Microbe-Human Interactions:

Infection and Disease

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 Infection- a condition in which

pathogenic microbes penetrate host
defenses, enter tissues & multiply

Disease any deviation from health,

disruption of a tissue or organ caused by
microbes or their products

Resident flora
includes bacteria, fungi, protozoa, viruses and
arthropods
most areas of the body in contact with the outside
environment harbor resident microbes; large
intestine has the highest numbers of bacteria
internal organs & tissues & fluids are microbe-free
bacterial flora benefit host by preventing
overgrowth of harmful microbes
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Landscape of the skin

Distribution of flora

Colonized regions of the respiratory

tract

 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
hosts defenses are compromised or when they
grow in part of the body that is not natural to them
Pseudomonas sp & Candida albicans
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Overview of infection

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Portals of entry

skin
gastrointestinal tract
respiratory tract
urogenital tract

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Infectious dose (ID)

minimum number of microbes required for
infection to proceed
microbes with small IDs have greater
virulence
1 rickettsial cell in Q fever
10 bacteria in TB, giardiasis
109 bacteria in cholera

Lack of ID will not result in infection

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Mechanisms of adhesion

fimbrae
flagella
adhesive slimes or capsules
cilia
suckers
hooks
barbs
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Mechanisms of adhesion

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Virulence factors
exoenzymes digest epithelial tissues & permit
invasion of pathogens
Toxigenicity capacity to produce toxins at the
site of multiplication
endotoxins lipid A of LPS of gram-negative bacteria
exotoxins proteins secreted by gram-positive and
gram-negative bacteria

antiphagocytic factors help them to kill or avoid

phagocytes, include leukocidins and capsules
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Avoiding Contact with Phagocytes

Bacteria can avoid the attention of phagocytes in a number of ways.
1.

Pathogens may invade or remain confined in regions inaccessible to

phagocytes. Certain internal tissues (e.g. the lumens of glands, the urinary
bladder) and surface tissues (e.g. unbroken skin) are not patrolled by phagocytes.

2. Some pathogens are able to avoid provoking an overwhelming inflammatory

response. Without inflammation the host is unable to focus the phagocytic defenses.
3. Some bacteria or their products inhibit phagocyte chemotaxis. For example,
Streptococcal streptolysin (which also kills phagocytes) suppresses neutrophil
chemotaxis, even in very low concentrations. Fractions of Mycobacterium
tuberculosis are known to inhibit leukocyte migration. The Clostridium toxin also
inhibits neutrophil chemotaxis.
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4.

Some pathogens can cover the surface of the bacterial cell with a component
which is seen as "self" by the host phagocytes and immune system. Such a
strategy hides the antigenic surface of the bacterial cell. Phagocytes cannot
recognize bacteria upon contact and the possibility of opsonization by
antibodies to enhance phagocytosis is minimized.

For example, pathogenic Staphylococcus aureus produces cell-bound coagulase and

clumping factor which clots fibrin on the bacterial surface. Treponema pallidum, the
agent of syphilis, binds fibronectin to its surface. Group A streptococci are able to
synthesize a capsule composed of hyaluronic acid. Hyaluronic acid is the ground
substance (tissue cement) in connective tissue. Some pathogens have or can deposit
sialic acid residues on their surfaces which prevents opsonization by complement
components and impedes recognition by phagocytes.

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Inhibition of Phagocytic Engulfment

Some bacteria employ strategies to avoid engulfment (ingestion) if phagocytes do make
contact with them. Many important pathogenic bacteria bear on their surfaces
substances that inhibit phagocytic adsorption or engulfment. Clearly it is the bacterial
surface that matters. Resistance to phagocytic ingestion is usually due to a component
of the bacterial cell surface (cell wall, or fimbriae, or a capsule). Classical examples of
antiphagocytic substances on bacterial surfaces include:
1. Polysaccharide capsules of S. pneumoniae, Haemophilus influenzae,Treponema
pallidum and Klebsiella pneumoniae
2. M protein and fimbriae of Group A streptococci
3. Surface slime (polysaccharide) produced as a biofilm by Pseudomonas aeruginosa
4. O polysaccharide associated with LPS of E. coli
5. K antigen (acidic polysaccharides) of E. coli or the analogous Vi
antigen ofSalmonella typhi
6. Cell-bound or soluble Protein A produced by Staphylococcus aureus.
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Survival Inside of Cells

Some bacteria survive inside of phagocytes, either neutrophils or macrophages.

Bacteria that can resist killing and survive or multiply inside of phagocytes or other
cells are considered intracellular parasites.
The intracellular environment of a phagocyte may be a protective one, protecting the
bacteria during the early stages of infection or until they develop a full complement of
virulence factors.

The intracellular environment also guards the bacteria against the activities of
extracellular bactericides, antibodies, drugs, etc.
Some bacteria that are intracellular parasites because they able to invade eukaryotic
cells are listed in Table 1.

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Table 1. BACTERIAL INTRACELLULAR PATHOGENS

Organism

Disease

Mycobacterium tuberculosis

Tuberculosis

Mycobacterium leprae

Leprosy

Listeria monocytogenes

Listeriosis

Salmonella typhi

Typhoid Fever

Shigella dysenteriae

Bacillary dysentery

Yersinia pestis
Brucella species

Plague

Legionella pneumophila

Pneumonia
Typhus; Rocky Mountain Spotted
Fever
Chlamydia; Trachoma

Rickettsiae
Chlamydia

Brucellosis

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Patterns of infection
Mixed infection several microbes grow
simultaneously at the infection site
Primary infection initial infection
Secondary infection another infection by a
different microbe

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 Sign objective evidence of disease as

noted by an observer
Symptom subjective evidence of disease
as sensed by the patient

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Portals of exit

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Portals of exit

Respiratory, saliva
Skin scales
Fecal exit
Urogenital tract
Removal of blood

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Epidemiology
The study of the frequency and distribution of
disease & health-related factors in human
populations
Surveillance collecting, analyzing, & reporting
data on rates of occurrence, mortality, morbidity
and transmission of infections
Reportable, notifiable diseases must be reported to
authorities
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 Centers for Disease Control and Prevention

(CDC) in Atlanta, GA principal
government agency responsible for keeping
track of infectious diseases nationwide
http://www.cdc.gov

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 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
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 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

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MORTALITY: TEN (10) LEADING CAUSES

NUMBER AND RATE/100,000 POPULATION
Philippines
5-Year Average (2004-2008) & 2009
5-Year Average
(2004-2008)
CAUSES
Number
Rate
Number

2009*
Rate

1. Diseases of the Heart

82,290

94.5

100,908

109.4

2. Diseases of the Vascular System

55,999

64.3

65,489

71.0

3. Malignant Neoplasms

43,185

49.6

47,732

51.8

4. Pneumonia

35,756

41.1

42,642

46.2

5. Accidents**

34,704

39.9

35,990

39.0

6. Tuberculosis, all forms

25,376

29.2

25,470

27.6

7. Chronic lower respiratory diseases

20,830

24.0

22,755

24.7

8. Diabetes Mellitus

19,805

22.7

22,345

24.2

9.Nephritis, nephrotic syndrome and

nephrosis

11,612

13.4

13,799

15.0

10. Certain conditions originating in the

perinatal period

12,590

14.5

11,514

12.5

Note: Excludes ill-defined and unknown causes of mortality

* reference year

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MORBIDITY: 10 Leading Causes, Number and Rate

Diseases

2010*
Number

Rate

1. Acute Respiratory Infection

**

1,289,168

1371.3

2. Acute Lower Respiratory

Tract Infection and Pneumonia

586,186

623.5

3. Bronchitis/Bronchiolitis

351,126

373.5

4. Hypertension

345,412

367.4

5. Acute Watery Diarrhea

326,551

347.3

6. Influenza

272,001

289.3

7. Urinary Tract Infection**

83,569

88.9

8. TB Respiratory
9. Injuries
10. Disease of the Heart

72,516
51,201
37,589

77.1
54.5
40.0

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 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
Epidemic when prevalence of a disease is
increasing beyond what is expected
Pandemic epidemic across continents
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Patterns of disease occurrence

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Reservoirs of infection
Primary habitat in the natural world from which a
pathogen originates
Living reservoirs may or may not have symptoms
Asymptomatic carriers
Passive carriers
Vectors live animal that transmits infectious disease

Nonliving reservoirs soil, water

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Types of carriers

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Vectors

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Patterns of transmission
Direct contact
Indirect contact
Vehicle inanimate material, food, water,
biological products, fomites
Airborne droplet nuclei, aerosols

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Nosocomial infections
Diseases that are acquired during a hospital
stay
Most commonly involve urinary tract,
respiratory tract, & surgical incisions
Most common organisms involved gramnegative intestinal flora, E. coli,
Pseudomonas, Staphylococcus
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Nosocomial infections

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Kochs postulates
1. Find evidence of a particular microbe in every
case of a disease
2. Isolate that microbe from an infected subject and
cultivate it artificially in the laboratory
3. Inoculate a susceptible healthy subject with the
laboratory isolate and observe the resultant
disease
4. Reisolate the agent from this subject
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