Stages of Pathogenesis Lec 4

STAGES OF PATHOGENESIS
A generalized sequence of the stages of infection is as follows:

(1) Transmission from an external source into the portal of entry.
(2) Evasion of primary host defenses such as skin or stomach acid.
(3) Adherence to mucous membranes, usually by bacterial pili.
(4) Colonization by growth of the bacteria at the site of adherence.
(5) Disease symptoms caused by toxin production or invasion accompanied by inflammation.
(6) Host responses, both nonspecific and specific (immunity), during steps 3, 4, and 5.
(7) Progression or resolution of the disease.
Pathogen Transmission
An infection starts with exposure to a pathogen. The natural site or
home for a pathogen is known as a reservoir and can either be
animate (human or animal) or inanimate (water, soil, food). A
pathogen can be picked up from its reservoir and then spread from
one infected host to another.
Carriers play an important role in the spread of disease, since they
carry the pathogen but show no obvious symptoms of disease. A
disease that primarily occurs within animal populations but can be
spread to humans is called a zoonosis, while a hospital-acquired
infection is known as a nosocomial infection.
The mechanism by which a pathogen is picked up by a host is referred
to as mode of transmission, with the main mechanisms listed below:
Direct contact
Includes host-to-host contact, such as through kissing or sexual
intercourse, where one person might come in contact with another
person’s skin or body fluids. An expectant mother may transmit a pathogen to her infant by vertical contact while
pregnant, or during the act of giving birth.
Droplet transmission
is often considered to be a form of direct contact as well. It involves transmission by respiratory droplets, where an
infected host expels the pathogen in tiny droplets by coughing or sneezing, which are then inhaled by a host nearby.
These droplets are not transmitted through the air over long distances, nor do they remain infectious for very long.
Indirect contact
Involves the transfer of the infectious agent through some type of intermediary, such as a contaminated object or
person. The pathogen might be deposited on an inanimate object, called a fomite, which is then used by another
person. This could include a shared toy or high-touched surface, like a doorknob or computer keyboard. Alternatively,
a healthcare worked might transmit a pathogen from one patient to another, if they did not change their gloves
between patients.
Airborne transmission
Occurs due to pathogens that are in small particles or droplets in the environment, which can remain infectious over
time and distance. An example might be fungal spores that are inhaled during a dust storm.
Fecal-oral transmission occurs when an infected host is shedding the pathogen in their feces which contaminate food
or water that is consumed by the next host.
Vector-borne transmission
Occurs when an arthropod vector, such as mosquitoes, flies, ticks, are involves in the transmission. Sometimes the
vector just picks up the infectious agents on their external body parts and carries it to another host, but typically the
vector picks up the infectious agent when biting an infected host. The agent is picked up in the blood, and then spread
to the next host when the vector moves on to bite someone else.
Pathogenesis
A microbe that is capable of causing disease is referred to as a pathogen, while the organism being infected is called
a host. The ability to cause disease is referred to as pathogenicity, with pathogens varying in their ability.
An opportunistic pathogen is a microbe that typically infects a host that is compromised in some way, either by a
weakened immune system or breach to the body’s natural defenses, such as a wound. The measurement of
pathogenicity is called virulence, with highly virulent pathogens being more likely to cause disease in a host.
Pathogenesis refers both to the mechanism of infection and to the mechanism by which disease develops. Virulence
is the measure of the pathogenicity of an organism.
- The degree of virulence is related directly to the ability of the organism to cause disease despite host
resistance mechanisms; it is affected by numerous variables such as the number of infecting bacteria, route
of entry into the body, specific and nonspecific host defense mechanisms, and virulence factors of the
bacterium.
- Virulence can be measured experimentally by determining the number of bacteria required to cause animal
death, illness, or lesions in a defined period after the bacteria are administered by a designated route.
Consequently, calculations of a lethal dose affecting 50 percent of a population of animals (LD50) or an
effective dose causing a disease symptom in 50 percent of a population of animals (ED50) are useful in
comparing the relative virulence of different bacteria. Virulence of the pathogen is important, but so is the
number of microbes that gained entry to the host, the location of entry, the overall health of the host, and
the state of the host’s defenses. Exposure to a pathogen does not ensure that disease will occur, since a
host might be able to fight off the infection before disease signs/symptoms develop.
Virulence Factors
In order for a bacterium to be virulent, it must have capabilities that allow it to infect a host. These capabilities arise
from physical structures that the bacterium has or chemical substances that the bacterium can produce.
The genes that code for virulence factors are commonly found clustered on the pathogen’s chromosome or plasmid
DNA, called pathogenicity islands.
- These pathogenicity islands can be distinguished by a G+C content that differs from the rest of the genome
and the presence of insertion-like sequences flanking the gene cluster.
- Pathogenicity islands facilitate the sharing of virulence factors between bacteria due to horizontal gene
transfer, leading to the development of new pathogens over time.
Genes for virulence factors are controlled by quorum sensing, to ensure gene activation when the pathogen
population is at an optimal density. Triggering the genes too soon could alert the host’s immune system to the invader,
cutting short the bacterial infection.

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STAGES OF PATHOGENESIS

A generalized sequence of the stages of infection is as follows:

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