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[Current status of vaccine development in sexually transmissible diseases].

A prophylactic vaccine represents a major hope for the control of sexually transmitted diseases. The current general vaccine strategies and the status of vaccine development against infections with Neisseria gonorrhoeae, Treponema pallidum, Chlamydia trachomatis and Herpes simplex virus are described. Vaccines consisting of whole infectious agents are replaced by protective subunits. A subunit vaccine has the advantage to be free from other components, which are not relevant for protection and which may confer unwanted side effects. At the present time vaccine development against infections with Neisseria gonorrhoeae and Herpes simplex virus seems to be the most progressed. With monoclonal antibodies several surface components could be identified, which are of importance for the pathomechanism. With Treponema pallidum and Chlamydia trachomatis the development is delayed by unsolved problems of immunity. For the production of vaccines molecular-biologic methods, like protein synthesis or gene-cloning will be used. Genetically modified live vaccines or polytope hybrid vaccines will gain importance in the future.

Humans↗

Treponemal infection in a Pleistocene bear.

The age and origins of the organisms that cause syphilis (treponemes) have long been matters for controversy. The widely-held belief that Columbus's ship brought the disease from the New World to Europe rests on identification of the classic lesions in Inca, Aztec and Mississippian bones that date from 1,000 to 3,000 years before present. But these were not confirmed by immunological techniques. We have observed lesions characteristic of treponemal infection in a Pleistocene bear from Indiana (dated 11,500 years BP) which give a positive result when tested with the antisera used by the US Center for Disease Control for verification of syphilis infection. This is the earliest detection of treponemal disease using contemporary techniques.

Animals↗

Treatment of latent syphilis in HIV-infected patients with 10 d of benzylpenicillin G benethamine: a prospective study in Maputo, Mozambique.

Neurosyphilis has been reported in HIV-infected patients previously treated with penicillin G benzathine, which does not achieve treponemicidal levels in cerebrospinal fluid. Therapy combining benzylpenicillin G and its repository form benzylpenicillin G benethamine could be a potentially effective alternative enhanced regimen for treating latent syphilis in HIV-infected patients because peak serum and cerebrospinal fluid concentrations would be achieved early post-administration by the former molecule and sustained for 24 h due to the prolonged half-life of the latter. In this study, 23 asymptomatic HIV and Treponema pallidum co-infected patients received 10 d of combined therapy (2 M IU intramuscular once daily) and were followed up at 3, 6 and 12 months. None experienced side effects or clinical symptoms. Of the 18 patients who were evaluated 1 y later, 8 (44.4%) exhibited serological treatment failure, defined as a positive serum rapid plasma reagin test. In conclusion, a 10-d regimen combining penicillin G and penicillin G benethamine seems to be of no benefit compared to currently recommended treatment.

Adult↗

Interleukin-8 and granulocyte elastase in gingival crevicular fluid in relation to periodontopathogens in untreated adult periodontitis.

BACKGROUND: This study aimed to determine the relationships among interleukin (IL)-8 and granulocyte elastase levels in gingival crevicular fluid (GCF) and the concomitant presence of periodontopathogens in untreated adult periodontitis. METHODS: GCF and subgingival plaque samples were collected from 16 patients with untreated adult periodontitis and 10 healthy control subjects. IL-8 levels were determined by enzyme-linked immunosorbent assay (ELISA). Granulocyte elastase was analyzed with a neutrophilic granulocyte-specific, low molecular weight and chromogenic substrate, L-pyroglutamyl-L-prolyl-L-valine-p-nitroanilide, and the maximal rate of elastase activity (MR-EA) was calculated. Five DNA probes were used to detect the presence of A. actinomycetemcomitans (A.a.), B. forsythus (B.f.), P. gingivalis (P.g.), P. intermedia (P.i.), and T. denticola (T.d.). RESULTS: Lower IL-8 concentrations and higher granulocyte elastase activities were found in patients than in healthy controls as well as in diseased conditions co-infected with B.f., P.g., P.i., and T.d. as compared to healthy conditions without the target species (P <0.05). IL-8 concentrations were positively correlated with MR-EA levels in the periodontitis conditions co-infected with B.f., P.g., P.i., and T.d. (P <0.05). A wide range of IL-8 concentrations was found among 15 patients when the periodontitis condition was characterized by co-infection with B.f., P.g., P.i., and T.d. MR-EA levels in the high IL-8 group of subjects were significantly higher than those in the low IL-8 group of subjects (P <0.01). CONCLUSIONS: The present study shows that the local host-bacteria interactions in untreated periodontitis are diverse in terms of the intensity of inflammatory responses measured by IL-8-related granulocyte elastase activity in GCF. This might reflect different phases of the inflammatory response due to shifts in host-bacteria interactions and therefore be indicative of a range of periodontal disease activity levels.

Actinobacillus Infections↗

Treponemal infections in hares in The Netherlands.

Treponemal infections in wild European brown hares (Lepus europaeus) from The Netherlands were diagnosed by means of serological tests for human syphilis and histological demonstration of spirochetes by the Bosma-Steiner silver impregnation method in histological sections of skin lesions. The treponeme should probably be classified as "Treponema paraluisleporis."

Animals↗

Immune complexes in experimental syphilis: a methodologic evaluation.

Sustained antigenic stimulation following intravenous infection of rabbits with Treponema pallidum results in antibody responses and the formation of immune complexes. Complexes in greater than 300 sera from normal rabbits and from animals with experimental syphilis were measured by Raji cell and polyethylene glycol-complement consumption assays. Profound increases in both the incidence and levels of immune complexes were seen between the third and seventh weeks of infection. Single radial immunodiffusion studies revealed moderate increases in immunoglobulin levels and depression of C3 levels during the third and fourth weeks of infection. Penicillin treatment was followed by normalization of C3 levels and clearance of immune complexes. Lower levels of complexes in the sera of intradermally infected rabbits and the absence of immune complexes in intratesticularly infected animals suggest that immune complexes in the circulation may be related to the extent and severity of cutaneous involvement.

Animals↗

In vitro antimicrobial activity against reference strains and field isolates of Treponema hyodysenteriae.

The in vitro susceptibilities of eight isolates of Treponema hyodysenteriae from pigs naturally infected with swine dysentery between 1976 and 1983 were determined by an agar dilution technique. Carbadox, olaquindox, tiamulin, metronidazole, furazolidone, and monensin were the most active against these field isolates regardless of the year of recovery. The influence of inoculum size on the MICs against four reference strains of T. hyodysenteriae was studied. Various degrees of activities of ampicillin and lincomycin were found, depending on the inoculum size. The effect of successive in vitro subcultures on the susceptibility of a reference strain of T. hyodysenteriae was examined. The strain resistant to tylosin became susceptible to the drug.

Anaerobiosis↗

Demonstration and immunochemical characterization of natural, autologous anti-idiotypic antibodies throughout the course of experimental syphilis.

Immunoglobulin Gs (IgGs) from serial bleeds obtained 1 week to 5 months after infection of rabbits with Treponema pallidum were examined for autologous anti-idiotypic (auto-anti-Id) antibodies. The capacities of IgGs to bind 125I-IgG F(ab')2 anti-T. pallidum prepared from earlier bleeds were determined by using radioimmunoassays. Results obtained in these assays suggested that auto-anti-Id IgGs were demonstrable between 60 and 180 days postinfection. Following reinfection, 90 days after the initial infection, auto-anti-Id IgGs peaked 6 to 8 weeks later, even though they were first noted as early as 2 weeks postreinfection. In the reinfection model the auto-anti-Id continued to persist throughout the remaining 3 months of the study. As auto-anti-Id antibodies to anti-fibronectin antibodies were demonstrable also in reinfected animals, our findings raise questions concerning the possible role of the anti-Id in modulating the Id expression of both T. pallidum-specific and autoimmune humoral responses.

Animals↗

Immune abnormalities in guinea pigs with asymptomatic congenital syphilis.

Spleens from 1-20-wk-old guinea pigs infected in utero with Treponema pallidum and age-matched controls, born to normal and heat-killed (56 degrees C, 2 h.) T. pallidum-injected mothers, were examined for their in vitro lymphoproliferative response to phytohemagglutinin, concanavalin A, and lipopolysaccharide. Additionally, T cell surface markers (mu-chain, pan T, CD4, and CD8) were determined in spleen, lymph node, and peripheral blood from 10-wk infected and normal pups by single and dual parameter fluorescence-activated cell sorter analysis. Compared with control animals, congenitally infected animals showed a remarkable prolonged naive-type of immune response as reflected by the higher (p < 0.01) proliferative responses to both T cell mitogens (up to 20 wk of age), and the weaker response to the B cell mitogen, significantly different (p < 0.01) at 10 wk of age. As opposed to controls, in all organs examined the level of CD8+ (cytotoxic/suppressor) T cells was significantly diminished (p < 0.01); consequently, the CD4/CD8 ratio was significantly elevated (p < 0.05). The role of C4 complement component and the nature and potential role of the immature T and B lymphocyte responses in asymptomatic congenital syphilis is discussed.

Animals↗

[Pre- and perinatal infections with sexually transmissible microorganisms].

The sexually transmissible pathogenic microorganisms, which are also capable of initiating pre- or perinatal infections, include Neisseria gonorrhoeae, Treponema pallidum, Chlamydia trachomatis serovars D through K, group B streptococci, urogenital mycoplasmas, herpes simplex viruses types I and II, cytomegalovirus, hepatitis B virus, human immunodeficiency viruses, human papillomaviruses, Candida spp. and Trichomonas vaginalis. With special emphasis on paediatric and neonatological aspects, brief discussions of the following topics are presented: the epidemiology of these agents, the diseases they can induce in pregnancy, the mode of infection of and the diseases in the fetus and neonate, the preventive measures, the diagnosis and therapy.

Bacterial Infections↗

A novel pattern of treponemal antibody distribution in isolated South American Indian populations.

Serologic surveys for treponemal disease were carried out in 1970-1976 among three linguistically distinct and isolated population groups in the Brazilian Amazon Region and among the Mapuche Indians of southern Chile. Three patterns were found: 1) no evidence for treponemal infection in two very recently contacted groups; 2) sporadic positive individuals in groups with long periods of contact with non-Indian populations; and 3) a high prevalence of positive tests in one cultural group with limited exposure to non-Indians. The seroepidemiology and clinical manifestations of a possible treponemal infection in those villages with a high prevalence of positive tests were unlike those of the classically described human treponematoses.

Adolescent↗

The occurrence of treponemes in contagious ovine digital dermatitis and the characterisation of associated Dichelobacter nodosus.

Contagious ovine digital dermatitis (CODD) is a recently recorded, apparently new infection of the ovine hoof, which differs clinically from footrot caused by Dichelobacter nodosus and which fails to respond well to accepted treatment practices for footrot. Despite the welfare implications of such an infection, very little research has been performed on CODD to date and the aetiology remains confused. Suggestions have been made that there is a potential role for treponemes in the pathogenesis of CODD but that D. nodosus is apparently not involved. Six farms were therefore targeted in this study to provide a more in-depth investigation into the bacterial flora of CODD lesions. Dark ground microscopy, culture and PCR techniques were used, concentrating on the presence of D. nodosus and spirochaetes, particularly those of the genus Treponema. The results demonstrated that isolates of D. nodosus were indeed present in a high percentage (74%) of CODD lesions compared with 31% of apparently healthy feet. The isolates were shown to be of similar virulence type to those reported previously in cases of footrot, and the range of serogroups was also found to be similar to footrot, with serogroup H being prevalent. Treponemes were present in 70% of CODD lesions and 38% of apparently healthy feet, supporting a possible association between CODD and treponemes. However, any further progress on the aetiology of CODD and the potential for novel, effective treatment will depend on an improved ability to culture these organisms routinely in the laboratory thereby enabling their complete characterisation.

Animals↗

Intracellular location of Treponema pallidum (Nichols strain) in the rabbit testis.

During investigations designed to obtain purified suspensions of virulent Treponema pallidum (Nichols strain), infected rabbit testicular tissue was routinely examined in the electron microscope. Morphologically typical T. pallidum were found intracellularly within the cytoplasmic substance of fibroblasts, interstitial and Leydig cells, and of spermatocytes. The importance of these observations to latency and treatment is discussed.

Animals↗

Experimental syphilis in guinea pig.

The infrequent use of guinea pig in experimental syphilis, the not well genetically and immunologically characterized strains of animals originating from places with unspecified conditions of husbandry, and the various strains of Treponema pallidum used for infection provided inconsistent and discouraging results. For eight decades the rabbit has been the major animal model in studies of syphilis. However, the lack of readily available inbred strains of rabbits--necessary for adoptive transfer experiments--has been a stumbling block in revealing the mechanisms responsible for immunity, susceptibility, and resistance to T. pallidum infection. These difficulties have recently been overcome by demonstration of inbred strains susceptible to T. pallidum infection, paving the way to studies of adoptive immunity. The guinea pig may also be a better model than the rabbit for immunomanipulations (irradiation, injection with antibodies specific to various cell populations), allowing a closer insight into the immunopathologic mechanism operating during the course of syphilitic infection. The "rediscovery" of the guinea pig as a model for experimental syphilis and recent years of intensive studies justify a review summarizing older data and providing the most recent information. The authors, having first-hand experience with this model, will provide detailed information on (1) historical background; (2) course of infection with T. pallidum in inbred and outbred strains of guinea pigs; (3) the ID50 for various strains; (4) various routes of infection; (5) age and sex-dependent susceptibility to infection; (6) kinetic of the humoral response to specific and non-specific treponemal antigens; (7) appearance of autoantibodies and immune complexes; (8) cellular response, including lymphoproliferative response, macrophage inhibitory factor(s) production, chemotaxis and adoptive transfer of immunity by purified T cells; and (9) a complete list of references.

Animals↗

Intraoral dissemination of treponemes after periodontal therapy.

Oral treponemes are related to chronic periodontitis, but the effect of periodontal therapy on the majority of treponemal species is unknown. The aim of this prospective study was to evaluate the dynamics in prevalence profiles of treponemes in different habitats of the oral cavity. Thirty-five patients with chronic periodontitis were randomly assigned to mechanical debridement alone (control group) or systemic amoxicillin/metronidazole plus chlorhexidine (test group). Subgingival and mucous membrane plaque samples were taken at baseline, after 10 days, and during supportive periodontal therapy at 3, 6, 9, 12, 18, and 24 months. T. denticola, T. lecithinolyticum, T. maltophilum, T. socranskii, T. vincentii, and treponemal phylotypes I-VII were detected using polymerase chain reaction (PCR) and dot blot analysis. For the majority of the assessed treponemes, a significant intragroup increase in prevalence in the different habitats ( P<0.05) occurred over the study course but, compared to debridement alone, adjunctive antimicrobial therapy resulted in a nonsignificant trend toward lower prevalence in the subgingival habitat. In no case were treponemes eradicated from the oral cavity. After both therapies, possibly new infection with and/or dissemination of Treponema ssp. occurred, which led to treponemes recovering in different habitats and to increased intraoral prevalence. The prescribed adjunctive antimicrobial therapy may limit this increase in the subgingival region.

Amoxicillin↗

Treponemal phospholipids inhibit innate immune responses induced by pathogen-associated molecular patterns.

Host innate immune responses to microbial components, known as pathogen-associated molecular patterns (PAMPs), are regulated and modified by cellular receptors and serum proteins, including Toll-like receptors (TLRs), CD14, and LPS-binding protein (LBP). We demonstrated that a treponemal membrane lipid inhibited PAMPs-induced immune responses. The chemical structure of the lipid was elucidated as a phosphatidylglycerol (PG) derivative, which is scarce in most mammalian tissues, but relatively abundant in treponemal membrane lipids. Natural and synthetic PG counterparts as well as related natural anionic phospholipids, phosphatidylinositol, phosphatidylserine, and cardiolipin, also demonstrated an inhibitory effect. Further, we noted that PG inhibited PAMPs-induced immune responses by blocking the binding of PAMPs with LBP and CD14. In addition, PG decreased proinflammatory cytokine production in serum of LPS-injected mice and depressed abscess formation in mice infected with treponemes. These results suggest that treponemal phospholipid interfere the function of LBP/CD14 and act as a modulator of innate immune responses.

Abscess↗

The effect of parenteral immunisation on antibody production in the pig colon.

Local and systemic antibody production was studied in pigs to compare responses to live and killed bacterial antigen and purified protein antigen, with and without prior mucosal stimulation. Recovery from challenge with live bacteria and intramuscular injection with killed bacteria gave rise to similar high levels of serum IgG antibody, but the ratio of specific IgA to IgG in the colon was significantly higher after infection than following vaccination with killed bacteria. Vaccination with a protein antigen gave rise to serum and local antibody production. Prior feeding of the antigen had a tolerising effect on the serum antibody response, but production of IgG and IgA antibody by the colon was not suppressed.

Animals↗