Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine
Malaria due to Plasmodium vivax parasites is widespread. The World Health Organization (WHO) recommends that people with P. vivax malaria are treated with chloroquine for three days to eliminate the parasites in the blood that cause the symptoms of malaria, followed by 15 mg/day of primaquine for 14 days to treat the liver stage of the infection to prevent the disease recurring. However, many people do not complete the primaquine treatment once they feel better after chloroquine treatment. In addition, primaquine can destroy red blood cells in people with a genetic enzyme deficiency (glucose-6-phosphate-dehydrogenase enzyme (G6PD) deficiency), and clinicians avoid giving primaquine in areas where people commonly have this deficiency. Shorter courses of primaquine could potentially increase treatment completion and reduce adverse events.
The review authors included 15 trials of 4377 adults and children older than one year with vivax malaria. All were treated with chloroquine for the blood stage infection, and then randomized to the 14-day primaquine course, or to shorter primaquine courses (three, five, or seven days); or to higher doses of primaquine given once a week for eight weeks; or to a placebo or no treatment. In twelve studies, treatments were supervised. The evidence is current to 8 October 2013.
Relapse over six months to one year is probably higher with shorter regimens when compared to the standard 14-day primaquine regimen (moderate quality evidence). We do not know from the available evidence whether the number of relapses with weekly primaquine differs from 14 days of primaquine treatment based on one study of 126 people followed up for nine months (very low quality evidence). Better conducted studies on more people are needed to be sure that they are equally effective against relapse. Five days of primaquine was as ineffective against relapse as placebo or no treatment over six months to 15 months based on four studies (high quality evidence). The 14-day primaquine course prevented many more people relapsing with vivax malaria over 12 months than placebo (high quality evidence). No serious adverse reactions to primaquine were reported.
This review update confirms that the 14-day primaquine course recommended by the WHO is more effective against relapse of vivax malaria than treatment with shorter courses of primaquine.
Galappaththy, G.N.L.; Tharyan, P.; Kirubakaran, R. Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine. Cochrane Database of Systematic Reviews (2013) Issue 10, Art. No.: CD004389. [DOI: 10.1002/14651858.CD004389.pub3]