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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 BSE TSS EHEC Lyme HIV nvCJD HEV HCV Hanta Chikungunya H5N1 West Nile SARS H1N1 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-toperson transmission Portal of exit Susceptible host Agent Portal of entry 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 Indirect transmission Mucous to mucous membrane Waterborne Across placenta Airborne Transplants, blood Foodborne Skin to skin Vectorborne Sneezes, cough Objects/Fomites Possible outcomes after exposure to an infectious agent Exposure No infection Death Clinical infection Immunity Subclinical infection Carriage Carriage Non-immunity Dynamics of disease and infectiousness Latent period Infectious period Incubation period Infection Clinical disease Onset of symptoms Non-infectious period Recovery Resolution of symptoms Time Relationships between time periods Transmission Second patient Latent period Infectious period Incubation period First patient Transmission Latent period Incubation period Infection Clinical disease Infectious period Clinical disease 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-toperson transmission Portal of exit Susceptible host Agent Portal of entry Factors influencing disease transmission Climate change Megacities Pollution Vector proliferation Environment Vector resistance Vectors Animals Food production Agent Intensive farming Antibiotics Infectivity Pathogenicity Virulence Immunogenicity Population growth Migration Behaviour 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 (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↓ 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 • (1+2+0+1+3+2+1+2+1+2)/10 = 1.5 – R0 < 1 - the disease will disappear – R0 = 1 - the disease will become endemic – R0 > 1 - there will be an epidemic Approximate formula for R0 • For childhood diseases: R0 = 1 + L/A – L - average life span in the population – A - average age at infection R0 of childhood diseases Infection/ infectious agent Measles 11-18 Average age at infection* 4-5 Pertussis 16-18 4-5 Mumps 11-14 6-7 Rubella 6-12 6-10 Diphtheria 4-5 11-14 Polio 6-7 12-17 Source: Anderson & May, 2006 R0 * In the absence of immunization 800 number of cases 700 600 500 400 300 200 100 0 1 2 3 4 generation 5 6 7 800 number of cases 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 • 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 Initial phase R = R0 Peak of epidemic R = 1 Changes to R(t) over an epidemic 1200 number 1000 800 600 Susceptible Incident cases Immune R=1 400 R<1 R>1 R=R0 200 0 0 0.05 0.1 time 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/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 Vaccination coverage required for elimination Critical proportion, Pc 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 0 2 4 6 8 10 12 14 16 Basic reproduction number, Ro measles 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, 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; 192195 • Heymann D, Control of Communicable Diseases Manual, 19th ed. 2008 • McNeill, WH. Plagues and Peoples, 3rd ed. 1998