Reply to “Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited”

Lipsitch, Marc; Inglesby, Thomas V.

Assertions that wild-type H5N1 is much less than 60% lethal are not well founded. The estimate that several percent of persons in large areas of Asia were asymptomatically infected with H5N1, used to support a lower estimate of wild-type H5N1 lethality, comes from work by Wang et al. (31) which has been directly refuted by influenza serology experts and epidemiologists (32) and further refuted by a separate analysis that was similarly critical of the data used by Wang et al. (33) . We do not regard the case fatality risk (CFR) of H5N1 in naturally exposed humans as a settled issue, and well-conducted serosurveys may support the idea that asymptomatic or subclinical infections are more common than previously estimated, at least in some populations (34) . Yet for the moment there is little evidence that the observed~60% CFR in humans for H5N1 is the result of missing large numbers of milder infections, in contrast to the situation, for example of H7N9, where detected cases are thought to be a small fraction of the total (35).