Which baseline and follow‑up investigations should be ordered for a patient with severe Plasmodium falciparum malaria receiving intravenous artesunate?

Baseline and Follow-Up Investigations for Severe Plasmodium falciparum Malaria Treated with IV Artesunate

For patients with severe P. falciparum malaria receiving intravenous artesunate, immediately obtain thick blood film, hemoglobin, blood glucose, renal function, liver function, lactate, and blood gas analysis at baseline, then monitor parasitemia every 12 hours until <1%, followed by every 24 hours until negative, with mandatory surveillance for post-artesunate delayed hemolysis at days 7,14,21, and 28. 1

Baseline Investigations (Immediate Upon Admission)

Essential Diagnostic Tests

• Thick blood film for parasitemia quantification 2
• Hemoglobin/complete blood count to assess for severe anemia (Hb <7 g/dL) 2
• Blood glucose to detect hypoglycemia (<40 mg/dL or 2.2 mmol/L), a critical complication associated with fatal outcomes 2
• Renal function (creatinine >3 mg/dL or >265 mmol/L indicates severe malaria) 2
• Liver function tests including total bilirubin (>3 mg/dL with parasite count >100,000/mL indicates severe disease) and ALT 2
• Blood gas analysis to assess acidosis (pH <7.35 or bicarbonate <15 mmol/L) and lactate levels (>5 mmol/L indicates hyperlactatemia) 2, 1

Additional Baseline Tests

• Blood grouping and cross-matching if hemoglobin is below 4 g/dL (or <6 g/dL with heart failure signs) 2
• Lumbar puncture in patients with altered consciousness or repeated convulsions to exclude bacterial meningitis 2

Parasitemia Monitoring During Treatment

Frequency and Targets

• Every 12 hours until parasitemia declines to <1% of red blood cells 2, 1, 3
• Every 24 hours once <1% is achieved, continuing until negative 2, 1, 3
• An initial increase in parasite density within the first 24 hours does not indicate treatment failure 1, 3

Critical caveat: Do not switch from IV artesunate to oral therapy until parasitemia falls below 1%, even if the patient appears clinically improved. 1

Daily Monitoring of Physiological Parameters

Metabolic and Organ Function

• Blood glucose monitoring continuously, as hypoglycemia is a major risk factor for mortality and can occur at any time during treatment 2, 1
• Plasma bicarbonate and lactate levels to track resolution of acidosis 1
• Renal function (creatinine, urine output) daily to detect acute kidney injury 2
• Liver function tests daily to monitor improvement 2
• Complete blood count daily to assess anemia progression 2

Continuous Clinical Monitoring

• Cardiocirculatory parameters (blood pressure, heart rate) 1
• Pulmonary status (respiratory rate, oxygen saturation) to detect pulmonary edema or ARDS 1
• Neurological status (Glasgow Coma Scale) in patients with cerebral malaria 2

Post-Treatment Surveillance: Post-Artesunate Delayed Hemolysis (PADH)

Mandatory Follow-Up Schedule

Post-artesunate delayed hemolysis occurs in approximately 10-15% of patients treated with IV artesunate and requires systematic surveillance. 1, 3

• Day 7: Hemoglobin, haptoglobin, lactate dehydrogenase 1, 3, 4
• Day 14: Hemoglobin, haptoglobin, lactate dehydrogenase 1, 3, 4
• Day 21: Hemoglobin, haptoglobin, lactate dehydrogenase 1, 3, 4
• Day 28: Hemoglobin, haptoglobin, lactate dehydrogenase 1, 3, 4

Critical pitfall: Do not delay PADH monitoring; complications can arise up to four weeks post-treatment, particularly in patients with initial hyperparasitemia (>10%). 1, 4 The risk is highest in those with parasitemia levels of 14-21% at presentation. 4

Common Pitfalls to Avoid

• Do not stop parasitemia monitoring once the patient appears clinically improved; continue until negative results are confirmed 1
• Do not assume adequate parasite clearance based solely on clinical improvement; laboratory confirmation of <1% parasitemia is mandatory before transitioning to oral therapy 1, 3
• Do not omit post-discharge follow-up for PADH surveillance; this complication is delayed and can be clinically significant, requiring transfusion in some cases 4
• Do not overlook hypoglycemia monitoring in patients receiving IV artesunate, as it remains a critical complication even with superior antimalarial efficacy compared to quinine 2, 5