http://www.iadvocatehealth.org/protozoa ... tion0.aspx
Protozoal Infection -- The Next Big Discovery?
A New Protozoa Appears Linked To Mystery Diseases
By Marc Braman, MD, MPH
New findings of a previously unknown protozoa in patients with conditions such as lupus, chronic fatigue, multiple sclerosis, Lou Gehrig's disease, etc may prove to be a major medical breakthrough. While there are still some pieces of the puzzle to be proven, there are many pieces that fit so far. Treatment may prove very challenging, but lifestyle and diet has a surprisingly profound effect on the organism and patients.
The following is Part I of the transcript of a recent interview with Steven Fry, MD. Some parts are somewhat technical. We have tried to provide brief definitions or explanations throughout.
Analysis and explanation will follow Part II.
Please do not expect your physician or other health care provider to know about what is covered here. You will not even find most of this information on Dr. Fry's lab's website. Understand that it will be some time before some of the remaining studies that test "causation" are completed and this information is more widely known and used.
Braman: What I’d like to do by way of outline is: If you can just share a little bit about how you came to get into this rather unique field, what you are currently doing, what you are finding from the testing that you are doing, and what you are seeing in terms of patient outcomes -- just kind of an overview. And then in part two I’d like to move into what you are seeing and finding relative to the lifestyle effect on these conditions and the lab findings that you are doing -- so kind of a part 1 and a part 2.
Fry: Okay. So, I first got into this area -- well, let me backtrack a little bit and give you my background. I have a bachelors degree in Microbiology, a masters degree in Molecular Biology, then I went to medical school, then I did a transition internship, then I did two years of surgical pathology, and ended up in general practice. And while I was in general practice, I got intrigued by those patients who were perfectly healthy, and then would go on a trip, or something would happen, and they would develop a flu-like illness, and they would develop what we now call chronic fatigue syndrome.
Then the real breakthrough was about seventeen or eighteen years ago when I had one of my patients who had fibromyalgia, which is very similar to chronic fatigue syndrome -- in many ways I feel like they are the same disease, or the same disease entity. She gave me a book written by Henry Scammell, I think the title was ‘Why Arthritis’, [probably actually “The Arthritis Breakthrough” by Henry Scammell with Thomas McPherson Brown, MD] it was on the best sellers list in the early 90’s. It talked about Thomas McPherson Brown, the rheumatologist, who was one of the chief rheumatologists at Washington University. He was using antibiotics -- primarily tetracyclines -- to treat autoimmune disease. So she brought me this book, and I was a little hesitant, but I read the book and I was really impressed by it, and I said, “What’s the harm here putting her on minocycline? I mean I put teenagers on minocycline for acne.” So you know, the risk benefit ratio was huge in that sense. And I started her on minocycline, and she got amazingly better on a course minocycline. Her fibro got better, her lupus got better, and so I started to pursue that, and with more and more patients I started to use tetracyclines for therapy.
And then finally I started -- you know, there was a network of physicians who worked with Dr. Brown’s former technique, and I got on, I guess, a group that was referring patients through that -- I was one of the few in the southwest doing it. And I started getting patients with lupus, and rheumatoid arthritis, and one thing led to another, and I would start doing patients with MS [multiple sclerosis].
And then about eleven years ago I was impressed by an article out of Italy on chronic fatigue syndrome, and I just borrowed money, bought a nice research grade microscope, and started developing some stains. And in about six months I developed a stain that was picking up bacteria attached to red blood cells. I thought it was bacteria at the time, turns out it was. And then we started to see ring shapes that looked very similar to malaria, but it really wasn’t malaria. Anyway, one thing led to another, and it turns out that what we were looking at was actually a variety of different bacteria attached to red blood cells. Now the old coin name would be bartonella, or hemobartonella, and it turns out on a molecular level it was a lot of different kinds of bacteria. And the intracellular bacteria, or intraerythrocytic [inside red blood cells] bacteria that we were looking at really wasn’t bacteria, it was this protozoan [single-celled organisms that include amoebas and the malaria organism] that we’ve discovered. And at first I thought it was babesiosis, and over the years, and a lot of money, and a lot of time, turns out it was actually a malaria-like organism with an extremely complex lifecycle that forms biofilm communities in the blood, it is a blood-loving parasite. And after mapping the genome of it, and we didn’t really name it until we had done that -- it’s probably a new genus, in the phylum [???]. You know, similar to malaria, similar to babesiosis, even more complex genetically, sort of in between a helminth [parasitic worm] and a protozoan.
So it’s really a complex organism. And because of the biofilm, and its slower rate of growth, it’s really not that invasive, it’s not like staph, or strep, or malaria. And it hides itself from the immune system, and hides itself from antibiotics, and likes to attach to the surfaces.
And over the years I evolved from using simple antibiotics like tetracyclines to more complex formulations that were really geared more towards malaria-like, or protozoa-like organisms. And that seemed to work a little bit better.
And then a year and a half ago I was introduced to Colin Campbell's work, John McDougall’s work, and I said, “You know, these patients that they claim are getting much better on a low-fat diet, a whole foods plant based diet, well these are the same patients I’m treating.” So we started to look at that analytical level and saying, “Hey, does this organism that we’re working on basically have a fat requirement?” Well it does. We were able to grow it in a culture, give it fat, and it grows a lot better with fat than without. Actually it doesn’t grow very well at all without any fat. And then we followed patients who went on a low fat diet, and we were able to calculate that the levels of this organism were decreased, sometimes disappearing, on a whole food, plant based, low fat diet. So, in the last year, my practice, I would have to say it is a lot more successful because I’ve combined this dietary lifestyle approach with traditional antibiotics. And that’s where I am today. Does that make sense?
Braman: So over what period of time -- what was it, eleven years -- that this has occurred?
Fry: Actually, you’d have to say that it’s been about 20 years. About 20 years ago I got interested in fatigue syndrome. Now let me explain something, as I saw these patients and talked to them and got their histories, you know, trying to really dig in to the real core of this whole problem, a lot of these patients with autoimmune disease start with fatigue syndrome. Most people don’t realize it, and other neurologists will acknowledge that, actually I was at a CCSVI [chronic cerebrospinal venous insufficiency] training session, at the neuroimaging center in Buffalo, and we were lectured by one of the leading MS experts -- he’s there, and he agrees, a lot of these MS patients have a prodrome [preceding syndrome] of fatigue, and it is really fatigue syndrome. So I feel that, you know, there is this spectrum of disease, starting with fatigue, that leads to fatigue, joint pain, muscle pain, brain fog, myalgic encephalitis. Then these people go on to develop a really true, full blown arthritis, or lupus, or, ALS [amyotrophic lateral sclerosis – Lou Gehrig’s disease], Parkinson’s, that sort of thing. So the mechanism of the disease is primarily for the neurodegenerative disorders, is a vascular sludging, and most probably vegetations that we can actually see in ultrasounds in these patients, and that is some work that we are very interested in, and we’re probably going to start a collaborative study with one of the centers on that one.
Braman: So with what kind of ultrasound, what kind of vegetations are you finding?
Fry: Well, they are doing -- this goes back to Paulo Zamboni’s work. I think he’s a vascular specialist at the University of Ferrara in Italy. His wife came down with multiple sclerosis and he wanted to find out what it was and hypothesized it was a vascular problem, and then after a lot of work developed an ultrasound technique and was able to visualize, using ultrasound, a defect in flow in either the deep cerebral veins or the petrosal veins of the brain or the internal jugular veins coming down from the brain. The next step to that was that he was able to show that in patients who had internal jugular vein obstruction or decreased flow he could go in with a balloon catheter and open this up. Some of these MS patients could get improvements and some dramatic improvements in their condition. Of course there’s a relapse rate with this that is actually quite high.
But it makes sense if it’s a microorganism that is growing there and you’re kind of, you know, clearing things up -- that would make a lot of sense. So now this has been repeated by Dr. Hubbard, who’s just recently submitted a 265 patient study showing similar results. Actually, that was a 6-month study. So these patients with MS have obstruction in the flow of the brain, and Dr. Hubbard used the word “swamp”. There’s reduced flow, bad flow, backflow. We feel the same way, that the brain is probably a sensitive organ or tissue. So if you change the flow environment in any way, whether it is less oxygenation, less nutrients, you are going to see some subtle changes and thus demyelination. It would be a subtle change, and I want you to know that they have documented remyelination in some of these patients where they have done this balloon procedure.
So here is a model of MS. In MS the researcher Roy Swank showed that patients with MS who are on a low fat diet, basically did not die of MS, and if they were on a regular diet they died of MS. And I think John McDougall was associated with the study, also out of University of Oregon, a five year study which should be near completion. I don’t know if he’s going to talk about it at ACAM meetings this week. I’m going to make sure I see that lecture, and I’m just curious to see if that data has been completed and if it shows the same thing that Roy was able to show. So if you tie in that concept with our concept it makes a lot of sense.
Now another interesting point, if we want to talk about MS and neurodegenerative disease, is that MS, there are about 75 papers dating back to the 1880‘s where physicians and laboratorians have discovered a malaria-like organism in patients with MS. There are 75 papers. There is a review article, a medical hypothesis, a two-part article that discusses this, and actually used antimalarial drugs in the 1920’s and early 1930’s in MS patients with significant improvement. But there was so much malaria in the U.S. at that time that they concluded that they really probably just had underlying malaria, and that was the cause of their MS. So if you put all the dots together it is a very fascinating argument if you believe that, in effect, this agent could be the underlying cause.
Braman: Wow! Now when you were talking about vegetations and ultrasound, can you actually see vegetations on the ultrasound image?
Fry: Yes, and when you see these vegetations, some are valves, and actually they categorize the type of vegetations. Or actually, they don’t use the word vegetations as Zamboni does, and I use that vegetation concept or idea. But there are growths, or filaments, or webs, or other structures that they see, that certainly aren’t normally found in the vasculature. And if you look at Zamboni’s work -- there is one you can see online -- Paolo Zamboni, you can pull it up, and there is an ultrasound and you can see the valve moving, but also you see a lot of other smaller and filamentous type material. Actually we have seen in blood samples filamentous material similar to that in patients with chronic fatigue. I think it is the same thing, and what we are seeing in the blood are really material that has just detached from the vasculature in long linear strands.
Braman: And has there been any work using -- you mentioned using a balloon to help clear things up -- what about things like thrombolytics [“clot-busting” or dissolving medications]?
Fry: Well, you know, thrombolytics are used in therapy on patients with proven vascular obstruction with clot. Now if you want to think of lumbrokinase as a thrombolytic -- you know, a lot of the alternative medicine folks out there are using lumbrokinase, serrapeptidase, and other agents like that to whittle away at these diseases. And of course you know Dave Berg who advocates a lot of this thinking, that it’s really...I think Dave’s old way of thinking about it is, some agents, whether it’s infection or say a heavy metal like mercury or something like that was, whether it was a virus or bacterial agent -- chlamydia or whatever -- was stimulating this coagulation phenomena producing a coagulation disorder. And of course he’s got the ISAC panel that he used to use to determine what type of coagulopathy these patients had and whether or not they had a hereditary disposition.
Now if you throw in this concept that these patients might have gross obstructive disease with a biofilm-forming protozoan, then it’s sort of...kind of brings all this thought together. So really in these patients they have -- for instance, in the CSF of fibro patients, they have brain fog -- I think that’s due primarily to sluggish flow either through some obstructive process due to these vegetations that I’m talking about, or even just the viscosity issue with a larger microorganism forming biofilm communities in the circulatory system.
To really mainstream [medicine] this is a radical concept, but the idea of biofilm communities elsewhere is no longer a radical concept. But I think a hematopoetic biofilm community of protozoans is a radical concept. But -- you know -- we have pictures. And, you know, the pictures are pretty astounding, pretty amazing. I developed this hypothesis years ago, that this is a biofilm problem, modified for additional techniques, and... there was, right in front of us. It was always there. And again, I’m not the first to report it either.
Braman: And so the biofilm -- they’re a web, or fibers, or sludgy blood?
Fry: Well, actually, not quite. Basically a biofilm...when we think of biofilm, bacterial biofilms... in training back in the ‘70s when I went to undergraduate school we called it “the slime layer.” And microbiologists have known about slime layers and syncytial microbes for a long, long time. And the best analogy would be to think of a slug that you see crawling around, and you know that slimy stuff on there, it’s a similar material. It’s a mixed mucopolysaccharide, there is hyaluronic acid in it. And actually the biofilm is a very complex structure with a lot of function attached to it. And so DNA is the -- I think the “rebar” for biofilm. DNA is not only an informational molecule, it is also a structural molecule. So with this rebar of DNA, that’s basically a grid system. Secreted are mucopolysaccharides, peptides, that sort of thing. So it is able through the biofilm -- it can actively transport nutrients in and export noxious byproducts from metabolism out.
The only problem is that it also excludes antibiotics and drugs. Also biofilms prevent the microorganism from being even seen by the immune system, and we think that is what’s going on with these patients. So if you have ever heard of the Jarisch-Herxheimer [clinical worsening due to the infectious agent dying off] reaction, we think what is going on in a Jarisch-Herxheimer in these patients.... I mean usually when you treat these patients with drugs, say a lupus patient with Plaquenil, they feel terrible initially and it flares up their disease. So what’s going on in that particular situation, I believe, is that the drug is getting to the organism somewhat and weakens it enough so that its antigens are exposed on the surface, and system can see this enough to produce a profound inflammatory response. And I think that is what the Jarisch-Herxheimer actually is.
It’s not necessarily cellular death; it’s really the cytokines produced by the immune system trying to destroy the pathogen, but it can’t really get at it very well. And a real limitation to therapy is this Jarisch-Herxheimer reaction or inflammatory response. And, possibly, if we found the greatest drug in the world to kill this microorganism, the use of this drug would be limited because of this profound inflammatory response once you start to get at that organism.
Braman: How are you currently treating this and what results are you seeing?
Fry: Well I’m actually pretty conservative, I’m really kind of the McPherson Brown… you know, go slow, steady, conservative approach. Let’s not get people so debilitated they can’t go back to work. Almost all of these patients are low in Vitamin D. So the first thing I start patients on is Vitamin D. Some patients start Vitamin D -- they get ill when they start, then they start feeling better. So, in terms of nutrition, vitamin D. And then I put them on a low-fat diet. And the amazing thing -- the majority of my patients who initiate an ultra low-fat diet have a Herxheimer reaction. So we can actually explain that now because we’ve weakened the microorganism. It probably needs fat because of this high energy requirement to produce this biofilm in a harsh host environment, and as we restrict fats it weakens the organism, the immune system can see it, and we get a flare.
A lot of my patients have a flare reaction, or Herxheimer reaction, when they change their diet to a low-fat diet. And then I start with tetracyclines -- usually doxycycline or minocycline. I like those two because it hits a lot of other microorganisms at the same time. They’re pretty safe, they’re inexpensive, and both drugs are also antimalarial drugs. They’re used prophylactically and for application for treatment around the world for malaria. So they actually have antiprotozoal activity that most people aren’t aware of.
Then I proceed to azithromycin because that seems to work in some patients. It’s a safe drug. You can take it for long periods of time without major problems. And then on to more of the traditional antimalarial drugs like Plaquenil in combination with tetracyclines -- that’s been done for a long, long time. I think the hesitancy in the rheumatology community for minocycline or tetracycline: 1) is they’re not sure how it’s working, and 2) these patients have a flare or Herxheimer reaction that’s very hard to manage. And that may be one of their observations, not really understanding the underlying mechanism and what’s going on there.
I thought for a long time these patients may have had babesiosis because it seemed to look like it in the microscope and I was using azithromycin and atovaquone and patients have profound Herxheimer reactions on that combination, but once they get through it they seem to actually do very well. And we’re always looking at other drugs in the laboratory, and that’s another story -- what drugs seem to work in the lab. I don’t think our model of disease is developed enough...we use microtiter plates, we’re able to culture it. I just don’t think our model of disease is good enough yet to make great conclusions as to invitro [in the lab] sensitivity. I’m pretty sure that people have different strains of this microorganism. One drug might work on one person, and not on another person. So I suspect that there are really significantly different strains of this organism out in the community.
Braman: So you are able to culture this and grow this in the lab?
Fry: Oh, no, we can grow it. There is no question we are growing it. So we’re growing it quite well, it’s just that I’m not really happy -- there are a lot of technical issues with drug sensitivity. A lot of these drugs require second order kinetics. They have to go through the liver, so it is just a matter of time and money to really get serious about doing drug sensitivity studies. But we have some interesting data created now, and confirmed by PCR [polymerase chain reaction – a technology for measuring very specific DNA sequences] so.... Really what we developed is a biofilm assay for this organism, I mean, that’s really what we’re measuring now. And those studies are really backed up by PCR, quantitative PCR.
Braman: So are you actually able to eradicate it in people, or is it an indefinite...?
Fry: We cannot eradicate it in patients, as far as we know, and we cannot eradicate it completely in the test tube yet with any known agents that could be delivered in therapeutic doses. Now we have some patients who are feeling very well, who, where by our normal procedure, we can’t find evidence of disease, but if we go through a sample and keep looking, and looking and looking we can find some. Most patients that are ill, with our technology it’s very easy to detect disease. These patients that are doing much, much better, who are on a low fat diet, we’re able to find it, though rarely in those patients. So I cannot say that we have eradicated it in any patients. My patients who do great, who are on a low fat diet, if they start eating a regular American diet again, they relapse. So I have not cured anybody.