Microbiology Flashcards

Question

What is an exotoxin?

Answer 1

Secreted proteins of gram positive and gram negative bacteria

Answer 2

Composition: Protien Action: Specific Effect of heat: Labile Antigenicity: Strong Produced by :Gram positive/ Gram negative Covertibility to toxoid: Yes

Answer 3

Composition: lipopolysaccharide Action: non-specific Effect of heat: stable Antigenicity: weak Produced by : LPS - gram negative Covertibility to toxoid: No

Answer 4

Toxoid is a toxin treated (usually with formaldehyde) so that it loses its toxicity but retains its antigenicity

Answer 5

Bacteria usually have one singular chromosome in a circle made up of DNA – have single RNA polymerase which makes messenger rna Typically 2-4 10 to the power of 3 kilobases

Answer 6

These can be transcribed and translated to make proteins Have point mutation in chromosomes Can be transferred around by different bacteria

Answer 7

Mutation -Base substitution -Deletion -Insertion Gene transfer -Transformation eg via plasmid -Transduction eg via phage – bacterium infected by virus -Conjugation eg via sex pilus

Answer 8

Please look at slide 49 of 'bacteria as a cause of disease' REMEMBER THIS PLEASE

Answer 9

Rickettsia -R. rickettsii -R. prowazekii -R. conorii Chlamydia -C. trachomatis -C. psittaci -C. pneumoniae Coxiella -C. burnetii These cannot be cultivated on media

Answer 10

Mollicutes Mycoplasma pneumoniae M. hominis Ureaplasma urealyticum

Answer 11

Growing as filaments and growing as single cells

Answer 12

Actinomyces - A. israelii Nocardia - N. asteroides Streptomyces

Answer 13

Rods Cocci Spirochaetes

Answer 14

Leptosira L. . icterohaemorrhagiae Treponema T. pallidum Borrelia B. burghdorferi B. recurrentis

Answer 15

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

Answer 16

Aerobic: STAPHYLOCOCCUS - S. aureus, S. epidermidis Streptococcus Anaerobic: PEPTOSTREP- TOCOCCUS

Answer 17

BETA-HAEMOLYTIC S. pyogenes (A) S. agalactiae (B) ALPHA-HAEMOLYTIC S. pneumoniae S. oralis S. milleri S. sanguis NON-HAEMOLYTIC S. bovis ENTEROCOCCUS E. faecalis (D)

Answer 18

MYCOBACTERIA M. tuberculosis M. leprae M. avium-intracellulare M. ulcerans M. kansasii

Answer 19

ANAEROBIC CLOSTRIDIUM C. perfringens C. tetani C. botulinum C. difficile PROPIONIBACTERIUM P. acnes Aerobic: AEROBIC CORYNEBACTERIUM C. diphtheriae etc LISTERIA L. monocytogenes etc BACILLUS B. anthracis B. cereus etc

Answer 20

Streptococcus

Answer 21

Staphylococcus

Answer 22

Alpha result: Alpha haemolytic strep ( viridans strep) Beta result: Beta haemolytic strep Antigenic group (A,B,C,G)

Answer 23

If its resistant then its viridians strep If its sensitive: S. penuomniae

Answer 24

Positive = S. aureus Negative = Coagulase negative staphylococcus

Answer 25

Coagulase: enzyme produced by bacteria that clots blood plasma.

Answer 26

at least 40 species: -‘Coagulase’ + ve or – ve Fibrin clot formation around bacteria may protect from phagocytosis. -Coagulase -ve species, e.g. S. epidermidis only important as opportunistic infections Normal habitat -nose and skin

Answer 27

Spread by aerosol and touch -carriers & shedders Virulence factors -Pore-forming toxins (some strains) -alpha - haemolysin -Panton-Valentine Leucocidin ‘PVL’ Proteases -Exfoliatin Toxic Shock Syndrome toxin -(stimulates cytokine release) Protein A -(surface protein which binds antibodies in wrong orientation)

Answer 28

resistant to major antibtiocis Beta-lactams gentamicin, erythromycin tetracycline

Answer 29

Due to a large range of virulence factors. This includes pore forming toxins. The PVL toxin is produced by many of the community MRSA strains and causes haemorrhagic pneumonia. It is encoded by a pro-phage gene that is incorporated into the bacterial genome.

Answer 30

Low concentration: induces apoptosis in cells by allowing exchange of monovalent ions across the cell membrane. High concentration: it binds to the lipid membrane and causes massive necrosis

Answer 31

S.epidermidis: -Infections are ‘opportunistic’ .immunocompromised, .prostheses -Main virulence factor - ability to form persistent biofilms S.saprophyticus: -Acute cystitis .haemagglutinin for adhesion .urease

Answer 32

Alpha- haemolysis is due to the production of hydrogen peroxide, which reacts with haemoglobin to form the green compound met-haemoglobin. Get partial greening S.penumoniae

Answer 33

Beta-haemolysis is due to the production of two pore-forming toxins – streptolysin O and S. Streptolysin O is oxygen sensitive and is very antigenic e.g. S.pyogenes

Answer 34

For Beta haemolytic strep only Carbohydrate cell surface antigens Lancefield Groups A-H and K-V Group A - S.pyogenes throat, skin, post partum Group B - S.agalactiae neonatal infections

Answer 35

Antiserum (antibodies) made that recognise each group Tagged to tiny plastic beads added to a suspension of bacteria Antibodies bind bacteria and beads clump together Visible to naked eye

Answer 36

Hyaluronidase - spreading Streptokinase - breaks down clots C5a peptidase - reduces chemotaxis

Answer 37

Toxins Streptolysins O&S -binds cholesterol Erythrogenic toxin -Streptococcal pyrogenic toxin e.g. SPeA – exaggerated response

Answer 38

Capsule - hyaluronic acid M protein – surface protein - M protein is an antiphagocytic protein and some strains carry a hyaluronic capsule layer, which is non-antigenic. (encourages complement degradation)

Answer 39

Respiratory -Tonsillitis & pharyngitis - most common Skin and Soft tissue -Impetigo -cellulitis Scarlet fever rheumatic fever

Answer 40

Normal commensal in oro-pharynx ~ 30% of population Causes - pneumonia, otitis media, sinusitis, meningitis Predisposing factors -impaired mucus trapping (e.g. viral infection) -hypogammaglobulinaemia -Asplenia -HIV

Answer 41

Capsule -polysaccharide (84 types), antiphagocytic .polysaccharide vaccine ‘PPV’ 23 types .conjugate vaccine ‘PCV’ 13 types Inflammatory wall constituents -teichoic acid (choline) -peptidoglycan Cytotoxin -pneumolysin

Answer 42

alpha- haemolytic (or non-haemolytic) Optochin resistant Some cause dental caries & abscesses Important in infective endocarditits -S. sanguinis, S. oralis Cause deep organ abscesses (e.g. brain, liver) Most virulent are the “milleri group” -S.intermedius, S.anginosus, S.constellatus Viridans streptococci is a term used to describe collectively the oral streptococci.

Answer 43

Listeria monocytogenes Bacillus anthracis (Anthrax) - spore forming Corynebacterium diphtheriae

Answer 44

Clostridia...: spore forming, survive in environment, produce toxins C. tetani Tetanus C. botulinum Botulism C. difficile antibiotic associated diarrhea pseudomembranous colitis

Answer 45

From infected wounds Toxin inhibit GABAs neurotransmission and cause muscle contractions and spasms progressing from head to body ‘Risus sardonicus ‘or rictus grin

Answer 46

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

Answer 47

LPS (‘endotoxin’) forms the outer leaflet of the outer membrane of G-ves, and comprises: 1.Lipid A, the toxic portion of LPS - anchored in the outer leaflet of outer membrane. 2.Core (R) antigen, short chain of sugars, some are unique to LPS. 3.Somatic (O) antigen, a highly antigenic repeating chain of oligosaccharides.

Answer 48

any product or strategy that contributes to pathogenicity/virulence 1.Colonisation factors: adhesins, invasins, nutrient acquisition, defence against the host 2.Toxins (‘effectors’): usually secreted proteins that cause damage, subversion

Answer 49

Family Enterobacteriaceae = more commonly termed “Enterobacteria”* Rods, most are motile (peritrichous flagella) – flagella over entire surface of bacteria Facultatively anaerobic Some species colonise the intestinal tract (in a good or bad way!) Family within proteobacteria Rod shaped and gram negative: most gram negative are rod shaped

Answer 50

H antigen (flagellum) O (somatic) antigen (LPS) K antigen (exopolysaccharide ‘capsule)

Answer 51

Antigenically distinct variants of a single species are referred to as ‘serovars’, i.e. E. coli O157:H7 (EHEC) and E. coli O45:K1:H7 (NMEC) are different serovars of E. coli.

Answer 52

Gives rise to antigenic variation among species AND between different strains of the same species.

Answer 53

Commensals - most abundant facultative anaerobe (107-108/g faeces) Peritrichous flagella

Answer 54

Wound infections (surgical) UTIs (cystitis; 75-80% ♀ UTIs - faecal source or sexual activity; catheterisation - most common type of nosocomial infection) Gastroenteritis Travellers’ diarrhoea Bacteraemia (sometimes leading to sepsis syndrome) Meningitis (infants) - rare in UK

Answer 55

Several ‘pathovars’ (distinct pathogenic strategies) Common ‘core genome’ (most genes are common to all strains/pathovars) Acquisition of pathogenicity genes ‘lateral gene transfer’

Answer 56

Very closely related to Escherichia (= “E. coli + a virulence plasmid”) Four species: S. dysenteriae, S. flexneri, S. boydii, S. sonnei

Answer 57

Pathology like Enteroinvasive Escherichia coli (EIEC) but with the addition of Shiga toxin Severe bloody diarrhoea (esp. S. dysenteriae) Frequent passage of stools (>30/d) pus and blood, prostrating cramps, pain in straining, fever Self-limiting (in adults)

Answer 58

Acid tolerant Person-to-person or contaminated water and food Entry through colonic M cells* (antigen sampling) Induced uptake M cells: overlie lymphoid follicles and deliver antigens to underlying immune cells.

Answer 59

Look at slide 21 of gram negative bacteria powerpoint Shigella bacteria enter M cell from apical surface of the lumen causing apoptotic macrophage to enter the cell and destroy M cell. More shigella bacteria enter enterocyte (intestinal epithelial cell) from basolateral surface after which causes translocating polymorphonuclear leukocytes to be recruited to site of infection causing further damage to epithelium.

Answer 60

Shiga toxin (Stx)

Answer 61

Think of one big circle in the middle which is A and 5 smaller cirlces around it which is B A is the catalytic subunit (glycosidase) and B is the receptor binding subunits It cleaves N-glycosidic bond of adenosine residue in 28S rRNA of the 60S subunit of the ribosome (depurination) > blocks EF-1 and EF-2 binding > protein synthesis inhibited > cell death

Answer 62

Targets kidney > microvascular thrombosis in kidneys > kidney failure

Answer 63

Two species: S. enterica - responsible for salmonellosis >2,500 serovars* S. bongori - rare (contact with reptiles)

Answer 64

1.Gastroenteritis/enterocolitis (serovars Enteritidis and Typhimurium) Frequent cause of food poisoning (milk, poultry meat & eggs) Second highest no. of food-related hospitalisations/deaths (UK) 6-36 hr incubation, resolves (~7 days) Localised infection, only occasionally systemic 2.Enteric fever - typhoid/paratyphoid fever (serovars Typhi and Paratyphi) 3.Poor quality drinking water/poor sanitation Systemic disease ~20 million cases, ~200,000 deaths/yr (globally) Bacteraemia (serovars Cholerasuis and Dublin) Uncommon

Answer 65

Ingestion of contaminated food/water - high I.D. (~106) unless in chocolate! (‘faecal-oral route’) 1.Invasion of gut epithelium (small intestine) 2.Transcytosed to basolateral membrane 3.Enters submucosal macrophages 4.Intracellular survival/replication

Answer 66

1.Bacterial-mediated endocytosis into M cell 2.Induction of interleukin-8 release from enterocyte> 3.Neutrophil recruitment and migration> 4.Neutrophil-induced tissue injury> 5.Fluid and electrolyte loss > diarrhoea 6.Inflammation/necrosis of gut mucosa Look at slide 26 gram negative bacteria

Answer 67

1.Bacterial-mediated endocytosis into enteric cell 2.Transcytosis to basolateral membrane of M cell 3.Survival in Macrophage >systemic spread 4. Migration to reticuloendothelial organs via lymphatics & blood Look at slide 26 gram negative bacteria

Answer 68

1. Ingestion of S.Typhi via bacterial endocytosis > 2. Enters small intestine > 3. Inflammation and ulceration of Peyer’s patches > 4. Diarrhoea; haemorrhage or perforation (1-3% of cases)#

Answer 69

1. Ingestion of S.Typhi via bacterial endocytosis > 2. Enters small intestine > 3. Travels from SI in lymphatic system within macrophages to Mesenteric lymph nodes 4. From mesenteric lymph nodes enters bloodstream via thoracic duct > 5. Goes to transient (primary) bacteraemia 6. Multiplication in macrophage in liver, spleen and bone marrow 7a. CAN travel from liver to gall bladder where it stays in a carrier state for 1 year to rest of life 7b. Or bacteria is released into bloodstream (secondary bacteraemia) > Fever, kidney and other organs infected Asymptomatic until bacteria released into bloodstream as secondary bactereamia

Answer 70

can differentiate into an elongated hyperflagellated form > surface motility (‘swarming’) Have swimmer and swarmer cells catheter-associated UTIs (~30% cases) > pyelonephritis produces urease (causes urine pH to increase) > calcium phosphate precipitation > formation of bladder/kidney stones, catheter blockage

Answer 71

environmental opportunistic, nosocomial infections (neonates, elderly, compromised) colonisation of GIT (normal) and oropharynx (less frequent) is benign but can lead to: UTI, pneumonia (aspiration from oropharynx), surgical wound infections, bacteraemia > sepsis (high mortality). multi-drug resistant (resistant to carbapenems)

Answer 72

opportunistic, nosocomial (originating in hospital) outbreaks (including ICUs) infections in lungs, urinary tract, abdominal cavity, intravascular devices, sepsis spread from endogenous gut flora, can survive on skin, patient-to-patient transmission cephalosporin-resistant forms

Answer 73

Y. enterocolitica - localised to ileum: gastroenteritis (diarrhoea with abdominal pain and fever) Y. pestis - systemic: bubonic plague (zoonosis) = ‘black death’

Answer 74

Facultative anaerobe Saline environments: commensal to planktonic crustaceans such as copepods >ingestion by shellfish > contamination of drinking water due to flooding of coastal areas or poor sanitation Curved rods with single polar flagellum

Answer 75

Cholera Characterised by pandemics (7 since 1817) 1P-6P, Indian subcontinent; 7P began in Sulawesi (1961) > SE Asia (1963) > Africa (1970) > Latin America (1991) > Caribbean (2010) O1 serotype > epidemics (and occasionally O139 variant) 1.4-4.0 million cases/yr, 20,000-140,000 associated deaths

Answer 76

Faecal-oral route (not person-to-person) - high infective dose required (faecal contaminated water (poor sanitation) or undercooked shellfish from risk areas) > Incubation, few hours to 5 days (multiplies in small intestine) > Voluminous watery stools (‘secretory’ diarrhoea)

Answer 77

Can lose 20 litres fluid/day plus electrolytes > dehydration/death (hypovolaemic shock) > 50-60% mortality if untreated No blood, pus or fever (i.e. not dysenteric) i.e. no invasion or damage to mucosa# Most cases can be treated with ORT

Answer 78

Cholera toxin (CT) 1.CT binds to a glycolipid receptor on epithelial cell (B subunits) 2. A subunit ADP-ribosylates G-protein (Gs) > locked in ‘ON’ state 3. Uncontrolled cAMP (cyclic AMP) production 4. Protein kinase activated 5. CFTR ion transporter activity modified (loss of Cl- & Na+ into gut lumen) 6. Leads to massive loss of H2O CFTR: cystic fibrosis transmembrane conductance regulator (a Cl- ion transporter)

Answer 79

motile - single polar flagellum ubiquitous, free-living, aerobe opportunistic (serious cause of nosocomial infections) resistant to multiple antibiotics (& disinfectants) - very difficult to treat

Answer 80

Acute infections: Localised: burn/surgical wounds UTI (catheters) keratitis Systemic: (bacteraemic > sepsis) neutropenic patients (leukaemia, chemotherapy, AIDS) ICU patients: (ventilators) leading cause of nosocomial pneumonia Chronic infections: (i) Cystic fibrosis (CF) patients Common denominator to all infections - compromised host defences

Answer 81

Multiple toxins - these are the main virulence determinants in acute infections: Interferes with cell signalling: ExoS (exoenzyme S) ExoU (exoenzyme U) Cell death/ damage: ToxA (exotoxin A) LasB (elastase) PlcH (phospholipase) HCN (cyanide) pyocycanin (generates reactive oxygen species)

Answer 82

Exclusively human parasite: Nasopharyngeal carriage in 25-80% population Opportunistic infections seen mainly in young children and adult smokers: Meningitis* (age <5 yrs), 5-10% of adult cases Bronchopneumonia Epiglottitis*, sinusitis, otitis media Bacteraemia* (often associated with pharyngitis) Pneumonia in CF, COPD, HIV patients

Answer 83

Fastidious - requires ‘factor X’ (haem) and ‘factor Y’ (NAD) therefore, cultured on chocolate agar non - motile

Answer 84

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

Answer 85

Legionnaires’ disease - severe inflammatory pneumonia Immunocompromised Severe Infection from man-made aquatic environments Replicate within freshwater protozoa - intracellular parasite of amoeba Can survive and replicate within alveolar macrophages

Answer 86

pERTUSSIS - Whooping cough B. parapertussis causes mild pharyngitis) Short rods (‘coccobacilli’) Fastidious Humans - only known reservoir Highly contagious (low I.D.) - aerosol transmission Non-specific flu-like symptoms (~7 d), followed by paroxysmal coughing Non-invasive

Answer 87

Pertussis toxin (PT) S1 subunit ADP-ribosylates G-protein (Gi) > locked in ‘OFF’ state (in ON state, Gi inhibits adenylate cyclase) Therefore, PT > cAMP levels rise Adenylate cyclase-haemolysin toxin (CyaA) > cAMP levels rise

Answer 88

PT is composed of 6 protein subunits. Subunit S1 has ADP-ribosylase activity.

Answer 89

suppression of innate immune functions, particularly phagocytosis by macrophages

Answer 90

N. meningitidis N. gonorrhoeae Non-flagellated diplococci Fastidious Two species of medical importance Humans are the only known reservoir Diplococci present in Polymorphonuclear leukocytes of CSF (meningitis) or urethral discharge (gonorrhoea) during infection

Answer 91

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

Answer 92

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

Answer 93

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

Answer 94

Gonorrhoea - second most common STD worldwide Person-to-person only Infection can be asymptomatic (~10% men, ~50% women) Usually characterised by urethritis with additional infection of female genitalia. Serious complications in women - can lead to salpingitis and/or PID if infection ascends.

Answer 95

C. jejuni, C. coli Spiral rods Unipolar (monotrichous) or bipolar (lophotrichous) flagella Most common cause of food poisoning in UK & USA Mild to severe diarrhoea, often with blood - usually self-limiting (< 1 week) Campylobacter shed in faeces for ~3 weeks

Answer 96

Spiral shaped, tuft of polar flagella Present in ~50% global population, but only a fraction develop disease Major role in gastritis and peptic ulcer disease (80-90% of ulcers) Implicated in ~10% cases of gastric adenocarcinoma & mucosa-associated lymphoid tissue lymphoma (linked to production of VacA and CagA toxins)

Answer 97

Non-motile rods Strict anaerobes Commensal flora (large intestine) - most abundant Opportunistic - tissue injury (surgery, perforated appendix or ulcer) > predominantly peritoneal cavity infections (peritonitis, intraabdominal abscesses are most common) can lead to bacteraemia Most frequent cause of anaerobic infections, usually B. fragilis (although it is only 0.5-1.0% of total commensal Bacteroides)

Answer 98

Very small, non-motile. Obligate intracellular parasites. Cannot culture in bacteriological media - detect by serum Abs* or PCR.

Answer 99

1. Elementary bodies (EBs) - rigid, extracellular form, ~0.3 micrometres, dormant infectious enter cell through endocytosis prevent phagosome-lysosome fusion Differentiates into > 2. Reticulate bodies (RBs) - fragile, intracellular form, ~1.0 micrometres, metabolically active replicative non-infectious acquire nutrients from host cell

Answer 100

1. Entry by Elementary bodies 2.Conversion of elementary body to reticulate body 3. Prevention of phagosome-lysosome fusion 4. Multiplication 5. Conversion of reticulate body to elementary body 6. Cell lysis and release of elementary bodies (including DNA condensation)

Answer 101

1. trachoma biovar (serotypes A-C) >trachoma > blindness (eye-to-eye transmission via hands, fomites or flies) 2. genital tract biovar (serotypes D-K) most common STD - infects epithelial cells of mucous membranes of urethra (both sexes) and vagina - can ascend to uterus and ovaries (PID, infertility) - usually asymptomatic (i.e. 70-80% cases in women) -conjunctivitis (STD), hand-to-eye transmission 3. lympho granuloma venereum (LGV) biovar (serotypes L1-L3) -causes LGV (an STD) - invasive urogenital or anorectal infection - endemic to the tropics, cases rising in Europe/N. America

Answer 102

respiratory tract (mild or “walking” pneumonia) - ~10% community acquired pneumonias

Answer 103

Mainly birds psittacosis (zoonotic infection), severe pneumonia

Answer 104

Long, slender, helical, highly flexible Most are free-living and non-pathogenic Pathogenic varieties difficult to culture Modified outer membrane (“outer sheath”) (Treponema and Borrelia lack LPS, replaced by a different glycolipid)

Answer 105

Endoflagella located between peptidoglycan and outer membrane. Fixed at each end of the bacterium and confers shape. Overlap in the centre of the bacterium. Propels bacterium in a corkscrew motion - swim faster in high viscosity medium - hides” antigenic flagellum

Answer 106

Lyme disease (zoonosis) (~300 cases in UK) - bull’s eye rash, flu-like symptoms (fever, fatigue, headache) - dissemination via lymphatics/blood to other organ (neurological problems in 10-15% patients, joints >arthritis)

Answer 107

contact of infected animal urine with mucous membrane or abraded skin - flu-like symptoms - severe form (Weil’s disease*) in 10-15% infected individuals (*jaundice, acute renal and hepatic failure, pulmonary distress, haemorrhage)

Answer 108

Syphilis 1.primary stage - localised genital infection (ulcer (“chancre”)) days-weeks post-infection (highly transmissible phase) 2. secondary stage (~50% cases) - systemic (skin (rash), swollen lymph nodes, joint pains, muscle aches, headache, fever) 1-3 months post-infection (still highly transmissible) 3. tertiary stage (~30% cases) - ‘gummas’ (granulomas) in bone and soft tissue, cardiovascular syphilis (aorta), neurosyphilis (brain and spinal cord). Occurs several years post-infection (non-infectious form)

Answer 109

1. Proteobacteria - all are rod-shaped (bacilli)* except Neisseria (diplococci) and the Campylobacter/Helicobacter genera (spiral) 2. Bacteroidetes (Bacteroides) - rod-shaped (bacilli) 3. Chlamydia - round (elementary bodies), pleiomorphic (reticulate bodies) 4. Spirochaetae (Spirochaetes) - spiral/helical *= some are curved, some are short (coccobacilli), but are bacilli nonetheless

Answer 110

Gut pathogens must be able to survive in low oxygen environments and are therefore usually facultative or obligate anaerobes. For example, Bacteroides are obligate anaerobes, while members of the Enterobacteriaceae and V. cholerae are facultative anaerobes. Campylobacter/Helicobacter genera are microaerophiles. Most of the other pathogenic species discussed are aerobic.

Answer 111

Refers to the name given to a bacterium that has been isolated from a patient to distinguish it from bacteria of the same species that were obtained from other patients. Although the same species, the genome sequences are invariably different among strains due to random mutation/gene loss or acquisition of new genes. However, in an outbreak situation, for example in a hospital ward, you may expect bacteria isolated from different patients to have identical genome sequences

Answer 112

are strains that have antigenic properties that differ from other strains of the same species.

Answer 113

are strains that are distinguished by possession of particular pathogenic mechanisms rather than being based on antigenic differences between molecules on the bacterial cell surface (the serotype). However, different serovars may exist among members of each pathovar

Answer 114

are variant bacterial strains that differ physiologically or biochemically from other strains in a particular species.

Answer 115

Mycobacterium

Answer 116

Leprosy Associated with deformity or loss of fingers Tropical illness Climate is warm Illness of poverty and lack of medical infrastructure Skin lesions causes issue – hypopigmented – can be destructive at the nose Nervous lesions causes problems – damages transition of neural signals – causes loss of sensation – affects distal parts of body like hand and foot – don’t have pain response if you injure there

Answer 117

1,000,000,000

Answer 118

10.4m new cases per year

Answer 119

Gram staining

Answer 120

Ziehl-Neelsen/ Acid fast positive

Answer 121

Slighly curved, beaded bacili High lipid content with mycolic acids in cell wall makes Mycobacteria resistant to Gram stain Ziehl-Neelsen stain Need 10,000 bacili per ml sputum to diagnose

Answer 122

Aerobic, non spore forming, non motile bacillus Cell wall: high molecular,weight lipids +++. Slow growing – M tuberculosis generation time 15-20hr vs 1hr for common bacterial pathogens Significant part of the 4.4 Mb genome of MTB encode genes involved in lipogensis and lipolysis. Key components include: - Mycolic acids - Lipoarabinomannan

Answer 123

Thick lipid rich cell wall making immune cell killing and penetration of drugs challenging Slow growth - Gradual onset of disease – Takes much longer to diagnose – Takes longer to treat

Answer 124

Catch TB from someones lungs when theyre coughing?

Answer 125

-Initial ‘contact’ made by alveolar macrophages in lungs - Bacilli taken in lymphatics to hilar lymph nodes

Answer 126

-Cell mediated immune response (CMI) from T cells - Primary infection contained but CMI persists - Latent TB; . no clinical disease * detectable CMI to TB on tuberculin skin test

Answer 127

- Granulomas forms around bacilli that have settled in apex - In apex of lungs there is more air and less blood suppy (fewer defending white cells to fight) - Could occur immediately following primary infection (post-primary) or after later reactivation - necrosis results in abscess forming and caseous material coughed up

Answer 128

- Granulomas forms around bacilli that have settled in apex - In apex of lungs there is more air and less blood suppy (fewer defending white cells to fight) - Could occur immediately following primary infection (post-primary) or after later reactivation - necrosis results in abscess forming and caseous material coughed up - TB may spread in lung causing other lesions - Granuloma + Lymphatics + Lymph nodes = Primary Complex Causes cough, chest pain, fever

Answer 129

TB meningitis Miliary TB Pleural TB Bone and joint TB Genito urinary TB Bacili in lymph nodes Bacili in lung

Answer 130

* Aerosol transmission * Primary TB in lung * Latent TB can remain for decades * Can spread beyond lungs

Answer 131

1. Mycobacteria are phagocytosed by macrophages and traffic to a phagolysosomes/ phagosome. 2. The bacterium has adapted to the intracellular environment and aims to withstand phagolysosomal killing and escape to the cytosol 3. M. tb eradication can happen by apoptosis mediated cell death, auto phagocytosome, by phagolysosome 4. Effective immunity requires CD4 T-cells which generate interferon gamma and this helps activate intracellular killing by macrophages.

Answer 132

Mycobacteria shut down metabolically in order to survive – dormancy

Answer 133

if it fails, e.g. in the lung, this can result in the formation of a cavity full of live mycobacteria and eventual disseminated disease (consumption)

Answer 134

- Primarily controlled by macrophages - Requires a CD4 T cell response to be controlled - Involves many cells of immunity - formulation of granulomas - Granuloma stability controls reactivation of TB -

Answer 135

* GeneXpert MTB/RIF cartridge based test * Nucleic acid amplification test using PCR * Purifies and concentrates MTB, sonicates to release genomic material and then performs PCR * Rapid result for MTB and detects Rifampicin resistance using fluorescence * Can detect 131 bacilli/ml * Sensitivity 88%, Specificity 98% * Recommended for rapid diagnosis in TB endemic countries

Answer 136

Stimulates T-cell responses in 3-9 weeks after exposure to M. tuberculosis Positive effects: ²+ve effects; macrophage killing of mycobacteria ,containment of infection, formation of tissue granulomata. Negative effects: ; hypersensitivity reactions with skin lesions, eye lesions and swelling of joints This reactivity is measured in the tuberculin skin test where intradermal injection of purified protein derivatives induces skin swelling and redness.

Answer 137

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

Answer 138

injectable agents (streptomycin, cycloserine, capreomycin) * Side effects are wide-ranging and severe, include liver damage

Answer 139

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

Answer 140

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

Answer 141

BPaL regimen : – Bedaquiline – Pretomanid – Linezolid All oral treatments for 6 months These can fail too with totally drug resistant (TTR) TB. No known solution as yet.

Answer 142

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

Answer 143

Lower respiratory infections, diarrheal diseases and HIV/AIDS are leading killers in lower income countries in 2016 40 MILLION with HIV - 8 MIL DONT know their status, 750 undiagnosed

Answer 144

Middle Eastern Respiratory syndrome MERS 2012-now 2578 cases 888 deaths (35%)

Answer 145

Cytomegalovirus (CMV),Varicella Zoster Virus (VZV), Herpes Simplex Virus (HSV), Rubella

Answer 146

. Influenza, Measles, Mumps, Norovirus, Covid

Answer 147

Epstein Barr Virus (EBV) + lymphoma, Hep B/C + hepatocellular carcinoma, Human Papilloma Virus (HPV) + cervical/anal cancer, HIV

Answer 148

An infectious, obligate intracellular parasite comprising genetic material (DNA or RNA) surrounded by a protein coat/ and or membrane All have a receptor binding protein to “dock” to cells All contain genetic material Virus has poisonous fluid Comprises of genrtic materia (DNA or RNA) surround by protein coat and/ or membrane

Answer 149

totally dependant on living cells for their replication and existance

Answer 150

Helical Icosahedral Complex Non-enveloped -adenovirus, parvovirus Enveloped - influenza, HIV

Answer 151

Virions Consist of: Genetic material (DNA or RNA) Protein coat (capsid)

Answer 152

Human viruses range in size from 20 to 260nm in diameter

Answer 153

Cell walls Organelles DNA and RNA

Answer 154

1. Attachment to specific receptors 2. Cell entry - Uncoating of virion within cell 3. HOST CELL INTERACTION + REPLICATION - Migration of genome tocell nucleus - Transcription to mRNA using host materials - Use cell materials (enzymes, amino acids, nucleotides) for their replication; subvert host cell defence mechanisms. - Translation of viral mRNA to produce: - structural proteins, viral genome, non-structural proteins eg enzymes 4. Assembly of virion 5. Release of new virus particles a.Bursts out > cell death eg rhinovirus b. budding/exocytosis e.g. HIV, influenza

Answer 155

A virus is completely dependent on its host cell’s machinery to exist and replicate, and enters a cell with only its genome +/- viral enzymes

Answer 156

1. Direct destruction of host cells 2. Modification of host cells 3. "Over-reactivity" of immune system 4. Damage through cell proliferation 5. Evasion of host defences

Answer 157

host cell lysis and death after a viral replication period of 4 hours e.g poliovirus Polio affects neurons – gets into neurones – destroys neurones – causes weakness and paralysis

Answer 158

E.g. Rotavirus >atrophies villi and flattens epithelial cells >decreases small intestine surface area >nutrients incl sugar not absorbed >hyperosmotic state >profuse diarrhoea

Answer 159

e.g. Hep B Infects liver cells and hepatocytes T lymphocytes comes along and destroys stuff

Answer 160

e.g Human papillovirus (HPV) > Cervical cancer 1. Acquisition through contact 2. Partial viral replication and expression of some HPV proteins 3. Viral DNA integrated into host chromosome 4. Continuous expression of oncoproteins causing cellular DNA mutations 5. Dysplasia and neoplasia > 6. Leads to Cell proliferation and local and metastatic spread

Answer 161

1.HPV (types 16 or 18) infection of suprabasal layer in genital tract. 2.Partial viral replication including transcription and expression of several early viral gene products (E1, E2, E4, E5). 3.Gradual movement of cells to mucosal surface through natural wear and tear. 4.At some point during this process the HPV genome may become integrated into the host cell chromosome. Mutagenic agents (eg nicotine) may increase the chance of integration. 5.Following integration, control of viral gene expression by the HPV E2 protein is lost and the HPV E6 and E7 proteins may be expressed. 6.Two cell growth and proliferation suppressor proteins, Rb (retinoblastoma) and p53 are prevented from operating. 7.Excessive cell growth and proliferation occurs and cervical cell carcinoma results.

Answer 162

After primary disease, virus not detectable but viral DNA lies latent and can reactivate, particularly at times of lower immune control (illness/immunosuppression/advancing age) Can hide in nerve root ganglion, Lymphoid cells, Myeloid cells Lymphoid cells - T cells, B cells, NK cells Myeloid cells - monocytes, macrophages, neutrophils, basophils, eosinophils etc

Answer 163

Primary - chickenpox Reactivation - when immune system suppressed - Shingles

Answer 164

E.g. Measles and HIV Direct cell to cell spread has multiple advantages Avoids random release into the environment Increased speed of spread within tissues Avoiding immune system

Answer 165

Antigenic variability eg influenza, HIV, rhinovirus Ability to change the surface antigens in order to evade the host’s immune system Explains: - how a host can be re-infected with the same virus e.g. common cold - why with influenza vaccination is required annually, as each season a different viral strain is circulating

Answer 166

In response to a viral infection, many cells undergo apoptosis, which reduces the amount of virus released from the cell Prevention of host cell apoptosis allows the virus to continue replicating within it, so more virus is produced and then released. It also has an essential role into how some viruses are oncogenic (cancer causing). Flu can recombine itself in different configurations

Answer 167

In normal cells: Interferon synthesis stimulated > Antiviral state activated in neighbouring cells In affected cells: Interferon synthesis blocked > Neighbouring cell susceptible to infection

Answer 168

> Different host cells and tissues that they can infect > Different methods of interaction with the host cell

Answer 169

IgG IgM IgE IgD IgA

Answer 170

Cell-mediated immunity Antibody-mediated immunity Vaccination stimulates immune response and memory to a specific antigen/infection

Answer 171

Breastmilk

Answer 172

Protection provided from the transfer of antibodies from immune individuals. Most commonly 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) Protection is temporary – usually only a few weeks or months. #Immunity from someone else or a different source First couple of months baby immunised using mothers breast milk antibodies Antibodies degrade overtime Active immunity is different Active immunity gives you longer lasting immunity

Answer 173

inactivated (killed) (e.g. pertussis, inactivated polio) attenuated live organisms (e.g. yellow fever, MMR, polio, BCG) secreted products (e.g. tetanus, diphtheria toxoids) the constituents of cell walls/subunits (e.g. Hep B) or recombinant components (experimental)

Answer 174

Get population immunity through vaccination or past infection

Answer 175

No vaccine offers 100% protection Small proportion of individuals get infected despite vaccination. Primary vaccine failure – person doesn’t develop immunity from vaccine. Secondary vaccine failure – initially responds but protection wanes over time. No such thing as perfect vaccine Some people don’t have enough immune response Vaccine expired, don’t get administered the proper way

Answer 176

Diptheria Tetany/ Tetanus Pertussis/ Whooping cough Polio Haemophilus influenzae type B Meningococcal disease

Answer 177

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 or spending in excess of eight hours in the same room

Answer 178

Anthrax Cholera Plague Rabies SARS Smallpox Viral haemorrhagic fever Yellow fever

Answer 179

Acute encephalitis Botulism Brucellosis Enteric fever (Typhoid & Paratyphoid fever) Haemolytic Uraemic Syndrome

Answer 180

Acute poliomyelitis Diphtheria Measles Mumps Rubella Tetanus Whooping cough Acute Meningitis / Meningococcal septicaemia

Answer 181

Acute infectious hepatitis Foodborne Food poisoning Botulism Enteric fevers Infectious bloody diarrhoea Scarlet fever Tuberculosis

Answer 182

Detection of any changes in a disease >Outbreak detection >Early warning >Forecasting Track changes in disease >Extent and severity of disease >Risk factors Allows development of interventions targeted at vulnerable groups

Answer 183

Investigate: contact tracing, partner notification, lookback exercises, etc… Identify and protect vulnerable persons: e.g. chemoprophylaxis, immunisation, isolation Exclude high risk persons or from high risk settings Educate, inform, raise awareness, health promotion Coordinate multi-agency responses

Answer 184

Source > Pathway > Receptor

Answer 185

“One celled animals” Single cell with nucleus (Eukarytoic) >30,000 species Show characteristics usually associated with animals Eg mobility

Answer 186

Flaggelates Amoebae Sporozoan Cilliates Microsporidia

Answer 187

Trypanosoma spp Leishmania spp Trichomonas vaginalis Giardia lamblia

Answer 188

Tsetse fly bite Chancre Flu like symptoms CNS involvement -(sleepy, confusion, personality change) Coma and death Diagnosed on blood film or CSF

Answer 189

Spread by Triatomine Bug Acute:Flu like symptoms Chronic: Cardiomyopathy Megaoesophagus Megacolon Spread through contact with faeces of triatomine “kissing” bug Also through blood, vertically and eating contaminated food Millions have undiagnosed Chagas in the Americas Two phases, both can be asymptomatic or life threatening

Answer 190

Spread by the bite of the sandfly >20 species affect humans Three clinical pictures: Cutaneous Mucocutaneous Visceral

Answer 191

Sexually transmitted Asymptomatic Dysuria Yellow frothy discharge Treated with Metronidazole Seen on wet prep of high vaginal swab STI – endemic to UK Take swab of vagina and put it on a plate with water

Answer 192

Faeco-oral spread Diarrhoea Cramps, bloating, flatulence Recent travel, childcare Trophozoites/cysts seen in stool Treated with metronidazole

Answer 193

Faeco-oral spread Dysentry, Colitis,Liver and lung abscesses Trophozoites/cysts seen in stool Treated with metronidazole Poor sanitary conditions/tropical countries MSM (men who have sex with men) at risk

Answer 194

Entamoeba histolytica

Answer 195

Entamoeba histolytica

Answer 196

Waterborne Diarrhoea (Watery, no blood) Vomiting, fever, weight loss Oocytes seen in stool (acid fast!) Usually self limiting Severe disease in immunocompromised Poor sanitary conditions/tropical countries MSM Children Swimmers Contaminated recreational water sources

Answer 197

Ingestion of contaminated foodand water/feline faeces Can cause: - Disseminated disease - Toxoplasma Encephalitis - Chorioretinitis Acute maternal infection can be devastating in pregnancy Up to half of the UK population will have the infection at some point. Occurs worldwide (Except Antarctica). Acquired through the ingestion of oocytes by contact with cat faeces (having kittens at home, contaminated soil or water), or ingestion of bradyzoites (tissue cysts) in contaminated food (eg rare beef/lamb, shellfish, unpasteurised goats milk) Cats are the only definitive hosts (full cycle occurs, ingestion to excretion)

Answer 198

Travel with Malaria

Answer 199

female anopheles mosquito

Answer 200

Plasmodium falciparum Plasmodium ovale Plasmodium vivax Plasmodium malariae Plasmodium knowlesi

Answer 201

Falciparium tends to cause the most severe disease and mortality untreated is very high Early identification and treatment is key to prevent death Presentation tends to occur within a month for falcip Vivax and ovale can be up to a year! Falciparum most prevalent and can kill Rest don’t cause death but can cause illness

Answer 202

Light microscopy A blood sample is taken for “thick and thin” films The thick film is sensitive but low resolution> does this person have malaria? Yes or no The thin film helps identify the species as each looks different, and also is used to work out the parasitaemia percentage > what species of malaria does this person have

Answer 203

FEVER Chills Headache Myalgia Fatigue Diarrhoea Vomiting Abdo pain

Answer 204

Anaemia Jaundice Hepatosplenomegaly - big spleen and liver ‘Black Water Fever’ - occurs from haemolysis

Answer 205

1. Within the mosquito the gametocytes are within the midgut, and undergo development, end up as sporozoites in the salivary glands of the mosquito 2. Mosquito takes its next blood meal and injects the sporozoites into the human 3. Sporozoites injected into blood infect the hepatocytes in the liver (Abdominal pain) 4. Develops into a schizont, which then bursts and infects red blood cells (Abdominal pain) 5. Within the red blood cell, plasmodium becomes a trophozoite -This is one of the forms we can see on a blood film to diagnose malaria 6. The trophozoite develops into a schizont, which then ruptures and re-infects another RBC This blood stage lasts 48 hours in most of the plasmodium species: >Cyclical fever when RBCs rupture >Haemolysis >Anaemia >Jaundice from bilirubinaemia 7. Some of the trophozoites develop into gametocytes 8. Whhich are then taken up by another mosquito

Answer 206

OBSTRUCTED MICROCIRCULATION which can lead to “COMPLICATED MALARIA” The pathophysiology of complicated malaria is mostly down to the infected RBCs ability to adhere to endothelial cells

Answer 207

They have proteinaceous knobs on the surface that bind to endothelial cells in the vessels and other RBCs This can cause small vessels to become obstructed by clumps of red blood cells causing hypoxia of the tissues, microinfarcts in brain and lung

Answer 208

Vascular occlusion> Drowsy, Increased Intercranial pressure, seizures, coma Hypoglycaemia > drowsiness

Answer 209

Anaemia and lactic acidosis can cause a fast respiratory rate (tachypnoea) through compensatory mechanisms. Increased vascular permeability causes fluid to leak directly into the lungs causing pulmonary oedema.

Answer 210

Shortness of breath due to > due to anaemia due to lactic acidosis (compensatory) due to increased vascular permeability  pulmonary oedema

Answer 211

A direct effect through vascular occlusion Hypoperfusion secondary to dehydration (fever) or hypotension Haemolysis creating products that can be nephrotoxic Vascular occlusion Dehydration Hypotension Haemoglobulinuria Haemolysis These cause: Proteinuria Fatigue Haematuria

Answer 212

Thrombocytopenia occurs through platelet aggregation and therefore reduced circulating platelets Generalised inflammation activates the coagulation cascade, causing clotting factors to be used up. This then causes DIC (disseminated intravascular coagulation) – lots of micro clots have formed in the blood, but a lack of circulating clotting factors causes bleeding This causes: Epistaxis Abnormal bleeding Worsening anaemia

Answer 213

The heart and circulatory system are affected in lots of ways. The patient can develop shock due to: Hypovolaemia: bleeding or vasodilation (inflammatory cascade and sepsis) Anaemia > inadequate oxygenation to heart

Answer 214

-Pro-inflammatory cascade causing vasodilation -Anaemia (if bad enough) can cause cardiogenic shock -Gram negative sepsis can occur from increased vascular permeability in the bowel > so gram negative bacteria colonising the bowel can enter the bloodstream -Bleeding causes a hypovolaemic shock -Increased vascular permeability means that intravascular fluid can leak out into the “third space”

Answer 215

Adherence to endothelial cells by the parasitised RBC causes a local expression of cell-adhesion molecules causing red blood cells and platelets to bind causing thrombocytopenia through platelets use, and occlusion of small vessels.

Answer 216

There is a proinflammatory cytokine cascade which: alters the endothelial cell wall function > Leaky vessels > ARDS, gram –ve sepsis, shock Switches cells to anaerobic metabolism > hypoxia and lactate increases Reduces gluconeogenesis > hypoglycaemia

Answer 217

Cerebral ARDS/Pulmonary oedema Renal failure Sepsis Bleeding/Anaemia

Answer 218

Complicated - IV artesunate - (IV quinine + doxycycline) Uncomplicated - Lots of options!

Answer 219

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

Answer 220

Vivax and ovale species can develop hypnozoites in the liver which can “reactivate”. Ie once a patient recovers from the first episode of malaria, they can suffer relapses of malaria months or years later. These can lie dormant for years!! They aren’t treated by the treatment for acute malaria Require primiquine to kill the hypnozoites and therefore stop a relapse occurring Primiquine can cause haemolysis if deficient in G6PD

Answer 221

One virus – two diseases Varicella “chickenpox” – PRIMARY INFECTION Herpes Zoster (HZ) “Shingles” – SECONDARY REACTIVATION Glycoprotein spikes Lipid envelope Double-stranded DNA genome Nucleocapsid Tegument

Answer 222

When you know you dont have the virus

Answer 223

Risk of transmission is highest to other is 48 hours before you get the spot and first couple of day after the spots emerge

Answer 224

Chickenpox replicates in nasopharynx and is in nasal secretions – breathe cough and sneeze so you pass on to others If someone touches vesicles (spots) get it on your own skin

Answer 225

Common in childhood Highly contagious, Usually benign but can be serious in certain groups e.g. -Immunocompromised and patients who have had transplants -Adults -Pregnant women -Smokers -Infants -90% of adults raised in the UK have had chickenpox

Answer 226

Macule to papule to vesicle to pustule to crust Initially just a blob Rash evolves to papule – run your finger over lesion you feel it Papule becomes blister filled with blister fluid which is infectious WBC response – rush to vesicle carrying immune response with them and become pustule – pus filled Then become crust Chicken pox likes to divide in warm areas – spares cooler areas

Answer 227

Smallpox lesions all evolve at the same time whereas with chickenpox and measles, lesions at different stages of progression can appear on the body concurrently

Answer 228

Consider: Age of the patient Onset of rash Any contacts? Immuno-suppressed? Pregnant?

Answer 229

-Pop lesion with a sterile needle (Don’t wipe it with alcohol swab first) -Absorb vesicle contents onto swab -Replace swab in cassette and send for VZV/HSV PCR

Answer 230

-Dehydration -Haemorrhagic change -Cerebellar ataxia (common) – unsteady gait – common in children -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 Seizures Confusion Lose motor function More in adults then children

Answer 231

Chickenpox pneumonitis affects 15% of healthy adults Risk doubles if underlying lung disease or if a smoker 30% mortality untreated Mortality 6% even with adequate treatment

Answer 232

Chest x-ray should be black - patchy white shadowing is bad

Answer 233

Foetal infection occurs in 10-15% of cases of chickenpox in pregnancy -Usually transient and asymptomatic -If any manifestations – shingles in the first year of life -If maternal chickenpox occurs in the first half of pregnancy, about 2% of infants will develop FVS

Answer 234

Cicatricial skin scarring Limb hypoplasia –poorly developed limb Visceral and ocular lesions Microcephaly and growth retardation Right leg lost musculature of calf, no toes, not well defined ankles

Answer 235

Blood sample Tube contains gel to separate cells from serum once centrifuged Small sarsted tubes kept for about 3 years Take clotted sample from all pregnant women when they book first appointment Centrifuge sample – serum separation gel risen up and formed barrier between clot at bottom and serum at top – stored for 3 or 4 years

Answer 236

IGM molecule – 5 pronged molecule – 10 binding site – first mode of defence from our b cells IGM response can be non specific – don’t use igm very often to diagnose virus

Answer 237

memory antibody – tight bond between antigen and antibody – nearly unbreakable – prodcues memory immune response and defence against that pathogen when its seen again – opposite to igm

Answer 238

Primary infection - widespread chickenpox > Viral dormancy in dorsal root or cerebral ganglion > Localised reactivation – shingles DNA viruses might have dormant phase Hepatitis B – good eg – sits in liver cells –evades a lot of immune responses – hard to get rid of once established Herpes similar – Single sensory nerve supplies single patch of skin – because its on either side – shingles rash wont migrate across the midline – stays unilateral

Answer 239

Most common in the elderly 250,000 people estimated to be affected annually in England and Wales Around 1/1000 people over seventy who have shingles will die of the infection

Answer 240

Thoracic region most commonly involved (50-70% of all cases) Cervical, lumbar and sacral dermatomes are less frequently involved 10-20% of cases are ophthalmic -Affecting the ophthalmic division of the trigeminal nerve Ocular shingles affects the eye Shingles is painful Have to use drugs that dampen down the abnormal nerve responses in nerve endings

Answer 241

Lesion at the end of the nose – nasociliary branch of the ophthalmic division of the trigeminal nerve supplies skin to tip of nose – sign that you have corneal involvement – could affect eye

Answer 242

lose fluid into those lesions – lose a loot of blood volume into lesions of the skin – could be life threatening – eczema hepatica

Answer 243

Infections: Parvovirus B19 Rubella Hepatitis B Neisseria gonorrhoeae Neisseria meningitidis Streptococci Spirochaetes Borrelia burgdorferi

Answer 244

Hand foot and mouth disease? Secondary syphillus can do this Diagnose this just the same way Enteroviruses get shed in their stool Can cause viral meningitis or myocarditis

Answer 245

Not the same thing that affects dog Targets immature red cells – red cells in marrow has nucleus present display on surface p antigen – parvovirus attaches to those and it prevents normal red cell maturation – red cells die but cant be replaced from marrow Worry about kids and pregnant women

Answer 246

Marrow with nuclear material around red cell – shows how the red cell formation occurs and how immature red cells an be targeted by that virus

Answer 247

Can happen through an intrauterine fusion (from IV bag) which can cause a fetus to receive a blood transfusion through the umbilical vein in the placenta

Answer 248

Looks reticular in body Tree like

Answer 249

HSV1 can be both mouth and down below HSV 2 is just down below

Answer 250

Shedding of epithelium from inside of mouth – that becomes moist area where bugs can target and get into the body

Answer 251

Infection causes glandular fever type initially Teens and twenty year olds Most people have had it once theyre 60 Lymphocytes become a bit destructive and red cells stick to them

Answer 252

In immunosuppressed patients its common to reactivate HIV patients retinitis is a problem Bottom left retina has lots of CMV - pizza pan retina because it looks like cheese Top right histological hallmark of CMV – lots of nucleus

Answer 253

Transmissible R nought for measles is 16 Real profound rash – becomes dry and desquamating Measles makes kid miserable

Answer 254

Agents produced by micro-organisms that kill or inhibit the growth of other micro-organisms in high -dilution Not necessarily an anti bacterial Most agents currently used are semi-synthetic derivatives of antibiotics so more correctly termed ‘antimicrobials’. Antimicrobials include antifungal, antibacterial, antihelminthic, antiprotozoal and antiviral agents BUT, in practice antibiotic = antibacterial Penicillin discovered by Alexander Fleming in 1929 was the the first antibiotic. Better term that kill infectious pathogens is antimicrobials Some agents are antibacterial and antiprotozoal and antifungal – theyre all 3

Answer 255

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 antibiotic class

Answer 256

Where antibiotic binds – defines class of antibiotic it belongs too Main binding site is bacterial cell wall

Answer 257

Beta Lactams -Penicillins -Cephalosporins -Carbapenems -Monobactams Beta lactam ring which is a key part of the molecule which is common to all beta lactam antibiotics – helps antibiotic bind to penicillin binding protein Vancomyocin Bacitracin Cell membrane - Polymyins

Answer 258

Folate synthesis - Important in production in building blocks to make nucleic acids - Sulfonamides - Trimethoprim Sulphamethoxazole Trimethoprim Co-trimoxazole DNA gyrase - Quinolones -Metronidazole -Fluoroquinolones RNA polymerase - Rifampin Ciprofloxacin Levofloxacin Moxifloxacin

Answer 259

50s subunit (ribosome) - macrolides - Clindamyacin - Linezolid - Chloramphenicol - Streptogramins 30s subunit - Tetracyclines - Doxycycline - Aminoglycosides - Gentamiacin Lincosamides - Clindamyacin Macrolides Erythromycin Clarithromycin Azithromycin Chloramphenicol

Answer 260

Gram positive Beta lactam and glycopeptides are particulary useful for gram positive bacteria – do have a role in gram negative bacteria

Answer 261

To bind to the PBPs, the β-lactam antibiotic must first diffuse through the bacterial cell wall. Key thing in cell wall matrix is peptidoglycan – peptides and sugars Key binding sites that allow peptidoglycan to work as cement within bricks – that cement where antibiotics work and disrupt When penicillin binding proteins are disrupted by antibiotics such as penicillin lose integrity of cell wall and get lysis Bacteria explodes and dies disrupt peptidoglycan production by binding covalently and irreversibly to the Penicillin Binding Proteins cell wall is disrupted and lysis occurs results in a hypo-osmotic or iso-osmotic environment Active only against rapidly multiplying organisms

Answer 262

Gram-negative organisms have an additional lipopolysaccharide layer that decreases antibiotic penetration. Makes it harder for beta lactams. Differences in the spectrum and activity of β-lactam antibiotics are due to their relative affinity for different PBPs. Need chemically engineered beta lactam for gram negative

Answer 263

Because the penicillins poorly penetrate mammalian cells, they are ineffective in the treatment of intracellular pathogens.

Answer 264

DNA/RNA synthesis, protein synthesis -Similar to mammalian -Flucytosine Cell Wall -mannoproteins -Β1,3 glucan -Β1,6 glucan -chitin -Doesn’t exist in humans -Echinocandins Plasma membrane -ergosterol -Human cell membrane contains cholesterol not ergosterol -Amphotericin -Azoles -Terbinafine

Answer 265

Antibiotics have been around for <100 years, yet human race survived! Antibiotics give time and support for the immune system to deal with an infection.

Answer 266

Attach and enter > Local Spread > Multiply > Evade host defences > Shed from body Consequences: destroy phagocytes or cells in which bacteria replicate Exotoxin - Protein production Endotoxin - Gram negative Inflammation – e.g. necrotic cells Immune-pathology – e.g. antibody Diarrhoea

Answer 267

The agent kills the bacteria Kill >99.9% in 18-24 hrs Antibiotics that inhibit cell wall synthesis Useful if poor penetration (Endocarditis), difficult to treat infections or need to eradicate infection quickly (meningitis

Answer 268

Sepsis – the infection has become severe despite a functioning immune system and is so aggressive that the patient will die before a static antibiotic is able to help

Answer 269

The infection will cause death or irreversible brain damage before a static antibiotic will help

Answer 270

The infection is in a site where the patient’s own immune system is unable to deal with the bacteria and therefore a static antibiotic won’t eliminate the bacteria as it is working alone (Bacteria within cardiac vegetations are at high concentration, and have lower rates of metabolism and cell division or are dormant, being surrounded by fibrin, platelets, and possibly calcified material. High levels of bactericidal agents are required for a prolonged period)

Answer 271

the patient doesn’t have a properly functioning immune system to work with a static antibiotic e.g. febrile neutropaenia They either kill the bacteria pretty quickly – usually the cell wall ones – really useful in certain conditions or if it’s a quite hard to treat infection where you need everything you can

Answer 272

prevent growth of bacteria ‘inhibitory to growth’ In fact kill >90% in 18-24 hrs defined as a ratio of Minimum Bactericidal Concentration (MBC) to Minimum inhibitory Concentration (MIC) of > 4 Antibiotics that Inhibit protein synthesis, DNA replication or metabolism Reduce toxin production and Endotoxin surge less likely Do actually kill most bacteria Single bacterium doesn’t last too long anyway Exotoxin or endotoxins less likely to cause damage No one antibiotic is only one of those 2 groups – different antibioitcs work in different ways at different times

Answer 273

Can lead to release of endotoxin (essentially bits of the cell wall) and the resulting increase in antigenic load causes an aggressive and dangerous inflammatory response

Answer 274

Minimum inhibitory concentration: testing to see if pathogen is resistant to antibiotics

Answer 275

Step 1: Tube dilation Step 2: Incubate for 24 hours Step 3: Determine MIC based on turbidity What we do is have tubes with broth that promotes growth of bacteria (culture medium but its liquid) – mix that broth with different concentrations of antibiotic your testing – from 0 mls to pure antibiotic – if broth is pure antibiotic and no media imagine the bacteria unlikely to go – vice versa bacteria should grow – can work out at what point conc of antibiotic is enough to inihibit the bacterial growth

Answer 276

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 antibiotic 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. The two major determinants of anti bacterial effects are the concentration and the time that the antibiotic remains on these binding sites

Answer 277

Key parameter is the time that serum concentrations remain above the MIC during the dosing interval: t>MIC beta-lactams (penicillins, cephalosporins, carbapenems, monobactams), clindamycin, macrolides oxazolidinones

Answer 278

Key parameter is how high the concentration is above MIC peak concentration/MIC ratio aminoglycosides quinolones

Answer 279

The movement of a drug from its administration site to the place of its pharmacologic activity and then its elimination from the body A function of: 1.Its release from the dosage form; 2.Its absorption from the site of administration into the bloodstream; 3.Its distribution to various parts of the body, including the site of action and 4.Its rate of elimination from the body via metabolism (LIVER) or excretion (KIDNEY) of unchanged drug.

Answer 280

Oral IV Suppository - for mucosal absorption

Answer 281

Which antibiotics will penetrate that site? What is the pH of the site? Is the antibiotic lipid soluble? Lipid soluble pH affects your distribution How much fat someones got in their body Not just your physiological status If you have collection of pus don’t have system of blood vessels going into middle of that – take antibioitcs to ege and hope it finds its way to the middle Heart valves don’t have blood supply – get antibioitcs to heart valve have to flow Size of molecule could be really important F – small molecule – first thing for SA - Staph aureus Alternative to F is Vancomyocin – when it has resistance

Answer 282

Change antibiotic target Destroy antibiotic Prevent antibiotic access Remove antibiotic from bacteria Beta lactamases

Answer 283

Target protein is what antibiotic binds to in pathogen – target protein aa sequence determined by the genetic sequence of nucleoside bases in DNA – if this gets changed get diff AA sequence so diff peptide means the protein shape folded is slightly different and antibiotic molecule cant bind to it anymore Another gene might get switched on that produces a molecule that binds that site and blocks it from the anti microbial but it doesn’t itself affect the function of the molecule it binds to – changing the antibiotic target

Answer 284

Flucloxacillin (or methicillin) is no longer able to bind PBP of Staphylococci – Methicillin resistant S. aureus Wall components change in enterococci and reduce vancomycin binding – Vancomycin resistant Enterococci Rifampicin activity reduced by changes to RNA polymerase in MTB – MDR-TB$

Answer 285

The antibiotic is destroyed or inactivated e.g. 1.Beta lactam ring of Penicillins and cephalosproins hydrolysed by bacterial enzyme ‘Beta lactamase’ now unable to bind PBP 2. Staphylococci produce ‘penicillinase’ so penicillin but not flucloxacillin inactivated 3. Gram negative bacteria phosphorylate and acetylate aminoglycosides (gentamicin)

Answer 286

-modify the bacterial membrane porin channel size, numbers and selectivity e.g. 1.Pseudomonas aeruginosa against imipenem, 2.Gram negative bacteria against aminoglycosides

Answer 287

-Proteins in bacterial membranes act as an export or efflux pumps - so level of antibiotic is reduced -S. aureus or S. pneumoniae resistance to fluoroquinolones -Enterobacteriacae resistance to tetracylines -Bacteria produces new channel/ pump that pumps out the molecule/ antibiotic

Answer 288

Intrinsic > Naturally resistant Acquired> Spontaneous gene mutation or Horizontal gene transfer Horizontal gene transfer > Conjugation, transduction, transformation

Answer 289

-All subpopulations of a species will be equally resistant examples: -Aerobic bacteria are unable to reduce metronidazole to its active form -Anaerobic bacteria lack oxidative metabolism required to uptake aminoglycosides -Vancomycin cannot penetrate outer membrane of gram negative bacteria – just too big a molecule to get in -The PBP in enterococci are not effectively bound by the cephalosporins

Answer 290

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

Answer 291

New nucleotide base pair change in amino acid sequence change to enzyme or cell structure reduced affinity or activity of antibiotic These all lead to > MTB - Point mutations in the rifampin-binding region of rpoB

Answer 292

MRSA - acquisition of mecA genes which is on a mobile genetic element called “staphylococcal cassette chromosome”

Answer 293

Pre designed method for bacteria to share DNA through plasmid transfer Mechanism of gene transfer responsible for most concerning aspects of antimicrobrial resistance. Sex pilus (small tube) forms between 2 bacterial cells through which plasmid is transferred from one to another.

Answer 294

viruses that attack bacteria are moving genetic material from one bacterium to the next by accident – tryna move viral genetic material – main mechanism for mrsa to develop Bacteriophages (viruses that infect bacteria) mediate transfer of DNA between bacteria via transduction - where DNA from donor bacterium is packaged into a virus particle and transferred into a recipient bacterium during infection

Answer 295

Transformation where bacterial dna can get swallowed up by bacteria and get integrated into its genome Some bacteria are able to take up free DNA from the environment and incorporate it into their chrosome

Answer 296

New Delhi metallo-β-lactamase, ESβLs

Answer 297

mecA genes for MRSA

Answer 298

foreign DNA from S. mitis to S. pneumoniae, conferring penicillin resistance

Answer 299

Gram-positive bacteria Methicillin resistant Staphylococcus aureus Bacteriophage mediated acquisition of Staphylococcal cassette chromosome mec (SCCmec) contains resistance gene mecA encodes penicillin-binding protein 2a (PBP2a) confers resistance to all β-lactam antibiotics in addition to methicillin (= flucloxacillin)

Answer 300

Gram positive bacteria vancomycin-resistant enterococci Plasmid mediated acquisition of gene encoding altered amino acid on peptide chain preventing vancomycin binding Promoted by cephalosporin use

Answer 301

Gram-negative bacteria -Extended spectrum beta lactamase (ESBL) inhibition -These hydrolise oxyimino side chains of cephalosporins: cefotaxime, ceftriaxone, and ceftazidime and monobactams: aztreonam -TEM-1 in E. coli, H. influenzae and N. gonorrhoea -SHV-1 in K. pneumoniae -An even more extensive ESBL, this time plasmid mediated, is the CTX-M cephalosporinase in Enterobacteriacae

Answer 302

beta-lactamase inhibitors

Answer 303

Co-Amoxiclav

Answer 304

-Broad spectrum penicillin, cephalosporin and monobactam resistance -encoded on the chromosome in bacteria such as Citrobacter spp., Serratia marcescens, Enterobacter spp. -b-lactamase inhibitor resistant! -inducible expression (gene only turned on by antibiotic)

Answer 305

Carbapenems such as ertapenem, imipenem, meropenem -in contrast to other b-lactams, are highly resistant to degradation by b-lactamases or cephalosporinases. -often the antimicrobials of last resort to treat infections due to ESBL or AmpC -producing organisms of the Enterobacteriacae family*.

Answer 306

carbapenemases Treatment options are very few and very toxic

Answer 307

can cause severe skin infections – can be necrotizing

Answer 308

Intolerance, allergy and anaphylaxis Side effects Age Renal and Liver function Pregnancy and breast feeding Drug interactions Risk of Clostridium difficile

Answer 309

Theyre cell wall (peptidoglycan) weapons act on cell wall of bacteria – inhibit cell wall synthesis – bacterial cell undergoes lysis – bacteria dies

Answer 310

Peptidoglycan

Answer 311

gram negative have thinner layer of peptidoglycan than gram positive

Answer 312

Penicillin V Benzylpenicillin Flucloxacillin Amoxicillin

Answer 313

Side chains of beta-lactams will impart different spectrum of activity

Answer 314

Cephalexin Cefuroxime Ceftriaxone Cefotaxime

Answer 315

Good for people with penicillin allergy Work against some resistant bacteria Get into different parts of the body e.g. meningitis

Answer 316

Own special group in beta lactams – for people with non severe penicillin allergy – can be broader – come in different types and generations

Answer 317

Gram stain > Gram > Catalase test > If positive We have staphylococcus if negative we hve streptococcus Coagulase on staphylococcus > if positive S. aureus

Answer 318

Gram stain > Gram + coccus > streptococcus > haemolysis on blood agar: If beta we have Lancefield group strep GROUP A C G strep If alpha > optochin > sensitive = Streptococcus pneumoniae

Answer 319

THICK CELL WALL THEREFORE NEED A SIMPLE CELL WALL WEAPOn think beta-lactams

Answer 320

FLUCLOXACILLIN

Answer 321

PO PENICILLIN V IV BENZYLPENCILLIN NO PENICILLIN RESISTANCE*

Answer 322

PO AMOXICILLIN IV BENZYLPENCILLIN

Answer 323

Methicillin*-resistant Staphylococcus aureus

Answer 324

Activity: Gram positive ONLY Use: Gram positive bacteria resistant to beta-lactams e.g. MRSA, enterococci, some coag neg staph Use: penicillin allergy Only given IV Need to know its level in patients blood Nephrotoxic – bad for kidneys

Answer 325

Inhibitors of cell wall synthesis Inhibitors of protein synthesis Inhibitors of nucleic acid synthesis Anti-metabolites Inhibitors of membrane function

Answer 326

Clarithromycin and erythromycin – oral (& IV) Activity: Gram positives (S. aureus, β haemolytic strep) and atypical pneumonia pathogens Use: penicillin allergy Use: severe pneumonia

Answer 327

legionella – multiply inside cells, no good having a cell wall active antibiotic as can’t get to it if it’s hiding inside a cell

Answer 328

Activity: Gram positives eg S. aureus, β haemolytic strep , anaerobes Use: cellulitis (if pen allergy) Use: necrotising fasciitis (remember Elizabeth…) TURNS OFF NASTY TOXINS MADE BY Gram positive bugs*

Answer 329

Doxycycline = oral Activity : Broad spectrum but mainly Gram positive (S. aureus and streps) Use: cellulitis (if penicillin allergy) Use: pneumonia

Answer 330

Gram stain > Gram (rods) > Lactose fermentation > if positive Enterobacteriacae (coliforms) like Escherichia coli, Klebsiella > if negative Shigella, salmonella, proteus Pseudomonas (oxidase positive)

Answer 331

IV only Activity : Gram negatives and staphs (use synergistically to treat streps) Use: urinary tract infections (UTIs) Use: infective endocarditis (synergistically) Nephrotic Use synergistically to treat some gram-positive bacteria

Answer 332

Ciprofloxacin = oral (& IV) Activity : Gram negative>> Gram positive Use: penicillin allergy Use: UTIs Use: intra-abdominal infections Inhibit DNA synthesis

Answer 333

anti-metabolite (folate antagonist) Activity: Broad spectrum but mainly used for Gram negatives Use: UTIs

Answer 334

Activity: Gram negatives and gram positives Use: Lower UTIs

Answer 335

Beta lactamases

Answer 336

oral and IV Activity: S. aureus, streps, enterococci, gram negatives, anaerobes Use: aspiration pneumonia, severe CAP, more resistant urinary organisms

Answer 337

Activity: Few gaps. No cover for ESBLs/AmpCs Use: HA-pneumonia, systemic Pseudomonas infections, >65s abdominal infection, immunocompromised Broad spectrum Doesn’t cover more resistant ESBLs

Answer 338

Activity: gram positives and gram negatives. No cover for Pseudomonas, anaerobes and enterococci Use: some surgical prophylaxis, <65s intra-abdominal infections, non-severe penicillin allergy Good cover for gram positive and gram negative

Answer 339

Activity: BROAD. Active against ESBLs/AmpCs. Use: HAI (sickest, most at risk), resistant gram negatives, immunocompromised Need special code to use – restricted use Broadest spectrum antibiotic – use against very resistant bacteria

Answer 340

Since AB developed saved countless lives – at point now every new antibiotic has resistance – not enough new weapons to counteract this – new resistance every couple of years

Answer 341

Likely diagnosis Urinary tract infection (lower) Bacteria: gram negatives (E. coli, proteus, klebsiella) And gram positives (staph saprophyticus) Samples Consider urine culture if possibility Resistance ✓ Children, pregnancy, men, > 65s, sepsis/pyelonephritis, catheter

Answer 342

Cellulitis usually lower limbs - unilateral Red, hot, painful, tender skin Spreading Systemic symptoms Bacteria: S. aureus and β haemolytic strep (Group A, C & G)

Answer 343

Eukaryotic Chitinous cell wall Heterotrophic “Move” by means of growth or through the generation of spores (conidia), which are carried through air or water Move passively Produce spores that can move through water

Answer 344

Yeasts are small single celled organisms that divide by budding -Account for <1% of fungal species but include several highly medically relevant ones

Answer 345

Moulds form multicellular hyphae and spores Some fungi exist as both yeasts and moulds switching between the two when conditions suit – dimorphic fungi

Answer 346

Superficial

Answer 347

Invasive - can be easily missed

Answer 348

Nappy rash and Vulvovaginal candidiasis Tinea pedis (athlete’s foot) Onychomycosis (fungal nail infections) Otitis externa

Answer 349

Candida line infections Invasive aspergillosis Pneumocystis Cryptococcosis Mucormycosis

Answer 350

Intra-abdominal infection

Answer 351

Fungal asthma Travel associated fungal infections -Dimorphic fungi Post-influenza aspergillosis

Answer 352

Less than 150m Much of this cost is prophylaxis or empirical treatment of possible invasive fungal disease due to poor diagnostics.

Answer 353

Radiology Microscopy Culture Molecular

Answer 354

PCR – mixed results Antigen tests -Cryptococcal Ag - excellent -Galactomannan - insensitive -1,3 Beta-D-glucan – poorly specific

Answer 355

R - Insensitive in early stages M - Usually insensitive C - OK for yeasts, poor for moulds

Answer 356

achieve inhibitory levels of agent at the site of infection without host cell toxicity

Answer 357

Target does not exist in humans Target is significantly different to human analogue Drug is concentrated in organism cell with respect to humans Increased permeability to compound Modification of compound in organism or human cellular environment Human cells are “rescued” from toxicity by alternative metabolic pathways

Answer 358

Generally much more difficult for fungi than bacteria because they are eukaryotic More challenging to treat fungi than bacteria – more similar to out own cells – eukaryotic Trying to kill invading cell without killing normal host cell

Answer 359

DNA/RNA synthesis, protein synthesis - similar to mammalian - Use Flucytosine Cell wall - mannoproteins Β1,3 glucan Β1,6 glucan chitin Doesn’t exist in humans Echinocandins used to attack cell wall Plasma membrane: ergosterol Human cell membrane contains cholesterol not ergosterol Amphotericin Azoles Terbinafine are used

Answer 360

is very broad spectrum with a high barrier to resistance but: IV only Adverse effects+++ (reduced but not eliminated by expensive liposomal formulations) Renal, biochemical disturbance, infusion reactions Intravenous – has severe adverse effects – effectively forms a pore in the membrane – leach out salt and membrane protein – nephrotoxic drug – can lead to infusion reaction when first added Not first line therapy anymore

Answer 361

Echinocandins are safe and effective drugs against Candida with some activity against Aspergillus but are IV only Target cell wall – enzyme of cell wall – used in ITU and haematology – active against vast majority of candidates – really safe – intravenous only – safe and effective drugs – primarily used

Answer 362

Azoles are the mainstay of antifungal therapy currently Different drugs have different spectrum of activity Important toxicities and drug-drug interaction to be aware of Main stay is the azoles – broad class of drugs – been around for decades – earlier azoles where Important class of drugs to know about

Answer 363

Relatively safe All associated with transaminitis and GI SEs -Rare severe hepatitis Alopecia with long term fluconazole GI symptoms more pronounced with Itra -Nausea, abdominal pain, diarrhoea -Discontinuation of drug in 10% -Rare life threatening liver failure Voriconazole associated with reversible visual disturbance in 30% Photosensitivity in 1-2% of patients receiving voriconazole and recent reports of skin malignancy

Answer 364

Largely a result of cytochrome P450 isoforms

Answer 365

potent CYP3A4 inhibitor As above + steroids, statins, rifamycins,PIs

Answer 366

hydrophilic and the wat its principally excreted unchanged – less significant interactions Warfarin, phenytoin, calcineurin inhibitors, anxiolytics

Answer 367

Posaconazole is only a mild CYP3A4 inhibitor.

Answer 368

Common Caused by dermatophyte moulds Trichophyton rubrum is most common Broad differential diagnosis Microscopy is most specific test but 30% culture negative Topical success best in children with thin nails and less than 50% of plate involved. Amorolfine has an approximately 20% complete cure rate Non-dermatophytes on culture often just colonising

Answer 369

Slightly depressing Results of sampling can be confusing Limited treatment options Topical amorolfine Systemic itraconazole or terbinafine Treatment takes ages High failure rate with all therapies

Answer 370

Cell wall component of many fungi including common ascomycetous pathogens and Pneumocystis i.e. not zygomycetes or basidiomycetes Released into serum during invasive infection Assay very prone to contamination (80pg/ml cut-off) Non-specific for individual fungi

Answer 371

Infection/colonisation of healthy people frequent and occurs early in life Disease develops only with moderate-severe immunocompromise esp. HIV, transplant, steroids Frequent clinical presentation of unknown HIV Think about Pneumocystis when a patient has hypoxia more severe than CXR would suggest especially if gradual onset illness or risk factors.

Answer 372

Co-trimoxazole (plus steroids if hypoxic) is first line treatment

Answer 373

38.4 million

Answer 374

1.5 million

Answer 375

About 58% are in sub-Saharan Africa About 430 are among children under 15 years of age About 3600 are among adults aged 15 years and older, of whom: ─ almost 49% are among women ─ about 31% are among young people (15–24) ─ about 19% are among young women (15–24)

Answer 376

Anything more than 500

Answer 377

amount of HIV in your blood

Answer 378

global target of -90% of people living with HIV being diagnosed -90% diagnosed on ART (antiretroviral therapy) -90% viral suppression for those on ART by 2020

Answer 379

Global partnership between 90 high HIV burden cities where everyone works together to tackle HIV

Answer 380

Decreasing

Answer 381

Gay / bisexual men

Answer 382

Sexual Vertical – mother to child transmission Blood – don’t see much of this because of blood screening in the country

Answer 383

Undetectable = Untransmissable signifies that those who receive effective antiretroviral therapy and have achieved and maintained an undetectable viral load cannot transmit the virus to a sexual partner.

Answer 384

Pre-exposure prophylaxis of HIV (PreP) Taking HIV tablets b4 sex Take a pill a day or as in when (on demand) – 2-4 hours before sex

Answer 385

Several RCTs have reported on PreP; providing evidence for the effectiveness of daily dosing and event-based dosing Effectiveness has been demonstrated in MSM (men who have sex with men), heterosexual serodifferent couples, and injecting drug users

Answer 386

Post-exposure prophylaxis PEP = 28 days Combination Antiretroviral Therapy –must be started within 72 hours Not as effective as PreP

Answer 387

Access to appropriate treatment and care Reduction in morbidity and mortality Reduction of vertical transmission Reduction of sexual transmission Public health /partner notification Cost-effective

Answer 388

Clinician initiated diagnostic testing triggered by clinical indicators of immuno-suppression disease /seroconversion Routine screening in high prevalence locations Antenatal screening Screening in high risk groups Patient initiated requests for testing

Answer 389

They don’t think of HIV Underestimate the risk of HIV in their patients Failure to recognise HIV as a modifiable prognostic indicator Misconception they need pre-test counselling Misunderstanding of the implications for insurance, etc Fear of offending the patient

Answer 390

Generalised lymphadenopathy Acute generalised rash Glandular fever/ flu-like illnesses Think about seroconversion Oral candida Unexplained weight loss or night sweats Persistent diarrhoea Gradually increasing shortness of breath and dry cough Recurrent bacterial infections including pneumococcal pneumonia

Answer 391

Multi-dermatomal shingles Unexplained lymphadenopathy Unexplained wt loss or diarrhoea, night sweats, PUO Oral/oesophageal candidiasis or hairy leukoplakia Flu-like illness, rash, meningitis Unexplained blood dyscrasias

Answer 392

Venous blood sample is preferred Point of care test

Answer 393

Africa HIV-1 and HIV 2 similar to retro viruses found in monkeys in Central and West Africa First documented sample from infected human was from DR Congo in 1959 Bushmeat markets in West and central Africa are a potential route of transmission of simian retroviruses

Answer 394

Natural model of HIV control or “functional cure”: 35-40% are “elite controllers”, who maintain undetectable viral load for a decade or more and have a normal lifespan

Answer 395

Small RNA virus (~ 10KB): expresses just 10 genes Member of retrovirus family (uses reverse transcriptase to make DNA copy of itself) Lentivirus: characterized by long incubation period

Answer 396

-Glycoproteins on the HIV molecule (gP160 made of gP120 and gP 41) allow it to dock and fuse onto the CD4 and CCR5 receptors - HIV fuses to CD4 receptor and passes its contents into the CD4+ cell -The viral capsid the enters the cell and enzymes and nucleic acid are released -Using reverse transcriptase single stranded RNA is converted into double stranded DNA -Viral DNA then is integrated into the cells own DNA by integrase enzyme -When the infected cell divides the viral DNA is read and long chains of viral proteins are made -The viral protein chains are cleaved and reassembled -Budding here immature virus pushes out of the cell taking with it some cell membrane -Immature virus breaks free to undergo more maturation -Maturation protein chains in the new viral particle are cut by the protease enzyme into individual proteins that combine to form a working virus

Answer 397

GAG, POL, ENV - Structural TAT, REV - REGULATORY VPR, VIF, VPU, NEF - Accessory

Answer 398

encodes the enzymes: reverse transcriptase, integrase and protease

Answer 399

encodes the envelope proteins

Answer 400

increases infectivity

Answer 401

contributes to viral replication. Enhances production of host transcription factors e.g NF-kB.

Answer 402

encodes structural proteins. Made as a polyprotein and cleaved by HIV protease

Answer 403

binds to viral RNA and allows export from nucleus and also regulates RNA splicing

Answer 404

are CCR5 and CXCR4 chemokine receptors. CCR5 is used by HIV-1 in early infection, may switch to use CXCR4 later in infection. Once viral integration has occurred, infection persists for life in a reservoir of latently infected cells.

Answer 405

1% of Caucasians are homozygous for a 32bp deletion in the CCR5 gene (CCR5D32) necessary for primary HIV-1 infection People with only one copy of the mutant gene can be infected with HIV but show delayed disease progression It has been hypothesised that the origin in Caucasians could be related to protection from the Plague

Answer 406

Mutates rapidly HIV-1 shows huge viral sequence diversity that is increasing over time

Answer 407

Error-prone replication (the enzyme reverse transcriptase makes at least 1 error in every replication cycle) Rapid viral replication (generation time ~2.5 days) Large population sizes (~1010 new virus particles produced each day)

Answer 408

Acute HIV infection is early stage of HIV where there is a peak of viremia It is characterized by high viral load Immune responses during acute HIV infection are important for subsequent viral control Detection of very high levels of virus in the blood Symptoms of Acute Retroviral Syndrome: “Glandular fever”-like illness Fever, lymphadenopathy Sore throat, oral ulcers Skin rash (upper trunk) May include neurological features

Answer 409

Reduced risk of transmission Smaller reservoir, lower set-point, delayed progression

Answer 410

HIV is integrated into the DNA of the infected CD4-expressing cells HIV infects a range of CD4 + immune cells in addition to helper T-cells, (including regulatory T-cells, T follicular helper cells, dendritic cells, macrophages and thymocytes) However, the number of HIV-infected CD4+ T-cells in the blood does not explain the extent of immune suppression HIV can pass directly from cell to cell, and so it is relatively inaccessible to antibodies in the blood The small HIV genome encodes a range of genes that enable the virus to evade human immune system responses Immune system is constantly activated by HIV

Answer 411

Activated T-cells in the blood, correlated better with disease progression than viral load or CD4 count Early in HIV infection, there is a dramatic loss of CD4+ T-cells in the lymphoid tissue in the gut: this makes the gut mucosa leaky, allowing passage of bacteria and products (like LPS), stimulating immune cells and setting up a cycle of chronic immune activation that ultimately exhausts the immune system Immune activation is also driven directly by HIV, e.g. through a form of inflammatory cell death (pyroptosis), and co-infections, particularly with cytomegalovirus (CMV)

Answer 412

-Immune system generates a massive immune response to HIV infection, involving up to 20% of all circulating T and B lymphocytes -Antibodies develop against most viral proteins, but neutralising antibodies take months to develop and rarely neutralise the primary HIV strains that are transmitted from person to person - key immune response to HIV-1, from CD4+ T-helper cells, is lost from very early in infection, because these are the cells HIV infects first -vigorous response from cytotoxic CD8+ T-cells, which provides the major force controlling viral replication but ultimately fail when “immune exhaustion” sets in

Answer 413

surface of the virion is derived from the host cell membrane containing only a few (6 – 10) envelope spikes

Answer 414

is heavily glycosylated (with sugars resembling human types), which makes it difficult for antibodies to bind to the surface

Answer 415

-really critical parts of the viral envelope that are needed to enter CD4+ T-cells are either in deep pockets overhung by sugar molecules or only revealed when the virus docks onto the CD4 molecule -The envelope (gp120/41) proteins can change substantially without affecting virus function -Thus the virus can evolve very quickly to avoid antibody recognition (including by the addition of more sugar molecules) -HIV has small number of spikes on cell surface – enough to get into cells but not so many so that we can make antibodies against it and its antigen

Answer 416

circulating neutralising antibodies rarely recognise their own prevailing viral envelope variants`

Answer 417

generate broadly neutralising antibodies (BNAbs) that can neutralise multiple HIV strains Involves considerable somatic mutation of the antibodies (50+ mutations from the original antibody), so hard to generate with a vaccine

Answer 418

-CD4 binding site -Membrane-proximal region -V2V3 conformational epitope -Envelope glycans Potential use in therapy and to prevent infection

Answer 419

CD8+ cytotoxic T-cells identify cells expressing foreign material (from pathogens or tumours), processed as small fragments of protein (8-11 amino acids in length), presented on the surface of the infected cell by HLA class I molecules

Answer 420

Different HLA class I molecules are able to present peptides with different characteristics: a set of three distinct HLA class I molecules (A, B & C) are inherited from each parent These peptides can come from any part of a pathogen, so include more conserved structural and functional internal proteins (whereas antibody recognition is largely limited to surface proteins)

Answer 421

Recognition triggers the release of soluble anti-viral factors and the death of the infected cell Cytokines – soluble anti-viral factors CC- chemokines (compete with HIV for the receptor CCR5) Cytotoxic factors – kill the cell

Answer 422

CTL appear early in HIV infection, coincident with rapid drop in viral load CTL exert sufficient selection pressure on the virus for variants which escape CTL recognition to emerge CTL selection leads to HLA-class I associated “foot-prints” on viral evolution

Answer 423

HLA class I molecules associated with good outcome

Answer 424

HIV can evolve to escape T-cell recognition at several points on the antigen processing and presentation pathway Mutant HIV variants that evade the T-cell response appear within weeks of primary HIV infection Initially responses develop to the new variants but these are progressively undermined by the failure of CD4+ cell help and dendritic cell function

Answer 425

-Protein that reduces cell-surface expression of HLA class I molecules needed for CTL recognition, whilst at the same time upregulating the “death” molecule Fas that can kill virus-specific CTL before they can kill the virus-infected cell -HLA- A and B molecules are down-regulated to undermine CTL killing of infected cells but HLA-C expression is maintained to prevent NK cell killing -Ultimately CTLs develop functional “exhaustion”, associated with expression of inhibitory molecules such as PD-1: levels of expression correlate with viral load

Answer 426

10-11 years

Answer 427

defined as survivors with HIV-1 infection for >7-10 years, no therapy no symptoms stable CD4+ T-cell count > 500mm3 RARE - around < 1-5 % of cohorts

Answer 428

-Defined as HIV-1 infected individuals with plasma VL <50 copies/ml for over one year without ART: VERY RARE - 0.35-0.8% of cohorts -General but not complete overlap: controllers may progress to AIDS even with low viral load, LTNPs may have high Viral load: most eventually develop disease -Strongly associated with HLA class I alleles, but generally not distinguished by stronger or better immune responses (except preserved HIV-specific CD4+ IL-2+ responses)

Answer 429

Issues of adherence, side-effects, drug resistance Increase in non-AIDS-defining illnesses (NADIs): lung, cardiovascular and renal disease Incidence of NADIs is related to: -Size of latent HIV reservoir -Persistent immune activation -CMV co-infection

Answer 430

Even with the most effective available ART, a poorly-defined reservoir of latently-infected cells persists for years, and HIV starts replicating again (to pre-treatment levels) within weeks of cessation of therapy HIV is thought to persist as DNA integrated into “resting” transcriptionally-silent CD4+ T-cells and other cells such as tissue macrophages and T follicular helper cells HIV may continue replicating in lymphoid tissue and other immune-privileged sites

Answer 431

With persistent immune activation, largely driven by translocation of microbial products across the gut (damaged gut-associated lymphoid tissue and leaky gut since primary infection)

Answer 432

Berlin patient - He is the only person on the planet who has been cured of HIV infection using the incredibly toxic treatments he was receiving for leukaemia. This case has given new hope but it has also raised some major ethical dilemmas.

Answer 433

sex workers and their clients, gay men and other MSM, people who inject drugs, transgender people - account for >70% new infections globally

Answer 434

Eastern Europe and Central Asia

Answer 435

People with HIV (PWH) are 30-50% more likely to die from Covid-19

Answer 436

1.5m new peole in 2021 Over 96% HIV infections occur in low and middle income countries (LMICs) 25.3m HIV-infected people live in Sub-Saharan Africa ~20% do not know their HIV status Access to anti-retroviral therapy (ART) for Prevention of Mother-To-Child Transmission of HIV for 81% pregnant women globally Treatment access has improved, with 69% HIV+ adults in Africa now on ART 1.7m children (<15 yrs) living with HIV 160,000 children born with HIV in 2021 In 2021 only 59% HIV+ children were on ART

Answer 437

50% of all new infections occurring world-wide are in 15-24 year olds (women mostly)

Answer 438

Sexual violence

Answer 439

In utero: transplacental, mostly during the third trimester Intra partum: exposure to maternal blood and genital secretions during delivery Breast milk: ingestion of large amounts of contaminated milk In breast-feeding populations, risk of mother-to-child transmission (MTCT) is up to 45% Transmission can largely be prevented by ART given to pregnant women and to the infant (MTCT)

Answer 440

HIV is a lentivirus that uses reverse transcriptase to replicate (retrovirus) HIV replicates within CD4 cells, and over time decimates their population causing immunodeficiency HIV viral load increases over time Uses protease and integrase as well

Answer 441

1. CD4 cell count 2. HIV viral load Both are important in the prognosis

Answer 442

Red, blotchy areas, some flat and raised bits

Answer 443

From point of infection, usually takes 2-4 weeks to develop symptoms (acute HIV syndrome) During the acute HIV syndrome, HIV replicates rapidly, and CD4 cell count drops (as they are used by HIV to replicate within). The huge viraemia these patients experience is what causes their symptoms…

Answer 444

Glandular fever Flu

Answer 445

Fever Sore throat Myalgia Rash Vomiting + diarrhoea Headache Lymphadenopathy Weight loss Encephalitis Aseptic meningitis

Answer 446

Ask about sexual history Think of HIV seroconversion

Answer 447

5-10 years the immune system will start to take back control and the CD4 cell population increases, and the viral load temporarily decreases However, over time the CD4 population will slowly decline until the person is immunosuppressed enough to present with constitutional symptoms and opportunistic infections No symptoms! May notice some enlarged lymph nodes > Persistent Generalised Lymphadenopathy

Answer 448

Persistent Generalised Lymphadenopathy is defined as enlarged lymph nodes involving at least 2 areas of the body for at least 3 months

Answer 449

-Shingles (reactivation of chickenpox virus) -Thrush -Candida -Oral hairy leucoplakia - similar to thrush - white areas on tongue - cant scrape it off - assosciated with Epstein barr virus - Molluscum contagiosum - more common in kids

Answer 450

In an unexpected patient That is recurring That has no clear underlying cause

Answer 451

CD4 <200 or “AIDS defining illness” present - TB for eg

Answer 452

Bihilar infiltrates Very fine white areas in chest x rays Sometimes you can also get normal x ray Fevers, SOB, dry cough, pleuritic chest pain,exertional drop in oxygen saturations The most common AIDS defining illness 42.6% prevalence in AIDS Key feature is an exertional drop in oxygen saturations Fungal Check severity using arterial blood gas

Answer 453

Fungal, but susceptible to some antibiotics! Co-trimoxazole +/- prednisolone (steroids) if hypoxic Co-trimoxazole is first line = 2 antibiotics: trimethoprim + sulfamethoxazole Also called septrin

Answer 454

Increased transmission Increased morbidity Increased mortality

Answer 455

All patients with TB require a HIV test TB in HIV at any CD4 count: AIDS defining Atypical presentations with lower CD4 count Sample for Acid Fast Bacilli staining AIDS defining illness

Answer 456

Tuberculoma: Ring enhancing lesion which can have surrounding oedema Most common Can be a single mass with surrounding oedema or multiple small masses as part of military TB CSF analysis often helps in establishing the diagnosis Treated with 12 months TB treatment Ocular TB: TB can occur anywhere in the eye Can involve any part of the eye (Eg. Uveitis, retinal, orbit, external eye) and can occur with or without evidence of systemic TB. It generally develops following haematogenous spread from a primary focus but, in rare cases, it can also occur as a primary infection following an epithelial injury.

Answer 457

Can occur in non-HIV but much higher incidence and mortality in the HIV population Variable presentation from an acute meningitis to a progressive dementia Cranial nerve palsies (most commonly 6th nerve) Insidious onset of headache – variable 1 day – 6 months! Night sweats and fevers Vomiting Active pulmonary TB present in 30-60% of cases Without treatment proceeds to coma and death

Answer 458

Generally more likely to get any lymphoma due to the link with EBV Risk of having CNS lymphoma is over 1000x higher(!) if you have a HIV diagnosis compared to the general population Generally present with headaches and focal neurological symptoms depending on where in the brain the tumour is Usually a single lesion and ring enhancing Ultimately diagnosed on biopsy

Answer 459

CNS toxoplasmosis is due to reactivation of latent infection (Seroprevalence 15-50%, acquired via cat contact or through contaminated meat or water) CD4 usually <100 Multiple ring enhancing lesions on MRI Treated with sulphadiazine + pyrimethamine (+folinic acid)

Answer 460

CNS toxoplasmosis is due to reactivation of latent infection (Seroprevalence 15-50%, acquired via cat contact or through contaminated meat or water) CD4 usually <100 Multiple ring enhancing lesions on MRI Treated with sulphadiazine + pyrimethamine (+folinic acid)

Answer 461

Most common place for CMV to reactivate in HIV is eyes Looks like a pizza Cytomegalovirus is a herpes virus, that causes a glandular fever type illness in the immunocompetent individual. If someone is immunosuppressed, they can get CMV pneumonitis, retinitis, encephalitis and colitis, but in HIV CMV retinitis seems to be the most common site of reactivation. Causes visual blurring and blindness. Doesn’t cause pain. Treated with antiviral agents (valganciclovir or ganciclovir)

Answer 462

Toxoplasmosis can also affect the eyes… in 1-2% of those with HIV Causes inflammation at the back of the eye (retina) and can cause pain, blurred vision and blindness Acutely there is a necrosising retinochoroiditis If the optic nerve is affected, direct spread can occur into the brain Intravitreal antibiotics can be given in addition to systemic.

Answer 463

Cryptococcus is a yeast like fungus that can cause a meningitis in those who are immunocompromised. Usually presents with a gradual onset headache and fever (weeks) Little to find on examination and CT LP – very high opening pressure (>40cm H2O) India ink stain to visualise on microscopy, a “halo” appears around the cryptococci due to the polysaccharide capsule Treat with Amphoteracin B + flucytosine and serial LPs Gradual onset headache / fever High opening pressure on lumbar puncture India ink used on microscopy

Answer 464

Lumbar puncture

Answer 465

Virus eg Human Herpesvirus 8 > Kaposi’s sarcoma Epstein Barr Virus > Lymphomas Human Papillomavirus > Cervical, anal, penile carcinoma Hepatitis B/C > Hepatocellulcar carcinoma

Answer 466

Kaposi's sarcoma Lymphomas Cervical cancer

Answer 467

Human Herpesvirus 8 Usually associated with HIV Single or multiple lesionsUsually on the skin Treated with HAART and chemo/radiotherapy Kaposi’s usually indicates underlying HIV infection, however can rarely can be genetic Spectrum of disease – single to multiple lesions Other sites – mouth, GI tract  GI bleed, respiratory tract Can cause bleeding

Answer 468

HAART (Highly Active Anti-Retroviral Therapy) 3+ antiretroviral drugs NIRT + NIRT + OTHER Act on different pointsin replication cycle tosuppress viral replication Aim to reduce viral load to undetectable levels and increase CD4 count

Answer 469

Entry inhibitors e.g. Maraviroc Fusion inhibitors e.g. Enfuvirtide After HIV enters the cell, it uses reverse transcriptase to transform from RNA to DNA. Our next two classes of ARVs inhibit reverse transcriptase to block this step. 3. NRTIs: Nucleoside reverse transcriptase inhibitors (-dines and -bines) - most HAART regimes are made up of a back bone of 2 NRTIs) and NNRTIs: Non-nucleoside reverse transcriptase inhibitors.

Answer 470

The viral DNA then uses integrase to integrate its genome into the host cell’s DNA. This gives us another opportunity to block HIV replication with… 4. Integrase inhibitors “INSTIs” (-gravir) e.g. raltegravir, these are now used frequently as the 3rd agent within HAART, as they result in a rapid reduction of the viral load. Excitingly there are some new injectable INSTIs that can be used.

Answer 471

After hijacking the nuclear DNA, the RNA product then uses protease to exit the CD4 cell. 5. Protease inhibitors block HIV proteases to prevent HIV becoming a mature virion (–navir) e.g. darunavir. They are often given with a “boosting” agent. These used to be widely used, however they are associated with increased risk of CV events, so many patients have switched to other agents due to the aging population of patients with HIV.

Answer 472

With current HAART regimes, HIV infection is an entirely manageable condition with a good prognosis!

Answer 473

1 mutation in every 2 new viruses produced 1 -10 billion new virus particles each day 1-5 billion mutations per day 1. Non adherence - missing doses or taking meds late 2. Drug - drug interactions eg - Decreased drug levels a) Clopidogrel + Boosted PI = ↓ clopidrogel active metabolite b) Lansoprazole + Rilpivirine = reduced rilpivirine levels +/- resistance - Increased drug levels a.Steroids + Ritonavir = risk of Addisonian crisis b.Recreational drugs + antiretroviral boosting agents = toxicity

Answer 474

suppress HIV replication avoid drug resistance ALWAYS CHECK DRUG INTERACTIONS

Answer 475

Toxins Streptolysins O&S -binds cholesterol Erythrogenic toxin -Streptococcal pyrogenic toxin e.g. SPeA – exaggerated response

Answer 476

Toxins Streptolysins O&S -binds cholesterol Erythrogenic toxin -Streptococcal pyrogenic toxin e.g. SPeA – exaggerated response

Microbiology Flashcards

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