HHV6

 

Current NHS services show no interest in the role viral infection plays in ME/CFS.

We need the support of a central laboratory for testing ME/CFS patients’ blood. However, lead ME/CFS services are not interested in the role viral infection plays in the disease. As quoted from Professor Simon Wessely;

"We're not going to go doing more and more tests to find out what was the virus because, frankly, even if we found it there's nothing we're going to do about it. We're in the business of rehabilitation."
[1]

We do not believe that this approach is correct as a baseline for ME treatment. Our belief is that you cannot begin to rehabilitate until all co-infections and viruses have been identified and treated.

The following is taken from an excerpt from an interview with Dr Jacob Teitelbaum:

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.

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.

Let's look at chronic viral infections and how to approach them.

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.

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 CMV

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.

HHV-6 can persist in the brain tissue long after primary infection and after evidence of the virus has long disappeared from the plasma in the circulating blood.  Therefore, direct evidence of chronic infection is not easily attainable by standard laboratory tests. In other words, even though there is no DNA for HHV-6 (or other herpesviruses such as EBV) in the plasma, it is possible that one of more of these viruses are in fact smoldering in the tissues and throwing off inflammatory cytokines.

Elevated antibody titers can only suggest–not prove–that the virus is active. Short of a tissue biopsy, it may be impossible to find direct evidence of chronic HHV-6 infection. Therefore, physicians who suspect active virus, in a chronic case, must treat based on clinical judgment of the symptoms, using elevated antibodies as one of several “clues”. Infectious disease specialist Jose Montoya, MD from Stanford University did this with 12 patients, treated for long standing fatigue and elevated antibody titers to HHV-6 and EBV. He selected CFS patients who had both elevated titers and symptoms consistent with HHV-6 infection (including cognitive dysfunction) and then treated these patients with a strong antiviral (Valcyte). Nine of the twelve patients improved dramatically, some of whom had been sick for over 10 years (Kogelnik 2006). [2]

LINKS

http://phoenixrising.me/research-2/the-pathogens-in-chronic-fatigue-syndrome-mecfs/hhv-6-and-chronic-fatigue-syndrome-mecfs-an-overview

http://chronicfatigue.stanford.edu/infections/herpes.html

http://www.treatmentcenterforcfs.com/pdf/Dr.A.MartinLerner-Subset-directed-antiviral-treatment-of-142-herpesvirus-patients-with-CFS.pdf

 

 

 

 



[2] http://hhv-6foundation.org/associated-conditions/hhv-6-and-chronic-fatigue-syndrome

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