<i>Treponema pallidum</i>Strain‐Specific Differences in Neuroinvasion and Clinical Phenotype in a Rabbit Model

Tantalo, Lauren C.; Lukehart, Sheila A.; Marra, Christina M.

doi:10.1086/426510

Cited by 77 publications

(46 citation statements)

References 14 publications

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“…The absence of T. pallidum DNA in 60% of the brains at this time point insinuates that the Nichols strain is not as neuroinvasive as previously thought. This finding is in agreement with a previous study by Tantalo et al (33) showing that the Nichols strain was present in the brain of only 2/8 rabbits studied and monitored over a 3-month period and, when present, was rapidly cleared. The lower DNA copy numbers in the organs studied, in contrast to the very high numbers in whole blood or plasma, suggest that replication in these tissues begins at a later point and perhaps in lower numbers following bacteremic spread from the infected testes.…”

Section: Discussionsupporting

confidence: 93%

Assessment of the Kinetics ofTreponema pallidumDissemination into Blood and Tissues in Experimental Syphilis by Real-Time Quantitative PCR

et al. 2007

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Little is known about the size and kinetics of treponemal burdens in blood and tissues during acquired or experimental syphilitic infection. We used real-time quantitative PCR to measure Treponema pallidum DNA levels in rabbits infected intratesticularly with the prototype Nichols strain. At the outset, we performed a series of in vitro blood spiking experiments to determine the effect of blood processing procedures on the distribution of treponemes in various blood components. T. pallidum DNA levels in plasma and whole blood were approximately 10-fold higher than those in serum and more than 200-fold greater than those in peripheral blood mononuclear cells (PBMCs). Ten rabbits were inoculated intratesticularly with doses of treponemes ranging from 4 ؋ 10 7 to 2 ؋ 10 8 organisms. In five rabbits, T. pallidum DNA levels were measured sequentially in serum, plasma, whole blood, and PBMCs until sacrifice at peak orchitis, at which time brain, kidney, liver, spleen, and testicles were harvested; blood and organs were also harvested at orchitis from the other five rabbits. T. pallidum DNA was detected in plasma within 24 h postinfection. Treponeme levels in whole blood and blood components increased significantly with the development of peak orchitis. Overall, levels in serum and PBMCs were lower than those in plasma and whole blood; this disparity was particularly marked at early time points. Significantly greater numbers of spirochetes were found in the spleen than in liver, kidney, or brain tissue at the time of sacrifice. Our findings highlight the remarkable capacity of T. pallidum to disseminate from the site of infection to blood and tissues, and they identify the spleen as a prime target for treponemal invasion.

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Section: Discussionsupporting

confidence: 93%

Assessment of the Kinetics ofTreponema pallidumDissemination into Blood and Tissues in Experimental Syphilis by Real-Time Quantitative PCR

et al. 2007

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“…Investigators believed that the course of events after neuroinvasion was, at least in part, determined by the host response to infection. For example, several investigators noted a correlation between the severity of the secondary syphilis skin rash and identification of CSF abnormalities in early syphilis [51]. Merritt et al [19] noted that symptomatic NS was rarely seen in individuals who had experienced severe skin manifestations.…”

Section: Discussionmentioning

confidence: 99%

Clinical Spectrum of Neurosyphilis among HIV-Negative Patients in the Modern Era

et al. 2013

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Background: The clinical spectrum of neurosyphilis (NS) has changed over time. Objective: To describe the clinical spectrum and characteristics of NS in HIV-negative patients. Methods: A retrospective chart review was performed for 149 in patients with NS. Result: All patients were >25 years old, including 16.8% asymptomatic for NS, 15.4% with syphilitic meningitis, 24.2% with meningovascular NS, 38.9% with general paresis, 4.0% with tabes dorsalis and 0.7% with gummatous NS. The original misdiagnosis rate was 84.6%. All 149 patients had positive serum Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR). The overall positive rates of cerebrospinal fluid RPR (CSF-RPR) and CSF-TPPA were 57.0 and 89.9%, respectively. CSF pleocytosis and elevated CSF protein were found in 40.3% of patients. Nonspecific abnormal brain magnetic resonance imaging and electroencephalography findings were present in 60.4 and 54.8% of NS patients, respectively. Conclusions: NS has various clinical manifestations, laboratory findings and magnetic resonance imaging and electroencephalography findings, but all studies lack specificity. Every patient with neurological or psychiatric symptoms that are without unambiguous causes should have blood tests for syphilis. When serology proves positive, patients should undergo CSF examination.

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“…Clinical descriptions from the pre-antibiotic era (137) and studies in the rabbit infection model suggest that some strains are more prone to neuroinvasion (138). A recent study of T. pallidum showed that patients infected with strain type 14d/f had a higher rate of neurosyphilis compared with patients infected with other strain types (135).…”

Section: Molecular Strain Typing Of T Pallidummentioning

confidence: 99%

Syphilis: using modern approaches to understand an old disease

Lukehart²

2011

J. Clin. Invest.

202

168

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Syphilis is a fascinating and perplexing infection, with protean clinical manifestations and both diagnostic and management ambiguities. Treponema pallidum subsp. pallidum, the agent of syphilis, is challenging to study in part because it cannot be cultured or genetically manipulated. Here, we review recent progress in the application of modern molecular techniques to understanding the biological basis of this multistage disease and to the development of new tools for diagnosis, for predicting efficacy of treatment with alternative antibiotics, and for studying the transmission of infection through population networks.

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Treponema pallidumStrain‐Specific Differences in Neuroinvasion and Clinical Phenotype in a Rabbit Model

Abstract: There are particularly neuroinvasive T. pallidum strains, and the clinical phenotype of infection varies with infecting strain. This information could ultimately be used to identify patients at increased risk for neuroinvasion and, thus, at risk for neurosyphilis.

Cited by 77 publications

References 14 publications

Assessment of the Kinetics ofTreponema pallidumDissemination into Blood and Tissues in Experimental Syphilis by Real-Time Quantitative PCR

Assessment of the Kinetics ofTreponema pallidumDissemination into Blood and Tissues in Experimental Syphilis by Real-Time Quantitative PCR

Clinical Spectrum of Neurosyphilis among HIV-Negative Patients in the Modern Era

Syphilis: using modern approaches to understand an old disease

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