Emerging Diseases of Animals

This chapter introduces a proposed scheme for use as a reference in placing animal pathogens into biosafety classifications. The importance of an accepted animal disease classification is apparent; however, the universally accepted guidelines for placing pathogens that only infect animals into biosafety risk categories are poorly defined compared with the guidelines for human pathogens. A biosafety classification scheme for animal pathogens is not intended to place undue burden on researchers but to enhance the quality of research and efforts to improve animal health. The natural starting point for proper biosecurity classification of strict animal pathogens is risk assessment. A consensus on animal pathogen risk groups was reached at the 5th International Veterinary Biosafety Workshop in 1996. The emphasis of biosafety risk classification was on pathogens that infect only animals (not affecting human health). Laboratory work allows the containment and control of infectious materials during procedures by utilizing standard laboratory practices and techniques and also specialized primary barrier equipment. Animals (livestock and poultry species) infected with disease agents present unique challenges for biosecurity control.

This chapter reviews the microbiological risks of xenotransplantation as they currently exist, with the caveat that the technical tools of molecular biology are rapidly adding to our knowledge in leaps and bounds. The ethical issue for xenotransplantation from the microbiological aspect is the risk of introducing an unknown infectious agent into a naive human population versus the individual benefit of a life-giving organ transplantation and improved quality of life. There is a large database of information on pigs, from basic anatomy and physiology to specifics of their biochemistry and genome. Production of pigs in barrier facilities operated under very high standards of animal husbandry can consistently yield qualified-pathogen-free animals. The gibbon ape leukemia virus (GALV) behaves as an exogenous retrovirus, but DNA evidence points to the endogenous retrovirus of Mus caroli as the origin. Certainly, the expanding interest in pigs as organ donors has placed the subject of endogenous retroviruses, in particular the porcine endogenous retrovirus (PERV), front and center in the microbiological risk analysis of xenotransplantation. PERV mRNA has been identified at variable levels in all tissues examined, indicating that viral expression is not restricted. Transmission electron microscopy of tissues was negative, although virus-like particles (VLP) were detected in serum. Although the VLP did not bind antibodies against recombinant gag or whole virus, product-enhanced reverse transcriptase analysis produced positive results.

In general, influenza viruses replicate in epithelial cells of the upper respiratory tract or gastrointestinal tract, and the outcomes of such infections include no clinical signs, upper respiratory disease, pneumonia, and occasionally death. In birds, most infections are subclinical. However, in poultry, influenza infections have caused clinical respiratory disease or drops in egg production, and a few specific avian influenza virus strains have caused severe disseminated infections with systemic disease and high death losses. Interspecies transmission between different hosts within separate classes is even less frequent, as has occurred rarely with chicken-to-human or free-flying duck-to-pig transmission. One exception to the above rule has been the ease and frequency of transfer of swine H1N1 viruses to turkey breeder hens, but these are sporadic and isolated occurrences. The ability of influenza viruses to spread and produce infectious progeny and lesions is related to the cleavage of the hemagglutinin in various cell types. In mammals, influenza viruses primarily replicate in the respiratory tract and cause associated clinical signs and lesions. Virus replication occurs predominantly in the epithelium of the nasal cavity and results in clinical rhinitis, the most frequent clinical presentation in human patients, horses, and pigs. In Minnesota, traditional and molecular epidemiology has demonstrated the direct transfer of mildly pathogenic avian influenza viruses from free-flying birds (primarily mallard ducks) to range turkeys reared outdoors during annual wild-bird migrations.

There are currently six named species of Brucella plus the newly discovered group of brucellae infecting marine mammals. Brucella melitensis is primarily a disease of goats and sheep that is present in most areas of the world where goats are raised. In humans, B. melitensis is considered the principal cause of brucellosis and is clinically the most severe. In the United States, disease caused by B. melitensis in animals is considered exotic, and nearly all cases of human infection are due to the consumption of imported unpasteurized goat cheese. Bison migrations outside Yellowstone National Park (YNP) boundaries have occurred with increased frequency since 1980, usually during the winter. When the bison migrate onto private land, they pose a potential threat of spreading brucellosis to domestic cattle, thereby putting the state's class free status at risk. The development of effective strategies to control and eradicate brucellosis from bison and elk in the greater Yellowstone area (GYA), from feral swine across the southern and central states, from reindeer and caribou in the arctic, and perhaps finally from marine mammals presents an unprecedented challenge. With the continuing emergence of this disease and these disease issues in free-ranging populations of wildlife, solutions can only be found based on good science, public education, and innovative, collaborative work between research scientists, regulatory and wildlife veterinarians, and wildlife managers.

Enterohemorrhagic Escherichia coli, or pathogenic Shiga toxin-producing E. coli (STEC), is distinguished from other pathogenic E. coli by its ability to produce Shiga toxins designated Stxl, Stx2, Stx2c, and Stx2e. E. coli O157:H7 is highly pathogenic, possesses numerous virulence factors, and is the most common cause of STEC disease in humans in many parts of the world. The accumulation of virulence factors into pathogenicity islands may have resulted from continued acquisition of genes from bacteriophages or plasmids that integrate at common integration sites such as the bacterial tRNA genes. The prevalence of E. coli 0157:H7 was higher in herds that weaned calves abruptly than in herds that used a variety of methods to gradually wean calves. Some of the most numerous bacterial species in the rumen and colon, such as Bacteroides spp. and Prevotella spp., can hydrolyze esculin to the aglycone esculetin, thus producing inhibitory aglycones in the gastrointestinal tract. The major inhibitory factor under aerobic conditions is pyocyanin and under anerobic conditions appears to be fluorescein. The possibility of adding specific feed substances, feed additives, or competitive exclusion bacteria to the diets of cattle to reduce fecal shedding and rumen proliferation of STEC is promising but will require further study. Ruminants used as food are an important source of food-borne STEC infections in humans. Shedding of STEC is widespread in healthy cattle throughout the world.

Carrión's disease, the first identified bartonellosis, is a hemolytic, vasculoproliferative disorder of people in the Andes Mountains of Peru, Colombia, and Ecuador. The disease, caused by Bartonella (Rochalimaea) quintana, went largely ignored until late in the 20th century, when it was found as a complicating infection of immune-compromised people causing a condition termed bacillary angiomatosis (BA). Two new pathogenic species, B. henselae and B. elizabethae, were also isolated from BA patients. Erythrocyte invasion is a strategy utilized by Bartonella spp. Blood or tissue culture is one of the most clinically useful tools to document active infection. B. henselae bacteremia can persist in clinically healthy cats for months to sometimes years. The presence of bacteremia can be intermittent or recurrent in some cats, making multiple sampling necessary. Blood for culture should be taken in an aseptic manner and placed into sterile EDTA tubes or directly into centrifugation-lysis tubes. Blood samples can be frozen and thawed prior to culture to produce erythrocyte lysis, which improves the sensitivity of isolation and rapidity of colony formation. Vaccination of cats would seem desirable to decrease potential human exposure to Bartonella. Cats that are treated and recover from Bartonella bacteremia following experimental intradermal infections with cultured organisms appear to be resistant to homologous strains on rechallenge.

Mycobacterium tuberculosis and Mycobacterium bovis are members of a closely related group of organisms referred to as the M. tuberculosis complex, which also includes Mycobacterium africanum and Mycobacterium microti. M. tuberculosis is the primary cause of tuberculosis in humans and, world wide, is the leading cause of death from a single infectious agent. Animals with potential exposure to M. bovis through contact with infected cattle are skin tested and, in some cases, slaughtered to prevent the spread of tuberculosis to new herds. Tuberculosis caused by M. bovis and M. tuberculosis has been reported in zoos, game parks, and other exotic animal collections in the United States and throughout the world. The presence of a wildlife reservoir of tuberculosis in Michigan may prevent the United States from achieving the goal of eradication of tuberculosis in animals. To comprehend the pathogenesis of a disease, it is important to understand the routes of infection and mode of transmission between hosts as well as the host response and characteristics intrinsic to the pathogen. Tuberculosis in animals is chiefly acquired by inhalation or ingestion. Follow-up surveys of the wildlife in the area revealed no further evidence of tuberculosis in any of the wild animals that were examined. The best long-term approach to control of tuberculosis in the United Kingdom appears to be the development of a vaccine for cattle and improved diagnostic tests to discriminate infected from vaccinated cattle.