Chapter 14:
Principles of Disease and
Epidemiology
Introduction
 Pathology
is the scientific study of disease.
 Etiology:
Cause of disease.
 Pathogenesis:
Studies how disease develops.
 Virulence:
A measure of pathogenicity or ability
to cause disease.
 Infection:
Invasion or colonization of the body
by pathogenic organisms.
 Disease:
Occurs when an infection results in a
change from a state of health.
Relative Virulence of Selected Pathogens
Normal Microbiota
 Animals
are generally free from microbes in utero.
 After birth, microbial populations rapidly establish
themselves in the newborn’s body.
 Vaginal lactobacilli colonize newborn’s intestine.
 Feeding and breathing introduce many more microbes.


E. coli and other bacteria colonize large intestine.
Candida albicans colonizes mucous membranes.
 Normal
Microbiota or Flora: Microorganisms that remain
throughout an individual’s life.
 Transient Microbiota: Microorganisms that are present
for a certain time period and then disappear.
 Cells in human body: 1 x 1013
Microbes associated with human body: 1 x 1014
There are ~10 microorganisms/human body cell.
Normal Microbiota of the Body
Skin Bacteria
Gum plaque
Intestinal Flora
Location of Normal Microbiota
Relationships Between the Normal
Microbiota and the Host
 Microbial
Antagonism: Normal flora inhibits
overgrowth of harmful microbes.
Mechanisms include competition for nutrients
and affecting environmental factors such as pH,
toxic substances, and oxygen availability.
 Vaginal
flora maintains pH of 3.5-4.5 which inhibits
overgrowth of Candida albicans.
 In mouth streptococci produce compounds that inhibit
growth of many other cocci.
 In intestine E. coli produce bacteriocins, which inhibit
growth of closely related bacteria.
 C. dificile is inhibited by normal intestinal flora.
Relationships Between the Normal
Microbiota and the Host
SYMBIOSIS: “Living together”. Relationship
between the host and its normal flora.
1. Commensalism: One organism benefits, the
other is not affected (+/0).
 Many
microbes live off secretions and dead cells and
do not benefit or harm host.
2. Mutualism: Both organisms benefit from living
together (+/+).
 E.
coli synthesizes vitamin K and some B vitamins.
3. Parasitism: One organism benefits, the other is
harmed (+/-).
 Most
disease causing bacteria.
Opportunistic Infections
The nature of symbiotic relationships can change.
Opportunistic Pathogens: Organisms that
normally do not cause disease in their natural
habitat in a healthy person. They may cause
disease if the host is weakened or if they enter a
different part of the body.
 Pneumocystis
carinii pneumonia in AIDS patients.
 Tooth decay and gum disease caused by mouth flora.
 Neisseria meningitidis is usually harmless in
respiratory tract, but can cause meningitis.
 E. coli can cause urinary tract infections, meningitis,
pneumonia, and abscesses.
Cooperation Among Microbes
Synergism: The effect of two microbes acting
together, is greater than the effect of either acting
alone.
 HIV
and mycoplasma infection: Cells infected with
mycoplasma and HIV die more readily than those infected
with mycoplasma alone.
 HIV and Oncogenic Viruses:


Women with HIV infections develop very aggressive cervical
cancers which are caused by papillomavirus.
Individuals with HIV and Human Herpes Virus 8 infections, are
more likely to develop Kaposi’s sarcoma.
 Oral
streptococci and pathogens that cause gingivitis and
periodontal disease. Pathogens bind to streptococci
instead of host tissue.
How Bacterial Cells Damage Host Cells
Three mechanisms:
 Direct
Damage
 Toxins*
 Hypersensitivity
Reactions
* Most bacterial damage is carried out by toxins.
1. Direct Damage



Some bacteria can induce cells to engulf them (E. coli,
Shigella, Salmonella, and Neisseria gonorrhoeae).
Microbial metabolism and multiplication kills host cells.
Other microbes enter the cell by excreting enzymes or
through their own motility.
2. Toxin Production







Toxins: Poisonous substances produced by microbes.
Frequently toxins are the main pathogenic factor.
Toxigenicity: Ability of a microbe to produce toxins.
Toxemia: Presence of toxins in the blood.
Toxin effects: May include fever, cardiovascular
problems, diarrhea, shock, destruction of red blood
cells and blood vessels, and nervous system
disruptions.
Of 220 known bacterial toxins, 40% damage
eucaryotic cell membranes.
Two types of toxins:
 Exotoxins
 Endotoxins
Exotoxins versus Endotoxins
A. Exotoxins
 Proteins:
Enzymes that carry out specific reactions.
 Soluble in body fluids, rapidly transported throughout
body in blood or lymph.
 Produced mainly by gram-positive bacteria.
 Most genes for toxins are carried on plasmids or phages.
 Produced inside bacteria and released into host tissue.
 Responsible for disease symptoms and/or death.
Cytotoxins: Kill or damage host cells.
Neurotoxins: Interfere with nerve impulses.
Enterotoxins: Affect lining of gastrointestinal tract.
 Antibodies called antitoxins provide immunity.
 Toxoids: Toxins that have been altered by heat or
chemicals. Used as vaccines for diphtheria and tetanus.
Important Exotoxins
 Diphtheria
Toxin: Corynebacterium diphtheriae when infected by a phage
carrying tox gene. Cytotoxin inhibits protein synthesis in eucaryotic cells.
Two polypeptides: A (active) and B (binding).
 Erythrogenic Toxins: Streptococcus pyogenes produces three cytotoxins
which damage blood capillaries, causing a red rash.
 Botulinum Toxins: Produced by Clostridium botulinum. Neurotoxin that
inhibits release of neurotransmitter acetylcholine and prevents
transmission of nerve impulses to muscles, causing flaccid paralysis.
Extremely potent toxins.
 Tetanus Toxin: Produced by Clostridium tetani. A neurotoxin that
blocks relaxation of skeletal muscles, causing uncontrollable muscle
spasms (lockjaw) and convulsions.
 Vibrio Enterotoxin: Produced by Vibrio cholerae. Two polypeptides: A
(active) and B (binding). The A subunit of enterotoxin causes epithelial
cells to discharge large amounts of fluids and electrolytes.
 Staphylococcal Enterotoxin: Staphylococcus aureus produces an
enterotoxin similar to cholera toxin. Other enterotoxins cause toxic shock
syndrome.
Rash of Scarlet Fever Caused by Erythrogenic
Toxins of Streptococcus pyogenes
Muscle Spasms of Tetanus are Caused
by Neurotoxin of Clostridium tetani
Neonatal Tetanus (Wrinkled brow and risus sardoni
Source: Color Guide to Infectious Diseases, 1992
Vibrio Enterotoxin Causes Profuse Watery Diarrhea
Rice-water stool of cholera. The A subunit of enterotoxin causes
epithelial cells to discharge large amounts of fluids and electrolytes.
Source: Tropical Medicine and Parasitology, 1995
Diseases Caused by Staphylococcal Toxins
Scalded Skin Syndrome
Toxic Shock Syndrom
Endotoxins
 Part
of outer membrane surrounding gram-negative
bacteria.
 Endotoxin
is lipid portion of lipopolysaccharides (LPS),
called lipid A.
 Effect
exerted when gram-negative cells die and cell
walls undergo lysis, liberating endotoxin.
 All
produce similar signs and symptoms which may
include:
 Chills,
fever, weakness, general aches, blood clotting
and tissue death, shock, diarrhea, bleeding,
inflammation, and even death. Can also induce
miscarriage.
 Fever:
Pyrogenic response is caused by endotoxins.
Endotoxins (Continued)
 Endotoxins
do not promote the formation of
effective antibodies.
 Organisms that produce endotoxins include:
Salmonella typhi
 Proteus spp.
 Pseudomonas spp.
 Neisseria spp.

 Medical
equipment that has been sterilized may
still contain endotoxins.
 Limulus
amoebocyte assay (LAL) is a test used to
detect tiny amounts of endotoxin.
Exotoxins versus Endotoxins
Etiology of Infectious Diseases
Diseases can be caused by many factors: infection,
genetics, degeneration, and others.
Koch’s Postulates
Developed by Robert Koch in 1877 to establish
cause of infectious diseases: anthrax and TB.
1. Same pathogen must be present in every case of the
disease.
2. Pathogen must be isolated from diseased host and grown
in pure culture.
3. Pathogen from pure culture must cause disease when
inoculated in healthy, susceptible laboratory animal.
4. Pathogen must be isolated from inoculated animal and
shown to be the original organism.
Koch’s Postulates for Infectious Diseases
Exceptions to Koch’s Postulates
Koch’s principles do not apply to all diseases.
1. Some microbes cannot be cultured in artificial media.



Treponema pallidum (syphillis)
Mycobacterium leprae (leprosy)
Ricketsias, chlamydias, and viruses only multiply within cells.
2. One disease may involve several different pathogens.





Diarrhea
Pneumonia
Meningitis
Peritonitis
Nephritis
3. Some pathogens may cause several different diseases.


Streptococcus pyogenes: Scarlet fever, sore throat, skin infections,
bone infections, etc.
Mycobacterium tuberculosis: Causes disease of lungs, skin, bones,
and internal organs.
Effects of Infectious Diseases
Diseases alter normal body function and/or
structure.
 Symptoms: Subjective feelings not obvious to an
observer.
Example: Pain and malaise.
 Signs: Objective changes that can be measured.
Example: Fever, redness, swelling, paralysis.
 Syndrome: A group of signs and symptoms that
are associated with a disease.
Example: AIDS (Acquired Immune Deficiency
Syndrome) is a syndrome that varies from one
individual to another.
Classifying Infectious Diseases
 Communicable
Diseases: Spread from one host to
another, directly or indirectly.
Example: Tuberculosis, herpes, flu, AIDS,
chickenpox, mumps, polio, and hepatitis.
 Contagious Diseases: Spread easily from one
person to another.
Example: Chickenpox and measles.
 Noncommunicable Diseases: Not spread from one
host to another. Caused by microbes that live
outside the body or by opportunistic pathogens
that live inside the body.
Example: Tetanus, botulism, and yeast infections.
Disease Occurrence
Disease Incidence: New cases of a disease.
Percentage of population that contracts a disease
in a given time period.
Incidence
=
Number of New Cases
No. of People at Risk
Disease Prevalence: Total number of cases.
Percentage of population that has the disease
during given time period.
Prevalence =
Number of New + Old Cases
No. of People at Risk
Incidence and Prevalence of AIDS in US Adults
Reported AIDS Cases in the United States
Frequency and Distribution of Disease Occurrence
 Sporadic
Disease: Occurs only occasionally.
Example: Polio in U.S.
 Endemic Disease: Constantly present in the population.
Example: Common cold or ear infections.
 Epidemic Disease: Many more people than expected
acquire disease in a given time period.
Example: Influenza, gonorrhea, chlamydia, and AIDS.
 Pandemic Disease: Worldwide epidemics occuring on
more than one continent.
Example: Influenza and AIDS.
Disease Occurrence
Epidemics: Higher Numbers of Cases Than Expected
Disease Duration
 Acute
Disease: Develops rapidly, but lasts a short
time.

Examples: Flu and common cold.
 Chronic
Disease: Develops more slowly, and reactions
are less severe. Tend to recur for long periods or to be
continual.

Examples: Tuberculosis, hepatitis B, and infectious
mononucleosis.
 Subacute
Disease: Intermediate between acute and
chronic.

Examples: Subacute bacterial endocarditis (streptococci).
 Latent
Disease: Causative agent remains inactive for a
time, but then becomes active and produces disease
symptoms.

Examples: Shingles, genital and oral herpes, AIDS.
Host Involvement
 Local
Infection: Microbes are limited to small
area of body.
Examples: Boils, abscesses, and acne.
 Systemic (Generalized) Infection: Microbes are
spread throughout body by blood or lymph.
Examples: Measles, AIDS.
 Bacteremia:
Presence of bacteria in the blood.
 Septicemia: Bacteria multiply in blood.
 Toxemia: Presence of toxins in blood.
 Viremia: Presence of viruses in blood.
 Focal
Infection: Starts as a local infection and
spread to other parts of body.
Examples: From teeth, tonsils, and appendix.
Host Resistance Determines Extent of Infection
 Primary
Infection: Acute infection that causes
initial illness.
Example: Common cold
 Secondary Infection: Caused by opportunistic
pathogen after primary infection has weakened host
immune system.
Example: Pneumonia or bronchitis may develop
after the common cold.
 Subclinical Infection: Does not cause any noticeable
illness in host.
Example: Over 90% of polio infections are
asymptomatic.
Spread of Infection
Reservoirs of Infection
 Human
Reservoirs: Infected individuals who may
or may not present disease. Carriers are infected
individuals without any signs or symptoms of
disease (AIDS, polio, gonorrhea).
 Animal Reservoirs: Zoonoses are diseases that
occur primarily in wild and domestic animals.
About 150 different zoonoses are known (rabies,
anthrax, and Lyme disease).
 Nonliving Reservoirs: Two major sources are soil
and water.
 Soil:
Clostridium tetani and botulinum.
 Water: Vibrio cholerae and Salmonella typhi.
Transmission of Disease
I. Contact Transmission: Spread by direct contact,
indirect contact, or droplet transmission.
A. Direct Contact Transmission: Person-to-person
transmission. No intermediate object is involved.
Examples: Touching, kissing, sexual intercourse.
B. Indirect Contact Transmission: Agent is transferred
via a nonliving object (fomite).
Examples: Towels, eating utensils, thermometers,
stethoscopes, bedding, clothes, money, and syringes.
C. Droplet Transmission: Microbes are spread in mucus
droplets that travel short distances (less than 1 meter).
Examples: Sneezing, coughing, talking, and laughing.
Transmission of Microbial Disease
Direct Contact
Vector Transmission
Droplet Transmission
Vehicle Transmission
Transmission of Disease (Continued)
II. Vehicle Transmission: Transmission of disease
via medium such as water, food, air, blood, body
fluids, and intravenous fluids.
 Waterborne
Transmission: Usually caused by water
contaminated with sewage.
 Airborne Transmission: Spread of agents by droplets
in dust that travel more than 1 m to host.
III. Vectors: Animals that carry disease from one
host to another. Arthropods (insects) are most
important animal vectors.
 Mechanical
Transmission: Passive transport of
pathogens on insect’s body.
 Biological Transmission: Pathogen spends part of its
life cycle in the vector.
Portals of Exit
Site at which microbes leave body. Most common
exit portals are respiratory and gastrointestinal
tracts.
 Respiratory Tract: Exit in discharges (mucus
droplets) from nose and mouth. Transmission by
coughing, sneezing, spitting, etc.
 Examples:
Tuberculosis, influenza, pneumonia,
common cold, measles, mumps, scarlet fever, and
meningococcal meningitis.
 Gastrointestinal
 Feces:
Tract: Exit in feces or saliva.
Amoebas, poliovirus, cholera, typhoid fever,
salmonella, shigella, and many helminths.
 Saliva: Rabies virus, herpes simplex 1.
Portals of Exit (Continued)
 Urogenital
Tract: Exit in secretions or urine.
 Penis
and vagina: Sexually transmitted diseases.
Chlamydia, herpes simplex 2, HIV, gonorrhea, and
syphilis.
 Urine: Brucellosis and typhoid fever.
 Skin
and Wound Infections: Spread through
direct contact or through fomites.
 Example:
S. aureus, P. aeruginosa, scabies,
ringworm.
 Blood:
Transmission through insects, needles,
and syringes.
 Insects:
Malaria, yellow fever, and Lyme disease.
 Needles: AIDS and hepatitis B.
Nosocomial (Hospital Acquired) Infections
 “Nosocomial”
Greek word for hospital.
 Infections acquired at a health care facility.
 According to Center for Disease Control (CDC), 515% of all hospital patients acquire N.I.s.
 At least 100,000 deaths in US from N.I.s every year.
 Predisposing Factors:
 Wide
variety of microbes in hospital environment
 Weakened or immunocompromised patients
 Chain of transmission: Mainly through direct or
indirect contact.
•
•
•
•
From health care workers to patient
From patient to patient
Fomites: Catheters, needles, dressings, beds, wheelchairs
Airborne transmission
Factors Contributing to Nosocomial Infections
Important Nosocomial Pathogens
 Normal
microbiota: Many are opportunistic
pathogens
 Antibiotic resistance: Very high due to the use of
antimicrobials in health care facilities.
 Principle microorganisms: Used to be grampositive microbes. Today most are gram-negative
bacteria.
 Enterobacteria:
Over 40% of all infections. E. coli,
Klebsiella spp., Proteus spp., Enterobacter spp., and
Serratia marcescens.
 Staphylococcus aureus (11%)
 Fungi: (10%) C. albicans and others
 Enterococcus (10%)
 Pseudomonas aeruginosa (9%)
Principal Kinds of Nosocomial Infections
35
34
Percentage
30
25
22
20
17
15
13
14
10
5
0
Urinary Tract Surgical Site
Lower
Respiratory
Bacteremia
Other, skin
Control of Nosocomial Infections
 Aseptic
techniques to avoid contamination
 Careful handling and disposal of contaminated
material
 Frequent and adequate hand washing
 Proper infection control training of staff
 Isolation wards and rooms
 Avoid unnecessary antibiotic prescriptions
 Avoid unnecessary invasive procedures
 Regular disinfection of respirators and
humidifiers and maintenance of autoclaves
 Use disposable and/or sterile supplies
 Infection control committee
Control of Nosocomial Infections
Predisposing Factors for Disease
Factors that make an individual more susceptible
to a given disease.
 Gender
 Genetic factors
 Climate and weather
 Nutrition
 Fatigue/Stress
 Occupation
 Environment
 Lifestyle
 Age
 Other illness
Development of an Infectious Disease
1. Incubation Period: Time between initial
infection and appearance of signs and symptoms
2. Prodromal Period: Early, mild symptoms of
disease.
3. Illness Period: Disease is most acute. Overt
signs and symptoms. Patient immune system
actively fights off infection. If not successful may
die at this stage.
4. Decline Period: Signs and symptoms subside.
Patient is vulnerable to secondary infections.
5. Convalescence Period: Recovery. Body returns
to predisease state.
The Stages of an Infectious Disease
Epidemiology
 Science
that studies when and where diseases
occur and how they are transmitted in a
population.
 Modern epidemiology began in 1854 during a
cholera epidemic in London.
 Epidemiologists collect information to determine:
 Etiology:
Cause of disease (pathogen).
 Predisposing factors: Age, sex, lifestyle, etc.
 Incidence: Number of individuals acquiring disease in
a given time period.
 Prevalence: Number of individuals with disease in a
given time period.
 Transmission
 Public Health Policy and Prevention
Epidemiological Data from 1854
London Cholera Epidemic
Epidemiological Data
Epidemiological Data
Types of Epidemiological Investigation
 Descriptive
Epidemiology: Retrospective studies that
collect data on diseases occurrence.



Collect data on location and time of disease and on patients (age,
gender, occupation, health history, socioeconomic groups, etc).
Try to identify the “index case’ or first case for a disease in a given
area or population.
Examples: Initial studies on cholera and toxic shock syndrome
outbreaks.
 Analytical
Epidemiology: Analyzes a disease to determine
its probable cause, means of transmission, and prevention.
May be used when Koch’s postulates cannot be applied.


Case control method: Look for factors that precede disease.
Compare sick individuals to healthy individuals.
Cohort method: Study two populations, one that has been exposed
to a certain risk factor (e.g.: blood transfusion or sexual contact) .
Control group is not exposed to risk factor.
 Experimental
Epidemiology: Test hypotheses on disease
causes. Can also test drugs or vaccines on susceptible
populations.
Case Reporting
Procedure that requires health workers to report
specified diseases to government agencies.
Partial list of 63 reportable diseases in the U.S. (2005):
 AIDS
 Botulism
 Chlamydia
(genital)
 Diphtheria
 Gonorrhea
 Hepatitis
A, B, and C
 Lyme Disease
 Measles
 Plague
 Rubella
 Tetanus
 Varicella (deaths only)
Anthrax
Brucellosis
Cholera
Enterohemorrhagic E. coli
Hansen’s Disease (Leprosy)
HIV infection
Malaria
Mumps
Rabies
Syphilis
Tuberculosis
Yellow fever
Case Reporting
Center for Disease Prevention and
Control (CDC)
 Central
source of epidemiological information in
U.S.
 Branch of U.S. Public Health Service
 Located in Atlanta, Georgia
 Weekly publication “Morbidity and Mortality
Report” (MMWR)
 Morbidity:
Number of specific notifiable diseases.
 Mortality: Number of deaths from diseases.
 Reports on disease outbreaks
 Special interest case histories
 Summaries on status of diseases
 Recommendations for diagnosis, immunization, and
treatment.