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Clinical outcomes of submicroscopic infections and correlates of protection of VAR2CSA antibodies in a longitudinal study of pregnant women in Colombia

  • Kenneth Gavina
  • , Sedami Gnidehou
  • , Eliana Arango
  • , Chloe Hamel-Martineau
  • , Catherine Mitran
  • , Olga Agudelo
  • , Carolina Lopez
  • , Aisha Karidio
  • , Shanna Banman
  • , Jaime Carmona-Fonseca
  • , Ali Salanti
  • , Nicaise Tuikue Ndam
  • , Michael Hawkes
  • , Amanda Maestre
  • , Stephanie K Yanow

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Malaria in pregnancy can cause serious adverse outcomes for the mother and the fetus. However, little is known about the effects of submicroscopic infections (SMIs) in pregnancy, particularly in areas wherePlasmodium falciparumandPlasmodium vivaxcocirculate. A cohort of 187 pregnant women living in Puerto Libertador in northwest Colombia was followed longitudinally from recruitment to delivery. Malaria was diagnosed by microscopy, reverse transcription-quantitative PCR (RT-qPCR), and placental histopathology. Gestational age, hemoglobin concentration, VAR2CSA-specific IgG levels, and adhesion-blocking antibodies were measured during pregnancy. Statistical analyses were performed to evaluate the impact of SMIs on birth weight and other delivery outcomes. Twenty-five percent of women (45/180) were positive for SMIs during pregnancy. Forty-seven percent of infections (21/45) were caused byP. falciparum, 33% were caused byP. vivax, and 20% were caused by mixedPlasmodiumspp. Mixed infections ofP. falciparumandP. vivaxwere associated with lower gestational age at delivery (P= 0.0033), while other outcomes were normal. Over 60% of women had antibodies to VAR2CSA, and there was no difference in antibody levels between those with and without SMIs. The anti-adhesion function of these antibodies was associated with protection from SMI-related anemia at delivery (P= 0.0086). SMIs occur frequently during pregnancy, and while mixed infections of bothP. falciparumandP. vivaxwere not associated with a decrease in birth weight, they were associated with significant risk of preterm birth. We propose that the lack of adverse delivery outcomes is due to functional VAR2CSA antibodies that can protect pregnant women from SMI-related anemia.

OriginalsprogEngelsk
Artikelnummere00797-17
TidsskriftInfection and Immunity
Vol/bind86
Udgave nummer4
ISSN0019-9567
DOI
StatusUdgivet - 1 apr. 2018

Finansiering

We are grateful to the pregnant women and field staff for their participation in this work. We thank Momar Ndao, from the National Reference Centre for Parasitology, Montreal, Canada, for assisting with external quality assessment (EQA) for microscopy in Colombia. We thank Sandra Shokoples, Diana Gonzalez, Jahanara Rajwani, and Evelyn Medawar for assistance in the laboratory. CS2 parasites were obtained through the Malaria Research and Reference Reagent Resource Center (MR4) and were deposited by Stephen Rogerson. We also thank Michael Good for providing helpful feedback and comments on the manuscript. We declare that we have no conflicts of interest. This work was supported by the following: an Open Operating Grant from the Canadian Institutes of Health Research (CIHR), COLCIENCIAS (Colombia), the Universi-dad de Antioquia (Estrategia de Sostenibilidad 2014 –2015; Colombia), a PhD scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC) Create Host-Parasite Interactions Network, and graduate scholarships from the University of Alberta to K.G.; a Frederick Banting and Charles Best Canada Graduate Scholarship from CIHR, a graduate scholarship from the NSERC, and graduate scholarships from the University of Alberta to C.M.; an Emerging Leaders of the Americas scholarship to O.A.; and a generous donation from D. Davis.

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