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Laboratory investigation of syphilis.

Without treatment, syphilis passes through primary, secondary, latent, and tertiary stages. The disease can be diagnosed directly by microscopic identification of the infective organism or serologically. Nontreponemal serologic tests are most suitable for screening and following response to therapy, while treponemal tests are used to confirm a positive nontreponemal test result. Biologic false positives are not uncommon. Because of the danger of infection to the fetus, serologic testing for syphilis is mandatory in all pregnant women. Nontreponemal tests can also be performed on CSF to document neurosyphilis.

False Positive Reactions↗

[Treponemal hemagglutination test (TPHA). Validity of the micromethod using dilutions of sera 1/20-1/40].

The Authors studied the possibility to use, for the carrying out of the TPHA micromethod, higher serum dilutions, as preliminary investigations had pointed out an insufficient sensitivity of the reaction performed at the 1:80 - 1:160 dilutions, particularly in the primary-secondary phase of the luetic infection. The Authors controlled, preliminarily, that at the dilutions studied, no unacceptable increase of spontaneous hemagglutinations and false positive reactions took place in the test sera. The investigation stressed the acceptability of the methodological modification set forth.

Hemagglutination Tests↗

Susceptibility of Treponema pallidum to the toxic products of oxygen reduction and the non-treponemal nature of its catalase.

We examined the sensitivity of Treponema pallidum (Nichols strain) to toxic products of oxygen reduction. T pallidum was sensitive to hydrogen peroxide at concentrations similar to those to which obligate anaerobes are sensitive. Accelerated death of T pallidum occurred at hydrogen peroxide concentrations below 50 mumol/l. Agents protective against hydrogen peroxide and the hydroxyl free radical (catalase, peroxidase, and mannitol) significantly enhanced treponemal survival in vitro under all three conditions of aerobiosis tested--that is, air, 3% oxygen, and 3% oxygen in conjunction with a reduced medium. Superoxide dismutase (which provides protection against superoxide radicals) did not enhance treponemal survival in normal media. When superoxide radicals were generated in the medium by means of a xanthine and xanthine oxidase system, however, the enzyme did protect T pallidum. A possible toxic involvement of singlet oxygen was also indicated by enhanced treponemal survival in air in the presence of histidine. Extracts of T pallidum from infected rabbit testes showed catalase activity which, on polyacrylamide gel electrophoresis, had the same relative mobility as purified rabbit catalase. The treponemal catalase activity was neutralised by anti rabbit catalase antiserum (raised in guinea pigs). This confirmed that the catalase was of rabbit origin and not an endogenous enzyme of T pallidum. We discuss the relation of these results to the obligate parasitism of T pallidum.

Animals↗

Diagnosing genital ulcer disease in a clinic for sexually transmitted diseases in Amsterdam, The Netherlands.

The most common etiologic agents of genital ulcer disease (GUD) are herpes simplex virus type 1 (HSV-1), HSV-2, Treponema pallidum, and Haemophilus ducreyi. In an outpatient clinic for sexually transmitted diseases in Amsterdam, The Netherlands, specimens from 372 patients with GUD were collected from February to November 1996. Sera were collected at the time of the symptoms and, for most patients, also during follow-up visits. Swabs in viral transport medium were used for HSV culture and for detection of DNA. The most prevalent pathogen found was HSV-2, which was detected by culture in 35% of the patients and by PCR in 48% of the patients. Also, HSV-1 infection was more often detected by PCR (7.8%) than by culture (5.6%). Evidence for an active infection with T. pallidum was found in 1.9% of the patients, using serological tests. A multiplex PCR for simultaneous T. pallidum and H. ducreyi DNA detection was positive for T. pallidum in 3.3% of the samples and for H. ducreyi in only 0.9% (3 out of 368) of the samples. The sensitivity of the PCR was superior to that of culture for HSV detection and to that of serology for T. pallidum detection. Specific H. ducreyi immunoglobulin G antibodies were detected in sera of 5.2% of the patients, with no concordance between serology and PCR. In 37% of the cases, none of the tested microorganisms was detected. Performance of PCR in addition to conventional techniques significantly improved the diagnosis of GUD.

Chancroid↗

Etiology of nonvesicular genital ulcers in Winnipeg.

Twenty-eight patients with recent onset of nonvesicular ulcerative genital lesions were studied prospectively to define the microbial etiology. Causative agents identified included herpes simplex virus (HSV), Chlamydia trachomatis, Haemophilus ducreyi, and Treponema pallidum. Three women and 25 men (seven of whom were homosexual) were studied. Ten patients did not have an etiology identified. Nine patients had syphilis, six had genital herpes, one had chancroid, one had granuloma inguinale, and one had a human bite injury. Six of seven homosexual men had syphilis, as compared with one of eight heterosexual men (P less than .002). Among heterosexual men, five had atypical HSV infections, three with extensive balanoposthitis and two with chancroidal ulcers. Of the clinical characteristics examined, induration of the ulcer base and tenderness on palpation were predictive of etiology, whereas numbers of ulcers and regional lymphadenopathy were not. H. ducreyi was not a common cause of genital ulcers in Winnipeg, and it was not found as a commensal or superinfecting organism in ulcers caused by other agents.

Adolescent↗

A case-control study of stillbirths at a teaching hospital in Zambia, 1979-80: serological investigations for selected infectious agents.

Sera were obtained from 266 mothers of singleton stillborn babies (cases) and 266 mothers of live-born babies (controls), matched for parity, who delivered at the University Teaching Hospital, Lusaka, Zambia, between October 1979 and April 1980. Tests were performed on 262 samples from cases and 261 from controls. The microhaemagglutination assay for Treponema pallidum (MHA-TP) was reactive in 54% of cases and 29% of controls; the rapid plasma reagin (RPR) 18-mm circle card test was reactive at a dilution of 1:16 or greater in 29% of cases and in 3.5% of controls. Both these differences are highly significant.Sera from cases and controls were further examined for evidence of cytomegalovirus, human (alpha) herpesvirus, hepatitis B virus, toxoplasma, and plasmodium infections. The only difference between sera from cases and controls was that cytomegalovirus antibody titres >/= 1:1024 occurred more often among cases. There was no relationship between antibody titre and birth weight.The results of this study emphasize the importance of screening pregnant women for syphilis. Treatment of those found to be infected should help prevent stillbirths due to syphilis.

Antibodies↗

Transmission of syphilis by solid organ transplantation.

Two organ recipients developed serologic evidence of syphilis infection after renal transplantation from a common deceased donor with a history of treated syphilis. Testing of donor serum for syphilis, which occurred after transplantation, gave results interpreted as consistent with past infection. However, subsequent serologic results in the recipients suggested transmission of infection at transplantation due to active infection of the donor. This may be explained by recent donor re-infection in view of the current syphilis epidemic in the United Kingdom. An initial error in the treatment of recipients further served to highlight unfamiliarity in managing this resurgent infection in the context of organ transplantation.

Adult↗

Diagnostic relevance of polymerase chain reaction technology for T. pallidum in subjects with syphilis in different phases of infection.

Although serology is a valid tool for the clinician to manage syphilis infection, there are still some cases in which evidence of the presence of T. pallidum or its specific components, such as specific DNA segments, may be useful to establish or confirm the diagnosis. In the absence of T. pallidum grown in culture, a nested PCR to amplify a specific segment of the microorganism genome was performed in ulcerative secretions or sera, after DNA extraction, using a commercially available kit. A kit validation was based on the observation of no positivities in patients without ongoing or anamnestic infection (40 patients). On the contrary, patients infected with T. pallidum presented positivities both in ulcerative secretions and in sera with frequencies that depended on the disease phase and type of sample. In fact, even after treatment, ulcerative secretions that were negative in dark-field examination were found to be positive in PCR. In addition, the sera of patients with positive specific IGM (serologically diagnosed syphilis, asymptomatic state) were also positive in PCR. This test could, therefore, be useful to analyze difficult situations, especially when a seropositivity for a previous infection may complicate the serology of a reinfection or when therapies interfere with dark-field microscopic observation.

Antibodies, Bacterial↗

Tropical ulcers.

We review 230 cases of tropical ulcers, includied reports of 7 cases with squamous cell carcinoma. We think the etiology may be a combination of the hot, humid environment, trauma, local infection, and malnutrition. Agressive treatment of these ulcers is advocated, to heal the wounds and to prevent malignant transformation.

Adult↗

Effect of immunosuppressive agents on the course of experimental syphilis in rabbits.

Rabbits infected intradermally with T. pallidum at four sites on the clipped back were treated with cyclophosphamide, 1 mg/kg body weight, twice before and every two days after inoculation for five months, or 5-fluorouracil 2.5 mg/kg body weight, according to the same regimen. Humoral response, as measured repeatedly by VDRL, FTA, and hemagglutination tests, was not affected by the application of the immunosuppressors. In contrast, the cell-mediated response, as determined by the Macrophage Migration Inhibition test was completely abolished in the treated rabbits. In the group of rabbits which were given immunosuppressors, syphilitic lesions appeared not only at the challenge sites, as usual, but also multiple multiform lesions developed over the entire dorsum after healing of the primary lesions. Taking into account the fact that abolishment of the cell-mediated response led to an aggravated course of the syphilitic infection, the results of these experiments were interpreted as indicating the protective role of the cell mediated response in syphilis.

Animals↗

The absence of HIV seropositivity contrasts with a high prevalence of markers of sexually transmitted infections among registered female sex workers in Toliary, Madagascar.

In a cross-sectional study in 1998 we assessed human immunodeficiency virus (HIV) and syphilis infections and their risk factors among the 316 registered female sex workers (FSWs) of Toliary, south-west Madagascar. No case of HIV infection was detected, but 18.4% of registered FSWs had syphilis. Only half of these women regularly used condoms. In a multiple logistic regression analysis, risk factors for syphilis infection were multiple clients per week and, paradoxically, regular use of condoms. The variables associated with irregular use of condoms were younger ages of registered FSWs, multiple clients per week and Malagasy clients. The high prevalence of syphilis infection associated with irregular use of condoms might facilitate a very fast spread of HIV infection among these FSWs. Promotion of condom use and surveillance of sexually transmitted infections and HIV infection incidence are needed in the south of Madagascar.

Adolescent↗

An evaluation of the Behring Diagnostics Enzygnost Syphilis enzyme immunoassay.

The Enzygnost Syphilis (Behring Diagnostics, Marburg, Germany) was evaluated (i) using sera already characterised using the rapid plasma reagin test and the Treponema pallidum hemagglutination test (TPHA); (ii) prospectively; (iii) using sera which are recognised as causing "problems" with enzyme immunoassays. The Enzygnost Syphilis was found to have a reproducibility of 98.6% and a sensitivity of 99.5% using sera known to be TPHA-reactive. When tested prospectively, the false reactive rate was 3.2%. These results show that the assay performs sufficiently satisfactorily for its introduction as a screening assay for evidence of syphilis infection in our population.

False Positive Reactions↗

Lymphocyte transformation and the effect of circulating immune complexes in humans with syphilis.

Peripheral blood lymphocytes and serum obtained from patients with secondary syphilis were studied in vitro by the technique of lymphocyte transformation. The sera from these patients also were examined for circulating immune complexes by the method of precipitation with polyethyene glycol. The lymphocytes responded poorly to in vitro stimulation with mitogens and treponemal antigens. In addition, the lymphocyte responses were poorer in autologous syphilitic serum than in normal human serum. The serum from some patients with syphilis contained circulating immune complexes that were present during infection, and decreased in amount after treatment with penicillin. In general, lymphocyte responses to mitogen and antigen were greater after therapy.

Antigen-Antibody Complex↗

Bacteriology of experimental gingivitis in children.

Children are more resistant to gingivitis than are adults. To determine possible differences in their periodontal floras, an experimental gingivitis study, identical in design to one reported earlier with young adults, was conducted with four 4- to 6-year-old children. The incidence of sites that developed gingival index scores of 2 in children was less than one-third of the incidence observed in adults. The composition of the flora of each child was statistically significantly different from that of any other child or adult. The floras of the children as a group were statistically significantly different from those of the adults. Children had 3-fold greater proportions of Leptotrichia species, 2.5-fold greater proportions of Capnocytophaga species, 2.3-fold greater proportions of Selenomonas species, 2-fold greater proportions of bacterial species that require formate and fumarate, and 1.5-fold greater proportions of Bacteroides species. Adults had greater proportions of Fusobacterium, Eubacterium, and Lactobacillus species. Fusobacterium nucleatum, Actinomyces WVa 963, Selenomonas D04, and Treponema socranskii were predominant species that correlated with increasing gingival index scores in both children and adults.

Age Factors↗

Seroprevalence of syphilis among women attending urban antenatal clinics in Burkina Faso, 1995-8. The DITRAME Study Group. DIminunation de la TRAnsmission Mère-Enfant.

OBJECTIVES: To describe annual trends in syphilis seroprevalence and to identify risk factors of syphilis among pregnant women receiving antenatal care in Bobo-Dioulasso, Burkina Faso. METHODS: Women were recruited between January 1995 and July 1998 in three antenatal clinics where counselling and HIV testing services had been established in the context of a trial evaluating a short course of zidovudine to reduce mother to child transmission of HIV (ANRS 049 trial). Sociodemographic variables were collected during HIV pretest counselling sessions. Syphilis diagnosis was considered when serum was positive with both rapid plasma reagin and Treponema pallidum haemagglutination assay (TPHA) tests. RESULTS: Overall, 10,980 pregnant women were screened. Syphilis seroprevalence was 0.24% (95% confidence interval (CI): 0.15-0.35) without changes over time. HIV prevalence was 8.8% (CI: 8.3-9.3). In a multivariable analysis, having casual sex partners (odds ratio (OR) = 4.48; CI: 1.62-12.38), being HIV seropositive (OR = 2.62; CI: 1.02-6.74), and being illiterate (OR = 3.78; CI: 1.24-11.48) were independent risk factors for syphilis infection. CONCLUSIONS: This study suggests low syphilis seroprevalence in this city of Burkina Faso. Sexually transmitted disease programmes should be reinforced to offer free access to syphilis screening and treatment in order to eliminate this disease, in coordination with HIV prevention and care.

Adolescent↗

Antibacterial monoclonal antibodies and the dawn of a new era in the control of infection.

Literature reports concerned with monoclonal antibodies against bacteria, or their toxins, which are pathogens for man and animals were surveyed. These antibodies have important potential uses in human and veterinary pathology and medicine. They are likely to become key elements in a fast progression toward a more complete understanding and control of infectious diseases and of toxin poisoning. A new area of bacteriology relevant to sanitary engineering is also being advanced with the help of antibacterial monoclonal antibodies. This area involves bacteria that produce the biofuel methane, along with other molecules of nutritional value, through a process which brings about the recycling of organic wastes and thereby limits or controls microbial contamination of soil and water.

Animals↗

Prevalence of HIV and syphilis in pregnant women in Leon, Nicaragua.

The objective of this study was to determine the prevalence of HIV and syphilis and to identify risk factors among pregnant women visiting antenatal clinics in León, Nicaragua. During February to April 2004, blood samples from pregnant women were collected after written consent had been obtained. The samples were tested for antibodies against HIV and Treponema pallidum. A questionnaire was also completed. In total, 1,059 women were included. Antibodies against HIV were not detected in any of the women, whereas antibodies against T. pallidum were detected in 16 (1.5%). Risk factors for syphilis included illiteracy, lower education, and two or more pregnancies. HIV does not seem to be highly prevalent among pregnant women in León (prevalence, 0%; 95% CI, 0.0-0.3). The higher proportion of women infected with syphilis than found in earlier studies suggests that sexually transmitted diseases are circulating in the general population and highlights the increasing importance of HIV prevention.

Adolescent↗

Induction of swine dysentery in swine by the intravenous injection of filtered Treponema hyodysenteriae.

Swine dysentery was induced in 18 swine exposed by intravenous injection of a filtrate which contained Treponema hyodysenteriae and was obtained from macerated colonic scrapings of swine dysentery. However, swine dysentery did not develop in swine injected intravenously with a pure culture of T. hyodysenteriae or when combined with a colonic filtrate from normal swine. Diarrheal feces from the swine injected intravenously with the filtered T. hyodysenteriae contained more mucus, and fecal smears contained more T. hyodysenteriae and fewer other bacteria than did swine exposed orally to colon infected with swine dysentery or filtered T. hyodysenteriae. In the colons of the 12 swine injected intravenously with filtered T. hyodysenteriae that died, there was a minimum amount of croupous membrane and, microscopically, the T. hyodysenteriae were located deep in the colonic crypts. Five of the six surviving swine injected intravenously with filtered T. hyodysenteriae developed serum anti-T. hyodysenteriae antibodies using the indirect fluorescent antibody test and four of these swine developed diarrhea when reexposed with swine dysentery infected colon six weeks after initial exposure. None of the swine injected intravenously with cultured T. hyodysenteriae developed serum anti-T. hyodysenteriae antibodies and all were highly susceptible to swine dysentery.

Animals↗