Laboratory diagnosis and interpretation of tests for syphilis

Abstract

The lack of a method for demonstrating the presence of Treponema pallidum by growth necessitates the use of alternative methods. Traditionally, these methods are divided into direct detection methods (animal inoculation, dark-field microscopy, etc.) and serologic tests for the presence of patient antibody against T. pallidum. Serologic methods are further divided into two classes. One class, the nontreponemal tests, detects antibodies to lipoidal antigens present in either the host or T. pallidum; examples are the Venereal Disease Research Laboratory and rapid plasma reagin and tests. Reactivity in these tests generally indicates host tissue damage that may not be specific for syphilis. Because these tests are easy and inexpensive to perform, they are commonly used for screening, and with proper clinical signs they are suggestive of syphilis. The other class of test, the treponemal tests, uses specific treponemal antigens. Confirmation of infection requires a reactive treponemal test. Examples of the treponemal tests are the microhemagglutination assay for antibodies to T. pallidum and the fluorescent treponemal antibody absorption test. These tests are more expensive and complicated to perform than the nontreponemal tests. On the horizon are a number of direct antigen, enzyme-linked immunosorbent assay, and PCR techniques. Several of these techniques have shown promise in clinical trials for the diagnosis of congenital syphilis and neurosyphilis that are presently difficult to diagnose.

Late-stage neurosyphilis presenting with severe neuropsychiatric deficits: diagnosis, therapy, and course of three patients

“…Elevation of CSF total protein levels and CSF-VDRL have not been reported to inevitably decrease after a sufficient treatment in many cases, especially in HIV-positive patients [18,19]. Also, blood-brainbarrier dysfunction was reported to frequently remain abnormal in patients with treated neurosyphilis [13,15]. Specific treponemal tests (TPPA, TPHA titer) in serum and CSF as well as the specific antibody index (TPHA index) may remain positive lifelong following effective treatment, and can therefore not be used as specific followup parameters [13,15].…”

“…This assay is the most sensitive method [33], but is rarely available and is time-consuming. Dark-field examination, demonstrating the motility of the organisms [34], and direct fluorescent antibody (DFA) tests in the serum are the diagnostic methods of choice for early syphilis; however, they are not sensitive enough for detecting T. pallidum in the CSF [13,16]. Newer technologies like the DNA-PCR have not reached sufficient sensitivity yet in comparison to the RIT [33].…”

“…Diagnosis of neurosyphilis was then established by positive results of TPPA reactions in blood (1:81920) and CSF samples (1:8192) in combination with a pathological antibody-specific index of 12.3 against T. pallidum (the index was calculated according to Prange et al [13], thus corrected to total IgG, and additionally corrected to albumin). At this time, CSF revealed a normal cell count and normal total protein level, possibly due to the previous treatment with ceftriaxone.…”

“…For follow-up, CSF-WBC and CSF-VDRL are the most reliable parameters [3,16,17]. Normalization of specific serological reactions in serum and CSF after treatment can be delayed or even fail to appear [10,13,18,19], but this does not necessarily signify a failure of treatment. Therefore, a decision to treat or, particularly, retreat during follow-up based on laboratory findings can be difficult.…”

“…Generally, to reliably assess the activity of neurosyphilis, in order to make a therapeutic decision, a combination of several CSF abnormalities including elevations of CSF white blood cell count (WBC) or total protein concentration and pathological T. pallidum particle agglutination (TPPA) or T. pallidum hemagglutination assay (TPHA) or venereal disease research laboratory (VDRL) titers and an elevated antibody-specific (TPHA) index against T. pallidum in blood and CSF must be interpreted in relation to each other and to the clinical status [13][14][15]. For follow-up, CSF-WBC and CSF-VDRL are the most reliable parameters [3,16,17].…”