Tag Archives: A(H1N1)

Measuring Epidemiological Contacts in Schools

I am happy to report that our paper describing the measurement of casual contacts within an American high school is finally out in the early edition of PNAS. Stanford’s great social science reporter, Adam Gorlick, has written a very nice overview of our paper for the Stanford Report (also here in the LA Times and here on Medical News Today). The lead author, and general force of nature behind this paper, is Marcel Salathé, who until recently was a post-doc here at Stanford in Marc Feldman‘s lab.  This summer, Marcel moved to the Center for Infectious Disease Dynamics at Penn State, a truly remarkable place and now all the better for having Marcel.  From the Penn State end, there is a nice video describing our results as well as well as a brief note on Marcel’s blog.  This paper has not been picked up quite like our paper on plague dynamics this summer, probably because measuring casual contacts in an American high school generally does not involve carnivorous mice.

With generous NSF funding, we were able to buy a lot of wireless sensor motes — enough to outfit every student, teacher, and staff member at a largish American high school so that we could record all of their close contacts in a single, typical day. By “close contact,” we mean any more-or-less face-to-face interaction within a radius of three meters.  As Marcel was putting together this project, we were (once again) exceptionally lucky to find ourselves at Stanford along with one of the world authorities on wireless sensor technology, Phil Levis, of Stanford’s Computer Science department.  Phil and his students, Maria and Jung Woo Lee, made this work come together in ways that I can’t even begin to fathom.  This actually leads me to a brief diversion to reflect on the nature of collaboration.  As with our plague paper or SIV mortality paper, this paper is one where collaboration between very different types of researchers (viz., Biologists, Computer Scientists, Anthropologists) is absolutely fundamental to the success of the work.  In coming up for tenure — and generally living in an anthropology department — the question of what I might call the partible paternity of papers (PPP) comes up fairly regularly. “I see you have a paper with five co-authors; I guess that means you contributed 17% to this paper, no?”  Well, no, actually.  I call this the “additive fallacy of collaboration.” When a paper is truly collaborative, then the contributions of the paper are not mutually exclusive from each other and so do not simply sum.  To use a familiar phrase, the whole is greater than the sum of the parts.  Our current paper is an example of such a truly collaborative project.  Without the contributions of all the collaborators, it’s not that the paper would be 17% less complete; it probably wouldn’t exist. I can’t speak particularly fluently to what Phil, Maria, and Jung Woo did other than by saying, “wow” (thus our collaboration), but I can say that we couldn’t have done it without them.

I’ll talk more about our actual results later.  For now, you’ll either have to read the paper (which is open access), watch the video, or read the overview in the Stanford Report.

Latest Swine Flu Epidemic Curve for the United States

It’s been a while since I last posted about swine flu.  Alas, it is still with us. The most recent data from CDC show that swine flu is still with us and that we should steel ourselves for a heckuva flu season this autumn and winter.  The curve peaks around the middle of June, but this is well past a typical flu season.  The influenza virus apparently does not survive well when the absolute humidity rises as temperatures rise and the air can hold more moisture.  When the weather gets cold again in the northern hemisphere and the absolute humidity drops, the virus will better survive outside of its infected host and transmission will increase.

Here is the epidemic curve as it currently stands:

CDC reported confirmed influenza cases for 2008-2009
CDC reported confirmed influenza cases for 2008-2009

It reassuringly appears to be tailing off, but in reality, it is just experiencing a summer lull (remember, also, that there is quite a bit of under-reporting at this point).  It should start to pick up in October or so when the bars representing the incident cases will almost certainly dwarf the current ones.  We’re working on a number of flu-related projects, including the very precise measurement of within-school contact networks (recently funded by NSF!) as well as a project on perceptions of vaccination and (we hope) the measurement of vaccine opinion clustering.  My collaborator on this project, Marcel Salathé, has a terrific paper with Sebastian Bonhoeffer at ETH on the impact of opinion clustering on infectious disease eradication through vaccination. Their work shows that the standard estimates of necessary vaccination coverage required to protect the population through herd immunity are overly optimistic if people who share anti-vaccination beliefs, and therefore do not vaccinate themselves or their families, cluster in a population.  I will try to update, but I fear it will prove to be a very busy Autumn for me…

Under-Reporting of Swine Flu

A very interesting epidemiological analysis of the first cases of novel A(H1N1) flu in China was posted on ProMED-mail this morning by Dr. Ji-Ming Chen, Head of the Laboratory of Animal Epidemiological Surveillance, China Animal Health and Epidemiology Center, Qingdao. Dr. Chen notes that all 12 of the cases in China were imported via air travel.  He writes, “if the prevalence of the A (H1N1) infection among the international airplane passengers is comparable to that in the departure countries, there should be many more cases in USA and Canada than the official records (more than millions?).”

How can this be?  There is more evidence in Chen’s epidemiological analysis.  Of the twelve imported cases, only two were identified as possible cases using airport temperature scanners.  These two individuals were the only patients to complain of discomfort (i.e., flu-like symptoms) on their flights.  It seems quite likely that this particular strain of influenza produces very mild, sub-clinical symptoms in many of its victims.  The implication of this inference is that infection could become very widespread without being noticed by public health officials or the public at-large.

Daily Flu Counts

The bad news is that cases of novel 2009 influenza A(H1N1) continue to increase. Data from WHO Epidemic and Pandemic Alert and Response (EPR), Influenza A(H1N1) – update 43 — 23 May 2009:

The good news is that the spread appears to be sub-exponential at this point.  Exponential growth will appear linear on semi-logarithmic axes.  Here I plot the natural logarithms of these same case-count data against the date. We can see a distinct (negative) concavity, indicating that the growth in confirmed cases is sub-exponential.  The usual caveats about under-reporting and the lag between infection and reporting dates apply, but this is a modicum of good news.

The austral flu season will be heating up (as it were) soon enough. Once again, it seems only prudent to me that the richer nations of the north help poorer nations, who are about to get hit, with efforts to contain the spread of novel A(H1N1).  Given the relative genetic homogeneity of this novel strain, choice of a strain to include in a vaccine is straightforward (if a little late for the beginning of the northern flu season).  If we can minimize the intensity of antigenic drift (despite the name which might imply random change, this is directional selection away the ancestral antigenic type in the presence of multiple circulating strains) by minimizing the number of cases in the south during their flu season, perhaps we can dodge the bullet of an extremely high-mortality pandemic.

More On Flu

There is a nice video piece at the New York Times website done by science reporter Donald G. McNeil Jr.  In it, he makes a number of important points that I have been trying to emphasize in my latest posts on the topic. McNeil is to be congratulated.  This is the kind of reporting we need now and in the coming months on swine flu.

The New Scientist also has an editorial (which I just found because I’m behind on my RSS reader) which notes the distinct possibility that H1N1 could come back with a vengeance this Fall.  Note that most of the deaths in the pandemic of 1918 occurred in September of 1918 even though the first cases were reported in March of 1918.  The pandemic of 1918 (which was really the pandemic of 1918-1920) killed 50 million people, perhaps as many as 100 million.  The world population in 1920 was 1.86 billion, which means there were around 1.78 billion or so in 1918.  The case fatality ratio for the 1918 flu was >2.5%, and perhaps as high as 5%, which means that 25-50 people died out of 1000 infected with the flu.  All in all, this means that anywhere from 0.5% to 2% of the world’s population died during the pandemic of 1918 (though if 100,000,000 people really died, then the overall world mortality rate was actually over 5%!).  The following figure (from Taubenberger and Morens 2006) shows the time series of deaths from flu for 1918-1919.  

Taubenberger and Morens (2006), Figure 1.

The most striking feature of this figure is the pronounced spike in mortality in the Fall of 1918.  We are currently a month before this time series starts in our current potential pandemic. Note that the death rate in June of 1918 was not too dissimilar from the mortality rate estimated from Mexican outbreak data by Fraser et al. (2009).

The New Scientist also reports that a flu vaccine incorporating the new A(H1N1) is unlikely to be available by the Fall of next year.  This is, of course, distressing news.  So, what can we do?

It seems to me that the best plan is to follow D.G. Margaret Chan‘s call for international solidarity.  She has rightly noted that the people likely to be hardest hit by the an H1N1 pandemic (or any other infectious disease for that matter) are the citizens of the world’s poor countries.  They are the ones who bear 85% of the infectious disease burden, after all.  So, why should we in the developed north care about this other half (homage to Yogi Berra intended)?

For the time-being the strain of A(H1N1) is relatively benign (just as it was in 1918 at this point), but influenza has an incredible capacity to mutate, recombine with other co-circulating flu strains, and respond to selection (the part that you don’t typically hear about in news reports). Let us not forget that there is currently another highly pathogenic strain of flu out there. Highly pathogenic Influenza A(H5N1) — remember bird flu? — has an overall mortality rate of approximately 60%. Yes, that’s an order of magnitude greater than the high-ball estimate for the 1918 flu.  Of course, this variant of influenza has only infected a total of 424 people in the world since 2003.  141 of those have been in Indonesia (where 115 have died for a case fataility ratio of 81.5%).  We have gotten very lucky so far with H5N1 because it is not efficiently transmitted from person-to-person.  The emergent H1N1, however, is.  It’s basic reproduction ratio is substantially greater than that of seasonal flu, which indicates it is very efficiently transmitted. God help us if a recombinant strain with the pathogenicity of bird flu and the transmissibility of swine flu were to evolve.

This suggests to me that a little bit of financial and technical assistance from the north to the countries of the south might be a very good investment at this point. Let’s help developing countries entering their flu season control swine flu to the absolute best degree we can manage. Minimizing the number of cases also minimizes the evolutionary potential of the virus — fewer infections, fewer opportunities for mutation and subsequent selection. I realize that we are in the throes of a major economic crisis, the likes of which we haven’t seen since 1929.  But, do you have any idea what losing 5% of the world’s population would do to the economy?

Keep Washing Your Hands

As the potential pandemic fades into the obscurity of a couple weeks’ worth of the 24-hour news cycle, cases continue to mount.  New York City reported its first swine-flu death, an assistant principal in a NYC public school. As with most of the other deaths so far, this particular victim had medical complications that contributed to his especially severe illness.  This is typical for influenza and other serious respiratory illnesses like SARS.  One of the greatest risk factors for dying of SARS during the outbreak of 2003 was being a diabetic (Chan et al. 2003).   Flu is dangerous.  As noted by Thomas R. Frieden, New York City’s health commissioner and Obama appointee to head CDC, “We should not forget that the flu that comes every year kills about 1,000 New Yorkers.”  As I noted in a previous post, analysis of the outbreak data from Mexico suggests that the current influenza A(H1N1) has a case fatality ratio a little bit higher than the usual seasonal flu, so we should expect it to kill more people, though not dramatically more.

The number of cases continues to rise in Japan, another northern hemisphere country with high-functioning public health infrastructure, despite how late in the season it is. The Japanese government has closed over a thousand schools around the western cities of Kobe and Osaka in an attempt to curtail transmission.  So far, there does not appear to be sustained community transmission, but again, it is remarkable that there is any  transmission to speak of this late in the flu season.  One other troubling part of this particular outbreak is that the school cluster around Kobe and Osaka is not associated with overseas travel as clusters in the United States and Europe have been.

WHO Director General Margaret Chan announced at the recent meeting of the World Health Assembly that the apparent quiescence of flu activity now — even as WHO has kept its pandemic alert at level 5 — could still be “just the calm before the storm.”  She urged countries to work together to continue to control the current outbreak of A(H1N1), noting that those most vulnerable remain the poorest of the world’s citizens. As quoted in the NY TImes, “I strongly urge the international community to use this grace period wisely. I strongly urge you to look closely at anything and everything we can do, collectively, to protect developing countries from, once again, bearing the brunt of a global contagion.”

Just to highlight the fact that, despite the media silence, the swine flu outbreak continues to grow globally, I will post an updated plot of the WHO case counts for today.

Yes, cases continue to rise.  Let’s continue to take reasonable personal precautions, help with the battle against flu in countries of the southern hemisphere, and prepare for the next flu season here.  It never hurt anyone to wash their hands a couple more times a day.

Pssst, Swine Flu is Still Here

The coming Aporkalypse appears to have faded into last week’s obscurity. With WHO raising the pandemic alert from 3 to 5 in the span of about 24 hours, it seemed that Oinkmageddon was upon us.  But now it’s hard to find a news piece on swine flu, let alone an inflammatory one. This is something that worries me and lots of other public health professionals. Not so much the lack of inflammatory new pieces. More, I worry that people are going to see this incident of just another case of health officials needlessly pushing the panic button.  There is always the possibility that the public health measures enacted to control extensive spread of Influenza A(H1N1) may have actually worked! The epidemic fizzling when the alert goes to level 5 is really the best possible case, right? Alas, I doubt that it’s really the case.  As I noted before, it seems unlikely that we will have extensive sustained transmission in the northern hemisphere at this late date. But case counts continue to grow globally and the austral flu season starts in the not-too-distant future.  

WHO publishes case counts each day, and I have plotted them from 30 April through 13 May.  These are the worldwide confirmed cases as of this morning.

WHO worldwide confirmed A(H1N1) cases as of 14 May 2009We can see that the case count does, in fact, increase each day and shows no sign of slowing down. This is true, incidentally, whether one plots the cumulative number of the incident number — clearly this plot is more dramatic, but the incidence does not show any obvious sign of decline. Of course, there is an inherent lag in the reporting of confirmed cases, so it is at least possible that the number of cases has peaked.  But I doubt it.  Recent analysis by an international team of epidemiologists suggests that the reproduction number (the average number of secondary cases produced by a single primary case in a completely susceptible population) is substantially greater than that of seasonal flu.  The reproduction number tells us how fast and how far an infectious disease will spread and how many people will ultimately be infected and higher values of the reproduction number mean faster, further and more. This team also found that the estimated case fatality ratio is less than that of the 1918 pandemic strain but comparable to the 1957 pandemic strain.  So, given proper environmental conditions for transmission, this variant of the flu looks like it could spread rapidly, widely, and cause a decent amount of mortality.  It seems entirely possible that this is exactly what will happen in the southern hemisphere in the coming months, after which it will come back and hit here in the north.

As I noted before, I can hope is that people have not become inured to warnings of epidemics because of our recent experience with H5N1 bird flu and this new H1N1 swine flu (there is also the last swine flu scare of 1976).  Some saner press coverage would help. Of course, it would mean less grist for the mills of John Stewart and Stephen Colbert, but it might mean a public better prepared for a potentially real public health emergency that we still may face.

On Swine Flu

A lot has happened in the last week.  I was frantically preparing for a big talk that I had to give at the end of the week when the news about swine flu started heating up.  As of the most recent posting from the Pan-American Health Organization, there are 1118 confirmed cases and 27 deaths in 18 countries worldwide. The United States has had 279 laboratory-confirmed cases and one death.  As I write, it sounds like the epidemiological situation is much better than it could have been.

But last Monday things were looking like they were going to get very serious. While I should have been preparing for my talk, I spent the day working out the details for an internet-based survey on people’s knowledge, attitudes, and behavior regarding the emerging H1N1 (a.k.a. “swine”) flu. Marcel Salathé and I realized that we had an historic opportunity to field a survey and learn something about people’s responses as the public health emergency unfolded.  Our survey has been online since the morning of Wednesday, April 29th (and is available here for anyone interested in taking it — it’s only 16 questions long and takes less than five minutes to complete) and we have gotten well over 5,000 responses so far. Vijoy Abraham at the Institute for Research in the Social Sciences was amazingly helpful in helping us get the survey online in a hurry, and IRiSS very kindly hosted the survey.

Marcel posted a nice blog piece on the survey and it was later picked up by Carl Zimmer on his blog, and then the big-time: we got written about on boing boing.  This idea clearly resonates with people.  Stanford put out a press release and now Marcel and I have done a number of interviews for various local and international media outlets (links forthcoming).  All this before we’ve even done any analysis!

We will keep the survey online as long as it is relevant, though we will begin doing some exploratory data analysis shortly. The thing about flu is that, even though it seems like it is fizzling out already, it could actually kick around for months. I was speaking with a prominent disease ecologist this past week who predicted that this particular outbreak would fizzle in the northern hemisphere for the time-being. You see, by May, we are pretty well past flu season in the north.  For whatever reason, flu shows marked seasonality in transmission.  Jeff Shaman at Oregon State has shown pretty convincingly that this seasonality is a matter of absolute humidity, which is lowest in the winter in temperate regions and is presumably more conducive for influenza transmission and virus survival. The disease ecologist who made the prediction for northern-hemisphere fizzle also suggested that the southern hemisphere might be in for a hard flu season during the austral winter.  Extensive and sustained transmission could be bad news for those of us who feel like we’ve dodged a bullet here in the north because when flu season rolls back around here, we might get slammed on the rebound.  A very interesting paper by Cécile Viboud and colleagues shows that it was the second influenza season that had the higher mortality rates during the last influenza pandemic of 1968.  The moderator on ProMED-mail wrote “Even if the present A/H1N1 has pandemic potential it is therefore highly likely that the outbreak will fade out within the next 2 to 3 weeks, but it will reappear in the autumn.”  Time to get cracking on getting this H1N1 strain incorporated into the next flu vaccine, I’d say.

This means that we will probably need to keep our survey up for a while to come.  It will be interesting — and hopefully informative — to see how people’s anxieties and knowledge about swine flu wax and wane as this system evolves. 

That’s all for now though I suspect this won’t be the last post I write about swine flu. Oh, and the talk turned out fine; thanks for asking…