The contributors :- Robert Koch (1893

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 The contributors :Robert Koch (1893-1910): a German scientist, he isolated
anthrax bacillus from infected cattle in pure culture. In 1884 he
established scientific bases called:
 Koch’s postulates:
a- The organisms should be present in all animals suffering
from the disease & absent in all healthy animal.
b- The organism must be grown in pure culture outside
diseased animal host.
c- When such culture is inoculated in susceptible animal,
this animal must develop the symptom.
d- The organism must be isolated from the experimentally
infected animal & shown to be identically with the
original isolate.
 The host parasite relationship:There are various types of interactions can occur between
diverse microbial populations, or between microbial & plant or
animals.
These interactions include:
 Commensalisms: is a unidirectional relationship between
populations in which one population benefits & the other
one is unaffected; such as one species of organism uses
the body of a larger species as its physical environment.

Synergism: in which both populations benefit from the
relationship but that the association is not obligatory. Both
populations are capable of surviving independently,
although they both gain advantage from the synergistic
relationship.

Mutualism
(Symbiosis):
is
an
obligatory
interrelationship between two populations that benefits
both of them.

Competition: occurs when two populations are striving
for the same resource; often it focuses on a nutrient
present in limited concentrations.

Amensalism

Predation: involves the consumption of a prey species by
(Antagonism):
occurs when one
population produces
a substance inhibitory to
another population. (Ex: production of antibiotic).
a predatory population. The predatory populations derive
nutrition from the prey species.

Parasitism: the parasite population is benefited & the
host population is harmed; parasitic relationships are
characterized by a relatively long period of contact & the
parasite is smaller than the host.
 Epidemiology of Infectious Disease: Epidemiology: This science examines factors involved in the
incidence, spread, prevention & control of infectious &
noninfectious disease.
 Disease outbreaks: A disease outbreak is considered to have
occurred when several case are reported in a relatively short
period of time in a geographically defined area. The study of
outbreaks disease includes:
1) Source of disease outbreaks:
pathogens are transmitted from one infected individual to
another & pathogens can be transmitted directly from one
individual to another or indirectly, by means of another
living agent(vector), or from inanimate source such as food
& water.
2) Reservoirs of pathogens:
The source of an infectious agent is known as the reservoir.
The transmission of infection agents involves the movement
of pathogens from a source to the appropriate portal entry.
* The reservoirs of human pathogens are nonliving sources
such as soil & water
*Animals are sometimes are the reservoirs of human
pathogens & may also be involved in the transmission of
pathogens.
* people infected with a pathogen act as a source of
contagion for others ( the term contagious disease indicates
that a pathogen will move with ease from one individual to
the next).
*Infected individuals do not develop disease symptoms;
called asymptomatic carriers Although they do not become
sick themselves but regard important reservoirs of infectious
agents. There are four types of carriers:
a- Active carrier: person who has an overt clinical case of the
disease.
b-A convalescent carrier: a person who has recovered from the
infectious disease.
c- A healthy carrier: a person has harbors the infectious organisms
but is not ill.
d-An incubatory carrier: person who is incubating the organism in
large number but is not yet ill.
3-The pattern of disease outbreak in community
a- Sporadic disease: the disease which occurs occasionally at
irregular intervals in a human population.
b- Endemic disease: is the disease which maintains a relatively
steady low level frequency at regular interval.
c- Epidemic disease: is a sudden increase in the occurrence of
disease above the expected level.
d- Pandemic disease: it is an increase in disease occurrence
within a large population over a very wide region (usually the
world)
e- Zoonoses: they are infectious disease occur in animals &
occasionally transmitted to human, like brucellosis & rabies.
 Transmission of the infectious agent
1) Airborne transmission: the agent is truly suspended in
the air & travels over a meter or more from the source to
the host, like droplet nuclei or dust.
2) Contact transmission: which mean the coming together
or touching of the source of the infectious disease agent &
the host.
 Direct contact
actual physical interaction with the
infections source (person to person).
 Indirect contact
transmission of the infectious
organism from the source to the host via an intermediate
& often an inanimately object.
3) Vehicle transmission: inanimate object involved in the
transmission of an infectious organism are called vehicles.
In this case a single inanimate vehicle serves to spread the
organism to many hosts but does not support its
multiplication. Ex: surgical instruments, bedding & eating
outside.
4) Vector-borne transmission: living transmitter of an
infectious organisms are called Vector; like insects, ticks,
mite, fleas, dogs, cats, bats,…etc.
 Disease:Is an abnormal condition of living pathology that is a branch
of biology that involves the study of living things in their
abnormal forms & conditions.
 Clinical stages of a disease in host:
A) Acute disease: Is characterized by symptoms that usually
appears quickly & become very intense & then subsides
when the host immune system has overwhelmed the
pathogen or its toxic products. Ex: measles, and mumps.
These acute diseases have 3 stages:
 Incubation period: the period between entrance of pathogen
& appearance of the first symptoms of a disease.
 Acute period: symptoms of the disease are at their peak. Ex:
fever, cough in resp, diarrhea & vomiting in intestinal tract.
 Convalescent period: a period characterized by a sharp
decline in symptoms.
Latent period
decline
Agent enters
healthy body
prodromal stag
First
symptoms of
disease
highly
clinical stage
Characterist
ic symptoms
(peak)
Incubation
stage
B) Chronic disease & persistence: symptoms are expressed
over a long period of time; infectious agent here is an
intracellular parasite like brucellosis & tuberculosis. Some
microorganisms that persist in host, give rise to a mild
symptoms or no symptoms & it’s actively shed from the host
& the M.O may persist in the host for days, months or even
year; like bacteria of cholera, typhoid & diphtheria.
 Types of disease
1)Local: a disease that restricted to a certain area in the body.
2)Focal: localized site of disease from which bacteria & their
products can spread to other body parts.
3)Primary: disease caused by one microbial species.
4)Secondary: a primary disease complicated with second
pathogen.
5)Mixed: disease caused by two or more microorganisms.
6)Sub clinical: that does not give rise to any detectable
manifestation.
7)Latent: disease that persists in the tissue in dormant state &
later becomes manifested usually when the host resistance is
lowered.
 Pathogenicity:-
First sign of
recovery
(disease end)
The ability of M.O to cause disease. Multiple mechanisms
may contribute to pathogenicity, including production of
toxin stimulation of host inflammatory responses.
Pathogenesis of bacterial infection includes initiation of the
infections process & the mechanisms that lead to the
development of signs & symptoms of disease and the
Characteristics of bacteria that are pathogen include:





Transmissibility
Adherence to host cell
Invasion of host cell
Toxigenicity
Ability to evade the host’s immune system

Properties
that
is
essential
for
pathogenicity:1. Transmissibility: The ability to grow or to be shed in body
fluids or secretion. The mode & site of transmission to the
new host include the following :
 Inhalation
 Ingestion
 Injection
 Sexual transmission
 Presence of vector
2. Infectivity: Is the ability of pathogenic M.O to initiate
infection by penetrating the healthy body & overcome the
first lines of defense mechanism. Therefore the infection is
the process by which the parasite enters into a relationship
with the host & this process depended on:
a.
b.
c.
The entrance of the parasite in the host
The establishment & multiplication within the body
The infection process is related to :

Dosage of pathogen

Phase of growth
the log phase are more likely to
over come host resistance than those in latent phase.
3. Virulence: Is the pathogen capacity to harm the host & its
manifestation of complex host parasite relationship. Virulent
organisms exhibit pathogenisity when introduce in very
small number. Virulence is measured in term of the numbers
of M.O or Mgm’s of toxin necessary to kill a given host.
 Virulence might be lost by the following:
 Attenuation
 Loss of capsule
 Colony variation
 Heat & desiccation
 Virulence may be enhanced by:
 Successive passage in lab animals
 Presence with other bacteria ex: C. diphtheria & St.
pyogenes
 Conserving of virulence:
 Lyophilization
 Using enrichment culture media containing blood, store in
dark at low temperature
 Spore forming bacteria
 The microbial factors contributing to infection
(Virulence factors):



1. Extra cellular enzymes:
Collagenase
Protase
Hyaloranidase
Streptokinase
2. Invasiveness: It’s the ability of microorganism to enter host
tissues, multiply & spread.
3. Adherence factors: If the bacteria did not adhere to the cells of
tissue surface, they would be swept away by mucous & other fluids
that bath the tissue surface.
There for several factors play roles in adherence such as :
 Surface hydrophobicity & net surface charge
 Binding molecules on bacteria & host receptor interaction
 Pilli, hair like appendages
4. Antiphagocytic Factors: Some pathogens evade phagocytosis or
leukocytes microbicidal mechanisms by absorbing normal host
components to their surfaces. Ex.: S. aureus has surface protein A,
which bind to the Fc portion of IgG.
5. Intracellular pathogenicity: Some bacteria (e.g.: M. tuberculosis)
live & grow in the hostile environment within poly–morphonuclear
cells, macrophages or monocytes.
6. Antigenic Heterogenecity: such as antigenic shift and drift in
influenza factors.
7. Toxins: The ability of a M.O to produce toxin that contributes to
the development of disease. There are two groups of toxin:
EXOTOXIN
ENDOTOXIN
Excreted by living cell
found in high concentration
in fluid media
Polypeptide with M.W
10000-900000
Relatively unstable toxicity
often destroyed rapidly by
heating over 60 °C
Highly antigenic, stimulate
the formation of titer of
antitoxin
Convert to antigenic non
toxic by using heat,
formalin, acid
Fatal to lab animal in 1 Mg
or less
Integral part of M.O cell
wall in
G –ve bacteria
L.P.S, lipid A is responsible
to toxicity
Relatively stable with stand
heating over 60 °C for hours
Do not stimulate the
formation of antitoxin
Do not convert
Weakly toxic fatal to
animals in 100 Mg/ml
Do not produce fever
Produce fever
A. Gram + cocci
 Staphylococcus :
The genus staphylococcus has at least 30 species. The three
main species of clinical importance are: S. aureus, S.
epidermidis, and S. saprophyticus.
The S. aureus
synthesis of the enzyme coagulase & yellow pigments & cause
sever chronic infections but coagulase –ve such as S.
epidermidis are non pigmented & less invasive.
Morphology & Identification: Staphylococci are spherical cells about 1Mm in diameter
irregular clusters. Single cocci, pairs, tetrads & chains are
also seen in liquid culture.
 Culture of staphylococci : This bacteria grow readily on
most bacteriological media under aerobic condition & at 37
C° but form pigment best at room temperature (2025°C).Colonies on solid media are round, smooth, raised &
glistering. (S. aureus forms gray to deep golden yellow
colonies. S. epidermidis colonies usually are gray to white on
primary isolation; many colonies develop pigment only upon
prolonged incubation).
*Growth characteristics:
Staphylococcus slowly ferments
producing lactic acid but no gas.
many
carbohydrates,
*Antigenic structure:Staphylococcus contains antigenic polysaccharides & protein as
well as other substances important in cell wall structure.
Peptidoglycan & polysaccharide polymer containing linked
subunits provides the rigid exoskeleton of the cell wall. Teichoic
acids, which are polymer of glycerol or ribitol phosphate, are
linked to the peptidoglycan & can be antigenic.
Toxins & Enzymes:Staphylococci can produce disease both through their ability to
multiply & spread widely in tissues & through their production
of many extra cellular substances;
such as:
 Catalase : converts hydrogen peroxide into water &
oxygen.
 Coagulase : clots oxalated or citrated plasma in the
presence of a factor contained in sera. The serum factor
reacts with coagulase to generate both esterrase & clotting
activities in a manner similar to the activation of
prothrombin to thrombin.
 Other enzymes : such as hyaluronidase, staphylokinase,
proteinases, lipases &  - lactomase.
 Exotoxins :  - toxin degrades sphingomyelin.
 Leukocidin : kill exposed white blood cells.
 Toxic shock syndrome toxin
 Enterotoxin
Pathology of S.aureus: The staphylococci produce
disease through their ability to multiply & spread widely in
tissues & also through their production of many extra cellular
substances such as Exotoxins & other enzymes involved in
staphylococcal invasiveness. Staphylococcal lesion is the
furuncle or other localized abscess. Groups of S. aureus
established in a hair follicle lead to tissue necrosis & then the
formation of abscess. S. aureus also causes disease through the
elaboration of toxins, without apparent invasive infection.
Diagnostic laboratory tests:
 Culture S. aureus ferment mannitol & if the specimens
contaminated with a mixed flora can be cultured on media
containing 7-5% Nacl.
 Catalase test
 Coagulase test
 Susceptibility testing
 Serologic & typing tests.
Staphylococcus aureus
 Streptococci
Streptococci are a heterogenous group of bacteria & classify into
1)Streptococcus Pyogenes
2)Streptococcus agalactiae
3) Enterococcus faecalis
4) Streptococcus bovis
5) Streptococcus anginosus
6) Streptococcus pneumonia
7)Viridans Streptococcus
Morphology & Identification
 Typical organisms: individual cocci are spherical or
ovoid & are arranged in chains. The lengths of the chains vary
widely & are conditioned by environmental factors. Some
streptococci elaborate a capsular polysaccharide comparable to
that of pneumococci; most group A, B & C strains produce
capsules composed of hyaluronic acid. The cell wall contains
proteins (M, T, R, antigen carbohydrates (group specific) &
peptidoglycan.
Culture: grow in solid media as discoid colonies & produce
capsular material often give rise to mucoid colonies.
Streptococcus pyogenes colony on Columbia agar with 5%
sheep blood in an aerobic atmosphere enriched with 5% carbon
dioxide are surrounded by a wide zone of beta-hemolysis but
both Streptococcus pneumonia & Viridans Streptococcus are
surrounded by a wide zone of alph-hemolysis.
Growth characteristics: growth & hemolysis are aided by
incubation in 10% CO2 ; grow best at 37°C but enterococci also
grow in high (6.5%) NaCl in (0.1%) methylene blue & in bile
esculin agar.
Antigenic structure:
Several antigenic substances are found, such as:
 Group specific cell wall antigen: this carbohydrate is
contained in the cell wall of many streptococci & forms the
basis of serologic grouping (Lancefield groups A-H, K-U).
 M protein: this substance is a major virulence factor of
group
A S. pyogenes & appears as hair like
projections of the cell wall.
 T substance: this antigen has no relationship to virulence
of streptococci. Unlike M protein, T substance is acid labile &
heat labile.
Toxins & Enzymes:
More than 20 extra cellular products that are antigenic are
elaborated by group A streptococci including the following :
a) Streptokinase: transforms plasminogen of human plasma
into plasmin.
b) Streptodornase: depolymerizes DNA.
c) Hyaluronidase: hyaluronidase splits hyaluronic acid &
aids in spreading infecting M.O (spreading factor).
d) Pyrogenic exotoxins (erythrogenic toxin)
e) Diphosphopyridine nucleotidase: this protein related to
the ability to kill leukocytes.
f) Hemolysins: hemolyze red blood cells in vitro.
The most important member of streptococcus
group are.
1.St. pyogenes (group A, B hemolytic streptococci) is one of the
most
important bacterial pathogens & widely distributed
among humans and causes many disease such as
a) Scarlet fever : these disease results from a throat infection
with a strain of St .pyogenes that produces an erythrogenic or
rash, inducing toxin that causes shedding of the skin. Symptom
after two days of incubation period, ascarlational rash appears
on the upper chest & then spreads to the remainder of body.
b) Streptococcal pharyngitis : it is one of the most common
bacterial infections in human & usually called, strep throat. This
disease is spread via droplets of saliva or nasal secretions. The
incubation period in humans 2 to 4 days. The action of the strep.
bacteria in the throat stimulates an inflammatory response &
inflammatory exudates consisting of cells & fluid deposited in
the surrounding tissue, with discomfort, fever, headache,
redness, edema & enlargement of the lymph node in the throat,
in the absence of complications, the disease is self-limited &
disappears within a week.
c) Post streptococcal disease:
 Rheumatic fever: is an auto immune disease
characterized by inflammatory lesions involving the heart
valves, joints, subcutaneous tissues & CNS. Usually occur after
streptococcal sore throat infections & usually infect children of
age 6-15 years age.
 Glomerulonephritis : is an inflammatory disease of renal
glomeruli & membranous structure within the kidney when the
blood is filtered. Damage probably results from the deposition
of Ag-Ab complex in the glomeruli. The effected person
exhibits edema, fever, hypertension & hematuria, occur after
streptococcal infection. No specific therapy once kidney
damage has occurred.
Diagnostic laboratory tests:
 Culture: blood cultures will grow hemolytic group A
streptococci within hours or a few days. Incubation in 10% CO2
often speeds hemolysis because oxygen that inactivates
streptolysin O.
 Antigen detection tests: by using several commercial kits
are available for rapid detection of group A streptococcal Ag
from throat swabs.
 Serological tests: arise in the titer of Ab to group A
streptococcal Ag can be estimated.
2) Str. pneumonia
Form a small round colony & are  ‫ ــ‬hemolytic on blood agar
growth is enhanced by 5-10% CO2 & it is G+ve diploid found in
the upper respiratory tract. The disease usually occurs only in
the individuals with predisposing factors such as viral infections
of the respiratory tract, physical injury to the tract, alcholism
and diabetis. The pathogenesity is due to the rapid multiplication
of the bacteria in alveolar spaces. The alveoli fill with blood
cells, fluid & become inflamed. The sputum is often rust colored
because the blood is coughed.
Laboratory tests
 Culture: on culture media form a small round colony at
first dome-shaped & later developing a central plateau with an
elevated rim. On blood agar incubation in 10% CO 2 often
speeds  ‫ ــ‬hemolysis.
 Smears: give single cocci or pairs rather than definite
chains or lancet-shaped diplococci.
 Quelling Reaction: when pneumonococci of a certain
type are mixed with specific antipolysaccharide serum or with
polyvalent antiserum on
a microscope slide, the
capsule swells markedly.
 Biochemical reaction: on solid media the growth of
pneumococci is inhibited around a disk of optochin while St.
viridans is not inhibited by optochin.
The pnemococci lyses in a few minutes when exposure to
bile (10%) or sodium deoxycholate (2%) is added to a broth
culture or suspension of organisms at neutral PH.
With age, the organisms rapidly become G -ve & tend to
lyses spontaneously.
capsule
G+ve diploid
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