S1 L1 - Intro to Infection

Question 1

Define infection

Disease is caused by…

WHO Priority Pathogens list

5 generic stages of how a microorganism (particually bacteria) could cause an infection within a human

Answer 1

# Define infection:
Invasion of a host’s body tissues by micro-organisms,
followed by multiplication of these agents and the subsequent reaction of these agents with the host’s defences

Disease is caused by…
Microbial multiplication, toxins, host response

WHO Priority Pathogens list:
WHO have a pathogen priority list - critical, high and medium urgencies of getting new antibiotics against these organisms

5 generic stages of how a microorganism (particually bacteria) could cause an infection within a human:
Exposure
Adherence
Invasion
Multiplication
Dissemination

Question 2

• *1. Exposure**
• Transmission is split into two broad categories, name and describe these
• One of the transmissions is split into a three sub-categories, name and describe these
• One of the sub-categories, is split into two, name both and describe
• Second of the sub-categories can be further split into two types

One other way of getting exposed

Answer 2

1. Exposure
Two broad categories:
- Vertical transmission/mother-child transmission: this is transmission of an infection from a mother to their foetus/baby during pregnancy or childbirth, e.g. HIV.
When does the transmission occur: during pregnancy across the placenta, during delivery if the micro-organism is swallowed by the child in the birth canal and, postnatally via the mother’s breast milk
- Horizontal transmission, encompasses any form of transmission which is not from parent to child. Further sub-categories: contact, inhalation and ingestion.

1. Contact- involves direct contact between the source and the host. This can be either direct or indirect.
   * *Direct** contact transmission occurs when there is physical contact between an infected and a susceptible person, e.g. STIs
   * *Indirect** contact transmission occurs when there is no direct human-to-human contact, but the susceptible patient comes in contact with a vector or a contaminated surface/ object (must be an act of making physical contact with an object that an infected person has contaminated e.g. a door handle or vector)
2. Inhalation - involves the entry of infective microorganisms through the respiratory tract. This can be broadly split into aerosol/airborne and droplet transmission.
   * *- Aerosol spread:** The particle which has been coughed, sneezed out and is extremely small and will hang in the air for some time.
   - Droplet spread: A much larger particle which when coughed or sneezed out will fly for a short distance before dropping to the floor or a surface which it may then contaminate.

3. Ingestion - involves the entry of infective organisms through the gastrointestinal system. It mainly consists of faeco-oral transmission e.g. drinking water contaminated with sewage, eating shellfish/raw fruit and vegetables that have been harvested or washed in contaminated water.

One other way of getting exposed:
Through patients microbiota (commensal) - microbiota = micro-organism carried on skin and mucosal surfaces, normally harmless or beneficial, by can be harmful if transferred to other sites

Question 3

• *2. Adherence**
• What is this?
• Specific example in bacteria of adherence
• *3. Invasion**
• Two types

Answer 3

2. Adherence:
What is this?
Adherence is the binding of a pathogen to a host cell. This is done using an adhesion protein, or ligand, on the bacterial cell wall or viral capsule surface, which then binds to a receptor (a carbohydrate structure bound to the lipid membrane) on a host cell.
Fimbriae are also believed to be involved in attaching some bacteria to a solid surface or another cell

3. Invasion:
Phagocytic cell invasion
Phagocytosis is a normal process for macrophages and is a process some bacteria can actually withstand and use to invade a macrophage (using virulence factors, such as strengthened cell walls and efflux pump systems) e.g. TB
Non-Phagocytic cell invasion
Bacteria that invades non-phagocytic cells work slightly differently by something called the zipper method. The bacterium will bind to a receptor that is involved in binding to other cells, which tricks the cell into forming a cell junction with it. The bacterium is relatively small compared to the host cell so the host cell tries to spread over the adhesive surface of the bacterium, endocytosing it (receptor-mediated endocytosis).

Question 4

• *4. Multiplication**
• name bacteria’s use

5. Dissemination

Answer 4

4. Multiplication
Multiplication of bacteria is via the mechanism of binary fission. The process starts with replication of the main strand of circular DNA of the bacteria into two copies. The next step is the replication of any plasmids; small circular strands of DNA which contain any ‘luxury genes’ ie those not crucial in the basic functioning of the bacteria. Multiple copies of these plasmids may be made. The final step is when the main strand copies move to opposite poles of the cell, the bacteria pinches in the middle and finally divides into two.
In viruses, the host cell’s multiplication machinery is taken over and used as a “factory” for further viruses to be produced based on the RNA/DNA of the initial virus which infected the cell. The copies are then released from the cell to infect further cells.

5. Dissemination
Dissemination involves the spreading of the bacteria/ viral load from one part of the body to another, e.g. TB - this is from the lungs to a secondary site (normally another organ) through the blood and lymphatics.

Question 5

• *Virulence and toxins**
• What are these?
• What are virulence factors?
• Examples of virulence factors
• How are toxins divided into?

Answer 5

- What are these?
Virulence is the ability of a micro-organism to infect a host (at all steps of the process)
- What are virulence factors?
Virulence factors are what helps the micro-organisms infect a host (at all steps in the process)
- Examples of virulence factors
Toxins, haemolysins, proteases…
- How are toxins divided into?
Endotoxins: Conists of lipopolysaccharide part of the cell wall of gram negative bacteria. Endotoxins cause an inflammatory response. Endotoxins do not produce an acquired immune response as they are not immunogenic.
Exotoxins: Toxins secreted by bacteria, that can destroy body cells and affect normal cellular metabolism

Question 6

• *Disease deteminants:**
• Pathogen
• Patient
• *How do we know a patient has an infection (and which infection)?**
• 3 methods

Answer 6

• *Pathogen:**
• Virulence factors
• Inoculum size
• Antimicrobial resistance
• *Patient:
• **Site of infection
• Co-morbidities
• *How do we know a patient has an infection (and which infection)?**
• History
• Examination
• Investigations

Question 7

• *1. History**
• What type of questions do you us if you suspect an infectious disease?

2. Examination

Answer 7

• *Infection History:**
• Potential exposures a patient may have had which includes: travel history for the last 6-12 mnths, the calendar time (eg Norovius as the winter vomiting bug), contact with any animals
• Relative time from exposure to presentation to indicate incubation time of the infection
• Vaccination history (don’t forget some people opt not to have their children vaccinated so it is important not to make assumptions)
• Symptoms of the presenting complaint (severity, duration, rash, radiation, muscular problems, numbness, vomiting, appetite etc)
• It is then important to explore patient symptoms further. One useful mnemonic for identifying more information about a particular symptom is SQITARS.

Site of symptom/pain:

• *Q**uality - how would they describe it? For example, a pain could could stabbing, or crushing
• *I**ntensity of the symptom
• *T**ime since onset
• *A**ggravating factors
• *R**elieving factors
• *S**econdary features/other symptoms
• *Examination:**
• Look at anything relevant in the patient history e.g. rashes, muscle stiffness
  e. g. Herpes zoster virus causes shingles that presents with a rash (limited to 1 or more dermatomes on the body)
  e. g. Neisseria Meningitidis is a non-blanching petechial rash (does not disappear when a tumbler/clear glass is rolled over it)

Question 8

• *3. Investigations**
• Supportive investigations examples
• Specific investigations examples for bacteria and virus

Answer 8

• *Supportive investigations:**
• Full blood count
• CRP (C-reactive protein, a sign of inflammation produced by the liver)
• U and E’s (urea and electrolytes - a sign of multiple issues, including kidney damage/failure)
• LFTs (liver function tests - sign of liver damage)
• Imaging (x-ray, ultrasound, MRI)
• Blood cultures (to grow bacteria)

Specific investigations:
Bacteriology:
• Specimen types: swabs, fluids, tissues
• “M,C&S”:
- microscopy: bacterial cells (e.g.Gram stain), patient cells e.g. cerebrospinal fluid (CSF)
- culture (grow the organism on an agar plate, incubate, see if anything grows - may have a specific look about it)
- antibiotic susceptibility (to see what microbial will kill them)
• Antigen detection
• Nucleic acid detection

Virology:
• antigen detection (the virus)
• antibody detection (the patient’s response)
• detecting viral nucleic acid (DNA or RNA)