Q.1: What
are the 3 basic tests that can be ordered if couple can afford to remove
apprehension about Treponemal infections?? Ans:--There are three basic methods
used in screening for syphilis. These include A) direct observation of the spirochete by dark field
microscopy, and B) nontreponemal and treponemal serologic antibody studies.
Pont 2: Q. What are
the limitations & utility of VDRL test ? Ans: As most of us
still remember that the abbreviation VDRL implies:” Ans: The venereal disease research laboratory (VDRL) test”. This tests is used to detect if a person has been infected with the bacteria causing syphilis, which is a sexually
transmitted disease. The test detects
the presence of antibodies against the bacteria Treponema pallidum. )
Point 3:- Q.3: What is the main limitations of VDRL tests?? Ans-VDRL test is used
for initial screening, & more sensitive nontreponemal tests such as the
rapid plasma reagin (RPR) . Whereas specific treponemal tests such as the
fluorescent treponemal antibody absorption (FTA-ABS) are used to confirm the
diagnosis. The importance of these screening tools is shown by past clinical
studies that have demonstrated 78% accuracy for the clinical diagnosis of
primary syphilis by experienced clinicians.
Point 4: There are basically two confirmagtory teats a) Having admitted that observing spirochete
in dark ground illumination is direct test and also b)
The second confirmatory is FTA-ABS test which should be performed if VDRL
or RPR is positive . But what are the indirect (inconclusive ) tests ?? How useful are
serological tets for treponemal?? Can second kind of tes be fasle positive ?? What is called Biological Flase Positive Recations??
Ans:_Serologic tests provide only indirect evidence of syphilis and may
be reactive in the absence of clinical, historical, or epidemiologic evidence
of syphilis. The reactivity in such cases is usually in low dilutions
(<1:8), however, in exceptional cases false reactivity in very high titers
(up to 1:256) has been reported; therefore, quantitative titer cannot be used
to differentiate between a false-positive reaction and syphilis. This is
especially true for persons who are IV drug users, where more than 10% have
false positivity with titers >8. False-positive reactions can also occur
with treponemal tests, but this is less common than with nontreponemal tests
Therefore, careful clinical interpretation of test results and other evidence
is necessary for proper diagnosis. Besides being BFP reaction, another factor
needed to be look into is reliability of technique and the quality of the
laboratory where it is done, because incidence of positivity increases due to
faulty procedure or wrong interpretation. BFP reaction is for inherent reasons
and not due to any technical error. BFP reactions comprise a high proportion of
all VDRL reactors. Therefore, the use of the VDRL as a screening procedure is
challenged. Therefore, before giving any conclusive opinion in regards to VDRL
reactivity, we need to take a proper history regarding any chronic illness such
as, systemic lupus erythematosus, rheumatoid arthritis or any autoimmune or
collagen disease, antiphospholipid syndrome, d
Point 4 :-Q. What are the limitations of Rapid plasma reagin (RPR) and
the VDRL tests?? Ans:- are used for initial screening These two are nonspecific
test but it is useful in follow up Tr ,
since the antibody titer declines on successful therapy. Dear members pl do remember
these are A) Nontreponemal tests and such tests are rapid, simple, and
inexpensive. They are the only tests which is principally recommended to
monitor the course of disease during and after treatment. B) such nontreponemal
tests can also serve to detect reinfection. The main limitations of
nontreponemal tests are their reduced sensitivity in primary syphilis and late
latent syphilis, false-positive results due to cross reactivity, and the
potential for false-negative results due to prozone phenomenon. Unfortunately,
no current laboratory test can distinguish one trepanomatosis from another, and
this must be considered in serology in areas of the world where yaws, pinta on
endemic trepanomatosis exist.
Point 5 : What tests used to be done in good old days ?? -Since very long time Venereal Disease Research Laboratory
(VDRL) test was to be performed solely by physicians to screen patients for
syphilis, yet VDRL is still the most commonly used test all over the world for
screening and it still remains unchallenged Unfortunately in this test, the
antibody detects antigens, which are nonspecific, thereby yielding much
false-positive reaction …The basis
of the VDRL test is that body produces antibody when infected, and in this VDRL
test the antibody is detected by subjecting the serum to an antigen, which is
composed of colorless alcoholic solution of beef cardiolipin, cholesterol, and
lecithin. It is a qualitative test for screening of syphilis, and currently all
nontreponemal tests are flocculation tests and both VDRL and RPR tests are modifications
of original Wasserman reaction.
Point 6:-Nontreponemal
screening tests have a sensitivity of 70–90% in primary syphilis. st should be repeated and a treponemal test
should also be performed.
All
serological tests are reactive in the early latency; however, the reactivity of
the nontreponemal tests decreases with the increasing duration of latency, and
in approximately 30% patients with late latent or late syphilis VDRL/RPR teIt needs to be confirmed by a treponemal test. All
serological tests are positive at secondary stage and sensitivity for all tests
including VDRL test which is approximately 100%; however, in 1–2% of patients’
false-negative nontreponemal tests can occur due to prozone phenomenon. A
presumptive diagnosis is based on the presence of typical rash and reactive
non-treponemal tests in a titer ≥1:8 in a patient with no previous history of
syphilis. If history of syphilis is present, then the criteria should be a
fourfold rise in titer. When a titer of nontreponemal test <1:8, the test
are negative. In all patients with late latent syphilis, lumbar puncture is
recommended to exclude neurosyphilis.In low prevalence populations,
false-positive results are common with both treponemal and nontreponemal tests.
Q.7: Dr Pal, How can we confirm congenital
syphilis ?? The diagnosis of congenital syphilis is complicated by the
trans-placental transfer of maternal nontreponemal and treponemal IgG
antibodies to the fetus. This
transfer of antibodies makes the interpretation of reactive serologic tests for
syphilis in infants difficult. Treatment decisions frequently must be made on
the basis of (1) identification of syphilis in the mother; (2) adequacy of
maternal treatment; (3) presence of clinical, laboratory, or radiographic
evidence of syphilis in the infant; and (4) comparison of maternal (at
delivery) and infant nontreponemal serologic titers using the same test and
preferably the same laboratory. Venous blood from both the mother and the child
should be tested. Asymptomatic congenital syphilis requires a comprehensive
approach. All infants born to mothers who have reactive nontreponemal and
treponemal test results should be evaluated with a quantitative nontreponemal
serologic test (RPR or VDRL) performed on infant serum because umbilical cord
blood can become contaminated with maternal blood and could yield a
false-positive result and should be examined thoroughly for evidence of
congenital syphilis (e.g., nonimmune hydrops, jaundice, hepatosplenomegaly,
rhinitis, skin rash, and/or pseudo paralysis of an extremity). Conducting a
treponemal test (i.e., TP-PA or FTA-ABS) on a newborn's serum is not necessary.
Point 8:-What is called as “biological
false-positive (BFP) VDRL test” ?? Ans;-This is only an indirect evidence of syphilis - The prevalence of BFP is generally
1–2%. Serologic tests provide only indirect evidence of syphilis and may be
reactive in the absence of clinical, historical, or epidemiologic evidence of
syphilis. The VDRL usually becomes reactive within the first few weeks after
infection, peaks during the first year, and then slowly declines, so that low
titers (levels) are seen in late syphilis.
Q. 9:-Dr Pal , can U
briefly mention the relevance of VDRL(screening
tets ) in cases of HIV infected mother ?? Relation of HIV and VDRL Test
The
interaction between syphilis and HIV infection is complex and remains incompletely
understood, despite there being more than two decades of clinical experience
with co-infected patients.
Serologic
tests for syphilis are the cornerstone of diagnosing untreated syphilis
infection, independent of HIV status. Nontreponemal assays, such as the RPR
card or VDRL test, use cardiolipin-, lecithin-, and cholesterol-containing
antigen to measure antilipoidal antibodies and are often used initially to
diagnose syphilis. The sensitivity of nontreponemal and treponemal tests for
syphilis increases with duration of infection, and ranges from approximately
75% in the primary stage to virtually 100% in the secondary stage. Because the
sensitivity of nontreponemal tests is lower that that of treponemal tests in
the primary stage, a negative nontreponemal test in an HIV-infected individual
with a genital lesion cannot exclude primary syphilis. It may be useful to
consider both a nontreponemal and a (nonreflexed) treponemal test as a
diagnostic strategy in newly infected persons with suspicious lesions. Unusual
serologic responses have been reported in HIV-infected persons with syphilis.
Most reports involved higher than expected serologic titers, but false-negative
serologic results and delayed appearance of sero-reactivity have also been
reported, albeit rarely. Nevertheless, serologic tests appear to be accurate
and reliable for the diagnosis of syphilis and the evaluation of treatment
response in most HIV-infected patients. The clinician should seek confirmatory
evidence for the diagnosis from any available source, including the patient's
history, clinical findings, direct examination of lesion material for
spirochetes, and serologic tests for syphilis. Reports of nontreponemal
antibody test results should be quantitative and describe the lowest dilution
(i.e., the titer) at which the test result is reactive. In general,
nontreponemal test titers may be higher among HIV-positive patients than among
HIV-negative persons.
Q. 11. What will
be threatment& follow up?? VDRL and Treatment Follow-up
There
is no ideal test of cure of syphilis available that can be carried out within
days or weeks after treatment to determine the status of a patient. Patients
should have serological tests for syphilis done on the day treatment is
initiated. To access it, the patient is asked to repeat quantitative
nontreponemal serological testing like VDRL/RPR and clinical evaluation at 3,
6, and 12 months. When serological test is negative, patient is assured to be
cured. Generally, seropositivity is achieved in majority of the patients with
primary syphilis in about 12 months after the treatment and in those with secondary
syphilis in about 24 months. Seroconversion is more rapid after therapy if
duration of infection is short and initial titer is low. As seroconversion is a
slow process requiring months to years, the rate of decline is a better
indicator of therapeutic response. A 4-fold decrease in titer is considered as
good response, and this should occur within 3-6 months after therapy in
patients with primary and secondary syphilis and within 12 months in patients
with early latent syphilis. The VDRL titer may not decrease in patients with
late syphilis and remains reactive at a low level (<1:8) for many years
after adequate treatment. There is no satisfactory monitoring test available
for nontreponemal test-negative late disease.
Nontreponemal tests are then monitored at a 6-month interval in patients
with latent disease without neurosyphilis to document a fourfold
decrease/seronegativity within 24 months after treatment. Low titers will
persist in approximately 50% of patients with late syphilis after adequate
therapy after 2 years. This low titer persistent seropositivity does not
signify treatment failure or reinfection, and these patients are likely to
remain serofast even if they are retreated. The FTA-abs (DS) is not recommended
for treatment follow-up. Nonreactive serologic tests and normal clinical
evaluation cannot exclude incubating syphilis.
In patients with neurosyphilis VDRL-CSF
is repeated at 4- to 6-month interval, if CSF pleocytosis or CSF-VDRL titers
are noted initially. Some experts recommend
that HIV-infected patients be followed more closely at 3-month interval.
The
literature VDRL reactor values for treated late latent syphilis and treated
late manifest syphilis are 1% only..Although higher values may have been
reported, they were unaccompanied by a specification as to the interval lapsed
between the times of treatment and testing.. Moreover, not even untreated
latent syphilis or late syphilis exceeds the VDRL reactivity of 70% (30% of the
diseased spontaneously become negative).
The
criteria for treatment failure currently include the following findings:
Persistence,
recurrence, or development of clinical signs or symptoms of syphilis in the
absence of reinfection.
Sustained
(greater than 2 weeks) fourfold (two dilutions) increase in the nontreponemal
test titer (assuming the same test type was used [e.g., VDRL, RPR].
Failure
of the initial nontreponemal test titer to decrease fourfold (two dilutions) by
6–12 months for primary, secondary, or early latent syphilis and by 12–24
months for late latent syphilis or syphilis of unknown duration
Point 12: Take home message: Practice Guidelines :--The diagnosis of
infection is commonly performed using the VDRL and TPHA tests. This is a
nonspecific test but it is useful in following treatment, since the antibody
titer declines on successful therapy. It also impresses on nonvenereologists
the need to cautiously order and interpret serological tests for the
demonstration of syphilis. This subsumes quantifying the VDRL among the
infected, and the use of modern tests to determine the intensity of syphilitic
process. In general, the sensitivity of treponemal tests continues to
approximate 100% in late syphilis, in contrast to nontreponemal tests, which
are more practical and cost-effective for initial screening but have diminished
sensitivity in late syphilis. Despite the higher sensitivity of treponemal
tests, they have not been recommended for initial screening in the many
countries, primarily because of cost.
It is
always advisable to interpret properly before giving any diagnosis to avoid any
legal complications in future, so also for the psychological well-being of the
patient. In accord with all diagnostic methods, a
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