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 can’t 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

– Don’t 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 Damon’s blood and inject his antibodies/serum?

• Purified blood product is dangerous, you don’t know what’s still in it• However, it’s 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, can’t 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 person-to-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 Damon’s nice neighborhood); movie didn’t really portray too much of this

• Breakdown of public infrastructure: Garbage disposal, sanitation, sewage treatment (if there’s 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 aren’t 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 wouldn’t model the whole virus, no computer could do that in

that time• Consider making vaccine based just on protein; that didn’t 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 he’d given away vaccine?

• He could spread it to others (as someone who’s highly mobile, that’s 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

don’t 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 Alderson’s name on it • Respiratory virus: chef was stuffing something into slaughtered pig’s

mouth, wiped hands on apron, went out to meet Gwyneth Paltrow (index patient); we don’t know if chef died