Table 2.
Examples of proteins and genes identified as associated with CM mortality.
| Molecule(s) | Role(s) | Sample Size | Location | Age Range | Main Findings |
|---|---|---|---|---|---|
| Chitinase-3-like protein 1 | Secreted glycoprotein expressed in inflammation and fibrosis | Fatal-CM (n = 23), Non-fatal CM (n = 80) | Uganda | 6 months to 12 y | Elevated plasma chitinase-3-like protein 1 expression was predictive of mortality in CM patients (AUC: 0.84 [95% CI 0.76–0.92]) [238]. |
| Angiopoietin-2 | Vascular growth factor | CM (n = 155) | Malawi | 6 months to 14 y | Elevated expression in fatal-CM (AOR 3.9 [95% CI 1.2–12.7], cut-point: > 3.85 ng/mL) [239]. |
| Tie-2 | Angiopoietin receptor | CM (n = 155) | Malawi | 6 months to 14 y | Elevated expression in fatal-CM (OR 3.2 [95% CI 1.6–6.3], cut-point: > 67.8 ng/mL) [239]. |
| Angiopoietin-1 | Vascular growth factor | CM (n = 155) | Malawi | 6 months to 14 y | Low expression associated with fatal-CM (OR 2.5 [95% CI 1.0–5.9]). Levels ≤ 6.76ng/mL were also associated with the presence of retinopathy (OR 5.9 [95% CI 2.7–12.8]) [239]. |
| UM (n = 67), CM (n = 69), Healthy (n = 28) | Uganda | 4 to 12 y | Low serum expression levels were associated with death in pediatric CM patients (median level in non-fatal CM: 9.1, range: 0.39–38; fatal CM: 0.39, range: 0.39–4.6; p -value: 0.027) [240]. | ||
| L-arginine | Protein biosynthesis and nitric oxide synthesis | CM (n = 39), Healthy (n = 19), UM (n = 17) | Tanzania | 1 to 8 y | Plasma levels < 45.4 µmol/L were associated with fatal-CM (OR 26.2, [95% CI 1.2–586] in multivariate analysis) [241]. |
| TNF-alpha2 allele (rs1800629) | Pro-inflammatory cytokine | Fatal-CM and sequelae (n = 99), non-fatal and no sequelae (n = 277) | Gambia | 1 to 10 y | Identified a RR of 7.7 for mortality in CM patients homozygous for this allele ([95% CI 1.9–30.0]) [198]. |
| Erythropoietin | Hematopoietic Factor | CM with plasma erythropoietin measured (n = 204) | Uganda | 18 months to 12 y | High plasma levels associated with more severe CM as characterized by longer coma and a 1.74-fold [95% CI 1.09–2.8] increase in mortality[156]. |
Legend
Abbreviations: Area Under the Curve (AUC); Adjusted Odds Ratio (AOR); Confidence Interval (CI); Cerebral Malaria (CM); Odds Ratio (OR); Relative Risk (RR); Uncomplicated Malaria (UM)