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? Cause outbreaks High numbers Mortality, morbidity Can create panic and high costs Treatment can become difficult (resistance)

Which are the most important infections in the EU? GI: noro, sal, campy Resp: flu, TB VPD: measles HAIC: MRSA, Cdiff HIV

New kids on the block BSE nvCJD TSS Chikungunya Hanta HEV H5N1 EHEC West Nile Lyme HCV HIV SARS

Infectious vs. non-infectious disease epidemiology Same general rationale terminology (mostly) study methods ways of collecting data blood samples, questionnaires, registries … analysis (statistics) Infectious disease epidemiology has the same general conceptual framework as ‘non-infectious disease’ epidemiology, and still seeks to understand the causes and distribution of disease in populations with the aim of controlling disease The same terminology is used (mostly, we will introduce a few different terms later) Same methods used for analysis (again, some exceptions such as transmission dynamic modelling) Same ways of collecting data…

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 Secondary cases 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

Person-to-person transmission Chain of Transmission Reservoir Portal of exit Agent Portal of entry Susceptible host Person-to-person transmission

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 Mucous to mucous = STI, feacal-oral (HAV, shigella) Placentar = toxoplasmosis Transplants, blood = HBV Skin to skin Herpes Type 1 Sneezes, cough: influenza Waterborne = cryptosporidium, giardia Airborne = varicella Foodborne= salmon Vector= malaria, WNV Objects = scarlet fever, norovirus Most pathogens for indirect transmission also can be directly transmitted Exceptions?? Anthrax, legionella

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

Dynamics of disease and infectiousness Latent period Infectious period Non-infectious period Incubation period Clinical disease Recovery Onset of symptoms Resolution of symptoms Infection Time

Relationships between time periods Transmission Second patient Latent period Infectious period Incubation period Clinical disease Transmission First patient Latent period Infectious period Example: hepatitis A Incubation period Clinical disease Serial interval or generation time Infection Time Infection

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 Sporadic: botulism Endemic: measles Epidemic Pandemic: HIV, flu

Person-to-person transmission What causes incidence to increase? Reservoir Portal of exit Agent Portal of entry Susceptible host Person-to-person transmission

Factors influencing disease transmission Climate change Megacities Pollution Agent Animals Environment Vectors Vector proliferation Vector resistance Food production Intensive farming Antibiotics Infectivity Pathogenicity Virulence Immunogenicity Antigenic stability Population growth Migration Behaviour

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 Example in history: Europeans came into contact with Americans natives. Many of them died of polio. Or SARS…

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 R0 Average age at infection* Measles 11-18 4-5 Pertussis 16-18 Mumps 11-14 6-7 Rubella 6-12 6-10 Diphtheria Polio 12-17 The basic reproduction number of several childhood infections is shown here. Measles and Pertussis have a particularly high R0. You can also see here how R0 is related to the average age at infection. The higher R0, the lower the average age at infection. Source: Anderson & May, 2006 * In the absence of immunization

Imagine that one infectious individual is introduced into a susceptible population. He/she then infects 3people, who in turn infect 3 others (what is the R0 for this infection?). This leads to an exponential increase in the number of cases (which will be limited by pop size).

If some individuals in the population are immune, then the infection cannot spread so rapidly.. Because the chains of transmission stop on encounter with an immune individual, others further down the chain (who may or may not be immune) are protected (dotted arrows). Note that when the population is not entirely susceptible, we measure transmission by the ‘effective reproduction number’ , which in this case is one. The infection is endemic – to eradicate the infection the effective reproduction number must be brought below one.

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 = R0 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 R=R0

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

Please talk to the person next to you. 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? Vaccinations Condoms Face mask Hygiene Isolation, quarantine Early detection/treatment

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 Pc = 1-1/Ro rubella measles

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; 192-195 Heymann D, Control of Communicable Diseases Manual, 19th ed. 2008 McNeill, WH. Plagues and Peoples, 3rd ed. 1998