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[Pleiotropic effect of the micronized fenofibrate: the reduction of plasma chlamydia pneumoniae antibody levels in patients with coronary artery disease].

INTRODUCTION: A growing amount of data suggest that atherosclerosis is an inflammatory disease and in it's development Chlamydia pneumoniae infection may contribute. Recent studies have shown that administration of micronized fenofibrate reduces the plasma levels of several markers of the inflammatory response. AIM: The aim of the authors was to evaluate the effect of micronized fenofibrate on the lipids and Chlamydia pneumoniae antibody levels of 20 patients with coronary artery disease. METHODS: The plasma total cholesterol, HDL-cholesterol, triglyceride, lipoprotein (a), ApoA1, ApoB, fibrinogen and Chlamydia Ig A, IgG and IgM antibody concentrations were examined. The patients were on strict lipid lowering diet and were treated by daily 200 mg micronized fenofibrate for 3 weeks. RESULTS: A significant reduction of the total cholesterol (18.3%), LDL cholesterol (17.7%), triglyceride (37.8%), ApoB (18.4%), fibrinogen (16.1%) levels was observed. The concentration of HDL cholesterol (17.0%) and ApoA1 (12.2%) showed a significant elevation. The Chlamydia pneumoniae IgM antibody (characterizing the acute infections) was not detectable. The IgA antibody level decreased from 13.0 EIU to 12.3 EIU (p < 0.05) and IgG from 85.1 EIU to 78.7 EIU (p < 0.05). CONCLUSIONS: Beside the expected lipid lowering effect of the micronized fenofibrate a significant reduction in the plasma Chlamydia pneumoniae IgA and IgG antibody levels was observed supporting the anti-inflammatory, pleiotropic effect of this drug.

Aged↗

[Chlamydia pneumoniae, atherosclerosis, and coronary disease].

There is an increasing body of evidence that links Chlamydia pneumoniae infections to atherosclerosis and the clinical complications of unstable angina, myocardial infarction and stroke. Several epidemiologic reports indicate an association between the presence and titer of Chlamydia pneumoniae antibodies and atherosclerosis and its complications. Other studies show the presence of Chlamydia pneumoniae, chlamydial antigens or nucleic acid in atherosclerotic plaques. Moreover, experimental studies present mechanisms by which Chlamydia pneumoniae may play a role in the induction of atherosclerosis and its complications. Finally, many studies have evaluated the effect of antibiotic treatment on cardiovascular events in humans. This article reviews all the aspects that link Chlamydia pneumoniae to atherosclerosis and its clinical manifestations.

Animals↗

Chlamydia pneumoniae antibodies and inflammatory reaction in patients with ischemic heart disease.

We studied the relationship between Chlamydia pneumoniae antibodies, C-reactive protein (CRP) and interleukine 8 (IL-8) in 87 patients with ischemic heart disease: 29 patients with acute myocardial infarction, 18 patients with unstable angina pectoris and 40 patients with stable effort angina. We determined in all patients IgG and IgA antibodies to Chlamydia pneumoniae, CRP and IL-8. Species specific antibodies to Chlamydia pneumoniae (IgG and IgA) were detected by indirect ELISA technique (Savyon Diagnostics Ltd, Israel). Interleukine-8 measured by a commercially available ELISA kit (CLB, Amsterdam, The Netherlands). CRP was determined by radial immunodiffusion (Mancini). The IgG antibodies were present in 25 patients (29%), the greatest percentage being noted in patients with unstable angina pectoris (50%). The IgA antibodies were present, as a sign of chronic Chlamydia pneumoniae infection, in 56% of the patients with IgG antibodies. CRP was positive in 52% of the 25 patients with positive IgG antibodies, but in only 34% of the 62 patients without IgG antibodies (p < 0.01). IL-8 was positive in 12% of the patients with IgG antibodies, and in 21% of the patients without IgG antibodies but the difference is not significant (p > 0.05). It is concluded that there is a relationship between the presence of the Chlamydia pneumoniae infection and inflammatory reaction in patients with ischemic heart disease, but the neutrophils are not implied in this process.

Adult↗

A study on immunopathogenetic mechanisms of atherosclerotic process caused by chronic infection of Chlamydia pneumoniae in rats (Ratus novergicus).

AIM: this study was aimed to determine the correlations between duration of Chlamydia pneumoniae infection and the development of atherosclerotic process in white-rats' (Ratus novergicus) aorta. METHODS: this is an experimental study which examined the expression of TNFa, IL-1b, IL-8, adhesion molecule of VCAM-1 and the development of foam cells associated with atherosclerotic process in white-rats' aorta. There were 32 male rats, +/- 6 weeks of age, divided into 4 groups: control group (K) without infection, and 3 groups with infection through nasal and oral inoculation of Chlamydia pneumoniae by single dose of 5 x 105 in amount of 35 microl. The first group (P1) was preserved for 5(1/2) months period, the second group (P2) was preserved for 7(1/2) months and the third group (P3) was preserved for 9(1/2) months. At the end of study, histological slides were made from aortic tissues in order to study the development of atherosclerotic process by examining foam cells and cytokines expression of TNFa, IL-1b, IL-8 and VCAM-1. Foam cells examination was performed by Hematoxcillin-eosin staining, while indirect immunohistochemistry staining was used to examine the expression of TNFa, IL-1b, IL-8 and VCAM-1. Afterward, the amount of foam cells and cytokines expression was measured. The study result was analyzed by ANOVA. RESULTS: there was increased expression of TNFa, IL-1b, IL-8, VCAM-1and increased foam cells formation (extended atherosclerosis area) in the aortic tissues infected by Chlamydia pneumoniae (5(1/2) months, 7(1/2) months and 9(1/2) months), which was significantly different compared to the control group. The result of ANOVA revealed that the most important factor in tissue injury is foam cells development induced by VCAM-1 and IL-8 in all of phases (characterized by most abundant neutrophil infiltration). It indicated the infection caused by extracellular pathogenic agent, which established the fatty streak (acute phase) in 5(1/2) months period. In the group with 7(1/2) months infection period, TNFa also had important roles (characterized by increased monocytes and lymphocytes infiltration), indicating that there was negative-gram pathogenic agent with intracellular infection, which caused a progressive atherosclerotic process, and development of fibrosis / atherosclerotic plaque (sub acute phase). In 9(1/2) months infection period, there was large thrombus containing a lot of leukocytes in the aorta (chronic phase). CONCLUSION: based on the result of this study, it may be concluded that Chlamydia pneumoniae may cause atherosclerotic process in aorta. Extracellular infection of Chlamydia pneumoniae occurs in all of phases and intracellular infection begins in sub-acute phase. On 5(1/2) months period, fatty streak is developed (acute phase); on 7(1/2) months period, there is atherosclerotic plaque (sub acute phase); and on 9(1/2) period, there is large thrombus containing a lot of leukocytes (a progressive chronic phase).

Animals↗

Response of goats to vaccination with temperature-sensitive mutants of Chlamydia psittaci obtained by nitrosoguanidine mutagenesis.

Two temperature-sensitive strains of ovine Chlamydia psittaci, 1B and 1H, obtained by mutagenesis were used as live-organism vaccines; 31 goats were given 4 X 10(6) plaque-forming units (PFU) of strain 1B, and 31 were given 5 X 10(6) PFU of strain 1H 2 months before they were bred. The consequences of the vaccination of the goats were studied during pregnancy by recording complement-fixation antibody titer, chlamydial excretion, and kidding performances and were compared with those of goats inoculated under the same conditions with 100 X smaller dose of virulent caprine abortive strain AC1. The vaccination did not disturb pregnancy, and none of the vaccinated goats excreted chlamydiae. In contrast, 2 of 28 goats inoculated with AC1 aborted and shed chlamydiae. One year after the goats were vaccinated, they were challenge exposed by intradermal inoculation of 10(6) PFU of the caprine strain AC1 at 79 to 98 days of pregnancy. Although 13 of the 14 control nonvaccinated goats aborted and excreted chlamydiae, none of the pregnant goats vaccinated with 1H and only 1 of the pregnant goats vaccinated with 1B aborted and excreted chlamydiae.

Animals↗

Transmission of Chlamydiae from grackles to turkeys.

Two female common grackles (Quiscalus quiscula) were inoculated intratracheally with 1.6 X 10(8) chick embryo lethal doses50 of a chlamydial organism isolated from turkeys. Eight female grackles were kept as uninoculated contacts. Six days later, two 12-week-old Broad-Breasted White turkeys (1 male and 1 female) were placed in the pen with the grackles. Chlamydiae were isolated in mice from cloacal swabs taken 14 days postinoculation from the infected grackles. Swabs from the contact grackles did not yield chlamydiae, nor did swabs taken 7 days later from all birds. Twenty-one days after being placed with the grackles, the turkeys developed signs of chlamydiosis. Cloacal swabs taken at 24 days yielded chlamydiae from only the female. Visceral organ tissues collected at 28 days from the male yielded chlamydiae. The only lesions in the turkeys at necropsy were enlarged spleens. The turkeys were serologically negative for chlamydial antibody both when placed and 15 days later, but were positive at days 24 and 28. These results indicate contact transmission of chlamydiae from infected grackles to turkeys.

Animals↗

[Pilot study of the occurrence of Chlamydia psittaci infections in commercial turkey flocks in Niedersachsen].

Turkeys from 8 commercial flocks, of which were 6 clinically healthy, were examined by use of enzyme-linked immunosorbent assay systems for genus-specific Chlamydia antigens and also for antibodies against Chlamydia psittaci in 4 flocks. Results of the tests indicate the presence of Chlamydia psittaci infections in all 8 flocks. The percentage of combined cloacal and conjunctival swabs positive for Chlamydia antigen ranged from 20-91% [20-70%] whereas the percentage of antibody-positive serum samples ranged from 81-100%. Our findings suggest, that the prevalence of Chlamydia psittaci infections in clinically healthy turkey flocks is higher than hitherto suspected.

Animals↗

The reprogrammed host: Chlamydia trachomatis-induced up-regulation of glycoprotein 130 cytokines, transcription factors, and antiapoptotic genes.

OBJECTIVE: Infection with Chlamydia trachomatis is a known cause of sexually transmitted diseases, eye infections (including trachoma), and reactive arthritis (ReA). Because the mechanisms of Chlamydia-induced changes leading to ReA are poorly defined, this study sought to identify the target genes involved at the molecular level. METHODS: Chlamydia-induced changes in host cells were investigated by combining a screening technique, which utilized complementary DNA arrays on C trachomatis-infected and mock-infected epithelial HeLa cells, with real-time reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay of gene products. Some responses were additionally demonstrated on human primary chondrocytes and a human synovial fibroblast cell line, both of which served as model cells for ReA. RESULTS: Eighteen genes (of 1,176) were found to be up-regulated after 24 hours of infection with this obligate intracellular bacterium, among them the glycoprotein 130 family members IL-11 and LIF, the chemokine gene MIP2-alpha, the transcription factor genes EGR1, ETR101, FRA1, and c-jun, the apoptosis-related genes IEX-1L and MCL-1, adhesion molecule genes such as ICAM1, and various other functionally important genes. In the context of this rheumatic disease, the cytokines and transcription factors seem to be especially involved, since various connections to chondrocytes, synoviocytes, bone remodeling, joint pathology, and other rheumatic diseases have been demonstrated. CONCLUSION: Infection with C trachomatis seems to reprogram the host cells (independent of activation by lipopolysaccharide or other ultraviolet-resistant bacterial components) at various key positions that act as intra- or intercellular switches, suggesting that these changes and similar Chlamydia-induced functional alterations constitute an important basis of the pathogenic inflammatory potential of these cells in ReA. Our results suggest that this approach is generally useful for the broad analysis of host-pathogen interactions involving obligate intracellular bacteria, and for the identification of target genes for therapeutic intervention in this rheumatic disease.

Apoptosis↗

A rapid chemiluminescent DNA hybridization assay for the detection of Chlamydia trachomatis.

With an estimated 3-4 million new cases per year, human infections from Chlamydia trachomatis are probably the most prevalent sexually transmitted disease (STD) in the United States. Diagnosis of Chlamydia is usually conducted by tissue culture methods. Direct immunofluorescence and ELISA tests have become available, but there remains a need for a test with better specificity and sensitivity. In response to this need, we have developed a rapid DNA hybridization assay using synthetic oligonucleotide probes to detect the presence of the Chlamydia trachomatis specific 7.4 kb plasmid. The assay involves solution phase hybridization of unlabelled probes, rapid capture of the probe-target duplex onto a microtitre dish surface, a new signal amplification technique that employs chemically cross-linked oligonucleotides, and an alkaline phosphatase labelled probe. Signal is obtained by reacting the labelled probe-target complex with an enzyme triggerable dioxetane substrate. Detection of the chemiluminescent output is performed either with a luminometer or by exposure to instant film. All 15 serovars of Chlamydia trachomatis react positively, while organisms known to co-inhabit the human urogenital tract react negatively.

Alkaline Phosphatase↗

Inhibition of intracellular multiplication of human strains of Chlamydia trachomatis by nitric oxide.

It was previously shown that murine T cell clones could inhibit the intracellular growth of the mouse strain of Chlamydia trachomatis by cytokine-mediated induction of the inducible nitric oxide synthase (iNOS) system in epithelial cells, an effect enhanced by direct epithelial-T cell interaction via specific adhesion molecules. These findings and other recent reports showing that human mucosal epithelial cells secrete nitric oxide (NO) via iNOS expression would suggest that mucosal epithelial-derived NO may be involved in mucosal defense against Chlamydia and other pathogens that infect epithelial cells. As an initial approach to investigating whether NO contributes to chlamydial control in humans, the present studies evaluated the susceptibility of human isolates of C. trachomatis to NO delivered by chemical donors or via induction of the epithelial iNOS system by a cytokine-secreting T cell clone. It was found that a chlamydial-specific, cytokine-secreting, murine T lymphocyte clone (clone 2.14-0) could inhibit the intraepithelial growth of human strains of Chlamydia trachomatis (serovar E and H, and Lymphogranuloma venerum type L2) via the iNOS pathway when the clone was co-cultured with chlamydial-infected epithelial cells. Furthermore, treatment of infected epithelial cells with 50 microM of the NO donor, S-nitroso-L-glutathione, resulted in significant inhibition (approximately 70%) of chlamydial multiplication, while the NO scavenger, myoglobin plus ascorbate, could reverse the effect, demonstrating that NO could directly inhibit human strains of Chlamydia. The results are consistent with the hypothesis that the IFN-gamma-inducible iNOS pathway can contribute to chlamydial control in humans.

Animals↗

Chlamydia ophthalmia neonatorum in Cameroon.

In the Ndoungué Hospital in Cameroon 449 new-born babies were examined for a month to check on the occurrence of ophthalmia neonatorum. Silver nitrate eyedrops 1% were applied at birth. The incidence of ophthalmia neonatorum was 19.4%; Chlamydia was found in 8 cases (incidence 1.8%) and gonococci in 4 cases (0.9%). Chemical conjunctivitis was suspected in 13 cases (2.9%). Slight conjunctivitis was seen in 68 cases and severe conjunctivitis in 19 cases (4.2%). A sexually transmitted agent was demonstrated in 6% of the slight cases and in 42% of the severe cases. Ophthalmia neonatorum due to Chlamydia was significantly more frequently severe and without specific features than those due to other agents. Although silver nitrate is still considered to be one of the most effective prophylactic measures for gonococcal ophthalmia neonatorum, in 4 cases this disease still developed. Silver nitrate is ineffective against Chlamydia and is also often the cause of a chemical conjunctivitis. The search is advocated for more efficient medicines in Africa which are effective against both Chlamydia and resistant gonoccoci.

Cameroon↗

Detection of Chlamydia trachomatis in urethral and urine samples from symptomatic and asymptomatic male patients by the polymerase chain reaction.

To evaluate the commercially available polymerase chain reaction (PCR) assay Amplicor (Roche Molecular Systems, USA) for diagnosis of Chlamydia trachomatis infection, urethral and urine swabs from a total of 344 male patients were tested and the results compared with those obtained by the nonisotopic hybridization assay Pace 2 (Gen Probe, USA) for urethral samples and by the enzyme immunoassay EIA MicroTrak (Syva, USA) for urine. Discrepant results were analyzed by a repeated test run using a major outer membrane protein-derived primer PCR, by the probe competition assay, and by the direct immunofluorescence test (DIF). Thirty-nine men (11.3%) were chlamydia positive, based on the results of all tests from both sampling sites. The rate of detection of chlamydia in urethral specimens by Amplicor and the Pace 2 was 79.5% and 61.5%, respectively, while the rate of detection in urine sediment was 75% for both Amplicor and EIA. In the first run of the PCR, a high number of false-negative results for unfrozen samples was observed, decreasing the sensitivity of Amplicor in urine to 47.3%. The results of the study indicate that Amplicor detects more infected individuals compared with other tests and is suitable as an alternative diagnostic test for chlamydia infections, using not only urethral specimens but also urine specimens. However, the finding of false-negative results when using Amplicor on unfrozen samples must be further investigated.

Bacteriuria↗

Prevalence of genital chlamydia and mycoplasma infection in couples attending a male infertility clinic.

To investigate the prevalence of genital mycoplasma (Ureaplasma urealyticum and Mycoplasma hominis) and Chlamydia trachomatis infections in infertile and fertile couples, 135 infertile couples from a male infertility clinic and 88 fertile couples from a prenatal care clinic were randomly screened. Semen, urethral and cervical smears were cultured for genital mycoplasma and chlamydia. Antichlamydia IgA, IgG and IgM antibodies were tested in blood and semen. Although the overall prevalence of Ureaplasma urealyticum was higher than that of Mycoplasma hominis, the prevalence of Mycoplasma hominis was significantly higher in the infertile men and women. The prevalence of Chlamydia trachomatis, positive culture was higher in infertile couples, but this difference was not significant. The prevalence of serum-specific IgG was significantly higher in infertile than in fertile women (11.9 vs 3.4%, p < 0.05). Specific semen IgA was significantly higher in infertile than in fertile men (8.9 vs 1.1%, p < 0.015). A low rate of concordance between partners was found in Mycoplasma and Chlamydia culture, and in the same patient between seminal IgA and urethral culture. In conclusion it is necessary to check both culture and serology findings in both partners.

Adult↗

Detection of Chlamydia trachomatis in asymptomatic women: relationship to history, contraception, and cervicitis.

The presence of Chlamydia trachomatis antigen was examined in 400 endocervical samples collected from an equal number of asymptomatic sexually active women. The overall prevalence was found to be 4%, using the enzyme-linked immunosorbent assay. Chlamydia infection was correlated with younger age (5.8%, p < 0.05), a history of pelvic inflammatory disease (30%, p < 0.0001), and more than four lifetime sexual partners (7.9%, p < 0.01). Women who used oral contraception had more infections (9.7%), than did women who used the intrauterine contraceptive device (4.8%, p > 0.05), condom (0%, p < 0.01) or no contraception (3.1%, p < 0.05). Infection was strongly associated with cervical erythema (8.2%, p < 0.0001), ectopy (7%, p < 0.05), friability (20%, p < 0.0001), and endocervical discharge (100%, p < 0.0001). These results support the view that Chlamydia trachomatis infection is associated with younger age, intense sexual life, and use of oral contraceptives. Given that the majority of infected women revealed cervical pathology, the detection of chlamydia in the high-risk female population with cervical changes seems to be essential.

Adolescent↗

Evaluation of urogenital Chlamydia trachomatis infections by cell culture and the polymerase chain reaction using a closed system.

Two hundred and fifty-four specimens from males and females consulting a clinic for sexually transmitted diseases were analyzed for genital Chlamydia trachomatis infection. Each clinical sample was tested by the cell culture technique and the polymerase chain reaction using a closed system. When the two test systems were compared, the overall sensitivity of the polymerase chain reaction was 96% and the specificity 94% when compared to the cell culture technique. By use of a closed system for DNA extraction and sample transfer for the polymerase chain reaction, contamination of the samples was minimized. The polymerase chain reaction detected a higher number of Chlamydia trachomatis infections among both symptomatic and asymptomatic females and males, and it also detected Chlamydia trachomatis at an earlier stage of infection when compared to cell culture. The polymerase chain reaction did not detect Chlamydia trachomatis after sufficient antibiotic treatment of the chlamydial infections.

Base Sequence↗

Efficacy of single-dose azithromycin versus doxycycline in the treatment of cervical infections caused by Chlamydia trachomatis.

The efficacy of single-dose azithromycin therapy in the treatment of cervical Chlamydia trachomatis infections was compared to that of a standard seven-day course of treatment with doxycycline. Cervical samples from 60 patients reacted positively in an enzyme immunoassay for detection of Chlamydia trachomatis. In 31 patients Chlamydia trachomatis was isolated from the sample taken before treatment. Fourteen of the 31 patients were treated with doxycycline and 17 with azithromycin. All cultures of samples taken one and four weeks after the start of therapy were negative. All 31 isolates showed a similar pattern of MICs for the seven antibiotics tested, including azithromycin and doxycycline. No differences were observed between isolates of different serovars. In samples from four patients chlamydial DNA could be detected by PCR one week after the start of the therapy and in two patients also after four weeks. No difference in microbiological parameters could be observed between the two treatment groups. It is concluded that single-dose azithromycin is as effective as a seven-day course of doxycycline in the therapy of cervical Chlamydia trachomatis infections.

Azithromycin↗

Evaluation of a chemiluminometric immunoassay for detection of Chlamydia trachomatis in the urine of male and female patients.

A chemiluminometric immunoassay (Magic Lite Chlamydia) for detection of Chlamydia trachomatis antigens in first-void urine samples was compared with cell culture using urogenital swabs from 221 men and 242 women. The rate of isolation of Chlamydia trachomatis was 23.5% in men, nearly 80% of whom had symptoms of urethritis, and 8.3% in women, in whom both cervix and urethra samples were tested. In urine sediments from men and women respectively the chemiluminometric assay showed a sensitivity of 80.8% and 70%, a specificity of 97% and 95%, a positive predictive value of 89.4% and 58.3%, and a negative predictive value of 94.3% and 97.2%. Discrepancies between results obtained with the chemiluminometric assay and cell culture were resolved using two polymerase chain reaction techniques to test urogenital samples. The detection of Chlamydia trachomatis in urine samples with the chemiluminometric assay was confirmed to be superior for screening symptomatic men with urogenital infections than women as a lower prevalence population.

Adolescent↗

Relationship between Chlamydia trachomatis infection and elevated serum immunoglobulin M levels in premature infants.

Serum immunoglobulin M (IgM) antibodies to Chlamydia trachomatis and to human cytomegalovirus (CMV) were detected by enzyme-linked fluorescence assay and enzyme-linked immunosorbent assay, respectively in 19 premature infants with chronic lung diseases, in 43 extremely low birth weight premature infants and in 123 neonates with elevated serum IgM levels. Ten of the 19 premature infants with chronic lung diseases had elevated serum IgM levels, and five had IgM antibodies to Chlamydia trachomatis. Three of the 43 extremely low birth weight premature infants had elevated serum IgM levels, and two had IgM antibodies to Chlamydia trachomatis. Three of the 123 neonates with elevated serum IgM levels (excluding those with chronic lung diseases and extremely low birth weight) had IgM antibodies to CMV. These results suggest that chronic lung diseases in low birth weight infants might be caused by intrauterine Chlamydia trachomatis infection.

Antibodies, Bacterial↗