chapter 13 microbe-human interactions
TRANSCRIPT
Chapter 13
Microbe-Human Interactions
Infection, Disease, and Epidemiology
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
2
13.1 We Are Not Alone
• The human body exists in a state of dynamic
equilibrium
• Many interactions between human body and
microorganisms involve the development of
biofilms
• Colonization of the body involves a constant
“give and take”
3
Contact, Colonization, Infection, Disease
• Microbes that engage in mutual or commensal associations – normal (resident) flora, indigenous flora, microbiota
• Infection – a condition in which pathogenic microbes penetrate host defenses, enter tissues, and multiply
• Pathogen – infectious agent
• Infectious disease – an infection that causes damage or disruption to tissues and organs
4
Contact, Colonization, Infection, Disease
Microbes adhere to
exposed body surfaces
INVASION
Microbes cross lines of
defense and enter
sterile tissues
INFECTION
Pathogenic microbes
multiply in the tissues
Colonization with
microbiota
Defenses hold
pathogen in check
Effects of microbes
result in injury or
disruption to
tissues
Morbidity/mortality
occur
Action of
microbes
Beneficial
effects
Adverse
effects
*** Some pathogens may remain hidden in the body
Immunity/repair of
damage
Carrier state develops
Microbes are established
in tissues but disease is
not apparent
**
***
1
2
3
4
* Not all contacts lead to colonization or infection.
** Microbiota may invade, especially if defenses are compromised.
CONTACT*
Meninges
(of brain)
Middle ear
Pharynx
Bronchus
Alveolus
Palate
Sinus
Nasal mucosa
Bronchiole
Trachea 1
2
3
4 4
4
Figure 13.1 Associations
between microbes and humans
5
Resident Microbiota: The Human as a Habitat
• Most areas of the body in contact with the outside environment harbor resident microbes
• Internal organs, tissues, and fluids are microbe-free
• Transients – microbes that occupy the body for only short periods
• Residents – microbes that become established
6
The Human as a Habitat
• Bacterial flora benefit host by preventing overgrowth of harmful microbes – microbial antagonism
• Endogenous infections – occur when normal flora is introduced to a site that was previously sterile
7
Initial Colonization of the Newborn
• Uterus and contents are
normally sterile and
remain so until just
before birth
• Breaking of fetal
membrane exposes the
infant; all subsequent
handling and feeding
continue to introduce
what will be normal flora
Figure 13.2 The origins of microbiota in
newborns
8
Colonizers of the Human Skin
• Skin is the largest and most accessible organ
• Two cutaneous populations – Transients:
influenced by hygiene
– Residents: stable, predictable, less influenced by hygiene
Duct of
sudoriferous
(sweat) gland
Subcutaneous
tissue
(a)
Hair root
Hair follicle
Sebaceous
(oil) gland
Sweat pores
Hair shaft
Dermis
Epidermis
(b)
Janice Carr/CDC
Figure 13.3 The landscape of the skin –
a. location of microbes, colored areas
b. magnified view showing bacteria
9
Microbial Residents of the Gastrointestinal Tract
• GI tract is a long hollow tube, bounded by mucous membranes
– Tube is exposed to the environment
• Variations in flora distribution due to shifting conditions (pH, oxygen tension, anatomy)
• Oral cavity, large intestine, and rectum harbor appreciable flora
Pharynx
Esophagus
Duodenum
Large
intestine
Small
intestine
Rectum
Anal canal
Stomach
Oral cavity
Figure 13.4 Distribution of microbes,
colored areas
10
Flora of the Mouth
• Most diverse and unique flora of the body
• Numerous adaptive niches
• Bacterial count of saliva (5 x 109 cells per
milliliter)
• Most common are: Streptococcus species
11
Flora of the Large Intestine
• Has complex and profound interactions with
host
• 108-1011 microbes per gram of feces
• Intestinal environment favors anaerobic
bacteria
• Intestinal bacteria contribute to intestinal
odor, called skatole, or when it escapes it is
called flatulence
12
Inhabitants of the Respiratory Tract
• Oral streptococci, first organisms to colonize
• Nasal entrance, nasal vestibule, anterior nasopharynx – S. aureus
• Mucous membranes of nasopharynx – Neisseria
• Tonsils and lower pharynx – Haemophilus
Nasal
vestibule
Nasal
entrance
Nasal cavity
Larynx
Bronchus
Bronchiol e
Internal naris
Soft palate
Nasopharynx
Epiglottis
Trachea
Right lung Left lung
Sinuses
Figure 13.5 Colonized regions of the
respiratory tract, colored areas
13
Microbiota of the Genitourinary Tract
• Sites that harbor microflora
– Females: Vagina and
outer opening of urethra
– Males: Anterior urethra
• Changes in physiology
influence the composition
of the normal flora
– Vagina (estrogen,
glycogen, pH)
Anus
Uterine tube
Ovary
Urinary
bladder
Urethra
External
reproductive
organs
Urinary
bladder
Penis
Urethra
Testis
Rectum
Vagina
Anus
Rectum
Uterus
Figure 13.6 Microbiota of the
reproductive tract, in colored
areas
14
Maintenance of the Normal Microbiota
• Normal flora is essential to the health of
humans
• Flora create an environment that may prevent
infections and can enhance host defenses
• Antibiotics, dietary changes, and disease may
alter flora
• Probiotics – introducing known microbes
back into the body, they are beneficial and
nonpathogenic
15
13.2 Major Factors in the Development of an Infection
Microbes
evade barriers
Portal
of entry Adhesion
Microbes attach
to host cells
Invasion
Microbes make
pathway into cells
Multiplication
Microbes grow
and spread
Infection of target
Microbes attack
specific tissues
Microbes
damage tissues
Microbes
leave host
Disease Portal
of exit
Figure 13.7 Flow diagram that reflects the events in entry, establishment,
and exit of infectious agents
16
Major Factors in the Development of an Infection
• True pathogens – capable of causing disease in healthy persons with normal immune defenses
– Influenza virus, plague bacillus, malarial protozoan
• Opportunistic pathogens – cause disease when the host’s defenses are compromised or when they grow in part of the body that is not natural to them
– Pseudomonas sp & Candida albicans
• Severity of the disease depends on the virulence of the pathogen; characteristic or structure that contributes to the ability of a microbe to cause disease is a virulence factor.
Biosafety Levels and Agents of Disease
18
Portals of entry – characteristic route a microbe follows to enter the tissues of the body
Becoming Established: Phase One – Portals of Entry
• Exogenous agents originate from source outside the body
• Endogenous agents already exist on or in the body (normal flora)
Conjunctiva
Respiratory tract
Gastrointestinal
tract
Pregnancy
and birth
Urogenital tract
Skin
Figure 13.8 Portals of entry
19
– Skin: nicks, abrasions,
punctures, incisions
– Gastrointestinal tract: food, drink, and other ingested materials
– Respiratory tract: oral and nasal cavities
– Urogenital tract : sexual, displaced organisms
– Transplacental
Portals of Entry
20
Pathogens That Infect during Pregnancy
• STORCH - Syphilis, Toxoplasmosis, Other diseases
(hepatitis B, AIDS and chlamydia), Rubella,
Cytomegalovirus and Herpes simplex virus
Maternal blood pools
within intervillous space
(a) (b)
Umbilical
cord
Umbilical
arteries (fetal blood)
Umbilical
vein
Bacterial
cells
Umbilical cord
Maternal
blood vessel
Placenta
Placenta
Figure 13.9 Transplacental infection of the fetus
21
Attaching to the Host: Phase Two
• Adhesion – microbes gain a stable foothold at the portal of entry; dependent on binding between specific molecules on host and pathogen
– Fimbrae
– Flagella
– Glycocalyx
– Cilia
– Suckers
– Hooks
– Barbs
(a) Fimbriae
Bacterial cell
Bacteria
Virus
Spikes
Fimbriae
Capsules
(b) Capsules
(c) Spikes
Host cell
Host cell
Host cell
Figure 13.10 Mechanisms of
adhesion by pathogens
22
Adhesion Properties of Microbes
23
Surviving Host Defenses
• Initial response of host defenses comes from phagocytes
• Antiphagocytic factors – used to avoid phagocytosis
• Species of Staphylococcus and Streptococcus produce
leukocidins, toxic to white blood cells
• Slime layer or capsule – makes phagocytosis difficult
• Ability to survive intracellular phagocytosis
(c) Blocked phagocytic response
Bacteria cannot
be engulfed
Capsule
Phagocyte Continued growth
of microbes damages
host tissue
Blocked
Figure 13.11 Bacteria are able
to escape phagocytosis
24
Invading the Host and Becoming Established: Phase Three
• Some pathogens produce a secretion system to
insert specialized virulence proteins directly into
the host cells
(d) Invasion factors
Adhesion by
fimbriae
Release of
proteins
Disruption of actin
and ruffling
Cell pulled into
vacuole
Systemic
invasion
Loss of
microvilli
Salmonella
multiplies
internally
Salmonella
moves out of
cell into
deeper
tissues
Microvilli
Secretion
system
Pedestal Salmonella
Figure 13.11 Events of Salmonella invasion into the intestine
25
Causing Disease
• Virulence factors – traits used to invade and establish themselves in the host, also determine the degree of tissue damage that occurs – severity of disease
• Exoenzymes – dissolve extracellular barriers and penetrate through or between cells
• Toxigenicity – capacity to produce toxins at the site of multiplication
(a) Exoenzymes – dissolve barriers to
penetrate cells
(b) Toxins – diffuse to target cells,
which are killed
Bacteria
Bacteria Epithelial cell
Cell
cement
Exotoxins
Figure 13.11
26
Bacterial Toxins: A Potent Source of Cellular Damage
• 2 Types of Bacterial Toxins:
– Endotoxin: toxin that is not secreted but is released after the cell is damaged
• Composed of lipopolysaccharide (LPS), part of the outer membrane of gram-negative cell walls
– Exotoxin: toxin molecule secreted by a living bacterial cell into the infected tissue
• Strong specificity for a target cell
• Hemolysins
• A-B toxins (A-active, B-binding)
27
Bacterial Toxins: Exotoxins and Endotoxins
Exotoxins
(a) Target organs are damaged;
heart, muscles, blood
cells, intestinal tract show
dysfunctions.
Endotoxins
(b) General physiological effects–
fever , malaise, aches, shock
Figure 13.12 the
effects of
circulating
exotoxins and
endotoxins
28
13.3 The Outcomes of Infection and Disease
• 4 distinct stages of clinical infections: – Incubation period: time from initial contact with the
infectious agent to the appearance of first symptoms; agent is multiplying but damage is insufficient to cause symptoms; several hours to several years
Height of
infection
Initial
exposure
to microbe Time
Inte
nsit
y o
f sym
pto
ms
Incu
ba
tio
n p
erio
d
Pro
dro
ma
l sta
ge
Pe
rio
d o
f in
va
sio
n
Co
nva
lesce
nt p
erio
d
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
29
The Process of Infection and Disease
– Prodromal stage: vague feelings of discomfort; nonspecific complaints
– Period of invasion: multiplies at high levels, becomes well-established; more specific signs and symptoms
– Convalescent period: as person begins to respond to the infection, symptoms decline
Height of
infection
Initial
exposure
to microbe Time
Inte
nsit
y o
f sym
pto
ms
Incu
ba
tio
n p
erio
d
Pro
dro
ma
l sta
ge
Pe
rio
d o
f in
va
sio
n
Co
nva
lesce
nt p
erio
d Figure 13.14
Stages in infection
and disease
30
Patterns of Infection
• Localized infection – microbes enter the body and
remains confined to a specific tissue
• Systemic infection – infection spreads to several sites
and tissue fluids usually in the bloodstream
• Focal infection – when infectious agent breaks loose
from a local infection and is carried to other tissues
Localized
infection (boil)
Systemic
infection
(influenza)
Focal infection
(a) (b)
(c)
Figure 13.15
Infections with
regard to
location
31
Patterns of Infection • Mixed infection – several microbes grow simultaneously
at the infection site - polymicrobial
• Primary infection – initial infection
• Secondary infection – another infection by a different microbe
Primary
(urinary)
infection
Secondary
(vaginal)
infection Various
microbes
Mixed infection (d)
(e)
Figure 13.15
Infections with
regard to location
32
Patterns of Infection
• Acute infection – comes on rapidly, with severe but short-lived effects
• Chronic infections – progress and persist over a long period of time
33
Signs and Symptoms: Warning Signals of Disease
• Earliest symptoms of disease as a result of
the activation of the body defenses
– Fever, pain, soreness, swelling
• Signs of inflammation:
– Edema: accumulation of fluid
– Granulomas and abscesses: walled-off
collections of inflammatory cells and microbes
– Lymphadenitis: swollen lymph nodes
34
Signs of Infection in the Blood
• Changes in the number of circulating white blood cells – Leukocytosis: increase in white blood cells
– Leukopenia: decrease in white blood cells
– Septicemia: microorganisms are multiplying in the blood and present in large numbers
• Bacteremia: small numbers of bacteria present in blood not necessarily multiplying
• Viremia: small number of viruses present not necessarily multiplying
35
Infections That Go Unnoticed
• Asymptomatic (subclinical) infections –
although infected, the host doesn’t show any
signs of disease
• Inapparent infection, so person doesn’t seek
medical attention
36
The Portal of Exit: Vacating the Host
• Pathogens depart by a specific avenue; greatly influences the dissemination of infection
– Respiratory: mucus,
sputum, nasal
drainage, saliva
– Skin scales
– Fecal exit
– Urogenital tract
– Removal of blood
Skin cells
(open lesion)
Coughing,
sneezing
Urine
Insect bite
Removal
of blood
Feces Figure 13.16 Major portals
of exit of infectious diseases
37
Persistence of Microbes and Pathologic Conditions
• Apparent recovery of host does not always mean the microbe has been removed
• Latency – after the initial symptoms in certain chronic diseases, the microbe can periodically become active and produce a recurrent disease; person may or may not shed it during the latent stage, herpes
• Chronic carrier – person with a latent infection who sheds the infectious agent, HIV
• Sequelae – long-term or permanent damage to tissues or organs, Lyme disease can cause arthritis
38
13.4 Origins and Transmission Patterns of Infectious Microbes
• Reservoir – primary habitat of pathogen in
the natural world
– Human or animal carrier, soil, water, plants
• Source – individual or object from which an
infection is actually acquired
39
Living Reservoirs
• Carrier – an individual who inconspicuously shelters a pathogen and spreads it to others; may or may not have experienced disease due to the microbe
• Asymptomatic carrier – shows no symptoms
• Passive carrier – contaminated healthcare provider picks up pathogens and transfers them to other patients
(c) Transfer of infectious agent through contact Infectious agent
Passive
Figure 13.17 carriers in transmission of
infectious agents
40
Living Reservoirs
• Asymptomatic carrier – shows no symptoms
– Incubation carriers: spread the infectious agent during the incubation period
– Convalescent carriers: recuperating without symptoms
– Chronic carrier: individual who shelters the infectious agent for a long period
(a) (b)
Stages of release during infection
Incubation Convalescent Chronic Asymptomatic
Time
Figure 13.17 carriers in transmission
of infectious agents
41
Animals as Reservoirs and Sources
• A live animal (other than human) that transmits an infectious agent from one host to another is called a vector
• Majority of vectors are arthropods – fleas, mosquitoes, flies, and ticks
• Some larger animals can also spread infection – mammals, birds, lower vertebrates
• Biological vectors – actively participate in a pathogen’s life cycle
• Mechanical vector – not necessary to the life cycle of an infectious agent and merely transports it without being infected
42
• An infection indigenous to animals but naturally
transmissible to humans is a zoonosis
• Humans don’t transmit the disease to others
• At least 150 zoonoses exist worldwide; make
up 70% of all new emerging diseases
worldwide
• Impossible to eradicate the disease without
eradicating the animal reservoir
Animals as Reservoirs and Sources
43
Common Zoonotic Infections
44
The 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
• Highly communicable disease is contagious
• Non-communicable infectious disease does not arise through transmission from host to host
– Occurs primarily when a compromised person is invaded by his or her own normal microflora
– Contact with organism in natural, non-living reservoir
45
Patterns of Transmission
• Direct contact – physical contact or fine aerosol droplets
• Indirect contact – passes from infected host to
intermediate conveyor and then to another host
– Vehicle: inanimate material, food, water, biological
products, fomites
– Airborne: droplet nuclei, aerosols
Marshall W. Jennison, Massachusetts Institute of Technology, 1940
Figure 13.19 a sneeze
46
Figure 13.18 How Communicable Infectious Diseases are Acquired
Communicable
Infectious Diseases
Direct Indirect
(vehicles)
Contact: Kissing,
sex (Epstein-Barr
virus, gonorrhea)
Droplets
(colds,
chickenpox
Vertical
(HIV syphilis)
Biological
Vector (West
nile virus,
malaria
Food, water,
biological products
(Salmonella, E. coli)
Fecal-oral contamination
can also lead to both of
these types of transmission
Droplet
nuclei
Aerosols
Fomites
(Staphylococcus
aurreus)
Air (tuberculosis,
influenza virus
hantavirus)
47
Nosocomial Infections
• Diseases that are acquired or developed during a hospital stay
• From surgical procedures, equipment, personnel, and exposure to drug-resistant microorganisms
• 2 to 4 million cases/year in U.S. with approximately 90,000 deaths
Enterobacter spp. Enterococci
Pseudomonas aeruginosa
Staphylococcus aureus
S. aureus
Coagulase-negative
staphylococci
E. coli
P. aeruginosa
Coagulase-negative
staphylococci
Enterobacter spp.
Enterococci
P. aeruginosa
P. aeruginosa
S. aureus
S. aureus
Acinetobacter spp.
Enterobacter spp.
Klebsiella pneumoniae
Coagulase-negative
staphylococci
Candida spp.
Enterobacter spp.
Enterococci
E. coli
P. aeruginosa
E. coli
Candida spp.
Other
12%
Skin
8%
Blood
6%
Urinary tract
39%
Lower
respiratory tract
18%
Surgical wounds
17%
Figure 13.20
48
Preventing Nosocomial Infections
49
Universal Blood and Body Fluid Precautions
• Stringent measures to prevent the spread of nosocomial infections from patient to patient, from patient to worker, and from worker to patient – universal precautions
• Based on the assumption that all patient specimens could harbor infectious agents, so must be treated with the same degree of care
50
13.5 Epidemiology: The Study of Disease in Populations
• The study of the frequency and distribution of disease and health-related factors in human populations
• Surveillance – collecting, analyzing, and reporting data on rates of occurrence, mortality, morbidity and transmission of infections
• Reportable, notifiable diseases must be reported to authorities
• Centers for Disease Control and Prevention (CDC) in Atlanta, GA – principal government agency responsible for keeping track of infectious diseases nationwide
51
Frequency of Cases
• Prevalence – total number of existing cases with respect to the entire population usually represented by a percentage of the population
• Incidence – measures the number of new cases over a certain time period, as compared with the general healthy population
• Mortality rate – the total number of deaths in a population due to a certain disease
• Morbidity rate – number of people afflicted with a certain disease
52
Epidemiological Data from the CDC Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Infections with the outbreak strain of
Salmonella Typhimurium, by date of illness onset
(n=696 for whom information was reported as of April 20, 9pm EDT)
Number of persons
16
14
12
10
8
6
4
2
0
8/1
5
8/2
9
9/1
2
9/2
6
10
/10
1
0/2
4
11
/7
11
/21
1
2/5
1
2/1
9
1 /
2
1/1
6
1/3
0
2/1
3
2/2
7
3/1
3
3/2
7
4/1
0
4/2
4
Illness that began
during this time may
not yet be reported
2008 2009 Date of illness onset
*Some illness onset dates have been estimated from other reported information
2006 2007 2008 2009
42,000
44,000
46,000
48,000
Incid
ence
Estimated numbers of adults and
adolescents living
With AIDS at the end of 2007 –
United States and dependent areas
AK
HI
Puerto Rico U.S.
Virgin Islands
DC
American
Samoa
Northern
Marina
Islands
Guam
Estimated AIDS cases
1 - 1207
1208 - 3333
3334 - 8855
8856 - 75146
These numbers are point estimates, which result from adjustments for reported case counts. The reported case counts have been adjusted for reporting delays, but not for incomplete reporting. Data source: HIV/AIDS Surveillance Report, 2007. Vol. 19, table 14. Inset maps not to scale.
Data classed using quartiles
TB Case Rates by Age Group
and Sex, United States, 2008
Cases p
er
1,0
0,0
00
10
8
6
4
2
0
<15 yrs 15-24 yrs 25-44 yrs 45-64 yrs ≥65 yrs
Male Female
Reported TB Cases Race/Ethnicity*
United States, 2008
White
(17%)
American Indian or
Alaska Native (1%)
Asian
(26%) Native Hawaiian or
Other Pacific Islander
(<1%)
Hispanic or Latino
(29%) Black or
African-American
(25%)
*All races are non-Hispanic. Persons reporting two or more races
Accounted for less than 1% of all cases
(a) (b)
(c)
53
• Endemic – disease that exhibits a relatively steady frequency over a long period of time in a particular geographic locale
• Sporadic – when occasional cases are reported at irregular intervals
Figure 13.22 Patterns of Infectious Disease Occurrence
(a) Endemic Occurrence (Valley fever)
Outbreaks
(b) Sporadic Occurrence (Measles)
54
• Epidemic –
when prevalence of
a disease is
increasing beyond
what is expected
• Pandemic –
epidemic across
continents
Figure 13.22 Patterns of Infectious Disease Occurrence
(c) Epidemic Occurrence (Syphilis)
(d) Pandemic Occurrence (AIDS)