Host iron status and erythropoietic response to iron supplementation determines susceptibility to the RBC stage of falciparum malaria during pregnancy

Morgan M. Goheen,Andrew M. Prentice,Rita Wegmüller,Hans Verhoef,Ebrima Danso,Amat Bah,Bakary Darboe,Carla Cerami

doi:10.1038/s41598-017-16896-z

Abstract

Anaemia and malaria are both common in pregnant women in Sub-Saharan Africa. Previous evidence has shown that iron supplementation may increase malaria risk. In this observational cohort study, we evaluated P. falciparum pathogenesis in vitro in RBCs from pregnant women during their 2nd and 3rd trimesters. RBCs were collected and assayed before (n = 327), 14 days (n = 82), 49 days (n = 112) and 84 days (n = 115) after iron supplementation (60 mg iron as ferrous fumarate daily). P. falciparum erythrocytic stage growth in vitro is reduced in anaemic pregnant women at baseline, but increased during supplementation. The elevated growth rates parallel increases in circulating CD71-positive reticulocytes and other markers of young RBCs. We conclude that Plasmodium growth in vitro is associated with elevated erythropoiesis, an obligate step towards erythroid recovery in response to supplementation. Our findings support current World Health Organization recommendations that iron supplementation be given in combination with malaria prevention and treatment services in malaria endemic areas.

Highlights

Malaria and anaemia are two common health problems facing pregnant women in Sub-Saharan Africa
The study population consisted of 498 healthy pregnant women identified in the Jarra West and Kiang East regions of rural Gambia who were estimated to be at 14–22 weeks gestation during recruitment, fit all enrolment criteria, and consented to participate[26]
We show P. falciparum growth decreases in red blood cells (RBCs) from anaemic (Hgb < 11 g/dl) pregnant Gambian women and that protection offered by anaemia in pregnant women in the second trimester of pregnancy is substantial (~11.7% change per standard deviation shift in haemoglobin)

Summary

Introduction

Malaria and anaemia are two common health problems facing pregnant women in Sub-Saharan Africa. Susceptibility peaks during the second trimester and risk remains elevated for up to 60 days post-partum It is highest in primagravida women, women of all gravidities have increased susceptibility to malaria. World Health Organization (WHO) guidelines recommend 30 to 60 mg elemental iron and 400 mg folic acid daily throughout pregnancy These recommendations are based on evidence showing that daily iron and folic acid reduces the risk of low birth weight, preterm birth, maternal anaemia and maternal iron deficiency[10]. We have systematically assessed P. falciparum growth in vitro in RBCs drawn from pregnant women before, during, and after 12 weeks of iron supplementation, which was initiated during the 2nd trimester of pregnancy. The women in this study did receive IPTp-SP, they donated blood for the malaria in vitro growth assays at each of the scheduled visits prior to ingestion of the monthly dose. We observe parasite growth increases with iron supplementation, paralleling increases in circulating young RBCs, and potentially representing a period of increased malaria susceptibility following iron supplementation of pregnant women

Methods

Results

Conclusion