0 Article: The Mouse Trap: How One Rodent Rules The Lab

Slate recently posted a three part series on the use of mice in biomedical research and how that use has helped as well as hindered drug development and scientific understanding of human illness.

This three part series kicks off with "The Mouse Trap: the dangers of using one lab animal to study every disease", which examines the rise in the use of the murine (mouse) model  to test new pharmaceuticals and get a better understanding of human processes in illness. We also learn that this model - useful as it has been - has its drawbacks.

 Mark Mattson, neuroscientist, finds that murine studies may not accurately represent what happens between the study and control group when the control group is often overfed, sedentary, and develops cancer, renal problems, and diabetes - unlike a wild mouse living in its normal habitat. It was later discovered that medication which worked in chubby rodents did not go on to work in rodents with a normal weight and activity level.

Furthermore, in clinical trials on humans later on, the difference between plump mice and a diverse group of humans was too great. A drug which worked in the rodents did not work in humans at all.

Cheap, efficient, and mass produced, these mice are raised in germ-free barrier rooms and sometimes pumped with antibiotics. The ease in which they can be raised, bred, and genetically modified to single out specific processes similar to those in the human body to study has made mice very popular for researchers. While they can closely model many processes in the human body, are they a close enough match for modeling and testing everything?

Mattson argues they are not, and that science needs to wake up and take a closer look at how heavily mice have been used to make decisions that affect human medicine. He's not the only one, either - Clif Barry, the nation's leading expert on tuberculosis, thinks the murine model has shortcomings too. This is no clearer than in work in his own field: The latent form of TB that humans get is not one which can be found in mice. Mice do not experience a latent stage of TB - they only get progressively weaker, age, and die.

This particular passage from the article gave me a moment to pause and reflect:

"[...] for some patients a latent case of tuberculosis can suddenly become active. The granulomas rupture and propagate, spilling thousands of organisms into the lungs, where they can be aerosolized, coughed up, and passed on to a new host. Left untreated, the infection migrates into the bloodstream and other organs; widespread inflammation leads to burst arteries or a ruptured esophagus; and in about half of all cases, the patient dies.

The layered granuloma is the defining feature of human tuberculosis: The place where the host fights the infection (successfully or not), and the necessary site of action for any drug. To cure the disease, a treatment must be able to penetrate each ball of cells, whatever its type or composition; every last bacterium must be destroyed. "It's the structure of those granulomas that makes it so difficult to treat TB," says Barry. And they simply don't exist in mice.

If you infect a mouse with TB—if you spritz a puff of infected air into its nostrils through a trumpet, as so many labs do around the world—the animal's lungs quickly fill up with bacteria and immune cells, like a nasty case of pneumonia. There are no discrete balls of tissue, no well-defined granulomas sheathed in fibrin, no array of structures that harbor the bugs at various stages of development. The mice have no special, latent form of TB, either, and no way to pass on the disease. They simply die, after a year or two, of a slow and progressive decline.

That's why we've made so little progress using mice to generate new drugs and treatments, Barry tells me."

The article continues to outline the history behind why mice have become the dominant research model to use to determine whether or not a drug or treatment plan will be tried in clinical trials on people, and also discusses the setbacks generated by this decision. In the end, the verdict is that using mice has distinct limitations and a number of studies may be invalidated and useless because of it.

It does get me to wondering, of course, as to how useful the murine model is for studying Borrelia burgdorferi. Perhaps in some ways it is useful, but in others it is less so: Dr. Stephen Barthold has said mice are a poor model for neuroborreliosis.

And this does raise the question of which details are important in a study that the layperson will miss when reading it. The average person will read about the study design, and perhaps some discussion and the conclusion - but will one question the decision to use one research animal model over another? What about primers? What about media? What about any number of small details that once changed could result in a different outcome?

Read the full Slate article, and continue with the next two articles in the series. It is a fascinating look into the world of biomedical research, tradition, and profit.

Reference: http://www.slate.com/articles/health_and_science/the_mouse_trap/2011/11/lab_mice_are_they_limiting_our_understanding_of_human_disease_.html

This work by Camp Other is licensed under a Creative Commons
Attribution-NonCommercial-ShareAlike 3.0 Unported License.

Read More

1 Chalcolithic Iceman Had Lyme Disease Over 5,000 Years Ago

Ötzi, The Iceman, Cometh...

Thanks goes out to Joanne, from the Looking At Lyme Disease blog for posting about an article from National Geographic on the Iceman, a mummified man who had died over 5,000 years ago and has been a treasure trove of information for scientists ever since.

The original article is found here:

Iceman Autopsy - Unfrozen: There was only one way scientists could unlock the mystery of the famous Iceman. Take away his ice.


Source Link: http://ngm.nationalgeographic.com/2011/11/iceman-autopsy/hall-text

The entire article outlines the process of extracting and examining tissues and food from within the mummy - an interesting read in itself. But the part that will stand out for Lyme disease patients is this bit:

"Perhaps most surprising, researchers found the genetic footprint of bacteria known as Borrelia burgdorferi in his DNA—making the Iceman the earliest known human infected by the bug that causes Lyme disease."

It would be interesting to know exactly which Borrelia burgdorferi strain was found and in which tissue sample(s) it was found.

And reflecting on this, this indicates that Borrelia burgdorferi has been around for a long time and in Europe for a long time.

More Information On The Iceman:
http://en.wikipedia.org/wiki/%C3%96tzi_the_Iceman

This work by Camp Other is licensed under a Creative Commons
Attribution-NonCommercial-ShareAlike 3.0 Unported License.

Read More

4 The FDA Vault: Dr. Vijay Sikand On Lyme Disease & Lymerix

You know how I've said you can never guess what you're going to come across when you surf the net looking for other things?

Well, I came across this FDA transcript for a discussion on the Lymerix vaccine back in 1998. The original transcript contains an endorsement for the vaccine from the founder of Lyme Disease Foundation (LDF, not to be confused with the ADLF), who later determined the vaccine needed to be pulled from the shelves based on adverse reaction reports.

I'm setting aside any discussion of the Lymerix vaccine for now and just posting this statement from Dr. Vijay Sikand, an MD who practiced in Lyme, Connecticut... (items of interest are in bold)

UNITED STATES OF AMERICA 

DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
CENTER FOR BIOLOGICS EVALUATION AND RESEARCH
VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE MEETING
Tuesday, May 26, 1998 

  
The meeting took place in Versailles Rooms I and II, Holiday Inn, 8120 Wisconsin Avenue, Bethesda, Maryland at 9:00 a.m., Patricia L. Ferrieri, M.D., Chair, presiding.  


VIJAY SIKAND, M.D., Sponsor Rep
:

"...As I was just saying, I included research in Lyme disease as part of a primary care practice for a number of years. In early 1995, 1,200 volunteers came to my office to enroll in the SmithKline Beecham vaccine trial which we are discussing today. Almost three and a half years later now, greater than 92 percent of those patients are still providing me with clinical follow-up.
        
Why do we need a vaccine for Lyme disease? It has been almost a quarter century since Lyme disease was first described as an emerging infection in this country. During these years a number of factors, epidemiologic factors and clinical factors, have resulted in considerable morbidity in burgeoning numbers of patients.This burgeoning load of disease as well as the increasing number of patients thus set the stage for prevention of this disease with a vaccine.Today, I will present to you some of the factors in a brief synopsis illustrating the need for a vaccine for Lyme disease.The illustrations which I will present to you, some of them are from my private practice and some of them are from the vaccine study.

The first factor is an epidemiologic factor,and this has already been discussed by Dr. Schoen. And that is that there is indeed a progressive increase in incidence of Lyme disease. The second factor also epidemiologic is the relentless geographic spread of this disease. There are new endemic areas being created annually and the disease burden is indeed growing.
        
The ineffectiveness of preventive measures which we attempt to practice is another important factor. We have tried various chemical and other means. Why have preventive measures, which are indeed important, not been effective in preventing an increase in cases of Lyme disease?  And before I answer that question, let me underline the fact that I indeed believe it is important that we continue to practice preventive measures because of co-infection with other illnesses besides Lyme disease. 

One obvious reason is that it is very impractical to practice certain protective measures.  This individual in the Lyme, Connecticut area desires to do some outdoor work and does not want to be bitten by a tick. But the point is it is very difficult to ask children or anybody else for that matter to tuck pants into socks, et cetera, in the middle of July and August when the ticks are questing. We can certainly check our pets, but checking one's dog is indeed a Sisyphean task when the dog goes in and out of the house all day long. Probably the best protective measure, I think, in preventing Lyme disease is checking for ticks.  Unfortunately, kids will only allow you to do this up to a certain age. And of course one must be vigilant with oneself.

More specifically, I think one of the important reasons to consider when thinking about why protective measures are difficult to utilize and be effective in preventing this disease is simply the nature of the Ixodid tick bite itself. The bite of this tick when it is infected transmits not only saliva infected with Borrelia burgdorferi, but the saliva also contains certain anti-inflammatory substances which have an anesthetic effect.The end result of that is that tick bites in general are not noticed. In one study, over 80 percent of the patients who presented with definite Lyme disease did not remember a tick bite. It is therefore very hard to correlate the incidence of definite Lyme disease cases with preceding tick bites, and this is well known.

Furthermore, as has been eluded to earlier, the recurrence of disease in individuals is also well known. Unfortunately, in the majority of patients, the vast majority of patients, natural infection with Borrelia burgdorferi does not confer protective immunity. 

Difficulties in clinical diagnosis of this disease are also well known, and it is not my place today to give you an overview or detailed presentation of the clinical aspects of Lyme disease.However, a couple of issues that do spring up and which I would like to address are as follows. In particular, the specter of asymptomatic infection is something that troubles me a great deal and troubles a great number of my colleagues who need to treat Lyme disease. The obvious analogy with syphilis infection with Treponema pallidus is there to consider. It is well known that Borrelia burgdorferi indeed after asymptomatic infection can lurk or secrete itself in certain areas of the body, perhaps the central nervous system or perhaps the joint spaces, only to reappear months or maybe years later in the form of late stages of illness which are harder to diagnosis and treat.

In terms of the variability of Lyme disease, it is indeed a very variable infection, if not a very complex infection.  In its very simplest form, it is erythema migrans, well localized, which we can all recognize and which we can all easily treat and from which most patients can get better. However, erythema migrans is not a single beast. Certainly this is the one which we easily recognize and which I just referred to.Before I continue with further slides, let me point out that the erythema migrans lesions you are about to see are all biopsy lesions which were laboratory proven to be caused by Borrelia burgdorferi.

Sometimes erythema migrans can present as a pustular lesion as is this one in the popliteal fossa inviting the scalpel of a surgeon. Sometimes the lesions are vesicular in nature, inviting a diagnosis perhaps of herpes simplex infection.  Sometimes our round lesion is actually triangular. Sometimes it doesn't even look round or red at all and invites a diagnosis of an intertriginous fungal infection in the groin of this patient who was biopsied and proven to have Lyme disease. Sometimes the lesion is more plaque-like, inviting diagnosis of nummular eczema, psoriasis, or other similar lesions. Sometimes it is in unusual locations. Sometimes it is large like this one. Sometimes it is small with satellite areas. Sometimes it is multiple, appearing almost like urticaria or erythema multiform. Sometimes, as in this individual who was a placebo recipient in the Lyme 008 SmithKline Beecham trial, it presents with other manifestations of early dissemination. This individual came in mainly because he was concerned about his face and it felt kind of funny and it was weak on one side. When I asked him whether he had had any unusual rashes, he said oh do you mean this one, and he showed me his arm with that EM. This is simply to illustrate the infranuclar 7th nerve palsy with which he presented. This patient, by the way, had no history of a tick bite or any unusual antecedent illness which he could remember.

The next slide is the electrocardiographic tracing of a 37-year-old mom from Lyme, Connecticut, mother of three. Generally healthy and no medical problems. Early on the day that this electrocardiogram was taken, she went to her local health club and did her usual work-out, which went fine. However, when she came home that day, she noticed that she had some palpitations, a little shortness of breath, malaise, and things just didn't seem quite right, but she wasn't sure what. When her husband came home, she told him that maybe she had worked out a little bit too hard at the club. A few minutes later, he was reading the newspaper in an armchair and he heard a thump on the floor above. He ran up the stairs to find his wife unconscious briefly on the floor and called 911. On arrival at the emergency department, the patient presented with this tracing, which in retrospect was a superventricular tachycardia representing an escape rhythm. 

There was fortunately a very vigilant emergency physician who didn't understand quite why a 37-year-old healthy woman had completely passed out, and she had what was a relatively benign rhythm at that point. But he was wise and admitted her to the coronary care unit for further monitoring. Late that night and the early hours of the following morning, the CCU nurse noted that the patient had gone through progressive degrees of AV block culminating in complete atrial ventricular dissociation. A cardiologist was summoned. He inserted a temporary transvenous pacemaker. The patient was started on intravenous antibiotics for about a week in the hospital followed by a few more weeks as an outpatient.This patient also had no history of a tick bite.

Besides the difficulties in clinical diagnosis, we are all aware that quandaries in laboratory diagnosis are rife.We rely pretty much on serologic testing in the United States today to assist us in diagnosing Lyme disease. Unfortunately, serologic testing, as with other infectious diseases, provides only indirect evidence of infection. When we order a serologic test, it just tells us that the patient has been exposed to Borrelia burgdorferi and doesn't tell us whether the infection is active or whether it is a past infection. It is probably worth noting, since I have learned a lot, that we don't have the clinical luxury in private practice that we had in the SmithKline Beecham trial in which we had baseline sera on all the patients who enrolled so that when they presented with symptoms, we could draw acute and convalescent serologies so as to compare them with each other and with baseline to better understand what symptoms they are presenting with. But your average physician in the office just can't do this. A patient comes in with symptoms or signs of Lyme disease and you have to make a clinical diagnosis and it is not always easy and serology doesn't help. The fact that in particular the ELISA creates a great deal of false positive results is also problematic. 

In particular and commonly in infectious mononucleosis and other spirochetal disorders, even healthy people, juvenile rheumatoid arthritis and other autoimmune disease all can produce false positive results. Indeed, even with Western blotting recent reports have shown that infection with the agent of human granulocytic Ehrlichiosis can cause false positive Western immuno-blots.The false negatives that we deal with are generally caused by use of serology testing in patients who have early Lyme disease and in whom the serologic response with immunoglobulin M has not occurred to the extent to which it can be measured.

What do we have in the way of direct testing to try to see if the organism itself is actually there or evidence of it? Well, culture and PCR are what are out there right now.  However, these are unreliable and impractical. Culture and PCR are certainly not warranted for the diagnosis of erythema migrans. The polymerase chain reaction is indeed sensitive in joint fluid. However, the diagnosis of Lyme arthritis does not require PCR testing since serology is almost invariably positive at that stage. Clinical conditions such as complex neurological conditions when a test like sensitive PCR would be useful, unfortunately cannot be diagnosed that way because PCR and indeed culture are not sensitive for cerebrospinal fluid, nor are they sensitive for urine, blood, and other body tissues when later in the disease one might care to employ these techniques.

Finally, there are indeed many dilemmas in therapy. In particular, untreated or inadequately treated Lyme disease may lead to the chronic morbidity with which we are very familiar. Most commonly arthritis and the not common but complex neurological syndromes are what often result and which confront the primary care physician in the office diagnostically and therapeutically.These particular outcomes result in much more intensive, long-term expensive therapy, often in the form of long-term intravenous antibiotics. These are the patients who often are refractory to treatment. Indeed, these are the patients in whom symptoms seem to persist despite what we have given in terms of adequate antibiotic therapy by any known measure.

            In conclusion, we need a vaccine for Lyme disease because it is increasing in incidence and geographic spread.We need a vaccine for Lyme disease because there are problems in clinical diagnosis, its laboratory evaluation, and its treatment. We need a vaccine for Lyme disease because preventive measures are unfortunately ineffective. Lyme disease is indeed vaccine preventable. Availability of this vaccine would lead to a significant reduction in chronic sequelae and substantive morbidity.  Lyme vaccine is thus a critical new public health approach to the primary prevention of Lyme disease in the United States. Thank you very much."

Dr. Sikand and Dr. Steere were at the same meeting. It's obvious Sikand knew Lyme disease could lead to serious late stage Lyme disease and chronic persistent symptoms of infection. If it could be easily resolved with 2-3 weeks of antibiotics, would they have spent this much time, effort, and money on developing a vaccine and running clinical trials?

Everyone at this meeting - including Lyme disease patient advocates - wanted a vaccine. That it would lead to adverse events in some patients and be pulled from the market later was not what everyone thought at first - at first it was welcomed as a solution to preventing the worst of what Lyme disease could do to a person because it was hard to diagnose and treat.

1998. Thirteen years ago.

How much have things changed since then?

Why are we still looking at the same problems and issues?

Read More

5 One way to treat Borrelia naturally?

Many Lyme disease patients have used antibiotics for treating Lyme disease and other tickborne coinfections. They have years of scientific study behind them and many reports of patient improvement come from doctors and specialists - patients have had a lot of success with them.

But sometimes antibiotic use leads to various side effects, digestive problems, and potentially, undesirable secondary infection with C. difficile. Using probiotics can often help with digestive problems and prevent C. difficile, but it is not guaranteed.

In some cases - due to allergies or intolerance of the side effects - patients have to stop antibiotic treatment. Because of this, patients have opted at some point in their treatment to stop taking antibiotics after a while and switch to alternative treatments such as herbs.

Whether a patient decides to use antibiotics or herbs, one thing on the horizon seems certain: Eventually antibiotic resistance will lead to more restrictive use of antibiotics, and antibiotic resistance may challenge patients' ability to treat some of their own infections.

However, there is one completely natural possibility that might treat Borrelia and some other tickborne infections in the future which is rarely mentioned in the west other than as a curiosity - yet everyone in the world is surrounded by this abundant and prosperous source of healing from nature all the time.

Much as there are different probiotic bacteria are found in yogurt and probiotic supplements that Lyme disease patients take -- there are viruses in our environment that are helpful to us.

A lot people think of a few things when they hear the word "virus": they think of H1N1 or the swine flu, colds, herpes, HIV, and meningitis, for a start. Not good things. But like the probiotic bacteria that we consume in yogurt all the time, viruses are also present in our environment - in our food, our soil, our drinking water, and our own digestive systems.

Like adding probiotic mixes to your yogurt, these helper viruses have been approved by the FDA to be sprayed on the surface of cheese across the US in order to prevent the development of the bacteria, Listeria monocytogenes, from causing serious disease in pregnant women,  immunocompromised people such as cancer patients, and those with immuno-deficiences. Thousands of people can be severely sickened by Listeria and in some cases even die. So the use of these viruses in food such as cheese is beneficial.

In addition to providing protection from harmful bacteria in food, these helpful viruses have also been used to help save baby calves from dying of diseases which cause severe diarrhea and prevent salmonella from colonizing chickens.

The method for treating these cases was find out which bacterial strains the animals were infected with in order to find the viruses which would eat them. Then use these viruses just as they are found in nature, with no genetic engineering required - put the viral material in pills, injections, or lotions in order to treat the infection.

So this leads one to wonder if this all-natural, non-GMO treatment which is low-cost compared to antibiotics and so abundant in nature can kill off bacterial infections in animals - why can't they kill off infections in people too?

Well, they can.

Watch the next two videos, paying special attention to the first video.


The first video is a 48 minute BBC documentary on the use of viruses to kill bacteria, also known as "bacteriophage therapy" in the former Soviet republic of Georgia, in the Eliava Institute of Tblisi.

Note that if the institute seems run down, filming was done after the collapse of the Soviet Union and the hospital just came out of a civil war - thus buildings had poor maintenance, but the technology to use bacteriophage therapy was in place and used. (After a period of economic instability and social problems - followed by the Rose Revolution - Georgia and Tblisi have been doing much better in the past several years.)

So this documentary is a little dated but general principles remain the same - it explains very well what bacteriophage therapy is and how it has been used in Europe for over 60 years through the 1990's (it continues to be used today - more on recent research using phages will be posted this week).

Youtube (3 parts)

BBC Horizon - 1997 - The Virus That Cures

This second video is from Canadian television as well as CBS news and is more recent - it contains two clips back to back about two people who were treated with phage therapy and their results. Don't miss it - the results are amazing when you realize the initial prognosis each patient was given.

Case studies on phage treatment plus Evergreen College, 

Washington State phage research - [Time: 9:26 minutes]

Is bacteriophage therapy this effective? Does it have any pitfalls? Why don't we hear more about it here yet, given the rising number of cases of antibiotic resistance to deadly bacteria such as MRSA? What can it treat so far? How can this treatment help Lyme disease patients in the future? Here's just one more video just to get a different angle on it from Australian news (Channel 7 and Channel 9). It talks more about history, plus business investments and projections for human trials...

The Forgotten Cure - on Sunday Sunrise, Channel 7 - 

plus a short clip on phages from Channel 9

More on this later this week - for now, check out the videos and let me know what you think, including your own questions and concerns about this kind of medical treatment. [CO note: Continue reading part two of this series, "Phage Therapy and Borrelia burgdorferi".]

This work by Camp Other is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

Read More

27 What happened? The Early Days of Lyme Disease

This could end up being part of a series on the history of Lyme disease, but for now I wanted to share something from Polly Murray's book, The Widening Circle.

I really can't recommend this book enough for readers who are either Lyme patients or care about someone who is a patient - it is a well-written account of one woman's journey of struggling with strange symptoms that were plaguing her and her family for years. Her determination to find the cause, and how her actions led to the discovery of Borrelia burgdorferi in ticks led to all that people in the Lyme disease patient community are familiar with now.

Gandhi once said, "Be the change you wish to see in this world," and I think Ms. Murray's life reflects that statement.

Moving on to the question of "What happened?" in regards to how the introduction of Lyme disease back then led to the state of affairs over Lyme disease now (which is something people ask whenever they read the 1993 Senate testimony I recently posted): It's not that easily answered.

A combination of physicians who weren't sure how to treat Lyme disease not long after the disease had been discovered, physicians who came down ill themselves and self-treated for longer if their symptoms relapsed, the media's role in educating the public about Lyme disease leading to fearful patients, politicians in Connecticut who were slow to respond to patient demands for improvements in diagnosing and reporting the disease - all of these contributed to the atmosphere around Lyme disease.

The slow response of politicians and doctors to increasing numbers of patients suffering from Lyme disease led to the creation and growth of Lyme disease patient support groups. Even back then, by 1992 there were over 100 patient support groups for Lyme disease.

I quote an excerpt from Polly Murray's The Widening Circle, pages 266-267:

"Some doctors I have encountered think that Lyme disease is easily treated by a single course of antibiotics in its early stages; if patients fail to overcome the infection after one treatment, their future complaints are considered to be not associated with Lyme disease. These doctors believe that once a patient is treated, he or she no longer has Lyme disease.

In 1987-1988, tremendous media attention was given to the disease; I think this was generally beneficial. Correct information must prevail over ignorance. However, when the public saw the grave outcomes suffered by the patients who appeared on TV, many were scared that if they were bitten by a tick, they would have devastating illness. While a number of people do not respond to treatment or have not had treatment and have had severe complications, a proportionately far greater number are treated and seem to do well. (It is true, however, that some may relapse or enter another stage of the disease, sometimes many years later.)

Some doctors during this period of media attention were inundated by people worried that they might have the disease; they called this anxiety Lyme hysteria and Lyme paranoia. Some patients, as I have mentioned, were told they were "antibiotic junkies". There seemed to be many extremes in attitude, some physicians being unwilling to diagnose Lyme disease even with a classic presentation, and others willing to treat anyone with any vague symptom for Lyme disease. The unreliability of Lyme tests, as we shall see, did not help matters."

So, during this time, according to Polly Murray's account, people who were incredibly sick with Lyme disease were in the media spotlight and it led to fear in many people. The fear was not entirely unfounded - people do suffer greatly from Lyme disease. But if caught early, a significant number of patients go on to do well.

Why this is remains a complicated answer, and something that this blog investigates over time - it won't be limited to a paragraph or two of text.

At any rate, some people were afraid they had Lyme disease, and rather than be compassionate, some of these doctors were making negative statements about such patients. How many, I don't know - Ms. Murray doesn't elaborate on numbers.

It definitely does seem as if there was a greater mix of opinions in the medical profession about how to diagnose and treat Lyme disease. It was less monolithic, and the push from a handful of select professional medical organizations to set the standard of care for all primary care physicians wasn't in place yet.

Ms. Murray continued:

"A number of physicians continued to say that media hype was distorting the true profile of Lyme disease and was scaring people unnecessarily. True, the adverse outcomes were proportionately rare; however, to the rare patient with a devastating outcome, statistics are irrelevant. The fact remains that the more proper information citizens and physicians are armed with, the more likely they will be to protect themselves from Lyme infection and to detect and treat Lyme disease early so that devastating outcomes will be less likely.

As the number of cases continued to rise, some physicians in endemic areas began to see great numbers of patients with Lyme disease. With their growing experience, many of these physicians became convinced that suggested treatment regimens were insufficient to combat the disease in some cases and were calling for longer and more aggressive treatment. They began to encounter patients who clinically seemed to have Lyme yet tested negative, while a number of patients continued to have persistent symptoms and remained chronically ill for years despite treatment. This area of chronic complications is the most controversial and the most disheartening part of the Lyme disease story."

So as the number of cases went up, so did the number of patients who had seronegative Lyme disease and those who seemed to have a condition resistant to treatment.

To get a complete picture of how a disease is going to interact with a population, one can extrapolate what percentage will be infected from a smaller sample size - but it's harder when the presentation is not consistent across the board. Harder when a disease can be seronegative. Harder when it's suspected a disease can be asymptomatic and latent, only to present in its third, most serious stage later.

Part of what fueled the controversy back then was research in 1989 by V. Preac-Mursic and also doctors who were infected with Lyme disease who self-treated themselves longer than what Yale's suggested guidelines were at the time (that 2-4 week treatment length everyone in Lyme world is familiar with).

Ms. Murray wrote,

"Evidence has been found for the persistence of the spirochete in various parts of the body, despite antibiotic treatment and negative tests. A 1990 paper by V. Preac-Mursic and colleagues reported studies of patients who had originally been seropostiive, had been treated with antibiotics, and then had become seronegative. However, spirochetes could be cultured from skin specimens and spinal fluid from these patients, showing a persistence of the infection. In her summary, Dr. Preac-Mursic said, 'We conclude that early stage of the disease as well as chronic Lyme disease with persistence of B. burgdorferi after antibiotic therapy cannot be excluded when the serum is negative for antibodies against B. burgdorferi from CSF [cerebrospinal fluid] and skin biopsy in our patients after antibiotic therapy with normal CSF-values and negative serological tests for B. burgdorferi raises important considerations in the treatment of Lyme borreliosis.' Indeed, this study raises important questions as to both the adequacy of antibiotics in treating the disease and the reliability of the tests in detecting the disease."

The above mentioned study, for the curious, is this one:
PREAC-MURSIC V, WEBER K, PFISTER HW et al.: Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Infection (1989) 17:355-359.

To see the abstract for this paper (about halfway down the page) and papers with similar focus, I recommend this collection of links found at Lymenet Germany:
http://www.lymenet.de/literatur/niches.htm

There's a lot of science information on the Lymenet Germany web site - much of it in English - so I recommend checking it out some time.

Anyway, knowing this and other research about persistence only fueled the controversy at this time.

By the time 1992 rolled around, and the Fifth International Conference on Lyme Disease was held, the controversy was present at the conference itself.

As Murray reported:

"A number of papers submitted by physicians in endemic areas had been rejected by the conference's program committee. After protests from support groups and patients concerned that important new information on the disease was being excluded, the committee reversed its decision."

Does this sound familiar at all to any of you reading right now? Like maybe how things went down with the October 2010 Institute of Medicine workshop on tickborne illness?

She continued:

"It was my feelings that the patients who attended the conference primarily wanted better research and information on treatment evaluation and the development of more effective therapies and techniques of prevention. They were obviously interested in a cure. Many had found that the prescribed four-week treatment with antibiotics was not sufficient, and that they relapsed if not treated for long enough period of time. They questioned commonly accepted paradigms of the illness and believed that important questions were not being investigated."

And later on,

"After the conference a number of patient representatives wrote to its heads, citing six papers presented at the meeting which endorsed the theory that the spirochete persisted even after treatment and that a patient could be seronegative and yet have Lyme disease. They 'asked for more research on pathogenesis, long-term antibiotics and innovative drug delivery systems' and 'offered their services as participants in an NIH-sponsored effort to find a cure for chronic Lyme disease.'

Those patients sound just like me! That's what I'm asking for, too - more research on pathogenesis, long-term antibiotics, and innovative drug delivery systems.

Whoa.

So, as you can see, the issue of Lyme disease and its treatment being controversial has been with us for many years. The problems and concerns which patients faced twenty years ago are, sadly, the same problems and concerns they face today.

Where do we go next? What can patients do to change this state of affairs without reinventing the wheel?

A lot of awareness has been raised about Lyme disease in recent years - the publishing of Cure Unknown, the making and distribution of the film, Under Our Skin; the increasing online presence of large scale Lyme disease patient social networking sites, and numerous campaigns, fundraising drives, and events have been held to get more attention for Lyme disease.

How much this helps towards getting the research that is so badly needed remains to be seen. The funding and development of the Columbia University Lyme and Tickborne Diseases Research Center is definitely one of the bright spots in the Lyme patient community, but more such spots are needed and were needed years ago.

This work by Camp Other is licensed under a Creative Commons
Attribution-NonCommercial-ShareAlike 3.0 Unported License.

Read More

18 1993 Senate Testimony On Lyme Disease, Part 2

In Part 1, 1993 Senate testimony on Lyme disease given by Dr. Joe Burrascano was posted for review. In this part, various excerpts from Steere, other researchers, and others on the Senate committee will be reviewed with comments and questions.

As much as I know the Lyme patient community disdains Steere, and as much as I consider his March 2010 slideshow disrespectful of patients, there are a few places in this testimony where I found myself actually shaking my head in agreement with what he said back in 1993.

See what you think...

Alan Steere said:

"Research is certainly needed to improve laboratory tests
for Lyme disease, particularly for the development of tests
that detect the spirochete or its genes or antigens directly. 
However, improved laboratory tests will not by themselves
solve the problem of Lyme disease diagnosis. I believe that
clinical judgment will always be necessary."

I agree with him there.

Senator Dodd. Just let me get an answer to this,
and I'd be glad to. 

Do you think we ought to spend money on it?

Dr. Steere. Yes, absolutely. I think that Lyme disease is a great 
problem, and I think studies of it, particularly basic mechanisms 
of the disease, are of great importance. And I think that's what is 
most likely to help.

Again, I agree with this. Let's look at some more testimony and exchange with the senators...

Senator Metzenbaum. Thank you, Mr. Chairman. I have a cou- 
ple questions. 

Dr. Steere, I gather that the diagnosis of Lyme disease is not 
that fully developed that the physicians around the country really 
know enough about it or know enough about how to make the diag- 
nosis. Is that the thrust of what you are saying? 

Dr. Steere. I think that there are objective clinical criteria. I 
also think that it is possible to have laboratory tests that can help 
support that diagnosis. But nationwide, there is no standardization 
of that type of testing. 

There is certainly a great need for education, including education 
of physicians, about what this disease is and what it is like. And 
certainly, further research is needed to define that even more. 

Senator Metzenbaum. I remember when one of our fellow Mem- 
bers of Congress was diagnosed as having Lyme disease, Berkeley 
Bidell, a fine member of this body, and he resigned — or stepped out 
and didn't run for re-election; I guess he didn't actually resign — be- 
cause he thought he had Lyme disease, and subsequently found he 
did not. 

I get the feeling that across this broad United States, if you go 
to see Dr. Steere or one of these other gentlemen here, that you 
probably can get an accurate answer, but that there is a reasonable 
chance that if you go to many other doctors in the country — and 
this is not a broad-brush condemnation of them — but that it is not 
easily diagnosed and not easily diagnosed even after laboratory 
tests, unless the laboratories are particularly prepared for this kind 
of diagnosis. 

Now, am I misinterpreting what you are saying? 

Dr. Steere. No. I think that is absolutely true and very well-
stated.

Senator Metzenbaum. So therefore we have the problem of how 
we get the education out and how we get the diagnosis out. 

Now with respect to the treatment, you mentioned two particular 
products that can be used— I forget what they were; I'm sure you 
know what they are — with oral 

Dr. Steere. Oral therapy with doxycycline, a tetracycline type of 
antibiotic, and amoxicillin, a penicillin type of antibiotic. 

Senator Metzenbaum. And how effective is that? 

Dr. Steere. Well, I think for nonneurologic manifestations of the 
disease, they are quite effective. Neurologic manifestations of the 
disease are harder to treat, and how best to treat them is still 
being worked out.

Italics emphasis mine.

I think everything italicized is something that is important to note... The same problems Steere mentioned back in 1993 are the same problems the Lyme patient community is facing today.

I don't agree with Steere on everything, but I do think what he said back then is still true today.

Does anyone know how standardized today's testing is?

I think more studies of the basic mechanism of the disease would help a lot - quite possibly the most, too.

How much of our tax money has gone towards basic science research on pathogenesis and study of the spirochete versus other research? This is something a lot of people are asking, and not just me.

The other points Steere mentioned - that more first-line doctors such as primary care physicians need to be better educated to diagnose and treat early Lyme disease and that how best to treat neurological Lyme disease needs to be worked out - both of those are issues which I think still haven't been adequately addressed in the 18 years since he stated them.

There is other testimony there about serological testing and exchanges with Burrascano I'm not going to get into right now, some of which I disagree with Steere based on what research I've read thus far. These particular passages have been discussed in the Lyme patient community before, so I'm going to move on to other testimony by others...

Dr. BURRASCANO. The second point I wanted to address was the 
Simplification of the treatment ot Lyme disease Many patients who 
have been diagnosed after the disease has been present for more 
than just a short period of time, those who have had the illness for 
several months to several years before diagnosis, very often are not 
returned back to normal with antibiotic therapy as we know it 
today. 

One of the problems is that we don't know why people remain 
ill. We pretty much recognize that a lot of people will remain ill 
after Short courses of antibiotic therapy when they have late 
disseminated Lyme disease. The controversy which I tried to address 
today in my testimony is that we don't know why. 

There is an establishment of physicians university based who 
claim that the 30 days of treatment cures the patients; anything 
that is leftover has to be some arthritic phenomenon or some- 
thing they don't knew what it is and they send the patients off 
to a chronic fatigue clinic or to a fibromyalgia clinic. Yet there have 
now been many, many studies showing that these people still have 
the infection. 

So apparently, the infection can persist and evade the effects of 
antibiotics, and the presence of the organism somehow drives this 
reaction to keep the people sick. 

I have here an electron micrograph, a photograph of the spiro- 
chete, done by the NIH's lab at Rocky Mountain. This was taken 
from the urine of a patient who remained ill after one and a half 
years of antibiotics. This spirochete was identified positively as B. 
burgdorferi, the causative agent for Lyme disease. So in this one 
patient — and again, there are patients that you might see in the 
audience or who have testified today who are in a similar situa- 
tion — for them, the antibiotic therapy did not work. 

So what I am saying is that we need to focus our research on 
the real world of Lyme disease. No. 1, diagnosis is not simple or 
clear; the diagnostic test is not 100 percent. We need better testing. 
No. 2, treatment strategies as you might find in New England 
Journal articles are very basic minimums and do not cover the 
more chronic patients or those who are more seriously ill, and 
these chronic patients are not now being studied systematically for 
infection, and they should be."

Is evidence of a spirochete found in urine at the NIH's lab considered a significant finding? Why or why not?

Is evidence of Bb DNA found in a sample significant - why or why not?

In the discussion of findings from various research publications, it's been stated that finding bacterial DNA is not evidence of current infection. Finding a live, whole organism can be, though.

Here's some excerpts from Dr. Joe McDade... introduction included so you know who he is:

STATEMENTS OF DR. JOSEPH McDADE, ASSOCIATE DIRECTOR 
OF LABORATORY SCIENCE, NATIONAL CENTER FOR INFEC- 
TIOUS DISEASES, CENTERS FOR DISEASE CONTROL AND 
PREVENTION, ATLANTA, GA; AND JOHN R. LAMONTAGNE, DI- 
RECTOR, DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES, NATIONAL INSTITUTE OF ALLERGY AND INFEC- 
TIOUS DISEASES, NATIONAL INSTITUTES OF HEALTH, BE- 
THESDA,MD 

[...]

Dr. McDade. I certainly will do that. I think that the most im- 
portant problem that we have is a lack of recognition of Lyme dis- 
ease by the average physician. A recent CDC study in a north- 
eastern State showed that 82 percent of the cases of Lyme disease 
were reported by 7 percent of the physicians. 

Now, there are different ways of interpreting this data, but this 
was from a State in which Lyme disease is broadly endemic, and 
what that suggests is 

Senator Dodd. Which State are we talking about? 

Dr. McDade. Connecticut. 

Senator Dodd. I was afraid of that. [Laughter.] There are a lot 
of States in the Northeast, and so I was hoping 

Dr. McDade. It is not meant at all as an indictment of Connecti- 
cut. It probably reflects the situation nationwide, which is that ei- 
ther people are not reporting Lyme disease, or they aren't recogniz- 
ing it. And if they are not recognizing it, and they are not treating 
it early — and you have heard adequate testimony to this point — we 
have a serious problem. 

So to my mind, the physician awareness and education of the 
professionals is a key critical component, one that we have been 
working on and that needs a lot more attention. 

The second problem is one of diagnosis. This has been adequately 
documented and today, in testimony from a number of panelists, 
and clearly what it amounts to is a need for increased standardiza- 
tion and there is a need for increased research. CDC has been 
working in the last several months with the Association of State 
and Territorial Public Health Laboratory Directors to standardize 
some of the existing methodology, and that is currently under eval- 
uation. 

So, sounds like the same things that Burrascano and Steere said were a problem are problem in McDade's eyes, too.

To my readers in Connecticut: Do you have any research and evidence that reflects improvement in how many Connecticut doctors are accurately diagnosing and treating Lyme disease in the present and last few years?

I hope it has improved since 1993. That rate cited above - 7%? Sucks.

Dr. McDade. [...] But I think the point is that every- 
one recognizes that there are some deficiencies in the diagnostic 
criteria. The point is where do we go from here. I think there are 
in fact two different kinds of deficiencies. One is the lack of stand- 
ardization in evaluation of the existing methodologies. As I indi- 
cated, we have been working with the Association of State and Ter- 
ritorial Laboratory Directors to standardize what we have so that 
we can at least look uniformly across the States. 

Clearly, there are also many other things that are on the horizon 
that are being studied both by CDC intramurally, our extramural 
program, the NIH extramural program, which offer a lot of better 
alternatives. 

What wasn't perhaps said in some detail, without going into de- 
tails of the science, is that we are dealing with a very worthy ad- 
versary in B. burgdorferi. There are multiple strains of this orga- 
nism; it undergoes antigenic variation, and any diagnostic test that 
you have is going to be fraught with some difficulties. So this is not 
an easy problem, and everyone who is doing research on this recog- 
nizes these problems and is working toward them. But clearly, 
what we need to do is to employ our best efforts to try to find out 
which ones are there and which ones work in a real life situation. 

Here is where I wish McDade would have gone, actually - into details of the science behind B. burgdorferi. He is saying difference in strain and antigenic variation are an issue; that diagnostic tests are fraught with difficulties. I wish he would have gotten into more specifics here.

Senator Metzenbaum. Doctor, can I ask you, has CDC done any- 
thing about notifying the doctors of this country what to look for 
with respect to Lyme disease and what kind of testing is suggested 
in order to deal with it? 

I get the feeling that some doctors know about this, but there are 
a hell of a lot of doctors out there who don't know anything about 
it and just sort of push along. Am I wrong about that? Are you pro- 
viding information, or what is the fact? 

Dr. McDade. I think education is coming from a variety of 
sources, as was indicated earlier. For education of children, one of 
our cooperative agreements with the Lyme Disease Foundation — 
they have reached millions of people. Also, I can provide for the 
record if you like a list of the extramural funding; there are some 
half dozen various projects that are targeted directly or indirectly 
toward physician education. That is not to mention the general lit- 
erature, three or four articles published weekly by our Morbidity 
and Mortality Weekly Report, that address various issues, be they 
clinical, epidemiologic, prevention and control. 

There are a number of different approaches that are used. But 
as I'm sure you well can realize, any message that you might try 
to deliver, be it in the commercial sector, private sector, education- 
ally, or in medical, it is sometimes very difficult to reach 100 per- 
cent of the population, and it becomes more costly as you try to get 
100 percent awareness. 

Senator Metzenbaum. What I understand you to say is that doc- 
tors can find this information in a lot of places — in the journals and 
the medical literature — but that the Centers for Disease Control it- 
self has really — I think all of those hit a certain portion of the doc- 
tors of the country — but it seems to me that the CDC, without 
spending a fantastic amount of money, could do a much more effec- 
tive job of really getting to all the doctors in the country. 

Dr. McDade. We certainly don't at all think, Senator, that what 
we have done is enough, and we will continue to look at other ap- 
proaches and other venues in order to try to leverage resources to 
be able to reach the people maximally. I think that's about the 
most general way that I can State it. 

We are very aware not only of what we have done, but more 
aware of what we have not done. 

That sounds a lot like admitting that more could have been done when it wasn't, doesn't it?

Senator Metzenbaum. As I sit here, I get the feeling that this 
is a very challenging kind of illness or disease, but the fact is there 
is much more that can be done about it than we can do about a 
number of other illnesses, whether it is cancer or some other dis- 
ease of that kind. And what is bothering me is that I just have the 
feeling that there is a gap where the physicians in the field are 
really not up-to-speed as to diagnosis and treatment. And I think 
Dr. Steere pretty much confirmed that. And I think CDC is the 
agency to which we in Congress would look to ask, don't you have 
a greater responsibility than that which you are presently doing. 

Dr. McDade. I can say that your statement is entirely accurate, 
and CDC would love to have the opportunity to meet that chal- 
lenge.

Testimony immediately after this section goes on to discuss the recommendation that Dr. McDade request more funding from the gov't for the CDC to address this issue... Need to follow up to see exactly what happened after this, and where the funding was applied.

It seems to me that the exact same issues that concerned people in 1993 are still with us.

And now, onto Mr. LaMontagne's testimony...

[...]

Mr. LaMontagne. Lyme disease is now thought to be the most 
commonly reported arthropod-borne disease in the United States — it is 
certainly the most common tick-borne infection in the United States. 
The disease, caused by the spirochete B. burgdorferi, is transmitted 
primarily by ticks of the genus Ixodes. Lyme disease may be 
acute or self-limited or may develop into a chronic multisystem 
disease that can elicit a wide and unpredictable range of clinical 
manifestations. Current diagnostic tests, which are based on the 
detection of antibodies to B. burgdorferi, are useful, but far 
from perfect since individuals may vary widely in their immunological
response to infection, thus limiting the value of blood test 
results In the diagnostic process. 

As indicated, Lyme disease does not have a predictable clinical 
presentation or progression of symptoms. Most persons infected 
with B. burgdorferi respond to infection with strong immune 
responses, whereas others show no sign of infection in 
their blood. The organism also is very difficult and in some 
cases impossible to detect in infected individuals. Many published
descriptions indicate that the hallmark of Lyme disease is an
expanding red rash, known as erythema migrans, that may 
be accompanied by various other clinical signs and symptoms. 
Infected individuals actually present a highly variable array
of signs and symptoms, such as joint pain and nerve problems, 
that may be easily confused with those of other diseases. The 
ambiguities inherent in interpreting the results of blood tests 
for Lyme disease added to these nonspecific symptoms have led
to problems with both over- and under-diagnosis of the disease.

NIAID currently conducts and supports several projects
aimed at meeting the challenges of Lyme disease. Institute
goals for this area of research include: 

Improve our understanding of the immune response of infected 
individuals to B. burgdorferi. 

Improve our understanding of the biology and surface 
variation of B. burgdorferi. 

Develop tissue culture models of Lyme disease. 

Develop animal models of Lyme disease. 

Identify and characterize virulence factors and 
antigenic determinants of B. burgdorferi. 

Develop improved diagnostic and therapeutic strategies. 

Develop an effective human vaccine. 

Study the host range of B. burgdorferi in potential 
vector (transmitter) and reservoir (carrier) species. 

Study the biology and ecology of vector and 
reservoir species. 

Develop strategies for the control of Lyme disease 
transmission among reservoir species and to humans. 

I would like to take this opportunity to highlight for 
you recent advances made in our intramural and 
extramural programs and to briefly outline our research 
plans for the near future.

NIAID Intramural Research Program

INTRAMURAL RESEARCH ADVANCES 

Several NIAID scientists conduct Lyme disease research 
studies at the RML. Highlights of some of their recent 
efforts are summarized below. 

Scientists at RML have developed a highly sensitive 
and specific method to detect B. burgdorferi infection.
The assay works well with samples of urine, cerebrospinal fluid,
blood, and synovial fluid. Because the assay detects 
components of the infecting spirochetes rather than
immune responses to it, if it can be developed commercially,
the assay may prove useful for monitoring treatment
effectiveness as well.

A major stumbling block to developing diagnostic 
tests or a vaccine for Lyme disease is the elusive 
nature of the spirochete. The organism appears to evade the
immune system of the host by changing its surface proteins. 
NIAID scientists are studying changes in genes encoding 
two major outer membrane proteins of the spirochete. The 
studies may provide insights into the surface proteins of not only 
B.burgdorferi but also other borrelia organisms as well. 

NIAID'S researchers have genetically characterized samples
of Lyme disease bacteria taken from many patients in Europe, 
Asia, and North America. Based on genetic relatedness, the 
scientists have identified at least three distinct groups
of borreliae that can cause Lyme disease. The frequency
with which different Lyme disease symptoms occurs is 
known to vary in different geographic areas. The sci- 
entists have begun examining how the genetic distinctions 
within each group relate to clinical features of Lyme disease.

NIAID research recently showed that antibodies to 
a specific protein of the spirochete, p39, are produced 
only in response to an active B. burgdorferi infection 
and therefore can serve as reliable markers for Lyme disease. 
Using this observation, the researchers have developed 
three p39-based blood test kits that can help distinguish 
patients with Lyme disease from those with other disorders.

These kits have been approved by the Food and Drug Administration 
and are currently available to doctors, clinics, and 
hospitals nationwide. 

Scientists at the RML have demonstrated a characteristic of B. 
burgdorferi that may explain its ability to cluster in low 
numbers at the site of infection and yet cause a variety of 
reactions at other sites in the body. B. burgdorferi cells
release pouches or "blebs" from their surface that become distributed
widely throughout the body, unleashing a variety of immune system 
and tissue responses that may result in the diverse symptoms
seen in Lyme disease patients.

Coumermycin Al is an antibiotic that inhibits the enzyme
that catalyzes the coiling of DNA molecules and is required 
for bacterial replication and growth. Since the Lyme disease
spirochete has coiled molecules, NIAID investigators tested
the activity of this antibiotic on B. burgdorferi. They
found the Lyme disease spirochete to be 100 times more 
sensitive than other bacteria to this compound.

Although coumermycin Al or similar drugs are not ready
to be tested in humans, this research indicates that such
drugs should be investigated and developed further as 
potential therapies for human Lyme disease.

FUTURE PLANS 

The following future plans will be emphasized by NIAID
intramural scientists: 

Improve the sensitivity of the blood test kits and 
other available diagnostic tools. 

Continue studies of the variation and biological effect of 
Borrelial surface proteins with the goal of developing
an effective vaccine. 

Examine the attachment and penetration of spirochetes into
human cells as a possible mechanism of maintaining 
chronic infection. 

Examine the role of ticks in the maintenance and delivery
of the pathogen.

I realize that 18 years ago is a while ago, but what happened to some of this research?

Does anyone reading this know which assay they were talking about above, and if it was abandoned because of the previously stated idea that the presence of spirochetal DNA does not indicate the presence of current infection?

Is the evidence of a living spirochete the only indication of active infection? It seems there has been some argument in the literature between whether or not a small number of intact spirochetes can cause an infection and this hasn't been completely resolved. It definitely seems that serological testing isn't enough for some people.

From what is known today, there are more strains being found in different geographic locations than previously thought, with some vectors being birds - and also a greater number of disease-causing genotypes being found through Dr. Ben Lutz's studies... There's more work to be done there and it's ongoing.

How much research has the RML conducted on these pouches or bleb forms since then?

According to Tom Grier, "This bacteria replicates specific genes, and inserts them into its own cell wall, and then pinches off that part of its cell membrane, and sends the bleb into the host. Why it does this we don't know. But we do know that these blebs can irritate our immune system. Dr. Claude Garon of Rocky Mountain Laboratories has shown that there is a precise mechanism that regulates the ratio of the different types of blebs that are shed."

He also wrote, "In other bacteria the appearance of blebs often means the bacteria can share genetic information between themselves. We don't know if this is possible with Borrelia species. There have been reports of a granular form of Borrelia, which can grow to full size spirochetes, and reproduce. These granules are so small that they can be filtered and separated from live adult spirochetes by means of a micro-pore filter. (Stealth Pathogens, Lida Mattman Ph.D. 66)"

If these blebs are no longer considered significant, when did that change in opinion take place? Why don't we hear more about them today?

Why isn't Coumermycin Al being used to treat Lyme disease patients today, if Bb was considered 100 times more sensitive to this compound than any other bacteria?

Coumermycin is antibiotic derived from the bacteria, Streptomyces. Coumermycin, along with Novobiocin/Albamycin (Pharmacia And Upjohn), and Clorobiocin belong to a class of antibiotics known as aminocoumarins.

Years ago, Novobicin was removed from the market - this article from the 1970's indicates that 1 out of 5 people who used Panalba, an antibiotic made of Novobicin and Tetracycline combined, had allergic reactions to it and there were 12 fatalities recorded. So its use was discontinued.

Research on drugs that are aminocoumarins - and more specifically, DNA gyrase inhibitors - continues. So far, no treatment for patients with Lyme disease has come out of it.

In terms of that last bit - future plans of the NIAID scientists? I think they have done a lot of work on the second and fourth items, and some work on the first item, but really not much work on the third item at all.

I may be wrong, but that's my observation so far based on my own survey of the research done in, say, the past decade or so. I'd be glad to have someone point me towards more research on spirochetal attachment and penetration of human cells and chronic infection in general.

Those who are of a more conspiratorial bent may automatically point out that oversight of this item is deliberate. It may just be that with budgets not keeping pace with inflation and the fluctuating funds available, research teams decided to follow what was more profitable - vaccine and test kit development.

Or maybe researchers didn't even have a choice in what to research, and someone else decided where the funding was going for them - regardless of their own priorities and interests.

I understand the limits limited funding places on researchers - but I'd hope that if at some point one drops one of their goals, they can pick it up later.

What happened here? Why do so many physicians continue to miss diagnosis and treatment of early Lyme disease - is it lack of education, still, or is it that the clinical presentation is confounding so it's easy to miss even with education?

Have serological tests been standardized - and I don't mean in a Dearborn convention sense, which is its own separate and special issue - but for those tests which are outside of speciality labs, does there continue to be a wide range of result returns across the board?

What new antibiotic development has been undertaken? Funding has been present for more vaccine development, but requests for more new antibiotic development - even amid resistance concerns - were thwarted this past fiscal year.

There's a lot of questions I have to ask... if anyone else has followed the longer term arc of what I've mentioned above, please post your comments.

This work by Camp Other is licensed under a Creative Commons
Attribution-NonCommercial-ShareAlike 3.0 Unported License.

Read More

7 1993 Senate Testimony On Lyme Disease, Part 1

A lot of Lyme disease patients have referred to Dr. Joe Burrascano's Lyme disease treatment guidelines over the years, and from time to time,  some will mention how Dr. B testified before the Committee on Labor and Human Resources of the US Senate back at the 1993 hearing, Lyme Disease: A Diagnostic And Treatment Dilemma - Examining The Adequacy Of Current Diagnostic Measures And Research Activities In The Prevention and Treatment Of Lyme Disease. (Y 4.L 11/4: S. Hrg. 103-285)

Curious on that last bit, for years I tried to track down his testimony in vain and was unable to find it online. Then, more recently I found the entire document on the internet archive site, found here:

http://www.archive.org/stream/lymediseasediagn00unit/lymediseasediagn00unit_djvu.txt

I also have a printed copy of the actual hearing notes in my possession to check against the online version for accuracy in transcription.

Part of why I wanted it was because so many people had mentioned his testimony but no one had actually posted it anywhere it had been mentioned, and searches online when I first got ill with Lyme disease left me empty-handed.

Now the mystery is solved. The bulk of the testimony that everyone kept mentioning without citing it was this (very minor grammatical and typo edits made - refer to original text above for comparison):

Dr. Burrascano. Thank you very much for holding this commit- 
tee meeting, and again, thank you for the very nice introduction. 

You have heard today that there are many problems in the field 
of Lyme disease, and I want to address one of the core problems 
that you may not be aware of. Some have called this the "Lyme dis- 
ease conspiracy." 

There is in this country a core group of university-based Lyme 
disease researchers and physicians whose opinions carry a great 
deal of weight. Unfortunately, many of them act unscientifically 
and unethically. They adhere to outdated, self-serving views and at- 
tempt to personally iscredit those whose opinions differ from their 
own. They exert strong, ethically questionable influence on medical 
journals, which enables them to publish and promote articles that 
are badly flawed. They work with Government agencies to bias the 
agenda of consensus meetings and have worked to exclude from 
these meetings and scientific seminars those with ultimate opin- 
ions. 

They behave this way for reasons of personal or professional gain 
and are involved in obvious conflicts of interest. This group pro- 
motes the idea that Lyme is a simple, rare illness that is easy to 
avoid, difficult to acquire, simple to diagnose, and easily treated 
and cured with 30 days or less of antibiotics. 

The truth, however, is that Lyme is the fastest-growing infec- 
tious illness in this country after AIDS, with the cost to society 
measured in the billions of dollars. It can be acquired by anyone 
who goes outdoors, and very often goes undiagnosed for months, 
years, or even forever in some patients, and can render the patient 
chronically ill and even totally disabled despite what this core 
group of physicians refers to as "adequate" therapy. 

They feel that when the patient fails to respond to their treat- 
ment regimen, which is a common occurrence, it is not because the 
treatment has failed, but because they have developed a new ill- 
ness, what they call the "post Lyme syndrome." They claim that 
this is not an infectious problem, but a rheumatologic or arthritic 
malady due to activation of the immune system. 

The fact is, this cannot be related to any consistent abnormality, 
but it can be related to a persistent infection. As further proof, vac- 
cinated animals now in the vaccine trials whose immune system 
has been activated by Lyme disease have never developed this post 
Lyme syndrome. Yet on the other hand, there is a great deal of sci- 
entific proof that persistent infection can exist in these patients be- 
cause the one-month treatment did not eradicate the infection. 

Indeed, many chronically ill patients whom these physicians 
have dismissed have gone on to respond to, positively, and even re- 
cover, when additional antibiotics are given. 

It is also interesting to me that these individuals who promote 
this so-called "post Lyme syndrome" as a form of arthritis depend 
on funding from arthritis groups and agencies to earn their liveli- 
hood. Some of them are known to have received large consulting 
fees from insurance companies to advise the companies to curtail 
coverage for any additional therapy beyond the arbitrary 30-day 
course. And this is even though the insurance companies do not do 
this for other illnesses. 

Following the lead of this group of physicians, a few State health 
departments have now begun to investigate, in a very threatening 
way, physicians who have more liberal views on Lyme disease diag- 
nosis and treatment than they do. And indeed, I have to confess 
that today I feel that I am taking a personal risk, a large one, be- 
cause I am stating these views publicly, for fear that I may suffer 
some repercussions despite the fact that many hundreds of physi- 
cians and many thousands of patients all over the world agree with 
what I am saying here today. 

Because of this bias by this inner circle, Lyme disease unfortu- 
nately is both underdiagnosed and undertreated in this country to 
the great detriment of many of our citizens. Let me address these 
individually. 
 
With underdiagnosis, the first problem is underreporting. The 
current reporting criteria for Lyme disease are inadequate and 
miss an estimated 30 to 50 percent of patients. Some States cur- 
tailed their active surveillance programs and saw an artificial drop 
in reported cases of nearly 40 percent, leading the uninformed to 
believe incorrectly that the number of new cases of Lyme is on the 
decline. 

The reporting procedure is often so cumbersome that many phy- 
sicians have never bothered to report cases at all, and some physi- 
cians who have reported a large number of cases have found them- 
selves targets of State health department investigations. Finally, 
too many physicians and Government agents rely on the notori- 
ously unreliable serologic blood test to confirm the diagnosis. 

That brings me to my second point, which is the poor diagnostic 
testing. It is very well-known that the serologic blood test for Lyme 
is insensitive, inaccurate, not standardized, and misses up to 40 
percent of cases; yet many physicians, including many of those re- 
ferred to above, and the senior staff at CDC and NIH, insist that 
if the blood test is negative, then the patient could not possibly 
have Lyme. This view is not supported by the facts. Lyme is diag- 
nosed clinically and can exist even when the blood test is negative. 

The Rocky Mountain Lab of the NIH, which is the country s best 
laboratory for Lyme research, had developed an excellent diag- 
nostic test for this illness nearly 4 years ago, but further work on 
it has been stalled. Incredibly, if not for private donations to the 
Government from the National Lyme Disease Foundation, this and 
other related research would have had to be abandoned. Yet many 
physicians believe that thousands of dollars of grant moneys al- 
ready awarded by the Government to other outside researchers is 
poorly directed, supporting work of low relevance and low priority 
to those sick with Lyme. In spite of this, their funding continues, 
and the Rocky Mountain Lab is still underfunded. 

The third point is that the university and Government-based es- 
tablishment deny the existence of atypical presentations of Lyme, 
as some of those you have heard today, and the patients in this cat- 
egory are not being diagnosed or treated and have no place to go 
for proper care. 

The result of all this is that some Lyme patients have had to see. 
in my experience, as many as 42 different physicians over several 
years before being properly diagnosed, and also at tremendous cost 
to themselves. 

Unfortunately, the disease was left to progress during that time, 
and these patients were left forever ill, for by that time the illness 
was not able to be cured. 

Under the second category of undertreatment, number one is be- 
cause the diagnosis is not being made properly in many patients. 
Second, university-based and Government-endorsed treatment pro- 
tocols are empiric, insufficient, refer to studies involving inad- 
equate animal models, and are ignorant of basic pharmacology. 
They are not based on honest, systematic studies or on the results 
of newer information. 

Third, after short courses of treatment, patients with advanced 
disease rarely return to normal, yet many can be proven to still be 
infected and can often respond to further antibiotic therapy. Unfor- 
tunately, Lyme patients are being denied such therapy for political 
reasons and/or because insurance companies refuse to pay for these 
longer treatments. 

Fourth, long-term studies on patients who are undertreated or 
untreated demonstrated the occurrence of severe illness more than 
a decade later, reminiscent of the findings of the notorious 
Tuskegee Study. We have to take this illness seriously. 

Senator Wellstone. Dr. Burrascano, I don't want to be rude, but 
we're going to ask all of you to try to keep within about a 5-minute 
time frame. 

Dr. Burrascano. I am on the last paragraph. 

Senator Wellstone. OK I apologize. We just want to make sure 
that everybody has a chance to testify. 

Dr. Burrascano. I understand. 

Finally, the Lyme disease bacterium spreads to areas of the body 
that render this organism resistant to being killed by the immune 
system and by antibiotics, such as in the eye, deep within tendons, 
and within cells. The Lyme bacterium also has a very complex life 
cycle that renders is resistance to simple treatment strategies. 
Therefore, to be effective, antibiotics must be given in generous 
doses over a long period of time, sometimes many months, until 
signs of active infection have cleared. Also, because relapses have 
appeared very late, decades of follow-up are required before you 
can say someone has been adequately treated. 

I have to close by saying the very existence of hundreds of Lyme 
support groups in this country, and the tens of thousands of dissat- 
isfied, mistreated, and ill patients whom these groups represent, 
underscores the many problems that exist out in the real world of 
Lyme disease. I ask and plead with the committee to hear their 
voices, listen to their stories, and work in an honest and unbiased 
way to help and protect the many Americans whose health is at 
risk from what has now become a political disease. 

Thank you. 

----------

Comments:

It's 2011. This testimony was given in 1993. That's 18 years ago. 18. 

What has changed since this testimony was given?

I think most Lyme disease patients with persistent symptoms can relate to the statements made by Dr. Burrascano, and the echoes of what he said there have become part of the history and undercurrent for patients in discussions about insurance not covering their treatment and their ire about the IDSA Lyme disease treatment guidelines.

In discussion with a few people who were infected with Lyme disease many many years ago, I heard their uncommonly held opinion that this statement by Dr. Burrascano was perceived by them as a poor move on his part - even if some of the statements said were true. In doing so, he had raised the gauntlet and his open criticism before the Senate led to a backlash from different quarters.

As an aside, I'd really like someone to confirm if what I've heard about the time before his testimony was true: Prior to Burrascano's speech, some insurance companies were paying in full for IV antibiotic treatment for some patients. It wasn't a consistent practice - but in some places patients were able to get many months of IV antibiotic treatment covered by insurance. Insurance companies trusted the doctor's individual judgment for those cases.

Today, it is almost unheard of that an insurance company will cover any IV antibiotics for Lyme disease - if one receives 30 days' worth as a patient, they are lucky. It's almost as it neuroborreliosis doesn't happen, but it can and does happen earlier than one might suspect, given the stages of Lyme disease of which many people are familiar - and IV antibiotics is what neuroborreliosis requires.

Regarding the reaction to Burrascano's testimony, according to the LDF - there was retaliation - though I do not know the full story nor do I have independent confirmation of it.  What I do know is that to this day, there is a history of ongoing investigation into doctors who treat Lyme disease with long-term antibiotics - either by insurance companies, state medical boards, or both.

How this got started and who was the first doctor to do it is something I'd like to know - it had to be someone before Burrascano.

I look at all of this and what I hear in the Lyme patient community today springs forth from this event, and before this, the LDF, and before this, the Polly Murray story. I wonder how things came to be as they are - and inexplicably, why it is they haven't changed more in 18 years.

And interesting to note some of the other testimony by others that day... Sure, many people are familiar with the difference of opinion exchanged between Burrascano and Steere later that session, but how many are familiar with statements made by other researchers and doctors that day?

In my next post, part 2, I'll be pulling some of the more interesting passages out of the testimony for examination.

Note: For those of you who are concerned about my being plagued by virus yet still posting anyway when I said the frequency would slow down - I'm not great but okay. Most of what I'm writing here is copy and paste and not requiring much brain power... So I can post then lie down. - CO

This work by Camp Other is licensed under a Creative Commons
Attribution-NonCommercial-ShareAlike 3.0 Unported License.

Read More

3 Mullis' PCR and Borrelia burgdoferi's discovery

Remember I got a pile of books on loan to read? And remember that eccentric Nobel prize winner, Kary Mullis, who was featured in a TED video I posted?

According to Bull's Eye: Unraveling the Medical Mystery of Lyme Disease, Kary's new invention, developed in 1983 - Polymerase Chain Reaction (PCR) - was instrumental in learning more about Borrelia burgdorferi's history:

"One medical researcher who was quick to apply this technique in the medical arena was Dr. David Persing, then at the Yale University Department of Pathology. Being at Yale, Persing was interested in Lyme disease. Among many other projects, he and colleagues used PCR on 102 dried-out or alcohol-preserved tick specimens from the Museum in Comparative Zoology in Cambridge, Massachussetts. The ticks had been collected from various areas in New England between 1945 and 1951; each was tagged with the exact location where they had been collected. The researchers also examined another batch of ticks from the Smithsonian collection in Washington, D.C., some dating back as far as 1924. They found ticks that were positive for the DNA of B. burgdorferi from Montauk Point and from the adjacent Heather Hills State Park from the mid-1940s. 

Several years later, the same group with additional colleagues reported the results of similar experiments done on tiny biopsy specimens taken from the ears of archived mice from the same museum. They found two specimens that tested positive by PCR anaylsis for B. burgdorferi from mice orginally captured near Dennis, Massachusetts (on Cape Cod), in 1894! The DNA from these specimens was identical to the B31 strain that Willy Burgdorfer had found on Shelter Island. 

European investigators have reproduced these experiments using archived ticks from various parts of Europe including England and have found borrelial DNA dating back to the late 1880s as well. If the Lyme spirochete had been around for so long, why did it begin to surface as a recognized medical entity only in the past few decades? This question can be answered in one word --- deer."

I always find history fascinating, especially the connections between technology and information gathering. Here the PCR was invented around shortly after the time that news that Borrelia burgdorferi was the agent of Lyme disease was published in Science in 1982. We know far more about Bb now than we would have if this (or a similar technology) had not been developed at the time it was.

Read More