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Common carp (Cyprinus carpio) are a serious invasive species of riverine habitats in Australia and several control measures have been proposed. The strategy and potential success of any control measure will be influenced by carp population dynamics. Carp survival and distribution are driven by abiotic environmental factors (e.g., water flow rates and habitat availability), which vary greatly in space and time in Australian river systems. To inform realistic control strategies, we developed a mechanistic (process-based) carp metapopulation model with parameters explicitly linked to spatio-temporal estimates of habitat suitability. To demonstrate the use of this model, we evaluated how recovery times following a one-time management action (that results in population reduction) varied across five river catchments in the Murray-Darling Basin (MDB), eastern Australia, using reconstructed environmental conditions from the early 1990s to 2016. We found that recovery time at the catchment scale can be highly dependent on the flood-drought cycle, with recovery varying from to 2 to 10 years between wet and dry periods. In more stable catchments, however, ~ 6 years (range 4–8 years) is more likely. Our results are consistent with the paradigm that carp are a highly successful invasive species, with strong recovery potential, especially during periods of access to quality nursery habitat (i.e., during floodplain and wetland inundation). [ABSTRACT FROM AUTHOR]

Modeling the windborne transmission of aerosolized pathogens is challenging. We adapted an atmospheric dispersion model (ADM) to simulate the windborne dispersion of porcine reproductive and respiratory syndrome virus (PRRSv) between swine farms. This work focuses on determining ADM applicable parameter values for PRRSv through a literature and expert opinion-based approach. The parameters included epidemiological features of PRRSv, characteristics of the aerosolized particles, and survival of aerosolized virus in relation to key meteorological features. A case study was undertaken to perform a sensitivity analysis on key parameters. Farms experiencing ongoing PRRSv outbreaks were assigned as particle emitting sources. The wind data from the North American Mesoscale Forecast System was used to simulate dispersion. The risk was estimated semi-quantitatively based on the median daily deposition of particles and the distance to the closest emitting farm. Among the parameters tested, the ADM was most sensitive to the number of particles emitted, followed by the model runtime, and the release height was the least sensitive. Farms within 25 km from an emitting farm were at the highest risk; with 53.66% being within 10 km. An ADM-based risk estimation of windborne transmission of PRRSv may inform optimum time intervals for air sampling, plan preventive measures, and aid in ruling out the windborne dispersion in outbreak investigations. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the infectious disease COVID-19, which has rapidly become an international pandemic with significant impact on healthcare systems and the global economy. To assist antiviral therapy and vaccine development efforts, we performed a natural history/time course study of SARS-CoV-2 infection in ferrets to characterise and assess the suitability of this animal model. Ten ferrets of each sex were challenged intranasally with 4.64 × 104 TCID50 of SARS-CoV-2 isolate Australia/VIC01/2020 and monitored for clinical disease signs, viral shedding, and tissues collected post-mortem for histopathological and virological assessment at set intervals. We found that SARS-CoV-2 replicated in the upper respiratory tract of ferrets with consistent viral shedding in nasal wash samples and oral swab samples up until day 9. Infectious SARS-CoV-2 was recovered from nasal washes, oral swabs, nasal turbinates, pharynx, and olfactory bulb samples within 3–7 days post-challenge; however, only viral RNA was detected by qRT-PCR in samples collected from the trachea, lung, and parts of the gastrointestinal tract. Viral antigen was seen exclusively in nasal epithelium and associated sloughed cells and draining lymph nodes upon immunohistochemical staining. Due to the absence of clinical signs after viral challenge, our ferret model is appropriate for studying asymptomatic SARS-CoV-2 infections and most suitable for use in vaccine efficacy studies. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is an emerging virus that has caused significant human morbidity and mortality since its detection in late 2019. With the rapid emergence has come an unprecedented programme of vaccine development with at least 300 candidates under development. Ferrets have proven to be an appropriate animal model for testing safety and efficacy of SARS‐CoV‐2 vaccines due to quantifiable virus shedding in nasal washes and oral swabs. Here, we outline our efforts early in the SARS‐CoV‐2 outbreak to propagate and characterize an Australian isolate of the virus in vitro and in an ex vivo model of human airway epithelium, as well as to demonstrate the susceptibility of domestic ferrets (Mustela putorius furo) to SARS‐CoV‐2 infection following intranasal challenge. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic has resulted in significant global morbidity and mortality on a scale similar to the influenza pandemic of 1918. Over the course of the last few months, a number of SARS-CoV-2 variants have been identified against which vaccine-induced immune responses may be less effective. These "variants-of-concern" have garnered significant attention in the media, with discussion around their impact on the future of the pandemic and the ability of leading COVID-19 vaccines to protect against them effectively. To address concerns about emerging SARS-CoV-2 variants affecting vaccine-induced immunity, we investigated the neutralisation of representative 'G614', '501Y.V1' and '501Y.V2' virus isolates using sera from ferrets that had received prime-boost doses of the DNA vaccine, INO-4800. Neutralisation titres against G614 and 501Y.V1 were comparable, but titres against the 501Y.V2 variant were approximately 4-fold lower, similar to results reported with other nucleic acid vaccines and supported by in silico biomolecular modelling. The results confirm that the vaccine-induced neutralising antibodies generated by INO-4800 remain effective against current variants-of-concern, albeit with lower neutralisation titres against 501Y.V2 similar to other leading nucleic acid-based vaccines. [ABSTRACT FROM AUTHOR]

Vaccines against SARS-CoV-2 are likely to be critical in the management of the ongoing pandemic. A number of candidates are in Phase III human clinical trials, including ChAdOx1 nCoV-19 (AZD1222), a replication-deficient chimpanzee adenovirus-vectored vaccine candidate. In preclinical trials, the efficacy of ChAdOx1 nCoV-19 against SARS-CoV-2 challenge was evaluated in a ferret model of infection. Groups of ferrets received either prime-only or prime-boost administration of ChAdOx1 nCoV-19 via the intramuscular or intranasal route. All ChAdOx1 nCoV-19 administration combinations resulted in significant reductions in viral loads in nasal-wash and oral swab samples. No vaccine-associated adverse events were observed associated with the ChAdOx1 nCoV-19 candidate, with the data from this study suggesting it could be an effective and safe vaccine against COVID-19. Our study also indicates the potential for intranasal administration as a way to further improve the efficacy of this leading vaccine candidate. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is an acute, highly contagious viral disease of domestic and wild cloven-hoofed animals, caused by FMD virus (FMDV). An FMD outbreak can cause major production losses and have significant implications for trade. Vaccination can assist in controlling the disease, and emergency vaccination using high antigen payload vaccines (>6 PD50/dose) is considered an important control approach in the event of an outbreak. In recent years there has been a divergence of serotype A viruses in South East Asia (SEA) into several distinct genetic and antigenic clusters. Numerous variants were found to poorly match serotype A vaccines commonly included in international antigen banks. This study examined the ability of single vaccination with high-potency monovalent A22 IRQ vaccine to protect sheep following challenge with the A/VIT/15/2012 strain, just four days following vaccination. The vaccine proved effective at limiting clinical disease but did not prevent infection. [ABSTRACT FROM AUTHOR]

Although vaccination of poultry for control of highly pathogenic avian influenza virus (HPAIV) H5N1 has been practiced during the last decade in several countries, its effectiveness under field conditions remains largely unquantified. Effective HPAI vaccination is however essential in preventing incursions, silent infections and generation of new H5N1 antigenic variants. The objective of this study was to asses the level and duration of vaccine induced immunity in commercial layers in Indonesia. Titres of H5N1 haemagglutination inhibition (HI) antibodies were followed in individual birds from sixteen flocks, age 18–68 week old (wo). The study revealed that H5N1 vaccination had highly variable outcome, including vaccination failures, and was largely ineffective in providing long lasting protective immunity. Flocks were vaccinated with seven different vaccines, administer at various times that could be grouped into three regimes: In regime A, flocks (n = 8) were vaccinated two or three times before 19 wo; in regime B (n = 2), two times before and once after 19 wo; and in regime C (n = 6) three to four times before and two to three times after 19 wo. HI titres in regime C birds were significantly higher during the entire observation period in comparison to titres of regime A or B birds, which also differed significantly from each other. The HI titres of individual birds in each flock differed significantly from birds in other flocks, indicating that the effectiveness of field vaccination was highly variable and farm related. Protective HI titres of >4log2, were present in the majority of flocks at 18 wo, declined thereafter at variable rate and only two regime C flocks had protective HI titres at 68 wo. Laboratory challenge with HPAIV H5N1 of birds from regime A and C flocks confirmed that protective immunity differed significantly between flocks vaccinated by these two regimes. The study revealed that effectiveness of the currently applied H5N1 vaccination could be improved and measures to achieve this are discussed. [ABSTRACT FROM AUTHOR]

Invasive wildlife often causes serious damage to the economy and agriculture as well as environmental, human and animal health. Habitat models can fill knowledge gaps about species distributions and assist planning to mitigate impacts. Yet, model accuracy and utility may be compromised by small study areas and limited integration of species ecology or temporal variability. Here we modelled seasonal habitat suitability for wild pigs, a widespread and harmful invader, in northern Australia. We developed a resource-based, spatially-explicit and regional-scale approach using Bayesian networks and spatial pattern suitability analysis. We integrated important ecological factors such as variability in environmental conditions, breeding requirements and home range movements. The habitat model was parameterized during a structured, iterative expert elicitation process and applied to a wet season and a dry season scenario. Model performance and uncertainty was evaluated against independent distributional data sets. Validation results showed that an expert-averaged model accurately predicted empirical wild pig presences in northern Australia for both seasonal scenarios. Model uncertainty was largely associated with different expert assumptions about wild pigs’ resource-seeking home range movements. Habitat suitability varied considerably between seasons, retracting to resource-abundant rainforest, wetland and agricultural refuge areas during the dry season and expanding widely into surrounding grassland floodplains, savanna woodlands and coastal shrubs during the wet season. Overall, our model suggested that suitable wild pig habitat is less widely available in northern Australia than previously thought. Mapped results may be used to quantify impacts, assess risks, justify management investments and target control activities. Our methods are applicable to other wide-ranging species, especially in data-poor situations. [ABSTRACT FROM AUTHOR]

We studied the clinical and epidemiologic features of an outbreak of Crimean-Congo hemorrhagic fever in Herat Province, Afghanistan. The study comprised 63 patients hospitalized in 2017. The overall case-fatality rate was 22.2%; fatal outcome was significantly associated with a negative IgM test result, longer prothrombin time, and nausea. [ABSTRACT FROM AUTHOR]

A peptide enzyme linked immunosorbent assay (ELISA) based on an epitope in the haemagglutinin (HA) of avian influenza virus H5N1, amino acid positions 274-288 (HA274-288) was evaluated for detection of H5N1-specific antibodies. An optimized ELISA based on the tetrameric form of the HA274-288 epitope designated MP15 gave low background with non- immune chicken sera and detected vaccinated and infected birds. The HA274-288 epitope was highly conserved in Indonesian H5N1 strains and antibody responses were detected in the majority of the vaccinated chickens regardless of the H5N1 strain used for vaccination. The HA274-288 epitope was also conserved in the majority of H5N1 strains from the neighbouring Asian region, and other H5 subtypes potentially allowing for a wider use of the MP15 ELISA in H5N1 vaccinated and infected flocks. The MP15 ELISA results correlated significantly with haemagglutination inhibition (HI) test results and test sensitivity and specificity were 87% and 92%, respectively. The MP15 ELISA titres were significantly higher than the HI titres in all immune sera allowing for sera to be tested at a single dilution of 1:400 which is of advantage in routine surveillance. The study indicated that the MP15 ELISA is potentially useful for serological detection of H5N1 vaccinated or infected poultry and to have some advantages over the standard HI test for routine monitoring of flocks' immunity after vaccination. [ABSTRACT FROM AUTHOR]

We conducted a challenge/rechallenge trial in which 3 alpacas were infected with Middle East respiratory syndrome coronavirus. The alpacas shed virus at challenge but were refractory to further shedding at rechallenge on day 21. The trial indicates that alpacas may be suitable models for infection and shedding dynamics of this virus. [ABSTRACT FROM AUTHOR]

In Lao People’s Democratic Republic pigs are kept in close contact with families. Human risk of infection with pig zoonoses arises from direct contact and consumption of unsafe pig products. This cross-sectional study was conducted in Luang Prabang (north) and Savannakhet (central-south) Provinces. A total of 59 villages, 895 humans and 647 pigs were sampled and serologically tested for zoonotic pathogens including: hepatitis E virus (HEV), Japanese encephalitis virus (JEV) and Trichinella spiralis; In addition, human sera were tested for Taenia spp. and cysticercosis. Seroprevalence of zoonotic pathogens in humans was high for HEV (Luang Prabang: 48.6%, Savannakhet: 77.7%) and T. spiralis (Luang Prabang: 59.0%, Savannakhet: 40.5%), and lower for JEV (around 5%), Taenia spp. (around 3%) and cysticercosis (Luang Prabang: 6.1, Savannakhet 1.5%). Multiple correspondence analysis and hierarchical clustering of principal components was performed on descriptive data of human hygiene practices, contact with pigs and consumption of pork products. Three clusters were identified: Cluster 1 had low pig contact and good hygiene practices, but had higher risk of T. spiralis. Most people in cluster 2 were involved in pig slaughter (83.7%), handled raw meat or offal (99.4%) and consumed raw pigs’ blood (76.4%). Compared to cluster 1, cluster 2 had increased odds of testing seropositive for HEV and JEV. Cluster 3 had the lowest sanitation access and had the highest risk of HEV, cysticercosis and Taenia spp. Farmers which kept their pigs tethered (as opposed to penned) and disposed of manure in water sources had 0.85 (95% CI: 0.18 to 0.91) and 2.39 (95% CI: 1.07 to 5.34) times the odds of having pigs test seropositive for HEV, respectively. The results have been used to identify entry-points for intervention and management strategies to reduce disease exposure in humans and pigs, informing control activities in a cysticercosis hyper-endemic village. [ABSTRACT FROM AUTHOR]

Background: Recent increased activity of the mosquito-borne Murray Valley encephalitis virus (MVEV) in Australia has renewed concerns regarding its potential to spread and cause disease. Methodology/Principal Findings: To better understand the genetic relationships between earlier and more recent circulating strains, patterns of virus movement, as well as the molecular basis of MVEV evolution, complete pre-membrane (prM) and Envelope (Env) genes were sequenced from sixty-six MVEV strains from different regions of the Australasian region, isolated over a sixty year period (1951–2011). Phylogenetic analyses indicated that, of the four recognized genotypes, only G1 and G2 are contemporary. G1 viruses were dominant over the sampling period and found across the known geographic range of MVEV. Two distinct sub-lineages of G1 were observed (1A and 1B). Although G1B strains have been isolated from across mainland Australia, Australian G1A strains have not been detected outside northwest Australia. Similarly, G2 is comprised of only Western Australian isolates from mosquitoes, suggesting G1B and G2 viruses have geographic or ecological restrictions. No evidence of recombination was found and a single amino acid substitution in the Env protein (S332G) was found to be under positive selection, while several others were found to be under directional evolution. Evolutionary analyses indicated that extant genotypes of MVEV began to diverge from a common ancestor approximately 200 years ago. G2 was the first genotype to diverge, followed by G3 and G4, and finally G1, from which subtypes G1A and G1B diverged between 1964 and 1994. Conclusions/Significance: The results of this study provides new insights into the genetic diversity and evolution of MVEV. The demonstration of co-circulation of all contemporary genetic lineages of MVEV in northwestern Australia, supports the contention that this region is the enzootic focus for this virus. [ABSTRACT FROM AUTHOR]

The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio-economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host-pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

A surveillance method able to differentiate between vaccinated and infected poultry is required for those countries that practice vaccination against highly pathogenic avian influenza H5N1. The external domain of the M2 protein (M2e) of influenza virus is a potentially useful differentiating-infected from vaccinated animals (DIVA) antigen but little is known about the M2e antibody response and factors influencing its detection. In this study, the M2e antibody response was characterized in layer birds vaccinated and challenged with an Indonesian H5N1 virus isolate, using a single M2e peptide or four-branched multiple antigenic peptide form of M2e (MAP-M2e) as antigens in two separate ELISAs. Anti-M2e antibodies were absent in chicks with high level of maternal haemagglutination inhibition antibodies and also in all layers vaccinated once, twice or three times with an inactivated commercial H5N1 vaccine. In contrast, anti-M2e antibodies were detected in vaccinated layers challenged with H5N1 virus and their presence was associated with virus isolation and an increase in haemagglutination inhibition titres. The number of birds that developed M2e antibodies, as well as the strength and duration of the M2e antibody response were strongly influenced by the length of the interval between vaccination and challenge. Birds challenged at six weeks after vaccination all developed M2e antibodies by 14 days that lasted until at least 56 days after infection. In birds challenged at two weeks after vaccination, only a proportion of birds developed M2e antibodies by 14 days that lasted only until 28 days post-infection. Both single M2e peptide and MAP-M2e ELISAs had high diagnostic specificity but the diagnostic sensitivity of MAP-M2e ELISA was significantly higher and more effective in detecting M2e antibody in immune and infected birds. The results show that MAP-M2e ELISA would be useful for surveillance in countries using vaccination to control highly pathogenic avian influenza H5N1. [ABSTRACT FROM PUBLISHER]

Background Previous studies investigating long-distance, wind-borne dispersal of Culicoides have utilised outbreaks of clinical disease (passive surveillance) to assess the relationship between incursion and dispersal event. In this study, species of exotic Culicoides and isolates of novel bluetongue viruses, collected as part of an active arbovirus surveillance program, were used for the first time to assess dispersal into an endemic region. Results A plausible dispersal event was determined for five of the six cases examined. These include exotic Culicoides specimens for which a possible dispersal event was identified within the range of two days - three weeks prior to their collection and novel bluetongue viruses for which a dispersal event was identified between one week and two months prior to their detection in cattle. The source location varied, but ranged from Lombok, in eastern Indonesia, to Timor-Leste and southern Papua New Guinea. Conclusions Where bluetongue virus is endemic, the concurrent use of an atmospheric dispersal model alongside existing arbovirus and Culicoides surveillance may help guide the strategic use of limited surveillance resources as well as contribute to continued model validation and refinement. Further, the value of active surveillance systems in evaluating models for longdistance dispersal is highlighted, particularly in endemic regions where knowledge of background virus and vector status is beneficial. [ABSTRACT FROM AUTHOR]

The paper is motivated by a problem in veterinary epidemiology, in which spatially referenced breakdowns of bovine tuberculosis are classified according to their genotype and year of occurrence. We develop a nonparametric method for addressing spatial segregation in the resulting multivariate spatial point process, with associated Monte Carlo tests for the null hypothesis that different genotypes are randomly intermingled and no temporal changes in spatial segregation. Our spatial segregation estimates use a kernel regression method with bandwidth selected by a multivariate cross-validated likelihood criterion. [ABSTRACT FROM AUTHOR]

Hendra virus (HeV) is a high consequence zoonotic pathogen found in Australia. The HeV vaccine was developed for use in horses and provides a One Health solution to the prevention of human disease. By protecting horses from infection, the vaccine indirectly protects humans as well, as horses are the only known source of infection for humans. The sub-unit-based vaccine, containing recombinant HeV soluble G (sG) glycoprotein, was released by Pfizer Animal Health (now Zoetis) for use in Australia at the end of 2012. The purpose of this study was to collate post-vaccination serum neutralising antibody titres as a way of assessing how the vaccine has been performing in the field. Serum neutralization tests (SNTs) were performed on serum samples from vaccinated horses submitted to the laboratory by veterinarians. The SNT results have been analysed, together with age, dates of vaccinations, date of sampling and location. Results from 332 horses formed the data set. Provided horses received at least three vaccinations (consisting of two doses 3–6 weeks apart, and a third dose six months later), horses had high neutralising titres (median titre for three or more vaccinations was 2048), and none tested negative. [ABSTRACT FROM AUTHOR]

The common carp (Cyprinus carpio) is an invasive species in the rivers and waterways of southeastern Australia, and it has been implicated in the serious decline of many native fish species. Over the past 50 years, various control options have been explored, and to date, these have been ineffective or cost-prohibitive. Most recently, cyprinid herpesvirus 3 (CyHV-3) has been proposed as a biocontrol agent because of its high specificity and mortality rate. However, the virus is known to be only effective in a permissive water temperature range of approximately 16–28 °C. To define when this occurs, we undertook a hydrological reconstruction of five diverse river catchments (>130,000 km2) of southeastern Australia over three decades. This confirmed, in the studied areas, that while water temperatures are permissive from spring through to autumn, the time of year that this starts and ends is highly variable, interannually, and with strong latitudinal and altitudinal gradients between and within catchments. The results show that the virus should be effective with respect to water temperature throughout the water temperature range that carp occur in most of southeastern Australia. However, detailed water temperature estimation would still be required to determine the exact week of the start of release in any given catchment. Referring to observations in wild carp populations, we point out the limitation of developing a "release strategy" based solely on water temperature modelling and the need to incorporate fish biology and ecology into this planning. [ABSTRACT FROM AUTHOR]

The 'D614G' mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and countermeasures that target this glycoprotein, necessitating frequent vaccine matching. Virus neutralisation assays were performed using sera from ferrets which received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation but are otherwise comparable. Through this approach, supported by biomolecular modelling of this mutation and the commonly-associated P314L mutation in the RNA-dependent RNA polymerase, we have shown that there is no experimental evidence to support this speculation. We additionally demonstrate that the putative elastase cleavage site introduced by the D614G mutation is unlikely to be accessible to proteases. [ABSTRACT FROM AUTHOR]

The respiratory Influenza A Viruses (IAVs) and emerging zoonotic viruses such as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pose a significant threat to human health. To accelerate our understanding of the host–pathogen response to respiratory viruses, the use of more complex in vitro systems such as normal human bronchial epithelial (NHBE) cell culture models has gained prominence as an alternative to animal models. NHBE cells were differentiated under air-liquid interface (ALI) conditions to form an in vitro pseudostratified epithelium. The responses of well-differentiated (wd) NHBE cells were examined following infection with the 2009 pandemic Influenza A/H1N1pdm09 strain or following challenge with the dsRNA mimic, poly(I:C). At 30 h postinfection with H1N1pdm09, the integrity of the airway epithelium was severely impaired and apical junction complex damage was exhibited by the disassembly of zona occludens-1 (ZO-1) from the cell cytoskeleton. wdNHBE cells produced an innate immune response to IAV-infection with increased transcription of pro- and anti-inflammatory cytokines and chemokines and the antiviral viperin but reduced expression of the mucin-encoding MUC5B, which may impair mucociliary clearance. Poly(I:C) produced similar responses to IAV, with the exception of MUC5B expression which was more than 3-fold higher than for control cells. This study demonstrates that wdNHBE cells are an appropriate ex-vivo model system to investigate the pathogenesis of respiratory viruses. [ABSTRACT FROM AUTHOR]