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