S1) What is an Infection? Flashcards

1
Q

What is an infection?

A

Important elements to infection:

  • Invasion of a host’s tissues by micro-organisms
  • Disease caused by:
  • Microbial multiplication
  • Toxin production by some pathogens
  • Host response to the microbial infection
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2
Q

In this context, when we say ‘host’ what do we mean?

A

Human beings

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3
Q

Describe how the host response can cause disease

A

In many diseases, what causes the signs and symptoms of the disease are the inflammatory processes produced by the host in response to invasion

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4
Q

Describe how infection can arise from the patient’s own micro-organisms

A
  • micro-organisms (like bacteria or fungi) are naturally carried on skin and mucosal surfaces
  • normally harmless or even beneficial
  • transfer to other sites can be harmful (so if they move from the skin and invade tissues)
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5
Q

What does the word ‘commensals’ mean?

A

The vast range of different micro - organisms that are naturally and normally carried on skin and mucosal surfaces

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6
Q

What is sometimes the issue with the word ‘commensals’?

A

It often implies that the micro-organisms found naturally and normal on the skin and mucosal surfaces cannot cause disease, but that is not the case

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7
Q

What can be used instead of the word ‘commensals’? (better word)

A

Microbiota

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8
Q

What is meant by the term ‘microbiota’?

A
  • covers all the microbial organisms in a particular environment (in this case on skin or mucosal surfaces)
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9
Q

Apart from infections arising from the patient’s own organisms, how else do people get infections from ‘patient’?

A
  • People can get infected from other people, either through direct contact or through some sort of intermediary
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10
Q

Describe the 3 ways that infection can be spread from person to person

A
  • (very close) Physical contact required for some infections, e.g. sexually transmitted infections (gonorrhea, chlamydia, HIV, potentially Hep B)
  • Airborne spread may be sufficient for other infections (e.g. chickenpox, influenza, TB, Covid-19)
  • (Intermediary may be a) Vector may be necessary (e.g. mosquito for malaria, yellow fever)
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11
Q

Briefly state the 4 main ways that people can get infections from the environment

A
  • Water
  • Food
  • Air
  • Surfaces
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12
Q

Give an example of how food and water as environmental factors can cause infection

A

-Transmission due to ingestion of contaminated food (e.g. food poisoning) or water (e.g. contaminated shower heads and someone getting showered with water and contaminated droplets, which can be inhaled to infect the person)

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13
Q

Give an example of how food and water as environmental factors can cause infection

A

-Transmission due to ingestion of contaminated food (e.g. food poisoning) or water (e.g. contaminated shower heads and someone getting showered with water and contaminated droplets, which can be inhaled to infect the person)

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14
Q

Describe how air as an environmental factor can cause infection

A
  • Inhalation of air contaminated by environmental organisms
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15
Q

Describe how surfaces as an environmental factor can cause infection

A
  • Contact with contaminated surfaces, including medical devices/surgical instruments that haven’t been decontaminated properly, following use on a prior patient can lead to hundreds of infected patients
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16
Q

What are the 2 classes for modes of transmission?

A
  • Horizontal transmission
  • Vertical transmission
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17
Q

What is horizontal transmission?

A

Transmission by direct contact between infected and susceptible individuals or between disease vectors and susceptible individual

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18
Q

What is vertical transmission?

A

generational transmission of viruses from parents to their offspring

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19
Q

Name and give examples of modes of horizontal transmission

A

-Contact:

  • direct - STD’s
  • indirect - person to person spread
  • vectors - e.g. mosquitos
  • Inhalation:
  • droplets
  • aerosols
  • Ingestion (primarily faecal-oral transmission/eating someone else’s something else’s poo)
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20
Q

In the vein of inhalation, compare and contrast droplets and aerosols

A

Droplets:

  • Large particles, often above 5 micrometres in diameter
  • May be coughed out
  • May travel for a metre or 2, and then drop

Aerosols:

  • Small particles, less than 5 micrometers in diameter
  • Remain suspended in air currents for a long time, and drifts as air currents move them
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21
Q

What is the main difference between droplets and aerosols?

A

Droplet transmission = short range

Aerosol transmission = much longer in range

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22
Q

Describe the mode of vertical transmission

A

Mother to child before or at birth:

  • e.g., HIV-1 can be acquired in the uterus (via breaks in the placental barrier or transcytosis of cell-associated virus), during delivery (intrapartum), or via breastfeeding.
  • Bacteria from the mother’s vagina, may enter the amniotic fluid surrounding baby and cause infection even before it’s born - can result in meningitis or sepsis
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23
Q

What happens when the micro-organism moves into the host?

A

It causes symptoms following a series of steps

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24
Q

Name the steps that occur before microorganisms cause symptoms in the host

A
  1. Exposure
  2. Adherence
  3. Invasion
  4. Multiplication
  5. Dissemination
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25
Q

Describe the exposure step of how microorganisms cause disease

A
  • Exposure of the victim/host to microorganism
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26
Q

Describe the adherence step of how microorganisms cause disease

A

Microorganism adheres to some kind of cell surface (whether that is on the mucosal membrane or if it has already entered the body onto cell surfaces e.g. blood vessels)

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27
Q

Describe the invasion step of how microorganisms cause disease

A
  • Either intracellular, as with all viruses that have to invade cells in order to replicate
  • Or invasion into tissues and spread between cells in the intracellular matrix
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28
Q

Describe the multiplication step of how microorganisms cause disease

A
  • Division of bacteria
  • or multiplication of bacteria within the host cell
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29
Q

Describe the dissemination step of how microorganisms cause disease

A
  • Could be local dissemination going into the blood stream or else where
  • Or spread out into the general environment to other potential patients/contacts
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30
Q

What do the micro-organisms employ to cause the disease symptoms in the host?

A

Virulence factors

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31
Q

What are virulence factors?

A
  • chemicals which can enhance the survival of microorganisms and their reproduction within the host
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32
Q

What are the 2 categories of virulence factors?

A
  • Exotoxins
  • Endotoxins
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33
Q

Name some exotoxins (virulence factors)

A
  • Cytolytic
  • AB toxins
  • Superantigens
  • Enzymes
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34
Q

Describe the mechanism of cytolytic exotoxins

A
  • membrane damaging
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35
Q

Describe the mechanism of AB Toxins

A
  • Two part toxins where B binds to the cell and delivers
  • A to the cytosol which is often an enzyme that interferes with cell function
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36
Q

Describe the mechanism of superantigens

A
  • Microbial proteins that bind both class II MHC molecules and T-cell receptors (causing activation of the T cell)
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37
Q

Describe the mechanism of enzymes (in the vein of virulence factors)

A
  • Destroy tissue into which bacteria is trying to invade
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38
Q

What are endotoxins?

A
  • Cell wall components in particular lipopolysaccharide-protein complexes
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39
Q

Describe how virulence factors ultimately lead to symptoms and signs of disease

A
  • Virulence factors cause host cell damage either directly to as a result of tether immune response to the virulence factor
  • As a consequence of this, we end up with the symptoms and signs of disease e.g. cytokine storms/SEPSIS.
40
Q

What are the two classes of disease determinants?

A
  1. Pathogen
  2. Patient
41
Q

Describe the ‘pathogen’ disease determinants

A
  • Pathogen’s Virulence factors - things the M/O does or doesn’t produce e.g. some stains of bacteria produce toxins, which make the disease worse
  • Inoculum size - the amount of microorganism that causes the infection
  • (antimicrobial resistance) technically not a disease determinant, however resistant bacteria would mean the infective period would carry on for longer until an effective antibiotic is finally used (but might be too late)
42
Q

Describe the ‘patient’ disease determinants

A
  • Site of infection in the patient (e.g. infection in the heart is more severe than infection on skin with the same bacteria)
  • Presence or absence of co-morbidities e.g. The other illnesses that a patient may have, e.g. asthma, diabetes, cancer HIV come with increased severity of infection, due to immunosuppression in transplant or cancer patients that have had immune system depleted by chemotherapy, for example)
43
Q

What questions are there to answer if a patient presents with an infection?

A
  • Is there an infection?
  • Where is the infection?
  • What is the cause of the infection?
  • What is the best treatment?
44
Q

What is the 3-step process of investigating the patient’s infection?

A
  1. History
  2. Examination
  3. Investigation
45
Q

Describe the history step of investigating a patient’s infection

A
  • Asking the patient about what has been wrong with them:

Split into:

  1. Symptoms:
    - focal (specific part of body) , systemic (can’t be pinned down to a specific site, e.g. fever and weakness)
    - Severity
    - Duration (when they started and how long it has been going on for)
  2. Potential exposures (been in contact with anyone else with a similar sort of infection/ recent travel/contact with animals)
46
Q

Describe the examination step of investigating a patient’s infection

A
  • Organ dysfunctions - evidence of any organs not working well
47
Q

Describe the investigation step of investigating a patient’s infection

A
  • Specific investigations - to try and identify the specific causative organism causing a potential infection
  • Supportive investigations - just confirm that the patient is suffering from infection but don’t actually give a name to the micro-organism but give a general clue of what is going on. They are NOT diagnostic
48
Q

Name 5 supportive investigations

A
  • Full blood count – take a sample of blood from patient’s vein and look at numbers of white cells - neutrophils, lymphocytes
  • C-reactive protein (CRP) test
  • blood chemistry tests – liver and kidney function tests
  • imaging – x-ray, ultrasound, magnetic resonance imaging (MRI)
  • histopathology
49
Q

Describe the use of full blood count in supportive investigations

A

Monitoring the numbers of white cells (lymphocytes and neutrophils) is important as:

  • Neutrophils raises in bacterial infection
  • Lymphocytes raises in viral infections
  • Note that you can also get increased neutrophil and lymphocyte count in other non-infective processes too, which is why it is in no way diagnostic
50
Q

Describe what happens in a C-reactive protein (CRP) test

A
  • A chemical, known as an acute phase protein just tells you that there is an inflammatory process going on
  • Someone with a serious infection will have a raised CRP
51
Q

Describe the use of blood chemistry tests

A
  • E.g useful in suggesting that a patient has hepatitis (inflammation of the liver)
  • useful in suggesting some impact on kidney function
  • Also useful in the vein of infection management
52
Q

Describe how blood chemistry - liver and kidney function tests can be useful for management of infections

A
  • Many antimicrobial drugs that we use to treat infections are either metabolised by the liver, or excreted by the kidney.
  • Thus, (following these tests), if there is evidence of liver or kidney disease that may affect metabolism or excretion, it may be necessary to adjust the dose of an antimicrobial to avoid poisoning the patient by inadvertently giving them an overdose of the antimicrobial
53
Q

Describe how imaging – x-ray, ultrasound, magnetic resonance imaging (MRI) can be useful in supportive investigations

A
  • E.g chest x-ray can provide good evidence of pneumonia
  • Ultrasound of abdomen might show an abscess within the abdomen
  • MRI may show inflammation of the bone, supporting diagnosis of osteomyelitis - infection of the bone
54
Q

Describe the use of histopathology in supportive investigations

A

Involves staining pieces of tissue and looking at them under a microscope

May show:

  • Collections of cellular infection
  • Collections of bacteria and neutrophils (pus) linked to bacterial infection
  • Good at demonstrating fungal infections (the spread of mould through tissues)
55
Q

What are the 2 classes of specific investigations?

A
  • Bacteriology
  • Virology
56
Q

In general, what happens in bacteriology?

A

We try to grow the bacteria causing the disease

57
Q

Name the aspects of bacteriology

A
  • Specimen collection
  • M,C&S (Microscopy, culture, antibiotic susceptibility)
  • Antigen detection
  • Nucleic acid detection
58
Q

Describe the specimen types of bacteriology

A
  • swabs (e.g. of pus - basically a Q tip that has been dipped into bases fluid)
  • fluids (e.g. urine sample if suspected to have a UTI
  • tissues (e.g. heart valve taken out during surgery of patients suspected to have infection of heart valve)
59
Q

What is CSF and what is it’s importance in bacteriology?

A
  • Cerebrospinal fluid
  • Th fluid surrounding brain and spinal chord
  • In cases of meningitis, there is an increase in the number of white cells in the CFS
  • We can look at CFS under a microscope, on a slide to support or discount the possibility of an infection like meningitis
60
Q

Describe the microscopy part of M,C&S (Microscopy, culture, antibiotic susceptibility) of bacteriology

A
  1. Microscopy - looking at the specimen under the microscope:
  • Bacterial cells - we might carry out a gram stain (a special stain that divides bacteria into gram positive and gram negative
  • Patient cells, where we look directly at the specimen e.g. cerebrospinal fluid (CSF)
61
Q

Describe the culture part of M,C&S (Microscopy, culture, antibiotic susceptibility) of bacteriology

A
  1. Culture - when we try to grow the organism by putting some of the sample on an agar plate.

Put sample into agar plate and incubate for at least 18 hours.

Look at plate the next day and see if anything growing on it.

If there are any pathological bacteria growing on it, if they look significant, we will try and identify them (if the specimen was a heart valve, anything that would grow from that heart valve would likely be significant and warrant further investigation

62
Q

What is agar?

A

A polysaccharide jelly derived from a seaweeds

63
Q

What is the most common agar we use?

A
  • Blood agar
  • This is the seaweed jelly to which sheep or horse RBC’s have been added
  • RBC’s provide a nutrient source for the bacteria
64
Q

What term do we use to describe the agar medium, and why?

A

An ‘enriched’ medium as the plate with the protein and blood provides nutrients for a number of common bacteria.

65
Q

What do agar plates commonly contain?

A

Additional ingredients to facilitate bacterial growth, including proteins and sodium chloride

66
Q

Describe how other bacteria respond to blood

A
  • Some bacteria are inhibited by the presence of the blood.
  • Some bacteria, including Haemophilus influenza will only grow if the blood cells have been lysed, releasing intracellular nutrients. The lysed blood is a darker brown colour and is called ‘chocolate agar’.
67
Q

Describe the physical properties of agar and explain why they make it suitable for it’s function

A
  • It melts when heated to around 85DC, and yet when cooled it does not solidify to gel until 34-42
  • DC
  • Agar is clearer than gelatine
  • It resists digestion by bacterial enzymes
  • The use of agar allows the creation of a medium that can be inoculated at 40oC in its cooled molten state and yet incubated at 60oC without melting.
68
Q

Describe the susceptibility part of M,C&S (Microscopy, culture, antibiotic susceptibility) of bacteriology

A

Any organism that we consider ‘significant’, we often the see what type of antimicrobial will kill them

69
Q

What is CSF and what is it’s importance in bacteriology?

A
  • Cerebrospinal fluid
  • Th fluid surrounding brain and spinal chord
  • In cases of meningitis, there is an increase in the number of white cells in the CFS
  • We can look at CFS under a microscope, on a slide to support or discount the possibility of an infection like meningitis
70
Q

How do most bacterial investigations happen? What are the other ways?

A

M,C &S = main way

Other ways:

  • Antigen detection
  • Nucleic acid detection
71
Q

Describe the antigen detection part of bacteriology

A

The antigen is something on the target that the body’s immune system would respond to

We can use antibodies that have been developed which are often labelled with chemicals which show up the antibody-antigen reaction

72
Q

Describe the nucleic acid detection aspect of bacteriology

A
  • Molecular tests such as PCR - polymerase chain reaction, to amplify the DNA that we are looking for, if it’s present in the sample
73
Q

What are the components of virology?

A
  • Antigen detection (the virus)
  • Antibody detection (the patient’s response)
  • Detecting viral nucleic acid (DNA or RNA)
74
Q

What used to be used routinely in viral laboratories?

A

Viral culture

75
Q

Why is viral culture not routinely used anymore (apart from in specialist research)?

A
  • Takes several days to get a positive result
  • Takes a lot of skill
  • Expensive
76
Q

Describe how antigen detection of the patient works

A
  1. There is a small well in plastic tray
  2. Bottom of well is coated with antibodies against the virus
  3. Tissue sample (potentially containing the virus is added to well
  4. Virus is allowed to attach to antibody
  5. Fluid is washed out and virus stays stuck to antibody
  6. Another antibody is added to thee tray
  7. Attached to that antibody might be an enzyme
  8. The tray is washed again,
  9. If there’s any virus in there, we need to make it visible
  10. We do that by adding a chemical which the enzyme acts on, and that chemical changes colour to produce a signal (ELISA)
77
Q

What technique do antigen and antibody detection use?

A

ELISA ( Enzyme linked immunosorbent assay)

78
Q

Label A-F, which shows the components of an antigen detection test (to detect viral antigens)

A
79
Q

Describe antibody detection (patient’s response) in virology

A

Looking for the presence of antibody in patient:

  1. There is a small well in plastic tray
  2. Bottom of well is coated with antigens - Maybe particles of virus
  3. Patient’s sample is added
  4. Antibody from patient is allowed to bind to the antigen
  5. Residual sample is washed out and patient antibody stays stuck to antigen
  6. Another antibody to the patient’s antibody is added to the tray
  7. Attached to that antibody is an enzyme
  8. The tray is washed again
  9. If there’s any antibody in the patient’s sample present, we need to make it visible
  10. We do that by adding a chemical which the enzyme acts on, and that chemical changes colour to produce a signal (ELISA)
80
Q

Label A-E, which shows the components of an antibody detection test (to detect antibodies in the patient )

A
81
Q

What may we sometimes do when looking for the presence of an antibody in a patient?

A
  • Take 2 samples:
  • One when the patient is first unwell
  • Another one a week or 2 later
82
Q

Why may we take 2 samples if looking for the presence of an antibody in a patient?

A

Because the patient may take several days/a week or 2 to produce sufficient antibodies.

So by taking 2 sample (one when the patient is first unwell and another a week or 2 later, we look for an increase in antibody concentration

If we see a significant increase in antibody concentration, it indicates that the patient had a recent infection

83
Q

In the vein of detecting viral nucleic acid, what nucleic acid do we look for in:

a) Bacteria
b) Viruses

A

a) The only nucleic acid you look for in bacteria is DNA
b) In viruses it can differ in their nucleic acid content - some contain DNA some contain RNA

84
Q

What can PCR be used for?

A
  • Detection of viral nucleic acid, regardless of whether it’s DNA or RNA
  • (If it’s RNA, we need to convert it to DNA first before using the PCR)
85
Q

Who is involved in managing infections?

A
  • All clinicians encounter patients with infections, even if infection isn’t the primary interest of that clinician
  • Specialties whose primary interest is infection:
  • infectious diseases physicians
  • medical microbiology and virology
  • genitourinary medicine clinicians (special interest in sexually transmitted infections)
  • Public health physicians involved in health protection (e.g. epidemiologists)
86
Q

What must all those involved in healthcare be aware of?

A

All those involved in health care must be aware of the possibility of infections in patients whether it is the primary cause of their symptoms or as a consequence of another condition.

Thus every Doctor meeds to know basic knowledge in infection process and how to manage them (diagnose and treat)

87
Q

Give some examples of hot topics in infection

A
  • new pathogens emerging all the time (like Covid-19)
  • antimicrobial resistance so we are finding it increasingly difficult to treat even very common illnesses with antibiotics
  • healthcare infections (infections caught within the hospital setting e.g. Covid-19)
  • re-labelling of established diseases as infections (e.g. stomach ulcers were found to be due to infection)
88
Q

Give some explanations as to why countless microorganisms have emerged over the last few decades

A
  • Changes in human behaviour
  • Moving to parts of the world where humans haven’t traditionally lived
  • Emerging pathogens from animals being disrupted by climate change
89
Q

Describe the usual nature of exotoxins

A
  • Usually heat labile proteins secreted by certain species of bacteria (usually gram positive) which diffuse into the surrounding medium
  • Usually highly toxic and highly antigenic
  • Are often enzymes and usually have specific receptors to which they can bind
90
Q

Give an example of exotoxins

A
  • Toxins produced by Staphylococcus aureus.
91
Q

Describe the nature of endotoxins

A
  • heat stable lipopolysaccharide-protein complexes which form structural components of cell wall of Gram Negative Bacteria
  • Liberated only on cell lysis or death of bacteria.
  • Usually only mildly toxic and antigenic and do not bind to specific receptors.
92
Q

Give an example of endotoxins

A

Example – toxins produced by Escherichia coli.

93
Q

Describe lipopolysaccharide

A

LPS consists of:

  • Polysaccharide, composed of repeating sugar subunits (O antigen), which protrude from the exterior cell surface
  • a core polysaccharide
  • a lipid component called lipid A that is responsible for the toxicity of this molecule
94
Q

What is commonly used for the culture of bacteria?

A

Agar plates

95
Q

Describe the culturing of bacteria in the lab

A
  • Sometimes cultured using a liquid medium
  • But agar plates are easier to handle
96
Q

Describe the physical properties of agar and explain why they are useful for it’s purpose

A
97
Q

What colour is the standard agar plate, and why?

A

Red due to the addition of horse and sheep blood