ARTICLE - PRELUDE TO A PLAGUE

PRELUDE TO A PLAGUE
(Science Now) - By Kristen Minogue

No warning. In countries that already have some immunity to cholera, a new strain could create a minor stir before a major outbreak. But in Haiti, it took the population completely by surprise.

In the summer of 1849, a mass epidemic of cholera overran the city of London, leaving more than 13,000 dead. It wasn't the first or the last to terrorize the city before the disease vanished in 1901; major epidemics occurred in 1832, 1854, and 1866. Now new evidence suggests that the 1849 epidemic, and two more of the city's worst outbreaks, may have come with a warning—a prequel that could tip off health officials to pending outbreaks today.

These prequels, called herald waves, killed hundreds, not thousands, says Joseph Tien, a mathematical biologist at Ohio State University in Columbus. His team detected three of them—each happening months before one of London's four "great" cholera years.

It was the seasons that gave them away. Tien and his colleagues looked at weekly records of cholera deaths in London stretching from 1824 to 1901, the date of the city's last recorded cholera fatality. They discovered that cholera outbreaks always struck in summer, with only three exceptions: spring of 1832, autumn of 1848, and winter of 1853. Each of these three rogue outbreaks was followed by an unusually severe epidemic the following summer.

"They kind of jumped out from the cholera data," says Tien, whose team publishes its findings online today in Royal Society Interface. The researchers speculate that an invasion of a new cholera strain could have triggered the prequels. A new bacterium could do damage to a vulnerable population not yet immune to it, but if it arrived during the off-season, climate conditions would hold it in check. That is, until the summer months, when warmer temperatures would allow it to resurface with a vengeance. A mathematical simulation confirms that idea, but the authors concede that the new strain hypothesis needs genetic or biological data to back it up.

The one potential wrench in the team's hypothesis occurred in 1866: a cholera epidemic that killed more than 5000 people and came with no apparent herald wave. The researchers suggest that it could have been a new strain that happened to arrive just as the cholera season began. But Tien acknowledges other environmental factors could also be at play.

"I'm impressed and somewhat excited about this paper," says Donald Olson, an epidemiologist at the International Society for Disease Surveillance in Boston who was not involved in the research. Olson studied a similar herald wave for the 1918 influenza epidemic in New York City—part of the great "Spanish flu" pandemic—but he says this is the first time anyone has recorded one for cholera.

Justin Lessler, an epidemiologist at Johns Hopkins University in Baltimore, Maryland, agrees that this would be a first. But Lessler says he isn't surprised that cholera epidemics could have preludes. "People who do modeling would expect this for any seasonally driven epidemic."

The biggest challenge, according to Lessler, is figuring out when cholera season occurs in various locales. In temperate climates such as London's, he says it's reasonable to expect cholera to strike in the warm summer months. But for tropical regions like Bangladesh, one of cholera's key strongholds in the 21st century, the disease can depend much more on local factors such as the timing of the rainy season. And in Haiti, where cholera has not been seen for at least a century, it's even less clear when the season would start. Because the Haitian population has virtually no immunity, cholera could be devastating no matter when it struck.

Still, for regions where researchers know the season when cholera usually occurs, Lessler says an off-season outbreak could be an invaluable warning to gear up for a more serious one in the near future. "You wouldn't want to get too happy when that off-season epidemic started waning."