Acute falciparum malaria is associated with low plasma arginine and impaired nitric oxide (NO) production. Both are associated with poor outcome. This study will examine the safety and effect of escalating doses of arginine in falciparum malaria. It will determine whether arginine can increase NO production and have an effect on NO-dependent physiological measurements. The hypothesis is that arginine: will be safe in falciparum malaria; will return plasma arginine concentration to normal/supranormal levels; will increase systemic and exhaled NO; reduces oxidant stress; and improves a number of NO-dependent physiological measures of relevance to malaria.

Inclusion Criteria:

1. Ages 18-60 years
2. P. falciparum parasitemia (1,000-100,000 parasites/ul).
3. Clinical syndrome consistent with malaria associated with documented fever (axillary temperature > 38℃) or self-reported history of fever in the last 48 hours with no other cause present
4. Commenced oral quinine ≤ 18 hours prior to scheduled commencement of arginine
5. An indication for hospital admission (eg relative cannot look after/supervise treatment at home but not having any warning signs or severe malaria criteria in "exclusion criteria" below)
6. Informed consent obtained

Exclusion Criteria:

1. Pregnancy or lactation

2. Mixed infection with P. falciparum and P. vivax

3. Warning signs of altered mental state and inability to sit unaided

4. Features of severe/complicated malaria

5. Diabetes

6. Systolic blood pressure (BP) < 100 mmHg

7. Serious underlying disease (cardiac, hepatic, kidney)

8. Initial iSTAT test showing any of the following values:

   • glucose < 4 mmol/L;
   • K+ ≥ 4.2 meq/L;
   • Cl- > 106 meq/L;
   • HCO3- < 20 meq/L.

9. Known allergy to L-arginine

10. Concurrent therapy with any of the following medications:

    • spironolactone;
    • oral nitrates;
    • phosphodiesterase inhibitor (eg sildenafil [Viagra]);
    • alpha-blocking antihypertensive agents (eg prazosin);
    • L-arginine.