Rickettsia typhi - Typhus Fever

Rickettsia typhi is the etiologic agent of both epidemic and endemic typhus. Serologic testing is used to confirm the diagnosis and requires acute- and convalescent-phase serum samples.

Diagnosis

Indications for Testing

Fever, headache, chills, rash, dry cough, nausea, and vomiting in at-risk individual (living in unsanitary conditions, close human contact, with potential for mouse/rat contact)

Laboratory Testing

  • Clinical presentation and diagnosis recommendations (CDC)
  • Nonspecific
    • CBC
    • Hepatic transaminases
    • Bilirubin
    • Blood urea nitrogen (BUN)
    • Creatinine
  • IgG and IgM by indirect fluorescent antibody (IFA) – use to confirm 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

Background

Epidemiology

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

Organism

  • Gram-negative coccobacilli of the Rickettsiaceae family (obligate intracellular organisms)
  • Characteristic feature of Rickettsia – life cycle requires multiplying in an arthropod
  • With typhus (R. 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) – residence in poor hygienic areas (eg, jails) in cold months
  • Endemic murine typhus (flea borne) – residence in close-quartered poverty in warm climates
  • Recrudescent typhus (Brill-Zinsser disease) – previously acquired disease combined with immunosuppression or old age
  • Flying squirrel typhus (louse or flea borne) – contact with flying squirrels, particularly in southern U.S.

Clinical Presentation

  • Incubation period – 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
    • Chills, myalgias, arthralgias, malaise, and anorexia can be present
    • Rash (maculopapular, nonconfluent, and blanching areas)
      • Hallmark of infection
      • Usually follows systemic symptoms
      • Often transient and difficult to observe in murine typhus
      • 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
    • Multiorgan failure may occur

ARUP Lab Tests

Confirm presence of Rickettsia typhi

Not recommended for initial testing; requires comparison of acute- to convalescent-phase serology

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

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

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

Confirm presence of disease

Not recommended for initial testing

Panel includes total Brucella antibody by agglutination; R. rickettsii antibody, IgM; R. rickettsii antibody, IgG; R. typhi antibody, IgG by indirect fluorescent antibody (IFA); R. typhi antibody, IgM by IFA, and Salmonella typhi and paratyphi antibodies

Nonspecific testing for R. typhi

Initial screening for hepatobiliary inflammation

Nonspecific testing for R. typhi

Panel includes albumin; alkaline phosphatase (ALP); aspartate aminotransferase (AST); alanine aminotransferase (ALT); bilirubin, direct; protein, total; and bilirubin, total

Screening test to evaluate kidney function

Nonspecific testing for R. typhi

Screening test to evaluate kidney function

Nonspecific testing for R. typhi

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite), but only when concentrations are at or above those expected during acetaminophen overdose

Related Tests

Confirm presence of R. typhi

Panel test (IgG and IgM) is preferred

Requires comparison of acute- to convalescent-phase serology

Medical Experts

Contributor

Couturier

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

References

Additional Resources