Microbe-Human Interactions:
Contact, Infection and Disease
Host-Microbe Relationships
• Host
• Any organism that harbors another organism or particle (virus, prion)
 Symbiosis-An association between 2 species (“living
together”)
– Mutualism
– Parasitism
– Commensalism
Host-Microbe Relationships: Symbiosis
– Mutualism
• Both members benefit from relationship
• E. coli produce useful products (Vit K) in
our large intestine
E. Coli in Lg. intestines
– Parasitism
• One member benefits, one member is
harmed
Giardia in intestines
– Commensalism
• One member benefits, one member is not
benefited nor harmed
• Microbes on our skin utilize skin products
Demodex folliculorum in hair follicle
Resident Microflora
• Adult human body consists of:
– 10 trillion (10 13) eukaryotic cells-Human cells
– 100 trillion (10 14) prokaryotic cells-Bacteria cells
– We have 10 times as many prokaryotic cells vs. our
own cells!! How is this possible?
Resident Microflora
• Resident Microflora
• Microbes always present on or in the body
• Transient Microflora
• Microbes present for shorter periods of time (minutes to
months)
Resident Microflora
• Which areas harbor
microflora?
• What are some types of
normal microflora?
• Which body tissues,
organs and fluids are
usually microbe-free?
Types of microbes and the anatomic sites they occupy
The Absence of Resident Microflora can have Harmful
Effects
• Enlargement of
cecum
• Vitamin
deficiency
• Underdeveloped
immune system
Resident Microbial Antagonism
• normal biota are unlikely to be displaced by
incoming microbes
• limited number of attachment sites
• chemical or physiological environment created
by resident biota is hostile to other microbes
•Normal biota is beneficial, or at worst, commensal
to the host in good health with a functioning
immune system
First Acquiring Resident Microflora
•
•
•
•
•
•
Mother’s birth canal
Mother’s breast milk
Bottle-feeding
People
Air
Surfaces
• The only time that humans are sterile is when
they are in the womb (in utero)
Contamination, Infection and Disease
Contamination: Microbes are
present
Infection (Infestation-larger
parasites)
Multiplication of microbes (Microbes
penetrate host defenses, enter tissue
and MULTIPLY)
Disease
Disturbance in normal homeostasis
Invasion of normally sterile regions of the body can result in
infection and disease.
Factors that weaken host defenses and
increase susceptibility to infection
• old age and extreme youth (infancy, prematurity)
• genetic defects in immunity and acquired defects in
immunity (AIDS)
• surgery and organ transplants
• underlying disease: cancer, liver malfunction, diabetes
• chemotherapy/immunosuppressive drugs
• physical and mental stress
• pregnancy
• other infections
True vs. Opportunistic Pathogen
True pathogen
Vibrio cholerae
 Cause disease in healthy
individuals
 Associated with a specific and
recognizable disease
Staphylococcus aureus
Opportunistic pathogen
 Cause disease in immune
compromised host
 Gain access (injury) to sterile
regions
Opportunistic microbes
Opportunists usually do not cause
disease unless the “opportunity”
arises.
Conditions that opportunists can
flourish:
 Failure of the host’s normal defenses
 Immunocompromised populations
 Intro of the organism into unusual
body sites
 E. coli normal in gut but not urinary tract
 Disturbances in normal microflora
 Yeast infection after antibiotic use. Why?
Pathogens, Pathogenicity and Virulence
Pathogen
Disease causing agent
Pathogenicity
The ability to cause disease
Influenza
Virulence
The degree of pathogenicity
E. coli
The Progress of an Infection
Pathogen needs to become established by being
successful at the following:
1.
2.
3.
4.
5.
Portals of entry
Attachment
Surviving host defenses
Causing disease
Portals of exit
The Progress of an Infection
•Virulence of a microbe is determined by its ability to
- establish itself in a host
- cause damage
•Virulence factor: any characteristic or structure of the
microbe contributes to its ability to establish itself in the
host and cause damage
The Progress of an Infection:
1. Portal of Entry
•Portal of entry: the route that a microbe takes to enter
the tissues of the body to initiate an infection
•Exogenous: microbe originating from a source outside
the body from the environment or another person or
animal
•Endogenous: microbe already existing on or in the
body – normal biota or a previously silent infection
The Progress of an Infection:
1. Portals of Entry
• The majority of pathogens
have adapted to a specific
portal of entry
• if certain pathogens enter
the “wrong” portal, they
will not be infectious
• inoculation of the nasal
mucosa with the influenza
virus will result in infection,
but if the virus contacts the
skin, no infection occurs
The Progress of an Infection:
1. Portals of Entry
• Occasionally, an infectious
agent can enter by more
than one portal
• Mycobacterium tuberculosis
can enter through both the
respiratory and
gastrointestinal tracts
• Streptococcus and
Staphylococcus can enter
through the skin, urogenital
tract, and the respiratory
tract
The Progress of an Infection:
1. Portals of Entry
The Size of the Inoculum
•Infectious dose (ID)
- the minimum number of microbes necessary to cause an infection
to proceed
- microorganisms with smaller infectious doses have greater
virulence
-
ID for rickettsia is a single cell
ID for tuberculosis and beaver fever is about 10 cells
ID for gonorrhea is 1,000 cells
ID for typhoid fever is 10,000 cells
ID for cholera is 1,000,000,000 cells
The Progress of an Infection:
2. Attachment/Adhesion
-
-
-
gain a stable foothold on host
tissues
dependent on binding
between specific molecules
on both the host and pathogen
pathogen is limited to only
those cells (and organisms) to
which it can bind
firm attachment is almost
always a prerequisite for
causing disease since the
body has so many
mechanisms for flushing
microbes from tissues
The Progress of an Infection:
2. Attachment/Adhesion
Structures
– Capsules
– Pili or
fimbriae
– Hooks
The Progress of an Infection:
2. Attachment/Adhesion
Example of how fimbriae
and capsules are used to
adhere to the host cell.
The Progress of an Infection:
3. Surviving Host Defenses
•Microbes not established
as normal biota will likely
encounter the host
immune defenses when
first entering
•Phagocytes: cells that
engulf and destroy host
pathogens by means of
enzymes and
antimicrobial chemicals
WBC engulfing S. cerevisiae
The Progress of an Infection:
3. Surviving Host Defenses
•Antiphagocytic factors:
-
Virulence factors that help pathogens to avoid phagocytes
-
Leukocidins: kill phagocytes; Streptococcus and
Staphylococcus
-
Slime or capsule: makes it difficult for the phagocyte to
engulf the pathogen; Streptococcus
pneumoniae and
Salmonella typhi
-
Some bacteria survive inside the phagocyte; Legionella,
Mycobacterium
The Progress of an Infection:
3. Surviving Host Defenses
Humans have known for
centuries that copper is a
potent weapon against
infection. New research shows
that the bacteria that cause
serious urinary tract infections
steals copper from immune
cells to prevent the metal from
being used against them.
Nature Chemical Biology (July 8, 2012)
The Progress of an Infection:
4. Causing Disease
•Virulence factors are simply adaptations a microbe uses to
establish itself in a host
•Three ways that microorganisms cause damage to their host
A. directly through the action of enzymes
B. directly through the action of toxins (both endotoxins
and exotoxins)
C. indirectly by inducing the host’s defenses to respond
excessively or inappropriately
The Progress of an Infection:
4. Causing Disease-Enzymes
•Exoenzymes
- enzymes secreted by microbes that break down and inflict
damage on tissues
- dissolve the host’s defense barriers to promote the spread of
disease to other tissues
•Examples of exoenzymes
- hyaluronidase: digests the ground substance that
cements animal cells together
- coagulase: causes clotting of blood or plasma
The Progress of an Infection:
4. Causing Disease-Exoenzymes
The Progress of an Infection:
4. Causing Disease-Toxins
•Toxin: a specific chemical product of microbes, plants,
and some animals that causes cellular damage in other
organisms
•Toxins are named according to their target
- neurotoxins act on the nervous system
- enterotoxins act on the intestines
- hemotoxins lyse red blood cells
- nephrotoxins damage the kidneys
• Two types of toxins in pathogenic bacteria
• Exotoxin
• Endotoxin
The Progress of an Infection:
4. Causing Disease-Exotoxins
•Exotoxins
- proteins that targets a specific
cell type
-
affect cells by damaging the cell
membrane and initiating lysis
•Hemolysins
- disrupt the membrane of red
blood cells to release
hemoglobin
-
Ex. Streptococcus pyogenes and
Staphylococcus aureus
The Progress of an Infection:
4. Causing Disease-Endotoxins
• Endotoxin
- lipopolysaccharide (LPS), part of the outer membrane of
gram-negative cell walls
- Released when cells die
- has a variety of systemic effects on tissues and organs
- causes fever, inflammation, hemorrhage, and diarrhea
The Progress of an Infection:
4. Causing Disease-Endotoxins
Some endotoxins are pyrogenic
The Progress of an Infection:
5. Portal of Exit
• Enables pathogen to
spread to other hosts
– Respiratory
– Salivary
– Skin
– Fecal
– Urogenital
– Blood
The Progress of an Infection:
5. Portal of Exit
-
specific avenue by which pathogens exit
-
shed through secretion, excretion, discharge,
or sloughed tissue
-
high number of microbes in these materials
increases the likelihood that the pathogen will
reach other hosts
-
portal of exit is usually the same as the portal
of entry, but some pathogens use a different
route
The Progress of an Infection:
Establishment, Spread, and Pathologic Effects
•Microbes eventually settle in a particular target organ and cause
damage at the site
- host tissues are weakened as a result of the multiplication of the
pathogen
-
pathogens obstruct tubular structures such as blood vessels,
lymphatic channels, fallopian tubes, and bile ducts
-
necrosis: accumulated damage due to pathogens leading to cell
and tissue death
The Steps Involved When a Microbe Causes Disease
in a Host
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Finding a Portal
of Entry
Attaching Firmly
Surviving Host Defenses
Skin
GI tract
Respiratory tract
Urogenital tract
Endogenous biota
Fimbriae
Capsules
Surface proteins
Viral spikes
Avoiding phagocytosis
Avoiding death inside phagocyte
Absence of specific immunity
Causing Damage
(disease)
Direct damage
Toxins and/or
enzymes
Indirect damage
Inducing
inappropriate,
excessive host
response
Exiting Host
Portals of exit
Respiratory tract,
salivary glands
Skin cells
Fecal matter
Urogenital tract
Blood
Pathogenicity:
The ability to cause disease
Depends on a pathogen’s ability to:
1.
2.
3.
4.
5.
Enter
Attach
Survive host defenses
Cause disease
Exit
Look familiar?
Virulence: The degree of pathogenicity
• Intensity of disease produced
• Virulence can be decreased as a pathogen is subcultured time after time
• Many virulence factors (weapons) exist to
increase a pathogen’s ability to:
1.
2.
3.
4.
5.
Enter
Attach
Survive host defenses
Cause disease
Exit
Establishment of Infections
• Localized infection: An
infection that is limited to a
specific part of the body and
has local symptoms
• Systemic infection: pathogen
is distributed throughout the
body
Establishment of Infections
• Focal infection: A
bacterial infection
localized in a specific part
of the body, that spreads
to other parts of the
body
• Mixed infection: Bacterial
infection composed of
different species of
bacteria
Establishment of Infections
• Primary and secondary
infections: Illness caused by
new microbe becoming
established in the wake of an
initial (primary) infection
• Acute: rapid onset of infection,
short course of infection
• Chronic: Long duration of
infection
Infections That Go Unnoticed
•No noticeable symptoms are produced
•Microbe is present in host tissues
•Host does not seek medical attention
•These infections are known as
asymptomatic or subclinical
Signs, Symptoms and Syndromes
• Signs
• Objective/measurable (I.e., fever, inflammation)
• Symptoms
• Subjective (pain, tummy ache)
• Syndromes
• Combo of signs and symptoms that occur together
• How would you classify a sore throat? A red throat? A
fever?
Some commons signs and symptoms associated with infectious diseases
Stages of an Infectious Disease
Incubation periods vary
The Persistence of Microbes and
Pathologic Conditions
•Recovery of the host does not always mean the microbe
has been removed or destroyed by host defenses
•Latency: a dormant state of microbes in certain chronic
infectious diseases
-
viral latency: herpes simplex, herpes zoster,
hepatitis B, AIDS, Epstein-Barr
-
bacterial/protozoan latency: syphilis, typhoid
fever, tuberculosis, malaria
The Persistence of Microbes and
Pathologic Conditions
•Sequelae: long-term or permanent damage to tissues
or organs caused by infectious disease
-
meningitis: deafness
-
strep throat: rheumatic heart disease
-
Lyme disease: arthritis
-
polio: paralysis
Epidemiology
Epidemiology
• What is it?
– The study of disease within populations (human,
plant, etc.)
• Why do we care?
– Helps us investigate the factors regarding a specific
disease.
•
•
•
•
what causes a disease
how is it transmitted
how do we prevent and treat it
how many people are afflicted.
Epidemiology
• Epidemiology allows us to take all we have
learned about microbes and the diseases
they cause and apply that knowledge to new
situations.
• Involves many disciplines: microbiology,
anatomy, physiology, immunology, medicine,
psychology, sociology, ecology, and statistics
Epidemiology Terminology
• Epidemiologists
• “disease detectives”, scientists who study epidemiology
• Etiologic agent
• The cause of a disease
• Morbidity
• Illness
• Mortality
• Death
Epidemiology Terminology
• Incidence
• Number of NEW cases
within a period of time
• Prevalence
• TOTAL number of cases
within a period of time
• Which one informs us if
we have taken proper
measures to halt disease
transmission?
Epidemiology Terminology
Tracking Disease in the Population
•Reportable or notifiable diseases
- certain diseases must be reported to authorities
-
other diseases are reported on a voluntary
basis
•A network of agencies at the local, district, state,
national, and international levels keeps track of
infectious diseases
Epidemiology Terminology
– Endemic
– Pathogen is continually present in population
– Sporadic
– occasional cases are reported at irregular intervals at random
locales
– Epidemic
– An “outbreak” or higher than normal number of cases. Ie.
prevalence of an endemic or sporadic disease is increasing
beyond what is expected for a population
– Pandemic
– Spread of an epidemic across continents
Epidemiology Terminology
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Endemic Occurrence
Epidemic Occurrence
Cases
(a)
(c)
Sporadic Occurrence
Pandemic Occurrence
The incidence rate of chicken pox in
the U.S.
Is this disease endemic, epidemic, pandemic or sporadic?
Diphtheria cases after the break up
of the former Soviet Union.
Is this disease endemic, epidemic, pandemic or sporadic?
Epidemiology Terminology
•Point-source epidemic: infectious agent came from a single
source, and all of its “victims” were exposed to it from that
source
•Common-source epidemic: result from common exposure
to a single source of infection over a period of time
•Propagated epidemic: results from an infectious agent that
is communicable from person to person and is sustained
over time in a population
Statistical data can be represented graphically, and
can be used to predict trends
We can analyze the data according to
year, ages affected, and geographic
location to help us predict what
diseases we need to watch out for
and identify precautions to prevent
them. (similar to Influenza H5N1)
Commonly reported diseases that are tracked in
the United States
Epidemiologic Studies
• Epidemiologists collect data on diseases to
help prevent outbreaks in the future.
• Three Types of Epidemiologic Studies:
– Descriptive
– Analytical
– Experimental
First formal epidemiologic study performed by John Snow in 1854. He
traced the source of a cholera epidemic to a certain water pump and
proved that people became infected by fecally contaminated drinking
water.
Descriptive Studies
• Concerned with the physical
aspects of an existing
disease and disease spread.
• Provides the what, who,
when and where
• Records as many details as
possible:
–
–
–
–
Number of cases
Populations affected
Locations and time
Age, gender, race,
socioeconomic status, etc.
Examples of Data from
Descriptive Studies
Analytical Studies
• Provides the why and how
• Studies determine causes and
factors that influence the rate of
disease. These factors include
demographic, biological, behavioral,
and environmental influences.
• Disease groups are compared to
control groups and data is analyzed
for similarities and differences.
Example analytical question: in the
hanta virus epidemic, did people get
sick if they had been outside near mice
habitats or if they had been cooped up
in office buildings?
Example of Data from
Analytical Studies
(red -> higher risk)
Bovine brucellosis cumulative incidence, 1995-99
(red -> higher risk)
Bovine tuberculosis cumulative incidence, 1995-99
Notice the similarity in the distribution of
the high risk areas, suggesting that the
two diseases are associated
Experimental Studies
• Designs experiments to test a hypothesis.
• These are the “cleanest” types of studies and
often considered the gold-standard.
• Many experimental studies are performed for
pharmaceutical (“clinical trials”) or other
treatments.
Example of Data from Experimental Studies
Non-infected mice
Mucus cells 10-3/µm2
• Mice were infected for
24 hours with wild type
P. aeruginosa strain or
a P. aeruginosa
flagellin-deficient
mutant
• Lung histology analysis
of non-infected, WT
infected, and flagellindeficient mutant
infected mice. Blue
cells are mucus
producing cells
induced by P.
aeruginosa.
Infected with +flagella P. aeruginosa
Infected with -flagella P. aeruginosa
Conclusion: flagella
are needed for P.
aeruginosa to induce
mucus producing cells
Disease Transmission
• Disease transmission is affected by:
– Reservoirs of infection
– Portals of Entry and Exit
– Mechanisms of Transmission
– We will investigate all three in order to understand
how to break the chain of disease transmission.
You can break it at just one site to stop
transmission.
Disease Transmission:
Source of Infection
• Reservoir
• The natural host or habitat (living or nonliving) of a
pathogen
• Source
• The person or item from which an infection is DIRECTLY
acquired
• Carrier vs. Asymptomatic Carrier
• An organism that harbors infections and can spread them to
others. They may show symptoms or not.
Disease Transmission:
Source of Infection
• Biological vector
• An organism which not only TRANSPORTS a pathogen but
ALSO plays a role in the LIFE CYCLE of the pathogen (virus
inside of mosquito, bacteria inside of tick)
• Mechanical vector
• An organism which ONLY TRANSPORTS a pathogen (fly)
Disease Transmission:
Source of Infection
• Zoonosis
• An infectious disease indigenous to ANIMALS that
humans CAN acquire through direct or indirect contact.
(rabies)
• make up a full 70% of all new emerging diseases
worldwide
• impossible to eradicate without also eradicating the
animal reservoir
• attempts have been made to eradicate mosquitoes and
certain rodents
Zoonotic
infections are
caused by
vectors and
animal
reservoirs
spreading their
own infections
to humans
Disease Transmission:
Source of Infection
• Human Reservoirs
• Asymptomatic Carrier
• Symptomatic Carriers
• Animal Reservoirs
• Wild animals (Rabies)
• Deer mice (hanta virus)
• Nonliving Reservoirs
• Soil (Clostridium tetani, Bacillus anthracis)
• Water (Cholera, Giardia)
• Food (E. coli, Salmonella, Listeria)
Disease Transmission:
Source of Infection
• Some diseases are communicable but others are
not
• Communicable
• Infected host transmits an infectious agent to another host
• Receiving host must become infected
• Non-communicable
• Host acquires infectious agent but can’t transmit it to another
– From self (compromised individual)- microflora
– Nonliving reservoir – soil-(tetanus)
Disease Transmission:
Source of Infection
• Communicable
– Disease spread from one host to another
• I.e., cold, meningitis
• Contagious
– EASILY communicable
• I.e. measles, influenza
– Are all communicable diseases contagious?
– Are all contagious disease communicable?
Disease Transmission:
Portal of Exit and
Entrance
•
Respiratory pathogens are
usually inhaled or enter
via the eye.
•
Digestive pathogens are
usually ingested.
– (Can you get an E. coli
infection by inhaling
cow poop?)
•
Intact skin prevents many
microbial invasions.
Watch out for those paper
cuts!
Disease Transmission:
Patterns of Transmission
• Horizontal transmission
• Disease is spread through a population from one
infected person to another
– Kissing, sneezing
• Vertical transmission
• The disease is transmitted from parent to offspring
– Ovum, sperm, placenta, milk
Disease Transmission:
Patterns of Transmission
• Direct (contact)
• Kissing, sex
• Droplets (sneezing,
coughing directly upon a
person within 3 feet)
• Vertical
• Vector
• Indirect
– Contaminated materials
• Vehicles=Food, water,
biological products (blood,
serum, tissue), FOMITE
(door knobs, toilet seats,
etc.)
• Fecal-oral (aka oral-fecal)
– Air (greater than 3 feet
away)
• Droplet nuclei (dried
microscopic residue)
• Aerosols (dust or moisture
particles)
A sneeze can release enormous amounts of moist droplets,
and the dry droplets form droplet nuclei. (SO COVER YOUR
MOUTH WITH YOUR ELBOW )
Disease Transmission: REVIEW
• Disease transmission is affected by:
– Reservoirs of infection
– Portals of Entry and Exit
– Mechanisms of Transmission
– You can break the transmission of disease at each
of the above levels!!
Disease Transmission: Prevention
• Sanitation
– What is the #1 way to stop disease?
•
•
•
•
•
Immunization
Isolation
Quarantine
Control vectors
Education about prevention and treatment
Disease Transmission: Prevention
• Herd immunity is the
proportion of people
immune to a certain
disease. Is it easier or
more difficult to
transmit disease when
herd immunity is low?
How do we acquire herd
immunity?
Disease Transmission: Prevention
and Public Health Organizations
• Created to control disease
• They monitor NOTIFIABLE (reportable) DISEASES
• A list of notifiable diseases promotes cooperation between
the different health agencies. These are diseases that are
particularly harmful to humans and infectious and must be
monitored to protect the population.
• Many levels:
• County Health Department
• State Health Department
• Centers for Disease Control and Prevention (CDC-a federal
health department)
• World Health Organization (WHO)
Nosocomial Infections
Nosocomial Infections:
The Hospital as Source of Disease
• An infection acquired in a hospital
• Patient enters the hospital with tuberculosis. Is
this a nosocomial infection?
• Patient enters hospital with a broken hip. After
surgery and during recuperation, she acquires
an urinary tract infection (UTI). Is this a
nosocomial infection?
Nosocomial Infections:
The Hospital as Source of Disease
• About 2-4 million (5-20 percent) of
admitted patients acquire a nosocomial
infection
• 90, 000 die of nosocomial infections
• $5-10 billion per year to treat nosocomial
infections
Nosocomial Infections:
Contributing Factors
-
compromised patients
-
collection point for pathogens
-
lowered defenses permit normal biota to enter the body
-
infections acquired directly or indirectly from fomites,
medical equipment, other patients, medical personnel,
visitors, air, and water
Epidemiology of Nosocomial Infections
Epidemiology investigates:
• Sources of Infection
• Modes of Transmission
• Susceptibility to Infection
• Prevention
• Control
• Risk Factors
• Sites of Infection
Nosocomial Infections: Source
Exogenous
○ Other patients
○ Staff
○ Visitors
○ Insects (ants, roaches, flies)
○ Fomites (floor, trash can, counters, catheters, bathroom
fixtures, medical equipment like nebulizers and dialysis
machines, tubing, syringes, needles)
Endogenous
○ Opportunists among patient’s own normal microflora
Nosocomial Infections: Source
There are many possible sites of contamination that can
lead to infection.
Nosocomial Infections: Source
Some common modes of transmission of nosocomial
infections
The
most common
nosocomial
infections
Common nosocomial pathogens
Nosocomial Infections:
Prevention and Control
•Healthcare processes that lead to nosocomial
infections:
-
treatments using reusable instruments such
as respirators and thermometers
-
indwelling devices such as catheters, prosthetic
heart valves, grafts, drainage tubes, and
tracheostomy tubes form ready portals of entry
-
high proportion of the hospital population
receives antimicrobial therapy, drug-resistant
microbes are selected for at a much higher rate
Nosocomial Infections:
Prevention and Control
• Recent evidence suggests that more than 1/3 of
nosocomial infections could be avoided by
consistent and rigorous infection control methods
• Use Universal Precautions (aka Standard
Precautions)
• Assume all patients and fomites may harbor
pathogens
• Use caution and compassion
Nosocomial Infections:
Prevention and Control
• To maintain accreditation by the American Hospital
Association, all hospitals must have:
–
–
–
–
–
–
–
Surveillance methods and data
Microbiology laboratory
Isolation procedures
Standard operating procedures (SOPs) for equipment
General sanitation procedures
Disease education programs
What is the single most important technique to prevent
nosocomial infections?