Tropical and Travel-Related Infections — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Mrs Amara Okonkwo, 38 years old, registered nurse, born in Nigeria, resident in Sydney for 12 years. [1]

Presenting complaint: Follow-up review 6 weeks after hospital discharge for severe falciparum malaria. She is now at home and attending an outpatient review in the infectious diseases clinic. [1]

History of presenting complaint (the index admission): Six weeks ago, Mrs Okonkwo returned from a 3-week trip visiting family in rural Imo State, Nigeria. She had taken atovaquone-proguanil prophylaxis but ran out in the final week and did not replace it. Six days after return she developed fever, chills, severe headache, and myalgia, and presented to the emergency department, where she was found to be drowsy (GCS 13), jaundiced, and oliguric. Thick blood film showed Plasmodium falciparum with 9 per cent parasitaemia. She had metabolic acidosis (bicarbonate 14, lactate 6.2), AKI (creatinine 245), thrombocytopenia (platelets 48), and a coagulopathy (INR 1.6). [1]

ICU course: She was admitted directly to intensive care and given intravenous artesunate 2.4 mg/kg at 0, 12, and 24 hours, then daily. Over the first 48 hours she developed ARDS (PaO2/FiO2 180) requiring lung-protective ventilation for 4 days, and AKI requiring continuous renal replacement therapy for 5 days. Parasitaemia cleared by day 3 and her conscious state improved to GCS 15 by day 4. She was extubated on day 5 and transferred to the ward on day 8, where she completed a full course of oral artemether-lumefantrine. She was discharged home on day 14 with haemoglobin 102 g/L and creatinine 165 micromol/L (baseline 78). [1]

Past history:

• Migraine.
• No prior splenectomy; splenomegaly noted during this admission (17 cm).
• Two previous uncomplicated vaginal deliveries.
• Notionally immune to hepatitis B from childhood vaccination. [1]

Current medications:

• Ferrous sulfate 325 mg daily (for anaemia).
• Paracetamol as required for residual headache. [1]

Social history: Lives with her husband and two children (aged 8 and 10) in Sydney. Works part-time as a nurse in a general practice. Travels to Nigeria every 2 to 3 years to visit family. Non-smoker, does not drink alcohol. She holds a driver's licence and is keen to return to work. [1]

Current symptoms at the 6-week review:

• Persistent fatigue and poor concentration; she describes "brain fog" and has had to re-read documents several times.
• A single episode of dark urine 3 days ago, which she attributes to dehydration; no current jaundice.
• Residual mild headache.
• No fever, rigors, or respiratory symptoms.
• She has not yet returned to work or to driving. [1]

Examination findings (trainee elicits):

• Alert, oriented, but slow in responses. Montreal Cognitive Assessment (MoCA) 25/30 (impaired in attention and recall domains).
• Afebrile, blood pressure 118/74, heart rate 84, respiratory rate 16, oxygen saturation 98 per cent on room air.
• Mild pallor. No jaundice. No eschar, rash, or lymphadenopathy.
• Splenomegaly 3 cm below the costal margin (improving from 17 cm on admission ultrasound).
• No focal neurological deficits; no meningism.
• Cardiovascular and respiratory examination unremarkable. [1]

Investigations (current):

• FBC: haemoglobin 84 g/L (was 102 at discharge), MCV 88, white cells 6.8, platelets 210, reticulocytes 220 x 10^9/L, absolute eosinophil count 0.7 x 10^9/L.
• Film: no malaria parasites. No atypical features. Coombs test negative.
• Urea and electrolytes: creatinine 132 micromol/L (baseline 78), eGFR 48.
• Liver function tests: bilirubin 42 micromol/L (mostly unconjugated), ALT 38, AST 42, albumin 38.
• Lactate dehydrogenase 620 U/L (raised). Haptoglobin low.
• HIV, hepatitis B and C serology (taken in ICU): negative.
• QuantiFERON-TB Gold: pending.
• Strongyloides serology: pending.
• Schistosoma serology: pending. [1]

Candidate's structured presentation (model)

SASPOP opening statement: [1]

"Mrs Amara Okonkwo is a 38-year-old nurse, born in Nigeria and resident in Sydney, who is reviewed 6 weeks after surviving severe falciparum malaria — 9 per cent parasitaemia with cerebral involvement, metabolic acidosis, AKI requiring continuous renal replacement therapy, and ARDS requiring ventilation — acquired during a trip to rural Nigeria with incomplete malaria prophylaxis. She now presents with the constellation of post-malaria sequelae: cognitive impairment, a falling haemoglobin consistent with post-artesunate delayed haemolysis, and progressive chronic kidney disease — alongside the unfinished business of a post-travel screen for the other infections her exposure puts her at risk for." [1]

Structured problem list: [1]

1. Post-artesunate delayed haemolysis (PADH) — haemoglobin fallen from 102 at discharge to 84 at 6 weeks, with unconjugated hyperbilirubinaemia, reticulocytosis, raised LDH, low haptoglobin, and a negative Coombs test and film.
2. Post-malaria cognitive impairment — MoCA 25/30, impaired in attention and recall, with functional impact on work and driving.
3. Progressive chronic kidney disease — creatinine 132 (eGFR 48) at 6 weeks, down from a baseline eGFR of about 85; partial recovery from the AKI but not yet back to baseline.
4. Uncompleted post-travel screen — QuantiFERON, strongyloides, and schistosomiasis serology pending; she is a high-risk visiting-friends-and-relatives traveller.
5. Future travel and prophylaxis planning — incomplete prophylaxis was the precipitant; she travels regularly and needs a robust plan. [1]

Integrated management plan

1. Post-artesunate delayed haemolysis:

• The haematology picture is classic PADH: a Coombs-negative haemolytic anaemia developing 1 to 4 weeks after artesunate, via the pitting mechanism — the spleen returns once-infected erythrocytes to the circulation with a shortened lifespan, and they haemolyse later. Jauréguiberry and colleagues found that 22 per cent of non-transfused travellers treated with artesunate for severe malaria developed delayed haemolysis [3].
• Check haemoglobin weekly until it stabilises and then recovers; PADH is self-limiting.
• Transfuse packed red cells if she becomes symptomatic (dyspnoea, angina, presyncope) or the haemoglobin falls below 70 g/L.
• Counsel her that the dark urine episode reflects ongoing haemolysis, not recurrent malaria, and that it will settle.
• She does not need a repeat malaria film unless she develops fever — but she should be told to present immediately with any fever, as recrudescence, while uncommon after artesunate, is possible.

2. Post-malaria cognitive impairment:

• The MoCA of 25 reflects post-malarial neurological sequelae — the neuroinflammation and blood-brain barrier disruption of cerebral malaria, compounded by the metabolic disturbances and sedation of critical illness. Some recovery is expected over 3 to 6 months.
• Refer for formal neuropsychological assessment to characterise the affected domains and establish a baseline.
• Advise against driving and return to safety-critical work until cognition is clearly back to baseline; this is a licensing and medico-legal issue, not merely a clinical one.
• Reassure her that the prognosis for full recovery is good in adults, while acknowledging the small subset with persistent deficits. [1]

3. Progressive chronic kidney disease:

• Her eGFR is 48 at 6 weeks, down from a baseline of about 85. She has had partial recovery from the AKI but is at increased long-term risk of CKD progression.
• Refer to nephrology for structured follow-up; monitor creatinine and eGFR every 2 to 4 weeks initially, then every 3 months.
• Optimise blood pressure (target below 130/80), avoid nephrotoxins, and ensure she avoids non-steroidal anti-inflammatories.
• Screen for and manage the usual CKD risk factors — but she is young and otherwise well, so the trajectory should be favourable with monitoring. [1]

4. Uncompleted post-travel screen:

• Strongyloides serology is the priority. She was born in Nigeria and returns regularly — strongyloides is the parasite most likely to cause a fatal hyperinfection if she is ever immunosuppressed, and a systematic review found that 77 per cent of infected patients have eosinophilia at diagnosis (though it may be absent in hyperinfection) [4]. Her current eosinophil count is 0.7 (borderline) — if the serology is positive, treat with ivermectin 200 micrograms/kg for two doses, and document this in her record so no clinician ever starts her on corticosteroids without screening again.
• Schistosoma serology — if she had freshwater exposure in Nigeria (which I will ask about explicitly), praziquantel is curative and prevents the chronic complications of periportal fibrosis and portal hypertension.
• QuantiFERON-TB — if positive, exclude active tuberculosis and consider treatment for latent TB infection given her background risk.
• Re-screen for HIV and viral hepatitis at 3 and 6 months (she was negative in ICU, but seroconversion from exposures during travel may not yet be detectable at 6 weeks).

5. Future travel and prophylaxis planning:

• Use the ABCD framework: Awareness, Bite avoidance, Chemoprophylaxis, and prompt Diagnosis.
• Address the prophylaxis adherence issue directly — she ran out and did not replace the atovaquone-proguanil. Discuss the three options (atovaquone-proguanil daily with a 7-day post-travel course; doxycycline daily with photosensitivity and a 4-week post-travel course; mefloquine weekly with neuropsychiatric side effects) and help her choose the one she will actually adhere to. For a frequent traveller who struggled with daily dosing, the weekly mefloquine might suit — provided there is no neuropsychiatric contraindication.
• Ensure hepatitis A and typhoid vaccination are up to date.
• Advise that she will not develop durable immunity from a single infection and must not assume protection for future travel. [1]

Examiner discussion questions

Q1: "Why did her haemoglobin fall at 6 weeks, and how do you distinguish post-artesunate delayed haemolysis from recrudescence of malaria?" [1]

"The fall in haemoglobin, with unconjugated hyperbilirubinaemia, reticulocytosis, raised LDH and low haptoglobin, and a negative Coombs test and malaria film, is classic post-artesunate delayed haemolysis. The mechanism is the pitting response — the spleen removes the dead parasite from an infected erythrocyte and returns the once-infected pitted cell to the circulation, where its shortened lifespan leads to haemolysis 1 to 4 weeks later. Jauréguiberry showed this occurs in 22 per cent of non-transfused travellers treated for severe malaria [3]. I distinguish it from recrudescence by the film — recrudescence would show parasites, whereas PADH has a parasite-negative film — and by the haematology pattern, which is a Coombs-negative haemolytic anaemia rather than the haemolysis of active parasitaemia. PADH is self-limiting and managed supportively; recrudescence would require retreatment with an ACT. I would still recheck a film if she developed fever, but the current picture is PADH."

Q2: "Her MoCA is 25 at 6 weeks. What is the mechanism of the cognitive impairment, and what is the prognosis?" [1]

"Cerebral malaria is caused by the sequestration of parasitised erythrocytes in the cerebral microvasculature via cytoadherence — the parasite's PfEMP1 binds endothelial receptors such as ICAM-1, causing microvascular obstruction, blood-brain barrier disruption, and neuroinflammation, with ring haemorrhages visible histologically. Her cognitive impairment at 6 weeks reflects this neuroinflammation compounded by the metabolic disturbances of critical illness (hypoxia, acidosis, hypoglycaemia) and the residual effects of sedation. The prognosis in adults is generally favourable — most recover over weeks to months — but a subset of patients, particularly children in endemic areas, have persistent cognitive and behavioural sequelae that are now recognised as a significant disease burden. I would arrange formal neuropsychological assessment now and repeat the MoCA at 3 months, advise against driving and safety-critical work until cognition is clearly back to baseline, and offer supportive rehabilitation. I would also exclude reversible contributors — depression, sleep disturbance, anaemia, and thyroid dysfunction — before attributing it all to the malaria." [1]

Q3: "She is keen to return to work as a nurse. How will you advise her?" [1]

"This requires a functional, not just a biochemical, assessment. Her cognitive impairment (MoCA 25, with attention and recall deficits and self-reported brain fog) directly affects her ability to perform safety-critical nursing tasks — drug calculations, clinical decision-making, and recognising deterioration in patients. I would advise against an immediate return to clinical work, and instead recommend a graded return: a period of leave, then possibly administrative or non-clinical duties, then supervised clinical work, then independent practice — guided by repeat cognitive assessment. The same principle applies to driving: her slowed processing and attention deficits are a road-safety issue, and I have a medico-legal obligation to counsel her and, depending on the jurisdiction and the severity, to consider reporting. I would involve her treating team, her occupational health service, and her GP in a coordinated plan, and set clear, measurable milestones for return — a normal MoCA, no fatigue on a full day's activity, and her own sense of readiness — rather than a date alone." [1]

Q4: "Her strongyloides serology comes back positive. What do you do, and why is this particularly important for her?" [1]

"I treat her with ivermectin 200 micrograms/kg orally for two doses on consecutive days, and I document the diagnosis prominently in her medical record, her discharge summary, and a letter to her GP. The reason this is particularly important is that strongyloides is the parasite most likely to kill her in the future. Strongyloides stercoralis can complete an autoinfection cycle entirely within the host, enabling decades of silent chronic infection. If she is ever given corticosteroids — for an asthma exacerbation, an autoimmune condition, or anything else — the autoinfection cycle can accelerate into hyperinfection, presenting as polymicrobial Gram-negative sepsis (because migrating larvae carry enteric bacteria out of the gut), with a mortality above 50 per cent. A systematic review found that while 77 per cent of infected patients have eosinophilia at diagnosis, eosinophilia may be absent during hyperinfection [4], so a normal eosinophil count in the future must never be used to exclude it. Treating her now, before any future immunosuppression, is the single most effective intervention to prevent this catastrophe. I would also re-test after treatment to confirm clearance, since ivermectin has a small failure rate, and I would screen her children and husband if they have shared her exposures."

Q5: "How do you counsel her about future travel, given that she travels to Nigeria every 2 to 3 years?" [1]

"I use the ABCD framework, but I tailor it to her as a visiting-friends-and-relatives (VFR) traveller — the highest-risk group for both falciparum malaria and typhoid, because VFR travellers often assume immunity they no longer have and frequently decline or omit prophylaxis. Awareness — I explain directly that living in Sydney for 12 years means she has lost any childhood immunity to malaria, and that her recent severe illness is a realistic preview of the risk on every future trip. Bite avoidance — DEET-based repellent, permethrin-treated clothing, and bed nets, remembering that Anopheles mosquitoes bite from dusk to dawn. Chemoprophylaxis — I address the adherence issue head-on: she ran out and did not replace her atovaquone-proguanil, and that gap is almost certainly why she acquired malaria. I offer the three options and help her choose one she will adhere to for the whole trip and the required post-travel course; for her, the weekly mefloquine might suit better than daily atovaquone-proguanil, provided there is no neuropsychiatric contraindication. Diagnosis — she must seek medical attention within hours of any febrile illness during or after travel and tell the clinician where she has been. Finally, I ensure her hepatitis A and typhoid vaccinations are current, I offer a flu shot, and I arrange to see her before her next trip for a dedicated pre-travel consultation. The GeoSentinel data show that a structured pre-travel consultation substantially reduces the burden of travel-related illness [1]."