A MOOC of the Institut Pasteur

Modeling of Infectious Diseases

 Chapter 2 –Session 2

Intervals of interest in infectious diseases

Pierre-Yves BOËLLE
Professor

Sorbonne Université

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 Natural history : A clinical view

• Incubation : Time from infection to symptoms

From few hours to decades, depending on the disease
• Flu : 12h-36h / Measles : 14 days / HIV: > 7 years
• Clinical/Symptomatic phase : stage with symptoms
From none to lifelong

susceptible incubation clinical cured

time
infection symptoms

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 Distribution of incubation time

• Incubation is of interest because

Exemples of incubation periods
disease can not be diagnosed
• Incubation changes with individuals flu SARS
2
2
2
2

• Most incubation periods of acute

diseases have a skewed distribution measles

Lessler LID 2009

Median < Mean (long periods possible)
Log-normal, gamma

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 Natural history : An epidemiological view

• Latent : infected but not contagious/infectious, typically « E » or « L »

• Infectious : infected and contagious/infectious, typically « I »
• Removed : infected and removed or no infected anymore, « R »
• These stages are not directly observable (begin/end)
Convenient framework to discuss transmission

symptoms

Clinical susceptible incubation symptomatic cured

Epidemiological 1 latent infectious removed time

infection

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 Relation between clinical and epidemiological stages

• Latency and Incubation

Most often, latency is shorter than Incubation

• Flu, COVID-19, most diseases transmitted by respiratory airways
• People who are still incubating may start being contagious
• More difficult to control

Sometimes, latency longer than incubation

• Smallpox, SARS…
• Presumably easier to control

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 Relation with compartmental modeling

• In making compartments in a model, we should capture first the

« epidemiological » view
• Describe first stages with differences in transmission

S E I R

Susceptible Latent Infectious Removed

• Stages with difference in clinical expression can also be of interest to output

specific data Infectious asymptomatic

IA

S E R

IS
Infectious symptomatic

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 Intervals between successive cases

• Generation interval : The interval between a primary case infection

and infection of a secondary case
Determines the speed of epidemic spread

Directly transmitted Vector-borne

infection infection
Primary Case Primary Case

vector

Secondary Case
Secondary Case

GI GI

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 Relating intervals to natural history

• Minimum and maximum generation intervals

Shortest : latency Longest : latency + infectious

Latency period Latency + Infectious period

In a single primary case : secondary cases occur on average at L + I/2

Where L: mean latency; I : mean Infectious period

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 Distribution of the Generation Interval
• Longer infectious periods leads to more secondary cases
More contacts during the infectious stage
latency
Infectious period Histogram of individual generation intervals
Provides the distribution of the GI
Infection of secondary case
P(GI = k) percentage of GI lasting k days

Different 2
primary
cases 3

Infection of primary case Days post infection

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 Average generation time

• Taking into account variability in the infectious period between, we obtain

GI = L + I/2 + σI2/2 I

• The average generation time depends on mean latency and infectious period, but
also on standard deviation of infectious period
• This is due longer infectious period having more secondary cases and more distant in time

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 Generation interval in common models
γI
• SIR : S I R

No latency : L=0
Sojourn time in I is exponentially distributed : I = 1/γ and standard deviation σI = 1/γ
Average GI = 1/γ (1/2I + σI2/2I = 1/2γ + (1/γ)2/ (2/γ) = 1/γ)
• SEIR : δE γI
S E I R

Average GI = 1/δ + 1/γ

• SEIR with split infectious period:
δE 2γ I 2γ I
S E I I R

Average I = 1/γ
Average GI = 1/δ + ¾ 1/γ

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 Intervals between successive cases (2)

Serial interval : The interval between a primary case symptoms

and symptoms of a secondary case
• Easy to observe
• A good proxy to the GI
• Same mean if incubation periods
remain similar between primary SI
and secondary cases
• Distributions are not the same.
Primary Case

Secondary Case

GI

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