Tropical and Travel-Related Infections — Written Clinical Reasoning

SAQ 1 — Integrated Management of Severe Falciparum Malaria (20 marks, 30 minutes)

Prompt: Outline your integrated management plan for this patient with severe falciparum malaria, including: (a) how you confirm severity and the implications for triage; (b) the specific antimalarial regimen with exact drug, dose, route, timing, and rationale; (c) supportive care in the first 48 hours; (d) the complication you must monitor for over the subsequent four weeks and why; (e) the public health and follow-up considerations; and (f) the common exam trap in the diagnostic workup. [1]

Model Answer

(a) Confirm severity and triage (3 marks): [1]

This patient has severe falciparum malaria by multiple WHO criteria. She has impaired consciousness (GCS 13), jaundice (bilirubin above 50 micromol/L), hyperparasitaemia (9 per cent), metabolic acidosis (bicarbonate below 15, lactate above 5), renal impairment (creatinine above 265 by some thresholds; this patient is at 245 with oliguria likely), and a coagulopathy (INR 1.6). Any one of these mandates parenteral therapy. She is a returning traveller from sub-Saharan Africa who took incomplete prophylaxis — the GeoSentinel data show malaria is the most common specific diagnosis (21 per cent) in febrile returned travellers, and VFR travellers are the highest-risk group [1]. She needs immediate admission to a high-dependency or intensive care setting: she has cerebral malaria, AKI, metabolic acidosis, and is at risk of ARDS, seizures, hypoglycaemia, and further deterioration within hours. A single blood film has confirmed the diagnosis — the rule-out-malaria-first principle is satisfied and treatment must not be delayed.

(b) Antimalarial regimen — IV artesunate (4 marks): [1]

The treatment is intravenous artesunate 2.4 mg/kg at 0, 12, and 24 hours, then daily, until oral therapy is tolerated, followed by a full course of oral artemisinin-based combination therapy (ACT, e.g. artemether-lumefantrine). The SEAQUAMAT trial established IV artesunate as superior to IV quinine in adults, reducing mortality from 22 per cent to 15 per cent — a 34.7 per cent relative reduction [2]. AQUAMAT confirmed a 22.5 per cent mortality reduction in African children [3]. Artesunate is preferred over quinine because it is more rapidly parasiticidal, simpler to administer (no loading-dose calculation, no cardiac monitoring), and safer (quinine causes hypoglycaemia from insulin stimulation — especially dangerous in pregnancy and severe disease — and is cardiotoxic, requiring ECG monitoring). IV artesunate must be given immediately severe malaria is recognised; do not wait for a higher parasitaemia or further deterioration. The first dose is the most important intervention in this patient's whole admission.

(c) Supportive care in the first 48 hours (5 marks): [1]

1. Airway and breathing: she is drowsy (GCS 13) and tachypnoeic — monitor for deterioration in consciousness requiring intubation for airway protection. Monitor oxygen saturation; if ARDS develops (bilateral infiltrates, PaO2/FiO2 below 300), use lung-protective ventilation (tidal volume 6 mL/kg predicted body weight, plateau pressure below 30 cm water).
2. Glucose: hypoglycaemia is a major cause of death in severe malaria, both from the illness itself (impaired gluconeogenesis) and from quinine (insulin stimulation) — artesunate is safer but glucose must still be checked every 2 to 4 hours and treated with IV dextrose if below 2.2 mmol/L.
3. Fluids and renal: avoid aggressive fluid loading, which worsens pulmonary oedema and ARDS. Give cautious maintenance fluid; treat AKI supportively, with renal replacement therapy if indicated. Monitor urine output hourly.
4. Seizure prophylaxis and treatment: cerebral malaria carries a risk of seizures; treat with benzodiazepines. Do not routinely use prophylactic anticonvulsants.
5. Anaemia and transfusion: transfuse packed red cells for severe anaemia (haemoglobin below 70 g/L, or higher if there is physiological compromise), being cautious of volume overload. She is at 78 g/L with ongoing haemolysis — transfuse if she drops below 70 or if she develops respiratory compromise.
6. Acidosis: the acidosis reflects the severity of the infection and tissue hypoperfusion; it improves with parasite clearance and supportive care rather than with bicarbonate.
7. Avoid: corticosteroids (no benefit, possible harm in cerebral malaria), heparin (no role for DIC), and exchange transfusion (evidence limited; reserve for extreme parasitaemia above 10 per cent with organ dysfunction, in consultation). [1]

(d) The four-week complication — post-artesunate delayed haemolysis (4 marks): [1]

This is the trap after apparent recovery. Post-artesunate delayed haemolysis (PADH) occurs 1 to 4 weeks after artesunate treatment, via the pitting mechanism: the spleen expels the dead parasite from the infected erythrocyte and returns the once-infected pitted cell to the circulation; these cells have a shortened lifespan and haemolyse a week or more later. Jauréguiberry and colleagues showed that among non-transfused travellers treated with artesunate for severe malaria, 22 per cent developed delayed haemolysis, and that it is predictable from the early concentration of once-infected erythrocytes [4]. The practical implication: check the haemoglobin weekly for 4 weeks after artesunate in this non-immune traveller, so that a Coombs-negative haemolytic anaemia is anticipated rather than presenting as an undiagnosed late collapse. Patient and GP must be informed of this in the discharge summary.

(e) Public health and follow-up (2 marks): [1]

• Malaria is notifiable in Australia and most jurisdictions — notify the public health unit.
• Counsel the patient on incomplete prophylaxis as a contributor, and on the need for full adherence and bite avoidance for any future travel, recognising that immunity is not acquired from a single infection.
• Arrange outpatient review at 1 week (clinical, haemoglobin) and weekly for 4 weeks (haemoglobin for PADH), with a final review at 1 month.
• Screen for other travel-acquired infections if not already done (HIV, viral hepatitis, strongyloides serology — especially given her Kenyan exposure and the risk of hyperinfection if she ever needs steroids) [6].

(f) The exam trap in the diagnostic workup (2 marks): [1]

The cardinal trap — and the one the examiners will test — is accepting a single negative blood film as exclusion of malaria. Parasitaemia is cyclical, and in early or partially immune infection a single film can be negative even in genuine falciparum malaria. The rule is to repeat thick and thin films every 12 to 24 hours for at least three sets over 48 to 72 hours before accepting that malaria is excluded. In this patient the film was positive on the first set, so treatment was not delayed — but the principle stands, and the registrar who discharges a febrile returning traveller after one negative film has made the single most dangerous error in tropical medicine. A rapid diagnostic test (RDT) is a useful adjunct where microscopy is delayed, but it does not quantify parasitaemia (which drives severity assessment and monitoring) and can remain positive for weeks after treated infection. [1]

SAQ 2 — Dengue with Warning Signs During the Critical Phase (10 marks)

Prompt: A 27-year-old man returns from Bali with a 4-day febrile illness, severe headache, retro-orbital pain, myalgia, and a maculopapular rash. Dengue NS1 antigen is positive. Platelets are 56 x 10^9/L and haematocrit is 0.45. On day 5 his fever settles to 37.3 degrees, but he develops abdominal pain, vomits three times, and his haematocrit rises to 0.55 with platelets now 34 x 10^9/L. Blood pressure is 100/66. Outline: (a) the significance of these findings; (b) the fluid strategy with exact fluid type, rate, and monitoring; (c) the drugs to avoid and why; and (d) the criteria for ICU escalation. [1]

Model Answer

(a) Significance — dengue with warning signs entering the critical phase (2 marks): [1]

The defervescence of fever in dengue is not recovery — it marks the onset of the critical plasma-leakage phase (days 3 to 7). This patient has WHO warning signs: abdominal pain, persistent vomiting, and a rising haematocrit with falling platelets (haematocrit risen from 0.45 to 0.55, a 22 per cent rise indicating significant plasma leakage) [5]. He is classified as dengue with warning signs, mandating admission for close monitoring and fluid therapy. The pathophysiology is antibody-dependent enhancement producing vascular endothelial dysfunction and increased capillary permeability — fluid shifts from the intravascular space into the third space, causing haemoconcentration, hypoproteinaemia, and (in the severe form) dengue shock syndrome.

(b) Fluid strategy (4 marks): [1]

• Fluid type: isotonic crystalloid — Hartmann's solution or normal saline (not hypotonic fluid, which worsens the hyponatraemia and does not stay intravascular).
• Rate: in a patient with warning signs, start 5 to 7 mL/kg/hour, titrated to the haematocrit, urine output, and vital signs. Reassess every 1 to 2 hours. If the haematocrit continues to rise or urine output falls, increase the rate; if it stabilises, taper.
• In dengue shock: a cautious isotonic crystalloid bolus of 10 to 20 mL/kg over 1 hour, repeated as needed; if shock persists, add colloid and move to ICU. The goal is to maintain effective intravascular volume during the period of capillary leak.
• Monitoring: haematocrit and platelet count every 4 to 6 hours, urine output (target above 0.5 mL/kg/hour), vital signs including pulse pressure (narrow pulse pressure of 20 mmHg or below indicates impending shock), and conscious state.
• The recovery-phase trap: as the capillary leak resolves (haematocrit falls, urine output improves, appetite returns), taper the intravenous fluid to avoid pulmonary oedema — continuing full-rate fluid into the recovery phase is a classic iatrogenic error. [1]

(c) Drugs to avoid (2 marks): [1]

Never give aspirin or NSAIDs (ibuprofen, naproxen, diclofenac) in dengue. The combination of thrombocytopenia (reduced platelet count) and platelet dysfunction (from endothelial activation) carries a high risk of severe bleeding, including gastrointestinal and intracranial haemorrhage. Paracetamol is the only antipyretic that should be used. Platelet transfusion is not given prophylactically for thrombocytopenia — transfusion is reserved for clinically significant bleeding, and routine transfusion of stable thrombocytopenic patients causes harm (fluid overload, transfusion reactions, and paradoxical worsening). [1]

(d) Criteria for ICU escalation (2 marks): [1]

Escalate to ICU if there is any of: dengue shock syndrome (hypotension or narrow pulse pressure with signs of hypoperfusion — cold peripheries, delayed capillary refill, oliguria), severe bleeding, severe organ impairment (AST or ALT above 1000, impaired consciousness or encephalopathy, myocarditis), or respiratory compromise from pleural effusions or ARDS. Untreated dengue shock syndrome has a mortality above 20 per cent; with good supportive care it falls below 1 per cent — early recognition and judicious fluid are the interventions that close that gap. [1]