From the Guidelines
To rule out rickettsial infections, the most appropriate laboratory test is serologic testing with immunofluorescence assay (IFA), which is the gold standard, and it should be performed using paired serum samples collected during the acute and convalescent phases of illness to demonstrate a fourfold rise in antibody titers 1. The IFA assay is highly sensitive at detecting antibody 2–3 weeks after illness onset, and assay results are best interpreted if serum samples collected in the acute and convalescent phases of illness are tested in tandem 1.
- The sensitivity of IFA assays increases in tandem with pathogen-specific antibody production as the illness progresses past 7 days 1.
- A diagnosis of tickborne rickettsial disease is confirmed with a fourfold or greater increase in antibody titer in samples collected at appropriately timed intervals in patients with a clinically compatible acute illness 1.
- PCR testing can also be performed on whole blood, skin biopsies from rash sites, or eschar samples during the first week of illness before antibiotic treatment begins, especially for ehrlichioses and anaplasmosis 1.
- Additional supportive tests include complete blood count, comprehensive metabolic panel, and coagulation studies, which can help identify thrombocytopenia, leukopenia, mild anemia, elevated liver enzymes, and coagulation abnormalities.
- Empiric antibiotic therapy with doxycycline should not be delayed while awaiting test results if clinical suspicion is high, as rickettsial diseases can progress rapidly and become life-threatening 1. The timing of sample collection relative to symptom onset and whether antibiotics have been started can affect the sensitivity of these tests 1.
- It is essential to note that a single elevated antibody titer is never sufficient to confirm acute infection with a rickettsial pathogen, and serial titers are needed for confirmation 1.
- The reference standard for diagnosis of tickborne rickettsial diseases is the IFA assay using paired serum samples obtained soon after illness onset and 2–4 weeks later, with demonstration of at least a fourfold rise in antibody titer considered confirmatory evidence of acute infection 1.
From the Research
Lab Tests for Rickettsia
To rule out rickettsia, several lab tests can be employed, including:
- Serological tests, which remain an indispensable tool in the diagnosis of rickettsial diseases 2
- Microimmunofluorescence, considered the test of choice, followed by latex agglutination, indirect hemagglutination, immunoperoxidase assay, and enzyme-linked immunosorbent assay (ELISA) 2
- Immunoblot analysis, which can be used to confirm the results of other tests 2
- Polymerase chain reaction (PCR) technology, which can detect rickettsial DNA in acute phase blood specimens 3
- Indirect immunofluorescence assay, which is the test of choice for serology 4
Characteristics of Lab Tests
The characteristics of these lab tests include:
- Sensitivity and specificity, which vary among the different tests 3
- The need for specific diagnostic antigens to maximize the specificity of test results 3
- The use of enzyme-linked immunosorbent assays (ELISA), which are extremely sensitive but may lack specificity due to the general unavailability of specific diagnostic antigens 3
- The potential for molecular characterization of rickettsial antigens to produce peptide antigens that are specific for each species 3
Examples of Lab Tests
Examples of lab tests that can be used to rule out rickettsia include:
- The Weil-Felix test, although its use should be reserved for situations in which other serologic tests are not available due to its low specificity and sensitivity 2
- The ELISA method, which is expected to fulfill the highest requirements as to sensitivity in differentiation of rickettsioses within the known classification groups 5
- A newly developed ELISA for the serodiagnosis of Rickettsia parkeri infection, which shows greater sensitivity and resolution in observed titers than the IFA 6