Rickettsia typhi - Typhus Fever

Indications for Testing

Febrile illness in setting of unhygienic environments

Laboratory Testing

Non-specific
- CBC
- Hepatic transaminases
- Bilirubin
- Blood urea nitrogen (BUN)
IgG and IgM by IFA – method of confirming diagnosis
- Convalescent specimen usually required
- IgG does not differentiate between primary infection and Brill-Zinsser disease
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 – not sensitive or specific; outmoded; should not be used
Culture – not routinely available because of biosafety issues (research labs only)

Differential Diagnosis

Other rickettsial diseases
Babesia microti
Ehrlichiosis
Borrelia burgdorferi
Francisella tularensis
Plasmodium spp
Salmonella typhi (typhoid fever)
Leptospira spp
Treponema pallidum (secondary syphilis)
Dengue fever virus
Toxoplasma gondii

Rickettsia typhi is the etiologic agent of both epidemic and endemic typhus.

Epidemiology

Incidence – <100 cases annually in the U.S.
Transmission – louse or flea-borne

Organism

Gram-negative coccobacilli of the Rickettsiaceae family (obligate intracellular organisms)
Characteristic feature of Rickettsia – life cycle requires multiplying in an arthropod
With typhus (Rickettsia prowazekii and R. typhi), the 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

Epidemic typhus (louse-borne) – common in poor hygienic areas (eg, jails) in cold months
Endemic murine typhus (flea-borne) – common in close-quartered poverty in warm climates
Recrudescent typhus (Brill-Zinsser disease) – previously acquired disease that results from immunosuppression or old age
Flying squirrels – particularly in southern U.S.

Clinical Presentation

The incubation period for most rickettsioses ranges from 3-14 days
Most patients develop nonspecific symptoms and signs
Onset of disease is sudden in about half of the cases
- Fever and headache are the most commonly reported symptoms, but chills, myalgias, arthralgias, malaise and anorexia also are noted
- Rash (maculopapular, nonconfluent and blanching areas) is a hallmark of infection, but it usually follows systemic symptoms
  - Its absence should not rule out a possible rickettsial etiology
Pulmonary involvement is frequent in murine typhus
Serious central nervous system impairment can also be seen with typhus
- Meningitis
- Seizures
- Hearing loss

Treatment

Antibiotic treatment is curative

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

Test name: Rickettsia typhi (Typhus Fever) Antibodies, IgG & IgM by IFA

ARUP #: 0050384

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Use:

Confirm presence of Rickettsia typhi

Limitations:

Initial testing may not be helpful; base treatment on clinical and other laboratory assessment

While the presence of IgM antibodies suggests current or recent infection, low levels of IgM antibodies may occasionally persist for >12 months post-infection

Any antibody reactivity to Rickettsia typhi antigen should also be considered group reactive for the typhus fever group (R. prowazekii)

Follow-up:

If test results are equivocal, repeat testing in 10-14 days

Test name: Febrile Antibodies Panel

ARUP #: 2001789

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

Use:

Use to confirm presence of disease; not recommended for initial testing

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

Limitations:

Base treatment decision on clinical and other laboratory assessments

Cross reactivity with Brucella and Salmonella

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Non-specific testing for R. typhi

Shows thrombocytopenia in 40% of cases

Test name: Urea Nitrogen, Serum or Plasma

ARUP #: 0020023

Methodology: Quantitative Spectrophotometry