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1070 SECTION 13: Infectious Diseases children, and patients with travel to areas with fluoroquinolone-resistant Campylobacter (Thailand).11 Antimotility agents can be given to adults without signs of invasive bacterial infection (bloody stools or fever). 16 Probiotics, such as lactobacilli, may shorten the duration of diarrheal illnesses in adults and children. Metronidazole is a common first-line treatment for infections from Giardia and Entamoeba. However, tinidazole is more effective and better tolerated for Giardia treatment56 (Table 160-5). Parenteral metronidazole is still used initially for invasive disease from Entamoeba. Paromomycin is an alternative to metronidazole and tinidazole in pregnant women. 57 Other alternatives for Giardia and Entamoeba treatment include nitazoxanide and furazolidone. 57 Albendazole is also effective for giardiasis, but not amebiasis. Infections from Cryptosporidium are generally self-limited and usually do not require specific treatment in immunocompetent patients. However, use nitazoxanide or paromomycin in patients with prolonged infections, children, and the immunocompromised. 58 For immunocompromised patients with Cryptosporidium, nitazoxanide or paromomycin alone or in combination with azithromycin is used. Initiation of highly active antiretroviral therapy is the first priority for Cryptosporidium treatment in patients with HIV . 59 Treatment of meningoencephalitis from Naegleria fowleri includes amphotericin B (including intrathecal), rifampin, fluconazole, miltefosine, and azithromycin. Treatment of waterborne skin infections includes empiric antibi otic administration ( Table 160-8) and tetanus vaccination if needed. Consensus is that initial empiric antibiotic therapy is broad spectrum, including clindamycin in combination with a fourth-generation cepha losporin, an extended-spectrum fluoroquinolone (i.e., moxifloxacin), or an antipseudomonal penicillin (i.e., piperacillin-tazobactam). 60 If V. v ulnif icus is suspected, treat with doxycycline and a fourth-generation cephalosporin.34 Use clarithromycin or doxycycline for most M. marinum infections, adding rifampin or ethambutol if severe.40 Patients with evidence of necrotizing infections need surgical consultation for opera tive debridement.60 DISPOSITION AND FOLLOW-UP Most episodes of acute gastroenteritis secondary to waterborne pathogens are self-limited. Patients with systemic symptoms, severe dehydration, or comorbid illnesses or patients unable to tolerate oral TABLE 160-8 Treatment of Waterborne Skin Infections Pathogen Clinical Features of Skin Infection Treatment Vibrio vulnificus Cellulitis with hemorrhagic bullae, septicemia Doxycycline 100 milligrams IV twice per day plus fourth-generation cephalosporin; necrotizing infections require emergent surgical debridement Aeromonas species Cellulitis, necrotizing wound infections Mild infections: ciprofloxacin 500 milligrams PO twice per day; severe infections: ciprofloxacin 400 milligrams IV twice per day plus an IV antipseudomonal penicillin or fourth-generation cephalosporin; necrotizing infections require emergent surgical debridement Pseudomonas aeruginosa Hot-tub folliculitis, cellulitis in immunocompromised/ diabetics Hot-tub folliculitis is usually selflimited.

tions: ciprofloxacin 400 milligrams IV twice per day plus an IV antipseudomonal penicillin or fourth-generation cephalosporin; necrotizing infections require emergent surgical debridement Pseudomonas aeruginosa Hot-tub folliculitis, cellulitis in immunocompromised/ diabetics Hot-tub folliculitis is usually selflimited. Severe infection: ciprofloxacin 400 milligrams IV twice per day plus an IV antipseudomonal penicillin or fourthgeneration cephalosporin Mycobacterium marinum Granulomatous skin infections Clarithromycin 500 milligrams PO twice per day or doxycycline 100 milligrams PO twice per day for 3 mo; severe cases: combine with rifampin or ethambutol fluids are bedded (admission or longer observation). Admit those with waterborne skin infections accompanied by systemic illness, suspected necrotizing findings, or comorbid conditions such as immunocom promised states. REFERENCES The complete reference list is available online at www.TintinalliEM.com. CHAPTER Zoonotic Infections Bryan B. Kitch John T. Meredith INTRODUCTION Zoonoses are diseases caused by bacteria, viruses, parasites, or fungi transmitted from vertebrate animals or insects to or from humans. Ticks are one of the most important vectors of human infectious diseases in the world. Exposures or occupations that involve animal contact are risk factors for disease ( Table 161-1). Recent travel, particularly in spring, summer, and early fall, or history of habitation in an underdeveloped country are additional risk factors. Zoonoses can occur at any time of the year, but in temperate climates, most zoonoses happen in the spring and summer. A patient with a zoonotic infection has signs and symp toms similar to many acute infections: fever, headache, myalgias, mal aise, and weakness (Table 161-2). This chapter focuses on the most important tick-borne diseases, upper and lower respiratory zoonoses, and parasitic zoonoses. Many of the parasitic, bacterial, and viral organisms responsible for gastroen teritis share a zoonotic source in addition to a human source. These are discussed in Chapter 73, “Disorders Presenting Primarily With Diar rhea. ” Life-threatening zoonoses such as rabies, malaria, and serious viral infections are discussed in separate chapters.  TICK-BORNE INFECTIONS Ticks parasitize vertebrates in virtually every part of the world. Saliva of some tick species contains anesthetic and inflammatory factors, and some species contain a toxin that paralyzes the host. Ticks feed for several days on the host, and their presence often goes unnoticed for a time; many affected patients do not recall a history of a tick bite. 1 Tick-borne TABLE 161-1 Risk Factors for Zoonotic Infection Risk Category Examples Agricultural workers Farmers, cattle ranchers, sheep ranchers, and migrant workers Animal processing workers Slaughterhouse workers, animal hide processors, and workers in manufacturing who deal with animal products Outdoor enthusiasts Forestry workers, lumbermen, surveyors, park rangers, hunters, spelunkers, and fishermen Pet owners Those living alongside a dog, cat, bird, rodent, rabbit, reptile, or fish Professionals Veterinarians, animal researchers, and animal handlers Immunocompromised patients Those with congenital immunodeficiencies, diabetes mellitus, alcoholism, renal failure, liver failure, cancer, splenectomy, or human immunodeficiency virus Tintinalli_Sec13_p0997-1100.indd 1070 8/2/19 8:12 PM

eptile, or fish Professionals Veterinarians, animal researchers, and animal handlers Immunocompromised patients Those with congenital immunodeficiencies, diabetes mellitus, alcoholism, renal failure, liver failure, cancer, splenectomy, or human immunodeficiency virus Tintinalli_Sec13_p0997-1100.indd 1070 8/2/19 8:12 PM CHAPTER 161: Zoonotic Infections 1071 diseases are often accompanied by a rash. Tick-borne zoonoses have a geographic distribution (Table 161-3) and seasonal variation. TICK REMOVAL, PROPHYLACTIC TREATMENT, AND PREVENTION OF TICK BITES The most effective way to remove an embedded tick is manual extraction with tweezers or blunt angled forceps to grasp the tick as close to the skin surface as possible. Avoid puncturing or grasping the body of the tick because this can lead to rupture of the tick and release of an infectious pathogen. Pull perpendicular to the skin with gentle traction, avoiding twisting or breaking the tick. Remove all residual body parts to limit any granulomatous reaction and infection. After complete removal of the tick, cleanse and disinfect the skin surface. Do not use topical or injected lidocaine or pass sutures through the tick, and avoid the use of gasoline, kerosene, petroleum jelly, or fingernail polish, which all can increase infection or impair complete tick removal. Commercially available tick removal devices exist, although tweezers are effective. 2 Save the removed tick in alcohol to aid in identification, which is helpful if later illness occurs. Use prophylactic treatment of a tick bite in select circumstances. 3 Prophylactic indications include the ability to easily identify the tick as Ixodes scapularis, tick attachment for >36 hours or with obvious tick engorge ment, and a local tick bite in an area with Borrelia burgdorferi carrier rate of >20%.4 In such cases, use a one-time dose of doxycycline 200 milligrams for adults or 4 milligrams/kg in children for Lyme disease prophylaxis. The best method to avoid tick bites is the application of topical DEET (N,N-diethyl-m-toluamide) to exposed skin and treatment of clothing with permethrin. Optimal DEET concentration is 15% to 33%, with less effectiveness if the DEET concentration is >35%. Apply to skin accord ing to label directions. ROCKY MOUNTAIN SPOTTED FEVER The human disease-causing rickettsioses—the spotted fevers—include a number of different species identified in the Americas, Europe, Southwest Asia, Africa, Siberia, western Russia, and Australia. Disease names are based on species and geography: Mediterranean spotted fever, Israel spotted fever, Astrakhan fever, Siberian tick typhus, Queensland tick typhus, African tick bite fever, and so on. Rocky Mountain spotted fever is one of the most severe of the tick-borne illnesses in the United States, with peak occurrence occurring in June and July. The fatality rate for Rocky Mountain spotted fever is <0.5%. More than 60% of reported U.S. cases originate from five states: North Carolina, Tennessee, Oklahoma, Missouri, and Arkansas. 5 The causative organism is Rickettsia rickettsii, a pleomorphic, obligate intracellular organism, and the vectors are the very small Dermacentor (D. variabilis and D. andersoni, the American dog tick) and Rhipicephalus sanguineus ticks (the brown dog tick, found in the American Southwest). Deer, rodents, horses, cattle, cats, and dogs are zoonotic hosts, with higher incidence in communities with free-roaming dog presence. 5 Rickettsia parkeri and other members of the family can possibly cause Rocky Mountain spotted fever and may be responsible for an increase in incidence.

und in the American Southwest). Deer, rodents, horses, cattle, cats, and dogs are zoonotic hosts, with higher incidence in communities with free-roaming dog presence. 5 Rickettsia parkeri and other members of the family can possibly cause Rocky Mountain spotted fever and may be responsible for an increase in incidence. TABLE 161-2 Common Systemic Zoonotic Infections Agent Animal Reservoir Physical Findings Diagnostic Tests Treatment Aeromonas species Fish, reptiles Nonspecific fever, severe crepitant cellulitis with systemic toxicity, gastroenteritis — See Chapter 160, “Food and Waterborne Illnesses” Brucella canis Dogs Nonspecific fever Serologic testing, blood culture Doxycycline plus gentamicin or rifampin. TMP-SMX plus gentamicin in children Capnocytophaga Dogs and cats Fever, septic shock, and meningitis from infected bite Culture of bite wound Amoxicillin-clavulanate or clindamycin. Pip-Tazo or a carbapenem plus clindamycin/vancomycin for shock Chlamydophila psittaci Birds Fever, flulike illness, pneumonia, endocarditis, sepsis Serologic testing and sputum culture Doxycycline. Azithromycin and levofloxacin are alternatives Coxiella burnetii Cattle, sheep, goats, and occasionally cats Fever, pneumonia, hepatitis, meningitis, endocarditis Serologic testing, PCR Doxycycline, with the possible alternative of a fluoroquinolone or macrolide Ehrlichia species Ticks Nonspecific fever, sepsis, meningitis, hepatitis Clinical diagnosis, serologic testing, peripheral blood smear, immunocytologic testing, PCR Doxycycline recommended for all patients (even children and pregnancy). Rifampin is alternative Leptospira species Birds, dogs, rodents Fever, pneumonia, conjunctivitis, lymphadenopathy Darkfield microscopic examination of body fluids, serologic testing Penicillin G IV. Ceftriaxone IV alternative. Mild disease: oral doxycycline or amoxicillin or azithromycin Francisella tularensis Rabbits, cats, wild animals, biting insects Fever, sepsis, meningitis, pneumonia, hepatitis, rash Serologic testing (poses hazards to laboratory staff) IV aminoglycosides. Alternative: Doxycycline or ciprofloxacin Rickettsia rickettsii Ticks Fever, diarrhea, or typical presentation of Rocky Mountain spotted fever Clinical diagnosis, rise in antibody titer between acute and convalescent serum, skin biopsy Doxycycline or chloramphenicol Salmonella enterica Dogs, cats (rarely), reptiles (turtles) Fever, abdominal pain, sepsis, cellulitis, meningitis, endocarditis, septic arthritis Blood or stool culture Fluoroquinolones or third-generation cephalosporins Streptococcus iniae cellulitis Fish, seafood Fever, cellulitis Wound culture, blood culture β-Lactams except aztreonam. Alternatives: azithromycin, clindamycin, fluoroquinolones Yersinia pestis Dogs, cats, rodents Bubonic: fever, headache, buboes; or pneumonic: cough, chills, dyspnea, shock Blood culture, culture of suspected sites Doxycycline, fluoroquinolone, gentamicin, streptomycin, or chloramphenicol Abbreviations: PCR = polymerase chain reaction; Pip-Tazo = piperacillin-tazobactam; TMP-SMX = trimethoprim-sulfamethoxazole. Tintinalli_Sec13_p0997-1100.indd 1071 8/2/19 8:12 PM

h, chills, dyspnea, shock Blood culture, culture of suspected sites Doxycycline, fluoroquinolone, gentamicin, streptomycin, or chloramphenicol Abbreviations: PCR = polymerase chain reaction; Pip-Tazo = piperacillin-tazobactam; TMP-SMX = trimethoprim-sulfamethoxazole. Tintinalli_Sec13_p0997-1100.indd 1071 8/2/19 8:12 PM 1072 SECTION 13: Infectious Diseases TABLE 161-3 Tick-borne Infections Disease Primary Vector Animal Reservoir Clinical Features Geographic Distribution Babesiosis Ixodes dammini, I. scapularis, and I. pacificus Cattle, horses, dogs, cats, rodents, deer Fatigue, malaise, anorexia, nausea, headache, sweats, rigors, abdominal pain, emotional lability, depression, dark urine, hepatomegaly, fever, petechiae, ecchymosis, occasional rash, and occasionally, pulmonary edema Northeast and north-central United States Colorado tick fever Dermacentor andersoni (wood tick) Deer, marmots, porcupines Fever, chills, headache, myalgias, nausea, vomiting, photophobia, abdominal pain, and occasional sore throat; also may have conjunctivitis, lymphadenopathy, hepatosplenomegaly, stiff neck, retro-orbital pain, weakness, and lethargy Western and northwestern United States and southwestern Canada Anaplasmosis I. scapularis, I. pacificus Dogs, deer, other mammals Fevers, chills, malaise, headache, nausea, muscle aches, cough, sore throat, and pulmonary infiltrates (especially in children) Japan, Malaysia, and the eastern, northeastern, and north-central United States Ehrlichiosis Amblyomma americanum (lone star tick) Dogs, deer, other mammals Fevers, chills, malaise, headache, nausea, muscle aches, cough, sore throat, and pulmonary infiltrates (especially in children) Japan, Malaysia, Europe, and southeastern and south-central United States Lyme disease (Borrelia burgdorferi) I. dammini Deer, sheep, deer mice Erythema migrans, meningitis, encephalitis, neuropathy, and joint and heart symptoms Atlantic central and north-central United States, Europe Rocky Mountain spotted fever (Rickettsia rickettsii) D. andersoni and Dermacentor variabilis (dog tick) North American mammals Petechiae, purpura, pulmonary infiltrates, jaundice, myocarditis, hepatosplenomegaly, meningitis, encephalitis, and lymphadenopathy Most of the continental United States, although more prevalent in the southeast and south-central United States Relapsing fever (Borrelia species) Ornithodoros species Human body lice, wild rodents, humans Fever, chills, headache, myalgias, and arthralgias; pain, nausea, vomiting, and hypotension Worldwide Southern tick-associated rash illness A. americanum Ticks; unclear if other reservoir exists Erythema migrans, fever, headache, myalgias Eastern, southeastern, and south-central United States Tularemia (Francisella tularensis) Dermacentor spp. and Amblyomma spp. Rabbits, deer, dogs Pneumonia, regional lymphadenopathy and headache, cough, myalgias, arthralgias, nausea, vomiting, ulceration at inoculation site, and ocular findings Northern hemisphere, North America, northern Asia, Europe  CLINICAL FEATURES The diagnosis relies on epidemiologic features and the clinical exclusion of other diseases. Early signs and symptoms of Rocky Mountain spot ted fever are fever, headache, myalgia, and malaise. Additionally, other nonspecific findings include lymphadenopathy, abdominal pain, nausea, vomiting, diarrhea, and headache. Late in the disease course, confusion, meningismus, renal failure, respiratory failure, and myocarditis may occur. The classic clinical picture is the triad of fever, rash, and tick bite, but only about half of patients can recall a tick bite. The rash occurs on days 2 to 4 after the onset of fever but is absent in approximately 20% of patients. Most patients do not have a petechial rash when they seek initial medical care.

occur. The classic clinical picture is the triad of fever, rash, and tick bite, but only about half of patients can recall a tick bite. The rash occurs on days 2 to 4 after the onset of fever but is absent in approximately 20% of patients. Most patients do not have a petechial rash when they seek initial medical care. 1 The rash occurs earlier in children than in adults and begins as small blanching erythematous to pink macules and becomes petechial later. This characteristic macu lopapular rash begins on the hands, feet, wrists, and ankles, and then spreads centripetally up the trunk. The rash is not pathognomonic and may occur in other illnesses. Additionally, the rash is easily overlooked early in infection and in those with dark skin. Another feature to rec ognize is the possibility of a nonexudative conjunctival injection with bilateral periorbital edema, resembling that found in toxic shock syndrome or Kawasaki’s disease. Abdominal distention and organomegaly may exist on physical exam.  DIAGNOSIS AND TREATMENT Immunoglobulin G– or immunoglobulin M–specific antibodies are not detectable in acute-phase serum. Laboratory abnormalities are usually nonspecific, but the combination of normal white and red cell counts, thrombocytopenia, mild elevation of liver enzymes (aspartate ami notransferase and alanine aminotransferase), and hyponatremia suggests Rocky Mountain spotted fever , especially if the disease is advanced. Hypoalbuminemia may be present and is the cause of edema. In addition to clinical patterns, diagnosis confirmation with a rise in antibody titer between acute and convalescent serum, skin biopsy with immunofluorescent testing, or culture is possible, although none of these are useful for ED diagnosis. Preferred treatment is doxycycline (Table 161-4). Given the long half-life of doxycycline (18 to 21 hours), several days of a higher dose regimen may be required to achieve rapid therapeutic response in the critically ill patient. The risk of cosmetically perceptible tooth staining is small for a single course of treatment. Use doxycycline therapy as the treatment of choice for all rickettsial diseases, including Rocky Mountain spotted fever, in children of all ages. TICK PARALYSIS Many tick species secrete neurotoxic substances from salivary glands of attached ticks. Tick paralysis occurs worldwide, in Australia, Africa, Europe, and North America, and is more common in children than adults. Prolonged tick attachment (5 to 7 days) can result in host paralysis. Symptoms are ascending weakness, beginning in the lower extremities, and moving upward to the trunk, upper extremities, and head over hours to days. Cerebrospinal fluid analysis is normal. Diag nosis is made upon finding a tick on the body. Tick removal leads to recovery in 24 hours. LYME DISEASE The first reports of Lyme disease were in Europe about 100 years ago based on descriptions of the rash, erythema chronicum migrans. Lyme disease is the most common vector-borne zoonotic infection in the United States, with approximately 30,000 annual cases reported. Based on public health data and insurance information, the actual number of patients diagnosed with Lyme disease may be closer to 300,000 per year. Lyme disease is reported in Europe, China, Japan, Australia, parts of Russia, and in all U.S. continental states, with 96% of the reported cases Tintinalli_Sec13_p0997-1100.indd 1072 8/2/19 8:12 PM

ta and insurance information, the actual number of patients diagnosed with Lyme disease may be closer to 300,000 per year. Lyme disease is reported in Europe, China, Japan, Australia, parts of Russia, and in all U.S. continental states, with 96% of the reported cases Tintinalli_Sec13_p0997-1100.indd 1072 8/2/19 8:12 PM CHAPTER 161: Zoonotic Infections 1073 originating from 14 states clustered in the northeast and upper midwest. Peak transmission occurs in May through August. The responsible organism is B. burgdorferi , a spirochete, and the vector is the Ixodes deer tick, also known as the black-legged tick. The overall risk of Lyme disease after a deer tick bite is low, about 3% in endemic areas. However, the risk of infection is proportional to the length of time the tick feeds on the host, with minimal to no risk associated with tick attachment duration of <36 hours. 4,8  CLINICAL FEATURES Lyme disease has three stages. The first stage is local and often with erythema migrans: an erythematous plaque with central clearing, seen in approximately 60% to 80% of cases. 1 It develops within 2 to 30 days at the site of the tick bite and is a result of a vasculitis. There may be accompanying fever, chills, fatigue, myalgias, arthralgias, and lymph adenopathy. The rash may persist for up to 1 month and recur in the secondary stage of Lyme disease. Untreated erythema migrans resolves spontaneously in 3 to 4 weeks. This rash causes few symptoms and may go unnoticed by the patient. The second stage, early disseminated disease, develops with the reproduction and spread of the Borrelia spirochete, occurring within a few days to months of the initial infection. This stage has fever, adenopathy, neuropathies, cardiac abnormalities, arthritic complaints, and skin lesions. Multiple annular/target-shaped skin findings occur in up to 50% of the patients infected and are the most characteristic component of the secondary stage of illness. The most common neurologic symptom in the secondary stage of illness is the development of cranial neuritis, most often unilateral or bilateral facial nerve palsy . Facial palsy can also occur along with the initial rash of erythema migrans. Neuroborreliosis occurs in 15% of the untreated cases and can consist of periodic headache, neck stiffness, difficulty in mentation, cerebellar ataxia, myelitis, encephalitis, motor or sensory radiculoneuritis, mononeuritis multiplex, and facial palsy. 9 Asymmetric oligoarticular arthritis of the large joints, with a particular predilection for the knees, is another complication. Brief attacks of asymmetric oligoarticular arthritis are common in the untreated patient in the sec ondary stage of illness. Attacks are characteristically separated by months of remission. Cardiac abnormalities occur in up to 8% of patients and present as varying degrees of atrioventricular block, sometimes requiring the insertion of a temporary pacemaker for stabilization. Additionally, myopericarditis may also be a manifestation on initial presentation. The late disseminated stage of illness occurs months to years after the initial infection and is characterized by chronic arthritis, myocardi tis, subacute encephalopathy, axonal polyneuropathy, and leukoencephalopathy. 9 The advanced, chronic neurologic forms of Lyme disease can persist for over 10 years. Additionally, between 10% and 20% of patients treated with antibiotics have persistent symptoms, usually muscle and joint aches with fatigue and perhaps an autoimmune response persistent after the initial infection.  DIAGNOSIS AND TREATMENT Diagnosis is clinical early in disease when erythema migrans is present; testing diagnoses later stages of Lyme disease.

nts treated with antibiotics have persistent symptoms, usually muscle and joint aches with fatigue and perhaps an autoimmune response persistent after the initial infection.  DIAGNOSIS AND TREATMENT Diagnosis is clinical early in disease when erythema migrans is present; testing diagnoses later stages of Lyme disease. 8 For the latter, use polymerase chain reaction testing, polyvalent fluorescence immunoassay, or Western immunoblot testing, 9 because B. burgdorferi is difficult to culture. Treatment of Lyme disease is with doxycycline (preferred agent) or amoxicillin. Neurologic symptoms or other persistent manifestations require ceftriaxone therapy (Table 161-4). A previously marketed vac cine no longer exists, because it conferred no ongoing immunity. EHRLICHIOSIS AND ANAPLASMOSIS Ehrlichiosis is a group of zoonotic diseases caused by the Ehrlichia genus, gram-negative pleomorphic coccobacilli that will infect circulating leukocytes. 1 Infection due to Ehrlichia chaffeensis is also called human monocytic ehrlichiosis. The disease vector is the lone star tick, Amblyomma americanum. The major animal reservoir in North America is the white-tailed deer in the southeastern United States, with dogs and mice carrying several less common species of the pathogen. 10 Disease incidence rose from 0.8 to 3 cases per million in the United States in 2000 to 2007, partly attributed to increased recognition. It also exists in Europe. The mortality rate in confirmed cases varies between 1% and 3% depending on causative agent. Symptoms usually develop within 1 to 2 weeks of a tick bite. 11 Clinical signs and symptoms are fever, headache, malaise, nausea, vomiting, diarrhea, abdominal pain, and arthralgias. Fever is present in the vast TABLE 161-4 Tick-borne Zoonotic Infections and Specific Treatment Tick-borne Zoonotic Infection Specific Treatment Rocky Mountain spotted fever Doxycycline 100 milligrams PO or IV twice a day for 7 d, or for 2 d after temperature normalizes. Some recommendations exist for an initial loading dose of 200 milligrams. For children weighing <45 kg, the dose is 2.2 milligrams/kg twice daily. Although doxycycline is contraindicated for use in pregnancy, it may be warranted in life-threatening situations. Chloramphenicol is an alternative; however, it has multiple toxic effects and contraindications and may be difficult to obtain. Dosing is 50 milligrams/kg/d divided into 4 doses for 7 d. Lyme disease Primary stage or mild secondary: 14–21 d of doxycycline (100 milligrams PO twice a day), amoxicillin (500 milligrams PO 3 times a day in adults, 50 milligrams/kg/d divided 3 times a day in children), or cefuroxime (500 milligrams PO twice a day in adults, 30 milligrams/kg/d divided 3 times a day in children). Macrolides possible but less effective. Severe illness, CNS positive, or high-degree heart block: ceftriaxone 2 grams IV for 14–30 d. A single 200-milligram oral dose of doxycycline given within 72 h of a high-risk deer tick bite is effective in preventing Lyme disease. Tick-borne relapsing fever Doxycycline (100 milligrams PO/IV twice a day for 7–10 d). Alternative: erythromycin (500 milligrams PO/IV 4 times a day for 7–10 d). Chloramphenicol is an alternative. Colorado tick fever Treatment is supportive. Southern tick-associated rash illness Treatment is supportive, often treated cautiously as Lyme with doxycycline as above. Tularemia Adults: streptomycin, 1 gram IM/IV twice a day, or gentamicin/tobramycin, 5 milligrams/kg IV divided every 8 h. Treat for 10 d. Children: streptomycin, 15 milligrams/kg IM twice daily (should not exceed 2 grams/d). Mild disease: ciprofloxacin, 750 milligrams PO twice a day, or doxycycline, 100 milligrams PO twice a day. Treat for 21 d.

cin, 1 gram IM/IV twice a day, or gentamicin/tobramycin, 5 milligrams/kg IV divided every 8 h. Treat for 10 d. Children: streptomycin, 15 milligrams/kg IM twice daily (should not exceed 2 grams/d). Mild disease: ciprofloxacin, 750 milligrams PO twice a day, or doxycycline, 100 milligrams PO twice a day. Treat for 21 d. Prophylaxis for lab exposures: doxycycline, 100 milligrams PO twice a day, or ciprofloxacin, 500 milligrams PO twice a day. Treat for 14 d. Babesiosis Atovaquone (750 milligrams PO every 12 h) plus azithromycin (500 milligrams PO on day 1, then 250 milligrams daily). Treat for 10 d. If relapse occurs, treat for the longer duration: 6 weeks or 2 weeks after negative blood smear. Severe disease in adults: clindamycin (1200 milligrams IV twice a day or 600 milligrams PO 3 times a day) + quinine (650 milligrams PO 3 times a day). Treat for 7–10 d. Ehrlichiosis and anaplasmosis Doxycycline, 100 milligrams PO twice a day for 7–14 d. For children weighing <45 kg, the dose is 2.2 milligrams/kg twice a day. Tintinalli_Sec13_p0997-1100.indd 1073 8/2/19 8:12 PM

wice a day or 600 milligrams PO 3 times a day) + quinine (650 milligrams PO 3 times a day). Treat for 7–10 d. Ehrlichiosis and anaplasmosis Doxycycline, 100 milligrams PO twice a day for 7–14 d. For children weighing <45 kg, the dose is 2.2 milligrams/kg twice a day. Tintinalli_Sec13_p0997-1100.indd 1073 8/2/19 8:12 PM 1074 SECTION 13: Infectious Diseases majority of cases (97%). Rash is present in 30% of adults and has no pathognomonic features. 12 With disease progression, a minority of patients develop renal failure, respiratory failure, and encephalitis. The acute phase of illness lasts <4 weeks, with the majority of patients recovering and proceeding on to a convalescent phase. Laboratory studies can demonstrate leukocytopenia, thrombocytopenia, and elevation of hepatic enzymes.  DIAGNOSIS AND TREATMENT Diagnosis is made clinically but can be confirmed by laboratory testing once treatment has begun. Peripheral blood smear may show colonies of ehrlichiae in the WBCs in 20% of infected patients. Polymerase chain reaction is specific but not sensitive and is best done in the first week of illness. Antibody tests are negative in 85% of patients during initial infection. The reference criterion test is immunofluorescence assay. Treatment is with doxycycline until 3 to 5 days after fever resolution or 10 to 14 days after resolution of CNS symptoms in severe disease. Rifampin is an alternative in those with contraindications to doxycycline. Anaplasmosis is a tick-borne disease caused by the bacteria Anaplasma phagocytophilum.13 Older terms for the disease are human granulocytic ehrlichiosis and human granulocytic anaplasmosis. The vector is the blacklegged tick, I. scapularis, as well as the western black-legged tick, Ixodes pacificus. The clinical presentation of this disease is similar to ehrlichiosis, with geography of tick prevalence as the key difference between the two. Testing is similar, and treatment is also with doxycycline. TICK-BORNE RELAPSING FEVER Relapsing fever is caused by several varieties of gram-negative Borrelia spirochetes. It was first described in West Africa and is now worldwide. Within the United States, it is rarely found east of Texas. 14 Ornithodoros ticks (soft ticks that can survive for years between meals) are the vectors, and the principal zoonotic reservoirs are wild rodents, specifically tree squirrels and chipmunks. 15 The classic risk factor is sleeping in rustic mice-infested structures in the wilderness of the western United States. The initial presentation may be that of a rash or a 2- to 3-mm pruritic eschar at the site of a tick bite. An average incubation period of 7 days precedes the onset of fever, chills, cephalgia, myalgia, arthralgia, abdominal pain, and general malaise. Headache and myalgia occur in >90% of cases. 15 Characteristically, the 3-day-long febrile episodes are inter spersed with 7-day-long afebrile periods, which may cycle one to four times before resolution. 15 Untreated, the disease is usually self-limited, with deaths occurring mostly at the extremes of age. Leukocytosis and thrombocytopenia are the typical laboratory findings.  DIAGNOSIS AND TREATMENT Diagnosis confirmation is with the appearance of spirochetes on dark field microscopy or Wright-Giemsa–stained peripheral blood smears, with a 70% sensitivity if obtained during a febrile period. Patients with relapsing fever may test false positive on Lyme disease assays due to protein cross-reactivity. 15 Treatment is with tetracycline or erythromycin. Use IV ceftriaxone for 10 to 14 days if any CNS involvement exists.

tained peripheral blood smears, with a 70% sensitivity if obtained during a febrile period. Patients with relapsing fever may test false positive on Lyme disease assays due to protein cross-reactivity. 15 Treatment is with tetracycline or erythromycin. Use IV ceftriaxone for 10 to 14 days if any CNS involvement exists. 15 Patients in an endemic area with a confirmed tick bite can receive post exposure doxycycline for prophylaxis.16 COLORADO TICK FEVER Colorado tick fever is caused by an RNA virus of the genus Coltivirus in the family Reoviridae.17 The principal vector is the wood tick, D. andersoni, and the zoonotic reservoirs are deer, marmots, and porcupines. The disease is endemic to the western mountainous regions of the United States with elevations between 4000 and 10,000 ft. Transmission to humans can occur with short periods of tick attachment. The incubation period is 3 to 5 days, and the onset of illness has fever, chills, headache, myal gias, and photophobia. There may be a macular or petechial rash in a minority of patients. The disease is self-limited, and complications are rare, although some patients may experience recurrent fever after 1 to 2 days of improvement.  DIAGNOSIS AND TREATMENT Diagnosis is most often based on history, clinical findings, and geogra phy. Treatment is supportive.17 SOUTHERN TICK-ASSOCIATED RASH ILLNESS (STAR) Southern tick-associated rash illness (STAR) is an illness that clinically presents in a manner nearly identical to Lyme disease. 18 This disease has the typical target-shaped rash of primary Lyme and may be accompanied by nonspecific symptoms such as fever, myalgias, headache, and fatigue. This illness is transmitted by the lone star tick, A. americanum, which is endemic to the eastern, southeastern, and south-central United States. Unlike Lyme disease, southern tick-associated rash illness is not known to cause delayed presentations of illness, nor does it cause cardiac or CNS involvement. The disease is thought to be transmitted directly by the tick, but no animal reservoirs or causative bacteria have been discovered. Although it is thought to be a benign and self-limited disease requiring only supportive care, southern tick-associated rash illness’s clinical mimicry of Lyme disease leads many providers to empirically treat for the latter. TULAREMIA Tularemia is caused by a small, gram-negative, nonmotile intracellular coccobacillus, Francisella tularensis. The disease is found in North America, northern Asia, and Europe. The zoonotic vectors are ticks of the Dermacentor species (wood tick, dog tick) and the Amblyomma species (lone star tick), as well as various flies. The principal zoonotic reservoirs are rabbits, hares, and deer. 17 Tularemia is contracted through tick/fly bites, by inhalation, or through open wounds while in contact with an infected zoonotic host. Incubation is often between 3 and 6 days but may range from 2 hours to 3 weeks. The clinical presentation depends on the method of inoculation, and the clinical forms are called ulceroglandular, glandular, typhoidal, pneumonic, oculoglandular, and oropharyngeal. The ulceroglandular form is the most common, occurring in 80% of cases, 17 with a maculopapular skin lesion that ulcerates, followed by painful regional adenopathy and systemic symptoms. The glandular form consists of painful adenopathy without ulcerations. The typhoidal form, occurring in 20% to 30% of cases, consists of high fever, chills, cephalgia, and abdominal pain with an absence of skin and lymph involvement. Typhoidal tularemia has a slower tachycardia than would be expected given the fever magnitude. It is the form of the disease with highest morbidity, complications, and organ failure.

ring in 20% to 30% of cases, consists of high fever, chills, cephalgia, and abdominal pain with an absence of skin and lymph involvement. Typhoidal tularemia has a slower tachycardia than would be expected given the fever magnitude. It is the form of the disease with highest morbidity, complications, and organ failure. The oculoglandular form and pneumonic form are the result of deposition into the eyes or inhalation of the F. tularensis bacterium. Pneumonic tularemia has up to a 50% mortality rate and is the most lethal form of the disease. Laboratory findings are nonspecific.  DIAGNOSIS AND TREATMENT Confirmatory testing is difficult and poses health risks to laboratory staff. First-line treatment is with streptomycin; gentamicin, ciprofloxacin, imipenem, doxycycline, and chloramphenicol are alternative therapies. Prevention of exposure and early treatment are key measures to prevent adverse outcomes. Think of this infection in endemic areas. Due to the ease of transmission and lethality, F. tularensis is a possible agent of biologic warfare/terrorism (Table 9-1). BABESIOSIS Babesiosis is a malaria-like disease transmitted by ticks, with the etiologic agents being protozoan parasites. Babesia microti is the most common causative organism in the United States, with sporadic cases caused by Babesia duncani on the Pacific coast. 20 The major zoonotic reservoirs are domesticated mammals, rodents, and deer. Ixodes ticks function as the principal vector globally. Babesiosis is also transmitted through blood transfusions, with about 160 cases reported since 1979. Clinically, the presentation occurs 1 to 4 weeks after exposure with Tintinalli_Sec13_p0997-1100.indd 1074 8/2/19 8:12 PM

domesticated mammals, rodents, and deer. Ixodes ticks function as the principal vector globally. Babesiosis is also transmitted through blood transfusions, with about 160 cases reported since 1979. Clinically, the presentation occurs 1 to 4 weeks after exposure with Tintinalli_Sec13_p0997-1100.indd 1074 8/2/19 8:12 PM CHAPTER 161: Zoonotic Infections 1075 TABLE 161-5 Selected Zoonotic Infections and Specific Treatment Selective Zoonotic Infections Specific Treatment West Nile/Powassan encephalitis Supportive care. Brucellosis (Brucella species) Mild disease: doxycycline, 100 milligrams PO twice a day for 6 weeks, + gentamicin, 5 milligrams/kg IV daily for 7 d. Alternative: doxycycline, 100 milligrams PO twice a day, + rifampin, 600–900 milligrams PO daily for 6 weeks. Joint involvement: doxycycline, 100 milligrams PO twice a day, + rifampin, 600–900 milligrams PO daily for 3 months, + gentamicin, 5 milligrams/kg IV once daily for first 7 d. Neurologic involvement: doxycycline, 100 milligrams IV/PO twice a day, + rifampin, 600–900 milligrams PO daily, + ceftriaxone, 2 grams IV twice a day. Treat until cerebrospinal fluid normalizes. Psittacosis (Chlamydophila psittaci) Doxycycline, 100 milligrams PO for 5–7 d. Alternative: azithromycin dose pack or levofloxacin, 750 milligrams PO for 5–7 d. Q fever (Coxiella burnetii) Doxycycline, 100 milligrams PO twice a day for 2–3 weeks. Alternative: consider 2–3 weeks of a fluoroquinolone or a macrolide. Pasteurellosis (Pasteurella multocida) Amoxicillin-clavulanate, 875/125 milligrams PO twice a day for 7–10 d. Alternative therapies based on culture data and presence of Staphylococcus coinfection. Often resistant to cephalexin, clindamycin, and macrolides. Plague (Yersinia pestis) Gentamicin, 5 milligrams/kg IV daily for 10 d. Alternative: streptomycin, 15 milligrams/kg IV/IM twice a day for 10 d. Postexposure prophylaxis: doxycycline, 100 milligrams PO twice a day, or ciprofloxacin, 500 milligrams PO twice a day. Treat for 7 d. Hantavirus Treatment consists of supportive care with attention to adequate oxygenation. Toxocariasis (Toxocara canis) Moderate to severe disease: albendazole, 400 milligrams PO twice a day, with/without prednisone, 60 milligrams/d for allergic response. Treat for 5 d. Alternative: mebendazole, 100–200 milligrams PO twice a day for 21 d. Dipylidiasis (dog tapeworm) Praziquantel, 5–10 milligrams/kg PO, one-time dose. Alternative: niclosamide, 2 grams PO, one-time dose Leptospirosis Mild disease: doxycycline, 100 milligrams PO twice a day for 5–7 d. Alternative: azithromycin, 500 milligrams PO daily for 3 d. Severe disease: penicillin G, 1.5 million units IV every 6 h for 7 d, or ceftriaxone, 2 grams IV daily for 7 d. Alternative: doxycycline, 100 milligrams IV for 7 d. generalized malaise, anorexia, fever, and chills that can progress to intermittent sweats, myalgia, headache, and hemolytic anemia. Splenectomy and immunosuppression are risk factors. Laboratory tests demonstrate hemolysis, liver dysfunction, anemia, thrombocytopenia, and renal failure. Coinfection with Lyme disease or anaplasmosis/ehrlichiosis is common; patients with severe disease or disease refractory to treatment should be considered for alternative etiologies of illness.  DIAGNOSIS AND TREATMENT Diagnose this infection by finding intraerythrocytic ring forms resem bling malaria on a Giemsa- or Wright-stained peripheral blood smear, although false-negative results can occur when the level of parasitism is low. Treatment duration is typically for 7 to 10 days with atovaquone plus azithromycin or clindamycin, with quinine added for severely ill patients (Table 161-4).

g forms resem bling malaria on a Giemsa- or Wright-stained peripheral blood smear, although false-negative results can occur when the level of parasitism is low. Treatment duration is typically for 7 to 10 days with atovaquone plus azithromycin or clindamycin, with quinine added for severely ill patients (Table 161-4).  ZOONOTIC ENCEPHALITIS AND MENINGITIS Zoonotic encephalitis is most often an arboviral infection transmitted hematologically by an arthropod or insect vector from an animal host. There are multiple distinct arboviruses that cause zoonotic encephalitis in the United States and Canada. Furthermore, encephalitis may be seen in the nonviral zoonotic infections of Bartonella henselae, Brucella canis, borreliosis, Coxiella burnetii, Ehrlichia species, listeriosis, leptospirosis, Lyme disease, Rocky Mountain spotted fever, psittacosis, and toxoplas mosis. 21 See Chapter 174, “Central Nervous System and Spinal Infec tions, ” for additional discussion. The first clinical signs and symptoms are nonspecific: malaise, myalgia, and fever. Next often comes headache and a sudden decline in mental status. Head CT scan is usually normal. The cerebrospinal fluid is often abnormal, showing a slightly elevated opening pressure, normal to slightly elevated protein concentration, normal glucose levels, and predominance of lymphocytes. The infectious agent is rarely isolated from the cerebrospinal fluid. Enzyme-linked immunosorbent assay of serum can detect most arboviral infections causing encephalitis. Treatment is supportive. Consider treatable causes of encephalitis, such as herpes simplex or varicella, in the differential diagnosis. The West Nile virus is an arbovirus that can cause a flulike illness, West Nile fever or West Nile virus encephalitis . Infected mosquitoes transmit the virus to humans and other animals through bites. Approximately 20% of patients infected develop symptomatic illness, with <1% having severe or potentially fatal infection. 22 Although antibody responses can confirm disease, lab testing is usually not specific. Treat ment for West Nile virus encephalitis is supportive (Table 161-5). Powassan disease is an arbovirus similar to West Nile but is trans mitted by the deer tick rather than mosquitos. The infection begins with a nonspecific prodrome of fever and chills, but often progresses to a viral encephalitis. 23 Diagnosis is by specialty tests at national laboratories, but the disease should be suspected in areas prone to Lyme disease. Zoonotic meningitis can be caused by brucellosis, listeriosis, plague, salmonellosis, tularemia, leptospirosis, Lyme disease, ehrlichiosis, Q fever, Rocky Mountain spotted fever, or psittacosis. Cerebrospinal fluid is almost always abnormal, showing a slightly elevated opening pres sure, normal to slightly elevated protein concentration, normal glucose levels, and predominance of lymphocytes. Treatment is directed toward the specific organism cultured from the cerebrospinal fluid. However, empiric antibiotic coverage should be administered immediately in any presumptive case of meningitis in an effort to reduce mortality and morbidity (see Chapter 174, “Central Nervous System and Spinal Infections”). Tintinalli_Sec13_p0997-1100.indd 1075 8/2/19 8:12 PM

nism cultured from the cerebrospinal fluid. However, empiric antibiotic coverage should be administered immediately in any presumptive case of meningitis in an effort to reduce mortality and morbidity (see Chapter 174, “Central Nervous System and Spinal Infections”). Tintinalli_Sec13_p0997-1100.indd 1075 8/2/19 8:12 PM 1076 SECTION 13: Infectious Diseases  UPPER RESPIRATORY ZOONOTIC INFECTIONS Recurrent pharyngitis in a household member can have a zoonotic source, sometimes the household pet. Case reports exist where domestic animals in cohabitation with humans were associated with group A streptococcal pharyngitis recurrence; however, current practice guidelines on infection can find no causal link. 24 Prolonged exudative pharyngitis raises the suspicion of a zoonotic origin or atypi cal pharyngitis, particularly if the exudative pharyngitis includes systemic symptoms and leukocytosis, and is refractory to standard antistreptococcal therapy. Dogs and domesticated farm animals can be the source of Streptococcus species, Corynebacterium ulcerans, Yer sinia species, and viral vesicular stomatitis. All of these zoonoses can present as an exudative pharyngitis. Nondomesticated animals can be a source of exudative pharyngitis as a result of Bordetella species, F. tularensis, Streptobacillus moniliformis, and Yersinia pestis. Birds carry Chlamydophila psittaci, which can cause an atypical exudative pharyn gitis in humans.  LOWER RESPIRATORY ZOONOTIC INFECTIONS Zoonotic pneumonia presents as an atypical, community-acquired pneumonia with systemic symptoms. Most often, the presentation is productive or nonproductive cough, fever, chills, headache, myalgias, and a nonspecific rash. Symptoms can progress very rapidly. Ask about animal exposure, occupation, and recent travel. Consider zoonotic pneumonia as a source of gram-negative community-acquired pneu monia and in any case of atypical pneumonia with systemic symptoms (Table 161-6). ANTHRAX Inhalation anthrax (Bacillus anthracis) is acquired most often from handling unsterilized, imported animal hides or imported raw wool; anthrax is generally fatal. Inhalation anthrax is a mediastinitis without alveolar involvement rather than pneumonia. Initial symptoms are similar to influenza with a slightly higher propensity for dyspnea. Illness can progress to respiratory failure in 2 to 3 days, with marked mediastinal and hilar edema. Anthrax vaccination is available primarily for populations at high risk of exposure to aerosolized B. anthracis spores such as military personnel and laboratory workers. A 60-day antibiotic course combined with a three-dose vaccination course used in postexposure prophylaxis may aid in preventing anthrax postexposure, although this regimen is not presently approved by the U.S. Food and Drug Administration. 26 Antibiotics typically used in inhalation anthrax are doxycycline or ciprofloxacin, plus an additional one or two agents for synergy, including penicillin G, vancomycin, rifampin, or other agents for which the strain is suspected to be sensitive. Cephalosporins are contraindicated due to resistance. BRUCELLOSIS Brucellosis ( Brucella species) occurs most often from the consump tion of unpasteurized dairy products. Reports of slaughterhouse workers exposed to aerosols containing Brucella bacteria becoming ill exist. 27 In the rare inhalation form of Brucellosis , patients have the appearance of an upper respiratory infection with a cough, productive sputum, hoarseness of voice, dyspnea, and wheezing. There are no pathognomonic signs on chest radiograph, and a variety of findings may be present including pneumonia, adenopathy, effusion, granulo mas, and effusion. With long-standing resolution, calcified granulo mas may remain.

ory infection with a cough, productive sputum, hoarseness of voice, dyspnea, and wheezing. There are no pathognomonic signs on chest radiograph, and a variety of findings may be present including pneumonia, adenopathy, effusion, granulo mas, and effusion. With long-standing resolution, calcified granulo mas may remain. 28 Doxycycline combined with rifampin is effective therapy; the recommended duration is 6 weeks to prevent recurrence 27 (Table 161-6). PSITTACOSIS Psittacosis (parrot fever, parrot disease) is caused by Chlamydophila psittaci, an organism common to most birds and domesticated fowl. Psittacosis is the term for disease contracted from parrots, and ornithosis is the term for disease contracted from pigeons, sparrows, ducks, hens, and many other birds. This disease is rare, with few cases reported annually in the United States, although underreporting is likely due to the often mild unrecognized form of disease. 29 Human acquisition is from the inhalation of dust from dried bird feces, feather dust, aerosolized avian respiratory secretions, or direct bird contact. 29 Psittacosis is character ized by an incubation period of 5 to 14 days followed by abrupt onset of fever, chills, cephalgia, myalgia, and generalized malaise. Pneumonia is atypical, with a nonproductive cough and lobar or interstitial infiltrates on chest radiograph. Extrapulmonary manifestations including endo carditis, hepatitis, cranial nerve palsies, and acute interstitial nephritis are possible. Diagnosis is based on clinical suspicion for the disease and confirmation of isolation of C. psittaci from respiratory secretions or by immunoglobulin M immunoassay. Doxycycline is the mainstay of treatment, with most patients responding rapidly to therapy. Tetracycline is also an option along with macrolides 29 (Table 161-6). Q FEVER Q fever (Coxiella burnetii) is a rickettsial infection acquired by aerosol inhalation primarily; however, arthropod vector transmission is possible. 30 The primary reservoirs are cattle, sheep, and goats, with bacterial shedding in urine, afterbirth products, and feces. The organism is highly resistant to environmental degradation. The disease is often self-limited, with variable pulmonary manifestations and extrapulmo nary findings. In addition to pulmonary infiltrates, severe headache, pericarditis, myocarditis, endocarditis, and a nonjaundiced hepatitis can occur. The majority of patients have nonspecific infiltrates on chest radiograph. 30 Doxycycline is the treatment of choice for acute Q fever and is most effective in reducing duration of symptoms and risk of complications when initiated within the first 3 days of illness. Q fever may rarely progress to a chronic infective state with fatigue and extrapulmonary manifestations being predominant findings (Table 161-6). PASTEURELLOSIS Pasteurellosis (Pasteurella multocida ) is endemic to the normal oral flora of cats and most dogs. Classically, infection is associated with necrotizing cellulitis from bite wounds. Rarely bronchitis, bronchopneumonia, and suppurative pleural effusion occur as a result of pulmonary infection. Treatment is with amoxicillin-clavulanate, doxycycline, penicillin, or a third-generation cephalosporin (Table 161-6). PULMONIC PLAGUE Between 1000 and 2000 cases of plague are reported each year to the World Health Organization, with mortality rates of approximately 10%. Most human cases today are in sub-Saharan Africa. In the United States, pulmonary plague (Yersinia pestis) is most often found in rock squirrels and ground rodents of the Southwest. Cats can be carriers of plague, whereas dogs are resistant to the disease. The principal vector is the rodent flea, with the majority of infected fleas globally found on black rats or brown sewer rats.

States, pulmonary plague (Yersinia pestis) is most often found in rock squirrels and ground rodents of the Southwest. Cats can be carriers of plague, whereas dogs are resistant to the disease. The principal vector is the rodent flea, with the majority of infected fleas globally found on black rats or brown sewer rats. 31 Humans and household pets become infected when bitten by a harboring flea or by consuming other infected animals. Humans may also be infected by inhalation of animal secretions. Incubation period from a flea bite to disease ranges from 2 to 10 days. Often an eschar develops at the site of the flea bite, followed by the development of a bubo, an enlarged, suppurative, proximal lymph node. Sepsis and pneumonia from hematologic spread occur following the bubo appearance. The disease is rapidly fatal if not aggressively treated. Start treatment when plague is suspected, using parenteral strep tomycin or gentamicin. Transition to oral therapy with doxycycline, Tintinalli_Sec13_p0997-1100.indd 1076 8/2/19 8:12 PM

s and pneumonia from hematologic spread occur following the bubo appearance. The disease is rapidly fatal if not aggressively treated. Start treatment when plague is suspected, using parenteral strep tomycin or gentamicin. Transition to oral therapy with doxycycline, Tintinalli_Sec13_p0997-1100.indd 1076 8/2/19 8:12 PM CHAPTER 161: Zoonotic Infections 1077 TABLE 161-6 Zoonotic Pneumonias Disease Organism Reservoirs Treatment Inhalation anthrax Bacillus anthracis Imported animal hides, raw wool, sick domestic animals Adult initial treatment: ciprofloxacin, 400 milligrams IV every 12 h (alternative: doxycycline, 100 milligrams IV every 12 h or levofloxacin, 500 milligrams every 24 h), + clindamycin, 900 milligrams IV every 8 h, + rifampin, 300 milligrams IV every 12 h. Plus one-time infusion raxibacumab, 40 milligrams/kg diluted over 2.25 h. When clinically stable: ciprofloxacin, 500 milligrams PO twice a day, + clindamycin, 450 milligrams PO every 8 h, + rifampin, 300 milligrams PO twice a day. Treat for 60 d. Brucellosis Brucella species Food animals and product handling, ingestion, inhalation Mild disease: doxycycline, 100 milligrams PO twice a day for 6 weeks, + gentamicin, 5 milligrams/kg IV daily for 7 d. Alternative: doxycycline, 100 milligrams PO twice a day, + rifampin, 600–900 milligrams PO daily for 6 weeks. Joint involvement: doxycycline, 100 milligrams PO twice a day, + rifampin, 600–900 milligrams PO daily for 3 months, + gentamicin, 5 milligrams/kg IV once daily for first 7 d. Neurologic involvement: doxycycline, 100 milligrams IV/PO twice a day, + rifampin, 600–900 milligrams PO daily, + ceftriaxone, 2 grams IV twice a day. Treat until cerebrospinal fluid normalizes. Psittacosis, ornithosis Chlamydophila psittaci Bird exposure—pet and pet shop, veterinarians, turkey farms Doxycycline, 100 milligrams PO for 5–7 d. Alternative: azithromycin dose pack or levofloxacin, 750 milligrams PO for 5–7 d. Q fever Coxiella burnetii Inhaled endospores from animal-contaminated soil; cat afterbirth, ticks Doxycycline, 100 milligrams PO twice a day for 2–3 weeks. Alternative: consider 2–3 weeks of a fluoroquinolone or a macrolide. Tularemia Francisella tularensis Aerosol from dead birds, animals; bacteremic spread from bubo; ticks and biting flies Adults: streptomycin, 1 gram IM/IV twice a day, or gentamicin/tobramycin, 5 milligrams/kg IV divided every 8 h. Treat for 10 d. Children: streptomycin, 15 milligrams/kg IM twice daily (should not exceed 2 grams/d). Mild disease: ciprofloxacin 750 milligrams PO twice a day or doxycycline 100 milligrams PO twice a day. Treat for 21 d. Prophylaxis for lab exposures: doxycycline 100 milligrams PO twice a day or ciprofloxacin 500 milligrams PO twice a day. Treat for 14 d. Leptospirosis Leptospira interrogans Domestic and wild animals, contaminated water, veterinarians, farmers Mild disease: doxycycline, 100 milligrams PO twice a day for 5–7 d. Alternative: azithromycin, 500 milligrams PO daily for 3 d. Severe disease: penicillin G, 1.5 million units IV every 6 h for 7 d, or ceftriaxone, 2 grams IV daily for 7 d. Alternative: doxycycline, 100 milligrams IV for 7 d. Pasteurellosis Pasteurella multocida Underlying respiratory disease; contact with cat, dog in home Amoxicillin-clavulanate, 875/125 milligrams PO twice a day for 7–10 d. Alternative therapies based on culture data and presence of Staphylococcus coinfection. Often resistant to cephalexin, clindamycin, and macrolides. Rocky Mountain spotted fever Rickettsia rickettsii Tick-associated, typical rash Doxycycline 100 milligrams PO or IV twice a day for 7 d, or for 2 d after temperature normalizes. Some recommendations exist for an initial loading dose of 200 milligrams. For children weighing <45 kg, the dose is 2.2 milligrams/kg twice daily.

Mountain spotted fever Rickettsia rickettsii Tick-associated, typical rash Doxycycline 100 milligrams PO or IV twice a day for 7 d, or for 2 d after temperature normalizes. Some recommendations exist for an initial loading dose of 200 milligrams. For children weighing <45 kg, the dose is 2.2 milligrams/kg twice daily. Although doxycycline is contraindicated for use in pregnancy, it may be warranted in life-threatening situations. Chloramphenicol is an alternative; however, it has multiple toxic effects and contraindications, and may be difficult to obtain. Dosing is 50 milligrams/kg/d divided into 4 doses for 7 d. Toxoplasmosis Toxoplasma gondii Contact with domestic food animals and pets, ingestion of cysts, pneumonia in immunocompromised persons Severe disease: Pyrimethamine, 200 milligrams PO on d 1, followed by 50–75 milligrams PO every 24 h, + sulfadiazine, 1–1.5 grams PO every 6 h, + leucovorin, 5–20 milligrams 3 times weekly. If ocular involvement, treat as above and add prednisone, 0.5 milligrams/kg PO twice a day. Treat until 1–2 weeks after symptoms resolve, continue leucovorin for 1 week past that. Plague Yersinia pestis Contact with mammals and fleas; veterinarians; outdoor activities in endemic area; cats Gentamicin, 5 milligrams/kg IV daily for 10 d. Alternative: streptomycin, 15 milligrams/kg IV/IM twice a day for 10 d. Postexposure prophylaxis: doxycycline, 100 milligrams PO twice a day, or ciprofloxacin, 500 milligrams PO twice a day for 7 d. Hantavirus pulmonary syndrome Bunyaviridae Rodent feces, urine, and saliva Extracorporeal membrane oxygenation or consideration of ribavirin Tintinalli_Sec13_p0997-1100.indd 1077 8/2/19 8:12 PM

Postexposure prophylaxis: doxycycline, 100 milligrams PO twice a day, or ciprofloxacin, 500 milligrams PO twice a day for 7 d. Hantavirus pulmonary syndrome Bunyaviridae Rodent feces, urine, and saliva Extracorporeal membrane oxygenation or consideration of ribavirin Tintinalli_Sec13_p0997-1100.indd 1077 8/2/19 8:12 PM 1078 SECTION 13: Infectious Diseases ciprofloxacin, or chloramphenicol occurs after improvement, although these agents can be used as initial therapy in those who cannot tolerate the preferred choice. Continue any therapy for at least 10 days or 2 days after resolution of fever 31 (Table 161-6). HANTAVIRUS Hantavirus, identified in 1977, is from the Sin Nombre virus, which belongs to the Bunyaviridae family of viruses. The deer mouse (Peromyscus maniculatus ) is the primary vector in the southwestern United States. 32 Infected rodents excrete hantavirus in feces, urine, and saliva. Human infection occurs with the inhalation of dried, particulate feces, by contact with urine, or by a rodent bite. In Asia, hantaviruses can cause hemorrhagic fever with renal syndrome—acute renal failure with concurrent thrombocytopenia, ocular abnormalities, and flulike symp toms. In the United States, the presentation of this zoonosis is that of a cardiopulmonary syndrome, 32 which consists of an initial flulike pro dromal illness of 3 to 4 days in duration, rapidly followed by pulmonary edema, hypoxia, hypotension, tachycardia, and metabolic acidosis. Dizziness, nausea, vomiting, absence of cough, and thrombocytopenia are common and may help to differentiate hantavirus pulmonary syndrome from acute respiratory distress syndrome, bacterial pneumonia, and influenza pneumonia. Hantavirus pulmonary syndrome carries a very high mortality rate, initially estimated around 60%, but that has now improved to 30% with efforts toward recognition and early aggressive care. 33 Diagnosis is with an immunofluorescent or immunoblot assay. Treatment is supportive.34  SELECTED DERMATOLOGIC ZOONOTIC INFECTIONS Dermatologic findings are common in zoonotic infections because the skin is often the site of inoculation. Ulcerations at the site of inoculation (chancres), typically on the hands or forearms, can result from zoonotic infection caused by bacteria, mycobacteria, fungi, or viruses. BACTERIAL AND VIRAL ZOONOTIC SKIN INFECTIONS The most well-described bacterial chancriform zoonotic lesions are B. anthracis (anthrax), B. henselae (cat-scratch disease), Erysipelothrix rhusiopathiae (erysipeloid), F. tularensis (tularemia), Listeria monocyto genes (listeriosis), Mycobacterium marinum (aquarium granuloma), and Burkholderia mallei (glanders). 35 Most chancriform zoonotic infections occur in livestock workers, cattle ranchers, veterinarians, stable workers, horse trainers, slaughterhouse workers, poultry workers, and farmers. Significant zoonotic fungal infection is principally from Blastomyces dermatitidis (cutaneous blastomycosis) and Sporothrix schenckii (sporotrichosis). Dog and cat owners, along with veterinarians, are most at risk of contracting these two fungal zoonoses. Viral zoonotic dermatoses include Vaccinia species (cowpox), Paravaccinia species (pseudocowpox), and bovine papular stomatitis. These cutaneous viral zoonoses often occur on the hands and forearms of patients who work closely with cattle, sheep, goats, or horses. Systemic zoonoses can be accompanied by a nonspecific generalized maculo papular rash, which does not facilitate the diagnosis. CUTANEOUS ANTHRAX Cutaneous anthrax, also known as woolsorter’s disease, accounts for 95% of all anthrax infections.36 Cutaneous anthrax is most common in groups dependent on and in close contact with livestock and in agriculturebased societies. Recently, localized outbreaks occurred in injection drug users.

diagnosis. CUTANEOUS ANTHRAX Cutaneous anthrax, also known as woolsorter’s disease, accounts for 95% of all anthrax infections.36 Cutaneous anthrax is most common in groups dependent on and in close contact with livestock and in agriculturebased societies. Recently, localized outbreaks occurred in injection drug users. 36 The hands and fingers are the most commonly infected areas of the body, but arms, lower legs, and feet can also be involved. After deposit of anthrax spores in a skin wound, a painless or pruritic macule develops 1 to 5 days later at the inoculum site. The macule evolves into an ulcerative site with multiple serosanguinous vesicles. Vesicles contain the anthrax bacillus and are infectious. Gram stain or culture of the vesicular fluid is often diagnostic. The ulcer progresses to a painless black eschar and falls off within 2 weeks. If purulence is present, suspect secondary bacterial superinfection. Untreated, mortality is between 5% and 20% with progression to shock possible. If the disease is acquired naturally (i.e., bioterrorism not a concern), penicillin or amoxicillin for 3 to 7 days is the primary treatment. 37 Other patients are treated with oral cipro floxacin for 60 days, with doxycycline as an alternative option.  ZOONOSES ACQUIRED FROM HOUSEHOLD PETS Dogs and cats are the two most common household pets in North America and account for the majority of these zoonotic infections. Small rodents, pet birds, reptiles, and aquarium fish account for only a fraction of the zoonotic infections in the United States 38 (Table 161-7). A growing trend of individuals owning small flocks of chickens and other poultry led to >70 outbreaks of Salmonella since 2000. 39 Although hand washing is often key to prevention, the number of outbreaks has increased as residential livestock have become more common. HELMINTHS (WORMS) Up to 50% of dogs are infected with at least one intestinal parasite, and 15% of adult dogs actively excrete Toxocara canis, the source of toxocariasis and visceral larva migrans. 38 Despite its prevalence in dogs, human toxocariasis is infrequently diagnosed, probably because infec tion is often subclinical. Typically, the only indication of infection is eosinophilia. Children may display fever, cough, nonspecific rash, and failure to thrive. Rarely, pulmonary infiltrates, hepatosplenomegaly, and seizures may occur. Diagnosis is by either biopsy of infected tissue or by enzyme-linked immunosorbent assay. Treatment in the symptomatic patient consists of albendazole or mebendazole (Table 161-5). Cortico steroids can be used to control the allergic component. Other intestinal parasites transmitted to humans from household pets include Ancylostoma caninum or braziliense (cutaneous larva migrans), Echinococcus granulosus (echinococcosis), and Dipylidium caninum (dipylidiasis or dog and cat tapeworm). Cutaneous larva migrans is often a self-limiting, pruritic, erythematous serpiginous rash caused by a migrating hookworm larva in the skin acquired from fecally contaminated soil. Single-dose ivermectin is the preferred treatment in patients over 5 years of age. Multiple-dose albendazole is another option, as is topical thiabendazole. Although dogs and other carnivores are the definitive hosts for E. granulosus, echinococcosis is most common in areas of cattle and sheep ranching. This zoonosis involves multiple organ systems: liver, lung, muscle, bone, kidney, and brain. Typically, there is a unilocular cyst containing multiple larvae that enlarge over time. Definitive treatment is surgical; however, leakage of the cystic fluid can spread the infection and cause an anaphylactic reac tion.

hing. This zoonosis involves multiple organ systems: liver, lung, muscle, bone, kidney, and brain. Typically, there is a unilocular cyst containing multiple larvae that enlarge over time. Definitive treatment is surgical; however, leakage of the cystic fluid can spread the infection and cause an anaphylactic reac tion. Should the lesion not be anatomically favorable for unruptured excision, pharmacotherapy with benzimidazoles can be used, but recurrence is high. TABLE 161-7 Pet-Associated Zoonotic Infections •   Dog: anthrax, brucellosis, campylobacteriosis, cryptosporidiosis, dipylidiasis, echinococcosis, histoplasmosis, leptospirosis, pasteurellosis, rabies, Rocky Mountain spotted fever, salmonellosis, toxocariasis, tularemia, yersiniosis •   Cat: anthrax, campylobacteriosis, cryptosporidiosis, histoplasmosis, pasteurellosis, plague, Q fever, rabies, salmonellosis, toxocariasis, tularemia •   Bird and fowl: Cryptococcus, erysipeloid, listeriosis, Mycobacterium, psittacosis/ornithosis (Chlamydophila psittaci), salmonellosis, tularemia, viral encephalitis •   Rodent: leptospirosis, listeriosis, lymphocytic choriomeningitis, murine typhus, plague, rat-bite fever (Streptobacillus moniliformis), salmonellosis, tularemia, yersiniosis •   Fish and reptiles: erysipeloid, Mycobacterium marinum, salmonellosis, Streptococcus iniae, vibriosis Tintinalli_Sec13_p0997-1100.indd 1078 8/2/19 8:12 PM