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Neurosyphilis.

Treponema pallidum, the bacterium that causes syphilis, invades the central nervous system early in the course of disease but causes persistent infection in only a subset of infected persons. Individuals with persistent infection or asymptomatic meningitis are at risk for developing symptomatic neurosyphilis if they are not treated with a drug regimen that achieves sufficient drug levels in cerebrospinal fluid to kill the organism. In this article, recent studies that address the risk, diagnosis, and management of neurosyphilis are discussed within the context of a brief review. Particular attention is given to current controversies. In the developed world, these issues are particularly relevant to persons who are infected with HIV.

Animals↗

Herpes simplex virus type 2 seropositivity among urban adults in Africa: results from two cross-sectional surveys in Addis Ababa, Ethiopia.

BACKGROUND: Although several surveys investigating the epidemiology of herpes simplex virus type 2 (HSV-2) infection using type-specific immunologic assays have been carried out in Africa, none has examined the risk factors for HSV-2 infection in a representative sample from an urban adult population. GOALS: To estimate the prevalence of HSV-2 infection in the adult population of Addis Ababa, Ethiopia, and to identify risk factors for HSV-2 infection. STUDY DESIGN: Two cross-sectional surveys, one community-based (June to September 1996, n = 506) and one factory-based (February to November 1997, n = 657), were conducted. Samples were tested for HSV-2 immunoglobulin G antibodies using type-specific enzyme-linked immunoassays (ELISA). RESULTS: In the community-based survey, HSV-2 prevalence increased with age until 25 years, then leveled off at 50% in both genders. The same independent predictors of HSV-2 infection were identified in both genders: older age, higher lifetime number of sexual partners, positive HIV serology, and positive Treponema pallidum hemagglutination serology. CONCLUSIONS: This study confirmed the high prevalence of HSV-2 infection among adults in an African urban population and its association with HIV infection. Prevention of HSV-2 and other sexually transmitted infections through partner reduction and condom use should be encouraged.

Adolescent↗

The flanking region sequences of the 15-kDa lipoprotein gene differentiate pathogenic treponemes.

The species Treponema pallidum includes three subspecies (pallidum, pertenue, and endemicum) that cause syphilis, yaws, and bejel, respectively. A closely related species, Treponema paraluiscuniculi, is the etiologic agent of venereal syphilis in rabbits but does not infect humans. Although these treponemes cause distinct diseases, no laboratory method for differentiation has been reported. Genetic signatures were defined in the 5' and 3' flanking regions of the 15-kDa lipoprotein gene (tpp15) that distinguish the human pathogens and T. paraluiscuniculi, as well as distinguishing T. pallidum subsp. pallidum from the causes of human nonvenereal treponematoses. A single Eco47III restriction site in the 5' flanking region differentiates T. pallidum subsp. pallidum from the other subspecies and species, and an XcmI site in the 3' flanking region differentiates T. paraluiscuniculi from the human pathogens. Polymerase chain reaction methods and restriction polymorphism were used to analyze 27 strains of pathogenic Treponema species.

Animals↗

Roxithromycin (RU 965): effective therapy for experimental syphilis infection in rabbits.

Roxithromycin (RU 965), a new macrolide antibiotic, was shown to be effective for therapy of active syphilis in rabbits. Dark-field-positive lesions were produced in adult male rabbits by intradermal inoculation of approximately 10(6) Treponema pallidum organisms at each of 11 sites. Beginning 7 days after infection, six animals per group were treated with benzathine penicillin G (200,000 U, intramuscularly, weekly for 2 weeks) or roxithromycin (15 mg/kg of body weight, orally, twice daily for 15 days); six animals were not treated. Chancres in untreated animals were dark-field positive throughout the 16-day observation period; all benzathine penicillin-treated rabbits were dark-field negative 1 day after the initiation of therapy. Five of six animals treated with roxithromycin were dark-field negative on day 3 following the initiation of therapy; the sixth animal was dark-field negative by day 6. Lesions in untreated animals reached a mean (+/- standard deviation) maximum diameter of 14.7 +/- 1.91 mm compared with 8.4 +/- 3.6 mm for benzathine penicillin-treated (P less than 0.005) and 10.4 +/- 1.2 mm for roxithromycin-treated (P less than 0.001) animals. Ulceration occurred at 62 of 66 lesions in untreated animals compared with 0 of 66 lesions in each treated group. At 3, 6, and 12 weeks postinfection, Venereal Disease Research Laboratory antibody titers were significantly higher (P less than 0.05) in untreated than in treated animals. Titers in penicillin-treated versus roxithromycin-treated animals were significantly different at 6 weeks postinfection but not at 3 and 12 weeks postinfection. Transfer of tissue from treated rabbits to seronegative recipient animals did not reveal any evidence of persistent infection in the benzathine penicillin- or roxithromycin-treated animals. These findings indicate that benzathine penicillin and roxithromycin, at the doses indicated above, are effective in treating active syphilis in rabbit model.

Animals↗

Clinical findings in female genital schistosomiasis in Madagascar.

To assess the morbidity of S. haematobium infection in women of reproductive age (15-49 years) in the western part of Madagascar, the village of Betalatala with a prevalence of urinary schistosomiasis in women of 75.6% (95% confidence limit 69.3 to 81.9%) was compared with a neighbouring village with similar socio-economic characteristics and a prevalence of 5.0% (95% confidence limit 0 to 11.75%). The women were questioned in Malagasy about obstetrical history and urogynecological symptoms. They were examined gynaecologically, parasitologically and by ultrasonography. Important STDs were excluded by appropriate diagnostics. In Betalatala significantly more women reported a history of spontaneous abortion (P < 0.01), complaints of irregular menstruation (P < 0.001), pelvic pain (<0.05), vaginal discharge (P < 0.0001), dysuria (P < 0.05) and haematuria (P < 0.01) than in the control village. Biopsies were obtained from the cervix of 36 women with macroscopical lesions, and in 12 cases S. haematobium eggs were found by histological sectioning (33.3%). In the control village no eggs were detected in the histological sections of biopsies taken from 14 women. (P < 0.05). Infections with Candida albicans, Trichomonas vaginalis, Gardnerella vaginalis and Treponema pallidum were found in similar frequencies in both villages. In 9.8% of the women in Betalatala abnormalities of the upper reproductive tract were revealed by ultrasonography versus none in the women from the control village (P < 0.05). Echographic abnormalities of the urinary tract were present in 24% and 3% of the women in the study village and in the control village, respectively (P < 0.0001). These findings were accompanied by an elevated frequency of haematuria (55% versus 20%) and proteinuria (70.4% versus 25%) in the study population (P < 0.0001). Our study indicates that S. haematobium infection in women may not only cause symptoms in the urinary tract, but also frequently in the lower and upper reproductive tract.

Abortion, Spontaneous↗

[Syphilis. Current physiobiological data. I. The bacteriological problem].

For lack of being able to grow Treponema pallidum, the only method which allows us to study the biology of this germ and the physiopathology of this infection lies in researches in experimental syphilis. After pointing out the different aspects of Treponema pallidum, either with light microscopy or electron microscopy, the authors review the different kinds of reproduction suggested by syphiligraphs, the recent trials to cultivate the treponema, and the processes of elimination. Then, they examine the biological properties and the antigenic structure of T.p. as it has been established by comparison with cultivable spirochetes. To end with, the authors show that both the TPI test and the FTA test are two very specific reactions; these tests mean nothing but the fact that the patient has been in contact with the antigens of Treponema pallidum and the quantitative tests cannot be considered as expressing the infectious potential capacity.

Animals↗

Fetal syphilis: clinical and laboratory characteristics.

OBJECTIVE: To examine the pathophysiology of fetal syphilis and correlate hematologic, immunologic, and sonographic findings. METHODS: Twenty-four women with untreated syphilis during pregnancy were prospectively identified. Sonography with amniocentesis and percutaneous umbilical blood sampling were performed. Darkfield examination, rabbit infectivity testing, and polymerase chain reaction for detection of Treponema pallidum were performed on amniotic fluid. Hematologic and chemical testing of fetal blood was performed using standard techniques. Fetal antitreponemal IgM was detected by Western blot assay. Maternal syphilis was treated with 2.4 to 4.8 million units of benzathine penicillin G intramuscularly. Neonatal outcomes and signs of congenital syphilis were recorded. RESULTS: Six women had primary, 12 had secondary, and six had early latent syphilis. Sixty-six percent of fetuses (95% confidence interval [CI] 47%, 82%) had either congenital syphilis or detection of Treponema pallidum in amniotic fluid. Sixty-six percent had hepatomegaly, including three fetuses (12.5%, 95% CI 4%, 31%) with ascites. Fetal antitreponemal IgM was detected in three cases. Abnormal liver transaminases were found in 88% (CI 69%, 96%), anemia in 26% (CI 13%, 47%), and thrombocytopenia in 35% (CI 19%, 55%). Maternal treatment was successful in 83% (CI 64%, 93%). Risk of treatment failure was significantly increased when hepatomegaly and ascites were present (P =.01). CONCLUSION: Findings with fetal syphilis are similar to those of neonatal syphilis. We hypothesize that fetal transaminase elevation occurs early in the course of infection; hematologic abnormalities and hydrops occur later. Severity of disease may be associated with risk of treatment failure.

Adult↗

Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta-analysis.

OBJECTIVES: Male circumcision is associated with reduced risk of HIV infection. This may be partly because of a protective effect of circumcision on other sexually transmitted infections (STI), especially those causing genital ulcers, but evidence for such protection is unclear. Our objective was to conduct a systematic review and meta-analyses of the associations between male circumcision and infection with herpes simplex virus type 2 (HSV-2), Treponema pallidum, or Haemophilus ducreyi. METHODS: Electronic databases (1950-2004) were searched using keywords and text terms for herpes simplex, syphilis, chancroid, ulcerative sexually transmitted diseases, or their causative agents, in conjunction with terms to identify epidemiological studies. References of key articles were hand searched, and data were extracted using standardised forms. Random effects models were used to summarise relative risk (RR) where appropriate. RESULTS: 26 articles met the inclusion criteria. Most syphilis studies reported a substantially reduced risk among circumcised men (summary RR = 0.67, 95% confidence interval (CI) 0.54 to 0.83), although there was significant between study heterogeneity (p = 0.01). The reduced risk of HSV-2 infection was of borderline statistical significance (summary RR = 0.88, 95% CI 0.77 to 1.01). Circumcised men were at lower risk of chancroid in six of seven studies (individual study RRs: 0.12 to 1.11). CONCLUSIONS: This first systematic review of male circumcision and ulcerative STI strongly indicates that circumcised men are at lower risk of chancroid and syphilis. There is less association with HSV-2. Potential male circumcision interventions to reduce HIV in high risk populations may provide additional benefit by protecting against other STI.

Chancroid↗

A histopathologic and immunologic study of the course of syphilis in the experimentally infected rabbit. Demonstration of long-lasting cellular immunity.

Inoculation of the causative agent of syphilis, Treponema pallidum into the testes of rabbits initiated the following sequence of events: 1) a rapid proliferation of organisms in the interstitial tissues of the testes, reaching a maximum at about 10-11 days after infection; 2) systemic spread of organisms primarily in the lymphoid organs; 3) a prompt immune response manifested by hyperplasia of T cell domains in draining lymph nodes and spleen, blast transformation responses of lymphoid cells to sonicates of T pallidum, the appearance of serum antibody, and the marked infiltration of the infected areas of the testes by T cells; 4) essential clearing of organisms identified by immunofluorescence from the infected site 10-14 days after infection associated with evolution of the inflammatory response from primarily a T cell infiltrate to a larger mononuclear cell type, and the immunofluorescent identification of presumptive T pallidum antigen in macrophages; 5) interstitial fibrosis or resolution 17-21 days after infection so that examination of infected testes from 1 to 24 months later reveals foci of tubular atrophy and fibrosis of varying size, alternating with regenerated tubules, separated by interstitial areas with only minimal fibrosis. During the long period of latency there is no evidence of atrophy or hypoplasia of the lymphoid organs and long-lasting T cell memory with regard to T pallidum sonicates is demonstrable. Reinfection of previously inoculated rabbits indicates partial protection at 25 days after infection followed by essentially complete protection after 55 days. It is concluded that there is a prompt and long-lasting immune response to T pallidum in experimentally infected rabbits. The main mechanism for destruction of infecting organisms appears to be T-cell-initiated macrophage-mediated destruction, but a role for antibody dependent phagocytosis cannot be ruled out. The reason that some organisms may survive in various body organs remains unknown, but possible explanations are presented.

Animals↗

Treponemal infection specifically enhances node T-cell regulation of macrophage activity.

Hamsters experimentally inoculated in the inguinal region with Treponema pallidum subsp. endemicum develop considerable pathology at that site. We examined the cell populations from these inguinal lymph nodes to determine their intercellular responses to infection. In vitro, syphilitic-node T cells markedly suppressed C3b receptor-mediated ingestion (C3bMI) in syphilitic macrophages derived from sites both proximal and distal to the inoculation. This activity was more pronounced when node T cells rather than peritoneal T cells were used. When treponemal preparations or live treponemes were added to the coculture system, the suppression was specifically enhanced, whereas the addition of heterologous agents did not promote this effect. Syphilitic macrophages from either compartment cultured alone showed no significant inhibition of C3bMI. In parallel studies on syphilitic macrophages, we observed that the expression of Ia quickly became elevated and was sustained throughout the infection. Moreover, in vitro culturing of the syphilitic-node T cells with these macrophages did not alter this function. These observations suggest that the syphilitic node contains a subpopulation of T cells that can selectively suppress macrophage C3bMI activity and concurrently regulate their cellular response to treponemal infection.

Animals↗

Rat model of polymicrobial infection, immunity, and alveolar bone resorption in periodontal disease.

One of the predominant polymicrobial infections of humans is expressed clinically as periodontal disease. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia have been strongly implicated as members of a pathogenic consortium in the etiology of adult periodontitis. In this study we hypothesized that P. gingivalis, T. denticola, and T. forsythia are synergistic in terms of virulence potential and induce chronic periodontal inflammation that leads to alveolar bone resorption in a polymicrobial infection in rats. Groups of rats were infected with either P. gingivalis, T. denticola, or T. forsythia in monomicrobial infections or with all three species in polymicrobial oral infections with or without Fusobacterium nucleatum. PCR analyses of oral microbial samples demonstrated that rats infected with one bacterium were orally colonized by each of the bacteria during the study interval, and increased serum immunoglobulin G (IgG) antibody levels substantiated the interaction of the host with the infecting bacteria. PCR analyses of the rats with polymicrobial infections demonstrated that most rats were infected with P. gingivalis, T. denticola, and T. forsythia as a consortium. Furthermore, all rats exhibited a significant increase in the level of IgG antibody to the polymicrobial consortium. Radiographic measurement of alveolar bone resorption showed that rats infected with the polymicrobial consortium with or without F. nucleatum exhibited significantly increased alveolar bone resorption compared to the resorption in uninfected control rats, as well as the resorption in rats infected with one of the microbes. These results documented that P. gingivalis, T. denticola, and T. forsythia not only exist as a consortium that is associated with chronic periodontitis but also exhibit synergistic virulence resulting in the immunoinflammatory bone resorption characteristic of periodontitis.

Alveolar Bone Loss↗

Treponema pallidum-immobilizing antibodies in guinea pig experimental syphilis.

Treponema pallidum-immobilizing (TPI) antibodies were examined in intradermally infected inbred strain 13 and adoptively immune inbred strain 2 guinea pigs. Both strains of animals produced TPI antibodies at or after 90 days of infection. TPI antibodies were not associated with the protective mechanism(s) operative after challenge in adoptively immune animals.

Animals↗

Swine dysentery: pathogenicity of Treponema hyodysenteriae.

When pure cultures of Treponema hyodysenteriae were orally inoculated into pigs, severe disease characteristic of swine dysentery developed. Less severe lesions were produced by oral inoculation of infective minced colon. Noninoculated pigs were used as controls. Inoculations of surgically isolated porcine colonic loops with either pure cultures or infective minced colon produced lesions only in the injected loop; the adjacent noninjected colon remained normal. Pigs and other experimental animals, including rabbits, guinea pigs, and mice, inoculated with washed cultures by various parenteral routes remained normal.

Administration, Oral↗

Sexually transmitted infections and risk factors among truck stand workers in Dhaka, Bangladesh.

OBJECTIVE: This study was conducted to determine the prevalence of selected sexually transmitted infections (STIs) and their risk factors among workers in and near a truck stand in Dhaka, Bangladesh. STUDY DESIGN: A random sample of 696 men and 206 women were recruited into a cross-sectional study using a census that enumerated transport agents, motor mechanics, laborers, and vendors in Tejgaon truck stand. RESULTS: The prevalence rates of syphilis (rapid plasma reagin and Treponema pallidum hemagglutination), gonorrhea (polymerase chain reaction [PCR]), and chlamydial infections (PCR) among men were 4.1%, 7.7%, and 2.3%, respectively, and among women were 2.9%, 8.3%, and 5.2%. Multivariable analysis revealed that having >or=2 sex partners in the last month, never using a condom with sex workers, and ever injecting narcotics were significant predictors of STI among men. Being never married, working as a laborer, older age, and living within the truck stand were significant predictors of practicing high-risk behaviors among men, but none predicted infection with STIs. CONCLUSIONS: Both behavioral and STI data suggest that truck stand workers should be included in the STI/HIV intervention programs.

Adolescent↗

Family planning services in developing countries: an opportunity to treat asymptomatic and unrecognised genital tract infections?

OBJECTIVE: To determine the prevalence of asymptomatic and unrecognised genital tract infections among women attending a family planning clinic in rural South Africa. METHODS: 189 consecutive women had genital samples taken to diagnose infection with Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Candida albicans, Treponema pallidum, and HIV, and to diagnose bacterial vaginosis. RESULTS: Mean age was 25 years; 155 (82%) were unmarried, 156 (83%) were currently using contraception, and 41 (22%) reported having an STD treated in the preceding 12 months. Although none volunteered abnormal urogenital symptoms, 74 (39%) had at least one elicited by direct questioning. 119 women (63%) had at least one genital infection: N gonorrhoeae (eight; 4%), C trachomatis (14; 8%), T vaginalis (26; 14%), C albicans (56; 30%), active syphilis (15; 8%), HIV (44; 24%), and bacterial vaginosis (29; 15%). 49 women (26%) had multiple infections. Most infections (71; 60%) were asymptomatic. Symptomatic women failed to recognise and report their symptoms, and routine services failed to detect the infections. CONCLUSION: Prevalence of genital tract infection is high among these women, most infections are asymptomatic, and symptomatic infections are frequently not recognised. Women attending family planning clinics in such settings should be screened for syphilis and offered testing for HIV infection. Strategies to detect and treat other genital infections need to be developed.

Adult↗

[Pasteurella anatipestifer: a controllable farm problem].

The performance of 13 flocks of ducks on a duck farm decreased markedly. Post-mortem and bacteriological examinations indicated that Pasteurella anatipestifer was a major cause, although Salmonella spp., Escherichia coli and Treponema spp. were also detected. Use of an autovaccine against Pasteurella anatipestifer markedly reduced the signs and symptoms in the second part of fattening period.

Animals↗