Clinical and Laboratory Diagnosis

Clinical Diagnosis

  • Early recognition and treatment with doxycycline is critical to survival.
  • Rocky Mountain spotted fever (RMSF) can be difficult to diagnose due to the non-specific signs and symptoms in early stages of illness. Signs and symptoms can vary from patient to patient and can resemble other, more common diseases. Nonetheless, early consideration of rickettsial disease in the differential diagnosis and empiric treatment is crucial to prevent severe illness and death.
  • Always take a thorough patient history, including:
    • Recent tick bite. NOTE: Tick bites are often painless. Many people do not remember being bitten. Do not rule out a tickborne infection if your patient does not remember a tick bite.
    • Exposure to areas where ticks are commonly found, including wooded areas or brushy areas with high grasses and leaf litter. In Arizona and Mexico, ask about exposure to dogs.
    • Travel history (domestic and international) to areas where RMSF is endemic.
  • Maintain clinical suspicion of RMSF for cases of non-specific febrile illness and sepsis of unknown origin, particularly during spring and summer months when ticks are most active.
  • Laboratory confirmation is helpful for disease surveillance and understanding burden of RMSF infection in the United States, but should not be relied upon to make a treatment decision.

The decision to initiate antibiotic therapy for RMSF should be made based on clinical signs and symptoms and a careful patient history, including a recent tick bite or exposure to areas with ticks. A confirmatory diagnosis can be established later using specialized laboratory tests. Never delay or withhold treatment pending the receipt of laboratory test results, or on the basis of an initially negative result.

Laboratory Diagnosis

Rickettsial Diseases in the United States video thumbnail

Rickettsial Disease Diagnostic Testing and Interpretation for Healthcare Providers

This video provides information on rickettsial disease diagnostic methods for healthcare providers, including what tests are available and when it is most appropriate to collect samples. This video focuses on the use of polymerase chain reaction (or PCR) tests, and the indirect immunofluorescence antibody (IFA) assay for rickettsial disease diagnosis.

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Access the Fact Sheet pdf icon[PDF – 1 page]

  • Order diagnostic tests for patients with illness clinically compatible with RMSF. However, do not delay treatment while waiting for diagnostic test results.
  • The optimal diagnostic test depends on the timing relative to symptom onset and the type of specimen(s) available for testing.
  • Testing for RMSF should be considered for any person with a compatible illness and known risk factors, such as:
    • Those who remember a tick bite or have been exposed to areas with ticks
  • RMSF is a nationally notifiable condition. Correct testing and reporting of RMSF is important to improve understanding of how common this disease is, where it occurs, and how disease trends change over time.


  • The standard serologic test for diagnosis of RMSF is the indirect immunofluorescence antibody (IFA) assay for immunoglobulin G (IgG) using R. rickettsii antigen.
  • IgG IFA assays should be performed on paired acute and convalescent serum samples collected 2–4 weeks apart to demonstrate evidence of a fourfold seroconversion.
  • Antibody titers are frequently negative in the first week of illness. RMSF cannot be confirmed using single acute antibody results.
  • Immunoglobulin M (IgM) IFA assays are available through some reference laboratories, however results might be less specific than IgG IFA assays for diagnosing a recent infection.
  • R. rickettsii is closely related to other pathogenic spotted fever group Rickettsia (SFGR) species, including R. akari, R. parkeri, and Rickettsia 364D. Closely related species of SFGR share similar antigens such that antibodies directed to one of these antigens can cross-react with other heterologous spotted fever group antigens.
  • Most commercial labs are unable to differentiate one spotted fever infection from another using these serologic methods.

Persistent Antibodies

  • Antibodies to R. rickettsii might remain elevated for many months after the disease has resolved.
  • In certain people, high titers of antibodies against R. rickettsii have been observed up to four years after the acute illness.
  • Ten percent or more of healthy people in some areas might have elevated antibody titers due to past exposure to R. rickettsii or other SFGR.
  • Comparison of paired, and appropriately timed, serologic assays provides the best evidence of recent infection.
  • Single or inappropriately timed serologic tests, in relation to clinical illness, can lead to misinterpretation of results.


  • Polymerase chain reaction (PCR) amplification is performed on DNA extracted from whole blood.
  • R. rickettsii infect the endothelial cells that line blood vessels and may not circulate in large numbers in the blood until the disease has progressed to a severe phase of infection.
  • Although a positive PCR result is helpful, a negative result does not rule out the diagnosis, and treatment should not be withheld due to a negative result.
  • PCR might also be used to amplify DNA from a skin biopsy of a rash lesion, or in post-mortem tissue specimens. See instructions for the collection of a skin biopsy pdf icon[PDF – 1 page].

IHC and Culture

  • Culture and immunohistochemistry (IHC) assays can also be performed on skin biopsies of a rash lesion, or post-mortem tissue specimens.
  • Culture isolation and IHC assays of R. rickettsii are only available at specialized laboratories; routine hospital blood cultures cannot detect the organism.

For more in-depth information about diagnostic testing, see: 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 (2016) pdf icon[PDF – 48 pages]