Complicated (Severe) Malaria

Introduction

Complicated or severe malaria is a medical emergency defined by the presence of asexual parasitemia with one or more life-threatening complications. While Plasmodium falciparum is the primary cause of severe malaria, P. vivax and P. knowlesi are increasingly recognized as causes of severe disease. Without prompt and appropriate treatment, the mortality rate is approximately 20%.

Pathophysiology

The pathogenesis involves a complex interplay of parasite and host factors:

• Cytoadherence and Sequestration: P. falciparum infected red blood cells (iRBCs) develop "knobs" on their surface, allowing them to adhere to the vascular endothelium of deep organs (brain, kidneys, lungs). This prevents the clearance of iRBCs by the spleen and causes microvascular obstruction, leading to tissue anoxia and organ dysfunction.
• Rosetting: The clumping of uninfected RBCs to iRBCs further blocks blood flow.
• Cytokine Storm: Rupture of schizonts releases toxins that stimulate the excessive production of pro-inflammatory cytokines (e.g., TNF-alpha, IL-1). These mediators drive fever, hypoglycemia, bone marrow suppression, and tissue injury.
• ** hemolysis:** Extensive destruction of both infected and uninfected RBCs leads to severe anemia.

Clinical Features and Diagnostic Criteria

The World Health Organization (WHO) defines severe malaria by the presence of P. falciparum (or P. vivax/P. knowlesi) parasitemia plus any one of the following criteria:

• Impaired Consciousness (Cerebral Malaria): Unarousable coma (Glasgow Coma Scale <11 in adults or Blantyre Coma Score <3 in children) not attributable to other causes (e.g., hypoglycemia, meningitis).
• Severe Anemia: Hemoglobin <5 g/dL (or hematocrit <15%) in children <12 years.
• Respiratory Distress (Acidosis): Deep, labored, acidotic breathing (Kussmaul’s respiration). Metabolic acidosis is a major predictor of mortality.
• Hypoglycemia: Blood glucose <40 mg/dL (<2.2 mmol/L). This is common in children and pregnant women and carries a poor prognosis.
• Multiple Convulsions: More than two episodes within 24 hours.
• Shock (Algid Malaria): Capillary refill ≥3 seconds, temperature gradient on limbs, or systolic BP <70 mm Hg in children.
• Acute Kidney Injury: Plasma creatinine >3 mg/dL or urea >20 mmol/L.
• Clinical Jaundice: Bilirubin >3 mg/dL combined with other organ dysfunction or high parasitemia.
• Hyperparasitemia: >10% of RBCs infected.
• Abnormal Bleeding: Disseminated Intravascular Coagulation (DIC) manifesting as bleeding from gums, nose, or venepuncture sites.
• Hemoglobinuria: Macroscopic dark urine ("Blackwater fever"), often associated with intravascular hemolysis.

Management

Severe malaria requires immediate hospitalization, preferably in an intensive care unit (ICU).

1. General Supportive Care

• Airway & Breathing: Secure airway in comatose patients; administer oxygen for respiratory distress.
• Circulation: Treat shock with careful fluid resuscitation. Avoid fluid overload to prevent pulmonary edema.
• Monitoring: Monitor blood glucose every 4 hours, vital signs, and coma score.

2. Specific Antimalarial Therapy

Parenteral therapy is mandatory as oral bioavailability is unpredictable in severe illness.

• Drug of Choice: Intravenous (IV) Artesunate.
  • Dose: 2.4 mg/kg IV at 0, 12, and 24 hours, then once daily.
  • Efficacy: Reduces mortality by ~25% compared to quinine and has a better safety profile.
  • Note: Monitor for delayed hemolytic anemia 1–4 weeks after treatment.
• Alternative: IV Quinine.
  • Dose: Loading dose of 20 mg salt/kg infused over 4 hours, followed by maintenance of 10 mg salt/kg every 8 hours.
  • Precautions: Requires cardiac monitoring for QT prolongation and arrhythmias. Monitor glucose closely as quinine stimulates insulin release, causing hypoglycemia.
• Follow-up: Once the patient can tolerate oral medication (and usually after at least 24 hours of parenteral therapy), switch to a full course of an oral Artemisinin-based Combination Therapy (ACT) like Artemether-Lumefantrine.

3. Management of Complications

• Hypoglycemia: Correct immediately with IV dextrose (e.g., 2–5 mL/kg of 10% dextrose).
• Seizures: Treat with IV Benzodiazepines (Diazepam 0.3–0.5 mg/kg or Lorazepam 0.1 mg/kg). If persistent, use Phenytoin or Phenobarbitone.
• Severe Anemia: Transfuse packed red blood cells (10 mL/kg) if Hb <5 g/dL (or <7 g/dL in the presence of respiratory distress).
• Blackwater Fever: Discontinue offending drugs (like quinine if suspected) and manage acute kidney injury, potentially requiring dialysis.

4. Adjunctive Therapies

• Contraindicated: Corticosteroids, heparin, and prophylactic phenobarbitone have been shown to be harmful or of no benefit.
• Exchange Transfusion: Currently not recommended based on lack of survival benefit in recent analyses.