Two-dose versus monthly intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine in HIV-positive pregnant women

Malaria during pregnancy carries risks of maternal mortality and anaemia and foetal mortality, growth retardation, preterm birth and low birth rate. HIV-positive pregnant women have greater risk of malarial parasitemia, higher parasite densities, higher anaemia rates and more frequent placental infections and birth complications than HIV-negative women.

Intermittent preventive treatment of malaria during pregnancy (IPTp) reduces these risks, but the optimal dosing regimen for HIV-positive women in unclear.

A paper authored by Davidson Hamer and coworkers published in the December 1 edition of The Journal of Infectious Diseases reported findings from a randomised, double-blind, placebo-controlled study conducted in Zambia between January 2003 and October 2004, to compare the standard 2-dose sulfadoxine-pyrimethamine (SP) regimen with monthly IPTp. [1]

In this study mothers were randomised to dosing schedules of either one, treatment course of sulfadoxine-pyrimethamine per month, intensive regimen (I-IPTp) or per trimester, standard regimen (S-IPTp), (2-dose).

456 HIV-positive women enrolled in the study, 224 were randomised to the I-IPT-p arm and 232 to the S-IPTp arm. Loss to follow up was 16.1% for I-IPTp vs. 13.8% for S-IPTp group.

Women in the I-IPTp group received a median of 4 doses, with 1% receiving only 1 dose, 5% receiving 2 doses, 29% receiving 3 doses, 36% receiving 4 doses, and 29% receiving 5 or more doses. Of the S-IPTp group, 84% received 2 courses of SP, and the remaining women only 1 treatment course.

The investigators found no differences between I-IPTp and standard S-IPTp in placental malaria by histopathology (26% vs. 29%; relative risk [RR], 0.90 [95% confidence CI, 0.641.26]) or placental parasitemia (2% vs. 4%; RR, 0.55 [95% CI, 0.171.79]). There also were no differences in maternal anaemia, stillbirths, preterm delivery, low birth weight, or infant mortality at 6 weeks.

The investigators concluded that this study produced no convincing evidence that the I-IPT was superior to S-IPT in an area of relatively mild malaria transmission. However they cited an accompanying article authored by Gill et al from the same group which described their finding that single dose SP , a common result of trying to implement the standard 2-dose regimen was significantly associated with higher proportions of maternal anaemia, peripheral and cord blood parasitemia, infant prematurity, and low birth weight. [2]

This study revealed dose-dependent benefits, particularly in the transition from 1 to 2 doses of SP.

The investigators suggest that at a programmatic level, for HIV-positive women, monthly SP IPTp may ultimately be more effective than the standard regimen by reducing the risk of inadvertently underdosing mothers.