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CDC releases recent syphilis testing guidelines to combat rising cases

CDC releases recent syphilis testing guidelines to combat rising cases

In a recent report published within the Morbidity and Mortality Weekly Report (MMWR), the US (US) Centers for Disease Control and Prevention (CDC) shares its recommendations for the tests and protocols required to diagnose syphilis within the US. The recommendations construct upon existing conventional serologic algorithms and involve the combined use of nontreponemal and treponemal tests to discover if the patient’s immune response indicates a current untreated infection or a past-treated one. Moreover, recommendations for the direct microscopic detection of Treponema pallidum, the causative pathogen of syphilis, are included. These recommendations will help clinical laboratory directors, clinicians, laboratory staff, disease control personnel, and patients combat this dreadful disease.

CDC Laboratory Recommendations for Syphilis Testing, United States, 2024. Image Credit: Peddalanka Ramesh Babu / Shutterstock

Why do we’d like these recommendations?

Syphilis is a bacterial sexually transmitted infection (STI) that progresses in stages from a painless sore (stage 1) to a severe disease that will attack the brain, liver, nerves, eyes, or cardiovascular system (stage 3). Attributable to the bacterium Treponema pallidum subspecies pallidum, the disease has been further related to congenital complications akin to stillbirths, spontaneous abortions, and miscarriages.

Alarmingly, the worldwide burden of syphilis is rising rapidly, especially in wealthy and developed countries, with roughly 6 million recent cases in 2021 alone. Reports from the US of America (US) observe a rise of two,140% in syphilis incidence rates between 2000 (n = 5,979) and 2020 (n = 133,945), suggesting an area epidemic throughout the country. Research has characterised this epidemic as displaying significant health disparities, with gender and sexual minorities being the worst affected.

The laboratory diagnosis of syphilis represents a vital effort within the war against the disease. Timely diagnoses, especially before the onset of stage 3 syphilis, are critical for positive disease outcomes. Public health reporting by laboratories provides the Centers for Disease Control and Prevention (CDC) and other government agencies the knowledge needed to enact policies to attenuate local outbreaks and monitor epidemic trends.

Concerning the report

The present report details the CDC’s first-ever recommendations for syphilis testing and includes optimal methods for point-of-care (POC) tests, laboratory-based tests, sample processing, and reporting. These recommendations were formulated by CDC scientists in collaboration with the Association of Public Health Laboratories (APHL) after reviewing up-to-date peer-reviewed literature, especially publications published by the US Food and Drug Administration (FDA).

Serologic Laboratory Testing

The primary section of the report summarises progress in syphilis serological testing for the reason that invention of the Wassermann test through to current nontreponemal (lipoidal antigen) and treponemal tests. Briefly, when patients display symptoms or signs of syphilis or have had known sexual contact with a diagnosed syphilis patient, nontreponemal (lipoidal antigen) tests are really useful for laboratory screening. These tests are also really useful when assessing reinfections or reporting outcomes during clinical trials.

“Nontreponemal (lipoidal antigen) tests may be less sensitive than treponemal tests in early primary syphilis and are likely to wane with time no matter treatment. Before testing, test and specimen type ought to be rigorously considered because serum and plasma cannot all the time be used interchangeably, and certain nontreponemal (lipoidal antigen) tests require heat treatment of specimens. One caveat of nontreponemal (lipoidal antigen) tests is that a reactive result may very well be a false positive due to recent conditions (e.g., infections, vaccinations or injection drug use, or underlying autoimmune or other chronic conditions).”

Nontreponemal tests are frequently carried out manually, but some test versions (e.g., the rapid plasma reagin [RPR] test) could also be automated to extend throughput. Within the latter (automated) case especially, care should be taken to be sure that samples are maintained at optimal conditions and coinfections are accounted for to make sure diagnostic performance and forestall false positives. Treatment outcomes are best reported by comparing nontreponemal antibody titers at baseline and 12 months following treatment, at which era titers are expected to cut back fourfold.

Treponemal tests are used to validate nontreponemal test results and to diagnose early syphilis infections that can’t (yet) be detected by nontreponemal tests. Most of those tests are conducted manually, but some will be automated for top throughput. In most patients, treponemal antibodies are detectable for all times and are helpful to point a past, successfully treated syphilis infection. All donations to blood banks must undergo treponemal screening to be sure that volunteered blood is freed from syphilis antibodies.

Syphilis screening algorithms

The normal algorithm for syphilis screening involved nontreponemal tests followed by treponemal tests to verify any dubious or contentious nontreponemal results. It’s because the previous is relatively inexpensive and rapid, while the latter is manually labor-intensive, expensive, and limited in number. Nonetheless, recent advancements in automated treponemal immunoassays have bridged the time and monetary gap between these techniques, leading to the newer ‘reverse’ algorithm for syphilis screening, wherein nontreponemal tests are used to validate the outcomes of treponemal tests further.

Constructing upon these methodologies, the report provides recommendations for the optimal screening, clinical care, and recording of patients affected by neurosyphilis, ocular syphilis, otosyphilis, and congenital syphilis. Pregnancy status, specifically, is noted as a condition that mustn’t influence the usual interpretation of nontreponemal and treponemal test results attributable to scientific evidence that their functioning is just not altered while pregnant.

Direct detection tests

Immunohistochemistry and microscopy techniques for detecting syphilis from biopsies and other preserved samples are outlined with a specific give attention to darkfield microscopy (essentially the most widely used method for direct syphilis detection) and silver staining. Darkfield microscopy has been found to outperform antibody screening approaches, especially within the early stages of infection, thereby presenting itself as a great tool for early disease detection.

While Nucleic Acid Amplification Tests (NAATs) have shown great potential in accurately diagnosing syphilis infection, no FDA-approved NAATs currently exist. These recommendations are expected to be updated once FDA-approved NAATs enter the market.

Journal reference:

  • Papp JR, Park IU, Fakile Y, Pereira L, Pillay A, Bolan GA. CDC Laboratory Recommendations for Syphilis Testing, United States, 2024. MMWR Recomm Rep 2024;73(No. RR-1):1–32,  DOI: 10.15585/mmwr.rr7301a1, https://www.cdc.gov/mmwr/volumes/73/rr/rr7301a1.htm


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