Persistence of T. pallidum and its significance in penicillin-treated seropositive late syphilis.

Yogeswari, L; Chacko, C W

doi:10.1136/sti.47.5.339

Cited by 14 publications

(9 citation statements)

References 8 publications

(8 reference statements)

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“…Moreover, whilst the clearance of bacterial DNA was measured, it is unknown whether the DNA detected was from living or dead organisms. As T. pallidum is non-culturable, Rabbit Infectivity Testing (RIT), where test animals are injected with clinical material in order to propagate and identify T. pallidum , could have been used to assess persistence following treatment [ 19 , 20 ]. This approach would, however, have required the sacrifice of a large number of animals.…”

Section: Discussionmentioning

confidence: 99%

Rapid Treponema pallidum Clearance from Blood and Ulcer Samples following Single Dose Benzathine Penicillin Treatment of Early Syphilis

et al. 2015

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Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum), is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene) and RNA (16S rRNA) quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53). The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84). From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08x107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20–56) after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies.

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Section: Discussionmentioning

confidence: 99%

Rapid Treponema pallidum Clearance from Blood and Ulcer Samples following Single Dose Benzathine Penicillin Treatment of Early Syphilis

et al. 2015

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“…Treponemes may persist despite apparently successful treatment indicating that some treponemes may be ‘resting’ or dividing very slowly . 68–73 Clinical data are lacking on the optimal dose and duration of treatment and the long-term efficacy of antimicrobials other than penicillin. The recommendations are based mainly on laboratory considerations, biological plausibility, expert opinion, case studies and clinical experience. Parenteral rather than oral treatment has been the treatment of choice because therapy is supervised and bioavailability is guaranteed. Non-penicillin antibiotics that have been evaluated include doxycycline, erythromycin and azithromycin.…”

Section: Management: General Considerationsmentioning

confidence: 99%

UK national guidelines on the management of syphilis 2015

Kingston¹,

et al. 2015

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These guidelines are an update for 2015 of the 2008 UK guidelines for the management of syphilis. The writing group have piloted the new BASHH guideline methodology, notably using the GRADE system for assessing evidence and making recommendations. We have made significant changes to the recommendations for screening infants born to mothers with positive syphilis serology and to facilitate accurate and timely communication between the teams caring for mother and baby we have developed a birth plan. Procaine penicillin is now an alternative, not preferred treatment, for all stages of syphilis except neurosyphilis, but the length of treatment for this is shortened. Other changes are summarised at the start of the guideline.

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“…2,3 The pathogen is not fully eradicated, allowing the occurrence of secondary and tertiary stages of reactivation in a substantial number of untreated individuals. 3 The local and systemic persistence of the pathogen far beyond the healing of local lesions and establishment of ‘chancre immunity’ has been reported by several investigators 4,5 and confirmed in the rabbit 6 and guinea‐pig models of syphilis (submitted for publication). We have shown that the guinea‐pig is a suitable host for studies of experimental syphilis, 7,8 and delineation of mechanisms of immunity.…”

Section: Introductionmentioning

confidence: 94%

Cytokine gene expression in skin of susceptible guinea‐pig infected with Treponema pallidum

et al. 1998

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Using a semi‐quantitative multiplex reverse transcription–polymerase chain reaction assay, we examined cytokine mRNA expression for interleukin‐1α (IL‐1α), IL‐2, IL‐10, IL‐12p40, tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β (TGF‐β) in skin samples obtained from C4‐deficient (C4D) guinea‐pigs inoculated intradermally with virulent Treponema pallidum (VTP). Controls included unmanipulated animals, guinea‐pigs injected with T. pallidum‐free rabbit inflammatory testicular fluid (ITF) alone, or mixed with heat‐killed organisms (HKTP). The expression of IL‐1α, IL‐12p40, and TNF‐α mRNA [T helper type 1 (Th1)] remained within the normal range in both infected and control animals throughout the experimental period. However, a significant increase (P<0·05) in IL‐10 mRNA (Th2) was found exclusively in the VTP‐inoculated animals from 3 to 30 days post‐infection. Another unique characteristic of the inflammatory response in infected guinea‐pigs was the appearance, between 11 and 30 days post‐inoculation, of a substantial number of eosinophils in addition to infiltrating mononuclear cells. The results showed a local Th2 response which is consistent with an inadequate immune response. This is reflected by the lengthy and incomplete clearance of the pathogen from the local site of entry and the chronic infection of distant organs.

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Persistence of T. pallidum and its significance in penicillin-treated seropositive late syphilis.

Abstract: The observation of T. pallidum-like organisms reported by Collart, Borel, and Durel (1962, a, b, c, 1964) in the lymph nodes of both men and rabbits in seroreactive treated syphilis and the stimulating work of Smith and Israel (1967 a, b, 1968)

Cited by 14 publications

References 8 publications

Rapid Treponema pallidum Clearance from Blood and Ulcer Samples following Single Dose Benzathine Penicillin Treatment of Early Syphilis

Rapid Treponema pallidum Clearance from Blood and Ulcer Samples following Single Dose Benzathine Penicillin Treatment of Early Syphilis

UK national guidelines on the management of syphilis 2015

Cytokine gene expression in skin of susceptible guinea‐pig infected with Treponema pallidum

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