SYPHILIS: Serology

doi:10.1016/S0733-8635(05)70034-6

Dermatologic Clinics

Volume 16, Issue 4, 1 October 1998, Pages 691-698

https://doi.org/10.1016/S0733-8635(05)70034-6 Get rights and content

Microbiologic tests are essential in making, or excluding, a diagnosis of syphilis, but it is mandatory that they are interpreted in relation to the patient history and physical examination. Treponema pallidum cannot be cultured in vitro, and apart from the very early stage of disease (when T. pallidum may be detected in the lesions of primary syphilis before an antibody response is detectable) serology is the mainstay of laboratory testing. A variety of screening tests are used, and it is important for the clinician to know if the testing strategy is best suited to detect or exclude only infectious syphilis, all stages of untreated syphilis, or a history of syphilis at any time in the past. Basically, syphilis serodiagnosis depends on the principle of dual-level testing, and, irrespective of which screening test is used, a positive reaction should always be confirmed by further testing. Once syphilis is confirmed, the clinician also looks to the laboratory to help assess treatment status; monitor the efficacy of treatment; and assist with special problems, such as the diagnosis of neurosyphilis and congenital infection. Not all laboratories need perform the full array of tests, and it is becoming increasingly common for sera reactive on screening to be referred to specialized regional or national reference centres for confirmatory and follow-up testing.

Immunoblotting studies have shown that infection with T. pallidum produces antibodies to more than 20 different polypeptide antigens. The number of antigens recognized by antibodies and the intensity of reactivity increase initially and reflect the duration of clinical symptoms. By the time clinical signs develop, most patients have both immunoglobulin G (IgG) and IgM antibody. Specific anti– T. pallidum IgM is detectable during the second week of infection, whereas production of IgG begins around the fourth week after infection and usually reaches much higher titres than those for IgM. The spectrum and intensity of reactivity decrease with duration of infection, even in the absence of treatment. Although IgM is undetectable in many cases of late syphilis, IgG reactivity usually persists. Therapeutic intervention causes a generalized loss of antibodies against individual antigens, but low levels of specific IgG usually remain detectable.

There are reports that HIV-infected patients who acquire syphilis may fail to produce antitreponemal antibodies. Although this has serious implications for the diagnosis and control of syphilis, some of the patients described as seronegative are more accurately classified as showing delayed seropositivity.⁴³ In most HIV-infected patients, the serologic response is either normal or exaggerated with very high antibody titres.³⁰

Section snippets

SEROLOGIC TESTS AND PATTERN OF REACTIVITY IN DIFFERENT STAGES OF SYPHILIS

The tests used to measure antibody responses in treponemal infection can be divided into two major categories: (1) tests to detect antibodies produced against nonspecific treponemal antigens, that is, the cardiolipin or lipoidal antigen tests, formerly termed “reagin” tests, such as VDRL, RPR; and (2) tests to detect antibodies specific for pathogenic treponemes, that is, the T. pallidum antigen tests, such as TPHA, EIA, and FTA-abs. Most of these tests use native antigen comprising relatively

SIGNIFICANCE OF DIFFERENT SCREENING STRATEGIES

In the United States, because the epidemiologic procedures are based on identifying active cases of syphilis, the RPR test is the recommended screening test in hospital laboratories, whereas screening with treponemal antigen tests is restricted to blood banks.¹⁹ The advantages and disadvantages of this strategy can be gleaned from the serologic patterns shown in Table 1. The main advantage is that the majority of adequately treated cases (unless recently treated) are negative: this means that

NEUROSYPHILIS

A diagnosis of neurosyphilis is based on abnormalities in the cerebrospinal fluid (CSF). Note that contamination of the CSF with even a small amount of blood can yield misleading results. The CSF need only be examined in patients with a positive treponemal antigen test result on blood. Indeed, neurosyphilis is extremely unlikely at serum TPHA titres below 640.⁸ A negative treponemal antigen test on blood has an extremely high predictive value for excluding neurosyphilis and is of course a

CONGENITAL SYPHILIS

Congenital infection is preventable through serologic testing as part of comprehensive prenatal care. Although congenital syphilis is rare in most of Europe, throughout the 1980s there was a steady increase in the number of cases of congenital syphilis in certain areas of the United States. The 1988 surveillance case definition encompassed any infant whose mother had untreated or inadequately treated syphilis at delivery and therefore included many noninfected infants.³² Confirmed cases were

Dark Ground Microscopy

Treponema pallidum can be demonstrated in primary and early secondary lesions by dark ground microscopy. Serum obtained from the depth of the lesion is examined immediately using the oil immersion objective. T. pallidum is recognized by its slender structure, characteristic slow movements, and angulation. Accurate interpretation of dark ground microscopy is dependent on a highly experienced observer—the decrease in primary syphilis means that experience in dark ground microscopy is limited. If

SUMMARY

Microbiologic tests are essential in the diagnosis and management of patients with syphilis. Apart from the very early stage of disease (when T. pallidum may be detected in the lesions of primary syphilis before an antibody response is detectable) serology is the mainstay of laboratory testing. The performance of cardiolipin antigen (“reagin”) and treponemal antigen (native and recombinant) tests is discussed in relation to the stage of syphilis, treatment status, and interactions between

References (44)

K. Berkowitz et al.
False-negative syphilis screening: The prozone phenomenon, nonimmune hydrops, and diagnosis of syphilis during pregnancy
Am J Obstet Gynecol
(1990)
A. Gerber et al.
Recombinant Treponema pallidum antigens in syphilis serology
Immunobiology
(1997)
H. Inagaki et al.
Gastric syphilis: Polymerase chain reaction detection of treponemal DNA in pseudolymphomatous lesions
Hum Pathol
(1996)
W.L. Risser et al.
Problems in the current case definitions of congenital syphilis
J Pediatr
(1996)
J. Anderson et al.
Primary and secondary syphilis, 20 years' experience. 3: Diagnosis, treatment, and follow-up
Genitourin Med
(1989)
S.T. Brown et al.
Serological response to syphilis treatment: A new analysis of old data
JAMA
(1985)
B. Carlsson et al.
Evaluation of the fluorescent treponemal antibody-absorption (FTA-abs) test specificity
Acta Derm Venereol Stockh
(1991)
A. Centurion-Lara et al.
Detection of Treponema pallidum by a sensitive reverse transcriptase PCR
J Clin Microbiol
(1997)
G. Chronas et al.
Syphilis diagnosis: Screening by enzyme immunoassay and variation in fluorescent antibody absorbed (FTA-abs) confirmatory test performance
Med Lab Sci
(1992)
M.C. Cummings et al.
Comparison of methods for the detection of Treponema pallidum in lesions of early syphilis
Sex Transm Dis
(1996)

Y. De Silva et al.

The value of serum TPHA titres in selecting patients for lumbar puncture

Genitourin Med

(1991)

Department of Health

Sexually transmitted diseases, England 1995: New cases seen at NHS Genito-Urinary Medicine clinics

Statistical Bulletin

(1996)

E.J. Erbelding et al.