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PubMed1982

Studies on the pathogenesis of the Jarisch-Herxheimer reaction: development of an animal model and evidence against a role for classical endotoxin.

The etiology of the Jarisch-Herxheimer reaction is unknown, but the reaction may result from toxic products of dead or dying treponemes reacting with sensitized syphilitic tissues. Because of similarities of spirochetes with gram-negative bacteria, endotoxin has been proposed as the responsible toxin. In 19 patients with syphilis, a reaction occurred in 15 (79%) during treatment with penicillin. Endotoxemia was not found by the limulus amoebocyte lysate test. All animal model of the Jarisch-Herxheimer reaction was developed in rabbits infected with Treponema pallidum. When treated with penicillin, 18 (78%) of 23 rabbits infected 18-29 days previously developed a reaction that resembled that in humans. Endotoxemia was not detected by the lysate test. After the reaction, rabbits were not refractory to the pyrogenic effects of endotoxin, and syphilitic rabbits rendered tolerant to endotoxin still developed fever when treated with penicillin. These data suggest that classical endotoxin is not the cause of the Jarisch-Herxheimer reaction.

Adult↗
PubMed1991

Circulating immune complexes in experimental syphilis and their relation to immunological response against Treponema pallidum.

It was found that circulating immune complexes (CIC) were formed in rabbits at different times after infection with Treponema pallidum. The CIC which appeared at the beginning of the disease were short-lived (2-6 weeks) but those appearing later than 20 weeks after infection remained for 10-25 weeks. CIC contained both IgM and IgG classes of immunoglobulin. The antibodies present in CIC were found to be specific and nonspecific for T. pallidum. The presence of CIC led to a marked decline of treponemal antibodies in rabbit sera. The cell-mediated immune response measured by the macrophage migration inhibition (MMI) test at the beginning of the disease (up to 12 weeks) was not decreased. However, when syphilis lasted for more than 14 weeks and when CIC were formed mainly from IgG, a distinct decrease in the ability of lymphocytes to cause MMI was observed. These findings strongly suggest that IgG-complexes suppress the immunological responsiveness of lymphocytes against T. pallidum which in turn facilitates the multiplication of treponemes in the host.

Animals↗
PubMed1976

Passive hemolysis test for antibody to Treponema hyodysenteriae.

Swine were infected orally with pure cultures of Treponema hyodysenteriae, and the humoral antibody response was measured by a passive hemolysis test (passive hemagglutination test with the use of complement). Antibody to T. hyodysenteriae was detected as early as 1 week and later on at 4 months after exposure. However, peak serum titers were obtained after challenge at 4 weeks postinfection. The usefulness of the test as a potential diagnostic tool for antibody to T. hyodysenteriae is discussed.

Animals↗
PubMed1998

Syphilis.

Syphilis was first recognized as a distinct syndrome in Europe in the fifteenth century. Despite knowledge of congenital infection for more than 450 years and the existence of adequate therapy for 55 years, congenital infection remains a problem for the practicing clinician. Syphilis is caused by Treponema pallidum. Infection may be transmitted horizontally by sexual contact and vertically as a result of hematogenous dissemination across the placenta. Syphilis is classified as primary, secondary, latent, and tertiary. The diagnosis may be established by darkfield examination of clinical lesions and by serological assays. The drug of choice for syphilis is penicillin. This agent is the only antibiotic of proven value for the treatment of congenital syphilis. Accordingly, infected pregnant women who are allergic to beta-lactam antibiotics must be desensitized and then treated with penicillin.

Congenital Abnormalities↗
PubMed1986

Eliminating organisms against Treponema hyodysenteriae in the gut of mice.

Ta:CF#1 mice lost their high susceptibility to Treponema hyodysenteriae infection after being mingled with Slc:ICR mice which had no susceptibility to the infection. Ta:CF#1 mice also lost susceptibility to the infection after being treated orally with fecal suspensions from Slc:ICR mice; treatment with heated (70 degrees C, 15 min) or filtered (pore size 0.2 micron) fecal suspensions did not cause a loss of susceptibility. Furthermore, even after the infection had established, Ta:CF#1 mice became free from T. hyodysenteriae and cecal lesions by oral treatment with the fecal suspensions. When Slc:ICR mice were treated with spectinomycin throughout the experiment, they became susceptible to the infection. These studies indicate that there exist eliminating organisms against T. hyodysenteriae in the gut of mice.

Animals↗
PubMed1986

Investigations into the location of Treponema hyodysenteriae in the cecum of experimentally infected young broiler chicks by light- and electronmicroscopy.

Numerous Treponema hyodysenteriae were present both on the mucosal surface and in the deep crypts of the cecum of young broiler chicks 7 and 14 days after inoculation with the treponemes. The treponemes in the ceca of chicks inoculated with 10(8) cells were observed more frequently than those of chicks inoculated with 10(7) cells. The treponemes in the ceca were observed by light microscopy, scanning electron microscopy and transmission electron microscopy. The lesions were primarily confined to the cecum. Desquamation of epithelial cells, edema, leukocytic infiltration and hemorrhage were observed in the mucosae.

Animals↗
PubMed2003

Genetic relatedness and phenotypic characteristics of Treponema associated with human periodontal tissues and ruminant foot disease.

Treponema have been implicated recently in the pathogenesis of digital dermatitis (DD) and contagious ovine digital dermatitis (CODD) that are infectious diseases of bovine and ovine foot tissues, respectively. Previous analyses of treponemal 16S rDNA sequences, PCR-amplified directly from DD or CODD lesions, have suggested relatedness of animal Treponema to some human oral Treponema species isolated from periodontal tissues. In this study a range of adhesion and virulence-related properties of three animal Treponema isolates have been compared with representative human oral strains of Treponema denticola and Treponema vincentii. In adhesion assays using biotinylated treponemal cells, T. denticola cells bound in consistently higher numbers to fibronectin, laminin, collagen type I, gelatin, keratin and lactoferrin than did T. vincentii or animal Treponema isolates. However, animal DD strains adhered to fibrinogen at equivalent or greater levels than T. denticola. All Treponema strains bound to the amino-terminal heparin I/fibrin I domain of fibronectin. 16S rDNA sequence analyses placed ovine strain UB1090 and bovine strain UB1467 within a cluster that was phylogenetically related to T. vincentii, while ovine strain UB1466 appeared more closely related to T. denticola. These observations correlated with phenotypic properties. Thus, T. denticola ATCC 35405, GM-1, and Treponema UB1466 had similar outer-membrane protein profiles, produced chymotrypsin-like protease (CTLP), trypsin-like protease and high levels of proline iminopeptidase, and co-aggregated with human oral bacteria Porphyromonas gingivalis and Streptococcus crista. Conversely, T. vincentii ATCC 35580, D2A-2, and animal strains UB1090 and UB1467 did not express CTLP or trypsin-like protease and did not co-aggregate with P. gingivalis or S. crista. Taken collectively, these results suggest that human oral-related Treponema have broad host specificity and that similar control or preventive strategies might be developed for human and animal Treponema-associated infections.

Animals↗
PubMed2000

Human immunodeficiency virus infection and genital ulcer disease in South Africa: the herpetic connection.

BACKGROUND AND OBJECTIVES: While genital ulcers are a risk factor in HIV infection, the association of specific agents of genital ulcer disease (GUD) with HIV infection may vary. GOAL: To determine the etiology of GUD in HIV-infected and HIV-uninfected men attending sexually transmitted disease (STD) clinics in Durban, Johannesburg, and Cape Town, South Africa, and the association of previous and current sexually transmitted infections with HIV infection in men with ulcerative and nonulcerative STDs. STUDY DESIGN: A cross-sectional study of 558 men with genital ulcers and 602 men with urethritis. RESULTS: Patients with GUD were more likely to be infected with HIV than patients with urethritis (39.4% versus 21.4%, P< or =0.001). Herpes simplex virus 2 (HSV-2) was the most common agent identified in ulcer specimens (35.9%), and was detected in a significantly higher proportion of ulcer specimens from HIV-infected patients than in specimens from HIV-uninfected patients (47.4% versus 28.2%, P< or =0.001). Patients infected with HIV-1 were significantly more likely to have HSV-2 infection, as measured by the presence of the antibody to glycoprotein G-2, than patients not infected with HIV (63.1% versus 38.5%, P< or =0.001). Patients infected with HIV-1 were also significantly more likely to have initial HSV-2 infection than HIV-uninfected patients with GUD (50.0% versus 31.6%, P = 0.007). Haemophilus ducreyi was detected in 31.7% of ulcer specimens; prevalence did not vary by HIV-infection status. Treponema pallidum DNA was detected significantly less frequently in ulcer specimens from patients infected with HIV than in specimens from patients not infected with HIV (10.2% versus 26%, P< or =0.001); no association was found between HIV-infection status and fluorescent treponemal antibody absorption test seroreactivity, even when men with M-PCR-positive syphilis lesions were excluded from the analyses. CONCLUSION: The authors found that HSV-2 is a more common etiology of GUD than has been suggested by previous studies conducted in South Africa; serologic evidence of HSV-2 infection and current cases of genital herpes are strongly associated with HIV infection among men who present to STD clinics with GUD or urethritis.

Adolescent↗
PubMed2005

Use of the serologic testing algorithm for recent HIV seroconversion (STARHS) to identify recently acquired HIV infections in men with early syphilis in Los Angeles County.

BACKGROUND: Syphilis outbreaks among men who have sex with men (MSM) in the United States, many of whom are HIV infected, have prompted increased concern for HIV transmission. METHODS: To identify whether men are acquiring HIV concomitantly or within the critical period of syphilis infection, banked Treponema pallidum particle agglutination-positive serum specimens from men with early syphilis infection were screened for HIV-1 antibody. Samples that were positive for HIV antibody were then tested with a less sensitive (LS) HIV-1 antibody enzyme immunoassay (serologic testing algorithm for recent HIV seroconversion [STARHS]) to identify HIV infections that occurred on average within the previous 6 months. RESULTS: Of the 212 specimens banked from men with early syphilis, 74 (35%) were HIV-positive. Of these, 15 tested non-reactive by the LS assay. Twelve of these 15 were considered to be recent infections by the LS assay and testing history. Eleven (92%) of the recent infections were among MSM. One man had primary syphilis, 6 (50%) had secondary syphilis, and 5 (42%) had early latent syphilis. Eight men (67%) reported sex with anonymous partners, and 3 (25%) reported consistent condom use. The estimated HIV incidence was 17% per year (95% confidence interval [CI]: 12%-22%) among all men with early syphilis, and it was 26% per year (95% CI: 91%-33%) among MSM. CONCLUSIONS: Syphilis epidemics in MSM may be contributing to HIV incidence in this population. The STARHS can be applied as a surveillance tool to assess HIV incidence in various at-risk populations, but further studies are necessary for validation.

Adult↗
PubMedDate not supplied

The syphilis epidemic in Connecticut: relationship to drug use and prostitution.

Syphilis rates in Connecticut increased four-fold between 1986 and 1988. During this time there were also signs of a large increase in cocaine use in the state. We studied links between these parallel trends in drug use and syphilis by examining two sources of data: information collected during syphilis case interviews and information from the syphilis screening program at the state's prison for women. As syphilis rates rose, there were large increases in the percentage of women with syphilis who reported prostitution or illicit drug use. In 1988, 41% of women with syphilis reported cocaine use, and 19% reported prostitution; 21% of male heterosexuals with syphilis reported cocaine use, and 31% reported sexual contact with prostitutes. Among incarcerated women, syphilis infection was frequent: of 113 women incarcerated for possession of illicit drugs in 1987-88, 7% were found to be infected with Treponema pallidum, and of 187 women incarcerated for prostitution in these years, 14% were infected. In both groups of incarcerated women studied, cocaine users had the highest syphilis rates, and those who administered drugs nonintravenously had rates similar to those who administered drugs intravenously. We concluded that the syphilis epidemic in Connecticut is related to the increase in use of illicit drugs (primarily cocaine) and that female drug users are at very high risk of syphilis regardless of whether they administer drugs intravenously or nonintravenously. We recommend that syphilis control efforts focus on wider serologic screening and early treatment of drug users, prostitutes, and their sex partners.

Connecticut↗
PubMed2002

Preparation of amniotic membrane for ocular surface reconstruction.

We describe the preparation and preservation of human amniotic membrane required for transplantation in the management of ocular surface diseases. Informed consent is obtained and the donor is screened to exclude risk of transmissible infections such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and Treponema pallidum infections. Ideally, the media and washing solutions needed for the preparation of amniotic membrane are prepared only a week to 10 days prior to use and not stored in the freezer weeks ahead. The AM obtained under sterile conditions after elective caesarian section is washed free of blood clots and chorion. With the epithelial surface up, amniotic membrane is spread uniformly without folds or tears on individually sterilized 0.22 micron nitrocellulose membranes of the required sizes. The prepared filter membrane with the adherent amniotic membrane is placed in the preservative medium and stored at -80 degrees C. The membranes are released when the repeat serology for HIV after the window period has excluded virus infection in the donor. Depending on consumption they may be used up to 6 months after preparation, though many have recommended storage for an indefinite period. Since the amniotic membrane has only incomplete expression of HLA antigens and amniotic epithelial cells do not express them, it is not rejected after transplantation. The presence of several cytokines in the amniotic membrane promotes epithelialization with reduction of fibrosis during healing.

Amnion↗
PubMed1993

Characterization of the serum requirement for macrophage-mediated killing of Treponema pallidum ssp. pallidum: relationship to the development of opsonizing antibodies.

Serum pools were collected from rabbits bled at various times after intra-testicular infection with Treponema pallidum ssp. pallidum. These were tested for their ability to opsonize T. pallidum and promote killing of the organisms by macrophages. Compared to normal sera, significant opsonization was first seen on day 10 of infection as measured by both ingestion (P < 0.001) and macrophage-mediated killing (P = 0.006); significant levels of functional antibodies persisted through 300 days of infection. Although opsonic activity peaked early in infection, antibodies that promoted optimal macrophage-mediated killing developed much later, suggesting that these two functions may represent activities of antibodies with differing specificities or affinities. The initial development of antibodies that augment both phagocytosis and killing corresponds with the in vivo clearance of treponemes from the primary site of infection. These observations support the hypothesis that macrophages are the major effector mechanism for elimination of T. pallidum during early syphilis infection.

Animals↗
PubMed1984

Response of syphilitic rabbits to reinfection with homologous and heterologous Treponema pallidum strains.

Rabbits infected intradermally with 10(3) Treponema pallidum (Melbourne 1) cells were examined for their susceptibility to reinfection with 10(2) T. pallidum cells (homologous or heterologous strains) at various intervals after the initial infection. At 2.5 weeks after infection, the rabbits were extremely sensitive to reinfection and developed syphilitic lesions significantly faster (i.e., shorter latent periods) than control rabbits that had not received the initial infection. This phenomenon may represent a state of immunosuppression or hypersensitivity in the infected rabbits. Whatever its etiology (at present unknown), it was a transient state since at 5 weeks after infection the rabbits were no longer different from control rabbits in their susceptibility to reinfection. They showed neither immunity (i.e., longer latent periods) nor immunosuppression or hypersensitivity (shorter latent periods) upon reinfection. At 6.5 weeks after infection, two of the three experimental rabbits were fully immune (no lesions upon reinfection), whereas the other rabbit exhibited immunosuppression or hypersensitivity upon reinfection. At 7.5 and 10 weeks after infection, all of the experimental rabbits were immune to reinfection. We conclude that syphilitic rabbits show a biphasic response to reinfection, consisting of an early phase of enhanced sensitivity to T. pallidum and a later phase of immunity to T. pallidum.

Animals↗
PubMed1988

The clinical use of macrolides.

Macrolides are active against Streptococcus pneumoniae, Legionella spp. and Mycoplasma pneumoniae, the main causes of community-acquired pneumonia They may therefore be used for the empirical treatment of community-acquired pneumonia, although emergent resistance in Str. pneumoniae limits their use in some parts of the world. In patients with bronchitis the use of macrolides reduces the severity and duration of symptoms. Macrolides have also been used successfully in the treatment of otitis media and sinusitis; combination with sulphonamides may be desirable. They may be effective in eradicating the carrier state of Str. pyogenes, Bordetella pertussis, Corynebacterium diptheriae, and Neisseria meningitidis. Macrolides provide alternative therapy for the prophylaxis of recurrent acute rheumatic fever and of infective endocarditis after dental treatment. The cure rate with macrolides of streptococcal skin infections and of minor staphylococcal infections is equal to that achieved with penicillins. In diarrhoea due to Campylobacter jejuni, the administration of macrolides shortens the duration of the faecal excretion of organisms and may give clinical improvement in severe disease. Macrolides are the drugs of choice for infections due to Chlamydia trachomatis in pregnancy and for Haemophilus ducreyi infections. They are effective alternative therapy to benzylpenicillin for the treatment of N. gonorrhoeae and Treponema pallidum infections.

Anti-Bacterial Agents↗
PubMed1984

Cobra venom factor abrogates passive humoral resistance to syphilitic infection in hamsters.

Cobra venom factor, an agent commonly used to deplete complement, lowered the resistance of hamsters to infection with Treponema pallidum subsp. endemicum , as shown by a more rapid development of cutaneous lesions in infected animals treated with cobra venom factor than in infected, untreated animals. Cobra venom factor also abrogated the passive transfer of resistance by injection of serum from syphilitic immune hamsters. These results indicate that complement influences the pathogenesis of treponemal infection.

Animals↗
PubMed1985

Lymphocyte function in experimental endemic syphilis of Syrian hamsters.

We have studied the changes in the lymph nodes, spleen and thymus that occur in inbred LSH Syrian hamsters infected with Treponema pallidum Bosnia A, the causative agent of endemic syphilis, as well as the B-cell responses of these infected animals to helper T-cell independent and dependent antigens. The lymph nodes increased significantly in weight up to 6 weeks after infection, and contained viable treponemes. No significant changes in the spleen weight were observed, and no viable treponemes could be recovered from the spleen. However, the size of the thymus decreased steadily during the course of the disease. The relative number of Ig+ cells (B cells) increased in the spleen and regional lymph nodes, whereas the relative number of T cells decreased during the course of infection. In both the spleen and lymph nodes, the relative number of macrophages increased initially and decreased thereafter in the form of a bell-shaped curve showing a peak at 4-6 weeks of infection. The ability of splenic lymphocytes from infected hamsters to mount a primary PFC response to pneumococcal polysaccharide type III (SIII), a helper T-cell independent antigen, was elevated throughout the course of infection. However, the splenic PFC response to sheep erythrocytes (SRBC), a helper T-cell dependent antigen, was increased only during the first 4 weeks of infection and progressively decreased thereafter. The PFC responses of infected lymph node lymphocytes to both SIII and SRBC were increased during the first 4 weeks and decreased thereafter. These data suggested that atrophy of the thymus seen in syphilitic infection is accompanied by the complex losses of subsets of T cells and altered B-cell functions. An early loss of suppressor T cells in both the lymph nodes and spleen occurs concomitantly with a loss of T helper cells and heterologous (treponema-unrelated) B-cell functions in the lymph nodes. Helper T cells are lost from the spleen only in the later stages of infection, whereas splenic B-cell functions remain intact throughout the course of the disease. These findings were further tested by in vitro methods where splenic and lymph node lymphocytes from infected hamsters were examined for their ability to respond to Con A in terms of the induction of antigen non-specific suppressor T cells. The mixing of Con A stimulated splenic or lymph node lymphocytes from infected hamsters was unable to inhibit the primary antibody responses of SRBC as compared to the normal control.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1981

Analysis of serum IgG against Treponema pallidum protein antigens in experimentally infected rabbits.

Sensitive and highly specific radioimmunoprecipitation and gel electrophoreses-fluorography were used to monitor the serum IgG response of experimentally infected rabbits against key protein antigens of Treponema pallidum. The sera from six rabbits challenged intradermally (ID) and six intratesticularly (IT) with T pallidum were examined over a period of four months. A specific antibody response to most treponemal surface proteins (including those ligands implicated as mediating host-cell-surface adherence) developed by about day 20 after inoculation. Maximum antibody concentrations against most of these immunogens were detected by day 50 in all animals irrespective of the route of inoculation. Differences as well as similarities in the IgG response to infection were observed among selected rabbits. Furthermore, the antibody reactivity of each animal was comparable to that of human sera from patients with secondary syphilis. Antibody directed against treponemal outer envelope proteins was detected by preferential agglutination of washed radiolabelled organisms with protein A-bearing Staphylococcus aureus in the presence of syphilitic rabbit sera.

Animals↗