Immunology and Infection

Question 1

What bacteria commonly cause cellulitis?

Answer 1

Betahaemolytic streptococci cause 70-85% of infections (S dygalactiae, S pyogenes)
S. aureus less common, more likely to cause if pustules

Question 2

In what population should gram negative cellulitis be suspected?

Answer 2

Immunocompromised host
Cirrhosis
Chronic leg ulceration
Cellulitis of abdominal wall/groin

Marine exposure = Vibrio, Aeromonas

Dog or cat bites = Pasteurella multocida, Capnocytophagia canimorsus

Question 3

What are the common organisms that cause diabetic foot infections?

Answer 3

Polymicrobial
Acute infection: S. aureus and Streptococci
Chronic: gram negatives and anaerobes

Question 4

What are ESBLs, what antibiotics are they resistant to and what organisms express them?

Answer 4

Extended spectrum Beta-lactamases = plasmid mediated expression of extracellular enzyme that hydrolyses the beta-lactam molecule
Confers resistance to all penicillins 1st-3rd generation cephalosporins and aztreonam
Seen in aerobic gram negative bacilli such as E. coli and K. pneumoniae

Question 5

What antibiotics can be used in ESBL infection?

Answer 5

Sepsis: carbapenems, gentamicin or amikacin

Uncomplicated UTI: nitrofurantoin or trimethoprim if susceptible, fosfomycin, mecillinam

Question 6

What is the most common causative organism of community acquired pneumonia?

Answer 6

S. pneumoniae (approx 30%)

Question 7

What organisms need to be covered with empiric antibiotic therapy for community acquired pneumonia?

Answer 7

S pneumoniae, mycoplasma pneumoniae, S aureus, Legionella, Enterobacteriae, Haemophyllis influenzae

Question 8

What is the CURB65 score for community acquired pneumonia and how is it interpreted?

Answer 8

Mortality score where 0-1 = low risk, 2 = moderate risk and 3-5 = high risk to inform treatment decision

Confusion
Urea > 7
RR > 30
BP < 90
Age > 65

Question 9

What is the 30-day mortality for different CURB65 scores and how should they be managed?

Answer 9

0 or 1 = <3%, managed in community with PO amoxicillin

2= 9%, inpatient management with IV therapy with atypical cover (e.g. Amox + doxy)

3-5 = 15-40%, consider ICU with IV therapy including resistant organisms and atypical cover (e.g augmentin + azithromycin)

Question 10

What is the rational behind using doxycycline or macrolides (azithromycin) in CAP?

Answer 10

Provide cover for mycoplasma, chlamydophila
Macrolides also provide cover for legionella

Question 11

What is the rationale for Augementin or ceftriaxone for unwell patients with CAP?

Answer 11

Also provide cover for beta-lactamase producing bacteria such as H. influenzae whilst retaining S pneumoniae cover

Question 12

What are the 4 structural proteins of SARS-CoV2?

Answer 12

Membrane (M)
Spike glycoprotein (S) = target of vaccines
Envelope (E)
Nucleocapsid (N)

Question 13

What cells does SARS-COV2 infect and how does in gain entry into the cell?

Answer 13

Affects upper and lower respiratory tract epithelial cells
Gains access via cell surface receptors such as ACE2

Question 14

What are the targets of nirmatrelvir/ritonavir, molnupiravir and remdesivir?

Answer 14

Nirmatrelvir/ritonavir = viral protease
Remdesivir/molnupiravir = RdRP (RNA dependent RNA polymerase)

Question 15

What type of virus is SARS-CoV2?

Answer 15

Coronavirus: single stranded positive sense RNA virus

Question 16

What host immune response is recruited to SARS-CoV2 infection?

Answer 16

APCs (DCs) activate antigen specific CD4+ and CD8+ T-cells
Antigen specific B-cells are also recruited and supported by CD4+ T-cells, initially generate low affinity IgM Abs, other B-cells undergo affinity maturation and class switching in lymphoid tissues (nodes and spleen) to produce large amounts high affinity IgG antibodies

Viral clearance requires B and T cell response, T-cell response protects against severe disease (and is the desired outcome fo vaccine therapy)

Question 17

What mechanisms contribute to severe COVID?

Answer 17

Failure of interferon signalling leads to prolonged viral replication, viraemia and dysregulated hyperinflammatory response

2% men with critical COVID have X-linked recessive TLR7 deficiency

20% >80 with severe COVID have anti-IFN antibodies

Question 18

What is the key difference between omicron variant and wildtype and delta Variants of SARS-CoV2 virus?

Answer 18

Omicron has greater affinity for upper airway epithelial cells so presents more similarly to other viruses whereas others had greater affinity for lower resp tract.

Omicron less likely to result in hypoxia and hospitalisation

Question 19

What is the timeline of infection, transmissibility and antibody response to SARS-CoV2 infection?

Answer 19

Incubation 3-7 days
Viral shedding 15-18 days
Virus cleared after 30 days
IgM peak at 20 days
IgG peak at 25 days, lasting up to 4 months

Question 20

What are mRNA vaccines and their advantages and disadvantages?

Answer 20

Lipid nanoparticles containing mRNA code for an antigen which is synthesised in host cells. This then generates a host immune response to minimise the severity of future infection

Clinically only mRNA vaccine is COVID spike protein, includes anchor so not released in blood and only expressed on cell surface

Advantages:
- highly potent: small amount mRNA generates large amount of protein
- easy to manufacture

Disadvantages:
- mRNA unstable, cold chain must be -70C
- risk of pericarditis/myocarditis

Question 21

What are protein subunit vaccines, their advantages and disadvantages?

Answer 21

Protein antigen + adjuvant that illicit low grade cellular immune responses

Advantages: good safety profile

Disadvantages:
- low immunogenecity requires adjuvants, often booster doses
- lower ability to produce cellular immune response
- difficulty scaling manufacturing

Question 22

How do viral vector vaccines work, what are their advantages and disadvantages?

Answer 22

Antigen encoding DNA is packages in viral vector which carries it into host cells, where the DNA in translated and transcribed into antigen without being incorporated into host genome

Example is Astrazeneca vaccine for COVID (where chimpanzee adenovirus is used and does not generate immune response to vector)

Advantages:
- robust immune response
- stored at 2-7C

Disadvantages:
- Vaccine induced thrombotic thrombocytopenia (young women)
- Immunity can be developed to viral vector, limiting ability to give repeated doses

Question 23

What is the influence of SARS-CoV2 vaccination on previously exposed individual? What is the outcome of a booster?

Answer 23

Generates a greater and longer lasting immune response than a COVID-naive individual

Booster generates higher titre antibiodies that last longer

Question 24

What is the recommended vaccine schedule for SARS-COV2?

Answer 24

Primary course for everyone > 5 years
Booster 6 months after COVID infection or vaccine or 3 months after Evusheld
3rd booster if immunocompromised

Question 25

What are contraindications to SARS-CoV2 vaccination?

Answer 25

Anaphylaxis to previous dose of vaccine or any component, myo/pericarditis following previous dose

Question 26

How is COVID treated?

Answer 26

Vaccination = pre exposure prophylaxis No therapies for post exposure prophylaxis Mild-moderate (no hypoxia) = aim to prevent severe disease =nirmatrelvir/ritonavir or remdesivir, Inhaled budesonide 2 puffs BD for up to 14 days Severe COVID (hypoxic) = treatment to improve survival = dexamethasone, baricitinib and tocilizumab. + Remdesivir to reduce length os stay + VTE prophylaxis Critical COVID (ICU) = treatment to improve survival = dexamethasone, baricitinib and tocilizumab. + Remdesivir to reduce length os stay + VTE prophylaxis There is no role for Evusheld in current management of COVID as ineffective for later variants

Question 27

What is paxlovid, its dosage, adverse effects and contraindications?

Answer 27

Combination of Nirmatrelvir (COVID protease inhibitor) + ritonavir (CyP450/CYP3A4 inhibitor that boosts nirmatrelvir) used to treat COVID Dose: - eGFR > 60: 300 mg nirmatrelvir + 100 mg ritonvavir BD for 5 days - eGFR 30-60: 150 mg nirmatrelvir + 1 00 mg ritonavir BD for 5 days Adverse effects: headache, dygeusia, diarrhoea, vomiting Contraindications: - eGFR < 30 -Severe hepatic impairment (Chalres Pugh C) - Pregnancy - Drug interactions

Question 28

What is remdesivir, its dosage, adverse effects and contraindications?

Answer 28

Ribonucleoside analogue that inhibits RNA-dependent RNA polymerase (RdRp 3 day IV course: 200 mg day1, then 100 mg day 2+3 -> for hospitalised and pregnant women Adverse effects: - LFT derangement - renal impairment - infusion reaction Contraindications: - eGFR < 30 - Liver disease

Question 29

What is the mechanism of severe COVID and what therapies have been demonstrated to improve survival?

Answer 29

Drive by dysregulated immune response to COVID infection in which IL-6 has a central role Dexamethasone if hypoxic (use prednisolone or hydrocortisone if pregnant due to lower foetal exposure) Baricitinib Tocilizumab

Question 30

What are baricitinib and tocilizumab, when are they indicated in COVID infection and what are their contraindications?

Answer 30

Baricitinib = JAK1/2 inhibitor, given 4 mg OD for 14/7 Tocilizumab = anti-IL6 mAb Indicated for Severe/critical COVID, often used if not responding to steroid Both have been shown to reduce mortality and risk of requiring mechanical ventilation Barictinib can be used in most patients, 50% dose reduced if eGFR 30-60 Tocilizumab, weight based dosing, reserved for pregnant or if eGFR < 30 Contraindications: - sepsis or severe non-COVID infection - if already significantly immunosuppressed

Question 31

What are characteristics of human herpes viruses?

Answer 31

dsDNA genome Capsid Tegument = protein layer between nucleocapsid and envelope Glycoprotein bilayer envelope

Question 32

What are the different subfamilies of human herpes viruses, their target cells and latency?

Answer 32

Alphaherpesvirinae target mucoepithelial cells are are latent in sensory ganglia. E.g HSV1, HSV2 and VZV Betaherpesevirinae target white blood cells. E.g CMV latent in monocytes and lymphocytes, Roseolovirus latent in T-cells, leucocytes Gammaherpesvirinase target lymphocytes and are latent in B-cells. E.g. EBV and KSHV (HHV8)

Question 33

What are characteristics of CMV infection in an immunocompetent host?

Answer 33

Typically asymptomatic Fever, lymphadenopathy and lymphocytosis +/- thrombocytopenia and haemolytic anaemia Rarely pneumonitis, hepatitis, meningoencephalitis and myocarditis

Question 34

When is CMV transmission the highest in pregnancy? What are common complications

Answer 34

First trimester in primary infection IUGR, thrombocytopenia, microcephaly, chorioretinitis and sensorineural hearing loss

Question 35

How does CMV infection manifest in the immunocompromised host?

Answer 35

Rarely asymptomatic Commonly presents as flu-like illness Can occur in tissue invasion such as GI tract, hepatitis, pulmonary disease, meningoencephalitis, retinitis (in HIV esp)

Question 36

What are risk factors for CMV infection in an immunocompromised host?

Answer 36

CMV+ donor with CMV- recipient in solid organ transplant CMV- donor with CMV+ recipient in HSCT Immunomodulator therapy Hypogammaglobulinaemia

Question 37

What are indirect effects of CMV infection?

Answer 37

Cellular mediated effects such as allograft injury or rejection, EBV-associated PTLD, opporutnistic infection

Question 38

How is CMV diagnosed in the immunocompetent and immuncompromised host?

Answer 38

Immunocompetent = serology (IgM) Immuncompromsied = CMV PCR or serum or histopathology of tissue

Question 39

How is CMV infection treated?

Answer 39

1st line = IV ganciclovir or PO valganciclovir (IV if severely unwell) 2nd line = foscarnet 3rd line = cidofovir or marabivir for resistant or refractory disease

Question 40

What is the mechanism of action and adverse effects of: -Ganciclovir/valganciclovir -foscarnet -Cidofovir -Marabivir - Letermovir

Answer 40

-Ganciclovir/valganciclovir = inhibitor of CMV DNA polymerase, renally dosed, may cause neutropenia -foscarnet = pyrophosphate analgoue that directly binds to DNA ploymerase, causes nephrotoxicity, electrolyte wasting -Cidofovir = cytosine analogue, significant toxicity can be mitigated by probenecid -Marabivir = targets viral UL97 an ATP competitive kinase inhibitor, CYP450-mediated drug interaction -Letermovir binds CMV terminase complex, not to be used for treatment of CMV, does not cover other herpesviruses, interacts with ciclosporin

Question 41

What are prophylaxitic strategies for CMV prevention?

Answer 41

Prophylaxis = - valganciclovir for solid tumours - letermovir in HSCT as does not induce cytopenias

Question 42

How is EBV transmitted?

Answer 42

Mainly oral Can be transmitted via transplant, blood products and possibly in sexual fluids

Question 43

What is the immunological lifecycle of EBV?

Answer 43

Lytic infection occurs in epithelium of oropharynx where it is shed Then migrates to B-cells in local lymphoid tissues, where infected memory B-cells proliferate containing cDNA = lytic phase In immunocompetent host CD4, CD8 and NK-cells bring EBV infection under control. Small pool of memory T-cells persist

Question 44

How do EBV protein levels correlate to lytic and latent phases of infection?

Answer 44

Lytic: see BZLF1, BRLF1, DNA amplification, viral capsid Latent: EBNA, LMP and EBER = non-coding RNA

Question 45

How does EBV serology correlate with EBV infection?

Answer 45

IgM seen 0-10 weeks, peaking 3-6 weeks and then declining IgG peaks at 5-7 weeks and persists

Question 46

What is the significance of the LMP-1 gene in EBV?

Answer 46

Lowly immunogeneic and mimics CD40 to promote cell survival and proliferation Recognised as oncogene in multiple cancers (Burkitts lymphoma, Hodgkins lymphoma, PTLD, nasopharyngeal carcinoma, gastric carcinoma, oral hairy leucoplakia)

Question 47

What is the role of anti-viral therapy for EBV?

Answer 47

No established role in treatment of infection or prophylaxis

Question 48

What is PTLD and how is it managed?

Answer 48

Post transplant lymphoproliferative disease, commonly occurring during EBV infection in post transplant period Managed with reduction in immunosuppression to increase T-cell responses Can also consider cytoreductive therapy such as rituximab and low dose chemotherapy

Question 49

What type of virus is varicella zoster, how is it transmitted and what diseases does it cause?

Answer 49

dsDNA Airborne Cause chickenpox and herpes zoster

Question 50

How infectious is varicella zoster and what is the rate of infection in exposed contacts?

Answer 50

Infectious from 48hours pre rash and until 4-5 days post crusting 70-90% household contacts will become infected

Question 51

What are the clinical features and complciations of chickenpox?

Answer 51

Clinical features: - viral prodroem: fever, malaise, pharyngitis - develops itchy vesicular rash in crops over 4 days which crusts over Complications: - bacterial skin infection - encephalitis esp cerebellar ataxia - pneumonia esp adults - disseminated varicella in immunosuppressed

Question 52

How is chickenpox treated in adults?

Answer 52

Given higher rate of complications then treated: - uncomplicated = oral aciclovir/valaciclovir within 72 hours of rash - complicated = IV aciclovir Post exposure prophylaxis in pregnant woman: - varicella immunoglobulin if < 4 days - oral aciclovir if > 4 days - NEVER give varicella vaccine due to risk of congenital disease from live vaccine

Question 53

What is the natural history of varicella zoster infection?

Answer 53

Control of initial chickenpox Then latent in dorsal root ganglia Can reactivate in age as herpese zoster causing rash or neuralgia

Question 54

What are the key features of herpes zoster and how is it treated?

Answer 54

Painful, unilateral, dermatomal vesicular rash Treated with valaciclovir or aciclovir Vaccination as prevention regardless of previous chickenpox or zoster history

Question 55

What type of virus is measles, its infectivity and the vaccine coverage needed to stop transmission?

Answer 55

Measles morbillivirus = ssRNA Infectious from 4/7 prior to 4/7 after rash, infectious droplets can stay airborne for up to 2hours Attack rate = 90%, R0 12-18 Needs 95% vaccine coverage in a community to stop transmission

Question 56

What are the clinical features of measles?

Answer 56

Incubation period = 6-21 days Prodrome = 2-4 days - fever, conjunctivitis, coryza, cough - koplik spots = white spots on mucosa Exanthem phase = erythematous blanching macular rash beginning on face then descends

Question 57

What are complications of measles?

Answer 57

30% affected experience complications and 30% die in developing countries Pulmonary: - croup, pneumonia, sinusitis - bronchiectasis Neurologic: -encephalitis -subacute sclerosisng pan-encephalitis

Question 58

How is measles treated?

Answer 58

No specific treatment Vitamin A in severe measles Supportive care and treatment of secondary bacterial infection

Question 59

What conditions may be seen with encephalitis?

Answer 59

Meningitis Myelitis Radiculitis Neuritis

Question 60

What is the diagnostic criteria for encephalitis?

Answer 60

Major (essential) =Altered mental status lasting > 24 hours without other cause found Minor (>3 confirmed, > 2 probable): - fever >38 within 72 hours before or after presentation - generalised or partial seizure not attributable to pre exisiting seizure - new onset focal neurology - CSF WCC > 5 -neuroimaging suggestive of encephalitis -EEG consistent with encephalitis

Question 61

What are different causes of encephalitis?

Answer 61

Infectious: - viral = most common (enterovirus overall most common, HSV1 most common for severe) - bacterial - fungal - parasites - para/post infectious: ADEM, AHLE Non-infectious: - anti-NMDR - anti-LGI1 - anti-Caspr2 - paraneoplastic limbic

Question 62

What are common causes of infectious encephalitis in >60 years old?

Answer 62

Listeria monocytogenes HSV VZV

Question 63

What are common causes of infectious encephalitis in immunocompromised?

Answer 63

HHV6 CMV EBV Mealses VZV LCMV Toxoplasma Cryptococcus JCV BKV Bartonella

Question 64

What are common causes of infectious encephalitis in different travel locations?

Answer 64

-Asia/Pacific: JEV, dengue, malaria, TB -North America: West nile virus, lacrosse virus, neuroborreliosis, coccidiomycosis -Africa: malaria, trypanosomiasis, TB

Question 65

What are common causes of infectious encephalitis associated with animal exposure?

Answer 65

-Mosquito: aborovirus, kunjin, JEV, dengue -Ticks: Rickettsiae -Bats: rabies -Monkeys and dogs: rabies

Question 66

What are common causes of infectious encephalitis associated with rash/unvaccinated?

Answer 66

Measles Mumps VZV

Question 67

What are clinical features of HSV encephalitis?

Answer 67

Bimodal onset: early childhood or >50 Affects anterior and medial temporal lobe, inferior frontal lobe, thalamus and insular cortex Presents with headache, fever, confusion and altered behaviour CSF demonstrates raised WCC, positive for HSV (typically HSV1) with peak virus days 3-7

Question 68

What is the characteristic MRI finding of HSV encephalitis?

Answer 68

asymmetrical abnomrlaities in mesotemporal, orbitofrontal lobes and insular cortex with associated oedema May also show restricted diffusion or haemorrhage

Question 69

How is HSV encephalitis treated?

Answer 69

IV aciclovir for total 14 days

Question 70

What are clinical feature of JEV encephalitis?

Answer 70

RNA flavivirus typically affecting children 5-15 day incubation period with fever, headache, myalgia and/or rash Then develop seizures, parkinsonian features, altered consciousness, possible motor weakness 50% have raised opening pressures

Question 71

How is JEV encephalitis diagnosed and treated?

Answer 71

Diagnosed by presence of JEV IgM in serum or CSF No specific antiviral, managed with supportive care

Question 72

What is acute disseminated encephalomyelitis (ADEM)?

Answer 72

Immune mediated demyelinating disorder Features: - acute polyfocal neurological deficits - encephalopathy - neuroimaging demonstrates multifocal demyelination - rare in adults - typically monophasic (cf MS) - seen post infection or vaccination

Question 73

What is Acute haemorrhagic leuco-encephalopathy (AHLE)?

Answer 73

Considered to be severe form of ADEM More common in adults 50% have preceding infection (most commonly viruses

Question 74

What is Anti-NMDAR encephalitis and its clinical features?

Answer 74

Antibodies present in CSF against GluN1 subunit of NMDAR Associated with ovarian teratomas and HSV-encephalitis More common in woman (8:2) Median onset is 21 years old In children presents with seizures, abnormal movement, irritability In adults presents with abnormal behaviour, reduced LOC, characteristic movement disorders (facial dyskinesia, stereotyped movement disorder) 5% develop demyelinating disorder

Question 75

How is NMDAR encephalitis diagnosed and treated?

Answer 75

CSF positive for anti-NMDAR antibodies Treated with steroids, IVIg, plasma exchange, treatment of underlying tumour

Question 76

What are clinical features of anti-LGI1 encephalitis?

Answer 76

Caused by antibodies against LGI1 protein which is associated with voltage-gagted potassium channels Gradual onset, peaks in age 60s Involves temporal lobe: epilepsy, amnesia Associated with hyponatraemia, faciobrachial dystonic seizure (quick movement os unilateral face and leg) Not typically associated with tumours

Question 77

How is anti-LGI1 encephalitis diagnosed and treated?

Answer 77

Diagnosed by presence of anti-LGI1 antibodies in CSF MRI may show hippocampal T2 hyperintensity, mesial temporal sclerosis Treated with immunotherapy (IV methylprednisone, IVIg, plasma exchange)

Question 78

What are clinical features of paraneoplastic encephalitis?

Answer 78

Most commonly involves limbic structures (lateral to thalamus, between cortex + brainstem) = short term memory impairment, behavioural change, altered mental state, seizure Most commonly seen bilaterally on neuroimaging, often does not involve mesial temporal lobes

Question 79

What auto-antibodies are commonly associated with paraneoplastic autoimmune encephalitis?

Answer 79

Intracellular neuronal antigens: - antibodies to ANNA-1/Hu & ANNA-3 = SCLC -antibodies to LUZP4 =Germ cell tumours -antibodies to Ma2/Ta = testicular, lung Extracellular neuronal antigens: - antibodies to AMPAR = SCLC, thymoma - antibodies to GABABR = SCLC - antibodies to mGLUR5 = hodgkins

Question 80

How are paraneoplastic autoimmune encephalopathies treated?

Answer 80

- cancer removal - Immunotherapy (IV methylprednisone, IVIg, plasma exchange)

Question 81

What features of paraneoplastic autoimmune encephalopathies favour good outcomes?

Answer 81

Early immunotherapy Autoantibodies targeting cell-surface antigens

Question 82

What is the diagnosis of the following CSF parameters? - Opening pressure < 25 cmH20 - Cell count < 5 - Cell differential showing lymphocyte predominance, no neutrophils or RBCs - CSF: plasma glucose > 0.5 - Protein < 0.5

Answer 82

Normal

Question 83

What is the diagnosis of the following CSF parameters? - Opening pressure very high - Cell count 5 -1000 - Cell differential showing lymphocyte predominance - CSF: plasma glucose >0.5 - Protein 0.2-5.0

Answer 83

Fungal infection

Question 84

What is the diagnosis of the following CSF parameters? - Opening pressure normal to high - Cell count 5 - 1000 - Cell differential showing lymphocyte predominance - CSF: plasma glucose > 0.5 - Protein 0.5 -1

Answer 84

Viral

Question 85

What is the diagnosis of the following CSF parameters? - Opening pressure high - Cell count 100 - 50,000 - Cell differential showing neutrophil predominance - CSF: plasma glucose low <0.4 - Protein >1.0

Answer 85

Bacterial

Question 86

What is the diagnosis of the following CSF parameters? - Opening pressure high - Cell count 5 - 500 - Cell differential showing lymphocyte predominance - CSF: plasma glucose Very low < 0.3 - Protein 1.0-5

Answer 86

TB

Question 87

What are characteristics MRI findings of HSV and JEV encephalitis?

Answer 87

HSV: FLAIR hyperintensity in temporal lobes JEV; assymetrical increased signal and oedema in thalamus/basal ganglia

Question 88

What are characteristic EEG findings of HSV and anti-NMDAR encephalitis?

Answer 88

HSV: periodic lateralised epileptiform discharges Anti-NMDAR: rhythmic delta activity at 1-3Hz with superimposed Beats bursts at 20-30Hz

Question 89

How should acute encephalitis be managed?

Answer 89

Start aciclovir +/- empiric antibiotics immediately Perform LP, noting CSF PCR can be falsely negative in first 72 hours If infectious cause excluded then consider steroids while awaiting antibodies

Question 90

What sites of disease and pathogens are commonly seen in Immunoglobulin or complement deficiencies?

Answer 90

Sinuopulmonary, GI, bacteraemia, meningitis Encapsulated (S. pneumoniae, H influenzae, N meningitidis), Giardia, Cryptosporidia, Campylobacter

Question 91

What sites of disease and pathogens are commonly seen in granulocyte (neutrophil) deficiencies?

Answer 91

Recurrent skin and soft tissue infections, respiratory, Lymphadenitis Fungal (aspergillus, candida) Bacterial (pseudomonas, S aureus, S typhi, Nocardia)

Question 92

What sites of disease and pathogens are commonly seen in cell-mediated immunodeficiencies?

Answer 92

Any site Viruses (CMV, EBV, HSV) Fungal (PJP, cryptococcus, candida) Mycobacteria

Question 93

What sites of disease and pathogens are commonly seen in impaired mucocutaneous barrrier?

Answer 93

Skin, line infection, gut translocation (bacteraemia) Enteric bacteria or skin commensals Candida HSV

Question 94

What pathogens are common causes of infection in TNF-a inhibitor therapy? (infliximab, adalimumab, etanercept)

Answer 94

Hepatitis B, HSV TB, norcardia, listeria Candida, PJP

Question 95

What pathogens are common causes of infection in anti-B-cell therapy? (rituximab)

Answer 95

Hepatitis B, VZV, HSV Progressive multifocal leukoencephalopathy (PML, caused by polyomavirus JC)

Question 96

What are common causes of infection in lymphocyte depleting therapy? (Alemtuzumab = anti-CD52)

Answer 96

HSV, VZV, PML, TB, bacterial infections

Question 97

What are common causes of infection in interleukin pathway inhibitors? (Tocilizumab = anti-IL6, secukinumab = anti-IL17)

Answer 97

Increases bacterial infections

Question 98

What are common causes of infection in JAK inhibitors? (tofacitinib, baracitinib, ruxolitinib)

Answer 98

Increase risk of VZV Increase serious infections TB

Question 99

What are common causes of infection in Ibrutinib (bruton's TKI)?

Answer 99

Aspergillus, PJP, Crytpococcus Respiratory infections

Question 100

What are common causes of infection in BCR-ABL inhibitors (dasatinib, imatinib)?

Answer 100

Hepatitis B, VZV

Question 100

What are common causes of infection in Idelalisib (PI3KI)?

Answer 100

Serious infections increased PJP CMV TB

Question 101

What are common causes of infection in integrin inhibitors (Natalizumab, vedolizumab)?

Answer 101

PML Respiratory infections VZV

Question 102

What are common causes of infection in complement pathway inhibitors (eculizumab)?

Answer 102

Neisseria

Question 103

What infections could be screened for in an immunocompromised individual?

Answer 103

HIV, Hep C, Hep B, Syphilis, TB, CMV, HSV, VZV, EBV

Question 104

What is the screening test for hepatitis B and who should be prescribed prophylaxis?

Answer 104

HBsAg, anti-HBcAb, anti-HBsAb + HBV DNA if HBsAg or anti-c positive Tenofovir or entecavir should be prescribed to - those who are HbsAg+ -HSCT or those receiving rituximab with antiHBcAb+

Question 105

Who should TB be screened for, what test is used and what treatments are available?

Answer 105

Screened for those with exposures prior to starting immunosuppresive therapy With Quantiferon or Mantoux If positive then then to rule out active TB Treatment dictated by drug interactions and risk of hepatoxicity

Question 106

What vaccines are contraindicated in immunocompromised patients?

Answer 106

Live vaccines MMR, oral polio, varicella, zoster, yellow fever, rotavirus

Question 107

What are common organisms that cause infection in neutropenic fevers?

Answer 107

74% Gram negative: - E coli (most common of gram-) - Enterobacter cloacae - Klebsiella - Pseudomonas - Acinetobacter (least common of gram-) 19% gram positive: - Strep > enterococcus > S aureus Rarer: anaerobes, polymicrobial, fungal

Question 108

What is antibiotics should be used in febrile neutropenia?

Answer 108

Cefepime OR piperacillin tazabactam + gentamicin if shocked + vancomycin if MRSA colonised or clinical line infection

Question 109

What is the mechanism of action of amphotericin?

Answer 109

Binds to ergosterol to affect fungal cell membrane production

Question 110

What is the mechanism of action of azole anti-fungals?

Answer 110

Affect ergosterol synthesis of cell wall via CYP3A4 inhibition

Question 111

What infections is fluconazole effective for?

Answer 111

Candida, cryptococcus, including CNS penetration

Question 112

What infections is voriconazole indicated for? What special considerations are required?

Answer 112

Covers candida and moulds Cannot be given in ESRF Due to CYP3A4 polymorphisms requires therapeutic drug monitoring

Question 113

What infections is posaconazole indicated for?

Answer 113

Prophylaxis for candida and moulds

Question 114

What infections is isavuconazole indicated for?

Answer 114

Candida, asperigillus, zygomycosis

Question 115

What is the mechanism of echioncandin anti fungals (Caspofungin)?

Answer 115

Inhibit cell wall synthesis via inhibition of glucan synthase

Question 116

What infections are echioncandin anti fungals (Caspofungin) indicated for?

Answer 116

Invasive candida infections as fungicidal against candida

Question 117

What infections is amphotericin B indicated for?

Answer 117

Any fungal infection as broadest anti-fungal activity

Question 118

How is an invasive aspergillus infection diagnosed?

Answer 118

-Suggestive radiology (chest, sinus, brain) - identification from tissue or respiratory sample in culture or histology - galactomannan antigen in serum or BAL

Question 119

How is aspergillus treated?

Answer 119

- Surgical source control - 6-12 weeks of voriconazole or isavuconazole or amphotericin - followed by secondary prophylaxis (posaconazole)

Question 120

What is zygomycosis, how is it diagnosed and treated?

Answer 120

Invasive fungal infection due to mucorales species typically affecting lungs or sinus/brain Diagnosed by microscopy, culture or histology Treated surgically + amphotericin

Question 121

In what solid organ transplants is mould/yeast cover routinely given?

Answer 121

Lung and liver

Question 122

In what solid organ transplants is toxoplasmosis cover routinely given?

Answer 122

Heart > Lung (co-trimoxazole)

Question 123

In what solid organ transplants is HBV prophylaxis given?

Answer 123

In those with HBV positive donor or recipients

Question 124

How should strongyloides infection be treated in solid organ transplant?

Answer 124

Ivermectin for Days 1+ 2 +14 to cover all laval forms

Question 125

What type of virus is human monkeypox and how is it transmitted?

Answer 125

Orthpoxvirus = brick-like virions Zoonotic infection, sexual activity MSM

Question 126

What are clinical features of monkeypox?

Answer 126

Fever, rash, lymphadenopathy Incubation period = 4-21 days Prodrome for 5 days

Question 127

How is monkeypox diagnosed and treated?

Answer 127

PCR testing of lesions Serology can support diagnosis (IgM) No anti-virals licensed Pre and post exposure vaccines in Australia

Question 128

What type of virus is Japanese encephalitis virus (JEV) and how is it transmitted?

Answer 128

ssRNA Mosquitos

Question 129

What are clinical features of JEV, how is it diagnosed and treated?

Answer 129

Most asymptomatic Otherwise non-specific viral illness followed by altered mental state and neuro deficits Serum or CSF IgM, rarely detect virus MRI changes in thalamus, basal ganglia, midbrain, pons and medulla Treatment is supportive

Question 130

What vaccines are available for JEV and who are they offered to (in Australia)?

Answer 130

Single dose live vaccine = Imojev, or 2 dose inactivated vaccine = JEspect People exposed to piggeries or pork abattoir People who work with mosquitos Lab workers who may be exposed

Question 131

What bacteria are AMP-C inducers? What antibiotics should we use for these organisms and why?

Answer 131

HECKYes (replaces ESCAPPM) Halfnia alvei Enterobacter cloacae Citrobacter freundii Klebsiella aerogenese Yersinia enterolitica Cefepime and meropenem as both weak inducers and poor substrates of AMP-C

Question 132

What is the shortened 4-month regimen for TB and what evidence supports this?

Answer 132

8 weeks rifapentine + isoniazid + pyrazinamide + moxifloxacin the 9 weeks rifapentine + isoniazid + moxifloxacin

Question 133

What are the definitions of MDR-TB, pre-XDR-TB and XDR-TB?

Answer 133

MDR-TB = resistant to isoniazid + rifampicin Pre-XDR-TB = MDR + fluroquinolones resistant XDR-TB = MDR + fluroquinolones resistant + resistant to Bedaquiline or linezolid

Question 134

What are key features of the 3 types of innate lymphoid cells and what disease processes are they indicated in?

Answer 134

None have antigen receptors - respond to cytokines ILC 1: express Tbet, respond to viral infections and produce IFNg and TNF, may drive IBD, RA ILC2: express GATA3,respond to parasitic infection, produce Th2 cytokines and may drive allergy/asthma ILC3: express RORgt, respond to bacterial infection, produce IL-17 and IL-22, and may have a role in IBD, MS, psoriasis

Question 135

What are components of neutrophil NETs?

Answer 135

-Citrullination of histone by enzyme PAD4 - Neutrophil serine protease - myeloperoxidase and phagocyte oxidase

Question 136

What are the 2 NF-kB pathways?

Answer 136

Canonical (classical) activated by PAMPs/DAMPs Non-canonical (alternative) activated by TNFR superfamily

Question 137

What is the difference between cytokines and chemokines?

Answer 137

Cytokines direct growth, maturation and activation of immune cells Chemokines direct the movement of WBC

Question 138

What are type 1 and type 2 interferons?

Answer 138

Type 1 = IFNa and IFNb Type 2 - IFNg

Question 139

What are the major acute innate cytokines?

Answer 139

IL-1, TNFa, IL-6, Il-12, CXCL8, G-CSF, GM-CSF

Question 140

What is the effect of glucocorticoids on cytokines?

Answer 140

- Target transcription factors to reduce transcription of inflammatory cytokines - attenuate TNFa and IL1B - reduce circulating T-cells and inhinit IL-2 - attenuate monocyte IL-12 resulting in shift towards Th2

Question 141

What diseases are TNFa targeted therapies used in and what are examples?

Answer 141

RA, ankylosing spondylitis, psoriasis, JIA, IBD mAbs: infiximab, adalimumab, golimumab, centolizumab Entancercept = recombinant TNFR fused to IgG Fc

Question 142

What diseases are Il-1 targeted therapies used in and what are examples?

Answer 142

RA, cryoporin associated periodic syndromes Anakinra = recombinant IL-1RA Canakinumab = mAb against IL-1B

Question 143

What diseases are IL-6 targeted therapies used in and what are examples?

Answer 143

RA, juvenile RA, castelman's disease, giant cell arteritis, cytokine release syndrome, COVID-19 IL-6R mAb: tocilizumab, sarilumab Chimeric IL-6 mAb: siltuximab Humanised IL-6 mAb: sirukumab

Question 144

What diseases are Il-17A targeted therapies used in and what are examples?

Answer 144

Psoriasis, psoriatic arhtropathy, ankylosing spondylitis IL-17A mAb: secukinumab, ixetizumab

Question 145

What diseases are Il-12/IL-23targeted therapies used in and what are examples?

Answer 145

Psoriasis, psoriatic arthropathy, IBD p40 mAbs; ustekinumab, guselkumab IgG1k mAb: tidrakizumab, risankizumab

Question 146

What diseases are IL-2 targeted therapies used in and what are examples?

Answer 146

Transplant rejection, acute GVHD IL-2Rc mAb = basiliximab

Question 147

What diseases are IL-10 targeted therapies used in and what are examples?

Answer 147

Psoriasis IL-10 administration

Question 148

What diseases are IL-4/IL-13 targeted therapies used in and what are examples?

Answer 148

Atopic dermatitis, asthma, chronic rhinosinusitis IL-4R mAb: dupilumab

Question 149

What diseases are IL-5 targeted therapies used in and what are examples?

Answer 149

Asthma, eosinophilic granulomatosis with polyangitis, hypereosinophilic syndromes Humanized IL-5 mAb: mepolizumab IL-5R mAb: benralizumab

Question 150

What is tofacitinib and what disease is it used in?

Answer 150

JAK1 + JAK2 inhibitor Used in RA

Question 151

What are the inheritance patterns of SCID?

Answer 151

X-linked Autosomal recessive

Question 152

What is the most common type of primary immunodeficiency?

Answer 152

Antibody disorders CVID is most common

Question 153

What is common variable immune deficiency? How is it diagnosed?

Answer 153

Collection of genetically heterogenous cause of hypogammaglobulinaemia resulting in recurrent infections Diagnosed by severely reduced IgG +/- low IgA and/or low IgM Confirmed by absence of antibody response to vaccination Need to exclude other causes for hypogammaglobulinaemia

Question 154

How is CVID treated?

Answer 154

Immunoglobulin replacement

Question 155

When should an immunodeficiency be suspected?

Answer 155

Severe infections Unusual infections Persistent infections (warts, diarrhoea, chronic candida) Recurrent infections (sino-pulmonary, herpes, HPV) Malignancies (rare, multiple) Autoimmune disease (atypical presentation) Not gaining weight

Question 156

Which recurrent infections are associated with which immune compartment deficiencies?

Answer 156

Bacterial = antibody Fungal/viral/HPV = T-cell Staphylococcal/fungal = phagocytic Encapsulated organisms (Streptococcus agalactiae, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Escherichia coli, Salmonella species, Klebsiella, and Pseudomonas aeruginos) = complement, spleen

Question 157

How to antibodies protect against infection from encapsulated organisms?

Answer 157

- opsonisation: IgG binding to micro-organism surface triggers phagocytosis by neutrophils and macroophages - complement activation via Ab/Ag complex

Question 158

What investigations are used to assess humoral immunity?

Answer 158

- Serum IgG, IgA, IgM +/- IgE levels +/- IgG subclasses - lymphocyte count and subsets -rule out secondary causes of low IgG - serum and urine protein + albumin (low IgG +/- IgA but preserved IgM in GIT or renal losses) - haematologic malignancy - assess antibody function 4 weeks post vaccination, normal >1 g/L or 4x increase Can also test specific antibody responses, lymphocyte proliferation and bone marrow aspirates

Question 159

How is chronic granulomatous disease treated?

Answer 159

-Co trimoxazole and itraconazole prophylaxis - IFNg (often poorly tolerated) - anakinara for colitis - HSCT

Question 160

How is the complement pathway assessed?

Answer 160

- measurement of C3/C4 - measurement of specific complement factor - measurement of regulation proteins (C1 inhibitor, factor H, factor I) - haemolytic/ELISA assays (functional MAC)

Question 161

Which complement defects are associated with which infections/autoimmunity?

Answer 161

SLE = C1, C4 and C2 (failure to clear self antigen) Recurrent sinopulmonary. = C2 Recurrent or severe infections = C3 Neisseria meningitidis, sepsis, gonococcal arthritis = C5-C9 Neisseria and bacterial = factor B, properdin and factor D

Question 162

What are the 3 ways of activating the complement pathway and which factors are involved?

Answer 162

1. Classical: Ab-Ag complexes, typically on pathogen surface, recruit C1g, C1r, C1s, C4, C2 2. MB-lectin pathway: mannose binding lectin binds mannose on pathogen surface, recruits MBL, MASP-1, MASP-2, C4 and C2 3. Alternate pathway: pathogen surface recruits C3, factor B and Factor D All result in C3 convertase

Question 163

What are the late events of the complement pathway?

Answer 163

C3 convertase leads to: - C3a and C5a: peptide mediators of inflamation and phagocyte recruitment - C3b 1. binds complement receptors on phagocytes resulting in opsonosation of pathogens and removal of immune complexes 2. Activates terminal complement components (C5b, C6, C7, C8, C9) resulting in MAC which lyse pathogens and cells

Question 164

How are complement deficiencies managed in general?

Answer 164

Vaccinations for encapsulated organisms (meningococcus, haemophilus, pneumpcoccus)

Question 165

What clinical features suggest an antibody or combined immune defect?

Answer 165

- Infection in mucosal sites (sinuses, lungs, GIT) - Bugs: strep pneumoniae, haemophilus influenzae, giardia, enterovirus, campylobacter, salmonella, shigella - autoimmune cytopenias - chronic diarrhoea

Question 166

What are the underlying mechanisms of CHAI and LATAIE?

Answer 166

CHAI = CTLA-4 haplo-insufficinecy autoimmunity and immunodeficiency = loss of function in CTLA-4 LATAIE = LRBA deficiency with autoantibodies, regulatory T (Treg) cell defects, autoimmune infiltration, and enteropathy = loss of function in LRBA (chaperone molecule which allows CTLA-4 to be moved to cell surface)

Question 167

What is the treatment for CTLA-4 deficiencies?

Answer 167

Abatercept = huCTLA-4 linked to modified Fc of IgG

Question 168

What is the inheritance pattern and clinical features of Autoimmune lyphoproliferative syndrome (ALPS)?

Answer 168

AD Lymphadenopathy, splenomegaly, autoimmune haemolytic anaemia/thrombocytopenia, high risk lymphoma Flow analysis: inceased double negative AB T-cells (up to 40%)

Question 169

What is the inheritance pattern and clinical features of Immune dyregulation polyendocrinopathy enteropathy X-linked (IPEX)?

Answer 169

X-linked Defect in FoxP3 resulting Treg deficiency Severe early onset autoimmune enteropathy, T1Dm, eczema, hypothyroidism

Question 170

What is the inheritance pattern and clinical features of Autoimmune polyendocrinopathy cadidiasis ectodermal dysplasia?

Answer 170

Defect in AIRE gene, results in inceased expression of self antigens Autosomal recessive Hypoparathyroidism, Addison's disease, chronic mucocutaneous candidiasis, other autoantibodies

Question 171

What are features of Wiskott-Aldrich syndrome?

Answer 171

X-linked defect in WASP gene Triad of eczema, thrombocytopenia, immune dysfunction

Question 172

What is the underlying genetic basis of Ataxia -telangiectasia?

Answer 172

Defect in ATM gene affecting DNA repair

Question 173

What infectious susceptibilities are the following innate immunity defects associated with? - TLR3 deficiency - CARD9 deficiency - MSMD - GATA2

Answer 173

-TLR3 = herpes simplex encephalitis - CARD9 = invasive fungal disease - MSMD = mendelian susceptibility to mycobacterial disease (IL-12/IL-13rb1 deficiency, STAT1 deficiency, IFNGR and IFNG autoantibodies) - GATA2 = Monocytopenia + disseminated MAC

Question 174

What is the most common cause of lower limb purpura?

Answer 174

Leucoclastic (hypersensitivity vasculitis secondary to furosemide, antibiotics or allopurinol Distinguished from systemic vasculitis by the presence of haematuria

Question 175

A high level of ANCA directed against PR3 or MPO is associated with which vasculititides?

Answer 175

GPA or MPA

Question 176

How quickly should someone with vasculitis respond to treatment?

Answer 176

Within days

Question 177

How long should patients treated cyclophosphamide receive haematuria monitoring?

Answer 177

Lifelong

Question 178

Which ANCA subset is associated with frequent relapse?

Answer 178

PR3-ANCA

Question 179

What are causes of raised ANCA that are not vasculitis?

Answer 179

ILD Bronchiectasis Cystic fibrosis IBD PSC Drug-induced Lupus Anti-thyroid drugs (can also cause vasculitis)

Question 180

What are the characteristics, causes and treatment of hypersensitivity (leucoclastic) vasculitis?

Answer 180

3 out of 5 of: - Age > 16 - Temporal relationship with drug - maculopapular rash - skin biopsy demonstrating perivascular neutrophils NO SYSTEMIC FEATURES Commonly caused by : - sulfonamides (frusemide, thiazide) - penicillins - cephalosporins - allopurinol - phenytoin Treated by drug cessation

Question 181

What are clinical features of microscopic polyangitis?

Answer 181

Palpable purpura + glomerualr haematuria + renal impairment +/- abnormal liver function p-ANCA with MPO specificitty

Question 182

What clinical features are suggestive of vasculitis?

Answer 182

- palpable purpura - multi-organ disease with systemic features - pulmonary-renal disease - mononeuritis multiplex (only other cause is diabetes)

Question 183

What are the 3 types of small vessel vasculitis?

Answer 183

Granulomatous polyangiitis (GPA) Microscopic polyangiitis (MPA) Eosinophilic granulomatous polyangiitis (EGPA)

Question 184

When should PR3- and MPO- ANCA be tested directly?

Answer 184

Only if small vessel vasculitis is suspected (no role in monitoring)

Question 185

What is the Chapel Hill calssification for vasculitis?

Answer 185

Based on vessel size - cannot classify all vasculitidies Large vessel = GCA, takayasu Medium vessel = polyarteritis nodosa, Kawasaki disease, isolated CNS vasculitis Small vessel 1. ANCA-associated = no immune complexes = MPA, EGPA, GPA 2. Immune-complex: Cryoglobulinaemic vasculitis IgA vasculitis (henloch-schonlein) Hypocomplementemic urticarial vasculitis (Anti-C1q) Anti-GBM

Question 186

What is Behcet's disease and how is it treated?

Answer 186

Autoinflammatory disease of arteries and vein of all sizes Associated with Turkish population Need apthous ulcers x 3 in 12 months PLUS 2/4 of: - occular inflammation - genital ulcers - pathergy reaction - skin lesions: pustules, erythema nodosum Rx: colchicine, steroids, consider VTE prophylaxis

Question 187

What are the diagnositic features of Takayasu arteritis?

Answer 187

3/6 of: - age < 40 - caludication of extremities - decreased pulsation in one or both brachial arteries - SBP difference >10 between arms - bruit over 1 or both subclavian arteries or abdominal aorta

Question 188

What are the diagnostic criteria of GCA?

Answer 188

Age at onset > 50 No systemic involvement including eyes 3 of 11: - localised headache of new onset - sudden onset visual change - PMR (2 pt) - jaw claudication - tender or decreased pulse of temporal artery (2 pt) - ESR > 50 - biopsy with necrotising arteritis (2 pt) - unexplained fever, anaemia

Question 189

How is GCA managed?

Answer 189

2 years of steroids 40-60 mg (start pre biopsy) Low dose aspirin

Question 190

What are clinical features of polyarteritis nodosa?

Answer 190

Affects medium sized vessels esp visceral Common at bifurcations and microanuerysms Can result in infarction of spleen, bowel, kidney Associated with peripheral neuropathy and HepB ANCA negative (in overlap syndorme with MPA ANCA is positive) Often good response to steroids, relapse uncommon Not associated with GN, lung haemorrhage or fever

Question 191

What is PAN associated ADA2 deficiency and how is it treated?

Answer 191

Vascultis associated with single gene mutation in ADA2, AR inheritance Milder phenotype of polyateritis nodosa Treated with anti-TNF agents, HSCT

Question 192

What are clinical features of kawasaki disease?

Answer 192

Childhood onset with fever > 5days and 4/5 of: - bilateral conjunctival injection - oromucosal changes - erythema of soles, desquatmation - polymorphous rash - cervical lymphadenopathy

Question 193

What small vessel vasculitides are ANCA positive?

Answer 193

EGPA (50% p-ANCA positive with MPO specificity) GPA MPA Some drug-induced Some rheumatoid vasculitis

Question 194

Which vasculitides are ANCA negative?

Answer 194

Polyarteritis nodosa Kawasaki disease Isolated CNS vasculitis Henoch schonlein purpura Cryoglobulinaemic vasculitis Hypersensitivity/leucoclastic vasculitis Viral vasculitis

Question 195

How is ANCA tested and what is its role?

Answer 195

- screen with indirect immunofluorescence - if screen positive then tested for PR3- and MPO- ANCA Used for diagnosing or excluding small vessel vasculitis

Question 196

What is C-ANCA?

Answer 196

Cytoplasmic granular fluorescence with central attenuation on immunofluorescence Directed against PR3, common in upper resp tract disease Typical pattern common in EGPA (90%), MPA (30%) Atypical pattern seen in autoantibodies against bactericidal permeability-increasing protein, common in pseudomonas colonised CF

Question 197

What is p-ANCA?

Answer 197

Immunofluorescence of peri-nuclear with nuclear extension Directed against MPO = GN, haematuria MPA (70%), GPA (10%) Note atypical p-ANCA is directed against other antigens and seen in IBD

Question 198

What is the pathogenesis of ANCA-associated disease?

Answer 198

Infections induce neutrophils to express ANCA antigens on surface PMNs activated by binding of self ANCA FAb and Fc to FcgR PMN degranulates (recruit complement) and release NETs (thrombotic), PR3 and MPO bind and activate endothelium ANCA also induce granuloma via monocyte acgtivation ANCA prevent A1AT mopping up PR3

Question 199

What other autoantibodies can be present in GPA and MPA?

Answer 199

ANA (15%) Lupus anticoagulant (10%) Anticardiolipin (10%) AntiGM (5%)

Question 200

How is limited GPA distinguished from generalised GPA?

Answer 200

Do not affect kidneys, but often progress to generalised

Question 201

What A1AT genotypes are associated with developing GPA? Which genotype is the most severe

Answer 201

MS, MZ, SS and ZZ genotypes All result in uninhibited PR3 which is more immunogenic Z genotype most severe + most organs involved + more progressive, has least A1AT so more PR3

Question 202

What are clinical features of GPA?

Answer 202

Conjunctival injection Urinary casts Alveolar haemorrhage Air bronchograms Cavitation Segmental necrotising GN OR pauci-immune GN

Question 203

How is ANCA vasculitis treated?

Answer 203

-induction = Corticosteroids + cyclophosphamide (oral equivalent to IV) - Maintenance = azathioprine Can also use methotrexate or azathioprine for induction

Question 204

When is rituximab used in vasculitis?

Answer 204

Poorly controlled ANCA- vasculitis

Question 205

What are features of primary pauci immune necrotising GN?

Answer 205

Common in elderly GN only, nil systemic P-ANCA positive

Question 206

What are features of MPA/PAN overlap syndrome?

Answer 206

GN, p-ANCA positive Often associated with bowel infarction or peripheral neuropathy

Question 207

How are the side effects of treatment for vasculitis minimised?

Answer 207

Immunosupressants: - shortest possible course - oral cyclophosphamide in the morning - fertility preservation (zoladex, gamete harvest, IVF) - minimise sun exposure in azathioprine Infections: - co-trimoxazole 2x/week as prophylaxis - pentamidine Q6 weekly for pneumocystis Steroids: - PPI cover - bone protection

Question 208

Through what mechanism can PTU cause ANCA associated vasculitis?

Answer 208

PTU accumulated in neutrophils and binds MPO, resulting in a change to its structure and reduced clearance

Question 209

How is drug induced vasculitis treated?

Answer 209

Mild = withdraw agent, monitor and steroids for symptom relief Multi-organ disease: steroids +/- immunosuppression, surveillance for underlying vasculitis

Question 210

What are clinical features of EGPA?

Answer 210

Asthma, pulmonary opacities, eosinophilia Affects skin, nerves, heart, bowel, kidneys 50% p-ANCA positive (MPO)

Question 211

What are the definitions of hypersensitivity and allergy?

Answer 211

Hypersensitivity = objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects Allergy = hypersensitivity reaction initiated by immunologic mechanisms

Question 212

What are the two broad types of Allergic hypersensitivity?

Answer 212

1. IgE mediated - Atopic - Non atopic (insect venom, drugs, other) 2. Non IgE mediated - T-cell - Eosinophil - IgG mediated - other

Question 213

What is atopy?

Answer 213

Immunological reaction where IgE is readily produced in response to ordinary exposure (skin, ingestion, inhalation) to common allergens of subjects environment Not all atopy is an allergic disease state, not all IgE -mediated disease is atopy

Question 214

What are the 4 main types of atopic diseases?

Answer 214

Asthma Allergic rhinits Atopic eczema Food allergy

Question 215

What are the two processes in the allergic inflammatory response?

Answer 215

1. Sensitisation - allergen is processed and presented on MHCII to Th cells - results in IgE class switching and production by B-cells/plasma cells - IgE binds tissue mast cells 2. Challenge - re-exposure to allergen with IgE mediated activation of Mast cells - release of immediate vasoactive amines and lipids - recruitment of chronic inflammatory cells

Question 216

What are the key cytokines, target cells and host defenses involved in the 4 classes of CD4+ T-cells?

Answer 216

Th1: IFNg, macrophages, intracellular pathogens Th2: IL-4, IL-5, IL-13, eosinophils, parasites Th17: IL-17, IL-22, neutrophils, extracellular pthaogens TFh: IL-21, B-cells, extracellular pathogens

Question 217

What are the physiological roles of Th2 cells?

Answer 217

Tissue homeostasis and repair Barrier immunity: elimination of microbes at epithelial barriers

Question 218

What are characteristics of IgE?

Answer 218

- 2 light + 2 heavy chains - Fc attaches to receptor on effector cells - Fab binds allergen - short serum half life approx 2 days - rapidly binds receptors on inflammatory cells (majority of IgE is bound to cells)

Question 219

How does IgE activate Mast cells?

Answer 219

Via cross-linking of 2 or more adjacent IgE molecules on FcRI

Question 220

What Mast cell mediators are released on Mast cell activation?

Answer 220

Preformed: - histamine - heparin - tryptase - chymase Synthesise: - prostaglandins - leukotrienes - cytokine: IL-4 + IL-13 (IgE class switching), IL-5 + GM-CSF (eosinophil recruitment), TNFa

Question 221

What cytokines are involved in eosinophil development?

Answer 221

IL-3 for initial commitment IL-5 and GM-CSF for maturation and priming

Question 222

What mechanisms are implicated in successful allergen immunotherapy?

Answer 222

Generate CD4+CD25+ Tregs producing IL-10 and TGF-b, which promote IgG and IgG4 production by B-cells, where IgG inhibits IgE-Allergen binding (by competing for allergen biding)

Question 223

What immune cells and factors result in allergy?

Answer 223

APC presents allergen to Th2 cell, produces: - IL-4 which promotes IgE - IL-5 which recruits eosinophils

Question 224

What are the 3 stages of allergen specific immunotherapy?

Answer 224

1. Hours to days: basophil and mast cell desensitisation 2. Days to weeks: increased Tregs 3. Weeks to months/years: regulation of B-cells and antibodies

Question 225

How long does it take to generate long term tolerance to an allergen with immunotherapy?

Answer 225

3 years

Question 226

What are the two major types of asthma and their key features?

Answer 226

T2 high: -Mast cells, Th2, NKT, ILC2s promoting eosinophils and/or IgE T2 low: - neutrophils, ILC1/3, Th1, Th17 resulting in low IgE and no eosinophils

Question 227

What are the two major types of adverse drug reaction?

Answer 227

1. Type A = pharmacological (80%) - side effects - toxicity - secondary indirect effects - drug interactions 2. Type B = hypersensitivity (10-15%) - immune mediated = allergic (5-10%) - Non immune mediated = non allergic (5-10%)

Question 228

What are the different mechanisms of immune mediated drug reactions and their characeteristics?

Answer 228

IgE mediated (<10%): - immediate (< 1 hour) - urticaria, angioedema, bronchospasm, anaphylaxis T-cell mediated (most common): - non immediate (> 1 hour) - Maculopapular, morbilliform, SJS Others: - immune complex - cytotoxic

Question 229

What are key features of an allergic drug hypersensitivity?

Answer 229

- cannot occur on first exposure (need previous exposure for sensitisation) - usually occur on first dose of subsequent course - features of IgE mediated or T-cell mediated reaction

Question 230

Which drugs can anaphylaxis independent of IgE?

Answer 230

Immunologic: - Radio-contrast - NSAIDs - dextrans (iron) - mAbs Non immunologic: - physical - ethanol - opioids

Question 231

What are the different types of immune hypersensitivity, their reactants and effector cells?

Answer 231

Type I: - IgE - Mast cell - asthma, anaphylaxis Type II: - IgG - FcR+ cells (phagocytes, NK cells) - Eg haemolytic anaemia, thrombocytopenia Type III: - IgG - FcR+ cells, complement - serum sickness Type IVa: - IFNg, TNFa (Th1) - macrophages - tuberculin reaction, contact dermatitis Type IVb: - IL-5, IL-4/IL-13 (Th2) - eosinophils - chronic asthma Type IVc: - Perforin/granzyme B (CTL) - T-cells - contact dermatitis, hepatitis Type IVd: - CXCL8, GM-CSF - Neutrophils - AGEP, behcet's

Question 232

What is the mechanism of reaction assessed for with skin testing?

Answer 232

IgE mediated reactions

Question 233

What is the mechanism of action of immediate hypersensitivity to beta lactams?

Answer 233

Antibody against beta lactam ring (note can also have antibody against side chain)

Question 234

What are the 3 mechanisms of delayed hypersensitivity to drugs?

Answer 234

TCR binding to - hapten = protein or peptide linked to active part of drug - prohapten = metabolised drug is binds to proteins - direct binding of drug to TCR (p-i concept, pharmacological interaction)

Question 235

What is the underlying immune reactions in: - amoxil bullous rash - Maculopapular exanthem - Acute generalised exanthematous pustulosis (AGEP)

Answer 235

amoxil bullous rash - CD8+T-cells direct killing keratinocytes Maculopapular exanthem - CD4+ secrete IL-5 and TNFa to kill MHCII+ keratinocytes AGEP - CD4 and CD8 activity via GM-CSF and IL-8

Question 236

How should drug allergies be managed?

Answer 236

1. Low probability = re challenge to eliminate suspicion 2. Immediate probability - avoid drug if non essential - if testing negative or unavailable re-challenge, if positive challenge the desensitise, if negative challenge then use - if testing positive then desensitise 3. High probability - avoid drug if non essential or severe reaction (SJS) - if essential but non-severe reaction then desensitise

Question 237

What are the different mechanisms of anaphylaxis?

Answer 237

1. Allergic: - IgE, FceRI mediated - Other: blood products, immune aggregates, drugs 2. Idiopathic 3. Non-allergic: - physical: exercise, cold - Other: drugs

Question 238

What is the clinical definitions of anaphylaxis?

Answer 238

1. Skin symptoms or swollen lips AND 1 of: - difficulty breathing - low BP (SBP <100 or 30% decrease) 2. Exposure to suspected allergen AND 2 of: - skin symptoms or swollen lips - difficulty breathing - reduced BP - GI symptoms 3. Exposure to known allergen with low BP

Question 239

How is anaphylaxis managed?

Answer 239

0.5 mg IM adrenaline (0.5 mL 1:1000) Oxygen Fluid resuscitation

Question 240

What is the most specific test for anaphylaxis?

Answer 240

Serum tryptase taken within 2 hours of event

Question 241

What is the most common cause of gastroenteritis?

Answer 241

Norovirus

Question 242

What GI pathogens are associated with the following foods: - Beef - Pork - Shellfish - unpasteurised dairy

Answer 242

- Beef: STEC, C. perfringens - Pork: Yersinia - Shellfish: Vibrio parahaemolyticus, norovirus - unpasteurised dairy: non-typhoidal salmonella, Campylobacter, Yersinia, S. aureus endotoxin

Question 243

What organisms that cause diarrhoea are associated with the following: - reactive arthritis - Guillain-Barre syndrome - Haemolytic uraemic syndrome - Aortitis - Liver abscess

Answer 243

- reactive arthritis: campylobacter, salmonella, shigella, yersinia - Guillain-Barre syndrome: campylobacter - Haemolytic uraemic syndrome: shiga-toxin producing E coli (STEC) - Aortitis: salmonella - Liver abscess: entamoeba histolytica

Question 244

How are giardia and entamoeba histolytica diarrhoea treated?

Answer 244

Metronidazole (+ paromomycin for entamoeba)

Question 245

How is norovirus spread?

Answer 245

Faecal-oral, droplets, fomites, cotaminated environment

Question 246

What is the duration of antibiotics for joint infections?

Answer 246

- small joints of the hand = 2/52 - large joint = 4-6/52 - prosthesis = 6/52 minimum

Question 247

According to the PIANO study, what are organisms that cause early and late prosthetic joint infections?

Answer 247

Early = gram negative (E coli) and enterococci Late = S. aureus, beta haemolytic strep

Question 248

What process gives rise to winter influenza epidemics?

Answer 248

Antigenic drift of haemagglutinin (is key mediator of immunity)

Question 249

What process gives rise to influenza A pandemics?

Answer 249

Antigenic shift = abrupt change in neuraminidase or haemagglutinin (Flu B can't because there is only one type of haemagglutinin and one type of neuraminidase)

Question 250

What is the mechanism of action of oseltamivir?

Answer 250

Neuraminidase inhibitor, prevents viral particle budding

Question 251

What is the most common cause of fever in returned traveller from: - subsaharan africa - south east asia - latin america - south central asia

Answer 251

- subsaharan africa: malaria - south east asia: dengue - latin america: dengue - south central asia: enetric fever

Question 252

What are common causes of fever in returned traveller with following incubation periods: - acute (<10 days) - intermediate (10-21 days) - chronic (> 21 days)

Answer 252

- acute (<10 days): dengue, influenza, zika - intermediate (10-21 days): malaria, viral haemorrhagic fever, typhoid - chronic (> 21 days): malaria, hepatitis, TB

Question 253

What are live vaccines available in Australia and New Zealand?

Answer 253

MMR Yellow fever BCG Varicella/Zoster Oral polio Orochol berna (cholera) IMOJEV (JE) Oral typhoid

Question 254

What is malaria?

Answer 254

Parasitic amoeba that infects erythrocytes: -P. falciparum -P. vivax -P. malariae -P. knowlesi

Question 255

What is the lifecycle of a malaria parasite?

Answer 255

1. female mosquite injects sporozoites when bites 2. Migrate to liver and replicate 3. Rupture into blood stream and infect red cells 4. Replicate in red cells and rupture 5. Gametocytes ingested by mosquito when feeding 6. complete lifecycle in mosquito gut before migrating to salivary glands for infection

Question 256

What is the role of thick and thin films in malaria diagnosis?

Answer 256

Thick = screening Thin = assess density and species

Question 257

How is severe malaria defined? What parasites causes this and how is it treated?

Answer 257

End organ dysfunction or high parasitaemia (>10%) Caused by P. falciparum (also P. vivax and knowlesi) IV artemisinin (artesunate) (rapid parasite clearance and low resistance rates)

Question 258

Which malaria parasites have dormant stages and how should they be treated?

Answer 258

P. vivax and P. ovale Primaquine for 7-14 days (need G6PD screening)

Question 259

What is the most sensitive culture site for enteric fever?

Answer 259

Bone marrow

Question 260

What is the empiric treatment for enteric fever?

Answer 260

Azithromycin or ceftriaxone (consider meropenem if acquired in Pakistan)

Question 261

What family do the following arboviruses belong to: - dengue - zika - chikungunya

Answer 261

- dengue: flavivirus - zika: flavivirus - chikungunya: alphavirus

Question 262

What mosquitos transmit: - malaria - dengue - zika - chikungunya

Answer 262

- malaria: Anopheles - dengue: Aedes - zika: Aedes - chikungunya: Aedes

Question 263

What are the 3 phases of dengue fever?

Answer 263

1. Febrile: headache, fever, myalgia Most proceed to recovery 2. Critical: Increased capillary permeability and fragility = effusions, thrombocytopenia and coagulopathy 3. Recovery: Dengue rash Fatigue

Question 264

What is antibody dependent enhancement with regard to dengue?

Answer 264

When an immune response generated (non neutralising antibodies) to a new serotype following previous serotype infection results in increased viral replication and increased cytokines -> higher risk of severe dengue

Question 265

When can PCR and NS1 rapid antigen testing be used to detect dengue?

Answer 265

First 5 days of illness

Question 266

What travel illness presents with symmetrical small joint polyarthropathy?

Answer 266

chikungunya

Question 267

When can chikungunya be detected by PCR?

Answer 267

first week

Question 268

What travel illness causes non-purulent conjunctivitis and mild oedema of hands and feet?

Answer 268

Zika

Question 269

What does HIV require to infect a cell?

Answer 269

CD4 (T-cell, monocyte, macrophage, DC, microglial) AND CCR5 (early infection) CXCR4 (late infection)

Question 270

Where does the reservoir of HIV that presents cure persist?

Answer 270

Resting memory T-cells (latent infection)

Question 271

Where is the body does early HIV infection occur?

Answer 271

Lymph systems of GIT

Question 272

What is the HIV lifecycle in a cell?

Answer 272

HIV gp120 trimer binds CD4 resulting in conformational change where gp41 stalks docks with cell membrane which results in contact of viral and cell membrane, allowing fusion and viral contents (nucleocapsid, RNA and enzymes) to enter the cell This is mediated by CCR5 in early stage In cytoplasm nucleocapsid is digested by host cell enzymes. Viral RNA is turned into DNA by reverse transcriptase enzyme RNAseH separates HIV DNA and HIV RNA In the cell nucleus viral DNA is integrated into host cell chromosome by integrase enzyme In host choromosome when neighbouring genes are active, HIV DNA is transcribed into HIV mRNA and translated into HIV proteins end enzymes These are bundled up into virion which buds off the host cell. After this a protease enzyme cleaves viral proteins into active enzymes

Question 273

What cells do HIV replicate in?

Answer 273

Active immune cells (not active or resting cells)

Question 274

What is the main way that the body tries to control HIV infection?

Answer 274

CTL killing of infected cells via HIV antigen expression on MHC-I

Question 274

Why are T-cells depleted in HIV?

Answer 274

- early loss of T-cells during maturation due to infection - chronic inflammation suppresses production

Question 275

What genetic factors are associated with slow HIV progression?

Answer 275

- HLAB57, HLAB27 - CCR5 depletion

Question 276

Why doesn't the human immune system make effective neutralising antibodies against HIV?

Answer 276

- diversity in gp120 epitopes/antigens (between strains) - important gp120 epitopes are hidden (glycosylated) - human immune system has a preference for non-binding gp120 epitopes - HIV surface has a low concentration of gp120 and antibodies are unable to cross-link

Question 277

What are broadly neutralising antibodies in HIV infection?

Answer 277

Large variable chains that bind to multiple gp120 sites that prevent gp120 binding cell

Question 278

When do the following need to be monitored on HIV treatment? - CD4 count - HIV viral load - Genotype resistance

Answer 278

- CD4 count: baseline, until returns to normal, re-check if viral load not controlled - HIV viral load: baseline, after treatment started (8-12 weeks), regular monitoring - Genotype resistance: baseline, if persistent viraemia

Question 279

What is the mechanism of action of nucleoside inhibitors (NRTIs) and examples?

Answer 279

Bind to viral reverse transcriptase at deoxynucleotide binding site, blocking DNA synthesis. Zidovudine (T), lamivudine (C), emtricitabone (C), abacavir (G), tenofovir(A)

Question 280

Which nucleoside inhibitors have a low barrier to resistance?

Answer 280

Lamivudine, emtricitabine (so need to be used as combo drugs)

Question 281

What are common side effects of the following nucleoside inhibitors? Zidovudine Abacavir Tenofovir disoproxil fumarate Tenofovir alafenamide

Answer 281

Zidovudine - lipodystrophy - metabolic toxicity - GI upset Abacavir - hypersensitivity (needs HLA-B57*01 testing Tenofovir disoproxil fumarate - nephrotoxic (tubular wasting) - reduced bone density Tenofovir alafenamide - less nephrotoxic - weight gain - dyslipidaemia

Question 282

Which NRTIs also provide treatment for hepatitis B co-infection?

Answer 282

Tenofovir (Not Lamivudine or emtricitabine due to resistance)

Question 283

What are non-nucleoside reverse transcriptase inhibitors (NNRTIs) and some examples?

Answer 283

Bind to reverse transcriptase but not at deoxynucleosdie binding sites, altering enzyme conformation and block DNA synthesis Nevirapine, efavirenz, rilpiverine, delaverdine, etravirine, doravirine

Question 284

What are common side effects of the following non nucleoside inhibitors? Nevirapine Efavirenz Rilpiverine Delaverdine Etravirine

Answer 284

Nevirapine - hypersensitivity incl fatal hepatitis (stop if rash) Efavirenz - sedation, insomnia, vivid dreams - rash (continue) - LFT derangement - dyslipidaemia Rilpiverine - prolong Qtc Delaverdine - rash (Continue) - headache Etravirine - rash (Continue) - GI side effects

Question 285

What is the mechanism of action of protease inhibitors to treat HIV and examples?

Answer 285

Block viral protease preventing maturation of virus during and after budding of virion leading to production of defective virus. Ritonavir, lopinavir, atazanavir, darunavir

Question 286

What are common side effects of protease inhibitors used to treat HIV? side effects for: - ritnoavir - lopinavir - atazanavir - darunavir

Answer 286

- GI upset - dyslipidaemia - impaired glucose tolerance - lipodystrophy ritnoavir: - poorly tolerated, used to boost other protease inhibitors - CYP3A4 interactions lopinavir: - needs BD dosing atazanavir: - elevated bilirubin - rarely renal stones darunavir: - rash (continue)

Question 287

What is the mechanism of action of integrase inhibitors and examples?

Answer 287

Inhibit viral integrase preventing integration of viral DNA into host DNA. Particularly rapid reduction in viral load Raltegravir, elvitegravir dolutegravir, bictegravir

Question 288

What are common side effects of the following integrase inhibitors: Raltegravir Elvitegravir Dolutegravir Bictegravir

Answer 288

All have small risk of neural tube defects Raltegravir - raised CK, rhabdo Elvitegravir - CYP3A4 inhibitor cobicistat in formula Dolutegravir - headache - depression/anxiety - insomnia Bictegravir - headache - GI upset - avoid dofetilide (anti-arrhythmic)

Question 289

What is the mechanism of action for the following HIV drugs? Enfuviritide Maraviroc

Answer 289

Enfuviritide - prevents fusion of viral and cell membrane Maraviroc - prevents binding to CCR5 co-receptor

Question 290

What are the preferred starting regimens for HIV?

Answer 290

1. Integrase inhibitor + 2 NRTI - Bictegravir/tenofovir alafenamide/emtracitabine - Dolutegravir/abacavir/lamivudine - Dolutegravir+ tenofovir/emtracitabine - Raltegravir + tenofovir/emtracitabine 2. INSTI + 1 NRTI if no resistance and no HBV 3. Protease inhibitor + 2 NRTI if planning to conceive (avoid integrase inhibitor)

Question 291

What time-frame should post-exposure prophylaxis be given for HIV? What is it's duration?

Answer 291

Within 72 hours of exposure Taken for 28 days

Question 292

What PEP should be used for non-occupational exposure to known HIV positive source for: - detectable or unknown viral load - undetectable viral load

Answer 292

Detectable or unknown viral load = 3 drugs (tenofovir AND lamivudine OR emtracitabine AND dolutegravir OD OR raltegravir BD OR rilpirivine OD) Undetectable viral load: no PEP

Question 293

What PEP should be used for occupational exposure to known HIV positive source for: - detectable or unknown viral load - undetectable viral load

Answer 293

Detectable or unknown viral load = 3 drugs (tenofovir AND lamivudine OR emtracitabine AND dolutegravir OD OR raltegravir BD OR rilpirivine OD) Undetectable viral load = 2 drugs (tenofovir + lamivudine OR emtracitabine)

Question 294

What PEP should be used for non-occupational exposure to unknown HIV status source?

Answer 294

2 drugs only if high risk activity or from high prevalent community (tenofovir + lamivudine OR emtracitabine)

Question 295

What is the recommended regimen for HIV PrEP?

Answer 295

Tenofovir + emtricitabine OD

Question 296

How is pneumocystis jirovecii pneumonia diagnosed?

Answer 296

PCR of induced sputum (needs high pre test probability due to colonisation)

Question 297

How is pneumocystis jirovecii pneumonia treated?

Answer 297

co-trimoxazole (10 mg/kg/day) + steroids for hypoxia

Question 298

When is PJP prophylaxis indicated for HIV?

Answer 298

Primary: CD4 < 200 Secondary: following PJP episode until immune recovery (co-trim 480 mg OD)

Question 299

How does cryptococcal infection present in HIV?

Answer 299

Meningo-encephalitis due to C. neoformans (yeast) presents with headahce and fever +/- behaviour or confusion. Meningism = late sign

Question 300

What are LP/CSF features of cryptococcal CNS infections?

Answer 300

- raised opening pressure - Normal CSF or raised WCC and protein, low glucose - halo around organism with indian ink stain - Cryptococcal antigen positive

Question 301

How is cryptococcal CNS infection treated?

Answer 301

- LP +/- shunt to relive pressure - amphotericin + flucytosine induction - cosnolidation with 8 weeks fluconazole and then maintenance therapy until immune reconstitution

Question 302

What is the most common CNS infection in patients with advanced HIV not on treatment or prophylaxis?

Answer 302

Toxoplasmosis (can reactivate at counts < 100)

Question 303

Is brain biopsy required to start treatment for toxoplasmosis?

Answer 303

No

Question 304

When should anti-retroviral treatment be started for HIV?

Answer 304

within 14 days of diagnosis except where risk of immune reconstitution inflammatory syndrome: - 6 weeks after cryptococcal meningitis - CNS TB

Question 305

What is the most common cause of infective endocarditis?

Answer 305

S. aureus

Question 306

What is the mechanism of synergy between amoxicillin and gentamicin for E. faecalis infective endocarditis?

Answer 306

Increased uptake of aminoglycoside binding by bacterium when the cell wall is altered by beta lactam

Question 307

What is the mechanism of synergy between amoxicillin and cefotaxime for E. faecalis infective endocarditis?

Answer 307

Differential saturation of E. faecalis penicillin binding proteins

Question 308

What is recommended treatment of E. faecalis endocarditis?

Answer 308

Amoxicillin AND gentamicin OR Ceftriaxone

Question 309

How frequently should blood cultures be taken in S. aureus bacteraemia?

Answer 309

Every 24-48 h until cleared

Question 310

What is standard treatment for complicated and uncomplicated MSSA bacteraemia?

Answer 310

Flucloxacillin or cefazolin Uncomplicated: 14 days Complicated: 28 days

Question 311

What are the 5 most common bacterial causes of meningitis in adults?

Answer 311

- Strep pneumoniae (most common) - N meningitidis - H influenzae - Group B strep - Listeria mononcytogenes (esp > 65)

Question 312

What CSF features support a diagnosis of bacterial meningitis?

Answer 312

- opening pressure > 20 - Protein > 1 - CSF: blood glucose ration < 0.5 - WCC > 1000 (10% cases are < 100) - Neutrophil predominant (not in Listeria)

Question 313

How is bacterial meningitis managed?

Answer 313

- dexamethasone 10 mg IV Q6H for 4 days, stopped if pneumococcal excluded - ceftriaxone +/- benzyl penicillin if at risk of listeria - vancomycin if high risk for pneumococcal (gram positive diplococci)

Question 314

What are suitable alternatives to ceftriaxone and benzylpenicillin for baterial meningitis?

Answer 314

Ceftriaxone = moxifloxacin Benzylpenicillin = co-trimoxazole

Question 315

How long do N meningitidis+ patients need to be in droplet iso for?

Answer 315

24 hours post antibiotic administration

Question 316

What is post exposure prophylaxis for N meningitidis meningitis?

Answer 316

Given to household contacts and healthcare workers who have performed airway management without a mask Rifampicin BD 4 doses Ciprofloxacin 500 mg stat Ceftriaxone 250 mg IM stat (pregnancy)

Question 317

Why does splenectomy leave patients susceptible to encapsulated bacteria?

Answer 317

Encapsulated bacteria are unable to bind complement, only mechanism of clearance is by spleen

Question 318

How is asplenism diagnosed on blood film?

Answer 318

Howell-Jolly body (nuclear remnants) = round, dark stain peripherally in red blood cells

Question 319

What encapsulated organisms can cause overwhelming infection in hypo-/asplenism?

Answer 319

- Strep pneumoniae - Haemophilus infleunzae type b - N. meningitidis

Question 320

What prophylaxis is given post splenectomy?

Answer 320

Daily amoxicillin for 3 years Back pocket script for amoxicillin

Question 321

Are live vaccines safe in asplenism?

Answer 321

Yes

Question 322

What is the structure of a pneumococcal vaccine?

Answer 322

polysaccharide molecule conjugated to a protein carrier

Question 323

What vaccinations should asplenic patients receive?

Answer 323

1. Pneumococcal vaccine: - PCV13 x1 (before PPV) - PPV 23 x3 over 5 years 1-2 weeks pre splenectomy or 1 week post 2. Meningococcal vaccine 3. Hib vaccine as adult x1(unless fully vaccinated as child) 4. Annual influenza

Question 324

What is the most common meningococcal serotype in Aus/NZ?

Answer 324

B

Question 325

What is the mechanism of action of the following anti-fungals? - azoles - polyenes (amphotericin B) - echinocandins (caspofungin)

Answer 325

azoles inhibit lanosterol 14-a-demethlase involved in ergosterol synthesis, impairing wall synthesis polyenes (amphotericin B) bind to sterols in cell membrane increasing permeability echinocandins (caspofungin) inhibit wall synthesis via inhibition of 1,3-beta-D-glucan synthesis

Question 326

What is the mechanism of drug interaction with azoles?

Answer 326

Inhibit CYP450

Question 327

What is the key limitation of echocandins (caspofungin) in the treatment of candida infections?

Answer 327

Minimal CNS penetration

Question 328

What drugs interact with echinocandins (caspofungin)?

Answer 328

Cyclosporin Tacrolimus Rifampicin Phenytoin Carbamazepine

Question 329

What is empiric treatment of candidaemia?

Answer 329

Caspofungin, stepped down to fluconaxzole if susceptible and blood cultures cleared

Question 330

What is the clinical significance of Candida auris?

Answer 330

Often resistant to echocandins and amphotericin B Still treat with echocandins as first line

Question 331

What is the mechanism of resistance of MRSA?

Answer 331

mecA gene carried on mobile genetic element (staphylococcal cassette chromosome SCCmec) mecA encodes PBP2a which is a transpeptidase with poor affinity to beta lactams

Question 332

What antibiotics are effective for MRSA?

Answer 332

- Vancomycin (glycopeptide, cell wall) - teicoplanin (glycopeptide, cell wall) - daptomycin (affects cell membrane, poor CNS) - ceftaroline (high affinity for PBP2a) - Quinupristin-dalfopristin (50s ribosome, bacteriocidal) - Linezolid (50s ribosome, bacteriostatic, bone marrow suppression) - clindamycin (50s ribosome, bacteriostatic) - co-trim (sulfa = competes with PABA, trim blocks dihydrofolate reductase, together block 2 steps in nucleic acid and protein synthesis bacteriostatic)

Question 333

What is the mechanism of resistance VRSA?

Answer 333

Acquisition of plasmid containing vanA gene from resistant enterococci, which alters peptidoglycan terminus( D-Ala to D-Lac) to prevent binding

Question 334

What antibiotics are enterococci intrinsically resistant to?

Answer 334

- cephalosporins - macrolides - glycopeptides - tetracyclines - fluroquinolones (E. faecalis is sensitive to amoxicillin, but E. faecium is not)

Question 335

What is the difference between VanA and VanB resistance?

Answer 335

VanB is susceptible to teicoplanin

Question 336

What antibiotics can be used for VRE?

Answer 336

- linezolid - daptomycin - tigecycline - quinupristin-dalfopristin

Question 337

What is the mechanism of acquisition of ESBL genes?

Answer 337

Transferred on plasmids

Question 338

What are ESCAPPM organisms?

Answer 338

Organisms that carry an inducible cephalosporinase on Chromosomal AmpC Enterobacter Serriatia Citrobacter freundii Acinetobacter (aeromonas) Proteus (not mirabilis) Providencia Morganella morganii

Question 339

What antibiotics can be used for ESCAPPM organisms?

Answer 339

- carbapenems (ertapenem not fo acinetobacter) - piperacillin-tazabactam

Question 340

What are mechanisms of carbapenem resistance?

Answer 340

Efflux pumps Porin mutations Carbapenemase: - KPC - NDM - IMP - VIM - OXA-48 - OXA-181

Question 341

What antibiotics can be used for carbapenem-resistant organisms?

Answer 341

Combo therapy: - colistin (bacterial cell membrane) - tigecycline (30s ribosome, bacteriostatic) - amikacin (aminoglycoside 30s ribosome)

Question 342

How is TB spread?

Answer 342

Droplets

Question 343

What proportion of latent TB reactivate?

Answer 343

10%

Question 344

Is there cross-reactivity of the TB IGRA to BCG and NTM?

Answer 344

No

Question 345

How does MTB appear under microscopy with acid-fast stain?

Answer 345

Thin curved rod Ziehl-Neelsen = red Auramine = yellow/orange

Question 346

What is the gold standard for TB diagnosis and susceptibility testing?

Answer 346

Culture (liquid = 6 weeks, solid = 8 weeks)

Question 347

What is treatment for latent TB?

Answer 347

9 months isoniazid OR 4 months rifampicin

Question 348

How is active TB treated?

Answer 348

2 months: (RHEZ) - rifampicin (R) - isoniazid (H) - ethambutol (E) - pyrazinamide (Z) Then 4 months (RH) (new evidence showing 8 weeks rifapentine +H+Z+moxi then 9 weeks rifapentine + H+ moxi non inferior)

Question 349

What are common adverse drug reaction for the following anti-TB drugs? - Rifampicin - isoniazid - ethambutol - Pyrazinamide

Answer 349

Rifampicin: - drug interactions (pgp inducer, inducer CYP450) - hepatitis - hypersensitivity Isoniazid: - hepatitis - rash - peripheral neuropathy Ethambutol: - optic neuropathy Pyrazinamide: - hepatitis - skin - polyarthralgia - gout