One hundred years after the deadly influenza pandemic of 1918-19, are we any better prepared for the next outbreak?

Why has the influenza virus been so difficult to conquer?

Why doesn’t the vaccine work any better?

Jeremy Brown, an emergency medicine physician who is director of the Office of Emergency Care Research at the National Institutes of Health, explores these questions and more in his new book, Influenza: The Hundred-Year Hunt to Cure the Deadliest Disease in History.

"Influenza: The Hundred-Year Hunt to Cure the Deadliest Disease in History" by Dr. Jeremy Brown; Touchstone (258 pages, $26.99). (Simon & Schuster)
"Influenza: The Hundred-Year Hunt to Cure the Deadliest Disease in History" by Dr. Jeremy Brown; Touchstone (258 pages, $26.99). (Simon & Schuster)

In it, he writes that the 1918 event was “a global health crisis that killed more people than any other illness in recorded history. What we’ve learned in the interim is enough to scare and motivate us, but maybe not enough to stop another pandemic from happening.”

We recently spoke to him about his book.

Jeremy Brown is an emergency medicine physician who is director of the Office of Emergency Care Research at the National Institutes of Health.
Jeremy Brown is an emergency medicine physician who is director of the Office of Emergency Care Research at the National Institutes of Health.
Medical science has made so many advances in recent decades. Why is the influenza virus so difficult to conquer?

The influenza virus is very different from the mumps and measles and rubella viruses. Those viruses don’t change over the course of our lifetime. But the flu virus is quite the opposite. It can change and mutate extremely quickly -- from year to year, and among different populations.

That’s one of the reasons the flu vaccine is, at best, only 50 percent effective. What you thought might be a good vaccine against one strain one year might not be a good vaccine for the same strain the next year because it mutated.

The second reason is that when the Centers for Disease Control and Prevention considers what strains to include in its vaccines, it bases the recommendations on what was circulating the year before and what has been going on in the southern hemisphere, especially Australia, in their winter. And then they make their best guess. The problem is, it’s only that, even though it’s a very educated guess. And let’s say you put three virus types into the vaccine. The problem is, there could be a fourth that you just didn’t know about because it wasn’t a player last year.

Still, there is no doubt that among high-risk populations, the vaccine offers some increased measure of protection. Young children, the elderly, pregnant women, those who are immune-compromised, and people who have chronic conditions – those are the populations who are at increased risk.

By and large, the flu doesn’t do anything to other populations other than inconvenience them. That’s the reason that in Europe and the United Kingdom, the vaccine is not recommended for otherwise healthy adults, as it is here.

What are some of the most important things we don’t know about the flu?

The most important thing we don’t know is why it can strike in such different ways in different people. I just mentioned that the young, healthy population is hardly touched, and yet there are other cases, such as the one I describe in the book, of a patient who had no risk factor but came down with influenza and almost died. Suddenly, what seems to be a mild case in one person turns into a life-threatening attack in another. We don’t know why. We don’t know why it’s so much more infectious in one population and not another.

A lot of effort has gone into trying to predict flu activity. Why is that important?

We have weather forecasts. Some people think we should have flu forecasts. The reason is to prepare. If it appears the flu is getting worse in a particular area, you might want to have another go-round effort in the community to emphasize good hygiene -- sneezing into your elbow and washing your hands frequently. You might want to revisit vaccinating the at-risk population. Hospitals generally don’t keep their beds open for people who aren’t there, but that’s another avenue.

We’re not there yet. But if you could predict the flu, especially if there were to be a severe outbreak, theoretically, you could prepare for it.

The flu affects not just public health, but also so many other areas of our society. There’s the Super Bowl effect – or an effect related to any specific major sports event – where people tend to get the flu at higher rates because people are congregating at Super Bowl parties and getting infected. There were some significant effects from the 1918 outbreak, including that people who were exposed while in utero have been shown to have higher-than-expected rates of incarceration and recidivism.

Of course, there’s the business side of flu, in which you have a need to produce a vaccine, which is costly, and many vaccine manufacturers will tell you it’s essentially a money-losing venture. And you have the pharmaceutical companies trying to encourage us to use their [antiviral] products, which may be of only marginal benefit. There is, of course, the whole lobbying side of health care, which is in and of itself a huge business. Flu is a significant player in all these.

You argue convincingly that Tamiflu and similar medications aren’t very effective. Why is it still being prescribed, and why is it being stockpiled by the government for future use, at a cost of many millions of dollars?

The best answer is that while Tamiflu is not a very good drug, it may be effective in some specific populations. So, on the basis of that, there are two reasons it’s in the public eye. The first is advertising. There was a tremendous ad campaign telling parents, especially, that the flu is a big deal, when [in low-risk populations] generally it isn’t a big deal at all. That encourages people to seek out the drug that they believe will help them. Once you get to a primary-care doctor, it takes a lot of effort for him or her to explain why the drug might not be beneficial.

The second is that public attention and media scrutiny during the 2009 outbreak highlighted the need to have something we could turn to. The idea here is, well, it may be of some benefit, so what’s the harm? This hits a good point. Yet it’s not a drug that everyone should routinely be asking for. It’s a drug that everyone in the research community agrees has a marginal effect. Perhaps there are other public-health initiatives where we could spend this money to better effect. But who is going to be the person to pull it off the strategic national stockpile? That person is going to take on a great deal of responsibility. So I don’t think it’s likely to change any time soon.

We need really good clinical trials to answer the question definitively about how effective these drugs are. Armed with that information, we can see whether our stockpiling makes the best sense. Those would be expensive trials to run. But they would be a fraction of the cost of buying and maintaining antiviral drugs that may not work.

Are we prepared for the next flu pandemic?

There’s no doubt that, compared to the 1918 outbreak, we are in a far better position. We have antibiotics that will cure secondary infections. We have intensive-care units. We know how the virus spreads. So in terms of preparation, are we ready? In one aspect, certainly. But the question is, do we have the capacity in hospitals to absorb these patients? The answer there is that we don’t know.

The reason influenza is called the deadliest disease in history is that the 1918 pandemic killed 50 million to 100 million people worldwide, and about 675,000 in the U.S. In today’s numbers, that would be about 3.2 million deaths in the U.S. When you add all that up, plus the thousands of people that we suspect die as a result of complications every year worldwide, it certainly is the deadliest disease in history. This is the paradox. For so many, it is just a nuisance. Yet because it is so ubiquitous and so many people come down with it, even a small rate of complications could wind up with a significant number of people dying.