Infectious Dose Significantly Affect Disease Progression after RHDV2 Infection in Naïve Domestic Rabbits.

Rabbit haemorrhagic disease virus 2 (RHDV2 or GI.2, referring to any virus with lagovirus GI.2 structural genes) is a recently emerged calicivirus that causes generalised hepatic necrosis and disseminated intravascular coagulation leading to death in susceptible lagomorphs (rabbits and hares). Previous studies investigating the virulence of RHDV2 have reported conflicting results, with case fatality rates ranging from 0% to 100% even within a single study. Lagoviruses are of particular importance in Australia and New Zealand where they are used as biocontrol agents to manage wild rabbit populations, which threaten over 300 native species and result in economic impacts in excess of $200 million AUD annually to Australian agricultural industries. It is critically important that any pest control method is both highly effective (i.e., virulent, in the context of viral biocontrols) and has minimal animal welfare impacts. To determine whether RHDV2 might be a suitable candidate biocontrol agent, we investigated the virulence and disease progression of a naturally occurring Australian recombinant RHDV2 in both 5-week-old and 11-week-old New Zealand White laboratory rabbits after either high or low dose oral infection. Objective measures of disease progression were recorded through continuous body temperature monitoring collars, continuous activity monitors, and twice daily observations. We observed a 100% case fatality rate in both infected kittens and adult rabbits after either high dose or low dose infection. Clinical signs of disease, such as pyrexia, weight loss, and reduced activity, were evident in the late stages of infection. Clinical disease, i.e., welfare impacts, were limited to the period after the onset of pyrexia, lasting on average 12 h and increasing in severity as disease progressed. These findings confirm the high virulence of this RHDV2 variant in naïve rabbits. While age and infectious dose significantly affected disease progression, the case fatality rate was consistently 100% under all conditions tested.

Prolonged Detection of Bovine Viral Diarrhoea Virus Infection in the Semen of Bulls.

Infection of bulls with bovine viral diarrhoea virus (BVDV) can result in the development of virus persistence, confined to the reproductive tract. These bulls develop a normal immune response with high neutralizing antibody titres. However, BVDV can be excreted in the semen for a prolonged period. Although relatively rare, in this study we describe six separate cases in bulls being prepared for admission to artificial breeding centres. Semen samples were tested in a pan-Pestivirus-reactive real-time PCR assay and viral RNA was detected in semen from five of the bulls for three to eight months after infection. In one bull, virus was detected at low levels for more than five years. This bull was found to have one small testis. When slaughtered, virus was only detected in the abnormal testis. The low levels of BVDV in the semen of these bulls were only intermittently detected by virus isolation in cell culture. This virus-contaminated semen presents a biosecurity risk and confirms the need to screen all batches of semen from bulls that have been previously infected with BVDV. The use of real-time PCR is recommended as the preferred laboratory assay for this purpose.

Cognitive Impairment in Marginally Housed Youth: Prevalence and Risk Factors.

Objective: Homeless and marginally housed youth are particularly vulnerable members of society, and are known to experience numerous health problems, including psychiatric illness, substance use, and viral infection. Despite the presence of these risk factors for cognitive compromise, there is limited research on the cognitive functioning of homeless and marginally housed youth. The present study examines the degree and pattern of cognitive impairment and associations with key risk factors in a sample of marginally housed young adults. Method: Participants (N = 101) aged 20-29 years old were recruited from single-room occupancy hotels, and underwent cognitive, psychiatric, neurological, and serological assessments. Results: Forty percent of participants were identified as mildly cognitively impaired across multiple domains, and 16% were moderately-severely impaired. Deficits in memory and attention were most prevalent, while impairments in inhibitory control/processing speed and cognitive flexibility were also present but tended to be less severe. Developmental and historical factors (premorbid intellectual functioning, neurological soft signs, earlier exposure to and longer duration of homelessness or marginal housing), as well as current health risks (stimulant dependence and hepatitis C exposure), were associated with cognitive impairment. Conclusions: The strikingly high rate of cognitive impairment in marginally housed young adults represents a major public health concern and is likely to pose a significant barrier to treatment and rehabilitation. These results suggest that the pathway to cognitive impairment involves both developmental vulnerability and modifiable risk factors. This study highlights the need for early interventions that address cognitive impairment and risk factors in marginalized young people.

Traumatic Brain Injury in a Community-Based Cohort of Homeless and Vulnerably Housed Individuals.

We characterized traumatic brain injury (TBI) and studied its associations with mental and physical health in a community cohort of homeless and vulnerably housed individuals. Detailed mental and physical health structured interviews, neuropsychological testing, and multimodal magnetic resonance imaging (MRI) were performed on 283 participants. Two TBI participant groups were defined for primary analyses: those with a self-reported history of TBI and those with MRI confirmation of TBI. By self-report, 174 participants (61.5%) reported a previous serious head or face injury (symptomatic or asymptomatic), with 100 (35.3%) experiencing symptoms consistent with TBI (any post-injury loss of consciousness, confusion, or memory loss). Persons self-reporting TBI had poorer current mental and physical health, more ongoing neurological symptoms, and a higher rate of mood disorders, compared to those with no TBI. The presence of a mood disorder, a TBI history, and an interaction between these factors contributed to lower mental health. There was evidence of TBI in 20 participants (6.9%) on clinical MRI sequences. These participants had globally lower cortical gray matter volumes and lower white matter fractional anisotropy (FA) values. Neurocognitive test scores positively correlated with both FA and cortical gray matter volumes in participants with MRI evidence of trauma. Previous TBI is associated with poorer mental and physical health in homeless and vulnerably housed individuals and interacts with mood disorders to exacerbate poor mental health. Focal traumatic lesions evident on MRI are associated with diffusely lower gray matter volumes and white matter integrity, which predict cognitive functioning.