1. Infectious Disease Epidemiology
EPIET Introductory Course, 2011 Lazareto, Menorca, Spain
Mike Catchpole, Bernadette Gergonne, James Stuart, Outi Lyytikäinen, Viviane Bremer

2. Objective
to review importance and specific concepts of infectious disease epidemiology

3. Why are infections important?
Cause outbreaks
High numbers
Mortality, morbidity
Can create panic and high costs
Treatment can become difficult (resistance)

4. Which are the most important infections in the EU?
GI: noro, sal, campy
Resp: flu, TB
VPD: measles
HAIC: MRSA, Cdiff
HIV

5. New kids on the block BSE nvCJD TSS Chikungunya Hanta HEV H5N1 EHEC
West Nile
Lyme
HCV
HIV
SARS

6. Infectious vs. non-infectious disease epidemiology
Same
general rationale
terminology (mostly)
study methods
ways of collecting data
blood samples, questionnaires, registries …
analysis (statistics)
Infectious disease epidemiology has the same general conceptual framework as ‘non-infectious disease’ epidemiology, and still seeks to understand the causes and distribution of disease in populations with the aim of controlling disease
The same terminology is used (mostly, we will introduce a few different terms later)
Same methods used for analysis (again, some exceptions such as transmission dynamic modelling)
Same ways of collecting data…

7. But some special features
A case may also be a risk factor
Person with infection can also be source of infection
People may be immune
Having had an infection or disease could result to resistance to an infection (immunity)
A case may be a source without being recognized
Asymptomatic/sub-clinical infections
There is sometimes a need for urgency
Epidemics may spread fast and require control measures
Preventive measures (usually) have a good scientific evidence

8. Case = exposure Primary case Secondary cases
Person who brings the disease/infection into a population
Secondary cases
Persons who are infected by primary case
Generation of infections (waves)
Secondary cases are infected at about the same time and consequently tertiary cases
Index case
First case discovered during an outbreak
Reproductive rate
Potential of disease to spread in a population

9. Person-to-person transmission
Chain of Transmission
Reservoir
Portal of exit
Agent
Portal of entry
Susceptible host
Person-to-person transmission

10. Reservoir and source of infection
Reservoir of infection
Ecological niche where the infectious agent survives and multiplies
Person, animal, arthropod, soil, or substance
Source
Human
Animal
Environment

11. Transmission routes Direct transmission Indirect transmission
Mucous to mucous membrane
Waterborne
Across placenta
Airborne
Transplants, blood
Foodborne
Skin to skin
Vectorborne
Sneezes, cough
Objects/Fomites
Mucous to mucous = STI, feacal-oral (HAV, shigella)
Placentar = toxoplasmosis
Transplants, blood = HBV
Skin to skin Herpes Type 1
Sneezes, cough: influenza
Waterborne = cryptosporidium, giardia
Airborne = varicella
Foodborne= salmon
Vector= malaria, WNV
Objects = scarlet fever, norovirus
Most pathogens for indirect transmission also can be directly transmitted
Exceptions?? Anthrax, legionella

12. Possible outcomes after exposure to an infectious agent
No infection
Clinical infection
Subclinical infection
Carriage
Death
Immunity
Carriage
Non-immunity

13. Dynamics of disease and infectiousness
Latent period
Infectious period
Non-infectious period
Incubation period
Clinical disease
Recovery
Onset of symptoms
Resolution of symptoms
Infection
Time

14. Relationships between time periods
Transmission
Second patient
Latent period
Infectious period
Incubation period
Clinical disease
Transmission
First patient
Latent period
Infectious period
Example: hepatitis A
Incubation period
Clinical disease
Serial interval
or generation time
Infection
Time
Infection

15. Disease occurrence in populations
Sporadic
Occasional cases occurring at irregular intervals
Endemic
Continuous occurrence at an expected frequency over a certain period of time and in a certain geographical location
Epidemic or outbreak
Occurrence in a community or region of cases of an illness with a frequency clearly in excess of normal expectancy
Pandemic
Epidemic involves several countries or continents, affecting a large population
Sporadic: botulism
Endemic: measles
Epidemic
Pandemic: HIV, flu

16. Person-to-person transmission
What causes incidence to increase?
Reservoir
Portal of exit
Agent
Portal of entry
Susceptible host
Person-to-person transmission

17. Factors influencing disease transmission
Climate change
Megacities
Pollution
Agent
Animals
Environment
Vectors
Vector proliferation
Vector resistance
Food production
Intensive farming
Antibiotics
Infectivity
Pathogenicity
Virulence
Immunogenicity
Antigenic stability
Population growth
Migration
Behaviour

18. Reproductive rate
Potential of an infectious disease to spread in a population
Dependent on 4 factors:
Probability of transmission in a contact between an infected individual and a susceptible one
Frequency of contacts in the population - contact patterns in a society
Duration of infectiousness
Proportion of the population/contacts that are already immune, not susceptible

19. Basic reproductive rate (R0)
Basic formula for the actual value: R0 = β * κ * D
β - risk of transmission per contact (i.e. attack rate)
Condoms, face masks, hand washing  β ↓
κ - average number of contacts per time unit
Isolation, closing schools, public campaigns  κ ↓
D - duration of infectiousness measured by the same time units as κ
Specific for an infectious disease
Early diagnosis and treatment, screening, contact tracing  D ↓

20. Basic reproductive rate (R0)
Average number of individuals directly infected by an infectious case (secondary cases) during her or his entire infectious period, when she or he enters a totally susceptible population
( )/10 = 1.5
R0 < 1 - the disease will disappear
R0 = 1 - the disease will become endemic
R0 > 1 - there will be an epidemic
Example in history: Europeans came into contact with Americans natives. Many of them died of polio.
Or SARS…

21. Approximate formula for R0
For childhood diseases: R0 = 1 + L/A
L - average life span in the population
A - average age at infection

22. R0 of childhood diseases
Infection/ infectious agent R0
Average age at infection*
Measles
11-18
4-5
Pertussis
16-18
Mumps
11-14
6-7
Rubella
6-12
6-10
Diphtheria
Polio
12-17
The basic reproduction number of several childhood infections is shown here. Measles and Pertussis have a particularly high R0. You can also see here how R0 is related to the average age at infection. The higher R0, the lower the average age at infection.
Source: Anderson & May, 2006
* In the absence of immunization

23. Imagine that one infectious individual is introduced into a susceptible population. He/she then infects 3people, who in turn infect 3 others (what is the R0 for this infection?). This leads to an exponential increase in the number of cases (which will be limited by pop size).

24. If some individuals in the population are immune, then the infection cannot spread so rapidly.. Because the chains of transmission stop on encounter with an immune individual, others further down the chain (who may or may not be immune) are protected (dotted arrows). Note that when the population is not entirely susceptible, we measure transmission by the ‘effective reproduction number’ , which in this case is one. The infection is endemic – to eradicate the infection the effective reproduction number must be brought below one.

25. Effective reproduction number R
If the population is not fully susceptible, the average number of secondary cases is less than Ro. This is the effective reproduction number.

26. Effective reproduction number R
Initial phase R = R0
Epidemic in susceptible population
Number of susceptibles starts to decline
Eventually, insufficient susceptibles to maintain transmission. When each infectious person infects <1 persons, epidemic dies out
Peak of epidemic R = 1

27. Changes to R(t) over an epidemic
R=R0

28. R, threshold for invasion
If R < 1
infection cannot invade a population
implications: infection control mechanisms unnecessary (therefore not cost-effective)
If R > 1
on average the pathogen will invade that population
implications: control measure necessary to prevent (delay) an epidemic

29. Please talk to the person next to you.
What control measures might reduce the average number of cases an infectious individual will generate?
Please talk to the person next to you.
Can you think of one or two examples?
Vaccinations
Condoms
Face mask
Hygiene
Isolation, quarantine
Early detection/treatment

30. Herd immunity
Level of immunity in a population which prevents epidemics even if some transmission may still occur
Presence of immune individuals protects those who are not themselves immune

31. Herd immunity threshold
Minimum proportion (p) of population that needs to be immunized in order to obtain herd immunity p > 1 - 1/R0 e.g. if R0 = 3, immunity threshold = 67% if R0 = 16, immunity threshold = 94% Important concept for immunization programs and eradication of an infectious disease

32. Vaccination coverage required for elimination
Pc = 1-1/Ro
rubella
measles

33. Key points
No question about continuing and increasing threat from infections
Infectious disease epidemiology is different
Transmission dynamics important for prevention and control

34. If you enjoyed this…
Anderson RM & May RM, Infectious Diseases of Humans: Dynamics and Control, 11th ed. 2006
Giesecke J, Modern Infectious Disease Epidemiology, 2nd ed. 2002
Barreto ML, Teixeira MG, Carmo EH. Infectious diseases epidemiology. J Epidemiol Community Health 2006; 60;
Heymann D, Control of Communicable Diseases Manual, 19th ed. 2008
McNeill, WH. Plagues and Peoples, 3rd ed. 1998