Syphilis testing guide: From etiology to serology, everything is covered

Author: Lou Jinli, researcher/professor at Beijing You'an Hospital, Capital Medical University

Reviewer: Wang Lixiang, Chief Physician, Third Medical Center, PLA General Hospital

The 10th Chairman of the Science Popularization Branch of the Chinese Medical Association

Syphilis is a chronic infectious disease caused by Treponema pallidum, which is mainly transmitted through sexual contact, but can also be transmitted from mother to child or through blood. Once syphilis is suspected, it is crucial to conduct professional medical examinations in a timely manner to ensure early diagnosis and treatment, and avoid worsening of the disease and complications. The following will introduce in detail the examination methods and significance of syphilis, aiming to help readers better understand the diagnosis process of syphilis.

Syphilis tests can be roughly divided into two categories: etiological tests and serological tests. Etiological tests refer to methods that directly detect pathogens, such as dark field microscopy, silver staining, PCR, and immunofluorescence. These methods can provide direct evidence of pathogens and are of great significance for the diagnosis of syphilis.

Figure 1 Original copyright image, no permission to reprint

As a method for directly detecting pathogens, dark field microscopy plays an important role in the diagnosis of syphilis. This technology uses a specially designed microscope to make the spirochetes in the specimen appear as bright outlines against a dark background, making it easier to observe their morphology and activity. However, this method has high requirements for sampling, especially in late syphilis or after treatment, because the number of spirochetes decreases, the difficulty of detection increases, and sometimes multiple and multi-site sampling may be required to obtain an accurate diagnosis. Therefore, even if the initial test result is negative, the possibility of syphilis should not be easily ruled out, and other serological examination methods should be combined for comprehensive judgment when necessary.

Serological examination indirectly determines whether the patient is infected by detecting antibodies against Treponema pallidum in the patient's blood. Serological examination is divided into non-specific Treponema pallidum antigen serological test and specific Treponema pallidum antigen serological test. The former includes the Venereal Disease Research Laboratory Test (VDRL), the Rapid Reactin Ring Card Test (RPR) and the Toluidine Red Unheated Serum Test (TRUST), etc. These tests mainly detect the non-specific antibodies - reagin produced by the body after skin and mucous membrane damage caused by Treponema pallidum infection. The latter includes the Treponema pallidum gelatin particle agglutination test (TPPA), the Treponema pallidum hemagglutination test (TPHA), the enzyme-linked immunosorbent assay (ELISA), etc., which directly detect antibodies against Treponema pallidum specific antigens. Serological examination is widely used in clinical practice because of its simple operation and high sensitivity.

It is worth noting that the results of serological tests for syphilis require comprehensive analysis. For example, when the specific antibody test result is negative, a further nonspecific antibody RPR or TRUST test is required. If both results are negative, syphilis infection can be basically ruled out. If the specific antibody is weakly positive, multiple factors need to be considered, such as false positive results that may be caused by autoimmune diseases, and a comprehensive evaluation should be conducted in combination with the RPR or TRUST test results. If both the specific antibody and RPR or TRUST tests are positive, especially when the RPR or TRUST titer is high, it can be used as one of the bases for confirming syphilis infection.

Regarding the time of diagnosis of syphilis, it is generally believed that the human body begins to produce detectable specific antibodies about 3-4 weeks after infection, and it is more appropriate to conduct serological tests at this time. However, considering individual differences, it is recommended to wait at least 3-4 weeks after high-risk behavior before conducting an examination, and if the initial test result is negative, re-examination should be conducted after 2-3 months to ensure the accuracy of the diagnosis. In addition, the diagnosis of syphilis does not only rely on laboratory test results, but also needs to be combined with the patient's clinical symptoms, physical signs, epidemiological history and other information, and a professional doctor must make the final judgment.

Figure 2 Original copyright image, no permission to reprint

Finally, the interpretation of syphilis antibody titers should also be cautious. The titers of non-specific antibodies such as RPR or TRUST reflect the activity of Treponema pallidum in the body and the severity of damage to the body. However, the titer is also affected by many factors, such as treatment response, recurrence, etc., so it is an indicator for monitoring current infection and drug efficacy. Therefore, when interpreting the antibody titer results, a comprehensive judgment should be made in combination with the patient's medical history, clinical symptoms and signs.