Archive for the 'Uncategorized' Category

Review Article: Are the Infectious Roots of Alzheimer’s Buried Deep in the Past?

February 26, 2017

Dr. Lawrence Broxmeyer, MD

LINK-OUT TO REVIEW ARTICLE -51778-ipjpe-3-s2-2

Citation: Broxmeyer L. Are the Infectious Roots
of Alzheimer’s Buried Deep in the Past? J Mol
Path Epidemol. 2017, 3:2.

Received: January 13, 2017; Accepted: February 20, 2017; Published: February 22,

© Under License of Creative Commons Attribution 3.0 License


Recent literature shows a controversial new push to tie microorganisms to Alzheimer’s disease (AD). Study after study, in which scientists have injected human Alzheimer-diseased brain tissue into mice and other laboratory animals that later developed the disease have left little doubt that Alzheimer’s disease (AD) arises from an infectious process. By 2013 Mawanda and Wallace’s “Can Infections Cause Alzheimer’s Disease” struck down some of the commonly entertained pathogens for AD such as herpes simplex virus type 1, Chlamydia pneumoniae, and several types of spirochetes. Instead they pointed to two prime suspects for Alzheimer’s amyloid-beta deposition: “especially chronic infections like tuberculosis and leprosy.” To be sure, it was German neuropathologist Oskar Fischer of the Prague school of Neuropathology, Alzheimer’s great rival, who was the first to suggest that infection might be causative for Alzheimer’s. Fischer’s credentials: he was the co-discoverer of Alzheimer’s disease. His suspected germ was the Streptothrix, today classified as an Actinomycetes, a rare central nervous system pathogen which at the time was so constantly and consistently mistaken for tuberculosis that Choppen-Jones suggested that TB be called tuberculomycosis. And Just ten years before Oskar Fischer found Actinomycosis-like forms in Alzheimer’s cerebral plaque, Babèş and immunologist Levaditi reported in “On the Actinomycotic Shape of the Tuberculous Bacilli” that Fischer’s typical Actinomyces-like clusters [Drüsen] with clubs appeared in the tissue of rabbits inoculated with tubercle bacilli beneath the dura mater of their brains. Investigators who supported and subsequenly followed up on Fischer’s Alzheimer’s germ are also discussed.

Keywords: Alzheimer’s disease, Infectious Cause of Alzheimer’s Disease, Oskar Fischer, Alois Alzheimer, Neurodegenerative Disease, Neurotuberculosis


  1. Itzhaki RF, Lathe R, Balin BJ, Ball MJ, Bearer EL, Braak H et al. Microbes and Alzheimer’s Disease. J Alzheimers Dis. 2016;51(4):979-84.
  2. Mawanda F, Wallace R. Can infections cause Alzheimer’s disease? Epidemiol Rev. 2013; 35:161-80.
  3. Itzhaki RF, Lin WR, Shang D, Wilcock GK, Faragher B, Jamieson GA. Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. Lancet. 1997 Jan 25;349(9047):241-44.
  4. Goldman JS, Hahn SE, Catania JW, LaRusse-Eckert S, Butson MB, Rumbaugh M et al. American College of Medical Genetics and the National Society of Genetic Counselors. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011; 13(6): 597-605.
  5. Mayeux R, Sanders AM, Shea S, Mirra S, Evans D, Roses AD, Hyman BT et al. Utility of the Apolipoprotein E Genotype in the Diagnosis of Alzheimer’s disease. NEJM. 1998; 338(8):506-511.
  6. Riviere GR, Riviere KH, Smith KS. Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer’s disease. Oral Microbiol Immunol. 2002;17(2):113–118.
  7. Goedert M. Oskar Fischer and the study of dementia. Brain. 2009 Apr; 132(4): 1102–1111.
  8. De Beer FC, Nel AE, Gie RP, Donald PR, Strachan AF. Serum amyloid A protein and C-reactive protein levels in pulmonary tuberculosis: relationship to amyloidosis. Thorax. 1984; 39(3):196–200.
  9. Looi LM, Jayalakshim P, Lim KJ, Rajagopalen K. An immunohistochemical and morphological study of amyloidosis complicating leprosy in Malaysian patients. Ann Acad Med Singapore. 1988; 17(4):573–578.
  10. Looi LM. The pattern of amyloidosis in Malaysia. Malays J Pathol. 1994; 16(1):11–13.
  11. Röcken C, Radun D, Glasbrenner B, Malfertheiner P, Roessner A. Generalized AA-amyloidosis in a 58-year-old Caucasian woman with an 18-month history of gastrointestinal tuberculosis. Virchows Arch. 1999; 434(1):95–100.
  12. Wangel AG, Wegelius O, Dyrting AE. A family study of leprosy: subcutaneous amyloid deposits and humoral immune responses. Int J Lepr Other Mycobact Dis. 1982; 50(1):47–55.
  13. Tank SJ, Chima RS, Shah V, et al. Renal amyloidosis following tuberculosis. Indian J Pediatr. 2000; 67(9):679–681.
  14. Urban BA, Fishman EK, Goldman SM,  Scott WW Jr, Jones B, Humphrey RL et al. CT evaluation of amyloidosis: spectrum of disease. Radiographics.1993; 13(6):1295–1308.
  15. Alzheimer A. “Uber Eigenartige Krankheitsfalle des Spateren Alters,” Zeit fur die Ges    Neur und Psych 1911; 4: 356–85.
  16. Barlow T. Tuberculous Meningitis in A System of Medicine by Many Writers, edited by Thomas Clifford Allbutt, New York:The Macmillan Company. 1899; 7:466–91.
  17. Ranke O. Beitrage zur Lehre von der Meningitis tuberculoa. Edited by Franz Nissl and Alois Alzheimer. Histologische und Histopathologische Arbeiten uber die Grosshirnrinde. Jena, Germany. Verlag Von Gustave Fischer. 1908; 252–347
  18. Alzheimer A, Forstl H, Levy R. An English translation of Alzheimer’s 1911 paper Uber Age), Hist of Psychia 1991. 2:71–101.
  19. Spielmeyer W. Alzheimer’s Lebenswenk. Zeit fur die Ges Neur und Psych. 1916; 22: 1–44.
  20. Dunn N, Mullee M, Perry VH, Holmes C. Association between Dementia and Infectious Disease: Evidence from a Case-Control Study. Alz Dis & Assoc Disord. April–June 2005. 19: 2: 91–4.
  21. Nee IE, Lipppa CF. Alzheimer’s Disease in Twenty-Two Twin Pairs—Thirteen-Year Follow-Up: Hormonal, Infectious, and Traumatic Factors.  Dement and Geriat Cognit Disord 1999; 10: 148–51.
  22. Alteri CJ, Xicahténcati-Cortes J, Hess S, Caballero-Olin G, Giron JA, Friedman RL. Mycobacterium Tuberculosis Produces Pili during Human Infection. Proc of the Nat Acad of Sci. 2007; 104:12:5145–50.
  23. Tukel C, Wilson RP, Nishimori JH, Pezeshki M, Chromy BA, Baumler AJ. Responses to Amyloids of Microbial and Host Origin Are Mediated through Toll-Like Receptor 2 Cell Host and Microbe. Cell Host Microb. July, 2009; 6: 45–53.
  24. Kidd M. Paired Helical Filaments in Electron Microscopy of Alzheimer’s Disease, Nature. 1963; 197: 192–93.
  25. Fischer O. Miliare Nekrosen Mit Drusigen Wucherungen der Neurofibrillen, eine Regelmassige Veranderung der Hirnrinde bei Seniler Demenz (Miliary Necrosis with Nodular Proliferation of the Neurofibrils: A Common Change of the Cerebral Cortex in Senile Dementia). Monatsschr f Psychiat Neurol 1907; 22: 361-372.
  26. Leonard JM, des Prez RM. Tuberculous Meningitis. Infect Dis Clin of Nor Amer Dec, 1990; 4: 4: 769–87.
  27. Chantemesse A, Ėtude Sur la Méningite Tuberculeuse de L’adulte: Les Formes Anormales en Particulier. These de Med de Paris. 1884.
  28. Blocq P, Babes V, Marinesco G. Atlas der Pathologischen Histologie des Nervensystems.  Berlin: Hirschwald, 1892.
  29. Vera HD, Rettger LF. Morphological Variation of the Tubercle Bacillus and Certain Recently Isolated Soil Acid Fasts, with Emphasis on Filterability. Journ of Bact June, 1940; 39:6: 659–87.
  30. Babes V, Levaditi C. On the Actinomycotic Shape of the Tuberculosis Bacilli (Sur la Forme Actinomycosique du Bacilli de la Tuberculosis). Arch. of Med. Exp. et D’anat. 1897; 9:6:1041-8.
  31. Blocq P, Marinescu G. Sur les Lesions et la Pathogenie de L’epilepsie Dite Essentielle, Sem Med 1892; 12:445–6.
  32. Giulianz D, Vaca K, Corpuz M. Brain Glia Release Factors with Opposing Actions upon Neuronal Survival, Journ of Neurosci 1993; 13: 29–37.
  33. Curto M, Reali C, Palmieri G, Scintu F, Schivo ML, Sogos V et al., Inhibition of Cytokines Expression in Human Microglia Infected with Virulent and Nonvirulent Mycobacteria. Neurochem Internat 2004; 44: 381–92.
  34. Rock RB, Gekker G, Hu S, Sheng WS, Cheeran M, Lokensgard JR et al. Role of Microglia in Central Nervous System Infections. Clin Microb Rev. 2004; 17: 942–64.
  35. Peterson PK, Gekker G, Hu S, Sheng WS, Anderson WR, Ulevitch RJ et al. CD14 Receptor-Mediated Uptake of Nonopsonized Mycobacterium Tuberculosis by Human Microglia, Infect and Immun. April, 1995; 63:4:1598–602.
  36. Green JA, Elkington PT, Pennington CJ, Roncaroli F, Dholakia S, Moores RC et al. Mycobacterium Tuberculosis Upregulates Microglial Matrix Metalloproteinase-1 and -3 Expression and Secretion via NF-kappaB- and Activator Protein-1-Dependent Monocyte Networks. Journ of Immunol June, 2010;184:11: 6492–503.
  37. Beltan E, Horgen L, Rastogi N. Secretion of Cytokines by Human Macrophages upon Infection by Pathogenic and Nonpathogenic Mycobacteria, Microbio and Pathol. 2000; 28: 313–8.
  38. Fischer O. Die Presbyophrene Demenz, Deren Anatomische Grundlage und Klinische Abgrenzung, Z. Ges. Neurol. Psychiat 1910. 3: 371–471.
  39. Marinesco G, Etude Anatomique et Clinique des Plaques Dites Seniles, 1er semestre Encephale. Paris. 1912; 105–132.
  40. Harbitz F, Grondahl NB, Actinomycosis in Norway: Studies in the Etiology, Modes of Infection, and Treatment, Amer J of Med Sci 1911; 142:386–95.
  41. Woodhead GS. Bacteria and Their Products. London and New York: Walter Scott, Ltd./Charles Scribner’s Sons.1895; 258
  42. Cope VZ. Actinomycosis: The Actinomyces and Some Common Errors about the Actinomyces and Actinomycosis. Postgrad Med. 1952; 28: 572–4.
  43. Bolton CF, Ashenhurst EM, Review Article: Actinomycosis of the Brain. Can Med Assoc Journ April, 1964; 90: 922–8.
  44. Ponfick E, Die Actinomykose des Menschen, Eine Neue Infectionskrankheit auf Vergleichend-Pathologischer und Experimenteller Grundlage Geschildert. Berlin: A. Hirschwald, 1882.
  45. Harz B. Actinomyces Bovis, ein Neuer Schimmel in den Geweben des Rindes: Deutsche Zeitschr. f. their. Med. und Vergl. Path. Zweites Supplementheft. 1870;125
  46. Corper HJ. Complement-Fixation in Tuberculosis. The J of Infect Dis September 1916; 19:3:315–21.
  47. Maurer K, Maurer U. Alzheimer’s disease: The Life of a Physician and the Career of a Disease Chichester, West Sussex: Columbia University Press. 2003.
  48. Bielschowsky M. Die Silberimpragnation der Achsenzylinder. Centralbl 1902; 21:578–84.
  49. Bielschowsky M. Die Silberimpragnation der Neurofibrillen. Centralbl 1903; 22: 997–1006.
  50. Perusini G. Uber Klinisch und Histologish Eigenartige Psychische Erkrankungen des Spateren Lebensalters, in Histologische und Histopathologische Arbeiten, edited by F. Nissl and A. Alzheimer. Jena, Germany: Verlag G. Fischer. 1909; 297–351.
  51. Darzins E. The Bacteriology of Tuberculosis. University of Minnesota Press. 1958; 488:187.
  52. Schneider A, Arau´jo GW, Trajkovic K, Herrmann MM, Merkler D, Mandelkow E et al. Hyperphosphorylation and Aggregation of Tau in Experimental Autoimmune Encephalomyelitis. The J of Biolog Chem Dec, 2004; 279;53: 55833–39.
  53. Harris JE, Fernandez-Vilaseca M, Elkington PTG, Horncastle DE, Graeber MB, Friedland JS et al. IFN Synergizes with IL-1to Up-Regulate MMP-9 Secretion in a Cellular Model of Central Nervous System Tuberculosis, The FASEB J Feb, 2007; 21: 356–65.
  54. Kusebauch U, Ortega C, Ollodart A, Rogers RS, Sherman DR, Moritz RL et al., Mycobacterium Tuberculosis Supports Protein Tyrosine Phosphorylation, Proc of the Nat Acad of Sci June, 2014; 111:25: 9265–70.
  55. Chow K, Ng D, Stokes R, Johnson P. Protein Tyrosine Phosphorylation in Mycobacterium Tuberculosis, FEMS Microbi Letters  December, 1994; 124:2: 203–7.
  56. Shapiro IP, Masliah E, Saitoh T. Altered Protein Tyrosine Phosphorylation in Alzheimer’s disease. J of Neurochem April, 1991; 56:4: 1154–62.
  57. Wang X.-X., Tan M.-S., Yu J.-T., Tan L. Matrix Metalloproteinases and Their Multiple Roles in Alzheimer’s Disease, BioMed Res Internat 2014,
  58. Lubarsch O. Zur Kenntnis der auf die Samenblaschen Amyloidablagerungen, Virch Arch Path Anat 1930; 274:139–145.
  59. Southard EE, Anatomical Findings in Senile Dementia: A Diagnostic Study Bearing Especially on the Group of Cerebral Atrophies. Amer J of Insan April, 1910; 66:4:673–708:701, 706.
  60. Southard EE, Solomon HC. Neurosypilis: Modern Systematic Diagnosis and Treatment—Presented in One Hundred and Thirty-Seven Case Histories 1917; Boston: W. M. Leonard. 496 pp.
  61. Southard EE. Nondementia Nonpraecox: Note on the Advantages to Mental Hygiene of Extirpating a Term in History of Psychiatry, Classic Text No. 72. Los Angeles, London, New Delhi: Sage Publications 2007; 18:4: 483–502.
  62. Southard EE, Jarrett MC. The Kingdom of Evils: Psychiatric Social Work Presented in One Hundred Case Histories Together with a Classification of Social Divisions of Evil. New York: Macmillan 1922; 298–9.
  63. Kraepelin E. Memoirs. Berlin and New York: Springer-Verlag. 1987; 270:136.
  64. Clouston TS, Unsoundness of Mind New York: E. F. Dutton and Co., 1911.
  65. Clouston TS. Illustrations of Phthisical Insanity. J of Ment Sci 1864; 50:220-229: 226.
  66. Clouston TS. Clinical Lectures on Mental Disease. London: J. & A. Churchill, 1883; 210.
  67. Sethi NK, Sethi PK, Torgovnick J, Arsura E. Central Nervous System Tuberculosis Masquerading as Primary Dementia: A Case Report, Neurologia i Neurochirurgia Polska. September-October 2011; 45:5:510–513.
  68. Carpenter EG. Determinate Factors in the Cause of Insanity, Jour of the Amer Med Assoc 1903 Jan 24; 60:4:240–44.
  69. Winslow F. On Obscure Diseases of the Brain and Disorders of the Mind: Their Incipient Symptoms, Pathology, Diagnosis, Treatment, and Prophylaxis. London: John Churchill Publishers. April 1860; 790 pp.
  70. Claisse P and Abrami A. Un Cas de Méningite Tuberculeus Terrninee par Guerison. Bull. et mém. soc. méd. d. hop. de Par.1905; 22:390–403.
  71. Marta M, Pomponi M. Il Ruolo di Perusini Nella Definizione del Morbo di Alzheimer, Kos. 1992; 77: 39–41.
  72. Braun B, Stadlober-Degwerth M, Kluemann H. Alzheimer–Perusini Disease: The One-Hundredth Anniversary of Gaetano Perusini’s Publication. Nervenarzt March 2011; 82:3: 363–66.
  73. Papavoine, LN Propositions Sur Les Tubercules Considérés Spécialement Chez le Enfans. Paris. 1830; 86:231.
  74. Rindfleisch R. Der Miliare Tuberkel. Virchow’s Arch. 1862; 24:571.
  75. Osler W, McCrae T. Modern Medicine: Its Theory and Practice, vol. V: Diseases of the Nervous System, 2nd edition. Philadelphia and New York: Lea & Febiger. 1915; 319.
  76. Guarnieri G. Note Istologiche Sulla Meningite Tubercolare.  Arch. Per le Scien. Med., Torino, 7th ed., 1883 1: 59–70.
  77. Hektoen L. The Vascular Changes of Tuberculous Meningitis, Especially with Tuberculous Endarteritis, J of Exper Med 1896; 1:112-163.
  78. Schwartz P. Amyloidosis—Cause and Manifestation of Senile Deterioration. Springfield, Illinois: Charles C Thomas. 1970; 363.
  79. Schwartz P. Amyloid Degeneration and Tuberculosis in the Aged. Gerontologia 1972; 18:5: 321–62.
  80. Hass GM, Huntington R. Amyloid 111: The Properties of Amyloid Deposits Occurring in Several Species under Diverse Conditions. Arch of Path 1943; 35: 226–41.
  81. Alzheimer A. Uber Eine Eigenartige Erkrankung des Zentralen Nervensystems Mit Bulbaen Symptomen und Schmerzhaften Spastischen Krampfzustanden der Extremitaen, Zeit fur die Gesamte Neurolog und Psychiat. 1916. 33: 45–59.
  82. Maurer K, Volk K, Gerbaldo S. Auguste D and Alzheimer’s disease, The Lancet May 1997; 349: 9064:1546–49.
  83. Jelliffe SE. Proceedings: National Association for the Study and Prevention of Tuberculosis, The Med News January-June, 1905; 86:1150 .
  84. Gerstenbrand F, Jellinger K, Maida E, Pilz A, Sandhofer F, and Weissenbacher G, Symptomatology of the Most Severe Form of Tuberculous Meningitis. J of Neurol 1980; 222:3:191–204.
  85. Kelynack TN. Tuberculosis in Infancy and Childhood. London: Bailliere, Tindall, and Cox. 1908.
  86. Rao VV, Gupta EV, Thomas IM. Chromosome Damage in Untreated Tuberculosis Patients. Tubercle September, 1990; 71:3:169-72.
  87. Wuerthele-Caspe V, Alexander-Jackson E, Gregory M, Smith LW, Diller IC, Mankowski Z. Intracellular Acid-Fast Microorganism: Isolated from Two Cases of Hepatolenticular Degeneration, J of the Amer Med Wom Assoc 1956 11:4:120–9.
  88. Jancovic J, Tolosa E. Parkinson’s Disease and Movement Disorders. Baltimore: Williams & Wilkins 1998; 205-16.
  89. Burn CG, Unidentified Gram-Positive Bacillus Associated with Meningo-Encephalitis, Proc of the Soc for Exper Biol and Med 1934; 31:1095.
  90. Livingston V, A Specific Type of Organism Cultivated from Malignancy: Bacterial and Proposed Classification. Ann of the New York Acad of Sci 1970; 174: 636–54.
  91. Bandelier B, Roepke O, Lehrbuch der Spezifischen Diagnostic und Therapie der Tuberkulose: fur arzte und Studierende Wurzburg: Curt Kabitzsch. 1911.
  92. Bandelier B, Roepke O. A Clinical System of Tuberculosis, translated from the Second German Edition by G. Band and Bertram Hunt, MD. New York: William Wood and Company. 1913.
  93. Nature Editorial, Forthcoming Books. March 13, 1913, Nature 91: 44.
  94. Millar BC, Moore JE, Emerging Issues in Infective Endocarditis, Emerg Infect Dis June, 2004; 10:6: 1110–6.
  95. Liu A, Nicol E, Hu Y, Coates A. Tuberculous Endocarditis, Internat J of Cardiol August, 2013; 167:3: 640–5.
  96. Gordon BL, Ocular Tuberculosis, Its Relation to General Tuberculosis—Ophthalmologic Reviews, edited by Francis Heed Adler. 1944; 541–56.
  97. Sands IJ, Senile and Presenile Psychosis, Neur Bulletin October 1918; 1:10: 377–385.


October 9, 2016





Recent literature shows a controversial new push to tie microorganisms to Alzheimer’s disease (AD) ― which despite the protests of some, is badly needed. Indeed there is a good chance that Alzheimer’s is caused by a microbe. Study after study, in which scientists have injected human Alzheimer-diseased brain tissue into mice and other laboratory animals that later developed the disease have left little doubt that Alzheimer’s arises from an infectious process. So the proper focus of the present debate regarding AD should not be ‘is there an infectious process or processes behind Alzheimer’s?’…….. but rather ‘which one?’ Clearly, whatever the infectious cause behind Alzheimer’s is, it must be a disease that is statistically widespread in the world today and that was also prevalent at the time of Dr. Alzheimer. Presently, in America alone, more than 5 million people, to varying degrees, have lost their memory or cognition to this challenging disease.

Specifically mentioned to this point as possible causes have been: [1] herpes simplex virus type 1 (HSV-I), [2] Chlamydia pneumoniae, and [3] several types of spirochetes. Also mentioned is [4] fungal infection in the AD brain as well.

Mawanda and Wallace’s review (2013) gave seven annotated references as to why Herpes Simplex virus type 1 (HSV-1) “remains questionable” as a cause for Alzheimer’s; nine studies referenced as to why there was “no evidence to suggest an association between Chlamydia pneumoniae infection and AD pathogenesis”; and six “rigorous studies which found no evidence to suggest that spirochetal B. Burgdorferi, is “causally linked to AD” Wallace also mentioned that although Riviere et al. found oral spirochetal Treponema, including T. denticola, T. pectinovorum, T. vincentii, T. amylovorum, T. maltophilum, T. medium, and T. socranskii in a significantly higher proportion of postmortem brain specimens from AD cases than controls. These results have, however, according to Mawanda and Wallace’s review, not been replicated.

As for fungal forms found in the Alzheimer’s brain, this is nothing new. Oskar Fischer, the co-discoverer of Alzheimer’s disease, saw such forms in 1907. But Fischer knew that they were related to Streptothrix, a germ with both bacterial and fungal properties often confused with tuberculosis. The disease actinomycosis was at one time referred to interchangeably with its older bacterial name, the “Streptotriches” (the plural form of Streptothrix). Fischer used such older nomenclature in describing certain forms he saw under his microscope. Furthermore, regarding the thick, black, club-shaped “Drüsen” in Oskar Fischer’s 1907 drawing of senile plaque ― at the time, it was widely acknowledged that such drüsen could result from either infection with Streptothrix, now known as actinomycosis (aktinomycesdruse), a rare disease in humans, or tuberculosis, a disease that by 1882, as Alzheimer prepared to leave for Berlin for his medical education, was understood to be far and away the leading cause of infectious death in Europe. And just ten years before Oskar Fischer found Actinomycosis-like Streptothrix in Alzheimer’s cerebral plaque, Babèş and immunologist Levaditi reported in “On the Actinomycotic Shape of the Tuberculous Bacilli” that typical Actinomyces-like clusters [Drüsen] with clubs appeared in the tissue of rabbits inoculated with tubercle bacilli beneath the dura mater of their brains. Once introduced into the brain this way, reported Babes, TB bacilli not only branched out like the Actinomycosis such as Streptothrix, but they developed rosettes that were identical to the “drüsen” that Oskar Fischer spotted in Alzheimer’s plaque.

What Mawanda and Wallace did maintain however was the emerging evidence that supported an infectious pathogen and two prime suspects for Amyloid beta deposition to the extent that it was going on in Alzheimer’s. This book discusses one of them.

Available on Amazon: Alzheimer’s Disease – How Its Bacterial Cause Was Found And Then Discarded

Introductory YouTube Video: click here

Introductory chapter article is on:



October 8, 2014


Dr. Lawrence Broxmeyer, M.D.


The CDC recently declared:

“Diagnosing Ebola in a person who has been infected for only a few days is difficult, because the early symptoms, such as fever, are nonspecific to Ebola infection and are seen often in patients with more commonly occurring diseases, such as malaria and typhoid fever.”

Only a sin of omission. then, would explain why anyone or any group would not want to specifically mention the most commonly occurring cause of infectious death in Africa ― tuberculosis ― whose sky-high rates in West Africa make Ebola look like a dropper-full of water squeezed into the Mississippi.

If by October, 2014, Ebola had laid claim to what some say is 3,000-plus deaths since its February outbreak, certainly this ought to be weighed in the light of the approximately 600,000 Africans killed by TB in the same time-frame. Furthermore, although TB incidence is decreasing globally, incidence rates are increasing in most of West Africa (1) ― ground zero for the current Ebola outburst. Just as curiously, almost half of all TB cases in the West African Ebola zone are caused by an unusual, yet just as deadly member of tubercular family, Mycobacterium africanum ― a strain of tuberculosis exclusive to West Africa, which is fast becoming a microbe of great public ― and now possibly global concern.

Surely the CDC is aware that there is not a sign or symptom of Ebola, including its hemorrhagic tendencies that cannot be found in acute disseminated miliary (blood-bourne) tuberculosis, once called “galloping consumption” ― the single most feared form of the disease ever. And most likely it is also aware that such tuberculosis has its own viral-like forms, some of which can simulate the Ebola. Such viral TB is generally acknowledged to be TB’s preferred form ― as a survival strategy to storm any inclement conditions the microbe might find itself in. (2)

Then why did the CDC not mention TB, by name, in their short-list of possibilities that could cause Ebola-like symptoms? If such oversight stopped there it would be unremarkable, but it seems to have been carried over in the very design of the most recent diagnostic tests issued to detect Ebola.


In September of 1978, about 40 years ago, a team ― including a 27-year-old medical graduate, training as a clinical microbiologist at the Institute of Tropical Medicine in Antwerp, Belgium, received a blue thermos from Zaire. It was filled with the two 5ml. clotted blood specimens of an African-based Flemish nun. The Belgium doctor who sent it, Jacques Courteille, practicing in Kinshasa, included a note saying that he was at a complete loss for the nun’s mysterious, yet deadly illness. Also, could the samples be tested for Yellow Fever? This thermos had traveled from Zaire’s capital city of Kinshasa, on a Sabena commercial flight to Belgium ― inside its deliverer’s hand luggage. When the samples were received, Peter Piot, the 27-year-old medical graduate and his colleagues, among other things, placed the blood samples under an electron microscope. Piot: “We saw a gigantic worm like structure ― gigantic by viral standards. It’s a very unusual shape for a virus, only one other virus looked like that and that was the Marburg virus.”

But the new “virus” needed a name. Piot relates the interesting tale of how Ebola came to be named as Ebola:

“On that day our team sat together late into the night – we had also had a couple of drinks – discussing the question. We definitely didn’t want to name the new pathogen “Yambuku virus”, because that would have stigmatized the place forever. There was a map hanging on the wall and our American team leader suggested looking for the nearest river and giving the virus its name. It was the Ebola River. So by around three or four in the morning we had found a name. But the map was small and inexact. We only learned later that the nearest river was actually a different one. But Ebola is a nice name, isn’t it?” (3)

Depends upon how you look at it.

Piot’s specimens proved negative for Yellow Fever and he mentions that the tests for Lassa fever and typhoid were also negative. What, then, could it be? Piot: “To isolate any virus material” small amounts of the blood samples were injected into VERO cells and into mice. Several of these mice subsequently and abruptly died ― “a sign that a pathogenic virus was probably present in the blood samples that we had used to inoculate them.”

The fact that the mice died did not mean that it was at the hands of a “pathogenic virus”. Piot’s boss, Stefaan Pattyn, who Piot admitted “could be a bit of a bully”, supposedly specialized in the study of mycobacteria ― tuberculosis and leprosy, yet seemed unaware of the hemorrhagic consequences of acute TB, nor had he taken the time to use special stains and cultures to detect its viral cell-wall-deficient forms. Instead Pattyn followed his current passion. He had recently worked in Zaire for six or seven years and exotic viral illnesses were now “right up his alley”. So Pattyn’s team likewise never really considered a strain of acute miliary TB or its viral cell-wall-deficient forms in his rule-outs for an acute hemorrhagic or epidemic fever ― among them Mycobacterium tuberculosis and Mycobacterium africanum.

The Ebola of its day on steroids, “galloping” acute consumptive tuberculosis could kill in days ― the mere memory of which, just a few generations ago, brought terror to the faces of those who had witnessed and were describing it. Dubos made clear that “galloping consumption” was not an isolated, but a frequent diagnosis in the 19th and early 20th centuries. (4) And despite persistent myths to the contrary, in the early phase of any new TB epidemic from a new and virulent strain, tuberculosis manifests itself as an acute disease and only much later as the chronic pulmonary tuberculosis that we know in today’s western world. An example of this can be found in the high mortality during the 1918 influenza pandemic, when African-Americans were brought to fight in France during World War I ― large numbers of them dying from a fast-tracked tubercular “galloping consumption.”

Many often underestimate the speed, contagiousness and ferocity of a TB epidemic. Khomenko’s 1993 study (5) should have cemented the notion that the explosive contagiousness of just such Ebola and influenza-like viral forms of tuberculosis are exactly the stuff that previous epidemics and pandemics could have been made of. But it didn’t.

In the US, the CDC and NIH seemed to feel differently, ignoring the historic possibility. There was much the same viral passion, at that time over “Influenza”, when in 1990, a new multi-drug-resistant (MDR) tuberculosis outbreak took place in a large Miami municipal hospital. Soon thereafter, similar outbreaks in three New York City hospitals left many sufferers dying within weeks. By 1992, approximately two years later, drug-resistant tuberculosis had spread to deadly mini-epidemics in seventeen US states, and was reported, not by the American, but the international media, as out of control. Viral forms of swine, avian and human TB can be transmitted from one species to another. So can exotic strains of tuberculosis and Mycobacterium africanum, imported into the United States through countries such as Liberia. By 1993 the World Health Organization (WHO) had proclaimed tuberculosis a global health emergency (6). That emergency has never been lifted.
Anderson pointed out that such acute, untreated disseminated, “galloping”, blood-dispersed TB could kill in hours or days (7) ― its mortality, according to Saleem and Azher even today approaching 100%. (8) Ebola itself can take up to a month to kill its victims, said Ben Neuman, an expert in viruses at Britain’s Reading University ― although there are many cases that also kill in hours or days. Not only were tubercular hemorrhaging and fever both mentioned by Fox (9), but hemorrhaging of the serous cavities, the gums, and the nose, into the joints, the skin, and the bowels. Appleman (10), in the American Journal of Ophthalmology, considering massive spontaneous hemorrhages into the vitreous, mentions that Axenfeld considered acute tuberculosis an important possibility in the rule-out for bleeding into the eye. Coughing-up blood has always been a well-known scenario for TB. Hemorrhages of significance fro Read the rest of this entry »

The tuberculin skin test: how safe is safe? -the tuberculins contain unknown forms capable of reverting to cell-wall-deficient mycobacteria

May 27, 2014

Alexander P. Lysenko, Vladimir V.Vlasenko, Lawrence Broxmeyer, Artem P. Lemish, Tatiana P. Novik, Andrei N. Pritychenko

Clinical and Experimental Medical Sciences, Vol. 2, 2014, no. 2, 55 – 73.


® U.S. Library of Congress


Tuberculin is made from proteins derived from tubercle bacilli that have been “killed” by heating. Yet in both Zwadyk’s 1994 study and Bemer-Melchior’s 1999 investigations ‘heat-killed’ tuberculosis and its related mycobacteria, whether in tuberculin, vaccination or otherwise, have dormant, practically indestructible cell-wall-deficient forms which can revert back to virulent TB bacilli “killed” ― by neither heat nor sterilization. The ability and actual preference of mycobacteria such as Mycobacterium tuberculosis and Mycobacterium bovis to form filterable, multi-shaped cell-wall-deficient (CWD) forms and spores in order to survive unfavorable conditions has in fact been known for some time. But the possibility of PPD tuberculins for human use containing such potentially virulent CWD forms, even after autoclaving, sterilizing and ultrafiltration, has not. Autoclaved ultra-filtrates of the various mycobacteria used to produce tuberculin skin tests, consisting of M. Tuberculosis, M. bovis, and M. avium were investigated. All samples were mixed with growth stimulant, incubated, and placed on a special nutrient medium with a 1% agar base. Within 2-10 days after incubation colonies of a variety of non-acid-fast forms were noted, yet all of these proved, through PCR real time with FAM probe to still have antigens in common with their classic tubercular parent form, from which they originated. Moreover, in true cell-wall-deficient fashion, the isolates, upon guinea pig inoculation, did not immediately produce visible lesions, but nevertheless persisted. However, tissue homogenates of the infected animals, once placed on a growth-enhancing medium showed cell-wall-deficient mycobacterial forms interspersed with classical acid-fast rods. And a repeated passage of such tissue homogenates back into non-infected guinea pigs, not only induced small mycobacterial granulomas in their livers, but a distinct increase in acid-fast rods. Moreover, similar cell-wall-deficient mycobacterial forms with acid-fast rods occurred when embryonated chicken eggs were inoculated with PPD tuberculins as well.
The autoclaved and supposedly “sterilized” purified protein derivative [PPD] used in tuberculin skin tests contain cell-wall-deficient forms capable of eventually reverting back to virulent acid-fast tuberculosis, both typical and atypical.

KEYWORDS: Tuberculin; Mycobacterium bovis; thermo stability; Cell-Wall-Deficient mycobacteria


1.WHO Report Global Tuberculosis Control 2010 World Health Organization; WHO Library Cataloguing-in- Publication Data 2010; 218pp p.16
2.Livingston V, Allen RM. Presence of consistently recurring invasive mycobacterial forms in tumor cells.Microscop Soc Bull 1948; 2: 5–18.
3.Livingston, Virginia Wuerthele-Caspe. Cancer: a new breakthrough, Los Angeles: Nash Publishing; 1972. 269pp.
4.Cantwell, A The Cancer Microbe. Los Angeles: Aries Rising Press; 1990. 283pp.
5.Guliang H, Tefu L.Mycobacterium tuberculosis L-forms. Microbial Ecology in Health and Disease 1999; 10: 129-133.
6.Song L-Y, Yan W-S, Zhao T Detection of Mycobacterium tuberculosis in lung cancer tissue by indirect in situ nested PCR; Journal of First Military Medical University; 2002:11.
7.Nalbandian A, Yan BS, Pichugin A, Bronson T, Kramnik I. Lung carcinogenesis induced by chronic tuberculosis infection: the experimental model and genetic control. Oncogen
2009 28(17): 1928-1938.
 8.Anestad G, Hoel T, Scheel O, Vainio K. Atherosclerosis and tuberculosis: are they
both chronic infectious diseases? Scand J Infect Dis 2001;33 (10):797.
9.Livingston VW, Alexander-Jackson E. Mycobacterial forms in myocardial vascular
disease. J. Amer Med Wom Assoc. 1965; 20: 449-452.
10.Broxmeyer L. Is mad cow disease caused by a bacteria? Med Hypotheses. 2004; 63 (4):731-739.
11.Cantwell AR. Variably acid-fast cell wall-deficient bacteria as a possible cause of dermatologic disease.In, Domingue GJ (Ed.) Cell Wall Deficient Bacteria.Reading: Addison-Wesley Publishing Co; 1982. pp. 321-360.
12.Cantwell AR Jr, Kelso DW. Variably acid-fast bacteria in a fatal case of Hodgkin’s
disease. Arch Dermatol 1984; 120 (3):401-402.
13.Centkowski P, Sawczuk-Chabin J, Prochorec M, Warzocha K. Hodgkin’s lymphoma and tuberculosis coexistence in cervical lymph nodes.Leuk Lymphoma; 2005: 46 (3):471-475.
14.Mattman LH Cell Wall Deficient Forms – Stealth Pathogens. CRC Press Boca Ra-
ton 3rd ed., 2001 416pp.
15.Marcova N, Slavchev G, Michailova L, Unique biological properties of Mycobacterium tuberculosis L-form variants: impact for survival under stress. Int Microbiol; 2012: 15 (2): 61-68.
16.Ghosh J, Larsson P, Singh B, Petterson BMF, Islam NM, Sarkar SN, Dasgupta S, Kirsbom LA Sporulation in mycobacteria. Proc Natl Acad Sci USA 2009, 106 (26):10781-10786.
17.Singh B, Ghosh J, Islam NM, Dasgupta S., Kirsebom LA. Growth, cell division and
sporulation in mycobacteria. Antonie van Leewenhoek 2010; 98(2):165-177.
18.Vlasenko VV Tuberculosis in focus of problem contemporarily (in Russian) Vinnica: Nauka, 1998. 350 pp.
19.Lysenko AP, Lemish AP, Krasnikova EL Investigation of the thermal resistance of Mycobacteria tuberculosis. Probl. Tuberk Bolezn. Legk. 2007;(2):42-46.
20.Сsillag A. The mycoccocus form of mycobacteria. J. Gen. Microbiol 1964; 34:.341-
21.Chandrasekhar S, Ratnam S Studies on cell-wall-deficient non-acid fast variants of Mycobacterium tuberculosis. Tuber Lung Dis 1992; 73 (5):273-279.
22.Beran V, Havelkova M, Kaustova L, Dvorska J, Pavlik I Cell-Wall-Deficient forms of
mycobacteria: a review. Veterinarni Medicina 2006; 51, (7): 365-389.
23.Slavchev G, Michailova L, Marcova N Stress-induced L-forms Mycobacterium bovis: a challenge to survivability. New Microbiologica 2013; 36:157-166.
24.Mukamolova G, Turapov OA, Young DI, Kaprelyants AS., Kell DB, Young M A family of autocrine growth factors in Mycobacterium tuberculosis Molecular Microbiology 2002; 46 (3): 623-35.
25.Lysenko AP, Archipov IN, Lemisch АP, Novik TP, Bogdanovich SV Features of antigenic composition of changed forms Mycobacteria tuberculosis. Probl. Tuberk Bolezn. Legk. 2010; 4:41-45.
26.Ma XL et al. Experimental studies on pathogenicity of Mycobacterium tuberculosis
L-form. Chinese Journal of Microekology 1995; 01.
27.Markova N, Slavchev G, Michailova L, Jordanova M Survial of Escherichia coli under lethal heat stress by L-form conversion. Int. J. of Biological Sciences 2010; 6 (4): 303-315.
28. Robinson DH. Pleomorphic mammalian tumor-derived bacteria self-organize as mul- ticellular mammalian eucaryotic like organisms: morphogenetic properties in vitro, possible origin, and possible roles in mammalian «tumor ecologies».Medical Hypothesis
2005; 64 (1):177-185.
29.Seibert FB, Feldmann FM, Davis RL, Richmond IS Morphological, biological, and immunological studies on isolates from tumors and leukemic bloods Ann. N.Y. Acad.
Sci 1970: 174: 690-728.
30.Foddai A., Elliot CT, Grant IR. Rapid assessment of the viability of M.avium subsp. paratuberculosis cells after heart treatment, using an optimized phage amplification
assay. Appl Environ Microbiol 2010; 76:1777-82.
31.Thom M, Morgan JH, Hope JC, Villareal-Ramos B., Martin M., Howard CJ The effect of repeated tuberculin skin testing of cattle on immune responses and disease following experimental infection with Mycobacterium bovis. Vet. Immunol Immunopathol 2004; 102:399-412.
32.Zwadyk P, Down JA, Myers N, et al. Rendering of mycobacteria safe for molecular
diagnostic studies and development of a lysis method for strand displacement ampli-fication and PCR. J Clin Micobiol 1994;32:2140–6.
33.Bemer-Melchior P, Drugeon HB. Inactivation of Mycobacterium tuberculosis for DNA typing analysis. J Clin Microbiol 1999;37:2350–1
34.Pence CD, Ohls, HG. Tuberculosis of the Eye; with Specific Reference to Treatment. Illinois Medical Journal. Chicago April, 1916. 29:4: 307-39
Received: April 29, 2014

Heart Disease – Beyond the Stent And Bypass

April 1, 2014


                    Heart Disease – Beyond the Stent & Bypass

                                                                       by Dr. Lawrence Broxmeyer, MD        grayscale

[Adapted from Heart disease: the greatest ‘risk’ factor of them all. Broxmeyer L. Med Hypoth. 2004;62(5):773-9. PMID:15082105[PubMed – indexed for MEDLINE]

©Copyright 2014

Once upon a time, by the turn of the last century, flying in the face of over a hundred years of research and clinical observation to the contrary, medicine abandoned the link between infection and atherosclerotic heart disease; not because it was ever proven wrong, but because it did not fit in with the trends of a medical establishment convinced that chronic disease such as heart disease must be multifactorial, degenerative and non-infectious.
Yet it was the very inability of ‘established’ risk factors such as hypercholesterolemia, hypertension and smoking to fully explain the incidence and trends in cardiovascular disease that resulted in historically repeated calls to search out an infectious cause, a search that began more than a century ago.
Today, half of US heart attack victims have acceptable cholesterol levels and 25% or more have none of the “risk factors” associated with heart disease, including smoking, high blood pressure or obesity, most of which are not inconsistent with being caused by infection. 7,56 Even the traditionalist’s 2003 assault in JAMA (Journal of the American Medical Association) to ‘debunk’ what they call the “50% risk factor myth” 20 fell woefully short under scrutiny. In one group 30% died of heart disease with a cholesterol of at least 240 mg/dl, a condition which also existed in 21% who did not die during the same period. And the overlap was obvious throughout the so-called risk categories. Under such scrutiny, lead author Greenland conceded that if obesity, inactivity and elevated cholesterol in the elderly are included, just about everyone has a risk factor and he likened the dilemma of people who do or do not wind up with heart disease akin to the susceptibility of people who are exposed and at one time contract tuberculosis, but do not presently have active disease.
In Infections and Atherosclerosis: New Clues from an old Hypothesis? Nieto stressed the need to extend the possible role of infectious agents beyond the three infections which have in recent years been the focus of research: Cytomegalovirus (CMV), Chlamydia pneumonia, and Helicobactor pylori.[39]
Mycobacterial disease shares interesting connections to heart disease. Not only is tuberculosis the only microorganism to depend on cholesterol for its pathogenesis but CDC maps for cardiovascular disease bear a striking match to those of State and regional TB case rates. Why should this be?
Ellis, Hektoen, Osler, McCallum, Swartz, Livingston and Alexander- Jackson all saw clinical and laboratory evidence of a causative relationship between the TB, its related mycobacteria and heart disease. And Xu showed that proteins of mycobacterial origin actually led to experimental atherosclerosis in laboratory animals. Furthermore present day markers suggested as indicators for heart disease susceptibility such as C-Reactive Protein (CRP), interleukin-6 and homocysteine are all similarly elevated in tuberculosis.
Although more than 120 years have passed since its discovery, Mycobacterium tuberculosis is still the leading cause of death globally due to a single infectious agent.[14] This high mortality rate exists in spite of the fact that for over 50 years tuberculosis has been a preventable, diagnosable, and treatable disease.
It therefore behooves us to explore the historical, clinical, and pathological link between heart disease, typical, and atypical tuberculosis.
Attached at the hip, the American Heart Association (AHA), first to push towards medical heart specialization, was actually an offshoot of The National Tuberculosis Association, without whose money and help it would never have survived. In one of its first Bulletins, the AHA (American Heart Association) came up with a long list of the similarities between tuberculosis and heart disease,[2] a view supported by Ellis in The New England Journal of Medicine half a century later.[15] In a ‘name that disease’ Ellis fleshes-out a medical condition who’s mortality rate was 200 to 300 per 100,000, was widespread, and by whom many in their prime were struck down. Treatment was only partially effective. Doctors recommended diet and exercise. Special hospitals were built for it. In a tough decision, Ellis’s readers only recognized the disease as TB when he said it struck 75 years ago, the white plague of the 20th century, for the mortality rate for ischemic heart disease (IHD) at the time of Ellis’s writing was also 200 to 300 persons per 100,000.
Yet it was not until after WWII that the subject was pursued in earnest, and by two women, one of them the first female medical resident in New York. Sometime in 1965, Rutgers’ investigators Virginia Livingston, M.D. and Eleanor Alexander-Jackson PhD, fueled by Fleet and Kerr Grants, working with sterile, post catastrophic heart attack coronary artery specimens, established low-grade tubercular infection, staining ‘acid-fast’ (not decolorized with acid-alcohol) in all ischemic heart disease specimens.[32]
Even in stained slides of the heart muscle itself, Livingston documented small, acid-fast globoidal tubercular bodies which soon appeared to enter into a gradual state of digestion.[ibid]
As far back as 1896, Ludvig Hektoen, Chief Editor of The Journal of Infectious Diseases from 1904-1941, studying how tuberculosis attacked human blood vessels, saw the blood born microbes implanting themselves in vascular walls. Eventually these microbes would penetrate all layers of the arterial wall, including its muscular coat. The offshoot led, often, to the degeneration of whole arterial segments.[23] Since tubercular attack came from the inside of the vascular wall outwards, Hektoen often spotted the initial attack as involving the intimal or advantitial layers.
Even William Osler, arguably the greatest physician since Hippocrates, and to this day an icon for accurate clinical judgment, made clear that arteriosclerosis was frequently associated with tuberculosis.[42]
MacCallum[34] recognized that of all the infectious causes of heart disease, only one, tuberculosis, caused arteriosclerosis. At autopsy, he cited 101 cases of advanced tuberculosis. Of these cases, there were 49 cases in children in the first decade of life ― none of which showed arterial changes. Even in the second, third and fourth decades there were only eleven autopsies who died of TB with moderate cardiovascular sclerosis; while thirteen showed nothing. But by the fifth, sixth, seventh and eighth decades, true to current coronary timetables, there were only two autopsies with normal arteries and [26] with TB arteriosclerosis.[34]
By 1972, pathologist Phillip Schwartz, once a student of Loeffler, became aware that the ‘lardaceous’, waxy degeneration misnamed by Virchow as “amyloid” (starch was called amylum), showed that amyloid (starch-like) degeneration occurred more frequently in elderly cardiovascular systems than hardening and atheromatous lesions of their arteries. But along with this, he noticed that such amyloid degeneration, upon autopsy, usually revealed signs of lingering pulmonary and lymph node tuberculosis.[59]
Classic thought regarding atherosclerosis never was terribly convincing. It supposedly begins with the appearance of cholesterol and fat-laden macrophages (white blood cells) called “foam cells”. The fact that some of these macrophages died, just added to the debris. Macrophages died, tradition dictated, because they could not eliminate cholesterol the way they got rid of bacteria. They simply stuffed themselves compulsively with more and more cholesterol, converting into the large ‘foam cells’ that filled the plaques of advanced atherosclerosis. Macrophages, then, said orthodoxy, literally ate themselves to death at our cardiac blood vessels expense.
But there were obvious flaws to such thinking. First, unlike with other microbes, human macrophages were not that good at eliminating germs like tuberculosis, which in turn kills many of them. Second cholesterol by itself, normally the most abundant steroid in man, was on the rise in Japanese blood during the very decade (1980-1989) when the incidence of coronary heart disease was on its way down.[40] In the meantime, in the US, half the people who had a heart attack had acceptable cholesterol levels, including its HDL and LDL fractions.
Although cholesterol thus seemed an imperfect criterion for determining coronary heart disease, its intimate interaction with TB and the mycobacteria presented extremely interesting coincidental findings. Not only were virulent tuberculosis and the mycobacteria the only pathogens that actually relied upon cholesterol to enter the body’s white blood cells or macrophages,[17] but, it was the Mycobacteria that in addition were able to produce,[31] esterify,[29] take up, modify, accumulate,[4] and promote the deposition of and release[26] of cholesterol.
Orthodox thought then pronounced that smooth muscle cells of the cardiovascular system somehow responded to fat proliferation under the influence of certain platelet factors, which are otherwise supposed to function exclusively in clotting, to eventually cause inflammation. But, to many, it seemed fuzzy logic that inflammation should occur from fat proliferation to begin with. Livingston and Alexander-Jackson’s meticulous work clarified this, finding in all specimens, an infectious agent behind that inflammation and fat propagation.[32] But unfortunately, they worked as “outsiders” at a time when women doctors and scientists weren’t fully accepted.
Others Notice
A 1973 watershed study by Benditt and Benditt reported that cells found in artherogenic plague had a monoclonal origin, that is, they were derived from a single cell population.[6] Confirmatory studies[43,44] prompted the revival and legitimization of a search for an infectious cause. But by concluding that such monoclonal origins were caused by “Chemical mutagens or viruses or both” Benditt and Benditt’s agenda blindsided a third major possibility- tuberculosis and the mycobacteria, each capable of churning out its own monoclonal enzymes, once systemic.[13,45]
It was in no small part as a result of Benditt’s study, much of the world’s scientific and medical community focused on an extremely limited role for tuberculosis and the mycobacteria in heart disease, and at the same time seemed to purposefully marginalize studies that kept seeping into the Index Medicus. For example, in the same year Livingston pursued her heart work at Rutgers, the Russians, unhindered by the American brand of politicized medicine, began proving the link between tuberculosis, atherosclerosis and heart disease.[8,25,27,28]
Which Infection?
Since a 1988 report of raised antibodies against Chlamydia pneumoniae in patients with heart disease appeared, it was hoped that the microbe might be behind atherosclerosis. [21,41,50] Hurting this hypothesis was the low incidence of atherosclerosis in the tropics despite chlamydia’s high frequency there.[52]
Also Loehe and Bittman concluded that although Chlamydia, on occasions, might be present, it was not a causative factor[33] because there was no correlation between the severity or extent of atherosclerosis and the involvement of chlamydial infection at the same site. This report was in concert with Thomas[57] and Gibbs.[19] Combined, these studies seemed to ask: What if Chlamydia pneumoniae was just a passenger bacteria, a friendly bystander? And when, in 1995, MC Sutter’s editorial Lessons For Atherosclerotic Research From Tuberculosis And Peptic Ulcer, warned we might be overlooking the role of a microorganism in atherosclerosis, he did not have chlamydia specifically in mind.[53] Nevertheless, statistics showed that people who used a lot of antibiotics had less heart attacks, and so by 2000 the CDC found that 14% of the cardiologists in Alaska and West Virginia treated heart patients with antibiotics for angina, heart attacks, angioplasty or after by-pass surgery.
And certain antibiotics did seem to work, but the question was their efficacy based upon their anti-Chlamydial activity? Azithromycin, for example has a documented, if moderate activity against certain mycobacteria as well.
Something More conclusive
As the millennium approached, something much more irrefutable was happening. Xu had previously been found that injecting rabbits with normal cholesterol with protein from TB resulted in atherosclerotic changes.[61] Now George and Shoenfeld were implicating these very same proteins in not only the origin of the atherosclerosis in cardiovascular blood vessels but of fatty streak formation there as well.[18] In the meantime, Mukherjee and De Benedictis showed that an increase in antibodies against such tubercular proteins somehow already in the body was actually associated with re-stenosis or future closure of coronary vessels.[37] By 2000, it became obvious to Afek that mice injected with high doses of such tuberculoproteins developed significantly larger areas of atherosclerosis despite the fact that their diet was devoid of high fat content.1 Revisiting this subject, Xu, also using the same tubercular protein (HSP-65), proved the same thing in New Zealand white rabbits.[62] In Xu’s study, such rabbits with normal serum cholesterol injected with the TB preparation led to the formation of all the classic features of arteriosclerosis in humans – the inflammatory cell accumulation and the smooth cell proliferation (ibid) that Livingston and Alexander-Jackson had decades ago attributed to tuberculosis.
In fact, the only finding missing from Xu’s study using normal cholesterolemic animals were “foam cells”: tissue macrophages in which tuberculosis not only lived but thrived in, capable of ingesting material that dissolved during tissue preparation, especially lipids. However, this missing piece of the puzzle was soon remedied when in addition to tuberculous proteins his animals were given a cholesterol rich diet, at which point Xu saw all the lesions found in classic human heart disease, including foam cells. Obviously, tuberculoproteins were overwhelming the systems macrophages, not allowing them to get rid of ingested fat.
Man Thinks – Heaven Laughs
There was also incriminating epidemiologic evidence. The higher incidence of coronary heart disease in young males had a remarkable parallel in bacterial diseases such as TB [52]. And the association between low socioeconomic status and coronary disease found common ground with the incidence of tuberculosis.
The Centers for Disease Control and Prevention (CDC) maps for the total cardiovascular disease and death rates across the country[10] bore a conspicuous similarity to state and regional incidence for CDC TB case rates maps in the United States.9 In addition, the statins, among the most popular drugs in America (Lipitor, Lescol), though inhibitors of Coenzyme-A compound (HMG-CoA or 3-hydroxy-3-methylglutaryl CoA reductase) and as such lowered serum cholesterol levels, did much more.
Specifically, when macrophages were depleted of cholesterol by such pharmacological treatment, mycobacteria such as tuberculosis could not enter the macrophage TB liked to house in, thrive in and depend upon.[17] Furthermore, this block of macrophage uptake with cholesterol depletion was specific only for tuberculosis and the mycobacteria and no other pathogen. In other words, cholesterol played a crucial role in tuberculosis’s establishment of intracellular infection leading both to the long-term survival of the germ and the death of at least1.9 million people a year.
The large British heart protection study took many by surprise when they learned that even lowering “normal” cholesterol levels lowered heart disease risk.[12] This led again to speculation that there must be some other risk factor involved besides cholesterol itself. Lead-author Collins countered that the reason for his study’s finding was that even what we call “normal” cholesterol values are too high, but it is just as easily posited that the lower the blood cholesterol the less likely there is to be chronic mycobacterial infection which would also be of benefit derived from lower than normal cholesterol levels.
It is hardly a coincidence that studies have shown that statins, which indirectly decrease mycobacterial disease, also lower C-reactive protein (CRP). C-reactive protein is an age-old, non-specific protein, first identified in 1930, and then found in the serum of various persons with certain inflammatory and degenerative diseases.[48] Recently an elevated CRP has been touted as an excellent marker for the approximately 25 million US patients that have none of the risk factors associated with heart disease, yet are at risk for a heart attack. However CRP and elevated sedimentation rate have long been excellent markers of active tuberculosis,[22] CRP being present at all times when erythrocyte sedimentation rate (ESR) is elevated but returning to normal faster than ESR as tuberculosis, once treated, becomes inactive. Indeed CRP is a sensitive indicator of the activity of tuberculosis.[5]
Researchers have even tried to neatly tie in excessive weight and its fat cells to indirectly increasing C-reactive protein (CRP) by dumping interleukin-6 (IL-6) into the blood, which, in turn supposedly promotes an inflammatory response, key to signaling the liver, and perhaps the arterial walls themselves, to churn out more CRP. But again, and significantly, higher levels of interleukin-6 are consistently found in either the lung secretions[58] or serum[54] where TB resides. Russell noted sustained release of IL-6 repeatedly issued from human macrophages infected with TB,[49] a defense strategy the microbe uses to possibly create anergic conditions (conditions with lowered immunity) that prevent macrophages from killing them.
Others look towards elevated serum levels of homocysteine, an amino acid also linked as an index of potential heart disease, as the marker of the future even though a homocysteine marker meta-analysis appeared in JAMA, concluding that elevated homocysteine was at most a modest independent predictor of Ischemic Heart Disease (IHD) in healthy populations.[24] Nevertheless homocysteine, it is claimed by some, although not deposited in blood vessel walls like cholesterol, can damage the inside lining of these vessels and make platelets more likely to clot, the scenario which supposedly leads to stroke or heart attacks.
Homocysteine is formed from another amino acid in our diets, methionine. But methionine is also the protein that M. tuberculosis brings systemically into its host to initiate its own protein synthesis.[11] Although Homocysteine can be turned back into methionine and its level lowered in the blood, this requires two essential cofactors: vitamin B12 and “folate” or folic acid, both of which can be lowered in tubercular infection, leading to elevated homocysteine levels.[35,46]
Nieto’s extensive review concludes that the introduction of antibiotic therapies in the 1940s and 1950s could have contributed to the decline of heart disease and heart attacks in the last few decades.[39] Although the tetracyclines appeared in the 1950s it was only after the introduction of the macrolides, in particular erythromycin in the 1960s that the cardiovascular disease mortality curve began to sink. Though it was hypothesized that such decline was the effect of tetracycline and the macrolides against Chlamydia pneumonae, many of the atypical mycobacteria were also sensitive to erythromycin and the tetracycline doxycycline.[36] Also, the antibiotic time-curve Nieto cites excludes the actual introduction of anti-tubercular antibiotics.
Although erythromycin is very effective against C. pneumoniae, the microorganism may persist in the respiratory tract despite adequate blood levels of the antibiotic.[51] There can be no doubt that the availability of antibiotics lowered the morbidity and mortality of cardiovascular disease. Netter mentions that tuberculosis, once often associated with cor pulmonale was less so linked in recent years, probably because of the widespread use of antibiotics and antimicrobial agents.[38]

Conclusion – Runs Silent, Runs Deep
When Nieto stressed the need to extend the possible role of infectious agents beyond the 3 infections which have in recent years been the focus of research: namely, Cytomegalovirus (CMV) C. pneumonia and Helicobactor pylori,[39] was he picking Sir William Osler’s brain regarding that arteriosclerosis was frequently associated with tuberculosis?[42] Still many ridicule the possibility that microbes might be the agents of arteriosclerosis. These were the same minds that in another, far gone era, would have jeered the possibility that syphilis in its late stages had a special preference for the arteries and could cause devastation of major cardiovascular vessels. Eventually though, these minds were proven wrong. But the lessons of syphilis are far-gone ― or are they?
When by 1982, keynote speaker and then Harvard infectious disease guru Louis Weinstein addressed the annual session of the American College of Physicians he mentioned: “We thought initially that the disease (tuberculosis) was disappearing, but we are now seeing up to 27 different syndromes and extrapulmonary forms, etc. It is today’s great mimic, a greater mimic than syphilis ever was.”[60]
In Atherosclerosis and Tuberculosis: Are They Both Chronic Diseases?, after going over the many similarities between tuberculosis and Chlamydia pneumoniae, Anestad focuses on Norwegian 20th century statistics in which two things become obvious. First, that until 1945 tuberculosis was easily the leading cause of infectious death in Norway, surpassing cardiovascular death at the time. Second, that as the diagnosed cases of tuberculosis fell from his statistics, cardiovascular disease increased dramatically until 1975, when its stats too somewhat tapered.[3] At first glance, these statistics seem unrelated even though they are on the same bar graph. But are they? Or are we just looking at another example of Weinstein’s reference to occult TB finding an expanded niche in the cardiovascular system in one of its quests to become “a greater mimic than syphilis ever was”?
In Tuberculosis In Disguise, Rab and Rahman document cases of congestive heart failure and IHD (Ischemic Heart Disease) with chest pain, raised erythocyte sedimentation rate, leukocytosis and inverted T-waves across the chest leads otherwise indistinguishable from the real thing, which turned out to be miliary (systemic) tuberculosis.[47] Rab and Rahman again warned “confusion may occur because tuberculosis can mimic so many other conditions.”
Certainly with tuberculosis and for some time now, we have a human population affected that dwarfs syphilis in its prime. At least a staggering 1.7 million around the globe die of tuberculosis each year, while another 1.9 billion are infected with M. tuberculosis and are at risk for active disease.[14] The World Health Organization (WHO) estimates that 1/3 of the planet has contracted TB.
It would take such a disease to adequately explain the scope of cardiovascular disease, which affects about 61 million people, or almost one-forth of the population in the US alone. Almost 6 million US hospitalizations each year are due to cardiovascular disease. (
The linkage of tuberculosis to acute myocardial infarction and resulting heart attacks is nothing new; [16,30,55] yet serious clinical trials have never been undertaken. And one is left wondering whether the present flurry of trials designed to simply label the markers in the blood that TB and the mycobacteria throw our way is ever really going to quell the near epidemic cardiovascular disease that is presently in our midst.


1. Afek A, George J. Immunization of low-density lipoprotein receptor deficient (LDL-RD) mice with heat shock protein 65 (HSP-65) promotes early atherosclerosis. J Autoimmun 2000;14(2):115¬21.
2. AHA Similarity of tuberculosis and heart disease. Bull Am Heart Assoc 1927;2(5):22.
3. Anestad G, Hoel T. Atherosclerosis and tuberculosis: are they both chronic infectious diseases. Scand J Infect Dis 2001;33:797.
4. Av-Gay Y, Sobouti R. Cholesterol is accumulated by mycobacteria but its degradation is limited to non-pathogenic Heart disease: the greatest ‘risk’ factor of them all 777 fast growing mycobacteria. Can J Microbiol 2000;46(9):826¬31.
5. Bajaj G, Rattan A. Prognostic value of ‘C’ reactive protein in tuberculosis. Indian Pediatr 1989;26(10):1010¬3.
6. Benditt EP, Benditt JM. Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Natl Acad Sci 1973;70(6):1753¬6.
7. Benson RL, Smith KG. Experimental arteritis and arteriosclerosis associated with streptococcal inoculations. Arch Pathol 1931;12:924¬40.
8. Bruade VI. Cardiovascular diseases in conjunction with pulmonary tuberculosis (pathological-anatomical findings). Sov Med 1966;29(12): 104-7.
9. CDC Map: TB case rates, United States, 2001. Atlanta Georgia: US Department of Health, Education and Welfare CDC; 2001.
10. CDC Map total cardiovascular disease – 1995 death rate. Atlanta Georgia: US Department of Health, Education Welfare CDC; 1995.
11. Chun T. Induction of M3-restricted T lymphocyte responses by N- formulated peptides derived from Mycobacterium tuberculosis. J Exp Med 2001;193(10):1213¬20.
12. Collins R, Armitage J. MRC/BHF heart protection study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomized placebo-controlled trial. Lancet 2003;361(9374):2005¬16.
13. David HL. Bacteriology of the mycobacterioses. Atlanta Georgia: Center for disease control, Mycobacteriolgy branch; 1976.
14. Dye C, Scheele S. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. JAMA 1999;282:677¬86.
15. Ellis JG. Plague tuberculosis and plague atherosclerosis. The New England J Med 1977;296(12):695.
16. Ferrari-Sacco A, Ferraro U. Myocardial Infarct and Pulmonary Tuberculosis. Discussion of 2 cases of myocardiocoronary disease appearing during hospitalization in a sanatorium. Minerva Cardioangiol 1966;14(8):465¬75.
17. Gatfield J, Pieters J. Essential role for cholesterol in entry of mycobacteria in macrophages. Science 2000;288:1647¬750.
18. George J, Shoenfeld Y. Enhanced fatty streak formation in C57BL/ 6J Mice by immunization with heat shock protein-65 arteriosclerosis. Thromb Vasc Biol 1999;19:505¬10.
19. Gibbs RG, Sian M. Chlamydia pneumoniae does not influence atherosclerotic plaque behavior in patients with established carotid artery stenosis. Stroke 2000;31:2930¬5.
20. Greenland P, Knoll MD. Major Risk Factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA 2003;290(7):891¬7.
21. Gurfinkel E, Bozovich G. Chlamydia pneumoniae: inflammation and instability of the atherosclerotic plaque. Atherosclerosis 1998;140(Suppl 1):31¬5.
22. Haghighi L, Doust JY. C-Reactive protein in pulmonary tuberculosis. Dis Chest 1966;50(6):624¬6.
23. Hektoen L. The vascular changes of tuberculous meningitis. J Exper Med 1896:112.
24. Wilson PW. Homocysteine and coronary heart disease: how great is the hazard? JAMA 2002;288(16):2042¬3.
25. Kamyshnikova VS, Kolb VG. Biochemical factors involved in atherogenesis in pulmonary tuberculosis. Probl Tuberk 1984;11:48¬52.
26. Kamyshnikov VS, Kolb VG. Lipid metabolism and atherogenesis in tuberculosis in experimental animals. Probl Tuberk 1993;4:53¬5.
27. Kazykhanov NS. Lung tuberculosis in patients with atherosclerosis. Sov Med 1965;28(8):37¬44.
28. Kazykhanov NS. Arteriosclerosis in patients with pulmonary tuberculosis. Kardiologiia 1967;7(10):137.
29. Kondo E, Kanai K. Accumulation of cholesterol esters in macrophages incubated with mycobacteria in vitro. Jpn J Med Sci Biol 1976;29(3):123¬37.
30. Kossowsky WA, Rafii S. Letter: acute myocardial infarction in miliary tuberculosis. Ann Intern Med 1975;82(6):813¬4.
31. Lamb DC, Kelly DE. A sterol biosynthetic pathway in mycobacterium. FEBS Lett 1998;437(1-2):142¬4.
32. Livingston V. Cancer: a new breakthough. Los Angeles: Nash Publishing; 1972.
33. Loehe F, Bittmann I. Chlamydia pneumoniae in atherosclerotic lesions of patients undergoing vascular surgery. Ann Vasc Surg 2002;16(4):467¬73.
34. MacCallum WG. Acute and chronic infections as etiological factors in arteriosclerosis. In: Cowdry EV, editor. Arteriosclerosis A survey of the problem. New York: MacMillan Co; 1933. p. 355¬62.
35. Markkansen T, Levanto A. Folic acid and vitamin B12 in tuberculosis. Scand J Haemat 1967;4:283¬91.
36. Molavi A, Weinstein L. In viro activity of erythromycin against atypical mycobacteria. J Infect Dis 1971;123:216¬9.
37. Mukherjee M. De Benedictis association of antibodies to heat- shock protein-65 with percutaneous transluminal coronary angioplasty and subsequent restenosis. Thromb Haemost 1996;75(2):258¬60.
38. Netter FH HEART The Ciba Collection of Medical Illustrations. West Caldwell New Jersey CIBA-GEIGY Corporation 1992.
39. Nieto FJ. Infections and atherosclerosis: new clues from an old hypothesis. Am J Epidemiol 1998;148(10):937¬48.
40. Okayama A. Ueshima changes in total serum cholesterol and other risk factors for cardiovascular disease in Japan, 1980¬1989. Int J Epidemiol 1993;22:1038¬47.
41. Orfila JJ. Seroepidemiological evidence for an association between Chlamydia pneumoniae and atherosclerosis. Atherosclerosis 1998;140(Suppl 1):11¬5.
42. Osler W. Diseases of the arteries. In: Osler W, MacCrae T, editors. Modern medicine Its theory and practice in original contributions by Americans and foreign authors, vol. 4. Philadelphia, PA: Lea & Fabiger; 1908. p. 426¬47.
43. Pearson TA, Wang BA. Clonal characteristics of fibrous plaques and fatty streaks from human aortas. Am J Pathol 1975;81:379¬87.
44. Pearson TA, Dillma JM. Clonal characteristics of cutaneous scars and implications for atherogenesis. Am J Pathol 1981;102:49¬54.
45. Purwantini E, Gillis TP. Presence of F420-dependent glucose-6- phosphate dehydogenase in Mycobacterium and Nocardia species, but absence from Streptomyces and Corynebacterium species and methanogenic Archaea. FEMS Microbiol Lett 1997;146(1):129¬34.
46. Qureshi GA, Baig SM. The neurochemical markers in cerebrospinal fluid to differentiate between aseptic and tuberculous meningitis. Neurochem Int 1998;32(2):197¬203.
47. Rab SM, Rahman M. Tuberculosis in disguise. Brit J Dis Chest 1967;61:90¬4.
48. Rifai N, Ridker PM. Inflammatory markers and coronary heart disease. Curr Opin Lipidol 2002;13(4):383¬9.
49. Russel DG. Sturgill-Koszycki S why intracellular parasitism need not be a degrading experience for Mycobacterium. Phil Trans R Soc Lond B 1997;352:1303¬10.
50. Saikku P, Leinonen M. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1988;2:983¬6.
51. Smith CB, Friedewald WT. Shedding of Mycoplasma pneumonia after tetracycline and erythromycin therapy. New Eng J Med 1967;276:1172¬5.
52. Stille W, Dittmann R. Arteriosclerosis as a sequela of chronic Chlamydia pneumoniae infection. Herz 1998;23(3):185¬92.
53. Sutter MC. Lessons for atherosclerosis research from tuberculosis and peptic ulcer. Can Med Assoc J 1995;152(5):667¬70.
54. Tang S, Xiao H. Changes of proinflammatory cytokines and their receptors in serum from patients with pulmonary tuberculosis. Zhonghua Jie He He Hu Xi Za Zhi 2002;25(6):325¬9.
55. Tarakanova KN, Terent’eva GM. Myocardial infarct in patients with pulmonary tuberculosis. Probl Tuberk 1972;50(4):90¬1.
56. Thom DH, Grayston JT. Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary artery disease. JAMA 1992;268:68¬72.
57. Thomas M, Wong Y. Relation between direct detechion of Chlamydia pneumoniae DNA in human coronary arteries at postmortem examination and histological severity (Stary garding) of associated atherosclerotic plaque. Circulation 1999;99:2733¬6.
58. Tsao TC, Hong J. Increased TNF-alpha, IL-1 beta and IL-6levels in the bronchoalveolar lavage fluid with the upregulation of their mRNA in macrophages lavaged from patients with active pulmonary tuberculosis. Tub Lung Dis 1999;79(5):279¬85.
59. Schwartz P. Amyloid degeneration and tuberculosis in the aged. Gerontologia 1972;18(5-6):321¬62.
60. Weinstein L. Bacterial endocarditis, TB changing presentation. Internal Med News 1982;15(11):2.
61. Xu Q. Dietrich Induction of arteriosclerosis in normocholesterolemic mice and rabbits by immunization with heat shock protein 65. Arterioscler Thromb 1992;12:789¬99.
62. Xu Q, Kleindienst R. Increased expression of heat shock protein 65 coincides with a population of infiltrating T lymphocytes in atherosclerotic lesions of rabbits specifically responding to heat shock protein 65. J Clin Invest 1993;91:2693¬702.

©Copyright 2014
All Rights Reserved