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PubMed2005

Genome scale identification of Treponema pallidum antigens.

Antibody responses for 882 of the 1,039 proteins in the proteome of Treponema pallidum were examined. Sera collected from infected rabbits were used to systematically identify 106 antigenic proteins, including 22 previously identified antigens and 84 novel antigens. Additionally, sera collected from rabbits throughout the course of infection demonstrated a progression in the breadth and intensity of humoral immunoreactivity against a representative panel of T. pallidum antigens.

Animals↗
PubMed1997

Virulence characteristics of oral treponemes in a murine model.

This study was designed to investigate the virulence characteristics of Treponema denticola, T. socranskii, T. pectinovorum, and T. vincentii following challenge infection of mice. These microorganisms induced well-demarcated, dose-dependent, raised subcutaneous (s.c.) abscesses which were similar in time of onset, lesion progression, and duration of healing. Only viable cells were capable of inducing these characteristic s.c. abscesses. Histological examination of the skin lesion 3 and 5 days postinfection revealed abscess formation in the s.c. tissues, and abundant spiral organisms were demonstrated to be present in the abscess. Host resistance modulation by dexamethasone (neutrophil alteration) and cyclophosphamide (neutrophil depletion) pretreatment had a minimal effect on the virulence expression by any of these treponemes. The T. denticola isolates demonstrated significant trypsin-like protease (TLPase) activity, while both T. socranskii and T. vincentii were devoid of this activity. Interestingly, T. pectinovorum strains were heterogeneous with respect to TLPase as high producers, low producers, and nonproducers. However, no differences in lesion formation were noted regardless of whether the species expressed this proteolytic activity or whether treatment with N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) and dithiothreitol was performed. These results showed that (i) a murine model may be used to evaluate virulence expression by oral treponemes; (ii) while TLPase activity varies among the oral treponemes, this protease does not appear to participate in abscess induction in the mouse model; and (iii) T. pectinovorum strains show variation in TLPase activity.

Animals↗
PubMed2000

The sequence-variable, single-copy tprK gene of Treponema pallidum Nichols strain UNC and Street strain 14 encodes heterogeneous TprK proteins.

Syphilis is a chronic infection with early relapses that are hypothesized to result from the emergence of phenotypic variants of Treponema pallidum. Recent studies demonstrated that TprK, a target of protective immunity, is heterogeneous in several T. pallidum strains, but not in Nichols strain Seattle (A. Centurion-Lara, C. Godornes, C. Castro, W. C. Van Voorhis, and S. A. Lukehart, Infect. Immun. 68:824-831, 2000). Analysis of PCR-amplified tprK from Nichols strain UNC and Street strain 14 treponemes showed that TprK has seven regions of intrastrain heterogeneity resulting from amino acid substitutions, insertions, and deletions. In contrast, analysis of PCR-amplified tprJ showed little intrastrain or interstrain heterogeneity. Reverse transcriptase PCR analysis demonstrated that mRNA transcripts representing unique polymorphic TprK proteins are present during syphilitic infection. Southern hybridization confirmed that Nichols strain UNC and Street strain 14 each contain a single copy of tprK, indicating that intrastrain heterogeneity is due to the presence of multiple treponemal subpopulations which contain a variant form of tprK.

Amino Acid Sequence↗
PubMed2002

Prevalence of blood-borne infectious diseases in blood donors in Ghana.

Transfusion-transmissible infections among 808 blood donors in Ghana were investigated in 1999. Antibody seroprevalences of 3.8, 0.7, 8.4, and 13.5%, respectively, for human immunodeficiency virus, human T-cell lymphotrophic virus type 1, hepatitis C virus (HCV), and Treponema pallidum were obtained. The seroprevalence of HCV infection was confirmed to be 0.9% after supplementary testing, and the transfusion risk potential of these pathogens was demonstrated.

Adolescent↗
PubMed1990

Interaction of human immunodeficiency and papilloma viruses: association with anal epithelial abnormality in homosexual men.

During the 7th annual follow-up of our cohort of homosexual men in 1989, we tested the hypotheses that infection with human immunodeficiency virus (HIV) may enhance the expression of human papilloma virus (HPV) and that the development of anal epithelial abnormality is related to a biologic interaction between these two viruses. Overall, 41 (39%) of the 105 men had anal swabs positive for one or more genotypes of HPV 6/11, 16/18 or 31/33/35. Twenty-three (53%) of the 43 HIV-positive subjects harbored HPV compared to 18 (29%) of the 64 HIV-negative subjects (p = 0.012), including higher prevalence rates for HPV genotypes 16/18 (p = 0.01), 6/11 (p = 0.007), and 31/33/35 (p = 0.07). Multivariate logistic regression analysis of the HIV-positive subjects showed low CD4+ cell counts to be an independent risk factor for detection of HPV (p = 0.04) and in particular for HPV genotypes 31/33/35 (p = 0.02) and 6/11 (p = 0.07). In contrast, similar analysis of the HIV-negative subset showed that a positive antibody test for syphilis was associated with HPV (p = 0.03). Anal epithelial abnormalities were found in 13 (14%) of 92 technically adequate cytologic smears and were strongly associated with detection of any HPV genotypes by the dot-blot method (p = 0.01), and in particular with HPV genotypes 6/11 (p = 0.001). None of 15 subjects with HPV detected only by PCR had anal epithelial abnormality. We propose a viral interaction model, in which HIV-related immune deficiency allows reactivation of HPV, with a subsequent or concomitant appearance of epithelial abnormality.

Anal Canal↗
PubMed1989

Analysis of the humoral immune response to Treponema pallidum in the different stages of untreated human syphilis.

It has been shown that using treponema-specific and lipoidal assays for the demonstration of antibodies to Treponema pallidum subsp. pallidum in pooled sera of syphilitic patients, each stage of the untreated infection can be characterized by a typical immune response as far as specific immunoglobulin M (IgM) and G (IgG) antibody reactivity is concerned. In primary syphilis, IgM antibodies predominate over those of the IgG class. Moreover, IgM antibody reactivity with decreased titres can be detected in the later stages of untreated treponemal infection. Furthermore, it has been shown by using the double antibody radioimmunoprecipitation assay with detergent-solubilized [35S] methionine-labelled Treponema pallidum as antigen followed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and autoradiography, that IgM and IgG antibodies in all stages of infection are directed against eight major antigenic proteins of Treponema pallidum with a Mr of 15,500, 33,000, 34,500, 37,000, 41,000, 44,500, 47,000 and 71,000.

Antibodies, Bacterial↗
PubMed1998

Phylogenetic analysis of cultivable oral treponemes from the Smibert collection.

Dr. Robert Smibert from the Virginia Polytechnic Institute, USA, isolated and collected over 200 strains of oral treponemes over a 20-year period. Dr. Smibert, Dr. W.E.C. Moore and Dr. L.V. Moore separated these isolates and reference strains into different groups on the basis of cellular fatty acid analysis. In this study, the 16S rRNA genes were sequenced for 47 strains that were representative of these groups. Five distinct species were identified on the basis of 16S rRNA sequence comparisons; two of these species are newly named and three have not yet been characterized. The first species, designated Treponema Smibert-1, was represented by the single strain D4B-1 and was later identified as the newly described Treponema maltophilum. However, strain D4B-1 possessed a different flagellar arrangement to that of T. maltophilum. The second species, Treponema Smibert-2, was represented by nine isolates that possessed identical 16S rRNA gene sequences. The closest relatives of this species were Treponema Smibert-3 and Treponema Smibert-4 at approximately 90% sequence similarity. Within Treponema Smibert-2, there was no correlation between phylogenetic analysis and cellular fatty acid analysis since six different cellular fatty acid groups represented the nine strains. Treponema Smibert-3 (strain D36ER-1) and Treponema Smibert-4 (D62CR-12) were each represented by only a single strain and were closely related to each other at 98% sequence similarity. Strain D36ER-1 of Treponema Smibert-3 was identified as belonging to the not-yet-cultivated phylotype 20 [Choi, B.K., Paster, B.J., Dewhirst, F.E. & Göbel, U.B. (1994). Infect Immun 62, 1889-1895]. Strain D62CR-12 of Treponema Smibert-4 was nearly identical in sequence to the newly described Treponema amylovorum. The fifth species, Treponema Smibert-5, was represented by a single strain, D120CR-1, and was closely related at about 98% sequence similarity to the three subspecies of Treponema socranskii. The polygenetic analyses of strains of Treponema vincentii and of subspecies of T. socranskii are also reported. The closest oral relatives of T. vincentii were Treponema medium at 98.7% sequence similarity and Treponema denticola at 91.5% sequence similarity. T. socranskii subspp. socranskii, buccale and paredis formed three separate phylogenetic branches with sequence similarities of about 98% to each other. The closest relative of the subspecies of T. socranskii and of Smibert-5 was Smibert-2 at about 86% sequence similarity. Historic reference strains Fuji, 'Treponema ambigua', Fm, Ichelson-2, N-39, TD2, TRRD, MRB, IPP, Jethro and T32A, as well as an unkown strain designated only as Treponema oralis, were identified as strains of T. denticola. Reference strains Fuji, Jethro, T32A, and IPP plus three isolates of the Smibert collection were also contaminated with a mycoplasma as determined by 16S rRNA comparative analysis. Consequently, spirochaetal cultures should be screened for mycoplasmas. There are presently at least ten species of cultivable oral species of treponema with the cut-off for separate species designation at about 98% sequence similarity. However, DNA-DNA reassociation experiments are necessary to differentiate species when 16S rDNA sequence similarities are at about this level.

DNA, Bacterial↗
PubMed1988

Specificity of antibodies from patients with pinta for antigens of Treponema pallidum subspecies pallidum.

Inhabitants of a remote Panamanian village were examined for clinical and serological evidence of pinta infection. Of 104 persons examined, 21 (20%) had clinical evidence of active or inactive pinta, and 54 (52%) were seropositive. Sera were evaluated for antibody to individual Treponema pallidum antigens. Sera from all four patients with active pinta contained antibody to the 47-48 kilodalton major antigen; the intensity of reactivity and the number of antigens recognized increased with age and, presumably, duration of infection. Sera from six children with inactive pinta reacted strongly with multiple T. pallidum antigens, whereas adults with inactive pinta had less intense reactivity against fewer molecules. Seronegative controls demonstrated only weak reactivity to fewer than five molecules. The development of antibody reactivity to the full spectrum of T. pallidum antigens during the course of infection demonstrates the high degree of antigenic relatedness of T. pallidum and Treponema carateum and is similar to the development of humoral responsiveness during syphilis infection.

Adolescent↗
PubMed1975

Effect of pretreatment with Mycobacterium bovis (strain BCG) and immune syphilitic serum on rabbit resistance to Treponema pallidum.

Stimulation of the rabbit reticuloendothelial system with viable Mycobacterium bovis (strain BCG), and other agents, had no effect on the development of syphilitic lesions after intradermal or intravenous inoculation with graded doses of Treponema pallidum (virulent Nichol's strain; mean infective doses less than 10). The simultaneous administration of immune syphilitic rabbit serum retarded the development of lesions, but this appeared to be due solely to the immune serum, suggesting no synergism between the activated reticuloendothelial system and the anti-T. pallidum antibodies. The administration of two doses of BCG enhanced syphilitic lesion development in the rabbit.

Animals↗
PubMed2001

Evaluation of recomWell Treponema, a novel recombinant antigen-based enzyme-linked immunosorbent assay for the diagnosis of syphilis.

OBJECTIVE: To evaluate the diagnostic performance of an enzyme immunosorbent assay (recomWell Treponema) for the diagnosis of syphilis. The novel recombinant antigens Tpn47, TpN17 and TpN15 were utilized. METHODS: A total of 782 human serum specimens, belonging to four different categories (blood donors, n = 200; routine laboratory screening for syphilis, n = 400; syphilis patients, n = 122; potential cross-reactors, n = 60), were evaluated to compare the sensitivity and specificity of the recomWell Treponema kit with a standard whole Treponema pallidum cell lysate antigen-based ELISA (Syphilis Screening) and with micro-haemagglutination (MHA-TP). RESULTS: The overall specificity and sensitivity of the recomWell Treponema IgG was 98.9% and 98.3%, respectively. The specificity and sensitivity of Syphilis Screening ELISA was 98.7% and 98.3%, respectively. The agreement between recomWell Treponema and Syphilis Screening was 100%, 97.8%, 95.9% and 95% among the blood donor specimens, screening samples, syphilis specimens and the potential cross-reactors, respectively. Values of concordance varying from 96.7% to 98.3% were found in the different groups of sera between recomWell Treponema and MHA-TP. In addition, recomWell Treponema demonstrated a good diagnostic performance when used to detect the IgM to T. pallidum. No false-positive sera were identified and, in 17/19 samples from primary infection, an IgM immune response was found. CONCLUSIONS: recomWell Treponema was shown to be a highly specific and sensitive method in all stages of syphilis screening and it can be considered as alternative to other ELISA tests based on native antigen preparations.

Antibodies, Bacterial↗
PubMed1991

Purulent nasal discharge.

Purulent nasal discharge is a common presenting symptom associated with infections of the upper respiratory tract. The most likely diagnoses are uncomplicated viral upper respiratory infections and bacterial sinusitis. Allergy may be an underlying problem in children with sinusitis. Less common considerations are adenoiditis, infections caused by B. pertussis, C. diphtheriae or Treponema pallidum or intranasal structural problems.

Amoxicillin↗
PubMed1998

Comparison of clinically directed, disease specific, and syndromic protocols for the management of genital ulcer disease in Lesotho.

OBJECTIVE: To evaluate two protocols for the syndromic management of genital ulcer disease (GUD) in Lesotho, southern Africa and to compare the performance of these protocols with that of a conventional disease specific approach. METHODS: A cross sectional study was conducted among consecutive patients with GUD attending an STD clinic in Maseru, Lesotho. The clinical diagnoses were made by using predefined criteria at the initial visit before the performance of laboratory tests. Attempts were made to detect the specific aetiology of the genital ulcers using PCR assays and syphilis serology. The results of PCR assays and syphilis serology were used as the gold standard against which the performance of the management approaches were applied. RESULTS: Of 100 patients initially recruited into the study, Haemophilus ducreyi infection was detected in 56%, herpes simplex virus in 26%, Treponema pallidum in 23%, and lymphogranuloma venereum in 7%. No pathogens were detected in 6% of patients. 17% of patients had mixed infections. Sensitivity, specificity, positive and negative predictive values of the three management protocols for GUD were compared after applying each to the study population. Theoretically, the lowest correct treatment rate would have been obtained by using the disease specific protocol (62%) compared with more than 90% in both syndromic management protocols. Considerable overtreatment for primary syphilis would occur following application of both syndromic protocols. This would be the result of the overdiagnosis of chancroid, in particular the misdiagnosis of genital herpes as chancroid, which would receive treatment for syphilis unnecessarily. The HIV seroprevalence among these patients was 36%. A significantly higher rate of HIV seropositivity was detected among the patients with herpes simplex virus infection when compared with those patients having other causes of genital ulcer disease (58% v 27%; odds ratio 3.73; 95% CI 1.26-11.26; p = 0.01). CONCLUSIONS: Poor sensitivity, specificity, and predictive values were recorded when the disease specific protocol was applied to the study population. In contrast, the syndromic management protocols provided adequate treatment for more than 90% of patients with GUD. Protocol C, which identified a minority of cases of genital herpes, was found to have an advantage when compared with protocol B (all patients with genital ulcer disease treated for both syphilis and chancroid) in that 29% of genital herpes cases would receive appropriate counselling.

Chancroid↗
PubMedDate not supplied

[Neurosyphilis: forms of presentation and clinical management].

INTRODUCTION AND AIMS: Neurosyphilis results from the infection of the central nervous system by Treponema pallidum. It causes diverse clinical pictures which are occasionally similar to other, better known neurological diseases. In this paper our aim is to offer a global clinical vision of this entity by reviewing the different forms it can take and its diagnostic and therapeutic management. DEVELOPMENT: The forms of presentation of neurosyphilis can be grouped in two categories: early (asymptomatic, meningeal and meningovascular neurosyphilis) and late (progressive general paralysis and tabes dorsalis). Other less important forms, such as gummas, ocular forms, syphilitic amyotrophy or hypoacusis, have also been described. Diagnosis is complex and is based on the study of the cerebrospinal fluid. Given the difficulty involved in performing an accurate diagnosis, different criteria have been developed in which T. pallidum serology plays a key role. The most effective treatment is penicillin, although on occasions it may have no effect and we therefore recommend clinical and fluid analysis follow ups. Lastly, we describe the changes in incidence and clinical presentation, and the complications that may arise in diagnosis when HIV carrying patients also suffer from this disease. CONCLUSIONS: Neurosyphilis is a disease that still occurs nowadays and, due to its clinical polymorphism, must be borne in mind as a differential diagnosis in a number of neurological and psychiatric illnesses. This, together with the fact the serological tests are difficult to interpret and its irregular response to the usual treatment, makes it difficult to manage and means that the neurologist must have a thorough knowledge of the disorder.

Anti-Bacterial Agents↗
PubMed1997

Identification of homologs for thioredoxin, peptidyl prolyl cis-trans isomerase, and glycerophosphodiester phosphodiesterase in outer membrane fractions from Treponema pallidum, the syphilis spirochete.

In this study, we characterized candidate rare outer membrane (OM) proteins with apparent molecular masses of 19, 27, 38, and 38.5 kDa, which had been identified previously in OM fractions from Treponema pallidum (J. D. Radolf et al., Infect. Immun. 63:4244-4252, 1995). Using N-terminal and internal amino acid sequences, a probe for the 19-kDa candidate was PCR amplified and used to screen a T. pallidum genomic library in Lambda Zap II. The corresponding gene (tlp) encoded a homolog for periplasmic thioredoxin-like proteins (Tlp), which reduce c-type cytochromes. A degenerate oligonucleotide derived from the N terminus of the 27-kDa protein was used to PCR amplify a duplex probe from a T. pallidum genomic library in pBluescript II SK+. With this probe, the corresponding gene (ppiB) was identified and found to code for a presumptive periplasmic cyclophilin B-type peptidyl prolyl cis-trans isomerase (PpiB). We postulate that PpiB assists the folding of proteins within the T. pallidum periplasmic space. The N terminus of the 38-kDa candidate was blocked to Edman degradation. However, internal sequence data revealed that it was basic membrane protein (Bmp), a previously characterized, signal peptidase I-processed protein. Triton X-114 phase partitioning revealed that despite its name, Bmp is hydrophilic and therefore likely to be periplasmic. The final candidate was also blocked to Edman degradation; as before, a duplex probe was PCR amplified with degenerate primers derived from internal sequences. The corresponding gene (glpQ) coded for a presumptively lipid-modified homolog of glycerophosphodiester phosphodiesterase (GlpQ). Based upon findings with other treponemal lipoproteins, the hydrophilic GlpQ polypeptide is thought to be anchored by N-terminal lipids to the periplasmic leaflet(s) of the cytoplasmic membrane and/or OM. The discovery of T. pallidum periplasmic proteins with potentially defined functions provides fresh insights into a poorly understood aspect of treponemal physiology. At the same time, however, these findings also raise important issues regarding the use of OM preparations for identifying rare OM proteins of T. pallidum.

Amino Acid Sequence↗
PubMed1983

[Treponema pallidium IgM enzyme-linked immunosorbent assay (TP-IgM-ELISA). Determination of organism-specific Treponema IgM antibodies in the serum of syphilis patients with and without central nervous system involvement of the infection].

For demonstration of treponemal IgM antibodies in sera and CSF taken from 56 syphilitic patients with or without involvement of the CNS in the infection, comparative studies have been performed making use of the 19S(IgM)-FTA-ABS test and a TP-IgM-ELISA. Compared with the 19S(IgM)-FTA-ABS, the TP-IgM-ELISA has a specificity of 97% and a sensitivity of 93%. With regard to qualitative investigation of serum samples, both tests showed nearly equivalent results. In 10 out of 16 CSF samples taken from patients with untreated neurosyphilis, a treponemal IgM antibody could be proved by TP-IgM-ELISA. According to these findings, this assay seems to be a reliable test system for demonstration of treponemal IgM antibodies not only in serum but also in CSF.

Antibodies, Bacterial↗
PubMed1992

Treponemal infection and the outcome of pregnancy in a rural area of The Gambia, west Africa.

Of 826 pregnant women studied in a rural area of The Gambia, 77 (9.3%) were seropositive for a treponemal infection (positive rapid plasma reagin [RPR] and Treponema pallidum hemagglutination [TPHA] test). The perinatal death rate recorded prospectively in babies of 77 seropositive women (39.0/1000 births) was less than that among babies of 720 seronegative women (77.6/1000 births; odds ratio, 0.48; 95% confidence interval, 0.15-1.57). No increase in mortality or morbidity was found among the children of 39 seropositive women compared with the children of 39 control women. Seropositivity was found in only 20 (1.1%) of 1872 children less than 14 years old residing in the same community. The finding that the babies of rural Gambian women seropositive for syphilis are not at risk of early death is of importance in determining the priority that should be given to establishing antenatal screening programs in The Gambia and neighboring communities.

Adolescent↗
PubMedDate not supplied

Sexually transmitted diseases and pregnancy.

The association of adverse pregnancy outcome with Treponema pallidum, Neisseria gonorrhoeae and herpes simplex infections is well known and specific recommendations for management have been formulated. However, other agents that are not so well known can be transmitted sexually and threaten an otherwise healthy pregnancy. These agents are discussed in order to make the nurse more aware of related maternal and fetal diseases.

Chlamydia Infections↗