TWiV 334 letters

Robin writes (TWiV 332):

Thanks for the wide perspective

The co-option of host machinery to serve essential functions and the concomitant shrinking of genomes can follow two paths thereafter. If the invader earns its keep, it continues as an essential feature for the host, an endosymbiont (or even closer), such as mitochondria (or the retroviral sequences for syncytin protein), both guaranteed transmission as long as there is a host, with the syncytin sequence conserved due to its essential function.

Where the invader confers no benefit on the individual host, it remains in a parasitic relationship. Even if such a virus is incorporated into the germ cell line, there may be no selection pressure to conserve the sequence.

Perhaps all recognisable viral sequences in eukaryotic genomes are either recent or serve important (even if unknown) functions, or both.

On an ecological scale, even parasites serve the wider system, keeping things in balance. The biological imperative of every organism to increase its own biomass is at the root of our motivation to combat infectious disease: it remains to be seen whether Homo callidus can decide when enough is enough with regard to increasing its biomass, and thus earn the title of Homo sapiens.

As was mentioned, the further we stray from the ways of Nature, the further we venture into the realms of the known unknowns, and even more ominously, into the realms of the unknown unknowns, the roosting grounds of Black Swans.

Sunny writes:

Professor Dickson Despommier SHOULD BE REMOVED FROM TWIV!

I am totally joking and actually would like to share my personal opinion about some comments that struck a nerve with me. I mean no disrespect for the CFS community and have no way near the required knowledge to comment on the disease but I was taken aback by the listener letters by Claudia and Mary read on TWiV 331. I don’t think professor Despommier needs me standing up for him but the disrespect shown towards him and other hosts really struck a nerve with me. This show is a public service in many ways and to the best of knowledge none of you are getting paid and you are trying to inform the public to the best of your ability on a broad range of topics. Sure mistakes are made sometimes (“DICKSON!” my best prof Racaniello voice) and most often corrected (DICKSON!), that is how science works after-all. However, calling a emeritus professor of Columbia University uninformed, biased, insulting and dismissive is in fact uninformed, biased, insulting and dismissive in my opinion. Why do we need to personally attack the person rather than having a professional conversation and making sure the correct information is dispersed? As someone who wants to go into the medical field I am aware that in-fact self-diagnosis is something patients do AND IS INDEED A FACTOR IN MEDICINE and is not totally out of the realm of possibility since there is no specific case designation (a billing code is not proof of a definition nor is one IOM report). I think the point that was trying to be made is we just don’t know the exact mechanism or specifics and MORE STUDIES, and MORE MONEY IS NEEDED! But I do agree a clarification was needed and in-fact it was given. It is obvious something is going on we just don’t know what and hopefully with time we can and help all of these people. I think the show has done a fantastic job at trying to inform the public on difficult scientific topics and it is too bad that outside influences are not appreciative of the great effort this endeavor takes and further show disrespect at the hosts because they diverge from one’s personal viewpoint and or agenda. I personally hope more research is done for ME-CFS and a better understanding can be had so people can be helped. Thank you TwiV for all you do, I thought it was important to let you know that the public service this show does is indeed appreciated by this 25 year old male from Seattle who further appreciates science because of this show. Thank You!

Best Regards,

Sunny.U

Robin writes:

MECFS

Maybe multiple different etiologies funneling through a narrow spectrum of symptoms. Something like flaccid paralysis with different viruses, or lumping all cancers together. The unwitting lumping of a heterogenous group of conditions under one label could delay identifying the separate specific conditions.

Maintaining alertness in this regard would be prudent.

Mike writes:

Hello Twivles!

Long time listener, first time caller.  I’m a mathematical epidemiologist at the Institute for Disease Modeling (IDM) in the lovely state of Washington where it is currently overcast and 52° F (11°C).  I’m one of the few people under the age of 50 who is paid to think a lot about polio. A group of us at IDM work with the Global Polio Eradication Initiative (GPEI) to provide analyses to support the polio eradication effort.

On TWiV 331, Rich (?) asked the question: “are there clades of poliovirus and among those clades, can you associate more neurovirulence among one or the others?”

As Vincent suspected, it’s easy and common to look at poliovirus clades (although people tend to say “lineages” or “(genetic) clusters” instead of clades). As part of the global polio surveillance program, every detected polio case gets its virus sequenced by labs within the Global Polio Laboratory Network.  Clusters (clades) are used to keep track of importations, identify polio reservoir populations, and detect vaccine-derived polioviruses since the 1990’s (Kew et al 1995).  Phylogenetic trees and sequences aren’t routinely published, but there is roughly monthly sharing within the GPEI.  A PubMed search for polio molecular epidemiology will get you some published examples.

On to the question.  The short answer is there is no evidence for any differences in neurovirulence among circulating lineages of wild poliovirus within each polio serotype.  From the pre-vaccine era, we know that there are differences in the neurovirulence (paralytic attack rate) across the three polio serotypes (Nathanson and Kew 2010) from roughly 1 in 200 infections are paralytic for wild poliovirus type 1 to 1 in 2000 for type 2. We don’t know why the serotypes have different neurovirulence rates. So, there’s that, but keep in mind that the three polio serotypes are better thought of as three different species rather than as variants within a species. (Vincent, don’t hit me!)

Within serotype, the only known genetic markers of neurovirulence are the attenuating sites in the Sabin vaccine strains, but most of the wild strains (strain=genotype) that have ever been seen have the neurovirulent nucleotides at all the attenuating positions.  The wild strains have lots of changes that are believed to be neutral, but none of those changes are associated with neurovirulence.  By not associated, I mean that there is no epidemiological evidence for differences in neurovirulence within the range of wild genotypes of a single serotype, and the non-attenuating changes that have been tested are neutral (or nearly so) on cell culture and mouse model phenotype assays.

That having been said, there is a nearly complete lack of what epidemiologists call denominator data, and so the epidemiological case for no differences is really weak.  Essentially all the sequences we have come from paralytic cases, and so I don’t see how we could tell whether some strains are producing more cases per infection or not.  A low neurovirulence strain would just be detected at lower rates and we’d never know.  It’s also worth pointing out that the low paralysis to infection rates for polio (let alone EVD68 or whatever is likely less neurovirulent than polio) would make it really hard to detect differences in paralytic phenotype among strains. You’d probably need thousands of infections per strain at least to do the comparison.

There is an interesting published example of polio doing something sneaky that was associated with a change in the phenotype.  Drexler et al (Nature News) showed that an unusual antigenic variant of wild polio type 1 that caused an unusually high case-fatality (paralysis-to-death) rate was better at escaping prior immunity.  I don’t think partial immune escape is really relevant to the original question but it’s interesting.

So that’s a long answer to the question. Are there differences by lineage within the polio serotypes? Maybe, I mean probably yes but not big differences, but I don’t really have the data to know.

Mike

Research Scientist

Institute for Disease Modeling

Wink writes:

 

1. Poliovirus might have evolved to promote hind-limb paralysis because this increases the chance that infectious stool will touch uninfected persons.
2. “Cancer” on PBS was fine, but a bit of Federal propaganda as well. It left the viewer with the impression that ALL was cured due to NCI research, never mentioning the Nobel Prize awarded to Gertrude Elion and George Hitchings.

Wink

Atlanta

Gabe writes:

I’m a long time TWIV, TWIM, TWIP, and Urban Ag listener. I especially enjoy how you insist that all of your guests recount their long, sometimes meandering paths into science.

Anyway, I wanted to correct something you said in your TWiV 331 Passover-edition podcast. You stated that low CSF glucose levels is a sign of viral meningitis, when, in reality low CSF glucose is a sign of bacterial meningitis. My understanding is that the metabolic demand of viruses is not very high, whereas bacteria have more cellular mass to “feed” (due to the order of magnitude size difference) so their metabolic demand is higher. In fact, CSF glucose levels are an important consideration in making a differential diagnosis between bacterial and viral meningitis. Then again, I am a first-year medical student so take what I say with a grain of salt.

Another issue I found with TWiV 331 is that you glossed over the fact that EV-D68 is not found in CSF. I am curious how EV-D68 (or polio for that matter) exerts its neurological effects if it is not found in the CSF? Do virologists understand what is transmitting the pathogenicity of the virus from outside the blood-brain-barrier, to within it?

Finally, in regards to your ME/CFS discussion, I wanted to reassure you that modern medical training puts a lot of emphasis on being compassionate and understanding with our patients.

Love the podcasts, keep em’ coming.

Sincerely,

Gabe

Lance writes:

Dear family TWiVidae,

I am part way through a very interesting TWiV 331. A couple of quick points.

CSF glucose is measured to exclude bacterial infection. If the CSF glucose is more than 40% of the plasma glucose taken at the same time, bacterial infection (i.e. meningitis) is very unlikely, provided the person is not already on antibiotics (or has only recently started). I’m not aware of any infections where CSF glucose goes up (not to say they don’t exist) but the main clinical use is to rule out bacterial infection which is rapidly life threatening and treatable.

Concerning antivirals after the onset of paralysis – I would not necessarily conclude these are of no benefit without any data. There are many examples of treatment with antivirals after the onset of significant neurological signs/symptoms which can still lead to neurological improvement (e.g. acyclovir for HSV encephalitis) and are clearly of benefit. I don’t see why flaccid paralysis should be different, unless the mechanism is immune mediated and not direct viral damage to the anterior horn cell bodies of the spinal cord. There may well not be complete recovery, but given that neurons don’t divide to replace themselves anything you can do to prevent neuronal loss is likely to help. A lesser degree of disability in a ten year old who is going to carry that disability with them for maybe 60 or 70 years is worth giving treatment for. Many neurological infections don’t recover as well as infections in other sites (part of the reason I think they’re so interesting), but they still can be treated with sometimes remarkable recovery. But not always.

Keep ’em coming,

Lance

Dr Lance Turtle

NIHR clinical lecturer in infectious diseases

Institute of Infection and Global Health

University of Liverpool

Emory writes:

Dear TWIV team,

Outside of DC, it is 63 F, Partly cloudy and ridiculously full of tourists looking at Cherry Blossoms.

In episode 331, there was a question posed about what kind of isolation precautions a child that presented in the emergency room would receive. Being a Pediatric Emergency Room Nurse at a level 1 Trauma center, I thought I could share some insight (which is exciting for me as my area of expertise is not generally helpful in the TWIV environment).

The answer is a wonderfully non-specific it depends. Masks are available at the front door for those who wish to wear one or are encouraged by the staff, although compliance is personal and spotty as you can imagine trying to keep a face mask on a 2 year old to be a special sort of challenge. However, the child you are talking about would be in a different category. Children with new onset neuro deficits are not common. This or even moderate respiratory distress would draw the attention of the triage nurse immediately, as both conditions in a child require immediate evaluation. With the child roomed quickly, at the attention of the combined medical staff, he/she would be removed from the general populace but not necessarily isolated. In the ER setting, with a critically ill child the emphasis would be on stabilization and very initial treatment, not achieving a specific diagnosis. With so many other common differential diagnoses (pneumonia, RSV, influenza, asthma) a novel pathogen is fairly low (House not being a great model for medical care). Standard precautions would be used of course, but  An unknown respiratory/neurological illness would generally be on droplet precautions in a PICU/inpatient environment (droplet think flu/rsv but not TB)

Being pediatric emergency medicine specialists, I would say that we do a great job of identifying and isolating patients who present with even diffuse known infectious disease symptoms (Measles, Chicken pox, pertussis), and being so close to the capital we have the luxury of having resources like negative pressure rooms and further training in infection control that a normal community hospital would not. There should certainly be a higher degree of suspicion and one of the greatest deficits in healthcare today is public health surveillance, preparation, and training. That being said, emergency rooms are a dirty environment, especially as we encourage those in need of medical care to just walk through the front door

On the topic of medical research, I think one of the biggest differences is that in other scientific fields saying ‘I don’t know’ is a recognized beginning of inquiry. In medicine, saying, ‘I don’t know’ especially on the level of health care provider to patient is often seen by the patient as a failure or that the MD/NP/Nurse is not trying hard enough (for both parties). Medical/Nursing practice and research is directly personal in a way that other sciences rarely are.

Thanks for doing these papers! There were cases attributed to this outbreak in the area and I enjoyed the teams discussion. Also, please let Dickson off the hook, I think his penance should be considered complete.