The spate of swine flu articles in The New England Journal of Medicine last week included an important "Perspective, The Signature Features of Influenza Pandemics — Implications for Policy," by Miller, Viboud, Baliska and Simonsen. These authors are familiar to flu watchers as experienced flu epidemiologists and analysts of archival and other data. Analysis of archival data is sometimes described as archeo-epidemiologic research. In their NEJM article Miller et al. summarize what they see as some common features in the three flu pandemics of the last century (so the generalization that there are no generalizations about flu pandemics may have some exceptions; I won't pursue the paradoxes that result). The pertinence for the current swine flu outbreak is striking.
The authors suggest five signature features characgterizing pandemic versus seasonal influenza:
- emergence of a flu virus with which the general population has little previous experience
- peak mortality shifts to younger age groups than seasonal flu
- multiple waves
- enhanced transmissibility
- significant geographic variation
Swine flu has already satisfied the first. It is a novel virus to which most people are not believed to have acquired immunity, although the possibility remains that those of us born before 1957 may have some cross-reactivity. This relates to the second feature. The relative sparing of the older age groups and the increased mortality in younger adults may be related to "antigenic cycling," immune cross-reaction with a "new" virus by previous experience among the oldest in the population. The virus gains a foothold by rapid spread when most, but perhaps not all, of the population is immunologically naive. There are various hypotheses why young adults may be more at risk of dying, but at the moment we don't know the reason. It is pertinent that the age distribution of swine flu cases is markedly left-shifted (i.e., shifted to younger age groups). The age distribution also has obvious implications for how to use an initially scarce vaccine.
Of most interest for the present circumstance is the consistent appearance of successive waves of disease:
The third feature, a pattern of multiple waves, characterized all three 20th-century pandemics, each of which caused increased mortality for 2 to 5 years (see chart). The lethal wave in the autumn of 1918 was preceded by a first wave in the summer that led to substantial morbidity but relatively low mortality in both the United States and Europe. Recent studies suggest that these early mild outbreaks partially immunized the population, decreasing the mortality impact of the main pandemic wave in the fall of 1918. In the United States, the 1957 influenza A/H2 pandemic had three waves in the United States, with notable excess mortality in the nonsuccessive winter seasons of 1959 and 1962 — the latter being 5 years after the initial emergence of the pandemic strain. From 1968 through 1970, Eurasia had a mild first influenza season, with the full effects on morbidity and mortality occurring in the second season of pandemic-virus circulation. The reasons for multiple waves of varying impact are not precisely understood, but they probably include adaptation of the virus to its new host, demographic or geographic variation, seasonality, and the overall immunity of the population. The occurrence of multiple waves potentially provides time for health authorities to implement control strategies for successive waves. (Miller et al., NEJM [cites omitted])
Figure caption: Proportion of the total influenza-associated mortality burden in each wave for each of four previous pandemics is shown above the blue bars. Mortality waves indicate the timing of the deaths during each pandemic. The 1918 pandemic (Panel B) had a mild first wave during the summer, followed by two severe waves the following winter. The 1957 pandemic (Panel C) had three winter waves during the first 5 years. The 1968 pandemic (Panel D) had a mild first wave in Britain, followed by a severe second wave the following winter. The shaded columns indicate normal seasonal patterns of influenza.
Swine flu is currently experiencing a relatively less severe (first?) wave of disease. The virus could disappear or it could reappear as another wave or waves within a year or two (or three). Sometimes subsequent waves are more severe, sometimes not. It doesn't seem prudent, however, to think this one will disappear or remain a less virulent flu virus. Both are possible, but so are less benign scenarios. Plan for the worst, hope for the best remains good advice.
Enhanced transmissibility is, in my view, the least certain of Miller et al.'s features because its measure, the basic reproductive number R0, is difficult to estimate (R0 is the average number of secondary cases in a completely susceptible population). Miller et al. observe that the slim hope a flu pandemic can be contained is based on mathematical model that also suggests that to have any hope of containment, R0 would need to be below 2.0. Some data suggests that in a pandemic, R0 routinely exceeds 2.0.
The last feature, significant geographic variation, is also relevant to swine flu. Pandemic flu doesn't appear everywhere at once. Swine flu in Mexico is waning in some areas and increasing in others, and the same is happening in the rest of North America and Europe. The pandemic experience warns us not to characterize the state of a global outbreak on the basis of local or even national experiences. The swine flu outbreak is still evolving. As for whether it will wane with warmer weather, it is worth noting that in three of the four pandemics depicted in the chart, half or more of the mortality occurred outside "flu season" (the periods marked with the pink shading).
The NEJM swine flu articles appear to be free access. They are all worth reading.
I have a few questions which puzzle me w.r.t this historical information.
Firstly, do we know what causes a wave to peter out - is it seasonal factors, saturating the susceptible population.. or something else ?
Seondly, how does the current rate of increase in new cases compare with previous pandemicss
Thirdly, were people who caught the flu in previous first waves a) immune b) affected but less severely or c) just as likely to be affected by a later wave.
1) The News Media keeps suggesting that the current explosive exponential growth of swine flu will be halted by onset of summer.
2)But look at the growth of this flu in Arizona, where the temperatures have been around 100 degrees Fahrenheit:
May 7: 48
May 8: 131
May 10: 182
3) Similar growth has occurred in Southern California. So why do we think the spread of flu is going to slowdown in the northern USA as temperatures rise to the seventies?
silly question :: is flu season a function of temperature? How?
chris: We don't know why waves appear and disappear; se don't have data on previous outbreaks in the kind of time resolution we are looking at today; this is unique in that respect; first wavers were susceptible, that's why they got it. Presumably there was some cross reactivity with later waves.
Don: We don't understand seasonality. If you look at the charts in this post you will see that wexcept for 1968 almost half the mortality was outside of traditional flu season.
The lesson is clear: we can't predict what this thing will or won't do.
we maynot be able to predict what this new bug will do - but I bet you its unlikely politicians are going to take this oppurtunity to prepare for "the worst".
engstu: We don't know what makes flu "seasonal." It is not temperature, or at least not termperature alone. One of the big flu questions.
"Recent studies suggest that these early mild outbreaks partially immunized the population, decreasing the mortality impact of the main pandemic wave in the fall of 1918."
Glad thats settled.
I wonder how many pandemics we have had in the past that we are unaware of because they were so mild and escaped notice. Not saying this might not become nasty, but it seems just as likely it could get milder. Just have to watch I guess. If nothing else it is a good opportunity to study how new flu viruses progress.
Amazing to me that science still has so many questions about something as common and widespread as influenza which kills 36,000 people per year (12-9/11's per year) in the US alone. I sometimes wonder how much of science is not in the public domain due to security or other reasons, given that much of the funding for research comes from government.
Some folks believe WW I was won due to the impact of the flu on German troops as they were making decisive gains on the battle field, so influenza should certainly be heavily researched for military reasons, yet the big questions outstanding suggest not.
Sorry if this is somewhat off-topic, but do you think the government should recommend that people get the pneumovax vaccine to protect against bacterial pneumonia?
Jon: Yes, I do. Get a pneumovax. You only need to do it once. It doesn't protect against all secondary infections, but it does protect against one of the main ones.
Re revere at 6: "We don't know what makes flu "seasonal." It is not temperature, or at least not termperature alone. One of the big flu questions."
1) And here I thought --based on a recent NIH research report via Reuters --that flu viruses covered themselves with a "buttery like substance" (one of those aromatic sun tan lotions/body massage oils?) and that they expired in the summer because their Tahiti Sweetie melted and evaporated:
Which --last time I checked --don't do very well at 100 deg F.
Playing devil's advocate here, if indeed this 1st wave is milder and getting this version would provide protection against a possibly more deadly 2nd wave, doesn't that argue in favor of swine flu parties now? Note here that I think they are a bad idea, but I can see the logic. It follows somewhat the logic that says give everyone a course of tamiflu to keep at home and use at the first sign of disease. The folks who get infected and "cured" by early application of antivirals will then be immune and able to care for those who become ill when the antivirals run out (or become useless due to resistance.)
sounds good to me (:
MoM: No, I think the arguments I gave earlier stand unchanged.
the buttery lipid coat melting in 100 degree weather before it can get into a respiratory tract & ordering in colder temperatures. Not the tamiflu dosing of swineflu partys - sorry.
I was under the impression that warmer months lead to increased UV, and it was the UV that killed the flu virus.
Isn't absolute humidity a key factor in flu virus survival?
Jon-My personal experience with pneumovax has been very good. Not sick all winter... not even a crappy nose. I got it three years ago but not the flu shot(s) along the way. Here is the Merck PDF on it.
Down south during the winter and the wet its just the right temp for just about everything. Not cold enough to kill it, nor warm enough. Flu season is a bitch in a good year. Since its wet outside every one comes inside and spreads what ever is going around. Sure cant hurt to get the pneumo... BUT, I will tell you that you can save some bucks by getting your shot nurse to toss it into the bag when she comes to give flu shots, about 30 when she does it. About 80 in the docs office... One other thing.... Do it on a Friday because your arm is going to swell a bit, numb up, and you likely will run a fever from it. Most Walgreens have it available year round.
re: seasonality. Doesn't that people stay in close quarters with limited ventilation contribute? More people stay inside, do not allow (outside) air exchange, and suffer overall lower indoor humidity means the "bad" air stays inside and it sticks to indoor surfaces quicker. The example of Arizona might be a harbinger - people gather indoors to escape the heat and create similar conditions.
re: 1918 pandemic. How did overall health contribute? Wars interrupt food supplies, raise stress levels, and make everyone's life miserable, even if they are not on the front or in the Army. It also gathers together large groups (soldiers) then disperses that group to various corners of the world. The combination of rationed food, emotional agitation, and overall hardship must have been something of a factor.
I think that there is a good possibility that we may see a change in the wave behavoir of past pandemics. This may not occur in the northern hemisphere with Mexican Flu due to its beginning here in the spring but OTOH as pointed out by Revere above pandemic flu does not obey seasonality the same way the regular flu does.
Below is an excerpt from The Coming Pandemic Catastrophe which discusses the factors present today that may result in there being a single massive worldwide wave that affects the planet everywhere at the same time rather than multiple smaller ones.
Grattan Woodson, MD
The likely change in pandemic wave form
The three twentieth-century pandemics occurred in discrete waves. While the entire event lasted for a few years, the action was compressed into two or three periods of a month or two each. In the United States, the 1918 Spanish Fluâs first wave was more severe than the usual seasonal flu but not all that bad. It was the second wave that re-emerged in September 1918 with a vengeance that caused ninety percent of the U.S. deaths during the pandemic. The third wave beginning the following winter in the United States resembled the first wave in severity. Over the following couple of years, there were multiple regional mini-waves worldwide that continued to harvest higher than usual numbers of people due to flu and its consequences. It is of note that these waves peaked in different world regions at different times and without regard to season of the year.
The reason for the wave phenomenon is not known but was probably in part related to the speed with which humans traveled, population density, the general health of the population affected, and the intervention of the heat of summer, which in past pandemics has been observed to temporarily interrupt but not universally the spread of the virus within the human population.
Modern intercontinental travel via jet aircraft by millions of persons each day will dramatically change the speed with which the next influenza pandemic moves through the worldâs population. This factor, together with the highly concentrated human population within urban areas and the inherent vulnerability of our increased numbers of elderly and infirm citizens, create the conditions for a massive single tsunami-like pandemic flood that inundates the world virtually simultaneously for a prolonged continuous period.
An event like this might last from six to nine months depending upon what time of year it began and carry with it much higher transmission rates than seen previously. The advent of summer might temporarily halt the pandemic that will probably resume once more with the return of cooler weather. There would likely be subsequent wavelets of much less intensity for a year or two afterward as the pandemic virus picks off those who escaped its initial grand attack.
This scenario would result in a much higher clinical attack rate of influenza than would be the case if the pandemic occurred in short defined waves interspersed by disease-free periods as in the past. The speed of viral transmission between people will be fueled by these same factors, resulting in a significantly higher rate than projected by health authorities. The deluge of critically ill influenza patients will rapidly overwhelm all health care systems. This will result in a higher case fatality rate from the virus and crude all-cause death rate during the pandemic period than expected due to people with serious but treatable influenza complications and people critically ill with a host of common non-influenza conditions being denied access to conventional hospital care.
Also worrisome is the effect a single prolonged wave of this magnitude would have on the fragile global economy. It would be crushed by an event of this intensity. The civil unrest stemming from this occurrence would be sustained and profound. While it is impossible to predict the impact of civil disorder in prospect, during the period of anarchy that would follow, great loss of life and property is inevitable. Uncontrolled growth of the human population and its concentration in cities since 1918 are the primary factors that place us at exceedingly high risk today from a severe influenza pandemic.
Revere, how about for swine? I read that swine used to have seasonal flu viruses but now have viruses all the time. Do swine or any other animal get epidemics (locally instead of worldwide) that come in waves?
Certainly poultry and some birds? in Indonesia have been in a constant epidemic of H5N1 for some time. Are there waves associated with those epidemics?
Regarding seasonality, there have been numerous "solutions" (including the recent guinea pig experiments from the Palese lab purporting to show that humidity is the key variable. As we have observed, none of the explanations is in complete accord with what we see. The recent paper on seasonality in Nicaragua (a tropical climate) is an example. Also note that regarding waves during pandemics, the number and relative severity of waves differs in the last four pandemics and that half the cases for 3 of 4 occur outside of regular flu season.
So we still don't understand the dynamics of this disease. I am sorry to have to repeat this so many times, but it isn't the things we don't know that are most dangerous but the things we think we know that we are wrong about.
Regarding swine, there hasn't been systematic surveillance of animals anywhere, including the US. This is an important question. Bird flu also seems to have a seasonality. Whether this is true of swine, too, we aren't sure.
Considering the geographic variation in the epidemiology of influenza, this virus seems to have spread across the planet at breakneck speed. Considering the interconnectedness and rapid mobility of globalized societies it's hard to image a virus could ask for a more ideal system for transmission. It seems like a pathogen with a high Ro that was less susceptible to geographic variation, and had a long enough incubation period to escape detection for a week or so could be unstoppable.
ravyn: It's not just the Ro but the fairly short serial interval that makes spread fast. But in general, you are right. A transmissible virus like this is not containable and any wishes to the contrary are futile.
Re revere's comment: "A transmissible virus like this is not containable and any wishes to the contrary are futile."
So what happens when there are 100 million or so cases in Southeast Asia and it starts mixing with the Avian Flu virus within the same victims?
On the other hand, maybe we won't have to pay off that $Trillion or so in Treasury Bonds that China and Japan are holding.
Don; What happens? I don't know. If you know, tell me.
Re revere's comment "Don; What happens? I don't know. If you know, tell me. "
1) I don't know either--that's why I'm asking. But , as I noted in an earlier thread, some experts have expressed concern over the swine flu mixing with the avian flu in the same victims.
2) Given that the USA has replaced Mexico as the major incubator of this new virus, why isn't the US government taking similar strong measures to subdue the virus's spread? Why aren't we having a week long national curfew so that the households with flu victims can be identified and isolated?
3) Is it because of the economic cost -- because our major banks are on ventilators in the Intensive Care Unit?
4)Doesn't allowing the continued spread amount to sacrificing a lot of High Risk victims --both here and abroad? And even if one is indifferent to that, isn't there a risk that if we allow this virus to spread beyond our shores it will come back to us in a far worse form?
5) I'm not qualified to debate that policy issue on national TV --but what's interesting is that the news isn't even pointing out that that issue exists and that a decision is being made.
Don: There are numerous trade-offs here. Many of the severe methods you suggest are likely to have unintended consequences that would be worse than the consequences. Suppose this is like the pandemic of 1957. Many people alive at the time don't even remember it and weren't affected. It is not an easy call, and so far it would be like doing this for a normal flu season. That might or might not turn out to be the case but the cost would be extremely high, not just in money but in lives.
As some one pointed out here our medical system is totally incapable of handling a big outbreak of influenza. Especially now that our health care system has spent the last 6 months downsizing, that was in response to the economic downturn. There is a greatly reduced hospital capacity from just the end of the 20th century when we had a pretty big flu out break. I can remember very well that hospitals were overwhelmed during the flu outbreak of 2000 and that was before the recent downsizing. For the first time in about 15 years nurses are being laid off and new graduate nurses can't get jobs. If I were a person with any clout I would insist that all health care institutions begin hiring excess nurses above what they need at present and get them oriented over the summer. That way when winter comes and the H1N1 comes back from it's summer break there will be enough nurses to care for everyone. Woe to anyone who gets sick enough to require hospitalization during a flu outbreak over the next few years. There will be no room at the inn. Deaths from heart attacks, car accidents and other sorts of illnesses may well increase because the system will be so clogged by flu victims. PS it might not be a bad idea to buy more equipment, however they way things sit right now there will be no one around that even knows how to operate the equipment because hospitals have downsized there nursing work forces.
Thank god I have this wonderful invention called a immunesystem. Nature invented it so that I don't need to be scared by the stories you tell or make up. This wonderful system evolved in a holistic manner, taking in account many, many, many more factors then all combined virologists on earth could in a 1000 years. And most important of all, it did so without any industrial, corporate of shareholder bias. So, you won't see me taking Tamiflu or anything else.
Besides, I didn't see any publication yet that proves the reliability of the serological tests that are used. From HIV it is known that there exist many, many factors that will produce a false positive on a WB of ELISA. Come to mention it, I didn't see any publication yet that proves the H1N1-markers to be unique for any infectious desease.
As for the seasonal thing in flu.
Revere -- could you please revisit the whole notion of waves? It seems timely given that infection rates remain high (Great Britain as an example) and at the same time, things are also crazy in Argentina and Australia. Here we are, almost mid-July - by my count, H1N1 has been steadily on the march for going on four months now.
As all the authorities keep referencing how we need to prepare for a "fall' resurgence, the way this thing is behaving begs the question of when this first wave can be considered technically 'over' - it might not happen until mid-August or later. Doesn't leave room for much of a reprieve and definitely not enough time for businesses & communities to prepare.
I am starting to wonder if the author of The Coming Pandemic Catastrophe got it right.. that our modern world has created the perfect petri dish for a massive single tsunami-like flood.
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