Y. pestis is the cause of plague, also known as the black death, the scourge of the Middle Ages. It is also a contemporary disease, occurring in the western United States and in many other countries around the world. Two less important species, Yersinia enterocolitica and Yersinia pseudotuberculosis, are described in Chapter 27.
Y. pestis is a small gram-negative rod that exhibits bipolar staining (i.e., it resembles a safety pin, with a central clear area). Freshly isolated organisms possess a capsule composed of a polysaccharide–protein complex. The capsule can be lost with passage in the laboratory; loss of the capsule is accompanied by a loss of virulence. It is one of the most virulent bacteria known and has a strikingly low ID50 (i.e., 1–10 organisms are capable of causing disease).
Pathogenesis & Epidemiology
The plague bacillus has been endemic in the wild rodents of Europe and Asia for thousands of years but entered North America in the early 1900s, probably carried by a rat that jumped ship at a California port. It is now endemic in the wild rodents in the western United States, although 99% of cases of plague occur in Southeast Asia.
The enzootic (sylvatic) cycle consists of transmission among wild rodents by fleas. In the United States, prairie dogs are the main reservoir. Rodents are relatively resistant to disease; most are asymptomatic. Humans are accidental hosts, and cases of plague in this country occur as a result of being bitten by a flea that is part of the sylvatic cycle.
The urban cycle, which does not occur in the United States, consists of transmission of the bacteria among urban rats (the reservoir), with the rat flea as vector. This cycle predominates during times of poor sanitation (e.g., wartime), when rats proliferate and come in contact with the fleas in the sylvatic cycle.
The events within the flea are fascinating as well as essential. The flea ingests the bacteria while taking a blood meal from a bacteremic rodent. A thick biofilm containing many organisms forms in the upper gastrointestinal tract that prevents any food from proceeding down the gastrointestinal tract of the flea. This “blocked flea” then regurgitates the organisms into the bloodstream of the next animal or human it bites.
The organisms inoculated at the time of the bite spread to the regional lymph nodes, which become swollen and tender. These swollen lymph nodes are the buboes that have led to the name bubonic plague. The organisms can reach high concentrations in the blood (bacteremia) and disseminate to form abscesses in many organs. The endotoxin-related symptoms, including disseminated intravascular coagulation and cutaneous hemorrhages, probably were the genesis of the term black death.
In addition to the sylvatic and urban cycles of transmission, respiratory droplet transmission of the organism from patients with pneumonic plague can occur.
The organism has several factors that contribute to its virulence: (1) the envelope capsular antigen, called F-1, which protects against phagocytosis; (2) endotoxin; (3) an exotoxin; and (4) two proteins known as V antigen and W antigen. The V and W antigens allow the organism to survive and grow intracellularly, but their mode of action is unknown. The action of the exotoxin is unknown.
Other factors that contribute to the extraordinary pathogenicity of Y. pestis are a group of virulence factors collectively called Yops (Yersinia outer proteins). These are injected into the human cell via type III secretion systems and inhibit phagocytosis and cytokine production by macrophages and neutrophils. For example, one of the Yops proteins (YopJ) is a protease that cleaves two signal transduction pathway proteins required for the induction of tumor necrosis factor synthesis. This inhibits the activation of our host defenses and contributes to the ability of the organism to replicate rapidly within the infected individual.
Bubonic plague, which is the most frequent form, begins with pain and swelling of the lymph nodes draining the site of the flea bite and systemic symptoms such as high fever, myalgias, and prostration. The affected nodes enlarge and become exquisitely tender. These buboes are an early characteristic finding. Septic shock and pneumonia are the main life-threatening subsequent events. Pneumonic plague can arise either from inhalation of an aerosol or from septic emboli that reach the lungs. Untreated bubonic plague is fatal in approximately half of the cases, and untreated pneumonic plague is invariably fatal.
Smear and culture of blood or pus from the bubo is the best diagnostic procedure. Great care must be taken by the physician during aspiration of the pus and by laboratory workers doing the culture not to create an aerosol that might transmit the infection. Giemsa or Wayson stain reveals the typical safety-pin appearance of the organism better than does Gram stain. Fluorescent antibody staining can be used to identify the organism in tissues. A rise in antibody titer to the envelope antigen can be useful retrospectively.
The treatment of choice is a combination of streptomycin and a tetracycline such as doxycycline, although streptomycin alone can be used. Levofloxacin can also be used. There is no significant antibiotic resistance. In view of the rapid progression of the disease, treatment should not wait for the results of the bacteriologic culture. Incision and drainage of the buboes are not usually necessary.
Prevention of plague involves controlling the spread of rats in urban areas, preventing rats from entering the country by ship or airplane, and avoiding both flea bites and contact with dead wild rodents. A patient with plague must be placed in strict isolation (quarantine) for 72 hours after antibiotic therapy is started. Only close contacts need to receive prophylactic tetracycline, but all contacts should be observed for fever. Reporting a case of plague to the public health authorities is mandatory.
A vaccine consisting of formalin-killed organisms provides partial protection against bubonic but not pneumonic plague. This vaccine was used in the armed forces during the Vietnam War but is not recommended for tourists traveling to Southeast Asia.