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Infectious disease can be viewed as a play involving at least two characters: the pathogen and the host. While both roles can be represented by a great variety of performers, pathogens exhibit by far the highest variety and complexity. This review is about viral infections in animals. It aims first to give an idea of the enormous complexity and diversity of the existing infectious agents, emphasizing their extraordinary capacity for change and adaptation, which eventually leads to the emergence of new infectious diseases. Secondly, it focuses on the influence of the environment in this process, and on how environmental (including climate) changes occurring in recent times, have precise effects on the emergence and evolution of infectious diseases, some of which will be illustrated with specific examples. Finally, it describes the recent and dramatic expansion of two of the most important emerging animal viral diseases at present, bluetongue (BT) and West Nile fever/encephalitis (WNF), dealing with their relationship to climate and other environmental changes, particularly those linked to human activities, collectively known as “global change,” and that can be at least in part seen a consequence of the “globalization” phenomenon.
Amongst pathogens, RNA viruses were a major source of emerging diseases during the last 30 years. High mutation rate and in case of segmented genome, reassortment are responsible for genetic adaptability and variability of these viruses.
Two pathogens affecting cattle and sheep were responsible for major outbreaks in Mainland Europe in the past 15 years: Bluetongue virus (BTV) and Schmallenberg virus (SBV). These outbreaks were singular in several ways: the diseases were previously either never reported in such northern locations (bluetongue virus) or recently discovered (Schmallenberg virus); their emergence still has unexplained aspects; both viruses displayed the ability to cross the placental barrier. Moreover, these events confirmed that palearctic endemic Culicoides species contribute to the spread of BTV and SBV and to the epizootic aspect of the diseases.
Bluetongue virus causes the eponymous bluetongue disease (BT). BTV belongs to the family Reoviridae, subfamily Sedoreovirinae, and represents the type specie of the Orbivirus genus. The family Reoviridae currently contains fifteen genera of multi-segmented dsRNA viruses, including pathogens of a wide range of vertebrates (including humans), arthropods, plants, and fungi. Unlike the other reoviruses, all orbiviruses are arthropod-borne viruses (arboviruses). This genus currently contains 22 species as well as 10 unclassified “orbiviruses”.
Until recent nomenclature changes implemented by the International Committee on Taxonomy of Viruses Schmallenberg virus was part of the Bunyaviridae family, genus Orthobunyavirus, grouped within the serogroup Simbu along with at least 27 other virus species. The members of the Simbu serogroup show cross-reactions to the complement fixation test but are distinguished by seroneutralization and by genetic sequence analysis. Yet still part of the Orthobunyavirus genus, SBV, AKAV and Aino virus (AINOV) are now considered exemplar viruses of the species Sathuperi orthobunyavirus, Akabane orthobunyavirus, and Shuni orthobunyavirus, respectively. These belong to the new order Bunyavirales, family Peribunyaviridae (formerly Bunyaviridae), which comprises the genus Orthobunyavirus and Herbevirus (host range limited to insects).
Despite their belonging to different viral families, BTV and SBV have several features in common. These converging aspects warrant the present work discussing more specifically the elements to consider while designing experimental infections targeting ruminant host species. A particular emphasis will be given to placental crossing and teratogenic potential of these two viruses.
Canine morbillivirus (canine distemper virus, CDV) causes canine distemper (CD) in a wide range of mammalian hosts, and may produce systemic, respiratory, cutaneous, bone, and/or neurological manifestations in these animals1,2. CDV produces immunosuppression3 in susceptible hosts by targeting cells that express the signalling activation molecule (SLAM)4, which frequently results in opportunistic infectious diseases caused by agents such as Bordetella bronchiseptica5,6, Candida sp.7, Clostridium piliforme8, Toxoplasma gondii9–11, Dirofilaria immitis11, Mycoplasma cynos12, and Talaromyces marneffei13. Although the occurrence of CD is significantly reduced in domestic dog populations in developed countries due to the use of vaccination14, the disease is endemic and a major cause of canine mortality in urban populations of Brazil15,16, where an estimated 147.5–160.3 million USD is spent annually due to the therapy of the systemic effects of CDV15.
CDV has been diagnosed concomitantly with traditional viral infectious disease agents such as canine parvovirus-2 (CPV-2)17,18, canid alphaherpesvirus-118,19, canine adenovirus-1 and -2 (CAdV-1)20, and (CAdV-2)18,21 in dogs. Moreover, recently CDV has been identified in dogs simultaneously with emerging viral infectious agents including Canine kobuvirus22, Canine pneumovirus23, and Canine respiratory coronavirus6,23. Additionally, studies have detected canine infectious disease agents due to the amplification of nucleic acids in symptomatic6,23–25 and asymptomatic19 dogs by molecular assays. Alternatively studies have combined the pattern of organ disease observed by histopathology with electron microscopy20, immunohistochemistry (IHC)8,12,21,22,25,26 and/or the molecular identification8,10,12,18,22,27 of infectious disease agents of dogs.
Previous studies by our group8,10,18 and others12,21,26,27 have demonstrated the concomitant participation of several infectious disease agents in the development of diseases in dogs, principally puppies. It is proposed that puppies are probably more frequently coinfected by several infections disease agents than has been previously reported, particularly if there is the simultaneous involvement of CDV, and coinfections may result in the death of the affected dog due to multiple organ failure10. The objectives of this retrospective study were to evaluate the frequency of concomitant traditional infectious disease agents in the development of infectious diseases in puppies, correlate the presence of these pathogens with histopathologic patterns, and review specific aspects of the pathogenesis involving these infectious disease agents.
To illustrate the enormous complexity of animal viruses, consider the following example: take any animal species, e.g., bovine. There are five known species of herpesviruses that could infect bovines specifically. Similarly, there are nine different known equine herpesviruses, eight human herpesviruses, and so on and so forth (Pellet and Roizman, 2007). Bearing in mind that there are approximately 5,400 different species of mammals (Wilson and Reeder, 2005) and that most of them have yielded at least one, most frequently several distinct herpesviruses on examination, the number of existing mammalian herpesvirus species would be huge, probably in the range of thousands. But there are also herpesviruses specific for birds, for reptiles, for amphibians, etc., so the above number would be increased consequently with the number of other vertebrate species (for the moment viruses of invertebrates, a world largely to be discovered, will not be considered). Likewise, let’s bear in mind that there are other taxonomic families of viruses besides the Herpesviridae family, like the Poxviridae (e.g., smallpox and myxomatosis), Flaviviridae (e.g., yellow fever and dengue), Orthomyxoviridae (e.g., influenza), Picornaviridae (e.g., foot-and-mouth disease, polio, and hepatitis A), Reoviridae (e.g., BT and African horse sickness), etc., and for each family of viruses one can reason about in the same way. In light of this example, a first conclusion is that we only know a fraction of the viral pathogens that actually exist. To these, we must add the non-pathogenic viruses that circulate silently, which obviously are less known, and which probably exist in far greater numbers and variety than their pathogenic counterparts. The complexity of viruses of plants, bacteria, fungi, and parasites is not lower than that of animal viruses. This gives a rough idea of the real complexity of the virus world in which only a small part is known.
There was no difference in the gender (females, 7; males, 8) of the puppies during this study. Pure breed dogs (73.3%; 11/15) were predominant (Table 1) relative to their mixed breed counterparts (26.7%; 4/15). However, when the head conformation was considered within the purebred dogs28,29, most (54.5%; 6/11) were mesocephalic (medium-headed), followed by the brachycephalic (short-headed) breeds of dogs (36.4%; 4/11), and only one (9.1%) dolichocephalic dog. Additionally, most (72.7%; 8/11) of these were representatives of toy breeds, with only three large breed dogs. Furthermore, most (n = 5) of the cases occurred in 2013, followed by 2014 (n = 3), 2015 (n = 3), and 2017 (n = 3), with only one in 2016.
The principal clinical manifestations described are resumed in Table 1. Bloody diarrhoea (n = 11) was the most frequently described clinical manifestation, followed by anorexia (n = 5), abdominal pain (n = 4), and convulsions (n = 3). One puppy died (#12) without presenting any reported clinical manifestation. The course of clinical manifestations was acute in all puppies, varied between 1–10 days, and resulted in the spontaneous death of all puppies. The immunization history of these puppies was not known.
Depending upon the involvement of etiological agent, the infectious respiratory diseases of small ruminants can be categorized as follows [9, 14]:bacterial: Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, enzootic pneumonia, and caseous lymphadenitis,viral: PPR, parainfluenza, caprine arthritis encephalitis virus, and bluetongue,fungal: fungal pneumonia,parasitic: nasal myiasis and verminous pneumonia,others: enzootic nasal tumors and ovine pulmonary adenomatosis (Jaagsiekte).
Manytimes due to environmental stress, immunosuppression, and deficient managemental practices, secondary invaders more severely affect the diseased individuals; moreover, mixed infections with multiple aetiology are also common phenomena [5, 8, 13, 15].
These conditions involve respiratory tract as primary target and lesions remain confined to either upper or lower respiratory tract [7, 16]. Thus, these diseases can be grouped as follows [5, 8, 14, 17].Diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, mainly remain confined to sinus, nostrils, and nasal cavity. Various tumors like nasal polyps (adenopapillomas), squamous cell carcinomas, adenocarcinomas, lymphosarcomas, and adenomas are common in upper respiratory tracts of sheep and goats. However, the incidence rate is very low and only sporadic cases are reported.Diseases of lower respiratory tract, namely, PPR, parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others which involve lungs and lesions, are observed in alveoli and bronchioles.
Depending upon the severity of the diseases and physical status of the infected animals, high morbidity and mortality can be recorded in animals of all age groups. These diseases alone or in combination with other associated conditions may have acute or chronic onset and are a significant cause of losses to the sheep industry [3, 10]. Thus, the respiratory diseases can also be classified on the basis of onset and duration of disease as mentioned below [3, 9, 14, 18]:acute: bluetongue, PPR, Pasteurellosis, and parainfluenza,chronic: mycoplasmosis, verminous pneumonia, nasal myiasis, and enzootic nasal tumors,progressive: Ovine progressive pneumonia, caprine arthritis encephalitis virus, caseous lymphadenitis, and pulmonary adenomatosis.
Since the beginning of modern virology in the 1950s, transmission electron microscopy (TEM) has been one of the most important and widely used techniques for the identification and characterization of new viruses. Two TEM techniques are usually used for this purpose: negative staining on an electron microscopic grid coated with a support film and (ultra) thin section TEM of infected cells, fixed, pelleted, dehydrated, and embedded in epoxy plastic. Negative staining can be conducted on highly concentrated suspensions of purified virus or cell culture supernatants. For some viruses, TEM can be conducted on contents of skin lesions (e.g., poxviruses and herpesviruses) or concentrated stool material (rotaviruses and noroviruses). For successful detection of viruses in ultrathin sections of infected cells, at least 70% of cells must be infected, and so either high multiplicity of infection (MOI) or rapid virus multiplication is required.
Viruses can be differentiated by their specific morphology (ultrastructure): shape, size, intracellular location or, for some viruses, from the ultrastructural cytopathology and specific structures forming in the host cell during virus replication. Usually, ultrastructural characteristics are sufficient for the identification of a virus at the level of a family. In certain cases, confirmation can be obtained by immuno-EM performed either on virus suspension before negative staining or on ultrathin sections. This requires virus-specific primary antibodies, which might be not available in the case of a novel virus. For on-section immuno-EM, OsO4 post-fixation must be omitted and the partially dehydrated sample must be embedded in a water-miscible acrylic plastic (usually LR White). The ultrastructure of most common viruses is well documented in good atlases and book chapters and many classical publications of the 1960s, 1970s, and 1980s. Several excellent reviews were recently published on the use of TEM in the detection and identification of viruses.
Small ruminants particularly sheep and goats contribute significantly to the economy of farmers in Mediterranean as well as African and Southeast Asian countries. These small ruminants are valuable assets because of their significant contribution to meat, milk, and wool production, and potential to replicate and grow rapidly. The great Indian leader and freedom fighter M. K. Gandhi “father of the nation” designated goats as “poor man's cow,” emphasizing the importance of small ruminants in poor countries. In India, sheep and goats play a vital role in the economy of poor, deprived, backward classes, and landless labours. To make this small ruminant based economy viable and sustainable, development of techniques for early and accurate diagnosis holds prime importance. Respiratory diseases of small ruminants are multifactorial and there are multiple etiological agents responsible for the respiratory disease complex. Out of them, bacterial diseases have drawn attention due to variable clinical manifestations, severity of diseases, and reemergence of strains resistant to a number of chemotherapeutic agents. However, sheep and goat suffer from numerous viral diseases, namely, foot-and-mouth disease, bluetongue disease, maedi-visna, orf, Tick-borne encephalomyelitis, peste des petits ruminants, sheep pox, and goat pox, as well as bacterial diseases, namely, blackleg, foot rot, caprine pleuropneumonia, contagious bovine pleuropneumonia, Pasteurellosis, mycoplasmosis, streptococcal infections, chlamydiosis, haemophilosis, Johne's disease, listeriosis, and fleece rot [3–10].
The respiratory diseases represent 5.6 per cent of all these diseases in small ruminants. Small ruminants are especially sensitive to respiratory infections, namely, viruses, bacteria, and fungi, mostly as a result of deficient management practices that make these animals more susceptible to infectious agents. The tendency of these animals to huddle and group rearing practices further predispose small ruminants to infectious and contagious diseases [6, 9]. In both sheep and goat flocks, respiratory diseases may be encountered affecting individuals or groups, resulting in poor live weight gain and high rate of mortality. This causes considerable financial losses to shepherds and goat keepers in the form of decreased meat, milk, and wool production along with reduced number of offspring. Adverse weather conditions leading to stress often contribute to onset and progression of such diseases. The condition becomes adverse when bacterial as well as viral infections are combined particularly under adverse weather conditions. Moreover, under stress, immunocompromised, pregnant, lactating, and older animals easily fall prey to respiratory habitats, namely, Streptococcus pneumoniae, Mannheimia haemolytica, Bordetella parapertussis, Mycoplasma species, Arcanobacterium pyogenes, and Pasteurella species [2, 4, 7–9, 12, 13]. Such infections pose a major obstacle to the intensive rearing of sheep and goat and diseases like PPR, bluetongue, and ovine pulmonary adenomatosis (Jaagsiekte) adversely affect international trade [2, 9, 10, 13], ultimately hampering the economy.
Viruses are obligate intracellular pathogens that require host cells in order to replicate and produce infectious progeny. Virus entry into host cells is followed by capsid uncoating, genome transcription and replication, synthesis of viral proteins, assembly of progeny virions, and egress. For most viruses, genome replication and assembly take place in specialized intracellular compartments known as viral factories or inclusions, which are often composed of membranous scaffolds, viral and cellular factors, and mitochondria. Viral inclusions (VIs) serve multiple purposes during infection, including the concentration of viral and host factors to ensure the high efficiency of replication, sequestration of viral nucleic acids and proteins from innate immune responses, and the spatial coordination of consecutive replication cycle steps. Most double-stranded RNA (dsRNA) viruses form cytoplasmic inclusions with a characteristic morphology. These neoorganelles constitute sites of genome replication and virion assembly, and contain abundant viral RNA and proteins.
The combination of ultrastructural and functional studies has enhanced our knowledge about VI biogenesis. However, for many viruses, it is still not known how these structures form and mediate functions in viral replication. Here, we describe the current understanding of the morphogenesis and function of reovirus inclusions and compare these neoorganelles with the replication factories formed by other members of the Reoviridae family.
The application of NGS to the unbiased mass sequencing and bioinformatic analysis of total nucleic acids extracted from biological samples obtained from a wide range of sources has led to an explosive increase in the number of complete or near-complete viral genomes. For example, a recent study using NGS to sequence the transcriptomes of arthropods representing 70 species from four classes (Insecta, Arachnida, Chilopoda, and Malacostraca) identified 112 novel viruses, many of which are represented by complete or near-complete genomes. The novel viruses encompass the entire taxonomic diversity of previously known families and/or genera of (-) ssRNA viruses and include divergent viruses with entirely novel and unusual genome architecture. Similarly, sequence analysis of the transcriptomes of animals of more than 220 species sampled across nine metazoan phyla (Arthropoda, Annelida, Sipuncula, Mollusca, Nematoda, Platyhelminthes, Cnidaria, and Echinodermata), as well as chordates of the subphylum Tunicata (salps and sea squirts), resulted in the discovery of 1445 RNA viruses, mostly represented by complete or near-complete genomes. Based on phylogenetic analysis of RNA polymerase (RdRp) domain sequences, the novel viruses included clades representing many established families of plant and animal RNA viruses, as well as at least five clades that are so divergent that they are considered as likely new virus families or orders. Also, the sequencing of transcriptomes of gut, liver, and lung or gill tissue of fish, reptiles, amphibians, and birds identified 214 novel vertebrate-associated viruses, representing every family or genus of RNA virus associated with vertebrate infection, including those containing important human pathogens (orthomyxoviruses, arenaviruses, and filoviruses). These and other similar studies have heralded a new era in virology, revealing new dimensions in viral biodiversity and providing largely unexpected insights into the deep evolutionary history of viruses. However, only a minor subset of newly discovered viruses has been subject to full phenotypic characterization which can provide critical and fundamental insights into their biology and virus-host interactions, ultimately transforming our understanding of the evolutionary forces that shape the virosphere and disease emergence. Realistically, as important as these discoveries are to the advancement of science, very few of the viruses will ever cause human disease or influence the global economy.
This mass sequencing approach, which has been called viral metagenomics, can also be applied in a more targeted way to identify viruses in clinical cases of diseases of unknown etiology or to survey for potentially novel zoonotic viruses that may represent a significant risk of transmission to humans. Indeed, NGS is being used increasingly in conjunction with real-time PCR as a front-line tool in medical and veterinary settings for rapid detection and identification of exotic or unknown emerging viruses. For example, in 2009, an outbreak of acute hemorrhagic fever occurred in Mangala, Democratic Republic of Congo (DRC), involving three human cases, two of which were fatal. As no positive diagnosis was obtained using real-time PCR for known viral hemorrhagic fevers in Africa, NGS was conducted on acute phase serum collected from the surviving patient, revealing the near-complete sequence of a novel rhabdovirus, Bas-Congo virus (BASV; species Bas Congo tibrovirus). Although the disease was attributed by the investigators to the novel virus, no isolate was obtained and there was no evidence of neutralising antibodies in 43 serum samples from undiagnosed hemorrhagic fever cases or 50 random serum donors from the DRC. Subsequently, NGS of blood collected from healthy individuals from Nigeria identified two related viruses, Ekpoma virus 1 (EKV-1; species Ekpoma 1 tibrovirus) and Ekpoma virus 2 (EKV-2; species Ekpoma 2 tibrovirus), and a serological survey indicated that antibodies to these or similar viruses occur commonly in healthy humans in Nigeria. However, once again, neither virus was isolated. Interestingly, several other tibroviruses had previously been isolated from healthy cattle or biting midges (Culicoides spp.) in Australia and Florida. None have been associated with either disease in livestock or the infection of humans. These and other studies raise important issues regarding the significance of NGS data, even when providing complete or near-complete viral genome sequences, when investigating disease etiology. Most viruses can cause asymptomatic infections and many newly discovered viruses may be benign in their natural host. Therefore, in the absence of a virus isolate which can be used for experimental studies, establishing a causal association with disease based only on detection of the viral genome should be approached cautiously.
Exposure to airborne pathogens is a common denominator of all human life. With the improvement of research methods for studying airborne pathogens has come evidence indicating that microorganisms (e.g., viruses, bacteria, and fungal spores) from an infectious source may disperse over very great distances by air currents and ultimately be inhaled, ingested, or come into contact with individuals who have had no contact with the infectious source [2–5]. Airborne pathogens present a unique challenge in infectious disease and infection control, for a small percentage of infectious individuals appear to be responsible for disseminating the majority of infectious particles. This paper begins by reviewing the crucial elements of aerobiology and physics that allow infectious particles to be transmitted via airborne and droplet means. Building on the basics of aerobiology, we then explore the common origins of droplet and airborne infections, as these are factors critical to understanding the epidemiology of diverse airborne pathogens. We then discuss several environmental considerations that influence the airborne transmission of disease, for these greatly impact particular environments in which airborne pathogens are commonly believed to be problematic. Finally, we discuss airborne pathogens in the context of several specific examples: healthcare facilities, office buildings, and travel and leisure settings (e.g., commercial airplanes, cruise ships, and hotels).
Emerging infectious diseases under this category were subcategorized into 1a, 1b and 1c. Subcategory 1a covers known pathogens that occur in new ecological niches/geographical areas. A few past examples belonging to this subcategory are the introduction and spread of West Nile virus in North America; chikungunya virus of the Central/East Africa genotype in Reunion Island, the Indian subcontinent and South East Asia; and dengue virus of different serotypes in the Pacific Islands and Central and South America.18,19,20,21,22,23 Factors that contributed to the occurrence of emerging infectious diseases in this subcategory include population growth; urbanization; environmental and anthropogenic driven ecological changes; increased volume and speed of international travel and commerce with rapid, massive movement of people, animals and commodities; and deterioration of public health infrastructure. Subcategory 1b includes known and unknown infectious agents that occur in new host ‘niches'. Infectious microbes/agents placed under this subcategory are better known as ‘opportunistic' pathogens that normally do not cause disease in immunocompetent human hosts but that can lead to serious diseases in immunocompromised individuals. The increased susceptibility of human hosts to infectious agents is largely due to the HIV/acquired immune deficiency syndrome pandemic, and to a lesser extent, due to immunosuppression resulting from cancer chemotherapy, anti-rejection treatments in transplant recipients, and drugs and monoclonal antibodies that are used to treat autoimmune and immune-mediated disorders. A notable example is the increased incidence of progressive multifocal leukoencephalopathy, a demyelinating disease of the central nervous system that is caused by the polyomavirus ‘JC' following the increased use of immunomodulatory therapies for anti-rejection regimens and for the treatment of autoimmune diseases.24,25,26 Subcategory 1c includes known and unknown infectious agents causing infections associated with iatrogenic modalities. Some examples of emerging infections under this subcategory include therapeutic epidural injection of steroids that are contaminated with Exserhilum rostratum and infectious agents transmitted from donor to recipients through organ transplantation, such as rabies virus, West Nile virus, Dandenong virus or Acanthamoeba.27,28,29,30,31
Infectious diseases have affected humans since the first recorded history of man. Infectious diseases remain the second leading cause of death worldwide despite the recent rapid developments and advancements in modern medicine, science and biotechnology. Greater than 15 million (>25%) of an estimated 57 million deaths that occur throughout the world annually are directly caused by infectious diseases. Millions more deaths are due to the secondary effects of infections. Moreover, infectious diseases cause increased morbidity and a loss of work productivity as a result of compromised health and disability, accounting for approximately 30% of all disability-adjusted life years globally.1,2
Compounding the existing infectious disease burden, the world has experienced an increased incidence and transboundary spread of emerging infectious diseases due to population growth, urbanization and globalization over the past four decades.3,4,5,6,7,8 Most of these newly emerging and re-emerging pathogens are viruses, although fewer than 200 of the approximately 1400 pathogen species recognized to infect humans are viruses. On average, however, more than two new species of viruses infecting humans are reported worldwide every year,9 most of which are likely to be RNA viruses.6
Emerging novel viruses are a major public health concern with the potential of causing high health and socioeconomic impacts, as has occurred with progressive pandemic infectious diseases such as human immunodeficiency viruses (HIV), the recent pandemic caused by the novel quadruple re-assortment strain of influenza A virus (H1N1), and more transient events such as the outbreaks of Nipah virus in 1998/1999 and severe acute respiratory syndrome (SARS) coronavirus in 2003.10,11,12,13,14 In addition, other emerging infections of regional or global interest include highly pathogenic avian influenza H5N1, henipavirus, Ebola virus, expanded multidrug-resistant Mycobacterium tuberculosis and antimicrobial resistant microorganisms, as well as acute hemorrhagic diseases caused by hantaviruses, arenaviruses and dengue viruses.
To minimize the health and socioeconomic impacts of emerging epidemic infectious diseases, major challenges must be overcome in the national and international capacity for early detection, rapid and accurate etiological identification (especially those caused by novel pathogens), rapid response and effective control (Figure 1). The diagnostic laboratory plays a central role in identifying the etiological agent causing an outbreak and provides timely, accurate information required to guide control measures. This is exemplified by the epidemic of Nipah virus in Malaysia in 1998/1999, which took more than six months to effectively control as a consequence of the misdiagnosis of the etiologic agent and the resulting implementation of incorrect control measures.15,16 However, there are occasions when control measures must be based on the epidemiological features of the outbreak and pattern of disease transmission, as not all pathogens are easily identifiable in the early stage of the outbreak (Figure 1). Establishing laboratory and epidemiological capacity at the country and regional levels, therefore, is critical to minimize the impact of future emerging infectious disease epidemics. Developing such public health capacity requires commitment on the part of all countries in the region. However, to develop and establish such an effective national public health capacity, especially the laboratory component to support infectious disease surveillance, outbreak investigation and early response, a good understanding of the concepts of emerging infectious diseases and an integrated country and regional public health laboratory system in accordance with the nature and type of emerging pathogens, especially novel ones, are highly recommended.
Traditionally, emerging infectious diseases are broadly defined as infections that: (i) have newly appeared in a population; (ii) are increasing in incidence or geographic range; or (iii) whose incidence threatens to increase in the near future.6,17 Six major factors, and combinations of these factors, have been reported to contribute to disease emergence and re-emergence: (i) changes in human demographics and behavior; (ii) advances in technology and changes in industry practices; (iii) economic development and changes in land use patterns; (iv) dramatic increases in volume and speed of international travel and commerce; (v) microbial mutation and adaptation; and (vi) inadequate public health capacity.6,17
From the perspective of public health planning and preparedness for effective emerging infectious disease surveillance, outbreak investigation and early response, the above working definition of emerging infectious disease and its associated factors that contribute to infectious disease emergence are too broad and generic for more specific application and for the development of a national public health system, especially in the context of a public health laboratory system in a country. Thus, in this article, emerging infectious diseases are divided into four categories based on the nature and characteristics of pathogens or infectious agents causing the emerging infections; these categories are summarized in Table 1. The categorization is based on the patterns of infectious disease emergence and modes leading to the discovery of the causative novel pathogens. The factors or combinations of factors contributing to the emergence of these pathogens also vary within each category. Likewise, the strategic approaches and types of public health preparedness that need to be adopted, in particular with respect to the types of public health laboratories that need to be developed for optimal system performance, will also vary greatly with respect to each category of emerging infectious diseases. These four categories of emerging infectious diseases and the factors that contribute to the emergence of infectious diseases in each category are briefly described below.
A wide range of infectious disease drivers can be grouped under this category, including climate change, land-use patterns, global trade and travel, migration, and so on. Climate change involves mean temperature increases in many parts of the world, as well as increased likelihood of adverse or even extreme weather events (11–13). Many infectious diseases are temperature sensitive as many vectors and pathogens are dependent upon permissive ambient conditions. There is thus a substantial body of research that collectively demonstrates that warming will increase the transmission of vector-borne diseases in the geographic ranges of their distribution (14–18). Changing temperature and precipitation patterns can affect the habitats and population growth of cold-blooded disease vectors, such as mosquitoes and ticks, as well as the replication rates of infectious diseases within their hosts, and even the rates at which disease-carrying vectors bite humans (18–20).
Among the best substantiated indicators of the observed effects of climate change on infectious disease is evidence of an altitudinal increase of malaria in the highlands of Columbia and Ethiopia (21) and of the northerly expansion of the disease-transmitting tick species, Ixodes ricinus, in Sweden (22). Many modelling studies project significant shifts in the transmission of vector-borne diseases such as malaria (23, 24), dengue (25), and Chikungunya (26) under climate change scenarios, but it is important to note that the extent of observed changes will depend on the presence or absence of mitigating measures, such as vector control or socioeconomic development (27, 28). Other examples of infectious diseases in Europe anticipated to be affected by climate change include West Nile virus (29), salmonella (30), campylobacter, and cryptosporidium (31, 32).
Land-use patterns, meanwhile, are a crucial driver of infectious disease emergence. It has been estimated that more than 60% of human pathogens are zoonotic (i.e. diseases of animals that can be transmitted to humans) (33). Many human land-use activities, including agriculture, irrigation, hunting, deforestation, and urban expansion, can cause or increase the risk of zoonotic and food- and water-borne diseases (33, 34). For example, one consequence of urban sprawl and deforestation is that wildlife may increasingly need to find new habitats in urban or abandoned environments, which could lead to increased human exposures to infectious pathogens. Meanwhile, the density of human population, also associated with increasing urbanisation, has also been shown to be linked to the emergence of many infectious diseases (35).
Intensified global trade and travel, not to mention migration, render political borders irrelevant and create further possibilities for global disease transmission (36–38). There are numerous examples of the arrival, establishment, and spread of ‘exotic’ pathogens to new geographic locations, including malaria, dengue, Chikungunya, West Nile, and bluetongue in recent years, aided by shipping or other trade routes (36). This process is facilitated when the environmental conditions in different parts of the world share common characteristics (36). Meanwhile, numerous vaccine-preventable diseases, such as polio, meningitis or measles, can also be introduced or reintroduced to susceptible populations as a consequence of international travel (39).
Emerging infectious diseases have been defined as, “infections that have newly appeared in a population or have existed previously but are rapidly increasing in incidence or geographic range.” Several features may make them particularly threatening. First, recognizing the disease can be difficult when the first cases appear, especially when the symptoms are non-specific. Second, no vaccine or specific treatment may be known initially. Moreover, heterogeneities in disease transmission may create high-risk groups, such as healthcare workers– and high-risk geographical areas, thereby dramatically enhancing the impact of the outbreak.
The 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong is remarkably illustrative of the above issues: symptoms were similar to pneumonia; the incubation period was long enough for local and international transmission to occur; no vaccine or treatment was available; as much as 21% of cases worldwide were healthcare workers. The outbreak also demonstrated the possible existence of super-spreading events (SSEs), during which a few infectious individuals contaminated a high number of secondary cases. Hong Kong had two SSEs: the first occurred in Hospital X around March 3 and led to about 125 cases; the second occurred in Housing Estate Y on March 19, and led to over 300 cases,. Despite its particularly threatening features, the outbreak was brought under control.
In this context, once the epidemic is detected, spontaneous changes in behavior will occur, and non-pharmacological measures are usually initiated to control the outbreak. The resulting effects of these two phenomena on disease transmission is not easily quantified.
The effective contact rate, which reflects the combined influences of social proximity (the number of contacts per time unit) and the probability of infection through each contact, is an essential determinant of disease spread. Our aim was to estimate the temporal variation of this parameter in the community and hospitals, over the course of the outbreak.
Previously published mathematical models of parameter estimation addressed the issues of temporal variability, or social heterogeneity,. Here we present an approach that deals with both issues, together with the occurrence of SSEs. Then the method is applied to the 2003 SARS epidemic in Hong Kong (SARSID database).
A “disease” is any condition that impairs the normal function of a body organ and/or system, of the psyche, or of the organism as a whole, which is associated with specific signs and symptoms. Factors that lead to organs and/or systems function impairment may be intrinsic or extrinsic. Intrinsic factors arise from within the host and may be due to the genetic features of an organism or any disorder within the host that interferes with normal functional processes of a body organ and/or system. An example is the genetic disease, sickle cell anaemia, characterized by pain leading to organ damage due to defect in haemoglobin of the red blood cell, which occurs as a result of change of a single base, thymine, to adenine in a gene responsible for encoding one of the protein chains of haemoglobin. Extrinsic factors are those that access the host's system when the host contacts an agent from outside. An example is the bite of a mosquito of Anopheles species that transmits the Plasmodium falciparum parasite, which causes malaria. A disease that occurs through the invasion of a host by a foreign agent whose activities harm or impair the normal functioning of the host's organs and/or systems is referred to as infectious disease [1–3].
Infectious diseases are generally caused by microorganisms. They derive their importance from the type and extent of damage their causative agents inflict on organs and/or systems when they gain entry into a host. Entry into host is mostly by routes such as the mouth, eyes, genital openings, nose, and the skin. Damage to tissues mainly results from the growth and metabolic processes of infectious agents intracellular or within body fluids, with the production and release of toxins or enzymes that interfere with the normal functions of organs and/or systems. These products may be distributed and cause damage in other organs and/or systems or function such that the pathogen consequently invades more organs and/or systems.
Naturally the host's elaborate defence mechanism, immune system, fights infectious agents and eliminates them. Infectious disease results or emerges in instances when the immune system fails to eliminate pathogenic infectious agents. Thus, all infectious diseases emerge at some point in time in a given population and in a given context or environment. By understanding the dynamics of disease and the means of contracting it, methods of fighting, preventing, and controlling are developed [2, 5, 6]. However, some pathogens, after apparent elimination and a period of dormancy, are able to acquire properties that enable them to reinfect their original or new hosts, usually in increasingly alarming proportions.
Understanding how once dominant diseases are reappearing is critical to controlling the damage they cause. The world is constantly faced with challenges from infectious diseases, some of which, though having pandemic potential, either receive less attention or are neglected. There is a need for constant awareness of infectious diseases and advances in control efforts to help engender appropriate public health responses [7, 8].
The Food and Agriculture Organization of the United Nations has recently estimated that the world equid population exceeds 110 million (FAOSTAT 2017). Working equids (horses, ponies, donkeys, and mules) remain essential to ensure the livelihood of poor communities around the world. In many developed countries, the equine industry has a significant economical weight, with around 7 million horses in Europe alone. The close relationship between humans and equids, and the fact that the athlete horse is the terrestrial mammal that travels the most worldwide after humans, are important elements to consider in the transmission of pathogens and diseases, amongst equids and to other species. The potential effect of climate change on vector ecology and vector-borne diseases is also of concern for both human and animal health.
With this Special Issue, which assembles a collection of communications, research articles, and reviews, we intend to explore our understanding of a panel of equine viruses, looking at their pathogenicity, their importance in terms of welfare and potential association with diseases, their economic importance and impact on performance, and how their identification can be helped by new technologies and methods. Beyond their potential risk to other species, including humans, equine viruses may also represent an interesting model for reproducing virus infection in the host species.
Dennis et al. contributed a review on African Horse Sickness (AHS). This disease, caused by the orbivirus AHS virus (AHSV), induces a very high mortality rate that can exceed 95% in its most severe form. This disease mostly occurs in southern African countries, but its transmission by Culicoides biting midges is of great concern in the current context of global warming and its consequence on displacement of vector populations. In the absence of treatment, prevention is essential, and Dennis et al. also provide a comprehensive review of the different vaccine strategies and technologies available and in current development against AHSV. While live attenuated and inactivated AHSV vaccines have played a role to reduce the impact and occurrence of AHS in affected areas, the number of AHSV serotypes in circulation and their lack of DIVA markers (differentiating infected from vaccinated animals) is a drawback that leads to the development of a new generation of vaccines, such as poxvirus-vectored or reverse genetics vaccines. Lecollinet et al. reviewed major viruses inducing encephalitis in equids and their growing importance as a threat to the European horse population. Amongst them, equid herpesviruses (EHVs) are some of the most frequently isolated equine viruses worldwide. The equine herpesvirus type 1 (EHV-1) is of particular interest to the equine industry because of the different forms of disease it can induce, from a mild respiratory infection to abortion, neonatal death, and myeloencephalopathy (EHM). A communication from Preziuso et al. and an article from Sutton et al. specifically focused on EHV-1 strain characterization in order to better understand EHV circulation in Italy and France. Different approaches were compared, from the single-nucleotide point (SNP) mutation in ORF30 (historically associated with abortive or neuro-pathogenic strains), to other ORF gene sequences and the newly described multilocus strain typing methods (MLST;). The MLST method is an interesting new approach for EHV-1 and a potential epidemiological tool that could provide an alternative until the development of more accessible EHV whole-genome sequencing methods. EHV-1 strain characterization by Sutton et al. allowed to conclude that the surge of EHV-1 outbreaks reported in France in 2018 was not linked to the introduction and/or circulation of a new EHV-1 strain in the French horse population. The origin of this crisis could be linked to a shortage of EHV vaccine and a subsequent reduced rate of EHV vaccination in the preceding years. Lecollinet et al. also reviewed less frequently isolated encephalitis viruses, which may be zoonotic, such as rabies virus, borna disease virus, and West Nile virus (WNV). In the case of WNV, both horses and humans are highly susceptible to viral infection through infected mosquitoes. Unprecedented circulations of WNV have been observed in several European countries in the last decade, with a potential role of climatic and environmental conditions. Both species are considered as dead-end hosts. However, the horse could be used as a sentinel species to monitor and control vector-borne virus activity. Other enzootic flaviviruses were also reviewed, such as Tick-Borne Encephalitis virus (TBEV) and Louping Ill virus (LIV). In Europe, vaccination is only available against some of these pathogens (i.e., EHV-1 and 4, Rabies virus, and WNV), which highlights the importance of surveillance. Taking into account that most of these viruses will induce similar clinical signs of disease, the development of discriminative diagnostic tools is also of increasing importance. Finally, the review presents some other vector-borne (mosquitoes or midges) equine encephalitis viruses, not currently circulating in Europe, from the Flaviridae family (i.e., the Japanese encephalitis virus (JEV), Saint Louis encephalitis virus (SLEV), and Murray Valley encephalitis virus (MVEV)) or the alphaviruses from the Togaviridae family (i.e., eastern, western, and Venezuelan equine encephalitis viruses; EEEV, WEEV, and VEEV, respectively). In relation to VEEV, Rusnak et al. presented systematic approaches for strain selection and propagation of virus and challenge material for the development and approval of a VEEV vaccine under the FDA Animal Rule and the different animal models available (rodents and non-human primates).
Altan et al. have used metagenomics to identify viruses in horses with neurological and respiratory diseases. The equine hepacivirus (EqHV) was detected in the plasma from several neurological cases. This virus, which was first reported in horses in 2012, was further investigated by Badenhorst et al., with a specific focus on its circulation in Austria and the potential role of mosquitoes in its transmission. The prevalence of EqHV in the Austrian horse population studies reached 45% (based on serological evidence), with around 4% of samples positive for EqHV RNA. No EqHV RNA was found in mosquitoes collected across Austria, raising questions about its methods of transmission. Some aspects of this particular question of EqHV transmission were treated by Pronost et al., who presented evidence to support a potential in utero transmission of EqHV from the mare to the foal, based on three positive clinical cases amongst 394 dead foals screened for the presence of EqHV RNA (prevalence of 0.76%). Altan et al. also detected two copiparvoviruses, the equine parvovirus-hepatitis (EqPV-H) and a new one named Eqcopivirus by the authors, with no specific and/or statistical association with disease. Equine parvovirus-hepatitis was also the subject of the article from Meister et al., which reported an EqPV-H infection occurrence in a quarter of the actively breeding Thoroughbred horse population from northern and western Germany. EqPV-H prevalence reached 7% and 35% (EqPV-H DNA positive detection and seroconversion, respectively). This study concerned mostly Thoroughbred brood mares, which represented 97% of the analyzed cohort. Concerning Thoroughbred stallions, Li et al. identified a new equine papillomavirus (EcPV9) in the semen from an Australian Thoroughbred stallion suffering from a genital wart. The clinical significance of this new equine papillomavirus remained to be determined and will require further investigation. A similar question was raised by Nemoto et al., who reported the first detection of equine coronavirus (ECoV) in Irish equids suffering from diarrhea. At five occasions, ECoV RNA was detected in feces from more than 400 equids with enteric diseases. However, the association with disease remains to be substantiated. While ECoV prevalence in Irish equids was 1.2% when measured by rRT-PCR in feces samples, evidence of ECoV infection was significantly higher when measured by serology in 984 serum samples from Dutch horses, 100 serums from Icelandic horses, and 27 paired serum samples from an ECoV outbreak in the USA. Zhao et al. developed and validated an S1-protein-based ELISA for this purpose. Seroprevalence ranged from 26% in young horses to nearly 83% in adults. The authors highlighted the potential use of this ELISA as a diagnostic test to confirm ECoV outbreaks, as a complement to feces samples analysis by qRT-PCR. The study from Back et al. shed some light on the potential role of equine rhinitis A virus (ERAV) infection in poor performance. This longitudinal study, which involved 30 Thoroughbred racehorses, significantly associated seroconversion to ERAV and subsequent failure to attend races. However, similarly to EqPV-H and ECoV infections previously reported in this Special Issue, a direct association of ERAV infection with clinical signs of disease could not be confirmed in this study.
Finally, Fatima et al. investigated the antiviral activity of the equine interferon-mediated host factors myxovirus (Mx) protein (eqMx1) against a range of influenza A viruses (IAVs). The authors highlight the potential protective role of eqMx1, which primarily targets the virus nucleoprotein (NP), against the transmission of new IAVs in horses (i.e., eqMx1 could only inhibit the polymerase activity of IAVs of avian and human origin but remained inactive against the equine IAVs tested). Introduction of a new IAV in the equine population is considered a rare event. In 1989, an equine influenza epizootic was reported in the Jilin and Heilongjiang provinces of northeastern China, with up to 20% mortality, which is quite high when compared with conventional equine influenza outbreaks. The IAV strain representative of this outbreak (i.e., A/equine/Jilin/1/1989) was closely related to an avian H3N8 IAV. The authors show that the IAV strain A/equine/Jilin/1/1989 bears two adaptive NP mutations that confer resistance to eqMx1. To date, equine influenza virus remains one of the most important respiratory pathogens of horses worldwide, with a potential damaging impact on the equine industry, as clearly illustrated in 2007 in Australia and in 2019 in Europe.
We hope this Special Issue helps to highlight the diversity of equine viruses and their importance, in terms of welfare and/or economic impact, to equids and humans.
Bluetongue (BT) is a non-contagious, arthropod-borne viral disease of domestic and wild ruminants, listed as a notifiable disease by the World Organization for Animal Health (OIE). The Bluetongue virus (BTV) is the prototype member of the Orbivirus genus within the Reoviridae family (1, 2).
BTV is a double-stranded (ds) RNA virus (3), its genome consists of ten segments (Seg-1 to Seg-10) of linear dsRNA coding 7 structural (VP1–VP7) and 5 non-structural (NS1, NS2, NS3/NS3a, NS4, and NS5) proteins (4) At present twenty-eighth distinct BTV serotypes have been officially recognized based on Seg-2 gene sequence (5, 6). Other putative novel BTV serotypes have also been described (7–11).
Transmission between mammalian hosts and spread of the infection rely mostly on competent Culicoides species (12–14), so the presence of the disease is then strictly related to the distribution of competent vectors (2). Even though they don't seem to be epidemiologically important, vertical and horizontal transmissions have also been described (15–18). For BTV-26, BTV-27 v02 and, probably, BTV-X ITL2015 and BTV-28 transmission by direct contact has been demonstrated or hypothesized (6, 10, 19, 20).
Clinical signs of BT are more severe and most commonly observed in sheep or in white-tailed deer, often leading to animal fatality especially in naïve animals (1, 2). In cattle, BTV infection is usually asymptomatic, although symptoms were reported after infection with some strains (21–24).
As a RNA virus with a segmented genome, BTV can undergo reassortment which can occur when a cell is simultaneously infected with more than one BTV strain and involves the packaging, into a single virion, of full length of genomic segments of different ancestry. Reassortment in BTV is very flexible, and can involve any genome segment (25–27). However, the genome sequence of BTV isolates generally reflects their geographic origins (28–30).
Seg-2 and Seg-6 encoded the BTV outer capsid proteins VP2 and VP5. They represent the primary target for neutralizing antibodies generated during infection of the mammalian host (31–33). Their highly variable sequences are associated with virus serotype (particularly in VP2/segment) (34–36) and, within each serotype, with the geographic origin of the virus strain (28, 34–37).
Among BTV serotypes, Seg-2/VP2 sequences of BTV-3, BTV-16, and BTV-13 are closely related. All of them are included within the nucleotype B reflecting a serological relationship (3). BTV-3 strains can be subdivided into at least two main clusters. 1st cluster includes strains originated from Africa, Mediterranean Basin and North America (western topotypes, w); 2nd-includes strains originated from Japan, India, and Australia (eastern topotypes, e). The nucleotide (nt) identity between Western and Eastern topotype Seg-2 can be as small as 71.5% (7, 38–43).
Between 2016 and 2018, two novel BTV-3 western strains have been identified in two different geographical areas of Tunisia-one in the north-eastern part of the country (Peninsula of Cap Bon, prototype BTV-3 TUN2016) and the other in the South-East near by the border with Libya (prototype strain BTV-3 TUN2016/Zarzis). The BTV-3 TUN2016 spread in 2017 to Italy infecting a single 3-year-old female crossbred sheep belonging to a flock located in the municipality of Trapani, Sicily, which are 150 km distant from Peninsula of Cap Bon (7, 39, 40) and in 2018 in the Southern area of Sardinia causing numerous outbreaks (38). Clinical signs in infected sheep included depression, fever, nasal discharge, submandibular edema, and crusted discharge around the nostrils. Four animals died because of the severity of infection (38). In 2016, another BTV-3 strain closely related to TUN2016/Zarzis strain was detected in Egypt (38).
The present paper reports the results of the diagnostic activities on BTV conducted at Kimron Veterinary Institute between 2013 and 2018 and the evidence of BTV-3 circulation in Israel. Clinical signs of infected sheep, goats and cattle along with the genetic characterization and phylogenetic analysis of the BTV-3 strains are also described.
For a long time, children’s infectious diseases have been the number one disease type to harm children’s health and threaten children’s lives. With the continuous development of medical undertakings, although human beings have made brilliant achievements in controlling and defeating children’s infectious diseases, the harm and threat of children’s infectious diseases are still very serious today. Children’s infectious diseases are prone to various complications threatening children’s lives; therefore, understanding the occurrence and changes of children’s infectious diseases is of great significance to the prevention and treatment of infectious diseases and the promotion of children’s health.
Infection surveillance is important in infectious disease management and prevention. The surveillance of notifiable diseases in China was first initiated in the 1950s. Accurate and timely surveillance of infectious diseases laid the foundation for effective disease control and prevention in China. After the severe acute respiratory syndrome (SARS) crisis in 2003, the Chinese government strengthened the construction of the public health information system. China officially initiated the China Information System for Disease Control and Prevention (CISDCP) in January 2004. This system is the most comprehensive and macroscopic notifiable disease surveillance system in China. Timely analysis of notifiable disease surveillance data to understand epidemic trends and their main characteristics is the basis for the prevention and control of infectious diseases.
Zhejiang province, located in the southeastern coast of China, has moist air, a mild climate, a developed economy, and large population mobility. It covers an area of 101,800 km2 and is one of the most densely populated provinces in China. By 2017, the population has reached up to 56 million, and the population aged 0–14 years is about 7.5 million.
In this paper, we described epidemiological characteristics of notifiable diseases in children aged 0–14 years reported in Zhejiang Province in 2008–2017, for the purpose of providing a reference for the prevention and control of infectious diseases in children in Zhejiang Province. The results are reported as follows.
The emergence of new infectious diseases, many of which are caused by RNA viruses, is a major threat to human, animal and plant health and agriculture. RNA viruses demonstrate remarkable capacity to evolve due to large population size, short generation times and high mutation and recombination rates. Many are also vector-borne, potentially increasing the prevalence and range of a given virus in natural ecosystems. Understanding the mechanisms underlying viral emergence is key for the rational design of antiviral therapies and control strategies. A first step in this process is the characterisation of the true distribution of virus genetic variability, both spatially and taxonomically across different host species. Recent research has demonstrated that there exists a vast diversity of previously undiscovered viruses in the natural environment. For example, a large number of “insect-specific” flaviviruses have been discovered recently in numerous culicine mosquito species (Diptera: Culicidae: Culicinae) and these viral strains are likely to vastly outnumber the pathogenic strains present in the natural environment, including those flaviviruses that cause diseases such as yellow fever and dengue fever in humans. A variety of other novel RNA and DNA viruses have been recently identified in insects. Deep sequencing technologies have the potential to provide an unprecedented description of this genetic background, and thus to begin to understand the interactions of pathogenic and “silent” viruses in nature, which may include competitive exclusion, superinfection, recombination and other mechanisms that may be involved in the generation of viral diversity.
Invertebrates, including dipterans (order Diptera, the two-winged flies) such as mosquitoes, respond to viral infection via RNA interference (RNAi) or RNA silencing, leading to suppression or elimination of the pathogen via sequence-specific degradation of homologous RNA sequences into small RNAs (sRNAs) of discrete sizes. This has been demonstrated in Stegomyia aegypti [=Aedes aegypti] mosquitoes infected with dengue virus (DENV) or Sindbis virus (SINV), Culex quinquefasciatus mosquitoes orally exposed to West Nile virus (WNV) and Drosophila infected with flock house virus (FHV). Similarly, studies in RNAi-deficient Anopheles gambiae mosquitoes showed increased viral dissemination rates and titres of inoculated O’nyong-nyong virus. In this study, we used sRNAs sequenced from mosquitoes and chironomids sampled from the natural environment to inform total RNA deep sequencing of samples of particular interest. Within the mosquitoes, the vast majority of flaviviruses discovered to date have been isolated from culicine mosquito species (subfamily Culicinae, see examples above) as opposed to anopheline mosquitoes (subfamily Anophelinae, for example An. gambiae, a major vector for malarial parasites, see example above), despite the fact that species from both groups of Culicidae take bloodmeals. In contrast, the chironomids (Diptera: Chironomidae) are non-biting midges. We planned to sample all three groups in order to test whether related viruses may be discovered in a range of dipterans in the natural environment, potentially related to a shared environment and/or transmission and maintenance cycles aside from blood-feeding.
Clinical laboratories are rapidly adopting viral species-specific nucleic acid amplification for virus identification, thereby increasing the sensitivity of detection and reducing the time needed for diagnosis. Although widely successful, these methods are limited for detecting divergent viruses due to their high specificity. Failure rates in determining the etiological cause of disease are varied. For example, the rate for encephalitis is between 30–85% [reviewed in], approximately 12% for acute flaccid paralysis, and for non A-E hepatits between 18–62% [reviewed in]. In cases where routine screening fails, newer technologies are now being employed. Prominent among these are microarrays and sequence-independent amplification and sequencing of viral nucleic acids,,,,,,,,,,.
Viral microarrays can be used to screen for all viral families simultaneously and have been used successfully to detect novel human rhinoviruses, human coronaviruses, and a human gamma retrovirus closely related to mouse retroviruses. Microarrays require sufficient sequence similarities between virus and array oligonucleotides for hybridization to occur, making the detection of highly divergent viruses problematic. Sequence-independent amplification of nuclease protected viral particles abrogates the need for a priori sequence information, allows the detection of viruses recognizable through their protein sequence homologies to known viruses and has successfully been used to identify novel human and bovine parvoviruses,,, polyomaviruses,,, anelloviruses, an arenavirus, a dicistrovirus associated with honey bee colony collapse disorder, and a seal picornavirus.
In this study we utilized sequence-independent amplification of partially purified viral nucleic acid from mouse tissue followed by low-scale shotgun sequencing to quickly identify the viral agents in five samples negative by tests available at the time of inoculations. Of the five viruses identified, two belonged to the Picornaviridae family, and three to the Reoviridae family.
Genomic information offers the opportunity for more personalized treatment and prevention in clinical practice and public health settings. Until recently, such efforts have focused largely on common, complex diseases (for example, cancers, heart disease, neurodegenerative diseases) and less common inherited diseases; examples of such efforts include risk screening, diagnostic sequencing and pharmacogenomics. Now there is growing interest in the application of genomics to the management of infectious diseases and epidemics, which are among the top global public health burdens. Rapid and large-scale sequencing of pathogen genomes, which provides stronger and more accurate evidence than was previously possible for source and contact tracing, is being applied widely for disease outbreak management - most recently and publicly in the case of the Ebola outbreak in West Africa. Additional uses include precise diagnosis of microbial infection, describing transmission patterns, understanding the genomics of emerging drug resistance and identifying targets for new therapeutics and vaccines. There is growing evidence that, as well as pathogen genetic factors, host genetic factors and the interaction between host, vector and pathogen influence variability in infection rates, immune responses, susceptibility to infection, disease progression and severity, and response to preventive or therapeutic interventions. As such, genomic research is improving our understanding of infectious disease pathogenesis and immune response and may help guide future vaccine development and treatment strategies [11–18].
While the past few years have seen substantial federal and private research funding for infectious disease genomics research, there has been little discussion of the possible ELSIs - for individuals, groups or larger society - of using genomic information in the management of infectious disease. This gap may be explained in part by the current paucity of scientific advances in genomics that have practical applications to infectious disease management. Although it may be premature, we must nevertheless anticipate the possibility of ELSI-associated challenges in the future. This Opinion aims to anticipate what some of these issues might be and under what conditions they could arise. We argue that these considerations - even as the science is still developing - should become part of the agenda of researchers, clinicians, policymakers and public health officials so that the benefits of genomic applications to infectious disease are maximized while potential harms to individuals and populations are minimized.
We begin by acknowledging the existing scholarship on ELSI issues in the genomics of non-communicable diseases, and the ethical and legal issues surrounding infectious disease management. Then we briefly describe some of the epidemiologic characteristics and recent genomic advances associated with four particular infectious diseases - Ebola, pandemic influenza, hepatitis B and tuberculosis - that have large-scale public health consequences but differ in terms of ease of transmission, chronicity, severity, preventability and treatability, factors which affect a range of ELSI issues. In this section we also consider the situations under which the use of genomic information might or might not be appropriate in the management of infectious diseases. Finally, we describe some of the major ethical, legal and social issues that arise in the context of genomics and how they may play out in the management of these four specific infectious diseases.
The Reoviridae family is a large and diverse group of nonenveloped, icosahedral viruses with genomes composed of 9–12 linear molecules of double-stranded RNA (dsRNA). Reoviruses are divided between the Spinareovirinae subfamily (species with turrets on the core particle) and Sedoreovirinae subfamily (species with smooth, nonturreted core particles). They infect numerous host species, from plants to crustaceans, insects, aquatic and terrestrial vertebrates. Among the 16 Reoviridae genera, the Orbivirus genus (subfamily: Sedoreovirinae) is the largest, having 22 species recognized by the International Committee on Taxonomy of Viruses (ICTV) and a significant number of species proposals. Orbiviruses are vector-borne pathogens, primarily transmitted by ticks and other hematophagous insects (mosquitoes, Culicoides biting midges and sand flies). Their wide host range includes wild and domestic ruminants, camelids, equids, humans, marsupials, bats, sloths and birds. The most studied orbiviruses are the Culicoides-borne Bluetongue virus (BTV, type species), African horse sickness virus (AHSV) and Epizootic hemorrhagic disease virus (EHDV), all known as important pathogens of livestock and wildlife. Some orbiviruses such as Tribeč virus, Kemerovo, Lebombo and Orungo viruses have been detected in human infections and are considered human pathogens.
Orbiviral genomes consist of 10 linear segments of dsRNA designated by their decreasing molecular weight. They encode seven structural proteins (VP1–VP7) and three to four nonstructural proteins (NS1, NS2, NS3/NS3a and NS4). The high conservation degree of certain structural core proteins (e.g., polymerase, major core and subcore proteins) recommends them for comparative and phylogenetic analyses of different Orbivirus species. In contrast, the proteins of the outer capsid are highly variable and their specificity to the host’s neutralizing antibody response can be used to distinguish between different serotypes of the same orbivirus species. The phylogenetic clustering of Orbivirus members results in clades indicating their putative or potential arthropod vectors: Culicoides- or sand fly-borne (C/SBOV), mosquito-borne (MBOV) and tick-borne orbiviruses (TBOV). One exception to this classification is St. Croix River virus (SCRV), a distant member of the genus considered to be a “tick orbivirus” (TOV), having no known vector.
As one of Europe’s largest wetlands, the Danube Delta Biosphere Reserve (DDBR) located in the southeast of Romania, is a very biodiverse and heterogeneous complex of ecosystems. The region is a major hub for bird migration along main African–Eurasian fly corridors, with ecoclimatic conditions suitable for abundant and diverse populations of arthropod vectors, which may allow pathogen import and maintenance.
During an arbovirus survey in DDBR, we identified a novel orbivirus in grass snakes (Natrix natrix Linnaeus 1758), tentatively named Letea virus (LEAV) after the eponymous village from the study area. The aims of this study were to characterize the genome of LEAV and its evolutionary relationship with other members of the Orbivirus genus. This is the first report of reptiles as orbivirus hosts. The present study expands our knowledge of orbivirus host range, ecology and the complete genomic data may help understand the evolutionary relationship among species of the Orbivirus genus.