1. Infectious Disease Epidemiology EPIET Introductory Course, 2006 Lazareto, Menorca
Prepared by: Mike Catchpole, Johan Giesecke, John Edmunds, Bernadette Gergonne

2. Epidemiology: Why Bother?
Human disease does not occur at random
Epidemiology leads to the identification of causal and preventive factors in human disease

3. Burden of disease in adult men and women, Established Market Economies: 1990
*Pertussis, polio, measles and tetanus
Source: World Bank

4. Epidemiology: basic concepts
The study of the distribution and determinants of disease frequency in (human) populations
Frequency
Distribution
Determinants

5. What is special about infectious disease epidemiology?

6. Specific concepts
Attack rate, immunity, vector, transmission, carrier, subclinical disease, serial interval, index case, source, exposure, reservoir, incubation period, colonization, generations, susceptible, non-specific immunity, clone, resistance, repeat episodes …
But why do we need these concepts?

7. Infectious disease: the unique factor
Infectious diseases can be spread from human to human (or animal to human)

8. Chain of Transmission Reservoir Susceptible Host Agent
Person to person transmission
Reservoir
Susceptible Host
Portal of exit
Portal of entry
Agent
Mode of transmission

9. Chain of transmission Reservoir Human Person with symptomatic illness
Carriers:
Asymptomatic
Incubating
Convalescent
Chronic
Animal: zoonosis
Environmental: soil, plant, water

10. Chain of transmission Mode of Transmission Direct Direct contact
Secretions, Blood, Faeces/urine
Droplet spread
Indirect
Food/water
Aerosol
Animal vectors
Fomites
Medical devices and treatments

11. Chain of transmission Portal of exit Human/animal Respiratory tract
Genito-Urinary tract
Faeces
Saliva
Skin (exanthema, cuts, needles, blood-sucking arthropods)
Conjunctival secretions
Placenta
Environmental
Cooling towers

12. Chain of transmission Portal of entry Respiratory tract
Mouth (faecal-oral transmission)
Skin
Mucous membranes
Blood

13. Level of disease occurence
Sporadic level: occasional cases occurring at irregular intervals
Endemic level: persistent occurrence with a low to moderate level
Hyperendemic level: persistently high level of occurrence
Epidemic or outbreak: occurrence clearly in excess of the expected level for a given time period
Pandemic: epidemic spread over several countries or continents, affecting a large number of people

14. What causes incidence to increase?
Portal of exit
Portal of entry
Agent
Susceptible Host
Mode of transmission
Reservoir

15. Why does an epidemic occur ?
Agent and host in adequate number
Recent increase in amount of the agent
Recent increase in infectivity / virulence of the agent
Recent introduction of the agent
Enhanced mode of transmission
Increase of host exposure
Change in the susceptibility of the host response to the agent
Introduction through new portals of entry

16. Factors influencing disease transmission
Agent
Environment
Host

17. Factors influencing disease transmission
Agent
Environment
Infectivity
Pathogenicity
Virulence
Immunogenicity
Antigenic stability
Survival
Weather
Housing
Geography
Occupational setting
Air quality
Food
Age
Sex
Genotype
Behaviour
Nutritional status
Health status
Host

18. Infectious Disease Epidemiology: five major differences
A case can also be an exposure
Sub-clinical infections influence epidemiology
Contact patterns play major role
Immunity
There is sometimes a need for urgency

19. 1. Case = exposure Unique to infectious disease epidemiology.
Usually, the sets of exposures and outcomes are completely apart e.g. smoking and cancer.

20. The average number of cases an infectious individual will generate
Dependent on 4 factors:
1) The number of contacts made (c)
2) The probability of infection given contact (p)
3) The duration of infectiousness (D)
4) The proportion of contacts who are susceptible (S)

21. The basic reproduction number, R0
Useful summary statistic
Definition:
the average number of secondary cases a typical infectious individual will cause in a completely susceptible population
Measure of the intrinsic potential for an infectious agent to spread

22. The basic reproduction number, R0
If everyone is susceptible then the average number of secondary infections generated by a single infectious individual is given by:
R0 = p x c x D
Can be estimated if we know p, c, & D, or from proportion susceptible, outbreaks in susceptible populations, the average age at infection (and many other ways)

23. R0, threshold for invasion
If R0 < 1 then infection cannot invade a population
implications: infection control mechanisms unnecessary (therefore not cost-effective)
If R0 > 1 then (on average) the pathogen will invade that population
implications: control measure necessary to prevent (delay) an epidemic

24. After invasion: the effective reproduction number, R(t)
Initial invasion, R(t) = R0
As pathogen invades, the number of susceptibles declines through recovery (or death)
Eventually, insufficient susceptibles to maintain chains of transmission
On average each infectious person infects < 1 other, epidemic dies out
Peak of epidemic R(t) = 1

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

26. Determinants of STI incidence=
p c D
p Risk of transmission
c Rate of sexual partner change
D Duration of infectivity 7

27. STI Control Strategies=
p c D
p condoms, acyclovir, zidovudine
c health education, negotiating skills
D case ascertainment (screening,
partner notification), treatment,
compliance, health seeking behaviour, accessibility of services 8

28. Cases of Gonorrhoea and Genital Herpes seen in STI clinics in England, 1971-1999

29. Determinants of STD incidence
cT = 1
pD
cT Critical threshold for maintenance
p Risk of transmission
D Duration of infectivity 9

30. Sexual partners in last 12 months*
* UK National Study of Sexual Attitudes and Lifestyles

31. Sexual partners in last 12 months
cHerpes
cGC

32. 2. Subclinical infections
R0 = p x c x D
A case can be a case without being recognised as a case.
What do we mean by ´asymptomatic´?
How do recognise these?
What level of infectious risk do they pose?

33. Asymptomatic Infections
Genital Chlamydia trachomatis infection
% infected women asymptomatic
Poliomyelitis
- 90% asymptomatic or non-specific fever
HIV
- majority asymptomatic or non-specific symptoms pre-AIDS
SARS-CoV
- ??

34. Rates of genital chlamydial infection in the general population, UK 2000
Adj OR 0.58 ( )
Adj OR 0.43 ( )
Adj OR 1.37 ( )
Adj OR 0.90 ( )
Source: Natsal 2000

35. Undiagnosed HIV Infection Among Men Who Have Sex With Men, STI Clinic Attendees, London 2003

36. 3. Contact patterns R0 = p x c x D
Do all cases contribute equally to the spread of disease?
How can we identify and control 'super spreaders'?

37. SARS, Inner Mongolia

38. Small world
How big probability that there is a sexual chain between two random people?
'Six degrees of separation'
Do people choose sexual partner at random?
If not, how does this affect epidemiology?

39. Reported new sexual partners from outside the UK in the past 5 years, by gender and age-group
Source: Natsal 2000

41. 4. Immunity R0 = p x c x D Can we measure it?
How can we change it (positively or negatively)?
Can we predict the consequences of changing immunity?

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

43. Consequences of Changing Immunity
Not always what you might intuitively expect

44. Proportion of pregnant women susceptible to rubella
Athens,
40%
Infant vaccination
introduced 1975
30%
20%
% susceptible
10% 0%
Year
data from Panagiotopoulos et al, BMJ, 1999

45. Age distribution of outpatient rubella cases, Athens
40%
1986 (n=113)
1993 (n=326)
30%
20%
Proportion of cases
10% 0%
0-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40+
Age group
from Panagiotopoulos et al, BMJ, 1999

46. Rubella and CRS in Greece, 1993
3000
Rubella notifications 8
CRS cases 7
2500 6
2000 5
1500 4
Rubella Notifications
CRS cases 3
1000 2
500 1
Jan
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
Month

47. 5. A need for urgency
R0 = p x c x D
What EPIET is very much about…

48. Five major differences
A case can also be an exposure
Sub-clinical infections influence epidemiology
Contact patterns play major role
Immunity
There is sometimes a need for urgency

49. If you enjoyed this… Further reading: McNeill, WH. Plagues and Peoples
Diamond J. Guns, Germs, and Steel: The fates of human societies.