Transmission of Influenza Virus: What Is Keeping the Next Pandemic at Bay?

Introduction

We are constantly reminded of the threat of an influenza pandemic. Although it is no longer at the forefront of the news, we receive weekly reminders of avian influenza outbreaks in poultry around the world and the threat of potential human infections.

Pandemic preparedness has become a catchphrase for politicians, government agencies, and communities, both nationally and internationally. Potential vaccines and antiviral drugs are being stockpiled, and plans for distribution and immunization are being readied. In November 2005, the federal government released the National Strategy for Pandemic Influenza. This document aims to coordinate and prioritize the activities of all parts of our society, from individuals and families up to state and federal governments and agencies. Preparations are included for a possible pandemic, pandemic response, and recovery.

The influenza virus(es) prompting the fears of pandemic, the resulting media storms, and pandemic planning are primarily the highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype. Having made that statement, it is important to note that the HPAI and H5N1 designations have a minimal relationship with the infection of or disease in humans. Avian influenza virus is classified as low pathogenic avian influenza (LPAI), which causes mild or asymptomatic infections in poultry, or HPAI, which causes severe disease and is rapidly lethal in chickens.^[1,2] The H5N1 designation represents the hemagglutinin (HA) and neuraminidase (NA) types expressed by the virus.

The HA and NA types are made classically by serotyping, using monospecific antisera prepared against the 16 distinct HA and 9 distinct NA antigens, or more recently by sequencing the HA and NA genes.^[2,3] Biological features of the HPAI H5N1 viruses enable the rapid and systemic replication of these viruses and resulting deaths of poultry, providing the opportunity for exposure of humans to very high titers of avian influenza virus, and enabling potential infection of exposed humans.

The H5N1 viruses first infected humans in Hong Kong in 1997, infecting 18 individuals and killing 6.^[4] Although Hong Kong responded rapidly by culling all commercial birds on the island and contained the outbreak, the H5N1 viruses remained in reservoirs on mainland China. The now constant smolder of H5N1 influenza virus infections in poultry, waterfowl, and other avian bird species in Southeast Asia and the movement of these viruses through Asia and into Europe suggest that the H5N1 viruses are not going to disappear back into their reservoir species.

To date, there have been 381 confirmed cases in humans and 240 deaths caused by H5N1 influenza virus.^[5] Although no person can predict when a pandemic will occur or whether H5N1 HPAI will be the next pandemic influenza virus, history tells us that there will be additional influenza pandemics, and the sporadic human infections with H5N1 make these viruses a reasonable candidate. This column focuses on mechanisms of influenza virus transmission, how avian viruses can cause pandemics, and why the current HPAI viruses have not yet succeeded.