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Sera's MBBS > Micro > Flashcards

Micro Flashcards

1
Q

Reportable GI infections for public health

A

campylobacter, salmonella, shigella, E.Coli 0157, Listeria, Norovirus

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2
Q

B-LACTAMS MOA

A
  • Work by inactivating the enzymes involved in the terminal stages of cell wall synthesis (transpeptidases also known as penicillin binding proteinsB)
  • Beta-lacktam is a structural analogue of the enzyme substrate
  • Bactericidal
  • Active against rapidly-dividing bacteria
  • Do not work with bacteria that do not have peptidoglycan - mycoplasma and chlamydia

MOA

  • Transpeptidase forms peptide crosslinks between NAM and NAG of the peptidoglycan
  • Impt for structural integrity and also sometimes confer virulence
  • Hence daughter cells have weakened cell wall, undergoes osmotic lysis and dies
  • They do not ‘punch holes’ in the cell wall (because they do not affect bacterial cells that are not actively dividing)
    • Hence they are unable to kill non-actively dividing bacteria
      • Cell cycle whereby there is lack of nutritions and they do not actively divide e.g. in a big abscess
      • Biofilms on prostatic material
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3
Q

4 main classes of beta-lactams Abx

A
  1. Penicillin
  2. Cefalosporins (cefotaxmine)
  3. Carbapenems (imipenem)
  4. Monobactams (carumoam)
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4
Q

Carbapenems examples

A
  • Meropenem, Imipenem, Ertapenem
  • But carbapenemase enzymes becoming more widespread, hence concerns about antibiotic resistance as this is currently the last line
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5
Q

GLYCOPEPTIDES MOA

A

e. g. vancomycin and teicoplanin
* Large molecules that inhibit cell wall synthesis
* But unable to penetrate Gram-ve outer cell membrane (LPS layer)
* Only active against Gram+
* Important for treating serious MRSA infections (Iv only)
* Slowly bactericidal
* Nephrotoxic - hence important to monitor drug levels to prevent accumulation

MOA

  • Binds to the peptide linked between the peptidoglycan precursors
  • And prevents transpeptidase and transglycosidase from being able to bind
  • Hence prevents cell wall from getting peptide or glycosidic bonds = weak cell wall
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6
Q

Inhibitors of protein synthesis (bind to bacterial ribosomal subunits) (5)

A
  • Aminoglycosides (30S)
  • Tetracyclines (30S)
  • Macrolies (e.g. erythromycin), Lincosamids (clindamycin), Streptogramins (Syncercid) - MSL group (50S)
  • Chloramphenicol (50S)
  • Oxazolidinones (e.g. Linezolid) (50S)
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7
Q

Oral vanc

A

Used to treat C.diff

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8
Q

AMINOGLYCOSIDES MOA and examples

A
  • Bind to amino-acyl site of 30S ribosomal subunit
  • Rapid, concentration dependent bactericidal action
    • Hence usually given in big doses to kill bacteria
  • Require specific transport mechanisms to enter cells (accounts for some intrinsic resistance)
  • Ototoxic and nephrotoxic, therefore must monitor levels
  • Gentamicin and tobramycin particularly active against Ps. aeruginosa
  • Synergistic combination with b-lactams
  • No activity against anaerobes

MOA

  • Binds 30S ribosomal subunit
  • Prevent elongation of polypeptide chain
  • Cause misreading of the codons along the mRNA
  • But full MOA is not understood

e.g. gentamicin

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9
Q

TETRACYCLINE MOA and example

A
  • Broad-Spectrum but activity being reduced by increasing resistance as well
  • Bacteriostatic
  • Particularly useful for intracellular pathogens (chlamydia, rickettsiae and mycoplasma)
  • Deposits in growing bone (hence not given to children) or pregnant women (tetragenic)
  • Also causes light-sensitive rash

MOA

  • Reversibly bind to 30S ribosomal subunit
  • Prevent binding of aminoayl-tRNA to the ribosomal acceptor site so inhibiting protein synthesis

example doxycycline

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10
Q

MACROLIDES MOA and example

A
  • Bacteriostatic
  • Minimal activity against Gram-, because they can’t cross outer membrane LPS
  • Useful for treating mild Stap or Strep in penicillin allergic pts
  • Active against Campylobacter and Legionella penumophillja (hence given to cover atypical in pneumonia)
  • Newer agents include clarthromycin and azithromycin with improved pharmacological properties

MOA

  • Bind to 50S subunit
  • Stimulate dissociation of peptidyl-tRNA
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11
Q

CHLORAMPHENICOL MOA + SE

A
  • Bacteriostatic
  • Very broad antibacterial activity
  • Rarely used because of risk of aplastic anaemia and grey baby syndrome in neonates because of inability to metabolise the drug

MOA
* Bind 50S subunit, protein synthesis

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12
Q

OXAZOLIDIONES (LINEZOLID)

A
  • Binds to 23S component of 50S
  • Highly activate against Gram+ including MRSA and VRE
  • Not active against most Gram-ve
  • Very expensive, may cause thrombocytopenia and should be used with consultant micro/ID approval
  • This the first class of completely synthetic Abx
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13
Q

Inhibitors of DNA synthesis (2)

A
  • Quinolone e.g. ciprofloxacin, levofloxacin, moxifloxacin

* Nitroimidazoles e.g. methronixadole and tinidazole

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14
Q

QUINOLONES MOA and examples

A
  • Bactericidal
  • Broad anti-bacterial activity especially against Gram-ve (cipro for pseudomonas)
  • Newer against (e.g. levofloxacin and moxifloxacin) have increased activity against Gram+ve and intracellular bacteria but less activity against Pseudomonas
  • Well absorbed following oral administration
  • Used for UTI, pneumonia, atypical pneumonia and bacterial gastroenteritis
  • Against increased resistance, decreasing utility

MOA
* Act on DNA gyase predominantly

e.g. ciprofloxacin, levofloxacin, moxifloxacin

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15
Q

NITROIMIDAZOLE (METRONIDAZOLE) MOA

A
  • Rapidly bactericidal
  • Used for anaerobes and protozoa
  • Nitrofurans are related pounds: nitrofurantoin is useful for treating simple UTIs

MOA
* Under anaerobic conditions, active intermediate causes DNA strand breakage

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16
Q

RIFAMPICIN MOA

A
  • Bactericidal
  • broad spectrum
  • Active against certain bacteria including mycobacteria and chylamydia
  • Metabolised by the liver and can cause drug-drug interaction (contraceptive) and monitor LFT
  • May turn urine and tears orange

MOA
* Binds to RNA-dependnet RNA polymerase and inhibit initiation of transcription

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17
Q

Rifampicin SE and resistance

A

Resistance for rifampicin

  • Altered targets
  • Resistance to rifampicin develops rapidly, can develop while on treatment
  • Should never be used as single agent except for short-term prophylaxis
  • Chromosomal mutation causes a single amino acid change i the beta-submit ofRNA polymerase which than fails to bind rifampicin

orange secretions (tears and urine)

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18
Q

Cell membrane toxins (2)

A

Daptomycin

  • Cyclic lipopeptide used to treat MRSA and VRE
  • Recent, new drug
  • Gram+ve

Colistin

  • Polymyxin antibiotic, activate against Pseudomonas, Acinetobacter baumannii and Klebsiella penumoniae
  • Old drug
  • Not absorbed by mouth
  • Nephrotoxic and should be reserved for use against MDR bacteria
  • very difficult to dose due to SE
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19
Q

Inhibitors of folate metabolism (2)

A
  • Sulfonamides

* Diaminopyrimidines (e.g trimethoprim)

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20
Q

MOA of * Sulfonamides

* Diaminopyrimidines (e.g trimethoprim)

A
  • MOA: folate inhibitors
  • Synergistic action between the two drug classes because they act on sequential stages of folate pathway
  • Combination = co-trimoazole
  • Trimethoprim used to treat community acquired UTIs
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21
Q

Resistance - * MRSA (methicillin resistance S.aureus)

A
  • mecA gene encoded novel PBP2a
  • Low affinity for binding beta-lactam
  • Substitutes for the essential functions of high affinity PBP at otherwise lethal concentrations of antibiotic
  • Hence they are resistant to ALL Pencillin because this alternate pathway
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22
Q

Resistance - Strep pneumo

A
  • Result of acquisition of stepwise mutation in PBP
  • hence slight increase in resistance
  • But lower level resistance be overcome by increasing dose
  • Problem because strep pneu can cause meningitis because the slight increase in resistance will not respond to benzylbenicillin typically used to bacterial meningitis as they do not accumulate high enough conc in CSF
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23
Q
  • When prescribing gentamin, what is the most important factor to maximise?
A
  • gent is amino glycoside, therefore Cmax is most important → Dose/peak above MIC
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24
Q
  • What PK/PD perimeter is the most important in penicillin dosing?
A
  • Pencillin is trough dependent/time dependent → duration>MIC
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25
Q

C.diff colitis what abx

A

Stop offending abx
PO metronidazole
if fail than PO vancomycin

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26
Q

Hospital acquired UTI

A

Cephalexin/augmentin

If infected urinary catheter: change under gentamicin cover

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27
Q

hospital acquired pneumonia

A

Cephalosporin + ciprofloxacin + tazocin (covering for pseudomonas)
If MRSA risk, add vancomycin (IV)

  • 1st line: ciprofloxacin ± vancomycin
  • 2nd line: tazocin + vancomycin
  • Specific therapy:
    1. MRSA: vancomycin
    2. Pseudomonas aeruginosa: tazocin OR ciprofloxacin ± gentamicin
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28
Q

community acquired pneumonia

A
  • Mild-moderate: amoxicillin OR erythromycin/clarithromycin
  • Moderate-severe:
    1. Hospital admission required
    2. Augmentin + clarithromycin
    3. If allergic to penicillins: cefuroxime + clarithromycin
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29
Q

Pharyngitis

A

Benzylpenicllin

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30
Q

Atypical pneumonia do not have cell wall hence pencilling do not work therefore give

A

Marcolides e.g. erythromycin or azithromycin

tetracyclines e.g. doxycycline

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31
Q

Staph aureus: food poisoning

A
  • Properties:
    1. Catalase & coagulase +ve
    2. Gram +ve cocci appear in tetrads & clusters
    3. Form yellow colonies on blood agar
    4. Produces enterotoxin: exotoxin superantigen acting on GIT, stimulating IL-1 & IL-2
  • 1/3 population are chronic carriers, 1/3 are transient
  • Spread by skin lesions on food handlers
    • Skin cells shed into the food
    • Because it is a pre-formed toxin, hence effects (D&V) occurs rapidly after consumption within 2-7hours
  • Causes prominent, vomiting and watery non-bloody diarrhoea
  • Don’t treat, self limited
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32
Q

Bacillus cereus: food poisoning

A
  • Properties:
    1. Gram +ve rods which produce spores
    2. Produce 2 toxins (preformed): heat stable emetic toxin (not destroyed by reheating) & heat labile diarrhoeal toxin (present if food not cooked to high enough temp.) → hence again symptoms occur rapidly after consumption
  • Bacterial produces spores which geminate in reheated fried rice
  • Watery non-bloody diarrhoea, self-limiting
  • Rare cause of bacteraemia and cerebral abscesses in vulnerable population
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33
Q

Clostridia - Gram+ anaerobe

A
  • Clostridium botulinum: botulism
    • Source: canned or vacuum packed food (honey/infants)
    • Ingestion of preformed toxin (inactivated by cooking)
    • Blocks ACh release from peripheral nerve synapse → Sx of paralysis
    • Treatment with anti-toxin
  • Clostridium pefringens: food poisoning
    • Source: reheated food (meat)
    • Normal flora of colon (but not small bowel) where the enterotoxin acts (super antigen)
    • Incubation 8-16hrs
    • Watery diarrhoea, cramps, little vomiting lasting 24hrs
  • Clostridium difficile: pseudomembranous colitis
    • 30% of hospital pts, 3% of community
      • <2 and >65 may just carry C.diff without producing toxins and asymptomatic
    • Antibiotics related:
      • 4Cs: cephalosporins, cipro, clindamycin and co-amoxiclav
      • But any Abx can cause it
    • Able to spread by spores to environment and people
    • Infection control
    • Tx: PO metronidazole, vancomycin, (for local effects) stop antibiotics where possible
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34
Q

Listeria monocytogenes: febrile gastroenteritis outbreaks

A
  • Properties:
    1. Haemolytic
    2. Aesculin +ve
    3. Tumbling motility (like tumbleweed)
  • particularly in pregnant women
  • Source:
    • Refrigerated food i.e. unpasteurised diary, vegetables
    • Grows at 4oC (cold enhancement)
  • GI watery diarrhoea, cramps, headache, fever, little vomiting
  • Perinatal infection (listeria meningitis), immunocompromised pts
  • Treatment: ampicillin
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35
Q

Enterobacteriacae (E.coli)

A
  • E.coli
    • Properties:
      • Facultative anaerobes
      • Glucose/lactose fermenters (LF)
      • Oxidase negative
    • Enterotoxins:
      • Heat labile stimulus AC and cAMP
      • Heat stable stimulates GC
      • Acts of the jejunum, ileum not on colon
    • Source: food/water contaminated with human faeces
    • Serotypes
      ETEC - travellers diarrhoea
      EHEC - haemorrhagic O157 → HUS
      EPEC - infantile diarrhoea
      EIEC - invasive, causes dysentery (inflammatory diarrhoea. Above 3 all just secretory diarrhoea)
    • Avoid antibiotics (as they exacerbates condition, unknown MOA)
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36
Q

Enterobacteriacae (salmonella)

A

Enterobacteriacae (salmonella)

  • Properties:
    • Non-lactose fermenters
    • H2S producers (black bits), TSI agar, XLD agar, selenite F broth
    • Surface antigens
      • Cell wall O
      • Flagella H
      • Capsular Vi (virulence, antiphagocytic)
      • Depending of which type of O and H will tell you which strain of salmonella you have got
  • Three impt species:
    • S. typhi and parathyphi (more worrying)
    • S. enteritidis
    • S. cholerasuis

S.enteritidis (Enterocolitis)

  • Transmitted from poultry, eggs, meats
  • Invasion of epi- and sub-epithelial, tissue of small and large bowel
  • Don’t usually cause fever or bacteraemia
  • Usually not treated - self limited, non bloody diarrhoea (usually no treatment needed but cipro if required)
  • Stool positivity

S.typhi (thyphoid/enetric fever)

  • Transmitted only by humans (human to human) → human can be reservoir
  • Multiples in Peyer’s patches (not specific to sub-epithelial cells
  • Fever and bacteraemia
    • Particularly at risk if pt is sickle cell
    • 3% carriers
  • Slow onset, fever and constipation - NO DIARRHOEA
  • O/E: Splenomegaly, rose spots, anaemia, leucopenia, bradycardia, haemorrhage and perforation
  • Ix: Blood culture positive, leucopenia
  • Treatment: ceftriaxone
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37
Q

Enterobacteriacae (shigella)

A
  • Shigellae: dysentery
    • Properties:
      • Non-lactose fermenters
      • Non H2S producers (v salmonella)
      • Non-motile
      • Surface antigens
        • Cell wall O antigens
        • Polysaccharids (Groups A-D): S.sonnei, S. dysenteriae, S.flexneri (man have sex with men)
    • Most effective enteric pathogen (low ID 50)
    • No animal reservoir
    • No carrier state
    • Dysentery
      • Invading cells of mucosa of distal ileum and colon
      • Producing enterotoxin (Shiga toxin)
    • Avoid antibiotics (but ciprofloxacin if required) - similar to Salmonella enteritidis
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38
Q

Vibrios: massive diarrhoea

A
  • Properties:
    • Curved, comma shaped
    • Late lactose fermenters
    • Oxidase positive
  • Vibrio cholera
    • O1 group or non O1 group
    • O1 group = epidemics
    • Non O1 group = sporadic or non-pathogens
    • Transmitted by contamination of food and water form human faceless (shellfish, oyster, shrimp)
    • Colonisation of small bowl and secretion of enterotoxin with A and B subunit (AB toxin), causing persistent stimulation of adenylate cyclase
    • Causes massive diarrhoea (rice water stool) without inflammatory cell
    • Treat losses - fluid and electrolyte replacement
  • Vibrio parahaemoyticus
    • ingestion of raw or undercooked seafood
    • Major cause of diarrhoea in Japan
    • Self-limited in 3 days
    • Grows in salty 8.5% NaCl
    • treat with doxycycline
  • Vibrio vulnificus
    • Cellulitis in shellfish handlers
    • Fatal septicaemia with D+V in HIV pts
    • treat with doxycycline
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39
Q

Campylobacter:

A

Campylobacter:

  • Properties:
    • Curved, comma or S shaped
    • Microaerophilic - don’t require much oxygen
    • Oxidase +ve
    • Motile
  • C. jejuni grows at 42oC (most common campylobacter)
    • Transmitted via contaminated food and water with animal faeces (poultry, meat, unpasteurised milk)
    • Enterotoxin → watery diarrhoea, foul smelling diarrhoea, bloody stool, fever and debilitating abdo pain
  • Can lead on to GBS (Gillian Barre syndrome), react arthritis, Reiter’s syndrome
  • Self-limiting but symptoms can last for weeks (20 days)
  • Treat with erythromycin or cipro if within first 4-5 days but most pts would be over (self-limiting) by the time the results are back and don’t require treatment
  • Only treat if immunocompromised (macrolide)
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40
Q

Yersinia enterocolitica: enterocolitis and mesenteric adenitis

A
  • Properties:
    • Non-lactose fermenter
    • Prefers 4oC (cold enrichment)
  • Transmitted via food contaminated with domestic animals excitements e.g. cats
  • Enterocolitis
  • Mesenteric adenitis
  • Associated with reactive arthritis, Reiter’s
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41
Q

Entamoeba histolytia

A
  • motile trophozoite in diarrhoea
  • Non-motile cyst in non-diarrhoea illness
  • Killed by boiling, removed by water filters
  • 4 nuclei
  • No animal reservoir
  • Ingestion of cysts → trophozoites in ileum → colonic cecum, colon → Flask shaped ulcer
  • Symtoms
    • Acute: Dysentery, flatulence, tenesmus
    • Chronic: weight loss +/- diarrhoea
    • Liver abscess
  • Diagnosis
    • Stool micro (wet amount, iodine and trichrome stains)
    • Serology in invasive disease
    • Treat: metronidazole + paromomycin in luminal disease
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42
Q

Giardia lambda: non-bloody diarrhoea

A
  • Trophozoite, ‘pear shaped’
  • 2 nuclei
  • 4 flagellas
  • Ingestion of cyst from faecally contaminated water, food
  • Excystation at duodenum, trophozoite attaches, no invasion
  • Malabsorption of protein and fat
  • Travellers, hikers, day care, mental hospital & MSM
  • Presents withs:
    • Foul smelling non-bloody diarrhoea
    • Cramps
    • Flatulence
    • No fever
  • Diagnosis:
    • Stool micro
    • ELISA
    • “string test”
  • Treatment: Metronidazole
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43
Q

Cryptosporidium parvum: severe diarrhoea in immunocompromised

A

Cryptosporidium parvum: severe diarrhoea in immunocompromised

  • infects the jejunum
  • Ix: Oocysts seen in stool by modified Kinyoun acid fast stain
  • Self-limiting
  • Treatment: reconstitute of immune system. No real treatment for itself.
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44
Q

Norovirus

A

Norovirus

  • Low ID (18-1000 viral particles)
  • Environment resilience (0-60oC)
  • No long term immunity
  • Hence you can get it again and again = outbreaks
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45
Q

Rotavirus

A

Rotavirus

  • dsRNA ‘wheel like’
  • Affects children
  • Replicates in mucosa of small intestine
  • Secretory diarrhoea, no inflammation
  • Most children by age 6 have antibodies, exposure to natural infection confers lifelong immunity

Vaccinated:

Vaccines (viral)

  • Rotarix: live attenuated human strain, 2 PO dose
  • Rotateq: pentavalent, 3 PO doses, one bovine, and four human staring
  • Rotashield and intussusception (8-20 weeks)
  • Age of vaccine is 6-12 weeks
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46
Q

Adenovirus

A

Adenovirus

  • Types 40/41 causes non-bloody diarrhoea, <2years of age
  • Any type of diarrhoea in immunocompromised
  • Not so common in healthy non-immunocompromised
  • Diagnosis:
    • Stool EM, antigen detection, PCR
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47
Q

Common causes of encephalitis

A

Rabies virus, arbovirus, Trypanosoma species, Prions, Amoeba

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48
Q

Common cause of myelitis - infection of the spinal cord

A

Poliovirus

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49
Q

Clostridium tetani and clostridium botulinum causes neurotoxin syndrome - what are the symptoms?

A

Paralysis, rigidity (tetanus), or flaccid (botulism)

Affects CNS and PNS

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50
Q

Septicaemia - clinical spectrum produced by four processes

A

Capillary leak
→ Albumin and other plasma proteins leads to hypovolaemia

Coagulopathy
→ Leads to bleeding and thrombosis 
* Endothelial injury results in platelet-release reactions 
* Protein C pathway 
* Plasma anticoagulants

Metabolic derangement
→ Primarily acidosis

Myocardial failure
→ multi-organ failure

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51
Q

Cause of Chronic meningitis

A

TB

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52
Q

Causes of aseptic meningitis and diff in clinical presentation compared with bacterial meningitis

A

Aseptic meningitis

  • Most common infection of the CNS
  • Headache, stiff neck, photophobia
  • Non-specific rash
  • Coxsackievirus Group B and echoviruses responsible for 80-90% causes
  • Most frequently occurs in children <1 year
  • Clinical course is self-limiting and resolves in 1-2 weeks
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53
Q

Encephalitis v meningitis

A

Encephalitis

* Affects cognition

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54
Q

Leading cause of encephalitis worldwide

A

West Nile Virus - leading cause of encephalitis internationally

  • Originated in West Nile
  • And now additional outbreaks/common in US
  • Expected to reach UK soon
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55
Q

Bacterial cause of infectious encephalitis

A

Bacteria causes of infectious encephalitis

* Listera monocytogenes

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56
Q

Amoebic encephalitis

A

Amoebic encephalitis

  • Naegleria fowleri
  • Habitat - warm water
  • Acanthamoeba species and balamuthia mandrillaris
    • Brain abscess, aseptic or chronic meningitis
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57
Q

Brain infection in immunocompromised?

A

Toxoplasmosis

  • Obligate intracellular protozoal parasite, toxoplasma gondii
  • Via the oral, transplacental route or organ transplantation
  • Severe infection in immunocompromised pts
  • Affected organs include the grey and white matter of the brain, retina, alveolar lining of the lungs, heart and skeletal muscle
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58
Q

Interpret this CSF

  • clear fluid
  • raised white cell (lymphocytes predominant)
  • negative gram staining
  • very high protein
  • low glucose
A

Tuberculous meningitis

  • TB meningitis
  • Brain abscess
  • Cryptococcal meningitis

Not viral because of low glucose. Viral also usually have less slightly raised protein

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59
Q

20F, headache and neck stiffness, Gram + (red), alpha-haemolytic

A

Strep pneumonia

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60
Q

18M, headache neck stiffness, Gram- (purple) non-haemolytic

A

Neisseria meningitides

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61
Q

65y.o, headache, neck stiffness, Gram+, Anton test on Mueller-Hinton agar

A

Listeria monocytogenes

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62
Q

45, headache, neck stiffness, Ziehl-Nelson stain

A

TB

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63
Q

35, headache, neck stiffness India ink stain

A

Cryptoccocus
Indian ink is specifically for yeasts.
likely immunocompromised

Notes for cyptoccocus
* Pressure of 40cm water + india ink + immunocompromised

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64
Q

Generic Abx for ?meningitis

A
  • Ceftriaxone 2g iv bd
  • If >50 years or immunocompromised add: Amoxicillin 2g IV 4 hourly (to kill amox)

<3month/1 month add ampicillin for Listeria cover

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65
Q

Generic Abc therapy for meningo-encephalitis

A
  • Acyclovir 10mg/kg iv ads
  • Ceftriaxone 2g iv bd
  • If >50 years of immunocompromised add: Amoxicillin 2g IV 4 hourly
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66
Q
  • Which of the following cell types in a urine microscopy suggest a poor taken sample? - white cell, squamous cell or red blood cells
A

Squamous cell

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67
Q

Dipstick parameters product of nitrate reductase and suggestive of UTI

A

nitrites

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68
Q

Define the following terms: bacteriuria, cystitis, pyelonephritis, uncomplicated urinary tract infection, complicated urinary tract infection

A
  • Bacteriuria: the presence of bacteria in the urine
    • Is not significant (asymptomatic bacteriuria) except in pregnancy
  • Cystitis: inflammation of the bladder often caused by infection
    • More relevant
  • Pyelonephritis: is an inflammation of the kidney tissue, calyces, and renal pelvis. It is commonly caused by bacterial infection that has spread up the urinary tract or travelled through the bloodstream to the kidneys.
  • Uncomplicated UTI refers to infection in a structurally and neurologically normal urinary tract.
  • Complicated UTI refers to infection in a urinary tract with functional or structural abnormalities (including indwelling catheters and calculi)
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69
Q

What is complicated UTI and who gets them?

A

Complicated UTI refers to infection in a urinary tract with functional or structural abnormalities (including indwelling catheters and calculi)

  • Men - longer urethra, hence typically regarded as complicated
  • Pregnant women: coliforms are associated with pyelonephritis and more severe infections later in pregnancy
  • Children
  • Patients who are hospitalized or in health care-associated settings e.g. catheterisation
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70
Q

LO2: Recall the incidence of urinary tract infections

A
  • The prevalence of bacteriuria in young non-pregnant women is about 1 to 3%. Don’t always treat unless symptomatic
  • Up to 40% to 50% of the female population will experience a symptomatic UTI at some stage during their life.
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71
Q

LO: List the common bacterial causes of urinary tract infection

A
  • More than 95% of UTIs are caused by a single bacterial species
  • E. Coli is by far the most frequent infective agent

Other organisms

  • Only tend to cause infections with other abnormalities.
    • Proteus mirabilis- ax with kidney stones!!!!
    • Klebsiella aerogenes
    • Enterococcus faecalis
    • Staphylococcus saprophyticus: common cause in young women!!!
    • Staphylococcus epidermidi (introduced when there is procedures done e.g. long term catheters!!!
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72
Q

If pt gets recurrent UTI due to either structural abnormally, the relative frequency of UTI caused by these organisms increase compared to a healthy individual

A
  • In recurrent urinary tract infections, especially in the presence of structural abnormalities of the urinary tract, the relative frequency of infection caused by
    Proteus,
    Pseudomonas,
    Klebsiella, and
    Enterobacter species and
    by enterococci and staphylococci increases greatly
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73
Q

Antibacterial host defences in the urinary tract (3)

A
  • Urine (osmolality, pH, organic acids)
  • Urine flow and micturition
  • Urinary tract mucosa (bactericidal activity, cytokines).
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74
Q

LO: Recall the pathogenesis of, and risk factors for, urinary tract infection and pyelonephritis

A

Renal tract abnormalities

  • Several abnormalities of the urinary tract interfere with its natural resistance to infection.
  • Obstruction inhibits the normal flow of urine → stasis is important in increasing susceptibility to infection

Obstruction

  • Mechanical reasons
    • Extrarenal: valves, stenosis, or bands, calculi, extrinsic ureteral compression from a variety of causes and benign prostatic hypertrophy.
    • Intrarenal: nephrocalcinosis, uric acid nephropathy, analgesic nephropathy, polycystic kidney disease, hypokalaemia nephropathy and the renal lesions of sickle cell trait or disease.
  • Neurogenic malfunction
    • Poliomyelitis
    • Tabes dorsalis
      • Tabes dorsalis, also known as syphilitic myelopathy, is a slow degeneration (specifically, demyelination) of the nerves primarily in the dorsal columns (posterior columns) of the spinal cord (the portion closest to the back of the body).
    • Diabetic neuropathy
    • Spinal cord injuries

Reflux

  • Important in children
  • Vesicoureteral reflux tends to perpetuate infection by maintaining a residual pool of infected urine in the bladder after voiding
  • Reflux can also lead to scarring up to the kidneys

Haematogenous route - how the bacteria get to the kidneys

  • The kidney is frequently the site of abscesses in patients with Staph aureus bacteraemia or endocarditis or both.
    • Staph aureus doesn’t normally cause ascending UTI, so you need to think that they may have a deeper Staph infection elsewhere and the kidneys become seeded
    • Hence always do blood cultures if you see Staph aureus in the urine
  • It appears that in humans, infection of the kidney with G- bacilli rarely occurs by the haematogenous route.
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75
Q

Lower UTI v upper UTI symptoms

A

Lower UTI
Result from bacteria producing irritation of urethral and vesical mucosa
* Painful urinary
* Small amounts of turbid urine
* Suprapubic heaviness or pain
* Occasionally, the urine is grossly bloody or shows a bloody tinge at the end - may make you suspicious of other pathology like Ca in older patients.
* No fever!!!

Upper UTI

  • Fever!!! (sometimes with rigors: G- infection in particular)
  • Flank pain
  • Frequently lower tract symptoms (e.g. frequency, urgency, and dysuria)
  • At times, the LT symptoms antedate the appearance of fever and upper tract symptoms by 1 or 2 days.
  • The symptoms described, although classic may vary greatly.
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76
Q

HPA guidance re UTI investigations (when do we need to investigate and when do we need to treat?)

A
  • If a patient has >=3 symptoms than you can treat without the need for a dipstick
    • Dysuria: urgency, frequency, polyuria, suprapubic tenders, haematuria
  • Consider a sexually transmitted infection as a differential for UTI.
  • Nitrites are a by-product of coliform metabolism (E.coli) - very suggestive of E.coli
    • Positie nitrite very suggest of UTI
  • Leucocytes could be present for other reason e.g. TB, Abx therapy.
  • Asymptomatic bacteriuria treated in pregnancy because it is associated with pyelonephritis and premature delivery!!!!!!.
  • Bacteria can form biofilm on catheters, so don’t just send urine from a catheterised patient as it will often be positive. Only send if the patient is symptomatic.
  • Failed treatment: may have resistant organisms.
    • Community multi-resistance E.coli - requires culture to determine sensitivity and appropriate treatment
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77
Q

Interpreting urine culture results - LUTS symptoms with white cell but no bacterial growth? (3 reasons to explain)

A
  • Sterile pyuria
    • May have chlamydia trachoma’s infection
    • TB - require special culture
    • Or if the pt is already on antibiotics - false negative

More notes on Sterile pyuria

  • In medicine, pyuria is the condition of urine containing white blood cells or pus. Defined as the presence of 6-10 or more neutrophils per high power field of unspun, voided mid-stream urine.
  • It can be a sign of a bacterial urinary tract infection. Pyuria may be present in the septic patient, or in an older patient with pneumonia.
  • Sterile pyuria is urine which contains white blood cells while appearing sterile by standard culturing techniques.
  • It is often caused by sexually transmitted infections, such as gonorrhea, or viruses which will not grow in bacterial cultures. Sterile pyuria is listed as a side effect from some medications such as paracetamol (acetaminophen).
  • Its occurrence is also associated with certain disease processes, such as Kawasaki Disease and genitourinary tuberculosis.
  • However, there are many known causes, including systemic or infectious disease, structural and physiological reasons, intrinsic kidney pathology, or drugs.
  • Reasons:
    • Prior treatment with abx
    • Calculi
  • Catheterisation
  • Bladder neoplasm
  • TB: doesn’t grow well in a normal culture
  • Sexually transmitted disease.
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78
Q

Interpreting urine culture results - lots of epithelial cells?

A
  • Epithelial cells
    • Urethra is lined with squamous epithelial cells - if there is a lot of epithelial cells means the culture is not a proper MSU
    • May grow urethra colonisation instead or true bladder infection
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79
Q

Empirical treatment of UTI

A
  • Community lower UTI - usually trimethoprim (1st line) but increasing resistance

Imperial guidelines
- it pt is symptomatic for UTI
Uncomplicated female - cefalexin 500 BD PO for 3/7 or nitrofuratonin for 7 days
PREGNANT female - cefalexin for 7 days or 2nd line co-amox for 7 days
Male (always considered complicated) - cefalexin for 7 days or cipro for 14 days

  • Cefalexin is used in hospital patients: high rate of trimethoprim resistance.

If pt is elderly with bacteriuria but asymptomatic, DO NOT ROUTINELY TREAT

  • Recommend aminoglycosides on their own for elderly patients as they will be less likely to get C. diff. (cephaloposins are one of the 4Cs of C.diff)
    • Don’t treat the lab result, treat the patient.
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80
Q

Empirical treatment for upper UTI symptoms

A
  • Upper UTI symptoms - e.g. fever, use co-amoxiclav
81
Q

Fungal UTI how to treat?

A
  • Most candida UTIs occur in patients with indwelling catheters.
  • Removal of the catheter may result in cure.
  • Oral fluconazole is not more effective than no therapy.
  • There is no demonstrated benefit in the treatment of asymptomatic infection, and therefore therapy is not recommended.
  • Exceptions include renal transplant patients and patients who are to undergo elective urinary tract surgery.

Candida UTI/infection can also occur after abx for bacterial UTI
* Antibacterials have destroyed normal flora, resulting in thrush.

82
Q

Pyelonephritis

A
  • Infection of the kidney
  • Commonly associated with sepsis and septicaemia
  • Requires more aggressive treatment
  • Tx with broad-spectrum antibiotics.
    • Co-amoxiclav +/- gentamicin (especially if concerns about resistance)
    • Cipro not used any more because risk of C.diff and resistance
  • Imaging for recurrent pyelonephritis
    • Calculi
    • Structural cause
83
Q

Complications of pyelonephritis

A
  • Perinephric abscess
  • Chronic pyelonephritis
    • Scarring
    • Chronic renal impairment - long term sequelae (normal UTI don’t cause this)
  • Septic shock
  • Acute papillary necrosis (rare)
84
Q

23 year old male (completely healthy and normal immune system) in close contact of a person with smear positive pulmonary TB (shedding active TB). What is his lifetime risk of developing active TB?

A

10% risk of developing active TB

85
Q

Diagnosing TB what is the gold standard and what modalities of evidence are preferred

A
  • Culture: (Lowenstein-Jensen medium gold standard)
  1. Microbiology (strongest evidence and preferred but sometimes difficult to get)
  2. Radiology (CXR)
  3. Histology (from biopsies showing caseating granulomas with Langhan giant cells)
  4. Epidemiology

Diagnosis of TB is not straightforward. Put together the various possible evidences

86
Q

What is the role of NAAT (rapid nucleic acid antigen testing) in TB?

A
  • Rapid diagnoses of smear +ve (smear here means stain)

* Detects drug resistance mutations

87
Q

What does a positive tuberculin skin test mean?

A

Skin induration >10mm = positive

  • Tells you only about exposure not active disease
  • and hence not used to diagnose active disease
  • Cross-reacts with BCG
  • Delayed type hypersensitivity reaction
88
Q

What kind of hypersensitivity reaction is tuberculin skin test?

A
  • Delayed type hypersensitivity reaction
89
Q

Describe Interferon gamma release assays (IGRAs) for TB

A
  • Detection of antigen-specific IFN-gamma production
  • No cross-reaction with BCG
  • Cannot distinguish latent and active TB
90
Q

Who gets primary TB?

A

Usually children, elderly, HIV
Because of impaired immune system
Healthy individuals will be exposed to infectious TB and get latent TB or not get TB at all if infectious dose is too low

91
Q

How does primary TB present?

A

Asymptomatic usually

In immunoimpaired e.g children, HIV, elderly,
May present with Ghon focus in the mid and lower zones
The TB bacteria gets taken up by macrophage and brogue to local LN (Ghon complex)

In rare cases, (in order of increasing immune impairment), primary TB can present as

  • Lymph node (Ghon complex)
  • Localised extra pulmonary e.g. TB terminal ileitis in children because they can’t really cough so they swallow the bacteria
  • pulmonary localised
  • pulmonary widespread - Ghon focus ulcerates into bronchus causing pneumonia, cavitation, bronchiectasis, consolidation and lung collapse
  • meningeal +/- tuberculoma - TB meningits
  • military TB (Rich foci) caused by haematological spread hence TB is scattered throughout the lung as they were brought there by the vascular system)
92
Q

Gold standard diagnosis for TB

A

Culture in Lowenstein-Jensen media

93
Q

What is post-primary TB + PC

A

The most common form of TB seen in the UK
due to reactivation of latent TB as immune system declines
- old age
- HIV
- malnutrition
- chronic alcohol

PC: Cough, haemopytsis, weight loss, malaise, South Asian/ Sub-saharan africa

Classically upper lung fibrosis +/- caseating granulomas

94
Q

1st line treatment for pulmonary TB + duration. What is it is TB meningitis?

A

Rifampicin, isoniazid, pyrazinamide, ethambutol
All 4 for 2/12 then just RIF and INA for 4/12

For TB meningits, increase the second half to therapy to RIF and INA for 8-10/12

Also Vit D supplement +/- surgery

95
Q

Treatment for latent TB?

A

6/12 Isoniazid

Isoniazid is also prophylaxis for TB

96
Q

What is drug resistance TB MDRTB and XDRTB? + what to do?

A
  • Multi-drug resistant TB (MDR)
    • Resistant to rifampicin & isoniazid
    • Typically 18-24 months treatment
    • Recent May 2016 - study by MSF and WHO recommends now to do a short segment of 9-12 months but with stronger drugs at the start
  • Extremely drug-resistant TB (XDR)
    • resistant to rifampicin + isoniazid + fluoroquinolones & at least 1 injectable
      e. g. of injectable = Capreomycin, kanamycin, amikacin
  • 4/5 drug regimen, longer duration
    • Quinolones, aminoglycosides, PAS, cycloserine, ethionamide,
97
Q

2nd line therapy drugs to TB?

A
  • Second line medications
    • Quinolones (Moxifloxacin)
    • Injectables
      • Capreomycin, kanamycin, amikacin
    • Ethionamide/prothionamide
    • Cycloserine
    • PAS
    • Linezolid
    • Clofazamine
98
Q

Spinal TB presentation + inx + tx

A

Also known as pott’s disease

  • Fever, sweats, wt loss, Back pain -Haematogenous spread initial discitis Vertebral destruction + collapse ± Anterior extension (causing iliopsoas abscess)
  • Ix – MRI/CT ± Biopsy/Aspirate
  • Treatment – 12/12 anti-TB
99
Q

Examples of extra pulmonary TB

A
  • Lymphadenitis
    • AKA scrofula
      • Mycobacterial cervical lymphadenitis, also known as scrofula or King’s evil, refers to a lymphadenitis of the cervical lymph nodes associated with tuberculosis as well as non-tuberculous (atypical) mycobacteria.
    • Cervical LNs most commonly
    • Abscesses & sinuses
  • Gastrointestinal
    • This is the dominant form in children
    • Swallowing of tubercles because they don’t tend to cough
    • Large lymph nodes can cause stricturing and look like Crohn’s disease
    • Can also cause a TB terminal ileitis.
  • Peritoneal
    • Ascitic or adhesive
  • Genitourinary
    • Slow progression to renal disease
    • Subsequent spreading to lower urinary tract
  • Bone and joint
    • Haematogenous spread
    • Spinal TB most common → Pott’s disease.
    • Typically thoracic (from lungs)
    • Destroyed vertebrae and become hunchbacked
  • Miliary TB
    • Millet seeds on CXR (looks like scattered oat seeds) because it came from blood not the airways
    • Progressive disseminated haematogenous TB
    • Increasing due to HIV
  • Tuberculous meningitis
    • Commonest form of meningitis in sub-Saharan Africa.
    • Can be indolent for a period of time before presenting to the hospital with more severe symptoms to reduced GCS and seizures
100
Q

TB meningitis - presentation/inx/tx

A 
Subacute presentation 
Weight loss, fever, night-sweats 
Headache, neck- stiffness
Personality change, ↓ GCS
Focal neurological deficit
Diagnosis : CT – tuberculomata, LP – Lymphocytic
Rx – >12/12 anti-TB + steroids
101
Q

Challenges in TB and HIV - diagnosis

A
  • Clinical history
    • Less likely to be classical
    • Symptoms and signs often absent in population with low CD4 count (data from a number of cohorts starting HAART in Africa)
  • Chest X-ray
    • Likely normal x-ray because they don’t have the immune response to give you the classic x-ray appearance
    • More likely extrapulmonary
  • Smear microscopy & culture
    • Less sensitive
  • Tuberculin skin test
    • More likely to be negative
  • Sensitivity of IGRAs for active tuberculosis (Goletti et al PloS One 2008)
    • Quantiferon Gold
      • 78.1% (95% CI 70.7, 84.3)
    • T SPOT
      • 85.1% (95% CI 79.2, 89.9)
  • Timing of treatment initiation
  • Drug interactions
  • Overlapping toxicity
  • Duration of treatment – adherence
  • Health care resources
102
Q

TB vaccination +?HIV pts

A
  • Bacille Calmette-Guerin (BCG): live attenuated M. bovid strain
    Efficacy 0-80% – Bad for pulmonary TB. Good for leprosy, TB meningitis, disseminated TB.
    • Given to babies in high prevalence communities only (since 2005) - If >10 cases per 100,000 children may be offered the BCG vaccine.
    • Primarily protects against miliary TB and TB meningitis in the early years of life.
      • 70-80% effectiveness in preventing severe childhood TB
    • But little evidence in adults
      • BCG is a pretty terrible vaccine.
      • Protection wanes

Contraindicated in HIV pts
-HIV –ve latent TB active TB 5-10% lifetime risk
-HIV +ve latent TB active TB 5-10% yearly risk
- Be aware of immune reconstitution inflammatory syndrome (IRIS) in HIV
patients – development of symptoms after HIV tx started

103
Q
  • If someone has a ______or ___ deficiency then they can progress to active infection quite rapidly.
A
  • If someone has a IFN-gamma or IL-12 deficiency then they can progress to active infection quite rapidly.
104
Q
  • M. bovis
A

Example of tuberculous TB
Closely related to TB

  • Bovis is more common with contaminated milk products, it is intrinsically resistant to pyrazinamide and is used in the TB vaccine (BCG)
105
Q

Which of these viruses are routinely monitored in blood post BMT?

A
  • CMV and EBV

* CMV > EBV

106
Q

3 Different routes of infections in a transplant patient?

A

Viruses acquired from graft
* Hepatitis B, CMV

Viral reactivation from the host

  • Hep B/ Hep C
  • CMV and EBV common reactivation problems hence routinely monitored

Novel infection from infected individual
* Measles, parvovirus, VZV

107
Q

What we can do about opportunistic viral infections in post-transplant pt?

A

*Pre-transplant (prevent viruses from host/graft)
Serostatus of donor, pre-transplant pt serology and re-check serology when symptomatic post-transplant
Risk assessment pre-transplant

*post-transplant (prevent reactivation of latent viruses)
Monitoring
Prophylaxis e.g. HSV prophylaxis
Pre-emptive therapy

*Post-transplant (prevent novel infections) 
Isolation-barrier nursing 
Advice for family/contacts 
Post-exposure contacts 
Vaccinating contacts 
Control diet
108
Q

Symptomatic screening - Viral diagnostics in a post-transplant pt. What is usually used to diagnose infection?

A
  • Serology is not always reliable in transplant pts
  • Hence molecular testing by PCR is preferred
  • Also the list of organisms testing for is wider than a normal pt
109
Q

Name all 8 Herpes viruses and their sites of latent location

A

all alpha stay in nerves
* HSV1, HSV2 and VZV = sensory nerve ganglion

all beta herpes stay in lymphocytes

* CMV = B lymphocytes
* HHV6A and HHV6B = T lymphocytes and epithelial cells.
  • all gama herpes stay in epithelial cells
  • EBV = leucocytes and epithelial cells
  • HHV8 = epithelial cells.
  • HHV 1& 2 - HSV 1&2
  • HHV 3 - VZV
  • HHV 4 - EBV
  • HHV 5 - CMV
  • HHV 6/7 → Roseola infantosum
  • HHV8 → Kaposi sarcoma
110
Q

what is herpes latent infection

A
  • The virus establishes a latent infection that persists for the life of the host.
  • In the latent state only a small subset of the viral genes are expressed.
  • Reactivation with expression of viral proteins and production of new virus particles may occur at intervals to produce recurrent infections.
  • Leads to destruction of the host cells
111
Q

Herpes simplex virus (HSV) and the immunocompromised

  1. mechanism of infection specifically in transplant setting
  2. clinical presentation
  3. Treatment
A
  1. mechanism of infection specifically in transplant setting
    * Usual mechanism: viral reactivation in patients tested HSV IgG positive pre-transplant
    * Reactivation is common in the first month post-Tx
  2. clinical presentation
    * Most commonly:
    • Cold sores, stomatitis, mouth ulcers
    • Recurrent genital disease (HIV and adult transplant)
      * But can also get more serious complications :
    • Cutaneous dissemination and visceral involvement: oesophagitis, hepatitis, viraemia
  3. Treatment (same as VZV)
    * Treatment
    • Acyclovir or valaciclovir
      * Acyclovir is used as prophylaxis until CD4 count increases above a certain threshold
    • Foscarnet
    • Ganciclovir sensitive also
112
Q

Varicella-zoster virus infection in the immunocompromised

  1. mechanism of infection specifically in transplant setting
  2. clinical presentation
  3. Treatment
A
  1. mechanism of infection specifically in transplant setting
    * In the transplant setting:
    • Varicella (primary infection) - due to novel infection from third party
      • may have complications - not just simple chicken pox
    • Or Shingles → From reactivation of endogenous virus (latent in dorsal root ganglion) in patients who are VZV IgG positive pre-transplant
      • Late complication: >100 days post-BMT
  2. clinical presentation
    * Primary varicella infection → Carries an Increased risk of complications:
    • Secondary infection of rash
      • Can be impetigenous (staph usually) or herpetic (HSV)
    • Bullous or haemorrhagic skin lesions, purpura fulminans
      • Purpura fulminant in neonates (also known as “Purpura gangrenosa”) is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation.
    • Visceral involvement:
      • Pneumonitis and hepatitis+++
  3. clinical presentation of shingles
    * Shingles: Common late complication of transplant
    • 3 patterns:
      1. Dermatomal skin eruptions
      2. Varicella-like skin lesions with no dermatomal distribution (“atypical generalised zoster”): high risk of visceral involvement → multi-dermatomal or disseminated (high mortality)
      • Acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN)
      • VZV vasculopathy involvement in brain
        3. VZV reactivation without skin lesions
    • May be early sign of HIV infection in patient (indication for HIV testing in young person)
  4. Treatment
    * VZV prevention
    • Acyclovir at prophylactic dose provides some protection
      • Started pre transplant
      • Some HIV patients are on prophylaxis for years
    • Post-exposure prophylaxis of severe varicella:
      • Varicella zoster immunoglobulin (VZIG)
      • Within 10 days of a significant contact with a case of chickenpox (airborne) or shingles (direct contact)
        • VZV treatment (same as HSV)
    • Acyclovir or valaciclovir
    • Foscarnet
    • Ganciclovir sensitive also
113
Q

Mentimeter: Liver transplant pt presents with pain on swallowing. Which virus might be implicated?

A

HSV - mouth ulcers

114
Q

HSV and VZV treatment, drugs most commonly used

A
  • Aciclovir
    • Nucleoside analogue
    • ACV triphosphate is a potent inhibitor of HSV-encoded DNA polymerase
    • Oral or IV
  • Valaciclovir (valine ester prodrug of ACV)
    • Better bioavailability
  • Foscarnet sensitive
  • Ganciclovir sensitive
  • Both predominantly active against HSV, and to a letter extent VZV
  • Risk of resistance
115
Q

Cytomegalovirus (CMV) infection in immunocompromised

  1. mechanism of infection specifically in transplant setting
  2. clinical presentation
  3. Investigation/diagnosis
  4. Treatment
A
  • Site of latency: B lymphocytes
  1. mechanism of infection specifically in transplant setting
    * 3 sources of CMV infection after transplant
    1. Exogenous infection (primary CMV infection) e.g. from graft, blood products, persons excreting virus
    2. Endogenous reactivation (very common and hence routinely screened)
      • Solid organ transplant: D+/R- carries the greatest risk of reactivation (D+/R- means donor recipient mismatch, with the donor being positive for CMV)
      • BMT: adoptive immunity D-/R+ carries the greatest risk of reactivation.
    3. Exogenous reinfection
  2. clinical presentation (key are in CAPS)
    CMV infection, disease manifestations
    * FEVER
    * BONE MARROW SUPPRESSION
    * Interstitial PNEUMONITIS
    * Delayed engraftment, graft failure
    * HEPATITIS
    * Oesophagitis, gastritis, enterocolitis
    * Immunosuppression
    * CMV RETINITIS (HIV patients when CD4 <50cells/mm3)
    • Retinitis can also be caused by HSV and VZV
      * Left: Chest radiograph showing multifocal patchy pneumonia due to CMV infection
      * Right: CMV retinitis
  3. Investigation/diagnosis
    CMV infection diagnosis
    * PCR
    • EDTA blood (viral load), biopsy, CSF, vitreous fluid
    • However even the detection of viraemia does not guarantee that CMV is the cause of the clinical syndrome
    • Ideally samples should be collected from target organs
      * Histopathology
    • Characteristic Owl’s eye inclusions
    • Provides a specific diagnosis
    • But known to be insensitive
      * Tissue immunofluorescence
    • Some biopsy samples (lung, liver) may contain cells infected with CMV which can be visualized with antisera against CMV antigens.
  4. Treatment
    Prevention:
    * BMT: CMV viral load twice weekly, treat if virus reactive and until suppressed
    * Solid organ: valganciclovir prophylaxis for 100 days

CMV treatment

  • Ganciclovir (IV): most commonly used:
    • Can also be applied to the eye via an impant that gives long lasting ganciclovir to the eye for CMV retinitis
  • Valganciclovir: oral prodrug of ganciclovir
  • Foscarnet (IV)
  • Cidofovir (nephrotoxicity)

For CMV pneumonitis:
* CMV hyperimmunoglobulin (IVIG) + another drug for pneumonitis

New agents in Phase 3 for CMV on the horizon

  • Latermovir
  • Maribavir
  • Brincidofovir
  • Fomiversin
116
Q

Epstein-Barr virus in immunocompromised v normal host

  1. mechanism of infection specifically in transplant setting
  2. clinical presentation
  3. Investigation/diagnosis
  4. Treatment
A
  • EBV infection in the normal host:
    • Acute: infectious mononucleosis. EBV mainly infects B cells
      • Febrile illness with lymphadenopathy and moderate hepatitis.
    • Chronic: lifelong low-grade replication in B lymphocytes with polyclonal activation, kept in check by the cellular immune system (particularly T cell)
  1. mechanism of infection specifically in transplant setting (reactivation)
    In post-transplant -→ unique POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE
    * illustration of immunosurveillance breakdown
    * Latently infected B cells – polyclonal activation
    * Predisposes to lymphoma
  2. clinical presentation
    * Other conditions caused by EBV
    • Oral hairy leukoplakia in HIV infected patients (seen below)
    • Lymphomas (primary brain lymphoma, Burkitt’s etc.)
  3. Investigation/diagnosis
    * Suspicion on rising EBV viral load (> 105 c/ml) and CT scan
    * Confirmation with biopsy of lymph nodes
  4. Treatment
    * Management:
    • Reduce immunosuppression (regression in < 50%)
    • Anti-CD20 monoclonal Ab therapy (B cell marker)
      • Give “rituximab” if EVB viral loads goes up - way of preemptive treatment
117
Q

Human herpesvirus 8 in immunocompromised

  1. mechanism of infection in this particular group of pt
  2. clinical presentation
  3. Investigation/diagnosis
  4. Treatment
A
  1. mechanism of infection in this particular group of pt
    * Particular problem in HIV infected patients (AIDS-defining disease)
    * Pre-HIV epidemic
    indolent tumour of
    elderly men in Mediterranean
  2. clinical presentation
    * Kaposi sarcoma!!!!
    * Primary effusion lymphoma (body-cavity associated) (PEL)
    * Multicentric Cattleman’s disease

KAPOSI SARCOMA

  • Clinical presentation: bronwish/purplish vascular lesion, can be cutaneous or visceral
  • Involves the lymphatic endothelium
  1. Investigation/diagnosis
    Definite diagnosis can only be made by biopsy
  2. Treatment
    * Treatment: radiotherapy, surgical, IFN-A, chemotherapy.
118
Q

For interest/reading: HHV8 causes PEL (primary effusion lymphoma)

A
  • Primary effusion lymphoma (body-cavity associated) (PEL)
    • Primary effusion lymphoma (PEL) is a B-cell lymphoma, presenting with a malignant effusion without a tumor mass.
    • PEL most commonly arises in patients with underlying immunodeficiency, such as AIDS.
    • PEL is caused by Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8).
    • In most cases, the lymphoma cells are also infected with Epstein Barr virus (EBV)
119
Q

For interest/reading: HHV8 causes Multicentric Castleman’s disease

A
  • Castleman disease, also known as giant or angiofollicular lymph node hyperplasia, lymphoid hamartoma, angiofollicular lymph node hyperplasia, is a group of uncommon lymphoproliferative disorders that share common lymph node histological features that may be localized to a single lymph node (unicentric) or occur systemically (multicentric). It is named after Benjamin Castleman.
  • Multicentric Castleman disease (MCD) involves hyperactivation of the immune system, excessive release of proinflammatory chemicals (cytokines), proliferation of immune cells (B cells and T cells), and multiple organ system dysfunction.
  • Castleman disease must be distinguished from other disorders that can demonstrate “Castleman-like” lymph node features, including reactive lymph node hyperplasia, autoimmune disorders, and malignancies.
  • While not officially considered a cancer, the overgrowth of lymphocytes with this disease is similar to lymphoma and more research is needed to search for small populations of neoplastic cells.
  • Lymph node abnormalities and organ dysfunction in Castleman disease are caused by hypersecretion of cytokines.
  • IL-6 is the most commonly elevated cytokine, but some patients may have normal IL-6 levels and present with non-iron-deficient microcytic anemia.
120
Q

JC virus infection: Progressive multifocal leukoencephalopathy

  1. mechanism of infection
  2. clinical presentation
  3. Investigation/diagnosis
  4. Treatment
A
  • JC virus is a polyomavirus
  • Prior to the introduction of effective antiretroviral therapy, PML occurred in 5% of patients with AIDS with a high mortality, the incidence has now drastically declined
  • PML can be seen in other types of immunosuppressed hosts:
    • I.e. patients on high dose steroids, patients on humanised monoclonal antibodies such as Natalizumab (for treatment of R+R multiple sclerosis)
  1. clinical presentation
    * Cognitive disturbance
    * Personality change
    * Motor deficits
    * Other focal neurological signs
    * Main feature if demyelination of white matter with neurological deficits corresponding to area(s) of the brain affected
  2. Investigation/diagnosis
    * Diagnosis: MRI and PCR on CSF
121
Q

BK virus in immunocompromised

A
  • postBMT: BK cystitis

* pre-renal transplant: nephrophathy

122
Q

Adenovirus in immunocompromised

  1. mechanism of infection in transplant patients
  2. clinical presentation
  3. Investigation/diagnosis
  4. Treatment
A
  • Particular problem post-BMT (paeds!)
    • Less common than CMV disease, but still a problem in BMT
  1. mechanism of infection in transplant patients
    * Exogenous infection or reactivation of persistent endogenous infection.
  2. clinical presentation
    * Fever
    * Pneumonitis
    * Encephalitis
    * Colitis
    * Prognosis: High mortality with disseminated infection (>2 organ systems)
  3. Investigation/diagnosis
    - Weekly blood monitoring for paediatrics - Symptomatic screening in adults: urine,
    respiratory & stool
    - Staging for disseminated dx to include
    blood if any above +ve
  4. Treatment
    * Commence pre-emptive tx (While pt is asymptomatic) if viral load increases/reaches critical load
    • High risk:>100counts/ml
    • Intermediate risk: >1,000 counts/ml
    • Low risk: CD3 <25/μl or <300/μl within 2/52 - >1,000 counts/ml; CD3 >25/μl & >300/μl within 2/52 - >10,000 counts/ml
      * Pre-emptive treatment
    • Cidofovir +hyperhydration + probenecid 3x/wk (min 2x)
    • Treatment until viral load <400 counts/ml
    • Taper immunosuppression if possible to allow patient to mount immune response
      * If treatment failure/symptomatic
    • Use adenovirus specific cytotoxic T cell infusion (immunotherapy)
    • If unable, just continue using cidofovir
123
Q

An HIV infected patient presents with skin lesions resembling Kaposi Sarcoma, what is the causative virus?

A

HHV8

124
Q
  • Which one of the following statements is not true?
    1. CMV pneumonitis has a poor prognosis
    2. CMV infection can cause bone marrow suppression
    3. Aciclovir is the treatment of choice of CMV infection
      • Ganciclovir is the treatment of choice.
    4. CMV can be transmitted from the graft
    5. CMV is a herpes virus that establishes latency in B lymphocytes
A
  1. Aciclovir is the treatment of choice of CMV infection

* Ganciclovir is the treatment of choice.

125
Q
  • A patient who received a stem cell transplant 2 weeks ago presents with mouth ulcers. Which of the following viral PCRs would you request on the mouth swab?
  1. Enterovirus PCR
  2. Adenovirus PCR
  3. HSV PCR
  4. HHV6 PCR
  5. HHV8 PCR
A
  1. HSV PCR
  2. Enterovirus PCR

HSV>enterovirus

126
Q
  • Which virus causes progressive multifocal leukoencephalopathy?
A
  • JC virus
127
Q
  • Which of the following viruses are associated with lymphoma
    1. CMV
    2. Adenovirus
    3. HHV8
    4. JC
    5. EBV
A
  1. HHV8: PEL

5. EBV: lymphoma

128
Q

Respiratory viruses in the immunocompromised + e.g.s

  1. mechanism of infection in transplant patients
  2. clinical presentation
  3. Investigation/diagnosis
  4. Treatment
A
  • Increased risk of complications (pneumonitis) and high mortality associated particularly with:
    • Influenza A and B
    • Parainfluenza 1, 2, 3 and 4
    • Respiratory Syncytial Virus (RSV) infection
    • Adenovirus
    • Novel coronavirus: MERS coronavirus
  1. mechanism of infection in transplant patients
    * Mechanism: novel infection from other infected people
  2. clinical presentation
    Respiratory
  3. Investigation/diagnosis
    * Specimens: Naso-pharynx aspirates (paeds), bronchio alveolar lavages, nose and throat swabs
    * Investigations:
    • Multiplex PCR is the method of choice:
      • Respiratory Syncitial Virus,
      • Human metapneumovirus,
      • Influenzae A and B
      • Parainfluenzae 1, 2, 3 , 4
      • Adenovirus, Rhinovirus…
    • Solid phase EIA for: RSV and flu
    • Direct Immunofluorescence and cell culture (no longer in use in most laboratories)
  4. Treatment
    * Influenza A and B
    • Oseltamivir (oral drug) for 5 days
      Prevention of respiratory virus infections
      * Prevention of influenza:
    • Life-long seasonal influenza vaccination of organ/BMT recipients
      * Influenza vaccination for close contacts
    • Oseltamivir prophylaxis if significant contact with case of influenza
      * Infection control!
    • Handwashing, protective clothing, limit visitors
    • Isolate immunocompromised patients (BMT)
    • Cohort nursing
129
Q

Human parvovirus B19 in immunocompromised

  1. . clinical presentation
  2. Investigation/diagnosis
  3. Treatment
A
  • Cause of chronic anaemia in the immunocompromised
  • Diagnosis:
    • Serology (IgM) not useful in the immunocompromised
    • PCR on blood
  • Treatment: Human normal immunoglobulin. May require blood transfusion
130
Q

HBV serology interpretation

  • HBsAg
  • HBcAg
  • HBsAb

what about HBeAg??

A
  • HBsAg (surface antigen) is present 1-6 months after exposure (during acute episode). But if this persist >6 months = pt is carrier
  • HBeAg (e antigen) is present 1-3 months after acute illness and implies high infectivity
    • You don’t get this from immunisation. This person had Hep B in the past and is now immune
    • Immunisation only gets surface antigen only
  • HBcAb (anti-HBc) imply past infection
  • HBsAb (anti-HBs) only imply vaccination

Current active infection

  • HBsAg +
  • HBcAb +
  • HBsAb -

Past infection

  • HBsAg -
  • HBcAb +
  • HBsAb +

Vaccinated

  • HBsAg -
  • HBcAb -
  • HBsAb +

The core protein is the major component of the nucleocapsid. HBeAg may be generated from the core protein by proteolytic cleavage.

131
Q

Hepatitis B in the immunocompromised + strategies for prevention

A
  • Two things can happen:
    • Carriers may have flare of disease.
    • Those who have had past infection (ie core Ab+/surface antigen-) may revert to positive surface antigen
  • The risk of reactivation is particularly important with patients on B-cell depleting therapies (i.e. Rituximab)
  • Prevention:
    • Nucleoside/nucleotide analogues (eg lamivudine, tenofovir, entecavir)
    • Hepatitis B immunoglobulin in liver transplant
132
Q

Hepatitis E virus

  • How is it transmitted
  • how is infection in immunocompromised different from healthy?
A

Hepatitis E virus (clinically similar to HepA)

  • HEV is endemic in the UK (and in much of Europe)
  • Has now become the major cause of enterically transmitted viral hepatitis
  • Modes of transmission of indigenous HEV in developed countries:
    • Mainly through the consumption of undercooked meat such as pork (the virus has also been found in wild boar, deer and rabbits)
  • Other modes of transmission:
    • Through blood transfusion, although uncommon
      • (In a recent study, a prevalence of HEV viraemia of 1:2848 blood donations (0.04%) was found in Southeast England, with a transmission rate of 42%)
    • Possibly through organ donation
  • In the immunocompromised population
    • HEV can cause significant morbidity and can establish chronic infection
    • Treatment consists of a dose reduction of immunosuppressants where possible, and/or addition of ribavirin
  • In normal population
    • No carrier states
    • No chronicity
  • At present there is no recommendation for routine screening of blood, organ and tissue donors, however this may change in the future
133
Q

Virological investigation of transaminitis in post-transplant and other immunocompromised patients (7)

A
  • Should include the following basic screen (additional tests may be indicated):
    • Hepatitis A IgM
    • Hepatitis B surface antigen
    • Hepatitis C virus PCR
    • Hepatitis E virus PCR
    • CMV PCR and EBV PCR
    • Adenovirus PCR for paediatric patients
134
Q

Please examine the following hepatitis B serology results, which profile is consistent with past hepatitis B infection?

A. HBV sag (+), HBV core ab (+), HBV sab (-)
B. HBV sag (-), HBV core ab (-), HBV sab>100mIU/ml
C. HBV sag (-), HBV core ab (-), HBV sab (-)
D. HBV sag (-), HBV core ab (+), HBV sab of 15mIU/ml

(sag is surface antigen, sab is surface antibody)

A

A. HBV sag (+), HBV core ab (+), HBV sab (-)

135
Q

A patient who received a stem cell transplant recently has a transaminitis. What investigations would you request on blood?

A. EBV serology
B. Hepatitis B surface antigen
C. Hepatitis C PCR
D. Hepatitis E PCR
E. CMV serology
A

B. Hepatitis B surface antigen
C. Hepatitis C PCR
D. Hepatitis E PCR

136
Q

Influenza tropism - why can influenza only affect lungs?

A
  • The host cell receptor (sialic acid) the virus predominates the upper respiratory tract
  • The influenza virus can only get into the body through the mouth
  • Influenza virus requires activation by host cell proteases that are only expressed in the respiratory tract (Clara trypase)
  • The influenza virus envelope can only fuse with membranes of cells that secrete mucus
137
Q

How does influenza A infect a cell?

A

• Viral haemagglutinin (HA) is cleaved by host cell proteases only expressed in respiratory tract (e.g. human airway Clara tryptase)
• Cleaved HA then binds to sialic acid
receptors on cell surfaces
• Allows virus to infect host cells
• Replicates within cell (specifically the nucleus) for 6-8hrs then tries to
escape
• Neuraminidase (NA) is used to cleave sialic
acid to free the new viral particle
• Allows it to freely infect neighbouring cells

138
Q

What makes a pandemic

A
  • Novel antigenicity
  • Virus replicate efficiently in human airway such that the airway cell will be shed out and spread through the air to people around
  • Transmit efficiently between people

Whilst not killing the host
* Since 1997, a number of avian influexna viruses have infected humans, often with high case fatality but they have not led to pandemics because they do not transmit through the air between people

139
Q

Influenza pandemics viruses evolve into seasonal influenza viruses

A
  • Stage 1: Avian influenza is restricted in human
  • Stage 2: Partially adapted avian influent causes severe disease
  • Pandemic: Pandemic influenza
  • Stage 3: Seasonal influenza
    • Don’t kill host so that host can spread more viruses
140
Q

What is antigenic shift?

A

Reassortment - antigenic shift

  • Influenza virus - segmented genome
  • Two different viruses that enter the same cell and have their genes muddle up together also called antigenic shift
  • hence difference between severity of 1918 flu v later pandemics. 1918 (Spanish flu) is completely de novo mutation hence very severe and later one is reassortment = milder changes
141
Q

T/F: we do not use multiple anti-viral drugs together to treat influenza virus

A

TRUE

* Reason: because they target the exact same spot and hence given multiple will make it a competition

142
Q

Barriers for animal virus to infect humans?

A

Different environment presented for transmission info avian and human influenza

  • Avian - closed quarters
  • Humans - not so much, virus need to survive longer in environment,

Different host defence
* Humans -different defence mechanisms - cilia, mucus, acidity

143
Q

Barriers for animal virus to infect humans?

A

Different environment presented for transmission info avian and human influenza

  • Avian - closed quarters
  • Humans - not so much, virus need to survive longer in environment,

Different host defence
* Humans -different defence mechanisms - cilia, mucus, acidity

144
Q

Therapies for influenza

A

Amantadine (influenza A only)

  • Targets M2 ion chanel
  • Single amino acid mutation in M2 (S31N) renders virus resistant
  • Does not work against influenza B or pH2N2 or seasonal H3N2 (because all viruses now is resistant to this)

Neuraminidase inhibitiors and mode of administration:

  • Must be given within 48 hours of symptom onset to have significant impact
    • Tamiflu (oseltamivir) oral
    • Relenza (zanamiri) inhaled or iv formulation
    • Peramivir Iv
  • Drug resistant variants have emerged in immunocompromised (e.g. leukaemia patient). But they do seem to come with a fitness cost
145
Q

Describe the Two types of season flu vaccine

A 
Trivalent/quadrivalent inactivated virus vaccine:
1. Split or subunit- HA rich
2. Given to those at higher risk of
complications
3. Short term strain specific immunity
mediated by Ab to HA head
rivalent/quadrivalent live attenuated
virus vaccine:
1. Cold adapted virus limited to upper
respiratory tract
2. Given to children
3. Broader more cross reactive immunity
due to inducement of cellular response
146
Q
  • SBA: The influenza vaccine given to those at greatest risk of complications from flu in the UK is
A
  • A: A purified fraction containing HA and NA of an inactivated virus
147
Q
  • SBA: What new vaccination strategy has been instigated since the 2009 pandemic?
A
  • A: Children are to be vaccinated with live attenuated quadrivalent seasonal influenza vaccine

Not because they suffer the worst symptoms or risk to life but because they are the biggest spreaders

148
Q

Antigenic shift v drift

A

Antigenic Drift = Mutation occur to HA/NA to give new strains of the virus Antigenic Shift = Complete change of HA/NA
o Can only occur with influenza A
o There is trading of RNA segments between human and animal strains

149
Q
  • A patient with chronic hepatitis B presents with a mass in the liver. Very high alfa-veto protein
A
  • Hepatocellular carcinoma
150
Q
  • What diagnosis is supported by: anti-HCV Ab negative, HCV RNA positive?
A
  • Acute hepatitis C infection
151
Q
  • What diagnosis is supported by: anti-HAV IgG negative, IgM positive?
A
  • Acute hepatitis A infection or recent vaccination
152
Q
  • What diagnosis is supported by: HBsAg positive, anti-HBc IgM positive, anti-HBc IgG negative
A
  • Acute hepatitis B infection
153
Q
  • What diagnosis is supported by: HBsAg negative, anti-HBc IgG negative, anti- HBsAg >1000u/ml?
A
  • Successful vaccination
154
Q

Define congenital infections

A
  • Congenital infections may be vertically transmitted from mother to baby
  • Infection can occur at any time during pregnancy between 1st trimester & birth
155
Q

Toxoplasmosis

A
  • Comes from unwashed fruit and vegetables, and soil/cat faeces
  • It is a parasite
  • Rare for infected mothers to present with symptoms although some may develop flu-like illness. Treatment with spiramycin
  • The higher the gestation, the more likely for infection to be passed to baby. Fatal infection can be diagnosed with amniocentesis or cordocentesis.

60% are asymptomatic at birth
* May still go on to suffer long term sequelae - deafness, low IQ, microcephaly → cerebral palsy

40% symptomatic - Toxo causes watery, dumb small head with calcifications and large spleen&liver. Also chorioretinitis + jaundice

  • chorioretinitis
  • microcephaly
  • hydrocephalus
  • seizures
  • Jaundice
  • Intracranial calcifications
  • Hepatosplenomegaly
156
Q

Name the only congenital infection that causes cataracts?

A

Rubella

  • Other cases of congenital cataracts:
    • Chondrodysplasic syndrome
    • Down syndrome (trisomy 21)
    • Familial congenital cataracts
    • Galactoseamia (X-ref path chempath)
    • Pierre-Robin sequence/syndrome
    • Trisomy 13
157
Q

Congenital rubella syndrome

A

Occurs if rubella <20/40
The earlier the infection, the worse it is

<8/40

  • 20% go into spontaneous abortion
  • 90% will have defects at birth

8-12/40

  • cataracts - the only congenital infection to cause this
  • congenital glaucoma
  • congential heart disease
  • loss of hearing
  • pigmentary retinopathy - salt and pepper chorioretinitis v pizza topping in CMV
  • purpura, splenomegaly,
  • microcephaly, mental retardation, meningoencephalitis

13-18/40
* Only hearing defects and retinopathy

> 20/40
No effects

You can offer TOP is rubella <16/40 because it is so severe

158
Q

Measles in a child/adult

A

Transmission:
• Respiratory
• Conjuctiva

Incubation
• 7-18 days (typically 10)

Symptoms
• Prodrome 2-4 days: fever, malaise, congestion, conjuctivities, kopek’s spots!!!
• Rash classically starts behind ears and on forehead then spread !!!!

Complications
• Opportunistic bacterial infections -> ostitis media, pneumonia, bronchitis
• Encephalitis
SSPE

159
Q

Measles in pregnancy

A 
Rare in pregnant women in UK 
•	Fetal loss (miscarriage, IUD) 
•	Pre-term delivery 
•	Increased maternal morbidity 
•	No congenital abnormalities to fetus

In susceptible pregnant woman in contact with suspected/confirmed measles
• Give measles Ig
• Attenuates illness
No evidence that it prevents IUD or pre-term delivery

160
Q

Parvovirus B19 in a child + what’s the characteristic rash and what is worrying

A

Transmission:
• Respiratory
• Blood products

Incubation:
• 6-8 days
Symptoms:
• Asymptomatic
• Erythema infectiosum/ slapped cheek/ 5th disease
• Polyarthropathy
• Transient aplastic crisis !!!! worrying - also reason why in utero measles baby may need blood transfusion

Diagnosis
Serology and molecular tests

161
Q

Maternal measles infection - what are the consequences/management

A 
Maternal infection before 20/40 
•	Est 33% transplacental
•	9% risk of infection overall 
•	3% risk of hydrops fetalis 
•	<1% risk of fetal anomalies

Maternal infection after 20/40
No documented risk

Refer to fetal medicine for monitoring

Intraueterine transfusion improves fetal outcome

162
Q

Congenital zika syndrome

A 
Congenital Zika syndrome 
•	Severe microcephaly + skull deformity 
•	Decrease brain tissue, seizures 
•	Retinopathy, deafness 
•	Talipes (club foot) 
•	Hypertonia

Associated with travel to
• Caribbean/Central/South America
Antigua, Barbados, Grenada, Jamaica, St Lucia and Trinidad and Tobago

163
Q

Prevention and treatment for zika virus

A

Current advice regarding Zika:
• All travellers – bite avoidance
• Pregnant women – avoid travel to areas with current transmission
• Avoid conception for 2-6 months after travel (prolonged viral sheeding in semen)
• Testing only if symptomatic or abnormalities identified on antenatal USS for both pregnant women and non-pregnant people.

164
Q

What is zika virus

A

Transmission:
• Through mosquito vectors spreading between infected and non-infected individuals
• Pregnant women -> foetus
• Sex (virus persist in semen for 6 months)
• Blood transfusion

Symptoms:
• 80% of infections asymptomatic
• Headache, red eyes, fever, rash, joint pain, muscle pain

Also recently recognised as a cause of Guillain Barre syndrome

165
Q

Varicella infection in pregnancy, divided into early and late

A

Varicella in early pregnancy -> Congenital varicella syndrome
• Mother infected during early pregnancy
• VZV from mother spread to fetus (transplacental, ascending vaginal)
• 0.4% for maternal infection between 0-12/40
• 2% for maternal infection between 12-20/40
• Short latency due to poorly developed fetal cell-mediated immunity
Symptoms
• Skin scarring
• Limb hypoplasia
• Muscular atrophy
• Rudimentary digits
• Cortical atrophy
• Psychomoor retardation
• Choreoretinitis
Cataracts

Varicella in late pregnancy 3rd trimester/ around delivery -> Neonatal varicella
• Mother is infected from 7 days prior to delivery to 7 days post-partum
• Route of infection can be transplacental, ascending vaginal or result from direct contact with lesions during or after delivery
• Also contact with a person other than the mother with chickenpox or shingles during 1st day of life

Symptoms
• Severe disseminated haemorrhageic neonatal VZV -> purpura fulminans
30% case fatality in untreated cases

All infants exposed to chickenpox <7 days old and mother if VZV IgG negative = VZV Immunoglobulin

166
Q

Diagnosis for VZV is NOT SEROLOGY! unlike other viruses

A

Diagnosis:
• Clinical
• Vesicle fluid for VZV PCR, (electron microscopy)
NOT serology

167
Q

Neonatal herpes

A

Symptoms of neonatal herpes
• Appear 3 days – 6 weeks post delivery
• Lesion of skin, eye, mouth lasting 7-12 days
• Neurological symptoms +/- SEM 2-6 weeks
• Disseminated disease with/without vesicles frequently involving brain 4-11 days
• Mortality in untreated cases of disseminated disease exceeds 80%

Primary genital infection in 3rd trimester pose greatest risk of transmission to infant. • Casarean recommended if primary HSV in final 6 weeks of pregnancy

Recurrent outbreak
* Still able to transmit to infant but not too concerning as mother’s antibodies offer protection in postnatal period
Prolonged rupture of membranes and invasive fetal monitoring in labour should be avoided

Diagnosis:
• Neonatal swab – oral, rectal, mucosal, umbilical (make sure to burst the vesicles to swab fluid)
+/- EDTA bloods for HSV PCR

(taken from teaching firms at SMH on neonatal herpes)

  • Any children born with vesicular rash = check if it is herpes
    • Swab (must burst the vesicles to swab the serous fluid)
    • Treat early
    • Survivors will have permanent sequelae
  • Only way to check if it is primary infection or non-primary infection is via serology
    • If it is primary infection, IgG-ve (as not yet seroconverted)
    • If non-primary, IgG+ve
  • LOTS OF HSV IS ASYMPTOMATIC
  • Low risk babes (lesions in mother before pregnancy or resolved by 3rd trimester) = swab baby, observe 24-48 hours
  • If baby develops first symptoms in 6 weeks (primary infection) or mother has active symptoms at delivery = high risk, swab baby and treat
    • primary infection in mother + <4 hours PROM = medium risk
    • Primary infection into there + >4 hours PROM = high risk
    • HENCE ALWAYS ASK HOW LONG PROM!!!
  • What swabs on baby (if no lesions but risk)
    • Nose
    • Eye
    • Mouth
    • Anus
  • Requires 1 year prophylaxis in babies as HSV can reactivate
168
Q

Rubella infection

A 
Rash begins on face and spread caudally 
Headache 
low grade fever 
Forchheimer spot on soft palate 
lymphadenopathy
169
Q

Define Neonatal infections

A
  • Refers to infections in the 1st 6/52 of life
  • Higher incidence of infection this period than at other stage of life, even if preterm babies are excluded due to (risk factors)
    • Immature host defences
    • Exposure to bacteria and viruses from mother
    • Birth trauma
  • Can become ill rapidly & seriously → low threshold to culture and start antibiotics

Neonatal infections is separated according to early and late onset infection

  • Early onset = <48 hours
  • Late onset = >48 hours
170
Q

Differentiate between the organisms of early v late onset sepsis/neonatal infections

A

Early onset sepsis <48 hours

  • GBS
  • listeria
  • E. coli

Late onset sepsis >48 hours

  • All of early + “opportunistic” organisms
  • Enterococcus
  • Candida
  • Klebsiella
  • Enterobacter
  • Pseudomonas aeruginosa
  • Citrobacter koseri
171
Q

Risk factors for early onset sepsis <48 hours

A 
Maternal
PROM/prem. labour
Fever
Foetal distress
Meconium staining
Previous history
Baby
Birth asphyxia
Resp. distress
Low BP
Acidosis
Hypoglycaemia
Neutropenia
Rash
Hepatosplenomegaly
Jaundice
172
Q

Antibiotics for early v late onset sepsis

A

Early - * Antibiotics: benzylpenicllin & gentamicin

Late - flucoxacillin + gentamicin

Common
* Cefotaxmine + amoxicillin + gentamicin

173
Q
  • chocolate agar plate
A

Haemophilus influenzae: Gram -ve diplococcus that was prev. leading cause until vaccination programme started → chocolate agar plate

Also haemophilus ducreyi for chancord (single painful penile ulcer)

174
Q

45-75 y.o with rapidly progressive dementia with myoclonus, cortical blindness, akinetic mutism and LMN signs

A 
Sporadic CJD (80%) the most common kind 
No PRNP mutation
175
Q

30year old with pyschiatric symptoms e.g. anxiety, paranoia, hallucinations, later develops neurological symptoms (ataxia, myoclonus, peripheral sensory symptoms)

A

variant CJD (acquired) use to exposure to bovine spongiform encephalopathy

176
Q

Previous surgery. Progressive ataxia. Later dementia and myoclonus. Speed of progression depends on route of inoculation

A

Iatrogenic CJD

Due to exposure to human prions from prior surgery

177
Q

Name the 2 familial CJD

A

Gerstmann-Straussler-Scheinker syndrome - AD PRNP mutation

  • develops in 20-60 years old
  • survival for 5 years
  • dysarthria progressing to cerebellar ataxia ending with dementia

Fatal familial insomnia

  • Insomonia and paranoia progressing to hallucinations and weight loss
  • then mute period
  • death 1-18/12 after symptoms
178
Q

Q1. What is the commonest form of prion disease?

  • Kuru
  • Iatrogenic CJD
  • Gerstmann-Straussler-Sheinker syndrome
  • Variant CJD
  • Sporadic CJD
A
  • Sporadic CJD
179
Q

Q2. Which statement is NOT true of sporadic CJD?

  • Median survival time is <6 months
  • Tonsillar biopsy is diagnostic
  • EEG usually shows periodic complexes
  • Mean age of onset is 65 years old
  • CSF markers (S100, 14-3-3) of neuronal damage may be elevated
A
  • Tonsillar biopsy is diagnostic

Tonsillar biopsy is useful for vCJD not sCJD

180
Q

Describe variant CJD presentation

A

younger 30 year old with psych first than neurological
- mean survival 14/12 (better than sCJD which is 6/12 survival)
EEG in this case is non-specific (v periodic,triphasic EEG in sCJD)
CSF in this cause is not useful (sporadic CJD CSF look for 14-3-3 protein and S100 protein)

181
Q

Q4. Prion genetics: which is true?

  • The vast majority of cases of variant CJD have been found to be methionine homozygous (MM) at codon 129 of PRNP
  • Familial prion disease does not cause ataxia
  • In familial prion disease mutations are usually inherited recessively
  • Familial CJD is more rapidly progressive than sporadic CJD
A
  • The vast majority of cases of variant CJD have been found to be methionine homozygous (MM) at codon 129 of PRNP

ALL vCJD is 129 codon MM
Most cCJD is 129 codon MM

182
Q

Genetics polymorphism in CJD

A

Prion protein (PRNP) gene is found on chromosome 20.

Polymorphism codon 129 MM
methionine-methionine

183
Q

Prion protein in CJD v healthy

A

healthy prion protein

  • a-helical configuration
  • protease sensitivity

CJD/mutated prion protein

  • beta-sheet
  • protease/radiation resistance

Trigger for changes unclear in sporadic cases. Mutation known in familial cases

184
Q

Inheritance pattern of familia CJD

A

Autosomal dominant

185
Q

Clinical presentation of sCJD

A
  • Clinical presentation
    • Dementia, alongside the following:
    • Myoclonus – these are random sporadic jerks
    • Cortical blindness – the problem is in the occipital cortex
    • Akinetic mutism – they cannot speak
    • LMN signs

Usually 65 year old onset

186
Q

Chlamydia trachomatis

A

Gram-negative, obligated intracellular parasites
• Chlamydia A, B, C: infect conjunctiva causing trachoma
• Chlamydia D to K: genital chlamydia infection, ophthalmia neonatorum
• Chlamydia pneumoniae and psitacci: infect lungs causing pneumonia
• L1-L3: Lymphogranuloma venereum (LGV) cause rectal infection and proctitis

187
Q

Any infant with urti what organism?

A

RSV is the most common not influenza

188
Q

what organism most commonly causes exacerbation of asthma in children?

A

RSV

189
Q

Treatment of unwell child with pneumonia and parapneumonic effusion?

A

IV antitbiotics until afebrile for 2 days before changing to oral antibiotics

190
Q

PUO investigations (bloods)

A

FBC - high WCC (infection, lymphoma), high eosinophils (parasites)<
U&E (?HUS)
LFT (?hep/autoimmune)
ESR (autoimmune)

AT LEAST 3 blood cultures

HIV test
Thick and thin blood films for malaria

Autoantibodies e.g. ANA, anti-DNA,Ro,La, SM,ENA.RF

191
Q

Acute endocarditis

A

Staph aureus

192
Q

Subacute endocarditis

A

Strep viridians

193
Q

Endocarditis on prostehtic valve

A

Coagulate negative staph (staph epidermis) which forms biofilms

194
Q

IVDU endocarditis which valve

A

Tricuspid

Typically staph aureus

195
Q

Commonest cause of IE overall (combining both acute and subacute)

A

Strep viridans

196
Q

Abx for strep viridans endocarditis

A

benzylpen + gent

197
Q

Abx for staph aureus endocarditis

A

flucox

198
Q

MRSA endocarditis

A

vancomycin + gent

199
Q

Constipation, rose spots + leucopenia + bradycardia + replica in Peyer’s patches → intestinal perforation

A

Typhoid fever

Salmonella typhi

Sera's MBBS (12 decks)

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