Association and Causation (2)

8/6/2019 Association and Causation (2)

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By Kshitij Chaurasia


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` Definitions.

` History.

` Concepts of causation.

` Defining the variable in an association.

` Types of Association.` Spurious association.

` Indirect association.

` Direct association.

` Additional criteria for judging causality.

` Measuring an association.

` Problems in establishing causality.

` Establishing a causal inference.

` References.


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Defining an association

` Concurrence of two variables (A and B) more oftenthan would be expected by chance.

` An association is present if probability of occurrence

of a variable depends upon one or more variable.

(A dictionary of Epidemiology by John

M. Last)


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Synonyms: correlation, statistical dependence,relationship

An association is said to be causal when it canbe proved that change in the independentvariable produces change in the dependent

variable. BA

EXPOSURE diseases


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` An exercise in measurement of an effect rather

than as a criterion-guided process for deciding

whether an effect is present or not.

Am J Public Health. 2005;95:S144S150


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If one of these attributes say A is the suspected cause

and the other say B is a disease then we have a reason

to suspect that A has caused B.

Karl Popper stressed thatscience progresses by

rejecting or modifying causal hypotheses, not by

actually proving causation.


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` 1835- Pierre-Charles-Alexandre Louis The

"Father of Medical Statistics a clinician,

selected 77 patients of homogeneous group

with the same, well-characterized form of

pneumonia for his bloodletting analysis.


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` John Snow (15 March 1813 16

June 1858) a British physician and a

leader in the adoption

of anaesthesia and medicalhygiene.

` He is considered to be one of the

fathers of epidemiology, because of

his work in tracing the source ofa cholera outbreak in Soho, England,

in 1854.


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` Up to the time of Louis Pasteur (1895-1922)

various concept of disease causation were in

vogue, e.g.,

` Supernatural theory of disease,` The theory of humors,

` The concept of contagion,

` Miasmatic theory of disease

` The theory of spontaneous regeneration


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` The concept gained momentum during the 19th

and early part of20th century.

` Emphasized one-to-one relationship between

causal agent and disease.

Disease agent Man Disease


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` Susceptible host (the person

at risk for the disease),

` Disease agent (the proximatecause)

` Environmental context for

interaction between host andagent


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` Pettenkofer of Munich (1819-1901) was an early

proponent of this concept.

` Germ theory of disease overshadowed themultiple cause theory.

` Example: Tuberculosis is caused not merely due

to tubercle bacilli, factors such as poverty,overcrowding and malnutrition also contribute.


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` In seeking a model that better expressed thecomplex reality of multicausality, some

epidemiologists began thinking in terms of chains

of causation.

` Example- "diet-heart hypothesis" (DHH) as

described by Sherwin (1978).


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` A diet high in saturated fat and cholesterol leads to

high blood lipids, which lead to atherosclerosis

(coronary artery disease), which leads to coronary

heart disease and the clinical event of amyocardial infarct (heart attack).

` It was over simplified model.


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` Suggested by MacMohon, Pugh and Ipsen (1960)

` Model is suited in the study of chronic disease,

where disease agent is often unknown butdepends on multiple factors.

` Considers all predisposing factors and their

complex interrelationship.


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` De-emphasizes

the agent as the

sole cause of

disease,` Emphasizing the

interplay of

physical,

biological andsocial

environments


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` Example: Potatoe famine ofIreland in mid 19th

century

Fungal invasion of potato crops

Predominantly peasant population subsistingon a potato diet

Repressive British colonial rule.


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` Commonly used paradigm

in the injury prevention field.


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` Causal relationships are used to make public

health decisions and design interventions.

` In example, if smoking was indeed causal, itwould be irresponsible to target coffee

drinking as an intervention.


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` Independent variable: The variable which changesirrespective of dependent variable.

` Dependent variable: The variable which changesaccording to dependent variable.


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` Independent and dependent variable depends on the study

hypothesis variable involved in hypertension

Hypertension CHD Independent

Salt intake Hypertension Dependent

Hypertension

causes

Obesity CHD Confounder


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` Intermediate or intervening variables :

causes causes

Salt intake hypertension CHD

` Social condition or Development ( causal variable )access to prenatal care, better nutrition, vaccination,better personal hygiene.


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` Some independent variables may modify the effect of

the hypothesized casual variable.

black

` Hypertension CHD

` Some confounding variables are also effect modifiers.


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` It can be grouped under three headings

i. Spurious association.

ii. Indirect association.

iii. Direct (causal) association.

` On the basis of causality

i.

Causalii. Non causal

` Positive and Negative


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This is an association which appears due to impropercomparison.

Observed association between a disease andsuspected factor may not be real.


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` Example: In an study in UK neonatal mortality was observed to be

more in the newborns born in a hospital than those born athome. This is likely to lead to a conclusion that homedelivery is better for the health of newborn.

However, this conclusion was not drawn in the studybecause the proportion of high risk deliveries was foundto be higher in the hospital than in home.


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` Statistical association between a characteristic of interest

and a disease due to the presence of another factor,

known or unknown.

A (Altitude)

C

(Iodine B (Endemic goitre)Deficiency)


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1. One-to-one causal association:

` Two variables are stated to be causally related

(AB) if change in A is followed by a change in B.

` When the disease is present, the factor mustalso be present.

A(Bacteria) B (Disease)


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`

Example: Koch's postulates

The microorganism must be found in abundance in all

organisms suffering from the disease, but should not be

found in healthy animals.

The microorganism must be isolated from a diseased

organism and grown in pure culture.


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The cultured microorganism should cause disease when

introduced into a healthy organism.

The microorganism must be reisolated from the

inoculated, diseased experimental host and identified as

being identical to the original specific causative agent.


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2. Multifactorial causation:

Multiple factors are involved in causingthe disease, ex. CHD.


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` If E is the exposure factor & D is the disease

E1

E2

D Independently causalE3

E1

D Conditionally causalE2


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E1

+ D Synergism

E2

E2 Effect modification

E1 D ( or form of synergism)

E2

E1 D Confounding

association of E1 and D.


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` One cause with multiple effects

D1 Leukemia

E D2 Lung CancerRadiation D3Radiation sickness


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` In absence of controlled experimental evidence to

incriminate the cause other criteria to decide

causal association:

1. Temporal Association.

2. Strength of association.

3. Specificity of the association.

4. Consistency of the association.5. Biological plausibility.

6. Coherence of the association.


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Hillscriteria

Strength

Consistency

Specificity

Temporality

Biologicalgradient

Plausibility

Coherence

Experimental

evidence

Analogy

24-Dec-08 38DEPT. OF COMMUNITY MEDICINE,

UCMS&GTBH DELHI.


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The causal attribute must precede the disease or unfavorable

outcome.

Exposure to the factor must have occurred before the disease

developed.

Length of interval between exposure and disease very

important

If the disease develops in a period of time too soon after

exposure, the causal relationship is called into question.


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Asbestos Latent periodof 10 - 20 yrs

Lung Cancer

AsbestosLatentperiodof 3 yrs

Lung Cancer

In this case, the latent period is not long enough for lung cancer todevelop if caused by exposure.

Well - established temporalrelationship

Asbetos and Lung Cancer

New Study


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Relationship between cause and outcome could be strong orweak.

There are statistical methods to quantify the strength ofassociation viz; calculation of relative risk, attributable risketc.


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(Incidence Rate)

(RR = IRE/IRU)


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` Rate in exposed (E)

` Rate in unexposed (U)

` Attributable fraction:

` Odds ratio*:A/C

B/D

E - U

E

* Used in case-control studies


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` The larger the relative risk or odds ratio, thehigher the likelihood that the relationship iscausal.

` However, care must be taken to examineconfidence intervals and sample size. For example, if the confidence interval is wide (e.g.,

1.8 - 22.6), an OR of 12.0 is less strong because we

are less confident of the strength of the odds ratio.


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Consistency is the occurrence of the association at some othertime and place repeatedly.

If a relationship is causal, the findings should be consistentwith other data.

If there is no consistency it will weaken a causalinterpretation.

Example:The causal association between smoking and lung cancer

due to its consistency.


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The weakest of the criteria (should probably be eliminated)

Specific exposure is associated with only one disease.

This is used by tobacco companies to argue that smoking isnot causal in lung cancer. Smoking is associated with many diseases.

Specificity implies a one to one relationship between the cause

and effect.


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Causal significance of an association is its unity with

known facts that are thought to be related.

E.g.: the rising consumption of tobacco in the form ofcigarettes and the rising incidence of lung cancer are

coherent.


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The association must be consistent with the otherknowledge (viz mechanism of action, evidence fromanimal experiments etc).

Sometimes the lack of plausibility may simply be dueto the lack of sufficient knowledge about thepathogenesis of a disease.


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` With increasing dose, there is increasing risk of disease.

` This is not considered necessary for a causal

relationship, but does provide additional evidence that a

causal relationship exists.

` With increasing level of exposure to the risk factor an

increase in incidence of the disease is found.


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Age-standardized death rates due to well-established cases of bronchogenic carcinoma


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` If there is a true causal relationship betweenexposure and disease, the expectation is thatwe would see the association consistently in

other (NOT

necessarily all) subgroups of thepopulation.


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` Upon elimination or reduction of exposure to the factor,the risk of disease declines.

` Strengthen the association being causal.

` Example: diminishing of leukoplakia lesion on cessationof tobacco chewing.

` HOWEVER, in certain cases, the damage may be

irreversible.

` Example: Emphysema is not reversed with the cessationof smoking, but its progression is reduced.


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OBSERVED

ASSOCIATION

DUE TO

BIAS

DUE TO

CONFOUNDIN

G

DUE TO

CHANCE

COULD IT

BE

CAUSAL

NO

NO

NO

PROBABLY

NO


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` Bias is systematic favoritism (error) that is present

in the data collection process resulting in misleading

results.

` Reasons: No control over participants in studies

To not obtain representative sample of population under

study

Difficulty to measure variables


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` Types of bias: Selection bias: When there is a systematic difference

between the characteristics of people selected for a study

and those who are not.

x Example: In a study for assessing tobacco habit people who

responded were not having tobacco habit where as people

who not responded were having.


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` Measurement Bias: When measurement or

classifications of disease or exposure rate

inaccurate.

Example: Biochemical or physiological measurements are

never completely accurate.


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` When another exposure exists in the study

population associated with both disease and

exposure being studied. Example:

Exposure Disease

(coffee drinking) (Heart Disease)

Confounding factor

(Cigarette smoking)


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Second step in determining causation: ConductingStudies in Human Populations

Human Epidemiology.

All of the study designs are important here andprovide different evidence for or against acausal hypothesis.


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Clinical observations

Available data(Ecological or Cross-sectional Studies)

Case-control studies

Cohort studies

Randomized trials(only used for potentially beneficial treatments)


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` Nature of Causation Token causal claims

Type causal claims

` Types of Causal relationships Direct

Indirect

` Types of causal factors Sufficient

Necessary


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`

Claims about causation between particular tokens,not populations

Event A caused event B

Tobacco caused cancer

Having property A caused X to have property B

Smoking caused high temperature on palate to

cause smokers palate


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- Thing 1 having property A caused Thing 2 to have

property B

Sugar diet caused caries in caries prone

individual.


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`

About causation that occurs in general, or in thepopulation

Events of type A cause events of type B

Tobacco habit causes high prevalance of lungcancer

Having property A causes things of type X to

have property BSome smokers get smokers palate because they

smoke


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- Thing 1 having property A caused Thing 2 to have

property B

Caries prone individuals have high caries rate

who are on sugar diet.


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Factor Factor 1

Disease

Factor 2

Factor 3

Factor 4

Disease

Direct Indirect


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(F508 Polymorphism High cholesterol

Cystic Fibrosis

Artery thickening

Hemostatic factors

Myocardial infarction

Direct Indirect


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` Predisposing factors: such as age, sex, previousillness etc.

` Enabling factors: such as low income, poor

nutrition, bad housing etc

` Precipitating factors: such as exposure to a

specific disease agent of noxious agent.

` Reinforcing factors: such as repeated exposure


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` Necessary and sufficient Without factor, disease does not develop Example: HIV

` Necessary but not sufficient Multiple factors, including main factor, required Example: Development of tuberculosis requires M.

tuberculosis and other factors, such asimmunosuppression, to cause disease

Bacteria still necessary, but not sufficient to causethe disease


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` The existence of a correlation or association does notnecessarily imply causation.

` The concept of single cause, once held in relation tocommunicable disease, has been replaced by conceptof multiple causation in disease.

` The criteria used in establishing causality in infectiousdisease are not applicable to non infectious diseases,KOCHS Postulates.(not totally applicable in some

infectious diseases.)

` Relatively long period between exposure & clinicalappearance of a disease..


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` Certain factors or confounders tend to distort the

relationship with suspected factors

` Spurious associations between a disease &

suspected factors.


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` Association is symmetric

` Causation is asymmetric

` Example

` Xassociated with Y Y associated with X` Xcauses Y Y causes X

` In fact, for token-causation, we think we have:

` Xcauses Y Y does not cause X


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` Although different, they are connected

In general,

IfXcauses Y, then Xwill be associated with Y

IfXand Y are associated, then there is some sortof causal connection between them

` Statistics is relevant to science precisely because

the two are connected

` Causal inference is really the problem of movingbetween these two types of claims


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` Statistical association established

` Selection and information bias excluded.

` Confounding excluded or neutralized &association persists.

` Confirmatory criteria of causality (strength,biological factor, consistent, experimental proof.)

CAUSAL INFERENCE


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` Parks text book of Preventive and Social Medicine, K.Park.

` Biostatistics by Mahajan

` Basic epidemiology by Beaglehole

` http://duncansepidemiology.tripod.com/id9.html

` http://www.slideshare.net/akhileshbhargava/causal-

association?from=share_email` http://www.slideshare.net/gane_spm/measues-of-association

` http://www.slideshare.net/guestc43c63/association-and-causation-

presentation

` http://www.slideshare.net/akhileshbhargava/causal-association

`

http://www.jerrydallal.com/LHSP/cause.htm


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` http://en.wikipedia.org/wiki/Koch's_postulates

` http://en.wikipedia.org/wiki/John_Snow_(physician)

` http://books.google.co.in/books?id=wnGU_TsW3BQC&pg=PA310&lpg=PA3

10&dq=causal+claims+type+and+token&source=bl&ots=7bXF4DL1LU&sig

=DGIYRyI5WrTzSqIaScALVcgZYd0&hl=en&ei=Dv5DTNO5DMGFrQfSpNX

aDQ&sa=X&oi=book_result&ct=result&resnum=1&ved=

0CBUQ

6AEwAA#v=onepage&q=causal%20claims%20type%20and%20token&f=false


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THANK YOU


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` 1. To study historically the rise and fall of

disease in the population.

` 2. Community diagnosis.

` 3. Planning and evaluation.

` 4. Evaluation of individuals risk chances.

` 5. Syndrome identification.

` 6. Completing the natural history of disease.

` 7. Searching for causes and risk factors.


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` Communicable diseases are transmitted from

the reservoir or source of infection to susceptible

host.

Susceptible Host

Source orReservoir Modes of Transmission


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` The source of infection isdefine as the person, animal,object or substance fromwhich an infectious agentpasses or is disseminated tothe host.

`

A reservoir is define as anyperson, animal, arthropod,plant, soil or substance orcombination of these in whichinfectious agent lives andmultiplies

` Reservoir is natural habitants

in which the organismmetabolizes and replicates.


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` Reservoir and Source are not always synonyms.

` For example, hookworm infection, In tetanus,

` Reservoir a) homologous reservoir.

b) heterologous reservoir.` The reservoir may be of three types:

a) Human reservoir.

b) Animal reservoir.

c) Reservoir in non living things.


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a) Cases : A person in a population or study groupidentified as having the particular disease.

Presence of infection in a host :

a) Clinical illnessmild, moderate, severe, fatal,

b) Subclinical. - dominant role in spread ofinfection.

c)Latent infection.- the host does not shed theinfectious agent which liesdormant within the host

without symptoms.eg: Herpes simplex


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B) CARRIERS : an infected person or animal that harbors

a specific infectious agent in the absence of discernible

clinical disease and serves as a potential source of

infection for others.

Carriers may be classified as :A) Type :a) Incubatory who shed the infectious agent

during the incubation period of the disease.

eg.measles,mumps polio,hepatitis


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b) convalescent carriers : continue to shed thedisease agent during the period of convalescent, e.g.

typhoid fever.

c) healthy carriers : they are victim of subclinical

infection who have developed carrier state withoutsuffering from the disease. e.g. cholera, diphtheria, polio.

B) Duration

a) Temporary

b) chronicC) By portal of exit: urinary carrier, respiratory, nasal.


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` The source of infection may sometimes be animals and

birds. These, like human sources of infection, may cases

or carriers.

` Zoonoses The diseases and infections which are

transmitted to man from vertebrates.` E.g. are rabies, yellow fever, influenza.

` There is evidence that genetic recombination between

animal and human virus might produce new strain of

viruses e.g. influenza viruses.


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` Soil and inanimate matter can

also act as reservoirs of

infections. For example, soil

may harbour agent that cause

tetanus, anthrax, mycetoma.


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B) INDIRECTTRANSMISSION

a) Vehicle born

b) Vector born -- mechanical

-- biological

c) Air born ---Droplet nuclei

-- Dust

d) Fomite born

e) Unclear hands and fingers


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` For the successful parasitism :1. Infectious agent must find a portal of entry by which it

may enter the host e.g. respiratory tract, alimentary tractetc.

2. On gaining entry into the host the organisms must reachthe appropriate tissue for its multiplication and survival

3. The disease agent must find a way out of the bodyinorder to reach a new host.

4. After leaving the human body the organism must survive

in the external environment for a sufficient period till anew host is found. This is called successful parasitism.


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` Definition:

` The incubation period

is the amount of time

between infection

with a virus or

bacteria to the start of

symptoms.


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` Rocky Mountain spotted fever - 2-14 days` Smallpox - 12 days` Common cold - 2-5 days

` Measles - 8-12 days` Chicken pox - 14-16 days` Erythema infectiosum (Fifth Disease) - 13-18

days` Roseola - 9-10 days` Rubella (German measles) - 14-21 days` Influenza - 1-2 days


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` Generation Time

` Communicable period

` Secondary attack rate


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` Claims about causation between particular

tokens, not populations

Event A caused event B

This light switch flip caused the lights to turn on

Having property A caused X to have property BThe glass broke because it was brittle

Thing 1 having property A caused Thing 2 to have

property B

I went to comfort my daughter because she wascrying.


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` About causation that occurs in general, or in the

population

Events of type A cause events of type B

Light switches turn on lights

Having property A causes things of type X tohave property B

Some glasses break because they are brittle

Thing 1 having property A caused Thing 2 to

have property BParents frequently go to comfort their children

when the children cry.


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HISTORY


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NATURE OF CAUSATION

Token causal claims Type causal claims


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When the incidence of a condition in a group with certaincharacteristic differs from the incidence in a group without

the characteristics , an association is inferred that may or

may not be causal.

The strength of the association is commonly measured bythe relative risk or odd ratio.

The relationship can also be expressed in terms of a

correlation coefficient , which is a measure of a degree to

which a dependent variable varies with an independentvariable.

Exposure


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ExposureOR

Genetic Background

ORCombination of Both

Disease or Other Outcome

? Causation ?

Association

Suppose we determine that an exposure is associated with disease.How do we know if the observed association reflects a causalrelationship?

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Association and Causation (2)

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