In the Journals

Modifications to P. vivax malaria therapy reduce recurrences

A “modest” increase in the WHO-recommended target dose of chloroquine for Plasmodium vivax malaria reduced more than 40% of recurrences among children younger than 5 years of age, according to findings from a recent systematic review and meta-analysis published in The Lancet Infectious Diseases.

Robert J. Commons, FRACP, of the WorldWide Antimalarial Resistance Network, and colleagues also found that the addition of primaquine further reduced recurrences by 90% compared with chloroquine alone.

“As reports of chloroquine treatment failure for P. vivax increase, we recommend that the dose of chloroquine be increased to 30 mg/kg in children younger than 5 years, and health care providers should be encouraged to provide adjunctive primaquine radical therapy to reduce the risk of both recrudescent and relapsing infections,” the researchers wrote.

Chloroquine-resistant P. vivax first emerged in 1989 and is now reported in most endemic countries, highlighting the need for alternative treatment strategies, according to Commons and colleagues. In countries with high levels of chloroquine resistance, national guidelines now recommend the use of artemisinin combination therapy for all malaria species. In other countries, chloroquine can be optimized by increasing the dose or duration, or by adding primaquine, which provides additional blood schizontocidal activity to prevent P. vivax relapses, the researchers reported.

To investigate the effects of treatment modification, Commons and colleagues analyzed data from 37 studies published between January 2000 and March 2017 that examined the efficacy of various chloroquine doses with or without primaquine. Their analysis included 5,240 participants in 17 countries. The primary outcome was the rate of recurrence between days 7 and 42.

Overall, 57.1% of patients received chloroquine monotherapy and 34.8% received a chloroquine dose lower than the WHO-recommended target of 25 mg/kg. By day 42, the risk for recurrence among all participants was 32.4% (95% CI, 29.8-35.1). Increasing chloroquine by 5 mg/kg reduced recurrences by more than 40% (adjusted HR = 0.82; 95% CI, 0.69-0.97). The benefit of the 30 mg/kg dose was greatest in children younger than 5 years of age (aHR = 0.59; 95% CI, 0.41-0.86), the researchers said.

The addition of primaquine reduced the risk to 4.9% (95% CI, 3.1-7.7), which was less than chloroquine alone (aHR = 0.10; 95% CI, 0.05-0.17).

A comprehensive safety analysis was not conducted; however, Commons and colleagues said there are substantial data supporting the safety of the 30 mg/kg dose in children. In addition, the risk for vomiting in the current analysis was low and not associated with chloroquine dose.

In a related editorial, Georges Snounou, PhD, research director at the National Center for Scientific Research in Paris, said health care providers should consider increasing the 25 mg/kg chloroquine dose.

“The minimal costs incurred will surely be outweighed by the resulting health and socioeconomic benefits,” he wrote.

But Snounou warned the high rates of chloroquine monotherapy in P. vivax-endemic regions were “concerning” and the study results “should not be taken as advocating this regimen.”

“With P. vivax malaria now firmly in sight of the malaria control community, and in view of the rising number of endemic areas where chloroquine resistance is recorded, the malaria community needs to prioritize research leading to the universal implementation of efficacious combination therapies for P. vivax that incorporate an anti-hypnozoicidal partner,” he wrote. “The threat of P. vivax endemicity is unlikely to disappear until radical cure becomes the usual treatment outcome.” – by Stephanie Viguers

Disclosures: Commons and Snounou report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

A “modest” increase in the WHO-recommended target dose of chloroquine for Plasmodium vivax malaria reduced more than 40% of recurrences among children younger than 5 years of age, according to findings from a recent systematic review and meta-analysis published in The Lancet Infectious Diseases.

Robert J. Commons, FRACP, of the WorldWide Antimalarial Resistance Network, and colleagues also found that the addition of primaquine further reduced recurrences by 90% compared with chloroquine alone.

“As reports of chloroquine treatment failure for P. vivax increase, we recommend that the dose of chloroquine be increased to 30 mg/kg in children younger than 5 years, and health care providers should be encouraged to provide adjunctive primaquine radical therapy to reduce the risk of both recrudescent and relapsing infections,” the researchers wrote.

Chloroquine-resistant P. vivax first emerged in 1989 and is now reported in most endemic countries, highlighting the need for alternative treatment strategies, according to Commons and colleagues. In countries with high levels of chloroquine resistance, national guidelines now recommend the use of artemisinin combination therapy for all malaria species. In other countries, chloroquine can be optimized by increasing the dose or duration, or by adding primaquine, which provides additional blood schizontocidal activity to prevent P. vivax relapses, the researchers reported.

To investigate the effects of treatment modification, Commons and colleagues analyzed data from 37 studies published between January 2000 and March 2017 that examined the efficacy of various chloroquine doses with or without primaquine. Their analysis included 5,240 participants in 17 countries. The primary outcome was the rate of recurrence between days 7 and 42.

Overall, 57.1% of patients received chloroquine monotherapy and 34.8% received a chloroquine dose lower than the WHO-recommended target of 25 mg/kg. By day 42, the risk for recurrence among all participants was 32.4% (95% CI, 29.8-35.1). Increasing chloroquine by 5 mg/kg reduced recurrences by more than 40% (adjusted HR = 0.82; 95% CI, 0.69-0.97). The benefit of the 30 mg/kg dose was greatest in children younger than 5 years of age (aHR = 0.59; 95% CI, 0.41-0.86), the researchers said.

The addition of primaquine reduced the risk to 4.9% (95% CI, 3.1-7.7), which was less than chloroquine alone (aHR = 0.10; 95% CI, 0.05-0.17).

A comprehensive safety analysis was not conducted; however, Commons and colleagues said there are substantial data supporting the safety of the 30 mg/kg dose in children. In addition, the risk for vomiting in the current analysis was low and not associated with chloroquine dose.

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In a related editorial, Georges Snounou, PhD, research director at the National Center for Scientific Research in Paris, said health care providers should consider increasing the 25 mg/kg chloroquine dose.

“The minimal costs incurred will surely be outweighed by the resulting health and socioeconomic benefits,” he wrote.

But Snounou warned the high rates of chloroquine monotherapy in P. vivax-endemic regions were “concerning” and the study results “should not be taken as advocating this regimen.”

“With P. vivax malaria now firmly in sight of the malaria control community, and in view of the rising number of endemic areas where chloroquine resistance is recorded, the malaria community needs to prioritize research leading to the universal implementation of efficacious combination therapies for P. vivax that incorporate an anti-hypnozoicidal partner,” he wrote. “The threat of P. vivax endemicity is unlikely to disappear until radical cure becomes the usual treatment outcome.” – by Stephanie Viguers

Disclosures: Commons and Snounou report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.