Plague

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• BIOL 123 Infection and Immunity lecture 7


  11am Tuesday 30th January 2024
• Yersinia pestis


  The organism that causes the plague
• From this lecture and additional reading students should be able to:

  1. Name the organism that causes the plague

  2. Discuss the historical impact of plague on human populations

  3. Explain the common modes of plague transmission

  4. Differentiate between different forms of the disease

  5. Explain how to diagnose, treat and prevent plague

  6. Discuss the evolution of the pathogen that causes plague
• Yersinia pestis


  • Rod-shaped bacteria of the family Enterobacteriaceae
  • Gram-negative bacteria
  • Facultative anaerobes, i.e. they are capable of surviving in both aerobic and anaerobic environments
• Xenopsylla cheopis


  The Oriental rat flea
• Life Cycle of Yersinia pestis

  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

  • 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)
  • Black rat (Rattus rattus)
• Flea


  The link between wild and domestic rodents is usually the flea - the rat flea (Xenopsylla cheopis) is the most important vector
• Insect vector


  • 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
• Factors affecting vector efficiency

  • Insect immunity - e.g. antimicrobial peptides
  • Midgut digestive enzymes - pathogen must evade these
  • Frequency of feeding and defecation - pathogen must avoid being removed from the vector
  • Flea life span after infection - pathogen must not kill vector (too quickly!)
• Transmission by the flea

  1. Vectors become infected following uptake of a blood meal, then the pathogen replicates and disseminates in the vector

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

  3. Y. pestis does not adhere to, or invade, the midgut epithelium and so it is potentially susceptible to elimination in flea faeces

  4. Y. pestis persistence in the flea depends on (i) formation of multicellular aggregates (too large to be passed in faeces) AND (ii) their ability to form a biofilm and which creates a blockage in the proventriculus - a valve that connects the oesophagus and midgut

  5. As the biofilm grows, it fills the lumen and when the flea tries to feed it impedes blood flow into midgut

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


  • Highly pathogenic in humans
  • Pathogenicity results from the ability to overcome host defences and multiply within the body - (mainly) extracellularly
  • Following inoculation, Y. pestis induces a local lesion and inflammation - followed by rapid spread and multiplication
  • It is the toxins produced by Yersinia that causes most of the harm - endothelial damage and necrosis - leading to vascular destruction and local haemorrhaging
  • Infection results in the accumulation of neutrophils - Early in infection Y. pestis may be killed by neutrophils, however as Yp is surrounded by the F1 capsule protein, phagocytosis by neutrophils is prevented. Later in infection Yp injects effector proteins (Yops) into Ns killing/disabling them
  • Macrophages can phagocytose Y. pestis but cannot kill it - bacterial toxins can destroy macrophages and other phagocytic cells
  • Lesions result from destruction of tissue and effects of endotoxins - peripheral vascular collapse and disseminated intravascular coagulation (DIC)
• Three (major) recorded plague pandemics through history

  • 541 - The Justinianic Plague
  • 1347 - 'Black Death'
  • 1894 - Modern Plague
• Pandemic


  Prevalent throughout entire country, continent, or whole world
• Epidemic


  Over a large area
• 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 plague pandemics 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
• Deadliest Plagues


  • Justinianic Plague ca 541-549AD
  • Medieval Plague 1347-1352
  • COVID-19 2019-20??
• The COVID-19 pandemic was not as deadly as the historical plague pandemics, with much lower case fatality rates (0.04% to 18.85%)
• Plague is not confined to the history books - animal plague is found in most continents and there is always a risk of human plague wherever the natural cycle (bacterium, animal reservoir and vector) exists in proximity with human populations
• Between 2010-2015, there were 3248 cases of plague reported worldwide, including 584 deaths
• Palaeogenetic research has shown that ancient plague was not the same as more recent plague - the disease is constantly evolving
• The use of plague as a bioweapon is not a new concept - during the 14th century there are reports of attacking armies hurling bodies of deceased plague victims into besieged cities
• In 1970, WHO published a report that estimated 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
• Forms of plague


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


  1. Incubation period 2-4 days - but may be as long as 10 days

  2. Patients often develop 'flu-like' symptoms – sudden onset of fever, chills, head and body-aches, weakness, vomiting and nausea – prodromal period of infection
• Bubonic plague


  • The most common form of the disease, usually initiated by infected flea bite
  • Bacteria enter body and multiply at site of entry in skin - then spreads via the lymphatic system to lymph nodes
  • Lymph nodes become painful and enlarged - forming buboes (Medieval Latin - bubo = swelling – hence the name 'bubonic' plague) with haemorrhagic inflammation 2-6 days after flea bite
  • Onset of fever is abrupt and often accompanied by chills - infected people can become delirious and confused
  • At more advanced stages of infection, buboes may suppurate i.e. burst to form open sores
  • Mortality rate (if untreated) is 50-60% - but if infected person recovers, they are immune to further infection
• Septicaemic plague (Black Death)

  • Septicaemia (blood poisoning) occurs when infection spreads to bloodstream
  • Can result from flea bites and also from direct contact with infective material (e.g. skinning infected wild animals) – primary septicaemic plague
  • Bubonic plague can also develop into secondary septicaemic plague
  • Bloodstream infection - meningitis, endotoxic shock and disseminated intravascular coagulation (DIC)
  • DIC - systemic activation of blood coagulation leads to gangrene of the extremities (Black Death) and multi-organ failure
  • Mortality (if untreated) – 100%
• Pneumonic plague


  • Least common, but most virulent form of the disease (case-fatality 100%)
  • Typically caused by infection spreading to lungs in advanced bubonic plague, but can also result from direct inhalation of infectious droplets
• Microscopic examination of lung tissue showing haemorrhaging, suppuration (pus forming), necrosis, and enormous numbers of bacilli in alveoli
• Infected lung from patient with primary pneumonic plague - showing necrotic nodules and intense haemorrhaging
• 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


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