Fewer doses of malaria drug just as effective

Child in Thies, Senegal

Photo by Sarah Mattison

A trial of African children suggests that 3 doses of artesunate can be just as effective as 5 doses for treating severe malaria.

A 3-dose intramuscular (IM) artesunate regimen proved noninferior to 5 doses of IM artesunate.

However, a 3-dose intravenous (IV) artesunate regimen was not as effective.

Peter Kremsner, MD, of Eberhard Karls Universität Tübingen in Germany, and his colleagues reported these results in PLOS Medicine.

The World Health Organization recommends that patients with severe malaria be given a 5-dose regimen of IV or IM artesunate at the time of admission (0 hours) and at 12, 24, 48, and 72 hours. However, in resource-limited settings, administering 5 doses on schedule can be challenging.

So Dr Kremsner and his colleagues wanted to determine if 3 doses of artesunate would be just as effective. They conducted an open-label, randomized, controlled trial investigating the efficacy of 3-dose IV or IM artesunate at 0, 24, and 48 hours.

The researchers enrolled 1047 children (0.5 to 10 years of age) who had severe malaria and were treated at 7 different sites in 5 African countries. The children were randomized to receive a total artesunate dose of 12 mg/kg as a control regimen of 5 IM injections (n=348) or 3 injections of 4 mg/kg either IM (n=348) or IV (n=351).

Of these children, 1002 received treatment per-protocol—331 in the 5-dose group, 338 in the 3-dose IM group, and 333 in the 3-dose IV group.

Seventy-eight percent of patients in the 3-dose IM group had about 99% parasite clearance at 24 hours, as did 79% of patients in the 5-dose IM group, a result that met a preset criterion for noninferiority (P=0.02).

However, the 3-dose IV regimen did not meet the noninferiority criterion. Seventy-four percent of these children had about 99% parasite clearance at 24 hours (P=0.24).

Twenty-two percent of the entire study population developed delayed anemia, but there was no difference in the incidence of this adverse event between the treatment arms.

The researchers said further studies are needed to clarify whether treatment with artesunate or the malaria infection itself was responsible for the delayed anemia. And patients receiving the drug should be monitored for this complication.

The team also said their findings suggest a 3-dose IM artesunate regimen can be effective against severe malaria in children, but this study did have limitations. For instance, due to practical constraints, the primary endpoint was parasite clearance at 24 hours rather than survival.

Child in Thies, Senegal

Photo by Sarah Mattison

A trial of African children suggests that 3 doses of artesunate can be just as effective as 5 doses for treating severe malaria.

A 3-dose intramuscular (IM) artesunate regimen proved noninferior to 5 doses of IM artesunate.

However, a 3-dose intravenous (IV) artesunate regimen was not as effective.

Peter Kremsner, MD, of Eberhard Karls Universität Tübingen in Germany, and his colleagues reported these results in PLOS Medicine.

The World Health Organization recommends that patients with severe malaria be given a 5-dose regimen of IV or IM artesunate at the time of admission (0 hours) and at 12, 24, 48, and 72 hours. However, in resource-limited settings, administering 5 doses on schedule can be challenging.

So Dr Kremsner and his colleagues wanted to determine if 3 doses of artesunate would be just as effective. They conducted an open-label, randomized, controlled trial investigating the efficacy of 3-dose IV or IM artesunate at 0, 24, and 48 hours.

The researchers enrolled 1047 children (0.5 to 10 years of age) who had severe malaria and were treated at 7 different sites in 5 African countries. The children were randomized to receive a total artesunate dose of 12 mg/kg as a control regimen of 5 IM injections (n=348) or 3 injections of 4 mg/kg either IM (n=348) or IV (n=351).

Of these children, 1002 received treatment per-protocol—331 in the 5-dose group, 338 in the 3-dose IM group, and 333 in the 3-dose IV group.

Seventy-eight percent of patients in the 3-dose IM group had about 99% parasite clearance at 24 hours, as did 79% of patients in the 5-dose IM group, a result that met a preset criterion for noninferiority (P=0.02).

However, the 3-dose IV regimen did not meet the noninferiority criterion. Seventy-four percent of these children had about 99% parasite clearance at 24 hours (P=0.24).

Twenty-two percent of the entire study population developed delayed anemia, but there was no difference in the incidence of this adverse event between the treatment arms.

The researchers said further studies are needed to clarify whether treatment with artesunate or the malaria infection itself was responsible for the delayed anemia. And patients receiving the drug should be monitored for this complication.

The team also said their findings suggest a 3-dose IM artesunate regimen can be effective against severe malaria in children, but this study did have limitations. For instance, due to practical constraints, the primary endpoint was parasite clearance at 24 hours rather than survival.

Child in Thies, Senegal

Photo by Sarah Mattison

A trial of African children suggests that 3 doses of artesunate can be just as effective as 5 doses for treating severe malaria.

A 3-dose intramuscular (IM) artesunate regimen proved noninferior to 5 doses of IM artesunate.

However, a 3-dose intravenous (IV) artesunate regimen was not as effective.

Peter Kremsner, MD, of Eberhard Karls Universität Tübingen in Germany, and his colleagues reported these results in PLOS Medicine.

The World Health Organization recommends that patients with severe malaria be given a 5-dose regimen of IV or IM artesunate at the time of admission (0 hours) and at 12, 24, 48, and 72 hours. However, in resource-limited settings, administering 5 doses on schedule can be challenging.

So Dr Kremsner and his colleagues wanted to determine if 3 doses of artesunate would be just as effective. They conducted an open-label, randomized, controlled trial investigating the efficacy of 3-dose IV or IM artesunate at 0, 24, and 48 hours.

The researchers enrolled 1047 children (0.5 to 10 years of age) who had severe malaria and were treated at 7 different sites in 5 African countries. The children were randomized to receive a total artesunate dose of 12 mg/kg as a control regimen of 5 IM injections (n=348) or 3 injections of 4 mg/kg either IM (n=348) or IV (n=351).

Of these children, 1002 received treatment per-protocol—331 in the 5-dose group, 338 in the 3-dose IM group, and 333 in the 3-dose IV group.

Seventy-eight percent of patients in the 3-dose IM group had about 99% parasite clearance at 24 hours, as did 79% of patients in the 5-dose IM group, a result that met a preset criterion for noninferiority (P=0.02).

However, the 3-dose IV regimen did not meet the noninferiority criterion. Seventy-four percent of these children had about 99% parasite clearance at 24 hours (P=0.24).

Twenty-two percent of the entire study population developed delayed anemia, but there was no difference in the incidence of this adverse event between the treatment arms.

The researchers said further studies are needed to clarify whether treatment with artesunate or the malaria infection itself was responsible for the delayed anemia. And patients receiving the drug should be monitored for this complication.

The team also said their findings suggest a 3-dose IM artesunate regimen can be effective against severe malaria in children, but this study did have limitations. For instance, due to practical constraints, the primary endpoint was parasite clearance at 24 hours rather than survival.