Infectious Disease Epidemiology

EPIET Introductory Course, 2006Lazareto, Menorca

Prepared by: Mike Catchpole, Johan Giesecke, John Edmunds, Bernadette Gergonne

Epidemiology: Why Bother?

Human disease does not occur at random

Epidemiology leads to the identification of causal and preventive factors in human disease

-1500 -1000 -500 0 500 1000 1500

Respiratory infections

Hepatitis

Meningitis

Childhood cluster*

Diarrhoeal disease

HIV

STDs (excluding HIV)

Tuberculosis

Thousands of DALYS lost

Women Men

Burden of disease in adult men and women, Established Market

Economies: 1990

Source: World Bank

*Pertussis, polio, measles and tetanus

Epidemiology: basic concepts

The study of the distribution and determinants of disease frequency in (human) populations

• Frequency • Distribution• Determinants

What is special about infectious disease epidemiology?

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?

Infectious disease: the unique factor

Infectious diseases can be spread from human to human

(or animal to human)

Chain of Transmission

Portal of exit

Portal of entry

Agent

Susceptible Host

Mode of transmission

ReservoirPerson to person transmission

Chain of transmission

Reservoir

Human

Person with symptomatic illness

Carriers:

Asymptomatic

Incubating

Convalescent

Chronic

Animal: zoonosis

Environmental: soil, plant, water

Chain of transmission

Direct

Direct contact

Secretions, Blood, Faeces/urine

Droplet spread

Indirect

Food/water

Aerosol

Animal vectors

Fomites

Medical devices and treatments

Mode of Transmission

Chain of transmission

Human/animal

Respiratory tract

Genito-Urinary tract

Faeces

Saliva

Skin (exanthema, cuts, needles, blood-sucking arthropods)

Conjunctival secretions

Placenta

Environmental

Cooling towers

Portal of exit

Respiratory tract

Mouth (faecal-oral transmission)

Skin

Mucous membranes

Blood

Portal of entry

Chain of transmission

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

What causes incidence to increase?

Portal of exit

Portal of entry

Agent

Susceptible Host

Mode of transmission

Reservoir

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

Host

Agent Environment

Factors influencing disease transmission

Agent

Host

Environment

• Age

• Sex

• Genotype

• Behaviour

• Nutritional status

• Health status

• Infectivity

• Pathogenicity

• Virulence

• Immunogenicity

• Antigenic stability

• Survival

• Weather

• Housing

• Geography

• Occupational setting

• Air quality

• Food

Factors influencing disease transmission

Infectious Disease Epidemiology: five major differences

1. A case can also be an exposure

2. Sub-clinical infections influence epidemiology

3. Contact patterns play major role

4. Immunity

5. There is sometimes a need for urgency

1. Case = exposure

Unique to infectious disease epidemiology.

Usually, the sets of exposures and outcomes are completely apart e.g. smoking and cancer.

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)

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

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)

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

After invasion: the effective reproduction number, R(t)

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

Initial invasion, R(t) = R0

Peak of epidemic R(t) = 1

Changes to R(t), over an epidemic

0

200

400

600

800

1000

1200

0 0,05 0,1 0,15 0,2

time

nu

mb

er

Susceptible

Incident cases

Recovered

R=R0

R>1

R=1

R<1

Determinants of STI incidence

R0 = p c D

p Risk of transmission

c Rate of sexual partner change

D Duration of infectivity

STI Control Strategies

R0 = 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

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

0

20000

40000

60000

80000

Year

Num

ber

of C

ases

Genital Herpes

Gonorrhoea

Determinants of STD incidence

cT = 1 pD

cT Critical threshold for maintenance

pRisk of transmission

D Duration of infectivity

Sexual partners in last 12 months*

0

0,05

0,1

0,15

0,2

0,25

0,3

0,35

0,4

0 1 2 3 4 5

Number of partners

Pro

port

ion

of p

opul

atio

n

* UK National Study of Sexual Attitudes and Lifestyles

Sexual partners in last 12 months

0

0,05

0,1

0,15

0,2

0,25

0,3

0,35

0,4

0 1 2 3 4 5

Number of partners

Pro

port

ion

of p

opu

latio

n cHerpes cGC

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?

Asymptomatic Infections

Genital Chlamydia trachomatis infection- 50-70% infected women asymptomatic

Poliomyelitis- 90% asymptomatic or non-specific fever

HIV- majority asymptomatic or non-specific symptoms pre-AIDS

SARS-CoV- ??

Rates of genital chlamydial infection in the general population, UK 2000

0

0,5

1

1,5

2

2,5

3

3,5

18-24 25-34 35-44 All

Age group

Pre

va

len

ce

Men

Women

Adj OR 0.58 (0.18-1.85)Adj OR 0.43 (0.13-1.39)

Adj OR 1.37 (0.47-4.00)Adj OR 0.90 (0.36-2.29)

0

1

2

3

4

5

16-17 18-19 20-24 25-29 30-34 35-39 40-44Age group

Pre

vale

nc

e

Men

Women

Source: Natsal 2000

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

0%

20%

40%

60%

80%

100%

All MSM MSM with STI

Undiagnosed HIVinfectionAnonymously testedfor HIV

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'?

SARS, Inner Mongolia

Meng 157

Tongs

Vis 283 Vis 242 Pt 168 Rel 164 Rel 160 Rel 161 Rel 165 HCW 241

Acq 285 Acq 88 HCW 78 Vis 284 Rel 243 HCW 100 HCW 245

Acq 176 Vis 238 Rel 98 Rel 75 Rel 259 Rel 85

Thoracic Hospital

HCW 183 HCW 175 HCW 84 HCW 267 HCW 141 HCW 137

Inner Mongolia Hospital

HCW 250 HCW 255

abr-21 abr-24

abr-12abr-12

abr-25

abr-16 abr-25 abr-13abr-12

abr-24

abr-16abr-19abr-11

abr-21

abr-03

abr-18

abr-18

abr-29 abr-30

abr-02abr-01

abr-07

mar-30 mar-31

abr-11abr-16

mar-19

mar-26 mar-27 mar-30

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?

Reported new sexual partners from outside the UK in the past 5 years, by gender and age-group

0

5

10

15

20

25

16-24 25-34 35-44 All agegroups

Age Group

Per

cen

tag

e

Men

Women

Source: Natsal 2000

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?

Vaccination coverage required for elimination

0%

20%

40%

60%

80%

100%

0 2 4 6 8 10 12 14 16 18 20

Basic reproduction number, Ro

Critic

al pro

portio

n, Pc

Pc = 1-1/Ro

rubella measles

Consequences of Changing Immunity

Not always what you might intuitively expect

Proportion of pregnant women susceptible to rubella

Athens, 1975-91

0%

10%

20%

30%

40%

1971-75 1980-81 1984-89 1990-91

Year

% s

usc

epti

ble

Infant vaccination introduced 1975

data from Panagiotopoulos et al, BMJ, 1999

Age distribution of outpatient rubella cases, Athens

0%

10%

20%

30%

40%

0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40+

Age group

Pro

po

rtio

n o

f ca

ses

1986 (n=113)

1993 (n=326)

from Panagiotopoulos et al, BMJ, 1999

Rubella and CRS in Greece, 1993

0

500

1000

1500

2000

2500

3000

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

Month

Ru

bel

la N

oti

fica

tio

ns

0

1

2

3

4

5

6

7

8

CR

S c

ases

CRS cases

Rubella notifications

5. A need for urgency

R0 = p x c x D

What EPIET is very much about…

Five major differences

1. A case can also be an exposure

2. Sub-clinical infections influence epidemiology

3. Contact patterns play major role

4. Immunity

5. There is sometimes a need for urgency

If you enjoyed this…

Further reading:

McNeill, WH. Plagues and Peoples

Diamond J. Guns, Germs, and Steel: The fates of human societies.