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[The pathogenic role of Chlamydia trachomatis in otitis media with effusion].

There are conflicting views concerning middle ear infections due to Chlamydia trachomatis. To ascertain the etiological role of this agent in otitis media with effusion, middle ear effusions were cultured for C. trachomatis and other bacterial flora. A total of 102 patients with otitis media with effusion (OME) were recruited for this study. The study population included 66 patients with acute OME (AOME) and 36 patients with chronic OME (COME). As Chlamydia pneumoniae, the third species of Chlamydia, is also known to be isolated from middle ear effusion of OME, the fluorescent-antibody technique using anti-C. pneumoniae or anti-C. trachomatis antibodies was employed in order to identify the inclusion bodies isolated on HeLa 229 cells as C. trachomatis. C. trachomatis was recovered from 7 patients (10.6%) with AOME and from 8 (22.2%) patients with COME. Bacteria were cultured from 20 of 63 patients with AOME and from 13 of 28 patients with COME. Pathological bacteria were cultured from only 2 patients with C. trachomatis infection in the middle ear. Only normal skin flora, no bacterial pathogens, were isolated from the remainder. Antibodies to C. trachomatis in serum were measured by a microimmunofluorescent method in 13 patients with C. trachomatis infection in the middle ear. Antichlamydial antibody of the IgG type was detected in 84.6% (11/13) of these patients. These results suggest that C. trachomatis causes middle ear infections and plays an etiological role in the pathogenesis of otitis media with effusion.

Adolescent↗

GM-CSF transgene-based adjuvant allows the establishment of protective mucosal immunity following vaccination with inactivated Chlamydia trachomatis.

Cellular and humoral immune responses induced following murine Chlamydia trachomatis infection confer almost sterile protection against homologous reinfection. On the other hand, immunization with inactivated organism induces little protective immunity in this model system. The underlying mechanism(s) that determines such divergent outcome remains unclear, but elucidating the mechanism will probably be important for chlamydial vaccine development. One of the distinct differences between the two forms of immunization is that chlamydia replication in epithelial cells causes the secretion of a variety of proinflammatory cytokines and chemokines, such as GM-CSF, that may mobilize and mature dendritic cells and thereby enhance the induction of protective immunity. Using a murine model of C. trachomatis mouse pneumonitis lung infection and intrapulmonary adenoviral GM-CSF transfection, we demonstrate that the expression of GM-CSF in the airway compartment significantly enhanced systemic Th1 cellular and local IgA immune responses following immunization with inactivated organisms. Importantly, immunized mice had significantly reduced growth of chlamydia and exhibited less severe pulmonary inflammation following challenge infection. The site of GM-CSF transfection proved important, since mice immunized with inactivated organisms after GM-CSF gene transfer by the i.p. route exhibited little protection against pulmonary challenge, although i.p. immunization generated significant levels of systemic Th1 immune responses. The obvious difference between i.p. and intrapulmonary immunization was the absence of lung IgA responses following i.p. vaccination. In aggregate, the findings demonstrate that the local cytokine environment is critical to the induction of protective immunity following chlamydial vaccination and that GM-CSF may be a useful adjuvant for a chlamydial vaccine.

Adenoviruses, Human↗

A novel recombinant multisubunit vaccine against Chlamydia.

The administration of an efficacious vaccine is the most effective long-term measure to control the oculogenital infections caused by Chlamydia trachomatis in humans. Chlamydia genome sequencing has identified a number of potential vaccine candidates, and the current challenge is to develop an effective delivery vehicle for induction of a high level of mucosal T and complementary B cell responses. Vibrio cholerae ghosts (VCG) are nontoxic, effective delivery vehicles with potent adjuvant properties, and are capable of inducing both T cell and Ab responses in mucosal tissues. We investigated the hypothesis that rVCG could serve as effective delivery vehicles for single or multiple subunit chlamydial vaccines to induce a high level of protective immunity. rVCG-expressing chlamydial outer membrane proteins were produced by a two-step genetic process, involving cloning of Omp genes in V. cholerae, followed by gene E-mediated lysis of the cells. The immunogenicity and vaccine efficacy of rVCG-expressing single and multiple subunits were compared. Immunologic analysis indicated that i.m. immunization of mice with either vaccine construct induced a strong mucosal and systemic specific Th1 response against the whole chlamydial organism. However, there was an immunogenic advantage associated with the multiple subunit vaccine that induced a higher frequency of Th1 cells and a relatively greater ability to confer protective immunity, compared with the single subunit construct. These results support the operational theory that the ability of a vaccine to confer protective immunity against Chlamydia is a function of the level of Th1 response elicited.

Animals↗

Pneumonia associated with the TWAR strain of Chlamydia.

From November 1981 to August 1984, 301 adult patients with community-acquired pneumonia were admitted to the major referral hospital of Nova Scotia. Serologic tests done on these patients included microimmunofluorescence using the TWAR strain of Chlamydia and all Chlamydia trachomatis serovars as antigens. The TWAR strain has been shown to cause mild pneumonia in teenagers and young adults. Of the 301 patients, 18 (6%) had serologic evidence of recent infection with the TWAR organism. Their mean age was 64 years. Pneumonia associated with the presence of acute TWAR antibody had no characteristic clinical or radiographic features when compared with pneumonia without acute chlamydia antibody. Six patients, who all had preexisting serious chronic disease, had severe illness, and 2 died. Both patients who died had complicated hospital courses and other concomitant infections. We conclude that the TWAR organism may cause pneumonia in older adults and persons with chronic diseases that require hospitalization.

Adolescent↗

Screening for Chlamydia trachomatis in women 15 to 29 years of age: a cost-effectiveness analysis.

BACKGROUND: Clinical guidelines have traditionally advised annual Chlamydia trachomatis screening for women younger than 25 years of age. OBJECTIVE: To assess the cost-effectiveness of recently proposed strategies for chlamydia screening. DESIGN: State transition simulation model; cost-effectiveness analysis. DATA SOURCES: Published literature. TARGET POPULATION: Sexually active U.S. women 15 to 29 years of age. TIME HORIZON: Lifetime. PERSPECTIVE: Modified societal. INTERVENTIONS: Four strategies targeted to 3 specific age groups (15 to 19 years, 15 to 24 years, and 15 to 29 years): 1) no screening, 2) annual screening for all women, 3) annual screening followed by 1 repeated test within 3 to 6 months after a positive test result, and 4) annual screening followed by selective semiannual screening for women with a history of infection. OUTCOME MEASURES: Clinical events (for example, pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, and infertility), lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: Annual screening in women 15 to 29 years of age followed by semiannual screening for those with a history of infection was the most effective and cost-effective strategy. It consistently had an incremental cost-effectiveness ratio less than 25,000 dollars per quality-adjusted life-year (QALY) compared with the next most effective strategy. When the indirect transmission effects of a 10-year screening program on the probability of infection in uninfected women (that is, per-susceptible rate of infection) were considered, all strategies became more cost-effective. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the annual incidence of chlamydia, probability of persistent infection, screening test costs, and costs of treating long-term complications. Each variable was associated with threshold values beyond which screening became cost-saving. In probabilistic analysis, annual screening in women 15 to 29 years of age followed by semiannual screening for those with a history of infection had an incremental cost-effectiveness ratio less than 50,000 dollars per QALY in 99% of simulations. LIMITATIONS: Uncertainty about the natural history of chlamydial infection and consideration of only the indirect transmission effects of C. trachomatis screening. CONCLUSIONS: Annual C. trachomatis screening for all women 15 to 29 years of age and selective targeting of those with a history of infection for semiannual screening is very cost-effective compared with other well-accepted clinical interventions.

Adolescent↗

Endometritis related to Chlamydia trachomatis infection.

A 23-year-old woman had endometritis due to Chlamydia trachomatis infection. Chlamydia trachomatis was cultured from endometrial tissue obtained by biopsy, and elevated levels of serum antibodies, including IgM antibodies, to C. trachomatis were found. Cervical secretions were also positive for antibody. After treatment with tetracycline, endometrial cultures for C. trachomatis were negative and endometrial inflammation disappeared. Chlamydia trachomatis has been implicated in salpingitis, cervicitis, urethritis, and peritonitis, This case shows that endometritis may also result from C. trachomatis infection and in such instances may be a contributing factor in infertility.

Adult↗

Studies on the response of ewes to live chlamydiae adapted to chicken embryos or tissue culture.

Ewes infected before gestation with chicken embryo or tissue culture adapted chlamydial strain B-577 were challenge inoculated with the homologous strain at four to 18 weeks of gestation. The ewes responsed with group specific complement fixing antibody titers of 1:8 to 1:256 by the second week after initial infection. A secondary antibody response in the surviving challenge inoculated ewes occurred at the time of lambing and reached titers of 1:32 to 1:256 by the second week after parturition. Group specific complement fixing antibodies did not appear to play a significant role in resistance to chlamydial infection. Ewes infected with the chicken embryo adapted strain B-577 excreted chlamydiae in their feces 60 days after inoculation. However, chlamydiae were not recovered from feces of ewes infected with the tissue culture adapted strain B-577. Placentas of ewes challenge inoculated by the intravenous route were consistently infected. Chlamydiae were recovered from placentas, some fetuses and lambs. In two instances when challenge inoculation was given by the intramuscular route, infection was detected only by the direct fluorescent antibody method.

Animals↗

Clinical audit of the process of referral to genitourinary medicine of patients found to be chlamydia positive in a family planning service.

This paper describes a collaborative audit between a large family planning and genitourinary medicine (GUM) service undertaken to ensure that all women presenting for termination of pregnancy (TOP) or IUD fitting were offered screening for chlamydia, were informed of a positive result, and were subsequently referred to GUM for full sexual health screening and contact tracing. Over a six month period in 1996 1072 patients were seen for either TOP (763) or W1) fitting (309) and of these 999 were offered a test which was performed in 988. Overall 38 positive tests were reported (3.8 per cent) but only two of 259 patients tested prior to lUD fitting were found to have chlamydia (<0.8 per cent). Only 27 of these 38 women (74 per cent) had information recorded in their notes that they had been given their result and 24 patients (63 per cent) were seen in GUM. The audit uncovered problems with documentation and cross-referencing of information which largely accounted for the failure to reach some of the standards set. An action plan has been formulated in an attempt to improve this aspect of the screening service. If more widespread screening for chlamydia is to be effectively implemented as recommended by the 31st RCOG Study Group on the Prevention of Pelvic Infection, then it is of importance that workable local protocols are in place including arrangements for partner notification and treatment. This will involve close collaboration between a range of specialities working in the sexual health field.

Chlamydia Infections↗

[Abortive infection of mice inoculated intraperitoneally with Chlamydia ovis].

A mouse adaptated strain of Chlamydia ovis, when inoculated in the peritoneal cavity, caused the death of both pregnant and non pregnant mice. In addition, mice inoculated late in pregnancy (12 to 16 days after breeding) aborted 4 to 6 days after inoculation. Chlamydia was recovered from foetuses and from the organs of the mice (Liver, Spleen, Lungs). The severity of the disease was related to the inoculum concentration, so it was possible to induce late abortions with a rapid recovery of the females, like in the natural infection of the ewes. In the same conditions, the original Chlamydia strain maintained by passage on yolk sac, induced only an inapparent disease transmissible to the young mice.

Abortion, Veterinary↗

Chlamydia trachomatis cervicitis in gynecologic outpatients.

Symptoms suggestive of a lower genital tract infection (LGTI) are common complaints in women who consult gynecologists. Sexually transmitted microorganisms, such as Chlamydia trachomatis. Neisseria gonorrhoeae, and Trichomonas vaginalis, are responsible for a substantial proportion of LGTI. This study was performed to establish the frequency of LGTI caused by C trachomatis in women attending a gynecologic outpatient clinic. Of 170 women with LGTI, 32.9% harbored one or more of these organisms: C trachomatis was found in 19.3%, N gonorrhoeae in 4.7%, and T vaginalis in 25.9%. The results of the isolation studies were correlated with clinical signs and symptoms. In women under 25 years of age, chlamydial cervicitis was found significantly more often in users of oral contraceptives than in nonusers. In women not taking such drugs, cervical erosion was found more often in Chlamydia-positive than Chlamydia-negative women. Since clinical examination failed to reveal any characteristic signs in cases of chlamydial infection, it was not possible to distinguish a chlamydial from a gonococcal infection. This study also reports the successful treatment of 15 women affected by chlamydial cervicitis with doxycycline or trimethoprim sulphamethoxazole.

Adult↗

Elevated serum Chlamydia trachomatis IgG antibodies. Association with decreased implantation rates in GIFT.

OBJECTIVE: To analyze the impact of elevated Chlamydia IgG antibody (Ab) titers on the outcome of gamete intrafallopian transfer (GIFT) cycles. STUDY DESIGN: We retrospectively evaluated all the GIFT cycles in a five-year period performed at our center. One hundred one women under 40 years of age undergoing a total of 112 consecutive GIFT cycles were included. RESULTS: Twenty-six cycles (23.2%) were in women with elevated serum Chlamydia IgG Ab, and 86 (76.8%) were in women with negative titers. There were no significant differences in mean age, number of mature oocytes obtained or number of oocytes transferred between the two groups. Patients with elevated IgG Ab had clinical and ongoing pregnancy rates (PR) of 34.6% and 23.1%, respectively, and an implantation rate (IR) of 7.1% (13/184) as compared to a clinical and ongoing PR of 47.7% and 40.7%, respectively, and an IR of 16.5% (61/369) in the negative Ab group, respectively (P = NS for clinical and ongoing PR, P = .003 for IR). No ectopic pregnancies were noted in either group. The incidence of early pregnancy loss was 33.3% (3/9) and 14.6% (6/41) in the positive and negative Ab groups, respectively (P = .40). CONCLUSION: The presence of elevated serum Chlamydia IgG Ab was associated with a significantly lower implantation rate, a trend toward a lower PR and a trend toward a higher early pregnancy loss rate as compared to women with negative Ab titers. This group may represent a subset of assisted reproductive technology patients who are less likely to benefit from GIFT.

Adult↗

[Chlamydiae--still new surprises].

A review on participation of chlamydiae in the origin of the HIV-infection, carcinoma and atherosclerosis. The antibodies against the newly discovered pgp3 protein of C. trachomatis were found in 83-87% of the seropositive HIV patients. The participation of C. trachomatis in the etiology of cervical and ovarian carcinoma has been discussed in a number of articles. Simultaneous examinations along different lines allow the hypothesis, that C. trachomatis acts as a cofactor in the development of ovarian and cervical carcinoma. Chronic infection by C. pneumoniae appears to be one of the risk factors of pulmonary carcinoma. Many papers dealing with the relation of chlamydiae and atherosclerosis have been published. The relation between the chronic C. pneumoniae-infection and atherosclerosis has been assessed serologically and by direct demonstration of chlamydiae in atheromatous plaques.

AIDS-Related Opportunistic Infections↗

The role of Chlamydia trachomatis in patients with non-bacterial prostatitis.

The numbers of patients with chronic prostatitis are increasing in all countries. The aim of this study was to determine the prevalence of chlamydia in patients with non-bacterial prostatitis. Fifty-five patients suffering with back pain, discomfort on voiding and ejaculation and perineal ache, and 35 normal patients, were examined between December 1995 and July 1997. Urine samples and prostatic secretions after prostate massage were collected from all patients. Chlamydia antigens were tested for with Chlamyphast. Chlamydia antigen was positive in 14 of the 55 (25.4%) patients with non-bacterial prostatitis, but positive in only 2 (6%) patients in the control group. The difference between the two groups was statistically significant (p = 0.0268). After treatment with doxycycline 100 mg twice daily for 10 days, the clinic cure rate was 80%.

Chlamydia Infections↗

[The characteristics of local immunity in Chlamydia-associated chronic inflammatory diseases of the organs of the lesser pelvis in women].

Local immune reactions in 107 women with Chlamydia-associated chronic endometritis and salpingo-oophoritis were studied on endometrial biopsy specimens. Of these women, group 1 consisted 45 patients with Chlamydia-associated chronic endometritis and salpingo-oophoritis and group 2 consisted of 62 such patients having, in addition, bacterial vaginosis and candidiasis. Among associated bacteria, epidermal staphylococci, Escherichia coli and their combinations prevailed. Pathomorphologically, in the biopsy specimens taken from the patients of group 1 a decrease in the activity of mononuclear phagocytes, secondary SIgA deficiency with the level of IgA-producing plasmocytes relatively unchanged, the moderate intensity of the synthesis of IgG and a shift in the ratio of T-helpers/T-suppressors towards the latter were observed. In the biopsy specimens of the uterine mucosa obtained from group 2 a decrease in the phagocytic activity of neutrophil granulocytes and macrophages, the pronounced suppression of IgA production by IgA plasmocytes with a sharp decrease in the amount of SIgA and an essential increase in the number of IgG-producing cells were noted. Disturbances of local immunity, observed in the presence of associated Chlamydia infection, gives grounds for the inclusion of immunomodulating preparations into the complex of therapeutic measures.

Adult↗

Chlamydia trachomatis mouse pneumonitis lung infection in IL-18 and IL-12 knockout mice: IL-12 is dominant over IL-18 for protective immunity.

BACKGROUND: Interferon (IFN)-gamma is a key to protective immunity against a variety of intracellular bacterial infections, including Chlamydia trachomatis. Interleukin (IL)-18, a recently identified Th1 cytokine, together with IL-12 is a strong stimulator for IFN-gamma production. We investigated the relative roles of IL-18 and IL- 12 in protective immunity to C. trachomatis mouse pneumonitis (MoPn) infection using gene knockout (KO) and wild-type (WT) mice. MATERIALS AND METHODS: Mice were intranasally infected with C. trachomatis MoPn and protective immunity was assessed among groups of mice by daily body weight changes, lung growth of MoPn, and histopathological appearances at day 10 postinfection. The corresponding immune responses for each group of mice at the same postinfection time point were evaluated by measuring antigen-specific antibody isotype responses and cytokine profiles. RESULTS: Our results showed that IL-18 deficiency had little or no influence on clearance of MoPn from the lung, although KO mice exhibited slightly more severe inflammatory reactions in lung tissues, as well as reduced systemic and local IFN-gamma production, compared with WT mice. Results with IL-18 KO mice were in sharp contrast to those observed with IL-12 KO mice that showed substantially reduced clearance of MoPn from the lungs, substantial reductions of antigen-specific systemic and lung IFN-gamma production, decreased ratio of MoPn-specific immunoglobulin G (IgG)2a/IgG1, and severe pathological changes in the lung with extensive polymorphonuclear, instead of mononuclear, cell infiltration. Exogenous IL-12 or IL-18 was able to increase IFN-gamma production in IL-18 KO mice; whereas, only exogenous IL-12, but not IL-18, enhanced IFN-gamma production in IL-12 KO mice. Caspase-1 is the key protease for activation of IL-18 precursor into the bioactive form, and caspase-1 KO mice also displayed similar bacterial clearance and body weight loss to that in WT mice at early stages of MoPn infection. This further confirmed that IL-18 was not essential for host defense against chlamydia infection. CONCLUSIONS: These results suggest that IL-12, rather than IL-18, plays the dominant role in the development of protective immunity against chlamydia lung infection, although both cytokines are involved in the in vivo regulation of IFN-gamma production.

Animals↗

Role of Chlamydia trachomatis in epididymitis. Part II: Clinical diagnosis.

The aim of the research was to analyse the complaints and symptoms in acute Chlamydia trachomatis (C.t.) epididymitis. The analysis of data from history and physical examination was made in dependence on detected Chlamydia infection in the group of 39 patients with the symptoms of acute epididymitis (1--12 men C.t. (+), 2--27 men C.t.(-)). Chlamydial epididymitis more commonly occurred in younger patients, and the symptoms of the disease persisted for a longer time than in the patients with epididymitis of another etiology. None of the men had suffered from nongonorrhoeal epididymitis before, while two of them (16.7 percent) had had urethritis. The difference in etiology was also reflected in the patients' complaints. The discharge from the urethra was more common in the patients with Chlamydia infection (1--58.3 percent, 2--18.5 percent) while epididymis oedema and scrotum erythema where twofold scarcer. No exact correlation between C.t. presence and leukocyte reaction intensity in urethra was noticed. The occurrence of chlamydial epididymitis is not always preceded by symptoms of urethritis and only in some cases they are accompanied by the increase of polynuclear leukocytes in urethral discharge. Chlamydial epididymitis is of milder course when compared to epididymitis of another etiology.

Adolescent↗

The incidence of Chlamydia trachomatis in women with urethral syndrome.

The objective of this study was to discover the incidence of Chlamydia trachomatis in women with urethral syndrome. A total of 102 patients included in this study were divided into two groups: group 1 comprised 63 women suffering from painful urination and frequency, with no organisms seen on Gram stain or isolated in routine urine culture; group 2 consisted of 39 women with no complaints. Chlamydia antigen was found to be positive in 24 patient samples (38%) in group 1 and in four patient samples (11%) in group 2. The difference between the two groups was statistically significant (p = 0.0435). There was also a weak correlation between Chlamydia antigens and finding more than 10 polymorphonuclear leucocytes in the Gram stains (r = 0.02364).

Adult↗

Screening for chlamydia in general practice.

OBJECTIVE: To determine the prevalence of genital Chlamydia trachomatis infection in young patients presenting to general practitioners and to evaluate selective screening, based on risk factors, including gender. METHODS: A cross sectional survey of 508 consecutive patients aged 18-24, presenting to six general practices and one youth clinic in Mackay, North Queensland. We screened urine for chlamydia using Ligase chain reaction. RESULTS: Of 508 samples, 25 were positive (5%). The only factors with increased risks of infection were attendance at a youth clinic and recent change in sexual partner. It was as high in men as in women. CONCLUSION: Prevalence of chlamydia infection may be high enough to support screening of all patients aged 18-24, depending on cost effectiveness studies.

Adolescent↗