Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial.
BACKGROUND
The widespread increase in resistance of Plasmodium falciparum to chloroquine and sulphadoxine-pyrimethamine threatens the use of these drugs for malaria treatment in pregnancy. We aimed to assess the safety and efficacy of amodiaquine alone or in combination with sulphadoxine-pyrimethamine as alternative regimens.


METHODS
Pregnant women with a gestational age of 16 weeks or more who attended antenatal clinics at a district hospital in Ghana were screened for malaria with OptiMAL dipsticks. 900 pregnant women who had a positive test result and P falciparum asexual stage parasitaemia were enrolled and randomly assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, or amodiaquine plus sulphadoxine-pyrimethamine. The primary outcome was parasitological failure by day 28 of treatment. Women were seen on days 3, 7, 14, and 28 after the start of treatment to assess the effect of treatment on peripheral parasitaemia, haemoglobin concentration, white-blood-cell count, and liver function. Additionally, reports of adverse effects were solicited and monitored during follow-up visits. Analysis was by intention to treat. This trial is registered with the US National Institute of Health clinical trials database number NCT00131703.


RESULTS
PCR-corrected parasitological failure by day 28 was 14%, 11%, 3%, and 0% in the women assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, and amodiaquine plus sulphadoxine-pyrimethamine, respectively (p<0.0001). No serious liver toxic effects or white-blood-cell dyscrasias were noted. Minor side-effects were reported more often on day 3 by women receiving amodiaquine (86%) or amodiaquine plus sulphadoxine-pyrimethamine (90%) than those receiving sulphadoxine-pyrimethamine (48%) or no antimalarial drugs (34%; p<0.0001 for every comparison).


CONCLUSIONS
Amodiaquine alone or in combination with sulphadoxine-pyrimethamine, although associated with minor side-effects, is effective when used to treat malaria in pregnancy.
Tagbor
Harry
H
St Theresa's Hospital, Nkoranza, Ghana. Harry.Tagbor@lshtm.ac.uk
Bruce
Jane
J
Browne
Edmund
E
Randal
Anna
A
Greenwood
Brian
B
Chandramohan
Daniel
D
D000328:Adult; D000655:Amodiaquine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002738:Chloroquine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005869:Ghana; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy*; D011739:Pyrimethamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine