Key points
- Never delay or withhold treatment pending the receipt of laboratory test results, or on the basis of an initially negative result.
- Early recognition and treatment with doxycycline is critical to prevent severe illness.
- Always take a thorough patient history, including recent tick bites, exposure to areas where ticks or mites are found, and travel history.
Recommended tests
Rickettsial Disease Diagnostic Testing and Interpretation for Healthcare Providers
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Serology
Serologic assays are the most frequently used methods for confirming cases of spotted fever rickettsiosis (spotted fever). The reference standard for serologic diagnosis is the IFA test. Diagnosis is typically confirmed by documenting a four-fold or greater rise in antibody titer between acute and convalescent-phase serum samples. Acute-phase specimens are taken during the first week of illness and convalescent-phase samples are generally obtained 2–10 weeks after the resolution of illness. Eighty-five percent of patients will not have detectable antibody titers during the first week of illness and a negative test during this time does not rule out spotted fever infection. In most patients with a spotted fever group rickettsiosis, the first immunoglobulin G (IgG) IFA titer is negative and the second typically shows a four-fold or greater increase in IgG antibody levels.
Immunoglobulin M (IgM) antibodies are less specific than IgG antibodies and more likely to produce a falsely positive result. Closely related species of spotted fever group Rickettsia (SFGR) (such as R. rickettsii, R. akari, R. parkeri, or R. rickettsii subsp. californica) share similar antigens such that antibodies directed to one of these antigens can cross-react with other heterologous spotted fever group antigens. Commercial labs are unable to differentiate one spotted fever infection from another using these serologic methods.
Persistent Antibodies
Antibody titers can remain elevated for months or longer after the disease has resolved or can be detected in persons who were exposed previously to antigenically related organisms. For these reasons, as many as 10% of persons in some areas of the United States can have elevated levels of antibodies that react with R. rickettsii or similar organisms. Therefore, a single antibody titer should not be used to document or exclude a diagnosis of a spotted fever group rickettsiosis. The most conclusive method is the evaluation paired serum samples, collected 2-10 weeks apart, which reveal a four-fold or greater rise in antibody titer.
PCR, IHC, and Culture
SFGR species infect the endothelial cells that line blood vessels and do not circulate in large numbers in the blood until the disease has progressed to a severe phase of infection. For this reason, whole blood specimens obtained during the first several days of illness are often negative when tested by PCR assays or culture. If the patient has a rash or eschar, PCR, or immunohistochemical (IHC) assays can be performed on a skin biopsy specimen. Eschars may alternatively be swabbed for the collection of infected exudate. Swabs of eschars are less invasive than skin biopsies, but do not allow for IHC testing or cell culture evaluation. See instructions for the collection of skin biopsy pdf icon[PDF – 1 page] and eschar swabs pdf icon[PDF – 2 pages]. PCR, culture, and IHC assays can also be applied to autopsy tissue specimens. SFGR species are obligate intracellular pathogens and cannot be propagated using routine blood culture methods. Culture of SFGR species is generally available only at specialized laboratories that perform cell culture and are equipped with the appropriate biosafety facilities.
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Diagnosis
Spotted fevers can be difficult to diagnose due to the non-specific signs and symptoms in early stages of illness. Signs and symptoms can vary from patient to patient and can resemble other more common diseases. Nonetheless, early consideration of rickettsial disease in the differential diagnosis and empiric treatment is crucial to prevent severe illness. Many diagnostic tests for spotted fevers, especially tests based on the detection of antibodies, will frequently appear negative in the first 7-10 days of illness and cannot be relied upon for initiation of antibiotic therapy.
Patient History
Information such as recent tick bites, exposure to tick habitats, contact with dogs, similar illnesses in family members or pets, or history of recent travel to areas of high incidence can be helpful in making the diagnosis. Many people with rickettsial disease do not remember being bitten by a tick.
Other Clinical Evidence
Clinical indicators such as thrombocytopenia (low platelet count), hyponatremia (low serum sodium), or mild to moderately elevated levels of hepatic transaminases can be helpful predictors of spotted fever infection but may not be present in all patients, particularly those in early stages of illness. After a diagnosis is made on clinical suspicion and treatment has begun, specialized laboratory testing should be used to confirm the diagnosis.