Studies on the response of ewes to live chlamydiae adapted to chicken embryos or tissue culture.
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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. (+info)
Chlamydia pneumoniae and atherosclerosis.
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OBJECTIVE: To review the literature for evidence that chronic infection with Chlamydia pneumoniae is associated with atherosclerosis and acute coronary syndromes. DATA SOURCES: MEDLINE and Institute of Science and Information bibliographic databases were searched at the end of September 1998. Indexing terms used were chlamydi*, heart, coronary, and atherosclerosis. Serological and pathological studies published as papers in any language since 1988 or abstracts since 1997 were selected. DATA EXTRACTION: It was assumed that chronic C pneumoniae infection is characterised by the presence of both specific IgG and IgA, and serological studies were examined for associations that fulfilled these criteria. Pathological studies were also reviewed for evidence that the presence of C pneumoniae in diseased vessels is associated with the severity and extent of atherosclerosis. DATA SYNTHESIS: The majority of serological studies have shown an association between C pneumoniae and atherosclerosis. However, the number of cases in studies that have reported a positive association when using strict criteria for chronic infection is similar to the number of cases in studies which found no association. Nevertheless, the organism is widely found in atherosclerotic vessels, although it may not be at all diseased sites and is not confined to the most severe lesions. Rabbit models and preliminary antibiotic trials suggest that the organism might exacerbate atherosclerosis. CONCLUSION: More evidence is required before C pneumoniae can be accepted as playing a role in atherosclerosis. Although use of antibiotics in routine practice is not justified, large scale trials in progress will help to elucidate the role of C pneumoniae. (+info)
Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population based study of coronary heart disease.
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OBJECTIVE: To study possible associations between coronary heart disease and serological evidence of persistent infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus. DESIGN: Population based, case-control study, nested within a randomised trial. SETTING: Five general practices in Bedfordshire, UK. INDIVIDUALS: 288 patients with incident or prevalent coronary heart disease and 704 age and sex matched controls. RESULTS: High concentrations of serum IgG antibodies to H pylori were present in 54% of cases v 46% of controls, with corresponding results for C pneumoniae seropositivity (33% v 33%), and cytomegalovirus seropositivity (40% v 31%). After adjustments for age, sex, smoking, indicators of socioeconomic status, and standard risk factors, the odds ratios (95% confidence intervals) for coronary heart disease of seropositivity to these agents were: 1.28 (0.93 to 1.75) for H pylori, 0.95 (0.66 to 1.36) for C pneumoniae, and 1.40 (0.96 to 2. 05) for cytomegalovirus. CONCLUSIONS: There is no good evidence of strong associations between coronary heart disease and serological markers of persistent infection with H pylori, C pneumoniae, or cytomegalovirus. To determine the existence of moderate associations between these agents and disease, however, larger scale studies will be needed that can keep residual confounders to a minimum. (+info)
Nongonococcal urethritis--a new paradigm.
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Urethritis in men has been categorized historically as gonococcal or nongonococcal (NGU). The major pathogens causing NGU are Chlamydia trachomatis and Ureaplasma urealyticum. Trichomonas vaginalis may be involved occasionally. In up to one-half of cases, an etiologic organism may not be identified. In this review we present recent advances in the diagnosis and management of NGU and discuss how they may be applied in a variety of clinical settings, including specialized STD clinics and primary health care practices. In particular, the development of the noninvasive urine-based nucleic acid amplification tests may warrant rethinking of the traditional classification of urethritis as gonococcal urethritis or NGU. Diagnostic for Chlamydia are strongly recommended because etiologic diagnosis of chlamydial urethritis may have important public health implications, such as the need for partner referral and reporting. A single 1-g dose of azithromycin was found to be therapeutically equivalent to the tetracyclines and may offer the advantage of better compliance. (+info)
Chlamydia infections and heart disease linked through antigenic mimicry.
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Chlamydia infections are epidemiologically linked to human heart disease. A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice. Injection of the homologous Chlamydia peptides into mice also induced perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart, as well as triggering T and B cell reactivity to the homologous endogenous heart muscle-specific peptide. Chlamydia DNA functioned as an adjuvant in the triggering of peptide-induced inflammatory heart disease. Infection with C. trachomatis led to the production of autoantibodies to heart muscle-specific epitopes. Thus, Chlamydia-mediated heart disease is induced by antigenic mimicry of a heart muscle-specific protein. (+info)
The in-vitro activity of HMR 3647, a new ketolide antimicrobial agent.
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The in-vitro activity of HMR 3647, a novel ketolide, was investigated in comparison with those of erythromycin A, roxithromycin, clarithromycin (14-membered ring macrolides), amoxycillin-clavulanate and ciprofloxacin against 719 recent clinical Gram-positive, Gram-negative and anaerobic isolates and type cultures. HMR 3647 generally demonstrated greater activity than the other compounds with MIC90s of < or =0.5 mg/L, except for Staphylococcus epidermidis (MIC90 > 128 mg/L), Haemophilus influenzae (MIC90 = 2 mg/L), Enterococcus faecalis (MIC90 = 2 mg/L), Enterococcus faecium (MIC90 = 1 mg/L) and the anaerobes, Bacteroides fragilis (MIC90 = 2 mg/L) and Clostridium difficile (MIC90 = 1 mg/L). In general, an increase in the size of the inoculum from 10(4) to 10(6) cfu on selected strains had little effect on the MICs of HMR 3647. Additionally, the in-vitro activity of HMR 3647 was not affected by the presence of either 20 or 70% (v/v) human serum. The antichlamydial activity of HMR 3647 was generally greater than that of commonly used antichlamydial antimicrobials. (+info)
Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future myocardial infarction.
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BACKGROUND: Chlamydia pneumoniae has been hypothesized to play a role in atherothrombosis. However, prospective data relating exposure to Chlamydia pneumoniae and risks of future myocardial infarction (MI) are sparse. METHODS AND RESULTS: In a prospective cohort of nearly 15 000 healthy men, we measured IgG antibodies directed against Chlamydia pneumoniae in blood samples collected at baseline from 343 study participants who subsequently reported a first MI and from an equal number of age- and smoking-matched control subjects who did not report vascular disease during a 12-year follow-up period. The proportion of study subjects with IgG antibodies directed against Chlamydia increased with age and cigarette consumption. However, prevalence rates of Chlamydia IgG seropositivity were virtually identical at baseline among men who subsequently reported first MI compared with age- and smoking-matched control subjects. Specifically, the relative risks of future MI associated with Chlamydia pneumoniae IgG titers >/=1:16, 1:32, 1:64, 1:128, and 1:256 were 1.1, 1.0, 1.1, 1.0, and 0.8, respectively (all probability values not significant). There was no association in analyses adjusted for other risk factors, evaluating early as compared with late events, or among nonsmokers. Further, there was no association between seropositivity and concentration of C-reactive protein, a marker of inflammation that predicts MI risk in this cohort. CONCLUSIONS: In a large-scale study of socioeconomically homogeneous men that controlled for age, smoking, and other cardiovascular risk factors, we found no evidence of association between Chlamydia pneumoniae IgG seropositivity and risks of future MI. (+info)
Role of innate and adaptive immunity in the outcome of primary infection with Chlamydia pneumoniae, as analyzed in genetically modified mice.
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Infection with Chlamydia pneumoniae is a common cause of acute respiratory disease in man and is also associated with atherosclerotic cardiovascular disorder. Herein, we have compared bacterial load and immune parameters of C. pneumoniae-infected mice genomically lacking T cell coreceptors, cytokine receptors, or cytotoxic effector molecules. A protective role for CD8+ cells is shown by the enhanced severity of infection of CD8-/- or TAP-1-/-/beta2-microglobulin -/- mice. CD8+ cells hindered a parasite growth-promoting role of CD4+ T cells, as indicated by the higher sensitivity to early infection of CD8-/- than CD4-/-/CD8-/- mice, which was further confirmed in experiments in which SCID mice were reconstituted with either CD4+ or CD4+ plus CD8+ T cells. Interestingly, CD4+ T cells played a dual role, detrimental early (14 and 24 days) after infection but protective at later time points (60 days after infection). The CD8+ T cell protection was perforin independent. The early deleterious role of CD4+ in the absence of CD8+ T cells was associated with enhanced IL-4 and IL-10 mRNA levels and delayed IFN-gamma mRNA accumulation in lungs. In line with this, IFN-gammaR-/- (but not TNFRp55 -/-) mice showed dramatically increased susceptibility to C. pneumoniae, linked to reduced inducible nitric oxide synthase (iNOS) mRNA accumulation, but not to diminished levels of specific Abs. The increased susceptibility of iNOS-/- mice indicates a protective role for iNOS activity during infection with C. pneumoniae. The higher sensitivity of IFN-gammaR-/- mice to C. pneumoniae compared with that of SCID or recombination-activating gene-1-/- mice suggested a relevant protective role of IFN-gamma-dependent innate mechanisms of protection. (+info)