Understanding Swine Flu

By Henry I. Miller

The extent and impact of the swine flu epidemic, which appears to have originated in Mexico and spread rapidly to a dozen countries and parts of the U.S., is still unknown. The epidemiology of such disease outbreaks is rather like a jigsaw puzzle, and we are now at the stage where the picture is intriguing even if we're not sure what we're seeing.

We do know the number of cases in Mexico exceeds 1,995, there have been at least 149 deaths, and there have been 20 cases in five U.S. states (with no fatalities as yet). And that the outbreak causes us to confront complex issues that encompass medicine, epidemiology, virology and even politics and ethics.

These events demonstrate that good surveillance is needed in order to detect early on that a new infectious agent, transmissible between humans, has emerged. Unfortunately, conditions in many countries are conducive to the emergence of such new infectious agents, especially flu viruses, which mutate rapidly and inventively. Intensive animal husbandry procedures that place poultry and swine in close proximity to humans, combined with unsanitary conditions, poverty and grossly inadequate public-health infrastructure of all kinds -- all of which exist in Mexico, as well as much of Asia and Africa -- make it unlikely that a pandemic can be prevented or contained at the source.

In theory, a flu pandemic might be contained in its early stages by performing "ring prophylaxis" -- aggressively using antiflu drugs, vaccines and quarantines to isolate relatively small outbreaks of the new infectious agent. Addressing H5N1 avian flu in 2005, Johns Hopkins University virologist Donald S. Burke said, "it may be possible to identify a human outbreak at the earliest stage, while there are fewer than 100 cases, and deploy international resources -- such as a WHO [World Health Organization] stockpile of antiviral drugs -- to rapidly quench it. This 'tipping point' strategy is highly cost-effective."

But a strategy can be "cost-effective" only if it is feasible. Early ring prophylaxis might work in Minneapolis, Toronto, Singapore or Zurich. In places such as Indonesia, China and Mexico, however, the expertise, coordination, discipline and infrastructure are lacking. Moreover, there is no vaccine available to prevent infection of humans by the new H1N1 swine flu (or by H5N1 avian flu, for that matter).

The rapid and constant movement of goods and people around the world makes early containment virtually impossible. We saw this with the SARS (Severe Acute Respiratory Syndrome) epidemic in 2003: Within a matter of weeks, the disease spread rapidly from southern China to infect individuals in some 37 countries, killing about 800.

In the current swine flu outbreak, New York City high-school students apparently brought the virus back from Mexico and infected their classmates. All six cases so far reported in Canada were connected directly or indirectly with travel to Mexico.

Flu viruses can be directly transmitted (via droplets from sneezing or coughing) from pigs to people, and vice versa. These cross-species infections occur most commonly when people are in close proximity to large numbers of pigs, such as in barns, livestock exhibits at fairs, and slaughterhouses. And, of course, flu is transmissible from human to human, either directly or via contaminated surfaces.

Pigs are uniquely susceptible to infection with flu viruses of mammalian and avian origin. This is of concern for a couple of reasons. First, pigs can serve as intermediaries in the transmission of flu viruses from birds to people. And when avian viruses infect pigs, they adapt and become more efficient at infecting mammals -- which makes them more easily transmitted and dangerous to humans.

Second, pigs can serve as hosts in which two (or more) influenza viruses infecting an animal simultaneously can undergo "genetic reassortment," a process in which pieces of viral RNA (the virus's genetic material, similar to DNA) are shuffled and exchanged, creating a new organism. The influenza viruses responsible for the world-wide 1957 and 1968 flu pandemics -- which killed about 70,000 and 34,000, respectively, in the U.S. -- were such viruses, containing genes from both human and avian viruses.

Experience shows that attempts to stem the spread of an outbreak may actually exacerbate it. In 2006, China's chaotic effort to vaccinate 14 billion chickens to control avian flu was compromised by counterfeit vaccines and the absence of protective gear for vaccination teams. This likely spread contagion by vaccinators who carried infected fecal material on their shoes from one farm to another.

The situation in Mexico resembles the scenario we might expect for an outbreak of a major human-to-human pandemic in its earliest stages: a large number of illnesses among social and family contacts of victims; infection of health-care workers and patients in hospitals where the victims are treated; and the rapid spread of confirmed cases from an initial region to other countries as people infected by the virus travel while it is incubating, but before they become seriously ill.

Because they have been stockpiled for use in the event of an avian flu pandemic, large amounts of the antiflu drugs Tamiflu and Relenza are available. However, they must be administered during the first couple of days after symptoms begin to be an effective treatment. They can also prevent the onset of the disease if administered in adequate doses prior to exposure. The danger of using antiflu drugs in poor countries with inadequate public-health facilities such as Mexico is that they may be administered improperly and in suboptimal doses, which would promote viral resistance and intensify an outbreak.

If the swine flu outbreak becomes a pandemic with a high rate of severe complications (such as pneumonia) and death, we will need to be smart, nimble and flexible. That will involve triage on many levels -- including decisions about which patients are likely to benefit from scarce commodities such as drugs and ventilators -- as well as "social engineering" determinations about issues such as mandatory quarantine, the canceling of public events, shutting airports and closing our southern border. Let's hope it doesn't come to that.

Dr. Miller, a physician and molecular biologist, is a fellow at Stanford University's Hoover Institution. He is a former flu researcher and was an official at the National Institutes of Health and the Food and Drug Administration from 1977 to 1994.

Source : online.wsj.com