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ANTIBODY RESPONSE TO THE PLASMODIUM FALCIPARUM ANTIGEN VAR2CSA IN PREGNANT WOMEN RESIDING IN MALARIA ENDEMIC AREAS

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Title:ANTIBODY RESPONSE TO THE PLASMODIUM FALCIPARUM ANTIGEN VAR2CSA IN PREGNANT WOMEN RESIDING IN MALARIA ENDEMIC AREAS
Authors:Lloyd, Yukie Michelle
Contributors:Taylor, Diane W. (advisor)
Biomed Science (Tropical Medicine) (department)
Keywords:Immunology
Microbiology
Molecular biology
antibody
Cameroon
show 4 moreCSA
placental malaria
Plasmodium falciparum
VAR2CSA
show less
Date Issued:Dec 2018
Publisher:University of Hawaiʻi at Mānoa
Abstract:In malaria endemic countries, placental malaria (PM) has detrimental consequences for both the mother and her baby. PM is caused when Plasmodium falciparum-infected erythrocytes bind to chondroitin sulfate A (CSA) in the intervillous space in the placenta and sequestrate, leading to excessive inflammation and adverse pregnancy outcomes; such as maternal anemia, premature deliveries and low birthweight babies. Fortunately, pregnant women in malaria endemic areas produce antibodies (Ab) to VAR2CSA and they are associated with improved pregnancy outcomes. Majority of the studies on Ab to VAR2CSA have been conducted in high malaria transmission areas, with very few studies in low- or extremely low transmission areas. Because of the global decline in malaria transmission due to improved prevention methods, high transmission areas are becoming low transmission areas. Although the presence of Ab to VAR2CSA seems to be crucial to protect women from PM in high transmission areas, information on the precise functions of Ab to VAR2CSA and if they are necessary in low transmission areas remain unclear. In this study, Ab to VAR2CSA were evaluated for their association with absence of PM and improved pregnancy outcomes in a low transmission area. Furthermore, four major assays that measure Ab levels, Ab avidity, opsonic phagocytosis and inhibition-of-binding were compared to determine whether data from the assays were associated with each other, and which assays results were associated with absence of PM or improved pregnancy outcomes. Two novel bead-based assays were developed and employed to measure the effector functions of VAR2CSA Ab. The data showed that women with PM had higher Ab levels than women without PM. Thus, the presence of Ab to VAR2CSA was not associated with absence of PM, but in fact indicated placental infection. However, women who had PM benefited from having Ab to VAR2CSA by reducing their likelihood of high placental parasitemia (OR= 0.43; 95% CI: 0.27 to 0.69) and low birthweight babies (OR= 0.44; 95% CI: 0.25 to 0.80). In women who had Ab to VAR2CSA at delivery, Ab levels to VAR2CSA positively correlated with opsonic phagocytosis (r=0.403, p<0.001) and Ab avidity (r=0.351, p<0.0001), and inversely correlated with inhibition-of-binding, shown as the percentage of VAR2CSA-coupled beads remained bound to CSA-coupled beads (r=-0.464, p<0.0001). An increase in Ab avidity and increased baby birthweight (p=0.033) was the only assay and pregnancy outcome that showed statistical significance. For example, women who had more than 35% high avidity Ab to VAR2CSA had babies that averaged (±SEM) 204.6±88.6 grams more than women with <15% high avidity (p=0.022). Inhibition-of-binding was marginally associated with increased baby birthweight (p=0.088). Overall, these data reinforce the importance of Ab to VAR2CSA in a low-transmission area and present the first evidence that, among women who had detectable levels of Ab to VAR2CSA at delivery, Ab avidity was the only quality that was associated with improved baby birthweight.
Description:Ph.D. Thesis. University of Hawaiʻi at Mānoa 2018.
Pages/Duration:129 pages
URI:http://hdl.handle.net/10125/62051
Rights:All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
Appears in Collections: Ph.D. - Biomedical Sciences (Tropical Medicine)


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