1st Bimonthly: PSM

LECTURE SERIES
Lecture series 1.
Introduction to epidemiology

Definition of health

 The physical, mental and social well-being of the individual and not merely the absence
of disease. (WHO)

 Balance in the relationship between the body, mind, and complete adaptation to the total
environment.

 Physical well-being –individual is free from disabling disease and has ability to perform
daily tasks and physiologic activities (respiration, circulation, nutrition, digestion,
metabolism, thinking)

 Mental well-being – be comfortable about one’s self, acceptance of shortcomings, have

self-respect, feel right about other people, consider interests of others, have satisfying
interpersonal relationships, have sense of social responsibility, can meet demands of life,
do something about problems as they arise, put up realistic goals for themselves.

 Social well-being – ability to live in harmony with himself and society. Can provide and
secure physiologic needs, food, clothing, shelter, recreation, medical care.

Definition of preventive medicine

 The science and art of disease prevention and health promotion.

 Disease prevention – deals with techniques that prevent the occurrence of disease or lead
to an early diagnosis where therapy may cure, prevent or modify the progression of
disease.

 Health promotion – techniques that foster physical and emotional well-being. Many
diseases are caused by personal, modifiable lifestyle habits such as poor diet, infrequent
exercise, unprotected sexual intercourse, lack of prenatal care, use of tobacco, alcohol,
drugs.

Two areas of preventive medicine

 Public health – application of preventive medicine methods to a population. Programs

and activities of government or community groups not normally done by the private
sectors that improve the health status of the community or individuals in the community.
  Risk factor evaluation – programs and activities directed at individuals who may have
high-risk factors (smoking, drug abuse, obesity) that cause disease, and educate them
about good health habits, and screen them for illnesses (e.g., hypertension, cancers).

Public health

 Science and art of preventing disease, prolonging life, and promoting mental and physical
health and efficiency through organized community efforts for the following:

1. Health promotion activities

2. Environmental sanitation, personal hygiene
3. Control of communicable diseases
4. Organization of medical and nursing services for the early diagnosis and
preventive treatment of diseases
5. Development of social machinery to ensure to every individual a standard of
living adequate for the maintenance of health, to realize his right of health.

Epidemiology

Definition

 the study of the distribution and determinants of health-related states or events in

specified populations and the application of this study to the control of health problems.

 Epidemiology is the task of using data to answer questions of:

Who is getting sick? (distribution):
What is making people sick? (deteminants) and
How can we use this information to reduce the risk of others getting sick? (public health)

 Without quality health data, it is very difficult to answer these questions. A surveillance
system that serves to collect health data in a complete and timely manner is thus essential
to the practice of epidemiology.

 Surveillance: the ongoing systematic collection, analysis, and interpretation of outcome-

specific data for use in planning, implementation, and evaluation of public health
practice.”

 A fundamental science of public health, goal is to promote health, prevent and control
disease, is achieved through studies that examine the relationship of disease and factors
in the population.

Uses of epidemiology

1. Identify and measure the importance of health problems, describe the high
risk groups, and explain the cause of these problems.
 2. Understand the natural history of disease
3. Essential for disease surveillance and control
4. Contributes to the planning, monitoring and evaluation of health services.
5. Key instrument in the formulation of health policies.

Goals of an epidemiologist

 Identify factors that cause disease or disease transmission.

 Prevent the spread of communicable and non-communicable diseases and conditions.
 He identifies and prevents disease in given population, while a clinician identifies and
treats disease in an individual.

Lecture series 2

A. Disease Causation

Disease is multi-factorial in nature and that many factors and events contribute to ill
health. Epidemiologic triangle or ecologic triad – a model of disease causation. In order for a
disease process to occur, there must be a combination of events – a harmful agent that comes
into contact with a susceptible host in the proper environment.

Agents of Disease
a. Biologic (microorganisms)
b. Chemical (toxins, poisons)
c. Nutritional (excess food, lack of food, vitamin deficiency
d. Physical forces (automobiles)
e. Energy ( ionizing radiation)

Host Factors
a. Biologic traits – genetic characteristics: age, race, sex
b. Social traits – marital status, lifestyle, diet, habits

Environmental Factors
a. Physical factors – climate, setting (urban, rural), pollution
b. Biologic factors – necessary to maintain the agent or allow for
its transmission.
c. Social factors – political, social, economic

Environment refers to all external conditions and influences affecting the life of living
things. Physical, biological, and socio-economic environments provide reservoirs where agents
reside or reproduce, or both, and modes of transmission for transporting agents from the
reservoir to a human host.
 The physical environment includes the geological structure of an area and the availability
of resources, such as water and flora, that influence the number and variety of animal reservoirs
and certain insects that function as vectors to carry an agent from the reservoir to the host.
Weather, climate and season are important influences in the physical environment.

The biologic environment, which includes living plants and animals that may serve as
either the reservoir (environment in which an infectious agent normally lives and multiplies, is
dependent for survival, and reproduces) or the vector (living carrier that transports an infectious
agent from an infected individual or its wastes to a susceptible individual or its food or
immediate surroundings) for transmission of an infectious agent. Dengue fever is caused by a
virus that is transmitted through the bite of a mosquito.

The socio-economic environment contributes to the types of infectious agent in a locality

because social and economic conditions relate both to the extent of environmental sanitation
practices, such as disposal of garbage and excreta, and to the availability of medical facilities for
immunization and medical care.

B. Natural history of disease

Occurrence of disease in a human host is not a single event at one point in time. Rather,
it is a process occurring over a period of time – the natural history of disease.

The natural history may be divided into two periods, prepathogenesis and pathogenesis.
Each of these periods is further subdivided into two stages.

Natural history of disease

Prepathogenesis Pathogenesis

Susceptibility Adaptation Early Clinical disease

Pathogenesis

Exposure Early Late

Clinical stage Clinical stage
Incubation period

Early Diagnosis
detection occurs
possible

Symptom
onset
 Prepathogenesis. In the first stage, susceptibility, disease has not yet developed,
although the groundwork has been laid through presence of factors that favor its occurrence. For
example, poor eating habits and fatigue resulting from lack of sleep, which are often present
among college students during exam week, represent risk factors that favor the occurrence of the
common cold. If exposure to an agent occurs at this time, a response will occur. Initial
responses reflect the normal adaptation response of the cell or functional system (e.g., the
immune system). If these adaptation responses are successful, then no disease occurs and the
process is arrested in the second stage of prepathogenesis.

Pathogenesis. In early pathogenesis, the individual has no symptoms indicating the

presence of illness. Adaptation, however, has been unsuccessful and pathogenic changes have
begun. These changes, which may be detectable by sophisticated laboratory tests, are called
subclinical because they are below the level of the clinical horizon, an imaginary line dividing
the point where there are detectable signs and symptoms from that where there are not.

Clinical disease is defined as disease that is detectable because of symptoms experienced

by the patient or signs apparent to a clinician during a physical examination. By this stage,
sufficient anatomical or functional changes have occurred to produce recognizable signs and
symptoms. This stage includes a range of disease severity from early clinical disease to that so
advanced that death is inevitable. Possible outcomes, once a patient has entered this stage, may
be complete recovery, residual defect that produces some degree of disability or death.

Exposure of the host to an agent occurs during the stage of susceptibility. In the case of
infectious agents, exposure is followed by an incubation period, a time when the organism
multiples to sufficient numbers to produce a host reaction and clinical symptoms. This time
period is relatively short, usually hours to months. The end of the incubation period is the point
of disease detection, whether by screening or by appearance of clinical signs and symptoms.

Most, but not all, diseases with infectious causes are of relatively short duration. The
patient is usually ill for a period ranging from a few days to several months and generally
recovers without any residual disability, or if the illness was severe, may die from the illness.
The patient who has recovered rarely requires long-term follow-up, although there are
exceptions. Tuberculosis and rheumatic heart disease result from a staphylococcal infection, are
diseases caused by infectious agents that are chronic in nature.

C. Levels of Prevention

The natural history of a disease provides the basis for planning intervention. Because a
disease evolves over time and pathological change becomes less reversible as the disease process
continues, the ultimate aim of intervention programs is to halt or reverse the process of
pathological change as early as possible, thus preventing further damage. Three levels of
prevention, based on the three stages of disease natural history, have proved useful. The goal of
intervention at each level is to prevent the pathogenic process from evolving further; the three
levels are called primary, secondary and tertiary prevention.
 Primary prevention is aimed at intervening before pathological changes have begun,
during the natural history of susceptibility. Primary prevention uses measures aimed at (1)
preventing the spread of the infectious agent from those environments that harbor it to
individuals who are susceptible and who may be exposed, and (2) increasing host resistance.

These aims are accomplished through two types of activities: general health promotion
and specific protection. General health promotion includes all activities that modify or eliminate
the environment in which the infectious agent lives and that interfere with the means of
transmission to the human host. Health education aimed at educating the population about good
nutrition, hygiene, the need for rest and recreation, preparation for retirement, or the harmful
effects of smoking or drug use is a form of general health promotion. Specific protection refers
to measures aimed at increasing host resistance or protecting individuals against specific agents.
These measures include immunization against specific disease, such as diphtheria or polio, and
removal of harmful agents from the environment, as with sewage treatment, pasteurization of
milk, or chlorination of water.

Secondary prevention seeks to detect disease early, treat promptly, and cure disease at its
earliest stage or, when cure is not possible, to slow its progression, prevent complications, and
limit disability. Secondary prevention is thus focused primarily on the stage of presymptomatic
disease or on the very early stage of clinical disease. Screening is the most common form of
secondary prevention. Example is the skin test for tuberculosis.

Surveillance programs are also part of secondary prevention. Such programs aimed at
controlling infectious diseases quickly identify new cases and follow up existing cases to
prevent exposure of susceptibles, and institute specific treatments to limit the period of
communicability and progression of pathology.

Tertiary prevention includes limitation of disability and rehabilitation of those persons for
whom residual damage already exists. Tertiary prevention plays a smaller role in infectious
disease programs than in non-infectious programs because infectious disease less often results in
permanent disability.

Levels of Prevention

Period Stage Level of prevention Specific intervention

Prepathogenesis Susceptibility Primary prevention Health promotion (health

education, nutrition,
hygiene, etc.
Specific protection
(immunization)
Adaptation

Pathogenesis Early
Pathogenesis
 Discernible Secondary prevention Early diagnosis and
Early lesions prompt treatment

Clinical Tertiary prevention Disability limitation

Disease Rehabilitation
D. The infectious disease process

Six components of the infectious disease process: agent, host, reservoir, mode of
transmission, portal of entry, portal of exit.

The agent

An agent is a factor whose presence causes a disease. Certain characteristics of agents

affect their ability to produce disease in the host, that is, infectivity, pathogenicity, virulence and
immunogenicity:

Infectivity is the ability of an agent to invade and multiply (produce infection) in a host.
An example of an infection of high infectivity is measles; one of low infectivity is leprosy.
Experimentally, infectivity may be thought of as the minimum number of particles or agents
required to establish infection in 50 percent of a group of hosts of the same species. This number
varies with the agent, route of administration of the agent, source of the agent, and with many
host factors such as age and race.

Pathogenicity is the ability to produce clinically apparent illness. If a population is

studied by laboratory methods during and/or following an outbreak of a particular disease for
which reliable, sensitive and specific laboratory diagnostic methods exist, the pathogenicity or
proportion of infections resulting in clinical disease can be determined. As was noted for
infectivity, many host and environmental factors as well as the dose, route of entrance of the
infection, and source of the infection may alter the pathogenicity of a particular infectious agent
or disease. For example, staphylococci are not pathogens when located in the rectum, but the
same organism found in the peritoneal cavity or meninges would cause severe illness.

The pathogenetic effects produced by infectious agents may result from a variety of
mechanisms, among which are, (1) direct tissue invasion, (2) production of a toxin, (3),
immunologic enhancement or allergic reaction leading to damage to the host, (3) persistent or
latent infection, (5) enhancement of host susceptibility to drugs of otherwise minimal toxicity,
and (6) immune suppression.

Parasitic diseases such as amoebiasis, giardiasis, many nematodes, trematodes, and

cestodes, bacterial meningitis, urinary tract infection, phargyngitis, skin abscess, viral infections
such as upper respiratory tract and gastrointestinal viruses are examples of diseases that are
produced by direct invasion of tissue. Examples of toxin production are tetanus, diphtheria,
staphylococcal food poisoning. Diseases that are thought to have significant immunologic
components are tuberculosis, and post-streptococcal glomerulonephritis. Examples of persistent
or latent infection are Hemophilus influenzae (persist asymptomatically in the pharynx),
Salmonella species in the GIT, and E. coli in the urinary tract. Persistent viral infections include
herpes I and II, varicella zoster, hepatitis B. When some stress, hormonal, or environmental
factor alters the host-cell regulatory mechanisms, then production of complete viruses occurs and
may result in clinical disease. An infectious agent may produce severe disease by sensitizing
the host to otherwise relatively nontoxic drugs. Such is thought to be a possible pathogenetic
mechanism in Reye’s syndrome, in which infection by such viral agents as varicella and
influenza B viruses may result in severe disease (encephalopathy) when the patient is treated
with medication containing salicylates. Lastly, immune suppression is exemplified by AIDS
which has a case fatality rate estimated at 70 percent.

Virulence is the proportion of clinical cases resulting in severe clinical manifestations

(including sequelae). The case fatality rate is one way of measuring virulence. Virulence may
depend on dose, route of infection, and host factors such as age or race. Example, infection with
Neisseria meningitides or Neisseria influenzae would be much severe if they enter the brain
through a fracture in the cribriform plate than if they simply enter through the nasopharynx.

Immunogenicity is infection’s ability to produce specific immunity. Depending on the

type of pathogen, this may be primarily humoral immunity, cellular immunity, or a mixture of
both. Immunogenicity can be affected by host factors such as age, nutrition, dose and virulence
of infection. Agents that replicate in local areas such as the respiratory tract (rhinovirus), genital
tract (gonococci), or gastrointestinal mucosa may produce only local and not systemic, immune
responses. Agents also differ in their intrinsic ability to induce an effective, lasting immune
response. For example, the agent of measles produces lifelong immunity, whereas gonococci
have no such ability and it is therefore possible to have multiple attacks of gonorrhea.

The host

A host is the individual human in whom an agent produces disease. Disease can occur
only in a host who is susceptible. Lack of susceptibility may be due to immunity or to inherent
resistance. Immunity relates to lack of susceptibility to infectious agents, whereas inherent
resistance is broader, including lack of susceptibility to all types of agents.

Immunity is the resistance on the part of a host to a specific infectious agent. Immunity
can be humoral (antibodies in the blood) or cellular (specific to each type of cell). The role of
immunity varies with the type of infectious agent. Immunity can be passive or active.

Inherent resistance refers to the ability to resist disease independently of antibodies or of

specifically developed tissue response. It commonly rests in anatomical or physiological
characteristics of the host; it may be genetic or acquired, permanent or temporary. The concept
of inherent resistance is useful in understanding host resistance both to infectious agents and
other types of agents. Factors such as general health status or nutrition, for example, may affect
resistance to disease. Someone in good health who maintains good nutrition and a regular
schedule of rest and exercise may be exposed to the common cold virus and resist infection event
though the person is not immune to the organism.
Reservoir
 Reservoirs may be defined as the living organisms or inanimate matter (such as soil) in
which an infectious agent normally resides and multiplies. Reservoirs consist of human beings,
animals, and environmental sources. The reservoir is an essential component of the cycle by
which an infectious agent maintains and perpetuates itself. The specific reservoir for an agent is
thus intimately related to the life-cycle of that agent in nature.

In the simplest cycle, the reservoir is the human, and the cycle may be diagrammed as
follows: human  human  human. This type of cycle is characteristic of many of the
common infectious diseases to which humans are subject: most of the viral and bacterial
respiratory diseases, most staphylococcal and streptococcal infections, diphtheria, venereal
diseases, childhood exanthems, mumps, amebiasis, etc.

Diseases that are acquired from other species include leptospirosis (from rodents), and
rabies (from dogs, bats, foxes, other wild animals). These diseases are known as zoonosis,
infections transmissible under natural conditions from vertebrate animals to man. In these
diseases, the human is not an essential part (usual reservoir) of the life-cycle of the agent. Thus:
animal  animal  animal
 human

Certain other infectious diseases are characterized by more complex cycles. Features
may include multiple reservoirs and different developmental stages of the agent. Examples are
tapeworm infestations, schistosomiasis, malaria, and vector-borne infections.

Humans as reservoirs: cases and carriers. Infection is said to have occurred if an

infectious agent has entered and established itself in a host. A range of reactions to this
occurrence is possible. At a minimal level, the agent may be present on the surface of the body
and propagate at a rate sufficient to maintain its numbers without producing identifiable evidence
of any reaction in the host. This phenomenon, called colonization, is exemplified by the
presence of Staphylococcus aureus on the nasal mucosa.

At the next level is inapparent infection (covert or subclinical infection). The

organisms not only multiply in the host, but also cause a measurable reaction that, however, is
not clinically detectable. When infection leads to clinical (overt) disease with symptoms,
physical findings, or both, infectious disease is said to exist. Thus, infection encompasses (1)
colonization, (2) inapparent infection, and (3) infectious disease.

All infected persons, including those with colonization only, are potential sources of
infection to others. A carrier is an infected person who does not have apparent clinical disease,
but is nevertheless, a potential source of infection to others. The types of carriers are as follows:
Type of carrier Examples
Inapparent throughout Polio virus, meningococcus, hepatitis viruses
Incubatory carrier Viruses of chickenpox, measles, hepatitis
Convalescent carrier C. diphtheriae, hepatitis B, Salmonella species
Chronic carrier S. typhosa, hepatitis B virus

Modes of transmission of infection

 A central aspect of the spread of infectious disease is transmission of infection, or the
various mechanisms by which agents reach and infect the human host. This involves escape of
the agent from a source of reservoir, conveyance to a susceptible host, and entry into that host.
Transmission may be direct or indirect.

Direct transmission consists of essentially immediate transfer of an infectious agent

from an infected host or reservoir to an appropriate portal of entry. This may involve direct
contact such as kissing and sexual intercourse, and droplets through sneezing and coughing onto
the mucous membranes of others. Such droplet spread is classified as direct transmission
because it occurs over short distances – the droplets travel only a few feet before falling to the
ground. Direct transmission also includes exposure of susceptible tissues to fungal agents,
bacterial spores, or other parasites (e.g., hookworm) lying the soil or vegetation.

Sexually transmitted diseases (STDs) are spread by direct transmission. Examples are
syphilis, gonorrhea, infections caused by Chlamydia trachomatis, Trichomonas vaginalis, and
herpes simplex types I and II. Sexual practices such as orogenital contact and anal intercourse,
when combined with promiscuity, have contributed to increased sexual transmission of hepatitis
B, herpes simplex type II, amebiasis and shigellosis. Acquired immune deficiency syndrome
(AIDS) may fall into this category as well. Some groups of homosexual males have been shown
to be at especially high risk for these diseases.

Other risk factors for AIDS are frequent sexual contact with different partners,
intravenous drug use and blood transfusions.

Indirect transmission may be vehicleborne, vectorborne or airborne. Vehicleborne

transmission is indirect contact through inanimate objects (fomites) such as beddings, toys or
surgical instruments, as well as contaminated food, water, and intravenously administered fluids.
The agent may or may not multiply or develop in or on the vehicle before it is introduced into the
human.

In vectorborne transmission, the infectious agent is conveyed by an anthropod to a

susceptible host. The arthropod may merely carry the agent mechanically, by soiling its feet or
probroscis, in which case multiplication of the agent in the vector does not occur. The vector
may also be truly biological if the agent multiplies in the arthropod before it is transmitted. In
this case, there is an incubation period in the arthropod, known as the extrinsic incubation period,
before the arthropod can become infective.

Finally, indirect transmission may be airborne. Two types of particles are implicated in
this kind of spread – dusts and droplet nuclei. Dusts are particles of varying size that result from
resuspension of particles that have settled on floors or bedding as well as particles blown from
the wind.

Droplet nuclei are very tiny particles that represent the dried residue of droplets. They
may be formed in several ways. One is from the evaporation of droplets that have been coughed
or sneezed into the air.
 Airborne infection is important in a number of diseases. For example, coughing by a
person with an open cavity, tuberculous lesion can result in the formation of droplets that travel
only a few feet and then either fall to the ground or are inhaled (direct contact). Because of their
large size, these droplets, if inhaled, are promptly removed from the upper airways. However,
some droplets form droplet nuclei that can be inhaled directly into the alveoli.

Lecture series 3.

Communicable disease control

Definition of Terms1

1. Carrier – a person or animal that harbors a specific infectious agent without discernible
clinical disease and serves as a potential source of infection. There are four carrier states,
namely:
a. subclinical carrier – patient who never develops clinical symptoms of disease.
e.g., polio virus, hepatitis
b. incubatory carrier – patient incubating a communicable disease who may transmit
the infection shortly before he becomes symptomatic.
E.g., chickenpox, measles
c. convalescent carrier – patient who has recovered from an acute illness and may
continue to shed the organism. E.g., diphtheria, Salmonella typhi
d. chronic carrier – patient who may develop chronic infection and transmit the
infection for long periods of time, usually over one year.
E.g., Salmonella typhi, hepatitis B virus, HIV/AIDS.

2. case fatality rate – usually expressed as the percentage of persons diagnosed as having a
specified disease who died as a result of that disease within a given period of time. This term is
most frequently applied to a specific outbreak of acute disease in which all patients have been
followed for an adequate period of time to include all attributable deaths. The case-fatality rate
must be clearly differentiated from the mortality rate.

3. Communicable disease – an illness due to a specific infectious agent or its toxic products
that arises through transmission of that agent or its products from an infected person, animal or
inanimate reservoir to a susceptible host, either directly or indirectly through an intermediate
plant or animal host, vector or the inanimate environment. (synonym: infectious disease).

4. Communicable period – the time during which an infectious agent may be transferred
directly or indirectly from an infected person to other person, from an infected animal to human,
or from infected person to animals, including arthropods.

1
Readings and Handouts in Epidemiology. Department of Epidemiology and Biostatistics.
College of Public Health. University of the Philippines. June 2002.
In disease such as diphtheria and streptococcal infections, in which mucous membranes are
involved from the initial entry of the infectious agent, the period of communicability is from the
date of first exposure to a source of infection until the infecting microorganisms is no longer
disseminated from the involved mucous membranes, i.e., from the prodromal period until
termination of a carrier state, if the latter develops. Some diseases are more communicable
during the incubation period than during the actual illness (e.g., hepatitis A, measles).

In diseases such as tuberculosis, leprosy, syphilis, gonorrhea and some of the salmonelloses, the
communicable state may exist for a long and sometimes intermittent period when active chronic
lesions permit the discharge of infectious agents from the surface of the skin or through any of
the body orifices.
In diseases transmitted by arthropods, such as malaria, the periods of communicability or more
properly infectivity, are those during which the infectious agent occurs in the blood or other
tissues of the infected person in sufficient numbers to permit infection of the vector. A period of
communicability is also to be noted for the arthropod vector, namely, when the agent is present
in the tissues of the arthropod in such form and focus (infective state) as to be transmissible.

5. Contact – a person or animal that has been in such association with an infected person or
animal or a contaminated environment as to have had an opportunity to acquire the infection.

6. Contamination – the presence of an infectious agent on a body surface, in clothes, bedding,

toys, surgical instruments or dressings, or other inanimate articles or substances including water
and food.

7. Control – as applied to many communicable diseases, means ongoing operations or programs

or public health activity aimed at and achieving a decrease of the incidence of a disease to a point
when it does not present a serious health problem to the community, although the transmission of
the pathogen may continue.

8. Endemic – the constant presence of a disease or infectious agent within a given geographic
area; it may refer to the usual prevalence of a given disease within such area. Hyperendemic
expresses a constant presence at a high level of incidence, and holoendemic a high level of
prevalence with infections beginning early in life and affecting most of the population (e.g.,
malaria in some places).

9. Epidemic – the occurrence in a community or region of cases of an illness (or an outbreak)

with a frequency clearly in excess of normal expectancy. The number of cases indicating
presence of an epidemic will vary according to the infectious agent, size and type of population
exposed, previous experience or lack of exposure to the disease, and time and place of
occurrence. Epidemicity is thus relative to usual frequency of the disease in the same area,
among the specified population, at the same season of the year. A single case of a
communicable disease long absent from a population or in the first invasion by a disease not
previously recognized in that area requires immediate reporting and epidemiologic investigation;
two cases of such a disease associated in time and place are sufficient evidence of transmission
to be considered an epidemic.
10. Eradication – interruption of transmission of a pathogenic agent followed by the
elimination or extinction of the disease caused by it. This implies that infection has disappeared
because transmission of the causative agent has ceased in an irreversible manner.

11. Elimination – is sometimes used to describe eradication of diseases such as measles from a
large geographic region or political jurisdiction.
12. Herd immunity – the immunity of a group or community. The resistance of a group to
invasion and spread of an infectious agent, based on the resistance to infection of a higher
proportion of individual members of the group.
13. Host – A person or other living animal, including birds and arthropods, that affords
subsistence or lodgment to an infectious agent under natural (as opposed to experimental)
conditions. Some protozoans and helminths pass successive stages in alternate hosts of different
species. Hosts in which the parasite attains maturity or passes its sexual stage are primary or
definitive hosts; those in which the parasite is in a larval stage or asexual stage are secondary or
in intermediate hosts.

14. Immune individual – A person or animal that has specific protective antibodies and/or
cellular immunity as a result of previous infection or immunization, or is so conditioned by such
previous specific experience as to respond in such a way that prevents the development of
infection and/or clinical illness following reexposure to the specific infectious agent.

15. Immunity – that resistance usually associated with the presence of antibodies or cells
having a specific action on the microorganism concerned with a particular infectious disease or
on its toxin. Effective immunity includes both cellular immunity which is conferred by T-
lymphocyte sensitization, and/or humoral immunity, which is based on antibodies in the blood.
Passive immunity is attained either naturally by transplacental transfer from the mother (passive
natural), or artificially by inoculation (passive artificial) of specific protective antibodies (from
immunized animals, or convalescent hyperimmune serum or immune serum globulin [human]).
Passive immunity is of short duration – days to months. Active immunity, which usually lasts
for years, is attained either naturally by infection (active natural) with or without clinical
manifestations or artificially (active artificial) by inoculation of the agent itself, which is killed,
modified, or in variant form, or fractions or products of the agent.

16. Inapparent infection – the presence of infection in a host without recognizable clinical
signs or symptoms. Inapparent infections are identifiable only by laboratory means such as
blood tests or development of positive reactivity to specific skin tests. (synonyms:
asymptomatic, subclinical)

17. Incidence rate – the number of new cases of a specified disease diagnosed or reported
during a defined period of time, divided by the number of persons in a stated population in which
the cases occurred. This is usually expressed as cases per 1,000 or 100,000 per annum.

Attack rate, or case rate, is a proportion measuring cumulative incidence often used for
particular groups, observed for limited periods and under special circumstances, as in an
epidemic; it is usually expressed as percent (cases per 100 in the group). The secondary attack
rate is the number of cases among familial or institutional contacts occurring within the accepted
incubation period following exposure to a primary case, in relation to the total of exposed
contacts; the denominator may be restricted to susceptible contacts when determinable.
Infection rate is a proportion that expresses the incidence of all identified infections, manifest
and inapparent.

18. Incubation period – the time interval between initial contact with an infectious agent and
the first appearance of symptoms associated with the infection. In a vector, it is the time
between entrance of an organism into the vector and the time when that vector can transmit the
infection (extrinsic incubation period). The period in people between the time of exposure to a
parasite and the time when the parasite can be detected in blood or stool is called the prepatent
period.

19. Infected individual – a person or animal that harbors an infectious agent and who has either
manifest disease (patient or sick person) or inapparent infection (carrier). An infectious person
or animal is one from whom the infectious agent can be naturally acquired.

20. Infection- the entry and development of an infectious agent or its multiplication in the
body of persons or animals. Infection is not synonymous with infectious disease; the result may
be inapparent (see inapparent infection) or manifest (see infectious disease). The presence of
living infectious agents on exterior surfaces of the body or on articles of apparel or soiled articles
in not infection, but represents contamination of such surfaces and articles.

21. Infectious agent - an organism is capable of producing infection or infectious disease.

Infectivity expresses the ability of the disease agent to enter, survive and multiply in the host,
infectiousness indicates the relative ease with which a disease is transmitted to other hosts.

22. Infectious disease – A clinically manifest disease of humans or animals resulting from an
infection.

23. Isolation – as applied to patients, isolation represents separation, for the period of
communicability, of infected persons or animals from others in such places and under such
conditions as to prevent or limit the direct or indirect transmission of the infectious agent from
those infected to those who are susceptible to infection or who may spread the agent to others.
In contrast, quarantine applies to restrictions on the healthy contacts of an infectious case.

The Center for Disease Control (CDC) in the United States recommends that universal
precautions be used consistently for all patients (in hospital settings as well as outpatient
settings) regardless of their bloodborne infection status. This practice is based on the
possibility that blood and certain body fluids of all patients are potentially infectious for HIV,
HBV and other bloodborne pathogens.

24. Pathogenicity - The property of an infectious agent that determines the extent to which
overt disease is produced in an infected population, or the power of an organism to produce
disease.
25. Quarantine – restriction of the activities of well persons or animals who have been exposed
to a case of communicable disease during its period of communicability, i.e., contacts, to prevent
disease transmission during the incubation period if infection should occur.

a. Absolute or complete quarantine – the limitation of freedom of movement of those exposed

to a communicable disease for a period of time not longer than the longest usual incubation
period of that disease, in such manner as to prevent effective contact with those not so exposed.

b. Modified quarantine – a selective, partial limitation of freedom of movement of contacts,

commonly on the basis of known or presumed differences in susceptibility and related to the
danger of disease transmission. It may be designed to accommodate particular situations.
Examples are exclusion of children from school, exemption of immune persons from provisions
applicable to susceptible persons or restriction of military populations to the post or to quarters.
It includes: Personal surveillance, the practice of close medical or other supervision of contacts
to permit prompt recognition of infection or illness but without restricting their movements, and
Segregation, the separation of some part of a group of persons or domestic animals from the
others for special consideration, control or observation, removal of susceptible children to homes
of immune persons, or establishment of a sanitary boundary to protect.

26. Reservoir - any person, animal, arthropod, plant, soil or substance (or combination of
these) in which an infectious agent normally lives and multiplies, on which it depends primarily
for survival, and where it reproduces itself in such manner.

27. Resistance – the sum total of body mechanisms that interpose barriers to the invasion or
multiplication of infectious agents, or to damage by their toxic products. Inherent resistance –
an ability to resist disease independent of immunity or of specifically developed tissue responses;
it commonly resides in anatomic or physiologic characteristics of the host and may be genetic or
acquired, permanent or temporary.

28. Source of infection – the person, animal, object or substance from which an infectious agent
passes to a host.

29. Surveillance of disease – as distinct from surveillance of persons, surveillance of disease is

the continuing scrutiny of all aspects of occurrence and spread of a disease that are pertinent to
effective control. Included are the systematic collection and evaluation of:

a. morbidity and mortality reports.

b. special reports of field investigation of epidemics and of individual cases.
c. isolation and identification of infectious agents by laboratories.
d. data concerning the availability, use and untoward effects of vaccines and toxoids, immune
globulins, insecticides and other substances used in control.
e. information regarding immunity levels in segments of the population, and
f. other relevant epidemiologic data. A report summarizing the above data should be prepared
and distributed to all cooperating persons and others with a need to know the results of the
surveillance activities.
30. Susceptible – a person or animal not possessing sufficient resistance against a particular
pathogenic agent to prevent contracting infection or disease when exposed to the agent.

31. Suspect – in infectious disease control, illness in a person whose history and symptoms
suggest that he or she may have or be developing a communicable disease.

32. Virulence – the degree of pathogenicity of an infectious agent, indicated by case-fatality

rates and/or ability of the agent to invade and damage tissues of the host.

33. Zoonosis – an infection or infectious disease transmissible under natural conditions from
vertebrate animals to humans.
Lecture series 4.

Herd immunity

• Term used to express the immunity of a group or community.

• It is the resistance of a group to invasion and spread of an infectious agent, based on the
immunity of a high proportion of individual members of the group.

• Type of immunity that occurs when the vaccination of a portion of the population (or
herd) provides protection to unvaccinated individuals.

• In diseases passed from person-to-person, it is more difficult to maintain a chain of

infection when large numbers of a population are immune. The more immune individuals
present in a population, the lower the likelihood that a susceptible person will come into
contact with an infected individual.

• During the course of an epidemic, a number of susceptible people come down with the
disease, thus providing multiple sources of infection to others. However, since the
disease victims develop immunity, as the epidemic progresses the proportion of
nonsusceptibles in the population increases and the likelihood of effective contact
between patients with the disease and remaining susceptibles declines.

• Vaccination acts as a sort of “firebreak" in the spread of the disease, slowing or

preventing further transmission of the disease to others.

• For example, if Person A had a disease and exposed Person B who was immune because
of vaccination, Person B would not get ill and could not pass on the disease to Person C
when he comes into contact with him. So even if Person C is not vaccinated, he indirectly
gets protection from the disease. Hence herd immunity may be used to reduce spread of
an illness and to protect a vulnerable, un-vaccinated subgroup. (see diagram)

• It is the general aim of public health to establish herd immunity in most populations.
 Epidemics

Definition:

• Occurrence in a community or region of cases of an illness, specific health-related

behavior, or other health-related events clearly in excess of normal expectancy. Simply,
it is an increase in the number of cases over past experience for a given population, time
and place. This time period may be either short or long so that both acute and chronic
illness, irrespective of the incubation or induction period, may occur in epidemics or in
epidemic cycles. Examples: food poisoning, dengue fever, influenza, AIDS.

Types of epidemics

1. Common source outbreaks

Refers to the exposure of a susceptible population or group to a common source

of the pathogen. When a single common source is involved and all persons are
exposed at the same time, then an explosive outbreak results.

2. Propagative or progressive epidemics

Involve the transfer of the pathogenic agent from one host to another. This
usually entails multiplication and excretion of an infectious agent in the host and
sometimes includes intermediate animal/human multiplication cycles in the spread of
the organism.

3. Mixed epidemics.

Involve both a single, common exposure to an infectious agent and secondary,

propagative spread to other individuals, usually by person-to-person transmission.
Examples include many food-borne pathogens (Salmonella, typhoid, hepatitis A) and
airborne organisms (Mycobacterium tuberculosis).

Epidemics, like diseases, do not occur by chance; they require a unique combination of
events, including a harmful agent coming into contact with a group of susceptible hosts in the
proper environment.

Investigation of an epidemic

The purpose of an investigation of an epidemic is to describe the outbreak and to explain

how and why the outbreak took place. There are seven basic steps in conducting an
investigation.

1. Verify the diagnosis of the disease under investigation.

 1. Check validity of the information.
2. Obtain reports of laboratory tests performed
3. Identify cases and get information from them (demographic details, clinical picture,
lab.test results, contact with ill persons, date of exposure)
4. Ensure collection of clinical specimens (feces, vomitus) and food samples (in foodborne
epidemics)

2. Establish the existence of an epidemic

1. Look for unrecognized or unreported cases. Ask physicians, hospitals, laboratories, and
friends of known cases.
2. Determine the population at risk of developing the disease. This may be a classroom,
the whole school, or the entire community.

3. Compare the incidence of disease in the population now with previous time periods,
using the case count as a numerator and the population at risk as a denominator.
Because of seasonal variations, compare the incidence with the same time period in
previous years.

3. Characterize the distribution of cases by the epidemiologic variables of person, place, and
time

1. Person

a. Name, address, age, sex, date of birth, occupation.

b. Clinical information: symptoms: date and time of onset, nature, duration. Medical
visits/hospital admissions, treatment, outcome.
c. Risk factor information: to allow the source and vehicle of epidemic to be identified.
food history, sources of food and water supply, date and time of exposure, contact
with people with similar signs and symptoms, recent group gatherings, others.

Line list for summarizing case data

________________________________________________________________________
ID Name Age Sex Date, time Major signs and symptoms Lab.
illness onset Dia Vom Fev Ano tests
_______________________________________________________________________
1 MR 34 F 5/05, 22:00 + - + + E.coli
2 ST 45 M 6/05 10:00 + - + + N.D.
3 TR 33 F 5/05 8:00 - + - - Pending
Etc.
_________________________________________________________________ _____
Dia: diarrhea, vom: vomiting; fev: fever; ano: anorexia. N.D. not identified

Analyze data: Frequency of signs and symptoms among cases

__________________________________________________
 S/S No. of cases Percentage
__________________________________________________
Diarrhea 260 88
Vomiting 122 41
Fever 116 39
Anorexia 42 14
____________________________________________________

The table will help determine whether outbreak was caused by an intoxication, an
enteric infection or a generalized illness. If the predominant symptom is vomiting
without fever and the incubation period is short (less than 8 hours), intoxication, eg.
Staphylococcus aureus is likely. Fever in the absence of vomiting and incubation period
of more than 18 hours points to an enteric infection such as Salmonella. Know the
clinical features and incubation period of foodborne pathogens.

2. Time

Epidemic curve: confirm existence of epidemic, identify mode of transmission,

determine possible period of exposure and/or incubation period of the disease,
identify source

Types of epidemic curves:

1. Common-source outbreaks, a single source of pathogen results in exposure of

persons at one point in time (point source), at several points in time (intermittent
common source) or over a continuous period (continuous common source).

An epidemic curve with a steep upslope, a more gradual down slope and with a
width approximating the average incubation period of the pathogen indicates a
point-source outbreak.

If the incubation period of the disease is known and if all of the cases occur
within one incubation period, the days can be counted backwards and the source of
infection determined.

2. Propagated epidemic is caused by the transmission of the agent from one

susceptible host to another. Could be direct person-to-person transmission, or
involve more complex cycles in which the agent must pass through a vector to be
transmitted from one human host to another, as in malaria and dengue.
New cases continue to develop beyond one incubation period.

3. Mixed epidemic involves both a common source epidemic and secondary propagated
spread to other individuals. Many foodborne pathogens (such as hepatitis A, Shigella,
and E. coli) commonly exhibit this mode of spread.
 If the incubation period of the disease is known, the curve could tell the probable
time and possible source of infection.

If the time of exposure can be determined, the incubation period of the disease
can be determined.

If the time of exposure is known, the incubation period can be used to establish a
diagnosis in foodborne outbreaks. Staphyloccocal food poisoning has an onset of 2 –
6 hours, Salmonella and Shigella in 24 – 72 hours.

3. Place

• Geographical extent of the outbreak.

• May reveal clusters or patterns that provide important clues about the cause.
• Spot maps are produced by placing a dot or other symbol on the map showing where a
case lives, works or may have been exposed. Clusters or patterns may reflect water
supplies or proximity to a restaurant or to a grocery.

On a spot map of a hospital, clustering of cases is consistent with a focal source or

person-to- person spread, while scattering of cases throughout the facility may be more
consistent with a widely disseminated vehicle or a source common to all residents.

4. Develop a hypothesis that can adequately explain the distribution of cases observed.
Summarize the data and formulate hypothesis to explain the outbreak. Address the source of
the agent, the mode and vehicle of transmission, and the specific exposure that caused the
disease. Should also be plausible, supported by the facts established during the
epidemiological, laboratory and food investigations. The hypothesis should be able to
explain most of the cases.

5. Test the hypothesis to explain the distribution of cases observed.

Analytical epidemiological studies aim to explain the specific exposure that caused
the disease. Such studies involve comparisons of the characteristics of a group of well
persons with those of ill persons in order to quantify the relationship between specific
exposures and the disease under investigation.

Two most commonly used in outbreak investigations are cohort studies and case–
control studies.

Example: a school outbreak of gastroenteritis, in which 30 cases are identified.

Interviewing all 30 cases about their food consumption shows that all ate vanilla ice cream
purchased from a street-vendor one day before illness. No other food item was consumed by
as many cases as vanilla ice cream.

Comparing the 30 cases with a group of 60 healthy students from the same school
reveals that all the healthy students also ate vanilla ice cream purchased from the same street-
vendor. Comparison of other exposures, however, reveals that most of the 30 cases had
lunch in the school canteen the day before illness while most of the healthy students did not.
This difference indicates that food from the school canteen is the more likely vehicle for the
outbreak than vanilla ice cream: the finding that all cases had eaten vanilla ice cream merely
reflects its popularity among the students.

Retrospective cohort studies

• Feasible for outbreaks in small, well-defined populations in which all exposed and all
non-exposed persons are identifiable.
• Compare the occurrence of disease among those who were exposed to a suspected risk
factor with occurrence among those who were not.
• E.g. all persons attending a wedding reception (the “cohort”) may be interviewed to
determine whether they became ill after the reception, and to identify what foods and
drinks they had consumed. After collecting information from each attendee, attack rates
for illness are calculated for those who ate a particular food and for those who did not eat
that food.

• Table. Cohort study

_____________________________________________
Exposure ill Not ill Total Attack rate
_____________________________________________
Ate food A 48 20 68 71%
Did not eat food A 2 100 102 2%
Total 50 120 170 29%
______________________________________________

Attack rate is commonly used in disease outbreak investigations and is a key

factor in the formulation of hypotheses. Number of cases in the population at risk
divided by the number of people in the population at risk.

In this example, of a total of 68 persons who ate food “A”, 48 fell ill (attack rate
48/68 or 71%). The attack rate for those who did not eat food “A” was 2/102 or 2%. Food
"A" is a likely risk factor for illness because the attack rate is high among those exposed
to food “A” (71%); the attack rate is low among those not exposed to food “A” (2%), so
the difference (risk difference) between the two attack rates is high (69%); most cases
(48/50 or 96%) were exposed to food “A”.

Relative risk (RR)

Attack rate for those who ate food “A”_____ = 71% = 35.5
Attack rate for those who did not eat food “A” 2%

A relative risk has no unit. Is a measure of the strength of association between

the exposure and the disease.
 RR = 35.5 means that persons who ate food “A” were 35.5 times more likely to
develop disease than those who did not. Statistical significance tests are used to
determine the probability that this relative risk could have occurred by chance alone.

Case - control study

There is no clearly defined “cohort” of all exposed and non-exposed persons who
can be identified or interviewed. A descriptive study has already yielded information
from cases.

The distribution of exposures among cases and a group of healthy persons

(controls) are compared with each other.

Table. Case-control study

__________________________________________
Exposure Cases Controls Total
__________________________________________
Ate food A 48 20 68
Did not eat food A 2 100 102
Total 50 120 170
Percentage
exposed 96% 17% 40%
__________________________________________

In this example, 96% of all cases had consumed food “A” compared with only
17% of the controls. This suggests that consumption of food “A” is associated with
illness in one way or another.

Attack rates (and therefore relative risk) cannot be calculated since the total
number of persons at risk is unknown. Instead, calculate odds ratio (OR) in case–control
studies. The odds ratio is calculated as the “cross-product” of a two-by-two table.

Two-by-two table from a case-control study

____________________________________________________
Cases Controls Total
___________________________________________________
Ate food A 48 20 54
Did not eat food A 2 100 21
Total 46 29 75
____________________________________________________

Calculate OR: Cross-product from a two-by-two table : the number of cases exposed (48)
times the number of controls not exposed (100) , divided by the number of controls
exposed (20) times the number of cases not exposed (2).
 Odds ratio = (48 x 100) = 120
(20 x 2)

Odds ratio of 120 for food “A” can be interpreted as: the odds of having been exposed to
the contaminated food in those who developed the disease was 120 times that of people
who did not eat food “A”. This odds ratio means that there is a very strong association
between being a case and consumption of food “A”

An important decision in the design of a case–control study is defining who

should be the controls. Controls must not have the disease in question but should
represent the population from which the cases come. In this way, controls provide the
level of background exposure that might be expected among cases. If cases have a much
higher exposure than controls, exposure may be associated with disease.

6. Formulate a conclusion

Formulate a conclusion based upon all pertinent evidence and the results of the
hypothesis testing. Conclusion explains the source of the agent, the mode and vehicle of
transmission, and the specific exposure that caused the disease.

7. Institute control measures.

Control measures should be instituted as early as possible in the outbreak

investigation. Control measures are directed at one of the six conditions or events in the
infectious disease process. The control measure selected depends upon the disease under
investigation.

Lecture series 5.

Epidemiological concept of statistical relationships

• Cause - a factor whose frequency varies with that of the health condition of interest. An
increase or decrease in the amount or frequency of the causal agent produces a parallel
increase or decrease in the frequency of the health condition.

• First step in investigating statistical relationships between two factors or events is to

determine whether any relationship or association that does exist can be expected to
occur by chance alone or whether the two factors occur together with a frequency greater
than would be expected by chance.
 • Once it has been determined that two factors are not independent, that is, that they have a
statistical significant association, the next step is to determine whether the relationship is
causal.

• Causal relationship may be of two types:

1. Direct causal relationship
One factor causes a disease with no other factor intervening.
causal factor --------- outcome
example: TB bacillus --------- TB
2. Indirect causal relationship
A third variable, an intervening variable, occupies an intermediate stage between
the cause and effect.
A --- B ----- C ---- D
A is causally related to D (A is cause, D is effect), but only through the
interposition of one or several linked factors such as B and C.
Example: Cigarette smoking (A) causes damage to respiratory epithelium (B),
B increases susceptibility to infection (C). C results in chronic bronchitis (D).

• Statistical association may also be a non-causal association, or secondary association.

This usually results from association of both categories of events with a third category.
If C is causally associated with A and B, i.e., C precedes and influences both A, B, then
A and B will necessarily be associated statistically. However, the association between A
and B is non-causal since there is no prospect of altering B by manipulating A.

Epidemiological Studies

Types of epidemiological studies

I. Descriptive
1. Case studies
2. Case series
3. Cross-sectional study

II. Analytic
 1. Observational
a. Case control study
b. Cohort study
Prospective cohort
Retrospective cohort
2. Experimental

The Epidemiological Study

Controlled Assignment Uncontrolled assignment

Experimental studies Observational studies

Community Randomized person Sampling with Sampling with

assignment assignment regard to disease regard to exposure,charac-
or effect teristic or suspected cause

Community trials Randomized Case control Cohort

clinical trials studies studies

Descriptive studies

 Characterize the disease occurrence in a population.

 Often the first step in epidemiological investigation.
 Can provide clues regarding etiology of the disease and thus, may be useful as basis for
formulating hypotheses regarding disease etiology.

Case study
- describes one case of an illness.

Case series – two or more cases of same illness.

- describe only those with the disease, will generally not be able to provide information
on whether or not the exposure is associated with the disease of interest.

Cross-sectional study

Simplest variety of descriptive or observational epidemiology that can be conducted on

representative samples of a population.
 Aims to describe the relationship between diseases (or other health-related states) and
other factors of interest as they exist in a specified population at a particular time, without regard
for what may have preceded or precipitated the health status found at the time of the study.

Example, may include questions about smoking behavior, occupational exposure to dusts
and fumes, respiratory symptoms (cough, breathlessness), and physical examinations of physical
fitness—including simple tests of lung function. Such a study would throw some light on the
relationship of both occupational exposures and smoking behavior to respiratory symptoms and
respiratory function. However, it is impossible either to establish causal relationships or to get
reliable perspectives on the natural history of respiratory disease from such a study.

Must be done on representative samples of the population if generalizations from the

findings are to have any validity. These studies gather information about the prevalence of
health-related states and conditions, but they cannot distinguish between newly occurring and
long-established conditions. All they can do is measure the frequency (prevalence) of conditions
and demonstrate associations. They cannot identify cause-and-effect relationships, though they
do identify the existence of health problems.

Also known as surveys, are a useful way to gather information on important health-
related aspects of people's knowledge, attitudes, and practices (such studies are known as "KAP"
surveys). In the area of reproductive health, such a survey might include questions such as: How
much do girls and women in their reproductive years know about pregnancy and control over
their own fertility? What are their beliefs, values, and attitudes towards making decisions about
getting pregnant and about desired family size? How do they control their own fertility? KAP
surveys are a good example of a tried and tested form of cross-sectional study. Many have been
conducted serially to measure the efficacy of family-planning programs, anti-smoking measures,
and other public health and health-promotion interventions.

Cross-sectional studies are often used as a basis for health-policy decisions, and it is
important to ensure that only current, rather than obsolete, information is used for this purpose.
When health department resources are limited, information gathered in a cross-sectional study in
the past can usually be refreshed with up-to-date facts from a small sub-sample; it would be
necessary to repeat a large cross-sectional study only if the findings from a current sub-sample
are seriously discrepant from earlier results.
Case-control study

Schema of case-control study

Study population
Classification of subjects

Cases (with Control (free

Outcome) of outcome)

Assessment of factor

Without With Without

With factor
factor factor Factor

Analysis of Data

Is an application of medical history-taking that aims to identify the cause of disease

among a group of people, or the cause-effect relationships of a condition of interest. The past
medical history, or history of exposure to a suspected risk or protective factor, of a group of
persons with the disease or condition of interest (the cases) is compared with the past history of
another group of persons (the controls) who resemble them in as many relevant respects as
possible, but who do not have the disease or condition of interest.

Statistical analysis is used to determine whether there is a stronger association of past

exposure to the suspected risk or protective factor with the condition of interest among the cases
than among the controls.

Examples: Case-control studies on the risk factors for breast cancer. Case-control studies
of smoking and lung cancer.

Useful in studying very rare conditions. During 1969 and 1970, eight cases of
adenocarcinoma of the vagina were seen in adolescent girls and young women in Boston,
Massachusetts. This was, up till then, an extremely rare, almost nonexistent condition, and it was
clear that these young women must have been exposed to some unusual cancer-causing agent.
Each of the eight cases was matched with four otherwise similar but healthy females of the same
age. Their, and their mothers', past histories of many kinds of exposure to medications, vaginal
douches, and other substances, were compared. Seven of the eight cases had a history of their
mothers having been given artificial estrogen to prevent miscarriage early in pregnancy (this had
been a popular though unproven method of preventing threatened miscarriage since the 1950s; it
has now been shown to be useless). None of the controls had a similar history. There was less
than a 1 in 100,000 likelihood of this distribution occurring by chance. Adenocarcinoma of the
vagina was caused by prenatal exposure of the developing female fetus to diethylstilbestrol, an
artificial estrogen.

The advantages of the case-control method are: (1) it is an excellent way to study rare
diseases and diseases with long latency, (2) a relatively quick answer can be obtained, (3) it is
relatively cheap, (4) it usually requires only a few cases, (5) it can often make use of existing
records, and (6) it can study several possible causes or exposures to risk simultaneously.

The disadvantages of the method are: (1) it relies on subjects' recall and/or completeness
of existing records, (2) it may be difficult or impossible to validate this information, (3) there is
incomplete allowance for extraneous factors, (4) the selection of a suitable comparison (control)
group may be difficult, (5) rates cannot be calculated, (6) the mechanism of disease cannot be
studied, and(7) a proof of causation cannot be established.

Analysis of the results of a case-control study makes use of a simple approximation,

the odds ratio. This ratio is based on the assumption that the condition under study is relatively
rare. If it is, the total number exposed to risk is close to the number of healthy persons exposed,
and the total number not exposed to risk is close to the number of healthy nonexposed persons.

Odds ratio (OR)

__________________________________
Exposure Cases Controls
__________________________________
Exposed a b
Unexposed c d
__________________________________
a+ c b+d
Odds of exposure among cases
= a/a+c divided by c/a+c = a/c

Odds of exposure among controls

= b/b+d divided by d/b + d = b/d

Odds ratio = a/c divided by b/d = a (d)/ c(d

Example of odds ratio:

Child abuse History Mental illness

+ --
__________________________________
Exposed 23 34
Unexposed 35 132
Total 58 166
___________________________________

Compute for OR =

23 (132)__ = 2.55
34(35)

Interpretation: The risk of developing mental illness is 2.6 times as much among children with
history of child abuse compared to those without such history.

Cohort Study

Schema of cohort study

Study population

Classification of subjects Exclude those with

Outcome already

Without
With factor
factor

Detection of outcome

With Without With Without

outcome outcome outcome outcome

Analysis of data

In the analytic method of epidemiological study called a cohort study, subsets of a

defined population are identified and categorized on the basis of exposure to known levels of a
risk factor that is believed to be associated with a disease outcome such as coronary heart disease
or cancer. The numbers of persons in the total population and the numbers in each subset are
known. All are followed over a period, usually years or even decades, and the disease outcomes
are recorded and counted at specified periods. These outcomes may be the incidence of
diagnosed disease, and/or deaths certified due to the disease being studied, as well as deaths due
to other causes.
 The total numbers, or the number of person-years of observation, must be large enough to
generate stable rates, so that the rates can be compared in subsets of the total population that
have been exposed to different levels of risk. Hypotheses about causes and risk factors for
disease are tested by comparing incidence and/or mortality rates of groups exposed to different
levels of risk. This is a more powerful observational method of epidemiological study than a
case-control study, but as the above account makes clear, it is a major undertaking, involving
prolonged study of very large numbers.

Cohort studies require considerable logistical support that must be maintained over a
long period, often for many years or even decades. They are also expensive and require a large,
dedicated staff. For these reasons, cohort studies are undertaken only when the investigators have
good evidence to support their working hypothesis.

The effort and expense required to conduct cohort studies have been justified by the
results of several well-known studies. One of these is the Framingham study, which began in
1948 and still continues. It is a study of samples of the population of Framingham,
Massachusetts, in which several risk factors associated with coronary heart disease, other
cardiovascular diseases, and more recently, several other chronic diseases, have been assessed.
This and several other cohort studies have clarified our understanding of the principal risk factors
for coronary heart disease, such as elevated serum lipids, high blood pressure, and cigarette
smoking. Other well-known cohort studies include the long-term follow-up of a cohort of male
British doctors who were first asked about their smoking habits in 1951. After 20 years, the death
rates from lung cancer, other respiratory system cancers, chronic obstructive lung disease, and
coronary heart disease all showed significant differences related to smoking habits among this
large cohort (Doll and Peto 1976).

Several cohort studies of cancer risks associated with exposure to ionizing radiation have
made use of existing data to shorten considerably the many years of observation that would
otherwise be required to demonstrate and measure levels of risk. This has been made possible by
the existence of good medical records of past diagnostic X-rays that exposed people to low doses
of radiation. After case-control studies had revealed evidence suggesting that the use of
diagnostic X-rays during pregnancy might increase the risk of cancer in childhood, several
cohort studies were set up to confirm or refute this evidence. MacMahon and others used the
medical records of over three quarters of a million women in New England to determine the
amount of diagnostic radiation to which they had been exposed during pregnancy, and
ascertained the incidence and mortality rates from leukemia and other cancers, including cancers
of the brain, bone, and kidney, in the first eight to ten years of their children's lives. They found a
significantly higher rate among children who had been prenatally exposed to small doses of
diagnostic X-rays, and also observed a dose-response relationship, meaning that there were
higher rates among children whose mothers had two or more X-rays than in children whose
mothers had only one X-ray. This method is known as an historical cohort study. Other historical
cohort studies have shown that repeated chest X-rays (or fluoroscopic screenings) increase the
risk of breast cancer many years later.
 The analysis of results is uses the Relative Risk (RR) or risk ratio to estimate the
magnitude of the association between the suspected risk factor and disease outcome.

_________________________________________________

Exposure Disease Total

Present Absent
___________________________________________________
Exposed a b a+b
Unexposed c d c+d
Total a+c b+d
___________________________________________________
Cumulative incidence rate in exposed: a/ a+ b
Cumulative incidence rate in unexposed: c/ c+ d
Risk ratio = Cumulative incidence rate in exposed
Cumulative incidence rate in unexposed

A study was conducted to determine the relationship between maternal smoking and low birth
weight of the offspring. A total of 1,000 pregnant women who were cigarette smokers and
another group of 2,000 women who were non-smokers were followed up until they delivered.
The birth weights of their babies were recorded. The two groups of women were comparable
with respect to age, parity, socio-economic status and availability of health facilities for prenatal
care.

Among the smokers, 60 had babies with low birth weight, that is, less than 2,250 grams, the
corresponding figure for the non-smokers was also 60.
______________________________________
Risk factor Disease outcome Total
exposure + --
(low BW) (normal BW)
_______________________________________
+ (Smokers) 60 940 1,000
- (Non-smokers) 60 1,940 2,000
Total 120 2,880 3,000
_______________________________________
Cumulative incidence rate in exposed = 60/ 1,000 = 0.06
Cumulative incidence rate in unexposed =60/2,000 = 0.03
Cumulative incidence ratio or risk ratio = 0.06/ 0.03 = 2
Means, those who smoked in pregnancy have two times likelihood in delivering LBW babies tan
those who did not smoke.
RR measures the strength of association between the suspected risk factor (maternal smoking)
and the disease outcome (low birth weight.)

Experimental Studies

• Is the strongest of all the study designs because it provides the most control over the
study situation. Researcher artificially manipulates the study factors (independent and
confounding/ extraneous variables).

• Follows the same procedure as in a cohort study, except that he chooses a study
population without or free of the factor or intervention. He then assigns the subjects into
two groups by scientific technique. He introduces the intervention to one group and
withholds it from the other.

• The randomization of the intervention equalizes the distribution of the extraneous factors.
If randomization is not done the study is only a quasi experiment. In the laboratory the
researcher can hold the extraneous factors fixed for all subjects.

Types:

1. Prophylactic trial

Evaluation of whether a treatment or procedure reduces the risk of developing the

disease. Conducted among healthy individuals who are considered at risk of the disease.
Eg. Field trial of polio vaccine

2. Therapeutic trial

Whether a certain treatment or procedure may reduce the risk of death from a particular
disease, may diminish symptoms, or may prevent recurrence of the disease. E.g. breast
cancer – radical mastectomy vs. limited resection.

3. Randomized Clinical trial

Involves the random allocation of similar persons to the treatment group and the control
group. .

Example:

A cardiovascular specialist studying the efficacy of a new anti-hypertensive drug

decided to allocate randomly his eligible hypertensive patients (who consented to
participate) to two drugs. One group would receive the experimental drug while the other
group would receive the standard regimen. The proportion of those with lowered blood
pressure from the two groups were compared.
 4. Community trial

Treatment is assigned to communities as an aggregate.

If there is an alternative between an experimental or an observational study, the

experimental study is preferred as the epidemiologist has greater control of the conditions
under which the study is carried out. Experiments however are not always feasible. For
example, consider conducting an experiment on the effects of cigarette smoking; one
would have to randomly assign persons either to a group that would be required to smoke
or to one that would not be allowed to smoke until the experiment was concluded. Such
an experiment would be neither practical nor ethical.

Example of a Cohort study

Duration of Treatment With Nonsteroidal Anti-Inflammatory Drugs and Impact on
Risk of Death and Recurrent Myocardial Infarction in Patients With Prior
Myocardial Infarction
A Nationwide Cohort Study
http://circ.ahajournals.org/content/123/20/2226.full

Background—Despite the fact that nonsteroidal anti-inflammatory drugs (NSAIDs) are

contraindicated among patients with established cardiovascular disease, many receive
NSAID treatment for a short period of time. However, little is known about the
association between NSAID treatment duration and risk of cardiovascular disease. We
therefore studied the duration of NSAID treatment and cardiovascular risk in a
nationwide cohort of patients with prior myocardial infarction (MI).

Methods and Results—Patients ≥30 years of age who were admitted with first-time MI
during 1997 to 2006 and their subsequent NSAID use were identified by individual-level
linkage of nationwide registries of hospitalization and drug dispensing from pharmacies
in Denmark. Risk of death and recurrent MI according to duration of NSAID treatment
was analyzed by multivariable time-stratified Cox proportional-hazard models and by
incidence rates per 1000 person-years. Of the 83 677 patients included, 42.3% received
NSAIDs during follow-up. There were 35 257 deaths/recurrent MIs. Overall, NSAID
treatment was significantly associated with an increased risk of death/recurrent MI
(hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.62) at the beginning of the
treatment, and the risk persisted throughout the treatment course (hazard ratio, 1.55; 95%
confidence interval, 1.46 to 1.64 after 90 days). Analyses of individual NSAIDs showed
that the traditional NSAID diclofenac was associated with the highest risk (hazard ratio,
3.26; 95% confidence interval, 2.57 to 3.86 for death/MI at day 1 to 7 of treatment).

Conclusions—Even short-term treatment with most NSAIDs was associated with

increased risk of death and recurrent MI in patients with prior MI. Neither short- nor
 long-term treatment with NSAIDs is advised in this population, and any NSAID use
should be limited from a cardiovascular safety point of view.

Example of cohort study

Cellular telephones and cancer--a nationwide cohort study in Denmark.

Source:
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
christof@cancer.dk. 2001 Feb 7;93(3):203-7.
Abstract
BACKGROUND:
Use of cellular telephones is increasing exponentially and has become part of everyday
life. Concerns about possible carcinogenic effects of radiofrequency signals have been
raised, although they are based on limited scientific evidence.
METHODS:
A retrospective cohort study of cancer incidence was conducted in Denmark of all users
of cellular telephones during the period from 1982 through 1995. Subscriber lists from
the two Danish operating companies identified 420 095 cellular telephone users. Cancer
incidence was determined by linkage with the Danish Cancer Registry. All statistical tests
are two-sided.
RESULTS:
Overall, 3391 cancers were observed with 3825 expected, yielding a significantly
decreased standardized incidence ratio (SIR) of 0.89 (95% confidence interval [CI] =
0.86 to 0.92). A substantial proportion of this decreased risk was attributed to deficits of
lung cancer and other smoking-related cancers. No excesses were observed for cancers of
the brain or nervous system (SIR = 0.95; 95% CI = 0.81 to 1.12) or of the salivary gland
(SIR = 0.72; 95% CI = 0.29 to 1.49) or for leukemia (SIR = 0.97; 95% CI = 0.78-1.21),
cancers of a priori interest. Risk for these cancers also did not vary by duration of cellular
telephone use, time since first subscription, age at first subscription, or type of cellular
telephone (analogue or digital). Analysis of brain and nervous system tumors showed no
statistically significant SIRs for any subtype or anatomic location.
CONCLUSIONS:
The results of this investigation, the first nationwide cancer incidence study of cellular
phone users, do not support the hypothesis of an association between use of these
telephones and tumors of the brain or salivary gland, leukemia, or other cancers.

Example of case-control study

Handheld cellular telephone use and risk of brain cancer.

Source
American Health Foundation, 1 Dana Rd, Valhalla, NY 10595, USA.
jmuscat2@earthlink.net
JAMA 2001 Mar 14;286(10):1293.

Abstract
CONTEXT:
A relative paucity of data exist on the possible health effects of using cellular telephones.
OBJECTIVE:
To test the hypothesis that using handheld cellular telephones is related to the risk of
primary brain cancer.
DESIGN AND SETTING:
Case-control study conducted in 5 US academic medical centers between 1994 and 1998
using a structured questionnaire.
PATIENTS:
A total of 469 men and women aged 18 to 80 years with primary brain cancer and 422
matched controls without brain cancer.
MAIN OUTCOME MEASURE:
Risk of brain cancer compared by use of handheld cellular telephones, in hours per month
and years of use.

RESULTS:

The median monthly hours of use were 2.5 for cases and 2.2 for controls. Compared with
patients who never used handheld cellular telephones, the multivariate odds ratio (OR)
associated with regular past or current use was 0.85 (95% confidence interval [CI], 0.6-
1.2). The OR for infrequent users (<0. 72 h/mo) was 1.0 (95% CI, 0.5-2.0) and for
frequent users (>10.1 h/mo) was 0.7 (95% CI, 0.3-1.4). The mean duration of use was 2.8
years for cases and 2.7 years for controls; no association with brain cancer was observed
according to duration of use (P =.54). In cases, cerebral tumors occurred more frequently
on the same side of the head where cellular telephones had been used (26 vs 15 cases; P
=.06), but in the cases with temporal lobe cancer a greater proportion of tumors occurred
in the contralateral than ipsilateral side (9 vs 5 cases; P =.33). The OR was less than 1.0
for all histologic categories of brain cancer except for uncommon neuroepitheliomatous
cancers (OR, 2.1; 95% CI, 0.9-4.7).
CONCLUSIONS:
Our data suggest that use of handheld cellular telephones is not associated with risk of
brain cancer, but further studies are needed to account for longer induction periods,
especially for slow-growing tumors with neuronal features.

End of file