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Incidence and reinfection rates of genital chlamydial infection among women aged 16-24 years attending general practice, family planning and genitourinary medicine clinics in England: a prospective cohort study by the Chlamydia Recall Study Advisory Group.

BACKGROUND: In England, screening for genital chlamydial infection has begun; however, screening frequency for women is not yet determined. AIM: To measure chlamydia incidence and reinfection rates among young women to suggest screening intervals. METHODS: An 18-month prospective cohort study of women aged 16-24 years recruited from general practices, family planning clinics and genitourinary medicine (GUM) clinics: baseline-negative women followed for incidence and baseline-positive women for reinfection; urine tested every 6 months via nucleic acid amplification; and behavioural data collected. Extra test and questionnaire completed 3 months after initial positive test. Factors associated with infection and reinfection investigated using Cox regression stratified by healthcare setting of recruitment. RESULTS: Chlamydia incidence was mean (95% CI) 4.9 (2.7 to 8.8) per 100 person-years (py) among women recruited from general practices, 6.4 (4.2 to 9.8) from family planning clinics and 10.6 (7.4 to 15.2) from GUM clinics. Incidence was associated with young age, history of chlamydial infection and acquisition of new sexual partners. If recently acquiring new partners, condom use at last sexual intercourse was independently associated with lower incidence. Chlamydia reinfection was mean (95% CI) 29.9 (19.7 to 45.4) per 100/person-year from general practices, 22.3 (15.6 to 31.8) from family planning clinics and 21.1 (14.3 to 30.9) from GUM clinics. Factors independently associated with higher reinfection rates were acquisition of new partners and failure to treat all partners. CONCLUSIONS: Sexual behaviours determined incidence and reinfection, regardless of healthcare setting. Our results suggest annual screening of women aged 16-24 years who are chlamydia negative, or sooner if partner change occurs. Rescreening chlamydia-positive women within 6 months of baseline infection may be sensible, especially if partner change occurs or all partners are not treated.

Adolescent↗

Chlamydia trachomatis: is it possible to reduce the number of infections after abortions?

In a study at the University Hospital in Trondheim during 1983, the frequency of Chlamydia trachomatis among women terminating their pregnancies was 8.2%. Younger women were infected by C. trachomatis at a more frequent rate than older women (p less than 0.001). Treatment of chlamydia-positive women was initiated within the first two weeks after the abortion. However, among women readmitted to the hospital, chlamydia-positive women showed a higher frequency of salpingitis than chlamydia-negative women (p less than 0.08). Preabortion examination for C. trachomatis and treatment of chlamydia-positive women by practitioners before the abortion is carried out, may reduce the postabortal frequency of salpingitis.

Abortion, Induced↗

Association between Chlamydia pneumoniae antibodies and intimal calcification in femoral arteries of nondiabetic patients.

BACKGROUND: Chlamydia pneumoniae, a gram-negative bacterium, has been suggested to be a risk factor for atherosclerosis. Calcium is a well-known component of atherosclerotic plaques, but it is uncertain whether infectious agents play a role in the calcification process of the arteries. PATIENTS: To address this issue we investigated the association of Chlamydia antibodies with intimal arterial calcification as assessed by soft tissue radiograms from the thigh region of 1373 nondiabetic Finnish individuals aged 45 to 64 years. RESULTS: At baseline, radiologically detectable intimal calcification in femoral arteries was found in 172 (27%) of 638 men and 43 (6%) of 735 women (P<.001). The presence of intimal artery calcifications was strongly related to conventional atherosclerotic risk factors and to Chlamydia antibodies. In Cox regression analysis, association of Chlamydia antibodies with intimal artery calcification persisted after extensive adjustment for other cardiovascular risk factors (P =.04). A dose-response relationship was observed between Chlamydia antibodies and intimal femoral artery calcification (P =.006). The presence of intimal artery calcification was strongly associated with an increased risk of future coronary heart disease mortality (P<.001). CONCLUSION: Chlamydia antibodies are strongly associated with intimal calcification of the femoral arteries.

Antibodies, Bacterial↗

Early atherosclerosis and Chlamydia pneumoniae infection in the coronary arteries.

In non-atheromatous segments of coronary arteries a sequence of preatherosclerotic changes was identified which consisted of medial thickening followed by intimal thickening. More recently, Chlamydia pneumoniae seropositivity was associated with enhanced intima-media thickness of arteries. In the present study the intimal and medial thickness of coronary artery of young adults were measured, and were correlated with the presence of Chlamydia pneumoniae antigens. Proximal and distal segments of the left anterior descending coronaries (LAD) obtained at autopsy from young adults (15-34 years) were studied. The thickness and cellular density of the intima and of the media without clear-cut atherosclerotic changes were measured by image analysis. The hypertrophy index was calculated as the ratio of cell density and the thickness of the respective layer. Atherosclerotic lesions occurring elsewhere in the same coronary were noted and graded by severity. The presence of Chlamydia pneumoniae verified by immunohistochemistry was correlated with the severity of lesions and with the hypertrophy index. In the proximal segments, atherosclerosis of LAD was associated with the widening of both the intima and the media of lesion free-sites. In the distal coronary segments the proportion of the intimal thickening had a significant association with atherosclerosis. Compared to non-infected arteries, Chlamydia pneumoniae infection was associated with higher hypertrophy index in the intima as well as in the media. The rate of Chlamydia pneumoniae positivity increased with the severity of lesions. As a conclusion: in the LAD coronary, the intimal thickening is the main preatherosclerotic change. Chlamydia pneumoniae may favour arterial wall hypertrophy and plays a role in lesion progression.

Adolescent↗

[No detection of Chlamydia pneumoniae in normal and atherosclerotic femoral arteries by polymerase chain reaction (PCR)--an autopsy study].

Since Saikku's investigations in 1988 a direct relation between atherosclerosis and infection with Chlamydia pneumoniae has been suspected. The aim of the present study was to examine histologically normal and atherosclerotic femoral arteries of autopsy cases and to correlate histological findings with the presence of Chlamydia pneumoniae which was tested with nested polymerase chain reaction. The study included all of the femoral arteries (of which 16 male, 15 female, aged between 50 and 88 years) obtained by autopsy from the cases occurring between July 1, 1999 and August 31, 1999 in the Medical Clinic Darmstadt. Each paraffin block supplied us with six consecutive sections of which the first two sectional areas were histologically stained, while the other four were used in PCR examination for DNA extraction. The polymerase chain reaction did not reveal presence of Chlamydia pneumoniae in any of the cases, neither in atherosclerotic lesions, nor in normal arteries. Because of the negative results, an additional PCR test was performed with primers that amplify another region of the Chlamydia genome, but the result did not change. The negative result of our prospective study does not contradict the assumption that infection with Chlamydia pneumoniae may enhance the progress of atherosclerosis in single cases. However, the results do not favour the concept of atherosclerosis as an infectious disorder caused by Chlamydia pneumoniae.

Aged↗

Simultaneous vaccination by three living attenuated strains of Brucella, Salmonella and Chlamydia in mice.

Associations of vaccines for simultaneous administration were successfully developed long ago, in particular in human medicine, although there have been very few attempts to associate living bacterial vaccines. Unfortunately, living vaccines can interact with one another resulting in either a virulent infection or an exclusion of one by the other. Having developed two new low virulence vaccinal strains of Chlamydia psittaci var. ovis and Salmonella abortus ovis for use in veterinary medicine, we studied associations of both and with the Brucella melitensis Rev1 vaccine in mice. There was no interaction between the Chlamydia and the Salmonella vaccines and between the Salmonella and the Brucella vaccines from the point of view of immunogenicity. In contrast, anti-Chlamydia immunity was decreased by about 15-19% when the Chlamydia vaccine was associated with the Brucella vaccine in double or triple association. Surprisingly, the Chlamydia vaccinal strain infection was slightly extended when administered in association. The simultaneous vaccination we tested could be of great interest in veterinary medicine, but special attention must be devoted to anti-Chlamydia immunity and would have to be studied in a ewe model.

Animals↗

Chlamydia pneumoniae IgG serological status and venous thromboembolism: a cross-sectional hospital based study.

OBJECTIVE: To search for a link between Chlamydia pneumoniae serological status and venous thromboembolic disease. METHODS: From March 1992 to October 1999, we conducted a cross-sectional hospital-based study of consecutive unselected outpatients referred to us for clinical suspicion of venous thromboembolism. We compared the Chlamydia pneumoniae serological status with respectively, the venous thromboembolism, the deep vein thrombosis and the proximal deep vein thrombosis status. RESULTS: Among 1193 patients registered for suspected venous thromboembolism, 1010 samples were available (499 negative and 511 positive patients for venous thromboembolism). Seventy-nine patients were Chlamydia pneumoniae positive. Our work failed to demonstrate any clear association between Chlamydia pneumoniae and venous thromboembolism status. Nevertheless, we identified a statistical difference regarding Chlamydia pneumoniae seropositivity and proximal vein thrombosis status (adjusted odds ratio of 1.70, CI95%: 1.05 to 2.77). CONCLUSION: The presence of Chlamydia pneumoniae antibodies might be a minor risk factor for venous thrombosis.

Aged↗

Sphingomyelin trafficking in Chlamydia pneumoniae-infected cells.

Chlamydia pneumoniae is a bacterial obligate intracellular parasite with a developmental cycle common to all members of the genus Chlamydia. Like other chlamydiae, the developmental cycle of C. pneumoniae occurs entirely within a membrane-bound intracellular vacuole, termed an inclusion, that is non-fusogenic with endosomal or lysosomal compartments. To characterize the vesicular interactions of the C. pneumoniae inclusion, we used a fluorescent analogue of ceramide, (N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproyl-Derythro-sphingosine (C6-NBD-Cer), that has previously been used to characterize the endogenous synthesis and transport of sphingolipids from the Golgi apparatus to Chlamydia trachomatis and Chlamydia psittaci inclusions. Sphingolipids are trafficked to C. pneumoniae inclusions in a time-, temperature- and energy-dependent manner with properties very similar to the delivery of sphingomyelin to C. trachomatis inclusions. These results indicate that interactions of the inclusion with a subset of sphingomyelin-containing exocytic vesicles is a property common to all species of chlamydiae.

4-Chloro-7-nitrobenzofurazan↗

Lymphocyte responses to Chlamydia antigens in patients with coronary heart disease.

AIMS: To clarify the relationship of Chlamydia pneumoniae infection and coronary atherosclerosis we studied cell-mediated and humoral immune responses to Chlamydia in 93 patients with angiographically confirmed coronary heart disease and in 115 controls without angiographically demonstrable lesions. METHODS AND RESULTS: Cell-mediated responses were analysed by measuring lymphocyte proliferative reactivity to whole elementary body antigens of C. pneumoniae. Control antigens included C. trachomatis and purified protein derivative of tuberculin. Chlamydia-specific antibodies were measured using microimmunofluorescence assay. Marked C. pneumoniae-specific immune reactivity, demonstrated by the high incidence of elevated IgG and IgA antibodies and strong lymphocyte proliferative response, was associated with coronary heart disease in male but not in female patients or controls. In male patients, the cell-mediated responses were strong to C. pneumoniae (median stimulation index 9,6) and to C. trachomatis (stimulation index 6,9). The females with coronary heart disease showed significantly stronger cell-mediated responses to C. pneumoniae (stimulation index 6,5) than to C. trachomatis (3,8; P < 0.001) and were comparable to the controls. CONCLUSION: Marked cell-mediated and humoral immunity to C. pneumoniae in males with coronary heart disease suggest that the immune mechanisms triggered by Chlamydia are a possible contributing factor in the disease pathogenesis of coronary atherosclerosis in males. The Chlamydia-specific cell-mediated responses seem to be predominantly induced by antigenic structures that are similar among different Chlamydia-species.

Antibodies, Bacterial↗

Detection of Chlamydia pneumoniae in liver transplant patients with chronic allograft rejection.

BACKGROUND: Chlamydia pneumoniae is one of the possible pathogenetic factors of atherosclerotic processes. Foam cell arteriopathy is a generally accepted pathologic feature of chronic liver allograft rejection and has several similarities to the early lesions of atherosclerosis. The aim of the authors' study was to show any existing correlation between the occurrence of Chlamydia pneumoniae and the presence of foam cell arteriopathy in transplanted livers with chronic rejection. METHODS: Ten liver samples from patients with chronic liver rejection including foam cell arteriopathy and 10 liver samples from healthy individuals were analyzed for the presence of Chlamydia pneumoniae by specific immunohistochemistry and polymerase chain reaction (PCR). Liver samples from two transplant patients with chronic liver rejection without any evidence of foam cell arteriopathy and nine patients with acute liver allograft rejection were also investigated by PCR. RESULTS: In all 10 rejected liver samples, Chlamydia pneumoniae was detected by PCR, whereas only one of the healthy control samples and one of the samples with acute rejection were found to be positive. Immunohistochemistry showed similar results. The positive signals of Chlamydia pneumoniae were localized mainly in the hepatocytes, sinusoidal and perisinusoidal cells, and the cells of portal tracts, whereas most of the altered hepatic arteries showed no or very weak positivity. CONCLUSIONS: The results strongly suggest an association between the occurrence of Chlamydia pneumoniae and the presence of foam cell arteriopathy in transplanted livers.

Adult↗

Polymerase chain reaction for the detection of Chlamydia psittaci in the feces of budgerigars.

The polymerase chain reaction (PCR) targeting the ompA gene of Chlamydia psittaci was evaluated for its ability to detect chlamydiae in fecal specimens of budgerigars as compared with isolation procedures using cell culture and embryonated egg inoculations. Several procedures for PCR template DNA preparation were compared so as to determine their detection levels for chlamydiae propagated in cell culture in the presence of fecal materials. Tween-20 and proteinase K treatments followed by centrifugation of the template DNA were found to be an appropriate procedure for DNA preparation for primary PCR. Subsequent nested PCR was shown to detect 4.8 IFU/ml or 84 particles/ml of chlamydiae. Chlamydiae in 50 fecal specimens from apparently healthy budgerigars were examined by nested PCR and several other methods. Nested PCR detected chlamydiae at a higher rate (12/50, 24%) than the isolation procedure in embryonated eggs (6/50, 12%). Primary PCR combined with the isolation procedure in cell culture gave a detection rate (5/50, 10%) similar to that of isolation from embryonated eggs. Detection rates by primary PCR (1/50, 2%) and in cell culture (0%) were inferior to the other procedures.

Animals↗

Pathogenic potential of novel Chlamydiae and diagnostic approaches to infections due to these obligate intracellular bacteria.

Novel chlamydiae are newly recognized members of the phylum Chlamydiales that are only distantly related to the classic Chlamydiaceae, i.e., Chlamydia and Chlamydophila species. They also exhibit an obligate biphasic intracellular life cycle within eukaryote host cells. Some of these new chlamydiae are currently considered potential emerging human and/or animal pathogens. Parachlamydia acanthamoebae and Simkania negevensis are both emerging respiratory human pathogens, Waddlia chondrophila could be a novel abortigenic bovine agent, and Piscichlamydia salmonis has recently been identified as an agent of the gill epitheliocystis in the Atlantic salmon. Fritschea spp. and Rhabdochlamydia spp. seem to be confined to arthropods, but some evidence for human exposure exists. In this review, we first summarize the data supporting a pathogenic potential of the novel chlamydiae for humans and other vertebrates and the interactions that most of these chlamydiae have with free-living amoebae. We then review the diagnostic approaches to infections potentially due to the novel chlamydiae, especially focusing on the currently available PCR-based protocols, mammalian cell culture, the amoebal coculture system, and serology.

Amoeba↗

Isolation and characterization of a gene encoding a Chlamydia pneumoniae 76-kilodalton protein containing a species-specific epitope.

Chlamydia pneumoniae is a human respiratory pathogen. Unlike the other two Chlamydia species, no species-specific antigen has been defined for C. pneumoniae. An immunoreactive clone containing a 0.8-kb fragment was isolated from a C. pneumoniae (AR-39) genomic library by using anti-C. pneumoniae rabbit immune serum. By Southern hybridization analysis of chromosomal digests of the different Chlamydia spp., the 0.8-kb fragment was shown to react specifically with C. pneumoniae. Subcloning of this fragment into the pGEX-1 lambda T expression vector resulted in the expression of a 62-kDa fusion protein. This fusion protein as well as the cleaved C. pneumoniae peptide were recognized by anti-C. pneumoniae rabbit immune serum, while the glutathione S-transferase moiety was not recognized. The fusion protein was used to produce monospecific rabbit antiserum. This antiserum was shown to react with a 76-kDa protein in all C. pneumoniae isolates tested, specifically recognize C. pneumoniae inclusions in tissue culture, and neutralize infectivity of C. pneumoniae in cell culture. No reactivity was observed with Chlamydia trachomatis or Chlamydia psittaci. To isolate the entire coding sequence of the 76-kDa protein, two partially overlapping fragments of C. pneumoniae DNA, a 3.2-kb HindIII fragment and a 1.2-kb PvuII fragment, were isolated, cloned, and sequenced. No significant sequence similarity was found with any previously reported nucleotide or amino acid sequence of the other Chlamydia species. This C. pneumoniae protein containing a species-specific epitope could play a role in pathogenesis and may be useful as a diagnostic tool.

Amino Acid Sequence↗

Cytokine-mediated indoleamine 2,3-dioxygenase induction in response to Chlamydia infection in human macrophage cultures.

The purpose of this study was to characterize further the events leading to the metabolic degradation of tryptophan in Chlamydia-infected cultures in the absence of added interferon (IFN). Macrophages on coverslips were infected with Chlamydia psittaci, and tryptophan decyclization was determined 24 h later by reverse-phase high-performance liquid chromatography. Tryptophan metabolites cochromatographed with kynurenine and N-formylkynurenine, the end products of tryptophan decyclization by the IFN-inducible enzyme indoleamine 2,3-dioxygenase (IDO). Although chloramphenicol pretreatment completely inhibited chlamydial replication, IDO was stimulated to an extent similar to that in untreated, infected cells. No IDO induction was observed in cells pretreated with cycloheximide even though chlamydial growth was slightly greater than in untreated cells. These results indicate that enhanced tryptophan decyclization was due to induction of IDO. IDO induction was dependent on the size of the chlamydial inoculum. Heat- or UV-inactivated chlamydiae induced significantly less IDO activity than viable chlamydiae. Culture supernatants from Chlamydia-infected macrophages induced IDO activity in a dose-dependent manner, suggesting that a secreted product of infected cells was responsible for IDO induction. A combination of neutralizing antibodies to IFN-alpha and IFN-beta inhibited induction of IDO activity by infected cell culture supernatants. Furthermore, IL-1 enzyme-linked immunosorbent assay results indicated the accumulation of IL-1 beta in the culture medium. Thus, induction of IDO in Chlamydia-infected macrophages reflects the production of cytokines in response to infection and may represent a normal host cell response to control intracellular infection.

Adult↗

[Formation of the selected biochemical markers in the patients with atherosclerotic arterial obliteration and the coexistent infection with Chlamydia psittaci].

In the arterial wall which is atheromatously changed both basic EB and reticular RB bodies of Chlamydia bacteria may be present. The role of these micro-organisms in the pathogenesis of arteriosclerosis is not thoroughly recognized yet. It is unknown whether Chlamydia initiate or lead to the inflammation of the already existent disease process. That is why it is expedient to carry out the research determining the correlation between the presence of Chlamydia bacteria in the operated arteries and the formation of the selected biochemical indicators. During the operation the imprint specimen was taken from the arterial wall, which was subsequently painted using stamp's method. EB bodies were marked in the immunofluorescence test with the usage of specific antibodies. The concentration of C-reactive protein was marked with the help of the rocket immunoelectrophoresis. The examination of blood lipids and fibrinogens was conducted with the usage of a colorimetric method with the help of ready-made kits. On the basis of the obtained data two groups of patients were distinguished. The first group comprised 16 patients (26%); here elementary EB bodies were detected both in the imprint specimens and the blood serum. In all the patients assigned to the first group the presence of anti-Chlamydia antibodies in the blood serum was observed. The second group consisted of the remaining 47 patients (74%); here no currently lasting Chlamydia infection was stated. On the basis of the conducted research and statistic calculations it is justified to point the correlation between the concentration of C-reactive protein and HDL cholesterol in the group of patients with the detected Chlamydia bacteria in comparison to the group of patients with no infection. However no statistically significant relationship between the concentration of fibrinogen, total cholesterol, LDL cholesterol and triglycerides was observed in the relation to the analyzed groups.

Aged↗

The tick-borne rickettsia Cowdria ruminantium has a Chlamydia-like developmental cycle.

The development of the tick-borne rickettsial pathogen Cowdria ruminantium (S stock) was studied in bovine umbilical endothelial (BUE) cell cultures and in goat choroid plexus, by light- and electron microscopy. Cowdria divided by binary fission within intracytoplasmic vacuoles resulting in large colonies of reticulate bodies. After three to four days in culture, reticulate bodies developed into smaller intermediate bodies characterized by an electron-dense core. Shortly before disruption of the host cells, intermediate bodies condensed further into electron-dense elementary bodies, which were released into the culture medium. Elementary bodies invade other endothelial cells thus initiating a new infectious cycle which lasts between 5 and 6 days. In the infected goat choroid plexus similar reticulate and intermediate bodies were identified within vacuoles of capillary endothelial cells. However, extracellular elementary bodies were not detected. Another stock of Cowdria (W) showed an identical developmental cycle as that of the S stock. The W isolate was also pathogenic for mice, making it possible to test the infectivity of reticulate and elementary bodies in these animals. Reticulate bodies appeared to be less infective than elementary bodies. The developmental cycle of Cowdria resembles the cycle known to occur in Chlamydia. Moreover, Cowdria has other similarities with Chlamydia. It has a Gram-negative envelope, it does not store iodine-stainable carbohydrates and may lack peptidoglycan as does Chlamydia. It is concluded, that Cowdria and Chlamydia are to a certain extent related, confirming a recent report that both organisms have certain antigenic determinants in common. Since Cowdria is also related to Ehrlichia it may well be that Cowdria takes an intermediate position between Chlamydia and Ehrlichia. The phylogenetic relationship between Cowdria and Chlamydia and also with Ehrlichia should be further elucidated by molecular analysis using 16S ribosomal DNA sequences.

Animals↗

Amplification of plasmid and chromosome Chlamydia DNA in synovial fluid of patients with reactive arthritis and undifferentiated seronegative oligoarthropathies.

OBJECTIVE: To investigate the hypothesis that whole bacteria might be found in the joints of patients with Chlamydia-associated reactive arthritis. METHODS: The presence of 2 plasmid- and 2 chromosome-specific sequences of Chlamydia DNA was investigated by amplification with the polymerase chain reaction, in synovial fluid (SF) samples from 71 patients with various arthropathies. RESULTS: Chlamydia DNA was found in SF samples from 22 patients. CONCLUSION: Whole chlamydiae are likely present in the SF of patients with Chlamydia-associated reactive arthritis.

Adolescent↗

Genome and proteome analysis of Chlamydia.

It has been difficult to study the molecular biology of the obligate intracellular bacterium Chlamydia due to lack of genetic transformation systems. Therefore, genome sequencing has greatly expanded the information concerning the biology of these pathogens. Comparing the genomes of seven sequenced Chlamydia genomes has provided information of the common gene content and gene variation. In addition, the genome sequences have enabled global investigation of both transcript and protein content during the developmental cycle of chlamydiae. During this cycle Chlamydia alternates between an infectious extracellular form and an intracellular dividing form surrounded by a phagosome membrane termed the chlamydial inclusion. Proteins secreted from the chlamydial inclusion into the host cell may interact with host cell proteins and modify the host cell's response to infection. However, identification of such proteins has been difficult because the host cell cytoplasm of Chlamydia infected cells cannot be purified. This problem has been circumvented by comparative proteomics.

Bacterial Physiological Phenomena↗