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Validity of prior absorption of serum samples with Reiter's spirochetes in serological diagnosis of Borrelia burgdorferi infections.

Evidence of Borrelia burgdorferi sensu lato infection was sought in 230 patients with positive antibody titres in an indirect immunofluorescence test that became negative after serum samples were preabsorbed with treponemal antigen. Infection could be excluded in 82.2% (189/230) of patients, was questionable in 6.9% (16/230), and was judged to have occurred in 10.9% (25/230), including four (1.7%) cases of early, acute disease that required treatment. The preabsorption procedure clearly reduces the frequency of false-positive reactions; however, there is a definite risk of overlooking active infections with this technique.

Antibodies, Bacterial↗

Syphilis: reemergence of an old adversary.

OBJECTIVE: To describe the clinical findings in 4 patients with ocular syphilis and to provide a review of the recent rise in syphilis cases in the United States, along with a brief description of current diagnosis and treatment guidelines. DESIGN: Retrospective, observational case series. PARTICIPANTS: Four consecutive patients who presented to our facility during a 6-month interval in 2005 with ocular syphilis. METHODS: Review of clinical, laboratory, photographic, and angiographic records of patients with neurosyphilis who underwent intravenous penicillin G treatment. MAIN OUTCOME MEASURES: Resolution of signs and symptoms of ocular syphilis, including changes in visual acuity. RESULTS: Four patients (3 male: mean age, 46 [range, 39-60 years]; 1 female: age 46 years) demonstrated cerebrospinal fluid findings consistent with neurosyphilis, as evidenced by increased leukocyte counts (>5 white blood cells/mm3), and positive Venereal Disease Research Laboratory or serum fluorescent treponemal antibody absorbed tests. All 4 patients presented with a variety of clinical findings that led to a delay in diagnosis and treatment. Two patients presented with discrete placoid lesions consistent with acute syphilitic posterior placoid chorioretinitis, a manifestation typically observed among the immunocompromised. CONCLUSIONS: Despite a decade of steady decline, syphilis has reemerged in the United States with outbreaks throughout the country in the past few years. Ocular findings, including posterior placoid chorioretinitis, are important diagnostic features in the early treatment of tertiary syphilis and neurosyphilis. Ophthalmologists have the opportunity to play a key role in the early diagnosis and management of this potentially fatal disease.

Adult↗

Surveillance systems for sexually transmitted diseases in Switzerland.

BACKGROUND: In Switzerland (population 7.4 million), 3 different systems contribute to surveillance for sexually transmitted infections. GOAL: The goal of this study was to compare time trends from surveillance systems for chlamydia, gonorrhea, and syphilis. STUDY DESIGN: We studied surveillance data (1997-2003) from laboratory reports in women and men, men attending dermatology clinics, and women attending gynecologists. RESULTS: Laboratory reports of episodes of Chlamydia trachomatis and Neisseria gonorrhoeae increased by 31% (from 2573 to 3449 cases) and 104% (from 259 to 528 cases), respectively. Over the same period, chlamydia reports from men attending dermatology clinics and women attending gynecologists did not change and dermatology clinic-based reports of gonorrhea in men increased only slightly. Syphilis reports from dermatology clinics increased by 127% (from 22 to 50 cases). CONCLUSIONS: Increases in laboratory reports of chlamydia and gonorrhea were not consistently detected in sentinel populations. Numbers of cases reported to all 3 systems were low. The performance of surveillance systems for sexually transmitted infections should be evaluated regularly.

Adolescent↗

Atypical early syphilis in an hiv-infected homosexual male.

A homosexual male, seropositive to HIV and with previously documented syphilitic infections, developed a slowly growing nodule on his left wrist (possibly a chancre) followed, after 2 months, by a few scattered, large papular lesions. Serological evidence of active syphilis was obtained and treponema were identified in the initial lesion by means of immunofluorescent staining. Treatment with both aqueous crystalline penicillin G and benzathine penicillin G healed the lesions. This represents a further case of an atypical presentation of early syphilis in an immunocompromised host.

Acquired Immunodeficiency Syndrome↗

Immunological evaluation and cellular location analysis of the TprI antigen of Treponema pallidum subsp. pallidum.

The TprI antigen of Treponema pallidum subsp. pallidum is a putative virulence factor predicted to be located in the outer membrane of the syphilis spirochete. In this study, we analyzed the immune response against TprI and its subunits in sera collected both from rabbits experimentally infected with the Nichols strain and from patients with syphilis, showing a different pattern of reactivity toward the antigen in these two groups of samples. The protective ability of recombinant TprI and its hypothetical outer membrane location were also investigated. Although no rabbit was protected after challenge, immunoelectron microscopy results, to be further investigated, were compatible with the outer membrane location of the antigen.

Animals↗

Cross-infection from periodontitis sites to failing implant sites in the same mouth.

Twenty-five tooth and implant sites in nine patients were investigated for the presence of putative periodontopathic organisms, using specific DNA probes for Actinobacillus actinomycetemcomitans, Porphromonas gingivalis, Prevotella intermedia, Eikenella corrodens, Fusobacterium nucleatum, Treponema denticola, and Campylobacter recta. Five of nine patients showed a likelihood of transmission from tooth to implant sites. These patients also showed a high number of putative periodontopathic organisms present in the tooth sites tested. A significant risk was found of transmitting putative periodontopathic organisms from periodontitis sites to implant sites in the same mouth. An appropriate clinical protocol needs to be developed to address this issue.

Aggregatibacter actinomycetemcomitans↗

Human T cell lymphotropic virus type I infection among female sex workers in Peru.

Four hundred female sex workers attending a sexually transmitted disease clinic in Lima, Peru, were interviewed for demographic information and medical, contraceptive, and sexual practice histories. Cervical cultures were done for Neisseria gonorrhoeae and Chlamydia trachomatis, and serum was tested for antibodies to human immunodeficiency virus, human T cell lymphotropic virus type I (HTLV-I), Treponema pallidum, C. trachomatis, herpes simplex virus type 2 (HSV-2), and Haemophilus ducreyi. The prevalence of HTLV-I increased with duration of prostitution from 3.6% (< 3 years) to 9.3% (3-6 years) to 15.9% (> 6 years; P < .01). After adjustment for duration of prostitution, reduced risk of HTLV-I was significantly correlated with condom use for more than half of all sexual exposures for > 3 years (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.13-0.89). Further adjusting for condom use, HTLV-I seropositivity was associated with C. trachomatis (OR, 3.7; 95% CI, 1.4-13.2) and with antibody to HSV-2 (OR, 3.7; 95% CI, 0.5-29.6). Thus, duration of prostitution, lack of consistent condom use, and past infection with C. trachomatis were significantly associated with HTLV-I seropositivity.

Adult↗

Nosocomial transmission of syphilis during haemodialysis in a developing country.

Patients with end-stage renal disease (n = 187) secondary to diverse aetiologies who underwent haemodialysis (HD) between November 1996 and November 2000 were routinely screened for syphilis using the rapid plasma reagin (RPR) test and confirmed by means of a microhemagglutination assay for Treponema pallidum. All the confirmed syphilis patients were asymptomatic and were diagnosed serologically. A true seroprevalence of 6.9% (13/187) and a biological false seropositivity of 4.2% (8/187) for syphilis were recorded. Most (11/13) of the true seropositive patients were aged between 51 and 80 y. Whilst 10/13 patients were true syphilis seropositive at the time of first HD, 3/13 patients became true seropositive an average of 12 months (range 10-14 months) after HD. Penicillin treatment was given to all 13 patients simultaneously only after the appearance of 3 new true syphilis seropositive cases. Complete seroreversion was observed in 4/10 patients in the pre-HD true syphilis seropositive group of presumptive transmitters who became RPR-negative, whereas the 3 new true seropositive cases showed a serial 4-fold decline in RPR titres 12 months after penicillin therapy, suggestive of an active disease with adequate therapeutic response. These results clearly indicate that latent syphilis is prevalent in long-term elderly HD patients. The true seroconversion of 3 new patients who had undergone HD for an average of 12 months is indicative of nosocomial transmission and the silently active nature of the disease, which necessitates regular monitoring of syphilis serology among HD patients.

Adolescent↗

Antimicrobial prophylaxis in pregnancy: a randomized, placebo-controlled trial with cefetamet-pivoxil in pregnant women with a poor obstetric history.

OBJECTIVE: This study was undertaken to measure the impact of a single oral dose of cefetamet-pivoxil on pregnancy outcome in a population with substantial rates of low birth weight and high prevalence rates of maternal infections. STUDY DESIGN: A total of 320 pregnant women with a poor obstetric history, defined as a history of low birth weight or stillbirth, were randomized to receive a single oral dose of 2 gm of cefetamet-pivoxil or a placebo at a gestational age between 28 and 32 weeks. Patients were assessed at delivery and 1 week post partum for pregnancy outcome, postpartum endometritis, human immunodeficiency virus-1 and gonococcal infections. RESULTS: A total of 253 (79%) women gave birth at the maternity hospital, of whom 210 (83%) attended the follow-up clinic. Overall, 18.1% of these pregnant women were human immunodeficiency virus-1 seropositive, whereas 9.5% had antibodies against Treponema pallidum. There was a significant difference between cefetamet-pivoxil- and placebo-treated women in infant birth weight (2927 gm vs 2772 gm, p = 0.03) and low birth weight (< 2500 gm) rates (18.7% vs 32.8%, p = 0.01, odds ratio 2.1, 95% confidence interval 1.2 to 3.8). The stillbirth rate was 2.2% in the cefetamet-pivoxil group and 4.2% in the placebo group (not significant). Postpartum endometritis was found in 17.3% in the intervention arm versus 31.6% in the placebo group (p = 0.03, odds ratio 2.2, 95% confidence interval 1.1 to 7.6). Neisseria gonorrhoeae was isolated from the cervix in 5 of 103 (4.9%) women in the intervention and in 14 of 101 (13.9%) in the placebo group (p = 0.04, odds ratio 3.2, 95% confidence interval 1.1 to 10.5). CONCLUSION: A single oral dose of cefetamet-pivoxil administered to pregnant women with a poor obstetric history seemed to improve pregnancy outcome in this population with high rates of maternal infections. Larger studies should be carried out to examine the public health impact, the feasibility, and the overall cost/benefit ratio of this intervention.

Acquired Immunodeficiency Syndrome↗

Phagocytosis of Treponema pallidum and reactive oxygen species production by isolated rat Kupffer cells.

The in vitro phagocytosis of viable Treponema pallidum subsp. pallidum by isolated rat Kupffer cells, studied by immunofluorescence staining of Kupffer cells-associated bacteria, showed that ingestion of live, unopsonized treponemes was slow: in fact, Kupffer cells started to be positive 1 h after infection, when only 4% of the cells presented small round fluorescent inclusion-like bodies. Thereafter, the number of positive cells progressively increased with time: 7%, 17%, 36%, and 69% of Kupffer cells were positive, respectively, 2, 4, 6 and 8 h after infection. Opsonization of T. pallidum with human immune serum did not substantially modify the percentage (8%) of Kupffer cells ingesting T. pallidum 1 h after infection, whereas opsonization significantly ( P<0.01) increased phagocytosis after 2, 4 and 6 h of incubation, when 44%, 58%, and 68% of Kupffer cells were positive, respectively. At 8 h after infection of Kupffer cells by opsonized T. pallidum, 75% of the cells were positive by immunofluorescence. Heat-inactivation of T. pallidum slightly enhanced phagocytosis. In contrast, opsonization of heat-inactivated spirochetes with specific antibodies significantly ( P<0.01) increased the phagocytosis of bacteria by Kupffer cells, beginning as early as 30 min after infection, when 65% of the cells were positive by immunofluorescence. The reactive oxygen species (ROS) production by Kupffer cells following incubation with spirochetes was also determined by chemiluminescence. Treponemes induced an oxidative burst in Kupffer cells in a dose-dependent manner and the generation of ROS was already detectable 20 min after the exposure of the Kupffer cells to treponemes and peaked at 35 min of incubation. Live, as well as live and opsonized, and heat-inactivated treponemes, induced an O(2)(-) production lower than that induced by heat-inactivated and opsonized spirochetes.

Animals↗

Syphilis and human immunodeficiency virus seroconversion during a 6-month follow-up of female prostitutes in Mogadishu, Somalia.

A total of 155 prostitutes inhabiting 4 different districts in Mogadishu, Somalia, were enrolled in a 6 month prospective study of syphilis and HIV infection. Blood samples were taken on entry, at 3 months and at 6 months. Differences were seen between the prostitutes in the 4 districts regarding possible risk factors for the acquisition of STDs. Initially 107 (69%) were found to have syphilis serum markers and 47% had active syphilis as judged by positivity in both Treponema Pallidum Haemagglutination (TPHA) test and non-treponemal (VDRL and RPR) tests. TPHA positivity was correlated to the number of sexual partners. Sixty-nine prostitutes were followed for 6 months. Two of the 16 initially TPHA negative women seroconverted for syphilis during the follow-up. HIV antibodies were detected in one (0.6%) of the 155 prostitutes at the start of the study and one out of 68 seroconverted during the 6 months follow-up. To control the spread of HIV infection health education targeting the risk groups like prostitutes must be given a high priority.

Adolescent↗

[Expanded serologic infection testing of autologous blood donors: a report of experiences].

PURPOSE: The transmission of hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV-1/2) may cause serious disease in the recipient in cases of inadvertant homologous transfusion of autologous blood. Therefore data on the incidence of these infections in autologous blood donors are necessary. METHODS: We tested 7,438 autologous donations from 3,030 patients for anti-HIV, anti-HCV, and HBsAG. In addition, we tested all patients for antibodies to Treponema pallidum and hepatitis B virus core antigen (anti-HBc) and for elevated serum ALT levels. Confirmation tests were performed only for positive anti-HIV-EIAs. RESULTS: The frequencies of anti-HIV, anti-HCV, and HBsAG were 0.05, 2.8 and 0.6% of all units. The rate of anti-HCV decreased from 4.0 to 3.4% after introduction of a 2nd generation EIA but was only 0.6% using a 3rd generation EIA. Anti-HBc was positive in 9.4%, the TPHA test in 0.5%. ALT was above 45 U/I in 1.2%, but outside the sex related normal range in 8.4% of all units. 23.7% of all donations positive for anti-HIV, anti-HCV, or HBsAG showed at least one pathologic surrogate test; 7.5% of all surrogate marker positive units contained anti-HIV, anti-HCV, or HBsAG. DISCUSSION: The overall frequency of anti-HIV, anti-HCV, and HBsAG was only 3.45% of all autologous donations and was reduced further after introduction of 2nd and 3rd generation anti-HCV-EIAs. However, the rate of surrogate marker positive units was 10.9%. The overlap between both groups was remarkable. We conclude from our data that procedures to minimize the risk of inadvertant homologous transfusion of autologous blood are necessary despite the implementation of screening tests in autologous donation programs.

Adolescent↗

The modern diagnosis of syphilis.

After briefly outlining the natural history of syphilitic infection, the authors review in detail the diagnosis of syphilis in the various stages of the disease and discuss the relative value at each stage of the commonly used serological tests and the Treponema pallidum immobilization (TPI) test. In their conclusions, they remark that the TPI test should be used with discretion and not as a matter of routine with all sera. Owing to its complexities and to the lengthy procedure involved, it is better suited for use with "problem" sera, for instance, sera from expectant mothers suspected of being acute non-treponemal reactors, or sera from persons with latent syphilis.

Humans↗

Treatment of neurosyphilis.

In 2001, the incidence of primary and secondary syphilis increased in the United States for the first time in a decade. Increasing rates of early syphilis among men who have sex with men have been reported in many American cities, with similar outbreaks noted in Canada and Europe. In San Francisco, the increase has been particularly sharp and accompanied by an increase in the incidence of neurosyphilis. Early neurosyphilis develops within weeks to years of primary infection and primarily involves the meninges. Syndromes include syphilitic meningitis (often accompanied by cranial neuropathies), meningovascular syphilis (with associated ischemic stroke), or asymptomatic neurosyphilis. Late neurosyphilis occurs years to decades after exposure as cerebral or spinal gummatous disease or the classic parenchymal forms affecting the brain (general paresis or syphilitic encephalitis) or spinal cord and nerve roots (tabes dorsalis). Treponema pallidum, the causative agent, cannot be cultured in vitro, and microscopic techniques are laborious. Thus, diagnosis depends on serologic tests and cerebrospinal fluid (CSF) examination. The suboptimal sensitivity and specificity of these tests complicate diagnosis, particularly among patients coinfected with HIV. CSF examination should be performed to evaluate for neurosyphilis in all patients with positive serum syphilis serology and neurologic, ophthalmic, or tertiary disease, or in those who have failed therapy, and in HIV-infected patients with late latent syphilis or syphilis of unknown duration. Intravenous penicillin G is the recommended treatment for all forms of neurosyphilis and for syphilitic eye disease. An outpatient alternative, if adherence can be assured, is intramuscular benzathine penicillin with oral probenecid. Newer drugs that penetrate CSF, such as ceftriaxone or azithromycin, have not yet been adequately tested for neurosyphilis. Syphilis facilitates transmission of HIV (and vice versa), and thus all patients diagnosed with syphilis should be offered HIV testing.

Journal Article↗

Genetic and physicochemical characterization of the recombinant DNA-derived 47-kilodalton surface immunogen of Treponema pallidum subsp. pallidum.

Previous work has established the importance of the 47-kilodalton (kDa) surface immunogen of Treponema pallidum subsp. pallidum (T. pallidum) in the immunopathogenesis of syphilis; the 47-kDa immunogen gene was cloned and expressed in Escherichia coli (M. V. Norgard, N. R. Chamberlain, M. A. Swancutt, and M. S. Goldberg, Infect. Immun. 54:500-506, 1986). To facilitate additional structural-functional analysis of this protein for immunopathogenesis studies, the recombinant DNA-derived molecule was examined with respect to its genetic expression and physicochemical properties. Subcloning of partial PstI digests of the original 47-kDa antigen-encoding DNA segment localized the 47-kDa antigen gene to a 1.3-kilobase (kb) T. pallidum DNA fragment. A 20- to 100-fold enhanced expression of the 47-kDa antigen was obtained when a 2.85-kb DNA insert containing the entire 1.3-kb structural gene was subcloned into a T7 RNA polymerase-dependent expression vector system. Under these conditions, several derivatives of the recombinant 47-kDa protein possessing different molecular masses were observed that were identical to those previously detected on Western blots of native T. pallidum antigens with monoclonal antibodies. Sarkosyl extraction of E. coli recombinant cell envelopes localized the 47-kDa protein to both the inner and outer membranes of E. coli. The absolute requirement of detergents (N-lauroylsarcosine, 3-[(3-chloramidopropyl)dimethylammonio]-1-propane sulfonate, N-octyl-beta-D-glucopyranoside, or Nonidet P-40) for solubilization of the antigen from E. coli cell envelopes and the observation that the recombinant protein partitioned into the detergent phase on Triton X-114 solubilization were consistent with the fact that it is a hydrophobic, integral membrane protein. Western blots of the 47-kDa antigen purified by immunoaffinity chromatography supported results of previous reports that the 47-kDa protein is specific to pathogenic treponemes.

Antigens, Surface↗

Reactivity of antibodies from syphilis patients to a protein array representing the Treponema pallidum proteome.

To identify antigens important in the human immune response to syphilis, the serum antibody reactivity of syphilitic patients was examined with 908 of the 1,039 proteins in the proteome of Treponema pallidum subsp. pallidum using a protein array enzyme-linked immunosorbent assay. Thirty-four proteins exhibited significant reactivity when assayed with human sera from patients in the early latent stage of syphilis. A subset of antigens identified were further scrutinized for antibody reactivity at primary, secondary, and latent disease stages, and the results demonstrate that the humoral immune response to individual T. pallidum proteins develops at different rates during the time course of infection.

Antibodies, Bacterial↗

Associations between Porphyromonas gingivalis and oral treponemes in subgingival plaque.

Colonization and/or proliferation of Treponema denticola may depend on the presence of Porphyromonas gingivalis. The aims of this study were to confirm this synergistic relationship, to determine whether other oral bacteria were similarly associated with P. gingivalis and to relate coinfection to the periodontal status of plaque donors. Subgingival plaque was collected from every tooth except third molars in 106 subjects who were grouped by their worst periodontal condition. In addition to P. gingivalis, monoclonal antibodies were used to identify Campylobacter rectus, Eikenella corrodens, T. denticola, Treponema socranskii and pathogen-related oral spirochetes. Associations of these bacteria with coinfection by P. gingivalis were assessed by estimated odds ratios. The results indicate that coinfection with P. gingivalis is linked to all tested bacteria, but each pair was associated with distinct periodontal conditions. The distribution of coinfected sites suggests biased colonization of facial surfaces over lingual surfaces.

Adult↗