NATURAL HISTORY OF

DISEASE

Contents
Introduction
Models of disease causation
Factors of disease causation
Natural history of disease in man
Levels of prevention
Quantifying prognosis

Definition
Natural history of disease refers to the progress of a

disease process in an individual over time, in the

absence of intervention.
The process begins with exposure to or accumulation
of factors capable of causing disease.
Without medical intervention, the process ends with
recovery ,
disability,
or death.

Natural History of Disease

recovery
Exposure

host

disease

disability
death

Natural History of Disease

Knowledge of the natural history of disease ranks alongside
causal understanding in importance for disease prevention and
control.
Natural history of disease is one of the major elements of
descriptive epidemiology.

Natural History of Disease

The natural history of disease is best established by cohort
studies.

As these studies are costly and laborious, understanding of

the natural history of disease is largely based on other
epidemiological

studies,

such

as

cross-sectional

and

retrospective studies, undertaken in different population

settings.

Natural History of Disease

What the physician sees in the hospital is just an "episode" in
the natural history of disease.
The epidemiologist, by studying the natural history of disease
in the community setting is in a unique position to fill the gaps
in the knowledge about the natural history of disease.

Natural History of Disease

The natural history and spectrum of disease presents
challenges to the clinician and to the public health worker.

Because of the clinical spectrum, cases of illness diagnosed

by clinicians in the community often represent only the tip of
the iceberg. Many additional cases may be too early to
diagnose or may remain asymptomatic.

For the public health worker, the challenge is that persons with
undiagnosed infections may nevertheless be able to transmit
them to others.

ICEBERG CONCEPT OF DISEASE

CLINIC
AL
DISEAS
E
SUBCLINI
CAL
DISEASE

DE
AT
H

SEVERE
DISEASE
MILD ILLNESS

INFECTION WITHOUT
CLINICAL ILLNESS

EXPOSURE WITHOUT INFECTION

Models of disease
causation

Models of disease
causation
Germ theory of disease
Epidemiological Triad
Epidemiological Tetrad
BEINGS theory
Web of Causation theory
Wheel theory

Germ Theory of Disease

Proposed by Robert Koch and Louis Pasteur.
Every human disease is caused by a microbe or germ, which is
specific for that disease and one must be able to isolate the
microbe from the diseased human being.

ROBERT KOCH

LOUIS PASTEUR

Epidemiological Triad

Epidemiological Triad

Agent
Is an element or substance, animate or inanimate, the presence
(or absence) of which may initiate or perpetuate a disease
process.
A disease may have a single agent, a number of independent
alternative agents or complex of two or more factors whose
combined presence is essential for the development of the
disease.

Agent
Classification of agents:
Biological
Nutrient
Physical
Chemical
Mechanical
Absence or insufficiency or excess of a factor necessary to
health
Social

Agent characteristics
Infectivity refers to the proportion of exposed persons who
become infected.
Pathogenicity refers to the proportion of infected persons who
develop clinical disease.
Virulence refers to the proportion of persons with clinical
disease who become severely ill or die.

Agent characteristics
Hepatitis A virus in children has low pathogenicity and low virulence,
since many infected children remain asymptomatic and few develop
severe illness.
In persons with good nutrition and health, measles virus has high
pathogenicity but low virulence, since almost all infected persons
develop the characteristic rash and illness but few develop the lifethreatening presentations of measles (pneumonia, encephalitis).

In persons with poor nutrition and health, measles is a more virulent

disease, with mortality as high as 5-10%.

Rabies virus is both highly pathogenic and virulent, since virtually

100% of all infected persons (who do not receive treatment) progress
to clinical disease and death.

Host
In epidemiological terminology, the human host is referred to
as soil and the disease agent as seed.
A person or other living animal, that affords subsistence or
lodgment to an infectious agent under natural condition.
Host factors: Intrinsic factors that influence an individuals
exposure, susceptibility, or response to a causative agent.

Environment
Physical environment
Non living things and physical factors(air, water, soil,

housing, heat, light, etc)

Biological environment
Microbial agents, insects, animals, plants and man himself.
Psychosocial environment
Lifestyle, poverty, urbanization, community life, income,

education, stress etc.

HOST
FACTORS

AGENT

1.Decreased
immunity
2.Malnutrition
3.Elderly
4.HIV infection

M. Tuberculosis

ENVIRONMENT
FACTORS
1.Poor housing
2.Overcrowding
3.Poverty
4.Urbanization

Epidemiological Tetrad
Agent
Host
Environment
Time

Disease Occurrence

Different diseases, in different communities, show different

patterns of expected occurrence:

Endemic: habitual presence of a disease within a given

geographic area.

Hyperendemic :a persistently high level of occurrence.

Sporadic : an irregular pattern of occurrence, with

occasional cases occurring at irregular intervals.(prevalence
is zero)

Disease Occurrence
Epidemic: occurrence in a community or region of a group of
illnesses of similar nature, clearly in excess of normal
expectancy and derived from a common or from a propagated
source.
Public health officials often use the term outbreak, which
means the same, because it is less provocative to the public.
When an epidemic spreads over several countries or
continents, affecting a large number of people, it is called a
pandemic(worldwide epidemic).

The BEINGS Model of Disease

Causation
This concept postulates that human disease and its consequences are caused by a

complex interplay of nine different factors

Biological factors innate in a human being,
Behavioural factors concerned with individual lifestyles,
Environmental factors as physical, chemical and biological aspects of
environment,
Immunological factors,
Nutritional factors,
Genetic factors,
Social factors,
Spiritual factors and
Services factors, related to the various aspects of health care services.

The Theory of Web of

Causation
The epidemiological triad theory was very effectively used
by Leavel and Clark in explaining the natural history of
disease and levels of prevention for obviating such departures
from the state of health.
But it could not explain the causation of non communicable
diseases like IHD or road accidents.

Web of causation
McMahon and Pugh forwarded the theory of epidemiological
web of causation, wherein the various factors (e.g.
hypercholesterolemia, smoking, hypertension) are like an
interacting web of a spider.

Each factor has its own relative importance in causing the

final departure from the state of health, as well as interacts
with others, modifying the effect of each other.

Web of Causation applied to Myocardial Infarction

Example of Web of Causation

Overcrowding

Malnutrition
Exposure to
Mycobacterium

Susceptible Host

Infection

Tuberculosi
s
Tissue Invasion
and Reaction

Vaccination

Genetic

Application of the Web

Epidemiologic Triad
devised to enhance search for
understanding communicable disease

Web of Causation
devised to address non-communicable
diseases can also be applied to
communicable disease

Wheel theory
As medical knowledge advanced, an additional aspect of
interest that came into play is the comparative role of
genetic and the environmental (i.e. extrinsic factors
outside the host) factors in causation of disease.

The triad as well as the web theory does not adequately

cover up this differential.

To explain such relative contribution of genetic and

environmental factors, the wheel theory has been postulated.

Wheel theory
The theory visualizes human disease in the form of a wheel, which
has a central hub representing the genetic components and the
peripheral portion representing the environmental component.

Like any wheel, the outer part (environmental component) has

spokes (3 in this model) and the environmental component is thus
divided into 3 sub components, representing the social, biological and
physical components of the environment.

Wheel Theory

Wheel Theory

Factors of disease
causation

Factors of Disease Causation

a) Predisposing factors are factors which create a state of susceptibility, so

that the host becomes vulnerable to the agent or to necessary cause, e.g.
age, sex, previous illness.

b) Enabling factors are those which assist in the development of (or in

recovery from) the disease; e.g. housing conditions, socio-economic status.

c) Precipitating factors are those which are associated with immediate

exposure to the disease agent or onset of disease, e.g. drinking
contaminated water, close contact with a case of pulmonary TB.

Factors of Disease Causation

d) Reinforcing factors are those which aggravate an already existing
disease, e.g. malnutrition, repeated exposures
e) Risk factors : A risk factor is defined as a condition, quality or
attribute, the presence of which increases the chances of an individual
to have, develop or be adversely affected by a disease process. A risk
factor is not necessarily the cause of a disease but does increase the
probability that a person exposed to the factor may get the disease.

Exposure to
TB

No infection(70-90%)

Latent TB (90% well)

-Never develop TB
-Not infectious

Infection(10-30%)

Active TB(10% ill)

-5% develop TB within 2 years
-5% develop TB many years later

Untreated
50% die within 5 years
25% remain sick
25% recover

Treated

Cured

The Natural history of

disease in man

The Natural history of disease in a

patient
Preclinical Phase

(A)

(P)

Clinical Phase

(S)

(M)

(D)

A ; Biologic onset of disease

P ; Pathologic evidence of disease if Sought
S ; Signs and symptoms of disease
M ; Medical care sought
D ; Diagnosis
T ; Treatment
Gordis L. Epidemiology. WB Saunders Company. 1996

(T)

Primordial prevention
Prevention of the emergence or development of risk factors.
Particularly useful for chronic diseases.
Example :Many adult health problems (e.g., obesity,
hypertension) have their early origins in childhood, because
this is the time when lifestyles are formed (smoking, eating
patterns, physical exercise).
Efforts are directed towards discouraging children from
adopting harmful lifestyles .
The main intervention is through individual and mass
education.

Primary prevention
Measures of prevention undertaken during the phase of prepathogenesis (phase of susceptibility)
Involves two sub-steps: Health promotion and specific protection
Health Promotion : Steps undertaken to improve the level of
general health and well being so that conditions for initiation of
disease process are prevented.
These steps are not specific for any disease or a group of diseases.

Primary prevention
It includes
improvement in the overall socio-economic status of the
population,
health education,
feeding programmes for mothers and children,
promotion of breast feeding,
promotion of small family norms,
education
motivation for healthy lifestyle.

Primary prevention
Specific Protection : include measures to prevent the initiation of

specific diseases or a group of diseases.

Examples
Immunization to protect against specific diseases
Fortification of foods with specific nutrients (as salt with

iodine)
Use of condoms to protect against sexually transmitted

diseases (STDs)
Use of helmets to protect against head injuries

Primary prevention
Both health promotion and specific protection are type of
primary preventive strategy.
However, health promotional approach improves the general
health so that a number of diseases are aimed at.
For example, by promoting breast feeding among children, we
try to prevent general malnutrition, vitamin A deficiency,
providing antibodies against various diseases, preventing
diarrhoeal diseases.
On the other hand when condom is used, it is for a very
specific group of diseases i.e. STDs; when measles vaccine is
given it is for a specific disease viz. measles.

Primary prevention
Two types of strategy:
Population strategy
High risk strategy

Primary prevention
Population strategy

High risk strategy

Advantages:
Radical
Large potential for population
Behaviourally appropriate

Advantages :
Appropriate to individuals
Subject motivation
Physician motivation
Benefit to risk ratio is favourable

Disadvantages:
Small benefits to individual
Poor motivation of subject
Poor motivation of physician
Benefit to risk ratio may be low

Disadvantages:
High screening costs.
Temporary effects
Limited effect
Behaviourally inappropriate

Prevention Paradox
A preventive measure which brings much benefit to the
population often offers little to each participating individual.
Classical example is the Framingham study:
Data from the study suggests that if all men upto age 55
reduced their cholesterol level by 10%, 1 in 50 could
expect to avoid a heart attack on average, yet 49 out of 50
would follow the same measures and perhaps get nothing
out of it.

Secondary Prevention
These include all actions undertaken at the stage of early
pathogenesis (asymptomatic disease) with a view to halt the
progress of disease at its earliest, incipient stage, by early
diagnosis and prompt treatment.
classical example is screening for disease for breast cancer
(using mammography) and cervical cancer (using pap smear).
medical examinations of school children, of industrial workers
and various disease screening camps.

Tertiary prevention

These include all measures undertaken when the disease has become
clinically manifest or advanced, with a view to prevent or delay death,
reduce or limit the impairments and disabilities, minimize suffering and to
promote the subjects adjustment to irremediable conditions.

Tertiary prevention has two types of approaches :

disability limitation
rehabilitation.

Tertiary prevention
Disability Limitation : These include all measures to prevent
the occurrence of further complications, impairments,
disabilities and handicaps or even death. example :
Application of plaster cast to a patient who has suffered
Colles fracture, is done to prevent complications and
further disability like mal-union or non-union.
Complete rest, morphine, oxygen and streptokinase is
given to a patient of Acute MI, to prevent death or
complications like arrhythmias / CHF.

Tertiary prevention
The sequence with which a disease turns into a handicap is as
follows :
Disease : This is a pathological process and its manifestations
which indicate a departure from the state of perfect health.
Impairment : This is the actual loss or damage of a part of
body anatomy or an aberration of the physiological functions
that occurs consequent to a disease.
Disability : This is defined as the inability to carry out certain
functions or activities which are otherwise expected for that
age / sex, as a result of the impairment.
Handicap : This is the final disadvantage in life which occurs
consequent to an impairment or disability, which limits the
fulfillment of the role a person is required to play in life.

Tertiary prevention
Rehabilitation : This is the second component of tertiary
prevention.

Rehabilitation stands for the combined and coordinated usage

of all the available medical, social, educational and vocational
measures, for training the person to the highest level of
functional ability.

Tertiary prevention
Medical rehabilitation :
This is done through medical / surgical procedures to restore
the anatomy, anatomical functions and physiological functions
to as near normal as possible.
Vocational rehabilitation :
It includes steps involving training and education so as to
enable the person to earn a livelihood.
Social rehabilitation :
This involves steps for restoration of the family and social
relationships.
Emotional and Psychological rehabilitation :
This involves steps to restore the confidence, personal dignity
and confidence.

Levels of Prevention
Level of prevention

Phase of disease

Target

Primordial

Underlying condition leading

to causation

Total population and selected

groups

Primary

Specific causal factors

Total population, selected

groups and healthy
individuals

Secondary

Early stage of disease

Patients

Tertiary

Late stage of disease

Patients

Quantifying the Prognosis

Prognosis is a quantitative expression of the likelihood of a
specific outcome (survival).
Prognosis

Death

CFR

Survival

5 year
survival

Observed
survival

Median
survival

Relative
survival

Case Fatality rate

Five year survival rate

Five year survival rate

Widely used in cancer studies
Eg. The five-year survival rate for women with
Localized (stage I) breast cancer: 88%
Metastatic Stage 4 breast cancer:15%

Lead Time
Lead time is the time between the early detection of disease
(e.g by screening) and the time of its usual clinical diagnosis.
Lead time bias occurs because of the failure to account for the
lead time when calculating survival.

Observed survival rate

The observed survival rate is an estimate of the

probability of surviving.

Probability of surviving can be calculated using the technique

of life table analysis.
Advantage of using data on all patients, regardless of how
long they survive.

Median survival time

Median survival time is the length of time that half of the
study population survives.
Advantages over mean survival:
Less affected by extremes.
Have to study only half the group.

Relative survival rate

Relative survival rate is the ratio of the observed survival (rate)
to the expected survival (rate)
It compares survival in the study group (e.g., cancer) to the survival
of a comparable group without the disease of interest.
It removes from the observed survival the effect of deaths from all
other causes.
Comparison group consists of persons in the general population
similar to the patient group with respect to age, sex, and calendar
year of observation, and free of the disease of interest.

References
Parks Textbook of preventive and social medicine, 21 st edition
Textbook of Epidemiology, Leon Gordis, 4 th edition.
Textbook of public health and community medicine, AFMC,2009
Measures of prognosis, Bloomberg School of Public Health,2008
CDC , Principles of Epidemiology in Public Health Practice, 3rd
Edition