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PubMed2000

A novel polymorphism in the toll-like receptor 2 gene and its potential association with staphylococcal infection.

The toll-like receptor 2 (TLR2) has gained importance as a major mammalian receptor for lipoproteins derived from the cell wall of a variety of bacteria, such as Borrelia burgdorferi, Treponema pallidum, and Mycoplasma fermentans. We were interested in identifying mutations in the TLR2 gene that might prove to be associated with altered susceptibility to septic shock. We performed a mutation screen of the TLR2 gene using single-stranded conformational polymorphism in 110 normal, healthy study subjects and detected an Arg753Gln mutation in three individuals. No other missense mutations were detected in the TLR2 open reading frame. Functional studies demonstrate that the Arg753Gln polymorphism, in comparison to the wild-type TLR2 gene, is significantly less responsive to bacterial peptides derived from B. burgdorferi and T. pallidum. In a septic shock population, the Arg753Gln TLR2 polymorphism occurred in 2 out of 91 septic patients. More importantly, both of the subjects with the TLR2 Arg753Gln polymorphism had staphylococcal infections. These findings suggest that a mutation in the TLR2 gene may predispose individuals to life-threatening bacterial infections.

Amino Acid Sequence↗
PubMed2000

The tprK gene is heterogeneous among Treponema pallidum strains and has multiple alleles.

We have previously shown that the TprK antigen of T. pallidum, Nichols strain, is predominantly expressed in treponemes obtained 10 days after infection and that the hydrophilic domain of TprK is a target of opsonic antibodies and confers significant protection against homologous challenge. The T. pallidum genome sequence reported the presence of a single copy of the tprK gene in the Nichols strain. In the present study we demonstrate size heterogeneity in the central portions of the TprK hydrophilic domains of 14 treponemal isolates. Sequence analysis of the central domains and the complete open reading frames (ORFs) of the tprK genes confirms this heterogeneity. Further, multiple tprK sequences were found in the Nichols-defined tprK locus in three isolates (Sea 81-4, Bal 7, and Bal 73-1). In contrast, only a single tprK sequence could be identified in this locus in the Nichols strain. Alignment of the DNA and deduced amino acid sequences of the whole tprK ORFs shows the presence of seven discrete variable domains flanked by highly conserved regions. We hypothesize that these heterogeneous regions may be involved in antigenic heterogeneity and, in particular, evasion of the immune response. The presence of different tprK alleles in the tprK locus strongly suggests the existence of genetically different subpopulations within treponemal isolates.

Alleles↗
PubMed1985

Interactions of fibronectin with Treponema pallidum.

The adhesive or opsonic glycoprotein, fibronectin, is associated with the surface of Treponema pallidum as shown by immunofluorescence. A quantitative assay using iodine-125 (125I) showed that T pallidum harvested seven days after infection bound more fibronectin than T pallidum harvested 14 days after infection. This increased binding by "younger" organisms was confirmed by radioimmunoassay techniques. Fibronectin appears to have a role in treponemal attachment. Preincubation of T pallidum with goat or rabbit antibody to fibronectin blocked treponemal attachment to cultured cells and to isolated capillaries and inhibited treponemal virulence. Treponemes were incubated in glass wool columns pretreated with fibronectin and were then eluted from the columns. This technique yielded a population of T pallidum that failed to bind to fibronectin. Compared with treponemes eluted from control ovalbumin columns, organisms eluted from fibronectin columns attached to cultured cells in larger numbers but did not survive as long and were not as virulent. Findings are discussed in terms of the relevance of interaction between treponemes and fibronectin in the pathogenesis of T pallidum.

Animals↗
PubMedDate not supplied

[Characteristics related to STD/HIV in men working in Mexico City bars where female prostitution takes place].

OBJECTIVE: This research work intended to describe the characteristics and the seroprevalence of some sexually transmitted diseases (STD), in men working in bars where female commercial sex takes place. MATERIAL AND METHODS: The study included an evaluation of 171 males during 1993, who were employed in bars and who were potentially at risk of contact with female commercial sex workers (FCSW). A structured survey was conducted in order to collect information about social, demographic and sexual behavior characteristics. Blood samples were also obtained to test for antibodies against Treponema pallidum (RPR/FTA-ABS), human immunodeficiency virus (VIH) (ELISA, Western blot), Herpes simplex virus type-2 (HSV-2) (Western blot) and the core antigen of hepatitis B virus (HBV) (ELISA). RESULTS: Test results showed low infection rates of HIV, T: pallidum and HBV: 0%, 2.4% and 1.8%, respectively. However, their HSV-2 infection proportion (32.4%) was considered intermediate in comparison to the prevalence of FCSW from bars (55.5%), to that found in heterosexual men (14.6%), and to proportions found in women general population (29.3% and 17.9%). CONCLUSIONS: The men's age and a history of sexual intercourse with FCSW were strong predictors of HSV-2 infection. These findings evidence a relationship between men working in bars and FCSW in terms of STD transmission and show the need for preventive care directed to this group.

Adolescent↗
PubMed1999

Genital ulcers: etiology, clinical diagnosis, and associated human immunodeficiency virus infection in Kingston, Jamaica.

Individuals presenting consecutively with genital ulcers in Kingston, Jamaica, underwent serological testing for human immunodeficiency virus (HIV) infection, chlamydial infection, and syphilis. Ulcer material was analyzed by multiplex polymerase chain reaction (M-PCR) analysis. DNA from herpes simplex virus (HSV), Haemophilus ducreyi, and Treponema pallidum was detected in 158 (52.0%), 72 (23.7%), and 31 (10.2%) of 304 ulcer specimens. Of the 304 subjects, 67 (22%) were HIV-seropositive and 64 (21%) were T. pallidum-seroreactive. Granuloma inguinale was clinically diagnosed in nine (13.4%) of 67 ulcers negative by M-PCR analysis and in 12 (5.1%) of 237 ulcers positive by M-PCR analysis (P = .03). Lymphogranuloma venereum was clinically diagnosed in eight patients. Compared with M-PCR analysis, the sensitivity and specificity of a clinical diagnosis of syphilis, herpes, and chancroid were 67.7%, 53.8%, and 75% and 91.2%, 83.6%, and 75.4%, respectively. Reactive syphilis serology was 74% sensitive and 85% specific compared with M-PCR analysis. Reported contact with a prostitute in the preceding 3 months was associated with chancroid (P = .009), reactive syphilis serology (P = .011), and HIV infection (P = .007). The relatively poor accuracy of clinical and locally available laboratory diagnoses pleads for syndromic management of genital ulcers in Jamaica. Prevention efforts should be intensified.

Adult↗
PubMed1999

Antibody to herpes simplex virus type 2 as a marker of sexual risk behavior in rural Tanzania.

A serosurvey was conducted in a random sample of 259 women and 231 men in 12 rural communities in Mwanza Region, Tanzania, using a type-specific ELISA for Herpes simplex virus type 2 (HSV-2) infection. Seroprevalence rose steeply with age to approximately 75% in women >=25 years old and 60% in men >=30. After adjusting for age and residence, HSV-2 prevalence was higher in women who were married, in a polygamous marriage, Treponema pallidum hemagglutination assay (TPHA)-positive, had more lifetime sex partners, or who had not traveled. Prevalence was higher in men who were married, had lived elsewhere, had more lifetime partners, had used condoms, or were TPHA-positive. HSV-2 infection was significantly associated with recent history of genital ulcer. The association between HSV-2 infection and lifetime sex partners was strongest in those <25 years old in both sexes. This association supports the use of HSV-2 serology as a marker of risk behavior in this population, particularly among young people.

Adolescent↗
PubMed2006

Application of a noninvasive oral fluid test for detection of treponemal IgG in a predominantly HIV-infected population.

The performance of a time-resolved fluorescence immunoassay (TRFIA) for detection of treponemal IgG from oral fluid specimens has been assessed in a predominantly HIV-infected population. Serological investigation is the method of choice for confirming clinical suspicion of syphilis; however, in the primary stage of disease, direct detection of treponemes in lesion fluid or Treponema pallidum DNA is recommended because of the reduced sensitivity of serological tests. There may be occasions when blood for serological investigation is difficult to obtain due to individual patient preference or logistical necessity to improve participation in screening initiatives, particularly in outreach situations. Collection of oral fluid for detection of treponemal antibody may prove an attractive alternative and, with this in mind, an oral fluid assay for detection of treponemal IgG was developed. Time-resolved fluorescence was used to detect treponemal IgG extracted from commercially available oral fluid collection devices. Paired serum and saliva samples were obtained from 210 individuals, 101 of whom were diagnosed with syphilis on the grounds of medical examination confirmed by serological testing. Oral fluid specimens from 14 subjects were rejected because they contained insufficient control antibody or were inhibitory. The population tested was predominantly men who have sex with men, many of whom were HIV infected. The overall sensitivity and specificity of the oral fluid assay was 95.8 and 86.1%, respectively, based on the 5th percentile of the positive results, and 93.7 and 91.1%, respectively, based on a cutoff derived by mixture model analysis. For individuals with primary syphilis, the optimum sensitivity of the oral fluid assay was 87.5%, whereas in those with disease classified as secondary syphilis and early latent syphilis, the sensitivity of the oral fluid assay was 100 and 94.7%, respectively. The oral fluid assay is a useful alternative to serological testing in certain situations, and further development of this technology to enable detection of treponemal IgM should increase its sensitivity for detecting cases of primary syphilis.

Adult↗
PubMed1982

Cloning and expression of Treponema pallidum protein antigens in Escherichia coli.

Difficulties in culturing the bacterium Treponema pallidum have greatly hindered syphilis research. Recently, several laboratories have accomplished the expression of T. pallidum antigens in Escherichia coli. It is anticipated that treponemal antigens produced by recombinant DNA technology will provide new tools for investigating the pathogenesis and immunobiology of T. pallidum infection.

Antigens, Bacterial↗
PubMed1999

Bayes' theorem-based assessment of VDRL syphilis screening miss rates.

BACKGROUND AND OBJECTIVES: Interlaboratory differences (and conflicting practices) in syphilis screening strategies (serial versus parallel test combinations) prompted us to determine an estimate of the diagnostic miss rate in the detection of (1) infected persons and (2) infected but untreated persons potentially affected by late active syphilis. GOAL: We set out to establish the most efficient syphilis screening strategy for two routine tests (VDRL and Treponema pallidum hemagglutination assay [TPHA]) with regard to our tested public health population (average VDRL+ TPHA+ and VDRL- TPHA+ reactor ages being 59.9 years and 50.5 years, respectively. STUDY DESIGN: Retrospective analysis covered the results of a routine parallel VDRL and TPHA testing on 24,863 persons done in four public health laboratories. Nosologic sensitivity of the VDRL test (18.32%) was determined using the TPHA test as reference. The percentage of VDRL nonreactors among infected persons (TPHA reactors) was considered as the VDRL false negative rate (81.68%). We estimated the proportion of persons infected but untreated with potential late active syphilis using our own Bayes theorem-based procedure. RESULTS: The Bayes theorem-based estimate showed a significantly higher value for persons at risk of active late syphilis than the number of suspected cases obtained using the classical approach (25.1% versus 18.32%, or 83 persons versus 61 of the 330 infected). CONCLUSION: In screening an older population, the VDRL test alone (or as the first of a series with TPHA as a confirmation test) may produce a diagnostic miss rate higher than the syphilis detection rate. Another miss in such a population is detected by the Bayes theorem-based method.

Adult↗
PubMed1995

[Azithromycin and genital infections].

The lower genital tract infections due to Chlamydia trachomatis are frequent, essentially occurring in young patients, with possible complications and severe sequela, particularly in women where the sterility risk is one of the major consequences. If an effective treatment could be systematically proposed, a good compliance (easy administration and good toleration) is one of the key factor to success. In this context, the azithromycin displays numerous advantages. The azithromycin in vitro activity on Chl. trachomatis strains is permanent with MIC comprised between 0.06 and 0.125 micrograms/ml, with an activity equivalent to those of other macrolides, to tetracyclines and quinolones. Different animal models allow to demonstrate the curative activity of the azithromycin administered as a single dose, at dosage regimen equivalent to those used in man, and a prophylactic activity on the salpingitis onset in provoked Chl. trachomatis infections. Several comparative clinical studies with azithromycin administered as a 1 g single dose displayed very satisfactory results with 98% of bacterial eradication, identical to those obtained with reference treatment. On the other hand, restrictions to the product use are a less constant activity against Neisseria gonorrhoeae and a lack of efficacy on Mycoplasma hominis. The efficacy on Treponema pallidum remains to be clinically tested.

Adult↗
PubMed2000

rpoB gene analysis as a novel strategy for identification of spirochetes from the genera Borrelia, Treponema, and Leptospira.

Spirochetes are emerging pathogens for which culture and identification are partly unresolved. In fact, 16S rRNA-based sequencing is by far the most widely used PCR methodology that is able to detect such uncultivable pathogens. However, this assay actually has some limitations linked to potential problems of contamination, which hampers diagnosis. To circumvent this, we have devised a simple PCR strategy involving targeting of the gene encoding the RNA polymerase beta subunit (rpoB), a highly conserved enzyme. The complete sequence of the Leptospira biflexa (serovar patoc) rpoB gene was determined and compared with the published sequences for Borrelia burgdorferi and Treponema pallidum. From the resulting analysis, degenerate nucleotide primers were designed and tested for their ability to amplify a portion of the rpoB gene from various spirochetes. Using two different pairs of these primers, we succeeded in obtaining specific rpoB-amplified fragments for all members of the genera Leptospira, Treponema, and Borrelia tested and no other bacteria. Our findings may have significant implications for the development of a new tool for the identification of spirochetes, especially if clinical samples are contaminated or when the infecting strain is uncultivable.

Borrelia↗
PubMed1999

Human T lymphotropic virus type I (HTLV-I) infection in neurological patients in Salvador, Bahia, Brazil.

HTLV-I infection represents a major health concern in endemic areas throughout the world, such as Salvador, the main city of Bahia State, with socio-demographic characteristics similar to sub-Saharan African cities, located in the Northeast of Brazil. In order to provide an estimate of the frequency distribution, and range of neurological manifestations potentially related to HTLV-I infection in this city, we conducted a cross-sectional clinical-epidemiological study to determine the prevalence of this infection in patients with neurological diseases. Patients exhibiting vascular diseases, tumoral diseases or trauma were excluded. Over a period of 16 months, we studied 322 consecutive patients with chronic neurological diseases, who attended the neurological clinics of two major hospitals in Salvador. Overall, the prevalence of HTLV-I infection among the patients was 20.9% (67/320). However, the prevalence among the 104 patients with chronic myelopathy was 50.0% (52/104). It was observed that the major prevalence of HTLV-I was between the ages of 40 and 60 years with a female predominance. Our data indicate that, in Salvador city, HTLV-I is associated with chronic myelopathies or myeloneuropathies, which seem to be the only neurological diseases associated with HTLV-I.

Adolescent↗
PubMed2002

Infectious myelopathies.

Although infectious myelopathies are rare, timely and accurate diagnosis is essential to improving outcome. There are a number of organisms that may cause infectious myelopathies, including human immunodeficiency virus (HIV), human T-cell lymphotropic virus type I (HTLV-I), herpesviruses, enteroviruses, Treponema pallidum, Mycobacterium tuberculosis, fungi, and parasites. Vacuolar myelopathy, the most common form of spinal cord disease in HIV-infected individuals, is underrecognized clinically. The failure to diagnose this condition is generally a consequence of the attribution of the lower extremity weakness and paresthesias to general debility and concomitant peripheral neuropathy. Tropical spastic paraparesis or HTLV-I-associated myelopathy involves the pyramidal tracts, chiefly at the thoracic level, and results in spastic lower extremity weakness and a spastic bladder. The herpesviruses (varicella-zoster, herpes simplex type 2, cytomegalovirus) and the enteroviruses cause myelitis. Prior to the development of antibiotics, syphilis was the most frequent infectious cause of spinal cord disease. In light of the broad spectrum of pathogens that may affect the spinal cord and the variegate fashion in which these disorders may present, the physician must always consider an infectious etiology in the differential diagnosis for the patient presenting with myelopathy. This review addresses the infectious myelopathies by microorganism.

Central Nervous System Fungal Infections↗
PubMed1985

Isolation of a spirochete from the soft tick, Ornithodoros coriaceus: a possible agent of epizootic bovine abortion.

A Borrelia-like spirochete was detected in all three parasitic stages of Ornithodoros coriaceus, the soft tick implicated in the epizoology of epizootic bovine abortion. After the spirochete had been isolated, its distinctness from other North American tick-borne borreliae as well as from Spirochaeta aurantia, Treponema pallidum, and Leptospira interrogans serovar pomona was established on the basis of its morphology, protein components, and inability to infect mice. The spirochete is passed trans-stadially and via eggs by ticks, and it is also excreted in coxal fluid after ticks have fed and detached. Circumstantial evidence suggests that the spirochete may be causally related to epizootic bovine abortion.

Abortion, Veterinary↗