Divala TH, et al. - In southern Africa, as chloroquine efficacy has returned, researchers investigate whether chloroquine, either as an intermittent therapy or as weekly chemoprophylaxis, is more efficacious than intermittent sulfadoxine-pyrimethamine for prevention of malaria in pregnancy and related maternal and newborn adverse outcomes. In a setting of high resistance to sulfadoxine-pyrimethamine, chloroquine administered as intermittent therapy resulted in no better protection from malaria and related adverse effects vs intermittent sulfadoxine-pyrimethamine. Findings suggest a possible efficacy of chloroquine chemoprophylaxis in providing benefit in protecting against malaria during pregnancy.

Methods

• At Ndirande Health Centre, Blantyre, in southern Malawi, an open-label, single-center, randomized controlled trial was performed.
• Pregnant women (first or second pregnancy) at 20–28 weeks' gestation who were HIV negative were enrolled.
• Random assignment of participants in a 1:1:1 ratio was performed using a computer-generated list to either intermittent sulfadoxine-pyrimethamine (two doses of 1,500 mg sulfadoxine and 75 mg pyrimethamine, 4 weeks apart), intermittent chloroquine (two doses of 600 mg on day 1, 600 mg on day 2, and 300 mg on day 3), or chloroquine prophylaxis (600 mg on day 1 then 300 mg every week).
• Placental malaria in the modified intent-to-treat population was the primary endpoint; this population was comprised of participants who contributed placental histopathology data at birth.
• Clinical malaria, maternal anemia, low birthweight, and safety were the secondary outcomes.

Results

• Nine hundred women were enrolled and randomly allocated between February 2012 and May 2014; of these, 765 contributed histopathological data and were included in the primary analysis.
• Placental malaria was recorded for 108 (14%) women, which was lower than the anticipated prevalence of placental malaria infection.
• No improvement in protection from placental malaria was noted using chloroquine as either prophylaxis (30 [12%] of 259 had positive histopathology; relative risk [RR] 0.75, 95% CI 0.48–1.17) or intermittent therapy (39 [15%] of 253; RR 1.00, 0.67–1.50) compared with intermittent sulfadoxine-pyrimethamine (39 [15%] of 253).
• In protocol-specified analyses adjusted for maternal age, gestational age at enrolment, bednet use the night before enrolment, anemia at enrolment, and malaria infection at enrolment, 34% lower placental infections was observed among women taking chloroquine as prophylaxis compared to those allocated intermittent sulfadoxine-pyrimethamine (RR 0.66, 95% CI 0.46–0.95).
• Researchers reported clinical malaria in nine women assigned intermittent sulfadoxine-pyrimethamine, four allocated intermittent chloroquine (p=0.26), and two allocated chloroquine prophylaxis (p=0.063).
• Five women assigned intermittent sulfadoxine-pyrimethamine, 15 allocated intermittent chloroquine (p=0.038), and six assigned chloroquine prophylaxis (p > 0.99) had anemia.
• Thirty-one babies born to women allocated intermittent sulfadoxine-pyrimethamine, 29 assigned intermittent chloroquine (p=0.78), and 41 allocated chloroquine prophylaxis (p=0.28) had low birthweight.
• Adverse events were encountered in four women assigned intermittent sulfadoxine-pyrimethamine, which were possibly related to study product vs 94 women allocated intermittent chloroquine (p < 0.0001) and 26 allocated chloroquine prophylaxis (p < 0.0001).
• Severe or life-threatening adverse events related to study product were encountered in three women, all of these were assigned intermittent chloroquine (p=0.25).