MKAILVVLLY

by Roderick

Those of you who do not live directly beneath a rock may have heard about this whole “swine flu” thing. Unfortunately, there is a considerable amount of misinformation and confusion in the public consciousness, and the media at large seems not to be helping much in the panic-mitigation department.

So before you start building your vault, a few points to keep in mind:

1. First of all, calm down.

2. There is still no compelling reason to believe that this strain, influenza A(H1N1)1, is significantly more virulent than a typical seasonal influenza.

Your run-of-the-mill flu season has a case-fatality ratio of very roughly 0.1%, or 32% of hospitalizations [1]. Let’s narrow that to the 19-to-64 demographic, which could be most susceptible to this current outbreak (an unusual pattern seen in pandemic flus and likely caused by an overly robust immune response in healthy adults [2]), and is least susceptible to the seasonal flu. Within that population, CFR is about 0.03%, or 7% of hospitalizations [1]. Past influenza pandemics have had CFRs of anywhere from 0.1% in the 1957 and 1968 outbreaks to 2.5%2 in the 1918 “Spanish flu” [3].

In contrast, the CFR in the case of influenza A(H1N1) could be anywhere from 3.1% (an upper bound, based on a maximum of 8 laboratory-confirmed influenza A(H1N1) deaths out of a minimum of 257 laboratory-confirmed influenza A(H1N1) cases worldwide, from WHO figures available at time of writing) to 0.0016% (a very conservative lower bound, based on an approximate hospitalization rate of 0.4% of all cases in the 19-64 demographic in a typical flu season [1], with which an attack rate was extrapolated from 2000 estimated hospitalizations in Mexico).

Using figures that are quite popular in the press gives a CFR of about 7.5% in Mexico (some 150 deaths in 2000 hospitalizations, the latter very dubiously assumed to be equal to the number of cases). Because of the unreliability of the “suspected” case count in Mexico, I am not convinced that this particular CFR estimate is useful at all, even as an upper bound. It’s far more likely that the actual CFR falls somewhere between 0.0016% and 3.1%.

All of these numbers don’t tell us very much (except that it is highly unlikely that this is some epic killer virus), but that’s exactly the point. Just because (thanks in large part to the surveillance infrastructure put into place in the wake of the “avian flu” panic) this (potential) pandemic has been spotted, there is no reason to assume that we have any solid evidence suggesting that the virulence of this pathogen is particularly high. However, this may very well change as time goes on and as the situation becomes clearer, and it certainly does not mean that the virus is not dangerous.

3. Virulence is not the same as pathogenicity. Perhaps more precisely, the concepts are not the same, though the terms may often become scrambled in the fray. The salient point is that while influenza A(H1N1) has proven highly pathogenic (i.e. it is highly infectious and spreads rapidly), there is not much evidence to suggest that it is especially virulent (i.e. it has not been associated with unusually high mortality or morbidity). So while governments everywhere are preparing for the possibility of a pandemic, the severity of the disease (to wit, the “causing serious illness” criterion from the linked WHO document) is far from clear at this point. And hopefully I was able to convince you in Point 2 that there is as yet no reason to suspect any greater virulence from this strain than a typical seasonal flu strain.

4. Influenza A(H1N1) has a few key differences to Severe Acute Respiratory Syndrome (SARS) and influenza A(H5N1) or “avian flu”. For one, both SARS and avian flu were much deadlier; the SARS outbreak in Hong Kong had a CFR of about 14-17% [4], while the avian flu has a CFR of something like 14-33% [3]. However, avian flu never demonstrated efficient human-to-human transmission, which made it a very deadly disease that was unlikely to spread quickly. Likewise, SARS has never been observed to be contagious before the onset of symptoms, which significantly increases the likelihood that a person at risk of transmitting SARS can be identified by basic surveillance. Influenza A(H1N1), while appearing (for now) to be far less virulent than either of these two recent serious respiratory disease outbreaks, is also considerably more likely to spread rapidly and become pandemic.

5. There is a lot of talk in the news about “suspected” and “probable” cases of influenza A(H1N1). When these words are used by a media outlet, then frankly all bets are off. On the other hand, if a news report quotes a health official referring to a case as “probable” or “suspected,” that official is (hopefully) adhering to the CDC’s Case Definitions for Infection with Swine-origin Influenza A (H1N1) Virus (S-OIV):

A confirmed case of S-OIV infection is defined as a person with an acute febrile respiratory illness with laboratory confirmed S-OIV infection at CDC by one or more of the following tests:

  1. real-time RT-PCR
  2. viral culture

A probable case of S-OIV infection is defined as a person with an acute febrile respiratory illness who is positive for influenza A, but negative for H1 and H3 by influenza RT-PCR

A suspected case of S-OIV infection is defined as a person with acute febrile respiratory illness with onset

  • within 7 days of close contact with a person who is a confirmed case of S-OIV infection, or
  • within 7 days of travel to community either within the United States or internationally where there are one or more confirmed cases of S-OIV infection, or
  • resides in a community where there are one or more confirmed cases of S-OIV infection.

You can make of that what you will. It seems to me that there is probably no logistical barrier preventing health care entities other than the CDC from confirming the influenza A(H1N1) subtype, except for one reason or another it doesn’t count as “confirmed” unless the CDC does it.

6. When I first began considering and looking into the actual severity of the whole “swine flu” panic, I thought exactly the same thing that Obama said earlier this week: this flu outbreak (and likely pandemic) is, based on the information we currently have, a cause for concern but not alarm.

If there is one good thing that has come out of what is arguably a gross overreaction by the American media, it is a heightened awareness of the importance of public health and good hygiene. So remember kids, listen to the President and wash your hands.

References

[1] Weycker, D. et al. Population-wide benefits of routine vaccination of children against influenza. Vaccine 23, 1284-1293 (2005).

[2] Kobasa, D. et al. Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature 431, 703-707 (2004).

[3] Li, F. C. K. et al. Finding the real case-fatality rate of H5N1 avian influenza. J Epidemiol and Community Health 62, 555-559 (2008).

[4] Jewell, N. P. et al. Non-parametric estimation of the case fatality ratio with competing risks data: an application to Severe Acute Respiratory Syndrome (SARS). Statist Med 26, 1982-1998 (2006).


1I have used the nomenclature preferred by the World Health Organization as of 30 April 2009.

2The 2.5% CFR figure for the 1918 pandemic, though almost canonical, seems highly questionable given the estimates of 20-100 million deaths at a time when the world had a population under 2 billion. In any case, data from that pandemic are likely iffy at best.

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