The Terrible Law: Basic Epidemic Dynamics

Justin Lessler, PhD

Johns Hopkins University
How Do
Epidemics Grow

“If we do not get the disease under by the middle of April, prepare
yourself for a calamity beyond all calculation … Wait, and you will
see the averages, which have been thousands, grow to tens of
thousands, for there is no reason why the same terrible law of
increase which has prevailed hitherto should not prevail
henceforth.”

—Robert Lowe to the British House of Commons, 1866

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 The Terrible Law?

Source: Popular Science Monthly. (1883). Volume 23. Accessed on May 8, 2019, from https://archive.org/details/popularsciencemo23newy/page/n6;
graph accessed on May 9, 2019, from https://www.r2library.com/resource/detail/1449683797/ch0006s0137#goto=ch0006s0137fg0043 3
Objectives

► Introduce basic measures of disease transmissibility

► Define the reproductive number and how it varies over the course of an epidemic

► Explain the dynamic quantities that characterize the natural history of an infectious
disease

► Relate measures of transmissibility and disease progression to epidemic dynamics and

control

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Recommended Readings and Resources

► Links to reading material are available in the Online Library

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Measures of Transmissibility: Attack
Rates

The material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under
rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.
Measures of Transmission

► Attack rates ► Reproductive numbers

► Basic attack rate (AR) ► Basic reproductive number
► Household secondary attack rate (SAR) ► Reproductive number
► Susceptible exposed attack rate (SEAR)

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Raw Attack Rate

► Simple measure of those at risk vs. those

infected

► Takes no account of differences in

exposure, susceptibility, etc.

𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 3
𝐴𝐴𝐴𝐴 = = = 60%
𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 5

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Household Secondary Attack Rate

► Proportion of cases infected in a household due

to household exposure

► Usually calculated assuming a single index case

► A proxy for infectiousness dependent on

exposure

𝐼𝐼 − 1 2
𝑆𝑆𝑆𝑆𝑆𝑆 = = = 50%
𝑁𝑁 − 1 4

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Susceptible ► Proportion of potential infection events that actually occur
Exposed Attack
► Denominator is those at risk for infection on each generation of
Rate transmission

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Key Points

► Attack rates are the most basic measure of transmission and transmissibility

► More precise definitions of the risk set make attack rates more directly capture
transmissibility
► Full population: raw attack rate
► Non-index household members: household secondary attack rate
► Possible infection events: susceptible exposed attack rate

► Not all can be realistically estimated in all circumstances

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Exercise

► Consider a population of 20 people living in 5 equally sized households

► You observe 8 cases spread across 3 households

► Calculate the attack rate

► Calculate the household secondary attack rate

► What assumptions did you need to make to do this?

► What additional information would you need to calculate the susceptible exposed attack
rate?

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Measures of Transmissibility:
Reproductive Numbers

The material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under
rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.
The Basic Reproductive Number

► The number of people infected by a single

infectious individual in a fully susceptible
population

► Commonly denoted 𝑅𝑅0

► A basic measure of disease transmissibility

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The Reproductive Number

► The number of people infected by a single

infectious individual in a population with
immunity

► Commonly denoted 𝑅𝑅

► 𝑅𝑅 is usually equal to 𝑅𝑅0 × % susceptible

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The
Reproductive
Number and
Epidemic
Curves

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The Basic
Reproductive Disease 𝑹𝑹𝟎𝟎
Number of Cholera 2.5–15
Some Diseases Dengue 1.3–6
Influenza 1.5–2
Malaria 1–>1000
Measles 11–18
SARS 1.2–4
Smallpox 3–7

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Key Points

► The basic reproductive number (𝑅𝑅0 ) is a core measure of disease transmissibility

► 𝑅𝑅0 is a function of both disease and context

► In populations with immunity, the number of people a case infects is 𝑅𝑅

► The value of 𝑅𝑅 determines if cases of a disease are rising, declining, or stable

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Exercise

► If the basic reproductive number (𝑅𝑅0 ) for cholera is 3, what is the approximate percent of
the population immune when an epidemic starts declining?

► Think about:
► What is the reproductive number (𝑅𝑅) at different times of the epidemic?
► What is the relationship between 𝑅𝑅 and susceptibility?

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Natural History

The material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under
rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.
Key ► Latent period
Distributions in
► Incubation period
Course of
Infection ► Generation time/serial interval

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The Latent Period

► The latent period is the time from being infected to becoming infectious

► Requires assumptions to measure

► Pathogen shedding
► Timing of infection among contacts
► Modeled processes

► Important for its relation to the incubation period

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The Incubation Period

► The incubation period is the time from being infected to developing symptoms

► Can be measured if we have an estimate of time of exposure and symptom onset

► Exposure time is usually a range

► Tells us when cases are picked up by surveillance

► Active symptom surveillance
► Passive surveillance

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The Generation Time

► The generation time is the time between subsequent generations of infection

► Time from me being infected to infecting others
► Not directly observable

► Approximated by the serial interval, the time between symptom onset on subsequent
generations of infections
► Time between me developing symptoms and the time between the people I infect
developing symptoms

► Along with 𝑅𝑅0 dictates growth of epidemic

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Generation Time and Growth

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The Distribution of Key Periods

► The incubation period, latent period, and

generation time tend to follow long-
tailed distributions

► This means that while most people will

develop symptoms (become infectious,
etc.) in a short time, a few will take much
longer to do so

► Examples of long-tail distributions include

the log-normal and gamma

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Key Points

► The incubation period is the time from infection to symptom onset

► The latent period is the time from infection to becoming infectious

► The generation time is the time between subsequent generations of infection

► Approximated by the serial interval

► The generation time combined with the reproductive number determines how fast
epidemics grow

► All three distributions tend to have long right tails

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Exercise

► Measles has an 𝑅𝑅0 of 12 and a generation time of 12 days

► Influenza has an 𝑅𝑅0 of 2 and a generation time of 4 days

► In an epidemic in a completely naïve population, how many people would be infected

after 24 days?
► Assume there is not enough immunity accumulates in that time to change 𝑅𝑅

► What if 50% of the population were immune at the start of the epidemic?

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Implications for Control

The material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under
rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.
𝑅𝑅0 and Control—1

► When the reproductive number

falls below one, the number of
cases will decrease

► Any control measure that

causes 𝑅𝑅 to be less than one
will ultimately be successful

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𝑅𝑅0 and Control—2

► If 𝑅𝑅 is less than one before an

epidemic starts, the population
is effectively protected from
that disease
► Herd immunity

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The Critical Vaccination Threshold

► Simple algebra gives us a formula for ► 𝑉𝑉 is referred to as the critical vaccination

what proportion of the population you threshold
would need to be successfully vaccinated
to bring 𝑅𝑅 below one: ► For example, if the 𝑅𝑅0 for measles is 11–
19, we need to vaccinate 91–94% of the
1 population to prevent measles outbreaks
𝑉𝑉 = 1 −
𝑅𝑅0
► Similar logic can be used for any
intervention

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Natural History and Control

► The incubation period tells us when cases can be detected by passive/symptom-based

surveillance

► The latent period tells us when they will be infectious

► These values have implications for the success of different intervention strategies
► Quarantine
► Symptom-based control strategies

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Quarantine

► Quarantine is the segregation of people

potentially infected with a disease until we
are confident they are not infected
► Differs from isolation of those already
infected

► Correct length based on incubation period

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Active ► Active monitoring is a less extreme alternative to quarantine
Monitoring
► Used in the US during the 2014–2015 Ebola outbreak

► Depends on latent period being longer than incubation period

Source: Reich et al. (2018). Scientific Reports. Licensed under creative commons
http://creativecommons.org/licenses/by/4.0/ 7
Case-Based Control Measures

► Case-based control measures are any control strategies based on intervening on

symptomatic cases
► Treatment
► Isolation
► Symptom screening at borders

► Effectiveness depends on the percentage of infections caused by symptomatic cases

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Key Points ► If 𝑅𝑅 is brought below 1, an epidemic will die out

► 𝑅𝑅0 tells us the percent of the population we need to

successfully vaccinate to protect the population from
epidemics through herd immunity

► The incubation period can be used to help determine the

length of our quarantine or active monitoring

► The relationship between the incubation period and the latent

period tells us if case-based interventions will work
► If the incubation period is much longer (for example, HIV)
they will be doomed to fail, while if only symptomatic cases
transmit (for example, smallpox) they may be effective

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Exercise

► Consider that the 𝑅𝑅0 for cholera is 3

► Assume symptomatic cases cause 90% of infections

► Assume you can treat symptomatic cases before they can cause any additional cases

► What percentage of symptomatic cases would you have to treat to bring 𝑅𝑅 under 1 and
prevent an outbreak?

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Summary

The material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under
rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.
Summary—1 ► Transmissibility of infectious diseases can be measured in two
ways:
1. Probability of being infected (for example, attack rates)
2. Number of cases caused by infectious individuals (the
reproductive number)

► The basic reproductive number 𝑅𝑅0 tells us transmissibility in a

fully susceptible population
► As susceptibility decreases, so does 𝑅𝑅

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Summary—2 ► Three distributions provide critical information on the natural
history of disease as it relates to transmission and control:
1. Incubation period
2. Latent period
3. Generation time

► The possibility for control and performance of control

measures can be understood in terms of these quantities