Soluble urokinase-type plasminogen activator receptor as a prognostic marker of Ugandan children at risk of severe and fatal malaria

Authors

Veselina Stefanova, University of Toronto, Canada
Michelle Ngai, University Health Network, Canada
Andrea Weckman, University of Toronto, Canada
Julie Wright, Toronto General Hospital, Canada
Kathleen Zhong, Toronto General Hospital, Canada
Melissa Richard-Greenblatt, University of Toronto, Canada
Chloe McDonald, University of Toronto, Canada
Andrea Conroy, Indiana University, USA
Sophie Namasopo, Jinja Regional Referral Hospital,Uganda
Robert Opoka, Aga Khan UniversityFollow

Document Type

Article

Department

Paediatrics and Child Health (East Africa)

Abstract

Background: Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk-stratify children with malaria.

Methods: Plasma suPAR levels were determined in consecutive febrile children with malaria at presentation to hospital in Jinja, Uganda. We evaluated the accuracy of suPAR in predicting in-hospital mortality, and whether suPAR could improve a validated clinical scoring system (Lambaréné Organ Dysfunction Score [LODS]).

Results: Of the 1226 children with malaria, 39 (3.2%) died. suPAR concentrations at presentation were significantly higher in children who went on to die than in those who survived (P < .0001). suPAR levels were associated with disease severity (LODS: 0 vs 1, P = .001; 1 vs 2, P < .001; 2 vs 3, 0 vs 2, 1 vs 3, and 0 vs 3, P < .0001). suPAR concentrations were excellent predictors of in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.92 [95% confidence interval {CI}, .91–.94]). The prognostic accuracy of LODS (AUROC, 0.93 [95% CI, .91–.94]) was improved when suPAR was added (AUROC, 0.97 [95% CI, .96–.98]; P < .0001).

Conclusions

Conclusions: Measuring suPAR at presentation can identify children at risk of severe and fatal malaria. Adding suPAR to clinical scores could improve the recognition and triage of children at risk of death. suPAR can be detected with a point-of-care test and can now be evaluated in prospective trials.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Clinical Infectious Diseases

Recommended Citation

Stefanova, V., Ngai, M., Weckman, A., Wright, J., Zhong, K., Richard-Greenblatt, M., McDonald, C., Conroy, A., Namasopo, S., Opoka, R. (2023). Soluble urokinase-type plasminogen activator receptor as a prognostic marker of Ugandan children at risk of severe and fatal malaria. Clinical Infectious Diseases, 76(3), 1079-1086.
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_paediatr_child_health/237