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Am Fam Physician. 2007;76(1):137-139

Guideline source: Centers for Disease Control and Prevention

Literature search described? No

Evidence rating system used? No

Published source: Morbidity and Mortality Weekly Report, March 31, 2006

Although antimicrobial therapy is widely available, tick-borne rickettsial diseases cause severe morbidity and mortality in otherwise healthy Americans. The diseases most common in the United States include Rocky Mountain spotted fever (RMSF), human monocytic ehrlichiosis (HME), human granulocytic anaplasmosis (HGA), and Ehrlichia ewingii infection. The most difficult challenge is making diagnoses early, when antibiotics are most effective.


Tick-borne rickettsial diseases are caused by pathogens acquired from hard-bodied ticks. The epidemiology of these diseases is related to seasonal and geographic factors. The diseases are most common during the warmer months of spring and summer, when ticks are most likely to feed on humans; however, these diseases may occur any time of year. RMSF and HME are most common in southeastern and south central states, although RMSF is widespread throughout the United States. HGA is most common in New England, north central states, and certain areas on the West Coast. Although the etiology of E. ewingii infection is unclear, it has been reported in south Atlantic and south central states and in isolated areas of New England. Table 1 lists the features of tick-borne rickettsial diseases.

Disease (causative agent)Primary vector(s)Approximate distributionIncubation period (days)Common initial signs and symptomsCommon laboratory abnormalitiesRashFatality rate (%)
Rocky Mountain Spotted fever (Rickettsia rickettsii)American dog tick (Dermacentor variabilis), Rocky Mountain wood tick (Dermacentor andersoni), brown dog tick (Rhipicephalus sanguineus) in ArizonaWidespread in the United States, especially in south Atlantic and south central statesTwo to 14Fever, nausea, vomiting, myalgia, anorexia, headacheThrombocytopenia, mild hyponatremia, mildly elevated hepatic transaminase levelsMaculopapular rash appears approximately two to four days after fever onset in 50 to 80 percent of adults and in more than 90 percent of children; may involve the palms and soles5 to 10
Human monocytic ehrlichiosis (Ehrlichia chaffeensis)Lone star tick (Amblyomma americanum)Southern, south central, mid-Atlantic, and northern states; isolated areas of New EnglandFive to 14Fever, headache, malaise, myalgiaLeukopenia, thrombocytopenia, elevated serum transaminase levelsRash appears in less than 30 percent of adults and in about 60 percent of children2 to 3
Human granulocytic anaplasmosis (Anaplasma phagocytophilum)Black-legged tick (Ixodes scapularis and Ixodes pacificus) in the United StatesNorth central and Pacific states; New EnglandFive to 21Fever, headache, malaise, nausea, vomitingLeukopenia, thrombocytopenia, elevated serum transaminase levelsRareLess than 1
Ehrlichia ewingii InfectionLone star tickSouth Atlantic and south central states; isolated areas of New EnglandFive to 14Fever, headache, myalgia, nausea, vomitingLeukopenia, thrombocytopenia, elevated serum transaminase levelsRareNone documented


Early diagnosis is difficult because early signs and symptoms usually are nonspecific or mimic benign viral illnesses. However, some clinical clues can help physicians detect early tick-borne rickettsial disease and differentiate it from similar illnesses.


A thorough clinical history should include questions about tick bites, recent exposure to tick habitats, recent travel, and similar illness in close contacts and pets. The history can help physicians determine a likely diagnosis, although the absence of these features does not rule out tick-borne illness.

Outdoor recreational or occupational activities can increase the risk of tick-borne rickettsial diseases, particularly from April to September and if the activity takes place near high vegetation (e.g., camping, hiking, gardening). Persons in frequent contact with animals and those who have pets with a history of tick bites also are at increased risk. Patients may not report a specific personal history of tick bite because most do not realize they have been bitten; bite marks may be difficult to detect or distinguish from other bites (e.g., spider or chigger bites). Persons who live in endemic areas (e.g., south Atlantic, north central, south central, and New England states) are at risk even in their own backyards and neighborhoods.

It is important to ask patients if they have recently traveled to endemic areas. Patients who have traveled to international destinations such as the southern Mediterranean, Central and South America, Africa, Asia, and the Middle East may have acquired a tick-borne rickettsial disease not seen in the United States, especially if the patient visited rural or outdoor areas.

Tick-borne pathogens can cause clusters of illness among persons who have spent time in the same location. Therefore, patients should be questioned about similar illness in family members, coworkers, and community members.


Most tick-borne rickettsial diseases cause sudden fever, chills, and headache (possibly severe). These symptoms commonly are associated with malaise and myalgia. Nausea, vomiting, and anorexia are common in early illness, especially with RMSF and HME. Children with RMSF or HME may have abdominal pain, altered mental status, and conjunctival infection. Rare symptoms include severe abdominal pain and meningoencephalitis. Rash is common with RMSF, but it is less common with HME and rare with HGA or E. ewingii infection. Clinically, tick-borne rickettsial diseases are difficult to differentiate from other diseases.

The rash associated with RMSF usually appears two to four days after onset of fever, and typically presents as small, blanching, pink macules on the ankles, wrists, or forearms that evolve into maculopapules. It can spread throughout the body, including to the palms and soles, but the face usually is not affected. One half of patients develop petechiae, often with severe illness. The progression of the rash is variable and may be difficult to discern. Other causes of fever and maculopapular or petechial rash include murine typhus, monocytotropic ehrlichiosis, group A streptococcal pharyngitis, erythema infectiosum (fifth disease), roseola, and enteroviral infection. The rash's dermatologic classification, distribution, pattern, and timing of onset can help rule out other exanthemata.


Patients with suspected tick-borne rickettsial disease should receive a complete blood count, comprehensive metabolic panel, and peripheral blood smear. Thrombocytopenia and hyponatremia suggest RMSF; and leukopenia, thrombocytopenia, and modest elevations of liver transaminase levels suggest HME and HGA. Blood tests may help detect HGA and E. ewingii infections. However, the absence of these results does not necessarily rule out tick-borne rickettsial disease.


Assessing a patient's symptoms and signs, clinical history, and laboratory test results can help guide decisions regarding the treatment of tick-borne rickettsial disease, although treatment should not be delayed while awaiting laboratory confirmation.

Outpatient monitoring for 24 to 48 hours may be considered for patients in the early course of illness who have a nonspecific history and physician examination and normal laboratory test results. If tick-borne rickettsial disease is suspected, antibiotic treatment should be initiated. Prophylactic antibiotic therapy is not indicated for patients without recent tick bites or who are not ill.

Doxycycline (Vibramycin) is the antibiotic of choice for adults and children. Doxycycline is contraindicated in pregnant women, although it may be considered in life-threatening situations when clinical suspicion of tick-borne illness is high. The recommended dosage of doxycycline is 100 mg orally or intravenously twice a day for adults, and 2.2 mg per kg orally or intravenously twice a day for children who weigh less than 100 lb (45.4 kg). Although the optimal duration of therapy has not been established, a five- to seven-day course is recommended for RMSF and HME after the fever subsides. A 10- to 14-day course is recommended for HGA. Chloramphenicol (Chloromycetin) may be used as an alternative to doxycycline; however, this drug may cause side effects, and monitoring of blood indices may be needed.

Early symptoms of invasive meningococcal infection overlap with those of tick-borne rickettsial disease. Therefore, if meningococcal infection cannot be ruled out, physicians should add a parenteral penicillin or cephalosporin that is active against Neisseria meningitidis to doxycycline therapy.

Coverage of guidelines from other organizations does not imply endorsement by AFP or the AAFP.

This series is coordinated by Michael J. Arnold, MD, associate medical editor.

A collection of Practice Guidelines published in AFP is available at

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