Transmission of avian influenza viruses to and between humans.

Potential conflicts of interest: F.H. has received payment as a consultant and grant support from several pharmaceutical companies involved in the development of antiviral drugs and vaccines for influenza. The views expressed in this article are those of Dr. Croisi-er and do not necessarily reflect those of the World Health Organization. Reports of seropositivity for different avian influenza A viruses in exposed poultry workers, including the new findings reported by Puzelli et al. in this issue of the Journal of Infectious Diseases [1], and the recent instances of cross-species transmission that caused human disease [2] raise fundamental questions regarding the routes of transmission of avian viruses to and between humans, possible differences in transmission patterns between human and avian influenza viruses , and implications for prevention in those occupationally exposed to infected animals and also in health care, household , and community settings. Documentation of seropositivity for avian influenza viruses in farm workers is not a new finding [3], and previous studies have assessed human susceptibility by in-tranasal inoculation of selected avian influenza viruses [4]. However, the outbreak in Europe of H7N7 virus infection that led to many cases of conjunctivitis and 1 death resulting from viral pneumonia [5, 6], as well as the unprecedented epizootic caused by highly pathogenic avian influenza H5N1 virus in Southeast Asia, emphasize the importance of these issues. One strength of the study by Puzelli et al. is the multiplicity of the serological tests used, which included a microneutraliza-tion assay with infectious virus, a hem-agglutination inhibition (HI) assay, and a confirmatory Western blot analysis with purified H7 hemagglutinin to exclude the possibility of nonspecific cross-reactions with antibodies to human influenza viruses. Differential absorption with human influenza virus has also been utilized to confirm the presence of avian influenza virus–specific antibodies [7]. Such methods are essential to document seroposi-tivity for an avian influenza virus, particularly when concerns about extensive transmission to humans are raised, as was reported elsewhere for H7N7 virus infection in The Netherlands [8]. The possibility that the latter virus caused widespread subclinical infections in poultry workers and household contacts—and, hence, manifested efficient human-to-human transmission—was raised by 1 study that used a modified HI assay to measure antibody [8]. Similarly, the recent report of asymptomatic infection by H5N1 virus in northern Vietnam, as determined by the detection of H5N1 RNA in household contacts, requires substan-tiation by confirmatory serological testing [9], although culture-confirmed H7N3 illnesses …