Calprotectin as a Biomarker for Melioidosis Disease Progression and Management

Abstract

Melioidosis is a neglected tropical disease that is caused by the bacterium Burkholderia pseudomallei and is underreported in many countries where the disease is endemic. A long and costly administration of antibiotics is needed to clear infections, and there is an unmet need for biomarkers to guide antibiotic treatment and increase the number of patients that complete therapy. We identified calprotectin as a lead biomarker of B. pseudomallei infections and examined correlations between this serum protein and the antibiotic treatment outcomes of patients with melioidosis. Serum levels of calprotectin and C-reactive protein were significantly higher in patients with melioidosis and nonmelioidosis sepsis than in healthy controls. Median calprotectin levels were higher in patients with melioidosis than in those with nonmelioidosis sepsis, whereas C-reactive protein levels were similar in both groups. Notably, intensive intravenous antibiotic treatment of patients with melioidosis resulted in lower levels of calprotectin and C-reactive protein (P Ͻ 0.0001), coinciding with recovery. The median percent reduction of calprotectin and C-reactive protein was 71% for both biomarkers after antibacterial therapy. In contrast, we found no significant differences in calreticulin levels between the two melioidosis treatment phases. Thus, reductions in serum calprotectin levels were linked to therapeutic responses to antibiotics. Our results suggest that calprotectin may be a sensitive indicator of melioidosis disease activity and illustrate the potential utility of this biomarker in guiding the duration of antibiotic therapy.

An increase in p62/NBR1 levels in melioidosis patients of Sri Lanka exhibit a characteristic of potential host biomarker

“…Patient enrolment and clinical characteristics of the study population included here were partly reported elsewhere [ 28 ]. Clinical samples were collected over a period of 2 years (2013–2015).…”

“…Melioidosis patients older than 18 years were enrolled in this study as described elsewhere [ 28 ] . Clinical samples, matched PBMCs and sera were collected over a period of 2 years (2013–2015) from acute and confirmed cases of melioidosis during the antibiotic treatment phase.…”

“…Clinical samples, matched PBMCs and sera were collected over a period of 2 years (2013–2015) from acute and confirmed cases of melioidosis during the antibiotic treatment phase. Control sera were collected from non-melioidosis sepsis patients and healthy volunteers as described previously [ 28 ]. Ethics approval was obtained from the Ethics Review Committee, Faculty of Medicine, University of Colombo, Sri Lanka; Office of Human Use and Ethics (OHU and E) of U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), and U.S. Army Medical Research and Material Command (Office of Research Protection- Human Research Protection Office (USAMRMC-ORP-HRPO).…”

“…Patients with unknown fever origin (pneumonia, sepsis and abscess) were selected for B. pseudomallei screening. B. pseudomallei from blood and other patient specimens was isolated using specialized culture techniques and real-time (RT)-PCR assay as previously described [ 28 ]. The RT-PCR probes used were the Salmonella typhimurium lpxO gene, targeting a homologue gene to B. pseudomallei , Yersinia -like fimbrial (YLF) and Burkholderia thailandensis -like flagellum and chemotaxis (BTFC) gene clusters, as previously described [ 13 ].…”

“…Clinical samples, matched PBMCs and sera were collected over a period of 2 years (2013-2015) from acute and confirmed cases of melioidosis during the antibiotic treatment phase. Control sera were collected from non-melioidosis sepsis patients and healthy volunteers as described previously [28].…”