## **Natural history of a disease**

The natural history of a disease is how the disease progresses in an individual. 

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### **Incubation period**

The incubation period is the time from infection until symptoms occur. The incubation period can vary substantially between individuals. Factors that may influence the length of the incubation period include: route of transmission (eg: for HIV, whether infected sexually or from blood transfusion); transmission dose (the amount of the pathogen an individual is exposed to); characteristics of the infected individual (eg: age, partial immunity, or genetics); and interventions (eg: drugs).

The incubation period is often "right-skewed". This means that some individuals have a much longer incubation period than the median (see example below).[^1]

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### **Latent period**

The latent period is the time from infection until being infectious. Being infectious means being able to infect other individuals. The latent period is often highly correlated with the incubation period, however, it can be either longer or shorter.

### **Disease severity**

The severity of a disease, also known as its virulence, is how badly it affects individuals. It is normally measured by the proportion of infections that suffer a defined outcome. For example, the proportion of infections that are symptomatic; or the infection fatality rate (IFR), the proportion of infections that lead to death.

When reading about severity, it is important to consider the definition of both the outcome (the numerator) and how it is counted (the denominator). The numerator may vary in some cases, for example if the criteria for admission to hospital changes then the infection hospitalisation rate would change. The denominator will include all infections, only known cases, or some other definition.

## **Transmission**

### **Index case**

The first case identified in a population.

### **Primary infection**

The infection that introduces a pathogen into a population. The first primary infection in any human is known as "Patient Zero".

### **Secondary infection**

Infections directly from the primary infection. If secondary infections go on to infect further individuals, these are known as tertiary infections.

### **Infection attack rate**

The infection attack rate is the proportion of a group that is infected over the course of an epidemic.

### **Secondary attack rate**

The proportion of an infectious individual's contacts that become infected. Sometimes only includes susceptible contacts.

### **Serial interval**

The serial interval is the time between when an individual experiences symptoms and when individuals infected by them experience symptoms. If either of the infections are asymptomatic then it is not defined.

### **Generation time**

The generation time is the time between when an individual is infected, and when that individual infects someone else. The generation time is affected by both biological (eg: the length of the latent period) and behavioural factors (eg: if an individual isolates then they will not cause infections after that point).

The mean generation time is almost always equal to the mean serial interval. However, serial intervals are much easier to measure because symptom onsets are easy to observe. Therefore, the serial interval is often used as a proxy for the generation time.

A short generation time generally makes contact tracing harder. This is because the infection needs to be identified sooner to prevent onwards infection. 

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### **Basic reproduction number**

The basic reproduction number is the average number of secondary infections caused by a single primary infection when the entire population is susceptible (defined below). Also referred to as R0 or R0 (pronounced "R-nought"). R0 is affected by both the characteristics of the disease and the population. An epidemic with R0 < 1 will end without exponential growth. An epidemic with R0 > 1 has the potential to grow exponentially.

### **Effective reproduction number**

The effective reproduction number is defined at a specific time. It is the average number of infections caused by each infection at that time. It is generally lower than the basic reproduction number because it takes into account susceptible depletion (defined below). Also referred to as the "time-varying reproduction number", Rt, or simply the "reproduction number". If the effective reproduction number is less than 1, then the epidemic is decreasing in size; if the effective reproduction number is greater than 1, then the epidemic is increasing in size.

## **Epidemic progression**

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### **Exposure**

An exposure is an individual coming into contact with the pathogen (eg: a virus). Exposures can lead to infections, but are not guaranteed to.

### **Susceptibles**

Susceptibles, or susceptible individuals, are individuals without immunity to a disease. They could become infected if they are exposed to a pathogen.

### **Susceptible depletion**

Susceptible depletion means there are fewer susceptible individuals in a population. This is due to individuals gaining immunity through infection or vaccination. Fewer susceptible individuals in a population and makes it harder for the pathogen to spread.

### **Herd immunity**

Herd immunity is when there is enough susceptible depletion that the effective reproduction number is less than 1. The proportion of the population that needs to be immune for herd immunity is known as the herd immunity threshold. In the simple homogeneous \[SIR model]\(https://en.wikipedia.org/wiki/Compartmental_models_in\_epidemiology#:~:text=a given population.-,The SIR model,-[edit]), this is 1-(1/R0).

### **Overshoot**

Without interventions, an epidemic will infect more individuals than the herd immunity threshold. These additional infections are "overshoot". They occur in the declining part of the epidemic.

[^1]: For more detail on 'right-skewed' distributions, [see this 3-min blog post](https://medium.com/geekculture/what-are-right-skewed-and-left-skewed-distributions-a29b3def7598).


Common terminology in infectious disease epidemiology

Joshua Blake • October 21, 2024