Plague: What Healthcare Professionals Need to Know 

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What is Plague?  

Plague is a serious bacterial infection caused by Yersinia pestis. There are five forms of plague: bubonic, pneumonic, septicemic, meningeal and pharyngeal.  

Plague occurs primarily in semi-arid forests and grasslands and most commonly affects animals such as squirrels, voles, rabbits, and prairie dogs. Carnivores can also be infected if they consume infected prey. Domestic animals, particularly cats, are also at risk of contracting Y. pestis in regions where plague is endemic.  

Plague is also classified as a Category A bioterrorism agent because it can cause high mortality rates when untreated, has the potential for person-to-person transmission in certain forms, and requires specialized public health preparedness. A diagnosis of plague outside of an endemic area, or an unusual increase in cases, would be concerning and would warrant an investigation to determine whether the cases resulted from natural transmission or a deliberate release of the bacterium as a biological weapon.  

How Do Humans Become Infected with Plague?  

The bacteria that cause plague, Y. pestis, can be transmitted to humans through the bites of fleas that have fed on infected animals, through handling infected animals, or through inhalation of respiratory droplets from an infected person or animal.  

An average of seven human plague cases are reported each year in the United States, primarily in northern New Mexico, northern Arizona, southern Colorado, California, southern Oregon, and western Nevada. (CDC, https://www.cdc.gov/plague/maps-statistics/index.html, Accessed 10/5/2026)  

Globally, plague occurs most frequently in Africa, although cases and outbreaks have also been reported in parts of South America and Asia. (WHO, https://www.who.int/multi-media/details/global-distribution-of-natural-plague accessed 10/6/26) From 2019–2025, most cases reported to the World Health Organization occurred in the Democratic Republic of the Congo and Madagascar. (WHO, https://www.who.int/news-room/fact-sheets/detail/plague, accessed 10/6/26) 

Pneumonic plague is the only form of plague that can be transmitted directly from person to person. Transmission generally requires close, sustained contact with an infected individual. (CDC, https://www.cdc.gov/plague/causes/index.html, Accessed 10/5/2026)  

Is Plague Deadly?  

In the Middle Ages, plague devastated communities in Europe, killing an estimated 50 million people, or 60 percent of Europe’s population at the time. Today, however, there are fewer than 5,000 cases of plague reported each, and the United States has averaged just 7 cases of plague annually in recent decades.  

Before the development of effective antibiotic treatment, the mortality from plague ranged from 66 to 93 percent. Today, antibiotics are effective against plague when treatment is started promptly; however, the disease can still be fatal if it is not recognized and treated promptly.  

How Is Plague Diagnosed 

Healthcare providers should consider a diagnosis of plague in patients who have symptoms consistent with the disease and who live, or have recently traveled to, the western United States or other regions where plague is endemic.   

The signs and symptoms of plague vary depending on the form of the disease. Of the five recognized disease forms, bubonic, pneumonic, and septicemic plague are the most common.   

Type	Risk Factors	Characteristics
Bubonic plague (most common)	Bite from infected fleas, most commonly the Oriental rat flea (Xenopsylla cheopsis)	Swollen, tender lymph nodes (i.e. “bubo”) near the site of a flea bite   Fever, chills, malaise, headache   Symptoms onset 2-8 days after exposure
Pneumonic plague	Inhaled through infectious respiratory droplets from a sick animal or human	Fever, shortness of breath, cough with purulent or bloody sputum   Chest X-ray (CXR) often looks “worse” than the patient early on in course   Bilateral pulmonary infiltrates often present   Symptoms onset 1-3 days after exposure
Septicemic plague		Occurs when the infection spreads into the bloodstream. Fever and sepsis without localizing symptoms. Abdominal pain, nausea, vomiting, or diarrhea may be present   Shock, and/or bleeding into the skin and other organs may occur, leading necrosis of the affected tissues. Delays in diagnosis are often present
Meningeal plague	Recent infection with bubonic, pneumonic, or septicemic plague	fever, stiff neck, and confusion   Present in 6% of individuals with plague.    Symptom onset 9-14 days after onset of acute plague infection
Pharyngeal plague	Contamination of the oropharynx with Y. pestis-infected materials such as inadequately cooked meat of infected animals.	Sore throat with or without swollen lymph nodes in the neck

Laboratory testing of blood or samples from an affected lymph node can help confirm the diagnosis. However, if plague is suspected, treatment should be initiated promptly because delays in treatment increase the risk of severe illness and death. 

Laboratory Considerations for Yersinia pestis 

Laboratory-associated infection is an important concern because Y. pestis has a low infectious dose and laboratory manipulation can generate infectious aerosols. (Public Health Agency of Canada, https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/yersinia-pestis-material-safety-data-sheets-msds.html, accessed 10/7/26) Aerosol- or droplet-generating activities, including vortexing, centrifugation, pipetting, preparation of suspensions, and manipulation of cultures, therefore require particular caution.

Sentinel clinical laboratories should follow the Laboratory Response Network (LRN) Rule Out or Refer approach. If Y. pestis cannot be ruled out using established phenotypic and biochemical characteristics laboratories should minimize further manipulation and immediately contact the appropriate public health or LRN reference laboratory  for guidance and confirmatory testing. (Association of Public Health Laboratories [APHL], 2020, https://aphl.org/docs/default-source/technical/PHPR-2020-Biothreat-Rule-Out.pdf, accessed 10/7/26)

Suspected isolates should be handled using appropriate containment practices, with aerosol-generating procedures performed in a certified biological safety cabinet. Suspicious isolates should not proceed through routine automated identification workflows without appropriate risk assessment. Automated biochemical identification systems and MALDI-TOF mass spectrometry systems may fail to correctly identify Y. pestis  misidentify it as another organism, including Yersinia pseudotuberculosis ( (CDC, https://www.cdc.gov/plague/hcp/diagnosis-testing/index.html, accessed 10/7/26).  

Early recognition is critical to laboratory safety. When Y. pestis is suspected, stop routine manipulation, contain the organism, and promptly communicate with public health and LRN partners. 

How Is Plague Treated?  

Prompt treatment is critical to prevent complications and to reduce the risk of death. For patients with suspected or confirmed Y. pestis infection, two classes of antibiotics are recommended for the initial treatment, with at least one considered a first-line option. Clinicians should consult the CDC’s recommendations for antimicrobial treatment and prophylaxis of plague, including guidance for both naturally occurring infection and those resulting from a bioterrorism-related event. (CDC, https://www.cdc.gov/mmwr/volumes/70/rr/rr7003a1.htm?s_cid=rr7003a1_w (Tables 1-3, 5, 7, 8), accessed 10/5/26) 

Using two antibiotics may reduce the risk of ineffective treatment while the causative strain and its antibiotic susceptibility are being evaluated. Although antibiotic resistance is uncommon in naturally occurring Y. pestis strains, strains engineered for use in a bioterrorism event could exhibit substantial resistance. Once susceptibility information is available, treatment can generally be narrowed to a single effective agent.   

What Is Appropriate PPE and Infection Control for Plague? 

Y. pestis can be transmitted through larger exhaled water particles produced when an infected person coughs or sneezes. These droplets remain suspended for a short duration of time. In addition to standard precautions, droplet precautions, meaning use of a medical mask, are recommended when caring for patients with suspected or confirmed pneumonic plague.   

The risk of disease transmission is highest in the mid- to late-stages of infection, when patients may be coughing vigorously and have high levels of bacteria in their lungs. Droplet precautions may be removed once a patient has had effective antibiotics for at least 48 hours, shows clinical improvement, and has decreased sputum production.  

Is There Post-Exposure Prophylaxis Available for Plague?  

Risk assessment for exposed health care workers should be conducted in collaboration with the facility’s Infection Prevention and Control Department and the Occupational Health team.  

Antibiotics may be offered as post-exposure prophylaxis (PEP) to individuals who had close, prolonged contact with a patient with pneumonic plague while not wearing appropriate respiratory protection. Laboratory workers who handled Y. pestis specimens without proper precautions should also be considered for prophylactic antibiotics. Finally, individuals who have had contact with any infected animal may be offered antibiotic prophylaxis.  

When indicated, antibiotic prophylaxis is generally administered 7 days following exposure Healthcare practitioners should consult the CDC’s recommendations for antimicrobial treatment and prophylaxis of plague for specific guidance on PEP management. (CDC, https://www.cdc.gov/mmwr/volumes/70/rr/rr7003a1.htm?s_cid=rr7003a1_w (Table 4, 6, and 9), accessed 10/6/26).  

Learn more: Explore the NETEC Plague Exhibit in the Resource Library for additional information on plague transmission, diagnosis, treatment, infection prevention, and preparedness.