Syphilis, once known as the ‘Great Pox’, continues to challenge clinicians with its nuances in diagnosis and management. Serologic tests are the foundation of syphilis management because Treponema pallidum (TP) cannot be cultured in vitro, and knowledge of their diagnostic limitations is critical for clinicians. The mainstay of diagnosis for T. pallidum infections is based on non-treponemal and treponemal serologic tests.
Sensitivities of non-treponemal tests vary depending on the type of test and stage of infection, with lower sensitivities in primary syphilis and late syphilis. False-positive test results are associated with viral infections, pregnancy, malignant neoplasms, autoimmune diseases, and advanced age while false negatives are observed due to detection of lipodial antibody detection appearing later during infection.
Commercial ELISA tests have been developed since the World Health Organization recommended the use of a combination of a non-treponemal and treponemal test for screening and diagnostic purposes to minimise the risk of syphilis infection through the route of transfusion
Recommendations
- Screening should be performed using a highly sensitive and specific test for treponemal antibodies: either TPHA or enzyme immunoassay (ELISA)
- In populations where there is a high incidence of syphilis, screening should be performed using a non-treponemal assay: VDRL or RPR.
In India, syphilis continues to be a major health problem. However, a constant decline in its prevalence has been observed in recent years. In the current scenario, use of treponemal ELISA has become the first choice of preference to screen population with early or very late stage of infection in which non-treponemal tests are negatives. This helps in better treatment management and eradicating the incidence either through transmission or transfusion.
|
Kejal Mistry
|
Since treponemal serology is relatively complex with different profiles seen at different stages of infection and depending on whether treatment has been given or not, detection of total antibodies (IgM, IgG and IgA) helps in screening samples of any type or at any stage of infection. Serum immunoglobulin IgM and IgG antibody responses to T. pallidum have been studied extensively. Anti treponemal IgM antibodies are produced approximately two weeks after exposure, followed by IgG antibodies two weeks after IgM production.
A recent report suggested that new recombinant antigen-based treponemal IgG and IgM ELISAs are the most sensitive, highly specific treponemal tests, and thus suitable for screening.
Furthermore, the advantages of the ELISA format include the production of objective results, the ability to link ELISA plate readers directly to laboratory computer systems (reducing the potential for errors transcribing results), and the facility for automation.
Algorithm for syphilis screening by Treponemal ELISA
The reversal of traditional syphilis algorithms using treponemal ELISAs for screening has led to uncertainty in clinical management. The CDC encourages clinicians to consider treatment for late latent syphilis in individuals with positive treponemal ELISA results to reduce the chance of progression to tertiary complications. Important considerations with the new syphilis tests are their Positive Predictive Value (PPV) and Negative Predictive Value (NPV), which depends on the disease prevalence in the population tested. Highly sensitive treponemal ELISAs will be beneficial for diagnosis of patients with suspected syphilis and with no prior history, especially in early or late infections with non-reactive, non-treponemal tests.
Globally, VDRL and TPHA combination is being increasingly replaced with ELISA tests that detect treponemal IgG or IgG and IgM. The recent commercial availability of ELISA has made it a method of choice for screening, the world over.
(Recently, Transasia has launched ErbaLisa Syphilis for detection of total antibodies against Treponema pallidum. ErbaLisa Syphilis utilises recombinant antigens of TP which ensures higher diagnostic sensitivity and specificity as compared to non-treponemal tests in case of primary, tertiary and congenital syphilis. It also minimises the cross reactivity with cardiolipin antibodies. These factors make ErbaLisa Syphilis attractive for laboratories with large workloads.)