Laboratory Studies
The possibility of plague should be strongly considered in febrile patients from endemic areas who have history of exposure to rodents. Rapid recognition of the classic symptoms of this disease and laboratory confirmation are essential to instituting lifesaving therapy.
Expertise in testing for plague bacilli is limited to reference laboratories in plague-endemic states and the CDC.
Leukocytosis with a predominance of neutrophils is observed, and the degree of leukocytosis is proportional to the severity of illness.
Peripheral blood smear shows toxic granulations and Dӧhle bodies.
Thrombocytopenia is common, and fibrin degradation product levels may be elevated.
Serum transaminases and bilirubin levels may be elevated.
Proteinuria may be present, and abnormalities in renal function have been associated.
Hypoglycemia may be observed.
Twenty-seven percent to 96% of blood cultures are positive for Y pestis in patients with bubonic plague and septicemic plague. [26] Microbiology staff should be informed of the possibility of Y pestis agents in samples so that they can take adequate precautions when handling specimens.
Y pestis may be observed on a peripheral blood smear. Smear stained with Wright-Giemsa reveals rod-shaped bacteria. A Wayson stain demonstrates the typical "safety pin" appearance (bipolar staining) of the bacterium. Gram stain shows small gram-negative coccobacilli.
Wayson stain showing the characteristic "safety pin" appearance of Yersinia pestis, the plague bacillus. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
Lymph node aspirates often demonstrate Y pestis. In patients with pharyngeal plague, Y pestis is cultured from throat swabs.
Cerebrospinal fluid (CSF) analysis in meningeal plague may show pleocytosis with a predominance of polymorphonuclear leukocytes. [29] Gram stain of CSF may show plague bacilli.
Gram stain of sputum often reveals Y pestis.
Updated (2014) guidelines on the diagnosis and treatment of bubonic plague have been published by the Infectious Diseases Society of America (IDSA) (see Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America). [30]
Imaging Studies
Chest radiography reveals patchy infiltrates, consolidation, or a persistent cavity in patients with pneumonic plague.
ECG reveals sinus tachycardia and ST-T changes.
Nuclear imaging may help localize areas of lymphadenitis and meningeal inflammation.
Other Tests
Direct immunofluorescence testing of fluid or cultures may aid in rapid diagnosis. A novel rapid diagnostic test capable of detecting miniscule amounts of Y pestis F1 antigen within 15 minutes has been developed and field tested in Madagascar. [31] This test yields 100% sensitivity and specificity for Y pestis and other Yersinia species.
A passive hemagglutination test (performed on serum from a patient in acute or convalescent stages) with a 16-fold or greater increase in titer (single titer) suggests plague infection. [24]
A 4-fold rise in antibody titers to the F-1 antigen of Y pestis also confirms infection. [21]
A polymerase chain reaction (PCR) using primers derived from Y pestis plasminogen activator gene has been used to detect the pathogen in fleas, but the application of this method in humans is still a matter of speculation. [32]
Procedures
Aspiration of lymph node (bubo)
Inject 1 mL of sterile saline into the bubo with a 20-gauge needle; after withdrawing several times, aspirate the fluid. Gram stain of the aspirate reveals gram-negative coccobacilli and polymorphonuclear leucocytes.
Wayson stain (basic fuchsin-methylene blue, ethyl alcohol-phenol stain) of the aspirate shows plague bacilli as light-blue bacilli with dark-blue polar bodies.
Examination of the aspirate of the fluid from the inguinal lymph nodes shows a characteristic bipolar appearance that resembles a closed safety pin.
Lumbar puncture
Lumbar puncture is strongly recommended when meningeal plague is suspected.
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1998 world distribution of plague. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, GA.
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The prairie dog is a burrowing rodent of the genus Cynomys. It can harbor fleas infected with Yersinia pestis, the plague bacillus. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Oriental rat flea (Xenopsylla cheopis), the primary vector of plague, engorged with blood. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Ulcerated flea bite caused by Yersinia pestis bacteria. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Swollen lymph glands, termed buboes, are a hallmark finding in bubonic plague. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Wayson stain showing the characteristic "safety pin" appearance of Yersinia pestis, the plague bacillus. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Fluorescence antibody positivity is observed as bright, intense green staining around the cell wall of Yersinia pestis, the plague bacillus. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Histopathology of lung in fatal human plague–fibrinopurulent pneumonia. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Histopathology of lung showing pneumonia with many Yersinia pestis organisms (the plague bacillus) on a Giemsa stain. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Histopathology of spleen in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Histopathology of lymph node showing medullary necrosis and Yersinia pestis, the plague bacillus. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Histopathology of liver in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Focal hemorrhages in islet of Langerhans in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Pictured is a flea with a blocked proventriculus, which is equivalent to the gastroesophageal region in a human. In nature, this flea would develop a ravenous hunger because of its inability to digest the fibrinoid mass of blood and bacteria. If this flea were to bite a mammal, the proventriculus would be cleared, and thousands of bacteria would be regurgitated into the bite wound. Courtesy of the United States Army Environmental Hygiene Agency.
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After the femoral lymph nodes, the next most commonly involved regions in plague are the inguinal, axillary, and cervical areas. This child has an erythematous, eroded, crusting, necrotic ulcer at the presumed primary inoculation site in the left upper quadrant. This type of lesion is uncommon in patients with plague. The location of the bubo is primarily a function of the region of the body in which an infected flea inoculates plague bacilli. Courtesy of Jack Poland, PhD, Centers for Disease Control and Prevention (CDC), Fort Collins, Colo.
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Ecchymoses at the base of the neck in a girl with plague. The bandage is over the site of a prior bubo aspirate. These lesions are probably the source of the line from the children's nursery rhyme, "ring around the rosy." Courtesy of Jack Poland, PhD, Centers for Disease Control and Prevention (CDC), Fort Collins, Colo.
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Acral necrosis of the nose, the lips, and the fingers and residual ecchymoses over both forearms in a patient recovering from bubonic plague that disseminated to the blood and the lungs. At one time, the patient's entire body was ecchymotic. Reprinted from Textbook of Military Medicine. Washington, DC, US Department of the Army, Office of the Surgeon General, and Borden Institute. 1997:493. Government publication, no copyright on photos.
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Acral necrosis of the toes and residual ecchymoses over both forearms in a patient recovering from bubonic plague that disseminated to the blood and the lungs. At one time, the patient's entire body was ecchymotic. Reprinted from Textbook of Military Medicine. Washington, DC: US Department of the Army, Office of the Surgeon General, and Borden Institute. 1997:493. Government publication, no copyright on photos.
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Rock squirrel in extremis coughing blood-streaked sputum related to pneumonic plague. Courtesy of Ken Gage, PhD, Centers for Disease Control and Prevention (CDC), Fort Collins, Colo.
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CDC, Reported Cases of Human Plague - United States, 1970-2018. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, GA.
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CDC, Reported Plague Cases by Country, 2013-2018. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, GA.
