Mycoplasmal and other chronic bacteria

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Infectious Disease Research Chronic Infectious Diseases Prof. Garth L. Nicolson Respiratory Diseases Chronic respiratory diseases, such as chronic asthma, airwayinflammation, chronic pneumonia and other respiratory diseases, are known tobe associated with chronic infections. For example, mycoplasmal infectionsare a common cause of upper respiratory infections, and severe asthma iscommonly associated with mycoplasmal infections. These are complex diseasesof largely unknown etiology, but in many cases chronic infections are toblame. Some infections, such as those caused by certain Mycoplasma andChlaymdia species that are invasive and are found in respiratory epithelialcells are able to suppress immune responses by suppressing the ability ofpulmonary macrophages to ingest and kill these infectious agents. Althoughwe do not know exactly what causes respiratory diseases, there is increasingevidence that in many patients chronic infections, particularly by certainbacteria and viruses, play an important role in these diseases along withgenetic predisposition and immune dysfunction. Although mycoplasmal infections are often associated with ChronicAsthma, the exact role of mycoplasmas in the pathogenesis of Asthma remainsunclear. Certain Mycoplasma species are involved in respiratory tractinfections associated with airway inflammations, induction of bronchialhyperresponsiveness (BHR) and asthmatic attacks. At a minimum, M. pneumoniaeinfections can cause worsening of conditions in asthmatic patients, whoseattacks are associated with significant and specific immune responses.Mycoplasmas are only one of many agents that can trigger BHR, and otherinfectious or chemical agents may contribute to the complex disease process.Such infectious agents could be involved in helping to cause the illness, orthey can affect patients by serving as cofactors for the illness (notcausing illness on their own but serving as important factors in the diseaseprocess) or even as opportunistic infections that increase patient morbidity(sickness) and complications associated with the disease (see Nicolson etal., Antimicrobics and Infectious Diseases Newsletter, 1999 ; 17(11):81-88). Urogenital Diseases We and others have found that Mycoplasma species are commonly presentin urogenital infections. For example, mycoplasmal infections were detectedin more than 12% of females who presented at gynecological services, andthey are associated with acute and nonspecific non-gonococcal urethritis inmales but not in asymptomatic controls. This type of microorganism is also acommon cause of genital infections in women, and it was detectable in 7% ofwomen with sexually transmitted diseases. Mycoplasmal and other chronicbacteria have been implicated in a wide variety of urogenital diseases, suchas pelvic inflammatory disease, infertility, non-gonococcal urethritis (NGU)and other genital infections, pyelonephritis, Reiter's syndrome, andperitonitis. The appearance of various bacterial species in bacterialvaginosis may be a result of pathophysiological alterations of the vaginalecosystem, and mycoplasmas appear to play an important role in this process.Mycoplasmas are also known to interfere in pregnancy and are thought to beinvolved in at least 11% of patients with fertility problems. Immunosuppressive Diseases Some Mycoplasma species, M. fermentans, M. penetrans, and M. pirum,have been implicated as infectious cofactors in HIV-AIDS. Using relativelyinsensitive techniques all three mycoplasmas have been detected in up to 20%of patients with HIV infections, and serological studies have suggested thatthe presence of M. penetrans is also associated with HIV infection.Moreover, the incidence of systemic mycoplasmal infections in HIV-AIDSpatients is probably much, much higher than previously thought and mayapproach 80% or more. Most of the older analyses were performed usingrelatively insensitive techniques, such as serological analysis. PathogenicMycoplasma species may influence HIV pathogenesis by specific and directactivation or suppression of the immune system, the production ofsuperantigens with subsequent alterations in immune responses, or by theircontribution to the oxidative stress observed in HIV-positive patients.Also, the development of AIDS may increase the susceptibility ofHIV-infected patients for coinfection with various Mycoplasma species, suchas M. fermentans. This species is able to bind HIV capsid protein gp120permitting adhesion of HIV virions to the mycoplasma surface. Subsequentlythe HIV viruses could be transported directly to cells expressing specificreceptors. After binding to target cells, mycoplasmas can stimulate hostcell activation by releasing certain cytokine mediators, which are knowneffectors for virus reproduction. Antigen similarities between the surface components of mycoplasmas andHIV-1 have led to speculation that they use similar mechanisms for cellentry. For example, the HIV-1 gp120 envelope glycoprotein and M. genitaliumadhesion proteins share protein sequence homology and also have significantsimilarity with the binding site proteins. The interactions ofmicroorganisms with certain antigens on host cells could contribute to anumber of possible outcomes, including immune cell dysfunction, depletion,cell shift (to other subsets of immune cells), antibody-producing immunecell proliferation, hyperglobulinemia (a state where certain immunoglobulinproteins of the same class are overproduced) and antigen-presenting celldysfunction (antigen presentation to the immune system is a very importantstep in immunity). Interestingly, all of these have been observed during thedevelopment of HIV-AIDS, and this makes certain microorganisms likemycoplasmas so important to understand this disease process. Cardiac Diseases Mycoplasmal and chlamydial infections of the heart have been reportedin patients with different types of carditis or heart infections. The mostcommon association was with M. pneumoniae or C. pneumoniae infection.Endocarditis and myocarditis associated with mycoplasmal and chlamydialinfections appear to be an important cause of death. Direct bacterialinvasion of M. pneumoniae into pericardial tissue appears to be more likelyto cause pericarditis than autoimmune phenomena. Viral and bacterial(Mycoplasma, Chlamydia and Mycobacterium tuberculosis) infections appear tobe common causes of myocarditis and/or pericarditis (infections of themuscle and cell lining of the heart), and this is just beginning to beappreciated by infectious disease specialists. PUBLICATIONS 1 The Pathogenesis And Treatment Of Mycoplasmal Infections Antimicrob. Infect. Dis. Newsl. 1999; 17(11) : 81-88 html doc 2 Role of Mycoplasmal Infections in Fatigue Illnesses: Chronic Fatigueand Fibromyalgia Syndromes, Gulf War Illness and Rheumatoid Arthritis The Clinical and Scientific Basis of CFS, Sydney, 1999 html doc 3 Mycoplasmal Infections in Chronic Illnesses: Fibromyalgia andChronic Fatigue Syndromes, Gulf War Illness, HIV-AIDS and RheumatoidArthritis Medical Sentinel 1999; 4:172-176 html doc 4 Identification And Treatment Of Chronic Infections In CFIDS,Fibromyalgia Syndrome And Rheumatoid Arthritis CFIDS Chronicle 1999; 12(3): 19-21 html doc 5 Diagnosis and integrative treatment of intracellular bacterialinfections in Chronic Fatigue and Fibromyalgia Syndromes, Gulf War Illness,Rheumatoid Arthritis and other chronic illnesses. Clin. Pract. Alt. Medicine2000;1(2): 92-102. html doc 6 Role of Mycoplasmal Infections in Fatigue Illnesses: Chronic Fatigueand Fibromyalgia Syndromes, Gulf War Illness and Rheumatoid Arthritis J.Chronic Fatigue Syndr. 2000; 6(3/4):23-39 html doc 7 Examination of mycoplasmas in blood of 565 Chronic Illness patientsby polymerase chain reaction. Intern. J. Med. Biol. Environ. 2000; 28(1):15-23. html doc 8 Bacterial and Viral Co-Infections in Chronic Fatigue Syndrome(CFS/ME) Patients, by Nicolson et al., Proc. Clinical & ScientificConference on Myalgic Encephalopathy/Chronic Fatigue Syndrome, thePractitioners Challenge, Alison Hunter Foundation, Sydney, Australia 2002html doc 9 Brucella Abortus Bang Its Relationship to Other Diseases, by A.J.Lindeman. Journal of Degenerative Diseases 2002 html doc 10 High prevalence of mycoplasmal infections among European ChronicFatigue Syndrome patients. Examination of four Mycoplasma species in ChronicFatigue Syndrome patients. FEMS Immunol. Med. Microbiol. 2002; 34: 209-214.html doc 11 Multiple Co-Infections (Mycoplasma, Chlamydia, Human HerpesVirus-6) in Blood of Chronic Fatigue Syndrome Patients. G.L. Nicolson etal., Journal of Chronic Fatigue Syndrome 2003; 11(2):7-19. html docback to the top REPORTS 1 Diagnosis and Therapy of Chronic Systemic Co-infections In LymeDisease and Other Tick-Borne Infectious Diseases html doc 2 Autoimmune Neurological and Rheumatic Diseases: Role of ChronicInfections in Morbitity and Progression by Garth Nicolson and NancyNicolson, Proc. 13th Intern. Symp. Integrative Medicine 2001; 13: 104-112.html doc 3 Mycoplasmas: the Missing Link in Fatiguing Illnesses by MichaelGuthrie, Alternative Medicine; 2001; Sept: 60-70. html doc 4 Veterinary Testing for Chronic Infections html doc 5 Recommendations for diagnostic laboratory testing html doc 6 Mycology News for Health Practitioners, Vol. 1, No. 6, Feb. 2002html doc 7 Chronic Co-Infections in Chronic Fatigue Syndrome, FibromyalgiaSyndrome and Other Chronic Illnesses by Garth Nicolson and Paul Berns, 2002.html doc