Transcript Principles of Infectious Disease Epidemiology [M.Tevfik DORAK]

Epidemiology of Infectious
Diseases
M. Tevfik DORAK
http://www.dorak.info
(www)
Infectious Disease Epidemiology:
Major Differences
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A case can also be an exposure
Subclinical infections influence epidemiology
Contact patterns play major role
Immunity
There is sometimes a need for urgency
(www)
What is infectious disease epidemiology?
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
(www)
What is infectious disease epidemiology?
Two or more populations
Humans
Infectious agents
Helminths, bacteria, fungi, protozoa, viruses, prions
Vectors
Mosquito (protozoa-malaria), snails (helminths-schistosomiasis)
Blackfly (microfilaria-onchocerciasis) – bacteria?
Animals
Dogs and sheep/goats – Echinococcus
Mice and ticks – Borrelia
(www)
What is infectious disease epidemiology?
A case is a risk factor …
Infection in one person can be transmitted to others
(www)
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
(www)
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 …
Infectious Disease
Definitions
 Infectious diseases
Tetanus
Measles
vCJD
 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?
(www)
Routes of transmission
Direct
Indirect
 Skin-skin
 Herpes type 1
 Mucous-mucous
 Food-borne
 STI
 Across placenta
 toxoplasmosis
 Through breast milk
 HIV
 Salmonella
 Water-borne
 Hepatitis A
 Vector-borne
 Malaria
 Air-borne
 Chickenpox
 Sneeze-cough
 Influenza
Exposure
 A relevant contact – depends on the agent
Skin, sexual intercourse, water contact, etc
(www)
(www)
Some Pathogens that Cross the Placenta
Modes of Disease Transmission
Exposure to Infectious Agents
No infection
Death
Clinical
Carrier
Sub-clinical
Immunity
Carrier
No immunity
Outcome
(www)
Timeline for Infection
Dynamics of
infectiousness
Latent
period
Infectious
period
Non-infectious
Susceptible
Time
Dynamics of
disease
Incubation
period
Symptomatic
period
Non-diseased
Susceptible
Time
(www)
Transmission
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
T
S
Susceptible
Immune
Sub-clinical
P
S
S
T
Clinical
(www)
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
(www)
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
• Virulence
• Geography
• Immunogenicity
• Occupational setting
• Antigenic stability
• Air quality
• Survival
• Food
• Age
• Sex
Host
• Genotype
• Behaviour
• Nutritional status
• Health status
(www)
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
Stomach Acidity
Hygiene
Chain of Infection
Horton & Parker: Informed Infection Control Practice
(www)
Infection Cycle of Schistosomiasis
Peters: Tropical Medicine and Parasitology, 2001 (www)
Infection Cycle of Leishmaniasis
Lipoldova & Demand, 2006 (www)
Iceberg Concept of Infection
Infectious Agents
Bacteria
Viruses
Fungi
Protoctists / Protozoa
Helminths
Algae
Prions
(proteinaceous infectious agents)
Phylogenetic Classification of Bacteria
Oxford Textbook of Medicine
Phylogenetic Classification of Viruses
Oxford Textbook of Medicine
Prions
(PRI-ons: proteinaceous infectious agents)
Mabbott & MacPherson, Nat Rev Microbiol 2006 (www)
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)
(www)
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
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
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
Ecological Factors in Infections
Altered environment
{Air conditioning}
Changes in food production & handling
{intensive husbandry with antibiotic protection; deepfreeze; 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
Reproductive Number, R0
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
probability of transmission per contact
R0 = 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
(www)
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
(www)
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, R0
Use in STI Control
R0 = 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
(www)
What determines R0 ?
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)
(www)
Immunity – herd immunity
If R0 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 = 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 > 0.50
If 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
R>1
R=1
R<1
Time
 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
(www)
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: 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
(www)
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