Intermittent screening and treatment with dihydroartemisinin-piperaquine and intermittent preventive therapy with sulfadoxine-pyrimethamine have similar effects on malaria antibody in pregnant Malawian women

Andrew Teo,Louise M Randall,Victor Mwapasa,Linda Kalilani Phiri,Amalia Karahalios,Stephen J Rogerson,Carole Khairallah,Feiko O Ter Kuile,David L Narum,Mwayiwawo Madanitsa,Christelle Buffet

doi:10.1038/s41598-019-44340-x

Abstract

In a randomised trial comparing intermittent screening and treatment (IST) with dihydroartemisinin-piperaquine (DP) and intermittent preventive therapy against malaria in pregnancy (IPT) with sulfadoxine-pyrimethamine (SP) in Malawi, the impacts of IST-DP and IPT-SP on the development and maintenance of malaria antibody immunity were compared. Pregnant Malawian women were randomised to receive IST-DP or IPT-SP. In a nested study, paired enrolment and delivery plasma samples from 681 women were assayed for antibodies against recombinant antigens and for IgG and opsonising antibodies to antigens found on infected erythrocytes (IEs). At delivery, antibody responses did not differ between study arms. Between enrolment and delivery, antibodies to recombinant antigens decreased, whereas antibodies to IEs including opsonising antibodies remained stable. Overall, changes in antibody responses over pregnancy did not differ by treatment arm. Stratifying by gravidity, antibody to schizont extract decreased more in multigravidae receiving IST-DP than IPT-SP. There was minimal impact of treatment arm on the development and maintenance of malaria immunity. While antibodies to recombinant antigens declined between enrolment and delivery, antibodies directed against IEs tended to be more stable, suggesting longer-lasting protection.Clinical trial registration: Pa n African Clinical Trials Registry (PACTR201103000280319) 14/03/2011. URL: http://www.isrctn.com/ISRCTN69800930.

Highlights

Malaria in pregnancy (MiP) increases the risk of mortality and morbidity in pregnant women and their infants[1]
When we examined antibody to infected erythrocytes (IEs), there was an increase in total IgG antibody to endothelial-binding IEs in the intermittent preventive therapy during pregnancy (IPT)-SP arm at delivery, but this association was absent for placental-binding IEs and in the intermittent screening and treatment (IST)-DP arm to both parasite strains, Fig. S1B
In the context of a randomised trial of IST-DP compared to IPT-SP in pregnant Malawian women, we investigated the effect of each treatment on antibody immunity to malaria, and determined whether IST-DP altered the development and maintenance of pregnancy-specific antibody immunity when compared to IPT-SP

Summary

Introduction

Malaria in pregnancy (MiP) increases the risk of mortality and morbidity in pregnant women and their infants[1]. Most studies of antibody responses have used samples collected during the last trimester or at delivery, but pregnant women begin to acquire antibody to placental-binding IEs early in first pregnancy[7,8], and the use of IPT-SP has been shown to slow acquisition of such immunity[9]. IST relies on RDT-based detection of infection and will not detect placental-sequestered parasites or submicroscopic infections, potentially exposing pregnant women to longer periods of parasitaemia than IPT. Whether this affects the development of pregnancy-specific immunity, or the maintenance of malaria immunity more generally, is unknown, but studies mainly in non-pregnant hosts show that antibody is important in clearance of malaria infection, including infections with drug-resistant parasites[10,11]. We compared antibody responses at study enrolment and delivery and change in antibody responses from enrolment to delivery by treatment arm, and evaluated the effect of malaria infection during pregnancy on antibody measurements

Methods

Results

Conclusion