OVERVIEW: What every practitioner needs to know

Are you sure your patient has pneumonic plague? What should you expect to find?

Pneumonic plague is the most life-threatening manifestation of Yersinia pestis infection. Two clinical forms, primary, and more commonly secondary to bubonic plague.

Primary plague pneumonia is typically an alveolar process, initially lobular and rapidly spreading to multiple lobes; secondary plague pneumonia is a more diffuse but also rapidly progressing interstitial process.
Sudden onset of fever, chills, profound malaise, headache, myalgias plus cough, worsening chest discomfort and pain, dyspnea, hemoptysis and respiratory distress progressing to cardiopulmonary failure. Auscultatory findings are scant and non-specific.

How did the patient develop pneumonic plague? What was the primary source from which the infection spread?

Primary pneumonic plague most often results from inhalation of infectious respiratory droplets; secondary pneumonia is metastatic from bubonic plague, most often transmitted by flea bites or direct contact with infected (including domestic) animals.
Yersinia pestis is a zoonosis. Humans (and non-rodent mammals) are sporadic and incidental hosts. Susceptible animals include prairie dogs, rock and ground squirrels, chipmunks and wood rats and their fleas, in foci located in Africa (80% of human cases); Asia (15%) and North and South America (5%). Transmission to humans is more common in semi-rural areas in the vicinity of the patient’s homes. Pneumonic plague represents a minority of human cases. Outbreaks of primary pneumonic plague occur sporadically; respiratory spread by infective droplets has been documented. Yersinia pestiscan be used as a biological weapon.
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Which individuals are of greater risk of developing pneumonic plague?

Close contacts with patients suffering primary plague pneumonia, especially with those that produce copious sputum. Family and care givers are at highest risk. Patients with bubonic plague are at high risk for secondary plague pneumonia. Laboratory personnel are also at risk for disease.
High index of suspicion based on detailed clinical information and sound epidemiological history should be present when evaluating persons living in areas with poor sanitation that harbor large rat populations (especially black rats and relatives) plus rat fleas.

Beware: there are other diseases that can mimic pneumonic plague:

Rapidly progressive bacterial pneumonia very similar to pneumonic plague can be caused by Streptococcus pneumoniae, Staphylococcus aureus, Francisella tularensis, Legionella pneumophila and Coxiella burnetii. Similarly, severe viral pneumonia caused by influenza A and B viruses, hantavirus, and coronavirus mimic primary and secondary pneumonic plague.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

Leukocytosis, at times extreme, and left shift are common.
Gram stain of lower respiratory secretion can strongly suggest the diagnosis when typical bipolar staining of organisms is found.
Primary Plague Pneumonia: Acute, extensive lobar infiltrates progressing to bronchopneumonia and extending to opposite lung, at times associated with cavitation.
Secondary Plague Pneumonia: Severe, generalized interstitial pneumonitis.

Results that confirm the diagnosis

Blood or sputum cultures positive for Yersinia pestis are diagnostic.
When available IgM and IgG Y. pestis antibodies are useful.
Other rapid tests such as polymerase chain reaction (PCR) can aid in early confirmation of diagnosis.
Antibodies against F1 Y. pestis antigen can also be measured by passive hemagglutination. A reference laboratory should be involved from the moment of suspicion.

What imaging studies will be helpful in making or excluding the diagnosis of pneumonic plague?

Serial Chest X-Rays (CXR)
Pulmonary computed tomography (CT) scan
CXR: 60-125, CT: 125-500

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has pneumonic plague, what therapies should you initiate immediately?

Consultations: Infectious Diseases, Pulmonology, Intensive Care
Therapies: IV Gentamicin, 5mg/kg per day. Streptomycin has been the drug of choice based on clinical experience but is less commonly available. Doxycycline and chloramphenicol are alternatives or de-escalation choices (See Table I).

Table I.n

Pneumonic plague in adults

1. Anti-infective agents

If I am not sure what pathogen is causing the infection, what anti-infective should I order?

Add gentamicin at above doses to regimen used to treat severe pneumonia while firm diagnosis is established.

What complications could arise as a consequence of pneumonic plague?

Acute respiratory distress syndrome (ARDS), cardiopulmonary insufficiency, hypotension, sepsis, septic shock, organ failure, and death (including sudden death).

What should you tell the family about the patient's prognosis?

This is a very serious disease with a guarded prognosis. There is a need for immediate admission, isolation and prompt empirical or directed antimicrobial treatment. Possibility of transmission to family members via aerosols.

Most important risk factor for death is lack or delay in appropriate antimicrobial treatment. Mortality approaches 100% in untreated plague pneumonia.

How do these pathogens cause pneumonic plague?

Y. pestis is extremely virulent due to a potent lipopolysaccharide (LPS) endotoxin. After inhalation or hematogenous spread, lung infection and damage occur rapidly. Usual pathological findings include diffuse pulmonary infiltrate with necrosis, hemorrhage and mild polymorphonuclear leukocyte infiltration.

How can pneumonic plague be prevented?

For individuals living, working or participating in recreational activities in areas where plague is enzootic, these areas are frequently known and marked and should be avoided. Personal protection measures such as the use of appropriate clothing (including gloves when handling dead animals), insecticides and repellents must be encouraged. Anti Y. pestis prophylaxis is available with doxycycline, trimethoprim/sulfamethoxazole and ciprofloxacin; the latter has been recommended in bioterrorism response plans and accidental laboratory exposure.

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Pneumonic plague