Timing of malaria infection during pregnancy has characteristic maternal, infant and placental outcomes.

Linda Kalilani-Phiri,Osward M Nyirenda,Mwayi Madanitsa,Patricia Mawindo,Miriam K Laufer,Blair Wylie,Steve Kamiza,Kingsley Makwakwa,Abbey Masonbrink,Terrie E Taylor,Phillip C Thesing,Atis Muehlenbachs,Gladys Membe,David Joseph Diemert

doi:10.1371/journal.pone.0074643

Abstract

We conducted a clinical study of pregnant women in Blantyre, Malawi to determine the effect of the timing of malaria infection during pregnancy on maternal, infant and placental outcomes. Women were enrolled in their first or second trimester of their first or second pregnancy and followed every four weeks until delivery. Three doses of sulfadoxine-pyrimethamine were given for intermittent preventive treatment for malaria, and all episodes of parasitemia were treated according to the national guidelines. Placentas were collected at delivery and examined for malaria parasites and pigment by histology. Pregnant women had 0.6 episodes of malaria per person year of follow up. Almost all episodes of malaria were detected at enrollment and malaria infection during the follow up period was rare. Malaria and anemia at the first antenatal visit were independently associated with an increased risk of placental malaria detected at delivery. When all episodes of malaria were treated with effective antimalarial medication, only peripheral malaria infection at the time of delivery was associated with adverse maternal and infant outcomes. One quarter of the analyzed placentas had evidence of malaria infection. Placental histology was 78% sensitive and 89% specific for peripheral malaria infection during pregnancy. This study suggests that in this setting of high antifolate drug resistance, three doses of sulfadoxine-pyrimethamine maintain some efficacy in suppressing microscopically detectable parasitemia, although placental infection remains frequent. Even in this urban setting, a large proportion of women have malaria infection at the time of their first antenatal care visit. Interventions to control malaria early and aggressive case detection are required to limit the detrimental effects of pregnancy-associated malaria.

Highlights

Pregnancy is a unique period of vulnerability to malaria infection
Studies designed to evaluate new interventions generally enroll pregnant women when they present for their first antenatal care visit, often late in the second or even in the third trimester, do not include active malaria surveillance during the follow up period, and use placental malaria infection as the primary outcome
These studies are based on several assumptions: that interventions which begin at first antenatal visit are likely to impact outcomes, that episodes of peripheral malaria at all stages of pregnancy will lead to placental infection, and that placental malaria infection is associated with adverse outcomes

Summary

Introduction

Pregnancy is a unique period of vulnerability to malaria infection. This increased susceptibility is attributed to the ability of infected erythrocytes to sequester in the developing placenta, causing chronic infection and placental inflammation. Studies designed to evaluate new interventions generally enroll pregnant women when they present for their first antenatal care visit, often late in the second or even in the third trimester, do not include active malaria surveillance during the follow up period, and use placental malaria infection as the primary outcome. These studies are based on several assumptions: that interventions which begin at first antenatal visit are likely to impact outcomes, that episodes of peripheral malaria at all stages of pregnancy will lead to placental infection, and that placental malaria infection is associated with adverse outcomes

Methods

Results

Conclusion