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Tick-Borne Illnesses

Choi, Edwin MD; Pyzocha, Natasha J. DO; Maurer, Douglas M. DO

doi: 10.1249/JSR.0000000000000238
Environmental Conditions: Section Articles
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Tick-borne diseases are prevalent throughout the United States. These illnesses are caused by a variety of different pathogens that use ticks as vectors, including bacteria, viruses, rickettsia, and protozoa. Some of the most common illnesses caused by ticks are Lyme disease, Rocky Mountain spotted fever, babesiosis, ehrlichiosis, anaplasmosis, tularemia, Colorado tick fever, tick-borne relapsing fever, and Powassan disease. Unique skin changes, fever, and influenza-like symptoms may indicate tick-borne disease. Early diagnosis can be difficult as well as nonspecific and can resemble overtraining syndrome. Diagnosis is important to facilitate early treatment to decrease morbidity and mortality and should often be initiated before a definitive diagnosis is made. Treatment guidelines are published by the Centers for Disease Control and Prevention. As tick-borne diseases increase and their geographic regions expand, it is important for providers to distinguish the often overlapping and diverse presentations of these diseases.

Madigan Army Medical Center, Department of Family Medicine, Fort Lewis, WA

Address for correspondence: Douglas M. Maurer, DO, MPH, FAAFP, Department of Family Medicine, Madigan Army Medical Center, 9040 Fitzsimmons Avenue, Fort Lewis, WA 98431; E-mail: Douglas.m.maurer.mil@mail.mil.

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Introduction

Ticks are the most common arthropod vectors of disease in the United States and the second most common vector worldwide. With athletes commonly participating in outdoor activities, ticks are a common source of disease. Many athletes are dog owners who frequently involve their dogs in outdoor activities. Dog owners are five times more likely to contract Rocky Mountain spotted fever (RMSF) than non-dog owners (20). Several tick-borne diseases can also be transmitted via blood transfusions (36). Ticks can carry and transmit multiple infectious pathogens including bacteria, virus, and protozoans. Many have been found to have multiple infectious organisms simultaneously. The ease of geographic travel has allowed tick species to travel globally, attached to people, their pets, and other cargo. Although certain diseases are typically seen in specific regions, they can be theoretically present anywhere in the world (36). Seven ticks are commonly found throughout the United States (Figure 1), and each can transmit similar but different illnesses (Table).

Table

Table

Figure 1

Figure 1

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Lyme Disease

Epidemiology

Lyme disease, also known as erythema chronicum migrans, is the most common vector-borne infectious disease in the United States (27). It is caused by the spirochete Borrelia and transmitted by the black-legged tick (or deer tick) or the western black-legged tick. Incidence has increased recently with 38,468 cases reported in 2009 (11). All ages may be infected, but peak cases are seen in children 5 to 14 years and adults from 50 to 59 years of age (36). The majority of cases occur during summer. Transmission is associated with longer attachment periods of at least 48 to 72 h (28).

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Stage I

Stage I begins as a localized infection with findings including fevers, malaise, local lymphadenopathy, and myalgias. It usually occurs 7 to 10 d after the tick bite. Approximately 75% of patients develop erythema migrans near or at the site of the tick bite, which is described as a classic rash of central erythema with central clearing or central purpura (bull’s eye rash). The rash is usually warm to the touch and can be pruritic or painful. Erythema migrans usually fades after 3 to 4 wk without treatment. Antibiotic treatment reduces duration to several days. However, untreated patients are at a higher risk of progressing to stage II or stage III (36). Image of the typical target rash can be found at http://www.cdc.gov/ticks/images/target_lesion.jpg.

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Stage II

Stage II occurs days to weeks after the initial infection when spirochetes have disseminated from the skin to the bloodstream or lymphatic system. Disseminated erythema migrans is the most common presentation of stage II disease, and secondary lesions are usually smaller and may lack central clearing. The rash spares the palms and soles, and there is no blistering or mucosal involvement (33). Neurologic syndromes occur in 10% to 40% of patients and include meningitis, encephalitis, and meningoencephalitis (36). The most common symptoms are lethargy, forgetfulness, disorientation, somnolence, dizziness, photophobia, and incoordination. Paralysis of the facial nerve may occur and persist for several months but usually resolves spontaneously (36). Radiculoneuritis or mononeuritis multiplex also may occur. Lumbar puncture typically shows pleocytosis (less than 1,000 cells·mm−3), with lymphocyte predominance and high protein levels. Ten percent of patients may develop gastrointestinal symptoms of hepatitis, hepatomegaly, and generalized abdominal pain. This usually resolves spontaneously in less than 1 wk but may persist for several weeks (21). Cardiac symptoms may develop in 10% of patients (31). Cardiac involvement is usually self-limited (1 to 2 wk) and rarely life threatening; however, temporary interventions of transvenous pacing may be required or permanent pacemaker implantation may be needed (17). The most common cardiac manifestation of Lyme disease is conduction delay at the AV node (23,26). If a complete heart block occurs, cardiac biopsy can reveal presence of spirochetes. Cardiac magnetic resonance imaging (MRI) can be used to evaluate response to antibiotics (13,18). Patients with a first-degree atrioventricular block and a PR interval exceeding 300 ms, as well as all patients with second- and third-degree heart blocks, should be admitted for observation and antibiotic treatment. Patients with a third-degree heart block require temporary transvenous pacing and may require permanent pacemaker implantation (2). Monoarticular arthritis develops in 60% of patients and may persist for months (12,35). Joint swelling is common only in the knee, often with chronic effusions. Synovial fluid of involved joints demonstrates a median white blood cell count of 25,000 mm−3, with polymorphonuclear leukocyte predominance. Polymerase chain reaction (PCR) testing of synovial fluid is positive in 85% of cases of Lyme arthritis (24).

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Stage III

Stage III of Lyme disease presents about a year or more after the initial presentation and includes chronic persistent symptoms that involve multiple organ systems. Rheumatologic manifestations occur in 50% of patients, with 10% demonstrating radiographic signs of degenerative arthritis, or joint effusions. Rheumatologic workup including erythrocyte sedimentation rate (ESR); C-reactive protein (CRP); antinuclear antibodies (ANA), and rheumatoid factor will typically be negative (36). Neurologic symptoms present months to years after the initial infection. The most common presentations are progressive encephalomyelitis with ataxia, cognitive impairment, spastic paresis, and involvement of cranial nerves VII and VIII (36). Lumbar puncture reveals lymphocytic pleocytosis and anti-Borrelia burgdorferi antibodies. MRI of the brain often demonstrates white matter changes consistent with encephalopathy (36).

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Diagnosis

Lyme disease is a clinical diagnosis based on a history of possible exposure to infected ticks and signs or symptoms. Laboratory tests may be helpful if used correctly but generally confirm or rule out the presence of disease. The Centers for Disease Control and Prevention (CDC) currently recommends a two-step blood test to diagnose Lyme disease. The first step tests enzyme immunoassay (EIA); if negative, no further testing of the specimen is recommended. If the first step is positive or indeterminate (equivocal), the second step or an immunoblot test (IFA/Western blot) should be completed. Results are considered diagnostic only if both the EIA/IFA and the immunoblot are positive (12).

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Treatment

The risk of Lyme disease is low if the tick was attached for less than 36 h. The Infectious Diseases Society of America does not recommend antimicrobial prophylaxis or serologic testing for recognized tick bites (E-III). A single dose of doxycycline may be offered to adult patients (200 mg) and to children 8 years of age (4 mg·kg−1, up to a maximum dose of 200 mg) (B-I) when the attached tick can be reliably identified as an adult or nymphal Ixodes scapularis tick attached for 36 h. Prophylaxis can be started within 72 h of the time that the tick was removed (4). During the first 24 h of antibiotic therapy, 15% of patients may develop the Jarisch-Herxheimer reaction (JHR), which presents as a rise in temperature, vasodilation, and hypotension (21). Normal saline IV and acetaminophen with initial antibiotic administration may help reduce the incidence of JHR (36).

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RMSF

Epidemiology

RMSF is also known as tick typhus, Tobia fever, São Paulo fever, fiebre maculosa, and fiebre manchada. It is caused by Rickettsia rickettsia and transmitted by the wood tick, Dermacentor andersoni, in the western United States and the dog tick, Dermacentor variabilis, in the eastern and southern regions of the United States. It is the most common rickettsial disease in the United States and occurs in all states except Maine, Hawaii, and Alaska (36). Most cases occur between April and September. Children 5 to 9 years old have the highest incidence rates (38). Six hours of tick attachment can cause inoculation (19). Humans commonly contract the disease after improperly removing ticks off their dogs when the body contents are crushed (36). Mortality can be as high as 30%, but antibiotic treatment reduces this to 3% to 5% (3).

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Signs and Symptoms

Symptoms occur 5 to 7 d after inoculation, with 85% of individuals recalling tick exposure (36). Classic presenting symptoms include sudden onset of headache, fever, chills, and rashes. Skin lesions (typically blanching pink, 2- to 5-mm macules) begin on the palms, soles, wrists, ankles, and forearms and then spread proximally. The lesions may evolve into more pronounced red lesions that can become petechial and dark red to black. Occasionally, lesions coalesce into ecchymosis with necrosis in the fingertips, toes, nose, and genitalia. Major complications of RMSF result from direct vasculitic injury. In late stages of disease, increased capillary permeability can lead to hypovolemia and shock. Severe disease may present with disseminated intravascular coagulation (DIC), acute renal failure, metabolic acidosis, cardiac and respiratory dysfunction, and neurologic compromise (36). Image of the typical petechial rash can be found at http://www.cdc.gov/ticks/images/petechial_rash.jpg.

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Diagnosis

The diagnosis of RMSF is primarily clinical. If a rash is present, skin biopsy and immunofluorescent staining for Rickettsia are 70% to 90% sensitive and 100% specific (5). After 10 d of symptoms, elevation of a specific enzyme-linked immunosorbent assay and latex agglutination titers should be used to confirm the diagnosis (5).

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Treatment

If there is clinical suspicion for RMSF, treatment should be initiated as soon as possible. Treatment is most effective at preventing death if doxycycline is started within 5 d of symptoms. Doxycycline is the treatment of choice for adults and children with dosages of 100 mg every 12 h and 2.2 mg·kg−1 twice a day for children less than 45 kg (100 lbs), respectively, at least 3 d after the fever subsides and there is evidence of clinical improvement. Standard duration of treatment is 7 to 14 d (5). Corticosteroids may be of benefit in cases of severe vasculitis or encephalitis (39).

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Ehrlichiosis and Anaplasmosis

Epidemiology

Two forms of ehrlichiosis affect humans. The first is human monocytic ehrlichiosis (HME), caused by Ehrlichia chaffeensis and transmitted by the lone star tick, Amblyomma americanum (28). Although HME occurs worldwide, transmission is highest in the southeastern United States with 70% of cases reported between May and July (15,16,29). The second form is human granulocytic ehrlichiosis, caused by the bacteria Anaplasma phagocytophilum. It is now more commonly referred to as anaplasmosis. The primary vectors are I. scapularis and D. variabilis. Anaplasmosis occurs in the upper midwestern and northeastern United States (36). Up to 60% to 70% of cases of ehrlichiosis require hospitalization (15,30).

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Signs and Symptoms

For both HME and anaplasmosis, the incubation period is 1 to 2 wk. They present similarly with a prodromal phase characterized by malaise, back pain, gastrointestinal symptoms, and fever up to 39°C. HME typically affects adults, whereas children exhibit mild symptoms. Symptoms include fever, headache, myalgias, nausea, arthralgias, cough or dyspnea, and malaise. Rashes are more common in HME than in anaplasmosis. If rashes are present with anaplasmosis, coinfection with other tick-borne diseases should be suspected (6,7). Ehrlichiosis can have neurologic complications, the most common being meningoencephalitis. Hematologic complications in HME include bone marrow, hepatic granuloma, and multiorgan perivascular lymphohistiocytic infiltrates. With anaplasmosis, opportunistic fungal and viral infections can occur. Severe cases result in renal failure, pancytopenia, DIC, acute respiratory distress syndrome (ARDS), hepatic failure, profound hypotension, and death (6,7). The rash may resemble that of RMSF (7).

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Diagnosis

Diagnosis of ehrlichiosis should be considered if clinical symptoms are present. Routine tests may show thrombocytopenia, leukopenia, or elevated liver enzyme levels. Confirmatory testing uses a PCR assay during the acute phase of illness and is most sensitive in the first week of illness. Peripheral blood smears may reveal morulae in white blood cells in up to 20% of patients. E. chaffeensis most commonly infects monocytes, whereas Ehrlichia ewingii more commonly infects granulocytes. The gold standard for both pathogens was to conduct serologic testing with IFA for IgG, with a four-fold rise in antibody titers. Ehrlichiosis is tested for E. chaffeensis, whereas anaplasmosis is tested for an A. phagocytophilum antigen (6,7).

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Treatment

Whenever either pathogen is suspected, doxycycline should be initiated immediately for adults and children. Adults should be treated with doxycycline 100 mg every 12 h and children less than 45 kg (100 lbs) treated with 2.2 mg·kg−1 body weight twice daily for 7 to 14 d or 3 d until after fever subsides. If the patient is treated within the first 5 d of the disease, fever generally subsides within 24 to 72 h. Some patients may continue to experience headache, weakness, and malaise for weeks after adequate treatment (6,7).

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Babesiosis

Epidemiology

Babesiosis is caused by the protozoan Babesia divergens or Babesia microti and transmitted by various species of Ixodes ticks. Incidence is highest from May through September, with most cases occurring in the northeastern United States (2). Risk factors for severe babesiosis include asplenia, advanced age, and other causes of impaired immune function (e.g., HIV, malignancy, and corticosteroid therapy) (8).

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Signs and Symptoms

Symptoms present approximately 1 wk after inoculation and are similar to those of influenza. In children and young adults, infections are often self-limited or asymptomatic. The disease is more severe in older adults and those with chronic medical conditions, and may include marked thrombocytopenia, DIC, hemodynamic instability, acute respiratory distress, myocardial infarction, renal failure, hepatic failure, altered mental status, and death (8). Symptoms also can present 6 to 9 wk after blood transfusion (36).

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Diagnosis

Babesiosis should be suspected in individuals with unexplained fever, history of a tick bite, or summer travel to an endemic region. Definitive diagnosis is made by Giemsa-stained blood smears. Smears may need to be repeated because of low parasitemia in individuals with intact spleens. Blood smears reveal Maltese cross appearances. PCR testing and serologic testing are alternatives to diagnosis (2).

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Treatment

Most infections can be treated symptomatically. For ill patients, 7 to 10 d of atovaquone 750 mg oral twice daily and azithromycin 500 to 1,000 mg oral are the treatment of choice. For severe cases, clindamycin 600 mg oral three times a day or 300 to 600 mg intravenously four times a day and quinine 650 mg oral three times a day for 7 to 10 d are recommended. Immunocompromised patients should complete 6 wk of antimicrobial therapy (8).

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Colorado Tick Fever

Epidemiology

Colorado tick fever (also known as mountain tick fever or mountain fever) is caused by the RNA Orbivirus. The primary vector is D. andersoni (wood tick). Colorado tick fever is found predominantly in the Rocky Mountain region and southwest Canada at elevations of 4,000 to 10,000 ft (37). In North America, 200 to 400 cases are reported each year and may be underreported secondary to vague symptoms (25). Although rare, the virus also can be transmitted from person to person via blood transfusion (37).

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Signs and Symptoms

Colorado tick fever often presents as a benign influenza-like illness, which often goes undetected. The incubation period is approximately 1 to 14 d. The most significant feature of Colorado tick fever is the biphasic or “saddleback” fever present in about 50% of patients. Symptoms remit after 2 to 4 d, but then recur 1 to 3 d later. Occasionally, symptoms of meningitis, rash, and conjunctivitis occur.

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Diagnosis

Colorado tick fever is best diagnosed via blood cultures and reverse transcriptase PCR during the first 2 wk of the illness (37). Blood smears also have been used for diagnosis using immunofluorescence staining for IgM antibodies, but these usually are not present until 14 to 21 d after illness onset. Laboratory abnormalities may include leukopenia or thrombocytopenia.

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Treatment

Treatment for Colorado tick fever is supportive. Patients with confirmed Colorado tick fever should defer blood and bone marrow donation for at least 6 months after recovery (37).

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Tularemia

Epidemiology

Tularemia is caused by the bacterium Francisella tularensis. It is transmitted by ingestion, inoculation, inhalation, or contamination and carried by ticks, deer flies, and horse flies. Consumption of undercooked infected meat and contaminated water also can transmit the disease. It is also known as rabbit fever because of its transmission through microlesions in the skin of hunters who have skinned infected rabbits. It is endemic throughout the United States, with the exception of Hawaii, being most prevalent in the southeastern and south-central United States (37). Tularemia is transmitted by the tick vector A. americanum (lone star tick) and D. variabilis (dog tick). The disease also is prevalent in the west and transmitted via the tick vector D. andersoni (wood tick) (36).

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Signs and Symptoms

The signs and symptoms of tularemia depend on a number of factors, including the portal of entry and various syndromes that may be present. In general, tularemia has a 3- to 5-d incubation period. Tularemia presents with rapid onset fever, chills, headache, malaise, fatigue, nausea, and vomiting, and myalgias often occur. A cough is also present in one third of patients. Other symptoms may include skin ulcers, sore throat, pleural effusions, pneumonia, acute respiratory distress syndrome, and pericarditis. Regional lymphadenopathy may suppurate and drain concurrently. Image of the ulcerative rash can be found at http://www.cdc.gov/ticks/images/tularemia_ulcer.jpg.

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Diagnosis

Diagnosis of tularemia is primarily clinical and if there is any suspicion of exposure to rabbits, wild rodents, or ticks. A primary pustular lesion on an extremity also may aid in diagnosis. Materials cultured from skin lesions, infected lymph nodes, or sputum can be used for acute and convalescent titers. Caution should be taken when obtaining these cultures because of the highly infectious nature of the organism. Occasionally, leukocytosis is present. Chest radiography may show a triad of oval opacities, hilar adenopathy, and pleural effusions.

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Treatment

Treatment for tularemia should begin before confirmatory laboratory tests are obtained. Consultation with an infectious disease specialist for the most current treatment guidelines or individual patient treatment decisions should be obtained because no randomized trials or evidence-based guidelines have revealed an optimal treatment (22). For severe cases in adults with tularemia, streptomycin 1 g intramuscularly every 12 h for 10 d is recommended by the CDC (36).

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Powassan Disease

Epidemiology

Powassan disease (POW) is caused by the Powassan virus. This disease spans the United States (northeastern and Great Lakes region), Canada, and Russia. Approximately 60 cases of POW were reported in the United States over the past 10 years (9).

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Signs and Symptoms

The incubation period for POW is 1 to 4 wk. Symptoms include fever, headache, vomiting, and generalized weakness. POW may progress to meningoencephalitis, classified by possible meningeal signs, altered mental status, seizures, aphasia, paresis, movement disorders, and cranial nerve palsies.

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Diagnosis

There are no commercially available tests for POW (37). Testing is available through the CDC and selected state health departments. Initial cerebrospinal fluid analysis may reveal lymphocytic pleocytosis, normal or mildly elevated protein, and normal glucose. After consultation with an infectious disease provider, measurement of virus-specific IgM antibodies in serum or cerebrospinal fluid may be considered. With this test, however, there is cross-reaction with other flaviviruses (West Nile, dengue, St. Louis virus) so false positives may occur (37). In the case of a positive immunoglobulin test, plaque reduction neutralization tests should be performed to confirm the diagnosis.

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Treatment

There is no specific antiviral treatment for POW; care is supportive.

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Tick-borne Relapsing Fever

Epidemiology

Tick-borne relapsing fever (TBRF) is caused by spirochetes of the Borrelia spp. Soft ticks of the Ornithodoros genus are the chief vectors, and the primary hosts include rodents, rabbits, and hares. Most cases occur west of the Mississippi river, in mountainous areas (2).

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Signs and Symptoms

The incubation period is approximately 7 d followed by recurring febrile episodes lasting for around 3 d. Symptoms include arthralgias, dizziness, nausea, vomiting, and high fever (greater than 40°C or 104°F and irregular in pattern). Splenomegaly, meningeal signs, epistaxis, hemoptysis, iridocyclitis, coma, cranial nerve palsy, pneumonitis, and myocarditis also can be seen.

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Diagnosis

Diagnosis of TBRF is made by smears of blood, bone marrow, or cerebrospinal fluid obtained when the patient is febrile (2). Laboratory abnormalities may include leukocytosis, thrombocytopenia, increased serum bilirubin, increased erythrocyte sedimentation rate, prolonged prothrombin time, and increased partial thromboplastin time.

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Treatment

Treatment for TBRF is oral tetracycline, 500 mg every 6 h for 10 d for adults. If tetracyclines are contraindicated, oral erythromycin 500 mg every 6 h for 10 d is recommended (37). For CNS involvement, treatment with ceftriaxone 2 g·d−1 for 10 to 14 d is the preferred treatment regimen (37). Antibiotic treatment may result in a JHR.

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Conclusion

Tick-borne diseases are found across the United States. Many different ticks serve as vectors for the spread of disease. The same tick may harbor multiple infectious pathogens, and combined infections can occur. Prevention of tick bites and rapid removal of any attached tick should be encouraged.

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Prevention

To prevent tick bites, individuals should wear proper clothing. Examples include wearing light colors (so ticks are easier to spot), boots, and tucked clothing to prevent exposed skin. Avoiding tick-infested areas, especially during the summer, also helps in preventing bites. Using tick repellants containing N,N-diethyl-m-toluamide (at least 20% concentration) for the skin and permethrin for clothing helps deter ticks from attaching (37).

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Removal of Ticks

Removing ticks as soon as possible helps prevent disease. For many ticks, it takes at least 24 to 48 h of attachment to the host before infection occurs (1). If a tick is attached to the skin, there are several techniques that can be used effectively to remove it, including forceps and commercial devices.

Using forceps, the tick’s body should be grasped as close to the skin as possible and vertical traction applied until it is dislodged. Do not twist or jerk the tick because this can cause mouthparts to break off and remain in the skin. If this happens, remove the mouthparts with a set of clean forceps. Commercial devices also are available for tick removal. Removal methods not recommended include using petroleum jelly, lighted matches, cigarettes, alcohol, gasoline, or fingernail polish, as any method that attempts to disrupt or suffocate the tick leads to an increased chance of regurgitation of the infected material into the body or formulation of a granuloma (2). To remove larval ticks, a piece of tape should be placed over the tick, or a credit card (or thick nonpliable comparable card) should be scraped along the skin. Clothes also should be laundered in hot water and dried using high heat for 1 h because of possible larvae on other parts of the body or clothes. After removing any tick, thoroughly clean the bite area and hands with an antiseptic or soap and water. Image of an example of tick removal can be found at http://www.cdc.gov/ticks/removing_a_tick.html.

The opinions and assertions expressed herein are those of the authors and are not to be construed as reflecting the views of the Department of Defense or the U.S. Government.

The authors declare no conflict of interest and do not have any financial disclosures.

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