Plague draws scientists' attention as potential terrorism weapon

WASHINGTON – Isaac Baniyo stumbled through his final exam in English last November as a pounding headache and chest pain made it difficult for him to focus. Within days, his fever soared, and he was hacking up bloody mucus. The dead rats in his village should have been a warning sign: Baniyo had caught pneumonic plague, the contagious form of the disease responsible for history’s most notorious epidemics, including the Black Death of the 14th century.

Baniyo lives in a small village in Uganda, but his case is of keen interest in other nations. In an era of cheap air travel and international terrorism, scientists and national security experts are concerned that, much like anthrax, plague could pose a threat as a biological weapon.

“It’s been on national lists as one of the more serious biological agents for a long time,” said Tom Ingelsby, director of the Center for Biosecurity of the University of Pittsburgh Medical Center. Plague bacteria lack the hard spores that makes anthrax so durable, but because it spreads so easily and kills more than one-third of those it infects in developing countries, the Centers for Disease Control and Prevention considers it a Category A bioterrorism agent, alongside smallpox and Ebola.

Plague as a biological weapon is not new. During World War II, Japanese planes reportedly dropped plague-infected fleas over Chinese settlements, and scientists in the former Soviet Union made large quantities of plague, potentially including drug-resistant varieties, for warfare.

According to the World Health Organization, about 45 kg of aerosolized plague bacteria sprayed over a city of 5 million might sicken 150,000 people, fueling an epidemic, particularly if antibiotics were in short supply.

Such an epidemic is exactly what the CDC is trying to avert along the Uganda-Democratic Republic of Congo border, where nature, not bioterrorism, spreads the disease. According to epidemiologist Paul Mead of CDC’s division of vector-borne diseases in Fort Collins, Colorado, new diagnostic tools and drugs will not only help Africans but also will provide a bulwark in the event of an outbreak or attack in the U.S.

“We’re not going to completely eliminate plague,” Mead said, “but if we can put out the fire early on, we can reduce the deaths and economic impact.”

Plague has spread with humanity and its rats to the burrows of prairie dogs in the United States Southwest and up the Nile River to remote corners of Africa. Far from being consigned to the Middle Ages, a 1994 outbreak in India resulted in 5,150 suspected plague cases and 53 deaths, which led the CDC to evaluate sick passengers arriving in the United States from India. Today, more than 1,000 plague cases are thought to occur globally each year, with more than 95 percent of them in Africa, particularly Uganda, Congo and Madagascar.

The plague bacteria, Yersinia pestis, typically makes the leap to humans as infected rats die, forcing fleas to find a new host. The best-known form of the disease, bubonic plague, results in painful, golf ball-size swellings, known as buboes, in the lymph nodes of the groin or armpit. Plague can also cause hemorrhaging of blood vessels in the fingers and nose, leading to dark-purplish gangrene — hence the name “Black Death.” If bacteria reach the lungs, the pneumonic form of plague can spread from person to person through coughing. Untreated, plague is almost always fatal within a week, but identified within the first 24 to 48 hours, it can usually be cured with antibiotics.

Because the United States has an average of just five plague infections each year, CDC researchers decided in 2003 to conduct their research on predicting and preventing outbreaks abroad, and they focused on Uganda. In the decade since, they have identified 1,287 suspected plague cases.

The only way to definitively diagnose bubonic plague was typically to insert a hypodermic needle directly into a bubo, inject a solution and withdraw the fluid. The sample was then cultured, stained and put on a slide. Under a microscope, Yersinia pestis looks like a safety pin — an oval with caps on either end. Prior to the CDC’s involvement, most clinics in Uganda didn’t have microscopes, nor the expertise to use them, much less an adequate supply of sterile needles and solution.

But after years of testing in Uganda, the CDC is finishing a study of a low-cost dipstick, not unlike a home pregnancy test, which requires just a drop of blood or urine to reveal within minutes if a person has plague. Jeff Borchert, the CDC scientist who oversees the project in Uganda, says that having such a test will be critical in the event of a biological attack and that the United States could provide free tests to Uganda and other plague-endemic countries.

Meanwhile, the researchers have sought to expand drug options, because some intravenous antibiotics, such as streptomycin, are not widely available and because drug resistance to other antibiotics poses a concern. The go-to pill for an anthrax attack is ciprofloxacin, which is part of the U.S. Strategic National Stockpile established for national emergencies.

As part of the ongoing clinical trials, 14-year-old Isaac Baniyo’s plague was diagnosed with a dipstick; he then became the fifth plague patient — and the first with the pneumonic form of the disease — treated with a 10-day dose of cipro. Fortunately, the drug worked for him.

Despite their efforts so far in Uganda, the team has not achieved its goal of reducing plague mortality from about 30 percent to 15 percent. Mead at first suspected that people farthest from clinics were not getting diagnosis and treatment within the two-day window that makes the difference. That hunch proved wrong.

It turned out that cultural traditions were key, and they were working against the CDC. Many people in Baniyo’s village rely on traditional healers, who treat illness with herbs or prayers. During a 2008 outbreak of pneumonic plague, the healer was one of those sickened — and a fully stocked clinic was less than a kilometer away. “Having a diagnostic dipstick and effective antibiotics doesn’t really matter if a person doesn’t get to the clinic,” Mead said.

So in 2010, Titus Apangu of the Ugandan Virus Research Institute, with funding from the CDC, began recruiting 10 of these traditional healers, training them to recognize plague symptoms and providing them with bicycles, cellphones and referral cards to direct patients to a specialist at the local clinic. The number of healers working with the institute has now climbed to 42, and they have made 562 referrals for suspected cases of plague, malaria, tuberculosis and other serious illnesses. Some are even sporting homemade uniforms with a CDC logo.

On a recent morning, Mark Wadribo, a healer in a blue sweater with a wooden cross around his neck, pulled out his book of referrals and told the story of a young farmer who limped into his compound last year. The man was so weak, he could barely speak. “When I examined him, I found high fever,” Wadribo recalled. “I asked if he had swellings.” The man revealed a bubo on the left side of his groin.

In the past, Wadribo treated such patients by making incisions and rubbing herbs in the wound. This time, he grabbed his cellphone and told his brother to ready the motorbike. They had a plague to stop.