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Guidelines for the treatment of malaria – 2 edition

courses of primaquine have been deployed in the past, evidence indicates that a 14-day
regimen is superior in preventing relapses (25, 26). The optimal dose of primaquine differs
in geographical areas, depending on the relapsing nature of the infecting strain, and it
remains unclear in patients of heavy body weight (27). This combination of chloroquine
and primaquine constitutes treatment to achieve radical cure of vivax malaria.

Primaquine also has weak activity against blood stage parasites. The radical cure regimen
of vivax malaria with chloroquine and primaquine, therefore, conforms to the definition
of a combination therapy. The combination of any antimalarial against P. vivax infections
with primaquine has improved cure rates (22–24, 28, 29), and it is, therefore, useful in the
treatment of chloroquine-resistant P. vivax infections.

a9.3.2 treatment of chloroquine-resistant P. vivax

Therapeutic efficacy data available to date indicate that P. vivax remains sensitive to
chloroquine throughout most of the world (22,30–44) with the exception of Indonesia
where high therapeutic failure rates ranging from 5–84% have been reported on day 28
of follow-up (22,29,45–50). There are reports of chloroquine failure as both treatment
and prophylaxis against P. vivax malaria from several other countries and regions where
the species is endemic (51–54). Some of these studies did not measure chloroquine drug
concentrations, so that it is questionable whether these findings represented strictly defined
chloroquine resistance (35,39,40,42,44,55–58).

Antimalarials that are effective against P. falciparum are generally effective against the
other human malarias. The exception to this is sulfadoxine-pyrimethamine to which
P. vivax is commonly resistant. Owing to the high prevalence of dhfr mutations in P. vivax
(Pvdhfr), resistance to sulfadoxine-pyrimethamine develops faster in this parasite than in
P. falciparum, and resistant P. vivax become prevalent in areas where this drug is used for
the treatment of falciparum malaria (38,59–67).
Artemisinins, when combined with an effective partner medicine, have provided excellent
cure rates in both chloroquine sensitive and chloroquine resistant strains of P. vivax, as
recent following evidence indicates: AL produces comparable cure rates to CQ in the
treatment of P. vivax which is sensitive to CQ (68,69). In areas of CQ resistance, two ACTs,
DHA+PPQ (70, 71) and AS+AQ (70), in combination with primaquine, have provided high
cure rates. ACTs with partner medicines that have longer half-lives, such as DHA+PPQ, are
more effective in reducing relapses than those with shorter half-lives (70, 71).

Other monotherapies that have been tested for the treatment of P. vivax malaria with
varying degrees of efficacy including amodiaquine (25–30 mg base/kg body weight given
over 3 days), which has been used effectively for the treatment of chloroquine-resistant
vivax malaria (72) and has been well tolerated (73–75). The risk of relapse of P. vivax malaria
without primaquine therapy ranged from 5–80% or more, depending largely upon the
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