Treating Hidden Viral Infections in CFS/FMS Can Sometimes be a Cure
Used with permission from the book: "From Fatigued to Fantastic!" 3rd edition (Penguin/Avery October 2007)Summary:
People with CFS/FMS are at high risk of having multiple viral and antibiotic sensitive infections because of their immune system dysfunction. That people usually have not just one, but several, infections simultaneously is significant. It suggests that although these infections may be a trigger for the illness in some cases, most of the infections occur because of the illness, setting you up for multiple and sometimes unusual infections that persist. These infections may then drag you down, further suppressing your immune system.Fortunately, most people improve (and often get very healthy) by simply treating sleep, hormonal, nutritional, and yeast problems. Once these areas are treated, your body can often eliminate many persistent infections by itself. Some people, though, have infections that need treatment with antivirals and/or antibiotics, and almost all folks with CFS/FMS need anti-fungals (candida) treatment.
We are very excited about recent research by Professor Montoya which showed that a group of CFS patients with evidence of chronic viral infections with HHV 6 virus improved dramatically with 6 months of the new antiviral Valcyte. Our experience now with 100 patients who have gone through the Valcyte treatment at the Fibromyalgia and Fatigue Centers has shown that ~ 70% of these have improved dramatically. Some that I've talked to have considered themselves to now be healthy. I think this treatment is a dramatic leap forward for a significant subset of those suffering with CFS and Fibromyalgia. See Natural Immune Boosters and Antivirals.
Read on if you'd like more detailed information.
How can you tell if you need such treatments?
First, I would try the other approaches discussed in this book. I would consider antiviral (and/or antibiotic) treatments if the following symptoms persist:
 | Predominantly flu-like symptoms, with debilitating fatigue and little or no pain or fever. People with these symptoms are more likely to have an underlying persistent viral infection, such as HHV-6, CMV, or EBV. In these cases, special blood tests for HHV-6 (an HHV-6 IgG level by IFA drawn at Quest labs and sent out to Focus labs—consider valcyte if 1:320 or higher) and CMV (a CMV IgG-consider valcyte if 4.0 or higher) can help identify who is a candidate for the antiviral Valcyte (see details below). |
| A fever over 98.6°F—even 99°F—and/or lung congestion, sinusitis, a history of bad reactions to several different antibiotics (people misinterpret this "die-off" reaction as being an allergic reaction), scabbing scalp sores or other chronic bacterial infections. People with these symptoms seem to be more likely to have bacterial, mycoplasma, or chlamydia infections that respond to special antibiotics. |
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Viral Infections
Human herpes virus type 6 (HHV-6) is a virus that is related to the Epstein-Barr virus (EBV), cytomegalovirus (CMV), and also to the herpes viruses that cause cold sores and genital herpes. All of these are in the Human Herpes Virus family and stay in the body (usually in an inactive latent form for EBV, CMV, and HHV-6) for the rest of your life. Usually HHV-6 is transmitted like the common cold, and most adults have had HHV-6, as well as EBV and the cold sore virus, by the time they are twenty years old.The problem with lab testing for infections in CFS
Unfortunately, there is no test that clearly distinguishes old dormant infections from viral reactivation. When you first have an infection, antibodies in the IgM family ("M" antibodies are like your bodies storm troopers) are elevated for 6-12 weeks—telling doctors that you have an active new infection. After that time, the IgM test will be negative. The IgG antibody levels then stay elevated ("G" antibodies are like regular troops, suppressing the latent infection) for the rest of our lives. Because of this, when you check the standard IgG antibody testing almost everybody (including healthy people) tests positive for EBV and HHV-6 and many will test positive for CMV. That the IgG test is elevated, however, does not tell you if you have an active infection because of viral reactivation or simply an inactive, dormant infection. Other tests available to your doctor, such as PCR testing, are also still unreliable for a number of reasons and the IgM test will not be positive in the vast majority of those with reactivated viral infections.
Nonetheless, these infections are common in CFS, and the available IgG test may still offer useful information. Unfortunately, despite all of the data to the contrary, most doctors are not familiar with the research and still mistakenly think a negative IgM antibody test confirms that there is no active infection. Because most physicians are not aware of this research, and it may be important for your doctor to know about, I invite the more scientifically oriented reader to read Sidebar 1—"Research on Viral and Antibiotic Sensitive Infections in CFS/FMS."
Sidebar 1 - Research on Viral and Antibiotic Sensitive Infections in CFS/FMS
• A study by Dylewski et al in the New England Journal of Medicine demonstrates that in immune compromised patients, as occurs in CFS/FMS, active infections correlate with elevations in IgG antibodies without elevations of IgM antibody and that a lack of elevation of IgM is not useful in these patients as a way to rule-out active infection. A high clinical suspicion must be maintained and implementation of anti-infective treatment should be based on elevated IgG levels.22
• In addition to mycoplasma, numerous studies have also demonstrated other bacterial and viral infections such as EBV, CMV, HHV-6, and enterovirus in CFS and FM patients that cause or contribute to the symptoms. The research also demonstrates that these infections are present and that an active infection correlates with an elevated IgG antibody, despite the lack of IgM antibodies.22-33 As with mycoplasma infections(see below), because these infections are generally not acute but rather reactivation of an old infection, an elevation of IgM antibodies is typically NOT seen with active infections of EBV, CMV, HHV-6, Borrelia (Lyme) and enterovirus.23-33 Because of the immune dysfunction seen in CFS, there may even be a lack of IgG antibodies present despite the presence of an active infection.30,34,35
• Immune suppressed patients have also been shown to be helped by anti-viral therapy in a number of studies.36-40
• It is clear that multiple infections are present in CFS/FMS patients. For example, one study found that 52% of CFS patients had active mycoplasma infection, 30.5% had active HHV-6 infection, and 7.5% had Chlamydia pneumonia infections vs. only 6%, 9% and 1% of healthy people, respectively. They conclude, "The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients."41
Unfortunately, despite all of the data to the contrary, most doctors are not familiar with the research and still mistakenly think a negative IgM antibody test confirms that there is no active infection. Getting past the misconception that these infections are not active if the IgM test is negative is important, as we finally have treatments that are effective against many of these infections. Let's look at some of the more important ones.• A study by Dylewski et al in the New England Journal of Medicine demonstrates that in immune compromised patients, as occurs in CFS/FMS, active infections correlate with elevations in IgG antibodies without elevations of IgM antibody and that a lack of elevation of IgM is not useful in these patients as a way to rule-out active infection. A high clinical suspicion must be maintained and implementation of anti-infective treatment should be based on elevated IgG levels.22
• In addition to mycoplasma, numerous studies have also demonstrated other bacterial and viral infections such as EBV, CMV, HHV-6, and enterovirus in CFS and FM patients that cause or contribute to the symptoms. The research also demonstrates that these infections are present and that an active infection correlates with an elevated IgG antibody, despite the lack of IgM antibodies.22-33 As with mycoplasma infections(see below), because these infections are generally not acute but rather reactivation of an old infection, an elevation of IgM antibodies is typically NOT seen with active infections of EBV, CMV, HHV-6, Borrelia (Lyme) and enterovirus.23-33 Because of the immune dysfunction seen in CFS, there may even be a lack of IgG antibodies present despite the presence of an active infection.30,34,35
• Immune suppressed patients have also been shown to be helped by anti-viral therapy in a number of studies.36-40
• It is clear that multiple infections are present in CFS/FMS patients. For example, one study found that 52% of CFS patients had active mycoplasma infection, 30.5% had active HHV-6 infection, and 7.5% had Chlamydia pneumonia infections vs. only 6%, 9% and 1% of healthy people, respectively. They conclude, "The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients."41
HHV-6
A reactivated HHV-6 viral infection is present in many patients with CFS. A study in the Annals of Internal Medicine found 70 percent of patients with CFS had active HHV-6 infection.42 In another study of HHV-6 in CFS patients, 89 percent with very high HHV-6 IgG antibody levels of 1:320 and above were found to have active infections by cell culture. To compare, most healthy adults with an old, inactive infection have levels of 1:40 to 1:160. Though not all of the studies were able to document the infections, as CFS expert and Harvard Professor Anthony Komaroff notes in his recent review "the great majority of studies have found evidence of active replication of HHV-6 more often in patients with CFS than in healthy control subjects."43
When HHV-6 is present, it seems to affect the immune system's natural killer cells that are critical in fighting infections and are also often malfunctioning in CFS. Natural killer cell function is described in what is called lytic units—which means the ability of cells to lyse, or break down, foreign invaders. An average person has a lytic unit level of 20 to 250, with over 80 percent of healthy people having more than 40 units. However, in people with CFIDS, the mean natural killer lytic unit level is just 12 units. With your immune system so low, the reactivated HHV-6 can then also cause reactivation of the Epstein Barr virus. In addition, both HHV-6 and EBV can suppress immune function, and HHV-6 can suppress your body's ability to fight fungal/yeast infections as well.
Until recently, there was no readily available treatment for HHV-6. Even though it is related to other herpes viruses, HHV-6 is resistant to acyclovir (Zovirax), Valtrex, famciclovir (Famvir), and the other antivirals that are commonly used for herpes infections. Fortunately, there is a new and promising oral antiviral called Valcyte that has been shown in early studies to be very beneficial in CFS patients who have both HHV-6 and EBV viruses. Unfortunately, this drug can have significant side effects, although it causes no problems in most CFS patients, and is very expensive. If you have an open-minded doctor and are interested in exploring Valcyte treatment, the information in the Sidebar 2 may be helpful to your physician.
Sidebar 2 - Diagnosing and Treating Reactivated HHV-6 infections in CFS
In a recent study by Professor Jose Montoya of Stanford University, CFS patients were treated with the new anti-viral drug Valcyte if they had elevated IgG tests for HHV-6 and EBV and had at least 4 of the following symptoms-impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue, and symptoms consistent with depression. In their first study of 12 patients, 9 out of 12 (75 percent) patients “experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activities. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320… serious adverse events were not observed among the 12 patients.”44
I had the pleasure of speaking with Professor Montoya in January 2007 to get further details on his treatment protocol. In CFS patients whose symptoms began with a flu-like illness and who have an EBV VCA IgG antibody level of at the least 1:640 plus an HHV-6 IgG antibody of at least 1:640 (or 1:320 if the EBV is at least 1280) he treats as follows (I now use the blood test parameters noted earlier in this article):
1. Valcyte 900 mg 2x day is given for 3 weeks, then
2. Valcyte 900 mg 1x day is given for 23 weeks.
To monitor for toxicity (which he has not found to be a problem in CFS patients) he does the following testing:
CBC and Chemistries (BUN, Cr, ALT, AST) twice a week for three weeks, then once a week for three weeks, then every other week for three weeks, and then monthly while on the treatment.
He avoids using Valcyte in those with severe neuropathic (nerve) pain in their hands as well as in patients with inadequate kidney function or who have white blood cell counts less than 3,500, as a potential toxicity is bone marrow suppression. He found that all patients who improved initially flared their symptoms from about the second to the fourth weeks of treatment-often leaving them housebound for that two week period. Most noticed significant improvement beginning at about three months into treatment. The patients I have spoken with who have taken it have been very pleased, but a few have developed recurrent symptoms when they stopped the medications after six months and are considering repeating the treatment. Though there is the potential for toxicity from this medication, current experience suggests that it has not been a major problem in the CFS population. In our experience, those treated with the "SHINE protocol" in addition to the Valcyte often do not get the initial worsening of symptoms. It may take 4 months to start seeing the benefit.
This treatment is very promising with the main limiting factor now being its cost. Sixty 450 mg tablets (a 1 month supply) costs ~ $ 2,000 from Consumers Discount Drugs (1-323-461-3606) and is available from Canada by mail for $1,500. This makes the 6 month cost ~ $10,000-13,000. Prescription insurance has usually covered the cost of the medication.
EBV and CMVIn a recent study by Professor Jose Montoya of Stanford University, CFS patients were treated with the new anti-viral drug Valcyte if they had elevated IgG tests for HHV-6 and EBV and had at least 4 of the following symptoms-impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue, and symptoms consistent with depression. In their first study of 12 patients, 9 out of 12 (75 percent) patients “experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activities. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320… serious adverse events were not observed among the 12 patients.”44
I had the pleasure of speaking with Professor Montoya in January 2007 to get further details on his treatment protocol. In CFS patients whose symptoms began with a flu-like illness and who have an EBV VCA IgG antibody level of at the least 1:640 plus an HHV-6 IgG antibody of at least 1:640 (or 1:320 if the EBV is at least 1280) he treats as follows (I now use the blood test parameters noted earlier in this article):
1. Valcyte 900 mg 2x day is given for 3 weeks, then
2. Valcyte 900 mg 1x day is given for 23 weeks.
To monitor for toxicity (which he has not found to be a problem in CFS patients) he does the following testing:
CBC and Chemistries (BUN, Cr, ALT, AST) twice a week for three weeks, then once a week for three weeks, then every other week for three weeks, and then monthly while on the treatment.
He avoids using Valcyte in those with severe neuropathic (nerve) pain in their hands as well as in patients with inadequate kidney function or who have white blood cell counts less than 3,500, as a potential toxicity is bone marrow suppression. He found that all patients who improved initially flared their symptoms from about the second to the fourth weeks of treatment-often leaving them housebound for that two week period. Most noticed significant improvement beginning at about three months into treatment. The patients I have spoken with who have taken it have been very pleased, but a few have developed recurrent symptoms when they stopped the medications after six months and are considering repeating the treatment. Though there is the potential for toxicity from this medication, current experience suggests that it has not been a major problem in the CFS population. In our experience, those treated with the "SHINE protocol" in addition to the Valcyte often do not get the initial worsening of symptoms. It may take 4 months to start seeing the benefit.
This treatment is very promising with the main limiting factor now being its cost. Sixty 450 mg tablets (a 1 month supply) costs ~ $ 2,000 from Consumers Discount Drugs (1-323-461-3606) and is available from Canada by mail for $1,500. This makes the 6 month cost ~ $10,000-13,000. Prescription insurance has usually covered the cost of the medication.
The roles of EBV (Epstein Barr Virus) and CMV (cytomegalovirus) in CFIDS are also not clear. It is not uncommon for antibody levels of these viruses to also be elevated in people with chronic fatigue syndrome. However, we do not know if this elevation reflects an old inactive infection verses an ongoing infection with these viruses. Given the findings with HHV-6 and the drop in EBV antibody levels after treatment, I am inclined to believe that reactivation is occurring with these viruses as well. As discussed in reference to HHV-6 infection, I have not found the anti-viral Valtrex to be helpful in treating CFS symptoms and no longer use it. Valcyte still holds much greater promise and is effective against HHV-6, CMV, and EBV. As the HHV-6 seems to trigger reactivation of EBV, it is possible that suppressing the HHV-6 infection is enough to allow the body to also overcome the EBV infection as well.
In addition to Valcyte, there are also a number of other treatments that may be very helpful in fighting CMV, HHV-6, and other infections.
Natural Immune Boosters and Antivirals
1. Thymic protein A, marketed under the brand name ProBoost is an excellent natural immune stimulant. Although not a hormone, thymic protein A mimics the natural hormone produced by the thymus, the gland that stimulates the immune system. I find it to be extraordinarily effective in fighting common acute infections of any kind that seem to pop up and recommend it be in everyone's medicine cabinet. In fact, whenever my kids get a cold, the first thing they say is "Dad, where's the white powder?" (the ProBoost)!Although taking it for 1 to 3 days will quickly eliminate most acute infections, for the chronic infections of CFIDS, 1 packet three times a day for 3 months is needed. In one study, this dropped EBV IgG levels by 70 percent after 3 months in CFS patients.
2. Silver is a remarkable anti-infectious agent against a very broad spectrum of infections. For sinusitis, there is an excellent silver nose spray called Argentyn 23. In low doses, this mineral is an anti-infectious agent against both viral and bacterial infections, and liquid silver can even be used orally for many types of difficult-to-treat chronic infections. Silver also works well in combination with the prescription sinusitis nose spray, which your physician can call into ITC Pharmacy (303-663-4224).
The problem with using the wrong types of silver is that if a person overdoses it can build up in their body, and turn the skin permanently blue (very Smurfy, but not a good idea). Called argyria, it is not dangerous, but it is odd looking. Because of this, it is important to use safe forms that are very small molecules, so they don't build up in the body. I use the Immunogenics brand of silver liquid and nose spray. These have never caused the blue skin problem. (Directions for silver use.)
In addition to ProBoost and Silver, some other excellent immune boosters include:
1. Leuko-Stim. This mix mostly stimulates immune function, but the olive leaf may also have anti-viral properties. It contains Olive Leaf Extract, Beta 1,3, Glucan, Maitake Mushroom Extract and Arabinogalactan (Larch).
2. Maitake D Fraction 30. Contains 330 mg of maitake mushroom and extract (an immune stimulant).
3. Anti-Viral. This natural combination contains a mix of Milk Thistle Extract (80 percent Silymarin), Phylanthus amarius, Phylanthus uraria, Monoammonium glycyrrhizinate, L-Lysine, N-Acetyl L-Cysteine, Astragalus Herb Powder, Lactoferin, Olive Leaf Extract, Dionea (Venous Fly Trap extract), and Selenium (Selenomethionine).
If a chronic viral or bacterial infection is suspected, consider treating it with three months of Anti-viral regimen, Leuko-Stim or Maitake, plus ProBoost. Adding the silver solution may also help. These natural supplements can be taken on their own or with antibiotics and antivirals. Though these are more expensive than many other natural supplements, they can be very helpful in fighting these infections and are well tolerated. You'll see effects from treatment in about three months.
• Lysine is an amino acid (one of the building blocks of protein) that inhibits oral and genital herpes viruses by depleting arginine, another amino acid that the virus needs to grow. It is not known whether Lysine also inhibits EBV, HHV-6, or CMV, but these viruses are all members of the herpes family. Lysine is safe and inexpensive. The recommended dosage is 1,000 milligrams three times a day. Arginine is used by the body to make both nitric oxide and growth hormone. Decreasing arginine may therefore also decrease excessive nitric oxide activity in CFS. The down side is that it may also decrease Growth Hormone—which is too low in CFS. Because of this, it may be reasonable to take Lysine for 6 months, but I would not use it long term in CFS.
• Another treatment that may be helpful is Vitamin C. High doses of 15 to 50 grams of vitamin C, administered intravenously, are often dramatically helpful for CFS when given in the intravenous nutritional therapy your doctor may administer called Myers Cocktails or Standard IVs (available at the Fibromyalgia and Fatigue Centers and at many Holistic physicians' offices).
• In addition, your clotting system may be activated by several infections, making it difficult to eliminate the viruses. Using the anti-clotting treatment that we discuss in From Fatigued to Fantastic! can also make it easier for your body to eradicate infections.
Sidebar 3 - Natural Antiviral Treatments Available by Prescription
There are two treatments that deserve special mention. The first is a natural anti-viral derived from animal livers. Called Nexavir (formerly sold as Kutapressin), it is given by daily injection, either subcutaneously or intramuscularly. In my practice, I have seen dramatic improvement with regular use of the Nexavir. However, daily injections are a must, and the few patients who only used it three times a week did not get much, if any, benefit. The downside is that it costs $19 a day, and the symptoms may return when the injections are discontinued.
The second natural prescription treatment is gamma globulin. These are the actual antibody infection fighters derived from the serum of numerous blood donors. The serum is first treated to kill off any infections the donors may have had and then the antibodies are harvested. Although these antibodies can be helpful against both bacterial and viral infections, in patients with latter we have seen a die off reaction (initial flaring of symptoms) with each injection of gamma globulin. I am now advising patients to start with the Nexavir first and add the gamma globulin 1-3 weeks later. I recommend 2 cc be given intramuscularly weekly or 4 cc IM every other week for 6 doses, and then as needed. Although it can also be given through an IV, this delivery method is very expensive and does not seem to bring any additional benefit.
Because Valcyte has been so effective and can eliminate the infection, I rarely prescribe the Nexavir anymore. The gamma globulin IM injections are wonderful in these illnesses, and a recent study suggested that they even help the nerve pain present in a third to half of those with fibromyalgia (though in that study they gave it IV). If your illness began with an infection, or persists despite other therapies, you may wish to discuss these treatments with your doctor
There are two treatments that deserve special mention. The first is a natural anti-viral derived from animal livers. Called Nexavir (formerly sold as Kutapressin), it is given by daily injection, either subcutaneously or intramuscularly. In my practice, I have seen dramatic improvement with regular use of the Nexavir. However, daily injections are a must, and the few patients who only used it three times a week did not get much, if any, benefit. The downside is that it costs $19 a day, and the symptoms may return when the injections are discontinued.
The second natural prescription treatment is gamma globulin. These are the actual antibody infection fighters derived from the serum of numerous blood donors. The serum is first treated to kill off any infections the donors may have had and then the antibodies are harvested. Although these antibodies can be helpful against both bacterial and viral infections, in patients with latter we have seen a die off reaction (initial flaring of symptoms) with each injection of gamma globulin. I am now advising patients to start with the Nexavir first and add the gamma globulin 1-3 weeks later. I recommend 2 cc be given intramuscularly weekly or 4 cc IM every other week for 6 doses, and then as needed. Although it can also be given through an IV, this delivery method is very expensive and does not seem to bring any additional benefit.
Because Valcyte has been so effective and can eliminate the infection, I rarely prescribe the Nexavir anymore. The gamma globulin IM injections are wonderful in these illnesses, and a recent study suggested that they even help the nerve pain present in a third to half of those with fibromyalgia (though in that study they gave it IV). If your illness began with an infection, or persists despite other therapies, you may wish to discuss these treatments with your doctor
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