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  • 1
    Language: English
    In: The Journal of clinical investigation, December 2011, Vol.121(12), pp.4584-92
    Description: 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.
    Keywords: Syphilis -- Prevention & Control
    ISSN: 00219738
    E-ISSN: 1558-8238
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  • 2
    Language: English
    In: Vaccine, March 20, 2014, Vol.32(14), p.1602(8)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.vaccine.2013.09.053 Byline: Caroline E. Cameron, Sheila A. Lukehart Abstract: acents Continuing high incidence rates in developing countries, re-emergent disease in developed nations. acents Failure of decades of public health efforts to control syphilis highlights the need for an effective, inexpensive vaccine. acents Caused by Treponema pallidum; invasive, crosses placental/blood-brain barriers, increases HIV transmission/acquisition. acents Proof-of-principle; [gamma]-irradiated T. pallidum immunization protective, opsonising antibodies/Th1 immune response important. acents Urgent needs; new investigator recruitment, basic research support, study of protection correlates, adjuvant optimization. Author Affiliation: (a) Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada (b) Departments of Medicine and Global Health, University of Washington, Seattle, WA, USA Article History: Received 24 May 2013; Revised 13 September 2013; Accepted 24 September 2013
    Keywords: Vaccines ; Syphilis ; Developing Countries ; Public Health
    ISSN: 0264-410X
    Source: Cengage Learning, Inc.
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  • 3
    Language: English
    In: Journal of Bacteriology, August, 2012, Vol.194(15-16), p.4208(18)
    Description: Although the three Treponema pallidum subspecies (T. pallidum subsp. pallidum, T. pallidum subsp. pertenue, and T. pallidum subsp. endemicum), Treponema paraluiscuniculi, and the unclassified Fribourg-Blanc treponeme cause clinically distinct diseases, these pathogens are genetically and antigenically highly related and are able to cause persistent infection. Recent evidence suggests that the putative surface-exposed variable antigen TprK plays an important role in both treponemal immune evasion and persistence. tprK heterogeneity is generated by nonreciprocal gene conversion between the tprK expression site and donor sites. Although each of the above-mentioned species and subspecies has a functional tprK antigenic variation system, it is still unclear why the level of expression and the rate at which tprK diversifies during infection can differ significantly among isolates. To identify genomic differences that might affect the generation and expression of TprK variants among these pathogens, we performed comparative sequence analysis of the donor sites, as well as the tprK expression sites, among eight T. pallidum subsp. pallidum isolates (Nichols Gen, Nichols Sea, Chicago, Sea81-4, Dal-1, Street14, UW104, and UW126), three T. pallidum subsp. pertenue isolates (Gauthier, CDC2, and Samoa D), one T. pallidum subsp. endemicum isolate (Iraq B), the unclassified Fribourg-Blanc isolate, and the Cuniculi A strain of T. paraluiscuniculi. Synteny and sequence conservation, as well as deletions and insertions, were found in the regions harboring the donor sites. These data suggest that the tprK recombination system is harbored within dynamic genomic regions and that genomic differences might be an important key to explain discrepancies in generation and expression of tprK variants among these Treponema isolates.
    Keywords: Bacterial Genetics -- Research ; Gene Expression -- Research ; Genetic Variation -- Research ; Treponema Pallidum -- Genetic Aspects
    ISSN: 0021-9193
    Source: Cengage Learning, Inc.
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  • 4
    Article
    Article
    Language: English
    In: mBio, 01 July 2018, Vol.9(4), p.e01417-18
    Description: Syphilis research has been severely limited by the necessity to propagate Treponema pallidumin vivo in rabbits. After decades of erroneous or irreproducible reports of cultivation of T. pallidum, the recent very convincing report of its successful long-term in vitro propagation opens numerous opportunities for development of genetic tools for studying pathogenesis and protein function, antigenic variation, and surface exposure of antigens.Syphilis research has been severely limited by the necessity to propagate Treponema pallidumin vivo in rabbits. After decades of erroneous or irreproducible reports of cultivation of T. pallidum, the recent very convincing report of its successful long-term in vitro propagation opens numerous opportunities for development of genetic tools for studying pathogenesis and protein function, antigenic variation, and surface exposure of antigens. The possibility of more rapid isolation of new strains will expand our knowledge of this organism beyond the century-old Nichols strain.
    Keywords: Infectious Disease ; Sexually Transmitted Diseases ; Syphilis ; Biology
    E-ISSN: 2150-7511
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  • 5
    In: The Journal of Infectious Diseases, 2016, Vol. 213(8), pp.1348-1354
    Description: Background.  Human immunodeficiency virus (HIV)–infected individuals may have poorer serological responses to syphilis treatment and may be more likely to experience neurosyphilis. Treponema pallidum is cleared from sites of infection by opsonization, ingestion, and killing by macrophages. Methods.  Serum samples from 235 individuals with syphilis were tested for T. pallidum –specific opsonic activity. Blood T. pallidum concentrations were determined by real-time polymerase chain reaction amplification of the tp0574 gene, and T. pallidum was detected in cerebrospinal fluid (CSF) by reverse-transcriptase polymerase chain reaction of 16S ribosomal RNA. Results.  Opsonic activity was higher with higher serum rapid plasma reagin titers ( P 〈 .001), and in those treated for uncomplicated syphilis before serum collection ( P 〈 .001). Opsonic activity was lower in HIV-infected than in HIV-uninfected individuals even after the above factors were taken into account ( P = .006). In participants in whom blood T. pallidum was detectable, those with the highest opsonic activity had lower blood T. pallidum concentrations. In multivariable analyses, there was not a significant relationship between opsonic activity and detection of T. pallidum in CSF or CSF-VDRL reactivity. Conclusions.  Serum T. pallidum –specific opsonic activity is significantly lower in HIV-infected individuals. Impaired T. pallidum –specific immune responses could contribute to differences in the course of disease or treatment response.
    Keywords: Syphilis ; Immune Response ; Opsonic Antibody ; Neuroinvasion ; Neurosyphilis
    ISSN: 0022-1899
    E-ISSN: 1537-6613
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  • 6
    Language: English
    In: Journal of Infectious Diseases, April 15, 2016, Vol.213(8), p.1348(7)
    Keywords: Syphilis – Care and Treatment ; HIV Infections – Influence ; Treponema Pallidum – Research ; Ribosomal RNA – Research
    ISSN: 0022-1899
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  • 7
    Language: English
    In: Infection and immunity, December 2014, Vol.82(12), pp.4959-67
    Description: Although primary syphilis lesions heal spontaneously, the infection is chronic, with subsequent clinical stages. Healing of the primary chancre occurs as antibodies against outer membrane antigens facilitate opsonophagocytosis of the bacteria by activated macrophages. TprK is an outer membrane protein that undergoes antigenic variation at 7 variable regions, and variants are selected by immune pressure. We hypothesized that individual TprK variants escape immune clearance and seed new disseminated lesions to cause secondary syphilis. As in human syphilis, infected rabbits may develop disseminated secondary skin lesions. This study explores the nature of secondary syphilis, specifically, the contribution of antigenic variation to the development of secondary lesions. Our data from the rabbit model show that the odds of secondary lesions containing predominately TprK variant treponemes is 3.3 times higher than the odds of finding TprK variants in disseminated primary lesions (odds ratio [OR] = 3.3 [95% confidence interval {CI}, 0.98 to 11.0]; P = 0.055) and that 96% of TprK variant secondary lesions are likely seeded by single treponemes. Analysis of antibody responses demonstrates significantly higher antibody titers to tprK variable region sequences found in the inoculum compared to reactivity to tprK variant sequences found in newly arising secondary lesions. This suggests that tprK variants escape the initial immune response raised against the V regions expressed in the inoculum. These data further support a role for TprK in immune evasion and suggest that the ability of TprK variants to persist despite a robust immune response is instrumental in the development of later stages of syphilis.
    Keywords: Antigenic Variation ; Bacterial Proteins -- Immunology ; Porins -- Immunology ; Syphilis -- Immunology ; Treponema Pallidum -- Immunology
    ISSN: 00199567
    E-ISSN: 1098-5522
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  • 8
    In: The New England Journal of Medicine, 2015, Vol.372(8), pp.703-710
    Description: Background Mass treatment with azithromycin is a central component of the new World Health Organization (WHO) strategy to eradicate yaws. Empirical data on the effectiveness of the strategy are required as a prerequisite for worldwide implementation of the plan. Methods We performed repeated clinical surveys for active yaws, serologic surveys for latent yaws, and molecular analyses to determine the cause of skin ulcers and identify macrolide-resistant mutations before and 6 and 12 months after mass treatment with azithromycin on a Papua New Guinean island on which yaws was endemic. Primary-outcome indicators were the prevalence of serologically confirmed active infectious yaws in the entire population and the prevalence of latent yaws with high-titer seroreactivity in a subgroup of children 1 to 15 years of age. Results At baseline, 13,302 of 16,092 residents (82.7%) received one oral dose of azithromycin. The prevalence of active infectious yaws was reduced from 2.4% before mass treatment to 0.3% at 12 months (difference, 2.1 percentage points; P〈0.001). The prevalence of high-titer latent yaws among children was reduced from 18.3% to 6.5% (difference, 11.8 percentage points; P〈0.001) with a near-absence of high-titer seroreactivity in children 1 to 5 years of age. Adverse events identified within 1 week after administration of the medication occurred in approximately 17% of the participants, included nausea, diarrhea, and vomiting, and were mild in severity. No evidence of emergence of resistance to macrolides against Treponema pallidum subspecies pertenue was seen. Conclusions The prevalence of active and latent yaws infection fell rapidly and substantially 12 months after high-coverage mass treatment with azithromycin, with the reduction perhaps aided by subsequent activities to identify and treat new cases of yaws. Our results support the WHO strategy for the eradication of yaws. (Funded by Newcrest Mining and International SOS; YESA-13 ClinicalTrials.gov number, NCT01955252 .) Yaws, an infectious disease caused by Treponema pallidum subspecies pertenue, is endemic in many parts of the world. A community-wide treatment program in Papua New Guinea, in which a single dose of azithromycin was administered, showed substantial disease control. Yaws, an infectious disease caused by Treponema pallidum subspecies pertenue, affects mainly children in poor rural communities in tropical countries. This bacterium is transmitted by direct skin-to-skin, nonsexual contact and causes a chronic, relapsing disease that is characterized by highly contagious primary and secondary cutaneous lesions and by noncontagious tertiary destructive lesions of the bones.1 Cases are reported currently in 12 countries in Africa, Asia, and the western Pacific region, and 42 million people are estimated to be at risk for yaws.2 A major campaign in the 1950s and 1960s to eradicate yaws by means of community-wide treatment with long-acting, . . .
    Keywords: Medicine;
    ISSN: 0028-4793
    E-ISSN: 1533-4406
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  • 9
    Language: English
    In: Journal of Bacteriology, May, 2010, Vol.192(9-10), p.2645(2)
    Description: In syphilis research, the Nichols strain of Treponema pallidum, isolated in 1912, has been the most widely studied. Recently, important differences among T. pallidum strains emerged; therefore, we sequenced and annotated the Chicago strain genome to facilitate and encourage the use of this strain in studying the pathogenesis of syphilis. doi: 10.1128/JB.00159-10
    Keywords: Treponema Pallidum -- Genetic Aspects ; Syphilis -- Research ; Bacterial Genetics -- Research
    ISSN: 0021-9193
    E-ISSN: 10985530
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  • 10
    In: Clinical Infectious Diseases, 2017, Vol. 65(6), pp.943-948
    Description: Compared to those without cognitive impairment, HIV-infected individuals with syphilis who were cognitively impaired had higher CSF concentrations of mediators associated with HIV-related cognitive impairment.
    Keywords: Hiv ; Syphilis ; Neurosyphilis ; Cognitive Impairment ; Inflammation
    ISSN: 1058-4838
    E-ISSN: 1537-6591
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