Cytomegalovirus reactivation and acute and chronic complications in children with cerebral malaria: a prospective cohort study

Abstract

Background: Virus co-infection or reactivation may modify the host response during cerebral malaria. Cytomegalovirus (CMV) DNAemia has been associated with increased morbidity and mortality in adults with sepsis; however, the impact of CMV DNAemia on adverse outcomes in children with cerebral malaria is unknown. Methods: Clinical, physiological, and neurocognitive outcomes were compared in children aged 18 months to 12 years with cerebral malaria (N = 242) based on the presence or absence of CMV DNAemia 24 h after admission. The primary study outcome was subsequent in-hospital mortality. Secondary outcomes included the presence of acute kidney injury, neurocognitive impairment over a 2-year follow-up, and chronic kidney disease at the 1-year follow-up. Markers of platelet and endothelial cell activation and oxidative and nitrosative stress were measured to characterize the mechanisms by which CMV DNAemia might contribute to pathogenesis. Results: CMV DNAemia was present in 33 children with cerebral malaria (13.6%) 24 h after admission. CMV DNAemia was not significantly associated with mortality in this study. Children with CMV-DNAemia had a higher prevalence of acute kidney injury than those without CMV-DNAemia (59.4% vs. 38.6%, p = 0.03). There was no difference in the prevalence of chronic kidney disease or long-term neurocognitive impairment based on the presence of DNAemia. CMV DNAemia was associated with elevated plasma levels of P-selectin, angiopoietin-1, asymmetric dimethylarginine, and platelet counts. Conclusions: In children with cerebral malaria, CMV DNAemia is associated with acute kidney injury but not in-hospital mortality, chronic kidney disease, or long-term neurocognitive impairment.