Relapse of Secondary Syphilis After Benzathine Penicillin G

Myint, Michael; Bashiri, Houman; Harrington, Robert D.; Marra, Christina M.

doi:10.1097/01.olq.0000114941.37942.4c

Cited by 35 publications

(26 citation statements)

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“…Possible reasons for this discrepancy (associated with tpr restriction pattern) may be related to (i) the existence of other sexual partners, (ii) the presence of a mixed infection, and (iii) genetic variation of the tpr gene subfamily II during host passage that results in different restriction patterns. This last hypothesis is supported by the findings of several other studies (2,7,12) that provided evidence of tprK sequence diversification during T. pallidum infection and host transmission. As recommended by Pillay et al (14) and reinforced by our results, further studies will be necessary to evaluate the stability of the T. pallidum tpr subtypes within individual sexual networks.…”

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confidence: 78%

Molecular Typing of Treponema pallidum Clinical Strains from Lisbon, Portugal

et al. 2008

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A molecular system was used to subtype Portuguese Treponema pallidum clinical strains isolated from both skin lesions and blood. The study with this system constitutes the first typing study in a European country. Three T. pallidum subtypes were found: subtypes 14a (50%), 14d (45.2%), and 14f (4.8%). Further studies are needed to better characterize the isolates involved in syphilis outbreaks.Syphilis, caused by the spirochete Treponema pallidum subsp. pallidum, is a multistage disease with a wide spectrum of clinical manifestations (8). Of particular relevance to public health is the recognition that syphilis increases the risk of transmission and acquisition of the human immunodeficiency virus (6). Until the end of the 20th century, the in vitro noncultivable condition of T. pallidum, allied with the high GC content of major portions of its genome (5), prevented the success of any strategy for the typing of T. pallidum clinical isolates. In 1998, Pillay et al. (13) made a very important step toward obtaining an understanding of the molecular epidemiology of T. pallidum by developing the only existing method for the genotyping of this pathogen. The method is based on the intrastrain variability of the acidic repeat protein gene (arp) and the Treponema pallidum repeat gene (tpr). To date, the laboriousness and low sensitivity of this procedure have limited its application to only five published studies (11,(13)(14)(15)17), focused mainly in two countries, South Africa and the United States. Consequently, there are only 288 typed T. pallidum strains worldwide (11,(13)(14)(15)17), which is a strikingly small number, considering the predicted syphilis incidence rate (18). In Portugal, early and congenital syphilis require mandatory notification (4); nonetheless, as in the rest of Europe, there is a complete lack of awareness of the diversity of the circulating T. pallidum strains. Here we report the results of a pioneer study in which we used the recent subtyping system developed by Pillay et al. at the Centers for Disease Control and Prevention (13) in order to identify and differentiate Portuguese T. pallidum isolates.Four hundred sixteen individuals (104 women and 312 men) suspected of having early syphilis (on the basis of clinical data and serology), most of whom were attending the major Portuguese sexually transmitted disease clinic (located at the Lapa Health Centre in Lisbon, Portugal), were evaluated for T. pallidum infection between 2004 and 2007. T. pallidum DNA was extracted from skin lesions or blood samples by using a QIAamp DNA mini kit (Qiagen, Valencia, CA), according to the manufacturer's instructions. T. pallidum was detected in 86 specimens (35 primary and 7 secondary lesions and 44 blood samples) by using a commercially available real-time PCR assay (Sacace, Caserta, Italy) that targets the gene coding for a recognized T. pallidum surface antigen, the 39-kDa basic membrane protein (bmp; locus TP1016 relative to the sequence of T. pallidum strain Nichols, GenBank accession number NC_000919 [3,5]...

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Molecular Typing of Treponema pallidum Clinical Strains from Lisbon, Portugal

et al. 2008

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“…The genes of T. pallidum bacteria are heterogeneous within and among T. pallidum strains [41,42]. A possibility to distinguish relapse from re-infection can be achieved by comparing the genes of T. pallidum that were isolated from the blood and the CSF of the initial and the control examinations.…”

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confidence: 99%

Late-stage neurosyphilis presenting with severe neuropsychiatric deficits: diagnosis, therapy, and course of three patients

et al. 2011

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Neurosyphilis is an infectious disease that has reappeared over the past two decades. It is caused by Treponema pallidum subspecies pallidum that can affect the central nervous system (CNS) during any stage of the disease. Besides early CNS involvement predominantly presenting with symptoms of meningitis, a parenchymal affection of the brain leading to severe neuropsychiatric symptoms particularly emerges at later stages, but is rarely seen nowadays due to early antibiotic treatment. Together with the clinical findings, a characteristic combination of serological and cerebrospinal fluid (CSF) abnormalities leads to the diagnosis of neurosyphilis and is required to assess its activity. However, particularly at later stages of disease and after antibiotic treatment, serological and CSF abnormalities may become ambiguous and, therefore, difficult to interpret. This can be accompanied by persisting or fluctuating neuropsychological deficits. To this day, no well-controlled clinical data exists concerning the treatment of late-stage neurosyphilis, neither on type, optimal dosage, duration, and long-term efficacy of antibiotic therapy. Therefore, treatment and follow-up of late-stage neurosyphilis are challenging tasks. Here, we present three cases of neurosyphilis with severe neuropsychiatric symptoms in non-immunocompromised patients and a review of the recent literature.

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“…The heterogeneity observed in the seven variable regions of tprK arises during rabbit passage (57, 163); diversity is also seen in tprK sequenced directly from patients with primary and secondary syphilis (163,215). Some of the other tpr genes have also displayed variation, although the diversity is of a different type.…”

Section: Genetic Variation Among Subspecies and Strains Tpr Genesmentioning

confidence: 99%

Biological Basis for Syphilis

2006

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SUMMARY Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subsp. pallidum. Clinical manifestations separate the disease into stages; late stages of disease are now uncommon compared to the preantibiotic era. T. pallidum has an unusually small genome and lacks genes that encode many metabolic functions and classical virulence factors. The organism is extremely sensitive to environmental conditions and has not been continuously cultivated in vitro. Nonetheless, T. pallidum is highly infectious and survives for decades in the untreated host. Early syphilis lesions result from the host's immune response to the treponemes. Bacterial clearance and resolution of early lesions results from a delayed hypersensitivity response, although some organisms escape to cause persistent infection. One factor contributing to T. pallidum's chronicity is the paucity of integral outer membrane proteins, rendering intact organisms virtually invisible to the immune system. Antigenic variation of TprK, a putative surface-exposed protein, is likely to contribute to immune evasion. T. pallidum remains exquisitely sensitive to penicillin, but macrolide resistance has recently been identified in a number of geographic regions. The development of a syphilis vaccine, thus far elusive, would have a significant positive impact on global health.

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Relapse of Secondary Syphilis After Benzathine Penicillin G

Abstract: Our patient likely relapsed despite treatment.

Cited by 35 publications

References 9 publications

Molecular Typing of Treponema pallidum Clinical Strains from Lisbon, Portugal

Molecular Typing of Treponema pallidum Clinical Strains from Lisbon, Portugal

Late-stage neurosyphilis presenting with severe neuropsychiatric deficits: diagnosis, therapy, and course of three patients

Biological Basis for Syphilis

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