Syphilis Serology: Test, Diagnosis & Interpretation

Instructor: Lori Haag

Lori has teaching experience in the health care setting. She has an associate's degree in Nursing and a bachelor's degree in Psychology.

In this lesson you will learn about: the bacteria that causes syphilis, tests used to confirm a syphilis infection, and complications in interpreting serological tests. You will also become familiar with the stages of syphilis and the sensitivity of tests used in each stage.

Dr. Daze is Confused!

Dr. Daze looked at the chart in front of him but was confused by the numbers. He vividly remembers the genital sores the patient showed him, but he can't remember why he ran all these tests. The positives, the negatives, the asterisks...what did this all mean? Apparently Dr. Daze needed to brush up on syphilis testing and interpretation. In the meantime, he was going to consult another doctor to help him decipher this mess.

Syphilis is a sexually transmitted disease caused by the bacteria Treponema pallidum, T. pallidum. Confirmation of a syphilis infection requires a thorough sexual history, a physical examination, and positive results from several serological tests. Interpretation of test results can be extremely confusing, even for professionals. There are many tests that can be used in helping to determine whether or not an infection is present, however some tests that are used are not specific to syphilis alone and some of the markers may be present for long periods of time after an infection has occurred. Determining the presence of infection is critical because syphilis can be cured with antibiotics, preventing the disease from progressing to the next stage. Understanding the stages of syphilis is critical to the interpretation of serological testing because sensitivity to these tests differs with each stage.

A syphilis diagnosis requires serological testing.
Blood tube

Primary Syphilis

This is the first stage of the disease that occurs following an incubation period of up to 21 days. This stage is characterized by painless sores referred to as chancres. The chancres are rich in contagious material, and therefore direct contact with these lesions can result in transmission of the disease. The lesions generally appear at the point of contact, such as the genitals, the anus, or the mouth. Fluid from the chancre can be collected and examined directly under a microscope to determine if Treponema pallidum is present. A PCR, or Polymerase Chain Reaction test, can also be done on the fluid to detect the presence of T. pallidum DNA. However, this test is not used as conclusive evidence alone for a positive diagnoses of syphilis infection because its sensitivity rate ranges from 70-95%. The sensitivity of a test refers to its ability to correctly identify individuals with a certain disease. For example, if 100 people are known to have a syphilis infection, but a certain test shows positive results for only 90 people, the test has a 90% sensitivity rate. This means that 10 of the patients who actually have syphilis have false-negative results. For this reason, accompanying serological testing and clinical manifestation of the disease are needed to confirm a syphilis infection.

Secondary Syphilis

If the primary stage of syphilis goes untreated, the syphilis infection can progress to the secondary stage. Chancres may or may not be present, but a rash develops. This rash usually presents as rough reddish-brown spots on the palms of the hands and soles of the feet. In some cases, the rash is so faint that it is not noticeable. If there are no chancres, the PCR and microscopic studies cannot be done to determine the presence of T. pallidum. If a syphilis infection is suspected, serological tests will need to be performed to confirm a diagnosis.

Treponemal Tests

There are two types of serological tests which can be performed to determine the presence of a syphilis infection. Treponemal tests detect antibodies or antigens to treponemal agents. They are specific to treponemes but not necessarily to T. pallidum and can be positive in the event of a different treponemal infection. Yaws, pinta, and bejel are treponemal infections which are native to South America and Africa. Serology tests cannot differentiate between these treponemal infections. A positive treponemal test will likely be followed by a non-treponemal test to confirm a diagnosis. The treponemal tests available in the United States are:

  • FTA-ABS - Fluorescent treponemal antibody absorption
  • MHA-TP - Microhemagglutination test for antibodies to T. pallidum
  • TPPA - T. pallidum particle agglutination assay
  • TP-EIA - T. pallidum enzyme immunoassay
  • CIA - Chemiluminescence immunoassay

Non-Treponemal Tests

Non-treponemal tests are not specific to treponemal infections but instead detect antibodies to a different antigen which is present during infections. Non-treponemal tests are often used to monitor treatment because levels decrease with successful treatment of the infection. Some laboratories will start with a non-treponemal test which will then be followed with a treponemal test. The non-treponemal tests that are used are:

  • RPR - Rapid plasma reagin
  • VDRL - Venereal Disease Research Laboratory
  • TRUST - Toluidine Red Unheated Serum Test

Unlike the primary stage, the RPR, VDRL, and TRUST all have a 100% sensitivity rate during secondary syphilis.

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