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Identification of persistent infection in experimental syphilis by PCR.

The studies described herein were designed to evaluate the usefulness of the PCR in detecting persistent syphilitic infection. Three groups of animals were used: a nonimmune group infected with Treponema pallidum (NI/TP), a nonimmune group injected with heat-killed treponemes (NI/HKTP), and an immune and reinfected group (I/TP). All animals were inoculated with similar numbers of organisms distributed at 10 sites on the clipped back and in both testes. The persistence of the treponemes was examined by PCR and the rabbit infectivity test (RIT). The kinetic studies and statistical analysis of their results demonstrated that the rate of bacterial clearance from the NI/TP group was very low and incomplete at 4 months after infection. It was significantly different from those of both the NI/HKTP (P < 0.001) and I/TP (P < 0.05) groups. No statistically significant differences in treponemal elimination were found between the NI/HKTP and I/TP groups. PCR can detect the DNA of dead organisms, but the latter are eliminated by the host relatively quickly (15 to 30 days) as compared to elimination of live treponemes (>120 days). PCR results correlated well with RIT results. These data suggest that PCR-positive specimens obtained from an untreated patient(s) or collected weeks after treatment indicate persistent infection. They also show that the process of elimination of T. pallidum from primary sites of infection is prolonged and incomplete.

Animals↗

The risk of sexually transmitted diseases in human immunodeficiency virus-infected parturients.

OBJECTIVE: We assessed the prevalence of and defined the relationship between other sexually transmitted diseases and human immunodeficiency virus infection. STUDY DESIGN: We performed a case-control study among 121 human immunodeficiency virus-infected and 222 randomly selected seronegative parturient women. These women were identified from a prenatal population undergoing routine voluntary antibody screening in a large urban hospital in the southeastern United States. RESULTS: During the 24-month study period, 16,868 women consented to human immunodeficiency virus antibody screening; 121 (7.2/1000) were infected with human immunodeficiency virus. Cases were significantly more likely than controls to be infected with at least one sexually transmitted disease during pregnancy (48% vs 21%; odds ratio 3.4, 95% confidence interval 2.1 to 5.7). The prevalence of Chlamydia trachomatis and hepatitis B infection did not differ significantly among the groups. Cases were significantly more likely than controls to be infected with Treponema pallidum (29% vs 4%; odds ratio 9.6, 95% confidence interval 4.2 to 22.4). This relationship persisted after we controlled for confounding risk factors (odds ratio 9.2, 95% confidence interval 2.1 to 13.3). In addition, cases were significantly more likely than controls to be infected with Neisseria gonorrhoeae (17.2% vs 4%; odds ratio 5.2, 95% confidence interval 2.1 to 13.3). This relationship also persisted after we controlled for confounders (odds ratio 3.7, 95% confidence interval 1.4 to 10.0). CONCLUSION: Human immunodeficiency virus-infected parturient women in our center are at substantial risk of having other sexually transmitted diseases.

Adult↗

Altered immune responsiveness associated with experimental syphilis in the rabbit: elevated IgM and depressed IgG responses to sheep erythrocytes.

Generalized suppression of immunoglobulin G (IgG) synthesis detectable by depressed responses to heterologous antigens may be a mechanism by which certain parasites evade host defenses and establish chronic infections. To determine if such a mechanism occurs in syphilis, rabbits were infected with Treponema pallidum, and at weekly intervals thereafter these rabbits and uninfected controls were sensitized with SRBC. Seven days later the number of antibody-forming cells present in the spleen was determined by the Jerne plaque technique. After a transient suppression in the 1st week, IgM-PFC were elevated from up to 7 weeks after infection. The IgG response to SRBC was depressed early in infection and continued to decline to less than one-tenth of control levels over the next few weeks persisting throughout overt infection and returning to normal by the end of 2 months. IgG-PFC, and 2-ME-resistant hemagglutinins and hemolysins were also significantly depressed in infected rabbits after two immunizing doses of SRBC. These results suggest that the depressed IgG response caused by syphilitic infection may enable treponemes to evade host immunity by interfering with immunoregulatory mechanisms.

Animals↗

Azithromycin-resistant syphilis infection: San Francisco, California, 2000-2004.

BACKGROUND: The incidence of syphilis has been increasing in the United States since reaching a nadir in 2000. Several clinical trials have demonstrated that treatment with oral azithromycin may be useful for syphilis control. After reports of azithromycin treatment failures in San Francisco, we investigated the clinical and epidemiologic characteristics of patients with syphilis due to azithromycin-resistant Treponema pallidum infection. METHODS: We reviewed city-wide case reports and conducted molecular screening for patients seen at the San Francisco metropolitan STD clinic (San Francisco City Clinic) to identify patients who did not respond to azithromycin treatment for syphilis or who were infected with azithromycin-resistant T. pallidum. We conducted an epidemiologic investigation and retrospective case-control study to identify risk factors for acquiring syphilis due to azithromycin-resistant T. pallidum. RESULTS: From January 2000 through December 2004, molecular screening of 124 samples identified 46 azithromycin-resistant T. pallidum isolates and 72 wild-type T. pallidum isolates. Six instances of treatment failure were identified through record review. In total, we identified 52 case patients (one of whom had 2 episodes) and 72 control patients. All case patients were male and either gay or bisexual, and 31% (16 of 52) were infected with human immunodeficiency virus. Investigation of patient-partner links and a retrospective case-control study did not reveal a sexual network or demographic differences between cases and controls. However, 7 case patients had recently used azithromycin, compared with 1 control patient. Surveillance data demonstrated that azithromycin-resistant T. pallidum prevalence increased from 0% in 2000 to 56% in 2004 among syphilis cases observed at the San Francisco City Clinic. CONCLUSIONS: Azithromycin-resistant T. pallidum is widespread in San Francisco. We recommend against using azithromycin for the management of syphilis in communities where macrolide-resistant T. pallidum is present and recommend active surveillance for resistance in sites where azithromycin is used.

Anti-Bacterial Agents↗

Clinical expression of secondary syphilis in a patient with HIV infection.

There are increasing reports of unusual clinical features and atypical courses of syphilis in patients with acquired immunodeficiency syndrome. Recently, we had the opportunity to study an HIV-positive female patient with strong manifestations of secondary syphilis. The case is discussed together with the implications of secondary syphilis in her concomitant ocular affliction. Moreover, we comment on the clinico-therapeutic controversies brought about by the association of infection with Treponema pallidum and HIV.

Adult↗

Experimental infection of inbred guinea pigs with Treponema pallidum: development of lesions and formation of antibodies.

Inbred strain 2 and strain 13 guinea pigs were infected intradermally in the hind legs with different numbers of the virulent Nichols strain of Treponema pallidum. About 91% of the animals developed clearly visible lesions after being injected with 5 X 10(6) to 10 X 10(6) treponemes. T pallidum organisms could be isolated from skin lesions at various stages after infection. Infected animals were monitored for the production of specific treponemal and non-specific cardiolipin antibodies by the fluorescent treponemal antibody (FTA) and microhaemagglutination (MHA-TP) tests and the rapid plasma reagin (RPR) card test. Low levels of specific antibodies could be detected by both FTA and MHA-TP tests from three to four weeks after infection. Maximum titres of treponemal antibody generally occurred after week 6 and persisted for several more months. These peak titres ranged from 1/40 to 1/80 in the FTA test and 1/160 to 1/320 in the MHA-TP test. During the same period infected guinea pigs, unlike rabbits with syphilis, did not produce detectable quantities of antibodies against cardiolipin.

Animals↗

Fetal syphilis: correlation of sonographic findings and rabbit infectivity testing of amniotic fluid.

Fetal syphilis is the presumed diagnosis when the sonographic findings of fetal hydrops are found in the presence of maternal syphilis. In the absence of fetal hydrops, the diagnosis of fetal infection is difficult. We hypothesized that intra-amniotic infection would be accompanied by anatomic placental and fetal abnormalities that could be detected by ultrasonography. Rabbit infectivity testing (RIT), intratesticular inoculation of rabbits with amniotic fluid, can be used to confirm intra-amniotic infection with Treponema pallidum. Twenty-one gravidas with untreated early (primary, secondary, and early latent) syphilis underwent sonography and amniocentesis for RIT at 24 weeks of gestation or later. Antenatal sonographic findings were compared to their amniotic fluid RIT results. Hepatomegaly was significantly (P < 0.01) associated with amniotic fluid infection detected by RIT. Antenatal detection of hepatomegaly, which is probably the initial sonographic manifestation of hydrops fetalis, may ultimately identify the fetus affected with congenital syphilis.

Amniotic Fluid↗

[An etiological and clinicopathological study of early syphilis in oropharynx].

OBJECTIVE: To investigate the characteristics of the early stage treponema pallidum infected tissue in ear, nose, oropharynx and larynx and to raise relevance ratio of syphilis in nose and oropharynx and enhance doctor's self-protection awareness. METHODS: The histopathologic characteristics were studied by using HE staining, Warthin-Starry (W-S) staining was adopted to examine the treponema pallidum(TP) in lesion issue and its exudates smear for 12 cases biopsy tissues of suspicious syphilis. The diagnosis was confirmed by venereal disease research laboratory (VDRL), rapid plasma reagin circle test(RPR), treponema pallidum hemagglutination test(TPHA) and fluorescent treponemal antibody-absorption test (FTA-ABS). Treat with curing syphilis methods which published by nation. RESULTS: In the 12 cases mucous membrane specimen, the squamous epithelium proliferated, neutrophilic granulocyte infiltrated, within inherent membrane generous plasmacyte and lymphocyte infiltrated. W-S staining: plenty of treponema pallidum were found inside mucous membrane epithelium and exudate smear. Serology examination: 11 cases VDRL(++++), 7 cases RPR (+), 11 cases TPHA(+), 1 case FTA-ABS(+). After systemic treatment, 11 cases are clinically recovered. All patients serology become negative. CONCLUSION: W-S staining method can directly demonstrate histopathologic characteristics in early syphilis, in intrinsic membrane numerous plasmacyte infiltration. Combining with specific syphilis serology examination could increase diagnosis rate of syphilis in nose and oropharynx.

Adult↗

[Prevalence and risk factors associated with syphilis in women].

INTRODUCTION: Although the incidence of syphilis is generally low, it remains an important global public health problem, given its interaction with other sexually transmitted diseases (STDs). It has been shown that syphilis, due to the genital ulcers it produces, is a co-factor for acquiring other STDs, principally those of viral origin such as herpes simples type 2, hepatitis B and HIV. Many female commercial sex workers (FCSW) in Mexico have been found to have acquired good levels of knowledge about STD prevention. Nevertheless, they constitute a heterogeneous group in terms of socio-economic level, health status and type of work site; these factors in turn appear to determine their attitudes, knowledge and behavior related to acquiring and transmitting STDs, including syphilis. This study, therefore, focused on the factors associated with Treponema pallidum infection in this group of women. METHOD: Based on a sample frame of sites where female commercial sex work takes place within Mexico City, a sample of 807 FCSWs was selected; after providing informed consent, they completed a structured questionnaire. A blood sample for identifying serologic markers for STDs was collected and analyzed according to a procedure manual for STD diagnosis. Treponema pallidum was diagnosed using the RPR (Bigaux Diagnostica) screening test, and FTA-ABS (Pasteur Diagnostics) for confirmation. RESULTS: The prevalence of syphilis in this sample of FCSWs was 6.4% (52/807), and was higher among women who worked at street sites than among those who worked in massage parlors. The age of the women interviewed ranged from 17 to 58 years, with a mean of 29.2 years (SD 7.3 years); syphilis was more prevalent among women over 30 years of age. Age at first sexual intercourse ranged from 11 to 30 years, with a mean of 16 years (SD 3.1 years), which is similar to that of the general female population in Mexico. Predictive factors for T. pallidum infection, determined adjusted logistic regression, included: tupe of by work site (bar and street sites); socio-economic level (middle and low); age (over 30 years); duration of involvement in sex work (> 5 years) and number of clients per week (> 10). CONCLUSION: In spite of some limitations regarding statistical precision, this study shows that FCSWs are heterogeneous in terms of risk of acquiring STDs, including syphilis; the principal differentiating factor was shown to be the type of work site. Given that it is not belonging to a risk group but rather participating in risky practices that leads to acquiring STDs, situations that facilitate riskier or safer practices (such as type of sex work site, for sex workers) should be taken into account when studying people's risk level. STD prevention campaigns must also consider these factors, in addition to focusing on FCSWs and their clients and personal partners, so that all involved assume their responsibility for safer sex.

Adolescent↗

[Immunity in syphilis].

Following a brief review of the characteristics of the causative organism of syphilis, its maintenance in laboratory animals and its relationship to the treponemes of the tropical treponematoses, consideration is given to the immune reactions and the development of antibodies to the treponeme of syphilis. The individual tests used in the diagnosis of syphilis, especially the complement fixation reactions and the flocculation tests, as well as the reactions employing specific antigens, such as the Treponemal Immobilisation Test (TPI), the Reiter Protein Complement Fixation Test (RPCFT), the Fluorescent Treponemal Antibody Test (FTA-ABS) and the Treponema Pallidum Haemagglutination Assay (TPHA), are discussed in detail. An evaluation of the results of the tests and the possible sources of errors are considered. The problem of the persistence of treponemes after clinically successful treatment is analysed and existing literature reviewed. The paper ends with a discussion of existing knowledge on protective immunity against infection with Treponema pallidum and a reminder of the need for further research into the immunology of syphilis.

Antibodies, Bacterial↗

[Therapy of sexually transmissible diseases].

Penicillin is still the drug of first choice for the treatment of Syphilis and Gonorrhoea. The therapy of infections with Treponema pallidum requires long lasting stabile blood and tissue levels, Neisseria gonorrhoeae can be eradicated by high serum concentrations of short duration. Chancroid and Donovanosis respond well to tetracylines, macrolide antibiotics and aminoglycosides while the application of sulfonamides or tetracyclines is suitable for the control of Lymphogranuloma venereum. Metronidazole or nimorazole derivatives may cure Trichomoniasis. Infections with Mycoplasmas (Urea-plasma) or Chlamydiae can be treated by tetracyclines only. Genital candidosis usually disappears after topical use of miconazole- or econazole- or clotrimazole-ointments. Herpes genitalis cannot be influenced by pharmacotherapeutical means, relapsing forms may be suppressed by vaccination. Mollusca contagiosa should be removed by the surgical spoon and genital warts can be destroyed by electrocautherization or by topical application of podophyllin solution.

Anti-Bacterial Agents↗

[Recent findings in the field of humoral immunology in syphilis].

Investigations on 404742 sera by the Automated Micro-Haemagglutination Assay with Treponema pallidum Antigen (AMHA-TP) and the VDRL-test for screening revealed 9848 (2,43%) reactive results in one of the two or in both methods. All reactive samples were checked by the FTA-ABS-test. A reactivity in both, the AMHA-TP and the FTA-ABS indicates a former infection with Treponema pallidum. The VDRL failed to point out reactivity in 4226 of 7474 sera (56,5%) deriving from syphilitic donors. The agglutination in the AMHA-TP can be inhibited by a protein of low molecular weight which occurs appearently in extraordinarily rare cases and was found in one sample only until now. The margin of error of the screening procedure by using the AMHA-TP and the VDRL amounts to 0,04%-0,38% of all samples examined.

Agglutination Tests↗

Clinical utility of a competitive ELISA to detect antibodies against Treponema pallidum.

Screening for Treponema pallidum infection is carried out on a large human population. To reduce costs, fewer tests which still offer adequate sensitivity and specificity could be performed. We studied the reliability of a novel indirect ELISA method to test for this infection. Several panels of sera were used that corresponded to 40 primary infections (group 1), 13 recurrences (group 2), 348 latent infections (group 3), 5 samples with anticardiolipin antibodies (group 4), 15 samples from patients with Lyme borreliosis (group 5), and 400 samples from blood donors and healthy pregnant women (group 6). The ELISA showed a global sensitivity and specificity of 100 and 99.5%, respectively. Our evaluation shows that Enzygnost Syphilis is a sensitive, specific, and simple test to screen for this infection.

Adult↗

Induction of acquired cellular resistance following transfer of thymus-dependent lymphocytes from syphilitic rabbits.

Syphilitic rabbits have previously been shown to resist challenge with Listeria monocytogenes. Thirty days after rabbits were infected with Treponema pallidum, transfer of 4 to 6 times 10-8 viable spleen cells along with T. pallidum conferred resistance to Listeria on normal recipients. Treatment of the spleen cells with anti-thymus serum and complement inhibited or abolished their ability to transfer resistance to Listeria. These results support the hypothesis that the ability of syphilitic rabbits to suppress the growth of Listeria reflects stimulation of cell-mediated immunity during active infection with T. pallidum.

Animals↗

Effect of passive immunization with purified specific or cross-reacting immunoglobulin G antibodies against Treponema pallidum on the course of infection in guinea pigs.

Whole immune serum or highly purified immunoglobulin G (IgG) antibodies to Treponema pallidum exhaustively adsorbed with three strains of nonpathogenic treponemes (TPI-IgG) were used for passive immunization of inbred strain 2 guinea pigs before and after intradermal challenge with 3.4 x 10(7) virulent T. pallidum Nichols organisms. Before challenge, control animals received a similarly purified IgG fraction containing either a cocktail of antibodies against three nonpathogenic treponemes (NPTI-IgG) or IgG prepared from normal guinea pig serum (NGPS-IgG). The purified fractions contained both IgG1 and IgG2 isotypes. The antibody levels (detected by fluorescent treponemal antibody test and enzyme-linked immunosorbent assay) and molecular specificities (immunoblot) of sera obtained from recipient animals before infection reflected those of the purified fractions used for immunization. Three protocols of passive immunization were used. Whole immune serum containing specific and cross-reacting antibodies afforded better protection than TPI-IgG even though asymptomatic animals were not fully protected. A single intradermal injection (0.1 ml) of TPI-IgG or NPTI-IgG into one hind leg 22 h before infection at the same site provided relatively higher protection than multiple intravenous injections (total, 15 ml) of the respective individual preparations. Since purified NGPS-IgG injected in the same animals, into the opposite hind leg, failed to protect against the challenging infection, it is reasonable to assume that specific and cross-reacting antitreponemal antibodies of the IgG1 subclass, which in guinea pigs are homocytotropic, play a relevant role in local protection.

Animals↗

["Old new" problem of the lues risk in transfusion medicine: the effect of the serum and ACD stabilizer at different temperatures on the infectiosity of Treponema pallidium (Nichols strain)].

The portion of warm and fresh blood transfusions had increased obviously. This is accompanied by a decrease of the restrictive period of the former 72 and the presently 48 hours for blood units to be transfused. Therefore, the danger of a symphilis transmitted by transfusion is impending again. This is realized insufficiently and the syphilis may occur, if blood is drawn in the seronegative phase of the primary stage of syphilis and transfused within the restrictive period. Model trials on the infectivity of Treponema pallidum revealed that the syphilis cannot be transmitted by blood and its derivates drawn in the seronegative phase after storage at 4 degrees C for 24 hours. Therefore, the reduction of the restrictive period to 48 hours is justified.

Animals↗

Intensive screening for gonorrhea, syphilis, and hepatitis B in a gay bathhouse does not lower the prevalence infection.

An attempt was made to reduce the rate of infection with Neisseria gonorrhoeae among homosexual men who visit a bathhouse in Denver, Colorado, by the offer of screening cultures during the 24 hr per week of maximal use of the bathhouse. A total of 543 men were screened (646 tests). The rate of infection did not decline significantly (P less than 0.80) from the first month (31 of 272 men; 11.4%) to the third month (19 of 180 men; 10.6%) of the program. Early syphilis was detected in five (0.8%) of 606 men and hepatitis B surface antigen in 13 (3.3%) of 389 men tested. Serologic evidence of prior infection with Treponema pallidum and hepatitis B virus was found in 96 (19.3%) of 498 and 226 (58.1%) of 389 men tested, respectively. It was concluded that patrons of a gay bathhouse have a high risk of contracting gonorrhea, syphilis, and hepatitis B. Although intensive screening is a cost-effective method of detecting cases of gonorrhea, the screening program did not reduce the prevalence of infection.

Gonorrhea↗