Strain TWAR Research Articles

Selected aspects of Chlamydophila pneumoniae infections

Chlamydophila pneumoniae was taxonomically separated from strain TWAR - an abbreviation of the strain isolated from humans TW-183 (material from the eye of a child in Taiwan in 1965) and AR-39 (material from a student's throat swab with acute changes within airways in Seattle in 1983). The basis of separation of the C. pneumoniae species was the unique structure of the elementary bodies. Infection caused by C. pneumoniae is often asymptomatic (60-80% of all infections). Symptomatic infections of the upper respiratory tract relate to pharyngitis, laryngitis, sinusitis and the lower respiratory tract: bronchitis and pneumonia. C. pneumoniae infection often transforms into a chronic, clinically oligo- or asymptomatic form. The chronic inflammatory process is associated by many authors with the pathogenesis of coronary artery disease, endocarditis, atherosclerosis, hypertension, vasculitis, multiple sclerosis, sarcoidosis, and asthma. C. pneumoniae has a specific tropism and exhibits cytotoxic activity towards the airway epithelium, in which it proliferates and destroys infected cells by lysis. Entry of these bacteria to the human body leads to activation of first non-specific and then specific resistance mechanisms and the development of a local inflammatory process. Diagnosis of C. pneumoniae should be confirmed only after the exclusion of typical micro-organisms causing respiratory infections. It is important to pay attention to the fact that the epidemiological data on the incidence of C. pneumoniae infections in different age groups of patients are variable depending on the type of diagnostic methods used in the research. Chlamydia are resistant to most antibiotics that are routinely used in respiratory tract infections. These bacteria are susceptible to antibiotics that disrupt the synthesis of DNA and proteins, such as macrolides, tetracyclines, and fluoroquinolones.

Association of Chlamydia Pneumoniae Strain TWAR Antibody and Angiographically Demonstrated Coronary Artery Disease

Background:A recent case-control study from Finland reported a strong relationship between high antibody titers to Chlamydia pneumoniae, strain TWAR, and both chronic heart disease and acute myocardial infarction. Other studies also suggested an association between C. pneumoniae infection and coronary atherosclerosis, based on the demonstration of increased serologic titers and the detection of bacteria within atherosclerotic tissue, but this association has not been yet regarded as an established theory. The objective of this study was to investigate the relationship between C. pneumoniae immnoglobulin G antibody titers and angiographically diagnosed coronary artery disease. Method:Coronary angiography was performed. Controls (n=89 were co- ronary angiographically normal cases and coronary artery disease (n=115 was diagnosed if coronary artery luminal diameter is obstructed more than 50% in more than one coronary artery. Micro-IF assay was used to measure C. pneumoniae TWAR antibodies. The sera were titrated in two-fold dilutions starting from 1 in 8, and a titre of 1 in 8 or more was judjed positive. Results:The estimated risk of coronary artery disease, adjusted for age and gender, was greater among subjects with high (≥1:128 antibody titers than with low (≤1:8 antibody titers (relative risk, 7.9:95% confidence interval, 1.3-47.9. Conclusion:These results support an association between infection with C. pneumoniae and coronary artery disease only in high (≥1:128 antibody titers. (Korean Circulation J 1999;29(10 :1076-1081

Preclinical models for Chlamydia pneumoniae and cardiovascular disease: hypercholesterolemic mice

Seroepidemiologic studies have shown an association of Chlamydia pneumoniae antibody with atherosclerosis. Compelling additional evidence has accumulated, in that the organism has been found within atherosclerotic lesions throughout the arterial tree by multiple methods. C. pneumoniae has also been isolated from coronary and carotid atheromatous plaques. Although these studies support a potential role for C. pneumoniae in atherogenesis, confirmation of a causal relationship requires the use of animal models and intervention studies. We have focused on the evaluation of mouse models to address the hypothesis that, following upper respiratory tract infection, lung macrophages are infected, disseminate to the aorta, and alter the onset or progression of atherogenesis. ApoE-deficient knock-out and C57BL/6J mice were used. The apoE-deficient mouse develops atherosclerotic lesions spontaneously on a regular diet in a time- and age-dependent manner. This knock-out strain was developed on the background of the C57BL/6J mouse, which only develops atherosclerosis on a high-fat/high-cholesterol diet. To investigate whether infected macrophages constitute a vehicle for dissemination of C. pneumoniae in vivo, mice were inoculated intranasally or intraperitoneally. The organism was detected in harvested alveolar and peritoneal macrophages at all time points following intranasal and intraperitoneal inoculations, respectively, and in peripheral blood mononuclear cells following inoculation by both routes. In another experiment, alveolar and peritoneal macrophages from intranasally and intraperitoneally inoculated mice were adoptively transferred by intraperitoneal injection to uninfected mice. Subsequently, C. pneumoniae was detected in lung, spleen, abdominal lymph nodes and/or thymus of recipient mice. In control experiments, UV-inactivated C. pneumoniae DNA was not detected in alveolar or peritoneal macrophages beyond 5 min after inoculation in vivo. These cumulative results demonstrate that C. pneumoniae infects macrophages in vivo and that macrophages can serve as a vehicle for dissemination to other sites. To answer the question of whether the organism disseminates to and persists in the aorta, 8-week-old mice were infected intranasally. Following single or multiple inoculations in apoE-deficient mice, C. pneumoniae was detected in the lung and aorta for 20 weeks postinfection. In contrast, in C57BL/6J mice, the organism did not persist in the aorta following a single intranasal inoculation, but could be detected up to 7 weeks postinfection in multiply inoculated mice. Significantly, in apoE-deficient mice with developed atherosclerotic lesions, the organism was found in foam cells within the lesions by immunocytochemical staining. These studies show that persistent C. pneumoniae infection occurs in atherosclerotic lesions in the aorta in the apoE-deficient knock-out mouse model. Infection of the aorta also occurred in C57BL/6J mice but was more transient. Both models should be useful in studying the pathogenic role of C. pneumoniae in atherogenesis and for determining if therapy prevents dissemination of infection. To this end, we have evaluated the susceptibility of C. pneumoniae to roxithromycin, a new macrolide, in vitro in cell culture and in vivo in the apoE-deficient mouse model. In vitro results compare favorably with other new macrolides, quinolines, and tetracyline. Preliminary studies in the apoE model of persistent infection suggest that the organism is detected less frequently in the lung and aorta by PCR following treatment. These promising preliminary studies warrant further investigation.

Mycoplasma contamination of Chlamydia pneumoniae isolates.

We examined 6 C. pneumonia isolates from The American Type Culture Collection (ATCC) and 2 Finnish isolates for Mycoplasma contamination. Three of the ATCC isolates and both of the Finnish isolates were Mycoplasma-contaminated. The contaminants were characterized by means of growth in BEa and BEg media, immunoblotting, polymerase chain reaction and pulsed field gel electrophoresis. Two of the 6 ATCC isolates [ATCC VR1355 (TWAR strain 2043) and ATCC VR1356 (TWAR strain 2023)] were infected with Mycoplasma hominis and 1 isolate [ATCC VR2282 (TWAR strain TW183)] was contaminated with both Mycoplasma hominis and Mycoplasma orale, whereas 3 of the ATCC isolates [ATCC VR1310, ATCC VR1360 (TWAR strain CM-1) and ATCC 53592 (TWAR strain AR39)] were not contaminated. The Finnish C. pneumoniae isolates Kajaani 6 and Parola were found to be contaminated with M. hominis and M. orale, respectively. The contamination of C. pneumoniae stock cultures, frequently used in the microimmunofluorescence test, with human pathogens, could pose a serious problem in C. pneumoniae serology.

Roles of infectious agents in atherosclerosis and restenosis: an assessment of the evidence and need for future research.

The past few years have witnessed a resurgence of interest in the possibility that infectious processes may contribute to arterial diseases, including atherosclerosis and restenosis after arterial intervention. The recent recognition that Helicobacter pylori contributes to peptic ulcers illustrates how a disease previously believed to result primarily from excessive gastric acid production often involves a microbial pathogen. Although hypercholesterolemia clearly predisposes to development of coronary heart disease, many patients with arterial pathology have serum cholesterol levels within or below the average range. Coronary heart disease frequently affects individuals who lack other traditional risk factors as well. These findings suggest that heretofore unrecognized risk factors may also contribute to the pathogenesis of coronary heart disease. At a recent Special Emphasis Panel convened by the National Heart, Lung, and Blood Institute, a number of experts reviewed the evidence for links between infectious processes and atherosclerosis and restenosis. This report will summarize and examine critically the evidence for involvement of infectious agents in arterial diseases based on the deliberations of this expert panel. It will also highlight some of the unanswered questions in this area that may warrant further investigation. Many reports of associations between a wide variety of infectious agents and atherosclerosis have recently appeared. An exhaustive evaluation of each of these purported associations lies beyond the scope of this survey. Rather, we will concentrate particularly on two particular infectious agents, one viral and one bacterial, currently linked with atherogenesis and supported by emerging evidence. Specifically, this report will focus primarily on herpesviruses, particularly cytomegalovirus (CMV), as an example of a viral agent and Chlamydia pneumoniae ( C pneumoniae , also known as the TWAR strain on the basis of its original laboratory designation) as an example of a bacterial pathogen. Although the preponderance of recent studies have examined CMV and Chlamydia , …

The influence of sexual and social factors on the risk of Chlamydia trachomatis infections: a population-based serologic study.

Genital chlamydia infections often are asymptomatic, which promotes their spread in the population. In women, the possible consequences of infection are pelvic inflammatory disease and infertility. Most studies on the prevalence of Chlamydia trachomatis have been based on clinical series, and prevalences tend to vary with the clinical setting. Few seroepidemiologic studies have emerged from industrialized countries. To assess the prevalence of Chlamydia trachomatis using culture and serology, and its relationship with possible risk factors. This was a population-based study involving completion of a self-administered questionnaire, analysis of cervical samples for Chlamydia trachomatis, and serologic tests for Chlamydia trachomatis antibodies. The prevalence of Chlamydia trachomatis infection was 2.7%, and the seroprevalence was 24.7% among the sexually active women. Seropositivity was correlated with sexual behavior variables, and the incidence of serologic cross-reactivity with respiratory infections (strain TWAR) was low. Multivariate logistic regression analysis showed the number of sexual partners, age at first coitus, history of therapeutic abortion, and previous pelvic inflammatory disease to be independently correlated with seropositivity. Early sexual experience and multiple lifetime sexual partners are independent risk factors for Chlamydia trachomatis infection.

Epidemiology and Treatment of Chronic Bronchitis and Its Exacerbations

Epidemiology and Treatment of Chronic Bronchitis and Its Exacerbations

775-5 Increased Incidence of Chlamydia Bacteria Detected within Coronary Arteries of Patients with Atherosclerotic Versus Transplant Induced Coronary Artery Disease

Previous work has suggested an association between Chlamydia pneumoniae infection and coronary atherosclerosis, based on the demonstration of increased serologic titers and the detection of bacteria within atherosclerotic tissue. We sought to strengthen a possible etiologic link by comparing the incidence of Chlamydia infection in coronary atherosclerotic tissue to that in coronary arteries of patients with non-atherosclerotic cardiovascular disease. Coronary tissue specimens obtained from 90 consecutive patients (mean age = 57 yrs) with symptomatic coronary artery disease undergoing directional coronary atherectomy were tested for the presence of Chlamydia species by direct immunofluorescence using mouse monoclonal antibody. Immunofluorescence was positive in 68 (76%), equivocal in 5 (6%) and negative in 19 (21 %) of specimens. Polymerase chain reaction confirmed the specific Chlamydia strain TWAR in 2 cases. No clinical factors except the presence of a primary non-testenotic lesion (odds ratio = 3.0, p = 0.057) predicted the detection of Chlamydia. As a control, coronary tissue specimens from 11 patients with previous cardiac transplantation and subsequent transplant-induced coronary artery disease were also tested. Direct immunofluorescence performed on these diseased coronary artery segments was negative for Chlamydia in every case (p = 0.0001 compared with atherosclerotic specimens). This high incidence of Chlamydia detected only in coronary arteries diseased by atherosclerosis suggests an etiologic role for Chlamydia infection in the development of coronary atherosclerosis, which should be further studied.

Radiographic appearance of Chlamydia pneumoniae (TWAR strain) respiratory infections. CBPIS Study Group. Community-based Pneumonia Incidence Study.

To report the spectrum of radiographic findings associated with a new respiratory pathogen: Chlamydia pneumoniae (TWAR strain). Radiographs of 55 adult patients hospitalized with serologic evidence of C pneumoniae were retrospectively reviewed. On the basis of serologic criteria, two types of acute respiratory infection are possible: primary (first exposure) infections and recurrent, acute infection in a previously exposed individual. In the primary group, alveolar opacities (65%) with a unilateral distribution (71%) were most common at admission. Cavitary disease and hilar or mediastinal lymphadenopathy were uncommon. Small to medium-sized pleural effusions were common in both primary and recurrent groups during hospitalization. Also, both groups tended to progress to bilateral, mixed, interstitial and alveolar changes during the course of infection. Different radiographic patterns exist for the two types of acute C pneumoniae infection.

Mycoplasma pneumoniae and Chlamydia pneumoniae Strain TWAR Infections in U.S. Marine Corps Recruits

Paired sera from 208 healthy Marine Corps recruits undergoing 11 weeks of basic training in San Diego during 1989 were studied by complement fixation and microimmunofluorescence techniques for antibody to Mycoplasma pneumoniae and Chlamydia pneumoniae strain TWAR infections. Upon entering training, 52.7% and 64.4% of the recruits had evidence of prior infection with M. pneumoniae and C. pneumoniae, respectively. At the end of training, 5.9% of recruits had evidence of new infections with M. pneumoniae (4-fold antibody rise) and 3.8% had evidence for new infections with C. pneumoniae (4-fold antibody rise). Recruits with evidence of previous infection with C. pneumoniae had a lower relative odds of new infection during training with this agent (odds ratio = 0.07, 95% confidence interval 0.00-0.61). These data demonstrate that, like their counterparts in Scandinavia, U.S. military recruits also suffer from C. pneumoniae infections. Both M. pneumoniae and C. pneumoniae should be considered as potential causes of respiratory disease among U.S. military trainees.

Chlamydia pneumoniae strain TWAR pharyngitis in US Air Force basic trainees

Chlamydia pneumoniae has recently been shown to be a cause of pharyngitis. Because the impact of this pathogen on United States Air Force basic trainees is unknown, the authors undertook a prospective study to evaluate the prevalence of C pneumoniae. Of 118 asymptomatic basic trainees, 43% had preexisting antibodies to C pneumoniae and 0.9% had serologic evidence of C pneumoniae infection. Of 226 symptomatic basic trainees, only four (1.8%) met the criteria for serologic evidence of acute C pneumoniae infection. No other cause of pharyngitis was found in three of four of these basic trainees. Three of the trainees with C pneumoniae infection had hoarseness and all had a dry cough. All symptoms resolved without specific antichlamydial therapy. Chlamydia pneumoniae was an uncommon cause of pharyngitis in basic trainees, appearing as a mild, self-limiting illness.

Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis

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.

Evidence for Chlamydia pneumoniae of non-human origin.

This paper describes the characterization and taxonomic status of N16, a chlamydial isolate from the respiratory tract of a horse. N16 contains plasmid DNA, has normal elementary body morphology and its inclusions do not stain with iodine. Its major outer-membrane protein (MOMP) gene was completely sequenced and compared with the MOMP genes of Chlamydia pneumoniae, C. psittaci, C. trachomatis and C. pecorum. This analysis revealed that N16 is closely related to the TWAR strain of C. pneumoniae (94.5% and 94.4% DNA homology with TWAR isolates IOL-207 and AR-39 respectively). By comparison, N16 shows between 72.1% and 73.7% DNA homology with C. psittaci strains, 70.9% and 71.1% homology with C. pecorum strains LW613 and 1710S and 69.2% homology with C. trachomatis serotype E. The MOMP gene of N16 shares 93.8% DNA homology with the MOMP gene of a chlamydial isolate KC from the conjunctiva of a koala. Monoclonal antibodies raised to C. pneumoniae IOL-207 and shown to be C. pneumoniae-specific confirmed that N16 was more closely related to C. pneumoniae than to C. psittaci. Thus DNA homology and monoclonal antibody data both suggest that horse chlamydiae, as exemplified by N16, form a new second strain of C. pneumoniae. This species is probably more widespread and diverse than the current literature would suggest.

An Epidemic of Infections Due to Chlamydia pneumoniae in Military Conscripts

A prospective observational study of an epidemic of infection due to Chlamydia pneumoniae strain TWAR in Finnish military trainees provided new information on immunity following infection, the range of clinical syndromes and complications, and cell culture isolation. One-half of the trainees studied (43 of 86) had laboratory evidence of C. pneumoniae infection. The etiologic association of C. pneumoniae with disease was strengthened by the sharp increase in cases of pneumonia and in outpatient visits for acute respiratory disease along with the laboratory evidence of infection. The pattern of serological response suggested that 23 of the trainees had a primary TWAR infection and 20 had a reinfection. Evidence that prior infection modified the illness included the frequency of hospitalization (12 with primary infections vs. 1 with reinfection), the development of pneumonia (10 vs. 0), and the requirement for repeated courses of antibiotic therapy (13 courses vs. 0). Isolation was more frequent in HL cells (n = 25) than in HeLa 229 cells (n = 10).

A mouse model of Chlamydia pneumoniae strain TWAR pneumonitis

Chlamydia pneumoniae is a common cause of acute respiratory infections in humans. We evaluated mice as experimental animals for C. pneumoniae. Intranasal inoculation of Swiss Webster mice with C. pneumoniae induced a prolonged course of lung infection, as demonstrated by reisolation of organisms from lungs (at 42 days) and persistence of lung pathology (> 60 days). The lung pathology was characterized by patchy interstitial pneumonitis with predominantly polymorphonuclear leukocyte infiltration in the early and mononuclear cell infiltration in the later stages of infection. Inoculated mice developed serum immunoglobulin G antibody responses and partial resistance against rechallenge inoculation. The other mouse strains tested, Icr, BALB/cAnN, C57BL/6N, C3H/HeN, and B6C3F1, were shown to be susceptible to C. pneumoniae. The mouse model should be useful for investigating the immunopathogenesis of C. pneumoniae infections.

Chlamydia pneumoniae infection in acute exacerbations of COPD

Chlamydia pneumoniae, strain TWAR, is a frequent causative agent of acute respiratory disease. We assessed the incidence and prevalence of Chlamydia pneumoniae infections in COPD. We studied, from January 1990 to May 1991, 142 out-patients with acute purulent exacerbations of chronic obstructive pulmonary disease (COPD) and 114 healthy control subjects. Oropharyngeal swab specimens were collected at each exacerbation and analysed using a high definition monoclonal indirect fluorescent antibody test for Chlamydia pneumoniae identification. Immunoglobulins G and M (IgG and IgM) fractions of antibodies to Chlamydia pneumoniae were studied by microimmunofluorescence test. Prevalence of specific IgG was 63% in COPD, and 46% in controls (Chi-squared test p = 0.007). Moreover, mean titre of IgG was significantly higher in COPD than in controls. Five patients were positive for specific IgM (> or = = 1:16), and one had a fourfold increase of IgG titre; four of these patients had been treated with ciprofloxacin 1 g.day-1 for 10 days, and two with erythromycin, 3 g.day-1 for 14 days, with remission of signs and symptoms of exacerbation. Chlamydia pneumoniae identification was always negative. Our data suggest that Chlamydia pneumoniae infection is a rather frequent event in COPD, since at least 4% of exacerbations may be associated with it.

Infections caused by Chlamydia pneumoniae strain TWAR.

Journal Article Infections Caused by Chlamydia pneumoniae Strain TWAR Get access J. Thomas Grayston J. Thomas Grayston From the Department of Epidemiology, University of Washington, Seattle, Washington Reprints or correspondence: Dr. J. Thomas Grayston, Department of Epidemiology, SC-36, University of Washington, Seattle, Washington 98195. Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, Volume 15, Issue 5, November 1992, Pages 757–763, https://doi.org/10.1093/clind/15.5.757 Published: 01 November 1992 Article history Received: 02 June 1992 Published: 01 November 1992

Association of Chlamydia pneumoniae (Strain TWAR) infection with wheezing, asthmatic bronchitis, and adult-onset asthma : Hahn DL, Dodge RW, Golubjatnikov R: J Am Med Assoc 266:225–230, 1991

Association of Chlamydia pneumoniae (Strain TWAR) infection with wheezing, asthmatic bronchitis, and adult-onset asthma : Hahn DL, Dodge RW, Golubjatnikov R: J Am Med Assoc 266:225–230, 1991

The prevalence and regional distribution of antibodies against Chlamydia pneumoniae (strain TWAR) in Finland in 1958.

The occurrence of nonavian 'ornithosis' was reported in Scandinavia at the end of the 1950s. In order to find out whether Chlamydia pneumoniae had been present in Finland, we examined the IgG antibody prevalence to C pneumoniae in samples representing the whole rural population of Finland in 1958. The total number of sera studied using micro-immunofluorescence was 2000. Trend-surface analysis was used to examine the regional patterns of antibody prevalence. C pneumoniae antibodies were present throughout the country. The mean antibody prevalence was 56% among adults and 27% among children. Thus the possible role of C pneumoniae in nonavian 'ornithosis' in Finland between 1958 and 1960 cannot be excluded.

Development of an enzyme immunoassay to detect antibody to Chlamydia pneumoniae strain twar and its application in a limited seroepidemiological survey

A non-competitive enzyme immunoassay (EIA) was developed to detect IgG antibody to the recently-described species Chlamydia pneumoniae strain TWAR. Purified elementary bodies of the organism were used as capture antigen. Cross-reacting antibody to Chlamydia trachomatis was detected in the assay by running a parallel EIA for IgG antibody to C. trachomatis. The C. pneumoniae assay was validated by comparing the results on 60 selected sera with those obtained with the microimmunofluorescence test. The comparison indicated that the EIA had a sensitivity of 88%, specificity of 100% and overall correlation with micro-immunofluorescence of 93%. The assay was applied to 352 sera from 3 populations within Australasia in a limited survey to determine the extent of exposure to this organism. Prevalence rates of up to 55% were found, suggesting that a significant amount of respiratory disease in the region may be due to C. pneumoniae strain TWAR.