Zoonotic Infections

October 1, 2008

A zoonosis is any disease-bacterial, mycotic, viral, or parasitic-that is transmissible from an animal to a human. More than 200 zoonoses have been identified. The newly emerging zoonosis that has achieved star status in the medical press is avian influenza. Another emerging threat is Nipah virus, which is transmitted from pigs to humans in the agricultural setting and causes encephalitis. But animal to human transmission of zoonoses are multimodal: from exposure to animal secretions in the agricultural setting, to transmission through insect vectors and ingestion of contaminated animal products, to more insidious routes, such as petting or being scratched or nipped at by one's pet dog, bird, cat, lizard, or other creature. A few interesting cases are presented here.

A zoonosis is any disease-bacterial, mycotic, viral, or parasitic-that is transmissible from an animal to a human. More than 200 zoonoses have been identified. The newly emerging zoonosis that has achieved star status in the medical press is avian influenza. Another emerging threat is Nipah virus, which is transmitted from pigs to humans in the agricultural setting and causes encephalitis. But animal to human transmission of zoonoses are multimodal: from exposure to animal secretions in the agricultural setting, to transmission through insect vectors and ingestion of contaminated animal products, to more insidious routes, such as petting or being scratched or nipped at by one's pet dog, bird, cat, lizard, or other creature. A few interesting cases are presented here.

Tularemia
An infected 3-cm laceration on the lateral aspect of the right leg of a 25-year-old construction worker (Figure 1) was accompanied by flu-like symptoms and a painful, right-sided inguinal lymph node. The patient only complained of fever and the enlarged node, which was 3 times its normal size and exquisitely tender. The lesion went unnoticed at the initial visit, during which the patient was uncooperative about examination procedures. He denied having symptoms of venereal disease or problems with his right leg or the right side of his body. Because he was uncooperative and refused further examination, he was given a single intramuscular injection of penicillin G benzathine, 1,200,000 U, and a prescription for double-strength trimethoprim/sulfamethoxazole (TMP/SMX).

Figure 1 -

This 3-cm laceration on the lateral aspect of the right leg ofa 25-year-old man was thought to be an entry site of Francisella tularensisvia exposure to the blood of an infected rabbit. (Case and photographsupplied by Neilson A. Smith, MD. Overview adapted fromRelman DA, Olson JE. Consultant. 2002;42:56.

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The patient returned the next day because the node had become more painful. His temperature was 38.4C (101.2F). During the visit, the examination was completed with the patient's cooperation. A second, smaller node in the same inguinal chain and the leg lesion were then discovered.

On questioning, it was learned that the patient had gone hunting the previous week and that he had sustained a cut on his leg sometime before then. During his hunting foray, he killed 2 jackrabbits and 2 cottontails. He placed them in a sack and tossed the sack over his shoulder. He later noticed that blood from the kill had leaked out of the sack and down his leg, seeping through a hole in his jeans and into the leg wound.

Tularemia, transmitted to the patient from a rabbit infected with Francisella tularensis, was suspected. The suspicion was confirmed by bacteriological identification from a biopsy of the node. On the recommendation of an epidemiologist, a 10-day course of streptomycin at a dosage of 1 g was given intramuscularly twice daily. Five days later, recurring fever mandated a second, 6-day course of the antibiotic. The patient was lost to follow-up.

F tularensis is a nonsporulating, nonmotile, aerobic gram-negative coccobacillus that is usually transmitted to humans from infected rabbits and other small animals via ticks, fleas, or deer flies or by direct contact. Infection was more commonly seen in the United States before World War II; the incidence then declined and in recent years has been between 0.05 and 0.15 cases per 100,000.

The incubation period averages 3 to 5 days but ranges from 1 to 21 days. The most common presentations are ulceroglandular and typhoidal diseases. The first type of presentation makes up 21% to 87% of cases in the United States and is the result of skin or mucosal inoculation. Patients present with localized enlargement and tenderness of lymph nodes and 1 or more painful ulcerative skin lesions as illustrated in this case. The second type of presentation results from aerosol exposure and is notable for fever, headache, prostration, cough, and substernal pain, without lymphadenopathy.

The diagnosis is usually made by serological methods (tube agglutination, microagglutination, and enzymelinked immunosorbent assay [ELISA]) several weeks after the onset of illness. The greatest impediment to a rapid diagnosis may be the lack of clinical suspicion in a patient with either primary pneumonia or typhoidal disease and no apparent traditional animal exposures. Streptomycin is the drug of choice and gentamicin is an effective alternative.1

Cystic echinococcosis
Echinococcosis is a zoonotic infection caused by the cestode species of the genus Echinococcus. Three species of Echinococcus cause hydatid disease in humans: Echinococcus granulosus, the most common variety, which causes cystic echinococcosis; Echinococcus multilocularis, which causes alveolar echinococcosis; and Echinococcus vogeli, which causes polycystic echinococcosis. Endemic foci are found in eastern, western, and southern Europe; the Middle East; North and South Africa; Australia; and New Zealand.

The adult tapeworms (3 to 6 mm long) inhabit the small intestine of carnivorous hosts, such as dogs, coyotes, and wolves. The cystic stage occurs in herbivorous intermediate hosts, such as sheep, cattle, goats, camels, pigs, and horses, and in humans.

In the typical dog-sheep cycle, dogs ingest viscera that contain echinococcal cysts with protoscolices (tiny tapeworm heads) inside. Protoscolices attach to dogs' intestines and develop into adult tapeworms capable of producing infective eggs. Tapeworm eggs are passed in the feces of an infected dog and may be ingested by grazing sheep. They hatch and migrate to specific sites where they develop into echinococcal cysts.

Humans, like sheep, become infected by ingesting tapeworm eggs either through direct contact or from food or water contaminated by fecal material that contains tapeworm eggs. Larvae migrate mainly to the liver (63%) and lungs (25%) and less frequently to the muscles (5%) and bones (3%).

Although echinococcosis is uncommon in the United States, transmission of E granulosus in the dog-sheep cycle occurs in the western states, principally California, Arizona, New Mexico, and Utah. In Arizona and New Mexico, echinococcosis is seen in American Indians who belong to the Zuni, Navajo, and Santo Domingo tribes. Members of these tribes generally live in close proximity to their animals.

The CT scan shows a large cystic lesion with multiple internal septations (Figure 2). It developed in an asymptomatic, healthy, 40-year-old woman who had hepatomegaly and reported having a sensation of fullness in the upper abdomen for many years. The woman had been raised on a farm in Greece and moved to the United States at age 24 years. Based on ultrasonography, CT, and laboratory test results and the patient's history (exposure to farm dogs or sheep dogs in areas where E granulosus is endemic), echinococcosis was suspected. Results of an indirect hemagglutination test and an ELISA were positive for IgG antibodies against Echinococcus.

Figure 2 -

The cause of hepatomegaly in a middle-aged woman was alarge cystic lesion with multiple internal septations as depicted in thisCT scan of the liver. The patient was asymptomatic but a history ofexposure to sheep in an agricultural setting sparked suspicions ofEchinococcus granulosus infection, confirmed by assay tests. (Caseand photograph supplied by Navin M. Amin, MD.)

Albendazole and mebendazole are the only anthelmintic agents effective against cystic echinococcus. Albendazole, which is more effective for liver cysts, is dosed at 400 mg bid for 6 to 12 months. Mebendazole is dosed at 10 mg/kg/d. Both agents are contraindicated in pregnancy. With drug treatment, cysts disappear in up to 30% of patients; in 30% to 50%, cysts degenerate or shrink significantly; and in 20% to 40%, cysts remain morphologically unchanged.

The treatment choices presented to the patient were surgery, percutaneous puncture of the cyst, and chemotherapy. The patient chose chemotherapy. Thus, a regimen of albendazole 400 mg bid was begun. After 6 months of therapy, an abdominal CT scan showed a 30% reduction in the size of the cyst. An additional 6 months of therapy with regular follow-up was recommended.

Unusual manifestation of brucellosis
Brucellosis is another zoonotic infection that occurs in persons who have direct contact with domestic animals. Historically, it was also spread by consuming unpasteurized milk and contaminated cheese. Clinical symptoms include intermittent fever, chills, headache, profound weakness, arthralgia, myalgias, and weight loss. This infection is associated with orchiditis and epididymitis in men and miscarriage in women.

The nonpruritic, nonhemorrhagic, maculopapular rash that had developed on the arms, legs, and trunk of a 49-year-old farmer is an unusual presentation of brucellosis (Figure 3). The patient was hospitalized because of a 3-week history of intermittent fever, fatigue, anorexia, generalized myalgias, and malodorous sweating. The reddish lesions of the rash were less than 1 cm in diameter. There was no history of antibiotic or antipyretic drug therapy, and no other abnormalities were found on physical examination.

Figure 3 -

This nonpruritic, nonhemorrhagic, maculopapular rash isan unusual presentation of brucellosis. It was accompanied by classicsymptoms of intermittent fever, fatigue, anorexia, and generalizedmyalgias. (Case and photograph supplied by Haralamos J. Milionis,MD, Leonidas Christou, MD, and Moses Elisaf, MD.)

Results of a complete blood cell count were normal except for a hematocrit value of 40% and a platelet count of 410,000/?L. The erythrocyte sedimentation rate was 35 mm/h. The patient's C-reactive protein level was 24 mg/dL, and the results of a rheumatoid factor test were negative. Biochemical parameters were normal except for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which were twice the upper normal limit.

An ECG, a chest film, and abdominal and transthoracic heart ultrasonograms showed no abnormalities. A tuberculin skin test yielded negative results, as did serological tests for syphilis, brucellosis, leptospirosis, rickettsiosis, mycoplasmosis, and toxoplasmosis, as well as for infection with Cytomegalovirus, Epstein-Barr virus, herpes simplex virus, HIV, and hepatitis C virus. The patient was immune to hepatitis B. Urinalysis results were normal, and urine and blood cultures were negative for pathogens.

Bone marrow for cultures was obtained on admission; the cultures were positive for Brucella melitensis, which is the strain found in sheep and goats. The patient was given doxycycline 200 mg/d and rifampin 900 mg/d for 6 weeks. The skin lesions disappeared a few days after therapy was initiated.

Cutaneous leishmaniasis
Cutaneous leishmaniasis was one of the souvenirs of a 6-week trip to the rain forests of Peru for a 28-year-old, female graduate student (Figure 4). The lesion began as a raised papule that enlarged over a 3-week period. It was nontender and did not itch. Lymphadenopathy was absent. A Giemsa-stained touch preparation of the skin consistent with leishmaniasis (Figure 5). Culture was thwarted by yeast overgrowth, but a companion of the patient also had the same kind of lesion; culture of a biopsy sample from that lesion revealed Leishmania braziliensis.

Figure 4 -

This erythematous, crusty lesion on the right shoulder ofa 28-year-old woman who had traveled to the tropics was nontenderand nonpruritic. The diagnosis: cutaneous leishmaniasis. (Case andphotograph supplied by Shelley A. Gilroy, MD, Deanna L. Kiska,PhD, Betty Ann Forbes, PhD, and William Shu, MD.)

Figure 5 -

A Giemsa-stained touch preparation of a biopsy samplefrom the lesion revealed Leishmania amastigotes (arrows). (Case andphotograph supplied by Shelley A. Gilroy, MD, Deanna L. Kiska,PhD, Betty Ann Forbes, PhD, and William Shu, MD.)

On the basis of these findings, a presumptive diagnosis of cutaneous L braziliensis infection was made. The patient was treated with 20 mg/kg/d of intravenous sodium stibogluconate for 20 days. She experienced myalgias and mild elevations in serum ALT, AST, amylase, and lipase levels, which normalized after cessation of therapy. After completion of therapy, the lesion decreased in size and scarred over.

Leishmania organisms are obligate intramacrophage protozoa. Numerous Old World and New World species exist, and areas of endemicity are the tropics and subtropics. Thus, patients presenting with leishmaniasis in the United States typically have a history of recent travel, although rare cases have been reported in Texas.2

Cutaneous leishmaniasis is transmitted by the bite of an infected female phlebotomine sandfly, which itself becomes infected by feeding on the blood of infected mammals, including humans. Leishmaniasis also can be transmitted congenitally and through parenteral exposure to infected blood (ie, blood transfusion or needle-sharing). Lesions can range from being small, dry, and crusted to being large, deep, disfiguring, and ulcerous. They may be single or multiple and usually develop on exposed areas of skin (eg, face, arms, and legs). Other symptoms may include regional lymphadenopathy, malaise, anorexia, weight loss, and low-grade fever.

Diagnosis is made on the basis of patient history and clinical presentation and is often confirmed by Giemsa staining of a skin biopsy specimen. Most cases resolve within several weeks to 3 years without treatment. Systemic treatment with sodium stibogluconate, available in the United Kingdom but an investigational drug in the United States and only available through the CDC, is indicated for infections caused by the L braziliensis species complex and is used to help prevent mucosal leishmaniasis and decrease morbidity associated with the chronicity of the skin lesion.

References:

  • Relman DA, Olson JE. Tularemia: a brief overview. Consultant. 2002;42:56.

  • Centers for Disease Control and Prevention. Fact sheet. Leishmania infection. www.cdc.gov/ncidod/dpd/parasites/leishmania/factsht_leishmania.htm# get_us. Accessed August 28, 2008.