Efficacy of Three Different Regimens of Primaquine for the Prevention of Relapses of Plasmodium vivax Malaria in the Amazon Basin of Peru

Abstract

Abstract. We evaluated the efficacy of three primaquine (PQ) regimes to prevent relapses with Plasmodium vivax through an open-label randomized trial in Loreto, Peru. Vivax monoinfections were treated with chloroquine for 3 days and PQ in three different regimes: 0.5 mg/kg per day for 5 days (150 mg total), 0.5 mg/kg per day for 7 days (210 mg total), or 0.25 mg/kg per day for 14 days (210 mg total). Biweekly fever assessments and bimonthly thick smears were taken for 210 days. Recurrences after 35 days were considered relapses. One hundred eighty cases were enrolled in each group; 90% of cases completed follow-up. There were no group-related differences in age, sex, or parasitemia. Relapse rates were similar in the 7-and 14-day regimes (16/156 = 10.3% and 22/162 = 13.6%, P = 0.361) and higher in the 5-day group (48/169 = 28.4%, P 0.001 and P = 0.001, respectively). The 7-day PQ regimen used in Peru is as efficacious as the recommended 14-day regimen and superior to 5 treatment days.

Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia

“…Moreover, it is highly unlikely that these recurrences were recrudescence by therapeutic failure to CQ since all participants had a negative PCR for malaria on day 28 posttreatment. Results from similar studies in other parts of the world reported a cumulative incidence of recurrence between 0% and 13.5% after treatment with 0.25 mg/kg/day PQ for 14 days and a follow-up time between 180 and 210 days, which is much lower than what was found in this study (38)(39)(40)(41)(42)(43).…”

“…This percentage is higher than that reported in other studies that used the same PQ supervised regimen and similar length of follow-up and genotyping approach for recurrences (microsatellite loci) (37,40). Additionally, 62.1% of recurrences were classified as relapses according to established criteria based on estimation of the P match within each genetic cluster, which could indicate a problem with efficacy of the PQ regimen used.…”

Efficacy of Chloroquine and Primaquine for the Treatment of Uncomplicated Plasmodium vivax Malaria in Cruzeiro do Sul, Brazil

“…18 Our findings show that P. vivax antimalarial regimen in Cruzeiro do Sul is highly efficacious for the acute phase of the infection, but is associated with moderate recurrent infection rates, mostly relapses, compared with a similar study in Peru. 19 In addition, we noted very good tolerance and rapid parasite clearance with the current firstline treatment of uncomplicated P. vivax malaria in Brazil.…”

“…The median total dose of chloroquine was 23.7 mg/kg (range = 15.0-35.7). 19 were lost to follow up, and seven had P. falciparum infection. Figure 2 shows day of recurrent episodes, either by P. vivax or P. falciparum.…”

“…24 Although primaquine remains the only currently available drug for radical cure after P. vivax and Plasmodium ovale infections, different results in relapse prevention with primaquine have been reported. 19,30 WHO recommends daily dose of 0.25 mg/kg/day (infections acquired in temperate regions) or 0.50 mg/kg/day (infections from tropical regions associated with frequent P. vivax relapses) over 14 days in both situations (total dose of 3.5 mg/kg or 7.0 mg/kg) after reports of frequent relapses in Oceania and east Asia. [31][32][33] The concern around frequent relapses has led CDC to change its recommendation and increase the total primaquine dose to 7.0 mg/kg given over 14 days for radical cure of P. vivax infections acquired in all regions of the world.…”