Rudolph's Pediatrics, 22nd Ed.

CHAPTER 279. Plague

Gary D. Overturf

Plague exists worldwide as continuing enzootic sylvatic disease in rodent-flea cycles that occasionally spreads into the human population. Yersinia pestis, the causative organism, is a nonmotile, gram-negative, non–spore-forming, coccobacillus.


The geographic distribution of plague is largely confined to the semiarid areas of most continents, with the exception of Australia. Enzootic North America foci are the largest in the world, occurring primarily in the southwestern United States (extending east as far as Dallas, Texas) and the Pacific coastal region, extending from Coahuila, Mexico, to Alberta and British Columbia, Canada. The disease exists almost entirely in the sylvatic form, with rodent-flea cycles among a number of wild rodent species.1 Urban plague, the cause of the epidemics of the European Middle Ages, is dependent upon the Norwegian rat and flea (Xenopsylla cheopis), but is now quite rare. The last epidemic of urban US plague occurred in 1925 in Los Angeles. Rarely, pneumonic plague is transmissible from person to person, bypassing both the rat reservoir and the flea vector.1,2

In the United States and Canada, the epidemiology is more complex and involves a number of different rodent hosts and flea vectors, as well as domestic animals. Most commonly, the infection is acquired by human exposure to infected tissues or from the bites of fleas of wild rodents such as prairie dogs, ground squirrels, chipmunks, rabbits, and other wild rodent species. Contact with squirrels accounts for nearly half of the exposures. Domestic animals, especially cats, may become infected after contact with wildlife and may transmit the infection to humans.2


In the United States, most human plague cases occur from May to September and usually present as 1 of 3 primary forms: bubonic, septicemic, or pneumonic. Bubonic plague accounts for 78% of US cases, the remainder are septicemic (13.2%), pneumonic (4.4%), and meningitic or unknown (3.4%).3

The incubation period of bubonic and septicemic plague is often difficult to determine but is usually within 2 to 6 days (range 1–10 days) of contact. Skin lesions are infrequently present at the site of initial infection (eg, flea bite). The first symptom usually consists of sudden onset of fever (39°C/102.2°F or higher), often accompanied by shaking chills. Within hours to a few days, exquisitely tender, painful, often erythematous or swollen lymph nodes are present; severe pain may occur prior to swelling. The most frequently involved nodes are the inguinal or femoral nodes, followed by axillary and cervical nodes, but any node may be involved. The nodes enlarge rapidly, forming the characteristic bubo. There may be erythema of the overlying skin. Buboes may vary in diameter from 1 to several centimeters. Patients presenting with septicemic plague fail to develop visible buboes.

Fever may be accompanied by profound malaise, severe headache, photophobia, abdominal pain, nausea, vomiting, diarrhea, restlessness, delirium, myalgias, and weakness. Fever usually peaks during the first 24 hours and then continues at slightly lower levels for 3 to 4 days, with occasional morning remissions. The temperature may then fall, sometimes achieving nearly normal levels, followed almost immediately by a second steep rise. If no complications or pulmonary disease develop, the fever again gradually declines after the seventh to tenth day of illness, often in association with spontaneous rupture of the buboes.

Frequent signs are marked tachycardia, tachypnea, and hypotension. The buboes, if present, increase in size over several days until they become fluctuant and the overlying skin hemorrhagic. With clinical recovery, the lymph node abscess clears slowly, often healing within 2 weeks after onset, although occasionally the process may become chronic, with the formation of ulcers and draining fistulas.

Bacteremia occurs regularly during the early phase of the disease in both mild and severe forms. In some instances, the reticuloendothelial system clears the bloodstream of organisms. In other individuals, these defenses are overwhelmed and a septic phase develops, during which the patient may succumb to overwhelming endotoxemia. The bacteria may spread through the blood to the respiratory system, producing secondary pneumonia with pulmonary hemorrhages, edema, abscesses, or bronchitis. In addition, other organs, such as the brain and meninges, may become infected. A disseminated intravascular coagulation syndrome leading to gangrene of the skin, appendages, and various other organs may occur in patients who survive the initial endotoxemia.

A relatively mild form of plague (pestis minor) occurs rarely and may remain unrecognized. These patients demonstrate minimal toxicity, a low-grade fever, and simple lymphadenitis rather than buboes. This clinical picture is the result of infection with a strain of Y pestis lacking one or more of the virulence factors.

Pneumonic plague is usually quickly fatal, whether it is acquired by inhaling infected aerosol (primary pneumonic plague) or is secondary to hematogenous infection from septic illness (secondary pneumonic plague). The incubation period of primary pneumonic disease is very short, often less than 24 hours. Radiologically, the process may resemble a lobar or bronchial pneumonia or a massive pulmonary edema (eg, respiratory distress syndrome). The majority of patients die within a few hours, despite appropriate therapy. The use of plague as a bioweapon is likely to be disseminated by aerosols, and thus primary pneumonic plague is likely to be the most common presentation.


The bubonic form is usually accompanied by significant leukocytosis up to 50,000/mm3, whereas in the pneumonic and septicemic forms, leukopenia or leukocytosis may be found with varying proportions of young and immature polymorphonuclear leukocytes. In meningitis, the usual spinal fluid changes of bacterial disease are present (Chapter 231).

The diagnosis is established by detecting typical gram-negative organisms in blood cultures, sputum smears, or aspirates of the affected lymph nodes (buboes). These procedures by themselves do not serve to differentiate plague from tularemia. Culture of the organism is usually successful, but often definitive species identification is carried out only in reference or public health laboratories. A positive fluorescent antibody staining test (often directed against the F1 capsular protein) permits rapid both presumptive and species-specific diagnosis.

Classic bubonic plague can be recognized readily on clinical grounds, but the signs and symptoms of the septicemic form are similar to those of other gram-negative septicemias. Tularemia, especially when tickborne, may greatly resemble plague, but the site of the initial bite is usually more evident with tularemia.


Patients with suspected plague should be placed in isolation until 48 hours after starting effective antimicrobial therapy to prevent the potential spread of infection from possible pulmonary involvement. Therapy should be initiated as soon as the diagnosis is suspected and not await definitive diagnosis. Bodily fluids, secretions, and pus should be handled with gloves. Personnel caring for patients who are coughing should wear face masks and goggles. Careful attention must be paid to waste disposal because feces often contain Y pestis.

Several antimicrobial agents are useful in specific therapy, including tetracycline, streptomycin, gentamicin, chloramphenicol, and trimethoprim-sulfamethoxazole. The efficacy of trimethoprim-sulfamethoxazole is probably similar to that of tetracycline, but there is considerable documented clinical experience with tetracycline.

Standard recommended therapy for plague is tetracycline and streptomycin. However, gentamicin is as effective as streptomycin and is probably the most appropriate drug to use. It is uncertain whether an aminoglycoside or tetracycline, or a combination of the two, is preferable.

Aminoglycosides should be given cautiously, in a dosage of 30 mg/kg per day in 3 equal doses for streptomycin, or 5 to 6 mg/kg per day for gentamicin. The patient must be carefully monitored for signs of impending shock. After 5 days, tetracycline is substituted at an oral dosage of 25 to 30 mg/kg per day, divided into 4 equal doses for at least an additional 5 days. When used as primary therapy for severe bubonic plague, the dosage of tetracycline is 40 to 50 mg/kg per day (in 4 equal doses) after a loading dose of 30 mg/kg; alternatively, doxycycline can be used in dosage of 4 mg/kg (day 1) and 2 mg/kg thereafter up to a maximum dose of 100 mg twice daily. After the first 24 to 48 hours of therapy, the dosage of tetracycline can be reduced to the lower dose. Treatment is generally continued for 1 week after body temperature returns to normal or for a total of approximately 10 days. Chloramphenicol, a less desirable choice than tetracycline, is given at a dosage of 25 to 50 mg/kg per day in four divided doses (maximum of 2 g/dose). Chloramphenicol is preferred only in the treatment of known or suspected plague meningitis or when treatment with tetracycline or aminoglycosides is contraindicated or unavailable. Trimethoprim-sulfamethoxazole has been used in oral doses of 8 to 12 mg/kg of the trimethoprim component and can be given either orally or intravenously. Nonspecific therapy is the same as that employed for patients with other forms of gram-negative sepsis and consists primarily of the treatment of shock, seizures, respiratory problems, and high fevers.

With present management, the mortality rate of plague is 14% in the United States. Bubonic plague has a mortality of 3% to 5%; the mortality with septicemic forms may exceed 50%, and pneumonic disease is almost universally fatal. Worldwide, untreated bubonic plague is fatal in 40% to 60% of cases. Complications not previously mentioned include a reactive arthritis, lung abscesses, and persisting lymphadenitis.


If pneumonic manifestations of the disease are noted, contacts of the patient should be quarantined and treated prophylactically with tetracycline. Preventive measures against the sporadic form of plague that occurs in the United States are not feasible because Y pestis is so widespread. However, in those areas of the world where the disease is transmitted by the rodent-flea-human cycle, continuous flea control accompanied by rodent controls are indicated.

An inactivated whole-cell vaccine is recommended only for those persons whose occupation regularly places them at high risk. Duration of immunity following three intramuscular doses given over 6 months is probably brief, and the safety of the vaccine has been tested only in those 18 years of age or older.