(EXAM 3) VBS 2032: Epidemiology & Public Health
indirect transmission modes - examples of each one - what are different types of vectors?
- airborne: particles have been airborne for a while, are smaller, drier, can travel longer distances - fomites: inanimate objects but can harbor an infectious agent + transmit it when you touch it; NOT ALIVE - food/water (contamination + ingest) - vectors: ALIVE; *nonhuman animals = biological vector (part of pathogen's life cycle occurs in the vector). Ex: mosquitoes carry the malaria parasite bc parasite has to go through part of life cycle inside mosquito *mechanical vector: just carries organisms from one place to another... ex: houseflies, cockroaches, fly walking on surface of agar
application of epidemiological terms to cholera in haiti
- before 2010 earthquake, cholera was NOT endemic in Haiti (no known cases) - after earthquake, ppl started getting cholera! • UN troops came in and unwittingly brought in Cholera from endemic countries (asymptomatic carriers) → shed it through bathrooms, not adequate sanitation • rains → privies overflowed, cholera spread into rivers + infected ppl - vaccinating a portion of the population led to a lower incidence of disease through herd immunity
What implications does this research have for current infectious disease epidemiology?
- bubonic plague (Yersinia pestis) still exists in wild populations of rodents, still causes isolated incidents of plague (not common occurance but hasn't been eliminated) - take home message: sometimes an organism can go from being mildly virulent to highly virulent with just a few genetic changes (part of study of emerging infectious disease- what kind of organisms are in animal reservoir and how likely is it that they could infect humans?
Steps in the pathogenesis of infectious disease:
- entry portal - - - the following steps are facilitated by virulence factors - Attachment: microbes have to attach through either receptors on your cells or adhesins on microbe side - Multiplication - Invasion or spread to other parts of the body *microbes that have capability of invading/spreading will cause more serious disease - Evasion of host defenses (innate, adaptive immunity) - Damage to host tissues: either caused by microbe itself (toxins) or by body's own inflammatory response (neutrophils, phagocytes, ROS)
How to flatten the curve:
- restrictions on movement can influence R0 which can influence the shape of the epidemic curve - If R0 is reduced to less than 1, epidemic will stop - with vulnerable populations, once restrictions are lifted, transmission will begin again - goal = decrease # of infections at any one time so healthcare system can handle very ill patients
what happened in the case of legionnaires disease in NYC in 1976?
- when this organism was discovered: causing a type of pneumonia during bicentennial in 76 when lots of older men would've been smokers were at a philly convention, most of them were staying in the same hotel → came down with deadly serious form of pneumonia - CDC brought in, difficult to tell how disease was transmitted bc legionnaires is NOT transmitted from person to person - reservoir was water used in hotel's cooling system (legionella lives in bodies of water) → going into rooms through AC system, ppl breathed it in and became ill (were also predisposed to getting very ill bc of age/immune status) - still a problem today: NYC found 3 hotels in Bronx where it was present in cooling towers
how did researchers set up the study about the virulence/evolution of Y. pestis & what did they predict?
1. Ancestral strain Y Pestis, Pestoides F → limited infection - very early variant of Yersinia pestis - predicted it would probably cause mild disease if infected into mice 2. Ancestral stain Y pestis + Virulence gene pla → pneumonic infection - Yersinia evolved, was found to contain a plasmid (PCP1) → pla gene - hypothesized when organism had additional gene, pla would allow bacterium to cause a more serious disease 3. Ancestral strain Y pestis + MUTATED virulence gene Plal1529T → Disseminated infection - single point mutation (Plal1529T) → means single base substitution led to substitution of amino acid T for I (tryptophan for isoluceine
why doesn't everyone get vaccinated?
1. Compliance: access to healthcare, willing to come in to be vaccinated 2. Ppl CAN'T be vaccinated bc of immune status (ex: immunocompromised person can't get live attenuated vaccine) - depend on herd immunity to protect other ppl
chain of infection steps
1. Infectious Agent 2. Reservoir 3. Portal of Exit 4. Mode of Transmission 5. Portal of Entry 6. Susceptible Host
what were the results of the study on Y. pestis virulence/evolution?
1. Injected ancestral strain into mice → limited infection - bacteria could colonize lungs only to limited extent 2. Ancestral strain and put in virulence gene pla → bacterium could cause pnemonic plague - infected lungs + grew to high density in lungs to the point where it could likely be spread from person-person or mouse-mouse 3. Took pla gene with single mutation (Plal1529T) and infected mice with that → pneumonic plague was more like bubonic plague and could now cause a disseminated infection - bacteria could leave lungs and invade body
4 phases of infectious disease:
1. incubation period 2. prodromal period 3. period of illness 4. convalescent period *you are infectious as far back as incubation period or prodermal period, and when you're symptomatic, as you're getting well, or even after full recovery!!! Depends on disease **can also be exposed to disease → incubation period, divides. Can feel some symptoms (tired, something isn't right), and disease might stop at that point d/t combination of their genetics, host immune system
bubonic plague overview
Combination of... 1. survival in fleas (and rodents) 2. Ability to spread throughout the body → death of millions around the world
koch's postulates overview + steps
Est by Robert Koch in late 1800s → how do we know what agent causes disease? - Koch + Pasteur = germ theory; disease caused by microorganisms Steps: 1. Survey population (humans, mice) → when you have evidence of disease, you should be able to isolate an organism from diseased patient - every case of disease would yield the bacteria of interest, wouldn't typically be found in healthy subject 2. Grow that organism in pure culture 3. Organism has to cause the disease when it's inoculated into a healthy experimental host 4. From those diseased hosts, you'd have to isolate the same organism *not all organisms can be studied using the complete Koch's postulates!!
what did authors want to study about the evolution of Y. pestis & its virulence?
Follow-up: 2nd paper in Smithsonian magazine, describes a molecular koch's experiment (Lathem & Collegues) → compared original strains (progenitor to Yersinia, which was Yersinia pseudotuberculosis → causes mild GI disease, doesn't infect lungs) - made a tree that led from ancestral strain (Yersinia pseudotuberculosis) to 2 strains that are in existence today: could see based on DNA sequences changes that had taken place, drew line between ancestral strains/modern strains - wanted to know if they infected mice with early development strains, what would happen? --> example of molecular Koch's postulates where authors were testing a single virulence factor + single genetic variant of that factor to show that the evolution of Yersinia pestis grew to become more and more virulent/cause more serious disease over time
asymptomatic/subclinical
Microbe has succeeded entry and started to replicate, but person isn't showing classic signs of disease
latent infections
Pathogen is not eliminated from the body, but is not actively replicating; may become activated and cause disease. Infection is not spread. • Herpes simplex virus 1 and 2 (mouth, lip, and genital blisters) → can infect host, cause disease, then DNA of herpes virus is integrated into host genome, where it can stay for years but is not actively replicating • Varicella zoster (Chickenpox) → get it, latent stage/incorporated into host genome → can either never spread it or you get shingles later on in life • Mycobacterium tuberculosis (tuberculosis)
Why does R matter? - how does it relate to herd immunity?
R0 is used to calculate the % of population that needs to be immunized in order to achieve herd immunity and stop transmission • measles: R0 =12-18; 93-95% need to be vaccinated to achieve herd immunity • polio: R0 = 5-7; herd immunity = 80-85% • seasonal influenza: R0 = 1-2; might lower % of herd immunity even further, but bc virus has a high mutation rate, the flu vaccine is not as effective as either the vaccines for measles or polio in general: higher R0 = higher herd immunity threshold
herd immunity
The resistance of a group to an attack by a disease to which a large proportion of the members of the group are immune - vaccination: achieve this so enough ppl are vaccinated to protect others who aren't - transmitting case (sick person) → susceptible → they become sick → transmit to others, disease continues to spread quickly - herd immunity: someone who's sick exposes someone who's immune → person who's immune can't spread it to someone else who's susceptible
susceptible host
a person likely to get an infection or disease, usually because body defenses are weak, last step in chain of infection
portal of entry
a way for the causative agent to enter a new reservoir or host **INTERRUPT: administer vaccine. Even if organism is out + being transmitted, we can protect ppl beforehand
how do you interrupt the chain of infection at the transmission stage?
antiseptics, disinfectants to get rid of it, practice good handwashing
portal of exit
any body opening on an infected person that allows pathogens to leave **INTERRUPT: flu: mouth, sneezing + coughing (stay home, cover cough/sneeze to interrupt) | bacterial infection: treat w abx, isolation precautions
microbial infection
bacterium multiples in body ex: staph aureus; skin infection - commensal/indigenous microbiota (25% of us have staph aureus in nasal passages, don't get sick) transplanted to wound → bacteria can multiply, body defenses removed after skin barrier → disease is a result of ORGANISM itself multiplying
R is NOT a ________________ constant for a pathogen !!! → different in each ______________ where an epidemic is occurring
biological; location
Factors that Influence R:
complex mathematical models take into account the following when R is calculated: • how long is an infected person contagious? (days-weeks-months) • how likely is transmission when ppl come into contact? - how stable is pathogen once it's shed from body, what is the infectious dose? • what is the rate of contact? - human behavior, can easily change compared to the other factors - how many ppl does the average person contact in a day? - dec # of contacts decreases R0 value Also, epi triad. R0 can be different in diverse parts of the world: • environment, some areas have limited access to sanitations, rural vs crowded living factors • host factors: some communities have a high percentage of smokers/more elderly ppl
convalescent period
(movement back to non-diseased state best case scenario); disability or death
what was found in the article about the Y. pestis that caused the bubonic plague?
evidence in bronze age remains of humans → organism that cause bubonic plague was present. Surprising bc we didn't think organism caused disease that far back - authors wanted to find out how organism that was present in teeth of bronze age victims was different from the bacterium is today - sequenced DNA of 2 srtains, compared sequence - found: a major difference between bronze age bacteria + modern day Yersinia pestis (causes plaque) → in bronze age, bacteria lacked a particular disease we know is important for transmission of bacteirum through flea bites, which was YMT gene - ppl in bronze age were likely to have gotten ill from Yersinia pestis, but it probably didn't spread as rapidly as it did in the middle ages bc the bacterium didn't have the gene that would allow it to live in the flea (fleas carry bacteria + infect rats, ppl lived in big city → fleas/rats could spread more quickly than if spread was just person to person interaction)
epidemiological triad
factors influencing disease transmission. interaction between - agent - host - environment
Molecular Koch's Postulates
genetic approach to this problem, something that was possible bc of molecular bio/DNA sequencing → HOW an organism causes a particular disease; what virulence factors are required for a disease, how does disease change when a particular virulence factor is present/absent
effective reproductive number/R
how many cases an infected person will cause IN A POPULATION WITH SOME IMMUNITY - can measure for SARS-CoV-2 once ppl recover - naturally/artifically acquired immunity
basic reproductive number/R0
how many cases an infected person will cause IN A SUSCEPTIBLE POPULATION (where everyone is susceptible) - for SARS-CoV-2 estimate in 2020 was between 1.5-3.5 - different in each location of an outbreak, why?
endemic
infectious agent/disease constantly present in a population - can be present in low level, is always there Ex: common cold is endemic in MN; but malaria is not endemic in MN (used to be in US before concerted effort to eradicate it w draining swamps, mosquito control)
incubation period
interval between initial infection and first signs and symptoms • length is specific to organism. Some have long (divide slowly in host), others have short • influenced by host too
incidence
number of NEW cases in a given time (year) in a given population (usually expressed per 100,000 ppl) Ex: from MDH, there were 375 cases/100,000 ppl in MN in 2014 - ex: incidence of pneumococcal disease caused by strep pneumoniae → normalized per 100,000 ppl. Standardization is important to control small pops + large populations, important bc you're always looking at same base - graph shows alot of things: in any year from 1996-2004, ppl most likely to get sick = <2 yrs, >65 years & incidence has been more or less the same for diff years → disease is endemic, tends to occur at the same rate
R0
reproduction number, can be basic (R0) or effective (R) - how many susceptible ppl a sick person is likely to infect; exponential increase
symptomatic/clinical
showing signs of disease
carrier
someone who's asymptomatic; has pathogen that's replicating/still shedding pathogens/making other ppl sick *contrasts with latent infection Ex: typhoid mary - instead of body ridding salmonella typhi, she had an infection that continued in gallbladder. Wasn't sick but organism continued to proliferate → eliminated via bowels → didn't have good hand hygiene and prepared food → families she worked for got typhoid fever
epidemiology
study of distribution + causes of disease in populations
period of illness
symptomatic • symptoms of disease; characteristic
microbial intoxication
toxin is ingested - ex: various dairy products can contain small amounts of staph aureus, can inoculate food w staph aureus from hands. Certain strains will produce toxins → food poisoning if food is left out for too long *what makes you sick is the TOXIN produced, not the microbe itself! - toxin can be heat resistant (can get sick even without the presence of live bacteria)
application of epidemiological terms to bubonic plague
• Endemic in the U.S. and many parts of the world. 1-17 cases/year in U.S. → incidence is <0.05/100,000 people • Reservoir: rodents • Transmission: - Indirect by flea bite (biological vector) - fluid from infected animal, or respiratory droplets from infected cats. - Direct from respiratory droplets from infected humans. • Mortality: 11% (if treated with antibiotics) • Prevention: rodent surveillance in endemic areas; avoid contact with fleas, rodents or infected animals.
what factors affect disease transmission regarding the agent?
• Infectious Dose required to transmit agent • Virulence • Incubation Period • Antigenic stability • Survival
epidemiology summary
• Koch's postulates: series of experiments identify the organism causing disease • Molecular Koch's postulates: test potential virulence genes • Studying the pattern of disease transmission can also help find the cause of disease. *Limits of experimentation include lack of animal model etc.
what factors affect disease transmission regarding the environment?
• Weather and season • Housing • Geography • Occupational setting • Air quality • Food • Population density Ex: cholera in Haiti → haiti has rainy szn, most of country doesn't have good sanitation, latrines can overflow into rivers → ppl
what factors affect disease transmission regarding the host?
• age, sex - ex: legionnaires for predisposed pop, college dorms/sleep, bacterial meningitis • genetic background • immunization status • Behaviour (sleep, stress, smoking) • Nutritional status • Socioeconomic status • Culture
reservoir of infectious agents - what are some commons of reservoirs? - examples of each one
• infected humans (smallpox, common cold, measles → organisms can only infect humans) - good chance that measles (like smallpox) can be eradicated bc if everyone/large proportion of ppl (>90% vaccinated) → measles won't have a host - hard w common cold bc of variety of viruses that cause • animals (rabies, plague, Lyme disease) - rabies lives in wild pops (raccoons, etc.) →difficult to vaccinate these pops, but can protect ourselves by vaccinating our pets in case that they come in contact with these wild animals • environment (legionnaires' disease/legionella pneumophilia) - *organism needs to leave reservoir and go to next susceptible host to start chain of infection
prodromal period
• not seen in all types of infectious disease • period you feel "off:" sick, tired by no clinical signs of disease yet
transmission - what are some types of transmission? examples of each one?
• vertical: passed from mother to infant, typically occurs bc infectious agent can cross placenta OR if organism is transmitted to baby as its going through birth canal - HIV • horizontal: person to person - cold • direct: <1 meter; don't actually have to be touching person but you're close enough proximity to them - sneeze/cough (droplets can go in the air+ breathe them in), handshake, sexual contact • indirect: more on this below...
→ What are some examples of when Koch's postulates could not be satisfied? - when would we not be able to go through all 4 steps to demonstrate a single organism causes disease?
• when organism cannot be cultured (only 1% of all orgs can be grown in lab culture!) - ex: obligate intracellular pathogen; ricketsia can only grow inside host cells, hard to culture • no animal host - sometimes mice/other animals aren't susceptible to disease, hard to take purified organism to make another organism sick • when an infection is caused by 1+ organisms - can grow something in pure culture but would be missing other orgs that act in concert to cause disease • muddy cases! - diseased subjects should carry organism; healthy subject should not → MUDDY in lots of cases bc healthy subjects CAN carry some organisms and not the ill
