Bio Exam 1

Risks of Antibiotic Therapy

"Missing Microbes" -When you take antibiotics, you kill bad AND good bacteria *Humans and bacteria co-evolved *Positive values for all of "normal" germs -Even "pathogens!" -Helicobacter pylori and GERD (ulcers) - when you eliminate it you get acid reflux symptoms - because you need it (controlled amounts) *Elimination -Antibiotic use to cure (needed or not) (no money for pharmaceutical companies. So they invent acid reflux) - C-section - Antibiotic use in cattle and fowl In natural birth, after water breaks the lower range is flooded with lactic acid bacteria - that's the first thing the baby is colonized with. With c-section, babies first colonized with skin bacteria (Staff). Correlations between C-section, autism and allergies

Mary Mallon: Class Issues

* Progressive era -caring but condescending? -is it different now? *Heirarchic expectations (both sides) -she was expected to obey -she expected to be cheated *Working class -Job options - no "safety net" - Class solidarity during her escape from Josephine Baker (tracking down Mary)! -differences between Mary Mallon and Josephine Baker *Did it matter? -What if member of a "prominent family?" -What if propertied?

Key to health is balance

*Bad germs always with us, often IN us *Kept under control and sometimes even useful - pneumonia -Staphylococcus (Staph)

Epidemiology of Cholera

*Begins in 1817 "Asiatic Cholera" *"Seven" pandemics since then -First six are "classical V. cholerae O1" -Current one is "V. cholerae El Tor" *We'll look at three epidemics in Europe *Definition of "epidemic" and "pandemic" Travel - ships to trade in asia spread it Outbreak - wasn't there before and now it's there- then it goes away Endemic - something that is always there at some level (colds, flu in the US) Epidemic - outbreak that covers a large region Pandemic - across a much bigger region (multiple continents)

Cholera Infection

*Causative agent Vibrio cholerae *Grows in humans, but also in environment -salt water best -"viable but non-culturable" -association with chitin (shellfish) *fecal-oral transmission *contaminated water supply most common source --- Incubation *Normally requires high dose (about 100 million to a billion cells) for infection *Antacids reduce that by ten-thousand-fold! (so you can get chlorea a lot easier - it tells you that stomach acid is a huge protector) *(Data from infecting prisoners)

Evolutionary Time

*Earth cooled ca. 4.5 billion years ago *Bacterial fossils ca. 4 billion year ago -photosynthetic already *Eukaryotic fossils ca. 2.5 billion years ago *Bacteria - by far the first living things *Bacteria as highly evolved as we are (in some ways more - humans are stil tinkering with the nuances where as bacteria has worked it all out)

Comparing bacteria and humans

*Evolutionary separation means that lots of things are different *Similarity of all living things means that most things are the same SOME DIFFERENCES -How cells turn food into protein -How cells make DNA -The cell wall of bacteria (we don't have cell walls) -Vitamins - Special abilities of bacteria (they can do lots of things we cannot)

Prejudice and the Media

*Good or bad? -protective but restrictive, educational but conservative, simplifies but depersonalizes Effects on Mary Mallon *The Stereotype -This is a good example of how a carrier should not act. -See what can happen if you don't listen! * Media as friend or foe -The Newspaper Accounts: Early accounts were positive (in text), Early accounts had diabolical pictures, The need to sell papers, Tabloid journalism -March, 1907: Hearst's American broke the story first announcement of the concept of carrier (March 1907) -April, 1907 : There is one here in New York! (Mary Ilverson) Screaming headlines, "Human typhoid germ", "Presence kept secret". Pulitzer's World repeated it, then it died for 2 years - June 20, 1909: Court case.Probably financed by Hearst Banner pictures were demonic, cracking skulls into frypan, procession of those she infected, Text was quite sympathetic -June 30, 1909: She lost.Why should I be banished like a leper (3-column headline), Sympathetic drawings, Symphathetic text, Marriage proposal from Michigan! -After the 1915 Outbreak, negative, Use of pseudonym (Mrs. Brown), Maternity hospital, By 1930's all had softened

Alice Marble (1913-1990)

*Great athlete as a young girl by age 15 warming up with a minor league baseball team! Brother bought her a tennis racket in 1928 (age 15) to get her out of baseball? 1929: won her first tourney 1931 in the Nationals, 1932 ranked 7th! 1933 Whitman Cup team for US 1934 Collapsed with TB. Career Ended! Returned to US in wheelchair -improved in California sanatorium -doctors strictly forbade all physical activity. Letter from Carol Lombard (actress) said "FIGHT" 8 mo. later, she escaped from sanatorium 1 yr. after that, won the first of 3 consecutive championships died in 1990 at age 77 without any relapse

Effects of microbiota loss - antibiotics

*In cattle: more growth and fat -What about in humans? -Early development? -Even months after a treatment! Rise of "modern plagues" -Obesity (surprising?) - Allergies -Autism? What does antibiotics do for cattle - makes them bigger and fattier Increased # of treatments for people (by college age, 20 + courses) - obesity?

TB in Africa

*Nile region, common by 3000BC -skeletons, mummies, figurines and drawings *Sub-Saharan: Probably unknown until the Europeans brought it -some parts, not until 1850 or even 1900! *Now very common -- a true plague

Turn of the century (Typhoid Mary)

*Progress: Railroads, Steel and other Trusts *Rise of USA as world power: Spanish-American War, Teddy Roosevelt *Progressive Science: NYC Board granted broad powers, Modern lab facility, Hermann Biggs (24 years with city, more with state), Record of success * Other Typhoid sources disappearing: Water and milk kept clean, Sick are avoided, = increasing percentage caused by "healthy" carriers * Limits to Public Health Authority: -Fears of physicians (prevent but don't cure!), more later (Syphilis), untrained in microscopy and bacteriology - Cost: upper class resisted taxation, more later (Cholera in Hamburg)

Boards of Health

*Since colonial days, but usually transient -e.g. Yellow Fever in Philadelphia (1793) - P.S. Yellow Fever may have saved the US from its own destruction! - "Bring out your dead!" *Hospitals not always part of it *Enforcement of quarantine and sanitation

Effects of water flowing into intestine - w/ Cholera

*Small intestine recycles about 9 quarts per day *Large intestine recycles about another quart *Cholera overwhelms that -Water loss is in small intestine! *Death from dehydration is rapid (shock and general collapse)

Mary Mallon: Ethnicity: The Irish in America

*The American view of the Irish immigrants: Religion Poverty Drink and Temper Education Rising status (eastern europeans were newer) * The Irish themselves: History - Penal laws relaxed between 1830 and 1870 - taxation and tithes to Church of Ireland - ownership of property - religious restriction - language eradication - Independence delayed by World War I * The "English Question" - Americans were viewed as: - Allies of Irish hated England (revolution and civil war) land of opportunity - Allies of English protestant anti-Irish prejudice * Did it matter? Credibility Alien-ness

Bacteria in Real Time

*They grow fast ( some can double in number every 20 minutes) *Local increase can be explosive -What is "exponential growth" -The King's dilemma *Net growth (birth plus death) is zero - Double a penny a day for a month: - About 40 million dollars - Chessboard problem: -About 18,000,000,000,000,000,000 grains of wheat. (about the same as Mount Everest) - So even if a doubling takes -A year, a century, a million years..... (first bacteria 4 billion years ago - 4,000 doublings)

Legal Process, Typhoid Mary

*Vaccination case (1905): could require vaccination, penalties if not vaccinated, could not vaccinate, cf. could remove gall bladder *Mary's "Day in Court": 1909 -- two years later. Role of Hearst and his Newspaper. Argued on due process. Also her own tests and her own view *Question of Due Process: Health dept. as both police and jury Hermann Biggs: "Extraordinary and even absolute powers," No hearing or appeal, Commensurate (corresponding to size and degree) penalty, Uniform application

Miasmatic Theory of Cholera

*Von Pettenkofer's "experiment -Drank a vial of pure V. cholerae (no ill effects) -(Student [Rudolph Emmerich] did same, got cholera!) *Three factors required: 1) Specific infectious element (new idea!) 2) Porous soil with decaying matter in it 3) Toxic substance produced by these two

Current burden of Cholera

*WHO estimates - 3-5 million cases a year - 100,000-120,000 deaths a year *Recent outbreak in Haiti - After earthquake or 2009 - Traced to Nepalese UN peacekeepers (2010) -Political bickering ever since -About 700,000 cases and 9,000 deaths since 2010

Isolation as protection (or vengeance)? Typhoid Mary

*Why isolate the sick or carriers - Can't infect ME *Why isolate robbers and murderers? *Role of fear - Again, spies, homosexuals, communists, carriers, etc. - Whom do you fear? *"The selling of fear in America"

Chlorea and Dehydration

*massive diarrhea -- can be more than 1/5 your entire body weight in a single day! *symptoms of dehydration: -sunken eyes and cheeks -slow "pinch response" -rapid and weak or missing pulse *can be diagnosed on sight! *Death caused by dehydration: can occur in 12 hours or less - can be treated by rehydration

Cholera Pathology

*onset of symptoms usually 12-72 hours after ingestion -depends on dose *Vibrio cholerae don't invade cells, just attaches to small intestine *Secrete a toxin --- Cholera toxin has two parts: 1) an enzyme that damages the salt/water balance 2) a hormone-like part that fools the cell into taking it up -Every cell balances how much water goes in and out - cholera disrupts that Chlorea makes a protein that looks like a hormone so it attaches to the cell and the cell takes it in --- Cholera toxin inactivates the regulatory part of an important signal protein (adenylate cyclase) *causes Chloride to be excreted into small intestine (crypt cells) *blocks uptake of sodium chloride (and water) from small intestine (villus cells) *water follows salt - to balance it out (osmosis) -Cholera makes all your cells pump out salt - drawing all water out of body

Cholera cot

*plastic cot with a hole *calibrated bucket (measure output) *replace with "gatorade-like" ORS -orally if strong enough -nasogastric tube if not

Antibiotic therapy for Cholera

*reduces recovery time by half -2-3 days of diarrhea rather than 4-6 days *untreated, a few will become "carriers" for a few months

Disease

*sepsis (bacteria grow in blood and tissues) *intoxication (bacteria excrete poisons) *irritation (battle between invasion and defenses) -fever, swelling, redness, pain *overreaction (autoimmunity etc..) When Invasion Succeeds: Emergency! *Time is of the essence (they can always outgrow us!) *Multiple defenses used at once *All out war is declared

S. enterica

- Causes gastroenteritis ( body keeps flushing it every way it can - vomiting, diarrhea) - but it's always there -Usually food borne -eggs and poultry-how does it get there? -Usually untreated

The germ theory of disease

- The germ theory is new : Koch and Pasteur in the 1880's and 1890's, Rug dyes and agar - Germs and filth: Same or different?- Major policy issue -Germs as a target - Depersonalization of disease: Disease considered a normal part of human beings - "you are typhoid fever because you have typhoid fever" people = disease. With germ theory it became germs = disease

Recent trends in US - TB

-1953 to 1984, TB declines about 5% per year -1984 to 1992, TB increases about 3% per year (about 20% RISE!) -Declines again after recognition of public health importance -About 10,000 cases in 2012, down from about 30,000 in 1992 Since 1992: Increasing percentage in ethnic minorities Decline in US born, Steady in foreign born Result is that more cases in foreign born than US born. 27% of all cases were foreign born in 1992; 60% in 2012

WHO Cholera factsheet

-3-5 million cases (100,000 to 120,000 deaths) per year -Can kill within hours of symptoms -75% of infected show no symptoms (but excrete infectious V. cholerae for 1-2 weeks) -Other 25% (80% mild or moderate symptoms; 20% life-threatening symptoms)

Multiple-drug Resistant TB (MDR and XMDR)

-9 outbreaks in 1990-92 -mortality high (70%) and fast (4-16 weeks after diagnosis) -Treatment by historical methods and isolation -Between 1 and 5 cases found per year between 1992 and 2012

Some curious numbers about organisms

-Almost all organisms in the tree are microbes -The mass of microbial cells is about 25 greater than the mass of all animals combined (including elephants!) -There are about 1031 viruses and 1029 bacteria in the ocean (About 40% of bacteria are killed by viruses or eaten every day) -Bacteria outnumber human cells in us by 10 to 100 fold (What does it mean to be human, Germ free animals are alive but very sick, Most "germs" are good for us) -Bacterial genes in us outnumber human genes by about 150 fold -A teaspoon of soil has about a billion bacteria in it, made up of about a million different species

Fever

-Complex set of reactions - Temperature over 103°F slows many pathogens, kills others (especially over 105 or 106) -Gives more time for other defenses to work - Brings lots more blood to area (and more antibodies and phagocytes) -Fever is usually "good" : Not always good to reduce it unless it risks killing YOU (I.e. fever over 106 or more).

Typhoid Fever (21st Century Perspective) -Treatment

-If untreated (no treatment in 1906), by fourth week, symptoms subside, convalescence (recovery) begins, immunity develops - Fatal in about 10% of cases - Some become "healthy carriers" (about 5%) -Easily treated with antibiotics or prevented by vaccination (some strains resistant to some antibiotics) -Fewer than 500 cases a year in the US-Mostly travelers.

History of TB

-In general, Southern Europe thought it was contagious, Northern Europe thought it was not contagious -Renaissance led to learning, medicine, and cities -- AND an era of extraordinarily high incidence of TB -1800-1859 TB (Consumption) accounted for 20-25% of all deaths -Not certain it was a single disease and cause was unknown until 1880's -- Old in Egypt then on to Western Europe with cities Old in South America (North too) but not epidemic until reintroduction in 1700's Southern Africa, Pacific Islands, Russia, recent infection

Tuberculin Reaction

-Inoculate a naive guinea pig with M. tuberculosis, lesion heals quickly but the animal dies later -Inoculate a previously exposed animal, the lesion ulcerates, but does not spread -Does not require whole cells (culture fluid works) = tuberculin

Chlorea/Dehydration Therapy

-Intravenous solutions to rehydrate after dehydration sets in -Oral Rehydration to maintain fluid (and electrolyte) balance -Natural immunity follows and is both effective and long-lasting (lifelong?) -(Vaccines: 85% effective but only a few years.) Vaccines useful if outbreak - but just vaccines in general wouldn't work effectively cause you'd have to vaccinate everyone every few years __ Rehydration to replace -water (as much as 3-5 gallons a day!) -salts (mostly sodium chloride [salt] and potassium bicarbonate) -glucose (energy for transport and survival) -rice water stool isotonic with plasma, so replace quart for quart -Almost no one dies if you can get rehydration treatment

Missed opportunities (1990's view) - Typhoid Mary

-Never challenged "carrier = sick" -Never asked other public health experts - Never asked how many others there were: Carriers total, Cooks who were carriers -Judge ordered her confined as a threat

Good germs

-Nitrogen fixation -Oxygen production (plants too) -decompose organic material for recycling, otherwise it all ends up in the ocean -Normal flora are protective -Cleansing, digestive, protective -Recycling

Where are the human germs?

-On the skin -On (in) the GI tract -Rarely "inside" the cavities What places are "unfriendly" for germs and why: Second line of Defense Blood -iron limitation Urine - filtration Tears - lysozyme (digestive enzyme) Stomach -acid and enzymes (but Helicobacter pylori)

TB in the Americas

-Present in Paleolithic times but no epidemics until Europeans -pre-Columbian population ca. 60,000,000 -mostly in South America -only a few large population centers -Some North American skeletons show deformities that look like TB -A South American mummy from 700 BC shows acid-fast bacilli -deformed skeletons go back to 160 BC -most likely endemic in South America -agriculture in Peru goes back to ca. 6,000 BC -TB was rare in North American natives (reports from a priest in early explorations)

Healthy Carriers of Typhoid Fever

-Role of white blood cells (phagocytes)-engulf bacteria and form a small vesicle-fuse with a lysosome and kill the bacteria -Salmonella typhi blocks the fusion so they survive -Protection from the immune system (antibodies) -Can lodge in gall bladder and elsewhere * Could all carriers be found? -Typhoid was "reportable" but problems with physicians: stigma, loss of work and patients, opposition to state medicine

Human Defenses from germs & Bacterial counterattacks

-Skin (physical barrier) -Acid (chemical barrier) -Iron (starvation barrier) -flushing (wash them away) -competition for space (good germs fill all the places) Human body's weapons to repel the invasion: *White blood cells (phagocytes) phago=eat, cyte=cell *immune response *fever Bacterial counterattacks: -iron limitation: scavenging chemicals -filtration: swimming upstream -enzymes: slime coats -acid: neutralizers

Human Anthrax (historical)

-Skin anthrax from handling infected animals and wool -"Woolsorters disease" from breathing dust form wool -Both were bad

Typhoid Fever (21st Century Perspective) - Cause

-Spread fecal oral contamination, contaminated water (sewage), contaminated milk or produce (had on hands and milked cows), dirty hands -Water treatment plants eliminated most sources of contamination

The issues in the case of Typhoid Mary

-The priesthood of medicine (why can a doctor say "you are infected, you'll go to jail for the rest of your life" - priests controlled life/death all decisions - doctors really do this now; rise of the clinical worldview -Public policy: truth and necessity (what is true is not always necessary to utilize in daily life - like the earth is round), the possible and the politically acceptable - Legal issues: public safety vs. individual rights, arbitrary vs. scientific -Social issues: class, gender, ethnicity -Mass media: shaping a world view -Mary Mallon the person: She had a real name! -The modern perspective

Estimating infection rate

-Tuberculin skin test (more later) (if not "vaccinated" with BCG) -Sputum smears for "acid fast" bacteria -waxy walls of Mycobacterium -1% annual risk (tuberculin test) = ca. 50 smear-positive cases per 100,000

Role of Immune System - & TB

-Until AIDS, nobody understood latency and reactivation -Now we know it is balance between immune systems and M. tuberculosis -Explains why sanitoria worked Good food, rest, exercise, -- generally good health led to stronger immune system

Problems with treatment of TB

-can live inside white blood cells -can hide without causing symptoms -Waxy coat on bacteria (Mycobacterium)

Anthrax

Bacillus anthracis: Cause of anthrax Found in soil Pathogenic for grazing animals Humans get if from animals (or from intentional inoculation- terrorists) B. anthracis makes spores that are very hardy survivors

History of the Black death

-endemic in Mongolian marmots (tarbagans) -Opening of "Silk Trail" led to explosive expansion -1338-39 Issyl Kul (Lake Balkash) Nestorian cemetery -Reached Kaffa (Theodosia) Crimea by 1346 Was it all Yersinia pestis? epidemiology and speed make it likely some question of TB or even Anthrax too lack of mention of rat die-off lack of mention of buboes in some accounts But this is absence of evidence, not evidence of absence Use of Hagiography (Lives of the Saints) Why 1347? New species of rat in Europe (not there in 700s) High population density Better ships allowed year-round trade lasted until about 1700 Why did it go away? Great Fire of London -thatched roofs (rat and flea infested) replaced with tile - "The fire drove away the pestilence" -More stone building (wood shortage as population increase began anew) -New species of rat -- more "people shy"

Cause of TB

-growth in lung tissue -surrounded by white blood cells, walling off the damaged area = tubercle -eventual calcification of the lesion (easy to see on X-rays) -if not walled off, liquefy and then make good aerosols

Typhoid Fever (21st century perspective) - symptoms

-headache, malaise (feeling bad), fever -constipation, sometimes no diarrhea -later, rash on belly and chest, distended abdomen, tenderness, enlarged spleen -white cell count decreases -sometimes delirium, perforation of bowel, pneumonia -slower onset - lasts for a month -requires treatment

Sources of TB disease

-infection and progression to disease -reactivation of latent TB -cf shingles and chickenpox -reinfection with TB

Bubonic Epidemiology

-infection endemic in rodents (but established so does not kill them all) -fleas bite and drink blood (with bacteria) -bacteria adapt to survival in flea cooler, etc. -lose virulence factors for humans -if no rats, fleas bite humans

Pre-history of TB

-may have had sporadic origins by mutation from animal strains of Mycobacterium -not endemic until the rise of agriculture (ca. 8,000 BC) -Requires communities of 200-400 persons or it dies out -Epidemics require higher densities still, and travel

Treatment for bubonic plague

-modern antibiotics make it easy to treat if identified early -pneumonic is particularly difficult because patient often dies before diagnosis! -without antibiotics, no treatment mortality varies from 30 to 70% or more

S. typhi

-no good animal model - only in humans -we know surprisingly little about it -stomach to blood (floats everywhere) to intestines (not the direct route like enterica)

Three basic forms of life

1) Bacteria -Germs and decomposers 2) Archaea - less well know -- usually in extreme places 3) Eukarya -plants, animals, algae, fungi, amebas, etc.. * all have a common ancestor

Mary Mallon' s Options

1) Stop cooking: She tried. How to make a living? 2) Have her gall bladder removed -risk of surgery in 1907- by 1914, 5 other carriers had theirs removed -- no effect 3) Laxatives and diuretics no effect and not very pleasant

Tragic story of the Bronte family

1821: Mother died of TB after birth of 6th child 1825: Maria (eldest) developed symptoms and died at age 12 1825: Elizabeth returned 1 month later and died 1 month after that at age 11 1848: Branwell (opium addicted poet) died of TB at age 31 1848: Emily (Wuthering Heights) came to the funeral, "caught cold" and dies in December of "galloping consumption" at age 30 1849: Anne (Agnes Grey) died of TB (age 29 1855: Charlotte (Jane Eyre) carried a chronic form of fibrotic TB that occasionally flared up; "caught cold" and developed active TB and died at age 39

Robert Koch

1882, identified the tubercle bacillus using fuchsin (German chemical industry and fabric dyes) boil in acid and cells retain fuchsin other stains don't stain Mycobacterium other bacteria are bleached by the harsh treatment grew it in pure culture on solid medium not so for M. leprae which still requires armadillo footpad culture

Koch and Pasteur

= Confidence. Rabies Tuberculosis Anthrax Cholera (John Snow in 1830's)

Global Burden of TB (2013)

About 1/3 of all humans are infected (Lifetime risk of progressing to illness about 10%) In 2013, 9 million fell ill with Tuberculosis (includes 1.1 million living with HIV) In 2013, 1.5 million died (includes 360,000 living with HIV) Leading killer of those with HIV about 1/5 of all HIV deaths globally -expect about 9 million new cases a year -About half a million MDR-TB -expect about 1.5 million deaths per year -About 200,000 MDR-TB the leading cause of death from infectious disease in the world after HIV/AIDS!

Effect of plague on Jews

Accused of poisoning wells -Pope Clement VI came to their aid -Masses rejected physicians and popes -- took things into their own hands Strasbourg govt. protected Jews -deposed by masses -new govt. burned 900 Jews (50% of the Jewish community there!)

Multidrug therapy for TB

Almost completely effective, but can take a long time after symptoms go away now there are drug resistant forms of TB Monotherapy and the effects of mutation Evolution Need for multiple drugs at once Lesson for HIV treatment Why does single drug work for some other infections?

Typhoid Mary

An immigrant, Irish woman who made her way as a cook (born 1869), was well liked and respected. Probably exposed to typhoid fever around 1900- Between 1900 and 1907, she infected 22 people with typhoid fever; one died. She was quarantined on North Brother Island (aged 37) for three years. She claims she was never actually sick - but she was sheding. Released by new health officer and promised never to cook Eventually found at Sloan hospital cooking for the staff(changed her name- Mary Brown), at least 25 more people infected, two more deaths. Returned to North Brother island for the rest of her life. Died of a stroke 23 years later

Antibiotics

Antibiotics (should) kill bacteria. *Many are naturally occuring from other bacteria or fungi *Take advantage of pathways or structures that are unique to bacteria - Cell walls -Protein or DNA synthesis machinery *Came into common use during and after World War II (esp. after 1950) They come from bacteria. Chemists tinker with them. They take advantage of the differences between bacteria and humans No new antibiotics in he last 20 yrs - scary Antibiotics or sanitation caused the rapid decrease in deaths from infection disease?: Antibiotics came into use in early 1950s - deaths were significantly decreasing well before the medical breakthrough so its silly to say that antibiotics did this.

Human Anthrax (modern)

Before 2002: Antibiotic treatment effective 90% for skin anthrax But only 10% for inhalation anthrax (antibiotics worked but not fast enough) After 2002: Almost 100% effective for skin anthrax About 50% for inhalation anthrax

Gastroenteric upset

Caused by salmonella. rapid onset some fever, diarrhea and vomiting, usually straight through and over in a day or two, "Stomach flu"

Mary Mallon the person: Her legacy

Change in the story since her death. *1950-1970, almost uniformly negative -triumph of modern bacteriology and science antibiotics, implicit trust in governmental science -after 1980, more complex views, post AIDS or post Vietnam? *Modern Issues raised by Mary Mallon's story -Identification and labeling: not neutral, marginalized to start with, power relations -Isolation as solution: Huge power in Public Health officer, Care of sick vs. protection of uninfected, which is primary?. Cuban AIDS solution, Ebola questions -Blame and responsibility: scapegoating, immigrant and marginalized communities, alternatives: what if they retrained Mary? they did later (on the island), they did for some others What should we isolate What should we protect against? -Moral threats? (religious threats) -Political threats? (ideologies) -Cultural threats? (TV and pornography) -Does it depend on the era?

1894: The Plague that Almost Was

Chinese Expansion of 1850's . Troops sent to China/Burma/India region of Himalayan foothills -plague has been endemic there for centuries - locals have customs that prevent its spread -troops did not know these customs Plague spread through parts of China Reached Canton and Hong Kong by 1894 China and the Europeans European "concessions" after the Opium War Threat to European trade Spread by steam ship to European, American, and Indian ports Rapid quarantine measures

Diarrhea

Chlorea. -Happens early on, fecal and malodorous (smell) -later "rice water stool" (after there is no feces left) -painless -non-straining -sometimes a little cramping (like an enema) -Massive

Hamburg 1892

Cholera Outbreak. *Hanseatic State (independent city-state that depend on trade) *Oligarchic rule (Senate) *No civil service *Capitalism (Trade) rules all ---- Filtration of water - known to be effective since John Snow - costs money, so delayed - Altona (downstream and next to Hamburg) had filtration -Altona had significantly fewer deaths because of filtration system ---- The Hamburg-America Line transporting immigrants to America especially from central and eastern Europe A trainload of immigrants from Ukraine : -Known cholera outbreak -Hamburg accepted them anyhow -Cholera broke out in the warehouse where they were kept -Shipped them to America Cholera ships : -shipowners feared closing the port of Hamburg -Medical officer forced American vice-consul to give clean bill of health to ships -Several ships forced to sail back to Hamburg -Many deaths -Slow action on an epidemic cost thousands of lives.

Outbreak at the Broad Street Pump

Cholera. -London 1854 -"Worst outbreak ever" -over 500 fatal cases within 250 yards of the pump -a few cases in late August - Probably originally came in from the Black Sea Fleet -Really began the night of Aug. 31/Sep. 1 Actual Cause of Outbreak? - Learned by the clergyman (Henry Whitehead) after the fact - Infant developed diarrhea on Aug 28 (died Sept. 2) - Mother (Sarah Lewis) soaked diapers in pails - Emptied pails into cesspool 3 feet from broad street pump that was leaking. The first week (ending Sept 2) 83 cases: - all but ten were nearer the Broad St. Pump than any other -5 families said they preferred the water from the Broad St. Pump - 3 were children who went to school near the pump - 2 occurred before the real outbreak - The majority of cases lived near the pump: -61 known to drink from the pump -6 no info (whole family died) -6 did NOT drink from the pump directly may have drunk indirectly, water in drinks (liquor) or sodas Pump handle removed on Sept 8: - Board of Guardians of St. James' parish on the 7th - ended the outbreak (as did the departure of 3/4 of the residents!) - Pump water was probably already cleared of cholera by then anyhow - But the pump handle makes a more dramatic story Added twist: *Baby Lewis died on Sept. 2 ending in contamination of the pump well *Thomas Lewis (father) fell ill on Sept. 8 - Same day the pumphandle was removed *Removing pump handle did not end the outbreak, but it did prevent a second wave. *(No other apartment in the house had access to the old cesspool) Lessons from the Broad Street Pump: - Almost everyone who died drank from the pump - No question: cholera is transmitted in the water. Period. - But the official report still attributed the cause to a miasma Why did John Snow suspect water as the source? Early Outbreaks: -Southwark and Vauxhall Water Co. dirty -Lambeth Water Co. dirty - Cholera about the same for both -Chelsea Water Works, clean much less cholera Outbreak of Aug 1853-Jan 1854: -Lambeth found new source of water upstream of London's sewage outlet - Some districts purely Southwark and Vauxhall, some purely Lambeth - Some districts had BOTH sets of pipes on the same street! -Most deaths involved S & V company, much fewer deaths with lambeth -S&V water had 37.9 grains of salt per gallon -Lambeth water had 0.95 grains of salt per gallon -easy to tell apart -Vibrio cholerae requires some salt for survival -Lambeth, clean; S&V, dirty

Spores of anthrax

Designed for survival Non-growing (dormant) state Very little water Hard outer shell Smaller than growing cells If a cell is a cocktail sausage, a spore is a marble Very resistance British germ warfare experiment 1942 Gruinard Island (Coast of Scotland) Spores active for decades - sheep from grazing Decontaminated by spraying 280 tons of formaldehyde diluted in 2000 tons of seawater (1986 -- declared "safe" in 1990) Spores are known to be active even 100 years later! (medieval hospital site) Tried it out - World War 2, in case they had to use it against germans

TB and HIV

Faster development -HIV+: 2-10/100 infected with TB get TB disease -HIV-: 10-20/100,000 infected with TB get TB disease *about 1/3 of the TB in recent years is associated with HIV in the US * about ¼ is from communal living conditions such as prisons, shelters, and even hospitals) --- *33 million people are HIV+ *more than 14 million of those are also TB+ -In Africa, 40% or more of all TB patients are HIV+ *AIDS speeds progression from latent to active TB *AIDS does not increase transmission rate -mostly non-pulmonary (non-infectious) -die faster with less time for transmission

Conquest of Anthrax

Fathers of microbiology Robert Koch (started as country doctor) -Identified bacillus -- first one ever -Basic science approach Louis Pasteur (started as a chemist/inventor) -Made vaccine *"attenuated strain" - things that have grown and no longer pathogenic -Not a physician

Numerical Effects of Plague

First wave killed at least one third of Europe Later waves probably killed almost another third Result was loss of about 50% in population Not every place was the same

Salmonella enterica Process

Food poisoning. Normal process. Phagocyte consumes bacterium but leaves space (vesicle) around the bacterium so it's technically both inside and outside of the phagocyte. The Bacterium thinks it's outside. Lysosome (digestive bodies) travel to the vesicle containing bacterium and digests it

TB in the Pacific islands

Hawaii: rare or absent as late as the 1850's New Guinea: absent until 1951 then symptoms were "typhoidal" as expected for a naive population

Mongol Siege of Kaffa in the Crimea (1346)

History of the Black death Kaffa was Genoese colony (Italian) Plague reached the Mongol armies Threw bodies into the city to spread disease before abandoning the siege Europeans inside fled the city by ship back to Mediterranean ports -Marched across Europe within two years

TB and the Angelic Death

Immigrants, thus dirty and ignoble Nobility too, so maybe OK Slow, lingering, time to philosophize La Boheme, La Traviata and others Need to come to terms with the dying No operas about Cholera!

Long term effects of Plague

In general, realization that authority could not protect, so anarchy cf. Ryan White story and AIDS Poorly trained administrators and clerics Ill-equipped to handle later waves of plague General collapse of authority structures church and feudal structures

Typhoid Mary: Legal Issues (general overview of ways of thinking at the time)

Infected = Sick (legal issue) Infected = dangerous? sick = dangerous only because of contagion(the communication of disease from one person to another by close contact) Thus, fear of contagion is the basis for the laws Generally: is fear the basis for law? What about "exposed?" (Ebola? HIV?) Questionable equivalencies: sick = contagious infected = sick (Basis for isolation of Mary Mallon) (Questionable legality cf. pneumonia germs (we're all carriers!) (Think Ebola?) infected = contagious (Basis for quarantine -What about families that she did NOT infect? -Other sources of typhoid were greater - Broke new ground in US law *Big Issue in 1907 was predictability: Would Mary Mallon stop cooking? Was isolation a "last resort?" Rosenau and Chapin thought NYC was embarrassing itself. After 1915, maybe different, but in 1907...? * Summary: How big was the threat Was isolation the only alternative Was it legal -- was it moral Why did it happen How did they get away with it

The Public Health Trackers of plague

Koch and Pasteur sent proteges Yersin (Pasteur) and Kitasato (Koch; indep.) simultaneously found the organism Quickly made the connection to fleas Fast action by international rules on quarantine, fumigation, etc. ended the threat But.................

Tuberculin skin test

Koch thought it was a vaccine. Wrong For populations that have not been vaccinated with BCG, it tells exposed or not if you have antibodies, you react, if you've never seen M. tuberculosis you don't -Widely used in the US to screen for TB Note: only 3-5% of tuberculin positive get TB disease

Robert Koch (anthrax)

Koch's postulates -Germ present in all with disease and none without -Germ grown in culture causes disease -Germ isolated from inoculated (and diseased) causes disease in another Father of microbiology

Economic Effects of the Plague

Land used for pasture not just cereal crops Mills used for manufacture not just flour General inflation lasted till 1370 or even 1390 Labor Shortage -Fall in land rents, refusal to work worst lands -"Factor Substitution": cheap land and capital, expensive labor, wool replaces wheat, oxen for farmers, technology to increase productivity -Increased living standard for lower orders "Sumptuary Laws" (an aside) *tried to regulate presumptuousness of lower orders -limited their dress, food, socializing "beyond their station" *The number of such laws suggests that they were not effective *This is the rise of the bourgeoisie, the middle class Net Effect -more diversified economy -more intensive use of capital -more powerful technology valued -higher standard of living -in short, Western Democratic Civilization as we know it!

Anthrax = effective weapons

Large spores (or clumps) ineffective Filtered by nose and throat Expelled by mucus escalator and ciliary sweeping Small spores (round smooth shape) Trapped in small sacs in lungs Grow and develop

Public Health and the Conquest of TB

Laws against spitting cultural change end of spittoons proscription of against spitting Sanatoria and confinement Infection leads to immunity

Rise of local Universities (After plague)

Lots of benefices from so many dead Need for more trainees plus fear of travel led to local foundations Rise of regional and national learning centers led to a loss of international unity Good preparation for the great political and religions schisms (e.g. the Reformation)

Why so stubborn (Mary vs. Authorities)

MARY: - The Irish Question The contradictions -two world views -inconsistent stool results -her own lab results -First contact -Culture clash AUTHORITIS: -Soper had the first US carrier -New York had one of the first municipal bacteriology labs - She was a perfect "longitudinal study" - "She never would be missed" -Irish, woman, unmarried, lower-class - Culture clash

Nature of Courts in 1907

More "state" oriented Individualism less an issue no such thing as "privacy" Guardian of status quo

Tuberculosis

Mycobacterium tuberculosis. About 1/3 of the world population has latent tuberculosis! -tuberculin test measures infection, not disease TB has many forms (many names): *Phthisis ("wasting away") Hippocrates *Scrofula (swollen glands of the neck) -"Kings Evil" -- cured by the touch of kings *Lupus vulgaris (TB of the skin) *Pott's Disease (vertebral fusion and deformity of the spine) - visible in skeletal remains (mummies from 2000 to 4000 BC) *Consumption (TB of the lungs)

Political effects of the plague

New Economic System -Towns abandoned -Jobs left undone, by death or flight, just "who cares? Tomorrow we may die!" -increase in demand for skilled (physicians, priests) and unskilled (gravediggers) labor more opportunities, fewer qualified, few masters to train all the apprentices -rising status of women: allowed to be witnesses in court, allowed to hear The Malthusian Deadlock -Europe quite stable, but no progress possible (famine and prices balanced growth and birth) The Plague broke that deadlock

Salmonella in general

Nomenclature problems. Facultative aerobe (Can live with air/anaerobe (can live without air) - can live everywhere

Transmission of TB

Not very infectious, but very serious Main route is breathing controversial as late as 1955 or 1960! 1 sneeze = more than 1,000,000 droplets with 3-10 bacilli per droplet air from a TB ward can infect guinea pigs (UV treated air does not)

Plague Spread through North America

Now endemic in Western US, Canada, and Mexico Spread was slow and probably directly from rodent to rodent Humans can speed the progress (because of transportation)

Septicemia plague

invasion of bloodstream death within 24-36 hours 100% fatal (one of 3 forms of plague)

John Snow

On the Mode of Communication of Cholera by John Snow, M.D. Second edition, much enlarged 1855 (preface dated 11 December 1854) Biography: British surgeon, Pioneer anesthetist, Chloroform for Queen Victoria (1853) birth of prince Leopold, Published a research monograph on either in 1847 Suspected water was the source of spreading chlorea - Broad street pump outbreak --- Importance of Snow's work -Miasmatists used his spot map to support their own (less specific) theories -General sanitation vs. specific cause -Not really recognized until much later - Now he is "myth" and parish committee is forgotten, especially Henry Whitehead -?Myth?

Equal treatment under the law? Typhoid Mary

Other carriers: -Tony Labella: 87 cases, 2 deaths in NYC fled to NJ from NYC in 1922 -35 more cases, 3 deaths- not isolated - Alphonse Cotils: A listed carrier in 1924 found be working in his restaurant - suspended sentence -"can't lock a man away just because he's unlucky enough to carry some germs" -"Typhoid John": Adirondack guide, Infected 38, 2 of whom died. (more than Mary Mallon at that time), Judge let him go, Newspaper dubbed him Typhoid John, Obviously know of Typhoid Mary. Judge of John: "there was no State law by which a human carrier of typhoid bacilli could be kept from spreading contagion and disease" NY Times: "there is no law in this country restraining the movements of these human carriers of typhoid germs, although medical experts estimate that there are probably some 10,000 such afflicted persons in the United States" *Another issue is detection: Tyranny of "zero tolerance" when detection limits change. Who knew that Mary Mallon was not the only carrier in New York? The Public Health Department? The Judge? Her Lawyer? Today: radon, anthrax, carcinogens, etc. TIME Magazine article on Risks: real and perceived * How we react today: -Tuberculosis-HIV/AIDS- The unknown: Ebola, Enterovirus D68

Finding Carriers of Typhoid

PROBLEMS: Typhoid was "reportable" but problems with physicians: stigma, loss of work and patients, opposition to state medicine 3 WAYS TO FIND: *Track every case bacteriologically until clear -never more than 10 or 20% effective * Screen all food personnel -expensive (more later, Syphilis) - problems with private physicians *Epidemiological tracking : finds the important carriers, lets the "unimportant" carriers alone, only useful AFTER an outbreak, does carrier = infectious? does carrier= dangerous?

New Catholic movements (plague)

Paradox of pilgrimage -flee plague, get grace, transmit plague -end of hospitality as towns bar the gates Clement VI give plenary indulgence for pilgrimage to Rome in 1348! -1350 is made Jubilee Year -200,000-a million pilgrims in Rome on any given day Flagellanti Pope tried to suppress them but failed Lots of superstition and excess Confusion with Inquisition

Salmonella Typhi

Phagocyte consumes bacterium but leaves space (vesicle) around the bacterium so it's technically both inside and outside of the phagocyte. The Bacterium thinks it's outside. When lysosome goes to digest it, there is not fusion and Salmonilla keeps growing until they escape the phagocyte *Salmonella typhi does something to the vacuole (don't know what) *Lysosomes cannot fuse with the vacuole *Thus S. typhi not killed *Thus S. typhi GROW in the cell that is supposed to kill them! Phagocytes that carry S. typhi eventually die and release bacteria -Dead cells not good for body - Infected cells go places where S. typhi would not be welcome (immune surveillance) -NOTE: Cells inside a vacuole are hidden from the blood and its factors.

Immune response

Primed and unprimed If primed, effect is immediate If unprimed, takes 10-14 days to get it up and running PRIMED IMMUNITY: *Body saw invader before and stockpiles weapons *Analogy: proper antidote to a poison *Two forms 1) blood is full of antibodies (recognize invaders and coat them with stuff) -2) cells have antibodies on surface and go bonkers when they recognize invaders UNPRIMED IMMUNITY: - First have to recognize invader as "not self" -Then have to build a recognition system for defense -Then have to build the specific defense -Then can wipe out the invader -VERY POWERFUL effect, almost always successful, but it takes 10-14 days -- maybe too long!

Health and Disease in 1900

Related to Typhoid Fever -Infectious disease is the major cause of death -Epidemic (outbreaks) vs. endemic disease -Miasmas (bad air) vs. germs: good food, good air, good exercise. The success of sanitary engineering - lifespan doubled - not medicine that was the big changer but sanitation created by civil engineers

Anti-contagionism

Related to cholera and the Hamburg ship outbreak. -Pettenkofer and conservatism of physicians (could not culture bacteria or use microscope) -Koch was Prussia -Anti-contagionism was more "intuitive" and cheaper!

Importance of the Plague

Rise of capitalism and Protestantism in Europe Rise of cities, food surplus, and industry Anarchy leading to "democracy" in the West End of the "cyclic view" of history

Pneumonic Plague

Same as Bubonic, but spread by aerosols (sneezing, coughing, even talking) "Ring around the Rosie" Very fast acting 100% fatal About 5% of bubonic victims become pneumonic

Mary Mallon the person: her life

She was a domestic servant -- harsh life. treated like children (condescending), treated like slaves, long hours (early AM to late eve), easily replaced but not easy to find new jobs, Trapped:no time to hunt for jobs or husbands, no place to live between jobs, upstairs-downstairs- religion, class- at least factories were inspected, she had grounds for suspicion - Persecuted?: She had never heard of healthy carriers, Scapegoating, Surgery: "they are trying to kill me" - Returned to cooking. Why? : Used to make twice the avg. domestic's salary ($45/month), love of her life Mr. Briehof died in 1913, No other good jobs. When did she start cooking again: Soper said "immediately." First documented in 1914 Certainly not before 1912 (health dept. followed her that long) - On the island for life: seemed to adapt, series of jobs several friends, just don't mention typhoid, never trusted doctors (or dentists) - What IS the evidence that she CAUSED typhoid fever in anyone?: Statistical, Circumstantial, Would you believe it today?

Short term effects of the Plague

Social dislocation -tensions between healthy/sick, mainstream/marginalized, masses/leaders Death rituals abandoned -Boards of health = death sentence = no Christian burial -Even the Church suspended rules for burial

Multiple Drug Resistance

Source assumed to be non-compliance Often traced to a single source -frequently in hospital Treatment same as the old days (sanatoria) Need for vigilance and quarantine -back to Typhoid Mary

Chopin

TB *Went to Majorca to relieve TB symptoms with George Sand (his mistress) good film *Town drove them out Landlord wanted reimbursement for replastering Carriage drivers would carry them or their goods -Crossed the island with wheelbarrows -Sailed to Barcelona with a load of pigs Innkeeper in Barcelona charged them for the bed (which the authorities burned) Died in 1849, at age 39

Acid Fast stain

TB Erlich (in Koch's audience) improved the stain -- later used it to confirm his own TB diagnosis Ziehl and Neelson improved it yet more Ziehl-Neelson is still used to stain sputum smears

John Keats

TB story - not so bleak mother died when Keats was 14, brother too diagnosed in 1820, died in 1821 at age 26 he swam the Hellespont! No weakling.

BCG (Bacille Calmette and Guerin)

TB vaccine late 1890's, knew of "attenuated" vaccine (rabies) tried one with long-term cultures of M. bovis between 1908 and 1919 (seemed to work then) Clinical success is still in dispute. Widespread use, but not in US Destroys utility of tuberculin skin test -Should BCG be Used?: A good example of two different approaches to Public Health -- most widely used ever about 100 million per year, 3 billion total safe efficacy ranges from a few % to 95% declines in BCG countries (UK, Sweden) no greater than non BCG countries (Netherlands) why the variations?

Bubonic Plague

The Black Death Yersinia pestis -caused by Yersinia pestis -transmitted by flea bites -infected reservoir is various rodents Probably began in China in 1331 Role of Mongol trade routes -brought it across Asia and into rodents The disease -flea bites, then 2-8 days, fever of 105 -2-3 days later, buboes (glands close to bite) -burst and suppurate, red spots on skin -8-10 days later, convalescence (if not dead) -mortality about 30-70% After the flea bites - bacteria in blood, filtered out into lymph nodes (hence buboes) -survive inside some white blood cells -eventually break out and into bloodstream -endotoxin causes shock -may get to lungs -get to all tissues

Typhoid Mary Full Story.

The Oyster Bay Outbreak (1906): -6/11 members of the Warren household (3 family and 3 staff) had typhoid fever -The landlord hired George Soper (civil engineer) to find the source worried about being able to rent the place! -Ruled out all the usual sources food, well water, barn even clams from the bay -Mary Mallon Suspected-Soper knew about "healthy carriers" from the German medical journals -He traced her former employment (though the agency) and found a record of typhoid outbreaks. She always left soon after. 26 infected total (why so few? immune?) Wanted stool, blood, and urine samples to be sure George Soper "visits" Mary Mallon -He appeared unannounced and tells her she is spreading typhoid fever - He wants her to go to the hospital and give him a stool, urine, and blood sample -She throws him out of the house He tries again bringing a doctor- She throws him out again. Soper convinces the health dept. that Mary is a likely carrier - Hermann Biggs sends Josephine Baker who calls in the police - Mary escapes and her neighbors hide her - Mary dragged away to the Willard Parker Hospital for contagious diseases and samples taken by force - Found typhoid bacilli (Salmonella typhi) found in her stool

Three European Visits - Bubonic plague

The Plague of Justinian (mid 500's) The black death (1346ff) The plague that almost was (1894)

Loosing the Battle against TB

The glory days -Since 1939, isolation, sanatoria, and hygiene led to a steady reduction in cases -pre-chemotherapy! Case reporting since 1953 (post drug) showed a steady 5% per year decline till 1984 1985-1992, a steady increase (3%) -immigration from places with high TB -AIDS -Collapse and Abandonment of Public Health -measures - government budget cuts -as many as 90% of patients discharged, stopped taking their antibiotics -"civil liberties" -Re-application of "Directly-observed Therapy"

Pathology of Anthrax

Three routes of infection for humans 1) Skin contact (scratches) 2) Ingestion (eating) -- rare in developed world Eating undercooked meat from infected animals 3) Inhalation (breathing) Inhalation and ingestion are the worst (will kill you)

Robert Louis Stevenson

Traveled widely for his TB (sanatoria) Died in old age of vascular disease unrelated to TB

Mary Mallon- Gender Issues

UNMARRIED no man to "control" her no family to enforce health restrictions questionable moral code lived in apt. of a man (and a dirty one at that!) rebel or "something" must be wrong valid arguments? WOMAN expect docile and submissive expect suffering not a breadwinner or a "career" -contrast with Josephine Baker DID IT MATTER? descriptions of Mary Mallon: walked like a man, used strong language, females cooked, males did not (?!) no family ties, nobody to control her, nobody to defend her, job options FEMALE CARRIERS (later) - most on the list were female - more dangerous because of cooking -rules included wives, women over 40, grandmothers, mothers-in-law, etc.

TB in Europe

Virulent but unimportant until feudalism By early 1600's, rising in England by 1800's almost all West Europeans were infected Eastern Europe (Russia) mostly free until 1880 or so

The plague of Justinian

Well documented in mid 500's huge losses in population end of the Western empire no mention of it after 767 Why did it die out? -population too small? -no good rodent population -black rats did not get to Europe until later -transport too slow But still existed elsewhere

Phagocytes

White blood cells *Engulf and eat bacteria and viruses -like amebas *Encases bacterium in a sac (vesicle or vacuole) *Other sacs (vesicles) called Lysosomes fuse -Lyso=dissolve, some/soma = body *Bacteria digested ___ *Inside of the vacuole (where the bacterium ends up) is the same as outside the cell *Imagine a cell that excretes digestive juices *Bacteria and viruses not always digested all the way to foodstuffs *Sometimes it just goes to little pieces -important later for immune response

Bad germs

Who defines "pathogen? Few pathogens Many pathogens are ill-adapted

Her own bacteriological tests *Mary

Why were they negative Why were they discounted Why did she have them done

plague & Establishment in the US

by 1900 some cases of Plague in US soon it became established in the rodent population of the West (prairie dogs, ground squirrels, etc.) all "new" species for plague many different species of flea very versatile pathogen

Chlorea- clinical features

diarrhea vomiting (early) Dehydration * death

Bacterial size

variety, but typical ca. 1µm long 1µm = 10-6m = 0.000004inches 25,400 end to end per inch! feces is ca. 50% bacteria ca. 10,000,000,000 bacteria per gram (sugar cube size)