TICKBORNE DISEASES

OF THE UNITED STATES

A Reference Manual for Healthcare Providers

Sixth Edition, 2022
CONTENTS

TICK ID . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

OVERVIEW OF TICKBORNE DISEASES . . . . . . . . . . . . . . . 4

BACTERIAL

Borrelioses

Lyme Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Tickborne Relapsing Fevers

Soft Tick Transmitted . . . . . . . . . . . . . . . . . . . . .  1

Hard Tick Transmitted 

(Borrelia miyamotoi) . . . . . . . . . . . . . . . . . . . . . 14

Rickettsioses

Anaplasmosis . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Ehrlichiosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Rocky Mountain Spotted Fever . . . . . . . . . . . . . . 24

Rickettsia parkeri Rickettsiosis . . . . . . . . . . . . . . 28

Tularemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

PARASITIC

Babesiosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

VIRAL

Heartland And Bourbon Virus Diseases . . . . . . . . . . 38

Colorado Tick Fever . . . . . . . . . . . . . . . . . . . . . . . . 40

Powassan Virus Disease . . . . . . . . . . . . . . . . . . . . . 42

TICKBORNE DISEASES ABROAD . . . . . . . . . . . . . . . . . . . 44 

TICK BITE PREVENTION AND TICK REMOVAL . . . . . . . . . 48 

LYME DISEASE PROPHYLAXIS AFTER TICK BITE . . . . . . . 49
TICK ID 1 

TICK ID

BLACKLEGGED TICK Ixodes scapularis

WHERE FOUND Widely distributed across the eastern United States

TRANSMITS Borrelia burgdorferi and B. mayonii (which cause Lyme disease), Anaplasma 

phagocytophilum (anaplasmosis), B. miyamotoi disease (a form of relapsing fever), 

Ehrlichia muris eauclairensis (ehrlichiosis), Babesia microti (babesiosis), and Powassan 

virus (Powassan virus disease)

COMMENTS The greatest risk of being bitten exists in the spring, summer, and fall in the 

Northeast, Upper Midwest, and mid-Atlantic. However, adult ticks may be out searching

for a host any time winter temperatures are above freezing. All life stages bite humans,

but nymphs and adult females are most commonly found on people

LONE STAR TICK Amblyomma americanum

WHERE FOUND Widely distributed in the eastern United States, but more common in 

the South

TRANSMITS Ehrlichia chaffeensis and E. ewingii (which cause human ehrlichiosis), 

Francisella tularensis (tularemia), Heartland virus (Heartland virus disease), Bourbon 

virus (Bourbon virus disease), and Southern tick-associated rash illness (STARI)

COMMENTS The greatest risk of being bitten exists in early spring through late fall

A very aggressive tick that bites humans. The adult female is distinguished by a white

dot or “lone star” on her back. The nymph and adult females most frequently bite

humans. Growing evidence suggests that alpha-gal syndrome (AGS) may be triggered

by the bite of lone star ticks; however, other tick species have not been ruled out

AMERICAN DOG TICK Dermacentor variabilis, D. similis

WHERE FOUND D. variabilis is widely distributed east of the Rocky Mountains. Newly

described D. similis is found west of the Rocky Mountains. More research is needed to

understand the role of these species in disease transmission

TRANSMITS Francisella tularensis (tularemia) and Rickettsia rickettsii (Rocky Mountain 

spotted fever).

COMMENTS The greatest risk of being bitten occurs during spring and summer

Adult females are most likely to bite humans

BROWN DOG TICK Rhipicephalus sanguineus

WHERE FOUND Worldwide

TRANSMITS Rickettsia rickettsii (Rocky Mountain spotted fever). Primary vector

for R. rickettsii transmission in the southwestern United States and along the 

U.S.-Mexico bord

COMMENTS Dogs are the primary host for the brown dog tick in each of its life stages, 

but the tick may also bite humans or other mammals
2 TICK ID

GROUNDHOG TICK Ixodes cookei

WHERE FOUND Throughout the eastern half of the United States

TRANSMITS Powassan virus (Powassan virus disease)

COMMENTS Also called woodchuck ticks. All life stages feed on a variety of

warm-blooded animals, including groundhogs, skunks, squirrels, raccoons, foxes, weasels, 

and occasionally people and domestic animals. Photo courtesy of Steve Jacobs, PSU Entomolog

GULF COAST TICK Amblyomma maculatum

WHERE FOUND Distributed primarily in the southeastern United States, with focal 

populations in the northeastern, midwestern, and southwestern United States

TRANSMITS R. parkeri (R. parkeri rickettsiosis), a form of spotted fever

COMMENTS Larvae and nymphs feed on birds and small rodents, while adult ticks 

feed on deer and other wildlife. Adult ticks have been associated with transmission

of R. parkeri to humans

ROCKY MOUNTAIN WOOD TICK Dermacentor andersoni

WHERE FOUND Rocky Mountain states

TRANSMITS Rickettsia rickettsii (Rocky Mountain spotted fever), Colorado tick fever 

virus (Colorado tick fever), and Francisella tularensis (tularemia)

COMMENTS Adult ticks feed primarily on large mammals. Larvae and nymphs feed

on small rodents. Adult and nymphal ticks are primarily associated with pathogen

transmission to humans

SOFT TICK Ornithodoros spp

WHERE FOUND Throughout the western half of the United States, including Texas

TRANSMITS Borrelia hermsii, B. turicatae (tickborne relapsing fever [TBRF])

COMMENTS Humans typically come into contact with soft ticks in rustic cabins. The ticks

emerge at night and feed briefly while people are sleeping. Most people are unaware that

they have been bitten. In Texas, TBRF may be associated with cave exposur

O. hermsi tick, before and after feeding. Photo taken by Gary Hettrick RML, NIAI

WESTERN BLACKLEGGED TICK Ixodes pacificus

WHERE FOUND In the Pacific Coast states

TRANSMITS Anaplasma phagocytophilum (anaplasmosis), B. burgdorferi (Lyme disease), 

and very likely B. miyamotoi (Borrelia miyamotoi disease, a form of relapsing fever)

COMMENTS Larvae and nymphs often feed on lizards, birds, and rodents, and adults 

more commonly feed on deer. Although all life stages bite humans, nymphs and adult

females are more often reported on humans
TICK ID 3 

Engorged female Ixodes scapularis tick. Color may var

TICKS THAT COMMONLY BITE HUMANS

NOTE: Relative sizes of several ticks at different life stages
4 SELECTED TICKBORNE DISEASES

OVERVIEW OF 

TICKBORNE DISEASES

SELECTED TICKBORNE DISEASES REPORTED TO CDC, U.S., 20

ANAPLASMOSIS BABESIOSIS

NOTE: Each dot represents one case. Cases are reported from the infected person’s county of

residence (where known), not necessarily the place where they were infected. Maps do not

include data if county of residence was not reported

NOTE: In 2018, no cases of tickborne illness were reported from Hawaii. In 2018, Alaska reported

8 confirmed travel-related cases of Lyme disease

NOTE: During 2018, babesiosis was reportable in Alabama, Arizona, Arkansas, California, 

Connecticut, Delaware, District of Columbia, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, 

Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, 

Montana, Nebraska, New Hampshire, New Jersey, New York, North Dakota, Ohio, Oregon, 

Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Vermont, Virginia, 

Washington, West Virginia, Wisconsin, and Wyoming
SELECTED TICKBORNE DISEASES 5 

EHRLICHIOSIS

SPOTTED FEVER RICKETTSIOSIS 

(INCLUDING ROCKY MOUNTAIN SPOTTED FEVER)

LYME DISEASE

TULAREMIA

NOTE: Anaplasmosis and ehrlichiosis were not reportable in Colorado, Idaho, New Mexico, Alaska, 

and Hawaii in 2018

NOTE: Spotted fever rickettsiosis was not reportable in Alaska and Hawaii in 2018

FOR INFORMATION ABOUT REPORTING TICKBORNE DISEASE CASES OR 

QUESTIONS ABOUT TESTING, CONTACT YOUR STATE OR LOCAL HEALTH DEPARTMENT
6 LYME DISEASE

LYME DISEASE

AGENT: Borrelia burgdorferi, B. mayonii

WHERE FOUND

Lyme disease is most frequently reported from the upper midwestern, 

northeastern, and mid-Atlantic states where it is spread by Ixodes 

scapularis ticks. Some cases are also reported from northern

California, Oregon, and Washington, where it is spread by Ixodes 

pacificus ticks. High-incidence states include Connecticut, Delaware,

Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New 

Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, 

Washington D.C., West Virginia, and Wisconsin. While these stat

account for the majority of cases, the geographic area of risk is 

expanding to include neighboring states

Dermatologic Manifestations

§ Multiple EM rashes, distant from site of tick bite

Neurologic Manifestations

§ Cranial neuritis, most commonly Bell’s palsy 

(facial paralysis, can be bilateral)

§ Lymphocytic meningitis

§ Painful radiculoneuritis involving one or 

multiple dermatomes

§ Painful peripheral motor and sensory neuropathy 

(mononeuritis multiplex)

§ Intracranial hypertension (rare)

Cardiac Manifestations

§ Lyme carditis resulting in conduction 

abnormalities (e.g., atrioventricular nod

block; myopericarditis)

§ Rarely, can be fatal

Rheumatologic Manifestations

§ Oligoarticular arthritis: transient, migratory 

arthritis and effusion in one or multiple joints, 

often large joints; may cause Baker’s cyst

§ Migratory pain in tendons, bursae, muscle, 

and bones

INCUBATION PERIOD

3–30 days

SIGNS AND SYMPTOMS

EARLY LOCALIZED (3 to 30 days after a tick bite)

§ Erythema migrans (EM)—Red annular or 

homogeneous rash at the site of tick bite; 

expands gradually over several days to >5 cm in 

diameter; central clearing may develop as the 

rash expands, resulting in a “target” or “bull’s-eye” 

appearance; may feel warm to the touch but 

rarely itchy or painful. EM occurs in 70–80% of

infected persons. The classic rash is not present

in all cases; see examples on the following pages

§ Fever, chills, malaise, fatigue, headache, 

myalgia, arthralgia

§ Lymphadenopathy 

DISSEMINATED (days to months after a tick bite)

Untreated or unnoticed early Lyme disease will 

progress to disseminated disease for about 60% 

of patients, with diverse clinical manifestations

Most manifestations will appear in the first few 

weeks to months of infection, though rheumatologic 

manifestations may be particularly delayed
LYME DISEASE 7 

GENERAL LABORATORY FINDINGS 

§ Elevated erythrocyte sedimentation rate

§ Mildly elevated hepatic transaminases

§ Microscopic hematuria or proteinuria

LABORATORY DIAGNOSIS 

1. For patients who present with an EM rash afte

being in an area where Lyme disease is common, 

Lyme disease should be diagnosed clinically 

(without diagnostic testing), as serologic tests 

may be negative during the first few weeks of 

infection before antibodies have developed

2. Serologic tests are highly sensitive in patient

with disseminated Lyme disease, and diagnosis 

relies on signs and symptoms supported by 

results of testing

3. Two-step serologic testing is recommended usin

validated first- and second-tier tests according 

to a standard or modified two-test algorithm

IgM Western immunoblot results should only be 

considered if signs and symptoms have been 

present for less than 30 days

LYME DISEASE OR STARI?

An erythema migrans-like rash has also been described in humans following bites of the lone star 

tick. This condition has been named Southern Tick-Associated Rash Illness (STARI). Although the ras

may be accompanied by systemic symptoms, disseminated or severe disease has not been reported

Because the cause of STARI is unknown, diagnostic blood tests are not available. It is not known whether

antibiotic treatment is necessary or beneficial for patients with STARI. Nevertheless, because STARI

resembles early Lyme disease, physicians often treat patients with the same antibiotics recommended 

for Lyme disease

Lone star ticks can be found from central Texas and Oklahoma eastward across the southern states and 

along the Atlantic Coast as far north as Maine

NOTES ON SEROLOGIC TESTS FOR LYME DISEASE 

§ For details, refer to the APHL guide for 

interpretation of serologic test results 

https://www.aphl.org/aboutAPH

publications/Documents/ID-2021-

Lyme-Disease-Serologic-TestingReporting.pd

§ While not necessary, acute and convalescent 

serologies may be useful for diagnosis in some 

cases, such as for patients with suspected 

re-infection

§ Serologic tests cannot be used to measure 

treatment response

§ Other conditions, including some tickborne 

infections and autoimmune diseases, can 

result in false positive test results

NOTE: Coinfection with Babesia microti or Anaplasma phagocytophilum should be considered in 

patients who present with initial symptoms that are more severe than are commonly observed 

with Lyme disease alone, especially in those who have high-grade fever for more than 48 hours 

despite appropriate antibiotic therapy or who have unexplained leukopenia, thrombocytopenia, 

or anemia. Coinfection should also be considered in patients whose erythema migrans skin

lesion has resolved but who have persistent systemic symptoms
8 LYME DISEASE

TREATMENT OF ERYTHEMA MIGRANS RASH

People treated with appropriate antibiotics in the early stages of Lyme disease usually recover rapidly 

and completely. Early diagnosis and proper antibiotic treatment of Lyme disease can help prevent

late Lyme disease. Treatment regimens listed in the following table are for the erythema migrans rash,

the most common manifestation of early Lyme disease. These regimens may need to be adjusted

depending on a person’s age, medical history, underlying health conditions, pregnancy status, 

or allergies. Consult an infectious disease specialist regarding individual patient treatment

decisions. For treating other manifestations, see www.cdc.gov/Lyme/treatme

AGE 

CATEGORY DRUG DOSAGE MAXIMUM DURATION (DAYS)*

Adults

Doxycycline

OR

100 mg, twice per day 

orally N/A 10–14

Amoxicillin

OR

500 mg, three times per 

day orally N/A 14

Cefuroxime 500 mg, twice per day 

orally N/A 14

Children

Doxycycline

OR

4.4 mg/kg per day orally,

divided into 2 doses

100 mg per 

dose 10–14

Amoxicillin

OR

50 mg/kg per day orally, 

divided into 3 doses

500 mg per 

dose 14

Cefuroxime 30 mg/kg per day orally, 

divided into 2 doses

500 mg per 

dose 14

* When different durations of antibiotics are shown to be effective for the treatment of Lyme disease, 

the shorter duration is preferred to minimize adverse effects, including infectious diarrhea and 

antimicrobial resistance

NOTE: For people intolerant of amoxicillin, doxycycline, and cefuroxime, the macrolide azithromycin 

may be used, although it is less effective. People treated with azithromycin should be closely

monitored to ensure that symptoms resolve
LYME DISEASE 9 

REFERENCES

Association of Public Health Laboratories. Suggested Reporting Language, Interpretation and Guidance

Regarding Lyme Disease Serologic Test Results. 2021. Silver Spring, MD: Association of Public Healt

Laboratories; 2021

Centers for Disease Control and Prevention. Updated CDC Recommendation for Serologic Diagnosis of

Lyme Disease. MMWR Morb Mortal Wkly Rep. 2019;68(32):70

Centers for Disease Control and Prevention. Recommendations for test performance and interpretation

from the second national conference on serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly

Rep. 1995;44:590–591

Halperin JJ, Baker P, Wormser GP. Common misconceptions about Lyme disease. Am J Med

2013;126(3):264

Hu LT. Lyme Disease. Ann Intern Med. 2016;165(9):6

Kugeler KJ, Schwartz AM, Delorey MJ, Mead PS, Hinckley AF. Estimating the Frequency of Lyme Disease

Diagnoses, United States, 2010-2018. Emerg Infect Dis. 2021;27(2):616-61

Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical Practice Guidelines by the Infectious

Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of 

Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease

Clin Infect Dis. 2021;72(1):e1-e48

Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, treatment, and prevention of Lyme disease, human

granulocytic anaplasmosis, and babesiosis: A review. JAMA. 2016;315(16):1767-7

Stanek G, Wormser GP, Gray J, et al. Lyme borreliosis. Lancet. 2012;379(9814):461-

Steere AC. Lyme Disease (Lyme Borreliosis) Due to Borrelia burgdorferi. In: Bennett J, Dolin R, Blaser M.

editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 9th ed. Elsevie

Health Sciences; 2020
10 LYME DISEASE

CLASSIC EM—CIRCULAR RED RASH WITH CENTRAL 

CLEARING THAT SLOWLY EXPANDS

Photo courtesy of Taryn Holman

BLUISH HUE WITHOUT CENTRAL CLEARING

Photo courtesy of Yevgeniy Balagula

EXPANDING LESION WITH CENTRAL CRUST ON CHEST

Photo courtesy of Bernard Cohen

EARLY, EXPANDING ERYTHEMA MIGRANS WITH NODULE

Reprinted from Bhate C, Schwartz RA. Lyme disease: Part I. Advances an

perspective. J Am Acad Dermatol. 2011;64:619-36, with permission from Elsevie

LYME DISEASE

ERYTHEMA MIGRANS RASHES

The erythema migrans (EM) rash occurs in 70-80% of patients with Lyme disease. EM rashes may have

the classic appearance or may take alternate forms; solid lesions, blue-purple hues, and crusted or 

blistering lesions have all been documented
LYME DISEASE 11 

RED, EXPANDING OVAL-SHAPED PLAQUE ON TRUNK

Photo courtesy of Alison Young

PURPLE LESION ON BACK OF KNEE

Photo courtesy of New York State Department of Health

FAINT EM ON BACK OF KNEE 

Photo courtesy of Gary Wormser, New York Medical College

EARLY DISSEMINATED LYME DISEASE—MULTIPLE LESIONS 

WITH DUSKY CENTERS ON TRUNK

Photo courtesy of Bernard Cohen

TICK BITE WITH MILD ALLERGIC REACTION

Not erythema migrans. Hypersensitivity reactions typically 

appear within the first 48 hours of tick attachment, are often 

itchy and are usually <5 cm in diameter. Localized tick bite

reactions can occur following bites from any tick species

Special thanks to DermAtlas for providing many photographs
12 TICKBORNE RELAPSING FEVER

TICKBORNE 

RELAPSING FEVER (TBRF)

(SOFT TICK RELAPSING FEVER)

AGENT: Borrelia hermsii, B. turicatae 

WHERE FOUND

In the United States, TBRF usually occurs in mountainous areas of Western 

states, where it is associated with exposure to soft ticks in rustic cabins 

(B. hermsii), and in Texas, where it is most often associated with exposure 

to soft ticks in caves (B. turicatae). 

INCUBATION PERIOD

Approximately 7 days (range 4–21), with 

recurrent febrile episodes that last around 

3 days and are separated by afebrile periods 

of approximately 7 days

SIGNS AND SYMPTOMS

TBRF most commonly presents with fever, 

headache, and myalgias. As with other

borrelioses, neurologic involvement is possible, 

including meningoencephalitis, cranial neuritis 

and ocular manifestations. Acute respiratory

distress syndrome is a rare complication

§ High fever with relapses 

§ Chills/rigors

§ Sweats

§ Headache

§ Myalgia/arthralgia

§ Dizziness

§ Nausea/vomiting

§ Facial palsy (rarely)

GENERAL LABORATORY FINDINGS 

§ Leukocytosis

§ Thrombocytopenia

§ Mild hyperbilirubinemia

§ Elevated erythrocyte sedimentation rate

§ Slightly prolonged prothrombin time (PT) and 

partial thromboplastin time (PTT)

LABORATORY DIAGNOSIS 

Tests may include the following:

§ Visualization of spirochetes by microscopy 

of peripheral blood obtained during a febrile 

episode prior to treatment

§ Molecular testing, such as PCR. Molecular tests

should be performed as early as possible, 

ideally prior to treatment or soon after. PCR

testing is more sensitive than microscopy

§ Serologic testing by immunofluorescence 

assay (IFA), enzyme immunoassay (EIA), or 

immunoblot

NOTE: TBRF can be transmitted transplacentally and has been associated with pregnancy 

complications including spontaneous abortion, premature birth, and neonatal death

NOTE: Serologic tests and some commercially available PCR tests cross-react with other Borrelia

species, including B. burgdorferi, the cause of Lyme disease
TICKBORNE RELAPSING FEVER 13 

TREATMENT

Treatment data for patients with TBRF are limited. Consider the following regimens for nonpregnant

patients who do not have neurologic complications. In pregnant individuals or when neurologic

involvement is present, initial parenteral therapy with a beta-lactam is advised; treatment should be 

continued for 10–14 days with close monitoring given the potential for severe complications

AGE 

CATEGORY DRUG DOSAGE DURATION (DAYS)

Adults

Doxycycline, oral or intravenous 

(first-line) 100 mg every 12 hours 10

Azithromycin, oral 500 mg daily 10

Penicillin G, intravenous 4,000,000 units every 6 hours 10

Ceftriaxone, intravenous 2 g daily 10

Children 

Doxycycline, oral or intravenous 

(first-line)

2.2 mg/kg per dose, every 12 hours,

maximum 100 mg/dose 10

Azithromycin, oral 10 mg/kg daily, maximum 500 mg/day 10

Penicillin G, intravenous 50,000–100,000 units/kg every 6 hours, 

maximum 4,000,000 units/dose 10

Ceftriaxone, intravenous 50–75 mg/kg daily, maximum 2 g/day 10

NOTE: When initiating antibiotic therapy, all patients should be observed during the first 4 hours of 

treatment for a Jarisch-Herxheimer reaction

See http://www.cdc.gov/relapsing-fever/clinicians. for detailed treatment informat

REFERENCES

Centers for Disease Control and Prevention. Acute respiratory distress syndrome in persons with

tickborne relapsing fever—Three states, 2004–2005. MMWR Morb Mortal Wkly Rep. 2007;56(41):

1073–1076

Centers for Disease Control and Prevention. Tickborne relapsing fever—United States, 1990–201

MMWR Morb Mortal Wkly Rep. 2015;64(3):58-60

Dworkin MS, Anderson DE Jr, Schwan TG, et al. Tick-borne relapsing fever in the northwestern

United States and southwestern Canada. Clin Infect Dis. 1998;26(1):122-3

Hashavya S, Gross I, Gross M, et al. Tickborne Relapsing Fever, Jerusalem, Israel, 2004-201

Emerg Infect Dis. 2020;26(10):2420-2423

Lyme Disease and Other Nonsyphilitic Spirochetal Infections. In: Jameson J, Fauci AS, Kasper DL,

Hauser SL, Longo DL, Loscalzo J. eds. Harrison’s Manual of Medicine, 20e. McGraw Hill; 2

Yagupsky P, Moses S. Neonatal Borrelia species infection (relapsing fever). Am J Dis Child. 198

Jan;139(1):74-6
14 HARD TICK RELAPSING FEVER

HARD TICK RELAPSING FEVER

AGENT: Borrelia miyamotoi 

WHERE FOUND

Occurs in the upper midwestern, northeastern, and mid-Atlantic states, where it 

is transmitted by Ixodes scapularis ticks, and in Pacific coastal states, where it 

is transmitted by I. pacificus ticks. Unlike Lyme disease, which most commonly

occurs in June and July, hard tick relapsing fever occurs most commonly in July 

and August

INCUBATION PERIOD

3 days to 6 weeks, exact range unknown 

SIGNS AND SYMPTOMS

Infection with B. miyamotoi most frequently presents as a self-resolving acute febrile illness, 

but the spectrum of illness varies from subclinical to severe. Severe manifestations

(e.g., meningoencephalitis) appear to be more common in people with immunocompromisin

conditions. Symptoms may include

§ Fever

§ Chills

§ Relapsing fever (10-40% of cases)

§ Fatigue

§ Arthralgia/myalgia

GENERAL LABORATORY FINDINGS 

§ Leukopenia

§ Thrombocytopenia

§ Elevated hepatic transaminases

§ Proteinuria

LABORATORY DIAGNOSIS 

§ Diagnosis relies on signs and symptoms coupled with: 

1. Polymerase chain reaction (PCR) assays that detect B. miyamotoi DNA in blood o

cerebrospinal fluid; or 

2. Serologic assa

Notably, serologic tests are most often negative during the acute presentation and are therefore 

of limited utility in diagnosis, though paired acute and convalescent tests can confirm a recent 

infection. Some serologic and PCR tests can cross-react with other Borrelia species, making

travel and tick exposure history important to distinguish between these entities
HARD TICK RELAPSING FEVER 15 

TREATMENT

There are no randomized controlled trials that evaluate treatment regimens, but in published case series, 

patients were successfully treated with antimicrobial regimens effective for Lyme disease. A 2-week

course of doxycycline or amoxicillin is appropriate for outpatient treatment of most patients, including 

young children. For persons with severe illness requiring hospitalization (e.g., meningoencephalitis

IV antibiotics such as ceftriaxone are appropriate initial therapy. When treating patients with

immunocompromising conditions for suspected B. miyamotoi infection, consultation with an infectious 

disease specialist is advised

B. miyamotoi symptoms typically improve within 24–72 hours following administration of appropriate 

antibiotics. The Jarisch-Herxheimer reaction has been described in a minority of treated patient

REFERENCES

Boden K, Lobenstein S, Hermann B, Margos G, Fingerle V. Borrelia miyamotoi–Associated

Neuroborreliosis in Immunocompromised Person. Emerg Infect Dis. 2016;22(9):1617-162

Chowdri HR, Gugliotta JL, Berardi VP, et al. Borrelia miyamotoi infection presenting as human granulocytic

anaplasmosis: a case report. Ann Intern Med. 2013;159(1):21-

Gugliotta JL, Goethert HK, Berardi VP, Telford SR 3rd. Meningoencephalitis from Borrelia miyamotoi in an

immunocompromised patient. N Engl J Med. 2013 Jan 17;368(3):240-

Jiang B, Jia N, Jiang J, Zheng Y, Chu Y, Jiang R, et al. Borrelia miyamotoi Infections in Humans and Ticks,

Northeastern China. Emerg Infect Dis. 2018;24(2):236-24

Jobe DA, Lovrich SD, Oldenburg DG, et al. Borrelia miyamotoi infection in patients from Upper

Midwestern United States, 2014-2015. Emerg Infect Dis. 2016;22(8):1471-

Krause PJ, Schwab J, Narasimhan S, et al. Hard tick relapsing fever caused by Borrelia miyamotoi in a

child. Pediatr Infect Dis J. 2016;35(12):1352-135

Krause PJ, Carroll M, Fedorova N, Brancato J, Dumouchel C, Akosa F, Narasimhan S, Fikrig E, Lane RS

Human Borrelia miyamotoi infection in California: Serodiagnosis is complicated by multiple endemic 

Borrelia species. PLoS One. 2018;13(2):e019172

Molloy PJ, Telford SR 3rd, Chowdri HR, et al. Borrelia miyamotoi disease in the northeastern United

States: a case series. Ann Intern Med. 2015;163(2):91-

Wroblewski D, Gebhardt L, Prusinski MA, et al. Detection of Borrelia miyamotoi and other tick-borne

pathogens in human clinical specimens and Ixodes scapularis ticks in New York State, 2012-2015. Ticks

Tick Borne Dis. 2017;8(3):407-411
16 ANAPLASMOSIS

ANAPLASMOSIS

AGENT: Anaplasma phagocytophilum

Anaplasmosis was formerly known as Human Granulocytic Ehrlichiosis (HGE)

Severe and life-threatening illness is less common with anaplasmosis compared 

to other rickettsial diseases, such as Rocky Mountain spotted fever (RMSF) or 

E. chaffeensis ehrlichiosis. While the case-fatality rate among patients who seek

care for the illness is <1%, predictors of a more severe course include advanced 

age, immunosuppression, comorbid medical conditions, and delay in diagnosis 

and treatment

WHERE FOUND

Anaplasmosis is most frequently reported from the Upper Midwest and northeastern United States 

in areas that correspond with the known geographic distribution of Lyme disease and other Ixodes 

scapularis-transmitted diseases. Due to the common vector, co-infection with A. phagocytophilum an

B. burgdorferi, Babesia microti, or Powassan virus is possible; illness may be marked by a more 

severe course or incomplete response to treatment

A. phagocytophilum is typically transmitted by the bite of an infected tick but may also be associated 

with blood product transfusions or organ transplant

INCUBATION PERIOD

5–14 days

SIGNS AND SYMPTOMS

§ Fever, chills, rigors 

§ Severe headache

§ Malaise

§ Myalgia

§ Gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia)

§ Rash (<10%)

The Signs and Symptoms list presents symptoms commonly seen with anaplasmosis. However, it is important to 

note that few people will develop all symptoms and the number and combination of symptoms varies greatly from 

person to person.
ANAPLASMOSIS 17 

GENERAL LABORATORY FINDINGS 

Typically observed during the first week of clinical disease:

§ Mild anemia

§ Thrombocytopenia

§ Leukopenia (characterized by relative and absolute lymphopenia and a left shift) 

§ Mild to moderate elevations in hepatic transaminases

Visualization of morulae in the cytoplasm of granulocytes during examination of blood smears is highly 

suggestive of a diagnosis; however, blood smear examination is insensitive and should never be relied 

upon solely to rule anaplasmosis in or out

LABORATORY DIAGNOSIS 

§ Detection of DNA by PCR of whole blood. This method is most sensitive during the first week of illness;

sensitivity may decrease after administration of tetracycline-class antibiotics

§ Demonstration of a four-fold rise in IgG-specific antibody titer by indirect immunofluorescence 

antibody (IFA) assay in paired serum samples. The first sample should be taken within the first

2 weeks of illness and the second should be taken 2 to 4 weeks later

§ Immunohistochemical (IHC) staining of organism from skin, tissue, or bone marrow biopsies

NOTE: Antibody titers are frequently negative in the first 7–10 days of illness. Acute antibody results

cannot independently be relied upon for confirmation

NOTE: IgM antibodies are less specific than IgG antibodies and are more likely to generate false 

positives. IgM results alone should not be used for laboratory diagnosi

CONFIRMATION OF THE DIAGNOSIS IS BASED ON LABORATORY TESTING, BUT ANTIBIOTIC 

THERAPY SHOULD NOT BE DELAYED IN A PATIENT WITH A SUGGESTIVE CLINICAL PRESENTATION
18 ANAPLASMOSIS

TREATMENT 

Anaplasmosis, ehrlichiosis, and spotted fever group rickettsioses are treated with doxycycline

Clinical suspicion of any of these diseases is sufficient to begin treatment. Delay in treatment may 

result in severe illness and even death. The regimens listed below are guidelines only and may need 

to be adjusted depending on a patient’s age, medical history, underlying health conditions, pregnancy 

status, or allergies. Consult an infectious disease specialist in cases of pregnancy or life-threatening

allergy to doxycycline

AGE 

CATEGORY DRUG DOSAGE MAXIMUM DURATION (DAYS)

Adults Doxycycline

100 mg twice 

per day, orally 

or IV

100 mg/dose Patients with suspected 

anaplasmosis infection 

should be treated with 

doxycycline for 10–14 days 

to provide appropriate 

length of therapy for 

possible co-infection 

with Lyme disease

Children 

weighing 

<100 lbs

(45.4 kg

Doxycycline

2.2 mg/kg

per dose twice 

per day, orally 

or IV

100 mg/dose 

NOTE: Use doxycycline as first-line treatment for suspected anaplasmosis in patients of all ages

The use of doxycycline to treat suspected anaplasmosis in children is recommended by both 

the CDC and the American Academy of Pediatrics Committee on Infectious Diseases. Use of

antibiotics other than doxycycline increases the risk of patient death. At the recommended dose

and duration needed to treat anaplasmosis, no evidence has been shown to cause staining of 

permanent teeth, even when multiple courses are given before the age of eight
ANAPLASMOSIS 19 

REFERENCES

Bakken, Johan S., and Dumler JS. Human granulocytic anaplasmosis. Infect Dis Clin North

2015:341–355

Centers for Disease Control and Prevention. Diagnosis and management of tickborne rickettsial

diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and 

anaplasmosis—United States: a practical guide for health care and public health professionals. MMW

2016;65 (No.RR-2

Engel J, Bradley K, et al. Revision of the national surveillance case definition for ehrlichiosis (ehrlichiosis

anaplasmosis). Council of State and Territorial Epidemiologists, Infectious Diseases Committee, 2007

Position Statement. http://c.ymcdn.com/sites/www.cste.org/resource/resmgr/PS/07-ID-

Gelfand JA, Vannier E. Ehrlichia chaffeensis (human monocytotropic ehrlichiosis), Anaplasma

phagocytophilum (human granulocytotropic anaplasmosis) and other ehrlichiae. In: Mandell GL, Bennett

JE, Dolin R, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 6th

ed. Philadelphia, PA: Churchill Livingstone; 2005. p. 2310–2

Mowla SJ, Drexler NA, et al. Ehrlichiosis and anaplasmosis among transfusion and transplant recipients

in the United States. Emerg Infect Dis. 2021;27(11):2768-277

Todd SR, Dahlgren FS, et al. No visible dental staining in children treated with doxycycline for suspected

Rocky Mountain spotted fever. J Pediatr 2015;166(5):1246-5

Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment and prevention of Lyme

disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious 

Diseases Society of America. Clin Infect Dis 2006; 43:1089–113
20 EHRLICHIOSIS

EHRLICHIOSIS

AGENTS: Ehrlichia chaffeensis, Ehrlichia ewingii, Ehrlichia muris eauclairensis

E. chaffeensis can cause fatal illness, whereas no deaths have been reported for 

E. ewingii or E. muris euclairensis ehrlichiosis

Incidence of E. chaffeensis enhrlichiosis generally increases with age, however, 

case-fatality rates are highest among children aged <10 years and adults 

aged ≥70 years

WHERE FOUND

Ehrlichiosis is most frequently reported from the southeastern and south-central United States, from the 

East Coast extending westward to Texas. The areas from which most cases are reported correspond with

the known geographic distribution of the lone star tick (Amblyomma americanum), which is associated 

with transmission of both E. chaffeensis and E. ewingii. In 2019, four states (Missouri, Arkansas, North

Carolina, and New York) accounted for nearly half of all reported cases of E. chaffeensis ehrlichiosis

Since 2009, >115 cases of ehrlichiosis caused by E. muris eauclairensis have been identified in 

patients in the Upper Midwest. The tick responsible for transmitting this new subspecies of Ehrlichia is

Ixodes scapularis, and the clinical presentation is generally similar to those associated with infections 

caused by E. chaffeensis and E. ewingii.

INCUBATION PERIOD

5–14 days

SIGNS AND SYMPTOMS

§ Fever, chills

§ Headache 

§ Malaise 

§ Muscle pain 

§ Gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia) 

§ Altered mental status 

§ Rash (more commonly reported among children)

The Signs and Symptoms list presents symptoms commonly seen with ehrlichiosis. However, it is 

important to note that few people will develop all symptoms, and the number and combination of 

symptoms varies greatly from person to person.
EHRLICHIOSIS 21 

GENERAL LABORATORY FINDINGS 

Typically observed during the first week of clinical disease:

§ Thrombocytopenia

§ Leukopenia (absolute)

§ Anemia (generally occurs later in illness than thrombocytopenia or leukopenia)

§ Mild to moderate elevations in hepatic transaminases 

During the acute stage of illness, morulae can be detected in about 20% of patients. E. chaffeensis most

commonly infects monocytes, whereas E. ewingii more commonly infects granulocytes. The target cell of

E. muris eauclairensis has not yet been identified. Visualization of morulae during examination of blood

smears is highly suggestive of a diagnosis; however, blood smear examination is insensitive and should 

never be relied upon solely to rule ehrlichiosis in or out

LABORATORY DIAGNOSIS

§ Detection of DNA by PCR of whole blood. This method is most sensitive during the first week of

illness and sensitivity can decrease after administration of tetracycline-class antibiotics

§ Demonstration of a four-fold rise in IgG-specific antibody titer by indirect immunofluorescence 

antibody (IFA) assay in paired serum samples. The first sample should be taken within the first

2 weeks of illness, and the second should be taken 2 to 4 weeks later

§ Immunohistochemical (IHC) staining of organism from skin, tissue, or bone marrow biopsies

NOTE: Antibody titers are frequently negative in the first 7–10 days of illness. Acute antibody results

cannot independently be relied upon for confirmation

NOTE: IgM antibodies are less specific than IgG antibodies and are more likely to generate false 

positives. IgM results alone should not be used for laboratory diagnosi

CONFIRMATION OF THE DIAGNOSIS IS BASED ON LABORATORY TESTING, BUT ANTIBIOTIC 

THERAPY SHOULD NOT BE DELAYED IN A PATIENT WITH A SUGGESTIVE CLINICAL PRESENTATION
22 EHRLICHIOSIS

TREATMENT

Anaplasmosis, ehrlichiosis, and spotted fever group rickettsioses are treated with doxycycline. Clinical

suspicion of any of these diseases is sufficient to begin treatment. Delay in treatment may result in

severe illness and death. The regimens listed below are guidelines only and may need to be adjusted 

depending on a patient’s age, medical history, underlying health conditions, pregnancy status, or 

allergies. Consult an infectious disease specialist in cases of pregnancy or life-threatening allergy

to doxycycline

AGE 

CATEGORY DRUG DOSAGE MAXIMUM DURATION (DAYS)

Adults Doxycycline

100 mg twice 

per day, orally 

or IV

100 mg/dose Patients should be treated 

for at least 3 days after the 

fever subsides and until 

there is evidence of clinical 

improvement. Minimum

course of treatment is 

5–7 days

Children 

weighing 

<100 lbs

(45.4 kg

Doxycycline

2.2 mg/kg

per dose twice 

per day, orally 

or IV

100 mg/dose

NOTE: Use doxycycline as first-line treatment for suspected ehrlichiosis in patients of all ages. The use

of doxycycline to treat suspected ehrlichiosis in children is recommended by both the CDC and 

the American Academy of Pediatrics Committee on Infectious Diseases. Use of antibiotics other

than doxycycline increases the risk of patient death. At the recommended dose and duration

needed to treat ehrlichiosis, no evidence has been shown to cause staining of permanent teeth, 

even when multiple courses are given before the age of eight
EHRLICHIOSIS 23 

REFERENCES

Centers for Disease Control and Prevention. Diagnosis and management of tickborne rickettsial

diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and 

anaplasmosis—United States: a practical guide for health care and public health professionals. MMW

2016; 65 (No.RR-2

Dumler JS, Madigan JE, Pusterla N, et al. Ehrlichioses in humans: epidemiology, clinical presentation,

diagnosis, and treatment. Clin Infect Dis 2007 Jul 15;45 Suppl 1:S45–5

Engel J, Bradley K, et al. Revision of the national surveillance case definition for ehrlichiosis. Council o

State and Territorial Epidemiologists, Infectious Diseases Committee, 2007 Position Statement

http://c.ymcdn.com/sites/www.cste.org/resource/resmgr/PS/07-ID-0

Gelfand JA, Vannier E. Ehrlichia chaffeensis (human monocytotropic ehrlichiosis), Anaplasma

phagocytophilum (human granulocytotropic anaplasmosis) and other ehrlichiae. In: Mandell GL, Bennett

JE, Dolin R, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases

6th ed. Philadelphia, PA: Churchill Livingstone; 2005. p. 2310–2

Harris, RM, Couturier BA, Sample SC. Expanded Geographic Distribution and Clinical Characteristics of

Ehrlichia ewingii Infections, United States. Emerg Infect Dis 2016 May;22(5):862-86

Johnson DK, Schiffman EK, Davis JP, et al. Human infection with Ehrlichia muris-like pathogen, United

States, 2007-2013(1). Emerg Infect Dis 2015 Oct;21(10):1794-179

Mowla SJ, Drexler NA, Cherry CC, et al. Ehrlichiosis and anaplasmosis among transfusion and transplant

recipients in the United States. Emerg Infect Dis. 2021 Nov;27(11):2768-277

Pritt BS, Sloan LM, Johnson DK, et al. Emergence of a new pathogenic Ehrlichia species, Wisconsin and

Minnesota, 2009. N Engl J Med 2011; 365:422-42

Saha A, Browning C, Dandamudi R, et al. Donor-derived ehrlichiosis: 2 clusters following solid organ

transplantation. Clin Infect Dis. 2022 Mar 9;74(5):918-92

Todd SR, Dahlgren FS, et al. No visible dental staining in children treated with doxycycline for suspected

Rocky Mountain spotted fever. J Pediatr 2015 May;166(5):1246-125
24 ROCKY MOUNTAIN SPOTTED FEVER

ROCKY MOUNTAIN 

SPOTTED FEVER (RMSF)

AGENT: Rickettsia rickettsii

RMSF is most often transmitted by the American dog tick in the Eastern, 

Central, and Western United States; by the Rocky Mountain wood tick in 

the Rocky Mountain states; and by the brown dog tick in the Southwestern 

United States, along the U.S.-Mexico border. RMSF can be rapidly fatal if n

treated within the first 5 days of symptoms. Before tetracycline antibiotics were

available, case fatality rates ranged from 20–80%

WHERE FOUND

Since 2010, cases of RMSF are reported as spotted fever rickettsiosis along with other spotted fevers 

like Rickettsia parkeri rickettsiosis in national surveillance. RMSF has become increasingly common

in certain areas of Arizona over the last several years; between 2002–2021 more than 500 cases and 

28 fatalities occurred

INCUBATION PERIOD

3–12 days

SIGNS AND SYMPTOMS

EARLY (1–4 DAYS)

§ High fever

§ Severe headache 

§ Malaise

§ Myalgia

§ Edema around eyes and on the back of hands

§ Gastrointestinal symptoms (nausea, 

vomiting, anorexia)

LATE (5 DAYS AND BEYOND)

§ Altered mental status, coma, cerebral edema

§ Respiratory compromise (pulmonary edema, 

ARDS)

§ Necrosis, requiring amputation

§ Multiorgan system damage (CNS, renal failure)

RASH

§ Typically appears 2–5 days after onset of 

symptoms; approximately 10% of RMSF 

patients never develop a rash

§ Decision to treat should not be based on 

presence of rash

Early Rash

§ Maculopapular: Small, flat, pink, non-itchy 

spots (macules) initially appear on the wrists, 

forearms, and ankles then spread to the trunk 

and sometimes palms and soles

Late Rash

§ Petechial: Red to purple spots (petechiae) are 

usually not seen until day 6 or later after onset 

of symptoms

§ Petechial rash is considered a sign of 

progression to severe disease. Every attempt

should be made to begin treatment before 

petechiae develop
ROCKY MOUNTAIN SPOTTED FEVER 25 

GENERAL LABORATORY FINDINGS 

§ Thrombocytopenia

§ Elevated hepatic transaminases

§ Hyponatremia 

NOTE: Laboratory values are often within normal limits in early illness

LABORATORY DIAGNOSIS

§ Demonstration of a four-fold rise in IgG-specific antibody titer by indirect immunofluorescence 

antibody (IFA) assay in paired serum samples. The first sample should be taken within the first

2 weeks of illness and the second should be taken 2 to 4 weeks later

§ Detection of DNA in a skin biopsy specimen of a rash lesion by PCR assay or in an acute phase whole 

blood specimen. Additionally, new pan-Rickettsia and R. rickettsii-specific PCR assays are available at

some local and state health departments

§ Immunohistochemical (IHC) staining of organism from skin or tissue biopsy specimen

NOTE: Antibody titers are frequently negative in the first 7–10 days of illness. Acute antibody results

cannot be independently relied upon for confirmation

NOTE: IgM antibodies are less specific than IgG antibodies and are more likely to generate false 

positives. IgM results alone should not be used for laboratory diagnosi

Confirmation of the diagnosis is based on laboratory testing, but antibiotic therapy should not be 

delayed in a patient with a suggestive clinical presentation. Antibiotics are more likely to prevent

fatal outcome from RMSF if started within the first 5 days of symptoms
26 ROCKY MOUNTAIN SPOTTED FEVER

TREATMENT

Anaplasmosis, ehrlichiosis, and spotted fever group rickettsioses are treated with doxycycline. Clinical

suspicion of any of these diseases is sufficient to begin treatment. Delay in treatment may result in

severe illness and even death. The regimens listed below are guidelines only and may need to be 

adjusted depending on a patient’s age, medical history, underlying health conditions, pregnancy 

status, or allergies. Consult an infectious disease specialist in cases of pregnancy or life-threatening

allergy to doxycycline

AGE 

CATEGORY DRUG DOSAGE MAXIMUM DURATION (DAYS)

Adults Doxycycline

100 mg twice 

per day, orally 

or IV

100 mg/dose Patients should be treated 

for at least 3 days after the 

fever subsides and until 

there is evidence of clinical 

improvement. Minimum

course of treatment is 

5–7 days

Children 

weighing 

<100 lbs

(45.4 kg

Doxycycline

2.2 mg/kg

per dose twice 

per day, orally 

or IV

100 mg/dose

NOTE: Use doxycycline as the first-line treatment for suspected RMSF in patients of all ages. The use

of doxycycline to treat suspected RMSF in children is recommended by both the CDC and the 

American Academy of Pediatrics Committee on Infectious Diseases. Use of antibiotics other than

doxycycline increases the risk of patient death. At the recommended dose and duration needed

to treat RMSF, no evidence has been shown to cause staining of permanent teeth, even when 

multiple courses are given before the age of eight
ROCKY MOUNTAIN SPOTTED FEVER 27 

REFERENCES

Centers for Disease Control and Prevention. Diagnosis and management of tickborne rickettsial

diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and 

anaplasmosis—United States: a practical guide for health care and public health professionals. MMW

2016;65 (No.RR-2

Demma LJ, Traeger MS, Nicholson WL, et al. Rocky Mountain spotted fever from an unexpected tick vector

in Arizona. N Engl J Med 2005;353:587–9

Elghetany MT, Walker DH. Hemostatic changes in Rocky Mountain spotted fever and Mediterranean

spotted fever. Am J Clin Pathol 1999;112:159–6

Holman RC, Paddock CD, Curns AT, et al. Analysis of risk factors for fatal Rocky Mountain spotted fever:

evidence for superiority of tetracyclines for therapy. J Infect Dis 2001;184:1437–4

Jay R, Armstrong PA. Clinical characteristics of Rocky Mountain spotted fever in the United States:

A literature review. J Vector Borne Dis. 2020 Apr-Jun;57(2):114-12

Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic delay and mortality in cases of Rocky Mountain

spotted fever. Clin Infect Dis 1995;20:1118–2

Massey EW, Thames T, Coffey CE, et al. Neurologic complications of Rocky Mountain spotted feve

South Med J 1985;78:1288–90, 1303

McQuiston JH, Wiedeman C, Singleton J, et al. Inadequacy of IgM antibody tests for diagnosis of Rocky

Mountain Spotted Fever. Am J Trop Med Hyg. 2014 Oct;91(4):767-7

Paddock CD, Alvarez-Herandez G. Rickettsia rickettsii (Rocky Mountain spotted fever). In: Principles an

Practice of Pediatric Infectious Diseases. 5th ed. Philadelphia, PA: Elsevier; 2017. p. 952-

Regan JJ, Traeger MS, Humpherys D, et al. Risk factors for fatal outcome from Rocky Mountain spotted

fever in a highly endemic area—Arizona, 2002–2011. Clin Infect Dis 2015;60:1659–6

Smithee L, et al. Public health reporting and national notification for spotted fever rickettsiosis (including

Rocky Mountain spotted fever). Council of State and Territorial Epidemiologists, Infectious Diseases

Committee, 2009 Position Statement

http://c.ymcdn.com/sites/www.cste.org/resource/resmgr/PS/09-ID-1

Todd SR, Dahlgren FS, et al. No visible dental staining in children treated with doxycycline for suspected

Rocky Mountain spotted fever. J Pediatr 2015;166(5):1246-5

Traeger MS, Regan JJ, Humpherys D, et al. Rocky Mountain spotted fever characterization and comparison

to similar illnesses in a highly endemic area—Arizona, 2002–2011. Clin Infect Dis 2015;60:1650–
28 R. PARKERI RICKETTSIOSI

RICKETTSIA PARKERI

RICKETTSIOSIS

AGENT: Rickettsia parkeri 

R. parkeri is closely related to R. rickettsii, the causative agent of Rocky Mountain 

spotted fever (RMSF). R. parkeri rickettsiosis and RMSF have similar signs

and symptoms, including fever, headache, and rash, but also typically include 

the appearance of an inoculation eschar (seen at right) at the site of tick 

attachment. Eschar is not common in cases of RMS

WHERE FOUND

R. parkeri rickettsiosis is transmitted by Gulf Coast ticks found primarily in the southeastern United 

States, with focal populations in the northeastern, midwestern, and southeastern United States

INCUBATION PERIOD

2–10 days

SIGNS AND SYMPTOMS

R. parkeri rickettsiosis is characteristically less severe than RMSF and almost always associated with 

an inoculation eschar (ulcerated, necrotic lesion) at the site of tick attachment

Several days after an eschar appears, the following can develop:

§ Fever

§ Headache

§ Rash (sparse maculopapular or papulovesicular eruptions on the trunk and extremities)

§ Muscle aches

NOTE: R. parkeri rickettsiosis can be difficult to distinguish from RMSF and other spotted fevers, 

especially during early stages of these diseases. Eschars are uncommonly identified in persons

with RMSF

GENERAL LABORATORY FINDINGS 

§ Mildly elevated hepatic transaminases

§ Mild leukopenia

§ Mild thrombocytopenia, less common
R. PARKERI RICKETTSIOSIS 29

LABORATORY DIAGNOSIS 

§ Detection of rickettsial DNA by PCR in eschar swab, whole blood, or skin biopsy

§ Demonstration of a four-fold rise in IgG-specific antibody titer by indirect immunofluorescence 

antibody (IFA) assay in paired serum samples. The first sample should be taken within the first

2 weeks of illness and the second should be taken 2 to 4 weeks later

NOTE: Species-level testing for R. parkeri is not commercially available. RMSF antibody tests are

available commercially and often cross-react

NOTE: IgM antibodies are less specific than IgG antibodies and are more likely to generate false 

positives. IgM results alone should not be used for laboratory diagnosi

NOTE: Acute antibody results cannot independently be relied upon for confirmation

TREATMENT

See Rocky Mountain spotted fever treatment on page 26

REFERENCES

Centers for Disease Control and Prevention. Diagnosis and management of tickborne rickettsial

diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and 

anaplasmosis—United States: a practical guide for health care and public health professionals. MMW

2016;65 (No.RR-2

Paddock CD, Finley RW, Wright CS, et al. Rickettsia parkeri rickettsiosis and its clinical distinction from

Rocky Mountain spotted fever. Clin Infect Dis 2008;47:1188-9

Paddock CD, Goddard J. The evolving medical and veterinary importance of the Gulf Coast tick (Acari:

Ixodidae). J Med Entomol 2015;52:230–52. http://dx.doi.org/10.1093/jme/t

Straily A, Feldpausch A, Ulbrich C, et al. Notes from the Field: Rickettsia parkeri rickettsiosis—Georgia,

2012–2014. MMWR Morb Mortal Wkly Rep 2016;65:718-71

Herrick KL, Pena SA, Yaglom HD, et al. Rickettsia parkeri rickettsiosis, Arizona, USA. Emerg Infect D

2016;22:780-785

CONFIRMATION OF THE DIAGNOSIS IS BASED ON LABORATORY TESTING, BUT ANTIBIOTIC 

THERAPY SHOULD NOT BE DELAYED IN A PATIENT WITH A SUGGESTIVE CLINICAL PRESENTATION
30 TULAREMIA

TULAREMIA

AGENT: Francisella tularensis

WHERE FOUND

Tularemia has been reported in all states except Hawaii, but it is most 

common in the south-central United States, the Great Plains region, and parts 

of Massachusetts

INCUBATION PERIOD

3–5 days (range 1–21 days)

SIGNS AND SYMPTOMS

The clinical presentation of tularemia depends on many factors, including the route of inoculation and 

subtype of F. tularensis. Tularemia can be serious or fatal without adequate treatment. Unusual and

severe clinical manifestations have been described in patients with immunocompromising conditions

§ Fever, chills

§ Headache

§ Malaise, fatigue

§ Anorexia

§ Myalgia

§ Chest discomfort, cough

§ Sore throat

§ Vomiting, diarrhea

§ Abdominal pain

(ULCERO) GLANDULAR

§ Localized lymphadenopathy

§ Cutaneous ulcer at infection 

site (not always present)

OCULOGLANDULAR 

§ Photophobia

§ Vision impairment/loss 

§ Conjunctivitis

§ Regional lymphadenopathy

OROPHARYNGEAL

§ Severe throat pain

§ Exudative pharyngitis or 

tonsillitis

§ Regional lymphadenopathy

PNEUMONIC 

§ Non-productive cough

§ Substernal tightness

§ Pleuritic chest pain

§ Hilar adenopathy, infiltrate, 

or pleural effusion may be 

present on chest X-ray

TYPHOIDAL 

§ Characterized by any 

combination of the general 

symptoms without the 

localizing symptoms of 

other syndromes

§ May have infiltrates in chest 

radiograph in the absence of 

respiratory symptoms 

Tularemia is caused by the highly infectious F. tularensis bacteria. It is spread through exposure to

infected arthropods (including deer flies and several species of ticks), contact with infected carcasses 

or animals (such as rabbits, hares, and rodents), contaminated food or water, or inhalation of aerosols 

(such as by mowing over an infected rabbit carcass)
TULAREMIA 31 

GENERAL LABORATORY FINDINGS 

§ Hyponatremia

§ Leukocytosis

§ Thrombocytopenia

§ Elevated hepatic transaminases

§ Elevated creatine kinase

§ Elevated erythrocyte sedimentation rate

§ Myoglobinuria 

§ Sterile pyuria 

LABORATORY DIAGNOSIS

Isolation of F. tularensis in culture is optimal for diagnosis but can be challenging due to the slowgrowing, fastidious nature of the organism. Appropriate specimens for culture include swabs or scrapings

of ulcers, lymph node aspirates or biopsies, pharyngeal swabs, or respiratory specimens (e.g., pleura

fluid), depending on the form of illness. Blood cultures are often negativ

Seroconversion from negative to positive IgM and/or IgG can also confirm the diagnosis when tularemia 

is suspected. Ideally, these are performed as paired acute and convalescent specimens, the latter

collected 2–3 weeks after initial illness

When available, other tests can be useful, including:

§ Direct immunofluorescence assay (DFA)

§ Immunohistochemical staining

§ PCR assay

Clinicians who suspect tularemia should alert the laboratory to the possible need for special safety 

procedures to minimize risk of laboratory transmission
32 TULAREMIA

TREATMENT

These regimens may need to be adjusted depending on a person’s age, medical history, underlying 

health conditions, pregnancy status, or allergies. Consult an infectious disease specialist regarding

individual patient treatment decisions

AGE 

CATEGORY DRUG DOSAGE MAXIMUM DURATION (DAYS)

Adults

Gentamicin*

5 mg/kg IM or IV daily (with 

desired peak serum levels of 

at least 5 mcg/mL)

Monitor serum drug levels Minimum 10

Ciprofloxacin* 400 mg IV or 500 mg PO 

twice daily N/A 10–14

Doxycycline 100 mg IV or PO twice daily N/A 14–21

Children

Gentamicin* 2.5 mg/kg IM or IV 3 times

daily**

Monitor serum drug levels 

and consult a pediatric 

infectious disease specialist

Minimum 10

Ciprofloxacin* 15 mg/kg IV or PO twice daily 800 mg per day 10

Doxycycline 2.2mg/kg IV or PO twice daily 100mg IV or PO twice daily 14–2

* Not a U.S. FDA-approved use but has been used successfully to treat patients with tularem

** Once-daily dosing could be considered in consultation with a pediatric infectious disease specialist 

and a pharmacist

NOTE: Gentamicin is preferred for treatment of severe tularemia. Dose should be adjusted for

renal insufficiency

NOTE: For tularemic meningitis, combination therapy should be considered in consultation with 

an infectious disease specialist

See www.cdc.gov/tularemia/clinicians/ for detailed treatment informati

Tularemia prophylaxis is recommended in cases of laboratory exposure to infectious materials

§ Doxycycline (100 mg orally twice daily for 14 days) is generally recommended for prophylaxis 

in adults

§ Ciprofloxacin (500 mg orally twice daily) is not FDA-approved for prophylaxis of tularemia but 

has demonstrated efficacy in various studies and may be an alternative for patients unable to 

take doxycycline
TULAREMIA 33 

REFERENCES

Auwaerter PG, Penn RL. Francisella tularensis (Tularemia). In: Bennett J, Dolin R, Blaser M., edit

Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 9th ed. Elsevier Health

Sciences; 2020

Centers for Disease Control and Prevention. Tularemia—United States, 2001-2010. MMWR Morb Morta

Wkly Rep. 2013;62(47):963–966

Dennis D, Inglesby TV, Henderson DA, et al. Tularemia as a biological weapon: medical and public health

management. JAMA. 2001;285(21):2763–277

Feldman KA, Enscore RE, Lathrop SL, et al. An outbreak of primary pneumonic tularemia on Martha’s

Vineyard. NEJM. 2001;345:1601–160

Johansson A, Berglund L, Sjöstedt A, et al. Ciprofloxacin for treatment of tularemia. Clin Infect Dis

2001;33:267–8

Tarnvik A. WHO Guidelines on tularaemia. Vol. WHO/CDS/EPR/2007.7. Geneva: World He

Organization, 2007
34 BABESIOSIS

BABESIOSIS

AGENT: Babesia microti and other Babesia species

Babesiosis is a disease caused by parasites that infect red blood cells

Most U.S. cases are caused by B. microti, which is transmitted mainly by Ixode

scapularis ticks, primarily in the Northeast and Upper Midwest and sporadically 

on the West Coast. Babesia parasites can also be transmitted via blood

transfusion, perinatally, and via organ transplantation, anywhere, at any time 

of year. In 2019, the FDA licensed tests for the detection of Babesia species to

utilize for screening of donors and recommended year-round regional testing for 

blood donations in areas endemic for babesiosis. Babesia infection can range from

asymptomatic to life-threatening. Risk factors for severe babesiosis include 

splenia, advanced age (age >50), and impaired immune function

WHERE FOUND

Babesiosis is most frequently reported from the Northeastern and Upper Midwestern United States in 

areas where B. microti is endemic; cases peak during spring and summer months. Sporadic cases of

infection caused by novel Babesia agents have been detected in other U.S. regions, including the Wes

Coast. Cases of babesiosis linked to B. divergens-like organisms have occurred in the Midwest region,

Arkansas, Kentucky, Pennsylvania and Washington State. Cases linked to B. duncani have occurred on

the West Coast of the United States. Transfusion-associated cases of babesiosis can occur anywhere in

the country, at any time of year

INCUBATION PERIOD

1–4 weeks following tick bite; 1–9 weeks after contaminated blood transfusion (up to 24 weeks)

SIGNS AND SYMPTOMS

Not all infected persons are symptomatic or febrile (an estimated 25% of infected adults and 50% of children are 

asymptomatic). The clinical manifestations, if any, usually develop within several weeks after exposure, but may 

develop or recur months later (for example, in the context of surgical splenectomy).

§ Fever, chills, sweats

§ Malaise, fatigue

§ Myalgia, arthralgia, headache

§ Gastrointestinal symptoms, such as anorexia and nausea (less common: abdominal pain, vomiting)

§ Dark urine

§ Less common: dry cough, sore throat, photophobia, conjunctival injection

§ Mild splenomegaly, mild hepatomegaly, or jaundice may occur in some patients

§ Severe cases can be associated with marked thrombocytopenia, disseminated intravascular 

coagulation, hemodynamic instability, acute respiratory distress, renal failure, hepatic compromise, 

altered mental status, and death
BABESIOSIS 35 

GENERAL LABORATORY FINDINGS 

Findings consistent with hemolysis include:

§ Hemolytic anemia with decreased haptoglobin, elevated lactate dehydrogenase (LDH) values, 

and reticulocytosis

§ Thrombocytopenia

§ Elevated creatinine and blood urea nitrogen (BUN) values

§ Mildly elevated hepatic transaminase values

§ Proteinuria

LABORATORY DIAGNOSIS 

§ Identification of intraerythrocytic Babesia parasites by light-microscopic examination of a 

peripheral blood smear; or

§ Positive Babesia (or B. microti) polymerase chain reaction (PCR) analysis; or

§ Demonstration of a Babesia-specific antibody titer by indirect fluorescent antibody (IFA) testing for 

total immunoglobulin (Ig) or IgG 

NOTE: If the diagnosis of babesiosis is being considered, manual (nonautomated) review of blood 

smears should be requested explicitly. In symptomatic patients with acute infection, Babesi

parasites typically can be detected by blood-smear examination by experienced technicians, 

although multiple smears may need to be examined. It can be difficult to distinguish between

Babesia and malaria parasites and even between parasites and artifacts (such as stain 

or platelet debris). Consider having a reference laboratory confirm the diagnosis, and if

applicable, perform serologic or molecular testing to get a species-level identification

NOTE: Antibody detection by serologic testing can provide supportive evidence for the diagnosis but 

does not reliably distinguish between active and prior infection
36 BABESIOSIS

TREATMENT

Treatment decisions and regimens should consider the patient’s age, clinical status, immunocompetence, 

splenic function, comorbidities, pregnancy status, other medications, and allergies. Expert consultation

is recommended for persons who have or are at risk for severe or relapsing infection or who are at either 

extreme of age (e.g., >50 years of age or neonate

The typical regimens for adults are provided in the table below. Note that some patients diagnosed

with babesiosis may have concurrent Lyme disease, or anaplasmosis or may be infected with other 

pathogens transmitted by Ixodes scapularis in a region. For pediatric dosing and non-B. microti

treatment recommendations please reference the Clinical Practice Guidelines by the Infectious Diseases 

Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis. 

AGE 

CATEGORY DRUG PATIENT CATEGORY DOSAGE DURATION (DAYS)*

Adults***

(Preferred 

Regimen)

Azithromycin 

+

Atovaquone (with a 

fatty meal)

Prescribe together

Non-hospitalized 

(mild to moderate 

disease)

Azithromycin 500 mg orally on day 1; on 

subsequent days, give 250 mg every 24 hours 7–10

Atovaquone 750 mg orally every 12 hours

Hospitalized 

(acute severe 

disease)

Azithromycin 500 mg IV every 24 hours until 

symptoms lessen, then transition to all oral 

step-down therapy 7–10

Atovaquone 750 mg orally every 12 hours

Hospitalized 

(step-down 

therapy)

Azithromycin 250-500 mg** orally every 

24 hours 7–10

Atovaquone 750 mg orally every 12 hours

(Alternative 

Regimen)****

Clindamycin 

+ 

Quinine

Prescribe together

Non-hospitalized 

(mild to moderate 

disease)

Clindamycin 600 mg orally every 8 hours 

7–10

Quinine 650 mg orally every 8 hours

Hospitalized 

(acute severe 

disease)

Clindamycin 600 mg IV every 6 hours until 

symptoms lessen, then transition to oral 

step-down therapy 7–10

Quinine 650 mg orally every 8 hours

Hospitalized 

(step-down 

therapy)

Clindamycin 600 mg orally every 8 hours

7–10

Quinine 650 mg orally every 8 hours

* The duration of therapy may be greater than 10 days for patients that are immunocompromised; highly 

immunocompromised patients may benefit from 6+ weeks

** In immunocompromised adults, consider azithromycin doses of 500-1000 mg daily

*** Patients with high-grade parasitemia (>10%), severe hemolytic anemia, or severe pulmonary, renal, 

or hepatic compromise may benefit from exchange transfusion. Expert consultation is strongly advise

****Patients who fail to improve while on therapy with the preferred regimen or who are unable to take 

the preferred regimen should be treated with clindamycin and quinine.
BABESIOSIS 37 

NOTE: Most persons without clinical manifestations of infection do not require treatment unless 

parasites are seen on thin blood smear for >30 days

REFERENCES

Centers for Disease Control and Prevention. Babesiosis surveillance—18 states, 2011. MM

2012;61: 505–9

Diuk-Wasser MA, Vannier E, Krause PJ. Coinfection by Ixodes tick-borne pathogens: Ecological,

epidemiological, and clinical consequences. Trends Parasitol. 2016;32(1):30-4

Herwaldt BL, Linden JV, Bosserman E, et al. Transfusion-associated babesiosis in the United States:

a description of cases. Ann Intern Med. 2011;115:509–1

Glanternik JR, Baine IL, Rychalsky MR, et al. A cluster of cases of Babesia microti among neonates

traced to a single unit of donor blood. Pediatr Infect Dis J. 2018 Mar;37(3):269-27

Krause PJ, Auwaerter PG, Bannuru RR, et al. Clinical practice guidelines by the Infectious Diseases

Society of America (IDSA): 2020 guideline on diagnosis and management of babesiosis. Clin Infect Dis

2021 Jan 27;72(2):e49-e64

Krause PJ. Human babesiosis. Int J Parasitol. 2019 Feb;49(2):165-1

Kumar A, O’Bryan J, Krause PJ. The global emergence of human babesiosis. Pathogen

2021;10(11):1447

Kumar P, Marshall B, deBlois G, et al. A cluster of transfusion-associated babesiosis in extremely low

birthweight premature infants. J Perinatol. 2012;32, 731–73

Moniuszko A, Dunaj J, Swi ̨ecicka I, et al. Co-infections with Borrelia species, Anaplasma

phagocytophilum and Babesia spp. in patients with tick-borne encephalitis. Eur J Clin Microbio

Infect Dis. 2014 Oct;33(10):1835-41

Steiner FE, Pinger RR, Vann CN, et al. Infection and co-infection rates of Anaplasma phagocytophilu

variants, Babesia spp., Borrelia burgdorferi, and the rickettsial endosymbiont in Ixodes scapulari

(Acari: Ixodidae) from sites in Indiana, Maine, Pennsylvania, and Wisconsin. J Med Entomol. 2008

Mar;45(2):289-97

US Food and Drug Administration. Guidance for industry: recommendations for reducing the risk of

transfusion-transmitted babesiosis. Silver Spring, MD: CBER: Office of Communication OCOD; 201

Vannier E, Krause PJ. Human babesiosis. N Engl J Med. 2012;366:2397–4

Vannier EG, Diuk-Wasser MA, Ben Mamoun C, et al. Babesiosis. Infect Dis Clin North A

015;29(2):357-370

Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of

Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the 

Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089–134. Erratum in: Clin Infect Di

2007;45:941

Wormser GP, Prasad A, Neuhaus E, et al. Emergence of resistance to azithromycin-atovaquone in

immunocompromised patients with Babesia microti infection. Clin Infect Dis. 2010;50:381–
38 HEARTLAND AND BOURBON VIRUS DISEASES

HEARTLAND VIRUS DISEASE

AGENT: Heartland virus

WHERE FOUND

As of 2017, more than 50 cases of Heartland virus disease have been reported 

from states in the Midwest and the South

INCUBATION PERIOD

Specific ranges are unknown; most patients report a tick bite in the 2 weeks 

prior to illness

SIGNS AND SYMPTOMS

§ Fever

§ Fatigue

§ Decreased appetite

§ Headache

§ Arthralgia

§ Myalgia

§ Nausea

§ Diarrhea

GENERAL LABORATORY FINDINGS 

§ Leukopenia

§ Thrombocytopenia

§ Mild to moderate elevation of hepatic transaminases

BOURBON VIRUS DISEASE

As of 2017, a limited number of Bourbon virus disease cases have been identified in the Midwest 

and southern United States. Some people who have been infected later died. Scientists continue t

investigate possible symptoms caused by this new virus. Symptoms of people diagnosed with Bourbon

virus disease included fever, tiredness, rash, headache, body aches, nausea, and vomiting. General

laboratory findings included leukopenia and thrombocytopenia
HEARTLAND VIRUS AND BOURBON VIRUS DISEASES 39 

LABORATORY DIAGNOSIS 

Molecular and serologic testing for Heartland virus infection can be performed at CDC. There are no

commercially available tests for Heartland virus infection in the United States. Please contact your state

health department if you have a patient with an acute illness that may be compatible with Heartland 

virus disease

TREATMENT

Treatment of Heartland virus disease is supportive. Many patients diagnosed with the disease have

required hospitalization. With supportive care, most people have fully recovered; however, a few older

individuals with medical comorbidities have died

REFERENCES

Basile AJ, Horiuchi K, Goodman CH, et al. Development of diagnostic microsphere-based immunoassays

for Heartland virus. J Clin Virol. 2021;134:10469

Brault AC, Savage HM, Duggal NK et al. Heartland Virus Epidemiology, Vector Association, and Disease

Potential. Viruses. 2018 Sep 14;10(9):49

McMullan LK, Folk SM, Kelly AJ, et al. A new phlebovirus associated with severe febrile illness in Missour

N Eng J Med 2012;367:834-41

Muehlenbachs A, Fata CR, Lambert AJ, et al. Heartland virus associated death in Tennessee. Clin Infec

Dis 2014;59(6):845-850

Godsey MS, Savage HM, Burkhalter KL, et al. Transmission of Heartland virus (Bunyaviridae:

Plebovirus) by experimentally infected Amblyomma americanum (Acari: Ixodidae). J Med Entomo

2016;53(5):1226-1233

Savage HM, Godsey MS, Panella NA, et al. Surveillance for Heartland virus (Bunyaviridae: Phlebovirus)

in Missouri during 2014: First detection of virus in adults of Amblyomma americanum (Acari: Ioxodidae)

J Med Entomol 2016;53(3):607-612

Staples JE, Pastula DM, Panella AJ, et al. Investigation of Heartland virus disease throughout the

United States, 2013-2017. Open Forum Infect Dis. 2020 Apr 11;7(5):ofaa12
40 COLORADO TICK FEVER 

COLORADO TICK FEVER (CTF)

AGENT: Colorado tick fever virus

WHERE FOUND

The geographic range of Colorado tick fever virus includes the Western United 

States, primarily Colorado, Utah, Montana, and Wyoming. Although rare, the virus

can also be transmitted from person-to-person via blood transfusion

INCUBATION PERIOD

1–14 days

SIGNS AND SYMPTOMS

§ Fever, chills, headache, myalgias, and lethargy

§ ~50% of patients have a biphasic illness with symptoms remitting after 2 to 4 days, but then 

recurring 1 to 3 days later

§ Conjunctival injection, pharyngeal erythema and lymphadenopathy may be present

§ Maculopapular or petechial rash in <20% of patients

§ Prolonged convalescence characterized by weakness and fatigue is common in adults

§ Life-threatening complications and death are rare and usually associated with disseminated 

intravascular coagulation or meningoencephalitis in children

GENERAL LABORATORY FINDINGS 

§ Leukopenia 

§ Moderate thrombocytopenia

LABORATORY DIAGNOSIS 

Preliminary diagnosis of Colorado tick fever (CTF) is based on signs and symptoms, places and 

dates of travel, activities, and history of potential tick exposure. Acute samples should be tested by

reverse-transcriptase polymerase chain reaction (RT-PCR) to detect viral RNA as antibody production 

is delayed until 14–21 days after onset of symptoms

NOTE: CSF, cerebrospinal fluid; CNS, central nervous system
COLORADO TICK FEVER 41 

TIMING OF SPECIMEN 

COLLECTION SPECIMENS PREFERRED TEST

<14 days after symptom onset Serum (CSF if suspected CNS involvement) RT-PCR for viral RNA

≥14 days after symptom onset Serum (CSF if suspected CNS involvement)

Antibody testing*; 

consider RT-PCR 

for samples from 

days 14–21

*If possible, acute and convalescent samples, collected at least 2 weeks apart, with the convalescent 

sample collected at least 3 weeks after symptom onset, should be obtained to look for seroconversion or 

a 4-fold rise in antibody titers typically using a plaque reduction neutralization test (PRNT)

NOTE: CTF testing is available at some commercial and state health department laboratories and 

at CDC. Contact your state or local health department for assistance with diagnostic testin

CTF cases are reportable to local public health authorities in certain states

REFERENCES

Brackney MM, Marfin AA, Staples JE, et al. Epidemiology of Colorado tick fever in Montana, Utah, and

Wyoming, 1995–2003. Vector Borne Zoonotic Dis 2010;10:381–38

Centers for Disease Control and Prevention. West Nile virus and other nationally notifiable arboviral

diseases—United States, 2016. MMWR 2018; 67(1);13-1

Kadkhoda K, Semus M, Jelic T, Walkty A. Case report: a case of Colorado tick fever acquired in

southwestern Saskatchewan. Am J Trop Med Hyg. 2018;98:891–89

McDonald E, George D, Rekant S, et al. Notes from the field: Investigation of Colorado tick fever virus

disease cases—Oregon, 2018. Morb Mortal Wkly Rep. 2019;68:289–29

Staples JE, Fischer M. Coltiviruses (Colorado Tick Fever). In: Principles and Practice of Pediatri

Infectious Diseases, 5th edition. Eds: Long SS, Prober CG, Fischer M. Elsevier 2018:1119–11

Goodpasture HC, Poland JD, Francy DB, et al. Colorado tick fever: clinical, epidemiologic, and laboratory

aspects of 228 cases in Colorado in 1973–1974. Ann Intern Med 1978;88:303–31

Lambert AJ, Kosoy O, Velez JO, et al. Detection of Colorado Tick Fever viral RNA in acute human serum

samples by a quantitative real-time RT-PCR assay. J Virol Methods 2007;140:43–4

Romero JR, Simonsen KA. Powassan encephalitis and Colorado tick fever. Infect Dis Clin North 

2008;22:545–559

Williamson BN, Fischer RJ, Lopez JE, et al. Prevalence and strains of Colorado tick fever virus in Rocky

Mountain wood ticks in the Bitterroot Valley, Montana. Vector Borne Zoonotic Dis. 2019;19:694–70

Yendell SJ, Fischer M, Staples JE. Colorado tick fever in the United States, 2002-2012. Vector Born

Zoonotic Dis 2015;15:311–316
42 POWASSAN VIRUS DISEASE

POWASSAN VIRUS DISEASE

AGENT: Powassan virus 

WHERE FOUND

Most cases have occurred primarily in northeastern states and the Great Lakes region. Less frequently,

cases have been identified in Mid-Atlantic States

INCUBATION PERIOD

1–4 weeks

SIGNS AND SYMPTOMS

§ Fever, headache, vomiting, and generalized weakness

§ Usually progresses to meningoencephalitis. May include meningeal signs, altered mental status,

seizures, aphasia, paresis, movement disorders, or cranial nerve palsies

GENERAL LABORATORY FINDINGS 

§ CSF findings include lymphocytic pleocytosis (neutrophils can predominate early), normal or mildly 

elevated protein, and normal glucose

LABORATORY DIAGNOSIS 

§ Primarily through testing available at CDC and selected state health departments; limited 

commercial testing

§ Measurement of virus-specific IgM antibodies in serum or CSF. Cross-reaction with other flaviviruses

(e.g., West Nile, dengue, or St. Louis encephalitis viruses) can occur; plaque reduction neutralizati

tests should be performed to confirm the diagnosis

§ RT-PCR may detect viral RNA in acute CSF specimens or tissues, but this method should not be used 

to rule out the diagnosis, as antibodies are often present at the onset of neuroinvasive signs and 

symptoms. RT-PCR might be more appropriate for very acute samples or samples obtained from

patients who are immunocompromised

TREATMENT

No specific antiviral treatment for Powassan virus disease is available. Patients with suspected Powassan

virus disease should receive supportive care as appropriate
POWASSAN VIRUS DISEASE 43 

REFERENCES

Ebel GD. Update on Powassan virus: emergence of a North American tick-borne flavivirus. Annu Re

Entomol. 2010;55:95–110

El Khoury MY, Camargo JF, White, JL, et al. Potential role of deer tick virus in Powassan encephalitis

cases in Lyme disease-endemic areas of New York, USA. Emerg Infect Dis. 2013;19:1926–193

Hermance ME, Thangamani S. Powassan virus: an emerging arbovirus of public health concern in

North America. Vector Borne Zoonotic Dis. 2017;17:453–46

Hinten SR, Beckett GA, Gensheimer KF, et al. Increased recognition of Powassan encephalitis in the

United States, 1999–2005. Vector Borne Zoonotic Dis. 2008;8(6):733–74

Johnson DK, Staples JE, Sotir MJ, et al. Tickborne Powassan virus infections among Wisconsin resident

Wis Med J. 2010;109(2):91-7

Krow-Lucal ER, Lindsey NP, Fischer M, Hills SL. Powassan virus disease in the United States, 2006-201

Vector Borne Zoonotic Dis. 2018;18:286-90

Piantadosi A, Rubin DB, McQuillen DP, et al. Emerging cases of Powassan virus encephalitis in New

England: Clinical presentation, imaging, and review of the literature. Clin Infect Dis. 2016;62:707–71

Taylor L, Condon T, Destrampe EM, et al. Powassan virus infection likely acquired through blood

transfusion presenting as encephalitis in a kidney transplant recipient. Clin Infect Dis

2021;72(6):1051-54

Tutolo JW, Staples JE, Sosa L, et al. Notes from the field: Powassan virus disease in an infant

Connecticut, 2016. MMWR Morb Mortal Wkly Rep. 2017;66:408-
44 TICKBORNE DISEASES ABROAD

TICKBORNE DISEASES ABROAD

AFRICAN TICK BITE FEVER (ATBF)

AGENT: Rickettsia africae

African tick bite fever (ATBF) is the most commonly diagnosed rickettsial disease among returning 

international travelers. ATBF is transmitted by Amblyomma hebraeum and A. variegatum ticks. Travelassociated cases of ATBF often occur in clusters with exposure during activities such as safari tours

game hunting, and bush hiking

WHERE FOUND

Sub-Saharan Africa, Caribbean (French West Indies), and Oceania

INCUBATION PERIOD

Typically 5–7 days but may be as long as 10 days

SIGNS AND SYMPTOMS

ATBF is typically a mild-to-moderate disease; no known deaths are attributable to infection with R. africae

ATBF is almost always associated with an inoculation eschar (see R. parkeri rickettsiosis) at the site of tick 

attachment. Multiple eschars are described in approximately 20–50% of patients with ATBF

Several days after eschar(s) appear, the following can develop:

§ Fever

§ Headache

§ Myalgia

§ Regional lymphadenopathy 

§ Rash (generalized with maculopapular or vesicular eruptions)

GENERAL LABORATORY FINDINGS

§ Similar to other Rickettsia, see R. parkeri rickettsiosis.

LABORATORY DIAGNOSIS

Confirmation of the diagnosis is based on laboratory testing, but antibiotic treatment should not be 

delayed pending laboratory confirmation

§ ATBF can be confirmed using IFA or detection of Rickettsial DNA by PCR of eschar swab, skin biopsy, or 

whole blood. See R. parkeri rickettsiosis

§ ATBF can be confirmed by comparing acute and convalescent (taken 4–6 weeks following illness onset) 

samples for evidence of seroconversion in IgG antibodies

TREATMENT

 See RMSF treatment.
TICKBORNE DISEASES ABROAD 45 

LYME DISEASE (EUROPE AND ASIA)

AGENTS: Borrelia afzelii, B. garinii, B. burgdorferi sensu stricto,

and B. bavariensis (previously considered a variant of B. garinii)

Outside North America, Borrelia spp. that cause Lyme disease are transmitted through the bite of

infected Ixodes ricinus and I. persulcatus ticks

WHERE FOUND

In Europe, Lyme disease is endemic from southern Scandinavia into the northern Mediterranean 

countries of Italy, Spain, Portugal, and Greece and east from the British Isles into central Russia

Incidence is highest in Central and Eastern European countries. In Asia, infected ticks occur from

western Russia through Mongolia, northeastern China, and Japan; however, human infection appears to 

be uncommon in some of these areas

INCUBATION PERIOD

3–30 days

SIGNS AND SYMPTOMS

Outside of North America, most infections are caused by B. afzelii, B. garinii, B. burgdorferi sensu stricto, 

and B. bavariensis (previously considered a variant of B. garinii), with each causing somewhat different 

clinical manifestations

As in the United States, the erythema migrans (EM) rash is the most common early manifestation; later 

neurologic, cardiac, and rheumatologic disease may occur. In European Lyme disease, the EM rash may

spread more slowly and is less commonly accompanied by systemic symptoms. Atrophic skin lesions

(acrodermatitis chronica atrophicans) are a frequent late manifestation of infection with B. afzelii.

In Lyme disease caused by B. garinii, some individuals may develop Bannwarth syndrome, a severe 

neuroborreliosis characterized by radiculopathy, neuropathy, and lymphocytic meningitis

LABORATORY CONFIRMATION

Antibodies to Borrelia species that cause Lyme disease outside the United States may not be reliably 

detected by all tests used in the United States. Providers who suspect internationally-acquired Lyme

disease should use diagnostic tests that have been validated for these species

TREATMENT

See Lyme disease treatment

REFERENCES

Steere AC, Strle F, Wormser GP, et al. Lyme borreliosis. Nat Rev Dis Primers. 2016;2:160

Stone BL, Tourand Y, Brissette CA. Brave new worlds: The expanding universe of Lyme disease. Vecto

Borne Zoonotic Dis. 2017;17(9):619-629.

Vandekerckhove O, De Buck E, Van Wijngaerden E. Lyme disease in Western Europe: an emerging

problem? A systematic review. Acta Clin Belg. 2021;76(3):244-25
46 TICKBORNE DISEASES ABROAD

TICKBORNE ENCEPHALITIS (TBE)

AGENT: Tick-borne encephalitis virus

TBE is transmitted through the bite of infected Ixodes ricinus and I. persulcatus ticks

WHERE FOUND

Endemic in focal areas of Europe and Asia, extending from western and northern Europe through to 

northern and eastern Asia. The highest disease incidence has been reported from the Baltic states,

Slovenia, and Czech Republic. TBE may also be acquired by ingestion of unpasteurized dairy products

from infected goats, sheep, or cows

INCUBATION PERIOD

8 days (range, 4–28 days)

SIGNS AND SYMPTOMS

TBE disease often presents with mild illness but can cause neuroinvasive disease (i.e., asepti

meningitis, encephalitis). The course of illness can be monophasic or biphasic. If biphasic, the tw

phases are:

§ First phase: nonspecific febrile illness with headache, myalgia, and fatigue. Usually lasts for several

days and may be followed by an afebrile and relatively asymptomatic period

§ Second phase: central nervous system involvement. Findings depend on the specific presentation but

might include meningeal signs, altered mental status, cognitive dysfunction, ataxia, rigidity, seizures, 

tremors, cranial nerve palsies, and limb paresis

LABORATORY CONFIRMATION

During the first phase of the illness, TBE virus or viral RNA can sometimes be detected in serum samples 

by virus isolation or RT-PCR. However, by the time neurologic symptoms are recognized, the virus or

viral RNA is usually undetectable. Therefore, virus isolation and RT-PCR should not be used to rule out

a diagnosis of TBE. Clinicians should contact their state or local health department or CDC’s Division of

Vector-Borne Diseases (970-221-6400) for assistance with diagnostic testing

TREATMENT

There is no specific antiviral treatment for TBE; therapy consists of supportive care and management 

of complications

PREVENTION

Inactivated TBE vaccine (manufactured as TICOVAC) is licensed and available in the United States. This

vaccine is approved for use in people aged 1 years and older and is administered as a three-dose series

TBE vaccine is recommended for persons who are moving or traveling to a TBE-endemic area and will 

have extensive exposure to ticks based on their planned outdoor activities and itinerary. In addition, TBE

vaccine may be considered for persons traveling or moving to a TBE-endemic area who might engage in 

outdoor activities in areas ticks are likely to be found
TICKBORNE DISEASES ABROAD 47 

ADDITIONAL TRAVEL-ASSOCIATED TICKBORNE INFECTIONS

DISEASES AND ETIOLOGIC AGENTS GEOGRAPHIC LOCATION AND ADDITIONAL RISK FACTORS

Mediterranean spotted fever (also 

known as boutonneuse fever)

Europe (Mediterranean basin), Middle East, Indian subcontinent, 

and Africa. Caused by Rickettsia conorii, symptoms include fever,

headache, muscle pain, eschar (usually single), and rash. It is

typically a moderately severe illness, and can be fatal

Crimean-Congo hemorrhagic fever

CCHF virus

Asia, Africa, and Europe. May also be acquired by contact with

infected blood or saliva or inhalation of infected aerosols

Omsk hemorrhagic fever

Omsk hemorrhagic fever virus

Southwestern Russia. May also be acquired by direct contact with

infected muskrats

Kyasanur Forest disease

Southern India, Saudi Arabia (aka Alkhurma disease in Saudi 

Arabia). Typically associated with exposure while harvesting

forest products

REFERENCES

Centers for Disease Control and Prevention. Diagnosis and management of tickborne rickettsial

diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and 

anaplasmosis—United States: a practical guide for health care and public health professionals. MMW

2016;65 (No.RR-2

Centers for Disease Control and Prevention. Brunette GW, Kozarsky PE, Cohen NJ, et al. CDC Healt

Information for International Travel 2016 (Yellow Book). New York, NY: Oxford University Press; 2016

European Centre for Disease Prevention and Control, Tick-borne diseases 

(https://ecdc.europa.eu/en/tick-borne-disease

Fournier PE, Jensenius M, Laferl H, et al. Kinetics of antibody responses in Rickettsia africae and

Rickettsia conorii infections. Clin Diag Lab Immunol 2002;9(2):324-32

Goodman JL, Dennis DT, Sonenshine DE, editors. Tick-borne diseases of humans. Washington, DC: ASM

Press; 2005

Jensenius M, Fournier PE, Kelly P, et al. African tick bite fever. Lancet Infect Dis 2003;3(9):557-5

Parola P, Paddock CD, Socolovschi C, et al. Update on tick-borne rickettsioses around the world: a

geographic approach. Clin Microbiol Rev 2013;26(4):657-70
48 TICK BITES/PREVENTION

TICK BITES/PREVENTION

EMBEDDED TICK TICK REMOVAL, STEP 1

Photo courtesy of Mike Wren, NY State 

Department of Health

TICK REMOVAL, STEP 2

Photo courtesy of Mike Wren, NY State 

Department of Health

TICK BITE PREVENTION

1. Know where to expect ticks. Ticks live in grassy, brushy, or wooded areas, or on animals. Spending t

outside walking your dog, camping, gardening, or hunting could bring you in close contact with ticks

Many people get ticks in their own yard or neighborhood. Soft ticks that spread tickborne relapsing

fever (TBRF) most often live in caves and rodent-infested rustic cabins

2. Use Environmental Protection Agency (EPA)-registered insect repellents containing DEET, picaridin

IR3535, oil of lemon eucalyptus, para-menthane-diol, or 2-undecanone. Treat clothing and gear, such

as boots, pants, socks, and tents with products containing 0.5% permethri

3. Treat dogs for ticks as recommended by a veterinari

4. Check for ticks daily, especially under the arms, in and around the ears, inside the belly button, behin

the knees, between the legs, around the waist, and on the hairline and scalp

5. Shower soon after being outdoo

For more tips, see www.cdc.gov/lyme/pre

TICK REMOVAL

1. Use fine-tipped tweezers to grasp the tick as close to the skin’s surface as possible. The key is 

remove the tick as soon as possible. Avoid using nail polish, petroleum jelly, or heat to make the tick

detach from the skin

2. Pull upward with steady, even pressure. Don’t twist or jerk the tick; this can cause the mouth-parts 

break off and remain in the skin. If you are unable to remove the mouth parts easily, leave them alone

and let the skin heal

3. After removing the tick, thoroughly clean the bite area and your hands with rubbing alcohol, an iodin

scrub, or soap and water

48 TICK BITES/PREVENTION
LYME DISEASE PROPHYLAXIS AFTER TICK BITE 49 

LYME DISEASE PROPHYLAXIS

AFTER TICK BITE

In areas that are highly endemic for Lyme disease, a single prophylactic dose of doxycycline (200 mg for 

adults or 4.4 mg/kg for children of any age weighing less than 45 kg) may be used to reduce the risk of

acquiring Lyme disease after a high-risk tick bite

Benefits of prophylaxis may outweigh risks when all of the following circumstances are present:

1. Where the tick bite occurred, are ticks likely to be infected with Borrelia burgdorfer

2. Was the tick removed within the last 72 hours

3. Was the tick’s body engorged with bloo

(not flat)? 

4. Was the tick an Ixodes (blacklegged) tic

5. Is doxycycline safe for the patient? Considerations include allergy to doxycycline, pregnancy

and lactation

Antibiotic treatment following a tick bite is not recommended as a means to prevent anaplasmosis, 

babesiosis, ehrlichiosis, Rocky Mountain spotted fever, or other rickettsial diseases. Instead, 

persons who experience a tick bite should be alert for symptoms suggestive of tickborne illness and 

consult a physician if fever, rash, or other symptoms of concern develop

REFERENCES

Nadelman RB, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an

Ixodes scapularis tick bite. N Engl J Med. 2001;345(2):79-8

Harms MG, et al. A single dose of doxycycline after an Ixodes ricinus tick bite to prevent Lyme borreliosis:

An open-label randomized controlled trial. J Infect. 2021;82(1):98-10

FLAT

NYMPH

ENGORGED

ADULT
For more information, please contact:

Centers for Disease Control and Prevention

Division of Vector-Borne Diseases

3156 Rampart Road, Fort Collins, CO 80521

Telephone: 1-800-CDC-INFO (232-4636)

TTY: 1-888-232-63548

Contact: www.cdc.gov/cdc-inf

Web: www.cdc.gov/tic

CS332249-A

Based on “Tickborne Diseases in Massachusetts: A Physician’s Reference Manual,” 

produced by collaboration between MDPH, Nancy Shadick, MD, MPH, and 

Nancy Maher, MPH of the RBB Arthritis and Musculoskeletal Diseases Clinical 

Research Center at Brigham and Women’s Hospital and Dennis Hoak, MD, 

of Martha’s Vineyard Hospital