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Background: Children with persistent Chlamydia pneumoniae infection may be at increased risk for atherosclerosis. The impact of antimicrobial therapy for primary prevention of atherosclerotic cardiovascular disease is unsolved., Objective: The purpose of this study was to determine whether treatment with antimicrobial agents effective against C pneumoniae during childhood, regardless of indication, has a favorable influence on the arterial wall-thickness in children by the time they reach adolescence., Subjects and Methods: The association of macrolide, tetracycline, quinolone, and rifamycin use (number of exposure events) between ages 5 and 13 years with carotid and aortic intima-media thickness at age 13 years was investigated among 508 healthy children. Information about the use of medications was obtained from the Finnish prescription register. Arterial intima-media thickness was measured with a high-resolution ultrasound., Results: Mean aortic intima-media thickness showed a significant direct association with the number of antichlamydial antimicrobial exposure events also after controlling for established atherosclerotic risk factors. Elevated C-reactive protein level had an additional effect on aortic intima-media thickness in a multivariable model. Carotid intima-media thickness was not associated with the number of preceding antichlamydial treatments., Conclusions: Recurrent antichlamydial treatments in childhood have no favorable influence on early vascular changes but are associated with increased intima-media thickness in the abdominal aorta. These findings suggest that the use of antimicrobial agents does not offer protection against the potential atherogenicity of repeated infectious insults.

Objective: The relationship between Chlamydia pneumoniae (Cpn) infection and arterial measures of preclinical atherosclerosis has remained controversial. Because atherogenesis begins in early life, we examined whether carotid and aortic intima-media thickness (IMT) and brachial artery endothelial function are associated with Cpn seropositivity in children., Methods and Results: Cpn-specific IgG and IgA antibodies were assessed by enzyme immunoassay in 199 healthy children followed-up annually from 7 to 11 years of age. Carotid (cIMT) and aortic IMT (aIMT), and brachial artery flow-mediated dilatation (FMD) were measured in 137 of the 199 children at the age of 11 years using high-resolution ultrasound. Children with persistent IgG and/or IgA seropositivity to Cpn had significantly increased aIMT compared with seronegative children (IgG< or =45 and IgA< or =12 enzyme immunounits) or children with transient Cpn seropositivity (seronegative, 0.496 [0.054]; transient, 0.494 [0.061]; and persistent, 0.532 [0.086] mm; P<0.05 for trend). This trend was not explained by traditional atherosclerotic risk factors or pubertal stage. cIMT and FMD were not associated with Cpn seropositivity., Conclusions: Eleven-year-old children with persistent Cpn seropositivity show increased aIMT but not cIMT, suggesting that Cpn may affect the aortic wall, the site where the earliest atherosclerotic lesions are known to occur, in otherwise healthy children.

Objective: Chronic Chlamydia pneumoniae (Cpn), Helicobacter pylori (Hp), and herpes virus infections have been associated with atherogenic serum lipid profile and an excess of cardiovascular events in adults. Because mechanisms leading to atherosclerosis are active since early childhood, we examined whether Cpn, Hp, or cytomegalovirus (CMV) seropositivity relates to serum lipid, lipoprotein, or apolipoprotein concentrations in children. We also looked for factors increasing probability of Cpn seropositivity in children., Methods and Results: Cpn-specific IgG and IgA, as well as Hp-specific and CMV-specific IgG antibodies were assessed by enzyme immunoassay in 199 apparently healthy children, followed-up from 7 to 11 years of age. Serum lipid profiles were studied at the ages of 7, 9, and 11 years using standard methods. Neither seroconversion to Cpn IgG or IgA antibody positivity nor persistent seropositivity for Cpn, Hp, or CMV was associated with proatherogenic serum lipid values. Children with siblings were more likely to possess Cpn antibodies than children without siblings (IgG: OR, 5.24; 95% CI, 1.63 to 16.82; IgA: OR, 3.32; 95% CI, 1.15 to 9.57)., Conclusions: These data suggest that contrary to the observations in adults, Cpn, Hp, and CMV seropositivity in otherwise healthy children is not associated with disturbances in serum lipid profile.

To provide insight into the appearance and longitudinal course of Chlamydia pneumoniae antibodies in childhood, C. pneumoniae immunoglobulin G (IgG), IgA and, in selected children, IgM antibodies were measured annually in 199 healthy children, followed prospectively from age 7 months to age 8 y (number of samples 1225) using a commercial enzyme immunoassay kit. IgG antibodies to C. pneumoniae were common throughout the follow-up, and the values declined rapidly after apparent infections during early childhood. Of the 128 identified seroconversions, 94 were probably primary infections and 34 reinfections. IgM antibodies were detected in 28% of the samples that showed a clear increase in IgG. IgA antibodies were scarce before 2 y of age, but their proportion then increased gradually. At the ages of 7 and 8 y, 10% of the children had clearly positive IgG and IgA antibody values. Increases in IgG were not associated with clinical respiratory symptoms. This study shows that C. pneumoniae infections probably occur commonly already at an early age, and that the infections are often asymptomatic. Consecutive high IgG and IgA antibody concentrations at the ages of 7 and 8 y indicate that persistent seropositivity for both antibodies may already develop in young children.

Background: Chlamydia pneumoniae infection has been associated with atherosclerosis by sero-epidemiological, histopathological and interventional studies, and animal experiments. We hypothesized that if chlamydial infection is causative of atherosclerosis, the occurrence of antibodies against C. pneumoniae should be associated with coronary vasomotor dysfunction - an early sign of atherosclerosis., Aim: To study the association between C. pneumoniae infection and coronary vasomotor function in young men without signs of ischemic heart disease., Methods: Serum IgG and IgA antibody concentrations against C. pneumoniae were determined in 125 clinically healthy subjects undergoing positron emission tomography (PET) studies. Myocardial blood flow was measured at rest and during pharmacologically induced hyperemia using [15O]H2O Coronary flow reserve was calculated as the ratio of hyperemic blood flow to resting blood flow., Results: No association was found between serum C. pneumoniae antibody concentrations and myocardial blood flow parameters. In contrast, more conventional risk factors for coronary artery disease, such as total cholesterol and apolipoprotein B, were inversely associated with hyperemic flow and flow reserve., Conclusions: We found no association between C. pneumoniae antibodies and coronary vasomotor function in subjects without ischemic heart disease. Thus, these results do not support the role of C. pneumoniae infection as an early phase risk factor for coronary artery disease.

Enzyme immunoassays (EIAs) for the detection of secretory IgA antibody (sIgA) to Chlamydia pneumoniae and Mycoplasma pneumoniae from saliva are described. The presence of salivary sIgA in healthy laboratory personnel (mean age 40, range 25-62 years) was detected using conjugates of antibodies directed against secretory and alpha-chain domains. The EIA results for the detection of C pneumoniae sIgA antibodies were confirmed by a sensitive microimmunofluorescence method used as a reference. Circulating IgA antibody levels in sera were also determined using commercial EIAs. Secretory IgA antibodies to both C pneumoniae and M. pneumoniae were detectable only from persons with positive or borderline circulating IgA antibodies. Moreover, C. pneumoniae sIgA was found in the saliva of a clinically healthy person whose serum IgA antibody levels had been constantly elevated during the past 7 years. In conclusion, because of their specificity the described methods could be used in further delineation of the role of anti-C pneumoniae and M. pneumoniae sIgA antibodies. However, owing to the unexpected high frequency of these antibodies in saliva of clinically healthy persons, it seems unlikely that a single sIgA measurement from saliva is diagnostically more powerful than a single IgA measurement from serum to study and interpret the involvement of these pathogens in chronic respiratory diseases.