Mexico's Mystery: Why Is Swine Flu Deadlier There?

By Sarah Williams

The swine-flu virus continued its gradual global march on Tuesday, prompting countries to strengthen efforts to stem its spread, while President Barack Obama asked Congress for $1.5 billion in supplementary spending to prepare for a possible swine-flu pandemic and installed the newly confirmed Secretary of Health and Human Services, Kathleen Sebelius, to help lead the fight against the disease. In the U.S., the caseload rose to 67 across five states — 45 of them in New York City, where health officials are investigating two new possible outbreaks at city schools — with more virus samples awaiting laboratory confirmation. New Zealand and Israel confirmed their first cases, while Canada, the U.K. and Spain saw small upticks in their swine-flu caseloads.

Several countries tightened border controls and discouraged travel to affected areas — Cuba suspended all flights to and from Mexico — but the World Health Organization kept the pandemic alert level at Phase 4, still two phases below a full pandemic. Outside Mexico, the apparent epicenter of the A/H1N1 virus, there have been no deaths confirmed from the flu and relatively few hospitalizations, and health officials continued to preach the need for a calm response. "What we see in the United States, or have been seeing so far, has been milder," said Richard Besser, the acting director for the Centers for Disease Control.

But health officials also cautioned that the U.S. caseload, including fatalities, would rise, with ongoing surveillance. "We expect to see more cases and we expect to report on them," says Besser. "As this moves forward, I fully expect that we will see deaths from this infection."

Still, Mexico seems to be experiencing a very different — and much scarier — outbreak than the rest of the world. More than 2,000 suspected swine-flu cases have been reported in several Mexican states, with more than 150 deaths. Those numbers are still preliminary and are expected to rise as blood samples from Mexican patients continue to be tested for the A/H1N1 swine-flu virus. Lack of laboratory capacity to run the time-consuming blood tests has so far held up the confirmation of cases there.

On Tuesday the government of Mexico City ordered gyms, discos, theaters and all sit-down restaurants (excluding those that serve only take-out) closed until at least May 6, in an effort to limit public gatherings and the spread of the virus. As epidemiologists swarm the country in an effort to trace the virus's spread, the big question remains: Why is the disease seemingly so much more deadly in Mexico than anywhere else? "This will be the object of a great deal of research and attention," said Keiji Fukuda, the interim director-general for health, safety and environment for the World Health Organization (WHO). "But we can't say why there seems to be a difference."

The WHO will convene an expert panel on April 29 to attempt to answer that question, but one way to begin is to look at where the virus originated. Epidemiologists appear to be homing in on a possible ground zero in the Mexican Gulf Coast state of Veracruz, in a town called Perote, which is home to a large pig farm owned by the U.S. company Smithfield Foods. Flu-like cases began popping up there in early April, before the first confirmed case in Mexico on April 13.

But the truth is that even though the virus is referred to as swine flu, researchers do not yet know for sure that the A/H1N1 virus actually originated in pigs. There's been no evidence yet of pigs getting sick in either Mexico or the U.S. (Despite several countries' bans on pork imports, it's important to remember that the disease cannot be contracted by eating pork.) The original reservoir for flu viruses is actually wild birds, which can spread infection to domestic birds and people — as we saw with the H5N1 avian flu in Asia — and to pigs. Pigs make particularly good biological mixing bowls since they can be infected by bird-, swine- and human-flu viruses and provide a hospitable environment for the viruses to swap genes and create entirely new strains in a process called reassortment. That is what may have happened with the A/H1N1 swine-flu virus, which contains genes from bird-, pig- and human-flu viruses. "When you get a large concentration of pig farms, people, wild birds and poultry, these things do happen," says Peter Daszak, the president of the Wildlife Trust and an expert on emerging diseases.

In recent years, since the ongoing H5N1 bird-flu virus first surfaced, health officials have focused mostly on Asia as the breeding ground for the world's next pandemic flu virus. But Daszak points out that Mexico, where people, pigs and poultry can exist in close proximity, is an overlooked hot spot for new viruses. Given the booming global livestock trade — more than 1.5 billion live animals have been shipped to the U.S. from all over the world in the past decade — it's possible that the A/H1N1 virus originated in an Asian bird that was exported to Mexico, where it may have reassorted in a pig before infecting people. Far more investigation is still needed, but it's clear that while U.S. officials were looking for flu exports from Asia, they should have also improved surveillance of their southern neighbor. "I think it might have been possible to prevent it," says Daszak. "We should be paying more attention to our own backyard."

Now that the swine-flu virus seems well established in human beings, containment is no longer an option. The public health response must be to slow the spread, which means getting a better handle on the virus. While the difference in severity between Mexico and U.S. cases would suggest that there are different viruses affecting the two countries, researchers have genetically sequenced swine-flu viruses from both Mexican and American victims, and "we see no difference in the viruses infecting sick people and less-sick people," said Fukuda. And even if there were genetic differences, it wouldn't necessarily mean much — scientists still don't know exactly which genes do what on flu viruses.

The Mexican deaths may also be attributable to some underlying coinfection or health problem that is simply not present in the U.S. cases — but that will require more investigation to uncover.

It's also possible that A/H1N1 began life in Mexico especially virulent — that country has apparently been grappling with the virus for weeks longer than the U.S. has — and evolved to become less dangerous by the time it crossed the border. That would not be an unusual evolutionary device, since viruses that are too deadly cannot survive if they kill off their host before being given a chance to spread. "It's fairly common in epidemics to see a trade-off between the ability to cause severe death and transmissibility," says Steven Kleiboeker, a virologist and the chief scientific officer for ViraCor Laboratories. The A/H1N1 virus may be attenuating itself as it spreads from person to person, becoming easier to catch but less dangerous.

The WHO, however, says that so far the virus appears to have stayed relatively stable during the chains of transmission, so it may not be mutating much. Still, the virus's current relatively weak state does not guarantee that it won't return later, much more virulent — which is exactly what happened in the 1918 flu pandemic that killed at least 50 million people worldwide. As the flu season comes to an end in the northern hemisphere, it may lead to a natural petering out of new swine-flu cases in the U.S. But the strain may continue to circulate aggressively in the southern hemisphere, which is just now entering its flu season, and then return to the north next winter.

Any conclusions now will be premature, because we still don't know what we're looking at. Experts predict we'll eventually begin to see fewer new cases in Mexico, as lab results separate real swine-flu infections from normal respiratory disease. Meanwhile, the anticipation of more cases and deaths in the U.S. has already been begun to be borne out. As the CDC's Besser himself has pointed out, swine flu is going to be a marathon, not a sprint — and we've only just gotten started.