Developing a multivariate prediction model of antibody features associated with protection of malaria-infected pregnant women from placental malaria

开发与保护感染疟疾的孕妇免受胎盘疟疾感染相关的抗体特征的多变量预测模型

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作者:Elizabeth H Aitken #, Timon Damelang #, Amaya Ortega-Pajares #, Agersew Alemu, Wina Hasang, Saber Dini, Holger W Unger, Maria Ome-Kaius, Morten A Nielsen, Ali Salanti, Joe Smith, Stephen Kent, P Mark Hogarth, Bruce D Wines, Julie A Simpson, Amy W Chung #, Stephen J Rogerson #

Background

Plasmodium falciparum causes placental malaria, which

Conclusions

We have identified candidate antibody features that could accurately identify malaria-infected women as protected from placental infection. It is likely that there are multiple pathways to protection against placental malaria. Funding: This study was supported by the National Health and Medical Research Council (Nos. APP1143946, GNT1145303, APP1092789, APP1140509, and APP1104975).

Methods

We used a systems serology approach with elastic net-regularized logistic regression, partial least squares discriminant analysis, and a case-control study design to identify naturally acquired antibody features mid-pregnancy that were associated with protection from placental malaria at delivery in a cohort of 77 pregnant women from Madang, Papua New Guinea.

Results

The machine learning techniques selected 6 out of 169 measured antibody features towards VAR2CSA that could predict (with 86% accuracy) whether a woman would subsequently have active placental malaria infection at delivery. Selected features included previously described associations with inhibition of placental binding and/or opsonic phagocytosis of infected erythrocytes, and network analysis indicated that there are not one but multiple pathways to protection from placental malaria. Conclusions: We have identified candidate antibody features that could accurately identify malaria-infected women as protected from placental infection. It is likely that there are multiple pathways to protection against placental malaria. Funding: This study was supported by the National Health and Medical Research Council (Nos. APP1143946, GNT1145303, APP1092789, APP1140509, and APP1104975).

Trial registration

ClinicalTrials.gov NCT01136850.

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