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Inability of immune cells treated with anti-thymocyte serum to confer on hamsters resistance to cutaneous infection with Treponema pertenue.

The mechanism by which hamsters acquire resistance to yaws or frambesia is poorly understood. This investigation has shown that immune lymphoid cells (spleen and lymph node) could confer on hamsters resistance to infection with Treponema pertenue. Treatment of these immune cells with a specific antithymocyte serum (ATS) inhibited the transfer of resistance. Twenty-one days after infection, recipients of immune cells treated with ATS had cutaneous lesions, in contrast to recipients of immune cells treated with normal rabbit serum. Treatment of immune cells with ATS, however, did not completely abolish resistance to treponemal infection. The weight and number of treponemes in the lymph nodes of recipients were significantly lower than those infused with normal cells treated with ATS or normal rabbit serum. The specificity of the ATS was demonstrated by its failure to inhibit functional antibody-producing cells and its high cytotoxic activity for thymocytes. These results present direct evidence that ATS-sensitive cells are involved in resistance to frambesial infection.

Animals↗

The ability of peripheral blood mononuclear cells of rabbits infected with Treponema pallidum to produce IL-2.

It was previously found that the cell-mediated immune response involved in protection against Treponema pallidum is distinctly suppressed during some periods in the course of syphilis infection in rabbits. This may be a result of the weak ability of cells to produce Interleukin-2 (IL-2) as well as of IL-2 absorption. The ability of peripheral blood mononuclear cells (PBMC) of syphilitic rabbits to produce IL-2 develops within the first two weeks after infection reaching a maximum in about the eleventh week. In infection of longer duration, this capability was distinctly lowered. This low level of activity (no higher than in PBMC of normal rabbits) was maintained for 31 weeks. The ability of PBMC to absorb IL-2, in parallel with its production, was found at the same time in the course of syphilis infection (7-11 weeks). In long-lasting syphilis (more than 12 weeks) both abilities seem to be inhibited. Sera of syphilitic rabbits were found to have a higher level of IL-2 inhibitor than those of normal rabbits. Only in syphilis lasting 9 to 11 weeks, when the production of IL-2 was the greatest, was the level of IL-2 inhibitor nearly the same as in normal rabbit sera. In syphilis lasting longer, the increased level of inhibitor was accompanied by a decreased ability of cells to produce IL-2. These findings suggest that IL-2 inhibitor may be bound to IL-2 or IL-2 receptor on T lymphocytes and in this way would lead to weakening of T cell function and resistance against Treponema pallidum infection.

Absorption↗

Syphilis and HIV infection.

Treponema pallidum and HIV are both sexually transmitted agents of infectious diseases with epidemiological similarities. Ulcerous genital diseases such as primary syphilis facilitate transmission of HIV. An increasing number of case reports gives evidence that in HIV-infected patients secondary syphilis runs a more severe course and may present as syphilis maligna and that neurological complications of secondary and tertiary syphilis seem to occur more frequently and at an earlier stage. The clinical evaluation, interpretation of serology and choice of treatment schedules must take these considerations into account.

HIV Infections↗

Cell-mediated immunity in Treponema pallidum infected rabbits: in vitro response of splenic and lymph node lymphocytes to mitogens and specific antigens.

Peripheral blood lymphocytes from Treponema pallidum infected rabbits respond poorly to mitogen and specific antigens when cultured in the presence of autologous serum. Reactivity of lymphocytes from the spleen and popliteal lymph nodes of T. pallidum infected rabbits have therefore been examined by lymphocyte transformation using the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A) and extracts of T. pallidum. Spleen cell populations, both T cell enriched (by nylon wool elution) and non-nylon wool treated, which respond to T. pallidum as early as ten days post infection in normal serum, were suppressed in responses to T. pallidum when cultured in autologous serum. The same lymphocytes responded normally to PHA and Con A. Lymph node cells from infected rabbits responded normally to both T. pallidum antigen and mitogens in either autologous or normal rabbit serum. These data indicate that splenic lymphocytes are sensitive to regulatory factors in autologous serum during the early stages of T. pallidum infection whereas lymph node cells are not.

Animals↗

Effect of irradiation and depletion of C3-complement component on the course of Treponema pallidum infection in a resistant guinea pig strain.

The role of complement and ionizing radiation in the natural resistance to Treponema pallidum infection of Albany guinea pigs was explored. Depletion of C3 by cobra venom factor for a period of 14 days affected neither the host's susceptibility to infection nor the humoral response. Total body irradiation with 420 or 800 R was fatal within 20-30 days and there was no multiplication of treponemes in the infected host. Animals showing lethal signs were euthanized and tissues removed for examination. Exposure to a nonlethal dose of 300 R increased the susceptibility to infection (46% symptomatic lesions) and facilitated multiplication of treponemes at the site of inoculation and in the lymphoid organs, but the humoral response was not different from that of non-irradiated controls. The results seem to suggest a defect in antigen recognition by the immunocompetent cells in the resistant Albany guinea pigs.

Animals↗

Chronicity of infection with Treponema paraluis-cuniculi in New Zealand white rabbits.

Popliteal lymph nodes from eight New Zealand white rabbits with clinical or serological evidence of naturally acquired infection with Treponema paraluis-cuniculi were transferred to rabbits that had not been exposed to this infection. Lymph nodes from two rabbits successfully transmitted infection. The nodes from one of these rabbits transmitted infection during both the acute and chronic stages of infection. Recipients that were successfully infected showed concomitant antibody responses in the Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), and fluorescent treponemal antibody-absorption (FTA-ABS) tests six to 10 weeks after inoculation; recipients of uninfected nodes showed no change in serological state. Antibody responses were followed by the development of dark field positive genital lesions 14 to 15 weeks after inoculation.

Animals↗

HIV, HBV, delta-agent and Treponema pallidum infections in two rural African areas.

In order to compare the seroepidemiology of human immunodeficiency virus (HIV), hepatitis B virus, delta agent and Treponema pallidum infections in two rural populations living in north Uganda (Kitgum district) and in central Burundi (Butezi, Ruyigi region), 448 sera were tested for HBS-Ag, HBS-Ab, and anti-HIV antibodies and screened for syphilis using the T. pallidum haemagglutination (TPHA) test. HBS-Ag positive sera were also tested for anti-delta antibodies. Overall seropositivity rates in healthy subjects, outpatients and inpatients (non-AIDS) were 14.2% and 9.5% in Kitgum district and Butezi, respectively. The prevalence of HBS-Ag and HBS-Ab ranged from 10.0% to 15.6% and from 66.2% to 68.9%, respectively. In north Uganda the rates of anti-delta positivity were 3.1% in the overall population and 30.6% in the HBS-Ag positive subjects. No serum obtained in Butezi was anti-delta positive. In Ugandan people, 64.0% of anti-HIV positive and 25.8% of anti-HIV negative patients were also TPHA-positive (P less than 0.01). For Butezi the corresponding figures were 21.4% and 1.6% respectively (P less than 0.04). On the contrary, no correlation was found between either anti-HIV or TPHA positives and seropositivity for B and delta hepatitis serological markers. The study demonstrated an association between seropositivities for HIV and T. pallidum (TPHA), suggesting common patterns of transmission. On the contrary, no association seemed to exist between HBV and HIV infections.

Adult↗

Light and electron microscopy of rabbit testes infected with Treponema pallidum (Nichols strain): nature of deposited mucopolysaccharides and localisation of treponemes.

The mucopolysaccharide nature of the material deposited in rabbit testes infected with Treponema pallidum was confirmed by histochemical staining with alcian blue. Differential staining of mucopolysaccharides showed the presence of sulphated mucopolysaccharides as an almost constant feature, whereas in little more than half of the orchitic testes studied variable deposits of hyaluronic acid were seen. The treponemes were almost exclusively present in the areas rich in mucopolysaccharide. A combination staining with the Warthin-Starry method and alcian blue showed treponemes in close association with pre-existing fibrils and cells contained in these fibrils. The latter findings were confirmed by electron microscopy, and the fibroblasts to which treponemes adhered displayed the characteristics of activated cells. The close parallel between the histopathological changes observed here and their descriptions in published reports shows that our specific strain still behaves the same as the original Nichols pathogenic strain of T pallidum.

Animals↗

Detection of nonspecific resistance to Listeria monocytogenes in rabbits infected with Treponema pallidum.

Several lines of evidence suggest that cell-mediated immunity (CMI) is suppressed in the early stages of infection caused by Treponema pallidum and becomes activated at the time that latency is induced. In the studies reported in this paper, rabbits were infected intravenously with T. pallidum and subsequently challenged with Listeria monocytogenes. Enhanced ability to suppress the growth of Listeria was detected in their livers between 3 and 5 weeks after infection with T. pallidum, corresponding to the onset and regression of the generalized syphilitic eruption. A second infection of T. pallidum 4 weeks after the first, at a time when suppression was beginning to wane, prolonged the listericidal activity. These observations support the hypothesis that infection by T. pallidum stimulates CMI, which, in turn, may play a role in inducing latency.

Animals↗

New evidence for the non-infectivity of Treponema pallidum for mice.

We have recently shown that syphilitic rabbits are resistant to challenge with Listeria monocytogenes. This resistance was thought to reflect stimulation of cell-mediated immunity by active infection with Treponema pallidum. We now report data which show that the growth of Listeria was not suppressed in mice inoculated with T. pallidum. Re-inoculation with T, pallidum or with a large dose of an avirulent treponeme also failed to suppress the growth of Listeria. These results contrast with those obtained in rabbits and provide additional evidence that T. pallidum is not infective for the mouse.

Animals↗

Enzyme-linked immunospot assay for the diagnosis of active Treponema pallidum infection during the various stages of syphilis.

BACKGROUND: Specific serologic assays for syphilis cannot differentiate current infections from past infections and are inefficient to monitor efficacy of antibiotic therapy. GOAL: To develop a new immunologic assay for the identification of active Treponema pallidum infection during the various stages of syphilis. STUDY DESIGN: Peripheral blood mononuclear cells obtained from patients with syphilis in an STD clinic were tested for T. pallidum-specific circulating antibody-secreting cells (ASC) by an enzyme-linked immunospot assay (ELISPOT). RESULTS: Specific ASC were demonstrated in all six patients with primary syphilis and in 14 of 16 patients diagnosed with secondary syphilis. ASCs were undetectable in five patients 8 to 16 days after appropriate therapy, but persisted in one case that was considered treatment failure. Among the 13 patients diagnosed with latent syphilis, six (46%) demonstrated ASC, reflecting antigenic stimulation. CONCLUSION: The ELISPOT assay is effective for the diagnosis of primary and secondary syphilis. The presence of circulating ASC suggests persistent active infection in some patients during the latent disease stage.

Adolescent↗

In utero infection with Treponema pallidum in early pregnancy.

Amniocentesis was performed under sonographic guidance in gravidas (< 20 weeks' gestation) with untreated syphilis. Five to ten millilitres of amniotic fluid from each patient was used for rabbit infectivity testing (RIT) and polymerase chain reaction (PCR) to detect amniotic fluid infection with Treponema pallidum. Gravidas were treated with benzathine penicillin G. Newborns were examined for clinical and laboratory signs of congenital syphilis including immunoglobulin M (IgM) antibody to T. pallidum by Western blotting (immunoblotting). Eleven patients were enrolled at a mean gestational age of 16.8 weeks. T. pallidum was recovered from amniotic fluid by RIT in four cases (36 per cent), and PCR was positive in three of the amniotic fluid specimens (27 per cent). There were no false-positive PCR results. None of the newborns had clinical evidence of congenital syphilis and their sera lacked IgM reactivity to T. pallidum antigens by immunoblotting. These findings confirm in utero infection with T. pallidum in continuing early pregnancy and indicate that in utero treponemal infection can be eradicated by maternal treatment.

Adolescent↗

Host response to Treponema pallidum infection. I. Quantitative changes of lipids in rabbit organs.

Levels of phospholipids, glycolipids and cardiolipin were determined in various organs of Treponema pallidum-infected rabbits. The phospholipid levels on the second week of infection decreased significantly in the spleen but remained unchanged in other organs. During the same time, glycolipids decreased significantly in both kidney and heart. 3 days after infection, a brief but significant increase of cardiolipin in the spleen was observed. Heat-killed T. pallidum but not Treponema reiteri caused a similar effect. The possible implication of these changes in the immunopathology of syphilis is discussed.

Animals↗

Lymphocyte transformation in inbred guinea pigs infected with Treponema pallidum nichols.

T lymphocytes were purified from peritoneal exudates from young male, inbred strain 2 guinea pigs infected with 8 X 10(7) Treponema pallidum Nichols and from control animals injected with normal rabbit testes extract. Groups of animals were sacrificed after 15, 30, 60, and 90 days of infection, and the cells were analyzed for their proliferative response to concanavalin A and phytohemagglutinin and to sonicated T. pallidum, Treponema phagedenis biotype Reiter, and normal rabbit testes extract. No significant differences were observed in the responses to mitogens. Cells from infected but not from control animals responded with significant proliferation to T. pallidum antigen, but neither infected nor control cells reacted to T. phagedenis Reiter antigen. Although cells from both infected and control animals responded to normal rabbit testes extract, this response in the infected animals was transient and much lower than the response to T. pallidum antigen.

Animals↗

Frequent and preferential infection of Treponema denticola, Streptococcus mitis, and Streptococcus anginosus in esophageal cancers.

Multiple cancers frequently occur in the upper digestive tract. One possible explanation is that specific bacterial infection stimulates the normal epithelium to initiate inflammation and/or promotes carcinogenesis. This study was undertaken to determine which bacterial species is predominantly associated with esophageal cancer. We examined the bacterial diversity in this type of cancer and in the saliva from healthy people by using a culture-independent molecular method. Here we report the preferential and frequent infection of the oral periodontopathic spirochete Treponema denticola (T. denticola), Streptococcus mitis (S. mitis), and Streptococus anginosus (S. anginosus) in esophageal cancer from different regions of the world, and we also describe the induction of inflammatory cytokines by infection of S. anginosus and S. mitis. Our present data suggest that these three bacteria could have significant roles in the carcinogenic process of many cases of esophageal cancer by causing inflammation and by promoting the carcinogenic process, and that eradication of these three bacteria may decrease the risk of recurrence.

Blotting, Northern↗

Testing umbilical cords for funisitis due to Treponema pallidum infection, Bolivia.

To establish the frequency of necrotizing funisitis in congenital syphilis, we conducted a prospective descriptive study of maternal syphilis in Bolivia by testing 1,559 women at delivery with rapid plasma reagin (RPR). We examined umbilical cords of 66 infants whose mothers had positive RPR and fluorescent treponemal antibody absorption tests. Histologic abnormalities were detected in 28 (42%) umbilical cords (seven [11%] had necrotizing funisitis with spirochetes; three [4%] had marked funisitis without necrosis; and 18 [27%] had mild funisitis), and 38 [58%] were normal. Of 22 umbilical cords of infants from mothers without syphilis (controls), only two (9%) showed mild funisitis; the others were normal. Testing umbilical cords by using immunohistochemistry is a research tool that can establish the frequency of funisitis due to Treponema pallidum infection.

Antibodies, Bacterial↗