SAS 013 001 Final Exam

Quarantine

• Separation/movement restriction of individuals exposed to a contagious disease who are not (yet) sick

• One can be exposed to it, but never get the disease

quaranta giorni

an Italian term that created “Quarantine,” which means forty days

Yellow Jack

• a flag that represents quarantine (ex. first practice was during Black Death in 14th century

Wilbur Wright

• one of the Wright brothers who created the first functional airplane that flew first flight ever on December 17, 1903

• Died May 30, 1912 of typhoid fever from contaminated food

Orville Wright

one of the Weight brothers who had typhoid fever in 1896 but recovered

Leland Stanford Jr.

• son of Leland Stanford Sr.

• Died of typhoid fever in 1884 at the age of 15

• was the namesake for "Leland Stanford Junior University" —> Stanford University today

Leland Stanford Sr.

• 8th Governor of CA U.S. Senator

• Was a big part of Southern Pacific Rail Road, CA

• Founded Stanford University in memory of his only child, Stanford Jr.

Karl Joseph Eberth

discovered the bacteria Salmonella enterica serotype Typhi (Salmonella Typhi) in the abdominal lymph nodes and the spleen of typhoid victims

Typhoid fever

• Humans are the only host of this disease

• Incubation period 6-30 days

  • (Week 1) —> low fever, dry cough, headache, fatigue

  • (Week 2) —> high fever, bradycardia, rash, spleen enlargement

  • (Week 3) —> high fever, weight loss, pneumonia

Typhoid fever

• Salmonella bacteria can invade through M-cells, Peyer patches (part of GI tract) and seep through lymph system and blood stream (get inside immune cells like macrophages)

• May persist in lymph nodes, bone marrow, and spleen for life

• Bacteria can be shed in stools

How is typhoid fever spread?

• Salmonella bacteria is spread via contaminated food and water (Fecal-oral route of transmission)

• Mostly affects areas with bad sanitation (WASH prevention is needed to reduce this) —> can contaminate soil, wells, and other water sources

Mary Mallon

• Immigrated to U.S from Ireland in 1883/1884 and worked as a cook in New York city for wealthy families

• Affected nearly all of those wealthy families with typhoid fever

• “healthy carrier” of Salmonella Typhi in U.S. (gallbladder was infected with S. Typhi)

• Claimed she never had typhoid fever, was arrested, and sentenced to quarantine on North Brother Island for three years

George Soper

• sanitation engineer that was hired to investigate Mary Mallon’s case, what caused the typhoid outbreak in these wealthy families?

• accused Mary Mallon because she was a “public health threat”

What happened after Mary Mallon was released from quarantine?

• Promised to no longer work as a cook

• Worked as a laundress in mainland, but pay was too low so she made a fake name Mary Brown and became a cook again

• Caused more deaths when working at Sloane Maternity Hospital of Manhattan

• Quarantined for life, suffered a stroke in 1932, lost the ability to walk, and died of pneumonia in 1938

• Autopsy (possibly) showed live bacteria in gallbladder

Stigma

• word of Greek/Latin origin: “a mark/brand (tattoo) made with a pointed stick”

• Slaves were marked and punished in ancient Greece and Rome (ex. Scarlet Letter, wearing yellow star to be a “stigmatized individual”)

Stigmatization

• characterized by social and physical avoidance of a person(s) by other people

• factors of stigma —> visible/contagious, visible/non-contagious, label/non-contagious

Stigma - visible/non-contagious

Having any “visible” signs on the face is the most important part for developing stigmatization

Stigma - visible/non-contagious

even if disease is non-contagious, stigmatization can still occur if the signs are visible either way

Stigma - label/contagious

• HIV/AIDS

• spread through bodily fluids, but there is still prejudice when someone has HIV/AIDS due to a “label”

Stigma - label/non-contagious

• Ebola (can only spread through bodily fluids like HIV)

• Those who survived ebola are no longer contagious, but they are still ostracized from society, children of these survivors are affected

Hansen’s Disease (leprosy)

• chronic bacteria infection caused by Mycobacterium leprae

• leper comes from term ‘lepros’ which means 'scaly’

• Least contagious of all communicable diseases, but noted as highly contagious over centuries

• long incubation period

• close contact with people to spread this disease

Effect on body from Hansen’s Disease (leprosy)

• Mycobacterium leprae grows very slow and best at colder temperatures (grows on human skin, mouse footpads, armadillos)

Symptoms of Hansen’s Disease (leprosy)

• loss of sensation

• deformities

• red skin patches

• bacteria in slit-skin smear presented under microscope

• Mainly affects skin, peripheral nerves, and nasal mucosa

• replicate in macrophages (skin) and Schwann cells (surrounds ‘swelling’ peripheral neurons)

Paucibacillary (PB) case

• 1 to 5 skin lesions

• no presence of bacteria in a skin smear

Multibacillary (MB) case

• more than 5 skin lesion

• presence of bacteria in a skin smear

Daniel Danielson

‘father of leprology’ who believed leprosy was a hereditary disease

Gerhard Henrik Armauer Hansen

• was convinced that leprosy was caused by a bacterium

• saw rod-shaped bodies on biopsies of skin nodules of patients, but didn’t wanna assume its bacteria

• Was not able to culture in artificial medium or inoculate an animal model (could not satisfy Koch’s postulates)

• Attempted to inoculate patient without her consent and lost his job at hospital

• led to a suggestion that it may be caused by bacteria

Leprosy used to be known as…

elephantiasis Graecorum by Galen.

mai ho’okawale

• separating sickness (Molokai, Hawaii)

• the main leprosy hospitals and isolation was in Hawaii and Louisiana

19th century Louisiana: ‘la maladie que tu nommes

pas’ means…

the disease you do not name

The name Hansen’s disease was adopted in…

1948 by US Public Health Service

Where did Hansen work?

Norway National Leprosarium #1, which is a hospital for the treatment of leprosy on the island of Spinalonga, Crete

Leper colonies/houses

• were Christian-run and also known as ‘lazarettes’ or ‘Lazar houses’ after Lazarus (patron saint of people affected with leprosy)

• Bell and clappers were enforced to indicate that affected people were approaching

What did WHO suggested about Hansen’s Disease?

recommends the abolition of compulsory isolation of those with leprosy in 1960

Kalaupapa peninsula (site for isolation colony)

was designated by the Hawaiian Kingdom for people with Hansen’s disease in 1866

What was the Hawaiian isolation law that lasted until 1969?

it required the isolation of people with Hansen’s disease, forced them to go to Kalaupapa peninsula in Hawaii

Carville, Louisiana

• the only national leprosarium in the continental U.S.

• “U.S. Marine Hospital No. 66” (1921) but later name changed to “Gillis W. Long Hansen’s Disease Center” (1986)

  • delay in establishing the Leprosarium due to WW1

Daughters of Charity of St. Vincent de Paul

Order of Catholic sisters provided nursing care in leprosarium at Carville (1896-2005)

Rules of Carville for those with Hansen’s Disease

• patients encouraged to change their names so stigma will not associate with their family

• married patients could not live with non-patient spouses

• children of patients cannot live on site

• marriages between patients not allowed until 1950s

• could not vote until 1949

• outgoing mail was “sterilized”

Public Health Service Leper

a certificate that stated the reason for discharge from Carville (‘no longer a menace to public health’)

Stanley Stein

one of the patients affected with Hansen’s disease (leprosy) that raised awareness about the disease in the Star newspaper

Other aspects in the history of leprosy

• the name ‘leprosy’ was changed to ‘Hansen’s disease’

• Reconstructive surgery (limbs affected were constructed)

chaulmoogra oil

was first used in the early 20th century for Hansen’s disease (came from seeds of Hydnocarpus wightianus and was painful)

Dr. Guy Henry Faget

• officer of U.S. Public Health Service who studied promin for Hansen’s Disease in relation to mice

• Promin was a sulfone drug (‘Miracle of Carville’) in 1941 —> volunteers took these painful injections

Dapsone pills

another type of medication for leprosy for bacterial resistance

What does WHO suggest for the treatment of leprosy?

• multidrug therapy (MDT): dapsone, rifampicin, and clofazimine for 6-12 months

• note that rifampicin is also used for tuberculosis

Current cases for leprosy

• no highly effective vaccine used for it

• BCG (treatment for tuberculosis) is used for this disease as well

• a widespread use of MDT reduced the burden of leprosy

Guinea pig (Cavia porcellus)

metaphor for a subject of scientific experimentation, used by scientists since the 17th century

Robert Koch

inoculated guinea pigs with tubercle bacillus (TB bacteria) —> guinea pigs are susceptible to it

Marcello Malpighi

Italian scientist who played a part in vivisection and anatomy of guinea pigs

Duncan-Hartley guinea pig

• bred specifically for lab work —> used mostly in labs related to allergies, nutrition, hearing, safety testing (vitamin c and study of scurvy was discovered from this pig)

• like humans, these guinea pigs cannot synthesize own vitamin C

• today, most are replaced by mice and rodents

Ethics of lab animal testing

Three Rs
- Replacement: Avoid animal models

when possible (use non-animal

models)
- Reduction: Design experiments to

use the minimum number of animals
- Refinement: Improve methods to

reduce animal pain or suffering

“Professional” guinea pigs (Guinea Pig Zero)

• a novel that talks about volunteer medical research subjects who participated in clinical trials where drugs are tested on them

• concerns about exploitation

• individuals that might not be good financially would feel that this is the best way to make money so they donate their body to science in a bad way

Placebo

An inactive substance or other intervention that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or other intervention are compared to the effects of the placebo.

placebo response

the measured response of subjects to a placebo

placebo effect

the difference between that response and no treatment

drug effect

the response obtained with the drug minus the placebo

response

placebo group

given an inert pill, and told that it is in fact inert

Dachau hypothermia experiments

• medical torture during the Holocaust

• there were debates on whether these experiments should be credited or not

The Nuremberg Code

involves ethical research principles for human experimentation

The Tuskegee Syphilis Study

• unethical human research that took place for 40 years

• studied by the U.S. Public Health Service and Tuskegee University in Macon County, Alabama

• Studied natural progression of untreated syphilis

syphilis

sexually transmitted infection caused by the bacterium Treponema pallidum

Possible effects of untreated syphillis

• Development of tumors (gummas) on skin, bones, liver

• Hearing loss

• Decreased vision/blindness

• Dementia

• Aneurysms (aorta and other blood vessels)

• Heart valve damage

• Stroke

• Congenital syphilis

Who were the subjects of the Tuskegee Syphilis Study?

Black men were recruited since there were free medical exams, free meals, and burial insurance

Penicillin

the standard and effective treatment for syphilis in 1947, but the subjects were not given it because the focus of the study was to see the effects of untreated syphilis. Subjects were also not told they had syphilis.

Whistleblower Peter Buxtun

• Overheard the Tuskegee Syphilis Study and thought it was unethical

• His family fled before Germany took over, so it made him think about the unethical studies carried out during the Holocaust

• Leaked this information to reporter Jean Heller and she published it to New York Times, ending the study in 1972

National Research Act (1974)

• enacted after the end of the Tuskegee Syphilis Study

• Created the National Commission for the

  Protection of Human Subjects of Biomedical and Behavioral Research

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research wrote the…

Belmont Report (1979), which identified basic ethical principles and developed guideline to assure research is conducted according to those principles

What happened after the end of Tuskegee Syphilis Study?

There was a $10 million class-action lawsuit on behalf of participants and medical benefits were provided to participants and their family. Herman Shaw was one of the survivors who received these benefits. The U.S. government (William J. Clinton) issued an official apology in 1997.

The Hygiene Hypothesis

Increased cleanliness and reduced family size have led to a decrease in early childhood infections, which has contributed to a rise in asthma and allergic diseases. (In other words, being too clean has exposed us to childhood diseases later on, but it is not 100% right)

Helicobacter pylori

• lives in our inner stomach and secretes mucus to protect stomach cells from stomach acid

• produces a lot of urease, an enzyme that breaks down urea, turns into carbon dioxide & ammonia, and reduces the mucus layer to increase the pH (less stomach acid as a result)

The bad thing about helicobacter pylori is that…

it may cause inflammation of epithelial cells (gastritis) —> may evolve into ulcers and stomach cancer

Discovery of Helicobacter Pylori (1984)

• Robin Warren, a pathologist, looked at a stomach biopsy of ulcers and found bacteria

• Barry Marshall, an intern, drank a beaker full of H. Pylori bacteria, developed gastritis, performed Koch’s postulates on himself, but was cured with antibiotics

What led to a decline in infection rate of Helicobacter Pylori?

• Sanitation infrastructure & antibiotics

• Reduced incidence of ulcers and stomach cancer

• HOWEVER, the absence of this bacteria may increase in acid reflux (GERD) and esophageal cancer since it regulates acidity

The Hygiene / ‘Old Friends’ hypothesis

• A lack of early childhood and life-long exposure to certain infectious agents, symbiotic microorganisms, and parasites increases susceptibility to allergic and autoimmune diseases by suppressing natural development and regulation of the immune system

• modification of the hypothesis

Ways to improve immune system for modern living (decrease diversity in microbiota)

• Increased urbanization (decreased exposure to rural/natural environments)

• Decrease in exposure to animals

• Increase in Caesarean sections

• Reduced breastfeeding

• Widespread antibiotic use

• Smaller family size

Single gene disorders

Sickle cell disease, cystic fibrosis, phenylketonuria

Heterozygote advantage

Describes the case in which the heterozygote genotype has a higher relative fitness than either the homozygote dominant or homozygote recessive genotype.

Sickle-cell disorder

• Blood disorder caused by a mutation in the β-globin gene (HBB) —> alteration in amino acid

• Mutation has a strong effect when oxygen levels are low —> mutated β-globin

  chains cause hemoglobin S to polymerize, forming long strands that result in sickle shaped RBCs

Sickle Cell Crisis (Vaso-occlusive (pain) Crisis (VOC))

• Sickle-shaped RBCs obstruct capillaries and restrict blood flow to organs/body parts

• Severe pain, swelling, tissue damage/death

Sickle Cell Crisis (Splenic Sequestration Crisis)

• Trapping of sickle-shaped RBCs in spleen

• Painful enlargement of spleen; severe anemia, hypovolemic shock

Sickle Cell Crisis (Aplastic Crisis)

• Triggered by parvovirus B19 which temporarily prevents RBC production

• Severe anemia, fatigue

Sickle Cell Crisis (Acute Chest Syndrome (ACS))

• Blockage of pulmonary capillaries by sickled RBCs

• Hypoxia leads to increased RBC sickling; a vicious cycle

• Respiratory failure

Polymath

person with a wide range of knowledge across many different subjects; integrate diverse knowledge to solve complex problems

Linus Pauling (1901-1994)

• One of four people to receive two Nobel prizes: 1954 Chemistry (chemical bonds) and 1962 Peace (anti-nuclear activism)

• The only person with two unshared Nobel prizes

• Did not discover the sickle cell disease, but discovered that it was caused by a change in protein

Sickle-cell disease is a…

• autosomal recessive disorder (genetic trait can be passed down to offspring)

• two mutated copies would cause this disease, but one mutated copy provides heterozygous advantage —> protection against malaria

• less oxygen in red blood cell means lower infection levels of malaria

Cystic Fibrosis

• One of the most common life-shortening inherited diseases in the US

• Caused by a mutation in the CFTR gene —> Leads to an overproduction of thick mucus which will clog airways

• Having only one mutated copy protects us against cholera

• Vibrio cholerae is a cholera toxin that activates CTFR but…

  • Less diarrhea since the cystic fibrosis channel is being blocked (which normally allows positively charged sodium ions to flow)

Phenylketonuria (PKU)

• Deficiency in the liver enzyme phenylalanine hydroxylase (PAH)

• Blocks transport of other large neutral amino acids to the brain by saturating LNAAT (amino acid transporter)

• Excessive phenylalanine in blood decrease the levels of other LNAAs, leading to intellectual disability if untreated

What is the heterozygote advantage for PKU?

Ochratoxin A, produced by fungi in stored grains and foods, contains phenylalanine as its structure and causes miscarriage. Raised blood phenylalanine concentration reduces this toxicity, so female carriers of this disorder are protected and have better reproductive success.

Eradication

Permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts; intervention measures are no longer needed. (permanent and worldwide!)

Elimination

Reduction to zero of the incidence of infection caused by a specific agent in a defined geographical area as a result of deliberate efforts; continued measures to prevent re-establishment of transmission are required. (in other words, not permanent removal & not worldwide)

Non-Human Reservoir

• it is where a pathogen naturally lives, grows, and multiplies before infecting humans

• Example: cholera

Vector

• Organisms that transmit the pathogen from one host (or reservoir) to another.

• Example: malaria —> spreads from infectious host to healthy individual

Smallpox

• an eradicated, acute contagious viral disease caused by the Variola virus

• it is only contagious when symptoms start to show up

• Papules - solid red bumps

• Vesicles - red bumps with fluid

• Pustules - red bumps with pus

Edward Jenner

• came up with the first vaccine for smallpox —> inoculated an individual with cowpox virus material

• “father of immunology”

Variolation

• infecting healthy individuals with pustules of smallpox from cowpox through scratching and inoculating with pus

• cowpox is similar to mild smallpox

vaccination

comes from the latin word “vacca,” which means cow

The first vaccine of smallpox

• first tested on James Phillips, 8-year-old son of Jenner’s gardener

• he developed slight fevers, but not severe after the vaccination (injecting fluid from cowpox lesions)

Smallpox eradication

• current vaccine is not based on cowpox, but based on vaccinia virus

• routine smallpox vaccination stopped in 1972

• Ring vaccination strategy - isolate infected people and vaccinate healthy people

• Post-exposure prophylaxis - using preventive medical treatment after exposure to prevent infection

• Intense disease surveillance - identify cases and try to stop the spread where smallpox is occurring

Smallpox post-eradication

• virus is still in storage only in Russia and U.S., kept to produce treatment or better vaccine in the future

• tecovirimat (TPOXX) in 2018 and brincidofovir (TEMBEXA) in 2021 for treatment