Swine flu: are we there, yet?

Listening to yesterday's press briefing with WHO's Dr. Keiji Fukuda (audio file here), several things seemed clear to me. The first is that everyone, WHO included, thinks a pandemic is well underway. Second, WHO's efforts to explain why they are not making it "official" by going to phase 6 are becoming increasingly awkward and the explanations manifestly tortured. Essentially what Fukuda said was that WHO was waiting for its member nations to signal they knew it was a pandemic and then WHO would say it was a pandemic. It was reminiscent of the cries of one of the principals of the revolution of 1848 as he chased the mob into Paris's Jardin du Luxembourg: "I'm their leader! I must follow them!" Third, despite Fukuda's calm and measured tone, there was an undercurrent of worry. The severity of the not-yet-called-a-pandemic pandemic is now being termed "moderate" (which seems accurate to me). Fukuda explicitly declined to characterize it as "mild." He also called attention to reports of "disproportionate numbers of serious cases occurring” in Canada's First Nation (indigenous) community. From the Winnipeg Free Press:

There has been a "surge" in the number of people requiring intensive care in Manitoba hospitals with flu-like illnesses, the province said Monday.

As of Sunday night, there were 26 such people in hospital -- more than half of them aboriginal. All were or had been on ventilators due to influenza or of an influenza-like illness. Eight persons with severe cases required hospitalization in the past week alone.
Joel Kettner, chief provincial public health officer, said Monday "most if not all" of the cases are expected to be confirmed as the new H1N1 influenza.

[snip]

Kettner said the 26 people on ventilators in hospital are "very ill."

"Some of them have been on ventilators for several weeks... The pattern has been so far that many of these patients have required several weeks of intensive care before they have recovered."

He said that in the first week of June, the rate at which people became severely ill with what is suspected as H1N1 was far higher than it was in April or May.

More than half of those in intensive care are First Nations people -- status or non-status as well as Inuit.

[snip]

Jan Currie, vice-president of the Winnipeg Regional Health Authority, said there are normally 30 to 35 people on ventilators in Winnipeg hospitals at any one time for a variety of reasons.

The 26 listed by Kettner are in addition to that, she said. The WRHA has acquired 15 extra ventilators and may defer non-urgent procedures that would normally require ICU care. It is also taking steps to provide enough support in intensive-care units and prioritizing patients for personal care home beds.(Larry Kusch, Winnipeg Free Press)

As Fukuda points out, influenza took a heavy toll in isolated and disadvantaged communities in earlier pandemics. This is part of a picture of a well transmitted novel influenza virus, circulating out of season and hitting younger age groups differentially, just what one expects from a pandemic strain based on past experience.

The on-again-now-off-again inclusion of severity as a criterion for a pandemic is currently being spun as a descriptor to give member nation's the best information on the nature of the pandemic they are dealing with. I think that's a sensible attitude, and I don't fault WHO. The politics of any intergovernmental agency, especially in the UN system, produce a difficult and treacherous landscape to negotiate. If you've never seen it close up, it's hard to appreciate the labyrinthine and counter-to-common sense ways of the international community. This is not the UN's fault and certainly not WHO's. It is the system they (and we) are forced to work within, as mandated by the nations of the world. If the space program becomes robust enough, someday you may be able to opt out for another planet. Until then, it's no use complaining.

Meanwhile we now have the long predicted influenza pandemic. It's neither so scary nor so benign that we can afford to either hide under the bed or ignore it. What we must do is roll up our sleeves and manage the consequences.

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While the current WHO Pandemic Alert system is obviously broken, the idea remains a very good one. The reason for its failure was not science although there was some poor science too. The primary problem as pointed out by Revere was the interaction of science and politics.

I don't think anyone who has been even remotely interested in influenza will be taken by surprise when WHO goes to level 6. Partly this is because of the comments made by people like Revere on this and other flublogs and in the MSM that a defacto pandemic has been underway for a while now if not declared by the WHO.

Once this pandemic has passed, there will be time to revisit this issue when tempers have cooled and the political pressures of the moment are long gone. Maybe then the WHO can sit down with the national public health authorities and come up with a new alert phase system. A system that is scientifically rigorous, objective, and one the political leadership agrees not to distort for their own national reasons mid-game.

Grattan Woodson, MD

By The Doctor (not verified) on 10 Jun 2009 #permalink

Interesting that it's hitting hard among First Nations peoples -- many Mexican citizens also have substantial indigenous heritage.

I wonder if there could be a genetic factor of some kind affecting the severity of the illness.

By PennyBright (not verified) on 10 Jun 2009 #permalink

Penny, You would have to compare people who live in crowded and poor conditions versus people who live in uncrowded and good conditions, no matter what race they are. Is this flu focused on the elderly in traditional indigenous populations? No. It's focused on younger persons, just like other in non-indigenous populations. The difference is the conditions in which people are living. Close quarters with all age groups, including children, sharing of towels, cups, utensils, hard to clean surfaces, unemployment stress, diabetes.

An interesting study would be how many children living in a house per each case.

By phytosleuth (not verified) on 10 Jun 2009 #permalink

Penny, Create the conditions conducive to this virus. What health conditions makes it spread more easily? What physical conditions?

Compare people who live in crowded and poor conditions versus people who live in uncrowded and good conditions, no matter what race they are.

The difference in spread and virulence is more likely due to the conditions in which people are living. Close quarters with all age groups, including many children, sharing of towels, cups, utensils, hard to clean surfaces, unemployment stress, diabetes and other health conditions.

An interesting study would be how many children living in a house per each flu case, not what race someone is.

By phytosleuth (not verified) on 10 Jun 2009 #permalink

It appears that CDC is playing down the significance of this outbreak. They started out updating their stats daily and had a separate map for H1N1 cases, then went to 3 times a week updates and combined all flu cases into one map, and now they are down to updating those only once a week. It seems like they think it's all done with.

Dr. Woodson wrote:

âI don't think anyone who has been even remotely interested in influenza will be taken by surprise when WHO goes to level 6.â

Well guess what: We are not the important target audience for the announcement.

There are dozens of countries which are still frantically (and proudly!) trying to catch every incoming person with swine flu. They are quarantining contacts, and sprinkling mini Rapid Response Tamiflu Blankets over everyone nearby. They have not been preparing their populations (see tinyurl.com/kt4lf3 ) for the inevitable failure of containment.

There are scores of countries which do not know that they already have swine flu cases. Most of their people have still never heard of a pandemic, or have only heard of it in the context of the nightmare of âbird fluâ. They are not even familiar with âseasonal fluâ as a concept. When they do hear âpandemic,â it is going to sound unduly scary no matter how WHO communicates.

(Of course, I think the current pandemic is indeed scary â scary at present, but far more scary for what it could become, in various populations and at various times. But at present, it is not a 1918 second wave-like pandemic, and at present it is not the apocalyptic high CFR horror of H5N1.)

These countries â their populations, their politicians, their opposition parties â may demand currently disproportionate responses that will do enormous harm. Even though I think such an âadjustment reactionâ would be brief, it could still be horribly disruptive in these mostly poor countries, and even in better-off countries.

And you donât have to leave the U.S. to find preposterous misleading reporting about Draconian, allegedly ârequiredâ responses to Phase 6. ( tinyurl.com/l7gjy2 , in which officials didnât seem to help the reporter realize that the U.S. is a swine flu pandemic-exporting country, not a pandemic-importing country.)

By acknowledging community spread in Victoria, WHO has acknowledged indirectly, but clearly, that the current situation meets Phase 6 criteria.

I was previously very disappointed ( tinyurl.com/nl4te7 ) that WHO had considered moving the Phase 6 goalposts without acknowledging that the virus had already scored a goal -- sustained community spread in more than one WHO region.

Now WHO states it is not planning to move the goalposts; they just haven't officially announced the new score yet. Their reasons make sense to me as a physician who believes in the Hippocratic Oath, which starts, âFirst, do no harmâ.

WHO's current reason for delaying the announcement, in order to prepare countries to cope with it, is for a reality-based goal: "Do less harm."

One of the most important things WHO should be doing right now, before announcing Phase 6, is to help countries understand and empathize with the likely âadjustment reactionsâ countries will go through ( tinyurl.com/n99vbf ) â early âover-reactionsâ that are usually dissed by leaders and the media as irrational, except when the leaders themselves are over-reacting.

By Jody Lanard (not verified) on 10 Jun 2009 #permalink

I read the WHO press release yesterday and it seemed they are trying to break the news gradually. We are in a phase 6 pandemic. This must be politics and trying to steer between panic and complacity.

The two things that have ominous implications.

1. Spread in the southern hemisphere during their winter. We are there with Australian and Chile. This gives the swine flu something to do during our off season.

2. Spread into the third world, China, India, Africa, Southeast Asia. This is where most of the people live and health infrastructure isn't the best. This hasn't happened yet. Which is somewhat surprising, but it is early in the pandemic.

If both of these occur, the likelihood of a pandemic next year in the northern hemisphere is pretty high IMO. Even if the flu only overwinters down south, it is still high.

About time to start producing a vaccine for the new H1N1.

The commenting feature is having hiccups.

"This gives the swine flu something to do during our off season."

Raven, it's not gone. Check the numbers in all the states. Creeping and jumping in some places. I don't believe that H1N1 hasn't peaked yet in the U.S.

By phytosleuth (not verified) on 10 Jun 2009 #permalink

The (suspected) H1N1 is causing major problems for St Theresa Point with many people having been hospitalized. However, at the community of Cross Lake, which is similar in many respects but with road access, there are many people with flu-like symptoms but they are much less severe. Similarly, in the town of Dauphin (farther south in Manitoba) absenteeism in the schools has been around 30% for the last week or so, with AFAIK no severe cases. I am wondering if there are two variants of the disease present, one producing much more severe symptoms than the other.

St Theresa Point has no road access and is over an hour by air from Winnipeg. An apparently unforeseen complication is that each person hospitalized is accompanied by a family member. These family members are having difficulty in finding hotels willing to accommodate them because of the health risk.

By Richard Simons (not verified) on 10 Jun 2009 #permalink

Phyto,

I agree that genetic background probably doesn't have anything to do with the spread of the disease. What I'm curious about is the severity of the illnesses. I do agree that it would be a tricky thing to study, and possibly a very minor factor. It could be something like higher diabetes rates leading to more people being sick before they get the flu.

Being mestizo, the fact that this disease seems more severe in Mexican and First Nations peoples interests me greatly.

By PennyBright (not verified) on 10 Jun 2009 #permalink

I was previously terrified the rate of virus mutation might be encoded in internal flu genes, and that addressing these potential pandemics will uncork future designer pandemics. But cytokine storm is the byproduct of a virus-produced toxin. This toxin and some resistance from our immune system attacks are much of the internal genes I was worried about.
We have mostly human cell receptors, birds mostly bird, and pigs both. Pigs are not afflicted by cytokine storm. There is no selection pressure for a virus to become especially deadly, and there is selection pressure for a virus to infect more hosts. For this reason H5N1 is deadly and the 50-50 pig cell receptor physiology (1/2 enteric bird cells and 1/2 like human respiratory tract cells) makes piggies the weak link. Between the first and second waves the virus almost certainly mutated either bird to pig friendly or pig to human. If the would've culled there would've been no second wave; all the selection pressure for human pandemic flus is in the 50-50 piggies.

It appears one of the PB1 proteins codes for corrupting the immune system stand-down response in our lungs. The other give Avian Flu some immunity to our immune system's attack. Probably the Hong Kong flu mutated the latter but not the former. Spanish/Avian Flus both. 2009 Swine Flu neither (to date). WHO is right: an Avian Flu pandemic is imminent; will adapt to pigs without showing symptoms (unlike most animals no cytokine storm) and then to us, or less likely right to us. We should be phasing out pig farming where possible and always social distancing pigs from birds.

Hoffman-LaRoche owns the rights to OX40:Ig. A fusion protein that can be delivered by powdered inhalent to force our immune systems to standdown in our lungs while leaving a virus fighting presence. I believe human trails should be fast-tracked and strategic stockpiles immediately be stocked in local clinics; enough to administer to billions of cases. This is a universal lung flu cytokine storm treatment assuming no serious side effect. It will work for all flu varieties including future designer; flus will probably be among the first designer pathogens. Probably it can be administered to other organs overwhelmed too.
To me where this Swine Flu is troubling beyond normal flus is a lack of immunity signals we are ripe. I do believe the unsustained P-2-P H5N1 transmission cases in Asia represent Avian Flu fluking out over halfway to Spanish Flu before mercifully petering out. This heightened rate of natural mutations may be business as usual for the next generation when everyone has a biolab.

By Phillip Huggan (not verified) on 10 Jun 2009 #permalink

Philip: We don't know the mechanism of cytokine storm or even what cytokine storm is in any detail. We've written quite a bit about it here. Go to the sidebar under bird flu biology and you'll find many posts on the subject. Suffice it to say, it is not accurate to say it is the product of a "viral toxin."

Phillip: You misread it. Toxic shock-like syndrome refers to gram negative sepsis, which is very similar to what has been called cytokine storm. Toxic shock is from bacteria. We pretty much know the proteins that the virus makes. No toxins.

Just a thought about immunity and genetics. There can be a connection. This is from Charles Mann's book 1491.

Indigenous biochemistry may also have played a role. The immune system constantly scans the body for molecules that it can recognize as foreign -- molecules belonging to an invading virus, for instance. No one's immune system can identify all foreign presences. Roughly speaking, an individual's set of defensive tools is known as his MHC type. Because many bacteria and viruses mutate easily, they usually attack in the form of several slightly different strains. Pathogens win when MHC types miss some of the strains and the immune system is not stimulated to act. Most human groups contain many MHC types; a strain that slips by one person's defenses will be nailed by the defenses of the next. But, according to Francis L. Black, an epidemiologist at Yale University, Indians are characterized by unusually homogenous MHC types. One out of three South American Indians have similar MHC types; among Africans the corresponding figure is one in 200. The cause is a matter for Darwinian speculation, the effects less so.

"it is not a 1918 second wave-like pandemic, and at present it is not the apocalyptic high CFR horror of H5N1.)"

No Jody, it is pretty much exactly like a 1918 first wave.

We don't know what it will do this fall but the indicators are not good and getting worse.

It now looks like the World Health Organization will be finished at the end of this...

...good riddance!!

I doubt it, Tom, and I hope not.

Revere, I hope your family's coming along all right.

reading: Kindly continue to post. You are interesting.

This is the latest from the WSJ. ''Swine Flu Dont Panic''

Can revere and others please comment on the errors so maybe future media commentators can get it right. !!! Here are a few to start.

''In fact, seasonal flu kills 500,000 people annually world-wide, a staggering death toll that occurs with hardly any of the public losing a moment's sleep over it.''

''U.S. Seasonal influenza kills 35,000 to 50,000 Americans each year''

''Washing your hands is nice, but specialists say that if one of these viruses goes pathogenic, the only thing that will reduce mortality is a good vaccine''

http://online.wsj.com/article/SB124467570858004013.html

Thanks,Dylan. I am usually a total lurker, but I felt it was an important data point that could be of importance.

Revere I maybe suggested too narrow a definition of "toxin", but my link says Avian Flu is like those afflictions (near end of paragraph), not is. What you are describing is an exotoxin. There are other toxins that aren't direct protein products of pathogens.
I've got about 9 windows open now and am fatigued, but if I had to guess, I'd say Spanish Flu has a linear epitope that is very similiar or identical to the amino acid sequence of part our lung tissue or some other post-infection lung surface located substrate. Our immune systems come in and start attacking these virii, and soon begin attacking our own lungs.
Alternatively the virus toxins mimic ligands and/or act as a superagonist to our T-Cells, making them immortal, or perhaps "diverts" the natural shutoff proteins.

I'm not sure if Hoffman-LaRoche owns OX40:Lg either. Some company got taken over by Genentech got taken over by Hoffman, but the wiki also says in 2005 another company bought the small company before Genentech. In any event I don't think this treatment would prototype a drug-resistant flu easily. The drug treats the hypothetical toxin produced by Spanish Flu (and if you are correct it isn't an exotoxin), not the surface structure of the pathogen itself. It need to achieve drug-resistance squared, so to speak.
I'm posting partial analysis because even the science journals are racing at a dead sprint on this one, publishing early and free and stuff; I'm not going to read all this boring stuff only to plaguarize.

By Phillip Huggan (not verified) on 11 Jun 2009 #permalink

Incidentally what put my mind at ease is that RNA flus mutate at full speed by nature. And bird flocks will out output bio-terrorists for at least a decade and a half.

By Phillip Huggan (not verified) on 11 Jun 2009 #permalink

Phillip: Again, I suggest you read some earlier posts here about cytokine storm to get an idea of the the complexity of this dysregulation and the extensive science already done on it. Whatever is happening it is highly unlikely to be explained by a "toxin." Toxic-shock is a syndrome like gram negative sepsis. How these things are or aren't related is still a big puzzle.

There has been some speculation on the role of genetics and nutrition in the severity of the disease. The worst-affected by far community in Manitoba is Oji-Cree and is probably relatively uniform genetically. At least, many are very similar in appearance and there is very little obvious European influence. The community probably has poor nutritional status as, with the exception of some local fish and wild meat, essentially all food is flown in. A 4L (4 quart) container of milk costs about Can$15 with comparable prices for fresh fruit and vegetables. In the past, they grew their own vegetables but this died out about 40 years ago. Diabetes is a major problem.

These factors may well contribute to the severity of the disease, but on the other hand, some other communities are in a similar situation as regards their background, their level of nutrition and the amount of diabetes (this is based on impressions, not hard data) but are, so far, free from severe cases.

By Richard Simons (not verified) on 11 Jun 2009 #permalink

Nobody has mentioned the use of swine as incubaters for the manufacture of parts for human transplants