Racaniello on Picornaviruses, Enteroviruses, Polio, Coxsackie…

Vincent Racaniello has some nice information on these viruses:

And he made a very excellent lecture:

Different pathogens can cause CFS-like illness

After two studies popped up recently (Naess et al. 2012 and Morroy et al. 2012), I thought I'll collect here some of the studies implicating different pathogens. Interesting is that the finding of Hickie et al. 2006 (to paraphrase: "Initial illness severity predicts duration of chronic fatigue") was found in Morroy et al. 2012, albeit reported inversely (as paraphrased: "the majority of persons with mild illness recover spontaneously within a few weeks"). The report of David Bell on patients of the Lyndonville outbreak after 25 years seem to go in a similar direction, that those who got hit the hardest, stayed the most ill.

Some things are missing. First of all, I have no measure of the quality of most of these studies. Hickie 2006 seems solid. John Chia's finding of Enterovirus seems intriguing (and jives well with previous findings of researchers on the British Isles), yet I'm cautious. If half of the people presenting with CF(S) at John Chia's office have persistent Enterovirus infections, then Ian Lipkin will find a comparable number.

Then another thing that is missing is (Chronic) Lyme and other pathogens like Mycoplasma.

And the third thing to keep in mind is that local outbreaks can skew any numbers, as obviously an outbreak increases the number of people who have the same pathogen in that region. Giardia cases may or may not be common now in Haukland, Norway – the incidence of Giardia in CF(S) cases in e.g. California may or may not be neglectable.

So here we go:

Hickie et al. 2006: a prospective cohort study on Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis) in Australia:

Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study

Ian Hickie 1, Tracey Davenport 1, Denis Wakefield 2, Ute Vollmer-Conna 3, Barbara Cameron 2, Suzanne D Vernon 4, William C Reeves 4, Andrew Lloyd 2

Cite this as: BMJ 2006;333:575
Degenerative joint disease Drugs: CNS (not psychiatric) Epidemiologic studies

1 Brain and Mind Research Institute, Sydney University, Sydney, NSW 2050, Australia,
2 School of Medical Sciences, University of New South Wales, Sydney, NSW 2052,
3 School of Psychiatry, University of New South Wales,
4 Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 31033, USA

Correspondence to: A Lloyd

Abstract
Objective To delineate the risk factors, symptom patterns, and longitudinal course of prolonged illnesses after a variety of acute infections.

Design
Prospective cohort study following patients from the time of acute infection with Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis).

Setting
The region surrounding the township of Dubbo in rural Australia, encompassing a 200 km geographical radius and 104 400 residents.

Participants
253 patients enrolled and followed at regular intervals over 12 months by self report, structured interview, and clinical assessment.

Outcome measures
Detailed medical, psychiatric, and laboratory evaluations at six months to apply diagnostic criteria for chronic fatigue syndrome. Premorbid and intercurrent illness characteristics recorded to define risk factors for chronic fatigue syndrome. Self reported illness phenotypes compared between infective groups.

Results
Prolonged illness characterised by disabling fatigue, musculoskeletal pain, neurocognitive difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue syndrome phenotype was stereotyped and occurred at a similar incidence after each infection. The syndrome was predicted largely by the severity of the acute illness rather than by demographic, psychological, or microbiological factors.

Conclusions
A relatively uniform post-infective fatigue syndrome persists in a significant minority of patients for six months or more after clinical infection with several different viral and non-viral micro-organisms. Post-infective fatigue syndrome is a valid illness model for investigating one pathophysiological pathway to chronic fatigue syndrome.

Naess et al. 2012 on Giardia in Norway:

Chronic fatigue syndrome after Giardia enteritis: clinical characteristics, disability and long-term sickness absence.
Halvor Naess, Morten Nyland, Trygve Hausken, Inghild Follestad and Harald I Nyland

Institute of Clinical Medicine, Department of Neurology, and Unit for Gastroenterology, Department for Medicine, Haukeland University Hospital, N-5021 Bergen, Norway

BMC Gastroenterology 2012, 12:13 doi:10.1186/1471-230X-12-13

Abstract (provisional)
Background
A waterborne outbreak of Giardia lamblia gastroenteritis led to a high prevalance of long-lasting fatigue and abdominal symptoms.

The aim was to describe the clinical characteristics, disability and employmentloss in a case series of patients with Chronic Fatigue Syndrome (CFS) after the infection.

Methods
Patients who reported persistent fatigue, lowered functional capacity and sickness leave or delayed education after a large community outbreak of giardiasis enteritis in the city of Bergen, Norway were evaluated with the established Centers for Disease Control and Prevention criteria for CFS.

Fatigue was self-rated by the Fatigue Severity Scale (FSS).

Physical and mental health status and functional impairment was measured by the Medical Outcome Severity Scale-short Form-36 (SF-36).

The Hospital Anxiety and Depression Scale (HADS) was used to measure co-morbid anxiety and depression.

Inability to work or study because of fatigue was determined by sickness absence certified by a doctor.

Results
A total of 58 (60%) out of 96 patients with long-lasting post-infectious fatigue after laboratory confirmed giardiasis were diagnosed with CFS.

In all, 1262 patients had laboratory confirmed giardiasis.

At the time of referral (mean illness duration 2.7 years) 16 % reported improvement, 28 % reported no change, and 57 % reported progressive course with gradual worsening.

Mean FSS score was 6.6. A distinctive pattern of impairment was documented with the SF-36.

The physical functioning, vitality (energy/fatigue) and social functioning were especially reduced.

Long-term sickness absence from studies and work was noted in all patients.

Conclusion
After giardiasis enteritis at least 5% developed clinical characteristics and functional impairment comparable to previously described post-infectious fatigue syndrome.

Morroy et al. 2012 Q-fever (Coxiella burnetii) in The Netherlands:

Self-reported sick leave and long-term health symptoms of Q-fever patients

Gabriella Morroy 1,2, Hans H. J. Bor 2, Johan Polder 3, Jeannine L. A. Hautvast 2, Wim van der Hoek 4, Peter M. Schneeberger5 and Clementine J. Wijkmans 1,2

1 Department of Infectious Disease Control, Municipal Health Service Hart voor Brabant, ‘s-Hertogenbosch, The Netherlands
2 Academic Collaborative Centre AMPHI, Department of Primary and Community Care, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
3 Department Tranzo, Tilburg University, Tilburg, The Netherlands
4 Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
5 Laboratory of Medical Microbiology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands

Abstract

Background:
In The Netherlands, 1168 Q-fever patients were notified in 2007 and 2008.

Patients and general practitioners (GPs) regularly reported persisting symptoms after acute Q-fever, especially fatigue and long periods of sick leave, to the public health authorities.

International studies on smaller Q-fever outbreaks demonstrate that symptoms may persist years after acute illness. Data for the Dutch outbreaks were unavailable.

The aim of this study is to quantify sick leave after acute Q-fever and long-term symptoms.

Methods:
Our study targeted 898 acute Q-fever patients, notified in 2007 and 2008 residing in the Province Noord-Brabant.

Patients from the 2008 cohort were mailed a questionnaire at 12 months and those of the 2007 cohort at 12–26 months after onset of illness.

Patients reported underlying illness, Q-fever-related symptoms and sick leave.

Results:
The response rate was 64%.

Forty percent of the working patients reported long-term (>1 month) sick leave.

Pre-existent heart disease odds ratio (OR) 4.50; confidence interval (CI) 1.27–16.09), hospitalization in the acute phase (OR 3.99; 95% CI 2.15–7.43) and smoking (OR 1.69; 95% CI 1.01–2.84) were significant predictors for long-term absence.

Of the patients who resumed work, 9% were—at the time of completing the questionnaire—still unable to function at pre-infection levels due to fatigue or concentration problems.

Of the respondents, 40% reported persisting physical symptoms at the time of follow-up.

Fatigue (20%) was most frequently reported. Daily activities were affected in 30% of cases.

Conclusions:
Q-fever poses a serious persisting long-term burden on patients and society.

In 2007, the Netherlands began a large, drawn-out outbreak of Q fever, which resulted in thousands being infected and a dozen or so fatalities.

In a study just released in the European Journal of Public Health, Dutch researchers show that many of those infected with Coxiella burnetti previously, now face chronic fatigue syndrome and other physical symptoms.

1,168 Q-fever patients were notified in 2007 and 2008 in the Netherlands. The study targeted 898 acute Q-fever patients, notified in 2007 and 2008 residing in the Province Noord-Brabant. Patients from the 2008 cohort were mailed a questionnaire at 12 months and those of the 2007 cohort at 12-26 months after onset of illness. In the questionnaire, patients reported underlying illness, Q-fever-related symptoms and sick leave.

Some of the key results found in the study include:

• Forty percent of the working patients reported long-term (greater than 1 month) sick leave.
• Daily activities were affected in 30% of cases.
• 20% of respondents reported issues with fatigue.
• 9% of those who did return to work reported they were (up to 2 years post-Q fever infection) still unable to function at pre-infection levels due to fatigue or concentration problems.

Based on the results of the study, the authors conclude that Q-fever poses a serious persisting long-term burden on patients and society.

Q fever is caused by the obligate intracellular pathogen, Coxiella burnetii. The disease is usually transmitted to people through either infected milk or through aerosols.

This disease is found on most continents with the reported incidence probably much lower than the actual because so many cases are so mild.

Animal reservoirs of C. burnetii include sheep, cattle, goats, dogs and cats. In areas where these animals are present, Q fever affects veterinarians, meatpacking workers, and farmers.
…

The mortality rate for acute Q fever is low (1–2%), and the majority of persons with mild illness recover spontaneously within a few weeks although antibiotic treatment will shorten the duration of illness and lessen the risk of complications.

John Chia 1999 about Chronic Chlamydia Pneumoniae:

Chronic Chlamydia pneumoniae infection: a treatable cause of chronic fatigue syndrome.

John K. S. Chia and Laura Y. Chia

Torrance Memorial Medical Center, Torrance, California

…
Over the past 3 years, we encountered 10 of 171 patients with symptoms of chronic fatigue who had elevated titers of antibody to C. pneumoniae long after initial respiratory infection. Most pa- tients had favorable clinical and serological responses to a 1- to 2-months course of azithromycin therapy, although relapse was common. The clinical symptoms of and titers of antibody to C. pneumoniae for our 10 patients over the course of treatment are summarized in table 1.
…

The spontaneous rise of titers for several patients correlated with an increased severity of fatigue and a concomitant increase in respiratory symptoms. This observation suggests that relapses of symptoms could be due to persistent infection with periodic reac- tivation rather than reinfection. All of the patients with relapses responded to additional azithromycin treatment.
…

Collectively, these results suggest that C. pneumoniae is an uncommon yet treatable cause of chronic fatigue. The sensitivity, specificity, and interlaboratory variability of the DNA test will need to be better defined.…

And John Chia 2003 again, this time with his son, about many different pathogens, but obviously implicating Enteroviruses:

Diverse Etiologies for Chronic Fatigue Syndrome

John K. S. Chia and Andrew Chia

I D Med, Torrance, California

Clinical Infectious Diseases 2003;36:671–2
…

Probable cause	Criteria for inclusion	No. of patients (n = 200)
Chlamydia pneumoniae infection	High antibody titer compared with control subjects from the community; response to macrolide therapy	18
Epstein-Barr virus infection	Whole blood (at 1:1000 dilution) or urine sample positive for EBV DNA; response to Val or iv Cid therapya	6
Cytomegalovirus infection	Surveillance of acute infection for a period 16 months; positive culture results; response to iv Cid or IVIG therapy	3
Recurrent VZV infection	Recurrent lesions; response to antiviral drugs	6
Recurrent HHV6-like disease	Recurrent roseola-like illness for a period of 3 years; response to iv Cid therapy	1
Parvovirus B19 infection	Test results positive for IgM or viral DNA	3
Hepatitis C	Resolution of symptoms after interferon/ribavirin therapy	3
Neurocardiogenic hypotension	Initial flulike illness; tilt test positive for NMS; response to midodrine therapy	2
Toxic mold exposure	Documented cultures of environmental samples positive for toxic mold; 11 household member was affected; symptoms improved after leaving the house	2
Postvaccination	Received pneumovax, MMR, or influenza vaccine	3
Enterovirus infection	Persistent, significantly elevated levels of neutralizing antibody for coxsackievirus B or high echovirus titer compared with controls from the community; PBMC sample positive for enteroviral RNAb	109
Unknown	—	44

Chia's study is surely not made to gold standards and any numbers should be taken not to be poured in concrete. Chia claims here to have found enteroviral RNAb in PBMCs, while later he opted to search for enteroviral protein VP1 in gut biopsies - something that seems to me to be unnecessarily complicated. If there is actual enteroviral RNAb in PBMCs in the majority of CFS patients, then Ian Lipkin will find it.

Taken together, it looks like there is a clear indication that different pathogens are likely invovled in different CF(S) subgroups and that there is not one single cause involved in all nor even most CF(S) cases – and though the group of likely pathogens is small, it is not exhaustive. While I am hopeful that it is possible to establish the etiology for a considerable portion of CF(S) cases within the next years, I am pessimistic and think that in the foreseeable future a substantial part of CF(S) patients will remain without a established etiology.

"Infectious mononucleosis-like syndrome probably attributable to Coxsackie A virus infection"

Infectious mononucleosis-like syndrome probably attributable to Coxsackie A virus infection

Burke A. Cunha, Nardeen Mickail, Andrew P. Petelin,

Infectious mononucleosis (IM) is a clinical syndrome most often attributable to Epstein-Barr virus (EBV).

Characteristic clinical features of EBV IM include bilateral upper lid edema, exudative or nonexudative pharyngitis, bilateral posterior cervical adenopathy, and splenomegaly ± maculopapular rash.

Laboratory features of EBV IM include atypical lymphocytes and elevated levels of serum transaminases. Leukopenia and thrombocytopenia are not uncommon.

The syndrome of IM may also be attributable to other infectious diseases, eg, cytomegalovirus (CMV), human herpes virus-6 (HHV-6), or Toxoplasma gondii.

Less commonly, viral hepatitis, leptospirosis, brucellosis, or parvovirus B19 may present as an IM-like infection. To the best of our knowledge, only 2 cases of IM-like infections attributable to Coxsackie B viruses (B3 and B4) have been reported.

We present the first reported case of an IM-like syndrome with sore throat, fatigue, atypical lymphocytes, and elevated levels of serum transaminases likely due to Coxsackie A in an immunocompetent adult.

Hat tip to Tom Kindlon / CO-CURE

(But one person? So they showed in one person that Coxsackie A can do this?)

Vincent Racaniello on poliovirus vaccine litigation

Vincent Racaniello on poliovirus vaccine litigation – a must read in its entirety:

…
Second, a single monkey with a 3-3 neurovirulence score appears to have played an important role in this case, but that ignores the fact that there are almost always wide variations that result in “outliers” whenever biological assays are involved.  We have studied poliovirus infection of mice in my laboratory, for example, and outliers are common – the one mouse in twenty that becomes ill or dies, while the others remain well. Other investigators have shown that poliovirus recovered from the spinal cord of an outlier monkey – one with a 3-3 neurovirulence score – does not produce these results when re-injected in a different group of monkeys. The monkey with a 3-3 score observed in the government’s test of one monopool of type 3 poliovirus vaccine is clearly an outlier. The other 14 monkeys in the intraspinal test had very low scores, and Lederle’s neurovirulence test did not produce a monkey with a 3-3 score. I conclude that the neurovirulence test on this type 3 monopool clearly did not exceed that of the reference virus – there is no scientifically valid justification for arguing otherwise.

If you don’t believe in outliers, there is another way to look at this issue: does a monkey with a 3-3 score in the neurovirulence test mean that the lot of vaccine is more likely to cause paralysis in humans? We cannot carry out such an experiment prospectively, but we can do the next best thing – compare the results of the monkey neurovirulence test with the rate of vaccine-associated poliomyelitis. In the entire history of the monkey neurovirulence test – from 1962-1999 – some monopools of vaccine periodically had one or two monkeys with a 3-3 neurovirulence score, and others did not. Nevertheless, the rate of vaccine-associated paralytic disease remained remarkably constant over this time: 5-10 cases per year. There were no spikes in the years when the “3-3″ vaccines were in distribution. The conclusion is clear: no lot of vaccine is associated with an increase in the number of paralytic cases in any year.

Why do the Sabin vaccine strains cause paralytic disease in some recipients and contacts? Albert Sabin derived these vaccine strains by serially passing neurovirulent isolates in different cell types, empirically identifying viral mutants with a reduced capacity to cause disease. There are few mutations responsible for the reduced neurovirulence of the Sabin strains – 5 for type 1, and 2 each for the type 1 and type 2 strains. These mutations rapidly revert during multiplication of the vaccine viruses in the human gut, and that occurs in every recipient of the vaccine. Within several days, the recipient sheds viruses that no longer bear the mutations that Sabin so painstakingly selected. These excreted revertants, when tested in monkeys, are more neurovirulent than the vaccine that was fed to the recipient.
…

Oral polio vaccine has an inherent risk that public health authorities deemed to be acceptable, given the extraordinary benefits of the vaccine. However, in a sense, the ~400 individuals who contracted vaccine-associated polio from 1962-1999 paid a price for the greater good of the population. For this reason alone they deserved compensation, which is what they now receive under the National Childhood Vaccine Injury Act. Compensation for these individuals is given without the need to castigate life-saving vaccines likes OPV.

Enterovirus related metabolic myopathy in chronic fatigue syndrome (CFS)

Enterovirus related metabolic myopathy: a postviral fatigue syndrome.
(Full text available for free as PDF)
J Neurol Neurosurg Psychiatry. 2003 Oct

OBJECTIVE:
To detect and characterise enterovirus RNA in skeletal muscle from patients with chronic fatigue syndrome (CFS) and to compare efficiency of muscle energy metabolism in enterovirus positive and negative CFS patients.

METHODS:
Quadriceps muscle biopsy samples from 48 patients with CFS were processed to detect enterovirus RNA by two stage, reverse transcription, nested polymerase chain reaction (RT-NPCR), using enterovirus group specific primer sets. Direct nucleotide sequencing of PCR products was used to characterise the enterovirus. Controls were 29 subjects with normal muscles. On the day of biopsy, each CFS patient undertook a subanaerobic threshold exercise test (SATET). Venous plasma lactate was measured immediately before and after exercise, and 30 minutes after testing. An abnormal lactate response to exercise (SATET+) was defined as an exercise test in which plasma lactate exceeded the upper 99% confidence limits for normal sedentary controls at two or more time points.

RESULTS:
Muscle biopsy samples from 20.8% of the CFS patients were positive for enterovirus sequences by RT-NPCR, while all the 29 control samples were negative; 58.3% of the CFS patients had a SATET+ response. Nine of the 10 enterovirus positive cases were among the 28 SATET+ patients (32.1%), compared with only one (5%) of the 20 SATET- patients. PCR products were most closely related to coxsackie B virus.

CONCLUSIONS:
There is an association between abnormal lactate response to exercise, reflecting impaired muscle energy metabolism, and the presence of enterovirus sequences in muscle in a proportion of CFS patients.

(via)

Loren Cordain on Autoimmunity and Nightshades

… experiments in animals confirm that organ specific autoimmune diseases can be caused by injecting a self-antigen with a powerful adjuvant such as Freund’s [33, 34]. Neither the adjuvant alone nor the self-antigen typically results in autoimmunity in animals [33-35].
…

33. Fairweather D, Kaya Z, Shellam GR, Lawson CM, Rose NR. From infection to autoimmunity. J Autoimmun. 2001 May;16(3):175-86.

34. Fairweather D, Frisancho-Kiss S, Rose NR. Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus-induced myocarditis. Rev Med Virol. 2005 Jan-Feb;15(1):17-27.

35. Fairweather D, Rose NR. Women and autoimmune disease. Emerg Infect Dis 2004;10:2005-2011.

A wild guess

So, if we assume that an Enterovirus causes ME/CFS (and Gulf War Illness) and I had to take a wild guess which one, I would pick Echovirus 30 and Echovirus 11.

Data from: Enterovirus Surveillance --- United States, 1970--2005 (cdc.gov)

You can see one wave/peak in the early 1980ties ("Osler's Web"), and one more after 1990 (Gulf War). Two different viruses could explain two different illness presentations (e.g. with/without POTS).

But this is just a wild guess...

Translation and protein processing by picornavirus

Translation and protein processing by picornavirus

The picornavirus RNA binds to ribosomes and makes a single polypeptide, therefore the virus has just one gene. This polyprotein has regions that have proteolytic activity (they are cysteine proteases) that cleave the polyprotein to three precursor proteins (P1, P2, P3). P1 is cleaved to a VP0, VP1 and Vp3 plus a leader peptide of unknown function. VP0 gives rise to VP2 and VP4. P2 and P3 do not give rise to viral structural proteins. One of the proteins that comes from P3 is the VPG that is found at the 5' end of the viral RNA while other proteins from this precursor are the viral replicase and enzymes that modify the behavior of the host cell. P2 is also cleaved to give other cell-modifying proteins. Details of some of the cleavages are still vague.

Once the various viral proteins have been made in the infected cell, the replicase (also call a transcriptase or protein 3Dpol) copies the viral plus sense RNA to negative sense RNA. Other viral proteins are also involved in this process. As new positive strand RNAs are made, they can also be translated into more viral protein. There may be as many as half a million copies of viral RNA per cell. Some of the proteolytic events outlined above take place as the nucleocapsid is assembled. This is especially the case with the VP0 cleavage to VP2 and VP4. P1 protein is the precursor that gives rise to the four structural proteins of the nucleocapsid. Five copies of P1 first associate. Endoproteolysis then occurs to form VP0, VP1 and VP3. Twelve of these pentamers than associate to form an empty capsid (procapsid). The viral RNA now associates with the capsid and at the same time, VP0 is cleaved. Release is by lysis of the host cell.

At the same time as viral protein synthesis is occurring, host cell protein synthesis is shut off. The host cell mRNAs however remain fully functional when assayed in an experimental system, so selective degradation of cell mRNAs is not the reason for protein synthesis inhibition. One way host cell protein synthesis occurs is via the cleavage of initiation factor eIF-4, one of the cap binding proteins of the host cell's ribosomes so that cellular mRNAs cannot bind to the ribosomes. Association with cap-binding proteins is a prerequisite for the translation of most cellular RNAs. Thus, only uncapped messages such as that of the picornavirus are translated. Note that most viruses express capped RNAs similar to normal mRNA and so this mechanism of shutting down host protein synthesis is not available to them. The viral proteins also change the permeability of the host cell, altering the ionic composition of the cell and inhibiting cell mRNA association with ribosomes. Moreover, the large number of copies of viral RNA simply out-compete the cell's mRNAs.

Picornavirus causes MS in mouse model

Multiple sclerosis is an autoimmune disease; the body produces antibodies that attack and eventually destroy parts of the myelin sheath covering our nerves. The cause of MS, like HUS 40 years ago, is unknown, though it's thought to be a combination of genetics and environmental influences. Going through the literature, it seems like almost everything has been implicated as playing a causal role at one point or another: pesticides, environmental mercury, hormones, various other "toxins," and a whole host of microbes, including Chlamydia pneumoniae, measles, mumps, Epstein-Barr virus, varicella zoster (chickenpox), herpes simplex viruses, other herpes families viruses (HHV-6 and HHV-8), even canine distemper virus. They've done this looking at both microbe culture (from blood, brain tissue, CNS, etc.) as well as using serology and DNA/RNA amplification in various body sites. None have shown any strong, repeatable links to the development of MS--much like the spurious associations that were seen with adenovirus and HUS.

Although no microbial agent has been convincingly implicated to date, there are tantalizing hints that MS is caused by an infectious agent. There have been "outbreaks" of MS; the most famous occurred in the Faroe Islands in the 1940s. Studies of migrants show that the risks of developing MS seem to be tied to exposures in childhood, suggesting a possible exposure to an infectious agent as a kid. And one of the most common mouse models used to study MS has the disease induced by infection with a virus called Theiler's murine encephalitis virus (TMEV). If it can happen in mice, why not humans?

What I find interesting is that TMEV is from the picornavirus family, the same family to which enteroviruses belong. So if an picornavirus can cause MS (albeit in a mouse model of the disease), I think it is possible that enteroviruses could cause ME/CFS. After all, ME/CFS has been called at times "atypical MS" and some suspected outbreaks of MS (like Punta Gorda in Florida) might have been ME/CFS outbreaks.

Relation: Infection with Polio to Post-Polio Syndrome

Outcomes of poliovirus infection

Outcome	Proportion of cases
Asymptomatic	90–95%
Minor illness	4–8%
Non-paralytic aseptic meningitis	1–2%
Paralytic poliomyelitis	0.1–0.5%
— Spinal polio	79% of paralytic cases
— Bulbospinal polio	19% of paralytic cases
— Bulbar polio	2% of paralytic cases

.

Progress to post-polio syndrome

Initial polio symptoms	Progress to post-polio later in life
Asymptomatic	?
Minor illness	?
Non-paralytic aseptic meningitis	14% to 42%
Paralytic poliomyelitis	25% to 50%

12 year polio incubation in immune-compromised patient

Analysis of poliovirus recovered from the stool of a patient with fatal poliomyelitis revealed that she had been infected with the virus 12 years earlier, probably when one of her children received the oral poliovirus vaccine. This case has the longest known incubation period for vaccine-derived poliomyelitis, and highlights our still rudimentary understanding of how poliovirus causes disease.
…
This case emphasizes the need to continue research on poliovirus. Our knowledge of how the virus causes disease is still rudimentary – as is evident by our failure to understand the 12 year incubation period of the case described here. Although the polio eradication campaign has had excellent results, it can be compromised by vaccine-associated disease. Individuals with B lymphocyte deficiencies will be a reservoir for the virus and can lead to infections if immunization levels drop. It would be highly beneficial to identify all individuals with chronic poliovirus infections, and treat them with antivirals. Unfortunately, such compounds do not exist – underscoring the need to continue research to identify drugs that can be used to treat poliovirus infection.

Post-Polio Syndrome

Post-polio syndrome (PPS, or post-poliomyelitis syndrome or post-polio sequelae) is a condition that affects approximately 25–50% of people who have previously contracted poliomyelitis—a viral infection of the nervous system—after the initial infection. Typically the symptoms appear 15–30 years after recovery from the original paralytic attack, at an age of 35 to 60. Symptoms include acute or increased muscular weakness, pain in the muscles, and fatigue. The same symptoms may also occur years after a nonparalytic polio (NPP) infection. The precise mechanism that causes PPS is unknown. It shares many features with the post-viral chronic fatigue syndrome, but unlike that disorder it tends to be progressive, and as such can cause a tangible loss of muscle strength. Treatment is primarily limited to adequate rest, conservation of available energy, and supportive measures, such as leg braces and energy-saving devices such as powered wheelchairs, analgesia (pain relief) and sleep aids.

Increased activity during intervening healthy years between the original infection and onset of PPS can amplify the symptoms. Thus, contracting poliomyelitis at a young age can result in particularly disabling PPS symptoms.

Numerous theories have been proposed to explain post-polio syndrome. Despite this, there are currently no absolutely defined causes of PPS.

Diagnosis of post-polio syndrome can be difficult, since the symptoms are hard to separate from complications due to the original poliomyelitis infection, and from the normal infirmities of aging. There is no laboratory test for post-polio syndrome, nor are there any other specific diagnostic criteria. … In general, PPS is a diagnosis of exclusion whereby other possible causes of the symptoms are eliminated.

Sounds like CFS to me! I wonder what happens if you have post-polio and fall into the hands of the psychobabblers: CBT/GET for you! After all, without a definite cause, it must be psychosomatic (sorry for my sarcasm).

But there is some training that should and can be done:

Muscle training at aerobic levels without maximum exercise is useful to maintain muscular function and ameliorate fatigue13 and muscular training in warm water seems to be particularly useful. … Inactivity increases the risk of obesity, diabetes, cardiovascular, and muskuloskeletal problems and so polio patients who take part in physical activity have significantly less symptoms than physically inactive patients. All polio patients with or without post-polio syndrome should therefore be advised to take part in physical activity, but they should not be performing static muscular training at maximum effort (anaerobic level) and they should allow intermittent breaks.

Elisabeth Farbu: Post-Polio Syndrome – Diagnosis and Management

No anaerobic training – same as in ME/CFS.

By the way:

Factors that increase the risk of polio infection or affect the severity of the disease include immune deficiency, malnutrition, tonsillectomy, physical activity immediately following the onset of paralysis, skeletal muscle injury due to injection of vaccines or therapeutic agents, and pregnancy.

And:

The molecular mechanisms by which poliovirus causes paralytic disease are poorly understood. Early symptoms of paralytic polio include high fever, headache, stiffness in the back and neck, asymmetrical weakness of various muscles, sensitivity to touch, difficulty swallowing, muscle pain, loss of superficial and deep reflexes, paresthesia (pins and needles), irritability, constipation, or difficulty urinating.

Enterovirus diagnostic gotchas

In der Serodiagnostik wird der Neutralisationstest (NT) als sensitivste und zugleich spezifischste der konventionellen Methoden für den Ak-Nachweis gegen die verschiedenen Enterovirusgruppen angesehen. Es können die aktuell zirkulierenden Subtypen B3, B4, B5 (selten B1, B2) und Echovirus 30 (selten Echovirus 7, Echovirus 11) untersucht werden
…
Der Enzymimmunoassay (EIA) mit der getrennten Darstellung von IgM und IgG hat sich in der Routinediagnostik [von Enteroviren] aus verschiedenen Gründen nicht durchsetzen können. Als solcher ist insbesondere die hohe Kreuzreaktivität zu nennen. Ein weiteres Problem stellen falsch positive Befunde bei Vorhandensein von heterophilen Antikörpern (z.B. bei EBV, Mykoplasmen) dar.

In English: Enzymimmunoassay (EIA) test for the IgM and IgG enterovirus (coxsackie, echovirus) antibody can lead to false positive results (crossreactivity e.g. with EBV or mycoplasma heterophile antibodies). A more specific test is a neutralizing test.