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Transcript
Microbe-Human Interactions:
Infection and Disease
Chapter 13
Adapted from McGraw Hill
by Dr. G Cornwall
13.1 The Human Host
• Contact, Infection, Disease- A Continuum
• Body surfaces are constantly exposed to microbes
• Inevitably leads to infection: pathogenic microorganisms
penetrate the host defenses, enter the tissues, and multiply
• Pathologic state that results when the infection damages or
disrupts tissues and organs = disease
• Infectious disease: the disruption of a tissue or organ
caused by microbes or their products
• Host-Parasite relationship
• contact - not all contacts lead to colonization
• progress to infection
• disease
Resident Biota
• Resident Biota: The Human as a Habitat
• Cell for cell, microbes on the human body outnumber human
cells at least ten to one
• Human cells in an adult is about 10 trillion
• Bacteria in and on an adult is about 100 trillion
• Normal (resident) biota - adapted to live here on us
• Metagenomics being used to identify the microbial profile inside
and on humans
• Human Microbiome Project
• Acquiring Resident Biota
• The body provides a wide range of habitats and supports a wide
range of microbes
Normal Microbiota
• Resident Microbes
• each site has particular populations
• changes over time
• Transient Microbes
• do not normally reside, just passing through
• most are harmless, some pathogens
• Opportunists
• cause disease when given opportunity
• breakdown in immunity
• certain medical treatments
• implantation of devices
Sites Thought to be Sterile
Impact of the Normal Flora
• Organ Development is influenced by presence of resident biota
• Prevent overgrowth of harmful microbes (e.g lactobacilli & yeasts
in vagina)
• Microbial antagonism: antagonism of “good” microbes against
intruders
• residents are unlikely to be displaced by intruders
• production of a chemical or physiological environment that in
unfavorable to intruders
• Composition of intestinal biota may influence your tendency to be
overweight
• obese humans have more firmicutes, and less bacteroidetes
• firmicutes may draw more calories out of food
• Whether we can call a microbe beneficial depends on an individuals good
health and fully functional immune system
• disease could easily be caused by previously normal biota
• Endogenous Infections - caused by endogenous biota (AIDS, or
introduction in to sterile organ - Bladder infection)
• What about Viruses as normal Biota?
• now finding that some may have coevolved with us to be beneficial
• ERV’s are vital to healthy placental development in sheep
• T-lymphotrophic virus = lower incidence of stomach cancer
(mutualistic and protective role)
Initial Colonization of a Newborn
• Birth canal - vaginal biota are
the first to colonize when
membranes break
• C-section means skin biota
are first
• either way mostly from
mother
• Food - breast or Bottle
(formula) makes a HUGE
difference
• Breathing
• Healthcare professionals
Concept Check
Which of the following do not normally contain
microbiota?
A. Skin
B. Liver and kidneys
C. Vagina
D. Upper respiratory system
13.2 The Progress of an Infection
• Pathogen: a microbe
whose relationship with its
host is parasitic and results
in infection and disease
• True vs Opportunistic
• Type and severity of
infection depend on
pathogenicity of the
organism and the condition
of its host
• Opportunistic Pathogens
cause disease when hosts
defenses are compromised
Virulence
• The degree of pathogenicity
• Determined by its ability to
• Establish itself in the host
• Cause damage
• Virulence factor: any characteristic or structure of
the microbe that contributes to its virulence
• Different healthy individuals have widely varying
responses to the same microorganism: hosts evolve
Becoming Established: Step OnePortals of Entry
• Microbe enters the tissues of the body by a portal
of entry
• Usually a cutaneous or membranous boundary
• Exogenous or Endogenous Sources
• Normally the same anatomical regions that
support normal biota: Skin, GI tract, Respiratory
tract, and urogenital tract
• the majority of pathogens have adapted to a
specific portal of entry, although some are
adapted to several
Infectious Agents that Enter the Skin
• Nicks, abrasions, and punctures
• Intact skin is very tough- few microbes can penetrate
• Some create their own passageways using digestive
enzymes or bites
• certain helminth worms
• bites from insects or other animals carrying microbes
• contaminated needles - HIV, hepatitis, tetanus
• Examples
• Staphylococcus aureus (boils)
• Streptococcus pyogenes (impetigo)
• Haemophilus aegyptius (pink eye)
• Chalmydia trachomatis (trachoma - granular conjunctivitis)
• Neisseria gonorrhoeae
The Gastrointestinal Tract as Portal
• Pathogens contained in food, drink, and other
ingested substances
• Adapted to survive digestive enzymes and pH
changes
• Examples
• Salmonella, Shigella, Vibrio, Certain strains of
Escherichia coli, Poliovirus, Hepatitis A virus,
Echovirus, Rotavirus, Entamoeba histolytica,
Giardia lamblia
The Respiratory Portal of Entry
• The portal of entry for the greatest number of pathogens
• continuous membrane surface covering the upper
respiratory tract, sinuses, and auditory tubes allows
microbes to be transferred from one site to another
• Examples
• Streptococcal sore throat, Meningitis, Diphtheria,
Whooping cough, Influenza, Measles, Mumps,
Rubella, Chickenpox, Common cold
• Bacteria and fungi can cause pneumonias when
smaller pathogens that are inhaled into lower
regions of respiratory tract
Urogenital Portals of Entry
• Sexually transmitted diseases (STDs) - 4% of infections
worldwide - approximately 13 million new cases in the US
each year
• Enter skin or mucosa of penis, external genitalia, vagina,
cervix, and urethra
• Some can penetrate an unbroken surface
• Examples
• Syphilis
• Genital warts
• Chlamydia
• Herpes
• Trichomonas (a protozoan)
• HIV, Hepatitis B
• Not all urogenital infections are STD’s
Pathogens that Infect During Pregnancy and
Birth
• Some microbes can cross the placenta (ex. the syphilis
spirochete)
• Other infections occur perinatally when the child is
contaminated by the birth canal
• TORCH (toxoplasmosis, other diseases, rubella,
cytomegalovirus, and herpes simplex)
The Size of the Inoculum:
• The quantity of microbes in the inoculating dose
• For most agents, infection only proceeds if the infectious dose
(ID) is present
• in general, microorganisms with smaller IDs have greater
virulence
• ID for causative agent of Q fever is 1 infectious cell
• Only 10 infectious cells for tuberculosis
• Gonorrhea ID = 1,000
• Cholera ID = 1,000,000,000
• Numbers below the ID will generally not cause infection,
however if there is a much higher quantity then onset can be
extremely rapid
Becoming Established: Step TwoAttaching to the Host (Adhesion)
Adhesion is a process by which
microbes gain a more stable
foothold
• Bind with
• Fimbriae (pili)
• surface proteins, and
adhesive slimes or
capsules
• viral envelope spikes
• suckers, hooks, or barbs
• pathogens are limited to only
those cells to which it can bind
Becoming Established: Step ThreeSurviving Host Defenses
• Phagocytes -White blood cells that engulf and destroy
pathogens
• Antiphagocytic factors: used by some pathogens to
avoid phagocytes
• Leukocidins: toxic to white blood cells, produced by
Streptococcus and Staphylococcus
• Extracellular surface layer: makes it difficult for the phagocyte to
engulf them, for example- Streptococcus pneumonia, Salmonella
typhi, Neisseria meningitides, and Cryptococcus neoformans
• Some can survive inside phagocytes after ingestion: Legionella,
Mycobacterium, and many rickettsias
Causing Disease: How Virulence Factors
Contribute to Tissue Damage
• virulence factors are adaptations
used by microbes to invade and
establish itself in the host
• determine the degree of tissue
damage
• effect varies greatly
• Microorganisms inflict damage by:
• use of exoenzymes and toxins
• cause damage indirectly - their
presence causes an excessive
or inappropriate response
(most cases)
Extracellular Enzymes
• Break down and inflict damage on tissues or dissolve
the host’s defense barriers
• Examples
• Mucinase
• Keratinase
• Collagenase
• Hyaluronidase
• Some react with components of the blood
• Coagulase causes clotting of blood or plasma
(staphylococci)
• Kinases (streptokinase, and staphylokinase) do the
opposite (dissolve fibrin clots to expedite invasion)
Bacterial Toxins
• Toxins are specific chemical
products that are poisonous to other
organisms
• Toxigenicity: the power to produce
toxins
• Toxinoses: a variety of diseases
caused by toxigenicity
• Toxemias: the toxin is spread by
the blood from the site of
infection (tetanus and diphtheria)
• Intoxications: ingestion of
toxins (botulism)
• Toxins are named according to the
specific target of action (neurotoxin,
enterotoxins, hemotoxins,
nephrotoxins)
Endotoxins and Exotoxins
Toxins can also be classified according to
their origins
• Exotoxins are secreted by a living
bacterial cell into the infected tissue
• have highly specific targets, and
physiological effects (many varieties)
• Endotoxins are not actively secretes, but
are shed from the outer membrane
• given off when cell wall of gramnegative bacteria disintegrates (lipopolysaccharide / LPS)
• has more generalized physiological
effects
Concept Check
Which of the following is not an exoenzyme?
A. Botulism toxin
B. Keratinase
C. Mucinase
D. Collagenase
The Process of Infection and Disease
• Establishment, Spread, and Pathologic Effects
• Microbes eventually settle in a particular target organ and
continue to cause damage at the site
• In addition to the effects of enzymes and toxins, multiplication
of the pathogen frequently weakens host tissues
• Pathogens can obstruct tubular structures (blood vessels,
lymphatic vessels, and fallopian tubes, bile ducts)
• Necrosis: accumulated damage leads to cell and tissue
death
• Viruses do not produce toxins or exoenzymes
• multiply and lyse cells
• many cytopathic effects from impaired metabolism and
death of cells
Progression of Infection
• Incubation period
• Prodromal
• Invasion
• Convalescence
Patterns of Infection
• Localized: pathogen is restricted to a specific site
• Systemic: pathogen spreads through circulation to many sites
• Focal Infection: initially a local infection, but circumstances cause the
pathogen to be carried to many other sites
• Mixed Infection: same site infected with multiple microbes
• Primary- Secondary: initial infection is complicated by a second one in same
or different location
• Acute vs Chronic
Stages in Infections
Signs and Symptoms: Warning Signals
of Disease
• Sign: any objective
evidence of disease as
noted by an observer
• Symptom: the
subjective evidence of
disease as sensed by
the patient
• Syndrome: when a
disease can be
identified or defined by
a certain complex of
signs and symptoms
Signs and Symptoms of
Inflammation
• Fever, pain, soreness, swelling
• Edema
• Granulomas and abscesses
• Lymphadenitis
• Lesion: the site of infection or disease including rashes or other skin eruptions
Signs of Infection in the Blood
• Changes in the number of circulating white blood cells are
considered to be signs of possible infection
• Leukocytosis = increase in level of WBC’s
• Leukopenia = a decrease in WBC’s
• Other signs of infection include presence of a microbe, or its
products in the blood
• Septicemia: general state in which microorganisms are
multiplying in the blood and are present in large numbers
• Bacteremia or viremia: microbes are present in the blood
but are not necessarily multiplying
• Immune response (antibodies in serum)
• basis of several serological tests
• Asymptomatic or Subclinical = unnoticed infections
Exit Portals
In most cases the pathogen is
released from the body through
secretions, excretion, discharge
or sloughed tissue
• Respiratory and Salivary Portals
• Coughing and sneezing
• Talking and laughing
• Skin Scales
• Fecal Exit
• Urogenital Tract
• Removal of Blood or Bleeding
The Persistence of Microbes and
Pathologic Conditions
• Latency: a dormant state
• The microbe can periodically become active and
produce a recurrent disease
• microbe may or may not be shed during latency
• Examples of persistent infectious agents
• Herpes simplex, Herpes Zoster
• Hepatitis B
• AIDS
• Epstein-Barr
• Sequelae: long-term or permanent damage to tissues
or organs
Reservoirs: Where Pathogens Persist
• Reservoir: the primary habitat in the natural world from
which a pathogen originates
• Source: the individual or object from which an infection
is actually acquired
• Living Reservoirs
• Carrier: an individual who inconspicuously shelters a
pathogen and spreads it to others without any notice
• Asymptomatic carriers
• Incubation carriers
• Convalescent carriers
• Chronic carrier
• Passive carrier
Animals as Reservoirs and Sources
• Vector: a live animal that transmits an infectious agent from one
host to another
• Majority are arthropods
• Larger animals can also be vectors
• Biological vector: actively participates in a pathogen’s life cycle
• Mechanical vectors: transport the infectious agent without
being infected
• Zoonosis: an infection indigenous
to animals but naturally
transmissible to humans
• People in animal oriented
outdoor professions are at the
greatest risk
• At least 150 worldwide
• make up 70% or emerging
diseases worldwide
• mostly due to environmental
destruction (deforestation,
urban sprawl) - animals
have to find new habitat
Nonliving Reservoirs
• Microorganisms have adapted to nearly every
habitat in the biosphere
• they thrive in soil and water
• most are saprobic, and of benefit to us
• Human hosts in regular contact with
environmental sources
Concept Check
Which of the following is a symptom?
A. Elevated white blood cell count
B.Fever
C. Nausea
D. Swollen lymph nodes
Acquisition and Transmission of
Infectious Agents
• Communicable disease: when an infected host can
transmit the infectious agent to another host and establish
infection in that host
• Transmission can be direct or indirect
• If the agent is highly communicable, it s considered
Contagious
• Noncommunicable disease: does not arise through
transmission of the infectious agent from host to host
• Acquired through some other, special circumstance
• Compromised person invaded by his or her own
microbiota
• Individual has accidental contact with a microbe in a
nonliving reservoir (tetanus)
Transmission
Direct (Contact) transmission
• Touching
• Kissing
• Sexual Intercourse
• Bites by biological vectors
• Vertical transmission
• prenatal -- across placenta
• perinatal -- during or shortly after birth
• Droplet contact - spray from sneezing or coughing
Indirect transmission
• Vehicle: any inanimate material commonly used by humans that
can transmit infectious agents (food, water, biological products,
fomites)
• Fomites: Contaminated objects (doorknobs, telephones, remote
controls, faucets etc.)
• Food poisoning (soil, handler, mechanical vector)
• Oral-fecal route (contaminated toys, handler with inadequate
personal hygiene)
• Air as a vehicle
• Indoor air
• Droplet nuclei
• Aerosols
Nosocomial Infections: The Hospital as a
Source of Disease
• Nosocomial infections: infectious
diseases that are acquired or
develop during a hospital stay
• 2-4 million cases a year, resulting
in nearly 90,000 deaths
• Most common = urinary tract,
respiratory tract and surgical site
infections
• The importance of medical
asepsis
Universal Blood and Body Fluid
Precautions
• Universal precautions (UPs): guidelines from
the Centers for Disease Control and Prevention
• Assume that all patient specimens could
harbor infectious agents
• Include body substance isolation
(BSI)techniques to be used in known cases of
infection
• precautions designed to protect ALL
individuals in clinical settings (patients,
workers, and public)
Which Agent is the Cause? Using Koch’s
Postulates to Determine Etiology
• Etiologic agent: the causative agent
• Robert Koch: developed a standard for
determining causation that would stand the
test of scientific scrutiny
• Koch’s Postulates
• Find evidence of a particular microbe in
every case of a disease
• Isolate that microbe from an infected
subject and cultivate it in pure culture in
the laboratory
• Inoculate a susceptible healthy subject
with the laboratory isolate and observe
the same resultant disease
• Re-isolate the agent from this subject
13.3 Epidemiology: The Study of
Disease in Populations
• Epidemiology: the study of the frequency
and distribution of disease and other
health-related factors in defined human
populations
• Involves not only microbiology but also
anatomy, physiology, immunology,
medicine, psychology, sociology, ecology,
and statistics
Who, When, and Where? Tracking
Disease in the Population
• Epidemiologists concerned with virulence, portals of entry
and exit, and the course of the disease
• Also interested in surveillance - collection and analysis of
data on rates of occurrence, mortality, morbidity, and
transmission
• Reportable diseases: by law, must be reported to
authorities (specified diseases)
• Centers for Disease Control and Prevention (CDC) in
Atlanta, Georgia
• Weekly notice: the Morbidity and Mortality Report
• Shares statistics with the World Health Organization
(WHO)
Epidemiological Statistics
• Prevalence rate: total number of existing
cases with respect to the entire
population
• Incidence rate: the number of new cases
over a certain period of time (case or
morbidity rate)
• of particular interest are statistics on sex,
race, or geographic region
• Mortality rate: total number of deaths in
a population due to certain disease
Examination of epidemic curve
(incidence rate over time) can
determine if infection is:
• point-source - all victims exposed
from a single source (contaminated
food item at potluck)
• common-source - common
exposure to a single source over
time (contaminated water source)
• propagated epidemic communicable infectious agent
(influenza)
• Index case - the first patient found
in epidemiological investigation
Epidemiology is the Study of occurrence of disease
• When, where, and how is it transmitted?
• Endemic
• Chronic occurrence in a geographical region
• Sporadic
• Random small outbreaks
• Epidemic
• Sudden acute disease outbreak affecting many people
• Pandemic
• A worldwide epidemic (across geopolitical boundaries)
Concept Check
What term refers to the rapid increase in the
incidence of a disease in a localized
geographical region?
A.Endemic
B.Pandemic
C.Sporadic
D.Epidemic