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Infectious diseases

Infectious diseases are any disease caused by the presence of pathogens in the body.

Pathogens are agents that can disrupt homeostasis in the body. They can be bacteria,
viruses, protozoans, fungi, and other parasites.

The main sources of pathogens include soil, contaminated water, and infected
animals or people.

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Human Microbiome

Not all microorganisms are pathogenic.

The human microbiome is the collection of all the microorganisms living in

association with the human body. These include a variety of microorganisms like
bacteria, eukaryotes, and viruses.

The average human body has ten times more bacteria than human cells. However,
because bacteria are small (microorganisms), they only make up about 1-3% of a
human body’s mass.

The microorganisms that comprise the human microbiome are generally not harmful
to humans. They are actually essential for maintaining health. For example, some
microbes produce vitamins that human do not have the capacity to make. Some
microorganisms break down human food to exact nutrients essential for survival.
Other microorganisms teach the immune systems how to recognize dangerous
invaders.

Studies have demonstrated that changes in the composition of the human

microbiome correlate with numerous disease states, indicating the potential of using
these microbial communities to treat diseases.

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https://www.hmpdacc.org/overview/

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Digestive system microbiome

The digestive system is a host for various microorganisms with the following
functions:

1. Prevent the growth of pathogens

2. Stimulate the immune system to produce antibodies that can cross-react with
invading pathogens

3. Aid in the digestion of cellulose in ruminants

4. Produce essential nutrients

The figure on the right show some microbes found in different parts of the digestive
system.

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Koch’s Postulates

Koch’s postulates are four criteria that were established by Robert Koch (1884) to
establish a causative relationship between a microbe and a disease i.e. identify the
causative agent of a particular disease. These are:

1. The same pathogen must be present in every case of the disease.

2. The pathogen must be isolated from the diseased host and grown in pure culture

3. The pathogen from the pure culture must cause the disease when introduced into
a healthy but susceptible organism

4. The pathogen must be isolated from the inoculated animal and be shown to be
the original organism.

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Koch’s Postulates

The figure shows a representation of Koch’s postulates. Again, these are

1. The same pathogen must be present in every case of the disease.

2. The pathogen must be isolated from the diseased host and grown in pure culture

3. The pathogen from the pure culture must cause the disease when introduced into
a healthy but susceptible organism

4. The pathogen must be isolated from the inoculated animal and be shown to be
the original organism.

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Koch’s Postulates Modifications

There are some modifications in Koch’s postulates which include:

1. Some infectious agents cannot be cultured. Not all pathogens can be cultured in
the laboratory. For example, prions are misfolded proteins that cause diseases like
mad-cow disease, scrapie (in sheep), and creutzfeldt-jakob disease. Prions cannot
be cultured and so will not fulfill one requirement in Koch’s postulates.

2. Some pathogens have non-virulent strains. Virulence is described as an ability of

an organism to infect the host and cause a disease. Some pathogens have
versions that do not have this ability. They are the same species of microorganism
but have small difference in the way they colonize a host cell. The presence of this
non-virulent strain in a person although fulfills Koch’s postulates will not link them
to a disease.

An example of a non-virulent strain is the non-encapsulated Diplococcus pneumoniae.

The capsule is necessary for virulence because it protects the bacteria from being
digested by enzymes in the host cell. The capsule also helps the bacteria colonize the
nasopharyngeal area of the host where it multiplies. The absence of the capsule
therefore makes a strain non-virulent.

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Types of Pathogens: Bacteria

Pathogens can be classified according to the type of organisms that causes the
disease.

Bacteria one type of pathogen.

Bacteria are prokaryotes. They can spread through water, air, soil, and through
physical contact.

There are two types of bacteria based on their cell wall.

1. Gram positive bacteria.

These bacteria have a thick cell wall. They retain a distinctive purple color when
stained with Gram Stain. The dye is retained in the cell because of their thick cell wall.

Some Gram-positive bacteria cause disease. Others normally occupy a particular site
in the body, such as the skin.

Examples of Gram positive pathogens include:

• Bacillus antrhacis – the causative agent of anthrax
• Corynebacterium diphtheria – the causative agent of diphtheria

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• Streptococcus pneumoniae – these commonly cause pneumonia, meningitis,
sinusitis, and middle ear infection
• Staphylococcus aureus – these often cause skin infections but can cause
pneumonia, heart valve infections, and bone infections

2. Gram negative bacteria

Gram-negative bacteria have a thinner cell wall compared to gram positive bacteria.
They are color red/pink after Gram-staining because the dye escapes from the cell.

Gram negative bacteria are among the most significant public health problems in the
world due to the high resistance to antibiotics. These microorganisms have great
clinical importance in hospitals because they put patients in the intensive care unit
(ICU) at high risk and lead to high morbidity and mortality.

Examples:
• Enterobacteriaceae - a large family of different types of bacteria that commonly
cause infections in healthcare settings.
• Klebsiella pneumoniae - These can cause different types of healthcare-associated
infections, including pneumonia, bloodstream infections, wound or surgical site
infections, and meningitis. Klebsiella have developed resistance to some
antibiotics. They commonly infect sick patients receiving treatment for other
conditions. Patients who are at risk of infection are those who require devices like
ventilators, iv catheters and those taking long courses of certain antibiotics. In
general, healthy people do not get Klebsiella infections.
• Helicobacter pylori - can live in the digestive tract and after many years can cause
ulcers. For some people, infection with H. pylori can lead to stomach cancer.

https://www.ncbi.nlm.nih.gov/books/NBK538213/

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Types of Pathogens: Parasites

Parasites are organisms that live on or in a host organism. They get their food from or
at the expense of its host.

There are three main classes of parasites that can cause disease in humans: protozoa,
helminths, and ectoparasites.

1. Protozoa

Protozoa are microscopic, one-celled eukaryotic organisms. They can be free-living or

parasitic in nature. Protozoa can multiply in humans.

Human to human transmission of protozoa that live in human intestine generally

occurs through a fecal-oral route (contaminated food or water, or person-to-person).
Transmission of protozoa that live in the blood or tissues of humans occur through
arthropod vectors like a bite of a mosquito.

Example:
Plasmodium – the causative agent of malaria. There are four kinds of malaria
parasites infect humans: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae.
People usually get malaria by being bitten by an infective female Anopheles

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mosquito. Only Anopheles mosquitoes can transmit malaria. These mosquitoes must
have been infected through a previous blood meal taken from an infected person.
When a mosquito bites an infected person, a small amount of blood is taken in which
contains Plasmodium. About 1 week later, when the mosquito takes its next blood
meal, the Plasmodium mix with the mosquito’s saliva and are injected into the person
being bitten.

2. Helminths

Helminths are large, multicellular organisms that are generally visible to the naked
eye in their adult stages. Like protozoa, helminths can be either free-living or parasitic
in nature. In their adult form, helminths cannot multiply in humans. There are three
main groups of helminths that are human parasites:

Flatworms (platyhelminths) – these include the trematodes (flukes) and cestodes

(tapeworms) Ex. Taenia
Thorny-headed worms (acanthocephalins) – the adult forms of these worms reside
in the gastrointestinal tract.
Roundworms (nematodes) – the adult forms of these worms can reside in the
gastrointestinal tract, blood, lymphatic system or subcutaneous tissues. Alternatively,
the immature (larval) states can cause disease through their infection of various body
tissues. Ex. Ascaris

3. Ectoparasites

Ectoparasites generally refer to organisms such as ticks, fleas, lice, and mites that
attach or burrow into the skin and remain there for relatively long periods of time
(e.g., weeks to months).

https://www.cdc.gov/parasites/about.html

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Types of Pathogens: Viruses

A virus is a set of genes, composed of either DNA or RNA, packaged in a protein-

containing coat (capsid). Some viruses also have an outer lipid membrane external to
the coat called an envelope.

Viruses have an requires a host cell for growth and replication. Viruses do not have a
nucleus, cytoplasm, mitochondria, or other cell organelles.

Pathogenic viruses are viruses that can infect and replicate within human cells and
cause diseases.

https://www.sciencedirect.com/science/article/abs/pii/S1567134820300472#:~:text
=Pathogenic%20viruses%20are%20viruses%20that,major%20threat%20to%20public
%20health.

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Pathogen Reservoirs
Reservoirs are where pathogens normally reside that allow them to persist over long
periods of time.

Reservoirs can be nonliving sites or living organisms.

Nonliving reservoirs can include soil and water in the environment. These may
naturally harbor the organism because it grows in that environment. These
environments may also become contaminated with pathogens from other sources
like human feces or intermediate hosts.

A human acting as a reservoir of a pathogen may or may not be capable of

transmitting the pathogen, depending on the stage of infection and the pathogen.

https://courses.lumenlearning.com/microbiology/chapter/modes-of-disease-
transmission/

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Carriers
A carrier is an individual capable of transmitting a pathogen without displaying
symptoms.

A passive carrier is contaminated with the pathogen and can mechanically transmit it
to another host. A passive carrier is not infected.
For example, a health-care professional who fails to wash his hands after seeing a
patient harboring an infectious agent could become a passive carrier, transmitting the
pathogen to another patient who becomes infected.

An active carrier is an infected individual who can transmit the disease to others. An
active carrier may or may not exhibit signs or symptoms of infection.
For example, active carriers may transmit the disease during the incubation period
(before they show signs and symptoms) or the period of convalescence (after
symptoms have subsided).

Active carriers who do not present signs or symptoms of disease despite infection are
called asymptomatic carriers.

Examples of pathogens transmitted by asymptomatic carriers: hepatitis B virus,

herpes simplex virus, HIV, and nCOV2.

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https://courses.lumenlearning.com/microbiology/chapter/modes-of-disease-
transmission/

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Transmission

Transmission must occur for an infection to spread, regardless of the reservoir.

Transmission from the reservoir to the individual must occur first. Then, the individual
must transmit the infectious agent to other susceptible individuals (directly or
indirectly).

These are 3 transmission mechanisms:

1. Contact Transmission
Contact transmission includes direct contact or indirect contact. Person-to-person
transmission is a form of direct contact transmission. The pathogen is transmitted by
physical contact between two individuals through actions such as touching, kissing,
sexual intercourse, or droplet sprays.

2. Indirect contact transmission

This involves inanimate objects called fomites that become contaminated by
pathogens from an infected individual or reservoir. For example, an individual with
the common cold may sneeze, causing droplets to land on a fomite such as a
tablecloth, or the individual may wipe her nose and then transfer mucus to a fomite
such as a doorknob or towel. Transmission occurs indirectly when a new susceptible

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host later touches the fomite and transfers the contaminated material to a
susceptible portal of entry. Fomites can also include objects used in clinical settings
that are not properly sterilized, such as syringes, needles, catheters, and surgical
equipment.

3. Vehicle transmission
This refers to transmission of pathogens through vehicles such as water, food, and air.
For example, water contamination through poor sanitation methods leads to
waterborne transmission of disease.

4. Vector transmission
A vector is a mode of disease transmission from one host to another through
mechanical of biological means.

Mechanical transmission is facilitated by a mechanical vector, an animal that carries a

pathogen from one host to another without being infected itself.

For example, a fly may land on fecal matter and later transmit bacteria from the feces
to food that it lands on. A human eating the food may then become infected by the
bacteria, resulting in a case of diarrhea or dysentery.

Biological transmission occurs when the pathogen reproduces within a biological

vector that transmits the pathogen from one host to another.

Arthropods are the main vectors responsible for biological transmission. Most
arthropod vectors transmit the pathogen by biting the host, creating a wound that
serves as a portal of entry. The pathogen may go through part of its reproductive
cycle in the gut or salivary glands of the arthropod to facilitate its transmission
through the bite.

Examples:
• hemipterans (called “kissing bugs” or “assassin bugs”) transmit Chagas disease to
humans by defecating when they bite, after which the human scratches or rubs the
infected feces into a mucous membrane or break in the skin.
• Mosquitoes - transmit malaria and other diseases
• Lice - transmit typhus

https://courses.lumenlearning.com/microbiology/chapter/modes-of-disease-
transmission/

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Pathogenesis is literally how disease (pathos) begins (genesis) or develops. It refers to
the chain of events leading to that disease.

Pathogenesis occurs as a consequence of complex interactions between an infecting

pathogen and the host system.

The right panel describes a general sequence of events for disease progression after
infection.

The left panel shows the pathogenesis of rabies caused by the rabies virus Rabies
lyssavirus.

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Pathogenicity refers to the potential capacity of certain species of microbes to
cause a disease (ability to cause disease).

Virulence is the degree of pathogenicity within a group or species of parasites as

indicated by case fatality rates and/or the ability of the organism to invade the tissues
of the host.

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Virulence factors are molecules expressed and secreted by pathogens (bacteria,
viruses, fungi and protozoa) that give them the ability to cause disease.

The pathogenicity of an organism is determined by its virulence factors.

Virulence factors allow pathogens to

1. colonize of a niche in the host (this includes adhesion to cells)

2. Immunoevasion - evade the host's immune response

3. Immunosuppression - inhibit the host's immune response

4. Obtain nutrients from the host

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The following are examples of virulence factors:

1. Pilus. This is part of a bacteria that allows them to adhere and colonize
environmental surfaces or cells. These make them resistant to flushing.

2. Capsules. These are protective coatings that surround the entire bacterial cell wall.
They protect the bacteria from host defenses such as phagocytes (cells that protect
the body by ingesting harmful foreign particle).

3. Exotoxins. These are types of proteins secreted from pathogenic bacteria (both
gram positive and gram negative). And example is neurotoxin.

4. Endotoxins. These are part of the outer membrane of Gram-negative bacteria.

They can cause fever, changes in blood pressure, inflammation, lethal shock, and
many other toxic events.

5. Proteases. These are enzymes that break down proteins. Proteases that act as
virulence factors generally target proteins of the immune system such as antibodies.

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Virulence factors

The diagram shows several examples of virulence factors in a bacteria.

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Using the concepts discussed, the following slides will describe HIV infection.

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HIV/AIDS

Human immunodeficiency virus is a virus that attacks cells that help the body fight
infection (CD4+ T-cells), making a person more vulnerable to other infections and
diseases. If left untreated, HIV can lead to the disease AIDS (acquired
immunodeficiency syndrome).

The genomic material of HIV is an RNA molecule.

AIDS is the late stage of HIV infection that occurs when the body’s immune system is
badly damaged because of the virus.

https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids
https://www.cdc.gov/hiv/basics/whatishiv.html

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HIV Life Cycle

1. Binding and Fusion

HIV binds specifically to its host cell (CD4+ T-cell) through specific interaction of
proteins found on the surface of the virus and the host cell. The CD4+ host cell is
important in the human immune response. HIV destroys the body’s CD4+ T-cells and
compromises the body’s immune system.

2. Entry
HIV enters the cell and releases its genetic material, an RNA molecule.

3. Reverse transcription
The RNA becomes a template to synthesize DNA in a process called reverse
transcription (RNA to DNA – recall the central dogma). This is necessary for the
genetic information to be integrated into the host cell. An RNA molecule cannot
integrate with the chromosomal DNA but a DNA molecule can.

4. Integration
After reverse transcription, the viral DNA is integrated into the chromosomal DNA of
the host cell.

5. Viral RNA and protein expression

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Viral DNA that has been integrated into the host chromosomal DNA becomes a
template for viral RNA transcription and viral protein translation. These are needed to
assemble new viral particles.

6. Assembly and budding

HIV is assembled using the HIV RNA (genetic material) and HIV proteins made by the
host cell. This will form buds in the host cell forming an immature virus.

7. Maturation
HIV that has budded out of the host cells matures and is ready to infect other host
cells.

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HIV vector
HIV is a blood borne pathogen like Hepatitis B and C viruses and the Plasmodium
parasite that causes malaria. However, HIV has no vector. It cannot be transmitted by
blood-feeding arthropods.

HIV transmission
HIV is transmitted through specific activities. Most commonly, people get or transmit
HIV through sexual behaviors and needle or syringe use.

Only certain body fluids—blood, semen (cum), pre-seminal fluid (pre-cum), rectal
fluids, vaginal fluids, and breast milk—from a person who has HIV can transmit HIV.
These fluids must come in contact with a mucous membrane or damaged tissue or be
directly injected into the bloodstream (from a needle or syringe) for transmission to
occur. Mucous membranes are found inside the rectum, vagina, penis, and mouth.

HIV incubation period

The period from infection to the primary seroconversion illness is usually 1 to 4

weeks, which varies widely between patients.

Seroconversion is the transition from the point of viral infection to when antibodies
become present in the blood.

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Antibodies are proteins produced by the immune system that specifically bind to and
target the virus.

Epidemiology (Global statistics)

• 38.0 million people globally were living with HIV in 2019.
• 1.7 million people worldwide became newly infected with HIV in 2019.
• 690 000 people died from AIDS-related illnesses in 2019.
• 75.7 million people have become infected with HIV since the start of the epidemic.
• 32.7 million people have died from AIDS-related illnesses since the start of the
epidemic.

https://www.unaids.org/en/resources/fact-sheet

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The figure lists the different ways to diagnose HIV infection.

1. ELISA or enzyme-linked immunosorbent assay detects the presence of antibodies

or antigens specific to the virus in the patient specimen (blood, oral sample)

2. Western blot is similar to ELISA. It detects the presence of antibodies or antigens

specific to the virus in the patient specimen using a different format. This method
is rarely used now.

3. qPCR or quantitative polymerase chain reaction is a method that specifically

detects the presence of the HIV genetic material in the patient specimen.

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Enzyme-linked immunosorbent assay (ELISA) is a test that detects antibodies the
body produced against HIV or HIV-specific antigens in the blood.

Antibodies are proteins produced by the immune system, which helps your body
fight disease. The immune system produces the antibodies in response to the
presence of foreign substances, such as viruses.

Antigens are any foreign substance in the body that causes the immune system to
respond.

If a person has HIV, an antigen called p24 is produced even before antibodies
develop. An antigen/antibody test performed by a laboratory on blood from a vein
can usually detect HIV infection 18 to 45 days after an exposure.

To detect antibodies against HIV (left panel). Purified HIV-specific proteins (produced
in the lab) are immobilized on a surface and used as “bait” for HIV antibodies in the
human blood sample. If a person is infected with HIV, the body will produce
antibodies against it. These antibodies will bind to the “HIV protein bait” in the test.
To visualize the binding of the HIV antibodies, proteins labeled with chromophore or
fluorophore that bind specifically to the HIV antibodies are used.

To detect HIV-specific proteins/antigens (right panel). HIV-specific antibodies

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produced in the lab are immobilized on a surface and used as “bait” for HIV-specific
proteins (antigens). A person infected with HIV will have proteins specific to the virus.
These will be present in their blood and bind to the immobilized HIV-specific
antibodies (bait). To visualize the binding, antibodies specific HIV-antigen and labeled
with chromophore or fluorophore are used.

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HIV Diagnosis: qPCR (quantitative PCR):

This method quantitatively detects the presence or absence of HIV’s genetic material
(RNA) in the blood. This can detect very early infections of the virus, even before the
body has produced antibodies against the virus. This test may be performed just days
or weeks after exposure to HIV. This is the most accurate type of test for diagnosing
HIV. However, this is not used as often because this is more expensive, labor- and
time-intensive.

This method works similar to PCR. The template is the HIV RNA genetic material. If it
is present in the blood sample, amplification will occur. If HIV genetic material is
absent, nothing will be amplified (no template). The primers used are specific to
sequences in the HIV genetic material.

Before doing PCR, the HIV RNA needs to be converted to DNA in a process called
reverse transcription or complementary DNA (cDNA) synthesis. It is the resulting
cDNA that will be run in the PCR.

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HIV Treatment

The treatment for HIV is called antiretroviral therapy (ART). ART involves taking a
combination of HIV medicines (called an HIV treatment regimen) every day. ART is
recommended for everyone who has HIV. ART can’t cure HIV, but HIV medicines help
people with HIV live longer, healthier lives. ART also reduces the risk of HIV
transmission.

HIV attacks and destroys the infection-fighting CD4 cells of the immune system. Loss
of CD4 cells makes it hard for the body to fight off infections and certain HIV-related
cancers.

HIV medicines prevent HIV from multiplying (making copies of itself), which reduces
the amount of HIV in the body (called the viral load). Having less HIV in the body
gives the immune system a chance to recover and produce more CD4 cells. Even
though there is still some HIV in the body, the immune system is strong enough to
fight off infections and certain HIV-related cancers.

By reducing the amount of HIV in the body, HIV medicines also reduce the risk of HIV
transmission. A main goal of HIV treatment is to reduce a person’s viral load to an
undetectable level. An undetectable viral load means that the level of HIV in the
blood is too low to be detected by a viral load test. People with HIV who maintain an

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undetectable viral load have effectively no risk of transmitting HIV to their HIV-
negative partners through sex.

https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/21/51/hiv-treatment--
the-basics

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