Bird flu: how many deaths will it take 'fore we know?

The newswires are humming again with another story of the estimated toll a flu pandemic might exact, if it were as bad as 1918. This time the occasion is a paper just published (.pdf) in the British medical journal, The Lancet, which attempts the most careful estimate yet of the toll of the 1918 epidemic. As often happens, the headlines, and in some cases the contents of the articles are all over the place. Some examples: "Bird Flu Can Kill 62 Million People", "New flu pandemic could kill 81 million", and "Study Finds Much Bird Flu Planning is Misplaced." We took a look at The Lancet article and here's our take.

The authors used international mortality data from 27 countries and regions where there was a minimum of 80% death registration in the years 1915 to 1923, trying to correlate the wide variation in mortality with community attributes. By restricting their data set to these "registration areas," they are able to make more comparable comparisons between areas that differed in mortality. They selected two features of the communities that might indicate important differences, per capita income and latitude. The former is a surrogate for many factors that could contribute to differences in mortality, including access to medical care, education, nutrition and many other things that might be related to both income and the risk of dying from influenza. Comparable data are available for most countries in the world today, so any relationship might be used to make an estimate of current mortality variations from a pandemic of the same character as 1918. This assumes that the relationship between per capita income and excess mortality from influenza is of the same nature and effect as it was in 1918. The authors give some reasons to justify this assumption. Latitude is a feature of geography, in particular seasonal variation and level of temperature which some think might be related to influenza outbreak patterns. This is feature that has not changed appreciably since 1918. The correlations they derive are statistical in nature but are derived from actual data. In effect, they attempt to summarize the data in a manner that would allow some insight into why one place had a higher mortality than another. It is a task fraught with difficulty.

Previous studies have used records of "normal" seasonal variation to estimate how much excess mortality is produced by an epidemic by subtracting the normal from the outbreak period; or they have used cause specific mortality to estimate influenza deaths at particular points in time. Coding of cause of death changes over time, however, which produces additional complications. The authors of this paper elected to use mortality from all causes to avoid this problem (the fact of death is more certain than the cause of death). This also would take account of the possibility that influenza might affect other causes of death. Their data did not allow a week by week or month by month analysis, however, and they settled for annual averages. To calculate the excess of total deaths from influenza they averaged the death rates in the three years before the pandemic, 1915 - 1917, and the three years after the pandemic, 1921 - 1923, and compared these average rates to the rates in the years 1918, 1919 and 1920 (the "pandemic years"). By taking the difference in the pandemic years and the non-pandemic years on either side of them they calculated the excess of total deaths in the countries and regions where they felt the data were reliable. In some places they were also able to calculate death rates in specific age categories, as well.

One finding is not new but bears repeating. There was an extremely wide variation in excess mortality from country to country and region to region. Even within the same registration areas, for example, the Census of India, there is a 2.1% excess mortality attributed to the pandemic in Burma compared to a 7.8% in the Indian province of Berar. A 2.1% excess means that 2.1% of the population died of influenza-related causes (by this method of estimation), not 2.1% of the influenza cases. Using excess death percentages like this allows one to estimate the number of deaths that might be caused in a population of a specific size without making an assumption about infection rates and case fatality.

Using this method and some available age and sex specific data from a subset of the countries and regions, the authors were able to confirm the notorious W-shaped mortality curve for age. Here is Figure 1 from the paper:

i-c0c888be37a488cc99be151282cce9ba-Fig1Lancet_400x267.shkl.jpg

The next step in the analysis employs a statistical model to see what the effect of the two community characteristics, per capita income and latitude. One surprise is that the single variable of per capita income in a country explains half of the variation in excess mortality. This is a rather large effect of community wealth. What about latitude? The authors say in their text that adding this indicator of distance from the equator produced little effect on the ability of the model to predict excess mortality and that the effect was not statistically significant. [Small technical quibble: Examination of Table 2 in the paper doesn't quite make that case because it presents only beta coefficients, standard errors, p-values and t-statistics from two models, one with per capita income only and one with both per capita income and latitude. What would be useful for a reader paying attention would be an extra line giving the same estimates from a model with latitude only as an independent variable. The reason I say this is because it is quite plausible that these two variables, latitude and per capita income, might be highly correlated, that is, countries and regions that are in the lower latitudes might also be much poorer. This produces a colinearity and would lead to a model that is potentially unstable whose parameter estimates are highly dependent on the particular dataset. These are experienced investigators and the analysis I am suggesting is so easy I feel confident it was taken into account, but the paper is not quite complete without it. It is not the only editing lapse. The units for the latitude model are not given, so the beta coefficient is hard to interpret as an effect measure (yes, that's a real term in epidemiology!). Another complaint is that it isn't easy to see how the variance of the excess mortality was estimated, although there is some mention of the role of unexplained variance in the model. With a paper of this much importance, extra care should be taken to spell out the methodology better for non-specialists. End of technical quibble.]

In any event, the statistical model can then be used to predict excess mortality for a given population size with various age categories and per capita income as of 2004 (the latest year for which such data were available). In this way the authors toted up the excess deaths globally if a strain with the severity of 1918 were to emerge. The numbers are surprisingly high, with a median (50th percentile) of 62 million and a 10th to 90th percentile range of 51 million to 81 million. If these excess deaths were to occur in a single year, it would double the globe's mortality. Not said, the excess would pile up in a flu season, not spread out over the year. Thus the impact would be considerably greater, leading to perhaps an eight fold mortality excess over a quarter. This is an effect of catastrophic proportions. Nor is the estimated mortality logically or biologically a worst case:

In most discussions of influenza, the 1918?20 pandemic sets the upper limit, in terms of mortality, on what might occur in future pandemics. However, there is no logical or biological reason why that pandemic ?albeit very severe ? should represent the maximum possible mortality in a future pandemic. Random genetic mutation could, in principle, produce a more lethal virus, although pathogens that are too lethal might not survive long enough in the host to effectively transmit to different populations. In addition to this uncertainty about what is genetically possible, future mortality could be larger if the 1918?20 pattern of low older adult mortality were in fact due to some acquired immunity from the pandemics of the mid-19th century. (Murray et al., The Lancet, cites omitted)

But there is another, and more important, surprise. Because of the strong effect of per capita income in the statistical model (NB: a statistical model is not the same as the mathematical models we have discussed elsewhere), the lion's share of the burden of a pandemic will be felt in the developing world, by their estimate, over 95% of it. Thus less than 5% of the mortality excess will be in the rich countries, although most of the preparation for a pandemic is occurring in those countries. Sub-sharan Africa and east and southeast asia will feel the hammer blow.

Whatever the final toll, these data make a case that a source of the almost 40 fold variation in mortality seen around the world in 1918 was related in some fashion to poverty. If you live in a developed country, this might bring a sigh of relief. "They" will suffer but you won't. But most developed countries, and the United States is a prime example, is "marbled" with poverty throughout, so pockets of high mortality would also occur throughout our society. The societal "add on" of this will affect everyone in a world where we have become highly interdependent and closely connected in so many ways. Even if this weren't true, consigning most of the world to death from a pandemic is not something any government should find acceptable. It lets no one off the hook, even if one assumes you wouldn't suffer (an invalid assumption in this case).

This paper reinforces what we already "know" but often refuse to acknowledge. Whatever the analysis, the bottom line seems to be that the best way to protect ourselves is to have a robust and resilient society with an intact, effective and functioning public health and social services infrastructure. It is highly likely that the variable per capita income is a surrogate for the benefits those things bring to a community's health.

How many death's will it take before we know, that too many people have died?

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Revere-Having seen the data so far out of all the locales that have gotten it, whats your estimate of the number of people that would be saved by percentage if all things being equal, that having enough ventilators, staff to run them, doctors, meds etc, would have on outcomes?

My problem is this. Jakarta is not a slouchy little town and they so far havent had a lot of success with keeping peole alive with or w/o all of the above. Dumb doctors? I dont know. Same with the Chinese. It took what six weeks to bring a kid just out of the ICU quarantine and I think I read 2 million yuan and they did exactly what everyone else did to keep him alive. But he as major organ damage that may or may not heal.
If and when it comes do we get triaged and morphine, or will the medical science we can bring to bear on it really make much of a difference?

By M. Randolph Kruger (not verified) on 23 Dec 2006 #permalink

Randy: My view (FWIW) is that the population burden will depend primarily on the biology of the host and virus in the environmental context. It will be fairly independent of medical care. The reason I say this is that the history of diseases during the period of the modern rise in population (17th century on) has been sensitive to those things which operate on the whole community at once (e.g., clean water, food, housing), not those things which work at the individual level. This is even true for vaccines, which over the 20th century didn't seem to make much difference in mortality rates. You have to give vaccinations individually, unless you had a way to do mass distribution (e.g., in food or water or if it were a live virus that spread from person to person like the Sabin vaccine).

In other words, vents and antivirals will save some people but won't make much difference in excess deaths, IMO. A public health program of mass vaccination ahead of time if it achieved good coverage would make a difference but there isn't either a vaccine or a system to deliver it at the moment.

In order to be saved from a secondary infection with antibiotics you have to get to care, which huge numbers will not because the system will be overwhelmed. So it will depend on the transmissibility and virulence of the virus, not in our antivirals and vents.

now, the question is, why did the rich countries do
so much better ?
What can be done with money to mitigate the
impact of a pandemic ? They didn't spend it on Tamiflu
or vaccine in 1918.
Was it medical care ? But what I've read, the hospitals
were overwhelmed and most sick died at home.
Was it the home ? They had a room for the sick
and were able to avoid the sick ?
But I think the infection rate was almost the
same worldwide with 25%, or not ?

the link to the .pdf paper doesn't work for me.

anon: the link may not work if you don't have a subscription or are not a registered user. Try going to the Lancet site and doing a free registration to see if that gets you this paper. I'm not sure if it will or not.

No one knows the factors that per capita income seem to be a surrogate for. One can imagine many things that would affect survivability, including nutrition, social support, likelihood of exposure, etc. We don't know what it is or if the factors are related in the same way to excess mortality today through income.

OK, I got and read the paper now.

"Most of the strong relation that we observed between per-head income and pandemic mortality must be mediated through factors such as nutritional status,comorbidity,community characteristics associated with poverty, and the effect of supportive care, since therapeutic interventions had little or no effect on mortality in 1918-20"

---------------------------------
it should be possible to test the effect of these factors ?! Some countries presumably have reported weight of the dead and average people, community characteristics should be available and data on supportive care.

I don't feel however, that a H5N1-pandemic would be
well comparable with 1918.

"If and when it comes do we get triaged and morphine"

MRK, I would bet you my town has bought zero morphine,
(have no clue what the county or state has done),(SNS was for a handful of anthrax or smallpox or fallout, cases, right?) (I think they asked Santa for Tamiflu and pandemic vax, oh, and an extra vent per hospital. Ho ho ho.)
I did send the Palliative care (Scarce Resources) guidelines to my local owner-operated pharmacy, about "stockpile morphine" but, they never get back to me when I've sent them info before, though I take it the health dept or state had not said anything to them about preparedness.
The dying (and, their loved ones) would be lucky to get morphine to ease their deaths, from the looks of things so far...

By crfullmoon (not verified) on 23 Dec 2006 #permalink

Two years ago, it was 2-7 million mortality worldwide...only (World Health Organization - Dick Thompson). Now it is 20-60-80 million worldwide.

Next week who knows: more importantly who cares.

It is time to do a study on epidemiological studies. We should collect all the models and all the studies in respect to H5N1 and analyze them post event.

If they are as useless and inaccurate as I suspect, maybe the make work projects for unemployed epidemiologists will be over and they can do some useful forecasting like...where do we get the volumes of supportive therapies required to prevent unneeded deaths from secondary infections and conditions.

They can't control the variables, they could never control the variables...that's why you get results like alcohol is good for you etc.

Here's a good one...eating ice cream increases the likelyhood of dying from drowning.

Tom-The math on this sucks and 8% is what we were told to prepare for ....here. Money from the DHS budget is now being waylaid from protection to preparedness (not the HHS thing) and because of the demand the costs for th is stuff is up and off the scale. Its like I said they made a model a few months ago that shows the spread of H5N1. It was pretty as pictures go. It went from green to yellow to red to yellow and back to green. White on the map of the US was where people werent before. They deliberately omitted the end color white where people were gone. That is until I made a call or two.

I immediately popped off to my Senator and pointed it out and he put me in contact with some guys at Los Alamos and they gave me the "rest of the story" and an inside track on the models themselves. They have models now that based upon the initial cases and fatalities and all things being equal, show the white areas. Brother, there are some serious white areas that open up in and near population centers. They have it all the way up to a 50% mortality rate, estimated ineffectives, estimated living but expected to die from secondaries within a year, estimated effects against the economy, infrastructure, food supply and talk about ugly. Might be better to die.

I got to watch in real time as they ran it from a site they gave me temporary access to. 8% will be the tipping point, little more in rural communities, far less in cities. The end result is that I cant comprehend anything beyond 8% except to say deal with what you can, when and where you can. You vets are going to be the front line and likely see it before we do and if someone plays politics with it we are screwed and big. Vets are likely to become doctors in this.

CR-The states are laying in a lot of morphine and the National Stockpile should be enough I think. It could be a horrendous state of affairs when you have to in effect put your mom, wife, a child down. Cant think of people like dogs/cats or sick horses. This will change all of our perspectives just a month into it. Doctor do no harm, more like doctor do something to get my chest to quit hurting.

Happy Xmas thoughts.....

By M. Randolph Kruger (not verified) on 23 Dec 2006 #permalink

Morphine has the side effect of reducing 'air hunger', the perception that one is not getting enough oxygen/dumping enough CO2.

By Lisa the GP (not verified) on 23 Dec 2006 #permalink

You want a data set to prove either side of any argument?

No problem...as long as you pockets are deep enough.

Is epidemiology a regulated profession...end of story.

Revere. It must be a really good word; it's not in the dictionary.

Merry Christmas from the Great White(Green) North.

/:0)

The word may not be in your dictionary, Tom, but I recall it from my grad psych classes--damage to the frontal lobe of the brain can cause perseveration (on the Wisconsin Card Sort), a tendency to stick with a behavior past the time it is useful or appropriate [insert Bush joke here].

There is an interesting thread over at fluwikie which analyzes the speed at which the pandemic might spread. The most interesting part was the question of at what point would we become aware that the pandemic had actually begun. (For even those of us watching the situation like an obsesssive compulsive hawk) The answers ranged from 10 days into it, and onward (This is due to lag time between people being infected and becoming symptomatic, these symptomatic cases showing up at medical facilities, the facilities reporting/testing the outbreak, the test results coming back...we could be into it a month before we really heard enough to know it was happening.) The really scary thing, therefore, is that we simply cannot know early enough that it's begun, can't even rely on our own investigations and alertness to get the jump on this bug far enough ahead to SIP before we've been infected (especially if you are in proximity to the outbreak area). There is going to be alot of luck involved in this one. Preparing to SIP may give us at least some edge, but prayer (apologies to revere) is going to start appearing in more than one foxhole, I think.

By mary in hawaii (not verified) on 23 Dec 2006 #permalink

(hm...now, could that mean, it is past time for me to try and do anything about local, individual, community, relative's preparedness, and head for an island somewhere?)
(But, Wikipedia's definition doesn't read quite like yours STH, though it clicks very well with your joke example.)

MRK, glad to hear; "The states are laying in a lot of morphine and the National Stockpile should be enough I think."(how soon will it really get places- and do tptb ever plan to tell the public it is morphine?) "It could be a horrendous state of affairs when you have to in effect put your mom, wife, a child down."

-better that than have them suffer/suffocate from panflu for a day, or two, if people are given a chance to say their goodbyes first, though, I'm sure parents would rather be the ones to go themselves, if it somehow meant their children would survive.

Why not warn the public so they could try and prep and not get infected??

(What I don't really want to see, is people being "put down" because tptb anticipate "scarce community resources", and people because of some sort of criteria not making it through months of famine, ect, that might actually work something out. People that are dying; because of some sort of medical intervention that there are no more supplies/staff/grid for, well, I can see that, if they want it, and, if there's any morphine left. Fine line between hospice and homicide. Wouldn't want some nut doing away with all their political opponents, business rivals, wrong faith or ethnic group, ect. Though it would be very easy to do from a bunker, just by diverting resources away from areas, cordoning them off, whatever.

(Was that the Los Alamos map from April,2006? ..."Depending on the reproductive number R0, effective intervention strategies, including vaccination and targeted antiviral prophylaxis can be successful without resorting to economically damaging measures like school closure, quarantine and work or travel restrictions"?
School closures quarantine and travel restrictions won't cause much economic harm
if they protect people so they are alive after pandemic; to have an economy afterwards
-if we don't have vaxes that work, and don't keep people from spreading virus we might have a depopulating event.
Dead people have no economies. Depopulated regions have no government.
Where are our Continuity of the People preparations?

By crfullmoon (not verified) on 23 Dec 2006 #permalink

tom: perseverate - psychology: repeat a response after the cessation of the original stimulus; "The subjects in this study perseverated". STH's def. is OK, too. I have a joke that illustrates it but I'm too tired to write it all out and Mrs. R. wants me to vacuum.

Merry xmas to you to. A more formal and general wish to all goes up tomorrow morning in the Sermonette.

The authors give some reasons to justify this assumption. Latitude is a feature of geography, in particular seasonal variation and level of temperature which some think might be related to influenza outbreak patterns. This is feature that has not changed appreciably since 1918.

Tell that to migrating birds, pine beetles, butterflies, bears that aren't hibernating anymore, etc. Latitude is a proxy for climate. Climate today is somewhat different from climate in 1918. Winter begins later, and spring comes earlier, reducing the length of the indoor season, and the number of heating degree days.

Due to global warming, the seasonal behaviors of many animals and plants have changed significantly. Are the seasonal variations of flu be affected? I don't know, but some carriers of flu, humans and ducks, are affected.

I realize this nit doesn't affect your thesis, and it probably doesn't affect the conclusions of the paper, but 'seasonal variation and level of temperature' have changed appreciably throughout most of the northern hemisphere.

llewelly: I did consider climate change when I wrote that. My view was that the kind of variations that might affect influenza outbreaks are not the kinds that have been involved since 1918. But there are many unknowns. No one knows what drives flu seasonality, so it's hard to know if secular changes in climate are important from then to now or not, or if they are important at all.

As far as thats concerned MIH... I pray every goddamn day just like Patton did. yep folks I hope it doesnt come but you know on the 10th of December it was like someone flipped off the bird bug switch last year. Quiet as it could be. Then a little noise on the 27 and then confirmed deaths in Turkey.

I think the world is reporting this stuff but only calling it pneumonia to get it thru the holidays for all. We have the same parallels as last year, bird bug in birds showing up. Then normally some sort of human kill. We aint hearing about that. Whats a few people among friends when it will kill 81 million (maybe). I have seen the story line from all governments change like a chameleon with New Zealand being the most prepared country out there. They have less of a population than Tennessee but they bellied up as a nation and went right at it. Why havent we? Its the cost and the cost of effectively doing something about it. Because we have become a nation of expecting government to do all things for us we are in deep trouble. That government is the federal government and Katrina was a wake up call. That wake up call isnt that we should do more. I dont know what more could be feasibly done. The cost of doing what needs doing would take years and finish off the Medicare and Social Security systems that are already going to go dry.

Nope, I wonder if we might not have goat roped ourselves across all these years with false hopes and promises to the the people. Government and anything they can do will likely not be able to save anyone that isnt already slated by whatever fate to make it. 2 million yuan to save one Chinese kid. Thats a lot of yu's. We need a vaccine and they will produce something that will give limited protection for those of us who didnt get it in the first wave or two. Off specific vaccine...Shit. We are no better than vaccinating chickens and might mutate it yet again.

Of course it might not come.

By M. Randolph Kruger (not verified) on 23 Dec 2006 #permalink

MRK - How do you get such exclusive access to resources, such as Los Alamos models?

Patch-First you have to get a clearance. Doesnt take long for low level ones. I dont recall the exact level for this one but it wasnt bad. They operate on a need to know. You are a citizen and well, you need to know if you think you need to know. Then you press on to your local Senators office (works better going thru them) and they will get you the forms. Filling out paperwork bubba. Generally speaking as long as you are not a convicted felon or something weird in your background its not too terribly hard. Then you can get access.

Remind yourself that until its leaked into the press as all secrets are in this country and this one isnt a secret, its floating around everywhere now as I understand it that you have to be damned careful what you say. If they think you spilt something you'll get to be someones girlfriend in Atlanta Fed Pen. Generall prosecute you under the National Security Act, but there are plenty of other laws out there too.
E.g. if TWA 800 was knocked down by an accident or intentionally by a Standard missile as so many said, the people on the Navy ships that might have been responsible could be ordered not to make any statements of any kind. Sure they could be hauled before Congress to testify but in the same breath without grant of immunity (heard that one a lot in recent history) still be prosecuted under the act for saying anything to Congress or even another law enforcement agency.

You can also do it as an advisor to your Senator. Dont think for one minute that they dont want you to. Most of the positions in a Senators office are budgeted ones and someone has to pay for them. Yep its not just like whipping out the federal budget and writing ole so and so a check every month. They all have to be paid for it. In a lot of cases they are paid for by the funds collected during the election. The Senators pay the government so they can be under the Federal retirement system and the government pays the employee. I would go with the Senators though even though the same thing goes for the House. Those guys arent around long enough as a rule to be effective enough.

I will tell you though its a pain in the ass and they will go back and talk to your priest, old girlfriends, The cop who arresed you for .... and did you really eat your next door neighbors cat? They will question you about things you havent remembered for 40 years. Then you are subject to review every 2-5 years and you are supposed to report things that might change your status. That 2-5 year review is the way that these reporters find out so many things. As an advisor to your Senator in a "subject" area you will have to file reports, perceptions, and generally justify your level of clearance. Thats ambiguous though and if you do good your Senator might request your level be upped even more. The higher you fly though, you have to worry about how far you could drop too.

How high up? Again its based upon need to know stuff and that Senator will have a lot to do with that. Sometimes they will tell you stuff to see if you are leaking things. On the other hand, if he thinks you need to know then there isnt much you cant find out. Then once you do you find out you can only talk about it with people that have the same level clearance. Happens all the time in their offices, cant get the wheels to turn because the lower level workers cant be given enough information.

But, you could always wait three days and let the media spill it here as they are so wont to make news rather than reporting it. Drudge Report?

By M. Randolph Kruger (not verified) on 24 Dec 2006 #permalink

I'm a bit confused by the numbers generated in this study. Quoting: "In any event, the statistical model can then be used to predict excess mortality for a given population size with various age categories and per capita income as of 2004 (the latest year for which such data were available). In this way the authors toted up the excess deaths globally if a strain with the severity of 1918 were to emerge. The numbers are surprisingly high, with a median (50th percentile) of 62 million and a 10th to 90th percentile range of 51 million to 81 million."

My understanding is that the 1918 flu generated excess deaths on the order of those same numbers -- namely 60 to 80 million worldwide. So if the world population is so much greater now, and percentages today are similar to 1918, why arent' the total excess deaths higher for todays estimate?? Am I missing something or is my understanding faulty?? Thanks.

By Easy Hiker (not verified) on 26 Dec 2006 #permalink

Easy: This study uses only data from registration areas and estimates total excess mortality. Other estimates have used other sources (some not comparable with each other) and other methods. Previous estimates were quite varied and went from 20 million to 100 million or so for 1918. These methods estimate 60 million for now. These are all estimates. Read the paper and decide what you think. I see some difficulties with it and other experts I have talked to have concerns about it. This is not an easy problem, so we are talking about crude guesses, but they are based on actual data.

IMO a modern day pandemic will not model like the 1918 one did, not in the case of first world countries anyway.

Yes we have much better access to clean water, food, adequate housing and medical care than those in the third world. Now we do. If enough people get sick during the next pandemic, regardless of the mortality rate, essential parts of what it takes to make society work today will fail. In 1918 we were not dependant on electricity for heat and refrigeration, to pump water from wells. In 1918 we got most of our food from local producers or raised it ourselves because there was no refrigeration and quick transport of goods from far away. In 1918 the bulk of our population was not to be found in huge cities, but in rural areas where population density was much lower.

The world as we have it here is far different than in 1918. If we take away modern conveniences, even for a few weeks or months, many of us would not make it.

I've been flamed for it before, but I really believe that people in third world countries may actually fare better than us, in terms of weathering societal disruption.