Phase 2 - Microbiology (ICS)

Question 1

Define pathogen

Answer 1

Organism that causes or is capable of causing disease

Question 2

Define commensal

Answer 2

Organism which colonises the host but causes no disease in normal circumstances - e.g. bacteria from throat can cause pneumonia in lungs

Question 3

Define opportunist pathogen

Answer 3

Microbe that only causes disease if host defences are compromised

Question 4

Define virulence/pathogenicity

Answer 4

The degree to which a given organism is pathogenic

Question 5

Define asymptomatic carriage

Answer 5

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

Question 6

Resolving power of naked eye

Answer 6

100μm

Question 7

Resolving power of light microscope

Answer 7

0.2μm

Question 8

Typical size of protazoa like entamoeba histolytica

Answer 8

~30μm

Question 9

Common size of spirochetes like borrellia recurrentis

Answer 9

~15μm

Question 10

Common size for bacilli like e. coli

Answer 10

~2-3μm

Question 11

Common size of cocci

Answer 11

~1μm

Question 12

Which is the biggest virus we learn of

Answer 12

Rotavirus

Question 13

What is the typical size of viruses

Answer 13

All smaller than 1μm

Bigger viruses ~0.3-0.8μm
Smaller virus <0.1μm

Question 14

What is the smallest virus we learn of

Answer 14

poliovirus

Question 15

What is unique about the nature of Chlamydia trachomatis

Answer 15

It is a bacteria but it is an obligate intracellular organism - it’s smaller than rotavirus

Rickettsia and Coxiella are also obligate intracellular bacteria

Question 16

Define serovar/serotype

Answer 16

a distinct variation within a species of bacteria/viruses/among immune cells of different individuals

Question 17

Which areas are open to bacterial colonisation

Answer 17

Mucosal surfaces

Bacteria can also get into many organs and cause inflammation

Question 18

What do the colours of the gram stain signify

Answer 18

Purple - gram positive
Pink/red - gram negative

purPle - Positive; piNk - Negative

Question 19

Basic shapes of bacteria

Answer 19

Coccus (round berry-like)
diplococcus (2 cocci)
streptococcus (chain of cocci)
staphylococcus (cluster of cocci)

Bacillus (rod)
Chain of rods
Vibrio (curved rod)
Spirochete (spiral rod)
Filamentous/branching bacteria

Question 20

Typical structures that a bacterium is composed of

Answer 20

Chromosome of circular double ctranded DNA (free in cytoplasm)
Inner membrane
Outer membrane
Pili/fimbriae
Cell wall

Some bacteria also have
- a capsule made from polysaccheride
- flagella
- plasmids, which can be transferred from bacterium to bacterium

Question 21

On which bacteria are capsules more common and why

Answer 21

On bacteria which get into blood/lungs

It helps protect them against the immune system

Question 22

What is the purpose of pili/fimbriae

Answer 22

Recepting/sensing the environment

Question 23

Which stain is commonly used for mycobacteria; what colour does it stain?

Answer 23

Ziehl-Neesen stain - stains red

Question 24

How does the ziehl-neelsen stain only stain non-gram bacteria? What is the term used for this kind of bacteria?

Answer 24

There is a stage in the Ziehl-Neelsen stain where the bacteria are bathed in alcohol/acid. Regular gram bacteria are decolourised at this stage but certain organisms like mycobacteria resist the acid.

These are called acid/alcohol fast bacteria (AFB or AAFB)

Question 25

Describe the cell envelope of a gram positive bacterium

Answer 25

Thin cytoplasmic membrane Thick layer of peptidoglycan with lipoteichoic acid strands within it Potentially a capsule

Question 26

Describe from inside to out the cell envelope of a gram negative bacterium

Answer 26

Cytoplasmic membrane: - Thin inner membrane - Very thin layer of peptidoglycan - (piller-like) Lipoproteins within periplasmic space - Thin outermembrane Lipopolysaccerides (ENDOTOXIN) - composed of: - Lipid A - O antigen - Terminal sugars potentially a capsule

Question 27

What is the peptidoglycan in bacteria

Answer 27

Crosslinked sugers and amino acids

Question 28

What causes the difference in staining between gram positive and negative bacteria?

Answer 28

Gram positive bacteria are able to resist decolouration (usually a mix of ethanol and acetone) due to their thick peptidoglycan layers Gram negative have a thin peptidoglycan layer so the stain is easily lost and they have to be counterstained (with safranin or basic fuchsin stain)

Question 29

What is a spore

Answer 29

Small oval or spherical structures with thick walls which are very resistant to high temperatures, radiation, desiccation and chemical agents. They are involved in reproduction and are used by certain bacteria to defend themselves. They can last for a long time in the environment

Question 30

What environment can bacteria survive in?

Answer 30

Temperature: <-800C to + 80C pH: <4 - 9 Water/desiccation: 2 hours - 3 months Light: could be killed by UV

Question 31

What environment can spores survive in

Answer 31

Temperature: <-800C to 1200C pH: <4-9 Water/desiccation: >50 years

Question 32

Growth rate of bacteria (give doubling time)

Answer 32

Common bacteria like E. coli or S. aureus: - In a broth or solid media: 20-30 min Mycobacterium tuberculosis in broth or media: - 24 hours Mycobacterium leprae in broth or media: - 2 weeks

Question 33

What is typically done now to test for mycobacteria in a culture

Answer 33

Grow too slowly for regular agar plate techniques ao using nucleic acid boosting techniques/PCR can be useful

Question 34

Types of bacterial toxins

Answer 34

ENDOTOXIN Component of the outer membrane of GRAM NEGATIVE bacteria, eg lipopolysaccharides EXOTOXIN Secreted proteins of Gram positive and Gram negative bacteria

Question 35

What is an example of a condition caused by bacterial exotoxins

Answer 35

Tetanus - causes simultaneous, prolonged, severe muscle contraction

Question 36

Differences between Endo- and Exotoxins (bacterial)

Answer 36

Exotoxins are composed of protein, endotoxins are composed of lipopolysacherride. Exotoxins have specific action while endotoxins are non-specific exotoxins are labile in heat, endotoxins remain stable exotoxins have strong antigenicity, endotoxins have weak antigenicity exotoxins are produced by both gram positive and gram negative; endotoxins are only found on gram negative (LPS) exotoxins can be converted to toxoid; endotoxins cannot

Question 37

How many chromosomes do bacteria normally contain

Answer 37

1 typically 2-4 x10^3 kb (kilobase - 1kb= 1000 bases)

Question 38

How many RNA polymerases do bacteria have

Answer 38

1

Question 39

What type of ribosomes do bacteria contain

Answer 39

30s/50s

Question 40

What does much of bacterial antibiotic resistance result from

Answer 40

Point mutations. Commonly: - base substitution - deletion - insertion

Question 41

How many bases typically in a plasmid

Answer 41

10-60 kb

Question 42

Name some sections commonly found in a plasmid

Answer 42

- Transfer promotion genes - plasmid maintenance genes - antibiotic/virulence determinant genes

Question 43

How are plasmids typically transferred between bacteria

Answer 43

Bacterial conjugation

Question 44

How can gene transfer occur in bacteria

Answer 44

- Transformation (gain from environment) eg via plasmid - Transduction eg via bacteriophage - Conjugation eg via sex pilus

Question 45

Where does most bacterial variation come from

Answer 45

Gene transfer - lateral transfer of genes

Question 46

Name the main obligate intracellular bacteria

Answer 46

Genus Rickettsia: - R. rickettsii - R. prowazekii - R. conorii - etc. Genus Chlamydia: - C. trachomatis - C. psittaci - C. pneumoniae Genus Coxiella: - C. burnetii

Question 47

Which notable illness is caused by the Rickettsia genus of bacteria

Answer 47

Rickettsia rickettsii causes: - scrub typhus/rocky mountain spotted fever - transferred via tick

Question 48

Which notable illnesses are caused by the Chlamydia genus

Answer 48

Chlamydia trachomatis can cause: - the STI - trachoma (eye infection) Chlamydia psittaci causes: - bird related pneumonia (can get from kissing pet parrots) Chlamydia pneumoniae: - associated with respiratory tract infections

Question 49

Name the bacteria that may be cultured on artificial media AND has NO cell wall

Answer 49

Mollicutes: - Mycoplasma pneumoniae (atypical pneumonia) - M. hominis (STIs and infertility) - Ureaplasma urealyticum

Question 50

Name the bacteria that may be cultures on artificial media AND has a cell wall AND grow as filaments

Answer 50

Genus ACTINOMYCES e.g. A. israelii Genus NOCARDIA e.g. N. asteroides Genus STREPTOMYCES (important source of antibiotics)

Question 51

Name the bacteria that may be cultures on artificial media AND has a cell wall AND grow as single cells AND are cocci AND gram negative

Answer 51

Anaerobic: Genus VEILLONELLA Aerobic: Genus NEISSERIA - N. meningitidis - N. gonorrhoeae

Question 52

What diseases are caused by the genus Neisseria

Answer 52

N. meningitidis causes: - meningitis in late teens/early twenties N. gonorrhoeae causes: - gonorrhoea (2nd most common bacterial STI) - has increased bacterial resistance

Question 53

Name the bacteria that may be cultures on artificial media AND has a cell wall AND grow as single cells AND are cocci AND gram positive

Answer 53

Anaerobic: - PEPTSTREPTOCOCCUS - ENTEROCOCCUS (E. faecalis) Aerobic: - STAPHYLOCOCCUS - STREPTOCOCCUS

Question 54

How can Staphylococcus be further divided up

Answer 54

Coagulase positive: - S. aureus (- S. intermedius) Coagulase negative: - S. epidermidis (- all other staph species)

Question 55

How can Streptococcus be further divided up

Answer 55

Alpha-haemolytic: - Viridans streptococcus - S. pneumoniae - S. sanguis - S. oralis etc. Beta-haemolytic: - S. pyogenes - S. agalactiae etc. Non-haemolytic: - S. bovis

Question 56

What do different haemolytic reactions look like

Answer 56

Alpha-haemolytic partially lyses blood (via production of hydrogen peroxide) so makes the bacterial colonies look green Beta-haemolytic fully lyses haem (via production of 2 pore-forming toxins) so turns blood agar clear Non-haemolytic can't lyse blood (also known as gamma-haemolysis)

Question 57

What is the Lancefield classification? Give names of relevent bacteria.

Answer 57

It classifies bacteria from group A to group G based on which antibody they have - S. pyogenes is Lancfield group A - S. agalactiae is Lancefield group B - Enterococcus faecalis (a different genus, NOT a strep) is Lancefield group D

Question 58

Diseases caused by staph

Answer 58

S. aureus - associated with skin infections; also sometimes endocarditis, particularly after dental surgery S. epidermis is oppertunistic, normally lives on skin but can cause infection if the human is compromised (e.g. due to catheter, plasters etc.)

Question 59

What diseases are caused by strep

Answer 59

S.pyogenes: - associated with pus, - causes scarlet fever - strep throat S. pneumonia causes: - common pneumonia - meningitis in older people Alpha-haemolytic strep - esp. viridans - associated with infective endocarditis

Question 60

Name the bacteria that may be cultured on artificial media AND has a cell wall AND grow as single cells AND are bacilli AND acid fast

Answer 60

MYCOBACTERIA: - M. tuberculosis (TB) - M. leprae (leprosy) - M. avium-intracellulare - M. ulcerans - M. kansasii - etc

Question 61

Name the bacteria that may be cultured on artificial media AND has a cell wall AND grow as single cells AND are bacilli AND gram positive

Answer 61

Anaerobic: - CLOSTRIDIUM * C. tetani (tetanus) * C. difficile (diarrhea) * C.perfringens * C. botulinum etc. - PROPIONIBACTERIUM * P. acnes Aerobic: - CORYNEBACTERIUM * C. diphtheriae etc - LISTERIA * L. monocytogenes etc - BACILLUS B. anthracis (Anthrax) B. cereus (food poisoning) etc

Question 62

Name the bacteria that may be cultured on artificial media AND has a cell wall AND grow as single cells AND are bacilli AND gram negative

Answer 62

Anaerobic: - BACTEROIDES * B. fragilis Aerobic: - 'Coliforms' (gut bacteria - non-spore forming) - 'Pseudomonads' (belonging to pseudomonas genus) - 'Vibrio' (curved rod) - 'Parvobacteria' (small, fastidious, non-spore forming coccobacilli)

Question 63

Name the bacteria that may be cultured on artificial media AND has a cell wall AND grow as single cells AND are bacilli AND gram negative AND are coliforms

Answer 63

ESCHERICHIA - e.g. E. coli KLEBSIELLA SALMONELLA - e.g. S. typhi SHIGELLA - e.g. S. sonnei CITROBACTER PROTEUS YERSINIA - e.g. Yersinia pestis etc

Question 64

Name the bacteria that may be cultured on artificial media AND has a cell wall AND grow as single cells AND are bacilli AND gram negative AND are Pseudomonads

Answer 64

PSEUDOMONAS - e.g. P. aeruginosa

Question 65

Name the bacteria that may be cultured on artificial media AND has a cell wall AND grow as single cells AND are bacilli AND gram negative AND are vibrio bacteria

Answer 65

VIBRIO - e.g. V. cholerae CAMPYLOBACTER - e.g. C. jejuni HELICOBACTER

Question 66

Name the bacteria that may be cultured on artificial media AND has a cell wall AND grow as single cells AND are bacilli AND gram negative AND are parvobacteria

Answer 66

HAEMOPHILUS - eg H. influenzae BRUCELLA BORDETELLA - e.g. B. pertusiss PASTEURELLA

Question 67

Name the bacteria that may be cultured on artificial media AND has a cell wall AND grow as single cells AND are spirochaetes

Answer 67

LEPTOSPIRA - e.g. L. icterohaemorrhagiae (Leptospirosis) TREPONEMA - e.g. T. pallidum (syphilis) BORRELIA - B. burghdorferi (lyme disease) - B. recurrentis etc

Question 68

Which antigenic groups of strep are Beta-haemolytic?

Answer 68

A, B, C, G

Question 69

How do you differentiate between viridans strep and S. pneumoniae?

Answer 69

Optochin test - Viridans strep is resistant to optochin; S. pneumonia is sensitive to optochin - On agar culture - optochin sensitivity looks like an area around the optochin disk that is clear of bacteria

Question 70

How do you differentiate between S. aureus and other staphylococcus

Answer 70

Coagulase/DNAse test - S. aureus is coagulase positive (also s. intermedius) - rest are negative

Question 71

What is a go-to antibiotic for staph infections

Answer 71

Flucloxacillin

Question 72

How many species of staph are there

Answer 72

at least 40

Question 73

What is coagulase? Why might this be produced?

Answer 73

Enzyme produced by bacteria that clots blood plasma - Fibrin clot formation around bacteria may protect from phagocytosis

Question 74

Where is the normal habitat of staph

Answer 74

nose and skin

Question 75

Are coagulase +ve or -ve staph more likely to cause problems

Answer 75

Coagulase +ve Coagulase -ve species (e.g. S. epidermidis) only important as opportunistic infections

Question 76

How is staph aureus spread

Answer 76

Aerosol and touch - some people are carriers/shedders

Question 77

What are S. aureus' virulence factors

Answer 77

Pore-forming toxins (in some strains) - α - haemolysin (low levels: apoptosis, high levels: mass necrosis) - Panton-Valentine Leucocidin ‘PVL’ (causes hemorrhagic pneumonia) Proteases - Exfoliatin (exotoxin - scalded skin syndrome) Toxic Shock Syndrome toxin (super antigen) - (stimulates cytokine release) Protein A - (surface protein which binds antibodies in wrong orientation)

Question 78

What is MRSA?

Answer 78

Methicillin (aka flucloxacillin) Resistant S. aureus - resistant to major antibiotics - break open beta-lactam ring of certain antibiotics - resitant to gentamicin, erythromycitetracycline

Question 79

Types of S. aureus infections

Answer 79

Pyogenic: - wound infections - causes: * abscesses * Impetigo * Septicaemia * Osteomyelitis * Pneumonia * Endocarditis Toxin mediated: - Scalded skin syndrome - Toxic shock syndrome - Food poisoning

Question 80

Name the main coagulase -ve staph species

Answer 80

- S. epiderimidis - S. saprophyticus

Question 81

Characteristics of S. epidermidis

Answer 81

- Oppertunistic infections * common in immunocompromised and people with prostheses - Main virulence factor - ability to form persistant biofilms (clusters of bacteria that are attached to a surface and/or to each other and embedded in a self-produced matrix)

Question 82

Characterictisics of S. saprophyticus

Answer 82

Causes acute cystitis (UTI) - commonly comes from skin contact in sexual intercourse Virulence factors: - haemagglutinin for adhesion - urease

Question 83

Is S. pyogenes aerobic or anaerobic?

Answer 83

It's facultatively anaerobic (can grow anaerobically or aerobically)

Question 84

Is S. pyogenes penicillic sensitive?

Answer 84

Yes

Question 85

Where is s. pyogenes most likely to infect?

Answer 85

Throat, skin, post partum infections

Question 86

What kind of infections are s. agalactiae associated with

Answer 86

Neonatal infections - passed from mother to child

Question 87

How are Lancefield groups tested? Describe the procedure.

Answer 87

Lancefield microbead agglutination test: - Antiserum (solution of antibodies) made that recognise each specific group - The antiserum is tagged to tiny plastic beads - These are added to a suspension of bacteria - If the bacterial antigen is complementary to the antiserum, they bind together and cause the beads to clump together - this is visible to the naked eye

Question 88

Virulence factors of S. pyogenes

Answer 88

Exported factors: - Enzymes * Streptokinase (important) ** breaks down clots * Hyaluronidase ** spreading * C5a peptidase ** reduces chemotaxis - Toxins * Streptolysins O&S (Important) ** binds cholesterol * Erythrogenic toxin (Importnat) ** Streptococcal pyrogenic toxin e.g. SPeA – exaggerated response ** Can lead to scarlet fever in children Surface factors: - Capsule - hyaluronic acid - M protein – surface protein (Important) (encourages complement degradation) * can cause scarlet fever in children

Question 89

Infections caused by S. pyogenes

Answer 89

Respiratory - Tonsillitis & pharyngitis (most common) - Otitis media Skin and Soft tissue - Wound infections - Impetigo - cellulitis - puerperal fever Scarlet fever - SPeA and M type Complications - rheumatic fever - glomerulonephritis

Question 90

Characteristic appearances of S. pneumonia in culture/tests

Answer 90

- “draughtsman” colonies (depressed central part with raised edges) - α- haemolytic - Gram positive cocci in pairs - Optochin sensitive

Question 91

Where is S. pneumonia often found (non-pathogenically)

Answer 91

Found as a commensal in oro-pharynx of 30% of population

Question 92

What does S. pneumoniae cause pathogenically

Answer 92

Pneumonia Otitis medis (middle ear infection) Sinusitis Meningitis

Question 93

What factors predispose to S. pneumoniae infection

Answer 93

- Impaired mucus trapping (e.g. viral infection) - Hypogammaglobulinaemia (problems making antibodies) - Asplenia (absence of spleen) - HIV

Question 94

S. pneumonia virulence factors

Answer 94

Capsule - polysaccharide (84 types), antiphagocytic Inflammatory wall constituents - teichoic acid (choline) - peptidoglycan Cytotoxin - pneumolysin (pore-forming)

Question 95

Which vaccines are there for S. pneumoniae infection

Answer 95

- polysaccharide vaccine ‘PPV’ - contains 23 types of pollysaccheride antigens from s. pneumoniae capsule - conjugate vaccine ‘PCV’ - contains 13 types of pollysaccheride antigens from s. pneumoniae capsule

Question 96

Who are S. pneumoniae vaccines given to and why

Answer 96

Only at risk people over 2 y/o The immune response to polysaccheride antigens is poor in the very young

Question 97

Who is at risk for S. pneumoniae infection

Answer 97

People with: - sickle cell disease, - asplenia, - renal disease, - immunodeficiency, - diabetes - chronic liver disease

Question 98

How does pneumolysin form pore

Answer 98

Subunits assemble into a ring structure on host cell surface thus forming a pore in the membrane

Question 99

Characteristics of Viridans group strep

Answer 99

α- haemolytic (or non-haemolytic) Optochin resistant

Question 100

What diseases can Viridans group strp cause

Answer 100

- Some cause dental caries & abscesses - typically live in mouth - Important in infective endocarditits (difficult to diagnose and treat) - Cause deep organ abscesses (e.g. brain, liver)

Question 101

Which strep species are typically associated with infective endocarditis? What is a typically presentation of this?

Answer 101

- S. sanguinis - S. oralis Very typical for people to get endocarditis after having dental surgery - they get into the blood from the mouth

Question 102

Most virulent group of Viridans group strep

Answer 102

'milleri group' S.intermedius, S.anginosus, S.constellatus

Question 103

Main aerobic Gram positive bacilli

Answer 103

- Listeria monocytogenes - Bacillus anthracis - Corunebacterium diphtheriae

Question 104

What does listeria monocytogenes cause?

Answer 104

causes listeriosis (starts as type of food poisoning - grows in moist areas) - usually self-limiting - can cause issues in immunocompromised people and pregnant women

Question 105

What does bacillus anthracis cause?

Answer 105

Anthrax - associated with cattle - spore forming so can be around for a long time 3 syndromes depending on route of acquisition: - Cutaneous - blister with black centre ('eschar') - Inhalation - respiratory sepsis - Ingestion - severe gasteroenteritis

Question 106

What does corynebacterium diphtheria cause

Answer 106

Diphtheria - infectin of pharynx * thick greyish pseudo membrane on tonsils can be a characteristic of it - involves infection of immune cells - involves metachromatic granules

Question 107

Main anaerobic gram positive bacilli

Answer 107

All main are types of CLOSTRIDIA - C. tetani - C. botulinum - C. difficile

Question 108

What does C. tetani cause? Associated symptoms and characteristics.

Answer 108

Tetanus - muscle contractions and stiffness progressing from head to body (neck stiffness, sore throat, difficulty opening mouth) - rictus grin - Get from infected wounds - Toxin inhibits GABA

Question 109

What does C. botulinum cause?

Answer 109

Botulism - paralysis spreading from head to body (from Botulinum toxin) - from contaminated food or infected wounds

Question 110

What does C. difficile cause?

Answer 110

Antibiotic associated diarrhea (as it kills off good bacteria and leaves C. difficile able to colonise more of the gut) - pseudomembranous colitis (destroys coloon)

Question 111

What are the components of LPS

Answer 111

- Lipid A - the toxic portion that is anchored in the outer leaflet of outer membrane - Core (C) antigen (AKA core oligosaccheride) - short chain of sugars, some are unique to LPS - Somatic (O) antigen (O-polysaccheride) - highly antigenic repeating chain of oligosaccherides

Question 112

Why do mycobacteria or mycoplasmas not stain with Gram stain? Are they considered gram positive or negative?

Answer 112

Mycobacteria outer lipid bilayer is composed of Mycolic acids Mycoplasmas don't have peptidoglycan - They are phylogenetically considered Gram positive

Question 113

The two types of virulence factors/pathogenicity determinants

Answer 113

Colonisation factors Toxins ('effectors')

Question 114

Name colonisation factors

Answer 114

Adhesins, invasins, nutrient acquisition, defence against the host

Question 115

sdfk

Question 116

What are toxins/’effectors’ released by gram bacteria?

Answer 116

- Usually secreted proteins that cause damage and subversion - In gram neg bacteria the protein secretion system spans both layers on the cell membrane - proteins are translocated from inside cytoplasm and secreted

Question 117

Which bacteria are within the Phylum proteobacteria

Answer 117

Enterobacteriaceae or Enterobacteria FAMILY (contains Shigella, salmonella, escherichia etc.) Vibrio (e.g. vibrio cholerae) Pseudomonans Haemophilus (e.g. H influenza) Legionella (e.g. Legionella pneumophila) Bordetella (e.g. bordetella pertussis) Neisseria Campylobacter Helicobacter (e.g. Helicobacter pylori)

Question 118

Characteristics of Enterobacteria

Answer 118

Rods Most are motile (have peritrichous flagella - flagella over their entire surface, like around the perimeter) Some species colonise the gut (commensals and pathogenic) Facultatively anaerobic

Question 119

Name main members of enterobacteria?

Answer 119

Shigella Escherichia (esp E. coli) Salmonella (e.g. S. enterica) Proteus (e.g. P. mirabilis) Klebsiella (e.g. K. pneumoniae) Less relevent according to lecturer: Serratia (e.g. S. marcenescens) Yersinia pestis Enterobacter spp.

Question 120

Which main enterobacteria are lactose use positive?

Answer 120

E. coli Klebsiella pneumoniae

Question 121

Which main enterobacteria are motile

Answer 121

E. coli Salmonella enterica Serratia marcensens (is this important??) Yersinia pestis at 25 degrees C (NOT motile at 37 degrees so NON-MOTILE inside humans) Proteus mirabilis

Question 122

Which main enterobacteria are NOT motile?

Answer 122

Shigella flexneri Klebsiella pneumoniae Yersinia pestis at 37 degrees C

Question 123

How do you test Lactose phenotype?

Answer 123

On MacConkey agar Selective for gram-negative bacteria (contains bile salts and crystal violet) Contains indicator so Lactose metabolising positive organism colonies turn red

Question 124

Which antigen is associated with flagella

Answer 124

H antigen

Question 125

How do you discriminate between similar bacteria like Salmonella and Shigella

Answer 125

Serology (in this case, no H (flagella) antigen pressent for Shigella)

Question 126

What is serotyping

Answer 126

Differentiating between specieses/strains by identifying cell surface antigens

Question 127

What is a serovar

Answer 127

Antigenically distinct varients of a single species

Question 128

What are the 3 main antigenic determinants for serotyping in gram negative bacteria

Answer 128

K antigen (exopolysaccheride 'capsulel') H antigen (flagella) O (somatic) antigen (LPS)

Question 129

What is Escherichia coli normally

Answer 129

Commensal gram -ve bacteria - most abundant facultative anaerobe in gut (10^7-10^8/g faeces) Has peritrichous flagella

Question 130

Principal infections caused by pathogenic E. coli

Answer 130

(i) Wound infections (typically post-surgical) (ii) UTIs (cystitis; 75-80% of female UTIs - faecal source or sexual activity; * catheterisation - most common type of nosocomial (originating in hospital) infection) (iii) Gastroenteritis (iv) Travellers’ diarrhoea (v) Bacteraemia (can be asymptomatic - sometimes leading to sepsis syndrome) (vi) Meningitis (infants) - rare in UK

Question 131

What are the species' of Shigella

Answer 131

S. dysenteriae, S. flexneri, S. boydii, S. sonnei

Question 132

What does shigella cause

Answer 132

Shigellosis: severe bloody diarrhoea (bacillary dysentery) - S. dysenteriae causes most severe form. BUT - S. sonnei most prevalent in developed world.

Question 133

Where is Shigella infection often found

Answer 133

Endemic in developing countries where sanitation is poor – mainly in children.

Question 134

Symptoms of shigellosis

Answer 134

Frequent passage of stools (>30/day) Small volume, pus and blood, prostrating cramps, pain in straining, fever Usually self-limiting (in adults)

Question 135

Pathogenesis of Shigella infection

Answer 135

Acid-tolerant (low infective dose, ~10^2) Person-to-person, or contaminated water & food (fresh/raw vegetables used in salads) Entry through colonic M cells (antigen sampling cells - lie over lymphoid follicles and deliver antigens to underlying immune cells) Induced uptake Important virulaence factor: Shiga toxin

Question 136

Pathology of Shigella

Answer 136

- lands on M cell apical surface - gets taken to basolateral surface - phagocytosed by macrophage (but rmains unharmed) - Shigella induces apoptosis of macrophage - moves laterally, destroying tissue - Macrophages also release cytokines to attract polymorphoneuclear leukocytes to the site of in fection causing more tissue damage

Question 137

What are the 2 specieces of Salmonella

Answer 137

S. enterica (has >2 500 serovars, including Salmonella enterica serovar Typhi) S. bongori (rare - contact with reptiles)

Question 138

What does S. enterica cause

Answer 138

salmonellosis (usually from contaminated food/drink) 3 forms: 1. Gastroenteritis/enterocolitis 2. Enteric fever 3. Bacteraemia (bacteria in blood)

Question 139

Pathogenesis of salmonellosis

Answer 139

Ingestion of contaminated food/water - high I.D. (infective dose)(~10^6) (‘faecal-oral route’) → Invasion of gut epithelium (small intestine) → Transcytosed to basolateral membrane → Enters submucosal macrophages → Intracellular survival/replication In Serovars Enteritidis and Typhimurium: - intestinal secretion and inflammatoryresponse are LOCALISED - DO NOT produce toxins In serovar Typhi: - Infection is SYSTEMIC due to dissemination within macrophages (macrophages migrate to reticuloendothelial organs via lymph and blood) - produces TYPHOID TOXIN (has DNAse activity - a genotoxin)

Question 140

Gastroenteritis/enterocolitis - causes and characteristics

Answer 140

Caused by serovars Enteritidis and Typhimurium Frequent cause of food poisoning (milk, poultry meat & eggs) Second highest no. of food-related hospitalisations/deaths (UK) 6-36 hr incubation period, resolves (~7 days) Localised infection, only occasionally systemic

Question 141

Enteric fever - causes/characteristics

Answer 141

Typhoid/paratyphoid fever - caused by serovars Typhi and Paratyphi Linked to poor quality drinking water/poor sanitation Systemic disease ~20 million cases, ~200,000 deaths/year (globally)

Question 142

What causes Bacteraemia

Answer 142

Serovars Cholerasuis and Dublin - it is uncommon

Question 143

Steps of gastroenteritis pathogenesis

Answer 143

1. Bacterial-mediated endocytosis 2. Induction of interleukin-8 release → 3. Neutrophil recruitment and migration 4. Neutrophil-induced tissue injury → 5. Fluid and electrolyte loss → diarrhoea Inflammation/necrosis of gut mucosa

Question 144

Steps of enteric/typhoid fever pathogenesis

Answer 144

1. Bacterial-mediated endocytosis 2. Transcytosis to basolateral membrane 3. Survival in macrophage (MΦ) → systemic spread Initially, little damage to gut mucosa

Question 145

What % of people become carriers of S. enterica serovar Typhi

Answer 145

~10% are carriers for < or = 3 months (bacteria shed in faeces) ~ 1-4% become chronic carriers (at least a year or more)

Question 146

Notable characteristic of Proteus mirabilis

Answer 146

Can differentiate into an elongated hyperflagellated form → gives it surface motility (ability of ‘swarming’) over solid surface

Question 147

What does Proteus mirabilis cause

Answer 147

Catheter-associated UTIs (~30% of cases) - can ascend and cause pyelonephritis (kidney infection) Formation of bladder/kidney stones, can block catheter - does this by producing urease (increasing urine pH) which forms ammonia and leads to calcium phosphate precipitation

Question 148

Characteristics of Klebsiella pneumoniae

Answer 148

- environmental (it is an enterobacteria but more common in environment) - opportunistic, nosocomial infections (neonates, elderly, compromised) - colonisation of gastrointestinal tract (normal) and oropharynx (less frequently) is often benign Multi-drug resistant (resistant to carbapenems)

Question 149

What does Klebsiella pneumoniae cause

Answer 149

UTI, pneumonia (aspiration from oropharynx), surgical wound infections from gut, bacteraemia → sepsis (high mortality).

Question 150

Characteristics of Vibrio cholerae

Answer 150

- Facultative anaerobe - Normally from Saline environments: commensal to planktonic crustaceans such as copepods → ingestion by shellfish → contamination of drinking water due to flooding of coastal areas or poor sanitation (faecal contamination) - characteristic curved rod shape

Question 151

What does vibrio cholerae cause

Answer 151

Cholera: Most severe diarrhoeal disease Associated with LPS O1 serotype → epidemics (and occasionally O139 variant) Characterised by pandemics (7 recorded since 1817)

Question 152

History of Choleral pandemics

Answer 152

1P-6P, Indian subcontinent; 7P began in Sulawesi (1961) → SE Asia (1963) → Africa (1970) → Latin America (1991) → Caribbean (2010) 1.4-4.0 million cases/year, 20,000-140,000 associated deaths

Question 153

General pathology of Cholera (aquisition, incubation, consequence)

Answer 153

Faecal-oral route (not person-to-person) - high infective dose required (not acid resistant) (faecal contaminated water (poor sanitation) or undercooked shellfish from risk areas) ↓ Incubation, few hours to 5 days (V.c. multiplies in small intestine) ↓ Voluminous watery stools (‘secretory’ diarrhoea - rice water stool) Can lose 20 litres fluid/day plus electrolytes → dehydration/death (hypovolaemic shock) → 50-60% mortality if untreated No blood, pus or fever (i.e. not dysenteric) i.e. no invasion or damage to mucosa

Question 154

What can most cases of Cholera be treated by

Answer 154

Oral re-hydration therapy (ORT)

Question 155

What is the main virulence factor of V. cholerae

Answer 155

Cholera toxin

Question 156

Pathogenesis of Cholera (mechanism of cholera toxin)

Answer 156

CT binds to a glycolipid receptor on epithelial cell (B subunits) A subunit ADP-ribosylates G-protein (Gs) → locked in ‘ON’ state Uncontrolled cAMP production Protein kinase A activated Phosphorylates CFTR (cystic fibrosis transmembrane conductance regulator) anion transporter CFTR activity modified (loss of Cl- & Na+ into gut lumen) → massive loss of H2O

Question 157

Characteristics of Pseudomonas aeruginosa

Answer 157

Ubiquitous, free-living (in environment), motile (single polar flagellum), rod-shaped. Opportunistic (serious cause of nosocomial infections) Resistant to multiple antibiotics (& disinfectants) - very difficult to treat

Question 158

Infections caused by P. aeruginosa. Can it cause acute or chronic?

Answer 158

Acute infections: (i) Localised - burn/surgical wounds - UTI (catheters) - Keratitis (infection of cornea - requires some kind of scratch etc.) (ii) Systemic (bacteraemic → sepsis - hard to treat) - affects neutropenic patients - low white blood cell count (leukaemia, chemotherapy, AIDS) (iii) affects ICU patients (ventilator acquired pneumonia) - leading cause of nosocomial pneumonia Chronic infections: (i) In Cystic fibrosis (CF) patients Common denominator to all infections - compromised host defences

Question 159

What happens in cystic fibrosis (general overview)

Answer 159

Defective CFTR (chloride ion transporter)→ thick mucus produced in lungs. - Lungs prone to microbial infection

Question 160

Most problematic source of infection for CF patients

Answer 160

P. aeruginosa

Question 161

Types of P. aeruginosa

Answer 161

P. aeruginosa ‘wild-type’ (non-mucoid) P. aeruginosa ‘CF’ phenotype (mucoid) = mutants that secrete a thick coating of exopolysaccharide (i.e. hyper-produce capsule): provides additional protection against host defences in the lung

Question 162

What leads to the progressive lung damage following infection of CF lung by P. aeruginosa

Answer 162

Mainly due to effect of host immune system trying to clear infection

Question 163

Characteristics of Haemophilius influenzae

Answer 163

Exclusively human parasite (obligate/ no environmental reservoir): Nasopharyngeal carriage in 25-80% population (non-capsulate strains) - transient carriage of capsulate strains occurs in 5-10% (more dangerous as they are invasive - can move around body) Oppertunistic

Question 164

Who are particularly susceptible to H. influenzae infection

Answer 164

Young children and adult smokers

Question 165

What infections can Haemofilius influenza cause

Answer 165

- Meningitis* (age <5 yrs), 5-10% of adult cases ∙ Bronchopneumonia ∙ Epiglottitis*, sinusitis, otitis media ∙ Bacteraemia* (often associated with pharyngitis) ∙ Pneumonia in CF, COPD, HIV patients * infections caused by capsulate strains (invasive) – uncommon in healthy adults

Question 166

Diagnostic characteristics of H. influenxae

Answer 166

Fastidious - requires ‘factor X’ (haem) and ‘factor Y’ (NAD) - requires chocolate agar (lysed/oxidised blood) Non-motile

Question 167

Virulence determinants of H. influenzae

Answer 167

(i) Capsule - invasive strains are capsulate (‘encapsulated’) → can penetrate nasopharyngeal epithelium → resistance to phagocytosis and complement system - 6 different capsule serotypes (a-f) (type b strains are the main cause of meningitis) Commensals and upper respiratory tract pathogens are non-capsulate referred to as ‘non-typeable’ H. influenzae (NTHi) (ii) LPS (‘endotoxin’) → inflammation → complement resistance

Question 168

Which vaccine has reduced the cause of H. influenza caused meningitis

Answer 168

Hib vaccine (HH. influenza type b)

Question 169

What does Legionella pneumophila cause, source of acquisition and who does it usually affect

Answer 169

Legionnaires’ disease - severe inflammatory pneumonia (1-3% of all pneumonias) - 15-20% mortality Infection from man-made aquatic environments (air-conditioning cooling towers, shower heads, nebulisers, humidifiers etc.) - never person-to-person transmission - replicate within freshwater protozoa - can repliacte in alveolar macrophages too Affects immunocompromised (elderly, alcoholics, smokers etc.)

Question 170

What does Bordetella pertussis cause

Answer 170

Pertussis (whooping cough) Non-specific flu-like symptoms (~7 d), followed by paroxysmal coughing (https://www.youtube.com/watch?v=l5SHtdczSBc) (B. parapertussis causes mild pharyngitis)

Question 171

Characteristics of B. pertussis

Answer 171

Humans - only known reservoir (obligate human pathogen) Highly contagious (low I.D.) - aerosol transmission (- produces pertussis toxin and Adenylate cyclase-haemolysin toxin (CyaA)) Non-invasive

Question 172

Diagnostic characteristics of B. pertussis

Answer 172

Short (sometimes oval) rods (coccobacilli) Fastidious Gram negative

Question 173

Diagnostic characteristics of Neisseria

Answer 173

Non-flagellated diploccoci Fastidious Gram -ve

Question 174

Where can Nessieria be found in the environment

Answer 174

Humans are the only known reservoir

Question 175

Characteristics of N. meningitidis

Answer 175

Nasopharyngeal carriage in 5-10% population (asymptomatic) Rises to 20-90% during outbreaks Person-to-person (aerosol) transmission (universities, barracks, Haj)

Question 176

Pathogenesis of N. meningitidis

Answer 176

crosses nasopharyngeal epithelium and enters bloodstream → low level - bacteraemia (asymptomatic) or high level - septicaemia (sepsis - high mortality if not treated) → meningitis: invasion of the meninges - bacteria enter CSF of subarachnoid space after crossing blood-brain barrier (second most frequent cause of meningitis in young children)

Question 177

Virulence determinants of N. meningitidis

Answer 177

(i) Capsule is major virulence determinant (serogroup B - 90% cases) → anti-phagocytic (noncapsulated N.m. only found in nasopharynx - not pathogenic) (ii) LPS (membrane ‘blebs’) → cytokine cascade → sepsis

Question 178

What are non-blanching petechial pr purpuric rashes associated with

Answer 178

Meningococcal sepsis (capillary damage - bleeding - ecchymosis AKA bruising)

Question 179

What does N. gonorrhoeae cause

Answer 179

Gonorrhoea - second most common STD worldwide

Question 180

How is gonorrhoea transmitted

Answer 180

Person-to-person only

Question 181

How often can N. gonorrhoeae infection be asymptomatic

Answer 181

~10% men, ~50% women

Question 182

Characteristic infection presentation of gonorrhoea

Answer 182

Urethritis with additional infection of female genitalia. Serious complications in women - can lead to salpingitis (fallopian tubes) and/or PID (pelvic organs) if infection ascends. Proctitis, gingivitis, pharyngitis depending on sexual preference Can transmit as conjunctivits to newborns

Question 183

Are gonococci capsulated or not

Answer 183

They are non-capsulated

Question 184

Helicobacter pylori appearance

Answer 184

spiral shape, tuft of polar flagella

Question 185

Where are H. pylori found in the body

Answer 185

Discovered in gastric mucus (1982) which was previously thought to be sterile

Question 186

Incidence of H. pylori in global population

Answer 186

Present in ~50% global population, but only a fraction develop disease

Question 187

Which diseases are H. pylori associated

Answer 187

Major role in gastritis and peptic ulcer disease (80-90% of ulcers) Implicated in ~10% cases of gastric adenocarcinoma & mucosa-associated lymphoid tissue lymphoma (linked to production of VacA and CagA toxins)

Question 188

Name of main bacteria in Phylum bacteroidetes

Answer 188

Bacteroides

Question 189

Characteristics of Bacteroides

Answer 189

Non-motile rods Obligate anaerobes Commensal flora of colon (most abundant organism in gut - 30-40% of total) Opportunistic

Question 190

What amount per g of faeces is Bacteroides? Population ratio compared to E. coli?

Answer 190

>10^10/g faeces (outnumbers E. coli 20:1)

Question 191

What infections can infections can Bacteroides cause

Answer 191

Infection of tissue injury (surgery, perforated appendix or ulcer) → predominantly peritoneal cavity infections (peritonitis, intrabdominal abscesses are most common) can lead to bacteraemia Most frequent cause of banaerobic infections Often present in polymicrobial infections with enterobacteria - presence of facultative anaerobes depletes O2, allowing anaerobes such as Bacteroides to proliferate

Question 192

Which Bacteroides species is most commonly responsible for infections

Answer 192

B. fragilis (although it is only 0.5-1.0% of total commensal Bacteroides)

Question 193

Which genuses are in Phylum Chlamydiae

Answer 193

Chlamydia and Chlamydophila

Question 194

Characteristics of Chlamydia and Chlamydophila

Answer 194

Very small, non-motile. Obligate intracellular parasites. Many species within this group live asymptomatically as endosymbionts in amoebae, invertebrates and vertebrates. Cannot culture in bacteriological media - detect by serum Abs (antibodies - tho these could be due to previous infection so anleternate confirmatory test must also be done) or PCR (AKA NAA or NAAT)

Question 195

Life cycle of Chlamydia and Chlamydophila

Answer 195

2 developmental stages: (i) Elementary bodies (EBs) - rigid, extracellular form, ~0.3 μm, dormant infectious enter cell through endocytosis prevent phagosome-lysosome fusion ↓ differentiates into... (ii) Reticulate bodies (RBs) - fragile, intracellular form, ~1.0 μm, metabolically active replicative non-infectious acquire nutrients from host cell

Question 196

How many developmental stages in life cycle of Chlamydia/Chlamydophila

Answer 196

2 - Elementary body stage - Reticulate body stage

Question 197

Form/characteristics of Chlamydia/Chlamydophila Elementary bodies

Answer 197

Rigid, dormant extracellular form ~0.3 micrometers

Question 198

What occurs during the elementary body phase of Chlamydia/Chlamydophila life cyle

Answer 198

Infectious Enter cell throughendocytosis prevent phagosome-lysosome fusion (so it can't be destroyed by host defence of cell)

Question 199

What happens in reticulate body phase of Chlamydia/Chlamydophila life cycle

Answer 199

Non-infectious Replication Acquire nutrients from host cell

Question 200

Characteristic of Chlamydia/CHlamydophila reticulate body

Answer 200

fragile, metabolically active, intracellular form pleiomorphic ~1.0 micrometers

Question 201

Medically important members of genus Chlamydia

Answer 201

C. trachomatis (has 3 biovars): - trachoma biovar (serotypes A-C) - gentital tract biovar (serotypes D-K) - lympho granuloma venereum (LGV) biovar

Question 202

What disease does the Chlamydia trachomatis biovar trachoma cause

Answer 202

Trachoma → blindness (eye-to-eye transmission via hands, fomites (innanimate objects like mascara brushes) or flies) Largest cause of preventable blindness caused by infectius organisms Easily treated if caught early but often not recognised till later

Question 203

What does C. trachomatis biovar genital tract cause

Answer 203

Chlamydia STI - most common STD in UK - infects epithelial cells of mucous membranes of urethra (both sexes) and vagina - can ascend to uterus and ovaries (PID, infertility) - usually asymptomatic (i.e. 70-80% cases in women) Conjunctivitis (hand-to-eye transmission OR mother-to-child during delivery)

Question 204

What does the lympho granuloma venereum (LGV) biovar of Chlamydia trachomatis cause

Answer 204

LGV (an STD) - invasive urogenital/anorectal infection - endemic to the tropics, cases rising in Europe/North America

Question 205

Medically important members of Chlamydophila

Answer 205

C. pneumoniae C. psittaci

Question 206

What does C. pneumoniae cause

Answer 206

Resp tract infection (mild/’walking’ pneumonia) Causes ~10% community acquired pneumonias

Question 207

What does C. psittaci cause

Answer 207

Psittacosis (severe pneumonia) Mainly affects bird owners (zoonotic) Uncommon

Question 208

Spirochaete physical form

Answer 208

Long, slender, helical, highly flexible

Question 209

Characteristics of Spirochaetes

Answer 209

Most are free-living and non-pathogenic Pathogenic varieties difficult to culture Has a modified outer membrane (Treponema and Borrelia lack LPS, have a different glycolipid instead)

Question 210

Where is the spirochaete endoflagella located

Answer 210

Between peptidoglycan and outer membrane Periplasmic flagella Fixed at each end of bacterium and confers shape Overlap in centre of bacterium

Question 211

Characteristics of spirochaete endoflagella function

Answer 211

Propels in corkscrew motion Swims faster in high viscosity medium (i.e. normal environment of spirochaetes) ‘Hides’ antigenic flagellum

Question 212

What are the 3 medically important members of Spirochaetes

Answer 212

Borrelia burgdorferi Leptospira interrogans Treponema pallidum

Question 213

What does Borrelia burgdorferi cause

Answer 213

Lyme disease

Question 214

How is Lyme disease transmitted

Answer 214

Via ticks B.b. infects small mammels (e.g. rodents) Tick larvae feeding on the infected animal acquire B.b. Usually transmitted to humans by tick nymphs (adults easier to spot)

Question 215

Symptoms of Lyme disease

Answer 215

Bull’s eye rash Flu-like symptoms (fever, fatigue, headache) (neurological problems in 10-15% patients, joints → arthritis) Most symptoms arise as consequence of immune response

Question 216

How can lyme disease spread within the human body

Answer 216

dissemination via lymphatics/blood to other organs

Question 217

What does leptospira interrogans cause

Answer 217

Leptospirosis (zoonosis) - rare in UK Symptoms of leptospirosis: - Flu-like - Severe form (Weil’s disease) in 10-15% infected individuals * jaundice, acute renal and hepatic failure, pulmonary distress, haemorrhage

Question 218

How is leptospirosis acquired?

Answer 218

Contact of infected animal urine with mucous membrane or abraded skin

Question 219

What does treponema pallidum cause

Answer 219

Syphilis

Question 220

How many stages of syphilis (treponema pallidum infection)

Answer 220

3 Primary stage Secondary stage Tertiary stage

Question 221

What occurs in primary stage syphilis (treponema pallidum infection)

Answer 221

Localised genital infection (chancre) Defined as days-weeks post-infection (i.e it is in the primary stage if it is occuring within days/weeks of being infected)

Question 222

What occurs in secondary stage syphilis (treponema pallidum infection)

Answer 222

Systemic skin (rash), swollen lymph nodes, joint pains, muscle aches, headache, fever Occurs at 1-3 months post-infection Highly transmissible ~50% of cases are at secondary stage

Question 223

What occurs in tertiary stage syphilis (treponema pallidum infection)

Answer 223

‘Gummas’ (granulomas) in bone and soft tissue Cardiovascular syphilis (affects aorta) Neurosyphilis (affects brain and spinal cord) Occurs several years post-infection Non-infectious

Question 224

How can syphilis be treated

Answer 224

All stages can be treated with antibiotics but treatment is longer for tertiary stage syphilis and tertiary-related damage can’t be reverted

Question 225

Name mycobacteria of medical importance and their relevant medical condition

Answer 225

M. tuberculosis - tuberculosis M. leprae - Leprosy M. avium complex (MAC) - Disseminated infection in AIDS, chronic lung infection (oppertunistic - doesn’t usually affect humans) M. kansasii - Chronic lung infection (oppertunistic - doesn’t usually affect humans) M. ulcerans - Buruli ulcer (west africa/ australia - often affects kids - doesn’t usually kill but maims) Rapidly growing mycobacteria (AKA M. fortuitum complex) - Skin/soft tissue infections M. marinum - fish tank granuloma (asymptomatic in tropical fish - skin conditions in humans)

Question 226

Are most mycobacteria environmental or human organisms

Answer 226

Most are environmental TB evolved to infect humans and some other mammals like bovines

Question 227

How is leprosy (m. leprae) communicated

Answer 227

Through respiratory mediums Only infectious in early respiratory period

Question 228

What effect does leprosy have on humans

Answer 228

Skin hypopigmentation - some lesions present Neural lesion - loss of sensation and pain response

Question 229

What socioeconomic factor is leprosy associated with

Answer 229

poverty

Question 230

Stages of Buruli ulcer (m. ulcerans infection)

Answer 230

Nodule Small ulcer Large ulcer Bone destruction (causes deformation)

Question 231

What is severe Buruli ulcer associated with

Answer 231

Poverty - don’t have resources to seek medical help until sever, late stages It is treatable if found at an early stage

Question 232

Characteristics of TB

Answer 232

Infects people over a long period of time People put large amount of bodies resources into fighting off TB thus causing consumptive appearance Leading cause of death by infectious disease

Question 233

Mycobacteria physical appearance

Answer 233

Slightly curved, beaded bacilli

Question 234

What makes mycobacteria resistant to gram stain?

Answer 234

High lipid content with mycolic acid in cell walls

Question 235

Ziehl-Neelsen stain process

Answer 235

Red Carbol fuchsin added Washed with acid/alcohol (mycobacteria are acid fast so resistant to destaining) Add Methylene blue

Question 236

How many bacilli are needed for a diagnosis

Answer 236

10 000 bacilli per ml of sputum

Question 237

Characteristics of mycobacteria

Answer 237

Aerobic, non-spore forming, non-motile Cell wall has high molecular weight lipids

Question 238

Key components of mycobacteria cell wall

Answer 238

Mycolic acids Lipoarabinomannan

Question 239

How fast do mycobacteria grow

Answer 239

M. tuberculosis generation time is 15-20h vs. 1h for common bacterial pathogens - Have to wait at least 48 hours before you can declare no M. tuberculosis is growing in a culture - Slows down diagnosis

Question 240

What is generation time?

Answer 240

Time taken for bacterial population to double in number

Question 241

How is TB transmitted

Answer 241

aerosol transmission

Question 242

What occurs in primary TB?

Answer 242

Initial contact made by alveolar macrophages Bacilli taken in lymphatics to hilar lymph nodes

Question 243

What is latant TB

Answer 243

Where Primary infection is controlled but cell mediated immune response from T cells persits No clinical disease (as immune system is strong enough to keep bacilli trapped in granulomas) Cell mediated immune response to TB can still be detected via tuberculin skin test Can remain in the body in this form for decades

Question 244

What occurs in Pulmonary TB

Answer 244

Can be post-primary (immediately after primary infection) or after reactivation Granulomas form around bacilli that have settled in the apex of lungs * more air and less blood supply (fewer white blood cells) Necrosis occurs in granuloma/tubercles (looks kasiated - like cheese) resulting in abscess formation and caseous material coughed up May spread in lungs causing other lesions

Question 245

What are granulomas dependant on

Answer 245

A sufficient number of CD4 cells and TNF alpha being present

Question 246

What increases risk of TB becoming active

Answer 246

Immunosuppression Anti-TNF therapies (given for chronic inflammation)

Question 247

What is a primary complex in TB

Answer 247

Consists of granuloma, lymphatics and lymph nodes

Question 248

What issues can TB cause when it spreads beyond lungs

Answer 248

TB meningitis Miliary TB Pleural TB Bone and joint TB Genito-urinary TB

Question 249

How can TB be spread beyond lungs

Answer 249

Carried by macrophages which then move around body

Question 250

What does TB of spine cause?

Answer 250

Bent gibbus formation

Question 251

Immunological response to mycobacteria

Answer 251

Mycobacteria phagocytosed by macrophages and attempted to phagolysosome Mycobacteria have adapted to intracellular environment and aims to withstand phagolysosomal killing and escape to cytosol

Question 252

What does effective immunity to M. TB require

Answer 252

CD4 T-cells (this immune response is t cell and macrophage mediated) CD4 generate interferon gamma (IFN-y) - this helps activate intracellular killing by macrophages; and other cytokines like TNFa

Question 253

What does the granuloma consist of

Answer 253

Macrophages and Th1 lymphocytes capable of synthesysing IFN-y and other cytokines like TNF alpha

Question 254

What happens if TB granuloma works? What happens if it doesn’t work?

Answer 254

Mycobacteria shut down metabolically in order to survive - dormancy But if fails, e.g. in the lung, this can result in the formation of a cavity full of live mycobacteria and eventual disseminated disease (can lead to abcesses eventually)

Question 255

What needs to be done first when trying to culture mycobacteria

Answer 255

Decontamination to kill off other rapid growing bacteria (lipid coat protects mycobacteria)

Question 256

What methods can be used to culture mycobacteria

Answer 256

Solid cultures - Egg based Lowenstein Jensen - Agar based Middlebrook 7H11 - Take 2-8 weeks Liquid culture - Automated systems BACTEC - Mycobacterial growth indicator tube (MGIT). - Fluorometric detection in liquid media - Takes 1-3 weeks

Question 257

What allows more rapid diagnosis of mycobacteria

Answer 257

Nucleic acid detection (with PCR)(GeneXpert MTB/RIF cartridge based test)

Question 258

Name of Nucleic acid detection test used for mycobacteria

Answer 258

GeneXpert MTB/RIF cartridge based test (learn name, was highlighted by lecturer)

Question 259

What does the GeneXpert MTB/RIF cartridge based test do

Answer 259

Purifies and concentrates MTB, sonicates to release genomic material and then performs PCR Detects Rifampicin resistance using fluorescence

Question 260

How many bacilli/ml (minimum) can GeneXpert MTB/RIF cartridge based test for mycobacteria detect?

Answer 260

131 bacilli/ml

Question 261

How sensitive and specific is GeneXpert MTB/RIF cartridge based test for mycobacteria?

Answer 261

Sensitivity 88%, Specificity 98% (learn the sensitivity, it was highlighted by lecturer)

Question 262

Is M. TB fastidious?

Answer 262

yes

Question 263

When may nucleic acid detection of TB not pick up on TB

Answer 263

if TB is latent

Question 264

How can latent TB be recognised

Answer 264

Via tuberculin/Mantoux test Bit of TB protein is injected into skin (intradermal) If previously infected TB memory cells will be present so skin will become inflamed Similar test can be done with blood in solution

Question 265

What is the downside of tuberculin/Mantoux test

Answer 265

Can pick up on the person having had a TB vaccination (presence of antibodies doesn’t necessarily mean they were infected)

Question 266

How quickly is T cell response stimulated after exposure to M. TB

Answer 266

3-9 weeks

Question 267

Positive and negative effects of T cell response stimulation in TB

Answer 267

+ve effects; - macrophage killing of mycobacteria , - containment of infection, - formation of tissue granulomata. -ve effects; - hypersensitivity reactions with skin lesions, - eye lesions - swelling of joints

Question 268

Standard drug therapy for TB

Answer 268

isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (ETH) x 2 months followed by isoniazid and rifampicin for further 4 months

Question 269

Second line treatment for TB

Answer 269

Injectable agents (streptomycin, cycloserine, capreomycin) - Severe side effects, including liver damage

Question 270

How long does TB treatment take

Answer 270

4-9 months of combination therapy

Question 271

What are the resistance mechanisms of M. TB to drugs

Answer 271

Drug inactivation: - Mtb produces beta- lactamase Drug titration: - Target overproduction Alteration of drug target: - Missense mutations Altered cell envelope: - Increased permeability and drug efflux

Question 272

Multi-drug resistant TB: cause and characteristic

Answer 272

Resultant from inadequate TB therapy and failure to clear patients of bacteria XDR-TB: resistant to four commonly used TB drugs. 6% of all TB cases

Question 273

Treating XDR-TB

Answer 273

Lengthy and expensive BPaL regimen: - Bedaquiline - Pretomanid - Linezolid - All orally administered for 6 months BPaL can also fail with totally drug resistant TB - No known solution

Question 274

How do viruses cause disease

Answer 274

- Direct destruction of host cells - Modification of host cell - “Over-reactivity” of immune system - Damage through cell proliferation - Evasion of host defences

Question 275

What is the leading cause of death world wide

Answer 275

Lower resp tract infection (e.g. can be caused by Respiratory Syncytial Virus)

Question 276

Importance of viral infections in the UK

Answer 276

- Outbreaks (e.g. Influenza, Measles, Mumps, Norovirus) - Cancer (e.g. EBV and lymphoma, Hep B/C and hepatocellular carcinoma, HPV and cervical/anal cancer, HIV and many resulting infections) - Immunosuppressed patients (Reactivation of latent viruses) - Miscarriage and birth defects (e.g. CMV, VZV, HSV, Rubella) - Morbidity and mortality (Psychological and physical)

Question 277

Which viruses can lie latent and reactivate upon immunosuppression

Answer 277

All herpes class viruses: - EBV, - CMV, - human herpesvirus 6 (HHV6), - human herpesvirus 7 (HHV7), - JC virus (human polyomavirus 2), - BK virus (human polyomavirus 1

Question 278

Which viruses are herpes class

Answer 278

- Herpes simplex virus 1 - Herpes simplex virus 2 - Varicella-zoster virus - Cytomegalovirus - Epstein-Barr virus - Human Herpesvirus 6 (varients A and B) - Human Herpesvirus 7 - Kaposi’s sarcoma virus AKA human herpesvirus 8

Question 279

What is a virus?

Answer 279

An infectious, obligate intracellular parasite comprising genetic material (DNA or RNA) surrounded by a protein coat and/or a membrane All also have a receptor binding protein to “dock” to cells

Question 280

Range of sizes of human viruses

Answer 280

20 to 260nm in diameter Poxviruses are some of the biggest Parvovirus is the smallest

Question 281

Viruses vs Bacteria

Answer 281

- Bacteria have cell wall, viruses don’t - Bacteria have organelles, viruses don’t - Bacteria have DNA and RNA, viruses only have DNA or RNA - Viruses are always dependant on a host cell, bacteria are not - Bacteria are living organisms, viruses are typically considered not living

Question 282

Are DNA or RNA viruses typically hardier

Answer 282

DNA viruses

Question 283

What are virions

Answer 283

The complete, infective form of a virus outside a host cell consisting of genetic material (DNA or RNA) and a protein coat/capsid

Question 284

Different shapes of viruses

Answer 284

- Helical (spiral shaped genetic material) - Icosahedral (cubic? Looks like those regular 3D shapes they make with paper for maths class) - Complex (e.g. bacteriophage looks like a weird spider creature)

Question 285

Different types of viral external structure

Answer 285

- Non-enveloped (e.g. adenovirus, parvovirus) - Enveloped (e.g. Influenza, HIV)

Question 286

What would you examine when detecting a new virus

Answer 286

Genetic sequence

Question 287

Stages of viral replication

Answer 287

1. ATTACHMENT to specific receptor 2. CELL ENTRY 3. HOST CELL INTERACTION and REPLICATION 4. ASSEMBLY OF VIRION 5. RELEASE OF NEW VIRUS PARTICLES

Question 288

What does the attachment receptor of a virus dictate

Answer 288

Dictates the type of cells the virus can infect - E.g. gp120 receptor on HIV allows it to attach to CD4 cells with CCR5 or CXCR4 chemokine receptors as coreceptors

Question 289

What happens during cell entry by a virus

Answer 289

Virion is uncoated within the cell Only central viral “core” (nucleic acid and some associated proteins) is used for replication

Question 290

What happens during host cell interaction and replication of a virus

Answer 290

- Viral genome migrates to cell nucleus - Viral genome is transcribed to mRNA using host material (enzymes, amino acids, nucleotides) - Subverts host cell defence mechanism (as it is using own resources)

Question 291

What does translation of viral mRNA produce

Answer 291

- Structural proteins - Viral genome - Non-structural proteins e.g. enzymes

Question 292

Where can assembly of virion occur within host cell

Answer 292

- Nucleus (e.g. like herpes viruses) - Cytoplasm (e.g. like poliovirus) - At cell membrane (e.g. influenza virus)

Question 293

How can new virus particles be released from host cell?

Answer 293

- Particles can burst out causing cell death e.g. like rhinovirus - Particles can bud off/exocytose, taking some of cell membrane with it e.g. HIV, Influenza

Question 294

Example of direct destruction of host cells by a virus

Answer 294

Poliovirus - causes host cell lysis and death after viral replication period of 4 hours As polio affects neurons - this neuronal lysis/death leads to paralysis

Question 295

Example of virus causing disease by modification of host cell

Answer 295

Rotavirus - atrophies villi and flattens epithelial cells - Decreases small intestine SA - Nutrients including sugar not absorbed - Hyperosmotic state - Profuse diarrhoea

Question 296

Example of a virus causing disease via “over-reactivity” of immune system

Answer 296

Hep B - Causes hepatocytes to be attacked by cytotoxic T lymphocytes Results in: - Jaundice - Pale stool - Dark urine - RUQ (right upper quadrant abdominal) pain - Fever and malaise - Itching (from release of bile salts) When Hep B is chronic the sustained viral replication and hepatocyte destruction occurs at a lower level so has fewer clinical symptoms (also SARS-Cov-2)

Question 297

Example of virus causing damage through cell proliferation

Answer 297

HPV causes cervical cancer - After acquisition through direct contact there is partial viral replication and expression of some HPV proteins - Viral DNA is integrated into host chromosome - This leads to continuous expression of oncoproteins causing cellular DNA mutations - And so we get dysplasia and neoplasia

Question 298

Example of virus causing damage through evasion of host defences

Answer 298

At a cellular level: - Latency e.g. herpesviridae - Cell-cell spread e.g. measles, HIV At molecular level - Antigenic variability e.g. Influenza, HIV, rhinovirus - Prevention of host cell apoptosis e.g. herpesviridae - Downregulation of interferon and other intracellular host defence proteins (many viruses do this) - Interference with host cell antigen processing pathways e.g. herpesviridae, measles, HIV

Question 299

Where does each of the main herpes viruses lie dormant

Answer 299

- HSV 1 and 2 and VZV lie latent in Nerve root ganglion - EBV and HHV-8 (AKA Kaposi sarcoma virus) - Lymphoid cells - HHV-6, HHV-7, CMV - lie latent in Myeloid cells

Question 300

What are the advantages of direct cell-cell spread

Answer 300

- Avoids random release into environment - Increased speed of spread within tissues - Avoiding immune system

Question 301

What is antigenic variability

Answer 301

Ability to change surface antigens to evade host immune system Through mutations during replication

Question 302

How does prevention of host cell apoptosis by virus cause damage

Answer 302

Prevention of host cell apoptosis allows the virus to continue replicating within it, so more virus is produced and then released. It also has an essential role into how some viruses are oncogenic

Question 303

How does downregulation of interferon and other intracellular host defence proteins by viruses cause damage

Answer 303

- Normally interferon is synthesised and allows messaging to other cells to activate their antiviral state - When interferon synthesis is blocked, it leaves the neighbouring cells susceptible to infection

Question 304

How can viruses interfere with host cell antigen processing pathways

Answer 304

Can down regulate MHC class 1 so the viral antigen is not identified quickly by immune system

Question 305

Why can viruses vary in the range of clinical syndromes they cause

Answer 305

- They can infect different host cells and tissues - They have different methods of interaction with the host cell

Question 306

What symptoms can they cause: Herpes simplex virus vs JC virus

Answer 306

HSV Skin: - Orofacial herpes - Genital herpes - Herpetic whitlow - Erythema multiforme - Herpes gladiatorum Visceral: - Oesophagitis - Pneumonitis - Hepatitis CNS: - Meningitis - Encephalitis - Transverse myelitis Eye: - Conjunctivitis - Keratitis JC virus: CNS - Progressive multifocal leukoencephalopathy

Question 307

Which viruses can cause common cold

Answer 307

- Rhinovirus - Parainfluenza virus - Respiratory syncytial virus

Question 308

Which viruses can cause eye infections

Answer 308

- Herpes Simplex - Adenovirus - CMV

Question 309

Which viruses can cause Encephalitis/meningitis

Answer 309

- JC virus - Measles - LCM virus - Arbovirus - Rabies

Question 310

Which viruses can cause pharyngitis

Answer 310

- Adenovirus - EBV - CMV

Question 311

Which viruses can cause gastroenteritis

Answer 311

- Adenovirus - Rotavirus - Norovirus - Astrovirus - Coronavirus

Question 312

Which viruses can cause skin infections

Answer 312

- VZV - HHV-6 - Smallpox - Molluscum contagiosum - HPV - Parvovirus B19 - Rubella - Measles - Coxsackie A virus

Question 313

Which viruses cause sexually transmitted diseases

Answer 313

Herpes simplex type 2 HPV HIV

Question 314

Which viruses can cause gingivostomatitis

Answer 314

Herpes simplex type 1 Gingivostomatitis = Infection of mouth and gums that leads to swelling and sores

Question 315

Which viruses can cause pneumonia

Answer 315

Influenza virus type A and B Parainfluenza virus Resp syncytial virus Adenovirus SARS coronavirus

Question 316

Which viruses can cause Myelitis

Answer 316

Poliovirus (HTLV-I)

Question 317

Which viruses cause pancreatitis

Answer 317

Coxsackie B virus

Question 318

Which virus can cause cardiovascular infection

Answer 318

Coxsackie B virus

Question 319

What are the diagnostic tests for detecting viruses

Answer 319

- PCR (detects presence of genetic material and the initial size of viral load - doesn't work for novel viruses) - Serology (Checks for viral exposure. Is there immune memory to the virus) - Histology (any features of viral infection present?) - Viewing a viral culture through light microscopy (structure of infected cells visibly changes) - Limited clinical use* - Electron microscopy - Limited clinical use* * Too much time/effort, too expensive

Question 320

Key points about viruses

Answer 320

- Viruses are a COMMON AND SIGNIFICANT cause of human disease globally and nationally (in UK) - Viruses are very SMALL and consist of GENETIC MATERIAL surrounded by a PROTEIN COAT - A virus is COMPLETELY DEPENDANT on host cell machinery to replicate - Recognising how viruses cause disease allows us to: - Understand transmission and natural history - Know who is most at risk - Develop treatments and “preventative” drugs - Viruses vary wildly in range of clinical syndromes they can cause (infect diff cells/tissues AND diff methods of interaction with host)

Question 321

What does the Varicella Zoster Virus cause

Answer 321

Varicella “chickenpox” - primary infection Herpes zoster (HZ) “Shingles” - secondary reactivation * Very infectious

Question 322

What does a VZV particle consist of

Answer 322

- Double strand DNA genome - Nucleocapsid - Tegument (cluster of proteins lining space between envelope and neucleocapsid) - Lipid envelope - Glycoprotein spikes

Question 323

Infection timeline of VZV

Answer 323

- VZV enters body - Incubation period (1-3 weeks) - Rash - High infectivity period occurs 1-2 days before rash appears to when the blisters have crusted over

Question 324

When is chickenpox most infectious

Answer 324

1-2 days before rash appears to when the blisters have crusted over

Question 325

Where does VZV replicate in body

Answer 325

Nasopharynx - present in nasal secretions

Question 326

How can VZV be transmitted

Answer 326

- Nasal secretions e.g. sneezing - Contact with vesicular matter

Question 327

Epidemiology of chickenpox

Answer 327

- Common in childhood - Highly contagious, (90% in household hit rate) - Usually benign but can be serious in certain groups 90% of adults raised in the UK have had chickenpox

Question 328

Risk groups for chickenpox

Answer 328

- Immunocompromised and patients who have had transplants - Adults - Pregnant women - Smokers - Infants

Question 329

Socioeconomic issue of endemic/chronic illnesses

Answer 329

Lots of lost school days and sick days from work Decrease productivity

Question 330

Progressive stages of chickenpox blister

Answer 330

- Macule - red spot, not prominently raised - Papule - slight raised bump - Vesicle - small blisters - Pustule - pus-filled, white blisters - Crust - rougher, scabbing

Question 331

Distribution of chickenpox rash

Answer 331

- More central - rash forms in warmer areas so sparser on extremities - Lesions at different stages of progression can appear on body

Question 332

Characteristics of smallpox rash

Answer 332

- Centrifugal distribution - more appears on face and extremities (away from centre) - All lesions evolve at same time (so all at same stage of progression) - Deeper lesions, affecting deeper layers of skin - some have central umbilication (dip in middle

Question 333

What is something that is pathognomonic to chickenpox

Answer 333

Cropping - having lesions at different stages but in the same area of body

Question 334

Diagnosis of chickenpox

Answer 334

- Pop lesion with sterile needle - (DON’T wipe with alcohol swab first - can denature virus) - Absorb vesicle contents onto swab - Replace swab in cassette and send for VZV/HSV PCR

Question 335

Complications of chickenpox

Answer 335

- Dehydration - Haemorrhagic change to the rash - Cerebellar ataxia (common) - unsteady gait - Encephalitis - confused, diorientated, loss of motor function, possible sizure - Varicella pneumonia - Bacterial empyema (pockets of pus collected inside body cavity - esp pleural space) - Skin and soft tissue infection typically with group A strep - Bone and joint infections: deep sepsis-osteomyelitis/pyomyositis - Congenital (foetal) varicella syndrome RARE in children - MORE COMMON in adults

Question 336

What is the most common complication of chickenpox in adults

Answer 336

Chickenpox pneumonitis Affects 15% of healthy adults 30% risk in lung disease/smoker 30% mortality untreated 6% mortality even with treatment

Question 337

Treatment for Varicella pneumonitis

Answer 337

- Antiviral - Acyclovere (10mg per kg, 3 times a day - IV*) * doesn’t work well orally - Valacyclovere (valine sidechain) when getting better (can be taken orally)

Question 338

How common is foetal infection of VZV in pregnancy

Answer 338

10-15% ~2% develop FOETAL VARICELLA SYNDROME (FVS) when mother contracts chickenpox in FIRST HALF of pregnancy (v rare)

Question 339

Characteristics of foetal infection of chickenpox

Answer 339

- Usually transient (only lasts short amount of time) and asymptomatic - If any manifestations - usually shingles in first year of life

Question 340

Potentially severe defects that can occur as complications of FVS

Answer 340

- Cicatricial skin scarring (scarring from formation + contraction of fibrous tissue in wound) - Limb hypoplasia (poorly developed limbs) - Visceral/ocular lesions - Microcephaly (small head) and growth retardation

Question 341

How are serum samples collected

Answer 341

- Blood sample taken - Tube contains gel to separate cells from serum once centrifuged - Small sarstedt (name of brand) tubes kept for around 3 years (archive samples)

Question 342

When are initial serum samples taken in pregancy

Answer 342

~10-12 weeks pregnant

Question 343

Why are archived serum samples useful

Answer 343

Can compare archived serum sample when taking sample later to check for stuff

Question 344

How does shingles reactivate as a unilateral rash

Answer 344

- First - primary infection of widespread chickenpox - VZV goes dormant in dorsal root (or cerebral) ganglion - Localised reactivation - singles (only affects that dermatome unilaterally as virus can’t cross over midline to other side of spine)

Question 345

What type of viruses is dormancy and reactivation more common in

Answer 345

DNA viruses

Question 346

Characteristic onset of shingles

Answer 346

Most common in elderly Can go from no rash to horrible rash in day or so

Question 347

Pain relief for shingles rash

Answer 347

- Regular analgesia doesn’t work properly - Have to use drugs that dampen nerve tips (normally used for epilepsy) - E.g. Gabapentine

Question 348

Sites of shingles reactivation

Answer 348

- Thoracic region (50-70% of all cases) - Cervical, lumbar and sacral - less frequent - Ophthalmic (10-20%) - affecting ophthalmic division of trigeminal nerve - particularly problematic as shingles can affect every layer of eye + cause vision problems

Question 349

Long term complication of shingles (even after the infection is resolved)

Answer 349

Post-herpetic neuraligia - Nerve endings stay irritated for 2 years or so after the rash is gone

Question 350

What is the Hutchinson sign and what does it indicate

Answer 350

A lesion on the tip of the nose - Indicates the shingles probably has corneal involvement

Question 351

Complications/signs of shingles becoming complicated

Answer 351

- Dissemination - Haemorrhagic change - Shingles in peripheral dermatomes - means immune system isn’t controlling things well In Immunocompromised - can get SECONDARY infection (e.g. bacterial)

Question 352

Complications of herpes virus in people with atopic dermatitis/eczema

Answer 352

Eczema herpeticum - Rash looks like it’s never quite come under control - Seems like a combination of herpes virus and rapidly worsening eczema

Question 353

What do enteroviruses cause

Answer 353

Hand foot and mouth disease - Shed enteroviruses in stool

Question 354

What pathologies cause rash on palms and soles of feet

Answer 354

- Enteroviruses (hand, foot, mouth disese) - Secondary syphilis (bacterial) - Part of an immune response to drugs - toxic erythema (erythema is just like bruising)

Question 355

What does Parvovirus B19 target and basic method of action for how they do this

Answer 355

Immature red cells - They attach to P antigens displayed by immature red cells which prevents normal maturation

Question 356

Complications of parvovirus B19

Answer 356

Profound anaemia - blood cells not replaced as older cells die * Better prognosis in children Complications in pregnant women: - Hydrops fetalis - severe swelling in foetus

Question 357

Treatment for hydrops fetalis

Answer 357

Can give trans umbilical transfusion to increase chance of survival till birth - then supportive measures e.g. assited breathing, removal of excess fluid via needle - Intervention only works in early stages

Question 358

How do you test for hydrops fetalis

Answer 358

Middle cerebral artery dopplers (detects resistance of flow in foetal brain circulation)

Question 359

Characteristics of parvovirus B19 rash

Answer 359

- Reticular rash (net-like pattern) - Flares up in higher temperatures e.g. in hot bath

Question 360

What rash does HHV-6 cause

Answer 360

Roseola - larger, more spread-out patches of slightly raised, darker skin

Question 361

Characteristics of HSV rashes

Answer 361

- Vesicular rashes - Lesion on vermillion border of lip - common sight of herpes rash - Rashes below belt as well

Question 362

Typical locations of HSV1 and HSV2 rashes

Answer 362

- HSV1 - both above and below belt - HSV2 - typically only below belt

Question 363

Complications of HSV in immunosuppressed patients

Answer 363

Mucositis - Sore areas in mouth - mucosal epithelium is shed Bugs can target these shed areas - secondary infections E.g. candida plaques

Question 364

Name a common pox virus, especially in children

Answer 364

Moluscum contagiosum - CAN ALSO BE BE SEXUALLY TRANSMITED (in genital areas)

Question 365

How can moluscum contagiosum be treated

Answer 365

- Pop vesicle and remove white centre - However, if too rough, can cause further skin damage and it can come back

Question 366

Which part of moluscum contagiosum often reactivates in immunosuppressed people

Answer 366

Lesions around eyes

Question 367

Which age group is primary cytomegalovirus infection most common in

Answer 367

Teens and 20s

Question 368

Diagnostic appearance of Primary CMV

Answer 368

Macular rash Lymphadenopathy - Atypical lymphocytes (sticky, destructive, spread out)

Question 369

Complications of CMV reactivation

Answer 369

- Retinitis - pizza pan retina - sight threatening - CMV pneumonitis (most viral pneumonitis look very similar/same) - dangerous - Colitis with CMV on top

Question 370

Histological hallmark of CMV

Answer 370

Owl’s eye intranuclear inclusions - NORMALLY TREATED WITH PCR tho

Question 371

How is CMV treated

Answer 371

IV ganciclovir - Or Valganciclovir can be orally taken in less severe case (val is just valine group which allows oral consumption)

Question 372

What does measles cause

Answer 372

- Cough, coriza (runny nose), conjunctivitis, diarreah - Maculopapular rash (dry feel) - Salt grain-like lesions in mouth - Febrility - Otitis media (can cause hearing loss in severe cases) - Potential pneumonia - Potential encephalitis

Question 373

What do the local health protection unit control

Answer 373

Cough, coriza, conjunctivitis, diarreah, immune control

Question 374

How transmissible is measles

Answer 374

R0 = 16 (very high) 100 in unvaccinated population

Question 375

Characteristic skin presentation of Dengue shock syndrome

Answer 375

Significant bruises/swelling from internal bleeding

Question 376

Which gram +ve bacteria can cause cellulitis

Answer 376

S. aureus and Group A (pyogenes), C, G strep

Question 377

Which gram +ve bacteria can cause pharyngitis/strep throat

Answer 377

Group A, C, G strep

Question 378

Define protozoa

Answer 378

Single cell with nucleus - is eukaryotic >30, 000 specieses

Question 379

What are the 5 major groups of protozoa

Answer 379

Flagellate Amoeba Sporozoa Microsporidia Ciliate

Question 380

List main flagellate protozoa

Answer 380

- Trypanosoma brucei gambiense (African trypanosomiasis - sleeping sickness) - Trypanosoma brucei rhodesiense (African trypanosomiasis - sleeping sickness) - Trypanosoma cruzi (American Trypanosomiasis - Chagas Disease) - Leishmania spp. (Leishmaniasis) - Trichomonas vaginalis (Trichomoniasis - STI) - Giardia lamblia (Giardiasis)

Question 381

Which protozoa cause African trypanosomiasis?

Answer 381

- Trypanosoma brucei gambiense - Trypanosoma brucei rhodesiense (Batman puts you to sleep by stabbing with a needle in gambia or rhodes)

Question 382

Which organism transmits African trypanosomiasis

Answer 382

Tsetse fly (via bite)

Question 383

What does African trypanosomiasis cause

Answer 383

- Chancre - Flu like symptoms - CNS involvement (sleepy, confusion, personality change) - Coma and Death

Question 384

How is African Trypanosomiasis diagnosed

Answer 384

Via blood film or CSF

Question 385

Which protazoa causes American trypanosomiasis (Chagas disease)

Answer 385

Trypanosoma cruzi (Jesus got nailed to a cross - people felt ill)

Question 386

How is american trypanosomiasis spread

Answer 386

- Through contact with faeces of triatomine “kissing” bug (found around/in mud huts in South America) - Through blood - Vertically acquired - Eating contaminated food

Question 387

Symptoms of American Trypanosomiasis (Chagas disease)

Answer 387

Acute: - Flu like symptoms - Lymphadanopathy - (Romaña sign - swollen eyelid - if faeces rubbed into eye) - (Chaga means fester/disease in Portuguese) Chronic: - Cardiomyopathy (harder to pump - walls of heart: stretched, thickened or stiff) - Megaesophagus (oesophagus dilates and loses motility) - Megacolon (dilation)

Question 388

How is Chagas disease diagnosed

Answer 388

- By visualising trypomastigotes (the type of flagellate protozoa that causes Chagas) on blood film - OR amastigotes (the protozoa have no visible flagellum!) on biopsy (for CHRONIC) Remember as: they need flagella (masti) to move around if only temporary (i.e. acute) but Chagas requires maturity in life which causes you to keep most of your potential inside so trypomastigote not promastigote. When it is chronic the -mastigotes get comfortable and stop moving around (thus no VISIBLE flagella - promastigote)

Question 389

Important types of trypanosomatida

Answer 389

- Amastigote - no visible flagella (but potential for flagella still there) - Promastigote - anterior flagella (cell itself looks like cover of edamame beans/pea pod) with flagellum STICKING MOSTLY out of the cell - Trypomastigote - Still bean pod looking cell with anterior flagella but most of the flagellum is now INSIDE the cell but at the edge i.e ATTACHED PARALLELY TO CELL MEMBRANE

Question 390

Can Chagas disease be treated

Answer 390

Can be treated effectively if acute CANNOT effectively treat once chronic - can only provide supportive treatments e.g. pacemaker, antiarrhythmias etc.

Question 391

Which organisms cause Leishmaniasis

Answer 391

Leishmania! Spp. (means specieses - >20 affect humans) - protazoa (Lesion mania - in the sand)

Question 392

How is leishmaniasis spread?

Answer 392

Via bite of sand fly

Question 393

How is Leishmaniasis diagnosed

Answer 393

- Via biopsy (can see amastigotes) - Via serology combined with clinical signs - Can be diagnosed with PCR

Question 394

What are the 3 clinical pictures of Leishman

Answer 394

- Cutaneous - Mucocutaneous - Visceral (baso increasing severity from superficial to deep - also gets more virulent with increasing severity)

Question 395

What does cutaneous Leishmaniasis cause

Answer 395

Most common Ulcers on exposed body parts e.g. face, arms, legs May be large number of lesions (can be up to 200 - can cause serious disability) Risk of superadded infections Causes scarring -> social prejudice (thus better to get bitten in less exposed areas)

Question 396

What does mucocutaneous Leishmaniasis cause

Answer 396

Partial/total destruction of mucous membranes of: - Nose - Mouth - Throat cavities - And tissues surrounding these sites Social stigma and rejection! Increased risk of recurrent bacterial pneumonia (people can subsequently die of sepsis) due to destruction of nose/palate

Question 397

What does Visceral Leishmaniasis cause

Answer 397

Affects lymph system so: - Irregular bouts of fever - Weight loss - Massive splenomegaly - Hepatomegally - Anaemia (secondary) - High fatality if untreated (100% within 2 years)

Question 398

Which organism causes trichomoniasis

Answer 398

Trichomonas vaginalis - protozoa STI ENDEMIC TO UK

Question 399

Trichomoniasis signs/symptoms

Answer 399

- Often asymptomatic - Dysuria - Yellow, frothy discharge

Question 400

How can Trichomoniasis be treated

Answer 400

With metronidazole - antibiotic

Question 401

What organism causes Giardiasis + type of spread

Answer 401

Giardia lamblia Faeco-oral spread esp linked to contaminated water

Question 402

Giardiasis signs/symps

Answer 402

DIarrhoea KEY FEATURES: Cramps, bloating, flatulence Can become lactose intolerant after infection

Question 403

Where is giardiasis more likely to occur

Answer 403

In a traveller In childcare settings e.g. nurseries These are KEY FEATURES

Question 404

How can giardiasis be diagnosed

Answer 404

Trophozoites (active - jellyfish with face)/cysts (inactive - round, thick wall) seen in stool Identifying clinical features

Question 405

How is giardiasis treated

Answer 405

Metronidazole - antibiotic

Question 406

What is the name of the main medically relevant amoeba? What disease does it cause? + spread

Answer 406

Entaemoeba histolytica (Amoeba that affects gut and destroys cells) Causes Amoebiasis (Amoebic dysentry! Bloody diarrhoea!) FAECO-ORAL SPREAD

Question 407

What does amoebiasis cause?

Answer 407

IMPORTANT: - Dysentry - Colitis - Liver and lung abscesses - Can live in gut asymptomatically

Question 408

How do amoeba move

Answer 408

They use pseudopoda - temporary projections of the cell - kinda just reach out with protrusions and squirm along like macrophages

Question 409

Why do entamoeba histolytica cause intestinal issues

Answer 409

The amoeba invades colon and consumes RBCs

Question 410

Risk factors for Amoebiasis

Answer 410

- Poor sanitary conditions/tropical countries - MSM (men who have sex with men)

Question 411

How can amoebiasis be diagnosed

Answer 411

Trophozoites/cysts seen in stool

Question 412

How is amoebiasis treated

Answer 412

METRONIDAZOLE

Question 413

Name the main sporozoa

Answer 413

- Cryptosporidium spp (Spore-like protozoa that affects crypts in intestine) - Toxoplasma gondii (remember as Toxic in plasma?) - Plasmodium spp (need to learn individual spp. - related to blood plasma)

Question 414

What disease does Cryptosporidium spp cause? Which species in particular are relevant in humans

Answer 414

Cryptosporidiosis (diarrhoeal) - C. Hominis and C. parvum (Homo species affecting and ‘small’ respectively)

Question 415

What are the symptoms of Cryptosporidiosis

Answer 415

- DIARRHOEA (watery but no blood) - Vomiting - Fever - Weight loss - Usually self-limiting but can be fatal in - immunocompromised

Question 416

How can cryptosporidiosis be diagnosed

Answer 416

Acid fast oocysts seen in stool

Question 417

How is Cryptosporidiosis spread

Answer 417

Waterborne (e.g. Fresh water swimming)

Question 418

How long does cryptosporidiosis last in healthy individuals

Answer 418

Usually 1-2 weeks

Question 419

What is cryptosporidiosis treated with in more severe cases

Answer 419

Nitazoxanide - antimicrobial

Question 420

What organism causes Toxoplasmosis?

Answer 420

Toxoplasma gondii (toxic plasma gon’ die?)

Question 421

How is Toxoplasmosis acquired?

Answer 421

- Ingestion of food contaminated with bradyzoits (tissue cysts) - e.g. rare beef/lamb, shellfish, unpasturised goats milk - Ingestion of oocysts via contact with FELINE faeces

Question 422

Toxoplasma gondii - what are their definitive hosts and intermediate hosts

Answer 422

- Only cats are definitive hosts (full cycle occurs, ingestion to excretion) - Other mammals including humans are intermediate hosts (parasite can be ingested but it becomes a tissue cyst so isn’t excreted)

Question 423

What occurs when toxoplasma gondii oocysts/bradyzoites are ingested

Answer 423

- Haematogenous spread - Invasion of tissues - Tissue cysts develop, primarily in muscles and neurons

Question 424

What can toxoplasmosis cause in immunocompromised

Answer 424

- Disseminated disease - Toxoplasma Encephalitis (inflammation of brain) - Chorioretinitis (inflammation of choroid lining of retina) - Can have devastating consequences in pregnancy: - Worst in first trimester - Causes congenital toxoplasmosis - Microcephaly - Hydrocephalus - Interuterine growth retardation - Miscarriage - Can be treated if picked up early enough - Counselling for termination may be offered

Question 425

Presentation of acute toxoplasmosis in healthy individual

Answer 425

- 90% often asymptomatic - 10% - glandular fever type illness

Question 426

Which organism causes Malaria?

Answer 426

Plasmodium spp - sporazoa protozoa - Plasmodium falciparum (most SEVERE, high mortality if untreated - through blood plasma - falciparum = small scythe) - Plasmodium ovale - Plasmodium vivax - Plasmodium malariae - Plasmodium knowlesi

Question 427

Incubation period for common malaria causing sporozoa

Answer 427

- Plasmodium falciparum - typically a month - Plasmodium ovale and vivax - up to a year

Question 428

Which organism transmits malaria

Answer 428

Female Anopheles mosquito

Question 429

How is malaria diagnosed?

Answer 429

- Light microscopy of blood film - will contain trophozoite - Thick and thin film done - Three blood films done on consecutive days (length of lifecycle) - First smear probs +ve in 95% of cases - Can also used rapid diagnostic tests that detect plasmodium antigens in blood

Question 430

Thick vs. thin blood films

Answer 430

- Thick film is sensitive but low res (e.g. for deciding if person has malaria or not) - Thin film higher res so can identify different species AND is used to work out parasitaemia percentage

Question 431

Symptoms of malaria

Answer 431

- FEVER!! - Chills - Headache - Myalgia - Fatigue - Diarrhoea - Vomiting - Abdo pain Can be variable in diff people but fever is most common

Question 432

Malaria signs

Answer 432

- Anaemia - Jaundice - Hepatosplenomegaly - ‘Black water fever’ (haemoglobinuria) - from haemolysis products in urine Some people may not LOOK ill

Question 433

Who are most at risk of getting the most unwell from malaria

Answer 433

Travellers and pregnant women

Question 434

Life cycle of malaria

Answer 434

- Mosquito ingests plasmodium gametocytes from biting infected human (is infected for rest of its 4 week lifespan) - Gametocytes develop in mosquito midgut and end as sporozoites in salivary glands - MOSQUITO BITES next human and injects sporozoites - Sporozoites now in human blood infect HEPATOCYTES - Infected hepatocytes develop into SCHIZONTS, which burst and infect RBCs causing ABDO PAIN - Plasmodium becomes trophozoite within RBC - Trophozoite develops into schizont which ruptures and re-infects more RBCs (causes CYCLICAL FEVER) - Causes HAEMOLYSIS so ANAEMIA and JAUNDICE (from BILIRUBINEMIA) and HAEMOGLOBINURIA - Blood stage usually lasts 48 hours - Some trophozoites develop into gametocytes which are taken up by another mosquito!

Question 435

What additional ability makes Plasmodium falciparum infection more severe + it's complications

Answer 435

- Causes OBSTRUCTED MICROCIRCULATION (typically in big organs) - Mostly due to PROINFLAMMATORY CYTOKINE CASCADE - stimulates endothelial activation which causes rolling of RBCs and endothelial cytoadherence - Also causes ROSETTING - clumping together of RBCs and platelets Results in “Complicated Malaria” - Cerebral malaria, - ARDS, - Renalfailure - Bleeding/Anaemia - Sepsis/Shock - Possibly other organ failure including heart - esp because of anaemia -> anaerobic -> LACTIC ACIDOSIS + HYPOGLYCAEMIA (reduced gluconeogenesis from liver damage + parasite uses up glucose)

Question 436

Causes and signs/symptoms of Cerebral malaria

Answer 436

VASCULAR OCCLUSION causes: - DROWSINESS - RAISED INTRACRANIAL PRESSURE - SEIZURES - COMA -> death Drowsiness can also be due to hypoglycaemia so check that too

Question 437

Causes and signs/symptoms of Acute Respiratory Distress Syndrome (ARDS!) due to complicated malaria

Answer 437

Direct effect of VASCULAR OCCLUSION: - Compensatory TACHYPNOEA due to ANAEMIA and LACTIC ACIDOSIS - INCREASED VASCULAR PERMEABILITY causing PULMONARY OEDEMA - All contribute to SOB and HYPOXIA

Question 438

Causes and signs/symptoms of Renal failure in complicated malaria

Answer 438

Directly due to VASCULAR OCCLUSION - Secondary HYPOPERFUSION due to DEHYDRATION from fever (which causes HYPOTENSION) - HAEMOLYSIS products can be NEPHROTOXIC Subsequently: - PROTEINURIA - FATIGUE - HAEMATURIA

Question 439

Causes of Bleeding in complicated malaria

Answer 439

- Platelet aggregation occurs which causes THROMBOCYTOPENIA - Generalised inflammation -> activation of coagulation cascade -> clotting factors used up -> DISSEMINATED INTRAVASCULAR COAGULATION (DIC) -> micro clots in blood and abnormal bleeding e.g. ABNORMAL EPISTAXIS (nose bleed) Worsening anaemia also contributes

Question 440

Causes of Shock in complicated Malaria

Answer 440

- PRO-INFLAMMATORY CASCADE occurs which causes VASODILATION - SEVERE ANAEMIA can cause CARDIOGENIC SHOCK - INCREASED VASC PERMEABILITY in the bowel can allow gram -ve bacteria from bowel into bloodstream -> causes GRAM -VE SEPSIS - Increased vascular permeability can also cause intravascular fluid leakage into “3rd space” - BLEEDING can cause HYPOVOLEMIA

Question 441

Signs and symptoms of shock

Answer 441

- HYPOTENSION - TACHYCARDIA - DROWSY - PALE

Question 442

Treatment for Complicated malaria?

Answer 442

IV ARTESUNATE (combination of quinine and doxycycline)

Question 443

Supportive measures for the extra complications of Complicated malaria

Answer 443

- Cerebral: antiepileptics - ARDS: oxygen, diuretics, ventilation - Renal failure: fluids, dialysis - Sepsis: broad spectrum antibiotics - Bleeding/Anaemia: blood products - Exchange transfusion if huge parasite burden

Question 444

How can relapses of malaria occur

Answer 444

P. ovale and vivex can form HYPNOZOITES in liver which can reactivate up to years later

Question 445

What additional treatment is given to eliminate hypnozoites after p. ovale/vivex infection

Answer 445

- PRIMAQUINE - CONTRAINDICTED in G6PD (glucose-6-phosphate dehydrogenase) DEFICIENCY - can cause HAEMOLYSIS

Question 446

Example of drug to treat acute malaria (uncomplicated)

Answer 446

Chloroquine

Question 447

When should you consider a possibility of malaria?

Answer 447

FEVER + RECENT TRAVEL

Question 448

What is the key principle of antibiotics

Answer 448

Only use antibiotics if they are actually needed

Question 449

What is an antibiotic

Answer 449

- Agents produced by micro-organisms that kill or inhibit the growth of other micro-organisms in high dilution - Work by binding to a target site on a microorganism - Most agents used now are semi-synthetic derivatives of antibiotics so the more correct term is antimicrobials

Question 450

Define target site (on a bacterium)

Answer 450

Points of biochemical reaction crucial to the survival of the bacterium

Question 451

Where can antibiotics bind to bacteria and what defines where they bind

Answer 451

- Crucial binding site varies with the ANTIBIOTIC CLASS - Some bind to ribosomes (affects protein synthesis) - Some bind to DNA or associated components (affects nucleic acid synthesis) - Some bind to cell wall (affect cell wall synthesis)

Question 452

Which classes of antibiotics affect cell wall synthesis

Answer 452

Beta lactams (contains beta lactam rings) - Penicillins - Cephalosporins - Carbapenems - Monobactams Glycopeptides

Question 453

Name the important penicillins

Answer 453

- Penicillin V - Penicillin G (Benzylpenicillin) - Flucloxacillin - Amoxicillin/Ampicillin - Piperacillin

Question 454

Name the important Cephalosporins

Answer 454

- Cefuroxime - Cefotaxime - Ceftriaxone - (Cefalexin) - (Ceftazidime

Question 455

Name the important carbapenams

Answer 455

- Meropenem - (Ertapenem) - (Imipenem)

Question 456

Name a relevant Monobactam

Answer 456

Aztreonam

Question 457

Name some important glycopeptides

Answer 457

Vancomycin Teicoplanin

Question 458

Which type of bacteria are more susceptible to beta lactams and glycopeptides

Answer 458

Beta lactams and glyopeptides work best on gram +ve as they have big cell wall

Question 459

Mechanism of action of beta lactams

Answer 459

- Bind covalently (and thus irreversibly) to PENICILIN BINDING PROTEINS - Cell wall synthesis (specifically peptidoglycan production) is disrupted - lysis occurs - Results in HYPO-OSMOTIC or ISO-OSMOTIC environment (fluid moves into cell and causes it to burst) - Only active against rapidly multiplying organisms

Question 460

Why are gram -ve bacteria less susceptible to beta-lactams

Answer 460

- Beta-lactams have to diffuse through the bacterial cell wall first to bind to the PBPs - Gram negative organism have additional LPS layer that decreases antibiotic penetration

Question 461

What causes the differences in the spectrum and activity of beta-lactam antibiotics

Answer 461

It is due to their relative affinity for different PBPs

Question 462

Which antibiotics affect nucleic acid synthesis/DNA functioning

Answer 462

- Rifampicin - METRONIDAZOLE - Fluoroquinolones (acts on DNA gyrase (and topoisomerase IV)) - CIRPROFLUXACIN - Levofluxacin - Moxifloxacin

Question 463

Which antibiotics affect protein synthesis (at ribosomes)

Answer 463

- Aminoglycosides (30s subunit) - Tetracyclines (works on 30s subunit) - Lincosamides (50s subunit) - Macrolides - Chloramphenicol

Question 464

What is the main aminoglycoside

Answer 464

GENTAMICIN - used for lots of different serious bacterial infections

Question 465

What is the main tetracycline

Answer 465

DOXYCLINE (also an antiprotozoal - used against malaria) - commonly used for chlamydia

Question 466

What is the main Lincosamides

Answer 466

CLINDAMYCIN - commonly used for patients allergic to penicillin

Question 467

What are the main Macrolides and what are they used for

Answer 467

Erythromycin CLARITHROMYCIN (also used for H. pylori infections) Azithromycin (also used for chlamydia) - commonly used for resp. And throat infections - also in uncomplicated skin infections and otitis media in paediatrics

Question 468

Which antibiotics affect Folate synthesis

Answer 468

- Sulphonamides (e.g. sulphamethoxazole) - TRIMETHOPRIM - Commonly used for UTIs - CO-TRIMOXAZOLE (combination of sulphamethoxazole and trimethoprim)

Question 469

What are bactericidal antibiotics

Answer 469

Agent that KILLS BACTERIA by INHIBITING CELL WALL SYNTHESIS Kill >99.9% in 18-24 hours

Question 470

What are bactericidal antibiotics useful for

Answer 470

- In infections where penetration to site of bacterial growth is poor (e.g. endocarditis) - In difficult to treat infections (e.g. in immunosuppressed patients) - Or infections that need to be eradicated quickly (e.g. meningitis and encephalitis, sepsis)

Question 471

Why does endocarditis require bactericidal antibiotics

Answer 471

- Infection is in a site where patient’s own immune system is unable to deal with bacteria - Bacteria are working alone - Bacteria within cardiac vegetations are at high concentrations, have lower rates of metabolism/cell division/are dormant - Surrounded by fibrin, platelets and possibly calcified material

Question 472

What is a negative side effect of bactericidal antibiotics

Answer 472

- Can lead to release of endotoxin from gram negative bacteria - Resulting increase in antigenic load causes an aggressive and dangerous inflammatory response - **gram negative bacterial sepsis** - Jarisch-Herxheimer reaction from spirochetes (e.g. in syphilis, leptospirosis etc.) - Also can cause toxin production -> **Toxic Shock Syndrome (s. aureus)** and **Pneumolysin release (s. pneumonia)**

Question 473

What do bacteriostatic antibiotics do

Answer 473

Inhibit bacterial growth Kill >90% in 18-24 hour

Question 474

How are bactericidal and bacteriostatic antibiotics defined (in terms of MBC and MIC)

Answer 474

- If the ratio of Minimum Bactericidal Concentration (MBC) to MINIMUM INHIBITORY CONCENTRATION (MIC) is >4 - the drug is defined as bacteriostatic - If the ratio of MBC to MIC is <4 the drug is defined as Bactericidal

Question 475

What types of antibiotics are bacteriostatic

Answer 475

Antibiotics that inhibit protein synthesis, DNA replication or metabolism

Question 476

How is MIC determined

Answer 476

- Test in tube dilution in lab - INCUBATE for 24 HOURS - Determine MIC based on TURBIDITY (how clear or cloudy the solution is)

Question 477

What does an antibiotic need to be able to do to work effectively

Answer 477

- It needs to attach to its binding target AND occupy an adequate number of binding sites (related to its conc within microbe) - CONCENTRATION present - It needs to remain at the binding site for a sufficient period of time for bacterial metabolic processes to be sufficiently inhibited - TIME it remains

Question 478

Two types of bacterial killing functioning by antibiotics

Answer 478

Time dependant killing Concentration dependent killing

Question 479

What is the key parameter for time dependent killing for antibiotics

Answer 479

- The TIME for which serum concs remain ABOVE the MIC during the dosing interval - t>MIC

Question 480

Which antibiotics use time dependant killing

Answer 480

Beta-lactams Clindamycin Macrolides Oxazolidinones (synthetic - used against resistant bacteria e.g. vancomycin resistant enterococcus, MRSA, M. tb)

Question 481

What is the key parameter in concentration dependent killing

Answer 481

How HIGH the conc is ABOVE the MIC Peak conc/MIC ratio

Question 482

Which antibiotics use conc-dependent killing

Answer 482

Aminoglycosides Quinolones

Question 483

Define pharmacokinetics

Answer 483

The activity of drugs in the body over a period of time. It is a function of: - Its RELEASE from dosage form, - ABSORPTION from site of administration into bloodstream, - DISTRIBUTION to various parts of the body, including site of action - its rate of ELIMINATION from body via metabolism (via liver) or excretion (via kidney) of unchanged drug

Question 484

Questions to ask when considering appropriateness of antibiotics for a certain site

Answer 484

- Which antibiotics will penetrate that site? - E.g. if pus has collected around the infected site there will be no direct blood supply and it will be difficult to get antibiotic to the site. Or in endocarditis as the bacteria is on the valves which depend on blood flowing past so hard to get antibiotic to stick - What is the pH of the site? - Is the antibiotic lipid soluble?

Question 485

What does dosage interval/duration of antibiotic depend on

Answer 485

Half life + elimination time

Question 486

How do bacteria resist antibiotics

Answer 486

- Change antibiotic target - Destroy antibiotic - Prevent antibiotic access - Remove antibiotic from bacteria

Question 487

Give examples of bacterial resistance due to changed antibiotic target

Answer 487

IMPORTANT - Flucloxacillin no longer able to bind to PBP of certain staph aureus (MRSA) - Wall component changes in enterococci reduce vancomycin binding (VRE) - Rifampin activity reduced by changes to RNA polymerase in M. TB (Multi drug resistant TB - MDR-TB)

Question 488

Examples of bacterial resistance via destroying/inactivated antibiotic

Answer 488

- Some bacteria have ‘BETA LACTAMASE’, an enzyme which HYDROLYSES the BETA LACTAM RING of penicillins and cephalosporins etc. - Staphylococci produce ‘penicillinase’ - inactivates penicillin (BUT NOT flucloxacillin) - Gram -VE bacteria PHOSPHORYLATE AND ACETYLATE Aminoglycosides (e.g. gentamicin)

Question 489

How do bacteria prevent antibiotic access

Answer 489

Modify the bacterial membrane porin channel size, numbers and selectivity

Question 490

Examples of bacterial resistance via preventing antibiotic access

Answer 490

- Pseudomonas aeruginosa against imipenem, - Gram negative bacteria against aminoglycosides

Question 491

Give examples of bacterial resistance via removal of antibiotic from bacteria

Answer 491

- S. aureus or S. pneumoniae resistance to fluoroquinolones - Enterobacteriacae resistance to tetracylines

Question 492

How do bacteria develop resistance

Answer 492

Intrinsic resistance Acquired resistance: - spontaneous gene mutation - horizontal/lateral gene transfer ** conjugation ** transduction ** transformation

Question 493

Characteristic of intrinsic resistance

Answer 493

All subpopulation of a species will be equally resistant

Question 494

Examples of intrinsic resistance

Answer 494

- Aerobic bacteria CANNOT reduce metronidazole to its active form (requires anaerobic pathway) - Vancomycin CANNOT penetrate outer membrane of GRAM NEGATIVE bacteria - Anaerobic bacteria lack oxidate metabolism which is required for aminoglycoside uptake - PBP in enterococci are not effectively bound by cephalisporins

Question 495

Example of resistnace via spontaneous gene mutation

Answer 495

M. TB - point mutation in the rifampin-binding region rpoB

Question 496

What occurs in conjugation (bacterial lateral gene transfer) + example

Answer 496

Sharing of extra-chromosomal DNA plasmids (via “bacteria sex”) New Delhi metallo-beta-lactamase, ESBLs (extended spectrum beta-lactamases)

Question 497

What occurs in transduction (bacterial lateral gene transfer) + example

Answer 497

Insertion of DNA via organisms like bacteriophages mecA genes for MRSA are acquired via a mobile genetic element called “staphylococcal cassette chromosome”

Question 498

What occurs in transformation (bacterial lateral gene transfer) + example

Answer 498

Picking up naked DNA from the environment Foreign DNA from S. mitis to S. pneumoniae conferring penicillin resistance

Question 499

Mode of resistance of MRSA

Answer 499

- Contains mecA gene - on Staphylococcal cassette chromosome mec (SSCmec) - acquired via transduction mediated by bacteriophage - Encodes PBP2a (penicillin binding protein 2a) - Confers resistance to all beta-lactams including flucloxillin

Question 500

Resistance acquisition of VRE

Answer 500

- Plasmid mediated - of gene encoding altered amino acid which prevents vancomycin binding - Promoted by cephalosporins

Question 501

Mode of aquisition + action of ESBL

Answer 501

Acquired via random mutation at active site Hydrolyse OXYIMINO side chains of CEPHALOSPORINS (cefotaxime, ceftriaxone, ceftazidime) and MONOBACTAMS (aztreonam)

Question 502

Specific ESBL strains

Answer 502

- TEM-1: E. coli, H. influenza, N. gonorrhoeae - SHV-1: K. pneumoniae - CTX-M: cephalosporinase in ENTEROBACTERIACEAE (even more extensive plasmid mediated ESBL) These strains still sensitive to BETA-LACTAMASE INHIBITORS

Question 503

AmpC beta-lactamase resistance functioning

Answer 503

- Broad spectrum penicillin, cephalosporin and monobactam resistance - RESISTANT to BETA-lactamase INHIBITOR - INDUCIBLE expression (gene turned on by antibiotic)

Question 504

Which bacteria have AmpC beta-lactamase resistance

Answer 504

encoded on the chromosome in bacteria such as Citrobacter spp., Serratia marcescens, Enterobacter spp.

Question 505

How can AmpC beta-lactamase resistant bacteria be treated

Answer 505

- With Quinolones or Trimethoprim - The previously last resort CARBAPENEMS - Agents like fosfomycin

Question 506

Examples of Carbapenem resistant enterobacteriaceae (CRE) + what do they produce

Answer 506

Metallo-β-lactamases - IMP or VIM – Pseudomonas aeruginosa, Acetinobacter spp. NDM-1 - E. Coli, Klebsiella pneumoniae OXA - (oxacillinases –Acetinobacter baumanii) KPC - (Klebsiella pneumoniae) Produce Carbapenemases

Question 507

Treatment options for CREs

Answer 507

- Very few and very toxic - Colistin, a polymyxin - Tigecycline (but not as monotherapy for bacteremia or respiratory infection as bacterostatic) - Fosfomycin or aminoglycosides in combo with other agents - **Meropenam 2g tid (high dose, prolonged 3h infusion if MIC 4-8mg/ml) with colistin/aminoglycoside** - Colistin and tigecycline - Combo therapy may be better

Question 508

Which antibiotics are given first for skin and soft tissue sepsis It is then discovered to be caused by Group A strep. What changes, if any, are made to the drug regimen?

Answer 508

First give broad spectrums: - Piperacillin/Tazobactam - Clindamycin Group A strep are treatable with penicillins: - de-escalate to BENZYLPENICILLIN + Clindamycin

Question 509

Factors to consider when deciding if an antibiotic is safe to use

Answer 509

- Intolerance (though this doesn’t necessarily contraindicate giving the antibiotic), allergy and anaphylaxis (this definitely would contraindicate) - Side effects - Age - Renal and Liver function - Pregnancy and breast feeding - Drug interactions - Risk of Clostridium difficile (greater risk for older patient)

Question 510

Which antibiotics would be the standard treatment for bacterial celullitis

Answer 510

Often caused by S. aureus or group A, C or G strep Use FLUCLOXACILLIN - covers beta haem strep AND s. Aureus - s. Aureus can be penicillin resistant

Question 511

When would it be more suitable to use cephalosporins than penicillins

Answer 511

- If they have a penicillin allergy - Against some resistant bacteria - Able to get into different parts of the body e.g. for meningitis

Question 512

Which antibiotics would you use for strep throat

Answer 512

- PO (per os i.e through the mouth) PENICILLIN - only works in mouth/throat area - IV BENZYLPENICILLIN (used for soft tissue infections - wounds, pharyngitis, resp tract, middle ear etc)

Question 513

Which antibiotics for S. pneumoniae caused pneumonia

Answer 513

PO AMOXICILLIN (Po penicillin can’t penetrate this far) IV BENZYLPENICILLIN

Question 514

How are glycopeptides administered

Answer 514

IV ONLY

Question 515

What are macrolides used for + how are they administered

Answer 515

- Macrolides are Clarithomycin and erythromycin - protein synthesis inhibitors - Active against GRAM +VE (s. Aureus, beta haem strep) and ATYPICAL PNEUMONIA pathogens (multiply intracelullarly e.g. legionella) - Use if penicillin allergy (for soft tissue/chest infections when can’t use fluclox/amox) - Use for SEVERE PNEUMONIA Adminestered orally or IV

Question 516

What are lincosamides used for + mode of adminsteration

Answer 516

- Clidamycin - affects protein synthesis - Works against pretty much all Gram +ve - DEACTIVATES EXOTOXINS - USE for CELLULITIS (if penicillin allergy) - USE for NECROTISING FASCIITIS Oral or IV

Question 517

What are Tetracyclines used for + mode of administration

Answer 517

- E.g. doxycycline - affects protein synthesis - BROAD SPECTRUM - but MAINLY GRAM +VE - USE for CELLULITIS (if penicillin allergy) - USE for PNEUMONIA Doxycyclin -> Orally

Question 518

What are Aminoglycosides used for + administration

Answer 518

E.g. Gentamicin - affects protein synthesis Active against GRAM -VE and STAPHS (used SYNERGISTICALLY to treat STREP) Use for UTIS Use SYNERGISTICALLY for INFECTIVE ENDOCARDITIS IV only

Question 519

What are Quinolones used for + adminestration

Answer 519

E.g. Ciprofluxacin - affects DNA synthesis Active against GRAM -VE more than gram +ve USE for UTIs and INTRA-ABDOMINAL INFECTIONS Use for Penicillin allergy Oral or IV

Question 520

What is Trimethoprim used for

Answer 520

Trimethoprim is an anti-metabolite (folate antagonist) It is a BROAD SPECTRUM antibiotic but is used MAINLY for GRAM -VE USE for UTIs

Question 521

What is Co-amoxiclav used for + administration

Answer 521

Active against S. AUREUS, STREPS, ENTEROCOCCI, GRAM -VE and ANAEROBES - Use for ASPIRATION PNEUMONIA, severe community acquired pneumonia (CAP), MORE RESISTANT URINARY organisms Oral or IV

Question 522

What is Piperacilliin/tazobactam used for + administratin

Answer 522

- VERY BROAD spectrum - NO COVER for ESBLs/AmpCs - USE for hospital acquired (HA)-pneumonia, SYSTEMIC PSEUDOMONAS, >65s abdominal infection, in IMMUNOCOMPROMISED IV only

Question 523

What is Cefuroxime used for + administration

Answer 523

- Active against GRAM +VEs and GRAM -VEs - **DOESN’T work against PSEUDOMONAS, ANAEROBES and ENTEROCOCCI** - USE for SOME SURGICAL PROPHYLAXIS, <65s intra abdominal infections, NON-SEVERE penicillin allergy IV only

Question 524

What is Meropenem used for

Answer 524

- BROAD ACTIVITY including ESBLs/AmpCs - USE for Hospital acquired infections (HAI) - the sickest/most at risk - RESISTANT GRAM -VE, immunocompromised - Used to be last resort antibiotic - still RESTRICTED access

Question 525

Define fungi

Answer 525

Eukaryotic, heterotrophic (eats other organisms) organisms with chitinous cell walls. They “move” via growth or through generation of spores (conidia) which are carried through air/water

Question 526

Yeast vs Mould

Answer 526

- Yeasts are small,single celled organisms - Divide by budding - Moulds form multicellular hyphae and spores - Some fungi can switch between both - dimorphic fungi

Question 527

Of the 5 million or so species of fungi that have been described. Why is it that only a few hundred are known to cause human infection

Answer 527

- Many fungi are unable to grow at 37 degrees celsius - Many are unable to evade innate and adaptive immune response Typically a disease of immunocompromised

Question 528

The vast majority of human mycoses are caused by very few genera of fungi. Which are these?

Answer 528

- Ascomycota (sac fungi phylum) - Aspergillus, Pneumocystis, Candida, Fusarium, Scedosporium - Basidiomycota (phylum of filamentous fungi) - Cryptococcus, Trichosporon - Mucormycota/zygomycetes (a subphylum or something)

Question 529

The overall burden of fungal disease is very high. Most people will have had a fungal infection. Give some examples of common fungal infections

Answer 529

Nappy rash and vuvlovaginal candidiasis Tinea pedis (athletes foot) Onychomycosis (fungal nail infections) Otitis externa Fungal asthma TInea capitis (ringworm of scalp) Fungal keratitis (corneal infection)

Question 530

What are the most common invasive fungal infections

Answer 530

- In immunocompromised people - Candida line infection - Invasive aspergillosis - Pneumocystis - Cryptococcosis - Mucormycosis - Post-surgical - Intra-abdominal infection - In healthy hosts - Fungal asthma - Travel associated infections e.g. Dimorphic fungi - Post-influenza aspergillosis (usually in ICU patients)

Question 531

Types of fungal diagnostic methods

Answer 531

Radiology for ASPERGILLUS + ZYGOMYCETES/MUCORMYCOTA - tho it is insensitive in early stages Microscopy - usually insensitive Culture (tho fungal cultures need to be kept longer and need special conditions to make sure they are not out competed by bacteria) - subsequent microscopy to ID (use tease mount technique/sellotape) - works ok for yeasts but usually poor for moulds Molecular - PCR - can get mixed results - Antigen tests

Question 532

Which antigen tests are used to diagnose fungal infections

Answer 532

- Cryptococcal Ag (EXCELLENT TEST) - Galactomannan (INSENSITIVE) - 1,3 Beta-D-glucan (POORLY SPECIFIC - present in candida, aspergillus and other common fungal infections) - assay very prone to contamination - Need at least **80pg/ml**

Question 533

What should an ideal diagnostic test be like?

Answer 533

- Non-invasive - Rapid and easy technically - Sensitive and reproducible - Specific - both in terms of pathogen and the significance of a positive result - Cheap VERY FEW TESTS FOR invasive fungal infections MEET THESE CRITERIA

Question 534

What ways can we ensure a drug will have selective toxicity for the pathogenic organism and not humans

Answer 534

- If drug target does not exist in humans - Target is significantly different to human analogue - Drug is concentrated in organism cell with respect to humans - Organism has increased permeability to compound - Modification of compound in organism or human cellular environment - Human cells are “rescued” from toxicity by alternative metabolic pathways MORE DIFFICULT TO DO THIS IN FUNGI AS THEY ARE EUKARYOTIC

Question 535

Key differences between fungal cell and human cell structure

Answer 535

Fungi have a cell wall which doesn’t exist in humans. It consists of: - mannoproteins - B 1,3 glucan - B 1,6 glucan - chitin Fungi have Ergosterol in their plasma membrane while humans have cholesterol

Question 536

Types + names of fungal treatments

Answer 536

- Drugs that affect DNA/RNA/protein synthesis - **Flucytosine** (don’t usually use as it is VERY TOXIC - fungal DNA etc. synthesis is similar to mammalian) - Drugs that affect the cell wall - **Echinocandins** - Drugs that affect the plasma membrane - **Amphotericin** - **Azoles = mainstay of fungal treatment (mainly safe)** - Terbinafine

Question 537

Which antifungal is most broad spectrum and has the highest barrier to resistance

Answer 537

Amphotericin B - typically only Pneumocystis jirovecii and potentially candida auris are resistant to it

Question 538

Pros and cons of Amphotericin B

Answer 538

- Pros: high barrier to resistance; broad spectrum - Cons: IV only, has many adverse effects (can be reduced BUT NOT ELIMINATED by EXPENSIVE liposomal formulations) - Renal, biochemical disturbance, infusion reactions, nephrotoxic Still commonly used

Question 539

Pros and cons of Echinocardins

Answer 539

- Pros: SAFE, effective against Candida (esp in ICU), some activity against Aspergillus - Cons: IV only, other types of fungi are resistant to it (and Candida parapsillosis could be resistant to it)

Question 540

Azole adverse events

Answer 540

All azoles are associated with transaminitis and GI toxicity - Long term FLUCONAZOLE -> ALOPECIA - ITRACONAZOLE - more PRONOUNCED GI symptoms - Nausea, abdominal pain, diarrhoea - 10% have to DISCONTINUE using itraconazole - Rare, life threatening liver failure - VORICONAZOLE: - associated with REVERSIBLE VISUAL DISTURBANCE in 30% - PHOTOSENSITIVITY in 1-2% - Recent reports of skin malignancy

Question 541

Fluconazole drug-drug interactions

Answer 541

FLUCONAZOLE - HYDROPHILIC and principally EXCRETED UNCHANGED - less significant interactions - Warfarin, phenytoin, calcineurin inhibitors, anxiolytics

Question 542

Itraconazole drug interactions

Answer 542

ITRACONAZOLE - potent CYP3A4 inhibitor - Warfarin, phenytoin, calcineurin inhibitors, anxiolytics AND steroids, statins, rifamycins,PIs

Question 543

Posaconazole drug interactions

Answer 543

POSACONAZOLE - mild CYP3A4 inhibitor - similar to Itraconazole

Question 544

Voriconazole drug interactions

Answer 544

VORICONAZOLE - inhibits a number of CYP enzymes - Affected drugs similar to itraconazole - E.g. Warfarin, phenytoin, calcineurin inhibitors, anxiolytics AND steroids, statins, rifamycins,PIs

Question 545

What is onychomycosis caused b

Answer 545

- Dermatophyte moulds (grow best at ~30 degrees and have evolved ability to hydrolyse keratinous debris in soil) - Most common type is TRICHOPHYTON RUBRUM

Question 546

Treatment for onychomycosis

Answer 546

- Usually Amorolfine - has ~20% complete cure rate (limited options) - Can use Systemic itraconazole or terbinafine - Presence of non-dermatophytes can lead to treatment failure - High failure rate with all therapies - around 40-60% cure rate - Takes a while to treat

Question 547

Diagnostic test used for onychomycosis

Answer 547

Microscopy is most specific BUT 30% of culture is negative

Question 548

DDx for onychomyosis (v broad)

Answer 548

Psoriasis Lichen planus Trauma Eczema Yellow nail syndrome Lamellar onychoschizia (lamellar splitting) Periungual squamous cell carcinoma/Bowens disease Malignant melanona Myxoid (mucous) cyst Alopecia areata

Question 549

How can samples be taken in onychomycosis

Answer 549

Proximal Clippings Material from underside of plate Skin scrapings from any Tinea (name of ringworm) Surface scrape of loose material Scrape away normal nail plate then curette proximal tissue or biopsy Results of sampling can be confusing

Question 550

How is pneumocystis detected

Answer 550

- Via PCR if able to get sample - Can’t grow it

Question 551

Pathogenesis of pneumocystis

Answer 551

- Infection/colonisation of healthy people is frequent and occurs early in life - Disease only develops if moderate-severely immunocompromised esp. HIV, transplants, steroids - Pneumocytis is a common clinical presentation of unknown HIV

Question 552

When should you suspect pneumocystis

Answer 552

- If they have hypoxia more severe than the chest x-ray would suggest - especially if the illness was gradual onset or they have the risk factors - Remember to consider it as a differential diagnosis in general

Question 553

What is the treatment for pneumocystis

Answer 553

Co-trimoxazole (plus steroid if hypoxic) - first line treatment