(B) Lecture 12: The Black Death Flashcards
Yersinia
- Gram NEGATIVE
- rod shaped bacterium
3 species are pathogenic for humans:
- Y. enterocolitica: causes diarrhea + ab pain
- Y. pseudotuberculosis: cause TB-like symptoms
- Y. pestis: cause of plague
What bacterium is responsible for Plague?
Yersinia pestis
Yersinia pestis
- pestis = pestilence (contagious)
- may cause death in 2-4 days by sepsis and/or overwhelming pneumonia
- NOT an effective colonizer of humans = causes death or immune system kills it
Plague
- incubation of 3-7 days
- patients experience sudden onset of fever, chills, headaches, muscle pain, weakness
- painful swelling (BUBOES) of lymph nodes in armpits, legs, neck or groin
- high fever, derilium and mental deterioration, vomiting of lungs
Plague pandemics
- Plague of Justinian (first pandemic)
- The “Black Death” (second pandemic)
- Mid-19th century (third pandemic)
Plague of Justinian
- first epidemic
- named after Roman Emperor
- started in 6th century
- caused by Yersinia pestis
- spread to Mediterranean, Italy and throughout Europe
- approx. 50% of population died
- continued in CYCLES for another 200 years
- estimated to have killed 100M ppl
The “Black Death”
- caused by Yersinia pestis
- originated in Asia and reached Europe
- reduced global population by 100M
- no real treatment - fear turned to panic
- many ppl believed this was due to God’s anger or Satan = persecution of minorities + witches
- European social order, family structure + feudal system were destroyed
- Plague Doctor
Plague Doctor
- beak/plague mask would be filled w/ flowers to “help w/ stench” – actually protected them from microbes
- random ppl would dress up as physicians to make money
Feudal System
- political and social structure prevalent in Europe
- peasants -> knights -> nobles -> king
- little opportunity for advancement
- a few ppl had everything, most had little
- plague infected everyone = made holes in feudal system
- plague created vacant towns/farms + positions of authority needed to be filled
- provided new opportunities for peasants (demand for physicians, clergy)
How did they know that Y. pestis caused the Black Death?
Victims were buried and recorded well
Today, they use teeth + genomic sequencing technology to find Y. pestis
Found that DIFFERENT strains caused the Plague of Justinian and Black Death
The third pandemic
- Mid-19th century
- spread through infected RATS that exchanged fleas w/ local wildlifr
- started in China + spread to all continents
- go to southwestern US
Pathogenesis of Y. pestis
- organisms live in RODENTS + are transmitted by fleas
- a ZOONOTIC pathogen
- causes “blocking” in flea = STARVING fleas (fleas can bite but can’t get bloodmeal = flea is alwas hungry and biting different hosts) - mechanism of transmission
- very LOW infective dose
- Y. pestis initially survives and grows in innate immune cells –> replicates in lymphoid organs
- lymph nodes –> swelling –> buboes
- Kills phagocytes and continues to grow extracellularly
Virulence factors of Y. pestis
- remarkable ability to overcome immune defenses = large growth in vivo
Major virulence factors
- Type III secretion (in gram NEG INTRACELLULAR bacteria)
- Phospholipase (survival in flea)
- Plasminogen activator = clot buster (dissemination: clot-busting allows transmission)
- Yersiniabactin – iron binding siderophore (allows pathogens to get iron to grow)
- LPS structure is ‘mutated’ =innate immune system does not recognize it immediately (only in gram NEG)
Type III Secretions
- found only in gram NEG pathogens (usually INTRACELLULAR)
- molecular syringe that crosses 3 membranes
- secrete virulence factors (effectors) directly into host cells across host cell membrane
- effectors ‘poisons’ host cell by targeting host cell signaling pathways
MOST gram neg bacteria that live in host cells have type III secretion systems
Evolution of Y. pestis
- Y. pestis evolved from Y. pseudotuberculosis
- Y. pestis acquired new virulence PLASMIDS
- all pathogenic Y. pestis contain pYV which encodes type III secretions
- Y. pestis can infect flea and is hypervirulent – survives well in animal intestine
- Y. pestis LPS molecule is weakly recognized by innate immune system due to mutation in LipidA enzyme
Y. pseudotuberculosis
mainly an intestinal pathogen of animals
- found widely in environment
causes TB-like symptoms
Major forms of plague
- Bubonic plague
- Septicemic plague
- Pneumonic plague
Bubonic plague
- most COMMON form
- transmitted by FLEA bites
- painfully swollen lymph nodes (buboes) in groin, armpits and neck
- can develop into septicemic and pneumonic plague
- 40-60% mortality, if untreated
Septicemic plague
- presence of Y. pestis is systemic (in blood)
- an overwhelming and progressive bacteremia (bacteria in blood)
- fleas can pick up Y. pestis to transmit to a new host
- patients experience gangrene and disseminated INTRAVASCULAR COAGULATION
- 50-90% mortality if untreated (higher mortality than bubonic plague)
Pneumonic Plague
- MOST DANGEROUS
- transmitted via aerosols directly into the lung, or spread to lungs from septicemic plague
- short incubation
- disease can pass directly from person-to-person thru coughing (NO VECTOR)
- 95-100% mortality if untreated, but treatment must be within first 24h of symptoms
Transmission of plague
4 routes for human disease:
- FLEA-BITE (MOST COMMON)
- inhalation from humans (pneumonic) or animals
- handling infected animals - skin contact, scratch, bite
- ingesting infected meat
Historically rat-borne
- now mostly wildlife associated plague
Diagnosis, Treatment and Prevention of Plague
- rapid diagnosis + treatment is ESSENTIAL
- in endemic regions, there are stains + rapid antigen tests
- pneumonic patients should be isolated
- insecticides to kill fleas
- appropriate antibiotics including prophylaxis to exposed individuals (treat BEFORE sickness if you think they’re exposed)
Plague as a bioterrorism agent
CDC identifies Plague as a “Category A” organism
- can be easily spread + transmitted from person to person
- high mortality rates
- might cause public panic + social disruption
In 1347, Mongol armies catapulted plague-ridden bodies over the city walls
In WWII, Japanese Army infected fleas and released them in China
Plague currently around the world
Madagacar is a hotspot for plague
- epidemic
No plague in Canada, Australia or Antarctica
