UPTON, NY�A research team working at the U.S. Department of Energy's Brookhaven National Laboratory has determined the three-dimensional structure of a key protein on the bacterium that causes Lyme disease. Called OspC, the protein is derived from two strains of the Lyme disease bacterium. This research may lead to a second-generation vaccine that would be more effective than the current one.
The current vaccine is based on another Lyme disease protein, known as OspA, which was previously deciphered at Brookhaven. Both OspA and OspC are outer surface proteins of Borrelia burgdoferi, the bacterium that causes Lyme disease. Researchers from Brookhaven Lab, Stony Brook University's School of Medicine, the University of Rochester Medical Center and Rutgers University will report their findings on the structure of OspC in the March 1, 2001 edition of The EMBO Journal.
Spread by the bite of an infected deer tick, Lyme disease is the most common vector-borne disease in the U.S. Between 1982 and 1996, more than 99,000 cases were reported in the nation. Early symptoms of the disease include a bull's-eye rash and flu-like symptoms. If the disease is not promptly treated with antibiotics, more serious symptoms, including joint and neurological complications, may develop.
To determine the structure of OspC, the researchers used a technique at Brookhaven's National Synchrotron Light Source (NSLS) known as multiple wavelength anomalous diffraction. First, researchers grew crystals of the protein that could withstand the intense x-rays at the NSLS. To make large quantities of OspC, the team used the T7 gene-expression system, which was developed at Brookhaven.
Then the crystal was illuminated with beams of x-rays at different energies, and diffraction patterns were recorded on a detector. With the aid of powerful computers, the researchers then analyzed the diffraction patterns to gain the vital information needed to create an image of the protein structure.
John Dunn, a member of the research team from Brookhaven, explains that the structure of OspC is predominantly helical, and very different from OspA, which is flat. Also, a region on the surface of OspC has a strong negative charge. Dunn says the negatively charged region may be attracted to a positively charged site on the surface of human cells, helping the bacterium to cause infection. This feature is only found in the OspC protein derived from bacterial strains that cause human disease.
The scientists believe that a vaccine based on OspC will be more effective than the current OspA-based vaccine because the OspA protein is only present in the bacteria while they are in the cold-blooded deer tick's stomach, and not in the host. After the tick bites the warm-blooded mammalian host, the injected bacteria produce OspC in the host's bloodstream.
When the host is vaccinated solely with OspA, antibodies to this protein can only kill the bacterium inside the tick if it ingests these antibodies with its blood-meal. If the bacterium finds its way into the host, it changes into several other forms for which the vaccine offers no protection.
In contrast, an OspC-based vaccine would enable the host to make antibodies to kill the Lyme disease bacteria within the host's body.
Another member of the Brookhaven team, Subramanyam Swaminathan, added, "In order to develop an effective OspC-based vaccine, we'll have to know the three-dimensional structures of at least a few variants of OspC, especially those from invasive strains. Since we've solved the structure of OspC based on two infectious strains of the Lyme disease bacterium, we now have a prototype for determining the structure of OspC from other strains."
The U.S. Department of Energy's Brookhaven National Laboratory creates and operates major facilities available to university, industrial and government personnel for basic and applied research in the physical, biomedical and environmental sciences, and in selected energy technologies. The Laboratory is operated by Brookhaven Science Associates, a not-for-profit research management company, under contract with the U.S. Department of Energy.
"LOBBY DAY" IN ALBANY
Lyme Patients Advocate Reform Of The
New York Office Of Professional Medical Conduct
More than 200 Lyme disease patients from New York and several other states gathered in Albany, NY on Tuesday, March 27th and took their case to the offices of 36 lawmakers.
Organized by The Voices of Lyme and the Foundation for the Advancement of Innovative Medicine (FAIM), New York residents presented their case to ask for an investigation of the New York State Office of Professional Medical Conduct (OPMC) which is investigating the practices of several doctors who treat Lyme disease patients with long term illness.
With no single scientifically validated method for diagnosis or treatment, FAIM and Lyme patients nationwide question why any state health department would enforce select practice methods to the exclusion of other viable
options. They believe scientific debate should be settled in the scientific community but not by OPMC. Patients from states outside New York resent the chilling effect of New York's misguided police actions against doctors on whom their own physicians rely for effective treatment protocols. They are outraged that NY policy is limiting their care.
OPMC has brought charges of misconduct against Joseph Burrascano, MD and Richard Horowitz MD. Burrascano is the author of a protocol which sets forth guidelines for the treatment of Lyme disease in situations where the illness has not responded to short-term antibiotic therapy. Dr. Horowitz is a leading advocate of the theory that tick-born Borreliosis and Ehrlichiosis pose as serious a threat to New Yorkers as Lyme Disease.
At a press conference, speakers included Pat Smith, President of the Lyme Disease Association, a national research and support organization,; Dr. Howard Hindin, a board member of FAIM; and Dr. Steven Phillips.
STAMFORD [CT]- The red rash across Pedro's shoulder should have been a warning sign. So should have the rashes on his legs.
But it was the sudden fatigue, blurred vision and stiff muscles in his neck that forced the 33-year-old landscaper to see a doctor.
Pedro, a Guatemalan who has been a day laborer in the Stamford area for 11 years, did not wish to give his real name. He believes his illness is contagious and is afraid he will be stigmatized.
Pedro said he heard about Lyme disease from the contractor who hired him. He was even given a brochure about it, written in English. From what he understood, Lyme disease is transmitted from an infected deer tick.
Almost one year after he was diagnosed with Lyme disease, Pedro doesn't know much about it.
"I heard my boss tell me about it a long time ago, but I didn't pay attention," Pedro said in Spanish. "I didn't think it would affect me."
State and local health officials acknowledge there is little information about Lyme disease available in Spanish. But many of those who work in landscaping and construction - day laborers and migrant workers from Central and South America who move to the area for seasonal work - are at high risk.
"We've always said people who work and play outdoors need to take extra precautions," said Pat Mshar, epidemiologist for the state Department of Public Health. Information is available on the health department's Web site, but not in Spanish, Mshar said.
"If a population has been identified to show high rates of the infection, we will work with them to get the word out," she said.
Health officials at some clinics in Stamford and Norwalk acknowledge the disease is affecting men such as Pedro, who work six days a week, usually outdoors.
The men "are not too aware about it," said Julie Geiser, nurse practitioner for the Stamford Community Health Center on Henry Street.
"I tell them to tell their friends" about taking precautions such as daily tick checks, vaccinations and insect repellent, Geiser said.
But the vaccine is expensive, especially for the uninsured. "I believe publicity about it will get the word out," Geiser said.
In the past two years, Geiser has tested 12 men who described themselves as day laborers. Ten of them tested positive for Lyme disease.
Among those who didn't have the disease is 51-year-old Ramon Garcon, a gardener who said his wife found a tick in his head.
He said the bite forced him to go to the doctor, but he tested negative. He was urged to try the controversial vaccine.
"I knew nothing about Lyme disease," he said in Spanish. "I don't know anyone who has it."
Though Lyme disease is not contagious, infected ticks can jump from one person to another. Many day laborers live in small dwellings, several to a room. Infected ticks on one man's clothing can jump to another's. Some of the men have families, so women and children are at risk, health officials said.
Enriqueta Stavert of Wilton has started a crusade to bring information about the disease to the Hispanic community. She began translating pamphlets about Lyme disease into Spanish two years ago. She passes them out in churches, hardware stores, nurseries and to people she sees working outdoors in Wilton, Norwalk and Danbury. She also is trying to spread the word in Stamford.
Stavert said that when she approaches Spanish-speaking gardeners with her fliers, she gets mixed reactions, especially after she describes the symptoms - fatigue and fever and joint pain that can persist for weeks.
Signs may include rash - sometimes shaped like a bull's-eye - and flulike symptoms.
"They tell me, 'I've heard of something like this. My friend has it,' " Stavert said. "They all know someone who has Lyme disease. There are a lot of people getting it and they don't know what it is. Many don't want to go to the clinics to be tested because they are afraid they will be deported."
Many day laborers are in the country illegally.
The Centers for Disease Control and Prevention released new data last week that found the number of Lyme disease cases soared in the late 1990s.
The CDC recorded about 17,000 cases of Lyme in 1998 and more than 16,000 in 1999, mostly in the Northeast - especially in Connecticut - and the Midwest.
The United States averaged about 11,000 cases a year in the first eight years of the decade. Increased awareness of Lyme disease may account for some of the rise, according to the CDC.
But the agency attributed the jump mostly to cities sprawling into rural areas, new homes being built in wooded spots and a booming population of deer, which carry ticks that spread the disease.
"We know the risks of Lyme disease are higher among those who work outdoors," said Dr. Michael Parry, director of infectious diseases at Stamford Hospital.
Parry said he hasn't seen much information on the disease published in Spanish.
"I think they've heard about it, but they don't know exactly what it is," he said of the migrant workers.
The reason could be that Lyme disease hasn't been researched as well in minority communities, said Tom
Forschner, executive director of the Hartford-based Lyme Disease Foundation, which provides information worldwide.
"This has been a 'white' disease for the last few decades," Forschner said.
Red rashes such as those described by the CDC do not appear on all types of skin, Forschner said. There's a general assumption that minorities, who are more likely to live in urban settings, are not at risk for Lyme disease.
The foundation has received requests for Spanish-language pamphlets from California, but not from Connecticut, he said.
"We're readying our (Spanish) brochures now," Forschner said.
One of the problems has been figuring out the proper translation for "la enfermedad de Lyme," he said.
For Pedro, the Stamford landscaper who became ill last year, the struggle continues. He has taken the antibiotics and feels better, but each time he feels sick, he doesn't know whether it's the Lyme disease or a cold.
"This is a very ugly disease," Pedro said. "I had terrible headaches and I've fainted. I was in bed for nine days. For those of us who have to work each day, an illness like this means we lose money. Information in Spanish would be very good. I wouldn't wish this illness on anyone."
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Quote of the Month
"There are three stages to a new medical truth: |
COLUMBUS, Ohio 3/28/2001
A 90-million-year-old tick recently found in
the heart of New Jersey has left entomologists scratching their heads.
The tick is the oldest representative of the order Parasitiformes, increasing the order's age by 50 million years, said Hans Klompen, an assistant professor of entomology at Ohio State University.Tick experts currently believe that these insects evolved in South America.
Klompen describes the New Jersey tick, formally called Carios jerseyi, in the current issue of the journal Annals of the Entomological Society of America. He co-authored the paper with David Grimaldi of the American Museum of Natural History in New York City. In the mid-1990s, workers from the museum discovered the tick - along with several other species of plants and animals - in an 80-pound amber outcrop excavated from a vacant lot in central New Jersey. The museum asked Klompen to describe and categorize the tick.
Carios jerseyi did live at the same time as the dinosaurs, and Klompen admits that it's possible that the tick and its kin could have fed on the animals. "Ticks will feed on anything that has blood," he said.
Donation to Honor... Laura Sibert Cardoza - Ann and Ralph Sibert Dr. Joseph Burrascano - Dr. S. Chandra Swami - Linda DiFransico Dr. Michael Sowell, M.D. - Mrs. Sam Sowell |
"The Inside story of how a Family Practice doctor discovered the neurotoxin basis of chronic Lyme disease, sick building syndrome, chronic fatigue syndrome, Pfiesteria, ciguatera and other chronic illnesses. A newly discovered biomarker confirms the presence of the syndromes and helps to monitor beneficial effects of therapy."
This book is a remarkable collection of essays exploring the doctor's theories, his interactions with, and the ethics of, environmental and government agencies, as well as several thorough case studies all presented in an immensely readable form. Dr. Shoemaker incorporates his love of nature with his background as magna cum laude graduate of Duke University with a B.S. in molecular biology, minor in philosophy and his Duke Medical degree. He has given presentations and lectures at six conferences since October, 2000 and last summer was named Maryland Family Doctor of the Year.
Sir�Paolo Martinelli (Nov 18, p 1760)provides an excellent clinical and historical overview of Holmes-Adie syndrome (tonic pupil [one pupil reacts much more slowly to light or focusing than the other. Ed.] and areflexia [slowed or no tendon reflexes - particularly the ankle and knee-jerk reflexes.Ed] ) more commonly known in the USA as Adie syndrome. Although the syndrome has not been associated with "infection of conventional bacterial or viral origin", it is occasionally linked to early syphilis, parvovirus B19, and herpes simplex virus infections. We now report an association with neurological Lyme disease.
In a referral practice of about 140 patients with Lyme disease, we have seen three patients with predominant neurological symptoms who presented with Holmes-Adie syndrome (table). The diagnosis of Lyme disease was based on a history of tickbite, presence of an erythema migrans rash and positive serology for the spirochaete Borrelia burgdorferi. The duration of Lyme disease symptoms ranged from 2-16 years, and each patient developed a unilateral tonic pupil before the diagnosis of Lyme disease was made. All three patients had significant neuropsychiatric and cognitive defects, hyporeflexia, and facial dysaesthesia without anhydrosis. Rapid plasma reagin testing was negative in each case. Two patients had abnormal brain magnetic resonance imaging with white-matter lesions consistent with neurological Lyme disease. A decreased concentration of CD57 lymphocytes characteristic of chronic Lyme disease5 was found in two patients before antibiotic therapy. Of note, Holmes-Adie syndrome persisted in each case despite intravenous antibiotic therapy and partial resolution of other neurological symptoms of Lyme disease. [Table available on request. Ed.]
Neurological Lyme disease has been associated with various cranial nerve, meningeal, and neuropsychiatric abnormalities. Based on our clinical observation, it seems that Holmes-Adie syndrome might represent an early and unrecognised manifestation of Lyme disease. We suggest that patients presenting with this unusual neuro-ophthalmological syndrome should be tested for the Lyme disease spirochaete.
Raphael B Stricker, Edward E Winger,California Pacific Medical Center, San Francisco, CA 94120, USA; and Immunodiagnostic Laboratories, San Leandro, CA, USA
The Wilton [CT] Task Force raised over $210,000 (and still counting! ) for Lyme disease research at its second fund-raiser on March 3. A total of $375,000 has been raised by this group in just under one year. The overwhelming majority of the proceeds benefit Lyme Disease Research Programs, both current use and endowment accounts, established at Columbia University as part of a focused initiative last year. Columbia is helping coordinate research projects for researchers in and outside Columbia.
A highlight of "Dance the Lyme Away" was the announcement of the establishment of the Dr. Charles Ray Jones Endowed Student Fellowship, a $75,000 Columbia project that will name a medical student every year in perpetuity to study Lyme disease with community doctors. There will be an emphasis on pediatric Lyme. The fellowship will begin this summer. Dr. Jones was honored by several of his young patients during a very special presentation during the event.
This year's benefit had the support of an extraordinary honorary committee, including local celebrities and federal and state politicians and included: Michael Bolton, David Canary, Jose Feliciano, Charles Grodin, and Christopher Plummer. The committee also included Gov. John G. Rowland, Attorney General Richard Blumenthal, US Senator Christopher Dodd (CT), US Senator Joseph Lieberman (CT), US Senator Charles Schumer (NY) and several Connecticut State Legislators.
Dr. Fallon spoke of the need for research money and expressed gratitude for the Task Force's work.
Dr. Fallon told the audience, "Your efforts, either on the Dance floor or in the auctions, will have a nationwide impact on Lyme disease. The pilot funds -$5,000 or 10,000 or 25,000 - raised here tonight will allow researchers from around the country to try out new ideas that more established institutions like the NIH might not yet fund.....these pilot funds are key to the financing of novel, pioneering projects that will lead to the next breakthroughs in our battle against Lyme Disease. This is an extraordinary evening - a celebration of life - a celebration fueled by an explosion of support from people all over Connecticut. This is an evening wrought from the hard work of many folk - some quite ill - who persisted despite having little energy, diminished cognitive skills, and bodies crippled by pain. This evening was forged by the fire of love - love of one's children and of one's neighbors - and by a determination that the suffering and debilitation caused by Lyme Disease must stop."
Three hundred guests from Fairfield County and New York attended "Dance the Lyme Away".
The dance was chaired by Stephanie Torski and Molly Robertson of Wilton
(From "Lyme Matters" Newsletter Weekly Edition - March 28, 2001)
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