Epidemiology of Infectious Diseases M. Tevfik DORAK (www)www.

Epidemiology of Infectious Epidemiology of Infectious DiseasesDiseases

M. Tevfik DORAKhttp://www.dorak.info

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Infectious Disease Epidemiology: Major Differences

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

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Epidemiology• Deals with one population• Risk case• Identifies causes

Infectious disease epidemiology Two or more populations A case is a risk factor The cause often known

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What is infectious disease epidemiology?

Two or more populationsHumansInfectious agents

Helminths, bacteria, fungi, protozoa, viruses, prions

Vectors Mosquito (protozoa-malaria), snails (helminths-schistosomiasis)Blackfly (microfilaria-onchocerciasis) – bacteria?

AnimalsDogs and sheep/goats – EchinococcusMice and ticks – Borrelia

What is infectious disease epidemiology?

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A case is a risk factor …Infection in one person can be transmitted to others

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What is infectious disease epidemiology?

The cause often known An infectious agent is a necessary cause

What is infectious disease epidemiology used for? Identification of causes of new, emerging infections, e.g. HIV, vCJD, SARS Surveillence of infectious disease Identification of source of outbreaks Studies of routes of transmission and natural history of infections Identification of new interventions

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What is infectious disease epidemiology?

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, clone, resistance, repeat episodes …

Definitions Infectious diseases

Caused by an infectious agent Communicable diseases

Transmission – directly or indirectly – from an infected person Transmissible diseases

Transmission – through unnatural routes – from an infected person

Note Infections are often subclinical – infections vs infectious diseases! Antonyms not well-defined

Non-communicable diseases – virus involved in pathogenesis of diabetes? Chronic diseases – HIV?

TetanusTetanus MeaslesMeasles vCJDvCJD

Infectious Disease

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Routes of transmission

Direct Skin-skin

Herpes type 1 Mucous-mucous

STI Across placenta

toxoplasmosis Through breast milk

HIV Sneeze-cough

Influenza

Indirect Food-borne

Salmonella Water-borne

Hepatitis A Vector-borne

Malaria Air-borne

Chickenpox

Exposure A relevant contact – depends on the agent

Skin, sexual intercourse, water contact, etc

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Some Pathogens that Cross the Placenta

Modes of Disease Transmission

No infection Clinical Sub-clinical Carrier

Death Carrier Immunity No immunity

Outcome

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Exposure to Infectious Agents

Infe

ctio

nSusceptible

Susceptible

Dynamics of infectiousness

Dynamics of disease

Incubation period

Symptomaticperiod

Non-diseased

Latentperiod

Infectious period

Non-infectious

Infe

ctio

n

Time

Time

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Timeline for Infection

Cases Index – the first case identified Primary – the case that brings the infection into a population Secondary – infected by a primary case Tertiary – infected by a secondary case

P

S

S

T

Susceptible

Immune

Sub-clinical

Clinical

ST

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Transmission

Data from Dr. Simpson’s studies in England (1952)

Measles Chickenpox Rubella

Children exposed

Children ill

attack rate

251

201

0.80

238

172

0.72

218

82

0.38

Attack rate = illexposed

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Person-to-Person Transmission

Disease is the result of forces within a dynamic system consisting of:agent of infection

hostenvironment

Epidemiologic Triad

Agent

Host

Environment

• Age

• Sex

• Genotype

• Behaviour

• Nutritional status

• Health status

• Infectivity

• Pathogenicity

• Virulence

• Immunogenicity

• Antigenic stability

• Survival

• Weather

• Housing

• Geography

• Occupational setting

• Air quality

• Food

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Factors Influencing Disease Transmission

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

Epidemiologic Triad-Related Concepts

Predisposition to Infections(Host Factors)

Gender

Genetics

Climate and Weather

Nutrition, Stress, Sleep

Smoking

Stomach Acidity

Hygiene

Horton & Parker: Informed Infection Control Practice (www)

Chain of Infection

Peters: Tropical Medicine and Parasitology, 2001 (www)

Infection Cycle of Schistosomiasis

Lipoldova & Demand, 2006 (www)

Infection Cycle of Leishmaniasis

Iceberg Concept of Infection

Bacteria

Viruses

Fungi

Protoctists / Protozoa

Helminths

Algae

Prions(proteinaceous infectious agents)

Infectious Agents

Phylogenetic Classification of Bacteria

Oxford Textbook of Medicine

Phylogenetic Classification of Viruses

Oxford Textbook of Medicine

Mabbott & MacPherson, Nat Rev Microbiol 2006 (www)

Prions(PRI-ons: proteinaceous infectious agents)

A host that carries a pathogen without injury to itself and serves as a source of infection for other

host organisms

(asymptomatic infective carriers)(www)

Reservoirs

Humans{hepatitis}

Other Vertebrates{zoonoses}

Birds & Bats{histoplasmosis}

NOT vectors

Reservoirs

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 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 (Borrelia) - Ticks

Rickettsias (R. prowazeki) - Lice, ticks

Protozoa (Plasmodium) - Mosquitoes

Protozoa (Trypanozoma) -Tsetse flies

Helminths (Onchocerca) - Simulium flies

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{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 (www)

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

A measure of the potential for transmission

The basic reproductive number, R0, the mean number of individuals directly infected by an infectious case through the total infectious period, when introduced to a susceptible population

R0 = p • c • d

contacts per unit time

probability of transmission per contact

duration of infectiousness

Infection will ….. disappear, if R < 1become endemic, if R = 1become epidemic, if R > 1

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Reproductive Number, Reproductive 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

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Reproductive Number, Reproductive Number, R0

• 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

Reproductive Number, Reproductive Number, R0

p condoms, acyclovir, zidovudine

c health education, negotiating skills

D case ascertainment (screening,partner notification), treatment, compliance, health seeking

behaviour, accessibility of services

R0 = p • c • d

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Reproductive Number, Reproductive Number, R0

Use in STI Control

p, transmission probability per exposure – depends on the infection HIV, p(hand shake)=0, p(transfusion)=1, p(sex)=0.001 interventions often aim at reducing p

use gloves, screene blood, condoms

c, number of contacts per time unit – relevant contact depends on infection same room, within sneezing distance, skin contact, interventions often aim at reducing c

Isolation, sexual abstinence

d, duration of infectious period may be reduced by medical interventions (TB, but not salmonella)

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What determines What determines R0 ?

Immunity – herd immunity

If R0 is the mean number of secondary cases in a susceptible population, thenR is the mean number of secondary cases in a population where a proportion, p, are immune

R = R0 – (p • R0)

What proportion needs to be immune to prevent epidemics?If R0 is 2, then R < 1 if the proportion of immune, p, is > 0.50If R0 is 4, then R < 1 if the proportion of immune, p, is > 0.75

If the mean number of secondary cases should be < 1, then R0 – (p • R0) < 1

p > (R0 – 1)/ R0 = 1 – 1/ R0

If R0 =15, how large will p need to be to avoid an epidemic?

p > 1-1/15 = 0.94

The higher R0, the higher proportion of immune required for herd immunity(www)

Endemic - Epidemic - Pandemic

Endemic Transmission occur, but the number of cases remains

constant Epidemic

The number of cases increases Pandemic

When epidemics occur at several continents – global epidemic

Time

Ca

ses

R = 1

R > 1

R < 1

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Endemic EpidemicNu

mb

er o

f C

ases

of

a D

isea

se

Time

Endemic vs Epidemic

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 occurrenceEpidemic or outbreak: occurrence clearly in excess of the expected level for a given time periodPandemic: epidemic spread over several countries or continents, affecting a large number of people

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