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ANNEX 9. Treatment of Plasmodium vivax, P. ovale and P. malariae infections

geographic location and, therefore, primaquine must be added for radical cure. Mild nausea,
vomiting and abdominal pain are the commonly reported adverse reactions (75).

• Mefloquine (15 mg base/kg body weight as a single dose) has been found to be highly
effective with a treatment success of 100% (38).
• Doxycycline alone (100 mg twice a day for 7 days) provides poor cure rates in P. vivax
(47).

• Artemisinin derivatives, such as monotherapy for 3–7 days, have shown poor efficacy in
vivax malaria with day 28 cure rates of 47–77% (23,38,56). The addition of primaquine
to these regimes improved the day 28 cure rates to 100% (23,76).

• Quinine (10 mg salt/kg body weight three times a day for 7 days) (72) is also effective
against CQ resistant P. vivax, but it is not an ideal treatment because of its toxicity
and consequent poor adherence to this regimen. A study in Thailand has found that
treatment of vivax malaria with quinine leads to early relapses. This may be because
quinine has a short half-life, and no antihypnozoite activity (38).
The best combinations for the treatment of P. vivax are those containing primaquine when
given in antihypnozoite doses (28,30,38,40,57,75,77,78).
The recommended treatments for CQ resistant P. vivax are, therefore, ACTs (with the
exception of AS+SP) combined with primaquine at antihypnozoite doses (see below).
Unlike P. falciparum, P. vivax cannot be cultured continuously in vitro: so it is more difficult
to determine the in vitro sensitivity of P. vivax to antimalarials. In vivo assessment of the
therapeutic efficacy of drugs against P. vivax malaria is also compounded by difficulties in
distinguishing recrudescences due to drug-resistant infections from relapses. The interval
between the primary and repeat infection can serve as a general guide. If the recurrence
appears within 16 days of starting treatment of the primary infection, it is almost certainly
a recrudescence due to therapeutic failure. A recurrence between days 17 and 28 may be
either a recrudescence by chloroquine-resistant parasites or a relapse. Beyond day 28, any
recurrence probably represents a relapse in an infection of chloroquine-sensitive P. vivax
(79). A recurrent vivax parasitaemia in the presence of chloroquine blood levels exceeding
100 ng/ml, and a parasite genotype identical with the primary infection as detected by
polymerase chain reaction, are more suggestive of chloroquine resistance to the primary
infection than a relapse infection. A9

a9.3.3 preventive therapy for relapses

Primaquine is the only available and marketed drug that can eliminate the latent hypnozoite
reservoirs of P. vivax and P. ovale that cause relapses. P. vivax populations emerging from
hypnozoites commonly differ from the populations that caused the acute episode (69).
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