Scientists dig for lessons from past pandemics

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http://www.cnn.com/2009/HEALTH/04/30/swine.flu.1918.lessons/index.html

Scientists dig for lessons from past pandemics

By Caleb Hellerman

CNN Senior Medical Producer

(CNN) -- If there's a blessing in the current swine flu epidemic, it's how

benign the illness seems to be outside the central disease cluster in Mexico.

But history offers a dark warning to anyone ready to write off the 2009 H1N1

virus.

In each of the four major pandemics since 1889, a spring wave of relatively mild

illness was followed by a second wave, a few months later, of a much more

virulent disease. This was true in 1889, 1957, 1968 and in the catastrophic flu

outbreak of 1918, which sickened an estimated third of the world's population

and killed, conservatively, 50 million people.

Lone Simonson, an epidemiologist at the National Institutes of Health, who has

studied the course of prior pandemics in both the United States and her native

Denmark, says, " The good news from past pandemics, in several experiences, is

that the majority of deaths have happened not in the first wave, but later. "

Based on this, Simonson suggests there may be time to develop an effective

vaccine before a second, more virulent strain, begins to circulate.

As swine flu -- also known as the 2009 version of the H1N1 flu strain --

spreads, Simonson and other health experts are diving into the history books for

clues about how the outbreak might unfold -- and, more importantly, how it might

be contained. In fact, the official Pandemic Influenza Operation Plan, or

O-Plan, of the U.S. Centers for Disease Control and Prevention, is based in

large part on a history lesson -- research organized by pediatrician and medical

historian Dr. Markel of the University of Michigan.

A cheerful man with thick-rimmed black glasses and a professor's manner, Markel

was tapped by the CDC to study what worked and what didn't during the 1918 flu

disaster. Markel and colleagues examined 43 cities and found that so-called

nonpharmaceutical interventions -- steps such as quarantines and school closings

-- were remarkably successful in tamping down the outbreak. " They don't make the

population immune, but they buy you time, either by preventing influenza from

getting into the community or slowing down the spread, " Markel told CNN.

Markel describes a dramatic example in the mining town of Gunnison, Colorado. In

1918, town leaders built a veritable barricade, closing down the railroad

station and blocking all roads into town. Four thousand townspeople lived on

stockpiled supplies and food from hunting or fishing. For three and a half

months, while influenza raged in nearly every city in America, Gunnison saw not

a single case of flu -- not until the spring, when roads were reopened and a

handful of residents fell sick.

Nonpharmaceutical interventions, or NPIs, also proved effective in big cities

such as New York, according to Markel. In fact, the sooner cities moved to limit

public gatherings or isolate patients, the less severe their experience tended

to be -- as much as an eight- or ninefold difference in case and death rates, he

says. Based on this guidance, the CDC preparedness plan devotes dozens of pages

to potential NPIs, from voluntary isolation to reorganizing company work

schedules to reduce the density of people sitting next to each other in the

office or while riding trains and buses.

If it seems odd to base medical strategy on 90-year-old newspapers, the approach

is increasingly popular. " There's a big case for looking at history, " says

Simonson. " We call it archaeo-epidemiology. You go to libraries and places like

that, dig around, collaborate with people like Barry and try to quantify

what really worked. "

Barry is the author of " The Great Influenza, " perhaps the signature history of

the devastating 1918 pandemic. He says the historical record shows that

isolating patients worked to slow the spread of flu in 1918, but that attempted

quarantines -- preventing movement in and out of cities -- was " worthless. "

While Barry supports the CDC's general containment strategy, in the past he has

charged that Markel's findings rest on flimsy historical research. After the

findings were published in the Journal of the American Medical Association,

Barry wrote a letter in response, saying it wasn't swift action but rather an

earlier wave of mild flu, acting like a vaccination, that was probably

responsible for New York's relatively low caseload. In the letter, he noted,

" New York City health commissioner Royal Copeland did tell reporters...that he

would isolate and quarantine cases, " but based on his own articles in the New

York Medical Journal, he " apparently never imposed those measures. "

It looks superficially like an academic feud, but in this field, different

conclusions can suggest radically different approaches to quashing a pandemic.

Nowhere is this more true than in research that builds computer models to

predict the spread of outbreaks, based on previous ones. Markel, along with most

analysts, says that in prior pandemics, the so-called R-naught number -- the

number of new infections caused by each infected person -- has been

approximately 2.0. The current U.S. pandemic control strategy is based on

computer simulations that assume a flu virus with an R-naught between 1.6 and

2.4.

Last year, however, Simonson and Viggo sen concluded that the true

R-naught of the 1918 flu virus was probably somewhere between 3 and 4. Since an

epidemic grows exponentially -- each person sickens three others, each of whom

infects three more, and so on -- this is a tremendous difference. " It says it's

going to be harder than we thought " to control a pandemic, " Simonson says with

grim understatement.

Barry agrees. " I do think that some of these things, like isolating [sick

people], will take off some of the edge. We hope they'll do more than that. But

to think they'll stop a pandemic, that is just not going to happen. "

Simonson says control measures such as the steps taken by Mexico in recent days

-- closing schools and restaurants, for example -- are still worth the effort.

" It doesn't mean we should give up, because we don't know the R-naught [for

swine flu]. We don't know how easily this spreads. " But she adds, NPIs are at

best a way to buy time. " We just badly need a vaccine. That's the most important

thing. "

To date, the CDC has emphasized personal protective steps such as washing hands

and using hand gels, as opposed to tightening border controls or issuing formal

directives to close schools or limit public gatherings. Such steps have been

left to state and local officials, who have responded in a variety of ways.

One reason for the delay in stronger guidelines is that swine flu caught

planners off guard; they had anticipated being able to recognize a pandemic

overseas, weeks or at least days before it hit the United States. At the same

time, CDC acting director Dr. Besser said Thursday that it's important

to let officials tailor their response to local conditions. " They can take the

recommendations we're providing and apply them locally. [by doing that] we hope

to learn and see what are the most effective control strategies. "

Markel agrees that the best response depends on the particular situation.

" History is not predictive science. And the powers of public health officials

[in 1918] were much greater. Another difference is that people's trust of

doctors and government in 1918 was probably remarkably different.... But what I

have found, studying epidemics, is that good planning and good relationships

between local state and federal authorities, goes a long way. "