Effect Measure

One of the things we’d like to know about the swine flu virus is its Case Fatality Ratio (CFR, commonly called a case fatality rate, although it isn’t technically a rate but a proportion). But what is a CFR? And how is it different from a mortality rate?

The CFR is an estimate of the probability that someone with the swine flu will die of it (technically, before dying from something else or recovering). The higher the CFR, the more virulent the virus. So what’s virulence? Virulence refers to the severity of the disease the virus produces. Rabies is a virulent virus. Everybody dies from it once they start getting symptoms. Rhinovirus infection (common cold) isn’t very virulent. We use CFR here to describe how virulent this virus is.

That’s a little too simple, though, because disease, whether virulent or not, isn’t just about the virus but it’s about the virus and the host relationship. The virus uses the host to make copies of itself by hijacking the host’s cellular protein making machinery for its own purposes. If it can do this without much cost to the host, that’s fine. That’s why the some viruses are able to co-exist happily with their hosts. Many birds are infected by influenza viruses without any apparent ill effect. The very same virus, however, might kill us. That’s a different kind of host parasite relationship. Virulence isn’t something inherent in the virus but a function of a host – virus combination. That’s one reason why we can’t tell how virulent a virus is by just looking at the virus. We need to know its biology in the environment of our bodies.

One observable measure of virulence, then, is the CFR, which brings us back to the question: what is CFR? Again, in simplest terms we can estimate it by using as the numerator the number of swine flu deaths in Mexico (or the US) and divide it by the total number of cases. That proportion is an estimate of dying of swine flu. Simple. Unfortunately a little too simple, because we have great difficult ascertaining both the numerator and the denominator.

The numerator, ideally, would be everyone who died of swine flu. To do that we’d have to have a strict definition of a swine flu death, for example, someone who died of respiratory failure and had laboratory confirmed infection with the swine flu virus (don’t give me grief about the definition; it’s just for illustration). Does that cover everyone who died of swine flu? What about people who didn’t die exactly that way? What about the accuracy of the test for swine flu infection? Do we even have a tally of all the deaths? Have they all been tested, or were some buried or cremated before testing?

In a sense the numerator is the easier part. The denominator is meant to tally all the swine flu infections. Not just the hospitalized cases, not just the symptomatic cases. If you really want to know the risk once infected, you have to have them all. That could be a lot of people, too many to get specimens from and send them to Atlanta. Many people probably never see a doctor and ones that do don’t get a specimen, and of the specimens some get lost or misplaced or degrade, and the lab may make mistakes. So you are likely to miss many cases. But without laboratory confirmation you are also likely to count many people who are sick with other viruses, which are prevalent at any time of year. Think about your city during flu season. How would you go about figuring out the total number of people who had flu? Once you start thinking about it you begin to see the difficulties.

If you undercount the denominator you falsely inflate the CFR. That’s almost certainly the case when you try to estimate CFR in Mexico by dividing number of deaths, 140 (only 20 of which have been laboratory confirmed), by the number of suspect cases (1640 or whatever the number will be when you read this). But you might overcount the denominator, too. There are a lot of viruses that produce “flu-like” symptoms. That would underestimate the CFR.

So what’s a mortality rate? A swine flu mortality rate is the number of deaths divided by the population at risk of dying. The numerator is the same (number of deaths from swine flu; a time period should be specified) but the denominator is now all the people in Mexico City. CFR is a proportion, a number between zero and one. The mortality rate is a number of deaths in some convenient unit of population, say number of swine flu deaths per 100,000 people. It is a whole number between zero and 100,0000 (hopefully not, because that would mean it wiped out the whole city). These two numbers are telling us different things about the virus. A mortality rate is easier to calculate because the denominator is easier to estimate, using census information, but doesn’t reveal virulence, so CFR is what is interested in this case.

We’ll discuss other basic measures and principles as this wears on. After all, there is only so much you can say when there isn’t much new to report beyond new cases. It’s something to do until we get more scientific data. And when we get it, we’ll all be on the same page.

Comments

  1. #1 Russell
    April 27, 2009

    I suspect the denominator in this situation is way, way under-counted. Most people who get an ILI aren’t going to see any medical professional. Which doesn’t mean the hospitals won’t be swamped with people who have everything from a cold to a sore throat thinking they have this flu. Unfortunately, an individual’s tendency to seek medical care has as much to do with their own individual psychology as it does with the disease they have. ;-)

  2. #2 Dean
    April 27, 2009

    Thank you for teaching whoever is interested.

  3. #3 Rock
    April 27, 2009

    Is it still believed that the CFR for the 1918 flu was 2% ?

    Also, has anyone released information on the genetic similarity between the current flu strain and the 1918 strain?

    Thanks to anyone who answers.

  4. #4 Jack
    April 27, 2009

    The CFR for rabies is close to 1, but it’s not all the way there. There’s been at least one case where the patient survived. I suspect that the ratio will go down now that doctors know what to do.

  5. #5 John Donson
    April 27, 2009

    In late winter/early spring, a nasty upper respiratory bug made lots of people, young and old, sick in central Vermont. At the risk of sounding xenophobic, which I am not (merely a truthful observer), central Vermont is home to a large population of Mexicans, who work on many of the dairy farms.

    Is it possible that the “US” form of the disease (mild as in the NY school cases) was the culprit? Anyone have any thoughts on this?

  6. #6 chivitopelon
    April 27, 2009

    for the second time in 3 years, im moved to post:

    revere–thank you for your generosity of spirit in continuing to provide the most credible, most scientific, most detailed and least varnished information to all of us and, further, for engaging with each of your students here to clarify any point when asked.

    “The secret of education lies in respecting the pupil.” – Ralph Waldo Emerson

    you are clearly a humanist, a realist and, i dare say, an optimist.

  7. #7 Phillip Huggan
    April 27, 2009

    THEY ARE DYING IN MEXICO CITY BECAUSE OF THE ELEVATION:
    http://www.ncbi.nlm.nih.gov/pubmed/15581198
    I dunno, maybe it is the elevation that causes low humidity. Elevation makes pneumonia more deadly. Mexico City and San Luis Potosi have high elevations. Not so much Baja Mexico and IDK about Oaxaca, but the majority of deaths are Mexico City.
    The origination in Mexico is a complicating factor, but people aren’t dying because they are Mexican, they are dying because they live at high altitude. These cities would be most at risk if global Swine Flu outbreak: http://www.trivia-library.com/a/10-highest-elevation-cities.htm
    The severely sickened women in California with a weakened immune system developed diarrhea but *not* pneumonia. If she lived at altitude I bet she would’ve died.

    Still corrollaries with first Spanish Flu wave so want vaccine and want to wipe out this weak “wave” and/or animal reservoir ASAP to avoid replaying fall 1919 second wave.

  8. #8 revere
    April 27, 2009

    Rock: This is one of those numbers that gets repeated over and over (I’ve done it plenty) but when you look for the source it’s often secondary source in the seventies or eighties. I think the unpalatable truth is that most estimates about deaths in 1918 are unreliable. If there were 100 million deaths with a 2% CFR then there would have been 5 billion infected in a world population of 1.8 billion in 1918. Even 50 million doesn’t work. In fact 20 million would mean half the world was infected at 2%. Not credible.

    Current sources seem to fudge this a bit and use a figure of >2.5%. That leaves a lot of room. One of our loyal commenters here, Dylan, once raised this point with me when I used the 2 – 3% number uncritically and if I recall made a fairly credible estimate of somewhere between 8 and 18% CFR. 10% sounds sort of reasonable to me. But truthfully I don’t know and nobody knows. We don’t know how many people were infected nor do we know with any plausible accuracy how many people died.

  9. #9 tcoreyb
    April 27, 2009

    That’s true, Phillip. Mexico City has a number of factors that could make the infection more dangerous. Altitude (affecting humidity and the respiratory system), aridity (partly latitudinal, partly altitudinal), and high pollution being the 3 main factors I can think of.

    Add to that a sub-standard health care system (not saying that ours in the US is world class itself :) and a slow official response (likely to happen almost anywhere, cf. Katrina), and that could easily magnify the incidence of secondary infections and death rate from pneumonia, etc.

  10. #10 Phillip Huggan
    April 27, 2009

    tcoreyb hopefully we won’t have to find out whether it is air pollution or altitude that kills.

  11. #11 david m
    April 28, 2009

    While we may not be able to extrapolate virulence, CFR, etc from the complicated evolving situation in Mexico, can’t the St. Francis Prep School in Queens provide us with some crude guideposts? i.e. — how many students went down to Mexico? how many of those students got sick…and how sick? how many students have serological evidence of infection without clinical symptoms? Of those who were secondarily exposed at the school…what was the infectivity rate? Pretty easy to get answers to these questions…..

    Oh…by the way…do we know whether the strain in the US cases is EXACTLY the same as the strain in Mexico?

  12. #12 glock
    April 28, 2009

    If I heard correctly watching Charlie Rose tonight, Laurie Garrett said that this current novel swine flu was picked up 1st in Texas and then California early this past fall, making it homegrown and not entirely a Mexican import.

  13. #13 jon
    April 28, 2009

    Sacramento count now up to three students confirmed

    http://www.sacbee.com/topstories/story/1815151.html

    Curiously, a fourth student, who had traveled to Mexico and showed symptoms of the virus, tested negative.

    Which raises a question I haven’t seen addressed yet — how reliable are the tests? 80 percent? 90? Or better? Anyone know?

  14. #14 Brian Geers
    April 28, 2009

    Why have we not heard the term “Tamiflu Blanket” yet? It surprises me that the use of Relenza and Tamiflu hasn’t been discussed. This could explain why the US would have a lower CFR compared to Mexico,at this point. I’m guessing these initial outbreaks are being showered with antiviral’s which Mexico was lacking initially.

  15. #15 BrianC
    April 28, 2009

    Is this a newly evolved virus or is it merely a newly ‘detected’ virus. More specifically, how do epidemiologists know when a new virus first developed?

  16. #16 maryinhawaii
    April 28, 2009

    The same uncertainty for the number of cases infected (denominator of cfr) exists for all pandemics, epidemics and outbreaks. So if we assume a similar proportionality of uncertainty, we could extrapolate that relative to the 1918 pandemic rate of 2.5% cfr this current Mexican epidemic has about 3 times the cfr. Would that be a valid assumption?

  17. #17 Pork Flu
    April 28, 2009

    I would have thought Denver, CO would have been hit already since it is a little bit like Mexico City. It has high altitude, pollution, and a large Mexican population (people travel back and forth to Mexico a lot from Denver).

  18. #18 Paul
    April 28, 2009

    chivitopelon posted: “revere–thank you for your generosity of spirit in continuing to provide the most credible, most scientific, most detailed and least varnished information to all of us and, further, for engaging with each of your students here to clarify any point when asked.”

    I would like to hardily second that salutation to you, revere. You are a patient and kind teacher, and you attract a group of posters who are also generous in teaching the others who come here for answers.

    An additional comment on the deleterious factors attributed to high altitude, we need to include decreased atmospheric oxygen – greatly affects oxygen tension in the blood with compromised pulmonary function (in this case, from disease).

  19. #19 pft
    April 28, 2009

    Most people who go to hospital and get tested have complicated flu, ie, severe symptoms. Those without symptoms or having mild symptoms, especially otherwise healthy adults, just stay at home. They go uncounted. The denominator is the number that is likely to be vastly understated. I don’t see it ever being over counted unless all infections led to severe infection and there was no test to determine the cause.

    SARS was a good example, it turned out there was a large population who were asymptomatic or showed mild symptoms. I believe I may have been one of those, infected before SARS was public knowledge, probably in Shanghai or Hong Kong. I was never tested though.

    SARS tended to affect Asians more seriously. This flu seems to affect Mexicans more seriously, but it is too early to tell. Given our large immigrant population, the lack of fatalities in the US would suggest better treatment of patients with complicated flu.

  20. #20 doc H
    April 28, 2009

    Many of you are getting way off topic with altitude theories and just adding noise to confusion. This type of info is very un-helpful!

  21. #21 revere
    April 28, 2009

    maryinhawaii: No, that wouldn’t be the case. The 1918 number is very unreliable (I discussed it in some thread or other but it’s 3 am here and I’m too tired to hunt it up) and estimated from data very unlike these data. Also CFR differs in different subpopulations and regions. If it is the virus we are comparing we want to compare like with like. It’s very messy. So comparing with the several 1918 CFRs is not a good idea, IMO.

    pft: I’m not aware SARS was worse for Asians than non-Asians.

  22. #22 Lowlander
    April 28, 2009

    Actually there are now 2 described cases of survival to rabbies after developing clinical symptoms through the so called Millwalkie (pardon the spelling) protocol.

    Revere: Are pig livestock units in the US subject to any Influenza surveillance programme? In the UK there is suposed to be one in place but since it is voluntary, it basically only works in units working for the export market.

  23. #23 FranzHessel
    April 28, 2009

    Nice Blog, lots of interesting information.
    But regarding CFR I am missing one point:
    The nominator and the denominator belong to different moments in time. In short: The number of people having the virus at time T will develop symptoms earliest at time T+x1 and all related casualties will have happened earliest at time T+x2. Now the nominator should be picked from T+x2, while the denominator should be picked from T. In reality, both numbers are usually stemming from the same time (and thus the denominator is being overestimated, probably a lot, because the infection happens exponentially).
    By the way, does anybody know the incubation period of the virus?

  24. #24 suzanne bunton
    April 28, 2009

    Doc H: Actually, i was glad to see the altitude theory comment, and had to force myself to refrain from thanking Phillip for it, to keep the noise down. (Instead i looked up the altitudes of all the cities where there have been deaths–and they are high). Sometimes the slightly off-topic comments here provide very welcome answers to questions on the minds of many readers of this forum.

  25. #25 Dylan
    April 28, 2009

    “By the way, does anybody know the incubation period of the virus?” Franz

    Latest estimates, that I am aware of, put it in a time frame of 24 to 48 hours. Very short incubation period. It seems that it is out in the body very quickly, after initial infection. Revere can address the implications of this, with respect to immune system response, etc. Brings up a lot of peripheral questions, of course; why do people not present before they return from a two week trip to Mexico, for example? Or do they? And the symptomatic period seems to be fairly lengthy, at least with the generally mild cases. The severe cases seem to move from first expression, to something approximating systemic collapse, over roughly six to eight days, from what I can tell. From what I have read, they begin to fail around the third day after the first expression of full symptoms, and they die around the fifth day beyond that. Everybody simply cannot be catching this thing in the Mexico City airport, can they? I think that Mexico City is steeped in this thing, now. Possibly far more than we suspect. If so, that is probably a good sign. At the first indication that cases and deaths have entered a declining phase, we will have some idea of where we are at. If this was 1918, the streets of Mexico City would be hip deep in dead bodies, by now. My hometown, in Illinois, with a population of roughly 40,000 in 1918, suffered twice the number of influenza deaths in October, 1918, that Mexico City has acknowledged, to this point.

  26. #26 revere
    April 28, 2009

    Franz: Your points about estimating CFR are exactly right. This potential bias was considered in the SARS case and is also a general one with surveillance data. In effect, the data are right censored because we don’t yet know the outcome for all of the denominator (the time difference isn’t the exact problem because we want to consider some final cumulative incidence number but have yet to stop cumulating the denominator). Some methods for correcting this bias are available but require assumptions, of course. But nice pick-up.

  27. #27 Russell
    April 28, 2009

    It seems to me that the infection rate could be estimated pretty well after the outbreak is over by asking a random sample of people in the population under study to allow anti-body testing. Is this ever done? Or are the anti-bodies for flus too generic to pin down to specific variants?

  28. #28 revere
    April 28, 2009

    Russell: No, this would likely be the way it will be done at some point. Neutralizing antibodies for the strain should be fairly specific. That dosn’t solve the “now” question that everyone is asking, of course.

  29. #29 MarketBlogic
    April 28, 2009

    There’s another way of estimating the CFR that isn’t being used that is start to make me question whether this new strain of flu is anywhere close to being a virulent killer: look at the TOTAL flu-related or pneumonia deaths in Mexico in an AVERAGE YEAR versus the TOTAL flu-related or pneumonia deaths THIS YEARS.

    If you proxy Mexico by using CDC data for the U.S. and then divide crudely by three (US-pop is 300+ mil. vs Mex-pop of 110 mil.), you come up with something like 1,000 Mexican deaths from flu-related illnesses per month in an average year and maybe 20,000-40,000 pneumonia-related hospitalizations per month. None of the statistics coming out of Mexico are very reliable, but considering that there are 110 million people in country and 20-25 million in Mexico City alone, I don’t understand what the panic is about given the very small number of confirmed cases thus far — if there are huge numbers of unconfirmed deaths and hospitalizations that would be different, but other than a pretty unreliable message board at a BBC website with lots of anecdotal stories I haven’t seen much of anything.

    What am I missing here?

  30. #30 Patch
    April 28, 2009

    Brain Geers,

    The tamiflu blanket..

    One thing I have not seen mentioned much on media reports is the administration of Tamiflu for the US cases. That would certainly effect not only CFR, but virulence too, wouldn’t it Revere?

    I saw an interview on CNN of one of the high school kids with it and she said before she knew what she had, she was sick enough to go to the hospital (hospital verses a “clinic” is what she said. In our area, we would go to a clinic). At that point, she was tested and given Tamiflu.

    It concerns me, that they keep suggesting a difference in virulence from the Mexican strain, without mentioning what treatment, if any, was administered.

    It concerns me, because if we either run out of Tamiflu, or more likely it develops a resistance first, we would see similar CFR. Perhaps we will anyway, once the numbers get statistically significant.

    I would also like to know what treatment (if any) the Mexican cases are being given. Are they using Tamiflu? Are they trying anything novel, ,like steroids, statins or even alternative treatment (Elderberry). Are they seeing cytokine storm or secondary pneumonia as the primary cause of death.

    Would any of that be helpful Revere?

  31. #31 Erwos
    April 28, 2009

    I would think that the use of antivirals for treatment is being deliberately under-reported for public safety/health reasons. Remember the avian influenza panic a few years ago, and the Tamiflu hoarding insanity that went with it? Last thing that’s going to be helpful is a new round of that.

    The disparity in CFR between the US and Mexico is fascinating, to be certain.

  32. #32 revere
    April 28, 2009

    Erwos: I see no evidence that this information is being withheld. Tamiflu treatment is not very common in the US, although clearly now it will increase.

  33. #33 Patch
    April 28, 2009

    Revere,

    After the CNN interview, I wondered how many of the US cases involved administering Tamiflu. Do you have any indication of it’s use? Wouldn’t that account for the difference we are seeing between Mexico and US cases?

  34. #34 Jason Dick
    April 28, 2009

    In a sense the numerator is the easier part. The denominator is meant to tally all the swine flu infections. Not just the hospitalized cases, not just the symptomatic cases. If you really want to know the risk once infected, you have to have them all. That could be a lot of people, too many to get specimens from and send them to Atlanta. Many people probably never see a doctor and ones that do don’t get a specimen, and of the specimens some get lost or misplaced or degrade, and the lab may make mistakes. So you are likely to miss many cases. But without laboratory confirmation you are also likely to count many people who are sick with other viruses, which are prevalent at any time of year. Think about your city during flu season. How would you go about figuring out the total number of people who had flu? Once you start thinking about it you begin to see the difficulties.

    This sounds like an argument for a randomized population survey. Statistics to the rescue!

  35. #35 ellie
    April 28, 2009

    Patch: This is only anecdotal evidence from one source, however this NY Daily News article indicates that in a family of 5 who got sick, only one family member, who is diabetic, was given “preventative medication”. I’m sure you can’t extrapolate what’s happening throughout the country from this one story, and NYC has some of the best doctors in the country who might be aware of the danger of overuse of Tamiflu and are thus using it sparingly. But its information nonetheless.

    http://www.nydailynews.com/ny_local/2009/04/28/2009-04-28_queens_family_of_five_has_swine_flu.html

  36. #36 Phillip Huggan
    April 28, 2009

    “Which raises a question I haven’t seen addressed yet — how reliable are the tests? 80 percent? 90? Or better? Anyone know?”

    When they get sent to CDC Atlanta or Health Canada Winnipeg Labs, they are 100% (the NY school cases take 6 days to confirm this way).

    “What am I missing here?
    Posted by: MarketBlogic”

    It was the initial unknown (and still unknown) death rate in Mexico that people were extrapolating to the world when this went public Apr/24 until about Apr/26 when it became statistically clear there weren’t (at least significant amounts of) deaths outside Mexico or even pneumonia. 2nd, healthy demographics were being killed in Mexico, like in 1919. 3rd and still very troubling, we don’t know how the Spanish Flu spring “mild” 1st wave relates to subsequent waves of carnage. On the bright side that was Avian Influenza and this is (mostly?) swine flu, the latter typically exhibiting milder symptoms.

    “I would have thought Denver, CO would have been hit already since it is a little bit like Mexico City”

    It is clear to me they are dying in Mexico of pneumonia, not from any novel flu strain idosyncracies. If the altitude (low humidity is related but not an entirely overlapping subset of cities) hypothesis is correct it would be cities like Denver at risk once/if travellers from Mexico spread flu. If wrong it is almost certain some form of environmental (airborne chemical unless smokers and asthmatics exhibit higher death rates I assume) pollution, according to a 1984 medical self-help book I referenced. In that case many 3rd world slums at risk.
    Probably there will be some index of lung factors that combines these factors, but one will probably be most important.

    “Is this a newly evolved virus or is it merely a newly ‘detected’ virus. More specifically, how do epidemiologists know when a new virus first developed?”

    IDK but in this case a cotton swab sample from a four year old boy was kept in refrigeration and thus preserved earlier this year near that controversial pork farm. In the future it would be nice to have fridges in 3rd world clinics where civil order permits. If a pork farm is an incubator (I assume they will try to track down the animal reservoir in months ahead but IDK) the industry should pay for massive surveillence and testing quality control upgrades and governments pay for diversification towards mushroom protein sources and such (give the fake meat money to Tyson Foods for all I care).

    “Many of you are getting way off topic with altitude theories and just adding noise to confusion. This type of info is very un-helpful!
    Posted by: doc H”

    Personally, my attempts to join GOARN and other flu netowrks were rebuffed in 2007. If I had more than a $50/months income (say a doctor salary) I’d buy the paper I referenced. I assume those with families and social lives will finally output some Mexico case studies around 2020. Until then, trust me (next time the experts should output real-time preliminary analysees rather than writing their doctoral dissertations). The fact that WHO changed the definitions of their Phases on the fly doesn’t give me comfort, nor does Republican blocking of a USA DHHS Head appointment and lobbying for pandemic funds to be cut, give me reason to trust a USA government influenced by Book of Revelations lobbyists.

    Suzanne, do you have the elevations for the Baja Mexico deaths and Oaxaca (my dial up hates maps)?
    The present administrative structure of Health Bodies is not good for initial on-the-fly analysis (probably great afterwards though). I think WHO’s Rapid Response blueprint has merit, but it depends upon high initial death tolls separating a novel strain wheat from day-to-day Influenza chaff. If anyone has the time, a list of cities of high elevations, low humidity, and Mexico City amounts of industrial and/or air pollution would be good. Maybe pork farm open sewage lagoons near cities is also good. You don’t get paid for it though.

  37. #37 suzanne bunton
    April 28, 2009

    Phillip,

    Oaxaca City’s elevation is 5084 meters.

    Baja California Mexico is divided into 2 states: Baja Calfornia Norte, & Baja California Sur. From what i can gather, the swine flu fatalities were in Baja California Norte, apparently near the US Border.

    The elevation of inland Baja California ranges from 300 to 1500 meters. It is traversed its entire north-south length by mountains, so there are mountainous areas in the far north part near the border.

    I am unable to find out the cities in which the two deaths occurred, or the origins of those patients. But, given the little that i can find (i think my surfing skills are poor, BTW, so someone else may do better than i have), I see nothing that contradicts your altitude explanation for the CFR differences.

  38. #38 suzanne bunton
    April 28, 2009

    On second thought (regarding the altitude explanation for the swine flu deaths-so-far), there are two swine-flu-suspected deaths in California cities with low altitude: La Mirada, and Long Beach. More wait-n-see for us speculators.

  39. #39 rpsms
    April 28, 2009

    re: # 30

    The cdc swine flu web page mentions tamiflu as a treatment option. They use the generic name Oseltamivir.

  40. #40 sff
    April 28, 2009

    @suzanne bunton: Oaxaca City is ~5000 feet (~1550 m), not ~5000 meters, which would be higher than Tibet.

  41. #41 grothendieck
    April 28, 2009

    Can someone post how the altitude theory explains that most of the reported deaths were adults and not children or elderly people? Am I missing something? Maybe someone could explain how similar are the symptoms of influenza-derived pneumonia vs the cytokine storm?

  42. #42 suzanne bunton
    April 28, 2009

    Sff: thanks for noticing that. Sorry i was careless.

    Grothendieck: I don’t think the altitude theory explains the age range of fatalities; it merely is a possible explanation of why Mexico has swine-flu deaths and the rest of the planet doesn’t (yet). However, there is no obvious contradiction. For example, it could be that altitude simply makes things worse for influenza patients, and cytokine storms (presumably) make things worse for young adult patients, and the combination in the unfortunate few who a) get swine flu, b) are young adults, and c) live at altitude is deadly.

    I think that whoever seriously works on the question of Mexico’s fatalities should take into consideration both factors–deaths tend to be in young adults, and deaths (apparently) tend to be at altitude.

  43. #43 david b.
    April 29, 2009

    If anybody has brought up the iatrogenic angle on the current Swine Flu or SARS episode in 2003 I missed it.

    In case of SARS, it became widely known that most all Canada mortality was directly related to massive doses of ribavirin – 4 grams(!) per day for four days, after an initial 2 grams per IV called a ‘loading’ dose, then followed for six days with 1.5 grams per day! ON TOP of this, corticosteroids were also given to ribavirin patients not responding well to the ribavirin. Midway through this hysteria, Canada health officials abruptly stopped the ribavirin – and deaths immediately fell off.

    Since ribavirin is extremely well known to cause fatal hemolytic anemia, it is a wonder any Canadian patient survived – and the ones that did must have had their ribavirin stopped asap. Forty-three Canadians died from “SARS” but it most certainly was the ribavirin (etc.) that killed them. In stark contrast, the U.S. medicos made the concious decision to NOT give ribavirin to American SARS cases, and there were ZERO American SARS deaths.

    In Hong Kong, Singapore, Thailand, etc., the standard treatment (like Canada) was also ribavirin, but in smaller doses than Canada. Thus, a smaller percentage in SE Asia actually died. Nevertheless, almost everybody who died was associated with ribavirin “therapy.”

    Dr. Carlo Urbani of WHO was the doctor in Viet Nam who kicked off the SARS episode (or hysteria I would say is more accurate). Terribly ironic, Dr. Urbani died of “SARS” in Thailand after his fellow medicos rushed ribavirin to give to him – he died a few days later March 29, 2003, exactly a month after the SARS panic was started.

    Two more points: First, It was never actually established that a corona virus variation was the cause of SARS. Second, but a single SARS death of in all of Europe (France) occurred. To repeat, zero in the U.S.

    As related to current Swine Flu in Mexico, it is certainly possible when complete medical papers are published that the real cause of most Mexican swine flu deaths will be of patients given such drugs as ribavirin – the treatment being the true cause of death.

  44. #44 david b.
    April 29, 2009

    If anybody has brought up the iatrogenic angle on the current Swine Flu or SARS episode in 2003 I missed it.

    In case of SARS, it became widely known that most all Canada mortality was directly related to massive doses of ribavirin – 4 grams(!) per day for four days, after an initial 2 grams per IV called a ‘loading’ dose, then followed for six days with 1.5 grams per day! ON TOP of this, corticosteroids were also given to ribavirin patients not responding well to the ribavirin. Midway through this hysteria, Canada health officials abruptly stopped the ribavirin – and deaths immediately fell off.

    Since ribavirin is extremely well known to cause fatal hemolytic anemia, it is a wonder any Canadian patient survived – and the ones that did must have had their ribavirin stopped asap. Forty-three Canadians died from “SARS” but it most certainly was the ribavirin (etc.) that killed them. In stark contrast, the U.S. medicos made the concious decision to NOT give ribavirin to American SARS cases, and there were ZERO American SARS deaths.

    In Hong Kong, Singapore, Thailand, etc., the standard treatment (like Canada) was also ribavirin, but in smaller doses than Canada. Thus, a smaller percentage in SE Asia actually died. Nevertheless, almost everybody who died was associated with ribavirin “therapy.”

    Dr. Carlo Urbani of WHO was the doctor in Viet Nam who kicked off the SARS episode (or hysteria I would say is more accurate). Terribly ironic, Dr. Urbani died of “SARS” in Thailand after his fellow medicos rushed ribavirin to give to him – he died a few days later March 29, 2003, exactly a month after the SARS panic was started.

    Two more points: First, It was never actually established that a corona virus variation was the cause of SARS. Second, but a single SARS death of in all of Europe (France) occurred. To repeat, zero in the U.S.

    As related to current Swine Flu in Mexico, it is certainly possible when complete medical papers are published that the real cause of most Mexican swine flu deaths will be of patients given such drugs as ribavirin – the treatment being the true cause of death.

  45. #45 suzyf921
    April 29, 2009

    I wondered about smoking, altitude, and pollution as factors. (Doc H, I really think altitude is not a trivial issue and definitely not a distraction from the more “important” issues. I have pretty good lungs for a 57 year old and I spent a week in Mexico City last August (for the AIDS conference) But after about 5 days I felt uncomfortable breathing and had trouble sleeping. The altitude and pollution were getting to me, and I needed an inhaler (which I bought OTC!))

    However it seems that Mexico City residents actually may have BETTER lung health than some others. I found this table in a paper by Menezes et al in the Lancet (Vol 366, Issue 9500, 26 November 2005-2 December 2005, Pages 1875-1881)
    on COPD in 5 Latin American cities.
    They report that smoking prevalence is actually lower in Mexico City than the other 4 cities. Most interesting for our discussion is a table ranking COPD rates by altitude – the gradient is unmistakable, COPD is HIGHER in lower altitude cities. Not sure the cut and paste will work well but here is the table:

    Mean altitude (m) COPD prevalence
    Crude Adjusted * White people only
    Mexico City (Mexico) 2240 7·8% (5·9–9·7) 11·9% (11·3–12·5) 12·7% (7·6–17·7)
    Caracas (Venezuela) 950 12·1% (10·3–13·9) 13·0% (12·3–13·6) 13·5% (10·2–16·7)
    São Paulo (Brazil) 800 15·8% (13·5–18·1) 14·9% (14·1–15·7) 16·2% (13·1–19·3)
    Santiago (Chile) 543 16·9% (14·7–19·1) 14·5% (13·8–15·1) 17·8% (15·0–20·3)
    Montevideo (Uruguay) 35 19·7% (17·2–22·1) 19·4% (18·4–20·3) 20·3% (17·8–22·8)
    p† 0·0001 0·0001 0·01

    The authors hypothesize that “altitude could induce a higher growth of airways relative to lung size, leading to an increased FEV1/FVC ratio. Since altitude was available only as a mean value applied to all respondents within each city, the significant association with COPD prevalence should be interpreted with caution because it is based on only five data points. We emphasise that this hypothesis arose from the data and had not been defined a priori.”

    So – not sure where that leaves us but I found it interesting. The article hints at some ethnic differences and other possible explanations. For those of you with Science Direct here is the link:
    http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1B-4HGM7BJ-1&_user=201547&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000014058&_version=1&_urlVersion=0&_userid=201547&md5=3bbb9eaef0639867c4c72ec2d6b41dc1

  46. #46 Phillip Huggan
    April 29, 2009

    “Maybe someone could explain how similar are the symptoms of influenza-derived pneumonia vs the cytokine storm?”

    IDK similiarity of symptoms but the death rates are way different. It looks like (as soon as it was discovered the strains in Mexico and California are nearly identical) this swine flu has, all else equal, the death rate of a regular flu *for now* except it doubles or triples (depending on demographics; whether young developing nation or not) because it hits 20-40 year olds who normally don’t get flu. The cytokine storm killed many of these 20-40 year olds; no one knows the numbers but if there was a cytokine storm I’d expect thousands of deaths by now if not much more.

    Suzy you are probably right. Athletes acclimatized to high elevation have an huge advantage over those just coming to play the Avalancehe or mountain climbing without oxygen. But COPD is acute bronchitis and emphysema, not pneumonia. I really wanted CDC ground crews who rushed into Mexico to report incidence of smoking and coal-mining/hog farm occupations to test hypothesis like yours. When I google the literature I get (the abstract) pneumonia causes 3x higher death rates in high altitude cities, not 3x lower death rates. Also the Monte Video and Mexico City contrast is certainly lowered by considering Mexico City is 15x the size of Monta Video and probably has smog everyday.

    I can’t even afford the scientific paper I referenced so I await someone in the media or medical community to read it and publicize it. I would expect almost every reader of this blog if given the multiple warnings Veratect gave to CDC staff, would publicize the warnings or at least not ignore them. They are using the fog of war to hide incompetance in for example, reporting to people there is no evidence of cytokine storm and COPD (analyzing for yelloy teeth and lighters in pockets of corpses is probably enough to rule this out) as cases of death. If I bet my $30 right and quadruple my winnings picking International Hockey games, I’ll buy the paper myself and report more conclusive findings. As an herbal Canadian am interested if acute bronchitis is a factor, but it doesn’t seem like anyone knows how to do things like check a corpses pockets of lighters. Probably there are some sort of liability issues (not allowed to issue less than complete, ie. timely, findings?) that are preventing well-paid staff from earning their salaries.
    Once again, they are dying from pneumonia and that is the key to preventing more deaths if/when this goes global.

  47. #47 Anthony Gattone
    April 29, 2009

    sadly, i was diagnosed with the Swine Flu not too many days ago and the doctors told me that if i didnt get to PA, where the treatment is, i would probably die in the nex few days…i cant get a flight there until the begining of next week. I was going to drive but then i realized that i didnt have a car. Once again, they are dying from pneumonia and that is the key to preventing more deaths if/when this goes global.

  48. #48 Phillip Huggan
    April 29, 2009

    Careful with the humour Anthony, you don’t want to crowd out anyone with real questions who is really sick.

  49. #49 Sarah Wedde
    April 29, 2009

    Interesting that no-one has taken issue with the statement “When they get sent to CDC Atlanta or Health Canada Winnipeg Labs, they are 100%”. Sorry but NO lab test is ever 100%. There is always type I and type II error involved! Interesting discussion here though – so can I read that there isn’t much difference between this and ‘normal’ flu except for the jumping the species boundary/new strain issues???

  50. #50 James Bowery
    April 30, 2009

    No, Sarah, you may not read that.

    There are basically 3 regimes of Case Fatality Rate separated by about a factor of 10 each:

    1) more than 1%
    2) .1% to 1%
    3) less than .1%

    We still don’t know which range we’re dealing with and, uh, like, it matters.

    All it would take is to focus on a standard sample like Mexico City hospital interns, process their swabs STAT and count the deaths so far.

    This appears to be beyond the capacity of the CDC or WHO.

  51. #51 revere
    April 30, 2009

    James: I don’t think you quite understand the difficulty. People who work in hospitals are not a representative sample of the population, nor would “taking their swabs” tell you whether they have had an infection if they are no longer shedding virus. If it seems so simple to you but not to the people actually trying to develop the information on the ground, I think it’s a reasonable supposition that the problem is on your end. Read the post about estimating CFR again.

  52. #52 Phillip Huggan
    April 30, 2009

    It sounds heartless to say but you don’t try to board a plane with Swine Flu.

  53. #53 Samantha
    May 1, 2009

    Is this most recent hysteria not the same flu referred to in this CDC weekly report on April 17th? Why is Mexico getting the blame for the beginning of this disease. “On April 17, 2009, CDC and the California Department of Public Health determined that two cases of febrile respiratory illness occurring in children who reside in adjacent counties in southern California were caused by infection with a swine influenza A (H1N1) virus. On April 22, CDC confirmed an additional three cases of swine influenza among residents of the two counties, two adults and one adolescent. All case-patients had symptoms of ILI. Additional testing at CDC identified swine influenza A (H1N1). All five had self-limited ILI and have recovered; one required hospitalization. Two additional cases were identified from Texas and confirmed as swine influenza at CDC on April 23……” http://www.cdc.gov/flu/weekly/

  54. #54 Motor Sports
    October 30, 2009

    I take a lot of Vitamin C to boost up my immune system, I think it will work for me. Some of my neighbors have flu, I am still racing the motor sports with no problem. If you take care yourself by enhancement your immune system. I believe your body can immune from swine flu.