Plague is infectious disease that can affect humans and animals. This disease is caused by Yersinia pestis (yer-sin'e-a pes'tis). Yersinia is a gram-negative rod-ovoid 0.5-0.8 micrometer in width and 1-3 micrometer in length. This bacterium is facultative intracellular non-motile parasite. In the Middle Ages, this disease was known as Black Death. This term came from one of the characteristics of this disease: dark blue areas of skin caused by hemorrages (1,2,9).
Yersinia pestis has probably killed more people that any other bacterium. It killed one quarter of the whole European population in the 14th century, and 100 millions in the 6th century. The British epidemic of 1665 killed 70,000 people. The last great plague pandemic, which started in Hong Kong in 1893, killed more than 20 million people (1,2).
Normally, Plague is the disease of rats that is transmitted from one rat to another by the rat flea, Xenophilla cheopis. In the US, this disease is endemic in wild rodents like ground squirrels and prairie dogs. When the host dies, the flea seeks a replacement host, which may be another rodent or human. Also, this disease can be transmitted by airborne droplets from humans or pats, with plaque pneumonia, and by careless manipulation of laboratory cultures (2,3,9).
There are three forms of plague in humans: bubunic, septicaemic and pneumonic (the most severe one). Bubonic plague (incubation period is 2-10 days) is the result of an insect bite. After human is bitten with an infected flea, Yersinia pestis is released into the organism. Then this bacterium travels to the nearest lymph node and causes it to enlarge. Such swellings are called buboes. Also, fever, chill, pain of the lymph nodes, headache, weakness, difficulty breathing, dyspnea, pneumonia, enteric fever syndrome, abdominal pain, lymphadenopathy and subcutaneous hemorrhages can develop as a result of this infection. The bacteria can enter the blood stream and proliferate, causing septic shock. This dangerous condition is called Septicemic plague. It can occur by itself or can be complication of bubonic or pneumonic plague. Signs and symptoms of this condition are similar to bubonic plague but buboes do not develop. Usually, patients have fever, chill, prostration, abdominal pain, shock, and bleeding into skin and other organs. (Septicemic plague as well as Bubonic plague does not spread from person to person). Pneumonic plague develops when bacteria are carried by the blood stream to the lungs. (If bubonic and septicemic conditions of plague are not treated, they may develop into pneumonic plague). This is the most dangerous condition of plague (mortality rate is 100% of untreated cases). Pneumonic plague can be transmitted from person to person by air droplets. It progresses rapidly because its incubation period is just 2-3 days. This condition of plague results in high fever, chill, headache, pneumonia, dyspnea, cough, hemorrhagic necrosis of the lung, cyanosis and finally death (3,4,5,6).
Yersinia pestis has several important virulence factors. First of all, it has antiphagocytic capsule (fraction 1 or Fra 1 gene). Second, it has plasminogen activator (Pla) gene that degrades complement components C3b and C5a. Third, this bacterium produces endotoxins. Forth, it has proteins: Invasin and Yad A that help this bacterium attach to eukaryotic cell surface. If Yersinia pestis is placed at 37 degrees C and in a nutrient rich environment, a plasmid (70-kbps called pYV), which encodes the Yop (Yersinia Outer Membrane Proteins) virulon, and a type III secretion apparatus called Ysc or Yersinia secretion are transcribed, and the mRNA transcripts are translated. There are 29 different Ysc proteins, which can form a pore in the inner and outer membrane of the bacterium. It helps the bacterium reach the eukaryotic cell's cytoplasm. There are six different effector Yops that can inhibit phagocytosis, inflammation, and induce apoptosis of macrophages when Yersinia pestis is inside of the eukaryotic cell (1,5,6,7).
The cultures of Yersinia pestis have several distinctive characteristics. They are gray-white irregular colonies that have "fried egg" appearance. These colonies have "hammered copper" shiny surface. When cultured on sheep blood agar, Yersinia pestis produces little or no hemolysis (gamma hemolytic). And when cultured on selective media MacConkey (MAC) or Eosin methylene blue (EMB), this bacterium grows in small non-fructose fermenting colonies. Sometimes Yersinia pestis is grown in the broth tubes (Brain heart infusion). In this case, it appears as a "stalactite" (8).
In the case with pneumonic plague, we should take bronchial wash or transtracheal aspirate (>1ml) to isolate this bacterium for culture and Fluorescent antibody (FA) assay. Supportive tests like X-rays are very helpful. When a person is suffering from bubonic plague, tissue from internal organs, such as liver, spleen, bone marrow or lung, should be examined. Liver function tests (LFT 's) are common. And finally, to isolate Yersinia pestis from the person who has septicemic condition of plague, blood should be collected for F1 antigen assay (must use fresh specimens to avoid false negatives), PCR, serological tests and for gram stain. To identify this bacterium, several tests must be conducted. First of all, gram stain gives us presumptive identification (gram negative rods can be single, in pairs or in rods). Then Write-Glemsa and Wayson stains should be used to highlight bipolar characteristics of Yersinia pestis gram negative rods. Yersinia pestis appears as light blue bacilli with dark blue polar bodies on a contrasting pink ground (1,7,8).
After that four additional tests must be conducted:
Oxidase: (negative)
Catalase: (positive)
Urea: (negative)
Indole: (negative)
There are several antibiotics that can kill Yersinia pestis. Sreptomycin or gentamicin are the preferred antibiotics. Tetracyclines, fluoroquinolones or chloramphenicol are alternative choices. Co-trimoxazole is recommended for pregnant women and children between the ages of 2 months and 8. Early treatment of plague is essential. For example, if antibiotics are not given to the person, who has pneumonic plague within 24 hours since the first symptoms developed, this person can die. Also, once someone has been exposed to a plague victim (animal or human), prophylactic (disease-preventing) antibiotics must be given. All suspected victims of plague require hospital treatment. Once in the hospital, these patients are isolated immediately, and hospital personnel take special precautions (gloves, masks, protective clothing, etc.) to prevent the spread of plague bacteria. The infection is treated with at least 10 days of antibiotics given intravenously or orally (8).
To prevent plague, killed bacteria have been used in plague vaccines since 1896. However, only one vaccine, a formalin-inactivated preparation, is currently licensed for use in the United States. This vaccine (plague vaccine, USP) is now available only from Greer Laboratories, Inc. The killed or inactivated plague vaccine is prepared from Yersinia pestis organisms grown in artificial media and then inactivated in formaldehyde. Live Yersinia pestis vaccines composed of avirulent strains also have been developed. However, none of these vaccines is commercially available because there is possibility that it can cause a disease. Unfortunately, even though vaccine is available, evidence supports its effectiveness against the bubonic form only, but not necessarily against pneumonic plague (6,8).
Nevertheless, to prevent plague, a formalin-inactivated vaccine should be available for adults (18-61yrs old) at high risk (vaccination of the whole population is not recommended because it frequently causes severe inflammatory reactions). At the same time, flea and rat control is necessary. Also, people should avoid contact with sick or dead animals (especially rodents) and report about these animals to local health authorities. People should fight flea on their cats and dogs using different flea repellents. If somebody lives in a high-risk area, he/she should check with local health authorities about effective rodent-proofing strategies and keeping your property free from brush, rocks, garbage and food waste that may attract rodents (5,7,8).
References:
1. Dr. Chemberlain, "Plague", 07/30/01 http://www.kcom.edu/faculty/chamberlain/Website/lectures/lecture/plague.htm 05/03/02
2. Dr. Mark, "Plague", 02/02/00: http://www.ento.vt.edu/IHS/plague.html 04/28/02
3. CDC Plague Home Page, 06/22/01: http://www.cdc.gov/ncidod/dvbid/plague/index.htm 05/02/02
4. "Yersinia pestis", 04/09/99: http://medinfo.ufl.edu/year2/mmid/bms5300/bugs/yerpest.html
5. "Plague" (fact sheet N 267), January 2002 http://www.who.int/inf-fs/en/fact267.html 04/29/02
6. "Plague", 08/30/01: http://www.niaid.nih.gov/newsroom/focuson/bugborne01/plague.htm 04/30/02
7. "Yersinia pestis", 01/14/02: http://www.bacteriamuseum.org/species/ypestis.shtml 05/04/02
8. "Level A Laboratory Procedures for Identification of Yersinia Pestis," 12/13/01: http://www.bt.cdc.gov/Agent/Plague/Plague20010417.pdf 05/05/02
9. Tortora, Funke and Case. "Microbiology, an Introduction." (7th Ed.) Publisher: Longman, Inc., Addison Weslay, 2001.