Modeling zoonotic and vector-borne viruses.

The 2013-2016 Ebola virus disease epidemic and the coronavirus disease 2019 pandemic galvanized tremendous growth in models for emerging zoonotic and vector-borne viruses. Therefore, we have reviewed the main goals and methods of models to guide scientists and decision-makers. The elements of models for emerging viruses vary across spectrums: from understanding the past to forecasting the future, using data across space and time, and using statistical versus mechanistic methods. Hybrid/ensemble models and artificial intelligence offer new opportunities for modeling. Despite this progress, challenges remain in translating models into actionable decisions, particularly in areas at highest risk for viral disease outbreaks. To address this issue, we must identify gaps in models for specific viruses, strengthen validation, and involve policymakers in model development.

Evaluating the epizootic and zoonotic threat of an H7N9 low-pathogenicity avian influenza virus (LPAIV) variant associated with enhanced pathogenicity in turkeys.

Between 2013 and 2017, the A/Anhui/1/13-lineage (H7N9) low-pathogenicity avian influenza virus (LPAIV) was epizootic in chickens in China, causing mild disease, with 616 fatal human cases. Despite poultry vaccination, H7N9 has not been eradicated. Previously, we demonstrated increased pathogenesis in turkeys infected with H7N9, correlating with the emergence of the L217Q (L226Q H3 numbering) polymorphism in the haemagglutinin (HA) protein. A Q217-containing virus also arose and is now dominant in China following vaccination. We compared infection and transmission of this Q217-containing 'turkey-adapted' (ty-ad) isolate alongside the H7N9 (L217) wild-type (wt) virus in different poultry species and investigated the zoonotic potential in the ferret model. Both wt and ty-ad viruses demonstrated similar shedding and transmission in turkeys and chickens. However, the ty-ad virus was significantly more pathogenic than the wt virus in turkeys but not in chickens, causing 100 and 33% mortality in turkeys respectively. Expanded tissue tropism was seen for the ty-ad virus in turkeys but not in chickens, yet the viral cell receptor distribution was broadly similar in the visceral organs of both species. The ty-ad virus required exogenous trypsin for in vitro replication yet had increased replication in primary avian cells. Replication was comparable in mammalian cells, and the ty-ad virus replicated successfully in ferrets. The L217Q polymorphism also affected antigenicity. Therefore, H7N9 infection in turkeys can generate novel variants with increased risk through altered pathogenicity and potential HA antigenic escape. These findings emphasize the requirement for enhanced surveillance and understanding of A/Anhui/1/13-lineage viruses and their risk to different species.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

Epidemiological modeling of SARS-CoV-2 in white-tailed deer (Odocoileus virginianus) reveals conditions for introduction and widespread transmission.

Emerging infectious diseases with zoonotic potential often have complex socioecological dynamics and limited ecological data, requiring integration of epidemiological modeling with surveillance. Although our understanding of SARS-CoV-2 has advanced considerably since its detection in late 2019, the factors influencing its introduction and transmission in wildlife hosts, particularly white-tailed deer (Odocoileus virginianus), remain poorly understood. We use a Susceptible-Infected-Recovered-Susceptible epidemiological model to investigate the spillover risk and transmission dynamics of SARS-CoV-2 in wild and captive white-tailed deer populations across various simulated scenarios. We found that captive scenarios pose a higher risk of SARS-CoV-2 introduction from humans into deer herds and subsequent transmission among deer, compared to wild herds. However, even in wild herds, the transmission risk is often substantial enough to sustain infections. Furthermore, we demonstrate that the strength of introduction from humans influences outbreak characteristics only to a certain extent. Transmission among deer was frequently sufficient for widespread outbreaks in deer populations, regardless of the initial level of introduction. We also explore the potential for fence line interactions between captive and wild deer to elevate outbreak metrics in wild herds that have the lowest risk of introduction and sustained transmission. Our results indicate that SARS-CoV-2 could be introduced and maintained in deer herds across a range of circumstances based on testing a range of introduction and transmission risks in various captive and wild scenarios. Our approach and findings will aid One Health strategies that mitigate persistent SARS-CoV-2 outbreaks in white-tailed deer populations and potential spillback to humans.

Exploring the Potential of Muridae as Sentinels for Human and Zoonotic Viruses.

In recent years, the transmission of viruses from wildlife to humans has raised significant public health concerns, exemplified by the COVID-19 pandemic caused by the betacoronavirus SARS-CoV-2. Human activities play a substantial role in increasing the risk of zoonotic virus transmission from wildlife to humans. Rats and mice are prevalent in urban environments and may act as reservoirs for various pathogens. This study aimed to evaluate the presence of zoonotic viruses in wild rats and mice in both urban and rural areas, focusing on well-known zoonotic viruses such as betacoronavirus, hantavirus, arenavirus, kobuvirus, and monkeypox virus, along with other viruses occasionally detected in rats and mice, including rotavirus, norovirus, and astrovirus, which are known to infect humans at a high rate. A total of 128 animals were captured, including 70 brown rats (Rattus norvegicus), 45 black rats (Rattus rattus), and 13 house mice (Mus musculus), and feces, lung, and liver were collected. Among brown rats, one fecal sample tested positive for astrovirus RNA. Nucleotide sequencing revealed high sequence similarity to both human and rat astrovirus, suggesting co-presence of these viruses in the feces. Murine kobuvirus (MuKV) was detected in fecal samples from both black (n = 7) and brown (n = 6) rats, primarily from urban areas, as confirmed by sequence analysis. These findings highlight the importance of surveillance and research to understand and mitigate the risks associated with the potential transmission of pathogens by rodents.

Exploring Potential Intermediates in the Cross-Species Transmission of Influenza A Virus to Humans.

The influenza A virus (IAV) has been a major cause of several pandemics, underscoring the importance of elucidating its transmission dynamics. This review investigates potential intermediate hosts in the cross-species transmission of IAV to humans, focusing on the factors that facilitate zoonotic events. We evaluate the roles of various animal hosts, including pigs, galliformes, companion animals, minks, marine mammals, and other animals, in the spread of IAV to humans.

Hantavirus Expansion Trends in Natural Host Populations in Brazil.

Hantaviruses are zoonotic agents responsible for causing Hantavirus Cardiopulmonary Syndrome (HCPS) in the Americas, with Brazil ranking first in number of confirmed HCPS cases in South America. In this study, we simulate the monthly spread of highly lethal hantavirus in natural hosts by conjugating a Kermack-McCormick SIR model with a cellular automata model (CA), therefore simultaneously evaluating both in-cell and between-cell infection dynamics in host populations, using recently compiled data on main host species abundances and confirmed deaths by hantavirus infection. For both host species, our models predict an increase in the area of infection, with 22 municipalities where no cases have been confirmed to date expected to have at least one case in the next decade, and a reduction in infection in 11 municipalities. Our findings support existing research and reveal new areas where hantavirus is likely to spread within recognized epicenters. Highlighting spatial-temporal trends and potential expansion, we emphasize the increased risk due to pervasive habitat fragmentation and agricultural expansion. Consistent prevention efforts and One Health actions are crucial, especially in newly identified high-risk municipalities.

The Transmission of SARS-CoV-2 from COVID-19-Diagnosed People to Their Pet Dogs and Cats in a Multi-Year Surveillance Project.

Recent emerging zoonotic disease outbreaks, such as that of SARS-CoV-2, have demonstrated the need for wider companion animal disease surveillance. We tested 1000 dogs and cats belonging to employees of a US veterinary hospital network that were exposed to human COVID-19 cases in the household between 1 January 2020 and 10 March 2022 for SARS-CoV-2 and surveyed their owners about clinical signs and risk factors. The seropositivity was 33% for 747 dogs and 27% for 253 cats. Pet seropositivity correlated with the US human case rates over time, exhibiting peaks corresponding with the major COVID-19 surges. Antibodies persisted longer than previously documented (828 days in dogs; 650 days in cats). Increasing age and duration of proximity to infected people were associated with increased seropositivity in dogs but not cats. Cats were more likely to have clinical signs, but an association between seropositivity and the presence of clinical signs was not found in either species.

Rabies virus circulation in a highly diverse bat assemblage from a high-risk area for zoonoses outbreaks in the Brazilian Amazon.

Bats are the second most diverse order of mammals and play a central role in ecosystem dynamics. They are also important reservoirs of potentially zoonotic microorganisms, of which rabies virus is the most lethal among the bat-transmitted zoonotic pathogens. Importantly, recent outbreaks of human rabies have been reported from the Brazilian Amazon. Here we present a survey of bat species and rabies virus (RABV) circulation in a bat assemblage in the Marajó region, northern Brazil. Using data from mist-net captures and bioacoustic sampling, 56 bat species were recorded along the Jacundá River basin over a 10-day expedition in November 2022. For the investigation of RABV, we used the direct fluorescent antibody test (DFAT) and the rapid fluorescent focus inhibition test (RFFIT). In total, 159 bat individuals from 22 species were investigated for RABV. Five adults of the common vampire bat, Desmodus rotundus, showed RABV-specific antibodies in serum samples. Additionally, we report on local residents with injuries caused by D. rotundus bites and the occurrence of colonies of non-hematophagous bats from different species roosting inside human residences. This scenario raises concerns about the risks of new cases of human rabies and other zoonotic diseases associated with bats in the region and highlights the need for epidemiological surveillance and mitigation measures to prevent outbreaks of emerging infectious diseases.

Zoonotic spillover and viral mutations from low and middle-income countries: improving prevention strategies and bridging policy gaps.

The increasing frequency of zoonotic spillover events and viral mutations in low and middle-income countries presents a critical global health challenge. Contributing factors encompass cultural practices like bushmeat consumption, wildlife trade for traditional medicine, habitat disruption, and the encroachment of impoverished settlements onto natural habitats. The existing "vaccine gap" in many developing countries exacerbates the situation by allowing unchecked viral replication and the emergence of novel mutant viruses. Despite global health policies addressing the root causes of zoonotic disease emergence, there is a significant absence of concrete prevention-oriented initiatives, posing a potential risk to vulnerable populations. This article is targeted at policymakers, public health professionals, researchers, and global health stakeholders, particularly those engaged in zoonotic disease prevention and control in low and middle-income countries. The article underscores the importance of assessing potential zoonotic diseases at the animal-human interface and comprehending historical factors contributing to spillover events. To bridge policy gaps, comprehensive strategies are proposed that include education, collaborations, specialized task forces, environmental sampling, and the establishment of integrated diagnostic laboratories. These strategies advocate simplicity and unity, breaking down barriers, and placing humanity at the forefront of addressing global health challenges. Such a strategic and mental shift is crucial for constructing a more resilient and equitable world in the face of emerging zoonotic threats.

Breaking the Barrier: SARS-CoV-2 Infections in Wild and Companion Animals and Their Implications for Public Health.

The emergence of the novel coronavirus SARS-CoV-2 has led to significant interest in its potential transmission between animals and humans, especially pets. This review article summarises the literature on coronavirus infections in domestic animals, emphasising epidemiology, transmission dynamics, clinical manifestations, and public health implications. This article highlights current understandings of the relationship between infections in companion animals and humans, identifies research gaps, and suggests directions for future research. Cases of disease in cats, dogs, and other domestic animals, often occurring through close contact with infected owners, are reviewed, raising concerns about possible zoonotic and reverse zoonotic transmission. Precautions and recommendations for pet owners and healthcare workers are also discussed. The scientific evidence presented in the article highlights the need for a One Health approach that considers the health of people, animals, and the environment to combat future pandemics.

Zoonotic spillover and extreme weather events drive the global outbreaks of airborne viral emerging infectious diseases.

Outbreaks of airborne viral emerging infectious diseases (EIDs) cause an increasing burden on global public health, particularly with a backdrop of intensified climate change. However, infection sources and drivers for outbreaks of airborne viral EIDs remain unknown. Here, we aim to explore the driving mechanisms of outbreaks based on the one health perspective. Outbreak information for 20 types of airborne viral EIDs was collected from the Global Infectious Disease and Epidemiology Network database and a systematic literature review. Four statistically significant and high-risk spatiotemporal clusters for airborne viral EID outbreaks were identified globally using multivariate scan statistic tests. There were 112 outbreaks with clear infection sources, and zoonotic spillover was the most common source (95.54%, 107/112). Since 1970, the majority of outbreaks occurred in healthcare facilities (24.82%), followed by schools (17.93%) and animal-related settings (15.93%). Significant associations were detected between the number of earthquakes, storms, duration of floods, and airborne viral EIDs' outbreaks using a case-crossover study design and multivariable conditional logistic regression. These findings implied that zoonotic spillover and extreme weather events are driving global outbreaks of airborne viral EIDs, and targeted prevention and control measures should be made to reduce the airborne viral EIDs burden.

Astroviruses in terrestrial Malagasy mammals.

Small terrestrial mammals are major hosts of infectious agents responsible for zoonotic diseases. Astroviruses (AstVs)-the cause of non-bacterial gastroenteritis mainly affecting young children-have been detected in a wide array of mammalian and avian host species. However, understanding the factors that influence AstV infection within and across hosts is limited. Here, we investigated the impact of land use changes on AstVs in terrestrial small mammals in rural northeastern Madagascar. We sampled 515 small mammals, representing seven endemic and four introduced species. Twenty-two positive samples were identified, all but one of which were found in the introduced species Mus musculus and Rattus rattus (family Muridae), with a positivity rate of 7.7% (6/78) and 5.6% (15/266), respectively. The non-introduced rodent case was from an endemic shrew-tenrec (family Tenrecidae). We found the highest positivity rate of AstVs infection in brushy regrowth (17.5%, 7/40) as compared to flooded rice fields (4.60%, 8/174), secondary forest (4.1%, 3/74), agroforest (3.6%, 1/28), village (2.61%, 3/115), and semi-intact forest (0%, 0/84). A phylogenetic analysis revealed an association between AstVs and their rodent host species. None of the viruses were phylogenetically related to AstVs previously described in Malagasy bats. This study supports AstV circulation in synanthropic animals in agricultural habitats of Madagascar and highlights the need to assess the spillover risk to human populations in rural areas.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

Monkeypox: Past, Present, and Future.

Monkeypox (Mpox) is a zoonotic disease caused by a virus (monkeypox virus-MPV) belonging to the Poxviridae family. In humans, the disease has an incubation period of 5-21 days and then progresses in two phases, the prodromal phase and the rash phase. The prodromal phase is characterized by non-specific symptoms such as fever, muscle pain, malaise, lymphadenopathy, headache, and chills. Skin lesions appear in the rash phase of the disease. These lesions progress through different stages (macules, papules, vesicles, and pustules). In May 2022, WHO reported an outbreak of human Mpox in several countries which were previously Mpox-free. As per the CDC report of March 01, 2023, a total of 86,231 confirmed cases of Mpox and 105 deaths have been reported from 110 countries and territories across the globe. Notably, more than 90% of these countries were reporting Mpox for the first time. The phylogenetic analysis revealed that this outbreak was associated with the virus from the West African clade. However, most of the cases in this outbreak had no evidence of travel histories to MPV-endemic countries in Central or West Africa. This outbreak was primarily driven by the transmission of the virus via intimate contact in men who have sex with men (MSM). The changing epidemiology of Mpox raised concerns about the increasing spread of the disease in non-endemic countries and the urgent need to control and prevent it. In this chapter, we present all the documented cases of Mpox from 1970 to 2023 and discuss the past, present, and future of MPV.

Poxviruses from the Concept of One Health.

In the last 4 years, the world has experienced two pandemics of bat-borne viruses. Firstly, in 2019 the SARS-CoV-2 pandemic started and has been causing millions of deaths around the world. In 2022, a Monkeypox pandemic rose in various countries of the world. Those pandemics have witnessed movements and initiatives from healthcare and research institutions to establish a worldwide understanding to battle any future pandemics and biological threats. One Health concept is a modern, comprehensive, unifying ways to improve humans, animals, and ecosystems' health. This concept shows how much they are intertwined and related to one another, whether it is an environmental, or a pathological relation. This review aims to describe Poxviridae and its impact on the One Health concept, by studying the underlying causes of how poxviruses can affect the health of animals, humans, and environments. Reviewing the effect of disease transmission between animal to human, human to human, and animal to animal with pox viruses as a third party to achieve a total understanding of infection and viral transmission. Thus, contributing to enhance detection, diagnosis, research, and treatments regarding the application of One Health.

Zoonotic and Zooanthroponotic Potential of Monkeypox.

The current multicounty outbreak of monkeypox virus (MPXV) posed an emerging and continued challenge to already strained public healthcare sector, around the globe. Since its first identification, monkeypox disease (mpox) remained enzootic in Central and West African countries where reports of human cases are sporadically described. Recent trends in mpox spread outside the Africa have highlighted increased incidence of spillover of the MPXV from animal to humans. While nature of established animal reservoirs remained undefined, several small mammals including rodents, carnivores, lagomorphs, insectivores, non-human primates, domestic/farm animals, and several species of wildlife are proposed to be carrier of the MPXV infection. There are established records of animal-to-human (zoonotic) spread of MPXV through close interaction of humans with animals by eating bushmeat, contracting bodily fluids or trading possibly infected animals. In contrast, there are reports and increasing possibilities of human-to-animal (zooanthroponotic) spread of the MPXV through petting and close interaction with pet owners and animal care workers. We describe here the rationales and molecular factors which predispose the spread of MPXV not only amongst humans but also from animals to humans. A range of continuing opportunities for the spread and evolution of MPXV are discussed to consider risks beyond the currently identified groups. With the possibility of MPXV establishing itself in animal reservoirs, continued and broad surveillance, investigation into unconventional transmissions, and exploration of spillover events are warranted.

Orf, a Human Parapoxvirus Infection.

Despite being common worldwide, parapoxvirus infections are regarded as neglected zoonoses because their incidence is either unknown or grossly overestimated. In ruminants all throughout the world, parapoxvirus produces oral lesions and infectious pustular dermatitis. The pathogen is typically spread directly via items contaminated with parapoxvirus and indirectly via a near contact with dermatological lesions that contain the virus on affected animals. Animals infected with the parapoxvirus typically exhibit no clinical symptoms, and the mode of parapoxvirus transmission is occasionally unclear. For accurate etiological diagnosis and appropriate therapy of patients affected by zoonotic infections, the significance of adopting a "One Health" approach and cross-sector collaboration between human and veterinary medicine should be emphasized. The causative pathogen of ecthyma contagiosum in general people is the orf virus, which mostly infects various animals, either pets or wildlife species. The illness primarily affects minute wild ruminants, sheep, cattle, deer, and goats, and it can spread to people through contact with infected animals or contaminated meats anywhere in the world. Taxonomically speaking, the virus belongs to the parapoxvirus genus. Thus pathogen can be detected from crusts for a very long period (several months to several years), and the virus is found to be resistant to inactivation with a hot or dry atmosphere. In immunocompetent individuals, the lesions often go away on their own with a period as long 2 months. Nevertheless, it necessitates the applying of diverse strategies, such as antiviral, immunological modulator, or modest surgical excisions in immunosuppressed patients. The interaction of the virus with various host populations aids in the development of a defense mechanism against the immune system. The parapoxvirus illness in humans is covered in this chapter. The orf illness, a significant known human parapoxvirus infection, is given specific attention.

Monkeypox Outbreak 2022, from a Rare Disease to Global Health Emergence: Implications for Travellers.

Monkeypox (mpox), a zoonotic disease caused by the monkeypox virus (MPXV), poses a significant public health threat with the potential for global dissemination beyond its endemic regions in Central and West Africa. This study explores the multifaceted aspects of monkeypox, covering its epidemiology, genomics, travel-related spread, mass gathering implications, and economic consequences. Epidemiologically, mpox exhibits distinct patterns, with variations in age and gender susceptibility. Severe cases can arise in immunocompromised individuals, underscoring the importance of understanding the factors contributing to its transmission. Genomic analysis of MPXV highlights its evolutionary relationship with the variola virus and vaccinia virus. Different MPXV clades exhibit varying levels of virulence and transmission potential, with Clade I associated with higher mortality rates. Moreover, the role of recombination in MPXV evolution remains a subject of interest, with implications for understanding its genetic diversity. Travel and mass gatherings play a pivotal role in the spread of monkeypox. The ease of international travel and increasing globalization have led to outbreaks beyond African borders. The economic ramifications of mpox outbreaks extend beyond public health. Direct treatment costs, productivity losses, and resource-intensive control efforts can strain healthcare systems and economies. While vaccination and mitigation strategies have proven effective, the cost-effectiveness of routine vaccination in non-endemic countries remains a subject of debate. This study emphasizes the role of travel, mass gatherings, and genomics in its spread and underscores the economic impacts on affected regions. Enhancing surveillance, vaccination strategies, and public health measures are essential in controlling this emerging infectious disease.