Lipkin And Horning Draw A Blank

From the tweets from the 2014 "Stanford ME/CFS Symposium" I can see that Lipkin focuses on the "microbiome" (aka all the "good" and "bad" bacteria that live in your gut).

While he does not say it explicitly, he found no prevalent infections nor any prevalent immune system problems in people with ME/CFS. Granted, he found some leads with regards to IL-17 and eotoxins – but I am cautious and don't expect that anything will come from this.

And while I think that there is possibly a connection to the gut (and to nutrition!) in many diseases, I however think the reason that Lipkin looks in the gut is because he has exhausted the paths of inquiry that involve the body "proper".

Furthermore Lipkin appears to think that ME/CFS is one "monolithic" disease, so the only place where this one disease must hide (in his view) is in the microbiome in the gut.

I think he is wrong on two accounts:

1. I think there is good evidence that ME/CFS is not one monolithic disease, but instead a set of symptoms that can be caused by several diseases.

2. Lipkin is – as so many in medical research and the medical profession – unaware of the pathogenic potential of some the foods we eat (with dairy, cereal grains and seed oils/PUFA/TFA in my mind being probably the prime suspects).

For me, this is the disenchantment of Lipkin, as I had some hope that he might be able find at least one prevalent disease in people with ME/CFS.

(And BTW some of the things he said on "Autism and GI complains", on "Kawasaki syndrome and candida in the troposphere" and on "Chronic Lyme" are borderline woo. I do not think that Lipkin is a good ally. However if he investigates these things properly, and then clearly announces if he draws a blank, then I am OK with his lines of inquiry. The problem starts when he does not clearly say when he draws a blank…)

Personally I don't expect that Lipkin/Horning will find anything useful in the gut/microbiome – but it is good that they continue their inquiry, if only that they might spread more awareness of the disease or might find something by a lucky coincidence. One never knows…

[Postscript] One other thing is noteworthy: Lipkin found no evidence whatsoever that ME/CFS is caused by HHV-6 / HHV-6B. He found 3 or 4 patients – out of 586(!) – with HHV-6 or HHV-6B. This more or less invalidates the entire argument by the HHV proponents that ME/CFS is caused by an ongoing HHV infection. I think especially the attention given to Montoya (and others) in that regards is not warranted.

[Postscript 2] One more thing: As Lipkin didn't explicitly say it, let me put it in clear words:

Lipkin found no evidence for an ongoing infection in people with ME/CFS.

Clear enough for you?

If ME/CFS is caused* by pathogens (viruses or possibly bacteria), then they are long gone after the initial acute infection**. A case of "hit and run", if you want – the pathogen is gone, the damage stays.

No need to treat a pathogen that is gone, as that will usually do more harm than good. Or as they say at NASA:

Things are never so bad that they can't be made worse.

So the first order of business: Don't make things worse. Anti-viral and anti-bacterial and anti-whatnot medications have a high potential to make things worse – best to use them only if you are really really sure.

So, if there is no pathogen, what can you do? The best one could do is to identify the damage, and try to treat it (e.g. orthostatic intolerance with medication targeting the blood preasure – speak with your doctor!). If there is anything that alleviates symptoms, then doing it might be a good ides. Change nutrition, try a Paleo Diet, try an Eleminaion Diet. But please, stop claiming that phantom ME/CFS viruses, and phantom ME/CFS bacteria, and phantom ME/CFS fungi supposedly hide in the gut of people with ME/CFS, or in their tissues, or god knows where – you are hurting yourself and hurting other people.

PLEASE. STOP. IT.

Please?

--
* There seems however to be evidence to indicate that acute infections can cause ME/CFS in some cases.

** Unless you are one of those rare 1 in a 100 ME/CFS cases were it is clearly established that there is an ongoing infection – and no, "Chronic Lyme" is not a ongoing infection, and neither is "Candida", nor "Chlamydophila pneumoniae" or any other somesuch woo terms being peddled by people who don't know better. These are makebelieve terms that only fool people (including those who doctors who use these terms).

How common is HSV-1?

HSV-1, famous for causing cold-sores, seems to be very common:

A 2006 study found evidence of HSV-1 infection in 57.7 percent of American adults, ages 14 to 49. Bryan Cullen, a virologist at Duke University, told me he's seen studies showing that closer to 70 percent of adults are infected — although only something like 1/3rd of those will ever get cold sores.

(via boingboing.net/2013/01/24/fun-science-fact-anne-of-gree.html)

HSV-2, the main cause of genital herpes, on the other hand seems to be much less common, as HSV-2 is sexually transmitted – while HSV-1 is transmitted through normal contact between family members. Less than a fifth of the population seem to have HSV-2, with a sinking number of people are being infected it seems.

Post-Mono can look like CFS - An Follow-Up

A follow-up to this:

Chronic fatigue syndrome following infections in adolescents

Katz BZ, Jason LA.

Abstract

PURPOSE OF REVIEW:
To review the recent epidemiology, pathophysiology, and treatment of postinfectious chronic fatigue syndrome (CFS) in adolescents.

RECENT FINDINGS:
Thirteen percent of adolescents (mainly women) met the criteria for CFS 6 months following infectious mononucleosis; the figure was 7% at 12 months and 4% at 24 months.

Peak work capacity, activity level, orthostatic intolerance, salivary cortisol, and natural killer cell number and function were similar between adolescents with CFS following infectious mononucleosis and recovered controls.

Autonomic system, oxygen consumption, peak oxygen pulse, psychological and cytokine network differences were documented between those who recovered and those who did not.

SUMMARY:
The prognosis of CFS is better in adolescents than in adults.

Activity level, exercise tolerance, and orthostatic testing could not distinguish patients with CFS from adolescents who have recovered from infectious mononucleosis (controls), while certain cytokine network analyses, life stress factors, and autonomic symptoms could.

Via Adrienne Dellwo

… Looking at post-mono adolescents, researchers found it was mainly the girls who continued to have symptoms long term.

Many of those who fit the ME/CFS diagnostic criteria early on no longer did at follow up.

Here's at look at how the length of time post-infection effected the diagnostic rate:

6 months: 13%
12 months: 7%
24 months: 4%

Researchers say the following factors distinguished those with ME/CFS from kids who'd fully recovered:
- Certain cytokine network test results
- Oxygen consumption, at rest and during exercise
- Life stress factors (such as those caused by long-term illness)
- Symptoms of autonomic nervous system dysfunction

They did not find significant differences in activity level, exercise tolerance or orthostatic testing.
…

Post-Mono can look like CFS

CFIDS in 2009: Post-Mono CFS in Teen Girls

Ben Z. Katz, M.D., of Northwestern University has just published results from a study of teens who were followed for two years after the onset of acute infection with Epstein-Barr virus (mononucleosis). The article is published in the July 2009 issue of Pediatrics. Criteria for CFS were met by 13 percent of adolescents at 6 months after acute infection. Seven percent remained ill at 12 months, and 4 percent met CFS criteria at 24 months. With time, most adolescents recovered. Only 2 adolescents with CFS at 24 months seemed to have recovered or had an explanation for CFS at 12 months, but then were reclassified as having CFS at 24 months.

All 13 adolescents who had CFS 24 months after onset of mononucleosis were girls. Compared with those who did not have CFS at 24 months, they reported greater fatigue severity at 12 months. Corticosteroid treatment during the acute phase of mononucleosis was not associated with an increased risk for the development of CFS.

This study was funded by NIH and its principal investigator is Renee Taylor, PhD, at University of Illinois-Chicago. Dr. Katz and Dr. Taylor are also collaborating with Association-funded researcher Gordon Broderick, PhD, who is studying the same patient group to understand differences between those who recovered from mono and those who remained ill at various time points. Read more about the Association's study at http://www.cfids.org/cfidslink/2009/030402.pdf.

An article about the study was circulated by Reuters and can be read at http://www.vancouversun.com/health/Mono+linked+chronic+fatigue+syndrome+teens/1817020/story.html.

Medscape News also reported on the publication at http://www.medscape.com/viewarticle/705653. You can also find continuing education courses about CFS on Medscape to share with your healthcare professional, including the one sponsored by the CFIDS Association of America that has attracted more than 243,000 page views since it went live in October 2008. The CFS course is located at http://cme.medscape.com/viewprogram/17442.

Journal citation: “Chronic fatigue syndrome after infectious mononucleosis in adolescents.” Katz BZ, Shiraishi Y, Mears CJ, Binns HJ, Taylor R. Department of Pediatrics, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine and Children's Memorial Hospital, Chicago, Illinois 60614, USA. Pediatrics. 2009 Jul;124(1):189-93.

Daft Idiots

Ohio State University press release.

Discovery Could Lead to Faster Diagnosis For Some Chronic Fatigue Syndrome Cases

COLUMBUS, Ohio - For the first time, researchers have landed on a potential diagnostic method to identify at least a subset of patients with chronic fatigue syndrome (CFS), a complex disorder with no known definitive cause or cure.

In a pilot study of six patients, scientists detected specific antibodies linked to latent Epstein-Barr virus reactivation in blood samples from people who had experienced classic CFS symptoms and responded to antiviral treatment. Control blood samples from 20 healthy people showed no such antibodies.

…

So they tested six(!) patients, and on that basis the claim to have identified "at least a subset of patients with chronic fatigue syndrome (CFS)". One does not need to read any further.

m(

And no only that, but "for the first time", none the less.

If anybody has identified subsets in CFS, it was Kathleen and Alan Light – long ago, with a much larger base of patients.

So who are these daft idiots, which lend their names to such BS?

Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset

A. Martin Lerner, Maria E. Ariza, Marshall Williams, Leonard Jason, Safedin Beqaj, James T. Fitzgerald, Stanley Lemeshow, Ronald Glaser

Martin Lerner and Leonard Jason – guess my moderately elevated opinion of these two jokers just evaporated. While Lerner seemed a bit suspicious to me, Jason did not appear like someone who would participate in such publicity stunts – oh well.

Maybe, just maybe, these results will hold up in a larger study – or maybe it goes the way of all Herpesviridae results in ME/CFS (I'm looking at you Jose Montoya).

Study "No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome"

A negative HHV-6 study from Bethesda.

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome

Peter D Burbelo, Ahmad Bayat, Jason Wagner, Thomas B Nutman, James N Baraniuk, Michael J Iadarola

National Institutes of Health, Bethesda, MD
Georgetown University, Washington, D.C.

Abstract:
Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) are associated with a variety of conditions including rash, fever, and encephalitis and may play a role in several neurological diseases.

Here luciferase immunoprecipitation systems (LIPS) was used to develop HHV-6 serologic diagnostic tests using antigens encoded by the U11 gene from HHV-6A (p100) and HHV-6B (p101).

Analysis of the antibody responses against Renilla luciferase fusions with different HHV-6B p101 fragments identified an antigenic fragment (amino acids 389 to 858) that demonstrated ~86% seropositivity in serum samples from healthy US blood donors.

Additional experiments detected a HHV-6A antigenic fragment (amino acids 751-870) that showed ~48% antibody seropositivity in samples from Mali, Africa, a known HHV-6A endemic region.

In contrast to the high levels of HHV-6A immunoreactivity seen in the African samples, testing of US blood donors with the HHV-6A p100 antigenic fragment revealed little immunoreactivity.

To potentially explore the role of HHV-6 infection in human disease, a blinded cohort of controls (n=59) and chronic fatigue syndrome (CFS) patients (n=72) from the US was examined for serum antibodies.

While only a few of the controls and CFS patients showed high level immunoreactivity with HHV-6A, a majority of both the controls and CFS patients showed significant immunoreactivity with HHV-6B.

However, no statistically significant differences in antibody levels or frequency of HHV-6A or HHV-6B infection were detected between the controls and CFS patients.

These findings highlight the utility of LIPS for exploring the seroepidemiology of HHV-6A and HHV-6B infection, but suggest that these viruses are unlikely to play a role in the pathogenesis of CFS.

Not really a particularly large CFS patient cohort in this study. Especially considering that I don't know how the CFS patients were selected, nor by whom – none of the names ring a bell for me.

While I don't think that any one of the herpes viruses is the root cause of ME/CFS, this study from Bethesda does not instill confidence for me – oh well.

Here we have researcher from Bethesda who know something about HHV-6, but I don't know if they know much about CFS patient populations. And then here we researchers from Latvia who don't seem to know much about HHV-6, but may (or may not) know more about CFS. And those who know both HHV-6 and CFS produce underwhelming results. It's a sad world.

José Montoya's new paper

Via CO-CURE:

Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein–Barr virus IgG antibody titers

Tessa Watt, Stephanie Oberfoell, Raymond Balise, Mitchell R. Lunn, Aroop K. Kar, Lindsey Merrihew, Munveer S. Bhangoo, José G. Montoya

Article first published online: 10 OCT 2012

J. Med. Virol., 84: 1967–1974. doi: 10.1002/jmv.23411

Abstract

Valganciclovir has been reported to improve physical and cognitive symptoms in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV-6) and Epstein–Barr virus (EBV) IgG antibody titers.

This study investigated whether antibody titers against HHV-6 and EBV were associated with clinical response to valganciclovir in a subset of CFS patients.

An uncontrolled, unblinded retrospective chart review was performed on 61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks).

Antibody titers were considered high if HHV-6 IgG ≥1:320, EBV viral capsid antigen (VCA) IgG ≥1:640, and EBV early antigen (EA) IgG ≥1:160.

Patients self-rated physical and cognitive functioning as a percentage of their functioning prior to illness.

Patients were categorized as responders if they experienced at least 30% improvement in physical and/or cognitive functioning.

Thirty-two patients (52%) were categorized as responders.

Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively.

Baseline antibody titers showed no significant association with response.

After treatment, the average change in physical and cognitive functioning levels for all patients was +19% and +23%, respectively (P < 0.0001).

Longer treatment was associated with improved response (P = 0.0002).

No significant difference was found between responders and non-responders among other variables analyzed.

Valganciclovir treatment, independent of the baseline antibody titers, was associated with self-rated improvement in physical and cognitive functioning for CFS patients who had positive HHV-6 and/or EBV serologies.

Longer valganciclovir treatment correlated with an improved response.

An uncontrolled, unblinded retrospective chart review? With self-rated improvement? I am seriously underwhelmed.

If you have high titers, I won't blame you if you might want to give it a shot. If someone else pays for it, or if you have the money, that is.

And don't expect any miracles and don't bankrupt yourself on Valganciclovir.

Herpes viruses seem to be a contributing factor for some people with ME/CFS, but I would be seriously surprised if it turns out to cause ME/CFS in a larger sub-group of ME/CFS.

Active HHV-6 infection associated with ME/CFS?

Association of Active Human Herpesvirus-6, -7 and Parvovirus B19 Infection with Clinical Outcomes in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Svetlana Chapenko 1
Angelika Krumina 2
Inara Logina 3
Santa Rasa 1
Maksims Chistjakovs 1
Alina Sultanova 1
Ludmila Viksna 2
Modra Murovska 1

1 August Kirchenstein Institute of Microbiology and Virology
2 Department of Infectology and Dermatology
3 Department of Neurology and Neurosurgery

All: Riga Stradins University, Riga, Latvia

Abstract

Frequency of active human herpesvirus-6, -7 (HHV-6, HHV-7) and parvovirus B19 (B19) infection/coinfection and its association with clinical course of ME/CFS was evaluated.

108 ME/CFS patients and 90 practically healthy persons were enrolled in the study.

Viral genomic sequences were detected by PCR, virus-specific antibodies and cytokine levels—by ELISA, HHV-6 variants—by restriction analysis.

Active viral infection including concurrent infection was found in 64.8% (70/108) of patients and in 13.3% (12/90) of practically healthy persons.

Increase in peripheral blood leukocyte DNA HHV-6 load as well as in proinflammatory cytokines’ levels was detected in patients during active viral infection.

Definite relationship was observed between active betaherpesvirus infection [??? betaherpesvirinae include HCMV!] and subfebrility, lymphadenopathy and malaise after exertion, and between active B19 infection and multijoint pain.

Neuropsychological disturbances were detected in all patients.

The manifestation of symptoms was of more frequent occurrence in patients with concurrent infection.

The high rate of active HHV-6, HHV-7 and B19 infection/coinfection with the simultaneous increase in plasma proinflammatory cytokines’ level as well as the association between active viral infection and distinctive types of clinical symptoms shows necessity of simultaneous study of these viral infections for identification of possible subsets of ME/CFS.

(via CO-CURE)

This seems like a reasonably large study, with 108 ME/CFS patients and 90 controls.

Might be the case that HHV-6 is involved, or it might not be the case. I'm still skeptical.

One needs to be cautious: Other countries may use the criteria differently, when translated to the local language. Doctors there might have different traditions how to diagnose, and what to diagnose. E.g. CFS seems to be unknown in France and the French-speaking part of Belgium – if you did a study about CFS in France, the results would not be trustworthy.

The abstract could have been written a lot clearer.

Why do they suddenly write about betaherpesvirinae? Neither HHV-7, nor B19 are betaherpesvirinae! And betaherpesvirinae include HCMV (HHV-5)! This is confusing.

And why did they not distinguish between HHV-6A and HHV-6B?

At least it seems that if you do not have multijoint pain, then you can ignore parvovirus B19.

PS: I am always pleased to see that clinical research still seems to be a woman's domain in the former-communist countries.

EBV in MS? Yes? No? Or maybe yes after all?

Research on the possible contribution of Epstein-Barr virus (EBV) to Multiple Sclerosis (MS) has yielded discordant results. However, a new study on EBV and MS suggests that the association may be more “sophisticated” than thought.

We will wait and see. My money is on Terry Wahls though.

Meier admits that the role of a viral agent in MS is mired in controversy. “People have tried to pinpoint trendy viruses for decades.”

Cytomegalovirus (CMV / HHV-5) involved in high blood pressure?

Originally carrying out an investigation into the gene regulatory microRNA (miRNA) expression differences between Chinese patients with and without high blood pressure, the researchers soon discovered an obvious sign of HCMV infection in the form of a virally encoded miRNA.

Quantitatively determining the miRNA levels in blood samples, many miRNAs were up or down regulated but the group focused in on one in particular: hcmv-miR-UL112 - derived from HCMV that was shown to be highly expressed in those suffering from primary hypertension. These expression differences were thought to be down to endothelial cells within the blood sample, termed circulating endothelial cells. HCMV seropositivity as well as higher amounts of viral DNA, in general, was seen to be correlated with the high blood pressure group, especially when other factors were considered. This correlation was not seen with other common human viruses (Epstein-Barr and adenoviruses) suggesting a certain specificity.

Remember: That is only a possible correlation, not a definitive causative link.