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• This is a broad topic that will give you a foundation on how pathogens
cause infections.
• It include the following subtopics:
Mechanisms of microbial dieases A. Establishment of infection (topic 5)
B. Bacterial pathogenesis (topic 6)
C. Viral pathogenesis (topic 7)
D. Fungal pathogenesis (topic 8)

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Learning outcomes

• It the end of this lecture, students should be able to:

a) Define important terms of infections.
Establishment of Infection
b) Describe events involved in the process of establishment of infection.
Topic 5 c) Explain how pathogens breach host defences to establish infections.

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Events in the establishment of infection 1) Encounter or Transmission

1) Encounter or transmission: • Human beings may for the 1st time encounter pathogens while
- The agent meets the host developing in the placenta.
2) Entry or portal of entry: • These pathogens cause congenital infections e.g. rubella, syphilis, HIV
- The agent enters the host and cytomegalovirus.
3) Spread/dissemination: • Some human beings may for the 1st time encounter
- The agent spreads from the cite of entry pathogens/microorganisms during delivery.
Example?
4) Multiplication:
- The agent multiplies in the host. • Some human beings may for the 1st time encounter
pathogens/microorganisms during breastfeeding
5) Damage: Example?
- The agent, the host response or both cause tissue damage.
• Majority of us encounter pathogens/microorganisms for the 1st time
6) Outcome: from the environment (after birth)
- The agent or the host wins out, or they learn to coexist. Example?
7) Exit from the host and survive long enough to be transmitted to another • The source of a pathogen in the environment is known as a reservoir.
host (transmissibility) 5 6

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Reservoirs of Pathogens Types of carriers

• Reservoir – primary habitat of pathogen in the natural world.
• Potential reservoirs include human or animal carrier, soil, water and
plants.
• Source – individual or object from which an infection is actually acquired.
Human Reservoirs
• A sick person is a reservoir for the pathogens causing the infection and
will continue to be a reservoir for as long as the infection continues.
• A such reservoir is called a carrier.
• Carrier is an individual who inconspicuously shelters a pathogen and
spreads it to others.
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a) Asymptomatic carrier – (give a general definition)
• Categories of asymptomatic carriers include:
i. Incubation carriers – spread the infectious agent during the
incubation period
ii. Convalescent carriers – recuperating without symptoms
iii. Chronic carrier – Individual who shelters the infectious agent for a
long period
b) Passive carrier (give a general definition)
– contaminated healthcare provider picks up pathogens and transfers
them to other patients

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.
• Diseases that are transferred from animals to humans are called
zoonotic diseases e.g. rabies and Lyme disease.

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Nonliving Reservoirs
Examples of Zoonotic Diseases • Water, soil and air.
Water
• Poor sanitation and personal hygiene result in the faecal contamination
of water.
• Water is the key component of faecal-oral contamination.
• Examples: Typhoid and cholera
Soil
• It is a normal habitat for many microorganisms.
• Example: Tetanus
Air
• Not habitat but holds pathogens in droplets or aerosol forms.
11 • Example: Diphtheria, corona, TB, pneumococcal pneumonia, HiB 12

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oThrow-back: slide 6
• Some microorganisms that human beings encounter during and after
birth may cause diseases while others will not cause diseases.
• Those that will not cause disease but reside in or on the human body
are known as microbiota or commensals or normal flora.
Microbiota or normal flora or commensals
• Refers to microorganisms residing in or on the body that are not in the
process of causing disease.
• Two types of microbiota:
i. Core microbiota: Always present and carry out known functions in
body ecosystem.
ii. Transient microbiota: Presence is variable e.g. coming and going
meningococcus and pneumococcus of a person’s throat.
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• What parts of the body are typical sites for microbiota?
- Skin, respiratory tract, digestive tract and genitourinary system (urethra,
penis and vagina).
• What is the role of the normal microbiota?
i. Immune stimulation: generates antibodies that are important as first line of
defence.
ii. Keeping out invaders (colonization resistance): Out competes pathogens.
iii. Plays a role in human nutrition and metabolism: play a role in metabolism
of butyrate, bile acids and synthesis of vitamin K.
iv. Conversation of ingested compounds: Detoxifies some potential
carcinogens by degrading them e.g. nitrosamines and heterocyclic amines.
v. Source of infection: Can cause infections e.g. bacteroides from GIT can
produce abscess via trauma, Staphylococcus from skin, Streptococcus
from throat and Streptococcus epidermidis from skin can cause
bloodstream infections and E. coli from GIT can cause UTI infection.
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15 Jawetz, Melnick & Adelberg’s Medical Microbiology, 26 th Edition, page 166 16

oThrow-back: slides 6 - 14
• Some microorganisms that human beings encounter during and after
birth may cause microbial diseases.
• It is evident that microbial diseases are contracted in two general ways:
i. Endogenously and
Lansing M. Prescott, Microbiology, 5th
Edition, Chapter 31, page 700.
ii. Exogenously

Endogenously acquired diseases

• Endogenously acquired diseases are caused by microorganisms
present in or on the body (microbiota).
• Example: a cut can lead to production of pus caused by Staphylococci
that inhibit healthy skin.
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Examples of encounters and disease prevention

o
Type of Example Type of Source Strategy for Preventive
contact agent prevention aim
Exogenously acquired diseases Inhalation Common Virus Respiratory Mask and Barriers
• These diseases result from encounters with pathogens in the cold droplets hand against
environment. hygiene droplets
• Humans acquire disease causing pathogens from the environment Ingestion Typhoid Bacterium Water, food Sanitation Lower
through: food, water, air, objects insect bites, human or animals. fever infecting
dose
• Example: pathogens are transmitted among humans through sneezing,
touching and sexual intercourse. Sexual Gonorrhoea Bacterium Person Protected Avoid
contact sex contact
• The way a pathogen is transmitted suggests a mode of prevention.
Wound Surgical Bacteria Normal Aseptic Avoid
infections microbiota techniques contact

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Mechanisms of transmission of exogenously acquired i) Contact transmission

diseases
• In this mechanism, healthy person is exposed to pathogens by either
touching or being close to an infected person or object.
• There are three mechanisms that can be used to transfer infectious
organisms from reservoir to humans are: • It is subdivide into three types: direct, indirect, and droplet.
i. Contact transmission
Direct contact transmission
ii. Vehicle transmission, and • It does not have an intermediary between the infected person and the
uninfected person.
iii. Vector transmission • This mechanism encompasses such things as touching, kissing, and
sexual interactions.
• The diseases transmitted through direct contact include hepatitis A,
smallpox, staphylococcal infections, mononucleosis, and of course
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sexually transmitted diseases. 22

Indirect contact transmission

• It occurs through intermediates that are usually nonliving articles, such
as tissues, handkerchiefs, towels, bedding, and contaminated needles,
the latter easily transferring HIV and hepatitis B.
• The non-living intermediates that act as the agents of transmission by
indirect contact are known as fomites.

Droplet contact transmission

• It is seen in the transfer of respiratory diseases such as influenza and
whooping cough. Droplet transmission can occur through sneezing,
coughing, and even laughing.
• Although it is confined to short distances, the size of the droplet is
important - The smaller the droplet, the more dangerous it is as an
agent of disease.
• Give examples of pathogens transmitted through this mechanism. 23 24

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iii) Vector transmission

ii) Vehicle transmission
• It involves pathogens “riding” along on supposedly “clean” components.
• For example, food can carry pathogenic organisms and is therefore
considered a vehicle of disease transmission.
• Other possible vehicles are water, air, blood, body fluids, drugs, and
intravenous fluids given to a hospitalized patient.
• Assignment: Give examples of pathogens transmitted by each vehicle
mentioned above.
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• In this mechanism, pathogens are transmitted to a healthy person by a
carrier known to be associated with some disease.
• Vectors that can be used for disease transmission are usually
arthropods, such as fleas, ticks, flies, lice, and mosquitoes.
• There are two ways in which this type of transmission occurs:
mechanical and biological.
• In mechanical vector transmission, the vector’s body parts are
contaminated with the infecting microorganisms e.g. houseflies
• Biological vector transmission occurs through a bite, as seen with, for
instance, the fleas that had a primary role in the transmission of
Yersinia pestis; ticks, which can transmit Borrelia burgdorferi (the
causative agent of Lyme disease); and mosquitoes, which carry West
Nile virus.
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2) Entry or Portal of Entry

• Portal of entry is any point at which organisms can enter the human
body.
• There are three categories of portals of entry in humans:
i. Mucous membranes
ii. Skin, and
iii. Parenteral routes
• The skin and mucous membranes are in direct contact with the exterior
environment and are therefore in close proximity to potential pathogens.
Pathogens enter without crossing the epithelial barriers.
• In contrast, pathogens that enter the body via the parenteral route take
advantage of breaks in the body’s barriers to gain access. Pathogens
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enter into tissues after crossing epithelial barriers. 28

Portals of entry

(i) Mucous Membranes

• Recall from your studies of anatomy that mucous membranes are
located in areas of the body that are adjacent to the outside world.
• These membranes are found in the respiratory tract, the
gastrointestinal tract, and the genitourinary tract.

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(a) The respiratory tract (b) The gastrointestinal tract

• The respiratory tract facilitates
entry through breathing.
• Organisms can be found on
droplets of moisture in the air and
even on dust particles.
• Examples of diseases that use
this portal of entry: colds,
pneumonia, tuberculosis,
influenza, measles, and smallpox
Mucous membranes of the upper respiratory tract
are portals of entry for potential pathogens
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• This system is also open to the
outside world.
• Organisms can enter the body via
the foods and liquids we eat and
drink.
• It is known as the fecal–oral route
of contamination.
• It has a major role in many
infections, especially with Gram-
negative bacteria and viruses.
• Some non-food/water pathogens
require it - polio virus and
hepatitis A virus. 32

(c) The genitourinary tract Genitourinary portals of infection. Panel a: The male urinary and reproductive tract.
Panel b: The female reproductive and urinary tract.
• The urinary and reproductive tracts are also open to the outside world.
• But unlike the respiratory and gastrointestinal tracts, they are more
complicated with respect to entry.
• Urinary tract infections are more common in women than in men. This is
because of the anatomical relationship between the anus and urethra,
which is much closer in women than in men. Because fecal material
contains bacteria, it is easy for these organisms to find their way to the
urinary tract.
• Diseases of the reproductive tract are usually sexually transmitted and
occur as a result of either abrasions or tiny tears in the tissues that
routinely occur during sexual activity.
• Once the mucous membrane barrier is broken, pathogens gain entry.
• Conditions such as syphilis, gonorrhea, chlamydia, herpes, genital warts,
and HIV infections are caused by pathogens that use this portal of entry. 33 34

Portals of entry for some common pathogens

Skin and parenteral route

• The skin is literally covered with many types of microorganism and

easily accessible to many other types, including pathogens.
• Movement of organisms past the barrier of the skin requires a break in
the barrier, and the portal of entry referred to as the parenteral route.
• Things such as injections and insect bites can easily become parenteral
portals of entry any time.

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3. Spread (dissemination) • Spread of a pathogen is influenced by 2 factors:

oAnatomical factors
• Prior to spread, there are 2 possibilities:
oMicrobial factors
i. Upon entry, a pathogen may undergo primary replication at the site of
entry followed by spread e.g. Staphylococcus that infects a cut must
multiply locally before spreading to distant sites. a) Anatomical factors
ii. Upon entry, a pathogen may directly spread in the whole body before • Knowledge of human anatomy helps us to understand infectious
causing a disease e.g. rabies virus, Hepatitis A virus and Rubella virus. diseases.
• In either case, the pathogen must first overcome host defences. • Examples:
• How pathogens overcome host defences was taught in immunology i. Bacterial abscess of the lung (localized infection).
(year 1). oThe abscess could burst and allow the organisms to escape into the
• Assignment: bronchial tree, or, if the abscess is pointed outward, to the pleural
cavity.
oSpread in one or the other direction has different consequences –
37 pneumonia and pleuritis or empyema. 38

ii. Infection of the middle ear. b) Microbial factors

oCommon in children. Why?
oThe eustachin tubes of children do not drain as well as those of adults.
iii. Fluid dynamics
oInfected fluids in the interior of the body tend to flow along fascial planes.
oWhat are fascial planes?
oBody fluids: pleural fluid in pleura cavities, pericardial fluid in the cardiac
sac, synovial fluid in joints, peritoneal fluid in the peritoneal cavity, blood,
lymph, cerebrospinal fluid, urine and aqueous humor of the eye.
oExample: infection of one site of the minges will result in generalized
meningitis because there are no barriers to impede the spread of the
infected cerebrospinal fluid.
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• Bacteria will swim randomly or in response to chemotactic signals.
• Some pathogens will produce chemicals which will facilitate their
movement. Examples:
i. Hydrolases that will pathogens (bacteria or fungi) to break out of the
walled defences erected by the inflammatory response.
ii. Protease that break up fibrin.
iii. Hyaluronidase that hydrolyzes the hyaluronic acid of connective
tissue and allow the spread of pathogen.
iv. Deoxyribonuclease that reduces the viscosity of pus caused by
release of DNA from lysed white cells. Some bacteria make elastases,
collagenases and other powerful proteases.
v. Fungi that cause athlete’s foot make keratin-hydrolysing enzymes that
help them spread through the horny layers of the skin. 40

4. Multiplication
• Pathogen multiplication is directly related to manifestations of
disease/symptoms.
• Pathogens multiple to achieve minimum cells required to initiate an
infection. This number is called infectious dose (ID).
• Lack of ID will not result in infection.
• Multiplication leads to five stages of infection.
i. The incubation period
ii. The prodromal period
iii. The illness period
iv. The decline period
v. The convalescence period
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i. Incubation period ii. Prodromal period

• The incubation period occurs after the initial entry of the pathogen into
the host when it begins to multiply, but there are insufficient numbers of
the pathogen present to cause signs and symptoms of disease.
• Incubation periods can vary from a day or two in acute disease to
months or years in chronic disease, depending upon the pathogen.
• Factors involved in determining the length of the incubation period are
diverse and can include virulence of the pathogen, strength of the host
immune defenses, site of infection, and the amount of the pathogen
received during exposure.
• During this incubation period, the patient is unaware that a disease is
beginning to develop.
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• The prodromal period occurs after the incubation period.
• During this phase, the pathogen continues to multiply, and the host
begins to experience general signs and symptoms of illness caused
from activation of the nonspecific innate immunity, such as not feeling
well (malaise), low-grade fever, pain, swelling, or inflammation.
• These signs and symptoms are often too general to indicate a particular
disease is occurring.
iii. Acute phase
• Following the prodromal period is the period of acute illness, during
which the signs and symptoms of a specific disease become obvious
and can become severe.
• Pathogens multiply at high levels.
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• This period of acute illness is followed by the period of decline as the

immune system overcomes the pathogen.
• The number of pathogen particles begins to decline and thus the signs
and symptoms of illness begin to decrease.
• However, during the decline period, patients may become susceptible to
developing secondary infections because their immune systems have
been weakened by the primary infection.

iv. Convalescent period

• The final period of disease is known as the convalescent period.
• During this stage, the patient generally returns to normal daily
functioning, although some diseases may inflict permanent damage that
the body cannot fully repair.

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Examples of microorganism that cause localized infections

Patterns of infections

• Localized infection: An infection that affects only one body part or

organ.

• Systemic infection: An infection which is affecting the entire body.

• Opportunistic infection:

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Examples of microorganism that cause systemic infections
• Chronic infection: An infection which persists for months e.g. hepatitis
and mononucleosis
• Latent infection: An infection that does not produce visible signs of a
disease, but may be transmitted to another host.
• Mixed infection (polymicrobial infection): An infection caused by
more than a single pathogen.
• Nosocomial infections (hospital acquired infections): Are infection(s)
acquired during the process of receiving health care that was not
present during the time of admission.
• Focal infection: An infection at a specific location that may spread to
another region of the body.
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6. Outcome
• Death, or recovery or persistent infection or sequelae.
• In recovery from an infection, the multiplication of the infectious agent is
brought under control.
• The microbe decreases in numbers and ceases to spread through the
body or cause progressive damage.
• In the process of recovery from an infectious disease, damaged tissues
are repaired and reconstituted.
• Sometimes the microorganism is completely destroyed and tissues
sterilised, or this fails to take place and the microorganism persists in
the body, in some instances continuing to cause minor pathological
changes.
• Sequelae: long-term or permanent damage to tissues or organs.
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Types of infections
• Self-limiting infections: Are infections that resolve spontaneously, with or
without specific treatment.
• Primary infection: The initial infection of a host by a pathogen.
• Secondary infection: An infection that occurs during or after treatment for
another infection.
• Acute infection: An infection is characterized by sudden or rapid onset of
disease, which can be resolved quickly by robust innate immune
responses exerted by the host or, instead, may kill the host.
• Reinfection: a recurrence caused by a different organism than was initially
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present. 50
5. Damage
• During infection process, some pathogens induce damage in the host.
• How do they damage host cells?
i. The direct local action of the pathogen. Examples:
• Virus infections result in a shutdown of RNA synthesis (transcription),
protein synthesis (translation) and DNA synthesis in the host cell.
• Colonisation of the tooth surface by Streptococcus mutans leads to
plaque formation, and the bacteria held in the plaque utilise dietary sugar
and produce acid. Locally produced acid decalcifies the tooth to give
caries.
ii. Pathogens release toxins which damage host cells.
iii. Indirect damage via inflammation.
iv. Indirect damage via immune response.
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7) Portals of Exit
• In addition to portals of entry, the spread of disease also depends on
portals of exit.
• Portals of entry in many cases are identical to the portals of entry.
• Pathogens often exit from the body of an infected host in secreted
materials, such as nasal secretions, saliva, sputum, and respiratory
droplets.
• Pathogens can also exit in the blood, vaginal secretions, semen, urine,
and faeces.
• Both portals of entry and portals of exit are important considerations for
health care providers, especially in controlling the spread of disease
within a patient population.
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Assignment (fill the table below)

Portal of exit Pathogens
Nasal secretions
Saliva
Sputum
Respiratory droplets
Blood
Vaginal secretions
Semen
Urine
Faeces
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Further Reading/Assignment
1. Mims, C., Nash, A., and Stephen, J. 2015. Mims Pathogenesis of
Infectious Disease, 6th ed. Academic Press, San Diego.
2. Chapter 5 and Chapter 16.
Smith, Molly and Selby, Sara, "Microbiology for Allied Health
Students" (2017). Biological Sciences Open Textbooks. 15.
https://oer.galileo.usg.edu/biology-textbooks/15

3. Assignment:
oRead Murray Medical Microbiology, Chapter 10.
oExplain how the immune responds to a (i) bacterial infection, (ii) viral
infection and (iii) fungal infection.
oExplain how bacteria, viruses and fungi evade the immune response. 59

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