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The Plague: Critical Biological
Agents As Potential Weapons

A limited number of agents, if used as weapons, could cause disease and death in sufficient numbers to cripple a city or region. These agents also comprise the top of the list of "Critical Biological Agents" developed by the Centers for Disease Control and Prevention (CDC).

Yersinia pestis, the causative agent of plague, is one of the most serious of these. Given the availability of Y pestis around the world, capacity for its mass production and aerosol dissemination, difficulty in preventing such activities, high fatality rate of pneumonic plague, and potential for secondary spread of cases during an epidemic, the potential use of plague as a biological weapon is of great concern.



History and Potential As a Bioterrorist Agent

In AD 541, the first recorded plague pandemic began in Egypt and swept across Europe with attributable population losses of between 50% and 60% in North Africa, Europe, and central and southern Asia. The second plague pandemic, also known as the black death or great pestilence, began in 1346 and eventually killed 20 to 30 million people in Europe, one third of the European population. Plague spread slowly and inexorably from village to village by infected rats and humans or more quickly from country to country by ships. The pandemic lasted more than 130 years and had major political, cultural, and religious ramifications. The third pandemic began in China in 1855, spread to all inhabited continents, and ultimately killed more than 12 million people in India and China alone. Small outbreaks of plague continue to occur throughout the world.

Advances in living conditions, public health, and antibiotic therapy make future pandemics improbable. However, plague outbreaks following use of a biological weapon are a plausible threat. In World War II, a secret branch of the Japanese army, Unit 731, is reported to have dropped plague-infected fleas over populated areas of China, thereby causing outbreaks of plague. In the ensuing years, the biological weapons programs of the United States and the Soviet Union developed techniques to aerosolize plague directly, eliminating dependence on the unpredictable flea vector. In 1970, the World Health Organization (WHO) reported that, in a worst-case scenario, if 50 kg of Y pestis were released as an aerosol over a city of 5 million, pneumonic plague could occur in as many as 150,000 persons, 36,000 of whom would be expected to die. The plague bacilli would remain viable as an aerosol for 1 hour for a distance of up to 10 km. Significant numbers of city inhabitants might attempt to flee, further spreading the disease.

While US scientists had not succeeded in making quantities of plague organisms sufficient to use as an effective weapon by the time the US offensive program was terminated in 1970, Soviet scientists were able to manufacture large quantities of the agent suitable for placing into weapons. More than 10 institutes and thousands of scientists were reported to have worked with plague in the former Soviet Union. In contrast, few scientists in the United States study this disease.

There is little published information indicating actions of autonomous groups or individuals seeking to develop plague as a weapon. However, in 1995 in Ohio, a microbiologist with suspect motives was arrested after fraudulently acquiring Y pestis by mail. New antiterrorism legislation was introduced in reaction.

Epidemiology


Human plague most commonly occurs when plague-infected fleas bite humans who then develop bubonic plague. As a prelude to human epidemics, rats frequently die in large numbers, precipitating the movement of the flea population from its natural rat reservoir to humans. Although most persons infected by this route develop bubonic plague, a small minority will develop sepsis with no bubo, a form of plague termed primary septicemic plague. Neither bubonic nor septicemic plague spreads directly from person to person. A small percentage of patients with bubonic or septicemic plague develop secondary pneumonic plague and can then spread the disease by respiratory droplet. Persons contracting the disease by this route develop primary pneumonic plague.

Plague remains an enzootic infection of rats, ground squirrels, prairie dogs, and other rodents on every populated continent except Australia. Worldwide, on average in the last 50 years, 1700 cases have been reported annually. In the United States, 390 cases of plague were reported from 1947 to 1996, 84% of which were bubonic, 13% septicemic, and 2% pneumonic. Concomitant case fatality rates were 14%, 22%, and 57%, respectively. Most US cases were in New Mexico, Arizona, Colorado, and California. Of the 15 cases following exposure to domestic cats with plague, 4 were primary pneumonic plague. In the United States, the last case of human-to-human transmission of plague occurred in Los Angeles in 1924.

Although pneumonic plague has rarely been the dominant manifestation of the disease, large outbreaks of pneumonic plague have occurred. In an outbreak in Manchuria in 1910-1911, as many as 60,000 persons developed pneumonic plague; a second large Manchurian pneumonic plague outbreak occurred in 1920-1921. As would be anticipated in the preantibiotic era, nearly 100% of these cases were reported to be fatal. Reports from the Manchurian outbreaks suggested that indoor contacts of affected patients were at higher risk than outdoor contacts and that cold temperature, increased humidity, and crowding contributed to increased spread. In northern India, there was an epidemic of pneumonic plague with 1400 deaths reported at about the same time. While epidemics of pneumonic plague of this scale have not occurred since, smaller epidemics of pneumonic plague have occurred recently. In 1997 in Madagascar, 1 patient with bubonic plague and secondary pneumonic infection transmitted pneumonic plague to 18 persons, 8 of whom died.

Plague Following Use of a Biological Weapon

The epidemiology of plague following its use as a biological weapon would differ substantially from that of naturally occurring infection. Intentional dissemination of plague would most probably occur via an aerosol of Y pestis, a mechanism that has been shown to produce disease in nonhuman primates. A pneumonic plague outbreak would result with symptoms initially resembling those of other severe respiratory illnesses. The size of the outbreak would depend on factors including the quantity of biological agent used, characteristics of the strain, environmental conditions, and methods of aerosolization. Symptoms would begin to occur 1 to 6 days following exposure, and people would die quickly following onset of symptoms. Indications that plague had been artificially disseminated would be the occurrence of cases in locations not known to have enzootic infection, in persons without known risk factors, and in the absence of prior rodent deaths.

Read full report in the Journal of the American Medical Association


Reference Source: jama.ama-assn.org
December 9, 2009
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