When any child is evaluated for fever without an obvious etiology, one question to ask is whether this patient has pets or has been exposed to animals, particularly sick ones. The obvious implication is that animals carry many unique, communicable pathogens that might account for the current illness. The likelihood is great because there are more than 77.5 million dogs and 93.6 million cats living in US households. They are just two of a number of species of animals that cohabit with our patients.
These vast numbers greatly increase the likelihood that the animal is the source of a febrile illness. Wild animals also harbor organisms that are in their stool, urine, or secretions, indirectly exposing unsuspecting humans who enter the animal’s environment. In addition, exposure to dead animals can result in disease acquisition.
When a physician has identified that the cause of the fever is exposure to an animal, the parent should be advised as to practices to prevent further transmission, such as handwashing. If the cause of the fever is identified as something other than animal contact, the parent should still be advised as to risk prevention measures.
Many publications have discussed zoonoses by first identifying the animal and then elaborating on each disease that it can transmit to humans.1–6 This review is unique in that it begins with fever and the organ system involved and then suggests likely pathogens once animal contact is disclosed. The Tables are extensive, and every effort was made to make them complete; however, space limitations do not allow text discussion of all febrile zoonotic diseases for each organ system.
Skin and Skin Structure
Dogs and Cats
Bite injuries (see Table 1) constitute the greatest risk of contact with animals. Dogs are responsible for 80% to 90% of bites, and cats are responsible for 5% to 10% of bites. Approximately 30% of cat and 6% of dog bites result in cellulitis.1,7 Cat bites more commonly cause skin and skin structure infection because they produce puncture wounds that bury organisms deep in tissue, while dog bites cause tearing injuries that can be opened and irrigated, reducing the likelihood of cellulitis.
Table 1. Skin and Skin Structure Infection After Animal Bites or Direct Contact with Animals
The most common pathogen recovered from these infections is Pasteurella multocida, which is part of the oral flora of 70% to 90% of cats and 25% to 50% of dogs. Quite characteristic is that once exposed, the patient develops cellulitis in less than 24 hours with swelling, erythema, tenderness, regional lymphadenopathy, and a serous or sanguinopurulent discharge from the site. Fever occurs in 20% of infections, and is often accompanied by chills. Occasional local complications are septic arthritis, osteomyelitis, and tenosynovitis.
Other pathogens causing cellulitis and abscesses after dog and cat injuries are Capnocytophaga canimorsus,8Staphylococcus intermedius, and microaerophilic Streptococci. These organisms cause fever in more than 5% of cases.
Rat-bite fever is transmitted by bites, scratches, or exposure to oral, nasal, or conjunctival secretions, or urine from infected rodents and rodent-eating animals. Caused by either Streptobacillus moniliformis or Spirillum minus, this disease is increasingly reported because rats are now popular as pets among adolescents and preadolescents, possibly as a result of the Harry Potter book and movie series. (Children in these stories frequently have pet rats.) After an incubation period of 3 to 10 days, key symptoms of this illness are high fever, rash, and arthritis.9
Rat-bite fever begins with abrupt onset of fever, chills, myalgia, vomiting, headache, and occasionally adenopathy. The rash appears 1 to 3 days after the onset of fever and is most commonly maculopapular, although it can be petechial or pustular, and occurs predominantly on the extremities, including the palms and soles. Nonsuppurative and migratory polyarthritis or polyarthralgia follow the rash in 50% of cases.
If left untreated, it relapses in about 3 weeks. Complications include soft tissue and solid organ abscesses, pneumonia, endocarditis, myocarditis, parotitis, tenosynovitis, brain abscesses, and meningitis. The disease is severe and can be fatal in those younger than 3 months of age.
Cutaneous anthrax caused by Bacillus anthracis most commonly affects the skin but is also known to cause disease of the oropharynx, mediastinum, and intestinal tract.10 Infection is acquired though contact with herbivores (eg, goats, cattle, sheep, horses, and pigs), or with their carcasses, through abraded skin.
Cutaneous anthrax has an incubation of 1 week or less and begins as a pruritic papule or vesicle that enlarges and ulcerates in 1 to 2 days. In 2 to 6 days, a subsequent black eschar forms. This process is characteristically painless but may develop with surrounding edema, hyperemia, and regional adenopathy. Other common signs and symptoms are malaise and headache. Fever occurs in 10% of anthrax infections limited to the skin and soft tissue but in virtually all cases with dissemination.
Fish and Wild Game
Erysipeloid caused by either Erysipelothrix rhusiopathiae or E. insidiosa is attained though contamination of skin abrasions while handling infected materials from fish and wild game or occasionally from a bite.11
Signs and symptoms vary from a localized cutaneous eruption to a more severe generalized cutaneous form and/or septicemia. Development of septicemia is often associated with endocarditis. Incubation is 1 to 4 days, and lesions slowly progress to be purplish-red painful indurations. Fever, lymphadenitis, and other constitutional symptoms appear in less than 10% of infections limited to skin and skin structure. If left untreated, Erysipelothrix infection is a self-limiting illness that lasts an average of 3 weeks.
Sheep and Goats
Skin lesions in humans after direct contact with sheep, goats, and wild ungulates, and particularly with their young, is termed ecthyma contagiosum, or contagious ecthyma caused by the Orf virus. The virus can persist in the soil or on animal skins and hair for months. Incubation is 3 to 6 days, and illness presents with a low-grade fever that subsides within 3 to 4 days in 70% of cases. Lesions form 1 week after exposure and can last for up to 3 to 6 weeks.
The lesions are usually located on the hands, arms, or face at the point of contact. They appear as red to violaceous vesicles, nodules, or maculopapules, progressing to weeping nodules with central umbilication. Other signs and symptoms are regional adenitis and a truncal maculopapular rash. Erythema multiforme and erythema multiforme bullosum are rare manifestations of Orf, as are disseminated disease and serious ocular damage.
Reptiles’ mouths are actually quite clean, containing only non-virulent anaerobes, despite their common gastrointestinal colonization with Salmonella. Bites rarely result in cellulitis but do produce tissue trauma. If fever is present, other potential causes should be investigated.
Bites from these large animals are severe, and infection almost always produces fever. Their mouth flora is quite unusual, with the most common organisms recovered from human infection after bites being Aeromonas hydrophila, Proteus vulgaris, and Pseudomonas.12
Sheep and Animal Placentas
Q fever (Coxiella burnetii) presents as an acute febrile illness with lower respiratory tract symptoms, such as cough with chest pain, accompanied by fever in more than 90% of cases, sudden chills, retrobulbar headache, weakness, anorexia, malaise, and sweating (see Table 2, page 33). Bronchopneumonia is seen on chest X-rays, and abnormal liver function tests are common. With proper treatment, the pneumonia lasts 1 to 4 weeks then slowly resolves.
Table 2. Pneumonia After Contact with Animals
It is usually acquired through airborne transmission or direct contact with animals or their products, particularly animal placentas. A famous report of multiple individuals acquiring disease while playing poker as a cat delivered her kittens under their card table led to the naming of this disease “poker players’ pneumonia.”13 The frequent infection of sheep in Spain has resulted in Q fever being the most common documented cause of pneumonia in young adult males in that country.
Inhalation anthrax is referred to as woolsorter’s disease (also used to describe cutaneous infection) because it is most associated with sheep or their infected wool.10 A characteristic sign is the widening of the mediastinum on chest X-ray, a result of pulmonary inflammation and edema secondary to the organism’s toxin production. It has a long incubation period of up to 42 days with a prodrome of fever, sweats, non-productive cough, chest pain, headache, myalgia, malaise, nausea and vomiting.
Parrots and Parakeets
Psittacosis caused by Chlamydophila psittaci is an acute lower respiratory tract infection with fever in 80%, nonproductive cough, rash, chills, myalgia, headache, and malaise acquired by inhalation of infected bird excretions or contaminated dust. It is characterized by extensive interstitial pneumonia with radiographic changes that appear more severe than the physical findings would suggest. Incubation is 5 to 14 days but can be longer.
Cryptococcus neoformans pneumonia is attained through inhalation of soil contaminated with pigeon or other bird feces. It is often asymptomatic but in 80% of cases, symptoms present with fever along with cough, chest pain, and malaise. Occasionally producing a single solitary “coin” lesion on chest X-ray, Cryptococcus most frequently manifests as a diffuse infiltrate.
Melioidosis (Whitmore disease) and glanders, caused by Burkholderia pseudomallei and B. mallei, respectively, are saphrophytic organisms that live in soil and water but are frequently carried to their human contacts by various animals such as sheep, goats, horses, swine, monkeys, and rodents. P. pseudomallei cause fever and severe respiratory symptoms with lung consolidation, abscesses, or necrotizing pneumonia.
The illness may look like typhoid fever or tuberculosis with pulmonary cavitations, empyema, chronic abscesses, and osteomyelitis. The closely related organism, B. mallei, causes a highly communicable disease of horses, mules, and donkeys. Clinical glanders is no longer endemic in the Western Hemisphere, but there are rare, sporadic cases reported in patients who have had contact with animals.
Hamsters and Guinea Pigs
Lymphocytic choriomeningitis (see Table 3, page 34) is a rodent-transmitted virus that is excreted in their urine, saliva, blood, and feces. It is acquired by humans through oral or respiratory routes, contact with animal fluids, or through skin abrasions. The illness has a varied biphasic presentation.14
Table 3. Meningitis and Neurologic Diseases After Contact with Animals
Incubation period is 8 to 13 days, and symptoms include a flu-like illness with retro-orbital headache, photophobia, anorexia, nausea, leukopenia, and thrombocytopenia. The fever usually lasts 1 to 3 weeks. The initial course has a good prognosis. The second phase 15 to 21 days after an asymptomatic period occurs in up to half of patients. It presents with meningitis or meningoencephalomyelitis.
Other occasional signs and symptoms of this phase are orchitis, parotitis, arthritis, leukopenia, myocarditis, and rash. With CNS involvement, a CSF lymphocytic pleocytosis occurs with mild hypoglycorrhachia. Transplacental infections can occur, resulting in congenital infection similar to that of congenital toxoplasmosis.
B virus (Herpes simiae or cerocopithecine Herpesvirus 1) causes an ascending CNS infection, termed monkey B encephalitis, in those who have close contact with an infected Eastern Hemisphere monkey.
This rare but highly fatal disease is acquired through exposure of skin or mucous membranes to an infected monkey’s saliva. Incubation is 3 days to 3 weeks, and the illness starts as an acute febrile illness with headache, often local vesicular lesions, lymphocytic pleocytosis, and variable neurologic patterns. There is itching, pain, and/or numbness at the exposure site.
C. canimorsus is part of the oral bacterial normal flora of dogs and rarely cats and other mammals. Infection in humans occurs after a bite or scratch, and disease can be severe in individuals who are asplenic, chronic alcoholics, or who have chronic lung disease.8
More than half of these infected patients develop sepsis, a combination of septicemia and meningitis, or a fever of unknown origin. Incubation is 1 to 2 weeks. Signs and symptoms include fever, diarrhea, abdominal pain, vomiting, headache, confusion, disseminated intravascular coagulation, septicemia, meningitis, endocarditis, and, rarely, ocular infections.
Hendra virus, discovered in Australia in 1994, is acquired through direct oral or nasal contact with infected horses or their contaminated tissues.15 Incubation period is 4 to 18 days but can occasionally be several months.
The full spectrum and course of the illness is unknown, but it has been reported as being prolonged and initially starting as mild meningoencephalitis. Signs and symptoms range from mild acute fever, headaches, sore throat, dizziness, drowsiness, and disorientation to coma and death. Case fatality rate for clinical cases is 50%, and reactivation has been described.
Nipah virus, discovered in Malaysia in 1999, is acquired from swine and may cause encephalitis. Infection is through direct contact with infected animals or their contaminated tissues through oral and nasal routes.16 Incubation period ranges from 4 to 18 days but can occasionally take several months. The full spectrum and course of the illness is still unknown. Signs and symptoms vary from mild with acute fever, headaches, sore throat, dizziness, and drowsiness to severe with altered mental status, coma and death. Case fatality rate for clinical cases is 50%.
Bats, Wild Animals, and Dogs
Rabies is a viral encephalomyelitis with a gradual onset and is almost always lethal. Illness is preceded by fever, a sense of apprehension, headache, malaise, and sensory changes at the site of exposure. It progresses to paresis or paralysis, hydrophobia, delirium, and seizures.
Incubation period is highly variable (days to years) but averages 3 to 8 weeks. Duration of illness is typically 2 to 6 days, and death occurs from respiratory paralysis. It is transmitted through bites, or contact with the saliva, urine, or neural tissue of infected animals. Diagnosis is made by fluorescent antigen testing in brain tissue of the offending animal or with fluorescent microscopy of a skin biopsy from the nape of the neck of the patient. Other methods of diagnosis include viral isolation from saliva, antibody in the CSF or serum of nonimmunized persons, and by PCR.
Infection with Toxoplasma gondii (toxoplasmosis) in the immunocompetent host causes a benign, self-limited infection with the only common manifestation being cervical lymphadenopathy. In some patients, a mononucleosis-like illness may occur with fever, malaise, sore throat, myalgia, and lymphocytosis persisting for days to weeks. Twenty percent have fever.
Cysts remain after recovery (especially in the brain) and may reactivate causing CNS disease if the patient becomes immunosuppressed. Likewise, primary infection in immunodeficient patients may disseminate to the CNS with signs and symptoms similar to a CNS tumor. Primary infection in the pregnant woman may result in a congenital infection with hydrocephalus, calcifications of the brain, and chorioretinitis.
Cats are the only definitive host of T. gondii transmitting disease by the fecal-oral route (litter boxes) or in dust containing infected fecal or urine matter. Ingestion of undercooked meat is also a source. Incubation period is approximately 7 days, and the infective oocyte can live in soil for more than 1 year.
Additionally, P. multocida has been reported as the pathogen causing meningitis in children bitten by or exposed to cats.
Baylisascaris procyonis, the raccoon roundworm, causes acute eosinophilic meningoencephalitis when transmitted to humans. Signs and symptoms include fever, mental status changes, and seizures. The presence of peripheral and/or CSF eosinophilia is the unique laboratory finding.
Although subclinical or asymptomatic infection may be relatively common, in patients with neurologic changes, severe neurologic sequelae or death are the usual outcomes.
Eosinophilic meningitis caused by the rat lungworm, Angiostrongylus cantonensis, occurs after ingestion of parasitized snails and slugs. Although most cases have occurred in Hawaii, there have been reports from many other states.
According to the Centers for Disease Control and Prevention, some infected people don’t have any symptoms, or have only mild symptoms that don’t last very long. Sometimes the infection causes eosinophilic meningitis. The symptoms can include headache, stiff neck, tingling or painful feelings in the skin, low-grade fever, nausea, and vomiting.
Reptiles, Amphibians, and Almost All Other Animals
Virtually all animals are periodically colonized with one of the more than 2,500 species of Salmonella (see Table 4, page 35).17,18 Once transmitted to humans, the disease presents as an acute gastroenteritis with high fever; headache; nausea; vomiting; dehydration; diarrhea; abdominal cramping; bacteremia; and/or focal infection.
Table 4. Gastroenteritis After Contact with Animals
It can occasionally present asymptomatically or as a protracted illness with gradual onset of fever, constitutional symptoms, abdominal pain, hepatomegaly, splenomegaly, and changes in mental status. Exposure is most commonly oral-fecal or by direct contact with turtles, chickens, reptiles, dogs, cats, birds, hamsters, rodents, and livestock. Incubation is 12 to 36 hours. Complications include osteomyelitis, abscesses, pneumonia, pyoderma, pyelonephritis, septic arthritis, cholecystis, endocarditis, meningitis, and pericarditis.
Cats and Farm Animals
Campylobacter is acquired through fecal-oral routes most commonly from cats, swine, sheep, and cattle, particularly the younger animals. Symptoms include diarrhea, abdominal pain, malaise, nausea, vomiting, and fever. Most stool samples contain visible or occult blood. Infection can also mimic appendicitis, intussusception, or acute inflammatory bowel disease.
In neonates, bloody diarrhea without fever can be the only sign of infection. Incubation is 2 to 5 days but can be longer, and symptoms typically last about 1 week. Complications of infection include Guillain-Barré syndrome, reactive arthritis, Reiter’s syndrome, erythema nodosum, a typhoid-like illness, febrile convulsions, septicemia, and meningitis.
Cryptosporidium parvum illness is a consequence of fecal-oral spread,19 a potential culprit at petting zoos. Infections are also associated with cattle, rodents, cats, dogs, fish, sheep, birds, and reptiles. It causes non-bloody diarrhea with anorexia and vomiting. The vomiting is particularly common in young children. Symptoms wax and wane and include cramps, fatigue, and weight loss. The illness is self-limited, lasting 1 to 20 days. Incubation period is 2 to 14 days.
Dogs and Rats
Leptospirosis is an acute febrile illness with a varied presentation that is most frequently considered when patients are icteric and have laboratory evidence of hepatitis with direct (conjugated) hyperbilirubinemia and mild elevation of liver enzymes in serum. It can be acquired from a range of animals, mostly dogs, but also livestock, and contact with rat urine.
Anicteric disease is usually self-limited, presenting as relapsing fever or biphasic illness. Acute septicemia is characterized by conjunctival suffusion without purulent discharge and myalgia of the calf and lumbar regions. This phase includes fever in 80%, chills, headache, nausea, vomiting and transient rash all lasting 1 week. There may be an asymptomatic period lasting 3 to 4 days. The second phase is immune-mediated, consisting of fever; aseptic meningitis; conjunctival suffusion; uveitis; muscle tenderness; adenopathy; and a purpuric rash. This phase can last 1 week to several months.
Rabbits and Squirrels
Cleaning rabbits, eating them undercooked, and squirrel bites, in addition to tick bites, are all epidemiologic mechanisms for developing tularemia, caused by Francisella tularensis (see Table 5, page 36).20
Table 5. Lymphadenitis After Contact with Animals
Incubation period is 3 to 5 days. The abrupt onset of fever with adenitis, conjunctivitis with tender preauricular nodes (Parinaud’s oculoglandular syndrome) and adenitis proximal to the site of a squirrel bite are characteristic. Other clinical manifestations are chills, fatigue, myalgia, and headache.
Brucellosis (caused by Brucella abortus, B. melitensis, B. suis, or B. canis) is acquired through contact with infected animals, their carcasses, or their secretions. The illness may be acute or insidious, presenting with acute, intermittent, or prolonged fever (fever of unknown origin) and adenopathy. Infection may also relapse.