Chapter 13

Microbe-Human Interactions

Infection, Disease, and Epidemiology

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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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

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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

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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

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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

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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

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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

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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

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– 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

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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

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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

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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

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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

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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

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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)

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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

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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.

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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

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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

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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

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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)