South East Asian Quinine Artesunate Malaria Trial (Download article here.)

In my attempt to familiarize myself with the clinical management of malaria, I reviewed the SEAQUAMAT Study headed by Nick White’s group in Thailand. I’m reviewing the major points here, primarily so I can go back to it when needed:

Design: Multi-center, open-label, randomized controlled trial in Bangladesh, Myanmar, India, and Indonesia.

Inclusion criteria: Age > 2; Positive bloodstick for PfHRP2 Antigen; and severe malaria defined as:

1) malaria positive on blood smear

AND ONE OF THE FOLLOWING:

1) GCS less than 11/15 or Blantyre Coma Scale less than or equal to 3/5
2) Parasitemia greater than 10%
3) Glucose less than 2.2 mmol/L
4) HCT less than 20% and parasite load greater than 100,000/ul
5) Jaundice and parasite load greater than 100,000/ul
6) bicarb less than 17 mmol/L
7) BUN greater than 15 mmol/L (mnemonic 15+17=32)
9) evidence of shock determined by clinician (low BP, cool extremities)

Note that the study was done with intention to treat analysis. Initial treatment was made on clinical grounds. Per protocol analysis was done after severe malaria was confirmed.

Treatment arms: artesunate IV 2.4 mg/kg bolus at 0, 12, 24 h and a once daily bolus thereafter until PO meds can be taken
quinine IV, 20 mg/kg infusion loading over the first 4 hours, then 10 mg/kg infusion over 2-8 hours three
times daily

Adverse effects: artesunate: well-tolerated
quinine: narrow therapeutic range, hyperinsulinemic hypoglycemia, can cause hypotension if infused
rapidly, IM injections are painful, cause sterile abscesses, and predisposes to tetanus.

Primary outcome: mortality
Secondary outcome: neurological sequelae, combined death and neurological sequelae, recovery times from neurological
sequelae and development of severe complications

Results: Artesunate (15% mortality, n=730)
Quinine (22% mortality, n=731) P = 0.0002
Overall mortality: 19%
Overall mortality of those found to have severe malaria: 24%
Mortality in the 202 chidren < 15 yo analysed: Artesunate 5% vs. Quinine 11%, P = 0.15

Conclusion: Artesunate is superior and safer for severe malaria in this Southeast Asian adults.

Reference: Lancet. 2005 Aug 27-Sep 2;366(9487):717-25.