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About the Authors:
Whitney E. Harrington
Affiliation: Seattle Children's Hospital/University of Washington School of Medicine, Department of Pediatrics, Seattle, Washington, United States of America
Robert Morrison
Affiliation: Seattle Biomedical Research Institute, Seattle, Washington, United States of America
Michal Fried
Affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America
Patrick E. Duffy
* E-mail: [email protected]
Affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America
Introduction
Malaria in pregnancy is associated with numerous poor outcomes including maternal anemia [1], [2] and hypertension [3], stillbirth, premature delivery, intra-uterine growth retardation [2], low birth weight [1], [2], and perinatal death [4]. In addition to poor delivery outcomes, placental malaria (PM) is also associated with increased susceptibility to parasitemia [5], [6] and clinical malaria during infancy [5], [7] with regard to both time to first event and overall risk. Evidence suggests that this effect may be most prominent among offspring of multigravid women [6], [7]. A conclusive explanation has yet to be determined but may involve alterations in maternally transmitted malaria-specific antibodies [5] or prenatal immune priming against malaria antigens [8], [9], [10], [11].
Intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) is used to prevent many of the harmful consequences of malaria in pregnancy, an approach that has been successful in areas of low resistance [12]. However, in an area of widespread resistance we recently observed that IPTp did not reduce the odds of PM and failed to improve other delivery outcomes [13]. In addition, among PM+ women in this population, IPTp was associated with increased drug resistance alleles, placental parasite density, and inflammation [14]. These findings are consistent with parasite competitive facilitation, a phenomenon where drug pressure eliminates drug susceptible parasites, allowing drug resistant parasites to overgrow [15].
Based on the exacerbation of PM by IPTp and the association between PM and risk of parasitemia during infancy, we hypothesized that maternal IPTp exposure might increase the risk of malaria infection and disease in their offspring. To test this hypothesis we evaluated the relationship between maternal IPTp use and risk of parasitemia and severe malaria in their offspring. We considered the possibility that the effects of IPTp might be restricted to offspring...