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.
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