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Elevated serum Chlamydia trachomatis IgG antibodies. What do they mean for IVF pregnancy rates and loss?

OBJECTIVE: To evaluate the impact of elevated serum Chlamydia IgG antibodies (Ab) on in vitro fertilization (IVF) outcome in a large infertility population. STUDY DESIGN: One hundred ninety-four women under 40 years of age undergoing a total of 316 IVF cycles were evaluated. All couples with positive serum Chlamydia IgG Ab were pretreated with doxycycline, 100 mg twice daily, for 10 days prior to the first IVF cycle. RESULTS: One hundred seven women (55.2%) had elevated serum Chlamydia IgG Ab. One hundred seventy-two IVF cycles (54.4%) were in patients with elevated Ab as compared to 144 cycles (45.6%) in controls with negative Ab. There were no significant differences in mean age, number of mature oocytes obtained or number of embryos transferred between the two groups. Patients with elevated IgG Ab had on ongoing pregnancy rate of 30.2% (52/172) and implantation rate of 13.5% (101/746) as compared to 34.7% (50/144) and 13.6% (88/649) in the negative Ab group, respectively (P = NS for both). Two ectopic pregnancies occurred in the elevated Ab group (1.2%, 2/172) vs. none in the negative Ab group. The incidence of early pregnancy loss was 8.7% (15/172) and 9.7% (14/144) in the positive and negative Ab groups, respectively (P = NS). CONCLUSION: The prevalence of elevated serum Chlamydia IgG Ab in patients presenting for IVF was higher than in the general population. In the absence of an active genital tract infection, the presence of elevated serum Chlamydia IgG Ab was not associated with a poor IVF outcome when couples were treated with antibiotics prior to stimulation. In addition, there was no correlation between IVF outcome and quantitative IgG Ab titers in women with elevated serum Chlamydia Ab. We recommend that all couples with elevated titers be treated with doxycycline prior to the first IVF attempt to optimize pregnancy rates and minimize infectious complications.

Adult↗

[Polymerase chain reaction in the detection of patients infected by Chlamydia trachomatis after treatment].

OBJECTIVE: To investigate the value of polymerase chain reaction (PCR) for follow-up patients infected by Chlamydia trachomatis. METHODS: Follow-up specimens were collected from 30 patients. Chlamydia trachomatis positive were detected by PCR and direct fluorescence assay test (DFA) in the 30 patients before therapy. 15 patients were treated with minocycline (100 mg twice daily) for 10 days, and 15 patients were treated with 1.0 g of azithromycine as a single oral dose. RESULTS: After 1-2 weeks of antimicrobial therapy, all patients had negative DFA for Chlamydia trachomatis, but 9 had positive Chlamydia trachomatis DNA as detected by PCR. CONCLUSIONS: The 9 specimens were not confirmed to livae viable organisms of Chlamydia trachomatis. The debris of nonviable Chlamydia trachomatis DNA was excluded from urinogenital tract at about one month.

Adult↗

Secretion of cytokines by human synoviocytes during in vitro infection with Chlamydia trachomatis.

OBJECTIVE: Since Chlamydia-induced reactive arthritis is associated with the presence of viable chlamydiae in the synovial membrane, we studied the ability of Chlamydia trachomatis to stimulate a cytokine response by fibroblast-like synoviocytes in culture. METHODS: Fibroblast-like cells derived from biopsies of the synovial membrane were infected with Chlamydia trachomatis serotype E. Interleukin-6 (IL-6), transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) were determined using bio-assays. Granulocyte macrophage colony stimulating factor (GMCSF) was quantified by ELISA. RESULTS: Fibroblast-like synovial cells were capable of supporting chlamydial growth in vitro. Chlamydia trachomatis stimulated synoviocytes to produce IL-6, TGF-beta, and GMCSF. IL-1beta increased the production of IL-6 and GMCSF by mock-infected and infected cells. Treatment of synoviocytes with interferon-gamma resulted in the release of TNF-alpha in response to chlamydial infection. CONCLUSION: Chlamydia-induced cytokine release from synovial fibroblasts may contribute to alterations in the synovial membrane promoting the development of joint inflammation.

Bacteria↗

Chlamydia and sudden infant death syndrome. A study of 166 SIDS and 30 control cases.

Chlamydia inclusions could be demonstrated by an immunofluorescence assay in formalin-fixed lung sections in 32 of 166 cases (19.4%) of Sudden Infant Death Syndrome (SIDS) and in the lungs of only 1 of 30 infants with a known cause of death (3.3%). The difference is statistically significant (P = 0.04). Chlamydia trachomatis is an agent of pneumonia in 1-4 month-old infants who have acquired the disease from an infected cervix during birth, but other chlamydia species are also capable of causing pneumonia. The lung sections of the 32 chlamydia positive SIDS cases did not show typical histological signs of pneumonia. Even though chlamydia inclusions were detected in the lungs of 32 SIDS cases a causal relation between chlamydia infection and SIDS could not be demonstrated.

Age Distribution↗

ELISA for detection of human antibodies to Chlamydiae.

An enzyme-linked immunosorbent assay for the detection of human antibodies to Chlamydiae is described which exploits the cross-react properties between the genus-specific antigen of Chlamydiae and the ReLPS constituent of the outer membrane of a Salmonella minnesota mutant. Of 100 random sera tested by ELISA-ReLPS and immunofluorescence 78% showed an absolute correlation, 15% were positive in immunofluorescence and negative in ELISA and 7% were positive in ELISA and negative in immunofluorescence. Furthermore results obtained by the ELISA-ReLPS on 55 sera from patients with clinical evidence of Chlamydiae infection correlated well with the values obtained by an ELISA using Chlamydia-coated microtitration plates and by two immunofluorescence tests using Chlamydia trachomatis and Chlamydia psittaci as antigens. The method described here is sensitive, simple, reproducible and may be employed for epidemiological and pathogenetic studies of chlamydial infections.

Antibodies, Bacterial↗

Trypanosoma cruzi trans-sialidase as a new therapeutic tool in the treatment of chronic inflammatory diseases: possible action against mycoplasma and chlamydia.

The present paper proposes a new therapy using Trypanosoma cruzi trans-sialidase to treat diseases with unclear pathogenesis that present in common chronic inflammation and fibrosis. This hypothesis is based on recent findings that co-infection with mycoplasma and chlamydia is present in many of these diseases and that this enzyme was capable to eliminate or decrease the co-infection from the host. We identified that mycoplasmas and chlamydias are present in atherosclerosis, aortic valve stenosis, dilated cardiomyopathy, chronic chagasic myocarditis and cancer. We hypothetized that mycoplasmal infection may induce immunodepression in the host, favoring proliferation of pre-existent chlamydial infection and that elimination of mycoplasma would lead to improvement of the immune system resistance and the control of chlamydial proliferation. Mycoplasma has a particular parasitic relationship with host cells, involving strong adherence of their membranes, making it extremely difficult to eradicate mycoplasmal infection from the host. A new therapeutic approach is suggested using one or more agents that prevent or inhibit the adherence of mycoplasma to host cell membranes by removing sialic acid residues and preventing oxidation of the cells. The use of a neuraminidase enzyme, particularly the T. cruzi trans-sialidase enzyme, associated with treatment using anti-oxidating agents is proposed. Preliminary experimental animal and laboratory tests showed good results. The proposal that trans-sialidase from T. cruzi is efficient in combating co-infection of mycoplasma and chlamydia is based, at least in part, on the observation that chagasic patients suffering from T. cruzi infection present less mycoplasma and chlamydia infection in their tissues. Also, a lower incidence of the diseases above described to be related to mycoplasma infection is observed in chagasic patients. It is also hypothesized that co-infection with mycoplasma and chlamydia may induce oxidation of the host cells. Anti-oxidants such as those present in plant extracts may also be used in the treatment. Other diseases such as chronic hepatitis, glomerulonephritis, Multiple Sclerosis, Alzheimer's Syndrome and idiopathic encephalitis are other examples of chronic diseases where mycoplasma and chlamydia might be present, as they have the characteristics of unknown etiology, persistent chronic inflammation and fibrosis.

Animals↗

Detection of cervical Chlamydia trachomatis and Neisseria gonorrhoeae with deoxyribonucleic acid probe assays in obstetric patients.

OBJECTIVE: The Gen-Probe PACE 2 deoxyribonucleic acid probe assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae are targeted against the ribosomal ribonucleic acid of each pathogen. Our study compared the performance of the probe assays with culture for Chlamydia trachomatis (246 patients) and Neisseria gonorrhoeae (310 patients) while screening obstetric patients. STUDY DESIGN: Using culture as a gold standard, we assessed the sensitivity, specificity, positive predictive value, and negative predictive value of the chlamydia and gonorrhea probes. RESULTS: The prevalence of chlamydia by culture was 13.4% and gonorrhea 4.8%. Against culture, the chlamydia probe assay performed as follows: sensitivity 93.9%, specificity 99.1%, positive predictive value 93.9%, and negative predictive value 99.1%. Values for the gonorrhea probe assay were 93.3%, 99.0%, 82.4%, and 99.7%, respectively. Additional molecular analysis of probe-positive-culture-negative specimens suggests that the gonorrhea probe-positive predictive value may be even higher. CONCLUSION: The Gen-Probe PACE 2 deoxyribonucleic acid probe assays for chlamydia and gonorrhea appear to be promising as convenient, reliable, and cost-effective alternatives to conventional cultures in screening obstetric patients.

Adult↗

Evaluation of the Kodak Surecell Chlamydia test for the laboratory diagnosis of adult inclusion conjunctivitis.

PURPOSE: The Kodak Surecell Chlamydia test, a rapid enzyme immunoassay, has been reported to be highly sensitive (93%) and specific (96%) for detecting chlamydial lipopolysaccharide antigen in conjunctival specimens from infants, but has not been evaluated previously in adult conjunctival specimens. This study was designed to determine the efficacy of the Kodak Surecell Chlamydia test for the laboratory diagnosis of adult inclusion conjunctivitis. METHODS: Twenty Chlamydia culture-positive conjunctival specimens from adults (true-positives) and 20 true-negative specimens were tested with the Kodak Surecell Chlamydia test. RESULTS: The Kodak Surecell Chlamydia test was 40% (8/20) sensitive, 100% (20/20) specific, and 70% (28/40) efficient. CONCLUSIONS: This study indicates that the Kodak Surecell Chlamydia test, though highly specific, is less sensitive in its ability to diagnose chlamydial conjunctivitis in adults than has been reported previously in infants.

Adult↗

Antibiotic consumption and chlamydia prevalence in international studies.

BACKGROUND: To determine whether there is an ecological association between antibiotic use and chlamydia prevalence. METHODS: A systematic review was undertaken of international studies on chlamydia prevalence among women aged 15-25 years published between 2000 and 2005. Preference was given to studies using nucleic acid testing and representative population-based sampling methods. Data were obtained on per capita antibiotic consumption according to the defined daily dose. RESULTS: For the 12 countries for which both antibiotic consumption and relevant prevalence data for chlamydia were available, a non-significant negative correlation was found between total antibiotic consumption per capita and chlamydia prevalence among younger women according to country (r(s) = -0.242, P = 0.449). When an outlier (from the Netherlands) was excluded, the correlation was significant (r(s) = -0.615, P = 0.044). Combined use of tetracyclines and macrolides was also associated with lower chlamydia prevalence (r(s) = -0.697, P = 0.017). CONCLUSIONS: It is possible that antibiotics used for other reasons may have unexpectedly reduced the prevalence of chlamydia.

Adolescent↗

Comparative recoveries of chlamydia from urethral specimens using glass vials and plastic microtiter plates.

Urethral specimens known to contain Chlamydia were stored at -70 C in transport medium (2SP). For the test, circular glass coverslips were placed in the bottom of each culture vessel (glass shell vials and plastic microtiters plates [5 by 15 cm]) and seeded with McCoy's cells in medium containing 5-iodo-2-deoxyuridine. After 72 hours, cultures were inoculated with the specimens, and after 72 additional hours the monolayers on the coverslips were stained with iodine. Of 43 specimens, Chlamydia was recovered from 29 in glass vials but only from three in plastic plates (P less than .001). Chlamydia isolates could be passed serially only by vial-to-vial transfer; losses of 1,800 inclusion-forming units occurred after one subpassage from plates to either vials or plates. The extents of inactivation at 36 C of Chlamydia suspended in medium and placed in plastic plates and in glass vials were similar after seven hours. A substance toxic for Chlamydia could not be demonstrated in the plastic plates. Any new system for isolating Chlamydia from clinical specimens should be evaluated by comparison with culturing in glass vials.

Chlamydia↗

Chlamydia trachomatis antibody titres by enzyme-linked immunosorbent assay are useful in predicting severity of adnexal adhesion.

The aim of this study was to investigate the relationship between chlamydia infection and adnexal adhesion. A total of 131 infertile women who were otherwise asymptomatic underwent chlamydia antibody testing and laparoscopy. These women had additional infertility factors. Serum concentration of anti-Chlamydia trachomatis immunoglobulins G and A were determined prospectively by means of an enzyme-linked immunosorbent assay (ELISA). Results were compared with the tubal patency and severity of adnexal adhesion. Sensitivity, specificity, positive and negative predictive value, and likelihood ratios of anti-C.trachomatis antibody titres for the presence of adnexal adhesion were calculated. Patients who were positive for chlamydia antibody had a significantly higher incidence of tubal occlusion than those who were negative (47.1 versus 25.0%). Adnexal adhesion scores were significantly higher in the patients who were positive for chlamydia antibody than those in patients who were negative (17.1 versus 8.5). Adnexal adhesion scores were significantly correlated with anti-chlamydia antibody titre by ELISA [immunoglobulin (Ig) G: r = 0.60, Ig A: r = 0.61]. As the antibody titre by ELISA rose, the specificity, positive predictive value and the positive likelihood ratio all increased. In conclusion, C.trachomatis antibody testing is a simple and inexpensive means of predicting pelvic damage and laparoscopic examination may be recommended for patients with high anti-C.trachomatis antibody titres by ELISA.

Adnexal Diseases↗

Adolescent chlamydia testing practices and diagnosed infections in a large managed care organization.

GOAL: To determine chlamydia screening practices and the resulting positive test results for adolescents enrolled in a large nonprofit managed care organization. STUDY DESIGN: The electronic medical records of all 12- to 19-year-olds enrolled in a large nonprofit managed care organization serving a demographically diverse patient population from January 1998 through December 1999 were reviewed retrospectively. RESULTS: Among the 43,205 female and 44,133 male managed care organization members, ages 12 to 19 years in 1998-1999, 7575 adolescents (8.7%) (6914 females [16%] and 661 males [1.5%]) were tested for chlamydia. Among the members tested, chlamydia was diagnosed in 1109 adolescents (14.6%) (983 females [14.2] and 126 males [19.1%]); 761 (68.6%) adolescents were retested for chlamydia; and 182 (16.4%) had repeat positive test results. The median time to diagnosis of a repeat infection was 6 months. CONCLUSIONS: Chlamydia imposes a large disease burden in the private, organized healthcare sector. Managed care organizations can use operational data to enhance chlamydia prevention services by defining testing practices and local disease prevalence.

Adolescent↗

Phthirus pubis as a predictor for chlamydia infections in adolescents.

BACKGROUND: Providers not skilled in the evaluation of sexually transmitted infections (STIs) may treat pubic lice infestation without considering other organisms. This study compared the rate of chlamydia and gonorrhea infections in adolescents with and without pubic lice. GOAL: The goals of the study were to compare the rate of chlamydia and gonorrhea infections between adolescents infested or not infested with pubic lice and to evaluate lice infestation as a predictor for concurrent chlamydia or gonorrhea infection. STUDY DESIGN: A retrospective chart review of sexually active adolescents at a juvenile detention center in the Midwest between July 1998 and June 2000 was conducted. The index group was 62 adolescents with pubic lice screened for concurrent STIs. The control group included 201 randomly selected adolescents without pubic lice who underwent STI screening. RESULTS: In the entire study population (263 subjects), there were 60 cases of chlamydia (23% of all subjects) and 29 cases of gonorrhea (11%). Neisseria gonorrhoeae infection was present in 18% of index subjects and 9% of controls. Chlamydia trachomatis infection was noted in 39% of index subjects and 18% of controls. Pubic lice infestation predicted C trachomatis infection (odds ratio = 3.31). CONCLUSIONS: Pubic lice infestation is predictive of a concurrent C trachomatis infection in this population. Adolescents infested with pubic lice should be screened for other STIs, including chlamydia and gonorrhea.

Adolescent↗

The ribosomal intergenic spacer and domain I of the 23S rRNA gene are phylogenetic markers for Chlamydia spp.

Current methods used to classify Chlamydia strains, including biological, morphological, and DNA hybridization techniques and major outer membrane protein (omp1) gene analysis, can be imprecise or difficult to perform. To facilitate classification, 2.8-kb partial ribosomal DNA (rDNA) segments from a Chlamydia trachomatis strain and a Chlamydia psittaci strain were amplified by PCR and sequenced. Subsequently, a 1,320-bp region in this segment, including both the 16S/23S intergenic spacer (232 +/- 11 bp) and domain I (620 +/- 2 bp) of the 23S gene, was sequenced from 41 additional strains and from the chlamydia-like organisms Simkania sp. strains "Z" and "Z1." When both parsimony and distance analyses were performed, these sequences were found to have variable regions that grouped the isolates into two lineages (C. trachomatis and non-C. trachomatis) and nine distinct genotypic groups. The C. trachomatis lineage included human, swine, and mousehamster groups. The non-C. trachomatis lineage included Chlamydia pecorum, Chlamydia pneumoniae, and C. psittaci abortion, avian, feline, and guinea pig groups. These nine groups were essentially equidistant from the genetic root and were congruent with groups identified previously by using DNA-DNA homology, genomic restriction endonuclease analysis, host specificity, tissue specificity, and/or disease production. Phylogenetic trees based on the intergenic spacer or on domain I were congruent with trees previously derived from ompI sequences. DNA sequence analysis of either the intergenic spacer or domain I provides a rapid and reproducible method for identifying, grouping, and classifying chlamydial strains.

Animals↗

Nowhere near the point of diminishing returns: correlations between chlamydia testing and notification rates in New South Wales.

OBJECTIVE: To examine the relationship between chlamydia testing and chlamydia detection rates in New South Wales, Australia, from 1999 to 2001. METHODS: Correlations between population-based chlamydia testing and notification rates--stratified by age group, area of residence, and year--were determined by linear regression. RESULTS: Strong positive correlations between chlamydia testing and notification rates were observed for both women (r = 0.91, p < 0.001) and men (r = 0.94, p < 0.001). Between 1999 and 2001, the chlamydia test positivity rate increased from 4.3% to 7.3% for women (p < 0.0001) and from 7.8% to 10.5% for men (p < 0.0001). CONCLUSIONS AND IMPLICATIONS: This study suggests that Australia could benefit from a major chlamydia screening program.

Adolescent↗

Willingness to offer chlamydia testing in general practice in New South Wales.

OBJECTIVES: To assess willingness of general practitioners (GPs) to offer chlamydia testing to patients, and to identify demographic and practice correlates associated with willingness to offer chlamydia testing. METHODS: A postal survey of practising GPs in New South Wales was undertaken in 2002 to assess management of STIs in general practice. A 15% (n = 1,020) stratified random sample, based on sex and area of practice, was selected. The overall response rate was 45.4% (n = 409). RESULTS: More than four out of five study participants reported that chlamydia testing should usually be offered to patients who had recently changed sexual partners or inconsistently used barrier methods such as condoms. While 76% of GPs would like to offer testing to young women, 65% were in favour of testing young men. Just over half (56%) felt that chlamydia testing should usually be offered to patients at the time of a Pap smear. Multivariate analyses revealed that female GPs were more likely to offer testing to young patients and to female patients at the time of a Pap smear. GPs who had postgraduate training in STls had double the odds of offering testing to young men and to female patients at the time of a Pap smear. CONCLUSIONS AND IMPLICATIONS: This paper reveals variations in GPs' willingness to offer chlamydia testing to patients. Special education programs highlighting the adverse health effects of chlamydial infection have the potential to improve GP involvement in chlamydia screening.

Adult↗

Illuminating the evolutionary history of chlamydiae.

Chlamydiae are the major cause of preventable blindness and sexually transmitted disease. Genome analysis of a chlamydia-related symbiont of free-living amoebae revealed that it is twice as large as any of the pathogenic chlamydiae and had few signs of recent lateral gene acquisition. We showed that about 700 million years ago the last common ancestor of pathogenic and symbiotic chlamydiae was already adapted to intracellular survival in early eukaryotes and contained many virulence factors found in modern pathogenic chlamydiae, including a type III secretion system. Ancient chlamydiae appear to be the originators of mechanisms for the exploitation of eukaryotic cells.

Acanthamoeba↗

Effect of methylamine and monodansylcadaverine on the susceptibility of McCoy cells to Chlamydia trachomatis infection.

We used inhibitors of receptor-mediated endocytosis to study the mechanisms of infectivity, especially the uptake mechanism, of Chlamydia trachomatis for cultured cells. The effect of methylamine and monodansylcadaverine on the different stages of the chlamydial growth cycle in McCoy cells was examined. There was a dose-related decrease in the number of chlamydial inclusions in the presence of these agents. Monodansylcadaverine also decreased the chlamydia-dependent uptake of radioactive amino acids. The agents did not affect the attachment of chlamydiae to the cells, but they increased the protease-removable fraction of cell-bound chlamydiae. The amines reduced the number of inclusions when added at different times during the first 24 h of infection. However, this effect was influenced by host cell density, so that the effect of the amines at the early infectious phase was nullified in confluent monolayers, whereas, during later phases, the effect was comparatively independent of host cell density. This indicates that the amines have different modes of action at different infectious stages. The effect of the amines was reversible, and they had no effect on the infectivity of pretreated chlamydial elementary bodies. These experiments suggest that methylamine and monodansylcadaverine inhibit both the internalization of chlamydiae into McCoy cells and their intracellular development. These results are consistent with the hypothesis that chlamydiae utilize a constitutive cellular process, such as receptor-mediated endocytosis, to enter cells.

Amino Acids↗