Infectious Disease Epidemiology EPIET Introductory Course, 2006 Lazareto, 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

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

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 Reservoir Susceptible Host Agent Person to person transmission Reservoir Susceptible Host Portal of exit Portal of entry Agent Mode of transmission

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

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

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

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

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

Factors influencing disease transmission Agent Environment Host

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

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

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) 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

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

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

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

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

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

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

Sexual partners in last 12 months 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 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) Source: Natsal 2000

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

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

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 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 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 40% Infant vaccination introduced 1975 30% 20% % susceptible 10% 0% 1971-75 1980-81 1984-89 1990-91 Year data from Panagiotopoulos et al, BMJ, 1999

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

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

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

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

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