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Inhibition of macrophage C3b-mediated ingestion by syphilitic hamster T cell-enriched fractions.

Macrophages are important for host defense against syphilitic infection. Our results show that C3b-mediated ingestion (C3bMI), a characteristic of activated macrophages, was inhibited in vitro by nonadherent cells from hamsters infected with Treponema pallidum subspecies endemicum. When macrophage target cells from normal, syphilitic, or lipopolysaccharide-treated animals were co-cultured with nonadherent cells derived from normal or syphilitic hamsters, noticeable differences were detected. Nonadherent syphilitic cells significantly suppressed macrophage C3bMI, whereas normal nonadherent cells displayed little or no suppressive activity. In general, macrophage C3bMI was reduced by nonadherent cells obtained throughout the course of syphilitic infection, although it eventually began to recover. The syphilitic nonadherent cells with maximum suppressive effect were those obtained from hamsters infected for 3 to 6 wk. The addition of treponemal antigens additionally inhibited C3bMI. The inhibitory effect of syphilitic nonadherent cells on either lipopolysaccharide-treated or syphilitic macrophages was sustained even when the nonadherent cells were removed from the cultures, and the effect continued for at least 72 hr thereafter. Fractionation of syphilitic nonadherent cell populations by two independent methods produced T cell-enriched preparations with significantly more suppressive activity than non-T cell-enriched preparations. These observations may account for the chronicity of syphilitic infection.

Adult↗

The molecular diagnosis of cutaneous infection.

Molecular biologic techniques are having an impact on many different aspects of medicine. In the realm of infectious agents, they are enhancing our diagnostic capabilities, allowing earlier detection of infection, avoiding the need of culturing infectious agents for the purpose of diagnosis, and broadening our concepts to include the presence of infection in the absence of a culturable agent or serologic evidence of infection. As one might expect, the applicability of these techniques varies with the type of infectious agent being considered. For example, in most bacterial infections the infectious agent can be cultured and accurately identified within 48 hours. It is therefore unlikely that molecular diagnostic techniques will replace the "gold standard" of culture in instances of bacterial infection. Mycobacterial and spirochetal agents, by contrast, do not fall into this category. Although the rapid growers (Mycobacterium fortuitum and Mycobacterium chelonae) pose little problem because they can be cultured within 1 week, M. tuberculosis, M. leprae and the slow growing mycobacteriae require long intervals to culture and/or identify. These organisms may in the future be identified with molecular diagnostic techniques. In the group of spirochetal pathogens, Treponema pallidum infection is, for the most part, easily diagnosed with serologic studies. In early seronegative cases, spirochetes can be detected in primary inoculation lesions by darkfield microscopy or in tissue sections with appropriate stains. Conversely, detection of Borrelia burgdorferi is currently fraught with difficulties. Tissue sections stained for these spirochetes are difficult to interpret, and serologic studies have shown widely variable results. The polymerase chain reaction has already been applied to the study of Borrelia infection with encouraging early results.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Development of shuttle vectors for spirochetes.

Constructions of Escherichia coli-spirochete shuttle vectors are based on naturally occurring plasmids, broad host range plasmids or bacteriophages. This review primarily focuses on genetic tools for Treponema denticola which is associated with periodontal diseases. The T. pallidum FlaA protein, E. coli beta-galactosidase, and the green fluorescent protein were successfully expressed in T. denticola from a shuttle vector system.

Flagellin↗

Sociodemographic dynamics and sexually transmitted infections in female sex workers at the Mexican-Guatemalan border.

BACKGROUND: If the predominant means of HIV transmission is heterosexual in the Soconusco region of Mexico, then the female sex workers (FSWs) from Central America who work in this region may be playing a significant role in the heterosexual transmission of HIV. GOAL: The goal was to estimate the prevalence of several sexually transmitted infections (STIs), including HIV infection, and to evaluate the population mobility of Mexican and Central American FSWs in the Soconusco region in Chiapas State, Mexico. METHODS: A cross-sectional study was conducted upon the construction of a sampling frame of sex work-related bars in the municipalities of the Soconusco region. Consenting participants answered a questionnaire that recorded sociodemographic characteristics, previous and current experience in commercial sex, and risk indicators for STI. Women also provided blood and endocervical swab specimens to be analyzed. RESULTS: A sample of 484 women were enrolled, who were characterized as follows: the average age was 25.6 years, and a high proportion had children, were single, had started sexual activity at an early age, and had a low level of education and low earnings. The global prevalences of infections with Treponema pallidum, HSV-2, HIV, Neisseria gonorrhoeae, and Chlamydia trachomatis were 9.4%, 85.7%, 0.6%, 11.6%, and 14.4%, respectively. Frequencies of HBcAb and HBsAg hepatitis B markers were 17.7% and 1.3%. The cumulative prevalence of treatable gonorrhea, chlamydia, and syphilis was 27.4%. CONCLUSION: The data on women's mobility illustrate that the Soconusco region attracts Central American women to enter the commercial sex trade. The women's sociodemographic characteristics were consistent with high prevalences of STI, except HIV infection. The low frequency of HIV infection suggests that this population may have had little contact with HIV core groups in Central America and in the Soconusco and no history of blood transfusion or intravenous drug use.

Adolescent↗

The outer membrane of Treponema pallidum: biological significance and biochemical properties.

Rabbits infected intravenously with Treponema pallidum were not markedly febrile, and the pyrogenicity of treponeme preparations administered intravenously to rabbits was negligible. The antibiotic polymyxin B did not induce any ultrastructural changes on the treponemal surface and was not lethal (immobilizing) for T. pallidum, which was, however, highly susceptible to detergents such as SDS. Extraction of treponemes with Triton X-100 removed the outer membrane (despite the presence of Mg2+) as shown by electron microscopy, and solubilized a limited number of proteins detectable by SDS-PAGE, including a dominant antigen (47 kDal) demonstrated by immunoblotting. None of the proteins were heat-modifiable. Periodic acid-silver staining of polyacrylamide gels for carbohydrate together with protease K digestion did not demonstrate major carbohydrate components in whole treponemes, or in the Triton-soluble fraction. Surface iodination of intact treponemes revealed very little surface exposure of treponemal proteins, although a protein which co-migrated with host albumin was labelled and appeared to be associated with the treponemal surface. Many treponemal proteins were, however, labelled when iodination was done in the presence of Triton. These observations, indicate that the outer membrane of T. pallidum differs significantly from those of many Gram-negative pathogens.

Animals↗

Evaluation of rosaramicin phosphate in treatment of experimental syphilis in rabbits.

The in vivo activity of rosaramicin phosphate in disseminated and localized Treponema pallidum infections in rabbits was compared with that of penicillin G benzathine. Rabbits were injected either intradermally or intravenously to establish infection. Groups of four animals each then received either two weekly injections of 200,000 U of penicillin G benzathine, injections of 12.5 or 25 mg of rosaramicin per kg of body weight twice a day for 10 days, or no antibiotic therapy. Treatment of the intradermal and intravenous infections was initiated on days 7 and 14 postinfection, respectively. With both infection models, striking differences were noted between the untreated control rabbits and the three groups receiving treatment; no discernible differences, however, were detected among any of the treated groups. Rabbits that had been infected intravenously did not develop disseminated lesions or orchitis after treatment, and chancres produced by intradermal infection regressed and healed rapidly after the initiation of therapy. Continued increases in treponemal and nontreponemal antibody titers posttreatment did not occur in any of the treated rabbits. Infectivity studies also suggested that the lymph nodes and testes of treated animals were free from infectious organisms. Overall, at the dosage regimens employed, both rosaramicin and penicillin G benzathine appeared to effect complete control of the experimental disease.

Animals↗

Comparison of the benzoyl-DL-arginine-naphthylamide (BANA) test, DNA probes, and immunological reagents for ability to detect anaerobic periodontal infections due to Porphyromonas gingivalis, Treponema denticola, and Bacteroides forsythus.

Most forms of periodontal disease are associated with the presence or overgrowth of anaerobic species that could include Treponema denticola, Porphyromonas gingivalis, and Bacteroides forsythus among others. These three organisms are among the few cultivable plaque species that can hydrolyze the synthetic trypsin substrate benzoyl-DL-arginine-naphthylamide (BANA). In turn, BANA hydrolysis by the plaque can be associated with periodontal morbidity and with the presence of these three BANA-positive organisms in the plaque. In this investigation, the results of the BANA test, which simultaneously detects one or more of these organisms, were compared with the detection of these organisms by (i) highly specific antibodies to P. gingivalis, T. denticola, and B. forsythus; (ii) whole genomic DNA probes to P. gingivalis and T. denticola; and (iii) culturing or microscopic procedures. The BANA test, the DNA probes, and an enzyme-linked immunosorbent assay or an indirect immunofluorescence assay procedure exhibited high sensitivities, i.e., 90 ot 96%, and high accuracies, i.e., 83 to 92%, in their ability to detect combinations of these organisms in over 200 subgingival plaque samples taken from the most periodontally diseased sites in 67 patients. This indicated that if P. gingivalis, T. denticola, and B. forsythus are appropriate marker organisms for an anaerobic periodontal infection, then the three detection methods are equally accurate in their ability to diagnose this infection. The same statement could not be made for the culturing approach, where accuracies of 50 to 62% were observed.

Bacteria, Anaerobic↗

Cerebral blood flow changes in general paresis following penicillin treatment: a longitudinal single photon emission computed tomography study.

Three cases of general paresis were successfully treated with high-dose penicillin. In all cases, cerebrospinal fluid cell counts decreased to normal and mental status improved rapidly. Cerebrospinal fluid protein concentrations decreased and IQ scores and overall levels of functioning improved gradually over 1 year. Regional cerebral blood flow (CBF) changes were analyzed longitudinally for 1 year using single photon emission computed tomography (SPECT). Autoradiography method and region of interest (ROI) analyses were used for quantitative CBF assessment and 3D stereotactic surface projections (3D-SSP) analyses were used for qualitative CBF pattern assessment. 3D-SSP could not reveal remarkable CBF pattern changes through the courses. The ROI analyses showed remarkable CBF decreases in all brain regions 1 month after the treatment, which recovered to normal levels 1 year after the treatment. These results suggest that remarkable decreases of quantitative CBF counts reflect the disappearance of encephalitis, while their gradual recovery reflects the gradual improvement of cerebral functional activity. As Treponema pallidum infection affects whole brain and CBF changes globally, quantitative CBF assessment may be more efficient than qualitative CBF pattern analyses for the purpose of understanding the pathophysiology of general paresis.

Brain↗

An evaluation of oligoclonal banding and CSF IgG index in the diagnosis of neurosyphilis.

It can be difficult to determine which patients would benefit from therapy to control central nervous system infection with Treponema pallidum. The authors have followed patients prospectively to evaluate two new diagnostic tests available. They performed lumbar punctures on 107 consecutive patients with syphilis of unknown duration, untreated (n = 19) or with serology that did not decrease sufficiently during follow-up (n = 88). The mean age was 47 years, with 91 males and 16 females. Twelve had neurologic symptoms. In order to establish a gold standard, the authors required the cerebrospinal fluid Venereal Disease Research Laboratory (CSF VDRL) test to be reactive (n = 25). They then examined oligoclonal banding and CSF IgG index as diagnostic tests by comparing them to the gold standard. Oligoclonal banding, abnormal in 20, had a sensitivity of 52% and a specificity of 91%. The CSF IgG index, abnormal in 56, had a sensitivity of 92% and a specificity of 60%. The posttest likelihoods of a positive test result were low, and hence neither test ruled in the diagnosis. With a post-test likelihood (PTL) negative of 4%, a negative CSF IgG index assisted in ruling out the diagnosis. Oligoclonal banding was not a satisfactory test for neurosyphilis. The CSF IgG index appears to help only in ruling out infection. Further effort is needed in developing diagnostic tests to assist the clinician in the diagnosis of neurosyphilis.

Electrophoresis, Agar Gel↗

Funisitis associated with leptospiral abortion in an equine placenta.

Funisitis, inflammation of the umbilical cord, is well recognized in human placentas. This report describes a case of funisitis associated with leptospiral infection in the placenta of a Thoroughbred foal born prematurely. The umbilical cord had diffuse superficial yellow discoloration along its entire length. Microscopic evaluation showed an exudate of neutrophils admixed with fibrin on the surface. Warthin-Starry staining showed spirochetes in the Wharton's jelly of the umbilical cord. A locally extensive, severe placentitis not involving the star and allantoic cystic hyperplasia were the other lesions observed in the allantochorion. Leptospira funisitis is similar to the funisitis of congenital syphilis in humans, although there are some major microscopic differences. In Leptospira funisitis, lesions were limited to the cord surface, whereas in lesions in human umbilical cords with Treponema pallidum infection, the changes are observed mostly around the vessels and in the Wharton's jelly.

Abortion, Veterinary↗

Spontaneous cytokine gene expression in normal guinea pig blood and tissues.

The authors report, for the first time, the cloning, characterization and sequencing of guinea pig cDNAs for interleukin (IL)-2, IL-10, IL-12p40, and transforming growth factor beta (TGF-beta). Partial cDNAs for two additional cytokines, IL-1alpha and TNF-alpha, whose sequences are present in the GenEMBL database, were also cloned. The IL-10 clone is a full-length cDNA, while the remaining clones are partial cDNAs. The guinea pig cDNA sequences have high identity with their mouse and human counterparts. Northern blot analysis revealed that the guinea pig transcripts range in size from 1.0 kb to 2.2 kb. The constitutive expression of cytokines in two strains of guinea pig (C4D, Albany) that differ in susceptibility to infection with Treponema pallidum was examined. Since susceptibility to T. pallidum is also age dependent, both neonates and adults were examined. Spontaneous cytokine expression was examined in peripheral blood, skin, spleen, lymph node, brain, and peritoneal cells. In skin, lymph node, and peripheral blood, very low levels of IL-1alpha, IL-12p40, tumour necrosis factor alpha (TNF-alpha), and TGF-beta and moderate levels of IL-2 and IL-10 were observed. Cytokine gene expression was not observed in spleen and brain. Peritoneal cells expressed only TGF-beta. Age- and strain-associated differences were not observed, except for IL-12p40, which was elevated in guinea pigs resistant to T. pallidum infection (C4D neonates, Albany adults).

Adult↗

Molecular diagnosis of syphilis: the Schaudinn-Hoffmann lymph-node biopsy.

Although serological tests are usually sufficient for the diagnosis of syphilis, they can be unhelpful in identifying the stage of Treponema pallidum infection in various situations. We used fine-needle aspiration of inguinal lymph nodes followed by PCR and Southern blotting to test for treponemal DNA in three patients with suspected secondary or latent syphilis. All three patients were positive by this technique. This approach could serve as a useful new tool for the diagnosis of syphilis in uncertain cases.

Biopsy, Needle↗

Seropositivity of the rapid plasma reagin (RPR) test in a dental school patient population: a retrospective study.

OBJECTIVES: The purpose of this retrospective study was to determine the seropositivity of the rapid plasma reagin (RPR) in a dental school patient population. METHODS: Blood was drawn on 20,844 subjects registering for treatment at the Louisiana State University School of Dentistry. All subjects who are admitted to the dental school are submitted to RPR screening (Macro-Vue-RPR Card, Becton Dickinson), blood indices, and serum chemistries. Venereal Disease Research Laboratory (VDRL), microhemagglutination assay for Treponema pallidum (MHA-TP) and/or fluorescent treponemal absorption test for Treponema pallidum (FTA-ABS) were also run on the positive RPR results. RESULTS: Two hundred seventy-nine (1.34%) of the 20,844 were RPR-positive. Sixty-two subjects (0.30%) of this total population from the RPR-positive findings were nonreactive (biological false positives or BFP) to the MHA-TP and FTA-ABS. This left 217 (1.04%) subjects of the 20,844 screened who were seropositive on both the RPR and the FTA-ABS or MHA-TP. CONCLUSIONS: Since this study has not been performed in a dental school patient population setting, comparison with other institutions is difficult. The authors agree that routine RPR testing is helpful and cost effective to detect patients possibly infected with Treponema pallidum in a large patient population.

Adult↗

Influence of cardiolipin antibodies on the binding of treponemal specific antibodies in the fluorescence treponemal antibody absorption test and the Treponema pallidum immobilisation test.

The aim of the present study was to investigate the biological role of cardiolipin antibodies during Treponema pallidum infection. Inhibition of the binding of treponemal specific antibodies at the early and late stages of infection by cardiolipin antibodies was shown in the fluorescence treponemal antibody absorption (FTA-ABS) test and T. pallidum immobilisation (TPI) test. Incubation of treponemes with cardiolipin antibodies followed by a second incubation with treponemal specific antibodies resulted in a reduction of the titres of the FTA-ABS test and the TPI test. The findings suggest that cardiolipin antibody production should be considered as a virulence mechanism of pathogenic treponemes with the purpose of evading the host defence mechanisms.

Animals↗

Association of oral spirochetes from sites of periodontal health with development of periodontitis.

The purpose of this investigation was to determine whether the presence of disease-associated bacteria in health-associated plaque correlated with susceptibility to periodontitis over time. Sites of periodontal health were identified in 65 adults. Six months later (recall 1), plaque was collected from sites that remained in periodontal health, and specific bacteria were detected using monoclonal antibodies in a microscopic assay. The spirochete morphogroup was identified by phase contrast microscopy. The relationship between detection at recall 1 and development of periodontitis over two successive 6-month intervals (recalls 2 and 3) was evaluated by means of logistic regression using generalized estimating equations (GEE), from which odds ratios (OR) were estimated and tested for significance. Significant relationships were defined as those having ORs with P < 0.05. Ninety-three of 1,032 sites developed signs of early periodontitis over the 12-month interval between recall 1 and recall 3. The spirochete morphogroup (OR = 3.13, P < 0.001) and pathogen-related oral spirochetes (PROS) (OR = 3.68, P < 0.001) were significantly associated with healthy sites that developed periodontitis. The association of Treponema socranskii was not significant (OR = 3.62, P = 0.0918). Odds ratios for Campylobacter rectus, Eikenella corrodens, and Porphyromonas gingivalis were less than 2.0 and not significant. Treponema denticola was not detected in health-associated plaque from stable health sites and was detected in only three sites that progressed to periodontitis. These findings indicate that the presence of PROS and some unidentified spirochetes in health-associated plaque is associated with increased susceptibility to periodontitis.

Adult↗

Spirochaetes and other bacterial species associated with bovine digital dermatitis.

The 16S rRNA genes from spirochaetes associated with digital dermatitis of British cattle were amplified by polymerase chain reaction from digital dermatitis lesion biopsies using one universal and one treponeme-specific primer. Two treponemal sequences were identified both of which shared a high degree of homology with the oral pathogen Treponema denticola (98%). Two further 16S rRNA gene sequences were obtained and shared similarity to Bacteroides levii (99%) and Mycoplasma hyopharyngis (98%). Polymerase chain reaction with T. denticola-specific primers amplified a potential virulence gene from digital dermatitis lesions which shared a high degree of homology to the 46-kDa haemolysin gene of T. denticola. The significance of the presence of organisms in digital dermatitis lesions of the bovine foot which are closely related to oral pathogens is discussed.

Amino Acid Sequence↗

[Malignant syphilis in human immunodeficiency virus infection].

INTRODUCTION: The associated infection with Treponema pallidum and human immunodeficiency virus (HIV) was responsible for the return of malignant syphilis. CASE REPORT: We report a case of malignant syphilis which revealed a HIV seropositivity. The lesions were typical. Serological features were in accordance with the diagnosis. A treatment with penicillin was prescribed and there was no relapse after five years. DISCUSSION: The diagnosis of malignant syphilis in a HIV positive patient may be difficult. The course of the disease may be serious and a prolonged treatment with high doses of penicillin is often necessary. The occurrence of the malignant syphilis in HIV positive patients is not fortuitous and seems to be related to an abnormal immunity.

AIDS-Related Opportunistic Infections↗

Genital ulcers in a primary health clinic in Rwanda: impact of HIV infection on diagnosis and ulcer healing (1986-1992).

During 1986-88 and 1990-92, 1025 (97%) out of 1057 genital ulcer patients in Kigali, Rwanda, were tested for HIV antibodies and for infection with Treponema pallidum, Haemophilus ducreyi and herpes simplex virus. Overall, 57% of men and 80% of women had antibodies to HIV-1. The most frequent laboratory diagnoses were chancroid (27%), syphilis (19%) and genital herpes (19%) among men and syphilis (35%), genital herpes (23%) and chancroid (20%) among women. HIV-1 seroprevalence increased sharply over time among men but not among women. The clinical presentation of ulcers as well as laboratory diagnoses were similar in the HIV-1 seropositive and seronegative groups. The relative frequency of all laboratory diagnoses remained unchanged over time. HIV-1 seropositivity had no impact on ulcer healing. Advanced immunodeficiency was diagnosed among 12% of the HIV-1 seropositive patients and was significantly associated with increasing age and genital herpes.

AIDS-Related Opportunistic Infections↗