Swine flu and deaths in healthy adults–cytokine storm?

Over the last 24 hours, I’ve received a few comments and even more emails asking about or discussing the possibility of a “cytokine storm” triggered by the H1N1 swine flu reassortant. Is this what’s happening in the cases from Mexico? Discussion after the jump…

Let me begin with a bit of background on what’s meant by a “cytokine storm.” In response to infection, the body has a number of ways to fight back against the invading microbe. Cytokines are one part of this defense. These are molecules produced by a number of different types of cells in response to infection that act as signals to other cells in the body–telling them to divide, or to produce certain proteins, or to cease their production. They assist, basically, in orchestrating portions of the immune response. A “cytokine storm” occurs when this regulation goes haywire–the very molecules that are supposed to be protecting the body end up causing it harm by responding too strongly to the infection. (Note that this is quite over-simplified; the cytokine response itself is incompletely understood, and other players in addition to cytokines are also involved).

This is where the “young and healthy” issue comes into play. Children have immune responses that are still developing, while the elderly tend to lose some immune function with the aging process. However, the middle age group–roughly age 15 to 50, give or take–tend to have an active, vigorous immune response upon invasion by a pathogen. Most of the time, this keeps us relatively free of disease from microbes, but some organisms tend to trigger this type of hyper-response that actually ends up harming the host–in some cases, fatally. This is what we’ve seen in some cases of H5N1 infection, and what’s been induced in mouse models with the 1918 H1N1 strain.

So, are we seeing this with the reassortant swine H1N1 virus, or should we expect to find that it causes this? Is this why reportedly many of the deaths to date are in the “young and healthy”? Right now, we simply don’t know. As I mentioned yesterday, the data from Mexico (from media reports, at least) are sparse, and only a handful of cases have been confirmed to be caused by the novel swine flu virus. This makes attempts to extrapolate to any larger trends a risky and imprecise endeavor, and the old adage certainly applies: garbage in, garbage out. So right now (again, from media-reported data), we don’t know for sure that there really is a higher number of “young and healthy” dying from this virus than we would expect to see–so whether this trend even exists is a big question mark.

However, even if we do see an excess of deaths in that middle age group, there could be other reasons besides the “cytokine storm.” Perhaps this group has exposures that have made them more likely to contract the virus than other age groups, so the greater number of deaths is simply a result of a greater number of exposed individuals. Perhaps they were less likely to have been vaccinated in recent years, meaning they had no cross-protective immunity. (This also is a big question mark, as we don’t know, even in vaccinated individuals, that any immunity to human H1N1 viruses would confer any protection). Perhaps they’ve simply been more likely to be noticed in this outbreak, and thus their cases have received more attention and were more likely to have been worked up (as far as obtaining a culture, etc.) than those in the typical influenza risk groups. There are just too many unknowns right now to address these questions, but certainly they will be investigated as more surveillance data is collected.

Additionally, other clues may come from additional analyses of the virus itself. In H5N1 and the 1918 H1N1 strains, we know there are certain mutations in both of them that have been associated with increased virulence. When all the genes of the novel swine virus are sequenced, the presence or absence of these mutations can be determined, suggesting it may or may not be likely to induce the type of cytokine response that has been associated with the highly virulent strains. Expect an information overload when researchers have more of a chance to examine the virus itself in greater depth…

[UPDATED: The Washington Post has an article up discussing the infection in young adults in Mexico.]

Comments

#1 mitchell pozner
April 26, 2009

Concerning possibilty. I did order some doses of Tamiflu for the office. Don’t Panic!! Lets talk tomorrw the big question is if the presnt flu vaccine has any cross reactivity can we take those 2000 dioses and use them.
L
#2 bigTom
April 26, 2009

If we do discover that this -or some future epidemic is causing excess deaths via the cytokine storm mechanism, do we have treatments that can mitigate the storm? I.E. do we have some drugs that can temporarily decrease immune system function, and usefully decrease morbidity?
#3 matt
April 26, 2009

Yes, there are drugs that reduce the cytokine storm by reducing the immune response. Less immune response though and the virus replicates out of control and causes disease because of the viremia. Either way you are….
#4 John Evo
April 26, 2009

What is the value of wearing a surgical mask and why not also wear surgical gloves since, presumably, many such viral cases are passed either hand-to-hand or hand touching things like door knobs and rails?
#5 Tara C. Smith
April 26, 2009

John, I have some older posts on masks here and here.
#6 D. C. Sessions
April 26, 2009

why not also wear surgical gloves

You’ve obviously never worn those things for any length of time.

Also, keep in mind that the primary benefit from gloves is in changing them. As in, “put on gloves when approaching the patient, take them off in between patients.”
#7 Jude
April 26, 2009

At my library reference job I handled a frightened customer today who felt the library should start quarantining books received on interlibrary loan from other states until we’re sure that this isn’t an epidemic. They also wanted to know how long the swine flu virus can remain viable on a surface such as a book. I sent them the CDC site, but still–it’s like people are longing to panic.
#8 John Evo
April 26, 2009

Thanks Tara.
#9 John Evo
April 26, 2009

Has anyone seen any demographics for the dead in Mexico? I’m guessing this could be a clue as to how much this could be like 1918.
#10 Paul browne
April 26, 2009

Matt “Yes, there are drugs that reduce the cytokine storm by reducing the immune response. Less immune response though and the virus replicates out of control and causes disease because of the viremia. Either way you are….”

Not necessarily, There was an interesting paper published in PNAS last year where the anti-viral zanamivir was combined with the anti-inflammatory drugs celecoxib and mesalazine 53% of the mice infected with H5N1 survived, compared with 13% in the control group. Importantly the ant-inflammatories didn’t compromise the ability of zanamivir to kill the virus.

Zheng B.-J. et al. “Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus” Proc. Natl. Acad. Sci. USA, Published online on June 3, 2008 DOI:10.1073/pnas.0711942105
#11 tom
April 26, 2009

I realize that the best response to an infection is to get professional treatment. However, for academical purposes, I was also wondering: Is there a way to “self-medicate”? For example, can we slow down or weaken our immune system to avoid the hyper reaction? Eg. by drinking alcohol. Now alcohol is fairly toxic and may make matters worse. But how about Cannabis? I heard it may have cytokine storm inhibiting properties, but could find no substantiated info on that one. And then again smoking can also be dangerous. What’s your opinion?
#12 CK
April 26, 2009

As a history buff, and the infection control nurse for a nursing home chain, I have a slight case of the willies. I spent the afternoon researching and pulling out what we need to do specific to this outbreak. All our plans are in place, now we just reassure the families and play the waiting game. I do appreciate tom’s suggestion about smoking weed to slow the cytokine storm. You may be about to go, but you won’t get a darn!! All the same, I’m researching Paul’s link right now. I love this board.
#13 Zanna
April 26, 2009

Indeed I would be curious about home remedies and over the counter defenses as well. Over 50 million Americans lack access to any sort of professional healthcare, myself included. If I were to fall sick with this I would be on my own. For that matter we have many homeless die of ordinary influenza each winter as it is- there are many for whom there is no comfort in knowing that doctors can save them if only they can afford it.
#14 devildoc
April 26, 2009

Paul brown: “Not necessarily, There was an interesting paper published in PNAS last year where the anti-viral zanamivir was combined with the anti-inflammatory drugs celecoxib and mesalazine 53% of the mice infected with H5N1 survived, compared with 13% in the control group. Importantly the ant-inflammatories didn’t compromise the ability of zanamivir to kill the virus.

Zheng B.-J. et al. “Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus” Proc. Natl. Acad. Sci. USA, Published online on June 3, 2008 DOI:10.1073/pnas.0711942105″

Both those drugs are nonsteroidal, and one is only Cox-2 and the other is supposed to be somehow bowel specific.
It seems either ASA or other NSAIDs would be better.
And there’s always steroids.
Toradol and decadron, maybe?
#15 Patch
April 26, 2009

It’s my understanding, that wearing masks may help people who are already infected, from spreading the virus. In other words, helps to minimize the areosols emitted from sneezing and coughing. So rather than wearing one to protect oneself…you wear them to protect those around you.
#16 Sandie
April 26, 2009

My grandaughter died from A type flu, she was 2 years old. She showed syptoms on the Friday morning (mild flu syptoms and slightly swollen face) she died in the intensive care unit on the Sunday. Doctors could not halt the spread of the cytokine storm once it had started. The coroner recorded a naritive verdict at the inquest saying she was a young healthy girl who died from influenca A that caused a fatal cytokine storm. I just hope that the new flu virus doesn’t cause a pandemic.
#17 Hubbs
April 26, 2009

So just take some prednisone (corticosteroid) to mute the inflammatory response, just like for hives or other allergies.
#18 Snowy Owl
April 26, 2009

Salutations,

Since the diffusion from various medias of the range age of the deaths in Mexico, 25/40, it immediatly evoque 1918 infection reaction. Taking knowledge of the recurrent severe pneumonia in critic patients it evoque cytokines storm.

Simple Vitamin D3 indeed modulate the first immune response thus granthing time for the second more precise immune response once the patient is infected.

Snowy
#19 Tonia Malva
April 26, 2009

Does anyone know how many, if any, people died last year in Mexico from influenza?
#20 Patch
April 26, 2009

Snowy, what about elderberry extract?
#21 Paul Heikkila
April 27, 2009

Might it be that the reason young adults are the principal victims in Mexico is that they are the ones in contact with swine? The observation seems to be anecdotal. Mexican officials didn’t even realize they were looking at swine flu until a week ago, and it has been definitively diagnosed in only a handful of cases. Perhaps the Mexican authorities sent cases involving deaths of young adults to CDC disproportionately because they felt they were anomalous.
#22 MrsJ
April 27, 2009

In regard to self-medicating and damping down a cytokine storm, simple aspirin will do the job, and have the advantage of being antipyretic as well. Keep the patient well-hydrated, and have some expectorants on hand in case the lungs get congested. Be aware that children under 12 cannot take aspirin, and that prolonged use may lead to stomach erosion and bleeding. It will also thin the blood, so it shouldn’t be used in anyone taking warfarin or other blood thinners.

However, if the patient’s temperature rises very high, or they start to lose consciousness, seek professional help immediately.
#23 Cheri
April 27, 2009

Snowy, as Patch is asking, what do you think about using Elderberry Extract (Sambucol/Sambucus)?
#24 J Dillon
April 27, 2009

Responding to mask links above.
Even if the masks make people more conscience of touching their faces I would think that would help. Also from what ive gathered hand sanitizer is better for bacteria, not viruses. Perhaps washing hands in water with some chlorine dioxide would be better?

I believe a full CBRN rated gas mask would be very effective. Filters by Scott, 3m, MSA. P-100 Rated with full nuclear, biological, and chemical.
http://www.aearoweb.com/sites/law/other.aspx Ive used cheap out of date Isreali gas masks on rooms full of chlorine fumes and wasnt very difficult to keep them sealed. Hand over filter opening would tell you quick if you has a leak (you could still breathe).lol

A good ‘home’ air filter that may limit exposure to its immediate surroundings is the IQair models. HyperHEPA® cleanroom-grade high-efficiency particulate arresting filter. Media: wet laid glass
microfiber, mini-pleated with solvent-free separators.

Purpose: control of very fine particles such as
allergens, bacteria and viruses. Surface area: 40 sq. ft.Classification (EN1822): Class H13 at 0-112 cfm,
MPPS efficiency: 99.95% @ 0.22μm; Class H12 at 112–280 cfm, MPPS efficiency: 99.5% @ 0.16μm http://www.iqair.com/residential/roomairpurifiers/healthproplus.php

Ive had this filter for a few years and am very happy with it.

Tara, are all bug docs as pretty as you are? Apologies if out of line. Thanks for the great info.
#25 chuck
April 27, 2009

Would spritzing the mask with bleach help?
#26 Paul Heikkila
April 27, 2009

Has anyone looked into the differences in treatment for flu-like conditions in different countries? Did those who died in Mexico first take home remedies or over the counter products? Were they initially misdiagnosed and perhaps mistreated? Did they take longer to seek treatment than those in other countries?

Were those who died in Mexico actually in good health to begin with or is that just an assumption due to their ages? Were they as healthy as the international travellers who are now being diagnosed with the same condition in the US, New Zealand, and elsewhere?

What other factors might one suggest to account for the absence of the suggested cytokine storm beyond Mexico’s borders?
#27 MarketBlogic
April 27, 2009

Purely from a statistical standpoint, I’m starting to think that this is a ridiculous joke.

According to the most recent CDC data, the U.S., a country of 300+ million people has about 36,000 flu-related deaths per year:

http://www.cdc.gov/od/oc/media/pressrel/r030107.htm

I couldn’t find any data I trusted on annual flu-related deaths in Mexico, but the country has about 107 million people, or about 1/3 the population of the U.S. and on the whole I’d guess their population is slightly more vulnerable to the flu than the U.S., but for these purposes let’s guess that in a typical year Mexico has 1/3 of 36,000 or 12,000 flu fatalities.

According to the Washington Post article, there are 103 official deaths from the flu in Mexico, with all of them being aged 25-50. The article goes on to note that “President Felipe Calderón said Sunday that of the 1,324 patients with flulike symptoms as of Saturday, 929 have been treated and released from the hospital.”

So trying to rough out crude numbers in a badly reported fast moving story, Mexico is officially counting 103 deaths (let’s use a timeframe of a month) with roughly 1,324 patients hospitalized and 929 of those treated and released already.

In a typical month historically, Mexico probably has about 1,000 deaths from the flu and while the majority of those patients are probably outside of the ages of 25-50, not all of them are . . . . . . .

So, I’m starting to have a hard time seeing this flu in its current incarnation (which I think I had and recovered from with no problems, though Relenza gets a little credit after the 2nd day) as anything more than a unique strain of Type A H1N1, suggesting that any prior flu vaccinations and natural exposures provided little or no protection and so this flu kicks like a country mule, as they say back home, but doesn’t do any more lasting damage than THAT.
#28 Snowy Owl
April 27, 2009

Patch and Cheri, Israeli and Oxford proves via Peer review clinical in duly form that eldeberry does indeed slows down the replication of H5N1, in my view and from Elderries (I am Ojibway-Algonquin)it was use for ALL colds.

Definitively a on the counter suggestions.
#29 Joe
April 27, 2009

When all the genes of the novel swine virus are sequenced

Out of curiosity, how long does it normally take to sequence a virus these days?
#30 Charlie Fancutt
April 27, 2009

Tara thanks for providing a such a valuable source of detail and discussion. My question to you or contributors, is could the much maligned (with a perhaps unfair benefit of hindsight) reaction in 1997 of 40 million vaccinations for swine flu, be helping with the mild US reaction?
#31 Charlie Fancutt
April 27, 2009

Is it also possible for a stronger strain to have developed, while the virus was doing its stuff unnoticed in its mild form. However there is then a time lag, where the cases that have traveled and been picked up are the mild strain and the lethal strain hasn’t hit the USA, but will probably soon?
#32 Charlie Fancutt
April 27, 2009

At the risk of overdoing a polite allocation of questions, I have another one. I caught a bad flu flying from Colombia through Miami to Los Angeles last Christmas Eve. What surprises me is not that this happened, but as someone who travels internationally by air heaps (probably 40 flights last year), why aren’t I, in this confined space on the plane or crowded airports and immigration, catching a whole host of things on a much more regular basis? And needing to fly to Venezuela from here in Australia again soon, how risky is this likely to be? I am figuring from this direction and choosing through Santiago, rather than LAX, I should be pretty safe.
#33 Bert Bunting
April 28, 2009

I would be very interested to know if the fatalities in Mexico City were, prior to the disease, a) heavy smokers b) lived in areas of heavy air pollution, thus weakening their lungs.
#34 Charlie Fancutt
April 28, 2009

In seeking an answer to the question I raised earlier I found the information (below). Perhaps a milder version of swine flu is what we are seeing globally, with the delayed lethal “second wave” only in Mexico so far and perhaps how serious it hits people stopping people from traveling with it, unlike a mild version.

http://www.nytimes.com/2009/04/28/opinion/28barry.html?ref=opinion

“What’s important to keep in mind in assessing the threat of the current outbreak is that all four of the well-known pandemics seem to have come in waves. The 1918 virus surfaced by March and set in motion a spring and summer wave that hit some communities and skipped others. This first wave was extremely mild, more so even than ordinary influenza: of the 10,313 sailors in the British Grand Fleet who became ill, for example, only four died. But autumn brought a second, more lethal wave, which was followed by a less severe third wave in early 1919.”

“The first wave in 1918 was relatively mild, many experts speculate, because the virus had not fully adapted to humans. And as it did adapt, it also became more lethal.
In all four instances, the gap between the time the virus was first recognized and a second, more dangerous wave swelled was about six months.”
#35 Charlie ancutt
April 28, 2009

In reply to Bert…

“I would be very interested to know if the fatalities in Mexico City were, prior to the disease, a) heavy smokers b) lived in areas of heavy air pollution, thus weakening their lungs.”

Posted by: Bert Bunting

Hi Bert. The problem I see with this theory is why are the deaths mostly, as reported so far, 25-45 year olds? Surely old people who were long-time smokers, longer time exposed to pollution and have lungs with much poorer heath, would be dying way more.

However if it is the cytokine storm effect causing the demographic, then it might be relevant if the deceased in that demographic are smokers. In the one case study I read about, the young man was talked about by his family (in quite a bit of detail) as very healthy and cycled like 20 km a day, but didn’t mention if he smoked. I am thinking that they probably would have mentioned it, but maybe not.
#36 Jaydon
April 28, 2009

Is the normal flu vaccine able to protect against this swine flu breakout? And the deaths in Mexico, are most of them young adults, or is it following the normal pattern of infecting the elderly and newborn/infants.
#37 Mr X
April 28, 2009

If you really want to prevent this swine flu virus please email us your questions and your email information and we will send you more information on how to prevent this virus email us at swineflucure@gmail.com Thank you.
#38 Charlie Fancutt
April 28, 2009

In seeking an answer to the question I raised earlier I found the information (below). Perhaps a milder version of swine flu is what we are seeing globally, with the delayed lethal “second wave” only in Mexico so far and perhaps how serious it hits people stopping people from traveling with it, unlike a mild version.

http://www.nytimes.com/2009/04/28/opinion/28barry.html?ref=opinion

“What’s important to keep in mind in assessing the threat of the current outbreak is that all four of the well-known pandemics seem to have come in waves. The 1918 virus surfaced by March and set in motion a spring and summer wave that hit some communities and skipped others. This first wave was extremely mild, more so even than ordinary influenza: of the 10,313 sailors in the British Grand Fleet who became ill, for example, only four died. But autumn brought a second, more lethal wave, which was followed by a less severe third wave in early 1919.”

“The first wave in 1918 was relatively mild, many experts speculate, because the virus had not fully adapted to humans. And as it did adapt, it also became more lethal.
In all four instances, the gap between the time the virus was first recognized and a second, more dangerous wave swelled was about six months.”
#39 Jaydon
April 28, 2009

Charlie Fancutt that may be true, but eventually the second wave will come. And if it follows the 1918 epidemic, then a lot more people will die. Yes we do have a greater healthcare system, and greater technology to research the cure, the population has increased to around 8 billion. In the 1918 instance, over half the worlds population were infected, and around half of them died.
#40 Paul Heikkila
April 28, 2009

Charlie ancutt mentions the case of the 20 km per day bicyclist who died. Bicycling may not be the indicator of good health that we might otherwise think when it is done in areas of high air pollution such as Mexico City.
http://www.transalt.org/files/resources/blueprint/chapter18/chapter18b.html
#41 mark
April 28, 2009

There is some natural foods that are useful for cytokine storms here http://www.bird-flu-influenza.com/relenza-tamiflu-alternatives-folk-medicines-antivirals.htm
#42 Michael
April 28, 2009

There is some natural foods that are useful for cytokine storms here http://www.bird-flu-influenza.com/relenza-tamiflu-alternatives-folk-medicines-antivirals.htm

How does this jive with others’ comments that reducing the cytokine storm also reduces your immune response, so you’re screwed either way? What’s the best bet?
#43 George S.
April 28, 2009

>>Charlie Fancutt that may be true, but eventually the second wave will come. And if it follows the 1918 epidemic, then a lot more people will die. Yes we do have a greater healthcare system, and greater technology to research the cure, the population has increased to around 8 billion. In the 1918 instance, over half the worlds population were infected, and around half of them died.>>

This is not true! In the 1918 pandemic, the mortality rate was about 2.5-5% and about 20% of the world population was infected.
#44 Tonia Malva
April 28, 2009

I don’t want to scream ‘conspiracy theory’ but given the statistical info. from marketblogic which referred to the possiblity that mexico has approx. 12,000 flu fatalities per year. Could it be that the various stockpiles of anti virals are coming to the end of there shelf life i.e 3 years from when they were bought in for the expected bird flu pandemic (that didn’t arrive as far as I know). From a pharmaceutical (sales) point of view if the meds aren’t used, the governments may not want to splash out and stock pile again.

Is it me or is the entire world going to go into panic mode every time a virus appears in more than one country. Surely in this day and age of widespread travel that will happen again and again. How lucky for the pharma’s.
#45 Tonia Malva
April 28, 2009

When I looked at this site yesterday I thought I saw some feedback from a doctor or health care professional who was working in Mexico! Did I imagine it or has the entry been removed. Does anyone else remember seeing it. I thought he said that in his opinion anti virals wouldn’t prevent the deaths and made reference to poor sanitation etc.
Anyone see it?
#46 Tim
April 29, 2009

I was impressed by MarketBlogic’s statistical analysis. 100 deaths is not a lot considering that on average, about 1000 are dying a month from normal flu. All the same I’d like to know what to do about a Cytokine Storm (cool, scary name that we’ll be hearing more of). So in sum:

Anti-inflamatories
Asprin (Yeah. I like asprin. But only on a full stomach).
Prednisone/deltasone and other corticosteroids (prescription drugs)
http://en.wikipedia.org/wiki/Corticosteroid
The disasterous Northwick Trial subjects who suffered from a cytokline storm, were treated with corticosteroids.
http://en.wikipedia.org/wiki/TGN1412
Corticosteroids have adverse effects too.

The research recommended by Paul Browne
http://www.pnas.org/content/105/23/8091.abstract
used anti inflamatories, which also have their drawbacks.
Mesalazine
http://en.wikipedia.org/wiki/Mesalazine
Celecoxib
http://en.wikipedia.org/wiki/Celecoxib

Vitamin D3
“Vitamin D3 acts as an immune system modulator, preventing excessive expression of inflammatory cytokines”
http://www.vrp.com/articles.aspx?ProdID=2130

Eldeberry
There is a negative opinion about Eldeberry on the page quoted above with lots of folk remedies.
http://www.bird-flu-influenza.com/relenza-tamiflu-alternatives-folk-medicines-antivirals.htm

Tom’s suggestion of alcohol and Cannabis, is echoed jokingly elsewhere (http://xkcd.com/574/).Sleep deprivation, hard excercise(?), overwork, might also be doable. If you get swine flu, don’t go to bed. Stay home and work all day and night on your autobiography?

These pages tell you what a Cytokine Storm is
http://en.wikipedia.org/wiki/Cytokine_storm
http://www.fluwikie.com/index.php?n=Science.PrimerCytokineStorm
http://en.wikipedia.org/wiki/Cytokine_storm
#47 Tonia Malva
April 29, 2009

Okay found the Doctors comments I was referring to, they were on:
http://news.bbc.co.uk/1/hi/talking_point/8018428.stm
I quote
SATURDAY, 25 APRIL, MEXICO
“I’m a specialist doctor in respiratory diseases and intensive care at the Mexican National Institute of Health. There is a severe emergency over the swine flu here. More and more patients are being admitted to the intensive care unit. Despite the heroic efforts of all staff (doctors, nurses, specialists, etc) patients continue to inevitably die. The truth is that anti-viral treatments and vaccines are not expected to have any effect, even at high doses. It is a great fear among the staff. The infection risk is very high among the doctors and health staff.
There is a sense of chaos in the other hospitals and we do not know what to do. Staff are starting to leave and many are opting to retire or apply for holidays. The truth is that mortality is even higher than what is being reported by the authorities, at least in the hospital where I work it. It is killing three to four patients daily, and it has been going on for more than three weeks. It is a shame and there is great fear here. Increasingly younger patients aged 20 to 30 years are dying before our helpless eyes and there is great sadness among health professionals here.”
Antonio Chavez, Mexico City

Would be interested to hear why he or any one else thinks the anti virals and vaccines won’t have any effect.
#48 Jaydon
April 29, 2009

George S. most of it is true. Fair enough the mortailty rate was what you say it is, but the number of the infected population was 1 billion, half of the world’s population in 1918. The fact is people are dieing from this. It may be because the Mexican healthcare system isn’t as good as that of other countries, and it might be caused by the fact that the pollution is greater in Mexico. But people are still dieing, and one has even been confirmed in the US.
#49 Jack Sareus
April 29, 2009

There are many posts inquiring about treatment for cytokine storm. Recently, a new class of drugs for the treatment of myelofibrosis has emerged known as JAK inhibitors (Janus Activated Kinase Inhibitors). For example, an investigational drug, INCB018424, has demonstrated a significant decrease in cytokine levels in myelofibrosis patients. It is being developed by a company called Incyte Corporation. It is possible that drugs like INCB018424 are useful in the acute phase treatment of cytokine storm (like for a few days) to drastically reduce mortality etc.
#50 Krillin
April 29, 2009

>> There is some natural foods that are useful for cytokine
>> storms here http://www.bird-flu-influenza.com/relenza-
>> tamiflu-alternatives-folk-medicines-antivirals.htm

> How does this jive with others’ comments that reducing the
> cytokine storm also reduces your immune response, so
> you’re screwed either way? What’s the best bet?

Take Tamiflu, anti-viral supplements (listed on that site), and supplements that boost the non-inflammatory part of the immune system, like AHCC. (See http://www.aor.ca/html/readmore/rm100908.php for efficacy vs bird flu.)

AHCC is horribly expensive, so I decided to only start taking it once my pucker factor has been elevated i.e. today. Ordinarily I just take Diamond V XPC, the livestock version of EpiCor. The livestock version is much cheaper and at least as likely to work, since livestock supplements have to have a noticeable effect for customers to buy them, whereas human supplement customers will continue to buy any kind of garbage, even if studies show it to be harmful.

I would also take an ARB (PMID: 11025447) like Indian olmesartan. (Cheaper than a brand name prescription copay!)
#51 dannie
April 30, 2009

how many people died from flu in mexico last year?
#52 George Pacheco
April 30, 2009

My wife and I are traveling to Brazil.
We need to be vaccinated for the Swine Flu or we can’t enter the country.
Wher can i go get vaccinated is it availbale where I live in RI?

I would appreciate someone answer me please.

Thank You
George Pacheco
#53 John Donson
April 30, 2009

Re: BBC “Doctor” Comments
On reading these, I was struck by this comment, which seemed phony to me — what kind of doctor would expect “vaccination” to help with a newly discovered virus, and what doctor would expect a “vaccination” to work immediately? So I must say that I take all of the quotes in the BBC article with a large dose of salt(s)…

http://news.bbc.co.uk/1/hi/talking_point/8018428.stm

Suspect Quote as Follows:

“I work as a resident doctor in one of the biggest hospitals in Mexico City and sadly, the situation is far from “under control”. As a doctor, I realise that the media does not report the truth. Authorities distributed vaccines among all the medical personnel with no results, because two of my partners who worked in this hospital (interns) were killed by this new virus in less than six days even though they were vaccinated as all of us were. The official number of deaths is 20, nevertheless, the true number of victims are more than 200. I understand that we must avoid to panic, but telling the truth it might be better now to prevent and avoid more deaths.
Yeny Gregorio Dávila, Mexico City ”
#54 doci
April 30, 2009

In order to conter the swine flu and the potential of the cytokine storm one must have optimal amounts of vitamin D either from sun or supplementation. The rationale is that optimal D causes the immune system to produce high amounts of antimicrobial peptides which fight the virus by producing pores in the capsid membrane of the virus. Vitamin D also influences the helper-T cells which produce the inflamatory cytokins by limiting their production of the cytokines. Vitamin D also helps regulate better antibody secretion. So go with Vitamin D.
#55 Doci
April 30, 2009

In order to counter the swine flu you must have optimal amounts of vitamin D either from sunlight or supplementation. Optimal D allows one to produce large amounts of antimicrobial peptides which attack the capsid membrane of the virus putting porous holes in it. It is a first line of defense. Vitamin D also affects the helper-T cells which function to produce the inflammatory cytokines. Optimal D modulates these cells so that they do not produce too many of them so no cytokine storm. So go vitamin D!
#56 zemo
May 1, 2009

Yeah, but…Mexicans get ALOT more vitamin D from their
southern location and greater sunlight intensity. Perhaps the Mexicans’ higher vitamin D levels and related immune system composition resulted in their greater susceptibility to the virus and potential cytokine storms. I would guess Vitamin D levels relate somehow to the general susceptibility to ol’ “Captain Tripps.” Vitamin D is probably the grave digger. Vitamin D is the Mexican vulture’s dinner bell. As for Elderberry, I heard that boosts overall cytokine levels by 2 to 6 times normal. Go ahead and fry yourself if you want to. Better fill up the tub with ice and get ready to slide yourself in. Me I’m betting on St John’s wort and zinc. Wish us all rots a ruck.
#57 doci
May 1, 2009

We wish all of you good fortune but most certainly too much vitamin D is not causing one to get the flu. It is actually just the opposite. Of course Mexico gets more sun etc but this does not mean that everyone is out in it for long periods of time making D. Mexicans typically produce more melanin so they actually must stay in the sun for longer periods of time to make the D. Investigations of those encountering serious problems will hopefully show some sort of pattern to the problem. Of course do not go out and scorch yourself to make D. Depending on one’s skin type 15 – 20 minutes is good.
#58 David
May 2, 2009

A report in the London Times today, 2 May that was set out as a Q & A, suggests the cytokine protein is missing from MSFlu.

Any up to date info on this?
#59 Tara C. Smith
May 2, 2009

I’ve not seen anything definitive, but have read several stories that, from the sequence alone, suggest lower virulence than H5N1 or the 1918 strains.
#60 Robert K. Baker
May 3, 2009

Several times it has been asked why, historically, the flu comes in waves, a relatively mild form initially followed several months later by an unusually virulent form. There may be a relatively simple hypothesis that explains much.

Evidence to generate that hypothesis that has been available for at least eight years. No one seems to wants to look at it. I hope some of you will review this material with a fiercedly critical eye. Please don’t be shy.

As far back as 1990 a researcher from the Department of Agriculture and a virologist from Vanderbilt showed that a relatively benign cocksickie virus that infected a selenium deficient patient mutated into something very nearly approximating Keshans. The reason Keshans is so prevalent in certain parts of China is that the soils there are selenium deficient.

There is substantial evidence that relatively mild influenza virus in a selenium deficient host may, but not necessarily will, mutate to a more virulent form. Doses of as little as 200 mcg of selenium a day have a high probability of preventing the wide spread a more deadly mutated virus.

The really scary part for those who are sitting on their hands and ignoring this evidence is that once the virus mutates, if it is passed on to a person who is not selenium deficient, they are as susceptible as those who hosted the mutating virus. No one talks about it. Substantial science has been around for a long time. For example:

“The emergence of new viral diseases or the increase in
infection from known viruses is often attributed to such things
as global warming, destruction of the rain forest, agricultural
practices, etc. However, the influence of host nutrition on the
evolutionary process of RNA viruses is rarely considered. Our
research demonstrates that inoculation of certain strains of
coxsackievirus or influenza virus into Se-deficient mice leads to
the production of more virulent strains of virus.”
J. Nutr. 133: 1463S–1467S, 2003

Google the authors of these studies and the word selenium and you can learn a lot.

More pertinent to the current discussion, a more recent paper that concludes:

“In summary, mice fed a diet deficient in Se develop much more severe lung pathology postinfluenza virus infection than Se-adequate mice. Although the increase in lung pathology was not associated with an increase in viral titer, it was associated with an increase in the mRNA expression of pro-inflammatory cytokines and chemokines and a decrease in the expression of anti-inflammatory cytokines. Furthermore, the immune response in the infected lung tissue was shifted away from a TH1 response and toward a TH2 response in the Se-deficient mice. Our work points to the importance of adequate antioxidant defense mechanisms for protection against viral infection and demonstrates that Se-dependent GSH-Px may play an important role during an influenza-induced inflammatory process.” FASEB Journal express article 10.1096/fj.00-0721fje. Published online April 27, 2001.

This phenomenon would also explain why selenium deficient patients are dying in Mexico. The virus mutates in the selenium deficient host and that host dies. As for the mild effects on Americans, their better nutrition of the American school kids from New York may explain why they have experienced less severe symptoms. It also explains why in 1918 the flu which came in March and April was relatively mild compared to that which returned in September and October and killed more than 500,000.

As is often the case, the answers may not be simple. A later project injecting influenza A/ Bangkok/1/79 in selenium deficient mice. The Se deficient mice developed much more severe lung pathology compared with Se-adequate mice. Immune function was altered in the Se-deficient mice, and the viral genome changed to a more virulent genotype. Next the picture became murkier. As noted before Se adequate mice have little or more protection against the virus mutated in selenium deficient mice.

The next projected indicated that selenium deficient mice infected with a virulent strain, influenza A/Puerto Rico/8/34, fared better than mice that were not selenium deficient. http://www.ncbi.nlm.nih.gov/pubmed/17327475?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed.

, CDC Kesser and the rest of our national health “authorities. They are exclusively focused on the causation paradigm. Prevention is centered on quarantine, if needed with the help of the military, and on “killing the virus”. Another expansion of our federal government.

Why is the government and academia not telling the public there is a good chance this benign virus may emerge in the fall in a much more virulent form.

The various hypoteses arising from this work is worth pursuing. Too many institutions, from WHO to the giant vaccine manufacturers have a vested interest in ignoring relatively inexpensive and effective solutions for containment. Napolitano and Sibelius may be in over their head and the CDC thinking has long been captive of the drug paradigm. The “free market” simply does not even come close to promoting the public good in the area of preventive health. It never has and it never will.

The discussion would not be complete without some discussion of “risk analysis”. Much criticism has been heaped upon the response to the 1976 Fort Dix virus. Referred to often as a “debacle” one person died of the virus, 25 more died from the vaccine and 500 were afflicted with Guillain Barre. This is often cited as a government fiasco, but perhaps only in hind site. No one knows how many people might have died of a mutated virus six months later.

In conventional risk analysis, broadly expressed, if there is a 10 percent chance that an event will occur that will cost $100 million, then it is worth $10 million to prevent it from happening. In real life, neither the numbers nor the outcome is known with certainty, but within broad contours, one can get a feel for it. More important it is a better method of assessing public health responses than simply accepting without thought whatever story will sell newspapers and TV.

If the odds were estinmated at 1 in 20 that the Fort Dix virus would be a repeat of 1918, there would be a reasonable prospect of 12 million dead Americans. If you multiple that number by 1/20th (5 percent) you get 600,000 dead. So, assuming you knew of the vaccine risk, you weigh the risk of 25 deaths and 500 cases of Guillain-Barre against 600,000 dead. The only sensible conclusion is that it was the right decision. Is it unfortunate that 25 died and 500 were debilitated? You bet. But a much greater risk, even at a one in 20 shot, was avoided. If you took that gamble 20 times, you are still talking about only 500 vacine fatalities, unless, of course, the 1918 style debacle came to pass.

Now others can argue that the government did not know what the odds were there would have been a repeat of 1918 what the death rate would have been, or how effective the vaccine would have been in reducing those fatalities. True, but in making public policy decisions, the government has to make its best estimates based on the evidence available and then act.

On the other hand, if the government is going to require individuals to be vaccinated on some theory of serving the “public good” then two things should be considered: (i) if a person chooses not to be vaccinated and the vaccine works, he is the one who suffers and a good reason must be found for not allowing him to choose and (ii) if the government persists in mandatory vaccinations, then the government should compensate the survivors of the deceased and care for the disabled.

So, the picture is not as clear as a superficial analysis might suggest, but the process by which decisions can be intelligently made is relatively straight forward.
#61 Krillin
May 4, 2009

“As little as 200 mcg of selenium”

That’s an overdose for the majority of Americans. The Clark skin cancer study found the lowest cancer rate (not skin, though) in the people who took 200 mcg AND were in the lowest tertile of baseline selenium. And this was in a group selected from low-selenium areas. The average plasma selenium rose to about 180 ng/ml, which is well above the sweet spot of 130-150 ng/ml that epidemiology suggests is optimal for all-cause and cancer mortality. (Pubmed ID: 18299496) The 200 mcg supplement also increased the risk of diabetes for people with higher baseline selenium. For some reason, selenium studies continue to use 200 mcg, resulting in predictably dismal outcomes.

A daily 200 mcg supplement plus an estimated 37 mcg from diet brought me to 150 ng/ml, so I had to cut back. The average American diet provides 106 mcg/day and results in 124 ng/ml, so there’s no way you can justify a blanket recommendation of supplementing 200+ mcg per day.
#62 doci
May 4, 2009

200 mcg of selenium is highly beneficial if taken in the organic form vs the inorganic sodium selenate form which can be toxic. Most supplements come from selenium-enriched yeast and the sodium is mostly in the form of selenomethionine. This is unfortunate since selenomethionine is actually an essential amino acid and so most of it is incorporated into certain body proteins and is unavailable for antioxidant etc activites. However selenium bound yeast do contain other organic selenium compounds useful for the body. Actually the best way to get proper selenium levels is to grow garlic, onions, and crops in the cabbage group in selenium enriched soils. One will them eat foods containing a host of organic selenium compounds which inhibit cancer and may help our immune systems in avoiding the virus. Organic selenium compounds produced include Se-methylcysteine, Se-propylselenocysteine, and the wierd gamma-glutyl-Se-adenosyl-selenohomocysteine. Organic compounds found in the cabbage group also utilize the selenium forming a good assortment of organic selenium compounds. If you garden buy sodium selenate and add it to the soil in the areas where you grow cabbage crops, onions, and garlic. The selenium simply replaces the sulfur normally taken up by these crops. It just might be the real ticket. For further info go to amazon.com and purchase Notes On The Radical View Of Aging.
#63 Krillin
May 4, 2009

“200 mcg of selenium is highly beneficial if taken in the organic form vs the inorganic sodium selenate form which can be toxic.”

The studies finding drawbacks to 200 mcg selenium used selenized yeast. Se-methylcysteine is probably less toxic (it’s what I take), but it is stored as glutathione peroxidase (GPX) just like the other forms, so it’s probably about as bad with respect to diabetes risk. Too much GPX lowers H2O2 too much and screws up insulin sensitivity. Until we get some positive clinical studies on it, I’m not letting my selenium creep above 140 ng/ml.

Selenium supplements and blood tests are so cheap that I don’t see the point of selenium fertilizer.

“Notes On The Radical View Of Aging” looks to me like 1980s-era thinking. Antioxidants may reduce the risk of certain diseases, but they do nothing about aging. Aubrey de Grey’s plan outlined in “Ending Aging” is the only non-delusional way to fight aging, but unfortunately none of the therapies are going to be ready for a very long time.
#64 Paul Heikkila
July 18, 2009

I wonder if one reason the elderly might be less susceptible to this flu is they remember 1918. My parents can still rattle off a list of the kids who were home sick from school and didn’t come back. They’ve heard this flu might be related to the 1918 flu, and they aren’t about to catch it.
In addition, the elderly receive better care than they did in the past. They are aware of hospital-transmitted illnesses such as C.diff., and have learned to take precautions against them. They apply the lessons learned to the flu.
A further point is more and more kids go to summer camp instead of staying with grandma. Lucky grandma.
#65 Paul Heikkila
August 14, 2009

Aren’t we ready to set aside the suggestion that there is a danger of a cytokine storm in the case of H1N1? Tara’s speculations last April were based on limited evidence from a few Mexican cases. Latest indications are that this flu is no more severe than seasonal flu. A healthy immune system ought to be able to handle it and not produce a cytokine response.
#66 Mary Frank
August 16, 2009

Let’s think about this logically, if this were no worse than the regular flu, would we really be at a pandemic level? Stop listening to what you’re being told and start looking at the actions that the government is taking…that should give a good indication as to how serious this situation is/will become. Tara is right on track. If you take the time to research the causes of death for those that have died from h1n1, you’ll notice that a high rate of the “otherwise healthy” people have died with organ failure. With this virus, it’s often the healthy immune systems that are also at risk, as opposed to the usual weakened/elderly/very young. If otherwise healthy young (age 10-50) people are dying from this, how is this like a “normal” flu? What other theories do we have that would even come close to explaining why so many of the healthy are being targeted? And, since this is relatively new, is it really smart to dismiss ANY theories? It’s foolish and arrogant to believe that we know enough about this virus to beat it. We don’t know what this virus is capable of, we don’t have enough answers yet to rule out anything except the fact that this is very much NOT like a seasonal flu.
#67 Paul Heikkila
August 16, 2009

The fact that WHO terms H1N1 a pandemic says nothing of the severity of the illness. It merely indicates how widely it has spread. The suggestion that H1N1 is no more severe than seasonal flu is certainly not mine alone:

http://www.cnn.com/2009/HEALTH/05/04/swine.flu.main/index.html
“”What the epidemiologists are seeing now with this particular strain of U.N. is that the severity of the disease, the severity of the flu — how sick you get — is not stronger than regular seasonal flu,” Homeland Security Secretary Janet Napolitano said Monday …”

The CDC points to one way in which H1N1 is different from seasonal flu. People over 64 are not particularly susceptible to it:

http://www.cdc.gov/H1N1flu/qa.htm
“One thing that appears to be different from seasonal influenza is that adults older than 64 years do not yet appear to be at increased risk of novel H1N1-related complications thus far.”

Tara’s post is dated April 26.
#68 S in PA
September 14, 2009

I don’t know about cytokine storms (sounds scary!) but I came up with a (perhaps wacky) theory last night of why healthy people are dying and it has to do with the theory that H1N1 tries to settle deeper in the lungs than regular flu (which as I understand tends to settle in the upper respiratory tract) and this leads to pneumonia. My theory is that healthy people don’t smoke cigarettes (at least not a lot of them) and therefore don’t suffer from “smoker’s cough”, which could bring up anything trying to settle in. Are there any statistics to show smokers vs. non-smokers who have had H1N1 and how the H1N1 has affected them?
#69 Paul Heikkila
September 15, 2009

S in PA:
There are interesting reports on smokers contracting H1N1 in Hong Kong. Smokers are more apt to develop serious complications than non-smokers, the opposite of your suggestion. The HK data does not indicate that healthy people are the ones who are dying. Those with serious cases of H1N1 predominantly have medical conditions that make them more susceptible. Smoking is one of those conditions.
http://www.bloomberg.com/apps/news?pid=20601202&sid=aSs9.rvfo7g8
#70 Paul Heikkila
October 14, 2009

The NY Times this morning has an interesting article suggesting that overdose of aspirin may have played a role in the high death rate of the 1918 flu.
http://www.nytimes.com/2009/10/13/health/13aspirin.html?ref=science

The surgeon general and the US Navy recommended aspirin as treatment for flu, and JAMA suggested a dosage twice what is considered safe today. This at a time when Bayer had lost the patent on aspirin and competing drug companies waged advertising campaigns for their products.

No data is presented on how many were taking such overdoses or how many deaths might be attributed to them.
#71 jo
October 16, 2009

Green tea polyphenol has potent anti-oxidative activities and anti-inflammatory effects by decreasing cytokine production.
#72 hosting
October 18, 2009

Tara is right on track. If you take the time to research the causes of death for those that have died from h1n1, you’ll notice that a high rate of the “otherwise healthy” people have died with organ failure.
#73 Ray
November 10, 2009

Tara, I found your article helpful in understanding cytokine storm. Are you familiar with any treatments at this time for cytokine storm and are you aware of the research on LEAPS technology to treatment cytokine storm.
#74 Steve
November 11, 2009

I was wondering if by simply keeping your body as alkaline as posible if that would help against a pandemic?
#75 legrand
April 2, 2010

I don’t know about cytokine storms (sounds scary!) but I came up with a (perhaps wacky) theory last night of why healthy people are dying and it has to do with the theory that H1N1 tries to settle deeper in the lungs than regular flu (which as I understand tends to settle in the upper respiratory tract) and this leads to pneumonia. My theory is that healthy people don’t smoke cigarettes (at least not a lot of them) and therefore don’t suffer from “smoker’s cough”, which could bring up anything trying to settle in. Are there any statistics to show smokers vs. non-smokers who have had H1N1 and how the H1N1 has affected them?
#76 hyperhidrosis
February 1, 2011

The worst thing about Swine flu is that transfer out from one people to others.So the good things is that avoid meeting out the people who is infected out by the swine flu or person who got an fever…