Rickettsial Infection Workup

Updated: Nov 22, 2021
  • Author: Mobeen H Rathore, MD, CPE, FAAP, FIDSA; Chief Editor: Russell W Steele, MD  more...
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Laboratory Studies

Rickettsiae are not evident on blood smear findings and do not stain with most conventional stains. [3, 4]

No rapid laboratory tests are available to diagnose rickettsial diseases early in the course of illness.

Serologic assays that demonstrate antibodies to rickettsial antigens (eg, indirect immunofluorescence, complement fixation, indirect hemagglutination, latex fixation, enzyme immunoassay, microagglutination) are preferable to the nonspecific and insensitive Weil-Felix test based on the cross-reactive antigens of Proteus vulgaris strains. Serologic findings usually take 10-12 days to become positive. The value of testing 2 sequential serum or plasma samples together to show a rising antibody level is considerably more important in confirming acute infection with rickettsial agents because antibody titers may persist in some patients for years after the original exposure.

Immunofluorescence assay (IFA) is currently considered to be the reference serological method. However, it cannot determine the causative agent to the species level.

Polymerase chain reaction (PCR) to detect rickettsiae in blood or tissue provides promise for early diagnosis. PCR testing and immunohistochemical staining of skin specimen obtained by performing a biopsy may help confirm the clinical diagnosis in patients with rash (high expertise is usually needed to interpret the biopsy result).

Preliminary findings of new research is indicating that swabs of eschars may be used for molecular detection of rickettsial infections when biopsies are difficult to perform. [33, 34, 35] However, serology remains the mainstay of diagnosis because these other tests are expensive and less available to clinicians.

Rickettsial isolation in culture is unnecessary, laborious, and hazardous to laboratory personnel.

Rocky Mountain spotted fever (RMSF)

Serology is the mainstay to confirm diagnosis.

Another approach to RMSF diagnostics is immunostaining whereby a skin biopsy of the rash from an infected patient is tested prior to therapy or within the first 48 hours after antibiotic therapy has been started. This test's use remains highly operator-dependent.

Other tests, such as PCR, are rather expensive and not readily available.

Nonspecific laboratory findings, such as thrombocytopenia, leukopenia, and mild hyponatremia, may give helpful clues to the treating physician.

If cerebrospinal fluid is examined, pleocytosis (generally < 100 cells/μ L) is typically observed with polymorphonuclear or lymphocyte predominance, moderately elevated protein levels (100-200 mg/dL), and normal glucose levels.


As with other rickettsial infections, diagnosis is clinical and may be confirmed by serology.

The Weil-Felix test is not useful because R akari does not produce Weil-Felix agglutinins.

R akari has a soluble antigen that cross-reacts with R rickettsii (the cause of RMSF) and other spotted fever groups of rickettsiae.

Boutonneuse fever

Serologic laboratory confirmation (complement fixation, microagglutination, western blot, indirect immunofluorescent tests) usually provides support for the diagnosis made on clinical and epidemiologic grounds. Additionally, a latex agglutination test for detection of antibodies to R conorii that is both specific and sensitive now can be performed in specialized laboratories.

R conorii has been detected from the tache noire by restriction fragment length polymorphism (RFLP) and by PCR. [10]

Louse-borne (epidemic) typhus

Serologic laboratory confirmatory tests are available as in RMSF. Patients initially have an IgM response followed by production of immunoglobulin G (IgG) antibodies.

However, a significant antigenic crossing is noted between this rickettsial organism and those of the spotted fever group.

PCR promises to be a rapid diagnostic test but is expensive and not yet widely available.

Brill-Zinsser disease (ie, relapsing louse-borne typhus)

Laboratory studies are similar to those for primary louse-borne epidemic typhus. However, patients develop an anamnestic immune response whereby only IgG is produced.

Murine (endemic or flea-borne) typhus

Laboratory studies are analogous to those mentioned for epidemic louse-borne typhus.

Additionally, a mild-to-moderate elevation of serum aspartate aminotransferase (AST) level is present in approximately 90% of patients. Other indices of hepatocellular injury (alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase) are often also elevated.

Tsutsugamushi disease (ie, scrub typhus)

Serologic testing using specific methods (eg, immunofluorescence antibody test, indirect immunoperoxidase test, enzyme immunoassay) is superior to the Weil-Felix reaction.

However, these tests are cumbersome and only available in a few special laboratories.

Q fever

Laboratory findings in acute Q fever infection may include thrombocytopenia in approximately 25% of cases and elevated hepatic transaminases. In prolonged infections, autoantibodies (eg, anti-smooth muscle antibodies) may be found. [5]

In addition to clinical and epidemiologic features, serology (eg, microimmunofluorescence, complement fixation, enzyme immunoassay) remains the mainstay of diagnosis in acute and chronic illnesses.

As with other rickettsiae, attempts to isolate the organism are biohazardous and unnecessary.

PCR may be used; however, it remains less available and more expensive than serology.

Chronic Q fever endocarditis is diagnosed by demonstration of high antibody (IgG and IgA) titers against C burnetii in patients with signs of endocarditis whose blood cultures contain no organisms (ie, culture-negative endocarditis). These patients may have elevated erythrocyte sedimentation rate, anemia, thrombocytopenia, and hematuria. [30, 5]


Imaging Studies

Chest radiography may be required in patients with severe illness or pulmonary manifestations, especially in patients with RMSF and Q fever.

Other imaging studies may be necessary, depending on the severity of organ involvement and development of complications.



A Lumbar Puncture and other procedures may be needed to exclude other possible etiologies.


Histologic Findings

Evidence of vasculitis, angiitis, and perivascular mononuclear cell infiltration may be evident in involved organs.

Chronic Q fever infection of the skeletal system causes the formation of granulomatous lesions.