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PubMed2003

Increasing relative prevalence of HSV-2 infection among men with genital ulcers from a mining community in South Africa.

OBJECTIVES: To determine the aetiology of genital ulcer disease (GUD) and its association with HIV infection in the mining community of Carletonville, South Africa, from two cross sectional surveys of consecutive men presenting with genital lesions during October 1993 to January 1994 and July to November 1998. METHODS: A multiplex polymerase chain reaction (M-PCR) assay combined with amplicon detection was used to identify DNA specific sequences of Treponema pallidum, herpes simplex virus (HSV), and Haemophilus ducreyi. A real time PCR assay was used to differentiate between HSV-1 and HSV-2. RESULTS: M-PCR detected T pallidum, HSV, and H ducreyi in 10.3%, 17.2%, and 69.4% of 232 GUD patients during 1993-4 and in 12.4%, 36.0%, and 50.5% of 186 GUD patients in 1998. The proportion of patients with more than one agent increased significantly from 7.3% (17/232) in 1993-4 to 16.7% (31/186) in 1998 (p <0.01). HSV-2 was detected in a higher proportion of ulcer specimens from HIV infected patients than in specimens from HIV uninfected patients during both time periods (1993-4: 26.2% v 6.7%, p <0.001; 1998: 42.1% v 29.6%, p >0.09). CONCLUSIONS: Based on two cross sectional surveys, 4 years apart, chancroid remained the leading cause of GUD in men who presented at the STD clinic with genital ulcers in the mining community of Carletonville, South Africa. The relative prevalence of primary syphilis has remained low. However, HSV-2 has emerged as a more significant cause of GUD and the proportion of GUD patients infected with more than one agent also increased significantly. HSV-2 DNA was detected in a significantly higher proportion of ulcer specimens from HIV positive patients than from HIV negative patients. No association was found between HIV infection status and the relative prevalence of chancroid or syphilis.

Adult↗
PubMed1997

Sexual behavior risk factors associated with bacterial vaginosis and Chlamydia trachomatis infection.

BACKGROUND AND OBJECTIVES: Few studies have demonstrated that bacterial vaginosis (BV) is associated with sexual behavior risk factors similar to those for other sexually transmitted diseases. The objective of this study was to determine the prevalence of these factors in a multivariate analysis of data from women infected with BV and Chlamydia trachomatis, and noninfected control subjects. GOALS: To study detailed sexual behavior risk factors reported by women with BV versus genital C. trachomatis infection (CT) and by non-BV-infected controls. STUDY DESIGN: A cross-sectional study was conducted with 1,011 women (Swedish Women's Health Study) recruited from family planning and youth clinics in Eskilstuna and Stockholm, Sweden (November, 1989-January, 1991). Participants were evaluated for the presence of BV, CT, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, and human immunodeficiency virus, and interviewed in detail with respect to sexual behaviors. Statistical comparisons were made using chi-square test (Pearson and likelihood ratio), t test, and logistic regression multivariate analysis. RESULTS: Of 956 women eligible for analysis, the prevalence of BV and CT was 13.7% and 8.9%, respectively. The comparison group consisted of the remaining 825 women without BV. After excluding those with concomitant CT infection, there were 118 women with BV who were compared with 72 women with CT infection only. Sexual factors associated with BV versus the comparison group were a short-term relationship before and after sexual debut, high number of lifetime sexual partners, multiple partners during the last month, high orgasm ability, and more frequent history of group sex, sexual abuse, and rape. When the BV group was compared with the CT group, there were no significant differences in sexual activity risk factors, except for a higher frequency of experience of casual sex in the CT group. CONCLUSIONS: Bacterial vaginosis is associated with sexual behavior risk factors similar to those associated with genital CT infection.

Adult↗
PubMed1978

Microassay for immunoglobulin G antibodies to Treponema pallidum with radioiodinated protein A from staphylococcus aureus: immunoglobulin G response in experimental syphilis in rabbits.

Radioiodinated staphylococcal protein A (SpA) was used to detect the immunoglobulin G (IgG) antibody response to Treponema pallidum in experimental syphilis. This solid-phase assay is based on the principle that SpA binds avidly to the Fc portion of mammalian IgG. The optimal number of organisms for detection of antibody was 10(5) per microwell. Of eight fixatives, 10% ethanol gave an optimum immune binding ratio of infected to normal rabbit serus at a 1:100 serum dilution. Kinetic studies demonstrated maximum binding and the highest immune binding ratio (15:1) with a 60-min incubation each for antibody and (125)I-SpA, respectively. The IgG response in rabbits intratesticularly infected with live T. pallidum and bled at -1, 9, 30, 90, 180, and 480 days was detected first at 9 days, reached a peak at 30 days, and remained elevated for 480 days. Absorption studies with an extract of T. phagedenis biotype reiterii demonstrated that 65 to 85% of the total antitreponemal IgG response was specific for T. pallidum throughout the course of infection. The microassay was quantitative and detected less than 2 ng of antibody.

Animals↗
PubMed1984

Immunological cross-reaction between antigen Tp-4 of Treponema pallidum and an antigen common to a wide range of bacteria.

By electro-immunoprecipitation methods it was shown that antigen Tp-4 of Treponema pallidum, antigen TR-c of the Reiter treponeme and 'Common Antigen' of Pseudomonas aeruginosa are immunologically cross-reactive. This finding establishes a taxonomic relationship between T. pallidum and a wide range of bacteria. The cross-reactivity explains some false positive reactions in serodiagnostic treponemal tests for syphilis. The cross-reactivity may also play a role in a possible 'normal' immunity against infection with T. pallidum induced by antigens by the normal human bacterial flora.

Antigens, Bacterial↗
PubMed1989

Ocular manifestations of endemic syphilis (bejel).

Bejel or nonvenereal syphilis is a treponemal infection that is still endemic in many parts of the world including Saudi Arabia. The authors have examined 17 patients with clinical findings consistent with bejel. All patients had positive serologic tests for bejel. There were 11 male and six female patients, with a mean age of 54 years (range, 37-73 years). Results of clinical examination showed uveitis in nine patients, optic atrophy in six, and chorioretinitis scars in six. In four patients who needed intraocular surgery, two aqueous specimens showed positive antibodies for Treponema pallidum.

Adult↗
PubMedDate not supplied

Surface antigens of the syphilis spirochete and their potential as virulence determinants.

A unique physical feature of Treponema pallidum, the venereally transmitted agent of human syphilis, is that its outer membrane contains 100-fold less membrane-spanning protein than the outer membranes of typical gram-negative bacteria, a property that has been related to the chronicity of syphilitic infection. These membrane-spanning T. pallidum rare outer membrane proteins, termed TROMPs, represent potential surface-exposed virulence determinants and targets of host immunity. Only recently has the outer membrane of T. pallidum been isolated and its constituent proteins identified. Five proteins of molecular mass 17-, 28-, 31-, 45-, and 65-kDa were outer membrane associated. The 17- and 45-kDa proteins, which are also present in greater amounts with the T. pallidum inner membrane protoplasmic cylinder complex, had been previously characterized lipoproteins and are, therefore, not membrane-spanning but rather membrane-anchored by their lipid moiety. In contrast, the 28-, 31-, and 65-kDa proteins are exclusively associated with the outer membrane. Both the purified native and an Escherichia coli recombinant outer membrane form of the 31-kDa protein, designated Tromp1, exhibit porin activity, thereby confirming the membrane-spanning outer membrane topology of Tromp1. The 28-kDa protein, designated Tromp2, has sequence characteristics in common with membrane-spanning outer membrane proteins and has also been recombinantly expressed in E. coli, where it targets exclusively to the E. coli outer membrane. The 65-kDa protein, designated Tromp3, is present in the least amount relative to Tromps1 and 2. Tromps 1, 2, and 3 were antigenic when tested with serum from infection and immune syphilitic rabbits and humans. These newly identified TROMPs provide a molecular foundation for the future study of syphilis pathogenesis and immunity.

Animals↗
PubMed2001

Screening of patients with complex regional pain syndrome for antecedent infections.

OBJECTIVE: This study was designed to investigate whether Complex Regional Pain Syndrome type I (CRPS I) could be linked to any previous infection. PATIENTS: Fifty-two patients with CRPS I of one extremity were screened for the presence of antibodies against mostly neurotropic microorganisms. RESULTS: Of these 52 patients, none had antibodies against Treponema pallidum, Borrelia burgdorferi, or HTLV-1. Only four patients were positive for Campylobacter jejuni. For cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and Toxoplasma gondii, seroprevalences were similar to control values. The total seroprevalence of Parvovirus B 19 in our CRPS population was 77%, which was significantly higher than in an independent Dutch population group (59%). Seroprevalence in lower extremity CRPS 1 (94%) was significantly higher than in upper extremity CRPS I patients (68%). In this study all patients were seropositive for varicella zoster virus (VZV) antibodies, but a high prevalence of VZV antibodies is similar to its prevalence in a normal population (>90%). CONCLUSIONS: In this study we found a significantly higher seroprevalence of Parvovirus B19 in CRPS I and this is most striking in lower extremity CRPS I patients. Further serologic research in other geographic areas is needed to provide additional information about a potential role of Parvovirus B 19 or other microorganisms in the etiopathogenesis of CRPS I.

Adolescent↗
PubMed1998

Identification and sequence analysis of Treponema pallidum tprJ, a member of a polymorphic multigene family.

TnphoA mutagenesis was used to identify genes encoding exported proteins in a genomic DNA library of Treponema pallidum, the syphilis agent. The nucleotide sequence of an open reading frame (tprJ) that encodes a 755-amino acid protein with a predicted molecular mass of 81.1 kDa was determined. The deduced amino acid sequence of TprJ has homology to the major surface protein of Treponema denticola, a periodontal pathogen. Southern hybridization and genomic DNA sequence analysis indicate that tprJ is a member of a polymorphic multigene family. RT-PCR data showed that tprJ is expressed in treponemes during syphilitic infection. A putative tprJ gene was sequenced from T. pertenue, the closely related yaws agent. The deduced amino acid sequence of T. pertenue TprJ is 87.3% identical to that of T. pallidum TprJ. This is the first report of significant sequence differences within homologous genes of T. pallidum and T. pertenue.

Amino Acid Sequence↗
PubMed1994

Human immunodeficiency virus infection in long-distance truck drivers in east Africa.

BACKGROUND: A cross-sectional survey was performed to determine the seroprevalence and correlates of human immunodeficiency virus (HIV) infection among long-distance truck drivers in Kenya. METHODS: Truck drivers along the Mombasa-Nairobi highway were enrolled at a roadside research clinic. A standardized interview and serologic evaluation for HIV and syphilis were conducted. RESULTS: We enrolled 970 truck drivers and their assistants of whom 257 (27%) had HIV antibodies. In univariate analysis, HIV infection was correlated with older age, non-Kenyan nationality, Christian religion, longer duration of truck driving, travel outside of Kenya, less frequent visits to wives, and more frequent visits to prostitutes. Uncircumcised status, history of genital ulcer disease or urethritis during the previous 5 years, and a positive Treponema pallidum hemagglutination assay for syphilis were each associated with positive HIV serostatus. Univariate correlates of uncircumcised status included younger age, non-Kenyan nationality, Christian religion, travel outside of Kenya, and less frequent visits to prostitutes. There was a significant association between uncircumcised status and 5-year history of genital ulcer disease or serologic evidence of syphilis, but not with 5-year history of urethritis. In multivariate analysis, HIV infection was independently associated with uncircumcised status (adjusted odds ratio [OR], 4.9; 95% confidence interval [CI], 2.8 to 8.4), history of genital ulcer disease (adjusted OR, 2.4; 95% CI, 1.5 to 4.1), history of urethritis (adjusted OR, 1.8; 95% CI, 1.1 to 2.9), more frequent sex with prostitutes (more than once per month; adjusted OR, 1.7; 95% CI, 1.1 to 2.8), and positive T pallidum hemagglutination assay (adjusted OR, 1.2; 95% CI, 1.0 to 1.4). The attributable risk percentage for the association between HIV and uncircumcised status was 70%, and the population attributable risk was 25%. CONCLUSIONS: Truck drivers in east Africa are at high risk of HIV infection. The strongest correlates of HIV seropositivity were uncircumcised status and history of both ulcerative and nonulcerative sexually transmitted diseases.

Adolescent↗
PubMed1992

The outer membrane, not a coat of host proteins, limits antigenicity of virulent Treponema pallidum.

Virulent Treponema pallidum reacts poorly with the specific antibodies present in human and rabbit syphilitic sera, a phenomenon often attributed to an outer coat of host serum proteins. Here we present additional evidence that the limited antigenicity of virulent organisms actually is due to a paucity of proteins in the outer membrane. Initially, we used electron microscopy to demonstrate that the outer membrane is highly susceptible to damage from physical manipulation (i.e., centrifugation and resuspension) and nonionic detergents. Organisms with disrupted outer membranes were markedly more antigenic than intact treponemes as determined by immunoelectron microscopy (IEM) with rabbit syphilitic and antiendoflagellar antisera. Data obtained with a new radioimmunoassay, designated the T. pallidum surface-specific radioimmunoassay, corroborated these IEM findings by demonstrating that the major T. pallidum immunogens are not surface exposed; the assay also was unable to detect serum proteins, including fibronectin, on the surfaces of intact organisms. Furthermore, IEM of T. pallidum on ultrathin cryosections with monospecific anti-47-kDa-immunogen antiserum confirmed the intracellular location of the 47-kDa immunogen. On the basis of these and previous findings, we proposed a new model for T. pallidum ultrastructure in which the outer membrane contains a small number of transmembrane proteins and the major membrane immunogens are anchored by lipids to the periplasmic leaflet of the cytoplasmic membrane. This unique ultrastructure explains the remarkable ability of virulent organisms to evade the humoral immune response of the T. pallidum-infected host.

Animals↗
PubMed1994

The response of symptomatic neurosyphilis to high-dose intravenous penicillin G in patients with human immunodeficiency virus infection.

BACKGROUND: Infection with the human immunodeficiency virus (HIV) may affect both the natural course of syphilis and the response to treatment. We examined the response to treatment with high-dose penicillin G in HIV-infected patients with symptomatic neurosyphilis. METHODS: Neurosyphilis was defined by reactivity in serum treponemal tests for syphilis, neurologic manifestations consistent with neurosyphilis, and a positive Venereal Disease Research Laboratory (VDRL) test on cerebrospinal fluid. We identified 11 HIV-infected patients with symptomatic neurosyphilis; 5 had been treated previously for early syphilis with penicillin G benzathine. Patients were treated with 18 million to 24 million units of penicillin G per day administered intravenously for 10 days. Cerebrospinal fluid was examined approximately 6 and 24 weeks after treatment, when the polymerase chain reaction and rabbit inoculation were used to detect Treponema pallidum. RESULTS: In four of the seven patients studied 24 weeks after treatment, the serum titers on rapid plasma reagin (RPR) testing decreased by at least two doubling dilutions, and four patients had reductions in the cerebrospinal fluid titers on VDRL testing or reverted to nonreactive results. In two patients there was no normalization or improvement in serum titers on RPR testing or cerebrospinal fluid titers on VDRL testing, cell counts, or protein concentrations. One patient relapsed with meningovascular syphilis six months after therapy. T. pallidum was detected by the polymerase chain reaction in cerebrospinal fluid from 3 of 10 patients before treatment, but in none of the 10 post-treatment specimens. CONCLUSIONS: In patients with early syphilis who are also infected with HIV, therapy with penicillin G benzathine may fail, and neurosyphilis may develop. The regimen of high-dose penicillin recommended for neurosyphilis is not consistently effective in patients infected with HIV.

Adult↗
PubMed2003

Etiology of genital ulcer disease and association with human immunodeficiency virus infection in two tanzanian cities.

BACKGROUND: The etiological agent is usually not established in cases of genital ulcer disease (GUD) in Tanzania, since diagnosis and treatment of this disease are based mainly on clinical rather than microbiologic parameters. GUD increases the risk of infection with HIV. However, the association between specific GUD infections and HIV infection has not been fully investigated. GOAL: The goal was to determine the etiology of GUD and the prevalence of HIV infection in patients with GUD in urban areas of Tanzania. STUDY DESIGN: A total of 102 clinical specimens were collected from 52 and 50 patients with GUD in Dar es Salaam and Mbeya, respectively, and from 93 patients with genital discharge in a cross-sectional study. Two polymerase chain reaction (PCR) assays were used to identify either a single target DNA or all three DNAs of the major causes of GUD: Haemophilus ducreyi, Treponema palladum and herpes simplex virus type 2 (HSV-2). The sera from all patients were tested for antibodies to HIV and T palladum. RESULTS: In Dar es Salaam, DNA from HSV-2, and was detected in 63%, 13%, and 2%, respectively, of the 52 genital ulcer specimens. The corresponding figures in Mbeya were 34%, 10%, and 0% of 50 specimens. Overall, 9% of the 102 patients with GUD were infected with both HSV-2 and, and 39/102 genital ulcer specimens (38%) were negative for the DNA of all three pathogens. The HIV infection rates among GUD patients were 46% and 52% in Dar es Salaam and Mbeya, respectively; among the non-GUD patients, the corresponding rates were 35% and 45%, respectively. The HIV infection rate in Dar es Salaam was significantly higher among women (11/14; 78%) than among men (13/38; 34%) (P = 0.004). Among the HIV-seropositive GUD patients, 71% and 46% (P < 0.003) were coinfected with HSV-2 in Dar es Salaam and Mbeya, respectively. Furthermore, women with HSV-2 in Dar es Salaam were significantly more likely to be HIV-infected than men (60% versus 39%; P<or= 0.006). antibodies were detected in 27 (26%) of the 102 GUD patients and 16 (17%) of the 93 non-GUD patients. CONCLUSION: HSV-2 was the most commonly identified agent in the genital ulcer specimens in two urban STD clinics in Tanzania. The prevalence of HIV was high among the STD patients. HSV-2 was detected at significantly higher rates among HIV-seropositive than HIV-seronegative patients with GUD in both Dar es Salaam and Mbeya.

Adolescent↗
PubMed1994

Biological false-positive syphilis test results for women infected with human immunodeficiency virus.

Regardless of the nontreponemal test used for the screening and diagnosis of syphilis, biological false-positive results (BFPs) are documented in 1%-2% of all cases. An association between BFPs and human immunodeficiency virus (HIV) infection in men has been suggested. We conducted a cohort study to determine whether a similar association between HIV seropositivity and BFPs exists for women. Among 156 HIV-seropositive women, 9 (5.8%) had a BFP for syphilis. Among 633 HIV-seronegative women, only 1 (0.2%) had a BFP. When the 25 HIV-seropositive patients and 55 HIV-seronegative patients with reactive rapid plasma reagin tests and microhemagglutination assays for antibodies to Treponema pallidum were excluded from the calculations, 6.9% and 0.2% of HIV-seropositive and HIV-seronegative women, respectively, had BFPs (P < .001; odds ratio, 39.45; 95% confidence interval, 6.4-879.0). An association was found between injection drug use and BFPs for the population of HIV-infected women but did not entirely account for the differences between this group and the HIV-seronegative group.

Adult↗
PubMed1997

Syphilis serology in human immunodeficiency virus infection: evidence for false-negative fluorescent treponemal testing.

Injection drug users were assessed serologically for human immunodeficiency virus infection and syphilis every 6 months. Treatment histories were reviewed for any high-titer biologic false-positive (BFP) reactors, that is, persons with rapid plasma reagin (RPR) titers > or = 1:4 and negative results for fluorescent treponemal antibody absorption (FTA-ABS) tests. Selected sera were analyzed further by immunoblotting for the presence of antibodies reactive with specific Treponema pallidum antigens. Of 112 BFP reactors, 35 (31%) had at least one RPR test reactive at a dilution >1:8 while the FTA-ABS test remained nonreactive. Five reactors (4.5%) converted from nonreactive to reactive by FTA-ABS test; 4 (3.6%) were reactive by FTA-ABS tests but later became nonreactive. Antibodies to T. pallidum membrane antigens were detected in some samples that were persistently nonreactive by FTA-ABS test. Serologic patterns over time, along with very high-titer BFP reactions and reactivity with T. pallidum-specific antigens, suggest that some BFP reactions may represent FTA-negative syphilis.

Antibodies, Bacterial↗
PubMed1996

[Immunologic studies in the differential diagnosis of infectious endocarditis and septicemia without endocardiac lesion].

Differential diagnosis between infective endocarditis and septicemia without endocarditis remains a crucial clinical difficulty. Value of immunological data during those pathologies has been evaluated in a 2 year prospective study. Sixty-one patients, admitted in an internal medicine and infectious diseases unit for a documented infectious disease, were included. They were separated in three groups: group I (n = 21): demonstrated infective endocarditis; group II (n = 19): septicemia without endocarditis and group III (n = 21): non septicemic well-defined infectious disease. Following parameters were studied: immune circulating complexes, C reactive protein, erythrocyte sedimentation rate, fibrinogen, rheumatoid factor, antinuclear antibodies, Treponema pallidum serodiagnostic and cryoglobulinemia. There were no differences between the three studied groups. In particular, immune circulating complexes were present in respectively 67%, 58% and 62% of the patients of the three groups. So, presence or absence of immunologic abnormalities does not provide help for diagnosis of endocarditis in a febrile patient.

Adult↗