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## Complete Summary

#### GUIDELINE TITLE

Diagnosis and management of tickborne rickettsial diseases: Rocky
Mountain spotted fever, ehrlichioses, and anaplasmosis - United States.
A practical guide for physicians and other health-care and public health
professionals.

#### BIBLIOGRAPHIC SOURCE(S)

Chapman AS, Bakken JS, Folk SM, Paddock CD, Bloch KC, Krusell A, Sexton
DJ, Buckingham SC, Marshall GS, Storch GA, Dasch GA, McQuiston JH,
Swerdlow DL, Dumler SJ, Nicholson WL, Walker DH, Eremeeva ME, Ohl CA.
Diagnosis and management of tickborne rickettsial diseases: Rocky
Mountain spotted fever, ehrlichioses, and anaplasmosis\--United States:
a practical guide for physicians and other health-care and public health
professionals. MMWR Recomm Rep 2006 Mar 31;55(RR-4):1-27. \[104
references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16572105)

#### GUIDELINE STATUS

This is the current release of the guideline.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Tickborne rickettsial diseases (TBRD) including:

-   Rocky Mountain spotted fever (RMSF)

-   Human monocytotropic (or monocytic) ehrlichiosis (HME)

-   Human granulocytotropic (or granulocytic) anaplasmosis (HGA,
    formerly known as human granulocytotropic ehrlichiosis or HGE)

-   *Ehrlichia ewingii* infection

-   Other emerging TBRD

#### GUIDELINE CATEGORY

Diagnosis\
Management\
Prevention\
Risk Assessment

#### CLINICAL SPECIALTY

Emergency Medicine\
Family Practice\
Infectious Diseases\
Internal Medicine\
Pediatrics

#### INTENDED USERS

Advanced Practice Nurses\
Emergency Medical Technicians/Paramedics\
Health Care Providers\
Nurses\
Physician Assistants\
Physicians\
Public Health Departments

#### GUIDELINE OBJECTIVE(S)

-   To provide primary care physicians and physician extenders with
    practical information to assist with the diagnosis and care of
    patients with tickborne rickettsial diseases (TBRD)

-   To provide a framework for recognizing suggestive symptoms,
    considering likely alternative diagnoses, eliciting relevant
    history, requesting appropriate diagnostic tests, and initiating
    prompt, effective treatment

#### TARGET POPULATION

-   Individuals with probable or confirmed tickborne rickettsial
    diseases (TBRD)

-   Individuals at risk for TBRD

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Diagnosis and Management**

1.  Thorough clinical history eliciting recent tick bite or tick
    exposure, travel to endemic areas, or reports of tickborne
    rickettsial diseases (TBRD) among family members, coworkers or pets

2.  Clinical assessment and laboratory diagnostic tests (signs and
    symptoms of TBRD, complete blood count, metabolic panel, peripheral
    blood smear, cerebrospinal fluid analysis)

3.  Immediate antibiotic therapy

    -   Doxycycline (first-line)

    -   Chloramphenicol (alternative)

4.  Prophylactic use of antibiotics after a tick bite *(considered but
    not recommended)*

5.  Management of severe manifestations of TBRD

6.  Confirmatory diagnostic tests

    -   Blood smear microscopy

    -   Serologic testing (indirect immunofluorescence antibody \[IFA\]
        assay)

    -   Amplification of specific DNA by polymerase chain reaction (PCR)

    -   Immunohistochemical staining of biopsied skin or autopsy tissues

    -   Culture (rarely used for diagnosis)

7.  Surveillance and reporting of TBRD

**Prevention**

1.  Avoiding tick bites

2.  Limiting exposure to tick habitats

3.  Inspecting body for ticks

4.  Removing ticks

#### MAJOR OUTCOMES CONSIDERED

-   Epidemiology of tickborne rickettsial infection

-   Utility of clinical assessment and laboratory tests in differential
    diagnosis

-   Sensitivity and specificity of confirmatory diagnostic assays

-   Effectiveness of antibiotic therapy

-   Case fatality rate

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Not stated

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Expert Consensus (Committee)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

Not applicable

#### METHODS USED TO ANALYZE THE EVIDENCE

Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

In October 2004, to address the need for a consolidated resource for the
diagnosis and management of tickborne rickettsial diseases (TBRD), the
Center for Disease Control and Prevention\'s (CDC\'s) Viral and
Rickettsial Zoonoses Branch collaborated with 11 clinical and academic
specialists of Rocky Mountain spotted fever (RMSF), human
granulocytotropic (or granulocytic) anaplasmosis (HGA) and human
monocytotropic (or monocytic) ehrlichiosis (HME). These external
contributors were invited by CDC subject matter specialists to
participate among clinicians and researchers in the field of TBRD, based
on direct working interactions related to case consultation and
recognized expertise from peer-reviewed publications. In December 2004,
the framework of this report was developed by CDC\'s Viral and
Rickettsial Zoonoses Branch, based on a summary of the peer-reviewed
published reports on the epidemiology and clinical aspects of TBRD.
External contributors further developed recommendations for the
diagnosis and treatment of TBRD based on their clinical research and
experience. All work group collaborators reviewed and provided input and
approved the final content of this report.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

All work group collaborators reviewed and provided input and approved
the final content of this report.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

**Table: Selected features of Rocky Mountain spotted fever,**^1^ human
monocytotropic ehrlichiosis, human granulocytotropic anaplasmosis^2^,
and *Ehrlichia ewingii* infection \-- United States^3^

  ---------------------------------------------------------------------------------------------------------------------------------------------
  **Agent (disease)** **Primary        **Approximate       **Incubation     **Common     **Common laboratory  **Rash**        **Case-fatality
                      vector(s)**      distribution^4^**   period(days)**   initial      abnormalities**                      rate**
                                                                            signs and                                         
                                                                            symptoms**                                        
  ------------------- ---------------- ------------------- ---------------- ------------ -------------------- --------------- -----------------
  *Rickettsia         *Dermacentor     Widespread in the   2-14             Fever,       Thrombocytopenia,    Maculopapular   5%-10%
  rickettsii* (Rocky  variabilis*      United States,                       nausea,      mild hyponatremia,   rash            
  Mountain spotted    (American dog    especially South                     vomiting,    and mildly elevated  approximately   
  fever)              tick),           Atlantic and South                   myalgia,     hepatic transaminase 2-4 days after  
                      *Dermacentor     Central states                       anorexia,    levels               fever onset in  
                      andersoni*                                            and headache                      50%-80% of      
                      (Rocky Mountain                                                                         adults (\>90%   
                      wood tick), and                                                                         in children);   
                      *Rhipicephalus                                                                          might involve   
                      sanguineus*                                                                             palms and soles 
                      (brown dog tick)                                                                                        
                      in AZ^5^                                                                                                

  *Ehrlichia          *Amblyomma       South and           5-14             Fever,       Leukopenia,          Rash in \<30%   2%-3%
  chaffeensis* (human americanum*      Mid-Atlantic,                        headache,    thromobocytopenia,   of adults and   
  monocytotropic      (lone star tick) North/South Central                  malaise, and and elevated serum   approximately   
  ehrlichiosis)                        United States, and                   myalgia      transaminase levels  60% of children 
                                       isolated areas of                                                                      
                                       New England                                                                            

  *Anaplasma          *Ixodes          New England, North  5-21             Fever,       Leukopenia,          Rare            \<1%
  phagocytophilum*    scapularis* and  Central and Pacific                  headache,    thrombocytopenia,                    
  (human              *Ixodes          states                               malaise,     elevated serum                       
  granulocytotropic   pacificus*                                            myalgia, and transaminase levels                  
  anaplasmosis)       (blacklegged                                          vomiting                                          
                      tick) in the                                                                                            
                      United States                                                                                           

  *Ehrlichia ewingii* *Amblyomma       South Atlantic and  5-14             Fever,       Leukopenia,          Rare            No documented
  infection           americanum*      South Central                        headache,    thromobocytopenia,                   fatalities
                      (lone star tick) United States to                     myalgia,     and elevated serum                   
                                       isolated areas of                    nausea, and  transaminase levels                  
                                       New England                          vomiting                                          
  ---------------------------------------------------------------------------------------------------------------------------------------------

^1^ SOURCE: Walker DH, Raoult D. *Rickettsia rickettsii* and other
spotted fever group rickettsiae (Rocky Mountain spotted fever and other
spotted fevers). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell,
Douglas, and Bennett\'s principles and practice of infectious diseases.
6th ed. Philadelphia, PA: Churchill Livingstone; 2005:2287-95.

^2^ SOURCE: Walker DH, Dumler JS. *Ehrlichia chaffeensis* (human
monocytotropic ehrlichiosis), *Anaplasma phagocytophilum* (human
granulocytotropic anaplasmosis) and other ehrlichiae. In: Mandell GL,
Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett\'s principles
and practice of infectious diseases. 6th ed. Philadelphia, PA: Churchill
Livingstone; 2005:2310-8.

^3^ Treatment for each of these diseases is the same: adults,
doxycycline 100 mg orally (PO) or intravenously (IV) twice daily; and
children, doxycycline 2.2 mg/kg administered PO or IV twice daily.

^4^ *Mountain*: Montana, Idaho, Wyoming, Colorado, New Mexico, Arizona,
Utah, Nevada. *East South Central*: Kentucky, Tennessee, Alabama,
Mississippi. *East North Central*: Ohio, Indiana, Illinois, Michigan,
Wisconsin. *West South Central*: Arkansas, Louisiana, Oklahoma, Texas.
*West North Central*: Minnesota, Iowa, Missouri, North Dakota, South
Dakota, Nebraska, Kansas. *Pacific*: Washington, Oregon, California.
*New England*: Massachusetts, Connecticut, Rhode Island, New Hampshire.
*South Atlantic*: Delaware, Maryland, Virginia, District of Columbia,
West Virginia, North Carolina, South Carolina, Georgia, Florida.
*Mid-Atlantic*: New York, New Jersey, Pennsylvania.

^5^ SOURCE: Demma LJ, Traeger MS, Nicholson WL, et al. Rocky Mountain
spotted fever from an unexpected tick vector in Arizona. N Engl J Med
2005;353:587-94.

**Table: Case definitions for Rocky Mountain spotted fever^1^, human
monocytotropic ehrlichiosis (HME), human granulocytotropic anaplasmosis
(HGA), and unspecified ehrlichiosis**^2^

+----------+------------+-------------+--------------+--------------+
| **Rocky  |            | **E         |              |              |
| Mountain |            | hrlichiosis |              |              |
| spotted  |            | and         |              |              |
| fever**  |            | ana         |              |              |
|          |            | plasmosis** |              |              |
+==========+============+=============+==============+==============+
| **       | Tickborne  | Tickborne   |              |              |
| Clinical | illness    | illness     |              |              |
| descr    | cha        | ch          |              |              |
| iption** | racterized | aracterized |              |              |
|          | by acute   | by acute    |              |              |
|          | onset of   | onset of    |              |              |
|          | fever and  | fever,      |              |              |
|          | possible   | headache,   |              |              |
|          | headache,  | myalgia,    |              |              |
|          | malaise,   | and         |              |              |
|          | myalgia,   | possible    |              |              |
|          | and        | malaise.    |              |              |
|          | nause      | Nausea,     |              |              |
|          | a/vomiting | vomiting,   |              |              |
|          | or         | or rash     |              |              |
|          | neurologic | might be    |              |              |
|          | signs. A   | observed in |              |              |
|          | macular or | certain     |              |              |
|          | mac        | cases.      |              |              |
|          | ulopapular | Clinical    |              |              |
|          | rash is    | laboratory  |              |              |
|          | reported   | findings    |              |              |
|          | in the     | might       |              |              |
|          | majority   | include     |              |              |
|          | of         | thromb      |              |              |
|          | patients   | ocytopenia, |              |              |
|          | and is     | leukopenia, |              |              |
|          | frequently | and         |              |              |
|          | observed   | possibly    |              |              |
|          | on the     | elevated    |              |              |
|          | palms and  | liver       |              |              |
|          | soles.     | enzymes.    |              |              |
|          |            | Intra       |              |              |
|          |            | cytoplasmic |              |              |
|          |            | morulae     |              |              |
|          |            | might be    |              |              |
|          |            | visible in  |              |              |
|          |            | the         |              |              |
|          |            | leukocytes  |              |              |
|          |            | of certain  |              |              |
|          |            | patients.   |              |              |
+----------+------------+-------------+--------------+--------------+
| ** **    |            | **HME**     | **HGA**      | *            |
|          |            |             |              | *Unspecified |
|          |            |             |              | eh           |
|          |            |             |              | rlichiosis** |
+----------+------------+-------------+--------------+--------------+
| **La     | Serologic  | De          | D            | D            |
| boratory | evidence   | monstration | emonstration | emonstration |
| cr       | of 4-fold  | of 4-fold   | of 4-fold    | of 4-fold    |
| iteria** | change in  | change in   | change in    | change in    |
|          | serum      | antibody    | antibody     | antibody     |
|          | antibody   | titer to    | titer to     | titer to     |
|          | titer      | *Ehrlichia  | *Anaplasma   | more than    |
|          | against    | c           | phag         | one          |
|          | *          | haffeensis* | ocytophilum* | *Ehrlichia*  |
|          | Rickettsia | antigen by  | antigen by   | species in   |
|          | r          | IFA in      | IFA in       | which a      |
|          | ickettsii* | paired      | paired serum | dominant     |
|          | antigens   | serum       | samples;     | reactivity   |
|          | between    | samples;    |              | cannot be    |
|          | paired     |             | *or*         | established; |
|          | serum      | *or*        |              |              |
|          | samples,   |             | positive PCR | *or*         |
|          | as         | positive    | assay and    |              |
|          | determined | PCR^6^      | confirmation | Id           |
|          | by IFA^3^  | assay and   | of *A.       | entification |
|          | or         | c           | phag         | of a species |
|          | ELISA^4^;  | onfirmation | ocytophilum* | other than   |
|          |            | of *E.      | DNA;         | *E.          |
|          | *or*       | c           |              | chaffeensis* |
|          |            | haffeensis* | *or*         | or *A.       |
|          | dem        | DNA;        |              | phag         |
|          | onstration |             | id           | ocytophilum* |
|          | of *R.     | *or*        | entification | by PCR,      |
|          | r          |             | of morulae   | imm          |
|          | ickettsii* | ide         | in           | unostaining, |
|          | antigen in | ntification | leukocytes,  | or culture.  |
|          | a clinical | of morulae  | and a        |              |
|          | specimen   | in          | positive IFA |              |
|          | by IHC^5^  | leukocytes  | titer to *A. |              |
|          | methods;   | and a       | phag         |              |
|          |            | positive    | ocytophilum* |              |
|          | *or*       | IFA titer   | antigen;     |              |
|          |            | to *E.      |              |              |
|          | detection  | c           | *or*         |              |
|          | of *R.     | haffeensis* |              |              |
|          | r          | antigen;    | im           |              |
|          | ickettsii* |             | munostaining |              |
|          | DNA in a   | *or*        | of *A.       |              |
|          | clinical   |             | phag         |              |
|          | specimen   | imm         | ocytophilum* |              |
|          | by PCR     | unostaining | antigen in a |              |
|          | assay;     | of *E.      | biopsy or    |              |
|          |            | c           | autopsy      |              |
|          | *or*       | haffeensis* | sample;      |              |
|          |            | antigen in  |              |              |
|          | isolation  | a biopsy or | *or*         |              |
|          | of *R.     | autopsy     |              |              |
|          | r          | sample;     | culture of   |              |
|          | ickettsii* |             | *A.          |              |
|          | from a     | *or*        | phag         |              |
|          | clinical   |             | ocytophilum* |              |
|          | specimen   | culture of  | from a       |              |
|          | in cell    | *E.         | clinical     |              |
|          | culture.   | c           | specimen.    |              |
|          |            | haffeensis* |              |              |
|          |            | from a      |              |              |
|          |            | clinical    |              |              |
|          |            | specimen.   |              |              |
+----------+------------+-------------+--------------+--------------+
| **Case   | **Probable | **Probable  |              |              |
| classifi | case**:    | case**:     |              |              |
| cation** | Identified | Identified  |              |              |
|          | in a       | in a person |              |              |
|          | person     | with a      |              |              |
|          | with a     | clinically  |              |              |
|          | clinically | compatible  |              |              |
|          | compatible | illness     |              |              |
|          | illness    | with either |              |              |
|          | and        | a single    |              |              |
|          | serologic  | positive    |              |              |
|          | evidence   | IFA titer   |              |              |
|          | of         | (based on   |              |              |
|          | antibody   | cutoff      |              |              |
|          | reactive   | titers      |              |              |
|          | with *R.   | established |              |              |
|          | r          | by the      |              |              |
|          | ickettsii* | laboratory  |              |              |
|          | in a       | performing  |              |              |
|          | single     | the test)   |              |              |
|          | serum      | or the      |              |              |
|          | sample at  | vi          |              |              |
|          | a titer    | sualization |              |              |
|          | considered | of morulae  |              |              |
|          | indicative | in          |              |              |
|          | of current | leukocytes. |              |              |
|          | or         |             |              |              |
|          | previous   |             |              |              |
|          | infection  |             |              |              |
|          | (cutoff    |             |              |              |
|          | titers are |             |              |              |
|          | determined |             |              |              |
|          | by         |             |              |              |
|          | individual |             |              |              |
|          | labo       |             |              |              |
|          | ratories). |             |              |              |
+----------+------------+-------------+--------------+--------------+
| ** **    | *          |             |              |              |
|          | *Confirmed |             |              |              |
|          | case**:    |             |              |              |
|          | Identified |             |              |              |
|          | in a       |             |              |              |
|          | person     |             |              |              |
|          | with a     |             |              |              |
|          | clinically |             |              |              |
|          | compatible |             |              |              |
|          | illness    |             |              |              |
|          | that is    |             |              |              |
|          | laboratory |             |              |              |
|          | confirmed  |             |              |              |
|          | by a       |             |              |              |
|          | 4-fold     |             |              |              |
|          | change in  |             |              |              |
|          | serum      |             |              |              |
|          | antibody   |             |              |              |
|          | titer, as  |             |              |              |
|          | determined |             |              |              |
|          | by IFA or  |             |              |              |
|          | ELISA or   |             |              |              |
|          | positive   |             |              |              |
|          | PCR or     |             |              |              |
|          | positive   |             |              |              |
|          | IHC, or    |             |              |              |
|          | isolation  |             |              |              |
|          | in         |             |              |              |
|          | culture.   |             |              |              |
+----------+------------+-------------+--------------+--------------+

^1^ SOURCE: CDC. Rocky Mountain spotted fever (*Rickettsia rickettsii*):
2004 case definition. Atlanta, GA: US Department of Health and Human
Services, CDC, Epidemiology Program Office, Division of Public Health
Surveillance and Informatics; 2004.

^2^ SOURCE: CDC. Ehrlichiosis (HGE, HME, other or unspecified): 2000
case definition. Atlanta, GA: US Department of Health and Human
Services. CDC, Epidemiology Program Office, Division of Public Health
Surveillance and Informatics; 2000.

^3^ Indirect immunofluorescence antibody

^4^ Enzyme-linked immunosorbent assay

^5^ Immunohistochemical

^6^ Polymerase chain reaction

**Epidemiology of Tickborne Rickettsial Diseases (TBRD)**

The following is a summary of the salient epidemiologic features of
TBRD:

-   Occurrence is seasonal, with the majority of illness onset during
    warmer spring and summer months, but cases might develop throughout
    the year.

-   Rocky Mountain spotted fever (RMSF) has been reported in all of the
    contiguous 48 states, except Vermont and Maine.

-   RMSF and human monocytotropic (or monocytic) ehrlichiosis (HME) are
    most commonly reported in the southeastern and south central United
    States.

-   Human granulocytotropic (or granulocytic) anaplasmosis (HGA) is
    reported most frequently in New England, the north central states,
    and in focal areas along the West Coast.

**Pathogen Tropisms and Clinical Presentation**

The following is a summary of salient features of pathogen tropisms:

-   *Rickettsia. rickettsii* infects endothelial cells, causing
    vasculitis, which leads to rash and life-threatening damage to the
    brain, lungs, and other viscera.

-   *R. rickettsii* is not evident in blood smears, and these bacteria
    and do not stain with the majority of conventional stains.

-   *Ehrlichia* and *Anaplasma* species infect monocytes or
    granulocytes, respectively, and morulae might occasionally be
    observed on peripheral blood smears by using routine stains.

**Clues from the Clinical History**

The following is a summary of salient features of clues from the
clinical history:

-   A detailed history of recent recreational or occupational activities
    might reveal potential exposure to ticks.

-   Exposure can occur in the patient\'s backyard or neighborhood.

-   Familiarity with TBRD epidemiology will be helpful when querying
    patients regarding recent travel to endemic areas (domestic and
    international).

-   Clustering of certain TBRD is well-recognized and has been reported
    among family members, coworkers, and other defined groups.

**Clinical Assessment**

The following is a summary of salient clinical assessment features:

-   Early clinical presentations of HME, HGA, RMSF, and *Ehrlichia
    ewingii* infection include fever, headache, myalgia, and malaise and
    are difficult to distinguish from other infectious and noninfectious
    diseases.

-   Patients with RMSF typically do not have a spotted or petechial rash
    when they initially seek medical care during the first 2 to 4 days
    of illness.

-   A complete blood count (CBC), metabolic panel, and peripheral blood
    smear examination are helpful in developing both a differential
    diagnosis and treatment approach to TBRD.

-   Cerebrospinal fluid (CSF) analysis might reveal neutrophilic or
    lymphocytic pleocytosis and elevated protein but might not reliably
    distinguish TBRD and meningococcal disease, necessitating empiric
    antibiotic therapy for both conditions when indicated.

-   Leukopenia, thrombocytopenia, mild hyponatremia, and mildly elevated
    hepatic transaminase levels are common and particularly useful
    clinical features of TBRD, although the absence of these features
    does not exclude a diagnosis of TBRD.

-   Infrequent features of TBRD include severe abdominal pain and
    meningoencephalitis.

-   Rash is observed frequently in RMSF, occasionally in HME, and rarely
    in HGA or *E. ewingii* infection

**Treatment and Management**

The following is a summary of salient features of treatment and
management:

-   Clinical history, symptoms, and physical and laboratory findings
    should guide the clinician\'s approach to patient management and
    treatment.

-   Not all patients with TBRD will require hospitalization.

-   Clinicians may consider a wait and watch approach for 24 to 48 hours
    for patients early in the course of illness and who have
    nonsupporting history, nonspecific clinical signs, and normal
    laboratory findings.

-   Doxycycline is the drug of choice for the treatment of presumptive
    or confirmed TBRD in both adults and children.

-   Limited courses of tetracycline-class antibiotics (e.g.,
    doxycycline) do not pose a substantial threat of tooth staining in
    children.

-   Tetracyclines typically are contraindicated for use during pregnancy
    but might be warranted in life-threatening situations where clinical
    suspicion of TBRD is high.

-   Delay in treatment can lead to severe disease and fatal outcome of
    TBRD.

-   In evaluating for TBRD, when early invasive meningococcal infection
    cannot be ruled out, providing treatment for both conditions by
    adding an antimicrobial that has activity against *N. meningitidis*
    is appropriate.

-   Prophylactic use of antibiotics after a tick bite is not
    recommended.

**Considerations for Management of Patients with Severe Manifestations
of TBRD**

The following is a summary of salient features of severe manifestations:

-   TBRD can be life-threatening.

-   Severe manifestations of TBRD include prolonged fever, renal
    failure, myocarditis, meningoencephalitis, hypotension, acute
    respiratory distress syndrome, and multiple organ failure.

**Confirmatory Diagnostic Tests**

The following is a summary of salient features of diagnostic testing:

-   Blood smear microscopy might reveal presence of morulae in infected
    leukocytes, which is highly suggestive of HGA or, less commonly,
    HME.

-   Blood smears are not useful to diagnose RMSF.

-   Examination of paired serum samples obtained 2 to 3 weeks apart that
    demonstrate a rise in antibody titer is the most appropriate
    approach to confirm TBRD.

-   Patients usually do not have diagnostic serum antibody titers during
    the first week of illness; therefore, an inability to detect
    antibodies (IgG or IgM) in acute-phase serum does not exclude TBRD.

-   Immunohistochemistry of a biopsied skin lesion or autopsy tissues is
    useful for RMSF diagnosis in patients for whom diagnostic titers of
    antibodies have not yet developed.

-   Whole blood specimens might be useful for a polymerase chain
    reaction (PCR) confirmation of HME, HGA, and *E. ewingii* infection;
    however, a negative result does not rule out the diagnosis.

**Surveillance and Reporting**

The following is a summary of salient features of surveillance and
reporting:

-   RMSF, HME, HGA, and other ehrlichioses are reportable diseases in
    the United States.

-   Physicians who identify a potential case of TBRD should notify the
    local health department, which can assist with obtaining diagnostic
    testing to confirm the diagnosis.

-   Surveillance and reporting of TBRD are key components of public
    health education and disease prevention efforts.

**Prevention**

The following is a summary of salient features of prevention:

-   Avoid tick bites, which is key to the prevention of TBRD.

-   Limit exposure to tick habitats, including grassy and wooded areas.

-   Inspect the body carefully for ticks after being in a tick habitat.

-   Remove attached ticks immediately by grasping with tweezers close to
    skin and pulling gently with steady pressure.

**Conclusion**

TBRD continue to cause severe illness and death in otherwise healthy
adults and children, despite the availability of low cost, effective
antimicrobial therapy. The greatest challenge to clinicians is the
difficult diagnostic dilemma posed by these infections early in their
clinical course when antibiotic therapy is most effective.

Early clinical presentations of HME, HGA, RMSF, and *E. ewingii*
infection include fever, headache, myalgia, and malaise and are
difficult to distinguish from other infectious and noninfectious
diseases. Rash is observed frequently in RMSF, occasionally in HME, and
rarely in HGA. TBRD tend to occur seasonally, with the majority of cases
occurring during the warmer spring and summer months. However, cases
might develop year-round. A detailed history of recent recreational or
occupational activities might reveal potential exposure to ticks,
although the absence of a history of a recent tick bite should not
dissuade clinicians from considering a diagnosis of TBRD.

TBRD can be life-threatening. Severe manifestations of TBRD include
prolonged fever, renal failure, myocarditis, meningoencephalitis,
hypotension, acute respiratory distress syndrome, and multiple organ
failure. Patients usually do not have diagnostic serum antibody levels
during the first week of illness; therefore, an inability to detect
antibodies (IgG or IgM) in acute-phase serum does not exclude TBRD.
Health-care providers should not delay treatment while waiting for a
diagnosis; rather, they should empirically provide treatment if they
suspect TBRD. Doxycycline is the drug of choice for the treatment of
presumptive or confirmed TBRD in both adults and children.

Examination of paired serum samples obtained during acute illness and 2
to 3 weeks later that demonstrate a rise in antibody titer is the most
appropriate approach to confirm TBRD. Physicians who identify a
potential case of TBRD should notify the local health department, which
can assist with obtaining diagnostic testing to confirm the diagnosis.

No licensed vaccines for TBRD are available. Avoiding tick bites and
promptly removing attached ticks remain the best disease prevention
strategies.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of evidence supporting the recommendations is not specifically
stated.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

-   Improved recognition of common epidemiologic situations and clinical
    manifestations of tickborne rickettsial diseases (TBRD)

-   Application of appropriate history and diagnostic tests for TBRD

-   Prevention of severe morbidity and death by early and empiric
    antibiotic therapy

-   Improved surveillance and reporting of TBRD

#### POTENTIAL HARMS

-   The propensity of tetracyclines to bind calcium can lead to
    darkening of the teeth if the antibiotic is ingested during the
    period of tooth crown formation. More recent studies in 1971 and
    1998, however, have demonstrated that although multiple exposures to
    tetracycline increase the risk for tooth staining, limited use of
    this drug in children during the first 6 to 7 years of life has a
    negligible effect on the color of permanent incisors. Beyond ages 6
    to 7 years, the risk for tetracycline staining is of minimal
    consequence because visible tooth formation is complete.

-   Chloramphenicol is associated with various side effects and might
    require monitoring of blood indices. Chloramphenicol is no longer
    available in the oral form in the United States. Moreover,
    epidemiologic studies in which the Centers for Disease Control and
    Prevention (CDC) case report data have been used suggested that
    patients with Rocky Mountain spotted fever treated with
    chloramphenicol have a higher risk of dying than persons who
    received a tetracycline.

-   Whereas chloramphenicol is typically the preferred treatment for
    Rocky Mountain spotted fever during pregnancy, care must be used
    when administering chloramphenicol late during the third trimester
    of pregnancy because of risks associated with grey baby syndrome.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

Tetracyclines are generally contraindicated for use in pregnant women
because of risks associated with malformation of teeth and bones in the
fetus and hepatotoxicity and pancreatitis in the mother. However,
tetracycline has been used successfully to treat human monocytotropic
(or monocytic) ehrlichiosis in pregnant women, and the use of
tetracyclines might be warranted during pregnancy in life-threatening
situations where clinical suspicion of tickeborne rickettsial diseases
is high.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Chart Documentation/Checklists/Forms\
Staff Training/Competency Material

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Staying Healthy

#### IOM DOMAIN

Effectiveness\
Timeliness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Chapman AS, Bakken JS, Folk SM, Paddock CD, Bloch KC, Krusell A, Sexton
DJ, Buckingham SC, Marshall GS, Storch GA, Dasch GA, McQuiston JH,
Swerdlow DL, Dumler SJ, Nicholson WL, Walker DH, Eremeeva ME, Ohl CA.
Diagnosis and management of tickborne rickettsial diseases: Rocky
Mountain spotted fever, ehrlichioses, and anaplasmosis\--United States:
a practical guide for physicians and other health-care and public health
professionals. MMWR Recomm Rep 2006 Mar 31;55(RR-4):1-27. \[104
references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16572105)

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2006 Mar 31

#### GUIDELINE DEVELOPER(S)

Centers for Disease Control and Prevention - Federal Government Agency
\[U.S.\]

#### SOURCE(S) OF FUNDING

United States Government

#### GUIDELINE COMMITTEE

Tickborne Rickettsial Diseases Working Group

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Prepared by*: Alice S. Chapman, DVM, National Center for Infectious
Diseases, CDC

*Working Group Members*: Johan S. Bakken, MD, PhD, St. Luke\'s
Infectious Disease Associates, Duluth, Minnesota; Karen C. Bloch, MD,
Vanderbilt University Medical School, Nashville, Tennessee; Steven C.
Buckingham, MD, University of Tennessee Health Science Center, Memphis,
Tennessee; Gregory A. Dasch, PhD, National Center for Infectious
Diseases, CDC; J. Stephen Dumler, MD, Johns Hopkins Medical
Institutions, Baltimore, Maryland; Marina E. Eremeeva, MD, PhD, ScD,
National Center for Infectious Diseases, CDC; Scott M. Folk, MD,
Heartland Regional Medical Center, St. Joseph, Missouri; Allan Krusell,
MD, Northeast Medical Center, Concord, North Carolina; Gary S. Marshall,
MD, University of Louisville Medical School, Louisville, Kentucky;
Jennifer H. McQuiston, DVM, National Center for Infectious Diseases,
CDC; William L. Nicholson, PhD, National Center for Infectious Diseases,
CDC; Christopher A. Ohl, MD, Wake Forest University Medical School,
Winston-Salem, North Carolina; Christopher D. Paddock, MD, National
Center for Infectious Diseases, CDC; Daniel J. Sexton, MD, Duke
University Medical School, Durham, North Carolina; Gregory A. Storch,
MD, Washington University Medical School, St. Louis, Missouri; David L.
Swerdlow, MD, National Center for Infectious Diseases, CDC; David H.
Walker, MD, University of Texas Medical Branch, Galveston, Texas

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

The Centers for Disease Control and Prevention (CDC), their planners,
and their content experts wish to disclose they have no financial
interests or other relationships with the manufacturers of commercial
products, suppliers of commercial services, or commercial supporters.
Presentations will not include any discussion of the unlabeled use of a
product or a product under investigational use.

#### GUIDELINE STATUS

This is the current release of the guideline.

#### GUIDELINE AVAILABILITY

Electronic copies: Available from the Centers for Disease Control and
Prevention (CDC) Web site:

-   [HTML Format](http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5504a1.htm)

-   [Portable Document Format
    (PDF)](http://www.cdc.gov/mmwr/PDF/rr/rr5504.pdf)

Print copies: Available from the Centers for Disease Control and
Prevention, MMWR, Atlanta, GA 30333. Additional copies can be purchased
from the Superintendent of Documents, U.S. Government Printing Office,
Washington, DC 20402-9325; (202) 783-3238.

#### AVAILABILITY OF COMPANION DOCUMENTS

A case report form (for tick-borne rickettsial disease \[TBRD\]) and a
continuing education activity are available in the appendix of the
[original guideline
document](http://www.cdc.gov/mmwr/PDF/rr/rr5504.pdf).

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on May 5, 2006.

#### COPYRIGHT STATEMENT

No copyright restrictions apply.

### DISCLAIMER

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Date Modified: 11/10/2008