IHS 340 Exam Three

Plague (broad definition)

Any epidemic disease that causes a high rate of mortality in a population.

Plague (microbiological definition)

Any epidemic or pandemic specifically caused by the bacterium Yersinia pestis.

Yersinia pestis

The gram-negative, coccobacillus-shaped bacterium responsible for plague; belongs to the Enterobacteriaceae family; non-motile and a facultative anaerobe.

Coccobacillus

A bacterial shape intermediate between a sphere and a rod — short and oval like a stubby rod.

"Safety pin" morphology

The characteristic staining appearance of Y. pestis where the ends stain darker than the center, resembling a safety pin.

Facultative anaerobe

An organism that can survive and grow with or without oxygen.

Enterobacteriaceae

The bacterial family to which Y. pestis belongs — a large group of gram-negative rods often found in the intestines of animals and humans.

Gram-negative bacterium

A bacterium that does not retain crystal violet stain in the Gram staining process, indicating a thin peptidoglycan layer and an outer membrane.

Xenopsylla cheopis (oriental rat flea)

The primary flea vector responsible for transmitting Y. pestis to humans by feeding on infected rodents and passing the bacteria through its bite.

Reservoir hosts

The main long-term carriers of Y. pestis — primarily rodents (black urban rats, brown sewer rats) and the fleas that feed on them.

Black urban rat

One of the primary flea host rodents that serves as a key reservoir for Y. pestis.

Brown sewer rat

A second primary flea host that also serves as a key reservoir for Y. pestis.

Incubation period

The time between Y. pestis infection and appearance of symptoms — typically 2 to 6 days.

Flea transmission cycle

A flea feeds on an infected rodent, acquires Y. pestis, then transmits it to a human through its bite.

Zoonotic transmission

Transmission of Y. pestis that can also occur when humans handle the tissues or body fluids of a plague-infected animal.

Bubonic plague

The most common plague form; bacteria travel through the lymphatic system to lymph nodes where they replicate, causing swollen painful nodes (buboes), along with fever, chills, headache, and weakness.

Bubo

A swollen, painful lymph node caused by Y. pestis replication inside it — the telltale sign of bubonic plague.

Septicemic plague

Plague where Y. pestis enters the bloodstream, causing subcutaneous hemorrhaging, tissue death, worsening fever, chills, and weakness that can lead to shock. Can be primary or secondary.

Primary septicemic plague

Y. pestis enters the bloodstream directly with no prior bubonic stage — no visible buboes.

Secondary septicemic plague

Y. pestis spreads into the bloodstream from an already-infected lymph node following initial bubonic infection.

Pneumonic plague

Plague targeting the lungs, causing rapid severe pneumonia that can lead to respiratory failure. The only form spread directly person-to-person via respiratory droplets.

Primary pneumonic plague

Caused by directly inhaling Y. pestis — bacteria go straight to the lungs without prior lymphatic involvement.

Secondary pneumonic plague

Occurs when Y. pestis spreads from the bloodstream or lymphatic system into the lungs after initial infection elsewhere.

Target organs — septicemic plague

Spleen, liver, kidneys, skin, and brain.

Target organs — pneumonic plague

The lungs.

Virulence plasmids of Y. pestis

Three plasmids plus a pathogenicity island that together encode the majority of Y. pestis's disease-causing abilities.

Slime layer

A protective coating produced by Y. pestis that shields the bacterium from the host's immune cells.

YopJ toxin

A toxin produced by Y. pestis that lyses (destroys) macrophages, helping the bacteria evade immune defenses.

Pla (protease)

A Y. pestis protease that activates plasmin in the human host, preventing normal blood clotting and helping spread infection.

Siderophore proteins

Proteins encoded by Y. pestis virulence genes that allow the bacterium to scavenge and use iron from the human host for its own growth.

Type III secretion system (T3SS)

A molecular "needle" used by Y. pestis to inject toxic proteins (Yops) directly through the host cell membrane into the cytoplasm.

Yersinia outer proteins (Yops)

Toxic effector proteins injected into host cells via the T3SS; once inside, they trigger apoptosis.

Injectisome

The protein structure forming the injection apparatus of the T3SS.

Translocon proteins

Proteins that form a pore in the host cell membrane through which Yop effectors are delivered.

Apoptosis (in plague context)

Programmed cell death triggered inside host immune cells by Y. pestis Yop effectors, destroying the immune response.

Alexandre Yersin

French bacteriologist sent by Pasteur to Hong Kong who identified Y. pestis by studying buboes from plague victims; the bacterium is named in his honor.

Kitasato Shibasaburō

Japanese bacteriologist sent by Koch to investigate plague; failed to confirm the plague agent from samples taken from a deceased sailor.

Plague doctor (17th century Europe)

Physicians who wore a beak mask filled with aromatic plants, gloves, goggles, a coat, and carried canes to maintain distance from patients — incidentally providing real protection against airborne transmission.

Beak mask

Worn by plague doctors and filled with aromatic plants — intended to purify air per miasma theory, but incidentally acted as a primitive respiratory barrier.

Why was the Black Death so devastating?

Not due to exceptional virulence genes in Y. pestis, but likely a combination of extremely unsanitary medieval living conditions and co-occurring infections that weakened host immunity.

Plague pits

Mass burial sites from plague outbreaks being studied today; researchers sequence ancient Y. pestis DNA from remains to investigate historic devastation.

Diagnosis of plague

Based on patient travel history to endemic areas, clinical signs (buboes), microscopy, and bacterial culture.

IV antibiotic course

Standard modern plague treatment — intravenous antibiotics for 10 to 14 days.

Levofloxacin

FDA-approved fluoroquinolone antibiotic for treating plague in the U.S.

Moxifloxacin

Second FDA-approved fluoroquinolone antibiotic for treating plague in the U.S.

Streptomycin

An antibiotic effective against Y. pestis; not FDA-approved specifically for plague but still used.

Chloramphenicol

An antibiotic effective against plague; some resistance has emerged in certain strains.

Tetracycline

An antibiotic effective against Y. pestis; antibiotic resistance in some strains has been documented.

Antibiotic resistance in Y. pestis

Some strains have begun showing resistance to streptomycin, chloramphenicol, and tetracycline — an emerging concern.

Plague vaccine

A vaccine exists but the CDC only recommends it for individuals with high occupational exposure to Y. pestis.

Sanitation as plague control

The most important public health measure — reducing rodent and flea populations limits the disease's spread to humans.

Current U.S. plague burden

An average of 7 cases per year; still endemic at low levels in the western U.S.

Last U.S. urban rat-associated outbreak

Los Angeles, California, 1924-1925.

Sylvatic plague

Plague circulating in wild rodent populations; can have over 90% mortality in affected rodents, disrupting ecosystems.

Spillover risk

The concern that Y. pestis in wild rodent populations could spread into human populations — active monitoring and prevention measures are taken.

Ecological impact of sylvatic plague

High rodent mortality disrupts food webs and ecosystems, affecting predators and habitat balance.

Global plague distribution today

Low-level endemic plague still exists in parts of North and South America, Africa, and Central Asia.

Non-Infectious Microbial Disease

A type of infection caused by microbes (parasites, soil microbes, non-domestic animal reservoirs, etc.) that are always around; the immune system evolved to defend against them — not transmissible between people

Infectious Disease

A transmissible (contagious) disease that required major societal changes to emerge — such as agriculture, domestication of animals, cities, and trade routes — and has been a major force of historical change

Epidemic

When a new population encounters a new pathogen, resulting in devastating, widespread, sudden mortality

Endemic

The stable state of a disease after an epidemic — the disease becomes routine, affecting mostly the young or causing regular but minor mortality rather than societal collapse

Global Equilibrium Model (McNeill, 1976)

William McNeill's model describing the long-term ecological balance achieved between human populations and pathogenic microorganisms, where infections become endemic rather than causing massive sudden mortality

Equilibrium Requirement (McNeill)

Societies survive and thrive only when the disease environment and the political control environment are both in balance with each other — both can sap energy from the population when out of control

Disruption of Equilibrium (McNeill)

The Global Equilibrium is shattered when distinct disease pools (separated geographic regions) are brought into contact (e.g., via the Silk Roads, Mongol conquests, or Columbian Exchange), exposing "naïve" immune systems to unfamiliar, virulent pathogens

Naïve Immune System

An immune system with no prior exposure or immunity to a particular pathogen, making a population extremely vulnerable to that disease

Crowd Diseases

Infectious diseases (e.g., smallpox, measles, influenza) that evolved because of dense urban living and agriculture; require large, concentrated populations to persist

Zoonoses

Diseases that originated from domesticated animals and jumped to humans (e.g., measles from cattle, influenza from pigs/ducks)

Fecal-Water-Oral Transmission

A route of disease transmission where infected feces contaminate water or food that is then consumed — increased by sedentary (farming) lifestyles

Why Agriculture Enabled Epidemic Disease (Density)

Agriculture sustains 10-100x higher human population density than hunter-gathering, concentrating people and increasing disease spread

Why Agriculture Enabled Epidemic Disease (Sanitation)

Farmers are sedentary and live among their sewage, increasing fecal-water-oral transmission; hunter-gatherers frequently move camps and leave infected feces behind

Why Agriculture Enabled Epidemic Disease (Rodents)

Sedentary farming populations attract rodent populations, which serve as disease reservoirs (e.g., rats and bubonic plague)

Why Agriculture Enabled Epidemic Disease (Mosquitoes)

Deforestation for farming provides breeding grounds for mosquitoes, enabling diseases like malaria

Why Agriculture Enabled Epidemic Disease (Cities & Trade)

Higher population density led to cities with even worse sanitation; cities became market centers that gave rise to trade routes, spreading infectious diseases globally

Self-Sustaining Urban Populations

It was not until the 20th century that Europe's urban populations became self-sustaining — before that, constant immigration of healthy rural peasants was needed to replace city dwellers who constantly died from "crowd diseases"

Measles (Animal Origin)

Derived from cattle (rinderpest virus)

Tuberculosis (Animal Origin)

Derived from cattle

Smallpox (Animal Origin)

Derived from cattle (cowpox) and other livestock with related pox viruses

Influenza (Animal Origin)

Derived from pigs and ducks

Bubonic Plague (Animal Origin)

Associated with rats (not domesticated by human choice)

Population Threshold for Measles Persistence

Measles is likely to die out in any region-confined human population under 500,000 — because the birth rate does not exceed the disease transmission and recovery rate

Faroe Islands Measles Example (1781-1846)

A measles epidemic reached the Atlantic island of Faroe in 1781 and then died out; the island was measles-free 1782-1846; in 1846, an infected carpenter from Denmark arrived and infected the entire population of 7,782 within three months; measles was gone again by 1847 — demonstrating how naïve populations are devastated by reintroduction

Equatorial Migration Model

McNeill's model describing how the evolution of human infectious diseases is a history of humans "escaping" and then "reconnecting" with tropical disease pools

Tropical Reservoirs

Tropical and equatorial regions serve as the original "hothouses" of disease; because they support high biodiversity, they harbor vast arrays of pathogens and parasites that co-evolved with early human ancestors

Temperate Migration and "Release"

As humans migrated out of Africa into temperate climates, they temporarily left many tropical diseases behind, allowing for rapid population growth in cooler regions where many tropical parasites could not survive winters

Equatorial-to-Temperate Diffusion

As civilizations expanded and trade routes (like the Silk Road) opened, diseases endemic in one region (often humid tropics) migrated to novel, vulnerable populations in temperate zones — frequently causing devastating "virgin soil" epidemics

Virgin Soil Epidemic

An epidemic that occurs when a disease is introduced to a population with no prior immunity — resulting in extremely high death rates (often 90%+)

Pathogen Attenuation (McNeill)

Over time, the most lethal new diseases tend to evolve toward a more stable, endemic relationship with their hosts — becoming less deadly as the population develops collective immunity

Parasite Load

The basal infection rate of a region — higher near the equator (warm, moist) and lower in cold, dry climates; the equatorial regions have a high parasite load

Parasite (McNeill's Definition)

A microorganism capable of infecting a warm-blooded host

Hippocrates (460-377 BCE)

Ancient Greek physician who recorded some of the earliest documented descriptions of infectious diseases

Diseases Recorded by Hippocrates

Mumps (epidemic on island of Thasos), Malaria (3- and 4-day fevers), Diphtheria, Tuberculosis, Influenza

Diseases NOT Seen by Hippocrates

Smallpox, Measles, Bubonic plague — these had not yet emerged in the populations Hippocrates encountered

Plague of Athens

A devastating epidemic that struck Athens in 430 BCE during the height of Athenian power, killing 33-67% of the population, destroying much of the navy, and causing societal collapse — contributing to Athens' eventual defeat in the Peloponnesian War

Peloponnesian War Context

The plague struck during the 431-404 BCE war between Athens and Sparta; Athens was initially winning but the epidemic prevented a decisive blow, dragging the war on for 27 years until Athens' defeat

Symptoms of the Plague of Athens

Rapid onset, raging fever, extreme thirst, red splotches on skin, skin pustules and ulcers, bloody tongue and throat; affected all classes and disproportionately killed physicians

Pathogen of the Plague of Athens

Unknown — symptoms do not match any known disease; possible causes include smallpox, pneumonic plague, scarlet fever, typhus, measles, or a long-since-disappeared pathogen

Thucydides

Ancient Greek historian (born ~460 BCE) who wrote "History of the Peloponnesian War," the only surviving source for much of the period — he personally witnessed and documented the Plague of Athens

Emperor Justinian

Byzantine (Eastern Roman) Emperor who campaigned to re-establish a united Roman Empire, erected magnificent buildings, and established the Justinian Code of Laws (basis of European justice for many years)

Justinian Plague (542 CE)

Considered possibly the worst plague to ever ravage the world — first appeared in 540 CE; killed up to 10,000 people per day at its peak in Constantinople

Causative Agent of Justinian Plague

Predominantly bubonic plague (Yersinia pestis); spread from lower Egypt up through Palestine and throughout the rest of the world