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Infectious Diseases

Severe Malaria

A medical emergency where Plasmodium falciparum infection causes life-threatening manifestations due to vital organ dysfunction. Requires urgent parenteral antimalarial treatment and intensive supportive care.

Also known as: Complicated Malaria

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Referral and warning signs

When to refer

IMMEDIATE URGENT REFERRAL/ADMISSION to Hospital (H/RR with capacity for intensive monitoring/care) for ALL patients meeting criteria for severe malaria. If at lower facility, administer pre-referral treatment (Rectal Artesunate for children <6y; IM Artesunate/Artemether/Quinine if available for others) before transfer.

Red flags

  • Any WHO criterion for severe malaria (impaired consciousness, prostration, multiple seizures, respiratory distress, shock, jaundice, bleeding, dark urine, severe anaemia, hypoglycaemia, AKI, acidosis, hyperparasitaemia).

Signs and symptoms

  • Presence of P. falciparum asexual forms in blood PLUS one or more clinical or laboratory features of severity:
  • Clinical Manifestations:
  • - Impaired Consciousness / Coma: (Cerebral Malaria - GCS <11 in adults, Blantyre Coma Score <3 in children; unable to localize pain).
  • - Prostration: Generalized weakness, inability to sit, stand, or walk without assistance (or feed/drink in young children).
  • - Multiple Convulsions: More than two generalized seizures in 24 hours.
  • - Deep Breathing / Acidotic Breathing (Kussmaul): Sign of metabolic acidosis.
  • - Respiratory Distress (ARDS): Tachypnea, nasal flaring, chest retractions, pulmonary oedema (crackles).
  • - Circulatory Collapse / Shock: Systolic BP <80 mmHg (adults) or <50 mmHg (children <5y), with cold peripheries, slow capillary refill.
  • - Jaundice: Clinical icterus (yellow sclera/skin) PLUS evidence of other vital organ dysfunction.
  • - Abnormal Spontaneous Bleeding: (e.g., gums, nose, GI tract) +/- evidence of DIC.
  • - Haemoglobinuria: Dark or black urine (macroscopic).
  • Laboratory Manifestations:
  • - Severe Anaemia: Hb <5 g/dL (or Hct <15%) in children <12y; Hb <7 g/dL (or Hct <20%) in adults. Adjusted criteria for pregnancy.
  • - Hypoglycaemia: Blood glucose <2.2 mmol/L (40 mg/dL).
  • - Metabolic Acidosis: Plasma bicarbonate <15 mmol/L or Base Excess < -8 mEq/L (or high lactate).
  • - Acute Kidney Injury (AKI): Plasma creatinine >3.0 mg/dL (265 µmol/L) or Urine output <0.5 mL/kg/hr over 6-12 hours.
  • - Hyperlactatemia: Plasma lactate >5 mmol/L.
  • - Hyperparasitaemia: P. falciparum parasitaemia >10% (or >250,000/µL) in low transmission areas; >20% in high transmission areas (less reliable indicator alone).

Risk factors

  • P. falciparum infection.
  • Lack of immunity (young children <5y, travellers from non-endemic areas).
  • Pregnancy (especially primigravidae).
  • HIV co-infection.
  • Delayed or inadequate treatment of uncomplicated malaria.
  • Splenectomy.

Diagnosis

Clinical assessment

Presence of any sign/symptom of severity (as listed above) in a patient with confirmed P. falciparum malaria (RDT/Microscopy). Must rule out other causes of severe illness.

Differential diagnosis

  • Bacterial Meningitis / Encephalitis.
  • Sepsis / Septic shock.
  • Severe Pneumonia.
  • Typhoid fever (complicated).
  • Viral Haemorrhagic Fevers.
  • Leptospirosis.
  • DKA / Hypoglycaemic coma.
  • Poisoning.

Investigations

  • Parasitological Confirmation: RDT or Microscopy (essential). Quantify parasitaemia if possible.
  • Assess Severity Markers:
  • - Blood Glucose (Point-of-care essential).
  • - Haemoglobin / FBC.
  • - Renal function (Creatinine/Urea) & Electrolytes.
  • - Liver function tests (Bilirubin, AST/ALT).
  • - Blood Gas (Venous or Arterial) - assess acidosis (pH, Bicarb, Lactate).
  • - Coagulation screen (if bleeding).
  • Rule out other diagnoses: Lumbar Puncture (if coma/meningism and malaria test negative or low parasitaemia), Blood culture, Chest X-ray, Urinalysis.
  • Monitor urine output (catheterize if needed).

Diagnostic criteria

Confirmed P. falciparum infection + >=1 WHO clinical or laboratory criterion for severe malaria.

Management

Non-pharmacological management

  • Urgent Hospital Admission (preferably ICU/High Dependency Unit).
  • Airway, Breathing, Circulation (ABC) Support:
  • - Secure airway if comatose/seizing.
  • - Oxygen therapy for hypoxia/respiratory distress.
  • - Mechanical ventilation if needed.
  • - IV fluid resuscitation for shock/dehydration (use cautiously to avoid fluid overload/pulmonary oedema). Monitor closely.
  • Intensive Nursing Care: Monitor vital signs, GCS, SpO2, blood glucose, fluid balance frequently. Seizure precautions. Prevent pressure sores.
  • Nutritional support (NGT if needed, once stable).

Pharmacological treatment

  • Parenteral Antimalarial Treatment (IMMEDIATE):
  • - First Line: Intravenous (IV) Artesunate. Preferred treatment for all ages.
  • - Dose: 2.4 mg/kg IV bolus given at 0h, 12h, 24h, then once daily. (Child <20kg use 3.0 mg/kg dose).
  • - Give for minimum 24h AND until patient can tolerate full course of oral ACT.
  • - Switch to full 3-day course of oral ACT (e.g., AL, DHA-PPQ) as soon as tolerated.
  • - If IV access difficult/delayed, give first dose IM while establishing IV line.
  • - Alternatives (if IV Artesunate unavailable):
  • - Intramuscular (IM) Artemether: Loading dose 3.2 mg/kg IM, then 1.6 mg/kg IM daily. Switch to oral ACT when tolerated.
  • - Intravenous (IV) Quinine: Loading dose 20mg quinine salt/kg IV infusion over 4h, then maintenance 10mg salt/kg IV infusion over 4h Q8H. Requires cardiac monitoring, careful infusion rate control (risk of hypotension, arrhythmia, hypoglycaemia). Switch to oral ACT/Quinine when tolerated.
  • Management of Complications: (See UCG table p.175-176)
  • - Convulsions: IV/Rectal Diazepam OR IV Phenobarbital.
  • - Hypoglycaemia: IV Dextrose (10% for children, 25-50% for adults). Monitor glucose frequently.
  • - Severe Anaemia: Blood transfusion (Packed cells 10-15ml/kg or Whole blood 20ml/kg).
  • - Pulmonary Oedema / ARDS: Fluid restriction, Oxygen, Frusemide, Ventilatory support.
  • - Acute Kidney Injury: Fluid management, avoid nephrotoxins, consider dialysis if available.
  • - Metabolic Acidosis: Treat underlying cause (malaria, shock, hypoxia), fluid resuscitation, consider bicarbonate if severe (pH<7.2).
  • - Bacterial Co-infection: Add broad-spectrum antibiotics if sepsis suspected.
  • - Shock: Fluid boluses (cautiously), consider vasopressors (ICU).
  • Adjunctive Therapies: Routine use of steroids, heparin, mannitol, adrenaline is NOT recommended and may be harmful.

Monitoring

Continuous/frequent monitoring of vital signs, GCS, SpO2, blood glucose, urine output, fluid balance. Monitor parasitaemia daily until cleared. Monitor Hb, renal function, electrolytes. Monitor for complications.

Complications

  • Cerebral Malaria -> Coma, seizures, neurological sequelae.
  • Severe Anaemia.
  • Respiratory Distress / ARDS.
  • Hypoglycaemia.
  • Acute Kidney Injury.
  • Metabolic Acidosis.
  • Circulatory Collapse / Shock.
  • Spontaneous Bleeding / DIC.
  • Haemoglobinuria ('Blackwater Fever').
  • Secondary bacterial infections.
  • Post-malaria neurological syndrome (rare).
  • Death.

Prevention

  • Same as for uncomplicated malaria (LLINs, IRS, prompt treatment, IPTp, etc.).
  • Early recognition and effective treatment of uncomplicated malaria prevents progression to severe disease.

Patient education

  • Explanation of severe malaria as a life-threatening condition.
  • Need for urgent hospitalization and intensive treatment (IV/IM medication).
  • Importance of completing full course of treatment (parenteral followed by oral ACT).
  • Potential complications.
  • Importance of prevention measures (bed nets) upon discharge.

Uganda-specific notes

Severe malaria remains a major cause of hospitalization and death, especially in children <5y. IV Artesunate is the recommended first-line treatment. Pre-referral treatment with rectal artesunate (children <6y) or IM artesunate/artemether is crucial where referral is needed. Management of complications is challenging with limited resources.

References

  • Uganda Clinical Guidelines (UCG) 2023

    Chapter 2, Section 2.5.2.2, 2.5.2.3

  • Consolidated Guidelines for the Prevention and Treatment of Malaria in Uganda

    (Latest MOH Malaria Guidelines)

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