NATURAL HISTORY OF A

DISEASE

By: Donnabel L. Tubera MD, MPH

Learning Objectives
1. Define Natural History of a
Disease
2. Differentiate Natural History of a
Disease and Clinical Course of a
Disease

Natural History of the

Disease
- The evolution of the disease
without medical intervention

Natural History of Disease

This is the uninterrupted
progression in an individual of the
disease from the moment of
exposure to the causal agents.

Importance of Knowing
the History of a Disease
Guide how to prevent the
transmission
Guide in the appropriate
treatment and management
Reference or guide in case
investigation

Clinical Course of the

Disease
Describes the evolution of the
disease that has come under
medical care and is then treated in
a variety of ways that might affect
the subsequent course of events

Clinical Course of the

Disease
Describes the evolution of the
disease that has come under
medical care and is then treated in
a variety of ways that might affect
the subsequent course of events

Natural history of coronary

heart disease
Spontaneous
atherosclerosis

Chronic
minimal injury
(blood flow,
CHL, smoking,
infection?)
(youth?)

Fibrointimal
lesion

Lipid lesion

Accumulation of
lipids and
monocytes,
toxic products,
platelet
adhesion
(adolescence)
10

Plaque growth,
occlusion

Migration &
Disruption
proliferation of
thrombi
smooth
muscle cells
(adulthood)
(adulthood)

Natural history is central to

screening
Detectable,
preclinical

Pre-detectable

Age:

35

45

Possible detection
via screening

Disability
or death

Clinical

55

65

Clinical
detection

75

Natural course of type 2

diabetes
Obesity

IFG*

Diabetes

Uncontrolled Hyperglycemia

350
300

Glucose
(mg/dL)

Post-meal Glucose

250
200

Fasting Glucose

150
100
50
-10

-5

10

15

Years of Diabetes
*IFG = Impaired Fasting Glucose
15 Minnesota
Adapted from International Diabetes Center (IDC) Minneapolis,

20

25

30

Natural History:
Responses

1. Exposure may have no discernible effect.

2. There may be demonstrable damaging effect
of the exposure which may be repaired.
3. The effect may be an illness that is rapidly
contained by the body's defence mechanism.
4. The illness may progress until it leads to
continuing long term problems, irreversible
damage or death.
The outcome will depend on the interactions of
host, agent and environmental factors.

Natural History of Disease

Exposure

Onset of
symptoms

Usual time of
diagnosis

Pathologic
changes
Stage of
susceptibility

Stage of
subclinical
disease

Stage of
clinical
disease

Stage of
recovery,
disability or
death

Two Periods of Natural

History of a Disease

1. Prepathogenesis
a. Susceptibility
b. Adaptation
2. Pathogenesis
a. Presymptomatic
b. Clinical Disease
i. Incubation Period
ii. Induction period or Latency period
c. Recovery, Disability or Death

1. Prepathogenesis
Susceptibility
- Disease did not yet develop yet
- Groundwork has been laid through
presence of factors that favors its
occurrence

 Adaptation
- Initial response of the body either
at the cellular or functional level
- If responses are successful, then no
disease occurs and the process is
arrested

2. Pathogenesis
Presymptomatic Stage
- Early pathogenesis
- No symptoms indicating the
presence of illness

Inapparent Infection
Aka covert or subclinical infectionorganism multiply in the host and
cause a measurable reaction that,
however, is not clinically
detectable

Carrier
- an infected person who does not
have apparent clinical disease, but
is, nevertheless, a potential source
of infection to others

Type of Carrier
Inapparent throughout

Examples
Polio virus, meningococcus,
hepatitis viruses

Incubatory carrier

Viruses of chickenpox,
measles, and hepatits

Convalescent carrier

C.diphtheriea,hepatitis B
virus and Salmonella
species

Chronic carrier

S. typhosa, hepatitis B virus

Clinical Disease
- Disease that is detectable because
of symptoms experienced by the
patient or signs apparent to a
clinician during physical examination
- Sufficient anatomical or functional
changes have occurred to produce
recognizable signs and symptoms

Possible outcomes?
Complete Recovery
Residual defect/Disability,
Death

Obstacles to studying the

natural history of disease
Information on natural history is very
hard to obtain.
What difficulties can you see in studying
the true natural history of disease?
Would you be willing to participate in a
natural history study?
What might be the effect on you of
being in such a study?

Natural history of disease

Exposure

Onset of
symptoms

Usual time of
diagnosis

Pathologic
changes
Stage of
susceptibility

PRIMARY
PREVENTION

Stage of
subclinical
disease

SECONDARY
PREVENTION

Stage of
clinical
disease

Stage of
recovery,
disability or
death

TERTIARY
PREVENTION

Spectrum of disease
Disease may present with varying
signs, symptoms and severity.
The spectrum of disease is,
primarily, a population concept
(while natural history is primarily
a concept relating to individuals).

Iceberg/pyramid of
disease
In most diseases, as with the
iceberg, the larger presence lurks
unseen, unmeasured and easily
forgotten.
Epidemiology that forgets the
iceberg phenomenon of disease is
weak and potentially misleading.

Figure 6.6 The pyramid and iceberg of disease

Diseased, diagnosed & controlled

Diagnosed, uncontrolled

Undiagnosed or wrongly
diagnosed disease

Risk factors for disease

Free of risk factors

Diagnosed
disease

Undiagnosed or
wrongly diagnosed disease

 Patients who are at the tip of the

iceberg are more likely to have multiple
health problems than others.
People with cardio-respiratory problems
and diabetes are more likely to be
admitted to hospital, than people with
only one of these two problems. This is
the basis of the bias known as Berkson's
bias.

Figure 6.7

Diseased, diagnosed & controlled

Nil, except vigilance

Review

Opportunistic
or population
screening

Screening
education or health

4 Risk factors for disease

Protection
of current
status

5 Free of risk factors

2 Diagnosed, uncontrolled
3 Undiagnosed or wrongly
diagnosed disease

Summary
Natural history of disease is the
uninterrupted progression of disease
from its initiation by exposure to the
causal agents to either spontaneous
resolution, containment by the bodys
repair mechanisms, or to a clinically
detectable problem.
The primary purpose of public health
and medicine is to influence favourably
the natural history of disease.

Summary
For most health problems the
number of cases identified is
exceeded by those not discovered.
The iceberg phenomenon thwarts
epidemiological efforts to assess
the true burden of disease.

Summary
Natural history of disease is
related to (and influences) the
changing pattern of disease in
populations or the different levels
of severity with which a disease
may present (spectrum of
disease).

Any questions?