CBRNE - Plague 

The plague has caused more fear and terror than perhaps any other infectious disease in the history of humankind. It has laid claim to nearly 200 million lives and has brought about monumental changes such as the end of the Dark Ages and the advancement of clinical research in medicine.^[1]

Although still debated by historians, the plague has been responsible for at least 3 great pandemics and multiple epidemics in history. The first spread occurred from the Middle East to the Mediterranean basin during the fifth and sixth centuries AD, killing approximately 50% of the population in these areas. The second pandemic afflicted Europe between the 8th and 14th centuries, destroying nearly 40% of the population. The third pandemic started in approximately 1855 in China, and, although it has been mostly controlled, it is still ongoing.

Alexandre Yersin isolated the plague bacillus, developed an antiserum to combat the disease, and postulated its connection with fleas and rats during the epidemic of 1894. The plague bacillus was named Yersinia pestis in his memory.^[2]

Pandemics have succeeded in entrenching the plague in every major continent, with the possible exception of Australia. Unlike smallpox, the plague never will be eradicated. It lives in millions of animals and on billions of fleas that reside on them. It is a disease of the desert, the steppes, the mountains, and the forest.^[3]

Although, the plague has been considered a disease of the Middle Ages, multiple outbreaks in India and Africa during the last 20 years have stoked fears of another global pandemic.^{[4, 5, 2]} One reason may be the climatic change brought about by global warming. This change is ideal for increasing the prevalence of Ypestis in the host population. A recent study has estimated a more than 50% increase in the plague host prevalence with an increase of 1 degree Centigrade of the temperature in spring.^[6] Another reason may be the increasing population explosion worldwide, which is bringing humans into ever-increasing contact with wildlife. Lastly, the dramatic population increase will contribute to conditions of overcrowding and poor sanitation—conditions ripe for plague hosts and vectors to flourish in.

Additionally, there has been significant concern over the return of plague as a potential biological weapon. In 1347, the Tartars catapulted bodies of plague victims over the city walls during the siege of Kaffa, and, in World War II, the Japanese dropped bombs containing fleas inoculated with Yersinia pestis to infect their enemies with the deadly illness. During the Cold War, the Soviets succeeded in aerosolizing the bacteria and in creating strains of multidrug-resistant Yersinia.^{[7, 8]} Aerosolized Y pestis, causing primary pneumonic plague, has been recognized by bioterrorism experts as having one of the highest potentials as a bioterrorism agent due to its extremely high mortality, its high uptake into enzootic and epizootic animals as well as humans, and its ability to be spread over a large area. It has been classified as a Category A select agent by the CDC.^[1]

The etiologic agent of the plague is Y pestis, a facultative anaerobic, intracellular, gram-negative bacillus. Significant genomic similarity and conservation of DNA sequences suggest Y pestis evolved from the less virulent Yersinia pseudotuberculosis.^[9]

The organism can be transmitted from a host to a human via the bite of a vector (usually a flea), via close contact with infected tissue or body fluids, and via direct inhalation of aerosolized bacteria. Currently, the most common form of transmission involves the bite of an infected flea. More than 200 different rodents and species can serve as hosts.

The vector is usually the rat flea, Xenopsylla cheopis. Thirty different flea species have been identified as able to carry the plague bacillus. Other carriers of plague include ticks and human lice. A flea is shown in the image below.

Rodents resistant to the infection, such as wood rats, kangaroo roots, deer mice, grasshopper mice, and voles, form an enzootic stage that ensures the long-term survival of the bacillus. Occasionally, fleas transfer the bacteria to animals that are susceptible to plague such as ground squirrels (an infected squirrel is shown in the image below), prairie dogs, and chipmunks. In the event of large numbers of host animals dying off, hungry fleas search out new food sources. This is known as an epizootic stage and ensures the spread of the organism to new territory. A sylvatic stage occurs when humans are infected from wild animals. Carnivores with the exception of cats and black-footed ferrets have a fairly strong resistance profile, but they can be transfer vectors. Birds and hoofed animals are seldom infected, and reptiles and fish are resistant to plague.^[3]

Virulent plague bacteria can survive dormant in soil, animal carcasses, grains, flea feces, buried bodies, and dried sputum.^{[10, 3]}

Three forms of the plague exist: bubonic plague, pneumonic plague, and septicemic plague. The bubonic form makes up approximately 80-95% of cases worldwide^[2] and is caused by deposition of the bacillus in the skin by the bite of an infected vector. If the vector is a flea, bacillus proliferates in the flea's esophagus, preventing food entry into the stomach. To overcome starvation, the flea begins a blood-sucking rampage. Between its attempts to swallow, the distended bacillus-packed esophagus recoils, depositing the bacillus into the victim's skin.

The bacillus invades nearby lymphoid tissue, producing the famous bubo, an inflamed, necrotic, and hemorrhagic lymph node. Spread occurs along the lymphatic channels toward the thoracic duct, with eventual seeding of the vasculature. Bacteremia and septicemia ensue. The bacillus potentially seeds every organ, including the lungs, liver, spleen, kidneys, and rarely even the meninges.

The most virulent form, pneumonic plague, results from direct inhalation of the bacillus, which occurs from close contact of infected hosts or from aerosolized bacteria such as may occur if used as a biological weapon. A severe and rapidly progressive multilobar bronchopneumonia ensues with subsequent bacteremia and septicemia. Secondary pneumonic plague is caused when an infected patient seeds his or her lungs and airways.

The third type of plague is a primary septicemic plague. This is hypothesized to occur when the bacillus is deposited in the vasculature, bypassing the lymphatics. Early dissemination with sepsis occurs but without the formation of a bubo. This usually is observed in bites to the oral, tonsillar, and pharyngeal area and is believed to occur because of the vascularity of the tissue and short lymphatic distance to the thoracic duct.

Frequency

United States

An average of 10-15 cases per year have been reported during the last few decades. One of the largest animal foci of the plague worldwide is found west of the 100th parallel, in states such as New Mexico, Arizona, Colorado, Utah, and California. Only one case of imported plague has been reported since 1926. Most cases occur during the wet, warmer months of the year.^[11] In 2006, 13 human plague cases were reported in the United States, the most since 1994.

International

From 1987-2001, the World Health Organization has reported an annual average of 38,876 cases of the plague with 2847 deaths worldwide. The number of actual cases is probably much higher, given the failure of many countries to diagnose and report the plague. Most cases occur in the developing countries of Africa and Asia. Recent outbreaks of the plague have occurred in Vietnam, India, Algeria, Madagascar, and the northeastern part of the Democratic Republic of the Congo.^[12] During 2000-2001, 95% of the world's cases occurred in Africa.^[2]

The illustration below shows the distribution of the plague in 1998.

Mortality/Morbidity

• Bubonic plague has a 1-15% mortality rate in treated cases and a 40-60% mortality rate in untreated cases.
• Septicemic plague (primary or secondary) has a 40% mortality rate in treated cases and 100% mortality rate in untreated cases.
• Pneumonic plague (primary or secondary) has 100% mortality rate if not treated within the first 24 hours of infection.

Sex

More than 50% of cases of plague occur in males.

Age

Approximately 50% of cases occur in persons younger than 20 years.