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Guidelines for the treatment of malaria – 2 edition

box 9.1
recommendation: ACTs for treatment of chloroquine resistant uncomplicated P. vivax malaria

 in areas with chloroquine resistant P. vivax, artemisinin-based combination therapies (particularly
with those whose partner medicines have long-half lives) are recommended for the treatment
of P. vivax malaria. Weak recommendation, moderate quality evidence
GraDE evaluation (see Annex 9, tables A9.6.1 and A9.6.2)
Two trials compared DHA+PPQ to alternative ACTs (AL6 and AS+AQ) in Indonesia where all groups were
also given primaquine to clear the liver stage parasites. DHA+PPQ reduced the number of relapses by
day 42 compared to AL (1 trial, 126 participants; RR 0.16, 95% CI 0.07–0.38; moderate quality evidence)
and AS+AQ (1 trial, 84 participants; RR 0.16, 95% CI 0.05–0.49; moderate quality evidence). There are no
trials comparing DHA+PPQ and AS+MQ in P. vivax mono-infection.
At day 42, the patients in the DHA+PPQ groups were also less likely to be anaemic, although this data includes
participants with P. falciparum mono-infection at baseline, and recurrence of P. falciparum was also lower with
DHA+PPQ. This effect is likely to be a prophylactic effect related to the longer half-life of DHA+PPQ.

Other considerations
The panel noted the programmatic advantage of these ACTs also being highly effective against P. falciparum.
This effect is likely to be a prophylactic effect related to the longer half-life of DHA+PPQ.

9.3.2 Liver stage infection
To achieve a radical cure, relapses must be prevented by giving primaquine. The frequency
and pattern of relapses varies geographically. Whereas 50–60% of P. vivax infections
in South-East Asia relapse, the frequency is lower in Indonesia (30%) and the Indian
subcontinent (15–20%). Some P. vivax infections in the Korean peninsula (now the most
northerly of human malarias) have an incubation period of nearly one year. Moreover, the
P. vivax populations emerging from hypnozoites commonly differ from the populations
that caused the acute episode. Activation of heterologous hypnozoites populations is
the most common cause of the first relapse in patients with vivax malaria. Thus, the
preventive efficacy of primaquine must be set against the prevalent relapse frequency. It
appears that the total dose of 8-aminoquinoline given is the main determinant of curative
efficacy against liver-stage infection. In comparison with no primaquine treatment,
the risk of relapse decreased by the additional milligram per kilogram body weight of
primaquine given. Primaquine should be given for 14 days.
A Cochrane Review reports both direct and indirect comparison of a 14-day versus 5-day
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regimen of primaquine. The review reports indirect evidence of the superiority of the
14-day regimen. No difference has been shown between the 5-day regimen and chloroquine
alone (3 trials, 2104 participants; odds ratio [OR] 1.04, 95% CI 0.64–1.69), while the

14 Galappaththy GNL, Omari AAA, Tharyan P. Primaquine for preventing relapses in people with Plasmodium vivax
malaria. Cochrane Database of Systematic Reviews, 2007, Issue 1 (Article No. CD004389). doi: 10.1002/14651858.
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