HEALTH HAZARDS TO HUMANS ASSOCIATED WITH DOMESTIC PETS'

Aiutu. Rev. Public Health 19%. 17:221-15 HEALTH HAZARDS TO HUMANS ASSOCIATED WITH DOMESTIC PETS' Marshall Plaut, Eugene M. Zimmerman, and Robert A. Goldstein Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 KEY WORDS: asthma, hypersensitivity diseases, bites by animals, infectious diseases, immunocompromised patients ABSTRACT Allergy to pets, particularly when manifested as asthma, is an important health hazard. The health impact of severe clinical disease associated with allergy to pets can be minimized by avoidance of pets. Many individuals with milder disease keep their pets and obtain medications for relief of their allergy symptoms. Bird fancier's disease can result in profound deterioration of pulmonary function, and requires avoidance of bird exposure. Animal bites are the commonest health hazard of domestic pets and result in tissue damage and infection risk. Bites are treated by cleaning the wound, and appropriate use of antibiotics and tetanus prophylaxis. Diverse infectious diseases are transmitted to humans by their pets; these diseases are particularly dangerous to immunocompromised individuals. The infectious diseases can be partly prevented by avoiding ill animals and by washing of hands following exposure to pets or petderived secretions. They can be treated by appropriate antibiotics and/or specific immune globulins andor vaccines. INTRODUCTION This review discusses the potential health hazards to humans from their pets. These hazards are divided into three categories of diseases: (a) immunologic responsiveness to pets, resulting in allergic disease, asthma, andor hypersensitivity pneumonitis; (b) bites and or scratches from pets, which cause tissue damage and may induce infections, and (c) infectious diseases associated with pets. Table 1 gives an overview of the major diseases reviewed in this chapter, and the pets responsible. 'The US Government has the right to retain a nonexclusive, royalty-free license in and to any copyright covering this paper. 22 1

Table 1 Diseases associated with domestic pets Disease IMMUNOLOGICAL DISEASE Allergic diseases Asthma Hypersensitivity pneumonitis INJURY Bite, scratch (laceration, puncture, contusion, infection risk) INFECTIOUS DISEASES Campylobacteriosis (Campylobacter jejuni Campylobacter coli) Capnocytophaga canimorsus (DF-2) Leptospirosis Lyme disease (Borrelia burgdorferi) Meliodosis (Pseudomonas pseudomallei) Mycobacteria marinwn Pasteurella mulrocida Plague (Yersinia pestis) Rat-bite fever (Streptobacillus moniliformis and (in Asia) Streptobacillus minus) Salmonellosis (not S. ryphi) Tetanus Tularemia (Francisca tularensis) Yersiniosis (Yersinia enterocolitica and Yersinia pseudotuberculosis) Fungal diseases Cryptococcosi s Histoplasmosis Ringworm (Microsporum, Trichophyton) Sporotrichosis (Sporothrix schenckii) Parasitic diseases Cestiodiasis (Hymenodepsis nana) Cryptosporidiosis Cutaneous larva migrans (Ancylostoma braziliensis, Ancylostoma caninwn) Echinococcosis (Echinococcus granulosis) Ectoparasites [Clieyletiella infestation and sarcoptic mange (scabies) (Sarcoptes scat iei) ] Giardiasis Toxoplasmosis (Tmoplasma gondii) Visceral larva mtgrans (Toxocara Canis, Toxocara catr) Chlamydial and rickettsial diseases Cat scratch disease (Bartonellosis)(Bar- tonella henselae) Chlamydiosis (Psittacosis) Rocky Mountain spotted fever (Rickettsia rickettsii) Viral diseases Rabies Lymphocytic choriomeningitis Pet Cat (commonest), dog; rarely, hamster, rabbit, rodent, bird Same as allergic diseases Birds (pigeon, budgerigar, canary, chicken) Dog (commonest), cat; others including rodent. bird Dog, cat, horse, hamster Dog, cat (rare) Dog, rat, cat (rare) Mice, dog Fish (exotic) Fish Cat, dog, rabbit, rodent (bite) Cat, dog, rabbit Rodent, cat (rare) Chicken, dog, cat, rabbit, rodent, ferret, turtle, iguana, other reptiles Dog, cat (bites) Rabbit, rodent; rarely bird, dog (bite), cat (bite) Rodent, cat. dog, rabbit Pet birds, especially pigeons Birds (especially starlings) Cat, dog, rabbit, rodent, ferret, horse Cat, dog, rodent Hamster and other rodents Cat, dog, ferret, rodent. reptile (rare) Dog, cat Dog (rare) Cat, dog, rabbit Dog, cat, rodent, ferret, bird Cat; rarely dog Dog, cat, ferret Cat, rarely dog Psittacine (parrots) and domestic birds Dog, rabbit Dog, cat, ferret Hamster and other rodents

HEALTH HAZARDS OF PETS 223 The review focuses on pet-related diseases in the United States. Parasitic and other infectious diseases transmitted by pets are much more frequent in some countries than in the United States, but these are not described unless they occur in the United States. This review emphasizes allergic diseases and, in particular, the most important clinical manifestation of allergy to pets, asthma and rhinitis. Advances in understanding the pathophysiology of allergic diseases and asthma have resulted in a new view: Pet (especially cat) exposure is more important in asthma than previously appreciated (59,63). The magnitude of exposure to cat and other allergens is an important determinant of asthma severity and perhaps of irreversible reduction in pulmonary function. ALLERGY TO PETS Definition Allergic diseases are characterized by the production of IgE antibodies directed against proteins or glycoproteins that serve as antigens. Those proteins and glycoproteins that induce an IgE antibody response are a subset of antigens, called allergens. Once IgE antibody molecules are present, allergen cross-links the IgE antibody and induces mediator release from mast cells and basophils. As described below, these mediators are responsible for increases in blood vessel permeability, smooth muscle tone, mucus production, and inflammatory cell accumulation that are the manifestations of allergic diseases. Atopic patients, with a genetic predisposition to allergic diseases, express one or more of the three major allergic diseases: allergic rhinitis, asthma, and atopic dermatitis. Among the most common manifestations of allergy to pets are allergic rhinitis, allergic conjunctivitis, and asthma. Other allergic diseases less commonly induced by pet allergens include atopic dermatitis (eczema) and urticaria. The immune mechanisms involved in atopic dermatitis are poorly understood. Allergic rhinitis, asthma, conjunctivitis, and urticaria are mediated, at least in part, by IgE antibodies (62). Allergic rhinitis is characterized by an inflammatory infiltrate in the nasal mucosa, and is associated with symptoms of sneezing and nasal congestion. The disease may be complicated by sinusitis. Allergic conjunctivitis is characterized by an inflammatory conjunctival infiltrate, associated with pain, itching, and redness of the conjunctiva. Asthma is defined (23a) as a lung disease with the following characteristics: 1. Airway obstruction (or airway narrowing) that is reversible (but not completely so in some patients) either spontaneously or with treatment; 2. Airway inflammation; 3. Airway hyperresponsiveness to a variety of stimuli.

224 GOLDSTEIN ET AL Diagnosis The diagnosis of allergy to pets consists of medical history, physical examination, and laboratory tests establishing that (a) the patient makes IgE antibody to allergens derived from the pet; and (b) the patient is exposed to the pet (i.e. allergen is found in deposited house dust and/or in the air of the home or other environment) (58). If a pet lives in the home, the allergen will certainly be there. Pet-derived allergen may be found in homes even if the pet is not there (see below). Other diagnostic procedures include nasal and/or bronchial challenge with allergens; andor exposure to the pet in a rmm containing a controlled ventilation system, a more natural setting than challenge with soluble allergens. Medical history reveals the symptoms of allergic diseases, which lead to diagnoses of rhinitis andor asthma andor atopic dermatitis, conjunctivitis, and urticaria. Most pet-allergic individuals are atopic, in that they have a familial tendency to produce IgE antibodies to a large number of the aeroallergens to which they are exposed. Thus, in addition to symptoms from pet exposure, they react to many other allergens. They usually have symptoms of allergic rhinitis corresponding to seasons when certain plants pollinate. It may be difficult to distinguish between allergic disease induced by pets vs other allergens. Relationship of Exposure to Symptoms Pet exposure may induce acute and/or chronic symptoms. Acute symptoms can most readily be linked to the pet. For example, if symptoms develop within minutes of entering an environment with a pet, then the pet is a possible or likely cause of the symptoms. Chronic symptoms are difficult to relate to specific environmental exposures. The most useful diagnostic test is a reduction in symptoms related to prolonged removal from pet exposure (73). Because it is virtually impossible to remove residual cat or dog allergen rapidly from a home even after removing the pet, it is useful for the patient to move, temporarily, to a pet-free environment. Laboratory Tests Laboratory tests are important for establishing that individuals are sensitized to pet allergens, i.e. they produce IgE antibodies to the allergens, which can be determined by skin testing or by testing the blood. Pathophysiology The relationship between pet exposure and clinical symptoms requires two separable events: sensitization (induction of an IgE antibody response) and symptoms (seen following aeroallergen exposure by a sensitized individual).

HEALTH HAZARDS OF PETS 225 The capacity of individuals to make an IgE antibody response to airborne allergens (aeroallergens) depends upon the genetic background of that individual. Atopic individuals do make IgE antibodies to allergens, whereas most individuals are nonatopic and do not make IgE antibodies to these allergens (62). The capacity to make an IgE response also depends upon the extent of allergen exposure; allergen concentrations above a minimal threshold substantially increase the likelihood of stimulating IgE antibody production in atopics. Thus, atopic individuals produce IgE antibodies to a wide variety of aeroallergens. As a high proportion of atopic individuals are frequently exposed to cats and dogs, which both express allergens, not surprisingly, a high proportion of atopic patients are allergic to these pets. Prolonged exposure and exposure to high concentrations of allergen are both risk factors for the production of IgE antibodies to allergens from pets (24). Approximately 20% of the population of the USA is atopic, and approximately 117 of these atopic individuals (i.e. 3% of the population) is allergic to cat allergens, while a smaller fraction is allergic to dog allergens (26, 32). While most individuals with allergy to pets are atopic, some individuals are not atopic and may have IgE antibody predominantly against pet allergens. For example, one group of elderly patients with asthma have been described who are not atopic but are allergic to cats (45, 54). Induction of Disease In sensitized individuals, repeated allergen exposure stimulates a variety of allergic symptoms including allergic rhinitis and asthma (and perhaps atopic dermatitis). However, only some allergic patients have clinical manifestation of asthma. The reasons why the pathology involves distinct target organs (i.e. nose or lung) are not known. The most severe clinical allergic disease (other than acute anaphylaxis) is asthma, which is present in about 5% of individuals in the United States (10) and is associated with high economic costs, high morbidity, and occasional mortality. Allergy to pets is important because IgE antibody to pet allergens, like other indoor allergens, is a significant risk factor for asthma. Indeed, exposure to cat or dog allergen can (rarely) induce fatal and near-fatal asthma (13). In contrast, IgE antibody to outdoor allergens like ragweed pollen or grass pollen is a risk factor for allergic rhinitis but, in most patients, is not a risk factor for asthma (59, 63, 71). Relationship of Indoor Allergens to Asthma The induction of asthma by pet allergens (and other indoor allergens) may reflect some combination of the following seven factors: high concentrations of airborne allergens in a closed environment; long-term exposure to high concentrations of allergens; other as yet unidentified factors in the environment, like pollutants; the nature and size of the particle that carries the allergen;

226 GOLDSTEIN ET AL biochemical properties of the allergen (e.g. many allergens have protease activity); genetic factors; and age when exposed to allergen. Allergens Associated with Pets A series of allergens derived from pets have been identified (60). For example, the major cat allergen is found in the saliva and on the fur. Cat allergens are widely distributed, presumably because they adhere to many surfaces (e.g. furniture, carpeting, clothing) (22, 27, 50, 86). This property means that (a) individuals who contact pets in their own home may bring substantial amounts of pet allergen into environments that they visit; and (b) once the allergen is in a new environment, it persists unless extraordinary cleaning measures are undertaken (49, 51). Thus schools with no cats have substantial levels of cat allergen in dust (49,52), as do homes without cats (although generally at lower concentrations). The particle distribution of cat allergen has been determined. In an undisturbed room, 25% of cat allergen is on small particles (4.5 p) and thus will be airborne and readily deposited on the respiratory tract of individuals in a room containing allergen (46). In contrast, the major allergen of house dust mite is on large particles and is not airborne in an undisturbed room. The Natural History of Cat Allergy Asthma is a clinical diagnosis, and the definition of asthma (see above) includes the phrase: Airway obstruction (or airway narrowing) that is reversible (but not completely so in some patients). Asthma is associated with long-term irreversible, but relatively slow, worsening of pulmonary function. There is no information about the long-term natural history of asthma due to pet allergens, but one study of laboratory animal allergy indicates that asthma induced by laboratory animals is not progressive, in that bronchial reactivity remained constant over a 12-month period of allergen exposure (53). Based on our present knowledge of the natural history of asthma, asthma induced by pet allergens is likely associated with a (slow) deterioration of pulmonary function, given continued and long-term exposure. Age of Exposure Exposure to allergen in infancy appears to be a risk factor for the development of allergy and asthma. Dust mite exposure at age <2 predisposed to both IgE antibody to house dust mite and asthma at age 10; other data have confirmed and extended the original study. Pet exposure at ages 0-5 years correlates with wheezing at ages 8-13 (72).

Treatment HEALTH HAZARDS OF PETS 227 Treatment of allergy to pets consists of at least four approaches (27, 84): removal of pet; extensive cleaning, removal of carpets, air filtration, and denaturation; symptomatic treatment with standard medication ( pharmacotherapy ); and immunotherapy REMOVAL OF PET: EXTENSIVE CLEANING TO REMOVE ALLERGEN The major reasons to remove the pet are (a) the importance of pet allergen exposure on both the induction and the severity of asthma; and (b) the possible importance of pet allergen exposure on long-term irreversible deterioration of pulmonary function tests. Removal of the pet is considered to be effective in diminishing the severity of asthma and allergic diseases induced by the pet, yet pets are not always removed. Indeed, many individuals whose livelihood depends on pets (e.g. veterinarians) attempt to continue to work with pets after making some attempts to reduce exposure. The risks and the benefits of pet ownership need to be balanced. Management of asthma now focuses on using antiinflammatory glucocorticoids and of allergen avoidance. The rationale of pet allergen avoidance is based in part on research studies of asthma in a cat room, a room with controlled ventilation in which cats live, and into which cat-allergic patients are brought for varying periods of time, as an in vivo challenge model (81). Antiinflammatory medications (glucocorticoids) do block cat-induced rhinitis and asthma symptoms, but only partially (85). The magnitude of symptoms induced in a cat room may be quite high, and these symptoms are not entirely relieved by antiinflammatory medications. The results also suggest that heavy allergen exposure induces airway inflammation (53,s 1,85), possibly by stimulating production of high concentrations of proinflammatory cytokines. Thus, reduction in allergen exposure is necessary to control airway inflammation, perhaps by reducing cytokine production. Allergen avoidance may be important for modifying the long-term natural history of asthma (59, 60, 84). If early intervention to avoid pet allergens prevents deterioration in pulmonary function, then pet allergen avoidance is critical for maintenance of lung function. These types of results suggest that allergen avoidance is extremely important for at least some patients with allergy to pets. In contrast, pet allergen avoidance may be of limited clinical efficacy because (a) in many individuals, pet allergens are either not the most important allergen or are not the only important allergen; and (b) the physical and chemical properties of pet allergens make it extremely difficult to remove these allergens from the environment. Thus, allergy to pets occurs typically in atopic individuals who are allergic

228 GOLDSTEIN ET AL to multiple allergens. In cold, dry andor mountain environments, IgE antibody to cats is the predominant risk factor for asthma (50,52,76). However, other allergens are also important even in these environments. In temperate climates, house dust mite, not pet, is considered the major indoor (and asthma-inducing) allergen, and in some inner-city environments, cockroach allergens may be most important (59-6 1). Pet allergen avoidance may have limited clinical efficacy in patients in whom pet allergens are not the most important ones. After removal of the pet, removal of pet-derived allergens requires aggressive cleaning, and removing of carpets and upholstery (51,60). With the most effective cleaning strategies, it may take six months after removal of cats before cat allergen concentrations are reduced. Although frequent washing of cats, in conjunction with other measures such as removing furniture and improving air filtration, has been reported to be effective in reducing airborne cat allergen concentrations (6), other data suggest that washing of cats does not significantly reduce levels of cat allergens (41). Even when the home environment is cleaned, exposure may recur because allergen is encountered at many environments elsewhere. Some data suggest that the development of allergic diseases and asthma may be prevented by avoiding allergens in infancy (38). However, the protocols used up to now suggest that the magnitude and duration of this prevention effect appears to be limited. SYMPTOM RELIEF Symptom relief of rhinitis involves the use of antihistamines, decongestants, nasal cromolyn, and intranasal glucocorticoids. Symptom relief of asthma involves the use of beta-adrenergic agents (usually inhalers), cromolyn, and glucocorticoids. These agents are useful even for moderate and severe asthma, but they are not effective unless they are used in combination with environmental controls to reduce allergen exposure. Avoidance of house dust mite allergen is effective in reducing symptoms of asthma (59-61). Although similar studies have not been performed with pet allergens, it is likely that allergen avoidance would be effective clinically. IMMUNOTHERAPY Altering the immune response by repeated injections of allergens has been used as specific treatment in allergic patients who continue to be exposed to the allergens. None of the newer approaches to immunotherapy has yet been shown to be superior to standard immunotherapy. One consistent effect of immunotherapy is to increase substantially the specific IgG antibody response. It is considered to be contraindicated in certain diseases where IgG antibody, and not just IgE antibody, induces some of the pathophysiological changes (e.g. pigeon breeder s disease-see below). Although immunotherapy reduces symptoms (e.g. upon exposure in a cat room) and allergen responsiveness in cat allergy (37, 55, 82), it is not clear

HEALTH HAZARDS OF PETS 229 that it is as effective as cat allergen avoidance. There are data suggesting that an important clinical effect of immunotherapy is to reduce the intensity of late-phase reactions (62), perhaps by some (poorly understood) antiinflammatory effect. As noted above, antiinflammatory glucocorticoids are only partially effective when patients are heavily exposed to cats. We hypothesize that immunotherapy with cats will be only partially effective if patients are heavily exposed to cats. Allergens Derived from Pets Other Than Cats Allergy to any pet is possible. Contact with virtually any pet can induce IgE antibody production to some allergens and can induce allergic rhinitis or asthma. Since cats and dogs have the run of the indoor environment, these pets are associated with the highest and second highest frequency of IgE antibody production, and asthma. For other pets that are often kept in cages, high concentrations of allergens are limited to the environment around the cages. Allergens are shed on animal fur and bird feathers and on droppings in the cages. Of course, exposure to the environment of the cages, depending on the amount of time exposed, and activities such as cleaning the cages increase the likelihood of sensitization. Rats, mice, rabbits, guinea pigs, and hamsters also induce allergy in susceptible individuals (both laboratory animal workers and people who own these animals as pets) (74). Birds also induce sensitivity (e.g. pigeon, budgerigar, canary, chicken, etc) (48, 83). Exposure to multiple birds increases the likelihood of an immune response. Pigeon breeders disease is associated with an IgE response (associated with rhinitis and asthma) and/or other immune responses (associated with inflammatory alveolitis), as discussed below (28,29). IMMUNOTHERAPY FOR ALLERGENS DERIVED FROM PETS OTHER THAN CATS There is limited information on this subject. It is reported that immunotherapy with dog allergens is not effective clinically (37). There is insufficient information on the basic mechanisms of immunotherapy to explain this clinical ineffectiveness. BIRD FANCIER S DISEASE Immune reactions to bird antigens in some patients are remarkably similar to reactions to cat and dog allergens: immediate hypersensitivity reactions, including asthma, upon exposure to birds (29, 48, 83). Rhinitis and asthma are presumably mediated by IgE antibodies (just as rhinitis and asthma to cats and dogs). The precise antigens of birds have not yet been identified in bird droppings, feathers, and/or serum proteins (77).

230 GOLDSTEIN ET AL In addition to immediate hypersensitivity reactions, bird exposure may induce a different type of inflammatory reaction in the lung, called hypersensitivity pneumonitis or extrinsic allergic alveolitis (28, 29). (Bird exposure can induce immediate reactions, alveolitis, or both.) Alveolitis is presumed to be induced by the immune response to antigens carried on small particulates that reach the lung alveoli. The reaction is reproduced by antigen inhalation and is dose dependent. Most patients are exposed chronically to large numbers of buds kept in cages in a closed environment. In the United States, pigeon breeders disease is the most frequent example of this alveolitis. Symptoms are related to the intensity of exposure (hours per day of exposure x the number of pigeons). Almost all symptomatic breeders, and 50% or more of asymptomatic breeders, produce IgG antibodies to pigeon proteins (against pigeon IgA, pigeon IgG, and pigeon mucin), although the identity of the pathogenic protein is unclear (79). Many patients with hypersensitivity pneumonitis have laboratory evidence of nonspecific activation of the immune response, such as increased total IgG levels. In addition to specific IgG antibodies, patients also have cell-mediated immune responses to bird antigens. IgE antibodies are thought to be irrelevant to hypersensitivity pneumonitis since hypersensitivity pneumonitis induced by other antigens, such as farmer s lung disease, is not associated with IgE antibodies. It is not known whether asthma and alveolitis are induced by the same, or different, bird-derived antigens. Inhalation challenge to pigeon-dropping extracts or pigeon serum induces immediate and late symptoms and changes in pulmonary function. Immediate reactions include bronchospasm in some patients; the late reaction is quite different in patients with alveolitis from that in asthmatic patients, in that it consists of fever, alveolitis, and pulmonary function changes consistent with restrictive lung disease (28, 29, 65). The birds that induce alveolitis include budgerigars, pigeons, canaries, and chickens. Breeders are typically exposed to 20 or more pigeons for several hours per day for several years before becoming symptomatic. Approximately 6-21 % of pigeon breeders have symptoms of alveolitis. For example, one recent study found that, among pigeon breeders in the Canary Islands, 31% had rhinitis, 19% had asthma, 15% had symptoms resembling chronic bronchitis, and 8% had symptoms resembling alveolitis (66). Treatment of alveolitis consists of (a) avoidance of antigen, and (6) systemic glucocorticoids. The alveolitis is reversed in many patients when exposure is avoided (28, 29, 40), but fibrotic changes (which also occur in some patients upon chronic antigen exposure) are irreversible. BITES BY PETS Bites represent the commonest type of hazard of pets. In the United States, there are anestimated 1-2milliondogbitesand400,000catbiteseachyear. Thesemay

HEALTH HAZARDS OF PETS 23 1 be profound underestimates, as only 10% of bites receive medical attention (9). Dogs are by far the commonest source of bites (63 to 93% of bites). Physicians are seen because of the severity of bite, fear of rabies or tetanus, and/or consideration of legal action. Bite wounds represent 1% of emergency room visits. These bites can cause abrasion, laceration, puncture or crush injuries, and may get infected. The potentially serious infectious complications include septic arthritis and osteomyelitis. Some dogs can generate enormous forces in their jaws, which can cause crush injuries. Deaths from pet bites, though rare, are usually due to dog bites, which can cause massive blood loss from very young children; pit bulls are the most commonly identified dog that can kill. Cats cause significant puncture injuries that can penetrate joints, but these injuries are often overlooked because cat teeth are small. Bites are generally from one s own pet (e.g. breaking up a fight between dogs) or the pet of an acquaintance; caution is needed in invading a dog s territory (33). Treatment includes evaluation of the severity of injury and of the risk of infection, wound cleaning, and in certain circumstances, debridement (5, 25). The major infectious organisms to be considered are mixed flora (in dogs); Pasteurella multocida (which causes rapid-onset infections; it is in 26% of dog wounds but is the major infectious organism in cat oral flora and is in 50% of cat wounds); Capnocytophaga canimorsus; and rabies and tetanus (36). Because of concern of infection, some physicians recommend that all patients with pet bites should receive prophylactic antibiotics. Tetanus prophylaxis (e.g. a booster immunization with tetanus toxoid in a previously immunized individual) is indicated. In individuals with remote (>lo years) immunization with tetanus toxoid and/or with a severe wound, both a tetanus toxoid booster and tetanus immune globulin are given. INFECTIOUS DISEASES Many infectious diseases are termed zoonoses because they are transmitted by animals, including domestic pets (I 1, 16,43,47,58a). Humans are infected either by direct contact with pets (e.g. with the skin, nasopharyngeal or respiratory secretions, urine, or feces), or by indirect contact (with water or food that has been contaminated with infectious secretions of the pet). In addition, pet ownership is a risk factor for infections with agents that are transmitted by means other than direct or indirect contact. Two examples of the latter are the tick-transmitted diseases, Lyme disease and Rocky Mountain spotted fever. Although these diseases are usually not transmitted by pets, on occasion the ticks are carried by the pets to the vicinity of humans, and the ticks then bite humans. Some of these infectious diseases are mild. However, there are more severe and even fatal variants of these diseases. Reduction of infectious diseases

232 GOLDSTEIN ET AL transmitted by pets can be partially achieved by avoiding contact with animals less than six months of age and animals with diarrhea. Since many pets that carry infectious agents do not appear ill, an additional preventive measure is to wash hands thoroughly after contact with pets, their secretions, or potentially contaminated food and water derived from pets. Immune Protection from Infectious Diseases in Immunocompromised Patients Deficient function of one or more components of the immune response of immunocompromised individuals increases susceptibility to certain infectious agents. The deficient immune component most commonly associated with increased susceptibilty to pet-transmitted infections is cell-mediated immunity. The immunocompromised patients not only are more susceptible to acquiring infections, but also are more likely to develop a severe form of the infection. The immunocompromised patients for whom precautions on exposure to pets and pet-derived secretions are most critical are (a) patients being treated with immunosuppressive agents, and (b) patients with HIV infection. Infants and elderly individuals may also need to observe precautions. These precautions include not only avoiding young and sick animals and thorough handwashing after contact with pets and pet secretions, but also two more stringent measures: avoiding all contact with pet feces and potentially contaminated water; and avoiding all contact with reptiles or amphibians (the latter because of the risk of Salmonella infections). Immunocompromised patients are at risk of the following pet-transmitted disease: three bacterial infections [campylobacteriosis, Mycobacterium marinum infections, and salmonellosis (not S. typhi)]; two fungal infections (cryptococcosis and histoplasmosis); three parasitic infections (cryptosporidiosis, giardiasis, and toxoplasmosis); and onerickettsial infection (cat scratch disease). SPECIFIC INFECTIOUS DISEASES The following is a list of important infectious diseases transmitted by pets. Each disease also lists those pets that transmit the disease. Not discussed are several diseases for which pets are known to be reservoirs for the infectious agent, but for which there is no evidence that pets transmit the agent to humans (e.g. group A streptococcal infections, where dogs and cats do harbor the bacteria). Bacterial Diseases CAMPYLOBACTERIOSIS (CAMPYLOBACTER JEJUNI, CAMPYLOBACTER COLI) This bacterial infection has a reservoir in domestic and wild birds and animals. While the commonest mode of transmission is via ingestion of contaminated food or water, some cases are transmitted from contact with pets (4, 58a).

HEALTH HAZARDS OF PETS 233 Infected pets (dogs, cats, horses, and hamsters) shed bacteria in their feces, and this shedding is age dependent (notably in the first year of life) and is increased if the pet has diarrhea. About 2 million cases occur per year in the United States, but only a small minority are due to pet exposure. Epidemiologic analysis shows that contact with animals is not a risk factor for illness, but exposure to pets with diarrhea is a risk factor, accounting for 6.3% of cases (67). Rare cases result from exposure to apparently healthy young pets. The clinical illness is associated with a self-limited gastroenteritis, but occasionally septicemia and death (an estimate of 120-360 deathdyear in the United States) occur from these bacteria. CAPNOCYTOPHAGA CANIMORSUS (DF-2) This organism, found in the oral cavity of dogs and, rarely, of cats is a potential cause of infections following pet bites (36, 58a). In immunosuppressed patients, Capnocytophaga canimorsus (dysgonic fermenter (DF-2)) infection, from dog flora, is a cause of sepsis even in the absence of local signs of infection. This disease is transmitted by urine of sick or carrier animals. LEPTOSPIROSIS Human infection occurs when urine contaminates food or water (11, 16). Mucus membrane contact is an alternate mode of transmission. Rodents are the most common source. Vaccination of pets protects against clinical disease but does not prevent infection following exposure. LYME DISEASE (BORRELIA BURGDORFERI) Household pets are relatively rare sources of this infection. However, pet ownership in rural areas is a risk factor for this disease (70), and dogs acquiring vector ticks may become ill. The ticks carried by the pets may infect the human owners (75). MELIODOSIS (PSEUDOMONAS PSEUDOMALLEI) This is a rare human disease in the United States, but it is more common in Southeast Asia where the organism is endemic. Aquarium tank water with exotic imported fish may be contaminated (16). Bleach disinfection of tanks is recommended to control this disease. MYCOBAOERM MARINUM These are rare infections in public swimming areas. Infection occurs when areas of minor skin trauma are exposed to water contaminated with these organisms. The disease is characterized by cutaneous granulomas. HIV-infected individuals are especially susceptible and can acquire this infection from contaminated aquariums (34). These infections occur from cat and dog bites and PASTEURELLA MULTOCIDA scratches (1 6,36, Sa). This organism, found in the oral flora of most cats and many dogs, induces a cellulitis with very rapid onset (within 24-48 h). Signs

234 GOLDSTEIN ET AL and symptoms include regional lymphadenopathy, chills, and fever. Septic arthritis, osteomyelitis, and tenosynovitis also occur. Treatment is with penicillin or ampicillin, with wound drainage needed at times. PLAGUE (YERSINIA PESTIS) This disease is typically transmitted by rats and other rodents (19, S8a). In endemic areas (i.e. California, Arizona, and New Mexico), cats are infected by eating rodents or by being bitten by rat fleas (17). Thus, oropharyngeal secretions in cats (and occasionally in other pets) are a source of aerosol exposure (31). RAT-BITE FEVER (STREPTOBACILLUS MONILIFORMIS AND (IN ASIA) STREPTOBACIL- LUS MINUS) This disease is usually transmitted by bites from rat and, rarely, cat (16, 36, 43). SALMONELLOSlS (NOT S. TYPHI) Species of Salmonella, other than Sahonelh typhi, have an animal reservoir, and serotyping often can identify the likely reservoir. The most common cause of Salmonella infections is transmission from undercooked food including poultry, meat, eggs, and unpasteurized milk. Transmission from pets (chicken, dog, cat, rabbit, rodent, ferret, turtle, iguana, and other reptiles) accounts for 15-20% of total cases of Salmonella (18). The disease can be transmitted by direct or indirect contact (e.g. with water that pets swim in or drink). About 6040% of pet-associated cases are in children aged 1-9 years, and none of the pet-associated cases occur in individuals over aged SO years. Patients at high risk for pet-transmitted salmonellosis include not only infants and young children, but also patients with HIV infection. Patients with malignancy and with hemoglobinopathies such as sickle cell disease are also at increased risk of salmonellosis, presumably including pet-transmitted salmonellosis. Many species, such as amphibians and reptiles, have high fecal carriage rates without signs of illness. The fecal carriage rates for reptiles is more than 90% (58a). Treating reptiles with antibiotics has not been successful but rather has increased the antibiotic resistance of the Salmonella. The organism is transmitted transovarially so that eggs are infected; in addition, some species such as iguanas eat feces. In the 1970s, the number of households having small pet turtles rose to 4%, with large, parallel, increases in human salmonellosis of turtle-associated serotypes (18). A requirement that turtles be certified Salmonella-free was ineffective in halting cases of turtle-associated serotypes of Salmonella. Thus, in 1975, the FDA banned all interstate shipments of pet turtles in the United States, resulting in a 14% reduction in cases of Salmonella (an 18% decrease in the population ages 1-9 years). More recently, lizards, notably iguanas, have

HEALTH HAZARDS OF PETS 235 become more popular as pets, with over 795,000 green iguanas imported into the United States in 1993; 7.3 million pet reptiles are now present in 3% of homes. Substantial increases in human Salmonella infections of reptile serotypes have occurred concomitantly (14,23). Salmonella typically causes an uncomplicated gastroenteritis that does not require antibiotic therapy (58a). Antimicrobial agents are indicated for patients with underlying diseases listed above, infants, and patients with severe colitis, and for those with invasive Salmonella disease. Effective antibiotics include ampicillin, amoxicillin, trimethoprim-sulfamethoxazole, etc, for gastroenteritis; and chloramphenicol or one of the above agents for invasive salmonellosis. A vaccine for typhoid fever is not effective against the pet-derived serotypes of Salmonella. TETANUS Dog and cat oropharynx contain these organisms, so puncture wounds represent a risk factor for this infection (16,36,43,58a). As discussed in the section on pet bites, tetanus toxoid alone, or with tetanus immune globulin, is useful for preventing such infections. TULAREMIA (FRANCISCA TUURENSIS) The major vectors for this organism in the United States are rabbits, ticks, and rodents; rarely birds, dogs, or cats. Pets may harbor the organism in their oral secretions, so the infection is transmitted by bites, or occasionally by contact with oral secretions (e.g. licking) (44,47, 58a). YERSINIOSIS (YERSINIA ENTEROCOLITICA AND YERSINIA PSEUDOTUBERCULOSIS) These diseases are usually transmitted by contaminated food (meat, milk) or water, but they can be transmitted by infected pets such as rodents, cats, dogs, rabbits (43, 58a). Fungal Diseuses CRYPTOCOCCOSIS This fungal disease is transmitted by inhalation of organisms from bird droppings, especially pigeon droppings. It causes a systemic disease including meningoencephalitis and pneumonia and requires prolonged, combined antifungal systemic therapy (e.g. six weeks for meningitis). The treatment is potentially toxic. For patients at risk, avoidance of areas contaminated with pigeon droppings is advisable. Elderly patients are at somewhat increased risk, and 5 to 10% of patients with AIDS are infected with the organism (15, 34). In patients with advanced HIV infection, prophylaxis with fluconazole is useful in reducing the infection rate. HISTOPLASMOSIS This fungal infection is transmitted in histoplasma-endemic areas (eastern and central United States) by inhalation of soil or dust in barnyards, bat droppings, and bird droppings, especially from starlings. For

236 GOLDSTEIN ET AL high-risk individuals, it is advisable to avoid high-risk activities such as cleaning chicken coops, disturbing soil under bird-roosting sites, and exploring caves (15, 47). These CutanC%XlS fungal agents RINGWORM (MICROSPORUM, TRICHOPHYTON) are transmitted by direct contact with infected animals (cats, dogs, rabbits, rodents, ferrets, and horses) (11, 16, 43, 57). SPOROTRICHOSIS (SPOROTHRIX SCHENCKII) This organism is widely distributed in the soil. It infects pets (cats, dogs, rodents) following wound infection (e.g. cat-fight wounds) and is excreted in the feces. It can be transmitted by direct contact with pet wounds (58a, 64). Parasitic Diseases CESTlODlASlS (HYMENODEPSIS NANA) This tapeworm is transmitted from ingesting eggs after handling rodent species or contaminated food or water. Infection occurs mainly in children (16). CRYPTOSPORIDIOSIS This occurs usually via transmission in contaminated water, and by human to human (fecal-oral) transmission. Contamination from feces of pets Leg. cats, dogs, ferrets, rodents, reptiles (rare)] is a risk factor, although a less common cause of transmission (58a). Children and patients with HIV infections are most susceptible (15, 34). The organism is resistant to chlorine and thus requires effective water filtration systems. CUTANEOUS LARVA MlGRANS (ANCYLOSTOMA BRAZILJENSIS, ANCYLOSTOMA CAN- INUM) While most cases of hookworm infections are transmitted from human to human in rural, tropical, and subtropical areas, on rare occasions human disease, presenting as eosinophilic enteritis, has been transmitted by the feline and canine hookworm, Ancylostoma braziliensis (in the Gulf coast and New World tropics), and more recently by the canine hookworm, Ancylostoma caninurn (68). These latter cases have been identified in Queensland, Australia, mostly in dog owners (21). The precise mode of transmission is believed to be through walking barefoot in soil contaminated by dog feces. In some surveys, more than 20% of dogs not only in Australia but also in the United States have hookworms, and sporadic cases have been seen in the United States; the disease may therefore be more widespread than so far thought (20, 43). ECHINOCOCCOSIS (ECHINOCOCCUS GRANULOSIS) This particular Species Of Echinococcus is acquired by dogs (43). It is a rare disease in the United States,

HEALTH HAZARDS OF PETS 237 but is seen occasionally in endemic areas in Arizona, California, New Mexico, and Utah. Exposure to dog feces-contaminated food or water can result in development of cysts in humans. ECTOPARASITES [CHEYLETIELLA INFESTATION AND SARCOPTIC MANGE (SCABIES) (SARCOPTES SCABIEO] Cheyletiella infestation is transmitted by direct contact from animals (cats, dogs, and rabbits). Scabies is most commonly transmitted by direct human-to-human contact. Direct contact with pets carrying this organism can transmit the disease (43, 57). GIARDIASIS Although humans are the principal reservoir of Giardia infections, pets (dogs, cats, rodents, ferrets, and birds) can be infected and can contaminate water with infectious cysts (58a). Humans are infected by direct contact with feces and with contaminated water. The organism is widely disseminated (depending on location and age, positive cultures are obtained from I-20% of the population of the United States). Patients with cellular immune deficiency (notably patients with HIV infection), with humoral immunodeficiency, and with cystic fibrosis are at increased risk of infection. TOXOPLASMOSIS (TOXOPLASMA GONDII) This protozoa is very common; the cat is the major vehicle for transmission, rarely dogs (47,58a). Serologic tests indicate that 30% of cats, and humans, have been exposed. Cat-to-cat transmission is by the fecal-oral route. Oocytes are excreted in the feces of cats, but become infectious only after sporulating, which requires 1-3 days. Humans are exposed by the fecal-oral route, for example after changing cat litter-boxes. In addition, the organism is found in many animals; raw or undercooked meat is therefore another source of infectious material. The incubation period is approximately seven days. Immunocompetent individuals have subclinical disease, or a mild flulike illness. However, in primary exposure of women during gestation, toxoplasmosis acquired 6-8 weeks before gestation can also be transmitted to the fetus, although this is rare. Infection of women during the first two trimesters of pregnancy results in infection of 50% or more fetuses, with severe clinical disease in 10% or more of fetuses. This congenital disease can present with meningoencephalitis (which may lead to mental retardation and blindness), as well as hepatosplenomegaly, jaundice, and thrombocytopenia (43, 47). Immunocompromised patients, notably those with HIV infections, are at increased risk for acquiring severe form of disease (systemic toxoplasmosis and/or encephalitis), andor reactivation of an endogenous tissue cysts leading to disseminated disease andor encephalitis (15, 34). Pet-transmitted infection, in pregnant women and in HIV-infected individuals, is reduced by extensive handwashing after contact with cat feces or residue

238 GOLDSTEIN ET AL of cat feces in sandboxes or in soil. More effective measures include avoidance of contact with cat feces. Thus cat litter should be changed daily (i.e. before the oocysts sporulate) by a nonsusceptible individual. Cats should be kept from hunting and ideally be confined indoors and fed only canned or dried commercial food or well-cooked meats. Fresh fruit and vegetables should be well washed. Toxoplasma infections are treated with pyrimethamine and sulfonamides. Immunocompromised patients are at risk of recurrence. Such individuals should have lifetime suppressive therapy, with pyrimethamine plus sulfadiazine and leucovorin. VISCERAL LARVA MIGRANS (TOXOCARA CANIS, TOXOCARA CAT0 The primary cause of visceral larva migrans and ocular larva migrans is the dog roundworm, Toxocara canis. A second but considerably less frequent cause is the cat roundworm, Toxocara cuti. The seroprevalence of infection in children in the United States is between 2 and lo%, with higher rates among minorities (African-Americans, Hispanics) and persons of lower socioeconomic status. This disease is the most frequent of animal-transmitted human infection (12, 35, 47, 58a). Although some cases of toxocariasis are caused by eating contaminated food (lightly cooked liver or other meat), most are transmitted from puppies. Eggs of T. canis are recovered from yards of homes and parks where untreated puppies roam. Nearly all puppies are infected at birth by transplacental larval transmission. Worm eggs are released in the feces of 5- to 6-week-old puppies and contaminate soil. Toddlers with pica are at highest risk of infection. Direct contact does not cause the disease because the eggs are not immediately infectious. Once infected, most children are asymptomatic. Some develop ocular larva migrans (more common in older children), which is typically unilateral and can result in an intense chorioretinitis leading to blindness. Visceral larva migrans (commonest in children aged 14)is associated with eosinophilia, liver granulomas, and occasionally, complications including intractable asthma and encephalitis. Treatment of ocular larva migrans is with antiinflammatory glucocorticoids. The role of antihelmintic drugs is unclear. Treatment of visceral larva migrans is symptomatic, with glucocorticoids effective in reducing the eosinophilic infiltrations in the myocardium and/or central nervous system. The value of antihelminthic agents in killing larva is not known, and the drugs have toxic side effects. Control measures include controlling pets in the household-disposing of visible cat and dog feces (including closing sandboxes, since cats often defecate there), eliminating causes of pica, and treating puppies and kittens with anti-

HEALTH HAZARDS OF PETS 239 helminthics at 2,4, 6, and 8 weeks of age. Thus, an appropriately treated pet is unlikely to transmit the disease to its owner. Chlamydial and Rickettsial Diseases The etiol- CAT SCRATCH DISEASE (BARTONELLOSIS) (BARTONELLA HENSELAE) ogy of cat scratch disease was discovered only recently and was called Rochalimaea henselae, and now Bartonella henselae. Other members of this genus of Rickettsia include Bartonella quintana, Bartonella elizabethae, and Bartonella bacilliformis. These are causes of diseases ranging from bacillary angiomatosis and bacillary peliosis hepatitis, to cat scratch disease, and trench fever. Immunocompromised individuals, including HIV-positive individuals, are susceptible to severe forms of Bartonella infection (15). However, only Bartonella henselae has been linked to cats (42, 80). This bacteria is a cause of bacillary angiomatosis and bacillary peliosis hepatitis (which occurs most frequently in HIV-infected individuals) and cat scratch disease (which occurs most commonly in healthy individuals). There are estimates of up to 9.3 cases per 100,000 (about 22,000 cases) per year in the United States of cat scratch disease (39). The symptoms of cat scratch disease include regional lymphadenopathy, occasionally associated with fever and with skin papules. Complications include encephalitis, hepatitis, and chronic systemic disease; these complications are rare except in immunosuppressed patients. Bacillary angiomatosis is occasionally fatal. The disease is presumed to be transmitted by cat fleas, and it is epidemiologically linked to owning a kitten younger than 12 months and to being scratched, and (less frequently) to being licked in the face by a cat (87). Both ill cats and apparently healthy cats may harbor Bartonella. Dogs may rarely transmit the disease, but the epidemiologic link to cats is very strong. The incubation period is approximately three weeks. Treatment of humans consists of doxycycline or erythromycin; however, this treatment is generally not necessary for healthy individuals, and may not be fully effective in immunocompromised individuals. Psittacosis is a chlamydial disease caused by CHLAMYDIOSIS (PSrnACOsfs) Chlamydia psittaci, which is transmitted by infected birds (11, 13a, 47, 58a, 69). Any species of bird, including members of the parrot family, can be a source of this organism. Imported, exotic birds (some imported illegally), including members of the parrot family, pigeons, and turkeys are common sources (13a). Most patients have had contact with a pet bird. The organism is found in 54% of birds, and certain environments (eg. crowding of birds during shipping) may markedly increase the prevalence of infection in the birds. The birds may be symptomatic or asymptomatic, but continue to shed the organism intermittently for many months. Up to 10% of infected birds may

240 GOLDSTEIN ET AL become chronic carriers. The organism is most commonly transmitted by the airborne route, but all excreted material of the birds, and feathers and dust derived from the birds, are contaminated. Incubation periods following exposure are approximately 7-14 days. Both sporadic and epidemic forms of the illness have been reported. The illness may vary from a acute febrile, flu-like illness with a severe headache, to an atypical pneumonia with a nonproductive cough, but extensive changes detectable by X ray. Prevention involves treating infected birds with a tetracycline antibiotic for 45 consecutive days. Legally imported birds are quarantined and treated with chlortetracycline for 30 days, but this time interval is too short, and some infected birds continue to shed. Birds should be kept isolated from wild birds and from newly arrived birds (e.g. in a pet store). Cages, droppings, and other materials must be disinfected. Untreated patients have a mortality of 20%. Treatment with tetracycline or doxycycline for 10-21 days is effective, and reduces the mortality rate to 1% (47). ROCKY MOUNTAIN SPOTTED FEVER (RICKEVSIA RICKETTSII) This disease is widespread in the south Atlantic, southeastern, and south-central United States in particular, especially in spring and summer. It is transmitted by tick bites. Although the exact role of dogs in transmitting this disease is unknown, it is presumed that dogs carry ticks to the vicinity of humans. Humans exposed to ticks are at increased risk of infection (11, 47, 58a). Viral Diseases RABIES Rabies is a viral disease that infects principally animals. Its primary reservoir consists of wild animals, including bats, raccoons, skunks, foxes, and mongooses; raccoons have become a significant source in parts of the United States (7, 30, 58a); and cats and horses are also potential reservoirs. Dogs are a major reservoir in many countries other than the United States, including Mexico. Dogs may become infected by bites or saliva of infected animals. In the United States, rabies has been well controlled by vaccinating dogs (and cats); in nonendemic areas, 0.1% or less of dogs and cats are rabid. In endemic areas of the United States, 0.1 to 2% of dogs are positive for rabies. In contrast, in developing countries and in parts of Mexico, up to 80% of tested dogs are positive and 90% of human rabies is transmitted by dogs. The infection is usually transmitted by biting, but the virus is present in saliva and is transmissible by licking. Most dogs and cats become ill within five days. Diagnoses can be made by demonstrating viral antigen in the brain. The incubation period in humans is variable but averages two months.

HEALTH HAZARDS OF PETS 241 Symptoms include central nervous system manifestations, commonly including dysphagia and convulsions, with a fatality rate approaching 100% (47, 58a). Although there is considerable fear of rabies transmission from dogs, since untreated rabies is uniformly fatal, the disease is quite rare in the United States (except along the Mexican border); only 200 cases are reported annually despite a population of 50 million dogs. Treatment is typically delayed while the dog or cat from a low-risk area (Le. there are very few positive tests, and the animals are typically vaccinated also) is confined for observation for ten days. Treatment consists of three phases, each of which must be done properly: (a) clean the wound extensively with soap and water (which alone substantially reduces risk); and, if a decision is made to treat, (b) administer rabies immune globulin both into the wound and in the gluteal area and (c) with a separate syringe, administer one of two approved rabies vaccines (human diploid-cell rabies vaccine and rabies vaccine absorbed), on days 3, 7, 14, and 28, intramuscularly in the deltoid area. Treatment is begun as soon as possible after exposure, but empirical data indicate that the average delay after exposure is five days, yet treatment is fully effective. A genetically engineered oral rabies vaccine is currently being tested in humans. LYMPHOCYTIC CHORlOMENINGITIS This is a chronic infection occurring in hamsters and other rodents. Humans are infected by inhalation or ingestion of dust or food contaminated with virus from urine, feces, blood, or nasopharygeal secretions of rodents. Pet hamsters have been implicated as the source of some human infections (16). Surveys indicate that 5% of individuals in large cities in the United States have serologic evidence of infection. Most infections of adults cause mild disease, although some patients develop meningitis. Lymphocytic choriomeningitis virus infection of pregnant women results in transmission of the infection to the fetus. Fetal infection may be complicated by hydrocephalus and chorioretinitis. Any Annual Review chapter, as well as any article cited in an Annual Review chapter, may be purchased from the Annual Reviews Preprints and Reprints service. 1-800-347-8007; 415259-5017; email: arpr@class.org Literature Cited 1. Deleted in proof infection. J. Am. Vet. Med. Assoc. 204: 2. Deleted in proof 57-6 1 3. Deleted in proof 5. Anderson CR. 1992. Animal bites: 4. Altekruse SF, Hunt JM, Tollefson LK, Madden JM. 1994. Food and animal guidelines to current Anim. Bites 92134-49 management. sources of human Cumpylobacrer jejwti 6. Avner D. Woodfolk JA, Platts-Mills

242 GOLDSTEIN ET AL 7. 8. 9. 10. 11. 12. 13. 13a. 14. 15. 16. 17. 18. 19. 20. TAE. 1995. Washing cats: quantitation of Fel di allergen removed by water immersion. J. Allergy Clin Immunol. 95:262 (Abstr.) Baevsky RH, Bartfield JM. 1993. Human rabies: a review. Am. J. Emer. Med. 11:279-86 Deleted in proof Beck AM. 1991. The epidemiology and prevention of animal bites. Semin. Vet. Med. Surg. (Small Anim.) 6:186-91 Benson V, Marano MA. 1994. Current Estimates from the National Health Interview Survey, 1993. Natl. Cent. Health Stat. Vital Health Stat. 10 (190) Beran GW. 1993. Zoonoses in practice. Vet. Clin. N. Am. Small Anim. Pracr. 23: 108s 1107 Buijs J, Boorsboom G, van Germund JJ, Hazebroek A, van Dongen PAM, et al. 1994. Toxocara seroprevalence in 5-year-old elementary schoolchildren: relation with allergic asthma. Am. J. Epidemiol. 140839-47 Call RS, Ward G, Jackson S, Platts- Mills TAE. 1994. Investigating severe and fatal asthma. J. Allergy Clin. Immunol. 941065-72 Cent. Dis. Control Prevent. 1992. Human psittacosis linked to a bird distributor in Mississippi-Massachusetts and Tennessee, 1992. Morbid. Mortal. Wkly. Rep. 41:794-97 Cent. Dis. Control Prevent. 1995. Rep tile-associated salmonellosis-selected states, 1994-1995. Morbid. Mortal. Wkly. Rep. 44347-50 Cent. Dis. Control Prevent. 1995. USPHSllDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: a summary. Morbid. Mortal. Wkly. Rep. 441-34 Chomel BB. 1992. Zoonoses of house pets other than dogs, cats and birds. Pediatr. Infect. Dis. J. 113479-87 Chomel BB, Jay MT, Smith CR, Kass PH, Ryan CP, Barrett LR. 1994. Sere logical surveillance of plague in dogs and cats, California, 1979-1991. Comp. Immunol. Microbiol. Infect. Dis. 17: 11 1-23 Cohen ML, Potter M, Pollard R, Feldman RA. 1980. Turtle-associated salmonellosis in the United States. Effect of public health action, 1970 to 1976. JAMA 243: 1247-49 Craven RB, Maupin GO, Beard ML, Quan TJ, Barnes AM. 1993. Reported cases of human plague infections in the United States, 1970-1991. J. Med. Entomol. 3075841 Croese J, Loukas A, Opdebeeck J, Fair- 21. 22. 23. 23a. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. ley S, Prcciv P. 1994. Human enteric infection with canine hookworms. Ann. Intern. Med. 120:369-74 Croese 1, Loukas A. Opdebeeck J, Prociv P. 1994. Occult enteric infection by Ancylostoma caninum: a previously unrecognized zoonosis. Gastroenterology 1063-12 Custovic A, Taggart SCO, Woodcock A. 1994. House dust mite and cat allergen in different indoor environments. Clin. Exp. Allergy 24: 1164-68 Dalton C. 1995. Iguana-associated salmonellosis in children. Pediarr. Infect. Dis. J. 14319-20 Dep. Health Hum. Serv. 1991. Guidelines for the diagnosis and management of asthma. Natl. Asthma Educ.Program Expert Panel Rep. DHHS Publ. No. (PHS) 91-3042 Desjardins A, Benoit C, Ghezzo H, L'Archeveque J, Leblanc C, et al. 1993. Exposure to domestic animals and risk of immunologic sensitization in subjects with asthma. 1. Allergy Clin. Immunol. 91 :979-86 Dire DJ. 1992. Emergency management of dog and cat bite wounds. Emer. Med. Clin. N. Am. 10719-36 Duff AL. Platts-Mills TAE. 1992. Allergens and asthma. Pediatr. Clin. N. Am. 39:1277-91 Eggleston PA, Wood RA. 1992. Management of allergies to animals. Allergy Proc. 6:289-92 Fink JN. 1992. Hypersensitivity pneumonitis. Clin. Chest Med. 13:303-9 Fink JN. 1993. Hypersensitivity pneumonitis. In Allergy, Principles and Practice, ed. E Middleton Jr, CE Reed, EF Ellis, NF Adkinson Jr, JW Yunginger, WW Busse, pp. 1415-31. St. Louis: Mosby. 4th ed. Fishbein DB, Robinson LE. 1993. Rabies. N. Engl. J. Med. 329:1632-38 Gasper PW, Barnes AM, Quan TJ, Benziger JP, Carter LG, et al. 1993. Plague (Yersinia pestis) in cats: description of experimentally induced disease. J. Med. Entomol. 3020-26 Gergen PJ, Turkeltaub PC. 1992. The association of individual allergen reactivity with respiratory disease in a national sample: data from the second National Health and Nutrition Examination Survey, 1976080 (NHANES 11). J. Allergy Clin. Immunol. 90579-88 Gershman KA, Sacks JJ, Wright JC. 1994. Which dogs bite? A case-control study of risk factors. Pediatrics 93:913-17 GIaser CA, Angulo FJ, Rooney JA. 1994. Animal-associated opportunistic

35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. infections among persons infected with the human immunodeficiency virus. Clin. Infect. Dis. 18:14-24 Glickman LT, Magnaval JF. 1993. Zoonotic roundworm infections. Infect. Dis. Clin. N. Am. 7:717-32 Goldstein EJC. 1992. Bite wounds and infection. Clin. Infect. Dis. 14: 633-40 Haugaard L, Dah1 R. 1992. Immunotherapy in patients allergic to cat and dog dander. 1. Clinical results. Allergy 47 :249-54 Hide DW, Matthews S, Matthews L. Stevens M, Ridout S, et al. 1994. Effect of allergen avoidance in infancy on allergic manifestations at age two years. J. Allergy CIin. Imnmurrol. 93: 842-46 Jackson LA, Perkins BA, Wenger JD. 1993. Cat scratch disease in the United States: an analysis of three national databases. Am. J. Public Health 83: 1707-11 Johnson MA, Nemeth A, Condez A, Clarke SW, Poulter LW. 1989. Cellmediated immunity in pigeon breeders lung: the effect of removal from antigen exposure. Eur. Respir. J. 2:444-50 Klucka CV, Ownby DR, Green J, Zoratti E. 1995. Cat shedding of Fel d 1 is not reduced by washings, Allerpet-C spray, or aceproniazine. J. Allergy Clin. Immunol. 95: I 164-7 1 Koehler JE, Glaser CA, Tappero JW. 1994. Rochalimaea henselae infection. A new zoonosis with the domestic cat as reservoir. JAMA 27 1331-35 Lappin MR. 1993. Feline zoonotic diseases. Vet. Clin. N. Am. Small him. Pract. 2357-78 Liles WC, Burger RJ. 1993. Tularemia from domestic cats. West. J. Med. 158: 6 19-22 Long A, Sparrow D, Weiss ST, O'Connor G, Ardman BS, Jones N, et al. 1995. Sensitization to cat allergen is associated with asthma in older men and predicts airway hyperresponsiveness. J. Allergy Clin. Immunol. 1995: 95:185 (Abstr.) Luczynska CM, Li Y, Chapman MD, Platts-Mills TAE. 1990. Airborne concentrations and particle size distribution of allergen derived from domestic cats (Felis domesticus). Am. Rev. Respir. Dis. 141:36147 Mandell GL. Bennett JE, Doh R, eds. 19XX. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. New York: Churchill Livingstone. 4th ed. HEALTH HAZARDS OF PETS 243 48. 49. 50. 51. 52. 53. 54. 55. 5 6. 57. 58. 58a. 59. Marks MB. 1984. Respiratory tract allergy to household pet birds. Anit Allergy 5256-57 Munir AKM, Einarsson R, Dreborg SKG. 1995. Mite (Der-p-I. Der-f-I), cat (Fel-d-I) and dog (Can-f-I) allergens in dust from Swedish day-care centers. Clin. Exp. Allergy 25: 1 19-26 Munir AKM, Bjorksten B, Einarsson R, Schou C, Ekstrand-Tobin A, et al. 1994. Cat (Fel-d-I), dog (Can-f-I), and cockroach allergens in homes of asthmatic children from three climatic zones in Sweden. Allergy 49508-16 Munir AKM, Einarsson R, Dreborg SKG. 1994. lndirect contact with pets can confound the effect of cleaning procedures for reduction of animal allergen levels in house dust. Pediatr. Allergy Immunol. 5:32-39 Munir AKM, Einarsson R, Schou C, Dreborg SKG. 1993. Allergens in school dust. 1. The amount of the major cat (Fel d I) and dog (Can F I) allergens in dust from Swedish schools is high enough to probably cause perennial symptoms in most children with asthma who are sensitized to cat and dog. J. Allergy Clin. Immunol. 9 1: 1067-74 Newill CA, Eggleston PA, Prenger VL, Fish E, Diamond EL, et al. 1995. Prospective study of occupational asthma to laboratory animal allergens: stability of airway responsiveness to methacholine challenge for one year. J. Allergy Clin. Immunol. 95:707-15 Ohman JL Jr, Sparrow D, MacDonald MR. 1993. New onset wheezing in an older male population: evidence of allergen sensitization in a longitudinal study. Results of the normative aging study. J. Allergy Clin. Immunol. 91:752-57 Ohman JL, Findlay SR, Leiterman KM. 1984. Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of in vivo and in vitro responses. J. Allergy Clin. Immunol. 14:23&39 Deleted in proof Parish LC, Schwartzman RM. 1993. Zoonoses of dermatologic interest. Semin. Dermatol. 12:5744 Patterson R. 1987. Diagnosis of animal allergy. N. Engl. Reg. Allergy Proc. 8: 167-68 Peter G, ed. 1994. Red Book: Report of the Committee of Infectious Diseases. Elk Grove, 1L: Am. Acad. Pediatr. 23rd ed. Platts-Mills TAE. 1993. Allergen-specific treatment for Asthma: 111. Am. Rev. Respir. Dis. 148553-55

244 GOLDSTEIN ET AL 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. Platts-Mills TAE, Chapman MD, Squillace SP, Sporik RB, Call RS, Heymann PW. 1993. The role of allergens. In Asthma: Physiology, Immunopharmacology and Treatment, 4th. Int. Sytnp.. pp. 27-39. New York Academic Platts-Mills TAE, Sporik RB, Wheatley LM, Heymann PW. 1995. Is there a dose-response relationship between exposure to indoor allergens and symp toms of asthma? J. Allergy Clin. Immunol. 96435-40 Plaut M, Zimmerman EM. 1993. Allergy and mechanisms of hypersensitivity. In Fundutnental Immunology, ed. WE Paul, pp. 1399425. New York, Raven. 3rd ed. Pollart SM, Chapman MD, Fiocco GP, Rose G, Platts-Mills TAE. 1989. Epidemiology of acute asthma: IgE antibodies to common inhalant allergens as a risk factor for emergency room visits. J. Allergy Clin. Immunol. 83:875-82 Reed KD, Moore FM, Geiger GE, Stemper ME. 1993. Zoonotic transmission of sporotrichosis: case report and review. Clin. Itfect. Dis. 16:384-87 Reynolds SP, Jones KP, Edwards JH, Davies BH. 1993. Inhalation challenge in pigeon breeder s disease: BAL fluid changes after 6 hours. Eur. Respir. J. 6467-76 Rodriguez de Castro F, Carrillo T, Castillo R, Blanco C, Diaz F, et a]. 1993. Relationships between characteristics of exposure to pigeon antigen. Chest 1031059-63 Saeed AM, Harris NV, DiGiacomo RF. 1993. The role of exposure to animals in the etiology of Cumplyobacter jejunikoli enteritis. Am. J. Epidemiol. 137: 108-14 Schad GA. 1994. Hookworms: pets to humans. Ann. Intern. Med. 120:434-35 Schlossberg D, Delgado J, Moore M, Wishner A, Mohn J. 1993. An epidemic of avian and human psittacosis. Arch. Intern. Med. 153:2594-96 Schwartz BS, Goldstein MD, Childs JE. 1994. Longitudinal study of Borrelia burgdorferi infection in New Jersey outdoor workers, 1988-1991. Am. J. Epidemiol. 139504-12 Sears MR, Hervison GP, Holdaway MD, Hewitt CJ, Flannery EM, Silva PA. 1989. The relative risks of sensitivity to grass pollen, house dust mite, and cat dander in the development of childhood asthma. Clin. Exp. Allergy 19:419-24 Shaw R, Woodman K, Crane J, 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. Moyes C, Kennedy J, Pearce N. 1994. Risk factors for asthma symp toms in Kawerau children. NZ Med. J. 107~387-91 Siraganian RP. 1987. Allergy to animals: principles of clinical management. N. Engl. Reg. Allergy Proc. 8: 181-83 Slavin RG. 1987. Clinical aspects of allergies to animals: overview and definition. N. Engl. Reg. Allergy Proc. 8: 163-66 Smith RP Jr, Rand PW, Lacombe EH, Telford SR 111, Rich SM, et al. 1993. Norway rats as reservoir hosts for Lyme disease spirochetes on Monhegan Island, Maine. J. Infect. Dis. 168: 687-91 Sporik R, Ingram JM, Price W, Sussman JH, Honsinger RW, Platts-Mills TA. 1995. Association of asthma with serum IgE and skin test reactivity to allergens among children living at high altitude. Tickling the dragon s breath. Am. J. Respir. Crit. Care Med. 151: 1388-92 Tauer-Reich I, Fruhmann G, Czuppon AB, Baur X. 1994. Allergens causing bird fancier s asthma. Allergy 49:448-53 Deleted in proof Todd A, Coan R, Allen A. 1993. Pigeon breeders lung; IgG subclasses to pigeon intestinal mucin and IgA antigens. Clin. Exp. Immunol. 92:494-99 Tompkins LS. 1994. Rochalimaea infections: are they zoonoses? JAMA 271: 553-54 Van Metre TE Jr, Marsh DG, Adkinson NF Jr, Fish JE, Kagey-Sobotka A, et al. 1986. Dose of cat (Felis domesticur) allergen 1 (Fel d I) that induces asthma. J. Allergy Clin. Immunol. 78: 62-75 Van Metre TE Jr, Marsh DG, Adkinson NF Jr, Kagey-Sobotka A, Khattignavong A, et al. 1988. Immunotherapy for cat asthma. J. Allergy Clin. Immunol. 82:1055-68 Van Toorenenbergen AW, Van Wijk RG, Van Dooremalen G, Dieges PH. 1985. Immunoglobulin E antibodies against budgerigar and canary feathers. In:. Arch. Allergy Appl. Immunol. 77: 433-37 Warner JA, Marchant JL, Warner JO. 1993. Allergen avoidance in the homes of atopic asthmatic children: the effect of Allersearch DMS. Clin. Exp. Allergy 23 : 279-86 Wood RA, Eggleston PA. 1995. The Effects of intranasal steroids on nasal and pulmonary responses to cat expo-

Annual Reviews HEALTH HAZARDS OF PETS 245 sure. Am. J. Respir. Crit. Care Med. I5 I :3 I 5-20 86. Wood RA, Mudd KE, Eggleston PA. 1992. The distribution of cat and dust mite allergens on wall surfaces. J. Allergy Clin. Immunol. 89: 126-30 87. Zangwill KM, Hamilton DH, Perkins BA, Regnery RL, Plikaytis BD, Hadler JL, et al. 1993. Cat scratch disease in Connecticut. Epidemiology, risk factors, and evaluation of a new diagnostic test. N. Engl. J. Med. 329:8-13