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Pathogen of the Month: Yersinia Pestis

by Dr. Jaclynn Moskow

The most researched pathogen on GIDEON in January was Yersinia pestis, a facultative anaerobic, Gram-negative, coccobacillus. It is the causative agent of the Plague and responsible for some of the most deadly pandemics in history.  While Yersinia pestis is no longer a cause of mass mortality, outbreaks do still occur. Over the last decade, there have been up to 2,000 cases per year reported to the World Health Organization, and likely thousands more unreported.[1]

Yersinia pestis illustration
Yersinia pestis – the agent of Plague

Transmission

Rodents are the natural reservoirs for Yersinia pestis, including rats, mice, squirrels, chipmunks, voles, prairie dogs, and marmots. The bacteria can also be transmitted to a wide variety of other mammals, including rabbits, coyotes, sheep, and cats. There are currently animals carrying Yersinia pestis on all continents except for Oceania.[2]

Fleas transmit Yersinia pestis from animals to humans, and flea bites are the most common route of infection for humans. Humans can also become infected by coming into contact with fluid or tissue. For example, this could happen when a hunter skins a diseased animal. When respiratory infection occurs, Yersinia pestis can become airborne and spread between humans. In rare cases, Yersinia pestis has been contracted via ingestion of infected meat. Dr. Berger discusses transmission here

Both children and adults are at risk of becoming sick with Plague, and there does not appear to be a significant difference in infection rates between men and women.

Yersinia pestis in history

Yersinia pestis likely emerged around 6,000 years ago, evolving from a close relative – Yersinia pseudotuberculosis. [3] The first major Plague pandemic occurred in the 6th century and is known as The Justinian Plague. The disease spread throughout Europe, Asia, and North Africa by way of ship. Its death toll is disputed, with some researchers estimating it claimed half the world’s population and others believing it was less severe.[4]

The second major Plague pandemic occurred between 1346 and 1353, once again striking Europe, Asia, and North Africa. This outbreak, known as The Black Death, took the lives of 75 to 200 million people. It decimated cities quickly upon arrival, sometimes killing over half the population in just a few weeks. In Ragusa, a Venetian port city, incoming sailors were isolated for 40 days, a practice which was known as a “quarantino” …the origin of the word “quarantine”.[5]

Images of physicians wearing bird-like beak masks are often associated with The Black Death. Microbes had yet to be discovered, and many doctors believed Plague was transmitted through smell. To combat this smell, the beak mask had a space for flowers, herbs, and spices. This mask, however, was actually not invented during The Black Death, but rather during a different Plague outbreak in 1619. After the Black Death subsided, Plague outbreaks continued in Europe every few years for the next 300 years, culminating with “The Great Plague” of London in 1665.

 

 

The next significant Plague pandemic occurred in 1894, originating in China, spreading through Asia and Europe, and eventually arriving in the United States in 1900. In 1894 Swiss physician Alexandre Yersin and Japanese physician Kitasato Shibasaburō simultaneously discovered the bacterial origin of Plague. Yersin named the bacterium Pasteurella pestisSoon after, fleas were identified as a vector of transmission. Pasteurella pestis was renamed Yersinia pestis in 1944. Notable 20th-century plague outbreaks occurred in Los Angeles between 1924 to 1925 and in Vietnam from 1965 to 1975.

Bubonic Plague

There are 3 main types of Plague, with Bubonic Plague being the most common type. Bubonic Plague is transmitted via flea bites or via the handling of tissue or fluids. It has an incubation period of 2-to-6 days. Bacteria multiply in lymph nodes close to the site of infection. A maculopapular lesion may appear at the infection site. The lymph nodes become painful and swollen and are known as “Buboes.” Buboes are usually inguinal (60% to 90%), axillary (30%), cervical (10%), or epitrochlear (10%). Other symptoms of Bubonic Plague are flu-like, including fever, headache, chills, pharyngitis, muscle aches, extreme weakness, and tachycardia. Without treatment, Bubonic Plague has a mortality rate of around 50-60%. With treatment, this drops to about 10%. Human to human transmission of Bubonic Plague is extremely rare.

 

Bubonic plague transmission - illustration

 

Pneumonic Plague

Pneumonic Plague occurs when Yersinia pestis enters the lungs. This can happen from inhaling respiratory droplets, or from the bloodstream during untreated Bubonic Plague. The incubation period when the bacteria is inhaled is 1-to-3 days. Pneumonic Plague presents with fever, headache, weakness, tachycardia, coughing, chest pain, and shortness of breath. Hemoptysis is common. With treatment, it has a fatality rate of around 15%. Untreated Pneumonic Plague is almost always fatal.

Septicemic Plague

When Yersinia pestis enters the bloodstream, Septicemic Plague can occur. This may happen directly from a flea bite, or as a complication of untreated Bubonic or Pneumonic Plague. Septicemic Plague may begin with flu-like symptoms. Additionally, it may cause nausea, vomiting, diarrhea, abdominal pain, and sometimes hematemesis and/or hematochezia. Acrocyanosis, ecchymosis, petechiae, and digital gangrene may be noted. Septicemic Plague may progress to cause meningitis, osteomyelitis, kidney failure, DIC, and septic shock. The fatality rate is around 28% with treatment and around 100% if untreated.

Rare forms of Plague include cutaneous, pharyngeal, meningeal, and gastrointestinal.

Diagnosis and treatment

A presumptive diagnosis of Plague may be made through isolation of Yersinia pestis from pus, blood, sputum, or other infected material. 

When Plague is suspected, treatment should be initiated prior to laboratory confirmation. Gentamicin, Streptomycin, Doxycycline, and Chloramphenicol are all effective. Patients with Plague should be isolated. When Pneumonic Plague is suspected, standard respiratory droplet precautions should be followed. Individuals exposed to Plague patients should begin prophylaxis. 

Prevalence

Today, there are approximately 1,000 to 2,000 reported cases of Plague globally each year – and 100 to 200 deaths.

Plague deaths worldwide, GIDEON graph

 

About 95% of current Plague cases occur in Madagascar and the Democratic Republic of Congo.  Brazil, Myanmar, Peru, Vietnam, and The United States also report cases almost every year. If you have a GIDEON account, click to explore Plague outbreak map

According to the CDC, about 7 people in the United States contract Plague each year, with the areas reporting cases usually being Northern New Mexico, Northern Arizona, Southern Colorado, Southern Oregon, Western Nevada, and various rural and semi-rural parts of California.

In 2009, University of Chicago scientist Malcolm Casadaban contracted Plague while conducting vaccine research and unfortunately died. Between 2019 and 2020 there were at least 5 cases of Plague in China linked to eating marmot meat and a few others of unknown origin.

 

Prevention

People who live in areas with Plague outbreaks can take precautions to minimize the risk of infection. The CDC recommends the following:

  • Reduce rodent habitat around your home, workplace, and recreational areas. Remove brush, rock piles, junk, cluttered firewood, and possible rodent food supplies, such as pet-  and wild anima- food. Make your home and outbuildings rodent-proof.
  • Wear gloves if you are handling or skinning potentially infected animals to prevent contact between your skin and the plague bacteria. Contact your local health department if you have questions about disposal of dead animals.
  • Use repellent if you think you could be exposed to rodent fleas during activities such as camping, hiking, or working outdoors. Products containing DEET can be applied to the skin as well as clothing and products containing permethrin can be applied to clothing (always follow instructions on the label).
  • Keep fleas off of your pets by applying flea control products. Animals that roam freely are more likely to come in contact with plague infected animals or fleas and could bring them into homes. If your pet becomes sick, seek care from a veterinarian as soon as possible
  • Do not allow dogs or cats that roam free in endemic areas to sleep on your bed.

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References

[1] Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD), “Plague: Frequently Asked Questions”. [Online]. Available: https://www.cdc.gov/plague/faq/index.html#cases

[2] World Health Organization, “Plague”. [Online]. Available: https://www.who.int/health-topics/plague#tab=tab_1

[3] C Demeure, O Dussurget, G Mas Fiol, et al., “Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics”, Genes Immun, vol. 20, num. 5, pp. 357-370, 2019. Available: 10.1038/s41435-019-0065-0

[4] L Mordechai, M Eisenberg, T Newfield, et al., “The Justinianic Plague: An inconsequential pandemic?”, Proc Natl Acad Sci, vol. 116, num. 51, pp. 25546-25554, 2019. Available: 10.1073/pnas.1903797116

[5] P Mackowiak, P Sehdev, “The Origin of Quarantine”, Clinical Infectious Diseases, vol. 35, num. 9, pp. 1071–1072, 2002. Available: 10.1086/344062

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