Y. pestis is a pleomorphic, nonmotile, gram-negative bacillus of the family Enterobacteriaceae. When the bacillus is stained with Gram, Giemsa, or Wayson stain, it reveals a bipolar morphology. Y. pestis grows best on brain-heart infusion and MacConkey agar. Positive cultures show pinpoint colonies within 24 to 48 hours after inoculation. However, laboratories that are fully automated or semiautomated may not detect Y. pestis.

Y. pestis grows optimally at 28°C. Organisms can be isolated from blood, sputum, cerebrospinal fluid, feces, urine, or aspirates of enlarged lymph nodes. These body fluids can be examined for the typical bacilli. Isolated bacteria can be identified by their nonmotile activity at 37° and 22°C. Usually, the organism is negative for urea hydrolysis, but it may be positive in freshly isolated specimens. The response is positive for catalase, nitrate, methyl red, esculin, and beta-galactosidase. The indole, oxidase, and Voges-Proskauer reactions are negative. Y. pestis ferments maltose, xylose, glucose, arabinose, salicin, dextrin, mannitol, and trehalose. It does not produce acid from lactose, sucrose, rhamnose, melibiose, adonitol, cellobiose, sorbose, or dulcitol. Y. pestis does not use citrate or grow in potassium cyanide, nor does it respond to lysine, ornithine decarboxylase, or arginine dihydrolase.

The organism can be identified by lysis of the isolate by known strains of bacteriophage, agglutination with specific Y. pestis antiserum, animal inoculation, and detection of fraction 1 antigen by fluorescent antibody staining. The genome of Y. pestis has been sequenced. Polymerase chain reaction (PCR) is available for detection of the plasminogen activator gene of Y. pestis. A rapid PCR has been developed that can detect 10² colony-forming units (CFUs) of Y. pestis in sputum 5 hours after the sample is collected.

The virulence of Y. pestis strains varies, depending on the development of the envelope of fraction I antigen, absorption of hemin from medium, production of V and W antigens, synthesis of purines, and generation of toxins. The presence of a fraction I envelope or V and W antigens renders the strain resistant to phagocytosis and permits the organism to multiply. A plasmid of 9-kb pairs contains the determinant of secretory protein that kills other bacterial strains. A plasmid of 72-kb pairs, which all pathogenic Y. pestis strains contain, confers the requirement for environmental calcium, which is necessary for the organism to grow at 37°C. When grown under this condition, Y. pestis produces the V and W antigens necessary for virulence. Toxins have been produced by all fully virulent strains. Endotoxin and exotoxin appear to contribute to the morbid effects of plague. Transferable plasmid-mediated resistance, including multidrug transport systems, has been isolated.

Historically, plague typically was transmitted by fleas that had fed on infected rats. This form of transmission is more likely to occur in urban, rat-infested, and crowded dwellings and may result in epidemics. In the United States, this form of spread rarely occurs where plague is transmitted to humans after contact with an enzootic focus. Wild rodents perpetuate the plague bacillus by virtue of their ability to withstand an inoculum of Y. pestis many times greater than that which causes disease in domestic animals or humans. After being inoculated, the wild rodent becomes bacteremic and can infect the fleas that feed on it. The fleas then can transmit the plague bacillus to another rodent. Hibernating animals are particularly resistant to clinical infection and, if inoculated before going into hibernation, may survive the winter and succumb to the infection only after they emerge from their burrows, thus carrying the bacillus into a new season. Carnivores are relatively resistant to infection but contribute to the spread of the organism by transporting infected fleas from one area to another.

Plague is transmitted to humans by the bite of an infected flea, the inhalation of infected droplets from a patient with pneumonic plague, or the skinning and evisceration of infected animals. Rarely, Y. pestis can enter through the conjunctiva and the pharynx. Assymptomatic transient pharyngeal carriage has been described in contacts of bubonic plague cases; the incidence of this carriage is unknown.

Domestic animals play a significant role in bridging the gap between sylvatic plague and human infection. Cats and dogs are susceptible to both natural and experimental plague. Between 1977 and 1998, 23 cases of feline-associated human plague infection were reported. Epizootics in cats have been observed in conjunction with plague epidemics in humans. Domestic animals’ fleas are more likely than are rodent’s fleas to bite humans. The Oriental rat flea is the most efficient transmitter of the plague bacillus because of the frequency with which it bites humans and its propensity for regurgitating large numbers of Y. pestis in the process of biting. Because cats and dogs
are susceptible to natural and experimental plague and because of their extensive contact with humans, domestic animals may be responsible for some cases of human plague.

Sylvatic plague depends on the rodent flea as a vector. This flea is not as efficient as a rat flea in transmitting Y. pestis, but it may become a reservoir of the organism by surviving for a year or more after the original host dies. Between epizootics, Y. pestis can survive in soil, which may serve as a means for transmission of plague.

In urban areas, the organism usually is introduced from an enzootic population into a susceptible rat population. In areas where humans and rats live in proximity, an epizootic in rats may be followed by an epidemic in people. In the United States, children become infected by direct contact with a sylvatic reservoir of this infection. Adult cases are the result of working or hunting in plague-infected areas.

The portal of entry of the Y. pestis organism determines the form the disease takes. The most common site of entry is the skin, after the bite of an infected flea has occurred. Broken skin provides an easy route for direct inoculation while handling infected animals. After the organism has bypassed the skin barrier to cause infection, it moves by lymphatics to regional lymph nodes. The infection may be localized at this site, with subsequent formation of antibodies and ultimate recovery of the patient. This form of the disease has been called pestis minor.

Frequently, Y. pestis is disseminated through the bloodstream. Involvement of the liver, spleen, lungs, kidneys, and meninges may occur. Disseminated intravascular coagulation, a common finding in fatal cases, includes an elevation of split-fibrin products, thrombocytopenia, and fibrin deposition in the glomeruli.

The major determinant of the severity of the disease appears to be the presence of high levels of circulating endotoxin. Virulent Y. pestis organisms are phagocytized but are not killed. They replicate unimpeded in macrophages, permitting the accumulation of endotoxin.

If the primary portal of entry is the lung, the resulting disease usually is fulminant. Plague bacilli can replicate freely in the alveolar spaces, resulting in severe and overwhelming pneumonitis, septicemia, and endotoxemia. In fatal cases, lymph nodes in the thoracic region have shown infarction, liquefaction necrosis, and formation of pus. The mucosa of the trachea and bronchi may be covered by a frothy, bloody exudate. Submucosal hemorrhages and necrotic areas surround the trachea. Pleural surfaces contain hemorrhagic lesions and fibrinous adhesions. The lung may show signs of acute edema or consolidation. The most prominent histologic feature is an alveolar exudate consisting of polymorphonuclear leukocytes and histiocytes. The kidneys may appear grossly hemorrhagic, and areas of necrosis may be evident. Glomeruli with fibrin thrombi are found frequently in patients who have disseminated intravascular coagulation.

The incubation period of Y. pestis is approximately 3 or 4 days, but it can be as short as 1 to 2 hours or as long as 2 weeks. The onset of illness usually is abrupt, beginning with malaise, headache, fever, and weakness. Often, fever is accompanied by shaking chills. Development of a visible or palpable mass of nodes, known as a bubo, may be preceded by tenderness or pain at the site.

On physical examination, the patient appears to be apprehensive, toxic, and tachycardiac. The site of inoculation at the skin may or may not be evident. In some cases, the inoculation site is covered by a carbuncle. In bubonic plague, large, fixed, tender, and edematous lymph nodes are evident at one anatomic site. The areas of nodal involvement are the groin, axilla, and neck, in decreasing order of frequency. Any involved lymph node, including the intraabdominal nodes, can suppurate, which may produce the picture of an acute abdominal emergency.

Neurologic manifestations resulting from the effects of toxin on the brain are common findings. Patients with plague may report insomnia or may suffer from weakness, delirium, stupor, gait disturbances, disorders of speech, loss of memory, or vertigo. Meningitis may occur. Children younger than 15 years of age seem to be more susceptible, and septicemic patients are four times more likely to develop meningitis than are patients with bubonic plague. Meningitis often manifests itself while the patient is well into a course of antibiotic therapy for bubonic or septicemic plague. Intravascular coagulation may herald the onset of renal involvement, which can present clinically as an acute cortical or tubular necrosis. Involvement of the liver is evidenced by mildly elevated liver enzymes.