DISEASE E&E (History and Causation) Flashcards
Plagues in medieval Europe:
-life expectancy then was 33 years
-many babies, children and teenagers died from infectious diseases
-causes were unknown and people were mostly helpless against disease
-many believed that plagues were punishment by God
Common diseases in medieval Europe:
-dysentery
-malaria
-diphtheria
-flu
-typhoid
-smallpox
-leprosy
-bubonic plague
Edward Jenner:
-English doctor and scientist
-developed the smallpox vaccine (the world’s first vaccine)
-father of Immunology
Edward Jenner’s work:
-“saved more lives than the work of any other human”
Smallpox
-two variants (variola major and minor)
-characteristic fluid-filled blisters
-transmission between people via contaminated objects
-mortality rate of 30% in infected individuals
-killed hundreds of millions over the centuries
-eradicated in 1980 by WHO via vaccination
Smallpox in Whistlebury:
-Jenner observed that milkmaids were less likely to acquire smallpox
-key observation that the prevalence differed among people with different professions
>lead to development of a smallpox vaccine
Cowpox
-caused by cowpox virus
-causes lesions on udders of cows
-in humans, infection causes localized pustular lesions on the hands
-not dangerous and eventually cleared by the immune system
*exposure causes cross-protection against smallpox
James Phipps and Edward Jenner
-test whether exposure to cowpox against smallpox
-Jenner exposed 8year old boy , James to cowpox
-6 weeks later, he exposed him to smallpox (had no effect)
-inoculated him more than 20x
*unethical to deliberately expose humans to a deadly disease
What was the major obstacle to the scientific understanding of infectious diseases in the 19th century?
-science hadn’t discovered micro-organisms
-causative agent for infectious disease was unknown (pathogen corner had not been discovered)
-miasma theory was the dominant idea
-development of germ theory
Development of germ theory:
-would revolutionize medicine and public health
Miasma theory of infectious disease:
-was the predominant theory of disease transmission
-“bad air” from rotting organic matter
-diseases by environmental factors (water, foul air, poor hygienic conditions)
-no transmission between individuals (no microscopic disease agent)
-disease prevention: avoid locations with poisonous vapours
-replaced by germ theory at end of 19th century
Germ theory of infectious disease:
-many scientists contributed to it
>major contributors were Louis Pasteur and Robert Koch
Louis Pasteur:
-French biology, microbiologist and chemist
*pasteurization
Robert Koch:
-German physician and microbiologist
*Koch postulates
Pasteurization of milk:
-growth of microorganisms was responsible for spoiling beverages such as beer, wine, and milk
>lead to economic losses
-heated liquids (60-100 C) and killed most bacteria and fungi (*pasteurization)
Pasteurization prevented:
-prevent wine, beer and milk from spoiling
*showed that “diseases” of beverages were caused by micro-organisms
*suggested that human disease could also be caused by micro-organisms
Spontaneous generation:
-air can spontaneously cause genesis of life in liquids
Pasteur disproved spontaneous generation:
-used experiments with broth and heat
-boiled broth with open neck seeded by micro-organisms=spoiled
-broiled broth with swan neck=did not spoil despite being in contact with air
*micro-organisms came from outside rather than SG in the broth
Micro-organisms killed by heat:
-critical for the development of medicine and public health
*have an agency to kill micro-organisms
Robert Koch: characterized important bacterial pathogens
-Bacillus antracis: causes anthrax
-vibrio cholerae: causes cholera
-myobacterium tuberculosis: causes tuberculosis
Nobel prize: Robert Koch:
-physiology and medicine
-work on tuberculosis
*showed the importance of spores for bacterial survival in the environment
Bacillus anthracis: agent of anthrax disease
-formation of spores that would remain dormant under specific conditions
-under optimal conditions, the spores were activated and caused disease (ex. eaten or from soil)
-multiplication of bacilli and sporulation
Causative agent of anthrax:
-dry-fixed bacterial cultures onto glass slides
-used dyes to stain the cultures
-observed them through a microscope
*first to link a specific microorganism with a specific disease
Koch’s postulates:
- Microorganism must be found in abundance in all individuals suffering from the disease, but not in healthy individual’s
- Microorganism must be isolated from a diseased individual and grown in pure culture
- Cultured microorganism should cause disease when introduced into a healthy individual
- Microorganism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent
Exceptions to Koch’s postulates:
-not all infected individual’s show disease (asymptomatic carriers)
-not all pathogens can be cultured (ex. prions, viruses must be co-cultured with host cells)
-not all organisms exposed to an infectious agent will acquire the infection
Discovery of viruses;
-germ theory was centered on bacteria, viruses too small for the light microscope
-research on TMB led to discovery of viruses
>naïve plants exposed to infected material=infected with TMD
>material passed through filter still caused disease: small bacteria or toxin
>dilution experiment: infectious agent could replicate and was not a toxin
*’virus’ to describe this new type of infectious disease
TMD and TMV
-tobacco mosaic disease
-tobacco mosaic virus
Electron microscope (EM):
-invented in 1931
Viruses and the electron microscope:
-demonstration that TMV was made of protein and nucleic acid (later shown to be RNA)
-protein crystallography to show that TMV was a particle
-first EM image of TMV made in 1939
-invention of EM was critical for virology
1918 influenza pandemic:
-caused by H1N1 influenza A virus
-first documented case was March 1918 in Kansas
-500 million people infected in 4 successive waves
-estimate of 17-50million people died
-cause remained unknow until 1930s
Richard Pfeiffer:
-German physician and bacteriologist (studied under Robert Koch)
-isolated Haemophilus influenza from influenza patients
>most believed H. influenza caused influenza
-many flu patients didn’t have H. influenza (BLAMED poor culture skills)
-antisera and vaccines against H. influence did NOT help flu patients
*his stature obstructed progress
Richard Shope: influenza in pigs
-influenza like disease in pigs in Iowa (1918 and 1929)
-swine influenza=severe pneumonia
-infected pigs contained Haemophilus influenza suis (HIS) and filterable agent
HIS:
-caused no disease
Filtrable agent:
-caused weak symptoms
HIS + filtrable agent:
-reproduced severe pneumonia in pigs
-HIS is commensal in healthy pigs
*difficult to demonstrate causality if an infection disease is caused by combination of pathogens
>viral pathogen knocks out immune system so secondary bacteria can do opportunistic infection
Virus causes human influenza:
-sample pharyngeal secretions from human influenza patients
-used ferrets as animal model
-filterable virus form human produced influenza-like disease in ferrets
-developed antibody response that protected them from re-infection
-researcher accidently was exposed to sneezing ferret and developed the flu
Lessons learned from 1918 influenza pandemic and Koch’s postulates:
-influenza virus caused secondary infection in H. influenza in human patients
-Pfeiffer incorrectly identified H. influenza as the cause
-important to communicate between medical doctors and veterinarians
-difficult to satisfy Koch’s postulates disease with multiple infectious agents
-human-adapted pathogens may not establish infection in animals models
Viruses and Koch postulates:
-did not meet Koch’s postulates
-Thomas Rivers adapted them
-“blind adherence of them may act as a hinderance instead of an aid”
Viruses and culture:
-can be cell cultured but not in lifeless media
Disease:
-can have multiple etiological agents
Ex. virus and bacterium
Infected animals:
-develop antibody responses to pathogens
>include antibody responses as evidence for a causal relationship
Incubation period:
-interval between exposure and appearance of disease
-some have long incubation periods (years)
-determining causation is more difficult for long incubation periods
BSE:
-pathogen: prion
-incubation 4-6 years in cattle, 12 years in humans
Cancer:
-pathogen: oncoviruses
-incubation is years
Oncoviruses:
-are viruses that cause cancer in their host
-integrate their genome into host genome
-can cause cancer by 2 mechanisms
Oncoviruses examples:
> papilloma viruses
hepatitis viruses
herpesviruses
retroviruses
MMTV
FeLV
2 mechanisms for oncoviruses:
- Viral genome contains cancer promoting oncogenes
- Integration of viral genome into host genome disrupts cancer-suppressing oncogens
Johne’s disease:
-pathogen: MAP
-incubation 2-5years in cattle
AIDS:
-pathogen: HIV
-incubation 10 years in humans (in absence of treatment)
ASLV and RSV: (oncoviruses
-causes sarcomas and lymphomas in chickens
>injection with tumor filtrate caused cancer in healthy chickens
*idea that infectious agents cause cancer was “utter nonsense”
Lessons learned form oncoviruses:
-incubation period for some diseases can take years
-infection with oncovirus can result in cancer years later
-infectious agents can cause unexpected diseases
-many types of cancers have a viral organ
-dogmatic thinking impedes progress
