San Pin Wang

Chlamydia pneumoniae (TWAR) in atherosclerosis of the carotid artery.

BACKGROUNDnChlamydia pneumoniae has been demonstrated in atherosclerotic lesions of coronary arteries and aorta. A seroepidemiological study found C pneumoniae-specific antibody more frequently in persons with significant carotid artery wall thickening than in matched control subjects.nnnMETHODS AND RESULTSnFresh-frozen or formalin-fixed tissue obtained at carotid endarterectomy was examined by immunocytochemistry (ICC) and the polymerase chain reaction (PCR) for the presence of C pneumoniae. Five of five fresh-frozen and formalin-fixed carotid endarterectomy specimens were positive for C pneumoniae by ICC (three of five by PCR). A total of 56 archival formalin-fixed, paraffin-embedded carotid endarterectomy tissues from three hospitals were examined by ICC. Thirty-two were positive. Thirteen normal carotid artery tissue sections from six patients were negative for C pneumoniae.nnnCONCLUSIONSnC pneumoniae organisms are frequently found in the advanced carotid atherosclerotic lesions of persons undergoing endarterectomy. Although these findings do not establish causality for C pneumoniae in carotid artery atherosclerosis, they should stimulate investigation of a possible causal or pathogenic role for the organism in the disease.

Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis

PURPOSEnTo 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.nnnSUBJECTS AND METHODSnBetween 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.nnnRESULTSnSeventy-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.nnnCONCLUSIONnThere was a significant cross-sectional association between past TWAR infection and asymptomatic atherosclerosis. This organism may be a contributor to the pathogenesis of atherosclerosis.

Confirmed Previous Infection With Chlamydia pneumoniae (TWAR) and Its Presence in Early Coronary Atherosclerosis

BACKGROUNDnChlamydia pneumoniae has been identified in coronary atheroma, but concomitant serum antibody titers have been inconsistently positive and unavailable before the detection of early or advanced atherosclerotic lesions.nnnMETHODS AND RESULTSnThis retrospective investigation was performed on premortem serum specimens and autopsy tissue from 60 indigenous Alaska Natives at low risk for coronary heart disease, selected by the potential availability of their stored specimens. Serum specimens were drawn a mean of 8.8 years (range, 0.7 to 26.2 years) before death, which occurred at a mean age of 34.1 years (range, 15 to 57 years), primarily from noncardiovascular causes (97%). Coronary artery tissues were independently examined histologically and, for C pneumoniae organism and DNA, by immunocytochemistry (ICC) and polymerase chain reaction (PCR) with species-specific monoclonal antibody and primers. Microimmunofluorescence detected species-specific IgG, IgA, and IgM antibody in stored serum. C pneumoniae, frequently within macrophage foam cells, was identified in coronary fibrolipid atheroma (raised lesions, Stary types II through V) in 15 subjects (25%) and early flat lesions in 7 (11%) either by PCR (14, 23%) or ICC (20, 33%). The OR for C pneumoniae in raised atheroma after a level of IgG antibody > or =1:256 >8 years earlier was 6.1 (95% CI, 1.1 to 36.6) and for all coronary tissues after adjustment for multiple potential confounding variables, including tobacco exposure, was 9.4 (95% CI, 2.6 to 33.8).nnnCONCLUSIONSnSerological evidence for C pneumoniae infection frequently precedes both the earliest and more advanced lesions of coronary atherosclerosis that harbor this intracellular pathogen, suggesting a chronic infection and developmental role in coronary heart disease.

INCREASED FREQUENCY OF SERUM ANTIBODIES TO CHLAMYDIA TRACHOMATIS IN INFERTILITY DUE TO DISTAL TUBAL DISEASE

186 infertile women underwent standard infertility investigations (including hysterosalpingography and, in 87 women, laparoscopy) and tests for the presence of antibody to Chlamydia trachomatis. 73% of the women with distal occlusion of the fallopian tubes and 21% with peritubal adhesions alone had antibodies to C. trachomatis, but none of those with normal tubes did (p less than 0.001 and less than 0.005, respectively). No other infertility factors were associated with an increased frequency of antibodies to C. trachomatis. Since the presence or absence of antibodies to C. trachomatis was as discriminatory in the detection of tubal disease in infertile women as was the hysterosalpingogram, the serological test for C. trachomatis should become part of a routine infertility investigation.

Detection of Chlamydia trachomatis in fallopian tube tissue in women with postinfectious tubal infertility

OBJECTIVEnBiopsy tissues from women with postinfectious tubal infertility were studied for the presence of Chlamydia trachomatis.nnnSTUDY DESIGNnTubal biopsy specimens from 25 women with postinfectious tubal infertility undergoing laparoscopy for repair of fallopian tubes were evaluated by culture, in situ hybridization. Immunocytochemistry, and transmission electron microscopy for the presence of Chlamydia trachomatis. Serum was also tested for Chlamydia trachomatis antibodies.nnnRESULTSnChlamydia trachomatis was detected in postinfectious tubal biopsy specimens in three of 25 patients by culture, 12 of 24 by in situ hybridization, 15 of 22 by immunoperoxidase stain, and two of 10 by transmission electron microscopy. Serum antibody against Chlamydia trachomatis was detected in 15 of 21 patients.nnnCONCLUSIONnChlamydia trachomatis deoxyribonucleic acid or antigens were detected at a high percentage (19/24 women) in the biopsy tissues of the fimbrial and peritubal adhesions by in situ hybridization or immunoperoxidase stain, suggesting a persistent infection in these women even after antibiotic treatment.

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.

Chlamydia trachomatis infection in Fitz-Hugh-Curtis syndrome

We studied 23 patients with pelvic inflammatory disease associated with symptoms of pleuritic upper abdominal pain, characteristic of Fitz-Hugh-Curtis syndrome (FHC). A fourfold or greater change in antibody titer to Chlamydia trachomatis was demonstrated by microimmunofluorescence in 14; an IgG antibody titer greater than or equal to 1:1,024 was seen in 13; and IgM antibody was demonstrated in 11. Twenty (87%) of the 23 FHC patients, including all of the 12 with paired sera obtained at least 6 weeks apart, had serologic evidence of acute C. trachomatis infection. Neisseria gonorrhoeae was isolated from seven (30%) of the 23 FHC cases, and C. trachomatis was isolated from three of 10. Two groups of matched controls were studied; one group with PID but without FHC, and the other without PID. A larger proportion of patients with FHC had serologic evidence of acute C. trachomatis infection than either of the two control groups (p less than 0.05 for each comparison). Among those with antibody to C. trachomatis, the geometric mean antibody titer for the FHC group (1:724) was significantly higher than that for the PID group (1:138) or for the non-PID group (1:103). Thus, FHC is not solely attributable to infection with N. gonorrhoeae; most cases are associated with acute C. trachomatis infection.

Microbial causes of neonatal conjunctivitis

We assessed the microbial causes of neonatal conjunctivitis by comparing 55 infants with purulent conjunctivitis and 60 healthy control infants. A mean of >5 leukocytes per 1000× microscopic field was seen in Gram-stained smears obtained from the more inflamed eye in 77% of 30 untreated patients but none of 57 controls. Pathogens isolated more often from untreated patients than from controls included Haemophilus spp. (17% vs 2%, P=0.01). Staphylococcus aureus (17% vs 2%, P=0.01). Chlamydia trachomatis (14% vs 0%, P=0.01), enterococci (8% vs 0%, P=0.05), and Streptococcus pneumoniae (11% vs 2%, P=0.06). One or more of these pathogens were isolated from the conjunctivae in 58% of patients and 5% of controls (P

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.