Tropical and Travel-Related Infections — Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mrs Amara Okonkwo is a 38-year-old nurse, born in Nigeria and now living in Sydney, who returned 6 days ago from a 3-week trip visiting family in rural Imo State. She took atovaquone-proguanil prophylaxis but missed the final week. She presents with a 3-day history of fever, chills, severe headache, and myalgia, and is now in intensive care with severe falciparum malaria. [1]

Her main problems are:

1. Severe falciparum malaria — 9 per cent parasitaemia with cerebral involvement (GCS 13), metabolic acidosis (bicarbonate 14, lactate 6.2), renal failure (creatinine 245), jaundice, and a coagulopathy
2. Acute kidney injury from acute tubular necrosis, likely to need renal replacement therapy
3. Severe malaria-associated anaemia (haemoglobin 78) from haemolysis and dyserythropoiesis, with a risk of further haemolysis from post-artesunate delayed haemolysis over the next 4 weeks
4. A risk of ARDS, seizures, and aspiration pneumonia over the next 48 hours
5. An incomplete prophylaxis history and the broader context of other travel-acquired infections that need screening at follow-up [1]

Her management to date has been immediate intravenous artesunate 2.4 mg/kg at 0, 12, and 24 hours, then daily, with supportive care in ICU — cautious fluids, glucose monitoring, and a plan for renal replacement therapy and lung-protective ventilation if required. She has now been in ICU for 36 hours; her parasitaemia has fallen to 1.5 per cent, her GCS is 14, and her lactate is improving." [1]

Examiner probing questions and model answers

Q1: "Walk me through the evidence that IV artesunate is superior to IV quinine, and when (if ever) you would still use quinine." [1]

"The evidence base is two landmark randomised trials. SEAQUAMAT, published in the Lancet in 2005, randomised over 1,400 adults in Bangladesh, India, Indonesia and Myanmar with severe falciparum malaria to IV artesunate 2.4 mg/kg at 0, 12 and 24 hours then daily, versus IV quinine with a loading dose. Mortality was 15 per cent with artesunate versus 22 per cent with quinine — a 34.7 per cent relative reduction, with a number-needed-to-treat of about 14 to save one life. Artesunate was also better tolerated: quinine caused significantly more hypoglycaemia, driven by insulin stimulation [2]. AQUAMAT, published in 2010, extended this to over 5,400 African children and showed a 22.5 per cent mortality reduction, confirming that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide. Artesunate is also simpler — no loading-dose calculation, no cardiac monitoring — and safer in pregnancy. I would still use IV quinine only if artesunate was genuinely unavailable, or in a patient with a documented severe hypersensitivity reaction to artesunate — both extraordinarily rare. The first dose of artesunate is the single most important intervention in her whole admission, and giving it immediately severe malaria is recognised is the non-negotiable principle."

Q2: "She is day 2 and improving. What is post-artesunate delayed haemolysis, and what will you do about it?" [1]

"Post-artesunate delayed haemolysis, or PADH, is a specific complication of artesunate that occurs 1 to 4 weeks after treatment, after the patient has apparently recovered. The mechanism is the pitting response — the spleen recognises the dead parasite inside the infected erythrocyte, expels it, and returns the once-infected cell to the circulation. That pitted cell has a shortened lifespan, so it haemolyses a week or more later, producing a Coombs-negative haemolytic anaemia. Jauréguiberry and colleagues showed in Blood in 2014 that among non-transfused travellers treated with artesunate for severe malaria, 22 per cent developed delayed haemolysis, and that it was predictable from the early concentration of once-infected pitted erythrocytes — a threshold of 180 million per litre discriminated those who would haemolyse with 89 per cent sensitivity [3]. The practical implication for Mrs Okonkwo is that I will check her haemoglobin weekly for 4 weeks after the artesunate course, and I will write this explicitly in the discharge summary and inform her general practitioner. If she re-presents with fatigue and jaundice in that window, PADH is the leading diagnosis, and the management is supportive — transfusion if she is symptomatic or haemodynamically compromised. It is a predictable, self-limiting complication; the harm is in not anticipating it."

Q3: "Her creatinine is rising and she is oliguric. How will you manage the kidney injury, and what is the expected trajectory?" [1]

"The kidney injury in severe malaria is acute tubular necrosis from a combination of mechanisms — hypoperfusion from the systemic illness and hypovolaemia, microvascular obstruction from sequestered parasitised erythrocytes in the renal vasculature, and, in some cases, blackwater fever from massive intravascular haemolysis causing pigment nephropathy. My management is supportive: I will avoid nephrotoxins, correct hypovolaemia cautiously (bearing in mind the risk of pulmonary oedema and ARDS), monitor urine output hourly, and institute renal replacement therapy if she develops the standard indications — refractory hyperkalaemia, severe metabolic acidosis, fluid overload, or uraemic complications. I expect the AKI to recover over 1 to 3 weeks in survivors as the parasitaemia clears and renal perfusion improves, but she is at increased long-term risk of chronic kidney disease, so I will arrange nephrology follow-up and monitor her creatinine and eGFR for several months. The key tension in her fluid management is that she needs enough intravascular volume to perfuse the kidneys, but the same volume risks worsening her ARDS — so I am guided by dynamic markers of fluid responsiveness and a conservative fluid strategy after the initial resuscitation." [1]

Q4: "Why is she drowsy, and what is the prognosis for her cognition?" [1]

"Her drowsy state is cerebral malaria — the defining severe manifestation of falciparum infection. The mechanism is the sequestration of parasitised erythrocytes in the cerebral microvasculature via cytoadherence: the parasite expresses PfEMP1 on the erythrocyte surface, which binds to endothelial receptors such as ICAM-1, causing the infected cells to stick in cerebral capillaries and venules. This produces microvascular obstruction, endothelial activation, blood-brain barrier disruption, and neuroinflammation, with ring haemorrhages visible histologically. The immediate priority is to protect her airway, treat seizures promptly, and avoid hypoglycaemia, which can mimic or worsen the encephalopathy. On prognosis: mortality in cerebral malaria is 10 to 20 per cent even with artesunate. Among survivors, most adults recover fully, but a subset — particularly children in endemic areas — have lasting cognitive and behavioural sequelae, now recognised as a significant burden. I will counsel her and her family that some recovery is expected over weeks to months, that formal cognitive assessment at 1 to 3 months is warranted if she has residual deficits, and that she should not drive or make major decisions until her cognition is clearly back to baseline." [1]

Q5: "She recovered. What travel-related infections will you screen her for at follow-up, and why does strongyloides deserve particular attention?" [1]

"Mrs Okonkwo was born in Nigeria and returns regularly — she is a visiting-friends-and-relatives traveller, the highest-risk group. At her 1-month review I will screen for the infections that are often silent but carry future risk: HIV and viral hepatitis from medical and other exposures; tuberculosis with a QuantiFERON test, given the high background prevalence; schistosomiasis serology, because freshwater exposure in Africa is common and chronic disease causes periportal fibrosis and portal hypertension; and — critically — strongyloides serology. Strongyloides stercoralis is the parasite most likely to kill her in the future if she is ever immunosuppressed, because it can complete an autoinfection cycle entirely within the host and persist for decades. If she carries it and is later given corticosteroids — for an asthma exacerbation, an autoimmune condition, or anything else — the autoinfection cycle accelerates into hyperinfection, presenting as polymicrobial Gram-negative sepsis from larvae carrying enteric bacteria out of the gut, with a mortality above 50 per cent. A systematic review found that 77 per cent of patients with strongyloidiasis have eosinophilia at diagnosis, but eosinophilia may be absent during hyperinfection [5]. The screening is a single serology test and the treatment is two doses of ivermectin — simple, safe, and life-saving. I will also request a melioidosis risk assessment only if she has travelled to the Top End or Southeast Asia, which she has not on this trip [4]. The principle is that the post-travel screen is as important as the acute management."

Q6: "How will you counsel her about future travel and prophylaxis?" [1]

"I will use the ABCD framework. Awareness — she now knows first-hand how severe malaria can be, and that having grown up in an endemic area does not confer durable immunity once she has lived outside it for years. Bite avoidance — DEET-based repellent, permethrin-treated clothing, and bed nets, remembering that Aedes mosquitoes (which transmit dengue) bite by day and Anopheles (which transmit malaria) bite from dusk to dawn. Chemoprophylaxis — she must take it correctly for any future travel to an endemic area, and I will discuss the three options (atovaquone-proguanil, doxycycline, mefloquine) with their side-effect profiles so she can choose the one she will actually adhere to; for her, given the adherence issue with the daily atovaquone-proguanil, a weekly option such as mefloquine might be considered, provided there is no neuropsychiatric contraindication. Diagnosis — she must seek medical attention within hours of any febrile illness during or after future travel, and tell the clinician where she has been. I will also offer the relevant travel vaccines (hepatitis A, typhoid, yellow fever if required) and address the broader context — that visiting friends and relatives is the highest-risk travel category and deserves the most careful pre-travel consultation." [1]

Short Case Discussion

Bedside assessment of the febrile returning traveller

Examiner instruction: "You are called to the emergency department to assess a 30-year-old man who returned 10 days ago from Indonesia with fever and headache. Describe your systematic approach to the assessment and the first investigations you would order." [1]

Candidate's model answer: [1]

"My first principle is that any febrile traveller returning from a malaria-endemic area has falciparum malaria until proven otherwise, and I rule it out first — the GeoSentinel data show malaria is the most common specific diagnosis in febrile returned travellers, at 21 per cent, and that it accounted for a third of the deaths [1]. I take a focused history and examine in parallel with ordering the first investigations.

History — five questions:

1. Where did they go, and when did they return? Indonesia is endemic for malaria (especially the eastern islands), dengue (nationwide), typhoid, and scrub typhus. The 10-day incubation is in the one-to-four-week window — the highest-yield window for malaria, typhoid, dengue, and rickettsial disease.
2. What did they do? Freshwater exposure (schistosomiasis, leptospirosis), rural travel (scrub typhus), bite history, food and water exposure (typhoid, hepatitis A), sexual and medical exposures (HIV, hepatitis).
3. What prophylaxis did they take? Malaria prophylaxis type and adherence; vaccinations.
4. What is the symptom pattern? Cyclical or continuous fever, rigors, headache, retro-orbital pain (dengue), abdominal pain, diarrhoea, rash, bleeding.
5. Are there comorbidities or immunosuppression? That changes both the differential and the urgency. [1]

Examination — look for the discriminating signs:

• Temperature and pulse pattern — relative bradycardia (Faget sign) suggests typhoid; a high fever with normal or low pulse can also occur in leptospirosis and rickettsial disease.
• Skin — petechiae and a positive tourniquet test suggest dengue; a maculopapular rash involving palms and soles suggests rickettsial disease; rose spots suggest typhoid; an eschar is pathognomonic for scrub typhus; larva currens (a rapidly migrating serpiginous weal) suggests strongyloides. Examine the whole skin, including scalp, axillae, groin, popliteal fossae and interdigital webs, for an eschar.
• Abdomen — hepatosplenomegaly suggests malaria, typhoid, or visceral leishmaniasis; right-upper-quadrant tenderness with hepatomegaly suggests an amoebic liver abscess or dengue hepatitis.
• Eyes — conjunctival suffusion is the single most specific bedside sign of leptospirosis; subconjunctival haemorrhage occurs in leptospirosis and viral haemorrhagic fevers.
• Lymph nodes — generalised lymphadenopathy suggests HIV seroconversion or a viral illness; regional lymphadenopathy near an eschar supports scrub typhus.
• Hydration and perfusion — capillary refill, mottling, blood pressure, pulse pressure (narrow in dengue shock), urine output.
• Conscious state — any impairment in a febrile traveller is cerebral malaria, scrub typhus meningoencephalitis, typhoid encephalopathy, or dengue encephalopathy until proven otherwise. [1]

The minimum investigation set, ordered immediately:

1. Thick and thin blood films for malaria — the rule-out-malaria-first principle; I will repeat them every 12 to 24 hours for three sets if negative.
2. Malaria rapid diagnostic test if microscopy is delayed.
3. Full blood count and differential — thrombocytopenia (malaria, dengue), leucopenia (dengue, typhoid), eosinophilia (helminths), atypical lymphocytes (viral).
4. Urea, electrolytes, liver function tests — jaundice and renal failure indicate severe disease.
5. Blood cultures — typhoid, melioidosis, leptospirosis.
6. C-reactive protein, lactate, venous blood gas, coagulation.
7. Dengue NS1 antigen and serology if in the first 5 days; IgM and IgG after day 5.
8. Urinalysis, chest X-ray.
9. Targeted tests based on exposure: schistosomiasis and strongyloides serology, leptospirosis serology (acute and convalescent), rickettsial serology, amoebic serology and a liver ultrasound if an abscess is suspected. [1]

If the traveller has been in a viral haemorrhagic fever endemic area within 21 days, I isolate them in a negative-pressure room, notify public health, and use full PPE before any blood sampling. But for this patient, returning from Indonesia, the immediate priority is the malaria film and the minimum dataset — I will not let the workup delay the first artesunate dose if the film is positive for falciparum with any severity feature." [1]