Historical Pandemics Lecture PDF

Historical Pandemics Pandemic disease = the rapid spread of a disease to many people across multiple continents This lecture focuses on pandemics, but every Epidemic disease = the rapid spread of a p...

Historical Pandemics Pandemic disease = the rapid spread of a disease to many people across multiple continents This lecture focuses on pandemics, but every Epidemic disease = the rapid spread of a pandemic starts as an disease to many people in a certain region epidemic. Endemic disease = A disease that is maintained in a region at predictable levels for long periods of time  How many pandemics in recorded history? Using our definition of pandemic, there have been dozens in recorded human history. In this lecture, we’ll focus on five. In chronological order of origin: First plague pandemic, 541 – 767AD Smallpox pandemic, ≈ 7th century – 1977 Second plague pandemic, 1346 – late 18th century Spanish Influenza pandemic, 1917 – 1920 AIDS pandemic, 1970s – early 2000s. *Note: start dates are not necessarily when the disease emerged in humans. Some diseases circulated at low levels for many years and then turned into a pandemic. End dates are not when disease disappeared but instead when the disease became endemic, which is somewhat ambiguous.  Plague Background What is the “plague”? Plague refers to three different diseases all caused by the bacterium Yersinia pestis. Bubonic plague (lymphatic system infection) Septicemic plague (circulatory system infection) Pneumonic plague (lung infection) The type of plague that develops (i.e., system that becomes infected) depends on the transmission mode and portal of entry into the body.  Plague background – Bubonic Plague The infected lymph nodes become inflamed and swollen, forming the characteristic painful swellings called "buboes," often seen in the groin, armpits, or neck. Extreme nausea, diarrhea and migraine are common. Death comes from infection spreading to internal organs (e.g., spleen, liver). 50% infection fatality ratio if untreated  Plague background – Septicemic Plague Caused by circulatory system infection. Signs and symptoms include vomiting, diarrhea, blood from mouth/nose, tissue necrosis especially of fingers and toes due to disrupted blood flow. Nearly always fatal if untreated  Plague background – Pneumonic plague Caused by infection of the lungs. Leads to very severe pneumonia, including air sacs filling with blood and lung tissue becoming necrotic. Death comes from respiratory failure. Nearly always fatal if untreated Lungs from fatal case of pneumonic plague, showing lesions and necrotic nodules.  Plague Background --Transmission Yersinia pestis has multiple transmission modes: 1) Biological vector (fleas) Reservoir species = wild and domestic rodents 2) Droplets 3) Fomite or direct contact (entry into open wound)  Transmission and Plague Type Infection through flea bite leads to bubonic plague, which can progress into septicemic plague or pneumonic plague Pneumonic plague is contagious (infectious droplets) Infection through respiratory droplets from a human with pneumonic plague leads to pneumonic plague Infection through open wound leads to septicemic plague Small percent that These humans develop pneumonic Droplet would develop plague transmission pneumonic plague *Pneumonic Human would develop bubonic symptoms plague after flea bite, sometimes progressing to septicemic and/or  The First Plague Pandemic When and Where  541 – 767 AD The pandemic consists of a series of 20 plague waves (individual epidemics) beginning with the Plague of Justinian, including Plague of Francia, Rome, among others. Mediterranean Basin, Northern Europe and West Asia hit hardest Plague seemed to follow trade routes; it was probably carried from city to city by rodents Origin  Probably NE India or China First large cities hit were in the southeastern Mediterranean Existed in natural reservoirs (ex: marmots) for many thousands of years.  The First Plague Pandemic Disease Burden: Vast majority of deaths occurred during Justinian wave (541-549). The number of dead is lower than once thought. Current estimates are in the It was once believed that first plague range of 1-5 million deaths (0.5% - pandemic caused fall of Rome. This is unlikely based on revised mortality 2.7% global population at time). estimates. For context, SARS-CoV-2 killed ≈ 0.25% of global population in 3 years  Smallpox Pandemic Caused by Variola major and Variola minor viruses Spread through aerosols, droplets, direct contact and fomites. Extremely durable and long-lived in environment. Disease  at first flu-like (fever, chills, aches) then progresses to visible, rupturing skin lesions, finally multiple organ failure. Most survivors often have noticeable scarring Variola major virus (predominant variant): 10-30% IFR. Variola minor much less virulent Smallpox Pandemic Origin and Timeline of Spread Virus was present in humans at least 3,500 years ago. Became endemic in Africa & India for 2,000 years minimum Starting spreading rapidly during 7th century (beginning of “smallpox pandemic”) Killed 1/3 of Japan’s population in first half of 7th century Smallpox Pandemic Over the following centuries, continued to spread across the world 19th and 20th century saw vaccination dramatically reduce number of cases, deaths. Eradicated in 1977 BECAUSE OF VACCINATION (never became endemic, so this is also when the pandemic ended). Death toll: Estimated 300 million deaths Antivaccine movements contributed to increased deaths in certain in the past 150 years. Difficult to estimate nations before that. The Second Plague Pandemic Same pathogen species (Yersinia pestis) as First Plague Pandemic. However, it was a different lineage. When and Where Pandemic from 1346 to late 1700s. It started with the Black Death in Eurasia and Africa (1346 to 1353) and continued through a series of waves over the subsequent centuries. The Second Plague Pandemic Origin  Culprit strain can be traced to either central Asia or Crimea. War, trade, and travel throughout Europe, Asia, and Africa all likely facilitated the spread and outbreaks. Second Plague Pandemic: Black Death Wave Disease Burden: Most deaths during the second plague pandemic occurred during the first and most notorious plague wave -- Black death (1346 – 1353) 75–200 million deaths worldwide 17-55% loss of global population, 30-60% European population 5-6% global population killed/year Context: that is equivalent to 400-500 million deaths per year with today’s population. In terms of proportion of global population Estimated European killed, The Black Death wave was the deadliest population over time. Took more than two centuries to event in human history. recover.  Spanish Influenza Pandemic Caused by H1N1 influenza A virus Current evidence suggests Avian influenza origin. Intermediate host – unsure Reconstructed virus shows high degree genetic similarity to avian influenza viruses Why so severe? Genetically more virulent than previous and current influenza viruses Kills mice and chicken embryos in lab (unusual) Replicates in wide range of cells (expanded tissue tropism) Not dependent on usual host cell receptor to facilitate cellular entry No acquired immunity in humans The Spanish Flu https://www.youtube.com/watch?v=3x1aLAw_xkY Spanish Flu: a warning from history - YouTube  Spanish Influenza Pandemic When and Where –> 1917 – 1920 Spread in multiple waves across the 2-3 years What happened to it? Still around. Became endemic “seasonal” influenza. Evolved to be less virulent plus increased levels of acquired immunity. Seasona l flu  Spanish Influenza Pandemic Origins No concrete evidence on origins, but not from Spain (misnomer) Best evidence we have comes from historical documents – competing hypotheses for United States (Kansas), Europe and China origins Disease burden: 50 to 100 million deaths across 2.5 years (1917- 1920) Highest mortality in young adults. Why? Overreactive immune system (Cytokine storm) High rate of secondary infections (war conditions) AIDS Pandemic Caused by Human Immunodeficiency virus (HIV-1) HIV-1 Origin: Pandemic virus emerged in humans sometime between 1910-1930 (this is not when pandemic began). Africa (Kinshasa, Congo) – Simian Immunodeficiency Virus (SIV) of chimpanzees made its way into humans through blood-blood contact (probably hunting). HIV-1 spilled over into humans on three separate occasions. HIV-1 clades M, N, O, which currently circulate in humans, do not share a common ancestor in humans. Clade M HIV-1 Spread Pandemic began in 1970s: By this time, HIV-1 had spread to several continents, including North America Cryptic transmission and prolonged disease manifestation helped virus spread undetected for years. HIV came to United States from Haiti HIV was already global by the time AIDS was officially recognized as a disease. HIV-2 also circulates in humans. It makes up only 10% of HIV infections, nearly all of which are in west Africa. HIV-2 is not considered a cause of the AIDS pandemic (but it did cause an epidemic in Africa after its emergence). HIV-2 spilled over into humans directly from Sooty mangabey, probably in the 1940s or 1950s. AIDS Pandemic AIDS Pandemic Death Toll Estimated 35-40 million deaths worldwide since 1980 Nearly all HIV-1 infections eventually cause AIDS if untreated AIDS is 100% fatal Deaths have been dramatically reduced due to antiviral drugs  For Thursday Last exercise of semester Download Plague Inc. on mobile device or laptop from app store ($0.99). Alternative assignment for those who wish to opt out.