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

Lin, Li‐Rong; Zhu, Xiao-Zhen; Liu, Deyun; Liu, L.-L.; Tong, Man‐Li

doi:10.1016/j.cmi.2019.06.004

Cited by 13 publications

(8 citation statements)

References 20 publications

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“…Indeed, the rabbit that was injected with CDC-SF007, which successfully grew in vivo, did not show any discernible orchitis even when seroreactive and PCR+, while the rabbit with CDC-SF003 developed orchitis beginning in week 6 when an increase in antibody titers was first noted. Consistent with previous studies [9,26,61,64,65], these observations indicate that including additional detection methods for treponemal propagation in rabbits can avoid overlooking an active infection that could inadvertently be cleared by the immune response before treponemal harvest can be performed. Of note, when comparing serology and PCR, both methods generally showed a reactive or positive result at comparable time points post infection for a given rabbit, which aligns with a previous study [61].…”

Section: Discussionsupporting

confidence: 89%

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: 89%

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

et al. 2020

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“…Our data showed that the RPR titer could decrease more than fourfold before treatment, which means that the treatment success criteria could be achieved without treatment in some patients. In a rabbit model, non-treponemal titers increased after infection and then spontaneously decreased more than fourfold within 6 months even without treatment [ 8 ]. Even after the RPR titer became negative, however, viable T .…”

Section: Discussionmentioning

confidence: 99%

“…However, some researchers and clinicians have reported that the nontreponemal titer could change without treatment. In a rabbit model of syphilis infection, the natural course of the nontreponemal titer shows a bell-shaped curve with a longer right tail; the titer increases shortly after inoculation, then decreases gradually, and can become negative even without treatment [ 8 ]. We hypothesized that if nontreponemal titer increases and decreases spontaneously in humans, then pre-treatment changes in nontreponemal titer might affect post-treatment response.…”

Section: Introductionmentioning

confidence: 99%

Changes in rapid plasma reagin titers in patients with syphilis before and after treatment: A retrospective cohort study in an HIV/AIDS referral hospital in Tokyo

Ikeuchi,

Fukushima,

Tanaka

et al. 2023

PLoS ONE

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Introduction Although the rapid plasma reagin (RPR) test is used to determine treatment efficacy for syphilis, animal studies show that it decreases gradually after an initial increase even without treatment. Pre-treatment changes in RPR titer in humans and its relationship with post-treatment changes in RPR titer are not well known. Methods We retrospectively analyzed the clinical records of syphilitic patients who underwent automated RPR (Mediace) testing twice before treatment (i.e., at diagnosis and treatment initiation) within 1–3 months at an HIV/AIDS referral hospital in Japan between 2006 and 2018. The RPR values were expressed as the ratio to the value at treatment initiation. The mean monthly relative change in the RPR after treatment was calculated on the log2 scale for each patient and analyzed by multivariable linear regression. Results Sixty-eight patients were identified. The median age was 45 (interquartile range [IQR], 38–50), 98.5% (67/68) were men, and 97.1% (66/68) had HIV. The median RPR titer ratio at treatment initiation/diagnosis was 0.87 (IQR, 0.48–1.30). The RPR titer decreased more than twofold in 26.5% (18/68) and more than fourfold in 10.3% (7/68) before treatment. In the multivariable analysis, higher age (predicted monthly RPR relative change on the log2 scale 0.23/10 years [95% confidence interval [CI], 0.090–0.37]), history of syphilis (0.36 [95% CI, 0.07–0.65]), and a lower ratio of RPR at treatment initiation/diagnosis (−0.52/every 10-fold increase [95% CI, −0.81 to −0.22]) were associated with a slower RPR decrease after treatment. Conclusions In a mostly HIV patient population, RPR titer can show more than four-fold spontaneous increase or decrease within 1–3 months. Pre-treatment spontaneous decrease of RPR titer was associated with a slower decrease in post-treatment RPR titer.

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“…For example, recovery from syphilis is traditionally dependent on the detection of nontreponemal rapid plasma reagin titers. However, it was proposed that titers are not as relevant to the prognosis of syphilis as might be expected [ 176 ]. Thus, epitopes in infection phase-dependent antigens are promising to evaluate the recovery of syphilis [ 177 ].…”

Section: Discussionmentioning

confidence: 99%

A Promising Tool in Serological Diagnosis: Current Research Progress of Antigenic Epitopes in Infectious Diseases

et al. 2022

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Infectious diseases, caused by various pathogens in the clinic, threaten the safety of human life, are harmful to physical and mental health, and also increase economic burdens on society. Infections are a complex mechanism of interaction between pathogenic microorganisms and their host. Identification of the causative agent of the infection is vital for the diagnosis and treatment of diseases. Etiological laboratory diagnostic tests are therefore essential to identify pathogens. However, due to its rapidity and automation, the serological diagnostic test is among the methods of great significance for the diagnosis of infections with the basis of detecting antigens or antibodies in body fluids clinically. Epitopes, as a special chemical group that determines the specificity of antigens and the basic unit of inducing immune responses, play an important role in the study of immune responses. Identifying the epitopes of a pathogen may contribute to the development of a vaccine to prevent disease, the diagnosis of the corresponding disease, and the determination of different stages of the disease. Moreover, both the preparation of neutralizing antibodies based on useful epitopes and the assembly of several associated epitopes can be used in the treatment of disease. Epitopes can be divided into B cell epitopes and T cell epitopes; B cell epitopes stimulate the body to produce antibodies and are therefore commonly used as targets for the design of serological diagnostic experiments. Meanwhile, epitopes can fall into two possible categories: linear and conformational. This article reviews the role of B cell epitopes in the clinical diagnosis of infectious diseases.

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

Cited by 13 publications

References 20 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

Changes in rapid plasma reagin titers in patients with syphilis before and after treatment: A retrospective cohort study in an HIV/AIDS referral hospital in Tokyo

A Promising Tool in Serological Diagnosis: Current Research Progress of Antigenic Epitopes in Infectious Diseases

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