Peiris: Both SARS and avian flu are new emerging infections with dramatic impact on human health. There are interesting parallels and also differences between these two diseases. SARS arose from an animal source but adapted to transmit efficiently from human-to-human, and within weeks, spread across the world. Prior to this adaptation to efficient human transmission (which occurred in late 2002), serological evidence of human infection in those working in wild animal markets in Guangdong suggested that the SARS coronavirus continued to inefficiently infect humans, perhaps for many years. Avian flu H5N1 is still at the stage of transmitting inefficiently from the animal (avian) source to humans, which is comparable to the pre-2002 situation with SARS. The concern is that if the avian flu virus is given continued opportunity to infect humans, this virus also may adapt to efficient human transmission, resulting in a pandemic. The one major difference between SARS and an influenza pandemic is that it is unlikely that the latter will be stopped by the public health measures that successfully stopped the human SARS outbreak. This is why by August 2003—while SARS was still the hot topic of the day—Dr Guan and I re-focused our research team effort back to avian flu.

Guan: Both diseases are zoonotic infectious diseases. The emergence of SARS was initially considered as a possible pandemic of H5N1 influenza virus. This is the reason why our group was involved the research, and why the WHO influenza program leader became the coordinator for SARS.

Peiris: I will leave this to Dr Guan to address since this is his area of work.

Guan: Only one gene segment of the H5N1/97 virus remains the same as the current H5N1 virus in Southeast Asia. Most gene segments of the viruses were incorporated from other viruses circulating in this region in the past several years (from 2000 onwards). However, the main surface gene, HA gene, was derived from the same precursor, A/Goose/Guangdong/1/96. This HA gene keeps evolving all the time. There is only 94% homology between the precursor virus and current strains. This will directly impact the effect of the vaccine. We also found that viruses from different regions have different antigenic aspects.

Peiris: As indicated above, once it emerges, pandemic influenza is likely to have a much greater impact that SARS did. Pandemic influenza will not be stopped by the public health measures used to stop SARS transmission in the community. From past experience we know that influenza pandemics will sweep the world within the first eight to nine months of its emergence. The spread will possibly be much faster now, with the great increase in air travel. The major unknown is the severity of human disease associated with such a pandemic. The pandemic of 1968 was relatively mild while that of 1918 was associated with a high severity of clinical disease. What we know about human disease associated with H5N1 so far is not too reassuring. Of course H5N1 may become less virulent to humans as it adapts better to human transmission, but this is not inevitable.

Guan: Certainly pandemic flu, as its original hosts are different. We knew SARS virus mainly harbored in wild animals in the markets, such as civets—but there are only a small number of those animals. After closing the wildlife markets, the SARS virus did not come back in the last year. We also averted a second outbreak in early 2004. However, avian influenza has millions and millions of hosts and those hosts may migrate long distances just within one day. So, it is much more difficult to contain bird flu than SARS.

Peiris: The major points to be addressed are:

1. What animal influenza viruses pose the greatest pandemic threat? H5N1 is not the only contender as the cause for the next influenza pandemic. This is important for pandemic preparedness.
2. To better understand the characteristics that define the potential for interspecies transmission of viruses, i.e. the potential for viruses to jump species barriers.
3. To better understand why a virus like H5N1 causes such severe disease in humans while the normal human flu virus does not, i.e., to better understand the pathogenesis of H5N1 disease.

Guan: Keep doing surveillance studies on both human and animal aspects. Ideally, we could identify the early pandemic strain if possible, or the indication. We could also try to identify the molecular basis for interspecies transmission, understanding the mechanism of interspecies transmission. Another field our group will keep working on is those novel emerging infectious agents in this region. The development of a vaccine and diagnostic reagents has become one of the important parts of my research as this is currently important for pandemic preparedness in the world.