BASICS
Plague, one of the great historical scourges of humankind, is rare in most developed countries (1)[C].
- Except for pockets in the Southwest United States, endemic plague and transmission to humans is rare.
- Plague outbreaks still occur in some less economically developed regions of the world.
- The risk of imported cases and the concern for bioterrorism (pneumonic plague) remain public health and security concerns.
DESCRIPTION
- Acute infection due to Yersinia pestis
- Sporadic, limited geographic distribution
- In the Americas, Southwestern United States and Peru report several cases annually.
- Epidemics are associated with war, famine, and natural disasters.
- Primarily a disease of rats and other small vertebrates
- Transmitted to humans by bites from infected fleas
- Occasional human transmission in those who handle infected tissues
- Can be spread human-to-human transmission through respiratory secretions
- Infected cats may transmit disease by biting, licking, or scratching human hosts.
- Y. pestis, the infective pathogen, is a potential bioweapon.
- System(s) affected: hematologic, lymphatic, immunologic, pulmonary, skin/exocrine, sepsis
- Synonym(s): black death
EPIDEMIOLOGY
Predominant sex: male = female
Incidence
- Few cases (<10) are reported annually in the United States; typically, sporadic cases in rural areas of the Southwest in the spring, summer, or fall
- The World Health Organization (WHO) reports 1,000 to 3,000 cases per year (2)[C].
- 14% mortality rate in U.S. plague cases
ETIOLOGY AND PATHOPHYSIOLOGY
The pathophysiology of plague infection (e.g., bubonic, pneumonic, pharyngeal, meningeal, or septicemic) is determined by complex host-infectious agent interactions. The clinical outcome depends on early diagnosis and specific therapeutic interventions, including supportive care and public health measures.
- Y. pestis is transmitted by the bite of a flea from an infected rodent. It is also transmitted via secondary contact with infected tissue (e.g., ingestion of contaminated meat or handling infected tissue) or through aerosol spread (pneumonic). Organisms reach regional lymph nodes and cause hemorrhagic inflammation and "bubo " formation (bubonic plague). Spread to the bloodstream and release of endotoxin causes septicemic plague; pneumonic plague
- Untreated bubonic plague may progress to secondary pneumonic plague, which can be spread by respiratory droplets.
- Pneumonic plague and the other plague syndromes, such as septicemic plague, are rare but usually fatal.
RISK FACTORS
- Exposure to rats or fleas
- Close contact with infected cat
- Close contact with pneumonic plague patient
- Hunters who skin wild animals
- Potential bioterrorism agent
- Occupational risk: field workers, animal researchers, laboratory workers (handling Y. pestis)
GENERAL PREVENTION
- Avoid contact with vectors, infected tissue, or aerosol droplets (e.g., confirmed pneumonic plague case).
- Killed vaccine is available for people at high risk to reduce risk and/or severity; tetracycline prophylaxis. Vaccine may be requested from the Centers for Disease Control and Prevention.
DIAGNOSIS
- Due to the rarity of plague in most regions of North America, a high level of clinical suspicion is required.
- The clinical presentation and exposure history are essential to an accurate diagnosis of plague.
- If plague is suspected, clinical infection control measures, laboratory precautions (appropriate level of biosafety), and public health management practices must be implemented immediately.
HISTORY
Exposure in known endemic zone " animal (rat, cat, dog) or flea contact
- Bubonic plague: characteristic bubo formation; acute onset after 2 to 8 days incubation. Fever, chills, weakness, and headache are common.
- Septicemic plague is characterized by vascular collapse and disseminated intravascular coagulation (DIC).
- Pneumonic plague patients present with fever, myalgia, headache, and weakness. This can be difficult to distinguish from other common viral illnesses. Cough, chest pain, dyspnea, hemoptysis develop as the disease progresses (often rapidly).
PHYSICAL EXAM
- Bubonic plague
- Bubo: painful, tender enlargement of regional lymph node(s) that ruptures and drains. There is often overlying edema without an apparent skin lesion. Ascending lymphangitis is often noted.
- Skin lesions: rarely pustules, vesicles in area of flea bite(s), purpura
- Septicemic plague
- Features of bubonic plague
- Occasional occurrence without bubo
- Hypotension
- Hepatosplenomegaly
- Delirium
- Seizures in children
- Shock
- Secondary pneumonic plague
- Features of bubonic and septicemic plague
- Primary pneumonic plague
- Acute onset within hours to 1 day after inhalation of infective bacteria
- Hypotension
- Shock
DIFFERENTIAL DIAGNOSIS
Other causes of fulminant bacteremia, pneumococcal sepsis, meningococcemia; other causes of acute suppurative lymphadenitis (bubo) or rapidly progressive pneumonitis
DIAGNOSTIC TESTS & INTERPRETATION
When a case of plague is clinically suspected, caregivers and other personnel (e.g., phlebotomists, laboratory staff) should be alerted and personal protective precautions implemented immediately. Attempts to isolate and characterize the Bacillus in the laboratory must be done under appropriate conditions using standard precautions.
Common laboratory findings include:
- Elevated leukocyte count, predominantly neutrophils. Low platelet count raises concern for DIC.
- Stained smears of aspirate of bubo, sputum, and peripheral blood reveal gram-negative coccobacilli with bipolar ( "safety-pin " ) appearance.
- Aspirate, blood, and sputum cultures (e.g., infusion broth, blood, and MacConkey agar) grow typical bacteria. Public health authorities should arrange definitive identification and serologic follow-up.
- Prior antibiotic exposure may alter lab results.
- Chest x-ray: patchy or confluent pulmonary consolidation in pneumonic plague
Test Interpretation
Acute lymphadenitis with inflammation dominated by neutrophils, necrosis, masses of plague bacilli, seropurulent pericarditis
TREATMENT
- Clinical treatment includes specific antimicrobial drugs and supportive care.
- Infection-control practices and public health management are also necessary.
GENERAL MEASURES
- Avoid creation of aerosol droplets.
- Meticulous universal and personal protective measures when handling secretions.
- Notify laboratory to take precautions.
- Hot, moist compresses for buboes
MEDICATION
First Line
- Aminoglycoside: gentamicin 5 mg/kg/day or streptomycin 30 mg/kg/day IM divided q12h
- If patient is stable enough for oral medication: tetracycline 25 to 50 mg/kg/day equally divided q6h for 10 days; doxycycline 100 mg twice daily
- For meningitis: IV chloramphenicol 25 mg/kg loading dose, followed by 60 mg/kg/day in divided doses q6h for 10 days
- Fluoroquinolones (e.g., levofloxacin, ciprofloxacin) and 3rd-generation cephalosporins (e.g., cefotaxime) may also be effective.
- Contraindications
- Tetracycline: contraindicated in pregnancy and patients <8 years of age
- Precautions
- Reduce aminoglycoside dose in renal impairment.
- Pregnant women and those with hearing disorders (e.g., aminoglycosides)
- Chloramphenicol associated with hematologic toxicity
Second Line
No other drugs have been demonstrated as effective or any less toxic.
ISSUES FOR REFERRAL
Plague is reportable to public health authorities.
INPATIENT CONSIDERATIONS
Bubonic and septicemic plague syndromes are not directly transmissible person-to-person. Pneumonic plague is potentially transmissible via respiratory droplet spread, and respiratory isolation is appropriate.
Admission Criteria/Initial Stabilization
- Consider admission for all patients with suspected plague, except in widespread outbreaks when community-based care of bubonic patients may be necessary for resource management.
- In an outbreak situation, public health management and interventions for control take precedence.
- For suspected pneumonic plague, patients should undergo respiratory isolation until 48 hours of initial effective therapy or until sputum test provides negative result.
- Early initiation of appropriate antimicrobial treatment and confirmatory diagnostic testing is essential for suspected cases of plague.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- CBC for hematologic toxicity of chloramphenicol
- Aminoglycoside blood levels, if indicated
- Clinical testing for antibiotic toxicity, if indicated
DIET
As tolerated during recovery
PATIENT EDUCATION
- Avoid wild animal contact in endemic plague areas.
- Reduce rat and flea population in human environment.
- During epidemics, rodent die-off may occur, increasing flea-to-human contact.
- Flea vector management is essential for epidemic plague control.
- Centers for Disease Control and Prevention: http://www.cdc.gov/plague/
- Centers for Disease Control and Prevention. Emergency Preparedness and Response: http://www.bt.cdc.gov/agent/plague/index.asp
PROGNOSIS
- Untreated plague mortality >50%; 100% in primary pneumonic plague
- Plague may be fulminant (e.g., exposure, first symptoms, and death within 1 day in primary pneumonic plague). Do not delay the treatment of suspected cases while awaiting laboratory confirmation. Initiate treatment immediately in suspected cases of primary pneumonic plague.
COMPLICATIONS
- Progression of bubonic form to septicemic and pneumonic forms
- Necrosis of bubo may require aspiration or incision and drainage.
- Pericarditis
- Acute respiratory distress syndrome
- Meningitis
- Death
REFERENCES
11 Centers for Disease Control and Prevention. Plague, resources for clinicians. http://www.cdc.gov/plague/healthcare/clinicians.html.22 International meeting on preventing and controlling plague: the old calamity has a future. Wkly Epidemiol Rec. 2006;81(28):274 " 284.
ADDITIONAL READING
- Alvarez ML, Cardineau GA. Prevention of bubonic and pneumonic plague using plant-derived vaccines. Biotechnol Adv. 2010;28(1):184 " 196.
- Feodorova VA, Sayapina LV, Corbel MJ, et al. Russian vaccines against especially dangerous bacterial pathogens. Emerg Microbes Infect. 2014;3(12):e86.
- Frean JA, Arntzen L, Capper T, et al. In vitro activities of 14 antibiotics against 100 human isolates of Yersinia pestis from a southern African plague focus. Antimicrob Agents Chemother. 1996;40(11):2646 " 2647.
- Gascuel F, Choisy M, Duplantier JM, et al. Host resistance, population structure and the long-term persistence of bubonic plague: contributions of a modelling approach in the Malagasy focus. PLoS Comput Biol. 2013;9(5):e1003039.
- Hepburn MJ, Purcell BK, Paragas J. Pathogenesis and sepsis caused by organisms potentially utilized as biologic weapons: opportunities for targeted intervention. Curr Drug Targets. 2007;8(4):519 " 532.
- Human plague: review of regional morbidity and mortality, 2004-2009. Wkly Epidemiol Rec. 2009;85(6):40 " 45.
- Prentice MB, Rahalison L. Plague. Lancet. 2007;369(9568):1196 " 1207.
- Sun W, Roland KL, Curtiss RIII. Developing live vaccines against plague. J Infect Dev Ctries. 2011;5(9):614 " 627.
CODES
ICD10
- A20.9 Plague, unspecified
- A20.0 Bubonic plague
- A20.2 Pneumonic plague
- A20.7 Septicemic plague
- A20.1 Cellulocutaneous plague
- A20.3 Plague meningitis
- A20.8 Other forms of plague
ICD9
- 020.9 Plague, unspecified
- 020.0 Bubonic plague
- 020.5 Pneumonic plague, unspecified
- 020.2 Septicemic plague
- 020.4 Secondary pneumonic plague
- 020.1 Cellulocutaneous plague
- 020.8 Other specified types of plague
- 020.3 Primary pneumonic plague
SNOMED
- Plague (disorder)
- Bubonic plague (disorder)
- Pneumonic plague (disorder)
- Septicemic plague (disorder)
- Primary pneumonic plague
- Cellulocutaneous plague
- Secondary pneumonic plague
CLINICAL PEARLS
- Bubonic plague occurs endemically in the Southwestern United States.
- Do not delay treatment in cases of suspected primary pneumonic plague awaiting laboratory confirmation.
- Alert public health authorities for suspected cases of plague (particularly pneumonic plague and any suspicion for bioterrorism).
- Routine blood cultures will detect Y. pestis. Alert laboratory personnel if plague is suspected to ensure appropriate specimen handling.
- Prior vaccination against plague does not confer complete immunity or exclude the diagnosis.