LymeNet Newsletter Volume 1 Issue 27

Volume: 1
Issue: 27
Date: 17-Dec-93

Table of Contents:

ABSTRACT: (Neuroreport) Alzheimer's Disease -- a Spirochetosis? COMMENTARY: "Alzheimer's Disease -- a Spirochetosis?" By Carl Brenner ABSTRACT: (Proc Natl Acad Sci) Borrelia Burgdorferi is Clonal: Implications for Taxonomy and Vaccine Development NEW YORK TIMES: More Animals Are Said To Carry Lyme Disease OP-ED: Ivy League Ticks versus Redneck Ticks, By Karen Angotti

Newsletter:

***************************************************************************** * Lyme Disease Electronic Mail Network * * LymeNet Newsletter * ***************************************************************************** Volume 1 - Number 27 - 12/17/93

I. Introduction II. News from the Wires III. Op-Ed Section -- The Lighter Side IV. Jargon Index V. How to Subscribe, Contribute and Get Back Issues

I. ***** INTRODUCTION *****

Well, we made it. The Newsletter's first volume is now complete.

By all measures, our first year has been a huge success. In just 12 months, we established this publication and an international network of thousands of participants with a common goal: to find a solution to the Lyme disease epidemic.

In the process, we started building The National LymeNet, an even more ambitious project that will link physicians, researchers and support group leaders across the country via a computer network. In the next few months we will begin the final implementation phase of this project -- the testing period. We will provide you information on accessing the system as soon as it becomes available.

Effective January 1, 1994, the LymeNet FAX number will be: 908-789-0028. Please update your files to reflect this change.

Volume 2 of the LymeNet Newsletter is scheduled to begin publication in late January. Enjoy the Holiday season!

This issue of the Newsletter contains: * An amazing abstract on the correlation between Alzheimer's disease and LD * A commentary on this paper by Contributing Editor Carl Brenner * An abstract that questions the potential effectiveness of the ospA vaccines currently in development * Part of a New York Times article discussing the increase in animal reservoirs for Bb * A humorous commentary by author Karen Angotti

-Marc.

II. ***** NEWS FROM THE WIRES ******

TITLE: Alzheimer's disease -- a spirochetosis? AUTHORS: Miklossy J ORGANIZATION: Division of Neuropathology, University of Lausanne, Switzerland. REFERENCE: Neuroreport 1993 Jul; 4 (7): 841-8

ABSTRACT: The aetiology of Alzheimer's disease (AD), which affects a large proportion of the aged population is unknown and the treatment unresolved. The role of beta amyloid protein (beta A4), derived from a larger amyloid precursor protein (APP) in AD is the subject of intense research. Here I report observations that in 14 autopsy cases with histopathologically confirmed AD, spirochetes were found in blood and cerebrospinal fluid and, moreover, could be isolated from brain tissue. Thirteen age-matched control cases were without spirochetes. Reference strains of spirochetes and those isolated from brains of AD patients, showed positive immunoreaction with monoclonal antibody against the beta amyloid precursor protein. These observations suggest that spirochetes may be one of the causes of AD and that they may be the source of the beta amyloid deposited in the AD brain.

----

COMMENTARY By Carl Brenner LymeNet Newsletter Contributing Editor

This paper, if subsequently validated, would be one of the most significant -- and surprising -- publications in 20th century medicine. Judit Miklossy, a neuropathologist at the University of Lausanne, claims that she was able to isolate spirochetes from the tissues and fluids of 14 patients with Alzheimer's. Thirteen control cases were negative for spirochetes.

The cause of Alzheimer's disease has eluded researchers since the disorder was first described around the turn of the century. An association with beta amyloid protein is well documented, but the source of the amyloid protein deposits has never been discovered. In this study, Miklossy found both T. pallidum and B. burgdorferi, as well as the spirochetes she cultivated from the brain tissue of some Alzheimer's patients used in her study, showed positive immunoreaction using monoclonal antibody against amyloid precursor protein (APP). According to Miklossy, this suggests "that APP may be an integral part of the infectious agent and thus may be the source of the excess Beta-amyloid-4 deposited in the AD brain."

Miklossy successfully cultured spirochetes from the cerebral cortexes of three out of four AD cases and from the blood of four of five AD cases. In addition, she was able to observe spirochetes (via darkfield microscopy) in the blood and cerebrospinal fluid of all 14 AD cases. No spirochetes were observed, nor were any successful cultures obtained, from the control cases.

Apparently, no attempt was made by the author to identify the species of the spirochetes via protein sequencing, but the dimensions of the organisms (8 to 30 micrometers long and .2 to .3 micrometers wide) are morphologically suggestive of B. burgdorferi. (B. burgdorferi is the longest and narrowest of the borreliae, and borreliae in general are longer and more loosely coiled than either treponemae or leptospirae). Moreover, this would not be the first time that cases of AD and neuroborreliosis have been alleged to occur concurrently; two previous publications by Alan MacDonald exist on this subject. These papers, however, were greeted with considerable skepticism by a significant percentage of both the Lyme and Alzheimer's research communities. A subsequent study found no association between the two diseases [1]. Thus, Miklossy's findings reopen what had appeared to be a closed issue and represent a major departure from the current thrust of Alzheimer's research, which for the most part has rejected the idea of an
infectious etiology for the disorder.

It is difficult to discern which is more baffling: how the hundreds of researchers investigating Alzheimer's disease could have missed the connection to a spirochetosis if it in fact exists, or how Miklossy could have obtained such striking results if it doesn't. In a commentary published in the same issue of NeuroReport, three Alzheimer's researchers from the University of California at San Diego urge caution in evaluating Miklossy's findings and declare their "respectful skeptic[ism]." They point out, correctly, that electron micrographs and photomicrographs of what appear to be spirochetes can sometimes be misleading [2]. Still, even if the "spirochetes" in the photos turn out to be artifacts, it would not explain Miklossy's apparently successful attempts to culture the organisms from patient tissues. As the UCSD researchers point out, Miklossy's paper "will raise the interest, if not the voices and blood pressure, of many in the neuroscience community." The anomalous findings will no doubt stimulate
further research into a possible relationship between neuroborreliosis and Alzheimer's disease.

[1] Pappolla MA, Omar R, Saran B, et al. Concurrent neuroborreliosis and Alzheimer's disease: analysis of the evidence. Human Pathology 1989;20:753-7.

[2] For a discussion of this phenomenon, see Montenegro EN, Nicot WG, Smith JK. Treponema-like forms and Artifacts. Am J Opthalmol 1969;68:197-205.

=====*=====

TITLE: Borrelia burgdorferi is clonal: Implications for taxonomy and vaccine development AUTHORS: Dykhuizen DE, Polin DS, Dunn, JJ, Wilske B, Preac-Mursic V, Dattwyler RJ, Luft BJ REFERENCE: Proc Natl Acad Sci USA, 90:10163-10167, November 1993

ABSTRACT: The chromosomal genes fla and p93 and the ospA gene from a linear plasmid were sequenced from up to 15 isolates of Borrelia burgdorferi, which causes Lyme borreliosis in man. Comparison of the gene trees provides no evidence for genetic exchange between chromosomal genes, suggesting B. burgdorferi is strictly clonal. Comparison of the chromosomal gene trees with that of the plasmid-encoded ospA reveals that plasmid transfer between clones is rare. Evidence for intragenic recombination was found in only a single ospA allele. The analysis reveals three common clones and a number of rare clones that are so highly divergent that vaccines developed against one are unlikely to provide immunity to organisms from others. Consequently, an understanding of the geographic and genetic variability of B. burgdorferi will prove essential for the development of effective vaccines and programs for control. While the major clones may be regarded as different species, the clonal population structure, the geographic localization, and the widespread
incidence of Lyme disease suggests that B. burgdorferi should remain the name for the entire array of organisms.

=====*=====

HEADLINE: More Animals Are Said To Carry Lyme Disease SOURCE: The New York Times DATE: December 5, 1993, Sunday, Late Edition - Final SECTION: Section 13CN; Page 4; Column 5; Connecticut Weekly Desk BYLINE: By SAM LIBBY

STATE residents living near the coast and the mouth of the Connecticut River still face a greater risk of getting Lyme disease than residents of more northern or inland sections of Connecticut, health officials say.

But according to studies conducted by scientists at the Connecticut Agricultural Experiment Station in New Haven, the tick-borne disease is well established throughout the state, and there is no part of Connecticut where there isn't some threat of getting the disease.

"The disease is not only geographically spreading, it is also spreading through the state's ecology, the chief of the experiment stations entomology department, Dr. Louis A. Magnarelli, said. "There is evidence that more animals serve as reservoirs of infection for the disease. "

Studies based on tick collections and the presence of natural antibodies to the disease in the blood of deer show that Lyme disease is in all parts of the state, Dr. Magnarelli said. Increases in Litchfield County

The area of the state showing the greatest increase of infections is Litchfield County, where there were very few reported cases of the disease through the 1980's, he said.

Since the 1970's scientists have determined that white-footed mice are an important reservoir of infection of the disease. During the spring and summer the tiny deer ticks, which are infected with the Lyme organism, a spiral-shaped bacteria called Borrelia burgdorferi, feed extensively on the mice. During the winter the bacteria survives mainly in the blood of the infected hibernating mice.

When the juvenile deer ticks feed on the infected mice in spring and summer they become infected with the bacteria and spread the disease to all warm-blooded animals they feed on, including humans.

According to studies conducted by experiment station scientists in 1990 and 1991, local birds such as veeries, Carolina wrens, hooded warblers, and house wrens not only spread the disease to new areas, they also could serve as an important reservoir of infection, Dr. Magnarelli said.

Birds that feed on the ground are in turn fed upon by the deer ticks. The deer ticks will remain attached to the birds until they are engorged with the bird's blood and then they will drop off the bird hundreds, possibly thousands, of miles away. If the ticks are infected with the Lyme organism Borrelia burgdorferi it could introduce the disease to a completely new area, scientists said.

New studies indicate that the bacteria could persist in the blood of some bird species from June to mid-August. Uninfected ticks may become infected with the bacteria after feeding on infected birds.

The studies indicate that birds are not only an important agent for spreading the disease but could be an important part of the process in which the disease becomes established and persists in an area, Dr. Magnarelli said. ...

III. ***** OP-ED SECTION -- THE LIGHTER SIDE *****

Ivy League Ticks versus Redneck Ticks By Karen Angotti Author, "Lyme Disease: A Mother's Perspective"

When my husband went out to fetch the paper the other day, something happened that confirmed some suspicions we had been forming for several years now. He glanced at the paper for about ten minutes, then ran upstairs to take a shower. Lo and behold, as he pulled off his sock, he found an embedded tick happily suckling his blood from his calf. Now, we immediately knew this was no ordinary tick, for ordinary ticks do not bite people without wondering for 12 to 24 hours. How do I know this? All the research says so.

So, after much reflection and noticing other differences, we determined that here in Tennessee we do not have those Ivy League ticks they have up North. Ours must be the redneck variety without a fancy education. Our redneck ticks have not developed the gourmet appetites of the Ivy League varieties. And, therefore, do not spend all that time sequestering for the choicest cut. They also seem to be sorely lacking in table manners because they do not wash their hands, say their prayers, or unfold their napkin. These redneck ticks just say "Suppertime!" and chow down.

Another thing that managed to perplex us mightily was how we managed to attract hitchhiking ticks while never leaving the pavement. We would go to get the mail and come back in with the mail *and* and unwelcome visitor. Now, granted we do have to walk a third of a mile to get our mail, but, according to the papers we have read, ticks are not supposed to be able to exist in places that are hot and dry. And as anyone who has ever walked barefoot on black asphalt during the middle in the day in the summer down here will tell you, asphalt is not just hot, it is scalding.

So, not being scientists, but figuring we could surely solve thus mystery anyway, we grabbed some magnifying glasses and started sleuthing. Only to find the spellbinding spectacle of our hardier, more adventuresome redneck tick crawling out of a crack in the asphalt waving its greedy little arms for a few minutes then scuttling back down the crack to cool off. Those puny Ivy League ticks -- well, maybe vitamins will help.

Ticks that fell from the sky were even more puzzling. Our first thought was -- wings. But, no, anatomically they seemed to outward appearances look like the Ivy League ticks. However, we had already observed the amazing feats that these incredible mongrel redneck ticks could accomplish. So, positioning ourselves at the base of a tree with a magnifying glass firmly in tow, we readied ourselves to see, if despite what the books say, our ticks were climbing trees.

After several fruitless hours, we were packing up our gear and heading home when a frisky, grey squirrel darted up the tree. No -- could it be? Well, squirrels are furry little mammals and our ticks were no dummies. Why climb up a tree when you can *ride* in style. Our thinking expanded. We now noticed the birds fluttering around -- bluebirds, cardinals, robins, mockingbirds, jays, purple martins, sorrows, crows, ducks, geese, even egrets circled our house. Our redneck ticks did not need to grow wings! They just climbed on board for the ride of their life. The Ivy League ticks? They must not be made of the "right stuff."

And the moral of this little story is: If you believe everything the "experts" tell you, you *will* be bitten by ticks.

IV. ***** JARGON INDEX *****

Bb - Borrelia burgdorferi - The scientific name for the LD bacterium. CDC - Centers for Disease Control - Federal agency in charge of tracking diseases and programs to prevent them. CNS - Central Nervous System. ELISA - Enzyme-linked Immunosorbent Assays - Common antibody test EM - Erythema Migrans - The name of the "bull's eye" rash that appears in ~60% of the patients early in the infection. IFA - Indirect Fluorescent Antibody - Common antibody test. LD - Common abbreviation for Lyme Disease. NIH - National Institutes of Health - Federal agency that conducts medical research and issues grants to research interests. PCR - Polymerase Chain Reaction - A new test that detects the DNA sequence of the microbe in question. Currently being tested for use in detecting LD, TB, and AIDS. Spirochete - The LD bacterium. It's given this name due to it's spiral shape. Western Blot - A more precise antibody test.

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