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growth spurts
driven by technologic advances: invention of tools, agriculture, industry
plateaus
set by birth/death rates – limiting factors: disease, famine, war, birth control
how is the agricultural revolution associated with disease?
crowding - enhanced disease transmission (respiratory), human/animal manure as fertilizer (water/foodborne disease), poor nutrition from primarily grain crops
origin of influenza a
ducks, pigs, wild birds
origin of measles
cattle
origin of smallpox
camels
origin of tuberculosis
ruminants
origin of mumps
mammals, possibly pigs
origin of rotavirus a
domestic herbivores
origin of diphtheria
domestic herbivores
origin of pertussis
mammals
origin of plague and typhus
rodents
origin of cholera
aquatic organisms
origin of hepatitis b
apes
origin of aids
chimpanzees
origin of yellow fever
african primates
origin of dengue fever
old world primates
emerging infectious diseases
diseases that have increased recently or could increase in the near future
zoonotic
transmission to humans from animal reservoir
why is zoonotic transmission from bats high?
ability to fly, body temperature fluctuations, roosting habits, migration, hibernation
human monoclonal antibodies
isolate antibody-producing cells from convalescent individuals, clone and sequence the antibody genes, prepare synthetic human antibodies
cause of death categories
communicable (infectious and parasitic diseases, maternal, perinatal, and nutritional conditions), noncommunicable (chronic), injuries
years of potential life lost (ypll)
assesses "premature“, "preventable“, and "unnecessary" mortality
crude mortality
treats deaths at all ages equally
major causes of death years 1-9
unintentional injuries, cancer, congenital malformation
major causes of death years 10-24
injuries, suicide, homicide, cancer
major causes of death years 65+
heart disease, cancer, chronic lower respiratory disease
what receives low funding
gun violence and falls
what receives high funding
HIV
disability adjusted life years (daly)
number of productive years lost due to ill-health, disability, or early death
disease
a change from general good health, involving disruption of normal structure or functioning of body
disease causes
inadequate nutrition, genetic abnormalities, structural or functional disorders, trauma
infectious agents
prions, viruses, bacteria, fungi (protozoa)
prions
single protein – too small to represent here
viruses
average about 100 nanometers; have few proteins; must commandeer the machinery of the
cells they invade to reproduce
bacteria
sizes vary, but are at least ten times bigger than viruses; single cell organisms, and can reproduce independently
single-celled parasites
at least ten times larger than bacteria
multicellular parasites
so large they can often be seen with the naked eye; tapeworms can be 20 feet long
eubacteria
bacteria of medical importance
archaebacteria
collection of evolutional distinct organisms; primarily found in extreme terrestrial and aquatic environments
where do antibiotics work?
cell wall and cytoplasm
where do antibodies work?
cell-surface
PAMPS - pathogen-associated molecular patterns
conserved structures on microorganisms, genetically encoded to be recognized by the innate immune system, jump-start the immune response, and can cause symptoms of disease in the absence of living bacteria, including the cell wall structures of bacteria
cell wall (peptidoglycan)
protects from environmental stresses, provides strength, maintains bacterial shape, limits penetration of molecules
medical importance of cell wall
protects from some host defenses, role in adherence to host cells
selective toxicity
unique to bacteria, target for many antibiotics
capsule functions
protection from harsh environment, permeability barrier, surface attachment - including host tissues, mutans attaches to teeth and causes tooth decay), capsules are antigenic – can induce protective antibodies that promote engulfment by phagocytes
capsule pathogenicity (survival in host)
encapsulated = virulent; no capsule = avirulent
what does the capsule protect bacteria from
phagocytosis
flagella
rope-like filaments of coiled flagellin
role of motility in pathogenesis
mediates tissue invasion, traverse cellular/extracellular barriers
chemotaxis
swim through intestinal mucus barrier, access intestinal cells
pili
attachment of environmental surfaces, bacterial sex (conjugation), host cells; transformation (uptake of DNA)
sporulation
bacteria form endospores
endospores
highly resistant, dormant structures—to survive harsh environmental conditions
what are spores resistant to killing by
heat (2+ hours boiling), drying, freezing, pH extremes, deterious chemicals, antibiotics, radiation
sterilization procedures
bleach, autoclaving (exposure to high temperature and pressure)
toxicity steps
1. b-component binds to receptors on the host target cell
2. b-component promotes entry and cellular trafficking of toxic a-component
3. a-component causes a specific alteration in the target cell that leads to the dire consequences
cytolytic toxins
cause cell lysis
cytotoxic toxins
cause metabolic alterations
most deathly agents
tetanus and botulinum toxin
diphtheria toxin
inactivates ribosomes, protein synthesis stops, and cell dies
diphtheria
upper respiratory tract infection, transmitted by droplets, leads to airway obstruction, toxic myocarditis and heart failure, and nerve paralysis
cholera toxin
leads to watery diarrhea
tetanus and botulinum toxins
no vesicle fusion, blocks release of neurotransmitters (botulinum blocks release of acetylcholine)
c. tetani
produces tetanus toxin; characterized by uncontrollable muscle contractions; spastic paralysis
c. botulinum
produces botulinum toxin, characterized by flaccid paralysis
virulence
degree of pathogenicity of a microorganism, or how effectively it can cause disease in a host
vaccines
contain agent that represents disease-causing organism that’s often made from weakened/killed forms of microbe that stimulates immune system to recognize it as a threat and destroy it if it encounters it in the future
active immunization
produced by pathogen
naturally acquired = recovery from infection
artificially acquired = vaccination
passive immunization
produced by antibodies or cell from an immune individual
naturally acquired - maternal transfer of immunoglobulin via milk
artificially acquired - immune globulin
toxoids
chemically or genetically inactivated toxins with immunogenicity retained
attenuated pathogens
live agents that induce a protective immune response without causing disease
adjuvants
substances that enhance immune response, ex. alum, Freund’s adjuvant
humoral immunity
antibodies are produced to clear or inactivate toxins or pathogens circulating outside the
cells in our body; activated by extracellular antigens; effective against many bacteria and toxins, some circulating viruses
cellular immunity
t-cells are produced that recognize and kill infected cells or induce inflammatory responses; immunity induced by antigens produced inside cells; effective against viral infection
killed vaccine pros + cons
pros: low-tech, easy to prepare, cheap
cons: toxicity, short-term immunity
attenuated vaccine pros + cons
pros: sustained stimulus, right immunity
cons: reversion to virulence, harmful to immunocompromised
subunit vaccine pros + cons
pros: low toxicity, no reversion
cons: poorly immunogenic, may need adjuvant, expensive
killed (inactivated) vaccine examples
non-viable pathogens
bacterial: pertussis, cholera, plague, typhoid, anthrax
viral: polio, influenza, hepatitis A, rabies, encephalitis virus
subunit vaccine examples
antigenic components
toxoids: inactivated toxins. ex. diphtheria, tetanus
capsules: often conjugated with proteins to improve immunogenicity, ex. H. influenzae (Type B), N. meningitidis, streptococcus pneumoniae (23 capsule types)
bacterial: pertussis
viral: hepatitis B surface antigen, human papillomaviruses
live-attenuated vaccine examples
bacterial: BCG for tuberculosis, tularemia, typhoid fever
viral: polio, measles, mumps, rubella, chicken pox, adenovirus, yellow fever, smallpox, rotavirus, influenza
RNA vaccines
covid-19
herd immunity
transmission is limited, unvaccinated are protected
efficacy
calculated by comparing the number of cases of disease in the vaccinated population vs. a control group in an exposed population
VAERS - vaccine adverse event reporting system
voluntary reporting system for reporting adverse events after vaccination