Detection of the host's immune response to infection has been the mainstay of the diagnosis of syphilis for decades. Serological characterisation of Treponema pallidum infection presents a number of challenges including the life-long antibody response to treponemal antigens following primary infection, absence of a test specific only to T pallidum and lack of a test detecting treponemal antibody that indicates newly acquired infection or response to treatment. Non-treponemal or reagin-based tests offer the best indication of infectious syphilis but themselves can show cross-reactivity to other infections and conditions. These challenges are coupled in much of the developed world with very low rates of infection.
The choice for screening or testing individuals for syphilis can be difficult in that the treponemal tests such as the enzyme immunoassays and chemiluminescent assays, are highly sensitive, can be automated and allow screening of large numbers of sera, whereas the rapid plasma reagin (RPR) test is an agglutination test, cannot be automated and does not easily lend itself to large scale testing. In England & Wales, the National Standard Operating Procedure (VSOP 44) and the Antenatal Screening Committee Laboratory Standards both recommend screening using an enzyme immunoassays, or chemiluminescent assays, followed by confirmation by the Treponemal Passive Particle Assay, to eliminate any non-specific reactivity. Sera giving a positive reaction with both tests will then be immediately tested using the RPR.
The advantages of this approach are that large numbers of sera can be screened in local laboratories, where most will give a negative result, allowing the small number of potentially infected individuals to be quickly identified for further testing. There may be a resulting delay in identifying an infectious case particularly in low prevalence populations, where the laboratory may not perform the confirmatory tests and refers to a regional centre and therefore standards for turnaround times and rapid referral to a specialist physician to ensure timely treatment, especially in maternal syphilis, are essential. In high prevalence areas the RPR is likely to be more cost-effective as a screening test, however, the approach taken should address the population to be tested, the laboratory resources for screening / testing and the prevalence of infection to identify and treat the maximum number of cases for the public health control of syphilis.