Clinical Outcomes of Submicroscopic Infections and Correlates of Protection of VAR2CSA Antibodies in a Longitudinal Study of Pregnant Women in Colombia

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 where and cocirculate. 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 by , 33% were caused by, and 20% were caused by mixed spp. Mixed infections of and were associated with lower gestational age at delivery ( = 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 ( = 0.0086). SMIs occur frequently during pregnancy, and while mixed infections of both and were 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.

Malaria in Pregnancy in Endemic Regions of Colombia: High Frequency of Asymptomatic and Peri-Urban Infections in Pregnant Women with Malaria

“…In Colombia, MiP has been mainly studied in the north-west region of the country during 2005-2011, detecting a prevalence ranged between 1 and 13%; most of the cases were caused by P. vivax [ 12 , 19 , 28 ]. In those studies, MiP was associated with complicated malaria [ 30 ], low birth weight, and prematurity [ 31 ].…”

“…It is important to consider that there may be other factors associated with anaemia in this population, such as iron and/or folate deficiency and hookworm infection, which are prevalent in these settings [34][35][36]. A significant proportion of infected pregnant women carries subpatent parasitaemias that are not detected by routine test [11,12,14,27,28]. The clinical impact of asymptomatic and subpatent infections remains understood, and their importance needs to be investigated [3].…”

“…The clinical impact of asymptomatic and subpatent infections remains understood, and their importance needs to be investigated [3]. From the few studies in Latin America, there is no correlation between subpatent infections and poor pregnancy outcomes [27,28].…”

Submicroscopic Plasmodium infection during pregnancy is associated with reduced antibody levels to tetanus toxoid

“…There are no reports of maternal tetanus in South America or of levels of anti‐TT IgG. In the northwestern region of Colombia P. falciparum and P. vivax are endemic, and a high frequency of pregnancy‐associated submicroscopic plasmodial infections have been reported in peripheral blood during the course of pregnancy and in placental blood (23 and 4.9%, respectively) . Little is known about the effects of those infections on immunity in mothers and babies.…”

Evaluation of highly sensitive diagnostic tools for the detection of P. falciparum in pregnant women attending antenatal care visits in Colombia

“…Although microscopy remains the mainstay of malaria diagnosis in many endemic settings, this method provides limited sensitivity and requires well-trained personnel as well as adequate laboratory reagents and equipment. In Colombia, microscopy-based diagnosis has been shown to miss between 20 and 75% of maternal infections detected in peripheral blood by Polymerase Chain Reaction (PCR) [10][11][12][13][14][15]. RDTs are inexpensive and can be used by minimally trained health workers, offering therefore a useful alternative to microscopy [8,[16][17][18][19][20].…”