Among the crucial questions that seems to have prevented the WHO so far to declare the emergence of the “swine flu” virus in Mexico and the US a pandemic appears to be the question of severity. So far, the cases in the US (in contrast to those in Mexico) have been very mild. Since the classification of the event as a pandemic would automatically lead to much more extensive interventions, the WHO understandably wants to be cautious at the moment. However, this points to an interesting and important question. In what sense does the fact that pandemic preparedness has largely been focused on “avian influenza” and the assumption either implicit or explicit of a severe pandemic both enable and disable certain kinds of interventions today. I think this might be an interesting question to follow in the next few weeks.
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Two things related to this question puzzle me. First, cases in the US would be substantially less remarkable without incidents, and a presently significant case fatality rate in Mexico, with which to contrast them. 20 cases after 3-4 days of intensive active surveillance versus over a thousand…? (I am curious how these cases have been tracked and documented, but that’s another question…) Which brings me to my second point. Relatively few cases so far in the US and globally, with few publicly available signals to indicate a substantially higher attack rate is here or on the horizon. It’s all speculation right now, but I’m wondering where the ‘bang’ is…
All of this is, of course, what Carlo is transforming into a problem – which is great. Yet if this does fizzle, or remain relatively rare, I do question whether and how a transformation of the pandemic category will occur. My sense is it will validate public health authorities’ cautious approach in labeling this event.
Of course, this could all change tomorrow…!
Yes, I agree. But the key issue here is the transmission. Cases in California, Texas, Kansas, New York… etc. and in a relatively short period of time. The links between most of these cases is completely unknown. This points to a rapid spread with a significant number of undetected cases of infection. Also, as officials are already acknowledging, they don’t believe that they can really contain the spread of the virus.
From the perspective of transmission, this certainly seems to be a pandemic and I think that the event will be labelled as such tomorrow by the WHO. We will see what happens …
… as to surveillance, there is an interesting post from promed.:
“In an earlier posting, this moderator pointed out that the reported cases
in Mexico were hospitalized pneumonia cases, with surveillance data coming
from inpatient facilities. In contrast, the information on the reported
cases in the USA involved surveillance data coming from outpatient
facilities. This difference in sentinel reporting sites biases reported
cases in Mexico to be more severe cases as they are cases that were severe
enough to merit hospitalization. In turn, the use of outpatient sentinel
surveillance sites in the USA leads to a bias selecting milder cases —
those that do not require hospitalization. One suspects that once the
countries heighten ILI surveillance to include both inpatient as well as
outpatient facilities, these disparities will lessen. One also suspects
that the true number of cases in Mexico is significantly higher than the
currently reported approximately 1500 cases, which would further lower the
calculated case fatality rate (CFR). (Information on the actual number of
reported cases in Mexico is not readily available on the Ministry of Health
website, so all figures are estimates based on earlier figures provided in
CDC and WHO reports and on newswire reports. Hopefully these figures will
be available on a regularly updated basis to permit following the course of
the outbreak).”
Carlo, Dale and other ARCers,
Please keep this discussion going.
What is the right analogy? There are comparisions to SARS, Avian Flu, and the Fort Dix event.
Perhaps we should keep track of these analogies and others.
Also what triggers the next higher level of surveillance and quarantine.
Finally– an event! Or is it an episode???
I am sorry, but I think this is almost certainly an event. What we are seeing now is fundamentally different from and much more serious than both the avian influenza situation and the 1976 Fort Dix incident.
What is unique is that we have a pathological event (most probably a pandemic) caused by a subtype of the influenza virus, which is already circulating. So in that sense, there are no comparable cases in the 20th century, except perhaps the “re-emergence” of H1N1 in 1977 (but that was due to an accident in a field trial with vaccines in China).
I think because the current event doesn’t really correspond both to recent predictions and current doctrine, the experts are struggling to figure out what would trigger the next higher level of intervention.
We are seeing some of the SARS dynamic play out in questions of travel restrictions. Hong Kong – which bore the economic brunt of the travel cut off in 2003, is now being the most reactive. The EU just advised Europeans not to travel to the US. Whereas the US is following the assumption that containment will not work. Rather, preparedness and thus Janet Napolitano says we are declaring, not “emergency” but “emergency preparedness.”
There are a number of explanations for the observed differential in the severity of cases between Mexico and the rest of the world that are unrelated to ongoing mutation of the virus or wistful speculation that the flu is going to be more mild outside of Mexico. As Carlo pointed out, from ProMED, the first cases in Mexico were reported from inpatient facilities, whereas the first U.S. cases were reported from outpatient. The more mild cases in Mexico likely not flagged for typing. From one of the NY Times’ articles
http://www.nytimes.com/2009/04/27/world/27flu.html
“The central question is how many mild cases Mexico has had, Dr. Martin S. Cetron, director of global migration and quarantine for the Centers for Disease Control, said in an interview.
‘We may just be looking at the tip of the iceberg, which would give you a skewed initial estimate of the case fatality rate,’ he said, meaning that there might have been tens of thousands of mild infections around the 1,300 cases of serious disease and 80 or more deaths. If that is true, as the flu spreads, it would not be surprising if most cases were mild.
Even in 1918, according to the C.D.C., the virus infected at least 500 million of the world’s 1.5 billion people to kill 50 million.”
The CDC, by the way, has created a swine flu page http://www.cdc.gov/swineflu/
Carlo — I want to push you one more time: it is an “event” but the question is — what precisely is in motion, in play, at stake, in a process of reformation, etc. It seems like what you are insisting on in terms of novelty concerns a specific issue about the technical definition of a pandemic. But it would be helpful (particularly for me since I don’t know this field well) to understand precisely how that distinction ramifies into other fields and problems. You hint at this when you talk about the appropriate “triggers for higher level response” but this is only a hint. Do you think that the technical definition of pandemic — and whether we are dealing with intra- or inter type variation — is really going to be an issue when they make decisions about whether to raise the level? I am not being skeptical, I am just curious to hear more about how precisely that would play out.
Keep talking. Very helpful Carlo…
There is an interview with a French public health official in Liberation today that is good (it seems). He points out that the masks everyone in Mexico is wearing provide no protection against viruses. What they do is minimize what is dispersed when people cough or sneeze.
The whole virulence question is again interesting. They mention it as well as “mutations” but this by itself says nothing.
Meg, Lyle and Anthony are taping Roger as we read this morning.
Thanks, Stephen, for pushing this. I wish I could explain it in more detail, but at the moment it is difficult to follow all the events in addition to all the trivial demands of the day that academic work brings with it. But here is a thought-experiment. Think about the exactly same events, exactly same numbers, same transmission rate, same case-fatality rate, but with an avian influenza virus as its cause. I think the pandemic would have been declared a week ago in that case.
I think at this point they can’t yet declare a pandemic because the political pressure is extremely high (as well as the stakes), because it’s not the expected virus subtype (and thus not the story that experts have been telling again and again), and because there have not yet been “enough” fatal cases. The technical question of classification is a part of this, but not the whole story.
In public and expert discourse, the virus has already been identified as “new,” without making explicit in what sense it is new (obviously not in terms of subtype, so then what?). The fact that it is called a “swine” flu virus seems to make all the work here. But of course, you will find in swine populations both “swine” flu viruses as well as “human” viruses. What makes a flu virus a “swine” virus and what makes another flu virus a “human” virus is largely unknown. You simply find some only in swine, or in humans and in swine, or only in humans (today.) In technical terms: this is a question of specificity (of host range), but not of immunity.
… here are the definitions. We are at least in phase 4 if not 5! But according to the WHO we still are in 3. Why is that?
Phase 4 is characterized by verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause “community-level outbreaks.†The ability to cause sustained disease outbreaks in a community marks a significant upwards shift in the risk for a pandemic. Any country that suspects or has verified such an event should urgently consult with WHO so that the situation can be jointly assessed and a decision made by the affected country if implementation of a rapid pandemic containment operation is warranted. Phase 4 indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a forgone conclusion.
Phase 5 is characterized by human-to-human spread of the virus into at least two countries in one WHO region (Figure 4). While most countries will not be affected at this stage, the declaration of Phase 5 is a strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short.
So according to the WHO phase in which we presumably are in today, nothing significantly different has happend in the past three weeks in Mexico and the US. It’s basically the same as we have been seeing over a decade with H5. Come-on!
Carlo, thanks for a wonderful discussion catalyst and follow ups. Although my research has focused on bioterrorism and not flu, and I am not an expert by any means, I don’t know if you can do that thought-experiment while holding the case fatality rate constant. There just appears to be too significant of a CFR difference between what we are seeing now and H5N1, isn’t the CFR for avian at least 1 in 2, while from the early data we are getting from Mexico seems to be more around 6 in 100. I think those numbers have seeped into the signifier ‘H5N1′ a bit and would help warrant an earlier declaration of a pandemic.
I am curious about your thoughts on Dr. Besser’s recent insistence about the CDC’s actions having no correlation to pandemic declarations (in the media call today he said something like ‘CDC’s actions are based on what is happening in the community and not what label we put on it’). He seemed to say that the stakes for pandemic declarations are higher for countries that have not yet confirmed swine cases, what are these stakes? travel/trade restrictions?
On Lyle’s construction of novelty question, which has the opposite pull to it as Carlo’s thought-experiment, the CDC is saying that this is ‘first time ever’ that two types of swine flu virus (American and Eurasian) have been found in either pigs or humans. So, while there have been documentation of avian-swine-human influenza viruses in the US preciously, this is maybe a new reassortment. Also, there are some interesting arthropod vector theories arising in the Mexican news media about the pig-human cross-over, mostly surrounding the ‘confined animal feeding operations’ outside of Mexico city.
As for Rabinow’s relayed news about the only out-bound efficacy of the tapabocas/facemasks, that really concerned me, I was hoping for some thin paper peace-of-mind (if needed) on my international flight tomorrow. The CDC is saying “facemasks and respirators may help reduce the risk of getting influenza” so maybe there is a weak in-bound preventative efficacy, thanks for the heads-up!
WHO had been saying they would wait until Tuesday to decide whether to raise the alert level from 3 to 4 (or 5). They’ve just announced that they moved the meeting up to today. It seems likely, as Carlo suggests, that they will raise the alert level. In their pandemic preparedness documents WHO states its criteria for assessing the level of alert:
(available here: http://www.who.int/csr/disease/influenza/pipguidance2009/en/index.html)
3.2.5 Providing an early assessment of pandemic severity on health
As soon as possible, WHO will provide an assessment of pandemic severity to help
governments determine the level of interventions required as part of their response. As
outlined in section 1.1, past influenza pandemics have been associated with varying
levels of illness and death.
Although making an informed assessment of severity early in the course of a pandemic
will be challenging, such an assessment will assist countries in:
- deciding whether or not to implement mitigation measures that may be potentially
disruptive;
- prioritizing the use of antivirals, vaccines, and other medical interventions;
- managing continuity of health care; and
- communicating with the media and the public and answering queries.
Pandemic severity may be assessed in many ways. One fundamental distinction is an assessment based on direct health effects as opposed to one based upon societal and
economic effects.. While societal and economic effects may be highly variable from country to country and dependent upon multiple factors (including the effects of the media and the underlying state of preparedness), WHO plans to assess pandemic severity based primarily on observable effects on health.
Available quantitative and qualitative data on health impacts will be used to estimate
severity using the three-point scale of Mild-Intermediate-Severe. As more information
becomes available, WHO will update the severity assessment. Since national
circumstances will vary in terms of disease activity and capacity to respond, caution should be exercised in directly linking severity assessment at a global level to actions at
the national level.
It is likely that information will be limited early in the pandemic while the demand for
information simultaneously escalates. If pandemic surveillance is to provide sufficient
information and data to assess severity, countries need to review their existing
surveillance capacity to address the weaknesses to be prepared for pandemic
surveillance.
also it looks like Carlo was pretty prophetic about the Pandemic definition revision. That is the only news that has leaked, that there has been a revision of the scale, as of yet.
Sorry, Twitter is telling me that ‘Reuters alerts about a new WHO scale are false’ sorry about that. That is the second misinformation from Reuters about the flu that has duped me, the first was about the archeologist that could have exposed Obama in el DF, and his alleged death the next day from ‘flu like symptoms.’ the archeologist did, unfortunately, die but much later than Reuters claimed and of possibly more complicated health issues.
But every one does seem to agree that the WHO has now raised the pandemic level to 4.
Andy–to avoid confusion, pandemic severity is not the same as the alert/threat level, is it?
My understanding was the same as Carlo’s: that Phase 4 was defined as “verified human-to-human transmission”. What has been interesting is that the CDC has declared human-to-human transmission since at least Friday, and probably has known it since even earlier. In their MMWR report on April 21 about unusual H1N1 flu diagnoses in San Diego county, they note that “The lack of known exposure to pigs in the two cases increases the possibility that human-to-human transmission of this new influenza virus has occurred”. Meanwhile, for the past ten years, the question about avian influenza H5N1 has always been if and when it will become human-to-human trasmittable. Since I believe that was never verified, there was never reason to raise the threat level.
Its quite amazing that they moved the meeting up a day. I was shocked when I read on Sunday that they arbitrarily “are going to decide on Tuesday” as if the course of the outbreak could wait for them to make the decision.
Also, as I think Carlo is indicating, according to their definitions, we should be in Phase 5: cases in much more than two countries.
One take home from a conversation with Roger Brent this morning: frustration that all we know is this is an unusual H1N1 (based on what he called ‘antediluvian’ immuno typing techniques) and don’t know the genetic sequences.
Also, why is this called a “swine flu”? While it may have emerged from pig populations, calling it a swine flu seems to minimize the autonomous ontology of the virus, as if it somehow needed to be tied to pig populations. It is now human-to-human transmissable, which seems much more significant than its animal origins.
And as I think Carlo hinted, H1N1 was human flu before it was swine flu.
Like others following this, i’m not fully up on the technical side of this, but relative to the question Steven has asked- what kind of institutional response is mobilized in relation to what kind of technical information – the BBC has been reporting about activities at the World Influenza Center in London which currently running ferret assays to determine if there are signs antigenic drift. Is this a criteria or measure for changing the WHO’s response?
Lyle – Yes, pandemic severity is different from alert level. It’s worth looking at the WHO pandemic preparedness guidance document to see what is at stake in the alert levels. It seems mainly focused on the practical task of deciding on preparedness/ response recommendations for countries: “It is important to stress that the phases were not developed as an epidemiological prediction, but to provide guidance to countries on the implementation of activities.”
Here is how they explain the phased alert system:
“This phased approach is intended to help countries and other stakeholders to anticipate
when certain situations will require decisions and decide at which point main actions
should be implemented (see TABLE 3). As in the 2005 guidance, each of the phases
applies worldwide once announced. However, individual countries will be affected at
different times. In addition to the globally announced pandemic phase, countries may
want to make further national distinctions based upon their specific situations. For
example, countries may wish to consider whether the potential pandemic virus is causing
disease within their own borders, in neighbouring countries, or countries in close
proximity.”
This is all toward answering the question of what the actual stakes are in the alert level. It seems to me that the particular actions recommended for each country (eg. containment activities; or rapid vaccine production) are the things to focus on.
I wonder if the U.S. is in general following a “preparedness” strategy regarding travel restrictions. Although U.S. officials are complaining about travel restrictions imposed ON the U.S., C.D.C. is advising against “non-essential” travel to Mexico.
http://wwwn.cdc.gov/travel/contentSwineFluMexico.aspx
I believe initial epi data was fairly inconclusive, in toto, regarding human-to-human transmission – clusters notwithstanding. Contact tracing had, as I read it, *not* generally revealed Case A infecting Case B infecting Case C. Remember: epidemiologists follow this principle religiously in helping to make H2H determinations, and it is this, I would guess, which had to date been the “limiting factor” in moving to Phase 4. The move to Phase 4 clearly suggests recent convincing epidemiological and lab evidence of H2H. I’d reiterate that cases from the last several days seem to have been primarily suspected of H2H transmission, without having been “proven.” Speaking of thresholds, thresholds for “proof” in this context might themselves prove interesting as objects of social scientific inquiry.
On another note, I am curious what active surveillance of US hospitals is going to turn up as a way to make CFRs more comparable.
Dale, yes, I agree in principle, they want to identify all the contacts and they want as much evidence as possible. But with these case numbers and the geographical spread in such a quick time, there must be human to human transmission. Also, this was already indicated quite early by the first MMWR on the cases in California and Texas, as Lyle noted.
The reference to a “lack of evidence” can also be a way of articulating other conflicts which cannot be expressed directly.
The other important thing that I read today is that the WHO argues that interventions should focus on mitigation rather than containment. So again there seems to be a sense that containment might be almost impossible at this stage. How governments will actually respond is, of course, another question.
Here’s what Keiji said yesterday according to the NYT:
“Because the virus is already quite widespread in different locations, containment is not a feasible option,†said Dr. Keiji Fukuda, the organization’s deputy director general.
Asked why the W.H.O. had waited so long to raise its alert level, Dr. Fukuda said it was done on technical grounds, that there was evidence of sustained human-to-human transmission of a new virus and movement of that virus to new areas. But he conceded that “the committee is very aware that changes have quite significant political and economic effects on countries.â€
Just a quick note on antigenic drift and antigenic shift. According to current doctrine, pandemics are caused by antigenic shift (the appearance of a new subtype of the influenza virus in the human population through mutation and/or reassortment. Examples: emergence of H1 in 1918, emergence of H2 in 1957, and emergence of H3 in 1968). Antigenic drift (intra-subtype variation through mutation and/or reassortment) is responsible for seasonal outbreaks of influenza.
The paradox is that we seem to have a pandemic today which is not caused by antigenic shift but rather by antigenic drift.
In the history of influenza, this is actually nothing new. Several pathological events have occurred which made it necessary to change the doctrine. In these cases, the definition of what counts as a subtype was simply changed …