Tafenoquine for preventing relapse in people with Plasmodium vivax malaria

06 Sep 2020

What was the aim of this review?

The aim of this review was to see if tafenoquine could prevent relapses of vivax infections and if this effect is equivalent to that of standard‐dose primaquine. Standard‐dose primaquine is defined as 15 mg/day for 14 days for adults.

Key messages

Tafenoquine prevents vivax malaria relapses (measured as recurrences of infection in all studies as it is not possible to differentiate a true relapse from a reinfection) in adults compared to no relapse prevention treatment (placebo). There is also probably little or no difference between tafenoquine and primaquine in preventing relapses. The evidence was of moderate certainty due to the low number of studies and few data. There is probably little or no difference in the overall adverse events with tafenoquine compared to placebo or primaquine. However, we are uncertain if tafenoquine causes more serious adverse events such as a drop in blood haemoglobin.

What was studied in this review?

Vivax malaria is caused by the parasite Plasmodium vivax. The disease includes a dormant (inactive) stage of liver infection and this can cause relapse (worsening) unless it is treated.

The most frequently used medicine for relapse prevention until recently was primaquine, but now there is a new alternative named tafenoquine. The US agency responsible for protecting public health, the Food and Drug Administration (FDA), recommends tafenoquine for relapse prevention at a single 300 mg dose. Compared to primaquine, which is usually given daily for 14 days, single‐day dosing provides a significant advantage. However, both primaquine and tafenoquine can cause rupture or destruction of red blood cells (called haemolysis) in people with a hereditary condition called glucose‐6‐phosphate dehydrogenase (G6PD) enzyme deficiency.

We conducted a Cochrane Review on the effect of tafenoquine on clearing the dormant P vivax parasites in infected people to prevent a relapse. However, it is difficult to differentiate between a true relapse and a new infection in the same individual unless the person was removed from a malaria‐endemic area after initial treatment. All trials included in this review did not do that and have actually measured recurrences as a proxy measure to infer on relapses. While acknowledging this limitation, in giving recommendations and results in this review we used the word 'relapse' as preventing relapses is the intention for using tafenoquine as a single dose in these trials.

What are the main results of the review?

We examined the research published up to 3 June 2020. We identified three trials conducted in nine countries in 747 adults with confirmed P vivax malaria. All adults received chloroquine (to clear the parasites from the blood) and some groups received either tafenoquine in a single dose of 300 mg, primaquine or placebo (an inactive tablet matched for the duration of primaquine). All were observed for recurrences of P vivax malaria (up to six months) and all trials tested people for G6PD activity and excluded people who were deficient. Pregnant women and children were also excluded.

Adults receiving tafenoquine 300 mg had fewer relapses (inferred from the lower number of recurrences of infection) than adults who had placebo (moderate‐certainty evidence). There was probably little or no difference between Tafenoquine 300 mg and primaquine for relapse prevention (moderate‐certainty evidence). There is probably little or no difference in overall side effects between tafenoquine and primaquine (moderate‐certainty evidence). We are uncertain though if tafenoquine causes more serious adverse events compared to placebo or premaquine (for example, haemolysis; very low‐certainty evidence).