Archive for the 'Lawrence Broxmeyer MD' Category

CWD Tuberculosis Found in Spongiform Disease Formerly Attributed to Prions: Its Implication towards Mad Cow Disease, Scrapie and Alzheimer’s

May 9, 2017

LINK OUT TO RESEARCH ARTICLE

Journal of MPE Molecular Pathological Epidemiology 2017 Vol. 3 No. 3: 3

Lysenko AP PhD,
Broxmeyer L MD,
Vlasenko VV PhD,
Krasochko PA PhD,
Lemish AP and
Krasnikova EL

Abstract

The TSE’S or transmissible spongiform encephalopathies, include bovine spongiform encephalopathy (also called BSE or “mad cow disease”), Creutzfeldt– Jakob disease (CJD) in humans, and “scrapie” in sheep or goats (caprine spongiform encephalopathy).  They remain a mystery, their cause still hotly debated. Current mad cow diagnosis lies solely in the detection of late appearing “prions”, an acronym for hypothesized, geneless, misfolded proteins, somehow claimed to cause the disease. Yet laboratory preparations of prions contain other things, which could include unidentified bacteria or viruses. And the only real evidence that prion originator Stanley Prusiner had in his original paper that the disease agent behind “Scrapie” in sheep and goats was devoid of DNA or RNA– was based upon the fact that he couldn’t find any. Furthermore, the rigors of prion purification alone, might, in and of themselves, have killed any causative microorganism and Heino Dringer, who did pioneer work on their nature, candidly predicts “it will turn out that the prion concept is wrong.” Roels and Walravens as well as Hartly traced Mad Cow to Mycobacterium bovis. Moreover, epidemiologic maps of the origins and peak incidence of Mad Cow in the UK, suggestively match those of England’s areas of highest bovine tuberculosis, the Southwest. The neurotaxic potential of bovine tuberculosis has for some time been well known. By 1911 Alois Alzheimer called attention to “a characteristic condition of the cortical tissue which Fischer referred to as ‘spongy cortical wasting” in Alzheimer’s disease (AD). But behind AD, Fischer suspected a microbe called Streptothrix which was constantly being mistaken and confused for tuberculosis. Our present investigation of the TSEs clearly shows cell-wall-deficient (CWD) tubercular mycobacteria present, verified by molecular analysis, ELISA, PCR and microscopy to cause spongiform encephalopathy.

Keywords: Prions; Scrapie; The Spongiform Encephalopathies; Alzheimer’s disease; The etiology of Alzheimer’s Disease; Mycobacterium tuberculosis Complex

Received: April 05, 2017; Accepted: April 27, 2017; Published: April 29, 2017

 

References

1   Curto M, Reali C, Palmieri G, Scintu F, Schivo ML, et al. (2004) Inhibition of Cytokines Expression in Human Microglia Infected with Virulent  and  Nonvirulent  Mycobacteria.  Neurochem  Internat  44: 381-392.

2    Broxmeyer  L,  Sosnowska  D,  Miltner  E,  Chacón  O,  Wagner  D,  et al. (2002) Killing of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens. J Infect Dis 186: 1155-1160.

3    Randall PJ, Hsu NJ, Lang D, Cooper S, Sebesho B, et al. (2014) Neurons are host cells for Mycobacterium tuberculosis. Infect Immun 82: 1880-1890.

4    Manuelidis  EE,  Manuelidis  L  (1989)  Suggested  Links  Between Different Types of Dementias: Creutzfeldt-Jakob disease, Alzheimer disease, and Retroviral CNS Infections. Alzheimer Dis Assoc Disord 3: 100-109.

5    Stockman S (1911) The habits of British ticks found on sheep and cattle. J Comp Pathol 24: 229-37.

6    Fischer O (1911) The spongious loss of the bones, a special process of destruction of the cerebral cortex. Z ges Neurol Psychiat 7: 1-33.

7   Babes V, Levaditi C (1897) On the Actinomycotic Shape of the Tuberculosis Bacilli (Sur la Forme Actinomycosique du Bacilli de la Tuberculosis). Arch of Med Exp et D’anat 9: 1041-1048.

8    Dunkin GW (1936) Paratuberculosis of Cattle and Sheep. Section of Comparative Medicine. Proc R Soc Med 30: 83-90

9    Chauveau A: Transmission of virulent diseases by the ingestion of virulent principles in the digestive tract. Gaz de Paris: p 45.

10  Klebs E (1870) On the history of tuberculosis. Virchows Arch F path Anat :p 291

11  Gerlach  AC  (1870)  On  the  inoculability  of  tuberculosis  and  the perilla, and on the transferability of the latter by feeding. Virchows Arch F path Anat 11: 297.

12  Pfeiffer DU (1994) The role of a wildlife reservoir in the epidemiology of bovine tuberculosis. Massey University, Dept of Veterinary Clinical Sciences, New Zealand.

13 Bourne J, Donnelly C (2001) An epidemiological investigation into bovine tuberculosis third report of the Independent Scientific Group on Cattle TB.

14  Francis  J  (1947)  Bovine  Tuberculosis:  Including  a  Contrast  with Human Tuberculosis. Staples Press Limited, London: p 220.

15  Taubes G (1986) The game of the name is fame. But is it science? Discover 7: 28-52.

16 Hadlow WJ, Prusiner SB, Kennedy RC, Race RE (1980) Brain tissue from persons dying of Creutzfeldt-Jacob disease causes scrapie-like encephalopathy in goats. Ann Neurol 8: 628-631.

17  Griffith JS (1967) Self-replication and scrapie. Nature 215: 1043-4.

18  Prusiner SB (1995) The  prion  diseases. Sci Am 272: 48-51.

19  Pethe K, Bifani P, Drobecq H, Sergheraert C, Debrie AS, et al. (2002) Mycobacterial heparin-binding hemagglutinin and laminin-binding protein share antigenic methyllysines that confer resistance to proteolysis. Proc Natl Acad Sci USA 2002 99: 10759-10764.

20  Tsubuki S, Takako Y (2003) Dutch,    Flemish,    Italian    and Arctic mutations of App and resistance of Abeta to physiologically relevant proteolytic degradation. Lancet 361: 1957-1958.

21  Lasmézas  CI,  Deslys  JP  (1997)  Transmission  of  the  BSE  agent to mice in the absence of detectable abnormal prion protein. Science 275: 402-405.

22  Baker  CA, Martin D, Manuelidis L (2002) Microglia from  Creutzfeld– Jakob disease-infected brains are   infectious and   show specific mRNA activation profiles. J Virol 76: 10905-10915.

23  Botsios S, Manuelidis L (2016) CJD and Scrapie Require Agent- Associated  Nucleic  Acids  for  Infection.  J  Cell  Biochem  117: 1947-1958.

24  Abalos P, Retamal P (2004) Tuberculosis: a re-emerging zoonosis? Rev Sci Tech 23: 583-94.

25  O’Reilly LM, Daborn CJ (1995) The epidemiology of Mycobacterium bovis infections in animals and man: a review. Tuber Lung Dis 76: 1-46.

26  Grange JM (2001) Mycobacterium bovis infection in human beings. Tuberculosis 81: 71-77

27  Mattman LH (2001) Cell Wall Deficient Forms: Stealth Pathogens.CRC Press 3 (416).

28  Xalabarder C (1958) Electron microscopy of tubercle bacilli. Excerpta Medica. Sec XV Chest Dis 11: 467-473.

29  Xalabarder C (1963) The Nature of So-Called Atypical Mycobacteria. Neumol Cir Torax 24: 259-74.

30  Csillag A (1964) The mycococcus form of mycobacteria. Journ of Gen Microbio 34: 341-352

31  Shleeva  MO,  Salina  EG,  Kaprel’iants  AS  (2010)  Dormant  form  of Mycobacterium tuberculosis. Mikrobiologiia 79: 3-15

32  Zhang Y, Yang Y, Woods A, Cotter RJ, Sun Z (2001) Resuscitation of dormant Mycobacterium tuberculosis by phospholipids or specific peptides. Biochem Biophys Res Commun 284: 542-547.

33 Marcova N, Slavchev G, Michailova L (2012) Unique biological properties of Mycobacterium tuberculosis L-form variants: impact for survival under stress. Int. Microbiol 15: 61-68.

34  Shleeva MO, Mukamolova GV, Telkov MV, Berezinskaia TL, Syroeshkin AV et al. (2003) Formation of nonculturable Mycobacterium tuberculosis and their regeneration. Mikrobiologiia 72: 76-83.

35  Prusiner SB (2014) Madness and Memory: The Discovery of Prions – A New Biologic Principle of Disease. Yale University Press.

36  Hass G, Huntington R (1943) Amyloid. III The properties of amyloid deposits occurring in several species under diverse conditions. Arch Pathol 35: 226.

37 Schwartz P (1972) Amyloid degeneration and tuberculosis in the aged. Gerontologia 18: 321-362.

38 Delgado WA (1997) Amyloid deposits in labial salivary glands identified by electron microscopy. J Oral Pathol Med 26: 51-52.

39  de Beer FC, Nel AE (1984) Serum amyloid A protein and C-reactive protein levels in pulmonary tuberculosis: relationship to amyloidosis. Thorax 39: 196–200.

40  Tomiyama T, Satoshi A (1994) Rifampicin prevents the aggregation and neurotoxicity of amyloid B protein in vitro. Biochem Biophys Res Commun 204: 76-83.

41  Chauhan A, Madiraju MV, Fol M, Lofton H, Maloney E, et al. (2006) Mycobacterium  tuberculosis  Cells  Growing  in  Macrophages  Are Filamentous and Deficient in FtsZ Rings. J. Bacteriol 188: 1856-1865.

42 Markova N, Michailova L, Kussovski V, Jourdanova M (2008) Formation of Persisting Cell Wall Deficient Forms of Mycobacterium bovis BCG during Interaction with Peritoneal Macrophages in Guinea Pigs. Electronic Journal of Biology 4: 1-10

43 Thacore H, Willett HP (1966) The formation of spheroplasts of Mycobacterium tuberculosis in tissue culture cells. Am Rev Respir Dis 93: 786-796.

44 Lysenko AP, Vlasenko AP, Broxmeyer L (2014) Phenomenon of variability of mycobacteria and its use for detection of a tuberculosis infection.

45 Lysenko AP, Vlasenko VV, Broxmeyer L, Lemish AP, Novik TP, et al. (2014) The tuberculin skin test: how safe is safe?  The tuberculins contain unknown forms capable of reverting to cell-wall-deficient mycobacteria. Clinical and Experimental Medical Sciences 2: 55-73.

46  Lysenko  AP,  Broxmeyer  L,  Vlasenko  V,  Krasochko  PA,  Lemish  AP, et al. (2016) Further evidence for Cancer as Cell-wall-deficient Mycobacterial Disease. J Mol Pathol Epidemiol 1: 1-12.

47  Lysenko AP, Vlasenko VV, Lemish AP (2014) Detection of mycobacteria in tis- sues by means of the differentiating  immunoperoxidase staining. Tuberculos i bolezni legkhih. 10: 55-58.

48  Harry EJ (2001) Bacterial cell division: regulating Z-ring formation. Mol Microbiol 40: 795-803.

49  Errington J, Daniel RA, Scheffers DJ (2003) Cytokinesis in bacteria. Microbio Mol Biol Rev 67: 52-65.

50  Xalabarder C (1970) L-forms of chronic mycobacteria and nephritis. Publ Inst Antituberc(Barcelona) Supple 7:7-83.

51 Seidel B, Thomzig A, Buschmann A, Groschup MH, Peters R, et al. (2007) Scrapie agent (strain 263K) can transmit disease via the oral route after persistence in soil over years. PLoS One 2: e435.

52  Ghodbane R, Mba Medie F, Lepidi H, Nappez C, Drancourt M (2014) Long-term survival of tuberculosis complex mycobacteria in soil. Microbiology 160: 496-501.

53  Insanov AB, Gadzhiev FS (1996) Comparative Analysis of the Results of Spinal Fluid Microbiological Study in Children and Adults Who Suffered from Tuberculous Meningitis. Probl tuberk. 5: 25–28.

54  Slavchev  G,  Michailova  L,  Markova  N  (2013)  Stress-induced L-forms of M. bovis: challenge to survivability. New Microbiologica 36: 157-166.

55  Calmette A, Valtis J, Lacomme A (1928) New experimental research on tuberculous ultravirus. CR Acad Sci 186: 1778-1781.

56  Xiao X, Miravalle L, Yuan J, McGeehan J, Dong Z, et al. (2009) Failure to Detect the Presence of Prions in the Uterine and Gestational Tissues from a Gravida with Creutzfeldt – Jakob disease. Am J Pathol 174: 1602-1608.

57  Brieger EM (1949) The Host Parasite Relationship in Tuberculous Infection. Tubercle 30: 242-253.

58 Brieger EM, Glauert AM (1952) A Phase-Contrast Study of Reproduction in Mycelial Strains of Avian Tubercle Bacilli. J Gen Microbiol 7: 287-294.

59  Prusiner SB (2004) Development of the Prion Concept. Prion Biology and Diseases, Cold Spring Harbor Laboratory Press: pp 89-141.

60  Pattison IH (1988) Fifty years with scrapie: a personal reminiscence. Vet Rec 123: 661-666.

61  Pattison IH, Jones KM (1967) The possible nature of the transmissible agent of scrapie. Vet Rec 80: 7.

62  Gerston KF, Blumberg L, Tshabalala VA, Murray J (2004) Viability of mycobacteria in formalin-fixed lungs. Hum pathol 35: 571-575.

63  Vinnie DS, Mary R (2002) Does formaldehyde kill Myco tuberculosis? Tech Bull Histopath 2: 37-38.

64  Alzheimer A, Forstl H, Levy R (1991) On Certain Peculiar Diseases of Old Age. History of Psychiatry 2: 71-101.

65  Goedert M (2015) Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled Aß, tau and α-synuclein. Science 349: 1255555.

66 Schwab C, Hosokawa M, McGeer PL (2004) Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease. Exp Neurol 188: 52-64

67 Mawanda F, Wallace R (2013) Can infections cause Alzheimer’s disease? Epidemiol Rev 35: 161-80.

68  Alteri CJ, Xicahténcati-Cortes J, Hess S, Caballero-Olin G, Girón JA,et al. (2007) Mycobacterium Tuberculosis Produces Pili during Human Infection. Proc Natl Acad Sci USA 104: 5145-5150.

69 Jordal PB, Dueholm MS, Larsen P, Petersen SV, Enghild JJ, et al. (2009)  Widespread  abundance  of  functional  bacterial  amyloid in mycolata and other gram-positive bacteria. Appl Environ Microbiol 75: 4101-4110.

 

Killing of Mycobacterium avium and Mycobacterium tuberculosis by a Mycobacteriophage Delivered by a Nonvirulent Mycobacterium: A Model for Phage Therapy of Intracellular Bacterial Pathogens

January 12, 2017
Lawrence Broxmeyer, Danuta Sosnowska, Elizabeth Miltner, Ofelia Chacon, Dirk Wagner, Jeffery McGarvey, Raul G. Barletta, and Luiz E. Bermudez

Killing of Mycobacterium avium and Mycobacterium tuberculosis by a Mycobacteriophage

The Journal of Infectious Diseases

ABSTRACT

Mycobacterium avium causes disseminated infection in patients with acquired immune deficieny syndrome. Mycobacterium tuberculosis is a pathogen associated with the deaths of millions of people worldwide annually. Effective therapeutic regimens exist that are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms. The present study describes a system using Mycobacterium smegmatis, an avirulent mycobacterium, to deliver the lytic phage TM4 where both M. avium and M. tuberculosis reside within macrophages. These results showed that treatment of M. avium–infected, as well as M. tuberculosis –infected, RAW 264.7 macrophages, with M. smegmatis transiently infected with TM4, resulted in a significant time and titer  dependent reduction in the number of viable intracellular bacilli. In addition, the M. smegmatis vacuole harboring TM4 fuses with the M. avium vacuole in macrophages. These results suggest a potentially novel concept to kill intracellular pathogenic bacteria and warrant future development.

REFERENCES
1. Bloom B. Tuberculosis: pathogenesis, protection and control. Washington,DC: American Society for Microbiology Press, 1995.
2. Surveillance TWIGP. Anti-tuberculosis drug resistance in the world. Geneva:World Health Organization Global Tuberculosis Programme, 1997.
3. Inderlied CB, Kemper CA, Bermudez LE. The Mycobacterium avium complex. Clin Microbiol Rev 1993; 6:266–310.
4. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338: 853–60.
5. Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus–associated opportunistic infections in the United
States in the era of highly active antiretroviral therapy. Clin Infect Dis 2000 ; 30(Suppl 1):S5–14.
6. Falkinham JO 3rd. Epidemiology of infection by nontuberculous mycobacteria. Clin Microbiol Rev 1996; 9:177–215.
7. Guthertz LS, Damsker B, Bottone EJ, Ford EG, Midura TF, Janda JM. Mycobacterium avium and Mycobacterium intracellulare infections in patients with and without AIDS. J Infect Dis 1989; 160:1037–41.
8. Heifets L. Susceptibility testing of Mycobacterium avium complex isolates. Antimicrob Agents Chemother 1996; 40:1759–67.
9. Horsburgh CR Jr. Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. N Engl J Med 1991; 324:1332–8.
10. Chaisson RE, Benson CA, Dube MP, et al. Clarithromycin therapy for bacteremic Mycobacterium avium complex disease: a randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team. Ann Intern Med 1994; 121:905–11.
11. Young LS, Wiviott L, Wu M, Kolonoski P, Bolan R, Inderlied CB. Azithromycin for treatment of Mycobacterium avium–intracellulare complex infection in patients with AIDS. Lancet 1991; 338:1107–9.
12. Bermudez LE, Kolonoski P, Young LS. Roxithromycin alone and in combination with either ethambutol or levofloxacin for disseminated Mycobacterium avium infections in beige mice. Antimicrob Agents Chemother 1996; 40:1033–5.
13. Dube MP, Sattler FR, Torriani FJ, et al. A randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy. California Collaborative Treatment Group. J Infect Dis 1997; 176:1225–32.
14. Holzman D. Phage as antibacterial tool. Genetic Engineering News 1998; 18:11–16.
15. Ford ME, Stenstrom C, Hendrix RW, Hatfull GF. Mycobacteriophage TM4: genome structure and gene expression. Tuber Lung Dis 1998; 79:63–73.
16. Foley-Thomas EM, Whipple DL, Bermudez LE, Barletta RG. Phage infection,transfection and transformation of Mycobacterium avium complex and Mycobacterium paratuberculosis. Microbiology 1995; 141:1173–81.
17. Bermudez LE, Parker A, Goodman JR. Growth within macrophages increases the efficiency of Mycobacterium avium in invading other macrophages by a complement receptor–independent pathway. Infect Immun 1997; 65:1916–25.
18. Jacobs WR Jr, Kalpana GV, Cirillo JD, et al. Genetic systems for mycobacteria. Methods Enzymol 1991; 204:537–55.
19. Black CM, Bermudez LE, Young LS, Remington JS. Coinfection of macrophages modulates interferon gamma and tumor necrosis factor–induced activation against intracellular pathogens. J Exp Med 1990; 172:977–80.
20. Hafner R, Inderlied CB, Peterson DM, et al. Correlation of quantitative bone marrow and blood cultures in AIDS patients with disseminated Mycobacterium avium complex infection. J Infect Dis 1999; 180:438–47.
21. Sula L, Sulova J, Stolcpartova M. Therapy of experimental tuberculosis in guinea pigs with mycobacterial phages DS-6A, GR-21 T, My-327. Czech Med 1981; 4:209–14.
22. Rastogi N, Labrousse V. Extracellular and intracellular activities of clarithromycin used alone and in association with ethambutol and rifampin against Mycobacterium avium complex. Antimicrob Agents Chemother 1991; 35:462–70.
23. Bermudez LE, Young LS. New drugs for the therapy of mycobacterial infections. Curr Opinion Infect Dis 1995; 8:428–38.
24. Sturgill-Koszycki S, Schlesinger PH, Chakraborty P, et al. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science 1994; 263:678–81.
25. Clemens DL, Horwitz MA. Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J Exp Med 1995
; 181:257–70.
26. de Chastellier C, Lang T, Thilo L. Phagocytic processing of the macrophage endoparasite, Mycobacterium avium, in comparison to phagosomes which contain Bacillus subtilis or latex beads. Eur J Cell Biol 1995; 68:167–82.
27. Gomes MS, Paul S, Moreira AL, Appelberg R, Rabinovitch M, Kaplan G. Survival of Mycobacterium avium and Mycobacterium tuberculosis in acidified vacuoles of murine macrophages. Infect Immun 1999; 67:3199–206.

QUESTIONING THE ZIKA VIRUS

January 8, 2017

DR. LAWRENCE BROXMEYER, MD

QUESTIONING THE ZIKA.pdf

Broxmeyer L. Questioning the Zika
Virus. J Mol Path Epidemol. 2017, 1:1.

© Under License of Creative Commons Attribution 3.0 License

ABSTRACT

A growing body of health officials in Brazil are doubting that the Zika “virus” is responsible for the rise in birth defects in parts of that country. Zika, along with yellow fever, has been tossed into the family Flaviviruses; the Latin “flavus” meaning yellow. But unlike yellow fever, the vast majority of Zika’s symptoms for the last 70 years have been mild to non-existent. Despite disseminations by the lay and scientific press, there are serious questions whether Zika causes microcephaly at all. If by March, 2016 the Brazilian Ministry of Health reported 2,197 suspected cases of microcephaly, only 11.48% of these were Zika-positive. Zika is widespread throughout Brazil and South and Central America, yet the bulk of microcephaly cases are confined to the costal tip of Northeastern Brazil. Furthermore, despite extensive testing, no known mosquito-borne arbovirus or any other virus has to this point been proven to cause Brazilian microcephaly.

While Zika was being portrayed as “the most alarming health crisis to hit Brazil in decades”, tuberculosis and its related mycobacteria were quietly gaining a stranglehold and building an ecologic niche in the very Northeastern region being hit by epidemic microcephaly. Why was this important? With NE Brazilian microcephaly/Zika we are probably dealing with a mosquito-fueled environmental zoonosis – a disease that can be transmitted from animals to humans – such as primates, and to a lesser extent birds (Mycobacterium avium), and rodents (Mycobacterium microti), all mentioned in the Zika literature. Add to this the penchant of Brazilians to illegally capture and keep mycobacterial-laden wild monkies and exotic birds as pets or for revenue,and  you have a potential zoonotic time-bomb ready to explode once the proper vectors presents themselves. Three mosquito vectors have been steadily populating Northeastern Brazil: namely Culex quinquefasciatus, the Aedes aegypti and the Aedes albopictus – all of which have the capacity to transmit viral-like forms of the mycobacteria associated with HIV and through direct laboratory investigation with microcephaly. Perhaps it is time to rethink what’s really behind Brazilian Microcephaly and other symptomatology from the “Zika” agent.

KEYWORDS: The Zika virus; microcephaly; Aedes aegypti; Flaws in Zika diagnostics; Mycobacterium tuberculosis; Rhesus monkey; Brazil; CWD mycobacteria; Yellow fever; Flaviviruses; Systemic lupus erythmatosus; SLE; Neurtralization tests.

Received: October 07, 2016; Accepted: November 16, 2016; Published January 02, 2017

REFERENCES

  1. Dick, G.W.A., Kitchen, S.F. and Haddow, A.J. (1952) Communications: Zika Virus—Isolations and Serological Specificity. Transactions of the Royal Society of Tropical Medicine and Hygiene, 46, 509-520. http://dx.doi.org/10.1016/0035-9203(52)90042-4
  2. Bresalier, M, Mazumdar, P (ed.), Kroker, K (ed.) & Keelan, J (ed.) 2008, Neutralizing Flu: ‘Immunological devices’ and the making of a virus disease. in Crafting Immunity: Working Histories of Clinical Immunology. Ashgate, London, pp. 107-144.
  3. F.J. Fenner and R.V. Blanden, ‘History of Viral Immunology’, in A.L. Notkins (ed.), Viral Immunology and Immunopathology, New York, London: Academic Press, 1975, pp. 1–25 at pp.13–14.
  4. Van Helvoort T., “History of virus research in the 20th century: the problem of conceptual continuity”, History of Science 1994; 32(2):185-235
  5. Castets M, Boisvert H, Grumbach F, Brunel M, Rist N. Tuberculosis bacilli of the African type: preliminary note. Rev Tuberc Pneumol (Paris). 1968 Mar; 32(2):179-84.
  6. Broxmeyer, L, Kanjhan, R. (2016) Does Zika Really Have the Capacity to Affect the Nervous System and Cause Microcephaly or Intracranial Calcifications? Modern Research in Inflammation, 5, 20-30.  http://www.scirp.org/journal/PaperInformation.aspx?paperID=66412
  7. Musso D, Nilles EJ, Cao-Lormeau VM. Rapid spread of emerging Zika virus in the Pacific area. Clin Microbiol Infect 2014;20:O595-6.
  8. MacNamara FN. Zika virus: a report on three cases of human infection during an epidemic of jaundice in Nigeria. Trans R Soc Trop Med Hyg 1954; 48: 139-45.
  9. Fagbami AH. Zika virus infections in Nigeria: virological and seroepidemiological investigations in Oyo State. J Hyg (Lond) 1979; 83: 213-9.
  10.  Moore DL, Causey OR, Carey DE, et al. Arthropod-borne viral infections of man in Nigeria, 1964-1970. Ann Trop Med Parasitol 1975; 69: 49-64.
  11. Olson JG, Ksiazek TG, Suhandiman, Triwibowo. Zika virus, a cause of fever in Central Java, Indonesia. Trans R Soc Trop Med Hyg 1981; 75: 389-93.
  12. Simpson DI. Zika virus infection in man. Trans R Soc Trop Med Hyg 1964; 58: 335-8.
  13. Zika virus: clinical evaluation and disease. Atlanta: Centers for Disease Control and Prevention http://www.cdc.gov/zika/hc-providers/clinicalevaluation.html.
  14. Duffy MR, Chen T-H, Hancock WT, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 2009; 360: 2536-43.
  15. Petersen LR, Jamieson DJ, Powers AM, and Honein MA. Zika Virus. N Engl J Med 2016; 374:1552-1563 April 21, 2016.
  16. Yamada S, Pobutsky A. Micronesian Migrant Health Issues in Hawaii: Part 1    Californian Journal of Health Promotion 2009, Volume 7, Issue 2, 16-31.
  17. Opening of Third STOP Tuberculosis in the Pacific. Monday, 31 July 2006. Press Release: Secretariat of the Pacific Community (SPC) Scoop Independent News.  http://www.scoop.co.nz/stories/WO0607/S00560.htm
  18. O’Hara CJ, Groopman JE. The ultrastructural and immunohistochemical demonstration of viral particles in lymph nodes from human immunodeficiency virus-related and nonhuman immunodeficiency virus-related lymphadenopathy syndromes. Hum Pathol. 1988; 19(5): 545–549.
  19. Nambuya A, Sewankambo N. Tuberculosis lymphadenitis associated with human immunodeficiency virus (HIV) in Uganda. J Clin Pathol. 1988; 41: 93–96.
  20. Voetberg A, Lucas SB. Tuberculosis or persistent generalized lymphadenopathy in HIV disease. Lancet. 1991; 337: 56–57.
  21. Bader JP. Reproduction of RNA humor viruses. Comprehensive Virol. 1975; 4: 253.
  22. Driggers RW, Ho CY, Korhonen EM, Kuivanen S, Jääskeläinen AJ et al. Brief Repot: Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities. N Engl J Med. 2016 Jun 2; 374(22):2142-51.
  23. Biedler JL et al. (1973) Morphology and growth, tumorgenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Research 33: 2643-2652
  24. Helson L et al. (1975) Human neuroblastoma in nude mice. Cancer Research 35: 2594-2599] https://www.mskcc.org/research-advantage/support/technology/tangible-material/human-neuroblastoma-cell-line-sk-n-sh
  25. Miller JM, Miller LD, Olson C, Gillette KG. Virus-like particles in phytohemagglutinin-stimulated lymphocyte cultures with reference to bovine lymphosarcoma. J Natl Cancer Inst. 1969;43:1297–1305
  26. Alexander-Jackson, E. Microscopic and Submicroscopic Phases of P. Cryptocides from Fresh Lymphocytic leukemia. J Int Acad Metab 1978. 1:2:9-18
  27. Klieneberger-Nobel E. Origin, development and signifincance of L-forms in bacterial cultures. J Gen Microbiol 1949; 3: 434–442.
  28. Seibert FB, Feldman RL. Morphological, biological, and immunological studies on isolates from tumors and leukemic bloods. Ann NY Acad Sci. 1970; 174(2): 690–728.
  29. Mattman L. Cell Wall Deficient Forms—Stealth Pathogens. Boca Raton: CRC Press; 1993.
  30. Randall PJ, Hsu N-J, Lang D, et al. Neurons Are Host Cells for Mycobacterium tuberculosis. Appleton JA, ed. Infection and Immunity. 2014; 82(5):1880-1890
  31. FDA. Fact Sheet for Health Care Providers: Interpreting Zika Virus RNA Qualitative Real-Time RT-PCR Test Results. April 28th, 2016. http://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM498275.pdf
  32. Butler D. Zika and birth defects: what we know and what we don’t – Experts fear a major epidemic of Zika-linked birth defects, but can’t yet be sure. Nature. 21 March 2016. http://www.nature.com/news/zika-and-birth-defects-what-we-know-and-what-we-don-t-1.19596
  33. Good RC. Simian Tuberculosis: Immunological Aspects. Annals of the New York Acad of Sciences. September 1968. 154: 200-213.
  34. Johnson PDR, Azuolas J, Lavender CJ, Wishart E, Stinear TP, Hayman JA, et al. Mycobacterium ulcerans in mosquitoes captured during outbreak of Buruli ulcer, southeastern Australia. Emerg Infect Dis. 2007 Nov. Available from  http://wwwnc.cdc.gov/eid/article/13/11/06-1369.
  35. Lavender CJ, Fyfe JAM, Azuolas J, Brown K, Evans RN, Ray LR, et al. (2011) Risk of Buruli Ulcer and Detection of Mycobacterium ulcerans in Mosquitoes in Southeastern Australia. PLoS Negl Trop Dis 5(9): e1305. doi:10.1371/journal.pntd.0001305.
  36. Banerjee, R., Banerjee, B.D., Chaudhury, S. and Hati, A.K. (1991) Transmission of Viable Mycobacterium leprae by Aedes aegypti from Lepromatous Leprosy Patients to the Skin of Mice through Intermittent Feeding. Tropical and Geographical Medicine, 42, 97-99.
  37. Narayanan, E., Manja, K.S., Kirchheimer, W.F. and Balasubrahmanyan, M. (1972) Occurrence of Mycobacterium leprae in Arthropods. Leprosy Review, 43, 194-198. http://dx.doi.org/10.5935/0305-7518.19720026
  38. Narayanan, E., Sreevatsa, Kirchheimer, W.F. and Bedi, B.M. (1977) Transfer of Leprosy Bacilli from Patients to Mouse Footpads by Aedes egypti. Leprosy Review, 49, 181-186.
  39. Narayanan, E., Sreevatsa, Raj, A.D., Kirchheimer, W.F. and Bedi, B.M. (1978) Persistence and Distribution of Mycobacterium leprae in Aedes egypti and Culex fatigans Experimentally Fed on Leprosy Patients. Leprosy in India, 50, 26-37.
  40. Golyshevskaya, V.I. (1991) The Role of Coccoid Ultrafine Forms of Mycobacteria in the Transmission of the Mycobacterial Infection. Pneumoftiziologia, 40, 11-13.
  41. Silva-Krott IM, Brock K, Junge RE. “Determination of the Presence of Mycobacterium avium on Guam as Precursor to Reintroduction of Indigenous Bird Species, Pacific Conservation Biology 4 (1998): 227–31.
  42. Smith M. WHO Raises Yellow Fever Warnings Urban outbreak in Angola might go global. MedPage. http://www.medpagetoday.com/infectiousdisease/generalinfectiousdisease/57846
  43. Manson P. Tropical Diseases. A Manual of the Diseases of Warm Climates. 1st edition. London: Cassell & Co.; 1898. p. 127.
  44. Lindenbach, BD et al. (2007). “Flaviviridae: The Viruses and Their Replication”. In Knipe, D. M.; P. M. Howley. Fields Virology (5th Ed.). Philadelphia, PA: Lippincott Williams & Wilkins. p. 1101
  45. Rivers TM. Filterable Viruses a Critical Review. From the Hospital of the Rockefeller Institute, New York Received for publication January 31, 1927 Journal of Bacteriology, Vol. XIV, No. 4; 217-257:220.
  46. Finlay C. The Mosquito Hypothetically Considered as the Transmitting Agent of Yellow Fever. Yale J Biol Med. 1937 Jul; 9(6): 589–604.
  47. Eckstein, Gustav. Noguchi. New York: Harper & Brothers, 1931 419pp
  48. Reed W. et al. The etiology of yellow fever. An additional note. J Amer Med Assoc. 1901; 36:431–440.
  49. Yellow fever. A compilation of various publications. Results of the work of Maj. Walter Reed, Medical Corps, United States Army, and the Yellow Fever Commission. 61st Congress, 3rd session. Senate Doc No 822. Washington: Government Printing Office; 1911.
  50. Del Regato, JA. James Carroll: a biography. Ann Diagn Pathol. 1998 Oct; 2(5):335-49.
  51. Kendall, AI. Observations Upon the Filterability of Bacteria, Including a Filterable Organism Obtained From Cases of Influenza. Science. August 7, 1931 74:1910.
  52. Krotz D. First Detailed Microscopy Evidence of Bacteria at the Lower Size Limit of Life. Berkeley Lab. February 27, 2015. http://newscenter.lbl.gov/2015/02/27/ultra-small-bacteria/
  53. Sternberg ML. George Miller Sternberg, A Biography. American Medical Association. Chicago. 1920. 331pp: p.118.
  54. Elliott CA. A clinical study of yellow fever: observations made in Guayaquil, Ecuador in 1918. Arch Intern Med (Chic). 1920;25(2):174-205
  55. Noguchi, H.: Etiology of Yellow Fever. J. Exper. M. 29:547, 1919; 30:1, 87, 401, 1919.
  56. Noguchi H. Etiology of yellow fever: II. Transmission experiments on yellow fever. J Exp Med. 1919; 29:565–584.
  57.  Noguchi H. Etiology of yellow fever: V. Properties of blood serum of yellow fever patients in relation to Leptospira icteroides. J Exp Med. 1919; 30:9–12.
  58. Stokes A, Bauer JH, Hudson N. The transmission of yellow fever to macacus rhesus: preliminary note. JAMA. 1928; 90(4):253-254.
  59. Mattman LH. Cell Wall Deficient Forms. CRC Press. Cleveland. 1974. 411 pp.
  60. Inada R, Ido Y, Hoki R, Kaneko R, and Ito H. The etiology, mode of infection, and specific therapy of Weil’s disease (Spirochaetosis Icterohaemorrhagica). J. Exp. Med., 23, 377-402. 1916.
  61. Hudson NP. Communication – Adrian stokes and yellow fever research: A tribute. Transactions of the Royal Society of Tropical Medicine and Hygiene.  60:2:170-174. 1966
  62. Letter from Noguchi to Simon Flexner, 1928 Noguchi’s papers. Record Group 450  N689 of the Rockefeller University Archives. http://dimes.rockarch.org/xtf//view?docId=ead/FA121/FA121.xml;query=;brand=default;chunk.id=contentsLink;doc.view=contents#aspace_ref36_m4i
  63. Extracts from letter of Hideyo Noguchi, Accra, March 9th, 1928 to Dr. Simon Flexner. http://dimes.rockarch.org/xtf//view?docId=ead/FA121/FA121.xml;query=;brand=default;chunk.id=contentsLink;doc.view=contents#aspace_ref36_m4i
  64. Received in NYC, NY Western Union Cablegram from Hideyo Noguchi to Dr. Simon Flexner March 16th, 1918 4/HN45C LCO  RUS  50.
  65. Noguchi to Russell of Rockefeller Institute  (Letter)  Accra  March 25, 1928.   http://dimes.rockarch.org/xtf//view?docId=ead/FA121/FA121.xml;query=;brand=default;chunk.id=contentsLink;doc.view=contents#aspace_ref36_m4i
  66. Ekstein G. Hideyo Noguchi. Medical Bulletin College of Medicine University of Cincinnati, April, 1929. 5:3:15-17
  67. Jacob NJ, Henein SS. Nontuberculous Mycobacterial infection of the CNS in Patients with AIDS. Southern Medical Journal. Vol. 86 No. 6, 1993
  68. Bishburg E et al. Central Nervous System Tuberculosis with the Acquired Immunodeficiency Syndrome and Its Related Complex. Annals of Internal Medicine, 105: pp. 210-13.
  69. Lambertucci JR, Rayes AM, Nunes F, Landazuri-palacios EJ and Nobre V.  Fever of Undetermined Origin in Patients with the Acquired Immunodeficiency Syndrome in Brazil: Report on 55 Cases. Rev. Inst. Med. trop. S. Paulo Vol.41 N.1 São Paulo Jan./Feb. 1999
  70. Thomson, A. (1894) Microcephaly and Infantile Hemiplegia in the Journal of Anatomy and Physiology, Normal and Pathological, Human and Comparative. Humphray, G.M., Turner, W. and McKendrick, J.G., Eds., Vol. 28, Charles Griffin and Company, London, 419-444.
  71. Gluecksohn-Waelsch, S. (1957) The Effect of Maternal Immunization against Organ Tissues on Embryonic Differentiation in the Mouse. Journal of Embryology and Experimental Morphology, 5, 83-89.
  72. Warthin, A. S., and Cowie, D. M. A Contribution in the Casuistry of Placental and Congenital Tuberculosis. Journ. Inf. Dis., 1 (1904): 140.
  73. Rao, V. V., Gupta, E. V., and Thomas, I. M. Chromosome Damage in Untreated Tuberculosis Patients. Tubercle. 71, no. 3 (September 1990): 169–72.
  74. Lakimenko, L. N. Changes in the Mitotic Regime of a Cell Culture under the Influence of Sensitins. Biull Eksp Biol Med., 81, no. 2 (February 1976): 237–39.
  75. Golubchik, I. S., Lakimenko, L. N., and Lazovskaia, A. L. Effect of Tuberculin on the Mitotic Regime in Cell Cultures Biull Eksp Biol Med., 73, no. 5 (May 1972): 105–7.
  76. Nogales-Ortiz, F., and Tarancon, I. The Pathology of Female Genital Tuberculosis. Obstet. Gynecol., 53 (1979): 422-428.
  77. Favoretto S, Araujo D, Oliveira D, Duarte N, Mesquita F et al. First detection of Zika virus in neotropical primates in Brazil: a possible new reservoir. bioRxiv Apr 20, 2016  pp 1-3. http://dx.doi.org/10.1101/049395
  78. Macdonald, David (Editor) (1985). Primates. All the World’s Animals. Torstar Books. pp. 1-50.
  79. Duarte-Quiroga, A; Estrada, A (2003). “Primates as pets in Mexico City: an assessment of the species involved, source of origin, and general aspects of treatment”. Am J Primatol 61: 53–60.
  80. Valderrama X, Robinson JG, Attygalle AB, Eisner T. (2000). “Seasonal Anointment with Millipedes in a Wild Primate: A Chemical Defense against Insects?” Journal of Chemical Ecology 26 (12): 2781–2790
  81. Michel AL, Huchzermeyer HF (1998) The zoonotic importance of Mycobacterium tuberculosis: Transmission from human to monkey. Journal of the South African Veterinary Association 69:64–65
  82.  Alfonso R, Romero RE, Diaz A, Calderon MN, Urdaneta G, Arce J, et al. (2004) Isolation and identification of mycobacteria in New World primates maintained in captivity. Veterinary Microbiology 98:285–295
  83. Capuano SV, Croix DA, Pawar S, Zinovik A, Myers A, Lin PL, et al. Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection. Infection and Immunity. 2003; 71:5831–5844
  84. Une, Y. and Mori, T., “Tuberculosis as a zoonosis from a veterinary perspective”, Comp. Immunol. Microb. 2007 Sep; 30(5-6):415-425, http://tinyurl.com/mxoag5d
  85. Okia NO, George PV, Tukei PM, Kafuko GW, Lule M, Sekyalo E, et al. Arbovirus survey in wild birds in Uganda. East Afr Med J. 1971; 48(12):725–31. PMID: 5148604
  86. Spinage CA. African Ecology – Benchmarks and Historical Perspectives. Springer Science & Business Media. Jan 28, 2012 1562pp:  p.1124
  87. Garmany, Jeff (2011). Situating Fortaleza: Urban space and uneven development in northeastern Brazil Cities (Elsevier) 28 (1): 45–52
  88. Ranking das maiores regiões metropolitanas do Brasil. 10/12/2010   http://g1.globo.com/brasil/noticia/2010/12/confira-o-ranking-das-maiores-regioes-metropolitanas.html
  89. NatureServe. InfoNatura: birds, mammals, and amphibians of Latin América (Web application). 32nd edition. Arlington, Virginia. NatureServe. 2010.
  90. Marini MA, Garcia FI: Bird conservation in Brazil. Conservation Biology 2005, 19(3):665–671
  91. Alves RRN, Lima JRF, Araújo HF: The live bird trade in Brazil and its conservation implications: an overview. Bird Conservation International 2012. http://dx.doi.org/10.1017/S095927091200010X.
  92. Alves RRN, Nogueira E, Araujo H, Brooks S: Bird-keeping in the Caatinga, NE Brazil. Hum Ecol 2010, 38(1):147–156.
  93. Gama TF, Sassi R: Aspectos do comércio Ilegal de Pássaros Silvestres na Cidade de João Pessoa, Paraíba, Brasil. Gaia Scientia 2008, 2(2):1–20.
  94. Silva JMC, Souza MA, Bieber AGD, Carlos CJ. Aves da Caatinga: Status, uso do habitat e sensitividade. In: Ecologia e Conservação da Caatinga. 1st Edition. Edited by Leal IR, Tabarelli M, Silva JMC. Recife, Brasil. Universitária da UFPE; 2003:237–274
  95. Fernandes-Ferreira H, Mendonça SV, Albano C, Ferreira FS, Alves RRN: Hunting, use and conservation of birds in Northeast Brazil. Biodivers Conserv. 2012, 21: 221-244.
  96. Dhama, K., Mahendran, M., Tiwari, R., Dayal Singh, S., Kumar, D., Singh, S., & Sawant, P. M. (2011). Tuberculosis in Birds: Insights into the Mycobacterium avium Infections. Veterinary Medicine International, 2011, 712369. http://doi.org/10.4061/2011/712369
  97. Marx, F. (2011) Tuberculosis in the Region of the Americas – Regional Report 2011: Epidemiology, Control and Financing. Pan-American Health Organization, Regional Office of the World Health Organization. Washington DC, 53pp
  98. Starke JR, Jacobs RF, Jereb J. Review: Resurgence of tuberculosis in children. J  Pediatr. 1992 Jun; 120(6):839-55
  99. Melo, A.S.O., Malinger, G., Ximenes, R., Szejnfeld, P.O., Sampaio, S.A. and Bispo de Filippis, A.M. (2016) Zika Virus Intrauterine Infection Causes Fetal Brain Abnormality and Microcephaly: Tip of the Iceberg? Ultrasound in Obstetrics & Gynecology, 47, 6-7.
  100. Anga G, Barnabas R, Kaminiel O, Tefuarani Vince NJ, Ripa P, Riddell M and Duke T. The aetiology, clinical presentations and outcome of febrile encephalopathy in children in Papua New Guinea. Annals of Tropical Paediatrics 2010, Jun 21. 30(2): 109-18.
  101. Zika Virus in Papua New Guinea. Centers for Disease Control and Prevention (CDC); National Center for Emerging and Zoonotic Infectious Diseases (NCEZID); Division of Global Migration and Quarantine (DGMQ). Last updated: April 29, 2016 http://wwwnc.cdc.gov/travel/notices/alert/zika-virus-papua-new-guinea
  102. There is no outbreak of Zika virus in PNG. Press release: PORT MORESBY (POST COURIER) March 21, 2016] http://www.postguam.com/news/pacific/there-is-no-outbreak-of-zika-virus-in-png/article_53a1e6fc-ee7e-11e5-bec4-0f3e0b066b8e.html
  103. Eccles, G. Papua New Guinea’s Tuberculosis Pandemic. March 28, 2016 The Diplomat http://thediplomat.com/2016/03/papua-new-guineas-tuberculosis-pandemic/
  104. Koch R., “Die Ätiologie der Tuberkulose” (“The Aetiology of Tuberculosis”), Mitteilungen aus dem Kaiserlichen Gesundheitsamte 1884; 2:1-88.
  105. Zika travel information. Atlanta: Centers for Disease Control and Prevention, January 2016 http://wwwnc.cdc.gov/travel/page/zika-travel-information
  106. Gourinat AC, O’Connor O, Calvez E, Goarant C, Dupont-Rouzeyrol M. Detection of Zika virus in urine. Emerg Infect Dis 2015; 21:84-86.
  107. Korhonen EM, Huhtamo E, Smura T, Kallio-Kokko H, Raassina M, Vapalahti O. Zika virus infection in a traveller returning from the Maldives, June 2015. Euro Surveill 2016; 21.
  108. Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau VM. Potential sexual transmission of Zika virus. Emerg Infect Dis 2015; 21:359-361.
  109. Foy BD, Kobylinski KC, Chilson Foy JL, et al. Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis 2011; 17:880-882.
  110. McCarthy M. Zika virus was transmitted by sexual contact in Texas, health officials report. BMJ 2016; 352: i720-i720.
  111. Venturi G, Zammarchi L, Fortuna C, et al. An autochthonous case of Zika due to possible sexual transmission, Florence, Italy, 2014. Euro Surveill 2016;21.
  112. Transmission of Zika virus through sexual contact with travelers to areas of ongoing transmission — continental United States, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:215-216.
  113. Zika virus infection: global update on epidemiology and potentially associated clinical manifestations. Wkly Epidemiol Rec 2016;91:73-81.
  114. Lauritsen J. Has Provincetown Become Protease Town? [Internet]. Available from: http://www.virusmyth.com/aids/hiv/jlprotease.html
  115. Hellyer TJ, Desjardin LE, Teixeira L, Perkins MD, Cave MD, Eisenach KD. Detection of Viable Mycobacterium tuberculosis by Reverse Transcriptase-Strand Displacement Amplification of mRNA. Clin. Microbiol. March 1999. 37:3:518-523.
  116. Cáceres M. Birth of the Zika Industry. The Vaccine Reaction. May 16, 2016.
  117. Centers for Disease Control and Prevention. CDC Concludes Zika Causes Microcephaly and Other Birth Defects.gov Apr. 13, 2016.
  118. Centers for Disease Control and Prevention (CDC). Zika Virus. Clinical evaluation and disease. April 19, 2016 http://www.cdc.gov/zika/hc-providers/clinicalevaluation.html
  119. Kasper DL, Braunwald E, Hauser S, Longo D, Jameson JL et al. Harrison’s Principles of Internal Medicine 16th Edition (July 23, 2004), McGraw-Hill Professional. 2607 p.
  120. Klase ZA, Khakhina S, Schneider ADB, Callahan MV, Glasspool-Malone J, Malone R (2016) Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome. PLoS Negl Trop Dis 10(8).
  121. Schlossberg D. Clinical Infectious Disease. Cambridge University Press. Apr 23, 2015. 1508pp p.481
  122. Cantwell AR Jr, Kelso DW, Jones JE. Histologic observations of coccoid forms suggestive of cell wall deficient bacteria in cutaneous and systemic lupus erythematosus. Int J Dermatol. 1982 Nov; 21(9):526-37.
  123. Doria A, Canova M, Tonon M, Zen M, Rampudda E, Bassi N,et al. Infections as triggers and complications of systemic lupus erythematosus. Autoimmun Rev 2008; 8:24-8.
  124. Ghosh K, Patwardhan M, Pradhan V. Mycobacterium tuberculosis infection precipitates SLE in patients from endemic areas. Rheumatol Int 2009; 29:1047-50.
  125. Purice S, Mitu S, Popescu T, Guran M, Vintilă M, Suţă G. The relationship between systemic lupus erythematosus and tuberculosis. Med Interne 1982; 20:191-6
  126. Prabu VNN, Agrawal S. Systemic lupus erythematosus and tuberculosis: A review of complex interactions of complicated diseases. Journal of Postgraduate Medicine 56, Num. 3, 2010, pp. 244-250.
  127. Zika Virus RNA Qualitative Real-Time RT-PCR. Focus Diagnostics, Inc. For use under an Emergency Use Authorization only Instructions for Use. http://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM498278.pdf
  128. R. Nowell, “Comparative Mosquito Collection Data from the Southern Mariana Islands (Diptera: Culicidae),” Proceedings of the California Mosquito and Vector Control Association 48 (1980): 112–6.
  129. Flexner, S. Simon Flexner Papers, 1891-1946. Noguchi to Flexner Aug. 11, 1924. Rockefeller Archive Center. http://www.rockarch.org/collections/individuals/ru/
  130. Mlakar, J., Korva, M., Tul, N., et al. (2016) Brief Report: Zika Virus Associated with Microcephaly. New England Journal of Medicine, 374, 951-958. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1600651.
  131. Rubin, E.J., Greene, M.F. and Baden, L.R. (2016) Editorial: Zika Virus and Microcephaly. New England Journal of Medicine, 374, 984-985. http://www.nejm.org/doi/full/10.1056/NEJMe1601862]
  132. The Pan American Health Organization/World Health Organization (PAHO/WHO). Epidemiological Update. Zika virus infection. 16 October 2015. http://www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=&gid=32021&lang=en

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Further Evidence for Cancer as a Cell-Wall-Deficient Mycobacterial Disease

December 5, 2016

A.P. Lysenko PhD, L. Broxmeyer MD, V.V. Vlasenko PhD, P.A. Krasochko PhD, A.P.Lemish PhD, and E.A. Krasnikova

Further Evidence for Cancer as a Cell-Wall-Deficient Mycobacterial Disease.pdf

Corresponding author:
Lawrence Broxmeyer, M.D

© Under License of Creative Commons Attribution 3.0 License

first-page_cancer_lysenko

Received: October 07, 2016; Accepted: November 03, 2016; Published: November
14, 2016

 

ABSTRACT

In 2014, Buehring reported that Bovine Leukemic Virus (BLV), a common oncogenic retrovirus of cattle, was present in some humans, primarily localized to the breast epithelium  ―  the  very  cell  type  from  which  most  breast  malignancies  arise.  By 2015, there appeared data (Buehring, 2015) supporting that as many as 37% of human breast cancer cases could be attributable to BLV exposure. But if recent estimates suggest over 83% of U.S. dairy operations are currently positive for BLV, they also show that approximately 68% are positive for cell-wall-deficient Mycobacterium avium subspecies paratuberculosis (MAP). Although tubercular lung infection has been said to cause 11 times the incidence of lung cancer as normal control subjects, it is its cell-wall-deficient (CWD) forms (also called L-forms) that have recently repeatedly been found through genetic analysis and appropriate stains in such cancer tissue ― suggesting that CWD tuberculosis or atypical tuberculosis “is likely to be involved in the occurrence or development of lung carcinoma”. A similar relationship between tubercular L-forms and the genesis of the very breast cancer addressed in the aforementioned BLV viral trials. This is not a coincidence. L-forms (CWD forms) predominate and are crucial to the survival of mycobacteria in vivo and they have been documented by fluorescence microscopy in all intracellular macrophage-grown M. tuberculosis observed. From its origin, the very concept of the “BLV leukemic virus” has been on shaky, unstable ground. In 1969, veterinarians Janice and Lyle Miller from the University of Wisconsin-Madison spotted C-shaped “virus-like” particles in cattle lymphosarcoma insisting that these were similar to other C-type viruses “regarded as the cause of leukemia in other species.” But by 1978, scientists at Downstate reported atypical mycobacterial forms, including its preferred filterable virus-sized “L” or cell-wall-deficient (CWD) forms in not only leukemia but all other malignancies ― all having, as their common denominator the continuous presence of mycobacterial C-shaped forms.

Tracing back to techniques similar to Miller and Millers original BLV study we found in the very lyophilized antigens present in commercial kits for the diagnosis of BLV (AgBLV), these very same CWD (cell-wall-deficient) mycobacteria and mycobacterial DNA in all BLV samples ― which when introduced into guinea pigs stimulated the same antibody as occurred when mycobacteria-infected internal organ homogenates themselves were injected into other guinea pigs. It is therefore assumed that the Bovine Leukemic Virus (BLV) is being mistaken for viral-like forms of cell-wall-deficient (CWD) atypical tubercular mycobacteria. Since latent tubercular infection, as well as the administration of BCG and tuberculin also results in persistent CWD forms, their possible role in carcinogenesis is also considered.

KEYWORDS: Cancer; Mycobacterium tuberculosis; Bovine Leukemic Virus; BLV; Mycobacteriophages

 

REFERENCES:

1   Rous PA (1911) Sarcoma of the fowl transmissible by an agent separable from the tumour cells. J Exp Med 13: 397-411.

2    Bittner JJ (1936) Some possible effects of nursing on the mammary gland tumour incidence of mice. Science 84: 162.

3    Van Helvoort T (1994) History of virus research in the 20th century: the problem of conceptual continuity. History of Science 32: 185-235.

4    Livingston V (1972) Cancer: A New Breakthrough. Nash Publishing p: 269.

5  Livingston V (1970) Specific type of organism cultured from malignancy: bacteriology and proposed classification.  Ann NY Acad Sci 174: 636-654.

6    Duran-Reynals F (1950) Neoplastic infection and cancer. Am J Med 8: 440-511.

7    Glover T, Scott MA (1926) Study of the Rous chicken sarcoma no 1. Canada Lancet Pract 66: 49-62.

8    Diller I (1970) Experiments with mammalian tumor isolates. Ann NY Acad Sci 174: 655-674.

9    Miller JM, Miller LD, Olson C, Gillette KG (1969) Virus-like particles in phytohemagglutinin-stimulated lymphocyte cultures with reference to bovine lymphosarcoma. J Natl Cancer Inst 43: 1297-1305

10 Miller JM (1974) Animal model of human disease. Malignant lymphoma. Am J Pathol 75: 417-420.

11  Sorensen DK, Dutta SK, Hammer RF, Larson VL, Perman V, et al. (1970) Bovine lymphocytic leukemia: studies of etiology, pathogenesis and mode of transmission. Progress Report no. 10 to the U.S. Atomic Energy Commission, 1969-1970 p: 38

12  Alexander-Jackson EA (1954) specific type of microorganism isolated from animal and human cancer: bacteriology of the organism. Growth 18: 37-51.

13  Klieneberger-Nobel E (1949) Origin, development and significance of L-forms in bacterial cultures. J Gen Microbiol 3: 434-442.

14  Mattman LH (2000) Cell wall deficient forms: stealth pathogens. CRC Press.

15  Kashala O, Marlink R, Ilunga M, Diese M, Gormus B, et al. ( 1994) Infection with human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic viruses among leprosy patients and contacts: correlation between HIV-1 cross-reactivity and antibodies to lipoarabinomannan. J Infect Dis 169: 296-304.

16  Glover T (1930) The bacteriology of cancer. Canada Lancet Pract 75: 92-111.

17  Mazet G (1941) Etude Bacteriologique sur la Maladie d’ Hodgkin. Montpellier Med pp: 1-6.

18  Livingston V, Allen R (1948) Presence of consistently recurring invasive myco- bacterial forms in tumor cells. Microscop Soc Bull 2: 5-18.

19  Wuerthele-Caspe V (1949) Mycobacterial forms observed in tumors. J Am Med. Womens Assoc 4: 135-141.

20  Alexander-Jackson  E  (1976)  Progenitor  Cryptocides,  The  Specific Pleomorphic Microorganism Isolated From Cancer. J Int Acad Metab 5: 31-39.

21  Alexander-Jackson E (1978) Microscopic and Submicroscopic Phases of P. Cryptocides from Fresh Lymphocytic leukemia. J Int Acad Metab 1: 9-18.

22  Diller I, Diller W (1965) Intracellular acid-fast organisms isolated from malignant tissues. Trans Am Micr Soc 84: 138-148.

23  Diller I, Donnelly A, Fisher M (1967) Isolation of pleomorphic, acid- fast organisms from several strains of mice. Cancer Res 27: 1402-1408.

24 Seibert F, Feldmann F, Davis R, Richmond I (1970) Morphological, biological, and immunological studies on isolates from tumors and leukemic bloods. Ann N Y Acad Sci 174: 690-728.

25  Wang A, Xie J (1998) Infection of mycobacterium tuberculosis in lung cancer. Zhongguo Fei Ai Za Zhi 1: 92-94.

26  Guliang  H,  Tefu  L  (1999)  Mycobacterium  tuberculosis  L-forms. Microb Ecol Health Dis 10: 129-133.

27  Xie J, Anchao W, Xiazhi Z (1999) Isolation of acid fast bacillus L- forms from carcinoma of Lung. Acta Academiae Medicinae Bengbu 24: 145-146.

28 Song LY, Yan WS, Zhao T (2002) Detection of Mycobacterium tuberculosis in lung cancer tissue by indirect in situ nested PCR. Di Yi Jun Yi Da Xue Xue Bao 22: 992-993.

29 Yesong WXQ , Lifa X (2004)   A case report on pneumoconiotu- berculosis complicated with lung cancer and   Mycobacterium tuberculosis- L form infection. Chin J Industrial Med.

30 Zhang  S,  Guang-ling  Z,  Yan-sheng  T  (2009)  Detection  of Mycobacterium tuberculosis L forms infection in tissues of lung carcinoma. Chin J Public Health 25: 1317-1318.

31 Yang B, Tian Y, Cui X, Zhang W, Ma Y et al. Detection of Mycobacterium tuberculosis L-forms and MPB64 in breast cancer tissues The Journal of Practical Medicine. 2013; 29(15) p2552-2555.

32  Sheng TY, Kun CX, Tong H, Guang LH, Wei Z, et al. (2009) Study on the relationship between Mycobacterium tuberculosis L infection and lung cancer. Tumor 29: 1085-1089.

33  Tian Y, Hao T, Cao B, Zhang W, Ma Y, et al. (2015) Clinical End-Points Associated with Mycobacterium tuberculosis and Lung Cancer: Implications into Host- Pathogen Interaction and    Coevolution. Bio Med Research Intern p: 9.

34 Alexander-Jackson E (1970) Ultraviolet spectrogramic microscope studies of Rous sarcoma virus cultured in cell-free medium. Ann N Y Acad Sci 174: 765-781.

35  Van der Maaten M, Miller J (1976) Replication of bovine leukemia virus in monolayer cell cultures. Bibl Haemat 43: 360-362.

36  Lysenko  AP,  Drogun  AG,  Shurinova  (1998)  Studies  of  influence atypical mycobacterial  infection on AGID results with sera of cattle infected BLV (in Russian). Vet. nauka – proizvodstvu 33: 56-54.

37  ShivRaj L, Patil SA, Girdhar A, Sengupta U, Desikan KV, et al. (1988) Antibodies to HIV-1 in sera from patients with mycobacterial infections. Int J Leprosy 56: 546-551.

38 Lysenko AP, Vlasenko AP, Broxmeyer L (2014) Phenomenon of variability of mycobacteria and its use for detection of a tuberculosis infection.

39 Lysenko AP, Vlasenko VV, Broxmeyer L, Lemish AP, Novik TP, et al. (2014) The tuberculin skin test: how safe is safe?  The tuberculins contain unknown forms capable of reverting to cell-wall deficient mycobacteria. Clin Exp Med Sci 2: 55-73.

40  Lysenko AP, Vlasenko VV, Lemish AP (2014) Detection of mycobacteria in tissues by means of the differentiating immunoperoxidase staining. Tuberculos i bolezni legkhih 10: 55-58.

41  Duesberg PH (1987)  Retroviruses  as carcinogens and pathogens: expectations and reality. Cancer Res 47: 1199-220.

42  Demochowski L, Grey CE (1957) Subcellular Structures of Possible Viral Origin in Some Mammalian Tumors. Ann NY Acad Sci : pp 559-615

43 Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685.

44  Dameshek W and Gunz (1965) Leukemia. Am J Med Sci 249: 115.

45 Seibert  FB,  Feldmann  PM,  Davis  RL,  Richmond  IS  (1970) Morphological, Biological, and Immunological Studies on Isolates from Tumors and Leukemic Bloods. Ann NY Acad Sci 174: 690-728.

46 Mankiewicz E (1965) Bacteriophages that lyse mycobacteria and corynebacteria, and show cytopathogenic effect on tissue cultures of renal cells of cercopithecus aethiops: a preliminary communication. Can Med Assoc J 92: 31-33.

47  Seibert FB (1968) Pebbles on the hill of a scientist. St Petersburg Printing Company 1: 162.

48 Dobrindt U, Reidl J (2000) Pathogenicity islands and phage conversion: evolutionary aspects of bacterial pathogenesis. Int J Med Microbiol 290: 519-27.

49 Landman OE, Burchard WK, Angelety LH (1962) Lysogeny and bacteriophage adsorption in stable and reverting L-forms of Salmonella paratyphi B and Escherichia coli. Bacteriol Proc p: 53.

50  Falagas ME, Kouranos VD, Athanassa Z, Kopterides P (2010) Review ―Tuberculosis and malignancy. Q J Med 103: 461-487.

51  Nelson EL, Pickett MJ (1951) The Recovery of L Forms of Brucella and their Relation to Brucella Phage. J Infect Dis 89: 226-32.

52  Kruegar AP, Cohn T, Smith PN, McGuire CD (1948) J Gen Physiol 31: 477-488.

53 Takahashi S (1979) L phase growth of Mycobacteria. 1. Cell wall deficient form of Mycobacteria. Kekkaku 54: 63-70.

54  Broxmeyer L, Sosnowska  D,  Miltner E, Chacón O, Wagner D, et al. (2002) Killing of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens. J Infect Dis 186: 1155-60.

55 Devadoss PO, Klegerman ME, Groves MJ (1993) Phagocytosis of Mycobacterium bovis BCG organisms by murine S180 sarcoma cells. Cytobios 74: 49-58.

56 Marcova N, Michailova L, Kussovsski V, Jordanova M (2008) Formation of persisting Cell Wall Deficient Forms M. bovis BCG during interaction with peritoneal macrophages in guinea pigs. Electronic J. of Biology 4: 1-10.

57  Chauhan A, Madiraju MV, Fol M, Lofton H, Maloney E, et al. (2006) Mycobacterium tuberculosis Cells Growing in Macrophages Are Filamentous and Deficient in FtsZ Rings. J Bacteriol 188: 1856-1865

58  Wagner PL, Waldor MK (2002) Bacteriophage Control of Bacterial Virulence. Infect Immun 70: 3985-3993.

 

 

 

RENSE.COM: EBOLA vs African TB ― OR HOW TO HIDE A DIAGNOSIS BEHIND A FEVER

November 20, 2014

 Dr. Lawrence Broxmeyer, MD

 

The CDC has quietly lowered its “critical temperature” protocols for detecting a fever ‘characteristic’ for Ebola after one health care worker slid by with a low-grade fever ― yet tested Ebola positive ― So……
“We changed to 100.4 after the first nurse presented to hospital with symptoms of disease and her temp was not the 101.5 that Ebola patients usually present when they are having vomiting diarrhea, etcetera,” CDC spokesman Thomas Skinner told the Daily Caller.
Etcetera. Etcetera. What Skinner meant is their Ebola temperature criteria has been changed to a temperature of 100.4ºF or above.
Anyway 100.4° (or above) sounds like a nice round number. So let’s examine it.
On the National Health Service’s website, put up by the UK government, the now magically designated temperature of100.4ºF or above also appears ― but not for Ebola. They are describing temperatures characteristic for tuberculosis. (http://www.nhs.uk/Conditions/Tuberculosis/Pages/Symptoms.aspx)

And, it might be added, temperatures characteristic for a dozen-and-a-half other illnesses.
So much for the use of temperature as an Ebola criteria.

Subsequently, by October the 20th ― World Health Organization (WHO) claimed Nigeria, which used to have the highest ‘Ebola’ death rate of any country in the world (See: http://rense.com/general96/ebooraf.html – “Ebola-free” Great, but does that they can say the same about the Ebola-like symptoms originating from the African strains of tuberculosis ― namely Mycobacterium tuberculosis and Mycobacterium africanum ― still raging over there? Will they next proclaim West Africa “Tuberculosis-free?”

Extrapulmonary (outside of the lungs) tuberculosis is the most frequent cause of a prolonged Fever of Unknown Origin (FUO) and has been for a long, long time.1,2
And in patients returning from areas where tuberculosis and malaria are
Common ― such as Africa ― the index of suspicion for these diseases should be elevated.
The current question………………… is it?
REFERENCES:

1. Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Casademont J. Harrison’s Principles of Internal Medicine. 16th Edition. 2004. McGraw-Hill Professional Publishing. 2680 pp
2. Roth AR, Basello GM. Approach to the adult patient with fever of unknown origin.Am Fam Physician. 2003 Dec 1;68(11):2223-8.

See also:

http://www.rense.com/general96/ebotbinter.html  Ebola & African TB – An Interview With Dr. Lawrence Broxmeyer, MD Part 1  Jeff Rense Dr. Lawrence Broxmeyer, MD 11-6-14
http://www.rense.com/general96/eboaf2.html
Ebola & African TB – An Interview With Dr. Lawrence Broxmeyer, MD Part 2
http://www.rense.com/general96/ebolareal.html
Is The Ebola Virus Real? From Dr. Lawrence Broxmeyer, M.D. © U.S. Library of Congress All rights reserved 11-9-14

Vitamin C and Its Unauthorized High-Dose Use for Ebola

November 4, 2014

Dr. Lawrence Broxmeyer, MD

 

© U.S. Library of Congress. All rights reserved. November 1, 2014

 

grayscale

Vitamin C is at present untested and unapproved for treatment of the current Ebola virus outbreak. Yet its mention by many, as in past outbreaks and epidemics, is predictably being brought up. A bleeding tendency in both severe lack of Vitamin C and in Ebola is cited. Vitamin C, in moderation, is essential to our good health ― the key word being moderation. Curiously, in the current atmosphere, many believe that if Vitamin C is working to relieve a patient’s symptoms, then it must be a “virus” that it is working against ― despite repeated assurance in the literature that a “viral-like” illness does not mean a viral-caused illness. Perhaps some Vitamin C history is in order.

In 1976, two-time Nobel laureate Linus Pauling, tempered by his 1971 publication Vitamin C and the Common Cold1, published a similar sounding title ― Vitamin C. the Common Cold, and the Flu.2 And, at the same time, Pauling tossed his hat into the cancer arena by co-authoring a study regarding Vitamin C and cancer. Entitled Supplemental Ascorbate (Vitamin C) in the Supportive Treatment of Cancer, it was written with a medical doctor (Pauling was a PhD) from Scotland named Ewan Cameron.3 In the study 100 “terminal” cancer patients were treated with mega-dose 10-Grams-per-day quantities, divided throughout the day. Their results soon showed that Vitamin C helped with cancer, but not in convincing the medical establishment ― and a swirl of controversy like none he had experienced surrounded Linus Pauling.

The study, performed in Scotland, a country with an extremely high cancer rate reported that while 22% of cancer patients taking these huge doses of Vitamin C survived for more than a year after being labeled terminal ― only 0.4% of similar patients during that same time survived without the Vitamin. On average cancer patients taking the Vitamin C survived 4 times longer ― but in most cases this could be measured in days or months.

Pauling wanted the National Cancer Institute (NCI) to let him repeat the study in the US, but instead the NCI chose scientists at the Mayo Clinic. Results there under E.T. Creagan showed little going for the use of high dose Vitamin C in cancer.4 Pauling immediately objected on the grounds that most of the Mayo patients had received chemo and radiation, which weakened the very immune system needed for Vitamin C to be effective. This led to a repeat trial headed by Creagan’s second-in-command at Mayo, Charles Moertel, whose results led him again5 to denounce the use of megadose Vitamin C in advanced cancer ― even in patients with no prior chemotherapy.

This time Pauling and Cameron bounced back by saying that even this second study fell short as the vitamin was stopped prematurely if there were signs it wasn’t working. (Cameron and Pauling had continued Vitamin C indefinitely throughout their study). Also they criticized the Mayo study regarding the rebound effect that this could lead to and for not taking routine urine tests for Vitamin C prior to beginning the trial to make sure that control patients weren’t taking Vitamin C independent of the study. The controversy continued to swirl.

Actually Linus Pauling’s interest in Vitamin C grew from the research of biochemist Irwin Stone. Stone6 would eventually publish The Healing Factor: “Vitamin C” Against Disease. In the book Stone related that thru a mutation which occurred long ago man could not manufacture Vitamin C in his body.

This was a serious change, since organisms who can’t manufacture ascorbic acid (Vitamin C) were in danger of extinction. Stone placed this mutation as having occurred 55 to 65 million years ago.Ibid Scurvy, the disease resulting from too little Vitamin C could and would result.

 

 

Vitamin C

Stone’s popular book “The Healing Factor: Vitamin C Against Disease” – with a Forward from Linus Pauling, who Irwin Stone Inspired To Go On To do Vitamin C Research. Stone’s Cover Caption rightfully begins with: “Vitamin C may save your life!”

 

 

Daily Vitamin C – Necessary in Every Way

 

Stone captured that lack of Vitamin C could present as everything from a mild “not feeling right” to much, much more serious events called acute scurvy. The latter began with change of complexion (pale or muddy), loss of accustomed vigor, quick tiring, breathlessness and a desire for sleep, but progressed in severity to fleeting limb and joint pains, sore and bleeding gums, and small reddish spots (representing hemorrhaging), especially on leg hair follicles progressing at times to nosebleeds and blood in the urine. As the disease called scurvy advanced, teeth become loose and bones become so brittle that they could be broken by merely moving in bed. The body’s joints in the end became so damaged that the noise from the bones grinding upon on another could actually be heard as a rattling noise ― and death came by either sudden collapse on mild exertion or from secondary infection such as pneumonia.Ibid

 

 

Scurvy, a disease of significant Vitamin C deficiency becomes rapidly noticeable. Among its signs and symptoms are weakness, anemia, bruising, bleeding gums and loose teeth.

Scurvy, a disease of significant Vitamin C deficiency becomes rapidly noticeable. Among its signs and symptoms are weakness, anemia, bruising, bleeding gums and loose teeth.

 

 

For millennia, Stone said, man has suffered from lack of Vitamin C, and when the Hungarian Szent-Györgyi isolated it at Cambridge in 1928 and proved his findings in 1931, others were free to derive its chemical structure and produce it synthetically. Albert Szent-Györgyi came away with a Nobel Prize ― in research that began about as unexpectedly as Fleming’s find of penicillin.7

 

 

 

Chemical Formula of Vitamin C. Thanks to Szent-Gyorgyi, this Compound was Isolated and Could be Mass Produced.

Chemical Formula of Vitamin C. Thanks to Szent-Gyorgyi, this Compound was Isolated and Could be Mass Produced.

 

 

In The Healing Factor, Stone underscored that Vitamin C cannot adequately be stored. Therefore man needed to constantly replenish it through foods rich in Vitamin C. He felt the daily Vitamin C (ascorbic acid) recommended by the National Research Council of 60 mg. daily was woefully inadequate ― citing many scientists and doctors who agreed with him. Szent-Gyorgyi was among them, feeling that “the daily dosage of ascorbic acid should be much higher.”

By 1969, Stone had documented laboratory tests conducted at the National Cancer Institute which showed that ascorbic acid was lethal to certain cancer cells and harmless to normal tissue. This was all being carefully monitored by Dr. Virginia Livingston’s group at Rutgers’s ― which was at the time pulling in sizable grants from major corporations in her quest to prove that cancer was from a tubercular-like cancer germ, which stained acid-fast (as opposed to other microbes) and appeared routinely as the cause of cancer in both her laboratory animals and biopsied human tissue specimens.8

But after the discovery and isolation of Vitamin C in 1928, and the establishment of its underlying relationship to scurvy, the declining incidence of this disease has led to complacency, scurvy being thought of as a well-nigh extinct disease. All of this has resulted in failure to recognize and treat subclinical forms of this disease and its complicated relationship to other disease. Scurvy and its bleeding tendencies were caused by lack of Vitamin C of course. Why go further?

 

 

A Germ With “Particular Sensitivity” to Destruction Through Vitamin C

 

But actually the antiseptic and bacterial qualities of ascorbic acid have long been known and mycobacteria such as TB are heavily influenced by them. Moreover there began to appear laboratory proof that TB itself depleted Vitamin C levels badly and could in itself cause subclinical scurvy. According to Stone:
“The bacteria causing tuberculosis (Mycobacteria tuberculosis) is particularly sensitive to the lethal action of ascorbic acid”.Op.cit.

Two decades before its discovery and isolation, said Stone, ascorbic acid’s effect on mycobacteria such as tuberculosis began to seep into the literature empirically. As early as 1933, McConkey and Smith9 took guinea pigs fed tuberculous sputum daily and split them into two groups. The first group was subjected to a Vitamin C deficient diet, while the second group, fed two teaspoonfuls of Vitamin C rich tomato juice, completed the study. McConkey’s idea came from his clinical observation that patients hospitalized with the intestinal form of the tubercular disease, some of which were hemorrhaging, improved when tomato juice was added to their menu. In the Vitamin C deficient cohort group 26 of the animals died from intestinal ulcerations, while only 2 succumbed while taking tomato juice ― despite the small amounts (2mg) daily. This is what Stone meant when he said that TB was “particularly sensitive” to the lethal action of ascorbic acid.

McConkey’s work was confirmed by de Savitch10 ― with orange juice as the Vitamin’s source (deSavitsch et al.1934) and Birkhaug in 193811 ― both studies using what Stone felt were woefully inadequate amounts of C. Birkhaug was on to something quite important. Not only did Vitamin C protect against “the initial invasive onslaught of”Ibid progressive tubercular disease ― but the disease itself was depleting Vitamin C levels in the body.

Actually, such linkage of TB to scurvy, historically, was nothing new. No later than in 1689 did Richard Morton, one of the earliest writers on scurvy, mention in Phthisiologia, a book which gained him almost a century of fame, say:
“Scurvy is wont [accustomed] to occasion a consumption [tuberculosis] of the lungs.”12

Birkhagh though, was essentially saying that tubercular disease caused subclinical scurvy, mentioning:
“Our study has shown that by compensating for the inevitable state of hypovitaminosis [too little] C which occurs in progressive tuberculosis, we render the animal organism more resistant against the inflammatory-necrotizing effect of tuberculosis and the initial invasive onslaught of virulent tubercle bacilli.” (Birkhaug, 1938). But what Birkhaug was not picking up, according to Erwin Stone, was that that Vitamin C was drop-dead lethal to tuberculosis.

Like Birkhaugh, Andosca and Foley13 realized that tuberculosis itself created Vitamin C deficiency. Andosca: “Most authors maintain that there is a deficiency of vitamin C in tuberculous patients.” Faulkner and Taylor14, for example, disclosed an increased demand for Vitamin C with infection. Patients with tuberculosis required more than 200 mg. of ascorbic acid a day to keep the plasma level normal.

Subclinical Scurvy from TB

Bauer and Vorwerk15 found vitamin C deficiencies of from 1 to 4 grams in the tubercular, finding a direct parallel between the activity of tuberculosis and the extent of vitamin C deficiency. Borsalino16 reported a study of 140 tuberculosis patients, in which administration of vitamin C rapidly increased capillary resistance and stopped hemoptysis ― the spitting up of blood or blood-tinged sputum. However such blood loss reappeared when treatment was discontinued. By 1946, in a survey of nutrition among the northern Manitoba Indians, Moore et al17 reported a very high mortality rate from tuberculosis and pneumonia among these Canadian Indians ― which they attributed to a diet extremely low in Vitamin C.

As Irwin Stone pointed out, “There were many more reports in this sickening mass of continued repetition of ineffectual clinical tests where the investigators were correcting a nutritional deficiency instead of using ascorbic acid to actually combat the disease.”ibid In the meantime, the extent of Vitamin C deficiency or hypovitaminosis documented by Birkhaug with mycobacterial disease was soon realized to be equivalent in cancer, still another similarity in the two wasting diseases. (Carneron & Pauling, 1979)

Further positive animal studies that Vitamin C was a potent anti-tubercular were run separately by Kleimenhagen, Steinbach, and Boyden.18,19,20 culminating with Getz’s study21 of over 1000 men which intimated that were there were adequate Vitamin C blood levels ― there was no Mycobacteria tuberculosis. Still, persisted Stone: “The dogma of the vitamin theory kept these clinicians from thinking of ascorbic acid as an antibiotic and using it in the necessary antibiotic dosages.”ibid

That was until Charpy’s 1948 study22, in which a truly massive l5 Grams or 15,000 milligrams a day were given to terminal consumptive patients. These tubercular patients were so gone that one of them died before the study got underway, but the others survived and improved strikingly despite the fact that they seemed in Charpy’s words: “unaware of the enormous tuberculosis lesions they harbored”, a situation apparently again found analogous in studies of Vitamin C and cancer. Charpy does not go into possible toxicity of such high Vitamin C, nor the kidney stones that could result from it. Vitorero and Doyle23, on the other hand, found excellent results in the treatment of intestinal TB merely by injecting 500 to 600 milligrams of ascorbic acid a day initially, which was reduced to 400 milligrams as improvement was shown, and then further reduced to 200 milligrams a day. Vitorero and Doyle were quite positive about the benefits of this treatment in their few cases and recommended its use for intestinal tuberculosis.

Fast Forward to 2013

In her cancer diet, physician Virginia Livingston Op. cit used vitamins which included Vitamin C to combat her modified mycobacterial cancer germ, but not nearly to the extent of the high doses suggested by Pauling and others. But just how well Vitamin C, at the proper concentration killed even drug resistant TB had to wait until 2013.24

In an unexpected discovery, researchers at Albert Einstein College of Medicine determined that Vitamin C, all by itself, killed both TB and drug resistant TB on culture plates. The finding suggested that Vitamin C, added to existing TB drugs could enhance and possibly shorten TB therapy. The study was published in the online journal Nature Communications.

The molecular mechanism by which vitamin C exerted its lethal effect was that Vitamin C induced what is known as a Fenton reaction, causing iron to react with other molecules to create reactive oxygen species (ROS) that kill the TB (Mtb) mycobacteria.

Peculiar and Unique to TB above other microbes, Vitamin C -Through a Fenton reaction - Kills Tuberculosis (Mtb) by Causing Iron (Fe) to Create Reactive Oxygen Species (ROS) - Which Destroy Even Drug Resistant Strains of TB.

Peculiar and Unique to TB above other microbes, Vitamin C -Through a Fenton reaction – Kills Tuberculosis (Mtb) by Causing Iron (Fe) to Create Reactive Oxygen Species (ROS) – Which Destroy Even Drug Resistant Strains of TB.

What Irwin Stone had so long ago said and predicted ― that TB was “particularly sensitive” to Vitamin C ― was now recognized scientific reality.

 

REFERENCES

1. Pauling, Linus. Vitamin C and the Common Cold. Bantam Books. New York. 1971.112pp.
2. Pauling, Linus. Vitamin C, the Common Cold, and the Flu. W.H. Freeman and Company. San Francisco. 1976.230pp
3. Pauling and Cameron, 1976). Pauling, Linus and Cameron, Ewan. Supplemental Ascorbate in the Supportive Treatment of Cancer. Proceedings of the National Academy of Sciences, Vol.73: pp.3685-89. 1976.
4. Creagan ET, Moertel CG et al.Failure of high-dose vitamin C (ascorbic a N Engl J Med1979 Sep 27;301(13):687-90) therapy to benefit patients with advanced cancer. A controlled trial.
5. Moertel CG, Fleming TR, Creagan ET, Rubin J, O’Connell MJ, Ames MM. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl. J Med. 1985 Jan 17; 312(3):137-41)
6. Stone, Irwin. The Healing Factor- “Vitamin C” Against Disease. Grosset & Dunlap Publishers. New York. 1972.)
7. Kyle, R. A.; Shampo, M. A. (2000). “Albert Szent-Györgyi–Nobel laureate”. Mayo Clinic proceedings. Mayo Clinic 75 (7): 722
8. Livingston-Wheeler V, Addeo EG. The conquest of cancer. CreateSpace Independent Publishing Platform. January 30, 2013. Pp. 288.
9. McConkey, M. and D.T. Smith. The Relation of Vitamin C Deficiency to Intestinal Tuberculosis in the Guinea Pig. Journal of Experimental Medicine. Vol.58: pp. 503-12. 1933.
10. De Savitsch, et al. The Influence of Orange Juice on Experimental Tuberculosis in Guinea Pigs. National Tuberculosis Association Transactions. Vol. 30 pp. 130-135. 1934.
11. Birkhaug, K.E.. The Role of Vitamin C in the Pathogenesis of Tuberculosis in the Guinea Pig. I to V. Acta Tubeculosis Scandinavica, Vol 12: pp. 89-98, 98-104, 359-372. 1938.
12. Morton, R. Phthisiologia, seu, Exercitationes de phthisi tribus libris comprehensae totumque opus variis historiis illustratum . Latin Edition. EEBO Editions, ProQuest Publishers. (Latin) Paperback – January 3, 2011. 444pp 1689.
13. Andosca JB, Foley JA. Calcium Ribonate and Vitamin C (Nu 240-10) in the Treatment of Tuberculosis Chest.1948;14(1):107-114. p.109.
14. Faulkner J, Taylor F. Vitamin C and Infection: Ann. Int. Med.. 10:1867. 1931.
15. (Baur and Vorwerk. “Beitrag sum Vitamin C Deficit bei Lungentuberculosen.” Beitr. S. Tuberk., 91: 262, 1938)
16. Borsalino, G. “Fragilite Capillare nella Tuberculose Polmonare e le sue Modificazione par azione della vitamin C.” Gior. de clin. Med., 18: 273, 1931.
17. Moore, et al. “Nutrition among Northern Manitoba Indians.” Can. Med. Assoc. J., 54: 223, 1946.
18. Kleimenhagen, P.. Effect of Ascorbic Acid on Experimental Tuberculosis in Guinea Pigs. Zeitschrift fur Vitaminforschung. Vol 11: 209-227. 1941.
19. Steinbach, M. M. and Klein, S.J. Vitamin C in Experimental Tuberculosis in Guinea Pigs. American Review of Tuberculosis. Vol 43: 403-13. 1941.
20. (Boyden, SV, Anderson, ME. Diet and Experimental Tuberculosis in the Guinea Pig. Acta Pathologica et Microbiologica Scandinavia (Kobenhavn). Vol. 39: 107-16. 1956.
21. Getz, 1951). (Getz, HA, Henderson HJ. A Study of the Relation of Nutrition to the Development of Tuberculosis; influence of ascorbic acid and vitamin A. Am Rev Tuberc. 1951 Oct; 64(4):381–393.
22. Charpy, J., and Ascorbic Acid in Very Large Doses Alone or with Vitamin D in Tuberculosis. Bulletin de I’Academie Nationale de Medicine (Paris). Vol. 83:421-3. 1948.
23. Vitorero, JRB, Doyle, J. Treatment of intestinal tuberculosis with vitamin C, Med. Wkly., 2, 636, 1938
24. Vilchèze C, Hartman T, Weinrick B, Jacobs WR Jr. Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction. Nat Commun. 2013, May;4:1881. 23 pp.

© U.S. Library of Congress
All rights reserved
November 1, 2014

SEE also: http://preview.tinyurl.com/mowcz2c