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PubMed1999

Coiling phagocytosis is the predominant mechanism for uptake of the colonic spirochetosis bacterium Serpulina pilosicoli by human monocytes.

Serpulina pilosicoli is a newly identified pathogenic spirochete that establishes persistent colonic infections in human beings and animals. Macrophages are one of the key defenses against invasion of mucosal surfaces by bacterial pathogens. Macrophages engulf many bacteria by conventional phagocytosis; however recent studies indicate coiling phagocytosis as a new and important mechanism for internalization of Legionella pneumophila and spirochetes of the genus Borrelia, Leptospira, and Treponema. In this study, THP-1 human monocytic cells were incubated with the human S. pilosicoli strain SP16 and the contribution of coiling and conventional phagocytosis to the total number of phagocytic events were determined by sequential ultrastructural examination between 5 and 45 minutes. The frequency of phagocytosis increased over time from 5.1% after 5 minutes up to 21.9% after 45 minutes with greater than 70% of the events involving coiling phagocytosis. The data indicate that coiling phagocytosis may be a universal mechanism for uptake of pathogenic spirochetes.

Brachyspira↗
PubMed2001

Dendritic cells phagocytose and are activated by Treponema pallidum.

Cell-mediated immune processes play a prominent role in the clinical manifestations of syphilis, a sexually transmitted disease of humans caused by spirochetal bacterium Treponema pallidum. The immune cell type that initiates the early immune response to T. pallidum thus far has not been identified. However, dendritic cells (DCs) are the first immune-competent cells to encounter antigens within skin or mucous membranes, the principal sites of early syphilitic infection. In the present study, immature DC line XS52, derived from murine skin, was utilized to examine T. pallidum-DC interactions and subsequent DC activation (maturation). Electron microscopy revealed that T. pallidum was engulfed by DCs via both coiling and conventional phagocytosis and was delivered to membrane-bound vacuoles. The XS52 DC line expressed surface CD14 and mRNA for Toll-like receptors 2 and 4, molecules comprising important signaling components for immune cell activation by bacterial modulins. Both T. pallidum and a synthetic lipopeptide (corresponding to the 47-kDa major membrane lipoprotein) activated the XS52 DC line, as indicated by the secretion of interleukin-12 (IL-12), IL-1beta, tumor necrosis factor alpha, and IL-6 and elevated surface expression of CD54. The combined data support the contention that DCs stimulated by T. pallidum and/or its proinflammatory membrane lipoproteins are involved in driving the cellular immune processes that typify syphilis.

Animals↗
PubMed2000

Evaluation of rapid diagnostic tests for the detection of human immunodeficiency virus types 1 and 2, hepatitis B surface antigen, and syphilis in Ho Chi Minh City, Vietnam.

An evaluation of three new rapid diagnostic test kits for human immunodeficiency virus types 1 and 2 (HIV-1/2), hepatitis B surface antigen (HBsAg), and syphilis involved a two-phase comparison of rapid diagnostic assays using prospectively collected from hospitals and clinics in Ho Chi Minh City, Vietnam. After specificity and sensitivity testing, three new rapid diagnostic test kits were tested in parallel with six commonly used diagnostic test kits. The Determine HIV-1/2 test had fewer indeterminate or equivocal results than the Capillus HIV-1/HIV-2 or HIV Blot 2.2 tests. However, the Determine HIV-1/2 test yielded one false-positive result when compared with the Serodia HIV, HIV Blot 2.2, and microparticle enzyme immunoassay (IMx) HIV tests. The Serodia HBsAg test yielded more false-negative results when compared with the Determine HBsAg diagnostic test kit. The results of the syphilis diagnostic tests evaluated in this clinical trial consistently agreed with those of the rapid plasma reagin test for syphilis. The Determine Syphilis Treponema pallidum (TP) test had three false-positive results compared with the Serodia TP and the Serodia TP x particle agglutination (PA) tests, which had two false-positive results that were confirmed as negative by an ELISA. Application of these serologic tests within this comparative evaluation framework, using the World Health Organization alternative testing strategies, proved to be an effective way to determine serostatus related to HIV, hepatitis B, and syphilis.

Evaluation Studies as Topic↗
PubMed2007

Phagocytosis of Borrelia burgdorferi and Treponema pallidum potentiates innate immune activation and induces gamma interferon production.

We examined the interactions of live and lysed spirochetes with innate immune cells. THP-1 monocytoid cells were activated to comparable extents by live Borrelia burgdorferi and by B. burgdorferi and Treponema pallidum lysates but were poorly activated by live T. pallidum. Because THP-1 cells poorly internalized live spirochetes, we turned to an ex vivo peripheral blood mononuclear cell system that would more closely reflect spirochete-mononuclear phagocyte interactions that occur during actual infection. In this system, B. burgdorferi induced significantly greater monocyte activation and inflammatory cytokine production than did borrelial lysates or T. pallidum, and only B. burgdorferi elicited gamma interferon (IFN-gamma) from NK cells. B. burgdorferi was phagocytosed avidly by monocytes, while T. pallidum was not, suggesting that the enhanced response to live B. burgdorferi was due to phagocytosis of the organism. When cytochalasin D was used to block phagocytosis of live B. burgdorferi, cytokine production decreased to levels comparable to those induced by B. burgdorferi lysates, while the IFN-gamma response was abrogated altogether. In the presence of human syphilitic serum, T. pallidum was efficiently internalized and initiated responses resembling those observed with live B. burgdorferi, including the production of IFN-gamma by NK cells. Depletion of monocytes revealed that they were the primary source of inflammatory cytokines, while dendritic cells (DCs) directed IFN-gamma production from innate lymphocytes. Thus, phagocytosis of live spirochetes initiates cell activation programs in monocytes and DCs that differ qualitatively and quantitatively from those induced at the cell surface by lipoprotein-enriched lysates. The greater stimulatory capacity of B. burgdorferi versus T. pallidum appears to be explained by the successful recognition and phagocytosis of B. burgdorferi by host cells and the ability of T. pallidum to avoid detection and uptake by virtue of its denuded outer membrane rather than by differences in surface lipoprotein expression.

Borrelia burgdorferi↗
PubMed2004

[Direct detection of Treponema pallidum in diagnosis of syphilis].

Available methods for direct diagnosis of syphilis are summarized with emphasis being on those promising for routine use. Direct detection of the causative agent T. pallidum is limited since the agent is not able to synthesize enzyme cofactors, fatty acids and nucleotides de novo, is completely dependent on its host and thus culture on synthetic media is not feasible. Direct diagnosis of syphilis is based on rabbit infectivity testing (RIT), dark field or fluorescent microscopy and recently also on molecular biological methods used with increasing frequency in routine practice. Suitability and usability of different methods for direct detection of T. pallidum at different stages of syphilis are explained. Except for molecular biological methods, most of detection techniques can only be used at the primary and secondary stages or in early congenital syphilis. Major PCR methods for diagnosis of syphilis are presented. Not all of them are suitable for use in routine practice owing to differences in their sensitivity and design. The polA PCR method appears to be the most promising in this regard.

Animals↗
PubMed2006

Local oxygen therapy for treating acute necrotizing periodontal disease in smokers.

BACKGROUND: The main aim of treatment for acute necrotizing periodontal disease is fast and effective reduction of anaerobic destructive microorganisms to avoid periodontal damage. The effect of adjunctive local oxygen therapy in the treatment of necrotizing periodontal disease was examined in this study. METHODS: Thirty patients with acute necrotizing periodontal disease were treated with the systemic antibiotics amoxicillin, clavulanic acid, and metronidazole. In 15 out of 30 patients, adjunctive local oxygen therapy was administered. The patients were followed from the first to 10th day of treatment with clinical and bacteriological examinations. The clinical examination registered gingival bleeding, periodontal probing depth, and attachment loss; to follow up microbiological colonization of the periodontal sulcus, five representative bacteria were registered by a semiquantitative DNA polymerase chain reaction test. RESULTS: In both groups of patients, colonization with Prevotella intermedia, Tannerella forsythensis, and Treponema denticola was initially positive. None of these three microorganisms were completely eradicated in any of the patients in the group without oxygen therapy within the first 10 days of treatment. In the group with adjunctive oxygen therapy, all patients either showed a reduction in or complete eradication of the microorganisms, resulting in more rapid clinical restitution with less periodontal destruction. CONCLUSIONS: Adjunctive oxygen therapy results in early eradication of pathogenic anaerobic microorganisms in cases of acute necrotizing periodontal disease. The damage to periodontal tissue is reduced.

Acute Disease↗
PubMedDate not supplied

Sexually transmitted diseases: risks, transmission, and laboratory diagnostic update.

Sexually transmitted diseases (STDs) are a major public health problem of the 1990s. In the pre-antibiotic era, these infections were often fatal. The 1960s saw an alteration in public attitudes toward sexual practices and a resultant increase in the incidence of STDs. Today, despite increased efforts in health education and the encouragement of "safe sex" practices, the incidence of STDs continues to rise. Infection control is complicated by the frequent lack of symptoms of many STDs. This article will discuss only the most common STDs in the United States. These include those caused by the organisms Neisseria gonorrhoeae, Herpes simplex virus, Chlamydia trachomatis, Treponema pallidum, Haemophilus ducreyi, and Hepatitis B virus.

Cytodiagnosis↗
PubMed1989

Characterization of lipid-modified immunogenic proteins of Treponema pallidum expressed in Escherichia coli.

This study describes the sequence of the immunodominant Treponema pallidum surface protein TpD and its expression in Escherichia coli. The translated TpD DNA sequence revealed the presence of a putative site for lipid-modification downstream from the signal sequence of this membrane protein. Growth of TpD-expressing E. coli in the presence of radioactive palmitic acid revealed that TpD was lipid-modified. Three other, previously characterized cloned proteins of T. pallidum were also lipid-modified. The N-termini of two of three sequenced T. pallidum proteins contain a tetrapeptide sequence characteristic for lipoproteins in Gram-negative bacteria: Leu-X-Y-Cys. Only TpD differed from this consensus sequence in the substitution of the first residue by Phe. The apparent high incidence of lipoproteins among E. coli recombinants expressing T. pallidum antigens suggest an important role of lipoproteins in the induction of humoral immunity during syphilitic infection.

Amino Acid Sequence↗
PubMed1989

Evaluation of Western immunoblotting technique in the serological diagnosis of human syphilitic infections.

Purified human syphilitic antibodies against both 15.5 Kd and 45 Kd treponemal antigens appear T. pallidum specific and do not cross react with antigens possessed by other treponemes (T. phagedenis, T. hyodysenteriae and a human intestinal treponeme). By using Western immunoblotting technique, 107 out of 110 syphilitic patients and 291 out of 294 subjects with serologically positive diagnostic tests for syphilis were found to have in their sera antibodies against a 15.5 Kd specific antigen of T. pallidum. These antibodies were present in 100% of the patient with secondary or early latent syphilis, both untreated and treated, in 98.24% of those with late latent treated syphilis and in 100% of patients with neurosyphilis. On the contrary, they were absent in 47 patients with false positive reactions for syphilis and in 121 healthy blood donors. For these reasons, the demonstration of these kind of antibodies in a patient's serum can be considered of high value in differentiating syphilitic patients from non infected individuals.

Antibodies, Bacterial↗
PubMed1995

Poor correlation between reactive syphilis serology and human immunodeficiency virus testing among potential cornea donors.

PURPOSE: The current practice in which eye banks screen cornea donors for syphilis is based mainly on the potential utility of positive syphilis serology as a surrogate marker for human immunodeficiency virus-1 (HIV-1) infection. We examined the correlation between positive syphilis and HIV-1 serologies within the potential cornea donor population. METHODS: We distributed a questionnaire to 94 eye banks in the United States regarding their rates of positive serology for syphilis and HIV-1 between Feb. 1 and July 30, 1992. We subsequently used the polymerase chain reaction for HIV-1 to further evaluate the whole blood of 21 rapid plasma reagin and fluorescent treponemal antibody-positive, HIV-1 enzyme-linked immunosorbent assay (ELISA)-negative cornea donors to determine whether these donors were infected with HIV-1 but were within a seronegative window for HIV-1 antibodies at their time of death. RESULTS: Of 8,932 donors screened, 103 (1.15%) had reactive screening for syphilis serology and 35 (0.39%) were HIV-1 seropositive. No donor with positive syphilis serology was also HIV-1 seropositive. Twelve of 31 donors who originally tested seropositive for syphilis by nontreponemal screening tests (Venereal Disease Research Laboratory or rapid plasma reagin tests) proved seronegative for syphilis when further tested with a treponemal test (FTA-ABS or microhemagglutination-Treponema pallidum), suggesting a high (38.7%) false-positive rate for the syphilis screening tests. Additionally, all 21 rapid plasma reagin and fluorescent-treponemal antibody-positive, HIV-1 ELISA-negative donors further tested were also negative for HIV-1 by the polymerase chain reaction. CONCLUSIONS: Among potential cornea donors, a population prescreened for identifiable HIV-1 risk factors, positive syphilis serology appears to be a poor marker for HIV-1 infection. The role of syphilis screening of potential cornea donors may need to be reevaluated.

AIDS Serodiagnosis↗
PubMed1978

Isolation of Treponema hyodysenteriae from sources other than swine.

Fecal samples were collected from animals and environments on 3 swine farms and cultured for Treponema hyodysenteriae. Each farm was a farrow-to-finish operation and, at the time of sampling, swine dysentery was enzootic among 8- to 22-week-old pigs. Pathogenic T hyodysenteriae was isolated from pigs on all 3 farms. On farm A, nonpathogenic T hyodysenteriae was isolated from a sample of lagoon water. On farm B, pathogenic T hyodysenteriae was isolated from a waste-holding pit. On farm C, a dog was observed to be eating feces of pigs that had swine dysentery. The dog was diarrheic and a fecal sample yielded a pathogenic isolant of T hyodysenteriae. Further isolation attempts were unsuccessful after the dog was removed from the infected premises. Isolation of pathogenic and nonpathogenic organisms from waste-holding systems emphasizes the need for cultural techniques in detecting pathogenic T hyodysenteriae.

Animals↗
PubMed1992

HIV prevalence in patients with sexually transmitted diseases in Yaounde, (Cameroon) in 1989 and 1990: necessity of an STD control programme.

OBJECTIVE: To monitor HIV seroprevalence among STD clinic attenders as part of a sentinel surveillance programme. DESIGN: Seroepidemiological survey on randomly selected patients. SETTING: "Elig Essono" STD clinic, Yaounde; from February 1989 to December 1990. PATIENTS: 1161 randomly selected patients. MAIN OUTCOME MEASURES: HIV and syphilis seroprevalence. RESULTS: Twenty six of the 1161 patients (2.4%; CI: 95%; 1.5%-3.3%) tested were found to be HIV positive (mostly due to HIV1); 35.4% had antibodies to Treponema pallidum. There was no association between HIV seropositivity and sex, marital status, or educational level. Genital ulcer disease did not correlate with HIV seroprevalence. However, patients with a positive serological test for T pallidum were more likely to have HIV infection (rr = 2.4; 95% CI; from 1.1 to 3.0). Results from 1990 were double those of 1989 (3.3% versus 1.6%, p = 0.02). CONCLUSIONS: Compared with the findings among the same groups in metropolitan areas of various other African countries, the HIV seroprevalence is still low; this could be due to many reasons, such as the recent introduction of the virus in the country, a different spectrum of STDs, the high level of circumcision of males. HIV infection trends should continue to be monitored among risk groups such as STD patients and control programmes implemented to reduce the rapid spread of AIDS in the country.

Adolescent↗
PubMed2005

Lipoprotein-dependent and -independent immune responses to spirochetal infection.

In this study, we used the epidermal suction blister technique, in conjunction with multiparameter flow cytometry, to analyze the cellular and cytokine responses elicited by intradermal injection of human volunteers with synthetic analogs for spirochetal lipoproteins and compared the responses to findings previously reported from patients with erythema migrans (EM). Compared with peripheral blood (PB), lipopeptides derived from the N termini of the Borrelia burgdorferi outer surface protein C and the 17-kDa lipoprotein of Treponema pallidum (OspC-L and 17-L, respectively) elicited infiltrates enriched in monocytes/macrophages and dendritic cells (DCs) but also containing substantial percentages of neutrophils and T cells. Monocytoid (CD11c(+)) and plasmacytoid (CD11c(-)) DCs were selectively recruited to the skin in ratios similar to those in PB, but only the former expressed the activation/maturation surface markers CD80, CD83, and DC-SIGN. Monocytes/macrophages and monocytoid DCs, but not plasmacytoid DCs, displayed significant increases in surface expression of Toll-like receptor 1 (TLR1), TLR2, and TLR4. Staining for CD45RO and CD27 revealed that lipopeptides preferentially recruited antigen-experienced T-cell subsets; despite their lack of antigenicity, these agonists induced marked T-cell activation, as evidenced by surface expression of CD69, CD25, and CD71. Lipopeptides also induced significant increases in interleukin 12 (IL-12), IL-10, gamma interferon, and most notably IL-6 without corresponding increases in serum levels of these cytokines. Although lipopeptides and EM lesional infiltrates shared many similarities, differences were noted in a number of immunologic parameters. These studies have provided in situ evidence for a prominent "lipoprotein effect" during human infection while at the same time helping to pinpoint aspects of the cutaneous response that are uniquely driven by spirochetal pathogens.

Adolescent↗
PubMed1998

The significance of syphilis serology tests on long-term hemodialysis patients.

BACKGROUND: Syphilis is a sexually transmitted disease. Blood transfusion and blood contact are also routes of infection. Patients on long-term hemodialysis are at risk during their therapy. The aim of this study is to investigate the incidence of syphilis in hemodialysis patients, possible nosocomial infection and methods of treatment. MATERIALS AND METHODS: A total of 556 uremic patients on maintenance hemodialysis at our hospital on June 1996 were enrolled in the study. They all received syphilis screening tests. The rapid plasma reagin (RPR) test was used as the primary screening tests and Treponema pallidum hemagglutination assay (TPHA) test as the confirmation test. According to the test results, patients were classified into false and true-positive groups. The titer of both tests were recorded. The patients in the true-positive group were further divided into the untreated and treated group depending on whether they had already received treatment. The serial change of RPR test titer of the treated group was reviewed. RESULTS: Thirty-one patients (5.6%) had positive RPR test results and 10 patients (1.8%) had false-positive results. The titers of both RPR and TPHA tests were rather low in the positive groups. Most of the confirmed syphilis patients were asymptomatic and diagnosed serologically. In the treated group, the RPR test titer did not show significant decline and no seroconversion was noted after treatment. CONCLUSION: We observed that infectious syphilis patients exist in our hemodialysis unit and survey for this disease is necessary. The titers of both positive RPR and TPHA tests are low. Most diagnosed patients had latent syphilis, and serologic response to treatment is probably the same as in general population.

Aged↗
PubMed1999

Sequence conservation of glycerophosphodiester phosphodiesterase among Treponema pallidum strains.

Previous investigations have demonstrated that immunization with Treponema pallidum subsp. pallidum glycerophosphodiester phosphodiesterase significantly protects rabbits from subsequent treponeme challenge. In this report, we show that the glycerophosphodiester phosphodiesterase amino acid sequence is conserved among 12 strains from a total of five pathogenic treponemes. The invariant nature of this immunoprotective antigen makes it an attractive candidate for inclusion in a universal subunit vaccine against T. pallidum infection. In addition, these studies show a silent nucleotide substitution at position 579 of the gpd open reading frame which is consistently observed in the non-T. pallidum subsp. pallidum strains. This sequence alteration introduces a PleI restriction site in the nonsyphilis strains and thus allows genetic differentiation from T. pallidum subsp. pallidum strains.

Animals↗
PubMed1985

Cellular and extracellular protein antigens of Treponema pallidum synthesized during in vitro incubation of freshly extracted organisms.

A new medium that permits radiolabeling of freshly extracted cells of Treponema pallidum with [35S]methionine very efficiently has been devised. Although treponemes were not purified free of contaminating rabbit tissue, label was incorporated exclusively into treponemal protein in a linear manner for at least the first 16 h of in vitro incubation. Throughout this period, virtually a full complement of treponemal proteins was synthesized, based on a sodium dodecyl sulfate-polyacrylamide gel electrophoresis comparison of the radiolabeled protein profile with the Coomassie blue-stained profile of gradient-purified treponemes. The radiolabeled protein profiles obtained with three pathogenic strains were very similar but not identical. Using solubilized treponemal extracts and a sensitive radioimmunoprecipitation procedure, we identified the protein antigens of T. pallidum that were recognized by immunoglobulin G antibodies in various rabbit and human syphilitic sera. A simple fractionation procedure has been used to separate soluble and membrane-bound treponemal proteins. A number of the membrane proteins are exposed on the cell surface, since intact radiolabeled treponemes bound antibodies directed against these proteins. In addition, a unique class of low-molecular-weight extracellular treponemal proteins has been identified. The cell surface-exposed proteins were among the earliest proteins recognized by immunoglobulin G antibodies after experimental infection of rabbits with T. pallidum.

Animal Population Groups↗