Ferret-Transmissible Influenza A(H5N1) Virus: Let Us Err on the Side of Caution

Abstract

The recent experiments with highly pathogenic avian influenza A(H5N1) virus conducted in the laboratories of Fouchier and Kawaoka have set off a debate about whether it is appropriate to publish all of the details of these experiments publicly and about how the viruses generated in these labs should now be handled. A wide range of opinions has been expressed, both for and against restrictions on publishing this work and on working with these viruses. I would like to discuss some ideas put forth as arguments against such restrictions. First, it has been suggested that H5N1 is probably not a particularly dangerous virus and that the official WHO case fatality rate (CFR) of approximately 60% is almost certainly a vast overestimate (1–3) (“likely orders of magnitude too high” [1, 3]). This claim is based on the findings of several human seroprevalence studies conducted in several East and Southeast Asian countries since the emergence of H5N1 as a zoonotic pathogen, reporting up to 9.1% prevalence of H5N1 antibodies (1, 2). The rationale would be that if up to 9% of the population in enzootic regions—many millions of people—has been infected with H5N1 and survived, whereas there have been only a few hundred fatal cases, as tallied by the WHO, then the true CFR could be vanishingly small. However, there are methodological concerns about some H5N1 seroprevalence studies; it has elsewhere been estimated from seroprevalence studies that meet WHO H5N1 serology criteria that fewer than 0.5% of the study subjects (26 out of 5,333 participants) are positive for H5N1 antibodies (4). More seroprevalence studies are clearly needed. But if the true seroprevalence is approximately 0.5%, on average, in enzootic regions, then …