Systematic review of the role of angiopoietin-1 and angiopoietin-2 in Plasmodium species infections: biomarkers or therapeutic targets?

Sepsis is associated with significant mortality. Early diagnosis and prognosis of patients with sepsis is still a difficult clinical challenge. In this study, the ability of plasma PTX3 (pentraxin 3), MCP1 (monocyte chemoattractant protein 1) and Ang (angiopoietin)1/2 was investigated to evaluate the severity of sepsis. Blood samples were obtained from 43 patients with sepsis. A total of 33 post‐surgery patients with infections and 25 healthy individuals served as controls. The results showed that plasma PTX3, MCP1 and Ang2 significantly increased in patients on the first day of septic shock onset, while sepsis patients had significantly higher Ang2 level, compared with controls. Furthermore, PTX3, MCP1 and Ang2 had high AUROC values in patients with septic shock on the first day of sepsis onset. The findings suggest that PTX3, MCP1 and Ang2 maybe early predictors to evaluate the severity of sepsis and septic shock with the latest Sepsis 3.0 definitions.

Sepsis, a dysregulated host response to infection that causes life-threatening organ dysfunction, is a highly heterogeneous syndrome with no specific treatment. Although sepsis can be caused by a wide variety of pathogenic organisms, endothelial dysfunction leading to vascular leak is a common mechanism of injury that contributes to the morbidity and mortality associated with the syndrome. Perturbations to the angiopoietin (Ang)/Tie2 axis cause endothelial cell activation and contribute to the pathogenesis of sepsis. In this review, we summarize how the Ang/Tie2 pathway is implicated in sepsis and describe its prognostic as well as therapeutic utility in life-threatening infections.

Severe malaria (SM) has high mortality and morbidity rates despite treatment with potent antimalarials. Disease onset and outcome is dependent upon both parasite and host factors. Infected erythrocytes bind to host endothelium contributing to microvascular occlusion and dysregulated inflammatory and immune host responses, resulting in endothelial activation and microvascular damage. This review focuses on the mechanisms of host endothelial and microvascular injury. Only a small percentage of malaria infections (≤1%) progress to SM. Early recognition and treatment of SM can improve outcome, but we lack triage tools to identify SM early in the course of infection. Current point-of-care pathogen-based rapid diagnostic tests do not address this critical barrier. Immune and endothelial activation have been implicated in the pathobiology of SM. We hypothesize that measuring circulating mediators of these pathways at first clinical presentation will enable early triage and treatment of SM. Moreover, that host-based interventions that modulate these pathways will stabilize the microvasculature and improve clinical outcome over that of antimalarial therapy alone. ARTICLE HISTORY