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Contagion!

What characteristics of a pathogen and the human


population could contribute to a sudden disastrous
epidemic?
What are the options for control at various stages of an
epidemic with and without anti-infectives or vaccines?
How can an epidemic damage the structure of our society?
What is the role of the medical community, and physicians
in particular, in responding to a severe epidemic?
How would you respond as a physician if a similar disaster
hit your town?

What characteristics of a pathogen and the human population


could contribute to a sudden disastrous epidemic?
Virus can persist for long periods of time outside of host
Virus can mutate quickly
If antigens keep changing, then our immune system cant keep up and eliminate the pathogen
Theoretically, Matt Damon could have lost his immunity(?)
Selective pressure selects out viruses with mutated cell? binding sites (what about antigen binding sites? )
Mutation can also select for viruses that have mutated binding sites for a drug

How would a rapid mutation rate be beneficial for a virus?


Second exposure, what would protect you, if at all?
Circulating antibodies in system (e.g., maternal antibodies give neonates 6 months of immunity); memory
B cell antibody production will need to be called from memory to augment response
On second exposure, you will be protected IF you have enough circulating antibodies
Antibodies will enable: neutralization (Binding to cell-attachment proteins), opsonization (pulls in innate response),
complement activation via classical pathway (helps only with ENVELOPED viruses)
T cell response take too long (no pre-formed effector mediators) to respond to pathogen that kills within 48 hours
(remember, DTH); cytokines are inflammatory, too much can result in collateral damage /friendly fire

Infectious/onset of transmissibility while still exhibiting mild/few symptoms => can spread
more easily b/c victim goes to work/school
Dont want to kill too quickly (that could limit spread of pathogen)

Pathogen that creates lots of respiratory aerosols can facilitate its spread (even breathing can
create fine aerosols) (e.g., 1918 influenza)
Epidemics: dense population (Chicago, Tokyo, etc), air travel; Ebola in Freetown, Sierre Leone
(Freetown is densely populated) when it was still confined to villages, ppl just shunned
villages, and disease fizzled out;

Forsythia: as physicians, how to deal


with misinformation on social media?
truth: autism study was done by fraudulent physician
Trust: lack of transparency caused public to distrust CDC
A lot of ppl get info from Facebook, rumors spread => panic
(too many sources of info); it used to be ppl listened to radio
(one central news-source)
If you shut down FB, panic could get worse; might be good to
encourage ppl to socialize digitally (prevents spread of
pathogens)
On the population /public health level, there should be a
Public Information Officer (need chain of command, someone
who gathers all information and acts as spokesperson for
what needs to be done and when)
EIS = Epidemic Intelligence Service; Homeland Security, CDC; CIA
probably involved too in Contagion

Why not just purify Matt Damons


blood and inject his antibodies/serum?

Purified blood product is dangerous, you dont know whats still


in it
However, its possible: Ebola serum was created; however, we
also know that Ebola can recur (one English women developed
meningitis after recovering from Ebola); immune system had it
under control for awhile, but ultlimately lost
It would take a while to try to clone the antibody
ALTERNATIVELY, Matt Damon might just have evaded infection in
the first place, might not have antibodies, but simply avoided
getting infected in the first place (like the delta mutation for
HIV) (maybe he has a variant receptor that resists the virus
binding, cant amplify virus to levels high enough to transmit to
others);
However, he was exposed to high levels of virus (most of his family
died); maybe his innate system is just super strong
Could test for circulating antibodies or virus (viral nucleic acid can be
detected using PCR, fastest method)
If Matt Damon was simply resistant to virus, realistically he would have
killed his daughter

What are the options for control at various stages of an


epidemic with and without anti-infectives or vaccines?
Isolation unit (the gymnasium that Kate Winslet set up)
Put most febrile patients at one end (layers of
quarantine within a quarantine unit)
Was their isolation procedure effective?
Ppl wearing surgical masks
Stop touching your face Dave
Even micro-puncture in skin
Nurses in Texas got Ebola probably b/c tape holding isolation
equipment came into contact with skin

Cancel major events / shut down major places of


gathering (Ebola: community leaders reduced personto-person contact as well as large gatherings)

As physician, how can we help these patients


(if no antiviral drugs or vaccines exist)?

Supportive/nursing care (if lungs


damaged, give oxygen; if like
rotavirus, severe dehydration =>
give hydration)

Public health implications of Contagion:


what started to break down, how did it
snowball? How can an epidemic damage
the structure of our society?
Forsythia, fight for survival resources: ppl rioted at pharmacy
trying to get Forsythia => more contact => pathogen spreads
Breakdown of public order: Ppl will take opportunity and loot in
emergency situations (Hurricane Katrina) (robbers in Matt
Damons nice neighborhood); movie didnt really portray too
much of this
Breakdown of public infrastructure: Garbage disposal,
sanitation, sewage treatment (if theres a sewage backup and
sanitation workers are too fearful to go to worker =>
secondary cholera outbreak)
No unified public health system in US: we have a public health
dept in every state and for each city; difficult to coordinate;
difficult to establish chain of command

What is the role of the medical


community, and physicians in
particular, in responding to a severe
epidemic?
Ebola: excess mortality was 3-4
times higher than normally would
have died from Ebola, b/c healthcare
workers died (many were
overwhelmed and died); if nurses or
doctors arent around, patients die
Redundancy to provide continuity of
care: hospitalists help manage
patient care vs. specialists that come
and go

Steps of developing vaccine?


In movie, researchers tried to grow the pathogen (need to have
enough of it to study the structure of the pathogen, molecular
modeling, to study cell-receptor-binding); needed to guide
devlpmnt of productive [adjuvant?]
Inaccuracy: you wouldnt model the whole virus, no computer could
do that in that time

Consider making vaccine based just on protein; that didnt


work, so made vaccine using live attenuated (suggests vaccine
activates CTL killer T cell response); she injects herself, went to
visit her Dad (Hollywood moment, but some medical
professionals have done that in real life: man who discovered
yellow fever virus was arbovirus, tested hypothesis by putting
cage full of mosquitoes on arm of someone dying of yellow
virus, let himself get 20 bites => he knew there was no
therapy, he died)

Ramifications/ethics of CDC head putting


on vaccine band even though hed given
away vaccine?
He could spread it to others (as
someone whos highly mobile, thats
pretty risky)
He would have known the risk and R
value for the virus, as someone
deeply involved in these discussions

Intramuscular to Nasal Spray: how


did they change the virus?
Normally, you go through new set of
human trials; for each route, establish
dosage, frequency, boosting
HCV in Egypt: advantage of using nasal
delivery is
mucousal IgA protection
No needles (used needles are dangerous if
you dont sterilize needles properly, or train
healthworkers properly, you could end up with
infecting more ppl with some other pathogen)

Origin of Contagion virus


Bat and pig: bat deposited virus on saliva/fruit, pig ate fruit that
fell on ground, pig virus and bat virus meet => reassortment
1918 flu strain was recombinant & reassortment from multiple
species
Starts with bats: largest reservoirs of mammalian viruses in the
world
Some viruses can be damaging to one type of cell and replicate
non-lytically in other cell types (full animal body has immune
system) (virus can behave differently in tissue culture dish
compared to live animal)
Tractor had Aldersons name on it
Respiratory virus: chef was stuffing something into slaughtered
pigs mouth, wiped hands on apron, went out to meet Gwyneth
Paltrow (index patient); we dont know if chef died