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Comparison of the microhemagglutination assay for antibodies to Treponema pallidum and the automated fluorescent treponemal antibody-absorption test.

The qualitative microhemagglutination assay for detection of antibodies to Treponema pallidum and the automated fluorescent treponemal antibody-absorption tests were directly compared as confirmatory tests for syphilis. They were compared on 2,790 specimens from patients of New York City Social Hygiene Clinics. Overall agreement between the two assay methods was 89.6%. Only 1.5% of the total specimens tested were reactive by the automated fluorescent treponemal antibody-absorption test, and nonreactive by the microhemagglutination assay. The majority of specimens which disagreed were reactive only by the microhemagglutination assay. These comprised 8.9% of the total specimens tested. When such specimens were further tested by the manual fluorescent treponemal antibody-absorption test, 63% were also reactive in that test, and 16.7% gave borderline reactions. Fifty-four per cent of those reactive specimens were from patients suspected of being in a latent stage of syphilis, 10% from patients suspected of being in other stages, and 36% from patients not suspected of having syphilis. Because of the increased sensitivity of the microhemagglutination assay, its use is recommended instead of the automated fluorescent test. However, the manual fluorescent test should be performed when the result of the microhemagglutination assay is completely inconsistent with the clinician's impression.

Antibodies, Bacterial↗

Immunoglobulin specificity for the fluorescent treponemal antibody-absorption test conjugate.

Quantitative indirect immunofluorescence tests have demonstrated the predominance of immunoglobulin G antibody in most stages of syphilis. A class-specific anti-human immunoglobulin G conjugate is recommended to replace the present fluorescent treponemal antibody-absorption test conjugate. This would allow further definition and standardization of the fluorescent treponemal antibody-absorption test.

Antibody Specificity↗

Problems affecting performance of the fluorescent treponemal antibody-absorption test for syphilis.

Immunofluorescent staining of Treponema pallidum was studied to clarify the effect of three factors on the results of the fluorescent treponemal antibody-absorption test: (i) heat inactivation of sera at 56 degrees C for 30 min before testing, (ii) use of multicircle slides, and (iii) tungsten illumination to visualize and assess unstained treponemes on reactive as well as nonreactive smears. It was found that serum inactivation before testing was not necessary for detection of immunoglobin G antibody, but an immunoglobulin M prozone was detected in unheated serum. On multicircle slides, it was demonstrated that a false-positive reaction could be obtained in 30 s at 37 and 25 degrees C if a smear where a nonreactive serum had been placed was crossed by a strongly reactive serum from another circle. Tungsten illumination proved necessary for correct assessment of unstained treponemes on all fluorescent treponemal antibody-aborption test smears, reactive or nonreactive. The possible role of these factors in incorrect fluorescent treponemal antibody-absorption test results is discussed.

Antibodies, Bacterial↗

Genital herpes and the FTA-ABS.

The fluorescent treponemal antibody-absorption test (FTA-ABS) was obtained on a series of 55 healthy men and women with documented recurrent genital herpes. In contrast to a previous report indicating that a significant number of these patients demonstrated a false positive FTA-ABS, the present series failed to confirm these findings. Of interest, however, was the high incidence of borderline FTA-ABS tests seen in both the control group and the group with herpes. The significance and use of the FTA-ABS are briefly discussed.

False Positive Reactions↗

[Value of TPHA in the serological screening of lues].

In the present work, 21,400 not selected sera were tested with hemagglutination test (TPHA) and flocculation test (VDRL) with cardiolipin for screening of syphilis; sera that gave negative results against both tests showed remarkable agreement (97,81%). 468 sera gave positive results to least one of the tests employed in screening and were tested with the following procedures: fluorescent Treponemal antibody-absorption (FTA/ABS) test, complement fixation (by Kolmer, modified) with proteic (KP) and lipidic (KL) antigen; 100 of these sera were also tested with T. pallidum immobilizaiton (TPI) test. The agreement among the before mentioned tests and sera that gave positive results only to VDRL was significatively low; on the contrary, the agreement was remarkable in the case of those positive only to TPHA (99% with FTA/ABS, 83% with TPI, 52,5% with KP and 21,5% with KL). The results obtained in attesting sensitivity and specificity of TPHA indicate that it is a very valuable screening test, and suggest to the AA. to emphasize that TPHA/VDRL association a definitive conclusion in syphilis serological negativity.

Antibody Formation↗

The fluorescent treponemal antibody-absorption (FTA-ABS) test for syphilis.

The FTA test was developed at a time when immunofluorescence procedures were not well-defined. Through technique control and research, a modification of the FTA test, the FTA-ABS, has attained a position as one of the leading treponemal tests to confirm the reagin tests for syphilis. In this review of the FTA-ABS test, attention has been focused on reagent development, with the anticipation that reagent standardization may soon become a reality. The T. pallidum antigen obtained by extracting infected rabbit testicular tissue has evolved from a preparation in which the treponemes remained in the initial extracting fluid to a reagent that can be free of rabbit tissue and globulin. These washed antigen preparations improve visibility of the treponemes on the microscope slide, reduce background fluorescence, and reduce or prevent from occurring nonspecific reactions that are a result of tissue and globulin components. Both washed and nonwashed antigens are available commercially, and, to date, little differentiation has appeared on the product label. The predominant immunoglobulin that reacts with T. pallidum in the indirect fluorescent antibody tests appears to be IgG. This is the major immunoglobulin detected in the FTA-ABS test. IgM, although increased in early syphilis, is also increased in other clinical conditions. Several reports suggest that adult IgM detection in the present FTA-ABS test would be nonspecific. Until specific IgM antibody in adult syphilis can be detected without a risk to test specificity, the conjugate for the FTA-ABS test should continue to be an anti-IgG reagent. Class-specific, anti-IgG reagents are more expensive than other reagents; however, their use may eliminate the problem of nonspecificity resulting from IgM detection. Additionally, micromethods can be used to reduce cost, and this possibility should be investigated. The sorbent that contains an antigen to the Reiter treponeme may or may not specifically absorb the reactivity that occurs in normal sera; certainly, there are questionable aspects about this reagent. Group antibodies not related to Reiter treponemes may be responsible for some nonspecific reactivity; additionally, antiglobulin factors have been reported to participate in the reaction. Antigens free of rabbit serum factors and class-specific, antiimmunoglobulin reagents are available, and may lead to a better understanding of nonspecific reactions. These reagents should allow resolution of the possible multiplicity of reactivity. In this interim period, the sorbent, with its possible nonspecific nature, appears to maintain a biological balance between natural or group and immune antibodies when used to detect IgG antibody.

Absorption↗

Serologic diagnosis of syphilis: an update.

Tests used in the serologic diagnosis of syphilis can be divided into two main groups: nontreponemal (reagin) tests and treponemal tests. The most widely used nontreponemal test is the Venereal Disease Research Laboratory (VDRL) slide test, and the standard treponemal test is the manual fluorescent treponemal antibody-absorption (FTA-ABS) test. These tests and other newer tests available for the serologic diagnosis of syphilis are reviewed, with emphasis placed on their current clinical usefulness.

Complement Fixation Tests↗

Luetic endolymphatic hydrops: diagnosis and treatment.

Luetic endolymphatic hydrops (LEH) is an effectively treatable disorder that requires astute clinical judgment to suspect, confirm, and treat. We provide a review of the literature as well as recommendations regarding the clinical management of LEH with discussion of several illustrative cases. We also give an overview of laboratory testing for the diagnosis and monitoring of the infectious process. Ultimately, the control of the otologic symptoms in LEH requires acumen on the part of the clinician.

Aged↗

Otosyphilis: a diagnostic and therapeutic dilemma.

Traditional treatment of otosyphilis with penicillin and corticosteroids has achieved hearing improvement; however, selecting which patients with a positive fluorescent treponemal antibody absorption (FTA-ABS) test will benefit from treatment remains a problem. In order to study this problem, 18 patients with cochleovestibular dysfunction of unknown etiology and positive syphilis serology were treated with intravenous penicillin and corticosteroids. In addition, lumbar puncture and human immunodeficiency virus (HIV) testing were performed on all patients. Hearing improved in 5 (31%) of 16 patients, tinnitus decreased in 11 (85%) of 13, and vertigo improved in 6 (86%) of 7. Factors associated with hearing improvement were hearing loss present less than 5 years, fluctuating hearing, and age less than 60. Improvement was unrelated to the severity of the loss or previous therapy. All patients with cerebrospinal fluid abnormalities, including two patients with HIV disease, had subjective improvements. A diagnostic and treatment protocol is presented.

Adult↗

Serological tests in cerebrospinal fluid for congenital syphilis in central Africa.

Serological tests were performed in the cerebrospinal fluid (CSF) of 13 children with active congenital syphilis (presence of specific IgM FTA-ABS antibodies) and of seven seropositive children with no active syphilis (FTA-ABS IgM-negative) born to syphilitic treated mothers in Libreville, Gabon. Antibodies against treponema were measured by the Venereal Disease Research Laboratory test (VDRL), the Treponema pallidum haemagglutination assay (TPHA) and the fluorescent treponema antibody absorption tests (FTA-ABS IgG and IgM). Of the 13 children with active syphilis, seven had a positive FTA-ABS IgG in the CSF. The result of this test was not correlated with the severity of clinical features, CSF protein levels or number of CSF white blood cells. The CSF-TPHA test was positive in four out of 12 children, and the CSF-VDRL test was negative in all the children with active congenital syphilis. One of the seven newborns with mother-transmitted antibodies had a positive FTA-ABS and TPHA in the CSF. These data show that the VDRL is not sensitive enough to diagnose congenital neurosyphilis, and that FTA-ABS or, at least, TPHA are convenient, sometimes with false-positive results, when a sophisticated method of detecting specific IgM in CSF is not available.

Fluorescent Treponemal Antibody-Absorption Test↗

Depressed CD4/CD8 ratio in TPHA-negative patients with syphilis.

The Treponema pallidum hemagglutination assay (TPHA) is a widely used method for screening syphilis. We report our experience with six elderly (age 72.4 +/- 8.3 years) patients with syphilis, whose TPHA was negative. Their cardiolipin (RPR) and absorbed fluorescence treponemal tests (FTA-ABS) were positive. TPHA-negative patients with syphilis were compared with TPHA-positive syphilitics by immunological analysis. We found that both the numbers and the percentage of CD4 cells in TPHA-negative syphilitics were significantly lower than those in TPHA-positive syphilitics (722 +/- 142 vs. 1,064 +/- 141/mm3, P less than 0.01: 35.1 +/- 6.9 vs. 48.4 +/- 6.4%, P less than 0.01) and that the ratio of CD4 to CD8 was also lower in TPHA-negative syphilitics compared with TPHA-positive syphilitics (1.08 +/- 0.46 vs. 2.24 +/- 1.07, P less than 0.05). These data suggest that the TPHA is insufficient for excluding elderly syphilitics because of immunological impairment seen in aged patients.

Adult↗

Rapid detection of specific treponemal antibodies by counterimmunoelectrophoresis using an extract of Treponema pallidum.

Specific treponemal antibodies were detected in small amounts by counterimmunoelectrophoresis (CIE) in agar gel, using an extract of Treponema pallidum. The T. pallidum-CIE test was compared with the fluorescent treponemal antibody-absorption (FTA-ABS) test and with the Reiter protein complement fixation (RPCF) test. The results of the T. pallidum-CIE and FTA-ABS tests agreed in 96% of cases. There was no agreement between the T. pallidum-CIE and RPCF tests in 14% of cases. The three tests were compared in 56 sera--17 from cases of untreated syphilis and 39 from biologically false positive (BFP) reactors. RPCF was positive in 10 (59%) of the 17 specimens from cases of untreated syphilis; all 17 sera were FTA-ABS positive. The T. pallidum-CIE test was positive in 14 (82%) of the 17 specimens. All of the 39 BFP reactors, positive by the RPCF test, were shown to be negative by the FTA-ABS and T. pallidum-CIE tests. These results suggest that the T. pallidum-CIE test is more specific than the RPCF test and slightly less specific than the FTA-ABS test. The advantages of the T. pallidum-CIE test as a convenient method are speed of performance, simplicity and economy.

Antibodies, Bacterial↗

Hemagglutination tests for syphilis antibody.

In a study of serodiagnosis of syphilis, the authors compared the specificities and sensitivities of two hemagglutination tests, a sheep-erythrocyte test (MHA-TP) and a trukey-erythrocyte test (TPHA), with those of the Fluorescent Treponemal Antibody-Absorption (FTA-ABS) test. In tests of sera from 935 patients without syphilis, the MHA-TP, TPHA, and FTA-ABS tests were reactive for 0.96, 0, and 1.3% respectively. The false-positive results were usually transient and not associated with underlying illness. For the 68 patients with syphilis, the MHA-TP test was as sensitive as the FTA-ABS test in all stages except untreated primary disease. The TPHA test appeared to be undersensitive, and testing of follow-up sera from persons with latent syphilis showed unexplained conversion of false-negative TPHA results to reactive results. Reproducibilities of the two hemagglutination tests were comparable. The MHA-TP test is a valuable confirmatory test for syphilis. Further study is needed before the use of the TPHA test can be recommended.

Animals↗

[A case of early syphilis presenting general paresis-like symptoms and bilateral tonic pupils].

A 40-year-old man was admitted after 8 months of speech disturbance and locomotive ataxia. He had no seizures, lightning pains, paresthesia, visual loss, bladder disturbance or rectal incontinence. He had never been neurologically or psychiatrically ill and had no history of syphilis. When the patient was admitted, his general physical examination including blood pressure and dermatologic examination was normal. His consciousness was alert. He was found to have a deterioration of mental status such as inability to concentrate, failing memory, amnesia and circumstantiality. His pupils were anisocoric and Achilles jerks were absent. No rigidity of the neck muscles, paralysis and sensory disturbance were recognized. Romberg's sign was absent. The right pupil was 7.0 mm and the left was 6.0 mm in room illumination. The pupils were nonreactive to bright light and both did not constricted to near stimuli. 0.125% pilocarpine eyedrops produced bilateral pupillary constriction. The results indicated bilateral tonic pupils. Laboratory data revealed white cell count of 12,600/mm3 and normal erythrocyte sedimentation rate of 8 mm/hr. Cerebrospinal fluid (CSF) examination revealed the following: opening pressure, 140 mm of water; cell counts, 76/mm2 (mononuclear cells); total protein, 116 mg/dl; glucose, 57 mg/dl. A serum venereal disease research laboratories (VDRL) test was positive in a 1:32 titer confirmed by positive treponema pallidum hemagglutination (TPHA) test in a 1:40,960 titer and positive fluorescent treponemal antibody-absorption (FTA-ABS) test. Serum TPHA-IgM was positive in a 1:320 titer but TPHA-IgG was negative. CSF examination revealed positive TPHA test (titer of 1:2,560) and positive FTA-ABS test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The laboratory diagnosis of syphilis. New concepts.

Although new tests for syphilis, as well as new applications of standard tests, continue to appear, the usefulness of several of these procedures has not been determined. When the Fluorescent Treponemal Antibody-Absorption (FTA-ABS) test is used to screen for syphilis, the proportion of positive results that are true positives decreases. The value of modified FTA tests in the diagnosis of neurosyphilis and congenital syphilis remains unproved. Although not studied as extensively as the standard tests, several newer methods--the direct fluorescent antibody test for Treponema pallidum (DFATP), the Rapid Plasma Reagin (RPR) card test, and the microhemagglutination test for T. pallidum (MHA-TP)--may have certain advantages. To be of optimal diagnostic value, tests for syphilis must be selected according to the clinical situation.

Cerebrospinal Fluid↗

Evaluation of reagin card tests for syphilis.

The macroscopic rapid plasma reagin (RPR) and reagin screen (RST) card tests for syphilis were compared. Test specimens were also examined with the Venereal Disease Research Laboratory (VDRL) microscopic slide test; those reactive in the card or slide tests were examined with the fluorescent treponemal antibody-absorption (FTA-ABS) procedure. Agreement between the card tests with 2,300 specimens was 99%; among all three reagin tests it was 96.3%. With 348 specimens reactive in one or more of the tests, there was 75.6% agreement among all three tests. The FTA-ABS was reactive with 71% of the RPR- or RST- and 65% of the VDRL-reactive specimens. The comparison showed that the card tests give results in close agreement with those of VDRL while offering a number of practical advantages over it.

Adult↗

Evaluation of reagin screen, a new serological test for syphilis.

A total of 1,020 serum and plasma specimens were tested using the Venereal Disease Research Laboratory (VDRL), Rapid Plasma Reagin (RPR) card, Reagin Screen (RST) and Fluorescent Treponemal Antibody-Absorption (FTA-ABS) tests. In 257 normal patients, all screening tests were nonreactive; the FTA-ABS test was reactive for one patient. In 588 patients with treated and untreated syphilis, the RST results were 91.7% in agreement with the VDRL and RPR results. In 175 patients with diseases that cause biological false reactions, the RST was 94% in agreement with the other screening tests. The titer of the RST was within one dilution of the corresponding VDRL titer in 91.7% of the 360 speciments tested and within one dilution of the RPR titer in 96.9% of 358 specimens quantitated by both tests.

Antibodies↗

Destructive bone disease in early syphilis.

Although destructive bone disease is a well-known complication of tertiary syphilis, osteitis or osteomyelitis are not commonly recognized as complications of early (primary or secondary) syphillis. A patient with secondary syphilis characterized by generalized lymphadenopathy, perianal condyloma lata, and positive rapid plasma reagin (RPR) and fluorescent treponemal antibody-absorption (FTA-ABS) tests also complained of headache, right should pain, and right anterior chest pain and swelling. Roentgenograms showed mottled osteolytic lesions consistent with previously described luetic bone disease. Biopsy confirmed the diagnosis of syphilitic osteomyelitis, and treatment with penicillin resulted in prompt resolution of symptoms.

Adult↗