Detail of natural history of disease

1. NATURAL HISTORY OF DISEASE

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

3. 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.

4. Exposure host disease
recovery
disability
death
Natural History of Disease

5. 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.

6. 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.

7. 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.

8. 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.

9. ICEBERG CONCEPT OF
DISEASE
DEATH
SEVERE
DISEASE
MILD ILLNESS
INFECTION WITHOUT
CLINICAL ILLNESS
EXPOSURE WITHOUT INFECTION
CLINICAL
DISEASE
SUBCLINICAL
DISEASE

10. Models of disease causation

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

12. 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

13. Epidemiological Triad

14. Epidemiological Triad

15. 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.

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

17. 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.

18. 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 life-threatening 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

19. 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 individual’s
exposure, susceptibility, or response to a causative agent.

20. 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.

21. AGENT HOST FACTORS
ENVIRONMENT FACTORS
1.Poor housing
2.Overcrowding
3.Poverty
4.Urbanization
1.Decreased
immunity
2.Malnutrition
3.Elderly
4.HIV infection
M. Tuberculosis

22. Epidemiological Tetrad
• Agent
• Host
• Environment
• Time

23. 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)

24. 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).

25. 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.

26. 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.

27. 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.

28. Web of Causation applied to Myocardial Infarction

29. Example of Web of Causation
Susceptible Host Infection Tuberculosis
Vaccination Genetic
Overcrowding
Malnutrition
Tissue Invasion and
Reaction
Exposure to
Mycobacterium

30. 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

31. 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.

32. 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.

33. Wheel Theory

34. Wheel Theory

35. Factors of disease causation

36. 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.

37. 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.

38. Exposure to
TB
Infection(10-30%)
No infection(70-90%)
Active TB(10% ill)
-5% develop TB within 2 years
-5% develop TB many years later
Latent TB (90% well)
-Never develop TB
-Not infectious
Treated
Untreated
Cured
50% die within 5 years
25% remain sick
25% recover

39. The Natural history of disease in
man

40. (A) (P) (S) (M) (D) (T)
The Natural history of disease in a patient
• 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
Preclinical Phase Clinical Phase
Gordis L. Epidemiology. WB Saunders Company. 1996

45. 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.

46. Primary prevention
• Measures of prevention undertaken during the phase of pre-
pathogenesis (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.

47. 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.

48. 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

49. 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.

50. Primary prevention
• Two types of strategy:
– Population strategy
– High risk strategy

51. Primary prevention
Population strategy
Advantages:
Radical
Large potential for population
Behaviourally appropriate
Disadvantages:
Small benefits to individual
Poor motivation of subject
Poor motivation of physician
Benefit to risk ratio may be low
High risk strategy
Advantages :
Appropriate to individuals
Subject motivation
Physician motivation
Benefit to risk ratio is favourable
Disadvantages:
High screening costs.
Temporary effects
Limited effect
Behaviourally inappropriate

52. 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.

53. 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 it’s 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.

54. 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 subject’s adjustment to irremediable conditions.
• Tertiary prevention has two types of approaches :
– disability limitation
– rehabilitation.

55. 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
Colle’s 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.

56. Tertiary prevention
• The sequence with which a disease turns into a handicap is as
follows :
– Disease : This is a pathological process and it’s 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.

57. 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.

58. 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.

59. 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

61. 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

62. Case Fatality rate

63. Five year survival rate

64. 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%

65. 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.

66. 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.

67. 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.

68. 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.

69. References
• Park’s Textbook of preventive and social medicine, 21st edition
• Textbook of Epidemiology, Leon Gordis, 4th 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