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Allen Steere



Allen Steere is a professor of rheumatology at Harvard University and previously Yale University. Steere is largely credited with discovering Lyme disease.

Contents

Discovering Lyme disease

In November of 1975 the Connecticut State Health Department was contacted by two women, Polly Murray and Judith Mensch, who lived in a small town of Lyme, Connecticut, five miles opposite the Plum Island bioweapons lab. Both Murray and Mensch reported that their children had been diagnosed with juvenile rheumatoid arthritis, and each knew of others in the area with similar symptoms.

The Health Department contacted Allen Steere, who was studying rheumatology at Yale University. Steere had also gained some epidemiological experience during a stint at the Epidemic Intelligence Service. [1], a semi-military unit of infectious disease scientists set up in the 1950s to develop offensive biowarfare capabilities.

Mrs. Murray handed Steere a list of dozens of ailing children. He began by calling each family and eventually compiled a list of 39 children. Steere and colleagues identified an additional twelve adults suffering from juvenile rheumatoid arthritis.[2]

A quarter of the people Steere interviewed remembered getting a strange, spreading skin rash (erythema migrans) before experiencing any other symptoms. A European doctor happened to be visiting Yale at the time, and he pointed out that the rash was similar to one frequently encountered in northern Europe and known to be associated with tick bites. Most of the rashes were found somewhere on the torso, suggesting a crawling insect rather than a flying one or a spider, but most patients did not remember being bitten.[3]

In 1976 Steere began testing blood from disease victims for specific antibodies against 38-known tick-transmitted diseases and 178 other arthropod-transmitted viruses. Not one came out positive. When the broader definition of the disease was applied, more cases were discovered, in Connecticut, adjoining states, and the upper Midwest.

Steere then learned about the work of the Swedish dermatologist Arvid Afzelius, who in 1909 had described an expanding, ring-like lesion and speculated that it was caused by the bite of an Ixodes tick. The rash described by Afzelius was later named erythema migrans. Research in Europe had found that erythema migrans and acrodermatitis chronica atrophicans, another rash caused by tics in Europe, responded to penicillin, suggesting that the cause was bacterial, not viral. Yet no microorganisms could be found in fluid from the joints of Lyme disease patients.

The recognition that the patients in the United States had erythema migrans led to the recognition that "Lyme arthritis" was one manifestation of the same tick-borne disease known in Europe.[4] The syndrome first found in and around Lyme and Old Lyme, Connecticut came to be called "Lyme Arthritis" and later "Lyme Disease".[5][6]

In 1980 Steere, et all, began to test antibiotic regimens in adult patients with Lyme disease.[7][8]

Lyme disease controversy

In the realm of Lyme disease few are as influential as Steere. Steere has published almost 200 articles on Lyme Disease between 1977 and 2007.[9]

For his breakthrough work, Steere has been widely heralded. At a ceremony in Hartford, Connecticut in 1998, Gov. John G. Rowland proclaimed Sept. 24 as Allen C. Steere Day.

Steere first published about neurological and cardiac symptoms involved in his early studies of Lyme disease in 1977.[10] Steere first published work about chronic manifestations of the disease in 1979.[11]

By the mid 1990's Steere declared that Lyme disease had become a "junk-drawer diagnosis", covering maladies ranging from chronic fatigue syndrome (CFS), fibromyalgia to hypochondria. To Steere argued that many people receiving antibiotic treatments, especially treatments beyond the recommended four week treatment guideline protocol, "were being done more harm than good".[12]

Writing in The Journal of the American Medical Association (JAMA) in 1993, Steere said the disease was "overdiagnosed" and overtreated.[13] This statement pushed groups of sufferers, scientists and clinicians into squabbling factions and ultimately created the dichotomy which has been termed the Lyme disease controversy. The primary discord arrived over whether the possibility that Lyme disease, in a subset of patients, develops into a chronic disease requiring massive doses of antibiotics over long periods of time.

Steere argued that persisting symptoms may be owing to something he called Post-Lyme syndrome, which is an undefined type of neurological damage and immune-system malfunction resulting from the initial infection. (Steere original termed Post-Lyme syndrome "chronic Lyme disease," leading to confusion about his stance that the chronic Lyme disease, as it means today, has never been demonstrated.[14]) Steere argued patients with a positive serology with symptoms thought to be more defined by CFS or fibromyalgia would not be helped by further antibiotics.[15]

Steere later worked with Frank Dressler; the CDC later adopted their work for its Lyme Disease surveillance case definition. Using primarily sera from early, acute Lyme patients, Steere formulated serodiagnostic criteria for western blotting, a technique which identifies antibodies in the serum directed against foreign antigen, in this case, B. burdorferi, the causative agent of Lyme disease. Steere is criticized for his use as a control a group of mostly sick patients, many of whom had conditions or syndromes which can be confused with post-Lyme symptoms, such as MS or Chronic Fatigue Syndrome.

Some physicians also criticize Steere for choosing to make 20% of his control — 25 serum samples — serum derived from syphilis patients. While this group formed 20% of the control, the disease's annual incidence in the United States is about 3 cases per 100,000 — an incidence of far less, by a multiple of 300, than 1%. This statistical manipulation dramatically impacted the importance of the 41 KdA band on blotting, because syphilis cross reacts with Lyme blots at 41 Kda due to their both possessing a key flagellar protein structure.

In 1994 Steere testified at a board of medicine hearing against Dr. Joseph Natole of Saginaw, Michigan, who was treating patients for chronic Lyme disease. Natole had many people on intravenous antibiotics, and authorities then charged him with medical malpractice and insurance fraud. Natole was ultimately stripped of his medical license for six months. In 2000 doctors in New York State who treated Lyme disease with long term antibiotic protocols were investigated by the NY Office of Professional Medical Conduct based on Dr Steere's outlines of treatment protocol as stated in his writings for the Infectious Diseases Society of America (IDSA)[16] and the American Lyme Disease Foundation (ALDF). None had their medical licences suspended.

These decisions came to personally haunt Steere and he was derided as the face of an uncaring group of doctors deemed to have political or private interests in their arguments against the possibility of chronic Lyme disease and subsequent long term antibiotic protocols. As the foremost researcher on Lyme, many doctors and insurance companies had followed Steere's lead on denying the possibility of chronic Lyme disease, and in turn, hordes of patients had started to stalk him.[17]

At first Steere tried to explain on scientific grounds why he didn't believe most patients who thought they had Lyme disease did in fact have it and, even if they did, why long-term antibiotics would not help. However, patients who believed they had the illness demonized him on the internet. Patients who had developed advanced Lyme encephalopathy and had spent years attempting to get proper diagnosis before finally finding a doctor to listen to them and run the proper testing also demonized him. Steere later had to hire security guards for his public appearances.

Steere's conservative view point on Lyme Disease and treatment for the illness came to be called the "Steere Camp" by patients and doctors who supported the theory of persistent infection and long term antibiotic treatments. Today the controversy still exists as researchers continue to study Lyme Disease in search of answers of the pathogenesis of the disease and proper treatment protocols.

Lyme vaccine

As chief of the rheumatology and immunology department at Tufts School of Medicine, Steere led the research effort on Lymerix, the preventive Lyme vaccine by SmithKline Beecham, now GlaxoSmithKline (GSK), which first appeared on the market in January 1999. The research took four years, spanned ten states, and involved 11,000 patients and 31 scientists.[18]

Lymerix works on the outer surface protein A (Osp-A) of Borrelia burgdorferi, the causative agent of Lyme Disease. Osp-A causes creation of antibodies from the body's immune system to attack that protein. Tests preceding the vaccine were done primarily on Lyme arthritis, and patients with neurological or cardiac manifestations were excluded.[19] [20][21]

The vaccine was shown to be 76 percent effective. The drug was taken in three shots administered over the course of a year. Some uncertainty remained about the vaccine's ultimate safety before it was released to the public, especially for people with certain conditions. When the National Vaccine Advisory Committee of the Food and Drug Administration (FDA) certified the drug in December 1998, members appended a list of concerns about the long-term effect of the vaccine. The FDA released the vaccine on public health grounds, recommending that it be considered by people at the highest risk. GSK took the drug off the market in 2002, citing poor sales, the need for frequent boosters, the high price of the vaccine, and the need to exclude children.

Current work

In his current work Steere is testing the hypothesis that synovial inflammation may persist in genetically susceptible individuals with antibiotic-resistant Lyme arthritis because of infection-induced autoimmunity via a pro-inflammatory mechanism within the joint. This outcome has been associated with an immunodominant T cell epitope of outer-surface protein A (OspA) of the spirochete.[22][23][24]

References

  1. ^ http://www.cdcfoundation.org/frontline/2001/new_york_gala_honors_epidemic_intelligence_service.aspx
  2. ^ Steere AC, Malawista SE, Snydman DR, Shope RE, Andiman WA, Ross MR, Steele FM. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three Connecticut communities. Arthritis Rheum. 1977 Jan-Feb;20(1):7-17. PMID 836338
  3. ^ Steere AC, Malawista SE, Hardin JA, Ruddy S, Askenase W, Andiman WA. Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum. Ann Intern Med. 1977 Jun;86(6):685-98. PMID 869348
  4. ^ Sternbach G, Dibble C (1996). "Willy Burgdorfer: Lyme disease.". J Emerg Med 14 (5): 631-4. PMID 8933327.
  5. ^ Steere AC, Hardin JA, Malawista SE. Lyme arthritis: a new clinical entity. Hosp Pract. 1978 Apr;13(4):143-58. PMID 658948
  6. ^ Steere AC, Malawista SE. Cases of Lyme disease in the United States: locations correlated with distribution of Ixodes dammini. Ann Intern Med. 1979 Nov;91(5):730-3.PMID 496106
  7. ^ Steere AC, Malawista SE, Newman JH, Spieler PN, Bartenhagen NH. Antibiotic therapy in Lyme disease. Ann Intern Med. 1980 Jul;93(1):1-8. PMID 6967272
  8. ^ Steere AC, Hutchinson GJ, Rahn DW, Sigal LH, Craft JE, DeSanna ET, et al. Treatment of the early manifestations of Lyme disease Ann Intern Med. 1983;99:22-6. PMID 6407378
  9. ^ BioInfoBank Libarary Retrieved May 28, 2007.
  10. ^ Steere AC, Malawista SE, Hardin JA, Ruddy S, Askenase W, Andiman WA. Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum. Ann Intern Med. 1977 Jun;86(6):685-98.PMID 869348
  11. ^ Steere AC, Gibofsky A, Patarroyo ME, Winchester RJ, Hardin JA, Malawista SE. Chronic Lyme arthritis. Clinical and immunogenetic differentiation from rheumatoid arthritis. Ann Intern Med. 1979 Jun;90(6):896-901. PMID 312615
  12. ^ France, David New York Times "SCIENTIST AT WORK: ALLEN C. STEERE; Lyme Expert Developed Big Picture Of Tiny Tick" May 4, 1999
  13. ^ Steere AC, Taylor E, McHugh GL, Logigian EL. The overdiagnosis of Lyme disease. JAMA. 1993 Apr 14;269(14):1812-6. PMID 8459513
  14. ^ Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med. 1990 Nov 22;323(21):1438-44. PMID 2172819
  15. ^ Lightfoot RW Jr, Luft BJ, Rahn DW, Steere AC, Sigal LH, Zoschke DC, Gardner P, Britton MC, Kaufman RL. Empiric parenteral antibiotic treatment of patients with fibromyalgia and fatigue and a positive serologic result for Lyme disease. A cost-effectiveness analysis. Ann Intern Med. 1993 Sep 15;119(6):503-9. PMID 8357117
  16. ^ Gary P. Wormser, Robert B. Nadelman, Raymond J. Dattwyler, David T. Dennis, Eugene D. Shapiro, Allen C. Steere, Thomas J. Rush, Daniel W. Rahn, Patricia K. Coyle, David H. Persing, Durland Fish, and Benjamin J. Luft GUIDELINES FROM THE INFECTIOUS DISEASES SOCIETY OF AMERICA: Practice Guidelines for the Treatment of Lyme Disease Clinical Infectious Diseases 2000;31:1-14 © 2000 by the Infectious Diseases Society of America
  17. ^ Grann, David New York Times "Stalking Dr. Steere Over Lyme Disease" June 17, 2001
  18. ^ Steere AC, Sikand VK, Meurice F, Parenti DL, Fikrig E, Schoen RT, Nowakowski J, Schmid CH, Laukamp S, Buscarino C, Krause DS. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group. N Engl J Med. 1998 Jul 23;339(4):209-15. PMID 9673298
  19. ^ Kalish RA, Leong JM, Steere AC. Association of treatment-resistant chronic Lyme arthritis with HLA-DR4 and antibody reactivity to OspA and OspB of Borrelia burgdorferi. Infect Immun. 1993 Jul;61(7):2774-9.PMID 7685738
  20. ^ Kalish RA, Leong JM, Steere AC. Early and late antibody responses to full-length and truncated constructs of outer surface protein A of Borrelia burgdorferi in Lyme disease. Infect Immun. 1995 Jun;63(6):2228-35.PMID 7768602
  21. ^ Kamradt T, Lengl-Janssen B, Strauss AF, Bansal G, Steere AC. "Dominant recognition of a Borrelia burgdorferi outer surface protein A peptide by T helper cells in patients with treatment-resistant Lyme arthritis". Infect Immun. 1996 Apr;64(4):1284-9.PMID 8606091
  22. ^ Ghosh S, Steere AC, Stollar BD, Huber BT. In situ diversification of the antibody repertoire in chronic Lyme arthritis synovium. J Immunol. 2005 Mar 1;174(5):2860-9. PMID 15728496
  23. ^ Steere AC, Klitz W, Drouin EE, Falk BA, Kwok WW, Nepom GT, Baxter-Lowe LA. Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide. J Exp Med. 2006 Apr 17;203(4):961-71. Epub 2006 Apr 3. PMID 16585267
  24. ^ Shin JJ, Glickstein LJ, Steere AC. High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic-refractory Lyme arthritis. Arthritis Rheum. 2007 Apr;56(4):1325-35. PMID 17393419

Further reading

  • Barbour, Alan Lyme Disease: The Cause, the Cure, the Controversy The Johns Hopkins University Press (April 1, 1996) ISBN 0-80-185245-5
  • Murray, Polly The Widening Circle: A Lyme Disease Pioneer Tells Her Story St. Martin's Press, 1st ed edition (April 15, 1996) ISBN 0-31-214068-1
  • Goldhagen, Harry, Rawlings, Julie 14th International Scientific Conference on Lyme Disease & Other Tick-Borne Disorders "Lyme Disease Controversies" June 6, 2001 Medscape Today
  • Grann, David New York Times Magazine "Stalking Dr. Steere Over Lyme Disease" June 17, 2001
  • Edlow, Johnathon A Bull's Eye: Unraveling the Medical Mystery of Lyme Disease Yale University Press; 2 edition (April 10, 2004) ISBN 0-30-010370-0

See also

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Allen_Steere". A list of authors is available in Wikipedia.
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