Treponema pallidum

Categorization
Cell Wall: Gram Negative Shape: Spirochete
Metabolism: Microaerophilic
Transmission
  • The vast majority of syphilitic disease is transmitted via sexual contact. T. pallidum can also be transmitted in utero and thus classifies as part of the TORCHES Organisms.
Pathogenesis
  • T. pallidum invades through exposed mucous membranes and skin (probably through micro-abrasions) and disseminates lympho-hematogenously throughout the body within hours after infection. Consequently, patients are contagious even prior to any visible lesions. Although systemic foci of infection are established early on, the clinical consequences of syphilis follow a chronologically ordered set of events that are described as Primary, Secondary, and Tertiary Syphilis. Nearly all untreated individuals progress through the Primary and Secondary phases; however, in the majority of untreated patients the disease enters a Latent Phase where infection is detectable only by serological tests. Only a minority of patients (~30%) progress to Tertiary Syphilis. Congenital infections of syphilis possess a different natural history and are described separately below.
Morphology
  • Although the gross manifestations of syphilitic infection vary by clinical stage, a common histopathology is observed. The basic morphological feature of syphilitic infection is a proliferative inflammation of the arterial tunica intima, termed "Proliferative Endarteritis". Proliferation of endothelial cells and fibrosis in the tunica intima narrows and ultimately occludes the blood vessel. These changes are accompanied by an inflammatory infiltrate composed largely of lymphocytes and plasma cells. Pathology does not appear to be due to direct spirochete-mediated injury but rather the immune response to the organisms.
Culture and Detection
  • T. pallidum, like all spirochetes, is too small for traditional light microscopy. Darkfield microscopy along with immunofluorescence can detect the organisms in scrapings from mucocutaneous lesions; however, these techniques are rarely used for diagnosis due to the availability of serological tests.
Labs
  • Overview
    • Serological tests for the presence of anti-treponemal antibodies are the workhorse of syphilitic diagnosis. Serological tests fall into two basic categories depending on whether the antibodies analyzed are specific to the organism itself or are non-specific antibodies which can arise in different contexts. In those with deficient immunity such as AIDS Patients, infected patients may never display positive tests due to defects in the humoral immune response.
  • Nonspecific Treponemal Antibodies
    • VDRL and RPR detect antibodies to cardiolipin, a host lipid that is released as a result of syphilitic infection. Patients test positive within 1-2 weeks of inoculation and remain positive, although titers fall in some patients during latency or tertiary disease. These antibodies are used for patient screening or to detect the success of treatment as the levels of these antibodies fall as the infection is cleared. Notably, a small percentage of non-infected individuals will display False Positive results to these tests especially if patients have recently had an acute illness, are afflicted with SLE, or are IV drug abusers. Consequently, Specific Treponemal tests are always used for confirmation.
  • Specific Treponemal Antibodies
    • The FTA-Abs test detects antibodies specific for the T. pallidum organism itself and displays a much smaller false positive result rate compared to VDRL and RPR tests. Because FTA-Abs becomes positive 4-6 weeks after inoculation and is significantly more expensive, it is not used for generalized screening but rather for confirmatory diagnosis. Additionally, titers of FTA-Abs do not fall with successful treatment and so cannot be used to monitor success of therapy.
  • Basic Approach
    • VDRL/RPR pos and FTA-ABS neg = False positive
    • VDRL/RPR pos and FTA-ABS pos = Active infection
    • VDRL/RPR neg and FTA-ABS pos = Successfully treated
    • VDRL/RPR neg and FTA-ABS neg = No Syphilis, recent inoculation, or delayed immune response in AIDS Patient
Treatment
  • Penicillin G: T. pallidum is highly sensitive to penicillin and this is the drug of choice. Treatment may result in a Jarisch-Herxheimer Reaction.
Clinical Consequences