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PubMed1998

Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation.

We report that chlamydiae, which are obligate intracellular bacterial pathogens, possess a novel antiapoptotic mechanism. Chlamydia-infected host cells are profoundly resistant to apoptosis induced by a wide spectrum of proapoptotic stimuli including the kinase inhibitor staurosporine, the DNA-damaging agent etoposide, and several immunological apoptosis-inducing molecules such as tumor necrosis factor-alpha, Fas antibody, and granzyme B/perforin. The antiapoptotic activity was dependent on chlamydial but not host protein synthesis. These observations suggest that chlamydia may encode factors that interrupt many different host cell apoptotic pathways. We found that activation of the downstream caspase 3 and cleavage of poly (ADP-ribose) polymerase were inhibited in chlamydia-infected cells. Mitochondrial cytochrome c release into the cytosol induced by proapoptotic factors was also prevented by chlamydial infection. These observations suggest that chlamydial proteins may interrupt diverse apoptotic pathways by blocking mitochondrial cytochrome c release, a central step proposed to convert the upstream private pathways into an effector apoptotic pathway for amplification of downstream caspases. Thus, we have identified a chlamydial antiapoptosis mechanism(s) that will help define chlamydial pathogenesis and may also provide information about the central mechanisms regulating host cell apoptosis.

Animals↗
PubMed1999

Chlamydia inhibits interferon gamma-inducible major histocompatibility complex class II expression by degradation of upstream stimulatory factor 1.

We report that chlamydiae, which are obligate intracellular bacterial pathogens, can inhibit interferon (IFN)-gamma-inducible major histocompatibility complex (MHC) class II expression. However, the IFN-gamma-induced IFN regulatory factor-1 (IRF-1) and intercellular adhesion molecule 1 (ICAM-1) expression is not affected, suggesting that chlamydia may selectively target the IFN-gamma signaling pathways required for MHC class II expression. Chlamydial inhibition of MHC class II expression is correlated with degradation of upstream stimulatory factor (USF)-1, a constitutively and ubiquitously expressed transcription factor required for IFN-gamma induction of class II transactivator (CIITA) but not of IRF-1 and ICAM-1. CIITA is an obligate mediator of IFN-gamma-inducible MHC class II expression. Thus, diminished CIITA expression as a result of USF-1 degradation may account for the suppression of the IFN-gamma-inducible MHC class II in chlamydia-infected cells. These results reveal a novel immune evasion strategy used by the intracellular bacterial pathogen chlamydia that improves our understanding of the molecular basis of pathogenesis.

Cell Line↗
PubMed2000

Degradation of transcription factor RFX5 during the inhibition of both constitutive and interferon gamma-inducible major histocompatibility complex class I expression in chlamydia-infected cells.

We have previously shown that the obligate intracellular pathogen chlamydia can suppress interferon (IFN)-gamma-inducible major histocompatibility complex (MHC) class II expression in infected cells by degrading upstream stimulation factor (USF)-1. We now report that chlamydia can also inhibit both constitutive and IFN-gamma-inducible MHC class I expression in the infected cells. The inhibition of MHC class I molecule expression correlates well with degradation of RFX5, an essential downstream transcription factor required for both the constitutive and IFN-gamma-inducible MHC class I expression. We further demonstrate that a lactacystin-sensitive proteasome-like activity identified in chlamydia-infected cell cytosolic fraction can degrade both USF-1 and RFX5. This proteasome-like activity is dependent on chlamydial but not host protein synthesis. Host preexisting proteasomes may not be required for the unique proteasome-like activity. These observations suggest that chlamydia-secreted factors may directly participate in the proteasome-like activity. Efforts to identify the chlamydial factors are underway. These findings provide novel information on the molecular mechanisms of chlamydial evasion of host immune recognition.

Bacterial Proteins↗
PubMed2005

Human leukocyte antigen and cytokine gene variants as predictors of recurrent Chlamydia trachomatis infection in high-risk adolescents.

Antigen presentation and immune activation are essential to the effective control of infectious diseases. In 485 North American adolescents at high risk for genital Chlamydia trachomatis infection, we found 2 human leukocyte antigen variants (DRB1*03-DQB1*04 and DQB1*06) to be associated with recurrent Chlamydia infection (adjusted relative odds [RO], >2.0; P<.01, for both variants). A G-C-C haplotype corresponding to variants at IL10 (encoding interleukin-10 [IL-10]) promoter positions -1082, -819, and -592 was underrepresented in individuals with recurrent infection (RO, 0.59; P=.046). These genetic associations were independent of nongenetic factors, including number of sex partners, race, sex, duration of follow-up, and human immunodeficiency virus type 1 seropositivity. Consistent with the observed IL10 association, cervical secretions in female adolescents without the IL10 G-C-C haplotype had elevated IL-10 concentrations after Chlamydia infection, which may reflect involvement of a Chlamydia-specific mechanism for genetically mediated, differential IL-10 expression in the genital tract.

Adolescent↗
PubMed2006

'Blind' antibiotic treatment targeting Chlamydia is not effective in patients with MALT lymphoma of the ocular adnexa.

BACKGROUND: Recent results have implicated Chlamydia, especially Chlamydia psittaci, in the development of ocular adnexal lymphoma in the large majority of patients. We present our experience with ex-juvantibus antibiotic treatment in patients diagnosed with MALT lymphoma of the ocular adnexa. PATIENTS AND METHODS: A retrospective analysis identified a total of 11 patients (six female, five male) with MALT-lymphoma of the ocular adnexa who were given doxycyclin 200 mg p.o. daily over 3 weeks. Patients were tested also for autoimmune conditions, Helicobacter status and hepatitis along with assessment of MALT-lymphoma specific genetic changes. RESULTS: After a median follow-up of 9 months, none of the patients responded to 'blind' antibiotic treatment with doxycyclin. Only one patient with bilateral conjunctival lymphoma related a short lasting subjective improvement, but was referred to alternative therapy due to progression and worsening symptoms after 6 months. CONCLUSIONS: In this uncontrolled series, no effect of 'blind' antibiotic treatment with doxycyclin could be found in our patients with MALT lymphoma of the ocular adnexa. These results are in contrast to other series and suggest a potential geographic difference in the role of Chlamydia in ocular adnexal lymphoma. Thus, antibiotic therapy without prior testing for Chlamydia should be discouraged.

Adult↗
PubMed1993

Rapid diagnosis of Chlamydia psittaci pneumonia.

Two cases of Chlamydia psittaci pneumonia are presented. In each, a rapid diagnosis was made through the use of direct immunofluorescent antibody staining of respiratory secretions with monoclonal antibodies to chlamydial antigens. In one case the diagnosis was confirmed by the isolation of the causative organism from sputum and a pharyngeal swab. Chlamydial lipopolysaccharide was detectable in sputum from this patient in an enzyme immunoassay. Serological responses to C. psittaci, Chlamydia trachomatis, and Chlamydia pneumoniae were evaluated, and serological cross-reactivity was observed between each species. Rapid antigen detection systems for Chlamydia species that use commercially available reagents can be helpful in the evaluation of selected patient populations.

Antigens, Bacterial↗
PubMed1997

GP's management of genital Chlamydia: a survey of reported practice.

BACKGROUND: Genital chlamydial infection is the commonest curable sexually transmitted disease in the industrialized world. Little is known about how GPs manage this condition. OBJECTIVES: We aimed to determine current knowledge concerning genital chlamydia among GPs and to establish how patients with this infection are managed in primary care. METHODS: A confidential self-administered postal questionnaire survey was sent to all 494 GPs in one English health district (Leicestershire). RESULTS: Completed questionnaires were returned by 290 GPs (a response rate of 59%). A much higher proportion of GPs had tested and/or treated female patients for chlamydia [70%, 95% confidence interval (CI) 64-75%] as opposed to male patients (20%, CI 15-25%). Female patients (70%, CI 64-75%) were also more likely to be managed in general practice than male patients (56%, CI 50-62%). A majority of GPs (66%, CI 60-72%) routinely used an appropriate method of testing for chlamydia although a high vaginal swab, an inappropriate method of testing, was used by a fifth of GPs (19%, CI 15-24%). A large number of different treatment regimes were used by GPs. The majority of GPs (85%, CI 79-89%) prescribed an appropriate antibiotic although few GPs (19%, CI 14-25%) specified a chlamydia treatment regime in accordance with accepted international guidelines with respect to drug, dosage and duration of therapy. CONCLUSIONS: Female patients with known or suspected genital chlamydial infection are commonly managed in UK general practice. There is scope to improve the management of this infection in general practice.

Anti-Bacterial Agents↗
PubMed1997

Delivery of azithromycin to Chlamydia trachomatis-infected polarized human endometrial epithelial cells by polymorphonuclear leucocytes.

An in-vitro model was designed to evaluate whether polymorphonuclear leucocytes (PMN) loaded with azithromycin could migrate and deliver the antibiotic in a bioactive form to chlamydia inclusions in polarized human endometrial epithelial (HEC-1B) cells infected with Chlamydia trachomatis. PMN chemotaxis through the extracellular matrix and between infected epithelial cells was readily observed if the HEC-1B cells had been infected with chlamydiae for 36 or 48 h. Inclusions in infected epithelial cells exposed to PMN loaded with azithromycin were initially distinguished by deformed reticulate bodies and an excessive amount of chlamydial outer membrane vesicles. As the amount of PMN-delivered antibiotic increased, chlamydial inclusions were filled with large cell envelope 'ghosts' which were the remnants of lysed reticulate bodies. The lethal effect of azithromycin was confirmed by a reduction in the viability of infectious progeny. Our results demonstrate that the damage to chlamydiae was due to transport and delivery of azithromycin by PMN to infected genital epithelial cells. When infected HEC-1B cells were exposed to PMN not loaded with the antibiotic, chlamydial morphology was not obviously affected yet few viable progeny could be recovered. In this case, PMN-induced damage to host epithelial cells probably interrupted chlamydial nutrient acquisition and subsequent maturation and formation of infectious progeny.

Anti-Bacterial Agents↗
PubMed2003

Mutational analysis of the Chlamydia trachomatis dnaK promoter defines the optimal -35 promoter element.

A long-standing question in the biology of the intracellular bacterium, Chlamydia, has been the structure of the promoter recognized by its RNA polymerase. The 'RNA polymerase sigma subunit paradox' refers to the difficulty reconciling the conservation between the RNA polymerases of Chlamydia and Escherichia coli, especially at the level of the promoter-recognition sigma subunit, with the general lack of homology between chlamydial promoters and the E.coli sigma(70) consensus promoter. While the -10 promoter element appears to be conserved between Chlamydia and E.coli, the structure of the chlamydial -35 promoter element has not been defined. We have investigated the structure of the -35 element of the Chlamydia trachomatis dnaK promoter by measuring the effects of single base pair substitutions on in vitro promoter activity. Most substitutions produced large decreases in promoter activity, which allowed us to define the optimal -35 sequence in the context of the dnaK promoter. We found that the optimal chlamydial -35 promoter sequence is identical to the E.coli sigma(70) consensus -35 promoter element (TTGACA). These results indicate that the optimal promoter specificities of the major form of chlamydial RNA polymerase and E.coli sigma(70) RNA polymerase are in fact highly conserved. A further implication of our results is that many chlamydial promoters have a suboptimal promoter structure. We hypothesize that these chlamydial promoters are intrinsically weak promoters that can be regulated during the chlamydial developmental cycle by additional transcription factors.

Base Sequence↗
PubMed1999

An epidemic of a pertussis-like illness caused by Chlamydia pneumoniae.

BACKGROUND: Between June and July, 1994, we encountered an epidemic of a pertussis-like illness in adolescents in a junior high school located in a rural area of Japan. The purposes of this study were to record the clinical manifestations and to identify an etiology. PATIENTS AND METHODS: We interviewed patients and parents and we performed physical examinations on patients with cough during the epidemic. The chest radiographs were also reviewed by us. To identify an etiology we performed culture and serologic studies for a variety of bacteria, Mycoplasma, chlamydiae and viruses. Polymerase chain reaction (PCR) for Chlamydia pneumoniae was carried out on throat swab specimens. RESULTS: Of a total of 230 students 136 (59%) had severe cough illnesses. One developed pneumonia, 9 had bronchitis and the remaining 126 (93%) presented upper respiratory tract infections (URI). The mean duration of cough in cases with URI was 17.4 days and that in cases with bronchitis and pneumonia was 30.4 days. Serology and/or cultures for Bordetella pertussis, Bordetella parapertussis, Mycoplasma pneumoniae, Chlamydia trachomatis, Chlamydia psittaci or viruses were negative. Detection of C. pneumoniae infection was carried out in 46 patients with pneumonia, bronchitis or URI by serology and PCR. The patient with pneumonia, 7 of 7 patients with bronchitis and 32 (84%) of 38 patients with URI were documented to be infected by C. pneumoniae either by serology, PCR or both tests. CONCLUSION: An epidemic of a pertussis-like illness in a junior high school population was caused by C. pneumoniae.

Adolescent↗
PubMedDate not supplied

Oral sex as a risk factor for Chlamydia-negative ureaplasma-negative nongonococcal urethritis.

We present a case-control study that evaluated the association of Chlamydia-negative, Ureaplasma-negative nongonococcal urethritis with oral and/or anal sex. The study population was composed of 120 patients diagnosed as having nongonococcal urethritis in the Diagnostic Center for sexually transmitted diseases (STD) of the Medical School of Seville. Cases were 56 men suffering from nonogonococcal urethritis from whom neither Chlamydia trachomatis nor Ureaplasma urealyticum was isolated; the remaining 64 males with cultures positive for these agents were considered as controls. Insertive genital-oral intercourse significantly increased the risk of Chlamydia-negative, Ureaplasma-negative nongonococcal urethritis (odds ratio, 11.400; 95% confidence interval, 2.357-75.057). This association was still very strong (odds ratio, 8.882) after adjustment for homosexuality. Insertive anal intercourse appears not to increase the risk of Chlamydia-negative, Ureaplasma-negative nongonococcal urethritis. We conclude that insertive oral sex can be an important risk factor in the development of nongonnococcal urethritis in which the microbial agent is still unknown.

Chlamydia trachomatis↗
PubMedDate not supplied

Laboratory to laboratory variation in Chlamydia trachomatis culture practices.

GOAL OF THIS STUDY: To compare laboratory to laboratory variability in methods of cell culture for Chlamydia trachomatis performed by North American research laboratories. STUDY DESIGN: The authors administered a standardized 54-question survey to laboratories that had published articles in any of three medical journals reporting on the use of cell culture to identify individuals with C. trachomatis infection. Laboratory to laboratory variability in specimen collection, specimen transport conditions, culture methodologies, and criteria for evaluation of culture outcomes was examined. RESULTS: Twenty-five (93%) of 27 laboratories responded to the survey. Only two of 54 questions were answered uniformly by all responding laboratories. All laboratories reported vortexing or sonication of specimens before culture inoculation and centrifugation of inoculated cultures prior to incubation. In contrast, substantial variation was noted in specimen collection devices, specimen transport conditions and times, culture format, culture procedures, and criteria for identifying positive cultures. CONCLUSION: Although this study did not evaluate the sensitivity of chlamydia cell cultures performed in different laboratories, there was substantial laboratory to laboratory variation in nearly every facet of culture evaluated. Laboratory to laboratory variation in chlamydia cell culture sensitivity likely accounts for part of the substantial variability in published evaluations of the sensitivity of nonculture chlamydia diagnostic tests.

Bacteriological Techniques↗
PubMed1999

Establishing efficient partner notification periods for patients with chlamydia.

OBJECTIVES: To delineate chlamydia partner notification periods with high proportions of infected, untreated sexual partners, and to evaluate relevant Centers for Disease Control (CDC) recommendations. METHODS: Disease Intervention Specialists (DIS) offered contact tracing services to all chlamydia patients (N = 1,309) reported in Colorado Springs between July 1996 and June 1997. Patients were asked to identify sexual partners during the 180 days preceding treatment. Partners were actively sought by DIS and offered DNA amplification testing. RESULTS: Of 1,309 patients, 1,109 were interviewed, resulting in 2,293 named partners. Two fifths of eligible partners were located; inability to examine partners was related to time of last exposure and to frequency of sexual exposure. Of located partners, 95% were tested with DNA amplification technology. Adherence to CDC criteria identified 88% of infected, untreated partners; the other 12% consisted mainly of epidemiologically important asymptomatic men whose infection is seldom identified by current public health interventions. CONCLUSIONS: The chlamydia partner notification recommendations of the CDC are adequate, but miss men with long-standing infection. These men contribute to entrenched chlamydia endemicity; targeted programs to screen high-risk men merit serious consideration.

Adult↗
PubMed2003

Screening for Neisseria gonorrhoeae and Chlamydia trachomatis in men who have sex with men at male-only saunas.

BACKGROUND AND OBJECTIVES: In response to increases in sexually transmissible infections (STI) and HIV infection rates among men who have sex with men (MSM), the current study aimed to investigate the feasibility of a screening program at male-only saunas in Melbourne, Australia. GOAL: The goal was to determine (1) the participation rate, and the proportion whom obtain test results; (2) the prevalence of gonorrhea and chlamydia; and (3) to evaluate risk factors for STI acquisition. STUDY DESIGN: We used a cross-sectional design. Pharyngeal, rectal, and urethral specimens were collected from participants, and tested for Chlamydia trachomatis and Neisseria gonorrhoeae by polymerase chain reaction (PCR). RESULTS: There was a participation rate of 24% (n=521), and 70% obtained their test results. The infection rate in those who failed to collect their results was no different than those seeking theirs. The proportion of participants with PCR-detected gonorrhea and/or chlamydia infection was high, 10.7%. The presence of infection was associated with seeking sexual health care in the last year. CONCLUSION: The high prevalence rate of gonorrhea and chlamydia supports the concept of a screening program in Melbourne male-only saunas. The low participation rate has highlighted the need to consider alternative methods for making contact with men in the saunas or offering incentives to participate in future screening programs. Although anonymous participation encouraged participation for some men, future programs should attempt to obtain contact details for follow up of positive test results.

Adult↗
PubMed2004

Feasibility and short-term impact of linked education and urine screening interventions for Chlamydia and gonorrhea in male army recruits.

OBJECTIVE: The objective of this study was to assess the feasibility of an intervention for sexually transmitted diseases (STDs) and a screening program for Chlamydia trachomatis and Neisseria gonorrhoeae infections in male Army recruits. GOALS: The goals of this study were to identify and treat chlamydia and gonorrhea infections in recruits, assess their perceptions of risk, and increase their STD knowledge and behavioral intentions. STUDY DESIGN: Volunteers (n = 3911) entering basic training (July 1999-June 2000) at Fort Jackson, South Carolina, attended an educational intervention, completed pre- and post-questionnaires, and provided a urine specimen for chlamydia and gonorrhea screening by nucleic acid amplification testing. RESULTS: Chlamydia and gonorrhea prevalences were 4.7% and 0.4%, respectively. The mean STD knowledge score, intent to use condoms, and confidence in using condoms correctly increased (P <0.001). Participants reported increased risk perception and considered the educational program valuable (96.9%) and a learning experience (94.6%). CONCLUSIONS: A linked educational and screening program is feasible and acceptable in male Army recruits.

Adult↗
PubMed2006

Prevalence of Chlamydia in young men in the United States from newly implemented universal screening in a national job training program.

OBJECTIVE: The objective of this study was to examine chlamydia prevalence and its risk factors from the first universal screening in socioeconomically disadvantaged young men. GOAL: The goal of this study was to evaluate the need for universal screening in young men. STUDY DESIGN: We calculated chlamydia prevalence by demographic and geographic characteristics from 51,478 men aged 16 to 24 years who were screened from July 2003 to December 2004. RESULTS: Overall, chlamydia prevalence was 8.2%. Only 2.4% of the young men had sexually transmitted disease symptoms. Blacks had the highest prevalence (13.0%), whereas non-Hispanic whites had the lowest (3.1%). Men who smoked marijuana had a significantly higher prevalence compared with those who did not (11.9% vs. 6.4%). Men who used cocaine or PCP also had a significantly higher chlamydia prevalence compared with those who did not. Men who lived in the southern region of the United States had the highest prevalence. CONCLUSIONS: Chlamydial infection is highly prevalent among socioeconomically disadvantaged young men. Young men entering the National Job Training Program represent an important population for screening.

Adolescent↗
PubMed2006

A cost-effectiveness evaluation of a jail-based chlamydia screening program for men and its impact on their partners in the community.

BACKGROUND: Few cost-effectiveness evaluations of screening men in jails for chlamydia have been published, and none have evaluated the cost-effectiveness of providing partner notification services to the partners of chlamydia-infected inmates. GOAL: The goal of this study was to evaluate the cost-effectiveness of the chlamydia screening and partner notification programs for men conducted by a Massachusetts jail compared with 3 hypothetical alternatives. STUDY DESIGN: Using jail cost and testing data, we used decision analyses to compare the cost and effectiveness of universal screening, age-based screening with 2 age cutoffs, and testing of symptomatic inmates at intake using treated cases of chlamydia and gonorrhea as the primary outcome. We also evaluated the cost-effectiveness of adding partner notification to these alternatives. RESULTS: Universal screening was the most effective and expensive alternative. Age-based screening would have identified slightly fewer cases at half the cost of universal screening. The net cost of partner notification was low. Assuming high sequelae costs in female partners made partner notification a cost-saving intervention. CONCLUSIONS: Age-based screening could lower costs without substantially sacrificing effectiveness. Notifying partners of infected inmates was a cost-effective adjunct to screening inmates.

Adult↗
PubMed2026

Extragenital testing for gonorrhea and chlamydia in health department clinics in Virginia, 2018-2023.

BACKGROUND: Extragenital testing for chlamydia and gonorrhea infections is now routine in many settings. We assessed temporal and demographic trends in extragenital testing and positivity in public health department clinics in Virginia. METHODS: We analyzed urogenital and extragenital chlamydia/gonorrhea laboratory results for clients aged 15 years or older who attended 116 health department clinics from 2018 to 2023. Test volume and positivity was stratified by anatomic site, year, sex, and age. RESULTS: There were 181,471 client visits with valid test results. The proportion of visits with any extragenital testing increased from 19% to 46% during this time. Male clients were twice as likely as females to receive pharyngeal testing (46% vs. 22%) and five times as likely to be tested rectally (15% vs. 3%). Rectal specimen positivity surpassed urogenital positivity for chlamydia (females and males) and gonorrhea (males only). Overall, one-quarter of clients diagnosed with gonorrhea infections were identified exclusively through extragenital testing, as were 9% of clients with positive chlamydia tests. These proportions increased over time and were greater for younger clients and for males relative to females. Two-thirds of extragenital infections would have been missed by urogenital testing alone, including 40% and 49% of females and 86% and 73% of males with extragenital chlamydia and gonorrhea infections respectively. CONCLUSIONS: The proportion of clients who received extragenital chlamydia/gonorrhea testing increased over time, extragenital test positivity was high, and it identified infections that would have been missed otherwise. The impact on sexually transmitted infection sequelae and transmission remains unclear.

NAAT↗