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

a9.3.5 treatment of malaria caused by P. ovale and P. malariae
Resistance of P. ovale and P. malariae to antimalarials is not well characterized, and these
infections are considered to be generally sensitive to chloroquine. Only a single study in
Indonesia has reported P. malariae resistance to chloroquine (64). The recommended
treatment for radical cure of P. ovale, relapsing malaria, is the same as that for P. vivax,
i.e. with chloroquine and primaquine. The high prevalence of G6PD deficiency status in
areas endemic for P. ovale calls for the same caution in the use of primaquine as stated in
Section A9.3.6, P. malariae forms no hypnozoites, and so it does not require radical cure
with primaquine.

a9.3.6 adverse effects and contraindications

Chloroquine is generally well tolerated. Common side effects include mild dizziness,
nausea, vomiting, abdominal pain and itching (4,72,87).
Primaquine can induce a life-threatening haemolysis in those who are deficient in the
enzyme G6PD (see Section A9.3.3). The severity of hemolytic anaemia seems to be related
to primaquine dosing and the variant of the G6PD enzyme (108). Methemoglobinemia
is associated with G6PD deficiency in malaria patients treated with primaquine (109).
A full course of primaquine, given as a daily dose of 0.25 mg base/kg body weight for
14 days, is reported to be safe in populations where G6PD deficiency is either absent or
readily diagnosable, but could induce a self-limiting haemolysis in those with mild G6PD
deficiency (35,55,57). To reduce the risk of haemolysis in such individuals, an intermittent
primaquine regimen of 0.75 mg base/kg weekly for 8 weeks can be given under medical
supervision. This regimen is safe and effective (92). In non-G6PD deficient individuals, a
high dose of primaquine (30 mg/day) has been shown to be safe and effective for Chesson
strain P. vivax malaria in South-East Asia during a 28-day follow-up (23,77,90). In
regions where prevalence of G6PD deficiency is relatively high, G6PD testing is required
before administration of primaquine (see Fig. A9.1). Primaquine is not recommended
during pregnancy and in infancy, since limited safety data are available in these groups
(79). Abdominal pain and/or cramps are commonly reported when primaquine is taken
on an empty stomach. Gastrointestinal toxicity is dose-related, and it is improved by
taking primaquine with food. Primaquine may cause weakness, uneasiness in the chest,
haemolytic anaemia, methaemoglobinaemia (which occurs in non-haemolysed red cells), A9
leukopenia, and suppression of myeloid series. Therefore, primaquine should not be given
in conditions predisposing to granulocytopenia, which includes rheumatoid arthritis and
lupus erythematosus.

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