Radical Cure of P. vivax Malaria

Radical Cure of P. vivax Malaria

Plasmodium vivax, the dominant form of malaria
outside of Africa, can remain dormant in the liver after initial infection as the hypnozoite
stage and then reactivate weeks or years later. While chloroquine can treat the parasites
in red blood cells, hypnozoites need to be cleared to achieve cure. Primaquine has been the mainstay treatment
for elimination of the hypnozoites, but non-adherence jeopardizes cure. Tafenoquine is a long-acting medication that
has recently been approved by the FDA to achieve cure for Plasmodium vivax. Both tafenoquine and primaquine can cause
hemolysis in those with G6PD deficiency. The DETECTIVE trial was a double blind, parallel
group, randomized phase 3 study that assessed the use of tafenoquine in Peru, Brazil, Ethiopia, Thailand, Cambodia, and the Philippines. 522 adults with microscopically confirmed
Plasmodium vivax infection and greater than 70% normal G6PD activity were treated with
a 3-day course of chloroquine and then randomized to a single 300 mg dose of tafenoquine, placebo, or a 15
mg dose of primaquine daily for 14 days. The primary outcome was 6-month recurrence-free
efficacy, defined as microscopicically confirmed clearance of Plasmodium vivax. Tafenoquine had a significantly higher recurrence-free
efficacy rate over 6 months at 62.4% as compared with 27.7% with placebo as did primaquine at
69.6%. With tafenoquine there were asymptomatic,
transient declines in hemoglobin.. The authors conclude that single dose tafenoquine
significantly reduced the risk of Plasmodium vivax recurrence as compared with placebo in
G6PD-normal patients. Full trial results are available at NEJM.org.

3 thoughts on “Radical Cure of P. vivax Malaria

  1. Knowing that primaquine is an effective treatment for malaria elimination, was the placebo group necessary or even ethical? Giving patients placebo when there is an effective treatment option available doesn't seem quite reasonable.

    Curiously, in a planned patient-level meta-analysis of the GATHER and DETECTIVE trials, tafenoquine was not shown to be noninferior to primaquine.

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