Plague

Background and potential as a bioweapon

The bacteria that cause plague, Yersinia pestis, maintain their existence in a cycle involving rodents and their fleas. Plague occurs in rural and semi-rural areas of the western United States, primarily in semi-arid upland forests and grasslands where many types of rodent species can be involved. Many types of animals, such as rock squirrels, wood rats, ground squirrels, prairie dogs, chipmunks, mice, voles, and rabbits can be affected by plague. Wild carnivores can become infected by eating other infected animals.

Until World War II, the plague was a naturally occurring disease. The Chinese were the first to experience plague as a biological weapon. In WWII, a Japanese secret project bred human fleas infected them with the plague, and unleashed them on the civilian Chinese population in a number of major metropolitan areas. Thousands died, and panic resulted just as was intended. Since then, improvements in the dissemination of plague have been studied by several countries, including the USA. In 1972 the USA signed the Biological Weapons Convention, vowing never to use biological weapons.

Transmission (CDC Plague 2019)

The plague bacteria can be transmitted to humans in the following ways:

Flea bites

Plague bacteria are most often transmitted by the bite of an infected flea. During plague epizootics, many rodents die, causing hungry fleas to seek other sources of blood. People and animals that visit places where rodents have recently died from plague are at risk of being infected from flea bites. Dogs and cats may also bring plague-infected fleas into the home. Flea bite exposure may result in primary bubonic plague or septicemic plague.

Contact with contaminated fluid or tissue

Humans can become infected when handling tissue or body fluids of a plague-infected animal. For example, a hunter skinning a rabbit or other infected animal without using proper precautions could become infected with plague bacteria. This form of exposure most commonly results in bubonic plague or septicemic plague.

Infectious droplets

When a person has plague pneumonia, they may cough droplets containing the plague bacteria into air. If these bacteria-containing droplets are breathed in by another person they can cause pneumonic plague. Typically this requires direct and close contact with the person with pneumonic plague. Transmission of these droplets is the only way that plague can spread between people. This type of spread has not been documented in the United States since 1924, but still occurs with some frequency in developing countries.

Cats are particularly susceptible to plague, and can be infected by eating infected rodents. Sick cats pose a risk of transmitting infectious plague droplets to their owners or to veterinarians. Several cases of human plague have occurred in the United States in recent decades as a result of contact with infected cats.

Bioterrorism

Aerosolization of the plague bacteria has been found to be the most effective means of delivery. Aerosolization can cause large numbers of casualties from pulmonary disease several days after dispersal. The natural lag time between dispersal and symptoms of the disease make it an attractive terrorist weapon. Optimum circumstances for dispersal include:

• dense population
• cover of night
• cool, humid, still air.
  

Epidemiology

The plague is an infectious disease of animals and humans caused by the bacterium Yersinia pestis. The primary reservoir may be soil, where it can persist for years. Burrowing animals may be the first link in the chain of transmission to humans. Humans usually contract plague by being bitten by an infected rodent flea or by handling an infected animal. Droplet transmission and intentional aerosol are additional routes. Yersinia pestis is easily destroyed by sunlight and drying. However, when released into the air, the bacterium can survive for up to one hour, depending on weather conditions.

There are 4 primary forms of plague: bubonic, pharyngeal, pneumonic, and septicemic.

• Bubonic plague results when Yersinia pestis enters through a break in the skin, e.g., infected flea bites, infected animal bites or scratches, infectious material contact with non-intact skin. Bubonic plague does not spread from person to person.
• Pharyngeal plague is rare but has been documented in persons who have consumed both cooked and raw contaminated camel meat.
• Pneumonic plague occurs when the plague bacterium infects the lungs. This type of plague can spread via an airborne route from animal to person, person to person. Studies indicate that droplet transmission does not usually occur over distances beyond 3.7 feet. However, Yersinia pestis can be intentionally aerosolized, as in a terrorist attack. Untreated pneumonic plague is rapidly fatal. Pneumonic plague may also occur if a person with other forms of plague is not treated and the bacteria spread to the lungs.
• Septicemic plague: The incubation period of septicemic plague is poorly defined but likely occurs within days of exposure. Patients develop fever, chills, extreme weakness, abdominal pain, shock, and possibly bleeding into the skin and other organs. Skin and other tissues may turn black and die, especially on fingers, toes, and the nose. Septicemic plague can occur as the first symptom of plague or may develop from untreated bubonic plague. This form results from bites of infected fleas or from handling an infected animal.

Over 80% of United States plague cases have been the bubonic form. In recent decades, an average of seven human plague cases have been reported each year (range: 1–17 cases per year). Plague has occurred in people of all ages (infants up to age 96), though 50% of cases occur in people ages 12–45. It occurs in both men and women, though historically is slightly more common among men, probably because of increased outdoor activities that put them at higher risk.

INSTANT FEEDBACK:

Clinical course

Plague is caused by the gram-negative bacterium Yersinia pestis. Symptoms are either severe pneumonia or large, tender lymphadenopathy with high fever, often progressing to septicemia. Diagnosis is epidemiologic and clinical, confirmed by culture and serologic testing.  Patients with bubonic plague develop fever, headache, chills, weakness, and swollen tender lymph glands, known as buboes. Buboes are very painful, usually swollen, and often hot-to-the touch. Buboes and a history of exposure to rodents, rodent fleas, wild rabbits, or sick or dead carnivores should lead to suspicion of plague.

• Bubonic plague symptom onset is usually 2 to 6 days after a person is exposed.  Occasionally, buboes cannot be detected for a day or so after the onset of other symptoms. The disease progresses rapidly, and the bacteria can invade the bloodstream, producing a severe illness called plague septicemia.
• Once a human is infected, a progressive and potentially fatal illness generally results unless specific antibiotic therapy is given. Progression leads to blood infection and, finally, to lung infection. The infection of the lung is termed plague pneumonia, and it can be transmitted to others through the expulsion of infective respiratory droplets by coughing.

While bubonic plague is the most common form of the disease in nature, bioterrorists could aerosolize the bacteria to cause pneumonic plague. The incubation period is 1 to 4 days. The first signs of pneumonic plague are fever, headache, weakness, and rapidly developing pneumonia with shortness of breath, cough, hemoptysis, and chest pain. Pneumonia progresses for 2 to 4 days and may produce respiratory failure and shock. Without early treatment within (24 hours), patients will die. Pneumonic plague is virtually 100% fatal without early antibiosis.

Septicemic plague symptoms include fever, chills, prostration, abdominal pain, shock, petechia, disseminated intravascular coagulation and gangrene. Patients with septicemic plague do not develop the buboes that characterize bubonic plague.

Disease Management

Antibiotics used as traditional treatment options (e.g., streptomycin, tetracycline, chloramphenicol) were less active than ceftriaxone, ciprofloxacin, ofloxacin, and ampicillin, against known variants of Yersinia pestis. Antibiotics must be started ASAP. To prevent death from pneumonic plague they must be started within 24 hours of the first symptoms.

Pneumonic plague is highly contagious. Both standard and droplet precautions should be used. Antibiotic therapy for seven days will likely protect care givers and families who have direct contact with infected patients. Overall, the death rate for persons treated for the primary pneumonic plague was high despite the sensitivity of Y. pestis to aminoglycosides, quinolones, and tetracyclines and the relatively good penetration of some of these antimicrobial drugs into the lungs ( Salam, et al. 2020)

In the event of mass exposure, patients should be organized by cohort for isolation and treatment. Patient transport and isolation precautions should be as for TB. A plague vaccine is not currently available for use in the U.S.

Lastly, following an aerosol attack, the disease could persist in locales for long periods by taking residence in the soil and domestic and wild animal populations. Extermination activities may be needed to control vector and disease reservoirs.

A licensed Yersinia pestis vaccine does exist and was available in the U.S. until 1999 when the sole manufacturer discontinued production. Other vaccines are available outside the U.S. and research continues on new forms.

Click here for CDC 2021 Recommendation for Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response; Treatment tables.

Public Health

Plague is a reportable disease. According to disease-reporting rules within each state or local jurisdiction, suspected or confirmed cases must be reported to public health authorities as soon as possible.

INSTANT FEEDBACK:

References

CDC. Plague. Ecology & Transmission (2021). Retrieved 9/6/2022 from https://www.cdc.gov/plague/symptoms/index.html

CDC. Plague. Ecology & Transmission (2019) Retrieved 9/6/2022 from https://www.cdc.gov/plague/transmission/index.html

CDC. Plague. Maps and Statistics Plaque in the United States. https://www.cdc.gov/plague/maps/index.html

Nelson CA, Meaney-Delman D, Fleck-Derderian S, Cooley KM, Yu PA, Mead PS. Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response. MMWR Recomm Rep 2021;70(No. RR-3):1–27. DOI: http://dx.doi.org/10.15585/mmwr.rr7003a1

Salam, A. P., Rojek, A., Cai, E., Raberahona, M., & Horby, P. (2020). Deaths Associated with Pneumonic Plague, 1946-2017. Emerging infectious diseases, 26(10), 2432–2434. https://doi.org/10.3201/eid2610.191270

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