Page Synopsis: CFS is a broad diagnosis which encompasses diverse theorised pathogenesis, 'flare up' triggers etc. While it remains unclear whether CFS is due to infection, all CFS patients are shown to harbor infectious agents, and while some patients have been helped tremendously by antiviral and antibacterial treatments some even cured, many have not

Skill Level  4

Relevance:4 Technical Level:5

We don't know for certain how infection fits into the picture, though with the progress of Naviaux at Stanford labs we may soon have confirmation of his CDR theory


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                       Mycoplasma and Mycoplasma treatment (click to open) Following Dr Garth Nicolson's research into mycoplasma  M. fermentans, M. hominis, M. pneumoniae or M. genitalium  cfs, microencapsulated NADH  35 mg/d , l-carnitine  160 mg/d , membrane phospholipids  2000 mg/d , CoQ10  35 mg/d , α-ketoglutaric acid  180 mg/d , and other nutrients into an oral supplement  ATP FuelNTFactor EnergyLipids Powder soy lecithin extractNAD+ and Hydroinfused Hydrogen Rich Water Fom: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment' you have a Mycoplasma infection, macrolide and tetracycline classes of antibiotics  such as azithromycin and doxycycline  are effective treatments. For healthy people, two or three weeks treatment is required; longer treatment is usually needed in chronic illness like ME/CFS.1 Dr A Martin Lerner treats Mycoplasma pneumoniae infection in his ME/CFS patients with intravenous doxycycline 150 mg for six weeks, followed by oral doxycycline 100 to 150 mg twice daily or moxifloxacin 400 mg once daily for three months.1 Mycoplasma Roles in Disease + Treatment, Prevention - SelfHacked is treated with certain types of antibiotics. All species of Mycoplasma lack a cell wall and, therefore, they are not susceptible to penicillins and other antibiotics that act on this structure 166 Most antibiotics used in the treatment decrease Mycoplasmagrowth but do not kill the bacteria  bacteriostatic This is one of the reasons why eradicating Mycoplasmais often slow and depends on the efficacy of the host immune system. Macrolides, such as erythromycin, clarithromycin, and azithromycin are the treatment of choice for M. pneumoniaeinfections in both adults and children 4 ,28 ,167 Resistance to macrolides has been emerging and increasing in M. pneumoniaesince 2000, especially in Asia 168 ,169 Several Japanese studies have reported that 20 – 40% of strains are resistant to macrolides 153 ,168 Tetracyclines, fluoroquinolones  levofloxacin  and ketolides have also been effective in treating Mycoplasmainfection 4 ,170 ,167 In the past, tetracyclines have been effective against bothM. hominis and U. urealyticum, but resistance has developed. Clindamycin  is an alternative to the tetracyclines 171 Antibiotic therapy typically lasts 10-14 days. If your doctor prescribes a course of antibiotics, it is extremely important to finish the whole prescription, even if your symptoms disappear after the first few days.Failure to complete treatment may increase the risk of antibiotic resistance in the pathogen back to top of article to click to close                                                                                                                         click here to closeback to top of articleHuman herpes virus six  HHV-6 From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment' HHV-6 is found in nearly 100% of adults, usually in a latent inactive state. If you have an active HHV-6 infection, this may be contributing to or causing your symptoms, as active HHV-6 is linked to ME/CFS.1  2  There are two main variants of HHV-6: variant A and variant B, often denoted as HHV-6A and HHV-6B. Tests for HHV-6 do not usually distinguish between the two variants. This more neurotropic HHV-6A variant is more strongly linked to ME/CFS.1  2  So a positive test for HHV-6A may be quite significant if this virus is active. Dr Daniel Peterson found that 15% of ME/CFS patients have a HHV-6A infection in their cerebrospinal-fluid.1 Dr Kazuhiro Kondo has a theory that partial reactivation of HHV-6 may cause ME/CFS, as well as depression and bipolar disorder.1 From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment' Round Treatments, if waranted: If your tests indicate you have an active infection with HHV-6, Dr A. Martin Lerner has shown that the antiviral valganciclovir  Valcyte  450 mg three times daily is often beneficial.1 In Dr Lerner's study on 142 ME/CFS patients with herpes virus infections, 75% of patients responded to the appropriate antiviral treatment  Valtrex/Famvir for EBV, and/or Valcyte for HHV-6 and cytomegalovirus ; the average improvement in ME/CFS symptoms was a 2-point increase on the Energy Index Point Score  scale  for example, as a result of antiviral treatment, an average patient may go from level 4 to level 6 on this scale1 Professor Jose Montoya also found valganciclovir  Valcyte  450 mg twice daily effective when there is an active HHV-6 infection.1  It takes around 6 months before the benefits of Valcyte manifest. Note that Valcyte is potent antiviral drug with potentially serious side effects, and should only be taken under medical supervision. More info: Valcyte for CFS Valcyte is expensive: the cheapest price is around $7 for one 450 mg tablet. Professor Montoya also prescribes the anti-inflammatory colchicine and hydroxychloroquine which treats autoimmunity. More info on Lerner and Montoya's antiviral treatment for ME/CFS given in this post The antiviral Nexavir  formerly Kutapressin  displays potent in vitro activity against HHV-6,1  and this well-tolerated drug is used to treat ME/CFS. The antimalarial drug artesunate has efficacy against HHV-6.1 Dr Dan Peterson has had success using the antiviral cidofovir  Vistide  for ME/CFS patients with infections from the herpes family viruses HHV-6 and cytomegalovirus. Cidofovir is potent antiviral drug with potentially serious side effects, and should only be taken under medical supervision. More Info: Peterson Reports Cidofovir Effective in Treating Herpesvirus Infected ME/CFS Patients The HIV antiretroviral drug raltegravir  Isentress  is effective against cytomegalovirus, herpes simplex I virus,1 and may have efficacy against the whole family of herpesviruses.1 back to top of article to click to close                                                                                                                         click here to closeback to top of articleEBV From: The Autoimmune Virus? Groundbreaking EBV Finding Could Help Explain ME/CFS - Simmaron Research I sensed some awe in Ron Davis’s voice as he pushed for more understanding of Epstein-Barr Virus’s effects in ME/CFS during a talk at the Brain Science conference.  Davis is not to my knowledge finding much evidence of EBV reactivation in the severe ME/CFS patient study – a surprise – but he is very interested in what happened during that initial EBV infection, which appears to have triggered chronic fatigue syndrome  ME/CFS  in so many people. A large, complex and very common virus, EBV is responsible for infectious mononucleosis and appears to contribute to numerous autoimmune disorders. He’s not alone in his “admiration” for the virus. Simmaron’s Advisor, Dr. Daniel Peterson, whose clinical practice and research stemmed from an outbreak in the Lake Tahoe region of Chronic Fatigue Syndrome, has tracked EBV in patients for decades, noting very high titers to EBV and other herpes viruses in subsets of patients. It’s not surprising that these two important figures have had their eyes on EBV. EBV, after all, is kind of in a league of its own.  An invader of B and epithelial cells, the 50th anniversary of its discovery was recently celebrated with numerous reviews.  Epstein-Barr was discovered in 1966 by Anthony Epstein and Yvonne Barr. It was the first human virus shown to cause cancer The sequencing of its large genome in 1995 helped launch the genomic era. One of the more massive and complicated viruses, it’s one of the very few viruses that’s able to avoid elimination: once EBV infects your B-cells, it’s in your body to stay. It’s able to effectively hide from the immune system and reactivate just enough so that when the infected B-cells die it can move on to other cells. We’re well equipped to ward off EBV when we’re young – it usually produces only minor symptoms – but as our immune systems alter as we age, that changes.  Encountering EBV as an adolescent or adult  infectious mononucleosis, glandular fever   – as increasingly happens in our germ phobic age – often means months of convalescence as our immune systems struggle to ward off this powerful virus. The problems don’t stop there. We know that infectious mononucleosis  IM  is a common trigger of ME/CFS but coming down with IM/glandular fever  in adolescence has also been shown to increase one’s risk of coming down with multiple sclerosis 2-4 fold and lupus by fifty percent.  Because of EBV’s ability to remain latent in the body, EBV reactivations are a huge problem for transplant patients  with compromised immune systems. The big question concerning EBV is how a virus which has essentially been latent for decades could contribute to serious diseases like MS and lupus. We now may have the answer. Last week, what will probably turn out to be a seminal paper in pathogen research directly showed for the first time how EBV appears to be able to trigger autoimmune diseases later in life and could conceivably play a role in ME/CFS. The rather hum drum title of the paper “Transcription factors operate across disease loci with EBNA2 implicated in autoimmunity” in the Nature Genetics Journal hardly hinted at the possibilities the paper presents. Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity ttps:// John B. Harley , Xiaoting Chen , Mario Pujato , Daniel Miller , Avery Maddox , Carmy Forney , Albert F. Magnusen , Arthur Lynch , Kashish Chetal , Masashi Yukawa , Artem Barski , Nathan Salomonis , Kenneth M. Kaufman , Leah C. Kottyan  & Matthew T. Weirauch Nature Genetics  2018  doi:10.1038/s41588-018-0102-3 EBV  consists of several proteins of which EBNA-2 is one. EBNA-2 is EBV’s main viral transactivator ; i.e. it’s a transcription factor that turns on genes in an infected cell that help EBV to survive. Essentially EBNA-2 allows EBV to hijack a cell’s genetics and put them to its own use. The study – produced by researchers at Cinncinnati’s Children Hospital – demonstrated that once EBV infects B-cells, it turns on genes that have been identified as risk factors for a boatload of autoimmune diseases. It turns out that even though the virus is, so to speak, latent; i.e. it’s not replicating – its transcription factor is still active  – altering the expression of our genes. The genes that it affects just happen to be the same genes that increase the risk of developing lupus, multiple sclerosis  MS , rheumatoid arthritis  RA , juvenile idiopathic arthritis  JIA , inflammatory bowel disease  IBD , celiac disease, and type 1 diabetes.  Apparently decades of genetic assault from EBV’s transcription factor can set the stage or at least contribute to many autoimmune diseases.!IFrame Content Chronic diseases are usually caused by a variety of genetic and environmental factors. Because not everyone with these transcription factors comes down with a chronic illness, other factors must play a role. The authors believe, though, that the gene expression changes induced by the virus in the B cells could account for a large number of people with lupus and MS who fall ill.  Chronic Fatigue Syndrome and EBV/Infectious Mononucleosis – A Short History Researchers have been trying to figure out – mostly unsuccessfully\- what the heck happens to plunge people with infectious mononucleosis into ME/CFS for quite some time. Infectious mononucleosis/glandular fever is believed to be a common trigger of ME/CFS In fact, infectious mononucleosis/glandular fever was probably the first disease associated with ME/CFS. Studies in the mid-1990’s, including one from the CDC, suggested ME/CFS was, at least in part,  “chronic infectious mononucleosis ” or “chronic mononucleosis syndrome “.  Even Stephen Straus penned a paper on the “The chronic mononucleosis syndrome “. Straus’s small 1989 study reporting high rates of psychiatric diagnoses in ME/CFS patients prior to their becoming ill set a theme in motion which was disproved by two Peter White  ME/CFS IM  publications.  White found IM/glandular fever to be a particularly strong trigger of ME/CFS  which he concluded was probably responsible for about 3,000 new cases of ME/CFS a year in the U.K. A 1992 Swedish study began a trend of examining people with ME/CFS during infectious mononucleosis and afterwards in order to try and determine what happened. That study concluded that whatever happened was not due to EBV reactivation In 2010 Taylor found reduced peak oxygen consumption  during exercise in adolescents with ME/CFS after IM compared to IM patients who had recovered. Broderick’s finding of altered cytokine networks  associated with Th17 in ME/CFS patients following IM suggested immune dysregulation had occurred. Glaser’s 2005 study suggested that an EBV encoded enzyme  produced by a non-replicating form of EBV could be producing symptoms in ME/CFS.  Lerner’s 2012 study suggested that antibodies to two EBV produced proteins were commonly present in ME/CFS – suggesting that a prolonged immune reaction to EBV  might be occurring in ME/CFS as well. In 2014 Loebel/Scheibenbogen suggested that ME/CFS patients may be having difficulty controlling the early stages of EBV reactivation   Loebel’s 2017 follow up study suggested that ME/CFS patients’ immune system might be over-reacting to an EBV produced protein and that autoimmunity might be involved. Leonard Jason’s large IM college student study will hopefully provide clues why some people never recover from it. He’s completing data analysis of a study examining college students who came down with infectious mononucleosis and then ME/CFS. So far Jason has found that at least 4-5% of college students come down with IM while at school. rTreatment Implications Interestingly, several drugs that are available can block some of the transcription factors EBV has inserted into B-cells.   I was unable to determine what they are  The authors also hope the study will help spur more efforts to produce an EBV vaccine. Next For ME/CFS and EBV Now that we have evidence that EBV/IM contributes to many autoimmune diseases, it’s hard to think that ME/CFS is not somehow involved. Chronic fatigue syndrome is different in that infectious mononucleosis  and other infections  immediately triggers ME/CFS in many people. What we don’t know is if bouts of IM also trigger ME/CFS 5, 10, 15 or more years later as occurs in these other disorders. Opportunities for Collaboration Open Up The big question awaiting ME/CFS now is if the abnormal transcription factors associated with the autoimmune diseases in the recent paper are present. The good news is that a study determining that appears to be within reach of an ME/CFS researcher with the technical ability and funds. In an unusual move, the Cincinnati researchers are making the computer code they used available to other researchers.  “We are going to great lengths to not only make the computer code available, but all of the data and all of the results. We think it’s an interesting approach that could have implications for many diseases, so we’re contacting experts on the various diseases and sharing the results and seeing if they want to collaborate to follow-up on them.” Weinrauch “This discovery is probably fundamental enough that it will spur many other scientists around the world to reconsider this virus in these disorders” Harley They believe EBV will be implicated in many more diseases, and there is already some evidence that it is.  Using the same analytical techniques, they’ve already identified 94 other diseases including many non-autoimmune diseases in which EBV may play a role. This is one of the few studies in which the researchers are so jazzed by their results that they’ve dropped all pretenses to modesty. The study results need to be validated, but because EBV is so common and is potentially linked to so many autoimmune  and other diseases , it has the potential to rewrite our understanding of how autoimmune diseases arise. The authors fully recognize the potential importance of their finding. The lead author of the study, John Harley, said:  “I’ve been a co-author in almost 500 papers. This one is more important than all of the rest put together. It is a capstone to a career in medical research,” Harley One of the senior authors of the study stated: “This same cast of characters is a villain in multiple immune-related diseases. They’re playing that role through different ways, and doing it at different places in your genome, but it’s the same sinister characters. So if we could develop therapies to stop them from doing this, then it would help multiple diseases.” Matthew Weirauch From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment' is a high 95% prevalence of Epstein-Barr virus in the adult population, so most people will have this virus in their system, but usually in a latent inactive state. However, if you have an active EBV infection, it is possible this may be contributing to or causing your ME/CFS symptoms. After mononucleosis  glandular fever , which is mostly caused by EBV, ME/CFS was found as a sequelae in 9% of cases.1  Another study found that at 6, 12 and 24 months after mononucleosis, 13%, 7% and 4% of patients respectively met the criteria for CFS, indicating that post-mononucleosis CFS can clear up over time, to an extent.1 Evidence indicates that some subtypes of ME/CFS may be due to partial reactivation of Epstein-Barr virus.1  2 The Epstein Barr Virus  EBV , which causes mononucleosis  also called glandular fever , has been continually linked with Chronic Fatigue and Fibromyalgia  FM Many people with these conditions initially had EBV and never recovered. Recent studies continue to associate the two together. Other viruses are also commonly found in the blood of many people with CFS and FM. People with these conditions, regularly test positive for elevated levels of RNase L, which is an enzyme found in the cells of the body. It is activated when the body is under attack from viruses. However it appears that the RNase L system of those with CFS is compromised, and is therefore unable to effectively fight the viruses. From: 'Epstein-Barr Virus Evidence for Role in Chronic Fatigue Syndrome' The Epstein-Barr virus  EBV  is a member of the herpesvirus family and one of the most common human viruses. The Epstein-Barr virus  EBV  has long been tentatively connected to chronic fatigue syndrome  ME/CFS.  Some researchers say it's an important causal factor while others say it's not involved with this disease. Those who believe it is connected often talk about reactivation. EBV is in the herpesvirus family. All herpesviruses stay in your system forever, but generally remain dormant most of the time. When they do become active, specialized cells in the immune system, including B-cells and T-cells, typically don't have a problem knocking them back down again. Most people aren't even aware that this process is going on. That's because B\- and T-cells, in a healthy immune system, remember the virus and can rapidly assemble an army of antibodies to keep it in check. If the immune system isn't working correctly, though, it could theoretically allow the virus to gain a foothold at levels that once again make you sick. That's called reactivation. Evidence of Reactivation Research published in 2014 shores up the hypothesis of EBV reactivation as a possible cause of some cases of ME/CFS. In this study, scientists found evidence that the B\- and T-cells of many people with this disease were unable to remember EBV, meaning a reactivated virus would be better able to thrive, reproduce, and cause symptoms. Researchers found this impaired cellular memory in the immune systems of 76 percent of the more than 400 study participants. That's an impressive percentage. Along with showing what may cause and sustain some cases of ME/CFS, researchers say this work could lead to a long-sought diagnostic marker. More About the Epstein-Barr Virus EBV is a nasty bug. It's best known for causing infectious mononucleosis, called mono or the "kissing disease." Symptoms of mono include: severe fatigue sore throat headache fever muscle aches swollen lymph nodes sensitivity to light shortness of breath Recovery from mono is known to take a long time, and recurrences are marked by extreme fatigue. Some researchers have long believed it's no coincidence that those are also symptoms of ME/CFS. However, a large portion of the population carries EBV and only a small number of those people develop ME/CFS. That has confounded attempts to explain how EBV could contribute to the illness. This study appears to overcome that problem, though, providing an answer to that question. It doesn't answer questions about why some people's immune systems seem to be blind to this particular virus, though. That's a topic for future research. Previous Studies Other studies have shown that a significant number of juvenile ME/CFS cases followed mono, and many adolescents whom doctors deem unrecovered from mono fit the ME/CFS diagnostic criteria. It seems that the harder EBV hits, the more likely it is to cause prolonged illness.  Read more about these findings from Cort Johnson at Health Rising. In addition to mono, EBV is linked to certain types of cancer, which could explain the higher incidence of cancer-related illness and death some ME/CFS experts have observed. EBV may also play a role in multiple sclerosis. Some research also suggests it can mimic acute leukemia. With this new discovery of impaired cellular memory, we may have filled a significant gap in knowledge about how EBV could be triggering ME/CFS and contributing to on-going symptoms. While more work is needed to verify this study, it could prompt more doctors to prescribe anti-viral medications  such as valacyclovir or valganciclovir  for ME/CFS patients with high EBV levels. Sources: Chhabra P, Law AD, Sharma U, et al. Epstein-barr virus infection masquerading as acute leukemia: a report of two cases and review of literature. Indian journal of hematology & blood transfusion. 2014 Mar;30 1 :26-8. Loebel M, Strohschein K, Giannini C, et al. Deficient EBV-specific B\- and T-cell response in patients with chronic fatigue syndrome. PLoS One. 2014 Jan 15;9 1 :e85387. eCollection 2014. From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment' 1st Round Treatments, if waranted:If your tests indicate you have an active infection with EBV, this may be causing or contributing to your ME/CFS symptoms. Dr A. Martin Lerner has shown that the antiviral drug valacyclovir Valtrex  at a dose of 1,000 mg four times daily often improves ME/CFS symptoms, though usually the benefits only begin to become noticeable after around 3.5 months of treatment.1  The full improvements from this drug appear after 2 years of treatment.1  Those who experience side effects from valacyclovir can substitute with famciclovir  Famvir  at the same dosage; Famvir is usually much better tolerated. In Dr Lerner's study on 142 ME/CFS patients with herpes virus infections, 75% of patients responded to the appropriate antiviral treatment  Valtrex/Famvir for EBV, and/or Valcyte for HHV-6 and cytomegalovirus ; the average improvement in ME/CFS symptoms was a 2-point increase on the Energy Index Point Score  scale  for example, as a result of antiviral treatment, an average patient may go from level 4 to level 6 on this scale1 Professor Jose Montoya has found valganciclovir  Valcyte  effective when there is an active EBV infection. This drug needs to be taken for 6 month in order to see improvements.1  Valcyte can have serious side effects and thus patients taking it must be medically monitored. More info on Lerner and Montoya's antiviral treatment for ME/CFS given in this post Dr Jay Goldstein used the H2 antihistamine cimetidine Tagamet  300 mg three times daily as an off-label treatment for mononucleosis.1  2  The H2 antihistamine ranitidine Zantac , which is available over the counter without prescription, can be used in place of cimetidine. The antiviral Nexavir  formerly Kutapressin  may have some activity against Epstein-Barr virus.1 From: 'Herpesvirus Infections of the Nervous System' primary infection, the virus becomes latent in ganglia or lymphoid tissue.  How remove? back to top of article to click to close                                                                                                                         click here to closeback to top of articleEnterovirus Enteroviruses in chronic fatigue syndrome: “now you see them, now you don’t” | Journal of Neurology, Neurosurgery & Psychiatry The reverse transcription– polymerase chain reaction (RT PCR) technique is widely applied to test for the presence of enterovirus genomes and is the method of choice for identifying virus infection in many countries. This technique is very sensitive and specific, particularly in diagnosing CNS infections from cerebrospinal fluid specimens, and has become the ‘gold standard’ of diagnosis, surpassing viral culture. Enterovirus RNAs have also been detected in myocardial biopsies from patients with myocarditis and dilated cardiomyopathy, in muscle of people with inflammatory muscle disease and chronic fatigue syndrome, and in brain biopsies. The significance of these findings is not clear, as infectious virus can rarely be isolated and viral antigen cannot be detected. Highly conserved sequences of the 5′ end of enterovirus genomes have allowed the design of PCR primers detecting most enterovirus RNAs.  As the EV22 genome is very different from that of the other enteroviruses (see earlier), tailor made primers have to be added in a multiplex RT PCR to include detection of these viruses, which cause infections particularly in neonates and infants. A modified RT PCR procedure can differentiate between wild type and vaccine derived poliovirus infections. Modern sequencing techniques (Deep, Massive parallel or Next Generation sequencing) offer the possibility of sequencing without either cell culture isolation, PCR or knowledge of the sequence to be sought and are having a major impact on diagnosis of enterovirus and other infections, and environmental surveillance. Epidemiology of enterovirus infectionsEnteroviruses are mainly transmitted by the face oral route, due to the fact that viruses are shed in faeces for weeks or months after infection.  Spread is particularly intense within families, usually starting from the primary infection of young children. In temperate climates, there are seasonal peaks (July– September in the northern hemisphere and December– February in the southern hemisphere), whereas in subtropical and tropical climates enterovirus infections occur all the year round.  Most primary human enterovirus infections occur during the first decade of life. Type- specific surveillance in several geographical regions has shown that coxsackieviruses A9, A16, P and B4 and echovirus types 6, 9, 11, 19, 22, and 30 are most frequently found. Prevention of enterovirus infections as there are only three poliovirus types and no significant animal reservoir, it has been possible to develop very successful poliovirus vaccines.  In 1954, a formalin- inactivated poliovirus vaccine (IPV) was introduced by Dr Jonas Salk in the United States of America, and in 1962 Dr Albert Sabin introduced a vaccine consisting of live- attenuated strains of the three poliovirus types which could be given orally (OPV).  Protection by the live- attenuated vaccine is affected mainly at the site of entry by eliciting locally virus- specific Ignas and Giggs. Inactivated vaccine mainly elicits serum IgGs which prevent infection of the CNS and other sites distant of the port of entry by neutralization of viraemic virus List of enterovirus infection studies - MEpedia Enterovirus: What Parents Need to Know - AFM virus: The new polio-like disease affecting kids, explained AFM: What We Know About This Paralyzing Illness - The Mysterious Polio-Like Disease Affecting American Kids - The Atlantic Frontiers | Salivary DNA Loads for Human Herpesviruses 6 and 7 Are Correlated With Disease Phenotype in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | Medicine Enteroviruses and the Chronic Fatigue Syndrome | Clinical Infectious Diseases | Oxford Academic Did The ME/CFS Field Give Up Too Early on Enteroviruses? - Health Rising Enteroviruses in chronic fatigue syndrome: “now you see them, now you don’t” | Journal of Neurology, Neurosurgery & Psychiatry List of enterovirus infection studies - MEpedia Enterovirus: What Parents Need to Know - AFM virus: The new polio-like disease affecting kids, explained AFM virus: The new polio-like disease affecting kids, explained AFM: What We Know About This Paralyzing Illness - The Mysterious Polio-Like Disease Affecting American Kids - The Atlantic back to top of article to click to close                                                                                                                         click here to closeback to top of article



  • 52% of CFS patients had active mycoplamsa infection,


  • 30.5% had active HHV-6 infection,


  • And 7.5% had Chlamydia pneumoniae infections,


  • Versus only 6%, 9% and 1% of controls, respectively


“Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of Chronic Fatigue Syndrome Patients: Association with Signs and Symptoms”

Please also see The vagus nerve infection hypothesis which "contends that CFS symptoms are a pathologically exaggerated version of normal sickness behavior that can occur when sensory vagal ganglia structures containing a number of nerve cell bodies or paraganglia non-nerve cells that surround nerves are themselves infected with any virus or bacteria.... The glial cells cells that support and protect neurons can bombard the sensory vagus nerve with proinflammatory cytokines and other neuroexcitatory substances, initiating an exaggerated and intractable sickness behavior signal. According to this hypothesis, any pathogenic infection of the vagus nerve can cause CFS, which resolves the ongoing controversy about finding a single pathogen." The neuroimmune cells whose job is to protect the nerve, such as mast cells and glial cells, can sense an infectious agent and become activated, in turn signaling the vagus nerve to tell the brain there is an infection present, causing a systemic reaction.1


VanElzakker believes that any infectious agent with an affinity for nerve tissues can cause a vagus nerve infection, including HHV-6, Epstein-Barr virus, Varicella zoster virus, chickenpox, certain kinds of enteroviruses and even borrelia, the bacterium that causes Lyme disease. He thinks this could explain why no single infective agent has been isolated as the cause of CFS, even though all of these agents have been associated with CFS


The vagus nerve, also called the tenth cranial nerve, starts in the brain and runs down the trunk of the body, with branches that innervate all of the major organs.2 It is responsible for the sickness response, an involuntary response characterized by fatigue, fever, myalgia, depression, and other symptoms that are often observed in patients with CFS"


                         Dr. Holtorf on Infectious Causes of ME/CFS and Fibromyalgia (click to open)Infectious Causes of ME/CFS and FM Numerous studies have demonstrated a high incidence of chronic infections in chronic fatigue syndrome and fibromyalgia. These include viral infections of Epstein-barr (EBV), cytomegalovirus (CMV), human herpes virus-6, (HHV-6), and bacterial infections such as mycoplasma, Chlamydia pneumoniae (CP) and Borrelia burgdorferi (Lyme disease). There is controversy regarding the presence of active infection in these conditions because physicians, including infectious disease specialists, do not understand that the standard way to diagnose acute infections – an elevation of IgG and IgM antibodies – is not a sensitive means of detecting chronic infections in these patients (1-21). With an acute [new] infection, the body will start producing IgM antibodies against that infection and then start producing IgG antibodies after a few weeks so there is an elevation of both IgG and IgM antibodies. Chronic reactivating infections, such as those mentioned above, do not stimulate IgM antibodies, as they are not new infections but rather intracellular reactivating infections. So most doctors, again including infectious disease specialists, will tell patients who have elevated IgG antibodies that they had an old infection or previous exposure and that there is no evidence of, or they do not have, an active infection – because that is what they learned in medical school. This standard way of detecting active infections has clearly been shown to be inaccurate and misses the overwhelming majority of patients with active infections (1-21). Polymerase chain reaction (PCR) testing [which can generate thousands of copies of a DNA sequence from one or a few copies] is much more sensitive in a research setting than in the clinical setting, because if the blood sits for more than a few hours, the infectious organism’s DNA degrades and often goes undetected. So in a clinical setting, PCR is a specific test (if it is positive you know you have an active infection), but suffers from low sensitivity (often negative despite an active chronic infection). Additionally limiting sensitivity is the fact these infections are not concentrated in the blood or serum but rather in the tissues, especially nerves, brain and the white blood cells. Physicians must have a high incidence of suspicion and look for elevated IgG or early antigen (EA) antibodies along with other signs of chronic infections including low natural killer cell activity, high RNase-L activity, high ACE (> 35), coagulation activation, high tumor necrosis factor (TNF), low melanocyte stimulation hormone (MSH), high interleukin-6 (IL-6), low WBC [white blood cell levels], increased 1,25 vitamin D/25 vitamin D ratio, and elevated or decreased total IgA, IgM or IgG levels. Chronic infections are almost always present in: • Those whose symptoms started very acutely, especially with an infection, • Those whose symptoms were ever associated with swollen lymph nodes or sore throat, • And those with significant cognitive dysfunction or flu-like symptoms. It must be remembered that in order to have the highest probability of successful treatment, a multi-system approach should be initiated. (See Dr. Holtorf’s handout, “New Standard for the Treatment of Chronic Fatigue Syndrome and Fibromyalgia.”). HERPES VIRUSES (Epstein-Barr, Cytomegalovirus and HHV-6) EBV, CMV and HHV-6 cause or contribute to the symptoms of a large percentage of CFS and FM patients. As stated previously, the presence of active infections correlates with an elevated IgG antibody, despite the lack of IgM antibodies (10-21). These infections are generally not acute, but rather intracellular reactivation of an old infection. An elevation of IgM antibodies is typically not seen with active infections of EBV, CMV, HHV-6 (10-21). Due to the immune dysfunction seen in CFS, in addition to a lack of IgM antibody formation, there may also be a lack of IgG antibodies present despite the presence of an active infection in CFS patients(22,17,23). This has also been demonstrated to be the case with AIDS patients, as demonstrated in the study published in the New England Journal of Medicine entitled “Absence of detectable IgM antibodies during cytomegalovirus disease in patients with AIDS”(22). It has also been shown that the presence of anti-thyroid antibodies in CFS patients has a significant correlation with active HHV-6 infection (24). » A study published in Acta Pathologica, Microbiologica et Immunologica Scandinavica entitled “Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of Chronic Fatigue Syndrome Patients: Association with Signs and Symptoms” found: • 52% of CFS patients had active mycoplamsa infection, • 30.5% had active HHV-6 infection, • And 7.5% had Chlamydia pneumoniae infections, • Versus only 6%, 9% and 1% of controls, 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 (25).” » A study entitled “A Chronic Illness Characterized by Fatigue, Neurological and Immunological Disorders, and Active Human Herpes virus Type 6 Infection” published in the Annals of Internal Medicine found 70% of patients with CFS had active HHV-6 infection through the use of primary cell cultures and confirmation using assays of monoclonal antibodies specific for HHV-6 proteins and by PCR. Again, an elevation of IgM antibodies is generally not seen (26). As summarized below, when specialized testing is used to detect active vs. past infection of HHV-6, the overwhelming number of studies demonstrate a high incidence of active herpes virus infections. These reactivation infections often do not illicit an IgG and especially not an IgM response, so standard serologic testing is specific but not sensitive for such infections. As mentioned before, PCR testing in a research setting is much more reliable, sensitive and useful than in the clinical setting when the blood is usually not processed for 12 to 48 hours. » Wagner et al, found that 61% of CFS patients who had elevated IgG antibodies, and 81% with immune deficiency, had confirmed active HHV-6 infection, vs. only 19% of those patients who did not(15). This is regardless of whether or not IgM antibodies were elevated. Below in Figure 1 is a summary of studies that have looked at the incidence of active HHV-6 infection in CFS/FM patients vs. controls, with 83% of the studies demonstrating a large portion of CFS/FM patients have an active HHV-6 infection. Figure 1 Assays that differentiated between active and latent virus: 83% positive(click image to enlarge)» A study by Lerner [A. Martin Lerner at the Treatment Center for CFS] found that treating patients with 6 months of Valtrex resulted in a significant improvement in symptoms (46). » In a separate study, Lerner et al found that in CFS patients with elevated IgG antibody against CMV, treatment with the intravenous antiviral ganciclovir, which has a more broad spectrum coverage than Valtrex and anti-CMV activity, resulted in 72% of patients returning to their premorbid health states (total resolution of symptoms) (47). » A randomized, placebo controlled study published in Clinical Infectious Diseases demonstrated that in CFS patients with elevated IgG antibodies against CMV, a combination of oral Valtrex and intravenous ganciclovir resulted in dramatic improvements with almost complete resolution of symptoms (27). » Montoya et al. at Stanford University [Infectious Disease Clinic] treated chronic fatigue syndrome patients with 6 months of valganciclovir (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. Nine of the twelve treated patients (75%) “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 and HHV-6 IgG titers significantly dropped. (21) » Lerner et al collected data on 142 CFS patients treated with antivirals. They found that long-term antiviral therapy was effective unless other untreated coinfections were present.(53) » We [Holtorf Medical Group] have found that an effective treatment protocol requires the use of an anti-infectious treatment in a significant portion of CFS patients (and the majority of severely affected). While no single treatment is universally beneficial, we have found that a variety of anti-infectious and immune-modulatory therapies can be very effective. These include Valcyte, Isoprinosine, Kutapressin, gamma globulin (IM or IV), antiviral nutraceuticals, species specific transfer factor, antibiotics, anti-retrovirals, anti-parasitics and low dose naltrexone. There are a number of markers that indicate that there is an underlying chronic infection as a cause or contributor to the illness. These include: • Flu-like symptoms or symptoms started with a flu-like illness; • Elevated IgG or EA against Epstein-Barr virus, Cytomegalovirus and/or HHV-6; • Low Natural Killer cell activity or number; • High reverse T3 or low free T3/reverse T3 ratio; • Low CD57; • High eosinophilic cationic protein (ECP) or vascular endothelial growth factor (VEGF); • High RNase-L activity; • High ACE (> 35); • Coagulation activation (high D-dimer, thrombin-prothombin complex, high prothrombin fragment 1 & 2, PAI-1 or soluble fragment monomer); • High tumor necrosis factor (TNF), IL-6 or NFKB; • Low melanocyte stimulation hormone (MSH); • Low WBC; • Increased 1,25 vitamin D/25 vitamin D ratio; • High C4a or C3a; • And/or elevated or decreased IgA, IgM or IgG levels; • Positive XMRV antibody or culture test. This study contributes more confirmatory evidence that IgM antibodies are not typically elevated in chronic reactivating infections, so most patients are incorrectly told they do not have an active infection based on such testing. This study also demonstrated the lack of sensitivity of standard PCR testing. There is also evidence that CFS may be due to the above discussed infections with “stealth adaptation” (28-38). This is primarily due to the deletion of the genes coding for the major antigenic components normally targeted by the cellular immune system. “Stealth viral adaptation” results in replication that is less efficient than conventional viruses, but has a distinct advantage over conventional viruses in not having to confront the body’s cellular immune defense mechanisms. The virus can, therefore, evade the immune system and create persistent ongoing infections in spite of an individual’s intact immune system (28-38). A number of studies have also shown dramatic improvement in patients with interferon treatments, especially those with low Natural Killer cell function (39,40,41). While ganciclovir and interferon may be effective, their toxicity precludes their use and there are less toxic means of eradicating these infections. MYCOPLASMA Numerous studies have demonstrated a high incidence of active Mycoplasma infection in CFS and FM (1,44-52). [Mycoplasma are unique fungus-like bacteria that lack a cell wall and aren’t affected by many common antibiotics that keep bacteria from multiplying by interfering with their cell wall formation.] » Nijs et al. published a study in the journal Immunology and Medical Microbiology entitled “High Prevalence of Mycoplasma Infections Among European Chronic Fatigue Syndrome Patients,” which demonstrated that 68% of CFS patients had an active mycoplasma infection as diagnosed with specialized polymerase chain reaction (PCR) testing where the red and white cells were immediately lysed and centrifuged to concentrate and collect the DNA (1). Being predominantly intracellular, there is typically not a significant serologic antibody response or just an isolated IgG response with this number of other intracellular infections, so IgG and especially IgM antibodies are almost always in the normal range despite the presence of an active infection (1-9). This study and others discussed below demonstrated that IGM antibodies are not helpful in the diagnosis of an active infection in CFS and FM. Nijs et al. stated, “Mycoplasma detection based on antibody testing is characterized by a very high specificity [if IGG and IGM positive], but extremely low sensitivity [active infection almost always present without elevated IgG and IgM an¬tibodies] renders it useless as a diagnostic tool (1).” » A study by Dylewski et al. in the New England Journal of Medicine demonstrates that in immune compromised patients, such as this patient, 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 (9). » A study entitled “Diagnosis and Treatment of Chronic Mycoplasmal Infections in Fibromyalgia and Chronic Fatigue Syndrome: Relationship to Gulf War Illness,” published in Biomedical Therapy investigated the presence of active mycoplasmal infection by forensic PCR in patients with CFS and/or FM vs. controls. They found that 63% of CFS/FM patients had active mycoplasmal species infection compared to 9% of normals, and more specifically the incidence of active Mycoplasma fermentans infection was 50% in CFS/FM patients vs. 0% of controls (2). » A study published in the International Journal of Medicine Biology Environment tested the blood of 565 CFS and/or FM patients vs. 71 healthy controls. They found 53.1% of patients were positive for mycoplasmal infection vs. only 7 out of 71 controls – and 24.6% of patients had an M. fermentans infection, vs. 2.8% of normals (42). » A study published in the International Journal of Occupational Medicine, Immunology and Toxicology found that through specialized testing: • More than half of Gulf War Syndrome/CFS patients had active mycoplasma infections that would not have been detected by standard serological IgG and IgM testing, • And that 78% of the patients completely recovered with appropriate treatment. • Additionally, all of recovered patients who were subsequently retested no longer had evidence of infection (7). » A study and review published in the Antimicrobics and Infectious Disease Newsletter discussed the high incidence of mycoplasma infections in CFS. • They discuss the fact that the culturing procedures and serological testing are insensitive for detecting intracellular infections due to the fact that there is usually a lack of hormonal response with these infections resulting in “normal” antibody titers or an isolated elevation of IgG antibodies with a lack of IgM antibodies (8). • Sophisticated PCR testing found multiple species of mycoplasma in the majority of CFS patients. • They found of the 87 Gulf War illness-chronic fatigue syndrome patients treated with antibiotics, most relapsed after the first 6 week trial and most felt worse, but after up to 6 cycles of 6 weeks of therapy approximately 80% of these patients recovered and were able to return to their normal functional capacity. This was not a placebo controlled trial, but they discuss the fact that it is unlikely a placebo effect that most patients felt worse during treatment. They conclude stating that in order to be successful in the treatment of Gulf War Illness-chronic fatigue syndrome, a comprehensive treatment approach must be used that addresses the numerous physiological abnormalities, including chronic infections (8). » A study by Nasralla et al. published in the European Journal of Clinical Microbiology & Infectious Disease entitled “Multiple Mycoplasmal Infections Detected in Blood of Chronic Fatigue Syndrome and Fibromyalgia Syndrome Patients” investigated the presence of different mycoplasmal species in blood samples from mycoplasma positive patients with chronic fatigue syndrome and/or Fibromyalgia. They found that the majority of patients had multiple species of mycoplasmal infections, with: • 59% of patients having active M. pneumoniae infections, • 48% having active M. fermentans infection, • 31% having an active M. hominis, • And 20% having M. penetrans (43). XMRV (Xenotropic Murine Leukemia Virus-Related Virus) I was skeptical about XMRV at first and thought it was most likely an opportunistic infection. One reason was that Quest did a pilot study in our office and we found that all the patients who were positive were the chronic Lyme patients. [Quest Diagnostics Clinical Trials in Valencia, CA – See their poster, “A Sensitive Real-time Assay for the Detection and Quantification of XMRV,” presented at the recent 2011 Conference on Retroviruses and Opportunistic Infections in Boston.] Thus my thinking was that Lyme must the primary infection with XMRV being secondary or opportunistic. Now I think that was too simplistic and think the evidence is showing that having XMRV is a reason that Lyme may not be cleared in some or many patients and may need to be treated. Our initial treatment with anti-retrovirals has been encouraging. I have been using Isentress [raltegravir] and then adding Viread [tenofovir]. Also using GcMAF [“vitamin D-binding protein,” thought to activate immune macrophage response to infectious micro-organisms] in some. [ProHealth note: As a means of sharing the findings of these anti-retroviral treatments, Dr. Holtorf has indicated he will construct a brief Q&A with one or more of the chronic Lyme patients in his care who may wish to volunteer their experience and observations regarding the therapy. To be included in a future newsletter.] _____ References 1. Jo Nijs J et al. High prevalence of Mycoplasma infections among European chronic fatigue syndrome patients. Examination of four Mycoplasma species in blood of chronic fatigue syndrome patients. FEMS Immunology and Medical Microbiology. Volume 34, Issue 3, 15 November 2002, Pages 209-214. 2. Garth L. Nicolson, Marwan Nasralla, Joerg Haier and Nancy L. Nicolson. Diagnosis and Treatment of Chronic Mycoplasmal Infections in Fibromyalgia and Chronic Fatigue Syndromes: Relationship to Gulf War Illness. Biomed. Therapy 1998; 16: 266-271 3. Baseman JB, Tully JG. Mycoplasmas: Sophisticated, reemerging, and burdened by their Notoriety. Emerg Infect Dis 1997 (3): 21-32. 4. Lo S-C, Dawson MS, Newton PB III. Association of the virus-like infectious agent originally reported in patients with AIDS with acute fatal disease in previously healthy non-AIDS patients. Am J Trop Med Hyg 1989 (40): 399-409. 5. Lo SC, Wear DJ, Shih WK, Wang RYH, Newton PB, Rodriguez JF. Fatal systemic infections of non-human primates by Mycoplasma fermentans (incognitus strain). Clin Infect Dis 1993 (17) (Suppl 1): S283-288. 6. Lo SC, Buchholz CL, Wear DJ, Hohm RC, Marty AM. Histopathology and doxycycline treatment in a previously healthy non-AIDS patient systemically infected by Mycoplasma fermentans (incognitus strain). Mod Pathol 1991 (6): 750-754. 7. Nicolson G, Nicolson N. diagnosis and treatment of Mycoplamal Infections in Persian Gulf War Illness-CFIDS Patients. International Journal of Occupational Medicine, Immunology and Toxicology 1996;5:69-78. 8. Nasrala M et al. The Pathogenesis and Treatment of Mycoplasmal Infections. Antimicrobics and Infectious Disease Newsletter 1999;17(!!);81-88 9. Dylewski J et al. Absence of detectable IgM antibody during cytomegalovirus disease in patients with AIDS. New England Journal of Medicine 1985:309:493. 10. Carruthers et al. Myalgic Encepalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome.Vol 11(1) 2003. 11. Ablashi DV, Zompetta C, Lease C, Josephs SF, Balachandran N, Komaroff AL, Krueger GRF, Henry B, Luka J and Salahuddin SZ. Human herpesvirus-6 (HHV-6) and chronic fatigue syndrome (CFS). Canada Disease Weekly Report 1991; 175E:33-40. 12. Zorenzenon M, Rukh G Botta GA et al. Active HHV-6 infection in chronic fatigue syndrome patients from Italy: New data. J Chron Fatigue Syndr 1996;2(4):3-12. 13. Knox KK, Brewer JH, and Carrigan DR. Persistent active human herpesvirus six (HHV-6) infections in patients with chronic fatigue syndrome. J Chron Fatigue Syndr 1999;5:245-246. 14. Brewer JH, Know KK and Carrigan DR. Longitudinal study of chronic active human herpesvirus 6 (HHV-6) viremia in patients with chronic fatigue syndrome. Abstract. IDSA. 37th Annual Meeting. Nov. 18-21, 1999. Philadelphia, Pennsylvania. 15. Wagner et al. Chronic Fatigue Syndrome: A critical Evaluation of Testing for Active Human Herpesvi¬rus-6 Infection. Review of Data of 107 cases. Journal of Chronic Fatigue Syndorme;2(4) 1996. 16. 15 Krueger GRF, Ablashi DV and Gallo RC: Persis¬tent herpesvirus infections . Current techniques in diag¬nosis. J Virol Methods 21 : 1- 326,1988. 17. Gerhard Rf et al. Clinical Correlates of Infection with Human Herpesvirus-6. In vivo 1994;8:457-86. 18. Ablashi DV et al. Human Herpes virus and chronic fa¬tigue syndrome. Canad Dis Weekly Rep 1991;17S1:33-40. 19. Albashi DV et al. human B lymphotropic virus (hu¬man herpesvirus-6). J Virol Methods 1988;21:29-48. 20. Josephs SF et al HHV-6 reactivation in chronic fa¬tigue syndrome. Lancet 1991;1346-7 21. Montoya et al. Use of valganciclovir (Valcyte) in pa¬tients with elevated antibody titers against Human Her¬pesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue. Journal of Clinical Vi¬rology 2006;37:S33-38 22. Dylewski J, Chou S, Merigan TC. Absence of detect¬able 1gM antibody during cytomegalovirus disease in patients with AIDS. N Engl J Med 1985; 309: 493. 23. Krueger GRF et al. Overview of immunopathology of chronic active herpesvirus infection. J Virol Methods 1988;21:11-18 24. Krueger GRF, Klueppelberg U, Hoffmann A, Ablashi DV. Clinical corre¬lates of infection with human her¬pesvirus-6. In Vivo 1994; 8:457-86. 25. Nicolson GL, Gan R, Haier J. Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. APMIS. 2003 May; 111(5): 557-66. 26. Buchwald D. et al. A Chronic Illness Characterized by Fatigue, Neurological and Immunological Disorders, and Active Human Herpesvirus Type 6 Infection published in the Annals of Internal Medicine 1992;116:103-113. 27. Lerner AM, Zervos M and Chang CH et al. A small, randomized, placebo-controlled trial of the use of antivi¬ral therapy for patients with chronic fatigue syndrome. Clinical Infectious Diseases. 2001;32:1657-58. 28. Martin W.J. Viral infection in CFS patients. in “The Clinical and Scientific Basis of Myalgic Encephalomy¬elitis Chronic Fatigue Syndrome.” Byron M. Hyde Edi¬tor. Nightingdale Research Foundation Press. Ottawa Canada pp 325-327, 1992. 29. Martin W.J. Detection of viral related sequences in CFS patients using the polymerase chain “The Clinical and Scientific Basis of Myalgic Encepha¬lomyelitis Chronic Fatigue Syndrome.” Byron M. Hyde Editor. Nightingdale Research Foundation Press. Ot¬tawa Canada pp 278-283, 1992. 30. Martin WJ, Zeng LC, Ahmed K, Roy M. Cytomega¬lovirus-related sequences in an atypical cytopathic virus repeatedly isolated from a patient with the chronic fa¬tigue syndrome. Am. J. Path. 145: 441-452, 1994. 31. Martin W.J. Stealth viruses as neuropathogens. Col¬lege of American Pathologist’s publication “CAP Today” 8 67-70, 1994 32. Martin WJ. Stealth virus isolated from an autistic child. J. Aut. Dev. Dis. 25:223-224,1995 33. Martin WJ, Ahmed KN, Zeng LC, Olsen J-C, Seward JG, Seehrai JS. African green monkey origin of the atyp¬ical cytopathic ‘stealth virus’ isolated from a patient with chronic fatigue syndrome. Clin. Diag. Virol. 4: 93-103, 1995. 34. Martin WJ. Severe stealth virus encephalopathy fol¬lowing chronic fatigue syndrome-like illness: Clinical and histopathological features. Pathobiology 64:1-8, 1996. 35. Martin WJ. Stealth viral encephalopathy: Report of a fatal case complicated by cerebral vasculitis. Pathobiol¬ogy 64:59-63, 1996. 36. Martin WJ. Simian cytomegalovirus-related stealth virus isolated from the cerebrospinal fluid of a patient with bipolar psychosis and acute encephalopathy. Patho¬biology 64:64-66, 1996. 10. Gollard RP, Mayr A, Rice DA, Martin WJ. Herpesvirus-related sequences in salivary gland tumors. J. Exp. Clin. Can. Res. 15: 1-4, 1996. 37. Martin WJ. Genetic instability and fragmentation of a stealth viral genome. Pathobiology 64:9-17, 1996. 12. Martin WJ, Glass RT. Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome. Pathobiology 63: 115-118, 1995. 38. Martin WJ. Detection of RNA sequences in cultures of a stealth virus isolated from the cerebrospinal fluid of a health care worker with chronic fatigue syndrome. Pathobiology (IN PRESS) NOT 39. See DM, Tilles JG.Immunol Invest. alpha-Inter¬feron treatment of patients with chronic fatigue syndrome.1996 Jan-Mar;25(1-2):153-64. 40. Brook MG, Bannister BA, Weir WR. Interferon-al¬pha therapy for patients with chronic fatigue syndrome. J Infect Dis. 1993 Sep;168(3):791-2. 41. J K S Chia. The role of enterovirus in chronic fatigue syndrome. J. of clin Path 2005;March 14:1126-1132. 42. Marwan Y. Nasralla, Jörg Haier, Nancy L. Nicolson Garth L. Nicolson. Examination of Mycoplasmas in Blood of 565 Chronic Illness Patietns by Polymerase Chain Reaction.. International Journal Medicine Biol¬ogy Environment 2000; 28(1):15-23. 43. Nasralla M, Haier J, Nicolson GL. Multiple mycoplas¬mal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome.Eur J Clin Microbiol Infect Dis 1999 Dec;18(12):859-65. 44. Gerhard K. M. Endresen. Mycoplasma blood infec¬tion in chronic fatigue and fibromyalgia syndromes. Rheumatology International Issue: Volume 23, Number 5 September 2003: 211 – 215 45. Marwan Nasralla, Ph.D., Joerg Haier, M.D., Ph.D. and Garth L. Nicolson, Ph.D. Mycoplasmal Infections in Blood from Patients with Chronic Fatigue Syndrome,International CFS Conference, Sydney, Australia, 1998. 46. Lerner AM, Beqaj SH, and Deeter RG et al. A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function. Drugs of Today. 2002;38:549-561. 47. Lerner AM, Zervos M and Dworkin HJ et al. New cardiomyopathy: A pilot study of intravenous ganciclo¬vir in a subset of the chronic fatigue syndrome. Infec¬tious Diseases In Clinical Practice 1997;6:110-117. 48. Vojdani A, Choppa PC, Tagle C, Andrin R, Samimi B, Lapp CW. Detection of Mycoplasma genus and Mycoplasma fermentans by PCR in patients with Chronic Fatigue Syndrome. FEMS Immunol Med Microbiol 1998 Dec;22(4):355-65 49. Vojdani, Aristo, and Al Robert Franco. Multiplex PCRF for the Detection of Mycoplasma fermentans, M. hominis, and M. penetrans in Patients with Chronic Fatigue Syndrome, Fibromyalgia, Rheumatoid Arthritis, and Gulf War Syndrome. Journal of Chronic Fatigue Syndrome Vol. T, No. ¾, 1999, pp. 187-197; 50. Vojdani, A, Franco A. Chronic Fatigue Syndrome: Advance in Epidemiologic, Clinical, and Basic Science Research. 1999, pp. 187-197. The Haworth Press, Inc., 1999 51. Choppa PC, Vojdani A, Tagle C, Andrin R, Magtoto L. Multiplex PCR for the detection of Mycoplasma fer¬mentans, M. hominis and M. penetrans in cell cultures and blood samples of patients with chronic fatigue syndrome. Mol Cell Probes 1998 Oct;12(5):301-8 52. Nicolson G, Nasralla M, Franco R, DeMeirleir K et al. Role of Mycoplamsal Infections in Fatigue Illness: Chronic Fatigue and Fibromyalgia Syndromes, Gulf War Illness and Rheumatoid Arthritis. Journal of Chronic Fatigue Syndrome 2000;6(3/4):23-39 back to top of article to click to close                                                                                                                         click here to closeback to top of article


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The following is a fascinating article exploring previous cases of CFS outbreaks, CFS vs myalgic Encephalatitus, and the case for CFS as enterovirus infection. See also CFS
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