Evaluating the predictive performance of malaria antibodies and FCGR3B gene polymorphisms on Plasmodium falciparum infec
- PDF / 1,391,952 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 58 Downloads / 205 Views
Malaria Journal Open Access
RESEARCH
Evaluating the predictive performance of malaria antibodies and FCGR3B gene polymorphisms on Plasmodium falciparum infection outcome: a prospective cohort study Duah Dwomoh1* , Bright Adu2, Daniel Dodoo2, Michael Theisen3,4,5, Samuel Iddi6 and Thomas A. Gerds7
Abstract Background: Malaria antigen-specific antibodies and polymorphisms in host receptors involved in antibody functionality have been associated with different outcomes of Plasmodium falciparum infections. Thus, to identify key prospective malaria antigens for vaccine development, there is the need to evaluate the associations between malaria antibodies and antibody dependent host factors with more rigorous statistical methods. In this study, different statistical models were used to evaluate the predictive performance of malaria-specific antibodies and host gene polymorphisms on P. falciparum infection in a longitudinal cohort study involving Ghanaian children. Methods: Models with different functional forms were built using known predictors (age, sickle cell status, blood group status, parasite density, and mosquito bed net use) and malaria antigen-specific immunoglobulin (Ig) G and IgG subclasses and FCGR3B polymorphisms shown to mediate antibody-dependent cellular functions. Malaria antigens studied were Merozoite surface proteins (MSP-1 and MSP-3), Glutamate Rich Protein (GLURP)-R0, R2, and the Apical Membrane Antigen (AMA-1). The models were evaluated through visualization and assessment of differences between the Area Under the Receiver Operating Characteristic Curve and Brier Score estimated by suitable internal cross-validation designs. Results: This study found that the FCGR3B-c.233C>A genotype and IgG against AMA1 were relatively better compared to the other antibodies and FCGR3B genotypes studied in classifying or predicting malaria risk among children. Conclusions: The data supports the P. falciparum, AMA1 as an important malaria vaccine antigen, while FCGR3Bc.233C>A under the additive and dominant models of inheritance could be an important modifier of the effect of malaria protective antibodies. Keywords: Apical membrane antigen 1, FCGR3B gene polymorphisms, Area under the receiver operating characteristic curve, Brier score, Bootstrap-validation, Calibration, Discrimination, Malaria, Antibodies, Antigenes
*Correspondence: [email protected] 1 Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana Full list of author information is available at the end of the article
Background Malaria remains a major public health concern globally and is considered as one of the most prevalent and lethal human infectious diseases among children in sub-Saharan Africa [1]. Despite the drastic reduction in the number of malaria cases and deaths in all ages globally, it still accounts for 10% of child deaths in sub-Saharan Africa [1], and mortality is mostly higher among children below
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 Intern
Data Loading...
