Plague is an acute bacterial infection caused by Yersinia pestis, the pathogen responsible for three historical pandemics including the 14th-century Black Death that killed an estimated 50 million people. It persists today as an endemic disease in rodent populations across the western United States, Madagascar, Democratic Republic of Congo, and Peru, with the WHO reporting roughly 3,000 cases and 600 deaths globally each year (2010-2020).
Plague (ICD-10: A20) is a vector-borne zoonotic infection caused by Yersinia pestis, a gram-negative non-motile coccobacillus in the Enterobacterales order. The organism is maintained in nature by flea-rodent cycles, with sylvatic reservoirs in prairie dogs, ground squirrels, chipmunks, wood rats, and gerbils. Transmission to humans typically occurs through the bite of an infected rodent flea, particularly Xenopsylla cheopis and Oropsylla montana. Three clinical forms exist: bubonic plague, with infection localized to the lymph node draining the bite site; septicemic plague, with primary bacteremia and rapid sepsis; and pneumonic plague, with either primary pulmonary inoculation or hematogenous spread from another form.
The key symptoms of Plague are: Abrupt fever, often above 39°C, with chills, headache, severe myalgia, and prostration beginning 2-6 days after a flea bite or rodent exposure., A painful, tender, firm lymph node (bubo) developing within 24 hours of fever onset, typically 1-10 cm in size and located in the groin (most common), axilla, or cervical region nearest the bite., Erythema, warmth, and edema over the skin surrounding the bubo, often with the skin so tense and painful that any movement of the affected limb is unbearable., Rapidly progressive shock with hypotension and tachycardia in septicemic plague, often without a localized bubo, developing over 2-4 days from initial fever., Sudden onset of cough productive of bloody or watery sputum, pleuritic chest pain, and dyspnea in pneumonic plague — the most dangerous form, with respiratory failure within 24-48 hours if untreated., Disseminated intravascular coagulation with petechiae, purpura, and acral gangrene of fingers, toes, and nose ('black death' appearance) in late septicemic disease., Nausea, vomiting, abdominal pain, and diarrhea in approximately 25% of patients, more prominent in septicemic disease..
Diagnosis of plague requires both clinical recognition and laboratory confirmation. The most decisive single feature is a tender bubo in a patient with fever and recent exposure to fleas or wild rodents in an endemic area. Microscopy of aspirate from the bubo, blood, or sputum showing gram-negative bipolar-staining (safety-pin) coccobacilli on Wright, Giemsa, or Wayson stain provides rapid presumptive evidence. Culture remains the gold standard; Y. pestis grows on standard blood and chocolate agar in 24-48 hours, but slow growth and atypical colony morphology can delay identification, and laboratories must be alerted because the organism is a Tier 1 select agent requiring BSL-3 handling. Real-time PCR for plasminogen activator (pla) and capsule fraction 1 (F1) genes confirms diagnosis within hours and is available through the Laboratory Response Network. F1 antigen capture by ELISA or dipstick rapid diagnostic test (used in Madagascar field outbreaks) supports presumptive diagnosis at bedside. Paired acute and convalescent serology by passive hemagglutination shows a fourfold rise diagnostic of recent infection. Differential diagnosis depends on form: bubonic plague mimics tularemia, cat-scratch disease, streptococcal lymphadenitis, and lymphogranuloma venereum; septicemic plague mimics meningococcemia and gram-negative sepsis; pneumonic plague mimics community-acquired pneumonia, tularemia, anthrax, and severe acute respiratory syndromes. Because plague kills so rapidly, empirical antibiotic therapy must be started on clinical suspicion without waiting for culture results.
With prompt antibiotic therapy started within 24 hours of symptom onset, overall plague mortality is 8-15%. Bubonic plague treated within the first day of fever has a case-fatality rate under 10%. Septicemic plague carries higher mortality (30-50%) because shock and disseminated intravascular coagulation can develop before therapy reaches steady state. Pneumonic plague is almost universally fatal if treatment is delayed beyond 24 hours of cough onset, but with early aminoglycoside or fluoroquinolone therapy mortality drops to 30-50%. The 2017 Madagascar pneumonic plague outbreak documented 9% case fatality with rapid intervention by national and WHO response teams. Patients who survive acute plague generally recover without long-term sequelae, though those with severe septicemic disease may have lasting consequences from acral gangrene, amputation, or post-sepsis syndrome. Plague meningitis as a late complication is treatable but devastating if missed; routine follow-up reduces this risk. Once recovered, patients have durable immunity to homologous strains, although reinfection has been reported.
Plague is a life-threatening, rapidly progressive disease requiring immediate infectious disease consultation and admission for parenteral antibiotic therapy. Public-health coordination is mandatory because of select-agent reporting, contact tracing, and post-exposure prophylaxis obligations. Self-treatment or outpatient management of suspected plague is not appropriate.
Find specialists →Fever and constitutional symptoms typically resolve within 3-5 days of starting effective antibiotics. Buboes shrink over 1-3 weeks; some require surgical drainage. Pneumonic disease shows clinical improvement within 48-72 hours and radiographic clearance over 4-12 weeks. Septicemic patients with shock may require intensive care for 1-2 weeks and rehabilitation for several months. Full energy and exercise tolerance generally return within 2-3 months after uncomplicated disease.
Strict bed rest during the acute febrile phase. Gradual reintroduction of activity after at least 48 hours afebrile and clinically improving. Cardiorespiratory recovery from pneumonic plague can take 2-3 months; defer strenuous exercise until imaging and pulmonary function have returned to baseline.
Suspected plague should bypass primary care for emergency department or infectious disease referral. Hospitals in endemic areas (New Mexico, Arizona, Colorado, California) maintain plague preparedness protocols. In bioterrorism scenarios, treatment is coordinated by local public health authorities under CDC consultation; individual patients should follow the regimen prescribed by that response.
Medically reviewed by AIHealz Medical Editorial Board · May 13, 2026
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