By David N. Leff

The common rat (genus Rattus) is said to be so prescient that it will jump ship when it senses that its floating habitat is about to sink. If that rodent is infected with bubonic plague, its foresighted departure does no favor to the human passengers it leaves behind. Their odds of acquiring the infection go up, not down.

This counterintuitive statement has a simple explanation: As that rat goes over the side, the dozen or so rat fleas (Xenopsylla cheopsis) that have been battening on its blood hop off their furry meal ticket and seek out the next-best warm-blooded mammal - Homo sapiens. A single bite from one plague-infected flea can deliver up to 24,000 copies of Yersinia pestis, the bacillus that inflicts plague. (See BioWorld Today, July 19, 1996, p. 1.)

This scenario carries a touch of historical irony. The Swiss scientist Alexandre Yersin (1863-1943), after whom that pathogen is named, discovered the hitherto-undemonstrated rodent connection during an outbreak of the Black Death in Hong Kong in 1894. "One of the most prophylactic measures," Yersin propounded, "would be extermination of rats."

That ex cathedra dictum gets stood on its head in today's Nature, dated Oct. 19, 2000. The lead author of the relevant paper - titled cryptically, "Metapopulation of bubonic plague" - is epidemiologist Matt Keeling, a postdoctoral research fellow at Britain's University of Cambridge. He pointed out to BioWorld Today that long after Yersin's century-old discovery, people had no idea that rats were to blame for the deadly disease.

"They hadn't got a clue about that," Keeling said. "Even the bubonic plague outbreak in Sydney, Australia, in 1900 caused a debate about what the infection's transmission routes were. One of the health officials recommended burning tar in the streets to try to clear the smells.

"It was only recently," Keeling recalled, "in the 1930s and '40s when a lot of the work was done, that really fine-tuned that this bacterium was transmitted by rats via fleas."

Centuries earlier in medieval Europe, during the great Black Death pandemics of the 1300s and 1600s, Christians attributed the scourge - which killed 40 percent to 60 percent of their population in England and Italy - to God's punishment for their sins, or Satan's malice.

Statistical Dissection Yields New Plague Insights

Keeling's article in Nature reports his computer modeling of plague epidemiology, which, he said, "produced three different results. One is the historical context," he began, "in how people perceive these irregular human epidemics. The disease dies out, then five or 10 years later, down the line, a new infection is brought in from external sources - a ship docking or whatever. What we've shown in our model is that persistence in the rat population, without need for fresh imports, leads to these irregular outbreaks of human disease.

"Secondly," he continued, "we looked at the contemporary situation and asked, 'Roughly how many rats would you need? What's the density of rats it would take to get an outbreak likely to trigger human cases?' We came up with a ballpark figure of 3,000 rats per square kilometer.

"Then," Keeling went on, "we examined the question of disease eradication, and what would happen if you started to cull the rats - get rid of them. Here we find, quite surprisingly, that if you wait until you start to see human cases, before instigating a culling of rats, you actually make the situation far worse. Because there's lots and lots of infected fleas around. You've removed their food source, which is the rats, and therefore, they start biting humans."

Notwithstanding, he observed, "The current advice given out by the World Health Organization and the U.S. Centers for Disease Control is for a mixture of both culling and the use of insecticidal flea control. People generally use insecticides just around human habitation," Keeling noted, "so statistical analysis gets more complicated when you start to factor in that mixture.

"I don't know of any instances," he added, "where people have exacerbated the system by using culling. It's a likely scenario that could happen. I think the natural human response to the presence of bubonic plague would be all-out culling of rats. But it's insecticides that you really need to stop the transmission by fleas. They would probably prevent further epidemics happening - if your rat numbers are brought very low."

Bubonic plague and its far more contagious and lethal variant, pneumonic [pulmonary] plague, are treated - successfully as a rule - with antibiotics, mainly streptomycin or tetracyclin. Three years ago public health workers discovered in Madagascar a strain of Yersinia pestis that had evolved drug resistance to antibiotics. This fell tiding, Keeling's paper warned, "is causing the bacillus to re-emerge as a significant health concern."

Although his computation model can't yet predict future outbreaks of bubonic plague, "What we can say is where there's high risk and where there's low risk. Based on our computation, high risk is anywhere that's got lots of rats that haven't seen the disease recently. Virtually all modern cities are potentially at risk because they've all got large rat populations. For example, if you think about somewhere like the U.S., we know the disease is present. There are lots of rural rodent populations, such as ground squirrels and prairie dogs. But you've then got to work out the probability of them actually getting into the towns and cities, which is a very complicated computer-modeling task."

Bubonic Plague Massacres Rats, Too

"Our model," he explained, "classifies rats into three different sorts: susceptible rats, which are likely to catch the disease; infectious rats, which will spread it onto the fleas; and resistant rats, which have had the infection, and only a small proportion survived.

"The whole model is made stochastic," Keeling continued, "meaning that every single event that happened - for example, a rat gets infected, a rat being born, a rat dying, transmission by a flea - that's all modeled as a random process. So we throw the dice, work out the probability, and see whether or not it happened.

"Rats bitten by infected fleas usually die," he observed, "with 95 to 98 percent mortality. However, there's a small fraction that survives the disease and is then resistant to Y. pestis. Their offspring can inherit the resistance from them. In Bombay, India, about 70 percent of the rats are resistant. So about 30 percent of the population could actually catch the disease."

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