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Assessing Heterogeneity of the Immune Response to Malaria in African Children

Hannon, Emily Rae
http://orcid.org/0000-0003-1905-7544
http://rave.ohiolink.edu/etdc/view?acc_num=case1727811264223224

Abstract Details

2025, Doctor of Philosophy, Case Western Reserve University, Epidemiology and Biostatistics.
Malaria remains a global health challenge with over 600,000 deaths annually. Ninety-five percent of the global malaria burden occurs in children living in sub-Saharan Africa. In regions with moderate to high mosquito-borne transmission of Plasmodium falciparum, the most lethal of the 5 Plasmodium species that infect humans, children are repeatedly infected and by age 10 to 12 years develop naturally acquired immunity (NAI). NAI is characterized by protection from symptomatic febrile illness and severe malaria that can lead to death. However, NAI does not protect against chronic asymptomatic blood stage infections that serve as a major reservoir of transmission by local mosquito vectors. Current evidence indicates that host inflammatory responses and the progressive development of NAI in African children is heterogeneous that is, in part, due to genetic polymorphisms, ecologic factors such as residence near mosquito breeding sites, and the use of insecticidal bed nets among other factors. This heterogeneity is relatively unexplored with respect to the innate and adaptive immune mechanisms that underlie NAI. To address this gap in knowledge, we evaluated cellular and molecular responses of African children at healthy baseline, during acute febrile (“uncomplicated”) Plasmodium falciparum malaria, and upon recovery in whole blood of 40 children from Burkina Faso and peripheral blood mononuclear cells of 8 children from Kenya. Cell-type proportion estimates were obtained by deconvolution using RNA sequencing and genome-wide DNA methylation data. Unsupervised learning algorithms identified two distinct immune response groups in children, designated as Type 1 and Type 2, from both Burkina Faso and Kenya. The response designation was based on patterns of cell-type proportions, DNA methylation and gene expression. The two types were predominantly quantitative, with response Type 2 exhibiting larger changes of cell type counts, DNA methylation and gene expression from asymptomatic baseline to acute malaria and from baseline to recovery. The two responses did not differ with regard to blood stage Plasmodium falciparum density, age or sex. In depth knowledge of the immune mechanisms and susceptibility to future infections and clinical malaria for these two response types and their relevance to acquisition and maintenance of NAI requires additional longitudinal cohort studies.
Catherine Stein (Committee Chair)
Scott Williams (Advisor)
James Kazura (Advisor)
Arlene Dent (Committee Member)
Mark Cameron (Committee Member)
159 p.
Immunology; Molecular Biology
DNA methylation; Transcriptome; Malaria; Immunology; Pediatric; Africa

Recommended Citations

Citations

  • Hannon, E. R. (2025). Assessing Heterogeneity of the Immune Response to Malaria in African Children [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1727811264223224

    APA Style (7th edition)

  • Hannon, Emily. Assessing Heterogeneity of the Immune Response to Malaria in African Children. 2025. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1727811264223224.

    MLA Style (8th edition)

  • Hannon, Emily. "Assessing Heterogeneity of the Immune Response to Malaria in African Children." Doctoral dissertation, Case Western Reserve University, 2025. http://rave.ohiolink.edu/etdc/view?acc_num=case1727811264223224

    Chicago Manual of Style (17th edition)

case1727811264223224
44
© 2025, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.