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Pathology > Microbiology > Flashcards

Microbiology Flashcards

1
Q

what are the 2 classes of antibiotics that inhibit cell wall synthesis

A
  • beta-lactam antibiotics (penicillins, cephalosporins, carbapenems)
  • glycopeptides (vancomycin and teicoplanin)
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2
Q

is staph aureus gram positive or negative?

A

positive

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3
Q

is e coli gram positive or negative?

A

negative

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4
Q

beta-lactams mechanism of action

A
  • inactivate the enzymes that are involved in the terminal stages of cell wall synthesis (transpeptidases aka penicillin binding proteins) (beta lactam is a structural analogue of the enzyme substrate)
  • bactericidal
  • active against rapidly-dividing bactera
  • ineffective against bacteria that lack peptidoglycan cell walls (e.g., Mycoplasma, chlamydia)
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5
Q

name 2 beta-lactamase inhibitors

A
  • clavulanic acid
  • tazobactam
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6
Q

routes of pathogen entry into CNS

A
  • haematogenous (e.g., pneumococcus, meningococcus)
  • direct implantation (e.g., trauma)
  • local extension (e.g., from the ear)
  • PNS into CNS (e.g., rabies)
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7
Q

which route of entry of pathogens into CNS is the most common

A

haematogenous

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8
Q

causative agents of acute meningitis

A

neisseria meningitides
streptococcus pneumoniae
haemophilus influenzae

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9
Q

4 processes of septicaemia

A
  • capillary leak (albumin and other plasma proteins leads to hypovolaemia)
  • coagulopathy (leads to bleeding and thrombosis)
  • metabolic derangement (particularly acidosis)
  • myocardial failure (and multi organ failure)
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10
Q

most common organisms for aseptic meningitis

A

Coxsackie group B
echoviruses

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11
Q

most common organisms for encephalitis in adults

A

enteroviruses (Coxsackie A &B; echovirus; polio)
herpes simplex (1&2)

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12
Q

causative organisms for brain abscesses

A
  • streptococci (anaerobic and aerobic)
  • staphylococci
  • gram-negative organisms (mainly in neonates)
  • TB
  • fungi
  • parasites
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13
Q

complications of pyogenic vertebral osteomyelitis

A
  • permanent neurological deficits
  • significant spinal deformity
  • death
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14
Q

risk factors for pyogenic vertebral osteomyelitis

A
  • age
  • IV drug use
  • long term systemic steroids
  • diabetes mellitus
  • organ transplantation
  • malnutrition
  • cancer
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15
Q

CSF appearance in bacterial vs viral vs TB meningitis

A

Bacterial
- appearance: cloudy/turbid
- WBCs: elevated, primarily PMNs
- protein: elevated
- glucose: low
- opening pressure: elevated

Viral
- appearance: usually clear
- WBC: elevated, primarily lymphocytes
- protein: elevated
- glucose: normal
- opening pressure: normal or elevated

TB
- appearance: clear/slightly turbid
- WBC: elevated, mixed or lymphocytes primarily
- protein: elevated
- glucose: decreased
- opening pressure: elevated

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16
Q

classify Streptococcus pneumoniae

A

gram-positive
alpha-haemolytic
diplococcus

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17
Q

classify meningococcus

A

gram-negative
diplococcus
non-haemolytic

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18
Q

how to differentiate between haemolysis patterns in blood agar plates

A

beta-haemolysis: complete haemolysis. clear (transparent) zone surrounding the colonies (e.g., staph aureus, strep pyogenes)

alpha-haemolysis: partial haemolysis. colonies typically are surrounded by a green, opaque zone (e.g., strep pneumoniae).

gamma-haemolysis: no haemolysis occurs. no notable zones around the colonies (e.g., staphylococcus epidermis)

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19
Q

classify Listeria monocytogenes

A

gram-positive rods

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20
Q

stain used for TB

A

Ziehl-Neelsen

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21
Q

what stain do we use for cryptococcal meningitis? what do we expect to see?

A

India Ink stain
it appears like an orbit sort of structure - the yeast is in the middle and the capsule is around the outside

(+ high opening pressure when doing LP)

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22
Q

therapy for meningitis

A

ceftriaxone 2g IV bd
if >50 yrs or immunocompromised add
- amoxicillin 2g IV 4 hourly

if meningo-encephalitis:
- aciclovir 10mg/kg IV tds
- ceftriaxone 2g IV bd
- if 50 yrs or immunocompromised: add amoxicillin 2g IV 4 hourly

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23
Q

clinical features of HIV infection

A
  • anaemia
  • frequent nose bleeds
  • severe oral thrush
  • enlarged parotids
  • suppurative ear infection
  • progressive encephalopathy
  • failure to thrive
  • enlarged lymph nodes
  • enlarged liver and/or spleen
  • severe pneumonia/TB/LIP/pneumocystis carinii
  • clubbing
  • herpes zoster infection
  • severe nappy rash
  • recurrent/persistent diarrhoea
  • easy bruising
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24
Q

mechanisms of perinatal transmission of HIV

A
  • breastfeeding
  • in utero
  • intra partum (during labour)
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25
Q

classes of antiretrovirals that are currently used for children in Africa

A
  • non-nucleoside reverse transcriptase inhibitors
  • nucleoside analogues
  • nucleotide analogues
  • protease inhibitors
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26
Q

what is immune reconstitution inflammatory syndromes (IRIS)? (HIV)

A

revamping the immune system can lead to a severe inflammatory response which leads to deterioration in clinical state
- usually occurs in the first 6 months of treatment of HIV/AIDS patients

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27
Q

Pneumocystis jiroveci pneumonia: clinical presentation, investigations and management

A

most common opportunistic infection in AIDS

features:
- dyspnoea
- dry cough
- fever
- very few chest signs

pneumothorax is a common complication
extrapulmonary manifestations (rare):
- hepatosplenomegaly
- lymphadenopathy
- choroid lesions

investigations:
- CXR: typically shows bilateral interstitial pulmonary infiltrates but can present with other x-ray findings (e.g., lobar consolidation). may be normal
- exercise-induced desaturation
- bronchoalveolar lavage to show PCP (sputum often fails to show it)

management:
- co-trimoxazole
- IV pentamidine in severe cases

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28
Q

natural history of HIV infection

A
  • during the acute infection, you get a high viraemia which may be associated with symptoms (e.g., fever, rash)
  • seroconversion can also produce symptoms (e.g., fever, rash)
  • eventually, the viral load wtill fall and your CD4 count will recover
  • then you will be asymptomatic, which can last for years
  • eventually, the viral load will start to rise and the CD4 count will fall
  • you become immunocompromised and will be at risk of AIDS-defining conditions such as PJP
  • CD4+ count is a major determinant of immune damage and predicts short term outlook
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29
Q

what is actinomyces lung abscess? in which patient group is it expected to be found?

A

alcoholics
- gram positive rod that branches
- causes lung abscesses in immunocompromised patients
- closely associated with Nocardia
- these infections tend to be indolent and go on for a long time
- slow-growing, difficult to treat

histological features:
- basophilic sulphur granules
- gram-positive rods that form branches as they grow

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30
Q

osteomyelities - most common organisms involved, investigations and management

A

staph aureus (except in sickle cell where Salmonella species predominate)

MRI

  • flucloxacillin for 6 weeks
  • clindamycin if penicillin-allergic

BUT
- antimicrobial therapy alone is NOT curative in most cases of osteomyelitis
- continuous drug over a long period of time will lessen the amount of discharge, but it will not cure the disease because it cannot sterilise dead bone or cavities with necrotic content and rigid walls
- removal of devitalised tissues and the prevention of extension of infection by providing adequate drainage is extremely important
- fibrous capsules can form around bacteria which makes it impenetrable to antibiotics and it becomes a chronic source of infection

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31
Q

c. diff - clinical features, what clinical signs would suggest severe and life-threatening infection + management

A

diarrhoea, abdo pain, raised WCC, if severe toxic megacolon

severe:
- raised WCC >15
- acutely raised creatinine (>50% above baseline)
- T> 38.5
- evidence of severe colitis (abdominal or radiological signs)

life-threatening:
- hypotension
- partial or complete ileus
- toxic megacolon
- CT evidence of severe disease

management
- severe: oral vancomycin
- life-threatening: oral vancomycin + IV metronidazole

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32
Q

what are prion diseases?

A
  • prion stands for protein-only infectious agent
  • rare transmissible spongiform encephalopathies in humans and animals
  • they do contain DNA but they are only made of protein
  • when they enter the brain they can trigger a cascade where existing prion proteins become rapidly affected and develop the abnormal isoform of the prion protein
  • this leads to the development of spongiform vacuolisation of the brain
  • results in rapid neurodegeneration
  • currently untreatable
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33
Q

which chromosome has the normal prion gene? what is its function?

A

chromosome 20
function is poorly understood, but has some role in copper metabolism

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34
Q

which are the 3 polymorphisms that we can find on codon 129? which one predisposes to prion disease? describe the process that occurs with prion disease

A

MM - this predisposes to prion disease
MV
VV

(M= methionine, V=valine)

  • the normal protein (PrP) has an alpha-helical structure
  • it is protease-sensitive and sensitive to radiation
  • problems occur when the normal protein transforms into the abnormal version (PrPSc)
  • this has a beta-pleated sheet configuration and is resistant to proteases and radiation so it is difficult to get rid of
  • prion replication: the abnormal protein acts as a template
  • promotes conversion of PrP into PrPsc
  • rapid neurodegeneration
  • trigger is unclear in sporadic cases
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35
Q

prion disease classification

A

sporadic
- Creutzfeldt-Jakob Disease (80%) (older people)

acquired (5%)
- Kuru
- Variant CJD (25-30 yrs)
- iatrogenic CJD (growth hormone from cadavers, blood, surgery)

genetic (15%)
- PRNP mutations

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36
Q

sporadic CJD (Creutzfeldt-Jakob Disease) presentation, investigations, diagnosis

A

rapid dementia with:
- myoclonus
- cortical blindness
- akinetic mutism
- LMN signs

mean age: 65 yrs (45-75)

death within 6 months
cause is uncertain

investigations:
- EEG: periodic, triphasic complexes (non-specific). 2/3 patients have an abnormal EEG
- MRI: increased signal in basal ganglia, increased intensity on DWI MRI of the cortex and basal ganglia
- CSF: raised 14-3-3 protein and S100 (rapid neurodegeneration markers)
- neurogenetics to look for genetic cause

diagnosis:
- brain biopsy is the only way to confirm CJD but this is often done at autopsy
- histology: spongiform vacuolisation

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37
Q

vCJD - presentation, diagnosis

A

young age of onset (26yrs)
median survival time = 14 months
psychiatric onset
- dysphoria
- anxiety
- paranoia
- hallucinations
followed by neurological symptoms
- peripheral sensory symptoms
- ataxia
- myoclonus
- chorea
- dementia

  • MRI: pulvinar sign (high intensity in the putamen)
  • EEG: non-specific slow waves
    (- CSF: 14-3-3 and S100 are NOT useful)
  • neurogenetics: MM at codon 129
  • tonsil biopsy (100% sensitive and specific)
  • brain biopsy
  • autopsy
  • PrPSc type 4T is detectable in the CNS and most lympho-reticular tissues
  • histology: plaques, some areas of vacuolisation
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38
Q

causes of iatrogenic CJD

A
  • human cadaveric growth hormone
  • corneal transplants
  • neurosurgical procedures (e.g., corneal grafts)
  • blood transfusions
  • other surgical procedures (e.g., appendicectomy, tonsillectomy)
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39
Q

Gerstmann-Straussler-Sheinker Syndrome

A
  • slowly progressive ataxia
  • diminished reflexes
  • dementia
  • onset age 30-70 yrs
  • survival 2-10 yrs
  • PRNP P102L (MOST COMMON mutation)
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40
Q

fatal familial insomnia

A
  • untreatable insomnia
  • dysautonomia (blood pressure and heart rate dysregulation)
  • ataxia
  • thalamic degeneration
  • PRNP D178N (with or without extrapyramidal signs, late cognitive decline)
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41
Q

CJD treatment

A

symptomatic:
- clonazepam for the myoclonus
- others: valoproate, levetiracetam

delaying prion conversion:
- quinacrine
- pentosan
- tetracycline

anti-prion antibody:
- prevents peripheral prion replication and blocks progression to disease in infected mice but does NOT get into CNS

depletion of neuronal cellular prion protein:
- prevents onset of disease in mice
- blocks neuronal cell loss and reverses early spongiosis

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42
Q

what is bacteriuria?

A

presence of bacteria in the urine

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43
Q

UTI classification

A

uncomplicated: infection in a structurally and neurologically normal urinary tract

complicated: infection in a urinary tract with functional or structural abnormalities (including indwelling catheters and calculi) - men, pregnant women, children, patients who are hospitalised or in healthcare-associated settings

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44
Q

antibacterial host defences in the urinary tract

A
  • urine (osmolarity, pH, organic acids)
  • urine flow and micturition
  • urinary tract mucosa (bactericidal activity, cytokines)
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45
Q

causes of obstruction of the urinary tract

A

Mechanical
extrarenal:
- valves, stenosis, bands
- calculi
- BPH
intrarenal:
- nephrocalcinosis
- uric acid nephropathy
- analgesic nephropathy
- polycystic kidney disease
- hypokalaemic nephropathy
- renal lesions of sickle cell disease
neurogenic malfunction:
- poliomyelitis
- tabes dorsalis
- diabetic neuropathy
- spinal cord injuries

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46
Q

how does the vesicoureteric reflex (VUR) perpetuate UTI?

A

by maintaining a residual pool of infected urine in the bladder after voiding

(can result in kidney scarring)

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47
Q

investigations for UTI

A

uncomplicated UTI/pyelonephritis:
- urine dipstick
- MSU for urine MC&S
- bloods - FBC, U&E, CRP

further for complicated UTI:
- renal USS
- IV urography

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48
Q

complications of pyelonephritis

A
  • perinephric abscess
  • chronic pyelonephritis (scarring, chronic renal impairment)
  • septic shock
  • acute papillary necrosis
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49
Q

what antibiotics are available for pyelonephritis

A

cefalexin
co-amoxiclav
trimethoprim
ciprofloxacin

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50
Q

hepatitis A - mode of spread, incubation period, diagnostic test

A

faecal-oral
2-6 weeks
IgM anti-hepatitis A virus (NB: if you have had the vaccine, you will have a high IgM AND high IgG but WITHOUT the high ALT)

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51
Q

chronic Hep B treatment

A
  • interferon alpha (this is used in a subset of patients who look like they are more or less clearing the virus by themselves)
  • lamivudine
  • tenofovir
  • entecavir
  • emtricitabine
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52
Q

what is the best way to check whether you have the Hep C virus in your blood

A

HCV RNA

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53
Q

what medication do we use for Hep C

A

peginterferon alpha-2b

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54
Q

hep E treatment

A

supportive
ribavirin

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55
Q

major pathogens causing surgical site infections (SSIs)

A

staphylococcus aureus (MSSA and MRSA)
escherichia coli
pseudomonas aeruginosa

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56
Q

what are the 3 levels of surgical site infections

A
  • superficial incisional (skin and subcutaneous tissues)
  • deep incisional (fascial and muscle layers)
  • organ/space infection (any part of the anatomy other than the incision)
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57
Q

when should antibiotic prophylaxis be given?

A

at the induction of anaesthesia

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58
Q

pre-operative factors that increase the chance of surgical site infection and pre-operative measures to reduce it

A
  • age
  • all remote infection (e.g., pneumonia, UTI)
  • underlying illness
  • diabetes
  • malnutrition
  • low serum albumin
  • radiotherapy and steroids
  • rheumatoid arthritis (stop DMARDs for 4 weeks before to 8 weeks after operation)
  • obesity (adipose tissue is poorly vascularised)
  • smoking (nicotine delays wound healing)
  • pre-op showering
    microorganisms colonising the skin may contaminate exposed tissues and cause an SSI. NO difference in SSI incidence whether chlorhexidine or normal detergent/bar soap is used
  • hair removal
    micro-abrasions caused by shaving may lead to multiplication of bacteria. shaving increases risk of SSIs. electric clipper should be used instead on the day of the surgery with a single-use head, hair should not be removed unless it will interfere with the operation.
  • nasal decontamination
    S aureus carriage is the MOST POWERFUL independent risk factor for SSI following cardiothoracic surgery
  • antibiotic prophylaxis
    should be given at the induction of anaesthesia
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59
Q

intra-operative measures to prevent surgical site infection

A
  • limit number of people in theatre when operating
  • ventilation, maintain positive pressure, filter all air, keep operating doors closed
  • sterilisation of surgical instruments
  • skin preparation (chlorhexidine, povidine-iodine)
  • asepsis and surgical technique (avoid cutting into hollow viscera, remove all dead tissue)
  • normothermia
  • maintain oxygen > 95%
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60
Q

septic arthritis risk factors

A
  • rheumatoid arthritis
  • osteoarthritis
  • crystal arthritis
  • joint prosthesis
  • IV drug use
  • diabetes
  • chronic renal disease
  • chronic liver disease
  • immunosuppression (e.g., steroids)
  • trauma - intra-articular injection, penetrating injury
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61
Q

pathophysiology of septic arthritis

A
  • organisms adhere to synovium
  • bacterial proliferation in the synovial fluid leads to generation of a host inflammatory response
  • joint damage leads to exposure of host derived protein (e.g., fibronectin) to which bacteria can adhere

Bacterial factors:
- S aureus has receptors such as fibronectin-binding protein that recognise selected host proteins

Host factors:
- leucocyte derived proteases and cytokines can cause cartilage and bone damage
- raised intra-articular pressure can impede capillary blood flow and lead to cartilage and bone ischaemia and necrosis
- genetic deletion of macrophage-derived cytokines can reduce the host-response in S. aureus sepsis in animal models
- absence of IL-10 increases the severity of staphylococcus joint disease in knockout mice

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62
Q

investigations for septic arthritis

A
  • blood culture before antibiotics are given
  • synovial fluid for aspiration (MC&S, synovial count > 50,000 WBC/mL)
  • ESR and CRP
  • USS - confirm effusion and guide aspiration
  • CT -check for erosive bone change, periarticular soft tissue extension
  • MRI - joint effusion, articular cartilage destruction, abscess, contiguous osteomyelitis
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63
Q

vertebral osteomyelitis - causes, causative organisms, localisation, symptoms, investigations, treatment

A

causes:
- acute haematogenous spread (bacteraemia)
- exogenous (implantation during disc surgery)

causative organisms:
- staph aureus (48.3%)
- coagulase-negative staphylococcus
- gram-negative rods
- streptococcus

localisation:
- lumbar (43.1%)
- cervical
- cervico-thoracic

symptoms:
- back pain
- fever
- neurological impairment

investigations:
- MRI (90% sensitive)
- blood cultures
- CT-guided/open biopsy

treatment:
- antibiotics (at least 6 wks)
- longer treatment may be needed if undrained abscess/implant-associated

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64
Q

chronic osteomyelitis - presentation, diagnosis, treatment

A

presentation:
- pain
- brodie’s abscess
- sinus tract

diagnosis:
- MRI
- bone biopsy for culture and histology

treatment:
- radical debridement down to living bone
- remove sequestra (dead bone tissue) and infected bone and soft tissue
(lautenbach technique, papineau technique)

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65
Q

what are carbapenemase-producing enterobacteriaceae (CPE)?

A

carbapenemase-producing enterobacteria (CPE) are carbapenem-resistant enterobacteria that contain enzymes called carbapenemases. these break down the antibiotics (carbapenem).
- this is a problem because carbapenems are our last resort antibiotic
- difficult to treat, high mortality
- we do not know the optimal management for CPE bacteraemia or invasive infection

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66
Q

define pyrexia of unknown origin (PUO)

A

fever > 38.3 degrees lasting >3 weeks with an uncertain diagnosis after 7 days in hospital

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67
Q

frequent causes of PUO

A

infection:
- infectious endocarditis
- HIV/AIDS
- TB
- other

non-infectious inflammatory disease:
- polymyalgia rheumatica
- still’s disease
- sarcoidosis
- ANCA-associated vasculitis
- rheumatoid arthritis
- other

malignancy:
- malignant lymphoma
- castleman’s disease
- other

other:
- drug fever
- fraudulent fever
- other

unknown

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68
Q

investigations for PUO

A

routine admission:
- FBC
- U&Es
- total protein
- LFTs
- CRP
- CXR
- blood cultures x3
- urine culture
- HIV test

extra tests:
- CK
- ANA
- ANCA
- RhF
- ferritin
- abdominal imaging (USS/CT)
- CMV EBV serology
- stool cultures + OCP (ova, cyst, parasite exam)

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69
Q

infectious causes of PUO

A

viral
- CMV/EBV
- HIV
- hepatitis A, B, C, D, E

parasites:
- malaria
- amoebic liver abscess
- schistosomiasis
- toxoplasmosis
- trypanosomiasis

fungal:
- cryptococcosis
- histoplasmosis

bacterial:
- mycobacteria (TB, NTM)
- enteric fevers (salmonella, typhi)
- zoonoses

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70
Q

Dukes criteria for infective endocarditis

A

2 major OR 1 major + 3 minor

major:
- persistent bacteraemia (>2 BC pos)
- echocardiogram: vegetation
- positive serology for Bartonella, Coxiella or Brucella

minor:
- predisposition (murmur, IV drug use)
- inflammatory markers (fever, high CRP)
- immune complexes: splinters, RBCs in urine
- embolic phenomena: Janeway lesions, CVA
- atypical echo
- 1 positive BC

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71
Q

giant cell arteritis

A
  • age > 50 yrs
  • headache
  • jaw claudication
  • scalp tenderness
  • ischaemic tongue
  • ESR > 45 (not raised in some cases)
  • 50% will have a change in vision at presentation (often minor and fluctuating)
  • high risk of sight impairment/stroke
  • temporal artery biopsy (GOLD STANDARD)
  • PET is useful
  • TREAT IMMEDIATELY - high dose prednisolone
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72
Q

adult onset stills and macrophage activation syndrome (MAS)

A

presents with a salmon pink rash
can be mistaken for a drug reaction
ferritin is often VERY HIGH

major criteria:
- T > 39 for > 1 week
- leukocytosis > 10,000/mm3 (80% granulocytes)
- typical rash
- arthralgias > 2 wks

minor:
- sore throat
- lymphadenopathy and/or
- splenomegaly/hepatomegaly
- abnormal liver function studies, particularly elevations in AST, ALT, LDH
- negative tests for ANA and rheumatoid factor

exclusion:
- infections, esp. sepsis
- epstein-barr infection
- malignancy
- inflammatory diseases

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73
Q

what are zoonoses?

A

diseases that pass between people and animals

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74
Q

transmission of zoonoses

A

everyday contact with animals
- scratches and bites
- traditional pets = cats, dogs
- less traditional = reptiles, rodents, exotic birds, chickens, spiders

by-products (faeces/urine)
- contaminated soil
- litter

foodstuffs:
- carcass processing
- milk and milking
- raw/undercooked meats

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75
Q

campylobacter - reservoir, transmission, clinical presentation, investigations, management

A

reservoir:
- poultry
- cattle

transmission:
- contaminated good

clinical presentation:
- diarrhoea
- bloating
- cramps

investigations:
- stool culture

management:
- supportive

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76
Q

salmonella - reservoir, transmission, clinical presentation, investigations, management

A

reservoir:
- poultry
- reptiles/amphibians

transmission:
- contaminated food
- poor hygiene

clinical presentation:
- diarrhoea
- vomiting
- fever

investigations:
- stool culture

management:
- SUPPORTIVE
- ciprofloxacin
- azithromycin

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77
Q

bartonella henselae

A

reservoir:
- kittens > cats

transmission:
- scratches
- bites
- licks of open wounds
- fleas

causes 2 diseases:
- cat scratch disease
- bacilliary angiomatosis

cat scratch disease (immunocompetent)
- presentation: macule at site of inoculation, becomes pustular, regional adenopathy, systemic symptoms (fever, night sweats, weight loss)
- investigations: serology
- management: erythromycin, doxycycline

bacillary angiomatosis (immunocompromised)
- presentation: skin papules, disseminated multi-organ and vasculature involvement, leads to bursting of blood vessels in various organs and tissues, can be fatal
- investigations: histopathology, serology
- management: erythromycin, doxycycline PLUS rifampicin

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78
Q

toxoplasmosis - reservoir, transmission, presentation, investigations, management

A

reservoir:
- cats
- sheep

transmission:
- infected meat
- faecal contamination

presentation:
- fever
- adenopathy
- still-birth
- infants with progressive visual, hearing, motor and cognitive issues
- seizures
- neuropathy (immunocompromised)

investigations:
- serology

management:
- spiramycin
- pyrimethamine + sulfadiazine

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79
Q

brucellosis - reservoir, transmission, presentation, investigations, management

A

reservoir:
- cattle
- goats

transmission:
- unpasteurised milk
- undercooked meat
- mucosal splash
- aerosolisation/inhalation

presentation:
- fever
- back pain
- orchitis
- focal abscesses (psoas, liver)
(NB: looks a bit like TB)

investigations:
- blood/pus culture
- serology
(the lab should be warned that the sample might be brucellosis)

management:
- doxycycline AND gentamicin/rifampicin

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80
Q

coxiella burnetti (Q fever) - reservoir, transmission, presentation, investigations, management

A

reservoir:
- goats
- sheep
- cattle

transmission:
- aerosolisation/inhalation of secretions
- waste
- milk of infected animals
- unpasteurised milk

presentation:
- fever
- flu-like illness
- pneumonia
- hepatitis
- endocarditis
- focal abscess (para-vertebral, discitis)

investigations:
- serology

management:
- doxycycline

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81
Q

rabies (lyssa virus) - reservoir, transmission, presentation, investigations, management

A

reservoir:
- dogs
- cats
- bats

transmission:
- bites
- scratches
- contact with infected fluid

presentation:
- seizures
- excessive salivation
- agitation
- confusion
- fever
- headache
NB: once symptoms start, there is a near 100% mortality

investigations:
- serology
- brain biopsy

management:
- immunoglobulin
- vaccine

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82
Q

rat bite fever - reservoir, transmission, presentation, investigations, management

A

reservoir:
- rats

transmission:
- bites
- contact with infected urine or droppings

presentation:
- fever
- polyarthralgia
- maculopapular
progressing to purpuric rash
- can progress to endocarditis

investigations:
- joint fluid microscopy and culture
- blood culture

management:
- penicillins

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83
Q

hentavirus pulmonary syndrome - reservoir, transmission, presentation, investigations, management

A

reservoir:
- deer mouse - Sin Nombre virus
- white footed mouse - Sin Nombre virus
- cotton rat - Black canal virus
- rice rat - Bayou virus

transmission:
- contact with infected urine or droppings
- aerosolisation

presentation:
- fever
- myalgia
- flu-like illness
- respiratory failure (in USA)
- bleeding and renal failure (in SE Asia)

investigations:
- serology
- PCR

management:
- supportive

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84
Q

viral haemorrhagic fever - reservoir, transmission, presentation, investigations, management

A

reservoir:
- ebola - bats?
- marburg - bats?
- lass - rats
- crimean-congo haemorrhagic fever - ticks

transmission:
- contact with fluids of infected

presentation:
- fever
- myalgia
- flu-like illness
- bleeding

investigations:
- serology
- PCR

management:
- supportive

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85
Q

investigations in patients with zoonoses

A

culture
- blood
- pus
- CSF
- stool

serology:
- targeted
- SAVE some serum

PCR

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86
Q

give examples of upper and lower respiratory tract infections

A

URTI:
- sinusitis
- tonsilitis

LRTI:
- bronchitis
- pneumonia
- empyema
- bronchiectasis
- lung abscess

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87
Q

what makes a patient more suscpetible to respiratory diseases?

A
  • poor swallow (CVA, muscle weakness, alcohol)
  • abnormal ciliary function (smoking, viral infection, Kartagener’s)
  • abnormal mucous (cystic fibrosis)
  • dilated airways: bronchiectasis
  • defects in host immunity (HIV, immunosuppression)
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88
Q

pneumonia presentation

A

fever
cough
pleuritic chest pain
shortness of breath

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89
Q

causes of community acquired pneumonia (CAP)

A

typical (85%)
- streptococcus pneumoniae
- haemophilus influenzae

atypical (15%)
- legionella
- mycoplasma
- coxiella burnetti (Q fever) - exposure fo farm animals
- chlamydia psittaci (psittacosis) - exposure to birds, splenomegaly, rash, haemolytic anaemia

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90
Q

CAP - examination findings and investigations

A

examination findings:
- pyrexia
- tachycardia
- tachypnoea
- cyanosis
- dullness to percussion
- bronchial breathing
- crackles

investigations:
- FBC
- U&Es
- CRP
- blood cultures
- sputum MC&S
- ABGs
- CXR

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91
Q

CURB-65

A

confusion
urea > 7 mmol/L
RR > 30
BP < 90 systolic, <60 diastolic
65+ years

2 = consider admitting
2-5 = manage as SEVERE pneumonia and consider ITU admission

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92
Q

bronchitis - presentation, organisms, treatment

A

presentation:
- cough
- fever
- increased sputum production
- increased shortness of breath

mainly occurs in smokers
CXR is usually NORMAL

organisms:
- viruses
- strep pneumoniae
- haemophilus influenzae
- moraxella catarrhalis

treatment:
- bronchodilation
- physiotherapy
- antibiotics

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93
Q

atypical pneumonia organisms

A

(organisms without a cell wall)
- mycoplasma
- legionella
- chlamydia
- coxiella

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94
Q

legionella pneumophila pneumonia

A

aerosol spread
environmenal outbreaks
associated with:
- confusion
- abdominal pain
- diarrhoea

lymphopaenia
hyponatraemia

investigation: urinary antigens

sensitive to macrolides (clarithromycin/erythromycin)

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95
Q

coxiella burnetti pneumonia

A
  • common in domesticated farm animals
  • transmitted by aerosol or milk
  • investigation: serology
  • sensitive to macrolides (clarithromycin/erythromycin)
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96
Q

chlamydia psittaci pneumonia

A
  • spread from birds by inhalation
  • investigation: serology
  • sensitive to macrolides (clarithromycin/erythromycin)
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97
Q

pneumonia - failure to improve on treatment reasons

A
  • empyema/abscess
  • proximal obstruction (tumour)
  • resistant organisms (travel is important)
  • not receiving/absorbing antibiotics
  • immunosuppression
  • other diagnosis (lung cancer, cryptogenic organising pneumonia)
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98
Q

TB pneumonia - cues, CXR, staining

A

cues:
- ethnicity
- prolonged prodrome
- fevers
- weight loss
- haemoptysis

CXR:
- classicaly upper lobe cavitation

staining:
- Ziehl-Neelsen or auramine stain
- red rods: acid-fast bacilli

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99
Q

Hospital-acquired pneumonia - causative organisms

A
  • Enterobacteriaciae (e.g., E coli, K pneumoniae)
  • staphylococcus aureus
  • pseudomonas spp
  • haemophilus influenzae
  • acinetobacter baumanii
  • fungi (cadida spp)
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100
Q

pneumocystis jirovecii pneumonia

A

protozoan
ubiquitous in the environment
insidious onset

presentation:
- dry cough
- weight loss
- SoB
- malaise
- NB: the walk test (attaching an oxygen saturation probe and asking the patient to walk) will show desaturation on exertion

CXR - bat wing shadowing

investigations: bronchoalveolar lavage
treatment: co-trimoxazole (septrin)
- prophylaxis: co-trimoxazole

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101
Q

apergillus fumigatus

A

allergic bronchopulmonary aspergillosis
- chronic wheeze
- eosinophilia
- bronchiectasis

aspergilloma:
- fungal ball, often in pre-existing cavity
- may cause haemoptysis

invasive aspergillosis:
- immunocompromised
- treatment: amphotericin B

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102
Q

natural history of TB

A

primary TB
- usually asymptomatic
- Ghon focus (granuloma in the lungs)
- controlled by cell-mediated immunity
- rare allergic reactions include erythema nodosum
- occasionally causes disseminated/miliary TB

latent TB

reactivation of TB

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103
Q

TB presentation

A
  • fever
  • weight loss
  • night sweats
  • pulmonary (cough, haemptysis)
  • malaise
  • anorexia
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104
Q

influenza life cycle

A
  • the virus is particularly vulnerable during the transmission phase when it is going in between people
  • they attach to cells via sialic acid receptors
  • they enter through endosomes
  • the acidity of the endosome triggers a fusion event by which it releases its genome into the cell
  • the genome then travels to the nucleus and takes over host factors to drive transcription and translation
  • new viral products are produced (proteins and genome)
  • they will assemble at the surface of the cell and bud off to produce hundreds of copies of the virus
105
Q

how does the influenza virus infect humans

A
  • the haemaglutinin (HA) protein must be cleaved for the virus to be able to fuse with the endosome membrane and release its genome into the host cells
  • Human airway tryptase in the lung lining is capable of cleaving HA, however, this enzyme is not present in other parts of the body
106
Q

what mutation allows animal influenza to cross into humans?

A

mutation in the polymerase protein (PB2 627K)

107
Q

influenza virus - what is antigenic shift, reassortment of genes so that an animal virus can start infecting humans too

A
  • a single cell is infected by both a human virus and a bird virus
  • they then shuffle their RNA resulting in production of a bird virus with the capability of infecting a human
  • this is a quick way of acquiring the ability to infect humans and becoming a pandemic
  • this is an example of an antigenic shift
108
Q

what antivirals can be used for influenza?

A
  • amantadine
  • neuraminidase inhibitors
    (tamiflu (oseltamivir), relenza (zanamivir), peramivir)
  • polymerase inhibitors
    (favipiravir, baloxavir)
109
Q

which is the target of amantadine? which viruses is not effective against?

A

targets M2 ion channel

does not work against influenza B, pH1N1 or seasonal H3N2

110
Q

why do we need a different influenza vaccine every year? what would be the ideal solution to this?

A
  • most antibodies bind to the head of the HA molecule
  • there is another antibody-inducing region in the stalk of HA
  • the antibody binding sites of the head region are very plastic and change every year
  • However, the antibody binding site in the stalk appears to be invariant
  • so, if we could produce antibodies against that invariable patch, those antibodies will cross react with every type of influenza
111
Q

what are directly-acting antivirals (DAAs)?

A
  • they are small molecule inhibitors that can block the production or action of viral-encoded proteins and inhibit viral replication
  • viral-encoded proteins are a target for antiviral drugs (e.g., protease inhibitors, polymerase inhibitors, integrase inhibitors)
112
Q

what is an alternative approach to antiviral therapy? state some limiting factors of antiviral therapy

A

help the immune system to clear the virus or try and reduce inflammation (which can cause disease)
- this is achieved by giving exogenous immunomodulators (e.g,, interferon, IV immunoglobulins)
- normally, viral replication is detected by pattern-recognition receptors which trigger innate immune responses leading to production of factors such as type 1 interferons
- this antiviral immune response can be boosted by giving immunomodulators

Limiting factors of antiviral therapy:
- the host immune resopnse is critical (transplant/HIV patients is difficult)
- adherence to treatment
- antiviral drug resistance
- drug toxicity

113
Q

varicella zoster virus - presentation, treatment

A
  • chickenpox is caused by primary infection by VZV
  • most cases are uncomplicated in children
  • adults are more susceptible to complications (e.g., pneumonitis)
  • can cause severe disease in the immunocompromised
  • reactivation (from dorsal root ganglia) causes shingles
  • in immunocompetent patients, shingles will follow a dermatomal distribution (possible complication: post-herpetic neuralgia)
  • in immunocompromised patients, shingles can be multi-dermatomal or cause disseminated infection with severe complications

treatment:
- aciclovir (PO or IV)

114
Q

how does aciclovir work?

A
  • nucleoside analogue that gets incorporated into the growing chain of viral DNA
  • when this happens, further gene elongation becomes blocked
  • so, this class of drugs is also known as “chain terminators”
  • it requires activation by viral thymidine kinase (which is only found in host cells that are infected by the virus)
  • aciclovir has a higher affinity for viral DNA polymerase than the host DNA polymerase
115
Q

indications for treatment of VZV

A
  • chickenpox in adults (risk of pneumonitis)
  • shingles in adults > 50 years (risk of post-herpetic neuralgia)
  • primary infection or reactivation in an immunocompromised patient
  • neonatal chickenpox
  • if increased risk of complications (e.g., underlying lung disease, eye involvement)
116
Q

cytomegalovirus (CMV) - presentation, histology, treatment

A
  • opportunistic virus that can cause severe disease in the immunocompromised
  • after primary infection, CMV tends to lie latent in blood monocytes and dendritic cells
  • it can be reactivated following immunosuppression
  • it can be shed in asymptomatic patients via saliva, urine, semen and cervical secretions
  • consequences in the immunocompromised: bone marrow suppression, retinitis, pneumonitis, hepatitis, colitis, encephalitis

histology:
- typically shows owl’s eye inclusions

treatment:
- ganciclovir (IV)
- valganciclovir (PO)
- foscarnet (IV/intravitreal)
- cidofovir (IV)

117
Q

ganciclovir (IV) - mechanism, uses, side effects

A
  • requires activation by the viral UL97 kinase enzyme (like aciclovir)
  • effective against a range of herpesviruses but tend to mainly be used to treat CMV infection in immunocompromised patients
  • in patients with CMV pneumonitis, ganciclovir is used in conjuction with IV immunoglobulins
  • side effects: BM toxicity, renal and hepatic toxicity
    NB: this limits its use in bone marrow transplant patients
118
Q

foscarnet - uses, mechanism of action, side effect

A
  • non-competitive inhibitor of viral DNA polymerase
  • does not require activation
  • effective against many herpesviruses
  • tends to be used on CMV infection where ganciclovir is contraindicated (e.g., neutropaenia)
  • side effect: nephrotoxicity
119
Q

cidofovir - uses, mechanism of action, side effects

A
  • nucleotide analogue
  • competitive inhibitor of viral DNA synthesis
  • does not require activation
  • 3rd line treatment of CMV disease in the immunocompromised
  • side-effect: nephrotoxicity
120
Q

strategies for treatment of CMV in transplant patients

A

treat established disease once it has been developed (high mortality in BM transplant patients)

prophylaxis with ganciclovir or valganciclovir
- side effects: bone marrow toxicity
- mostly used for solid organ transplant

pre-emptive therapy (for BM transplant patients)
- monitoring the appearance of CMV on PCR in the blood
- starting ganciclovir, valganciclovir or foscarnet when the viral load reaches a certain threshold

new drugs: maribavir, letermovir

121
Q

what are the 2 main surface proteins of influenza virus?

A

haemaglutinin (HA) and neuraminidase (NA)

122
Q

neuraminidase inhibitors - examples, uses, indications

A

oselatmivir (Tamiflu), zanamivir (relenza)

  • effective against influenza A and B
  • indicated for all patients who are unwell enough to be admitted to hospital with an influenza virus-related respiratory disease

indicated in the community if all 3 apply:
- national surveillance indicates influenza is circulating
- patient is in a risk-group
- within 48 hours of symptom onset (36 hours for zanamivir)

123
Q

Respiratory Syncytial Virus (RSV) treatment

A

Ribavirin
- nucleoside analogue
- oral
- inhibits viral RNA synthesis
- clinical efficacy is in doubt

IV immunoglobulin
- derived from pooled donors
- often used as an adjunct to treatment of viral pneumonitis in the immunocompromised

Palivizumab
- monoclonal antibody against RSV
- used prophylactically in the winter months for the prevention of serious lower respiratory tract disease caused by RSV in high-risk infants (e.g., preterm, heart or lung disease, SCID)

124
Q

BK virus - presentation, treatment of BK haemorrhagic cystitis, treatment of BK nephropathy

A
  • polyomavirus
  • primary BK infection in childhood causes minimal symptoms but leads to lifelong carriage in the kidneys and urinary tract
  • causes problems in the immunocompromised
  • BM transplants: haemorrhagic cystitis and sometimes nephritis
  • renal transplants: BK nephritis and ureteric stenosis

treatment of BK haemorrhagic cystitis:
- bladder washouts
- reduce immunosuppression
- cidofovir IV

treatment of BK nephropathy:
- reduce immunosuppression
- IV immunoglobulin
NB: cidofovir cannot be used because it is nephrotoxic

125
Q

adenovirus treatment

A
  • cidofovir IV
    -brincidofovir (less toxicity, not currently licensed, ongoing clinical trials)
126
Q

implications of antiviral drug resistance

A
  • treatment failure
  • need to use second-line drugs
  • cross-resistance with other antivirals
127
Q

prevention of antiviral drug resistance

A
  • combination drug therapy can achieve maximal suppression of viral replication (this is standard for HIV and hepatitis treatment)
  • increase adherence to treatment (lower pill burden etc)
  • in HIV, the virus is sequenced to identify the baseline resistance in order to select the optimum treatment regimen
128
Q

what is herd immunity? what is herd immunity threshold?

A

= form of immunity that occurs when vaccination of a significant proportion of the population provides a measure of protection for individuals that are not immune

herd immunity threshold = 1 - 1/Ro
(this is the percentage of fully immune individuals required to stop the spread of disease)

129
Q

which are the 3 main types of memory cells

A
  • memory B cells
  • memory killer T cells
  • memory T helper cells
130
Q

what are protective antigens?

A

these are microbial components that give rise to a protective immune response to future infection

  • these are often used in the development of vaccines
  • some may require an adjuvant to make it more immunogenic
131
Q

types of vaccines

A
  • inactivated
  • live attenuated
  • toxoid vaccines
  • subunit
  • conjugate
  • heterotypic
  • monovalent
  • multivalent
132
Q

inactivated vaccines

A
  • whole microorganism is destroyed by heat, chemicals, radiation or antibiotics
  • it has no risk of causing infection in the host
  • however, it may not produce a very strong or long-lasting immune response

examples:
- influenza
- polio
- cholera

133
Q

live attenuated vaccines

A
  • live organisms are modified to be less virulent
  • there is a risk of virulence
  • it is avoided in pregnant women and immunocompromised patients

examples:
- MMR
- yellow fever

134
Q

toxoid vaccines

A

inactivated toxin components

examples:
- diphtheria
- tetanus

135
Q

subunit vaccines

A
  • protein components of the microorganism or synthetic virus-like particles are used
  • they lack viral genetic material and are unable to replicate

examples:
- hep B
- HPV

136
Q

conjugate vaccines

A
  • poorly immunogenic antigens are paired with a protein that is highly immunogenic (adjuvant)

examples:
- haemophilus influenzae type B

137
Q

heterotypic vaccines

A
  • using pathogens that infect other animals but do NOT cause disease in humans or causes mild disease

examples:
- BCG

138
Q

monovalent vs multivalent vaccines (meaning)

A

monovalent = targeting one strain
multivalent = targeting several strains

139
Q

components of a vaccine

A
  1. active components
  2. adjuvants
    - added to enhance the body’s immune response to the vaccine (thought to keep the antigens near the site of injection)
    - aluminium hydroxide is a commonly used adjuvant
  3. antibiotics
    - used in the manufacturing process of the vaccine to prevent bacterial contamination
    - they are then later removed, only residual quantities remain
  4. stabilisers
    - substances that are added to the vaccine to keep it chemically stable for transport for the site of production to site of use
    ex. inorganic magnesium salts (magnesium sulfate, magnesium chloride) or mixtures of lactulose, sorbitol and gelatin
  5. preservatives
    - help prevent contamination of vaccines
    - particularly important for multi-dose/multi-use vaccines where you don’t want the vials to be contaminated
  6. trace components
    - left-over from the vaccine production process
140
Q

what are the determinants of antibody response to a vaccine?

A
  • vaccine type (live attenuated > inactivated etc)
  • antigen nature
  • vaccination schedule
141
Q

DTP vaccine - serious reactions and causality

A

probably causal:
- encephalopathy shock

established causality:
- anaphylaxis

142
Q

OPV/IPV vaccine - serious reactions and causality

A

probably causal:
- Guillain-Barre syndrome (GBS)

established causality:
- poliomyelitis (OPV)

143
Q

congenital toxoplasmosis

A

may be asymptomatic (60%) at birth but may still go on to have long-term sequelae such as:
- deafness
- low IQ
- microcephaly

40% of babies are symptomatic at birth:
- choroidoretinitis
- microcephaly/hydrocephalus
- intracranial calcifications
- seizures
- hepatosplenomegaly/jaundice

144
Q

congenital rubella syndrome

A
  • effect on the foetus depends on the time of infection
  • mechanism: mitotic arrest of cells, angiopathy, growth inhibitor effect
  • classical triad:
    a) cataracts
    b) congenital heart disease (PDA is most common)
    c) deafness

other features:
- microphthalmia
- glaucoma
- retinopathy
- ASD/VSD
- microcephaly
- meningoencephalopathy
- developmental delay
- growth retardation
- bone disease
- hepatosplenomegaly
- thrombocytopenia
- rash

145
Q

Herpes Simplex Virus in the neonate

A
  • this can spread to the neonate through the genital tract
  • this can cause blistering rash
  • it can cause disseminated infection with liver dysfunction and meningoencephalitis
  • infection control is particularly important because you don’t want this to spread
146
Q

early-onset neonatal infection - definition, organisms responsible, brief classification of organisms

A

within 48 hours of birth

a) Group B Streptococcus
- gram-positive coccus
- catalase-negative
- beta-haemolytic
- 1/3 of women are colonised
- in neonates, can cause: bacteraemia, meningitis, disseminated infection

b) Escherichia coli
- gram-neg rods
- in neonates, can cause: bacteraemia, meningitis, UTI

c) Listeria monocytogenes
- gram-positive rods
- can cause sepsis in both the mother and baby

147
Q

risk factors for early-onset neonatal sepsis

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

148
Q

antibiotics used for early-onset neonatal sepsis

A

benzylpenicillin & gentamicin

149
Q

late-onset neonatal sepsis - definition, organisms, antibiotics

A

after 48-72 hours

causes:
- coagulase-negative staphylococci (CoNS)
- group B strep
- E coli
- Listeria monocytogenes
- staph aureus
- enterococcus sp.
- gram-negatives: Klebsiella, Enterobacter, Pseudomonas aeruginosa, Citrobacter koseri
- candida

cefotaxime + vancomycin

150
Q

main cause of meningitis

A

Men B

151
Q

streptococcus pneumoniae

A

gram-positive
diplococcus
alpha-haemolytic

152
Q

haemophilus influenzae

A

gram-negative rod
grows glossy colonies on blood agar

153
Q

mycoplasma pneumoniae - presentation, treatment

A

tends to affect older children (> 4 yrs)
- treated with macrolides (azithromycin)
- incubation period of 2-3 weeks

mainly asymptomatic

classical presentation:
- fever
- headache
- myalgia
- pharyngitis
- dry cough

extrapulmonary manifestation:
- haemolysis
- neurological (encephalitis, aseptic meningitis, peripheral neuropathy, transverse myelitis, cerebellar ataxia)
- cardiac
- polyarthralgia, myalgia, arthritis
- otitis media
- bullous myringitis

154
Q

classification of fungi and examples

A

yeast:
- candida
- cryptococcus
- histoplasma (dimorphic)

moulds:
- aspergillus
- dermatophytes
- agents of mucormycosis

NB: some fungi are dimorphic and can change between being yeast and moulds

155
Q

diagnosis of candidiasis

A

a) swabs

b) blood cultures for candidaemia

c) beta-D glucan assay (serology)
sometimes used to look for evidence of invasive Candida infection

d) imaging
e.g., for hepatosplenic candidiasis

156
Q

management of candidiasi

A
  • treat for at least 2 weeks of antifungals from the first negative blood cultures
  • echo and fundoscopy (look for evidence of endocarditis and enophthalmitis)
  • echinicandins are used empirically and for non-albicans Candida infections
  • fluconazole is still effective for Candida albicans
  • there are some specific situations in which you need to use a certain type of antifungal because of its pharmacokinetics/pharmacodynamics (e.g., echinicandins don’t penetrate well into the CNS so you have to use Ambisome instead)
157
Q

treatment of cryptococcus

A

ambisome

(it is susceptible to fluconazole and amphotericin. it is inherently resistant to echinicandins)

158
Q

life cycle of cryptococcus

A
  • the spores are ubiquitous
  • it will be inhaled and then, in immunocompromised patients, it will disseminate
  • there is a predilection for the CNS
159
Q

microscopy of cryptococcus

A
  • cryptococcus has a very distinct capsule around the yeast
  • India ink is used to stain for Cryptococcus
  • the ink will stain everything black except for the capsule around the yeast
  • the capsule is NOT always present (if the organism is not under any form of stress it will not need the capsule)
  • India ink is not used very frequently anymore
  • instead, an enzyme immunoassay (EIA) to look for components of the capsule are used now
  • cryptococcus can grow in culture but the antigen test is much quicker
160
Q

diseases caused by Aspergillus

A
  • mycotoxicosis due to ingestion of contaminated foods
  • allergy (e.g., wheeze)
  • colonisation without extension in preformed cavities and debilitated tissues (e.g., Aspergillus can colonise a cavity that was produced by TB)
  • invasive disease
  • systemic and fatal disseminated disease
161
Q

diagnosis of Aspergillosis

A
  • blood test
  • serology (look for IgE [allergic response), antigen detection (galactomannan)]
  • PCR
  • histology
  • culture
162
Q

management of Aspergillosis

A

amphotericin (mainstay of treatment)
at least 6 weeks of therapy

voriconazole
ambisome
NB: fluconazole has POOR activitiy against moulds

163
Q

give 3 examples of dermatophyte infections

A
  • ringworm
  • tinea
  • nail infections
164
Q

tinea pedis (Athlete’s foot) aetiological agents

A
  • trichophyton rubrum
  • trichophyton interdigitale
  • epidermophyton floccosum (less commom)
165
Q

tinea cruris (in the groin area) aetiological agents

A
  • trichophyton rubrum
  • epidermophyton floccosum
166
Q

tinea capitis (on the head) aetiological agents

A
  • trichiphyton rubrum
  • trichophyton tonsurans
167
Q

onychomycosis (thickened nails) - aetiological agents, management

A
  • trichophyton spp.
  • epidermophyton spp.
  • microsporum spp.
  • may require long course of treatment
  • usually treated with nail lacquers
  • if this doesn’t work, then systemic treatment with turbinafine
  • itraconazole may also be used
  • diagnosed by taking skin scrapings
  • microscopy is used to identify the organisms
168
Q

what is pityriasis vesicolor? cause?

A
  • characterised by discolouration of skin
  • caused by Malassezia furfur
169
Q

mucormycosis

A

= group of moulds that can cause very severe and invasive disease

affects:
- immunocompromised patients
- poorly controlled diabetics

  • characterised by cellulitis of the orbit and face which progresses with discharge and black pus from the palate and nose
  • black eschards may be seen as the fungus invades and destroys the tissues
  • retro-orbital extension produces proptosis, chemosis, ophthalmoplegias and blindness
  • as the brain is involved, it can cause decreasing levels of consciousness
  • invasion of brain is called rhinocerebral mucormycosis

aetiological agents:
- rhizopum spp.
- rhizomucor spp.
- mucor spp.

SURGICAL EMERGENCY
- all the dead and necrotic tissue needs to be debrided
- requires early referral to ENT
- antifungal agents may be used (amphotericin high dose, posaconazole)

170
Q

different types of antifungals + give examples

A

A) Cell membrane antifungals
1. Polyelene antibiotics
- amphotericin B, lipid formulations
- nystatin (topical)

  1. Azole antifungals
    - ketoconazole
    - itraconazole
    - fluconazole
    - voriconazole
    - miconazole, clotrimazole

B) DNA/RNA synthesis antifungals
- pyrimidine analogues (flucytosine)

C) Cell wall antifungals
- echinocandins (caspofungin acetate)

171
Q

azole: mechanism of action

A
  • inhibit ergosterol production
  • they do this by inhibiting cytochrome P450 enzyme lanosterol 14-alpha-demethylase which converts lanosterol to ergosterol
  • there is some cross-reactivity with mammalian CYP450 enzymes. this can lead to drug interactions and impairment of steroidogenesis (ketoconazole, itraconazole)
  • by inhibiting the ergosterol pathway, you will get an accumulation of toxic steroids in the cell membrane which will result in cell death
172
Q

types of azoles

A

water-soluble triazoles
- fluconazole (good against Candida and Cryptococcus)
- Voriconazole (similar to fluconazole but has improved activity against Aspergillus)

lipophilic triazoles
- itraconazole (useful against dermatophytes)
- posaconazole (has activity against mucor)

173
Q

echinocandin antifungals - examples, mechanism, active against

A

examples:
- caspofungin
- micafungin
- anidulafungin

important: Cryptococcus is inherently RESISTANT to echinicandins

mechanism:
- cyclic lipopeptide antibiotic
- inhibit beta-(1,3) D-glucan synthase
- this inhibits the production of beta-D glucan which is a component of the fungal cell wall
- this results in osmotic fragility

active against:
- cadida species (inc. non-albican isolates that are resistant to fluconazole)
- aspergillus species
- NO coverage for Cryptococcus neoformans

174
Q

polyene antifungals

A

main polyene = amphotericin B
- it is put into liposomes in a lot of different formulations to try and reduce toxicity and improve penetration
- it binds to ergosterol in the fungal cell membrane
- this creates transmembrane channels leading to electrolyte leakage
- this leads to fungal cell death

active against most fungi except:
- aspergillus terreus
- scedosporium spp.

nephrotoxicity:
- most significant delayed toxcitiy
- renovascular and tubular mechanism
- enhanced in patients who are volume-depleted or who are on concomitant nephrotoxic agents

175
Q

flucytosine (+ clinical uses, side effects)

A
  • restricted spectrum of activity
  • inhibits DNA in the fungal cells
  • resistance is due to:
    a) decreased uptake (permease activity)
    b) altered 5-FC metabolism (cytosine deaminase or UMP pyrophosphorylase activity)

clinical uses:
- monotherapy is now limited
- candidiasis and cryptococcosis (in combination with amphotericin B or fluconazole)

side effects:
- infrequent: D&V, changes in LFTs, blood disorders
- blood concentrations need monitoring when used in conjuction with amphotericin B

176
Q

viral infections in pregnancy - manigestations in congenital, perinatal and postnatal infection

A

congenital:
- growth retardation - low birth weight
- congenital malformations
- fetal loss - stillbirths

perinatal:
- meningitis
- septicaemia
- pneumonia
- preterm labour

postnatal:
- meningitis
- septicaemia
- conjuctivitis
- pneumonitis

177
Q

what do we mean by teratogenicity during pregnancy

A
  • decrease in rate of cell division (structural malformations)
  • decreased in overall number of cells (small babies)
  • interference with the development of key organs
  • tissue necrosis due to viral replication
178
Q

congenital rubella syndrome

A

most common: sensorineural hearing loss

classic triad:
- microcephaly
- patent ductus arteriosus
- cataracts

other neurological problems:
- psychomotor/mental retardation
- meningoencephalitis
- microcephaly/intracranial manifestations

opthalmic problems:
- cataract, glaucoma
- retinopathy, microphthalmia

intrauterine growth retardation

congenital heart defects (most commonly PDA)

hepatosplenomegaly

thrombocytopaenic purpura

179
Q

rubella - risk of congenital abnormalities based on timing of pregnancy

A

0-12 weeks
- organogenesis
- >90% CRS
- 20% foetal loss

13-20 weeks
- CNS development
- 15% deafness and retinopathy

> 20 weeks
- growth
- low risk of deafness and retinopathy

NB: the main issue occurs when infection happens in the 1st trimester

180
Q

how is congenital CMV infection defined

A

detection of CMV from bodily fluids (normally urine and saliva) or tissues within the first 3 weeks of life

181
Q

cytomegalic inclusion disease

A

CNS abnormalities
- microcephaly
- mental retardation
- spasticity
- epilepsy
- periventricular calcification

eye
- chorioretinitis
- optic atrophy

ear
- sensorineural deafness (leading cause)

liver
- hepatosplenomegaly
- jaundice (due to hepatitis)

lung
- pneumonitis

heart
- myocarditis

thrombocytopaenic purpura

haemolytic anaemia

late sequlae in individuals who are asymptomatic at birth include hearing defects and reduced intelligence

182
Q

CMV in pregnancy - prevention and treatment

A

NO vaccine
universal precautions

congenital CMV with significant organ disease:
- valganciclovir (oral) or ganciclovir (IV) for 6 months
- audiology follow-up until 6 years of age
- ophthalmology review

183
Q

herpes simplex virus - classification of maternal infection

A
  • primary infection
  • first episode, non-primary infection
  • recurrent infection
  • symptomatic/asymptomatic
184
Q

HSV - factors influencing neonatal transmission

A
  • type of maternal infection (primary infection poses the greatest risk of transmission)
  • maternal antibody status (neutralising antibodies)
  • duration of rupture of membranes
  • integrity of mucocutaneous barriers (e.g., use of foetal sclap electrodes)
  • mode of delivery (C-sections have lower risk and are preferred)
  • timing of pregnancy (3rd trimester is the highest risk)
185
Q

HSV - manifestation of neonatal disease

A
  • skin, eye and mouth (SEM) disease (45%)
  • CNS disease with or without SEM (30%)
  • disseminated infection involving multiple organs (25%) [high mortality]
186
Q

HSV - clinical presentation of intra-partum and post-partum infection

A

disseminated disease:
- DIC
- pneumonia
- hepatitis
- CNS involvement (60-75%)

encephalitis (CNS disease):
- seizures
- lethargy
- irritability
- poor feeding
- temperature instability

skin, eyes and/or mouth (SEM) disease

187
Q

HSV treatment

A

high-dose IV aciclovir (60mg/kg/day) in 3 divided daily doses. 21 days minimum for disseminated or CNS disease

repeat LP and CSF PCR
continue with PCR until PCR-negative
14 days minimum in SEM disease

monitor neutrophil count (can cause a drop in count)

188
Q

complications of intrauterine VZV (varicella zoster virus)

A
  • congenital varicella syndrome
  • neonatal varicella
  • herpes zoster during infancy or early childhood
189
Q

congenital varicella syndrome

A
  • low birth weight
  • cutaneous scarring
  • limb hypoplasia
  • microcephaly
  • cortical atrophy
  • chorioretinitis
  • cataracts
190
Q

Measles - symptoms

A
  • prodrome (2-4 days) of fever, malaise, congestion, conjuctivitis, Koplik spots
  • maculopapular rash - starts behind the ears and on the forehead and spreads across the body
191
Q

measles in pregnancy

A

the risk is to the MOTHER

consequences:
- foetal loss (miscarriage, intra-uterine death)
- preterm delivery
- increased maternal morbidity
- no congenital abnormalities to the foetus

in susceptible pregnant women who have been in contact with suspected/confirmed measles:
- measles immunoglobulin attenuates the illness (must be given within 6 days of exposure)
- no evidence that it prevents intrauterine death or preterm delivery

192
Q

parvovirus B19 clinical presentation

A
  • erythema infectiosum (fifth disease)
  • transient aplastic crisis
  • arthralgia
  • non-immune hydrops fetalis
193
Q

parvovirus in pregnancy - treatment

A
  • intrauterine blood transfusion
  • some will resolve spontaneously
  • if the child survives the hydrops state, the long-term prognosis is quite good
194
Q

Zika virus - clinical presentation, consequences in pregnancy, congenital Zika syndrome

A

presentation:
- 80% of infections are ASYMPTOMATIC
- fever, rash, myalgia, arthralgia
- travel: mainly Caribbean and Central/South America

consequences:
- miscarriage, stillbirth, microcephaly

congenital Zika syndrome:
- severe microcephaly + skull deformity
- decreased brain tissue + seizures
- retinopathy and deafness
- talipes
- hypertonia

195
Q

structural difference between gram-positive and gram-negative organisms

A
  • gram-positives have a THICK peptidoglycan cell wall
  • gram-negatives have an outer membrane (which is part of the reason why some antibiotics don’t work on gram-negatives)
196
Q

beta-lactams

A
  • inactivate the enzymes that are involved in the terminal stages of cell wall synthesis (transpeptidases also known as penicillin binding proteins)
  • this means that the cells will have no peptide crosslinks and hence have a weak cell wall
  • beta-lactam is a structural analogue of the enzyme substrate
  • this is bactericidal
  • activate against rapidly-dividing bacteria; so no effect on bacteria that are in a stationary phase of the cell cycle
  • ineffective against bacteria that do NOT have a peptidoglycan cell wall (e.g., Mycoplasma and Chlamydia)
197
Q

is penicillin active against gram-positive or gram-negative?

A

gram-positives

198
Q

what are clavulanic acid and tazobactam?

A
  • these are both beta-lactamase inhibitors
  • they protect penicillins from breakdown by beta-lactamase
  • this increases the coverage of the antibiotics to include S. aureus, gram-negatives and anaerobes
199
Q

give 3 examples of carbapenems

A
  • meropenem
  • imipenem
  • ertapenem
200
Q

key features of beta-lactams

A
  • relatively non-toxic
  • renally excreted (so reduced dose needed if renal impairment)
  • short half-life
  • will not cross an intact blood-brain barrier
  • cross allergenic (penicillins approx. 5-10% cross-reactivity with cephalosporins and carbapenems)
201
Q

examples of glycopeptides

A
  • vancomycin
  • teicoplanin
202
Q

mechanism of action of glycopeptides

A
  • at the end of the peptidoglycan precursors there is an amino acid chain
  • the glycopeptide will bind to this amino acid chain and it prevents glycosidic bonds and peptide crosslinks
  • they are similar to beta-lactams, however, instead of binding to the enzymes themselves, they bind to the binding sites of the enzymes on the cell wall component precursors
203
Q

inhibitors of protein synthesis

A
  • aminoglycosides (gentamicin, amikacin, tobramycin)
  • tetracyclines
  • the MSL group (macrolides, lincosamides, streptogramins)
  • chloramphenicol
  • oxazolidinones (linezolid)
204
Q

aminoglycosides - examples, mechanism of action

A

gentamicin, amikacin, tobramycin

  • the full mechanism of action is not fully understood
  • they prevent elongation of the polypeptide chain
  • they cause misreading of codons along the mRNA
205
Q

tetracyclines mechanism of action

A
  • bind to ribosomal 30S subunit
  • prevent binding of aminoacyl-tRNA to the ribosomal acceptor site, thereby inhibiting protein synthesis
206
Q

macrolides

A
  • bacteriostatic
  • minimal activity against gram-negatives
  • useful for mild staphylococcal or streptococcal infections in penicillin-allergic patients
  • also active against Campylobacter spp., legionella, pneumophila
  • new agents, such as clarithromycin and erythromycin, have better pharmacological properties

mechanism of action:
- bind to the 50S subunit of the ribosome and
- interfere with translocation
- stimulate dissociation of peptidyl-tRNA

207
Q

chloramphenicol

A
  • bacteriostatic
  • broad antibacterial activity
  • rarely used (apart from eye preparations and special considerations)
  • risk of aplastic anaemia
  • caution must be taken in neonates because they have a reduced ability to metabolise the drug and they can get Grey Baby Syndrome

mechanism of action = binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation

208
Q

oxalidinones (e.g., linezolid)

A
  • binds to the 23S component of the 50S subunit to prevent the formation of a functional 70S initiation complex (which is required for translation)
  • highly active against gram-positive organisms (including MRSA and VRE)
  • NOT ACTIVE against most gram-negatives
  • disadvantages: expensive, may cause thrombocytopenia and optic neuritis
209
Q

inhibitors of DNA synthesis

A

quinolones
- ciprofloxacin
- levofloxacin
- moxifloxacin

nitroimidazoles
- metronidazole
- tinidazole

210
Q

floroquinolones

A
  • act on the alpha-subunit of DNA gyrase predominantly, with other antibacterial actions
  • bactericidal
  • broad antibacterial activity, esp. against gram-negative inc. pseudomonas aeruginosa
  • newer agents (e.g., levofloxacin, moxifloxacin) have increased activity against gram-negatives and intracellular bacteria
  • well absorbed following oral administration
  • uses: UTIs, pneumonia, atypical pneumonia, bacterial gastroenteritis
211
Q

nitroimidazoles

A

examples:
- metronidazole
- tinidazole

  • under anaerobic conditions, an active intermediate is formed, which causes DNA strand breakage
  • rapidly bactericidal
  • active against anaerobic bacteria and protozoa
  • nitrofurans (nitrofurantoin is particularly useful because it concentrates in the bladder)
212
Q

rifampicin

A

mechanism: inhibits protein synthesis by binding to DNA-dependent RNA polymerase thereby inhibiting initiation

  • bactericidal
  • active against certain bacteria, inc. Mycobacteria and Chlamydiae
  • important to monitor LFTs (metabolised by the liver)
  • beware of interactions with other drugs metabolised by the liver (e.g., warfarin, oral contraceptive)
  • side effects = may turn urine and contact lenses orange
213
Q

cell membrane toxins

A

Daptomycin
- cyclic lipopeptide
- activity limited to Gram-positive organisms
- likely to be used in treating MRSA and VRE infections as an alternative to linezolid and Synercid

Colistin
- polymyxin antibiotic
- active against gram-negative organisms inc. pseudomonas aeruginosa, acinetobacter baumanii, Klebsiella pneumoniae
- NOT absorbed orally
- nephrotoxic - should be reserved for use against multi-resistant organisms

214
Q

mechanisms of antibiotic resistance

A

1) inactivation
- beta lactams
- aminoglycosides
- chloramphenicol

2) altered target
- beta lactams
- macrolides
- quinolones
- rifampicin
- chloramphenicol
- linezolid
- glycopeptides

3) reduced accumulation
- tetracyclines
- beta lactams
- aminoglycosides
- quinolones
- chloramphenicol

4) bypass
- trimethoprim
- sulphonamides

215
Q

measures to reduce the spread of antibiotic resistance in hospital

A
  • control antibiotic usage and encourage prescribing habits
  • improve standards of hospital hygiene - encourage handwashing
216
Q

examples of misuse of antibiotics

A
  • no infection present
  • selection of incorrect drug
  • inadequate or excessive dose
  • inappropriate drug therapy
  • expensive agent used when cheaper is available
217
Q

what is the minimum inhibitory concentration (MIC)

A
  • this is the minimum drug concentration that is required to inhibit the growth of organism in a culture
  • there are regulatory bodies that set an MIC cut-off (if the MIC is higher than X the organism is resistant, if it is lower than X is it sensitive)
218
Q

agar disc diffusion method

A
  • the disc is impregnated with antibiotic which diffuses out from the disc
  • as distance from the disc increases, the concentration of the antibiotic decreases logarithmically
  • the border of the clear zone is the MIC
    (- time consuming)
219
Q

preliminary identification of organisms

A
  • gram-staining
  • send as much specimen as possible (higher volume of sample means higher sensitivity)
  • rapid antigen detection (immunofluorescence, PCR)
220
Q

antibiotics - patterns of activity

A

Type I
- concentration-dependent killing
- prolonged persistent effect
- goal: maximise concentration

Type II
- time-dependent killing
- minimal persistent effects
- goal: maximise duration of exposure

Type III
- time-dependent killing
- moderate to prolonged persistent effects
- goal: maximise amount of drug

221
Q

type I antibiotic activity

A

e.g., aminoglycosides
- peak above the MIC (Cmax) is the MOST important factor because these drugs have concentration-dependent effects
- therefore, aminoglycosides are given as one big dose once a day, to try and get the Cmax as high as possible
- the higher the Cmax the better the clinical outcome for infections treated with aminoglycosides
- however, achieving a high Cmax must be balanced with the risk of adverse effects
- with aminoglycosides, you are worried about ototoxicity and nephrotoxicity
- you also measure the trough concentration to ensure that the drug is eliminated

222
Q

type II antibiotic activity

A

e.g., penicillins
- these are time-dependent so you want to maximise the time above the MIC
- the concentration above the MIC is NOT very important
- so, with penicillins, you tend to take them frequently

223
Q

type III antibiotic activity

A

e.g., vancomycin
- sort of a combination of type I and II
- the area under curve (AUC)/amount of drug is the MOST important factor
- so, it has both concentration and time-dependent effects
- infusions can maintain an AUC above the MIC

224
Q

skin infections

A

examples:
- impetigo
- cellulitis
- wound infections

common organisms:
- staphylococcus aureus
- beta-haemolytic streptococci

treatment: flucloxacillin
(unless penicillin allergy or MRSA)

225
Q

eagle effect

A
  • relative lack of efficacy of beta-lactams on infections having large numbers of bacteria
  • penicillin works by inhibiting cell wall synthesis, but cell wall synthesis only occurs when the bacteria are dividing
  • in cases of extremely high bacterial burden, bacteria may be in the stationary phase of growth
  • in this case, as no bacteria are actively replicating, penicillin has NO activity
226
Q

antibiotics for CAP mild, CAP severe, pharyngitis, and hospital-acquired pneumonia

A

pharyngitis:
- benzylpenicillin 10 days

CAP mild:
- amoxicillin

CAP severe:
- co-amoxiclav + clarithromycin

hospital-acquired pneumonia:
- cephalosporin
- ciprofloxacin
- piperacillin/tazobactam
- if MRSA, consider adding vancomycin

227
Q

bacterial meningitis treatment

A

ceftriaxone
consider adding amoxicillin if Listeria is likely

Baby <3 months
- cefotaxime + amoxicillin (to cover Listeria)
- ceftriaxone is NOT used in neonates because it displaces bilirubin from albumin and can cause biliary sludging

Neisseria meningitidis
- benzylpenicillin (high-dose)
- ceftriaxone or cefotaxime

228
Q

UTIs treatment

A

simple cystitis
- trimethoprim 3 days

hospital-acquired UTI
- cephalexin or augmentin

infected urinary catheter
- change under gentamicin cover

229
Q

causes of immunocompromise

A

metabolic/endocrine
- alcohol abuse
- diabetes mellitus
- uraemia
- malnutrition

impaired barrier to infection
- burns
- haemodialysis
- IVDU

pregnancy

extremes of age

230
Q

classification of immunocompromise

A

Primary
- UNC93B deficiency and TLR3 deficiency (associated w herpes simplex encephalitis)
- epidermodysplasia verruciformis
- SCID
- haemophagocytic lymphohistiocytosis in perforin deficiency (perforin deficiency is also associated w an increased evidence of EBV)
- HHV8 is associated w a STIM1 mutation

Acquired
- solid organ transplantation
- bone marrow transplantation
- immunosuppressive drugs
- advanced HIV infection
NB: measles also causes prolonged immunodeficienct state after the infection

231
Q

immunosuppression - HIV infection

A
  • long incubation period
  • directly targets CD4+ T cells
  • through the loss of CD4+ T cells, you get an increase in the risk of opportunistic infections
  • early on in disease you will get a dramatic decline in CD4 count
  • then, the CD4+ count will recover but then decline more slowly
  • as CD4+ count decreases, the risk of opportunistic infection increases
232
Q

immunosuppression in transplantation

A
  • with haematological transplantation, the patient will be immunosuppressed for a while after the transplant
  • once the transplant is accepted and established, immunosuppression will be tailed off and they will return to normal
  • with solid organ transplants, the patients will be on immunosuppression for the rest of their lives
233
Q

major classes of immunosuppressive drugs

A
  • glucocorticoids or steroids
  • calcineurin inhibitors (T-cell function)
    cyclosporine
    tacrolimus
  • antiproliferative agents
    azathioprine
    mycophenolate mofetil (MMF) or mycophenolic acid (MPA)
    sirolimus
  • antibodies
    depleting
    non-depleting: anti CD-25 receptor antibodies, costimulation blockers
  • co-stimulation blockers
234
Q

factors to consider in immunosuppression

A

immunosuppressive treatment
- type, timing, intensity

prior treatment
- antimicrobial use, chemotherapy

muco-cutaneous integrity
- catheters, lines, drains

surgical complications
- collections

metabolic conditions
- uraemia, alcoholism, DM, age

viral infections
- herpes viruses, HNV, HCV, HIV, RSV, respiratory virus

235
Q

timeline of viral infections following solid organ vs bone marrow transplantation

A

solid organ:
- they do not tend to reactivate viral infections until over a month after the transplant
- early infections (<1 month) tend to be those that are transmitted from the donor
- can be controlled by adequately testing the donor

bone marrow:
- viral infections tend to occur early/within 1 month
- this is because BM transplant patients will receive intensive immunosuppression

236
Q

transplant patients - sources of infection

A

viruses acquired from the graft (e.g., HBV)
- this can be assessed via serology and risk assessment of the donor

viral reactivation from the host (e.g., HSV)
- this can be tackled by looking at the patient’s serostatus, monitoring, prophylaxis and pre-emptive therapy

novel infection from infected individual (e.g., VZV)
- isolation
- advice for family and contacts
- post-exposure prophylaxis
- vaccinating contacts

237
Q

opportunistic viral infections - herpes simplex virus (symptoms, complications, treatment)

A

symptoms:
- cold sores
- stomatitis
- mouth ulcers
- recurrent genital disease (HIV and adult transplant)

complications:
- cutaneous dissemination
- oesophagitis
- hepatitis
- viraemia

treatment:
- aciclovir or valaciclovir
- foscarnet

238
Q

opportunistic varicella zoster virus

A

manifestations:
- skin lesions
- pneumonitis
- encephalitis
- hepatitis
- purpura fulminans in the neonate
- acute retinal necrosis
- progressive outer retinal necrosis
- VZV - associated vasculopathy

shingles is usually a late manifestations of ZVZ post-transplant

shingles can be an early manifestation of HIV

multidermatomal or disseminated zoster has a HIGH mortality

prevention:
- aciclovir prophylaxis provides some protection
- post-exposure prophylaxis with VZV immunoglobulin

239
Q

opportunistic CMV

A

manifestations:
- retinitis
- encephalitis
- pneumonia
- gastroenteritis

  • pathological histological feature of CMV infection: Owl’s eye appearance of lung pneumocytes caused by inclusion bodies
  • this tends to develop within 6 months of transplantation
  • risk is dependent on whether the donor or recipient has previously had a CMV infection
240
Q

opportunistic CMV post transplant - when is the risk greatest in solid organ vs bone marrow transplant

A

solid organ transplantation:
- the greatest risk of reactivation is when the donor has had past CMV infection but the recipient is naive

bone marrow transplantation:
- the greatest risk of reactivation is when the recipient has had past CMV infection but the donor is naive

241
Q

opportunistic EBV infection post transplantation. what are you most concerned of?

A
  • development of malignancy
  • can lead to post-transplant lymphoproliferative disease (PTLD)
  • rising EBV viral load associated with widespread lymphadenopathy raises suspicion of PTLD
  • confirmed by biopsy of lymph nodes

management:
- reduce immunosuppression
- anti-CD20 monoclonal antibodies (Rituximab) - removes the B cells

242
Q

Kaposi sarcoma

A
  • associated with HHV8
  • presents with brownish/purplish vascular lesions that can be cutaneous or visceral

characteristic histological findings:
- spindle cell proliferation
- neo-angiogenesis
- inflammation and oedema

diagnosis: biopsy

treatment:
- chemotherapy
- antiretroviral therapy

243
Q

JC virus

A
  • polyomavirus
  • associated with progressive multifocal leukoencephalopathy
  • this is a dementing process that is characterised by loss of higher functions (personality change, motor deficits, focal neurological signs)
  • main pathological feature is demyelination of white matter
  • diagnosis: MRI and PCR of CSF
244
Q

BK virus

A
  • polyomavirus
  • dsDNA

can cause:
- BK cystitis (post-stem cell transplantation)
- BK nephropathy (post-renal transplant)

can be treated by reducing immunosuppression

245
Q

adenovirus (opportunistic, post transplant)

A
  • particular problem after bone marrow transplant
  • can occur as an exogenous infection or reactivation of persistent endogenous infection

manifestations:
- fever (septic appearance)
- encephalitis
- pneumonitis
- colitis

  • high mortality in disseminated infection
  • therefore, regular screening of urine, respiratory secretions, blood and stools to check for disseminated disease in post-transplant patients
246
Q

respiratory viruses in the immunocompromised

A

increased risk of complications (pneumonitis) and high mortality associated with:
- influenza A and B
- parainfluenza
- RSV
- adenovirus
- MERS

  • diagnosed by taking nasopharyngeal aspirates, bronchioalveolar lavage, nose and throat swabs
  • multiplex PCR is the investigation of choice
247
Q

human parvovirus B19 in the immunocompromised

A

cause of chronic anaemia
diagnosis:
- serology (IgM) is NOT useful in the immunocompromised
- PCR of blood

treatment: IVIG
- may require blood transfusion

248
Q

do worms tend to replicated within hosts

A

no

249
Q

traditional classification of worms (based on shape)

A

Cestodes (tape worms)
- hydratid disease
- pork/beef/fish tapeworms

Trematodes (flukes)
- less common
- can affect lung, liver or intestines
- shcistosomiasis is an example

Nematodes (roundworms)
- hookworms
- ascarids
- strongyloides

250
Q

Pork and beef tapeworms

A
  • humans are the definitive host for these tapeworms
  • within the human, the adult tapeworm will lay eggs in the GI tract
  • the eggs will be excreted in the stools
  • these will then be eaten by pigs and cows
  • within these intermediate hosts, the egg will hatch, the larvae come out, they burrow through the intestine into tissues where they form a cyst
  • the cyst will contain a small tapeworm
  • humans will then eat the beef or pork, the cysts will open, releasing the tapeworm

Types:
- Taenia solium (pigs)
- Taenia saginata (cows)

251
Q

Schistosomiasis

A

4 main species found in Africa, South-East Asia and South/Central America

Lifecycle:
- Cercariae invade human skin when in contact with contaminated water
- worms develop in the venous plexus
- eggs excreted into faeces and urine
- hatch into miracidia, which parasitise snails
- snails release cercariae

damage is caused by the laying of eggs
- migration of eggs through the bladder or bowel causes damage, increases risk of bladder cancer
- retrograde passage of eggs into the liver causes cirrhosis (however, synthetic function is preserved)

diagnosis:
- microscopy (urine, stool)
- serology
- biopsy
- response to treatment

treatment:
- praziquantel

252
Q

mosquitos diseases

A
  • malaria
  • elephantiasis
  • dengue
  • yellow fever
  • west nile virus
  • zika virus
253
Q

malaria clinical features

A

fevers - cyclical or continuous with spikes
malaria paroxysm - chills, high fever, sweats

severe malaria:
- high parasitaemia or schizont
- altered consciousness with/without seizures
- ARDS
- circulatory collapse
- metabolic acidosis
- renal failure, haemoglobinuria (blackwater fever)
- hepatic failure
- coagulopathy +/- DIC
- severe anaemia
- hypoglycaemia
- end-organ damage

254
Q

diagnosis of malaria

A

3 thick and thin blood smears
- Field’s or Giemsa stain
- thick: screen for parasites (sensitive)
- thin: identify species and quantify parasitaemia (>2% is high)

malaria antigen detection tests (rapid antigen test)
- paracheck-PF (detect plasmodial HRP-II)
- optiMAL-IT (parasite LDH)

255
Q

non-falciparum malaria treatment

A

chloroquine - 3 days
primaquine - 14 days (NB screen for G6PD)

256
Q

falciparum malaria treatment

A

mild (no vomiting, parasitaemia <2% and ambulant):
- oral malarone
- artemisin combination therapy (ACT)
- oral quinine

severe:
- ABC approach
- correct hypoglycaemia
- cautions hydration
- organ support
- IV artesunate

257
Q

dengue clinical features

A
  • fever
  • headache (retro-orbital)
  • myalgia
  • erythrodermic rash (50%)
  • bleeding
  • hepatitis
  • severe: encephalitis, myocarditis
258
Q

typhoid fever - clinical features, complications, treatment

A

clinical features:
- high prolonged fever
- headache
- rose spots (rare)
- constipation
- dry cough

incubation: 7-18 days (can be up to 60)

complications:
- GI bleed
- perforation
- encephalopathy

treatment:
- empirical ceftriaxone IV
- azithromycin PO

259
Q
A

Pathology (5 decks)

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