Origin of Nontreponemal Antibodies During Treponema pallidum Infection: Evidence From a Rabbit Model

Gao, Kun; Shen, Xu; Lin, Yong; Zhu, Xiao-Zhen; Lin, Li‐Rong; Tong, Man‐Li; Xiao, Yao; Zhang, Huilin; Liang, Xianming; Niu, Jianjun; Liu, Li‐Li

doi:10.1093/infdis/jiy241

Cited by 32 publications

(22 citation statements)

References 25 publications

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“…Both rabbits that were inoculated with CDC-SF003 and CDC-SF007 developed treponemal antibodies first as shown by TP-PA when compared to the nontreponemal antibodies measured by RPR. This observation is in agreement with previous reports for both the rabbit model and patients diagnosed with syphilis, where treponemal antibodies have been shown to develop prior to nontreponemal antibodies [10][11][12][66][67][68], albeit treponemal antibody detection in patients does not always distinguish among recent, past, and previously treated infection. The relatively rapid development of orchitis and/or seroreactivity in the second passage rabbits for CDC-SF003 and CDC-SF007 compared to the first is consistent with serial passage described in previous studies and is attributed in part to a more concentrated starting inoculum, and genetic diversification and adaptation of T. pallidum in the rabbit model [9,27,28].…”

Section: Discussionsupporting

confidence: 93%

Successful isolation of Treponema pallidum strains from patients’ cryopreserved ulcer exudate using the rabbit model

et al. 2020

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Clinical isolates of Treponema pallidum subspecies pallidum (T. pallidum) would facilitate study of prevalent strains. We describe the first successful rabbit propagation of T. pallidum from cryopreserved ulcer specimens. Fresh ulcer exudates were collected and cryopreserved with consent from syphilis-diagnosed patients (N = 8). Each of eight age-matched adult male rabbits were later inoculated with a thawed specimen, with two rabbits receiving 1.3 ml intratesticularly (IT), and six receiving 0.6 ml intravenously (IV) and IT. Monitoring of serology, blood PCR and orchitis showed that T. pallidum grew in 2/8 rabbits that were inoculated IV and IT with either a penile primary lesion specimen (CDC-SF003) or a perianal secondary lesion specimen (CDC-SF007). Rabbit CDC-SF003 was seroreactive by T. pallidum Particle Agglutination (TP-PA) and Rapid Plasma Reagin (RPR) testing, PCR+, and showed orchitis by week 6. Euthanasia was performed in week 7, with treponemal growth in the testes confirmed and quantified by qPCR and darkfield microscopy (DF). Serial passage of the extract in a second age-matched rabbit also yielded treponemes. Similarly, rabbit CDC-SF007 showed negligible orchitis, but was seroreactive and PCR+ by week 4 and euthanized in week 6 to yield T. pallidum, which was further propagated by second passage. Using the 4-component molecular typing system for syphilis, 3 propagated strains (CDC-SF003, CDC-SF007, CDC-SF008) were typed as 14d9f, 14d9g, and 14d10c, respectively. All 3 isolates including strain CDC-SF011, which was not successfully propagated, had the A2058G mutation associated with azithromycin resistance. Our results show that immediate cryopreservation of syphilitic ulcer exudate can maintain T. pallidum viability for rabbit propagation.

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Section: Discussionsupporting

confidence: 93%

Successful isolation of Treponema pallidum strains from patients’ cryopreserved ulcer exudate using the rabbit model

et al. 2020

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“…The Nichols strain was kindly donated by Lorenzo Giacani, PhD (University of Washington, Seattle, USA) and was maintained as previously described (Gao et al, 2018). The strain was propagated intratesticularly in adult male New Zealand white rabbits.…”

Section: Propagation Of Tpmentioning

confidence: 99%

Treponemapallidum Dysregulates Monocytes and Promotes the Expression of IL-1β and Migration in Monocytes Through the mTOR Signaling Pathway

Liu

Jiang

et al. 2020

Front. Cell. Infect. Microbiol.

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“…This release of cardiolipin antigens induces the production of reagin. [19][20][21] Therefore, this may be a potential reason for the post-treatment increase in titer (instead of a decrease) observed in some patients with early syphilis. Other reasons may include inter-individual variability with respect to the immune response to T. pallidum.…”

Section: Discussionmentioning

confidence: 99%

Post-treatment serological changes in some patients with early syphilis exhibit a parabolic trend

et al. 2019

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Early syphilis accounts for a large proportion of patients with syphilis. Non- Treponema pallidum tests are commonly used to assess treatment effectiveness by analyzing the serological titer before treatment and six months after treatment. However, serological changes during the first three months after completion of treatment have not been completely understood. This prompted us to investigate whether serum titers of patients exhibit a continuous decrease post-treatment and to assess the trend of change in serological titer during this period. One hundred and seventy-three eligible patients with early syphilis were included in the analysis. Pre-treatment serological titers and those at three and six months post-treatment were compared and analyzed. Serological recovery was defined as a 4-fold or greater decrease in titer from pre-treatment level. Forty patients (23.1%) were found to have an increased serum titer at three months after treatment. Among the 40 patients, 13 patients had primary syphilis, 5 patients had secondary syphilis, and 22 patients had early latent syphilis. The proportion of patients with primary syphilis was higher, and their initial titers were significantly lower. No significant differences were observed with respect to age, gender, or initial treatment. The assessment results of 17 patients (9.8% of the total patients) change. Serological changes in some patients exhibit a parabolic pattern that may affect the clinician’s assessment of patient recovery. Therefore, more frequent assessment of serological titer might be required within the first six months post-treatment.

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Origin of Nontreponemal Antibodies During Treponema pallidum Infection: Evidence From a Rabbit Model

Cited by 32 publications

References 25 publications

Successful isolation of Treponema pallidum strains from patients’ cryopreserved ulcer exudate using the rabbit model

Successful isolation of Treponema pallidum strains from patients’ cryopreserved ulcer exudate using the rabbit model

Treponemapallidum Dysregulates Monocytes and Promotes the Expression of IL-1β and Migration in Monocytes Through the mTOR Signaling Pathway

Post-treatment serological changes in some patients with early syphilis exhibit a parabolic trend

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