Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control.

Influenza A is a viral disease of global dimension, presenting with high morbidity and mortality in annual epidemics, and in pandemics which are of infrequent occurrence but which have very high attack rates. Influenza probes reveal a continuing battle for survival between host and parasite in which the host population updates the specificity of its pool of humoral immunity by contact with and response to infection with the most recent viruses which possess altered antigenic specificity in their hemagglutinin (HA) ligand. HA ligand binds the virus to the cell to bring about infection. Viral survival relies on escape from host immunity through antigenic alterations in nature which arise through genetic drift by point mutation principally of the HA gene, or through genetic shift by reassortment exchange of the HA ligand with that of viruses retained in avian species. Partial control of influenza is by use of killed whole, subunit, or possible live virus vaccines, all of which rely on worldwide surveillance to provide early detection of the altered immunologic specificity of the next virus to come. Future global surveillance may be aided by studies of sampled viral isolates in laboratories having capabilities for accelerated genetic sequencing and for automated rapid throughput analyses as well. Influenza vaccines of the future must be directed toward use of conserved group-specific viral antigens, such as are present in transitional proteins which are exposed during the fusion of virus to the host cell. Chemotherapy, though still primordial, must eventually provide the ultimate solution to vaccine failures. Probing the enigma of the severe influenza pandemic of 1918-1919 is an exciting contemporary venture in which genetic reconstruction of the viral genome from surviving archival RNA is being conducted with great success. Present evidence reveals successive recycling in pandemics, of only 3 of the 15 possible avian viral HAs. Pandemics are believed, conventionally, to be derived solely by rare events in which wild viruses of man acquire a new HA ligand of avian origin. There might be an alternative possibility involving a periodicity in selective control by the host population itself, in its receptivity or rejection at a particular time of particular reassortant viruses which might be created more frequently in nature than we are presently aware. This hypothesis, though remote, provides a different way to view and to probe the enigma of pandemic influenza.