Infectious Disease Epidemiology

EPIET Introductory Course, 2011 Lazareto, Menorca, Spain

Mike Catchpole, Bernadette Gergonne, James Stuart, Outi Lyytikäinen, Viviane Bremer

Objective

to review importance and specific concepts of infectious disease epidemiology

Why are infections important?

Which are the most important infections in the EU?

New kids on the block

TSS EHEC Lyme HIV BSE HEV HCV Hanta nvCJD H5N1 West Nile Chikungunya H1N1 SARS

Infectious vs. non-infectious disease epidemiology

• • • • •

Same

general rationale terminology (mostly) study methods ways of collecting data – blood samples, questionnaires, registries … analysis (statistics)

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

Case = exposure

• • • • • Primary case – 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

Chain of Transmission

Reservoir

Person-to person transmission Portal of exit

Susceptible host

Portal of entry

Agent

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

Transmission routes

Direct transmission

Mucous to mucous membrane Across placenta Transplants, blood Skin to skin Sneezes, cough

Indirect transmission

Waterborne Airborne Foodborne Vectorborne Objects/Fomites

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

Dynamics of disease and infectiousness Infection

Latent period Infectious period Incubation period Clinical disease Non-infectious period Recovery

Onset of symptoms Resolution of symptoms Time

Relationships between time periods

Second patient Transmission

Latent period Infectious period Incubation period Clinical disease

First patient

Latent period

Transmission

Infectious period Incubation period Clinical disease

Infection

Serial interval or generation time

Time

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

What causes incidence to increase?

Reservoir

Person-to person transmission Portal of exit

Susceptible host

Portal of entry

Agent

Factors influencing disease transmission Climate change Megacities Pollution Environment Vector proliferation Vector resistance Vectors Animals Food production Intensive farming Antibiotics

Agent

Population growth Migration Behaviour Infectivity Pathogenicity Virulence Immunogenicity Antigenic stability

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

Basic reproductive rate (R

0

)

• • • Basic formula for the actual value: R 0 = 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 ↓

Basic reproductive rate (R

0

)

• • 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 (1+2+0+1+3+2+1+2+1+2)/10 = 1.5

– R 0 < 1 - the disease will disappear – R 0 = 1 - the disease will become endemic – R 0 > 1 - there will be an epidemic

Approximate formula for R

0

• For childhood diseases: R 0 = 1 + L/A – L - average life span in the population – A - average age at infection

R

0

of childhood diseases

Infection/ infectious agent

Measles Pertussis Mumps Rubella Diphtheria Polio Source: Anderson & May, 2006

R 0

11-18 16-18

Average age at infection*

4-5 4-5 11-14 6-12 4-5 6-7 6-7 6-10 11-14 12-17 * In the absence of immunization

800 700 600 500 400 300 200 100 0 1 2 3 4 generation 5 6 7

800 700 600 500 400 300 200 100 0 1 2 3 4 generation 5 6 7

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.

• • •

Effective reproduction number R

Initial phase R = R 0 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

Changes to R(t) over an epidemic

1200 1000 800 600 400 200 0 0

R=R 0 R>1 R=1

0.05

R<1

0.1

time Susceptible Incident cases Immune 0.15

0.2

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

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?

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

Herd immunity threshold

Minimum proportion (p) of population that needs to be immunized in order to obtain herd immunity p > 1 - 1/R 0 e.g. if R 0 = 3, immunity threshold = 67% if R 0 = 16, immunity threshold = 94% Important concept for immunization programs and eradication of an infectious disease

Vaccination coverage required for elimination

Pc = 1-1/Ro 1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

rubella measles 0 2 4 6 8 10 12 14 Basic reproduction number, Ro 16 18 20

Key points

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

If you enjoyed this…

• • • • • Anderson RM & May RM, Infectious Diseases of Humans: Dynamics and Control, 11 th ed. 2006 Giesecke J, Modern Infectious Disease Epidemiology, 2 nd ed. 2002 Barreto ML, Teixeira MG, Carmo EH. Infectious diseases epidemiology. J Epidemiol Community Health 2006; 60; 192 195 Heymann D, Control of Communicable Diseases Manual, 19 th ed. 2008 McNeill, WH. Plagues and Peoples, 3 rd ed. 1998