Rickettsia rickettsii - Rocky Mountain Spotted Fever

Indications for Testing

Flu-like illness with or without rash in association with tick bite exposure and proper epidemiologic setting

Laboratory Testing

Diagnosis is made based upon clinical grounds with history of tick exposure
- Definitive diagnosis made only retrospectively using serology
Serology
- The best evidence for infection is a significant change in 2 appropriately timed specimens where both tests are done in the same laboratory at the same time
  - Appearance of an IgM antibody response by IFA or ELISA normally occurs 7-14 days after the onset of disease
    - Not usually detectable by day 5 (when fatality starts to rise dramatically)
  - Negative initial IgM does not exclude the disease
  - Cannot distinguish between cross-reacting Rickettsiae
- Consider concurrent testing for similar illnesses – human monotropic ehrlichiosis, Neisseria species, Borrelia burgdorferi
Febrile antibody testing
- More specific than Weil-Felix but still has cross-reactivity with Brucella and Salmonella
- Must be used in conjunction with clinical presentation
Weil-Felix – lacks sensitivity and specificity; do not use
Blood culture – research labs only
- Highly sensitive and specific

Histology

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
- Disseminated gonococcus, meningococcus
- Kawasaki disease
- Borrelia burgdorferi
- Parvovirus B19
- Rickettsia typhi
- Treponema pallidum (secondary syphilis)
- Dengue fever
- Human monotropic ehrlichiosis
Pneumonia/influenza
- Mycoplasma pneumoniae
Meningoencephalitis
- Epstein-Barr virus
- Leptospira species
- Borrelia burgdorferi
- Vasculitis
- Human granulocytic anaplasmosis
- Human monotropic ehrlichiosis
- Dengue fever
Myocarditis
- Enterovirus
- Epstein-Barr virus
- Mycoplasma pneumoniae
Gastroenteritis
- Clostridium difficile
- Diarrhea, bacterial
- Diarrhea, viral
- Enterovirus

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

Epidemiology

Incidence – 3-5/1,000,000
Age – peak incidence 5-9 years
Transmission
- Via Dermacentor (variabilis, andersoni), Amblyomma, and Rhipicephalus sanguineus ticks in the U.S.
  - Geographical distribution is restricted to the western hemisphere
- Humans are accidental hosts
- 95% of the cases occur April through September

Organism

Gram-negative coccobacilli of the Rickettsiaceae family – obligate intracellular organisms
Characteristic feature of the Rickettsiae – life cycle requires multiplying in an arthropod
Invertebrate hosts are both reservoirs and vectors
Rickettsia are part of a family of organisms responsible for the following rickettsial diseases
- Spotted fever and typhus (vector: tick, louse, flea or gamasid mite)
- Scrub typhus (vector: chigger)
- Ehrlichiosis (vector: tick)
- Neorickettsiosis
- Q-fever

Risk Factors

Dog exposure to ticks
Residence in a wooded area
Residence in Central and Mid-Atlantic states
Male sex

Clinical Presentation

The incubation period between tick bite and onset of symptoms is 2-14 days
RMSF is difficult to differentiate from viral illness
Non-specific signs and symptoms
- Classic triad – fever, headache and rash
- Rash typically appears on the second or third day of illness
  - Rash begins as macules on the wrists, palms, ankles and soles of feet, which then results in petechiae form
  - Rash finally spreads to the trunk
  - Rash is hallmark of infection but usually follows systemic symptoms; its absence should not rule out a possible rickettsial etiology
Other symptoms include malaise, myalgias, vomiting and photophobia
- Mild pulmonary involvement, manifested by cough and infiltrates, is found in about one-third of patients with RMSF
Neurologic (25% of patients)
- Meningitis
- Meningoencephalitis
- Seizures
- Confusion
- Focal neurologic deficits
Cardiovascular
- Myocarditis
- Pericarditis
Mortality is dependent on cardiac and central nervous system involvement or delay in treatment

Treatment

Initiation of early antibiotic therapy is necessary to reduce mortality
- Decision to treat should not be delayed until lab confirmation of organism

Tests generally appear in the order most useful for common clinical situations

Test name: Rickettsia rickettsii (Rocky Mountain Spotted Fever) Antibodies, IgG & IgM by IFA

ARUP #: 0050371

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Use:

Confirm infection with Rickettsia rickettsii (Rocky Mountain Spotted Fever)

Acute and convalescent titers often necessary

Limitations:

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

Initial testing may not be helpful; determine treatment from clinical and other laboratory assessments

Any antibody reactivity to R. rickettsii should also be considered group reactive for the spotted fever group (R. conorii, R. honei, R. akari, R. japonica, R. australis, and R. sibirica)

Test name: Febrile Antibodies Panel

ARUP #: 2001789

Methodology: Semi-Quantitative Direct Agglutination/Semi-Quantitative Indirect Fluorescent Assay/Qualitative ImmunoDOT

Use:

Aids in confirming presence of Rocky Mountain Spotted Fever; not recommended for initial testing

Panel includes IgM R. rickettsii antibody by ELISA testing, as well as testing for antibodies to Brucella, Rickettsia typhi, Salmonella O and H

Limitations:

Initial testing may not be helpful; determine treatment from clinical and other laboratory assessments

Additional Tests Available

Test name: Rickettsia rickettsii (Rocky Mountain Spotted Fever) Antibody, IgG

ARUP #: 0050369

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Rickettsia rickettsii (Rocky Mountain Spotted Fever) Antibody, IgM

ARUP #: 0050372

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Weil-Felix Test