Rickettsia typhi - Typhus Fever

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Febrile illness in setting of unhygienic environments

Laboratory Testing

  • Clinical presentation and diagnosis recommendations (CDC)
  • Nonspecific
    • 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

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:

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 recurs most often 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 can be present
    • Rash (maculopapular, nonconfluent, and blanching areas) is a hallmark of infection, but it usually follows systemic symptoms
      • Often transient and difficult to observe in murine typhus
      • 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
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Rickettsia typhi (Typhus Fever) Antibodies, IgG & IgM by IFA 0050384
Method: Semi-Quantitative Indirect Fluorescent Antibody

Recommended Use 

Confirm presence of Rickettsia typhi

Requires comparison of acute- to convalescent-phase serology

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 postinfection

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

Febrile Antibodies Identification Panel 2010805
Method: Semi-Quantitative Agglutination/Semi-Quantitative Indirect Fluorescent Antibody/Qualitative Immunoblot

Recommended Use 

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

Panel includes Brucella Antibody (Total) by Agglutination; Rickettsia rickettsii Antibody, IgM; Rickettsia rickettsii antibody, IgG; Rickettsia typhi Antibody, IgG by IFA; Rickettsia typhi Antibody, IgM by IFA, and Salmonella typhi and paratyphi Antibodies

Limitations 

Base treatment decision on clinical and other laboratory assessments

Cross reactivity with Brucella and Salmonella

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Recommended Use 

Nonspecific testing for R. typhi

Shows thrombocytopenia in 40% of cases

Urea Nitrogen, Serum or Plasma 0020023
Method: Quantitative Spectrophotometry

Recommended Use 

Screening test to evaluate kidney function

Nonspecific testing for R. typhi

Elevated in ~30% of cases

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Recommended Use 

Initial screening for hepatobiliary inflammation

Panel includes albumin; ALP; AST; ALT; bilirubin, direct; protein, total; and bilirubin, total

Nonspecific testing for R. typhi

Bilirubin elevated in ~20% of cases

Creatinine, Serum or Plasma 0020025
Method: Quantitative Enzymatic

Recommended Use 

Screening test to evaluate kidney function

Nonspecific testing for R. typhi

Limitations 

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

Guidelines

Chapman AS, Bakken JS, Folk SM, Paddock CD, Bloch KC, Krusell A, Sexton DJ, Buckingham SC, Marshall GS, Storch GA, Dasch GA, McQuiston JH, Swerdlow DL, Dumler SJ, Nicholson WL, Walker DH, Eremeeva ME, Ohl CA, Tickborne Rickettsial Diseases Working Group, CDC. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep. 2006; 55(RR-4): 1-27. PubMed

Huntzinger A. Guidelines for the Diagnosis and Treatment of Tick-Borne Rickettsial Diseases. American Cancer Society. Leawood, KS [Accessed: Jun 2015]

General References

Bechah Y, Capo C, Mege J, Raoult D. Epidemic typhus. Lancet Infect Dis. 2008; 8(7): 417-26. PubMed

Brouqui P, Raoult D. Arthropod-borne diseases in homeless. Ann N Y Acad Sci. 2006; 1078: 223-35. PubMed

Civen R, Ngo V. Murine typhus: an unrecognized suburban vectorborne disease. Clin Infect Dis. 2008; 46(6): 913-8. PubMed

Delord M, Socolovschi C, Parola P. Rickettsioses and Q fever in travelers (2004-2013). Travel Med Infect Dis. 2014; 12(5): 443-58. PubMed

Walker DH, Paddock CD, Dumler S. Emerging and re-emerging tick-transmitted rickettsial and ehrlichial infections. Med Clin North Am. 2008; 92(6): 1345-61, x. PubMed

Medical Reviewers

Couturier, Marc Roger, PhD, D(ABMM), Medical Director, Microbial Immunology, Parasitology and Fecal Testing, and Infectious Disease Rapid Testing at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Last Update: August 2016

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