When a person in northern Arizona died of the plague in July 2025, we wondered if we had time-traveled back to the medieval era. The last time most of us thought about the plague was likely in school, studying for our boards.
Now, between this fatality in Arizona and a subsequent, well-publicized case in California, front-line clinicians need to refresh our memories about the plague. How worried should we be? And are we prepared to recognize the plague in our own practice settings?
The plague is caused by Yersinia pestis, a gram-negative, non-spore-forming bacterium. It caused the infamous Black Death of the 1300s that tore through Asia and Europe, wiping out about one-third of Europe’s population along the way.
Today, we know Yersinia pestis is transmitted via three main routes:
Flea bites, especially from prairie dogs, squirrels, and rodents
Contact with infected animals, especially cats
Inhalation of droplets from people with pneumonic plague
The plague is reassuringly rare. In the United States, we average about 7 human cases of plague each year, 80% of which are the bubonic form of the disease. Currently, most domestic cases occur in the western U.S., especially Arizona, northern New Mexico, and southern Colorado. Around the world, most cases originate in Africa, Asia, and South America.
More worrisome is that the plague is rapidly lethal if not treated quickly. Even if most of us may never see a case of the plague in our careers (knock on wood), we need to suspect it in the right scenarios so that our patients can receive the higher level of care they need ASAP.
There are a few high-risk groups of people clinicians need to be familiar with, including people with a lot of outdoor exposures (think campers, hikers, and outdoor workers), people who come into regular contact with animals (like veterinarians and pet owners), and anyone with recent travel to a plague-endemic area. If we consider how the plague is transmitted – via flea bites or infected animals, for example – these groups make sense.
The plague comes in three different forms: bubonic, septicemic, and pneumonic. No matter the type, patients can present with fever and chills. Beyond that, each form of the plague has some unique identifying characteristics.
1. Bubonic plague
This is the most common form. Its hallmark consists of very painful, enlarged lymph nodes (aka buboes — the name tells you what to look for). It usually appears 2–8 days after a flea bite, due to bacterial multiplication in the affected lymph nodes.
2. Septicemic plague
This is a systemic illness with GI symptoms, multi-organ failure, and skin necrosis of the extremities in its later stages. It can result from a flea bite, direct contact with infected animals, or even untreated bubonic plague.
3. Pneumonic plague
This is a rapidly progressive pneumonia with classic symptoms of cough, dyspnea, and even hemoptysis. It is the only type of plague transmitted from human to human via respiratory droplets. If a person has untreated bubonic or septicemic plague, it can progress to pneumonic plague as well. Very importantly, it is rapidly fatal if left untreated – we’re talking within 1-2 days.
The plague is tricky because it shows up like so many other things we see every day: a febrile patient with lymphadenopathy, maybe a cough, maybe some abdominal symptoms. To suspect this diagnosis, we need a combination of the right exposure history and typical symptoms.
In our patient histories, we can ask about recent travel to the western U.S. or other endemic regions around the world, as well as any recent outdoor activities like camping or hiking. We should also look for any contact with potentially infected animals, pets with rodent exposure (such as outdoor cats), or recent flea bites.
On exam, physical signs that should raise our plague antenna include fluctuant, tender lymph nodes, signs of sepsis without a clear source, pulmonary symptoms with rapid deterioration, and skin findings of petechiae or even acral necrosis.
Realistically, most primary care and urgent care clinicians are not going to initiate an extensive lab and imaging workup. We’re going to get our patients to a higher level of care right away. In the emergency department or inpatient setting, a reasonable workup might include a CBC to look for leukocytosis and thrombocytopenia, blood and lymph node aspirate cultures, and chest imaging if the patient has respiratory symptoms.
Interestingly, rapid antigen tests for the plague do exist and are used primarily in lower-resource global settings as a public health tool. These tests are not yet FDA-approved, though, so most of us won’t ever order them.
If we have the ability and resources to initiate treatment before sending our patient to the nearest E.D., we should do so. Mortality approaches nearly 100% without treatment, but outcomes improve significantly if we can get antibiotics on board early. We can feel empowered to start antibiotics even before any confirmatory testing is done.
Oral options include levofloxacin 500 mg daily, ciprofloxacin 500 to 750 mg twice a day, and doxycycline 100 mg twice a day. The main IV option available in most practice settings is gentamicin, dosed by weight.
Our local health departments should always be kept in the loop as well, for contact tracing and community notification.
In our health care settings, droplet isolation measures should be in place as we care for these patients. And if our patients’ family members ask if they need to worry about the plague, post-exposure prophylaxis for close contacts consists of doxycycline or ciprofloxacin for 7 days.
Is plague likely to be at the top of your differential for most of your patients? Definitely not.
Should it ever be on your list? Yes, especially if your patient lives in or has traveled to an endemic area and presents with the right symptoms.
This is one of those rare-but-deadly diagnoses where clinical suspicion is everything, and where you can truly save lives if your patient gets the right care, right away.
For more on the plague, check out our full conversation on the Primary Care Reviews and Perspectives podcast and Urgent Care Reviews and Perspectives podcast episodes with Dr. Geoff Comp and Dr. Neda Frayha.