The unpredictability of flu and difficulty of making any predictions with confidence is tiring to repeat and tiresome to listen to. Unfortunately that doesn't make it any less true. There are things we know -- because we see them happening -- and things we don't know -- because the information isn't available (like an accurate estimate of CFR or prevalence) or they have yet to happen.
What we know is that we are confronted with a new influenza virus that is spreading with ease outside of its normal season, is infecting an age group that normally doesn't get easily infected (the 5 - 24 year olds), and is causing most of its serious illness and deaths in that same age group. In North America it is now the only significant circulating flu virus, present in all 50 states. WHO's Dr. Keiji Fukuda ((WHO presser .mp3) said yesterday that preliminary data from Chile, in the southern hemisphere, suggests it has similarly displaced the usual seasonal flu strains there. 64 countries have now reported over 17,000 cases and there is no doubt this virus is now a pandemic strain, whatever WHO chooses to call it. So that's what we know, because it is happening and we can see it.
What we don't know is exactly how nasty this virus is or how nasty it might become. The general impression is that clinically it is like many seasonal influenza viruses, producing mild illness in many, a very uncomfortable but self-limited illness in many more, and a serious or fatal illness in some (117 deaths as of Tuesday). However we don't have accurate data from many localities and in others we strongly suspect the reported cases are just the tip of the iceberg. The UK is almost certainly chock full of swine flu cases, although by Monday they had only reported a few hundred. The number is more likely in the thousands. Government officials would rather not know, afraid evidence that sustained transmission was occurring would trigger a declaration of a pandemic, with unknown consequences for international trade and the economy. Said another way, the UK health officials have panicked, along with their counterparts in some other European and Asian countries. Their talk of wanting to prevent hysteria is just a projection of their own mental state. Given the lack of good data, we don't know how bad this virus is with certainty.
But assuming it is as advertised -- a virus that produces a typical flu illness -- we still don't know what it will do from now on. It's the end of the flu season in the north and the beginning of the flu season in the south, but the virus is circulating with alacrity in both hemispheres. On first evidence it is crowding out the previous seasonal flu strains, although this could change overnight. Like all flu viruses, notoriously sloppy reproducers, it will change its genetic characteristics as it circulates in different populations in many different climates and parts of the world. For all we know it will establish itself in other hosts as well. Will it keep going throughout the summer up north? Many experts doubt it, but as of this moment it seems this is a possibility. Flu is notoriously patchy in its distribution, so the variation in prevalence we see in weekly surveillance does not mean it is dying out. But it could mean that. Or not.
Given all the uncertainty, experts are having a hard time arriving at a consistent message. With good reason. They no longer have a firm basis to say anything with confidence. In the UK, noted virologist Dr. John Oxford is quoted as saying there is much more flu than the government is admitting but not to worry: just keep going about your normal activities. Why?
However, he said that people should behave as usual, as far as possible, if a pandemic strikes. "What we don't want is people stopping at home and not going to work, because then you have an economic problem on top of a pandemic," he said. "The best advice is to carry on as normal but to be sensible about it. "This includes a bit of social distancing and shielding people from coughs by coughing into the crux of your arm." (BBC blog)
Being sensible is good advice, but if sensible means "common sense" then we don't need Dr. Oxford (who is not an economist but seems comfortable predicting what will happen to the economy). If sensible means acting according to what science tells us, then we need him although he can't help that much. But most doctors (myself included) don't like to say we don't know or can't help, so we give advice and opinions anyway:
Professor Oxford said that in the next few months, global health officials will be keeping a close eye on what happens to the H1N1 swine flu virus in countries like Australia and South Africa. The southern hemisphere is entering its winter and the peak period for flu. On Friday, the World Health Organization reported that Australia has had 147 confirmed cases; Argentina has had 37; and none so far in South Africa.
What happens in the southern hemisphere in the coming months will be a good indicator of how the virus will behave in Europe and North America later this year. There would be particular concern if H1N1 mutated substantially to become a more virulent illness. Thankfully, there are no signs of that yet.
Makes sense. Except that we can't be sure of any of it and so far nothing this virus has done has been according to expectations. Back to the old adage: hope for the best but prepare for the worst.
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Revere,
What I personnaly heard and reiterated by the Journalist
Who asked the question, in occurence Fergus Walsh.
I asked Dr Fukuda which age groups were most likely to catch the virus and to die from it. "The majority of people who have got infected are under 60 years of age, although some people over 60 have also got infected," he said.
"Those who have got severely ill - with complications such as severe pneumonia and those who have died - have tended to be younger to middle age adults aged 20-40 or so, but not exclusively."
That ties in with the pattern one might expect from a flu pandemic. Normal seasonal flu tends to hit the elderly most severely; in pandemics, it is often young adults who are worst affected.
I clearly hear Dr Fukuda stating that the Furious illness (his quote maybe not yet reported) manifest mostly in the age group 20 to 40 years old, wich is in accordance with past pandemic.
Snowy Owl
According to the local papers, cases have trebled in Scotland over the last week, and one of the cases is looking pretty bad. That's not a good thing, considering it is (at least almost) summer here.
so, outside Mexico we still only have 25 deaths for 13000 cases. Is it reasonable to think that the death count is closer to accurate than the case count. So that's pretty low. We might was well all get infected now and be resistant to it prior to mutation?
As for the pandemic question, WHO clearly needs two words to describe this thing. It's definitely a pandemic with regard to spread, but not anyway serious like the same spread of SARS would've been. As long as the question is only 'pandemic' or not, this is not resolvable. So they need to have one word for spread, and the other word for mortality/morbidity.
This topic of this post relates directly to my comments in the post "Placing a vaccine order with crooks and liars". Readers may like to read my 2 posts there (and Revere's comments), where I attempt to make an intelligent guess at likely case fatality ratios, based on WHO tables of "laboratory confirmed" swine flu cases and deaths by country. To do this I had to correct for the "right censorship" of the deaths. This correction was largely by guesswork since I do not know when the people who died became "laboratory confirmed" cases (perhaps one or two weeks prior to death on average?).
Revere, as a lay person here, I am curious to understand precisely how A (H1N1) and other pandemic viruses manage to displace other influenza viruses that would normally be circulating. Is it that H1N1 is a better infecter/reproducer in its hosts? Doesn't that imply, then, that it regularly co-infects people along with other viruses? And does that then explain some of its propensity to mutate a lot? And, most important perhaps, does it mean that when H1N1 arrives in areas that are H5N1 endemic, it is more likely than not to coinfect people and animals (or at least pigs), so we should be pretty worried about that over time?
Annodeus: You ask a perfectly good question for which I don't have a perfectly good answer. What are some possibilities here?
First, that co-infection, while possible, is less fit for transmission, i.e., if you are co-infected with two, only one is transmitted;
Second, that infection with one virus makes it less likely you will be infected by a second (we know co-infection is possible, because of reassortment, but it might still make a second infection less likely). In that case, the more infectious virus will gain the upper hand;
Third, one virus replicates faster and hence will predominate in a co-infected host (like the first but more specific);
Fourth, that a more rapidly replicating virus is able to overcome host defenses but those defenses are sufficient to knock down a second virus;
Fifth, maybe environmental factors favor one over another and in combination with one of the above mechanisms eliminates one;
Etc. I've probably missed some possibilities. Bottom line: the dynamics are complicated and I don't think we know. After earlier pandemics (up to 1977) we usually had only one seasonal flu A at a time, but as of 1977 we have had H1N1 and H3N2 co-circulating. Some years one would dominate, some years another, but both are present. If novel H1N1 co-circulates with the two existing seasonal flu A's this would be an unprecedented situation, but I don't think anyone is certain it couldn't happen.
Revere-
Over the past several weeks I have, myself, along with so many other readers of Effect Measure, asked you the same questions regarding swine flu over and over again because I think what you are telling us is not what we are expecting to hear--the words, "we don't know." So we keep repackaging our questions because I don' think the "we don't know" part is sinking in!
And I am not making any commentary about the reasons we don't know all we don't know--I am only making the point that I think we are having a hard time processing what you are saying because what you are saying is about 180 degrees from where we expect you to start.
With that in mind, if a major news network were to host a prime time, one hour "expert forum" on issues relating not only to the swine flu, but to pandemic in general, which flu/public health experts do you--you personally--believe would be the best at delivering, articulating and explaining 1)the issues that you are finding we are having the most difficulty in understanding 2)the issues that are most relevant to this swine flu 3)the issues most relevant to pandemic in general 4)the issues that are most relevant to the future of public health as it relates to epidemics (in other words--what can we learn from this--regardless of whether swine flu fizzles out or becomes a monster.)
Let's say it would be a panel of 6--but feel free to give a list of 10 or so for the (hypothetical) news organization to choose from.
I would be interested to hear the opinions from any of you flu scientist/public health professional/journalist/"blogger types"--especially, however, from Revere.
Thanks
melbren: I think my suggestions would meet with some resistance here, but frankly, I think Rich Besser and Anne Schuchat at CDC have done a pretty good job. I also think Keiji Fukuda at WHO has been pretty good at explaining things. That's a pretty "establishment" line-up, but I have to be honest to say I feel they have done it pretty well. Then Jody Lanard or Peter Sandman on risk communication, DemFromCT (aka Greg Dworkin) from the flublogia front would have my vote. When it comes to scientists, there aren't too many I could recommend, I'm afraid. Possibly Lone Simonsen is knowledgeable on past pandemics. I'd have to think about it some more.
Maybe environment (hog farming) or some immune system factor triumphs, but probably the short lifespan and sheer numbers of birds mean they can tolerate lethal flu strains as a species historically. Maybe bird migrations are a factor in flu seasonality.
Present flowchart is: crappy PCR test inconclusive, Level 4 Biolab test reveals novel strain, social distancing and create PCR test and vaccine and heightened surveillence, distribute and monitor better PCR tests, vaccine.
This won't work for 2020-2050(?) designer communicable pathogens. Now there are only maybe half a dozen flu strains circulating every decade. Unlikely for fog-of-war multiple strains originating near simultaneously to corrupt this methodology. I used to think biosensors weren't double-edged fields of knowledge, but on some level they are. Ex) future microfluidics biolab chips that permit sample transport via "digital" droplet volumes may be an at-home platform.
Looking at a graph of the Spanish flu waves, the first wave is too narrow in duration for it to be very communicable. It mutated in between 1st and 2nd waves, either in a human or animal vector, into a more communicable form. The troubling thing to me is the next two waves appear almost identical in shape. This suggests the same style of spread. This suggests no immunity in between first and second waves. I'd a think a 3rd wave that bequeathed some immunity would spread more slowly and be much less lethal.
A hypothesis is there is an inter-species flu ecology that stays at homeostasis for the most part (true in pigs until 1998 and not so much true for people) and then when it is knocked out of whack like pig 1998 triple-reassortment the next months-decade see the odds of future mutations-shifts rise. I used to think future mutations odds were increased after a mutation because whatever reassortment event caused the initial novel strain (say sicks birds have decided to winter in pork sewage lagoon since 2008), was maybe likely in the future. But the inital 1998 triple reassortment triggered 3 more triple-reassortments of novel flu strains in pigs shortly after. Probably a holistic viewpoint is more accurate as it appears the initial shift itself was responsible for three novel strains. New flu strains may trigger a non-linear flu inter-species (or just intra) ecology until things settle down. If so this Swine Flu is troubling, but not so much as I'm guessing the first wave was virulent and not communicable (limited duration) and this Swine Flu appears relatively more communicable and not really virulent (if this Swine Flu had the death toll of first wave I'd expect deaths to smooth over months even with modern air travel). More troubling is the 1998 pig population Swine Flu reassortment event has manifested itself in us 11 years later, after a 1919-1998 stable pig population flu epidemiology. A harbringour for us?
While CDC may be doing a good job on the H1N1 outbreak overall, they and many state and local health departments have not been good on the issue of the protection of healthcare and other workers from exposure to H1N1. The growing body of evidence for airborne transmission is widely dismissed by the infection control community, including the 2007 Institute of Medicine's finding in their report,
Preparing for an Influenza Pandemic: Personal Protective Equipment for Healthcare Workers (http://www.iom.edu/?id=46095):
âWithout knowing the contributions of each of the possible route(s) of transmission, all routes must be considered probable and consequential
â¦â (Institute of Medicine. 2007, p. 53).
The IOM report then further explains:
âCurrent knowledge [of routes of transmission] is fragmentary, and numerous gaps need to be filled in order to make rational and evidence-based recommendations on prevention efforts including PPE design, choice and use.â (Institute of Medicine. 2007, p. 68).
Many state and local health departments have been recommending to hospitals to only provide surgical masks for most healthcare workers for H1N1 protection. Surgical masks do not protect against airborne transmission. The result in great confusion among front line healthcare workers and employers and a missed opportunity to improve the safety culture in healthcare. Healthcare workers have responded in several recent surveys that a sizeable number will not report to work in the event of a pandemic, if they do not feel their employer's health and safety program will not protect them (and their families). Why should not healthcare workers have proper ptrotections?
So does the virus acquire its new skills, e.g. virulence factors, by 1) picking them up from other strains or even bacteria or plasmids? or 2) spontaneous mutations within its own genome, because it doesn't replicate itself very accurately yet reproduces very quickly?
or 3) neither or both of the above?
mdaniel: It is a problem. But without knowing the relative contributions it is hard to give guidance. NIOSH is looking at it (technically they are the group to do it), but CDC is looking at the data on health care workers to see what they can find out epidemiologically. Recommending N95 masks without knowing this has its own problems. They might not protect against airborne spread, either. They need to be fitted, most are meant to be disposable, they are uncomfortable wear and compliance might be an issue. Many people have facial hear which prevents them from working properly. They may be in short supply and they cost more. So if they aren't needed, requiring them or recommending them may do more harm than good. Surgical masks probably provide some protection to others and are a reminder to not touch eyes and nose. But may also not be effective. So what to say is not so obvious, all the need is.
Valerie: There is some controversy about the main drivers of genetic variation. The main view is that it is mistakes in genetic replication that the main driver, with reassortment of large segments also important. The old idea of drift and shift are probably oversimplified, as this swine flu shows. It is technically not shift as it is the same subtype as the seasonal H1N1 but it is sufficiently distant that it is a novel virus. Most of the evidence suggests that flu viruses don't pick up pieces of genetic material from other viruses (only in whole units as in reassortment) but a very small minority claims that homologous recombination is an important driver. I don't want to get into the controversy which sheds more heat than light.
I know next to nothing about flu but here is some wild, ignorant and inevitably simplistic speculation:
Let's break the viral genome into two segments, roughly by the locations of the important functions the genes dictate relative to host cells.
Let's group HA and NA and label them "antigenic" - major functions outside or on the surfaces of host cells - and call the rest of the genes "reproductive" - major functions within host cells.
The seasonal viruses are probably well adapted to human hosts by now - good reproductive genes, limited by the antigenic genes. Novel viruses have good antigenic genes, but their repoductive genes are probably not ideal for replication in human hosts.
I'd guess that the second waves in pandemics are often caused by reassortants containing the antigenic genes of the new strain, and some (most?) of the reproductive genes of a seasonal strain.
So, I think there is a very good chance that infection with the new strain in its present form, or the vaccine currently being developed, will offer protection in a second wave.
If I was in good health and thought my country was low down on the list of vaccine recipients, I'd want to be infected with this virus in its present form.
:)
Joe: this virus has internal genes from swine. You can read something about the genotype here.
Joe: I'm sure the situation is much more complicated than you suggest, but let's continue your model for a bit. Firstly, I take Revere's comment to give support to your picture. However the 'antigenic' (external proteins) genes are also, I believe, largely responsible for the virus's infectivity and transmissability. So the hard part for a new virus is to have 'antigenic/infectivity' genes such that they largely evade the immune system but still result in reasonable infection/transmission rates. Swine flu seems to have found a good mix, while so far bird flu hasn't.
Given that I think (see my previous posts here) that the swine flu CFR looks pretty high (maybe 4-9 times worse than seasonal flu, but this is a very rough estimate) and that its CFR in the age group 5-50 yrs may be relatively much higher still, I think you'd be unwise to not do your best to avoid infection.
Joe, Mathfizz: I'm sorry I wasn't clear. I was not giving support to Joe's comments, which implied that the internal genes of swine flu were like seasonal flu genes. They are in fact swine genes. And the HA and NA also take part in reproduction (getting into and out of the cell, uncoating the virus, etc.). We don't know the main antigens, although HA is certainly one of them. Bottom line: there is no firm basis to predict if we will have a second wave and if we do, what its virulence will be.
"What we know is that we are confronted with a new influenza virus that is spreading with ease outside of its normal season, is infecting an age group that normally doesn't get easily infected (the 5 - 24 year olds)...."
This is quite surprising to me. This age group would seem to be the most easily infected with any influenza.
http://www.shvoong.com/medicine-and-health/1792569-monitoring-impact-in…
Typo in my #9 post. I meant the shape of the 2nd and 3rd wave Spanish Flu death graphs look identical enough to suggest there was no immunity gained from being afflicted with the second wave. Other possibilities though (3rd wave could've been 2nd wave mutated more virulent and communicable).
Regarding future bioterror or even just an influx of novel strains from accidental at home experiments: Right now a swab sample that comes up unknown flu sequence from cheapy tests, goes to a Level 4 Biolab test and gets a thorough sequence after 5-6 days. In the meantime, without an alarming mortality rate it is probably okay to assume the strain is benign; we (apart from prescient Veratect) basically use death tolls over sample surveillence now anyways to identify a pandemic. But in an future era of designer microbes, it may be safest to assume a novel pathogen is deadly in the meantime before Level 4 Biolab sequencing. If Level 4 biolab sequencing doesn't improve yields via robotics or some other future advance, the limited number of Level 4 DNA sequencing will have to be rationed very optimally; a Cambrian Explosion of novel pathogens is likely at some point in the second quarter of this century. It looks like our biosensors will come online in time but our pandemic administrative structures (like ignoring Veratect) are a potential point of failure; may leave us hoping for weak initial designer pandemics and learning on the fly.
Revere: I'd best correct your comment (16) as some readers may be confused. Joe (post 13, para 4, 2nd sentence) says the opposite to what you say in post 16: "which implied the internal genes of swine flu [are] like seasonal flu genes". Joe's point, which he no doubt knew was supported by the fact that the swine flu 'internal/reproductive' genes are from swine viruses, was that perhaps this is typical of novel flu viruses. Joe suggested (para 5) that the next version of swine flu (2010, 2011?) could be expected to have 'internal/reproductive' genes like seasonal flu. But I agree with your last sentence (of post 16), Revere. In fact I read some papers a year or two ago which made it look like high virulence might be more connected with the 'internal/reproductive' genes rather than the 'external/antigenic/infectivity' genes.
mathfizz: I'll accept your correction, although I am one of the readers that is confused. I thought we were saying different things, but it's not a big deal. Regarding the influence of differences in the internal genes for virulence, it is well established that differences in NP, NSq, PB1, etc., are related to virulence. Exactly how and in what combinations we are still puzzling out. We've posted here on it numerous times (try the category, Bird flu/biology for examples).
Thank you Mathfizz and Revere.
I think of this one as a swine virus but I tried to avoid discussing its origin because the genes have all jumped around a bit. The post could have been clearer.
Great comments :)
we should classify the subjects by their amount of
unknownness and publish the list for discussion.
Most papers start with "it is not known"
and end with "more research is needed".
The reveres never get tired to point out what all is not
known about flu. Is the intrinsic unknownness greater
in birdflu than in swineflu ? Greater in colds than
in flu ? Greater in pneumonia than in influenza ?
Seems to me that researchers are competing to claim
for more unknownness in their area.