Infection and Chronic Diseases - Part 2


Our Chronic Disease Support video on chronic infection and chronic diseases (Part 2) is now available on our youtube channel.


https://youtu.be/N7P47QyAB3o

Here is the introduction from the paper above by Dr. Gail Cassell from Eli Lilly:



The belief that infectious agents are a cause of chronic inflammatory diseases of unknown etiology and of cancer is not new. Approximately 100 years ago, doctors noted a connection between cervical cancer and sexual promiscuity that transcended mere coincidence (1). By 1911, a connection between viruses and cancers in animals had become well established (2). As early as the 1930s, mycoplasmas were proposed as a cause of rheumatoid arthritis in humans, and shortly thereafter, they were proven to be the most common cause of naturally occurring chronic arthritis in animals (3). Proof of causality of cancer and arthritis in humans was more difficult. When searches for infectious agents in cancer and arthritis found none, research began to focus on mechanisms of inflammation, tumorogenesis, and drug discovery. More recently, however, scientists have renewed searches for infectious agents.


Advances in molecular biology and medical devices have revolutionized our ability to detect very low numbers of infectious agents in specimens collected directly from the affected site. HIV has demonstrated the ability of infectious agents to produce slowly progressive, chronic disease with a wide spectrum of clinical manifestations and disease outcomes. Increased understanding of the body's defense mechanisms and the demonstration that final outcome of infection is as much determined by the genetic background of the host as by the genetic makeup of the infecting agent suggest that a number of chronic diseases of unknown etiology may be caused by an infectious agent.

Recent data suggest a role for one or more infectious agents in the following chronic diseases: chronic lung diseases (including asthma), cardiovascular disease, and cancer. Many of the agents implicated are commonly transmissible and are either treatable with existing antibiotics or are potentially treatable with antiviral drugs. Thus, proof of causality in any one of these diseases would have enormous implications for public health, treatment, and prevention. Few areas of research hold greater promise of contributing to our understanding of infectious diseases and the eventual relief of human suffering.


The intent of this paper is not to provide a comprehensive review of chronic inflammatory diseases of unknown etiology and the agents implicated but rather to utilize several models to discuss available data and to illustrate the difficulty in proving causality in chronic inflammatory diseases. The discussion is based upon the following assumptions. Most chronic inflammatory diseases are likely multifactorial. Heredity, environment, and nutrition are critical determinants of disease expression with heredity being the most important.


Theoretically, chronic inflammatory diseases currently of unknown etiology could result from three different types of pathogens: 1) those that are fastidious and previously recognized but because of their fastidiousness or lack of appreciation of their disease-producing potential are not included in the differential diagnosis, and 2) infectious agents previously not recognized that therefore go undetected. Infection with either group can result in misdiagnosis and lack of treatment. Depending upon the biology of the organism and intrinsic and extrinsic factors of the host the organism can persist, resulting in chronic inflammation. The third group of pathogens would be those that elicit an autoimmune response resulting in persistent inflammation without the persistence of the inciting agent. Examples of the first two groups of pathogens will be discussed here using mycoplasmas to typify the first group and Chlamydia pneumoniae the second. Finally, recent advances in our understanding of the role of infectious agents in cancer will also be summarized.


References


  1. Moscicki AB, Palefsky J, Gonzales J, Schoolnik GK. Human papillomavirus infection in sexually active adolescent females: prevalence and risk factors. Pediatr Res. 1990;28:507–13. DOIExternal LinkPubMedExternal Link

  2. Rous P. Transmission of a malignant new growth by means of a cell-free filtrate. JAMA. 1911;56:198.

  3. Cassell GH, Cole BC. Mycoplasmas as agents of human disease. N Engl J Med. 1981;304:80–9.PubMedExternal Link

  4. Lindsey JR, Baker HJ, Overcash RG, Cassell GH, Hunt CE. Murine chronic respiratory disease: significance as a research complication and experimental production with Mycoplasma pulmonis. Am J Pathol. 1971;64:675–708.PubMedExternal Link

  5. Hektoen L. Observations on pulmonary infections in rats. Transactions of the Chicago Pathology Society 1015-1918;10:105-8.

  6. Nelson JB. Infectious catarrh of the albino rat. I. Experimental transmission in relation to the role of Actinobacillus muris. II. The causal relation of cocobacilliform bodies. J Exp Med. 1940;72:645–54, 666–7. DOIExternal LinkPubMedExternal Link

  7. Cassell GH, Lindsey JR, Baker HJ. Mycoplasmal and rickettsial diseases. In: Baker HJ, Lindsey JR, Weisbroth SH, editors. The laboratory rat, Vol. I. New York: Academic Press; 1979. p. 243-69.

  8. Cassell GH, Lindsey JR, Overcash RG, Baker HJ. Murine mycoplasma respiratory disease. Ann N Y Acad Sci. 1973;225:395–412. DOIExternal Link

  9. Davis JK, Parker RF, White H, Dziedzic D, Taylor G, Davidson MK, Strain differences in susceptibility to murine respiratory mycoplasmosis in C57BL/6 and C3H/HeN mice. Infect Immun. 1985;50:647–54.PubMedExternal Link

  10. Davis JK, Thorp RB, Maddox PA, Brown MB, Cassell GH. Murine respiratory mycoplasmosis in F344 and LEW rats: evolution of lesions and lung lymphoid cell populations. Infect Immun. 1982;36:720–9.PubMedExternal Link

  11. Cartner SC, Simecka JW, Briles DE, Cassell GH, Lindsey JR. Resistance to mycoplasmal lung disease in mice is a complex genetic trait. Infect Immun. 1996;64:5326–31.PubMedExternal Link

  12. Simecka JW, Davis JK, Davidson MK, Ross SE, Städtlaender CTK-H, Cassell GH. Mycoplasma diseases of animals. In: Maniloff J, McElhaney R, Finch L, Baseman J, editors. Mycoplasmas: molecular biology and pathogenesis. Washington: American Society of Microbiology; 1992. p. 391-415.

  13. Ross SF, Simecka JW, Gambill GP, Davis JK, Cassell GH. Mycoplasma pulmonis possesses a novel chemattractant for B lymphocytes. Infect Immun. 1992;60:669–74.PubMedExternal Link

  14. O'Brodovich HM, Mellins RB. Bronchopulmonary dysplasia. Unresolved neonatal acute lung injury. Am Rev Respir Dis. 1985;132:694–709.PubMedExternal Link

  15. Saigal S, Rosenbaum P, Stoskopf B, Sinclair JC. Outcome in infants 501-1000 gm birth weight delivered to residents of the McMaster Health Region. J Pediatr. 1984;105:969–76. DOIExternal LinkPubMedExternal Link

  16. Naeye RL, Dellinger WS, Blanc WA. Fetal and maternal features of antenatal bacterial infections. J Pediatr. 1971;79:733–9. DOIExternal LinkPubMedExternal Link

  17. Dennehy PH. Respiratory infections in the newborn. Clin Perinatol. 1987;14:667–82.PubMedExternal Link

  18. Tafari N, Ross S, Naeye RL. Mycoplasma 'T' strains and perinatal death. Lancet. 1976;1:108–9. DOIExternal LinkPubMedExternal Link

  19. Cassell GH, Waites KB, Crouse DT, Rudd PT, Canupp KC, Stagno S, Association of Ureaplasma urealyticum infection of the lower respiratory tract with chronic lung disease and death in very-low-birthweight infants. Lancet. 1988;2:240–5. DOIExternal LinkPubMedExternal Link

  20. Quinn PA, Gillan JE, Markestad T, St. John MA, Daneman A, Lie KI, Intrauterine infection with Ureaplasma urealyticum as a cause of fatal neonatal pneumonia. Pediatr Infect Dis. 1985;4:538–43.PubMedExternal Link

  21. Gray DJ, Robinson HB, Malone J. Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum. Prenat Diagn. 1992;12:111–7. DOIExternal LinkPubMedExternal Link

  22. Waites KB, Crouse DT, Philips JB III, Canupp KC, Cassell GH. Ureaplasmal pneumonia and sepsis associated with persistent pulmonary hypertension of the newborn. Pediatrics. 1989;83:79–85.PubMedExternal Link

  23. Brus F, van Waarde WM, Schoots C, Oetomo SB. Fetal ureaplasmal pneumonia and sepsis in a newborn infant. Eur J Pediatr. 1991;150:782–3. DOIExternal LinkPubMedExternal Link

  24. Cassell GH, Waites KB, Gibbs RS, Davis JK. The role of Ureaplasma urealyticum in amnionitis. Pediatr Infect Dis. 1986;5:S247–52.PubMedExternal Link

  25. Rudd PT, Carrington D. A prospective study of chlamydial, mycoplasmal and viral infections in a neonatal intensive care unit. Arch Dis Child. 1985;59:120–5. DOIExternal Link

  26. Taylor-Robinson D, Furr PM, Liberman MM. The occurrence of genital mycoplasmas in babies with and without respiratory diseases. Acta Paediatr Scand. 1984;73:383–1984. DOIExternal LinkPubMedExternal Link

  27. Ollikainen J, Heikkaniemi H, Korppi M, Sarkkinen H, Heinonen K. Ureaplasma urealyticum infection associated with acute respiratory insufficiency and death in premature infants. J Pediatr. 1993;122:756–60. DOIExternal LinkPubMedExternal Link

  28. Rudd PT, Cassell GH, Waites KB, Davis JK, Duffy LB. Ureaplasma urealyticum pneumonia: experimental production and demonstration of age-related susceptibility. Infect Immun. 1989;57:918–25.PubMedExternal Link

  29. Walsh WF, Butler J, Coalson J, Hensley D, Cassell GH, Delemos RA. A primate model of Ureaplasma urealyticum infection in the premature infant with hyaline membrane disease. Clin Infect Dis. 1993;17:S158–62.PubMedExternal Link

  30. Crouse DT, Odrezin GT, Cutter GR, Reese JM, Hamrick WB, Waites KB, Radiographic changes associated with tracheal isolation of Ureaplasma urealyticum from neonates. Clin Infect Dis. 1993;17:S122–30.PubMedExternal Link

  31. Sidiropoulos D, Herrmann U, Morell A. Transplacental passage of intravenous immunoglobulin in the last trimester of pregnancy. J Pediatr. 1986;109:505–8. DOIExternal LinkPubMedExternal Link

  32. Cassell GH. The pathogenic potential of mycoplasmas: Mycoplasma pulmonis as a model. Derrick Edward Award Lecture. Rev Infect Dis. 1982;4:S18–34.PubMedExternal Link

  33. Cassell GH, Waites KB, Crouse DT. Mycoplasmal infections. In: Remington JS, Klein JO, editors. Infectious diseases of the fetus and newborn infant. Philadelphia (PA): W.B. Saunders Co.; 1994. p. 619-55.

  34. Dyke MP, Grauaug A, Kohan R, Ott K, Andrews R. Ureaplasma urealyticum in a neonatal intensive care population. J Paediatr Child Health. 1993;29:295–7. DOIExternal LinkPubMedExternal Link

  35. Saxen H, Hakkarainen K, Pohjavuori M. Chronic lung disease of preterm infants in Finland is not associated with Ureaplasma urealyticum colonization. Acta Paediatr. 1993;82:198–201. DOIExternal LinkPubMedExternal Link

  36. Valencia GB, Banzon F, Cummings M. Mycoplasma hominis and Ureaplasma urealyticum in neonates with suspected infection. Pediatr Infect Dis J. 1993;12:571–3. DOIExternal LinkPubMedExternal Link

  37. Crouse DT, Cassell GH, Waites KB, Foster JM, Cassady G. Hyperoxia potentiates Ureaplasma urealyticum pneumonia in newborn mice. Infect Immun. 1990;58:3487–93.PubMedExternal Link

  38. Stancombe BB, Walsh WF, Derdak S, Dixon P, Hensley D. Induction of human neonatal pulmonary fibroblast cytokines by hyperoxia and Ureaplasma urealyticum. Clin Infect Dis. 1993;17:S154–7.PubMedExternal Link

  39. Payne NR, Steinberg S, Ackerman P, Cheenka BA, Sane SM, Anderson KT, New prospective studies of the association of Ureaplasma urealyticum colonization and chronic lung disease. Clin Infect Dis. 1993;17:S117–21.PubMedExternal Link

  40. Cassell GH, Davis RO, Waites KB, Brown MB, Marriott PA, Stagno S, Isolation of Mycoplasma hominis and Ureaplasma urealyticum from amniotic fluid at 16-20 weeks gestation: potential effect on outcome of pregnancy. Sex Transm Dis. 1983;10:294–302.PubMedExternal Link

  41. Parker RF, Davis JK, Cassell GH, White H, Dziedzic D, Blalock DK, Short-term exposure to nitrogen dioxide enhances susceptibility to murine respiratory myco-plasmosis and decreases intrapulmonary killing of Mycoplasma pulmonis. Am Rev Respir Dis. 1989;140:502–12.PubMedExternal Link

  42. National Heart. Lung and Blood Institute Data Fact Sheet, Asthma Statistics, May, 1992. Washington: National Institutes of Health; 1992.

  43. Rao M, Kravath R, Abadco D, Arden J, Steiner P. Childhood asthma mortality: the Brooklyn experience and a brief review. J Assoc Acad Minor Phys. 1991;2:127–30.PubMedExternal Link

  44. Sterk PJ. Virus-induced airway hyperresponsiveness in man. Eur Respir J. 1993;6:894–902.PubMedExternal Link

  45. Cassell GH, Clyde WA, Davis JK. Mycoplasmal res-piratory infections. In: Razin S, Tully JG, editors. The Mycoplasmas. New York: Academic Press; 1985. p. 66-106.

  46. Shimuzu T, Mochizuki H, Kato M, Shjigeta M, Morikawa A, Hori T. Immunoglobulin levels, number of eosinophils in the peripheral blood and bronchial hypersensitivity in children with Mycoplasma pneumoniae pneumonia. Japanese Journal of Allergology. 1991;40:21–7.PubMedExternal Link

  47. Sabato AR, Martin AJ, Marmion BP, Kok TW, Cooper DM. Mycoplasma pneumoniae: acute illness, antibiotics, and subsequent pulmonary function. Arch Dis Child. 1984;59:1034–7. DOIExternal LinkPubMedExternal Link

  48. Seggev JS, Lis I, Siman-Tov S, Gutman R, Abu-Samara H, Bouchey H, Mycoplasma pneumoniae is a frequent cause of exacerbation of bronchial asthma in adults. Ann Allergy. 1986;57:263–5.PubMedExternal Link

  49. Yano T, Ichikawa Y, Komatu S, Arai S, Oizumi K. Association of Mycoplasma pneumoniae antigen with initial onset of bronchial asthma. Am J Respir Crit Care Med. 1994;149:1348–53.PubMedExternal Link

  50. Henderson FW, Clyde WA Jr, Collier AM, Denny FW, Senior RJ, Sheaffer CI, The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice. J Pediatr. 1979;95:183–90. DOIExternal LinkPubMedExternal Link

  51. Grayston JT. Infections caused by Chlamydia pneumoniae strain TWAR. Clin Infect Dis. 1992;15:757–63.PubMedExternal Link

  52. Hahn DL, Dodge RW, Golubjatnikov R. Association of Chlamydia pneumoniae (TWAR) infection with wheezing, asthmatic bronchitis and adult-onset asthma. JAMA. 1991;266:225–30. DOIExternal LinkPubMedExternal Link

  53. Emre U, Roblin PM, Gelling M, Dumornay W, Rao M, Hammerschlag MR, The association of Chlamydia pneumoniae infection and reactive airway disease in children. Archives of Pediatric Medicine. 1994;148:727–32.

  54. Hammerschlag MR, Chirgwin K, Roblin PM. Persistent infection with Chlamydia pneumoniae following acute respiratory illness. Clin Infect Dis. 1992;14:178–222.PubMedExternal Link

  55. Kraft M, Cassell GH, Henson JE, Watson H, Williamson J, Marmion BP, Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma. Am J Respir Crit Care Med. 1998. In press.PubMedExternal Link

  56. Allegra L, Blasi F, Centanni S, Cosentini R, Denti F, Raccanelli R, Acute exacerbations of asthma in adults: role of Chlamydia pneumoniae infection. Eur Respir J. 1994;7:2165–8. DOIExternal LinkPubMedExternal Link

  57. Hahn DL, Golubjatnikov R. Asthma and Chlamydial infection: a case series. J Fam Pract. 1994;38:589–95.PubMedExternal Link

  58. Block S, Hedrick J, Hammerschlag AR, Craft JC. Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric community-acquired pneumonia: comparative safety and efficacy of clarithromycin vs. erythromycin. Pediatr Infect Dis. 1995;14:471–7.

  59. Harris JAS, Kolokathis A, Campbell M, Cassell GH, Hammerschlag MR. Safety and efficacy of azithromycin treatment of community acquired pneumonia in children. Pediatr Infect Dis J. 1998. In press.

  60. Giron JA, Lange M, Baseman JB. Adherence, fibronectin, binding, and induction of cytoskeleton reorganization in cultured human cells by Mycoplasma penetrans. Infect Immun. 1996;64:197–208.PubMedExternal Link

  61. Wise KS, Cassell GH, Acton RT. Selective association of murine T lymphoblastoid cell surface alloantigens with Mycoplasma hyorhinis. Proc Natl Acad Sci U S A. 1978;75:4479–83. DOIExternal LinkPubMedExternal Link

  62. Marmion BP, Williamson J, Worswick PA, Kok TW, Harris RJ. Experience with newer techniques for the laboratory detection of Mycoplasma pneumoniae infection: Adelaide, 1978-1991. Clin Infect Dis. 1993;17:S90–9.PubMedExternal Link

  63. Cassell GH, Drnec J, Waites KB, Pate MS, Duffy LB, Watson HL, Efficacy of clarithromycin against Mycoplasma pneumoniae. J Antimicrob Chemother. 1991;27:47–59.PubMedExternal Link

  64. Gray GC, Duffy LB, Paver RJ, Putnam SD, Reynolds RJ, Cassell GH. Mycoplasma pneumoniae: a frequent cause of pneumonia among U.S. marines in southern California. Mil Med. 1997;162:524–6.PubMedExternal Link

  65. Osler W. Diseases of the arteries. In: Osler W, editor. Modern medicine: its practice and theory. Philadelphia (PA): Lea & Febiger; 1908. p. 429-47.

  66. Fabricant CG, Fabricant J, Litrenta MM, Minick CR. Virus-induced atherosclerosis. J Exp Med. 1978;:335–40. DOIExternal LinkPubMedExternal Link

  67. Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link? Lancet. 1997;350:430–6. DOIExternal LinkPubMedExternal Link

  68. Patel P, Mendall MA, Carrington D, Strachan DP, Leatham E, Molineaux N, Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. BMJ. 1995;311:711–4.PubMedExternal Link

  69. Melnick JL, Adam E, Debakey ME. Cytomegalovirus and atherosclerosis. Eur Heart J. 1993;14:30–8.PubMedExternal Link

  70. Beck J, Garcia R, Heiss G, Vokonas PS, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol. 1996;67:1123–37.PubMedExternal Link

  71. File TM, Bartlett JG, Cassell GH, Gaydos CA, Grayston JT, Hammerschlag MR, The importance of Chlamydia pneumoniae as a pathogen: the 1996 consensus conference on Chlamydia pneumoniae infections. Infect Dis Clin Pract. 1997;6:S28–31. DOIExternal Link

  72. Kuo C, Shor A, Campbell L, Fukushi H, Patton DL, Grayston JT. Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. J Infect Dis. 1993;167:841–9.PubMedExternal Link

  73. Kuo CC, Grayston JT, Campbell LA, Goo YA, Wissler RW, Benditt EP. Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years old). Proc Natl Acad Sci U S A. 1995;92:6911–4. DOIExternal LinkPubMedExternal Link

  74. Campbell LA, O'Brien ER, Capuccio AL, Kuo C-C, Wang S-P, Stewart D. Detection of Chlamydia pneumoniae TWAR in human coronary arterectomy tissues. J Infect Dis. 1995;172:585–8.PubMedExternal Link

  75. Ong G, Thomas BJ, Mansfield AO, Davidson BR, Taylor-Robinson D. Detection and widespread distribution of Chlamydia pneumoniae in the vascular system and its possible implications. J Clin Pathol. 1996;49:102–6. DOIExternal LinkPubMedExternal Link

  76. Jackson LA, Lee AC. Cho-Chou Kuo, Rodriquez DI, Lee A, Grayston JT. Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen. J Infect Dis. 1997;176:292–5. DOIExternal LinkPubMedExternal Link

  77. Blasi F, Denti F, Erba M. Detection of Chlamydia pneumoniae but not Helicobacter pylori in atherosclerotic plaques of aortic aneurysms. J Clin Microbiol. 1996;34:2766–9.PubMedExternal Link

  78. Muhlestein JB, Hammond EH, Carlquist JF, Radicke E, Thomson MJ, Karagounis LA, Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic versus other forms of cardiovascular disease. J Am Coll Cardiol. 1996;27:1555–61. DOIExternal LinkPubMedExternal Link

  79. Kuo CC, Jackson LA, Campbell LA, Grayston JT. Chlamydia pneumoniae (TWAR). Clin Microbiol Rev. 1995;8:451–61.PubMedExternal Link

  80. Yang ZP, Kuo CC, Grayston JT. Systemic dissemination of Chlamydia pneumoniae following intranasal inoculation in mice. J Infect Dis. 1995;171:736–8.PubMedExternal Link

  81. Fong IW, Chiu B, Viira E, Fong MW, Jang D, Mahony J. Rabbit model for Chlamydia pneumoniae infection. J Clin Microbiol. 1997;35:48–52.PubMedExternal Link

  82. Laitinen K, Laurila A, Pyhala L, Leinonen M, Saikku P. Chlamydia pneumoniae infection induces inflammatory changes in the aortas of rabbits. Infect Immun. 1997;65:4832–5.PubMedExternal Link

  83. Kaukoranta-Tolvanen SS, Teppo AM, Laitinen K, Linnavuori K, Leinonen M. Growth of Chlamydia pneumoniae in cultured human peripheral blood mononuclear cells and induction of a cytokine response. Microb Pathog. 1996;21:215–21. DOIExternal LinkPubMedExternal Link

  84. Molestina R, Miller RD, Summersgill JT. Ramirez. Chlamydia pneumoniae stimulates secretion of chemokines and adhesion molecules in human endothelial cells. In: Abstracts of the 96th General Meeting of the American Society for Microbiology 1996. Washington: American Society for Microbiology; 1996. Abstract No. 243.

  85. Nurminen M, Leinonen M, Saikku P, Makela PH. The genus-specific antigen of Chlamydia: resemblance to the lipopolysaccharide of enteric bacteria. Science. 1988;220:1279–81. DOIExternal Link

  86. Saikku P, Leinonen M, Tenkanen L, Linnanmaki E, Ekman MR, Manninen V, Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki heart study. Ann Intern Med. 1992;116:273–8.PubMedExternal Link

  87. Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm J. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation. 1997;96:404–7.PubMedExternal Link

  88. Gurfinkel E, Bozovich G, Daroca A, Beck E, Mautner B; ROXIS Study Group. Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study. Lancet. 1997;350:404–7. DOIExternal LinkPubMedExternal Link

  89. Liddy P, Egan D, Skarlartos S. Roles of infectious agents in atherosclerosis and restenosis. Circulation. 1997;96:4095–103.PubMedExternal Link

  90. Kadota JL. Non antibiotic effects of antibiotics. J Clin Micro Infect. 1996;1:220–2.

  91. Labro MT. Intracellular bioactivity of macrolides [suppl]. J Clin Micro Infect. 1996;1:24–30. DOIExternal Link

  92. Agen C, Danesi R, Blandizzi C. Macrolide antibiotics as antiinflammatory agents:roxithromycin in an unexpected role. Agents Actions. 1993;38:85–90. DOIExternal LinkPubMedExternal Link

  93. Kita E, Sawaki M, Mikasa K. Alterations of host response by long term treatment of roxithromycin. J Antimicrob Chemother. 1993;32:285–94. DOIExternal LinkPubMedExternal Link

  94. Pisani P, Parkin DM. Munoz, Ferlay J. Cancer and infection: Estimates of the attributable fraction in 1990. Cancer Epidemiol Biomarkers Prev. 1997;6:387–400.PubMedExternal Link

  95. Infectious diseases and cancer. 1996. In: The World Health Report 1996. Fighting disease fostering development. Geneva: World Health Organization; 1996. p. 59-62.

  96. Parsonnet J. Helicobacter pylori. Infect Dis Clin North Am. 1998;12:185–97. DOIExternal LinkPubMedExternal Link

  97. Marshall BJ. History of the discovery of C. pylori. In Blaser MJ, editor. Campylobacter pylori in gastritis and peptic ulcer disease. New York: Igaku-Shoin; 1989. p. 7-23.

  98. Moller H, Heseltine E. Vaqinio. Working group report on schistosomes, liver flukes, and Helicobacter pylori. Int J Cancer. 1995;60:587–9. DOIExternal LinkPubMedExternal Link

  99. NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. JAMA. 1994;272:65–9. DOIExternal LinkPubMedExternal Link

  100. Xiang Z, Censini S, Bayeli PF, Telford JL, Figura N, Rappuoli R, Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin. Infect Immun. 1995;63:94–8.PubMedExternal Link

  101. Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995;55:2111–5.PubMedExternal Link

  102. Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, Liang DC, Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med. 1997;336:1855–9. DOIExternal LinkPubMedExternal Link

  103. Hepatitis viruses. Monographs on the evaluation of carcinogenic risks to humans. Lyon, France: IARC; 1994. IARC Scientific Publ No. 59.

  104. Chuang WL, Chang WY, Lu SN, Su WP, Lin ZY, Chen SC, The role of hepatitis B and C viruses in hepatocellular carcinoma in a hepatitis B endemic area. A case-control study. Cancer. 1992;69:2052–4. DOIExternal LinkPubMedExternal Link

  105. Human papillomaviruses. Monographs on the evaluation of carcinogenic risks to humans. Lyon, France: IARC; 1995. IARC Scientific Publ No. 64.

  106. Vousden KH, Farrel PJ. Viruses and human cancer. Br Med Bull. 1994;3:580–1.

  107. Morris JDH, Eddleston ALWF, Crook T. Viral infection and cancer. Lancet. 1995;346:754–8. DOIExternal LinkPubMedExternal Link

  108. Ohshima H, Bartsch H. Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat Res. 1994;305:253–64. DOIExternal LinkPubMedExternal Link

  109. Mackowiak PA. Microbial latency. Rev Infect Dis. 1984;6:649–67.PubMedExternal Link

  110. Pincus T. Rheumatoid arthritis: disappointing long-term outcomes despite successful short-term clinical trials. J Clin Epidemiol. 1988;41:1037. DOIExternal LinkPubMedExternal Link

  111. Feinstein AR. An additional basic science for clinical medicine: II. The limitations of randomized trials. Ann Intern Med. 1983;:544.PubMedExternal Link



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