Why There May Never Be a Bird-Flu Pandemic

Unlike other flu viruses that multiply in the throat -- making it easy to spread through coughing -- the H5N1 avian-flu virus prefers to replicate much deeper in the lungs. Clips from WSJ:

Using tissues from human cadavers, researchers at the Erasmus Medical Center in Rotterdam studied which cells the bird virus would become attached to. According to Thijs Kuiken, a veterinary pathologist who directed the research, H5N1 attached to cells deep in the lung, but not cells in the throat, where human-flu viruses multiply. The study appears in the journal Science.

Dr. Kuiken called the finding a possible explanation for why the avian virus doesn't jump easily between people. "It must reach the lower respiratory tract to replicate, and it's harder to spread by coughing and sneezing," he said.

Other doctors questioned that conclusion, saying that patients with such infections were likely to cough more heavily. "I don't think it directly affects the transmissibility just because it's in the lower respiratory tract," said Nikki Shindo, an influenza expert at the World Health Organization who has studied human cases, most recently in Turkey.

Dr. Shindo said that if the virus has to reach deep into the lung before causing an infection, that could make it harder to catch.

In a separate study released yesterday by the journal Nature, a research group headed by Yoshihiro Kawaoka of the University of Wisconsin-Madison reached similar conclusions after analyzing the specific molecules on human cells to which influenza viruses attach.

They found that molecules preferred by H5N1 are expressed mostly by cells deep in the lung. To spread between humans, the virus would need to adapt in a way that enabled it to attach to a different type of molecule present in cells higher in the respiratory tract.

Countering bird-flu hysteria, today's NYT adds additional detail regarding the relatively low likelihood that the current virus will mutate into a more virulent strain:

Though H5 may seem only a couple of steps from transmissibility among people, many virologists believe mutations in several other genes would be necessary as well, even though those changes are not yet well understood.

Viruses find it difficult to switch hosts, and though they may quite often cause outbreaks in just a few individuals, "viruses that produce a self-sustaining chain of transmission in the new host appear rare," Dr. Kawaoka writes in the current Annual Review of Microbiology. "Most of these transfers are dead ends," he said.

The H5 virus has been present in the human population since the late 1950's, said Dr. [Paul A.] Offit of Children's Hospital [in Philadelphia], but has never acquired the full set of mutations needed to set off a pandemic. Such epidemiological evidence "should make us feel safe that there's a substantial barrier," he said, noting the small number of people who have been infected.
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Peter Palese, a virologist at the Mount Sinai School of Medicine, said he did not believe the H5 virus could infect people except when they were exposed to large doses, for example, by sleeping in the same room as chickens. "I feel strongly that H5 has been around in humans for a long time and never caused a pandemic, suggesting that this is not the virus which is likely to be the next pandemic," he said.