Flu Outbreak Shows How Hard They Are to Predict

by Aalok Mehta

April 29, 2009

The appearance of the new flu strain swine influenza A (H1N1) highlights the difficulties faced by health officials who try to prevent flu outbreaks via vaccines that activate the human immune system. At their most benign, flu viruses kill hundreds of thousands yearly, but occasionally a new strain causes a global pandemic of crippling severity, such as the infamous 1918 Spanish flu that claimed an estimated 50 million lives.

“The question is, will this very virulent flu become more virulent, more than the three strains we have prepared vaccines for?” says Peter Palese, chair of the microbiology department and professor infectious diseases at Mount Sinai Medical Center. “It’s a little bit too early to tell.”

Every year the World Health Organization (WHO) chooses the three current strains of flu it believes pose the greatest risk to humans, which then form the basis for a seasonal flu vaccine. But the process to make the vaccine, culturing weakened forms of these strains in chicken eggs, takes approximately six months. So the WHO must make its selections well in advance of each hemisphere’s winter flu season, despite the potential that it might have chosen wrong.

 The vaccines work by stimulating a reaction to hemagglutinin or neuraminidase proteins expressed on the outer surface of the virus. Unfortunately, these components of change rapidly, either through mutation or through genetic swaps with other strains of flu virus, rendering each vaccine good for only about a year.

Swine flu—which, despite its name, is actually believed to contain genetic components from avian, human and swine flu strains—was not one of the selected strains this year, and the current vaccine is unlikely to have any protective effect against it, Palese says.

He adds, though, that current methods of manufacturing vaccines will result in a vaccine that will block the new strain—given enough time. “There is nothing problematic here. It’s not unique, not some new beast,” he says. “But the vaccine makers have really geared up for the three strains selected for 2009-10, because this comes very late in the season.”

Thus far, the WHO has advised vaccine manufacturers to keep making the seasonal vaccine for the 2009-10 flu season, but also to prepare a weakened form of swine flu for mass vaccine production in case it is needed.

How deadly?

The WHO’s measured response reflects that scientists still have very little idea what this flu strain will do next—or even what it is doing now.

Part of the problem is a lack of appropriate testing materials. Though the U.S. Centers for Disease Control and Prevention is rushing out test kits, verifying that a person has swine flu is a slow process in many areas. In Mexico, for instance, the death toll is largely unofficial; only 20 of the more than 150 suspect deaths so far have been confirmed as swine-flu-related. Those uncertainties are even greater when it comes to gauging the total number of infections, as many people who contract the virus will have mild or no symptoms.

“There are a number of fatalities associated with swine influenza, but no one knows if they are really A(H1N1), and we don’t know how many subclinical infections are occurring,” Palese says.

Scientists are closely watching the type of people succumbing to the disease’s effects. “It looks like a series of young persons that have been dying,” says Jacques Banchereau, director of the Baylor Institute for Immunology Research in Dallas. “This is reminiscent of the old Spanish flu—an interesting phenomenon in which the disease caused too strong an immune reaction.”

For a long time, one of the most puzzling aspects of the 1918 flu was why it disproportionately affected otherwise young, healthy people, who should have been most able to resist the disease. Eighty-eight years later, in a 2006 study in the journal Nature, scientists reported that the virus seems to induce a cytokine storm, a potentially fatal immune overreaction that makes a strong immune system a liability instead of a benefit.

“But we know very, very little” about whether swine flu is doing the same thing, adds Banchereau, who received a grant from the Dana Foundation between 2001 and 2006 to develop an immunodeficient mouse that could serve as a testing model for flu strains and potential vaccines.

WHO alert

Despite the uncertainties, officials across the world are preparing drastic emergency plans, including closing down schools, curtailing travel and quarantining infected people. Officials in the United States and some other countries have advised their citizens to cancel all unnecessary trips to Mexico, for instance.

But officials also agree that the flu has already spread too far to focus only on eradicating the disease. “Given the widespread presence of the virus … containment of the outbreak is not feasible,” WHO Director-General Margaret Chan said in an April 27 statement. “The current focus should be on mitigation measures.”

The WHO also raised its pandemic threat level to four for the first time on Monday, stating that “Phase 4 indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a forgone conclusion.” Phase five would indicate an imminent pandemic and phase six that a full-blown pandemic is already under way.