Association between C-reactive protein, anti-Chlamydia pneumoniae antibodies, and vascular function in healthy adults.

Abnormalities of vascular function occur in patients with risk factors for atherosclerosis before the development of obstructive disease. Our pilot data suggest that elevated serum markers of infection and/or inflammation are associated with functional abnormalities of the vasculature in subjects at otherwise low risk for atherosclerosis.

Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults : the Cardiovascular Health Study.

BACKGROUND: Whether serological evidence of prior infection with Chlamydia pneumoniae, herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) is associated with myocardial infarction (MI) and coronary heart disease (CHD) death remains a source of controversy. METHODS AND RESULTS: We conducted a nested case-control study among participants in the Cardiovascular Health Study, a cohort study of persons aged >/=65 years. Cases experienced an incident MI and CHD death (n=213). Control subjects were matched to cases by age, sex, clinic, year of enrollment, and month of blood draw (n=405). Serum was analyzed for IgG antibodies to C pneumoniae, HSV-1, and CMV. After adjustment for other risk factors, the risk of MI and CHD death was associated with the presence of IgG antibodies to HSV-1 (odds ratio [OR] 2.0, 95% CI 1.1 to 3.6) but was not associated with the presence of IgG antibodies to either C pneumoniae (OR 1.1, 95% CI 0.7 to 1.8) or CMV (OR 1.2, 95% CI 0.7 to 1.9). Although there was little association with low to moderate C pneumoniae antibody titers (

Association of Chlamydia pneumoniae immunoglobulin A seropositivity and risk of lung cancer.

Chlamydia pneumoniae is a common respiratory pathogen that has also been associated with risk for chronic diseases, including atherosclerotic cardiovascular disease. Two recent studies have reported an association between serological evidence of past infection with the organism and lung cancer. To further evaluate this association, we conducted a case-control study among a subgroup of white male smokers identified for a population-based case-control study of lung cancer in western Washington between 1993 and 1995. Serum specimens obtained at study enrollment from 143 cases and 147 controls were tested for C. pneumoniae IgG, IgM, and IgA antibodies. In multivariate analysis controlling for smoking variables and educational status, IgA antibody titer 216 was independently associated with risk of lung cancer among subjects <60 years of age [odds ratio (OR), 2.67; 95% confidence interval (CI), 1.21-5.89] but not among older subjects (OR, 0.69; 95% CI, 0.34-1.43). Among subjects <60 years of age, there was suggestive evidence of a stronger association among current smokers (OR 4.31; 95% CI, 1.36-13.68) than former smokers (OR 1.50; 95% CI, 0.48-4.75; P for interaction term, 0.26). Additional studies, including prospective serological evaluations, are needed to further assess the possible significance of this association.

Chlamydia pneumoniae and the risk of first ischemic stroke : The Northern Manhattan Stroke Study.

BACKGROUND AND PURPOSE: Serological evidence of infection with Chlamydia pneumoniae has been associated with cardiovascular disease in multiple epidemiological studies. The data on its association with ischemic stroke are limited. We sought to determine whether chronic C pneumoniae infection is associated with ischemic stroke in a multi-ethnic population. METHODS: The Northern Manhattan Stroke Study contains a population-based, case-control study component. Cases had first ischemic stroke and matched control subjects were derived through random digit dialing. Titers of IgG, IgA, and IgM antibodies specific for C pneumoniae were measured with the use of microimmunofluorescence, and titers >/=1:16 were considered positive. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjustment for medical, behavioral, and socioeconomic factors. RESULTS: Eighty-nine cases and 89 control subjects were selected. Mean age among cases was 68.5+/-12.8 years; 53% were women and 15% of the subjects were white, 28% were black, and 54% were Hispanic. Elevated C pneumoniae IgA titers were significantly associated with risk of ischemic stroke after adjusting for other stroke risk factors (adjusted OR 4. 51, 95% CI 1.44 to 14.06). IgG titers were less strongly associated with stroke risk (adjusted OR 2.59, 95% CI 0.87 to 7.75). The association of IgA with stroke risk was detected in both younger and older groups, in men and women, and in whites, blacks, and Hispanics. There was also a significant continuous increase in risk associated with the log-transformation of the titer for IgA (adjusted OR 1.32, 95% CI 1.05 to 1.66) but not IgG. CONCLUSIONS: Serological evidence of chronic infection with C pneumoniae is associated with risk of ischemic stroke in an urban, multi-ethnic population. IgA titers may be a better marker of this risk than are IgG titers. This association is independent of other vascular disease risk factors. Further prospective epidemiological studies of the effect of this infection on stroke risk are warranted.

Frequency of serological evidence of Bordetella infections and mixed infections with other respiratory pathogens in university students with cough illnesses.

Banked acute-phase and convalescent-phase serum samples from a previous study of respiratory illness in university students were examined for significant (>/=2-fold) increases in ELISA titers of IgA and IgG antibody to Bordetella pertussis filamentous hemagglutinin, pertactin, and fimbriae-2 and >/=4-fold titer increases to agglutinogens by agglutination. ELISA titers of antibody to pertussis toxin could not be determined because of technical problems. Chlamydia pneumoniae infections were diagnosed by culture or by a >/=4-fold increase in immunofluorescence assay titer or a single high titer (>/=512). Mycoplasma pneumoniae, influenza A and B, adenovirus, and respiratory syncytial virus infections were diagnosed by >/=4-fold increases in complement fixation titer or a single high titer (>/=64). There were 319 subjects with cough of >/=5 days' duration, and of these, 47 (15%) had significant increases in antibody to B. pertussis antigens; 26 (8%) had significant increases to fimbriae-2 or agglutinogens, indicative of B. pertussis infection, and 2 (1%) had evidence of non-B. pertussis bordetella infections. Seventeen (36%) had evidence of mixed infections or cross-reacting antibodies (influenza B infections, 5; adenovirus infections, 4; influenza A infections, 3; C. pneumoniae infections, 3; and M. pneumoniae infections, 2). Our findings suggest that bordetella infections are common in young adults with cough illnesses (incidence, 9%), and a surprising number of these are mixed infections with other respiratory pathogens.

Background and current knowledge of Chlamydia pneumoniae and atherosclerosis.

Attributes of Chlamydia pneumoniae of potential importance to a relationship with atherosclerosis are described. Among these are that C. pneumoniae is not new. It is unique. It is a pathogen with which everyone is infected, and it is difficult to treat. It causes immunopathology, myocarditis, and endocarditis and chronicity is a hallmark of Chlamydia infection. Current knowledge of the relation of C. pneumoniae and atherosclerosis comes from observational (e.g., seroepidemiology and tissue studies) and experimental studies. The limitations of the serologic studies of chronic infection are noted as is the conclusive demonstration of an association of C. pneumoniae and atherosclerosis by the repeated and frequent finding of the organism in atherosclerotic tissue. Experimental studies are needed to determine if the association is causal. Such studies should include animal models, basic mechanisms, and secondary prevention antibiotic treatment trials.

Chlamydia pneumoniae and atherosclerotic risk in populations: the role of seroepidemiology.

While seroepidemiologic studies first suggested a possible association of prior infection with Chlamydia pneumoniae and atherosclerotic risk, the contribution of seroepidemiologic studies of C. pneumoniae and atherosclerotic risk remains a source of controversy, in part because the reported findings appear inconsistent. In general, cross-sectional studies of C. pneumoniae and atherosclerotic risk suggest an association, but recent reports from several prospective studies failed to demonstrate associations between the presence of IgG antibodies to C. pneumoniae and incident myocardial infarction. Evidence from other paradigms-pathologic, animal experimental, and molecular studies-supports a possible etiologic role for C. pneumoniae in atherothrombotic disease, raising questions about the contribution of seroepidemiologic studies. This review summarizes the major findings from seroepidemiologic studies in the context of other research paradigms, explores alternative explanations for the inconsistent findings, and suggests a further role for seroepidemiologic studies of C. pneumoniae and atherothrombotic risk.

Chlamydia pneumoniae serology: interlaboratory variation in microimmunofluorescence assay results.

The lack of standardization in chlamydia serology has made interpretation of published data difficult. This study was initiated to determine the extent of interlaboratory variation of microimmunofluorescence (MIF) test results for the serodiagnosis of Chlamydia pneumoniae infections. Identical panels of 22 sera were sent to 14 laboratories in eight countries for the determination of IgG and IgM antibodies by MIF. Although there was extensive variation in the numeric titer values, the overall percentage agreement with the reference standard titers from the University of Washington was 80%. For results by serodiagnostic category, the best agreement was for four-fold rise in IgG titers, while the lowest agreement was for negative or low IgG titers. Agreement for IgM titers was 50%-95%. Four laboratories failed to discern false-positive IgM titers possibly because of the presence of rheumatoid factor. Further studies are underway to determine the source of interlaboratory variation for the MIF test.

Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma.

Chlamydia pneumoniae is commonly detected in atherosclerotic plaque but the frequency of detection in non-cardiovascular (CV) tissues has not been well determined. In this study, archival autopsy tissue specimens from both CV and non-CV sites from 38 patients were tested by polymerase chain reaction and immunocytochemistry to detect C. pneumoniae. In addition, 33 surgical granuloma biopsy specimens were also tested. C. pneumoniae was detected most frequently in coronary artery tissue (34%) but was also detected in specimens from lung (13%), liver (10%), spleen (5%), bone marrow (10%), and lymph node (8%). The organism was detected in 3 of 33 granuloma specimens. These findings suggest that C. pneumoniae demonstrates a tropism for CV tissues and is either not widely distributed to non-CV tissues or does not persist chronically in those tissues after initial infection.

Past use of erythromycin, tetracycline, or doxycycline is not associated with risk of first myocardial infarction.

A population-based case-control study of patients enrolled at Group Health Cooperative of Puget Sound was conducted to evaluate whether past use of antibiotics active against Chlamydia pneumoniae is associated with a decrease in the risk of first myocardial infarction (MI). Cases with incident fatal and nonfatal MI from mid-1986 through 1995 (n=1796) were compared with randomly sampled controls frequency-matched to cases for age, sex, and year (n=4882). Use of erythromycin, tetracycline, or doxycycline during the previous 5 years was not associated with an alteration in the risk of first MI. In an adjusted logistic regression model, the odds ratios and 95% confidence intervals for categories of cumulative duration of therapy with any of the three agents combined for 0, 1-14, 15-28, and >/=29 days were 1.0 (reference), 0.93 (0.81-1.07), 0.99 (0.81-1.20), and 1.03 (0.84-1.26), respectively. These results suggest little or no association between past use of erythromycin or tetracycline antibiotics and the risk of first MI among this population.

Azithromycin vs cefuroxime plus erythromycin for empirical treatment of community-acquired pneumonia in hospitalized patients: a prospective, randomized, multicenter trial.

OBJECTIVE: To compare the efficacy and safety of azithromycin dihydrate monotherapy with those of a combination of cefuroxime axetil plus erythromycin as empirical therapy for community-acquired pneumonia in hospitalized patients. METHODS: Patients were enrolled in a prospective, randomized, multicenter study. The standard therapy of cefuroxime plus erythromycin was consistent with the American Thoracic Society, Canadian Community-Acquired Pneumonia Consensus Group, and Infectious Disease Society of America consensus guidelines. The doses were intravenous azithromycin (500 mg once daily) followed by oral azithromycin (500 mg once daily), intravenous cefuroxime (750 mg every 8 hours), followed by oral cefuroxime axetil (500 mg twice daily), and erythromycin (500-1000 mg) intravenously or orally every 6 hours. Randomization was stratified by severity of illness and age. Patients who were immunosuppressed or residing in nursing homes were excluded. RESULTS: Data from 145 patients (67 received azithromycin and 78 received cefuroxime plus erythromycin) were evaluable. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 19% (28/145) and 13% (19/145), respectively. The atypical pathogens accounted for 33% (48/145) of the etiologic diagnoses; Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma pneumoniae were identified in 14% (20/ 145), 10% (15/145), and 9% (13/145), respectively. Clinical cure was achieved in 91% (61/67) of the patients in the azithromycin group and 91% (71/78) in the cefuroxime plus erythromycin group. Adverse events (intravenous catheter site reactions, gastrointestinal tract disturbances) were significantly more common in patients who received cefuroxime plus erythromycin (49% [30/78]) than in patients who received azithromycin (12% [8/67]) (P<.001). CONCLUSIONS: Treatment with azithromycin was as effective as cefuroxime plus erythromycin in the empirical management of community-acquired pneumonia in immunocompetent patients who were hospitalized. Azithromycin was well tolerated.

Safety and effect on anti-Chlamydia pneumoniae antibody titres of a 1 month course of daily azithromycin in adults with coronary artery disease.

A pilot study of azithromycin treatment following percutaneous coronary revascularization procedures was performed to assess safety and the effect of azithromycin treatment on anti-Chlamydia pneumoniae antibody titres. Patients were randomized to a 1 month course of azithromycin (total dose of 8.0 g) or placebo. Safety and compliance were assessed at 2 and 4 weeks and serological testing was performed on samples obtained at enrolment and at 6 months post-enrolment. Azithromycin was well tolerated at this dose. No effect of treatment on antibody titres was demonstrated. These results support further clinical trials to assess the effect of azithromycin treatment on cardiovascular disease outcomes.

Lack of association of restenosis following coronary angioplasty with elevated C-reactive protein levels or seropositivity to Chlamydia pneumoniae.

Seventy-five consecutive patients undergoing directional coronary atherectomy were evaluated by measuring anti-Chlamydia immunoglobulin G and anticytomegalovirus immunoglobulin G antibodies, and serum levels of C-reactive proteins (before atherectomy). The results showed that although both Chlamydia infection and elevated C-reactive protein levels are associated with coronary artery disease and coronary artery disease events, neither of these appears to play a role in the development of restenosis.