How can artesunate (ART) and quinine (QN) be given concomitantly?

From the Guidelines

Artesunate and quinine should not be given concomitantly as first-line treatment for severe malaria, instead, intravenous artesunate is the recommended first-line treatment. According to the most recent guidelines, intravenous artesunate is the drug of choice for severe malaria, including imported cases, due to its faster parasite clearance time and shorter ICU stay compared to quinine 1. The recommended regimen for artesunate is 3 doses, and once the patient is clinically improved, a switch to an oral artemisinin-based combination therapy (ACT) should be made, with the administration of a full course of the chosen drug. While quinine can be used, it is not the preferred first-line treatment due to the availability of artesunate, which has shown better outcomes in severe malaria cases 1.

Key points to consider when treating severe malaria include:

• Intravenous artesunate should be administered for 3 doses
• A switch to an oral ACT should be made once the patient is clinically improved
• Clinical complications of severe malaria should be managed by intensivists according to guidelines
• Restrictive fluid management is generally adopted to avoid pulmonary or cerebral oedema
• Acute kidney injury may benefit from a reno-protective effect of acetaminophen

It's essential to note that the use of artesunate and quinine concomitantly is not recommended as a first-line treatment, and the focus should be on using intravenous artesunate as the primary treatment for severe malaria, with a switch to oral ACT once the patient is clinically improved 1.

From the Research

Administration of Artesunate and Quinine

• Artesunate and quinine can be given concomitantly for the treatment of severe malaria, with artesunate being the preferred first-line treatment due to its higher efficacy and faster parasite clearance rate 2, 3.
• The standard treatment for severe malaria in Indonesia is intravenous artesunate followed by a full course of dihydroartemisinin-piperaquine, while quinine is used when standard therapy is not available 2.
• Studies have shown that artesunate is more effective than quinine in reducing the length of hospital stay and the risk of malaria recurrence within 28 days after hospital admission 2, 3.
• Rectal artesunate has been shown to be effective in the initial treatment of moderately severe malaria in African children and adults, with rapid reduction in parasite density within the first 24 hours of treatment 4.
• Comparison of artesunate and quinine in the treatment of Sudanese children with severe Plasmodium falciparum malaria showed no significant difference in fever, parasite clearance, and coma resolution times, but artesunate can be used as an alternative treatment 5.
• Rectal artemisinins, including artesunate, have been shown to be safe and effective in clearing parasites rapidly, with a single higher dose of rectal artesunate being more likely to achieve >90% parasite reductions at 24 hours 6.

Dosage and Administration

• The dosage of artesunate and quinine may vary depending on the specific treatment protocol and patient population, but typical dosages include intravenous artesunate 2.4 mg/kg at 0,12, and 24 hours, then daily, and intravenous quinine 20mg/kg initially then 10mg/kg three times a day 5.
• Rectal artesunate can be administered as a single dose of about 10 mg/kg, with a single higher dose being more effective in achieving rapid parasite clearance 4, 6.

Safety and Efficacy

• Artesunate and quinine have been shown to be safe and effective in the treatment of severe malaria, with artesunate being associated with a lower risk of adverse events and a faster parasite clearance rate 2, 3, 6.
• However, quinine has been associated with a higher risk of hypoglycaemia and other adverse events, and its use should be carefully monitored 5.