Spillover Events Research Articles

Domestic pigs are susceptible to experimental infection with non-human primate-derived Reston virus without the need for adaptation

Domestic pigs are a critical component of the food supply and one of the most commonly raised production animals. Pork consumption has driven the intensification of pig production expanding into environments conducive to increased emergence and spread of infectious diseases, including the spillover of pathogens into human populations. One of these emerging viruses, Reston virus (RESTV), is an enigma among the Orthoebolavirus genus in that its lack of human pathogenicity is in stark contrast to the high virulence associated with most other ebolaviruses. RESTV is, however, associated with outbreaks of highly lethal hemorrhagic disease in non-human primates (NHP), as well as poorly understood clinical manifestations of mixed virulence and lethality in naturally and experimentally infected domestic pigs. Our results show it is possible for RESTV derived from an NHP to infect domestic pigs resulting in a spectrum of disease, from asymptomatic to severe respiratory distress. Further, we report on the first experimental transmission of RESTV between infected pigs and a co-housed, naïve animal, as well as the first report of the successful use of group oral fluids for the detection of RESTV RNA and virus-specific IgA antibodies.

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.

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.

Addressing zoonotic disease transmission from temple monkeys to humans in Nepal.

Evidence of infection with the zoonotic pathogens has been reported from temple monkeys in Nepal. In this paper, the possible spillover of zoonotic pathogens from monkeys to humans is discussed.

Lassa virus in novel hosts: insights into the epidemiology of lassa virus infections in southern Nigeria

ABSTRACT Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021–2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown – specifically relating to pathogen diversity, evolution, and transmission – the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.

Recently Emerged Novel Henipa-like Viruses: Shining a Spotlight on the Shrew.

Henipaviruses are zoonotic viruses, including some highly pathogenic and capable of serious disease and high fatality rates in both animals and humans. Hendra virus and Nipah virus are the most notable henipaviruses, resulting in significant outbreaks across South Asia, South-East Asia, and Australia. Pteropid fruit bats have been identified as key zoonotic reservoirs; however, the increased discovery of henipaviruses outside the geographic distribution of Pteropid fruit bats and the detection of novel henipa-like viruses in other species such as the shrew, rat, and opossum suggest that Pteropid bats are not the sole reservoir for henipaviruses. In this review, we provide an update on henipavirus spillover events and describe the recent detection of novel unclassified henipaviruses, with a strong focus on the shrew and its emerging role as a key host of henipaviruses.

Ethical issues in Nipah virus control and research: addressing a neglected disease

Nipah virus is a priority pathogen that is receiving increasing attention among scientists and in work on epidemic preparedness. Despite this trend, there has been almost no bioethical work examining...

Baloxavir marboxil use for critical human infection of avian influenza A H5N6 virus

Recent outbreaks of avian influenza and ongoing virus reassortment have drawn focus on spill-over infections. The increase in human infections with highly pathogenic avian influenza H5N6 virus and its high fatality rate posed a potential threat, necessitating the search for a more effective treatment. Longitudinal clinical data and specimens were collected from five H5N6 patients after admission. All patients received antiviral treatment of either sequential monotherapy of oseltamivir and baloxavir or the two drugs in combination. Severity of illness; viral load in sputum, urine, and blood; and cytokine levels in serum and sputum were serially analyzed. All patients developed acute respiratory distress syndrome (ARDS) and viral sepsis within 1week after disease onset. When delayed oseltamivir showed poor effects, baloxavir was administered and rapidly decreased viral load. In addition, levels of IL-18, M-CSF, IL-6, and HGF in sputum and Mig and IL-18 in serum that reflected ARDS and sepsis deterioration, respectively, were also reduced with baloxavir usage. However, three patients eventually died from exacerbation of underlying disease and secondary bacterial infection. Nonsurvivors had more severe extrapulmonary organ dysfunction and insufficient H5N6 virus-specific antibody response. For critical human cases of H5N6 infection, baloxavir demonstrated effects on viral load and pulmonary/extrapulmonary cytokines, even though treatment was delayed. Baloxavir could be regarded as a first-line treatment to limit continued viral propagation, with potential future application in avian influenza human infections and poultry workers exhibiting influenza-like illness. This work was funded by the National Natural Science Foundation of China (81761128014).

Reported human infections of H9N2 avian influenza virus in China in 2021.

The continued emergence of human infections of H9N2 avian influenza virus (AIV) poses a serious threat to public health. The prevalent Y280/G9 lineage of H9N2 AIV in Chinese poultry can directly bind to human receptors, increasing the risk of spillover infections to humans. Since 2013, the number of human cases of H9N2 avian influenza has been increasing continuously, and in 2021, China reported the highest number of human cases, at 25. In this study, we analyzed the age, geographic, temporal, and sex distributions of humans with H9N2 avian influenza in 2021 using data from the National Influenza Center (Beijing, China). We also conducted evolutionary, gene homology, and molecular characterization analyses of the H9N2 AIVs infecting humans. Our findings show that children under the age of 12 accounted for 80% of human cases in 2021, and females were more frequently affected than males. More cases occurred in winter than in summer, and most cases were concentrated in southern China. Human-infecting H9N2 viruses showed a high level of genetic homology and belonged to the prevalent G57 genotype. Several additional α2,6-SA-binding sites and sites of mammalian adaptation were also identified in the genomes of human-infecting H9N2 viruses. Therefore, continuous monitoring of H9N2 AIV and the implementation of further measures to control the H9N2 virus in poultry are essential to reduce the interspecies transmission of the virus.

A Spatially Resolved and Environmentally Informed Forecast Model of West Nile Virus in Coachella Valley, California.

West Nile virus (WNV) is the most significant arbovirus in the United States in terms of both morbidity and mortality. West Nile exists in a complex transmission cycle between avian hosts and the arthropod vector, Culex spp. mosquitoes. Human spillover events occur when humans are bitten by an infected mosquito and predicting these rates of infection and therefore the risk to humans may be associated with fluctuations in environmental conditions. In this study, we evaluate the hydrological and meteorological drivers associated with mosquito biology and viral development to determine if these associations can be used to forecast seasonal mosquito infection rates with WNV in the Coachella Valley of California. We developed and tested a spatially resolved ensemble forecast model of the WNV mosquito infection rate in the Coachella Valley using 17years of mosquito surveillance data and North American Land Data Assimilation System-2 environmental data. Our multi-model inference system indicated that the combination of a cooler and dryer winter, followed by a wetter and warmer spring, and a cooler than normal summer was most predictive of the prevalence of West Nile positive mosquitoes in the Coachella Valley. The ability to make accurate early season predictions of West Nile risk has the potential to allow local abatement districts and public health entities to implement early season interventions such as targeted adulticiding and public health messaging before human transmission occurs. Such early and targeted interventions could better mitigate the risk of WNV to humans.

Cat–wildlife interactions and zoonotic disease risk: a call for more and better community science data

AbstractDue to their close interaction with both wildlife and humans, free‐ranging domestic animals are well‐suited to act as conveyors of zoonotic pathogens. Yet, although cats Felis catus are major predators of bats and other groups of zoonotic concern (e.g., rodents and birds), mounting evidence suggests that their role in the emergence of zoonotic diseases may be unappreciated. Here, we use bat–cat information extracted from the popular iNaturalist platform as a case in point to illustrate the potential of community science and social media to expand our understanding of pet‐wildlife interactions. Although observations of cats preying on bats were more prevalent in Europe and North America, evidence of such interactions was documented across different geographic regions, revealing a relatively high incidence of bat predation by cats and providing evidence of cat–bat interactions previously unreported in the scientific literature. The lack of surveillance focused on cats and other pets as bridging hosts for zoonotic spillover events is concerning, considering the recognised risks they pose. Community science is a relatively untapped source of information for pet‐wildlife interactions of zoonotic relevance. It is crucial that we gain a better understanding of the interaction between free‐ranging pets and wildlife to better understand their potential contribution to past and future disease outbreaks. Failing to do so not only jeopardises human health but also puts pets at risk.

Highly Pathogenic Avian Influenza A(H5N1) Virus Clade 2.3.4.4b Infections in Wild Terrestrial Mammals, United States, 2022.

We describe the pathology of natural infection with highly pathogenic avian influenza A(H5N1) virus of Eurasian lineage Goose/Guangdong clade 2.3.4.4b in 67 wild terrestrial mammals throughout the United States during April 1‒July 21, 2022. Affected mammals include 50 red foxes (Vulpes vulpes), 6 striped skunks (Mephitis mephitis), 4 raccoons (Procyon lotor), 2 bobcats (Lynx rufus), 2 Virginia opossums (Didelphis virginiana), 1 coyote (Canis latrans), 1 fisher (Pekania pennanti), and 1 gray fox (Urocyon cinereoargenteus). Infected mammals showed primarily neurologic signs. Necrotizing meningoencephalitis, interstitial pneumonia, and myocardial necrosis were the most common lesions; however, species variations in lesion distribution were observed. Genotype analysis of sequences from 48 animals indicates that these cases represent spillover infections from wild birds.

Understanding if the reward is worth the influenza risk: The true cost of showing pigs

Influenza A virus transmission between pigs and humans has been reported periodically worldwide, and spillover events across the animal-human species barrier could lead to the next influenza pandemic. Swine exhibitions serve as a unique interface conducive to zoonotic disease transmission due to extensive commingling of pigs and humans for prolonged periods of time. The majority of zoonotic influenza A virus transmission in the United States has been linked to swine exhibitions, leading some to suggest additional controls for influenza A virus at the swine-human interface. Determining the value of the exhibition swine industry and gauging the financial impacts influenza A virus outbreaks could have on society, helps to inform adoption decisions of mitigation recommendations. This study estimates the total value of the exhibition swine industry in the United States and calculates the predicted costs of the most extreme mitigation strategy, cancelling swine exhibitions to reduce zoonotic influenza A virus transmission. Mixed methods, including a survey, were used to collect data and inform the study model. We estimated that the direct economic impact of the exhibition swine sector in 2018 was $1.2 billion. If pig shows were to be cancelled for one year, the estimated direct economic impact would be $357.1 million. A permanent, > 3-year ban on swine exhibitions would result in a $665 million economic impact, which is a 45% reduction from baseline. The direct economic impact of cancelling the swine show circuit could not be determined, as youth exhibitors may pursue alternative activities that cannot be precisely accounted for. However, the estimated loss to the swine industry justifies seeking enhanced mitigation to prevent disease transmission. Moreover, economic losses secondary to exhibition cancellations may explain hesitancy to participate in active influenza A virus surveillance efforts.

Metagenomic Sequencing of Lloviu Virus from Dead Schreiber's Bats in Bosnia and Herzegovina.

Bats are a natural host for a number of viruses, many of which are zoonotic and thus present a threat to human health. RNA viruses of the family Filoviridae, many of which cause disease in humans, have been associated with specific bat hosts. Lloviu virus is a Filovirus which has been connected to mass mortality events in Miniopterus schreibersii colonies in Spain and Hungary, and some studies have indicated its immense zoonotic potential. A die-off has been recorded among Miniopterus schreibersii in eastern Bosnia and Herzegovina for the first time, prompting the investigation to determine the causative agent. Bat carcasses were collected and subjected to pathological examination, after which the lung samples with notable histopathological changes, lung samples with no changes and guano were analyzed using metagenomic sequencing and RT-PCR. A partial Lloviu virus genome was sequenced from lung samples with histopathological changes and found to be closely related to Hungarian and Italian virus sequences. Further accumulation of mutations on the GP gene, coding the glycoprotein responsible for cell tropism and host preference, enhances the need for further characterization and monitoring of this virus to prevent spillover events and protect human health.

Disease associations between honeybees and bumblebees as a threat to wild pollinators

​Emerging infectious diseases (EIDs) pose a risk to human welfare, both directly and indirectly, by affecting managed livestock and wildlife that provide valuable resources and ecosystem services, such as the pollination of crops. Honeybees (Apis mellifera), the prevailing managed insect crop pollinator, suffer from a range of emerging and exotic high-impact pathogens, and population maintenance requires active management by beekeepers to control them. Wild pollinators such as bumblebees (Bombus spp.) are in global decline, one cause of which may be pathogen spillover from managed pollinators like honeybees or commercial colonies of bumblebees. Here we use a combination of infection experiments and landscape-scale field data to show that honeybee EIDs are indeed widespread infectious agents within the pollinator assemblage. The prevalence of deformed wing virus (DWV) and the exotic parasite Nosema ceranae in honeybees and bumblebees is linked; as honeybees have higher DWV prevalence, and sympatric bumblebees and honeybees are infected by the same DWV strains, Apis is the likely source of at least one major EID in wild pollinators. Lessons learned from vertebrates highlight the need for increased pathogen control in managed bee species to maintain wild pollinators, as declines in native pollinators may be caused by interspecies pathogen transmission originating from managed pollinators.Nature 506: 364–366 (19 February 2014)

Assessing risk of Bombali virus spillover to humans by mutagenesis analysis of viral glycoprotein

Ebolaviruses, such as the highly pathogenic Ebola virus (EBOV), belong to the family Filoviridae and have caused outbreaks of severe and fatal hemorrhagic fever over the past years. Bombali virus (BOMV) is a newly discovered ebolavirus from bats with unknown potential to infect humans. For most ebolaviruses, the interaction between viral glycoprotein (GP) and host receptor Niemann-Pick C1 (NPC1) is crucial for viral entry and determines host tropism. Here, we analyzed the BOMV GP-mediated virus entry into human cells using our recently developed EBOV transcription- and replication-competent virus-like particle (trVLP) system. We demonstrated that while BOMV GP can be efficiently incorporated into trVLPs, it is inefficient in mediating trVLP entry into human cells. However, BOMV GP-mediated virus entry into human cells can be significantly enhanced by a few mutations in the NPC1-binding domain of GP. Furthermore, we showed that these mutations increase the binding of BOMV-GP to human NPC1. In summary, our results suggested that although wild-type BOMV does not efficiently infect human cells, the emergence of mutations in viral GP may boost its ability to spill over to humans, highlighting the importance of monitoring BOMV GP evolution in preventing potential BOMV spillover events.

A spatial analysis of urban gulls contribution to the potential spread of zoonotic and antibiotic-resistant bacteria

Wildlife human interactions within cities are becoming more common with consequences for pathogen transmission and human health. Large gulls are opportunistic feeders, adapted to coexist with humans in urban environments, and are potential vectors for spread and transmission of pathogens, including antimicrobial-resistant bacteria. We investigated the potential role that urban gulls play in the spread and dispersal of these bacteria. We analysed 129 faecal swabs from yellow-legged gulls (Larus michahellis) of different ages (56 adults and 73 immatures) during the breeding period from three years in the highly populated city of Barcelona (northeastern Spain). Thirteen individuals tested positive for the pathogenic bacteria (Escherichia coli, Listeria monocytogenes, Campylobacter jejuni), including antibiotic-resistant strains. We modelled the potential spatial spread of pathogens using the GPS trajectories of 58 yellow-legged gulls (23 adults, 35 immature individuals), which included the thirteen individuals that tested positive for pathogenic bacteria. By overlapping the spatially explicit pathogen dispersal maps with the distribution of urban installations sensitive at risk of possible pathogen spillover (e.g. elder and medical centres, markets, food industries, kindergartens, or public water sources), we identified potential areas at risk of pathogen spillover. Pathogens may be potentially spread to municipalities beyond Barcelona city borders. The results revealed that immature gulls dispersed pathogens over larger areas than adults (maximum dispersal distances of 167 km versus 53.2 km, respectively). Recreational urban water sources were the most sensitive habitats visited by GPS-tagged gulls that tested positive, followed by schools. Combining GPS movement data with pathogen analytics allows spatially explicit maps to be generated using a One Health approach that can help urban and public health management within large cities, such as Barcelona, and identify areas used by humans that are sensitive to pathogen spillover from gulls.

Antimicrobial resistance threatening animal-human health in Papua New Guinea

ABSTRACT Antimicrobial resistance (AMR) has the potential to reverse gains made in modern medicine and seriously jeopardize the lives of people and animals from infections that were once readily treatable (FAO/OIE 2015). Adopting a one health approach is critical to better understand and mitigate factors driving the emerging concern of AMR. Although the development and transmission of AMR in wildlife is not well understood, there is growing evidence that it is associated with proximity to humans or domestic animals. Papua New Guinea (PNG) faces some unique challenges for zoonotic spillover disease events and transmission of AMR between animals and humans. These challenges arise from the erosion of wildlife habitats due to deforestation and close contact of wildlife with villagers and their village-based livestock raised under free-range systems. Papua New Guinea’s human health system and the animal health field and laboratory services are resource-limited and are facing many human and animal disease challenges. The Fleming Fund Country Grant, implemented by the Burnet Institute Australia, is working with Papua New Guinea government and industry stakeholders to tackle AMR by encouraging information sharing, raising awareness, and supporting laboratory capacity in human and animal health for effective AMR surveillance. In addition, national legislation is being strengthened to support implementation of the Papua New Guinea Antimicrobial Resistance National Action Plan (Government of Papua New Guinea 2019) to encourage the judicious use and effective monitoring of antimicrobial medicines in humans and animals.

A mathematical model of Marburg virus disease outbreaks and the potential role of vaccination in control

BackgroundMarburg virus disease is an acute haemorrhagic fever caused by Marburg virus. Marburg virus is zoonotic, maintained in nature in Egyptian fruit bats, with occasional spillover infections into humans and nonhuman primates. Although rare, sporadic cases and outbreaks occur in Africa, usually associated with exposure to bats in mines or caves, and sometimes with secondary human-to-human transmission. Outbreaks outside of Africa have also occurred due to importation of infected monkeys. Although all previous Marburg virus disease outbreaks have been brought under control without vaccination, there is nevertheless the potential for large outbreaks when implementation of public health measures is not possible or breaks down. Vaccines could thus be an important additional tool, and development of several candidate vaccines is under way.MethodsWe developed a branching process model of Marburg virus transmission and investigated the potential effects of several prophylactic and reactive vaccination strategies in settings driven primarily by multiple spillover events as well as human-to-human transmission. Linelist data from the 15 outbreaks up until 2022, as well as an Approximate Bayesian Computational framework, were used to inform the model parameters.ResultsOur results show a low basic reproduction number which varied across outbreaks, from 0.5 [95% CI 0.05–1.8] to 1.2 [95% CI 1.0–1.9] but a high case fatality ratio. Of six vaccination strategies explored, the two prophylactic strategies (mass and targeted vaccination of high-risk groups), as well as a combination of ring and targeted vaccination, were generally most effective, with a probability of potential outbreaks being terminated within 1 year of 0.90 (95% CI 0.90–0.91), 0.89 (95% CI 0.88–0.90), and 0.88 (95% CI 0.87–0.89) compared with 0.68 (0.67–0.69) for no vaccination, especially if the outbreak is driven by zoonotic spillovers and the vaccination campaign initiated as soon as possible after onset of the first case.ConclusionsOur study shows that various vaccination strategies can be effective in helping to control outbreaks of MVD, with the best approach varying with the particular epidemiologic circumstances of each outbreak.

Discovery andgenome characterization ofsix new orthoparamyxoviruses insmall Belgian mammals.

In the future, zoonotic spillover events are expected to occur more frequently. Consequences of such events have clearly been demonstrated by recent outbreaks of monkeypox, Ebola virus, and the well-known severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Virus discovery has proven to be an important tool in the preparation against viral outbreaks, generating data concerning the diversity, quantity, and ecology of the vertebrate virome. Orthoparamyxoviruses, a subfamily within the Paramyxoviridae, are important biosurveillance targets, since they include several known animal, human, and zoonotic pathogens such as Nipah virus, measles virus, and Hendra virus. During this study, 127 bat samples, thirty-four rodent samples, and seventeen shrew samples originating from Belgium were screened for orthoparamyxovirus presence using nested reverse transcription-polymerase chain reaction assays and nanopore sequencing. We present here the complete genomes of six putative new viral species, belonging to the genera Jeilongvirus and Henipavirus. Characterization of these genomes revealed significant differences in gene composition and organization, both within viruses of the same genus and between viruses of different genera. Remarkably, a previously undetected gene coding for a protein of unknown function was identified in the genome of a putative new Henipavirus. Additionally, phylogenetic analysis of jeilongviruses and henipaviruses reveals a division of both genera into two clades, one consisting of bat-borne viruses and the other consisting of rodent- and shrew-borne viruses, elucidating the need for proper reclassification.