NBC Weapons: <b>November 26, 2002</b>

The Weaponization of Plague -- New Face for an Old Enemy? Plague. The word by itself is enough to conjure up images of medieval charnel houses, where dying hordes lie in agony amidst the rotting corpses of the dead. At least one political thriller a year manages to introduce it as a biological weapon (though most writers have gone over to the more media attracting Ebola virus).

Plague is not a pleasant disease. After an incubation period of 2 to 6 days, bubonic plague (the flea transmitted version) causes a sudden onset of fever and prostration associated with painful lymphadenitis in the nodal basin draining the site of the flea bite. Buboes (painful, inflammatory, and necrotic lymph nodes) may point and drain spontaneously. Less than 10 percent of patients complain of a prior flea bite. Untreated, bubonic plague can progress to septicemic plague within 2 to 6 days. Patients with septicemic plague exhibit shock, ecchymoses, and small artery thromboses resulting in digital gangrene.

Pneumonic forms of plague can occur primarily, without antecedent bubonic disease, or, secondarily, due to dissemination of bubonic disease. Pneumonic plague is airborne and does not require flea bites. Evidence in the 1990's revealed instances where human cases of pneumonic plague were acquired from domestic cats suffering from pneumonic plague.

The case-fatality rate of untreated bubonic plague is approximately 60 percent, but less than 5 percent with antibiotic therapy. The case-fatality rate for untreated septicemic and pneumonic plague approaches 100 percent.

Plague as Weapon

Because of its high mortality (approximately 200 million deaths throughout history), Ysernia pestis has been a popular subject for study as a possible biological warfare (BW) agent. In nature, mammals of at least 73 genera and some 30 species of fleas serve as reservoirs. Humans contract disease from flea bites, and less commonly from mammalian hosts or other humans via respiratory droplet transmission. Between 1980 and 1994, 18,739 cases worldwide resulted in more than 1800 deaths. The disease is not uncommon in the American southwest, particular northern Arizona and New Mexico where it is established in the prairie dog population. The worst (and last) outbreak of pneumonic plague occurred in the United States occurred in Los Angeles in 1924. Five of eight bubonic plague cases were fatal as well as 31 of 33 pneumonic plague cases.

The weaponization of plague has a long history, beginning with Mongols throwing infected bodies over the walls of the besieged city of Kaffa in 1346. During World War II, a secret branch of the Japanese army known as Unit 731 infected Chinese water supplies with cultures of Y. pestis. They also bred human fleas (Pulex irritans) and infected them with Y pestis. The fleas were then packed into bombs and dropped over populated areas of Manchuria, causing several plague outbreaks.

During the Cold War, both the US and the USSR developed techniques to aerosolize plague directly, eliminating reliance on the flea vector. By the time the US offensive program was ended in 1970, the US did not have enough plague to make an effective weapon. The USSR, however, did -- more than ten institutes and thousands of scientists worked with plague.

Plague would likely be released as an aerosol during a modern BW attack and could generate many cases of highly lethal and contagious pneumonia. The size of the resulting outbreak of pneumonic plague would depend on several factors, including quantity of biological agent used, characteristics of the strain, method of aerosolization, and environmental conditions in the location of release (wind would spread the bacteria further, and crowding and high humidity increase the rate of infection). Bubonic plague would not ensue after aerosol release, but it could occur after transmission by fleas. The possibility of rapid death combined with potential person-to-person transmission (in contrast to anthrax) makes plague an ominous BW threat.

There is little published information indicating the actions of autonomous groups or independent people seeking to develop plague as a weapon. In Ohio, in 1995, a microbiologist was arrested after fraudulently acquiring Y. pestis by mail. New anti-terrorist legislation was introduced in reaction, making it more difficult to acquire the bacteria (but probably not difficult enough.)

Prevention/Response

The currently licensed, inactivated, whole-cell vaccine prevents bubonic plague. However, animal challenge studies suggest that it does not reliably protect against primary pneumonic plague, and thus it would not be helpful in a BW context. Hence, the best defense is recognizing the epidemic once it begins.

Symptoms of intentionally disseminated plague via aerosol would initially resemble those of other severe respiratory illnesses, and would begin 1-6 days following exposure. People would die fast. The bioterrorist provenance of the plague would be evident from the unusual location of the epidemic, its sudden presence in a multitude of people, including those with no prior risk factors (such as contact with fleas), and the absence of rodent deaths prior to the human epidemic.

One of the major stumbling blocks is the absence of rapid identification tests and a high enough level of suspicion. For example, in 1992, a 31-year-old male developed symptoms of pneumonic plague on August 22, and was hospitalized for those symptoms on August 25, where he was diagnosed with pneumonia. Antibiotics were administered, but he died 24 hours after admission. After the patient died, a rapid microbiological testing device, commonly used for diagnosis in hospitals, identified the organism isolated from the patient's sputum as Y. pseudotuberculosis (the device was not programmed to recognize Y. pestis). One week postmortem, lab tests demonstrated that Y. pestis was present. At this point, public health authorities came into play.

Clearly, recognition is a problem when it comes to diagnosing and treating the plague. If it took one week to diagnose plague in a recognized danger zone such as Arizona, it would probably take even longer on the east coast, where the possibility of plague is virtually unheard of. Once recognized, plague can be dealt with and its effects kept to a minimum. -- David W. Tschanz