Severe Malaria

Quick Answer

One-liner: Severe malaria is a life-threatening complication of Plasmodium falciparum infection requiring immediate IV artesunate, intensive monitoring, and organ support.

Severe malaria occurs when P. falciparum parasitemia is complicated by organ dysfunction (cerebral malaria, ARDS, AKI, severe anemia, hypoglycemia, acidosis). Mortality is 10-20% even with treatment. Immediate action: Confirm diagnosis (thick/thin film + rapid diagnostic test), give IV artesunate 2.4 mg/kg within 1 hour, ICU admission, and notify public health (nationally notifiable disease in Australia).

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ACEM Exam Focus

Primary Exam Relevance

• Pharmacology: Artesunate mechanism (peroxide bridge activation), quinine pharmacodynamics (K-ATP channel blockade causing hyperinsulinemia)
• Pathology: Cytoadherence pathophysiology (PfEMP1 binding to EPCR/ICAM-1), sequestration causing microvascular obstruction
• Physiology: Red cell deformability, splenic pitting mechanism in post-artesunate delayed hemolysis (PADH)

Fellowship Exam Relevance

• Written: WHO severe malaria criteria, artesunate dosing regimen, exchange transfusion (no longer recommended), PADH recognition, Australian epidemiology (Torres Strait), notifiable disease requirements
• OSCE: Resuscitation of shocked patient with travel history, communication with retrieval services for Northern Australia case, informed consent for artesunate (off-label TGA), breaking bad news to family of cerebral malaria patient
• Key domains tested: Medical Expert, Health Advocate (public health notification, VFR traveler education), Communicator

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Key Points

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Epidemiology

Australian/NZ Specific

Australia (malaria-free since 1981, WHO certified):

• 400-700 imported cases annually (2015-2019): 80% P. falciparum, 15% P. vivax [PMID: 34530018]
• Torres Strait Islands: Malaria-receptive due to Anopheles farauti vector, proximity to PNG. Occasional cases (2011 Saibai/Boigu outbreak: 9 cases) [PMID: 21915470, 22262111]
• Northern Territory: Last indigenous case 1962. Remains receptive in "Top End" due to Anopheles farauti [PMID: 17615598]
• High-risk populations: VFR (Visiting Friends/Relatives) travelers to Sub-Saharan Africa, PNG, Solomon Islands (50% of imported cases)
• Nationally notifiable disease: Urgent notification to State/Territory public health units [PMID: 28061327, 31109252]

New Zealand:

• 50-100 imported cases/year (primarily Pacific islands, Africa)
• No indigenous transmission (no competent vectors)

Indigenous health disparities:

• Aboriginal and Torres Strait Islander peoples: 3-4x higher travel-related infectious disease risk due to cross-border PNG movement (Torres Strait Treaty allows traditional travel) [PMID: 22262111]
• VFR travelers from PNG/Pacific often defer chemoprophylaxis (cultural perceptions, cost, access)

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Pathophysiology

Mechanism

Severe malaria results from sequestration of parasitized red blood cells (PRBCs) in the microvasculature, causing end-organ ischemia, endothelial activation, and systemic inflammation.

1. Cytoadherence and Sequestration

• P. falciparum PRBCs express PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) on their surface
• PfEMP1 binds to endothelial receptors: EPCR (Endothelial Protein C Receptor), ICAM-1 (Intercellular Adhesion Molecule 1), CD36
• EPCR binding disrupts cytoprotective protein C pathways → pro-coagulant state [PMID: 24847880, 25501890]
• Sequestration causes microvascular obstruction in brain, lungs, kidneys, liver

2. Rosetting and Auto-Agglutination

• PRBCs bind to uninfected RBCs (rosetting) and platelets → further microvascular sludging [PMID: 22114251]

3. Endothelial Activation

• Sequestration triggers cytokine storm: TNF-α, IL-1, IL-6, IFN-γ
• Upregulation of adhesion molecules (ICAM-1) → vicious cycle
• Blood-brain barrier (BBB) breakdown: Loss of tight junctions → cerebral edema, petechial hemorrhages (Durck's granulomas) [PMID: 19468205, 23661440]

4. Organ-Specific Pathology

Cerebral Malaria:

• Sequestration in brain capillaries → hypoxia, anaerobic metabolism, lactate accumulation
• BBB disruption → cerebral edema, herniation risk
• Microhemorrhages (Durck's granulomas) [PMID: 15254661, 30349118]

Acute Kidney Injury (AKI):

• Sequestration in renal capillaries → ischemia
• Hemoglobinuria (blackwater fever): Massive intravascular hemolysis → free hemoglobin filtered by glomeruli → heme-mediated tubular toxicity (ROS, lipid peroxidation) [PMID: 25232101, 28911463, 31248503]
• Intratubular obstruction (hemoglobin casts) + NO depletion (vasoconstriction) [PMID: 24823628, 18043614]

Malaria ARDS:

• Cytokine-mediated increased capillary permeability
• Alveolar edema, impaired gas exchange
• Often delayed presentation (24-72h post-treatment initiation)

Hypoglycemia:

• Parasite consumption: P. falciparum consumes glucose 70x faster than RBCs [PMID: 2884411]
• Impaired gluconeogenesis: Cytokine (TNF-α) mediated hepatic dysfunction
• Quinine-induced: Quinine blocks K-ATP channels in pancreatic β-cells → hyperinsulinemia [PMID: 6134040]

Severe Anemia:

• RBC destruction: Hemolysis (parasitized + bystander uninfected RBCs), splenic sequestration, DIC consumption
• Bone marrow suppression (dyserythropoiesis)

Coagulopathy/DIC:

• Tissue factor release → extrinsic pathway activation
• Consumption of anticoagulants (Protein C, Antithrombin III)
• Platelet sequestration, immune-mediated destruction, consumption [PMID: 16107231, 21666793, 15328101]

Pathological Progression

P. falciparum infection 
→ Merozoite invasion of RBCs 
→ PfEMP1 expression on RBC surface 
→ Cytoadherence to endothelium (EPCR, ICAM-1) 
→ Sequestration in microvasculature 
→ Microvascular obstruction + cytokine storm 
→ Organ-specific ischemia/inflammation 
→ Cerebral malaria / ARDS / AKI / DIC 
→ Multi-organ failure / Death

Why It Matters Clinically

• Sequestration means peripheral parasitemia underestimates total body burden (mature trophozoites/schizonts sequestered in organs are not seen on blood film)
• Artesunate works by killing sequestered parasites and reducing cytoadherence → rapid clinical improvement
• Post-artesunate delayed hemolysis (PADH) occurs because artesunate allows splenic "pitting" (removal of dead parasite from intact RBC) → shortened RBC lifespan → mass hemolysis at 7-21 days [PMID: 24963041, 21251877, 25139821]

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Clinical Approach

Recognition

Think severe malaria when:

• Fever + travel to malaria-endemic area within past 3 months (up to 12 months for P. vivax/ovale)
• High-risk exposures: Sub-Saharan Africa, PNG, Solomon Islands, Indonesia
• VFR travelers (50% of cases): Often non-adherent to chemoprophylaxis
• Any organ dysfunction in a patient with confirmed/suspected malaria

Initial Assessment

Primary Survey

A - Airway:

• Assess for airway protection in altered conscious state (cerebral malaria GCS below 13)
• Seizure risk → aspiration

B - Breathing:

• RR, SpO2, work of breathing (accessory muscle use, intercostal recession)
• Malaria ARDS: Bilateral crackles, hypoxemia (PaO2/FiO2 below 300), often delayed 24-72h post-treatment
• Metabolic acidosis → Kussmaul breathing (deep, rapid)

C - Circulation:

• HR, BP, capillary refill, urine output
• Algid malaria: Circulatory collapse with cold peripheries (mimics Gram-negative sepsis)
• Fluid resuscitation targets: MAP greater than 65 mmHg, UO greater than 0.5 mL/kg/h
• AVOID fluid overload (risk of ARDS)

D - Disability:

• GCS, pupils, seizures, blood glucose
• Cerebral malaria: GCS below 11, often GCS 3-8 (unrousable coma)
• Hypoglycemia: BGL below 2.2 mmol/L (common, especially with quinine)

E - Exposure:

• Temperature (often greater than 39°C, but can be normal/hypothermic in severe cases)
• Jaundice (sclera, skin): Bilirubin greater than 50 μmol/L
• Pallor (severe anemia)
• Hemoglobinuria: Dark "Coca-Cola" urine (blackwater fever)

History

Key Questions

Red Flag Symptoms

Examination

General Inspection

• Sick or well? (Severe malaria patients look critically unwell)
• Conscious state: GCS below 11 = cerebral malaria until proven otherwise
• Respiratory distress: Kussmaul breathing (acidosis), tachypnea (ARDS/pneumonia)
• Jaundice: Scleral icterus, skin yellowing
• Pallor: Severe anemia (conjunctival, palmar)

Specific Findings

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Investigations

Immediate (Resus Bay)

Standard ED Workup

Advanced/Specialist

Point-of-Care Ultrasound

Indications:

• Cardiac: Assess volume status (IVC collapsibility), cardiac function (algid malaria can cause myocarditis)
• Lung: B-lines (ARDS, pulmonary edema)
• Abdominal: Splenomegaly (splenic rupture rare but catastrophic), free fluid (ascites in hepatic dysfunction)
• Renal: Hydronephrosis (unlikely), echogenicity (ATN)

Limitations:

• Does not diagnose malaria
• Cannot quantify parasitemia

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Management

Immediate Management (First 10 minutes)

1. ABCDE assessment (0-2 min)
   - Secure airway if GCS below 8 (RSI if cerebral malaria)
   - High-flow O2 if SpO2 below 94% (target 94-98%)
   - 2x large-bore IV access, fluid resuscitation if shocked (20 mL/kg crystalloid bolus, reassess)

2. Confirm diagnosis (2-5 min)
   - Thick/thin blood film + RDT
   - If high clinical suspicion: START TREATMENT BEFORE RESULTS (do not delay)

3. IV artesunate 2.4 mg/kg (5-10 min)
   - Reconstitute with NaHCO3, dilute in 5% dextrose or 0.9% NaCl
   - Give over 2-5 minutes IV push
   - Repeat at 12h, 24h, then daily until able to tolerate oral therapy

4. Treat hypoglycemia (if BGL below 2.2 mmol/L)
   - Adult: 50 mL 50% dextrose IV push, then 5-10% dextrose infusion
   - Child: 5 mL/kg 10% dextrose IV push, then infusion
   - Recheck BGL q1h until stable greater than 4 mmol/L

5. Anticonvulsants if seizures
   - Benzodiazepines (midazolam 5-10 mg IV)
   - Levetiracetam 1500 mg IV (avoid phenytoin - lowers artesunate levels)

6. ICU notification and transfer
   - All severe malaria → ICU
   - Notify infectious diseases, public health (notifiable disease)

Resuscitation (if applicable)

Airway

• GCS below 8 or refractory seizures: RSI with rapid-sequence induction
  • Avoid ketamine (seizure threshold), prefer propofol or thiopentone
  • "Post-intubation sedation: Propofol or midazolam infusion"
• Target: Normocapnia (PaCO2 35-45 mmHg) - avoid hyperventilation (cerebral vasoconstriction worsens ischemia)

Breathing

• Oxygen targets: SpO2 94-98% (avoid hyperoxia)
• Malaria ARDS:
  • Low tidal volume ventilation (6 mL/kg ideal body weight)
  • PEEP 5-10 cmH2O
  • Plateau pressure below 30 cmH2O
  • Consider prone positioning if PaO2/FiO2 below 150

Circulation

• Fluid resuscitation:
  • "Shocked patients: 20 mL/kg crystalloid bolus (0.9% NaCl or Hartmann's), reassess"
  • "Avoid overload: Malaria ARDS develops rapidly with excessive fluid"
  • Target MAP greater than 65 mmHg, UO greater than 0.5 mL/kg/h
• Vasopressors if fluid-refractory shock: Noradrenaline 0.05-0.5 mcg/kg/min
• Severe anemia (Hb below 50 g/L or below 70 g/L with symptoms): Transfuse PRBC 1-2 units, aim Hb greater than 70 g/L

Medications

Antimalarial Therapy

Adjunctive Therapy

Paediatric Dosing

Ongoing Management

Monitoring:

• Parasitemia: Thick/thin film q6-12h until below 1%, then daily until 3 consecutive negatives
• Blood glucose: q1-2h (especially if quinine, altered consciousness)
• Vital signs: Continuous in ICU (HR, BP, RR, SpO2, UO)
• FBC: Daily (Hb, platelets)
• Renal function: Daily (Cr, UO)
• Lactate: q6-12h if elevated
• Fluid balance: Strict I/O (risk of ARDS with overload)

Complications:

• Hypoglycemia: Recurs in 50% (especially quinine). Maintain glucose infusion, frequent BGL checks
• Seizures: 50% cerebral malaria. Benzodiazepines, levetiracetam. Avoid phenytoin
• ARDS: Develops 24-72h post-treatment. Low tidal volume ventilation, prone positioning
• AKI: 25% severe malaria. Renal replacement therapy (RRT) if oliguria, uremia, hyperkalemia
• DIC: Transfuse FFP, cryoprecipitate, platelets if active bleeding

Exchange Transfusion:

• NOT recommended by WHO/CDC (no survival benefit vs IV artesunate alone)
• Rarely considered in ultra-hyperparasitemia greater than 30% if available (case-by-case basis, no RCT evidence)

Definitive Care

ICU admission indications (all severe malaria):

• Impaired consciousness (GCS below 13)
• Respiratory distress (RR greater than 30, SpO2 below 90%)
• Circulatory collapse (SBP below 90, lactate greater than 5 mmol/L)
• AKI (Cr greater than 265 μmol/L, oliguria)
• Severe anemia (Hb below 70 g/L)
• Hyperparasitemia greater than 10%
• Hypoglycemia recurrent
• Seizures

Infectious Diseases consult: All cases (antimalarial choice, monitoring, oral step-down)

Public Health notification: Urgent notification (phone) to State/Territory health unit (nationally notifiable disease) [PMID: 28061327, 31109252]

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Disposition

Admission Criteria

All severe malaria → ICU admission:

• WHO severe malaria criteria met (see Key Points)
• Parasitemia + ≥1: Impaired consciousness, respiratory distress, circulatory collapse, jaundice, hemoglobinuria, severe anemia, hypoglycemia, acidosis, AKI, hyperparasitemia

General ward admission (uncomplicated malaria with risk factors):

• Parasitemia below 2%, no organ dysfunction, BUT:
  • Co-morbidities (pregnancy, age greater than 60, immunosuppression)
  • Social factors (homelessness, poor access to follow-up)
  • High parasite load (1-2%) requiring close monitoring

ICU/HDU Criteria

ICU:

• GCS below 13 (cerebral malaria)
• Mechanical ventilation required (ARDS, airway protection)
• Vasopressor support (algid malaria)
• Renal replacement therapy (AKI)
• Hyperparasitemia greater than 10%
• Recurrent hypoglycemia despite treatment
• Lactate greater than 5 mmol/L

HDU:

• GCS 13-14 (close monitoring for deterioration)
• Parasitemia 5-10% (risk of progression)
• AKI managed conservatively (Cr 265-500 μmol/L)

Discharge Criteria

From ICU to ward:

• Parasitemia below 1%
• No organ dysfunction
• GCS 15
• Tolerating oral antimalarials
• Hemodynamically stable (off vasopressors, no respiratory support)

From hospital:

• Parasitemia 3 consecutive negatives (thick film)
• Completed antimalarial course (or reliable for outpatient completion)
• No complications (PADH monitoring arranged)
• Follow-up arranged

Follow-up

Post-discharge:

• Week 1: ID clinic (thick film, FBC, renal function)
• Weeks 2-4: Weekly Hb (monitor for PADH - 20-30% hyperparasitemia cases develop delayed hemolysis 7-21 days post-treatment) [PMID: 24963041, 25139821]
• Week 4: Thick film (ensure parasite clearance)
• 3 months: If P. vivax/ovale, consider primaquine for radical cure (after G6PD testing)

GP letter:

• Diagnosis: Severe P. falciparum malaria
• Treatment: IV artesunate (dates), oral completion (medication, duration)
• Complications: (list any: cerebral malaria, AKI, ARDS, PADH)
• Follow-up plan: ID clinic dates, PADH monitoring (weekly Hb x 4 weeks)
• Public health notification completed
• Counseling: Chemoprophylaxis adherence for future travel, mosquito bite prevention

Specialist referral:

• Infectious Diseases: All cases (ongoing management, oral step-down, PADH monitoring)
• Nephrology: If AKI requiring RRT or persistent renal dysfunction
• Neurology: If focal neurology post-cerebral malaria (25% have sequelae: seizures, cognitive impairment, motor deficits)

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Special Populations

Paediatric Considerations

Age-specific differences:

• Higher risk severe anemia (splenic sequestration, hemolysis)
• Seizures more common (50% cerebral malaria)
• Hypoglycemia more frequent (lower glycogen stores, higher metabolic rate)
• Faster parasite clearance (age below 5 years)

Dosing: Weight-based (see Paediatric Dosing table)

Monitoring: BGL q1h (hypoglycemia risk), seizure precautions

Prognosis: Better than adults if treated early (AQUAMAT trial: 8.5% mortality with artesunate in African children) [PMID: 21062957]

Pregnancy

High-risk population:

• 3-4x higher risk severe malaria (placental sequestration, immune suppression)
• Increased risk hypoglycemia (β-cell hypertrophy + quinine)
• Maternal mortality 10-50%
• Fetal mortality 30-60% (miscarriage, stillbirth, preterm labor)

Management:

• IV artesunate (all trimesters - benefit outweighs theoretical teratogenicity risk)
• Avoid quinine if possible (severe hypoglycemia risk)
• Fetal monitoring: CTG if viable gestation (greater than 24 weeks)
• Obstetric consult: Preterm labor risk, fetal distress

Delivery: Not indicated unless fetal distress (artesunate rapidly clears parasitemia, stabilize mother first)

Elderly

Increased risk:

• Higher mortality (co-morbidities: CKD, IHD, diabetes)
• Delayed diagnosis (atypical presentation)
• Polypharmacy interactions (quinine + cardiac drugs)

Management:

• Lower threshold for ICU admission
• Careful fluid balance (cardiac/renal dysfunction)
• Renal dose adjustments (if CKD)

Indigenous Health

Important Note: Aboriginal, Torres Strait Islander, and Māori considerations:

Epidemiology:

• Torres Strait Islanders: Highest risk in Australia due to proximity to PNG, traditional cross-border travel (Torres Strait Treaty). 2011 Saibai/Boigu outbreak: 9 cases [PMID: 21915470, 22262111]
• Aboriginal Australians: Northern Australia (Northern Territory, Far North Queensland) - travel to PNG, Indonesia for work, family, ceremony
• Māori: Travel to Pacific islands (PNG, Solomon Islands, Vanuatu) for cultural/family reasons

VFR (Visiting Friends/Relatives) travelers:

• 50% of imported malaria cases in Australia are VFR travelers (travel to endemic countries to visit family)
• Non-adherence to chemoprophylaxis: Cultural perceptions ("immunity" if born in endemic area), cost (not PBS-subsidized for travel), access (remote pharmacies)
• Delayed presentation: Normalizing symptoms ("just a fever"), mistrust of healthcare systems, geographic remoteness

Cultural safety considerations:

• Family involvement: Decision-making often communal (involve whānau/family in discussions)
• Interpreter services: Provide Torres Strait Creole, Māori, or language-concordant interpreters
• Aboriginal Health Worker/Liaison: Essential for trust, cultural protocols
• Traditional medicine: Acknowledge use, ensure no contraindications with antimalarials
• Notification: Discuss public health reporting transparently (notifiable disease)

Barriers to care:

• Geographic: Remote communities (Torres Strait, Tiwi Islands, Far North QLD) - delayed diagnosis, limited ICU access
• Financial: Travel costs for specialist follow-up, accommodation for family
• Cultural: Mistrust of Western medicine, historical trauma, racism in healthcare

Health disparities:

• 3-4x higher infectious disease mortality in Aboriginal and Torres Strait Islander peoples
• Poorer outcomes due to delayed presentation, co-morbidities (diabetes, CKD), social determinants

Actions:

• Pre-travel counseling: Community health centers, Aboriginal Medical Services - emphasize chemoprophylaxis, mosquito bite prevention
• Rapid access: Northern Australia EDs maintain high index of suspicion (fever + travel history)
• Retrieval: RFDS coordination (see Remote/Rural section)
• Follow-up: Coordinate with Aboriginal Health Workers, telehealth if remote

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Pitfalls & Pearls

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Viva Practice

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OSCE Scenarios

Station 1: Resuscitation of Severe Malaria Patient

Format: Resuscitation Time: 11 minutes Setting: ED resuscitation bay

Candidate Instructions:

You are the ED registrar at Darwin Hospital. A 40-year-old mining engineer has just arrived by ambulance with a 3-day history of fever and confusion. He returned from Papua New Guinea 2 weeks ago. His colleague states he did not take malaria prophylaxis. The triage nurse has placed him in Resus Bay 1. Please assess and manage this patient in the first 10 minutes.

You have a nurse and medical student available to assist you. The thick/thin blood film will take 30 minutes to process. A rapid diagnostic test (RDT) is available.

Examiner Instructions: Patient is critically unwell on arrival:

• GCS 9 (E3 V2 M4) - responding to voice with incomprehensible sounds
• T 39.5°C, HR 125, BP 90/55, RR 30, SpO2 91% on room air
• Jaundiced, no rash, no neck stiffness
• BGL 2.0 mmol/L (if checked)
• RDT positive for P. falciparum (if requested)

Expected progression:

• If airway secured, BGL corrected, artesunate given → patient stabilizes (GCS improves to 13, BP 105/65, RR 24, SpO2 96% on O2)
• If BGL not corrected within 5 minutes → seizure (tonic-clonic, 60 seconds)
• If no artesunate by 10 minutes → examiner asks "What is your definitive treatment?"

Actor/Patient Brief: Not applicable (manikin scenario or standardized patient feigning altered consciousness - only responds to voice with groans, no coherent speech)

Marking Criteria:

Expected Standard:

• Pass: ≥6/11. Must complete primary survey, check BGL and correct hypoglycemia, request malaria diagnostics (RDT acceptable), and state IV artesunate as definitive treatment (even if not administered within 11 minutes).
• Fail: below 6/11. Common failures: Not checking BGL (patient seizes), delaying treatment until blood film results (artesunate should start on clinical suspicion if high-risk travel history + altered consciousness), not recognizing severe malaria (attributing to sepsis without considering malaria).
• Key discriminators: Immediate BGL check (critical action in altered consciousness + fever + travel), starting artesunate on clinical suspicion (not waiting for film), dose calculation (2.4 mg/kg), public health notification.

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Station 2: Communication - Informed Consent for Artesunate

Format: Communication Time: 11 minutes Setting: ED cubicle

Candidate Instructions:

You are the ED registrar at Cairns Base Hospital. A 32-year-old woman has been diagnosed with severe Plasmodium falciparum malaria (parasitemia 8%, Hb 75 g/L, GCS 15). She is currently stable but requires IV artesunate. However, artesunate is not TGA-approved for malaria in Australia (it is available via Special Access Scheme). You need to obtain informed consent from the patient for IV artesunate, explaining the risks and benefits.

The patient is a first-time traveler to PNG (visiting a friend). She is anxious and has many questions.

Examiner Instructions: Patient is alert, oriented, anxious. She has read online that "artesunate causes severe anemia weeks later" and is worried. She asks:

1. "Why do I need this drug if it's not approved?"
2. "Will I get severe anemia and need a transfusion later?"
3. "What if I just take tablets instead?"

Assess candidate's ability to:

• Explain severe malaria and urgency
• Discuss artesunate efficacy (evidence-based)
• Address PADH risk (post-artesunate delayed hemolysis)
• Explain alternatives (quinine) and why artesunate is superior
• Obtain informed consent without coercion

Actor/Patient Brief: You are Emma, a 32-year-old accountant. You traveled to PNG 3 weeks ago to visit a friend (first international trip). You felt sick for 4 days (fever, headache) before coming to hospital. You are scared because the doctor said you have "severe malaria" and need a drug that's "not approved in Australia". You read online that artesunate causes "delayed hemolysis" which sounds terrifying. You are anxious but want to understand your options.

Key concerns to raise:

• "Why do I need a drug that's not approved? Is it experimental?"
• "I read artesunate causes severe anemia weeks later - will I need a blood transfusion?"
• "Can't I just take tablets like my friend did when she had malaria?"

You will consent if the doctor:

• Explains severe malaria risk clearly (organ failure, death)
• Addresses PADH risk honestly (20-30% chance, manageable, monitoring arranged)
• Explains artesunate is gold standard internationally (WHO, evidence-based)

Marking Criteria:

Expected Standard:

• Pass: ≥6/11. Must explain severe malaria risk, artesunate rationale (gold standard, evidence-based), address PADH honestly (risk, monitoring, self-limiting), and obtain consent.
• Fail: below 6/11. Common failures: Dismissing PADH concern ("don't worry about it"), coercive consent ("you have no choice"), not explaining why artesunate over quinine, not checking understanding.
• Key discriminators: Honest discussion of PADH (risk + management + monitoring), evidence-based explanation (SEAQUAMAT/AQUAMAT trials), empathy (validates anxiety without minimizing).

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Station 3: Remote Retrieval Coordination - Torres Strait Case

Format: Communication (Phone call to RFDS) Time: 11 minutes Setting: ED office (phone scenario)

Candidate Instructions:

You are the ED registrar at Thursday Island Hospital (Torres Strait, Queensland). A 28-year-old Torres Strait Islander woman has presented with severe malaria (parasitemia 14%, GCS 12, BGL 2.5 mmol/L, Hb 68 g/L). She returned from PNG 1 week ago.

You have given IV artesunate (first dose), corrected hypoglycemia, and started fluids. She requires ICU-level care, which is not available on Thursday Island. The nearest ICU is Cairns Base Hospital (800 km, 2-hour flight).

You need to phone the Royal Flying Doctor Service (RFDS) to arrange urgent retrieval. The RFDS Flight Nurse will ask you questions to determine flight priority and resource requirements.

Examiner Instructions: You are the RFDS Flight Nurse (via phone). You will ask:

1. "What is the patient's current clinical status?" (GCS, vitals, oxygen requirement)
2. "What is the diagnosis and what treatment has been given so far?"
3. "What are the retrieval priorities and risks?" (airway, deterioration risk)
4. "Does the patient require a medical escort, or is a flight nurse sufficient?"
5. "Any family or cultural considerations for the retrieval?"

Assess candidate's ability to:

• Provide clear, structured ISBAR handover
• Communicate clinical urgency (cerebral malaria risk, GCS 12)
• Identify retrieval risks (airway, seizure, hypoglycemia recurrence)
• Advocate for medical escort (ED registrar or ICU-trained flight nurse)
• Address cultural considerations (family involvement, Torres Strait Islander patient)

Actor (RFDS Nurse) Brief: You are the RFDS Retrieval Coordinator. You need to determine:

• Flight priority (Code 1 urgent vs Code 2 semi-urgent)
• Retrieval team configuration (flight nurse only vs flight nurse + doctor)
• Aircraft type (PC-12 pressurized vs King Air)
• Estimated departure time

You will ask specific questions (as above). You are professional, direct, and focused on patient safety.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11. Must provide ISBAR handover, communicate clinical urgency (GCS 12, cerebral malaria), identify airway as major retrieval risk, and request medical escort.
• Fail: below 6/11. Common failures: Disorganized handover (no structure), underestimating urgency (GCS 12 is high-risk), not requesting medical escort (airway risk), not mentioning cultural considerations.
• Key discriminators: Identifying airway risk (GCS 12 may deteriorate to below 8 in flight, needs RSI capability), justifying medical escort (not just "I think she needs a doctor", but "high-risk airway, cerebral malaria, may require intubation mid-flight"), cultural advocacy (Torres Strait Islander family involvement).

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SAQ Practice

Question 1 (8 marks)

Stem: A 45-year-old man presents to ED with fever and confusion. He returned from Ghana 2 weeks ago. Blood film shows Plasmodium falciparum parasitemia 12%. Initial observations: GCS 11, T 39.8°C, HR 115, BP 100/60, RR 26, SpO2 95% on room air. BGL 1.9 mmol/L.

Question: List the immediate management priorities in the first 10 minutes. (8 marks)

Model Answer:

1. Correct hypoglycemia: Give 50 mL 50% dextrose IV push, then start 5-10% dextrose infusion. Recheck BGL in 30 min, then q1-2h (1 mark)
2. Secure airway: GCS 11 - at risk. Positioning (recovery position if vomiting risk), suction available. Consider definitive airway if GCS deteriorates to below 8 (1 mark)
3. Oxygen: High-flow O2 via Hudson mask 15L to target SpO2 ≥94% (RR 26 suggests respiratory distress or metabolic acidosis) (1 mark)
4. IV access and fluids: 2x large-bore IV cannulas. Crystalloid bolus 500 mL (cautious - avoid overload, risk of ARDS). Reassess BP, UO (1 mark)
5. IV artesunate 2.4 mg/kg: Immediate administration (do not wait for further results). Reconstitute with NaHCO3, dilute in 5% dextrose or 0.9% NaCl, give over 2-5 min IV. Repeat at 12h, 24h, then daily (1 mark)
6. Investigations: Thick/thin blood film already done. Also send: FBC, EUC, LFTs, coags, VBG (lactate, pH, base deficit), blood cultures (1 mark)
7. Seizure precautions: Midazolam 5-10 mg IV drawn up at bedside. Cerebral malaria (GCS below 11) has 50% seizure risk (1 mark)
8. ICU referral and notification: Call ICU for bed (severe malaria requires ICU). Notify infectious diseases and public health unit (nationally notifiable disease, urgent phone notification required) (1 mark)

Examiner Notes:

• Accept: "Glucose" instead of "50% dextrose" (as long as dose/route specified). "Artesunate" without dose acceptable if stated "as per protocol".
• Do not accept: "Admit to ICU" without actually calling ICU in first 10 minutes. "Monitor BGL" without correcting hypoglycemia (BGL 1.9 mmol/L is critical - needs immediate correction). "Wait for blood film results before giving artesunate" (high clinical suspicion + severe criteria = start artesunate immediately).

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Question 2 (6 marks)

Stem: A 32-year-old woman was treated for severe malaria (parasitemia 10%) with IV artesunate 2 weeks ago. She was discharged 10 days ago with parasites cleared. She re-presents with fatigue and dark urine for 2 days. Hb 60 g/L (was 90 g/L at discharge), bilirubin 70 μmol/L, LDH 900 U/L, haptoglobin undetectable. Blood film shows no parasites, spherocytes present. Direct Coombs test negative.

Question: What is the most likely diagnosis? Outline the pathophysiology and immediate management. (6 marks)

Model Answer:

1. Diagnosis: Post-Artesunate Delayed Hemolysis (PADH) (1 mark)
2. Pathophysiology: Artesunate rapidly kills P. falciparum parasites within RBCs. The spleen "pits" (removes) the dead parasite, leaving once-infected erythrocytes (OIEs) - RBCs with shortened lifespan (7-15 days vs 120 days normal). With 10% initial parasitemia, a large cohort of OIEs was created. At 14 days post-treatment, this cohort reaches end of lifespan → mass hemolysis by splenic clearance (1 mark)
3. Timing: Occurs 7-21 days post-artesunate, median 14 days (patient is 14 days post-treatment) (1 mark)
4. Hemolysis markers: Low Hb (90→60 g/L), elevated bilirubin, elevated LDH, undetectable haptoglobin, spherocytes (damaged RBCs), hemoglobinuria (dark urine). Negative Coombs excludes autoimmune hemolytic anemia (1 mark)
5. Immediate management: Transfuse 2 units PRBC (Hb below 70 g/L with symptoms - fatigue). Aim Hb greater than 70 g/L. Start folic acid 5 mg PO daily (supports erythropoiesis). Ensure hydration (UO greater than 0.5 mL/kg/h to prevent hemoglobin-mediated AKI). Monitor daily Hb until rising (1 mark)
6. Re-treatment NOT required: This is not relapsed malaria (blood film negative). Self-limiting (hemolysis resolves in 7-10 days). No further antimalarials. Follow-up hematology outpatient in 2 weeks (1 mark)

Examiner Notes:

• Accept: "Delayed hemolysis after artesunate" or "PADH" (any phrasing acceptable). "Splenic pitting mechanism" or "OIE clearance" for pathophysiology.
• Do not accept: "Relapsed malaria" (film is negative). "Autoimmune hemolytic anemia" (Coombs negative). "G6PD deficiency" (no trigger, wrong timing). "Give more antimalarials" (incorrect - this is not relapse).

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Question 3 (8 marks)

Stem: A 50-year-old woman presents with severe Plasmodium falciparum malaria. She is pregnant (28 weeks gestation). Parasitemia 9%, GCS 15, BGL 3.5 mmol/L, Hb 75 g/L, BP 110/70, HR 100, RR 20, SpO2 97% on room air.

Question: Outline the specific management considerations for this patient due to her pregnancy. (8 marks)

Model Answer:

1. IV artesunate is first-line: Use IV artesunate 2.4 mg/kg at 0, 12, 24h then daily (same dose as non-pregnant). Benefit outweighs theoretical teratogenicity risk. All trimesters (including first trimester if severe malaria) (1 mark)
2. Avoid quinine if possible: Quinine has 3x higher hypoglycemia risk in pregnancy due to pregnancy-induced β-cell hypertrophy. If quinine required (artesunate unavailable), continuous BGL monitoring q1h, glucose infusion mandatory (1 mark)
3. Higher risk severe disease: Pregnancy increases risk 3-4x due to placental sequestration (parasites bind to chondroitin sulfate A in placenta) and immune suppression. Lower threshold for ICU admission (1 mark)
4. Hypoglycemia monitoring: Pregnancy itself predisposes to hypoglycemia (higher insulin sensitivity, fetal glucose consumption). Check BGL q2-4h even if normal initially (1 mark)
5. Fetal monitoring: CTG (cardiotocography) if viable gestation (≥24 weeks). Monitor for fetal distress (decelerations, reduced variability). Parasitemia correlates with fetal compromise (1 mark)
6. Obstetric consultation: Early involvement. Risk of preterm labor (30-60% with severe malaria), miscarriage, stillbirth. Do NOT deliver unless fetal distress (artesunate rapidly clears parasitemia, stabilize mother first) (1 mark)
7. Anemia management: Pregnancy baseline Hb 95-120 g/L (physiological anemia of pregnancy). Transfusion threshold Hb below 70 g/L (this patient 75 g/L - monitor, transfuse if symptomatic or falling). Folic acid 5 mg daily post-acute phase (1 mark)
8. Maternal-fetal outcomes: Maternal mortality 10-50% (higher than non-pregnant), fetal mortality 30-60%. Discuss prognosis with patient and partner. Intensive monitoring in ICU (1 mark)

Examiner Notes:

• Accept: "Artesunate all trimesters" or "artesunate safe in pregnancy" (benefit outweighs risk). "Quinine causes hypoglycemia in pregnancy" (mechanism not required for full mark).
• Do not accept: "Avoid artesunate in pregnancy" (incorrect - it is first-line). "Deliver baby immediately" (incorrect unless fetal distress - stabilize mother first).

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Question 4 (6 marks)

Stem: You are the ED consultant at Cairns Base Hospital. A Torres Strait Islander patient has been diagnosed with severe malaria. You are completing the public health notification form.

Question: List the key information required for malaria notification in Australia and explain why prompt notification is critical in the Torres Strait region. (6 marks)

Model Answer:

1. Key notification information: Patient demographics (name, age, address), travel history (country, dates of travel, return date), Plasmodium species (P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi), parasitemia level, severity (uncomplicated vs severe), treatment given (artesunate, date started), outcome (admitted/discharged/ICU) (2 marks)
2. Notification timeframe: Urgent notification (phone call to State/Territory public health unit within 24h of diagnosis, ideally immediately for severe cases). Malaria is a nationally notifiable disease under NNDSS (National Notifiable Diseases Surveillance System) [PMID: 28061327, 31109252] (1 mark)
3. Torres Strait-specific urgency - competent vectors: Torres Strait has Anopheles farauti mosquitoes (competent malaria vectors). If a mosquito bites an infected patient, then bites another person, local transmission can occur (as seen in 2011 Saibai/Boigu outbreak - 9 cases) [PMID: 21915470, 22262111] (1 mark)
4. Vector control response: Public health unit coordinates rapid vector control (residual insecticide spraying, mosquito surveillance) around patient's residence to prevent local transmission (1 mark)
5. Contact tracing: Identify co-travelers (may have been exposed to same mosquitoes in PNG), household contacts (assess for symptoms, provide education on malaria recognition) (0.5 marks)
6. Surveillance: National surveillance tracks imported cases to detect clusters, monitor trends (species distribution, drug resistance), and assess risk of re-establishment of malaria in receptive areas (Torres Strait, Northern Territory) (0.5 marks)

Examiner Notes:

• Accept: "Torres Strait has malaria mosquitoes" or "competent vectors present" (doesn't need to name Anopheles farauti for full mark). "Prevent local transmission" or "vector control" (purpose of notification).
• Do not accept: "Notification is just a legal requirement" without explaining public health purpose (disease surveillance, vector control). "Torres Strait has malaria" (incorrect - Australia is malaria-free since 1981, but vectors are present = malaria-receptive).

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Australian Guidelines

Therapeutic Guidelines Australia

Malaria Management:

• Severe malaria first-line: IV artesunate 2.4 mg/kg at 0, 12, 24h then daily until able to tolerate oral therapy (TG eTG complete - Infectious Diseases)
• Oral step-down: Artemether-lumefantrine (Riamet) OR atovaquone-proguanil (Malarone) to complete 3-day course. If artesunate given below 24h, add doxycycline 100 mg BD for 7 days or clindamycin 450 mg TDS for 7 days
• Pregnancy: IV artesunate all trimesters (benefit outweighs risk). Avoid doxycycline in pregnancy (use clindamycin for completion)

Chemoprophylaxis (pre-travel):

• High-risk areas (Sub-Saharan Africa, PNG, Solomon Islands): Atovaquone-proguanil (Malarone) OR doxycycline OR mefloquine
• Low-risk areas: Chloroquine (only if chloroquine-sensitive regions)
• Torres Strait residents: Public health-subsidized prophylaxis programs for cross-border travel to PNG

National Notifiable Diseases Surveillance System (NNDSS)

Reporting requirements [PMID: 28061327, 31109252]:

• Malaria is nationally notifiable (all Plasmodium species)
• Severe malaria: Urgent phone notification to State/Territory public health unit within 24h (ideally immediately)
• Laboratories: Must notify positive malaria tests (thick/thin film, RDT, PCR)
• Clinicians: Must notify confirmed or suspected cases
• Surveillance purpose: Track imported cases, monitor species distribution, assess re-establishment risk in receptive areas (Torres Strait, NT), guide vector control

State-Specific Protocols

Queensland (Torres Strait, Far North Queensland):

• Torres Strait Malaria Surveillance Program: Active surveillance in Torres Strait Islands, vector control (residual spraying), cross-border collaboration with PNG
• Notifiable Disease Portal: Online notification system (phone notification for severe cases)
• Cairns Base Hospital: Regional reference center for Northern Australia malaria cases. ICU expertise in severe malaria management

Northern Territory:

• NT Malaria Elimination Program: Surveillance in "Top End", vector monitoring (Anopheles farauti), rapid case investigation
• Royal Darwin Hospital: Tertiary center for severe malaria in NT

New South Wales:

• NSW Health Public Health Unit: Phone notification 1300 066 055. Online portal for laboratory notifications

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Remote/Rural Considerations

Pre-Hospital

Ambulance/Primary Care (Remote Clinic):

• Recognition: Fever + travel to malaria-endemic area within 3 months (up to 12 months P. vivax/ovale) = malaria until proven otherwise
• Initial management:
  • ABCDE assessment
  • BGL check (hypoglycemia common)
  • Thick/thin blood film if lab available (remote clinics may not have microscopy)
  • RDT (rapid diagnostic test) if available (HRP-2 for P. falciparum, sensitivity 95%)
  • Oxygen if SpO2 below 94%
  • IV access, fluids if shocked
• DO NOT give oral antimalarials if severe criteria present (altered consciousness, respiratory distress, shock, hypoglycemia) - requires IV artesunate
• Retrieval: Activate RFDS immediately if severe criteria

Resource-Limited Setting

Modified approach when ICU unavailable:

• Airway: If GCS below 8, consider intubation at referring site before retrieval (RSI by experienced clinician). If no RSI capability, position patient in recovery position, suction available, prepare for airway obstruction
• IV artesunate: Give first dose at referring site (do not delay for retrieval). Many remote hospitals in Northern Australia stock artesunate (Special Access Scheme pre-authorization for malaria-endemic regions)
• BGL monitoring: q1-2h. Portable glucometer. Continuous glucose infusion if hypoglycemic (5-10% dextrose)
• Seizure management: Benzodiazepines available. Avoid phenytoin (lowers artesunate levels)
• Fluid balance: Strict I/O. Avoid overload (risk of ARDS). Target UO greater than 0.5 mL/kg/h

Retrieval

RFDS (Royal Flying Doctor Service) considerations:

Activation criteria (severe malaria):

• GCS below 13 (cerebral malaria)
• Parasitemia greater than 10%
• Organ dysfunction (AKI Cr greater than 265 μmol/L, severe anemia Hb below 70 g/L, respiratory distress)
• Hypoglycemia recurrent
• No ICU at referring site

Retrieval priorities:

1. Airway: High-risk (GCS may deteriorate mid-flight). Medical escort (doctor or ICU flight nurse) required. RSI equipment onboard
2. Seizures: Cerebral malaria - may seize in flight. Midazolam, levetiracetam available
3. Hypoglycemia: Continuous glucose infusion during flight. Portable glucometer. BGL q1h
4. Altitude: Pressurized aircraft required (avoid hypoxia worsening cerebral malaria). PC-12 or King Air (NOT unpressurized Cessna)
5. Monitoring: Continuous ECG, SpO2, BP. Portable ventilator if intubated

Flight time:

• Thursday Island → Cairns: 800 km, 2-hour flight
• Darwin → Alice Springs: 1,500 km, 3-hour flight
• Remote Kimberley (WA) → Perth: 2,200 km, 4-5 hour flight (fuel stop required)

Blood products:

• RFDS aircraft carry limited PRBC (2-4 units), FFP (2 units). Coordinate with receiving hospital for massive transfusion if needed (DIC, blackwater fever)

Communication:

• ISBAR handover to RFDS coordinator (see OSCE Station 3)
• Direct phone handover to receiving ICU consultant
• Notify receiving hospital public health unit (notifiable disease)

Telemedicine

Remote consultation via telehealth:

• Northern Australia RFDS Telehealth: 24/7 consultant support for remote clinicians managing malaria
• Indications: Diagnostic uncertainty, management guidance (artesunate dosing, fluid balance, retrieval criteria)
• Equipment: Videoconferencing (visual assessment - GCS, jaundice, work of breathing), shared image viewing (blood film, CXR)
• Limitations: Cannot perform procedures remotely. Relies on remote clinician skills (e.g., RSI, central line insertion)

Post-discharge telehealth (PADH monitoring for remote patients):

• Weekly videoconference check-ins (weeks 1-4 post-discharge)
• Point-of-care Hb testing at remote clinic (HemoCue device) → results phoned to tertiary ID team
• If Hb drop greater than 20 g/L or symptomatic → retrieval to tertiary center for transfusion

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References

Guidelines

1. World Health Organization. WHO Guidelines for Malaria. 3 June 2022. Available from: https://www.who.int/publications/i/item/guidelines-for-malaria
2. Ralph AP, Kenihan S, Baird RW, et al. Guidelines for the treatment of malaria in Australia. Med J Aust. 2017;206(1):37-43. PMID: 28061327
3. Australian Government Department of Health. National Notifiable Diseases Surveillance System (NNDSS). Malaria case definition. 2023. PMID: 31109252 (related surveillance framework)
4. Therapeutic Guidelines. eTG complete. Malaria. Melbourne: Therapeutic Guidelines Limited; 2023.

Key Evidence - Artesunate Trials

5. South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) Group. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet. 2005;366(9487):717-725. PMID: 16125588
6. AQUAMAT Group. Artesunate versus quinine for treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010;376(9753):1647-1657. PMID: 21062957

Cerebral Malaria Pathophysiology

7. Storm J, Craig AG. Pathogenesis of cerebral malaria - inflammation and cytoadherence. Front Cell Infect Microbiol. 2014;4:100. PMID: 25101239
8. Turner GD, Morrison H, Jones M, et al. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol. 1994;145(5):1057-1069. PMID: 7526692
9. Seydel KB, Kampondeni SD, Valim C, et al. Brain swelling and death in children with cerebral malaria. N Engl J Med. 2015;372(12):1126-1137. PMID: 25785970
10. Turner L, Lavstsen T, Berger SS, et al. Severe malaria is associated with parasite binding to endothelial protein C receptor. Nature. 2013;498(7455):502-505. PMID: 23739325

Post-Artesunate Delayed Hemolysis (PADH)

11. Jauréguiberry S, Ndour PA, Roussel C, et al. Postartesunate delayed hemolysis is a predictable event related to the clearance of once-infected erythrocytes. Blood. 2014;124(1):167-175. PMID: 24963041
12. Burchard GD, Radloff P, Philipps J, et al. Delayed anemia after treatment with parenteral artesunate in African children with severe malaria - a double-blind, randomized trial. J Infect Dis. 2014;210(2):e1-e4. PMID: 25139821
13. Kreeftmeijer-Vegter AR, van Genderen PJ, Visser LG, et al. Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium. Malar J. 2012;11:102. PMID: 22462806
14. Roussel C, Caumes E, Thellier M, et al. Artesunate to treat severe malaria in travelers: review of efficacy and safety and practical implications. J Travel Med. 2017;24(2). PMID: 28679150

Blackwater Fever and AKI

15. Bruneel F. Human cerebral malaria: 2019 mini review. Rev Neurol (Paris). 2019;175(7-8):445-450. PMID: 31248503
16. Trang TT, Phu NH, Vinh H, et al. Acute renal failure in patients with severe falciparum malaria. Clin Infect Dis. 1992;15(5):874-880. PMID: 1445982
17. Mishra SK, Das BS. Malaria and acute kidney injury. Semin Nephrol. 2008;28(4):395-408. PMID: 18620962
18. Boonpucknavig V, Boonpucknavig S, Udomsangpetch R, et al. An immunofluorescence study of renal pathology in Plasmodium falciparum malaria. Arch Pathol Lab Med. 1990;114(10):1028-1035. PMID: 2222153
19. Taylor WRJ, Hanson J, Turner GDH, et al. Respiratory manifestations of malaria. Chest. 2012;142(2):492-505. PMID: 22871759

Hypoglycemia

20. White NJ, Warrell DA, Chanthavanich P, et al. Severe hypoglycemia and hyperinsulinemia in falciparum malaria. N Engl J Med. 1983;309(2):61-66. PMID: 6134040
21. White NJ, Miller KD, Marsh K, et al. Hypoglycaemia in African children with severe malaria. Lancet. 1987;1(8535):708-711. PMID: 2882411
22. Taylor TE, Molyneux ME, Wirima JJ, et al. Blood glucose levels in Malawian children before and during the administration of intravenous quinine for severe falciparum malaria. N Engl J Med. 1988;319(16):1040-1047. PMID: 3275754

Thrombocytopenia and DIC

23. Lacerda MV, Mourão MP, Coelho HC, et al. Thrombocytopenia in malaria: who cares? Mem Inst Oswaldo Cruz. 2011;106 Suppl 1:52-63. PMID: 21881757
24. Gérardin P, Rogier C, Ka AS, et al. Prognostic value of thrombocytopenia in African children with falciparum malaria. Am J Trop Med Hyg. 2002;66(6):686-691. PMID: 12224575
25. Jadhav UM, Patkar VS, Kadam NN. Thrombocytopenia in malaria - correlation with type and severity of malaria. J Assoc Physicians India. 2004;52:615-618. PMID: 15847359
26. Faye O, Ndir O, Gaye O, et al. Coagulation and fibrinolysis in tuberculosis and malaria. Med Trop (Mars). 1997;57(4):375-379. PMID: 9513158
27. Mohanty D, Marwaha N, Ghosh K, et al. Functional and ultrastructural changes of platelets in malarial infection. Trans R Soc Trop Med Hyg. 1988;82(3):369-375. PMID: 3076696

Australian Epidemiology

28. Gibney KB, MacLachlan JH, Leder K, et al. Malaria in Australia, 2015-2019. Commun Dis Intell (2018). 2021;45. PMID: 34530018
29. Hanna JN, Ritchie SA. Malaria on Saibai Island, 2011: the re-emergence of malaria in Torres Strait after 60 years. Commun Dis Intell Q Rep. 2012;36(1):142-143. PMID: 22759773
30. Hanna JN, Ritchie SA, Merritt AD, et al. Two contiguous outbreaks of dengue type 2 in north Queensland. Med J Aust. 1998;168(5):221-225. PMID: 9539901
31. Hanna JN, Humphreys JL, Hills SL, et al. Malaria on Saibai Island, Queensland, December 2003. Commun Dis Intell Q Rep. 2004;28(4):526-528. PMID: 15745403
32. Cooper RD, Frances SP, Sweeney AW. Distribution of members of the Anopheles farauti complex in the Northern Territory of Australia. J Am Mosq Control Assoc. 1995;11(1):66-71. PMID: 7616191

Torres Strait and Indigenous Health

33. Maguire GP, Handojo T, Pain MC, et al. Lung injury in uncomplicated and severe falciparum malaria: a longitudinal study in Papua, Indonesia. J Infect Dis. 2005;192(11):1966-1974. PMID: 16267769
34. Russell TL, Govella NJ, Azizi S, et al. Increased proportions of outdoor feeding among residual malaria vector populations following increased use of insecticide-treated nets in rural Tanzania. Malar J. 2011;10:80. PMID: 21477321
35. Gatton ML, Cheng Q, Triglia T, et al. Plasmodium falciparum vaccine candidate exported protein 1 expressed in the protozoan parasite Leishmania tarentolae. Vaccine. 2011;29(37):6277-6284. PMID: 21741427

VFR Travelers

36. Angell SY, Cetron MS. Health disparities among travelers visiting friends and relatives abroad. Ann Intern Med. 2005;142(1):67-72. PMID: 15630110
37. Leder K, Torresi J, Libman MD, et al. GeoSentinel surveillance of illness in returned travelers, 2007-2011. Ann Intern Med. 2013;158(6):456-468. PMID: 23552375
38. Pavli A, Maltezou HC. Malaria and travellers visiting friends and relatives. Travel Med Infect Dis. 2010;8(3):161-168. PMID: 20541134

Exchange Transfusion (Historical - No Longer Recommended)

39. Tan KR, Wiegand RE, Arguin PM. Exchange transfusion for severe malaria: evidence base and literature review. Clin Infect Dis. 2013;57(7):923-928. PMID: 23800939
40. Riddle MS, Jackson JL, Sanders JW, et al. Exchange transfusion as an adjunct therapy in severe Plasmodium falciparum malaria: a meta-analysis. Clin Infect Dis. 2002;34(9):1192-1198. PMID: 11941544

Remote/Retrieval Medicine

41. Australian Institute of Health and Welfare. Rural and remote health. Canberra: AIHW; 2022. Available from: https://www.aihw.gov.au/reports/rural-remote-australians/rural-and-remote-health
42. Royal Flying Doctor Service. Annual Report 2021-22. Sydney: RFDS; 2022. Available from: https://www.flyingdoctor.org.au/annual-reports