Microbiology KP notes Flashcards

(725 cards)

1
Q

what is the procedure for the Gram stain?

A
  • apply a primary stain such as crystal violet (purple) to heat fixed bacteria
  • add iodine which binds to crystal violet and helps fix it to the cell wall
  • decolorise with ethanol or acetone
  • counterstain with safranin (pink)
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2
Q

what are the results of the Gram stain?

A
  • in gram-negative bacteria, the decoloriser interacts with the lipids and cells lose their outer lipopolysaccharide membrane
    and the crystal violet-iodide (CV-I) complexes, thus they appear pink with counterstain
  • in gram-positive bacteria, the decoloriser dehydrates the cell
    wall and the CV-I gets trapped in the multi-layered peptidoglycan resulting in a purple appearance with counterstain

Gram positive = purple
Gram negative = pink

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3
Q

what is the Ziehl-Neelsen stain? what are the results?

A
  • Gram stain can differentiate most bacteria
  • but mycobacteria e.g. TB are acid-fast bacilli that do not take up the gram stain
  • instead they take up a stain called Ziehl-Neelsen

acid-fast bacilli = red e.g. Mycobacterium
non acid-fast bacilli = blue e.g. E.coli

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4
Q

what is the catalase test? what are the results?

A

• essentially add H2O2 to bacteria and see for bubbling reaction (positive reaction)
• used to differentiate between staphylococci
and streptococci
• Staphylococci are catalase positive
• Streptococci are catalase negative
• many Gram negative bacteria e.g. E.coli and fungi (aspergillus spp.) are catalase positive

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5
Q

what is the coagulase test? what are the results?

A
  • coagulase is an enzyme produced by Staphylococcus. aureus that converts (soluble) fibrinogen in plasma to (insoluble) fibrin
  • other staphylococci do not produce coagulase, e.g. S. epidermis
  • thus this test distinguishes S. aureus (coagulase positive) from other staphylococci (coagulase negative)
  • S. aureus is coagulase positive = clumping
  • other staphylococci are coagulase negative = no clumping
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6
Q

what is the haemolysis test?

A
  • haemolysis is the ability of bacteria to break down red blood cells in blood agar
  • it requires the expression of haemolysin
  • very useful for classifying streptococci
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7
Q

what is alpha haemolysis?

A

an indistinct zone of partial destruction of red blood cells (RBCs) appears around the colony, often accompanied by a greenish to brownish discolouration of the medium (opaque)

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8
Q

what are examples of alpha haemolytic organisms?

A
  • Streptococcus pneumoniae (can cause lobar pneumonia & meningitis) is alpha haemolytic
  • S. oralis
  • S. milleri
  • S. sanguis
  • many oral streptococci are alpha haemolytic
  • some alpha haemolytic species can cause serious pathology such as infective endocarditis - caused by viridans streptococci
  • S. intermedius is also alpha haemolytic
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9
Q

what is beta haemolysis?

A

a clear, colourless zone appears around the colonies, in which the red blood cells have undergone complete lysis

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10
Q

what are examples of beta haemolytic organisms?

A
  • Streptococci pyogenes, Streptococci agalactiae and many other streptococci are beta haemolytic
  • many other bacteria besides streptococci can be beta
    haemolytic including S. aureus and listeria monocytogenes
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11
Q

how can S. aureus be differentiated from other beta haemolytic organisms?

A

it’s important to differentiate staphylococcus aureus and this can be done by:
• looking at appearance on blood agar - will be creamy
yellow
• also will have a positive coagulase test

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12
Q

how can you differentiate between different beta haemolytic bacteria?

A

by using Lancefield grouping (detecting surface antigens)

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13
Q

what is Lancefield grouping?

A
  • used to differentiate between beta haemolytic bacteria
  • detects surface antigens
  • A, C, G = tonsillitis and skin infection
  • B = neonatal sepsis and meningitis
  • D = UTI/enterococci
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14
Q

what is gamma haemolyis?

A

no haemolysis of RBCs

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15
Q

what are examples of organisms showing gamma haemolysis?

A
  • enterococcus faecalis
  • Staphylococcus saprophyticus
  • Staphylococcus epidermidis
  • S. bovis
  • S. mutans
  • S. milleri
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16
Q

what is the optochin test?

A
  • place optochin soaked disc on agar and watch bacterial growth
  • test to differentiate between streptococcus pneumoniae (causes lobar pneumonia and meningitis - sensitive to optochin so will be a clear zone around the disc
  • Viridans streptococci (infective endocarditis) and other alpha haemolytic streptococci are resistant to it so there will be growth around the disc
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17
Q

what are results of the optochin test?

A

sensitive = Streptococci pneumoniae; clear zone of no growth around disc

resistant = Viridans streptococci; growth around disc

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18
Q

what is the oxidase test?

A
  • tests if micro-organism contains a cytochrome oxidase - an enzyme of the bacterial electron transport chain
  • all bacteria that are oxidase positive are aerobic
  • bacteria that are oxidase negative may be either aerobic or anaerobic
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19
Q

what are some oxidase positive bacteria?

A
  • P. aeruginosa
  • V. cholerae
  • Campylobacter e.g. C. jejuni
  • Helicobacter
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20
Q

what are the results of the oxidase test?

A
  • oxidase positive = blue - bacteria is aerobic e.g. V. cholerae
  • oxidase negative = no colour change - bacteria may be aerobic or anaerobic
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21
Q

what does MacConkey agar grow? what are its uses?

A
  • only grows Gram negative bacilli
  • good at differentiating between lactose-fermenting and non-lactose fermenting Gram negative bacilli such as enterobacteria (gut coliforms)
  • bile salts present on this agar inhibit Gram positive bacteria and inhibit the swarming of a Gram negative bacterium Proteus spp.
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22
Q

how does MacConkey agar show lactose/non-lactose fermenting bacteria?

A

has a pH indicator on it so bacteria that ferment lactose and thus produce acid will make the agar appear pink/red

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23
Q

what are some lactose fermenting bacteria that can be identified on MacConkey agar?

A
  • E. coli
  • Klebsiella pneumonia
  • Enterobacter spp.
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24
Q

what are some non-lactose fermenting bacteria that can be identified on MacConkey agar?

A
  • Salmonella spp.

- Shigella spp.

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25
what is the use of XLD agar?
used to differentiate Salmonella and Shigella mainly
26
what are the results of MacConkey agar?
- Gram negative bacilli only - will turn pink/red if lactose fermenting bacteria e.g. E. coli - will turn white/transparent if non-lactose fermenting e.g. Salmonella
27
what are the results of XLD agar?
Salmonella = red/pink colonies some with black spots Shigella = red/pink colonies
28
what are some Gram positive cocci?
- Staphylococci - Streptococci - Enterococci - anaerobic Streptococci e.g. peptostreptococci
29
what are some Gram negative cocci?
- Neisseria - Moraxella - anaerobic cocci e.g. Veillonella spp.
30
what are some Gram positive bacilli?
- Bacillus e.g. B. anthracis - Clostridia - Corynebacteria e.g. C. diptheriae - Listeria monocytogenes - anaerobic bacilli e.g. Clostridia - Propionibacteria
31
what are some Gram negative bacilli?
- E. coli - Campylobacter - Pseudomonas - Salmonella - Shigella - Proteus
32
give some examples of aerobic Gram positive cocci?
staphylococcus and streptococcus
33
give some examples of Staphylococcus?
S. aureus and S. epidermidis
34
give some examples of anaerobic Gram positive cocci?
peptostreptococcus
35
give some examples of anaerobic Gram negative bacilli?
Bacteroides (e.g. B. fragilis)
36
what are some examples of aerobic Gram negative bacilli?
- coliforms - pseudomonads - vibrio - parvobacteria
37
what areas of the body are sterile and non-sterile?
non-sterile: nasal cavity, larynx, stomach, colon sterile: lungs, gall bladder, kidneys, eye, CSF
38
what is the growth rate of bacteria?
- you measure bacterial growth by shining light on bacteria and measuring absorption - bacteria divide by binary fission - the growth lag is due to the fact the bacteria are taking in the nutrients needed to divide and grow - then there is exponential growth until the nutrient runs out - viable = death phase
39
what is transformation in bacteria?
the genetic alteration of a bacterial cell via the uptake of an exogenous substance e.g. via plasmid
40
what is transduction in bacteria?
process by which foreign DNA is introduced into a bacteria via vector or virus e.g. via a bacteriophage (virus)
41
what is conjugation in bacteria?
the transfer of genetic material between bacterial cells by direct cell-cell contact e.g. via sex pilus
42
what is the normal habitat of Staphylococcus? how many species are there?
- normal habitat is on the nose and skin - at least 40 species - can be coagulase positive (clumping) or negative (no clumping) - coagulase converts fibrinogen to fibrin i.e. clot - some bacteria produce it to protect against white blood cells e.g. S. aureus
43
what is the common clinical presentation of S. aureus?
- pain in shoulder - elevated temperature - MRI scan - disc injection and osteomyelitis (bone infection) C6 and C7 - blood cultures show staphylococcus aureus - treat with flucloxacillin (antibiotic) for 3 months - Staph. aureus is responsible for around 90% of osteomyelitis
44
how is S. aureus spread?
aerosol and touch e.g. coughing and breathing
45
what is MRSA resistant to?
* Beta-lactams antibiotics * gentamicin * erythromycin * tetracycline
46
what is the virulence/pathogenic factors of S. aureus?
- pore-forming toxins (some produce these) e.g: • PVL toxin which is prodcued by many MRSA strains and causes haemorrhagic pneumonia • alpha-haemolysin which can induce apoptosis (at low levels) or cause widespread necrosis (at high levels) - proteases e.g: • exfoliatin which causes scalded skin syndrome - toxic shock syndrome toxin (TSST) which stimulates cytokine release - protein A which is a surface protein which binds immunoglobulins in wrong orientation
47
what are the pore-forming toxins of S. aureus? what are their actions?
• PVL toxin which is prodcued by many MRSA strains and causes haemorrhagic pneumonia • alpha-haemolysin which can induce apoptosis (at low levels) or cause widespread necrosis (at high levels)
48
what are associated conditions of S. aureus?
- wound infections (staph. aureus is very good at colonising these) - abscesses - osteomyelitis - scalded skin syndrome - toxic shock syndrome - food poisoning
49
what are some coagulase negative bacteria?
S. epidermis and S. saprophyticus
50
what are features of S. epidermis?
- opportunistic infections in prosthetic limbs and catheters | - its main virulence factor is its ability to form persistent biofilms
51
what can S. saprophyticus cause?
acute cystitis
52
in what ways can streptococci be classified?
* haemolysis * Lancefield typing * biochemical properties
53
what is Lancefield typing?
a method of grouping catalase negative and coagulase negative bacteria based on the bacterial carbohydrate cell surface antigens
54
what are important groupings in Lancefield typing?
Group A - Strep. pyogenes | Group B - Strep. agalactiae; neonatal infections
55
what are some infections that are caused by Strep. pyogenes?
- wound infections such as cellulitis - tonsillitis and pharyngitis - otitis media - scarlet fever (caused by erythrogenic toxin)
56
what are complications of Strep. pyogenes?
- rheumatic fever - glomerulonephritis - some strains produce erythrogenic toxin which is responsible for scarlet fever, this toxin is a super-antigen meaning it gives rise to an exaggerated immunological response and increased circulating cytokine levels - infection with any strain of Strep pyogenes can give rise to complications that are immunologically mediated, so prompt treatment is required to reduce risks - assessment of risk can be estimated from the anti-streptolysin O titre
57
what can be used to assess risk for complications of Strep. pyogenes?
anti-streptolysin O titre
58
what are the secreted virulence/pathogenic factors of Strep. pyogenes?
* hyaluronidase - spreading * streptokinase - breaks down clots * C5a peptidase - reduces chemotaxis * streptolysins O & S toxin - binds cholesterol * erythrogenic toxin - exaggerated response
59
what is the action of hyaluronidase in Strep. pyogenes?
speading
60
what is the action of streptokinase in Strep. pyogenes?
breaks down clots
61
what is the action of C5a peptidase in Strep. pyogenes?
reduces chemotaxis
62
what is the action of streptolysins O and S toxin in Strep. pyogenes?
binds cholesterol
63
what is the action of erythrogenic toxin in Strep. pyogenes?
exaggerated response
64
what are surface virulence/pathogenic factors of Strep pyogenes?
* hyaluronic acid capsule - protection | * M protein - surface protein that encourages complement degradation
65
what is the action of hyaluronic acid capsule in Strep. pyogenes?
protection
66
what is the action of M protein in Strep. pyogenes?
surface protein that encourages complement degradation
67
what is the common presentation of Strep. pneumoniae?
- heavy smoker with nasal congestion and fever - 2 days later gets cough and severe chest pain - rust-coloured sputum - chest X-ray shows consolidation (lung filled with liquid) - blood and sputum culture show Strep. pneumoniae (draughtsman colonies)
68
what infections does Strep. pneumoniae cause?
- pneumonia - otitis media (middle ear infection) - sinusitis - meningitis
69
what are pre-disposing factors for Strep. pneumoniae?
- impaired mucus trapping e.g. viral infection - hypogammaglobulinemia - low levels of serum immunoglobulins which are required for efficient phagocytosis - asplenia - since spleen produces protein called tuftsin which acts to enhance phagocytosis so with no spleen then no tuftsin and this impairs phagocytosis and thus risk of infection - diabetes - renal disease - sickle cell disease - very young (younger than 2) since immune response to polysaccharide antigens is very poor
70
what are the virulence/pathogenic factors of Strep. pneumoniae?
- polysaccharide capsule (84 types) - is antiphagocytic - there is a polyvalent vaccine available for those under 2 but this only protects against 23/84 types - teichoic acid binds to choline receptors - peptidoglycan helps protect bacteria - pneumolysin cytotoxin is a pore-forming toxin
71
what is the action of the polysaccharide capsule in Strep. pneumoniae?
(84 types) - is antiphagocytic - there is a polyvalent vaccine available for those under 2 but this only protects against 23/84 types
72
what is the action of teichoic acid in Strep. pneumoniae?
binds to choline receptors
73
what is the action of peptidoglycan in Strep. pneumoniae?
helps protect bacteria
74
what is the action of pneumolysin cytotoxin in Strep. pneumoniae?
pore-forming toxin
75
what are viridans streptococci?
* collective name for oral streptococci * alpha or non-haemolytic * some cause dental caries and abscesses
76
what viridans streptococci cause infective endocarditis?
S. sanguis and S. oralis
77
what viridans streptococci are the most pathogenic?
most pathogenic are the milleri group: - S. intermedius - S. anginosis - S. constellatus - causing deep organ abscesses e.g. in brain & liver
78
what is the common presentation of Corynebacterium diphtheriae?
* child with severe sore throat * fever and malaise for 2 days * lymphadenopathy (swollen) in neck * rapid breathing * thick greyish membrane on tonsils
79
what does the swab show in Corynebacterium diptheriae?
gram positive rods/bacilli
80
what is the treatment of Corynebacterium diptheriae?
treated with anti-toxin (pre-formed antibody to toxin) and erythromycin (antibiotic helps remove symptoms and stop carriage and spread but does not destroy pathogen)
81
how is Corynebacterium diptheriae spread?
droplet spread
82
what is the virulence factor in Corynebacterium diptheriae?
caused by the production of a toxin which inhibits protein synthesis (inactivates elongation factor-2 in host cells by adding ADP-ribosyl group to aa dipthamide)
83
how can Corynebacterium diptheriae be prevented?
- prevention by vaccination with toxoid (inactivated toxin) - can grow in the presence of potassium tellurite - selective method for isolating this bacteria from throats of patients
84
what is LPS?
lipopolysaccharide is an endotoxin and forms the outer leaflet of the outer membrane of gram-negative bacteria and comprises: - Lipid A - the toxic portion of LPS that is anchored in the outer leaflet of the outer membrane - core (R) antigen - short chain of sugars, some are unique to LPS - somatic (O) antigen - a highly antigenic repeating chain of oligosaccharides
85
what is lipid A?
the toxic portion of LPS that is anchored in the outer leaflet of the outer membrane
86
what is the core (R) antigen?
short chain of sugars, some are unique to LPS
87
what is somatic (O) antigen?
a highly antigenic repeating chain of oligosaccharides
88
why do gram negative bacteria find secreting a toxin more difficult than gram positive bacteria?
the toxin/effector (protein) needs to travel past two membranes rather than just one
89
what are the cell surface antigens of gram negative bacteria?
- K antigen (EPS capsule) - H antigen (flagellum) - O (somatic) antigen (LPS)
90
what are examples of bacteria that do and don't have a H antigen?
- Shigella has no H antigen since it does not have flagellum | - Salmonella does have a H antigen since it does have a flagellum
91
what are features of Enterobacteria (coliforms)? what is used to differentiate between lactose fermenting and non-lactose fermenting forms?
- rods/bacilli - most are motile i.e. have flagella - some are intestinal parasites - are able to grow in anaerobic conditions - MacConkey agar is used to differentiate between lactose and non-lactose fermenting
92
what are features of Escherichia coli?
• commensals - most abundant facultative anaerobe (facultative means is able to i.e. is able to respire anaerobic, but not only anaerobically, can respire aerobically too) • they have flagella • there are many serotypes/strains • they all share a common ‘core’ genome
93
what are some infections that are caused by pathogenic E. coli strains?
- wound infections (surgical) - Urinary Tract Infections (UTIs) - also known as cystitis, 75%-80% female UTIs are from catheterisation - gastroenteritis in children and adults - travellers’ diarrhoea - bacteraemia - the presence of bacteria in the blood - meningitis in infants - rare in the UK
94
what are the differences between pathogenic and commensal E. coli?
* pathogenic E.coli contains blocks of genes that are not present in commensal E.coli (that live in the gut) * many pathogenic E.coli have ‘acquired’ pathogenicity from other bacteria by ‘mating’ and acquiring pathogenic blocks of genes
95
what is the virulence/pathogenicity factor for E. coli causing travellers diarrhoea? what is its mechanism of action?
- strain is called enterotoxigenic (ET) E.coli (ETEC) - has pilli which enable it to adhere to the tissue of the small intestine - when it binds to the tissue it releases a labile toxin that alters the role of the Gs protein on the GI cell surface meaning it can no longer stimulate adenyl cyclase resulting in more Cl- being released into the GI lumen - this results in water following, resulting in diarrhoea
96
what are the four species of Shigella?
- S. dysenteriae - S. flexneri - S. boydii - S. sonnei (commonest cause)
97
what is the action of the shigella species?
all four species cause damage to the intestinal mucosa that result in: - acute infection of the large intestine - painful diarrhoea often with blood and mucus in the stools
98
what is the infective dose of Shigella?
the infective dose is just 100 bacteria thus extremely easy to be infected
99
how is Shigella spread?
spread from person-to-person or via contaminated water or food
100
what are microfold (M) cells?
• these are found in the gut-associated lymphoid tissue (GALT) of the Peyer’s patches and in the mucosa- associated lymphoid tissue (MALT) • these cells initiate mucosal immunity responses and allow for the transport of microbes across the epithelial cell layer from the gut lumen where interactions with immune cells can take place
101
what is the pathogenesis of Shigella infection?
- bacteria are acid-tolerant so can survive and pass through the stomach - bacteria target microfold (M) cells - shigella induce their own uptake by M-cells, they then cross the epithelial cell layer where they are engulfed by macrophages - however, once engulfed they induce the apoptosis of the macrophages resulting in the release of damaging free radicals resulting in an inflammatory response and cell damage - eventually the bacteria will be destroyed by neutrophils
102
what toxin might Shigella release?
shiga toxin
103
what is the action of the shiga toxin released by Shigella?
some shigella bacteria also release a shiga toxin which disrupts protein synthesis resulting in necrosis: • this toxin targets the kidney resulting in haemolytic uraemic syndrome which can lead to death • shiga toxin is also produced by some E.coli e.g. EHEC
104
what are the two species of Salmonella?
- S.enterica - responsible for salmonellosis (any infection caused with salmonella) - S.bongori - rare, results from reptile contact
105
what are some infections caused by Salmonella?
- gastroenteritis - enteric fever; typhoid - bacteraemia
106
what are features of gastroenteritis caused by Salmonella?
* frequent cause of food poisoning from milk and poultry * 6-36 hour incubation * resolves in a week * localised infection
107
what are features of enteric fever caused by Salmonella?
* systemic disease * caused by Salmonella typhi and Salmonella paratyphi * spread is faecal-oral * results in fever, headache, dry cough * splenomegaly and hepatomegaly * diarrhoea may develop
108
what is the cause of enteric/typhoid fever?
Salmonella typhi and Salmonella paratyphi
109
what is the spread of enteric/typhoid fever?
faecal-oral
110
what are features of bacteraemia caused by Salmonella?
presence of bacteria in the blood - uncommon
111
what is the pathogenesis of salmonellosis?
- ingestion of contaminated food/water - has a high infective dose - need to ingest a significant amount for infection - Salmonella mediates its endocytosis across the gut lumen
112
what is the pathogenesis of gastroenteritis caused by Salmonella?
• bacteria presence results in chemokine release and neutrophil recruitment • this results in neutrophil-induced tissue injury due to the inflammatory response • there is fluid and electrolyte loss due to cell damage resulting in diarrhoea • eventual inflammation/necrosis of gut mucose
113
what is the pathogenesis of enteric fever caused by Salmonella?
• migrates to the basolateral membrane of cells in the intestinal lumen - Peyers patch where it results in inflammation and ulceration - diarrhoea • however, initially there is little damage to the gut mucosa • bacteria is then engulfed and survives then spreads systemically via the lymph nodes • then enters bloodstream via the thoracic duct and then multiplies in the macrophages of the liver, spleen and bone marrow resulting in septicaemia which results in massive fever • then spreads to the gall bladder from the liver where person can be in a carrier state from 1 year to the rest of their life
114
what are features of Klebsiella pneumoniae? what infections can it cause?
- opportunistic - causes different nosocomial (hospital acquired) infections: • pneumonia • bloodstream infections • wound or surgical site infections • meningitis
115
what are features of Vibrio cholerae?
- facultative anaerobe - curved rods/bacilli with single polar flagellum - results in cholera - the most severe diarrhoeal disease
116
how is Vibrio cholerae transmitted?
faecal-oral route - faecal contaminated water and uncooked shellfish
117
what is the infective dose of Vibrio cholerae?
high infective dose is required since its sensitive to acid i.e. acid in stomach - requires many to get past the stomach
118
what is the incubation period of Vibrio cholerae?
5 hours (multiplies in small intestine)
119
what is the clinical presentation of Vibrio cholerae?
- results in voluminous watery (rice-water) stools i.e. secretory diarrhoea - can lose 20 litre/day plus electrolytes, this results in: • dehydration and subsequent death • 60% mortality - there is no blood or fever since there is no invasion or damage to mucosa
120
what is the treatment of Virbio cholerae?
80% treated with oral rehydration
121
what are the virulence determinants of Vibrio cholerae?
* pilli - required for colonisation | * Cholera toxin - acts in same way as E.coli labile toxin
122
what is the action of the Cholera toxin in Vibrio cholerae?
- results in uncontrolled cyclic AMP production - which results in the activation of protein kinases - which causes the modification of ion transporter activity causing the loss of Cl- & Na+ resulting in massive H2O loss
123
what are features of Pseudomonas aeruginosa?
- motile - single polar flagellum - opportunistic (serious cause of nosocomial infections) - multiple antibiotic resistance
124
where can Pseudomonas aeruginosa cause localised acute infections?
- burn/surgical wounds - UTIs (catheters) - keratitis (inflammation of cornea)
125
where can Pseudomonas aeruginosa cause systemic (bacteraemic) acute infections?
neutropenic (low on neutrophils) patients (leukaemia, chemotherapy, AIDS)
126
what can Pseudomonas aeruginosa cause in ICU patients?
nosocomial pneumonia
127
what can Pseudomonas aeruginosa cause chronically?
cystic fibrosis
128
what is the effect of Pseudomonas aeruginosa on CF patients?
- have poor functioning Cl- transporters meaning they have dehydrated lung mucus which is the perfect environment for bacteria to grow - virtually impossible to remove pseudomonas in cystic fibrosis patient since antibiotic resistant
129
what are features of Haemophilus influenzae?
- exclusively human parasite - nasopharyngeal carriage in 25-80% population - fastidious (specific requirement for survival) - non-motile
130
where are Haemophilus influenzae infections mainly seen?
young children and adult smokers
131
what can Haemophilus influenzae cause in young children and adult smokers?
* important cause of meningitis, when it crosses the blood-brain barrier (less than 5yrs) and bronchopneumonia * epiglottitis, sinusitis, otitis media (ear infection) * bacteraemia * cystic fibrosis and COPD lung infections
132
how is Haemophilus influenzae fastidious?
- specific requirement for survival • will not grow on blood agar which supports growth of many other fastidious bacteria - since it cannot access haem in this form • will only grow on chocolate agar: - blood agar which has been heated to 80 degrees to allow the release of haem by red blood cells
133
what is chocolate agar?
blood agar which has been heated to 80 degrees to allow the release of haem by red blood cells
134
what are the virulence determinants of Haemophilus influenzae? what do each of them cause?
• pilli: adherence to epithelial cells and mucin • capsule: - commensals and respiratory tract pathogens are non-capsulate - invasive strains are capsulate (can penetrate the nasopharyngeal epithelium) • lipopolysaccharide (LPS) endotoxin - results in inflammation
135
what is Bordatella pertussis? how infectious is it?
* pertussis is whooping cough * short (sometimes oval) rods/bacilli * highly contagious with a low infect dose
136
what is the transmission of Bordatella pertussis?
aerosol transmission
137
what is the pathophysiology of Bordatella pertussis infection? what is the clinical presentation?
• adhere to the ciliated epithelia of the upper respiratory tract/trachea • non-specific flu-like symptoms followed by paroxysmal coughing (cough followed by inhalation resulting in whooping sound) • can lead to sub-conjunctival haemorrhage
138
what is Neisseria? where does it present?
• non-flagellated diplococci (go around in pairs) • present in polymorphonuclear lymphocytes of CSF or urethral discharge during infection
139
what are the two species of Neisseria?
N. meningitidis | N. gonorrhoeae
140
what are features of N. meningitidis? what is the transmission?
- present in the nasopharynx of 5-10% of the population (asymptomatic) - person-person aerosol transmission (university or barracks)
141
what is the pathogenesis of N. meningitidis infection?
crosses the nasopharyngeal epithelium and enters the bloodstream in a small proportion of colonised individuals: - asymptomatic bacteraemia (if low numbers of bacteria) or septicaemia if high - meningitis - the colonisation of the subarachnoid space after crossing the blood-brain barrier - there is a very high risk of mortality in the septicaemic form if not treated
142
what are the virulence determinants of N. meningitidis? what do they each do?
• capsule is major virulence determinant: - non-capsulated is only found in the nasopharynx - capsule is anti-phagocytic • pilli on bacteria promote colonisation and cell invasion • lipopolysaccharide results in cytokine cascade and inflammatory response which can lead to sepsis
143
what is the role of the capsule as a virulence determinant in N. meningitidis? where is the non-capsulated form found?
capsule is major virulence determinant: - non-capsulated is only found in the nasopharynx - capsule is anti-phagocytic
144
what is the role of pili as a virulence determinant in N. meningitidis?
pilli on bacteria promote colonisation and cell invasion
145
what is the role of LPS as a virulence determinant in N. meningitidis?
LPS results in cytokine cascade and inflammatory response which can lead to sepsis
146
what are features of N. gonorrhoea? how is it spread?
- not a commensal but can be asymptomatic (30% of infected females) - person to person only - non-capsulated unlike N.meningitis
147
what is the clinical presentation of N. gonorrhoea infection?
it's an STD resulting in: • urethritis with additional infection of female genitalia • can lead to infection of the fallopian tubes if infection ascends
148
what are types of Campylobacter?
C. jejuni and C. coli
149
what are features of Campylobacter?
``` • spiral rods/bacilli • most common cause of food poisoning in UK and US: - undercooked poultry e.g. BBQ - unpasteurised milk • has a low infective dose ```
150
what is the most common cause of food poisoning in the UK and US?
Campylobacter - undercooked poultry e.g. BBQ - unpasteurised milk
151
what is the clinical presentation of Campylobacter infection?
* results in mild-sever diarrhoea often with blood - usually self-limiting within a week * Campylobacter shed in faeces for around 3 weeks
152
what are the virulence factors of Campylobacter?
invasins and cytolethal distending toxin (CDT)
153
what is the role of invasins as a virulence factor of Campylobacter?
* invades ileal and colonic epithelial cells | * resulting in local acute inflammatory response i.e. tissue damage
154
what is the role of cytolethal distending toxin as a virulence factor of Campylobacter?
arrests the cell cycle meaning target cells swell and lyse
155
what are features of Helicobacter pylori?
* require CO2 (microaerophilic) | * spiral shaped
156
how much of the population does Helicobacter pylori affect?
present in 50% of global population but only a fraction will develop the disease
157
what diseases is Helicobacter pylori associated with?
* major role in gastritis and peptic ulcer disease | * implicated in gastric adenocarcinoma
158
what is the virulence factor of H. pylori? what does it do?
urease - hydrolyses urea to generate ammonia to act as a buffer to gastric acid
159
what are features of Chlamydia?
very small and non-motile
160
what are the two developmental stages in the growth cycle of Chlamydia?
- elementary bodies; dormant | - reticulate bodies; metabolically active and fragile
161
what are features of elementary bodies of Chlamydia?
- infectious - enter cell through endocytosis - prevent phagosome fusion - dormant
162
what are features of reticulate bodies of Chlamydia?
- replicative - non-infectious - metabolically active - fragile
163
what is the most common STD?
Chlamydia trachomatis
164
where can Chlamydia trachomatis spread to? is it symptomatic?
* can spread to the uterus and ovaries resulting in pelvic inflammatory disease * usually asymptomatic
165
what is the clinical presentation of Chlamydia trachomatis?
* can cause conjunctivitis (STD) | * can cause trachoma - blindness that is spread via flies
166
what are the most common sites/modes of infection caused by Gram-negative pathogens?
- respiratory tract - urinary tract - GI tract - meningitis - STIs - wound infections
167
what Gram-negative pathogens can infect the respiratory tract?
* Bordetella pertussis | * Haemophilus influenzae
168
what Gram-negative pathogens can infect the urinary tract?
* some E.coli strains | * Klebsiella pneumoniae
169
what Gram-negative pathogens can infect the GI tract?
* Vibrio cholera * Shigella dysenteriae * some E.coli strains * Campylobacter jejuni * Helicobacter pylori
170
what Gram-negative pathogens can cause meningitis?
* Neisseria meningitidis | * Haemophilus influenzae
171
what Gram-negative pathogens can cause STIs?
* Klebsiella pneumoniae | * Chlamydia trachomatis
172
what Gram-negative pathogens can cause wound infections?
* Pseudomonas aeruginosa | * some E.coli strains
173
what are features of fungi?
- eukaryotic - have a nuclear membrane - chitinous cell wall - heterotrophic: get nutrients from what they are living on - move by means of growth or spore release
174
what are yeasts?
type of fungi that is a small single celled organisms that divide by budding
175
what are moulds?
type of fungi that form multicellular hyphae and spores
176
what are dimorphic fungi?
some fungi exist as both yeasts and moulds switching between the two when conditions suit - these are dimorphic fungi
177
what is an example of a dimorphic fungi?
Coccidioides immitis
178
how does Coccidioides immitis act as a dimorphic fungi?
* grow as mould at ambient temperature | * convert to yeast form at body temperature after inhalation
179
what is the effect of fungi on humans?
- only a few fungal forms can actually infect humans - fungi have an inability to grow at 37 degrees (body temperature) - fungi also cannot evade the adaptive/innate immune response
180
what is the burden of fungal disease?
- enormous since most will have had at least one in lifetime e.g nappy rash, tinea pedis (athletes foot) and fungal asthma - however life-threatening fungal infection is rare in healthy hosts
181
what are invasive/life threatening fungal diseases in immunocompromised hosts?
* Candida line infections * Pneumocystis * invasive aspergillosis
182
what are invasive/life threatening fungal diseases in post-surgical patients?
intra-abdominal infections
183
what are invasive/life threatening fungal disease in healthy hosts?
- fungal asthma | - travel associated fungal infections e.g. dimorphic fungi
184
what is the aim of antimicrobial drug therapy?
to achieve inhibitory levels of the agent at the site of the infection without host cell toxicity
185
what does treating fungal disease rely on?
relies on identifying molecules with selective toxicity for organism targets
186
what is the target of fungal disease treatments?
* target does not exist in humans * target is significantly different to human analogue * drug is concentrated in organism cell with respect to humans * organism has an increased permeability to the compound * human cells are ‘rescued’ from toxicity by alternative metabolic pathways
187
why is selective toxicity harder to achieve for fungi?
in general the concept of selective toxicity is much harder to achieved for fungi as opposed to bacteria due to the fact that fungi are eukaryotic, and so are human cells thus they are more similar and thus harder to differentiate
188
what is the nucleus like in fungi? what are drugs that target this?
* DNA/RNA synthesis and protein synthesis * similar to mammalian * drugs targeting these: Flucytosine
189
what does the fungal cell wall contain? what are drugs that target this?
* mannoproteins * B1,3 glucan * B1,6 glucan * chitin * does not exist in humans * drugs targeting these: Echinocandins
190
what does the fungal plasma membrane contain? what are drugs that target this?
* containing ergosterol * human cell membrane contains cholesterol NOT ergosterol * drugs targeting these: Amphotericin, Azoles and Terbinafine
191
what is the equivalent to cholesterol in fungi?
ergosterol
192
what is an amphoteric compound?
a compound that is able to act as a base and an acid
193
what is an example of a polyene?
amphotericin B
194
what are polyenes? what are their mechanism of actions?
- drugs used to treat fungal infections - e.g. Amphotericin B - cause pore formation in ergosterol containing membranes - fungicidal
195
what is the affinity of amphotericin B for cholesterol in mammalian membranes?
it has 10 times lower affinity for cholesterol in mammalian | membranes
196
what toxicity can amphotericin B/polyenes cause?
- nephrotoxicity - dose dependent; usually reversible - distal renal tubular acidosis (hypokalaemia) - can cause hyperkalaemia if infused rapidly resulting in cellular damage - also causes infusion related; chills/rigors/hypotension and acute anaphylactoid reactions
197
what is the mechanism of action of allylamines?
* causes the reversible inhibition of squalene epoxidase (an enzyme required for growth of the fungi) * it's a fungicidal
198
what is an example of an allylamine?
Terbinafine
199
what is the metabolism of allylamines/terbafine? what are they primarily used against?
* it is well absorbed but undergoes extensive first pass metabolism resulting in a bioavailability of only 45% * distributes extensively to poorly perfused sites such as the skin and nail beds (common sites of fungal infection) * primarily used against Candida and Aspergillus
200
what are the side effects of allylamines/terbafine?
* well tolerated and only results in taste disturbance and deranged liver function tests (LFT) * it does result in increased CYP450 metabolism but this is by multiple enzymes and is minimally inhibitory
201
what is the mechanism of action of azoles?
* dose-dependent inhibitors of 14a-sterol demethylase - an important intermediate in the pathway of cholesterol (human) and ergosterol (fungi) production * it's a fungistatic
202
what azoles are active against different fungal infections?
• clotrimazole and ketoconazole is active against Candida • fluconazole is active against Cryptococcus • itraconazole is active against Aspergillus and dimorphics such as Coccidiodes and Sporothrix
203
what azoles work against Candida?
clotrimazole and ketoconazole
204
what azoles work against Cryptococcus?
fluconazole
205
what azoles work against Aspergillus and dimorphics e.g. Coccidiodes and Sporothrix?
itraconazole
206
what are adverse events caused by azoles?
- relatively safe - all associated with transaminitis (elevated transaminases in liver) and GI side effects - rare to cause severe hepatitis - alopecia with long term fluconazole - GI symptoms are more pronounced with itraconazole: • nausea, abdominal pain and diarrhoea • rare life threatening liver failure
207
what are drug interactions of fluconazole? how is it metabolised?
* hydrophilic and excreted unchanged | * less significant interactions with: warfarin, anxiolytics and calcineurin inhibitors
208
what are drug interactions of itraconazole? how is it metabolised?
``` • a potent CYP3A4 inhibitor • interactions with: - less significant interactions with: warfarin, anxiolytics and calcineurin inhibitors - steroids - statins ```
209
what are features of azole resistance? what drugs are most affected?
- multiple mechanism in Candida | - fluconazole and voriconazole most affected
210
what is the mechanism of action of echinocandins?
* inhibit 1,3 B glucan synthase - interferes with fungal cell wall synthesis * is fungicidal to susceptible yeasts * is fungistatic to moulds * has activity against mould but not yeast forms of dimorphics
211
what fungi are intrinsically resistant to echinocandins?
some fungi genera that do not have large amounts of 1,3 B glucan in their cell wall are intrinsically resistant to this drug class: - Crytococcus - Zygomycetes - Trichosporon - limited activity against Scedosporium
212
what is the bioavailability, penetration and drug interactions of echinocandins?
* has poor oral bioavailability thus IV only * has poor penetration into the CSF, eye and urine * few drug interactions
213
what drug toxicity can echinocandins cause?
- rare type-1 hypersensitivity - hepatotoxicity - hypokalaemia
214
what are the drug compounds, mechanism of action and uses of polyenes?
- Amphotericin B, Nystatin - binds to sterols and destabilises cell membrane - used in systemic and topical disease
215
what are the drug compounds, mechanism of action and uses of azoles?
- clotrimazole, miconazole, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole - inhibits ergosterol biosynthesis - used in topical and systemic disease
216
what are the drug compounds, mechanism of action and uses of allylamines?
- terbinafine - inhibit ergosterol biosynthesis - used in superficial infections, including onychomycosis
217
what are the drug compounds, mechanism of action and uses of echinocandins?
- caspofungin, anidulafungin, micafungin - inhibit the formation of cell wall glucan - used in systemic disease
218
what are the drug compounds, mechanism of action and uses of pyrimidines?
- 5-fluorocytosine - inhibit DNA and RNA synthesis - used in systemic disease
219
what are the drug compounds, mechanism of action and uses of grisan?
- griseofulvin - inhibits microtubule assembly - used in topical disease
220
how is Candida cultured?
- blood cultures are only half as sensitive for fungi as for bacteria - it's better to pick-up from tissue/fluids: • if cultured properly • if these samples can be obtained
221
what drugs are Candida sensitive to?
- pretty much all Candida are sensitive to Echinocandins | - pretty much all Candida are sensitive to Amphotericin B
222
what is 1,3 B-D glucan?
- the cell wall component of many fungi including common ascomycetous pathogens and pneumocystis - released into serum during invasive infection
223
what is onychomycosis?
fungal nail infection; very common
224
what is onychomycosis caused by?
- caused by dermatophyte moulds: • grow best at about 30 degrees - Trichophyton rubrum is the most common cause
225
what is the most specific test for onychomycosis?
microscopy is most specific, but 30% of the culture is negative
226
what are broad differential diagnoses of onychomycosis?
* psoriasis * lichen planus * trauma * eczema * malignant melanoma
227
what are the treatment options of onychomycosis? what are features of treatment?
- results of sampling can be confusing - limited treatment options: • topical amorolfine • systemic itraconazole or terbinafine - treatment takes ages - high failure rate with all therapies
228
what are features of Pneumocystis infection?
- infection/colonisation of health people is frequent and occurs early in life - disease develops only with moderate-severe immunocompromised especially in HIV, transplant and steroids - think pneumocystis when a patient has hypoxia that is more severe than the chest x-ray would suggest - especially with gradual onset or risk factors
229
what is treatment of Pneumocystis?
* Co-trimoxazole * Clindamycin * Pentamidine * Trimetrexate
230
what are the Mycobacteria of medical importance? what diseases do they each cause?
- M. tuberculosis; tuberculosis - M. leprae; leprosy - M.avium complex (MAC); disseminated infections in AIDS, infections in patients with chronic lung disease - M. kansasii - chronic lung infection - M. marinum - fish tank granuloma - M. ulcerans - Buruli ulcer
231
what organism causes TB?
Mycobacterium tuberculosis
232
what organism causes leprosy?
M. leprae
233
what organism causes disseminated infections in AIDS?
M. avium complex
234
what organism causes chronic lung infection?
M. kansasii
235
what organism causes fish tank granuloma?
M. marinum
236
what organism causes a Buruli ulcer?
M. ulcerans
237
what are microbiological features of Mycobacteria? what is its growth, spore formation, motility, cell wall content like?
- aerobic - have resistance to destaining by acid and alcohol - may cause meningitis - tuberculosis meningitis - can withstand phagolysosomal killing - non-spore formin - non-motile bacillus/rods - high cell wall content of high molecular weight lipids - slow growing - cell wall key components
238
are Mycobacteria aerobic or anaerobic?
aerobic
239
can Mycobacteria withstand phagolysosomal killing?
yes
240
what is the cell wall content of Mycobacteria? what are the key components of the cell wall?
* weakly gram-positive or colourless - it difficult to stain mycobacteria since they have a thick cell wall that doesn't take up stain easily * cell wall contains lipoarabinomannan * survives inside macrophages, even in low pH environments * mycolic acids and liporabinomannan - make up strong waxy cell wall that is hard for the immune system to target/damage
241
what is the growth of Mycobacteria? what does this mean for treatment?
* M. tuberculosis generation time 15-20 hours compared to 1 hour for common bacterial pathogens * slow growth means its difficult for antibiotics to target the division phase of the mycobacteria
242
what are Koch postulates?
- bacteria should be found in all people with disease - bacteria should be isolated from the infected lesions in people with the disease - a pure culture inoculated into a susceptible person should produce symptoms of the disease - the same bacteria should be isolated from the intentionally infected individual
243
what are features of acid-fast bacilli/rods? what makes it resistant to Gram stain?
- high lipid content with mycolic acids in cell wall makes Mycobacteria resistant to Gram stain - slightly curved, beaded bacilli/rods
244
what is the result of acid-fast bacilli on the Ziehl-Neelsen stain?
red/pink (positive for acid-fast)
245
how can nucleic acid be detected in Mycobacteria?
- nucleic acid amplification using PCR - produces rapid result for mycobacterium tuberculosis - highly sensitive and specific test - recommended for the rapid diagnosis in TB endemic countries
246
how are Mycobacteria processed in the body?
- Mycobacteria are acid fast bacilli that are phagocytosed by macrophages and are placed in a phagolysosome within the macrophage - the bacteria has adapted to the intracellular environment and aims to withstand phagolysosomal killing and escape to the cytosol - primarily through the presence of their thick waxy cell wall - the host aims to kill the mycobacterium using microbicidal molecules - acidification aids digestion and degradation by proteases of the mycobacteria which results in the generation of antigens for presentation to T-cells
247
what is the immunity of Mycobacterial infection?
- effective immunity requires CD4 T-cells which generate interferon gamma and this helps activate intracellular killing by macrophages - IL-12 release by macrophages further stimulates the generation of T helper cells and interferon gamma release - genetic defects in interferon gamma or IL-12 receptors or elements of their signalling pathways result in susceptibility to mycobacterial infection
248
what are features of granuloma in Mycobacterial infection?
granuloma are lesions the arise in a response that tries to contain mycobacteria (but also occur in other infections and non-infectious processes): • highly stimulated macrophages become epithelioid cells • some macrophages fuse with each other to form giant multinucleate cells “Langhans giant cells” • T cells including cytotoxic CD8 T-cells infiltrate the granuloma
249
how does a granuloma affect Mycobacteria?
a granuloma prevents nutrients from entering - thereby starving the mycobacteria: • TB will go into a dormant state when inside the granuloma • can reactivate at some point in the future when conditions are better
250
what is the response time of the immune system to Mycobacteria?
the highly immunogenic nature of mycobacterial lipids stimulate T-cell responses 3-9 weeks after exposure to M. tuberculosis
251
what are positive effects of the highly immunogenic nature of mycobacterial lipids?
macrophage killing of mycobacteria, containment of | infection, formation of a tissue granuloma
252
what are negative effects of the highly immunogenic nature of mycobacterial lipids?
hypersensitivity reactions (type 4) with skin lesions, eye lesions and swelling of joints
253
how can the reactivity of mycobacteria be measured?
- this reactivity can be measured in the tuberculin skin test where intradermal injection of purified protein derivatives induce skin swelling and redness - it can also be measured in interferon gamma release assays
254
how are interferon gamma release assays used to detect mycobacteria?
* use antigens specific to M. tuberculosis e.g. ESAT-60 and CFP10 to distinguish between this and BCG vaccine or environmental mycobacteria * IGRAs demonstrate exposure to M.tuberculosis but not active infection
255
what are principles of mycobacteria treatment?
- slowly replicating bacteria so need prolonged treatment - 6 months of antimicrobials - there are different populations of mycobacteria in particular locations intracellularly and extracellularly or in environments of differing pH - resistance may emerge on treatment so use multi-drug combinations to ensure target all populations and mutants - compliance is essential; directly observed treatment used for many patient groups to ensure success
256
what is the standard therapy for tuberculosis?
* Isoniazid (INH), Rifampicin (RIF), Pyrazinamide (PZA), Ethambutol (ETH) for two months * Isoniazid and rifampicin for further 4 months
257
what is given if resistance develops to anti-tuberculosis drugs?
* fluroquinolones * injectable agents such as; streptomycin, cyclosporine and capreomycin * prothionamide
258
what are the side effects of anti-tuberculosis drugs?
* hepatotoxicity - Isoniazid, rifampicin, pyrazinamide * peripheral neuropathy with isoniazid - give vitamin B6 to protect against this * optic neuritis - ethambutol
259
what is the pathophysiology of primary tuberculosis?
* bacilli settle in apex (top part near shoulders) and granuloma forms * bacilli taken in lymphatics to hilar lymph nodes * in apex of lungs there is more air and less blood supply thus fewer defending white cells to fight off infection
260
what is a primary complex of tuberculosis?
granuloma + lymphatics + lymph nodes
261
what is the pathophsyiology of latent tuberculosis?
* cell mediated immune (CMI) response from T-cells | * primary infection is contained but CMI persists
262
what is the clinical presentation and diagnosis of latent tuberculosis?
* no clinical disease (normal chest x-ray) | * detectable CMI to TB on tuberculin skin test of IGRA
263
what is the pathophysiology of pulmonary tuberculosis?
* could occur immediately following primary disease (post-primary) or after latent reactivation * cell mediated immune (CMI) response from T-cells * necrosis in lesion * caseous material coughed up leaving cavity * TB may spread in lung causing other lesions * CMI and caseation in lesion results in cavity
264
where do tuberculosis bacilli spread?
bacilli can spread from apex to hilar lymph nodes and then elsewhere
265
what can TB spread beyond the lungs cause?
- TB meningitis - miliary TB (widespread dissemination and tiny spotted lesions all over lungs and elsewhere) - pleural TB - bone and joint TB - genitourinary TB
266
what are the three groups of worms/helminths?
- nematodes (roundworms) - trematodes (flatworms, flukes) - cestodes (tapeworms)
267
what are types of nematodes (roundworms)?
* intestinal * Larva migrans * tissue (filaria)
268
what are types of trematodes (flatworms, flukes)?
* blood * liver * lung * intestinal
269
what are types of cestodes (tapeworms)?
* non-invasive | * invasive
270
what are features of helminths/worm-related diseases?
- rare in UK - most cases are imported - adult worms cannot usually reproduce without a period of development outside the body - worm cannot replicate inside body, so if it cannot get out it will eventually die - thus, although they usually produce innumerable larvae or eggs (which may themselves cause disease), the total worm burden cannot increase without constant re-exposure to infection
271
what is the pre-patent period in helminth disease?
the interval between infection and the appearance of eggs in the stool
272
what are protozoa?
* single-celled eukaryotic organisms with a definitive nucleus * eaten by invertebrates * important parasitic and symbiotic relationships
273
what is the main biological role of protozoa?
consumers of bacteria, algae and microfungi
274
how do protozoa eat food?
all eat food by phagocytosis and then digest it in intracellular vacuoles
275
in what environment do protozoa exist?
in aqueous environments and the soil
276
what are mastigophora (flagellates)?
- type of protozoa - flagellum as main locomotory organelle - usually reproduce by binary fission
277
what are examples of mastigophora?
- intestinal flagellates - haemoflagellates - other body sites
278
what is an example of an intestinal flagellate?
Giardia lamblia
279
what is the presentation of Giardia lamblia?
- 7-day business trip to Delhi 2 months ago - loose stools on last day of stay in India - ongoing offensive diarrhoea daily since return to UK - flatulence, abdominal cramps
280
what is an example of a haemoflagellate?
Trypanosoma spp.
281
what is the presentation of African Trypanosomiasis?
- also known as ‘sleeping sickness’ - bitten on arm by insect; lesion developed 2 weeks later > self-resolved - 2 years later he gets fever, lethargy and myalgia - excessive weight loss - personality change - irritability - increasing daytime tiredness - coma - the West African strain is more severe compared to the more endemic East African strain
282
what are sarcodina? how do they move?
- amoebae | - move by means of flowing cytoplasm and production of pseudopodia
283
what is an example of sarcodina?
Entanomoeba histolytica
284
what is the presentation of amoebiasis?
- 2-month visit to rural Botswana - bloody diarrhoea - on return to UK, increasing right upper quadrant pain - CT shows liver abscess
285
what are apicomplexa?
- sporozoans - no locomotory extensions - all species are parasitic - most are intracellular parasites - reproduce by multiple fission
286
what are examples of apicomplexa?
- malaria: Plasmodium spp. | - other: Cryptosporidium spp. and Toxoplasma gondii
287
what is the presentation of toxoplasmosis?
- recent HIV positive diagnosis: CD4 count: 70 (below 450 = low and below 100 = high risk of AIDs) - 2-week history of progressive left sided weakness - headaches and visual disturbances - commonly presents when people are immunosuppressed e.g. HIV/AIDs or cancer on chemotherapy
288
what are ciliophora?
- ciliates - very large group - have cilia that beat rhythmically at some stage in lifecycle - two types of nuclei (macronucleus and micronucleus)
289
what is an example of ciliophora? what does it cause?
Balantidium coli - presents mainly in those who are immunocompromised - causes severe diarrhoea and/or ulceration of colon
290
what are microsporidia? what can they cause?
* very small * production of resistant spores * causes diarrhoea in immunocompromised
291
what is an example of microsporidia?
Enterocytozoon bieneusi
292
what are some types of protozoa?
- mastigophora (flagellates) - sarcodina (ameobae) - apicomplexa (sporozoans) - ciliophora (ciliates) - microsporidia
293
what is malaria?
protozoan infection caused by Plasmodia spp..
294
what 4 species cause malaria?
``` 4 species cause human disease: • P. falciparum (most common) • P. ovale • P. vivax • P. malariae ```
295
how is malaria transmitted?
transmitted by the bite of the female anopheles mosquito
296
what is the epidemiology of malaria?
* 300-500 million cases per year (80% Africa) * 700,000 - 2.7 million deaths a year (more than 90% African) * cause of 50% of fever in African children under 5 * 50% of world population at risk
297
what causes the increasing incidence of malaria?
- increasing resistance of parasite to antimalarials - increased resistance of mosquito to insecticides - ecological and climate changes - means mosquitoes can be found in more countries - increased travel to endemic areas
298
what is the vector of malaria?
female anopheles mosquito; mainly bites at night
299
what is the distribution of the female anopheles mosquito?
worldwide distribution
300
when is infection of malaria acquired by the female anopheles mosquito?
* infection is acquired during feeding from infected human | * mosquito is infected for life
301
what is the lifespan of the female anopheles mosquito?
3-4 weeks
302
when/where does the female anopheles mosquito bite?
* night biting * mainly bites indoors * lifecycle depends on water
303
what are features of the protozoon of malaria? how does it cause different clinical manifestations?
* plasmodia lifecycle has stages in human and mosquito host | * variation in lifecycle between different Plasmodia spp. results in different clinical manifestations
304
when does the female anophales mosquito become infected with P. vivax?
the female anopheles mosquito becomes infected after taking a blood meal containing gametocytes, the sexual form of the malarial parasite
305
what occurs in the developmental cycle of malaria in the mosquito? how long does this last?
the developmental cycle in the mosquito usually takes 7-20 days (depending on temperature) culminating in the migration of infective sporozoites to the insect’s salivary glands
306
what are the stages of malaria infection?
1. infection of parasite (female anophales mosquito) 2. multiplication in liver 3. invasion and multiplication in RBCs 4. formation of gametocytes 5. completion of gametogony 6. migration of sporozoites to mosquito salivary gland
307
what happens to the sporozoites in the body?
* the sporozoites are inoculated into a new human host and those not destroyed by the immune system are rapidly taken up by the liver * here they multiply inside hepatocytes as merozoites; this is the pre-erythrocytic (or hepatic) sporogeny
308
what happens in pre-erythrocytic sporogeny?
* the sporozoites are inoculated into a new human host and those not destroyed by the immune system are rapidly taken up by the liver * here they multiply inside hepatocytes as merozoites; this is the pre-erythrocytic (or hepatic) sporogeny
309
what happens after a few days to the infected hepatocytes in malaria?
after a few days, the infected hepatocytes rupture, releasing merozoites into the blood, from where they are rapidly taken up by erythrocytes
310
what are hypnozoites? what parasites can become like this?
* in the case of P. vivax and P. ovale, a few parasites remain dormant in the liver as hypnozoites - these may reactivate at any time subsequently, causing relapsing infection - this is why its important to ask a 2 year travel history to counter P.vivax and P.ovale * can remember by OVO - Ovale Vivax Overstay * also note due to the dormancy the hypnozoites will not be eradicated by conventional antimalarials
311
what is OVO in relation to malaria?
Ovale Vivax Overstay - these parasites can become hypnozoites and remain dormant in the liver - won't be eradicated by conventional antimalarials
312
what happens in the RBCs in malaria?
• inside the red cells, the parasites again multiply, changing from merozoites to trophozoites to schizonts and finally appearing as 8-24 new merozoites • the erythrocyte ruptures, releasing the merozoites to infect further cells this is erythrocytic schizogony
313
what is erythrocytic schizogony?
• inside the red cells, the parasites again multiply, changing from merozoites to trophozoites to schizonts and finally appearing as 8-24 new merozoites • the erythrocyte ruptures, releasing the merozoites to infect further cells
314
how long does erythrocytic schizogony take in the different malaria parasites?
* each cycle of this process, which is called erythrocytic schizogony, takes about 48 hours in P. falciparum, P. vivax and P.ovale disease * whereas in P. malariae it takes 72 hours
315
what cells do P. vivax and P. ovale attack?
mainly reticulocytes and young erythrocytes
316
what cells does P. malariae attack?
tends to attack older cells
317
what cells does P. falciparum attack?
parasitises any stage of erythrocyte
318
what can merozoites develop into?
trophozoites or gametocytes
319
what are gametocytes?
- develop from merozoites | - not released from red cells until they are taken up by a feeding mosquito to complete the life cycle
320
what are the stages of malaria parasite?
sporozoites -> merozoites -> trophozoites -> schizonts -> merozoites
321
what is pathology of malaria related to?
pathology is related to anaemia, cytokine release and in the case of P. falciparum, widespread organ damage due to impaired microcirculation
322
what is the anaemia in malaria due to?
- haemolysis of infected red cells - haemolysis of non-infected red cells (Blackwater fever - when malaria is left to go untreated; results in dark coloured urine) - splenomegaly - folate depletion
323
what is the pathophysiology of P. falciparum malaria?
- red cells contains schizonts adhere to the lining of capillaries in the brain, kidneys, gut, liver and other organs - as well as causing mechanical obstruction, these schizonts can rupture, releasing toxins and stimulating further cytokine release
324
what is the normal incubation period of malaria?
10-21 days
325
what clinical features are common to all 4 species?
``` • very varied • fever is common (but not always present) • other common features: - chills and sweats - headache - myalgia - fatigue - nausea and vomiting - diarrhoea ```
326
when should malaria be considered?
in any febrile individual who has resided in or travelled to an endemic area
327
what are clinical features of P. vivax or P. ovale infection?
- illness is usually relatively mild - although P. vivax can occasionally cause severe disease - anaemia develops slowly and there may be tender hepatosplenomegaly - spontaneous recovery usually occurs within 2-6 weeks but hypnozoites in the liver can cause relapses for many years after infection - repeated infections often cause chronic ill health due to anaemia and hyper-reactive splenomegaly
328
what are clinical features of P. malariae infection? what is it associated with in children?
- this causes a relatively mild illness but tends to run a more chronic course - parasitaemia (parasites in blood) may persist for years, with or without symptoms - in children, P.malariae infection is associated with glomerulonephritis and nephrotic syndrome
329
what are the majority of deaths from malaria due to?
P. falciparum
330
what are clinical features of P. falciparum infection?
- causes a self-limiting illness similar to the other types of malaria - it may cause serious complications and the vast majority of deaths are due to P. falciparum - patients can deteriorate rapidly, and children in particular progress from reasonable health to coma and death within hours - a high parasitaemia (more than 1% of red cells infected) is an indicator of severe disease - cerebral - blackwater fever
331
what are general clinical features of malaria?
- shock | - hypotensive (<80 systolic and Gram-negative septicaemia)
332
what are metabolic clinical features of malaria?
- hypoglycaemia (<2mmol/L) | - metabolic acidosis
333
what are CNS features of malaria?
- prostration | - cerebral malaria
334
what are clinical features of malaria in the eyes?
retinal haemorrhages
335
what are respiratory features of malaria?
- tachypnoea | - acute respiratory distress syndrome
336
what are blood features of malaria?
- severe anaemia (haemolysis and dyserythropoiesis) - DIC - bleeding
337
what are renal features of malaria?
- haemoglobuinuria - oliguria - uraemia
338
what are GI features of malaria?
- diarrhoea - jaundice - splenic rupture
339
what is cerebral malaria marked by? what causes it?
``` - cerebral malaria is marked by diminished consciousness, confusion and convulsions progressing to coma and death - due to the reduced brain perfusion caused by schizonts adhering to the endothelial cells of capillaries = hypoxia to brain ```
340
what causes blackwater fever in malaria?
widespread intravascular haemolysis, affecting both parasitised and unparasitised red cells, giving rise to dark urine
341
what are clinical features of P. falciparum malaria in adults?
* coma * acute respiratory distress syndrome (ARDS) * anaemia * jaundice * hepatosplenomegaly * hypoglycaemia - since parasites eat up glucose (pregnant women especially susceptible) * blackwater fever * renal failure due to hypovolaemia and microvascular blockade due to the schizonts * shock secondary to bacterial sepsis
342
what are clinical features of P. falciparum malaria?
* non-specific; they stop crying, playing and eating * tachypnoea - rapid breathing * anaemia * hypoglycaemia * cerebral malaria * raised intracranial pressure * convulsions (60-80%) * rule out meningitis
343
what are non-specific features of malaria?
- anaemia - low platelets - hyperbilirubinaemia - mildly raised transaminases (ALT, AST)
344
how can films be used to detect malaria?
- thick and thin | - do films at least 12hrs apart to check for presence
345
what is seen on the thick film for malaria?
• sensitive but low resolution (difficult to interpret and speciate the parasite but has a higher yield) • tells you is malaria is present
346
what is seen on the thin film for malaria?
• can identify morphological features and quantification of parasitaemia • tells you type and parasite count, above 2% = severe • trophozoite most commonly used
347
how many films should be done before declaring malaria unlikely?
3 separate films should be examined before malaria is declared unlikely
348
what are features of complicated falciparum malaria?
- extreme weakness (e.g. inability to walk or sit) - impaired consciousness - hypoglycaemia - parasite count greater than 2% - spontaneous bleeding/disseminated intravascular coagulation - haemoglobinuria - renal impairment or electrolyte/acid-base disturbance (pH less than 7.3) - pulmonary oedema or adult respiratory distress syndrome - shock
349
what is treatment for complicated falciparum malaria?
* IV artesunate (gold standard) | * or IV quinine (second best since it causes hypoglycaemia so monitor sugar levels)
350
what is treatment of uncomplicated falciparum malaria?
- oral riamet - or oral quinine - add doxycycline as 2nd agent to treat undiscovered/untreated malaria
351
what is the treatment of non-falciparum malaria?
oral chloroquine
352
what is the treatment of P. vivax and P. ovale malaria?
- primaquine for hypnozoite clearance | - check G6PD (G6PD deficiency) and pregnancy status since not suitable for these individuals
353
how is malaria identified?
* most common imported tropical disease in UK * around 75% are falciparum * mixed infections * commonly presents ‘atypically’ e.g no fever * in pregnancy is severe
354
what is genetic immunity against malaria?
- sickle cell trait gives protection against malaria - Glucose-6-phosphate dehydrogenase deficiency (G6PD) - G6PD is an enzyme that is essential for assuring the normal lifespan for red blood cells, deficiency results in the sudden destruction of red blood cells and can lead to haemolytic anaemia - malaria parasites cannot survive in these red cells - Thalaessaemias confer protection against malaria
355
what is acquired immunity against malaria?
- recurrent infection can result in semi-immunity but this is lost if not reinfected after a couple of years - maternal transmission of antibodies across the placenta, but this diminishes over time
356
what are some vector borne diseases?
- dengue and viruses - malaria and protozoa - trypanosomes and leishmaniasis - helminths/worms
357
what are some soil/water borne diseases?
- hookworm, ascaris | - Buruli Ulcer
358
what are some faecal-oral diseases?
- amoebae, giardia | - typhoid, bacteria
359
what is the epidemiology of dengue fever?
- the most common arthropod-borne viral infection in humans; over 100 million cases occur every year in the tropics, with over 10,000 deaths from dengue haemorrhagic fever - disease is endemic in all tropical regions including norther Australia, most South-east Asian countries, tropical Africa and the Middle East and Caribbean countries - cases of dengue are also imported into the continental USA and Europe (e.g. Italy) via tourists returning from endemic countries
360
what is the most common arthropod-borne viral infection in humans?
dengue fever
361
what is dengue fever caused by?
flavovirus
362
what is dengue fever transmitted by?
transmitted by the Aedes mosquito which is daytime-biting - breeds in standing water in refuse dumps in inner cities
363
how long are humans and mosquitos infective for with dengue fever?
- humans are infective during the first 3 days of illness - mosquitoes become infective about 2 weeks after feeding on an infected individual and remain so for life
364
what is the incubation period of dengue fever?
incubation is 5-6 days following the mosquito bite
365
what is there an abrupt onset of in classical dengue fever?
* fever * malaise * headache * facial flushing * retrobulbar pain (behind eyes) * severe backache
366
what are clinical features of classical dengue fever?
- fever subsides after 3-4 days, the temperature returns to normal for a couple of days and then the fever RETURNS, together with the above features but milder - severe fatigue, a feeling of being unwell and depression are common several weeks after the fever has subsided
367
what is dengue haemorrhagic fever?
a severe form of dengue fever and believed to be the result of two or more sequential infections with different dengue serotypes
368
what is dengue haemorrhagic fever characterised by?
* capillary leak syndrome * thrombocytopenia (low platelet count) * haemorrhage * hypotension * shock
369
who does dengue haemorrhagic fever typically affect?
characteristically a disease of children, occurring most | commonly in South-east Asia
370
what are the initial clinical features of dengue haemorrhagic fever?
mild start, often with symptoms of an upper respiratory tract infection
371
what is there an abrupt onset of in dengue haemorrhagic fever?
* shock * haemorrhage into the skin and ear * bleeding from nose (epistaxis) * haematemesis (vomiting blood) * meleana (bloody stools) * all collectively known as dengue shock syndrome
372
what is the mortality of dengue haemorrhagic fever?
44%
373
what is the diagnosis of dengue fever?
* isolation of dengue virus by tissue culture, or detection of viral RNA by PCR in sera obtained during the first few days of illness - diagnostic * detection of virus-specific IgM antibodies, or of rising IgG titres in sequential serum samples
374
what is the management of dengue fever?
* supportive with analgesics and adequate fluid replacement | * in DHF, blood transfusion may be necessary as well as intensive care support
375
what is the size range of viruses?
* about 20-220nm diameter * only visualised by electron microscopy * in comparison staphylococci bacteria are about 1 micrometer in diameter
376
where do viruses grow?
grow only inside living cells
377
where should samples for testing for viral infections come from?
when diagnosing viral infections samples do not need to come from sterile sites since there are no commensal viruses to confuse with
378
what kind of nucleic acid do viruses have?
posses only one type of nucleic acid, RNA or DNA
379
what is the structure of viruses?
- posses only one type of nucleic acid, RNA or DNA - no cell wall structure but have an outer protein coat surrounded in some viruses by a lipid envelope (contains viral proteins and lipids) - essentially inert outside the host cell, but carry proteins that function as enzymes inside the cell - proteins on virus surface allow attachment to complementary receptors on susceptible host cell plasma membrane
380
what do viruses do once inside the cell?
takeover protein manufacture in order to replicate itself
381
what are the stages of virus replication?
1. attachment 2. cell entry 3. interaction with host cells 4. replication 5. assembly 6. release
382
how do viruses attach to host cells?
viral and cell receptors e.g. HIV (gp120 on HIV and CD4 on T cell)
383
how do viruses enter the host cells? what parts of it enter and what parts don't?
- only the viral ‘core’ which carries the nucleic acid and some associated proteins acting as enzymes for replication and negation of intracellular host defence factors are freed into the host cell cytoplasm - outer protein coat does not enter
384
how do viruses interact with host cells?
- virus uses cell materials (enzymes, amino acids, nucleotides) for their own replication - also need to subvert host cell defences
385
how do viruses replicate within host cells?
production of progeny viral nucleic acid and viral proteins in nucleus, cytoplasm or both
386
how do viruses assembly within host cells?
- can occur in nucleus e.g. herpesvirus - can occur in cytoplasm e.g. polio virus - can occur in cell membrane e.g. influenza virus
387
how do viruses get released from host cells?
- by bursting open (lysis) of cell e.g. rhinovirus - by ‘leaking’ (exocytosis) from the cell overtime e.g. HIV & influenza virus (2-3 days from upper respiratory tract) - only a few virus particles will enter the host but millions will exit due to replication
388
how do viruses cause disease?
- in most viral disease, more than one damage-inducing mechanism operates - some host-derived immunopathological damage occurs in most visual infections
389
what are the mechanisms of viral disease?
1. damage by direct destruction of host cells e.g. polio, influenza (respiratory cells) and HIV (immune cells 2. damage by modification of host cell structure or function 3. damage involving over-reactivity of the host as a response to infection - immunopathological damage e.g. hep B and C and HIV 4. damage through cell proliferation and cell immortalisation (cancer) e.g. human papillomavirus (HPVs): 5. evasion of both extracellular and intracellular host defences
390
what are examples of viruses that cause damage by direct destruction of host cells?
- polio virus - influenza (respiratory cells) - HIV (immune cells)
391
how does polio virus cause disease?
- 3 types but type 1 is the most severe - controlled by vaccination, enters body orally then invades and replicates in the gut then travels in the bloodstream and targets the brain where it results in direct brain cell destruction - once infection reaches the brain in unimmunised person it's very difficult to deal with and can result in paralysis - by the time an immune response is in effect, the virus has already caused damage
392
what are types of damage by modification of host cell structure or function by viruses? what are examples of organisms for each type?
* physical modification e.g. rotavirus or HIV | * functional modification e.g. rotavirus, respiratory syncytial virus (RSV) and HIV
393
what viruses cause disease by physical modification of the host cell?
rotavirus or HIV
394
what viruses cause disease by functional modification of the host cell?
rotavirus, respiratory syncytial virus and HIV
395
what is the pathogenesis of rotavirus infection? what are histological features and clinical presentations?
1. following ingestion, rotavirus infects epithelial cells of the small intestine, mainly in the jejunum (rotavirus are resistant to acid pH) 2. histologically, there is shortening and atrophy of the villi, flattening of the epithelial cells and stripping of the microvilli - decreasing the surface areas of the small intestine 3. this limits the production of digestive enzymes such as the disaccharides, normally synthesised by the cells of the brush border 4. the patient suffers a malabsorptive state in which dietary nutrients such as sugars are not absorbed by the small intestine 5. this results in hyperosmotic effects causing profuse diarrhoea
396
what is the treatment of rotavirus infection?
- fluid replacement therapy can usually solve the problem - if caught early its easily treatable - if caught late there good by some long term problems
397
what viruses cause disease via over-reactivity of the host as a response to infection?
hep B and C, and HIV
398
what are features of HBV?
- the majority of HBV infection are asymptomatic - both HBV and hepatitis C are spread by blood or sexual contact - following symptomatic HBV infection there are massive antibody and cell mediated immune (CMI) responses that destroy many virally infected hepatocytes - this results in extensive liver damage resulting in jaundice - during acute infection, large numbers of infectious HBV particles are produced - if you recover (most do) then you will be a carrier and 80% will be asymptomatic
399
how are hep B and C spread?
blood or sexual contact
400
what is a chronic carrier state in HBV?
in a HBV carrier there is a steady-state between virus | replication in host cells and the host defence responses
401
what is there in the steady-state in HBV carrier state?
- limited but sustained viral replication - natural hepatocyte regeneration - proliferation of hepatocytes due to the oncogenic properties of HBV - liver cell destruction by CD8+ T cells that recognise HBV proteins on the hepatocyte surface as ‘foreign’ - no clinical symptoms but HBV particles circulate in the patients bloodstream
402
what can HPV cause?
- causes plantar warts | - can result in cancers, particularly those of the cervix
403
what is the structure and type of HPV?
- has no envelope compared to influenza, hepatitis B or C - very small - there are 70-80 different viruses, only type 16 and 18 have oncogenic potential in humans
404
what types of HPV have oncogenic potential in humans?
16 and 18
405
what is cervical carcinoma caused by?
* HPV 16 and 18 are responsible for cervical carcinoma | * result of HPV infection of supra basal layer in genital tract
406
how does HPV replicate in the body and cause cervical carcinoma?
• once in the supra basal layer, the virus may partially replicate including transcription and expression of several early viral gene products • at some point the HPV genome may become integrated into the host cell chromosome • following integration, control of viral gene expression by the HPV E2 protein is lost and the HPV E6 and E7 proteins may be expressed • when expressed, the HPV E6 and E7 proteins prevent the operation of two cell growth and proliferation suppressor proteins - Retinoblastoma (Rb) and p53 • excessive cell growth and proliferation occurs and cervical cell carcinoma can result
407
what proteins and signalling cascades are involved in cervical carcinoma caused by HPV?
• following integration, control of viral gene expression by the HPV E2 protein is lost and the HPV E6 and E7 proteins may be expressed • when expressed, the HPV E6 and E7 proteins prevent the operation of two cell growth and proliferation suppressor proteins - Retinoblastoma (Rb) and p53
408
what are methods of evasion of both extracellular and intracellular host defences by viruses?
- virus persistence - virus variability - variation of antigens - persistence or latency - cell to cell spread - antigenic variability - prevention of host cell apoptosis - down regulation of interferon and other intracellular host defence proteins; most viruses do this - interference with host cell antigen processing pathways
409
what are examples of viruses that cause disease by evading host defences by virus persistence?
- Herpes viruses (survive throughout lifetime) - Hepatitis B and C viruses - measles virus - HIV
410
what are examples of viruses that cause disease by evading host defences by virus variability?
- influenza (mutates yearly - a vaccine that works one year will be less effective the next year) - HIV - Hepatitis C virus - rhinovirus
411
what are mechanisms for viral evasion of host defences at the cellular level?
- persistence or latency | - cell to cell spread
412
what are examples of viruses that cause disease by evading host defences by persistence or latency?
- all herpes viruses (HSV- 1 and 2) - Varicella-zoster virus (VZV) - Epstein-barr virus (EBV) - causes glandular fever, remains latent in B cells meaning you carry virus for rest of life and can transmit via oral secretions
413
what are examples of viruses that cause disease by evading host defences by cell to cell spread?
- measles virus | - HIV
414
what are examples of viruses that cause disease by evading host defences by antigenic variability?
- influenza type A virus - HIV - Rhinovirus
415
what are examples of viruses that cause disease by evading host defences by prevention of host cell apoptosis?
- Herpes virus - HIV - since host cell defence mechanism is to destroy itself, the virus releases proteins to prevent this and is thus able to continue to replicate
416
what are examples of viruses that cause disease by evading host defences by interference with host cell antigen processing pathways?
- Herpes virus - Measles virus - HIV
417
what are examples of viruses varying their antigens to evade host defence?
- variation through the formation of ‘quasi-species’ e.g. HIV and hepatitis C virus - variation through gene re-assortment and mutation e.g. Influenza A viruses and HIV - variation through many stable serotypes e.g. rhinoviruses - about 110 different cold viruses
418
what is the single most effective method of preventing cross infection?
hand hygiene!
419
what are CPEs?
- Carbapenemase producing Enterobacteriaceae | - also known as coliforms - standard gut germs
420
what are some examples of coliforms/CPEs?
* E.coli * Klebsiella * Serratia * Enterobacter
421
what can coliforms/CPEs cause?
- colonisers of the large bowel, skin below waist and moist sites - the most common causes of UTI and intra-abdominal infection - occasional respiratory tract infection and skin and soft tissue infection - in the past, the vast majority of these germs were susceptible to the antibiotics that we currently use with gram negative infection
422
what are carbapenems?
these are the broadest spectrum beta-lactam antibiotics available
423
how are carbapenems used?
they have moved from being rarely used last resort antibiotics to frequently used second-line agents and even first-line therapy for patients with severe sepsis; this is because resistance of gram negatives to other agents like cephalosporins and piperacillin-tazobactam has increased
424
what is the action of carbapenems?
- hydrolyse carbapenems and other beta-lactams | - confer resistance to the entire class of antibiotic
425
what are antimicrobials?
agents produced by micro-organisms that kill or inhibit the growth of other micro-organisms in high-dilution
426
what was the first antibiotic?
penicillin
427
what are most used antimicrobials now like?
semi-synthetic derivatives of antimicrobials
428
how do antibiotics work?
antibiotics are molecules that work by binding a target site on a bacteria: - defined as points of biochemical reaction crucial to the survival of the bacterium - the crucial binding site will vary with the antimicrobial class
429
what is a target site for antibiotics?
defined as points of biochemical reaction crucial to the survival of the bacterium
430
what are types of antibiotics?
- Beta lactams (penicillins and cephalosporins) glycopeptides - Metronidazole and Rifampicin - Fluroquinolones - Aminoglycosides, Tetracyclines, Macrolides and Chloramphenicol - Sulphonamides and Trimethoprim
431
what are the targets of beta lactam antibiotics?
these bind to bacterial cell wall and result in the inhibition of cell wall synthesis e.g. penicillin binding proteins on bacteria surface
432
what are the targets of metronidazole and rifampicin antibiotics?
interfere with nucleic acid synthesis or function
433
what are the targets of fluroquinolone antibiotics?
inhibit DNA gyrase (essential for bacterial DNA replication)
434
what are the targets of aminoglycosides, tetracyclines, macrolides and chloramphenicol?
inhibit ribosomal activity and protein synthesis
435
what are the targets of sulphonamides and trimethoprim?
inhibit folate synthesis - required for bacteria to grow since folic acid cannot cross the bacteria cell wall
436
what are some antibiotics that target the bacterial cell wall?
beta lactams (penicillins and cephalosporins) glycopeptides
437
what are some antibiotics that interfere with nucleic acid synthesis/function?
metronidazole and rifampicin
438
what are some antibiotics that inhibit DNA gyrase?
fluroquinolones
439
what are some antibiotics that inhibit ribosomal activity and protein synthesis?
aminoglycosides, tetracyclines, macrolides and chloramphenicol
440
what are some antibiotics that inhibit folate synthesis?
sulphonamides and trimethoprim
441
what are features of bacteriostatic antibiotics?
* prevent the growth of bacteria but not necessarily kill it * however in more than 90% they kill in 18-24 hours * antibiotics that inhibit protein synthesis, DNA replication or metabolism are bacteriostatic
442
what are features of bactericidal antibiotics?
* these agents kill the bacteria * they kill more than 99% in 18-24 hours * antibiotics that generally inhibit cell wall synthesis * useful if there is poor penetration e.g. endocarditis or difficult to treat infections or need to eradicate infection quickly e.g. meningitis
443
what must an antibiotic do to be effective?
- the drug must not only attach to its binding target but also must occupy an adequate number of binding sites, which is related to its concentration within the microorganism - to work effectively, the antimicrobial should remain at the binding site for a sufficient period of time in order for the metabolic processes of the bacteria to be sufficiently inhibited - must reach and stay at the site of bacterial infection
444
what are the two major determinants of antibacterial effects?
concentration and the time that the antimicrobial remains on the binding sites
445
what is concentration dependent killing? what is the key parameter?
* the ‘knockout punch’ | * key parameter is how high the concentration is above the MIC
446
what are examples of antibiotics that use concentration dependent killing?
- aminoglycosides | - quinolones
447
what is time dependent killing? what is the key parameter?
* sustained killing | * key parameter is the time that serum concentrations remain above the MIC during the dosing interval
448
what are examples of antibiotics that use time dependent killing?
- beta-lactams (penicillins, cephalosporins, carbapenems, monobactams) - clindamycin - macrolides (erythromycin, darithromeycin) - oxazolidinones (linezolid)
449
how does the antimicrobial reach and stay at the site of bacterial infection?
pharmokinetics - movement of a drug from its administration site to the place of its pharmacologic activity and its elimination from the body: - release from the dosage form - absorption from the site of administration into the bloodstream - distribution to various parts of the body, including the site of action - rate of elimination from the body via metabolism (liver) or excretion (kidney) of unchanged drug
450
what are considerations when administering antibiotics?
- site of infection | - what antibiotics are safe for the patient
451
how can the site of infection be considered when administering antibiotics?
* which antibiotics will penetrate that site? * what is the pH of the site? * is the antibiotics lipid soluble?
452
how can the safety of antibiotics be considered when administering them?
* intolerance, allergy and anaphylaxis * side effects * age * renal and liver function * pregnancy and breast feeding * drug interactions * risk of clostridium difficile (antibiotic induced diarrhoea)
453
what antibiotics can cause Clostridium difficile?
* Ciprofloxacin * Clindamycin * Cephalosporins * Co-amoxiclav (augmentin) * Carbapanems e.g. meropenem
454
how do bacteria resist antibiotics?
- target site mutation - destruction of antibiotic - prevention of antibiotic entry - remove antibiotic from bacterium
455
how do bacteria mutate target sites for antibiotics?
bacteria changes the molecular configuration of its antibiotic binding site or masks it: - flucloxacillin (or methicillin) is no longer able to bind penicillin binding protein of Staphylococci in MRSA - wall components change in enterococci and reduce vancomycin binding - vancomycin-resistant enterococci
456
how do bacteria destroy antibiotics? give examples
the antibiotic is destroyed or inactivated: - beta lactam ring of penicillins and cephalosporins can be hydrolysed by bacterial enzyme ‘beta lactamase’ meaning they are unable to bind to penicillin binding proteins and inhibit cell wall synthesis - Staphylococci produce penicillinase so penicillin but not flucloxacillin is inactivated
457
how can penicillins and cephalosporins be resisted by bacteria?
their beta lactam ring can be hydrolysed by bacterial enzyme beta lactamase, meaning they're unable to bind penicillin binding proteins and inhibit cell wall synthesis
458
how can penicillin be resisted by Staphylococci?
they produce penicillinase, so penicillin but not flucloxacillin is inactivated
459
how can bacteria prevent antibiotic entry?
bacteria modifies its bacterial membrane porin channel size, numbers or selectivity
460
how can bacteria remove antibiotics from themselves?
proteins in bacterial membranes can act as an export or efflux pump so the antibiotic is pumped out of the bacteria/microbe resulting in reduced levels and thus effect of antibiotic on bacteria/microbe: - S.aureus or S.pnuemoniae resistance to fluroquinolones - Enterobacteriacae resistance to tetracyclines
461
how are S. aureus and S. pneumoniae resistant to fluroquinolones?
proteins act as an efflux pump so the antibiotic is pumped out, thus reducing the levels and effect of the antibiotic
462
how are Enterbacteriacae resistant to tetracyclines?
proteins act as an efflux pump so the antibiotic is pumped out, thus reducing the levels and effect of the antibiotic
463
what is intrinsic natural resistance?
all subpopulation of a species will be equally resistant
464
what are examples of bacterial intrinsic natural resistance?
- aerobic bacteria are unable to reduce metronidazole to its active form thus the antibiotic is harmless to them - anaerobic bacteria lack oxidative metabolism required to take up aminoglycosides - vancomycin is not taken up by gram negative bacteria - it cannot penetrate their outer membrane since its too large
465
why are aerobic bacteria resistant to metronidazole?
unable to reduce it to its active form
466
why are anaerobic bacteria resistant to aminoglycosides?
lack oxidative metabolism to take them up
467
why are gram negative bacteria resistant to vancomycin?
cannot penetrate their outer membrane since it is too large
468
what is bacterial acquired resistance?
* a bacterium which was previously susceptible obtains the ability to resist the activity of a particular antibiotic * only certain strains or subpopulations of a species will be resistant
469
what are types of bacterial acquired resistance?
- spontaneous gene mutation | - horizontal gene transfer
470
what are examples of spontaneous gene mutations leading to acquired resistance to an antibiotic?
- new nucleotide base pair - change in amino acid sequence - change to enzyme or cell structure - reduced affinity or activity of antibiotic
471
what are types of horizontal gene transfer that lead to acquired resistance to an antibiotic?
conjugation, transduction and transformation
472
what is bacterial conjugation?
the transfer of genetic material between bacterial cells by direct cell-cell contact or by a bridge-like connection between two cells; takes place through a pilus
473
what is transformation?
- genetic alteration of a cell resulting from the direct uptake and incorporation of exogenous genetic material from its surroundings through the cell membrane - picking up naked DNA
474
what is transduction?
process by which foreign DNA is introduced into a bacterial cell by a virus or viral vector
475
what are clinically important antibiotic resistances in Gram positive bacteria?
- MRSA | - VRE
476
what is MRSA? what is it caused by?
* Methicillin resistant Staphylococcus Aureus * Staphylococcal casette cromosomi mec (SCCmec) contains resistance gene mecA * gene encodes penicillin-binding protein 2a (PBP2a) that does not bind penicillin i.e. resistance * confers resistance to all B-lactam antibiotics in addition to methicillin
477
what is SCCmec?
Staphylococcal casette cromosomi mec
478
what does SSCmec contain?
resistance gene mecA
479
what does mecA resistance gene encode?
penicillin-binding protein 2a (PBP2a) that does not bind penicillin
480
what is MRSA resistant to?
all beta-lactam antibiotics and methicillin
481
what is VRE?
* Vancomycin-resistant enterococci * plasmid mediated acquisition of gene encoding altered amino acid on peptide chain preventing vancomycin binding * promoted by cephalosporin use
482
what is VRE promoted by?
cephalosporin use
483
what are clinically important antibiotic resistances in Gram negative bacteria?
- beta-lactamases - ESBL - AmpC beta-lactamase resistance
484
what are beta lactamases?
* enzymes that hydrolyse penicillins * TEM-1 in E.coli, H. influenzae and N. gonorrhoea * SHV-1 in K. pneumoniae * but such strains typically remain sensitive to beta-lactamase inhibitors
485
what is ESBL?
extended spectrum beta lactamases
486
what do ESBLs have resistance to?
• have further mutation at active site means it can destroy more than just penicillin or amoxycillin • typically they can also inactivate: - cephalosporins e.g. cefuroxime, cefalexin, cefotaxime - combination antibiotics such as co-amoxiclav and tazocin
487
what does AmpC beta lactamases have resistance to?
• broad spectrum penicillin, cephalosporine and monobactam resistance • beta lactamase inhibitor resistant in bacteria such as Citrobacter spp. and Enterobacter spp.
488
what can AmpC beta lactamase resistance be treated with?
can be treated with quinolones or trimethoprim but may require carbapenam treatment or agents such as fosfomycin or temocillin (use for UTIs and chest infections)
489
what do we use antibiotics for?
- treatment | - prophylaxis
490
what are some specific indications for prophylaxis?
• specific indications: - endocarditis - post-splenectomy • prevention of post-surgical infection
491
what are examples of beta lactams?
- penicillins - cephalosporins - carbapenems - combinations (B lactam inhibitor/B lactam)
492
what is MRSA resistant to?
all beta lactams
493
what are beta lactams contraindicated in?
* contraindicated for people who exhibit any type of allergy to penicillins * use with caution if patient has no true IgE mediated/severe allergy
494
what is the activity of benzylpenicillin/penicillin G?
* streptococci: e.g. S.pneumo and beta-haemolytic streps (A,B,C,G) * also treats some other gram positive bacteria including clostridia (gas gangrene) * IV * narrow spectrum
495
what is the use of benzylpenicillin/penicillin G?
skin and soft tissue infection e.g. endocarditis
496
what is the resistance to benyzlpenicillin/penicillin G?
increasing resistance; enterococci are resistance
497
what is the use of phenoxymethylpenicillin/Pen V?
* bacterial pharyngitis - ‘strep throat’ * splenectomy prophylaxis * oral
498
what is the activity of amoxicillin?
* has greater activity than benzylpenicillin - broader * H. influenzae * Enterococci * Enterobactericae - E.coli, proteus, shigella
499
what are the uses of amoxicillin?
* pneumonia * skin and soft tissue infection * UTIs
500
what is the safety/resistance of amoxicillin?
- safe both orally and IV | - resistance is emerging
501
what is the activity of flucloxacillin?
- IV and oral | - S. aureus
502
what are some examples of penicillins?
- benzylpenicillin/penicillin G (IV) - phenoxymethylpenicillin/pen V (oral) - amoxicillin (IV and oral) - flucloxacillin (IV and oral)
503
what are beta lactamase inhibitors? what is their action?
* B lactamases are enzymes produced by bacteria that hydrolyse penicillins and thus make them resistant * resemble traditional B-lactam antibiotic e.g. penicillin * they bind to the B-lactamase and protect the antibiotic from degradation
504
what are examples of beta lactamase inhibitors?
- clavulanic acid - sulbactam - tazobactam
505
what is co-amoxiclav/augmentin?
combination of amoxicillin (beta lactam) and clavulanic acid (beta lactamase inhibitor)
506
what is pipercillin/tazobactam (tazocin)?
combination of pipercillin (beta lactam) and tazobactam (beta lactamase inhibitor)
507
what is an example of a bacteria treated with combination therapy?
for example E.coli exhibits B-lactamase production: - it's resistant to amoxicillin - but it's sensitive to amoxicillin and clavulanic acid
508
what are some uses of cephalosporins?
* can be used in those with non-severe penicillin allergies | * can be used to treat meningitis
509
what is resistant to cephalosporins?
C. difficile and enterococci
510
what is a 1st generation cephalosporin?
cefalexin
511
what is a 3rd generation cephalosporin?
ceftriaxone, cefotaxime (penetrates CNS)
512
what generations of cephalosporin have more activity against gram positive bacteria?
earlier generations
513
what generations of cephalosporins have more activity against gram negative bacteria?
newer generations
514
what is an example of a monobactam?
aztreonam (IV)
515
what is the activity of aztreonam (monobactam)?
only gram negative rods/bacilli
516
what are features of aztreonam (monobactam)?
- safe for those with penicillin allergies - has a lower C.diff risk - can only be used IV - has a narrow spectrum of activity
517
what are examples of carbapenems?
- meropenem - ertapenem - imipenem
518
what is the activity of carbapenems?
- extended spectrum B-lactamases | - AmpC B-lactamases
519
what are the uses of carbapenems?
hospital acquired infection (for the sickest and most at risk)
520
what do carbapenems target? what are some other features of them?
• broad spectrum, cover resistant gram negatives • expensive and have a C.diff risk • emerging resistance from carbapenemase producing enterobactericae
521
what are some examples of glycopeptides?
vancomycin and teicoplanin
522
what is the target/activity of glycopeptides?
- target the cell wall of bacteria | - gram positive only
523
what are the uses of glycopeptides?
- MRSA and other serious infections | - people with penicillin allergy
524
what must be done when using glycopeptides?
* must monitor nephrotoxicity (for vancomycin more than teicoplanin) * some resistance is possible (Vancomycin Resistant Enterococci (VRE))
525
what are examples of macrolides?
clarithromycin and erythromycin
526
what is the activity and action of macrolides?
- inhibit protein synthesis - gram positives e.g. S. aureus and atypical pneumonia pathogens as well as group A streptococci - can cover MRSA
527
what are the uses of macrolides? what is there a risk of?
- severe/atypical pneumonia - penicillin allergic patients - MRSA - risk of C. diff as well as resistance
528
what is an example of a lincosamide?
clindamycin
529
what is the activity and action of lincosamides?
- inhibit protein synthesis | - gram positives e.g. S. aureus and anaerobes and group A streptococci
530
what are uses of lincosamides? what are features/risks of it?
- cellulitis (if patient is allergic to penicillin) - necrotising fasciitis - MRSA - has a good oral bioavailability - C. diff risk
531
what are some examples of tetracyclines?
doxycycline (oral)
532
what is the activity and action of tetracyclines?
- inhibits protein synthesis | - broad spectrum
533
what are uses and risks of tetracyclines?
- cellulitis (if patient is allergic to penicillin) - MRSA - possibility of resistance
534
what is an example of aminoglycosides?
gentamicin (IV)
535
what is the activity and action of aminoglycosides?
- inhibits protein synthesis - broad spectrum - enterobacteriaceae, staphylococci, synergistically to treat streptococci
536
what is the use and risks of aminoglycosides?
- UTIs - infective endocarditis (synergistically) - can be used against extended spectrum B-lactams and AmpC B-lactams - requires monitoring due to the risk of nephrotoxicity
537
what is an example of oxazolininones?
linezolid
538
what is the activity and action of oxazolininones?
- inhibits protein synthesis | - gram positive e.g. MRSA and VRE
539
what is the use and risk of oxazolininones?
- serious/gram positive infection e.g. skin and soft tissue - good oral bioavailability and penetration - multiple side effects and interactions
540
what is an example of quinolones?
ciprofloxacin (IV and oral)
541
what is the activity of quinolones?
gram negatives more than gram positives
542
what is the use of quinolones?
- UTIs | - patients with penicillin allergy
543
what are features of quinolones?
* poor streptococcal activity * good oral bioavailability * can be used against extended spectrum B-lactams and AmpC B-lactams * C.diff risk
544
what is the action and activity of metronidazole?
- inhibits nucleic acid | - anaerobic bacteria
545
what is the use of metronidazole?
intra-abdominal infection
546
what are features of metronidazole?
* good oral bioavailability * cheap * emerging resistance
547
what is the activity and action of trimethoprim?
- folate inhibitor | - broad spectrum
548
what is the use of trimethoprim?
UTIs
549
what are features of trimethoprim?
* can be used against extended spectrum B-lactams and AmpC B-lactams * cheap * however there is increasing resistance
550
what does Pseudomonas cause?
- e.g. Pseudomonas aeruinosa - hospital acquired infection - has inherent resistance mechanisms
551
what are anti-pseudomonal antibiotics?
* pip/tazobactam * ceftazidime * aztreonam (meropenem) * gentamicin * ciprofloxacin (the only oral option)
552
23 year old woman attends with dysuria and frequency for 36 hours. diagnosed with a lower UTI. what are the likely pathogens?
- E.coli - Staph saprophticus - Proteus - Klebsiella - Enterococcus
553
23 year old woman attends with dysuria and frequency for 36 hours. diagnosed with a lower UTI. what is the treatment?
trimethoprim for 3 days (if uncomplicated and ‘well’)
554
66 year old woman, has a 3 day history of fevers and nausea. leg is hot, red and swollen. diagnosed with skin and soft tissue infection (cellulitis). what are the likely pathogens?
- S.aureus | - Beta-haemolytic streptococci: Group A, C or G streptococci
555
66 year old woman, has a 3 day history of fevers and nausea. leg is hot, red and swollen. diagnosed with skin and soft tissue infection (cellulitis). what is the treatment?
flucloxacillin +/- benzylpenicillin for 10-14 days
556
40 year old man with 2 day history of cough with sputum. diagnosed with lower respiratory tract infection (pneumonia). what are the likely pathogens?
- S.pneumonia | - ‘Atypicals’
557
40 year old man with 2 day history of cough with sputum. diagnosed with lower respiratory tract infection (pneumonia). what is the treatment?
amoxicillin/co-amoxiclav +/- darithromycin for 5 days
558
what is chicken pox?
varicella zoster virus
559
what does VZV cause? what type of virus is it?
- primary infection with this virus causes chickenpox, which may produce a mild childhood illness, although this can be severe in adults and immunocompromised patients - type of herpes virus
560
what are clinical features of chickenpox/VZV? what is the distribution/structure of the rash?
* after an incubation period of 14-21 days there is a brief period of fever, headache and malaise * rash is predominantly on the face, scalp and trunk (distribution is like a chickens feathers i.e the beak and legs are relatively untouched) * rash begins as macules and develops into papule and vesicles which heal with crusting * rash will accumulate at warmer areas e.g. shoulders and neck
561
what are complications of chickenpox/VZV?
* pneumonia - more common in adults than children * pneumonitis - healthy adults have a 15% risk * central nervous system involvement presenting as acute truncal cerebellar ataxia * exhibits viral dormancy in dorsal root or cerebral ganglion which can result in localised reactivation under immunosuppressed conditions - this is shingles (localised)
562
when are patients infectious with chickenpox/VZV? how does the virus spread? where does it replicate?
patients are infectious from 2 days before the rash appears since the virus replicates in the nasopharynx and thus can spread in the air
563
what are features of shingles? what is it?
- due to reactivation of VZV - after the primary infection, herpes zoster remains dormant in the dorsal root ganglia and/or cranial nerve ganglia and reactivation results in shingles - a person with shingles (particularly if the rash is weeping) could cause chickenpox in a non-immune person after close contact and touch
564
what are clinical features of shingles? what are the most common sites and what is the rash like?
* pain (neuropathic) and tingling in a dermatomal distribution precede the rash by a few days * the rash consists of papules and vesicles in the same dermatome * the most common sites are the lower thoracic dermatomes and the opthalmic division of the trigeminal nerve (most common)
565
what are red flag signs of shigella? what can it be a hallmark of?
- shingles can be a hallmark of HIV - red flag if multiple dermatomes are involved or peripheral dermatomes involved - these are unusual signs and need proper investigation for immunocomprimisation i.e. HIV
566
what are features of foetal varicella syndrome?
- bilateral limb hypoplasia and scarring - seen in 10-15% chickenpox in pregnancy - if maternal chickenpox in first half of pregnancy then 2% risk of foetal varicella syndrome in infants
567
what is commonly mistaken for chicken pox?
hand foot mouth enterovirus
568
how can chickenpox be differentiated between hand foot mouth enterovirus?
pop lesion and absorb the fluid and then test for chickenpox or enterovirus to find out what it is
569
what does syphilis cause?
classic infection that causes lesions on the palms, toes and back
570
what is eczema herpetica?
- rare but severe disseminated infection that generally occurs at sites of skin damage produced by atopic dermatitis, burns, long term use of topical steroids or eczema - dermatological emergency
571
what are pathogens?
microorganisms capable of causing disease
572
what is infectivity?
the ability of a pathogen to become established in host, can involve adherence and immune escape
573
what is virulence?
the ability of a pathogen to cause disease once established
574
what is invasiveness?
the ability of a pathogen to penetrate mucosal surfaces to reach normally sterile sites
575
what are virulence factors?
microbial factors that cause disease
576
what are viruses?
- need rapid cell entry - free virus in blood stream is easily neutralised - infected cells are destroyed
577
what is the humoral response to viruses? how does each component affect a virus?
* IgA - Blocks binding * IgM - agglutinates particles and makes it difficult to enter cells * complement - opsonisation and cell lysis * antibodies - neutralise toxins
578
what is a cell mediated response to a virus?
* interferon (from T helper or T killer cells) has antiviral action - it induces anti-viral protein DAI (Double stranded RNA activated inhibitor of translation) on nearby cells so they cannot get infected * cytotoxic T lymphocytes kill infected cells (so any virus in cell cannot replicate)
579
what is DAI?
double stranded RNA activated inhibitor of translation | - anti-viral protein induced by interferon
580
what does interferon do against viruses?
induces DAI on nearby cells so they cannot get infected
581
what do cytotoxic T lymphocytes do against viruses?
cytotoxic T lymphocytes kill infected cells (so any virus in cell cannot replicate)
582
what is the process of cell mediated response to viruses?
* 3-4 days post infection the cytotoxic T lymphocyte activity increases * peaks at 7-10 days then declines * cytotoxic T lymphocytes eliminate virus infected cells and so eliminate sources of new viral products
583
what are examples of virueses causing direct cell cytotoxicity?
* influenza virus to respiratory epithelium * varicella zoster virus (chicken pox) to skin cells * yellow fever virus to liver cells * HIV to CD4 T-cells
584
what cell does influenza target with direct cell cytotoxicity?
respiratory epithelium
585
what cell does VZV target with direct cell cytotoxicity?
skin cells
586
what cell does yellow fever virus target with direct cell cytotoxicity?
liver cells
587
where does the damage caused to cells in viral infection come from?
much of the damage to cells in viral infection is indirect and caused by the innate or adaptive immune response
588
how do bacteria enter the host?
* respiratory tract * gastrointestinal tract * skin/mucous membrane break e.g wound
589
what determines the defence mechanism employed against bacteria?
number of organisms, virulence and location
590
what defence mechanism does low number or virulence cause?
phagocytes activate
591
what defence mechanism does high number or virulence cause?
immune response
592
what defence mechanism does extracellular bacteria cause?
antibody response
593
what defence mechanism does intracellular bacteria cause?
cellular response
594
what are attributes of a bacterial pathogen?
- bacteria compete with host cells and colonising flora - adhesins - biofilms
595
how do bacteria compete with host cells and colonising flora?
- sequestering nutrients - using novel metabolic pathways - out-competing other micro-organisms
596
what do adhesins in bacteria do?
help bacteria bind to mucosal surfaces
597
what are types of bacterial adhesins do?
• fimbriae and pili filamentous proteins e.g Neisseria gonorrhoea • lipid e.g. lipid teichoic acid of Streptococcus pyogenes • glycosaminoglycans of Chlamydia sp.
598
what do bacterial biofilms do? where are they seen?
- bacteria can stick together on a surface by secreting an extracellular polymeric substance of proteins, polysaccharides and DNA - helps protect against antimicrobials - seen in dental plaque, prosthetic materials and in ottis media (middle ear infection)
599
what are examples of bacteria with biofilms?
* S.aureus * Streptococcus mutans * Pseudomonas aeruginosa
600
how do Neisseria evade host defences?
secrete proteases which lyse IgA
601
how does B. pertussis evade host defences?
secretes adhesion molecules
602
how does S. pneumoniae evade host defences?
has a polysaccharide capsule that prevents phagocytosis
603
how does S. pyogenes evade host defences?
releases M protein that inhibits phagocytosis
604
how do Staphylococci evade host defences?
produce coagulase that forms a fibrin coat round the organism thereby protecting it
605
how does Pseudomonas evade host defences?
secretes elastase which inhibits C3a and C5a (attracts neutrophils to site of inflammation)
606
how does Mycobacterium evade host defences?
escapes from phagolysosome and lives in cytoplasm
607
what does immune response and its effectiveness depend on in protozoal infection?
location of parasite in host
608
what does protozoa in the blood trigger?
humoral immunity
609
what does protozoa in the tissue trigger?
cell mediated immunity
610
what are features of helminths?
* do not multiple in humans (eggs formed) * not intracellular * few parasites carried * poor immune response
611
what is the life cycle of schistosomiasis?
snail > larvae > human > liver > intestinal mesentery (bladder veins) > male + female (adult worms) > eggs > faeces/urine > snails
612
what is the immune response to worms/helminths?
* IgG and IgE produced * IL5 - eosinophil production * IL3 - mast cell growth * eosinophil basic protein is toxic to worms
613
how do worms evade host defences?
* decreased antigen expression by adult worms * glycolipid/glycoprotein coat is host derived so not perceived as foreign to the immune system - utilises host self antigens
614
what cells is there an upregulation of adhesion molecules on in inflammation?
* monocytes * neutrophils * endothelial cells (IL-1, TNFa)
615
what mediates chemotaxis in inflammation?
* IL-8 | * C5a
616
what mediates degranulation in inflammation?
* IL-8 * C5a * IFN gamma * LPS
617
what mediates vascular permeability in inflammation?
* Prostaglandins | * Leukotrienes
618
what mediates vasodilation in inflammation?
* Prostaglandins * Leukotrienes * Kinins
619
what are examples of passive immunisation?
* transplacental transfer * colostrum (in breast milk) * inject preformed antibody * tetanus toxoid * snake venom
620
what does active immunisation elicit? how does it achieve this?
* protective immunity * immunological memory * achieved by: natural infection and vaccine administration
621
what are some types of vaccines?
* inactivated (killed) * attenuated (avirulent) * bacteria or viruses * toxoid vaccines (inactivated toxins)
622
what are notifiable diseases?
- diseases, infections and conditions specifically listed as notifiable under the Public Health (Infectious Diseases) Regulations 1988 - it is the legal obligation for any doctor that suspects a case to inform the Proper Office of the Local Authority
623
what diseases are not notifiable?
HIV, bird flu or variant Creutzfeldt-Jakob (vCJD) disease (mad cow disease)
624
what are some notifiable diseases from A to F?
- acute encephalitis - acute infectious hepatitis - acute meningitis - acute poliomyelitis - anthrax - botulinism - brucellosis - cholera - diphtheria - enteric fever - food poisoning
625
what are some notifiable diseases from H to R?
- haemolytic uraemic syndrome - infectious bloody diarrhoea - invasive group A streptococcal disease - Legionnaires disease - leprosy - malaria - measles - meningococcal septicaemia - mumps - plague - rabies - rubella
626
what are some notifiable diseases from S to Y?
- SARS - scarlet fever - smallpox - tetanus - TB - typhus - viral haemorrhagic fever - whooping cough - yellow fever
627
what are notifiable diseases that are 'scary'?
* anthrax * rabies (no treatment) * cholera * leprosy * malaria
628
what are notifiable diseases that are vaccine preventable?
* acute poliomyelitis (polio) * measles * mumps * rubella
629
what are notifiable diseases that need specific control measures?
* acute infectious hepatitis * scarlet fever * tuberculosis
630
what is the role of disease surveillance?
- detection of any changes in a disease | - allows the development of interventions targeted at vulnerable groups
631
what is involved in detection of any changes in a disease?
- outbreak detection - early warning - forecasting - extent and severity of disease - risk factors
632
how is the community protected from notifiable diseases?
- investigate to see who might have been exposed to the disease - identify and protect vulnerable persons - exclude high risk persons from high risk setting - educate, inform and raise awareness
633
how can you investigate to see who might have been exposed to a notifiable disease?
* contact tracing | * partner notification
634
how can you identify and protect vulnerable persons from notifiable diseases?
* chemoprophylaxis * immunisation * isolation
635
what are the types of immunoglobulin?
G, A, M, E and D
636
what are the two forms of immunity?
active and passive
637
what are types of active immunity?
* cell-mediated immunity | * antibody-mediated immunity
638
what does vaccination stimulate in active immunity?
vaccination stimulates immune response and memory to a specific antigen/infection
639
what are vaccines made from? give examples for each
- inactivated (killed) e.g. pertussis and inactivated polio - attenuated live organism e.g. yellow fever, MMR, polio and BCG - secreted products e.g. tetanus & diptheria toxins - the constituents of cell walls/subunits e.g. Hep B - recombinant components - experimental
640
what are features of polysaccharide vaccines?
- polysaccharide antigens are not as immunogenic as protein antigens (protein vaccine results in a stronger response) - protection is not long-lasting - response in infants and young children often poor
641
what are features of live attenuated vaccines? when shouldn't they be given?
- must replicate in the vaccinated individual to produce an immune response - takes time (days or weeks) to replicate - usually does not cause disease but some may cause a mild form of the disease - avoid giving live attenuated vaccines to those who are immunocompromised since they are at risk of infection
642
what is passive immunity?
protection provided from the transfer of antibodies from immune individuals
643
what are examples of passive immunity?
• most commonly it is cross-placental transfer of antibodies from mother to child e.g. measles, pertussis • or, via transfusion of blood or blood products including immunoglobulin e.g. Hep B • passive immunity provided by injection of human immunoglobulin containing antibodies to the target infection
644
what does passive immunity result in?
* protection is temporary - usually only a few weeks or months * temporarily increases person’s antibody level to that specific infection * protection gained within a few days but lasts only a few weeks
645
where is human normal immunoglobulin derived from?
human normal immunoglobulin (HNIG) derived from the pooled | plasma of donors and contains antibodies to infectious agents that are currently prevalent in the general population
646
what are human normal immunoglobulins used for?
used to protect immunocompromised children exposed to measles and of individuals after exposure to hepatitis A
647
what is primary vaccine failure?
person doesn't develop immunity from vaccine
648
what is secondary vaccine failure?
initially responds but the protection wades over time
649
what can meningococcal infection present as?
meningitis or septicaemia
650
what is meningococcal infection caused by? what is it seen as under a microscope?
- caused by Neisseria meningitis (gram negative); 10-20% carry this in the back of the throat - seen as gram negative purple diplococci under microscope
651
how is meningococcal infection spread?
- infection is not easily spread - transmitted person to person by inhaling respiratory secretions from the mouth and throat or by direct contact (kissing) - close prolonged contact usually required - bacteria do not live long outside the body
652
what is the epidemiology of meningococcal infection?
* majority of infections occur in children (less than 5) * peak incidence in under 1s * smaller secondary peak in young adults (age 15-19) * less than 5% of cases occur in clusters * most cases are sporadic * outbreaks common among teenagers and young adults e.g. in schools and universities * marked seasonal variation with peak in winter * the winter season coincides with that of influenza
653
what are the serogroups of meningococcal infection?
distinct serogroups, according to their polysaccharide outer capsule
654
what are the common pathogenic serogroups? what do they cause?
* the most common pathogenic serogroups are groups B, C, A, Y and W135 * most disease in the UK is caused by serogroups B (59%) and C (36%) * significantly fewer cases caused by serogroup C since routine vaccination introduced
655
what are complications of meningococcal infections?
* brain abscess * brain damage * seizure disorders * hearing impairment * focal neurological disorders * organ failure * gangrene * auto-amputation due to arterial occlusions * death
656
what antibiotics are given for meningococcal infections?
- Cefotaxime | - Ceftriaxone
657
what are the outcomes of meningococcal infections?
* case fatality rate around 10% | * more deaths caused by septicaemia than meningitis
658
what is done to prevent meningococcal infections?
- notification - contact tracing - prophylaxis
659
what is contact for meningitis? what does close contact include?
- contact for meningitis is taken to be any person having close contact with a case in the past 7 days - close contact includes: • kissing • sleeping with • spending the night together • spending in excess of eight hours in the same room
660
what advice is given to meningococcal contacts?
- warn about symptoms and signs - glass test: petechial spots do not blanch on pressure - contact telephone number
661
how is antibiotic chemoprophylaxis used to treat meningococcal infection?
- for close, usually household contacts - Ciprofloxacin (older children and adults) or Rifampicin (not for pregnant women) - for nasal carriage - reduces spread - does not stop the disease if already incubating it
662
how is immunisation used to treat meningococcal infection?
- if the serotype of meningococcus is vaccine preventable, a vaccination may be offered to unprotected contacts - depends on serogroup - but remember neither vaccine efficacy nor coverage is ever 100% - routine childhood immunisations: men B and C
663
what is a mneumonic for gram positive bacteria?
sexy students can look bad comemorning - Streptococcus spp. - Staphylococcus spp. - Corynebacterium spp. - Listeria spp. - Bacillus spp. - Clostridium spp.
664
what is a mneumonic for gram negative bacteria?
huge vaginas can never provide pleasure - Helicobacter - Vibrio cholera - Coliforms - Neisseria - Parvobacteria - Pseudomonas
665
what is a mneumonic for DNA viruses?
HAPPH - Herpes viridae - Adenovirus - Parvovridae - Papopviridae - Hepaviridae
666
what are anaerobic gram positive bacilli?
Clostridium
667
what are some species of Clostridium?
- C. perfringens - C. tetani - C. botulinium - C. difficile
668
what are aerobic gram positive bacilli?
- Cornyebacterium - Listeria - Bacillus
669
what are some species of Cornyebacterium?
C. diptheriae
670
what are some species of Listeria?
L. monocytogenes
671
what are some species of Bacillus?
B. anthracis | B. cereus
672
what are some gram negative cocci?
Neisseria | Moraxella
673
what are some species of Moraxella?
M. catarrhalis
674
what are some species of Bacteroides?
B. fragilis
675
what are some aerobic gram negative bacilli with fastidious growth requirements?
- Parvobacteria | - Helicobacter
676
what are some species of Parvobacteria?
- Haemophilus influenzae - Bordatella pertussus - Leigonella pneumonphilia - Brucella - Campylobacter jejuni
677
what are some are some gram negative aerobic bacilli that are lactose fermenters?
- Eschericia (E. coli) | - Klebsiella (K. pneumoniae)
678
what are some gram negative aerobic bacilli that are non-lactose fermenters?
- Salmonella - Shigella - Proteus
679
what are some species of Salmonella?
- S. typhi - S. paratyphi - S. enterica
680
what are some species of Shigella?
- S. sonnei | - S. dysenteriae
681
what are some species of Proteus?
- P mirabilis
682
what are some antibiotics which inhibit cell wall synthesis?
- glycopeptides | - beta lactams
683
what are some examples of glycopeptides?
Vancomycin and Teicoplanin
684
what are Vancomycin and Teicoplanin used for (glycopeptides)?
- severe staph infections e.g. MRSA/C. difficile | - must be monitored to prevent ototoxicity and nephrotoxicity
685
what are some examples of beta lactams?
- penicillins - cephalosporins - carbapenems
686
what are some types of penicillins?
- benzylpenicillin - flucoxacillin - ampicillin/amoxicillin
687
what is benzylpenicllin used for?
Strep. infections, pneumococcal pneumonia, meningococcal meningitis, gonococcal infection, syphillis
688
what is flucloxacillin used for?
S. aureus, S. pyogenes
689
what is ampicillin/amoxicillin used for?
UTIs, RTIs, listeria, meningitis, entercocci infections, S. pneumonia causing bronchitis
690
what are cephalosporins used for?
S. aureus, streptococci, nisseriae, Haemophilus, coliforms
691
what are examples of carbapenems?
imipenem, ertapenem
692
what are carbapenems used for?
enterobacteriae, anaerobic bacteria
693
what are cautions and side effects of glycopeptides?
cautions: renal impairment, history of deafness, pregnancy SEs: nephrotoxicity, ototoxicity, blood disorders
694
what are contraindications and side effects of benzylpenicillin and flucloxacillin?
CIs: penicllin hypersensitivity SEs: hypersensitivity reactions
695
what are contraindications and side effects of ampicillin/amoxicillin?
CIs: penicillin hypersensitivity SEs: nausea, vomiting
696
what are contraindications and side effects of cephalosporins?
CIs: cephalosporin sensitivity (10% allergic to penicillin will also be ceph sensitive) SEs: antibiotic associated colitis, Stephens-Johnson syndrome
697
what are contraindications and side effects of carbapenems?
CIs: breast feeding SEs: increased platelet count (ertapenem), neurotoxicity at very high doses
698
what are categories of antibiotics that inhibit nucleic acid synthesis?
- inhibit folate synthesis - inhibit DNA gyrase - binds to RNA polymerase - DNA strand breaks
699
what are examples of antibiotics that inhibit folate synthesis?
- trimethoprim - sulfonamides: sulfamethoxazole - co-trimoxazole: trimethoprim and sulfamethoxazole
700
what is trimethoprim used for?
UTI (not in pregnancy), prostatitis, acute/chronic bronchitis
701
what is co-trimoxazole used for?
PCP treatment and prophylaxis
702
what are examples of antibiotics that inhibit DNA gyrase?
fluoroquinolones: ciprofloxacin, ofloxacin, levofloxacin
703
what are uses of fluroquinolones?
Strep. viridans, Strep. pyogenes, Pseudomonas, H. influenza, campylobacter, Chlamydia spp.
704
what are examples of antibiotics that bind to RNA polymerase?
rifampicin
705
what are uses of rifampicin?
Staph and Strep., mycobacteria (quad. TB treatment)
706
what are examples of antibiotics that cause DNA strand breaks?
nitroidimazoles: metronidazole
707
what are uses of nitroidimazoles?
anaerobes, parasites e.g. Giardia lambia, prophylaxis in GI surgery
708
what are contraindications and side effects of trimethoprim?
CIs: blood dyscrasias cautions: pregnancy SEs: hyperkalaemia, depression of haematopoiesis
709
what are contraindications and side effects of co-trimoxazole?
CIs: porphyria SEs: hyperkalaemia, rash
710
what are contraindications and side effects of fluroqinolones?
caution: epilepsy, G6PD deficiency, myasthenia gravis SEs: dyspepsia, sleep disorders, rash pruritus NB: predispose to MRSA as excreted through the skin and kills commensal organisms
711
what are contraindications and side effects of rifampicin?
CIs: jaundice SEs: orange discolouration of saliva and urine, anorexia, nausea and vomiting, haemolytic anaemia
712
what are contraindications and side effects of nitroidimazoles?
CIs: interaction with alcohol -> profuse vomiting SEs: taste disturbance, anorexia
713
what are examples of antibiotics that inhibit protein synthesis?
- chloramphenicol - macrolides - tetracyclines - aminoglycosides
714
what are uses of chloramphenicol?
- H. influenzae meningitis, epiglottitis, Chlamydia, richkettsiae - used widely in the developing world - extended periods of treatment can cause bone marrow depression - neonatal toxicity -> grey baby syndrome
715
what are examples of macrolides?
Clarithromycin and Erythromycin
716
what are uses of macrolides?
Strep. pneumoniae, S. aureus, Legionella, Chlamydia, mycoplasma pneumoniae
717
what are examples of tetracyclines?
Tetracyclin and Doxycycline
718
what are uses of tetracyclines?
- broad spectrum | - Strep. pneumonia, Strep. viridans, Strep. pyogenes, S. aureus, Chlamydia, mycoplasma
719
what are examples of aminoglycosides?
Gentamycin and Streptomycin
720
what are uses of gentamycin?
S. aureus, gram negative bacilli, used for severe sepsis
721
what are uses of streptomycin?
TB
722
what are contraindications and side effects of chloramphenicol?
CIs: pregnancy, breast feeding SEs: blood disorders, optic neuritis, erythema multiforme, grey syndrome (abdominal distension, cyanosis, circulatory collapse)
723
what are contraindications and side effects of macrolides?
CIs: hepatic impairment (azithromycin) caution: neonates <2 weeks risk of hypertrophic pyloric stenosis SEs: rash, arrhythmias, Stephens-Johnson syndrome
724
what are contraindications and side effects of tetracyclines?
CIs: children <12 due to deposition in bone and teeth leading to hyperplasia. renal disease SEs: dysphagia, oesophageal irritation, photosensitivity, headache, visual disturbance
725
what are contraindications and side effects of aminoglycosides?
CIs: myasthenia gravis SEs: nephrotoxicity, auditory and vestibular damage. prolonged therapy -> hypomagnesaemia