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Guidelines for the treatment of malaria – 2 edition

a9.4 monitoring therapeutic efficacy
There is a need to monitor the antimalarial sensitivity of P. vivax in order to improve the
treatment of vivax malaria, in particular in view of its emerging resistance to chloroquine.
An in vitro test system has been developed for assessing the parasite’s sensitivity to
antimalarials (95,96). A modified version of the standard WHO in vitro micro-test for
determination of the antimalarial sensitivity of P. falciparum has been used successfully for
assessing the antimalarial sensitivity of P. vivax populations and for screening the efficacy
of new antimalarials by measuring minimal inhibitory concentration (MIC), and the
concentrations providing 50% and 90% inhibition (IC50), and (IC90) (89, 97). WHO has
also recently introduced a revised protocol for in vivo monitoring of the therapeutic efficacy
of chloroquine in P. vivax malaria (98). The revised protocol includes measurement of blood
chloroquine levels, PCR genotyping and the use of molecular markers (only available for
the dhfr gene) to help clarify and complete the overall picture of drug resistance. A better
understanding of the molecular mechanisms underlying drug resistance in P. vivax is
needed to improve the monitoring of chloroquine resistance.

a9.5 conclusions and recommendations

The standard oral regimen of chloroquine of 25 mg base/kg body weight given over 3 days
plus primaquine at either a low (0.25 mg base/kg body weight per day for 14 days) or high
(0.5–0.75 mg base/kg body weight per day for 14 days) dose is effective and safe for the radical
cure of chloroquine-sensitive P. vivax malaria in patients with no G6PD deficiency.
In areas where infections of drug-resistant P. falciparum and/or P. vivax are common, drug
regimens to treat both species effectively must be used. An artemisinin-based combination
treatment (particularly dihydroartemisinin plus piperaquine) that does not include
sulfadoxine-pyrimethamine would be a good choice.

The use of high-dose primaquine (0.5–0.75 mg base/kg body weight per day for 14 days),
with either chloroquine or another effective antimalarial, is essential for trying to prevent
relapses of primaquine-resistant or primaquine-tolerant P. vivax.
A primaquine regimen of 0.75 mg base/kg body weight once per week for 8 weeks is
recommended as anti-relapse therapy for P. vivax and P. ovale malaria in patients with
mild G6PD deficiency.
Increased efforts are needed to evaluate alternative treatments for P. vivax strains that
are resistant to chloroquine. Urgent needs include establishing in vitro culture of P. vivax
to permit the assessment of drug susceptibility, research to improve understanding of
the molecular mechanisms of drug resistance, and the development of better tools for
genotyping P. vivax.
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