Epidemiology of Infectious Diseases Mehmet Tevfik DORAK MD

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Epidemiology of Infectious Diseases Mehmet Tevfik DORAK, MD Ph. D School of Life Sciences,

Epidemiology of Infectious Diseases Mehmet Tevfik DORAK, MD Ph. D School of Life Sciences, Pharmacy & Chemistry Kingston University London 20 May 2020

Infectious Disease Epidemiology: Unique Features • • • A case can also be an

Infectious Disease Epidemiology: Unique Features • • • A case can also be an exposure Subclinical infections influence epidemiology Contact patterns play major role Immunity There is sometimes a need for urgency

What is Infectious Disease Epidemiology? Epidemiology • Deals with one population • Risk �case

What is Infectious Disease Epidemiology? Epidemiology • Deals with one population • Risk �case • Identifies causes Infectious disease epidemiology v Two or more populations v A case is a risk factor v The cause is often known

What is Infectious Disease Epidemiology? Two or more populations v. Humans v. Infectious agents

What is Infectious Disease Epidemiology? Two or more populations v. Humans v. Infectious agents v. Helminths, bacteria, fungi, protozoa, viruses, prions v. Vectors v. Mosquito (protozoa-malaria), snails (helminthsschistosomiasis) v. Blackfly (microfilaria-onchocerciasis) – bacteria? v. Animals v. Dogs and sheep/goats – Echinococcus v. Mice and ticks – Borrelia

What is Infectious Disease Epidemiology? A case is a risk factor … v. Infection

What is Infectious Disease Epidemiology? A case is a risk factor … v. Infection in one person can be transmitted to others

What is Infectious Disease Epidemiology? The cause often known v An infectious agent is

What is Infectious Disease Epidemiology? The cause often known v An infectious agent is a necessary cause What is infectious disease epidemiology used for? v Identification of causes of new, emerging infections, e. g. HIV, SARS, COVID-19 v Surveillence of infectious disease v Identification of source of outbreaks v Studies of routes of transmission and natural history of infections v Identification of new interventions

Concepts Specific to Infectious Disease Epidemiology Attack rate, immunity, vector, transmission, carrier, subclinical disease,

Concepts Specific to Infectious Disease Epidemiology Attack rate, immunity, vector, transmission, carrier, subclinical disease, serial interval, index case, source, exposure, reservoir, incubation period, colonization, generations, susceptible, non-specific immunity, herd immunity, clone, resistance, repeat episodes …

Infectious Disease Definitions v Infectious diseases Tetanus Measles v. CJD v Caused by an

Infectious Disease Definitions v Infectious diseases Tetanus Measles v. CJD v Caused by an infectious agent v Communicable diseases v Transmission – directly or indirectly – from an infected person v Transmissible diseases v Transmission – through unnatural routes – from an infected person Note v Infections are often subclinical – infections vs infectious diseases! v Antonyms not well-defined v Non-communicable diseases – virus involved in pathogenesis of diabetes? v Chronic diseases – HIV?

Routes of transmission Direct Indirect v Skin-skin v Herpes type 1 v Mucous-mucous v

Routes of transmission Direct Indirect v Skin-skin v Herpes type 1 v Mucous-mucous v Food-borne v STI v Across placenta v Toxoplasmosis v Through breast milk v HIV v Salmonella v Water-borne v Hepatitis A v Vector-borne v Malaria v Air-borne v Chickenpox v Sneeze-cough v Influenza Exposure v A relevant contact – depends on the agent v Skin, sexual intercourse, water contact, etc

Some Pathogens that Cross the Placenta

Some Pathogens that Cross the Placenta

Modes of Disease Transmission

Modes of Disease Transmission

Exposure to Infectious Agents No infection Death Clinical Carrier Sub-clinical Immunity Outcome Carrier No

Exposure to Infectious Agents No infection Death Clinical Carrier Sub-clinical Immunity Outcome Carrier No immunity

Dynamics of infectiousness Susceptible Infection Timeline for Infection Latent period Infectious period Non-infectious Dynamics

Dynamics of infectiousness Susceptible Infection Timeline for Infection Latent period Infectious period Non-infectious Dynamics of disease Susceptible Infection Time Incubation period Symptomatic period Non-diseased Time

Transmission Cases v Index – the first case identified v Primary – the case

Transmission Cases v Index – the first case identified v Primary – the case that brings the infection into a population v Secondary – infected by a primary case v Tertiary – infected by a secondary case T S Susceptible Immune Sub-clinical Clinical P S S T

Person-to-Person Transmission Data from Dr. Simpson’s studies in England (1952) Measles Chickenpox Rubella Children

Person-to-Person Transmission Data from Dr. Simpson’s studies in England (1952) Measles Chickenpox Rubella Children exposed Children ill 251 201 238 172 218 82 Attack rate 0. 80 0. 72 0. 38 Attack rate = ill exposed

Epidemiologic Triad Disease is the result of forces within a dynamic system consisting of:

Epidemiologic Triad Disease is the result of forces within a dynamic system consisting of: agent of infection host environment

Factors Influencing Disease Transmission Agent Environment • Infectivity • Weather • Pathogenicity • Housing

Factors Influencing Disease Transmission Agent Environment • Infectivity • Weather • Pathogenicity • Housing • Virulence • Geography • Immunogenicity • Occupational setting • Antigenic stability • Air quality • Survival • Food • Age • Sex Host • Genotype • Behaviour • Nutritional status • Health status

Epidemiologic Triad-Related Concepts Infectivity (ability to infect) (number infected / number susceptible) x 100

Epidemiologic Triad-Related Concepts Infectivity (ability to infect) (number infected / number susceptible) x 100 Pathogenicity (ability to cause disease) (number with clinical disease / number infected) x 100 Virulence (ability to cause death) (number of deaths / number with disease) x 100 All are dependent on host factors

Predisposition to Infections (Host Factors) Gender Genetics Climate and Weather Nutrition, Stress, Sleep Smoking

Predisposition to Infections (Host Factors) Gender Genetics Climate and Weather Nutrition, Stress, Sleep Smoking Stomach acidity Hygiene

Chain of Infection

Chain of Infection

Chain of Infection Horton & Parker: Informed Infection Control Practice

Chain of Infection Horton & Parker: Informed Infection Control Practice

Infection Cycle of Schistosomiasis Peters: Tropical Medicine and Parasitology, 2001

Infection Cycle of Schistosomiasis Peters: Tropical Medicine and Parasitology, 2001

Infection Cycle of Leishmaniasis Lipoldova & Demand, 2006 (www)

Infection Cycle of Leishmaniasis Lipoldova & Demand, 2006 (www)

Iceberg Concept of Infection

Iceberg Concept of Infection

Infectious Agents Bacteria Viruses Fungi Protoctists / Protozoa Helminths Algae Prions (proteinaceous infectious agents)

Infectious Agents Bacteria Viruses Fungi Protoctists / Protozoa Helminths Algae Prions (proteinaceous infectious agents)

Phylogenetic Classification of Bacteria Oxford Textbook of Medicine

Phylogenetic Classification of Bacteria Oxford Textbook of Medicine

Phylogenetic Classification of Viruses Oxford Textbook of Medicine

Phylogenetic Classification of Viruses Oxford Textbook of Medicine

Prions (PRI-ons: proteinaceous infectious agents) Mabbott & Mac. Pherson, Nat Rev Microbiol 2006 (www)

Prions (PRI-ons: proteinaceous infectious agents) Mabbott & Mac. Pherson, Nat Rev Microbiol 2006 (www)

Reservoirs A host that carries a pathogen without injury to itself and serves as

Reservoirs A host that carries a pathogen without injury to itself and serves as a source of infection for other host organisms (asymptomatic infective carriers)

Reservoirs Humans {hepatitis} Other Vertebrates {zoonoses} Birds & Bats {histoplasmosis} NOT vectors

Reservoirs Humans {hepatitis} Other Vertebrates {zoonoses} Birds & Bats {histoplasmosis} NOT vectors

Vectors A host that carries a pathogen without injury to itself and spreads the

Vectors A host that carries a pathogen without injury to itself and spreads the pathogen to susceptible organisms (asymptomatic carriers of pathogens)

Vectors Other parasites have life cycles that involve intermediate organisms, or vectors, which carry

Vectors Other parasites have life cycles that involve intermediate organisms, or vectors, which carry disease -causing microorganisms from one host to another. The protozoan blood parasite that causes sleeping sickness, or trypanosomiasis, infects humans, cattle, and other animals. It uses the tsetse fly as a vector to carry it from one host to the next. When a tsetse fly bites an infected animal, it picks up the parasite when it sucks blood. When an infected fly bites another animal, the parasite enters the bloodstream and begins to reproduce in the new host.

Arthropod Vectors Pathogen - Vector Viruses (Arbovirus) - Mosquitoes Bacteria (Yersinia) - Fleas Bacteria

Arthropod Vectors Pathogen - Vector Viruses (Arbovirus) - Mosquitoes Bacteria (Yersinia) - Fleas Bacteria (Borrelia) - Ticks Rickettsias (R. prowazeki) - Lice, ticks Protozoa (Plasmodium) - Mosquitoes Protozoa (Trypanozoma) - Tsetse flies Helminths (Onchocerca) - Simulium flies

Koch’s Postulates The same organism is present in every case It is isolated or

Koch’s Postulates The same organism is present in every case It is isolated or grown in pure culture The disease can be reproduced in healthy animals after infection with pure culture The identical pathogen is reisolated from the experimental animals

Koch’s Postulates

Koch’s Postulates

Ecological Factors in Infections Altered environment {Air conditioning} Changes in food production & handling

Ecological Factors in Infections Altered environment {Air conditioning} Changes in food production & handling {intensive husbandry with antibiotic protection; deep-freeze; fast food industry} Climate changes {Global warming} Deforestation Ownership of (exotic) pets Air travel & Exotic journeys / Global movements Increased use of immunosuppressives/ antibiotics American Museum of Natural History Exhibition: Epidemic! The World of Infectious Disease

Infectious Disease Process Direct tissue invasion Toxins Persistent or latent infection Altered susceptibility to

Infectious Disease Process Direct tissue invasion Toxins Persistent or latent infection Altered susceptibility to drugs Immune suppression Immune activation (cytokine storm)

Mathematical Modelling in Infectious Disease Epidemiology

Mathematical Modelling in Infectious Disease Epidemiology

Reproductive Number, R 0 A measure of the potential for transmission The basic reproductive

Reproductive Number, R 0 A measure of the potential for transmission The basic reproductive number, R 0, the mean number of individuals directly infected by an infectious case through the total infectious period, when introduced to a susceptible population probability of transmission per contact R 0 = p • c • d duration of infectiousness contacts per unit time Infection will …. . disappear, if become endemic, if become epidemic, if R<1 R=1 R>1

Reproductive Number, R 0 • Useful summary statistic • Definition: the average number of

Reproductive Number, R 0 • 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

Reproductive Number, R 0 • If R 0 < 1 then infection cannot invade

Reproductive Number, R 0 • If R 0 < 1 then infection cannot invade a population – implications: infection control mechanisms unnecessary (therefore not cost-effective) • If R 0 > 1 then (on average) the pathogen will invade that population – implications: control measures (social distancing, etc) necessary to prevent (delay) an epidemic

Reproductive Number, R 0

Reproductive Number, R 0

Reproductive Number, R 0

Reproductive Number, R 0

Reproductive Number, R 0

Reproductive Number, R 0

Reproductive Number, R 0

Reproductive Number, R 0

Reproductive Number, R 0 Use in STI Control R 0 = p • c

Reproductive Number, R 0 Use in STI Control R 0 = p • c • d p c condoms, acyclovir, zidovudine d case ascertainment (screening, partner notification), treatment, compliance, health seeking behaviour, accessibility of services health education, negotiating skills

Reproductive Number, R 0

Reproductive Number, R 0

What determines R 0 ? p, transmission probability per exposure – depends on the

What determines R 0 ? p, transmission probability per exposure – depends on the infection v HIV, p(hand shake)=0, p(transfusion)=1, p(sex)=0. 001 v interventions often aim at reducing p v use gloves, screene blood, condoms c, number of contacts per time unit – relevant contact depends on infection v same room, within sneezing distance, skin contact v interventions often aim at reducing c v Isolation, sexual abstinence d, duration of infectious period v may be reduced by medical interventions (TB, but not salmonella) (www)

Immunity – herd immunity v If R 0 is the mean number of secondary

Immunity – herd immunity v If R 0 is the mean number of secondary cases in a susceptible population, then R is the mean number of secondary cases in a population where a proportion, p, are immune R = R 0 – (p • R 0) v. What proportion needs to be immune to prevent epidemics? If R 0 is 2, then R < 1 if the proportion of immune, p, is > 0. 50 If R 0 is 4, then R < 1 if the proportion of immune, p, is > 0. 75 v If the mean number of secondary cases should be < 1, then R 0 – (p • R 0) < 1 p > (R 0 – 1)/R 0 = 1 – 1/R 0 v If R 0 =15, how large will p need to be to avoid an epidemic? p > 1 -1/15 = 0. 94 v The higher R 0, the higher proportion of immune required for herd immunity

Endemic - Epidemic - Pandemic Cases R>1 R=1 R<1 Time v Endemic v Transmission

Endemic - Epidemic - Pandemic Cases R>1 R=1 R<1 Time v Endemic v Transmission occur, but the number of cases remains constant v Epidemic v The number of cases increases v Pandemic v When epidemics occur at several continents – global epidemic (www)

Number of Cases of a Disease Endemic vs Epidemic Endemic Time Epidemic

Number of Cases of a Disease Endemic vs Epidemic Endemic Time Epidemic

Levels of Disease Occurrence Sporadic level: occasional cases occurring at irregular intervals Endemic level:

Levels of Disease Occurrence 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

Stages of an Outbreak: COVID-19

Stages of an Outbreak: COVID-19

Controlling Outbreaks: COVID-19 Phases of Outbreak Control: • Containment/Suppression (population-wide testing for case detection

Controlling Outbreaks: COVID-19 Phases of Outbreak Control: • Containment/Suppression (population-wide testing for case detection and case isolation (CDCI); contact tracing and quarantine of contacts (CTQ); hand washing/face masks to reduce transmission and contact rates, and ultimately to reduce the reproduction number (the average number of secondary cases each case generates)) • Delay/Slow (social distancing to flatten the epidemic curve) • Mitigation (interventions to reduce the health impact of an epidemic like more medical institutions to detect cases and treat serious patients) • Resolution

Controlling Outbreaks: COVID-19

Controlling Outbreaks: COVID-19

Controlling Outbreaks: COVID-19

Controlling Outbreaks: COVID-19

Controlling Outbreaks: COVID-19

Controlling Outbreaks: COVID-19

Controlling Outbreaks: COVID-19

Controlling Outbreaks: COVID-19

Controlling Outbreaks: COVID-19

Controlling Outbreaks: COVID-19

Controlling Outbreaks

Controlling Outbreaks

Controlling Outbreaks

Controlling Outbreaks

Controlling Outbreaks

Controlling Outbreaks

Controlling Outbreaks

Controlling Outbreaks

Additional Resource

Additional Resource

http: //www. dorak. info

http: //www. dorak. info