Reports of a small outbreak of a polio-like disease in California

[Fuschia]

I remember the theory I saw, unfortunately I can't remember who were the authors, but that polio was like a magpie in a garden keeping all the smaller, less aggressive birds (other enteroviruses) at bay. Once polio was eradicated from the intestinal tract the other enteroviruses had a chance to take over. There's 60+ species of enterovirus, which, according to the authors, is more than there was pre-polio because now the others have a chance to flourish...

 

[Forebearance]

Yeah, I remember that theory, too, Fuschia. Although I also can't remember the name of the guy who first proposed it. It still seems possible, given the correlation between the rise of polio vaccine and the rise of ME/CFS.

 

[biophile]

“Thus far, the department has not identified any common causes to suggest that the cases are linked."

"We want to temper the concern because, at the moment, it does not appear to represent a major epidemic."

http://www.nbcnews.com/health/health-news/california-polio-illnesses-not-linked-officials-say-n37851

"The CDC is aware of the small cluster of cases in California but is not actively involved in an investigation, a spokesman told CNN. Waubant and her colleagues don't want to alarm anyone with their case report presentation; they're simply seeking help in finding the cause of these seemingly connected cases."

http://www.cnn.com/2014/02/25/health/california-mystery-disease

Tweets the doctors on smart phones while playing golf, partying like it's 1984?

 

[Hip]

Enterovirus 68 has hit several other parts of the US and Europe over the last five years:

Clusters of Acute Respiratory Illness Associated with Human Enterovirus 68 --- Asia, Europe, and United States, 2008--2010

Enterovirus 68 symptoms include: cough, difficulty breathing, intercostal retractions, wheezing, asthma exacerbation, bronchiolitis (a lower respiratory tract infection) and pneumonia. However, the full spectrum of illness that EV-68 can cause is unknown.

Enteroviruses in general cause symptoms that typically include: mild upper respiratory illness, febrile rash illness, and neurologic illness (such as aseptic meningitis and encephalitis). By contrast, EV-68 has been associated almost exclusively with respiratory disease. Nevertheless, EV-68 has occasionally caused central nervous system infection.

Enterovirus 68 shares biological and molecular properties with both enteroviruses and rhinoviruses. Enteroviruses are normally acid resistant which enables them to replicate in the digestive tract. However EV-68, like rhinoviruses, is acid sensitive, which may explain why EV-68 has only been found in the respiratory tract, and not the digestive tract.

I believe that enterovirus 68 tends to cause acute infections only, and has no connection to ME/CFS. ME/CFS is linked to the enterovirus species coxsackievirus B and echovirus.


Refs:
Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses

Enterovirus 68 among Children with Severe Acute Respiratory Infection, the Philippines - Volume 17, Number 8—August 2011 - Emerging Infectious Disease journal - CDC

 

[Valentijn]

Enterovirus 68 has hit several other parts of the US and Europe over the last five years:

Interesting, looks like it was going around the Netherlands right before my acute ME symptoms started.

 

[Firestormm]

Virology Blog: Polio-like paralysis in California: 27 February 2014 Vincent Racaniello

Recently a number of children in California have developed a poliomyelitis-like paralysis. The cause of this paralysis is not yet known, and information about the outbreak is scarce. Here is what we know so far:

• At least 5, and perhaps as many as 20 children have suffered weakness or paralysis in one or more limbs. The median age of the patients is 12 years and the cases have been reported since 2012.
• One group of 5 patients recently presented at the American Academy of Neurology Annual meeting developed full paralysis within 2 days, and have not recovered limb function in 6 months.
• The cases are all located within a 100-mile radius.
• A mild respiratory illness preceded paralysis in some of the children.
• Enterovirus type 68 has been recovered from the stool of some of the patients.

I do not have any more information on this outbreak other than what I’ve obtained from ProMedMail. I have worked on enteroviruses, including poliovirus, for over 30 years, so I thought I might speculate on what might be transpiring.

Read more...

 

[Bob]

Virology Blog: Polio-like paralysis in California: 27 February 2014 Vincent Racaniello

Rancaniello says entero-viruses often can't be detected in the blood, or the stool, even when causing symptoms.
It reinforces my view that lipkin should have been looking in other tissues.
But didn't lipkin say that he'd expect to find any virus in the blood, if it was present, or something along those lines?

 

[Simon]

Rancaniello says entero-viruses often can't be detected in the blood, or the stool, even when causing symptoms.
It reinforces my view that lipkin should have been looking in other tissues.
But didn't lipkin say that he'd expect to find any virus in the blood, if it was present, or something along those lines?

Do you know why he says they can't be detected? Lipkin is using highthroughput unbiased sequencing so is no restricted to searching for specific enteroviruses as would be this case if screening with a panel. If you can point me to the relevant bit of the podcast I'll take a listen

 

[Firestormm]

It is an article not a podcast Simon.

 

[Bob]

Rancaniello says entero-viruses often can't be detected in the blood, or the stool, even when causing symptoms.
It reinforces my view that lipkin should have been looking in other tissues.
But didn't lipkin say that he'd expect to find any virus in the blood, if it was present, or something along those lines?

Do you know why he says they can't be detected? Lipkin is using highthroughput unbiased sequencing so is no restricted to searching for specific enteroviruses as would be this case if screening with a panel. If you can point me to the relevant bit of the podcast I'll take a listen

Actually, I may have read too much into what he said...

Stool is generally the most sensitive specimen for establishing an enterovirus infection. However, the virus may no longer be present at onset of symptoms.

In one study of non-polio AFP in India, no virus could be isolated in 70% of the cases.

The above quotes are a bit vague, so my interpretation was a bit hasty.
However, judging by these quotes, it does seem as if enteroviruses may be very difficult to detect (in blood or stool), even when symptoms are present.

 

[Bob]

A snippet that is relevant to our discussions:

Vaccine-derived polioviruses can cause paralysis but the US has not used this type of vaccine since 2000.

 

[Simon]

It is an article not a podcast Simon.

So, now I've read it, here are some highlights:

[final pare] The paralysis might not even be caused by an infection. At this point a great deal of basic epidemiology needs to be done to solve the problem – if indeed it can be solved at all. Based on its population, California would be expected to have about 75 cases of acute flaccid paralysis each year of various etiologies, suggesting that the current number of cases is not unusual or unexpected.

So this might me much ado about nothing.

Enterovirus infections of the respiratory and gastrointestinal tracts are very common and often do not result in any signs of disease. Random samplings of healthy individuals frequently demonstrate substantial rates of enterovirus infections.

This is why Lipkin was so keen to have a large sample and geographically matched controls in the pathogen study: lots of viruses often don't cause symptoms, so you need to be sure that at the very least a given virus occurs more often in the patient population than controls: presence of the virus alone tells you very little.

 

[Firestormm]

Much obliged. Thank you Bob and Simon

 

[Hip]

@Simon

If you delve into the enterovirus research of and articles about Dr John Chia, you will get all the technical details of why chronic enterovirus infections are very hard to detect.

Briefly, in chronic enterovirus infections (involving coxsackievirus B or echovirus, the two species of enteroviruses linked to ME/CFS, and to chronic hearts diseases like myocarditis and dilated cardiomyopathy), very few viral particles are to found in the blood. Much of the viral activity occurs purely within human cells (as an intracellular infection), where it cannot be easily detected.

This intracellular enterovirus infection is known as a non-cytopathic enterovirus infection. Dr Chia and others (like researcher Dr Nora Chapman) suggest that these non-cytopathic enterovirus infections within cells may be causing much of the symptoms of ME/CFS. These non-cytopathic enteroviruses are certainly linked to chronic heart infection and heart disease.


Although lots of antibodies are made during the acute phase of an enterovirus infection, Dr Chia found that very few antibodies are made once the enterovirus infection enters its chronic stage. So nearly all antibody blood tests for enterovirus will come back low or negative in enterovirus-associated ME/CFS patients.

However, if you take a sample of stomach tissue from such patients, as Dr Chia did in his published research, then you find that this tissue is loaded with enterovirus VP1 protein (in 82% of ME/CFS patients, compared to 20% of controls). The gut is the major home of enteroviruses in the body, which is why this is a good place to look for them.

Dr Chia found evidence of both non-cytopathic enteroviruses (that live inside cells), and regular enteroviruses (that live in the blood and tissues) in the stomach biopsies he took.

Note that the non-cytopathic enterovirus is also called: the non-cytolytic enterovirus, terminally-deleted enterovirus, and the defective enterovirus. These are all synonyms.


Some references:

Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach
John K S Chia, Andrew Y Chia

The role of enterovirus in chronic fatigue syndrome
Chia JK

Persistent coxsackievirus infection: enterovirus persistence in chronic myocarditis and dilated cardiomyopathy
Chapman NM, Kim KS

 

[alex3619]

Rancaniello says entero-viruses often can't be detected in the blood, or the stool, even when causing symptoms.
It reinforces my view that lipkin should have been looking in other tissues.
But didn't lipkin say that he'd expect to find any virus in the blood, if it was present, or something along those lines?

I think Lipkin intends to look elsewhere. The first release of results was only for serum and spinal fluid. It was only a beginning. The next big one is the gut microbiome for him. I don't think Lipkin intended for non-lytic viruses to be detected in blood, for example. I suspect he might intend to keep looking, funding permitting, until he finds something or everything tests negative.

 

[MeSci]

I haven't read this whole thread yet, and haven't yet searched for other threads on this outbreak, but want to post this update from Physician's First Watch before I absent-mindedly delete or forget it!

Cause of Acute Limb Paralysis in Children Still Unknown
By Cara Adler
Edited by
- Andre Sofair, MD, MPH, and
- William E. Chavey, MD, MS

The CDC's ongoing investigation of recent clusters of acute limb weakness in children has not yet identified a cause, according to an MMWR article.

Over 100 cases have been reported in 34 states. Case criteria include acute onset of focal limb weakness; age 21 years or younger; onset on or after August 1, 2014; and MRI showing spinal cord lesion largely restricted to gray matter.

An investigation of 88 cases reported through mid-November found:

-- Upper respiratory tract samples tested positive for enterovirus-D68 in 20% of 41 patients, and for other enteroviruses or rhinoviruses in 22%.
-- Cerebrospinal fluid testing showed no enteroviruses or other pathogens.
-- 36% of patients had no improvement in clinical status after a median 19 days' follow-up.
-- No deaths have been reported.

Link(s):
MMWR article (Free) http://click.jwatch.org/cts/click?q=227;68121869;nqx7TuL3hi2T8G1lEH0XRGAMkxgI9LdPk/Bz/A7SOEQ=
Background: Physician's First Watch coverage of CDC's search for cause of acute limb paralysis in children (Free) http://click.jwatch.org/cts/click?q=227;68121869;nqx7TuL3hi2T8G1lEH0XRLuJMEZuKjwZk/Bz/A7SOEQ=
CDC website on investigation of flaccid paralysis in children (Free) http://click.jwatch.org/cts/click?q=227;68121869;nqx7TuL3hi2T8G1lEH0XRMzzG6nc0yT8k/Bz/A7SOEQ=
CDC's interim clinical management considerations for acute flaccid paralysis in children (Free PDF) http://click.jwatch.org/cts/click?q=227;68121869;nqx7TuL3hi2T8G1lEH0XRGOnSZi9Lfugk/Bz/A7SOEQ=

I recommend the first link, and the link from that link:

4. CDC. Acute flaccid myelitis: interim considerations for clinical management. Atlanta, GA: US Department of Health and Human Services, CDC; 2014. Available at http://www.cdc.gov/ncird/downloads/acute-flaccid-myelitis.pdf .

 

[MeSci]

Briefly, in chronic enterovirus infections (involving coxsackievirus B or echovirus, the two species of enteroviruses linked to ME/CFS, and to chronic hearts diseases like myocarditis and dilated cardiomyopathy), very few viral particles are to found in the blood. Much of the viral activity occurs purely within human cells (as an intracellular infection), where it cannot be easily detected.

By blood, do you mean plasma/serum? Can viruses be found in blood cells?

 

[Hip]

By blood, do you mean plasma/serum? Can viruses be found in blood cells?

Dr Chia I believe is referring to the whole blood when he says the enterovirus load is very low. To quote Chia:

"We can do a quantitative RT-PCR to look for the gene of the virus in whole blood in a patient with ME/CFS, but this has a very low sensitivity because the viral load is very low".

Source: Invest in ME London 2010 ME/CFS Conference DVD

Nevertheless, enterovirus can be detected in blood cells of ME/CFS patients: see this paper.

 

[Bob]

I haven't read this whole thread yet, and haven't yet searched for other threads on this outbreak, but want to post this update from Physician's First Watch before I absent-mindedly delete or forget it!

Interesting. Thanks for posting, MeSci.

There seem to be some similarities to some of the early outbreaks of ME, but I'm not sure how similar.
And the CDC seem to be taking it quite seriously on this occasion. No mention of hysteria, or anything like that!

If they get to the bottom of this illness, perhaps it might help some ME/CFS patients.


Below, I've extracted some notes from one of the CDC's webpages...
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6353a3.htm?s_cid=mm6353a3_x

Symptoms:
acute limb weakness among children
distinctive abnormalities of the central spinal cord (i.e., gray matter) on magnetic resonance imaging (e.g. a spinal cord lesion largely restricted to gray matter in a patient aged ≤21 years.)
neurologic symptoms
respiratory or febrile illness preceding the onset of neurologic symptoms


"These cases coincided with a national outbreak of severe respiratory disease among children caused by enterovirus D68 (EV-D68) (2)."

"Among 71 patients with cerebrospinal fluid testing performed by their health care providers, state and local public health departments, or CDC, no enteroviruses or other pathogens have been confirmed to date. Among 41 patients whose upper respiratory tract samples were available for enterovirus/rhinovirus testing at CDC, 17 (41%) tested positive: eight (20%) for EV-D68 and nine (22%) for eight other enterovirus/rhinovirus types. Of the 19 patients whose upper respiratory tract samples were obtained <14 days from respiratory illness onset, 10 (53%) were positive: seven (37%) for EV-D68 and three (16%) for rhinoviruses. Laboratory testing for other pathogens is ongoing."

"Limb weakness was asymmetrical in most patients."
"Cranial nerve motor dysfunction was reported in 30 (34%) cases."
"Six (7%) patients had altered mental status."
"Three (3%) had seizures."

"Most patients reported a respiratory illness (81%), a febrile illness (68%), or both, occurring before neurologic symptom onset."

"Among 86 patients for whom past medical history was reported, 65 (76%) were previously healthy, and 21 (24%) had underlying illnesses, most commonly asthma (nine [10%])."

"All but one patient was hospitalized because of neurologic illness, and 17 (19%) required ventilator support."

"Among 80 patients from whom cerebrospinal fluid was obtained, 68 (85%) showed a moderate pleocytosis and normal or mildly elevated protein."

 

[MeSci]

Something that stood out for me was the asymmetry, which I don't think is typical in ME. However, I did suffer a unilateral facial palsy at age 5, soon after a bad case of chickenpox, I think (unfortunately all my childhood medical records have disappeared/been lost, which is enormously frustrating).