Zoonoses are diseases that can be transmitted from animals to humans. They can be acquired via insect vectors, food, and direct or indirect contact with animals. More than 250 zoonoses have been described, and they are caused by a wide variety of pathogens,including viruses, rickettsia, bacteria, fungi, and parasites. Some of the diseases are rare, such as rabies and plague; others, such as cat-scratch disease, are common. The transmission of zoonotic diseases is both diverse and dynamic. Although illnesses such as salmonellosis and campylobacteriosis are by far the most common zoonotic infections in humans and are transmitted most often by food, there is a small risk of acquiring illness from pets and wildlife.Because many pet- and wildlife-related zoonoses are acquired via fecal-oral or direct contact routes, the inquisitive nature of children puts them at a higher risk for infection than adolescents and adults. It is important for pediatricians to be aware of zoonoses, especially those related to direct pet contact, because approximately 56% of United States households contain at least one pet. Pet ownership has many psychological and social benefits and should not be discouraged,with the exception of households that contain immunocompromised individuals or children younger than age 5 years, which should not have reptiles because of the risk of salmonellosis.This review discusses the epidemiology, animal reservoirs,transmission, clinical syndromes, laboratory features, treatment, and prevention of toxoplasmosis, rabies, cat-scratch disease, Lyme disease,and rat-bite fever. Additionally, brief overviews of animal bites and enteric infections are presented, as are tables on zoonoses related to dogs, cats, rodents, birds, and exotic pets (Table 1); animal bite-related zoonoses (Table 2); and vector-borne diseases (Table 3). Toxoplasmosis has a worldwide distribution. The seroprevalence in women of childbearing age in the United States is approximately 15%,but it is more than 50% in populations in much of western Europe,Africa, and Central/South America. The frequency of congenital infection in the United States is not known but has been estimated at 1 per 1,000 to 10,000 births. The frequency of serious disease in older children and adults is related to immunosuppression and especially human immunodeficiency virus(HIV) infection. The etiologic agent is Toxoplasma gondii, an intracellular eukaryotic parasite.Cats are the only host in which T gondii undergoes a complete reproductive cycle. Other animals,including humans, are incidental or“dead-end” hosts. Large numbers of oocytes are shed in cat feces after primary infection and contaminate soil that then serves as a reservoir of infection because the eggs survive for prolonged periods.Human infection can be acquired via ingestion of Toxoplasma cysts in undercooked meat and by direct contact with oocytes through gardening or indirectly via food contaminated with cat feces. Human infection is most common in areas where consumption of raw or lightly cooked meat is typical or where there is environmental contact with cat feces. T gondii can be transmitted from mother to fetus when healthy pregnant women become infected for the first time or when infection is reactivated in immunocompromised pregnant women. The rate of transmission and severity of congenital infection are inversely related; infection early in pregnancy is associated with a more severe outcome in the fetus, but the rate of congenital transmission is highest in the third trimester. Other rare modes of transmission include blood/blood product transfusion, bone marrow/organ transplantation, and laboratory accident.Congenital infection acquired during the first 6 months of gestation typically causes signs and symptoms in the neonatal period, including microcephaly, hydrocephalus, seizures, and chorioretinitis. Hepatosplenomegaly and hyperbilirubinemia also can occur. Although infection transmitted in the third trimester does not cause symptoms at birth, chorioretinitis or central nervous system complications may occur later. Acute infection in healthy older children and adults most often is asymptomatic or nonspecific, but lymphadenopathy,fever, and flu-like symptoms can occur. Acute or reactivated infection in immunocompromised older children or adults can affect any organ system. The central nervous system is affected most commonly in patients who have acquired immunodeficiency syndrome (AIDS).A number of different serologic tests are available for diagnosis. In immunocompetent older children and adults, a fourfold rise in immunoglobulin G (IgG) titer over a 3-week interval in specimens tested simultaneously is adequate if a specific diagnosis is required. Diagnosis in immunocompromised hosts may require histologic demonstration of organisms in tissue or detection of T gondii nucleic acid by polymerase chain reaction (PCR). Suspected cases of congenital infection are diagnosed prenatally by culture or PCR-based detection of T gondiifrom amniotic fluid or umbilical blood. Postnatally, the placental blood, peripheral blood, and cerebrospinal fluid (CSF) can be analyzed by the same techniques to detect T gondii. IgG, IgM, and IgA tests on infant sera at birth also can be used to confirm the diagnosis. Because the diagnosis of congenital toxoplasmosis can have serious prognostic and theraputic implications, serologic testing should be performed by a reliable reference laboratory in consultation with clinical experts. Evaluation of the newborn who has suspected infection should include a head computed tomographic (CT) scan, CSF evaluation, and ophthalmologic examination.It is important to note that testing cats for T gondii is not useful. Additionally, the United States Food and Drug Administration (FDA) does not recommend the use of Toxoplasma IgM from commercial laboratories in pregnant women.Infection beyond the newborn period in otherwise healthy hosts is usually self-limited. Treatment of infants who have congenital toxoplasmosis and of older individuals who have chorioretinitis, other organ involvement, or immunocompromising conditions includes pyrimethamine,sulfadiazine, and leukovorin. Corticosteroids are used in the treatment of chorioretinitis and infant encephalitis.Gloves should be worn for gardening and cleaning the cat litter box. Inadequately cooked meat should be avoided by pregnant women and those who have compromised immune systems. Treatment of pregnant women who have acute infection with spiramycin (still considered an investigational drug that needs to be obtained from the FDA)can reduce the rate of congenital infection.The recent textbook chapter on toxoplasmosis in Principals and Practice of Pediatric Infectious Diseases (Long, Pickering, Prober 1997) provides a comprehensive overview of this topic.Rabies is rare in the United States;an average of three cases annually have been reported since 1990. It is far more common in the developing world, with approximately 35,000 cases occurring worldwide each year. The 32 cases reported in the United States from 1980 to 1996 occurred in 20 different states, led by California (7) and Texas (6). Patient ages ranged from 4 to 82 years (median, 27 y), 63% were male, and 11 people were exposed outside of the United States.Rabies is caused by a bullet-shaped virus, Lyssavirus type 1. It is a negative strand RNA virus that has an approximately 12,000 nucleotide genome.Of the cases reported in the United States since 1990, 74% have been caused by bat-associated rabies variants. The majority of the remainder was caused by rabies variants found in dogs outside of the United States. In addition to bats, important animal reservoirs in the United States are skunks and raccoons. In other countries, dogs remain the most important vectors, although numerous wild animals (mongooses, wolves, foxes,jackals, hyenas, bats) and occasionally other domestic animals and livestock have been implicated in transmission.Contrary to popular belief, not all rabid animals are aggressive and foam at the mouth. Animals that have rabies have a variety of clinical presentations, including increased affection toward people and lethargy.Rabies can be spread from the saliva of infected animals via bites or scratches. Transmission of rabies through the mucosa is less likely. Spread from human saliva is theoretically possible, but it has not been documented. Rabies has been spread from human to human, however, by cornea transplantation.Rabies encephalitis can begin with fever, malaise, headache, and anxiety. Sensory changes occur in the area of initial viral inoculation. A relentless progression of neurologic symptoms follows, including muscle spasm, autonomic instability,hallucinations, respiratory muscle paralysis, and coma plus increases in lacrimation, perspiration, and salivation.In the first week of illness, 60% of patients have elevated CSF white blood cell counts (mean, 7.0 109/L [70,000/mcL]). CSF glucose and protein concentrations usually are normal. Specific diagnostic tests(serology, direct fluorescent antibody, PCR) in suspected cases should be coordinated promptly with local public health officials to facilitate rapid testing of serum, saliva,CSF, and nuchal skin biopsy specimens.Rabies nearly always is fatal, despite supportive care. There is no known effective treatment. Public health authorities should be notified when a case is suspected to prevent further exposures.Domestic animal vaccination is very effective in preventing disease in those animals most likely to have contact with humans. Oral immunization of wildlife reservoirs is theoretically possible. Bite wounds should be cleansed thoroughly and promptly. Postexposure prophylaxis should be individualized in consultation with local public health authorities. Both passive immunization with rabies immune globulin and active immunization with human diploid cell vaccine are appropriate following exposure.Cat-scratch disease (CSD) is seen frequently in clinical practice, but because it is not a notifiable disease,accurate surveillance statistics are not available. A survey in Connecticut from 1992 to 1993 found an overall incidence of 3.7 cases/100,000 per year, with the peak incidence occurring in children younger than 10 years of age(9.3/100,000 per year). In this survey,52% of patients were female, 11%required hospitalization, and there were no deaths. An analysis of United States outpatient clinic visits led to an estimate of 24,000 cases annually. The vast majority of CSD is caused by a rickettsia-like organism known as Bartonella henselae.Approximately 90% of CSD patients have a history of cat contact. There are anecdotal cases of CSD associated with dog, rabbit, and monkey contact.Although B henselae bacteremia occasionally has been noted in older cats, kittens and younger cats are more likely to have B henselaeinfection and to transmit the organism. Cat-to-cat spread may occur primarily through cat fleas.Most patients who have CSD have a history of either close contact with or being bitten or scratched by a cat. CSD transmission can occur if saliva from a cat contacts an open wound on a human (eg, if a cat licks an open wound). The rate of transmission from a single encounter is not known. Transmission indirectly via cat fleas may play a minor role.In uncomplicated CSD, a nontender papule develops at the site of inoculation, followed by regional adenopathy that develops 1 to 2 weeks later. Regional nodes continue to enlarge for 2 to 3 weeks, then recede over the next 1 to 2 months. Nodes may be small and asymptomatic or become massively enlarged and last several months. They may suppurate late in the course,requiring needle aspiration for relief. Fever occurs in approximately 50%of symptomatic patients; systemic symptoms such as malaise, anorexia,and headache also can be present. The most commonly enlarged nodes are axillary (45%),cervical/submandibular (26%), and groin (18%).Many atypical manifestions of CSD are possible with or without regional adenopathy. Granulomatous hepatitis can come to medical attention as fever of unknown origin associated with abdominal pain and weight loss. An abdominal CT scan reveals multiple low-attenuation lesions of the liver, spleen, and kidney. Parinaud oculoglandular syndrome (POGS) consists of a conjunctival nodule, conjunctivitis, and ipsilateral preauricular adenopathy. The differential diagnosis of POGS includes other infections, but B henselae appears to be the major cause. In two large surveys of CSD,POGS was the clinical manifestation in 4% to 6% of cases.The most common neurologic complication of CSD is acute encephalopathy, which occurs in 0.3% to 2.0% of cases. Cranial and peripheral nerve dysfunction,myelitis, radiculitis, and cerebellar ataxia also have been reported. CSD encephalopathy can begin days to months after the onset of adenopathy and may include coma, seizures,and combative behavior. Results of CSF examination are normal or show mild pleocytosis and elevated protein. In general, brain imaging is nondiagnostic. The vast majority of patients recover completely, usually within 3 months.A distinctive neuroretinitis known as stellate macular retinopathy or Leber idiopathic stellate neuroretinitis most often is related to CSD, but other manifestions of CSD may be absent, making the diagnosis challenging. In this presentation, patients complain of painless unilateral loss of vision, and fundoscopic examination shows optic disc swelling and a radiating macular star. Recovery is usually complete in 1 to 3 months.Pneumonia, endocarditis, and osteomyelitis occur, but only rarely. Patients who have AIDS can develop a distinctive cutaneous vasoproliferative syndrome associated with B henselae infection known as bacillary angiomatosis and a visceral syndrome known as bacillary peliosis that affects the liver,spleen, and bone marrow.Typical cases of CSD lack distinctive laboratory features. Histopathologic examination of excised nodes demonstrates granulomas with necrosis and stellate microabscesses. Small pleomorphic bacilli can be demonstrated in excised tissue by using the Warthin-Starry silver stain in some cases. Serologic testing using either indirect immunofluorescence or enzyme immunoassay methods is available, but false-positive and false-negative findings have been reported. Serologic surveys demonstrate that approximately 5% of random blood donors have evidence of previous CSD. A positive serologic test result can help confirm the diagnosis in a child who has adenopathy, often eliminating the need for biopsy of a persistently enlarged node. Negative results in any age group may reflect poor sensitivity, and positive results in older individuals who have prolonged cat exposure may represent previous infection.Most cases of CSD regional adenitis, encephalopathy, POGS, and retinitis resolve without specific treatment. In vitro antimicrobial susceptibility data do not correlate with clinical response and have not been helpful in guiding therapy. In a retrospective survey, rifampin,ciprofloxacin, gentamicin, and trimethoprim/sulfamethoxazole appeared to produce a clinical response. More recently, macrolides have been used, based on the response of AIDS patients suffering from bacillary angiomatosis caused by the same organism. At this time,data are insufficient to support routine antimicrobial treatment of this self-limited adenitis in immunocompetent hosts. Discomfort from fluctuant nodes late in the course of CSD adenitis may be relieved by needle aspiration.Cat contact is usually required for transmission of CSD, but because most cases have a benign course,avoidance of cats is unwarranted. Immunocompromised patients will want to control cat fleas and may wish to limit their exposure to kittens and stray cats, which tend to carry B henselae more frequently than do older domestic cats.More than 12,000 cases of Lyme disease were reported in the United States in 1997. Most occurred in the summer and fall, and 83% were reported from Connecticut, New York, and Pennsylvania, although cases have been reported from all states. The highest rate of infection(6.29/100,000 per year) occurred in the 5- to 14-year-old age group. Males accounted for 53% of cases. The etiology is the spirochete Borrelia burgdorferi.B burgdorferi is transmitted to humans after bites from nymph or adult ticks. Ixodes scapularis (deer tick) is the most important vector in the northeast and midwest compared with Ixodes pacificus (black legged tick) in the west. Because transovarial transmission in the ticks is rare, the white footed mouse and the white tailed deer, which carry the organism, are essential reservoirs for continued transmission.Ticks at any stage (larva, nymph,adult) can transmit infection to humans, but nymphs are probably the most important vector because they are small, hard to detect, and abundant when people are likely to be outside. In general, the tick must be attached for approximately 1 day before transmission is possibleUp to 50% of those who recently have acquired Lyme disease may be asymptomatic. Three stages of symptomatic illness are recognized. In early localized Lyme disease, an annular rash, erythema chronicum migrans, gradually develops around a tick bite 1 to 2 weeks after the bite. This slowly expands to an average of 15 cm in diameter. Although classically it shows central clearing, the rash may be uniformly erythematous or develop a vesicular or necrotic center. The rash lasts for at least 1 to 2 weeks and resolves spontaneously. Systemic symptoms such as fever, fatigue, and myalgia may occur at this stage.In early disseminated Lyme disease, multiple, smaller, secondary erythema chronicum migrans lesions appear at sites distant from the original rash/tick bite. At this stage,systemic symptoms, conjunctivitis,aseptic meningitis, carditis (heart block), and focal neurologic involvement can occur.Arthritis is the manifestation of late disseminated Lyme disease in approximately 7% of untreated children. This typically occurs months after the original rash appears. Large joints, especially the knee, most commonly are involved. If untreated, joint swelling will resolve over a course of weeks, only to recur in the same or other joints. Over time, the frequency of recurrences diminishes. If treated, joint swelling resolves, but 5% to 10%patients may have recurrent arthritis.Routine laboratory studies are nonspecific in Lyme disease. The erythrocyte sedimentaion rate is usually elevated. Joint fluid analysis demonstrates 15,000 to 125,000/mm3 cells,primarily neutrophils. CSF analysis in those who have aseptic meningitis, erythema chronicum migrans, or cranial nerve palsies shows elevation of white blood cell count to 200 109/L (200,000/mcL), elevated protein, and normal glucose concentrations. Although B burgdorferi can be cultured, stained, and detected by PCR analysis, none of these tests is widely available and rarely are they needed. Serologic testing can be helpful in selected cases when the diagnosis must be clarified. Currently, a two-test approach, an enzyme-linked immunosorbent assay(ELISA) followed by a Western blot, is recommended. Because IgM antibodies appear 3 to 4 weeks after infection and IgG antibodies 4 to 8 weeks after infection, those who have early localized disease may have negative test results. Because IgG antibodies may persist indefinitely, even after treatment, serology is not helpful in previously seropositive patients. False-positive ELISA results have been associated with other spirochetal or viral infections and autoimmune diseases, and strict criteria for interpretation of Western blot tests have been developed.Recommendations for treatment of children are extrapolated from results in adults. Erythema chronicum migrans or early disseminated disease is treated for 21 days with amoxicillin, doxycycline,cefuroxime, or erythromycin. If there is cranial nerve involvement or arthritis, treatment is extended to 30 days. If there is carditis, meningitis,neurologic disease, or unresolved arthritis, parenteral ceftriaxone or penicillin G is recommended for 14 to 21 days. Prophylactic treatment for asymptomatic tick bites is not recommended.Ticks commonly attach to humans in shaded, grassy, and forested areas. Long pants tucked into socks,insect repellents, and checking for and removing ticks help prevent infection. Two vaccines have been tested recently, and one has been licensed and is recommended for those ages 15 years and older at high risk for acquiring Lyme disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP) are published in the Morbidity and Mortality Weekly Report. Vol 48, No RR07;1 06/04/1999.Rat-bite fever is not a nationally notifiable disease, and accurate surveillance statistics are not available. Rats are becoming popular pets, and most children’s hospitals encounter cases of rat-bite fever each year. It occurs worldwide and is caused by Streptobacillus moniliformis, an unusual gram-negative, pleomorphic,beaded rod. In Asia, rats can transmit Spirillum minus, a“spirillum-like” organism that has not been cultured and is reported to cause a similar syndrome. This discussion will be limited to disease caused by S moniliformis.S moniliformis is normal oral flora in wild, pet, and laboratory rats that can be excreted in rat urine. Mice,squirrels, cats, and weasels also can carry this organism.Humans usually are infected after a bite from a rat. Less commonly,infection is acquired after being scratched or by handling dead rats. The rate of transmission after a bite is not known. S moniliformis also can be acquired by ingestion of food or water contaminated by rat excreta.Approximately 3 to 10 days after inoculation or ingestion, there is abrupt onset of fever, chills,headache, myalgia, and rash. The rash may develop 2 to 4 days after the onset of fever and is usually maculopapular; often includes palms and soles; and may evolve into petechiae, purpura, vesicles, or desquamation. Approximately 50% of patients develop an asymmetric septic polyarthritis. Rare complications include endocarditis, pericarditis,and abscesses of soft-tissue and brain. Gastrointestinal and respiratory symptoms are more common when the organism is acquired through ingestion of food or water.The peripheral white blood cell count can be normal or elevated. Results of the rapid plasma reagin/venereal disease research laboratories (RPR/VDRL) tests can be false-positive. S moniliformis can be cultured from blood, joint fluid, or vesicles. The microbiology laboratory needs to be aware that this organism is being sought to optimize culture conditions.Penicillin G is the treatment of choice. Alternatives are ampicillin,cefuroxime, cefotaxime, and doxycycline. With treatment, complete recovery is the rule. In the preantibiotic era, mortality was reported to be 13%.Dwellings and play areas should be rodent-free. Pet rats pose a risk of uncertain magnitude, but there is not sufficient evidence to prohibit them as pets.See Table 2 for illnesses associated with pet and wildlife bites that are not described herein.Of the 1 to 2 million animal bite wounds that are estimated to occur in the United States each year, the majority are minor and require no medical care. Nonetheless,approximately 300,000 emergency department visits per year are prompted by animal bites, mostly from dogs or cats. Of these, cat bites appear to become infected more frequently. A recent microbiologic study of dog and cat bites revealed that most infected bite wounds harbor multiple organisms, led by Pasteurella sp. Frequently isolated aerobic organisms included streptococci,staphylococci, Moraxella, and Neisseria sp,and the most common anaerobes were Fusobacterium, Bacteroides,Porphyromonas, and Prevotella sp.Infected bite wounds are characterized by swelling, erythema, and warmth at the site of injury. Purulent drainage, abscess formation,fever, regional adenitis, and an elevated white blood cell count may be seen. Infections in which Pasteurellasp play a role often become symptomatic within 1 day and may spread rapidly. If fever is present in an immunocompromised patient after a dog or cat bite, systemic infection with Capnocytophaga canismorsis is possible. Rabies should be considered in all animal bites,and local health department officials should be contacted if necessary for advice on animal disposition and the need for postexposure prophylaxis.Aerobic and anaerobic cultures may be helpful in optimizing antibiotic therapy in bite wound patients who fail to respond to empiric therapy. Most infected bite wounds are polymicrobial, and broad-spectrum therapy is required.All patients should be evaluated and treated for any life-threatening problems. Subsequently, wounds should be explored carefully to document their depth and extent. Irrigation of wounds under pressure and debridement helps to decrease the chance of infection developing. The decision to close lacerations from bites must be made on a case-by-case basis,based on the location of the bite, the time since the bite, and any evidence suggestive of infection. When bite wounds are suspected to be infected, empiric antibiotics that are effective against Pasteurella sp,staphylococci, streptococci, and anaerobes should be administered. Common choices include amoxicillin/clavulanate or clindamycin plus trimethoprim/sulfamethoxazole (for patients allergic to penicillin).Although a complete discussion of enteric infections is beyond the scope of this review, several points related to animal-associated infection are relevant. Among pets,reptiles (turtles, iguanas, snakes)frequently carry Salmonella sp, and transmission to children is well documented even without direct contact. Because reptiles are asymptomatic,chronic, intermittent shedders of Salmonella sp, no reptile can be considered “Salmonella-free.” Public health authorities recommend that homes in which there are children younger than age 5, who are most susceptible to invasive disease, not keep reptiles. Although other household pets may become ill with Salmonella and Campylobacter,transmission from pets to humans is rare compared with person-to-person and food-borne spread. Similarly, there are animal reservoirs of Giardia and Cryptosporidium that may contaminate surface water and cause human disease, but the majority of infections in children are related to person-to-person spread, especially in child care settings.