A Tale of Two Viruses: Why AIDS Was Pinned to HIV, but Chronic Fatigue Remains a Mystery

By Vincent Racaniello | January 12, 2012 9:46 am

HIV

Vincent Racaniello is Higgins Professor of Microbiology & Immunology at Columbia University, where he oversees research on viruses that cause common colds and poliomyelitis. He teaches virology to undergraduate, graduate, medical, dental, and nursing students, and writes about viruses at virology.ws.

The detection of a new virus called XMRV in the blood of patients with chronic fatigue syndrome (CFS) in 2009 raised hope that a long-sought cause of the disease, whose central characteristic is extreme tiredness that lasts for at least six months, had been finally found. But that hypothesis has dramatically fallen apart in recent months. Its public demise brings to mind an instance when a virus *was* successfully determined to be behind a mysterious scourge: the case of HIV and AIDS. How are these two diseases different—how was it that stringent lab tests and epidemiology ruled one of these viruses out, and one of them in?

The first inklings of the disease now called AIDS surfaced in Los Angeles in the summer of 1981. The 5 June 1981 issue of Morbidity and Mortality Weekly Report described 5 homosexual men with Pneumocystis carinii pneumonia (abbreviated PCP), normally only observed in individuals with weakened immune systems. The article suggested the possibility of an immune dysfunction related to exposure to something that would make individuals vulnerable to opportunistic infections. Soon clusters of PCP and Kaposi’s sarcoma, a rare skin cancer, were observed in gay men in other urban centers. The Centers for Disease Control and Prevention established a simple case definition—Kaposi’s sarcoma or opportunistic infections—and began scouring hospital records. Over time this definition was modified, but its early use identified an ongoing epidemic, and identified groups at risk for the disease as men who have sex with men and injection drug users.

The next year the new disease was called AIDS, and soon the U.S. Public Health Service recommended that members of risk groups not donate blood or plasma. Soon came reports that the disease could be acquired by newborn babies from their mothers, and also by heterosexual contact. By the fall there were nearly 700 people who had been diagnosed with AIDS in the U.S., of whom almost 300 had died. The CDC and World Health Organization worked together to publish global data on the disease, and issue recommendations to prevent its spread.

During the early years, the epidemiology of AIDS suggested an infectious cause, and in 1983, just two years after the disease was identified, a novel retrovirus was isolated from a patient at risk for AIDS. A year later a commercial blood test was developed, which allowed comprehensive studies to be done that showed clearly that the virus, later named human immunodeficiency virus type I (HIV-1), was the cause of AIDS. This conclusion was strengthened by the transmission of AIDS to hospital workers when they inoculated themselves with HIV-containing blood by accidental needle sticks.

By 1987 the first anti-HIV drug, azidothymidine or AZT, was licensed for the treatment of AIDS. Today over 20 anti-HIV drugs have been approved. When given in combinations of three, the emergence of drug-resistant viral variants is minimized, transforming AIDS from a death sentence to a life-long chronic disease.

The story of CFS, generally defined as persistent fatigue of six months or greater not relieved by rest and accompanied by other specific symptoms, is markedly different. This syndrome was first reported in Los Angeles as well, but in 1934. There were subsequent sporadic outbreaks, some of which were reviewed by DA Henderson in 1959, who noted that females were more frequently affected, and suggested that a virus might be involved. In the 1980s Daniel Peterson identified antibodies against Epstein-Barr virus (EBV) in the blood of a group of CFS patients in Incline Village, Nevada. The CDC entered the investigation but was unable to confirm that antibodies to the virus were consistently present in patient blood. A subsequent case-control study failed to identify EBV as the causative agent of the disease, which was subsequently named chronic fatigue syndrome.

The search for that agent of CFS has continued to be fruitless. In addition to EBV, a host of other viruses have been found in CFS patients, including enteroviruses, measles virus, herpesviruses, and human T-lymphotropic virus type II. However, none have been consistently detected in CFS patients and therefore are not considered to cause the disease.

The possibility of a viral cause of CFS re-emerged in 2009 with the detection of a retrovirus called XMRV in the blood of a substantial fraction of CFS patients. A second laboratory subsequently identified sequences related to murine leukemia viruses, also retroviruses, in the blood of CFS patients. However, many other laboratories were unable to replicate these findings, and both papers have been retracted.

Why do the stories of AIDS and CFS have such different outcomes? One reason is that it has been difficult to reach a consensus on a clinical definition of CFS. At the onset the case definition of AIDS was simple—“Kaposi’s sarcoma or opportunistic infections”—which made it possible to rapidly and accurately identify new cases, especially among different research groups around the country. This led to the establishment of risk factors, and the epidemiological data obtained from this work made it highly likely that an infectious agent was involved, spurring the search for the causative pathogen. The case definition for CFS has undergone a number of revisions over the years. When different research groups use different definitions of the disease, it becomes difficult to compare findings. Most importantly, there is no indicator or diagnostic test that can be used to identify CFS, and since diagnosing CFS is a long and difficult process, cohorts established by different investigators vary, leading to different findings, confusion, and contention. In contrast, AIDS was readily identifiable and easily diagnosed once a blood test for HIV was developed.

Another problem is that in contrast to their excellent work on AIDS, the CDC has stumbled when tackling CFS. The CDC has dismissed evidence that CFS is an organic disease, and spent funds on investigating psychiatric and trauma-related causes, rather than infectious origins. The agency also diverted funds designated for CFS to other programs. These and other missteps alienated the CFS patient community—the opposite of what the agency accomplished with the AIDS community.

In part due to the standardized case definition of AIDS, identification of a candidate virus was relatively rapid. Determining its role in the disease was facilitated by the development of a blood test, which could be used to prove that HIV-1 caused AIDS. The relationship between HIV and AIDS was further confirmed by the development of antiviral drugs that inhibited viral replication and helped alleviate the symptoms of the disease.

Why have investigators failed to identify a virus behind CFS? (It is not due to the lack of appropriate technology; this has improved substantially since the 1980s with the development of polymerase chain reaction and rapid DNA sequencing.) One explanation for this dilemma is that an infectious agent does not cause CFS. However, there is plausible evidence for an infectious etiology, including observations that the disease is known to occur in outbreaks. Furthermore, in many cases the onset of symptoms appears to begin with a flu-like illness. Additionally, CFS is a heterogeneous disease, and may be caused by several different agents or a combination of viruses and non-infectious conditions. Another possibility is that an infection initiates an immune response that spirals out of control, leading to CFS symptoms. This scenario implies that at least some CFS patients have underlying deficits in immune regulation. If that’s true, it will be very difficult to identify the virus involved because it will likely have been eliminated from patients’ systems by the time CFS symptoms become apparent.

In retrospect, it is clear that the properties of AIDS made it an easy disease to understand. While the path to understanding CFS has been clouded by non-scientific issues, in the end the main reason why we do not understand this disease is because it is extraordinarily complex. But that never stopped a good scientist.

Image: HIV (green) budding from an infected cell. Courtesy of C. Goldsmith / CDC

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  • Kelly Latta

    Another difference between HIV/AIDS and ME/CFS is the amount of money spent on research. Currently the main funding in the field of ME/CFS comes from philanthropic individuals.

    Since 2007, the NIH has spent/allocated between $2,096 million and $3,086 million on HIV/AIDS research.

    In contrast the NIH has spent/allocated between $4 million and $6 million on ME/CFS research during the same time period and the CDC budget is no higher. As well, the CDC CFS research program, housed in the Division of High Consequence Pathogens, may well be the only program in the division that does not conduct research into pathogens.

    Inadequate funding, more than anything else, may stop good scientists from unravelling such a extraordinarily complex disease.

    Without a commitment of substantial biomedical funding in addition to psychosocial funding, it is irrational to expect medical knowledge to advance in any disease – but particularly in the case of such a complex disease.

  • http://www.brokenmarionettebook.com Maija Haavisto

    The article should mention that the enteroviruses have first been implicated several decades, before the herpesviruses. There is a considerable amount of evidence for both. Especially the antiherpesviral studies seem very promising, even if it turns out the herpesviruses aren’t ultimately causative – some patients in the studies nonetheless seem to have fully recovered with the antivirals.

    Many CFS/ME experts believe herpesviruses can’t be the root cause, since their incubation period doesn’t really match what’s known about the epidemics, which would better match with enteroviruses. Hopefully we’ll have more evidence soon, with several groups studying both types of viruses and their treatment.

    There is also some evidence for the role of parvovirus B19, which could form a subset of CFS/ME. It is quite likely that several viruses can cause an illness with similar symptoms, which can be further complicated with other chronic or reactivated viral infections and some bacteria, as well.

  • ECW

    Re #1, Kelly Latta;

    A more accurate comparison on funding differences would be what was being spent on AIDS research in 1981 or 1983. Funding in 2007 reflects decades of knowledge regarding HIV and AIDS, and the huge impact it has had in the healthcare of millions of people. Also, something that kills probably will always have an easier time getting attention, and funding.

  • ErikMoldWarrior

    http://articles.latimes.com/1986-06-07/news/mn-9956_1_lake-tahoe
    160 Victims at Lake Tahoe

    Chronic Flu-Like Illness a Medical Mystery Story
    June 07, 1986|ROBERT STEINBROOK

    “…And last fall, two investigators from the federal Centers for Disease Control spent several weeks here looking into the mystery. They concluded last week that they could “neither prove nor disprove” the relationship between the Tahoe illnesses and the Epstein-Barr virus.

    Finding Challenged

    That finding was immediately questioned by Dr. Paul R. Cheney, one of the two doctors who has been treating the patients. He said the investigation was too narrow and has been overtaken by subsequent developments.

  • Tony Mach

    @Maija Haavisto:

    Plus there is the finding of Enterovirus VP1 protein (and high neutralizing antibodies against Enteroviruses) by some groups. Plus the Nora Chapman theory about how it could come to a persistent “non infectious” Enterovirus infection.

    Let’s see what Lipkin finds, then we need to take the next step from there

  • Jon

    There is only one difference between AIDs and CFS.

    AIDs is a real disease that results in death if not treated. CFS is not a disease at all.

  • L. Hart

    AIDS WAS NOT an easy disease to understand at all. Money and tools help. If XMRV is dead, why are there so many publications being published each week? Good ones, examining how it works, what each part does, how it assembles itself. It exists independent of some labs ability to contaminant their cell lines with it and other virions. We know that there are lung and other tissues which secrete XMRV (see literature). We know it takes a different path through the B Cells than AIDS to unhinge the immune system checks and balances. We know many viruses are able somehow, once the back door of the protective immune system is unlocked, get in-HHV-6 EBv, scads of others. We know some integrate into DNA, to be activated another time. Herpes Simplex does a great job of reappearing as Zoster. We know in ME/CFS that a door to the immune system is opened by something viral and we know more and more how that door is opened and more how the immune system is hijacked. We know EBV, unchecked leads to cancers, we know other viruses lead to cancers. We are only a few years into the new leads the 2009 Mikovits paper has given science to explore. There was nothing wrong with the work from the laboratories in that paper except Silverman’s lab (and Dr. Silverman didn’t even apologize for the sample mixup-although he did have a sample of the real thing.). Presently, money with commitment and time will show much us much more. Better and more specific tools are developed, as they were and are with ongoing AIDS research-AIDS research has never stopped. So-it begs the question-where is the money, CDC? Why the waste on studies that seek to blame the patient? Disease is real, and the only way disease is in someone’s “head” is because the infectious qualities and downstream products do cross the blood brain barrier, and can make parts of the brain a reservoir (WNV, others). We have many clues and many models. Politics doesn’t belong in science, as most of the politics is the fruit of vanity and ego in competition for status rather than benefiting the people of this nation. Why the dumbing down is condoned &/or tolerated and even embraced in medicine and science is not rational nor financially sensible. At the very least, science and medicine can help the victims of ME/CFS have greater functionality, and keep exploring the great gifts research has so far brought us.

  • Chris N.

    A couple of memories:

    1) A nurse’s needle stick:

    http://news.google.com/newspapers?nid=1144&dat=19910131&id=9RwhAAAAIBAJ&sjid=32MEAAAAIBAJ&pg=1655,7032456

    2) DeFreitas’ CAV HTLV-II-like retroviral fragments, #WO9205760. ‘Would have liked to see WPI pick this up work.

    Case definitions – ironically that’s one thing the Lombardi XMRV study was not hindered by. But the CDC, and especially Dr. Unger’s non-viral virus unit in Atlanta, remains determined to stick with the garbage categorization they’ve promoted for two-plus decades, and prolong the confusion. Few are trying harder not to solve the problem.

    IMO, although many sincerely believe ME/CFS to be autoimmune, without access beyond the blood, that’s a presumption others find all too convenient. I don’t see why one can’t have an autoimmune condition perpetuated by active infection as well as environmental agents.

  • http://www.laurenceswift.co.uk Laurence Swift

    It doesn’t take much thinking to work out that if there is an undiscovered virus present which can affect the immune system, similarly to the situation in AIDS, then other viruses can run riot unsuppressed, such as EBV, Parvo, CMV, herpes (HHV6), etc. This is the picture we see in cases of ME (CFS).
    My second point is that in his eighth paragraph, last sentence, Mr. Racaniello uses the phrase “were unable to replicate these findings”. “Replicate” is the wrong word. To replicate anything, especially lab work, you have to follow the exact same methods and protocols of the original. Not one study so far has even attempted to do this. The “gold standard” for finding a new virus is to grow it in tissue culture. This was done by the original research team to find the XMRV virus. This team also took great steps to avoid any contamination. More recent attempts to find the virus relied merely on the cheap and easy PCR techniques. Unfortunately these are very prone to contamination of tissue culture cells, and the XMRV virus does tend to masquerade as a contaminant since it is related to a whole group of gamma-retroviruses mainly mouse-derived. Sorting this lot out should be a top priority, because it appears that XMRV (or whatever you call it) may be the answer. This is common sense and would show that ME (CFS) is a no more complex or multifactorial than is AIDS.

  • C. Eckerle

    Bravo, a fair and accurate account of the facts. It is heartening to see that intelligent people understand the nature of this controversy these days. It’s been a LONG time coming.

  • Simon McGrath

    A thoughtful and very interesting account, thank you. ME/CFS needs more intelligent analysis like this.

    Ed. note: ME/CFS = myalgic encephalomyelitis/chronic fatigue syndrome

  • http://blogwormwood.blogspot.com Alison

    The largest hindrance to CFS research is the problem actually identifying patients.

    What about the two day exercise test? Right now CFS is mainly defined as fatigue lasting more than six months, but on the CDC website, the second symptom is post-exertional malaise. This is measurable by a two day exercise test, like those being done at the Pacific Fatigue Lab at the University of the Pacific in Stockton.

    Granted, it’s not as easy as a blood test, but it is something to help identify patients concretely and should be looked into more by CFS researchers and the CDC.

    More about the work at the Pacific Fatigue Lab: http://aboutmecfs.org.violet.arvixe.com/News/PRJan09Pacific.aspx

  • Andrew Crowns

    The virus first entered the human population in 1951.
    American retrovirologists ignored it because their dogma was that retroviruses could not infect humans.
    In 1991 only 40% of labs could reliably detect the virus in infected people. Latent HIV is very difficult to detect in blood even to this day.
    Latent virus is activated by infections and vaccines which raises the titre quite significantly for a short time allowing easier detection.
    At any one time only some two percent of the total HIV population is found in blood.
    Hiv is frequently detected using lymph node extracts and can be found in tissues readily when virtually undetectable in blood. Specialised primers and cycling conditions are needed to reliably detect HIV in blood by PCR and even to this day diagnosis is made by elisa confirmed by western blot.
    Gallo was found guilty of scientific misconduct by a committee in 1994 and his papers to contain fraudulent claims. His papers were not retracted by Science magazine, even though fraud was alleged for 14 years before this hearing.

  • Ann

    To Jon, who states that “CFS is not a disease at all” – I hope you never learn differently. I’ve lived with this “non-disease” for 9 years, and I wouldn’t wish it on anyone. It is heartening to see that attention is finally being paid to this debilitating illness, and I’m looking forward to seeing Lipkin’s results.

  • Alex Young aka alex3619

    In reply to: . “Jon Says: January 12th, 2012 at 2:27 pm There is only one difference between AIDs and CFS. AIDs is a real disease that results in death if not treated. CFS is not a disease at all.”

    This is a technicality. CFS is a syndrome and a number of definitions describe a heterogenous patient mix. The core disease that has occured in many geographical clusters (epidemics) is Myalgic Encephalomyelitis. The number of biophysical abnormalities is huge (thousands), but not routinely tested for – indeed most pathology labs do not even have the required tests.

    Let me give some examples of these things to give an idea of the issues:

    1. Many with long term ME have heart damage. It is now apparent that this kind of damage might be unique to the disorder, but for most of the last ten years this was confused with regular diastolic heart failure/dysfunction. Heart biopsies frequently find viral infection when the biopsy is done, but biopsies are rare.
    2. Abnormal immune chemistry abounds. Take for example 37 kDa RNase L. It is found in most ME patients. It is also found in MS and Rheumatoid Arthritis patients, so it is not diagnostic. Most of the abnormal chemistry is shared, and so not diagnositc.
    3. Three abnormal findings have high diagnostic value and await validation: spectral coherance EEG (Komaroff); post exertional pathophysiology (Pacific Labs, Lights) and severely decreased NK cell function with a low bright cell to dim cell ratio (Bond University).

    This latter makes ME a type of non-HIV AIDS affecting NK cells and not T cells – different, but not entirely different. ME has much lower mortality in the medium and short term, but the long term is questionable – it doesn’t kill as fast, but it does kill. Lymphoma is very common in ME patients, and some cases of Karposi’s sarcoma have been claimed, normallly found in HIV AIDS. However, ME morbidity is similar to HIV AIDS morbidity shortly before death – ME is much more disabling during most of the disease history. Imagine feeling like an AIDS patient weeks before death, but it goes on and on and on for years and decades.

    Bye, Alex

  • Jack

    Totally echo what C. Eckerle says above. An excellent summary. And thanks to Prof Racaniello once again.

  • http://theinfectiousmyth.com/ TBrewster

    I don’t know how anyone in the world would trust anything that the Center’s for Disease and Control or the National Institute of Health would have to say about human disease. The same ol preached sermon, the same ol boring article full of gaping holes on how and where “AIDS” began. Chronic Fatigue Syndrome is *PROBABLY* another phony syndrome just like “AIDS”. never mind “HIV” who the hell has it?

  • http://p-a-n-d-o-r-a.org/ Tina

    Thank you for this report. Many good points by you and the commenters (except Jon).

    The people dying relatively soon after symptom presentation is a factor. The lack of CDC response was certainly a factor. The complexity / multi-system aspect of the disease is a factor, lack of research funding is a big factor, no physical signs, only subjective symptoms. The latent virus activation varying from patient to patient, and also being subjective to the standard of those who read the tests was a factor.

    No one has mentioned this, but sexism is a factor. The idea of many is that women are more sensitive to exaggerating symptoms or to developing physical symptoms from stress, or to hysteria (what the CDC guy over CFS research said to the PrimeTime producer as the cause of the Incline Village outbreak).

    Also, the fact the diagnostic criteria is that the person have the symptoms for six months makes finding the initial cause or trigger very difficult.

    I think the fact this disease is up and down means the body is struggling to get normal function. This may explain inconsistent results in studies as good days may have the disease mechanism suppressed and a bad day has it active.

    Another factor, while CFS appears to have occurred in outbreaks back to the 1930s, as you described, the one that got news media attention was in the 1980s, while the country was putting all resources toward the other new illness, AIDS. CFS was competing and lost.

    Why CFS advocacy has been challenged compared to AIDS is a whole nother story. But it is a factor on the lack of response.

    I have often said, “Why can’t I have a normal disease with normal researchers?”
    And, “I wish my pee were blue.” (This is because a doctor would not dare think I am exaggerating my pain and fatigue and other symptoms if he could see something abnormal, like blue pee.)

  • Lourdes

    Can a test of the markers for immune system of CFS patients not serve as a means of diagnosis (level of Immune-deficiency)?

    A disease that renders its sufferers disabled is much more of a cost to society than one that kills. Hate to sound heartless but the post about Aids being more deserving of attention and funding is very illogical and insensitive.

  • http://niceguidelines.blogspot.com/ Dr Speedy

    Dear Prof Racaniello, thank you very much for this excellent article.

    The search for the infections agent that causes CFS however has not been fruitless, this search has been almost totally absent.

    The CDC and the CBT psychiatrists, first changed the name of this disease from Myalgic Encephalomyelitis to Chronic Fatigue Syndrome, and then they also changed the criteria to make sure that no one would find out what a severely disabling disease this is. They also made sure that all the money to research this disease was either diverted or used for psychobabble. Over the last few decades, no research has been done by the major institutions to use the new techniques you mention to find the causative agent. Only a few dedicated doctors like Dr. Petersen and Dr. Ghia have tried to find the virus, but they lack the resources of the major institutions.

    If one wants to find the virus, one should select a group of patients with very severe ME i.e. patients like myself who have been bedridden and are totally dependent on others for years on end. Even a six-year-old, with his eyes closed, can tell the difference between a patient who is bedridden with very severe ME and a patient who is bedridden with depression or another psychiatric problem.

    6. Jon Says:
    “There is only one difference between AIDs and CFS.
    AIDs is a real disease that results in death if not treated. CFS is not a disease at all.”

    This sort of response is not surprising after decades of nonsense propaganda by the CDC and the CBT psychiatrists. There are about 5000 medical research publications, demonstrating that ME/CFS is a physical disease. Most have demonstrated immunological abnormalities, ongoing viral infections and mitochondrial abnormalities.

    It’s also clear that Jon is not aware of the fact that there is a Highly increased incidence of non-Hodgkin’s lymphoma in HIV/AIDS and also in ME/CFS, that he is not aware of the fact that the incidence rate of non-Hodgkin’s lymphoma is 0.02% in the United States, yet nearly 5% of ME/CFS patients develop the disease and also that almost 5% out of a group of 752 ME/CFS patients, contracted ME/CFS from a blood transfusion.

    Furthermore, it seems that he’s not aware of the fact that for example Alison Hunter officially died of ME/CFS in the late 90s, Annabel Senior officially died of the disease in 2003 and Sophia Mirza officially died of this disease in 2005.

    How strong the psycho stranghold of this disease is, has recently become clear again in the UK with the Medical Research Council announcing what they are going to do with another £1.6 million which was supposed to go to biomedical research into ME/CFS. Two projects are again looking at psycho nonsense, another one is looking at Sjögren’s disease, so diverting money is still happening in the UK as well, and not one penny is being spent on trying to find the cause of this disease. Which is not surprising really, as the MRC is controlled by CBT psychiatrists, who don’t want the world to find out what a severely disabling physical disease this is.

    So thank you again Prof for setting the record straight.

  • http://www.virology.ws Vincent Racaniello

    The amount of money spent on a disease for research is driven in large part by how much progress is made. When HIV-1 was discovered, huge amounts of money were allocated for its study because there were so many clear paths. At one point there were seven study sections at NIH reviewing AIDS grants, and one study section for the rest of virology. That caused consternation as you might imagine. If XMRV had panned out as a CFS cause, you would certainly seen much more money poured into CFS research. It’s a chicken-and-egg problem, but that is the way science works. When you get an NIH grant, you are expected to use some of the money to explore ‘other areas’, and if you get interesting results, they can be used to secure additional funding.

  • Kelly Latta

    @Jon

    There are over 4,000 research papers in the scientific peer-reviewed literature that say you are wrong. I am assuming you weren’t an author on any of them. Unfortunately this is a drop in the bucket compared to AIDS research.

    While everyone is entitled to an opinion scientists and many others prefer actual evidence to support the opinion or at least expert opinion such as Dr. Racaniello’s.

    In a New York Times interview in 2009, Dr. Nancy Klimas who has researched ME/CFS since the early 90s and treats both HIV and CFS patients, responded to reader who had a opinion similar to your own. She said, “…I hope you are not saying that C.F.S. patients are not as ill as H.I.V. patients. My H.I.V. patients for the most part are hale and hearty thanks to three decades of intense and excellent research and billions of dollars invested. Many of my C.F.S. patients, on the other hand, are terribly ill and unable to work or participate in the care of their families.

    I split my clinical time between the two illnesses, and I can tell you if I had to choose between the two illnesses (in 2009) I would rather have H.I.V. But C.F.S., which impacts a million people in the United States alone, has had a small fraction of the research dollars directed towards it.”

    @EWC

    For the record: Federal AIDS funding went from $200,000 in FY1981 to an estimated $3.85 billion in FY1999. In the case of ME/CFS, according to the GAO since fiscal year 1987, the NIH devoted approximately $57.6 million to the study of CFS through intramural and extramural CFS grants. Not exactly equivalent.

  • John Bochenek

    Two thumbs up for knowing the history of the disease and an open-minded approach to a difficult scientific problem. Both are necessary for research to succeed.

    After eight years living with and researching CFS, I believe that it is a neoplasm (similar to mastocytosis in some respects) and likely put into motion by an infectious agent. In the majority of patients with mastocytosis or CFS, the condition is benign, while some eventually wind up with a malignant form. Both are related to an immune dysfunction, but the overactivity is in different branches of the immune system. This leads to different sets of symptoms (with some overlap). Both are notoriously difficult to diagnose and have subsets of patients which cloud the diagnostic picture further.

    Thank you for your work in this field which has utterly destroyed the lives of many.

  • http://cfsmirror.blogspot.com/ In Vitro Infidelium

    VR wrote:” Hoever, there is plausible evidence for an infectious etiology, including observations that the disease is known to occur in outbreaks. Furthermore, in many cases the onset of symptoms appears to begin with a flu-like illness.”

    There is a double dose of a priori reasoning being applied here. There is no secure epidemiology that can reliably demonstrate commonality of illnes either within reported outbreak cohorts, or between outbreak cohorts; in addition the linkage of ‘symptom onset’ is a feature wholly of patient report, not of any validated assessment. That is not to say that outbreaks are not representative of occurences of highly localised epidemilogical features of M.E/CFS, nor that M.E/CFS is not characterised by an acute onset, but at this stage these remain speculative features, not definitive descriptions.

    While an event characterised by multiple individuals displaying symptoms of a communicable infection which is followed by a chronicity of symptoms that are typical of M.E/CFS is clearly suggestive of an involvement of infection within the aetiology of M.E/CFS, there are simply too many confounding factors to allow a conclusion that M.E/CFS is unequivocally explained by an infection mediated aetiology. It must be asked that “if the assumed infectious agent is active in a given population, then what proportion of that population will becom infected, what proportion of those infected will display acute symptoms and what proportion of those who are a) infected and asymptomatic b) infected and display an accute symptomology go to develop a chronic condition that is describable as M.E/CFS ?” If we were talking about HIV, the answer to the third part of the question is would be something close to 100% for both a) and b), yet we have no such evidence in the M.E/CFS that infection necessarily equates to chronic disease. In the case of M.E/CFS infection appears only to be associative, not directly causative, something which is echoed in one of the few epidemiologically consistent observations of M.E/CFS patients, that is, there is a strong imbalance in gender representation – women being diagnosed at a much higher rate than men. Unless a very unusual exposure process is in play, then the gender imbalance issue is a major stumbling block for any hypothesis of M.E/CFS that is founded on a purely infectious causation.

    The patient reported association with acute onset coincident with a viral infection is also problematic. It is of course axiomatically impossibe to have planned a prospective test of a patient’s health prior to their reporting illness, and the patient’s observations may well be important evidence. However it can not be discounted that there may have been low level symptomology present prior to an acute infection, with that symptomology being entirely independent of any infection, or alternatively that an infection may be a trigger for an underlying but asymtomatic condition. Given the level of disbelief which has histerically met M.E/CFS patients encountering medical services, there may be very strng predisposition for patients to locate the commencement of chronic illness at point that is coincident with an accepted state of illness in the very natural attempt to provide validity for their very real chronic illhealth.

    M.E/CFS is a complex illness that demands significant commitment of research effort, that effort can not be short cut by poorly stated hypotheses, and only through research which is conducted in relation to the known characteristics of the illness can real progress be made. M.E/CFS most certainly is not like HIV, it is nevertheless a debilitating illness and the lack of progress in understanding it undoubtedly raises questions about the perspectives of the medical profession, the research fraternity and polititions.

  • Alex

    In contrast to In Vitro’s claim, the association of CFS with viral infection is not merely based on retrospective self-reports of patients. Prospective, longitudinal studies have shown that a stereotyped CFS syndrome develops in a small percentage of patients exposed to a number of serious intracellular pathogens, and that the severity of the acute infection (rather than say, psychological or personality variables) is by far the strongest predictor of CFS case-ness at 6 and 12 months. In the elegant Dubbo studies, researchers identified confirmed cases of acute infections with EBV, Coxiella Burnetti, and Ross River virus and found that a for a certain percentage of patients who come down with these infections (about 10%), CFS-like symptoms develop in a stereotyped pattern as the acute phase of the illness resolves, and a few (3%) remain ill indefinitely. Other teams have subsequently confirmed, using prospective designs, that this finding extends to subjects afflicted with acute infection with the SARS virus, and the pathogen that causes Lyme disease.

    In contrast, investigators using similar prospective designs have found that “minor” infections such as upper respiratory infections and influenza do not result in an increased risk of developing CFS.

    It is not clear why a small percentage of patients afflicted by these serious acute infections do not recover. However, there is probably an inherited defect in immune regulation that makes these patients predisposed to develop the syndrome. The familial component in CFS appears to be stronger than in most chronic diseases, and risk of getting CFS is elevated in first, second, and third degree relatives of cases.

  • Domingo Escudero

    Very interesting discussion. I am convinced ME CFS is related to some kind of retrovirus or HERV and has a lot of similarities with Sjogren’s syndrome.

  • Flo Henson

    Yes, Dr. Speedy. Even a six-year-old can tell that a patient who is bedridden and totally dependent on others for years on end is sicker than a patient who can dress, prepare his own food, drive a car, and go to work or school or a doctor’s appointment.

    Yet it is the latter group of patients who are recruited for research studies. What a terrible mistake!

  • Kelly Latta

    @In vetro infedelium -

    Dr. Ian Lipkin has suggested that ME/CFS is a rare reaction to common pathogens. As well, we don’t know why autoimmune diseases affect fewer men than women in general either, but viruses have also been implicated in a number of autoimmune diseases.

    Or it could be that men are underdiagnosed and women overdiagnosed for cultural reasons thus throwing the epidemiology off.

    Or it could be, as some scientists have hypothesized, that ME is actually multiple discrete entities grouped together for the sake of convenience as was done in the early days of hepatitis research.

    You state that patients may assume an infection in order to “validate” their experience or because it matches their history, but that doesn’t explain why viruses have been found in subgroups of patients. Lack of replication may be because multiple definitions are used to define cohorts making extrapolation between them impossible.

    Nor does it explain why many of the researchers who study viruses continue to believe there is a viral component to ME/CFS. The authors of Shin et al 2010 concluded, “It is also vital to state that there is still a wealth of earlier data to encourage further research into the involvement of other infectious agents in CFS, and these efforts must continue.”

    You also note that low level symptoms may be present prior to an acute infection – and indeed the literature does include the kindling theory.

    Lots of questions. Answers? Not so much.

  • JD

    Thank-You to Prof Vincent Racaniello for this well-reasoned and rather comprehensive article!

    I would only mention two things, first the definition issue is mostly IS the issue. It is great to see it focused on and it arguably deserves even more, much more, focus.

    Some definitions have only the requirement of “Chronic fatigue, 50% of the time” whereas others require unique constellations of signs and symptoms (for example, the International Consensus Definition 2011) such as post exertional collapse, unrefreshing sleep, muscle pain, and a host of others.

    We cannot say much about which viruses are or aren’t associated with this terrible condition until a consistent and uniform definition is used. Most of the old definitions or the popular definitions obviously don’t select a uniform group whereas some of the newer ones either would, or would certainly come much closer.

    As for the retrovirus issue, I would just like to point out that Dr. Mauren Hanson of Cornell, found antibodies to retrovirus in 50% of her ME/CFS patients and 15% of controls using a Whittemore Peterson Derived Western Blot. Therefore, I believe the retrovirus hypothesis should not be completely abandoned whatever has happened with MLV/XMRV as it is would provide such a strong framework and intuitively “make sense.”

    Alternatively, its possible that this is due to over-activation of the B-cell component of adaptive immunity: this viewpoint is supported by the recent Fluge and Mella study finding that a B–cell depleting drug was very effective in ameliorating symptoms in a large subset of patients.[2]

    1.) IACFS/ME Conference Abstracts 2011.
    2.) Fluge Ø, Mella O et al. Benefit from B-lymphocyte depletion using the
    anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and
    placebo-controlled study. PLoS One. 2011;6(10):e26358. PMID: 22039471; PubMed Central PMCID: PMC3198463.

    Thank-you to Dr. Racaniello for this example of balanced and thoughtful science journalism.

    Hopefully in the future the definition issue will get more attention. It is crucial. It would be the equivalent of zoologists calling Mice and Elephants both “Elephants” –some definitions are literally that bad.

  • acer2000

    In Vitro Infidelium: You always post the same thing trying to counter the suggestion that there is significant evidence evidence that CFS is infectious and communicable. There *is* such evidence in abundance. Many outbreaks have been documented over the past 100 years. In fact, in the 1950s they injected blood from CFS from the patients into monkeys and the monkeys came down with symptoms. (Perhaps someone should repeat that experiment and pay close attention using today’s molecular diagnostics) There are also reports of nurses coming down the CFS symptoms following needle sticks after drawin CFS patient blood. Also, if you talk to the physicians with the most experience with ME/CFS, they will tell you that the symptoms, signs, onset, and history among patients presenting with “CFS” have more in common than they don’t. This suggests that while CFS may have more than one or two cardinal symptoms and this may be confusing or complex on the surface, it isn’t in fact a heterogenous disorder – its just an illness that has more than a few symptoms associated with it, consistently.

  • JD

    RE: the person saying this is a psychological disease–that is not the case. There is a ton of research supporting the viewpoint of a biomedical disease brought on by a flu-like infection.

    However, the definition issue, makes it hard to debate even this basic point. Some of the definitions such as the 1991 Oxford (which is the one that requires only “50% chronic fatigue” ) almost certainly capture people who are mostly “tired” due to this or that psychological reason.

    Contrast this definition with the recent International Consensus Definition:

    “Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles AC, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisbik S, Mena I, Mikovits JA, Miwa K, Murovska M, Pall ML, Stevens S. J Intern Med. 2011 Oct;270(4):327-38. doi: 10.1111/j.1365-2796.2011.02428.x. Epub 2011 Aug 22. Review. PMID: 21777306″

    I would also like to comment, this is the *only* area of Science where I have ever seen people stridently argue for looser, less accurate, and less specific criteria. Most of these people are British Psychiatrists who have invested their careers in a certain theory of this illness (the Peter Duesenbergs of Myalgic Encephalomyelitis, so to speak)

    … it is my opinion they should be ignored, or one should proceed in anyway case as one always should proceed in science, with the most accurate and most sensitive instruments and ignore the arguments for less sensitivity and less specificity.

    Arguing for open-ended, interpretive “post modern” methods and tools … is antithetical to the very heartbeat of science, not matter who makes these arguments…

    Interestingly, Hillary Johnson who covered the Tahoe Epidemic, has kept a list of people she interviewed with this illness, and a significant portion of them have died untimely deaths due to medical problems(though it *is* rare, for the cause of death to be attributed to ME/CFS directly) in her blog “OslersWeb”.

  • acer2000

    References –

    Med J Aust. 1955 Sep 24;2(13):480-2. Further investigations on a disease resembling poliomyelitis seen in Adelaide. PELLEW RA, MILES JA.

    http://www.ncbi.nlm.nih.gov/pubmed/13272481

    Postgrad Med J. 1978 November; 54(637): 711–717. Early outbreaks of ‘epidemic neuromyasthenia’. J. G. Parish

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425322/

    Br Med J. 1978 June 3; 1(6125): 1436–1437. Epidemic myalgic encephalomyelitis.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1604957/

    Martin, WJ and Glass, RT. Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome. Pathobiology 1995, 63, 115-118.

    http://www.ncbi.nlm.nih.gov/pubmed/8821627

    and others…

  • Bella

    Feeling toxic, as if poisoned, is my main symptom. The term ‘chronic fatigue syndrome’ doesn’t describe this feeling of being iller than I ever thought possible.

  • Rivka

    I, too, have the symptom of feeling like poison is coursing thru my veins. This is how my illness started 22 yrs ago, and a main symptom I still have today, along with being bedridden and home bound much of the time.

    I like this article, but did feel that the first paragraph, where it says we are tired does not describe this illness at all. If what I have is mere tiredness, then why is it that I wake up each morning (for 22 years) unable to get out of bed, even after I have rested a full night. Everyone in the USA is tired and overworked. No, I am not “tired” or fatigued; I am very very sick and severely disabled.

    I hate the name of the illness: chronic fatigue syndrome. What a joke. The belittling name alone has held us back more than anything else.

    For those who can, it is time to ACT UP, like the HIV/AIDS community did so many years ago. That got the attention of the NIH (read: Fauci). The squeaky wheel gets the most attention. Here is a video of some patients from around the USA demonstrating outside and in front of the Health and Human Services building in Washington DC, on Capitol Hill. http://www.youtube.com/watch?v=_elj8mcd9Ak

    We need demonstrations like this to be held in front of all the CDC and NIH and HHS buildings in the USA. Then maybe we’d get the attention and research funding a group of 1 million very sick and disabled Americans deserve. Certainly then we’d get more than the $4-6 million per year we get now. (Which is not much more than Hayfever research gets funded.)

  • https://twitter.com/#!/janwly Janelle

    Thank you, Professor Racaniello, for so clearly explaining some of the important issues here.

  • http://cfsmirror.blogspot.com/ In Vitro Infidelium

    @Alex. You have mischaracterised what I wrote; I did not claim that there was no evidence (other than patient report) of ‘association’ between infection and M.E/CFS, and indeed at several points I acknowledged that such an ‘association’ exists. What I did claim was “the linkage of ‘symptom onset’ is a feature wholly of patient report, not of any validated assessment.” The Dubbo papers do not in anyway mitigate the problems that arise from the lack of pre acute illness assessment; by its very nature the starting point of the Dubbo set is ‘acute’ illness. Dubbo was too small to provide any meaningfull epidemiological data but certainly it provides a reasoned basis for an hypothesis of Post Viral Syndrome, the question then becomes: “Does PVS = M.E/CFS or is PVS a subset of a broad M.E/CFS spectrum of illness, or are there distinct aetiologies associated with specific infections resulting in rare case of chronic illness ?”

    The Dubbo data would have broad application to M.E/CFS if a preponderance of M.E/CFS cases followed confirmed serious infections, but that simply is not the case, the patient reports of acute onset are not predominantly of illnesses that would require physician attendance, and must therefore be assumed to fall into that class of, as you quote: “investigators using similar prospective designs have found that “minor” infections such as upper respiratory infections and influenza do not result in an increased risk of developing CFS.” There is a further problem with using the Dubbo work as broadly applicable to M.E/CFS , that is: EBV alone (setting aside Coxackie B, SARS etc) is a highly infectious agent and spreads rapidly through, and is near universially present in, modern human populations, maximal exposure is in the teenage years which is where a PVS characterised illness would be expected to be most evident – yet this is not the case instead M.E/CFS is characterised by an age profile heavily weighted to a +35 age group.

  • http://cfsmirror.blogspot.com/ In Vitro Infidelium

    @Acer. At no point here or anywhere else have I claimed that infection has no role in the aetiology of at least a subset of M.E/CFS diagnoses. Your arguments are unfortunately circular or relate to data that is inconsistent or anecdotal. The reason I have repeated the same observations in a number of fora is because the discussion of M.E/CFS is consistently undertaken without reference to key characteristics of the illness as it described by application of all the currently presented sets of disease criteria. Foremost amongst these ‘inconvenient characteristics’ are the gender imbalance and the age profile; in the absence of contrary epidemiological data, any proposed hypothesis of M.E/CFS aetiology has to be made with cognisance of these defining characteristics. If infection were to be the only source of pathology in M.E/CFS, then we are looking for a pathogen that preferentially (if not exclusively) infects woman in their 40s and 50s – this seems a somewhat improbable scenario.

  • Alex Young aka alex3619

    I am the other Alex, there are two on this page.

    I am in partial agreement with in vitro in post 33. There is still insufficient evidence to equate post viral fatigue with ME. They may not be the same thing. This is one of the problems we face. Are we talking about one or several discrete but similar diseases? Are we talking about one disease with a spectrum of manifestations? Are we talking about as subset of post viral fatigue becoming ME? (I think this latter case is the most likely at this point.) Without reliable biomarkers the research can never really address these questions.

    Confusion between PVFS and ME may also be responsible for much of the uncertainty over prognosis. For example, most cases of PVFS resolve themselves in a few months to five years at the outside. Looking at data over the five year mark, most long term ME patients never recover. If the under five year data is a combination of ME and PVFS this would explain the discrepancy. Since most people see those with PVFS recover, it would also explain why they do not understand why those with ME do not. But is this explanation correct? We need biomarkers to proceed.

    Bye, Alex

  • Jack

    Am not disagreeing with you Alex, but PVFS and ME may also have the same problems associated with them as those raised by In Vitro and indeed Prof Racaniello above.

    Proving PVFS is as hard as proving CFS, CFS/ME or if you like ME. PVFS ought to require the proven presence of a viral agent but this is not always the case and the criteria for PVFS are very similar (if not the same) for CFS at present.

    And why do only a fraction (in my opinion) of folk ‘develop’ PVFS when the majority of folk seemingly recover? Smacks more of something to do with immune dysfunction and other issues than with a persistent viral infection in some if not all cases.

    I do not believe we can ‘chase viruses’ per se or that any one virus is responsible not until we solve the very confusion spoken of in the article and explained further by In Vitro.

    Of course creating subsets that are hopefully more relevant to clinicians and researchers (if we are saying existing parameters are too broad) may not result in the viral aetiology that some believe explains the ‘resultant’ symptoms.

  • Alex

    @In Vitro, I’m not sure where we actually disagree.

    I don’t support the contention that CFS has a “purely infectious” etiology but I would remind you that no disease is “purely infectious”. It is always a question of the balance between the infectious agents in the environment and genetic adaptation of the host. For example, there are some individuals in the population who never develop AIDS after exposure to HIV, because they have a resistant genetic background. If an infection like HIV had afflicted the human population in the pre-medical era, one possible outcome would be that a number of generations of natural selection would render almost the entire population HIV-resistant. With reference to this population, HIV would be seen as a “harmless” bug that almost everyone gets, and the few people who lacked the genetic resistance would be seen as abnormal.

    I support the following hypothesis of CFS: individuals with CFS have genetic polymorphisms that cause their innate immune response to be slower and less efficient in responding to certain intracellular pathogens than individuals lacking the predisposition. The immunology study of the Dubbo cohort suggested that the individuals who did not recover took significantly longer to develop a specific immune response to the pathogens; this would give the pathogens more time to spread to other tissues and trigger inflammation in the central nervous system. Once inflammation in the CNS is triggered, changes in brain plasticity cause the illness experience to become chronic. The ongoing inflammation may or may not be due to a failure to clear ongoing infections. Natelson and Baraniuk’s studies on cerebrospinal fluid suggest that CNS inflammation is present.

    Cross-sectional studies of CFS patients (i.e. Komaroff et al) in the chronic phase have shown that some have elevated rates of herpesvirus reactivation when sensitive methods that distinguish between active and latent infection are used (i.e. nested PCR of serum), but only a minority (about 30%) of patients have a reactivated infection at any one time. Studies have consistently found defects in the natural killer cell functioning, which plays a critical role in controlling herpesvirus infections (indeed, patients who completely lack natural killer cells often die at a young age from herpesvirus infections), and in the 2-5A synthetase/Rnase-L pathway downstream of interferon. These are very primitive mechanisms of immune regulation found in all mammals. These innate immune mechanisms show senescence with age, which would explain why CFS is more likely to develop in the middle-aged than in the young. I would disagree that it develops exclusively in middle-aged women. For example, Laura Hillenbrand has been disabled since age 19. A recent study from the UK found that CFS was among the largest causes of prolonged school absences in teenagers. The female predominance becomes less pronounced when more stringent case definitions are applied. It is unclear why women are more likely to develop CFS, but there are many immune-mediated disorders with a 4-1 female predominance.

    As for the observation with EBV.. it is widely known that most people are exposed to EBV in the teens. As with chickenpox, it is a more serious infection when it is acquired as an adult. A minority of people will come down with acute infectious mononucleosis in their 30s and 40s. The clinical syndrome in this age group is likely to be more severe than in teens. The Dubbo study found that severity of the acute infection predicted risk for CFS. Even though teens are exposed to mono at a much greater rate, they are less likely to experience a severe illness than a middle-aged person who acquires mono later than is typical.

    Prospective cohort studies have demonstrated that CFS can follow the following serious infections: EBV, Ross River virus, Q-fever, Lyme, SARS, Girardia Lambia, Parvovirus B-19, but not the common cold or flu. This does not mean that all cases follow a serious infection, but it is suggestive that CFS patients do fine until their immune systems face an unusual challenge.

    I agree with In Vitro that it is not clear whether patients are “completely” healthy before encountering the triggering infection. I am not sure what study design could address this. It would be very expensive. Since we know there is a genetic component, one strategy would be to prospectively follow second and third degree relatives of CFS cases who believe themselves to be “healthy” and see if they have more symptoms, functional difficulties, frequent infections, or immune defects than a control group that has no CFS family history. It may be the case that some of these predisposed individuals are “slightly” sicker than average throughout their lives, and will only develop CFS and the illness identity once they are exposed to an unusual challenge that results in an increased pathogen burden.

  • Crow (UK)

    I have had CFS/ME for 2.5 years. I got it following the second of three Hep B jags. Within 24 hrs of the second jag I had very strong flu-like symptoms, which I have never recovered from. The simplest task (shower) floors me for days. Having read hundreds of research papers, listened to the retoric & debate, I am fairly certain that the problem does NOT lie with any one or two viruses……

    Could it be that ANY virus, entering the system of someone who has an already weakened immune system, caused by perhaps…….

    1) a genetic predisposition to a weak immune response?…….and/or
    2) a prolonged period of chronic stress, the hormones of which can attack the immune system (e.g. Cortisol)?

    People who are stressed produce excessive amounts of Cortisol which, when in the body for longer than is natural, actually damage the body in many ways. One of which is the immune system – and that’s why people who are stressed get all sorts of illnesses (colds, flu, food poisoning, etc). If they then get a viral infection, or an immune system triggering inoculation, or any other challenge to the immune system, they may not be able to recover from the damage that is done.

    Chronic Stress Hormones + a viral infection = CFS OR
    Genetically weak immune system + viral infection – CFS

    Or maybe all three occur in the 25% who are most severely affected? By the time the symptoms become bad enough to go to a Doctor, you will have taken time off work (lower stress hormones) and perhaps recovered from the initial viral infection – no identifiable blood markers present.

    It’s just an idea, but it seems very plausible to me at present – and for some long time now.

    Great article though. I am so grateful that there are calm, intelligent, people who are trying to progress knowledge about this illness. All power to your elbow, and your petri dishes.

  • Alex Young aka alex3619

    A very recent paper on a follow-up to the Dubbo study, has identified potential polymorphisms associated with specific symptoms. This has relevance to why we have symptom diversity as well.

    http://www.sciencedirect.com/science/article/pii/S0889159111006106

  • John Bochenek

    There are some contributors to the discussion of CFS that only want to consider what has been proven by science and medicine. Unfortunately for patients experiencing this illness, that leaves a rather nebulous mess that suggests few productive and proactive steps toward health. While it is appropriate (and necessary) for the world of medicine to rely on hard scientific data, it is also appropriate for patients to act on the best available information. This same situation unfolded in the early days of HIV, patients were forced to take self-help measures prior to the billions in research that provided a sound medical path. While time-wise CFS history is not in its early stages, research-wise it is in its infancy.

    As a CFS patient, I often ask one question to end a medical appointment: “If you were in my shoes and wanted to get your life back, what would you do next?” It produces some interesting answers that may yield a direction, and allows the doctor to step slightly beyond the medical proof that is on the table.

  • Alex Young aka alex3619

    I suspect that for many drugs and therapies that are applied to ME patients there is a huge gap between the evidence base and actual results. Patients often respond far differently to the norm, especially for drugs that involve serotonin or vasoregulation chemistry. Similarly many of the CFS studies are a mixture of psychiatric fatigue, idiopathic fatigue, PVFS and ME. In addition, using the ICC ME severity scale, most patients in such studies are mild patients, with maybe a few moderate patients thrown in. I am at the severe end of moderate but could not get into a local study due to the issues that only moderate ME cause, particularly with capacity to travel. So there is almost NO evidence base at all for severe and very severe ME patients, and very little of relevance to moderate patients. So when someone says a treatment is based on “evidence based medicine” what they mean is they are using evidence that applies to someone else if you are moderate or worse.

    As a result most doctors are experimenting on ME patients with every therapy. Patients are also experimenting on themselves. This is due to the severe underfunding of quality science over many decades. This experimentation appliesto “evidence” based approaches as much as others, perhaps more so since they have an unvalidated standard of evidence.

  • DJ

    @ doubters: Outside of all the specific medical descriptions, what is most clear is “you have never had it” End of story. I have a somewhat medical background and a psychological background and being “inside” the brain and body of someone whose system has been yoyo-ed by this, if one really has whatever this is, then it is real. Our doctor in the 80′s said, “I have never seen any disease in which each of the patients uses the same adjectives to describe their states and who go through the same sequences,” and this was NOT when things were written about it, so there was no common literature anyone of us had read. So, until you “have it”, perhaps you could be a long term assistant to someone who “really has it” and learn, grow and at the same time, help someone vs. attacking what you truly do not know about. If someone doesn’t “have it”, then I am not speaking up for them and hope they can find another solution to what ails them. Good luck, Jon, may you “Live long and Prosper”, with energy and a functioning brain unlike those you toss aside. (The joke with Chronic Fatigue is” The good news about Chronic Fatigue is you don’t die. The bad news is you don’t die.” This joke didn’t come out of nothing, Jon.)

  • http://cfsmirror.blogspot.com/ In Vitro Infidelium

    JB wrote: “There are some contributors to the discussion of CFS that only want to consider what has been proven by science and medicine.”

    Science can only progress from what is ‘known’. Modern science doesn’t concern itself with what is ‘proven’, which is a legalistic notion, but what can reproducibly be observed, in that context the scientific investigaton of M.E/CFS can only progress from well described observations of the condition as it is currently described. As Professor Racaniello rightly acknowledges, CFS is “extraordinarily complex”, and that complexity makes it absolutely essential that any discussion about [M.E]/CFS which is intended to inform researchers, physicians and patients does not lose sight of what the “well described observations of the condition”, actually are. The problem of ‘short cutting’ to treatment options without reference to what has been reliably observed is hugely significant in the case of M.E/CFS because there is no certainty that any one patient or group of patients has the same underlying pathology of any other. Even where there are apparent good reports of effective treatment interventions, there can be no certainty that such interventions will be helpful or even safe in any other individual. This is certainly a very frustrating position for both physician and patients, but the only way out of it is via research which focusses on what is currently known, and extends the current knowledge by exploring outward from there. The alternative is just flailing in the dark –of course sometimes someone may get lucky, but even then the lack of effective reference to the known characteristics of the illness will often render the ‘discovery’ problematic in its development toward useful application. The CFS/XMRV saga should stand as a constant reminder as to what can happen when researchers flail in the dark

  • Pingback: AIDS and ME/CFS: stories with two different outcomes | Raising Awareness for ME/CFS

  • Justin Reilly, esq.

    Prof. Racaniello, I just wanted to thank you for this very nice and on-point piece and also for responding to my questions on TWiV podcast. I’ve got to go now, but will be back in both places eventually to weigh in.

  • Wrong!

    This site is blocking factual information about the viruses. The negative studies failed to use clinically validated assays did not look for VP42 as found in prostate cancer or the Polytropic viruses found by Mikovits, Ruscetti, Lo and Alter. Vincent should have done more research!

  • http://washparkprophet.blogspot.com ohwilleke

    Several things make CFS epidemiology hard or discourage its prioritzation for research.

    1. CFS doesn’t reliable cause the death of the people it infects. In contrast, AIDS managed to gain such high priority despite largely afflicting people with negligible political power because for a long time an AIDS infection was a guaranteed death sentence a few years after you learned that you had it. Nothing spurs government to action like large numbers of untimely unnatural seeming deaths from untreatable diseases. In Africa, where AIDS first arose, however, government mostly just doesn’t work very well period, no matter how horrible that crisis it is called upon to deal with.

    2. CFS presents in a manner fairly easy to misdiagnose. The classic CFS story is of patients being told that they are hypocondriacs who receive inconsistent diagnosises from multiple doctors over a period of many months or years prior to an accurate diagnosis. For example, CFS presents a lot like severe unipolar depression which is much more common. In contrast, AIDS presents in an attention grabbing way that is extremely distinctive – a group of young adults in the prime of life who share the same social networks suddenly start getting diseases normally never seen in this population. Thirty somethings normally just don’t get Kaposi’s sarcoma or die of pnemonia (a characteristically geriatric disease in the modern era). Misdiagnosis was never a big problem, even before a blood test was developed, for people with full blown AIDS. This is a very different story from that of AIDS in Africa, where it first arose, large number of adults in the prime of their lives die of all sorts of infectious diseases that are barely even discussed in Western medical school textbooks.

    3. CFS has causes that somehow or other arise from very pedestrian and unremarkable circumstances. Whatever causes it involves something that isn’t very demographically distinctive and isn’t a very notable event in the memories of people who suffer from it once it manifests. In contrast, while HIV has a long latency period, gay men and IV drug users are relatively distinctive demographically and having sex with someone or using IV drugs is a memorable enough event that you recall that experience many years later when you start showing AIDS symptoms and the epidemiologist starts coming to your door asking questions. You would have to be a pretty oblivious doctor to not notice that a large share of the young men walking into your office with diseases that young adult men just don’t normally get happen to be gay, or show signs of drug addiction. This is a very different story from AIDS in Africa, where it first arose, where AIDS is not nearly so demographically distinctive.

    In short, the CDC have some very legitimate reasons for having less success in addressing CFS than it did in addressing AIDS. A better analogy would be MS or Lupus, whose cause is also unsolved, despite the fact that it is harder for an even halfway competent doctor to misdiagnose, despite the fact that the disease itself is more deadly, and despite the fact that far more money has been devoted to trying to find a cure.

    Also, lots of diseases (e.g. influenza and the common cold) have a transmission vector that is for all practical purposes impossible to interrupt without bringing the entire country to a screeching halt in near quarantine for months (as was done during the Spanish flu epidemic), and anti-viral treatments remain far less effective at curing viral infections once someone has them than antibiotics are at treating bacterial infections and that other treatments are at treating a wide variety of parasitic infections. Like chemotherapy for cancer, anti-virals are a sometimes thing that doesn’t necessary work with unrelenting reliability to the point of a full remission. Vaccines are pretty much the only game in town to deploy against diseases with ubiquitous vectors of transmission, and developing effective vaccines can be a challenge even for very well understood viruses like those that cause the flu, particularly when the epidemiological challenge is great and the disease may have an autoimmune component. None of the viruses commonly vaccinated against today are autoimmune diseases, which it looks like CFS might very well be. One can forgive the CDC for devoting fewer resources to a disease that nobody has a good game plan to deal with at list point even if they could figure out its cause.

  • Marie

    In 1992, I contracted a flu like illness that spread to my brain, my life was never the same after that. I was in the hospital for more than 2 weeks. I have been tested for just about everthing, I did test positive for HTLV II, herpesviruses, Parvo19,& EBV. Before I contracted this illness I was working 65 to 70 hours a week at a job I loved, and another 20 hours a week at home. I know what the feeling of being tired from hard work is like, this “tiredness” from CFS is way beyond that. I have never recovered. It is nearly impossible to find a doctor who will believe you, and those that do have little or nothing to offer. The CDC’s behavior is apalling. I wouln’t wish this illness on my worst ememy. That person “Jon” should refrain from stating something that is an outright lie. This is definitely an illness.

  • http://discover Tc

    the problem with CFS is it is NOT one disease. A majority probably have an autoimmune response after an unresolved viral infection.
    But there are some people who have chronic malnutrition–which may not be detectable by bloodwork. Some others have undiagnosed and untreated chronic depression, or sleep apnea. Because some individuals refuse to recognize the role proper nutrition and exercise in well being and others do not want to accept they have need of mood regulators, we may never find the origins, cures or acceptance of SFS.

  • Nancy

    It is important to remember that not everyone with active HIV developed PCP and/or Kaposi’s sarcoma. Robert Gallo ( Virus Hunting: AIDS, Cancer,& the Human Retrovirus) points out the tremendous variability of the health issues (which varies with region) caused by HTLV. “… C.
    Joseph Gibbs, have indicated that the frequency of HTLV neurological disease relative to HTLV
    leukemia varies according to region.” This suggests that genetic factors could predispose an individual to either neurological disease or leukemia.
    We patients must realize that we are all speculating about this disorder. Only good research will provide the correct answers.

  • DLT

    I had or have the DISEASE that causes CFS. It was a sudden and severe onset in my central nervous system. You can’t imagine what it’s like to lose the very center of your being until you have a shock to your CNS. Six months before, my daughter had the same experience. Both of us now have the after effects of the viral infection that no one can identify. I have a compromised immune system. I once heard this syndrome referred to as HIV-negative AIDS – that’s right on.

    My experience was that the many doctors I saw, including the folks at the Great Mayo, just didn’t want to look for anything they didn’t already know about. Even an infectious disease doctor I saw was angered that I would ask for tests – “What test’s! Do you realize how many viruses there are?!” I believe Elaine DeFreitas saw the beast early on but couldn’t get anyone to listen, especially her boss.

    I was pretty heartless toward my daughter. I had no idea what she was experiencing. I remember her lying on her bed, arms and legs stiff, fear in her eyes and I just thinking it will pass soon. Jon, may God bless you with a personal understanding like I have. Yeah, it doesn’t kill ya, but a ruined life is worse than most people think it is. Imagination. I couldn’t have imagined. no, no way.

  • Nancy

    I was reminded that back before the mycobacterium that causes tuberculosis was discovered, sick patients were told they were harboring anger, harmful emotions and this was the cause of their illness.
    Same deal for stomach ulcers. Doctors were so sure that ulcers were caused by stress that Barry Marshal
    was practically laughed off the stage at conferences. So, let’s hope the researchers just keep looking for
    some ‘stealth’ organism.

  • GKGK

    Dr. Racaniello, I’m sorry to say that I think this is one of your weakest posts; maybe your weakest ever. It is entirely based on a huge assumption: that ME/CFS has a viral cause, or is related to viral infection in some way. It is a huge assumption. Your title should be “A Tale of a Virus and an Unknown” or something like that. I think almost all of the differences in history can be explained by the fact that HIV was quickly and accurately identified as the cause of AIDS. No virus has ever been identified as the cause of ME/CFS. Indeed, if 20+ years of research as taught us anything, it is that there is no viral cause of ME/CFS; certainly none has been found. Something that happened in AIDS in 2 years, has not happened in ME/CFS in 20+ years. At some point, absence of evidence should become evidence of absence. I think we are years past that in ME/CFS. But the politics of the disease drives a sort of “Zombie Science” where viruses must be looked for over and over and over and over, etc. Scientists who research other areas are met with pitchforks and ethical complaints.

    Your evidence of virus, as far as I can see, is these two sentences: “However, there is plausible evidence for an infectious etiology, including observations that the disease is known to occur in outbreaks. Furthermore, in many cases the onset of symptoms appears to begin with a flu-like illness. ” However, all types of hysteria are commonly found in outbreaks! From the Salem Witch Trials to the recent school in NY. As for the starting with a flu-like disease, the timescale is so variable, and the research so sparse, I don’t think it is reasonable to base a theory of virus on that, when decades of search for a virus has not found one.

    GKGK

  • Dr Snow

    @GKGK

    What scientific evidence are you presenting for the Salem Witch trials? Words?

    Decades of research didn’t find HTLV-1, HIV -1 or HIV-2. It also didn’t find XMRV or other MLV-related viruses. You reasoning has no logic.

  • Paul

    I first got sick when I was ten or eleven years old. I had a couple of polio vaccines around that time. 53 years later I am still sick, although I have had many spontaneous and inexplicable remissions. It appears spontaneously and it disappears spontaneously. Remission is a true story.

    What I have is crippling when the episode reaches the bottom of the cycle. The muscles have no energy to move my body without conscious exertion, and so everything is a struggle. Getting in or out of a chair is usually a struggle. Why am I better off than having had polio?

    Then there are phases of the episode that allow me to appear in public and appear to be well when really I’m falling apart while still able to shop for food or do other simple tasks. Everybody then just assumes I’m well again. I even laugh at times, and show micro-bursts of energy. This is very misleading to people. What can I do though? I want to live. Living means laughing doesn’t it? I can’t laugh in front of people or they’ll think I’m lying or deluded about being sick.

    What I have makes me feel like I have a viral infection. I know viral infections. I used to be serially ill with head colds and flu like infections. Each episode was infused with and extended by a peculiar exhaustion and malaise lasting weeks. I would finally recover to normalcy but then I’d get another head cold and repeat the entire ordeal. This went on serially for 30 years with only rare and short breaks in between. Finally that phase ended in my forties. Now I never get colds – I have this never ending thing that feels like the malaise associated with the colds. I live for remissions but they are unpredictable and seem to not be connected with my diet or exercise or bed time or stress or lack of stress. Nothing makes sense. It’s a total enigma.

  • M.Davis

    I have had M.E. for 5 years now and believe it to be viral – undoubtedly. What strikes me most about reading the responses of other sufferers, is how reasonable we all are!! We write intelligently and politely for the most part, about our suffering and the lack of biological research being done. When really all we want to do is shout and scream about how damn ill we are but obviously we can’t because then we would be accused of being ‘mad’ and the likes of Wessely et al. would be rubbing their slimy hands with glee.
    M.E. has taught me so much. I have the wisdom of a 90 year old at the age of 37. If we ever make some sort of recovery from this illness, we will be (more than) twice the people we were before. I just hope that some smart ass scientist hurries up and gets to the bottom of this all, so that I can go back out into the world and use what I have learned, to do some good for others.

  • Lisa M.

    Thank you, Dr. Racaniello, for your informative article. And thank you all for such informative replies.

    I have had CFS/ME for just over four years. Like you, my life has changed dramatically. Clearly, this syndrome/disease is complex and confusing.
    I do hold out hope that we will have answers sooner rather than later. I’m grateful for the courageous few that have tried tirelessly to take on the mysteries of this disease.

    Please remember, too, that we will most likely never be able to get away from the ingnorance of people like Jon or GKGK or even Tc. Ignorance has always been a part of the human existence.

    I wish you peace.

  • http://profiles.yahoo.com/u/J5R44RUEYN3YRRUNMWIP3X2TSE kate s

    I am wondering if mycoplasmas are the underlying form for most if not all our immune compromised outcomes. World conference on mycoplasmas in Toulouse France summer 2013

  • Mariam Baurice

    Am from south Africa…i saw this comment on positive blogs and i will love to tell everybody how my status changes to negative, and am now a living witness of it and i think its a shame on me if i don’t share this lovely story with other people infected with this deadly virus…,hiv has been ongoing in my family… i lost both parents to hiv,. and it is so much pain ive not been able to get over.. as we all know medically there is no solution to it..and medication is very expensive. So someone introduced me to a native medical practitioner in Africa. I had a job there to execute so i took time to check out on him. I showed him all my tests and results.. i was already diagnosed with hiv and it was already taking its towel on me.. i had spent thousands of dollars so i decided to try him out…i was on his dosage for 6 weeks. although i didn’t believe in it, i was just trying it out of frustration… and after 2 weeks, i went for new tests… and you wont believe that 5 different doctors confirmed it that am negative. It was like a dream,, i never believe aids has cure. Am now negative, am a living witness. I don’t know how to thank this man… i just want to help others in any way i can have joined many forums and have posted this testimonies and alot of people has mail and called this man on phone and after 2 months they all confirmed negative..bbc news took it live and every.. hope he helps you out.. everybody saw it and its now out in papers and magazines that there’s native cure for hiv and all with the help of this man,,have tried my own parts and all left with you,,if you like take it or not..god knows have tried my best. About 97 people have been confirmed negative through me..and they send mails to thanks me after they have been confirmed negative, this man is real. Don’t miss this chance,,hiv is a deadly virus, get rid of it now.. DR.ABEGBESPELLHOME@HOTMAIL.COM or call +2347067167955

  • Monique Remmelzwaal

    I am a proven case that viruses caused ME/CVS.

    I had viral meningo radiculitis (a severe form of meningitis) in 2002 and was hospitalised. A few month before that, antibodies for Epstein-Barr virus were found in my blood.

    I didn’t recover from this and was diagnosed with M.E. Still am.

    My experience is that viruses sometimes can go through the brain barriere. And my suggestion to scientists is to not only check the blood, but especially the SPINAL FLUID!!! In this fluid, which runs through the brain, stuff can be found that affects the brain and nervous system. ME/CVS covers both virology and neurology, scientist have to start working together.

    Best to test the brain fluid during an outbreak, when symptoms are most severe. (e.g. I get much more ill when herpes show up on my lip, it affects the whole system.)

    Hoping for a recovery!!!! (also for my sweet sister who got ill the same time as me).

    As Vincent Racaniello says ‘this disease is extraordinarily complex. But that never stopped a good scientist.’

  • Bruno Rico

    Hello let me give this testimony to the public about a great man who help me out in serious illness. I had HIV AID for good 5year and I was almost going to the end of my life due to the way my skin look like all I have in my mind is let me just give up because life was not interested to me any longer but I just pray for God every day to accept my soul whenever I’m gone lucky to me my kid sister ran to me that she found a doctor in the internet who can cure HIV/AIDS she helped me out on everything the man ask for my picture, so he can cast a spell on me from his temple after all he ask is done 45mins later I started getting more stronger my blood started flowing normally for 4 to 5 days I start getting Weight before a month my body start developing my skin start coming up after 2month I went for HIV test and I was tested negative I’m so happy that I can say I’m not a HIV patient if you have HIV/AIDS or any sickness please for your sake contact him for cure now on his email address: greatgumblaspellhome@outlook.com and i pray that he will help you also.All thanks to DR.GUMBALA, you can also contact me via email address: greatgumblaspellhome@outlook.com

  • Cynthia David

    am from uk am here to give my testimony about how i got my hiv disease and how i flew it quickly after having trust on my spell doctor who cured me immediately .since the year i married to the man i didnt love because my parents false me to marry him.i have been enjoying relationship and sex life with him .he do spend time on work and dont have time for me . sometime he do sleep at his work and also do carry women because he has the money to spend but doesnt spend it on me . so i was so jealous to the extent that i cant control my anger and i decided to start cheating on him with exboyfriend . because my husband donot always be at home except on weeend .i have sex with him without protection .after somemonths been in love with my exboyfriend i was so sick and decided to go have a test and i found i was hiv positive . i feel so sad and i was ashamed because i didnt now how to open up to my husband i hate before my exboyfriend denied me and when my husband found out about what wads going on he devoirced me and i was ill for good 3years i went to many places for solution but there was no solution . so one day i was asing GOOGLE some question on how i can get a cure and how i can get somemedication which i will be taking to my own suprise they brought one email out named drozallaspellhome@outlook.com that this powerful man can cure hiv i didnt believe about the cure before but i toke the email and search it on GOOGLE and found many good testimonies about him people have been giving more testimonies about him so i contacted him about my situation . he told me all the procedures which i will take and i did before i knew what was happening he called me and told me to go for an hiv test which i did and when the result was out i was hiv negative .thanks to drozallaspellhome now as i am giving this testimony am fully settled down with my husband now and we love ourselves .i give this testimony for people around that was in my shoes so that they can also be cured like me .so if you also need a solution also you can email him at drozallaspellhome@outlook.com

  • brotherhood temple

    I want to use this medium to tell the world about dralabokun who helped
    me in getting my lover back with his powerful spell, my ex and i where
    having misunderstanding which led to our breakup though i went to beg
    her several times to please forgive and accept me back because i know i
    offended her but each time i went i always feel more deeply in pain and
    agony because she always walk out on me and would not want to listen to
    what i have to tell but on i faithful day as i was browsing i came arose
    a testimony of a woman whose problem was more than mine and yet
    dralabokun helped her with his spell so i was happy and also contacted
    dralabokun for help via email and then told him my story but the only
    thing he said was that i will wipe your tear with my spell so lucky for
    me everything want well just as he promised and right now i have got my
    fiance back and we are both living happily. there is nothing dralabokun
    can not do with is spell and just as promise my self i will keep
    testifying on the internet of how dralabokun helped me.Are your problem
    greater that mine or less i give you 100% guarantee that dralabokun will
    put an end to it with his powerful spell, contact dralabokun for help
    Via email dralabokun@gmail.com or contact +2348071145063

    HIV/AID CURE
    1. GETTING YOUR EX LOVER BACK.
    2. WINNING LOTTERIES.
    3. CHILD BEARING.
    4. BREAKING OF GENERATION COURSE.
    5. GETTING OF JOB.
    6. JOB PROMOTION.
    7. MONEY SPELL.
    8. SPIRITUAL PROTECTION.

    9. HERBAL CARE.
    io hiv aid cure
    10. BEAUTY SPELL.

  • Katherina

    I am from Mexico, i had HIV AIDS for three years, i also gave birth to my first with HIV, i was in deep sorrow and in search for help on how to treat myself, one day i came across a blog where a testimony was given by woman Named SARA who was treated from HIV AIDS by the help of spell caster, so i made a contact to the email address dr.OLOKUM i got from the blog, i never really believed but i just decided to give it a try, this spell caster Dr OLOKUM told me everything i needed to know and what to do to get cured, so i made an arrangement for the treatment i applied the medicine and after 5 days, i was feeling good and healthy at once, my strength was regained i went for check up in the hospital and my doctor told me i am cured, this is the greatest miracle that has happened to me in my whole life, and that is why i am sharing my testimony to the world, i never expected this was possible, if you have any health issue call +2347053977842 or email him for help LAVENDERLOVESPELL@YAHOO.COM

  • John Park

    Good morning everyone, my name isrobert sandra from USA, I have been suffering from

    HIV/Aids for over 4years now, and suddenly, i have spent all my money all to make sure

    i get healthy all day, but happily, last month January 12th 2013, I came in contact

    with a traditional doctor also known as a chief priest on a newspaper who is called Dr

    alabokun who has help much people to cure their aids disease, firstly i taught it was a

    joke until i contacted him dralabokun@gmail.com and he said that if i am ready

    for this work, i told him yes, and he collected my details and told me that after he

    has finished consulting his oracle he will run back to me on when to go for a medical

    check up, i was unhealthy ling surprise. And truly last week Monday Dralabokun called me

    to quickly go for a medical checkup, which I did, only to find out that I was not with

    any HIV disease anymore, my friends and families who left me before run back to me. I

    now found out that God in Heaven is using this man to bless and heal us all, he is a

    great and powerful man, again I say to you sir, that God Almighty will uplift you and

    your great work you did for I and other people. Please i will sincerely advice all HIV

    patient to contact this great powerful man called Dr alabokun for your solutions now dralabokun@gmail.com he will help you on your HIV

    problems…contact +2348071145063

  • John Park

    t hanks to Dr.alabokun for his good work I really believe HIV have cure I was
    HIV positive over since 1year plus before I come across a comment
    dr.alabokun that he have cure to any disease and virus but when I saw it
    i have it in mind that he can’t cure HIV I just decided to give a try I
    contact him that night lucky to me he said yes but I don’t believe him I
    think it was a scam or some thing like that but I still hold on to see
    the work of dr.alabokun if he is saying the true he ask for different
    things and some question about me I give him all the detail he needed
    and I wait to see his reply to my problem all the things is done he ask
    me to go for check up I went for hiv test I cant believe I was negative
    the medical doctor was surprise and doctor even ask for dr alabokun
    email which i give to him, he he is help people that contact him also he
    can still help you on your cure thanks Dr.alabokun for helping me for
    the cure at this young age if you need help contact him now dralabokun@gmail.com or contact +2348071145063

  • bella mark

    ALL THANKS BE TO THIS GREAT SPELL CASTER THAT HELP ME CURE MY HIV,THANKS ONCE AGIAN.

    Do you believe HIV have cure if yes meet a man who cure HIV aids for 45mins
    spell, I was HIV positive for 5year and I was in a serious illness but him
    the great man save my life he is the greatest of almost all spell caster
    thanks DR.UDO native of UDO the man that lord sent to help all HIV
    patients thank for curing my virus. if you need his help contact him for
    great and happy life my friends, To get this powerful healer full article
    and trust on his origination and references please visit him now again at:
    email: DR. iziengbeayalovespell@gmail.com

  • wandy shehi

    MERCY ANTHONY, i want to give almighty praise to Dr OLUWA who help me

    to cure my HIV/AID, please help me to give thanks to him he is a great
    man who God send from heaven to save people’s life, when i contacted
    this deadly virus i thought that was the end of the world for me little
    did i know that there is a man called DR OLUWA OF AFRICA who has made a

    breakthrough in the cure of HIV and cancer cure with herbs when i
    confided in a friend here in south Africa he told me about this man
    called DR OLUWA and how he cured the mum and dad of HIV after two
    years
    of living with this deadly diseases he told me of the cost and procedure
    i felt it was worth a try after i have been spending so much in the
    drugs to make me live like every normal human being so i contacted DR
    ADIZER and did as he commanded without missing words he did all he
    needed
    to do and sent me the herbs here in south Africa i took it as he
    directed it was exactly seven days as DR OLUWA has spoken when he
    emailed
    me and told me to go for a check up again and i went to my greatest
    surprise it was negative i felt it was a dream so i went to three
    different hospital and it was still negative then i cried out in a loud
    voice and people gathered in the hospital and i told them my story in
    tears how this man called DR OLUWA have saved my life and they started
    demanding for his mail to contact him it was only last week my friend
    Vanessa who was HIV positive came back from visiting DR OLUWA as a
    healthy woman i told her about DR OLUWA you can reach him through his
    emai address oluwahivherbalcure@gmail.com
    OR 08050354815he never fails hold on my friend dont cry no more when our helper is here i
    believe in him he am sure you will be lucky as i am too just email him
    on oluwahivherbalcure@gmail.com

    OR +2348050354815 he is a savior of life

  • Amanda Philip

    Hello!! I’m indeed very happy for the great help that Dr. Oraede rendered to me, I was a HIV patient my husband also was a HIV patient, we saw a blog whereby Dr. Oraede cured HIV, we (Me and My Husband) decided to contact him which we did, he asked us to buy some items, unfailingly we sent him the money he will need in buying the items required, He casted the spell and asked us to go for check-up after three days of casting the spell, Luckily for us we were tested HIV negative, now I believe all these Testimonies about him on the internet, he is truly a great man, if you want to discuss with me on how he cured us, kindly email me on philipamanda45@gmail.com or you can contact the great Herbalist and a spell caster on dr.oraedespellhome@hotmail.com dr.oraedespellhome@gmail.com or you can call him via his mobile phone number on +2349038604218

  • Amanda Philip

    Hello!! I’m indeed very happy for the great help that Dr. Oraede rendered to me, I was a HIV patient my husband also was a HIV patient, we saw a blog whereby Dr. Oraede cured HIV, we (Me and My Husband) decided to contact him which we did, he asked us to buy some items, unfailingly we sent him the money he will need in buying the items required, He casted the spell and asked us to go for check-up after three days of casting the spell, Luckily for us we were tested HIV negative, now I believe all these Testimonies about him on the internet, he is truly a great man, if you want to discuss with me on how he cured us, kindly email me on philipamanda45@gmail.com or you can contact the great Herbalist and a spell caster on dr.oraedespellhome@hotmail.com dr.oraedespellhome@gmail.com or you can call him via his mobile phone number on +2349038604218…..

  • DENIE

    Dr. Lawrence God will continue to bless you more abundantly, for the good works you are doing in peoples life, I will keep on writing and posting testimonies about you on the Internet, I’m Helen Tolbert, I was a HIV patient, I saw a blog on how Dr. Lawrence cured someone, I contacted him and also got my healing, kindly email him now on drlawrencespelltemple@gmail.com or call him +2348143988536

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