Dual-use and the fatality rate of H5N1

The long-winded “Seroprevalence of Antibodies to Highly Pathogenic Avian Influenza A (H5N1) Virus among Close Contacts Exposed to H5N1 Cases, China, 2005–2008,” came out in PLoSOne this week. It is a good day for people like myself who have concerns about gain-of-function research that seeks to modify— or results in the modification of—highly pathogenic H5N1 avian influenza.

The study’s importance goes back to the controversy in 2011 and 2012 surrounding papers submitted to Science and Nature respectively by Ron Fouchier and Yoshihiro Kawaoka, in which they showed how H5N1 could be modified to transmit between mammals (in this case, ferrets). The papers were identified as cases of dual-use research of concern (DURC):

research that, based on current understanding, can be reasonably anticipated to provide knowledge, products, or technologies that could be directly misapplied by others to pose a threat to public health and safety, agricultural crops and other plants, animals, the environment or materiel (source)

The editors of Science and Nature agreed, initially, to censor the papers at the request of the National Science Advisory Board for Biosecurity. The continuing debate—following the release of modified versions of the papers—turns on a lot of things. Of note, however, is the insistence of virologists such as Morens, Subbarao, and Taubenberger, among others, that:

whatever the case, unless healthy seropositive people detected in seroprevalence studies temporally and geographically associated with H5N1 cases are all falsely seropositive, their addition to exposure denominators greatly decreases case-fatality determinations.

That is, the potential for asymptomatic and undetected H5N1 infections would lead to a far lesser case fatality rate than the current figure, which sits at the staggeringly large 60%. (For context, the 1918 “Spanish” flu that killed 50–100 million people had a case fatality rate of about 2.5%.)

Convincing the NIH, the NSABB, and the public that the H5N1 studies are safe and laudable exercises relies in part on the claim that the 60% figure isn’t all it is cracked up to be.[1] This new study throws weight behind the concern that H5N1 is really as lethal as it seems, and that it is manifestly dangerous to do things like alter its method of transmission, host range, drug resistance and so on (experiments Fouchier now wants to do on H7N9—see here and here).

Downplaying the risks of H5N1 would be just as irresponsible as it would be to claim, for example, that Fouchier’s lab engineered a supervirus;[2] we need to be mindful of the potential for good and bad uses of this research, and acknowledge the contingencies and assumptions upon which our predictions rely. The “DURC-is-safe” group, as Garrett called them today, have relied on problematising the case fatality rate of H5N1. Support for that type of claim is rapidly shrinking.

  1. In point of fact, in the last article I released on this topic, a reviewer attempted to undermine my argument using exactly such a claim. It is a really common point of contention in the literature.  ↩
  2. Which, incidentally, is what Fouchier was getting at when he said it was “probably one of the most dangerous viruses you can make” and that it was a “stupid” experiment. Words he really quickly went back on once he realised, in the words of Gob Bluth that “he’d made a huge mistake” by fear-mongering.  ↩

One thought on “Dual-use and the fatality rate of H5N1

  1. Jon Herington

    I love reading this science…brings back terrifying exams memories.

    I think one thing worth being cautious about is that this study aimed to track the seropositivity of close contacts of H5N1 patients, not the seropositivity of people who had risky contact with poultry (although 52(12%) of their serological study group did have contact with sick/dead poultry). Presumably for a virus that isn’t supposed to be human transmissible, its contact with poultry and other reservoirs that is the appropriate risk factor for sub-clinical infection. In that sense, Morens et al point about seropositivity might still stand – especially given the rates of seropositivity (~1%) that Wang et al. identified in poultry workers from their meta-analysis (http://www.sciencemag.org/content/335/6075/1463.full).

    That said, the CFR would have to be MUCH MUCH lower (i.e. >>1%) before it was no longer a hellishly dangerous pandemic candidate. That would require something like 1 clinical : 60 subclinical cases…


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