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. 2025 Jul 8:15:1594088.
doi: 10.3389/fcimb.2025.1594088. eCollection 2025.

Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study

Bernard N Kanoi  1 , Harrison Waweru  1 , Francis M Kobia  1 , Joseph Mukala  2 , Peter Kirira  3 , Dominic Mogere  2 , Radiosa Gallini  4 , Mikael Åberg  5 , Manu Vatish  6 , Jesse Gitaka  1 , Masood Kamali-Moghaddam  4
Affiliations

Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study

Bernard N Kanoi et al. Front Cell Infect Microbiol. .

Abstract

Introduction: Pregnant women in sub-Saharan Africa face heightened susceptibility to Plasmodium falciparum malaria, with placental sequestration driving adverse outcomes. The infection may lead to pregnancy-associated malaria (PAM) because of the sequestration of Plasmodium falciparum-infected erythrocytes in the placental intervillous space. Although there are several tools for diagnosing malaria infection during pregnancy, including blood smear microscopic examination, rapid diagnostic tests, and PCR, there are no tools for detecting placental infection and, by extension, any dysfunction associated with PAM. Thus, PAM, specifically placental infection, can only be confirmed via postnatal placental histopathology. Therefore, there is an urgent need for specific plasma biomarkers of PAM.

Methods: Here, we used the high throughput proximity extension assay to screen plasma from malaria-exposed pregnant women for differentially expressed proteins that may serve as candidate biomarkers of Plasmodium falciparum infection during pregnancy, with future potential to inform diagnosis of PAM or adverse malaria outcomes. Such biomarkers may also elucidate the pathophysiology of PAM.

Results: Using proximity extension assay (PEA), we identified elevated IgG Fc receptor IIb (FCGR2B) and heme oxygenase-1 (HO-1) in malaria-positive pregnancies, while neurturin (NRTN) and IL-20 were downregulated.

Discussion: IL-20 emerged as a top candidate biomarker, warranting validation in large cohorts with placental histopathology.

Keywords: Plasmodium falciparum; biomarkers; malaria in pregnancy; pregnancy-associated malaria; proteomics; proximity extension assay (PEA).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Differential protein expression in malaria positive vs. malaria negative women. The title represents protein Uniprot acronym and ID. Relative PEA counts, represented as protein expression levels that are derived from reactivity NPX/LOD, to allow protein-to-protein comparison. *Represent statistical difference between malaria positive and negative groups (Kruskal Wallis, P < 0.05).
Figure 2
Figure 2
Kinetics of protein expression in malaria positive vs. malaria negative women at three time points during the pregnancy – 1st (red), 2nd (green) and 3rd Visit (blue). *Represent statistical difference between hospital visits, (Kruskal Wallis, P < 0.05). Relative PEA counts, represented as protein expression levels.
Figure 3
Figure 3
ROC curves for different protein expression levels in malaria positive vs. malaria negative women. Each protein has been assigned a color code, as indicated in the legend. Dashed diagonal line represents the line of no discrimination (AUC =0.5).
Figure 4
Figure 4
This figure summarizes the approach applied to identify plasma biomarkers of malaria during pregnancy leveraging a high-throughput multiplex PEA, that utilizes minute amount of blood sample.
See this image and copyright information in PMC

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