Microbiology COPY Flashcards

1
Q

Define Pathogen?

A

Organism that causes or is capable of causing disease

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2
Q

Define a Commensal?

A

Organism which colonises the host but causes no disease in normal circumstances

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3
Q

Define an opportunistic pathogen?

A

Microbe that only causes disease if hosts defenses are compromised

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4
Q

Define Virulence?

A

The degree to which an organism is pathogenic

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5
Q

Define Asymptomatic carriage?

A

When a pathogen is carried harmlessly at a tissue site where it causes no disease

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6
Q

What test can be done to distinguish between staphylococcus and streptococcus?

A

The catalase test; detects the presence of catalase enzyme using hydrogen peroxide.

Staph = catalase + ve

Strep = catalase - ve

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7
Q

How do staphylococcus appear under the microscope?

A

Clusters of cocci

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8
Q

How do streptococcus appear under the microscope?

A

Chains of cocci

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9
Q

What colour are Gram positive and Gram Negative bacteria under a microscope?

A

Gram positive - Purple/blue

Gram negative - pink/red

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10
Q

What kind of bacteria are gram positive mostly?

A

Cocci

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11
Q

What kind of bacteria are gram negative mostly?

A

Bacili

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12
Q

What stain would you use to detect acid fast organisms?

A

Ziehl-Neelsen stain
Used for Mycobacteria (eg. M.tuberculosis)
Appear pink

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13
Q

What stain would be used for Mycobacteria tuberculosis?

A

Ziehl Neelsen stain
Because it is an acid fast bacilli (AFB)

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14
Q

What is the cell wall structure of a gram positive bacteria?

A

Capsule
Large peptidoglycan layer
Phospholipid membrane

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15
Q

What is the cell wall structure of a gram negative bacteria?

A

Capsule
Outer membrane with endotoxin - such as LPS
Small peptidoglycan layer
Phospholipid inner membrane

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16
Q

Describe the characteristics of Gram positive bacteria?

A
  1. Single membrane
  2. Thick peptidoglycan layer

Often cocci

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17
Q

Describe the characteristics of Gram negative bacteria?

A
  1. Double membrane
  2. Small peptidoglycan area
  3. LPS (endotoxin area)

often bacilli

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18
Q

What temperature ranges and pH can bacteria grow in?

A

Between -80°C → +80°C

Between pH 4 → 9

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19
Q

What is an endotoxin?

A

component of the outer membrane of gram-negative bacteria e.g. LPS in Gram negative bacteria

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20
Q

What is an exotoxin?

A

secreted proteins of Gram positive and Gram negative bacteria

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21
Q

What are the features of Exotoxin?

A

Protein
Specific
Heat liable (changes in heat)
Strong antigenicity
Can be converted to toxoids

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22
Q

What are the features of Endotoxin?

A

Lipopolysaccharide (LPS)
Non-specific
Heat stable
Weak antigenicity
Not converted to toxoids

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23
Q

What are the 3 ways that bacteria can transfer genes?

A

Transformation - via plasmids
Transduction - via bacteriophages
Conjugation - via sex pilus

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24
Q

How does transformation bacterial gene transfer work?

A

Horizontal gene transfer where some bacteria take up foreign genetic material from the environment and release this as plasmids taken up by other bacteria

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25
How does transduction bacteria gene transfer work?
Genetic recombination where genes from a host cell (bacterium) are incorporated into a bacterial virus genome (bacteriophage) and then transferred to another bacteria when the bacteriophage infects another cell.
26
What are obligate intracellular bacteria?
Bacteria that can only grow inside a host cell Therefore we cannot grow them on agar plates
27
Give examples of obligate intracellular bacteria?
Chlamydia Rickettsia Coxiella
28
How would you carry out a gram stain?
ComeInAndStain 1. Apply primary stain - crystal violet (purple) - to heat fixed bacteria 2. Add iodine which binds to crystal violet and helps fix it to the cell wall 3. Decolourise with ethanol or acetone 4. Counterstain with safranin (pink)
29
What test is used to distinguish between different streptococcal bacteria?
Blood agar haemolysis
30
What are the different results of blood agar haemolysis and what do they mean?
alpha haemolysis - partial (appears green) = Streptococcus pneumonia or Viridans group streptococcus Beta haemolysis - full = Group A,B,C,G strep - Requires further Lancefield serotype test to determine species Gamma haemolysis - none = Enterococcus
31
What test is done for the alpha haemolytic streptococcus to distinguish the species?
Optochin Test Optochin sensitive - Streptococcus pneumonia Optochin Resistant - Viridans group Streptococcus
32
Give some examples of different Lancefield group streptococci?
Group A - Streptococcus pyogenes Group B - Streptococcus agalactiae
33
What type of bacteria are grown on MacConkey Agar?
Gram negative Bacilli
34
What is MacConkey Agar?
Contains bile salts, lactose and a pH indicator If an organism ferments lactose - lactic acid is produce and the agar will appear red/pink.
35
What are the main bacteria that give a positive result on MacConkey agar?
Escherichia Coli Klebsiella pneumoniae Enterobacter
36
What are the main bacteria that give a negative result on MacConkey agar?
Salmonella Shigella Proteus Yersinia Pseudomonas
37
Are streptococci mainly aerobic or anareobic?
Aerobic
38
What are the 3 methods to classify streptococcus?
Haemoloysis on blood agar Lancefield typing (sero grouping based on surface carbohydrate antigens) Biochemical properties
39
What does a facultatively anaerobic bacteria mean?
Means that the bacteria likes aerobic conditions mainly but can adapt if conditions tun anaerobic
40
Give an example of a bacteria that is facultatively anaerobic?
Streptococcus pyogenes
41
What haemolysis classification does Streptococcus pyogenes fall into?
beta haemolysis Group A strep
42
What antibiotic would be used against streptococcus pyogenes?
Penicillin
43
What are some associated conditions caused by S.pyogenes?
Wound infections - cause cellulitis Tonsilitis and Pharyngitis Otitis media Impetigo Scarlet Fever
44
Wha are some complications caused by S.pyogenes infection?
Can cause rheumatic fever Can cause glomerulonephritis
45
What are the virulence factors of S.pyogenes?
Streptokinase Streptolysin O and S Erythrogenic Toxin M Toxin
46
Where is Streptococcus pneumoniae often found as a commensal organism?
In the oropharynx in roughly 30% of the population
47
What are the associated conditions caused by S.pneumoniae?
Pneumonia Otitis media Sinusitis Meningitis
48
what predisposing features can increase your risk of S.pneumoniae infection?
Impaired mucus trapping (caused by viral infection) Hypogammaglobulinaemia (low antibody count) Asplenia - Absence of normal spleen function
49
What are the virulence factors of S.pneumoniae?
Capsule - polysaccharide Inflammatory wall constituents - Teichoic acid and peptidoglycan Cytotoxin - pneumolysin.
50
How does S.pneumoniae respond to the Optochin test?
They are sensitive to it so they die.
51
What is the name given to oral streptococci?
Viridans group streptococci
52
What is the most virulent group of the Viridans group streptococci?
S.milleri
53
What are the associated conditions caused by viridans group strep?
Dental caries and abscesses Infective endocarditis Deep organ abscesses
54
Are staphylococcus mainly aerobic or anaerobic?
Mainly aerobic
55
What is the most important stapyhlococcus?
Staphylococcus aureus
56
What is the habitat of staphylococcus aureus? How is it spread?
Nose and skin Spread via aerosol and touch
57
What result would S.aureus give in the coagulase test?
Positive result
58
What is the purpose of bacteria possessing the coagulase enzyme?
This means that they can clot the blood plasma around the bacteria to attempt to protect themselves from phagocytosis
59
How would S.aureus appear on blood agar?
yellow colonies
60
What is MRSA?
Methicillin (flucloxacillin) Resistant Staphylococcus aureus
61
What drugs are MRSA typically resistant too?
- β-lactams - Gentamicin - Erythromycin - Tetracycline
62
What main drug would you give to treat MRSA infection?
Vancomycin
63
What are the 4 virulence factors of S.aureus?
1. Toxins: pore-forming e.g. **α-haemolysin and PVL** = causes hemorrhagic pneumonia 2. Proteases: **exfoliatin** = scalded skin syndrome 3. Toxic shock syndrome toxin (TSST): stimulates cytokine release 4. Protein A: a surface protein which binds Ig's in wrong orientation so they can't be recognised by the immune system.
64
What are the associated conditions caused by Staphylococcus aureus?
Wound infections Abscesses Impetigo Septicaemia Osteomyelitis Pneumonia Endocarditis Toxins could also cause toxic shock syndrome and food poisoning
65
What result would Staphylococcus epidermidis give on the coagulase test?
Negative result
66
What does S.epidermidis look like on blood agar?
White/colourless colonies
67
What is the virulence factor of S.epidermidis?
Its ability to form persistent biofilms
68
Where are the likely sites of infection for S.epidermidis?
Prostheses Catheters Mainly affects immunocompromised individuals
69
What are the associated conditions caused by Staphylococcus saprophyticus?
Acute cystitis
70
What are the virulence factors of S.saprophyticus?
Haemagglutinin - adhesion to cell Urease enzyme - cause kidney stones
71
What is the major Corynebacterium species that can cause disease?
C.diphtheriae
72
How does C.diphtheriae infection present?
child with severe sore throat and fever for 2 days Lymphadenopathy in neck rapid breathing thick greyish membrane on tonsils Swab - shows irregular gram positive rods Stain shows metachromatic granules All leads to C.diphtheriae
73
What can we use to treat C.diphtheriae?
Anti-toxin Erythromycin
74
How do we grow C.diphtheriae in the lab from a throat swab?
Grow it in the presence of potassium tellurite This will kill other types of bacteria except corynebacterium
75
How is C.diphtheriae spread?
Via droplets
76
How can we prevent C.diphtheriae spread?
Vaccination Toxoid vaccine
77
What test could be done to further distinguish between staphylococci bacteria.
Coagulase test; looks at whether a fibrin clot is produced
78
What bacteria would be coagulase positive and negative?
Positive - S.aureus Negative - S.epidermidis, S.saprophyticus
79
What are the 4 major phyla of Gram negative bacteria?
Proteobacteria Bacteroidetes Chlamydiae Spirochaetes
80
What is the morphology of proteobacteria?
All gram negative bacilli (except Neisseria (diplococci) and Campylobacter/helicobacter (spiral))
81
What bacteria fit in the phyla proteobacteria?
Enterobacteriaceae Vibrio cholerae Pseudomonas aeruginosa Haemophilus influenzae Legionella pneumophila Bordetella pertussis Neisseria Campylobacter Helicobacter pylori
82
What is the morphology, respiration and habitat of the Enterobacteriaceae
Rods - most have flagellum Facultatively anaerobic Some species will colonise the gut - both commensal and pathogenic
83
What bacteria fit in the phyla proteobacteria?
Enterobacteriaceae Vibrio cholerae Pseudomonas aeruginosa Haemophilus influenzae Legionella pneumophila Bordetella pertussis Neisseria Campylobacter Helicobacter pylori
84
What are the different species of the Enterobacteriaeceae?
Escherichia coli Shigella Salmonella Proteus mirabilis Klebsiella pneumonia
85
What is Escherichia coli?
A commensal bacterium that is abundant as a facultative anaerobe They have a flagella
86
What antigens would be found on E.coli?
1. O antigen: part of LPS 2. K antigen: capsule 3. H antigen: flagellin
87
What are the associated infections caused by E.coli?
1. Wound infections (surgical) 2. UTIs (cystitis; ~80% of female UTIs - faecal source or sexual activity; catheterisation - most common nosocomial infection) 3. Gastroenteritis 4. Traveller's diarrhoea 5. Bacteriemia 6. Meningitis (infants) - rare in the UK
88
What are the major pathogenic types of E.coli?
ETEC - Enterotoxigenic Escherichia coli EHEC - Enterohaemorrhagic Escherichia coli EPEC - Enteropathogenic Escherichia coli STEC - Shiga toxin producing Escherichia coli
89
What is ETEC?
Enterotoxigenic Escherichia coli An E.coli that produces special toxins that stimulates the lining of the intestines causing them to secrete excessive fluid. This results in watery diarrhoea - Travellers Diarrhoea
90
What are the toxins produced by ETEC?
LT and ST enterotoxin
91
How does ETEC cause travellers diarrhoea?
Heat labile ETEC toxin modifies Gs protein to a 'locked on' state. Adenylate cyclase is activated - increased cAMP. increased secretion of Cl- into the intestinal lumen, H2O follows this down an osmotic gradient results in traveller's diarrhoea.
92
What does EHEC cause?
Enterohaemorrhagic Escherichia coli Causes bloody diarrhoea
93
What is EPEC?
Enteropathogenic Escherichia coli They lack ST and LT toxins Use adhesin called intimin to bind to host cells cause watery diarrhoea
94
What are the 4 medically important species of shigella?
S.dysenteriae S.flexneri S.boydii S.sonnei
95
What is special about shigella?
It is acid tolerant and so it will not be destroyed by gastric acid
96
How is shigella spread?
Via person to person contact Via contaminated food and water
97
What are the symptoms of shigella infection?
Severe bloody diarrhoea Frequent passage of stools > 30/day small volume pus and blood in stool prostrating cramps fever
98
What is the toxin produced by shigella?
Shiga toxin
99
Describe the pathogenesis of shigella infection?
Enters through colonic M cells: In the intestine it induces self-uptake leads to macrophage apoptosis. Cytokines are released and neutrophils are attracted Causes inflammation. Shigella spread to adjacent cells.
100
What is an important complication of shigella infection?
Systemic absorption of shiga toxin will target the kidney Causes Haemolytic Uremic Syndrome (HUS) Can lead to kidney failure
101
What is the main medically important Salmonella species?
Salmonella enterica Has over 2500 serovars
102
How is salmonella spread?
Through the ingestion of contaminated food and water
103
What are the associated infections caused by salmonella infection and name the serovars responsible for them?
Gastroenteritis - Serovar Enteritidis and Typhimurium Enteric Fever -Serovar Typhimurium and Paratyphi Bacteraeima - Serovar Cholerasuis and Dublin
104
What is the pathogenesis of Salmonella infection?
1. Invasion of gut epithelium (SI) 2. Intestinal secretory and inflammatory response: serovars Enteritidis and Typhimurium - (Does NOT produce toxins) 3. Transcytosed to basolateral membrane 4. Enters submucosal Macrophages; survive and replicate within the macrophage. 5. Systemic infection due to dissemination within macrophages: serovar Typhi
105
What are the associated infections of Proteus mirabilis?
UTI - 30% of cases Opportunistic infection Can lead to pyelonephritis and sepsis
106
What is the virulence factor of Proteus mirabilis?
Urease Causes and increase in urine pH leads to calcium and magnesium phosphate precipitation forms kidney stones
107
What kind of bacteria is Klebsiella pneumonia?
Environmental - not gut It is an opportunistic pathogen and so will infect immunocompromised subjects
108
What kind of patients get infected with Klebsiella?
It is an opportunistic pathogen so will infect immunocompromised patients Including: Neonates Elderly Immunocompromised
109
What are the associated infections caused by Klebsiella pneumonia?
UTIs Pneumonia Surgical wound infection Sepsis
110
What is significant about Klebsiella?
It is MDR (multi-drug resistant) it is resistant to carbapenems - the most broad spectrum drugs
111
What is Vibrio cholerae?
The bacteria responsible for causing cholera A facultative anaerobe notorious for causing pandemics
112
How is V.cholerae spread?
Ingestion of shellfish Contamination of drinking water - due to flooding of costal areas or poor sanitation Faecal-oral route
113
Is V.cholerae spread from person to person
Not very transmissible like this as it is highly susceptible to acid and therefore cannot survive in the stomach for long periods
114
What are the symptoms of V.cholerae infection?
Voluminous watery stools (secretory diarrhoea) - rice water stools Can lose 20L of fluid/day Dehydration leads to hypovolaemic shock which causes death No blood or pus or fever - no invasion or damage to mucosa
115
What is the treatment for cholera?
Oral rehydration therapy (ORT)
116
What is the pathogenesis of cholera?
TCP pili - required for colonisation Cholera toxin - causes Gs subunit to be locked on uncontrolled cAMP production increase PKA Increased activity of CFTR channel Loss of Cl- and Na+ Water follows and massive H2O loss
117
What is Pseudomonas aeruginosa?
Ubiquitous free-living aerobe Motile - has a flagellum opportunistic Difficult to treat - MDR
118
What are the associated infections caused by P.aeruginosa?
Acute: burns/surgical wounds UTI keratitis Systemic: Sepsis ICU: Pneumonia - leading cause of pneumonia in ICU Chronic: Patients with CF
119
What is Haemophilus influenzae?
Exclusively human parasite opportunistic infection Fastidious - requires chocolate agar to culture non-motile
120
Where is Haemophilus influenzae often found on the body?
Nasopharyngeal carriage in 25-80% of the population
121
What are the associated infections caused by H.influenzae?
Meningitis - 5-10% of cases at <5yrs bronchopneumonia Epiglotitis, Sinusitis, Otitis media Bacteraemia Pneumonia in patients with CF, COPD, HIV
122
What are the virulence factors of H.influenzae?
Capsule LPS
123
What are some facts about Legionella?
causes severe disease - 15-20% mortality Fastidious - cultured on charcoal agar
124
How is Legionella spread?
air conditioning shower heads nebulisers humidifiers
125
What are the associated infections caused by Legionella?
Legionnaires disease - severe inflammatory pneumonia
126
How is Bordetella pertussis spread?
Aerosol transmission high contagious
127
What is the major associated condition caused by Bordetella pertussis?
Whooping Cough (pertussis) Caused by the Pertussis toxin
128
What are some facts about Neisseria?
Non-flagellated gram negative diplococci Fastidious Obligate human pathogen
129
What are the 2 medically important species of Neisseria?
Neisseria meningitidis Neisseria gonorrhoea
130
How is N.meningitidis spead?
Via aerosol transmission
131
Where is N.meningitidis infections common?
In universities In barracks
132
What are the virulence factors of N.meningitidis?
Capuse LPS
133
What is the pathogenesis of N.meningitidis infections?
Exists in the nasopharynx Crosses nasopharyngeal epithelium and enters the blood stream Can cause low level bacteraemia (asymptomatic) or full sepsis (high mortality if not treated) Can cross BBB and enter CSF or subarachnoid space Lead to invasion of the meninges (meningitis)
134
What is gonorrhoea?
The second most common STD worldwide
135
How is N.gonorrhoea spread?
Person to person contact only Sexually transmitted
136
What are the associated infections caused by N.gonorrhoea?
Infections can be asymptomatic Gonorrhoea Urethritis - In women can lead to PID (pelvic inflammatory disease) Proctitis, gingivitis, pharyngitis Conjunctivitis
137
What are the virulence factors of N.gonorrhoea?
LPS Twitching motility pili
138
Give some facts about Campylobacter?
spiral rods Microaerophilic - need low O2 levels and requires CO2
139
What are the 2 medically important Campylobacter species?
C.jejuni C.coli
140
What are the associated infections caused by Campylobacter?
Most common cause of food poisoning -undercooked poultry, cattle, unpasteurised milk Causes mild to severe diarrhoea - often with blood infection is mild but can be severe in immunocompromised Px
141
What are some facts about Helicobacter pylori?
Proteobacteria Microaerophilic - low O2 Spiral shaped
142
Is helicobacter spread?
No - it is not spread but exists in the gastric mucus of roughly 50% of the global population Therefore only a fraction of people develop disease
143
What are the associated infections caused by Helicobacter pylori?
Gastritis Peptic ulcer disease - causes 80-90% of ulcers Implicated in 10% of gastric adenocarcinomas and MALT lymphoma
144
What is the morphology of the bacteroidetes?
Rod shaped bacili
145
What is the most common Bacteroides infection?
Bacteroides fragilis Most common cause of anaerobic infections
146
Give some facts about Bacteroides?
Non motile rods obligate anaerobes Make up commensal flora of large bowel Most abundant flora - 30-40% of total flora
147
What are the associated infections caused by bacteroides?
opportunistic Only occur with tissue injury - surgery, perforated appendix or ulcer
148
What is the morphology of Chalmydiae
Round - elementary bodies Pleiomorphic - reticulate bodes Small non motile
149
What kind of bacteria is Chlamydiae?
Gram neg Obligate intracellular parasite
150
What is the pathogenesis of Chlamydiae?
Unique growth cycle - 2 developmental stages 1. Elementary bodies - infectious and will enter cells via endocytosis 2. Reticulate bodies - Replicative (non-infectious), will acquire nutrients from host Reticulate bodies are converted back to elementary bodies to be release and infect other cells
151
What are the 2 medically important genus and species within of chlamydiae?
Chlamydia: C.trachomatis Chlamydophila: C.pneumonia C.psittaci
152
What are the associated infections caused by Chlamydia trachomatis?
Trachoma - blindness Genital tract STD - Most common STD Usually, asymptomatic Lympho-granuloma venereum (LGV)
153
What are the associated infections caused by C.pneumonia?
Respiratory tract infection - mild pneumonia
154
What proportion of N.gonorrhoea infections are asymptomatic?
Men - 10% Women - 50%
155
What is the morphology of Spirochaetes?
Spiral/helical
156
What are the medically important Spirochaetes?
Borrelia burgdorferi - Lime diesase Treponema pallidum - Syphilis
157
What is the associated infection caused by Borrelia burgdorferi and how is it spread?
Lyme disease (300 cases in UK) Spread via tick bites
158
What is the pathogenesis of Borrelia burgdorferi?
1. Bacteria infects small mammals i.e. rodents 2. Tick larvae acquire from the rodents; transmitted to humans by nymphs. → bull's eye rash and flu-like symptoms.
159
What is the associated infection caused by Treponema pallidum?
Syphilis (STD) (2800 cases in UK)
160
What is the culture medium to grow Borrelia burgdorferi?
In a medium containing rabbit serum
161
What is the pathogenesis of Treponema pallidum?
Primary stage: Localised infection: ulcer (chancre) that occurs days-weeks post infection; highly transmissible Secondary stage: ~50% cases: systemic - skin, lymph nodes, joins, muscles occurs 1-3months post infection; highly transmissible Tertiary stage: ~30% cases: granuloma (gummas) in bone and soft tissue: Cardiovascular syphilis: aorta Neurosyphilis: brain and spinal cord Occurs several years post infection; non-infectious stage
162
What is the culture medium used to grow Treponema pallidum?
Cannot grow on cultures Detected using serology
163
What is a dermatophyte?
A fungi that requires keratin for growth
164
What are the forms of fungal infection?
- Skin infection - Good prognosis - tends to be mild but occasionally debilitating - Mucosal infection - Good prognosis - tend to be mild but occasionally debilitating - Invasive infection (including wound infection) - Poor prognosis - can be life threatening even with ideal medical care
165
Are fungal infections primary pathogenic or opportunistic normally?
Normally opportunistic
166
What causes fungal skin infections?
Dermatophytes
167
Where do dermatophytes get nutrients from?
Keratin in the skin. they are associated with the epidermis as the can feed off the dead skin tissue for keratin
168
When might a fungus become invasive?
in immunocompromised patients
169
What part of the immune system is required to clear fungal infections?
Innate - macrophages
170
What is eye karatitis?
Ulcerative corneal infection (also called mycotic keratitis or keratomycosis)
171
What agents cause eye keratitis?
Fungus Bacteria
172
What can eye keratitis lead to if left untreated?
Reduced vision or blindless (second most common cause of blindness behind cataracts)
173
Why is candidiasis a cause for concern?
It is treatment resistant
174
What are the main species of Candidiasis?
Candida albicans Candida glabrata Candida tropicalis
175
Where is aspergillosis found?
An environmental organism
176
How does aspergillus infection occur?
From spores - these are inhaled and infection occurs through the lungs (it is a conidial fungas)
177
What are the 2 main asperigllus species?
Aspergillus fumigatus Aspergillus nidulans
178
What is allergic aspergillus a complication of?
Asthma Cystic fibrosis Sinusitis
179
When is Aspergillus invasive?
In immunocompromised patients
180
What is chronic pulmonary aspergillosis?
A difficult to treat ongoing infection. If there is a significant underlying lung disease then this can lead to a reduced lung function making this infection difficult to clear leading to it becoming chronic.
181
What disease does a pneumocystis infection cause?
Pneumocystis pneumonia
182
What species of Pneumocystis causes Pneumocystis pneumonia?
Pneumocystis jirovecii An obligate human parasite of the lung
183
What kind of people get infected with Pneumocystis?
Immunocompromised
184
Where is cryptococcus found?
In the environment
185
What are the 2 main species of cryptococcus?
Cryptococcus neoformans Cryptococcus gattii Tends to only infect immunocompromised patients
186
What is the aim of antimicrobial drug therapy?
To achieve inhibitory levels of agent at the site of infection without host cell toxicity
187
What does antimicrobial drug therapy rely on?
Identifying molecules with selective toxicity for organism targets
188
List the factors required for antifungal drug selective toxicity?
- Target does not exist in humans - Target is significantly different to human analogue - Drug is concentrated in organism cell with respect to humans - Increased permeability to compound - Modification of compound in organism or human cellular environment - Human cells are "rescued" from toxicity by an alternative metabolic pathways
189
What are the main structural differences between human and fungal cells?
Fungi have cell walls These cell walls are comprised of ergosterol
190
What are the 2 classes of fungal cell membrane active agents?
Polyenes Ergosterol Synthetic pathway inhibitors
191
Give 2 examples of polyenes?
Amphotericin - broad spectrum Nystain - Topic treatment
192
What is the mechanism of action of polyenes?
Form a pore in the ergosterol membrane 10x less affinity for cholesterol in mammalian membranes
193
What are some unwanted effects of using polyenes on mammalian cells?
Salt shifts
194
What is the mechanism of action of Ergosterol synthetic pathway inhibitors?
Dose dependent inhibitors of 14alpha-sterol demethylase Secondary targets in the synthetic pathway inhibited by triazoles
195
Give 5 examples of Azoles and the fungi they act on
Fluconazole - Candida and Cryptococcus Itraconazole - Aspergillus Voriconazole - Invasive Aspergillus Posaconazole and Isavuconazole - Zygomycetes
196
What are some side effects of Azoles?
liver dysfunction GI symptoms: 10% of patients may discontinue drugs because of it Nausea vomiting pain Diarrhoea
197
What class of drugs are fungal cell wall acting agents?
Echinocandins
198
What is the mechanism of action of Echinocandins?
Inhibit 1,3-beta-glucan synthase
199
Give 3 examples of Echinocandins
Caspofungin Micafungin Anidulafungin
200
What fungi do Echinocandins tend to work on?
Susceptible yeasts Mould
201
How are Echinocandins administered and why?
Via intravenous Poor oral bioavailability
202
What are the main Mycobacteria of medical importance?
Mycobacteria tuberculosis Mycobacteria leprae
203
How are mycobacteria classified in Gram staining?
They sit with the Gram-Positive bacteria family They however do not stain on Gram stain Require Ziehl-Neelsen stain
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Why do Mycobacteria not stain on Gram stain?
The composition of their cell wall makes it impervious to staining They have a high lipid content with Mycolic acids Acid-Fast Bacteria
205
What stain is used to stain Mycobacteria?
Ziehl-Neelsen
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Are Mycobacteria: Spore forming Aeorobic/Anaerobic Motile?
Mycobacteria are Non spore forming Aerobic Non motile
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What is the significance of the Waxy cell wall on Mycobacteria?
Difficult to target with antibacterial agents It allows them to survive inside macrophages at low pH environments
208
What is the growth rate of Mycobacteria?
Very slow Weeks
209
What about the biology of Mycobacteria makes Mycobacteria difficult to treat?
Slow reproduction time Slow growth in humans - gradual onset of disease Slow growth in culture - increased time to make diagnosis Slow response to treatment - cannot target fast reproduction times like other bacteria
210
What happens after a macrophage phagocytoses a Mycobacterium?
Bacterium is adapted to the intracellular environment It can withstand phagolysosomal killing and will escape into the cytosol.
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How can macrophages kill mycobacteria?
Release microbicidal molecules to kill the bacteria They then present the antigen on MHC II molecules This is detected by CD4 T cells CD4 cells secrete IFNy andTNFa to activate intracellular macrophage killing
212
What composes a granuloma?
Infected macrophage in the centre Other recruited Macrophages aggregated together (aggregates of epithelioid histocytes) Surrounded by Lymphocytes (T and B cells)
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What is the function of a granuloma? What is a problem with this?
It will wall off the bacteria However this can create a niche for the bacteria to enter latency and survive
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What cell type is responsible for walling off the granuloma?
Fibroblasts
215
What conditions can make granulomas unstable and at risk of rupture?
CD4 depletion caused by HIV TNFa depletion caused by therapies against RA or organ transplant
216
What are the 2 ways to diagnose Mycobacteria with culture?
Solid culture: Microscopy positive 2-4 weeks Microscopy negative 4-8 weeks Liquid culture: 1-3 weeks
217
What other way can be used to diagnose Mycobacteria without culture? What are the benefits of this?
Nucleic Acid Detection: Uses PCR based testing Faster results Can detect for resistance Sensitive and very specific
218
How can TB be diagnosed using a skin prick test?
The Mantoux test: Intradermal injection of purified TB protein derivatives Induced swelling and redness is a positive result
219
What is the treatment for tuberculosis?
4 Drugs: (RIPE) Rifampin - 6 months Isoniazid - 6 months Pyrazinamide - 2 months Ethambutol - 2 months
220
What is the length of time for treatment of TB?
4-9 months of combination therapy
221
Why are second line drugs sometimes used in TB?
Antibiotic resistant strains
222
What is the issue with the long length of time of TB treatment?
Side effects Hepatotoxicity Peripheral Neuropathy Optic Neuritis
223
What are the different types of resistance TB strains?
MDR TB - resistant to multiple first line drugs EDR (extensively drug resistant) - resistant to second line drugs Totally drug resistant - TB resistant to treatment
224
What are the routes of infection of TB?
Aerosol Patient to Patient Transfer
225
What is primary TB?
- Initial contact made by alveolar macrophages - Tuberculosis evades killing by macrophage - Use macrophage to get transported through the lymphatics to the hilar lymph node
226
What is latent TB?
- Primary infection contained but cell mediated immunity persists - Therefore in latent TB there is no clinical disease - But the response to TB can be measured in tuberculin skin test
227
What is Pulmonary TB?
- Failure of immune system leads to the clinical presentation of disease: - Granulomas form around bacilli that have settled in the apex of the lung - In the apex there is more air and less blood - More air for bacteria - Less blood access for white blood cells to clear infection
228
What happens as a result of a latent TB granuloma rupturing?
Abscess formation Necrosis occurs in the centre of the granuloma (caseous) Caseous (cheesy) material gets coughed up
229
When does pulmonary TB occur?
Immediately after primary infection After latent activation
230
Following TB activation, where can it spread to?
Other areas of the lung to create other TB lesions Other body tissues: TB meningitis Miliary TB Pleural TB Bone and joint TB Genitourinary TB
231
What are the risk factors for the reactivation of dormant TB?
Age - infants, young adults, elderly Malnutrition Intensity of initial exposure Immunosuppression
232
Define a virus?
An infectious obligate intracellular parasite Comprised of genetic material (DNA OR RNA) Surrounded by a protein coat or membrane
233
What viruses prevalent in the UK can cause miscarriages or birth defects?
Cytomegalovirus (CMV) Varicella Zoster Virus (VZV) Herpes Simplex Virus (HSV) Rubella
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What viruses in the UK can cause outbreaks?
Influenza Measles Mumps Norovirus
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What viruses in the UK can cause Cancer?
Epstein Barr Virus (EBV) - Lymphoma Hepatitis B/C - Hepatocellular Carcinoma Human Papilloma Virus (HPV) - Cervical/anal cancer HIV - Increase risk of contracting other cancer causing viruses
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What are some characteristics of a virus?
Grow inside living cells - replicate inside host machinery Possess only one type of nucleic acid - DNA OR RNA (not both) No cell wall - Have a protein coat (capsid) or membrane lipid evenlope Inert outside of host cell Protein receptors on virus surface to allow for attachment to susceptible host cells
237
What are the different clinical presentations of viruses and give examples for each?
Acute: Symptomatic - Chicken pox caused by VZV Asymptomatic - Herpes and CMV Chronic: Hepatitis B and C HIV Latent: Reactivation of VZV causes shingles in adulthood
238
What diagnostic tests are used to identify viruses?
PCR - identifies viral genetic material Serology - detection of immunological memory of a virus Histopathology - features of viral infection Viral culture Electron Microscopy
239
What are the stages of Viral Replication?
1. Attachment to specific receptor 2. Cell entry 3. Host cell interaction 4. Replication of viral DNA into host cell 5. Assembly of virion - Translation of viral mRNA to produce Viral genome, structural proteins and non-structural proteins 6. Release of new viral particles - viral bursting (cell death) or budding/exocytosis
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How do viruses cause disease?
Direct destruction of host cells Modification of host cells Over reactivity of the immune system Damage through cell proliferation Evasion of Host defenses
241
Give an example of a virus that causes disease by destroying host cells?
**Poliovirus:** - Infects and replicates within nerves, over 4 hours - Host neuron lysis and death - Causing paralysis
242
Give an example of a virus that causes disease by modifying host cells?
**Rotavirus:** - Atrophies villi and flattens epithelial cells of the gut - Decreases small intestine surface area - Nutrients (including sugar) are not absorbed - Hyperosmotic state - sugar remains in lumen so draws in water - Profuse diarrhoea **Rotavirus is resistant to acidic pH*
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Give an example of a virus that causes disease by over activating the immune system?
**Hepatitis B:** 1. Virus infects hepatocyctes, and cause the presentation of the viral antigen on outside the hepatocyte. 2. Cytotoxic T lymphocytes recognise the antigen as foreign and kill the hepatocyte infected with virus, leading to a reduced number of hepatocytes
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What symptoms are caused by a reduced number of hepatocytes as found in Hepatitis B/C infections?
- Jaundice (increased bilirubin) - Pale stool (increased bilirubin) - Dark urine (increased bilirubin) - Right Upper Quadrant (RUQ) pain - Fever and malaise - Itching (bile salts released into body) **Hepatitis B tends to become chronic. Sustained viral replication and liver cell destruction occurs but at a lower level, presenting fewer clinical symptoms*
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Give an example of a virus that causes disease by damage through cell proliferation
**Human Papillomavirus (HPV):** 1. Acquired through direct contact 2. Partial viral replication and expression of HPV proteins - these are oncoproteins 3. Viral DNA integration into host chromosomes 4. Continous expression of oncoproteins (cancer causing proteins) causing cellular DNA mutations → dysplasia and neoplasia
246
What are the different methods of host defence evasion that viruses use?
1. Virus persistence or latency. 2. Down regulation of interferons. 3. Virus variability due to gene reassortment or mutation. 4. Prevention of host cell apoptosis. 5. Viral modulation of host defences.
247
What are the different clinical presentations of Herpes Simplex Virus (HSV)?
- Skin **Orofacial herpes** - cold sores **Genital herpes** - warts **Herpetic whitelow** - sores on the fingers **Erythema multiforme** - systemic rash across the body **Herpes gladiatorum** - rash affecting the chest - Visceral **Oesophagitis** - inflammation of the oesophagus **Pneumonitis** - inflammation of the lungs **Hepatitis** - inflammation of the liver - CNS Meningitis - inflammation of the meninges surrounding the brain Encephalitis - inflammation of the brain Transverse myelitis - inflammation across the spinal cord (can cause paralysis, sensation changes) - Eye - Conjunctivitis - Keratitis
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What is the ONLY clinical presentation of JC virus (Human polyomavirus 2)
CNS - progressive multifocal leukoencephalopathy
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What are Protozoa?
Single cell eukaryotic organisms Unicellular Can be free living or parasitic
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How are Protozoa classified? What are their classifications
Based on locomotion: Amoebaoids Sporozoa Flagellates Cilliates Microsporidia
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Give an example of an Amoeboid?
Entamoeba histolytica
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How is Entamoeba Histolytica spread?
Faeco-oral route
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How are Entamoeba Histolytica infections treated?
With Metronidazole
254
Give examples of diseases caused by flagellates?
Human African Trypanosomiasis (sleeping sickness) American Trypanosomiasis (Chagas disease) Leishmaniasis Trichomoniassis Giardiasis
255
Give examples of diseases caused by flagellates?
Human African Trypanosomiasis (sleeping sickness) American Trypanosomiasis (Chagas disease) Leishmaniasis Trichomoniasis Giardiasis
256
What are the symptoms of Human African Trypanosomiasis infection?
- Chancre - Fever - Headaches - Extreme fatigue - Lymphoadenopathy - Spenomegaly - CNS involvement (e.g. personality changes)
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How is Human African Trypanosomiasis spread?
Vector - infected via Tsetse fly
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How is Human African Trypanosomiasis diagnosed?
Blood film or CNS
259
What are the symptoms associated with American Trypanosomiasis?
- Slower illness manifestations - Headache - Fever - Lymphadenopathy - Chagoma - swelling at site of innoculation - Romana's sign - swelling around the eyes, eyelids and conjunctiva - Late disease manifestations - Dilated cardiomyopathy - Megaoesophagus - Megacolon
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What specific flagellate cause American Trypanosomiasis?
Trypanosoma cruzi
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How is American Trypanosomiasis spread?
Vector - transmitted through faeces of triatomine bug Through blood, vertical transmission and contaminated food
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How is American Trypanosomiasis diagnosed?
Visualisation of tropmastigotes on blood film Amastigoes on biopsy in chronic illness
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What symptoms are associated with Leishmaniasis?
- Cutaneous - Incubation; weeks to months - Ulcers on exposed parts of body; these heal and leaving permenant scars - Usually benign - Mucocutaneous - Partial or total destruction of mucous membranes of nose, mouth and throat cavities - Visceral - Known as Kala-Azar (black fever) - Incubation period; days to years - Associated with multi-organ failure - Associated with bone marrow suppression, lymphodenopathy, weight loss. - High mortality rat
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How is Leishmaniasis spread?
Via saliva of the female sand fly
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What symptomas are associated with Giardiasis?
Diarrhoea Cramps Bloating
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How is Giardiasis spread?
Faeco-oral route
267
How is Giardiasis diagnosed?
Stool microscopy - presence of trophozoites
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How is Giardiasis treated?
Metronidazole and tinidazole
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What symptoms are associated with Trichomoniasis in women?
- Purulent discharge - Abdominal pain - Vulvar/ cervical lesions - Dysuria - Dyspareunia
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What symptoms are associated with Trichomoniasis in men?
- Urethritis - Epididymitis - Prostatitis *Often asymptomatic*
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What specific flagellate causes Trichomoniasis?
Trichomonas vaginalis
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How is Trichomoniasis spread?
Sexually Transmitted Infection (STI)
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How is Trichomoniasis treated?
Metronidazole
274
Give some examples of diseases caused by sporozoids?
Cryptosporidiosis Toxoplasmosis
275
What symptoms are associated with Cryptosporidiosis?
- Watery diarrhoea (no blood) - Vomiting - Fever - Weight loss
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What specific sporozoid causes Cryptosporidiosis?
Cryptosporidium spp
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How is Cryptosporidiosis spread?
Water/ food bourne infection - occurs through the ingestion of mature cysts
278
How is Cryptosporidiosis diagnosed?
Acid fast staining - oocysts seen in stool sample
279
How is Cryptosporidiosis treated?
- Hydration and replacement of electrolytes - Self-limiting disese - usually lasting no more than 2-3 weeks
280
What symptoms are associated with Toxoplasmosis?
- Usually asymptomatic - severe consequences in pregnancy and immunodeficiency - Disseminated disease (particualarly affecting the eyes!) - Chorioretinitis - Retinochoroiditis - Toxoplasma encephalitis
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What specific sporozoid causes Toxoplasmosis?
Toxoplasma gondii
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How is Toxoplasmosis spread?
*Acquired through ingestion of oocytes!* - Contaminated food - Undercooked meat and shellfish - Vertical transmission - Trasmission via water/ feline species
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How is Malaria spread?
Vector; spread of Plasmodium via the bite of a female Anopheles mosquito
284
What are the five species of Malaria-causing Plasmodium?
- Plasmodium falciparum (important!) - Plasmodium ovale - Plasmodium vivax - Plasmodium malariae - Plasmodium knowlesi
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What species of plasmodium is responsible for the most number of malaria cases and what percentage is this?
P. falciparum Responsible for 75% of malaria cases in the UK
286
What non-specific symptoms and signs are associated with Malaria?
Non-specific symptoms: - Fever, night sweats and rigors - Chills - Myalgia - headache - Vomiting Signs: Pallor - due to anaemia Hepatosplenomegaly Jaundice - bilirubin released due to RBC haemolysis
287
What haemolysis specific symptoms are associated with Malaria?
*Haemolysis due to infected cell lysis and immune-mediated killing!* - Anaemia - Jaundice - Hepatosplenomegaly - Black water fever - Hb passes into urine - Monocytosis and lymphopenia - loss of WBC response - Thrombocytopenia - reduced platelets
288
How does the malarial Plasmodium cause haemolysis?
1️⃣ Parasite develops in the RBC, producing waste products and toxic factors 2️⃣ Infected cells releasing *merozoites* surface proteins and *hemozoin* into the blood 3️⃣ Stimulates macrophages to release pro-inflammatory cytokines and inflammatory mediators (TNF, IFN-y)
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How is Malaria diagnosed?
Blood film - visualisation of Trophozoite seen under light microscopy - Thick film - to detect whether person has malaria - Thin film - identify species and calculate parasitaemia percentage
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How is Malaria treated? How does this vary depending on severity of disease?
- **Uncomplicated malaria** Oral: 1. Artemether with lumefantrine (**Riamet**) 2. Proguanil and atovaquone (**Malarone**) 3. **Quinine sulphate** 4. **Doxycycline** - **Complicated or severe malaria** IV: 1. **Artesunate:** this is the most effective treatment but is not licensed. 2. **Quinine dihydrochloride**
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Explain how malaria causes disease?
- Human Liver Stage (exo-erythrocytic): - 1️⃣ Mosquito takes a blood meal, injecting the indiviual with sporozoites (infected for of the Plamsodium) - 2️⃣ Sporozoites travel in the blood and infect liver cells (hepatocytes) - 3️⃣ Sporozoites can mature into Shizoints or lay dormant as hypnozoites (in P. vivax/ P. ovale) - 4️⃣ Shizoints mature into merozoites which enter the blood and infect RBCs - ⭕ Human Blood Stage (Endo-erythrocytic): - 5️⃣ Merozoites infect RBCs - The merozoites reproduce every 48 hours. - 6️⃣ Merozoite develop into immature trophozoite. This can then go down two maturation routes: - 7️⃣ 🅰️ Trophozoite develop into Schizonts and then merozoites, which ruptures the RBC which releases more merozoites to infect other RBCs This cycle repeats every 48 hours. - ✳️ At this stage, as RBCs rupture, the individual develops cyclical fever and haemolytic clinical manifestations, such as anaemia, jaundice (bilirubinaemia), haemoglobinuria - 7️⃣ 🅱️ Some Trophozoites differentiate into *sexual stage gametocytes*
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Why do patients with malaria experience high fever spikes every 48 hours?
Due to the replication of the merozoites in the RBCs taking 48 hours at which point the RBC ruptures leading to an inflammatory response
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Explain how malaria is spread
- 8️⃣ Another mosquito takes a blood meal from this infected individual will ingest *gametocytes* - 9️⃣ Gametocytes mature into an *oocyst* - 🔟 Oocysts ruptures and release *sporozoites* - 🔟+ 1️⃣ Sporozoites are injected into the blood of a different individual - cycle.
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What is the most important Plasmodium species that causes malaria and why?
P. Falciparum Causes complicated malaria - P. Falciparum replicates rapidly and causes microcirculatory obstruction.
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What is the difference between uncomplicated and complicated malaria?
Uncomplicated: Most plasmodium-infected red blood cells get screened and destroyed by the spleen. Complicated: P.falciparum: Plasmodium falciparum avoids this fate by generating a sticky protein that coats the surface of the infected red blood cells. The protein causes the red blood cells to clump together and occlude tiny blood vessels - a process called cytoadherence. This blocks the flow of blood so that infected cells aren’t able to flow into the spleen, and it also blocks blood flow from reaching other vital organs which can cause ischaemia. This can eventually lead to organ failure (refer to complications).
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What is the pathogenesis for the obstructed microcirculation caused by P. Falciparum.
- 1️⃣ Cytoadherence Infected RBCs present membrane proteins that bind to microvascular endothelial cells in vessels - 2️⃣ Rosetting Infected RBCs also adhere to non-infected RBCs, causing small vessels to become obstructed by clumbs of RBCs - this causes hypoxia. - 3️⃣ Sequestration Microinfarcts form in major organs (brain, heart, lungs, liver, kidney) where they are able to mature and evade the immune system.
297
What are the different complications of malaria infection? What is the treatment for each complication?
Cerebral malaria - Anti-epileptic drugs Renal Failure - Fluids and dialysis Acute Respiratory Distress Syndrome (ARDS) - Oxygen, Diuretics and ventilation Bleeding - Blood products/Blood transfusion Shock - Sepsis treatment via Broad Spectrum antibiotics
298
What 2 species of the plasmodia genus lie dormant and cause late relapse of malaria?
P.ovale and p.vivax.
299
What is the treatment for malaria infection
Chloroquine
300
What are the 3 classifications of worms (helminths)
Nematodes Trematodes Cestodes
301
Does HIV affect more women or men globally?
Women more than men
302
What age group accounts for 50% of all new HIV infections worldwide?
19-24 year olds
303
What has led to the high rates of AIDs drastically dropping?
HAART (Highly Active Anti-retroviral Therapy)
304
What is the 90/90/90 target?
- Global target - 90% of people living with HIV should be diagnosed - 90% of people diagnosed with HIV started on anti-retroviral therapy - 90% of those on anti-retroviral therapy be viral suppressed
305
What is the relationship between late HIV diagnosis and prognosis?
10-fold increase in risk of death within first year of diagnosis
306
What are the HIV transmission routes?
- Blood Less common due to blood screening before blood transufsions - Sexual Most often through Heterosexual transmission despite stigma of homosexual transmission - Vertical Called this now instead of “Mother to child transmission” as it had connotations of blaming the mother
307
What does U=U mean?
- Undetectable=Untransmissible - If the viral load is undetectable in the patient's blood, they are not able to transmit the virus, even in unprotected sex - Therefore, if you take your medication properly and keep the viral load at 0 then it is not possible to pass HIV on regardless of condom use
308
What is PrEP?
- Pre-Exposure Prophylaxis - usually take tenofovir and entricitabine in one combined tablet - Take anti-retroviral therapy despite not having HIV to prevent infection - **highly effective -** much more effective than PEP
309
What is PEP?
- Post-Exposure Prophylaxis - Emergency medication taken after potential exposure to the virus - Must be started within 72 hours of exposure
310
What are the benefits to HIV testing?
- Cost-effective, testing is very cheap - Reduction in cost of social care, lost working days, benefits claimed, cost associated with further onward transmission - Gives patient access to appropriate treatment and care - Reduction of transmission
311
What are the scenarios where you would carry out an HIV test?
- Clinician indicate diagnoses - clinical indications of immunosuppressive disease - Routine screening in high prevalence locations - Antenatal screening - Screening in high risk groups - Patient initiated request for testing
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What conditions would indicate that an HIV test may be needed?
- Unexplained lymphadenopathy - Unexplained weight loss or diarrhoea, night sweats of PUO - Oral or esophageal candidiasis or hairy leukoplakia - Flu like illness, rash, meningitis - Unexplained blood dyscrasias
313
What are some recognised risk factors for HIV?
Heterosexual and homosexual sex (men to women and men to men) IVDU Multiple sexual parteners Rape Vertical transmission
314
What must be done when offering HIV testing?
- Document verbal consent given - Determine how results will be given - Do not need written consent - Do not need pre-test HIV counselling
315
What HIV screening test is preferred?
- Venous blood sample - 4th gen HIV tests detect vast majority of infections at 4 weeks - If there is a high degree of risk/suspicion of HIV infection repeat at 8 weeks if a negative result
316
What is a HIV POCT?
- Point of Care Test - Finger prick of blood - Lower sensitivity and specificity - This test is used in the community to increase access to the test, increases patient choice and case detection - Lower risk of complications and transmissions associated
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What type of virus is HIV?
Retrovirus
318
What proteins/genetic material is found within a retrovirus?
RNA genetic material Contain a reverse transcriptase enzyme
319
What virus and species is HIV-1 derived from?
Chimpanzee derived Simian Immunodeficiency virus (SIVcpz)
320
What virus and species is HIV-2 derived from?
Sooty Mangabey-derived simian Immunodeficiency virus (SIVmp)
321
what is the normal role of T cells in the immune response?
T-helper cells coordinates acquired immune response - responsible for organising, recruiting and facilitating maturation of B-antibody producing cells and CD8 (T-killer) cells.
322
What is the role of Th-1 T cells?
- CTLs produce *perforin and granulysin enzyme* that directly kills cells with antigen on. - NK cells kills any cell seen to be infected with specific foreign agent.
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What is the role of Th-2 T cells?
Produces specific interleukins (IL-4, 5, 10 and 13) whihc causes the maturation of B lymphocytes into plasma cells - Plasma cells produce specific antibodies IgG against specific antigen - Produces a rolonged and effective antibody response
324
What is the structure of the HIV virus?
Icosahedral protein capsid containing 2 RNA strands 2 enzymes: integrase and reverse transcriptase Lipid envelope with spike projections of glycoproteins GP41 and GP120 to lock onto CD4 receptors on T cells
325
What are the main cells that are infected via HIV? What other cells also can be infected?
CD4 T cells Dendritic cells, macrophages, astrocytes
326
Explain the life cycle of the HIV virus?
- 1️⃣ Glycoproteins on HIV molecule (gp160; formed of gp120 and gp41) allow it to adhere to; - CD4 receptors (gp120 and gp41 receptors) - CCR5 receptors on Macrophages -CXCR4 Receptors on CD4 T cells - 2️⃣ Once viral capsid enters cell, viral enzymes and nucleic acid are uncoated and released. - 3️⃣ Using *reverse transcriptase*, single stranded RNA is converted into double-stranded DNA. - 4️⃣ Viral DNA then is integrated into cell own DNA through the action of *integrase enzyme*. - 5️⃣ When infected cell divides the viral DNA is transcribed, producing long chains of viral proteins Whilst infected cell is replicated, the viral DNA also replicates alongside. - 6️⃣ Viral RNA is spliced and the protein chains are cleaved and reassembled by *protease enzyme* into individual proteins - these combine to form a functioning virus. - 7️⃣ The immature virus exocytosed, taking some cell membrane with it to form a new lipid envelope - 8️⃣ Once outside of the cell, the virus undergoes further maturation.
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What is the journey (Natural History) of HIV through the body?
HIV infects CD4 T cells HIV is detectable in the bloodstream around a week after initial infection 7️⃣ Production of the HIV virus increases exponentially as more and more T-cells become infected and die as the virus replicates 8️⃣ After around three weeks after infection, the viral load and p24 antigen are detectable. the immune system responds with a full adaptive immune response to try and control the new pathogen. HIV antibody is detectable 2-4 weeks in. This is seroconversion (causing acute non-specific symptoms) 9️⃣ Immune system recovery establishes control of the virus; This starts the viral latency (asymptomatic phase) as the viral load is kept at a plateau. on average, this clinical latency period last for around seven years 🔟 Progressive immunological impairment (slow decrease in CD4 T-cells) and ongoing replication of HIV in virus reservoirs eventually leads to the clinical manifestation of immunodeficiency; HIV associated opportunistic malignancy/ infection
328
What are the main events in the first few weeks after HIV infection?
Increase viral load HIV p24 antigen detected Antibodies against HIV CD8 T cell activation Seroconversion illness
329
What are some methods by which HIV transmission can be reduced/prevented?
- Consistent condom use (80-90% effective) - Male circumcision (60% reduction in infection; no benefit to female partners) - Treating STI's e.g. genital ulcers and HSV infection which increase transmission risk - Microbicide gel for women (30-40% reduction in transmission risk) - Needle and syringe exchange for IVDUs - Post-exposure prophylaxis (PeP) - Treatment as prevention (TasP) (96% reduction) - Pre-exposure prophylaxis (PreP)
330
How can paediatric HIV infection occur?
1. *In utero*: transplacental; mostly during the third trimester 2. *Intra partum*: exposure to maternal blood and genital secretions during delivery 3. *Breast milk*: ingestion of large amounts of contaminated milk
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How many adults and children are estimated to be living with HIV globally?
38 million
332
What markers are used for monitoring HIV infection?
CD4+ T cell count/ul HIV Viral load (RNA copies/ml)
333
When a patient presents with a fever, rash and non-specific symptoms, what 3 steps should you do?
- Take a sexual history - Think of HIV seroconversion illness - Tell lab to check for antigen as well
334
Which infections would a HIV test be indicated?
- Recurrent shingles - Candidiasis - (Essentially infections associated with immunocompromised patients)
335
What are the 3 main respiratory diseases associated with HIV infection?
- Bacterial (often pneumococcal) pneumonia - Tuberculosis significantly higher mortaility when you have HIV and TB - Pneumocystis jirovecii pneumonia (PCP) (most common opportunistic infection in AIDs)
336
What are the symptoms of PCP?
Fever SOB Dry cough Pleuritic chest pain Exertional drop in O2 saturations
337
How is PCP treated?
Via Co-trimoxazole
338
What are the HIV associated CNS diseases?
- CNS Mass Lesions: - Cerebral taxoplasmosis - Primary CNS Lymphoma - Tuberculoma - Meningitis: - Cryptococcal - Tuberculous (Would have CSF with raised lymphocytes, raised protein and reduced glucose. They may also have an insidious onset CNVI palsy) - Pneumococcal - Ophthalmic Lesions: - CMV - Toxoplasmosis - Choroidal Tuberculosis
339
What are the HIV associated neoplasms?
- Lymphoma - Caused by EBV - Cervical neoplasia - Caused by HPV - Kaposi's sarcoma - Caused by human Herpesvirus 8 - Hepatocellular Carcinoma - Caused by Hepatitis B/C
340
Describe the time course of HIV infection (natural history)
Acute primary infection - Acute seroconversion illness: Transient immunosuppression Fall and then rise of CD4 count. Rise of viral load Asymptomatic phase: Progressive loss of CD4 Clinical latency - may have generalised lymphadenopathy Early symptomatic HIV AIDS: Symptoms of immune deficiency
341
What is the marker for AIDS?
CD4 count less than 200/ul
342
What can influence the time from HIV infection to AIDS?
Host and viral genetic factors Rapid onset - elderly/children, high viral load
343
What are the NON-AIDS defining conditions that HIV can cause?
Oral candidiasis- Treated with Nilstat Oral hairy leucoplakia Generalised Lymphadenopathy Shingles - Treated with Acyclovir Chronic Diarrhoea
344
What are the AIDS defining conditions caused by HIV
CD4 <500 ul Mycobacteria Tuberculosis Kaposi Sarcoma - HHV8 Coccidiodomycosis Cervical Cancer CD4 <200 ul (the 3 Ps) Pneumocystis pneumonia Progressive multifocal Leukoencephalopathy Histoplasmosis CD4 < 100ul: (4 Cs) Candidiasis - eosophageal Cerebral Toxoplasmosis Cryptococcus Cryptosporidiosis CD4 < 50ul: CNS lymphoma CMV MAC infection
345
What are the symptoms associated with HIV seroconversion illness?
Abrupt onset of non-specific symptoms Significant weight loss Lethargy/depression
346
What is an important differential diagnosis of HIV seroconversion illness?
Secondary Syphilis
347
What could late HIV diagnosis lead to?
Increased transmission Increased morbidity Increased mortality
348
What are the symptoms associated with acute HIV?
- Fever, rash and non-specific symptoms - Similar to glandular fever - Diffuse symmetrical maculopapular rash
349
What are the symptoms associated with early symptomatic HIV?
- Oral/vaginal candidiasis/oral thrush - Oral Hairy Leukoplakia (associated with EBV) - VZV (shingles) with 2 or more episodes OR multiple dermatomes - Cervical dysplasia - Cervical carcinoma-in-situ - Peripheral neuropathy - Bacillary angiomatosis - Immune-mediated Thrombocytopaenic Purpura - Pelvic Inflammatory Disease - Listeriosis - Constitutional symptoms (i.e. fever or diarrhoea for more than 1 month) - persistent lymphadenopathy
350
What are the 3 classes of HIV drugs?
Reverse transcriptase inhibitors - nucleoside/non-nucleoside Protease inhibitors Fusion inhibitors
351
What drugs make up HAART?
2 Nucleoside reverse transcriptase inhibitors + 1 non-nucleoside reverse transcriptase inhibitor OR 2 Nucleoside reverse transcriptase inhibitors + 1 Protease inhibitor
352
Why in HAART are there 2 different types of drug used?
These act at different points on the HIV replication cycle
353
How does HIV develop drug resistance?
Non adherence - not taking meds Drug-drug interactions
354
What determines the class grouping of antibiotics?
Where they work: Cell wall synthesis Nucleic acid synthesis Protein synthesis Folate synthesis
355
What are bacteriostatic and bacteriocidal antibiotics?
Bacteriostatic - Prevent the growth of bacteria; defined as a ratio of Minimum Bactericidal Concentration (MBC) : Minimum Inhibitory Concentration (MIC) of > 4 Bacteriocidal - Will kill the bacteria; kills 99.9% in 18-24 hours
356
What classes of antibiotics are bacteriostatic?
- Inhibit protein synthesis - Inhibit DNA replication - Inhibit metabolism Useful in disease where its the bacteria exotoxin that's causing the symptoms as they reduce toxin production.
357
What classes of antibiotics are bacteriocidal
- Inhibit cell wall synthesis Useful in cases of poor drug penetration due to poor blood supply (endocarditis); difficult to treat infections or when we need to eradicate infections quickly (meningitis).
358
What does the MBC:MIC ratio tell us?
The Minimum Bactericidal Concentration (MBC) is the lowest concentration of an antibacterial agent required to **kill** a bacterium over a fixed time (18 hours or 24 hours), under a specific set of conditions. The Minimum Inhibitory Concentration (MIC) is defined as the lowest concentration of an antimicrobial ingredient or agent that is bacteriostatic (prevents the visible **growth** of bacteria)
359
When are antibacterial agents regarded as bactericidal?
If the MBC is no more than 4x the MIC
360
What are the 2 major determinants of antibacterial effects of antibiotics?
Concentration - How high the conc is above the MIC Time - Time that serum concentrations remain above MIC during the dose interval (t > MIC)
361
Give examples of antibiotics that are governed by concentration?
Aminoglycosides Quinolones
362
Give examples of antibiotics that are governed by time?
- β-lactams (penicillins; cephalosporins; carbapenems; monobactams) - Clindamycin - Macrolides - Oxazolidinones
363
Give 4 methods by which a bacteria can resist an antibiotic?
Change the antibiotic target - MRSA cannot bind to PBP of staphylococci Destroy the antibiotic - Staphylococci produce beta-lactamase Prevent access of antibiotic - modify membrane channel no. size. selectivity Remove antibiotic from bacteria - Export or efflux pumps
364
What are the methods by which bacteria can develop resistance?
Intrinsic - naturally resistant Acquired: Spontaneous gene mutations Horizontal gene transfer - Conjugation, Transduction, Transformation
365
Name 2 Gram-Positive resistant strains of clinical importance
MRSA - Methicillin (Flucloxacillin) resistant Staphylococcus Aureus VRE - Vancomycin resistant enterococci
366
How does MRSA have antibiotic resistance?
Staphylococcus cassette chromosome mec (SCCmec) contains the resistant gene mecA which encodes penicillin-binding protein 2a (PDP2a). Confers resistance to all β-lactams and methicillin
367
How does VRE have antibiotic resistance?
Plasmid mediated acquisition of gene encoding altered AA on peptide chain preventing vancomycin binding - promoted by cephalosporin use.
368
What mechanism do Gram Negative bacterial strains confer resistance?
Produce Beta-lactamase enzymes which hydrolise the beta-lactam ring of penicillins
369
How can we combat drugs that have beta lactamases?
Design drugs that utilise agents that inhibit beta lactamase Co-amoxiclav - Amoxicillin and Clavulanate Clavulanate inhibits the beta lactamase
370
What is ESBL?
A beta lactamase enzyme - extended spectrum beta lactamase Produced by some bacterial that allows them to hydrolise third gen cephalosporins and aztreonam
371
What is AmpC beta lactamase?
A cephalosporinase enzyme encoded by enterobacteriaceae
372
What does AmpC beta lactamase provide antibiotic resistance against?
Cephalosporins, most penicillins Beta lactamase inhibitor combinations
373
What are the 2 main classes of antibiotics that inhibit bacterial cell walls?
Beta Lactams Glycopeptides
374
What compound do beta lactam antibiotics target?
Peptidoglycan
375
Give classes of antibiotics are beta lactams?
Possess a Beta lactam ring - Penicillins - Cephalosporins - Carbapenems - Monobactams
376
What bacteria do beta lactams work on?
Better on Gram positive - have bigger peptidoglycan area Can work on both Gram positive and Gram negative
377
What is the mechanism of action of beta lactam antibiotics?
Disrupt peptidoglycan production by: 1. Binding covalently and irreversibly to the penicillin-binding proteins (PBPs) particularly transpeptidase 2. Cell wall synthesis is disrupted and cell lysis occurs as peptidoglycan crosslinking can not occur → Active only against rapidly multiplying organisms.
378
Why do different classes of beta lactams differ in effectiveness?
Difference in the spectrum and activity of β-lactam antibiotics are due to their relative affinity for different PBPs
379
When should cephalosporins be used?
- Patients with penicillin allergy - Patients with meningitis as they can penetrate the head.
380
What are carbapenems?
Antibiotics designed to overcome the actions of beta lactamases and cephalosporinases Therefore these are the most broad specturm antibiotics and used as a last resort
381
Name some Carbapenems
Ertapenem Imipenem Meropenem
382
What is the problem with carbapenems?
They were the most broad spec antibiotic that could be used against anything however now there are carbapenem resistant bacteria
383
What are CREs?
Carbapenem resistant enterobacteriaceae: Pseudomonas aeruginosa Escherichia coli Klebsiella pneumoniae
384
What antibiotics would be used to treat: Cellulitis Strep throat Pneumonia
Gram positive bacteria so beta lactams: Cellulitis (S.aureus, Group A, C, G strep) - Flucloxacillin Strep throat (Group A,C, G strep) - PO penicillin V + IV Benzylpenicillin S.pneumonia - PO Amoxicillin + IV Benzylpenicillin
385
Give examples of some Glycopeptides
Vancomycin Teicoplanin
386
What is the route of administration for glycopeptides?
IV only
387
When do we use glycopeptides?
Only work on Gram positive bacteria: Used in MRSA Those with penicillin allergy
388
What types of antibiotics inhibit nucleic acid synthesis?
Rifampicin Metronidazole Fluoroquinolones
389
What does Rifampicin target?
RNA polymerase
390
What do fluoroquinolones target?
DNA gyrase and DNA topoisomerase IV
391
Give an example of a fluoroquinolone?
Ciprofloxacin (restricted antibiotic)
392
When do we use fluoroquinolones?
Gram negative > Gram positive: Penicillin allergy UTIs Intra-abdominal infections
393
What types of antibiotics will inhibit protein synthesis? Give an example for each
Aminoglycosides - Gentamicin (30s) Tetracyclines - Doxycycline (30s) Lincosamides - Clindamycin (50S) Macrolides - Clarithromycin/ Erythromycin (50s) Chloramphenicol
394
What is the route of administration of Aminoglycosides?
IV only
395
When do we use aminoglycosides?
Gram negative and Staph UTIs Infective Endocarditis
396
What is the route of administration of Tetracyclines?
PO only
397
When do we use tetracyclines?
Broad specturm but mainly gram positive (S.aureus and Streps) Cellulitis (if penicillin allergy) Pneumonia
398
What is the route of administration for lincosamides?
IV and PO
399
When do we use Lincosamides?
Gram Positive (S.aureus, Beta haemolytic strep and anaerobes) Cellulitis Necrotising Fasciitis
400
What is the route of administration of Macrolides?
IV and PO
401
When do we use Macrolides?
Gram positive (S.aureus, Beta haemolytic strep, atypical pneumonia) Severe pneumonia Penicillin allergy
402
What types of antibiotics inhibit folate synthesis?
Sulphonamides Trimethoprim
403
When do we use Trimethoprim?
Broad spectrum but mainly used for Gram negative UTIs
404
What questions should be asked before prescribing antibiotics?
1. How does it work? 2. What kind of bacteria will it cover? 3. Does it need to be IV or PO? 4. Does my patient have an infection caused by those bacteria? 5. Could there be resistance? 6. Are there any reasons why the patient couldn't have antibiotics?
405
What antibiotics do we commonly use to treat UTIs?
Nitrofurantoin First line for UTI and it only works in the lower respiratory tract Trimethoprim
406
What can be done to prevent patient to patient transmission of infection?
- Isolation - Antimicrobial stewardship - promoting and monitoring judicious use of antimicrobials to preserve their future effectiveness
407
What can be done to prevent environment to patient transmission of infection?
- Design (e.g. ventilation) - Cleaning - Patient isolation
408
What can be done to prevent staff to patient transmission of infection?
- Handwashing - Barrier precaution (e.g. gloves, gowns, etc.) - Isolation
409
Is handwashing or alcohol gel more effective at preventing Norovirus and C.diff?
Handwashing
410
What are endogenous infections?
Infections caused by the patients own flora
411
What common procedures often cause endogenous infections?
Surgery Catheterisation Cannulisation
412
When is someone who has chicken pox most infectious?
1-2 days before the onset of symptoms until all blisters have crusted over
413
What is the incubation period for chicken pox?
1-3 weeks
414
When can chickenpox infection be serious?
- Immunocompromised patients - Patients who have had transplants - Adults - Pregnant people - Smokers - Infants
415
What does the chicken pox rash look like?
- Erythematous macule which becomes an erythematous papule - Ends in a crust
416
What is the distribution of the chicken pox rash?
- Grows in warm areas of the body - Around neck and axillae
417
How should you collect a sample for diagnosis of chicken pox?
- Do not wipe the skin with alcohol swab - Pop lesion with a sterile needle - Absorb vesicle contents onto swab - Replace swab in casette and send for VZV/HSV PCR
418
What are some complications associated with VZV infection?
Dehydration Haemorrhagic change cerebellar ataxia Encephalitis Varicella pneumonia Skin and soft tissue infections
419
Describe the process of dormancy for the VZV virus?
- The virus travels along the sensory neurone axon until it reaches the dorsal root or cerebral ganglion - Here it lies dormant until reactivation - Shingles appear across single dermatomes for this reason - only 1 neurone is activated
420
What can cause reactivation of VZV?
Age Loss of immune response
421
What is post herpetic neuralgia and where is the most common body part for this to occur following reactivation of VZV?
After the shingles infection, the nerve endings are inflamed and causes painful stimulus The thorax
422
What are some red flags for shingles?
- 'Weird' dermatomes (where you wouldn't expect to find shingles rash) - Dissemination of the rash - Haemorrhagic changes - All suggest immunocompromised
423
What is the treatment for VZV infection?
Acyclovir
424
What is the distribution of an enterovirus rash?
Hand Foot Mouth
425
What care should be given to pregnant people with Hand, Foot and Mouth infection?
Not a danger to the foetus Supportive care - hydration and manage fever
426
What are some complications associated with Hand foot and Mouth infetion?
Cardiomyopathy Encephalitis Join inflammation (sternomastoid joint)
427
What is the hallmark of a parovirus infection?
Slapped cheeks Flushed cheeks with a reticular pattern
428
What are the complications of a parovirus infection?
Joint aches and pains - may last weeks Prevent RBC maturation - anaemia
429
Why is parovirus infection a problem in pregnancy?
Lack of ability to produce mature RBCs can make the foetus non-viable Foetus has to receive blood via the umbilicus
430
What is the distribution of HSV I and II?
HSV I - Mouth (Vermillion border, border of mucosa of lips and epithelium of skin) HSV II - Genitals
431
What has caused the distribution of HSV I and HSV II to become less defined?
Oral sex
432
Why is HSV infection a concern in pregnancy?
Can cause HSV encephalitis in the foetus
433
What is used to treat HSV?
Acyclovir
434
Describe a measles rash
Confluent morbidiform Sparing on pressure points
435
What are the symptoms of measles?
- Cough - Coryza - Diarrhoea - Conjunctivitis
436
Where does Macrolides, Cloramphenicol and Clindamycin act?
ACts on the 50S subunit of the ribosome to inhibt protein synthesis
437
Where do Tertracyclines and aminoglycosides act?
Act on the 30S subunit of bacterial ribosomes to inhibit protein synthesis
438
Where does Metronidazole and Nitrofurantoin act?
Damages DNA
439
Where do Quinolones act?
DNA topoisomers
440
Where does Rifampicin act?
RNA polymerase
441
Where do Penicillins, Cephalosporins and Carbapenems act?
Inhibit peptidoglycan cross linking
442
Where do Glycopeptides (vancomycin) act?
Inhibit peptidoglycan Synthesis
443
Where do Trimethoprim and Sulfonamides act?
Folic acid synthesis
444
What are some symptoms of Schistosomiasis?
Haematuria Bladder calcifications
445
What are the gram positive cocci?
Staphylococcus Streptococcus Enterococcus
446
What are the Gram positive rods and how do you remember them?
Corney Mikes Lister of Basic Cars: Corneybacteria Mycobacteria Listeria Bacillus Nocardia
447
What are the Gram positive anaerobes and how do you remember them?
CLAP: Clostridium Lactobacillus Actinomyces Propionbacterium
448
What are the major gram negative bacteria?
Neisseria meningitidis Neisseria gonorrhoea Haemophilia influenza E.coli Klebsiella Pseudomonas aeruginosa Morazella catarrhalis
449
What is an atypical bacteria?
A bacteria that cannot be cultured in the normal way or detected using a gram stain.
450
What are the atypical bacteria often implicated in?
Pneumonia
451
How do you remember the atypical penumonia
Legions of Psittaci MCQs Legionella pneumophilia a Chlamydia psittaci Mycoplasma pneumoniae Chlamydophila pneumoniae Q fever (coxiella)
452
What antibiotics can be used to treat MRSA?
Doxycycline Clindamycin Vancomycin Teicoplanin Linezolid
453
What are ESBLs usually susceptible to?
Carbapenems: meropenem imipenem
454
What species of bacteria are ESBLs usually?
E.coli Klebsiella often cause UTIs
455
When treating with antibiotics, what is the escalating process?
Start with Amoxicillin - covers streptococcus, listeria and enterococcus Swtich to co-amoxiclav - additionally covers staphylococcus, haemophilus and e.coli Switch to Tazocin to cover pseudomonas Switch to meropenem to cover ESBLs Add teicoplanin/vancomycin to cover MRSA Add clarithromycin or doxycycline to cover atypical bacteria
456
What is the most common cause of UTIs?
Escherichia coli
457
What is the most common cause of cellulitis?
Staphylococcus aureus
458
What is the most common cause of tonsilitis?
Streptococcus pyogenes
459
What is the most common cause of otitis media?
Streptococcus pneumoniae
460
What bacteria can amoxicillin be used against?
Gram positive
461
What bacteria can co-amoxiclav be used against?
Gram positive Gram negative Anaerobic
462
What type of bacteria is clarithromycin effective against?
Gram positive Atypical
463
What type of bacteria is gentamycin effective against?
Gram negative
464
What type of bacteria is ciprofloxacin effective against?
Gram negative atypical
465
What type of bacteria is metronidazole effective against?
Anaerobic bacteria
466
What type of bateria is doxycycline effective against?
Gram positive Gram negative Anaerobic Atypical
467
What type of bacteria is vancomycin effective against?
Gram positive
468
What is the first line option for treating cellulitis?
Flucloxacillin
469
What is the first lie option for treating UTIs?
Nitrofurantoin Trimethoprim
470
What is the first line treatment for treating chest infections?
Amoxicillin
471
What is the first line treatment for treating tonsilitis?
Phenoxymethylpenicillin
472
What is the primary function of the polysaccharide capsule?
Protection; prevents MAC or opsonisation molecules attacking.
473
What is the name for a hospital acquired disease
Nosocomial infection
474
What is a nosocomial infection?
An infection that originates within a hospital
475
Name the 3 conditions caused by salmonellosis.
1. Gastroenteritis. 2. Enteric fever. 3. Bacteraemia.
476
Why is v.cholerae so dangerous?
You're losing huge amounts of water which can result in hypovolemic shock and severe dehydration, this can lead to death.
477
Why is v.cholerae not killed if you have a fever?
It grows at 18 - 42°C.
478
Name 3 common fungal infections.
1. Nappy rash. 2. Tinea pedis. 3. Onychomycosis (fungal nail infection).
479
Name a drug that is good for treating onychomycosis.
Terbinafine - it reaches poorly perfused sites e.g. nails.
480
Antifungal treatments: how do azoles work?
They affect the ergosterol synthetic pathway.
481
Give 4 disadvantages of azoles.
1. High first pass metabolism, bioavailability = 45%. 2. ADR's, can cause hepatitis. 3. Drug interactions due to CYP450. 4. Resistance can develop e.g. in candida.
482
What is candida?
A yeast. It grows in warm, moist areas and has high levels of β-D-Glucan.
483
Where in the body would you find normal flora (commensals)?
1. Mouth. 2. Skin. 3. Vagina. 4. Urethra. 5. Large intestine.
484
Which Lancefield groups are associated with tonsilitis and skin infection? Give an example of a bacteria in the groups
A , C and G. A - S.pyogenes
485
Which Lancefield groups are associated with neonatal sepsis and meningitis? Give an example of a bacteria in the groups
B - S.agalactiae
486
Which group of streptococci can cause infective endocarditis?
Alpha haemolytic streptococci. Streptococci viridans - S.sanguinis, S.oralis
487
Why are there different clinical manifestations of malaria?
The difference in clinical manifestation can be due to variation in the plasmodia life cycle. The plasmodia life cycle has stages in the human and the mosquito.
488
What are the stages of the plasmodia life cycle in the human called?
Exo-erythrocytic and endo-erythrocytic stages.
489
What genetic conditions can give immunity to malaria?
Someone with sickle cell anaemia or thalassaemias.
490
Which HPV viral gene product controls viral gene expression?
E2.
491
Which HPV viral gene products inhibit p53 and Rb?
E6 and E7.
492
How does HIV attach onto a host cell?
GP160 binds to CD4 receptors and also CCR5 co-receptors.
493
Name 4 enzymes involved in HIV replication.
1. Reverse transcriptase. 2. Integrase. 3. RNA polymerase. 4. Proteases.
494
How many genes are encoded in the HIV genome?
9
495
What does Pol encode in the HIV genome?
Enzymes e.g. reverse transcriptase, integrase etc.
496
Why might macrophages also be infected by HIV?
Macrophages also have CD4 and CCR5 receptors.
497
Name 4 'sanctuary sites' for HIV.
1. Genital tract. 2. GI tract. 3. CNS. 4. Bone marrow.
498
What antibiotic might be used for the treatment of bacterial pharyngitis: 'strep throat'?
Phenoxymethylpenicillin. (Penicillin V)
499
What is the management/treatment of glandular fever?
Supportive therapy and advise the patient to avoid contact sport for 6 weeks in order to avoid splenic rupture.
500
Give some signs and symptoms of infective mononucleosis (glandular fever).
1. Reddening, swelling and white patches on the tonsils. 2. Swollen lymph nodes. 3. Spleen enlargement. 4. Chills, fever. 5. Cough. 6. Sore throat. 7. Fatigue, malaise, loss of appetite, headache.
501
Name 5 groups of people who are at high risk of HIV infection.
1. Homosexual men. 2. Heterosexual women. 3. Sex workers. 4. IV drug users. 5. Truck drivers.
502
Name 4 diseases that haemophilus influenzae can cause.
1. Meningitis. 2. Otitis media. 3. Pharyngitis. 4. Exacerbations of COPD.
503
Name 5 diseases that are notifiable.
1. Anthrax. 2. Cholera. 3. Rabies. 4. Smallpox. 5. Yellow fever. 6. Acute encephalitis. 7. Botulism. 8. Enteric fever. 9. Leprosy. 10. Malaria.
504
Name 6 vaccine preventable diseases that are notifiable.
1. Diptheria. 2. Measles. 3. Mumps. 4. Rubella. 5. Tetanus. 6. Whooping cough.
505
A patient has profuse vomiting after eating contaminated rice. What bacteria is responsible?
Bacillus cereus.
506
Name a bacteria that can cause ascending cholangitis.
Klebsiella pneumoniae.
507
What is the first line antibiotic for s.pyogenes?
IV benzylpenicillin.
508
What is the first line treatment for meningitis?
Cephalosporins - IV Cefotaxime.
509
What is the treatment for malaria?
Chloroquine.
510
What growth medium can be used to culture mycobacteria?
Lowenstein Jensen medium.
511
What organism can cause neonatal sepsis?
Group B streptococci.
512
Give examples of penicillin Antibiotics
Amoxicillin Flucloxacillin Benzylpenicillin Phenoxymethylpenicillin (Penicillin V)
513
Give examples of Cephalosporins Antibiotics
Cephalexin Cefotaxime Ceftriaxone
514
What type of bacteria would cell wall synthesis inhibitors be good against and why?
Gram positive bacteria because they have thicker cells walls for protection. Inability to synthesise their cell wall would make them vulnerable.
515
Give examples of macrolide antibiotics?
Clarithromycin Erythromycin
516
Give examples of tetracycline antibiotics
Doxycycline
517
Give examples of aminoglycoside antibiotics?
Gentamicin Streptomycin
518
What are the different classes of nucleic acid synthesis inhibitor antibiotics?
Folate synthesis inhibitors DNA Gyrase inhibitors RNA polymerase inhibitors DNA Strand breakers
519
What drugs inhibit folate acid synthesis?
Trimethoprim Sulphonamides Sulphamethoxazole
520
Why should you not give a pregnant women trimethoprim?
Because it will inhibit folate acid synthesis which is required for neural tube closure and therefore could cause the child to have spina bifida or anencephaly
521
What is Co-trimoxazole?
Combination therapy of: Trimethoprim + Sulphamethoxazole
522
What condition should you think of with fever and recent travel?
MALARIA Specifically in Africa, south America, south east Asia
523
What is Empirical Therapy?
Treating for a condition without knowing the specifics?
524
How do chest infections often present?
Cough Sputum production SOB Fever Lethargy Crackles on the chest
525
What are the common causes of chest infections?
Streptococcus pneumoniae (50%) Haemophilus influenzae (20%) Pseudomonas - in patients with CF or bronchiectasis Staph aureus - in patients with CF
526
What are the causes of Atypical pneumonia?
Atypical bacteria Legionella Chlamydia Psittaci Mycoplasma pneumoniae Chlamydydophila pneumoniae Q fever (coxiella)
527
What is the antibiotic of choice to treat chest infections? What are some alternatives that can be used?
Amoxicillin Erythromycin/Clarithromycin Doxycycline
528
What antibiotics would be used to treat atypical bacterial pneumonia?
Macrolides - clarithromycin Quinolones - Levofloxacin Tetracyclines - Doxycycline
529
Who are more affected by UTIs?
Women due to their urethra being much shorter and therefore it is easier for the bacteria to get into the bladder
530
What is a UTI?
Infection involving the bladder causing cystitis and this can also spread up to the kidneys causing pyelonephritis.
531
What is the main source of bacteria to cause a UTI?
Normal intestinal bacteria contaminate the urethral opening via faeces Usually E.coli
532
How may a UTI Present?
Dysuria (pain, stinging or burning when passing urine) Suprapubic pain or discomfort Frequency Urgency Incontinence Confusion is commonly the only symptom in older more frail patients
533
How may pyelonephritis present?
Fever is a more prominent feature than lower urinary tract infections. Loin, suprapubic or back pain. This may be bilateral or unilateral. Looking and feeling generally unwell Vomiting Loss of appetite Haematuria Renal angle tenderness on examination
534
What are the main causes of UTIs?
E.coli (most common) Klebsiella Enterococcus Pseudomonas S. saprophyticus Candida albicans
535
What are the antibiotics of choice for UTIs?
Trimethoprim Nitrofurantoin
536
When would Nitrofurantoin be avoided?
Third trimester as it is linked with haemolytic anaemia of the newborn
537
When would Trimethoprim be avoided?
Generally safe in pregnancy but avoided in the first trimester as it can affect folic acid metabolism and synthesis.
538
What is Cellulitis?
An infection of the skin and soft tissues underneath.
539
What is the presentation of cellulitis?
Erythema Warm/hot to touch Tense Thickened Oedematous Bullae (fluid filled blisters) Golden yellow crust - indicative of S. aureus infection
540
What are the most common causes of cellulitis?
Staphylococcus aureus Group A strep - S. pyogenes Group C strep - S. dysgalactiae
541
What is the antibiotic of choice to treat cellulitis? What are some alternatives that could be used?
Choice treatment: Flucloxacillin. Clarithromycin Clindamycin Co-amoxiclav
542
What is the most common cause of ENT infections?
Viral infections Tend to resolve without treatment over 1-3 weeks
543
What is the most common cause of bacterial tonsillitis?
Group A strep - S. pyogenes
544
What is the likely cause of otitis media, sinusitis and tonsilitis if they are not caused by Group A strep?
Streptococcus pneumoniae
545
How do you determine if tonsilitis is caused by a bacterial infection?
Via Centor Criteria A score of 3 or more gives a 40-60% probability of bacterial tonsilitis?
546
What is the Centor Criteria?
Bacterial tonsilitis indicated in a score of >3: Fever > 38 degree Celsius Tonsillar exudates Absence of cough Tender anterior cervical lymph nodes (lymphadenopathy)
547
What is the first line treatment for bacterial tonsilitis? What are some alternatives for broader spectrum?
Phenoxymethylpenicillin (Penicillin V) Co-amoxiclav Clarithromycin Doxycycline
548
What is otitis media?
It is difficult to distinguish between bacterial and viral otitis media. It presents with ear pain. Examination will reveal a bulging red tympanic membrane. If the ear drum perforates there can be discharge from the ear.
549
What is the first line treatment for Otitis media? What are some alternatives?
Amoxicillin Clarithromycin Erythromycin
550
What is the second line treatment for Otitis media if the patient is not responding to amoxicillin within 2 days?
Co-amoxiclav
551
What is the first line treatment for Sinusitis? What are the alternatives What is the second line treatment?
Penicillin V Alternatives are : Clarithromycin Erythromycin Doxycycline Second line is co-amoxiclav
552
What are some common causes of Intra-abdominal infections?
Anaerobes - Bacteriodes and clostridium E.coli Klebsiella Enterococcus Streptococcus
553
What are some common treatment regimes for intra abdominal infections?
Co-amoxiclav alone Amoxicillin plus gentamicin plus metronidazole Ciprofloxacin plus metronidazole (penicillin allergy) Vancomycin plus gentamicin plus metronidazole (penicillin allergy)
554
What is influenza?
The influenza virus is an RNA virus. There are three types: A, B and C, of which A and B are the most common. Type A has different H and N subtypes
555
Give some examples of Type A influenza subtypes?
H1N1 - Swine flu H5N1 - Avian flu
556
Who can receive the flu vaccine free on the NHS?
Aged 65 Young children Pregnant women Chronic health conditions such as asthma, COPD, heart failure and diabetes Healthcare workers and carers
557
What is the Presentation of viral influenza?
Fever Coryzal symptoms Lethargy and fatigue Anorexia (loss of appetite) Muscle and joint aches Headache Dry cough Sore throat
558
How is viral influenza diagnosed?
Viral nasal and throat swabs PCR
559
What are the treatment options of influenza in a patient at risk of flu complications?
Oseltamivir Zanamivir
560
What are some complications of influenza?
Otitis media, sinusitis and bronchitis Viral pneumonia Secondary bacteria pneumonia Worsening of chronic health conditions such as COPD and heart failure Febrile convulsions (young children) Encephalitis
561
What is the difference between: Acute gastritis Enteritis Gastroenteritis?
Acute gastritis is inflammation of the stomach and presents with nausea and vomiting. Enteritis is inflammation of the intestines and presents with diarrhoea. Gastroenteritis is inflammation all the way from the stomach to the intestines and presents with nausea, vomiting and diarrhoea.
562
What is the most common cause of gastroenteritis?
Viral infection
563
What viruses commonly cause gastroenteritis?
Rotavirus Norovirus Adenovirus is a less common cause and presents with a more subacute diarrhoea
564
What should be avoided if E.coli caused gastroenteritis is present?
Treatment with antibiotics as this may cause HUS
565
What is the most common cause of bacterial gastroenteritis?
Campylobacter jejuni
566
What are some symptoms of gastroenteritis?
Abdominal cramps Diarrhoea often with blood Nausea and Vomiting Fever
567
What are some bacterial causes of gastroenteritis?
E.coli Campylobacter jejuni Shigella Salmonella Bacillus Cereus - From reheated rice Yersinia Staphylococcus aureus Giardiasis
568
What are some potential complications of gastroenteritis?
Lactose intolerance Irritable bowel syndrome Reactive arthritis Guillain–Barré syndrome
569
What are the different methods of HIV Testing?
Antibody blood test Test for P24 antigen presence PCR testing for HIV RNA
570
What is used to monitor HIV?
CD4 T cell count (500-1200 cells/mm3 is normal range)
571
What type of bacteria is Group D streptococcus?
Enterococcus
572
What bacteria is it likely to be if you have a Gram positive bacteria in chains that gives a positive result on MacConkney Agar?
Enterococcus: Gram positive cocci Commonly found in the GI tract and will lactose ferment.
573
Give an example of an anti-pseudomonas penicillin?
Piperacillin + Tazobactam = Tazocin
574
Give an example of a monobactam
Aztreonam
575
What classes of antibiotics are bacteriocidal?
Glycopeptides Beta Lactams Fluoroquinolones Aminoglycosides
576
What classes of antibiotics are bacteriostatic?
Folate acid inhibitors (trimethoprim, sulphathiazole) Macrolides Lincosamides Chloramphenicol Linezolid Tetracyclines
577
What classes of antibiotics are bacteriostatic?
Folate acid inhibitors (trimethoprim, sulphathiazole) Macrolides Lincosamides Chloramphenicol Linezolid Tetracyclines
578
What Antibiotics would be useful against Gram positive bacteria?
Amoxicillin Co-Amoxiclav Clarithromycin Clindamycin Doxycycline Vancomycin
579
What Antibiotics would be useful against Gram Negative Bacteria?
Co-Amoxiclav Gentamycin Ciprofloxacin Doxycline
580
What Antibiotics would be useful against Anaerobic Bacteria?
Co-amoxiclav Clindamycin Metronidazole Doxycycline
581
What Antibiotics would be useful against Atypical Bacteria?
Clarithromycin Ciprofloxacin Doxycycline
582
How would you treat Clostridium Difficile?
Metronidazole PO Vancomycin