Rickettsia rickettsii - Rocky Mountain Spotted Fever

Rickettsia rickettsii is a tick-borne illness (zoonosis) among the spotted fever group rickettsioses and is the etiologic agent of Rocky Mountain Spotted Fever (RMSF).


Indications for Testing

  • Tick bite exposure and relevant epidemiologic setting
  • Fever, headache, myalgia, nausea, vomiting; rash 2-5 days after fever

Laboratory Testing

  • Diagnosis and laboratory confirmation recommendations (CDC)
  • Antibiotic therapy should be initiated in the event of clinical suspicion, before testing, and not discontinued even if results are negative
  • Diagnosis
    • IgG and IgM testing
      • Significant increase in immunoglobulins in samples taken during both acute and convalescent stages using indirect fluorescent antibody (IFA) testing confirms diagnosis (retrospective confirmation; should not be used to make treatment decisions)
      • IgM antibody does not usually appear until 7-14 days after disease onset and is less specific than IgG
      • Cannot distinguish between cross-reacting antibodies generated against other spotted fever group Rickettsia spp
    • Other testing
      • CBC may show thrombocytopenia
      • Sodium levels may be decreased in more severe disease
      • Alanine​ aminotransferase (ALT) and aspartate aminotransferase (AST) may be slightly elevated


  • Immunohistochemistry – direct immunofluorescence or immunoperoxidase tests on skin biopsies
    • Sensitivity ~70%; specificity 100%
    • Testing not widely available
    • Negative result does not rule out disease

Differential Diagnosis

  • Rash
    • Consider patient’s locale and recent travel, as some diagnoses can be excluded on geographic basis



  • Incidence – 3-5/million
  • Age – peak incidence 5-9 years
  • Transmission
    • Dermacentor (D. variabilis, D. andersoni) and Rhipicephalus sanguineus ticks in the U.S.
    • Humans are accidental hosts
    • 95% of cases occur April through September


Gram-negative obligate intracellular coccobacilli of the Rickettsiaceae family

Risk Factors

  • Bite from an infected tick
  • Residence in a wooded area
  • Residence in or travel to Central, mid-Atlantic, and Southern U.S. states

Clinical Presentation

  • Symptom onset – 2-14 days after tick bite (incubation period)
  • Difficult to differentiate from viral illness
  • Nonspecific signs and symptoms
    • Classic triad – fever, headache, and rash
    • Rash typically appears on second or third day of illness
      • Begins as small, pink macules on wrists, palms, ankles, and soles of feet – might include petechiae
      • Spreads to trunk
      • Usually follows systemic symptoms – absence should not rule out possible rickettsial etiology
  • Other symptoms – malaise, myalgia, abdominal pain, vomiting, and photophobia
  • Untreated disease can lead to major organ dysfunction
  • Mortality – extremely rare
    • Dependent on cardiac and central nervous system involvement or delay in treatment



Fatality rate higher in children than adults, especially in children <10 years.

Clinical Presentation

  • Nausea, vomiting, fever, rash, loss of appetite, abdominal pain
  • May have swelling of hands

ARUP Laboratory Tests

Preferred test for acute or convalescent phase of disease

Acute and convalescent titers often necessary

Low-positive results suggest past exposure or infection, whereas high-positive results may indicate recent or past infection but are inconclusive for diagnosis

Related Tests

Detect antibodies during convalescent phase

Detect antibodies during acute phase; paired concurrent specimen with IgG reduces false-positive rate

Convalescent sera may be required for diagnosis

Medical Experts



Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories


Additional Resources