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Guidelines for the treatment of malaria – 2 edition

There is no evidence that treatment courses shorter than 14 days are effective in preventing
relapses (40,57,80,81). Although 5-day courses of primaquine have been deployed as anti-
relapse therapy in some countries in the past, evidence shows that the 14-day course is
superior in efficacy (25,26). Relapse rates and primaquine sensitivity vary geographically.
The reported incidences of relapses range from 11–26; 7% in India (57,82) to 49–51% in
Afghanistan (80). Relapses may occur one to four times after initiation of radical treatment
(81,83). In patients treated with chloroquine, the first relapse is often suppressed by
pharmacologically active concentrations of chloroquine and, therefore, does not manifest
clinically or parasitologically. The first clinically manifested relapse has been reported
any time after day 16 and up to four years following the primary infection (84–86). Host
immunity is also considered to be a major contributor to the therapeutic response against
relapses (87). Risk factors associated with relapses are female sex, higher parasitaemia at
baseline, shorter number of days with symptoms prior to baseline, and a lower dose of
primaquine (84). Other factors should be considered including body weight, natural relapse
rates and local response to primaquine (88).

Hypnozoites of many strains of P. vivax are susceptible to a total dose of 210 mg of
primaquine (28,38,55,78,80,84,89). Infections with the Chesson strain or primaquine-
resistant strains prevalent in southern regions of Oceania and South-East Asia require
a higher dosage of primaquine (22.5 mg or 30 mg per day for 14 days for a total dose of
315 mg or 420 mg) to prevent relapses (57,77,90). Primaquine is contraindicated in patients
with the inherited enzyme deficiency, glucose-6-phosphate dehydrogenase (91,92) (see
Section A9.3.6 on adverse effects and attachment of use of primaquine based on G6PD
deficiency screening).

Although the long 14-day course of primaquine is a clear disadvantage, it has been
shown that poor adherence to unsupervised 14-day primaquine therapy can be overcome
effectively through patient education (93). The lengthy treatment courses and follow-up
periods make the assessment of primaquine efficacy difficult. Thus, the identification
of P. vivax strains that are resistant to chloroquine and/or to primaquine presents major
challenges.

Alternative drugs are much needed for the radical treatment of P. vivax malaria resistant
to chloroquine and/or primaquine. New drugs, tafenoquine and bulaquine, are currently
being evaluated as an alternative to primaquine in the prevention of relapses (94). However,
this too has haemolytic potential in G6PD-deficient individuals.

a9.3.4 treatment of severe and complicated vivax malaria

Prompt and effective management should be the same as for severe and complicated
falciparum malaria (set out in Section 8 of the main document).

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