A global-scale dataset of bat viral detection suggests that pregnancy reduces viral shedding.

Understanding viral infection dynamics in wildlife hosts can help forecast zoonotic pathogen spillover and human disease risk. Bats are particularly important reservoirs of zoonotic viruses, including some of major public health concern such as Nipah virus, Hendra virus, and SARS-related coronaviruses. Previous work has suggested that metapopulation dynamics, seasonal reproductive patterns, and other bat life history characteristics might explain temporal variation in spillover of bat-associated viruses into people. Here, we analyze viral dynamics in free-ranging bat hosts, leveraging a multi-year, global-scale viral detection dataset that spans eight viral families and 96 bat species from 14 countries. We fit hierarchical Bayesian models that explicitly control for important sources of variation, including geographic region, specimen type, and testing protocols, while estimating the influence of reproductive status on viral detection in female bats. Our models revealed that late pregnancy had a negative effect on viral shedding across multiple data subsets, while lactation had a weaker influence that was inconsistent across data subsets. These results are unusual for mammalian hosts, but given recent findings that bats may have high individual viral loads and population-level prevalence due to dampening of antiviral immunity, we propose that it would be evolutionarily advantageous for pregnancy to either not further reduce immunity or actually increase the immune response, reducing viral load, shedding, and risk of fetal infection. This novel hypothesis would be valuable to test given its potential to help monitor, predict, and manage viral spillover risk from bats.

Global patterns and correlates in the emergence of antimicrobial resistance in humans.

Antimicrobial resistance (AMR) is a critical global health threat, and drivers of the emergence of novel strains of antibiotic-resistant bacteria in humans are poorly understood at the global scale. We examined correlates of AMR emergence in humans using global data on the origins of novel strains of AMR bacteria from 2006 to 2017, human and livestock antibiotic use, country economic activity and reporting bias indicators. We found that AMR emergence is positively correlated with antibiotic consumption in humans. However, the relationship between AMR emergence and antibiotic consumption in livestock is modified by gross domestic product (GDP), with only higher GDP countries showing a slight positive association, a finding that differs from previous studies on the drivers of AMR prevalence. We also found that human travel may play a role in AMR emergence, likely driving the spread of novel AMR strains into countries where they are subsequently detected for the first time. Finally, we used our model to generate a country-level map of the global distribution of predicted AMR emergence risk, and compared these findings against reported AMR emergence to identify gaps in surveillance that can be used to direct prevention and intervention policies.

Human interactions with bats and bat coronaviruses in rural Côte d'Ivoire.

Bats are presumed reservoirs of diverse α- and ß- coronaviruses (CoVs) and understanding the diversity of bat-CoVs and the role bats play in CoV transmission is highly relevant in the context of the current COVID pandemic. We sampled bats in Côte d'Ivoire (2016-2018) living at ecotones between anthropogenic and wild habitats in the Marahoué National Park, a recently encroached protected area, to detect and characterize the CoVs circulating in bats and humans. A total of 314 bats were captured, mostly during the rainy season (78%), and CoV RNA was detected in three of the bats (0.96%). A CoV RNA sequence similar to Chaerephon bat coronavirus/Kenya/KY22/2006 (BtKY22) was found in a Chaerephon cf. pumilus and a Mops sp. fecal swab, while a CoV RNA sequence similar to the two almost identical Kenya bat coronaviruses BtKY55 and BtKY56 (BtKY55/56) was detected in an Epomops buettikoferi oral swab. Phylogenetic analyses indicated differences in the degree of evolutionary host-virus co-speciation for BtKY22 and BtKY55/56. To assess potential for human exposure to these viruses, we conducted human syndromic and community-based surveillance in clinics and high-risk communities. We collected data on participant characteristics, livelihoods, animal contact, and high-risk behaviors that may be associated with exposure to zoonotic diseases. We then collected biological samples for viral testing from 401 people. PCR testing of these biological samples revealed no evidence of CoV infection among the enrolled individuals. We identified higher levels of exposure to bats in people working in crop production and in hunting, trapping and fishing. Finally, we used the 'Spillover' risk-ranking tool to assess the potential for viral spillover and concluded that, while there is no evidence to suggest imminent risk of spillover for these CoVs, their host range and other traits suggest caution and vigilance are warranted in people with high exposure risk.

Metagenomics-enabled reverse-genetics assembly and characterization of myotis bat morbillivirus.

Morbilliviruses are among the most contagious viral pathogens of mammals. Although previous metagenomic surveys have identified morbillivirus sequences in bats, full-length morbilliviruses from bats are limited. Here we characterize the myotis bat morbillivirus (MBaMV) from a bat surveillance programme in Brazil, whose full genome was recently published. We demonstrate that the fusion and receptor binding protein of MBaMV utilize bat CD150 and not human CD150, as an entry receptor in a mammalian cell line. Using reverse genetics, we produced a clone of MBaMV that infected Vero cells expressing bat CD150. Electron microscopy of MBaMV-infected cells revealed budding of pleomorphic virions, a characteristic morbillivirus feature. MBaMV replication reached 103-105 plaque-forming units ml-1 in human epithelial cell lines and was dependent on nectin-4. Infection of human macrophages also occurred, albeit 2-10-fold less efficiently than measles virus. Importantly, MBaMV is restricted by cross-neutralizing human sera elicited by measles, mumps and rubella vaccination and is inhibited by orally bioavailable polymerase inhibitors in vitro. MBaMV-encoded P/V genes did not antagonize human interferon induction. Finally, we show that MBaMV does not cause disease in Jamaican fruit bats. We conclude that, while zoonotic spillover into humans may theoretically be plausible, MBaMV replication would probably be controlled by the human immune system.

Identification and Genetic Characterization of MERS-Related Coronavirus Isolated from Nathusius' Pipistrelle (Pipistrellus nathusii) near Zvenigorod (Moscow Region, Russia).

Being diverse and widely distributed globally, bats are a known reservoir of a series of emerging zoonotic viruses. We studied fecal viromes of twenty-six bats captured in 2015 in the Moscow Region and found 13 of 26 (50%) samples to be coronavirus positive. Of P. nathusii (the Nathusius' pipistrelle), 3 of 6 samples were carriers of a novel MERS-related betacoronavirus. We sequenced and assembled the complete genome of this betacoronavirus and named it MOW-BatCoV strain 15-22. Whole genome phylogenetic analysis suggests that MOW-BatCoV/15-22 falls into a distinct subclade closely related to human and camel MERS-CoV. Unexpectedly, the phylogenetic analysis of the novel MOW-BatCoV/15-22 spike gene showed the closest similarity to CoVs from Erinaceus europaeus (European hedgehog). We suppose MOW-BatCoV could have arisen as a result of recombination between ancestral viruses of bats and hedgehogs. Molecular docking analysis of MOW-BatCoV/15-22 spike glycoprotein binding to DPP4 receptors of different mammals predicted the highest binding ability with DPP4 of the Myotis brandtii bat (docking score -320.15) and the E. europaeus (docking score -294.51). Hedgehogs are widely kept as pets and are commonly found in areas of human habitation. As this novel bat-CoV is likely capable of infecting hedgehogs, we suggest hedgehogs can act as intermediate hosts between bats and humans for other bat-CoVs.

Nipah Virus Exposure in Domestic and Peridomestic Animals Living in Human Outbreak Sites, Bangladesh, 2013-2015.

Spillovers of Nipah virus (NiV) from Pteropus bats to humans occurs frequently in Bangladesh, but the risk for spillover into other animals is poorly understood. We detected NiV antibodies in cattle, dogs, and cats from 6 sites where spillover human NiV infection cases occurred during 2013-2015.

Prevalence of bat viruses associated with land-use change in the Atlantic Forest, Brazil.

Introduction: Bats are critical to maintaining healthy ecosystems and many species are threatened primarily due to global habitat loss. Bats are also important hosts of a range of viruses, several of which have had significant impacts on global public health. The emergence of these viruses has been associated with land-use change and decreased host species richness. Yet, few studies have assessed how bat communities and the viruses they host alter with land-use change, particularly in highly biodiverse sites. Methods: In this study, we investigate the effects of deforestation on bat host species richness and diversity, and viral prevalence and richness across five forested sites and three nearby deforested sites in the interior Atlantic Forest of southern Brazil. Nested-PCR and qPCR were used to amplify and detect viral genetic sequence from six viral families (corona-, adeno-, herpes-, hanta-, paramyxo-, and astro-viridae) in 944 blood, saliva and rectal samples collected from 335 bats. Results: We found that deforested sites had a less diverse bat community than forested sites, but higher viral prevalence and richness after controlling for confounding factors. Viral detection was more likely in juvenile males located in deforested sites. Interestingly, we also found a significant effect of host bat species on viral prevalence indicating that viral taxa were detected more frequently in some species than others. In particular, viruses from the Coronaviridae family were detected more frequently in generalist species compared to specialist species. Discussion: Our findings suggest that deforestation may drive changes in the ecosystem which reduce bat host diversity while increasing the abundance of generalist species which host a wider range of viruses.

Pandemic origins and a One Health approach to preparedness and prevention: Solutions based on SARS-CoV-2 and other RNA viruses.

COVID-19 is the latest zoonotic RNA virus epidemic of concern. Learning how it began and spread will help to determine how to reduce the risk of future events. We review major RNA virus outbreaks since 1967 to identify common features and opportunities to prevent emergence, including ancestral viral origins in birds, bats, and other mammals; animal reservoirs and intermediate hosts; and pathways for zoonotic spillover and community spread, leading to local, regional, or international outbreaks. The increasing scientific evidence concerning the origins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is most consistent with a zoonotic origin and a spillover pathway from wildlife to people via wildlife farming and the wildlife trade. We apply what we know about these outbreaks to identify relevant, feasible, and implementable interventions. We identify three primary targets for pandemic prevention and preparedness: first, smart surveillance coupled with epidemiological risk assessment across wildlife-livestock-human (One Health) spillover interfaces; second, research to enhance pandemic preparedness and expedite development of vaccines and therapeutics; and third, strategies to reduce underlying drivers of spillover risk and spread and reduce the influence of misinformation. For all three, continued efforts to improve and integrate biosafety and biosecurity with the implementation of a One Health approach are essential. We discuss new models to address the challenges of creating an inclusive and effective governance structure, with the necessary stable funding for cross-disciplinary collaborative research. Finally, we offer recommendations for feasible actions to close the knowledge gaps across the One Health continuum and improve preparedness and response in the future.

A strategy to assess spillover risk of bat SARS-related coronaviruses in Southeast Asia.

Emerging diseases caused by coronaviruses of likely bat origin (e.g., SARS, MERS, SADS, COVID-19) have disrupted global health and economies for two decades. Evidence suggests that some bat SARS-related coronaviruses (SARSr-CoVs) could infect people directly, and that their spillover is more frequent than previously recognized. Each zoonotic spillover of a novel virus represents an opportunity for evolutionary adaptation and further spread; therefore, quantifying the extent of this spillover may help target prevention programs. We derive current range distributions for known bat SARSr-CoV hosts and quantify their overlap with human populations. We then use probabilistic risk assessment and data on human-bat contact, human viral seroprevalence, and antibody duration to estimate that a median of 66,280 people (95% CI: 65,351-67,131) are infected with SARSr-CoVs annually in Southeast Asia. These data on the geography and scale of spillover can be used to target surveillance and prevention programs for potential future bat-CoV emergence.

Classification of new morbillivirus and jeilongvirus sequences from bats sampled in Brazil and Malaysia.

As part of a broad One Health surveillance effort to detect novel viruses in wildlife and people, we report several paramyxovirus sequences sampled primarily from bats during 2013 and 2014 in Brazil and Malaysia, including seven from which we recovered full-length genomes. Of these, six represent the first full-length paramyxovirid genomes sequenced from the Americas, including two that are the first full-length bat morbillivirus genome sequences published to date. Our findings add to the vast number of viral sequences in public repositories, which have been increasing considerably in recent years due to the rising accessibility of metagenomics. Taxonomic classification of these sequences in the absence of phenotypic data has been a significant challenge, particularly in the subfamily Orthoparamyxovirinae, where the rate of discovery of novel sequences has been substantial. Using pairwise amino acid sequence classification (PAASC), we propose that five of these sequences belong to members of the genus Jeilongvirus and two belong to members of the genus Morbillivirus. We also highlight inconsistencies in the classification of Tupaia virus and Mòjiang virus using the same demarcation criteria and suggest reclassification of these viruses into new genera. Importantly, this study underscores the critical importance of sequence length in PAASC analysis as well as the importance of biological characteristics such as genome organization in the taxonomic classification of viral sequences.

Knowledge, attitudes, and practices associated with zoonotic disease transmission risk in North Sulawesi, Indonesia.

BACKGROUND: Hunters, vendors, and consumers are key actors in the wildlife trade value chain in North Sulawesi, Indonesia, and potentially face an elevated risk of exposure to zoonotic diseases. Understanding the knowledge, attitudes, and practices (KAP) associated with the risk of zoonotic disease transmission in these communities is therefore critical for developing recommendations to prevent or mitigate zoonotic outbreaks in the future. METHODS: Qualitative and quantitative methods were combined to understand KAP associated zoonotic diseases transmission risk in communities involved in the wildlife trade in North Sulawesi. Qualitative data were collected through semi-structured ethnographic interviews and focus group discussions (FGDs) while quantitative data were collected using questionnaires. We conducted 46 ethnographic interviews and 2 FGDs in 2016, and 477 questionnaire administrations in 2017-2018 in communities from five districts in North Sulawesi. We also collected biological specimens, including nasal swab, oropharyngeal swab, and blood, from 254 participants. The study sites were targeted based on known wildlife consumption and trade activities. The participants for qualitative data collection were purposively selected while participants for quantitative data collection were randomly selected. Biological samples were tested for five viral families including Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. RESULTS: Knowledge regarding disease transmission from animals to humans was similar across the participants in qualitative focus groups, including knowledge of rabies and bird flu as zoonotic diseases. However, only a small fraction of the participants from the quantitative group (1%) considered that contact with wild animals could cause sickness. Our biological specimen testing identified a single individual (1/254, 0.004%) who was sampled in 2018 with serological evidence of sarbecovirus exposure. Overall, participants were aware of some level of risk in working with open wounds while slaughtering or butchering an animal (71%) but most did not know what the specific risks were. However, significant differences in the attitudes or beliefs around zoonotic disease risk and health seeking behaviors were observed across our study sites in North Sulawesi. CONCLUSIONS: Our study showed variable levels of knowledge, attitudes, and practices associated with the risk of zoonotic disease transmission among study participants. These findings can be used to develop locally responsive recommendations to mitigate zoonotic disease transmission.

Nipah Virus Detection at Bat Roosts after Spillover Events, Bangladesh, 2012-2019.

Knowledge of the dynamics and genetic diversity of Nipah virus circulating in bats and at the human-animal interface is limited by current sampling efforts, which produce few detections of viral RNA. We report a series of investigations at Pteropus medius bat roosts identified near the locations of human Nipah cases in Bangladesh during 2012-2019. Pooled bat urine was collected from 23 roosts; 7 roosts (30%) had >1 sample in which Nipah RNA was detected from the first visit. In subsequent visits to these 7 roosts, RNA was detected in bat urine up to 52 days after the presumed exposure of the human case-patient, although the probability of detection declined rapidly with time. These results suggest that rapidly deployed investigations of Nipah virus shedding from bat roosts near human cases could increase the success of viral sequencing compared with background surveillance and could enhance understanding of Nipah virus ecology and evolution.

Behavioral-biological surveillance of emerging infectious diseases among a dynamic cohort in Thailand.

BACKGROUND: Interactions between humans and animals are the key elements of zoonotic spillover leading to zoonotic disease emergence. Research to understand the high-risk behaviors associated with disease transmission at the human-animal interface is limited, and few consider regional and local contexts. OBJECTIVE: This study employed an integrated behavioral-biological surveillance approach for the early detection of novel and known zoonotic viruses in potentially high-risk populations, in an effort to identify risk factors for spillover and to determine potential foci for risk-mitigation measures. METHOD: Participants were enrolled at two community-based sites (n = 472) in eastern and western Thailand and two hospital (clinical) sites (n = 206) in northeastern and central Thailand. A behavioral questionnaire was administered to understand participants' demographics, living conditions, health history, and animal-contact behaviors and attitudes. Biological specimens were tested for coronaviruses, filoviruses, flaviviruses, influenza viruses, and paramyxoviruses using pan (consensus) RNA Virus assays. RESULTS: Overall 61/678 (9%) of participants tested positive for the viral families screened which included influenza viruses (75%), paramyxoviruses (15%), human coronaviruses (3%), flaviviruses (3%), and enteroviruses (3%). The most salient predictors of reporting unusual symptoms (i.e., any illness or sickness that is not known or recognized in the community or diagnosed by medical providers) in the past year were having other household members who had unusual symptoms and being scratched or bitten by animals in the same year. Many participants reported raising and handling poultry (10.3% and 24.2%), swine (2%, 14.6%), and cattle (4.9%, 7.8%) and several participants also reported eating raw or undercooked meat of these animals (2.2%, 5.5%, 10.3% respectively). Twenty four participants (3.5%) reported handling bats or having bats in the house roof. Gender, age, and livelihood activities were shown to be significantly associated with participants' interactions with animals. Participants' knowledge of risks influenced their health-seeking behavior. CONCLUSION: The results suggest that there is a high level of interaction between humans, livestock, and wild animals in communities at sites we investigated in Thailand. This study highlights important differences among demographic and occupational risk factors as they relate to animal contact and zoonotic disease risk, which can be used by policymakers and local public health programs to build more effective surveillance strategies and behavior-focused interventions.

URSID γ-HERPESVIRUS TYPE 1-RELATED VIRUS IN CAPTIVE BORNEAN SUN BEARS (HELARCTOS MALAYANUS EURYSPILUS) IN SABAH, MALAYSIA.

The Bornean sun bear (Helarctos malayanus euryspilus) is the smallest subspecies of sun bear. Their numbers are declining, and more research is needed to better understand their health and biology. Forty-four bears housed at the Bornean Sun Bear Conservation Centre (BSBCC) in Sabah, Malaysia, were screened for known and novel viruses in November 2018. Ursid γ-herpesvirus type 1 (UrHV-1) is a herpesvirus that has been detected from swab samples of clinically healthy sun bears and biopsy samples of oral squamous cell carcinoma in sun bears. We detected an UrHV-1-related virus from throat and rectal swabs by molecular viral screening in samples from 15.9% of the sun bears at BSBCC. None of the bears with the UrHV-1-related virus in this study had oral lesions. There is no known report of UrHV-1 detection in the wild sun bear population, and its association with oral squamous cell carcinoma is not fully understood. Finding an UrHV-1-related virus in a rehabilitation center is a concern because conditions in captivity may contribute to spreading this virus, and there is the potential of introducing it into wild populations when a bear is released. This study demonstrates an urgent need to carry out similar surveillance for sun bears in captivity as well as those in the wild, to better understand the impact of captivity on the prevalence and spread of UrHV-1-related viruses. Positive bears also should be monitored for oral lesions to better understand whether there is a causal relationship.

Investing to Both Prevent and Prepare for COVID-XX.

One cause of the high rate of COVID-19 cases in the USA is thought to be insufficient prior capital investment in national health programs to preemptively reduce the likelihood of an outbreak and in national capacity to reduce the severity of any outbreak that does occur. We analyze the choice of capital investments (e.g. testing capacity, stockpiles of PPE, and information sharing capacity) and find the economically efficient capital stock associated with mitigating pandemic risk should be dramatically expanded. Policymakers who fail to invest in public health forgo significant expected cost savings from being prepared.

The costs and benefits of primary prevention of zoonotic pandemics.

The lives lost and economic costs of viral zoonotic pandemics have steadily increased over the past century. Prominent policymakers have promoted plans that argue the best ways to address future pandemic catastrophes should entail, "detecting and containing emerging zoonotic threats." In other words, we should take actions only after humans get sick. We sharply disagree. Humans have extensive contact with wildlife known to harbor vast numbers of viruses, many of which have not yet spilled into humans. We compute the annualized damages from emerging viral zoonoses. We explore three practical actions to minimize the impact of future pandemics: better surveillance of pathogen spillover and development of global databases of virus genomics and serology, better management of wildlife trade, and substantial reduction of deforestation. We find that these primary pandemic prevention actions cost less than 1/20th the value of lives lost each year to emerging viral zoonoses and have substantial cobenefits.

Living Safely With Bats: Lessons in Developing and Sharing a Global One Health Educational Resource.

As part of a public health behavior change and communication strategy related to the identification of a novel ebolavirus in bats in Sierra Leone in 2016, a consortium of experts launched an effort to create a widely accessible resource for community awareness and education on reducing disease risk. The resulting picture book, Living Safely With Bats, includes technical content developed by a consortium of experts in public health, animal health, conservation, bats, and disease ecology from 30 countries. The book has now been adapted, translated, and used in more than 20 countries in Africa and Asia. We review the processes used to integrate feedback from local stakeholders and multidisciplinary experts. We also provide recommendations for One Health and other practitioners who choose to pursue the development and evaluation of this or similar zoonotic disease risk mitigation tools.