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An experimental model of early central nervous system syphilis.

Although up to 40% of patients with early syphilis have evidence of central nervous system (CNS) invasion by Treponema pallidum, the pathogenesis of CNS syphilis is not understood. A rabbit model that mimics early CNS involvement in humans was developed and characterized. Mild cerebrospinal fluid pleocytosis was evident 2 weeks after intracisternal inoculation of T. pallidum and peaked at 9 weeks. The VDRL test in cerebrospinal fluid was reactive in 24% of animals, most commonly at 9 weeks after infection. T. pallidum could be isolated from the CNS of animals infected for 4, 6, or 9 weeks but not from animals infected for 12 or 20 weeks. Clinically, 6% of animals developed uveitis, similar to the frequency in patients with secondary syphilis. Thus, this model of meningeal and ocular syphilis seems to be analogous to the early CNS infection in humans and can be used for studies of pathogenesis and treatment.

Animals↗

Correlation between detection rates of periodontopathic bacterial DNA in coronary stenotic artery plaque [corrected] and in dental plaque samples.

Utilizing PCR, the 16S rRNA detection rates for Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Treponema denticola, and Campylobacter rectus in samples of stenotic coronary artery plaques were determined to be 21.6, 23.3, 5.9, 23.5, and 15.7%, respectively. The detection rates for P. gingivalis and C. rectus correlated with their presence in subgingival plaque.

Aggregatibacter actinomycetemcomitans↗

Induction of de novo subcortical actin filament assembly by Treponema denticola major outer sheath protein.

Treponema denticola and its major outer sheath protein (Msp) induce actin reorganization in fibroblasts. We adapted a barbed-end labeling/imaging assay to monitor Msp-induced subcortical actin filament assembly in neutrophils and fibroblasts. Msp, at an actin-reorganizing concentration, inhibited migration of these dissimilar cell types, whose cytoskeletal functions in locomotion and phagocytosis are crucial for immunity and healing of peripheral infections.

Actin Cytoskeleton↗

Comparison of profiles of key periodontal pathogens in periodontium and endodontium.

Despite the established anatomical relationship between the periodontal and pulpal tissues, bacterial migration between endodontium and periodontium is still under discussion. The objective of this study was an investigation of profiles of periodontal pathogens in pulpal and periodontal diseases affecting the same tooth by means of 16S rRNA gene directed polymerase chain reaction (PCR). 31 intact teeth with both pulp and marginal infections were investigated. The diagnosis was based on clinical and radiological examination. Samples were taken from the gingival sulcus or periodontal pocket, respectively, with sterile paper points before trepanation of the teeth. After trepanation sterile paper points and Hedstroem files were used for taking samples from the root canal. Specific PCR methods were used to detect the presence of the following pathogens: Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Eikenella corrodens, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola. In addition, quantitative competitive PCR was used to determine the total bacterial count of the samples. The investigated pathogens were proven to be present in the endondontium in all disease categories. Particularly in endodontic samples of "chronic apical periodontitis" and "chronic adult periodontitis" profiles of the periodontal pathogens were found. The results confirmed that periodontal pathogens often accompany endodontic infections and supported the idea that the periodontic-endodontic interrelationships should be considered as critical pathways which might contribute to refractory courses of endodontic or periodontal diseases.

Adult↗

Herpesviral-bacterial interactions in aggressive periodontitis.

BACKGROUND: Human cytomegalovirus, Epstein-Barr virus and herpesvirus co-infections occur with significantly higher frequency in actively progressing than in stable periodontitis sites of adolescents and young adults. Also, periodontal presence of cytomegalovirus and Epstein-Barr virus is associated with increased occurrence of subgingival Porphyromonas gingivalis, Bacteroides forsythus, Dialister pneumosintes, Prevotella intermedia, Prevotella nigrescens, Treponema denticola and Actinobacillus actinomycetemcomitans. AIM: This article reviews the evidence linking herpesviruses to the development of aggressive periodontitis and suggests a potential mechanism for herpesviral acceleration of the periodontal disease process. CONCLUSIONS: It seems to be a reasonable supposition that the etiopathogenesis of various types of aggressive periodontitis includes the combined action of herpesviruses and specific bacterial species. New vaccines and vaccination technologies that are being developed against herpesviruses warrant testing for their ability to induce a protective immune response against destructive periodontal disease. Clearly, the importance of combined herpesviral-bacterial infections and associated host responses in the development of periodontitis needs to be studied further.

Adolescent↗

Electron microscopy of Treponema pallidum (Nichols) cultivated in tissue cultures of Sf1Ep cells.

The in vitro interaction between Treponema pallidum and Sf1Ep cells during treponemal replication was investigated by using transmission electron microscopy. The Sf1Ep cells grown on Teflon-treated cover slips after 12 days of cocultivation were fixed in situ, overlaid with agar, embedded, and vertically sectioned. Large numbers of treponemes were found extracellularly not only at the upper cell surfaces but also in the narrow spaces between the cells and between the cells and the cover slips. These narrow spaces supported treponemal growth and survival, as did those at the upper cell surfaces. Although few in number, organisms were also seen in cell vacuoles either surrounded by a membrane or free in the cytoplasm. Some extracellular treponemes attached to host cells by body spirals or the terminal end and formed electron-dense layers at attachment sites. Some treponemes were often surrounded with amorphous, extracellular material which appeared to "connect" them to host cell surface. After 12 days of cocultivation, host cells showed excessive vacuolation and appeared to be damaged. This did not seem to be due to treponemal infection alone, because cells from uninfected cultures also showed similar vacuolation.

Animals↗

[Systematic serologic detection of treponema at the antivenereal centre of the National Institute of Public Health in Abidjan (Côte-d'Ivoire), from 1994 to 1999].

We conducted a medical records review on 11,662 patients consulting the antivenereal clinic of Treichville from 1994 to 1999. The main objective of the study was to analyse the data from systematic screening of syphilis in this specialized centre for sexual transmitted infection. The results of this study were: 162 (1.39%) patients had active syphilis; we noticed a decreasing incidence of syphilis during the last six years, 98.77% of the patients had symptoms of sexual transmitted diseases that did not directly evoke syphilis. In summary we can say that syphilis remains an important problem in the sexually transmitted infections consultation. The screening of syphilis must continue and needs to be extended to other services, because of the high frequency of asymptomatic forms and the existence of severe complications.

Adolescent↗

[The impact of HIV infection on the incidence of syphilis and gonorrhea at a university hospital (1985-1994)].

Syphilis and gonorrhea are two sexually transmitted diseases (STD) which still persist in spite of the existence of effective treatment. In this paper the incidence of these two diseases was evaluated between 1985-1994, a decade during which the problem of HIV infection arose. Every patient who attended the STD Program at the Hospital and was suspected of having syphilis and/or gonorrhea was clinically evaluated and was subjected to the following tests: a) search for Neisseria gonorrhoeae (Ng) and penicinilase producers (PPNG) identification, b) search for Treponema pallidum (Tp) by darkfield microscopy, c) serological studies for syphilis. From 1985 to 1991 the average of positive cases for Ng was 14.8% while from 1992 to 1994 it was 4.0% (p < 0.0001) showing a dramatic decrease between 1991 and 1992. PPNG increased from 8.7% in 1985 to 44.6% in 1988 and then slowly decreased down to 26.9% in 1994. From 1985 to 1990 the average of positive darkfield examinations was 20.7% while from 1991 to 1994 it was 12.2% (p < 0.0001). Between 1985 to 1988 syphilis serological studies showed 45.7% positive cases dropping to 34.3% between 1989 and 1994 (p < 0.0001). HIV infection appearance had a wide repercussion throughout the world generating behavioral and sexual habit changes which have probably helped to prevent these two STD. Gonorrhea incidence was also influenced by the appearance of new effective treatments, even against PPNG, such as fluorated quinolones and third generation cephalosporines. The population studied belongs to the most crowded area in Argentina, so that these observations should not be extrapolated to the rest of the country.

Adolescent↗

An unexpected result in an evaluation of a serological test to detect syphilis.

Traditional tests for detection of syphilis are labour intensive and costly. Enzyme immunoassays (EIAs) are readily automated and cost effective if large numbers of tests are performed. Four experiments were devised to evaluate a syphilis EIA test kit where resources are limited: (1) testing antenatal patients; (2) testing refugees; (3) testing a high prevalence population; and (4) testing "problem sera" (containing autoantibodies or antibodies to other infective agents). Forty-one available syphilitic sera from antenatal patients were tested to evaluate sensitivity. Specificity was determined through testing sera determined to be nonreactive with rapid plasma reagin and Treponema pallidum hemagglutination tests, calculating the sample size (456) on the confidence interval (CI) required. Two runs were performed on antenatal sera, giving sensitivities of 32% (95% CI: 20%, 47%) and 37% (95% CI: 24%, 52%) and specificities of 92% (95% CI: 89%, 94%) and 90% (95% CI 87%, 92%), respectively. We present a method to evaluate a serological test where resources are limited. Unexpectedly, the test kit performed poorly as a screening test. New serological tests need to be evaluated in-house prior to adoption.

Adult↗

Sexually transmitted diseases in Germany.

In the former West Germany, in specific venereal diseases legislation passed in 1953, only syphilis, gonorrhoea, ulcus molle, and lymphogranuloma venereum were defined as venereal diseases and subject to mandatory notification. The proportion of unreported cases was as high as 75% for syphilis and up to 90% for gonorrhoea. Epidemiological data for the past 10 years exist only on selected populations from research studies and are summarized in this article. In the former East Germany reporting of sexually transmitted infections (STIs) was mandatory and, due to the centralized organization, underreporting was considered to be low, although no specific studies have examined this. After the unification in 1990 of the two German states the West German laws were adopted in East Germany. Since 1982 - when the first AIDS case was reported in Germany - information on AIDS cases has voluntarily been collected at the national register at the AIDS Centre of the Robert Koch Institute in Berlin. The law governing the reporting of infectious diseases has recently been revised. Under the new Protection against Infection Act, which became effective on 1 January 2001, clinical diagnoses of STIs (with the exception of hepatitis B) are no longer notifiable diseases. Laboratory reporting of positive test results for Treponema pallidum has been introduced. With T. pallidum and HIV notifications, additional disaggregated data are collected. Since T. pallidum and HIV remain the only notifiable STIs, all other STIs have to be monitored through sentinel surveillance systems. These surveillance systems are currently being established. Under the new legislation, local health authorities have to provide adequate counselling and testing services for STIs, which may be provided free of charge if necessary.

Acquired Immunodeficiency Syndrome↗

Renaissance mummies in Italy.

The paleopathological study of 40 Italian Renaissance mummies has allowed us to perform about 20 diagnoses, of which 5 concern infectious (smallpox, hepatitis, condyloma, syphilis and pneumonia), 4 metabolic (obesity, atherosclerosis, gallstones and uric acid nephrolithiasis), 2 articular (DISH and rheumatoid arthritis) and 2 neoplastic (skin apithelioma and colon adenocarcinoma) diseases. The mummy of an anonymous child, dated back to the 16th century (C14=1569 +/- 60), presented a diffuse vesiculo-pustular exanthema. Macroscopic aspects and regional distribution suggested smallpox, while EM reavealed many egg-shaped, virus-like particles (250 x 50 nm), with a central dense core. Following incubation with anti-smallpox virus antiserum and protein A-gold complex immunostaining, the particles resulted completely covered with protein A-gold. These results clearly show that this Neapolitan child died of a severe form of smallpox some four centuries ago. The mummy of Maria of Aragon, Marquise of Vasto (1503-1568), reavealed on the left arm an oval, cutaneous ulcer (15x10 nm) with linen dressing. Indirect immunofluorescence with anti-treponema pallidum antibody identified a large number of filaments with the morphological characteristics of fluorescent treponemes. EM evidenced typical spirochetes, with axial fibril. These findings clearly demonstrate a treponemal, probably venereal, infection. The mummy of Ferrante I of Aragon, King of Naples (1431-1494), revealed an adenocarcinoma extensively infiltrating the muscles of the small pelvis. A molecular study of the neoplastic tissue evidenced a typical mutation of the K-ras gene codon 12:the normal sequence GGT (glycine) was altered into GAT (aspartic acid). At present this genetic change is the most frequent mutation of the K-ras gene in sporadic colorectal cancer. The alimentary "environment" of the Neapolitan court of the XV century, with its abundance of natural alimentary alkylating agents, well explains this acquired mutation. These and other diseases as, for example, a fatal puerperal complication, a thyroid goiter, a case of Wilson's cirrhosis, some cases of anthracosis and other peculiar traumatic conditions, such as a mortal stab-wound, can elucidate the pathocenosis of the wealthy classes of the Italian Renaissance.

History, 16th Century↗

Quantitative analysis of tpr gene expression in Treponema pallidum isolates: Differences among isolates and correlation with T-cell responsiveness in experimental syphilis.

Transcriptional analysis of the tpr genes in Treponema pallidum subsp. pallidum (referred to here as simply T. pallidum) has been limited to date, and yet the expression of members of this gene family is likely relevant to the pathogenesis of syphilis. Recently, immunological studies and semiquantitative mRNA analysis led to the hypothesis of the modulation of tpr gene transcription during infection and suggested that various strains of T. pallidum might differentially express these genes. In this study we developed a real-time amplification assay to quantify the tpr mRNAs with respect to the 47-kDa lipoprotein message and to compare transcript levels among four different strains of T. pallidum. In addition, we analyzed the lymphocyte responsiveness pattern toward the Tpr antigens in late experimental syphilis to identify tpr genes that had been expressed during the course of infection. The T-cell response has been implicated in clearance of treponemes from early lesions, and some of the Tprs were identified as strong targets of the cellular immune response. We show that message for many of the tpr genes can be detected in treponemes harvested at the peak of early infection. Interestingly, tprK seems to be preferentially expressed in almost every strain, and it is uniformly the target of the strongest cellular immune response. These studies demonstrate the differential expression of certain tpr genes among strains of T. pallidum, and further studies are needed to explore the relationship between tpr gene expression and the clinical course of syphilis in infected individuals.

Animals↗

Cloning and expression of Treponema pallidum (Nichols) antigen genes in Escherichia coli.

Hybrid pBR322 plasmid clone banks comprised of more than 125,000 recombinant DNA clones and representing the entire Treponema pallidum Nichols genome were constructed in Escherichia coli K-12 RR1. The two clone banks individually contain over 53,000 and 72,000 recombinant clones. The number average and mass average sizes of the cloned DNA inserts were found to be approximately 12 and 13 kilobase pairs, respectively, indicating the presence of large treponemal DNA inserts in a majority of recombinant clones. To detect E. coli clones synthesizing T. pallidum antigens as hybrid plasmid gene translation products in the clone bank, a simplified, direct, solid-phase radioimmuno-colony blot (RICB) assay was developed employing immunoglobulin G antibody isolated from anti-T. pallidum immune rabbit serum. Clones with positive reactivities in the RICB assay were isolated at frequencies of 0.1 to 0.2%. One isolated RICB-positive clone, designated RICB2-1, produced a very strong signal in the RICB assay and was subsequently found through E. coli cell-free in vitro transcription/translation analysis to encode the synthesis of two gene translation products with apparent molecular weights of 77,000 and 44,000. The 44,000-dalton protein was effectively immunoprecipitated from [35S]methionine-labeled E. coli clone cells by using either immune rabbit serum (preabsorbed with Treponema phagedenis biotype Reiter antigens) or selected human syphilitic serum, whereas the 77,000-dalton protein was never immunoprecipitable by similar methods. Purified plasmid DNA from clone RICB2-1 contained a treponemal DNA insert of 3.70 kilobase pairs, which was of suitable size to code for the 121-dalton (44 + 77) protein. The insert was also flanked on each end by PstI sites and possessed three internal PstI sites with fragment sizes of 2.15, 1.18, 0.20, and 0.17 kilobase pairs. Purified clone RICB2-1 plasmid DNA was capable of transforming recipient E. coli cells to virtually 100% RICB reactivity, thus substantiating the plasmid-encoded characteristic. Further experiments employing various antisera in radioimmunoprecipitation systems utilizing cell-free in vitro synthesized gene translation products from clone RICB2-1 also provided the first evidence that E. coli may be capable of using endogenous T. pallidum DNA promotors for genetic expression. These studies, amplified by the isolation of a potentially significant immunoprecipitable 44,000-dalton recombinant protein antigen, point to the importance of the "cloned antigen gene" approach for the eventual eludication of specific antigens or immunogens operative in the pathogenesis, immunology, and serodiagnosis of T. pallidum infection.

Antigens, Bacterial↗

Autoimmunity in syphilis.

The autoimmune response in natural and experimental syphilis, apparently triggered as a secondary reaction to T. pallidum infection, is represented by the production of various antibodies to self-antigens. In addition to the classic Wassermann (cardiolipin) antibodies, the following autoantibodies are associated with the disease: (1) biphasic hemolysin (known also as Donath-Landsteiner antibody), (2) antilymphocytic antibodies, (3) rheumatoid factor, (4) cryoglobulins, (5) antifibronectin, (6) anticollagen, (7) antilaminin, and (8) anticreatine kinase. Although less explored, the autoimmune reaction seems also to involve the cellular arm of the immune response. Transient sensitization of lymphocytes to homologous organ antigens have been reported in T. pallidum-infected rabbits. Questions of whether the humoral and cellular autoimmune responses--which are apparently harmless and of transient nature--play a role in immunoregulation and consequently affect the course of infection remain to be answered.

Animals↗

[In vivo study of the sensitivity of Treponema pallidum to ofloxacin].

Treponema pallidum has not been yet cultivated. Hence any in vitro investigation is excluded, and it is owing to the experimental animal model, the rabbit, that we have studied the susceptibility of that germ to ofloxacin. This quinolone, owing to its pharmacokinetic and therapeutic properties, can specially be indicated in the treatment of Sexually Transmitted Diseases. Thus, its appeared to be of the utmost importance to know if the suggested schedule of treatment for STD, might not be susceptible to modify the course of a co-existing incubating syphilis by either delaying or inhibiting the apparition of the clinical features of primary syphilis. This study was undertaken at the incubation period, in syphilitic rabbits, using kinetic data obtained in man, after a given dosage of ofloxacin. Results were appraised upon converging data: lesions, bacteriology, and serology of the tested lot compared with two control batches of infected rabbits, the first one being untreated, the other having received the reference antibiotic treatment. From the data obtained and in the experimental settled conditions where this study was done, it results that ofloxacin has no effect on the course of the experimental syphilitic infection.

Adolescent↗

Interaction of spirochetes with the host.

The success of an invading organism must depend on several cytoplasmic, surface-associated and secreted factors. The technical difficulties in handling pathogenic spirochetes like Treponema pallidum and Borrelia burgdorferi have made it difficult to define specific factors involved in entry and long-term survival. The problem of defining virulence factors has been attacked by several strategies: T. pallidum secretes a number of immunogenic low molecular mass proteins. The most predominant are of molecular weight 15.5 and 22 kDa. Preliminary data suggest that antibodies against these proteins induce protective immunity in rabbits experimentally infected with T. pallidum. Many potentially important surface-associated antigens of T. pallidum have now been cloned and characterized. Two of these, TpD and TpE, are lipoproteins which exhibit characteristic size heterogeneity. The apparent molecular weight of TpE from T. pallidum and T. pertenue are different. The clinical symptoms in syphilis and yaws are very different, but sequence analysis of TpE has shown that the TpE proteins are indeed very similar in the two strains. This observation makes it unlikely that heterogeneity of TpE can account for the different clinical symptoms of syphilis and yaws. Sequence data for another newly sequenced surface-associated antigen of T. pallidum (molecular weight 41 kDa) indicate that this protein is involved in glucose transport and chemotaxis/motility. Intracellular factors like the molecular chaperonin GroEL have been documented both in treponemes and borreliae. This stress protein is involved in cellular repair processes and folding/assembly of protein subunits. Indirect evidence suggests that GroEL affects the ability of spirochetes to survive in the stressful environment of the infected host. Several lines of evidence suggest that the Osp proteins of Borrelia are important for host/parasite interaction. Further support for this idea has come from studies of a series of monoclonal antibodies against OspA. A monoclonal antibody against OspA (9B3D) is able to block attachment of B. burgdorferi to a cell monolayer. Borrelia loses infectivity after several passages in vitro. The loss of pathogenicity is associated with loss of specific plasmids and proteins. One of the low-passage-associated proteins (Lap30) has been cloned and sequenced. Lap30 is a lipoprotein encoded by a 38-kb plasmid, not present in high passage B. burgdorferi. Aberrant immunological processes induced by the lipopolysaccharide component of Treponema hyodysenteriae could explain the dramatic intestinal lesions in swine dysenteriae. But analysis by TLC reveals that the LPS of this treponeme is different from classical Salmonella LPS.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Outer Membrane Proteins↗

[Minocycline].

Minocycline belongs to the second generation class of cyclines. It was synthesized in 1967 and marketed in 1972. Minocycline has an antiinfectious activity with a spectrum similar to that of other cyclines, notably against Chlamydias, Treonema and Proprionibacterium acenes. The antiinflammatory activity is associated with this antiinfectious action is greater than that of first generation cyclines with specifically a modulator effect on epidermal cytokines. The pharmokinetics of minocycline is characterized by an excellent absorption, a long half-life and an important lipophilic property inducing good tissue distribution. Clinical trials of minocycline have mainly been performed in sexually transmissible diseases and in acne, a field where randomized studies are the most frequent. These trials show that the effect of minocycline is not stronger than first generation cyclines or doxycycline, but that the action is quicker than that of tetracycline at the dose of 500 mg a day. Minocycline is also efficient in nocardiasis, mycobacteriosis, leprosy, Lyme disease, pyoderma gangrenosum, autoimmune bullous dermatitis, Carteaud disease, and prurigo. However, the effect of minocycline in these different conditions has always been evaluated in open trials with a small number of patients. The usual side effects of cyclines, i.e. digestive problems, fungal infections, are less frequent than with first generation cyclines. No photosensitivity has been demonstrated although pigmentations have been described. Dizziness is a specific side effect of minocycline. Furthermore, rare but severe side effects have been reported, including hypersensitivity syndrome, autoimmune hepatitis, and lupus. Regular indications for minocycline in dermatology are acne and three sexually transmissible diseases (mycoplasm, chlamydia, treponema). Proposed dosage is 100 mg per day in sexually transmissible disease with a reduction to 50 mg per day after 15 days in acne.

Acne Vulgaris↗

[Risk of transmission of infectious diseases by transfusion].

In obstetric patients transfusion is a common procedure, it has many advantages but it also has severe risks. Since the observation that human immunodeficiency virus (HIV) infection is transmitted by transfusion, the number of preventive measures to reduce the infectious diseases transmission by this procedure has increased. The microorganisms that can be transmitted through transfusion include: human T lymphotropic virus (HTLV) I and II, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis G virus, HIV, cytomegalovirus, Treponema pallidum, Barucella sp, Toxoplasma gondii, Plasmodium sp, and Trypanosoma cruzi. The most important measure for reduce transfusion risks is the appropriate and careful use of this procedure. This article review transfusion's indication, describe the infectious diseases commonest transmitted by transfusion and analyze the preventive measures to put in practice.

Bacterial Infections↗