Judy Gnarpe

Chlamydia pneumoniae but Not Cytomegalovirus Antibodies Are Associated With Future Risk of Stroke and Cardiovascular Disease A Prospective Study in Middle-Aged to Elderly Men With Treated Hypertension

BACKGROUND AND PURPOSE Several cross-sectional and prospective studies have indicated that high titers of antibodies to Chlamydia pneumoniae and cytomegalovirus (CMV) are associated with coronary heart disease. The aim of the present study was to examine whether elevated titers of antibodies to these pathogens are predictive of not only coronary but also cerebrovascular disease. METHODS Serum titers of antibodies to C pneumoniae (IgM, IgG, IgA, IgG immune complex) and CMV (IgG) were determined at baseline (n=130) and after 3.5 years (n=111) in a total sample of 152 men. All individuals had treated hypertension and at least 1 additional risk factor for cardiovascular disease (hypercholesterolemia, smoking, or diabetes mellitus) and constituted 93% of a randomly selected subgroup (n=164) of patients participating in a multiple risk factor intervention study. RESULTS Elevations of any or both of the IgA or IgG titers to C pneumoniae at entry or after 3.5 years were found in 84 cases (55%). Of those with high titers at entry, 97% remained high at the 3.5 year reexamination. After 6.5 years of follow-up, high titers to C pneumoniae at entry were associated with an increased risk for future stroke (relative risk [RR], 8.58; P=0.043; 95% CI, 1.07 to 68.82) and for any cardiovascular event (RR, 2.69; P=0.042; 95% CI, 1.04 to 6.97). A high serum titer of antibodies to CMV was found in 125 cases (85%), and this was not associated with an increased risk of future cardiovascular events. CONCLUSIONS Seropositivity for C pneumoniae, but not for CMV, was associated with an increased risk for future cardiovascular disease and, in particular, stroke.

A Randomized, Controlled Trial of Doxycycline and Rifampin for Patients with Alzheimer's Disease

Objectives: To assess whether doxycycline and rifampin have a therapeutic role in patients with Alzheimers disease (AD).

Multiple infections and subsequent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) study

Background—Limited prospective epidemiological data are available on the relation between exposure to Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), and hepatitis A virus (HAV), individually or as a total pathogen score, and human cardiovascular (CV) disease. Methods and Results—We analyzed enrollment sera from 3168 Canadian patients in the Heart Outcomes Prevention Evaluation (HOPE) study for antibodies to C pneumoniae, H pylori, CMV, and HAV and measured the relation between serostatus and 494 adjudicated trial outcomes of myocardial infarction, stroke, or CV death over 4.5 years of follow-up. CV events were associated with CMV serostatus (covariate-adjusted hazard ratio [HR], 1.24; 95% CI, 1.01, 1.53). Neither C pneumoniae IgG (adjusted HR, 0.87; 95% CI, 0.68, 1.10), C pneumonia IgA (adjusted HR, 1.10; 95% CI, 0.90, 1.34), H pylori IgG (HR, 0.99; 95% CI, 0.82, 1.19), nor HAV IgG (HR, 1.01; 95% CI, 0.83, 1.24) predicted CV events. Total pathogen score was associated with CV events (adjusted HR for 4 versus 1 or 0=1.41; 95% CI, 1.02, 1.96). Conclusions—Exposure to CMV but not to C pneumoniae, H pylori, or HAV was associated with a slight excess risk of subsequent myocardial infarction, stroke, or CV death in HOPE study patients, and total pathogen score based on these infections predicted a small increased hazard of CV events.

Chlamydia Pneumoniae (TWAR): a common agent in acute bronchitis

Patients seeking medical attention for respiratory infections were investigated with serology and culture for Chlamydia pneumoniae to investigate the prevalence of C. pneumoniae in a specific geographical area and its association with respiratory disease. Evidence for C. pneumoniae infection was found in approximately 25% of cases. 71% of patients with C. pneumoniae had symptoms from the lower respiratory tract as compared to 29% of the others. We conclude that C. pneumoniae can be a major cause of acute bronchitis.

Endemic Prevalence of Chlamydia pneumoniae in Subjectively Healthy Persons

Subjectively healthy persons were investigated for the presence of Chlamydia pneumoniae (TWAR) with throat cultures using the HL (human lung) cell line. C. pneumoniae was isolated from 11/234 investigated persons.

Bordetella pertussis, Bordetella parapertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae and Persistent Cough in Children

Material collected during a prospective pertussis vaccine trial in 1992-95 was examined for Bordetella pertussis (culture and serology), Bordetella parapertussis (culture), Mycoplasma pneumoniae and Chlamydia pneumoniae (PCR). From 64% (99/155) of episodes with cough for less than 100 d, 115 aetiological agents were identified in one southern and one northern subset of DT-recipients. The most common single agent was B. pertussis, representing 56%(64/115), with a median cough period of 51 d, followed by M. pneumoniae 26%(30/115), 23 d, C. pneumoniae 17% (19/115), 26 d, and B. parapertussis 2% (2/115). For co-infections, the median duration of cough was about 60 d. Spasmodic cough for 21 d or more (clinical WHO criteria for pertussis) was present in 82% (41/50) of infections with B. pertussis as single agent, 38% (17/45) with B. parapertussis, 38% (5/13) with C. pneumoniae, 26% (5/19) with M. pneumoniae and 30%(17/56) in cases where no aetiology was found. In children with cough for more than 100 d (n = 78) using all vaccine arms, B. pertussis was responsible in 83% (65/78), in 21%(16/78) together with other agents. Acellular vaccines were more efficient against serious disease than whole cell vaccine. Antibiotic treatment was more common at the southern (34%) study site than at the northern one (12%). The findings indicate that diagnosis should rely on laboratory confirmation, both for rational treatment of an individual case and for monitoring outbreaks.

Chlamydia pneumoniae in children with acute respiratory tract infections

Children seeking medical attention for acute respiratory tract infections were investigated for evidence of Chlamydia pneumoniae infection. Blood samples were obtained from 367 children. Nasopharyngeal or throat swabs for PCR analysis (polymerase chain reaction) were taken from 360 children. Serology was found to be useful for diagnosis of infection only in children aged 5 y. Using PCR, a prevalence of 8 and 10% of C pneumoniae was found in male and female children aged < 2 y; 17 and 19%, respectively, in the age group 2‐4 y and 32 and 21%, respectively, in the age group 5–16 y. We conclude that Chlamydia pneumoniae is a common finding in young children with respiratory tract infections. Younger children were more often found to have a moderate disease, but may have been ill for a long period.

Prevalence of Mycoplasma pneumoniae in subjectively healthy individuals

Subjectively healthy persons were investigated for the presence of Mycoplasma pneumoniae in throat cultures. During a peak period of M. pneumoniae incidence, 13.5% of 758 healthy volunteers were found to harbour the bacterium in the throat. The investigation was continued, and during a subsequent period of 11 months, the incidence of M. pneumoniae isolated decreased to 4.6% of 499 volunteers. All new blood donor sera 1990-1991 (422 sera) were screened for the presence of antibodies to M. pneumoniae; it was found that there was a fluctuating but significant number of individuals with positive serology based on a single test occasion.

Relationship of Anti-60 kDa Heat Shock Protein and Anti-Cholesterol Antibodies to Cardiovascular Events

Background—Several recent studies have indicated an association between key inflammatory mediators and atherosclerotic diseases. We evaluated whether high levels of antibodies against heat shock proteins and cholesterol (ACHA) predicted cardiovascular (CV) events. Methods and Results—We used blood samples from the Heart Outcomes Prevention Evaluation (HOPE) study to conduct a nested case-control study of 386 cases with CV events and 386 age- and sex-matched HOPE study controls without events. We explored the relationship between anti-hsp antibodies, ACHA, and subsequent outcomes (incident myocardial infarction, stroke, or CV death) during a mean follow-up of 4.5 years using conditional logistic regression. High levels of anti-hsp65 antibodies (≥90th percentile) predicted CV events (OR, 2.1; 95% CI, 1.2 to 3.9, P =0.01). Anti-hsp60 antibodies did not predict any event type, whereas incident stroke developed significantly less frequently in patients with high ACHA levels. Anti-hsp antibodies and ACHA did not correlate with inflammatory (fibrinogen, C-reactive protein, interleukin-6, intracellular adhesion molecule-1) or infectious markers (C pneumoniae or cytomegalovirus antibodies). Anti-hsp65 antibodies (≥90th percentile) and fibrinogen (highest tertile) had a strong joint effect: patients with high concentrations of both had more CV events (OR, 5.5; 95% CI, 1.8 to 17.5, P =0.004) than patients with low levels of both. A similar joint effect (OR, 2.7; 95% CI, 1.3 to 5.7, P =0.01) was found for high levels of anti-hsp65 and presence of cytomegalovirus antibodies. Conclusions—Serum antibodies to hsp65 were associated with subsequent CV events in this study of high-risk patients, independent of conventional cardiovascular risk factors and other inflammatory markers.

Prevalence of Chlamydia pneumoniae in healthy children and in children with respiratory tract infections.

BACKGROUND Chlamydia pneumoniae causes respiratory tract infections in adults, but little is known about its significance for acute or persistent respiratory tract infections in children. METHODS We studied the prevalence of C. pneumoniae by polymerase chain reaction in children younger than the age of 11: 85 consecutive children with respiratory tract infections; and 93 children presumed to be healthy. Throat swabs for PCR analysis were taken from all children, and serology was done for 54 of the 85 sick children and from all but one of the presumed healthy children positive for C. pneumoniae by PCR. RESULTS PCR was positive in 38 (45%) of the sick children and in 5 (5.7%) of the healthy children. All but 2 of 19 sick children with serologic findings suggesting recent or ongoing infection with C. pneumoniae were positive by PCR. Most children positive for C. pneumoniae by PCR had upper respiratory tract infections. Four children had recurrent respiratory tract infections and otitis media with effusion treated by tubal insertion. CONCLUSION The findings suggest that C. pneumoniae is common among children with respiratory tract infections.