The fatality rate for human infections with avian influenza H5N1 is widely quoted at >50%, based on the number of deaths among the fewer than 600 cases confirmed by the World Health Organization. Wang, Parides, and Palese suggest that this number is an overestimate:
…the stringent criteria for confirmation of a human case of H5N1 by WHO does not account for a majority of infections, but rather, the select few hospitalized cases that are more likely to be severe and result in poor clinical outcome.
To address this problem, the authors summarized the results of serological surveys in which human sera were examined for the presence of antibodies to influenza H5N1 virus. Because antibodies are part of our immune defenses, they are a good indicator of a previous infection.
The authors searched the scientific literature and identified 20 studies in which human sera were examined for the presence of H5N1 antibodies according to WHO guidelines (a 4-fold or greater increase in neutralizing antibody titer in paired acute and convalescent sera, with the convalescent serum having a titer of ‰¥1:80, or an antibody titer of ‰¥1:80 in a single serum collected at day 14 or later after onset of symptoms and a positive result using a different serological assay).
Studies that used the WHO criteria included 7,304 study participants. Rates of seropositivity were from 0 – 5.3%, with one study reporting 11.7% positivity. The meta-analysis yielded a seropositivity rate of 1.2% (95% confidence interval 0.6% – 2.1%). When only poultry workers were considered, the seropositivity rate was 1.4%.
Other studies were separately analyzed that did not utilize WHO guidelines; these included 6,774 participants and yielded a seropositivity rate of 1.9% (95% confidence interval 0.5 – 3.4%).
A total of 12,677 study participants from 20 studies were included in this meta-analysis, of which 1-2% had evidence for prior H5N1 infection. The authors conclude:
…avian H5N1 viruses can cause a rate of mild or subclinical infections in humans that is not currently accounted for and thus, the true fatality rate for H5N1 influenza viruses is likely to be less than the frequently reported rate of more than 50%.
It seems very clear that standardized, large scale studies are needed to determine the real number of human H5N1 infections. This information is critical for assessing the actual threat of H5N1 influenza for humans.