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PubMed2005

Accumulation of diacylglycerol in the Chlamydia inclusion vacuole: possible role in the inhibition of host cell apoptosis.

Intracellular pathogens have developed strategies to survive for extended periods inside their host cells. These include avoidance of host microbicidal effectors, often by sequestration in a protected subcompartment of the host cell. In some cases, the parasites exert also an antiapoptotic effect that prolongs the life of the infected host cell. Chlamydia utilizes both strategies, but the underlying molecular mechanisms are incompletely understood. Comparatively, little is known regarding the effects that Chlamydia exerts on the metabolism and distribution of the host cell lipids. The expression of fluorescently tagged C1 domains revealed that diacylglycerol is greatly accumulated in the immediate vicinity of Chlamydia inclusion vacuoles. The concentrated diacylglycerol recruits protein kinase Cdelta (PKCdelta), a proapoptotic effector, to the immediate vicinity of the vacuole. PKCdelta normally exerts its pro-apoptotic effects at the mitochondria and in the nucleus. We speculate that Chlamydia antagonizes the pro-apoptotic effect of PKCdelta by sequestering the enzyme on the inclusion vacuole away from its conventional target sites. Accordingly, we found that the ectopic expression of a catalytic fragment of PKCdelta that cannot be recruited by the vacuole, because it lacks a functional C1 domain, overcame the anti-apoptotic effect of the bacteria. The scavenging of pro-apoptotic factors may provide a novel mechanism whereby pathogens promote their own survival by extending the life of the host cells they infect.

Acetophenones↗
PubMed2006

Food for thought in women's health. The gynecologist: the new European gatekeeper in Chlamydia trachomatis infection.

Genital Chlamydia trachomatis infection is the principal cause of bacterial sexually transmitted disease in industrialized countries. A wide spectrum of pathologic conditions has been associated with the disease ranging from urethritis, cervicitis, to pelvic inflammatory disease, ectopic pregnancy, tubal infertility and cervical neoplasia. Screening for genital Chlamydia infection may prevent its serious complications. The need of a comprehensive European screening policy has been recently underlined by PACMeR's scientific committee. Anyhow invitational screening programs are only at the beginning. Chlamydia trachomatis control ''orphan'' and women's health at risk. Until organized programs are developed, implementation of opportunistic screening is mandatory. Since the infection is more commonly observed among juvenile females proper testing of the young women is recommended. As asymptomatic young women in reproductive age are more eager to visit gynaecologists for periodical gynaecological examination and councelling (cervical cytology, breast examination, contraception and family planning), gynaecologist represents the only specialist able to provide early diagnosis of Chlamydia trachomatis. Gynaecologists are called to play a new role in public healthcare, being ''gatekeepers'' for the early detection of the disease, emphasizing their crucial part in young women's health.

Adolescent↗
PubMed2005

Incidence of genital Chlamydia trachomatis infection in the male partners attending an infertility clinic.

Chlamydia trachomatis is an important pathogen in the aetiology of pelvic inflammatory disease, resulting in female infertility. If all female infertility patients are screened for silent genital chlamydia infection, should the male partners of these patients also be screened to decrease the risk of re-infection? To determine the incidence of current and present male infection with C. trachomatis, we carried out a prospective clinical study. We studied 100 consecutive new male partners of patients seen in the infertility clinic. The infertility was of at least 12 months duration. We used polymerase chain reaction detection of C. trachomatis in urine specimens and microimmunofluorescence serology was performed to detect both past and current infection. The female partners were also screened for chlamydia infection by cervical swabs and serology. In five male patients (5%) C. trachomatis DNA was detected in the urine specimen by polymerase chain reaction. Microimmunofluorescence serology was positive in five patients (5%). One of the subjects had positive serology and urine polymerase chain reaction testing. The proportion of male partners with current or previous C. trachomatis infection was therefore 9% (95% CI 3.39 - 14.60). Seven female patients had positive serology results (7%), one of whom also had a positive cervical swab result indicating current infection with the pathogen. In four cases, both the male and female partner had positive serology results. The cost of screening for C. trachomatis is cheaper than treating the complications of undiagnosed genital Chlamydia infection, which is implicated in tubal disease leading to infertility. The results suggest that routine screening of male partners in an infertility setting may be justified.

Adult↗
PubMed1989

Chlamydia trachomatis infection in a male college student population.

Male university students were studied to evaluate the merit of routine screening for chlamydia urethritis. Two hundred fourteen sexually active male students answered a questionnaire about symptoms of urethritis and exposure to and treatment for sexually transmitted diseases (STDs). All subjects were screened for chlamydia by enzyme immunoassay (Chlamydiazyme, Abbott Laboratories). Overall, Chlamydiazyme was positive in 42 of 214 subjects (19.6%). Eighty-six subjects had no symptoms and no history of untreated exposure to STD; 6 of these had positive Chlamydiazyme assays. Based on our results, we conclude that the proportion of male urethral chlamydia infections that are asymptomatic may be much higher than has previously been believed. We further conclude that asymptomatic sexually active male students on this campus are a high-risk population for whom routine chlamydia screening is appropriate.

Adolescent↗
PubMed1998

Vaccination against chlamydial genital tract infection after immunization with dendritic cells pulsed ex vivo with nonviable Chlamydiae.

Chlamydia trachomatis, an obligate intracellular bacterial pathogen of mucosal surfaces, is a major cause of preventable blindness and sexually transmitted diseases for which vaccines are badly needed. Despite considerable effort, antichlamydial vaccines have proven to be elusive using conventional immunization strategies. We report the use of murine bone marrow-derived dendritic cells (DC) pulsed ex vivo with killed chlamydiae as a novel approach to vaccination against chlamydial infection. Our results show that DC efficiently phagocytose chlamydiae, secrete IL-12 p40, and present chlamydial antigen(s) to infection sensitized CD4(+) T cells. Mice immunized intravenously with chlamydial-pulsed DC produce protective immunity against chlamydial infection of the female genital tract equal to that obtained after infection with live organisms. Immunized mice shed approximately 3 logs fewer infectious chlamydiae and are protected from genital tract inflammatory and obstructive disease. Protective immunity is correlated with a chlamydial-specific Th1-biased response that closely mimics the immune response produced after chlamydial infection. Thus, ex vivo antigen-pulsed DC represent a powerful tool for the study of protective immunity to chlamydial mucosal infection and for the identification of chlamydial protective antigens through reconstitution experiments. Moreover, these findings might impact the design of vaccine strategies against other medically important sexually transmitted diseases for which vaccines are sought but which have proven difficult to develop.

Adoptive Transfer↗
PubMed1998

Transmission of Chlamydia trachomatis and Neisseria gonorrhoeae among men with urethritis and their female sex partners.

Transmission of Chlamydia trachomatis and Neisseria gonorrhoeae among infected men and their female sex partners was examined using a design enhancing the likelihood that spread was directed from men to women. Chlamydia culture-negative specimens were examined using DNA amplification tests. Infection rates in women exposed to male sex partners with Chlamydia only were 65% (20/31) and with gonorrhea only were 73% (33/45). Infection of women by either agent was not influenced by the number of sexual exposures to or coinfection in men. There was a 98% (40/41) concordance of N. gonorrhoeae isolates among partners by auxotype and serovar. Chlamydia isolates were serotyped using ELISA and immunofluorescence testing and confirmed by nested polymerase chain reaction: 50% (6/12) of men and 57% (8/14) of women yielded mixed serovars. Sixty-four percent of pairs (9/14) were infected with identical serovars and an additional 28% shared at least one serovar. Multiple serovars of C. trachomatis, but not of N. gonorrhoeae, were common in sex partners and exchanged frequently.

Boston↗
PubMed2000

The microimmunofluorescence test for Chlamydia pneumoniae infection: technique and interpretation.

A brief description of current procedures for the Chlamydia microimmunofluorescence (MIF) test is presented. To date, use of MIF serology with Chlamydia pneumoniae (TWAR) antigen has provided the most sensitive and specific method for diagnosis of acute TWAR infection. In primary infections, the TWAR IgM antibody response is longer lasting and IgG antibody is slower to develop compared with Chlamydia trachomatis infection. Unlike other Chlamydia species, only a single serovar for C. pneumoniae has been recognized in the MIF system and cross-reaction with other species is negligible. While IgM antibody response is an important marker for serodiagnosis of acute infection, rheumatoid factor often causes false-positive reactions. Persistent TWAR IgG antibody has been useful for seroepidemiologic studies and an association of TWAR IgG antibody and atherosclerotic diseases has been observed. IgA antibody may not be a useful marker for chronic TWAR infection or for acute infection.

Adult↗
PubMed2003

Serologic evidence of past infection with Chlamydia trachomatis, in relation to ovarian cancer.

Pelvic inflammatory disease has been inconsistently linked with ovarian cancer. We measured antibodies to Chlamydia trachomatis, to chlamydial heat shock protein (CHSP) 60, and to CHSP10, in 117 women with ovarian cancer and in 171 age- and ethnicity-matched population-based control subjects from Oahu, Hawaii. IgG antibodies to serovar D of chlamydia elementary bodies (EB) and IgG antibodies to CHSP60-1, CHSP60-2, CHSP60-3, and CHSP10 were detected using an ELISA assay. The probability of having ovarian cancer was 90% greater in women with the highest, compared with the lowest (optical density, >or =0.40 vs. <0.10), levels of chlamydia-EB antibodies (P=.05). There was also a monotonic trend (P=.09) in ovarian cancer risk associated with CHSP60-1 but not with CHSP60-2, CHSP60-3, or CHSP10. These data suggest that past or chronic persistent infection with chlamydia may be a risk factor for ovarian cancer.

Adult↗
PubMed1980

Recovery of Chlamydia trachomatis from patients of southeastern venereal disease clinic.

The authors determined the incidences of Chlamydia trachomatis colonization obtained by use of two methods of isolation in 169 specimens from individuals attending a venereal disease clinic. Speciments were collected in phosphate sucrose buffer and planted simultaneously onto McCoy cells previously treated with 5-iodo-2-deoxyuridine (IUDR) and with cycloheximide. As controls, specimens were obtained from 76 hospital employees or medical students without clinical signs of infection and cultured in a similar manner. Qualitatively, recoveries of Chlamydia trachomatis inclusions from the differently treated cells were the same, but the number of inclusions per ml was greater for the cycloheximide-treated cells. Recoveries of Chlamydia trachomatis from the venereal disease clinic population were 33% for those patients who also had simultaneous culture positive for Neisseria gonorrhoeae and 42% for those with nongonococcal urethritis. The recovery of Chlamydia trachomatis from the control group was 5%.

Cells, Cultured↗
PubMed2005

Association of Chlamydia trachomatis with persistence of high-risk types of human papillomavirus in a cohort of female adolescents.

Human papillomavirus (HPV) infection is a necessary but not sufficient cause of cervical cancer. While chlamydia infection has been associated with cervical cancer, the meaning of this association remains unclear. The authors' objective was to investigate this association by evaluating whether concurrent genital tract infections are associated with HPV persistence, a precursor to cervical cancer. Interview data and biologic samples for HPV, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis testing were collected from female adolescents in an Atlanta, Georgia, longitudinal cohort study at 6-month visits (1999-2003). Associations with persistence (detection of the same HPV type at two sequential visits (visit pair)) were assessed among subjects with 2-5 visits and > or =6 months of follow-up. Associations were evaluated by logistic regression using methods for correlated data. Type-specific persistence of high-risk HPV types was detected in 77 of 181 (43%) analyzed visit pairs. Concurrent infection with C. trachomatis was independently associated with persistence of high-risk HPV types (adjusted odds ratio = 2.1, 95% confidence interval: 1.0, 4.1). Infection with more than one HPV type at the initial visit was also associated with high-risk persistence (adjusted odds ratio = 2.8, 95% confidence interval: 1.6, 4.9). The association between chlamydia infection and cervical cancer may be due to an effect of chlamydia infection on persistence of high-risk HPV.

Adolescent↗
PubMed1999

Ignorance about Chlamydia among sexually active women--a two centre study.

Chlamydia trachomatis is the micro-organism causing the most common sexually transmitted disease in the UK and Europe. The majority of female infections are asymptomatic and recognized sequelae include pelvic inflammatory disease, infertility, and ectopic pregnancy. Over 1200 sexually active women from two urban centres in the UK were questioned about awareness and knowledge of Chlamydia genito-urinary infection. Awareness was poor, as half of the study population had never heard of Chlamydia. Overall, less than one-quarter demonstrated adequate knowledge regarding transmission, immunity, symptoms, and sequelae. Better knowledge was found in women over the age of 25 years, in those cohabiting, in those with a professional/management occupation, and in those attending family planning clinics. The Chief Medical Officer's Expert Advisory Group on Chlamydia (1998) has recommended opportunistic screening of asymptomatic sexually active women in the UK. This study gives insight into the considerable task facing the Department of Health, as only an informed public will take up the offer of screening. Research is urgently needed to assess the impact of different approaches to education regarding sexually transmitted infection.

Chlamydia Infections↗
PubMed2004

Pre-exposure of infected human endometrial epithelial cells to penicillin in vitro renders Chlamydia trachomatis refractory to azithromycin.

OBJECTIVE: The clinical significance of the potential for persistent human chlamydial infections in vivo is being actively reassessed because of the increased frequency of recurrent infection with the same serovar despite compliance with an effective antibiotic regimen. The ability to extend the length of time of in vitro cultivation of polarized human endometrial epithelial cells (HEC-1B) provided the opportunity to establish a model system to determine if a persistent form of Chlamydia trachomatis had the same susceptibility as the actively growing form to a cidal concentration of azithromycin. METHODS: Polarized HEC-1B cells cultivated on extracellular matrix were infected with C. trachomatis serovar E and exposed to penicillin at 24 h post-infection (hpi) to induce a persistent infection characterized by slowly metabolizing but non-dividing, ultrastructurally aberrant reticulate bodies within the chlamydial inclusion; at 48 hpi, infected cultures were exposed to a bactericidal concentration of azithromycin for 72 h. RESULTS: Persistent chlamydiae were phenotypically resistant to azithromycin; the number of chlamydial inclusions on subpassage of progeny from persistent chlamydiae following removal of penicillin and recovery was essentially the same as from progeny from persistent chlamydiae following removal of penicillin and azithromycin and recovery. Neutrophils were attracted in vitro to persistently infected HEC-1B cells that had been exposed to penicillin and azithromycin. CONCLUSIONS: Thus, this study provides evidence at the cellular microbiology level in vitro for mechanisms that could exist in vivo to create sustained, but perhaps clinically inapparent inflammation, which might eventually lead to conditions such as silent pelvic inflammatory disease.

Anti-Bacterial Agents↗
PubMed2005

Serotonin and melatonin, neurohormones for homeostasis, as novel inhibitors of infections by the intracellular parasite chlamydia.

OBJECTIVES: Chlamydiae are obligate intracellular bacteria, causing a variety of diseases, i.e. pneumonia, sexually transmitted disease, conjunctivitis and zoonosis. Tryptophan depletion by interferon-gamma (IFN-gamma) is the most important host defence system against chlamydial infection. Thus chlamydial tryptophan metabolism is thought to play key roles for IFN-gamma resistance, persistent infection and host/tissue tropisms. We tested tryptophan derivatives for activity against chlamydia-infected cells. METHODS: Rates of chlamydial infection and sizes of the inclusions were evaluated by in vitro infection using three Chlamydiaceae species, Chlamydia trachomatis, Chlamydophila pneumoniae and Chlamydophila felis, which show significant divergence of tryptophan synthesis genes and different susceptibilities to IFN-gamma. RESULTS: Melatonin and serotonin, which are recognized as neural hormones for maintenance of organism homeostasis, reduced chlamydial infection but not other bacterial growth tested here. Unlike IFN-gamma, melatonin limited infection of all three chlamydiae and the effects were not recovered by tryptophan supplementation. Melatonin treatment only of host cells could diminish infection and the infection reduction was neutralized by a pertussis toxin, an inhibitor of G proteins. Ligands of melatonin and serotonin receptors also hampered infection. CONCLUSIONS: Inhibition mechanisms of chlamydial infection by melatonin and serotonin appear to be different from those of IFN-gamma and involve specific G-protein-coupled receptors. Melatonin is deemed to inhibit early progression of the chlamydial development cycle, such as establishment of intracellular infection and/or conversion from elementary body to reticulate body. Utilization of melatonin, serotonin or their derivatives may be advantageous for harmless prevention of chlamydial infection.

Anti-Bacterial Agents↗
PubMed1997

Evaluation of commercially available tests for Chlamydia nucleic acid detection in synovial fluid of patients.

Since the presence of Chlamydia nucleic acids has been shown in synovial fluid (SF) from some patients with Chlamydia reactive arthritis, we investigated whether commercially available tests, developed to detect Chlamydia nucleic acids in urogenital samples, could also be used for their detection in SF samples. We therefore tested SF samples, found positive with at least two different systems of DNA amplification in a previous study, with three commercially available kits. No positive results were obtained. It is concluded that the commercially available tests Gen-Probe PACE 2, Amplicor (developed by Roche Molecular Systems) and LCx (developed by Abbott Laboratories) do not have sufficient sensitivity to detect reliably Chlamydia RNA or DNA in SF.

Antibodies, Bacterial↗
PubMed2000

Chlamydia and associated arthritis.

An inflammatory arthritis is known to follow urogenital infection with the intracellular bacterium Chlamydia trachomatis in some individuals, and recent research results have elucidated important aspects of the characteristics of this Chlamydia-associated joint disease. Although the several extra-articular features of Chlamydia-induced arthritis have been defined clinically, their detailed causes remain largely unexplained. Current data indicate that the clinical characteristics of joint disease associated with C. trachomatis infection and those associated with postenteric arthritis are not easily distinguishable, although the response of each to antibiotic therapy does differ. The biologic characteristics of Chlamydia and enteric organisms in the joint show profound differences, and these are probably responsible for the variable responses to drug treatment. Molecular analyses of synovial C. trachomatis have demonstrated that long-term infection of the joint occurs primarily in synovial tissue and that the organism exhibits highly unusual biologic properties in its synovial context. These unusual molecular, biochemical, and other characteristics provide explanations for the frequent culture negativity of joint materials for C. trachomatis and for several other aspects of the arthritogenic process. Much remains to be learned concerning the behavior of this organism in the joint and concerning its interaction with its synovial host cells.

Anti-Bacterial Agents↗
PubMedDate not supplied

Susceptibility of Chlamydia trachomatis to antibiotics in vitro and in vivo.

The susceptibility of Chlamydia trachomatis to antibiotics was studied in vitro and in patients with nongonococcal urethritis. The minimal inhibitory concentrations of cloxacillin, erythromycin, pivampicillin, oxytetracycline, and doxycycline, which were the most effective drugs, were 10, 0.5, 0.25, 0.1, and 0.5 microgram/ml, respectively. The clinical observations suggested that of the antibiotics studied, doxycycline, erythromycin, and trimethoprim-sulfamethoxazole were effective for treatment of chlamydial infection and nongonococcal urethritis. Trimethoprim-sulfamethoxazole seemed less efficient for treatment of patients with nongonococcal urethritis whose cultures were chlamydia-negative. Pivampicillin, although it was active in vitro against C. trachomatis, did not produce a satisfactory clinical response. Untreated patients had symptoms of urethritis and chlamydial infection for three weeks. Incubation periods of a week or less were recorded for about half of the patients who had nongonococcal urethritis, both those whose cultures were chlamydia-positive and those whose cultures were chlamydia-negative. However, a few patients in both groups reported incubation periods of four weeks or more.

Adult↗
PubMed2000

Duration of untreated genital infections with chlamydia trachomatis: a review of the literature.

BACKGROUND: Estimates of the duration of untreated genital infections with Chlamydia trachomatis vary. Accurately estimating the distribution of the duration of infection would be useful in the counseling patients, and is essential when modeling the burden of chlamydial disease and the potential impact of prevention programs. GOAL: The authors review the scientific literature to summarize what is known about the duration of genital chlamydial infection and the factors that affect it. STUDY DESIGN: Literature review of animal and human studies. RESULTS: Animal studies document a longer duration of infection in primates than in mice or guinea pigs. Although animals spontaneously become culture negative over time, numerous studies document persistent nonculture evidence of chlamydiae in the upper genital tract. Studies in which women have been serially cultured suggest that most untreated infections remain culture positive for more than 60 days. Small series report that some infections may persist for years. Most infections eventually become culture negative; however, non-culture evidence of chlamydiae often persist in women with negative cultures. The duration of chlamydial infection is reduced in animals previously exposed to chlamydiae and in older humans, suggesting that partial immunity may result from exposure. Data are inadequate to define the median duration of untreated infection or to derive a curve that describes the natural history of untreated genital chlamydial infections. CONCLUSION: Current data do not allow one to reliably estimate the duration of genital infections with C trachomatis. Systematic retesting could help to better define the duration of infection in patients who, against medical advice, delay treatment for genital chlamydial infections.

Animals↗
PubMed2006

Internet-based screening for Chlamydia trachomatis to reach non-clinic populations with mailed self-administered vaginal swabs.

BACKGROUND: Testing for Chlamydia trachomatis by nucleic acid amplification tests (NAATs) using self-collected vaginal swabs (VS) is acceptable and accurate. The objectives were to implement an educational Internet-based program for women to facilitate home screening, to determine whether women would request and use self-collected VS kits, to determine associated risk factors for infection, and to determine satisfaction with the process. METHODS: The website, www.iwantthekit.org, was designed to encourage women > or =14 years to obtain home-sampling kits. Kits could be obtained in the community, requested by Internet/e-mail, or telephone. Users mailed the self-collected VS to the laboratory. Swabs were tested by 3 NAAT assays. Respondents called for results. RESULTS: Forty-one of 400 (10.3%) women were chlamydia positive; 95.1% were treated. Questionnaires indicated 89.5% preferred self-collection, 93.5% rated collection easy/very easy, and 86.3% would use the Internet program again. Black race and age <25 years were associated independently with being chlamydia positive, while use of birth control and non-consensual sex were protective. Thirty-six of 41 (87.8%) positive samples were positive by all 3 NAATs, 5/41 (12.2%) were positive by only 2 NAATs, and none were positive by only 1 NAAT. The Internet/e-mail request method was better than the community pick-up approach because 97.2% of kit requests were e-mailed and 87.5% of kits returned for testing were e-mail requested. CONCLUSIONS: Women will use the Internet to request and use home-sampling kits for chlamydia. NAAT testing performed well on dry-transported VS. High prevalence was detected and questionnaires indicated high-risk sexual behavior.

Adolescent↗