Microbiology Flashcards
(216 cards)
1
Q
What is a commensal?
What is an opportunist pathogen? What is virulence/ pathogenicity? What is asymptomatic carriage?
A
An organism which colonises the host but causes no disease in normal circumstances.
Microbe that only causes disease if host defences are compromised.
The degree to which a given organism is pathogenic.
When a pathogen is carried harmlessly at a tissue site where it causes no disease.
2
Q
How are bacteria named? Most of what surfaces are colonised by bacteria? Gram positive bacteria turn what colour? Gram negative bacteria turn what colour?
A
Staphylococcus= genus, aureus= species.
Mucosal surfaces
Purple
Pink with subsequent stain
3
Q
What bacteria requires a special stain? Gram positive bacteria have what? This connected to what?
A
TB bacteria
Ziehl-Neelsen stain
Single phospholipid bilayer
Peptidoglycan- forms dense polymer around cell
4
Q
What does gram negative bacteria have? Some form what when conditions are not good?
A
Two membranes- thin layer peptidoglycan, outer membrane and lipopolysaccharide (endotoxin)= body’s toxic shock reaction
Spores- resistant to harsh chemicals, stores DNA until conditions better again e.g. cause of anthrax
5
Q
Why do gram-negative bacteria appear pink with gram stain? Why do gram positive bacteria appear purple?
A
Cells lose outer lipopolysaccharide membrane and crystal violet-iodide complexes, pink with counterstain.
Decoloriser dehydrates the cell wall and CV-I gets trapped in multi-layered peptidoglycan, purple with counterstain.
6
Q
E.g. of gram positive+ cocci? Gram negative+ cocci?
A
Staphylococci, streptococci, entercocci, anaerobic= peptostreptococci
Neisseria, mortadella, anaerobic= villanella spp
7
Q
E.g. of gram positive+ bacilli? Of gram negative + bacilli?
A
Bacillus e.g. B.anthrancis clostridia, corynebacteria e.g. C.diptheriae
E.coli, campylobacter, pseudomonas, salmonella, shigella, proteus
8
Q
E.g. of staphylococcus? E.g. of Beta haemolytic strepto? Alpha-haemolytic strepto? Non-haemolytic?
A
S.aureus, s.epidermis
S.pyogenes, s.agalactiae
S.pneumoniae, s.oralis, s.milleri, s.sanguis
S.bovis
9
Q
E.g. of anaerobic gram positive? Enterococcus? What gram + bacteria are chains? Clusters? Tests for both of these?
A
Peptostreptococcus
E.faecalis
Chains= strepto, clusters= staphylococcus, strep test= haemolysis on BA, coagulase or DNAase test
10
Q
Types of haemolysis tests and results? Test for staphylococcus?
A
Beta= beta haemolytic strep- antigenic group A,B,C,G, alpha- optochin test, sensitive= s.pneumoniae, resistant= viridans strep.
Coagulase, += s.aureus, -= coagulase negative staphylococcus
11
Q
Class of anaerobic gram negative rods? 2 classes of aerobic gram negative rods? Tests for gram negative bacilli?
A
Bacteroides, coliforms and vibrio
Appearance on MacConkey or CLED or XLD
Non lactose fermentation= e.g. shigella, salmonella, pseudomonas, proteus–> oxidase test
Lactose fermentation= enterobacteriaceae (coliforms) e.g. ecoli, Klebsiella–> biochemical identification e.g. API strip and sensitivity tests
12
Q
E.g. of bacteria with capsule? Cell wall made up of what? What do gram positive have and not have? Gram negative?
A
Pneumonia
PPL membrane
Single cytoplasmic membrane, large amount of peptidoglycan on outer surface, not endotoxin (lipopolysaccharide)
Two membranes, smaller amount of peptidoglycan, endotoxin–> endotoxic shock
13
Q
Mucosal surfaces are areas open to bacterial colonisation? 4 things needed to be kept sterile? Some can store themselves in what? Bacterial conditions?
A
Nasal cavity, larynx, stomach, colon
Lungs, gall bladder, kidneys, eyes
Spores- which are very hardy and need to be autoclaved in order for them to be destroyed, only certain types
Between -80 and +80 degrees, pH= between 4-9, 2 hours- 3 months= water/ desiccation
14
Q
How would you measure bacterial growth? Divide by what? Growth lag is due to what? Then there is what growth?
A
By shining light on bacteria and measuring absorption
Bacteria are taking in nutrients needed to divide and grow, then exponential growth until nutrient runs out, viable= death phase
15
Q
Endotoxin produced by what? Exotoxin?
A
Mostly gram negative, action= non-specific, stable on exposure to heat, cannot be converted to a toxoid
Gram +ve and -ve= proteins, action is specific: can inhibit NS–> botulism, stimulate–> tetanus
Unstable on exposure to heat , mostly gram +ve, can be converted to a toxoid
16
Q
2 stages of bacterial genetics? 3 forms of genetic variation? Plasmids initially known as what?
A
Transcription- RNA polymerase on bacterial chromosome–>mRNA, translation- occurs at 30S/ 50S ribosome to produce proteins
Base substitution, deletion, insertion
R (resistance) factor
17
Q
3 ways of gene transfer?
A
Transformation- genetic alteration of a bacterial cell via uptake of exogenous substance e.g. via plasmid
Transduction- process by which foreign DNA is introduced into a bacteria via a vector or virus e.g. a bacteriophage (virus)
Conjugation- transfer of genetic material between bacterial cells by direct cell-cell contact e.g. via sex plus
18
Q
3 features of staphylococcus? Reason for coagulase clumping/ no clumping? Common clinical presentation of staph aureus?
A
Normal habitat= nose and skin, at least 40 species and can be coagulase positive/ negative
Coagulase converts fibrinogen–> fibrin i.e. clot- some produce it to protect against WBCs e.g. staph. aureus
Pain in shoulder, elevated temp, MRI scan- disc injection and osteomyelitis C6 and C7
19
Q
Treat staph. aureus? Coagulase positive or negative? Spread by what? MRSA resistant to what? Virulence factors?
A
Flucloxacillin for 3 months, responsible for 90% osteomyelitis
Coagulase positive, spread by aerosol and touch
B-lactams, gentamicin, erythromycin, tetracycline
Pore-forming toxins- e.g. PVL which causes haemorrhage pneumonia
Alpha-haemolysin- induce apoptosis at low levels or widespread necrosis at high levels
Proteases–> scalded ski syndrome
Toxic shock syndrome toxin- stimulates cytokine release
Protein A- surface protein binds immunoglobulins in wrong orientation
20
Q
E.g. of coagulase negative staphylococci? Main virulence factor?
A
Staphylococcus epidermis- opportunistic infections in prosthetic limbs and catheters, persistent biofilms
Staph saprophyticus- acute cystitis
21
Q
Streptococci can be classified in what 3 ways? What 3 colours with haemolysis?
A
Haemolysis, Lancefield typing, biochemical properties
Alpha= green- brown, Beta= clear/ colourless, gamma= no lysis
22
Q
What is Lancefield typing? 2 most important groups?
A
Method of grouping coagulase negative bacteria based on bacterial carb cell surface antigens
20 groups= A-H and K-V
A- strep. pyogenes, and B- strep agalactiae; neonatal infections
23
Q
Infections caused by strepto pyogenes? Complications? Assessment of risk estimated with what? Virulence factors?
A
Wound infections e.g. cellulitis, tonsillitis and pharyngitis, otitis media, Scarlet fever (by erythrogenic toxin)
Rheumatic fever, glomerulonephritis, needs prompt treatment
Anti-streptolysin O titre
Enzymes or toxins
24
Q
Common presentation of strepto pneumo? Infections? Pre-disposing factors? Virulence factors?
A
Heavy smoker with nasal congestion and fever, 2 days later= cough, severe chest pain, rust-coloured sputum, CXR= fluid filled
Pneumonia, otitis media, sinusitis, meningitis
Impaired mucus trapping, hypogammaglobulinaemia, asplenia- no tuftsin–> impaired phagocytosis, diabetes, renal disease, sickle cell disease, young age
Polysaccharide capsule, teichoic acid- binds to choline receptors, peptidoglycan- protects bacteria, pneumolysin cytotoxin
25
Viridans strep also known as? Some cause what? Important in what? Most pathogenic are what group? Causes what?
Oral strepto, alpha or non-haemolytic
Dental caries and abscesses
Infective endocarditis: s.sanguinis, s.oralis
Milleri group- s.intermedius, s.anginosis, s.constellatus
Deep organ abscesses e.g. in brain and liver
26
Common presentation of corynebacterium diphtheria? Treatment? Spread by? Toxin does what? Toxin recognition using what? Prevention?
Child with severe sore throat, fever and malarse for 2 days, lymphadenopathy in neck, rapid breathing, thick greyish membrane on tonsils
Anti-toxin and erythromycin
Droplet spread
Inhibits protein synthesis, Elek plate, toxoid vaccination
27
3 parts of lipopolysaccharide endotoxin? Bacteria has not H antigen since no flagellum? Does have H antigen since does have flagellum?
Lipid A- toxin portion anchored in outer leaflet of outer membrane
Core R antigen- short chain of sugars, some unique to LPS
Somatic O antigen- highly antigenic repeating chain of oligosaccharides
Shigella
Salmonella- does have flagellum
28
Features of enterobacteria (coliforms)?
Rods/ bacilli, most are motile, some are intestinal parasites, able to grow in anaerobic conditions, MacConkey used to differentiate lactose and non-lactose fermenting
29
Most facultative anaerobe in gut? Has what? Infections caused? There are many what? They share a common what?
```
E.coli
Flagella
Wound infections, UTIs, gastroenteritis, travellers' diarrhoea, bacteraemia, meningitis in infants
Serotypes (pathovars)
Common core genome
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30
Pathogenic e.coli contains what not in commensal e.coli? Many have acquired pathogenicity how? How is travellers diarrhoea caused?
Blocks of genes
By mating and acquiring pathogenic blocks of genes
By ETEC strain, pilli= adhere to tissue of SI, labile toxin released--> alters role of Gs protein on GI cell surface--> adenyl cyclase not stimulated--> more Cl- released into GI lumen
31
4 species of shigella? Symptoms? Enter gut via what? Cross epithelial cell layer where what happens? Eventually destroyed by what? Some release what which doe what? Also from some what?
S.dysenteriae, s.felxneri, s.boydii, s.sonnei (commonest)
Low infective dose
Severe blood diarrhoea, frequent passage of stools, small volume pus and blood, prostrating cramps
M cells, engulfed by macrophages--> apoptosis and released of damaging free radicals, inflammatory response and cell damage
Neutrophils
Shiga toxin- disrupts protein synthesis--> necrosis
E.coli e.g. EHEC
32
2 species of salmonella? Infections x3?
S.enterica--> salmonellosis and s.bongori- reptile contact
Gastroenteritis- milk and poultry, 6-36 hour incubation, resolves in week, localised infection
Enteric fever- typhoid, systemic disease, by type and paratyphi, faecal-oral spread, fever, headache, dry cough
Bacteraemia- bacteria in the blood- uncommon
33
Pathogenesis of salmonella?
Ingestion of contaminated food/ water, high infective dose
| Mediates endocytosis across gut lumen
34
Salmonella causing gastroenteritis?
Bacteria presence results in chemokine release and neutrophil recruitment, neutrophil-induced tissue injury
Fluid and electrolyte loss due to cell damage resulting in diarrhoea
Inflammation/ necrosis of gut mucosa
35
Salmonella causing enteric fever?
To basolateral membrane of cells in intestinal lumen- inflammation and ulceration
Initially= little damage to gut mucosa
Bacteria engulfed and survives, then spreads to lymph nodes
Enters bloodstream via thoracic duct, then multiples in macrophages of liver, spleen and bone marrow--> septicaemia, massive fever
Spreads to gall bladder from liver where person can be in carrier state from 1 year to rest of life
36
What does Klebsiella pneumoniae cause?
Opportunistic, nosocomial infections, pneumonia, bloodstream infections, wound/ surgical infections, meningitis
37
Features of vibrio cholera? There is no what and why? Treatment? Virulence determinants?
Facultative, curved rods/ bacilli with single polar flagellum
Faecal-oral route, high infective dose- sensitive to acid, incubation= 5 hours, results in rice-water stools
60% mortality- can lose 20 litre/ day plus electrolytes
Blood or fever- no invasion/ damage of mucosa
80% with oral rehydration
Pilli- for colonisation, cholera toxin- uncontrolled cyclic AMP production, protein kinases, loss of Cl- and Na+--> H2O loss
38
Features of pseudomonas aeruginosa?
Motile- single polar flagellum, opportunistic, multiple antibiotic resistance
Acute infections: localised- burn surgical wounds, UTIs, keratitis, systemic- neutropenic, ICU patients- nosocomial pneumonia
Chronic infection: cystic fibrosis suffers- dehydrated lung mucus--> bacteria grow
39
Features of haemophilia influenzae? Causes what? Only grow on what?
Exclusively human parasite, nasopharyngeal carriage in 25-80% population, infections mainly young children and adult smokers, non-motile
Meningitis crosses BBB, epiglottitis, sinusitis, otitis media, bacteraemia, cystic fibrosis and COPD lung infections
Chocolate agar- blood agar heated to 80 degrees to allow release of haem by RBCs
40
Virulence determinants of haemophilus influenzae?
Pilli- adherence to epithelial cells and mucin, commensals and resp tract pathogens= non capsulate, invasive strains (penetrate nasopharyngeal epithelium)= capsulate
Lipopolysaccharide endotoxin--> inflammation
41
Features of bordetella pertussis (Beta- Proteobacteria)?
Pertussis= whooping cough, short rods, highly contagious with low infect dose, aerosol transmission
Adhere to ciliated epithelia of upper resp tract
42
Symptoms of bordetella pertussis and can lead to what?
Non-specific flu-like symptoms followed by paroxysmal coughing (cough--> inhalation resulting in whooping sound)
Sub-conjunctival haemorrhage
43
2 species of neisseria? Where found during infection? Prevalence, transmission and symptoms of n.meningitis?
Non-flagellated diplococci
N.meningitis, n.gonorrhoeae
Polymorphonuclear lymphocytes of CSF or urethral discharge
In nasopharynx of 5-10% population, aerosol transmission, crosses NP epithelium and enters bloodstream in small proportion of colonised individuals
Asymptomatic if low/ septicaemia if high
44
Virulence determinants of n.meningitis?
Capsulated in nasopharynx, capsule= anti-phagocytic
Pilli= cell invasion
Lipopolysaccharide= cytokine cascade--> sepsis
45
Transmission and symptoms of n.gonorrhoea?
Not a commensal but can be asymptomatic (30% of infected females), person to person only
STD--> urethritis with additional infection of female genitalia, can lead to infection of Fallopian tubes if infection ascends
Non-capsulated unlike n.meningitis
46
E.g. of e-Proteobacteria? Features and symptoms of campylobacter? Virulence factors?
Campylobacter- C.jejuni, C.coli
Spiral rods/ bacilli, most common cause of food poisoning in UK and US, undercooked poultry, low infective dose, mild-severe diarrhoea often with blood, shed in faeces for around 3 weeks
Invasins- invades ideal and colonic epithelial cells--> local acute inflammatory response i.e. tissue damage
Cytolethal distending toxin (CDT)- arrests cell cycle meaning target cells swell and lyse
47
Features of helicobacter pylori? Virulence factor?
Requires CO2, spiral shaped, present in 50% of global population but only fraction will develop disease
Major role in gastritis and peptic ulcer disease
Implicated in gastric adenocarcinoma
Urease- hydrolyses urea to generate ammonia to act as a buffer to gastric acid
48
Features of chlamydia and 2 developmental stages in growth cycle?
```
Very small, non-motile
Elementary bodies (EBs)- dormant: infectious, enter cell through endocytosis, prevents phagosome fusion
Reticulate bodies (RBs)- metabolically active and fragile
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49
Features and symptoms of chlamydia trachoma's?
Most common STD
Can spread to uterus and ovaries--> pelvic inflammatory disease, usually asymptomatic, can cause conjunctivitis, trachoma- blindness spread via flies
50
Most common sites/ modes of infection caused by gram negative pathogens?
Resp tract- bordetella pertussis, haemophilus influenzae
Urinary tract- some e.coli strains, Klebsiella pneumoniae
GI tract- vibrio cholera, shigella dysentriae, some e.coli strains, campylobacter jejune, helibacter pylori
51
Most common modes of infection by gram negative pathogens?
Meningitis: Neisseria meningitidis, haemophilus influenzae
STIs: Klebsiella pneumoniae, chlamydia trachoma's
Wound infections: pseudomonas aeruginosa, some e.coli strains
52
Features of fungal cells? What are dimorphic fungi?
Eukaryotic, chitinous cell wall
Heterotropic- gets nutrients from what they are living on
Yeast- small single celled organisms divide by budding
Moulds= from multicellular hyphae and spores
Some fungi exist as both yeasts and moulds switching between the two when conditions suit e.g. coccidioides immitis- grows as mould at ambient temp--> yeast form at body temp after inhalation
53
Fungi have inability to grow at what temp? Cannot evade what also? Burden of fungal disease?
37 degrees
Adaptive/ innate immune response
Enormous- most will have had at least one in lifetime e.g. nappy rash, tinea pedis and fungal asthma
Life-threatening fungal infection is rare in healthy hosts
54
Invasive fungal disease in immunocompromised hosts, post surgical patients and healthy hosts?
Immunocompromised= Candida line infections, pneumocystis, invasive aspergillosis
Post-surgical patients- intra-abdominal infections
Healthy hosts- fungal asthma, travel associated fungal infections e.g. dimorphic fungi
55
Aim of antimicrobial drug therapy? Relies on what?
Achieve inhibitory levels of agent site of infection with host cell toxicity
Identifying molecules with selective toxicity for organisms targets:
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
56
Why is selective toxicity harder to be achieved for fungi as opposed to bacteria? Drugs targeting DNA/ RNA synthesis and protein synthesis?
Fungi= eukaryotic and so are human cells, thus they are more similar and harder to differentiate
Flucytosine
57
Fungal cell wall contains what? Drugs targeting these?
| Plasma membrane contains what? Drugs targeting these?
Mannoproteins, B1,3 gluten, B1,6 gluten, chitin
Echinocandins
Ergosterol- cholesterol in humans
Amphotericin, azoles and Terbinafine
58
E.g. of a polyene? Polyenes cause what? What times lower affinity for cholesterol? Toxicities in humans?
Amphotericin B
Pore formation in ergosterol containing membranes i.e. its a fungicidal
x10 lower- more specific for fungi, can still cause toxicity to humans
Nephrotoxicity- dose dependent; usually reversible, distal renal tubular acidosis, can cause hyperkalaemia if infused rapidly--> cellular damage
Chills/ rigors/ hypotension and acute anaphylactoid reactions
59
E.g. allylamines? Causes what? Distributes extensively to where? Primarily used against what? Does result in what though?
Terbinafine
Reversible inhibition of squalene epoxidase (enzyme required for growth of fungi), its a fungicidal
Undergoes extensive first pass metabolism resulting in bioavailability of only 45%
Poorly perfused sites such as skin and nail beds
Candida and aspergillus
Well tolerated and only results in taste disturbance and deranged LFTs
CYP450 metabolism- by multiple enzymes and is minimally inhibitory
60
What are azaleas? E.g. and active against what x3?
Dose-dependent inhibitors of 14a-sterol demthylase- important in pathway cholesterol and ergosterol production
Clotrimazole and ketoconazole= candida
Fluconazole= cryptococcus
Itraconazole= aspergillus and dimorphic e.g. coccidiodes and sporothrix
61
Adverse events: all associated with? Rare to cause what? What with long term fluconazole? Itranazole symptoms?
```
Transaminitis and GI side effects
Relatively safe
Rare to cause severe hepatitis
Alopecia
GI symptoms more pronounced: nausea, abdominal pain and diarrhoea, rate life threatening liver failure
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62
Fluconazole is what so does what? Less significant interactions with what?
Hydrophilic so excreted unchanged
| Warfarin, calcineurin inhibitors, anxiolytics
63
Itraconazole is a potent what? Interactions with what? Azole resistance in what?
CYP3A4 inhibitor
Same as fluconazole, steroids, statins
Multiple mechanism in Candida, fluconazole and voriconazole most affected
64
Echinocandins inhibits what? What fungi generate that do not have large amounts of 1,3 B glucan in cell wall are intrinsically resistant to this drug class?
1,3B glucan synthase- interferes with fungal cell wall
Fungicidal to susceptible yeasts
Fungistatic to moulds
Crytococcus, zygomycetes, trichosporon, limited activity against Scedosporium
65
Echinocandins have activity against what? Has poor what and is only what? Has few what? What 3 limited drug toxicities?
Mould but not yeast forms of dimorphics
Poor oral bioavailability thus IV only
Poor penetration into CSF, eye and urine
Drug interactions
Rare type-1 hypersensitivity, hepatotoxicity, hypokalaemia
66
Blood cultures are half as sensitive for what? Better to pick-up from what? If what? Pretty much all what are sensitive to echinocandins? Also sensitive to what?
```
Fungi as for bacteria
Tissue/ fluids
If cultured properly, if these samples can be obtained
Candida
Amphotericin B
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67
1,3 B-D glucan is cell wall component of many fungi including what? Released into serum what?
Ascomycetous pathogens and pneumocystis
| Released into serum during invasive infection
68
Onychomycosis is what? Caused by what? Grow best at what temp? Most common cause? Most specific test?
```
Fungal infection of the nail
Very common
Dermatophyte moulds: grow best at about 30 degrees
Trichophyton rubrum
Microscopy- 30% culture negative
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69
Different forms of fungal differential diagnosis? Limited treatment options?
Psoriasis, lichen planus, trauma, eczema, malignant melanoma, results of sampling can be confusing
Topical amorolfine, systemic itraconazole or terbinafine
Treatment takes ages, high failure rate with all therapies
70
Pneumocystis infection of healthy people is what? Disease develops only with what? Signs of this infection?
Frequent and occurs early in life
Moderate-severe immunocompromised especially in HIV, transplant and steroids
Hypoxia more severe than chest X-ray would suggest- especially with gradual onset or risk factors
71
Treatment of pneumocystis? Why can fungi be challenging to treat?
Co-trimoxazole, clindamycin, pentamidine, trimetrexate
| Relatively few classes of agents effective against them
72
What is the single most effective method of preventing cross infection? What does infection require?
Hand hygiene
| Harm to be done to the individual- invasion, toxin, host response
73
What does CPE stand for? Also known as what? Colonisers of what? Most common causes of what? In past vast majority of these were what?
Carbapenemase producing enterobacteriaceae
Coliforms- standard gut germs i.e. e.coli, Klebsiella, Serratia, enterobacter
Large bowel, skin below waist and moist sites
UTI and intra-abdominal infection
Occasional resp tract infection and skin and soft tissue infection
Susceptible to antibiotics that we use for gram negative infection
74
What are carbapenems? They have moved from what to what?
Broadest spectrum beta-lactam antibiotics that we have available
Being rarely used last resort antibiotics to frequently used second-line agents and even first-line therapy for patients with severe sepsis as resistance of gram negatives to other agent like cephalosporins and piperacillin-tazobactam has increased
75
Carbapenemases hydrolyse what? What is an endogenous infection?
```
Carbapenems but also other beta-lactams effectively conferring resistance to entire class of antibiotic
Infection of a patient by their own flora- important in hospitalised patients, especially those with invasive devices or surgical patients
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76
Size of viruses? Only visualised using what? What does obligate intracellular mean? They have what?
20-220nm diameter, by electron microscopy
Dependent on living cells for their replication and existence
Receptor binding protein to dock to cells and all contain genetic material
77
When diagnosing don't need to come from where? Possess and don't possess what? 3 shapes of viruses? Exist as what outside of infected cells?
Sterile sites- no commensal viruses to confuse with
One type of nucleic acid/ RNA/ DNA, no cell wall structure but outer protein coat surrounded in some viruses by lipid envelope
Helical/ icosahedral/ complex
Virions- genetic material, protein coat (capsid)
78
What are the 6 stages of virus replication?
Attachment, cell entry, interaction with host cells, replication, assembly, release
79
E.g. of attachment via viral and cell receptors? Only what of virus are freed into host cell cytoplasm? What doesn't enter?
e.g. HIV= gp120, CD4 on T cell
Only viral 'core'- nucleic acid and some associated proteins acting as enzymes for replication and negation of intracellular host defence factors are freed
Outer protein coat does not enter
80
Involved in interaction of viruses with host cells? What is produced during replication of viral material?
Virus uses cell materials for own replication, also needs to subvert host cell defences
Progeny viral nucleic acid and viral proteins in nucleus, cytoplasm or both
81
Where does assembly occur for herpes, polio and influenza virus? How does release of viral material occur for rhinovirus and HIV/ influenza?
Nucleus- herpes, cytoplasm- polio, cell membrane- influenza
Rhinovirus= lysis, 'leaking'= HIV and influenza (2-3 days from upper resp tract)
82
5 ways in which viruses can cause disease?
Destruction of host cells e.g. polio
Modification of host cell e.g. rotavirus
Over-reactivity of immune system e.g. Hep B
Damage through cell proliferation e.g. HPV
Evasion of host defences e.g. i) cellular level e.g. herpes viridae
ii) molecular level e.g. influenza, HIV, rhinovirus
83
Types of polio and most severe? How does polio enter and cause disease?
3 types, type 1= most severe
Enters body orally then invades and replicates in gut then travels in bloodstream and targets brain, can destroy brain cells
Infection reaches brain in unimmunised person- difficult to deal with--> paralysis
84
2 forms of modification of host cell? Pathogenesis of how rotavirus causes disease by modifying host cell structure/ function?
Physical e.g. rotavirus/ HIV and functional e.g. rotavirus, RSV, HIV
1) Infects epithelial cells of small intestine- mainly jejunum
2) Atrophy of villi, flattening of cells, stripping of microvilli, decreased SA of SI
3) Limits synthesis of digestive enzymes
4) Nutrients not absorbed
5) Hyperosmotic effects--> profuse diarrhoea- need fluid replacement therapy, early treatment
85
Majority of HBV hep B infection is what? That and hep C spread by what? Following symptomatic HBV infection there are what? Results in what?
Asymptomatic
Blood/ sexual contact
Massive antibody and cell mediated immune (CMI) response, destroy many virally infected hepatocytes--> extensive liver damage--> jaundice
86
During acute hep B infection, large numbers of what are produced? If you recover (most do,) then you will be a what and what % asymptomatic?
Infectious HBV particles
Carrier and 80% will be asymptomatic
87
In chronic 'steady-state' carrier state of HBV, there is what?
Steady state between virus replication in host cells and host defence responses
Limited but sustained viral replication, natural hepatocyte regeneration, proliferation of hepatocytes due to oncogenic properties of HBV, liver cell destruction by CD8+ T cells that recognise HBV proteins on hepatocyte surface as 'foreign'
No clinical symptoms but HBV particles circulate in bloodstream
88
Features of HPV virus?
Causes plantar warts, can result in cancers- particularly those of cervix
No envelope compared to influenza, hep B or C, very small
70-80 different viruses, only type 16 and 18 have oncogenic potential in humans
89
Cervical carcinoma result of what? Once here virus may what and at some point may become what? What increases the change of integration?
HPV infection of supra basal layer in genital tract
Partially replicate including transcription and expression of several early viral gene products
HPV genome--> host cell chromosome
Mutagenic agents such as nicotine
90
4 diseases that have virus persistence? 4 that have virus variability? 2 mechanisms for viral evasion of host defences?
Herpes (throughout lifetime,) hep B and C viruses, measles virus, HIV
Influenza, HIV, hep C virus, rhinovirus
At cellular and molecular level
91
Viruses that have persistence/ latency? Cell to cell spread? Viruses with antigenic variability? Prevents host cell apoptosis?
All herpes viruses, varicella-zoster virus, Epstein-barr virus- causes glandular fever (latent in B cells meaning you carry virus for rest of life and can transmit via oral secretion)
Measles, HIV
Influenza type A virus, HIV, rhinovirus
Herpes, HIV- release proteins to prevent this and is thus able to continue to replicate
92
Viruses that interfere with host cell antigen processing pathways? Variation through forming quasi-species? Through gene re-assortment and mutation? Through many stable serotypes?
Herpes, measles, HIV
HIV, hep C virus
Influenza type A and HIV
Rhinoviruses- about 110 different cold viruses
93
Features of protozoa? Main biological role? Eaten by what and all eat food by what? 5 groups of protozoa?
Microscopic unicellular eukaryotes, over 50,000 species, can be free living or parasitic
Consumers of bacteria, algae and microfungi
Eaten by invertebrates, eat food by phagocytosis and then digest it in intracellular vacuoles
Amoebae, ciliates, sporozoa, flagellates, amoeboids
94
Flagellates have what and usually reproduce by what? E.g. of intestinal flagellate? Presentation of symptoms?
Flagellum, usually reproduce by binary fission
Giardia lamblia
Trip to India 2 months ago, loose stools on last day of stay in India, ongoing offensive diarrhoea daily since return to UK
Flatulence abdominal cramps
95
E.g. of haemoflagellates? Also known as what? Presentation of symptoms? Which strain more severe than more endemic East African strain? Other body sites? Name of lesion?
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Trypanosoma spp.
Sleeping sickness
Bitten on arm by insect, lesion 2 weeks later, 2 years later= fever, lethargy, myalgia, excessive weight loss, personality change, irritability, increasing daytime tiredness, coma
West African= more severe
Trichomonas vaginalis
Chancre
```
96
Amoebae move by what means? Presentation of amoebiasis?
Means of flowing cytoplasm and production of pseudopodia e.g. entamoeba histolytica
2-month visit to rural Botswana, bloody diarrhoea, on return to UK= increasing right upper quadrant pain, CT= liver abscess
97
Movement by sporozoans and reproduced by what? E.g.s? Presentation of toxoplasmosis?
No locomotory extensions, all species= parasitic, most= intracellular parasites
Reproduce by multiple fission
Malaria- plasmodium spp.
Other= cryptosporidium spp. and toxoplasma gondii
Ingestion of contaminated food and water/ feline faeces
Headaches and visual disturbances, commonly presents when people= immunosuppressed e.g. HIV/ AIDs or cancer on chemo
98
2 types of nucleus in ciliates? E.g. and presentation? Features of microsporidia?
Macronucleus and micronucleus e.g. balantidium coli- mainly those immunocompromised
Causes severe diarrhoea and or ulceration of colon
Very small, production of resistant spores, causes diarrhoea in immunocompromised e.g. enterocytozoon bieneusi
99
Malaria is a protozoan infection caused by what? 4 species that cause human disease? Transmitted by the bite of what? Presentation tends to occur within how long for falciparum? Incubation period of up to what for some species?
Plasmodia spp.
P.falciparum (most common,) p.ovale, p.vivax and p.malariae
Female anopheles mosquito
A month
Up to 1 year
100
Increasing incidence why? Female mainly bites when? Infection acquired from what?
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
At night
During feeding from infected human, mosquito= infected for life
101
Life span of female mosquito? Mainly bites where and lifecycle depends on what? Variation in what between different plasmodia spp. results in different clinical manifestations?
3-4 weeks
Indoors, lifecycle depends on water
Variation in lifecycle
102
How does female anopheles mosquito become infected? Developmental cycle usually takes how many days? What is the liver stage of the malaria lifecycle?
After taking blood meal containing gametocytes- sexual form of the malarial parasite
7-20 days- depending on temp--> migration of infective sporozoites to insect's salivary glands
Sporozoites--> new human host--> liver if not destroyed by immune system
Multiply inside hepatocytes as merozoites= pre-erythrocytic sporogeny
Few days= infected hepatocytes (schizonts) rupture releasing merozoites into blood- taken up by RBCs
103
Which 2 species remain in the liver as dormant as hypnozoites? Change to what from merozoites inside red cells? Then what happens? Each cycle of this process takes how long? In p.malariae however?
Vivax and ovale
Trophozoites to schizont and appear as 8-24 new merozoites
RBCs rupture- releasing trophozoites etc= immature trophozoites--> gametocytes
48 hours
72 hours
104
P.vivax and p.ovale attack what? P.malariae attack what? P.falciparum? A few merozoites will not develop into what but into what? Not released from what until taken up by what? What stage causes fever?
```
Reticulocytes and young erythrocytes
Older cells
Any stage of erythrocyte
Not trophozoites but into gametocytes
Feeding mosquito to complete life cycle
Blood stage- not liver stage
```
105
Anaemia from malaria due to what? What can happen in p.falciparum malaria?
Haemolysis of infected red cells, haemolysis of non-infected red cells, splenomegaly, folate depletion
Red cells containing schizonts adhere to lining of capillaries in brain, kidneys, gut, liver and other organs- can rupture, releasing toxins and stimuating further cytokine release
106
Other common features of 4 species of malaria? What is rosetting? Sequestration in small vessels including brain, lung can cause what?
Fever common, not always present
Other common: chills and sweats, headache, myalgia, fatigue, nausea and vomiting, diarrhoea
'Knobs' on RBC surface bind to receptors on endothelial cells in capillaries and venules, bind to non-infected RBCs
Tissue hypoxia
107
What % of red cells infected= indicator of severe disease?Cerebral malaria marked by what? Blackwater fever due to what?
High parasitaemia- more than 1% of red cells infected
Diminished consciousness, confusion and convulsions progressing to coma and eath- due to reduced brain perfusion caused by schizonts adhering to endothelial cells of capillaries
Widespread intravascular haemolysis affecting parasitised and unparasitized red cells giving rise to a dark urine
108
Symptoms in adults? Children?
Coma, ARDS, anaemia, jaundice, hepatosplenomegaly, hypoglycaemia, blackwater fever, renal failure, shock secondary to bacterial sepsis
Stop crying, playing, eating, tachypnoa- rapid breathing, anaemia, hypoglycaemia, cerebral malaria, raised intracranial pressure, convulsions, rule out meningitis
109
How to diagnose malaria? What does thick film do? Thin film? How many films should be examined before malaria is declared unlikely?
Do film at least 12 hours apart to check for presence of parasite
Sensitive but low resolution, tells you malaria is present
Can identify morphological features and quantification of parasitaemia, tells you type and parasite count- above 2%= severe
3 separate films
110
Treatment of complicated falciparum malaria? Uncomplicated falciparum malaria? Non-falciparum malaria? P.vivax and p.ovale malaria?
IV artesunate (gold standard) or IV quinine- causes hypoglycaemia so monitor sugar levels
Oral riamet or oral quinine, add doxycycline as 2nd agent to treat untreated malaria
Oral chlororoquine
Primaquine for hypnozoite clearance
111
What genetic trait gives protection against malaria? What deficiency can lead to haemolytic anaemia? What can also results in semi-immunity?
Sickle cell trait
G6PD- malaria parasites cannot survive in these red cells
Recurrent infection- lost if not reinfected after couple of years
Maternal transmission of antibodies across placenta- diminishes over time
112
3 key attributes of a pathogen? What are virulence factors?
Infectivity- ability to become established in host
Virulence- ability to cause disease once established
Invasiveness- capacity to penetrate mucosal surfaces to reach normally sterile sites
Microbial factors that cause disease
113
3 features of viruses? In humoral response- 4x forms of defence?
Need rapid cell entry, free virus in blood stream is easily neutralised, infected cells= destroyed
IgA= blocks binding, IgM= agglutinates particles, makes them difficult to enter cells, complement- opsonisation and cell lysis, antibodies- neutralise toxins
114
2 forms of cell-mediated response to viral infections? How many days post infection does cytotoxic T lymphocyte activity increase? Peaks at how many days then declines? Cytotoxic T cells eliminate what?
Interferon from Th or Tk cells= antiviral action, indcues anti-viral protein DAI on nearby cells
Cytotoxic T lymphocytes kill infected cells- so any virus in cell cannot replicate
3- 4 days, 7-10 days
Virus infected cells and so sources of new viral products eliminated
115
E.g. of where viruses cause direct cell cytoxicity?
Influenza virus to resp epithelium, varicella zoster virus to skin cells, yellow fever virus to liver cells, HIV to CD4 T-cells
116
Bacteria enter host via what 3 things? Number of organisms and virulence as well as location determine what?
Resp and GI tract, skin/ mucous membrane break e.g. wound
Defence mechanism employed:
low number/ virulence= phagocytes active, high= immune response, extracellular bacteria= antibody response, intracellular bacteria= cellular response
117
Bacteria compete with host cells and colonising flora by doing what? What do adhesins help bacteria to do and different types?
```
Sequestering nutrients, using novel metabolic pathways, out-competing other microorganisms
To bind to mucosal surfaces
Fimbriae and pili filamentous proteins
Non fimbrial proteins
Lipid
Glycosaminoglycans
Lectins of viruses and parasites
Miscellaneous viral capsids
```
118
What is secreted as part of a biofilm? Helps protect against what? Seen in what? 3 examples?
Extracellular polymeric substance of proteins, polysaccharides and DNA
Antimicrobials
Dental plaque, prosthetic materials and in otitis media
S.aureus, streptococcus mutans, pseudomonas aeruginosa
119
Neisseria e.g n.gonorrhoea secrete what? B.pertussis secrete? S.pneumoniae has what? Streptococci pyogenes release what that inhibits phagocytosis? Staphylococci produce what? Pseudomonas secrete what which inhibits C3a and C5a? Mycobacterium escape from and live where?
Proteases which lyses IgA
Adhesion molecules
A polysaccharide capsule that prevents phagocytosis
M protein
Coagulase that forms a fibrin coat round the organism thereby protecting it
Elastase
From phagolysosome and live in cytoplasm
120
Immune response and its effectiveness against protozoa depends on what? In blood what immunity, in tissue what immunity? Production of what may cause malaria symptoms? Antibody produced to what only poor response?
Location of parasite in host
Blood= humoral, tissue= cell mediated
Cytokines e.g. TNF
Sporozoites- only present in blood for short time
121
Features of infection with helminths? Process of schistosomiasis?
Multicellular organism- do not multiply in humans, not intracellular, few parasites carried, poor immune response
Snail--> larvae--> human--> liver--> intestinal mesentery (bladder veins)--> male and female--> eggs--> faeces/ urine--> snails
122
What isn't sufficient enough to kill worms? What is produced? What causes eosinophil production and mast cell growth? What is toxic to worms? How do adult worms evade the immune system?
Immune response
IL5 and IL3
Eosinophil basic protein
Decreased antigen expression by adult worms
Glycolipid/ glycoprotein coat= host derived so not perceived as foreign to immune system- utilises host self antigens
123
Within inflammation, upregulation of adhesion molecules is done on what 3 things? 2 things involved in chemotaxis? 4 things involved in degranulation? 2 things involved in vascular permeability? Vasodilation?
```
Monocytes, neutrophils, endothelia cells (IL-1, TNFa)
IL-8 and C5a
IL-8, C5a, IFN gamma, LPS
Prostaglandins, leukotrienes
Prostaglandins, leukotrienes, kinins
```
124
Antibiotics produced by what? Most agents are what? More correct term? Include what? Work by binding to what?
Microorganism
Semi-synthetic derivatives of antibiotics
Antimicrobials
Antifungals, antibacterials, anti-helminthic, anti-protozoal and antiviral agents
Target site on a bacteria
125
What do Beta-lactams target? Includes what bacteria groups? MRSA has what resistance and is thus resistant to what?
Bacterial cell walls
Penicillins, cephalosporins, carbapenems, combinations (B lactam inhibitor/ B lactam)
Flucloxacillin, Beta lactams
126
Beta lactams bind covalently to what? What are also active against PBPs? Target what in cell wall and what bacteria in particular? Cephalosporins target what bacteria well?
Penicillin binding proteins (PBPs)
Glycopeptides
Peptidoglycan- gram positive
Gram negative
127
What does benzylpenicillin (IV) have activity against? Used for? What bacteria is resistant?
Streptococci e.g. S.pneumo, beta-haemolytic streps (A,B,C,G), some other gram positive bacteria including clostridia
Skin and soft tissue infections e.g. endocarditis
Narrow spectrum
Enterococci= resistant
128
Phenoxymethylpenicillin (oral) is used against what? Amoxicillin (IV and oral) activity against what and greater than what? Uses?
Bacterial pharyngitis- 'strep throat' and splenectomy prophylaxis
Greater than benzylpenicillin
H. influenza, enterococci, enterobactericae- E.coli, proteus, shigella
Pneumonia, skin and soft tissue infection, UTIs
129
Flucloxacillin (IV and oral) activity against what? What are beta lactamases? What do beta lactamase inhibitors resemble and bind to beta lactamase to do what? E.g. x3?
Staphylococcus aureus
Enzymes produced by bacteria that hydrolyse penicillins and make them resistant
Traditional B-lactam antibiotic e.g. penicillin
Bind to B-lactamse and protect the antibiotic from degradation
Clavulanic acid, sulbactam, tazobactam
130
2x e.g. of B-lactams and B-lactamase inhibitors? E.coli resistant but sensitive to what?
Amoxicillin and clavulanic acid= co-amoxiclav (augmentin)
Pipercillin and tazobactam= Pipercillin/ tazobactam (tazocin)
Amoxicillin, amoxicillin and clavulanic acid
131
Cephalosporins are good for people with what allergy? E.g. of 1st, 2nd and 3rd generation cephalosporins? Used to treat what, but what are resistant?
Penicillin
Cefalexin, cefuroxime, ceftraixone, cefotaxime (penetrates CNS)
Meningitis
C.difficile and enterococci
132
E.g. of a monobactam? Given how? Activity?
```
Aztreonam- IV
Only gram negative rods/ bacilli
Safe for those with penicillin allergies
Has lower C.difficile risk
Narrow spectrum of activity
```
133
3x e.g. of carbapenems? Activity? Uses? Resistance from?
Meropenem, ertapenem, imipenem
Extended spectrum B-lactamases, ampC B-lactamases
Hospital acquired infection
Broad spectrum, cover resistant gram negatives
Expensive and C.difficile risk
Carbapenemase producing enterobactericae
134
E.g. of glycopeptides? Activity? Uses?
```
Vancomycin, teicoplanin
Gram positive only- cell wall
MRSA and other serious infections
People with penicillin allergy
Must monitor nephrotoxicity- more for vancomycin
Some resistance possible- VRE
```
135
E.g. of macrolides? Activity? Use?
Clarithromycin, erythromycin
Inhibit protein synthesis
Gram positives- e.g. S.aureus, atypical pneumonia pathogens as well as group A strep
Severe pneumonia, penicillin allergic patients, MRSA
Risk of C.difficile as well as resistance
136
E.g. of lincosamides? Activity? Use?
```
Clindamycin
Inhibits protein synthesis
Gram positives e.g. S.aureus, anaerobes and group A strep Cellulitis (if allergic to penicillin), necrotising fasciitis, MRSA
Good oral bioavailability
C.diff risk
```
137
E.g. of tetracycline? Activity? Use?
Doxycycline- oral
Inhibits protein synthesis
Broad spectrum
Cellulitis (if patient penicillin allergic), MRSA, possibility of resistance
138
E.g. of aminoglycosides? Activity? Use?
Gentamicin- IV, inhibits protein synthesis
Broad spectrum, enterobactericae, staphylococci, synergistically to treat strep
UTIs, infective endocarditis
Against extended spectrum B-lactams and AmpC B-lactams
Requires monitoring due to nephrotoxicity
139
E.g. of oxazolidinones? Activity? Use?
Linezolid
Inhibits protein synthesis
Gram positive e.g. MRSA, VRE
Serious/ gram +ve e.g. skin and soft tissue
Good oral bioavailability and penetration
Multiple side effects and interactions
140
E.g. of quinolones? Activity? Use?
```
Ciprofloxacin- IV and oral
Gram negatives more than gram positives
UTIs, penicillin allergy patients
Poor strep activity
Good oral bioavailability
Can be used against extended spectrum B-lactams and AmpC B-lactams
C.diff risk
```
141
Metronidazole inhibits what? Activity? Use?
```
Nucleic acid
Anaerobic bacteria
Intra-abdominal infection
Good oral bioavailability
Cheap
Emerging resistance
```
142
Trimethoprim inhibits what? Activity? Use?
```
Folate inhibitor
Broad spectrum
UTIs
Against extended spectrum B-lactams
Cheap, however increasing resistance
```
143
E.g. of pseudomonas? Anti-pseudomonal antibiotics?
```
Pseudomonas aeruginosa
Hospital acquired infection
Inherent resistance mechanisms
Pip/ tazobactam
Ceftazidime
Aztreonam
Gentamicin
Ciprofloxacin (only oral option)
```
144
Antimicrobials known as what? Produced by what, so what isn't an antimicrobial? Target site of bacteria known as what?
Agents produced by micro-organisms that kill/ inhibit the growth of other microorganisms in high-dilution
Micro-organism so gastric juice is not anti-microbial
Points of biochemical reaction crucial to survival of bacterium
145
Target of beta-lactams and glycopeptides? Of metronidazole and rifampicin? Fluroquinolones? Aminoglycosides, tetracyclines, macrocodes and chloramphenicol? Sulphonamides and trimethoprim?
PBPs on cell wall
Interfere with nucleic acid synthesis/ function
Inhibit DNA gyrase- needed for DNA replication
Inhibit ribosomal activity and protein synthesis
Inhibit folate synthesis- needed for bacterial growth, folic acid cannot cross cell wall
146
Antibiotics can be either what or what?
Bactericidal- kill the bacteria, more than 99% in 18-24 hours, generally inhibit cell wall synthesis, useful if poor penetration or difficult to treat infections
Bacteriostatic- prevent growth, but not necessarily kill it
More than 90% killed in 18-24 hours
Inhibit protein synthesis, DNA replication or metabolism
147
The lowest what is not always the best antibiotic? Drug must also what other than attaching to its binding target? To work effectively they must do what? Two major determinants of antibacterial effects?
Minimal inhibitory concentration (MIC)
Occupy adequate number of binding sites- related to its conc within the microorganism
Remain at binding site for sufficient period of time for metabolic processes to be sufficiently inhibited
Concentration and time that antimicrobial remains on binding sites
148
Conc dependent killing known as what? Key parameter is what? 2x e.g.s? Time dependent killing known as what? Key parameter and examples?
'Knockout punch'
How high conc is above the MIC
Aminoglycosides, quinolones
Sustained killing
Time that serum concs remain above MIC during dosing interval e.g. beta lactams, clindamycin, macrolides, oxazolidinones
149
Antibiotic must reach and stay where? 4 features of pharmokinetics?
Site of bacterial infection- depends on pharmokinetics
Release from dosage form
Absorption from site of administration into bloodstream
Distribution to various sites of body, including site of action and rate of elimination from body via metabolism (liver) or excretion (kidney) of unchanged drug
150
Distribution of drug depends on what? Half-life and elimination depends on what? 2 classes of consideration when administering antibiotics?
pH, lipid solubility
Dosage interval/ duration
Site of infection: which ones will penetrate site, pH, lipid soluble?
What antibiotics are safe: intolerance, allergy, anaphylaxis, side effects, age, renal and liver function, pregnancy and breast feeding, drug interactions, risk of clostridium difficile
151
In general any antibiotic beginning with what--> clos. difficile? 4 main ways a bacterium can resist antibiotics?
C e.g. ciprofloaxcin, clindamycin, cephalosporins, co-amoxiclav, carbapenems
Target site mutation, destruction of antibiotic, prevention of antibiotic entry or remove antibiotic from bacterium
152
2 examples of target site mutation?
Bacteria changes molecular configuration of antibiotic binding site/ masks it
e.g. Flucloxacillin cannot bind to PBP of staph in MRSA
Wall components change in enterococci and reduce vancomycin binding- vancomycin-resistant enterococci
153
2x example of antibiotic being destroyed? Preventing antibiotic entry?
Beta lactam ring hydrolysed by beta lactamase- cannot bind to PBP
Staph produce penicillinase- penicillin but not flucloxacillin is inactivated
Bacterial membrane porin channel size, numbers or selectivity= modified
154
How can antibiotics be removed from bacteria?
Proteins in membrane can act as efflux pump/ export so antibiotic is pumped out e.g. s.aureus/ s.pneumoniae resistance to fluroquinolones, enterobactericae resistance to tetracyclines
155
2 methods of resistance development?
Intrinsic natural resistance- all subpopulation of species= equally resistant e.g. aerobic unable to reduce metronidazole to its active from so is harmless
Anaerobic lack oxidative metabolism required to uptake aminoglycosides
Vancomycin not taken up by gram negative- cannot penetrate outer membrane since too large
Acquired resistance- only certain strains/ subpopulations of species will be resistant
156
2 ways of acquired resistance? 3 methods of horizontal gene transfer?
Spontaneous gene mutation- new base pair, change in amino acid sequence, enzyme/ cell structure, reduced affinity or antibiotic activity
Horizontal gene transfer- conjugation, transduction, transformation
Conjugation- sharing of extra chromosomal DNA plasmids
Transduction- insertion of DNA by bacteriophages
Transformation- picking up naked DNA
157
Gram positive: MRSA contains what gene that encodes PBP2a that does not bind penicillin? Confers resistance to all what? VRE has acquired resistance how? Promoted by what?
SCCmec contains resistance gene mecA
Beta-lactam antibiotics in addition to methicillin
Plasmid mediated of gene encoding altered amino acid on peptide chain preventing vancomycin binding
Cephalosporin use
158
Gram negative: B-lactamase produced by E.coli, H. influenza and N. gonorrhoea? By K. pneumoniae? Such strain typically remain sensitive to what?
TEM-1, SHV-1
| Beta-lactamase inhibitors
159
Extended spectrum B-lactamases have further what? They can also inactivate what?
Mutation at active site- can destroy more than just penicillin or amoxycillin
Cephalosporins
Combination antibiotics
160
AmpC B-lactamse has broad spectrum resistance against what? 2 bacteria with B lactase inhibitor resistant? Can be treated with what, but may require what?
Penicillin, cephalosporins and monobactam resistance
Citrobacter spp. and enterobacter spp.
Quinolones or trimethoprim
Carbapenem treatment or agents such as fosfomycin/ temocillin (UTIs and chest infections)
161
6 mycobacteria with medical importance?
```
M.tuberculosis- TB
M.leprae- leprosy
M.avium complex (MAC)- disseminated infections in AIDs, infections in patients with chronic lung disease
M.kansasli- chronic lung infection
M.marinum- fish tank granuloma
M.ulcerans- Buruli ulcer
```
162
Features of mycobacteria? High cell wall content of what? Weakly what and what why? Survive inside what?
Aerobic, non-motile, non-spore forming, bacillus/ rods, may cause meningitis, can withstand phagolysosomal killing
High molecular weight lipids and lipoarabinomannan
Gram-positive or colourless since they have a thick cell wall
Macrophages- even in low pH environments
163
Rate of mycobacterial growth? This means what? Cell wall key components?
Slow growth- M. tuberculosis= 15-20 hours compared to 1 hour for common pathogens
Difficult for antibiotics to target the division phase of the mycobacteria
Mycololic acids and liporabinomannan- make strong waxy cell wall that is hard for immune system to target/ damage
164
4 Koch postulates?
Bacteria should be found in all people with disease
Bacteria should be isolated from infected lesions in people with disease
Pure culture inoculated into susceptible should produce symptoms of disease
Same bacteria should be isolated from intentionally infected individual
165
What makes mycobacteria resistant to gram stain? Turns Ziehl- Neelsen stain what colour? Positive for what?
High lipid content with mycolic acids in cell wall makes mycobacteria
Slightly curved, beaded bacilli
Red/ pink- positive for acid- fast
166
Nucleic acid detection amplification using what? Recommended for what?
PCR
Rapid result for mycobacterium tuberculosis
Highly sensitive and specific test
For rapid diagnosis in TB endemic countries
167
Aim to withstand phagolysosomal killing and escape to cytosol how? Host aims to kill how? CD4 T-cells generate what which helps to activate intracellular killing by macrophages? What from macrophages further stimulates generation of Th cells and interferon gamma release? What can lead to susceptibility to infection?
Thick waxy cell wall
Using microbicidal molecules
Acidification aids digestion and degradation by proteases of mycobacteria which results in generation of antigens for presentation to T-cells
Interferon gamma
IL-12
Genetic defects in interferon gamma or IL-12 receptors
168
What are granulomas? They highly stimulate macrophages to become what? Some fuse with each other to form what? What cells infiltrate this? Central tissue may what?
Lesions that arise in response that tries to contain mycobacteria
Epithelioid cells
Giant multinucleate cells 'Langhans giant cells'
T cells including cytotoxic CD8 T-cells
Necrose and form a caveating granuloma- lung--> cavity
169
Granuloma prevents what from entering? What goes into dormant state? Highly immunogenic nature of mycobacterial lipids stimulate T-cell responses how many weeks after exposure to M.tuberculosis? Positive and negative effects?
Nutrients- starves mycobacteria
TB- can reactivate at some point in future when conditions are better
3-9 weeks
Macrophage killing of mycobacteria, containment of infection, formation of tissue granuloma
Hypersensitivity reactions (type 4)- skin, eye lesions and swelling of joints
170
Hypersensitivity like this can measure in what 2 ways?
Tuberculin skin test- intradermal injection of purified protein derivative--> skin swelling and redness
Interferon gamma release assays
171
Principles of mycobacteria treatment?
Slowly replicating- need prolonged treatment- 6 months of antimicrobials
Different pops in particular locations intracellularly and extracellularly/ in environments of differing pH
Multi-drug combinations to ensure target all populations and mutants
Observed treatment to ensure compliance and success
172
3 different types of TB? In primary TB, bacilli settle where and taken in what? In apex more and less what? 3 things within primary complex?
```
Primary, latent and pulmonary TB
In apex and granuloma forms
In lymphatics to hilar lymph nodes
More air and less blood supply- fewer defending white cells to fight off infection
Granuloma, lymphatics and lymph nodes
```
173
What type of immune response in latent TB? What is contained and what persists?
Cell mediated (CMI) response from T cells
Primary infection contained, but CMI persists
No clinical disease- normal CXR
Detectable CMI to TB on tuberculin skin test of IGRA
174
Pulmonary TB could occur when? Features?
Immediately following primary disease (post-primary) or after latent reactivation
CMI 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
175
Bacilli can spread from where to where and elsewhere? Where else?
```
From apex to hilar lymph nodes
TB meningitis
Miliary TB- widespread dissemination and tiny spotted lesions all over lungs and elsewhere
Pleural TB
Bone and joint TB
Genitourinary TB
```
176
What is HIV? Two markers used to monitor HIV infection? 3 stages of HIV infection (on graph)?
Lentivirus that uses reverse transcriptase to replicate (retrovirus)
CD4 cell count and HIV viral load
1) Acute primary infection- fall in CD4 count followed by gradual rise. Acute rise in viral load- then fall to 'set point'
2) i) Asymptomatic phase- progressive loss of CD4 cells, clinical latency
ii) Early symptomatic HIV: AIDs related complex
3) AIDs- symptoms of immune deficiency- CD4< 200
177
Rash in acute HIV is what? Long-term non-progressors? Rapid progressors? AIDs typically how many years?
Symmetrical maculopapular rash (raised red lumps)- can involve whole body (face, palms and soles too)
Host and viral genetic factors, HIV-2- no signs or symptoms after at least 7 years infection with CD4> 600 cells/ ml in absence of treatment
Elderly and children, high viral load
5-10 years
178
Infections due to HIV?
```
Candidasis: oesophageal/ lung
Extra- pulmonary cryptococcosis
Cryptosporidosis> 1 month
CMV: any organ except liver, spleen, lymph nodes
Mycobacterium TB
Toxoplasmosis of internal organs
HSV with muco-cutaneous ulcer> 1 month
Pneumocystis jiroveci (carinii) pneumonia (PCP)
Recurrent bacterial pneumonia
```
179
Neoplasms due to HIV? Direct HIV effect?
Invasive cervical carcinoma, Kaposi's carcinoma, primary CNS lymphoma, non-Hodgkin's lymphoma
HIV dementia/ encephalopathy, HIV associated wasting
180
Features of primary HIV infection?
```
Exposure to symptoms 2-4 weeks, max 10 months
Abrupt onset of non-specific symptoms
Can be severe- 2 weeks
Weight loss can occur
Lethargy/ depression can last months
Aseptic meningitis
Severe symptoms with rapid progression
```
181
3 things to do with patient with fever, rash and non-specific symptoms? Most antibody positive by how many weeks? Viral load steady state how many months after?
1) Take sexual history 2) Think of HIV seroconversion illness 3) Tell lab- check for antigen as well
Think of testing for HIV infection when faced with recurrent shingles, candidiasis etc.
4-10 weeks
4-6 months
182
Clinically latent phase?
No findings apart from PGL: persistent generalised lymphadenopathy
Enlarged lymph nodes involving at least 2 non-contagious sites other than inguinal nodes
183
Symptoms of early symptomatic HIV?
```
Oral/ vaginal candida
Oral hairy leukoplakia
Cervical dysplasia
Cervical carcinoma in-situ
Peripheral neuropathy
```
184
3 HIV drugs used? HAART involves what 3 drugs commonly? Aim to do what?
1) Reverse transcriptase inhibitors- nucleoside and non-nucleoside
2) Protease inhibitors
3) Fusion inhibitors
2 NRTI and 1 NNRTI or 2 NRTI and 1 PI
To reduce VL< 50 copies/ ml and increase CD4 count
185
What are the UNAIDs 90/90/90 goals? Epidemic is largely among who?
Global target of 90% of people living with HIV being diagnosed, 90% diagnosed on ART, 90% viral suppression for those on ART by 2020
Men that have sex w/men, those that don't use condoms, have other STIs, having multiple simultaneous partners, IVDU, uncircumcised man
186
Transmission of HIV? Resp disease in HIV?
Blood products, sex, vertical (mother to child), IVDU, needle stick injuries, organ donation
Bacterial pneumonia, tuberculosis, apergillus, EBV, pneumocystis jiroveci pneumonia (PCP)
187
GI disease in HIV? CNS disease in HIV?
Oral candida, diarrhoea, perianal warts and ulcers
CNS mass lesions: cerebral toxoplasmosis, cerebral lymphoma, tuberculoma, cryptococcal meningitis, encephalopathy
Ophthalmic lesions: CMV retinitis
188
Methods of prevention?
Circumcision- removing foreskin= reduced ability of HIV to penetrate due to keratinisation of inner aspect of remaining foreskin
Contains Langerhans cells= prime target for HIV- some removed with foreskin
Likelihood of acquiring other infections= reduced
STI control, vaccines, microbicides, HIV diagnosis, HAART, partner notification, screen blood products, prevent needle exchange/ sharing drugs, preventing mother to child transmission by C-section for HIV+ve mothers and bottle feeding
189
Behavioural prevention for HIV?
Sex education, reduce freq of partner change, avoid concomitant sex partners, educate high risk sexual practices, consistent condom usage, reduce contact with people from high prevalence groups
190
Benefits of testing for HIV? Misconceptions of testing?
Access to appropriate treatment and care, reduction in morbidity and mortality, reduction in MTCT, reduction of sexual transmission, public health, cost-effective
Lengthy pre-test HIV counselling is not requirement unless pt requests
Negative HIV test does not need to be disclosed on applications for insurance
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3 types of tests?
Point of care tests- finger prick blood, convenient but has lower sensitivity and specificity and can give false positive and negative results
Venous blood samples/ serum or saliva ELISA test (ideal)- antibodies in serum detectable in >99% infected people 12 weeks post-exposure
4th generation HIV tests include IgM and p24 antigen reduces window period to <1 month= high sensitivity and specificity
Home testing kits- done in incubation/ window periods thus can lead to misdiagnoses/ inadequate partner notification
Sometimes failure to collect adequate sample, has huge public health impact
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What to do if negative test? What if positive or not clear? What to do if they don't tell their partner? Who should it be disclosed to?
Repeat if within 'window period'- period between exposure and when test will be accurate can be up to 3 months
Explain test ''reactive'' and needs further investigation, book appt where pt is diagnosed w/ serious communicable disease are told to inform sexual contacts- allows disclosure if at risk and unaware
Inform the pt that you are going to tell the sexual partner
The insurance company as it is blood-borne- not otherwise notifiable disease
193
HIV-1 and HIV-2 are 2 related retroviruses belonging to what and carry what? Capable of what? HIV-1 arose from what? HIV-2?
Lentivirus subfamily
Human endogenous retrovirus' which contain the true retrovirus- which is linked to the expression of tumour cells
Reverse transcription
Transmission of SIV cpz from chimpanzees to humans sometime pre-1950
From SIV sm separately- less virulent
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What enzyme integrates viral DNA into host cell DNA? 9 steps of replication?
Integrase enzyme
Attachment, entry, uncaring, reverse transcription, genome integration, transcription of viral RNA, splicing of mRNA and translation into proteins, assembly of new visions, budding
195
What does CD4 bind to? This interaction raises what? Mutations in what gene is responsible for 2 types of HIV resistance? 9kB RNA genome encodes what 9 genes? Which 4 genes are essential for infectivity?
gp120 on HIV
Antibodies that are detected when HIV test is done
CCR5
Gag, Pol, Env, Tat, Rev, Nef, Vif, Vpr and Vpu
Gag, Pol, Env, Tat, Rev
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What gene contributes to viral replication and enhances production of host transcription factors? What gene binds to viral RNA and allows export from nucleus and regulates RNA splicing? What gene increases infectivity? What gene encodes structural proteins, made as a poly protein and is cleaved by HIV protease?
Tat
Rev
Nef
Gag
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What gene encodes the enzymes: reverse transcriptase, integrates and polymerase? What gene encodes the envelope proteins? What gene disrupts host antiviral factors?
Pol
Env
Vif- prevents blocking of viral replication during reverse transcription
198
Which cells are depleted by HIV?
Naive and memory CD4 cells, macrophages also- affect innate defence of host
macrophages pass HIV onto T cells--> die and more HIV created into blood
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Mechanisms of CD4+ T-lymphocyte depletion?
Direct cytotoxicity of directly infected cells, activation induced death(apoptosis), decreased production, redistribution- trafficking of CD4+ T-cells from periphery to lymphoid tissue
Bystander cell killing, infection of CD34+ progenitors in bone marrow
200
Reservoirs of HIV replication?
Genital tract, CNS, gastrointestinal system, bone marrow, particular cells e.g. macrophages, microglia, resting T cells such as CD4+ CD445RO memory cells only support replication when activated
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Other aspects of immune dysfunction?
CD8+ T-cells= enhanced activation and decreased function
B-cells= enhanced activation and decreased proliferation resulting in increased non-specific Ab production
Decreased NK, neutrophil and macrophage function
Perturbed cytokine networks: reduced Th1 responses, increased Th2/ Th0
202
What do nucleoside reverse transcriptase inhibitors do? What do protease inhibitors do? Fusion inhibitors? Microbicidal gel?
Prevent HIV RNA becoming DNA- preventing it entering the nucleus
Prevent immature HIV becoming mature HIV thus slowing cell-to-cell spread
Prevent HIV envelope and CD4 cell membrane fusion
For vagina to decrease the risk of HIV transmission
203
Ascarius lumbricoides affects what % of the world's population? Worms are divided into what 3 groups?
25%
| Nematodes (roundworms,) trematodes (flatworms, flukes) and cestodes (tapeworms)
204
3x e.g. of roundworms? Trematodes are found in what 4 places? 2 types of tapeworm?
Intestinal, larva migrans, tissue (filiria)
Blood, liver, lung, intestinal
Invasive and non-invasive
205
Adult worms cannot usually reproduce without a period of what? Worm cannot replicate where? Although they usually produce innumerable larvae or eggs (which may themselves cause disease), total worm burden cannot increase without what?
Development outside the body
Inside the body- cannot get out will eventually die
Constant re-exposure to infection
206
Varicella zoster virus has what 2 diseases? When is person with chickenpox most infectious?
Varicella ''chickenpox''= primary infection
Herpes zoster (HZ) 'shingles'= secondary reactivation
From 1-2 days before the rash appears until all the blisters have crusted over
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Incubation period of chickenpox is about how long? Chickenpox is common in who? Is highly what? Usually benign but can be serious in what groups? % adults raised in UK have had chickenpox?
```
1-3 weeks
Childhood
Contagious
Immunocompromised and who have had transplants, adults, pregnant women, smokers, infants
90%
```
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5 stages of chickenpox? What distribution is a typical feature of chickenpox? Feature of lesions of chickenpox and measles compared to smallpox? Chickenpox info to collect?
Macule--> papule--> vesicle--> pustule--> crust
Centrifugal- greatest conc on face and distal extremities, first= oral mucosa, face or forearms
Age of pt, onset of rash, any contacts? Immunosuppressed? Pregnant?
209
How is chickenpox diagnosed?
Pop lesion with sterile needle (don't wipe with alcohol swab first,) absorb vesicle contents onto swab, replace swab in cassette and send for VZV/ HSV PCR
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Complications of chickenpox? Complications relatively rare in who?
Dehydration, haemorrhagic change, cerebellar ataxia (common,) encephalitis, varicella pneumonia- bacterial empyema, skin and soft tissue infection typically with group A strep, bone and joint infections: deep sepsis- osteomyelitis/ pyomyositis, congenital (foetal) varicella syndrome
Children- more common in adults
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Most common chickenpox complication in adults? Affects what % of adults? Risk x2 if what 2 things? % mortality if untreated? Mortality with adequate treatment?
```
Chickenpox pneumonitis
15%
Underlying lung disease/ smoker
30%
6%
```
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Foetal infection occurs in what % of cases of chickenpox in pregnancy? Is usually what 2 things? If any manifestations, what in 1st year of life? If maternal chickenpox in first 1/2 pregnancy, what % infants will develop FVS? Potential severe defects? FVS is very what?
```
10-15%
Transient and asymptomatic
Shingles
2%
Cicatricial skin scarring, limb hypoplasia, visceral and ocular lesions, microcephaly and growth retardation
Rare
```
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3x features of archived serum samples?
Blood sample, tube contains gel to separate cells from serum once centrifuged, small sarsted tubes kept for about 3 years
214
3 stages of viral dormancy of chickenpox?
Primary infection- widespread chickenpox--> viral dormancy in dorsal root/ cerebral ganglion--> localised reactivation- shingles
215
Shingles most common in who? Fraction of people over 70 who have shingles die of infection? Location of reactivation? % of cases ophthalmic?
Elderly
1/1000
Thoracic region (50-70% cases)
10-20%
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Thing to look out for with measles?
Fine maculopapular rash on trunk between day 3 and 5 of illness, spreads to face and extremities. Marked blanching
