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Comparable efficacy of chloroquine, sulfadoxine-pyrimethamine against malaria in pregnancy

Tristan Manalac
14 Sep 2018
Infographic: Unravelling the 4,000 year history of malaria

Intermittent chloroquine therapy is not superior to sulfadoxine-pyrimethamine in protecting pregnant mothers against malaria and related adverse events, according to a recent study.

“The role of chloroquine as a potential replacement for sulfadoxine-pyrimethamine for the prevention of malaria during pregnancy remains to be established fully. However, as the search for alternative regimens continues, chloroquine prophylaxis needs to remain an important consideration for future trials, perhaps in higher transmission settings,” said researchers.

Researchers randomly assigned 900 HIV-negative pregnant women to receive intermittent sulfadoxine-pyrimethamine (m=300; mean age 20.4±3.1 years), intermittent chloroquine (n=300; mean age 20.7±3.2 years) or chloroquine prophylaxis (n=300; mean age 20.4±3.6 years). Placental malaria was detected in 14 percent (n=108) of the women. [Lancet Infect Dis 2018;doi:10.1016/S1473-3099(18)30415-8]

Stratifying the findings according to treatment revealed that the prevalence of a positive histopathology for placental malaria was consistently low across all three groups (chloroquine prophylaxis: 12 percent; intermittent chloroquine: 15 percent; intermittent sulfadoxine-pyrimethamine: 15 percent).

In terms of efficacy, both intermittent chloroquine and sulfadoxine-pyrimethamine treatments resulted in statistically comparable likelihoods of testing positive for placental malaria using histopathology (relative risk [RR], 0.99; 95 percent CI, 0.69–1.41; p=0.94). In comparison, chloroquine prophylaxis was superior to intermittent sulfadoxine-pyrimethamine (RR, 0.66; 0.46–0.95; p=0.027).

These findings were confirmed in multivariable models, which showed that intermittent chloroquine had no significant impact on the risk of placental malaria both in patients with (estimate, 0.97; 0.69–1.35; p=0.84) and without (estimate, 1.00; 0.59–1.67; p=0.99) baseline malaria.

On the other hand, chloroquine prophylaxis was significantly protective in patients without baseline malaria (estimate, 0.44; 0.23–0.85; p=0.014).

Similar trends were observed for prenatal and perinatal outcomes. Maternal anaemia was reported in 19 percent (n=168) of the participants, 20 percent each in both intermittent preventive treatment groups and 16 percent in the chloroquine prophylaxis group. Intermittent chloroquine and sulfadoxine-pyrimethamine led to comparable risks of maternal anaemia (RR, 1.02; 0.74–1.40; p>0.99).

The same was true for prenatal severe maternal anaemia (RR, 1.00; 0.11–9.55; p>0.99) and infant outcomes such as low birthweight (RR, 0.91; 0.57–1.45; p=0.78), preterm delivery (RR, 1.50; 0.86–2.63; p=0.17) and infant death (RR, 1.20; 0.50–2.92; p=0.81).

However, maternal anaemia at delivery was significantly more common in the intermittent chloroquine vs sulfadoxine-pyrimethamine group (5 percent vs 2 percent; RR, 3.00; 1.15–7.87; p=0.038).

“[O]ur study did not show superiority of chloroquine over intermittent preventive treatment with sulfadoxine-pyrimethamine for prevention of malaria during pregnancy and associated maternal and infant adverse outcomes,” researchers said, noting that a low event rate could largely be responsible for this.

“However, the results of our adjusted analysis and intention-to-treat safety analyses suggest that chloroquine prophylaxis remains a valuable alternative to sulfadoxine-pyrimethamine,” they said, particularly in eastern and parts of western Africa, where chloroquine-susceptible malaria is common.

In an accompanying commentary, R Matthew Chico of the London School of Hygiene and Tropical Medicine and Feiko Oter Kuile of the Liverpool School of Tropical Medicine agreed: “Evidence from the [present trial] is unlikely to swing the pendulum back in favour of chloroquine prophylaxis.” [Lancet Infect Dis 2018;doi:10.1016/S1473-3099(18)30427-4]

“Nevertheless, with the return of chloroquine susceptibility in many parts of Africa, use of chloroquine in the first trimester might be worth investigating further… If we can learn anything from this study and other trials, it is to temper our expectations,” they added.

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