DISEASE E&E (History and Causation) Flashcards by Danielle Groenendijk

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

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Common diseases in medieval Europe:

-dysentery
-malaria
-diphtheria
-flu
-typhoid
-smallpox
-leprosy
-bubonic plague

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Edward Jenner:

-English doctor and scientist
-developed the smallpox vaccine (the world’s first vaccine)
-father of Immunology

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Edward Jenner’s work:

-“saved more lives than the work of any other human”

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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

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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

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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

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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

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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

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Development of germ theory:

-would revolutionize medicine and public health

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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

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Germ theory of infectious disease:

-many scientists contributed to it
>major contributors were Louis Pasteur and Robert Koch

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Louis Pasteur:

-French biology, microbiologist and chemist
*pasteurization

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Robert Koch:

-German physician and microbiologist
*Koch postulates

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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)

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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

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Spontaneous generation:

-air can spontaneously cause genesis of life in liquids

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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

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Micro-organisms killed by heat:

-critical for the development of medicine and public health
*have an agency to kill micro-organisms

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Robert Koch: characterized important bacterial pathogens

-Bacillus antracis: causes anthrax
-vibrio cholerae: causes cholera
-myobacterium tuberculosis: causes tuberculosis

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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:

1. Viral genome contains cancer promoting oncogenes 2. 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