Swine flu: afternoon briefing

Last, 3rd edition, lists an entry for "case fatality rate" but none for "case fatality ratio"... the case fatality rate, is, however, a ratio (one thing divided by another), not a rate (number of events [e.g. deaths] divided by exposure [e.g. person-months]).

The "case fatality rate" is a ratio...

I think it's OK to *call* the CFR the case fatality rate, since it's become a kind of "term of art" and even the Dictionary of Epidemiology uses that term [at least in the 3rd ed, which is not the most recent].

But it is indeed useful to remember that the CFR, whatever you call it, is a ratio not a rate.

Not to split hairs while Rome burns but some folks may wonder why it's called a rate...just because it started erroneously and the name stuck, is the answer.

I wasn't on the conf. call, but I got some of the CDC memos. Thanks for this great and concise summary, though.

I'm irked, though, because I'm taking a holiday in Mexico in June.

Do we at least know the median age of fatalities in the Mexican cases ?
Have the sequences of the "Mexican" cases (fatalities in particular)been released and/or compared to "our" cases?

I'll go against the grain and say I wouldn't raise to 4 unless it appears the NY cluster is spreading beyond control or deaths outside Mexico. The Apr/27 news story I read says NYC officials hadn't yet noticed a rise in ER flu admissions. Geez it takes 6 days to sequence NY school suspected illnesses (story today says won't be ready until Sunday)? If there was evidence of a flu bug in NYC, I guess pre-emptively go for it. WHO Stage 4 for is Mexico now, maybe minus deaths, in another region. Stage 5 is in 3 or more regions. If there are 200 students sick with flu in NYC, I guess borderline, but it contradicts the news article I read yesterday. To my knowledge there has not yet been a rise in ER flu admissions in cities with confirmed infected cases, outside Mexico.

The Scotsman (Edinburgh) newspaper report:

http://www.scotsman.com/latestnews/Scottish-holidaymakers-diagnosed-wit…

"In addition, there are currently a further seven people among the 22 who have been in contact with the two infected people, who have now developed mild symptoms and are being appropriately cared for."

Nothing definite there, but interesting.

So what are the key statistics here? Which of these will tell us the most about how the outbreak will proceed? What outcome will worry the CDC/WHO? In other words, what information will prompt a rational person to go buy a N95 mask?

Dizzy; Sorry about the confusion over flu wiki. Yes, very interesting. Tells us something about transmissibility. Depends on details, but sounds pretty transmissible.

So is there any speculation yet on why we're seeing mild symptoms here, but large numbers of fatalities in Mexico?

WHO revises scale for pandemic alerts
27 Apr 2009 19:39:19 GMT
Source: Reuters

GENEVA, April 27 (Reuters) -

The World Health Organisation (WHO) revised on Monday its 6-point scale for pandemic alerts, saying that phase 5 would correspond to a strong signal that a pandemic is "imminent".

The revised scale was published ahead of a decision by an advisory body of experts on whether to raise the alert level from the current level of 3.

In a report posted on its website, the WHO said that under the new criteria:

* Phase 4 is characterised by human-to-human spread of a new virus able to cause community-level outbreaks

* Phase 5 is characterised by human-to-human spread of the virus into at least two countries in one region

* Phase 6 is a global pandemic characterised by widespread outbreaks in more than one region.

"While most countries will not be affected at this stage, the declaration of phase 5 is a strong signal that a pandemic is imminent and that the time to finalise the organisation, communication and implementation of the planned mitigation measures is short," it said.

(For more Reuters stories on swine flu, click on [nFLU]) (For more Reuters swine flu coverage, please click here: http://www.reuters.com/news/globalcoverage/swineflu ) (For WHO information on swine flu, go to: http://www.who.int/csr/disease/swineflu/en/index.html ) (Reporting by Stephanie Nebehay and Jonathan Lynn)

what is with all this research which you were talking about since years, how flu spreads, whether swine,ferrets,mice can get it, can reassort, testing possible resistance mutations, developing new drugs, understanding the immunity,...
This should all be increasingly important and urgent now.
Is it being pushed ?
What about international panflu research coopration ?

Fred McFadden: Besser was careful to avoid speculating, but he did say we should expect the "spectrum" of the disease to change in the US. Perhaps there are comorbidities in the Mexican fatalities? It is very frustrating waiting for information from Mexican authorities. CNN's Dr Gupta is in Mexico City now so hopefully we'll learn something soon.

Woke up this morning (in New Zealand) to hear that three of our suspected swine flu cases, have been confirmed as NOT having swine flue. Some good news.

http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10569031

There is a great story about the spread of the illness and the effects that it is having on consumer confidence and trade. here:http://www.newsy.com/videos/the_world_on_swine_flu_alert/
As health professionals, do you think the flu will become widespread in the U.S.

In this audio (http://video.corriere.it/?vxSiteId=404a0ad6-6216-4e10-abfe-f4f6959487fd… ) Ilaria Capua, who is known in the flu world for her passionate behaviour during the bird flu top period, essentially says that the genetics of this swine flu virus is not similar to the 1918 flu, but it's more similar to the 57/58 and 68/69 ones. She is not worryed about this virus for now.
What do you think?

I really appreciate you posting this. It is quite difficult to follow this thing via the standard news channels, even the decent ones. The news coverage has been insane, absolutely bonkers crazy, and very few knowledgeable reporters are asking the right questions.

For example, just a minute ago, Marc Ambinder of Atlantic posted this item: http://politics.theatlantic.com/2009/04/when_an_emergency_is_an_emergen… in which someone emails him to let him know that when HHS declares a public health emergency, it's a legal thing, and not a panic-in-the-streets-thing. Well, no shit. But here we have a political beat guy blogging about public health, as well intentioned as he may be, and just missing the language.

To me, the fact that only 1 of 40 cases was not actually IN the affected region of Mexico is pretty important. Right now, secondary cases seem to be small, but are they? That's the critical question. Getting some sort of bead on R0 seems more important than running off an international tally of numbers.

Related: when almost all of your cases are travel-related, is it all that surprising that the age distribution doesn't include babies or the elderly? No, no it does not.

When you know it's easier to identify clusters than sporadic cases, and 28 out of 40 cases are part of an easily defined cluster, and those 28 are in high school, it is meaningful that the median age is 16? No, no it is not.

At least not yet.

If that is true, it would be wonderful! Still not great, but better than 'it'.

I completely agree that the WHO response to this outbreak has been hesitant and inadequate, and that there is absolutely no correlation between the current WHO pandemic phase of 3 and the reality on the ground around the world. However, the US Gov. is clearly engaging in the same kind of head-in-the-sand approach to classifying this outbreak as the WHO. After all, we're still at 0 on the Federal Response Stage! And this attitude is clearly being influenced by guidance coming from the very top. What kind of message does it send to your top national health officials (to the extent that we even have permanent top health officials at the moment) for our president to go golfing for the first time in his presidency on the very day that a national public health emergency is declared? I am a big democrat and was an early partisan of Obama who supported him throughout his campaign and presidency but I'm pretty disheartened by his approach to this problem. I fear that this may turn out to be his Katrina moment. I fervently hope that this outbreak is as harmless as it now seems to be in the US, but I fear that the present lack of deaths here is just a result of the small sample involved. Even with a very high case fatality rate of 2%, it would not be completely unexpected to be still awaiting for the first death out of 40 patients (and yes, I know CFR is a ratio but the term used in many textbooks is case fatality rate and it's how I learned it in school).

According to several sources, WHO has now officially moved to Phase 4.

http://www.who.int/csr/disease/avian_influenza/phase/en/index.html

"Besser said, in answer to a question, that CDC was working with USDA on evaluating the role of hog farms, if any."

This is the emerging paradigm shift; from looking at the symptom towards exploring the cause and dealing with the root of problem.

Mike: We need to know the medical profile of this travelers who got the virus, how many got vaccinated or got the usual human influenza this past flu season, not just their ages. Also, where and when in Mexico they stayed. Specially important (as you mention the secondary cases) is knowing if the people in Scotland that has symptoms and got in contact with the two infected travelers really have the virus, since apparently they are 7 of 22, that's pretty highly contagious

Uh ... so I traveled in Mexico Mar 20-29. I don't usually get sick, but in Oaxaca, a day or two after leaving Mexico City, I got suddenly ill with symptoms (extreme "chills", lethargy, head ache, loss of appetite) that match nearly exactly those of swine flu.

I'm fine now (near as I can tell) -- but should I do anything? Is there some body to whom I should report ...?

WHO has just moved up to Phase 4. As discussed before this may change again upwards. If confirmed transmission is occuring in the US and then if cases are confirmed in New Zealand or any other country and transmission is occurring there it could quickly escalate to phase 6. see definitions http://www.who.int/csr/disease/avian_influenza/phase/en/

This is a significant move, and I think that is why the WHO have been reluctant to make it, but in my view it was necessary and could have been done earlier.

Leo: I recommend you go to your local hospital for testing. It could help the epidemiologists to know if you contracted the virus and recovered. Have you had, prior to your Mexico visit, some influenza-like symptoms this winter season or have you been vaccinated? Did you travel alone and come back as the only one who had mild symptoms?

Well, I can answer one of my own questions, just found this on Recombinomics site:

"Sequence analysis of the virus from the United States and Mexico indicate the virus is the same. However, there are small regional differences. The CDC has promptly released sequences from California and Texas (see list below), and these differences allow the Texas isolates to be distinguished from the California isolates, and the California isolates also formed distinct subgroups.

The prompt release of these sequences by the CDC is commendable, and more releases are expected. These sequences will help determine differences in the more severe cases, or differences that appear as the virus spreads across the globe.

Virus Collection date
A/California/06/2009 41F 2009-04-16
A/California/09/2009 7M 2009-04-15
A/Texas/05/2009 16M 2009-04-15
A/Texas/04/2009 16M 2009-04-14
A/California/07/2009 54M 2009-04-09
A/California/04/2009 10M 2009-04-01
A/California/05/2009 9F 2009-03-30"

Still would like to know ages of Mexican fatalities if anyone has break out.... if this is a commonly known fact already I've seemed to miss it , as I haven't been able to follow all the updates with my current workload.

I'm surprised that the CDC hadn't released the sequences of the mexican samples that came from fatal cases

So, in short, nothing is known? We don't yet have data on the history of this variant, whether it's in samples going back two months, or just popped up two weeks ago? We have no idea about it's prevalence in Mexico or the US?

This is a good example of why lack of transparency is a threat at all levels -- why Americans should care about poor governance in Mexico, and visa-versa.

Important thing to note about (new) WHO Level 4 definition: Prior recently raising to Level 4, WHO had to first redefine the levels. Why? If Spain had reported "confirmed" and WHO was compelled to review appropriate level BEFORE redefining, the old definition of Level 6 would have forced their hand: 'new virus, human-to-human in several countries inside one WHO region, as well as at least one country in another WHO region' (I summarise). As it was, given that MEX, USA and CAN had confirmed cases, Level 5 had been reached even earlier. Further to this, had Melbourne WHO centre had on hand the present porcine flu strain to positively test those NZ samples send to it a couple of days ago, level could have been set at 6 even earlier. The only reason it wasn't was because Melbourne could only test "negatively" against strains it held in its reference library. By now I expect Melbourne will have received from CDC or Canada samples of the present flu to positively test the NZ cases, so NZ should report "confirmed" shortly. In summary, I feel WHO is performing poorly, and this recent scramble to redefine its Levels is yet another example - watch out for increasing spin, and rewriting of history as we move forward...

frog: Not the case that nothing is known. It takes time to develop this information and people are working very hard to do it. I expect we'll have some data soon. We'll all have to be patient. That's the way it is. No one is sitting on their hands. On the contrary, there are armies of people working their butts off to provide these answers. Highly competent people.

An Australian: There was an official announcement that the NZ cases were negative

Not the case that nothing is known. It takes time to develop this information and people are working very hard to do it. I expect we'll have some data soon. We'll all have to be patient. That's the way it is. No one is sitting on their hands.

So, you are saying that, as of now, nothing is really known (with nothing being hyperbole for much less than we need to really ascertain the situation)? No one is accusing anyone of malingering. I'm just checking whether I've missed some information dump --- or if all the discussion is simply hand-waving before the real data starts arriving at some point in the future.

In short, are WHO and CDC trying to be prophylactic, or is there some real data currently available to really estimate the nature of the infection? It appears to be the former, that as of today, all we have is very rough hospitalization data and a couple of sequences, compounded by the opacity of the Mexican government on the one hand, and people's natural tendency to panic in the face of ignorance on the other.

An Australian writes: "WHO had to first redefine the levels."

WHOA!

You mean WHO just changed definitions in mid-outbreak?

I looked at:

http://web.archive.org/web/*/http://www.who.int/csr/disease/avian_influ…

for WHO's prior definitions and found nothing comparable to the detail currently available at:

http://www.who.int/csr/disease/avian_influenza/phase/en/

So it is impossible to detect any changes from the web archive history.

What exact wording did WHO change?

frog: No, I'm saying that a great deal of information is known that is being used to develop the things we need to know, like CFR, R0 and serial interval. It would be like saying nothing is known about curing cancer because we can't cure it yet.

revere:

I would agree that nothing is known about curing cancer, insofar as we can't actually cure it (except that we can cure some cancers, so the analogy is poor to start with).

You're getting stuck on professional pride. Until we have the important metrics, we don't know enough to make any predictions; aka, we're hand-waving. We can't even check whether the data we're getting is any good, until we can compare the highly contained outbreaks where we can control our data collection with the mass data coming in.

Hopefully y'all can get that data before one of two bad scenarios comes about: a) everyone is in a panic, but this flu turns out to just be a normal flu, causing mistrust; or b) this flu turns out to be 1918 nasty, but we've waited too long to act. Good luck to the epidemiologists!

I'm exhausted, my throat hurts, my nose is running, my eyes are red, and all I want to do is crawl into bed.

I hate allergy season.

( :P )

Many thanks for the update Groth. I retract what I said about NZ - Oceania remains clear for the moment. Reports in Queensland and New South Wales (states of AUS): 15, NIL confirmed as at approx. 23:00 UTC/GMT 27 April 2009 8.30am 28th our time).
Is there any estimate of time when we will know a) how easily this thing spreads and b) how it effects those it infects? Secondly, any more news on why USA/CAN cases so mild cf. MEX?

Revere, you posted some great explanations a couple years back about the biology and genetics of flu viruses and what affects virulence.

It would be great if you could provide links for those interested in a refresher.

The big questions many are asking are:

1) Can a virus that is genetically identical cause generally mild symptoms in one population and very serious/fatal symptoms in another? If not, what are the possible explanations for the current picture.

2) Lots of speculation that this must be a genetically-engineered sample that escaped/was intentionally released from some lab, because of the genetic fragments from swine, bird & human flu. I recall from the H5N1 discussions that this was not unusual from flu viruses, despite much debate about the mechanisms, but forget the reasons why.

I wonder if you might consider addressing those questions for us lay folks.

Is there a virologist here who can clarify whether a person with the "swine" flu can contract avian flu when exposed to infected chickens? If so, does that combination enable the infected person to transmit avian flu to another human? If so, would it matter whether the other human also had "swine" flu?

this has been bothering me since yesterday. are autopsies and tests being done in US on all fatalities from flu-type illness in the last 2-4 weeks? have instrux been put out to pursue such autopsies ongoing? if a flu is capable of killing (and what population?), and/or the mexico virus has gotten into US undetected already, wouldn't such autopsies be a good way to find out?

or is it the case that there simply have not been any flu fatalities in US recently of people not normally vulnerable--unlike the case in mexico? and that even 1 or 2 such would have been noticed and reported here?

Lisa the GP: I must have checked my temp 10 times this weekend even though I knew damn well it was allergies:) Don't know about everyone else, but I'm not seeing any additional bad news. Just repeats of the same old stuff.

Reveres:

Please keep making succinct, epidemiology-oriented, insightful posts like this one. I am in a position to pass good web articles on to very highly placed HHS officials, and I generally pass yours along (Sunday sermons excepted). Those people, and a bunch of others, carefully read posts like today's. Keep it up! It's incredibly helpful to have smart people boil down the important epidemiology in this breaking event.

I smile every time I think of Henry Niman unilaterally raising the phase straight from 3 to 6.

I almost hesitated to post this question because Doug's last comment seems like such a good closer. :)

"Name", above, made a general request for information on the subject of virus genetics. I have a similar, but more specific, question:

When "they" say that the virus signatures from both Mexico and the US are essentially the same, I'm assuming that they are referring to specific genetic markers and patterns that are already known. Is it possible, however, that we don't currently know *all* of the possible genetic markers for flu behavior, that there may be some which we haven't identified yet?

Worse, do the known genetic markers change over time as viruses mutate, such that new genetic markers come into existence, or those previously identified disappear?

It's very difficult for us "lay public" to really understand this whole situation, because, without information like that above, and the training to understand it, we only get a very fuzzy picture of the truth. (Yes, I'm now lamenting that I didn't pay more attention in biology class. :(

grothendieck: I haven't been vaccinated this year. I don't think I'd had any flu-like symptoms, but I seldom (once every five years?) get sick the way I was in Mexico.

My travel companions didn't exhibit any symptoms -- it was just me.

Did I mention I live in San Diego?

Great coverage! One fault: be care with your use of "its" and "it's." I know, it's picky, but I'd want someone to tell me too :)

MildSkeptic: Your points are on target. We have talked here often about how we still don't have enough knowledge to predict the biology on the basis of the sequences (e.g., what makes transmissibility or virulence). In some cases, like host or organ specificity there has been a lot of work (receptors) and we have some solid ideas but there remain many unknowns. And there are always tiny differences in isolates, most of which are of no biological significance. But we can't be sure we know all the tiny changes without biological significance, so whenever I hear CDC or WHO say the viruses are "genetically identical" I wonder what they mean, exactly, especially when CDC says they haven't compared everything (and again, I don't know if they mean all the isolates or all the segments or what).

There is a lack of clarity about the genetics, with US sources saying the segments are sine, human and avian while WHO saying just swine. CDC is curiously reticent to clarify this when asked.

Ames: It's a peeve of mine, too, and I try to catch them all (when typing fast and thinking as fast as I can it's remarkable how the two can get mixed up because they are homonyms). So I'll try to get them all. But I'm petty tired. But your point is well taken.

Revere: I have a speculation about the different CFR between Mexico and the United States, I have no evidences on this speculation; it is based on my experience in shrimp resistance to viral infections and related research.

I guess that the virus has been originated from the United States for a while, perhaps has circulated a decade or more in the United States, and it has caused seasonal flu sometimes. This virus is not tropical type, and it has been introduced by human or swine to Mexico lately. The pig farm with huge numbers was the first incubator and it was permeating from the farm and infecting people.

If the people in Mexico who have never traveled to the United States and their immunity are naïve to this virus, then the CFR are higher than the patients who are long time exposed to this virus.

Therefore, the record of the infected patients who died had lived/ or not in the United States could be a clue to compare. Later the sequencing and molecular evidence maybe can tell the possibility.

If this speculation is relevant, then the vaccine that used to protect the American patients would be a right hit for Mexicans to prevent the infections. And it will disappear when the climate becomes hot.

Please forgive me to comment by this speculation; it is only an instinct, no scientific evidences.

Thanks for this. I'm glad to see I'm not the only one who thinks the WHO is hurting its credibility by downplaying the situation. As I was just mentioning on my blog (panfluwatch.blogspot.com), we actually meet the criteria for Phase 5 as currently defined by the agency, itself:

"Phase 5 is characterized by human-to-human spread of the virus into at least two countries in one WHO region. While most countries will not be affected at this stage, the declaration of Phase 5 is a strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short."

With the outbreak in Mexico plus the laboratory-confirmed human-to-human transmission from husband to wife in Kansas, there's no way the WHO should be calling this Phase 4. Do they think we can't read?

I participate in to the WHO live teleconference briefings, and at last night's briefing (where they raised to level 4) Dr Keiji Fukuda, Assistant Director-General ai, Health Security and Environment stated in response to a question that, basically it's too late to stop/curtail border crossings and air traffic. The questioner from Science Magazine pointed out that the Harvard study of a few years ago showed that, although a 'flu' spread might indeed be inevitable, the point of controlling human traffic and quarantining people was to 'buy time' for vaccine development. I was taken aback by the WHO's comment in this context.

James: As I recall that study (a modeling study) the indications were that the delay would be small and not enough to allow a vaccine to be prepared, although perhaps enough to allow systems to get ready. OTOH, like all modeling, it had some very specific assumptions that may bias things in one direction or another and didn't take into account the risks of restrctions on borders and travel (e.g., delay in moving essential people, goods, services and encouraging covert scattering to escape the controls and/or confinement to a region). This is from memory, but the reporter was operating from memory, too. I think WHO's take is in line with the thinking of the public health community (BTW, I am a strong advocate of modeling and if you click "antiviral model series" in the sidebar you will find a series of 17 posts explaining a single flu model paper; but models must not be made to bear more weight than they can endure, and this is an example of that, IMO).

An Australian writes: "Prior recently raising to Level 4, WHO had to first redefine the levels."

Is there a URL to the prior definitions?

This may shed some light on the question why mortality rate in the Mexican cases is so high compared to the US and other countries. Here in Mexico, self-medication is a common practice. Going to the doctor is, at least for most of the population, impractical: long queues and many waiting hours are the rule in every government-operated hospital or clinic, and most of the people prefer to self-medicate instead.

The infected people may have done this, masking some of the symptoms, and ending up heading to the hospital when it was already too late for the antivirals to be effective.

This is purely speculation, of course. Unfortunately, our authorities haven't released any information on the victim's profiles (except for the age range), so it's hard to know if sanitary conditions or other health conditions besides influenza have been a factor.

"This is purely speculation, of course."

Roland,

I've read some comments on New York Times from the people in Mexico. Their speculations are something like this; if the people got infections directly from the pigs, their mortality rates are very high. Whist, if their infections are H2H, then their mortality rates are low.

This speculation will explain that Americans perhaps were H2H infected cases therefore no mortality so far. What do you think?

"This is purely speculation, of course."

Roland,

I've read some comments on New York Times from the people in Mexico. Their speculations are something like this; if the people got infections directly from the pigs, their mortality rates are very high. Whist, if their infections are H2H, then their mortality rates are low.

This speculation will explain that Americans perhaps were H2H infected cases therefore no mortality so far. What do you think?

Thank you, Revere, for your response (#44, above), which actually makes this much clearer for me -- especially:

"...so whenever I hear CDC or WHO say the viruses are "genetically identical" I wonder what they mean, exactly, especially when CDC says they haven't compared everything..."

I think that a description of "high correlation" would be more accurate than "identical", and make much clearer the high degree of uncertainty that it seems we still face when trying to identify and define viruses.

This, in no way, undermines the incredible work that can now be done in this area, and how the knowledge we do have, at this time, can give us a big leap forward in tracking new viruses compared with the past.

On the contrary, I think it instead highlights how enormously complex this work is and indicates, at least to me, that y'all should get more credit for this work. In fact, I think that right about now is a good time to start asking for some extra "perks" -- personal Lexus perhaps? ;)

Paiwan,

there's a lot of misinformation and speculation going on in here right know. There are all sorts of theories flying around, and the fact that our authorities don't release much information doesn't help. For example, there's a lot of people lying the blame on a pig farm in the eastern state of Veracruz, when it isn't even a proven fact that the virus actually came from pigs.

As for what I think? Well, I don't know what to think anymore. But the fact that there are huge differences between the American and Mexican health systems and infrastructure may be a factor. When people here get ill, they usually self-medicate or take some homemade remedy, and will only see an actual doctor if they haven't recovered after a few days. And those few days may have been a difference for some of the people who have died.

A Mexican toddler died in the United States:
http://www.nytimes.com/2009/04/30/health/30flu.html?pagewanted=1&_r=1&hp

Presumably the baby had been taken care of/treated by the American medical system? The question of why died ones are only Mexican patients deserves further investigation.It may serve a clue to the epidemiological discovery of swine flu.