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Zoonotic diseases (ZD) are those infections that can be naturally transmitted from animals to humans with or without vector. In the past few decades, there has been a rise in the outbreaks of zoonotic diseases which have an enormous socioeconomic impact worldwide, for instance, all foodborne zoonoses occured in a single country costs about $1.3 billion annually. Additionally, ZD constitute 61% of all communicable diseases causing illness in humans and about 75% of emerging human pathogens. More than 75% of the diseases that affected humans have been transmitted from animals or animal products. Zoonotic diseases can be transferred from animals to humans by several ways such as the consumption of contaminated food and water (e.g., cryptosporidiosis), exposure to the pathogen during processing (e.g., campylobacteriosis and salmonellosis), direct contact with infected animals (e.g., avian influenza) and by pets scratches or bite (e.g., rabies). Some emerging zoonoses expanded their host range and their incidence increased (e.g., avian influenza). This expansion occurred as a result of global trade, increase poultry production, climate changes, bird migration, human movement, and the burgeoning global population. Several animal reservoirs of ZD have been identified, including ruminants, equines, poultry, rodents, dogs and cats, mosquitoes and ticks, which were considered a potential risk of disease transmission. Furthermore, antimicrobial resistance considered as an additional risk associated with exposure to zoonotic pathogens because it is potentially limits disease treatment options in both public health and veterinary settings. Therefore, prevention and control programs should be implemented by public health and veterinary officers to combat the sources and reservoirs of zoonoses especially after the development of antimicrobial resistance problem due to misuse of antibiotics.
Egypt is located in the north-eastern part of Africa connecting the three old-world continents Africa, Asia and Europe. It is the county with the highest population density in the Middle East, North Africa and the Mediterranean basin with about 90 million inhabitants. Egypt has 27 governorates and over 90% of the population live in 10% of the whole area along the River Nile and Nile Delta in the northern part of the country. A number of zoonotic pathogens have been reported in Egypt. The burden of ZD is provoked by factors such as the method of control, environmental factors, behavioral factors, social factors, clinical manifestations, the socioeconomic impact of such diseases and mode of transmission. The highest incidence and prevalence of zoonotic diseases in Egypt may be attributed to the deficiency of suitable control mechanisms, inadequate infrastructure and lack of information on their significance and distribution. However, there is a marked decrease in the prevalence of some ZD (e.g., schistosomiasis). In this review, we will focus on the most important and prevalent emerging and re-emerging ZD in Egypt including the current situation, reservoirs, sources of human infection and control regimes, if available.
Zoonotic infectious diseases – diseases transmitted from vertebrate animals to humans – account for an estimated 60% of all human infectious diseases. The rise of zoonotic diseases in humans began after the introduction of agriculture and the domestication of animals when humans started living in large numbers together, in close contact with other vertebrate animals,. Nowadays, livestock associated infectious diseases are still a major threat to human health, as recently illustrated by the outbreak of pig origin H1N1 influenza A pandemic in 2009 or the emergence of camel-origin Middle-East Respiratory Syndrome Coronavirus,,. The occurrence of a zoonotic disease may lead to large economic losses in the agricultural sector,,,,,,,. When it comes to recent emerging infectious diseases, zoonoses again account for the majority of the newly introduced infectious diseases to the human population. Although zoonoses with a wildlife origin dominate among emerging pathogens, livestock associated zoonotic diseases occur mainly in densely human populated areas in the world and can therefore have a considerable public health impact. In developing countries humans often live close to their livestock,,; in developed countries there are mainly occupational contacts with large numbers of live, ill or dead animals,,,, but there are also reports of micro-organism transmissions via the environment, or after brief contact,.
Contact with livestock animals can lead to transmission of micro-organisms by inhalation, ingestion, via conjunctiva, or during incidents such as biting or other injuries inflicted by animals. Furthermore, aerosols contaminated with micro-organisms from respiratory,,,, or fluid sources, can play an important role in the transmission of micro-organisms between humans,,,,,, but also from animals to humans. Aerosols have been suggested to play a role in micro-organism transmission over very short distances, sometimes as a parallel route to direct contact. It is thus clear that for transmission of zoonotic diseases to occur, the presence of animals or some type of contact with (livestock-) animals is crucial. Initiatives to control livestock-associated zoonotic diseases are already in place, as reviewed by Zinnstag et al. and others,. However, better understanding of contact patterns driving micro-organism transmission from animals to humans is needed to provide options for prevention and thus deserves more attention. Therefore, in this study we reviewed current literature on livestock-associated zoonotic diseases, to evaluate current knowledge regarding human–livestock contact patterns. We conducted a systematic review to identify papers reporting on livestock-related zoonoses. We searched the publications regarding reports of contact patterns between livestock animals and humans that led to a transmission of infectious diseases or micro-organisms from livestock to man.
Zoonotic diseases are those infections that can be transmitted between animals and humans with or without vectors. There are approximately 1500 pathogens, which are known to infect humans and 61% of these cause zoonotic diseases (1). The unique dynamic interaction between the humans, animals, and pathogens, sharing the same environment should be considered within the “One Health” approach, which dates back to ancient times of Hippocrates (2, 3).
Bacterial zoonotic diseases can be transferred from animals to humans in many ways (4): (i) The transfer may occur through animal bites and scratches (5); (ii) zoonotic bacteria originating from food animals can reach people through direct fecal oral route, contaminated animal food products, improper food handling, and inadequate cooking (6–8); (iii) farmers and animal health workers (i.e., veterinarians) are at increased risk of exposure to certain zoonotic pathogens and they may catch zoonotic bacteria; they could also become carriers of the zoonotic bacteria that can be spread to other humans in the community (9); (iv) vectors, frequently arthropods, such as mosquitoes, ticks, fleas, and lice can actively or passively transmit bacterial zoonotic diseases to humans. (10); (v) soil and water recourses, which are contaminated with manure contains a great variety of zoonotic bacteria, creating a great risk for zoonotic bugs and immense pool of resistance genes that are available for transfer of bacteria that cause human diseases (11, 12).
Bacterial zoonotic infections are one of the zoonotic diseases, which can, in particular, re-emerge after they are considered to be eradicated or under control. The development of antimicrobial resistance due to over-/misuse of antibiotics is also a globally increasing public health problem. These diseases have a negative impact on travel, commerce, and economies worldwide. In most industrialized countries, antibiotic resistant zoonotic bacterial diseases are of particular importance for at-risk groups such as young, old, pregnant, and immune-compromised individuals (13).
Almost 100 years ago, prior to application of hygiene rules and discovery of neither vaccines nor antibiotics, some bacterial zoonotic diseases such as bovine tuberculosis, bubonic plague, and glanders caused millions of human deaths. The spread and importance of some bacterial zoonoses are currently globally increasing. That is precisely why most of the developing countries are sparing more resources for a better screening of animal products and bacterial reservoirs or vectors for an optimal preventative public health service (14).
Improvements in surveillance and diagnostics have caused increased recognition of emerging zoonotic diseases. Herein, changes in our lifestyles and closer contacts with animals have escalated or caused the re-emergence of some bacterial infections. Some studies lately have revealed that people have never been exposed to bacterial zoonotic infection risks as high as this before (15). It is probably due to closer contact with adopted small animals, which are accepted and treated as a family member in houses. On the other hand, more intensified animal farms, which have a crucial role in the food supply, are still one of the greatest sources of food-borne bacterial zoonotic pathogens in today’s growing world (4, 8).
People who have closer contact with large numbers of animals such as farmers, abattoir workers, zoo/pet-shop workers, and veterinarians are at a higher risk of contracting a zoonotic disease. Members of the wider community are also at risk from those zoonoses that can be transmitted by family pets.
The immune-suppressed people are especially at high risk for infection with zoonotic bacterial diseases. People can be either temporarily immuno-suppressed owing to pregnancy, infant age, or long-term immuno-suppressed as a result of cancer treatment or organ transplant, diabetes, alcoholism or an infectious disease (i.e., AIDS).
This manuscript reviews the most common bacterial zoonoses and practical control measures against them.
The global discovery of lyssaviruses is of continued scientific interest and is of importance to both public and animal health. Lyssaviruses are known to cause fatal encephalitis, referred to as rabies. The term rabies has induced terror throughout human history, as the rabies virus (RABV) is the only viral pathogen that is associated with 100% fatality following the onset of the clinical disease. Whilst rabies is predominantly circulating within domestic and feral dog populations globally, the presence of lyssaviruses in bats is well established. Historically, rabies’ association with hematophagous bats (Desmodus sp., although primarily Desmodus rotundus) across the Caribbean, and Central and South America, has both embedded a fear of rabies into human populations, as well as driven an irrational and unjustified fear of bats across many cultures. Certainly, bat transmitted human RABV is rare, although in areas where terrestrial rabies has been eliminated, bat rabies remains a constant threat, as exemplified by continued human cases of bat rabies across North America. In endemic areas, human infection with dog rabies results in thousands of human deaths annually. The estimates of human infection are thought to be conservative, because of inadequate diagnostic and reporting systems across Africa and Asia. Wildlife species can also play an important role in the epidemiology of disease, although the paucity of data on wild animal populations, their distribution, and the generally sporadic interactions between different wildlife populations and domesticated carnivore species means that the role of wildlife and the epidemiology of the virus is often unclear. Still, the transmission of the virus between wildlife and domestic terrestrial carnivores is multidirectional, with incursions of domestic dog rabies into fox populations being reported.
The severity of disease caused by lyssaviruses means that the potential for cross species transmission events (CSTs) is of significance to human and animal populations. For the rabies virus, spill over events are considered as those that result in dead-end infection, whilst CSTs result in the sustained onward transmission of the virus in the new host. Spill over from bats species appears common for RABV in the Americas, whilst events involving the other lyssaviruses across the Old World appear to be rare. Whilst spill over events for lyssaviruses have been reported, host switching events are far rarer and have only been described for RABV in the Americas. The factors involved in CSTs with the sustained onward transmission of the virus remain undefined, and endeavours to identify specific amino acid substitutions facilitating virus adaptation to new host species have been, on the most part, unsuccessful. Kuzmin et al. (2012) observed that for sustainability within a bat population, a Serine at position 242 in the viral G protein appeared to predominate, and that contrastingly, an Alanine/Threonine substitution at position 242 appears to facilitate RABV sustainability within the carnivore population. Intensive characterisation of the genetics within viral populations, including quasispecies, may elucidate the molecular mechanisms that facilitate lyssavirus adaption, however opportunities to genetically characterise such events are rare.
Endemic zoonoses such as brucellosis (Brucella species), Q fever (Coxiella burnetii), leptospirosis (Leptospira species), rickettsioses (Rickettsia species), bartonellosis (Bartonella species), plague (Yersinia pestis), Rift Valley fever and Chikungunya (both caused by arboviruses), and many others, pose considerable challenges for clinicians in both human and animal health. They frequently present with general symptoms that are shared with a wide range of infectious diseases common in the tropics, and are hard to identify or differentiate clinically. As a consequence, the true burden of endemic zoonoses is largely underappreciated and awareness among clinicians and policymakers remains limited.
In humans, non-specific symptoms such as fever, headache, fatigue, and joint or muscle aches are commonly associated with many endemic zoonoses. These symptoms also occur with common non-zoonotic diseases, such as malaria and typhoid fever, which are likely to be considered more readily by clinicians (Crump 2012, 2014). Considerable social influences, such as training context, the influence of peers, and pressure to meet patient expectations, can also contribute to the overdiagnosis of diseases such as malaria, and thus to the relative underdiagnosis of other diseases including many zoonoses (Chandler and others 2008). Even well-recognised zoonotic diseases with distinctive clinical signs may be misdiagnosed as malaria. For example, in a study of childhood encephalitis in a malaria-endemic region of Malawi, rabies was confirmed as the cause of 10.5 per cent of fatal cases of encephalitis. Several of these cases were originally attributed to cerebral malaria, with clinical manifestations indistinguishable from those of cerebral malaria, but with subsequent histological examination showing no evidence of sequestration of parasitised erythrocytes in cerebral tissues (a hallmark of cerebral malaria) (Mallewa and others 2007).
More specific symptoms may occur with some zoonotic diseases, but these lack sensitivity or specificity, so cannot be relied upon for a clinical diagnosis. For example, hepatomegaly and splenomegaly are often reported in cases of human brucellosis (World Health Organization [WHO] and others 2006), but vary in the degree to which they are observed within and between different populations (Bouley and others 2012, Dean and others 2012a). In northern Tanzania, 18.8 per cent of patients with a confirmed diagnosis of acute brucellosis also had hepato- or splenomegaly on physical examination (Bouley and others 2012). Similarly, pneumonia is often considered one of the main presentations of Q fever in humans; however, in a hospital-based study in Taiwan, only 13.5 per cent of confirmed cases of acute Q fever presented with respiratory symptoms (Lai and others 2014).
Epilepsy is one of the most common neurological conditions in Africa, estimated to affect 4.4 million people and having significant physical, economic and social consequences (Paul and others 2012). Neurocysticercosis, caused by the tapeworm Taenia solium, is increasingly recognised as a major cause of epilepsy, with a meta-analysis of studies in Latin America, India and sub-Saharan Africa identifying neurocysticercosis as the cause of 30 per cent cases of epilepsy (Ndimubanzi and others 2010). Other endemic parasitic zoonoses that contribute to neurological syndromes in the tropics include Trypanosoma brucei rhodesiense, the zoonotic cause of human African sleeping sickness; and toxoplasmosis, which is the leading cause of central nervous system (CNS) disease in HIV-infected patients. A wide range of zoonotic parasitic diseases, including echinococcosis and trichinosis, as well as non-parasitic zoonoses, such as leptospirosis and borreliosis, also have the potential to cause a range of CNS signs, and may contribute to the burden of neurological disease in endemic areas.
The challenge of non-specific presentation of many zoonoses also applies to the diagnosis of animal infection. For some zoonoses, for example Escherichia coli O157 in livestock and T brucei rhodesiense in wildlife, zoonotic infections often cause no apparent clinical signs in the animal host. Even where clinical signs of disease are seen (for example, with Q fever, brucellosis and leptospirosis), the level of disease recognition and reporting is likely to be several fold lower in livestock than in humans, ensuring that animal healthcare providers often have even less observational data to inform diagnoses than their medical colleagues.
Abortions are often one of the most readily recognisable signs of infectious illness in livestock and can have severe impacts on individual animal and herd productivity. Data concerning the incidence of livestock abortions and other productivity measures are frequently lacking in livestock-dependent settings. However, a study in northern Tanzania reported abortion events in 19 per cent of cattle herds, and 33 per cent of sheep/goat flocks, with 12.9 per cent of female domestic ruminants having a history of at least one abortion (Shirima 2005). Infection with several of the priority zoonoses of the World Organisation for Animal Health (OIE), including Brucella, Leptospira and Streptococcus species, Campylobacter, Chlamydia, Ehrlichia, Anaplasma, Borrelia burgdorferi and C burnetii can cause abortion in livestock species and other animals. The fact that so many zoonoses affecting people in the tropics also cause abortion in livestock suggests that there is likely to be great value in One Health approaches that link aetiological and epidemiological studies of livestock abortion with research on common human health syndromes.
Human microbiologic infections, known as zoonoses, are acquired directly from animals or via arthropods bites and are an increasing public health problem. More than two thirds of emerging human pathogens are of zoonotic origin, and of these, more than 70% originate from wildlife. In novel environments, viruses, particularly RNA viruses, can easily cross the species barrier by mutations, recombinations or reassortments of their genetic material, resulting in the capacity to infect novel hosts. Because of their adaptive abilities, RNA viruses represent more than 70% of the viruses that infect humans. When socio-economic and ecologic changes affect their environment, humans may encounter increased contact with emerging viruses that originate in wild or domestic animals.
Wolfe et al. in 2007 and Karesh et al. in 2012 described different stages in the switch from an animal-specific infectious agent into a human-specific pathogen. The key stage is the transition of a strictly animal-specific infectious agent (originating from wildlife or domestic animals) to exposed human populations, resulting in sporadic human infections (Figure 1). If the pathogen is able to adapt to its human host and acquire the means to accomplish an inter-human transmission, horizontal human-to-human transmission occurs and maintains the viral cycle. Sometimes, an intermediate host, such as a domestic animal, is the link between sylvatic viral circulation and human viral circulation. For example, some human infections originating from bats, such as Nipah, Hendra, SARS and Ebola viral infections, may involve intermediate amplification in hosts such as pigs, horses, civets and primates, respectively (Figure 1). Genetic, biologic, social, political or economic factors may explain a switch in viral host targets. For example, climate changes may influence the geographical repartition of vector arthropods, leading to new areas of the distribution of infectious diseases, like Aedes albopictus and Chikungunya infections in the Mediterranean. Morens et al. listed different key factors that may contribute to the emergence or re-emergence of infectious diseases, such as microbial adaptation to a new environment, biodiversity loss, ecosystem changes that lead to more frequent contact between wildlife and domestic animals or human populations, human demographics and behavior, economic development and land use, international travel and commerce, etc.. These patterns of transmission allow identifying different animals to follow in order to monitor the appearance of new or re-emerging infectious agents before its first detection in the human populations. Therefore, hematophagous arthropods, wildlife and domestic animals may serve as targets for zoonotic and arboviral disease surveillance, particularly because sampling procedures and long-term follow-up studies are more easily performed in these hosts than in humans.
Historically, classic viral detection techniques were based on the intracerebral inoculation of suckling mice or viral isolation in culture and the subsequent observation of cytopathic effects on cell lines. Later, immunologic methods, e.g., seroneutralization or hemaglutination, were used to detect viral antigens in various complex samples. These techniques were based on the isolation of viral agents. With the progresses of molecular biology, polymerase chain reaction (PCR)-based methods became the main techniques for virus discovery and allowed the detection of uncultivable viruses, but these techniques required prior knowledge of closely related viral genomes. Next-Generation Sequencing (NGS) techniques make it possible to sequence all viral genomes in a given sample without previous knowledge about their nature. These techniques, known as viral metagenomics, have allowed the discovery of completely new viral species. Because of their low cost, the use of NGS techniques is exponentially increasing.
The transmission of infections between humans occurs after a pathogen from a wild or domestic animal contacts with exposed human populations. The human exposures may or may not be mediated by the bite of bloodsucking arthropods. Surveillance programs may target wildlife, domestic animals or arthropods for emerging viruses before their adaptation to human hosts.
Among emerging zoonotic wildlife diseases, vector-borne infections pose a major challenge to public health both in terms of vector and pathogen abundance and diversity and of human and animal morbidity and mortality. Furthermore, the continuous discovery of new pathogens and the emergence of new epidemiological cycles, due for example to the invasion of new habitat by vector species, claim the need for a constant and intensified surveillance.
In general, vector-borne pathogens account for more than 17% of all infectious diseases, causing more than 700 000 deaths annually (https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases, accessed May 27, 2019). The burden of these diseases is highest in tropical and subtropical areas where especially mosquito-borne diseases disproportionately affect the poorest populations. In such areas, major outbreaks of dengue, malaria, chikungunya, yellow fever and more recently Zika have been afflicting populations, claimed lives and overwhelmed health systems. Other diseases such as Chagas disease and leishmaniosis affect hundreds of millions of people worldwide (https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases, accessed May 27, 2019).
Within the temperate areas of the northern hemisphere wildlife zoonoses carried by ticks pose the greatest challenge when compared to mosquito-borne infection. In general, reported cases of vector-borne infections have increased during the last 30 years in the northern hemisphere (Semenza and Suk, 2018). In Europe, the most challenging infections include Ixodes ricinus transmitted diseases such as Lyme borreliosis (LB) and Tick-borne encephalitis (TBE) with an average number of 85.000 and 16.000 cases reported annually respectively. Other tick-borne diseases with rising public health concern include rickettsiosis and Crimean-Congo Hemorrhagic Fever. Mosquito borne diseases of concern include viral infection induced by WNV, Usutu virus (USUV) and Chikungunya virus (CHIKV), while others (i.e. dengue virus, Plasmodium spp.) still represent a potential threat with few sporadic autochthonous episodes of local circulation, especially within the countries of the Mediterranean basin.
A similar trend has been reported for the USA where cases of mosquito-borne and tick-borne diseases have more than tripled since 2004, characterized by steadily increasing incidence of tick-borne diseases and sporadic outbreaks of domestic and invasive mosquito-borne diseases (Petersen et al., 2019).
Transmission of vector-borne pathogens is particularly sensitive to anthropogenic changes as they imply the interaction of three principal players: the pathogen, the vector (represented in many cases by an invertebrate) and a vertebrate host which can acquire and transmit the infection, if competent. Changes in vector-host interaction and in the vectorial capacity can determine a rise in infection hazard and disease incidence.
Companion animals are increasingly treated as family members, and pets have many bacteria that may infect their owners. The human population of the European Union (EU) was approximately 500 million1 in 2012. The number of pet owning households was estimated at around 70 million in 20102.
The most commonly suffered zoonotic bacterial infections in humans are transmitted via animal bites and scratches. Various dog breeds have been characterized for their role in killing dog bite attacks, such as pit bull breeds, malamutes, chows, rottweiler, huskies, German shepherds, and wolf hybrids (16–18). In USA, pit bull breeds accounted for almost half of the dog bite-related zoonotic infections, three times more than German shepherds (17). The oral cavity of healthy dogs and cats contains hundreds of different pathogenic bacteria including Pasteurella sp. (19). Only 20% of dog bites get infected overall compared with 60% in cats. There are 10 times higher Pasteurella multocida infection risks after a cat bite than a dog bite (20, 21). P. multocida infected bite wounds appear usually within 8 h.
It is estimated that approximately 20% of animal bites or scratches get infected in humans (5). Bacterial culturing from pet bite infections in humans is found to be smilar to the oral microbiota of the pets. Infections in dog bite wounds are usually dominated by aerobic bugs: P. multocida (50%), alpha-hemolytic Streptococcus (46%), Staphylococcus (46%), Neisseria (32%), and Corynebacterium (12%). However, following anaerobic bacteria are also isolated from infected wounds: Fusobacterium nucleatum (16%), Prevotella heparinolytica (14%), Propionibacterium acnes (14%), Prevotella intermedia (8%), and Peptostreptococcus anaerobius (8%) (22).
Normal human skin bacteria or other environmental microorganisms are scarcely isolated from infected wounds in bitten person (22–24). Usually, infection occurs within 8–24 h after the animal attack, with variable pain on the site of the injury. The cellulitis might be followed by discharge that contains pus, which can sometimes be foul-smelling. Immuno-suppressed patients with diabetes or liver dysfunction are frequently predisposed to develop serious infections after animal bites. In those cases, they may develop bacteremia faster and pass away in a shorter period of time (5). A penetrating bite close to the joints and bones may cause septic arthritis and osteomyelitis. Knowing the microbial composition of dental plaque biofilm formation in pets’ mouth is a key factor in wound chronicity in humans (5, 25).
Cat-scratch disease is a clinical syndrome that has been reported in people for over 100 years. Yet, the etiological agent Bartonella henselae, which was transmitted by cat scratches and bites, was only identified in 1992 (26). However, contact with cat saliva on broken skin or sclera can also cause Bartonellosis. A person who has had a cat scratch may show papules and pustules at the site of injury (the first initial sign). The disease may progress with a chronic non-healing wound, fever (sometimes), weak regional lymph circulation, and abscession. Cat owners and veterinarians are most at risk (27). Systematic medical treatment is usually needed in people with suppressed immune systems. Otherwise, encephalopathy, osteomyelitis, and granulomatous conjunctivitis might develop.
Horses and humans have always shared a close relationship due to recreation, sporting, and occupational reasons, for over thousands of years. In Europe, the number of horses per capita remained relatively stable during the past decade. Germany and Great Britain have the largest horse populations in the EU, whereas Sweden has the highest number of horses per capita. The frequency of infected horse bite wounds is estimated to be 3–5% in Europe (28, 29). However, it has been roughly estimated that the horse bites account for as high as 20% of overall animal bites in Turkey, which comes after dog bites (70%) (30). More extensive muscle damage may develop in most of the horse attacks, which is different from small animal bites. A mixture of aerobic and anaerobic organisms has been isolated from horse bites in humans, which are frequently dominated by Actinobacillus lignieresii (31, 32). Escherichia coli and Bacteroides species have also been isolated from foul-smelling infections and pus drainage after horse bites in humans (33).
Infectious diarrhea in companion animals is caused by Salmonella sp., Escherichia coli, Shigella sp., and Campylobacter sp. can also be transmitted to people through fecal oral route. It is difficult to estimate the distribution of these ubiquitous microorganisms. But it is known that they can be isolated from many healthy animals, which can be shed in their feces for long periods of time. Campylobacteriosis were the most frequently reported zoonotic bacterial diseases in 2009 among the EU member countries in humans (34). Like many other enteropathogens, they can cause gastroenteritis (diarrhea, vomiting), headaches, and depression, sometimes even leading to death. It is obvious that raw food diets for pets dramatically increase the risk of human exposure to such zoonotic bacterial enteropathogens, which cause gastrointestinal diseases.
Although pet birds, also called songbirds (e.g., canaries, finches, sparrows) and psittaciformes (e.g., parrots, parakeets, budgerigars, love birds) are a small fraction of adopted pets, they are widely popular in Europe and they are potential carriers of zoonotic diseases (35). Some of them could have an important impact on human health, such as chlamydophilosis (36), campylobacteriosis (37), and salmonellosis (38). Parrot fever (chlamydophilosis), which is caused by intracellular bacteria, Chlamydia psittaci, lives within the respiratory system of birds. Inhalation of dust, dander, and nasal secretions of infected birds is the main way of transmission to humans (39, 40). The mild to severe flu-like illnesses may develop and infected people might be misdiagnosed as influenza.
There is unfortunately a lack of quantitative research into the antimicrobial susceptibility of bacterial zoonotic organisms isolated from bite/scratch wounds or companion animal associated gastroenteritis. Zambori et al. (5) revealed an increased prevalence of drug resistance in animal bite isolates from people. Furthermore, methicillin-resistant Staphylococcus aureus (MRSA) or extended-spectrum beta-lactamases (ESBL) producing Enterobacteriaceae, which are known as nosocomial infections have been frequently isolated in companion animals (41), including horses (42). It might be one of the main reasons for the rising prevalence of these potential zoonotic pathogens in human clinical samples.
Zoonoses, or diseases of animal origin, are defined as diseases transmitted between animals and humans as a consequence of a direct contact, indirect environmental contact, or through food. Among recognised pathogens causing human diseases, almost 60% are of animal origin. They cause such diseases as toxoplasmosis, anthrax, rabies, Ebola haemorrhagic fever, severe acute respiratory syndrome (SARS), and primary HIV infection.
Already in 1906, doctor Silvio J. Bonansea described in his paper titled “Veterinary Hygiene Applied to the Protection of Man against Zoonoses” how animal health and hygiene are important for the production of safe and healthy meat and milk. Almost 50 years later, in November 1950 in Geneva, during the first meeting of the Expert Group on Zoonoses formed by the World Health Organisation (WHO) and the United Nations Food and Agriculture Organisation (FAO), a list of 86 diseases transmitted from animals to humans was identified. Twenty of those diseases were caused by bacteria. Nowadays, it is estimated that among 1400 pathogens causing human diseases, 800 are of animal origin.
There are numerous mechanisms of the transmission of zoonoses, and some diseases are transmitted in various ways, which significantly hinders the diagnostic process (Figure 1).
Symptoms of food poisoning may be variable, ranging from mild and transient, including nausea, vomiting, and malaise, to life-threatening kidney and liver failure, paralysis, and the dysfunction of the nervous system and brain. Cases caused by consumption of unsafe and contaminated food may also account for some instances of early death. Their global count may reach 4 million a year.
According to the WHO report published in 2015, almost 600 million cases of diseases caused by contaminated food were noted in 2010, including almost 350 million caused by pathogenic bacteria. Bacterial diseases of animal origin, e.g., caused by Campylobacter sp., Salmonella sp., Listeria sp., or the Enterobacteriaceae family, constitute a serious health risk both in developing countries and in advanced ones as well, such as EU countries and the United States. It is estimated that in the US, the number of food poisonings may reach as high as 48 million cases a year, with salmonellosis and campylobacteriosis alone affecting as many as 2 million people a year. In the EU, there are over 200,000 cases of bacterial zoonoses noted annually with presumably much higher numbers of real cases. According to the 2017 report of the European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC), the most common causes of food-borne zoonotic diseases were Campylobacter and Salmonella bacteria (Figure 2). In Canada, the annual incidence of food poisonings ranges between 3.1 and 5.0 million. In Australia, the incidence is 5.4 million.
Besides the health aspect, food poisonings also affect the economy due to the costs of hospitalisation, work absence, financial losses associated with consumers’ concerns of food quality, and the costs of legal proceedings. The U.S. Department of Agriculture (USDA) estimated that the country spends 10–83 billion USD a year on aspects associated with food poisonings. In Australia, the corresponding cost is over a billion USD a year, and in New Zealand, it is 86 million USD.
Through systematic evaluation of data reported in the scientific literature on zoonotic viruses, we identify several key virus characteristics and transmission mechanisms that are synergistic to zoonotic virus spillover, amplification by human-to-human transmission, and global spread. The majority (94%) of zoonotic viruses described to date (n = 162) are RNA viruses, which is 28 times higher (95% CI 13.9–62.5, exact P < 0.001) than the proportion of RNA viruses among all vertebrate viruses recognized, indicating that RNA viruses are far more likely to be zoonotic than DNA viruses, as has been reported among human pathogens6. Epidemiological circumstances involved in recent zoonotic transmission from animals to people are summarized here for 95 viruses with data on human activities enabling direct and indirect contact disease transmission and animal host taxa implicated in transmission. In general, wild animals were suggested as the source of zoonotic transmission for 91% (86/95) of zoonotic viruses compared to 34% (32/95) of viruses transmitted from domestic animals, and 25% (24/95) with transmission described from both wild and domestic animals (see Supplementary Table). Wild animals, which include a taxonomically diverse range of thousands of species, were significantly more likely to be a source for animal-to-human spillover of viruses than domesticated species (exact P = 0.001). Wild rodents were implicated as a source of spillover for 58% (55/95) of zoonotic viruses, particularly for zoonotic arenaviruses (n = 8/8, exact P = 0.019) and zoonotic bunyaviruses (n = 20/24, exact P = 0.004). Primates were implicated as a source of zoonotic retroviruses (exact P = 0.017), while bats were more implicated for zoonotic paramyxoviruses (exact P = 0.011) and most zoonotic rhabdoviruses (6/8, exact P = 0.002).
Emerging pathogens have been noted for their ability to infect a range of animal hosts578910. We find that most (63%) zoonotic viruses infecting humans were reported in animal hosts from at least two different taxonomic orders, and 45% were reported in four or more orders, in addition to humans. The virus-host unipartite network illustrates high connectivity among host groups sharing zoonotic viruses and the central role domestic animals play in cross-species transmission (Fig. 2). In a Poisson model predicting host range and evaluating common hosts and high-risk transmission interfaces, viruses with domestic animal hosts occurred in twice as many host orders than other viruses (Table 1). Most domestic animal groups clustered in the middle of the host network with high centrality measures and a high number of shared viruses (Fig. 2), indicating that domestic animals play a key role in cross-species transmission of zoonotic viruses. Among viruses from wildlife, we found higher host plasticity (ie, hosts from a higher number of taxonomic orders) in viruses transmitted at high-risk interfaces involving wild animals kept as pets, maintained in sanctuaries or zoos, and sold at markets, which were collapsed into one category due to similar effect and significance in the final Poisson model. We also found that vector-borne viruses were reported in three times the number of host taxonomic groups than non-vector-borne viruses, indicating that vector-borne pathogens have significantly broader host range than non-vector-borne viruses.
Based on data published to date, transmission of zoonotic viruses to humans occurs by direct or indirect contact with wildlife in a diverse array of interconnected animal-to-human interfaces, with little overlap with viruses transmitted primarily by vectors (Fig. 3). Zoonotic virus spillover from wildlife was most frequent in and around human dwellings and in agricultural fields, as well as at interfaces with occupational exposure to animals (hunters, laboratory workers, veterinarians, researchers, wildlife management, zoo and sanctuary staff). Primate hosts were most frequently cited as the source of viruses transmitted by direct contact during hunting (exact P = 0.051) and in laboratories (exact P = 0.009), while rodent hosts were more likely to be implicated in transmission by indirect contact in and around human dwellings (exact P < 0.001) and in agricultural fields (exact P = 0.001). Approximately 40% of zoonotic viruses involving wild animals required arthropod vectors for transmission to humans, with vectors providing an effective bridge for transmission of diseases from wild animals that do not normally contact humans. Zoonotic viruses with wild avian hosts were most likely to involve vectors (exact P < 0.001). Network analysis of disease transmission from wild animals illustrates that vector-borne viruses were the least connected to other transmission interfaces (Fig. 3), consistent with effective control of vector-borne diseases by elimination of vectors or contact with vectors. In contrast, 22% of viruses transmitted from domestic animals to humans were by vector only, with close proximity interactions with domestic animals enabling direct pathogen transmission to humans.
Once animal viruses have spilled over into humans, human-to-human transmission of zoonoses facilitates sustained spread of disease with a rapidity and reach infeasible for zoonotic viruses requiring contact with animal hosts for each transmission opportunity. Human-to-human transmissibility was described for 20% of zoonotic viruses investigated here (Supplementary Table). We find virus host plasticity to be positively correlated with capability for human-to-human transmission (Table 1). In a logistic regression model predicting virus capability for human-to-human transmission, we find viruses were significantly more likely to be human-to-human transmissible with each increase in virus host plasticity (count of host orders and ecological groups). Furthermore, we find viruses in the arenaviridae and filoviridae families to be more likely to possess human-to-human transmissibility, along with viruses transmitted by direct contact with hunted and consumed wildlife (Table 1). Hunting poses special risk for cross-species disease transmission of blood-borne zoonotic viruses1112 as evidenced by re-emerging threats, including ebolaviruses13 and primate retroviruses141516. Our findings therefore support speculation that hunting of high-risk host species carries an increased probability of spillover of zoonotic viruses that can be further spread by human-to-human transmission13.
We further characterized zoonotic virus capacity for spread by categorizing viruses according to geographic range in a single country (16%), >1 country in 1–3 World Health Organization-defined (WHO) regions (55%), or ≥4 WHO regions (29%), and used ordinal logistic regression to evaluate characteristics of viruses in broader range categories. We find viruses were more likely to be in broader geographic range categories with increasing host plasticity (Table 1). Among all high risk interfaces and hosts, only viruses transmitted to humans by contact with wild animals in the wildlife trade and in laboratories, such as lymphocytic choriomeningitis virus17, monkeypox virus18, herpes B virus19, and Marburg20, were more likely to have broader geographic reach.
Zoonoses are infections that can be transmitted from vertebrate animals to humans and vice versa (WHO 2018). Globally, zoonotic infections are responsible for a high disease burden; approximately 60% of all known human diseases and 75% of diseases associated with recent epidemics or pandemics were zoonoses (Woolhouse and Gowtage-Sequeria 2005; Taylor et al. 2009; WHO 2017). Despite the high prevalence of zoonoses, the emergence of zoonotic disease remains difficult to predict and the underlying mechanisms that drive these processes are not well-understood. Studies of zoonotic exposure and hazardous behavior, including the co-sampling of animals, humans, and food products with animal origins, are one approach for better predicting and ultimately intervening in zoonotic disease outbreaks. Contact with infected animals, and/or exposure to contaminated environments, contributes to the emergence and spread of zoonotic diseases in human populations. It is additionally known that increased contact between animals and humans provides more opportunity for exposure to zoonotic pathogens (WHO 2017). Accordingly, the human populations at the highest risk of zoonotic infections are those that have the most frequent interactions with animals. For this reason, slaughterers, animal health workers, animal-raising farmers, and those that trade in wildlife are likely at greater risk of zoonotic infection than those outside of the agricultural industry.
Southeast Asia is considered to be a major hotspot for emerging zoonotic diseases (Morse et al. 2012; Horby et al. 2013). Demography, behavior, attitudes, culture, large animal populations, a high diversity of wild mammalian species, and the coexistence of a broad spectrum of diseases in human and animals are distinctive features of this region, which may lead to the more frequent emergence of zoonotic disease (Morse et al. 2012; Horby et al. 2013; Morand et al. 2014). However, we have a poor understanding of the specific features that lead to zoonotic disease transmission, such as the behavior of those that have sustained contact with animals. Here, we aimed to assess human exposure to animal sources which may be potential reservoirs of zoonotic disease. Additionally, we aimed to investigate the demographics, attitudes, and behavior of assumed high-risk individuals (those with a sustained occupational exposure to animals) living in Vietnam, a country located within the Southeast Asian epicenter of zoonotic diseases. Therefore, we accessed data from a high-risk sentinel cohort (HRSC) study, which was a component of the VIZIONS (Vietnam Initiative on Zoonotic InfectIONS) program (Carrique-Mas et al. 2015; Rabaa et al. 2015) to assess how cohort members interacted with animals and identify potential disease exposure risks.
The burden of viral disease is a global concern. Due to their unique properties, viruses have a particular relevance when analyzing the interaction among humans, animals, and the environment. Viruses are small compared to other pathogens, facilitating transport in the environment. Moreover, their resistance to disinfection and ability to survive for prolonged periods in water and solids make their transmission from the environment to suitable hosts likely. This is compounded by their low infectious dose, inability to be treated by antibiotics, and their proclivity for adaptive mutation. Additionally, viruses do not replicate outside their host cells, therefore detection in environmental samples can be directly related to the human or animal population that excreted these viruses.
Fig. 1 summarizes viral exposure pathways and the relevance of the One-Health approach. One-Health is a relatively new approach to the solving of global health challenges. Formally put forth by the One Health Commission in 2007, the concept is defined as “the collaborative effort of multiple disciplines – working locally, nationally, and globally – to attain optimal health for people, animals and our environment.” Consequently, a key component to the One-Health approach is the notion that human health, animal health, and environmental health are all innately interrelated. The quality and well-being of one group can directly and indirectly impact the quality of the other two groups. By taking all three aspects of health into account, solutions can be generated that not only address the health problems of a specific group but mitigate the source of those problems as well.
Much of the current work using the One-Health approach is focused upon the exposure pathway between humans and animals, while the water-related exposure pathway has not been thoroughly investigated from a One-Health perspective. The purpose of this paper is to explore water-related exposure pathways as they relate to human, animal, and environmental health, to explore the possibility of surveillance of water and wastewater systems as means of identification of endemic disease and potential outbreaks at a population level, and to develop a framework with which to apply the One-Health methodology for early detection and management of water-related viral outbreaks.
Thousands of different microorganisms affect the health and safety of the world's populations of humans, animals, and plants. Infectious microorganisms include species of bacteria, viruses, fungi, and protozoa. Many different medical and governmental organizations have created lists of the pathogenic microorganisms most relevant to their missions. For example, the Centers for Disease Control and Prevention (CDC) maintains an ever-changing list of notifiable diseases, the National Institute of Allergy and Infectious Disease (NIAID) lists agents with potential for use in bioterrorist attacks, and the Department of Health and Human Services (HHS) maintains a list of critical human pathogens. Unfortunately, the nomenclature for biological agents on these lists and pathogens described in the literature is imprecise. Organisms are often referred to using common names, alternative spellings, or out-dated or alternative names. Sometimes a disease rather than a particular organism is mentioned, and often there may be multiple organisms or co-infections capable of causing a particular disease. Not surprisingly, this ambiguity poses a significant hurdle to communication among the diverse communities that must deal with epidemics or bioterrorist attacks.
To facilitate comprehensive access to information on disease-causing organisms and toxins, we have developed a database known as "The Microbial Rosetta Stone" that uses a new data model and novel computational tools to manage microbiological data. This article focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. It provides a compilation of lists, taken from the database, of important and/or regulated biological agents from a number of agencies including HHS, the United States Department of Agriculture (USDA), the CDC, the World Health Organization (WHO), the NIAID, and other sources. We curated these lists to include organism names that are consistent with the National Center for Biotechnology Information (NCBI) nomenclature and to provide sequence accession numbers for genomic sequencing projects (if available). Important synonyms or previously used names that identify the organisms are also shown. We have organized the lists according to phylogenetic structure. This paper provides graphic representations of the phylogenetic relatedness of important pathogenic organisms.
The goal of the database is to provide an informative, readily accessible, single location for basic information on a broad range of important disease causing agents. The database will help users to avoid the pitfalls of confusing nomenclature and taxonomic relationships and allow access to literature on in-depth studies. The database can be accessed at .
Campylobacteriosis is a zoonotic disease which has a worldwide public health impact and is caused mostly by Campylobacter jejuni or Campylobacter coli. Campylobacter is S-shaped, or curved rod-shaped bacteria of the epsilon class of Proteobacteria. Poultry are a natural reservoir and are frequently colonized with thermophilic Campylobacter species, primarily C. jejuni and C. coli. Although Campylobacter is insignificant for poultry health, it is a leading cause of foodborne gastroenteritis in humans worldwide. Contaminated poultry carcasses are recognized as the main source for human exposure. It is extremely difficult to keep poultry flocks free of Campylobacter which is commonly present in the poultry houses environment. During the slaughtering process, contamination of the carcasses with high numbers of Campylobacter is unavoidable.
The disease is endemic in Egypt and is a major cause for pediatric diarrhea. Nonetheless, the epidemiology in animals and humans has not been fully characterized. In the period from 2006 to 2015, several studies described the isolation of Campylobacter, mainly C. jejuni, in chickens, raw milk, milk products, diarrheic and normal camel calves and stool of diarrheic patients in several governorates in Egypt. Backyard poultry remains the main source of Campylobacter transmission to humans. In one governorate, Campylobacter spp. including C. jejuni and C. coli were isolated from 47.5% of chicken and 2.7% of human samples. Chickens and humans isolates were genetically similar signifying the high possibilities of zoonotic transmission from animals to humans. Isolation of Campylobacter from diarrheic children was more frequent (17.2%) than Salmonella (3%), Shigella (2%), or other bacterial pathogens (1%). In another governorate, 59 C. jejuni and/or C. coli isolates were recovered from diarrheic humans. The isolates belonged to 14 groups for flaA and 11 groups for flaB genes indicating considerable genetic variability among isolates belonging to the same serogroup.
Increasing morbidity from zoonoses is a significant problem in terms of global health, and they are currently considered exotic in Europe. Zoonoses are infectious or parasitic diseases transmitted by animals to humans (Spahr et al. 2018). These infections as aetiological factors can develop in humans in several ways:
by the digestive tract, where the microorganism gets into the body via infected feed (meat) or water, which is quite often in large-scale farming. Therefore, Escherichia and Salmonella transmission to people occurs mainly through ingestion or frequent contact with infected birds. The above microorganisms can live in the external environment for a long period of time without damage to the pathogenic properties.by skin laceration; a break in the continuity of the skin promotes infection by pathogens of the staphylococci and streptococci families. In addition, the infection is intensified by the release of toxins into the host system.by the respiratory system (by inhalation of dust in which the pathogens are raised); infection occurs through direct contact of a healthy individual with contaminated excretion or through indirect contact (low hygiene at the slaughterhouse) with contaminated faeces and secretion on bird feathers (Hugh-Jones and de Vos 2002).
Humans are more susceptible to zoonoses carried by mammals than birds, and they share more diseases with them. This sharing is due to a higher degree of similarity between the intracellular environment of mammals (to which they belong), rather than birds. Many microorganisms need proper conditions and parameters to determine their host, for example, the presence of its receptor on the surface of the cells. These receptors can serve as a site for attachment and penetration into cells, which provides a pathway for the development of infection. The above situation determines the susceptibility of one animal species to a pathogen and resistance of another species. Vectors, such as insects, are also involved in the transmission of various pathogens, which may have an effect on the immune system. In the case of infecting a human with an avian zoonosis, the course of the disease is usually severe with general life-threatening symptoms. People who have been infected with an avian zoonosis require in-hospital treatment in isolation. Avian zoonoses in humans may end in death or a chronic disease requiring prolonged administration of antibiotics (Hugh-Jones and de Vos 2002).
Hence, the aim of this work is to present the aetiological factors of bird zoonoses, which are currently the most threatening to the European population. In addition, the epidemiological and economic analysis of the above infections in humans is presented. In general, zoonoses from birds can be divided by the type of the infectious agent: bacterial, viral and fungal.
The 2009 A(H1N1)pdm09 influenza pandemic, the SARS epidemic in 2003, and the recent emergence of a novel coronavirus are recent reminders of the global health threat posed by zoonotic viruses. Prior to widespread emergence in human populations, such pathogens can cause occasional infections in sub-populations that have been exposed to reservoir species (common reservoir species include for example bats, birds, swine, non-human primates). Whilst viruses causing such “spill-over” infections are usually poorly adapted for sustained human-to-human transmission, they are under strong selection pressure to increase transmissibility once in humans. If the reproduction number R (i.e., the average number of persons infected by a case) evolves to exceed 1, a large scale epidemic in humans may result. Over the last decade, particular concerns were raised regarding highly pathogenic H5N1 avian influenza, due to the high mortality rate seen in humans and the virus's rapid spread in avian populations. However, as the A(H1N1)pdm09 influenza pandemic demonstrated, H5N1 is not the only influenza virus that may pose a pandemic risk. Recently, a swine-origin triple reassortant influenza A(H3N2) variant virus has emerged in the United States, carrying the matrix gene (M) from the H1N1pdm09 virus (H3N2v-M)–. Studies in animal models have suggested that the presence of the H1N1pdm09 M gene may increase transmissibility of the virus,. From January 2012 to September 2012, 307 laboratory-confirmed H3N2v-M human infections were reported to Centers for Disease Control and Prevention (CDC) as opposed to 12 throughout 2011. The majority of cases have been associated with agricultural fairs but there are documented events of human-to-human transmission. The surge in cases observed in summer 2012 raised public health concerns. Threats from zoonoses are not limited to influenza: more than half of all recent emerging infectious disease events were zoonotic.
For efficient prevention and control, quantitative and rigorous assessment of the risks associated with emerging zoonoses is desirable—in particular the risk that an emerging pathogen evolves to cause sustained human-to-human transmission. One approach to such risk assessment is by monitoring the reproduction number R of zoonoses in humans, with an alarm being raised if R increases or approaches 1–. However, until now, estimating R required detailed outbreak investigations of human clusters, and suffered from three important limitations: (1) the resources, access, and expertise needed to conduct investigations is not always available; (2) the proportion of cases that are missed during outbreak investigations may vary by setting and be difficult to assess; (3) even if the study is complete, the data collection process can be affected by a selection bias whereby larger outbreaks are more likely to be detected so that estimates of transmissibility may be biased upward. Consider for example a scenario where R = 0.7, where each case has the same detection probability ρ = 1%, and assume that once a cluster is detected, detailed outbreak investigation ensures that all cases in the cluster are detected. With an average size of 18.3 and a 21% probability of 1-case cluster, clusters that are detected are substantially larger than normal ones (average size: 3.3; 65% probability of 1-case cluster) (Figure 1A). As expected, this selection bias leads to R being overestimated as illustrated for methods that use the distribution of detected cluster sizes (Figure 1B).
Here, we present a new approach to estimate R during spillover events, aiming to address many of the limitations of existing methods. We apply our approach to assess the human-to-human transmissibility of swine-origin influenza A variant (H1N1v, H1N2v, and H3N2v) virus, in particular that of the H3N2v-M virus, from US surveillance data for the period December 2005–December 2011. We also present applications to another zoonotic virus (Nipah virus in Malaysia and Bangladesh) as well as to a non-zoonotic pathogen (Vibrio Cholerae in the Dominican Republic).
Poxviruses are double-stranded DNA viruses with large genomes (up to 300 kb) belonging to the family Poxviridae. The family is divided into the invertebrate-infecting entomopoxvirinae and chordate-infecting chordopoxvirinae. The latter subfamily is further divided into ten genera and contains many important infectious agents of both animals and humans. The now-eradicated Variola virus (VARV, the causative agent of smallpox) illustrates the potential consequences of poxvirus infections having arguably caused more deaths in human history than any other infectious agent. Aside from humans, chordopoxviruses are also found in a multitude of terrestrial, aquatic and arboreal animal species from diverse taxa e.g., crocodiles, sea lions, birds, camels, etc. and many poxviruses are capable of infecting multiple host species and cause cross-species (including zoonotic) infections. For example, monkeypox virus has been recognized as a zoonotic agent since the 1970s and is classed a bioterrorism agent. Further to human disease burdens, cross species infections of poxviruses between non-human species can also have devastating consequences e.g., the near-extinction of red squirrels in the UK after the introduction of squirrelpox with grey squirrels from the USA. Owing to the significance of these zoonotic and cross-species poxvirus infections, poxvirus host range is a key area of research.
Poxviruses exhibit a heterogeneous host range with some poxviruses having a very broad host range (e.g., cowpox infects rodents, dogs, cats, horses, cows, primates including humans), and others being very specific (e.g., VARV is a human only pathogen). Although some poxvirus genera are known to exhibit broad host tropisms (e.g., orthopoxviruses) and are consequently thought to manifest greater zoonotic risks, phylogenetic relatedness among viruses is not indicative of poxvirus host range. In fact, determinants of poxvirus host range are poorly understood and viral tropism is not typically restricted at the level of cellular entry. Due to highly conserved virion proteins, most poxviruses can enter a wide variety of host cell types, with restriction of infection occurring downstream of entry (either through a lack of host factors or through the innate immune system). Consequently, changes in poxvirus host range are typically determined by changes in virus genome complement (e.g., gene duplication/gain/loss) that allow for subversion of host restriction rather than point mutations, as is the case for some viruses e.g. parvovirus and influenza. Genes that are known to cause shifts in poxvirus host range generally have functions relating to the interplay of the host innate immune mechanisms with the virus. These genes are termed poxvirus host range genes and although approximately 15 have already been identified, more work is needed to fully understand their restriction mechanisms and to identify novel determinants of poxvirus host range.
Bats are an ancient, highly diverse order of mammals that are known to be reservoirs for a large number of viruses. “Bats” is the collective term for some approximately 1200 species of mammals thought to have diverged some 50 million years ago (mya; comparatively humans and great apes are thought to have diverged ~5 mya). Second only in diversity to rodents, bats are subdivided into two suborders, commonly called megabats and microbats, on the basis of behavioral and physiological traits as well as molecular evidence. There has been a recent increase in interest regarding the relationship of bats with viruses (Figure 1) as some species of bats are reservoir hosts for lethal viral zoonoses such as SARS coronaviruses, paramyxoviruses (e.g., Nipah and Hendra viruses), and filoviruses (e.g., Ebola and Marburg virus) and numerous lyssaviruses. Outbreaks of disease attributable to bat-related zoonoses have high economic and human costs and their discovery has resulted in concerted research effort to isolate and characterize viruses from bat populations. Consequently, large numbers of previously unknown viruses have since been identified in bat populations for which the zoonotic potential is unknown, including novel influenza types and hepadnaviruses. As a result, there has been well-grounded speculation that owing perhaps to physiological, ecological, evolutionary, and/or immunological reasons, bats may have a “special” relationship with viruses and be particularly good viral reservoirs with exaggerated viral richness. Indeed, a recent intensive study found that a single bat species likely carries ≥58 different viral species from only nine viral families. As well as the obvious first step of considering the zoonotic potential of newly identified bat viruses, further exploring the impacts of these findings and the opportunities they present for multiple research fields is necessary to capitalize on these discoveries.
Poxvirus infections have recently been identified in bats, comprising part of the increase in viral families newly identified in this taxonomic order. Here, we review the current evidence of poxvirus infections in bats, present the phylogenetic context of the viruses within the Poxviridae, and consider their zoonotic potential. Finally, we speculate on the possible consequences and potential research avenues opened following this marrying of a pathogen of great historical and contemporary importance with an ancient host that has an apparently peculiar relationship with viruses; a fascinating and likely fruitful meeting whose study will be facilitated by recent technological advances and a heightened interest in bat virology.
No other modern epidemic or pandemic mobilized the global health community to action like the 2013–2016 Ebola virus disease outbreak in western Africa. Following the outbreak, calls for pandemic-threat warning systems came from both traditional public health policy-makers1,2 and national governments.3 As currently conceptualized, the first step in the identification of a pandemic threat requires an outbreak of sufficient size to come to the attention of medical personnel who are sufficiently influential and persistent to ensure action.4 Once an outbreak is verified, well-established protocols for disease investigation and control can be swiftly put in place – although it may be many months before the main risk factors and most effective control measures are identified. The Ebola outbreak in western Africa probably began in December 20135 but it took another year before traditional burial practices were found to be a leading cause of the rapid spread of the causative virus.6
By the 1970s, the human burden of infectious diseases in the developed world was substantially diminished from historical levels, largely due to improved sanitation and the development of effective vaccines and antimicrobial drugs. The emergence of a series of novel diseases in the 1970s and 1980s (e.g. toxic shock syndrome, Legionnaire's disease), culminating with the global spread of HIV/AIDS, however, led to infectious disease rising back up the health policy and political agendas. Public concern about emerging infectious diseases (EIDs) has been heightened because of the perception that infectious diseases were previously under control, because of their often rapid spread (e.g. severe acute respiratory syndrome; SARS), because they often have high case fatality rates (e.g. Ebola virus disease) and because the development of drugs and vaccines to combat some of these (e.g. HIV/AIDS) has been slow and costly. By the 1990s, authors had begun to review similarities among these diseases and identify patterns in their origins and emergence. Similarities included a skew to zoonotic pathogens originating in wildlife in tropical regions (e.g. Ebola virus), and that emergence was associated with environmental or human behavioural change and human interaction with wildlife (e.g. HIV/AIDS) or with domestic animals which had interactions with wildlife (e.g. Nipah virus) [5–7]. Emergence was found to be exacerbated by increasing volumes and rates of human travel and globalized trade.
By the end of the 1990s, the study of EIDs was a staple of most schools of public health, a key focus of national health agencies, a book topic and the title of a scientific journal. Novel diseases continued to emerge, often from unexpected reservoirs and via new pathways. For example, between 1994 and 1998, three new zoonotic viruses (Hendra, Menangle and Nipah viruses) emerged from pteropodid bats in Australia and southeast Asia. Each of these was transmitted via livestock (horses or pigs), and each belonged to the Paramyxoviridae. Around this time, emerging diseases were identified in a series of well-reported die-offs in wildlife, including canine distemper in African lions (Panthera leo) in the Serengeti, chytridiomycosis in amphibians globally, pilchard herpesvirus disease in Australasia and West Nile virus in corvids and other birds in New York [10–13]. Pathogens were also implicated for the first time in species extinctions, or near-extinctions, e.g. canine distemper in the black-footed ferret (Mustela nigripes), chytridiomycosis in the sharp-snouted day frog (Taudactylus acutirostris) and steinhausiosis in the Polynesian tree snail, Partula turgida [14–16]. Novel diseases and their emergence in people and wildlife were reviewed, and commonalities in the underlying causes of emergence discussed, in a paper published at the end of the decade. Here, we re-examine some of the key conclusions of that paper, review how the field has progressed 17 years on and identify some of the remaining challenges to understanding and mitigating the impacts of disease emergence in and from wildlife.1
Each year in the United States, there are approximately 76 million cases of food-borne illness, including 325,000 hospitalizations and 5,000 deaths. In an estimated 2 to 3% of these cases, chronic sequelae develop. These sequelae include renal disease, cardiovascular diseases, gastrointestinal disorders, neural disorders, and autoimmune disease. The estimated cost of food-borne illness in the United States is $23 billion annually. Mishandling of food is believed to be responsible for 85% of all outbreaks of food-borne disease in developed nations, primarily due to a lack of education. Food-borne pathogens [see Additional File 3] are also important because they represent one of the largest sources of emerging antibiotic-resistant pathogens. This is due in part to the administration of sub-therapeutic doses of antibiotics to food-producing animals to enhance growth. For example, certain strains of Salmonella show resistance to eight or more antibiotics. Studies have shown that antibiotic resistance in Salmonella cannot be traced to antibiotic use in humans, suggesting that antibiotic use in animals is the primary cause of resistance.
While much is known about the major microbes responsible for diseases, there are still many undiagnosed cases of infectious disease. It has been estimated that as many as three-fifths of the deaths from acute gastroenteritis per year in the United States are caused by an infectious organism of unknown etiology. Four of the major causes of food-borne infections (Campylobacter jejuni, Escherichia coli O157:H7, Listeria monocytogenes, and Cyclospora cayetanensis, Figure 2) were only recently recognized as causes of food-borne illness.
Viruses can be identified by a wide range of techniques, which are mainly based on comparisons with known viruses. Historic methods include electron microscopy, cell culture, inoculation in suckling mice and serology, but these methods have limitations. For example, many viruses cannot be cultivated, excluding the use of cell line isolation and serologic techniques, and can only be characterized by molecular methods. In 2011, Bexfield summarized the different molecular techniques that identify new viruses such as microarray, subtractive hybridization-based and PCR-based methods. Although these techniques have allowed the discovery of many viruses, the prior knowledge of similar viruses is required. Recent advances in sequence-independent PCR-based methods have overcome this limitation, and Sequence-Independent Single Primer Amplification (SISPA), Degenerate Oligonucleotide Primed PCR (DOP-PCR), random PCR and Rolling Circle Amplification (RCA) methods have emerged. The end result of most of these PCR methods is amplified DNA that requires definitive identification by sequencing.
Novel DNA sequencing techniques, known as “Next-Generation Sequencing” (NGS) techniques, are new tools providing high-throughput sequence data with many possible applications in research and diagnostic settings. With the development of different NGS platforms, it is now possible to sequence all viral genomes in a given sample without previous knowledge about their nature with the use of sequence-independent amplification followed by high-throughput sequencing. This combination of techniques, known as viral metagenomics, allows the discovery of completely new viral species within a complex sample and, due to decreasing costs, are nowadays exponentially increasing.
NGS techniques are able to generate a huge number of sequences, ranging from thousands to millions of reads, in only one reaction. In order to fully benefit from this depth of sequencing to identify infectious agents present in a given environment, host DNA/RNA should previously be removed from samples. Preliminary treatments are therefore required prior to nucleic acid amplification and sequencing, mainly based on nucleases treatments and/or viral purification by ultracentrifugation on sucrose, cesium chloride or glycerol gradients. These strategies are known as “Particle-Associated nucleic acid amplification”, i.e., they try to isolate intact (i.e., infectious) viral particles from their environment, protected from the action of nucleases. Subsequent low amount of nucleic acids have required the use of Sequence-Independent Amplifications (SIA) such as SISPA, DOP-PCR, random PCR, RCA. Although these techniques allow generating enough nucleic acid material for sequencing, their main disadvantage remains that they distort quantitative analyzes by introducing bias of amplification in viral diversity studies. As a consequence, quantitative analyses of the composition of resulting viromes may not reflect the reality.
In diagnostic virology, in either human or veterinary medicine, viral metagenomics has allowed the discovery of causative viral agents of disease conditions. Virome analyses have also been conducted to describe the baseline viral diversity in healthy human conditions, as a prior knowledge before studying the viral flora of pathologic conditions.
In the same way, the use of viral metagenomics as a tool for arboviral and zoonotic disease surveillance requires prior knowledge of the viral diversity associated to hematophagous arthropods and animals in close contact with humans. This review thus summarizes our current knowledge of the diversity of viral communities associated with several arthropods, wildlife and domestic animals and present its potential applications for the surveillance of zoonotic and arboviral diseases.
Wildlife markets occur in several regions of the world and take different forms. According to region, these markets offer animals for various reasons including culinary, medicinal and pet purposes. In this article we focus on visitor behaviour and public health implications associated with the display and sale of amphibians and reptiles at exotic pet markets in the UK and elsewhere in the European Union (EU).
Human health is reportedly a key concern at pet markets due to the attendance of the public, and because many animals are likely to harbour transmissible zoonotic pathogens.1,2 Zoonotic diseases are pathogenic infections and infestations transmissible from animals to humans. There are around 200 zoonoses3 and approximately 40 of these are associated with amphibians and reptiles (for examples, see Appendices A and B). Captive reptiles are routinely identified as reservoirs of infectious bacteria, for example, Salmonella,4 and all reptiles should be presumed to harbour Salmonella.1,5–8
In 2009, a case-control study in the UK indicated that reptile keepers were nearly 17 times more likely to get sick than those who had no contact with these animals.9 A limited study of seven door handles at a major pet market in Germany in 2010 revealed the presence of two distinct species of Salmonella, S. ramatgan and S. subspecies V (N Kutscher, personal communication, 2011), both of which are reptile-associated.
More generally, a survey of 1410 human diseases found 61% to be of potentially zoonotic origin.10 Also, 75% of global emerging human diseases are zoonotic.11
It is believed that epidemics such as SARS (severe acute respiratory syndrome), monkey-pox and avian influenza H5N1 may have emerged from wildlife markets.1,5,8,11 The arbitrary mixing of a wide variety of species that would not normally meet together in conditions of highly questionable animal husbandry and public health protection measures, raises multifactorial concerns about these markets and their implications for public health.1,5,8,12,13 Many cases of zoonotic disease are, however, probably misdiagnosed as other conditions and under-reporting in general is a likely major factor in under-ascertainment of cases.2 Certain common zoonoses symptomatically superficially resemble common illnesses such as gastrointestinal, respiratory, influenzal and dermatological disorders and disease. General medical practitioners who are unfamiliar with zoonoses do not typically enquire of patients about direct or indirect contact with an exotic animal.2
Significant zoonotic episodes arise from indirect contact with an animal. Indirect pathogen contamination and dissemination involving reptiles and intermediary surfaces, for example, door handles, clothes, table tops, walls, household utensils and shaking of hands, has been reported as an important factor in transmission.7,14,15 One notable example involved over 300 public attendees to a zoo who acquired Salmonella infection via a wooden stand-off barrier around a lizard enclosure and despite having had no actual contact with the reptiles.16
The presumed primary transmission route for many amphibian- and reptile-borne potential pathogens is via faecal–oral ingestion.17 However, human skin scratches from the claws of lizards,18 and bites from snakes and lizards also may transmit contaminants.14,18 Also, direct contact between any contaminated reptile and open human lesions, such as sores, or via reptile debris penetrating human orbital or aural sites, are further potential routes of infection.14 Aquatic turtles and other species of water-dwelling reptiles may contaminate large bodies of water – resulting in contaminated splashes, droplets and smears that may lead to human infection. Lizards are handled more than turtles and are more likely to introduce infection via skin scratches. Snakes are handled far more frequently than even lizards and thus may spread contaminants more widely and consistently. Diverse surfaces may act as intermediary carriers of many biotic contaminants and once a surface is contaminated, potential contagions may long persist.19
Hand washing and the use of disinfectant gels and sprays are commonly recommended and perceived as sufficient hygiene measures to eradicate Salmonella and any other potential pathogens.14,15 However, these hygiene methods, as generally practiced, do not provide reliable protection against diverse amphibian- and reptile-borne contaminants.14,15 Indeed, the use of these materials and methods may generate undue over-reliance and misplaced confidence in personal disease prevention and control that may lead to infection as a result of complacency.20
The aim of this investigation was to assess public behaviour in the context of potential contamination threats at close-quarters in a probable zoonotic pathogen rich environment. We conducted on-site assessments at three key European pet market events: Terraristika (Hamm, Germany), the IHS Show (Doncaster, UK) and Expoterraria (Sabadell, Spain) during 2011. Each event involves a substantial number of stalls that collectively sell thousands of exotic animals directly to the public. Several hundred such events occur annually throughout Europe.21
The Campylobacteriaceae family is divided into four genera: Campylobacter, Arcobacter, Dehalospirilum, and Sulfurospirilum. Campylobacter spp. are small (0.2–0.9 μm wide and 0.2–5.0 μm long), spirally curved, Gram-negative rods that do not form spores. They move in a way that resembles a corkscrew. This movement is possible due to a single, polar flagellum positioned on one or both ends of the cell. Thirty-two species and 13 subspecies of those bacteria were identified. As pathogens, the greatest role is played by Campylobacter jejuni subs. jejuni (95% of cases of zoonoses) and Campylobacter coli (5% of infections). They differ from other pathogenic bacteria transmitted by food as they have the ability to grow in an atmosphere containing nearly 10% of CO2 and 5% of O2 (microaerophils) at a narrow range of temperatures ranging from 30 to 46 °C (the optimum growth temperature is 40–42 °C), which makes them thermophilic. Growth of those microbes is not observed at water activity (aw) below 0.987, while the optimum value is 0.997. In conditions that do not favour growth, those bacteria are able to form viable but nonculturable cells (VBNC). Moreover, Campylobacter jejuni may survive for more than 4 h at 27 °C, which prevents these bacteria from multiplying outside animal hosts or in food during storage. The other feature that allows survival of Campylobacter spp. in unfavourable conditions is their ability to form a biofilm on abiotic surfaces, which ensures a supply of nutrients and mechanical protection even though they cannot grow.
Already in 1909, bacteria belonging to genus Campylobacter were a known cause of animal diseases, but only as late as in 1980 the discovery was made that they also cause health problems in humans. The incidence of infections caused by Campylobacter spp. has been constantly growing. Currently it is the most common foodborne bacterial zoonosis in the world. It is estimated that Campylobacter spp. cause 500 million infections in the world every year. In the European Union, the number of cases of campylobacteriosis has been the highest of all zoonoses since 2005, with the number of confirmed cases of infection that year being 197,363. After 2010, the number of people diagnosed with this disease has been over 200 thousand a year. In 2012, the EFSA noted 214,268 cases, and in 2015, the number of noted infections rose to 229,213, reaching 246,307 in 2016. It is estimated that in the United States, campylobacteriosis affects a million people a year, and in Canada, there are over 200 thousand cases registered each year. Cases of campylobacteriosis have become common also in Africa, Asia, and the Middle East, particularly in children.
Sequencing of the C. jejuni NCTC 11168 genome demonstrated the existence of genes that code some proteins with infectious potential. Despite numerous studies on the molecular genetics of Campylobacter spp., their mechanisms of pathogenicity and virulence remain poorly understood. Although the bacteria are considered to be susceptible to stress associated with environmental conditions, in the course of evolution, they were able to develop some complex mechanisms of survival and virulence, as presented in Table 1.
In 1981, British doctor of medicine David A. Robinson determined that the human infective dose of Campylobacter jejuni is at the level of 500 to 800 microorganisms. The dose was later confirmed in other studies. In 1988, doctor Robert E. Black and colleagues carried out a study on 111 adult volunteers in Baltimore. The subjects were administered 150 mL of pasteurised milk inoculated with two different strains of Campylobacter jejuni isolated during the outbreak of campylobacteriosis in Connecticut and Minnesota. The infective dose ranged between 8 × 102 and 2 × 109 bacteria. After administration, volunteers were followed up by physicians for 12 days, and samples of stool were collected during that period. The study confirmed that a low infective dose such as 800 Campylobacter bacteria is sufficient to cause the disease, and the risk of infection increased with increasing inoculum. However, the severity of symptoms was not dependent on the bacterial count. There are also claims that 360 colony-forming units (CFU) of Campylobacter spp. could cause symptoms associated with campylobacteriosis, and 9 × 104 bacteria is considered the optimum infective dose. The disease incubation time usually ranges between 1 to 7 days before the development of symptoms and is longer in the case of individuals exposed to a lower infective dose. Symptoms accompanying the infection range from watery diarrhea to bloody stool, with fever, abdominal pain, vomiting, and dehydration. Symptoms disappear within 5–7 days. In developed countries, the course of the disease is usually more severe compared with developing countries. Moreover, campylobacteriosis may be associated with complications occurring in 1% of cases. Possible complications include: peripheral neuropathies, including the Guillain–Barré Syndrome (GBS, neurological disorder characterised by weakness of limbs, possible involvement of respiratory muscles, anaemia, and sensory loss); reactive arthritis (REA, involving knees and ankles, occurring about a month after infection and developing for as long as 5 years); and functional intestinal disorders, including irritable bowel syndrome (IBS).
Campylobacteriosis is most often caused by the consumption of contaminated poultry, beef, or pork (Figure 3). It was determined that nearly 30% of all cases of infection were caused by the consumption of poultry, including 50–80% of isolated Campylobacter spp. strains of chicken origin, 20–30% of cases caused by pathogens from cattle, and a low percentage of pathogenic strains originating from other sources, including game. Pathogenic bacteria which belong to Campylobacter genus do not proliferate outside the alimentary tract of warm-blooded animals but may survive as long as several weeks in food products, especially those stored at low temperatures.
Poultry consists of broilers, hens, turkeys, ducks, and ostriches, of which the meat industry uses mostly broiler chickens (Gallus gallus). Campylobacter spp. colonise the mucosa of the caecum and cloaca crypts of infected chickens, but may also be present in the spleen, blood, and liver. The bacterial count per 1 gram of chicken faeces may reach the level of 1010, causing no infection and leading to no changes in caecal mucosa. In newborn chickens before 3rd week of life, no presence of Campylobacter is found, which may be associated with the presence of antibodies from the maternal organism, the addition of antibiotics in feed, and development of the intestine and its microbiota. After that time, if a single bird in the flock contracts the infection, it will be transmitted to the rest within days (approximately 3 days) through pathogen-containing faeces, or by rodents, water, insects, or farm workers. It is estimated that in the EU, the amount of chicken meat available in retail markets containing Campylobacter spp. ranges between 60% and 80%, whereas in United States the amount is up to 98%.
Ruminants, including cattle, sheep, and goats, also act as a reservoir for Campylobacter bacteria. The alimentary tract of cattle is colonised by Campylobacter spp. mostly in the gut (duodenum, jejunum, small and large intestines), rather than in the rumen. It is estimated that these bacteria are present in approximately 80% of animals in an infected herd. The bacteria are less easily transmitted among sheep. The ratio of infected animals in a herd is estimated at 20%. Although there are no studies on Campylobacter infections in small ruminants, there are some data regarding pathogens isolated from sheep carcasses and from lamb available in retail markets, as well from the liver, gallbladder, intestinal content, and faeces. In the case of ruminants, the presence of Campylobacter bacteria in their alimentary tract is usually asymptomatic but may account for miscarriages in cows and sheep. Besides the intestine, Campylobacter spp. may be present on the surface of hooves, in bristles, or in lymphatic nodes. Not only meat products may be a threat but also dairy. Raw milk is most often cross-infected with Campylobacter spp. during milking or as a result of udder infection. Despite that broad spectrum of food products obtained from that group of animals, the most common source of infection transferred from ruminants is the environment, namely surface water, soil, air, pets (particularly cats and dogs), wild animals, and livestock serving as infection vectors.
Campylobacter spp. also inhabit the alimentary tract of 38–63% of pigs, but infections resulting from the consumption of pork are rare (0.4% of all confirmed cases of campylobacteriosis. Pigs are considered to be the main reservoir of Campylobacter coli (90% of strains isolated from pigs), contrary to other reported groups of animals that are mostly infected by Campylobacter jejuni. Pathogenic Campylobacter coli demonstrate a higher resistance to commonly used antibiotics, such as macrolides or quinolons, compared to Campylobacter jejuni. On the other hand, the species is not resistant to freezing and drying. For that reason, despite a high ratio of C. coli infected pigs in slaughterhouses, the pathogen is rarely isolated from porcine carcasses. Campylobacter genus bacteria are isolated from various porcine products, including hamburgers, roasted pork, and sausage. The source of campylobacteriosis may also be bone pork (e.g., loin) and offal (the liver, heart, kidneys, and guts).
Not only animals and food products of animal origin constitute a source of campylobacteriosis, but vegetables are also a frequent vector of transmission. Contamination of vegetables may be the result of direct or indirect contact with livestock faeces. Campylobacter spp. isolated from vegetables and fruit may remain on their surface for 1 to as many as 8 days. Infection is rarely primary (in the field, as a result of fertilizing with slurry or use of contaminated irrigation water) but often secondary—in kitchens (both home and commercial). In order to ensure appropriate hygienic conditions, vegetables have to be carefully washed before being peeled.
Many factors that can influence the transmission of infectious diseases are changing rapidly over time and this results in new patterns of disease emergence and spread. More specifically, in the last few decades, the emergences of several zoonoses such as avian influenza (AI) H5N1 or H7N9, the middle east respiratory syndrome (MERS) in the Arabic peninsula, Q-fever in the Netherland or Ebola in Western Africa have each time been considered as unprecedented events. We understand some of the reasons for these emergence events retrospectively, but we fail to predict them adequately. These emergences of zoonoses are of particular human health concerns. They caused several hundred human infections with high fatality rates and AI and MERS, for example, could gain the capacity to transmit between humans, and to cause epidemics of unknown magnitude and impact. We argue that the failure to predict these emergences may be due to two main reasons. First, predictions are most often based on what is currently known of a disease and its risk factors where it circulates, but we fail to consider factors that could be important in different areas or under different conditions. Second, gradual changes in anthropogenic, environmental and wildlife factors are difficult to monitor, and the result of their potential interactions through different conditional feedback loops are inherently difficult to predict. Recognizing these challenges, the FAO publication “World Livestock 2013: changing disease landscapes” proposed to structure the understanding and mitigation of emerging zoonoses by considering the pressure, state and response framework used in environmental sciences. The description and understanding of pressures is somewhat larger than the classical focus on risk factors, as it entails looking at broad-scale spatio-temporal pattern of changes in generic anthropogenic, environmental and wildlife drivers of change. For example, the description of changes in animal trade networks in response to new socio-economic conditions may influence a broader set of diseases that can transmit through those trade networks. Similarly, political and socio-economic instability and migration crises have disruptive implications for many human and animal diseases alongside other environmental and wildlife factors. Studying the state strives to understand how changes in pressures have resulted in disease outcomes, or may influence disease outcome in the future. It is disease-specific and aims towards a fine understanding of the mechanisms by which changes in those anthropogenic, environmental and wildlife drivers may influence the emergence, spread or persistence of a particular disease. Finally, the response looks at the different options of intervention at the pressure or state level to prevent emerging zoonoses or to mitigate their impact. In this paper, we discuss different sets of pressures that can be linked to emerging zoonoses, taking avian influenza as an example. Pressures typically include anthropogenic (trade of live animals and animal products, distribution of farms and livestock, farming practices, farmers’ behavior, product price and farmer’s income, hunting practices, game animal transport, short-term mobility and migration of populations, socio-economic instabilities, state of veterinary services, regulation), environmental (climatic variables, land-use, land-cover, habitat connectivity) and wild-host related drivers (wildlife or vector distribution and population dynamics, vector capacity, reservoir capacity).