Impact of Microscopic and Submicroscopic Parasitemia During Pregnancy on Placental Malaria in a High-Transmission Setting in Uganda

Abstract

Background: Placental malaria is a major cause of adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of parasitemia during pregnancy and placental malaria.

Methods: Data came from 637 women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy (IPTp) from Uganda. Plasmodium falciparum parasitemia was assessed using microscopy and ultrasensitive quantitative PCR at intervals of 28 days from 12 to 20 weeks gestation through delivery. Multivariate analysis was used to measure associations between characteristics of parasitemia during pregnancy and the risk of placental malaria based on histopathology.

Results: Overall risk of placental malaria was 44.6%. None of the 34 women without parasitemia detected during pregnancy had evidence of placental malaria. Increasing proportion of interval assessments with parasitemia and higher parasite densities were independently associated with an increased risk of placental malaria. Higher gravidity and more effective IPTp were associated with a decreased risk of placental malaria. Women with parasitemia only detected before the third trimester still had an increased risk of placental malaria.

Conclusions: The frequency, density, and timing of parasitemia are all important risk factors for placental malaria. Interventions should target the prevention of all levels of parasitemia throughout pregnancy.

Keywords: asymptomatic malaria infection; dihydroartemisinin-piperaquine; intermittent preventive treatment during pregnancy; microscopic parasitemia; placental malaria; submicroscopic parasitemia.

Figure 1.

Flowchart of study participants. Abbreviations: DP, dihydroartemisinin-piperaquine; HIV, human immunodeficiency virus; SP, sulfadoxine-pyrimethamine.

Figure 2.

Proportion of women with placental malaria by (A) proportion of interval assessments with microscopic parasitemia and (B) proportion of interval assessments with any parasitemia. Numbers at the bottom of each bar represent the total number of patients in the category (n). Error bars represent 95% confidence intervals of the proportions.

Figure 3.

Proportion of high-powered microscopy fields with pigment by proportion of interval assessments with any parasitemia among those with placental malaria. Numbers at the bottom of each bar represent the total number of patients in the category (n). Boxes represent interquartile range (IQR), with median represented as a horizontal band. Whiskers extend to Q3 + 1.5IQR and Q1 − 1.5IQR.

Figure 4.

Proportion of women with placental malaria by geometric mean parasite density, stratified by proportion of interval assessments with any parasitemia. Numbers at the bottom of each bar represent the total number of patients in the category (n). Error bars represent 95% confidence intervals of the proportions.