Children’s Hospital study links deaths to post-flu issues

With four major books devoted to the topic in the last decade, most people have now heard of the 1918 flu pandemic, which killed nearly 50 million people around the world.

What they may not know, however, is that very few of those victims died of the flu itself.

Many historians now believe 95 percent of those deaths were caused by secondary bacterial pneumonia, which swept in after people's bodies had been weakened by the flu virus.

And even though bacterial pneumonia is not as big a killer in today's flu epidemics, mainly due to the advent of antibiotics, it is still a major threat.

Now that the World Health Organization has formally declared the new H1N1 swine flu as a global pandemic, with 29,000 cases and at least 144 deaths in 74 countries, researchers said the medical community and the public need to remain alert to the dangers posed by bacterial infections, particularly from strep pneumoniae.

Dr. Kathleen Sullivan, chief of allergy and immunology at Children's Hospital in Philadelphia, published a study this month in the Journal of Leukocyte Biology showing that in many children who die from flu complications, the virus paralyzes the part of their immune systems designed to protect them against bacterial invaders.

She estimated that in one-third of the children who die after flu infections, the virus immobilizes cells known as toll-like receptors, which are designed to alert the rest of the immune system to attack bacterial pathogens.

A common pattern in those children, she said, is that they seem to be recovering from the flu. Then, about a week after their first symptoms appear, they suddenly get much sicker and rapidly weaken -- a sign of the bacterial onslaught.

For several years, doctors have been advised not to prescribe antibiotics for colds and other viral infections because the drugs are ineffective against those ailments, and end up making more bacteria resistant to antibiotics.

But in the case of flu epidemics, Dr. Sullivan said, "I think the most helpful thing to come out of our study is, if a child has had the flu for five to seven days and is now getting worse, I think doctors could be more generous with antibiotics in that situation."

While children seem to be especially vulnerable to coming down with the new swine flu, they still make up only a tiny fraction of the 36,000 Americans who die in an average year from flu complications.

Almost all victims are elderly patients, and 75 percent to 85 percent of them die because they have weakened immune systems or have heart and lung conditions that make them unable to cope with the flu virus.

But even among older adults, an estimated 15 percent to 25 percent die from bacterial infections, said Dr. Jonathan McCullers, a flu specialist at St. Jude Children's Research Hospital in Memphis, Tenn.

And among healthy, younger adults, from teenagers to middle-aged people, bacterial pneumonia and sepsis are by far the biggest cause of hospitalization and death, added Dr. Ralph Tripp, a flu researcher at the University of Georgia.

The danger zone for younger adults is about a week after the initial infection, Dr. Tripp said.

"It's during this window that if you get a secondary bacterial infection, it can push you over the edge. That's really where I think the tipping point is," he said.

In adults, Dr. Sullivan added, viral pneumonia caused directly by the flu is usually much milder than bacterial pneumonia.

Historians studying the 1918 flu pandemic have detected a delayed illness pattern that points to bacterial pneumonia as the major killer.

Fewer than 5 percent of the 1918 deaths occurred during the first three days of illness, and the median time for the onset of serious sickness was seven to 10 days after initial infection, according to a study done last year by Dr. John Brundage, of the Armed Forces Health Surveillance Center in Silver Spring, Md.

That's a clear sign of bacterial infections, as John M. Barry described in his 2004 book, "The Great Influenza: The Epic Story of the Greatest Plague in History:"

"Ten days, two weeks, sometimes even longer than two weeks after the initial attack by the virus, after victims had felt better, after recovery had seemed to begin, victims were suddenly getting seriously ill again. And they were dying.

"The virus was stripping their lungs naked of their immune system ... bacteria were taking advantage, invading the lungs, and killing."

Bacterial infections exploded in the 1918 pandemic largely because there weren't effective antibiotics to fight them. But even today, the events of 90 years ago may hold important lessons, Dr. Brundage wrote.

Flu vaccines and antiviral medications such as Tamiflu obviously limit the severity of flu and help to prevent secondary infections, he wrote, but they may not be widely available in developing nations.

In those parts of the world, Dr. Brundage wrote, among the globe's poorest populations, giving people the new vaccine against strep pneumoniae or stocking antibiotics might be vital steps to limiting any new pandemic.

Another smart intervention, the University of Georgia's Dr. Tripp said, might be to give anti-inflammatory drugs to people if they are still sick five to seven days after they get the flu.

Inflammation is not only a major reason people feel so lousy when they get the flu, he said, but it sets them up for a bacterial incursion.

"If we controlled the level of pulmonary inflammation," he said, "you wouldn't have this ticking over to a bacterial infection."

Because flu symptoms can wax and wane for as long as three weeks, figuring out whether a resurgence of illness is caused by bacterial disease can be tricky, he said.

That puts a premium on rapid detection tests, said Dr. Tripp, whose group is experimenting now with a new technique that can detect viral and bacterial diseases in 30 seconds or less.

It works by aiming a laser beam at a biological sample and detecting the "molecular fingerprint" created by light reflecting from the surface of the sample.

The technology is already being used to detect pathogens in food. The Georgia group is testing it now with the Centers for Disease Control and the Department of Defense on rapid identification of human illnesses.

Because children seem particularly susceptible to the new swine flu virus, pediatricians may need to be especially alert to secondary bacterial infections in their narrower airways, Dr. Sullivan said.

And in this case, the bad habits of some doctors may actually pay off, St. Jude's Dr. McCullers said.

"We can't seem to stop them from giving antibiotics for the common cold," he said wryly, "so in this case, it may end up being a benefit."