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Transcript
College of Medicine
Microbiology
Medical Virology
Viral pathogenesis and infection:
Dr. Jawad Kadhim Tarrad
-------------------------------------------------------------------------------------------Pathogen: any organism or causative agent can be cause disease in human
or other organisms. It is classified into two broad groups: primary pathogen
is potential (frank) microbial pathogen has ability to cause infection in health
human, whereas secondary pathogen is opportunistic pathogen has ability to
cause disease in the patient with low defense.
Pathogenicity : it is ability of microbe to cause disease.
Virulence: it is referred to degree or intensity of ability of microbe to
produce disease. The virulence is determined by virulence factors, therefore
some microbes are highly pathogenic, whereas others are low pathogenic
dependent on type of virulence factors.
Virulent pathogen is determined by type of virulence factors that
facilitating pathogenicity:
 Virulence factors mediating adherence of microorganism to
host tissue.
 Virulence factors mediating invasion of organism to host
tissues.
 Virulence factors mediating avoidance of host defense
mechanisms.
 Virulence factors mediating damage host tissues.
The disease is impairment of normal state of organism or any of its
components that hinders the performance of vital functions. It response to
environmental factors (eg; malnutrition, climate, industrial hazard), specific
infectious agents, inherent defect of body or combination of these. The
disease term include infectious diseases and non-infectious diseases.
Infection is presence and multiplication of pathogenic microbe within
human body, and cause symptoms of infection. The infection differs from
other diseases is that caused by living microbial pathogens.
Infection (or not) is determined by balance between number and virulence of
microbe and competency of that host defense. If microbes are overcome, the
disease results. Outcome of most host-parasite relationship is dependent on
three main factors ;
a. Number of pathogenic microorganism infecting the host(dose).
b. Degree of pathogenicity of organism(virulence).
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c. Degree of host defense (resistance).
The infectious disease equation:
Number of organisms(dose) x Virulence
= Infectious
Disease
Host resistance
The infection does not arise in vacuum. It results from interaction of several
factors. The predisposing factors(risk factors) that involved in the
development of infections include mainly three factors:
a. Virulent microbe.
b. Susceptible host.
c. Environmental factors.
Stages of infection:
1. Encounter of microbe with susceptible host.
2. Entry and adhere to susceptible host tissues.
3. Multiply and spread to adjacent cells or to specific cells.
4. Evade host defense mechanism.
5. Damage the host tissues and disease symptoms.
6. Progression or resolution of the disease.
7. Shedding of microbial pathogen into atmosphere.
Sources of infection:
Microorganisms can be found in nearly every environment in nature. There
are many sources of pathogens, some of these pathogens are
indigenous(native resident) to particular environment, other pathogens are
introduced into environment via anthropogenic activities ,or the environment
acts as a vehicle for transport of pathogen from one to another location.
Main sources of infection are ;
1. Human : is common source of infection from patients or carriers.
The carrier is person recovered from disease but harboring pathogenic
organism in his body. Fomites are inanimate objects of patients that
may be contaminated and serves as source of pathogenic organisms.
The infectious agent is transmitted from person to person by various
ways such as direct contact, kissing, inhalation of aerosols, faecaloral, venereal contact, blood transfusion and arthropod-spread
(arthropod-borne infection).
2. Animals ; are important source of pathogenic organisms that infect
human. The animals can be serve either the source (reservoir )or
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made transmission (vector)of certain organism. The organisms can
be transmitted from infected animals to human when direct contact
with animals, and handling or consumption of their products(so called
animal-borne infection) or transmitted indirectly by bite of
vectors(arthropod-borne infection). The disease that result is called
zoonosis.
3. Food: the foods are most important media for surviving and
transporting the pathogenic microorganisms and therefore act as main
source of infection eg. Staphylococcal food poisoning. Transmission
of organisms from food to human during feeding or food handling,
therefore called food-borne infection.
4. Water: many pathogenic microorganisms such as Vibrio cholerae ,
E.coli, some protozoa , hepatitis virus , may be found in water. The
infectious agents are transmitted to human by consumption of water or
when swimming in it( so called water-borne infection).
5. Soil: is considered as mother of microorganisms because it has all
types of microorganisms. The infectious disease agents are
transmitted to human through direct work with soil that contain
infectious agents or inhalation of dust .
6. Air: the air we inhale contain millions of suspended particles,
including microorganisms. These particles bearing microorganisms
are released into general environment are called air-droplets
nuclei(which contain microorganisms), therefore act as air-borne
infection.
Portals of entry(routes of infection) :
Major:
1. Respiratory tract(nose).
2. Elementary tract(mouth).
3. Skin, non-intact.
4.Genital tract(vagina).
Mode of transmission:
Minor :
1.Eye
2. Anus
3. Ear canal
4. Urethral canal.
 Most infections (not all) are communicable(transmissible) capable
of spreading from person to person, but some are not communicable
eg. Botulism and Legionella pneumonia. If a disease is highly
communicable, the term contagious is applied.
 The infectious agent is transmitted from source of infection to human
either by vector (entity living such as insects, ticks and mite), or by
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vehicles (entity non-living such as water, food, air, medical devices
and various other inanimate objects).
 The infection is occurring or acquired from hospital, called hospitalacquired infection(nosocomial infection). The infection obtained
from outside the hospital among human community, called
community-acquired infection. The subsequent infection by same
organism in same patient is called re-infection. The infection caused
by endogenous microorganism that already found as part of normal
flora in human body is called self infection(autoinfection). The
infection caused by microorganism originated from external source
(exogenous)either from other infected person(named cross infection)
or from inanimate sources as food or water ( this named
environmental infection).
 The infection may caused by multiple pathogenic microbes( mixed
infection), if high severity is known (super-infection). Some
pathogens can not cause disease without other pathogen(helper) so
called co-infection. When host defenses is low due to pre-existing
infectious disease, a new organism may set-up an infection(secondary
infection).
Horizontal transmission:
 Inhalation: the pathogenic agents may be transmitted by inhalation of
respiratory secretions (air droplet nuclei containing infectious agents)
of infected patients, or by inhalation of contaminated dust (air borne)
with pathogenic microbe.
 Ingestion: the infectious agents can be transmitted by consumption
(during eating or drinking) of contaminated food or water.
 Skin : any small break, abrasion, and wound in skin that permit initial
entry. The transmission may occur through direct contact(such as
handshaking, kissing)with infected person , infected animal or during
handling of fomites of patients, or the organism is transmitted
indirectly by vector bite .
 Blood transfusion: some pathogenic microorganisms can be
transmitted by blood transfusion. Injection of needles during
intravenous drug use or indwelling catheter, have role in transmission.
 Sexual intercourse: certain pathogenic microorganisms can be
transmitted by sexual contact in homosexual or heterosexual persons.
4
Vertical transmission:
The pathogen can transmitted from infected mother to her fetus ;
 Across the placenta (prenatal) ,or
 At time of delivery from birth canal (perinatal), or
 During breast feeding (postnatal) .
Adherence of virus to target cell:
 The viruses tend to exhibit cell and organ specificities. The viral
affinity(tropism) for specific body tissue is dependent on :
1. Presence of specific cellular receptors on cell surface which
interact with virus, and initial infection.
2. the host cell must be provide suitable condition and support
replication of virus. These condition like physical barriers, local
temperature, pH, and other factors are very important in tissue
tropism.
 The presence of cellular receptors and environmental factors as well
as initial location and other conditions on tissue can determine which
part of human body is infected .
Invasion of host tissues(replication and dissemination):
 The viruses replicate either at site of entry or at site distant from their
point of entry. In other word, the viral infections are either localized
on the portal of entry or spread systemically through the body.
 After primary replicate at site of entry, the virus may remains
localized or spread within body of the host from local replication to
target cells . Mechanism of viral spread vary, the most common route
is via blood stream, lymphatics or nerves. The presence of virus in
blood stream is called viremia.
Evasion of host defenses:
The viruses when meet the host cell faced several antimicrobial defenses
of host. The viruses have many mechanisms to avoid action of host
defenses:
 Virokines: Certain viruses encode some proteins act as receptors for
immune mediators such as interferon (IFN) and tumor–necrosis
factor (TNF). When the virus released from virus-infected cell , these
proteins bind to immune mediators and block their ability to interact
with receptor on their intended target. Because reducing host defense,
the virulence of virus is enhanced. These virus-encoded proteins that
block host immune mediators are called cytokines decoys.
5
 Multi-serotypes: Certain viruses have multiple serotypes. The
patient can be infected with one serotype , recover , and have
antibodies that protect from infection by that serotype in future ,
however , that person can be infected by other serotypes of virus.
Most viruses have one serotype , but certain have several serotypes
such as rhinovirus which has more than 100 serotypes , this is the
reason why the common cold by this virus is common.
 Antigenic variation may occur in certain viruses have multiple
antigenic types such influenza virus undergo changes in surface
antigens.
 Certain viruses are able to thwart immune defenses for numbers of
reasons such as latent or can infect cell for long period without
adverse effects on cell.
 Certain viruses are spread from cell to cell without exposed to
immune system. They don’t form extracellular phase.
Damage of host cell:
The time between exposure to virus and onset of disease is called
incubation period, it required to produce sufficient numbers of virus that
lead to cause disease. This period reflects the time needed for the infectious
agents to overcome early defense and grow to a population size.
The mechanisms of viral diseases are various:
1. Most viral diseases are result in host cell death by several
mechanisms:
 Shutoff macromolecules synthesis of host cell.
 Lyses of the cell membrane by lysozymes during viral replication.
 Induction of programmed cell death (suicide program, apoptosis)
by some viruses (eg: HIV, HSV).
2. The pathogenesis may result from immunological attack: for example,
 The hepatitis viruses don’t cause a cytopathic effect in liver cells ,
but the damage of hepatocytes is result of recognition of viral
antigens on hepatocyte surface by cytotoxic T-cell.
 Damage caused by immune response of host to infection, the
response is often which leading to harmful outcome for host such as
hypersensitivity and autoimmune.
In briefly ,the infection result from two effects:
1. Effect of virus replication on host cell.
2. Effect of immune response on virus and host cell.
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Outcome of infection:
 If the host defenses overcome the virulent virus in first step, the
disease is not occurring.
 If viral pathogens overcome the defenses of infected individual,
the disease resulted and it may progress to cause death of
infected host.
 If the host defenses overcome the virulent microbe after
infection, this lead to repair and healing, and recovery from
infection.
 If the host defense is failure to eliminate the microbe from the
body, the infection may become chronic(persistent infection),
which mean the microbes may continues to multiple and
produce significant symptoms of disease for long period.
Persistent viral infection:
Three types of persistent viral infections:
1. Chronic infection: certain patients who have infected with
some viruses continue to produce significant symptoms of
disease and significant amount of virus for long period.
2. Latent infection: certain patients recover from initial infection
and virus production stops. But the patients harboring the virus
in their bodies (remain as carriers) without produce symptoms.
3. Slow virus infections: some infections require to long period
between initial infection and onset of disease, which are usually
measured in years (such as Kuru disease, and HIV).
Virus shedding:
This stage of viral pathogenesis is occurring in any time of infection. The
shedding usually occurs from the body of patient into environment through
portals of exist. The shedding occurs at different stages of disease dependent
on particular agent involved.
Portals of exit :
1. Respiratory tract during coughing and sneezing.
2. GIT through feces and saliva.
3. Genitourinary tract by urine and vaginal secretions.
4. Skin.
5. Blood.
6. Biting arthropods , needle and syringes.
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