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Is it possible to die of an undiagnosed infection?
May 17, 2008

According to the Armed forces of Pathology it is.

Lo SC; Dawson MS; Newton PB 3rd; Sonoda MA; Shih JW; Engler WF; Wang RY; Wear DJ. Association of the virus-like infectious agent originally reported in patients with AIDS with acute fatal disease in previously healthy non-AIDS patients. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, September 1989, volume 41, number 3, pages 364-376.

EXAMPLE 21 M. fermentans incognitus Identified In Non-AIDS Patients Six patients from six different geographic areas who presented with acute flu-like ilnesses were studied. The patients developed persistent fevers, lymphadenopathy or diarrhea, pneumonia, and/or heart, liver, or adrenal failure. They all died in 1-7 weeks. These patients had no serological evidence of HIV infection and could not be classified as AIDS patients according to CDC criteria. The clinical signs as well as laboratory and pathological studies of these patients suggested an active infectious process, although no etiological agent was found despite extensive infectious disease work-ups during their hospitalization. Post-mortem examinations showed histopathological lesions of fulminant necrosis involving the lymph nodes, spleen, lungs, liver, adrenal glands, heart, and/or brain. No viral inclusion cells, bacteria, fungi, or parasites could be identified in these tissues using special tissue stains. However, the use of rabbit antiserum and the monoclonal antibodies raised against M. fermentans incognitus (Example 8), the pathogen shown to cause fatal systemic infection in primates (Example 10), revealed M. fermentans incognitus antigens in these necrotizing lesions. In situ hybridization using a .sup.35 S labeled M. fermentans incognitus-specific DNA probe (Example 18) also detected M. fermentans incognitus genetic material in the areas of necrosis. Furthermore, M. fermentans incognitus particles were identified ultrastructurally in these histopathological lesions. M. fermentans incognitus was associated with the systemic necrotizing lesions in these previously healthly non-AIDS patients with an acute fatal disease. Typical areas of necrosis due to the M. fermentans incognitus infection of these patients are shown in FIG. 21. Most of the tissues which had massive necrosis showed only minimal lymphocytic or histiocytic response and few neutrophils (FIGS. 21A, B and C). FIG. 21A is a photomicrograph of splenic tissue (x 30.5). FIG. 21B shows the peripheral margin of necrosis of 21A (x 153). FIG. 21C is a photomicrograph of lymph node tissue (x 15.25). Occasionally, a chronic or acute inflammatory reaction could be identified in the areas of necrosis (FIG. 21D). FIG. 21D is a photomicrograph of adrenal gland tissue (x 153). Representative samples of the immunostained tissues of these patients are shown in FIGS. 22A-D. FIG. 22A is a photomicrograph of spleen tissue (x 80). FIG. 22B is a higher magnification of the margin of necrosis of 22A (x 353). FIG. 22C is a photomicrograph of lymph node tissue (x 257). FIG. 22D is a higher magnification of cells with positive cytoplasmic staining of 22C (x 706). FIG. 22E is a photomicrograph of hemorrhagic necrosis in adrenal gland tissue (x 706). The areas which displayed the highest concentration of M. fermentans incognitus related antigens were often at the margin of necrosis. However, the necrotic center and peripheral unaffected areas had relatively low reactivity. Most of the positively stained cells were identified as lymphocytes or histiocytes in the lymph nodes and spleen, or reactive mononuclear cells in the liver, lungs, adrenal glands and heart. Immunostaining of control tissues with necrotizing lesions from patients with cat scratch disease, Hodgkin's disease, malignant lymphoma, cryptococcal fungal infections and hemorrhagic splenic tissues of Hairy cell leukemia did not display a positive reaction. Serum obtained from the same rabbit before immunizaiton with M. fermentans incognitus antigens also failed to display a positive immunoreaction in the necrotizing lesions of the six patients. Using a .sup.35 S radiolabeled psb-2.2 M. fermentans incognitus DNA probe (Example 18), strong labeling of clusters of cells at the margins of necrosis of the affected tissues was observed. The affected tissues tested were formalin-fixed, paraffin-embedded spleen, lung, lymph node, adrenal gland liver and bone marrow. The intensity of the labeling, or the number of grains localized in the cells at the margin of necrosis was well above the level present at either the necrosis (FIGS. 23A and B). However, there were also clusters of apparently viable cells in the necrosis which were also strongly labeled (FIG. 23C). FIG. 23A shows strong labeling of cells at the peripheral zone of necrosis (x 76.5). FIG. 23B is a higher magnification of 23A (x 422). FIG. 23C shows the occasional positive labeling in an area of diffuse necrosis in the spleen (x 150). The inset of 23C is a higher magnification (x 422). Formalin-fixed, paraffin-embedded liver and spleen tissues from a patient with pancreatic carcinoma were used as negative controls, and showed no labeling above background levels. A control probe of .sup.35 S labeled cloning vector DNA, not containing psb-2.2 M. fermentans incognitus DNA did not label any of the tested tissues (FIG. 23D). FIG. 23D is the same area of FIG. 23C in the consecutive tissue section, hybridized with .sup.35 S labeled cloning vector DNA not containing psb-2.2 M. fermentans incognitus DNA (x 150) (i.e., control for 23C). Areas of the necrotizing lesions which immunostained most positively for M. fermentans incognitus specific antigens were examined by electromicroscopy. Particles with characteristic ultrastructural features of M. fermentans incognitus were directly identified in all the lesions. These particles in the areas of necrosis, morphologically resembled M. fermentans incognitus previously identified in Sb51 cells (Example 4) and in the tissues of experimentally inoculated monkeys (Example 10). The particles were heterogeneous in size and shape, with most particles being spherical and about 140 to 280 nm in diameter. At the margin of necrosis, the M. fermentans incognitus particles were located in the cytoplasm of cells with apparently no cytopathic changes, or in fragments of cytoplasm from completely disrupted cells (FIG. 24). FIG. 24 shows electron mircographs of tissues derived from areas highly positive for M. fermentans incognitus-specific antigens. FIG. 24A is an electron micrograph at a margin of necrosis in adrenal gland tissues (Bar=1,000 nm). FIG. 24A.sub.2 is a higher magnification of 24A (Bar=100 nm). FIGS. 24B.sub.1, and B.sub.2 are electron micrographs of the peripheral zone of necrosis in lymph node tissue (Bar=1,000 nm). FIG. 24B.sub.3 is a higher magnification of 24B.sub.2 (Bar=100 nm). Table 5, below, summarizes the profiles and histopathological findings for each of the six patients. TABLE 5 __________________________________________________________________________ Summary of Patient's Profiles and Histopathological Findings Tissue with necrotic Duration lesions identified Personal Salient clinical of illness by biopsy or at Patient Profiles presentation (weeks) autopsy __________________________________________________________________________ 1 29-year old arthralgia, myalgia, conjunc- 4.5 spleen, lung black man tivitis, persistent fever, hypercalcemia, liver failure (late), ARDs* (late) 2 33-year old persistent fever, diarrhea, 7 lymph nodes, liver, white woman generalized lymphadenopathy, spleen, kidneys abnormal liver functions, seizure (late) 3 40-year old arthralgia, myalgia, sore 3.5 adrenal glands white man throat, chest pain, persis- (bilateral), heart, tent fever, malaise, diarrhea, brain finger numbness, comatose (late) 4 31-year old vomiting and diarrhea, tremor, 1.5 liver, spleen black woman fever, epigastric and chest pain, abnormal liver functions, headache 5 23-year old Watery diarrhea, vomiting, 3 liver, heart white man jaundice, arthralgia, myalgia 6 33-year old fever, malaise, nausea and 1 spleen, liver black man vomiting, myalgia and weakness, liver failure and jaundice, confusion and hallucinations (late) __________________________________________________________________________ *ARDS Adult Respiratory Distress Syndrome

Lo SC; Dawson MS; Newton PB 3rd; Sonoda MA; Shih JW; Engler WF; Wang RY; Wear DJ. Association of the virus-like infectious agent originally reported in patients with AIDS with acute fatal disease in previously healthy non-AIDS patients. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, September 1989, volume 41, number 3, pages 364-376.

ATN) MYCOPLASMA INCOGNITUS: Newly Discovered Treatable Infection?

AIDS TREATMENT NEWS No. 095 - January 26, 1990

John S. James

--------------------------------------------------------------------------------

Researchers at the U. S. Armed Forces Institute of Pathology (AFIP) in Washington, D. C., and the Warren Grant Magnuson Clinical Center at the National Institutes of Health, have found compelling evidence that a previously unrecognized infection -- one potentially treatable with antibiotics -- may be a major cause of illness in people with AIDS and might play a role in many other illnesses. Many infections of organs including the brain, spleen, liver, or lymph nodes -- as well as some systemic infections -- might be caused by the newly-discovered organism, called Mycoplasma incognitus. Until now, these infections would be counted among the many which cannot be diagnosed.

While the first report of the organism now known as Mycoplasma incognitus was published over three years ago, most of what is now known was learned later and published last year. And only in the last few weeks has the AIDS research community paid serious attention. Until recently the new organism was mistakenly believed to be a virus, and its discovery seemed to have little immediate relevance to treatment.

Then a series of five articles by Armed forces Institute of Pathology chief Shyh-Ching Lo M.D PH.D and others in the American Journal of Tropical Medicine and Hygiene, between February and November 1989, showed:

(1) The new organism is a mycoplasma -- which is potentially treatable. Mycoplasma, a form of life between bacteria and viruses in complexity, was discovered about 100 years ago. Some species are known to cause human diseases.

The published articles only hint that the new organism might be treatable with antibiotics. But scientists at AFIP tested 15 common antibiotics against the Mycoplasma incognitus in the laboratory. A detailed report is being prepared for publication, but because of the public-health importance of the information, AFIP released a list of the drugs and their effective concentrations in a separate document. Doxycycline, tetracycline, clindamycin, lincomycin, and ciprofloxacin were found to be effective against Mycoplasma incognitus. But erythromycin, the antibiotic most commonly used to treat mycoplasma infections, was not effective -- and penicillin, streptomycin, gentamicin, and others also had no effect.

(2) Mycoplasma incognitus was found in the thymus, liver, spleen, lymph node, or brain of 22 of 34 persons who had died of AIDS. The patients who were selected for this autopsy study had all had evidence of organ failures.

(3) In a separate study with different patients, the mycoplasma was found in seven of ten persons with AIDS. Also, a much earlier study had found Mycoplasma incognitus in blood lymphocytes of 12 of 23 living persons with AIDS -- but in none of 22 healthy blood donors used as controls.

(4) The mycoplasma was also found in six HIV-negative patients (with no sign of AIDS) from different parts of the world, who had died in one to seven weeks of an undiagnosed infection.

No one knows how the organism spreads, but evidently it is not by casual contact, as family members of infected persons have not become infected themselves.

(5) Four monkeys were injected with Mycoplasma incognitus; all died in seven to nine months. The organism was found in the spleens of all the monkeys, and in some other organs as well. It was not found in a fifth monkey tested as a control.

(6) Extensive evidence from electron-microscope examinations, from specially designed PCR tests to look for the DNA of Mycoplasma incognitus, and from immunologic tests, showed that the organism was concentrated in lesions in affected organs. Mycoplasma incognitus is unusual in that it often infects and kills tissue without causing an inflammatory reaction, suggesting that it disables or evades part of the immune system.

The publication of this evidence, much of it in November 1989, led to a meeting between Dr. Anthony Fauci, director of NIAID (the National Institute of Allergy and Infectious Diseases) and other AIDS experts, with Dr. Lo and his colleagues at AFIP. The meeting, on December 14, 1989 in San Antonio, was chaired by Dr. Joel B. Baseman, chairman of the Department of Microbiology at the University of Texas Health Sciences Center in San Antonio, an expert on mycoplasma. An article in THE WASHINGTON POST (January 5) quoted Dr. Baseman as saying that Lo's mycoplasma "might be a significant agent for many infectious diseases, not just AIDS. There is enough information to say that this agent is real." The same article quoted Dr. Fauci as saying that Mycoplasma incognitus "may be an important opportunistic infection ...If it's real, it could have an important impact on how doctors look at AIDS patients with unexplained problems."

Summary

The organism previously called a "virus-like infectious agent," discovered by Dr. Shyh-Ching Lo and colleagues at the Armed Forces Institute of Pathology, has been found to be a mycoplasma which is susceptible to several common antibiotics. Even before a blood test is widely available and clinical trials have been done, physicians may want to consider this new information when choosing empirical antibiotic treatment for patients with certain undiagnosed problems. We will report further as more information becomes available.

References

Altman LK. Unusual microbe, once dismissed, is now taken more seriously. THE NEW YORK TIMES, January 16, 1990, page B6.

Booth, W; Specter, M. Microbe may play role in AIDS, other diseases. THE WASHINGTON POST, January 5, 1990, page A3.

Lo SC; Dawson MS; Wong DM; Newton PB 3d; Sonoda MA; Engler WF; Wang RY; Shih JW; Alter JH; Wear DJ. Identification of Mycoplasma incognitus infection in patients with AIDS: an immunohistochemical, in situ hybridization and ultrastructural study. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, November 1989, volume 41, number 5, pages 601- 616.

Lo SC; Shih JW; Newton PB 3d; Wong DM; Hayes MM; Benish JR; Wear DJ; Wang RY. Virus-like infectious agent (VLIA) is a novel pathogenic mycoplasma: Mycoplasma incognitus. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, November 1989, volume 41, number 5, pages 586-600.

Lo SC; Dawson MS; Newton PB 3rd; Sonoda MA; Shih JW; Engler WF; Wang RY; Wear DJ. Association of the virus-like infectious agent originally reported in patients with AIDS with acute fatal disease in previously healthy non-AIDS patients. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, September 1989, volume 41, number 3, pages 364-376.

Lo SC; Wang RY; Newton PB 3d; Yang NY; Sonoda MA; Shih JW. Fatal infection of silvered leaf monkeys with a virus-like infectious agent (VLIA) derived from a patient with AIDS. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, April 1989, volume 40, number 4, pages 399-409.

Lo SC; Shih JW; Yang NY; Ou CY; Wang RY. A novel virus-like infectious agent in patients with AIDS. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, February 1989, volume 40, number 2, pages 213-226.

In addition, the NEW YORK NATIVE has published frequent and sometimes controversial coverage of this research.

(The NIH team headed by Dr Joel baseman is sent to examine Loís work.)

ìThe meeting was led by Dr. Joel B. Baseman, a mycoplasma expert at the University of Texas Health Sciences Center at San Antonio. He said the participants were ''very impressed with the quality of science that Dr. Lo's group displayed.''

''The pathology data was solid and convinced us that the agent is in the tissues,'' Dr. Baseman said. The ability of M. incognitus to cause a fatal wasting disease in monkeys and mice persuaded most participants that the microbe ''has the potential to cause disease in humans,''

New York times 1990.

(It could not possibly be a contaminant for Lo saw it by electron microscope in the dying patients tissues, researchers at the U of Alabama confirmed it was a novel strain when they injected rats with it and found it to be highly pathenogenic towards the normal strain of mycoplasma fermentans. Lo went on to inoculate chicken embryos and chimpanzees with M penetrans/incognitus and they all sickened/deformed and died in his publications and patents, itís the only microbe out of HIV, hep c, hpv to cause disease in experimental animals, satisfying Kochís postulates. The Miami Herald contacted Anthony Fauci and asked them why no funding has been provided despite the recommendation by Baseman and his team, Fauci with no explanation told the Miami Herald that he ìwill not discuss Mycoplasma or any other AIDS cofactor.î This is strange for Lo clearly proved it was capable of causing disease and death in hiv negative patients, mice, primates and was not found in one healthy control.)

Garth and Nancy Nicolsonís phdís from the MD cancer center in Texas found the same microbe in CFS/fibromyalgia/GWI. They find that antibody testing is unreliable for the monkeys that Lo inoculated that died only had a weak antibody response when near death, so they use PCR.

ìMycoplasmal infections are associated with several acute and chronic illnesses, including Pneumonia, Asthma, Rheumatoid Arthritis, Immunosuppression Diseases such as AIDS, Genitourinary Infections and Gulf War Illness (GWI). Using forensic Polymerase Chain Reaction blood samples from 132 Chronic Fatigue Syndrome (CFS) (Myalgic Encephalomyelitis ) and/or Fibromyalgia Syndrome (FMS) patients were investigated for the presence of mycoplasmal infections in blood leukocytes. CFS and FMS patients had completely overlapping signs and symptoms and were grouped for purposes of analysis. There was a significant difference between symptomatic CFS/FMS patients with positive mycoplasmal infections (~63%) and healthy positive controls (~9%) (P<0.001). We also examined the incidence of Mycoplasma fermentans infections in these CFS/FMS patients (~50%) and controls (0%)(P<0.001). The prevalence of mycoplasmal infections in female and male symptomatic patients was similar. Similar to GWI patients with mycoplasmal infections (~50%) and with similar signs and symptoms, mycoplasma-positive CFS/FMS patients respond to 6-week cycles of particular antibiotics: doxycycline, minocycline, ciprofloxacin, azithromycin and clarithromycin. Multiple cycles of these antibiotics plus nutritional support appear to be necessary for recovery.î

Garth Nicolson PhD former head of the MD cancer center in Austin.Theyíve written a riveting new book called Project Day Lily in their struggle to help Gulf war vets and sick civilians. www.projectdaylily.com When they found it in the blood of sick gulf war vets they claim armed agents from the Dept. of defense warned them to stop their research, riveting book, rave reviews from several scientists including a noble laureate. They claim it was part of the biological weapons programthis is their true story slightly fictionalized.

You seen the film hiv fact or fraud, pretty interesting, these army scientists and Duesberg were skeptical of HIV causal role. Here is the film. Seems crazy till you see it, here is the link thanks http://video.google.com/videoplay?docid=-8142733917997460212

Response from Dr. Young

Of course it is. Medical science isn't perfect, nor do we know everything.

That said, it's very important to appreciate that case reports in the literature often represent very rare events. A 1989 publication doesn't comprise cutting edge science, does it?

What's your point?

Putting this study (often cited by conspiracy theorists) into the larger context of the world-wide AIDS epidemic is my point. Our forum is about HIV and HIV treatments, not about the entire possibility of medical disorders.

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