Guest guest Posted August 19, 2005 Report Share Posted August 19, 2005 ANTIMICROBICS AND INFECTIOUS DISEASES NEWSLETTER Editor-in-Chief W. Stratton, MD Vanderbilt University School of Medicine Nashville, Tennessee Full editorial board appears on back cover Volume 18, Number 7 July 2000 W. Stratton, MD Vanderbilt University School of Medicine Nashville, TN 37232 Introduction Chlamydia pneumoniae was initially recognized as a cause of acute lower respiratory tract infections such as pneu- monia and bronchitis in both adults and children (1-7), hence the species name “pneumoniae.” Moreover, C. pneu- moniaewas noted in some individuals to cause a persistent respiratory tract infection following an acute infection (8), which is entirely consistent with the known chronic nature of chlamydial infections (9,10). In addition, C. pneu- moniaehas been shown to establish a subclinical asymptomatic respiratory tract infection (11). Pathogenesis of Chronic Chlamydial Infections Establishment of persistent low-grade infections in the lung by C. pneumoniae creates an important factor for the pathogenesis of this microorganism. The ability of C. pneumoniaeto infect a wide variety of human cells, including epithelial, endothelial, and smooth mus- cle cells as well as macrophages and monocytes, is well documented (12- 20). The infection of macrophages, in particular, allows C. pneumoniaeto enter the circulation from pulmonary tissues and cause systemic dissemina- tion. The tendency for C. pneumoniae to disseminate from the initial site of infection in the lung has been described in the murine model of infection (21,22). Similar dissemination is presumed to occur in humans. Indeed, the presence of C.pneumoniaeDNAin peripheral blood mononuclear cells (PBMCs) has been well documented (23-29). More- over, the viability of C. pneumoniaein circulating PBMCs has recently been established (30). The ability of C. pneu- moniaeto cause persistent infections combined with its ability to disseminate via the vascular system has raised ques- tions as to the role of this pathogen in a number of chronic human diseases (31- 33). Viable C. pneumoniaecirculating in PBMCs may reach various human tissues after an inflammatory trigger event occurs in the tissue and then cause chronic infection in the tissue. This might create or worsen a chronic disease process. The purpose of this article is to review the association of C. pneumoniaewith chronic human diseases. Chronic Lung Diseases The predilection of C. pneumoniaeto cause acute respiratory tract infections combined with its persistent nature suggests that it might play a role in chronic lung diseases (34). Chronic obstructive pulmonary disease (COPD) is a slowly developing irreversible and generally progressive chronic lung dis- ease in which three disorders are com- monly included: chronic bronchitis, peripheral airway disease, and emphy- sema. Indeed, C. pneumoniaehas been found to be a frequent cause of acute exacerbations of COPD (35). Accord- ingly, it has been suggested that C. pneumoniaemay have a role in the pathogenesis of COPD (36). Immuno- histochemical staining for C. pneumo- niaeis increased in lung tissue from subjects with COPD, suggesting that persistent infection with this organism is common (37). In addition, morpho- logical findings by electron microscopy in pulmonary emphysema reveal aberrant chlamydiaethat are identical to those seen in atherosclerosis (38). Persistent low-grade infection of the lung by C. pneumoniaeis thus likely to contribute to chronic lung disease and, in some instances, may even be causal. Chronic Otolaryngeal Diseases Otolaryngeal infections include sinusitis, otitis media, pharyngitis, tonsillitis, and laryngitis. These infections may be acute, recurrent, or chronic. The seroprevalence of antibodies to C.pneumoniaesuggests that this microorganism is an important and common pathogen of otolaryngeal disease (39). C. pneumoniaehas been isolated from both acute and chronic otitis media (40,41), and polymerase chain reaction (PCR) studies have confirmed and extended these early observations (42,43). Isolation of C. pneumoniaefrom the maxillary sinus has been described in one case report (44), but additional studies evaluating the role of C. pneumoniaein sinusitis have not been done. C. pneumoniaehas been isolated from pharyngeal tissue biopsies as well as demonstrated by Association of Chlamydia pneumoniaewith Chronic Human Diseases ANTIMICROBICS AND INFECTIOUS DISEASES NEWSLETTER In This Issue Association of Chlamydia pneumoniaewith Chronic Human Diseases. . . . . . . . . . . . . . . 49 W. Stratton, MD Editor-in-Chief W. Stratton, MD Vanderbilt University School of Medicine Nashville, Tennessee Full editorial board appears on back cover Volume 18, Number 7 July 2000 AIDIEX 18(7)49-56,2000 ©2001 Elsevier Science Inc. 1069-417X/00 (see frontmatter) 49 50 1069-417X/00 (see frontmatter) ©2001 Elsevier Science Inc. Antimicrobics and Infectious Diseases Newsletter 18(7) 2000 immunohistochemical methods in patients with chronic pharyngitis (45). Similarly, immunohistochemical anal- ysis and PCR have demonstrated C. pneumoniaein adenoid tissue from children undergoing adenoidectomy for hyperplastic adenoids (46,47). Clearly C. pneumoniaeis present in otolaryn- geal tissues and plays a role in both acute and chronic infections as well as a possible role in a hyperplastic response. Asthma Infection has long been thought to play a role in asthma (48). For example, res- piratory tract infections are thought to precipitate wheezing in many asthmatic patients. The recent use of PCR to diag- nose viral infections of the respiratory tract has documented the role of rhino- virus and respiratory syncytial virus in acute exacerbations of asthma (49). As C. pneumoniaeis a pathogen causing acute and chronic respiratory tract infections, it may play a similar role in asthma. One of the first studies to investigate this possibility found that there is an association of C. pneumoni- aeinfection with wheezing, asthmatic bronchitis, and adult-onset asthma (50). Not only did C.pneumoniaeappear to exacerbate asthma, it seemed in some patients to initiate asthma. The authors concluded that repeated or prolonged exposure to C. pneumoniaemay have a causal association with wheezing, asth- matic bronchitis, and asthma. Other investigators have confirmed the asso- ciation of C. pneumoniaewith acute exacerbations of asthma in both adults and children (51-58). Several studies suggest that antimicrobial therapy against C. pneumoniaeis beneficial in the course of reactive airway disease (59-61). Whether or not C. pneumoniae plays a causal role in addition to its role in exacerbations of asthma remains to be determined. Atherosclerosis Despite significant advances in our understanding of the various risk fac- tors involved in atherosclerosis, there are significant gaps in the elucidation of the etiology of vascular injury and atherogenesis. Chronic infection of vas- cular tissue has received considerable attention recently as an inducer of vas- cular injury and subsequent develop- ment of atherosclerosis. Although infection with a variety of infectious agents such as cytomegalovirus has been implicated in atherogenesis, the best evidence to date links the presence of C. pneumoniaewith the pathogenesis of atherosclerosis. Saikku et al. (62,63) first reported an association between anti-C. pneumoniaeantibody titers and coronary artery disease. In a 1999 review, Wong, Gallagher, and Ward (64) reported that 21 of 27 studies showed “some sort of positive serological association between positive anti-C. pneumoniaetiters and atherosclerosis.” Similar results have been reported in cerebrovascular accidents with a num- ber of studies showing a positive correlation with anti-C. pneumoniae antibodies (65-67). Direct evidence of C. pneumoniaeinfection of blood vessels is provided by studies using electron microscopy (68,69,74), PCR (69,71-78,82), immunohistochemistry (68,70-75,80,82), reverse transcriptase PCR (79), and cultures (75,77,80,81). Finally, animal models support a role for C. pneumoniaein the pathogenesis of atherosclerosis (83-85). Neurological Diseases The serologic association of C. pneu- moniaeinfections with neurological diseases began with several individual case reports that linked this micro- organism with Guillain-Barre syndrome (86) and lumbosacral meningoradiculi- tis (87). These observations were followed by additional reports asso- ciating C. pneumoniaewith meningitis (88,89). The association of chlamydial infections with neurological syndromes has been strengthened by a large sero- logical survey of patients with neuro- logical disease (90). These observations suggest that C.pneumoniaemay be more prevalent as an associated agent in central nervous system (CNS) dis- eases than appreciated (90) and that chlamydial infections should be includ- ed in the differential diagnosis of neuro- logical syndromes (91). The first direct evidence that C. pneumoniaeinfection may be risk factor for a chronic neuro- logical disease was a study that demon- strated that C. pneumoniaeis present, viable, and transcriptionally active in areas of neuropathy in the Alzheimer’s disease brain (92). This was followed by a report of a case in which C. pneu- moniaewas isolated from the cerebro- spinal fluid (CSF) of a patient with multiple sclerosis (MS) (93). Anti- chlamydial therapy markedly improved the course of MS in this patient. Amore extensive study by the same investiga- tors demonstrated that infection of the CNS is a frequent occurrence in MS patients (94).Other investigators have confirmed the presence of C. pneumo- niaein CSF from MS patients (95,96) as well as in CSF from patients with other types of neurological disease (97). Additional case reports for meningo- encephalitis and encephalomyelitis (98,99) suggest that C.pneumoniaeis a neurotrophic pathogen and thus may play a role in a variety of chronic neurological diseases. Chronic Rheumatological Diseases Rheumatological diseases include those diseases that involve the connective tissues. Joints and related structures of NOTE: No responsibility is assumed by the Publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. No suggested test or procedure should be carried out unless, in the reader’s judgment, its risk is justified. Because of rapid advances in the medical sciences, we recommend that the independent verification of diagnoses and drug doses should be made. Discussions, views, and recommendations as to medical procedures, choice of drugs, and drug dosages are the responsibility of the authors. Antimicrobics and Infectious Diseases Newsletter(ISSN 1069-417X) is issued monthly in one indexed volume per year by Elsevier Science Inc., 655 Avenue of the Americas, New York, NY10010. For customer service, phone (212) 633-3950; TOLL-FREE for customers in the U.S.A. and Canada: 1-888-4ES-INFO (1-888-437-4636) or fax: (212) 633-3680. Subscriptions are available on a calendar year basis or as a rolling (anytime-start) subscription. Subscription price per year: Institutional subscription: NLG 713 (euro 323.55) for customers in Europe; ¥44,800 for Japan; and US$362 for all countries other than Europe and Japan. Personal subscription: NLG 416 (euro 188.77) for customers in Europe; ¥26,200 for Japan; and US$211 for all other countries other than Europe and Japan. Periodical postage paid at New York, NYand at additional mailingoffices. Postmaster: Send address changes to Antimicrobics and Infectious Diseases Newsletter, Elsevier Science Inc., 655 Avenue of the Americas, New York, NY10010. Antimicrobics and Infectious Diseases Newsletter 18(7) 2000 ©2001 Elsevier Science Inc. 1069-417X/00 (see frontmatter) 51 the skeleton are considered the principal connective tissues and vary widely in structure and function as well as in pre- disposition to disease. Many connective tissue diseases in humans are chronic and involve inflammation. The most common is rheumatoid arthritis (RA). RAis a chronic connective tissue dis- ease of unknown etiology which has been considered by some to be the result of a chronic inflammatory syn- ovial response to an unrecognized antigen, such as that from infectious agent(s). Vasculitis is a recognized component of many chronic rheuma- tological diseases (100) including RA (101). Vasculitis has been associated with a number of infectious agents (102). The recognition that C. pneumo- niaemay induce isolated and systemic vasculitis in small and large blood vessels (103) has therefore raised ques- tions as to its role in chronic rheuma- tological diseases. Moreover, Chlamydia species are known to cause polyarthritis in calves and sheep (104-107). Thus, it is not surprising to find that C. tracho- matisis now recognized as a cause of reactive arthritis (108-112). Similarly, C. pneumoniaealso has been associated with reactive arthritis (113-118). It is possible that C. pneumoniaecould also play a role in RA. Such a role may be secondary infection of inflamed joints, or it may be causal. The observations that antimicrobial therapy with tetracy- clines, agents active against Chlamydia species,is beneficial for some patients with rheumatoid arthritis (119-122) suggests that chlamydial infection may be a factor. In addition, C. pneumoniaehas been associated with other chronic rheumato- logical diseases. One case report has found an association of C. pneumoniae with systemic lupus erythematosus in which the patient was cured by a com- bination of clarithromycin, predniso- lone, and cyclophosphamide (123). More intriguing is the association of C. pneumoniaewith temporal arteritis. Temporal arteritis is a clinical manifes- tation of giant-cell arteritis. Giant-cell arteritis is a vasculitis of unknown etiol- ogy that predominantly affects medium- and large-sized arteries (124). Giant- cell arteritis and a closely related clini- cal syndrome, polymyalgia rheumatica, affect the elderly and often involve an acute onset with flu-like upper respira- tory tract symptoms. For this reason, an infectious process has been proposed as a trigger mechanism (125). An initial case in which C. pneumoniaeDNAwas detected in an artery specimen has been reported (126). Amore extensive inves- tigation found that C. pneumoniaewas present in temporal artery specimens from most patients with giant cell arter- itis (127). This study detected C. pneu- moniaeby both immunohistochemistry and PCR and noted that the dendritic cells in the adventitial layer of the arter- ies may represent the antigen-present- ing cells. This work further supports the association of C. pneumoniaewith chronic rheumatological diseases. Cancer Chronic infections are known to predis- pose to malignant growth. As C. pneu- moniaemay cause chronic infections, it may predispose to cancer. There is serological evidence of an association between C. pneumoniaeinfection and lung cancer. In on study, chronic C. pneumoniaeinfection was positively associated with the incidence of lung cancer and was especially increased in men younger than 60 years (128). This has been corroborated by a second study showing that chronic C. pneumo- niaeinfection is common in patients with lung cancer (129). Another sero- logical study found evidence of an asso- ciation between chronic C. pneumoniae infections and malignant lymphoma (130). In cutaneous T-cell lymphoma, there is a protein that has been identi- fied and found to be stimulatory for malignant Sezary Tcells. This protein has been termed Sezary T-cell activat- ing factor and is often present in the skin of patients with mycosis fungoides, the predominant form of cutaneous T- cell lymphoma. This Sezary T-cell acti- vating factor has been found to be a C. pneumoniae-associated protein (131). Therefore, it is possible that C. pneumo- niaemay play a role in the pathogenesis of cutaneous T-cell lymphoma. Miscellaneous Chronic Diseases C. pneumoniaehas been associated with a number of other chronic dis- eases. It is not surprising that C. pneu- moniaehas been reported as a treatable cause of chronic fatigue syndrome (132). It is likely that many chronic infections would result in patients experiencing chronic fatigue; thus, a chronic chlamy- dial infection would be expected to do the same. Fibromyalgia and other myalgia of unknown cause have been described in patients with chronic fatigue syndrome; C. pneumoniaeanti- bodies have been linked with myalgia of unknown cause, including fibromyal- gia (133). An interesting association of C. pneumoniaeinfections with diabetic nephropathy has been noted (134). This is interesting because of the possible relationship between glucose metabo- lism and chlamydial infection. For years, it has been speculated that chlamydiae are energy parasites that are totally dependent on their host cells for ATP and other high-energy intermediates (135), although this concept has been questioned recently due to the complete sequencing of genes from C. tracho- matisand C. pneumoniae. Analysis of these chlamydial genes suggests that chlamydiae have some functional capacity to produce their own ATPand reducing power (136). Nonetheless, it is clear that infection of eukaryotic cells with chlamydiae results in an increase in the rate of glycolysis and that this increase is not caused by chlamydial metabolic activity but instead is a host cell response to the infection (137,138). This might offer an advantage for chla- mydial replication in a host with diabetes and increased levels of glucose. If this were the case, chlamydial infection might be the source of the accelerated atherosclerosis known to occur in dia- betics. An association of C. pneumoniae infection with pyoderma gangrenosum/ skin ulcers in diabetic patients has been described (139,140). C.pneumoniae therefore might be an important patho- gen in diabetic patients. Finally, an association of C. pneumoniaeand interstitial cystitis has recently been described (141). Interstitial cystitis (IC) is a chronic inflammatory disease occurring primarily in females. IC is considered a sterile bladder condition characterized by symptoms of urgency, frequency, and pain. The etiology of IC is unknown, but autoimmune mecha- nisms have been thought to play a role. Analysis of urine samples of IC patients by PCR revealed that 71% of patients with IC were positive for C. pneumoni- ae(141). Therefore, bladder biopsies were done for culture of this pathogen. Of those patients with IC, 82% (14/17) 52 1069-417X/00 (see frontmatter) ©2001 Elsevier Science Inc. Antimicrobics and Infectious Diseases Newsletter 18(7) 2000 had tissue cultures positive for C. pneumoniae(141). Control patients were limited to those patients without a history of irritative voiding symptoms, transitional cell carcinoma, or recurrent urinary tract infection. In these control patients, 16% (1/6) had tissue cultures positive for C. pneumoniae. This differ- ence was statistically significant (P= 0.004). Thus, C. pneumoniaemay have a role in the pathogenesis of IC. Summary It is apparent from this review that C. pneumoniaehas been implicated in many chronic diseases of humans. Whether the role is that of innocent bystander, cause, or perhaps something in between remains to be determined. Regardless of the role of C. pneumoni- aein these or other chronic diseases, this microorganism is becoming a major health concern. Considerable resources will be needed to determine its role in human disease. If C. pneumoniaeproves to play an important role in any or all of these chronic diseases, its eventual control or eradication may do much to improve the health of countless persons. References 1. Saikku P, Wang SP, Kleemola M, et al. An epidemic of mild pneumonia due to an unusual strain of Chlamydia psittaci. J Infect Dis 1985; 151:832-839. 2. Grayston JT, Kuo C-C, Wang S-P, Altman J. Anew Chlamydia psittaci strain, TWAR isolated in acute respira- tory tract infections. N Engl J Med 1986; 315:161-168. 3. Grayston JT, LA, Kuo C-C, et al. Anew respiratory tract pathogen: Chlamydia pneumoniae strain TWAR. J Infect Dis 1990; 161:618-625. 4. Grayston JT, Aldous MB, Easton A, et al. Evidence that Chlamydia pneumo- niaecauses pneumonia and bronchitis. J Infect Dis 1993; 168:1231-1235. 5. Falk G, Heyman L, Gnarpe J, Gnarpe H. Chlamydia pneumoniae(TWAR): a common agent in acute bronchitis. Scand J Infect Dis 1994; 26:179-187. 6. Jantos CA, Wienpahl B, Schiefer HG, Wagner F, Hagemann JH. Infections with Chlamydia pneumoniae in infants and children with acute lower respirato- ry tract disease. Pediatr Infect Dis J 1995; 14:117-122. 7. Kauppinen M, Saikku P. Pneumonia due to Chlamydia pneumoniae:preva- lence, clinical features, diagnosis, and treatment. Clin Infect Dis 1995; 21(Suppl 3):S244-S252. 8. Hammerschlag MR, Chirgwin K, Roblin PM, et al. Persistent infection with Chlamydia pneumoniaefollowing acute respiratory illness. Clin Infect Dis 1992; 14:178-182. 9. Beatty WL, on RP, Byrne GI. Persistent chlamydiae, from cell culture to a paradigm for chlamydial pathogen- esis. Microbiol Rev 1994; 58:686-699. 10. Beatty WL, Byrne GI, on RP. Repeated and persistent infection with Chlamydia and the developement of chronic imflammation and disease. Trends Microbiol 1994; 2:94-98. 11. Hyman CL, Augenbraum MH, Robin PM, Schachter J, Hammerschlag MR. Asymptomatic respiratory tract infec- tion with Chlamydia pneumoniae TWAR. J Clin Microbiol 1991; 29:2082-2083. 12. Kaukoranta-Tolvanen S-S, Laitinen K, Saikku P, Leinonen M. Chlamydia pneumoniaemultiplies in human endothelial cells in vitro. Microb Pathog 1994; 16:313-319. 13. Numazaki K, Suzuki K, Chiba S. Replication of Chlamydia trachomatis and C.pneumoniaein the human monocytic cell line U-937. J Med Microbiol 1995; 42:191-195. 14. Godzik KL, O’Brien ER, Wang SK, Kuo CC. In vitro susceptibility of human vascular wall cells to infection with Chlamydia pneumoniae. J Clin Microbiol 1995; 33:2411-2414. 15. Gaydos CA, Summersgill JT, Sahney NN, JA, Quinn TC. Repli- cation of Chlamydia pneumoniaein vitro in human macrophages, endothe- lial cells, and aortic smooth muscle cells. Infect Immun 1996; 64:1614- 1620. 16. Kaukoranta-Tolvanen SS, Teppo AM, Laitinen K, Saikku P, Linnavuori K, Leinonen K. Growth of Chlamydia pneumoniaein cultured human periph- eral blood mononuclear cells and induction of a cytokine response. Microb Pathog 1996; 21:215-221. 17. Knoebel E, Vijayagopal P, Figueroa JE, DH. In vitroinfection of smooth muscle cells by Chlamydia pneumoni- ae. Infect Immun 1997; 65:503-506. 18. Fryer RH, Schwobe EP, Woods ML, Rodgers GM. Chlamydiaspecies infect human vascular endothelial cells and induce procoagulant activity. J Investig Med 1997; 45:168-174. 19. Redecke V, Dalhoff K, Bohnet S, Braun J, Maass M. Interaction of Chlamydia pneumoniaeand human alveolar macrophages: infection and inflamma- tory response. Am J Respir Cell Mol Biol 1998; 19:721-727. 20. Airenne S, Surcel HM, Alakarppa H, Laitinen K, et al. Chlamydia pneumoniae infection in human monocytes. Infect Immun 1999; 67:1445-1449. 21. Yang Z, Kuo C, Grayston JT. Systemic dissemination of Chlamydia pneumoni- ae following intranasal inoculation in mice. J Infect Dis 1995; 171:736-738. 22. Moazed TC, Kuo CC, Grayston JT, LA. Evidence of systemic dissemination of Chlamydia pneumo- niaevia macrophages in the mouse. J Infect Dis 1998; 177:1322-1325. 23. Boman J, Soderberg S, Forsberg J, et al. High prevalence of Chlamydia pneu- moniaeDNAin peripheral mononu- clear cells in patients with cardiovascular disease and in middle- aged blood donors. J Infect Dis 1998; 178:274-277. 24. Wong YK, Dawkins KD, Ward ME. Circulating Chlamydia pneumoniae DNAas a predictor of coronary artery disease. J Am Coll Cardiol 1999; 34:1440-1442. 25. Blasi F, Boman J, Esposito G, et al. Chlamydia pneumoniaeDNAdetection in peripheral blood mononuclear cells is predictive of vascular infection. J Infect Dis 1999; 180:2074-2076. 26. Bodetti TJ, Timms P. Detection of Chlamydia pneumoniaeDNAand anti- gen in the circulating mononuclear cell fractions of humans and koalas. Infect Immun 2000; 68:2744-2747. 27. Maass M, Jahn J, Grieffers J, Dalhoff K, Katus HA, Solbach W. Detection of Chlamydiapneumoniaewithin periph- eral blood monocytes of patients with unstable angina or myocardial infarc- tion. J Infect Dis 2000; 181(Suppl 3):S449-S451. 28. Boman J, Gaydos CA. Polymerase chain reaction of Chlamydia pneumoni- aein circulating white blood cells. J Infect Dis 2000; 181(Suppl 3):S452- S454. 29. Iliescu EA, Fiebig MF, Morton AR, Sankar-Mistry P. Chlamydia pneumo- niaein peripheral blood mononuclear cells in peritoneal dialysis patients. Peritoneal Dialysis Int 2000: 20:722- 726. 30. Gieffers J, Fullgraf H, Jahn J, et al. Chlamydia pneumoniaeinfection in circulating human monocytes is refrac- tory to antibiotic treatment. Circulation 2001; 103:351-356. 31. Leinonen M. Pathogenic mechanisms and epidemiology of Chlamydia pneu- moniae. Eur Heart J 1993; 14(Suppl Antimicrobics and Infectious Diseases Newsletter 18(7) 2000 ©2001 Elsevier Science Inc. 1069-417X/00 (see frontmatter) 53 K):S57-S61. 32. Ong G, BJ, Mansfield AO, son BR, -. Detection and widespread distribution of Chlamydia pneumoniaein the vascu- lar system and its possible implications. J Clin Pathol 1996; 49:102-106. 33. Stille W, Dittmann R, Just-Nubling G. Atherosclerosis due to chronic arteritis caused by Chlamydia pneumoniae: a tentative hypothesis. Infection 1997; 25:281-285. 34. Laurila AL, Von Hertzen L, Saikku P. Chlamydia pneumoniaeand chronic lung diseases. Scand J Infect Dis 1997; 104(Suppl):34-36. 35. Blasi F, Legnani D, Lombardo VM, et al. Chlamydia pneumoniaeinfection in acute exacerbations of COPD. Eur Respir J 1993; 6:19-22. 36. von Hertzen LC. Chlamydia pneumoni- aeand its role in chronic obstructive pulmonary disease. Ann Med 1998; 30:27-37. 37. Wu L, Skinner SJ, Lambie N, Vuletic JC, Blasi F, Black PM. Immunohisto- chemical staining for Chlamydia pneu- moniaeis increased in lung tissue from subjects with chronic obstructive pul- monary disease. Am J Res Crit Care Med 2000; 162:1148-1151. 38. Theegarten D, Mogilevski G, Anhenn O, Stamatis G, Jaeschock R, Morgenroth K. The role of Chlamydia in the pathogenesis of pulmonary emphysema. Electron microscopy and immunofluorescence reveal corre- sponding findings as atherosclerosis. Virchows Archiv 2000; 437:190-193. 39. Hashiguchi K, Ogawa H, Kazuyama Y. Seroprevalence of Chlamydia pneumo- niaeinfections in otolaryngeal diseases. J Laryngol Otol 106: 208-210. 40. Block SL, Hammerschlag MR, Hedrick J, et al. Chlamydia pneumoniaein acute otitis media. Pediatr Infect Dis 1997; 16:858-862. 41. Ogawa H, Hashiguchi K, Kazuyama Y. Recovery of Chlamydia pneumoniaein six patients with otitis media with effu- sion. J Laryngol Otol 1992; 106:490- 492. 42. Storgaard M, Ostergaard L, Jensen JS, et al. Chlamydia pneumoniaein chil- dren with otitis media. Clin Infect Dis 1997; 25:1090-1093. 43. Falk G, Engstrand I, Gnarpe J, Gnarpe H. Association of Chlamydia pneumo- niaewith otitis media in children. Scand J Infect Dis 1998; 30:377-380. 44. Hashigucchi K, Ogawa H, Suzuki T, Kazuyama Y. Isolation of Chlamydia pneumoniaefrom the maxillary sinus of a patient with purulent sinusitis. Clin Infect Dis 1992; 15:570-571. 45. Falk G, Engstrand I, Gad A, Gnarpe J, Gnarpe H, Laurila A. Demonstration of Chlamydia pneumoniaein patients with chronic pharyngitis. Scand J Infect Dis 1997; 29:585-589. 46. Norman E, Gnarpe J, Naas J, Gnarpe H, Karlsson MG, Wettergren B. Chlamydiapneumoniaein children undergoing adenoidectomy. Acta Paediatrica 2001; 90:126-129. 47. Engstrand I, Augustsson I, Bergemaim PO, Falck G, Gnarpe J, Gnarpe H. Demonstration of Chlamydia pneumo- niaein the adenoid from children with and without secretory otitis media using immunohistochemistry and PCR. Scand J Infect Dis 2001; 33:132-136. 48. Stenius-Aarniala B. The role of infection in asthma. Chest 1987; 91: 130-136. 49. ston SL. Influence of viral and bacterial respiratory infections on exac- erbations and symptom severity in childhood asthma. Pediat Pulmonol 1997; 16(Suppl):S88-S89. 50. Hahn DL, Dodge RW, Golubjatnikov R. Association of Chlamydia pneumoniae (strain TWAR) infection with wheez- ing, asthmatic bronchitis, and adult- onset asthma. J Am Med Assoc 1991; 266:225-230. 51. Allegra L, Blasi F, Centanni S, et al. Acute exacerbations of asthma in adults: role of Chlamydia pneumoniae infections. Eur Resp J 1994; 7:2165- 2168. 52. Hahn DL, Golubjatnikov R. Asthma and chlamydial infection: a case series. J Fam Pract 1994; 38:586-595. 53. Bjornsson E, Hjelm E, Janson C, Fridell E, Boman G. Serology of Chlamydiain relation to asthma and bronchial hyperresponsiveness. Scand J Infect Dis 1996; 28:63-69. 54. Miyashita N, Kubota Y, Nakajima M, Niki Y, Kawane H, Matsushima T, Chlamydiapneumoniaand exacerba- tions of asthma in adults. Ann Allergy, Asthma, Immunol 1998; 80:405-409. 55. Cunningham AF, ston SL, Julious SA, Lampe FC, Ward ME. Chronic Chlamydiapneumoniaeinfection and asthma exacerbations in children. Eur Respir J 1998; 11:345-349. 56. Hahn DL, Peeling RW, Dillon E, Mc R, Saikku P. Serologic markers for Chlamydia pneumoniaein asthma. Ann Allergy Asthma Immunol 2000; 84:227-233. 57. Gencay M, Rudiger JJ, Tamm M, Soler M, Perruchoud AP, Roth M. Increased frequency of Chlamydia pneumoniae antibodies in patients with asthma. Am J Respir Crit Care Med 2001; 163:1097-1100. 58. Brinke A, Van Dissel JT, Sterk PJ, Zwinerman AH, Rabe KE, Bel EH. Persistent airflow limitation in adult- onset nonatopic asthma is associated with serologic evidence of Chlamydia pneumoniaeinfection. J Allergy Clin Immunol 2001; 107:449-454. 59. Emre U, Roblin PM, Gelling M. The association of Chlamydia pneumoniae infection and reactive airway disease in children. Arch Pediatr Adolesc Med 1994; 148:727-732. 60. Hahn DL. Treatment of Chlamydia pneumoniaeinfection in adult asthma: a before-after trial. J Fam Pract 1995; 41:345-351. 61. Hahn DL, Bukstein D, in A, Zeitz H. Evidence for Chlamydia pneumo- niaeinfection in steroid-dependent asthma. Ann Allergy Asthma Immunol 1998; 80:45-49. 62. Saikku P, Leinonen M, Matrila K, et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1988; ii:983-985. 63. Saikku P, Leinonen M, Tenkanen L, et al. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki heart study. Ann Intern Med 1992; 116:273- 278. 64. Wong Y-K, Gallagher PJ, Ward ME. Chlamydia penumoniaeand athero- sclerosis. Heart 1999; 81:232-238. 65. Cook PJ, Honeybourne D, Lip GY, Beevers DG, Wise R, Davies P. Chlamydiapneumoniaeantibody titers are significantly associated with acute stroke and transient cerebral ischemia: the West Birmingham Stroke Project. Stoke 1998; 29:404-410. 66. Fagerberg B, Gnarpe J, Gnarpe H, Agewall S, Wikstrand J. Chlamydia pneumoniaebut not cytomegalovirus antibodies are associated with future risk of stroke and cardiovascular dis- ease: a prospective study in middle- aged to elderly men with treated hypertension. Stroke 1999; 30:299-305. 67. Elkind MS, Lin IF, Grayston JT, Sacco RL. Chlamydia pneumoniaeand the risk of first ischemic stroke: The Northern Manhattan Stroke Study. Stroke 2000; 31:1521-1525. 68. Shor A, Kuo C-C, Patton DL. Detection of Chlamydia pneumoniaein coronary arterial fatty streaks and atherosclero- matous plaques. South African Med J 54 1069-417X/00 (see frontmatter) ©2001 Elsevier Science Inc. Antimicrobics and Infectious Diseases Newsletter 18(7) 2000 1992; 82:158-161. 69. Kuo CC, Shor A, LA, Fukushi H, Patton DL, Grayston JT. Demonstration of Chlamydia pneumo- niaein atherosclerotic lesions of coronary arteries. J Infect Dis 1993; 167:841-849. 70. Kuo C-C, Gown AM, Benditt EP, Grayston JT. Detection of Chlamydia pneumoniaein aortic lesions of athero- sclerosis by immunocytochemical stain. Arteriosclerosis Thrombosis 1993; 13:1501-1504. 71. Kuo C-C, Grayston JT, LA, Goo YA, Wissler RW, Benditt EP. Chlamydiapneumoniae(TWAR) in coronary arteries of young adults (15- 34 years old). Proc Natl Acad Sci USA; 92:6911-6914. 72. Grayston JT, Kuo C-C, Coulson AS, et al. Chlamydia pneumoniae(TWAR) in atherosclerosis of the carotid artery. Circulation 1995; 92:3397-3400. 73. Blasi F, Denti F, Erba M, et al. Detection of Chlamydia pneumoniae but not Helicobacter pyloriin athero- sclerotic plaques of aortic aneurysms. J Clin Microbiol 1996; 34:2766-2769. 74. Juvonen J, Juvonen T, Laurila A, et al. Demonstration of Chlamydia pneumo- niaein the walls of abdominal aortic aneurysms. J Vasc Surg 1997; 25:499- 505. 75. LA, LA, Kuo C-C, DL, Lee A, Grayston JT. Isolation of Chlamydia pneumoniae from a carotid endarterectomy speci- men. J Infect Dis 1997; 176:292-295. 76. Maass M, Krause E, Engel PM, Kruger S. Endovascular presence of Chlamydia pneumoniaein patients with hemody- namically effective carotid artery steno- sis. Angiology 1997; 48:699-706. 77. Maass M, Bartels C, Engle PM, Mamat U, Sievers HH. Endovascular presence of viable Chlamydia pneumoniaeis a common phenomenon in coronary artery disease. J Am College Cardiol 1998; 31:827-832. 78. sen E, Boman J, Persson K, et al. Chlamydia pneumoniaein human abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 1998; 15:138-142. 79. Esposito G, Blasi F, Allegra L, et al. Demonstration of viable Chlamydia pneumoniaein atherosclerotic plaques of carotid arteries by reverse transcrip- tase polymerase chain reaction. Ann Vasc Surg 1999; 13:421-425. 80. Karlsson L, Gnarpe J, Naas J, et al. Detection of viable Chlamydia pneu- moniaein abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 2000; 19:630-635. 81. Apfalter P, Loidl M, Nadrchal R, et al. Isolation and continuous growth of Chlamydiapneumoniaefrom arterec- tomy specimens. Eur J Clin Microbiol Infect Dis 2000; 305-308. 82. LA, LA, Schmidt RA, et al. Specificity of detection of Chlamydiapneumoniaein cardio- vascular atheroma. J Infect Dis 2000; 181(Suppl 3):S447-S448. 83. Moazed TC, Kuo C-C, Patton DL, et al. Experimental rabbit models of Chlamydia pneumoniaeinfection. Am J Pathol 1996; 148:667-676. 84. Fong IW, Chiu B, Viina E, et al. Rabbit model for Chlamydia pneumoniae infection. J Clin Microbiol 1997; 35:48-52. 85. Muhlestein JB, JL, Hammond EH, et al. Infection with Chlamydia pneumoniaeaccelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation 1998; 96:633-636. 86. Haidl S, Ivarsson S, Bjerre I, Persson K. Guillain-Barre syndrome after Chlamydiapneumoniaeinfection. N Engl J Med 1992; 326:576-577. 87. Michel D, Antoine JC, Pozzetto B, Gaudin OG, Lucht F. Lumbosacral meningoradiculitis associated with Chlamydia pneumoniaeinfection. J Neurol Neurosurg Psychiatry 1992; 55:511. 88. Sundelof B, Gnarpe H, Gnarpe J. An unusual manifestation of Chlamydia pneumoniaeinfection: meningitis, hepatitis, iritis and atypical erythema nodosum. Scand J Infect Dis 1993; 25:259-261. 89. Socan M, Beovic B, Kese D. Chlamydia pneumoniaeand meningoencephalitis. N Engl J Med 1994; 331:406-407. 90. Koskiniemi M, Gencay M, Salonen O. Chlamydia pneumoniaeassociated with central nervous system infections. Eur Neurol 1996; 36:160-163. 91. Korman TM, Turnidge JD, Grayson ML. Neurological complications of chlamydial infections: case report and review. Clin Infect Dis 1997; 25:847- 851. 92. Balin BJ, Gerard HC, Arking EJ, et al. Identification and localization of Chlamydiapneumoniaein the Alzheimer’s brain. Med Microbiol Immunol 1998; 187:23-42. 93. Sriram S, Michell W, Stratton C. Multiple sclerosis associated with Chlamydiapneumoniaeinfection of the CNS. Neurology 1998; 50:571-572. 94. Sriram S, Stratton CW, Yao S, et al. Chlamydia pneumoniaeinfection of the central nervous system in multiple scle- rosis. Ann Neurol 1999; 46:6-14. 95. Treib J, Haass A, Stille W, et al. Multiple sclerosis and Chlamydia pneumoniae. (Letter to the Editor) Ann Neurol 2000; 47:408. 96. Layh-Schmitt G, Bendl C, Hildt U et al. Evidence for infection with Chlamydia pneumoniaein a subgroup of patients with multiple sclerosis. Ann Neurol 2000; 47:652-655. 97. Gieffers J, Pohl D, Treib J, et al. Presence of Chlamydia pneumoniae DNAin the cerebral spinal fluid is a common phenomenon in a variety of neurological diseases and not restricted to multiple sclerosis. Ann Neurol (in press). 98. Heick A, Skriver E. Chlamydia pneumoniae-associated ADEM. Eur J Neurol 2000; 7:435-438. 99. Guglielminotti J, Lellouche N, Maury E, Alzieu M, Guidet B, Offenstadt G. Severe meningoencephalitis: an unusu- al manifestation of Chlamydia pneumo- niaeinfection. Clin Infect Dis 2000; 30:209-210. 100.Hunder GG. Vasculitis: diagnosis and therapy. Am J Med 1996; 100(Suppl 2A):S37-S45. 101.Goronzy JJ, Weyand CM. Vasculitis in rheumatoid arthritis. Curr Opin Rheumatol 1994; 6:290-294. 102.Lie JT. Vasculitis associated infectious agents. Curr Opin Rheumatol 1996; 8:26-29. 103.Ljungstrom L, Franzen C, Schlaug M, Elowson S, Vidas U. Reinfection with Chlamydiapneumoniaemay induce isolated and systemic vasculitis in small and large vessels. Scand J Infect Dis 1997; 104(Suppl):S37-S40. 104.Storz J, Marriott ME, Smart RA, RV. Polyarthritis of calves: isolation of psittacosis agents from affected joints. Am J Vet Res 1966; 27:633–641. 105.Norton WL, Storz J. Observations on sheep with polyarthritis produced by an agent of the psittacosis-lymphogran- uloma venereum-trachoma group. Arthritis Rheum 1967; 10:1-12. 106.Eugster AK, Storz J. Pathogenic events in intestinal chlamydial infections lead- ing to polyarthritis in calves. J Infect Dis 1971; 123:41-50. 107.Cutlip RC, Ramsey FK. Ovine chlamy- dial polyarthritis: sequential develop- ment of articular lesions in lambs after intraarticular exposure. Am J Vet Res 1973; 34:71-75. Antimicrobics and Infectious Diseases Newsletter 18(7) 2000 ©2001 Elsevier Science Inc. 1069-417X/00 (see frontmatter) 55 108.Schachter J, MG, JP, Engleman EP, Myer KF. Isolation of bedsoniae from the joints of patients with Reiter’s syndrome. Proc Soc Exp Biol Med 1966; 122:283-285. 109.Keat A, B, R, - D. Chlamydia trachomatisin reactive arthritis. Rheumatol Int 1989; 9:197–200. 110. Hammer M, Nettelnbreker E, Hopf S, Schmitz E, Porschke K, Zeidler H. Chlamydial rRNAin the joints of patients with Chlamydia-induced arthritis and undifferentiated arthritis. Clin Exp Rheumatol 1992; 10:63–66. 111. Raham MU, Cheema MA, Schumacher HR, Hudson AP. Molecular evidence for the presence of Chlamydiain the synovium of patients with Reiter’s syndrome. Arthritis Rheum 1992; 35:521–529. 112. Schumacher HR Jr, Magge S, Chernian PV, et al. Light and electron microscopic studies on the synovial membrane in Reiter’s syndrome; immunocytochemical identification of Chlamydiaantigen in patients with early disease. Arthritis Rheum 1994; 37:710-717. 113. Gran JT, Hjetland R, ssen AH. Pneumonia, myocarditis and reactive arthritis due to Chlamydia pneumoniae. Scand J Rheumatol 1993; 22:43-44. 114. Saario R, Toivanen A. Chlamydia pneumoniaeas a cause of reactive arthritis. Br J Rheum 1993; 32:1112. 115. Braun J, Laitko S, Treharne J, et al. Chlamydia pneumoniae— a new causative agent of reactive arthritis and undifferentiated oligoarthritis. Ann Rheum Dis1994; 53:100-105. 116. Melby KK, Kvien TK, Glennas A, Anestad G. Chlamydia pneumoniaeas a trigger of reactive arthritis. Scand J Infect Dis 1999; 31:327-328. 117. Moling O, Pegoretti S, Rielli M, et al. Chlamydia pneumoniae— reactive arthritis and persistent infection. Br J Rheumatol 1996; 35:1189–1190. 118. Gerard HC, Schumacher HR, El- Gabalawy H, Goldbach-Mansky R, Hudson AP. Chlamydia pneumoniae present in the human synovium are viable and metabolically active. Microb Pathog 2000; 29:17-24. 119. Skinner M, Cathcart ES, Mills JA, Pinals RS. Tetracycline in the treatment of rheumatic arthritis: a double blind controlled study. Arthritis Rheum 1971;14:727–732. 120.Kloppenburg M, Breedveld FC, Terwiel JP, Mallee C, Dijkmans BA. Minocycline in active rheumatoid arthritis. Adouble-blind, placebo- controlled trial. Arthritis Rheum 1994; 37:626-636. 121.Tilley BC, Alarcon GS, Heyse SP, et al. Minocycline in rheumatoid arthritis. A48-week, double-blind, placebo- controlled trial. MIRATrial Group. Ann Intern Med 1995; 122:81-89. 122.O’Dell JR, Haire CE, Palmer W, Drymalski S, et al. Treatment of early rheumatoid arthritis with minocycline or placebo: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 1997; 122:81-89. 123.Takaki K, Tatuo H, Shin H, et al. A case of Chlamydia pneumoniaeand systemic lupus erythematosus (SLE) pleurisy. Kansenshogaku Zasshi 1999; 73:191-196. 124.Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33:1122-1128. 125.Russo MG, Waxman J, Abdoh AA, Serebro LH. Correlation between infection and the onset of the giant cell (temporal) arteritis syndrome: a trigger mechanism? Arthritis Rheum 1995; 38:123-192. 126.Rimenti G, Blasi F, Cosentini R, et al. Temporal arteritis associated with ChlamydiapneumoniaeDNAdetected in an artery specimen. J Rheumatol 2000; 27:2718-2720. 127.Wagner AD, Gerard HC, Fresemann T, et al. Detection of Chlamydia pneumo- niaein giant cell vasculitis and correla- tion with the topographic arrangement of tissue-infiltrating dendritic cells. Arthritis Rheum 2000; 43:1543-1551. 128.Laurila AL, Anttila T, Laara E, et al. Serological evidence of an association between Chlamydia pneumoniaeinfec- tion and lung cancer. Int J Cancer 1997; 74:31-34. 129.Koyi H, Branden E, Gnarpe J, Gnarpe H, Arnholm B, Hillerdal G. Chlamydia pneumoniaemay be associated with lung cancer. Preliminary report on a seroepidemiological study. APMIS 1999; 107:828-832. 130.Anttila TI, Lehtinen T, Leinonen M, et al. Serologic evidence of an asso- ciation between chlamydial infections and malignant lymphomas. Br J Haematol 1998; 103:150-156. 131.Abrams JT, Vonderheid EC, Kolbe S, Appelt DM, Arking EJ, Balin BJ. Sezary T-cell activating factor is a Chlamydia pneumoniae-associated protein. Clin Diagn Lab Immunol 1999; 6:895-905. 132.Chia JK, Chia LY. Chronic Chlamydia pneumoniaeinfection: a treatable cause of chronic fatigue syndrome. Clin Infect Dis 1999; 29:452-453. 133.Machtey I. Chlamydia pneumoniae antibodies in myalgia of unknown cause (including fibromyalgia) Br J Rheumatol 1997; 36:1134. 134.Kanauchi M, Kawano T, Dohi K. Association of Chlamydia pneumoniae infection with diabetic nephropathy. Diabetes Res Clin Pract 2000; 47:45-48. 135.Hatch TP. Metabolism of Chlamydia. CRC Press, Boca Raton, 1988. 136.Iliffe-Lee ER, McClarty G. Glucose metabolism in Chlamydia trachomatis: the “energy parasite” hypothesis revis- ited. Mol Microbiol 1999; 33:177-187. 137.Moulder JW. Glucose metabolism of Lcell before and after infection with Chlamydia. 1970; J Bacteriol 104:1189-1196. 138.Ojcius DM, Degani H, Mispelter J, Dautry-Varsat A. Enhancement of ATP levels and glucose metabolism during an infection by Chlamydia. J Biol Chem 1998; 278:7052-7058. 139.Vannucci SA, WM, Stratton CW, King LE. Pyoderma gangrenosum and Chlamydia pneumoniaeinfection in a diabetic man: pathogenic role or coincidence? J Am Acad Dermatol 2000; 42:295-297. 140.King LE Jr, Bushman T, Stratton CW, WM. Diabetic foot ulcers and Chlamydia pneumoniae: innocent bystander or opportunistic pathogen? Arch Dermatol (in press). 141.Alberts GL, Stratton CW, WM, e JJ. Potential role of Chlamydia pneumoniaein the patho- genesis or interstitial cystitis. Presented at the Annual Meeting of the Society for Urodynamics and Female Urology in Anaheim, CA, June 2001. Quote Link to comment Share on other sites More sharing options...
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