Tafenoquine for preventing relapse in people with Plasmodium vivax malaria

Senaka Rajapakse, Chaturaka Rodrigo, Sumadhya Deepika Fernando

Plasmodium vivax malaria is widespread, and the persistent liver stage causes relapse of the disease which contributes to continued P. vivax transmission. Primaquine is currently the only drug that cures the parasite liver stage, but requires 14 days to be effective and can cause haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In addition, there is some evidence of parasite resistance to the drug. Tafenoquine is a new alternative with a longer half-life. To assess the effects of tafenoquine in people with P. vivax infection. We searched the following databases up to 13 April 2015: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; CINAHL; SCOPUS; and LILACS. We also searched the World Health Organization (WHO) International Clinical Trial Registry Platform and the metaRegister of Controlled Trials (mRCT) for ongoing trials using "tafenoquine" and "malaria" as search terms up to 13 April 2015. Randomized controlled trials (RCTs) in people with P. vivax malaria. Adverse effects of tafenoquine are assessed in populations where people with G6PD deficiency have been excluded, and in populations without screening for G6PD deficiency. All review authors independently extracted data and assessed trial quality. Meta-analysis was carried out where appropriate, and estimates given as relative risk with 95% confidence intervals. We assessed the quality of the evidence using the GRADE approach. Three RCTs met our inclusion criteria, with the asexual infection in both the tafenoquine and comparator arm treated with chloroquine, and in all trials G6PD deficiency patients were excluded. Tafenoquine dose comparisonsThree of the included trials compared eight different dosing regimens. Tafenoquine doses of 300 mg and above resulted in fewer relapses than no hypnozoite treatment over six months follow-up in adults (300 mg single dose: RR 0.19, 95% CI 0.08 to 0.41, one trial, 110 participants, moderate quality evidence; 500 to 600 mg single dose: RR 0.14, 95%CI 0.06 to 0.34, two trials, 122 participants, moderate quality evidence; 1800 mg to 3000 mg in divided doses: RR 0.05, 95% CI 0.01 to 0.23, two trials, 63 participants, low quality evidence).In people with normal G6PD status, there may be little or no difference in serious adverse events (three trials, 358 participants, low quality evidence); or any adverse event (one trial, 272 participants, low quality evidence). Tafenoquine versus primaquine Two of the included trials compared four different dosing regimens of tafenoquine against the standard primaquine regimen of 15 mg/day for 14 days. A single tafenoquine dose of 600 mg may be more effective than primaquine in relation to relapses at six months follow-up (RR 0.29, 95% CI 0.10 to 0.84, two trials, 98 participants, low quality evidence)In people with normal G6PD status, there may be little or no difference for serious adverse events (two trials, 323 participants, low quality evidence) or any adverse event (two trials, 323 participants, low quality evidence) between tafenoquine and primaquine. Tafenoquine prevents relapses after clinically and parasitologically confirmed P. vivax malaria. The drug is untested in pregnancy, children and in G6PD-deficient people. The shorter treatment course is an important practical advantage in people who do not have G6PD deficiency, but the longer half-life may have more substantive consequences if given inadvertently to people with G6PD deficiency.