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Diagnostic Methods (continued)
Serologic Tests for Syphilis
In the absence of darkfield microscopy or a DFA-TP, a presumptive diagnosis of syphilis is possible with the use of two types of serologic tests: nontreponemal and treponemal. The use of
only one type of serologic test is insufficient for diagnosis because
false-positive nontreponemal test results may occur secondary to various medical conditions.
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Nontreponemal tests
Nontreponemal tests include VDRL (Venereal Disease Research Laboratory), RPR (Rapid Plasma Reagin), TRUST (Toluidine Red Unheated Serum Test), and USR (Unheated Serum Reagin). These tests measure IgM and IgG antibody and are not specific for T. pallidum.
Nontreponemal test titers usually correlate with disease activity, and
the results are reported quantitatively. A fourfold change in titer, equivalent to a change of two dilutions (e.g., from 1:16 to 1:4 or from 1:8 to 1:32) is considered necessary to demonstrate a clinically significant difference. Sequential serologic tests in individual patients should be performed by using the same testing method (e.g., VDRL or RPR), preferably by the same laboratory.
The VDRL and RPR are equally valid assays, but quantitative results from the two tests
cannot be compared directly because RPR titers are often slightly higher than VDRL titers. TRUST
is similar to RPR and USR is similar to VDRL.
Nontreponemal tests usually become nonreactive with time after treatment. In some patients, however, nontreponemal antibodies can persist at a low titer for a long period of time, sometimes for the life of the patient. This response is referred to as the "serofast reaction."
Some clinical laboratories and blood banks have begun to
screen samples using treponemal EIA tests. This strategy
will identify both persons with previous treatment and
persons with untreated or incompletely treated syphilis.
False-positive results can occur, particularly among
populations with a low prevalence of syphilis.
Persons with a positive treponemal screening test should
have a standard nontreponemal test with titer to guide
patient management decisions. If the nontreponemal test is
negative, then a different treponemal test should be
performed to confirm the results of the initial test. If a
second trepomenal test is positive, treatment decisions
should be discussed in consultation with a specialist. Advantages of serologic nontreponemal tests:
- Rapid.
- Inexpensive.
- Can use plasma rather than serum (RPR, TRUST).
- Easy to perform.
- Can be done in clinic or office.
- Quantitative.
- Can be used to follow response to therapy and evaluate possible reinfection.
Disadvantages of serologic nontreponemal tests:
- May be insensitive in certain stages (particularly
early primary, late latent, and tertiary (late)).
- False-positive reactions can occur (see section on
false-positive reactions at
the bottom of this page).
- Rarely, a phenomenon called
the “prozone effect” may cause a
false-negative
reaction. The prozone effect occurs when the reaction is
overwhelmed by antibody excess. It is most likely to
occur in secondary syphilis. If clinical suspicion of
secondary syphilis is high, the lab should titer the
sample or dilute the serum to a 1/16 dilution and repeat
the qualitative test to rule out the prozone effect.
Treponemal tests
The treponemal tests include TP-PA (T. pallidum particle agglutination), FTA-ABS (fluorescent treponemal antibody absorbed),
and EIA (enzyme immunoassay). These tests measure antibody directed against T. pallidum antigens by particle agglutination (TP-PA), immunofluorescence (FTA-ABS),
or enzyme reaction (EIA).
These qualitative tests are most often reactive for life, even after adequate treatment. However, 15%-25% of patients treated during the primary stage revert to being serologically nonreactive after 2-3 years. Treponemal antibody titers correlate poorly with disease activity, and they should not be used to assess treatment response.
The following chart compares the sensitivity of various serological tests by stage of syphilis.
(Click on image for larger view)
False-positive reactions
False-positive reactions can occur with both nontreponemal
and treponemal serologic tests for syphilis. The following
slide lists causes of false-positive reactions for various
serologic tests. In addition to those listed on the
slide, technical
errors and transient unknown causes can lead to false-positive reactions in treponemal and nontreponemal tests.
(Click on image for larger view)
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