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7. Treatment of uncomplicated P. falciparum malaria

that the artemisinin derivatives should be used to treat uncomplicated falciparum malaria
in the second and third trimesters of pregnancy. The choice of combination partner is
difficult because of limited information. Mefloquine monotherapy has been associated
with an increased risk of stillbirth in large studies in Thailand, but not in Malawi. The
current standard six-dose artemether plus lumefantrine regimen has been evaluated in
125 women in the second and third trimesters in a controlled trial for the treatment of
uncomplicated falciparum malaria on the Burmese-Thai border. It was well tolerated
and safe, but efficacy was inferior to seven days of artesunate monotherapy. Reduced
efficacy probably resulted from low drug concentrations in later pregnancy. Although
many pregnant women in Africa have been exposed to artemether plus lumefantrine in
the second and third trimesters of pregnancy, formal studies to evaluate its efficacy and
safety in pregnant women in Africa are still ongoing. Similarly, many pregnant women
in Africa have been treated with amodiaquine alone or combined with SP or artesunate;
however the use of amodiaquine in pregnancy has only been documented in just over
500 pregnancies (with safety assessments in 450 of them). Amodiaquine use in Ghanaian
pregnant women in the second and third trimesters was associated with frequent minor
side effects, but it was not associated with liver toxicity or bone marrow depression or
adverse neonatal outcome. There is no published information about the combination of
amodiaquine and artesunate.
On the Burmese-Thai border, DHA+PPQ has been used successfully in the second and
third trimesters of pregnancy in 50 women for rescue therapy and for treatment in 104
pregnant women in West Papua province (Indonesia). Sulfadoxine-pyrimethamine,
though considered safe, is compromised for treatment in many areas because of increasing
resistance. If AS+SP is used for treatment, the co-administration of high dose (5 mg)
daily folate supplementation should be avoided as this compromises the efficacy of SP
in pregnancy. Lower folate dosing (0.4–0.5 mg/day) should be used in women receiving
AS+SP for the treatment of malaria, or treatments other than SP should be used.
Clindamycin is also considered safe, but it must be given for seven days in combination
with quinine. Quinine is associated with an increased risk of hypoglycaemia in late
pregnancy, and it should be used only if effective alternatives are not available. Primaquine
and tetracyclines should not be used in pregnancy.

box 7.5
recommendations: treatment of uncomplicated falciparum malaria in pregnancy

 first trimester:
• Quinine plus clindamycin to be given for 7 days (artesunate plus clindamycin for 7 days is indicated if this
a
treatment fails).
• An ACT is indicated only if this is the only treatment immediately available, or if treatment with 7-day
quinine plus clindamycin fails, or if there is uncertainty about patient compliance with a 7-day treatment.

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