Ticks parasitize vertebrates in virtually every part of the world. Saliva of some tick species contains an anesthetic, as well as several 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, and many affected patients do not recall a history of a tick bite.1 Tickborne diseases are often accompanied by a rash. Tickborne zoonoses have a geographic distribution (Table 160–3) and seasonal variation.
Tickborne Zoonotic Infections
||Download (.pdf) Table 160–3
Tickborne Zoonotic 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 D. 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 |
|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|
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 portions of the tick because residual body parts can stimulate a granulomatous reaction and persistent infection. After complete removal of the tick, cleanse and disinfect the skin surface. Do not handle the extracted tick with bare hands. 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, with certain models having improved outcomes over the use of tweezers.2 Save the removed tick in alcohol to aid in identification, especially if illness occurs.
Prophylactic treatment of a tick bite can be given only in select, not all, circumstances.3 Recommended settings for prophylactic treatment include the ability to easily identify the tick as Ixodes scapularis, tick attachment for greater than 36 hours or with obvious tick engorgement, and a local tick bite in an area with Borrelia burgdorferi carrier rate of greater than 20%.4 In these cases, use a one-time dose of doxycycline 200 milligrams for adults or 4 milligrams/kg in children for Lyme 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 according 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 (RMSF) is one of the most severe of the tickborne illnesses in the United States, with peak occurrence occurring in June and July. The fatality rate for RMSF is currently less than 0.5%. Geographically, although reported widely and in both rural and urban settings any time of the year, more than 60% of reported cases originate from five states: North Carolina, Tennessee, Oklahoma, Missouri, and Arkansas.5 The causative organism of RMSF is Rickettsia rickettsii, a pleomorphic, obligate intracellular organism, and the vectors in the United States 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 are implicated in causing cases of possible RMSF and may be responsible for an increase in incidence as more cases are reported.
The diagnosis relies on epidemiologic features and the clinical exclusion of other diseases. Early signs and symptoms of RMSF 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 the patients can recall a tick bite.
The rash occurs on days 2 to 4 after the onset of fever but is absent in about 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 maculopapular rash begins on the hands, feet, wrists, and ankles, and then spreads centripetally up the trunk (see chapter 249, "Generalized Skin Disorders"). 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 recognize 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.6
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 aminotransferase and alanine aminotransferase), and hyponatremia suggests RMSF, especially if the disease is advanced. Hypoalbuminemia may be present and is the cause of edema.6 In addition to clinical patterns, diagnosis can be confirmed with a rise in antibody titer between acute and convalescent serum, skin biopsy with immunofluorescent testing, or culture, although none of these are useful for ED diagnosis.
Preferred treatment is doxycycline (Table 160–4). Given the relatively 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. Doxycycline therapy is recommended by the American Academy of Pediatrics and by the Centers for Disease Control and Prevention as the treatment of choice for all rickettsial diseases, including RMSF, in children of all ages.1
Tickborne Zoonotic Infections and Specific Treatment
||Download (.pdf) Table 160–4
Tickborne Zoonotic Infections and Specific Treatment
|Tickborne 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.
|Tickborne 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 alternate.
|Colorado tick fever ||Treatment is supportive. |
|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.
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 250–1000 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.|
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. Diagnosis is made upon finding a tick on the body. Tick removal leads to recovery in 24 hours.
Lyme disease was probably first noted in Europe about 100 years ago, based on descriptions of the rash, erythema chronicum migrans. Lyme disease is the most common vectorborne zoonotic infection in the United States, with approximately 30,000 cases reported annually. 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.7 Lyme disease is reported in Europe, China, Japan, Australia, parts of Russia, and in all U.S. continental states, with 95% of the reported cases originating from just 13 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 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 less than 36 hours.4,8
Lyme disease has three stages. The first stage is local and often characterized by erythema migrans: an erythematous plaque with central clearing. Erythema migrans develops 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 also be nonspecific symptoms of fever, chills, fatigue, myalgias, arthralgias, and lymphadenopathy. 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, depending on skin location, may go unnoticed by the patient.
The second stage, early disseminated disease, develops with the reproduction and spread of the Borrelia spirochete and occurs within a few days to months of the initial infection. This stage is characterized by 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 secondary 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, myocarditis, 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 can have persistent symptoms of disease, usually muscle and joint aches with fatigue. This entity is currently being studied but seems to be an autoimmune response persistent from the initial infection.
Diagnosis is clinical early in disease when erythema migrans is present; testing is required to diagnose 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 persistent other manifestations require ceftriaxone therapy (Table 160–4). A previously marketed vaccine no longer exists, because it conferred no ongoing immunity.
Ehrlichiosis is a group of zoonotic diseases caused by the Ehrlichia genus, gram-negative pleomorphic coccobacilli that 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 has been on the rise, increasing from 0.8 to 3 cases/million in the United States in 2000 to 2007, partly attributed to increased recognition. It has also been described in Europe. The mortality rate in confirmed cases varies between 1% and 3% depending on causative agent.10
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 majority of cases (97%). Rash is present in 30% of adults and has no pathognomonic features, making it a nonspecific diagnostic clue.12 With disease progression, a minority of patients go on to develop severe complications of renal failure, respiratory failure, and encephalitis. The acute phase of illness lasts less than 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 is made clinically but can be confirmed by laboratory testing once treatment has begun. Peripheral blood smear may show colonies of ehrlichiae in the white blood cells in 20% of infected patients. Polymerase chain reaction is specific but not sensitive and is best in the first week of illness. Antibody tests are expected to be negative in 85% of patients during initial infection. The gold standard test is immunofluorescence assay.11
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 used in those with contraindications to doxycycline.12
Anaplasmosis is a tickborne 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 black-legged tick, I. scapularis, as well as the western black-legged tick, Ixodes pacificus. The zoonotic reservoirs are deer, elk, and rodents, and the disease is prevalent in the upper midwestern and northeastern United States in the same areas where Lyme disease is present, with 90% of all reported anaplasmosis cases from only six states. Peak transmission occurs in the summer, specifically June and July. Incidence of reported cases has risen from 1.4 to 6.1 cases per million in the United States from 2000 to 2010. Case mortality rate has remained less than 1%.14 Symptoms, developing within 1 to 2 weeks of the initial bite, are nonspecific and similar to those of ehrlichiosis or influenza—fever, chills, headache, and myalgias. Rash is rare in anaplasmosis and should clue the clinician to consider an alternative diagnosis.14 Laboratory findings are nonspecific and should not alter the clinical decision to treat but may consist of leukocytopenia, thrombocytopenia, and elevation of hepatic enzymes. Confirmatory testing modalities are similar to those for ehrlichiosis. Treatment is with doxycycline, as noted in other tick infections (Table 160–4).
TICKBORNE RELAPSING FEVER
Relapsing fever is caused by several varieties of gram-negative Borrelia spirochetes. It was first described in West Africa and is now recognized worldwide. Within the United States, it is rarely found east of Texas.15 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.16 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 over 90% of cases.16 Characteristically, the roughly 3-day-long febrile episodes are interspersed with 7-day-long afebrile periods, which may cycle one to four times before resolution.16 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 is confirmed with the appearance of spirochetes on darkfield 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.16
The recommended treatment is with tetracycline or erythromycin. Use IV ceftriaxone for 10 to 14 days if any CNS involvement is seen.16 Similar to Lyme disease, patients in an endemic area with a confirmed tick bite can receive postexposure doxycycline as effective prophylaxis.17
Colorado tick fever is caused by an RNA virus of the genus Coltivirus in the family Reoviridae.18 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 and is limited to 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 is characterized by fever, chills, headache, myalgias, 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 is most often based on history, clinical findings, and geography. Treatment is supportive.18
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.18 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,18 and is characterized by 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 is noted to have 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 disease.
Laboratory findings are nonspecific; 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. Clinical suspicion should be high for this disease in endemic areas. Due to the ease of transmission and lethality, F. tularensis is a possible agent of biologic warfare/terrorism (Table 160–4).
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.19 The major zoonotic reservoirs are domesticated mammals, rodents, and deer. Ixodes ticks function as the principal vector globally. Babesiosis has been transmitted through blood transfusions and is the most common transmitted pathogen reported to the Food and Drug Association, with about 160 cases reported since 1979.19 Clinically, the presentation occurs 1 to 4 weeks after exposure with 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. Co-infection 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 is made by finding intraerythrocytic ring forms resembling 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 160–4).