Mock Infectious Diseases Module 5

A 58-year-old man is 45 days post bilateral lung transplantation (donor CMV IgG positive, recipient CMV IgG negative).

He received basiliximab induction and is maintained on tacrolimus, mycophenolate mofetil and prednisolone. He presents with fever, dyspnoea and dry cough.

Investigations reveal:

• Haemoglobin 95 g/L (135–175)
• White cell count 2.8 × 10⁹/L (4.0–11.0)
• Neutrophils 1.6 × 10⁹/L (2.0–7.5)
• Lymphocytes 0.6 × 10⁹/L (1.0–4.0)
• Platelets 92 × 10⁹/L (150–400)
• ALT 145 U/L (<35)
• Creatinine 130 µmol/L (60–110)
• CMV PCR (whole blood): 250,000 IU/mL
• HRCT chest: bilateral ground glass opacities with small centrilobular nodules
• Bronchoalveolar lavage: CMV PCR positive, viral inclusion bodies on cytology

Which of the following best explains the mechanism by which cytomegalovirus establishes and reactivates from latency in this patient?

A 42-year-old woman is 6 months post allogeneic haematopoietic stem cell transplant (HSCT) for AML from a matched unrelated donor. She received letermovir prophylaxis for the first 100 days.

She presents with 2 weeks of watery diarrhoea (6–8 stools/day), abdominal cramps and 4 kg weight loss.

Investigations:

• Haemoglobin 88 g/L (115–165)
• Neutrophils 1.2 × 10⁹/L (2.0–7.5)
• Platelets 65 × 10⁹/L (150–400)
• ALT 42 U/L (<35), Albumin 28 g/L (35–50)
• CRP 78 mg/L (<5)
• Stool culture, C. difficile toxin, ova/cysts/parasites: negative
• CMV PCR whole blood: 850 IU/mL (low-level)
• CMV IgG positive, IgM negative
• Colonoscopy: multiple shallow ulcers throughout the colon
• Biopsy: intranuclear “owl’s eye” inclusions with positive CMV immunohistochemistry

Which of the following is the most appropriate initial therapy?

A 21-year-old university student presents with 10 days of fever, sore throat, fatigue and bilateral cervical lymphadenopathy.

Examination reveals exudative tonsillitis, tender posterior cervical lymphadenopathy and splenomegaly 3 cm below the costal margin. She was treated with amoxicillin 4 days ago by her GP and developed a widespread maculopapular rash.

Investigations:

• Haemoglobin 128 g/L (115–165)
• WCC 14.5 × 10⁹/L (4.0–11.0) with 62% atypical lymphocytes
• Platelets 110 × 10⁹/L (150–400)
• ALT 210 U/L (<35), AST 185 U/L (<35), ALP 145 U/L (30–110)
• Bilirubin 22 µmol/L (<20)
• LDH 480 U/L (120–250)
• Monospot (heterophile antibody): positive
• Throat swab: no group A Streptococcus

Which of the following serological patterns would you expect in this patient?

A 55-year-old man is 4 months post heart transplant (D+/R−). He was treated for CMV viraemia (12,000 IU/mL) with oral valganciclovir 900 mg twice daily, but after 3 weeks of therapy his CMV viral load has risen to 45,000 IU/mL.

He has developed neutropenia (neutrophils 0.8 × 10⁹/L; 2.0–7.5). Renal function is stable (creatinine 145 µmol/L; 60–110; eGFR 45 mL/min).

Investigations:

• CMV genotypic resistance testing: UL97 mutation (C592G) detected; UL54 wild-type
• No evidence of tissue-invasive disease

Which of the following is the most appropriate next therapy?

A 28-year-old woman is 8 months post small bowel transplant. Pre-transplant EBV serology showed she was EBV IgG negative; her donor was EBV IgG positive.

She received alemtuzumab induction and is maintained on tacrolimus and prednisolone. She presents with fever, night sweats, 6 kg weight loss and right cervical lymphadenopathy.

Investigations:

• Haemoglobin 98 g/L (115–165), WCC 3.8 × 10⁹/L (4.0–11.0), Platelets 140 × 10⁹/L (150–400)
• LDH 680 U/L (120–250)
• EBV PCR whole blood: 250,000 copies/mL (previously undetectable pre-transplant)
• CT chest/abdomen/pelvis: cervical, mediastinal and mesenteric lymphadenopathy; a mass involving the small bowel graft
• Lymph node biopsy: monomorphic CD20+ diffuse large B-cell lymphoma with EBER positivity by in-situ hybridisation

Which of the following is the most appropriate initial management strategy?

A 24-year-old unvaccinated man returns from a trip to the Philippines and presents with 4 days of high fever (39.5°C), coryza, non-productive cough and conjunctivitis.

On day 5 he develops a maculopapular rash beginning on the face and spreading caudally. Small bluish-white lesions are noted on the buccal mucosa opposite the second molars. He is admitted for supportive care.

Investigations:

• Haemoglobin 138 g/L (135–175)
• WCC 3.2 × 10⁹/L (4.0–11.0)
• Lymphocytes 0.7 × 10⁹/L (1.0–4.0)
• Platelets 105 × 10⁹/L (150–400)
• CRP 45 mg/L (<5)
• LFTs: mildly elevated ALT 78 U/L (<35)
• Measles IgM positive, measles RNA detected on throat swab PCR
• Chest X-ray: normal

Over the following 2 years he experiences recurrent bacterial respiratory infections despite having no prior history of infections.

Which of the following best explains the mechanism of prolonged susceptibility to infection following measles?

A 19-year-old woman presents with 3 days of fever (up to 39.2°C), sore throat, cough, red eyes and runny nose.

On day 4 of illness she develops a rash that starts on her face and behind her ears, then spreads downward to her trunk and limbs.

She recently returned from a working holiday in Europe. Her childhood vaccination history is unknown.

On examination:

• Temperature 39.0°C
• Bilateral non-purulent conjunctivitis
• Small bluish-white spots on the buccal mucosa opposite the lower molars
• Confluent erythematous maculopapular rash on the face, trunk and proximal limbs
• Generalised lymphadenopathy

Investigations:

• WCC 3.8 × 10⁹/L (4.0–11.0)
• Lymphocytes 0.9 × 10⁹/L (1.0–4.0)
• Platelets 128 × 10⁹/L (150–400)
• ALT 68 U/L (<35)
• CRP 32 mg/L (<5)
• EBV VCA IgM negative, VCA IgG positive, EBNA positive
• Monospot negative
• Parvovirus B19 IgM negative

Which of the following is the most appropriate confirmatory investigation?

A 32-year-old nurse working on a general medical ward is identified as having cared for a patient subsequently confirmed to have measles. The nurse had face-to-face contact with the index patient over a 4-hour shift 48 hours ago.

She was born in 1988 and cannot recall her vaccination history. Her employment health record shows only one documented dose of MMR vaccine received in childhood. She is 14 weeks pregnant.

Investigations (performed urgently):

• Measles IgG: negative
• Measles IgM: negative
• Rubella IgG: positive
• FBC and LFTs: normal
• Beta-hCG: consistent with pregnancy

Which of the following is the most appropriate management?

A 34-year-old previously healthy man presents with a 4-day history of fever, malaise and a widespread vesicular rash.

He is a father of two young children who had chickenpox 2 weeks ago. He was not vaccinated as a child and cannot recall having chickenpox himself.

He develops progressive dyspnoea and hypoxia on day 5 of illness.

Examination:

• Temperature 38.9°C, RR 28, SpO₂ 88% on room air
• Widespread vesicular rash in various stages of evolution (macules, papules, vesicles, crusts) on the trunk, limbs and scalp
• Bilateral inspiratory crackles
• No skin infection

Investigations:

• Haemoglobin 132 g/L (135–175)
• WCC 6.2 × 10⁹/L (4.0–11.0)
• Lymphocytes 0.8 × 10⁹/L (1.0–4.0)
• Platelets 95 × 10⁹/L (150–400)
• ALT 145 U/L (<35), AST 168 U/L (<35)
• LDH 480 U/L (120–250)
• Creatinine 105 µmol/L (60–110)
• Arterial blood gas (room air): pH 7.44, PaO₂ 55 mmHg, PaCO₂ 32 mmHg
• Chest X-ray: bilateral diffuse nodular and reticular opacities
• HRCT chest: diffuse bilateral small nodules (2–10 mm) with ground glass opacities
• VZV PCR from vesicle swab: positive
• HIV serology: negative

Which of the following is the most appropriate treatment?

A 72-year-old woman presents with a 3-day history of severe right-sided forehead pain followed by the development of a painful vesicular rash on her forehead, right upper eyelid, and the tip of her nose.

She reports blurred vision in her right eye and photophobia. She has a history of hypertension and had chickenpox as a child. She is not immunocompromised.

Examination:

• Grouped vesicles on erythematous base involving the right V1 dermatome, including the tip of the nose (positive Hutchinson’s sign)
• Right eye: conjunctival injection, corneal fluorescein staining reveals a dendritiform lesion
• Visual acuity: 6/12 right, 6/6 left
• No neurological deficit

Investigations:

• Vesicle swab VZV PCR: positive
• HIV serology: negative
• FBC, U&E, LFTs: unremarkable
• Slit lamp: pseudodendritic corneal lesion, mild anterior chamber inflammation
• IOP: right 16 mmHg, left 14 mmHg (normal 10–21)

Which of the following statements about her management and prognosis is correct?

A 62-year-old man presents with a 4-day history of fever, headache and progressive confusion, culminating in a generalised tonic-clonic seizure.

He has no significant past medical history and is not immunocompromised.

On examination he has expressive dysphasia and is disoriented.

Investigations:

• Haemoglobin 138 g/L (135–175)
• WCC 11.5 × 10⁹/L (4.0–11.0)
• CRP 28 mg/L (<5)
• Sodium 138 mmol/L (135–145), creatinine 82 µmol/L (60–110)
• CSF opening pressure 24 cm H₂O (<25)
• CSF WCC 145 × 10⁶/L (mononuclear 85%, PMN 15%), RBC 480 × 10⁶/L
• CSF protein 1.2 g/L (<0.5)
• CSF glucose 3.8 mmol/L (CSF:serum ratio 0.65) (>0.5)
• CSF HSV-1 PCR: detected
• MRI brain: asymmetric T2/FLAIR hyperintensity involving the left medial temporal lobe, insular cortex and inferior frontal lobe, with areas of restricted diffusion and small foci of haemorrhage
• EEG: left temporal lateralised periodic discharges (LPDs) at 1 Hz

Which of the following best describes the pathophysiological mechanism by which HSV-1 causes this pattern of encephalitis?

A 26-year-old woman was treated 6 weeks ago for HSV-1 encephalitis with 21 days of IV aciclovir. She had made a good recovery and was participating in rehabilitation.

Over the past 2 weeks, her family have noted new behavioural changes: agitation, insomnia, paranoid ideation and orofacial dyskinesias.

She has been increasingly withdrawn and had a witnessed generalised tonic-clonic seizure yesterday.

Examination:

• Afebrile
• GCS 13 (fluctuating), disoriented
• Orofacial dyskinesias and dystonic posturing of the upper limbs
• No focal weakness
• No meningism

Investigations:

• Haemoglobin 122 g/L (115–165), WCC 8.4 × 10⁹/L (4.0–11.0)
• CRP 6 mg/L (<5)
• Na 132 mmol/L (135–145) (mildly low)
• MRI brain: unchanged temporal lobe encephalomalacia from prior HSV encephalitis; no new lesions
• CSF opening pressure 16 cm H₂O
• CSF WCC 18 × 10⁶/L (mononuclear predominant), RBC 0
• CSF protein 0.58 g/L (<0.5)
• CSF glucose normal (CSF:serum 0.65)
• CSF HSV-1 PCR: not detected
• CSF and blood cultures: negative
• EEG: generalised slowing with an “extreme delta brush” pattern

Which of the following investigations is most likely to establish the diagnosis?

A 58-year-old man from northern Victoria presents with 5 days of fever, headache, myalgia and progressive confusion. He is a rice farmer and returned from a fishing trip along the Murray River 12 days ago.

He is otherwise well and has not travelled overseas. He received Japanese encephalitis vaccination 4 months ago as part of an occupational health programme.

On examination he is drowsy (GCS 12), febrile (38.6°C), with cogwheel rigidity in the upper limbs, hyporeflexia and flaccid weakness of the right arm.

Investigations:

• WCC 6.8 × 10⁹/L (4.0–11.0), lymphocytes 0.9 × 10⁹/L (1.0–4.0)
• Na 129 mmol/L (135–145), CRP 42 mg/L (<5)
• CSF opening pressure 22 cm H₂O
• CSF WCC 185 × 10⁶/L (30% PMN, 70% mononuclear), RBC 8 × 10⁶/L
• CSF protein 0.82 g/L (<0.5), CSF glucose 3.4 mmol/L (CSF:serum 0.6)
• CSF HSV-1/HSV-2/VZV/enterovirus PCR: not detected
• CSF and blood JEV PCR: not detected
• JEV serology (day 5 illness): IgM negative, IgG positive (titre 1:640)
• Murray Valley encephalitis virus (MVEV) IgM: negative (day 5)
• Convalescent MVEV IgM at day 24: positive (titre 1:80); MVEV total antibody positive
• MRI brain: bilateral symmetric hyperintensity of the thalami, basal ganglia and substantia nigra on T2/FLAIR, with involvement of the anterior horns of the cervical spinal cord

Which of the following mosquito species is the principal vector responsible for transmission of the causative organism in this patient?

A 74-year-old man is brought to hospital with 3 days of fever, headache and progressive confusion. He has a history of type 2 diabetes and takes metformin.

He is a retired dairy farmer and reports frequent consumption of unpasteurised milk and soft cheese.

Examination:

• Temperature 38.4°C, drowsy (GCS 13)
• Mild neck stiffness
• Cranial nerve exam: right facial nerve palsy (LMN pattern), horizontal nystagmus, dysarthria
• Ataxic gait

Investigations:

• Haemoglobin 128 g/L (135–175), WCC 14.2 × 10⁹/L (4.0–11.0)
• Neutrophils 11.5 × 10⁹/L (2.0–7.5)
• CRP 96 mg/L (<5)
• Sodium 133 mmol/L (135–145), creatinine 108 µmol/L (60–110)
• CSF opening pressure 22 cm H₂O
• CSF WCC 220 × 10⁶/L (50% PMN, 50% mononuclear), RBC 5 × 10⁶/L
• CSF protein 1.4 g/L (<0.5), CSF glucose 2.9 mmol/L (CSF:serum ratio 0.42) (>0.5)
• CSF Gram stain: no organisms seen
• MRI brain: T2/FLAIR hyperintensity involving the pons and medulla with a small ring-enhancing lesion in the pons
• Blood cultures: pending

Which of the following is the most appropriate empirical antimicrobial regimen?

A 45-year-old man with a history of relapsing-remitting multiple sclerosis, treated with natalizumab for 3 years, presents with a 6-week history of progressive right-sided weakness, subtle personality change and difficulty finding words. He has no fever, headache or seizures.

Examination:

• Afebrile, alert
• Right hemiparesis (4/5), right homonymous hemianopia, mild expressive dysphasia
• No meningism

Investigations:

• Haemoglobin 138 g/L (135–175), WCC 6.2 × 10⁹/L (4.0–11.0)
• CRP 3 mg/L (<5)
• HIV serology: negative
• Serum anti-JCV antibody index: 3.8 (high)
• CSF opening pressure 14 cm H₂O
• CSF WCC 2 × 10⁶/L (mononuclear)
• CSF protein 0.48 g/L (<0.5), CSF glucose normal
• CSF HSV/VZV/enterovirus PCR: not detected
• CSF JC virus PCR: detected (2,400 copies/mL)
• MRI brain: multifocal T2/FLAIR hyperintense lesions in the subcortical white matter of the left frontal and parietal lobes, without mass effect, minimal or no gadolinium enhancement, involving U-fibres

Which of the following is the most appropriate next step in management?

A 58-year-old woman with acute myeloid leukaemia is on day 12 of induction chemotherapy when she develops a fever of 38.6°C.

She is haemodynamically stable (BP 118/72 mmHg, HR 92 bpm). Her observations are otherwise normal and she has no localising symptoms.

Investigations:

• Neutrophils 0.1 × 10⁹/L (2.0–7.5)
• Venous lactate 1.2 mmol/L (0.5–2.2)
• Creatinine 68 µmol/L (45–90)

She is commenced on piperacillin-tazobactam.

Two days later, blood cultures taken at presentation grow an extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. She remains febrile but haemodynamically stable.

What is the most appropriate change to her antimicrobial therapy?

A 34-year-old man is on day 21 of induction chemotherapy for acute lymphoblastic leukaemia. He has had prolonged neutropenia and remains febrile despite 5 days of piperacillin-tazobactam. He develops pleuritic chest pain and a small volume of haemoptysis.

Investigations:

• Neutrophils 0.05 × 10⁹/L (2.0–7.5)
• CT chest: two peripheral nodules with surrounding ground-glass attenuation (“halo sign”)
• Serum galactomannan: positive (index 1.8)

Which organism is the most likely cause of his presentation?

A 62-year-old man with metastatic colorectal cancer is receiving total parenteral nutrition via a tunnelled central venous catheter following bowel surgery. He develops rigors and fever. He is not neutropenic. He is haemodynamically stable.

Investigations:

• Neutrophils 4.8 × 10⁹/L (2.0–7.5)
• Blood cultures (2 sets, peripheral and central): budding yeasts, subsequently identified as Candida species (speciation and susceptibilities pending)

In addition to source assessment, what is the most appropriate initial antifungal therapy?

A 56-year-old woman with diffuse large B-cell lymphoma has completed several cycles of chemotherapy and recently a 6-week course of high-dose prednisolone (30 mg daily) for autoimmune haemolytic anaemia.

She was not on any antimicrobial prophylaxis. She presents with a 5-day history of progressive dyspnoea, dry cough and fever.

Investigations:

• SpO₂ 88% on room air; PaO₂ 55 mmHg (80–100)
• CXR: diffuse bilateral interstitial infiltrates
• CT chest: extensive bilateral ground-glass opacities
• Bronchoalveolar lavage: Pneumocystis jirovecii PCR positive; Pneumocystis immunofluorescence positive

Which treatment regimen is most appropriate?

A 45-year-old man underwent splenectomy 3 years ago following a traumatic rupture. He presents with a 12-hour history of rapidly progressive fever, rigors and confusion.

Investigations:

• BP 82/48 mmHg, HR 128 bpm, T 39.4°C
• WCC 22 × 10⁹/L (4.0–11.0)
• Lactate 4.8 mmol/L (0.5–2.2)
• Blood film: gram-positive diplococci seen on buffy coat

Which mechanism best explains this patient’s heightened susceptibility to this infection?

A 39-year-old woman is 8 months post allogeneic haematopoietic stem cell transplant. She has no active graft-versus-host disease and her immunosuppression is being weaned.

Her transplant physician plans her revaccination schedule. She asks about protection against measles, as there has been a local outbreak.

Which statement regarding her vaccination is most appropriate?

A 52-year-old woman with early-stage breast cancer develops fever 10 days after adjuvant chemotherapy.

She has no COPD, is well hydrated, has mild symptoms only, and is haemodynamically stable. She has not received fluoroquinolone prophylaxis.

Investigations:

• Neutrophils 0.4 × 10⁹/L (2.0–7.5)
• Lactate 1.0 mmol/L (0.5–2.2)
• CXR: clear
• MASCC risk-index score: 23

Which management approach is most appropriate?

A 44-year-old man is 5 weeks post allogeneic HSCT. He was CMV-seropositive prior to transplant and received a graft from a CMV-seronegative donor. He is asymptomatic but routine surveillance shows a rising CMV viral load in blood.

Investigations:

• Neutrophils 1.4 × 10⁹/L (2.0–7.5)
• CMV DNA (plasma PCR): rising over two consecutive samples
• Liver function tests, chest imaging and bowel symptoms: normal / absent

What is the most appropriate management?

A 48-year-old man with rheumatoid arthritis is due to commence a TNF-α inhibitor. As part of pre-treatment screening he undergoes an interferon-gamma release assay (IGRA/QuantiFERON), which is positive.

He is asymptomatic. He was born in a country with high tuberculosis incidence.

Investigations:

• QuantiFERON-TB Gold: positive
• CXR: no active changes; no cavitation or consolidation
• Sputum: not productive; three morning specimens negative on AFB smear
• Inflammatory markers: normal

What is the most appropriate next step?

A 61-year-old woman with relapsed diffuse large B-cell lymphoma received CD19-directed CAR-T cell therapy 3 weeks ago. She has recovered from an episode of cytokine release syndrome. She now presents with recurrent sinopulmonary infections.

Investigations:

• Neutrophils 1.6 × 10⁹/L (2.0–7.5)
• IgG 2.8 g/L (7.0–16.0)
• Blood cultures: no growth
• CT sinuses: mucosal thickening consistent with sinusitis

Which underlying immune abnormality most likely accounts for her recurrent sinopulmonary infections?

A 68-year-old man presents to the emergency department with fever, dysuria and increasing confusion over 6 hours. He has a background of type 2 diabetes.

On assessment:

• Temperature 38.7°C, HR 112 bpm, RR 24/min, BP 84/48 mmHg
• Glasgow Coma Scale 14
• SpO₂ 96% on room air

Investigations:

• WCC 16.5 × 10⁹/L (4.0–11.0)
• Venous lactate 3.6 mmol/L (0.5–2.2)
• Creatinine 148 µmol/L (60–110)
• Urinalysis: leucocytes +++, nitrites positive

Blood cultures and urine cultures are taken.

Which is the most appropriate timing of empiric antimicrobial administration?

A 74-year-old woman presents to the emergency department with a 2-day history of productive cough and fever. The triage nurse is applying a screening tool to determine whether she may have sepsis requiring escalation.

On assessment:

• Temperature 38.4°C, HR 104 bpm, RR 23/min, BP 118/70 mmHg
• SpO₂ 93% on room air
• Alert and oriented

Investigations:

• WCC 14.2 × 10⁹/L (4.0–11.0)

Which statement regarding sepsis screening is most accurate?

A 59-year-old man is in the intensive care unit with septic shock secondary to community-acquired pneumonia. He has received appropriate antibiotics, source assessment and 30 mL/kg of balanced crystalloid.

Despite this, he requires ongoing noradrenaline at 0.3 µg/kg/min to maintain a mean arterial pressure of 65 mmHg, and has required this dose for the past 5 hours.

Investigations:

• Lactate 3.1 mmol/L (0.5–2.2)
• Random cortisol pending

Which is the most appropriate additional intervention?

A 63-year-old woman presents with septic shock secondary to a perforated diverticular abscess. She is being resuscitated in the emergency department.

On assessment:

• BP 82/46 mmHg, HR 118 bpm, RR 26/min
• Lactate 4.2 mmol/L (0.5–2.2)
• Creatinine 132 µmol/L (60–110)

The treating team is deciding on the initial resuscitation fluid and strategy.

Which approach is most consistent with the 2021 Surviving Sepsis Campaign guidelines?

A 70-year-old man has been in the intensive care unit for 3 weeks following septic shock due to Gram-negative bacteraemia. His initial shock resolved with resuscitation, vasopressors and antibiotics.

He now develops a new fever and clinical deterioration, and is found to have a secondary hospital-acquired infection with a different organism, together with reactivation of cytomegalovirus.

Investigations:

• Lymphocytes 0.5 × 10⁹/L (1.0–4.0)
• CMV DNA (plasma PCR): detectable

Which pathophysiological process best explains his current susceptibility to secondary infection and viral reactivation?