Performance Characteristics of Combinations of Host Biomarkers to Identify Women with Occult Placental Malaria: A Case-Control Study from Malawi
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BACKGROUND: Because of its propensity to sequester in the placental intervillous space, Plasmodium falciparum can evade detection by peripheral smear in women with placental malaria (PM). We evaluated host biomarkers as potential indicators of occult PM infections. METHODS AND FINDINGS: Using a case-control design, we evaluated the ability of biomarkers to identify PM in the absence of circulating peripheral parasites (n = 24) compared to placental smear-negative controls (n = 326). We measured levels of biomarkers (C3a, C5a, CRP, angiopoietin-1, angiopoietin-2, sTie-2, sEndoglin, VEGF, sFlt-1, tissue factor, and leptin) in maternal peripheral plasma at delivery. Using ROC curve analysis, we assessed the ability of clinical parameters and biomarkers to accurately detect PM infections identified by placental smear. We show that decreases in sFlt-1 and leptin and increases in CRP were associated with occult PM infections (p<0.01) and correlated with placental parasitaemia (p<0.01). Individually, all markers had moderate ability to diagnose occult PM infections with areas under the ROC between 0.62 and 0.72. In order to improve diagnostic performance, we generated simple scoring systems to identify PM infections using either a clinical score (0-2), a biomarker score (0-3) or a clinical plus biomarker score (0-5). The combinatorial model that incorporated both clinical parameters and biomarkers had an area under curve (AUC) of 0.85 (95% CI, 0.81-0.89), which was significantly better at identifying occult PM infections than the clinical score alone (p = 0.001). CONCLUSION: These data suggest that host biomarkers in the maternal peripheral blood may improve the detection of PM in the absence of peripheral parasitaemia.
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Other proposed biomarkers to detect PM include a combination of three markers (sFlt1, leptin and C-reactive protein).
“Other proposed biomarkers to detect PM include a combination of three markers (sFlt1, leptin and C-reactive protein) [82]”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [82]
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- Authors
- Conroy, A. L., Liles, W. C., Molyneux, M. E., Rogerson, S. J., & Kain, K. C.
- Affiliations
- University Health Network (CA)
- University of Liverpool (GB)
- The Royal Melbourne Hospital (AU)
- Corresponding author
- Kain, Kevin C.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-12-12
- Volume
- 6
- Issue
- 12
- Pages
- e28540
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3236186
- OpenAlex
- W2022870680
- Cited by
- 46
- References
- 29
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 7 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 3 · 2013: 8 · 2012: 4
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Greater South Information System
- Funders
- Genome Canada
- Wellcome Trust
- Ontario Genomics
- Ontario Genomics Institute
- Canada Research Chairs (MOP-115160, 13721)
- Canadian Institutes of Health Research (MOP- 13721, 115160, 13721, 115160_1)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
- Keywords
- placental malaria, host biomarkers, Plasmodium falciparum, soluble fms-like tyrosine kinase-1, leptin, C-reactive protein, angiopoietin-1, angiopoietin-2, vascular endothelial growth factor, tissue factor, diagnostic scoring system, maternal peripheral blood, Malawi
- MeSH terms
- Adolescent, Adult, C-Reactive Protein, Female, Humans, Malawi, Placenta, Pregnancy, Biomarkers, Case-Control Studies, Malaria, Falciparum, Leptin, Vascular Endothelial Growth Factor Receptor-1, Young Adult
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