Allen Steere

Allen C. Steere is a professor of rheumatology at Harvard University and previously at Yale University. Steere is credited with discovering and naming Lyme disease, and he published almost 200 scholarly articles on Lyme disease between 1977 and 2007. [cite web | url=http://lib.bioinfo.pl/auth:Steere,AC | title=BioInfoBank Library - Steere AC | accessdate=2008-05-28] At a ceremony in Hartford, Connecticut in 1998, Governor John G. Rowland declared September 24 to be "Allen C. Steere Day."

Lyme disease research

In 1975, the Connecticut State Health Department received complaints from Polly Murray, a mother living in the small town of Lyme, Connecticut. Two of her children had been diagnosed with juvenile rheumatoid arthritis, but she knew of others in the area with similar symptoms.

A senior official with the Health Department contacted Allen Steere, who was studying rheumatology at Yale University. Steere had also gained practical experience with epidemiology during service with the Epidemic Intelligence Service, [cite web | url=http://www.cdcfoundation.org/frontline/2001/new_york_gala_honors_epidemic_intelligence_service.aspx | title=CDC Foundation - New York Gala Honors Epidemic Intelligence Service | accessdate=2008-06-26] a CDC program set up in the 1950s to track epidemics worldwide. [cite web | author=Centers of Disease Control | url=http://www.cdc.gov/eis/ | title=EIS homepage | accessdate=2008-06-26]

Steere met with Ms. Murray, who gave him a list of children who shared a set of symptoms. Steere called each affected family, representing 39 children in all, and he found an additional twelve adults suffering from what was thought to be juvenile rheumatoid arthritis. [cite journal |author=Steere AC, Malawista SE, Snydman DR, "et al" |title=Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities |journal=Arthritis Rheum. |volume=20 |issue=1 |pages=7–17 |year=1977 |pmid=836338 |doi=10.1002/art.1780200102]

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 vector rather than a flying one or a spider, but most patients did not remember being bitten.cite journal |author=Steere AC, Malawista SE, Hardin JA, Ruddy S, Askenase W, Andiman WA |title=Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum |journal=Ann. Intern. Med. |volume=86 |issue=6 |pages=685–98 |year=1977 |month=June |pmid=869348]

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.fact | date=June 2008

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.fact | date=June 2008

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.cite journal | author = Sternbach G, Dibble C | title = Willy Burgdorfer: Lyme disease. | journal = J Emerg Med | volume = 14 | issue = 5 | pages = 631–4 | year = 1996| pmid = 8933327 | doi = 10.1016/S0736-4679(96)00143-6] The syndrome first found in and around Lyme and Old Lyme, Connecticut came to be called "Lyme Arthritis" and later "Lyme Disease". [cite journal |author=Steere AC, Hardin JA, Malawista SE |title=Lyme arthritis: a new clinical entity |journal=Hosp Pract |volume=13 |issue=4 |pages=143–58 |year=1978 |month=April |pmid=658948 |doi= |url=] [cite journal |author=Steere AC, Malawista SE |title=Cases of Lyme disease in the United States: locations correlated with distribution of Ixodes dammini |journal=Ann. Intern. Med. |volume=91 |issue=5 |pages=730–3 |year=1979 |month=November |pmid=496106]

In 1980, Steere and colleagues began to test antibiotic regimens in adult patients with Lyme disease. [cite journal |author=Steere AC, Malawista SE, Newman JH, Spieler PN, Bartenhagen NH |title=Antibiotic therapy in Lyme disease |journal=Ann. Intern. Med. |volume=93 |issue=1 |pages=1–8 |year=1980 |month=July |pmid=6967272] [cite journal |author=Steere AC, Hutchinson GJ, Rahn DW, "et al" |title=Treatment of the early manifestations of Lyme disease |journal=Ann. Intern. Med. |volume=99 |issue=1 |pages=22–6 |year=1983 |month=July |pmid=6407378]

Steere first published about neurological and cardiac symptoms involved in his early studies of Lyme disease in 1977. Steere first published work about chronic manifestations of the disease in 1979. [cite journal |author=Steere AC, Gibofsky A, Patarroyo ME, Winchester RJ, Hardin JA, Malawista SE |title=Chronic Lyme arthritis. Clinical and immunogenetic differentiation from rheumatoid arthritis |journal=Ann. Intern. Med. |volume=90 |issue=6 |pages=896–901 |year=1979 |month=June |pmid=312615]

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.fact | date=June 2008

Lyme disease controversy

By the mid 1990's, Steere had watched Lyme disease gain acceptance, but he worried that Lyme disease had become a "junk-drawer diagnosis", covering maladies ranging from chronic fatigue syndrome (CFS), fibromyalgia to hypochondria. Steere was concerned that many people with no evidence of past or present Lyme disease were receiving antibiotic treatments, especially treatments beyond the recommended four week treatment guideline protocol, "were being done more harm than good".cite news |first=David |last=France |title=Scientist at work: Allen C. Steere; Lyme expert developed big picture of tiny tick |url=http://query.nytimes.com/gst/fullpage.html?sec=health&res=9C00EED8173CF937A35756C0A96F958260 |work=New York Times |date=1999-05-04 |accessdate=2008-06-26]

Writing in the "Journal of the American Medical Association" (JAMA) in 1993, Steere and colleagues stated that Lyme disease had become "overdiagnosed" and overtreated. [cite journal |author=Steere AC, Taylor E, McHugh GL, Logigian EL |title=The overdiagnosis of Lyme disease |journal=JAMA |volume=269 |issue=14 |pages=1812–6 |year=1993 |month=April |pmid=8459513 |doi= |url=] This statement became a rallying point for what advocacy groups call the Lyme disease controversy. In the face of mainstream medical opinion, some doctors and patient advocacy groups claim that Lyme disease can develop into a chronic disease requiring high doses of antibiotics over long periods of time.

Although the term "chronic Lyme" was once used by Steere and others to define persistent complications following acute Lyme disease, [cite journal |author=Logigian EL, Kaplan RF, Steere AC |title=Chronic neurologic manifestations of Lyme disease |journal=N. Engl. J. Med. |volume=323 |issue=21 |pages=1438–44 |year=1990 |month=November |pmid=2172819 |doi= |url=] various Lyme advocacy organizations and a dissident group of doctors called the International Lyme and Associated Diseases Society (ILADS) have redefined the term to describe a wide range of symptoms, mostly in patients who have no evidence of Lyme disease.cite journal | author = Feder HM, Johnson BJB, O'Connell S, et al. | title = A Critical Appraisal of "Chronic Lyme Disease" | journal = N Engl J Med | volume = 357 | issue = 14 | pages = 1422–30 | doi = 10.1056/NEJMra072023 | year = 2007] Steere and his colleagues averred that even patients with a positive serology for "Borrelia" infection and with symptoms resembling those of CFS or fibromyalgia, would not be helped by further antibiotics. [cite journal |author=Lightfoot RW, Luft BJ, Rahn DW, "et al" |title=Empiric parenteral antibiotic treatment of patients with fibromyalgia and fatigue and a positive serologic result for Lyme disease. A cost-effectiveness analysis |journal=Ann. Intern. Med. |volume=119 |issue=6 |pages=503–9 |year=1993 |month=September |pmid=8357117 |doi= |url=http://www.annals.org/cgi/content/full/119/6/503] Further research has supported this position entirely.fact | date=June 2008

Steere's prominence, and his support of the medical view that patients with "chronic Lyme disease" often have no actual evidence of Lyme disease and are not helped by long courses of antibiotics, led to him being targeted, harassed, and threatened with death by patients and advocacy groups angered by his refusal to validate their belief that they suffer from chronic Lyme disease. [cite news |first=David |last=Grann |title=Stalking Dr. Steere over Lyme disease |url=http://www.nytimes.com/2001/06/17/magazine/17LYMEDISEASE.htm |work=New York Times |date=2001-06-17 |accessdate=2008-06-26]

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. [cite journal |author=Steere AC, Sikand VK, Meurice F, "et al" |title=Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group |journal=N. Engl. J. Med. |volume=339 |issue=4 |pages=209–15 |year=1998 |month=July |pmid=9673298 |doi= |url=http://content.nejm.org/cgi/content/full/339/4/209]

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. [cite journal |author=Kalish RA, Leong JM, Steere AC |title=Association of treatment-resistant chronic Lyme arthritis with HLA-DR4 and antibody reactivity to OspA and OspB of Borrelia burgdorferi |journal=Infect. Immun. |volume=61 |issue=7 |pages=2774–9 |year=1993 |month=July |pmid=7685738 |pmc=280920 |doi= |url=http://iai.asm.org/cgi/reprint/61/7/2774 | format=PDF] [cite journal |author=Kalish RA, Leong JM, Steere AC |title=Early and late antibody responses to full-length and truncated constructs of outer surface protein A of Borrelia burgdorferi in Lyme disease |journal=Infect. Immun. |volume=63 |issue=6 |pages=2228–35 |year=1995 |month=June |pmid=7768602 |pmc=173290 |doi= |url=http://iai.asm.org/cgi/reprint/63/6/2228 | format=PDF] [cite journal |author=Kamradt T, Lengl-Janssen B, Strauss AF, Bansal G, Steere AC |title=Dominant recognition of a Borrelia burgdorferi outer surface protein A peptide by T helper cells in patients with treatment-resistant Lyme arthritis |journal=Infect. Immun. |volume=64 |issue=4 |pages=1284–9 |year=1996 |month=April |pmid=8606091 |pmc=173916 |doi= |url=http://iai.asm.org/cgi/reprint/64/4/1284 | format=PDF]

The vaccine was shown to be 78 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.fact | date=June 2008

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. [cite journal |author=Ghosh S, Steere AC, Stollar BD, Huber BT |title=In situ diversification of the antibody repertoire in chronic Lyme arthritis synovium |journal=J. Immunol. |volume=174 |issue=5 |pages=2860–9 |year=2005 |month=March |pmid=15728496 |doi= |url=http://www.jimmunol.org/cgi/content/full/174/5/2860] [cite journal |author=Steere AC, Klitz W, Drouin EE, "et al" |title=Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide |journal=J. Exp. Med. |volume=203 |issue=4 |pages=961–71 |year=2006 |month=April |pmid=16585267 |doi=10.1084/jem.20052471 |url=http://www.jem.org/cgi/content/full/203/4/961] [cite journal |author=Shin JJ, Glickstein LJ, Steere AC |title=High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic-refractory lyme arthritis |journal=Arthritis Rheum. |volume=56 |issue=4 |pages=1325–35 |year=2007 |month=April |pmid=17393419 |doi=10.1002/art.22441 |url=http://www3.interscience.wiley.com/cgi-bin/fulltext/114203642/HTMLSTART]

See also

*Lyme disease
*Lyme disease controversy
*Jorge Benach
*Willy Burgdorfer
*Spirochete

References

Further reading

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