AMB 462 Introduction

Epidemiology is the study of the determinants, distribution, and frequency of disease (who gets the
disease and why) OR

The study of the distribution and determinants of health-related states or events in specified populations,
and the application of this study to control of health problems

Epidemiology covers all major health problems in the community including:

i. Communicable diseases
ii. Chronic degenerative, metabolic, neoplastic diseases
iii. Nutritional deficiencies
iv. Occupational health and injuries
v. Mental and behavioral disorders
vi. Population issues and demographic trends

USES OF EPIDEMIOLOGY

1. It is used to determine the health of a population by the design, conduct and interpretation of studies.
2. To determine, describe, and report on the natural course of disease, disability, injury, and death
3. Epidemiology attempts to identify causative agents, the factors in the web of causation, the
populations at highest risk, environmental and other determinants.
4. To aid in the planning and development of health services and programs
5. To provide administrative and planning data and supply tools for evaluating health programmes.
6. It provides a foundation for public policy and for making regulatory decisions especially those
relating to environmental problems.

Two Broad Types of Epidemiology

Descriptive epidemiology: examining the distribution of disease in a population, and observing the basic
features of its distribution

Analytic epidemiology: investigating a hypothesis about the cause of disease by studying how exposures
relate to disease

Descriptive epidemiology
The 5W’s of descriptive epidemiology:
• What = health issue of concern
• Who = person
• Where = place
• When = time
• Why/how = causes, risk factors, modes of transmission
Epidemiologists tend to use synonyms for the five W’s listed above: case definition, person, place, time,
and causes/risk factors/modes of transmission. Descriptive epidemiology covers time, place, and person.
Time
The occurrence of disease changes over time. Seasons also affect disease occurrence (seasonal/annual
occurrence or trend). For such diseases that occur seasonally, health officials can anticipate their occurrence
and implement control and prevention measures, such as an influenza vaccination campaign or mosquito
spraying.
Cyclic occurrence/trend- this takes about 2-3 years cycle to occur e.g. rabies
Secular occurrence/trend- this takes a cycle of about 5years and above to occur e.g. yellow fever
Sporadic occurrence- can occur anytime e.g. salmonellosis, hepatitis B
Place
Characterization by place refers not only to place of residence but to any geographic location relevant to
disease occurrence. Such locations include place of diagnosis or report, birthplace, site of employment,
school district, hospital unit, or recent travel destinations.
For example, is a community at increased risk because of-
1. Characteristics of the people in the community such as genetic susceptibility, lack of immunity,
risky behaviors, or exposure to local toxins or contaminated food? OR
2. Characteristics of the causative agent such as a particularly virulent strain, hospitable breeding sites,
or availability of the vector that transmits the organism to humans?
3. Or characteristics of the environment that brings the agent and the host together, such as crowding
in urban areas that increases the risk of disease transmission from person to person, or more homes
being built in wooded areas close to deer that carry ticks infected with the organism that causes
Lyme disease?
Person
Person characteristics include inherent characteristics e.g. age, sex, ethnicity/race/breed; biological
characteristics e.g. immune status; acquired characteristics e.g. marital status; activities e.g. occupation,
leisure activities, use of medications/tobacco/drugs; and living conditions e.g. socioeconomic status, access
to medical care.
Age- most health-related event varies with age. A number of factors that also vary with age include:
susceptibility, opportunity for exposure, latency or incubation period of the disease, and physiologic
response. Poliomyelitis, and measles occur in children, hypertension and stroke occur in old age and STDs
occur mostly in reproductive age. When analyzing data by age, epidemiologists try to use age groups that
are narrow enough to detect any age-related patterns that may be present in the data.
Sex/gender- some diseases occur more in one gender than the other e.g. breast cancer in females and
prostate cancer in males. For some diseases, this sex-related difference is because of genetic, hormonal,
anatomic, or other inherent differences between the sexes. These inherent differences affect susceptibility
or physiologic responses. For example, premenopausal women have a lower risk of heart disease than men
of the same age. This difference has been attributed to higher estrogen levels in women. On the other hand,
the sex-related differences in the occurrence of many diseases reflect differences in opportunity or levels
of exposure. For example, lung cancer used to be higher in males than females because there was higher
prevalence of smoking among males than females.
Ethnicity/race/breed- Differences in racial, ethnic, or other group variables may reflect differences in
susceptibility or exposure, or differences in other factors that influence the risk of disease, such as
socioeconomic status and access to health care.
Socioeconomic status- Socioeconomic status is difficult to quantify. It is made up of many variables such
as occupation, family income, educational achievement or census track, living conditions, and social
standing. Nevertheless, epidemiologists commonly use occupation, family income, and educational
achievement, while recognizing that these variables do not measure socioeconomic status precisely. The
frequency of many adverse health conditions increases with decreasing socioeconomic status. For example,
tuberculosis is more common among persons in lower socioeconomic strata. Infant mortality and time lost
from work due to disability are both associated with lower income.
A few adverse health conditions occur more frequently among persons of higher socioeconomic status.
Gout was known as the “disease of kings” because of its association with consumption of rich foods. Other
conditions associated with higher socioeconomic status include breast cancer, Kawasaki syndrome, chronic
fatigue syndrome, and tennis elbow.
Analytic epidemiology
Descriptive epidemiology can identify patterns among cases and in populations by time, place and person.
From these observations, epidemiologists develop hypotheses about the causes of these patterns and about
the factors that increase risk of disease. In other words, epidemiologists can use descriptive epidemiology
to generate hypotheses, but only rarely to test those hypotheses. For that, epidemiologists must turn to
analytic epidemiology. The key feature of analytic epidemiology is a comparison group. Analytic
epidemiology is concerned with the search for causes and effects, or the why and the how. Epidemiologists
use analytic epidemiology to quantify the association between exposures and outcomes and to test
hypotheses about causal relationships.

SPECTRUM OF INFECTION
Spectrum of infections refers to the complete range of manifestations of a disease. Many, if not most,
diseases have a characteristic natural history, although the time frame and specific manifestations of disease
may vary from individual to individual and are influenced by preventive and therapeutic measures.

Figure 1: Illustration of the Spectrum of infections

The onset of symptoms marks the transition from subclinical to clinical disease. Most diagnosis is made
during the stage of clinical disease. In some people, however, the disease process may never progress to
clinically apparent illness. In others, the disease process may result in illness that ranges from mild to severe
or fatal. This range is called the spectrum of infection. Ultimately, the disease process ends either in
recovery, disability or death. The following are considered in the spectrum of infection/disease.
For an infectious agent,
Infectivity is the ability of a pathogen to establish an infection.
Pathogenicity is the ability of an organism to cause disease.
Virulence refers to the proportion of clinically apparent cases that are severe or fatal.
Cholera is highly pathogenic but less virulent whereas rabies is less pathogenic but more virulent. Spectrum
of infection progresses from susceptibility to virulence.
Susceptibility is a property of the host (proneness to a disease). An effectively immunized person against
Diphtheria, Pertusis and Tetanus (DPT) is not susceptible to these diseases for at least one year.
Infectiousness is the property of the agent that causes infection. Measles virus is highly infectious for a
susceptible host but HIV is not. At the end of the spectrum is mortality, which is the ultimate for virulence.
Mortality can be measured per 1000 population or as percent affected. The following indicators can be
calculated to delineate the spectrum of a disease:
• Infectivity = no. of subjects infected/no of subjects exposed x 100
• Pathogenicity= no. of subjects manifesting the disease/no of subjects infected x 100
• Virulence = no. of subjects with serious disease (including mortality)/no of subjects with the
disease x 100
Disease spectrum is likely to be very different during the times of epidemics than in normal times.
Epidemics is said to have occurred when the incidence is clearly in excess of the usual rate. Another related
concept is transmissibility. If an infectious person is able to infect at least one person on average during
the entire period of infectivity, then the infection will sustain or increase, and it is called Reproductive
rate of infection.
Many additional cases may be too early to diagnose or may never progress to the clinical stage.
Unfortunately, persons with apparent or undiagnosed infections may nonetheless be able to transmit
infection to others. Such persons who are infectious but have subclinical disease are called Carriers.
Stages in Disease Spectrum
1. Stage of Susceptibility: At this stage the disease has not developed but the groundwork has been laid by
the presence of factors that favour its occurrence. Factors whose presence are associated with the increased
probability of the disease developing later are called risk factors. Risk factors are immutable or susceptible
to change. Neither will all individuals with risk factor necessarily develop the disease nor will the absence
of risk factor ensure the absence of disease. Our inability to identify all the risk factors contributing to risk
of disease limits our ability to predict its occurrence.
2. Stage of Pre-Symptomatic Disease: At this stage there is no manifestation of disease but, usually through
the interaction of factors, pathogenic changes have started to occur.
3. Stage of Clinical Disease: By this stage sufficient end-organ changes have occurred so that there are
recognizable signs or symptoms of disease. Depending on a specific disease, these are classified on
morphological, functional or therapeutic considerations.
4. Stage of Disability: There are a number of conditions which give rise to a residual defect of
short or long duration, leaving the person disabled to a greater or a lesser extent.
HERD IMMUNITY
Herd immunity also called herd effect, community immunity, population immunity or social immunity, is
a form of immunity that occurs when the vaccination of a significant portion of a population provides a
measure of protection for individuals who have not developed immunity. This occurs because there are few
susceptible people left to infect. This can effectively stop the spread of disease in the community. It is
particularly crucial for protecting people who cannot be vaccinated.
The mechanism of herd immunity is that individuals who are immune to a disease act as a barrier in the
spread of disease, slowing or preventing the transmission of disease to others. An individual's immunity
can be acquired via a natural infection or through artificial means, such as vaccination. When a critical
proportion of the population becomes immune, called the herd immunity threshold (HIT) or herd immunity
level (HIL), the disease may no longer persist in the population, ceasing to be endemic. The proportion of
the population which must be immunized in order to achieve herd immunity varies for each disease but the
underlying idea is simple: once enough are protected, they help to protect vulnerable members of their
communities by reducing the spread of the disease. It is particularly crucial for protecting people who
cannot be vaccinated.
The principle of community immunity applies to control of a variety of contagious diseases, including
influenza, measles, mumps, rotavirus and pneumococcal disease. It is important to note that herd immunity
is only applicable to contagious diseases.
However, when immunization rates fall, herd immunity can break down leading to an increase in the
number of new cases. Unlike vaccination, herd immunity does not give a high level of individual protection,
and so it is not a good alternative to getting vaccinated.
Herd immunity does not protect against all vaccine-preventable diseases. The best example of this is tetanus
which is infectious but not contagious i.e. it is caught from bacteria in the environment and not from infected
persons. No matter how many people around you are vaccinated against tetanus, it will not protect you from
tetanus.
People who depend on herd immunity for protection are vulnerable to the disease but are not safe to receive
vaccination against them, these group of people include:
• People without a fully-working immune system. Individuals who possess an immunodeficiency
from HIV/AIDS, lymphoma, leukemia, a bone marrow cancer, an impaired spleen, chemotherapy,
or radiotherapy may have lost any immunity that they previously had and vaccines may not be of
any use for them because of their immunodeficiency
• Newborn babies who are too young to be vaccinated. Newborn infants are too young to receive
many vaccines, either for safety reasons or because passive immunity renders the vaccine
ineffective.
• Elderly people
• Many of those who are very ill in hospital
• Pregnant women.
Vaccines are typically imperfect as some individuals' immune systems may not generate an adequate
immune response to vaccines to confer long-term immunity, so a portion of those who are vaccinated may
lack immunity. Lastly, vaccine contraindications for specific populations may prevent individuals in these
populations from becoming immune.
Effects of Herd Immunity
i. It protects those who do not have immunity against diseases. High levels of immunity in one
age group can create herd immunity for other age groups. Vaccinating adults against Pertussis
reduces Pertussis incidence in infants too young to be vaccinated, who are at the greatest risk
of complications from the disease.
 ii. Herd immunity itself acts as an evolutionary pressure on certain viruses, influencing viral
evolution by encouraging the production of novel strains, in this case referred to as escape
mutants that are able to escape from herd immunity and spread more easily.
iii. Serotype replacement, or serotype shifting, may occur if the prevalence of a specific serotype
declines due to high levels of immunity, allowing other serotypes to replace it.
iv. Herd immunity results in eradication of diseases. If herd immunity has been established and
maintained in a population for a sufficient time, the disease is inevitably eliminated i.e. no more
endemic transmissions occurs.
v. Herd immunity is vulnerable to the free rider problem. Individuals who lack immunity,
primarily those who choose not to vaccinate, free ride off, the herd immunity created by those
who are immune. As the number of free riders in a population increases, outbreaks of
preventable diseases become more common and more severe.
Herd Immunity Threshold: The percentage of immune individuals needed to achieve herd immunity
varies by disease and R₀. To set a threshold, epidemiologists—experts in infectious disease transmission—
use a value called "basic reproduction number," often referred to as "R0." This number represents how
many people in an unprotected population one infected person could pass the disease along to. The higher
this number is, the higher the immunity threshold must be to protect the community. Because measles is
extremely contagious and can spread through the air, for example, the immunity threshold needed to protect
a community is high, at 95%.
Diseases like polio, which are a little less contagious, have a lower threshold—80% to 85% in the case of
polio. The general concept of an immunity threshold seems simple, but the factors involved in calculating
a specific threshold are complex. These factors include how effective the vaccine for a given disease is,
how long-lasting immunity is from both vaccination and infection, and which populations form critical
links in transmission of the disease. The collective differences in these factors result in different thresholds
for different diseases (Fig. 2), with a significant factor being R0.

Figure 2: Some diseases and their herd immunity threshold

LATENCY OF INFECTIONS
Latency in infections refers to a period when a pathogen is present in the host but remains dormant or
inactive, causing no apparent symptoms or a phase in the infection cycle where the pathogen is present but
inactive. During latency, the pathogen can evade the host's immune system and reactivate under certain
conditions, leading to disease recurrence.
Types of Latent Infections
• Viral Latency: Common in herpesviruses (e.g., HSV, Varicella-Zooster Virus), HIV, and hepatitis
B.
• Bacterial Latency: Seen in tuberculosis (Mycobacterium tuberculosis) and syphilis (Treponema
pallidum).
 • Parasitic Latency: Observed in malaria (Plasmodium spp.) and toxoplasmosis (Toxoplasma
gondii).
Mechanisms of Latency
Viral Latency
• Integration into Host Genome: Some viruses integrate their DNA into the host genome (e.g.,
HIV, herpesviruses).
• Episomal Maintenance: Viral genomes persist as episomes in the host cell nucleus without
integrating into the DNA (e.g., Epstein-Barr virus).
• Immune Evasion: Viruses reduce expression of antigens and modulate host immune responses to
avoid detection.
Bacterial Latency
• Intracellular Survival: Bacteria like Mycobacterium tuberculosis can survive within host
macrophages in a dormant state.
• Biofilm Formation: Some bacteria form biofilms, which protect them from the immune system
and antibiotics (e.g., Pseudomonas aeruginosa in chronic infections).
Parasitic Latency
• Dormant Stages: Parasites may form cysts or dormant stages that persist in host tissues (e.g.,
Toxoplasma gondii bradyzoites).
• Antigenic Variation: Parasites alter their surface proteins to evade the immune system (e.g.,
Plasmodium spp. causing malaria).
A case study of Latency using Varicella-Zooster Virus infection
Chickenpox is caused by the varicella-zoster virus (VZV), which belongs to the herpesvirus family. After
the primary disease that is characterized with fever, malaise, and itchy rash that progresses from macules
to papules to vesicles and then crusts resoles, VZV migrates from the skin lesions via sensory nerve fibers
to the dorsal root ganglia, where it establishes a lifelong latent infection. During latency, the virus remains
dormant within the sensory neurons and does not cause symptoms. Reactivation (now as Shingles or Herpes
Zoster) occurs due to various factors, such as aging, immunosuppression, stress, and other illnesses.
Reactivation leads to shingles, characterized by a painful, localized vesicular rash along the dermatome of
the affected nerve. Some individuals may develop Postherpetic Neuralgia (PHN), a chronic pain condition
that persists even after the shingles rash resolves.
Varicella-zoster virus expresses a limited set of viral genes during latency, which helps maintain the
dormant state and evade the host immune system. Host factors, including immune surveillance and neuronal
microenvironment, also play crucial roles in maintaining latency. The exact mechanisms are not fully
understood, but it involves changes in the neuronal environment, decreased immune function, and possibly
the activation of certain viral genes.
Factors Influencing Latency
Host Factors
• Immune Status: Immunocompromised individuals are more likely to harbor latent infections.
• Genetic Factors: Certain genetic predispositions can influence latency and reactivation.
• Age: Latent infections can be more prevalent or severe in elderly individuals.
Pathogen Factors
• Virulence Factors: Specific virulence factors enable pathogens to enter latency.
• Mutation Rate: High mutation rates can facilitate immune evasion and latency (e.g., HIV).
Environmental Factors
• Stress: Physical or psychological stress can trigger reactivation of latent infections.
• Co-infections: Other infections can compromise the immune system, leading to reactivation.
• Drugs: Immunosuppressive drugs can increase the risk of reactivation.
Prevention and Management
• Vaccination: Preventive vaccines can reduce the risk of primary infection and latency (e.g., VZV
vaccine).
• Screening: Regular screening in high-risk populations to detect and manage latent infections.
• Public Health Strategies: Addressing social determinants of health to reduce the risk of latent
infections and reactivation.

While latent or latency period may be synonymous, a distinction is sometimes made between incubation
period and latent period. Depending on the disease, the person may or may not be contagious during the
incubation period. The incubation period is the time from acquiring the infection to the first symptoms of
illness. The incubation period varies from person to person within a range that is characteristic for the
disease. It may be shorter with a higher infecting dose.
Infection
The infectious period is the time during which someone with an infection can transmit the infection to
someone else. The degree of infectiousness varies through the infectious period.
An Infection is the invasion and multiplication of microorganisms in body tissues, especially that causing
local cellular injury due to competitive metabolism, toxins, intracellular replication or antigen response.
There are different types of infection and they include:
Acute infection: This is an infection that is for a short duration of the order of several days.
Airborne infection: it is an infection caused by inhalation of organisms suspended in air on water droplets
or dust particles.
Droplet infection: This is infection caused by inhalation of respiratory pathogens suspended on liquid
particles exhaled by an animal that is already infected.
Dust-borne infection: It is an infection that is caused by inhalation of pathogens that have become affixed
to particles of dust.
Arrested infection: It is an infection that has been restrained in its development by a capsule or adhesion
but still containing infective material.
Secondary infection: It is an infection by a pathogen following an infection by an infection by a pathogen
of another kind.
Chronic infection: it is infection that is for a long duration of the order of weeks, months, or years.
Cross infection: This is infection transmitted between patients infected with different pathogenic
microorganisms.
Endogenous infection: It is an infection that is due to reactivation of organisms present in a dormant focus,
example is Tuberculosis.
Exogenous infection: It is an infection caused by organisms not normally present in the body but which
have gained entrance from the environment.
Local infection: It is an infection that has common syndrome of varying degree peculiar to a site or organ
infected in the host.
Opportunistic infection: it is any infection caused by a microorganism that does not normally cause
disease in humans; occurs in persons with abnormally functioning immune systems.
Super-infection: It is an infection that occurs while you are being treated for another infection.
Supra-infection: This is a secondary infection caused by an opportunistic infection.
Mixed infection: It is an infection with more than one kind of organism at the same time.
Nosocomial infection: This is an infection pertaining to or acquired in hospital.
Patent infection: It is an infection in which the infectious agent can be demonstrated in discharges of the
patient.
Persistent infection: It is an infection in which there may be long lasting or long-long latent infections with
asymptomatic periods and recurring acute episodes of clinical disease.
Pyogenic infection: It is an infection by pus-producing organisms.
Subclinical infection: It is an infection associated with no detectable signs but caused by microorganisms
capable of producing easily recognizable diseases.
Systemic infection: It is an infection that is wide-spread throughout the body and must be assumed to be
in all organs
Terminal infection: It is an acute infection occurring near the end of a disease and often causing death.
MULTIFACTORIAL SYSTEMS IN EPIDEMICS
One important use of epidemiology is to identify the factors that place some members at greater risk than
others. A number of models of disease causation have been proposed. Among the simplest of these is the
epidemiologic triad or triangle, the traditional model for infectious disease. The triad consists of an external
agent, a susceptible host, and an environment that brings the host and agent together.

Figure 3: Epidemiological Triad/Triangle of diseases

In this model, disease results from the interaction between the agent and the susceptible host in an
environment that supports transmission of the agent from a source to that host. Agent, host, and
environmental factors interrelate in a variety of complex ways to produce disease. Different diseases require
different balances and interactions of these three components.
The Casual Pie
While the epidemiologic triad serves as a useful model for many diseases, it has proven inadequate for
cardiovascular disease, cancer, and other diseases that appear to have multiple contributing causes without
a single necessary one. Because the agent-host-environment model did not work well for many non-
infectious diseases, several other models that attempt to account for the multifactorial nature of causation
have been proposed. One such model was proposed by Rothman in 1976, and has come to be known as the
Causal Pies. An individual factor that contributes to cause disease is shown as a piece of a pie. After all
the pieces of a pie fall into place, the pie is complete — and disease occurs. The individual factors are called
component causes. The complete pie, which might be considered a causal pathway, is called a sufficient
cause. A disease may have more than one sufficient cause, with each sufficient cause being composed of
several component causes that may or may not overlap. A component that appears in every pie or pathway
is called a necessary cause, because without it, disease does not occur.

Figure 4: An illustration of a Disease Casual Pie

CHAIN OF INFECTION
The traditional epidemiologic triad model holds that infectious diseases result from the interaction of agent,
host, and environment. More specifically, transmission occurs when the etiological agent leaves its
reservoir or host through a portal of exit, is conveyed by some mode of transmission, and enters through an
appropriate portal of entry to infect a susceptible host. This sequence is sometimes called the chain of
infection.
Etiologic Agents
There are seven categories of biological agents that can cause infectious diseases. Each has its own
particular characteristics. The types of agents are:
• Metazoa
• Protozoa
• Bacteria
• Fungi
• Rickettsia
• Viruses
• Prions
Reservoir
The reservoir of an infectious agent is the habitat in which the agent normally lives, grows, and multiplies.
Reservoirs include humans, animals, and the environment. The reservoir may or may not be the source from
which an agent is transferred to a host. For example, the reservoir of Clostridium botulinum is soil, but the
source of most botulism infections is improperly canned food containing C. botulinum spores. Many
common infectious diseases have human reservoirs. Human reservoirs may or may not show the effects of
illness. Carriers commonly transmit disease because they do not realize they are infected, and consequently
take no special precautions to prevent transmission.
Humans are also subject to diseases that have animal reservoirs. Many of these diseases are transmitted
from animal to animal, with humans as incidental hosts. Plants, soil, and water in the environment are also
reservoirs for some infectious agents. Many fungal agents, such as those that cause histoplasmosis, live and
multiply in the soil. Outbreaks of Legionnaires disease are often traced to water supplies in cooling towers
and evaporative condensers, reservoirs for the causative organism Legionella pneumophila.
Portal of Exit
Portal of exit is the path by which a pathogen leaves its host. The portal of exit usually corresponds to the
site where the pathogen is localized. For example, influenza viruses and Mycobacterium tuberculosis exit
the respiratory tract, cholera vibrios in feces etc. Some bloodborne agents can exit by crossing the placenta
from mother to fetus (rubella, syphilis, toxoplasmosis), while others exit through cuts or needles in the skin
(hepatitis B) or blood-sucking arthropods (malaria).
Mode of Transmission
An infectious agent may be transmitted from its natural reservoir to a susceptible host in different ways.
Mode of transmission is classified into two namely: contact, vehicle and vector-borne modes of
transmission.
Portal of Entry
The portal of entry refers to the manner in which a pathogen enters a susceptible host. The portal of entry
must provide access to tissues in which the pathogen can multiply, or a toxin can act. Often, infectious
agents use the same portal to enter a new host that they used to exit the source host.
For example, influenza virus exits the respiratory tract of the source host and enters the respiratory tract
of the new host. In contrast, many pathogens that cause gastroenteritis follow a so-called “fecal-oral” route
because they exit the source host in feces, are carried on inadequately washed hands to a vehicle such as
food, water, or utensil, and enter a new host through the mouth. Other portals of entry include the skin
(hookworm), mucous membranes (syphilis), and blood (hepatitis B, human immunodeficiency virus).
Susceptible Host
Susceptibility of a host depends on genetic or constitutional factors, specific immunity, and nonspecific
factors that affect an individual's ability to resist infection or to limit pathogenicity. An individual's genetic
makeup may either increase or decrease susceptibility. For example, persons with sickle cell trait seem to
be at least partially protected from a particular type of malaria. Factors that may increase susceptibility to
infection by disrupting host defenses include malnutrition, alcoholism, and disease or therapy that impairs
the nonspecific immune response.

Figure 5: The Chain of infection