Bio Anthro

Paleopathology

investigation of diseases and related condition from skeletal and soft tissue remains • only possible for a small subset of pathogens • and difficult to distinguish for sure on very old samples even for those

Dealing with symptoms

many societies have had many ways to approach this - common themes among traditional approaches include: » applying heat or cold » consuming herbs or spices » use of water » eliminating substances from body (bleeding, emetics, etc.) - common themes among traditional understandings of cause: » humors » forces » imbalance

Harden

"HIV has spread rapidly in geographic locations where individuals engage in sexual relations with many partners" Very simple statement of something that is much more complex - Clear now that "many partners" are not necessary to maintain HIV epidemic

Smallpox eradication

"High point" of global health • Decision to focus on eradication made in 1959, based on: Severity of the disease Direct transmission No asymptomatic carriers No animal reservoirs Inability to live outside body long Lifelong immunity for survivors Single-dose vaccine with lifelong immunity Unprecedented coordination among international community • 1967 - switched from mass vaccination to ring vaccination Generated occasional tragedies - 1972 Yugoslavia outbreak • 175 cases, 35 deaths • 18 million vaccinations within a month • By 1975 - reduced to Bangladesh, Ethiopia and Somal

Big three fundamental shifts:

1. Increased group sizes 2. Sedentism and sanitation 3. Proximity to livestock

But - three very important (and interrelated) issues arise when doing so

1. Names of diseases in old texts are often very general e.g. "plague" - any infectious disease e.g "leper" - someone suffering from any skin disease e.g "pox" - any disease with pustules - In large part because they are only based on a few major symptoms, with no knowledge of the pathobiology (obviously) 2. Translation of disease names from one language to another can be difficult to impossible e.g "aaa" 3. Pathogens have evolved, and symptoms and severity change - general pattern: severity is high at first, and then declines - why? • E.g. measles was initially considered the same disease as smallpox - Abu Bakr al-Razi (Rhazes) first to distinguish them c. 890 CE - Likely was evolvingto be less virulent

China

1200: Under the Song Dynasty, China is the largest and wealthiest nation on Earth - population estimates exceed 100 million • 1271: China becomes a vassal state of the Mongol Empire, under the Yuan Dynasty • 1330s: Outbreak of something occurs, focused in Hebei Province (around modern-day Beijing) • Various second-hand sources (from later or from elsewhere) suggest mortality of 50-90% • But give little additional detail • 1393 census: population of China is ~65 million

Quarantine

1377: The Italian republic of Ragusa (now in Croatia) begins to require visiting ships to spend 30 days in isolation before coming ashore • 1387: Venice adopts the policy, but extends it to 40 days Number comes from a statement by Hippocrates that all plagues have an incubation period up to that length Lazaretto: maritime quarantine station • Philadelphia Lazaretto • With time - quarantine moves from potentially infected ships to new forms Infected communities Potentially infected individuals Infected individuals

1492

1492: arrival of Europeans in the Caribbean • Epidemics started immediately, including smallpox, measles, influenza, tuberculosis, pertussis • Effect was perhaps the greatest demographic and cultural disaster in human history Death of perhaps 40-90 million people Paving the way for the decimation of hundreds of distinct cultures and languages and ways of life Indigenous people living in Hispaniola in 1492 were the Taino • Estimates for their population size range widely, but concentrate around 500k - 1m • 80-90% were killed by infectious disease within a generation • Many of the rest were killed by Spanish violence, the hardships of slavery, and famine There were 60,000 people living on this island [in 1508], including the Indians; so that from 1494 to 1508, over three million people had perished from war, slavery and the mines. Who in future generations will believe this? None of this was unique to the Spanish • E.g. The Native populations of coastal New England suffered a severe epidemic, 1616-1619 The Pilgrims at Plymouth Colony, 1620 Report abandoned villages and farms throughout the region

Smallpox in the Western Hemisphere

1517 - outbreak among African slaves in Hispaniola - spread to native population • 1518 - outbreak in Cuba • 1519 - outbreak in Puerto Rico • 1520: spreads to the Aztec Empire in Mexico continues into Central America and Yucatan • 1524: spreads to the Incan Empire in Peru

The rise of germ theory

1546: Girolamo Fracostori proposes that epidemic disease are caused by tiny particles called "spores" Hypothesizes both direct and indirect transmission, including fomites • 1670s: Anton van Leeuwonhoek invents microscope, observes bacteria • 1840s: Second Cholera Pandemic is raging in the slums of London Aug 31, 1854: highly localized outbreak hits SoHo: • 127 people die within 3 days • 500 more over the next month John Snow interviews residents the pattern of disease Almost all got their water from the Broad St pump

Subsequent smallpox epidemics

1770s (throughout region) • 1801-2 (in and around Washington and Southern BC) • 1836-8 (in Alaska, Northern BC and Oregon; skips Washington and Southern BC) • 1853 (in and around Washington) • 1862-3 (in and around Southern BC) • Susceptible replenishment shaping (and taking) generations of lives and societies • Interspersed with other major outbreaks of influenza, tuberculosis, measles, dysentery, meningitis, and mumps

Characteristics making a pathogen more likely to persist in hunter-gatherers: 3

3. It can survive for long periods of time outside the human body tetanus • waterborne and soilborne, via feces • usually transmitted via puncture wound

Characteristics making a pathogen more likely to persist in hunter-gatherers: 4

4. It has a natural animal host sufficient to keep it going, and only infects humans as a secondary host •East African trypanosomiasis (T. brucei rhodesiense) •Resides in multiple mammal species T. brucei rhodesiense is only one gene different from T. brucei brucei T.b.b. only infects game animals T.b.r. infects game animals and humans Reasonable that T.b.r evolved from T.b.b. and affected hunter-gatherers on the African savannah rabies • transmitted to humans via animal bite botulism • usually transmitted via uncooked food • Releases botulism toxin but none can keep human infection chains going on their own Often called "souvenir" pathogens

KNM-ER 1808

A 1.7 million-old female Homo erectus skeleton found in Kenya Possesses severe pathology One group of researchers believes these are most consistent with a case of yaws Most now believe it to be an excess of vitamin A Other cases of pre-agriculture paleopathology are similarly ambiguous • Absence of evidence alone does not equal the evidence of absence!

Plague of Justinian (541-542)

Analyzed teeth from mass burials dating to the right time period in Southern Germany • Discovered a new variant of Y. pestis • On a side branch of the tree with no descendants Previously known versions of pathogenic Y. pestis Already seen in terms of the Plague of Justinian Which happened earlier in time, but the genetic discoveries came later • For Second Plague Pandemic, the genetic research was truly groundbreaking Occurred in the face of growing argument that something other than Y. pestis had caused the Black Death, based on: • Speed of symptoms • High mortality • Geographic distribution 14th century Y. pestis specimen from London matches the expected pattern for the ancestral node of present-day Y pestis variations • Does not contain any major alleles that don't appear in present-day versions • So, may not have been fundamentally different in its virulence or symptoms • Subsequent analyses with additional samples suggest two separate entries into Europe during the 2nd pandemic

Antonine Plague (165-180)

Antonine Plague (165-180) 20 • Crawford again suggests major role in the decline of the Roman Empire • But historians are much more mixed on this on • Scholars have again debated its cause endlessly • Thanks to the narrower set of symptoms described in more detail, range of possibilities is smaller: Smallpox Measles Typhus • No paleopathological or genetic evidence First appears in documents among Roman troops attacking Seleucia (present-day Iraq) • Brought back to Rome by troops • Symptoms documented by the physician Galen Began with fever, diarrhea, sore throat Then skin rash / pustules around Day 9 • 2,000 people died in one day in Rome alone • Estimated to kill 5 million people in multiple waves out of a total population of 60 million in the whole empire • Roman army devastated • Historians record a major rise in religiosity • "Barbarian" troops allowed into Army

Plague of Justinian (541-542)

At this time, the Byzantine Empire had replaced the Roman Empire • Probably brought into Constantinople on a trading vessel • Recorded by historian Procopius • Symptoms included black swellings (buboes) and necrosis • Deaths numbered ~25 million in first outbreak • Reappeared for centuries, with many more deaths • Society, economy, political structures all devastated Long believed to be caused by Bubonic plague (Yersinia pestis) • However, scientists began to question this in the 2000s - genetic variation in known Y. pestis made it seem to be more recent • Analyzed teeth from mass burials dating to the right time period in Southern Germany • Discovered a new variant of Y. pestis • On a side branch of the tree with no descendants

Reaction

Attempt cure "in-gathering" with shaman sweat-bath / cold-bath • Grieve "He himself had lost ten children by it; he had ten strokes tattooed on one of his arms, which I understood were marks for the number of children he had lost." • Determine cause As punishment - "The Tlingit supposed that this illness was visited on them by the [raven] as a punishment for the endless wars they waged among themselves." From Europeans: "the Spaniards, as the natives say, brought it among them." • Consolidate tribes "An epidemic almost exterminated the Hoyalas, and the remnant scattered among the tribes to the south and on the eastern coast of Vancouver Island, where they had relatives by marriage." • Take over newly emptied lands "When the smallpox wiped out a tribe on Boundary Bay, the Semiahmoo took over their territory."

Third Bubonic Plague Pandemic

Began in southern China in the 1850s • Re-emerged in Hong Kong and nearby in the 1890s • Spread to India also in the 1890s • Only declared over in 1945 in Argentina • 12-15 million dead (mostly India) Hawaii annexed by the US in 1898 • Small plague outbreak in Honolulu's Chinatown in 1899 • At this point: Bacillus is identified Connections with poverty and poor living conditions recognized Specific connection with rats now generally understood, although not officially proven until 1905 Authorities invoke "cordon sanitaire", prevent residents from leaving Various sanitation methods imposed "Plague lives and breeds in filth and when it got to Chinatown, it found its natural habitat." —Dr. C. B. Wood, Board of Health, Territory of Hawai'i Homes of victims purposefully burnt Neighborhood accidentally (?) set on fire January 30, 1900 Ship arrives from Japan via Honolulu to Port Townsend, Washington 17 cases of bubonic plague on board, 3 deaths Ship and crew quarantined Undergo repeated forms of disinfection Plague does not spread West Coast authorities start to freak out San Francisco Examiner published front page article "Why San Francisco is Plague Proof" S.S. Australia arrives from Honolulu to San Francisco in January • Passengers and crew checked for plague, pass inspection • In February, a Chinese-American lumberman named Wong Chut King falls ill, dies after 4 weeks • Police coroner sees buboes, informs health department; they inform Chief Kinyoun, medical inspector at Angel Island who confirms with lab tests • Mar 7, 1900: city's Board of Health places cordon sanitaire around 12 city blocks of Chinatown (30,000 residents) • Residents of Chinatown, and Chinese consulate protest • Mayor resists, saying community was "a constant menace to the public health." • Nevertheless, quarantine lifted after 2 days, replaced with disinfection process • Additional cases begin appearing in Chinatown Governor Henry Gage - worried about the financial impact - publicly insists that there is no plague in San Francisco • Multiple newspapers agree • Backed by railroad executives, they begin intense smear campaign against Kinyoun • Federal government investigates, determines plague is present • Gage condemns new report • US Surgeon General calls for: Re-quarantine Mass immunization of all Asians and Asian-Americans with experimental vaccine • Chinese community files class-action lawsuit • Federal judge rules in favor of Chinese community 1901: Epidemic grows • Gage and newspapers expand smear campaigns but become increasingly marginalized • States begin to impose boycotts on all California goods • 1902: Gage loses re-election • New governor is a physician - works with federal authorities to re-institute sanitation and disinfection processes • Plague quickly comes under control • 200 deaths had occurred

Vaccination

Beyond the science, mandatory vaccination laws and their exemptions raise complex ethical and legal issues regarding: The balance between individual freedom and community safety The state's role in determining and enforcing that balance The boundary of religious freedom The definition of religion vs personal belief The role of the state in evaluating religious tenets The role of the state in determining if/when a parent is not adequately protecting the safety and well-being of their child

Cultural reaction

Blame Jewish community Accused of creating it and/or purposefully spreading it to others Began in Toulon, France in 1348 - Jewish neighborhood attacked, 40 killed Quickly spread Pope Clement VI attempted to stop with two Papal Bulls Reached high point with the Massacres of Erfurt and Strasbourg, 1349 Hundreds of Jewish communities destroyed Heightened religiosity Flagellant movement • Reduced religiosity Driven by failure of Church to provide real help Decameron by Bocaccio Artist obsessions with death and fate

Smallpox Blankets

British takes area around modern-day Pittsburgh from French, 1763 • Native tribes in area unhappy, rebel • Settlers take refuge in Ft. Pitt, natives lay siege to fort • General Jeffery Amherst writes to Colonel Henry Bouquet: "Could it not be contrived to Send the Small Pox among those Disaffected Tribes of Indians? We must, on this occasion, Use Every Stratagem in our power to Reduce them." • Bouquet replies: "I will try to inoculate the Indians by means of Blankets that may fall in their hands, taking care however not to get the disease myself" • Commander writes in diary: "Out of our regard to them we gave them two Blankets and an Handkerchief out of the Small Pox Hospital. I hope it will have the desired effect."

HIV resistance

CCR5Δ32 allele of the CCR5 gene - discovered in 1996 • Homozygotes are almost entirely resistant to HIV infection • Heterozygotes have a lowered risk of infection, and delayed progression of disease Early genetic work suggested the allele was around 700 years old, dating it to the 13th century • HIV affects macrophages, just like......bubonic plague • Spatial variation of gene resembles that of spread of plague across Europe in reverse • Hypothesis: CC5Δ32 also provides resistance to bubonic plague • But: Experiments with mice showed that bubonic plague is equally able to infect cells with or without CCR5 Two mass graves (one famine, one plague) from similar time and place have same CCR5 frequencies Next hypothesis: smallpox Proposed due to its role as another major selective force in human history Would have been powerful enough to get the allele up to high frequency in that time frame No tests of the hypothesis have occurred • In the meanwhile, new samples and phylogenetic work suggest the mutation may actually be much older • Stay tuned!

Paleopathology Example

E.g. Treponemal infections Caused by spiral-shaped bacteria of the genus Treponema Include: • syphilis • yaws • pinta • bejel Each yields distinctive markings in the bone E.g. yaws: • ulcerative lesions in the nasal cavity and the soft palate • bending of the tibia (leg bone) • additional lesions on bones http://www.who.int/mediacentr

Basic Biology and life cycle (black death)

Caused by the bacillus (rod-shaped bacterium) Yersinia pestis • Spread among hosts by a variety of flea species, e.g. the Oriental rat flea (Xenopsylla cheopis) • Most common hosts are various rodents: Rats (especially the Black rat and the Brown rat) Marmots Prairie dogs • Flea can also bite human host Fleas: bacterium replicates heavily • Blocks the proventriculus • Causes blood "backwash" on future feedings With a flea bite, bacterium bypasses skin • Has a type of adhesin protein on its cell surface that allows it to adhere to and enter epithelial cells • Releases a host of proteins called Yops (Yersinia outer proteins) Some enter macrophages, neutrophils and other phagocytes, and disrupt phagocytosis Others block the cell signaling between immune system proteins • Other proteins invoke a cytokine storm • Thus, instead of being destroyed, the Yersinia is taken to the lymph nodes There it is able to replicate almost without limit, creating buboes • If the patient is lucky, the infection will remain restricted to the lymph nodes; the buboes will burst, and the patient has some chance of survival • If, however, the infection works its way into the blood as well, it can become systemic • One route: bacilli circulate in blood, and become so numerous they clog the capillaries • Leads to necrosis around day 3-4 During a systemic infection, Yersinia can also make it to the lungs • Lung capillaries rupture, host coughs up blood, dies • Coughing can transmit Yersinia to another human - leading to the pneumonic version of plague Straight to the epithelial cells and capillaries of the lungs Leads to death within hours • Meanwhile, if the flea injects the Yersinia straight into a capillary, necrosis and death can occur in a matter of hours rather than days Plague thus leads to death quickly among most human infections. • For many pathogens, this would be an evolutionary dead end, especially in populations at pre-industrial levels • Two reasons this is OK for Yersinia pestis: The main pathway to death involves a symptom (buboes) that greatly enhances the contact with the vector It is a souvenir pathogen for humans; even if we are a dead-end for Yersinia, it can persist in rodents Given how deadly it is, plague cannot survive forever in humans alone • But under what conditions can it survive in rats, given how deadly it is?

Smallpox

Caused by variola virus of the genus Orthopox Variola major: more severe version Variola minor: less severe version • Other orthopox viruses cause similar diseases in other animals: Buffalopox, Camelpox, Cowpox, Monkeypox, Mousepox, Raccoonpox, Volepox Taterapox (gerbils) • Variola is most closely related to camelpox and taterapox • Double-stranded DNA virus with one of the slowest mutation rates known • One section of the genome (about ½ of the total length) is conserved among all the different species • Largest animal viruses Figuring out the date that variola emerged from the others is harder than for most other pathogens • Hinges on recent realization that West African and South American versions are most similar to each other • They would presumably have split from each other during the early slave era • This gives a date for the rise of variola from either camelpox or taterapox about 3000-4000 years ago This is more recent than the estimate that was current when Crawford wrote • Still encompasses all of the relatively well confirmed instances of smallpox: Later Egyptian papyruses Egyptian mummies Descriptions in Sanskrit texts • Origins are most likely somewhere in South Asia, but still unclear

The Global, Industrial World

Cholera Extreme diarrhea Long endemic to Bengal Cholera Caused by a bacterium (Vibrio cholerae) that is infected by a virus Without the virus V. cholera does not produce the toxin that invokes diarrhea A more common virus present in the area actually kills V. cholerae instead Monsoon rains upset balance among viruses Currently affects 3-5 million people per year, causes about 100,000 deaths, mostly children Treatment is with oral rehydration therapy Seven global pandemics, beginning with the British occupation of Bengal About 30-40 million deaths across all 2010-2 outbreak in Haiti - 7,000 dead 1885 Chicago cholera outbreak: 90,000 dead... Subsequent epidemics became smaller, even as the world population grew larger and more connected • Rise of modern medicine and public health

Plague of Athens

Commonly called the first epidemic documented in detail in the contemporary writings - in "History of the Peloponnesian War" by Thucydides • Whole region retreats behind city walls during siege • Food scarce - immune systems weak • Disease emerges - almost all of the common symptoms are mentioned somewhere in Thucydides: • Cough, sneezing, red rash, diarrhea, weakness, fever, stomach pain, headaches, spots, sleeplessness, gangrene, exhaustion, death • 1/3 to 2/3 of population dies, including most doctors and the military leader Pericles Plague of Athens 18 • Thucydides discusses: abandonment of social norms and mores religious fears • Sparta went on to win the war, although scholars disagree about plague's role • Brought end of "Golden Age of Athens" and of Greece more generally To this day, scholars debate whether it was typhoid, typhus, smallpox, bubonic plague or a viral hemorrhagic fever (like Ebola) • Genetic evidence remains inconclusive • May very well have been a whole variety

Themes

Connects the local and the global One of the best documented cases of the arrival of epidemics in indigenous small-scale societies ("virgin-soil") Reveals difficulties of reconstructing history, even with those records Reveals some commonalities in human response to epidemics

Development of Agriculture

a.k.a. the "Neolithic Revolution" • began 10-12 kya, unfolded slowly • Process sent by climate change, loss of large game • Initial benefit: dramatically increased human carrying capacity • Scholars have heavily debated other benefits and drawbacks, but one drawback is clear..... • Pathogens!

Combatting disease

Dealing with symptoms • Preventing transmissions • Eliminating the pathogen Certain aspects require less of an understanding of the underlying microbiology than others E.g.: • tea has been used for millennia in societies around the world to deal with symptoms from various infectious disease • current state-of-the-art treatment for cholera = "oral rehydration therapy"

HIV epidemic - early years

Doctors in New York and California have diagnosed among homosexual men 41 cases of a rare and often rapidly fatal form of cancer. Eight of the victims died less than 24 months after the diagnosis was made." "The sudden appearance of the cancer, called Kaposi's Sarcoma, has prompted a medical investigation that experts say could have as much scientific as public health importance because of what it may teach about determining the causes of more common types of cancer." "Cancer is not believed to be contagious, but conditions that might precipitate it, such as particular viruses or environmental factors, might account for an outbreak among a single group." "Dr. Friedman-Kien said he had tested nine of the victims and found severe defects in their immunological systems. The patients had serious malfunctions of two types of cells called T and B cell lymphocytes, which have important roles in fighting infections and cancer." By the end of 1981, there are 159 reported cases in the US 1982: Number of cases continues to grow among gay men Cases begin to be reported in hemophiliacs, persons of Haitian origin, and users of intravenous drugs Scattered cases in children as well Scattered cases begin to appear in other countries Term "AIDS" is coined By end of year, 771 known cases and 618 deaths Meanwhile, in Uganda, a new wasting disease ("slim") appears Growing awareness in the (relatively newly emerged) gay community: something very very bad is happening 1983: AIDS cases reported in over 30 countries, including a large cluster reported in Central Africa Virus identified by two research teams independently 1985: HIV test developed • 1986: Lyndon LaRouche (and may others) call for mandatory lifetime quarantine of everyone with AIDS • 1987: 1985: first AIDS drug (AZT) patented • 1987: first AIDS drug approved for use early 1990s: spread in Southeast Asia, East Africa become clear • cultural responses in US

Look at resistance alleles

E.g. malaria/sickle cell gene • 0 copies of the HbS allele - "wild-type" • 1 copy of the HbS allele (from either parent) - resistance to P. falciparum malaria (makes it difficult to enter cells) - heterozygote • 2 copies of the HbS allele (from each parent) - sickle cell anemia - homozygote Duffy blood group Two copies of the "Duffy negative" alleles = resistance to P. vivax Duffy negativity has no known negative consequences This version of malaria is less deadly than P. falciparum, but still causes disease and death

Origins

Earliest origins of Y. pestis slowly being revealed through genetics - return to at end • Plague of Justinian recently shown to be Bubonic Plague (1st Bubonic Plague Pandemic) • Black Death = 2nd Bubonic Plague Pandemic Spread made possible by the Mongol Empire

Large populations

Enabled directly transmitted diseases -e.g. Tuberculosis, leprosy / Hansen's disease

Large pops combined with sedentism

Enabled water-borne, soil-borne, fomites -E.g. worms, schistosomiasis

Large pops combined with contact with livestock

Enables unparalleled level of zoonoses -E.g. measles, mumps, smallpox, diphtheria, whooping cough...

Protozoa

Example: Plasmodium spp. (vivax, falciparum, etc.) Anopheles mosquitos can live up to a month or so And can travel over a mile or so

How to tell if it's older than agriculture?

Find an ancient skeleton, extract DNA, find either pathogen or show the person had a resistance allele Use phylogenetic dating methods on the pathogen Look at patterns in resistance alleles in the host Genetic recovery of the pathogen itself • Still very rare for pre-agricultural specimens • But possible in some very specific circumstances • E.g. Chagas disease ("American trypanosomiasis")

Re-appearance

First wave over by 1352 • Frequent, repeated local outbreaks throughout the continent for the next 400 years • E.g.: Major outbreaks in England in the 1360s, 1470s, 1600s, 1660s And dozens of others Any given outbreak might kill 50,000 to half a million people Final outbreak in Western Europe in Marseilles, France, in the 1720s • Plague persists in the Middle East (Ottoman Empire) much longer E.g. outbreaks in Baghdad in the 1680s, 1770s, 1830s, 1870s

1853 outbreak

Focused in modern-day Washington, especially Puget Sound • Estimates suggest less than 12,000 Native people throughout Puget Sound region, from 32,000 before • Third massive smallpox epidemic in a century, along with others • Smallpox vaccine was available in area by this time British (Canadians) help to vaccinate Natives near Olympia • Washington Territory is formed by the US government in..... • Most tribes of Puget Sound sign Treaties with US Government, instituting reservation system, in: American settlement explodes • 1861: UW founded Focused in modern-day Washington, especially Puget Sound • Estimates suggest less than 12,000 Native people throughout Puget Sound region, from 32,000 before

Imagine that malaria (P. falciparum and/or P. vivax) has just appeared for the first time ever in humans, and neither of the resistance alleles we've discussed exist • What steps need to happen before genetic resistance to malaria is widespread in the area? • For each of the two alleles: Will that process be quick or slow? Why? Where will the process end up?

Genetics 20 • However, natural selection can be *slow* in humans, especially when an allele appears that is only advantageous when someone has two copies • The field of population genetics allows one to turn information about: the frequency of a gene the population sizes and mating patterns the nature of the selection operating on it the strength of the selection operating on it and determine how long ago it likely arose

Germ theory - the breakthrough

Golden Age of Microbiology • 1860s: Pasteur conducts pioneering experiments on fermentation Disproves spontaneous generation • 1876: Koch identifies anthrax bacterium • 1870s: Lister develops methods for sterile surgery • 1884: Koch identifies Tb bacterium, develops postulates • 1880s: Pasteur develops anthrax and cholera vaccine • 1891: antibodies discovered • 1892: viruses discovered • Golden Age of Treatment • 1912: first treatment for a bacterial disease (syphilis) developed • 1929: first antibiotic developed (penicillin) • 1953: DNA structure identified • 1962: first antiviral developed (for herpes) • Etc. etc. etc. Cycle for any one pathogen: • Identification of pathogen • Identification of mechanisms of operation • Development of vaccines • Development of treatments Replaces miasma theory • Integrates with, rather than displaces: sanitation, nutrition, symptom management • E.g. malaria in the US, 1942 Main strategy remains swamp drainage

HIV

HIV incidence has recently been on the rise in: China Indonesia Philippines Pakistan Middle East Eastern Europe 18-25 year olds in developed countries, especially the US

Origins hiv

HIV-1: crossed from chimpanzees to human at least four separate times the first (and main) one likely in the early 20th century • HIV-2: crossed from sooty mangabeys to humans, probably mid-20th century

Leper Settlement" at Moloka'i

High rate of leprosy in Hawaii post-contact • Mid-19th century: Hawaii is an independent constitutional monarchy with growing American presence and influence • Leprosy becomes increasingly stigmatized • King Kamehameha signs the 1865 Law to Prevent the Spread of Leprosy Criminalizes having Hansen's Disease • Requires lifelong internment • Initially the colony had virtually no financial support, no medical care, no food systems • Belgian priest Father Damien and others step in to improve conditions • 8,000 Hawaiians sent there over a century Throughout the early 20th century - more details of Hansen's disease transmission came to be understood • Hansen's disease was rendered non-infectious with antibiotics in the 1940s • Law repealed in 1969 • Current residents allowed to stay for life if desired • Today, 14 residents remain Report enormous continued stigma • In transition to Kalaupapa National Historic Park

Smallpox epidemic of 1770s

How do we know that there were epidemics at this time? Reports by Native survivors themselves (usually recorded by European/American explorers) "According to Saigakakh there was an epidemic of smallpox there some 50 years ago, that is about 1770. He was a small child then and barely remembers it, but he knows for a fact that there were only one of two persons left in each family." Reports by explorers of smallpox scars on Native survivors by age "I observed the oldest of the men to be very much marked with the small-pox, as was a girl who appeared to be about 14 years old....I did not observe any of the children under 10 or 12 years of age that were marked." How do we know that there were epidemics at this time? Reports by explorers of abandoned villages "If we may judge from the numerous villages which bound this and many other parts of the inland navigation and which now are left to decay, it is to be supposed that it was once the principal retreat of the Northwest Americans." But must be careful with this! Reports by explorers of smaller population sizes than seen by previous visitors " I expected to have seen a numerous tribe, and was quite surprised when I found it consisted only of three men, three women, the same number of girls, two boys about 12 years old, and two infants

Forager pathogen burden

How do we know? • Overall clue: we have an immune system, including an adaptive immune system! • Additional sources of more specific evidence: Paleopathology Consideration of: • pathogen characteristics • human practices • environment, including other species Genetics

Socio-economic implications

Huge historical debate about the role of the Black Death in the many subsequent changes in Late Medieval Europe • Most attention focuses on the increased quality of life for peasants, and their eventual liberation from serfdom • Difficult (impossible?) to say for sure whether they would have happened anyway • Nevertheless, many scholars believe in a strong casual link • Think of Malthus Humans are easily capable of having >2 children per couple From that consideration alone, human populations should grow exponentially • E.g. if average family size is 3, then: But when the resources available to feed people are fixed, they can't grow exponentially Carrying capacity Problem! What happens as a result? 1. People limit fertility 2. People take over new territory 3. People innovate and figure out ways to increase the yield of the territory they have 4. Lots of people die miserable deaths (starvation, disease, war) Historians argue that the sudden surplus of land relative to people meant that, once the Plague had passed, living standards would increase for some time Moreover, the fact that the Plague affected the peasants more than the landowners mean that there was now a labor shortage • E.g. peasant wages in England rose 30% from the 1340s to the 1360s. • A series of major peasant revolts occurred throughout Western Europe in the latter half of the 14th century • Serfdom (peasants tied to a master's land and required to farm it) declined, and mobility increased • What role did the Black Death play???

PNW in the 1760s

Hunter-gatherers • Rich temperate marine resources allow for very high densities for HGs • Huge cultural and linguistic diversity • Structured primarily as small, interwoven cultural groups • With some distinctive, shared traits

Europe

In the Mediterranean, Genoa is emerging as a major seafaring power, along with rival Venice • Ozbeg, the Khan of the Golden Horde, allows Genoans to establish trading posts in Crimea - chief among which is Caffa Ozbeg's son Janibeg inherits the throne • Decides he wants all of Crimea back • Lays siege to Caffa in 1345 • After many months, his army experiences a severe outbreak of Bubonic Plague • Force is weakened, and must retreat • Genoese writer Gabriele de' Mussi later states in his memoir: "The dying Tartars, stunned and stupefied by the immensity of the disaster brought about by the disease, and realizing that they had no hope of escape, lost interest in the siege. But they ordered corpses to be placed in catapults and lobbed into the city in the hope that the intolerable stench would kill everyone inside. Whether or not the plague corpses actually happened has long been a matter of scholarly debate • One recent historical review concludes: Probably did happen But probably didn't matter

Middle East

Infects Byzantium/Constantinople/Istanbul -then still the capital of the Byzantine Empire • Spreads throughout the MamlukEmpire based in Egypt • Kills 1/3 - 1/2 of the population? • Destabilizes power structures • Helps rise of Ottoman Empire?

Mary Mallon, aka "Typhoid Mary"

Irish immigrant cook in NYC in early 1900's • Over 7 years, a string of wealthy families develop typhoid, with at least 3 deaths • Investigator uncovers a startling fact - they all had the same cook • Every time a family got sick, she left • Tracked down, does not cooperate with investigation • Adamantly insists she is unrelated because she has never had typhoid • Refuses to stop working as a cook • State quarantines her in 1907 After 3 years, the state allows her to leave if she promises never to work as a cook again • She agrees, is released, is given a job as a laundrywoman • She disappears • 1915: typhoid outbreak in a hospital - 25 infected, two dead • She is discovered working there as a cook under a pseudonym • Had been working all along as a cook, with numerous typhoid outbreaks • Re-quarantined for the rest of her life (33 years) • Upon her death, her gall bladder is discovered to have living typhoid bacteria Mechanism for asymptomatic carriers only identified in 2013: bacteria hides in macrophages

Western Hemisphere

Isolated from Eastern Hemisphere since before agriculture • Before 1492: 50-100 million people 100 years ago: most scholarly estimates were more like 10 million • Two major concentrations Certainly sufficient concentrations to sustain endemic diseases, although: Concentrations were smaller and fewer overall Later development of agriculture also perhaps meant less time for human pathogens to develop Number of species of domesticated animals far smaller Level of interactions with them far smaller North-south orientation of continents meant smaller areas of consistent climate • For these and perhaps other reasons: The imbalance in endemic pathogen load was enormous

Characteristics making a pathogen more likely to persist in hunter-gatherers: 2

It is able to create a long-term infection in humans E.g. chicken pox - the only one of the "childhood diseases" that does so • Has mannose 6 phosphate on its envelope, which attaches to receptors on nerve cells • Hides out there for many decades • Eventually re-activates, causes rash on the skin nearest the nerves ("shingles") • Can transmit to others as new chickenpox case West African trypanosomiasis (T. brucei gambiense) slow onset chronic trypanosomiasis in humans

Characteristics making a pathogen more likely to persist in hunter-gatherers 1

It is transmitted via a vector that is dense and can travel • e.g. Malaria - caused by four different protozoa of the genus Plasmodium • Still among the top 5 causes of death in the developing world • P. falciparum is the most lethal; other three are more mild • All are carried by mosquitos of the genus Anopheles

Characteristics making a pathogen more likely to persist in hunter-gatherers:

It is transmitted via a vector that is dense and can travel •Trypanosomiasis (African sleeping sickness) •Two versions (both subspecies of Trypanosoma brucei) •Both carried by tsetse flies •Like malaria, is bloodborne and causes extreme lethargy

Leprosy

Leprosy 15 • Originated South Asia or East Africa, spread around world from there • Would indeed have been in Middle East in time for religious texts • Introduced into W Hemisphere ~500 ya • Can trace specific connections, e.g. "For instance, in the 18th and 19th centuries, when the midwestern states of the United States were settled by Scandinavian immigrants, many cases of leprosy were reported and, at that time, a major epidemic was under way in Norway (26). • Science, 2005 • Phylogenetics of M. leprae from many people

Schistosomiasis

Macroparisitic(worm) infection (Schistosoma spp.) • Early symptoms: lethargy, fever, aches • Years later: organ damage, blood in urine • S. haematobium unique in using bladder instead of intestine • Disease of agriculture because: • Snails live primarily in stagnant water, i.e. irrigation canals Clearly tied to the rise of irrigation in the Nile Valley in Ancient Egypt • Mummy of Nakht (1200 BCE) - autopsied in the 1970's preserved tapeworm ova of the Schistosoma haematobium changes in the liver resulting from a schistosomal infection Since 1937, some scholars of Egyptian believe that the word refers to hematuria (blood in urine), given: • Its hieroglyph is indeed a discharging penis • It appears in one quote (mentioned by Crawford), about a treatment to give to men "in whose belly are worms; the aaa produces them" But some references talk about "aaa of the heart", or driving out "aaa from a goddess" Crawford follows the most common hypothesis and translates it as "haematuria" but scholars are still divided

Remember critical population size

Measles is very big (300k-500k) Others smaller, but larger than HG populations As human settlements increased, more and more pathogens could take hold So, how big were human settlement sizes through time?

Smallpox biology

Only infects humans • Like many other full-body rash pathogens: Respiratory Hitches a ride to the lymph nodes After a few days, enters the blood stream Spreads to many organs • Has two main immune system escape proteins SPICE (Smallpox Inhibitor of Complement Enzymes) CKBP (Chemokine-Binding Protein) Around 8th - 14th day, begins to kill a significant number of cells • Prodromal symptoms appear (fever, headache, lethargy, etc.) • Virus is present in large numbers in spleen, kidneys, liver, bone marrow Then the rash (pox) appears, beginning in the mouth • Highly contagious • Pox then spread throughout body • These become blisters on the 3rd day, infected pustules by the 7th • Death common at this stage (~30%) Pneumonia Internal hemorrhage • If survival occurs, pox dry up and scab off • Variola minor genetic offshoot that progresses more slowly and only kills ~1% of the time identified in South Africa and the US around 1900 Reached perhaps 10% of all deaths in some areas in some times • Direct respiratory transmission = disease of the rich as well as the poor Introduction into Western Hemisphere in Columbian era • Only one part of the broader spread with European colonialism

Preventing transmissions

Methods can have a range of effectiveness even with incomplete understanding of ultimate cause Perhaps the oldest method: quarantine • Religious texts • Suggest some understanding of a contagious element • Developed even where theories of disease were multi-faceted • E.g. Bubonic Plague: Caused by a bacterium carried from person to person by fleas on rats 14th century outbreaks in Europe • No concept it was related to bacteria, fleas or rats • But - it always seemed to start in a port city and then move inwards • Hmmmmm.....

Sanitation

One perpetual school of thought held that infections were environmental - caused by "bad air" or "bad humors" or "smells" or "miasma" • Roots in China, India, Greece, elsewhere? • Took on new life in 18th c. Europe and onward Led to wide-scale movements for: Increasing ventilation Draining swamps Converting stagnant water to flowing Initiating garbage collection Removing refuse with water Prohibitions against spitting Establishing Sanitation Boards and Health Departments to handle all this Growing sense of the importance of personal hygiene and diet • E.g. Father Damien of Molokai acquired Hansen's disease in 1884 • His Japanese doctor prescribed him "nourishing food, moderate exercise, special ointments, and medical baths"

Variolation

Predates knowledge of pathogens and the immune system by at least 400 years! • Give healthy person small amount of material from a person suffering from smallpox (variola) • Chinese version - Grind a smallpox scab into a powder, blow it up the patient's nose • Indian / Middle Eastern version Collect pustules from people who were just inoculated Store them for a year Prick skin on patient's arm, introduce inoculate • Both led to mild symptoms with subsequent immunity....in most cases. typically 1-2% of children would die compared to perhaps 25-30% of those who acquired it naturally

vaccination

Spread began quickly, but then took generations to become fully accepted 1796 - Jenner's first vaccination 1840 - Britain outlaws variolation 1853 - Britain mandates vaccination

Attempts at control

Quarantine Of ships Of individuals and families • In hospitals • In homes, by force • Via exile, by force Of whole communities • From without, typically by force • Sometimes from within by choice (Eyam) Of whole regions Local prevention and care Eliminating bad air / miasma / smell Blocking smell with masks and herbs Regulating burials Burning of victims' clothes, bedding, home

How do we identify ancient pathogens?

Same methods as before: 1. considering pathogen characteristics + human lifestyles 2. paleopathology 3. genetics Plus two new ones: 4. Written records 5. Art and visual records

Use phylogenetic dating methods on the pathogen

So, P. falciparum arose ~ 5-7 million years ago • And it mostly infects humans • Possibilities Has been infecting humans for 5-7 million years Was infecting chimps or other apes for most of that time and only switched to humans recently Genetic diversity within P. falciparum Crawford reports on inconsistent and inconclusive studies Subsequent work: P. falciparum genetic diversity is old (100,000 - 300,000 yo)

African-origin diseases in the Americas

Spanish began the practice of importing slaves from Africa to the Americas, c. 1501 • Taken up by other European colonial powers as well • In total, scholars estimate 12-20 million people were brought from their homes in Africa to the Americas as slaves African-origin diseases in the Americas 20 • Led to the transfer of additional diseases, especially tropic-to-tropic • Malaria: took some time because the Anopheles mosquito vectors can only survive a month at most

student q black plague

Student questions 4 • Was the black plague really the most deadly epidemic, or just the most well known because it was in Europe? Second plague epidemic Columbian epidemics 1918 flu Total deaths 30 million in first wave? 50-100 million total? 50-75 million total? 50-100 million? % world pop 7% in first wave? 10-20% total? 15-20% ? 3-6% ? Time course 5 years for initial outbreak, then continued local outbreaks for 350+ years 200+ years 2 years Affected populations Europe Middle East China? Native peoples of Western Hemisphere worldwide

West to East: Syphilis

Syphilis Sexually transmitted infection from the bacterium Treponema pallidum Also can be passed from mother to child Has three stages • Primary syphilis: genital sore within a few weeks of infection • Secondary syphilis: rash throughout body for 2-3 months after • Tertiary syphilis: after years of asymptomatic infection, can re-emerge in the form of: - Gummas - Neurological damage - Heart damage First appeared in Europe in 1493/4 • Primary syphilis made the connection to sex clear early "Don Christopher Columbus, who had relations and congress with the inhabitants of the island during his stay" • Columbian theory vs. pre-Columbian theory • Various researchers have claimed evidence for syphilis in pre-Columbian skeletons in the Eastern Hemisphere

Eastern Hemisphere

That population sees an epidemic, lots of deaths, but then it recovers. • The disease stays around and continues to be a killer, but ceases to be devastating at the social / political / economic level Not killing as many people Not killing all at once Mostly killing kids • Other factors might also cause it to decline even further: Humans change behavior Humans develop partially effective treatment Humans evolve resistance to it Pathogen evolves to be less virulent Repeat, repeat, repeat.... • Note - not all spread. Would be blocked if: Vector / secondary host not present in new location Climate not suitable in new location Cultural practices differ in new location • Note: long-distance travel at this time was overland, and therefore slow

HIV-1 biology

The 1 in HIV-1 • 35 years • 60 million infections total • 25 million deaths total • 35 million currently infected • Everything about the dynamics of HIV is different than the examples we've discussed so far because: Sexually transmitted Causes long-term infection with infectiousness throughout RNA retrovirus - two separate single strands • reverse transcriptase • gp surface proteins - latch onto receptors on the surface of immune system cells Reverse transcriptase to copy its RNA into DNA • Inserts this into the hosts own DNA using the enzyme integrase • Host cell replicates and translates HIV along with own DNA Primarily infects cells with CD4 receptors: Macrophages Dendrites Helper T-cells • Begins with dendritic cells and macrophages (using the CCR5 co-receptor) near the mucosal linings • Hitches ride to lymph nodes • Spreads over time to T-cells (using the co-CXCR4 receptor) • Is able to infect cells latently - that is, reside in the DNA of the cell, undetectable by all immune system cells • Only when they replicate will they be detected • But also needs to infect some active cells Like all retroviruses, HIV's mutation rate is extremely high • Within each host, it re-evolves the ability to infect different types of cells • Killer T-cells end up killing the helper T-cells that the virus is invading • T-cell count declines, body cannot fight off other pathogens • Opportunistic infections ensue

Historical records and specific epidemics

The big three: Plague of Athens (430 BCE) Antonine Plague (165-180 CE) Plague of Justinian

y. pestis

The discovery of Y. pestis occurred in 1894, during the Hong Kong Plague outbreak. • Race between two research teams: Alexandre Yersin, and Kitasato Shibasaburō • Kitasato initially published results that were likely contaminated • Yersin produced results with true pathogen, as did Kitasato a couple of days later • Often described as co-discovers Earliest origins of Y. pestis slowly being revealed through genetics - return to at end • Plague of Justinian recently shown to be Bubonic Plague (1st Bubonic Plague Pandemic) • Black Death = 2nd Bubonic Plague Pandemic Spread made possible by the Mongol Empire At its height, it ushered in the "Pax Mongolica" united most of the Silk Road under a single power Re-established it as a major route of trans-continental commerce Ushered in the "World Trade System"

Tuberculosis

Tuberculosis 10 • a.k.a TB, consumption • respiratory disease caused by Mycobacterium tuberculosis • Obligate human pathogen • Only 10% spreads into other organs, causing major symptoms (bloody cough, fever, weight loss) • Remains one of largest killers today • Heavily dependent on urbanization Tuberculosis 11 • Leads to a specific set of markers in lungs • Some cases penetrate the spine or other bones (osseous tuberculosis)

Race, power and infectious disease research

Tuskegee Study of Untreated Syphilis in the Negro Male Begun in 1932, by the US Public Health Service Aimed to determine the range of outcomes in untreated syphilis No treatment existed when study began Enrolled 399 poor Black males in rural Alabama who had syphilis None told they had the disease, nor the purpose of the study Given small financial incentives and basic medical care In 1949, penicillin becomes standard of treatment nationwide for syphilis Men still not told they have syphilis, nor given treatment Men deterred from obtaining treatment elsewhere Study continues until 1972 Ended by a whistleblower who leaked it to the NY Times and Washington Star By end, > 100 men had died of syphilis or its complications 40 wives infected 19 children born with congenital syphilis

Vaccine debates

Vaccines protect individual from infection • Not everyone can be vaccinated (e.g. newborns, those with allergies or weakened immune systems) • Herd immunity can lead to indirect protection for them as well • Mandatory vaccination rules began in the US with Massachusetts (1855) Upheld by Supreme Court in 1905 • Only reached all 50 states in 1980 • In the US, these rules have long had religious exemptions (48 states) • Over the last few decades, these have expanded to include "philosophical exemptions" in 15 states, including Washington • However, that trend is reversing • The battle over this issue is fierce "Vaccines are safe and effective. However, they are neither perfectly safe nor perfectly effective." - CDC The situation is generally straightforward when the risk from the vaccine is less than the risk from the disease, and the disease is very common But what about after that? What about when both are very very small? And what about when the risk from the disease then depends on other peoples' decisions? Overstatement of risk Widespread MMR-autism controversy • Fueled by Wakefield et al. (1998) -Subsequently found guilty of willful fraud -Subsequent re-analyses found no evidence -Meta-analyses of studies that collectively involve millions of children find no evidence • Fueled by the fact that autism diagnosis has been on the rise in recent decades • Fueled by the fact that autism generally shows first symptoms right around age 1 -4 million children born in each year in US -About 50,000 will be diagnosed with an autism-spectrum disorder -Just by chance - 900 kids a year or so would show their first sign of autism within a week of their MMR shot But risk is not 0 • In theory, varies by vaccine type Non-infectious / inactivated / dead • Killed, but surface protein(s) intact • Flu shot, typhoid, cholera, pertussis • Only activates B cells • Lower success rate, usually requires boosters Live attenuated - living but weakened • Pass through a foreign host (animal, egg, tissue) • Flu nasal spray, tuberculosis, measles, mumps, rubella, yellow fever • Activates additional parts of the immune system • In theory, can revert through mutation • In practice, only happened with the oral polio virus - now replaced Carrier (aka conjugate) • Use genetic engineering to combine antigen with carrier protein • Meningococcal, pneumococcal

Foraging

Very small (usually <50) nomadic populations • Of enduring interest in anthropology and popular culture • Overall relatively little infectious disease burden relative to agriculturalists But still not insignificant (and hotly debated)

The End of the Second Plague Pandemic

Why did it finally fade out? Many theories: Improvements in housing and sanitation reduced the rat and flea populations Improvements in nutrition improved immune response Quarantine methods became more effective The dominant rat species changed - the brown rat slowly replaced the black rat Y. pestis evolved to be less virulent or humans evolved to be more resistant?

Yellow Fever

Yellow Fever Caused by an RNA- based flavivirus Infects various African primates without symptoms Transmitted by mosquito Aedes aegypti "souvenir pathogen" in humans First human virus identified (Reed) Aedes aegypti survived and spread throughout the Americas • Survived not just in tropical swamps, but in in stagnant water in urban settlements through the two continents 1793: United States is a fledgling 10-year old nation • Philadelphia is its capital and largest urban center, at 50,000 in the city and its suburbs • In the Philly epidemic: 5,000 died over three months (Aug - Oct) 20,000 more fled the city (including George Washington) Baltimore and New York set up barricades • Dr. Benjamin Rush identifies the epidemic based on previous experiences with malaria - assumes that many Blacks would be immune urges the city's small Free Black population to act as caregivers "Early in September, a solicitation appeared in the public papers, to the people of colour to come forward and assist the distressed, perishing, and neglected sick; with a kind of assurance, that people of our colour were not liable to take the infection. "Upon which we and a few others met and consulted how to act on so truly alarming and melancholy occasion. After some conversation, we found a freedom to go forth, confiding in Him who can preserve in the midst of a burning fiery furnace, sensible that it was our duty to do all the good we could to our suffering fellow mortals. We set out to see where we could be useful. The first we visited was a man in Emsley's Alley, who was dying, and his wife lay dead at the time in the house, there were none to assist but two poor helpless children. We administered what relief we could, and applied to the overseers of the poor to have the woman buried. We visited upwards of twenty families that day—they were scenes of woe indeed! The Lord was plentiful to strengthen us, and removed all fear from us..." Ironies: Care wasn't actually effective • Mostly bloodletting and purging Caring for the sick wasn't actually that much more dangerous than just being in the city Blacks had no resistance, and died at the same rate as Whites

TB sanitorium movement

places where tb victims were sequestered; urban

the eastern hemisphere...

was all linked together by trade