Plague

• Plague

  Caused by the bacterium Yersinia pestis
• Yersinia pestis


  Rod-shaped bacteria of the family Enterobacteriaceae, gram-negative and facultative anaerobes
• Yersinia pestis

  • Has two main habitats: (i) the gut of a flea, at ambient temperature (ii) blood or tissues of a mammalian host, at body temperature
• Natural Hosts and Vectors for plague

  • Rats and other rodents
  • Marmots (Mongolia)
  • Gerbils (Africa)
  • Ground squirrels, chipmunks and prairie dogs (North America)
  • Wild guinea pigs (South America)
• Brown rat (Rattus norvegicus)


  The link between wild and domestic rodents
• Black rat (Rattus rattus)

  Usually the source of human infection, very susceptible to plague
• Rat flea (Xenopsylla cheopis)


  The most important vector for plague transmission
• Insect vectors for plague

  • Estimated 2,500 species and subspecies of fleas - constituting 220 genera and 15 families in insect order Siphonaptera
  • Approximately 80 species have been found to be infected with Y. pestis in the wild and/or susceptible to experimental infection
• Transmission by the flea

  1. Vectors become infected following uptake of a blood meal

  2. Pathogen replicates and disseminates in the vector

  3. Y. pestis remains confined to the flea digestive tract and is transmitted by regurgitation

  4. Y. pestis does not adhere to, or invade, the midgut epithelium

  5. Y. pestis persistence in the flea depends on (i) formation of multicellular aggregates AND (ii) their ability to form a biofilm and which creates a blockage in the proventriculus

  6. Blocking the proventricular valve enhances regurgitative transmission of the bacterium
• Pathogenicity of Yersinia pestis

  • Highly pathogenic in humans, able to overcome host defences and multiply within the body (mainly) extracellularly
  • Induces a local lesion and inflammation, followed by rapid spread and multiplication
  • Toxins produced by Yersinia cause most of the harm - endothelial damage and necrosis, leading to vascular destruction and local haemorrhaging
• Three major recorded plague pandemics through history

  • 541 - The Justinianic Plague
  • 1347 - The Black Death
  • 1894 - Modern Plague
• The Justinianic Plague began in 541 AD and was followed by frequent outbreaks over the next two hundred years – estimated to have killed over 25 million people around the Mediterranean basin
• The Black Death originated in China in 1334 and spread along great trade routes to Constantinople (now Istanbul) and then on to Europe – estimated to have killed 30-50% of the European population
• The Modern Plague began in China in the 1860s and appeared in Hong Kong by 1894. Over the next 20 years, it spread to port cities around the world – estimated to have caused approximately 10 million deaths
• The medieval plague led to large and long-lasting increases in the purchasing power of wages and higher levels consumption and standards of living for those that survived
• COVID-19 2019-20?? has had very high case fatality rates with consequent high mortality (40-75%), but not as devastating as the historical plague pandemics
• Between 2010-2015, there were 3248 cases of plague reported worldwide, including 584 deaths (WHO)
• Palaeogenetic research has shown that ancient plague was not the same as more recent plague, the pathogen is constantly evolving
• The deliberate release of 50 kg of Yersinia pestis in an aerosolised form over a city of 5 million could result in pneumonic plague in up to 150,000 people and 36,000 deaths
• Symptoms of plague

  • Bubonic plague
  • Septicaemic plague (Black Death)
  • Pneumonic plague
• Bubonic plague


  The most common form, initiated by infected flea bite, bacteria enter body and multiply at site of entry in skin then spread via lymphatic system to lymph nodes, forming painful and enlarged buboes
• Septicaemic plague (Black Death)

  Bloodstream infection - meningitis, endotoxic shock and disseminated intravascular coagulation (DIC), leading to gangrene of the extremities and multi-organ failure
• Pneumonic plague

  Least common, but most virulent form, typically caused by infection spreading to lungs in advanced bubonic plague
• Mortality rate for bubonic plague (if untreated) is 50-60%, but if infected person recovers, they are immune to further infection
• Mortality rate for septicaemic plague (if untreated) is 100%
• Mortality rate for pneumonic plague (if untreated) is 100%
• Bubonic plague

  1. Bacteria enter body and multiply at site of entry in skin

  2. Spreads via the lymphatic system to lymph nodes

  3. Lymph nodes become painful and enlarged - forming buboes

  4. Onset of fever is abrupt and often accompanied by chills

  5. Infected people can become delirious and confused

  6. Buboes may suppurate i.e. burst to form open sores
• Buboes


  Swellings in the lymph nodes (Medieval Latin - bubo = swelling)
• Mortality rate (if untreated) of bubonic plague is 50-60%
• If an infected person recovers, they are immune to further infection
• Septicaemic plague (Black Death)

  1. Septicaemia (blood poisoning) occurs when infection spreads to bloodstream

  2. Can result from flea bites and also from direct contact with infective material

  3. Bubonic plague can also develop into secondary septicaemic plague

  4. Bloodstream infection - meningitis, endotoxic shock and disseminated intravascular coagulation (DIC)

  5. DIC - systemic activation of blood coagulation leads to gangrene of the extremities and multi-organ failure
• Mortality rate (if untreated) of septicaemic plague is 100%
• Pneumonic plague

  1. Infection spreads to lungs in advanced bubonic plague, or can result from person-person transmission

  2. Causes acute pulmonary insufficiency, sepsis and toxic shock

  3. Death usually ensues if treatment is not begun within 18-24h of disease onset - even then the mortality rate remains extremely high
• Pneumonic plague is the least common, but most virulent form of the disease (case-fatality 100%)
• Plague is most often transmitted by bite of an infected flea
• Plague can also be transmitted by contact with contaminated fluid or tissue
• Pneumonic plague can be transmitted through infectious droplets coughed by an infected person
• Yersinia pestis is very sensitive to sunlight and heat, and so does not survive long outside a host
• There is no evidence that Yersinia pestis surviving in soil poses an environmental risk to humans
• Diagnosis of plague

  1. Visualization of bipolar-staining, ovoid, Gram-negative organisms allows a rapid presumptive diagnosis

  2. Specimens can be obtained from lymph nodes, blood, sputum, or bronchial/tracheal washing

  3. When live organisms are unculturable, tissues may yield evidence of plague infection e.g. antigen detection or PCR