Outbreak! Investigation and Response Simulation Module

Can you identify the pathogen and control the outbreak?

The Scenario

A cluster of severe, atypical respiratory infections has been reported at Atrium Health Wake Forest Baptist hospital.

  • Initial PCR panels rule out common seasonal pathogens.
  • Several of the patient reports having visited a local farmer’s market where they purchased a live chicken and other livestock were present.

The Response Team

An incident command center has been activated to coordinate the response.

The response team is responsible for the following:

Picture credit: US CDC

Pathogen Identification and Diagnostics

This group will be responsible for taking the specimens that were collected from the field team and identifying the pathogen that is causing the outbreak.

Objective Identify the pathogen within the time and budget allotted.

You only have 48 hours to identify the agents and a limited budget.

Questions

  • Did you identify the pathogen?
  • What kind of constraints did you operate with?
  • Did all of the specimens test positive? Why or why not?
  • Were specimens testing positive for multiple things?

Image: CDC/ Robert Denty

Diagnostics Available

You only have the specimens that were collected from the initial field team.

Diagnostic Description Cost Time
Culture Bacterial Culture $500 2 hours
PCR Multiplex PCR $2,000 4 hours
EM Electron Microscopy $5,000 8 hours
WGS Metagenomic WGS $15,000 24 hours

Testing Response Team

This group is responsible for designing our testing plan.

Objective: Maximize testing coverage within the budget, minimize false negatives and false positives, and limit the response time to 21 days.

Questions

  • What was the optimum configuration given your budget? How long would it take to deploy?
  • How did the assay choice impact your testing coverage, cost, and time line?
  • What do you think the conseqences of false negative/positives would be in a response?
  • If money were no object, how much would it cost to use all of each type of test?

Image: CDC/ John Saindon

Testing Response Team

You can select any combination of diagnostics to deploy–but you have to have staff to run the tests.

Diagnostic Image Sensitivity Specificity Cost Time
PCR Multiplex PCR 95% 99% $50 ~10 per hour
LAMP LAMP 85% 95% $10 ~21 per hour
RAT RAT 70% 97% $5 ~42 per hour

Medical Countermeasures Team

This team must decide the therapeutics to deploy.

Objective: Minimize the peak hospitalized and total number who become die from infection.

Questions

  • Set the number of vaccine technicians to 0. This note the peak hospitalized and total number who succomb to infection.
  • Note the day of the peak number of infections with and without antivirals
  • What happens to these numbers (peak hospitalizations and number dead) when you add in antivirals? What else happens?
  • If you deploy vaccinations, what happens?
  • Explore the simulator to come up with a reasonable budget request to the mayor
  • What would the price per vaccine need to be if you had 20 technicians to reduce the peak number of infections by 50%?

Medical Countermeasures Team

The vaccine costs $10 per dose, but it takes 14 days to get here from the national strategic stockpile.

  • Vaccination requires technicians to administer the vaccine, which costs $10 per hour.

You have general antivirals that can be given to everyone (at 10,000 people per day),

  • Reduces symptom duration by 50%
  • Can induce selective pressure for resistance

Image: CDC/ National Strategic Stockpile

Animal Field Team

This team will focus on controlling the outbreak among the animal population, representing the Animal Plant Health Inspection Service (APHIS).

Objective: Balance the recommendations from culling (and what size) versus vaccination or some combination of the two approaches to minimize the number of birds culled, minimize the cost, and stop the spread of the pathogen.

Questions

  • What strategies were most sucessful in stopping the outbreak?
  • What was the lowest cost strategy overall?
  • What were some of the challenges with the different control options (vaccination, culling, cull ring size)?
  • What do you wish you could do?

Animal Field Team

Note that broilers can be sold for $5 each.

Vaccination costs $1 per bird, but it takes several days to vaccinate all of the animals on a given farm due to personnel limitations.

The other option is culling in a ring, which will sacrifice healthy birds to prevent onward spread. The USDA will reimburse farmers $3 per every sacrificed bird

  • Represents a net loss for the farmer of $2 per bird and ultimately a cost to the taxpayer of $3 per bird
  • Impacts food prices

Image: APHIS/ USDA

Field Epidemiology Team

This team will be responsible for conducting an epidemiological survey to map potential exposure sites. They will have to balance the cost of the survey with the potential exposure sites you can find.

Objective: Characterize the transmission chain of the pathogen.

Questions

  • What was the most cost-effective strategy for finding exposure sites?
  • What was the least cost-effective strategy?
  • What were some of the challenges with the different survey options?
  • How would we use this information during this outbreak and beyond?

Zoonoses Outbreak Response Always Operates Against Constraints

  • Limited time to response
  • Limited information to go on
  • Limited resources to use
  • Limited budget to spend

Image: WHO

Outbrief

Appendix

Zoonotic Diseases

For our scenario, we might have had the following dynamics:

The Ecology of Spillover

Outbreaks rarely jump directly from a wild reservoir to humans. They often utilize an intermediate amplifying host to acquire the necessary genetic changes to become zoonotic.

  • Reservoir: Avian (Poultry/Wild birds)
  • Intermediate: ? (Requires epidemiological survey)
  • Spillover: Human (Hospitalized patients)
  • Dead-ends: Environmental persistence or pasteurized products.

The Mathematics of Mutation

To reconstruct the chain, we rely on the molecular clock. We will utilize the Jukes-Cantor (JC69) model to estimate genetic distance.

Raw sequence differences underestimate true evolutionary time due to multiple substitutions at the same site.

\[ d = -\frac{3}{4} \ln\left(1 - \frac{4}{3}p\right) \]

Where \(p\) is the proportion of differing sites between two aligned sequences.

Conducting the field survey

  1. Open the interactive HTML simulator.
  2. Conduct an epidemiological survey to map potential exposure sites.
  3. Balance your budget to collect virological samples across locations.
  4. Generate the phylogenetic tree to visualize the transmission chain.
  5. Download the FASTA sequences and calculate your genetic distance matrix.

Goal: Resolve the complete transmission pathway before the budget runs out or the viral trail goes cold.