Developing transmissible vaccines for animal infections.

Intrinsically safe designs and a staged transparent development process will be essential.

Effect of inlet-outlet configurations on the cross-transmission of airborne bacteria between animal production buildings.

Cross-transmission of airborne pathogens between buildings facilitates the spread of both human and animal diseases. Rational spatial arrangement of buildings and air inlet-outlet design are well-established preventive measures, but the effectiveness of current configurations for mitigating pathogens cross-transmission is still under assessment. An intensive field study in a laying hen farm was conducted to elucidate the spatial distribution of airborne bacteria (AB) and the source of AB at the inlets under different wind regimes. We found higher concentrations of AB at the interspace and sidewall inlets of buildings with sidewall exhaust systems than at those with endwall exhaust systems. We observed significant differences in bacterial diversity and richness at the interspace and sidewall inlets between buildings with side exhaust systems and those with endwall exhaust systems. We further found that the AB emitted from buildings could translocate to the sidewall inlets of adjacent building to a greater extent between buildings with sidewall exhaust systems than between those with endwall exhaust systems. Our findings revealed that sidewall exhaust systems aggravate cross-transmission of AB between buildings, suggesting that endwall exhaust systems or other compensatory preventive measures combined with sidewall exhaust systems could be a better choice to suppress airborne cross-transmission.

Quantifying the effectiveness of betaherpesvirus-vectored transmissible vaccines.

Transmissible vaccines have the potential to revolutionize how zoonotic pathogens are controlled within wildlife reservoirs. A key challenge that must be overcome is identifying viral vectors that can rapidly spread immunity through a reservoir population. Because they are broadly distributed taxonomically, species specific, and stable to genetic manipulation, betaherpesviruses are leading candidates for use as transmissible vaccine vectors. Here we evaluate the likely effectiveness of betaherpesvirus-vectored transmissible vaccines by developing and parameterizing a mathematical model using data from captive and free-living mouse populations infected with murine cytomegalovirus (MCMV). Simulations of our parameterized model demonstrate rapid and effective control for a range of pathogens, with pathogen elimination frequently occurring within a year of vaccine introduction. Our results also suggest, however, that the effectiveness of transmissible vaccines may vary across reservoir populations and with respect to the specific vector strain used to construct the vaccine.

Natural rodent model of viral transmission reveals biological features of virus population dynamics.

Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis.

Infection evolution and spreading models in non-uniform biological systems.

The paper investigates peculiarities of infection evolution and spreading models in non-uniform biological systems of individuals (humans, animals, plants) using the approach of mathematical modeling. The effects of different characteristic features are revealed. A robust tool for prediction of infection evolution (growth and spreading) under different external conditions is developed accounting for spatial non-uniformity of governing parameters.

Infection and transmission of ancestral SARS-CoV-2 and its alpha variant in pregnant white-tailed deer.

ABSTRACTSARS-CoV-2 was first reported circulating in human populations in December 2019 and has since become a global pandemic. Recent history involving SARS-like coronavirus outbreaks have demonstrated the significant role of intermediate hosts in viral maintenance and transmission. Evidence of SARS-CoV-2 natural infection and experimental infections of a wide variety of animal species has been demonstrated, and in silico and in vitro studies have indicated that deer are susceptible to SARS-CoV-2 infection. White-tailed deer (WTD) are amongst the most abundant and geographically widespread wild ruminant species in the US. Recently, WTD fawns were shown to be susceptible to SARS-CoV-2. In the present study, we investigated the susceptibility and transmission of SARS-CoV-2 in adult WTD. In addition, we examined the competition of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the alpha variant of concern (VOC) B.1.1.7 through co-infection of WTD. Next-generation sequencing was used to determine the presence and transmission of each strain in the co-infected and contact sentinel animals. Our results demonstrate that adult WTD are highly susceptible to SARS-CoV-2 infection and can transmit the virus through direct contact as well as vertically from doe to fetus. Additionally, we determined that the alpha VOC B.1.1.7 isolate of SARS-CoV-2 outcompetes the ancestral lineage A isolate in WTD, as demonstrated by the genome of the virus shed from nasal and oral cavities from principal infected and contact animals, and from the genome of virus present in tissues of principal infected deer, fetuses and contact animals.

Adaptation, spread and transmission of SARS-CoV-2 in farmed minks and associated humans in the Netherlands.

In the first wave of the COVID-19 pandemic (April 2020), SARS-CoV-2 was detected in farmed minks and genomic sequencing was performed on mink farms and farm personnel. Here, we describe the outbreak and use sequence data with Bayesian phylodynamic methods to explore SARS-CoV-2 transmission in minks and humans on farms. High number of farm infections (68/126) in minks and farm workers (>50% of farms) were detected, with limited community spread. Three of five initial introductions of SARS-CoV-2 led to subsequent spread between mink farms until November 2020. Viruses belonging to the largest cluster acquired an amino acid substitution in the receptor binding domain of the Spike protein (position 486), evolved faster and spread longer and more widely. Movement of people and distance between farms were statistically significant predictors of virus dispersal between farms. Our study provides novel insights into SARS-CoV-2 transmission between mink farms and highlights the importance of combining genetic information with epidemiological information when investigating outbreaks at the animal-human interface.

Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses.

To date, no evidence supports the fact that animals play a role in the epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus infectious disease 2019 (COVID-19). However, several animal species are naturally susceptible to SARS-CoV-2 infection. Besides pets (cats, dogs, Syrian hamsters, and ferrets) and farm animals (minks), different zoo animal species have tested positive for SARS-CoV-2 (large felids and non-human primates). After the summer of 2020, a second wave of SARS-CoV-2 infection occurred in Barcelona (Spain), reaching a peak of positive cases in November. During that period, four lions (Panthera leo) at the Barcelona Zoo and three caretakers developed respiratory signs and tested positive for the SARS-CoV-2 antigen. Lion infection was monitored for several weeks and nasal, fecal, saliva, and blood samples were taken at different time-points. SARS-CoV-2 RNA was detected in nasal samples from all studied lions and the viral RNA was detected up to two weeks after the initial viral positive test in three out of four animals. The SARS-CoV-2 genome was also detected in the feces of animals at different times. Virus isolation was successful only from respiratory samples of two lions at an early time-point. The four animals developed neutralizing antibodies after the infection that were detectable four months after the initial diagnosis. The partial SARS-CoV-2 genome sequence from one animal caretaker was identical to the sequences obtained from lions. Chronology of the events, the viral dynamics, and the genomic data support human-to-lion transmission as the origin of infection.

'It's our job': Constraints to investigation of atypical disease events-Opinions of Australian veterinarians.

Frontline health practitioners need to be adequately prepared to recognize and respond to atypical disease presentations, some of which may have zoonotic potential. Data from previous research have suggested that veterinarians may face challenges in investigation of disease events due to time and money constraints. As part of an Australia-wide survey project, veterinarians were asked to answer an open-ended question regarding potential constraints in investigation of atypical disease events where there may be concern about a zoonosis or emerging infectious disease. Qualitative data were analysed using thematic content analysis with the consideration of the respondent's area of practice and level of experience. Five main themes were identified which encapsulated constraints to disease investigation described by participants, namely: (a) financing of disease investigations, including client willingness/ability to pay in absence of alternative government schemes; (b) client-related factors, including willingness to consent to investigation and comply with instructions; (c) professional preparedness to act, related to practitioner knowledge and technical competency; (d) workplace environment, impacted by physical, logistical and managerial aspects of workplaces; and (e) access to external technical support, primarily from government veterinary services. Successful investigation and management of atypical diseases, including potential zoonoses, requires preparedness of all veterinarians. Continuing professional education for veterinarians in infection prevention and control and biosecurity, alongside adequate government funding and support will help facilitate optimal health and biosecurity outcomes. Both state and federal governments need to review existing animal health structures to ensure cohesive responses for future disease events.

Elephant Endotheliotropic Herpesvirus Is Omnipresent in Elephants in European Zoos and an Asian Elephant Range Country.

Elephant endotheliotropic herpesviruses (EEHVs) may cause acute, often lethal, hemorrhagic disease (EEHV-HD) in young elephants. Prevalence of EEHV in different elephant populations is still largely unknown. In order to improve diagnostic tools for the detection of EEHV infections and to obtain insight into its spread among elephants, we developed novel ELISAs based on EEHV1A gB and gH/gL. Performance of the ELISAs was assessed using sera from 41 European zoo elephants and 69 semi-captive elephants from Laos, one of the Asian elephant range countries. Sera from all (sub)adult animals tested (≥5 years of age) showed high reactivity with both gB and gH/gL, indicating that EEHV prevalence has been highly underestimated so far. Reactivity towards the antigens was generally lower for sera of juvenile animals (1 > 5 years). Only one (juvenile) animal, which was sampled directly after succumbing to EEHV-HD, was found to be seronegative for EEHV. The two other EEHV-HD cases tested showed low antibody levels, suggesting that all three cases died upon a primary EEHV infection. In conclusion, our study suggests that essentially all (semi-)captive (sub)adult elephants in European zoos and in Laos carry EEHV, and that young elephants with low antibody levels are at risk of dying from EEHV-HD.

Brucellosis in wildlife in Africa: a systematic review and meta-analysis.

This study aimed to consolidate current knowledge of wildlife brucellosis in Africa and to analyse available predictors of infection. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Information on species, test used, test results, area, rainfall, livestock and wildlife contact and year of study were extracted. This systematic review revealed 42 prevalence studies, nine disease control articles and six articles on epidemiology. Brucella abortus, Brucella melitensis, Brucella inopinata and Brucella suis were reported in wildlife. The prevalence studies revealed serological evidence of brucellosis in buffalo, antelope (positive in 14/28 species), carnivores (4/12) and other species (7/20) over the last five decades. Buffalo populations were more likely to be infected and had a higher seroprevalence than other species; the pooled seroprevalence was 13.7% (95% CI 10.3-17.3%) in buffalo, 7.1% (95% CI 1.1-15.5%) in carnivores and 2.1% (95% CI 0.1-4.9%) in antelope. Wildlife in high rainfall areas (≥ 800 mm) were more likely to be infected, and infected populations showed higher seroprevalence in high rainfall areas and in studies published after 2000. Domestic animal contact was associated with increased seroprevalence in antelope and carnivore species, but not in buffalo, supporting the hypothesis that buffalo may be a reservoir species.

SARS-CoV-2 infection in farmed minks, associated zoonotic concerns, and importance of the One Health approach during the ongoing COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has now affected over 72.5 million people worldwide, with nearly 1.6 million deaths reported globally as of December 17, 2020. SARS-CoV-2 has been implicated to have originated from bats and pangolins, and its intermediate animal hosts are being investigated. Crossing of the species barrier and exhibition of zoonosis have been reported in SARS-CoV-2 in farm (minks), domesticated (cats and dogs), and wild animals (tigers, puma, and lions). Recently, the rapid spread of SARS-CoV-2 infection was reported in mink farms, which led to the death of a myriad minks. The clinical and pathological findings of SARS-CoV-2 infection and the rapid animal-to-animal transmission in minks are almost similar to the findings observed in patients with COVID-19. Additionally, the rapid virus transmission among minks and the associated mutations resulted in a new mink-associated variant that was identified in both minks and humans, thereby providing evidence of mink-to-human transmission of SARS-CoV-2. The new mink-associated SARS-CoV-2 variant with a possible reduced sensitivity to neutralizing antibodies poses serious risks and is expected to have a direct effect on the diagnostic techniques, therapeutics, and vaccines that are currently under development. This article highlights the current evidence of SARS-CoV-2 infection in farmed minks, and provides an understanding of the pathogenesis of COVID-19 in minks and the associated zoonotic concerns of SARS-CoV-2 transmission from minks to humans with an emphasis on appropriate mitigation measures and on the necessity of adopting the One Health approach during the COVID-19 pandemic.

Challenges in Having Vaccines Available to Control Transboundary Diseases of Livestock.

The global human population is growing at a rapid rate leading to the need for continued expansion of food animal production to meet the world's increasing nutritional requirements. As a consequence of this increased production demand, the use of high volume, animal dense systems have expanded providing high quality protein at reduced costs. Backyard animal production has also expanded. This increased food animal production has facilitated the rapid spread, mutation, and adaptation of pathogens to new hosts. This scenario continues to drive the emergence and reemergence of diseases in livestock species increasing the urgency for development and availability of vaccines for transboundary animal diseases (TADs). Even though vaccines are widely recognized as being an essential tool for control of TADs, there are many scientific, economic, political, and logistical challenges to having vaccine available to control an outbreak. This article will focus on examples of the challenges associated with having vaccines available for emergency response, as well as the characteristics of 'ideal' TAD vaccines, the need for complementary diagnostic assays, and hurdles involved in bringing efficacious veterinary TAD vaccines to market including regulatory constraints and considerations for stockpiling vaccines for emergency use in non-endemic countries. Examples will also highlight the complicated interplay between animal health and human health and demonstrate the lasting benefits that can be gained from an efficacious vaccine.

Avian Influenza A Virus Associations in Wild, Terrestrial Mammals: A Review of Potential Synanthropic Vectors to Poultry Facilities.

The potential role of wild mammals in the epidemiology of influenza A viruses (IAVs) at the farm-side level has gained increasing consideration over the past two decades. In some instances, select mammals may be more likely to visit riparian areas (both close and distant to farms) as well as poultry farms, as compared to traditional reservoir hosts, such as waterfowl. Of significance, many mammalian species can successfully replicate and shed multiple avian IAVs to high titers without prior virus adaptation and often can shed virus in greater quantities than synanthropic avian species. Within this review, we summarize and discuss the potential risks that synanthropic mammals could pose by trafficking IAVs to poultry operations based on current and historic literature.

Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils.

Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018. DFT1 diverged early into five clades, three spreading widely and two failing to persist. One clade has replaced others at several sites, and rates of DFT1 coinfection are high. DFT1 gradually accumulates copy number variants (CNVs), and its telomere lengths are short but constant. Recurrent CNVs reveal genes under positive selection, sites of genome instability, and repeated loss of a small derived chromosome. Cultured DFT1 cell lines have increased CNV frequency and undergo highly reproducible convergent evolution. Overall, DFT1 is a remarkably stable lineage whose genome illustrates how cancer cells adapt to diverse environments and persist in a parasitic niche.

Varroa destructor mites vector and transmit pathogenic honey bee viruses acquired from an artificial diet.

The ectoparasitic mite Varroa destructor is one of the most destructive pests of the honey bee (Apis mellifera) and the primary biotic cause of colony collapse in many regions of the world. These mites inflict physical injury on their honey bee hosts from feeding on host hemolymph and fat body cells/cellular components, and serve as the vector for deadly honey bee viruses, including Deformed wing virus (DWV) and the related Varroa destructor virus-1 (VDV-1) (i.e., DWV-like viruses). Studies focused on elucidating the dynamics of Varroa-mediated vectoring and transmission of DWV-like viruses may be confounded by viruses present in ingested host tissues or the mites themselves. Here we describe a system that includes an artificial diet free of insect tissue-derived components for maintaining Varroa mites for in vitro experimentation. Using this system, together with the novel engineered cDNA clone-derived genetically tagged VDV-1 and wild-type DWV, we demonstrated for the first time that Varroa mites provided an artificial diet supplemented with engineered viruses for 36 hours could acquire and transmit sufficient numbers of virus particles to establish an infection in virus-naïve hosts. While the in vitro system described herein provides for only up to five days of mite survival, precluding study of the long-term impacts of viruses on mite health, the system allows for extensive insights into the dynamics of Varroa-mediated vectoring and transmission of honey bee viruses.

Towards integrated surveillance-response systems for the prevention of future pandemics.

Most human pathogens originate from non-human hosts and certain pathogens persist in animal reservoirs. The transmission of such pathogens to humans may lead to self-sustaining chains of transmission. These pathogens represent the highest risk for future pandemics. For their prevention, the transmission over the species barrier - although rare - should, by all means, be avoided. In the current COVID-19 pandemic, surprisingly though, most of the current research concentrates on the control by drugs and vaccines, while comparatively little scientific inquiry focuses on future prevention. Already in 2012, the World Bank recommended to engage in a systemic One Health approach for zoonoses control, considering integrated surveillance-response and control of human and animal diseases for primarily economic reasons. First examples, like integrated West Nile virus surveillance in mosquitos, wild birds, horses and humans in Italy show evidence of financial savings from a closer cooperation of human and animal health sectors. Provided a zoonotic origin can be ascertained for the COVID-19 pandemic, integrated wildlife, domestic animal and humans disease surveillance-response may contribute to prevent future outbreaks. In conclusion, the earlier a zoonotic pathogen can be detected in the environment, in wildlife or in domestic animals; and the better human, animal and environmental surveillance communicate with each other to prevent an outbreak, the lower are the cumulative costs.

A unifying framework for the transient parasite dynamics of migratory hosts.

Migrations allow animals to track seasonal changes in resources, find mates, and avoid harsh climates, but these regular, long-distance movements also have implications for parasite dynamics and animal health. Migratory animals have been dubbed "superspreaders" of infection, but migration can also reduce parasite burdens within host populations via migratory escape from contaminated habitats and transmission hotspots, migratory recovery due to parasite mortality, and migratory culling of infected individuals. Here, we show that a single migratory host-macroparasite model can give rise to these different phenomena under different parametrizations, providing a unifying framework for a mechanistic understanding of the parasite dynamics of migratory animals. Importantly, our model includes the impact of parasite burden on host movement capability during migration, which can lead to "parasite-induced migratory stalling" due to a positive feedback between increasing parasite burdens and reduced movement. Our results provide general insight into the conditions leading to different health outcomes in migratory wildlife. Our approach lays the foundation for tactical models that can help understand, predict, and mitigate future changes of disease risk in migratory wildlife that may arise from shifting migratory patterns, loss of migratory behavior, or climate effects on parasite development, mortality, and transmission.