Science's Influenza Special Issue

The spread of the highly pathogenic avian influenza strain H5N1 across much of the globe highlights human vulnerability to the emergence of new subtypes of the influenza virus. Contributors to the 21 April 2006 issue of Science describe ways in which we can marshal existing concern about the H5N1 strain of avian influenza to build a long-standing international infrastructure to monitor and thwart threats from such emerging infections. The special issue includes a "Review," "Perspectives," a news feature and an editorial. Also included in the issue are new studies that were recently published online by Science at the Science Express website.

From One Species to the Next

Understanding the factors that collectively limit the transmission of influenza and other pathogens from one species to another — the "host species barrier" — is a necessary step towards containing and eradicating emerging infectious diseases, according to the authors of a "Perspective" article. Individuals from two species must interact, on physical and molecular levels, in ways that are sufficient to transmit the pathogen from the donor species to the recipient species, but this is just one of the hurdles that must be cleared to get over the host species barrier.

Although there is a vast body of literature on influenza, only a few studies consider the barriers for influenza viruses to cross from one species to another. One important question that remains, according to Thijs Kuiken and colleagues, is "Which genetic changes would allow the currently circulating H5N1 virus to acquire the characteristic to spread efficiently among humans?" Despite the fact that scientists have been studying influenza in tissue culture for a long time, there are still unknown barriers at tissue and organ levels that — if understood — could help researchers predict and/or prevent the next pandemic, the authors say.

Emergence of Drug-Resistant Influenza Virus

Drugs currently available for preventing and treating influenza will play an important role as a first-line defense if a new influenza pandemic occurs, according to the authors of a "Perspective" article. But, the large-scale use of these drugs may lead to drug-resistant strains that could substantially limit the drugs' effectiveness.

Roland Regoes and Sebastian Bonhoeffer summarize recent data on the rate at which the treatment of influenza infection generates resistance as well as data on fitness costs associated with drug resistance mutations. Researchers are working to enhance their ability to predict how intensive drug use aimed at treating and preventing influenza infection in humans would affect drug resistance, the authors say. This kind of work may yield a better understanding of the consequences associated with the use of antiviral drugs as a first-line defense against a new pandemic strain.

Predicting and Preparing for Influenza

In light of the ongoing avian influenza pandemic, the threat of pandemic human influenza looms, prompting questions such as "What are the risks?" and "How can we plan?" While the inherent variability in influenza viruses makes predictions difficult, mathematical models can provide estimates for the levels of drug stockpiles needed to buy time, how and when to modify vaccines, whom to target with vaccines and drugs, and when to enforce quarantine measures, according to Perspective" author Derek Smith. These models must be tested, and this kind of model testing requires the continual gathering of data for seasonal influenza as well as exceptional influenza outbreaks. Such efforts to increase basic understanding of influenza viruses on multiple levels, including the molecular, immunological, evolutionary, epidemiological and ecological, will increase options for controlling seasonal influenza and predicting and preparing for the next influenza pandemic, regardless of whether it is imminent or many years away, according to Smith.

Influenza A Virus in Wild Birds

The authors of a "Review" article outline the unseen network of influenza among migratory birds that spans Earth. With our current limited knowledge on highly pathogenic avian influenza (HPAI) in wild birds, there is no solid basis for including wild birds in control strategies beyond physical separation of poultry from wild birds, according to Björn Olsen and colleagues. Wildfowl and shore birds are, however, thought to form the virus reservoir in nature and attempts to understand the ecology, epidemiology, genetics and evolution of influenza viruses are incomplete without taking into account the ecology of wild birds and other host species.

Dabbling ducks of the genus Anas are the most extensively monitored wild bird species for influenza. These ducks, including Mallards, have been found to be infected with influenza viruses more frequently than other birds and their migration patterns and feeding behavior could, at least partially, explain the observed rates of infection. A better understanding of the genetic variation and evolution of influenza viruses in wild birds will be useful to epidemiologists as well as those studying the interactions between influenza viruses and host species, the authors say.

Daniel B. Kane

20 April 2006