The nontreponemal tests can detect non-specific treponemal antibodies. There are two common tests under the nontreponemal test. They include VDRL (Venereal Disease Research Laboratory) and RPR (Rapid Plasma Reagin). These two tests are performed in the same way. However, they have a few differences.
VDRL test
was developed by the Venereal Disease Research Laboratory during World
War I. This test is still done today to detect syphilis.
RPR was
developed as a more advanced VDRL. RPR is just the VDRL antigen, but it
contains carbon or delicately divided charcoal particles. With these charcoal
particles, it allows the visualization of the reaction or flocculation between
the specimen and the antigen without the use of a microscope.
RPR-VDRL (Serologic
Tests for Syphilis)
A variety of serologic tests for syphilis are available,
including:
1)
VDRL (Venereal Disease Research Laboratory)
2)
RPR (Rapid Plasma Reagin)
3)
FTA-ABS (Fluorescent Treponemal Antibody
Absorption)
4)
TP-MHA (Treponema Pallidum Microhemagglutination
Assay)
Each differs the others in the precise substance being
measured, complexity, and specificity. All are satisfactory for use in managing
syphilis. Abnormals may be:
Reactive, Weakly reactive, or Bordeline
Whenever a screening test (RPR, VDRL) is positive, a more
specific test (FTA-ABS, TP-MHA) should be used to confirm the test and rule out
a "biologic false positive."
A “negative”
or "nonreactive" test may indicate:
·
The patient doesn't have syphilis
·
The patient has syphilis, but is so early in the
course of the disease that the test has not yet turned positive. In these
cases, the test may never turn positive if the patient is effectively treated.
·
The patient had primary syphilis, had a positive
test, was effectively treated, 6 months have passed and the test has now
reverted to negative.
·
The patient had secondary syphilis, had a
positive test, was effectively treated, 12-18 months have passed and the test
has now reverted to negative.
·
The patient has syphilis, but his/her immune system
is impaired.
A “positive”
or "reactive" test may indicate:
·
The patient has syphilis.
·
The patient had syphilis, was effectively
treated, but the test has not yet returned to negative:
o
With primarily syphilis, it typically takes
about 6 months for the test to turn negative.
o
With secondary syphilis, it typically takes
12-18 months for the test to turn negative.
o
The longer syphilis remains untreated, the
longer it will take for the test to return to normal, and the less likely it is
to ever return to normal.
·
The patient has a biologic false positive (BFP)
The traditional screening algorithm pathway (see FIGURE 1) relies on the initial analysis of a NTT such as the RPR (rapid plasma reagin) or Venereal Disease Research Laboratory (VDRL) test. If the initial result is reactive, then additional testing is done to confirm the primary result. This additional testing can be done in several ways, including via TP-PA, fluorescent treponemal antibody absorption (FTA-ABS), enzyme immunoassay (EIA), or chemiluminescence immunoassay (CLIA). A reactive result on this confirmatory test is to be considered diagnostic of active T. pallidum infection. Additional specificity for T. pallidum diagnosis is achieved with IgG- and/or IgM-class antibodies detected with the NTT methods described above..
|
Traditional
Testing Algorithm |
||
|
Non-Treponemal Assay |
Treponemal Assay |
Interpretation |
|
Non-Reactive |
Not Indicated* |
No laboratory evidence of syphilis infection |
|
Reactive |
Non-Reactive |
Syphilis Infection unlikely; biological false
positive likely |
|
Reactive |
Reactive |
Current or past syphilis infection |
*If there is high clinical
suspicion for early acute disease, then serologic testing should
be repeated in 2-
4 weeks, or the patient should be presumptively treated.
The reverse algorithm (see FIGURE 2) is another
alternative used by health care providers. Recent studies have indicated that
reverse sequence screening may detect more cases of early or latent syphilis
than the traditional forward screening algorithm.6 As
recommended by the Centers for Disease Control and Prevention (CDC), discordant
syphilis IgG and RPR results are to be resolved by a second treponemal test
(TP-PA).7 In the presence of a positive syphilis IgG and
non-reactive RPR, a non-reactive treponemal test indicates a false positive
syphilis IgG screen because TP-PA has a higher sensitivity than syphilis IgG
screening.8 A treponemal confirmation test deemed positive
typically results in patient treatment, as the regimen is inexpensive and the
consequences of a missed public health opportunity can be large.
This reverse algorithm pathway is gaining traction among
obstetric health care providers due to the cross-reactivity of the RPR test
with medical conditions such as other infections (eg, HIV), pregnancy,
autoimmune disorders, injection-drug use, older age, or immunizations.
Screening out this approximately 1% of the population that exists as false
positive has become a necessity (see FIGURE 3). Aside from
the obvious benefits of lab automation, this method also represents less
intensive patient follow-up and stress from treatment. Although not as widely
preferred as the forward algorithm, CPL provides guidance to clinicians for
interpreting reverse algorithm results (see FIGURE 4). Both of
these approaches are summarized in FIGURE 5.
|
Reverse Testing Algorithm |
|||
|
Treponemal Assay |
Non-Treponemal Assay |
Treponemal Assay |
Interpretation |
|
Non-Reactive |
Not Indicated |
Not indicated |
No laboratory evidence of syphilis infection |
|
Reactive |
Non-Reactive |
Non-Reactive |
Inconclusive
for syphilis infection; potentially early infection or false positive. If recent exposure, recommend
re- screening in 2-4 weeks. |
|
Reactive |
Non-Reactive |
Reactive |
Past or potential early
syphilis infection |
|
Reactive |
Reactive |
Not indicated |
Current or past syphilis infection |
One significant potential limitation of using the reverse algorithm exclusively is the prevalence of the impact of false-positive results that can contribute to a burden of anxiety and treatment.9 However, other more obvious benefits of the reverse screening pathway include the ability to perform the treponemal IgG test on a high throughput analyzer (such as the Bio-Rad BioPlex 2200). Furthermore, the quantitative result obtained from this test aids in the monitoring of disease progression, especially during the tertiary phase. The reverse screening process studied by the University of Iowa Hospitals and Clinics has proven that 99% of results screened negative (1% screened positive).10 While the initial IgG treponemal test may be more expensive per test, overall client satisfaction is improved by providing results more rapidly.
