RÉSUMÉ
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 Plasmodium falciparum and Plasmodium vivax 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 P. falciparum, 33% were caused by P. vivax, and 20% were caused by mixed Plasmodium spp. Mixed infections of P. falciparum and P. vivax were 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 both P. falciparum and P. vivax 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.
RÉSUMÉ
BACKGROUND: Dengue fever and leptospirosis have partially overlapping geographic distributions, similar clinical presentations and potentially life-threatening complications but require different treatments. Distinguishing between these cosmopolitan emerging pathogens represents a diagnostic dilemma of global importance. We hypothesized that perturbations in host biomarkers can differentiate between individuals with dengue fever and leptospirosis during the acute phase of illness. METHODS: We randomly selected subjects from a prospective cohort study of acute febrile illness in Bucaramanga, Colombia and tested 19 serum biomarkers by ELISA in dengue fever (DF, n = 113) compared to subjects with leptospirosis (n = 47). Biomarkers were selected for further analysis if they had good discriminatory ability (area under the ROC curve (AUC) >0.80) and were beyond a reference range (assessed using local healthy controls). RESULTS: Nine biomarkers differed significantly between dengue fever and leptospirosis, with higher levels of Angptl3, IL-18BP, IP-10/CXCL10, Platelet Factor 4, sICAM-1, Factor D, sEng and sKDR in dengue and higher levels of sTie-2 in leptospirosis (p < 0.001 for all comparisons). Two biomarkers, sEng and IL18BP, showed excellent discriminatory ability (AUROC >0.90). When incorporated into multivariable models, sEng and IL18BP improved the diagnostic accuracy of clinical information alone. CONCLUSIONS: These results suggest that host biomarkers may have utility in differentiating between dengue and leptospirosis, clinically similar conditions of different etiology.