Chlamydia pneumoniae strain TWAR, the new third species of Chlamydia, is a common cause of pneumonia and other acute respiratory tract infections. About 10% of hospitalized and outpatient pneumonia cases have been associated with TWAR infection. TWAR is among the four or five most commonly identified causes of all pneumonia. Most TWAR infections are mild or asymptomatic, but occasionally severe pneumonia with death has been observed. Laboratory diagnosis is not generally available. Vigorous treatment with tetracycline or erythromycin is recommended. Both epidemic and endemic infections have been described in North America and the Nordic Countries. Population prevalence antibody studies suggest that TWAR infection is wide-spread throughout the world, that nearly everyone is infected and reinfected during their life-time, and that infection is common in all ages except those less than 5 years in temperate zone countries. The infection is transmitted from person to person, apparently with a long incubation period.

Chlamydia pneumoniae (TWAR) is a recently recognized third species of the genus Chlamydia that causes acute respiratory disease. It is distinct from the other two chlamydial species that infect humans, C. trachomatis and C. psittaci, in elementary body morphology and shares less than 10% of the DNA homology with those species. The organism has a global distribution, with infection most common among children between the ages of 5 and 14 years. In children, TWAR infection is usually mild or asymptomatic, but it may be more severe in adults. Pneumonia and bronchitis are the most common clinical manifestations of infection, and TWAR is responsible for approximately 10% of cases of pneumonia and 5% of cases of bronchitis in the United States. The microimmunofluorescence serologic assay is specific for TWAR and can distinguish between recent and past infections. The organism can be isolated in cell culture; however, PCR techniques have recently facilitated its detection in tissues and clinical specimens.

Cardiovascular disease, of which atherosclerosis is an important component, is the leading cause of death in the western world. Although there are well-defined risk factors for atherosclerosis, these factors do not account for all incidences of the disease. Because atherosclerotic processes are typified by chronic inflammatory responses, which are similar to those that are elicited by chronic infection, the role of infection in promoting or accelerating atherosclerosis has received renewed attention. This review focuses on the accumulating evidence that chronic infection with Chlamydia pneumoniae, a ubiquitous human respiratory pathogen, might contribute to atherosclerotic lesion progression.

No abstract

Chlamydia pneumoniae has been postulated to cause systemic disease by infection of monocytes/macrophages and spread via the blood or lymphatics. To investigate how C. pneumoniae disseminates, the ability of the organism to infect murine macrophages in vivo and whether infection can be transferred via macrophages were determined. C. pneumoniae was detected by direct plating, isolation, and polymerase chain reaction in alveolar macrophages from intranasally inoculated mice and peritoneal macrophages from intraperitoneally inoculated mice. C. pneumoniae were also detected in peripheral blood mononuclear cells, but not plasma, of intranasally and intraperitoneally inoculated mice. When alveolar or peritoneal macrophages were adoptively transferred by intraperitoneal injection from infected to uninfected mice, C. pneumoniae DNA was detected by polymerase chain reaction in lung, thymus, spleen, and/or abdominal lymph nodes. These results demonstrate the ability of C. pneumoniae to infect macrophages in vivo and to disseminate systemically via infected macrophages by hematogenous and lymphatic routes.

Six of the 7 (86%) atheroma, 2 of the 11 (18%) with intimal thickening, and none of the 31 normal-appearing coronary samples were positive. Four were positive by PCR for cytomegalovirus, 2 from diseased arteries and 2 from normal arteries. Examination of the adjacent left coronary artery sample with a fat stain found abnormalities in 25 of the patients, but 19 still showed no evidence of atherosclerosis as a result of either examination. Thus, C. pneumoniae is found in coronary lesions in young adults with atherosclerosis but is not found in normal-appearing coronary arteries of both persons with and without other evidence of atherosclerosis.A single cause for lesions of atherosclerosis has, thus far, not been found. A number of risk factors have been discovered that enhance the rate of progression of atherosclerotic lesions and increase the frequency of its sequellae, such as myocardial infarction. The concept that causation of atherosclerosis likely involves several factors is now considered reasonable.

Accumulating evidence supports an association between Chlamydia pneumoniae infection and atherosclerosis. To determine whether there is a causal relationship, the effects of chronic infection with C. pneumoniae on the development of atherosclerosis in apolipoprotein E (apoE)-deficient mice were evaluated. Eight-week-old male apoE-deficient mice were inoculated intranasally with C. pneumoniae three times, at 8, 9, and 10 weeks of age. The combined area of atherosclerotic lesions in the lesser curvature of the aortic arch was measured en face by computer-assisted morphometry. The lesion area was 2.4-fold greater (P=.05) at 16 weeks of age and 1.6-fold greater (P=.05) at 20 weeks of age in infected mice than in control mice. There were no differences in total plasma cholesterol levels between groups. This study demonstrates that C. pneumoniae infection accelerates the progression of atherosclerosis in the aortic arch of apoE-deficient mice.

It is currently unclear what causes the chronic inflammation within atherosclerotic plaques. One emerging paradigm suggests that infection with bacteria and/or viruses can contribute to the pathogenesis of atherosclerosis either via direct infection of vascular cells or via the indirect effects of cytokines or acute phase proteins induced by infection at non-vascular sites. This paradigm has been supported by multiple epidemiological studies that have established positive associations between the risk of cardiovascular disease morbidity and mortality and markers of infection. It has also been supported by experimental studies showing an acceleration of the development of atherosclerosis following infection of hyperlipidaemic animal models. There are now a large number of different infectious agents that have been linked with an increased risk of cardiovascular disease. These include: Chlamydia pneumoniae, Porphyromonas gingivalis, Helicobacter pylori , influenza A virus, hepatitis C virus, cytomegalovirus, and human immunodeficiency virus. However, there are significant differences in the strength of the data supporting their association with cardiovascular disease pathogenesis. In some cases, the infectious agents are found within the plaques and viable organisms can be isolated suggesting a direct effect. In other cases, the association is entirely based on biomarkers. In the following review, we evaluate the strength of the data for individual or groups of pathogens with regard to atherosclerosis pathogenesis and their potential contribution by direct or indirect mechanisms and discuss whether the established associations are supportive of the infectious disease paradigm. We also discuss the failure of antibiotic trials and the question of persistent infection.