A negative nontreponemal and/or specific antitreponemal IgM test does not exclude active infectious syphilis

Abstract

Background:The diagnostic criteria for active infectious syphilis in the clinic are important matter of controversy and debate. So far, clinicians habitually do use the negative results of the nontreponemal and/or the specific antitreponemal IgM as the evidences of disease-free or active infection-free status.Method:We present a case study involving a patient who was admitted to Zhongshan Hospital because of cerebral infarct. Clinical examination indicated he had a history of latent syphilis with negative nontreponemal and specific antitreponemal IgM tests. The cerebrospinal fluid sample from the patient was inoculated into seronegative New Zealand rabbit.Results:Motile Treponema pallidum was detected by a rabbit infectivity test in the patient's cerebrospinal fluid. This syphilis strain was confirmed by DNA subtyping form of “centers for disease control subtype/tp0548 sequence type”, and the strain type was 14d/f. Treatment with benzathine penicillin provided no apparent benefit, but treatment with aqueous crystalline penicillin G, especially recommended for neurosyphilis, led to disease regression. No evidence of cerebral infarct was observed during a 2-year follow-up period.Conclusion:The definitive differential diagnosis of active infectious syphilis should be reconsidered. Moreover, selecting the appropriate penicillin preparation is important because T pallidum can reside in sequestered sites. It is necessary to treat a patient with known invasion of the central nervous system with aqueous crystalline penicillin G, if previous treatment for syphilis failed and patients had some clinical neurological presentation that is otherwise unexplained, but that could represent neurosyphilis. Additional studies are needed to confirm the results in other syphilis patients.

Are nontreponemal tests suitable for monitoring syphilis treatment efficacy? Evidence from rabbit infection models

“…We observed a continual increase in the RPR titre for a period of time following the first BPG treatment, consistent with the finding of Holman et al [13]. Moreover, previous studies showed that a fourfold decline in the RPR titre and even seronegativity in treated patients did not preclude the development of infection [12,14]. These findings suggested that the RPR titre might not be closely related to the treatment efficacy, and we instead recalled a specific feature of syphilis, the appearance of spontaneous resolution.…”

“…In addition, Holman et al found that approximately 20% of patients exhibited an increase of at least one dilution instead of a decrease in the RPR titre during the 14-day following therapy [13]. More surprisingly, we isolated a virulent T. pallidum strain of type 14d/f from the cerebrospinal fluid of a patient with syphilis with a negative serum RPR test after recommended treatment [14]. These findings constantly challenge the concept that 'RPR titres are suitable for monitoring treatment efficacy'.…”

Advances in laboratory diagnostic methods for cerebrospinal fluid testing for neurosyphilis

“…MIF is a key indicator of central nervous system infection. Studies have shown that the sensitivity of CSF MIF concentration for neurosyphilis diagnosis was 74.42%, and the specificity was 67.74% (42). The MIF level was higher in the CSF of neurosyphilis patients than in syphilis/non-neurosyphilis patients.…”

Laboratory Diagnostic Tools for Syphilis: Current Status and Future Prospects

“…It is noteworthy that the criterion of the decline in the RPR titers to assess syphilis or neurosyphilis treatment has been recommended by a few guidelines ( Janier et al., 2014 ; Xiao et al., 2017a ). Nevertheless, a study showed that virulent T. pallidum remained viable in a patient with a negative serum RPR test after treatment ( Lin et al., 2016 ). Recently, Lin et al.…”