Phase 2 - Microbio

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 1μmBigger viruses ~0.3-0.8μmSmaller 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 rotavirusRickettsia 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 surfacesBacteria can also get into many organs and cause inflammation

Question 18

What do the colours of the gram stain signify

Answer 18

Purple - gram positivePink/red - gram negativepurPle - 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 rodsVibrio (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 membraneOuter membranePili/fimbriaeCell wallSome 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/lungsIt 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 membraneThick layer of peptidoglycan with lipoteichoic acid strands within itPotentially 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 outermembraneLipopolysaccerides (ENDOTOXIN) - composed of:- Lipid A- O antigen- Terminal sugarspotentially 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 layersGram 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 + 80CpH: <4 - 9Water/desiccation: 2 hours - 3 monthsLight: could be killed by UV

Question 31

What environment can spores survive in

Answer 31

Temperature: <-800C to 1200C pH: <4-9Water/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 minMycobacterium tuberculosis in broth or media:- 24 hoursMycobacterium 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

ENDOTOXINComponent of the outer membrane of GRAM NEGATIVE bacteria, eg lipopolysaccharidesEXOTOXINSecreted 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-specificexotoxins are labile in heat, endotoxins remain stableexotoxins have strong antigenicity, endotoxins have weak antigenicityexotoxins 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

1typically 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. pneumoniaeGenus 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. israeliiGenus NOCARDIA e.g. N. asteroidesGenus 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 VEILLONELLAAerobic: 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 twentiesN. 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. oralisetc.Beta-haemolytic:- S. pyogenes- S. agalactiaeetc.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 greenBeta-haemolytic fully lyses haem (via production of 2 pore-forming toxins) so turns blood agar clearNon-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 surgeryS. 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 throatS. pneumonia causes:- common pneumonia- meningitis in older peopleAlpha-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. botulinumetc.- PROPIONIBACTERIUM* P. acnesAerobic:- CORYNEBACTERIUM* C. diphtheriaeetc- LISTERIA * L. monocytogenesetc- BACILLUSB. 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. fragilisAerobic:- '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. choleraeCAMPYLOBACTER- e.g. C. jejuniHELICOBACTER

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 BRUCELLABORDETELLA- e.g. B. pertusissPASTEURELLA

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. recurrentisetc

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 +veCoagulase -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* EndocarditisToxin 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 intercourseVirulence 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 childrenSurface 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 mediaSkin and Soft tissue- Wound infections- Impetigo- cellulitis - puerperal feverScarlet fever- SPeA and M typeComplications- 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

PneumoniaOtitis medis (middle ear infection)SinusitisMeningitis

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)- peptidoglycanCytotoxin- 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/oThe 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. oralisVery 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 time3 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 acidsMycoplasmas don't have peptidoglycan- They are phylogenetically considered Gram positive

Question 113

The two types of virulence factors/pathogenicity determinants

Answer 113

Colonisation factorsToxins ('effectors')

Question 114

Name colonisation factors

Answer 114

Adhesins, invasins, nutrient acquisition, defence against the host

Question 115

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

Answer 115

- 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 116

Which bacteria are within the Phylum proteobacteria

Answer 116

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

Question 117

Characteristics of Enterobacteria

Answer 117

RodsMost 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 118

Name main members of enterobacteria?

Answer 118

ShigellaEscherichia (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 pestisEnterobacter spp.

Question 119

Which main enterobacteria are lactose use positive?

Answer 119

E. coliKlebsiella pneumoniae

Question 120

Which main enterobacteria are motile

Answer 120

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

Question 121

Which main enterobacteria are NOT motile?

Answer 121

Shigella flexneriKlebsiella pneumoniaeYersinia pestis at 37 degrees C

Question 122

How do you test Lactose phenotype?

Answer 122

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

Question 123

Which antigen is associated with flagella

Answer 123

H antigen

Question 124

How do you discriminate between similar bacteria like Salmonella and Shigella

Answer 124

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

Question 125

What is serotyping

Answer 125

Differentiating between specieses/strains by identifying cell surface antigens

Question 126

What is a serovar

Answer 126

Antigenically distinct varients of a single species

Question 127

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

Answer 127

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

Question 128

What is Escherichia coli normally

Answer 128

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

Question 129

Principal infections caused by pathogenic E. coli

Answer 129

(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 130

What are the species' of Shigella

Answer 130

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

Question 131

What does shigella cause

Answer 131

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

Question 132

Where is Shigella infection often found

Answer 132

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

Question 133

Symptoms of shigellosis

Answer 133

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

Question 134

Pathogenesis of Shigella infection

Answer 134

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 uptakeImportant virulaence factor: Shiga toxin

Question 135

Pathology of Shigella

Answer 135

- 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 136

What are the 2 specieces of Salmonella

Answer 136

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

Question 137

What does S. enterica cause

Answer 137

salmonellosis (usually from contaminated food/drink)3 forms:1. Gastroenteritis/enterocolitis2. Enteric fever3. Bacteraemia (bacteria in blood)

Question 138

Pathogenesis of salmonellosis

Answer 138

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/replicationIn Serovars Enteritidis and Typhimurium:- intestinal secretion and inflammatoryresponse are LOCALISED- DO NOT produce toxinsIn 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 139

Gastroenteritis/enterocolitis - causes and characteristics

Answer 139

Caused by serovars Enteritidis and TyphimuriumFrequent 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 140

Enteric fever - causes/characteristics

Answer 140

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

Question 141

What causes Bacteraemia

Answer 141

Serovars Cholerasuis and Dublin- it is uncommon

Question 142

Steps of gastroenteritis pathogenesis

Answer 142

1. Bacterial-mediated endocytosis 2. Induction of interleukin-8 release →3. Neutrophil recruitment and migration4. Neutrophil-induced tissue injury →5. Fluid and electrolyte loss → diarrhoeaInflammation/necrosis of gut mucosa

Question 143

Steps of enteric/typhoid fever pathogenesis

Answer 143

1. Bacterial-mediated endocytosis2. Transcytosis to basolateral membrane3. Survival in macrophage (MΦ) → systemic spread Initially, little damage to gut mucosa

Question 144

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

Answer 144

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

Question 145

Notable characteristic of Proteus mirabilis

Answer 145

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

Question 146

What does Proteus mirabilis cause

Answer 146

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 147

Characteristics of Klebsiella pneumoniae

Answer 147

- 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 benignMulti-drug resistant (resistant to carbapenems)

Question 148

What does Klebsiella pneumoniae cause

Answer 148

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

Question 149

Characteristics of Vibrio cholerae

Answer 149

- 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 150

What does vibrio cholerae cause

Answer 150

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

Question 151

History of Choleral pandemics

Answer 151

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 152

General pathology of Cholera (aquisition, incubation, consequence)

Answer 152

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 untreatedNo blood, pus or fever (i.e. not dysenteric)i.e. no invasion or damage to mucosa

Question 153

What can most cases of Cholera be treated by

Answer 153

Oral re-hydration therapy (ORT)

Question 154

What is the main virulence factor of V. cholerae

Answer 154

Cholera toxin

Question 155

Pathogenesis of Cholera (mechanism of cholera toxin)

Answer 155

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

Question 156

Characteristics of Pseudomonas aeruginosa

Answer 156

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 157

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

Answer 157

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 pneumoniaChronic infections:(i) In Cystic fibrosis (CF) patientsCommon denominator to all infections - compromised host defences

Question 158

What happens in cystic fibrosis (general overview)

Answer 158

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

Question 159

Most problematic source of infection for CF patients

Answer 159

P. aeruginosa

Question 160

Types of P. aeruginosa

Answer 160

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 161

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

Answer 161

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

Question 162

Characteristics of Haemophilius influenzae

Answer 162

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 163

Who are particularly susceptible to H. influenzae infection

Answer 163

Young children and adult smokers

Question 164

What infections can Haemofilius influenza cause

Answer 164

- 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 165

Diagnostic characteristics of H. influenxae

Answer 165

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

Question 166

Virulence determinants of H. influenzae

Answer 166

(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 167

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

Answer 167

Hib vaccine (HH. influenza type b)

Question 168

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

Answer 168

Legionnaires’ disease - severe inflammatory pneumonia (1-3% of all pneumonias) - 15-20% mortalityInfection 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 tooAffects immunocompromised (elderly, alcoholics, smokers etc.)

Question 169

What does Bordetella pertussis cause

Answer 169

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 170

Characteristics of B. pertussis

Answer 170

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 171

Diagnostic characteristics of B. pertussis

Answer 171

Short (sometimes oval) rods (coccobacilli)FastidiousGram negative

Question 172

Diagnostic characteristics of Neisseria

Answer 172

Non-flagellated diploccociFastidiousGram -ve

Question 173

Where can Nessieria be found in the environment

Answer 173

Humans are the only known reservoir

Question 174

Characteristics of N. meningitidis

Answer 174

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

Question 175

Pathogenesis of N. meningitidis

Answer 175

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 176

Virulence determinants of N. meningitidis

Answer 176

(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 177

What are non-blanching petechial pr purpuric rashes associated with

Answer 177

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

Question 178

What does N. gonorrhoeae cause

Answer 178

Gonorrhoea - second most common STD worldwide

Question 179

How is gonorrhoea transmitted

Answer 179

Person-to-person only

Question 180

How often can N. gonorrhoeae infection be asymptomatic

Answer 180

~10% men, ~50% women

Question 181

Characteristic infection presentation of gonorrhoea

Answer 181

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 preferenceCan transmit as conjunctivits to newborns

Question 182

Are gonococci capsulated or not

Answer 182

They are non-capsulated

Question 183

Helicobacter pylori appearance

Answer 183

spiral shape, tuft of polar flagella

Question 184

Where are H. pylori found in the body

Answer 184

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

Question 185

Incidence of H. pylori in global population

Answer 185

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

Question 186

Which diseases are H. pylori associated

Answer 186

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 187

Name of main bacteria in Phylum bacteroidetes

Answer 187

Bacteroides

Question 188

Characteristics of Bacteroides

Answer 188

Non-motile rodsObligate anaerobesCommensal flora of colon (most abundant organism in gut - 30-40% of total)Opportunistic

Question 189

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

Answer 189

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

Question 190

What infections can infections can Bacteroides cause

Answer 190

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

Question 191

Which Bacteroides species is most commonly responsible for infections

Answer 191

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

Question 192

Which genuses are in Phylum Chlamydiae

Answer 192

Chlamydia and Chlamydophila

Question 193

Characteristics of Chlamydia and Chlamydophila

Answer 193

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 194

Life cycle of Chlamydia and Chlamydophila

Answer 194

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 195

How many developmental stages in life cycle of Chlamydia/Chlamydophila

Answer 195

2- Elementary body stage- Reticulate body stage

Question 196

Form/characteristics of Chlamydia/Chlamydophila Elementary bodies

Answer 196

Rigid, dormant extracellular form~0.3 micrometers

Question 197

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

Answer 197

InfectiousEnter cell throughendocytosisprevent phagosome-lysosome fusion (so it can't be destroyed by host defence of cell)

Question 198

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

Answer 198

Non-infectiousReplicationAcquire nutrients from host cell

Question 199

Characteristic of Chlamydia/CHlamydophila reticulate body

Answer 199

fragile, metabolically active, intracellular formpleiomorphic~1.0 micrometers

Question 200

Medically important members of genus Chlamydia

Answer 200

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

Question 201

What disease does the Chlamydia trachomatis biovar trachoma cause

Answer 201

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

Question 202

What does C. trachomatis biovar genital tract cause

Answer 202

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 203

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

Answer 203

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

Question 204

Medically important members of Chlamydophila

Answer 204

C. pneumoniaeC. psittaci

Question 205

What does C. pneumoniae cause

Answer 205

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

Question 206

What does C. psittaci cause

Answer 206

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

Question 207

Spirochaete physical form

Answer 207

Long, slender, helical, highly flexible

Question 208

Characteristics of Spirochaetes

Answer 208

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

Question 209

Where is the spirochaete endoflagella located

Answer 209

Between peptidoglycan and outer membranePeriplasmic flagellaFixed at each end of bacterium and confers shapeOverlap in centre of bacterium

Question 210

Characteristics of spirochaete endoflagella function

Answer 210

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

Question 211

What are the 3 medically important members of Spirochaetes

Answer 211

Borrelia burgdorferiLeptospira interrogansTreponema pallidum

Question 212

What does Borrelia burgdorferi cause

Answer 212

Lyme disease

Question 213

How is Lyme disease transmitted

Answer 213

Via ticksB.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 214

Symptoms of Lyme disease

Answer 214

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

Question 215

How can lyme disease spread within the human body

Answer 215

dissemination via lymphatics/blood to other organs

Question 216

What does leptospira interrogans cause

Answer 216

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

Question 217

How is leptospirosis acquired?

Answer 217

Contact of infected animal urine with mucous membrane or abraded skin

Question 218

What does treponema pallidum cause

Answer 218

Syphilis

Question 219

How many stages of syphilis (treponema pallidum infection)

Answer 219

3Primary stageSecondary stageTertiary stage

Question 220

What occurs in primary stage syphilis (treponema pallidum infection)

Answer 220

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 221

What occurs in secondary stage syphilis (treponema pallidum infection)

Answer 221

Systemicskin (rash), swollen lymph nodes, joint pains, muscle aches, headache, feverOccurs at 1-3 months post-infectionHighly transmissible~50% of cases are at secondary stage

Question 222

What occurs in tertiary stage syphilis (treponema pallidum infection)

Answer 222

‘Gummas’ (granulomas) in bone and soft tissueCardiovascular syphilis (affects aorta)Neurosyphilis (affects brain and spinal cord)Occurs several years post-infectionNon-infectious

Question 223

How can syphilis be treated

Answer 223

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

Question 224

Name mycobacteria of medical importance and their relevant medical condition

Answer 224

M. tuberculosis - tuberculosisM. leprae - LeprosyM. 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 infectionsM. marinum - fish tank granuloma (asymptomatic in tropical fish - skin conditions in humans)

Question 225

Are most mycobacteria environmental or human organisms

Answer 225

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

Question 226

How is leprosy (m. leprae) communicated

Answer 226

Through respiratory mediums Only infectious in early respiratory period

Question 227

What effect does leprosy have on humans

Answer 227

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

Question 228

What socioeconomic factor is leprosy associated with

Answer 228

poverty

Question 229

Stages of Buruli ulcer (m. ulcerans infection)

Answer 229

NoduleSmall ulcerLarge ulcerBone destruction (causes deformation)

Question 230

What is severe Buruli ulcer associated with

Answer 230

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

Question 231

Characteristics of TB

Answer 231

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

Question 232

Mycobacteria physical appearance

Answer 232

Slightly curved, beaded bacilli

Question 233

What makes mycobacteria resistant to gram stain?

Answer 233

High lipid content with mycolic acid in cell walls

Question 234

Ziehl-Neelsen stain process

Answer 234

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

Question 235

How many bacilli are needed for a diagnosis

Answer 235

10 000 bacilli per ml of sputum

Question 236

Characteristics of mycobacteria

Answer 236

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

Question 237

Key components of mycobacteria cell wall

Answer 237

Mycolic acidsLipoarabinomannan

Question 238

How fast do mycobacteria grow

Answer 238

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 239

What is generation time?

Answer 239

Time taken for bacterial population to double in number

Question 240

How is TB transmitted

Answer 240

aerosol transmission

Question 241

What occurs in primary TB?

Answer 241

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

Question 242

What is latant TB

Answer 242

Where Primary infection is controlled but cell mediated immune response from T cells persitsNo 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 testCan remain in the body in this form for decades

Question 243

What occurs in Pulmonary TB

Answer 243

Can be post-primary (immediately after primary infection) or after reactivationGranulomas 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 upMay spread in lungs causing other lesions

Question 244

What are granulomas dependant on

Answer 244

A sufficient number of CD4 cells and TNF alpha being present

Question 245

What increases risk of TB becoming active

Answer 245

ImmunosuppressionAnti-TNF therapies (given for chronic inflammation)

Question 246

What is a primary complex in TB

Answer 246

Consists of granuloma, lymphatics and lymph nodes

Question 247

What issues can TB cause when it spreads beyond lungs

Answer 247

TB meningitisMiliary TBPleural TBBone and joint TBGenito-urinary TB

Question 248

How can TB be spread beyond lungs

Answer 248

Carried by macrophages which then move around body

Question 249

What does TB of spine cause?

Answer 249

Bent gibbus formation

Question 250

Immunological response to mycobacteria

Answer 250

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

Question 251

What does effective immunity to M. TB require

Answer 251

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 252

What does the granuloma consist of

Answer 252

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

Question 253

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

Answer 253

Mycobacteria shut down metabolically in order to survive - dormancyBut 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 254

What needs to be done first when trying to culture mycobacteria

Answer 254

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

Question 255

What methods can be used to culture mycobacteria

Answer 255

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

Question 256

What allows more rapid diagnosis of mycobacteria

Answer 256

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

Question 257

Name of Nucleic acid detection test used for mycobacteria

Answer 257

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

Question 258

What does the GeneXpert MTB/RIF cartridge based test do

Answer 258

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

Question 259

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

Answer 259

131 bacilli/ml

Question 260

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

Answer 260

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

Question 261

Is M. TB fastidious?

Answer 261

yes

Question 262

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

Answer 262

if TB is latent

Question 263

How can latent TB be recognised

Answer 263

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

Question 264

What is the downside of tuberculin/Mantoux test

Answer 264

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

Question 265

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

Answer 265

3-9 weeks

Question 266

Positive and negative effects of T cell response stimulation in TB

Answer 266

+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 267

Standard drug therapy for TB

Answer 267

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

Question 268

Second line treatment for TB

Answer 268

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

Question 269

How long does TB treatment take

Answer 269

4-9 months of combination therapy

Question 270

What are the resistance mechanisms of M. TB to drugs

Answer 270

Drug inactivation:- Mtb produces beta- lactamaseDrug titration:- Target overproductionAlteration of drug target:- Missense mutationsAltered cell envelope:- Increased permeability and drug efflux

Question 271

Multi-drug resistant TB: cause and characteristic

Answer 271

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

Question 272

Treating XDR-TB

Answer 272

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

Question 273

How do viruses cause disease

Answer 273

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

Question 274

What is the leading cause of death world wide

Answer 274

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

Question 275

Importance of viral infections in the UK

Answer 275

- 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 276

Which viruses can lie latent and reactivate upon immunosuppression

Answer 276

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 277

Which viruses are herpes class

Answer 277

- 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 278

What is a virus?

Answer 278

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

Question 279

Range of sizes of human viruses

Answer 279

20 to 260nm in diameterPoxviruses are some of the biggestParvovirus is the smallest

Question 280

Viruses vs Bacteria

Answer 280

- 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 281

Are DNA or RNA viruses typically hardier

Answer 281

DNA viruses

Question 282

What are virions

Answer 282

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

Question 283

Different shapes of viruses

Answer 283

- 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 284

Different types of viral external structure

Answer 284

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

Question 285

What would you examine when detecting a new virus

Answer 285

Genetic sequence

Question 286

Stages of viral replication

Answer 286

1. ATTACHMENT to specific receptor2. CELL ENTRY3. HOST CELL INTERACTION and REPLICATION4. ASSEMBLY OF VIRION5. RELEASE OF NEW VIRUS PARTICLES

Question 287

What does the attachment receptor of a virus dictate

Answer 287

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 288

What happens during cell entry by a virus

Answer 288

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

Question 289

What happens during host cell interaction and replication of a virus

Answer 289

- 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 290

What does translation of viral mRNA produce

Answer 290

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

Question 291

Where can assembly of virion occur within host cell

Answer 291

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

Question 292

How can new virus particles be released from host cell?

Answer 292

- 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 293

Example of direct destruction of host cells by a virus

Answer 293

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

Question 294

Example of virus causing disease by modification of host cell

Answer 294

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

Question 295

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

Answer 295

Hep B- Causes hepatocytes to be attacked by cytotoxic T lymphocytesResults 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 296

Example of virus causing damage through cell proliferation

Answer 296

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 297

Example of virus causing damage through evasion of host defences

Answer 297

At a cellular level:- Latency e.g. herpesviridae- Cell-cell spread e.g. measles, HIVAt 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 298

Where does each of the main herpes viruses lie dormant

Answer 298

- 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 299

What are the advantages of direct cell-cell spread

Answer 299

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

Question 300

What is antigenic variability

Answer 300

Ability to change surface antigens to evade host immune systemThrough mutations during replication

Question 301

How does prevention of host cell apoptosis by virus cause damage

Answer 301

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 302

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

Answer 302

- 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 303

How can viruses interfere with host cell antigen processing pathways

Answer 303

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

Question 304

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

Answer 304

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

Question 305

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

Answer 305

HSVSkin: - Orofacial herpes- Genital herpes- Herpetic whitlow- Erythema multiforme- Herpes gladiatorumVisceral:- Oesophagitis- Pneumonitis- HepatitisCNS: - Meningitis- Encephalitis- Transverse myelitisEye: - Conjunctivitis- KeratitisJC virus:CNS - Progressive multifocal leukoencephalopathy

Question 306

Which viruses can cause common cold

Answer 306

- Rhinovirus- Parainfluenza virus- Respiratory syncytial virus

Question 307

Which viruses can cause eye infections

Answer 307

- Herpes Simplex- Adenovirus- CMV

Question 308

Which viruses can cause Encephalitis/meningitis

Answer 308

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

Question 309

Which viruses can cause pharyngitis

Answer 309

- Adenovirus- EBV- CMV

Question 310

Which viruses can cause gastroenteritis

Answer 310

- Adenovirus- Rotavirus- Norovirus- Astrovirus- Coronavirus

Question 311

Which viruses can cause skin infections

Answer 311

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

Question 312

Which viruses cause sexually transmitted diseases

Answer 312

Herpes simplex type 2HPVHIV

Question 313

Which viruses can cause gingivostomatitis

Answer 313

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

Question 314

Which viruses can cause pneumonia

Answer 314

Influenza virus type A and BParainfluenza virusResp syncytial virusAdenovirusSARS coronavirus

Question 315

Which viruses can cause Myelitis

Answer 315

Poliovirus(HTLV-I)

Question 316

Which viruses cause pancreatitis

Answer 316

Coxsackie B virus

Question 317

Which virus can cause cardiovascular infection

Answer 317

Coxsackie B virus

Question 318

What are the diagnostic tests for detecting viruses

Answer 318

- 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 319

Key points about viruses

Answer 319

- 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 320

What does the Varicella Zoster Virus cause

Answer 320

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

Question 321

What does a VZV particle consist of

Answer 321

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

Question 322

Infection timeline of VZV

Answer 322

- 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 323

When is chickenpox most infectious

Answer 323

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

Question 324

Where does VZV replicate in body

Answer 324

Nasopharynx - present in nasal secretions

Question 325

How can VZV be transmitted

Answer 325

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

Question 326

Epidemiology of chickenpox

Answer 326

- 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 327

Risk groups for chickenpox

Answer 327

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

Question 328

Socioeconomic issue of endemic/chronic illnesses

Answer 328

Lots of lost school days and sick days from workDecrease productivity

Question 329

Progressive stages of chickenpox blister

Answer 329

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

Question 330

Distribution of chickenpox rash

Answer 330

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

Question 331

Characteristics of smallpox rash

Answer 331

- 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 332

What is something that is pathognomonic to chickenpox

Answer 332

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

Question 333

Diagnosis of chickenpox

Answer 333

- 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 334

Complications of chickenpox

Answer 334

- 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 syndromeRARE in children - MORE COMMON in adults

Question 335

What is the most common complication of chickenpox in adults

Answer 335

Chickenpox pneumonitisAffects 15% of healthy adults30% risk in lung disease/smoker30% mortality untreated6% mortality even with treatment

Question 336

Treatment for Varicella pneumonitis

Answer 336

- 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 337

How common is foetal infection of VZV in pregnancy

Answer 337

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

Question 338

Characteristics of foetal infection of chickenpox

Answer 338

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

Question 339

Potentially severe defects that can occur as complications of FVS

Answer 339

- 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 340

How are serum samples collected

Answer 340

- 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 341

When are initial serum samples taken in pregancy

Answer 341

~10-12 weeks pregnant

Question 342

Why are archived serum samples useful

Answer 342

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

Question 343

How does shingles reactivate as a unilateral rash

Answer 343

- 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 344

What type of viruses is dormancy and reactivation more common in

Answer 344

DNA viruses

Question 345

Characteristic onset of shingles

Answer 345

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

Question 346

Pain relief for shingles rash

Answer 346

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

Question 347

Sites of shingles reactivation

Answer 347

- 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 348

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

Answer 348

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

Question 349

What is the Hutchinson sign and what does it indicate

Answer 349

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

Question 350

Complications/signs of shingles becoming complicated

Answer 350

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

Question 351

Complications of herpes virus in people with atopic dermatitis/eczema

Answer 351

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

Question 352

What do enteroviruses cause

Answer 352

Hand foot and mouth disease- Shed enteroviruses in stool

Question 353

What pathologies cause rash on palms and soles of feet

Answer 353

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

Question 354

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

Answer 354

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

Question 355

Complications of parvovirus B19

Answer 355

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

Question 356

Treatment for hydrops fetalis

Answer 356

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 357

How do you test for hydrops fetalis

Answer 357

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

Question 358

Characteristics of parvovirus B19 rash

Answer 358

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

Question 359

What rash does HHV-6 cause

Answer 359

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

Question 360

Characteristics of HSV rashes

Answer 360

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

Question 361

Typical locations of HSV1 and HSV2 rashes

Answer 361

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

Question 362

Complications of HSV in immunosuppressed patients

Answer 362

Mucositis- Sore areas in mouth - mucosal epithelium is shedBugs can target these shed areas - secondary infectionsE.g. candida plaques

Question 363

Name a common pox virus, especially in children

Answer 363

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

Question 364

How can moluscum contagiosum be treated

Answer 364

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

Question 365

Which part of moluscum contagiosum often reactivates in immunosuppressed people

Answer 365

Lesions around eyes

Question 366

Which age group is primary cytomegalovirus infection most common in

Answer 366

Teens and 20s

Question 367

Diagnostic appearance of Primary CMV

Answer 367

Macular rashLymphadenopathy- Atypical lymphocytes (sticky, destructive, spread out)

Question 368

Complications of CMV reactivation

Answer 368

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

Question 369

Histological hallmark of CMV

Answer 369

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

Question 370

How is CMV treated

Answer 370

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

Question 371

What does measles cause

Answer 371

- 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 372

What do the local health protection unit control

Answer 372

Cough, coriza, conjunctivitis, diarreah, immune control

Question 373

How transmissible is measles

Answer 373

R0 = 16 (very high)100 in unvaccinated population

Question 374

Characteristic skin presentation of Dengue shock syndrome

Answer 374

Significant bruises/swelling from internal bleeding

Question 375

Which gram +ve bacteria can cause cellulitis

Answer 375

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

Question 376

Which gram +ve bacteria can cause pharyngitis/strep throat

Answer 376

Group A, C, G strep

Question 377

Define protozoa

Answer 377

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

Question 378

What are the 5 major groups of protozoa

Answer 378

FlagellateAmoebaSporozoaMicrosporidiaCiliate

Question 379

List main flagellate protozoa

Answer 379

- 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 380

Which protozoa cause African trypanosomiasis?

Answer 380

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

Question 381

Which organism transmits African trypanosomiasis

Answer 381

Tsetse fly (via bite)

Question 382

What does African trypanosomiasis cause

Answer 382

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

Question 383

How is African Trypanosomiasis diagnosed

Answer 383

Via blood film or CSF

Question 384

Which protazoa causes American trypanosomiasis (Chagas disease)

Answer 384

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

Question 385

How is american trypanosomiasis spread

Answer 385

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

Question 386

Symptoms of American Trypanosomiasis (Chagas disease)

Answer 386

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 387

How is Chagas disease diagnosed

Answer 387

- 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 388

Important types of trypanosomatida

Answer 388

- 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 389

Can Chagas disease be treated

Answer 389

Can be treated effectively if acuteCANNOT effectively treat once chronic - can only provide supportive treatments e.g. pacemaker, antiarrhythmias etc.

Question 390

Which organisms cause Leishmaniasis

Answer 390

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

Question 391

How is leishmaniasis spread?

Answer 391

Via bite of sand fly

Question 392

How is Leishmaniasis diagnosed

Answer 392

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

Question 393

What are the 3 clinical pictures of Leishman

Answer 393

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

Question 394

What does cutaneous Leishmaniasis cause

Answer 394

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

Question 395

What does mucocutaneous Leishmaniasis cause

Answer 395

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

Question 396

What does Visceral Leishmaniasis cause

Answer 396

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

Question 397

Which organism causes trichomoniasis

Answer 397

Trichomonas vaginalis - protozoaSTI ENDEMIC TO UK

Question 398

Trichomoniasis signs/symptoms

Answer 398

- Often asymptomatic- Dysuria- Yellow, frothy discharge

Question 399

How can Trichomoniasis be treated

Answer 399

With metronidazole - antibiotic

Question 400

What organism causes Giardiasis + type of spread

Answer 400

Giardia lambliaFaeco-oral spread esp linked to contaminated water

Question 401

Giardiasis signs/symps

Answer 401

DIarrhoeaKEY FEATURES: Cramps, bloating, flatulenceCan become lactose intolerant after infection

Question 402

Where is giardiasis more likely to occur

Answer 402

In a traveller In childcare settings e.g. nurseriesThese are KEY FEATURES

Question 403

How can giardiasis be diagnosed

Answer 403

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

Question 404

How is giardiasis treated

Answer 404

Metronidazole - antibiotic

Question 405

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

Answer 405

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

Question 406

What does amoebiasis cause?

Answer 406

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

Question 407

How do amoeba move

Answer 407

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

Question 408

Why do entamoeba histolytica cause intestinal issues

Answer 408

The amoeba invades colon and consumes RBCs

Question 409

Risk factors for Amoebiasis

Answer 409

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

Question 410

How can amoebiasis be diagnosed

Answer 410

Trophozoites/cysts seen in stool

Question 411

How is amoebiasis treated

Answer 411

METRONIDAZOLE

Question 412

Name the main sporozoa

Answer 412

- 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 413

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

Answer 413

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

Question 414

What are the symptoms of Cryptosporidiosis

Answer 414

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

Question 415

How can cryptosporidiosis be diagnosed

Answer 415

Acid fast oocysts seen in stool

Question 416

How is Cryptosporidiosis spread

Answer 416

Waterborne (e.g. Fresh water swimming)

Question 417

How long does cryptosporidiosis last in healthy individuals

Answer 417

Usually 1-2 weeks

Question 418

What is cryptosporidiosis treated with in more severe cases

Answer 418

Nitazoxanide - antimicrobial

Question 419

What organism causes Toxoplasmosis?

Answer 419

Toxoplasma gondii (toxic plasma gon’ die?)

Question 420

How is Toxoplasmosis acquired?

Answer 420

- 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 421

Toxoplasma gondii - what are their definitive hosts and intermediate hosts

Answer 421

- 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 422

What occurs when toxoplasma gondii oocysts/bradyzoites are ingested

Answer 422

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

Question 423

What can toxoplasmosis cause in immunocompromised

Answer 423

- 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 424

Presentation of acute toxoplasmosis in healthy individual

Answer 424

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

Question 425

Which organism causes Malaria?

Answer 425

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 426

Incubation period for common malaria causing sporozoa

Answer 426

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

Question 427

Which organism transmits malaria

Answer 427

Female Anopheles mosquito

Question 428

How is malaria diagnosed?

Answer 428

- 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 429

Thick vs. thin blood films

Answer 429

- 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 430

Symptoms of malaria

Answer 430

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

Question 431

Malaria signs

Answer 431

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

Question 432

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

Answer 432

Travellers and pregnant women

Question 433

Life cycle of malaria

Answer 433

- 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 434

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

Answer 434

- 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 plateletsResults 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 435

Causes and signs/symptoms of Cerebral malaria

Answer 435

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

Question 436

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

Answer 436

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 437

Causes and signs/symptoms of Renal failure in complicated malaria

Answer 437

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

Question 438

Causes of Bleeding in complicated malaria

Answer 438

- 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 439

Causes of Shock in complicated Malaria

Answer 439

- 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 440

Signs and symptoms of shock

Answer 440

- HYPOTENSION- TACHYCARDIA- DROWSY- PALE

Question 441

Treatment for Complicated malaria?

Answer 441

IV ARTESUNATE (combination of quinine and doxycycline)

Question 442

Supportive measures for the extra complications of Complicated malaria

Answer 442

- 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 443

How can relapses of malaria occur

Answer 443

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

Question 444

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

Answer 444

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

Question 445

Example of drug to treat acute malaria (uncomplicated)

Answer 445

Chloroquine

Question 446

When should you consider a possibility of malaria?

Answer 446

FEVER + RECENT TRAVEL

Question 447

What is the key principle of antibiotics

Answer 447

Only use antibiotics if they are actually needed

Question 448

What is an antibiotic

Answer 448

- 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 449

Define target site (on a bacterium)

Answer 449

Points of biochemical reaction crucial to the survival of the bacterium

Question 450

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

Answer 450

- 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 451

Which classes of antibiotics affect cell wall synthesis

Answer 451

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

Question 452

Name the important penicillins

Answer 452

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

Question 453

Name the important Cephalosporins

Answer 453

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

Question 454

Name the important carbapenams

Answer 454

- Meropenem- (Ertapenem)- (Imipenem)

Question 455

Name a relevant Monobactam

Answer 455

Aztreonam

Question 456

Name some important glycopeptides

Answer 456

VancomycinTeicoplanin

Question 457

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

Answer 457

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

Question 458

Mechanism of action of beta lactams

Answer 458

- 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 459

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

Answer 459

- 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 460

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

Answer 460

It is due to their relative affinity for different PBPs

Question 461

Which antibiotics affect nucleic acid synthesis/DNA functioning

Answer 461

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

Question 462

Which antibiotics affect protein synthesis (at ribosomes)

Answer 462

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

Question 463

What is the main aminoglycoside

Answer 463

GENTAMICIN- used for lots of different serious bacterial infections

Question 464

What is the main tetracycline

Answer 464

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

Question 465

What is the main Lincosamides

Answer 465

CLINDAMYCIN - commonly used for patients allergic to penicillin

Question 466

What are the main Macrolides and what are they used for

Answer 466

ErythromycinCLARITHROMYCIN (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 467

Which antibiotics affect Folate synthesis

Answer 467

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

Question 468

What are bactericidal antibiotics

Answer 468

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

Question 469

What are bactericidal antibiotics useful for

Answer 469

- 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 470

Why does endocarditis require bactericidal antibiotics

Answer 470

- 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 471

What is a negative side effect of bactericidal antibiotics

Answer 471

- 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 472

What do bacteriostatic antibiotics do

Answer 472

Inhibit bacterial growthKill >90% in 18-24 hour

Question 473

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

Answer 473

- 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 474

What types of antibiotics are bacteriostatic

Answer 474

Antibiotics that inhibit protein synthesis, DNA replication or metabolism

Question 475

How is MIC determined

Answer 475

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

Question 476

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

Answer 476

- 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 477

Two types of bacterial killing functioning by antibiotics

Answer 477

Time dependant killingConcentration dependent killing

Question 478

What is the key parameter for time dependent killing for antibiotics

Answer 478

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

Question 479

Which antibiotics use time dependant killing

Answer 479

Beta-lactamsClindamycinMacrolidesOxazolidinones (synthetic - used against resistant bacteria e.g. vancomycin resistant enterococcus, MRSA, M. tb)

Question 480

What is the key parameter in concentration dependent killing

Answer 480

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

Question 481

Which antibiotics use conc-dependent killing

Answer 481

AminoglycosidesQuinolones

Question 482

Define pharmacokinetics

Answer 482

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 483

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

Answer 483

- 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 484

What does dosage interval/duration of antibiotic depend on

Answer 484

Half life + elimination time

Question 485

How do bacteria resist antibiotics

Answer 485

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

Question 486

Give examples of bacterial resistance due to changed antibiotic target

Answer 486

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 487

Examples of bacterial resistance via destroying/inactivated antibiotic

Answer 487

- 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 488

How do bacteria prevent antibiotic access

Answer 488

Modify the bacterial membrane porin channel size, numbers and selectivity

Question 489

Examples of bacterial resistance via preventing antibiotic access

Answer 489

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

Question 490

Give examples of bacterial resistance via removal of antibiotic from bacteria

Answer 490

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

Question 491

How do bacteria develop resistance

Answer 491

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

Question 492

Characteristic of intrinsic resistance

Answer 492

All subpopulation of a species will be equally resistant

Question 493

Examples of intrinsic resistance

Answer 493

- 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 494

Example of resistnace via spontaneous gene mutation

Answer 494

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

Question 495

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

Answer 495

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

Question 496

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

Answer 496

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

Question 497

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

Answer 497

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

Question 498

Mode of resistance of MRSA

Answer 498

- 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 499

Resistance acquisition of VRE

Answer 499

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

Question 500

Mode of aquisition + action of ESBL

Answer 500

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