Control of protein biomarker C5a may be linked to pregnancy-associated malaria, according to a study by Canadian researchers.
Another group of Canadian researchers determined that an imbalance between angiopoietin-1 and angiopoietin-2 may be associated with cerebral malaria.
The study of pregnancy-associated malaria was conducted on pregnant women in Kenya. The researchers determined that inflammatory peptide C5a levels were significantly higher in women who had placental malaria than in those who did not. The highest levels of C5a were observed in women with particularly high levels of placental parasites.
The researchers wrote that “in the presence of malaria toxin pfGPI, monocytes generate C5a and induce expression of C5a receptor (CD88).” These monocytes were co-cultivated by C5a and pfGPI and produced cytokines, chemokines and anti-angiogenic factor sFIt-1, according to the researchers. They wrote that this inflammatory response was abrogated by a C5a receptor blockade.
These findings demonstrated that C5a contributed to a poorly-regulated inflammatory and angiogenic response to pregnancy-associated malaria. They also showed that complementary activation may contribute to the pathogenesis of the disease.
Cerebral malaria findings
Poor understanding of validated biomarkers that predict the risk of cerebral malaria in patients with malaria prompted researchers to examine endothelial activation markers angiopoeitin-1 (ANG-1) and angiopoeitin-2 (ANG-2). The researchers examined serum samples in healthy controls and patients with Plasmodium falciparum who had uncomplicated or cerebral disease. The studies were conducted in adults from Thailand and children from Uganda.
Decreased ANG-1 levels were observed in both populations among patients with cerebral malaria compared with healthy controls and patients who had uncomplicated malaria (P<0.001). Both populations also demonstrated increased ANG-2 levels in patients with cerebral malaria versus healthy controls and patients with uncomplicated malaria (P<0.001). ANG-2 levels were not increased in patients with uncomplicated malaria versus healthy controls.
The researchers also evaluated patients and controls for tumor necrosis factor. Tumor necrosis factor was elevated in patients with malaria compared to healthy controls. However, significant elevations in tumor necrosis factor level was observed in cerebral versus uncomplicated malaria only in the Thai adult population (P<0.001).
Analysis of receiver operating curves demonstrated that the ratio of ANG-2 to ANG-1 was highly accurate in discriminating cerebral malaria patients from uncomplicated malaria patients in both populations, according to the researchers.
Lovegrove F. #1184.
Conroy A. #1187.
Presented at: ASTMH 57th Annual Meeting; Dec. 7-11, 2008; New Orleans.