Maija Leinonen

OBJECTIVE: To investigate in the prospective Helsinki Heart Study, whether chronic Chlamydia pneumoniae infection, indicated by elevated antibody titers against the pathogen, chlamydial lipopolysaccharide-containing immune complexes, or both, is a risk factor for coronary heart disease. DESIGN AND SETTING: The Helsinki Heart Study was a randomized, double-blind, 5-year clinical trial to test the efficacy of gemfibrozil in reducing the risk for coronary heart disease. Participants were randomized to receive either gemfibrozil (2046 patients) or placebo (2035 patients). Fatal and nonfatal myocardial infarction and sudden cardiac death were the main study end points. Serum samples were collected at 3-month intervals from all patients. PATIENTS: One hundred forty cardiac events occurred during the follow-up period. Serum samples from 103 case patients obtained 3 to 6 months before a cardiac end point were matched with those from controls for time point, locality, and treatment. Samples were tested for markers of chronic chlamydial infection. MEASUREMENTS: Immunoglobulin A (IgA) and G (IgG) antibodies to C. pneumoniae were measured using the microimmunofluorescence method. Lipopolysaccharide-containing immune complexes were measured using two antigen-specific enzyme immunoassays, the lipopolysaccharide-capture and immunoglobulin M (IgM)-capture methods. MAIN RESULTS: Using a conditional logistic regression model, odds ratios for the development of coronary heart disease were 2.7 (95% CI, 1.1 to 6.5) for elevated IgA titers, 2.1 (CI, 1.1 to 3.9) for the presence of immune complexes, and 2.9 (CI, 1.5 to 5.4) for the presence of both factors. If we adjusted for other coronary heart disease risk factors such as age, hypertension, and smoking, the corresponding values would be 2.3 (CI, 0.9 to 6.2), 1.8 (CI, 0.9 to 3.6), and 2.6 (CI, 1.3 to 5.2), respectively. CONCLUSION: The results suggest that chronic C. pneumoniae infection may be a significant risk factor for the development of coronary heart disease.

Two hundred young adults with common colds were studied during a 10-month period. Virus culture, antigen detection, PCR, and serology with paired samples were used to identify the infection. Viral etiology was established for 138 of the 200 patients (69%). Rhinoviruses were detected in 105 patients, coronavirus OC43 or 229E infection was detected in 17, influenza A or B virus was detected in 12, and single infections with parainfluenza virus, respiratory syncytial virus, adenovirus, and enterovirus were found in 14 patients. Evidence for bacterial infection was found in seven patients. Four patients had a rise in antibodies against Chlamydia pneumoniae, one had a rise in antibodies against Haemophilus influenzae, one had a rise in antibodies against Streptococcus pneumoniae, and one had immunoglobulin M antibodies against Mycoplasma pneumoniae. The results show that although approximately 50% of episodes of the common cold were caused by rhinoviruses, the etiology can vary depending on the epidemiological situation with regard to circulating viruses. Bacterial infections were rare, supporting the concept that the common cold is almost exclusively a viral disease.

OBJECTIVES: The precise epidemiology of childhood pneumonia remains poorly defined. Accurate and prompt etiologic diagnosis is limited by inadequate clinical, radiologic, and laboratory diagnostic methods. The objective of this study was to determine as precisely as possible the epidemiology and morbidity of community-acquired pneumonia in hospitalized children. METHODS: Consecutive immunocompetent children hospitalized with radiographically confirmed lower respiratory infections (LRIs) were evaluated prospectively from January 1999 through March 2000. Positive blood or pleural fluid cultures or pneumolysin-based polymerase chain reaction assays, viral direct fluorescent antibody tests, or viral, mycoplasmal, or chlamydial serologic tests were considered indicative of infection by those organisms. Methods for diagnosis of pneumococcal pneumonia among study subjects were published by us previously. Selected clinical characteristics, indices of inflammation (white blood cell and differential counts and procalcitonin values), and clinical outcome measures (time to defervescence and duration of oxygen supplementation and hospitalization) were compared among groups of children. RESULTS: One hundred fifty-four hospitalized children with LRIs were enrolled. Median age was 33 months (range: 2 months to 17 years). A pathogen was identified in 79% of children. Typical respiratory bacteria were identified in 60% (of which 73% were Streptococcus pneumoniae), viruses in 45%, Mycoplasma pneumoniae in 14%, Chlamydia pneumoniae in 9%, and mixed bacterial/viral infections in 23%. Preschool-aged children had as many episodes of atypical bacterial LRIs as older children. Children with typical bacterial or mixed bacterial/viral infections had the greatest inflammation and disease severity. Multivariate logistic-regression analyses revealed that high temperature (> or = 38.4 degrees C) within 72 hours after admission (odds ratio: 2.2; 95% confidence interval: 1.4-3.5) and the presence of pleural effusion (odds ratio: 6.6; 95% confidence interval: 2.1-21.2) were significantly associated with bacterial pneumonia. CONCLUSIONS: This study used an expanded diagnostic armamentarium to define the broad spectrum of pathogens that cause pneumonia in hospitalized children. The data confirm the importance of S pneumoniae and the frequent occurrence of bacterial and viral coinfections in children with pneumonia. These findings will facilitate age-appropriate antibiotic selection and future evaluation of the clinical effectiveness of the pneumococcal conjugate vaccine as well as other candidate vaccines.

BACKGROUND: Childhood community-acquired pneumonia is a common illness, but there have been relatively few comprehensive studies of the viral and bacterial etiology in developed countries. The aim of the present investigation was to determine the etiology of community-acquired pneumonia in hospitalized children by several laboratory methods. METHODS: In a 3-year prospective study a nasopharyngeal aspirate for viral studies and acute and convalescent serum samples for viral and bacterial serology were taken from 254 children with symptoms of acute infection and infiltrates compatible with pneumonia in the chest radiograph. The role of 17 microbes was investigated. RESULTS: A potential causative agent was detected in 215 (85%) of the 254 patients. Sixty-two percent of the patients had viral infection, 53% had bacterial infection and 30% had evidence of concomitant viral-bacterial infection. Streptococcus pneumoniae (37%), respiratory syncytial virus (29%) and rhinovirus (24%) were the most common agents associated with community-acquired pneumonia. Only one patient had a positive blood culture (S. pneumoniae) of 125 cultured. A dual viral infection was detected in 35 patients, and a dual bacterial infection was detected in 19 patients. CONCLUSIONS: The possible causative agent of childhood community-acquired pneumonia can be detected in most cases. Further studies are warranted to determine what etiologic investigations would aid in the management of pneumonia. With effective immunization for S. pneumoniae and respiratory syncytial virus infections, more than one-half of the pneumonia cases in this study could have been prevented.