By Heather Frye-Ginsberg

Plague; Etiological agent - Yersinia pestis




Human susceptibility to infection is either direct or indirect. Indirect through the bites of an infected flea between, plague infected rodents and humans. (1) Direct infection from the plague can result from handling, skinning or cutting up the meat of a plague infected rodent or animal. Penetration of the organism can occur through the mucous membranes of the mouth, eyes, nose or subcutaneously, via skin lesions. (7)




Circulates in animal reservoirs, particularly rodents. Transmission occurs via wild rodent flea (bites), cannibalism, or contaminated soil. The bacteria, multiplies in the gut and causes the fleas to regurgitate onto the next animal. Also spread by people via respiratory droplets.


General Characteristics:


Gram-negative, non-motile, non-acid-fast, non-sporeforming, coccobacillus. Plague can be identified using several testing methods. The plague microbe measures 1.5 by 0.75 microns, and exhibits low resistance to environmental factors. Y. pestis grows on solid media as grey-white, translucent colonies (usually too small to be seen as individual colonies) after 24 hours. After 48-72 hours of incubation at 37°C, colonies appear raised, and have an irregular, “hammered copper appearance.” Cultures are identified by specific phage lysis. Stained sputum specimens normally contain polymorphonuclear cells (PMNs), and when stained with aniline dyes, bacillus ends present bipolar (best seen on Wayson- or Giemsa stain. Smears should be submitted for direct fluorescent antibody testing (anti-F1 antibody).  If colonies are not isolated, Y. pestis can be confirmed by a seroconversion (four-fold or greater titre change) to Y. pestis F1 antigen by passive haemagglutination testing of paired serum specimens. Positive passive haemagglutination requires confirmation with F1 antigen haemagglutination-inhibition test. Immunosorbent assays (ELISAs) can also be used for detecting IgM and IgG antibodies for antigen capture. (7)


Historical Information:


Plague, the “Black Death” killed a third of the population of Europe in the Middle Ages. It is believed that Y. pestis has evolved from the enteropathogen Y. pseudotuberculosis. The two are nearly identical genetically but produce two totally different diseases. Yersinia pestis was first identified by, Alexandre Yersin, in 1894.


Signs and Symptoms:


Infection causes febrile illness characterized by headache, myalgia, malaise, shaking chills, prostration, and gastrointestinal symptoms. The disease spreads to the regional lymph nodes then on to spleen, liver, lungs (meninges, pneumonia) and death.


Plague has several different forms: bubonic, pestis minor, pneumonic or septicemic. Emergence of bubonic plague, the most common form typically displays symptoms 2 to 6 days after initial exposure. A bubo (the name “Bubonic”) is formed and appears in the groin, neck, and armpits, and after a 2 week period may drain pus. Chills, a fever of up to 106°F, weak heartbeat and low blood pressure occur suddenly. Hemorrhages darken the skin (the name “Black Death”). When left untreated, most individuals will die between the third to fifth day. (2)


Once infected with the pneumonic form, symptoms begin abruptly and within 1 to 3 days after exposure. The symptoms include: high fever, chills, rapid heartbeat, and severe headache. Within 24 hours a cough develops producing clear sputum eventually streaked with blood, until bright red and foamy. Breathing is labored and most untreated people die within 48 hours. (2)


Septicemic plague is infection that has spread into the blood, (caused by bite but no bubo forms) when symptoms are present they include vomiting, diarrhea and abdominal pain. Without treatment, organ failure and death may occur. (2)


Pestis minor is a mild variation of the bubonic plague which symptoms include, swollen lymph nodes, fever, headache and exhaustion, normally disappearing within one week. (2)


Virulence Mechanisms:


The acquisition of genetic material, such as pathogenicity islands and plasmids improve its ability to overcome host defenses. Y. pestis has evolved, gained virulence factors, and morphed from an enteric to a systemic pathogen. The organism possesses a large plasmid, pCD1, encoding type III protein secretion system, pPst (carries gene encoding plasminogen activator) and pFra (encodes capsular F1 antigen and mureine toxin). (7)


The primary virulence factor in the extracellular lifestyle of Y. pestis is to hinder host innate immunity response and phagocytosis, allowing the unrecognized bacteria to multiply and spread throughout the host. Phagocytosis is the most important immune response mechanism used in protection and eradicating of a plague infection, and is paralyzed in the host upon intra-dermal infection. The Y. pestis relies on unregulated expression of capsular F1 protein and extracellular phagocyte-resistant bacilli for virulence. (6) Virulence genes such as, the haemin storage (hms) gene location is required for flea transmission but not for virulence in the mammalian host. (7) Fleabite transmission bacteria, is stored in an insect gut at ambient temperature and presents a different form of Y. pestis than does that of person-to-person transmission, grown in the human lung at 37°C. (6) The route of infection is an important factor in Y. pestis, and temperature is important in the regulation gene expression. YopM binds to human a-thrombin and is thought to produce the hemorrhagic lesion. Transcription and secretion of Yops, (effectors in pCD1 type III secretion operon) is present only at 37°C. At low temperatures the bacteria can multiply but does not secrete toxins. (7)


Control /Treatment:


Although antibiotic multi-resistant strains are emerging, most patients respond well to antibiotic therapy. Treatment must begin immediately, if plague is suspected (prior to laboratory confirmation). Drug classes such as, Aminoglycosides, Chloramphenicol, Tetracyclines, Sulfonamides, or Flouroquinilones are used for treatment. Treatment can include an injection of the antibiotic Steptomycin (most effective, drug of choice) for 7 to 10 days or antibiotics such as gentamicin, doxycycline, and ciprofloxacin. Infected individuals must be isolated to prevent the infection of others via the transmission of bacteria through the air, otherwise known as respiratory isolation.




Individuals in contact with an infected person or animal must take doxycyclin or ciprofloxacin for 7 days. Persons traveling abroad where plague outbreaks are prevalent should take antibiotics such as, doxycycline, trimethoprisulfamethoxazole, or ciprofloxacin. (2)


The vaccination for the Plague is no longer available in the United States. However, a live attenuated and formalin-killed Y. pestis vaccine has been used for humans. The vaccine does not protect against pneumonic plague, and one month or more is required for protective immune response, which makes the vaccine of little use during a human plague outbreak. The vaccine is used for persons in close contact with Y. pestis, such as lab technicians and or research persons studying infected rodent colonies. (7)


Current Information:


Globally the World Health Organization reports 1,000 to 3,000 cases each year. (1)

In the past 44 years, three periods of increased plague activity have occurred. The first increase occurred in the mid to 1960s, the second between 1973-1978, and the third from the mid-1980s. (7)


During 1980-1994, a total of 18,739 cases of the plague in humans were reported to WHO from 20 countries. A rise in plague morbitity continued worldwide in the 1990s. (4)


247 human plague cases were reported in the United States during 1980-1997, the highest of any 18-year period since the epidemic years in the early part of the century. Thirty-seven patients died. Much of this is attributed to rapid sub-urbanization and increasing numbers of people living near or in plague areas of concern. (7)


In the United States, the last urban plague (rat-bourne) epidemic took place in Los Angeles, California in 1924-25.  Human plague in the United States has occurred sporadically in rural areas at an average of 10 to 15 persons each year.  Two regions of the United States display the most human cases: 1) northern New Mexico, northern Arizona and southern Colorado and 2) California, southern Oregon, and far west Nevada. Plague also occurs in Africa, Asia, and South America. (1)


In 2006, 13 human plague cases were reported in four states within the United States: New Mexico (7 cases), Colorado (3 cases), California (2 cases), and Travis County, Texas (1 case). Since 1994, this was the largest number of plague cases reported within one year. (3)


A child in New Mexico died in June of 2009. He and his sister apparently contracted plague from fleas the dog brought home. No flea control had been applied to the dog, and it slept with the children.  (8)


The decrease in the plague today is primarily due to improved living standards and health care availability in many countries. The most epidemic form of the disease, the primary pneumonic plague has been reduced to nearly zero. (7)


Works Cited:


1.         “Plague.” Division of Vector-Borne Infectious Diseases. Department of Health and Human Services: Centers for Disease Control and Prevention. Last reviewed June 25, 2009. 1 Dec 2010.


2.         “Plague.”  Merck Manual Online Medical Library, Home Edition. Merck and Co, Inc.. Last reviewed Sept 2008. 1 Dec 2010.


3.         “Human Plague—Four States 2006.” Department of Health and Human Services: Centers for Disease Control and Prevention. August 2006/55(Dispatch);1-3. 1 Dec 2010.


4.         “Prevention of the Plague: Recommendations of the Advisory Committee on Immunization Practices (ACIP).” December 1996./45 (RR-14);1-15.  1 Dec 2010.


5.         “WHO-Initiative for Vaccine Research (IVR).” 1 Dec 2010.


6.         Smiley, Stephen T. “Current Challenges in the Development of Vaccines for Pneumonic Plague.” Posted: 07/16/2008; Expert Rev Vaccines. 2008;7(2):209-221. 2 Dec 2010.


7.         “Plague Manual: WHO: Epidemiology, Distribution, Surveillance and Control.” WHO/CDS/CSR/EDC/99.2. 1 Dec 2010.


8.         “Plague.” Texas Health Service Region 1 News Department of State Health Services. Summer 2010. 6 Dec 2010