This is from a radio program broadcast on 1-16-00. ========================================================= Host: Roger G. Mazlen, M. D. Guest Dr. Larry Klapow, PhD Dr. Mazlen: To kick off the new millennium with a good show that you’ll find of great interest and great importance, I’m talking today with Dr. Larry Klapow, a Ph. D. in Invertebrate Biology who’s in Burlingame, California near San Francisco. Good morning Larry, welcome to our show. Dr. Klapow: Good morning, Roger, I’m glad to be here. Dr. Mazlen: Can you tell our audience something about this suspected new parasite that you’ve found in a percentage of patients with Chronic Fatigue Syndrome? How’d you find it? Dr. Klapow: Well, Roger, it came about as a result of a conversation I was having with an immunologist friend of mine, Dr. Vincent Marinkovich, here in Redwood City, California. He was treating a CFS patient we thought might have a roundworm infection. The patient had a low-grade eosinophilia and some unusual rashes on the torso that suggested the possibility of threadworm disease. Antibody tests and stool tests were negative. I thought about this for a while and I know that some chronic parasites migrate between the digestive tract and the respiratory tract and some of them are coughed up in sputum. So I looked at the sputum and that’s where I found it. I called the new parasite “Cryptostrongylus pulmoni”, that’s a provisional name and it means “the hidden lung worm”. Dr. Mazlen: That’s pretty appropriate in terms of what you say. Dr. Klapow: It definitely is, Roger. It’s very difficult to find. And I hope other people will start looking for it. In fact, I’ve put together some material that I think can help them. Dr. Mazlen: You recently completed a small blinded study in cooperation with a small number of CFS doctors including Dr. Anthony Komaroff in Harvard. You’re now doing a larger blinded trial and you’re also trying to develop a clinical test for the parasite. But for these other investigators and clinicians, can you tell us what does the parasite look like and how can they find it? Dr. Klapow: You can identify the parasite, the female by its mouth parts and the male by its very intricate reproductive structure. This parasite is very small. The female is less than a millimeter long and the male is about a third that length. So, in addition to being small there’s also a lot of difficulties. The specimens I usually pick up are naturally expelled in sputum and they’re usually very decayed and rare and because of this you need very specialized imaging techniques to find them. They’re not expensive techniques, they’re just specialized. In any case I wanted to help people look for this parasite and so I put together a website which describes how to find it in great detail. It also includes anatomical drawings. I can give you the website address if you like. Dr. Mazlen: Yes, give us the address right now, that’ll be great. Dr. Klapow: OK, I’ll give you my own email address and then I can post the other rather longer address for people who contact me. My email address is email@example.com. Dr. Mazlen: Now, this is really important because this introduces a whole new dimension about Chronic Fatigue Syndrome and its possible relationship to roundworm infestation. Can you tell us so far, at least, as you’ve been looking, what percentages of Chronic Fatigue Syndrome patients are turning out to be positive for this worm? Dr. Klapow: Yes, I find the parasites in about 40% of three-day sputum samples from CFS patients. However, I have to tell you that yields are very low. In fact, they’re so low that I think I’m probably missing as many positive patients as I’m finding. The problem here is that over 80% of the positives I get are represented by only one identifiable specimen. So just by chance it looks like I’m missing a fairly high percentage. Dr. Mazlen: So, the prevalence can be a lot higher and this, of course, stirs some very great interest in terms of causation and etiology which we’ll go into later. Can you tell us anything about the blinded trials so far? Dr. Klapow: Yes, I did a small blinded trial in cooperation with a number of doctors including Dr. Anthony Komaroff at Harvard and here are the results. I think they’re interesting but you judge for yourself. 5 of the 11 patients were positive while all 6 controls were negative. Now, it’s a small trial but if you were trying to do as well by guessing, say by just tossing a coin, you’d only do as well as I report here in about 1 in a 100 tests, so it’s a very hard thing to do by just guessing. The results of this small trial can be used to devise an experimental design for a large trial that could give a statistically significant result and going through that exercise suggests that between 50 and 80 samples will be needed. Now, it may take some time to process these samples microscopically. It’s now taking me somewhere between 50 and 100 hours to find a single positive patient so I think the progress will be slow, that is unless we can get something more rapid going in the form of a PCR test. Dr. Mazlen: Well, I certainly congratulate you though for the effort that you’re making because this is totally important to patients for their prognosis and recovery ultimately. There’s a lot more to learn and, of course, we’re going to go into that and you mentioned the PCR test and that you have some arrangements whereby this can be developed and hopefully you’ll get some funding to help this along soon. If anybody in the audience is interested in helping in this regard they can reach me at firstname.lastname@example.org which is my email address and I’ll forward it on to Dr. Klapow. Larry where do you think these parasites might be coming from? Dr. Klapow: Well, Roger, they have some specialized anatomical structures that suggest that they’re related to parasites of animals that live in the jungles of Southeast Asia. In fact, there’s been somewhat of a history of hard to diagnose parasites coming out of that area and being brought back to ”Western” countries after periods of warfare. It happened in the Victorian era when French soldiers were returning from this area and brought back the chronic parasite Strongyloides stercoralis to Europe where it was first diagnosed in 1894. It also happened again in World War II. This time British soldiers became infected while they were imprisoned in Burma returned to England and 30 years later, in 1974 they were diagnosed with chronic parasites they had gotten while they were in prison. It’s kind of a testament to how difficult some of these parasites are to find and treat. I would like to look at people who’ve been to Southeast Asia and I think I plan to do that as soon as I finish with the large trial I’m doing on CFS patients now. Dr. Mazlen: It’s a natural sequitur because you’re going to be having a chance to look at all of the veterans of the Viet Nam era who either served in Viet Nam or Cambodia or neighboring areas. Dr. Klapow: That will happen, I think, rather quickly if I can get the PCR test going. Dr. Mazlen: You say it might be coming from this source and that’s a possibility. How is it contracted? How do you get it then? Dr. Klapow: I’m really not sure. What I can tell you is this. I’ve never seen a fresh transmissible stage of the parasite in any sputum sample I’ve seen so far. I’ve done a couple of hundred samples at this point. So I don’t think there’s any evidence right now of casual transmission. But roundworm parasites are typically acquired by eating contaminated food, but an outbreak of Cryptostrongylus infection, if it were transmitted in this way, would look very different then a typical food poisoning incident where people get sick within a couple of hours after eating. Dr. Mazlen: That’s due to the long latency that you mentioned. Dr. Klapow: Cryptostrongylus is very small but it produces a larvae which is very large so there’s an implication here that it must be reproducing very slowly and possibly has a very long latency time. Of course, we know that the outbreak of Chronic Fatigue Syndrome usually take place over several months and in some cases a couple of years and that I think would be consistent with the possibility of a food borne infection with a very long latency period. Dr. Mazlen: Well, now we’re going to turn to the clinical side. Most of the time that doctors are looking for parasitosis, they look to see elevated eosinophil and serum IgE, or immunoglobulin E, levels in patients. Isn’t this usually the case? Dr. Klapow: Yes, but that’s the first question that I get from doctors when I tell them that I found what I think is a new species of roundworm parasite. Where’s the elevated IgE? And the answer is elevated IgE is mainly apparent in acute roundworm infections. With time, the chronic parasites are able to suppress the IgE response and many of them produce a clinical picture where the patients either have normal or lower than the normal average level of IgE and, in fact, that’s the picture you see in CFS and in all the studies I’ve reviewed, IgE is lower in CFS patients than in healthy control populations. Dr. Mazlen: Here I want to interject that I’m part of the new study looking into C. pulmoni in CFS patients and one of the things that prompted me to call you and talk to you about getting involved is the fact that I had been seeing low IgE levels, low eosinophile counts in patients that I thought were inappropriate. Dr. Klapow: In fact, there was a paper that’s a few years old in the Journal of Chronic Fatigue Syndrome that indicates that if you correlate IgE and eosinophil levels with the number of symptoms the patients report, the sicker they are the lower the IgE and eosinophil counts and that’s a statistically significant relationship. Dr. Mazlen: And I see it and it seems to be borne out. Now, what do you think is suppressing IgE in this CFS or Chronic Fatigue Syndrome patients? What’s the mechanism? Dr. Klapow: Well, I think the mechanism may involve the cell marker CD23 which suppresses IgE. There are a couple of other things that activate CD23, the IgE suppresser and those are active herpes viruses and some of the TH1 cytokines, particularly interferon-gamma and the 2’-5’A, the activator of the latent RNase enzyme. Both herpes viruses and 2’-5’A, as you know, are highly elevated in CFS patients. In fact, it looks like some roundworms may be using chronic viruses as cofactors to help perpetuate their own survival. Dr. Mazlen: That certainly rings true from what I’ve seen clinically and that leads us to another question. If a lot of Chronic Fatigue Syndrome patients have allergies, they should have elevated IgE levels but a lot of them, as we were just saying, don’t. It seems to fit the model you propose of a suppresser. Dr. Klapow: Yes, there are some doctors, in fact, that think allergy is a risk factor for getting a roundworm infection and that’s because patients who tend to produce too much IgE to non-specific stimuli, harmless things, may not have enough reserves left over to fight off the parasites so they get a foothold, and in fact, initially, you can even see patients who report increased allergies, but later on when they’re diagnosed with CFS and the presumptive parasite, if we may go so far and speculate, has suppressed their IgE response and the values come out clinically low. Dr. Mazlen: Now, this brings us to a leading question, which, obviously is a speculation, but that’s all right because that’s what this show is about. We want to raise issues and have other people contribute to answering them as well. There seem to be many infectious agents that have been proposed as being possible etiological agents for Chronic Fatigue Syndrome. None of them have held up specifically as a single causative agent. What do you think about this roundworm infection, c. pulmoni, is it a primary infection or is it just another opportunistic organism? Dr. Klapow: Well, I don’t know if it’s a primary cause of CFS. We’ll just have to have to go through the rules of Koch’s postulates and see how far we can get. I think it’s an interesting candidate for a possible primary agent. I don’t think it’s an opportunistic infection. Opportunistic infections are usually airborne and are present everywhere. They’re just waiting for our immune systems to be weakened before they establish a chronic infection. Cryptostrongylus doesn’t seem to be ubiquitous. If I’m right about the taxonomy, it looks like it’s coming out of a particular geographic area. They’re are also a number of things that I think can connect roundworm infection to the major physiological systems that malfunction in CFS. And they have to do with the wide variety of physiologically active agents roundworms are able to secrete. Dr. Mazlen: We’re going back now and talking about the hormones that these roundworms secrete, namely vasoactive intestinal polypeptide, which is known as VIP, and hippocampal cholinergic neurostimulatory peptide which is known as HCNP, and what they do and Larry, what do these hormones cause? What do they do? Dr. Klapow: Well, VIP is involved in regulating blood pressure and blood flow. It’s important in regulating blood flow to the brain. It’s believed to be implicated in orthostatic intolerance from which a number of CFS patients suffer. And, it also controls hypothalmic CRH, a hormone that’s ultimately responsible for the level of cortisol in the blood which is suppressed in CFS and it’s also suppressed in chronic roundworm infections. And the other one, HCNP, is a limbic system neuropeptide and it’s believed to be involved in memory and immune function. When it goes wrong in areas that have Alzheimer’s lesions, there are cognitive symptoms. In fact, some doctors have suggested that CFS looks in some respects like a reversible form of Alzheimer’s. Dr. Mazlen: It seems like that sometimes. Dr. Klapow: Well, the bad news is that it bares any resemblance to that disease. *What good news there is, is that the cognitive symptoms come and go, without apparently doing permanent damage. I think it is a reasonable hope that increasingly effective treatments for CFS will be found in time to substantially help most of those who now suffer from this difficult and often misunderstood disease. *Added to transcript by Dr. Klapow after the show. Transcribed by Carolyn Viviani email@example.com Permission is given to repost, copy and distribute this transcript as long as my name is not removed from it. © 2000 Roger G. Mazlen, M. D.