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 (

Community- and hospital-acquired pneumonia associated with Chlamydia TWAR infection demonstrated serologically.

Serum specimens from 198 patients with pneumonia hospitalized in Seattle between October 1980 and April 1981 were retrospectively tested for antibody against a recently described Chlamydia organism called TWAR. They had been previously tested for antibody for some viruses and Mycoplasma. Twenty (10%) had serologic evidence of recent TWAR infection. The hospital records of the patients with acute TWAR antibody and an equal number of matched controls were examined for clinical characteristics, laboratory tests, treatment, and course during the hospital stay. It was not possible clinically or roentgenographically to distinguish pneumonia associated with TWAR antibody from pneumonia in the controls. Nine of 20 patients with TWAR antibody acquired pneumonia during their hospital stay. The mode of transmission in the hospital was not determined. All the patients with hospital-acquired pneumonia had been intubated, and all had had some surgical procedure. Ten of 20 control patients had onset of their pneumonia in the hospital. Fifteen (11%) of 142 of the patients with pneumonia had evidence of influenza A virus infection. The clinical characteristics of their pneumonias were similar to those of the patients with acute TWAR antibody.

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.

New and emerging etiologies for community-acquired pneumonia with implications for therapy. A prospective multicenter study of 359 cases.

Three hundred fifty-nine consecutive patients with community-acquired pneumonia admitted to university, community, and VA hospitals underwent a standardized evaluation, including specialized tests for Legionella spp. and Chlamydia pneumoniae (TWAR). The most common underlying illnesses were immunosuppression (36.3%), chronic obstructive pulmonary disease (32.4%), and malignancy (28.4%). The most frequent etiologic agents were Streptococcus pneumoniae (15.3%) and Hemophilus influenzae (10.9%). Surprisingly, Legionella spp. and C. pneumoniae were the third and fourth most frequent etiologies at 6.7% and 6.1%, respectively. Aerobic gram-negative pneumonias were relatively uncommon causes of pneumonia despite the fact that empiric broad-spectrum combination antibiotic therapy is so often directed at this subgroup. In 32.9%, the etiology was undetermined. Antibiotic administration before admission was significantly associated with undetermined etiology (p = 0.0003). There were no distinctive clinical features found to be diagnostic for any etiologic agent, although high fever occurred more frequently in Legionnaires' disease. Clinical manifestations for C. pneumoniae were generally mild, although 38% of patients had mental status changes. Mortality was highest for Staphylococcus aureus (50%) and lowest for C. pneumoniae (4.5%) and Mycoplasma pneumoniae (0%). We document that specialized laboratory testing for C. pneumoniae and Legionella spp. should be more widely used rather than reserved for cases not responding to standard therapy. Furthermore, realization that C. pneumoniae and Legionella spp. are common etiologies for community-acquired pneumonia should affect empiric antibiotic prescription.

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.

Ofloxacin treatment of Chlamydia pneumoniae (strain TWAR) lower respiratory tract infections.

PURPOSE: Limited data suggest that tetracycline or erythromycin is the antibiotic of choice for treating Chlamydia pneumoniae infection, but they are not always effective or well tolerated. Because the fluoroquinolone ofloxacin is effective for Chlamydia trachomatis infections, we investigated its role in treating C. pneumoniae infections. PATIENTS AND METHODS: Eighty-seven patients were enrolled in a randomized trial of antibiotic therapy for acute lower respiratory tract infections. The patients were randomly assigned to oral treatment with either ofloxacin (400 mg twice a day) or erythromycin (400 mg four times a day) for 10 days. Frozen acute and convalescent serologic specimens were tested for TWAR antibody by microimmunofluorescence. Susceptibility testing of C. pneumoniae to ofloxacin was also performed. RESULTS: Four patients who received ofloxacin were retrospectively identified as having C. pneumoniae pneumonia (two) or bronchitis (two). Within 2 weeks of starting ofloxacin therapy, all were cured or markedly improved. The minimum inhibitory concentrations of ofloxacin for three previously isolated clinical strains of C. pneumoniae were determined to be 1.0 to 2.0 micrograms/mL, well within the achievable serum levels (3 to 5 micrograms/mL) with ofloxacin therapy. CONCLUSION: Ofloxacin may be an effective alternative antibiotic treatment for C. pneumoniae respiratory infections.

Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

PURPOSE: To determine whether past infection by Chlamydia pneumoniae strain TWAR is associated with asymptomatic atherosclerosis. Previous studies have linked this organism with symptomatic coronary heart disease. SUBJECTS AND METHODS: Between 1986 and 1989, 15,800 men and women aged 45 to 64 years were examined as part of the Atherosclerosis Risk in Communities Study, a prospective cohort study of atherosclerosis being conducted in 4 United States communities. The examination included B-mode ultrasonography of the carotid arteries and an assessment of cardiovascular disease risk factors. Carotid wall thickening (blood-intima to medial-adventitial interface) in the absence of clinical cardiovascular disease was considered evidence of asymptomatic atherosclerosis. In 1991, IgG antibody titers to TWAR were assayed by microimmunofluorescence in stored sera from 326 case-control pairs matched by age group, race, sex, examination period, and field center. A titer of 1:8 or higher was considered a positive TWAR antibody response. RESULTS: Seventy-three percent of atherosclerosis cases had serologic evidence of past TWAR infection versus 63% of controls (matched odds ratio 1.76; 95% confidence interval, 1.21 to 2.57). After adjustment for age, hypertension, diabetes, cigarette smoking, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and education, the odds ratio for atherosclerosis was essentially unchanged at 2.00 (95% confidence interval, 1.19 to 3.35). The association was stronger for individuals aged 45 to 54 years than for those aged 55 to 64 years. CONCLUSION: There was a significant cross-sectional association between past TWAR infection and asymptomatic atherosclerosis. This organism may be a contributor to the pathogenesis of atherosclerosis.

Randomized trial of silver nitrate, erythromycin, and no eye prophylaxis for the prevention of conjunctivitis among newborns not at risk for gonococcal ophthalmitis. Eye Prophylaxis Study Group.

OBJECTIVE: To compare the efficacy of commonly used forms of eye prophylaxis for newborns with no prophylaxis in the prevention of nongonococcal conjunctivitis. DESIGN: Randomized doubly masked clinical trial. SETTING: University of Washington Hospital and affiliated clinics, Seattle, between 1985 and 1990. SUBJECTS: The medical records of 8499 women were evaluated for possible participation; 2577 were eligible. Of the 758 enrolled, the infants of 630 were evaluable. INTERVENTION: Comparison of silver nitrate, erythromycin, and no eye prophylaxis given at birth for the prevention of conjunctivitis. MAIN OUTCOME MEASURES: Conjunctivitis during the first 60 days of life and nasolacrimal duct patency in the first 2 days of life. RESULTS: The frequency of impatent tear ducts at the 30- to 48-hour examination did not differ significantly by prophylaxis group. Among the 630 infants randomized and observed, 109 (17%) developed mild conjunctivitis. Sixty-nine (63%) of the cases appeared during the first 2 weeks of life. After 2 months of observation, infants allocated to silver nitrate eye prophylaxis at birth had a 39% lower rate of conjunctivitis (hazard ratio = 0.61, 95% confidence interval = 0.39 to 0.97), and those allocated to erythromycin had a 31% lower rate of conjunctivitis (hazard ratio = 0.69, 95% confidence interval = 0.44 to 1.07), than did those allocated to no prophylaxis. CONCLUSION: Silver nitrate eye prophylaxis caused no sustained deleterious effects and even provided some benefit to infants born to women without Neisseria gonorrhoeae. However, the effect was modest and against microorganisms of low virulence. The results suggest that parental choice of a prophylaxis agent including no prophylaxis is reasonable for women receiving prenatal care and who are screened for sexually transmitted diseases during pregnancy.

Direct fluorescent monoclonal antibody stain for rapid detection of infant Chlamydia trachomatis infections.

A method of direct fluorescent antibody staining for rapid diagnosis of Chlamydia trachomatis infections in infants is described. This method utilized a fluorescein-conjugated species-specific monoclonal antibody to C trachomatis for detecting chlamydial elementary bodies in smears of the conjunctiva, nasopharynx, oropharynx, anus, and vagina. The sensitivity of direct fluorescent antibody staining was compared with isolation of the organisms in McCoy cells. Thirty-nine infants with purulent conjunctivitis were studied. Diagnosis of C trachomatis conjunctivitis was correctly made by smear in all 16 infants when inflamed eyes were sampled. Positive smears were obtained from 12/14 culture-positive and 4/16 culture-negative nasopharyngeal specimens from infants with chlamydial conjunctivitis. All nasopharyngeal cultures and smears from infants with nonchlamydial conjunctivitis were negative. These results indicate that the direct smear test is a sensitive and specific test for diagnosing C trachomatis infection of the eye and nasopharynx in infants, and this test can be completed within one hour of specimen collection.

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.

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.

Delayed appearance of Chlamydia trachomatis infections acquired at birth.

To determine the delay in detectability of Chlamydia trachomatis infections acquired at birth, we serially evaluated 120 infants born vaginally to infected women. Specimens for isolation of Chlamydia were taken from several anatomic sites. Results were analyzed for the age and site of the initial positive culture from each infant. Of 112 infants tested in the first month of life, 22% were culture-positive in the conjunctiva and 25% were positive in the pharynx. Initial positive rectal and vaginal cultures were obtained only in the third and fourth months of life, and all initial vaginal cultures were associated with positive rectal cultures. The latency of C. trachomatis in infants exposed at birth is often more than 1 month and can be longer than 97 days. This latency might be caused by suppression of the growth of the organism by antibodies acquired in utero.

Vaginal douching as a risk factor for acute pelvic inflammatory disease.

OBJECTIVE: To conduct a population-based evaluation of vaginal douching as a risk factor for acute pelvic inflammatory disease (PID), emphasizing timing, frequency, and reasons for douching. METHODS: A population-based case-control study was conducted at Group Health Cooperative of Puget Sound, a staff-model health maintenance organization located in western Washington state. The cases (N = 131) were women 18-40 years of age who experienced a first episode of clinically diagnosed acute PID. Both hospitalized and ambulatory-care patients were identified. Medical records were reviewed for clinical inclusion criteria and for additional evidence of inflammation/infection. Controls (N = 294) were chosen from a population-based series of randomly selected women from a concurrent Group Health study of ectopic pregnancy. Of the women identified, 72.4% of cases and 73.4% of controls agreed to participate. RESULTS: Relative to women who reported never having douched, women who douched during the previous 3 months had a risk of PID of 2.1 after controlling for other measured risk factors (95% confidence interval [CI] 1.2-3.9). Women who douched at least once a week had a higher estimated risk (odds ratio 3.9, 95% CI 1.4-10.9) than those who douched less often (odds ratio 1.8, 95% CI 1.0-3.4). The risk was highest in the small group of women who gave infection as the reason for douching (odds ratio 7.9, 95% CI 2.6-24.2). However, exclusion of this group did not eliminate the association among the remaining women (odds ratio 3.0, 95% CI 1.0-9.1 for douching at least once a week). CONCLUSION: These population-based data lend added support to the hypothesis that vaginal douching can predispose a woman to PID.

Serologic evidence of respiratory and rickettsial infections among Somali refugees.

Somali refugees living in a camp located in Djibouti were studied in October 1991 and May 1992. The refugees had been living at the camp for about two years. The median age of volunteers was 25 years, of whom 69% were female. Paired sera obtained seven months apart were evaluated by complement fixation, microimmunofluorescence, indirect fluorescent antibody, streptococcal antibody, and enzyme-linked immunosorbent assay techniques for evidence of pathogen infection. Fifty-two percent, 31.3%, 8.0%, 5.9%, and 25.4% of the volunteers had serologic evidence for pre-enrollment infection with Chlamydia pneumoniae, Mycoplasma pneumoniae, Rickettsia typhi, R. conorii, and Coxiella burnetti, respectively. Similarly, 43.5%, 5.2%, 6.1%, 10.7%, 15.8%, and 11.9% of the volunteers studied had serologic evidence for new infection with Streptococcus pyogenes, C. pneumoniae, M. pneumoniae, R. typhi, R. conorii, and Cox. burnetii, respectively. These data suggest that the studied pathogens may be endemic in displaced populations living in the Horn of Africa.

The association between Chlamydia trachomatis serology and pelvic damage in women with tubal ectopic gestations.

OBJECTIVE: To determine whether pelvic damage is associated with positive Chlamydia trachomatis serology in women with tubal ectopic pregnancy. DESIGN: Cross-sectional retrospective study. SETTING: A prepaid health maintenance organization. PATIENTS: Two-hundred eighty-one women admitted with confirmed tubal ectopic pregnancy were interviewed for history of sexually transmitted diseases. Chlamydia serology was obtained for 135 subjects, and operative findings were available for 121 of these. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Pelvic damage, as determined by review of operative findings of the pelvis at the time of ectopic surgery. RESULTS: Pelvic damage was associated with positive chlamydia serology with an adjusted odds ratio of 4.2 (95% confidence interval: 1.8 to 9.7). Moderate and severe pelvic damage were more strongly associated with positive serology than mild damage. CONCLUSIONS: Women with ectopic pregnancies and antibodies to C. trachomatis are more likely to have damaged pelves than women with ectopic pregnancies without such antibodies. Prevention or early treatment of C. trachomatis infection may reduce pelvic damage and, therefore, reduce incidence of ectopic pregnancy.

Long term follow-up study of a trachoma vaccine trial in villages of Northern India.

A field trial of two high titer bivalent trachoma vaccines was done in a rural area of Northern India in children under the age of 6 years. Three months later 310 of the original 451 children in the study received a booster vaccination of either of the two vaccines or a placebo. Both the sucrose gradient purified and the Genetron purified vaccine protected against trachoma infection for one year. Significant protection for two years was found only with the gradient vaccine. A 12-year follow-up study located and examined 201 subjects that had received booster vaccine. It was found that 31, 27, and 28% of the individuals in each of the three groups (two vaccine and placebo) had evidence of mostly minimally active trachoma. Additionally, from 6 to 10% of the subjects in each group had signs of mild to moderate potentially blinding sequelae. The results showed no protection by either vaccine, and there was no evidence of adverse effects from the vaccines.

Infections with Chlamydia pneumoniae strain TWAR.

Chlamydia pneumoniae has recently been recognized as an important cause of respiratory tract disease, including atypical pneumonia. Serosurveys suggest that C. pneumoniae is endemic in most countries and is capable of causing outbreaks and epidemics of pneumonia, especially in countries where the antibody prevalence is relatively low. The population incidence of infection appears to be cyclical, with approximately 4-year cycles in the US (Seattle) and 6-year cycles in Denmark having been demonstrated. Pneumonia caused by the organism is unusual in young children in developed countries but may be an important cause of lower respiratory infections among children in developing and tropical countries. In otherwise healthy adults, C. pneumoniae pneumonia usually can be treated effectively on an outpatient basis. Patients with C. pneumoniae pneumonia often have a gradual onset of symptoms: a sore throat and hoarseness followed by a cough. Auscultatory and radiographic findings usually are prominent, even in patients with mild disease, and a cough and malaise may persist for several weeks or more after appropriate therapy. Microimmunofluorescence serologic testing is available in only a few laboratories. However, the new HL cell line holds promise of making culture and isolation of C. pneumoniae more widely available. Questions remain about the routes of transmission of C. pneumoniae, its incubation period, its role in lower respiratory disease in children in developing countries, the optimal antibiotic therapy, the existence and importance of chronic and latent C. pneumoniae infections, and the organism's association with nonrespiratory tract disease.

Experimental infection of baboons (Papio cynocephalus anubis) with Chlamydia pneumoniae strain 'TWAR'.

Two infant baboons (Papio cynocephalus anubis) were inoculated with Chlamydia pneumoniae strain 'TWAR', one in the conjunctiva, nasopharynx and oropharynx, the other in the trachea. Both remained well during 8 weeks of observation. C. pneumoniae infection persisted for at least 8 weeks after inoculation. Chlamydia pneumoniae seems to be of low virulence in baboons and capable of causing chronic infection.

Risk of perinatal transmission of Chlamydia trachomatis by mode of delivery.

We compared the transmission rate of Chlamydia trachomatis infection from infected women to their infants after various modes of delivery. After vaginal birth, Chlamydia trachomatis was isolated from 58 of 125 infants with a cephalic presentation, and serological evidence of chlamydial infection was found in another eight. C. trachomatis was isolated from the only infant with a frank breech presentation. After Caesarean birth, C. trachomatis was isolated from two of 10 infants born after rupture of the membranes and from one of six without prior rupture of the membranes. No serological evidence of infection was found in any of the culture-negative infants born by Caesarean section. By survival analysis, rates of transmission were significantly lower after Caesarean section with rupture of the membranes before delivery than after vaginal delivery. Infants born to infected women are at risk of C. trachomatis infection regardless of route of delivery.

Prevalence of positive serology for acute Chlamydia pneumoniae infection in emergency department patients with persistent cough.

OBJECTIVE: To determine the prevalence of acute Chlamydia pneumoniae infection in ED patients presenting with a persistent cough. METHODS: This was a case series consisting of a convenience sample of 65 patients > or = 18 years of age who presented with a chief complaint of a cough lasting > or = 2 weeks. Patients were treated in the ED of an urban university hospital. Patients with immunosuppression, lung disease, pneumonia, or a cough lasting > or = 3 months were excluded. Acute and convalescent sera were assayed for antibody to C. pneumoniae. Subjects with C. pneumoniae antibody titers showing a fourfold rise in either immunoglobin M (IgM) or immunoglobin G (IgG) antibody, an IgM titer of > or = 16, or an IgG titer of > or = 512 were considered to have evidence of acute C. pneumoniae infection. RESULTS: Thirteen (20%; 95% CI, 11% to 32%) of the 65 subjects had serologic evidence of acute C. pneumoniae infection. Except for an increased rate of fever, clinical signs and symptoms and laboratory studies did not differentiate those who had C. pneumoniae from those who did not have the disease. Patients diagnosed as having Bordetella pertussis or Mycoplasma pneumoniae infection did not have serologic evidence of concurrent C. pneumoniae infection. CONCLUSIONS: C. pneumoniae infection appears to be associated with a persistent cough in ED patients. Clinicians should consider this organism when evaluating these patients. It is unclear whether antibiotic therapy is indicated for these patients. If antibiotics are used, a tetracycline or macrolide antibiotic would be most appropriate.