Development of a syphilis serum bank to support research, development, and evaluation of syphilis diagnostic tests in the United States

Abstract

The Centers for Disease Control and Prevention’s (CDC) Division of STD Prevention, in collaboration with the Association of Public Health Laboratories (APHL), is developing a nationally available syphilis serum repository for research of Food and Drug Administration (FDA)-cleared or investigational syphilis diagnostic assays in the United States. State and local public health laboratories (PHL) submitted de-identified residual sera with information on collection date, volume, storage conditions, freeze-thaw cycles, PHL serology results, reported syphilis stage and demographic details if available. Previous test results were blinded and sera (N=152 reported syphilis stage, N = 131 unknown status) were tested at CDC using five FDA-cleared and one investigational syphilis tests. Treponemal and nontreponemal test sensitivity ranged from 76.3–100% and 63.2–100%, respectively, among staged specimens. The conventional treponemal assays showed high concordance of 95.4%. By providing syphilis stage and comprehensive serological test data, developed repository may serve as a valuable resource for diagnostic test validation studies.

Development of a novel magnetic particle-based agglutination immunoassay for anticardiolipin antibody detection in syphilis

“…Using laboratory characterised syphilis specimens, both NT-MAA and RPR demonstrated similar sensitivity for primary, secondary and early latent staged specimens that were evaluated. The late latent staged specimens revealed reduced sensitivity by both non-treponemal tests and align with a prior report, 18 though the NT-MAA was noted to have slightly more sensitivity than the RPR. The sensitivity of a non-treponemal test in the context to syphilis stage may vary and described in prior studies.…”

“…In the interim, syphilis serum bank is being continuously developed to obtain a greater number of characterised specimens for future validation of NT-MAA for syphilis. 18 Of note, intrinsic differences in the underlying assay mechanism and its impact on test performance cannot be ruled out, as the standard RPR is based on the flocculation principle where activated charcoal particles facilitate visualisation of the antigen-antibody complexes in reactive specimens, while the NT-MAA involves visible agglutination as a result of a direct on October 31, 2020 by guest. Protected by copyright.…”

“…In the interim, syphilis serum bank is being continuously developed to obtain a greater number of characterised specimens for future validation of NT-MAA for syphilis. 18 Of note, intrinsic differences in the underlying assay mechanism and its impact on test performance cannot be ruled out, as the standard RPR is based on the flocculation principle where activated charcoal particles facilitate visualisation of the antigen–antibody complexes in reactive specimens, while the NT-MAA involves visible agglutination as a result of a direct binding between cardiolipin-coupled magnetic microbeads and the antibody. The suitability of the NT-MAA for other specimen types like cerebrospinal fluid (CSF) remains unexplored and could facilitate development of an alternative platform to CSF-VDRL that is currently widely used for neurosyphilis diagnosis.…”

“…A panel of 371 archived, deidentified frozen serum specimens was prepared at the CDC (Atlanta, Georgia, USA). Of these, 127 syphilis specimens were obtained from the CDC's syphilis serum repository bank, 18 originally procured from the Association of Public Health Laboratory (APHL, Silver Spring, Maryland, USA) through an ongoing collaborative agreement beginning in 2015 . Syphilis stage of those specimens was reported by the participating local and state public health laboratories to the APHL from the test request form.…”

The Israel National Sera Bank: Methods, Representativeness, and Challenges

“…The Netherlands established a national serum bank that aimed to evaluate the National Immunization Program [ 19 ], similar to the INSB. The U.S. Centers for Disease Control and Prevention presented a repository of serum samples collected for specific purposes [ 20 ]. Despite these initiatives, as has been suggested, a World Serology Bank, in contrast to national serum banks established locally, could be helpful in optimizing vaccination strategies and in the global task of eradicating vaccine-preventable infections such as polio, measles, and rubella [ 2 ].…”