Calprotectin as a Biomarker for Melioidosis Disease Progression and Management

Author:

Natesan Mohan1,Corea Enoka2,Krishnananthasivam Shivankari3,Sathkumara Harindra Darshana3,Dankmeyer Jennifer L.4,Dyas Beverly K.1,Amemiya Kei4,De Silva Aruna Dharshan35,Ulrich Robert G.16

Affiliation:

1. Division of Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA

2. Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka

3. Genetech Research Institute, Colombo, Sri Lanka

4. Division of Bacteriology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA

5. Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, La Jolla, California, USA

6. Division of Virology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA

Abstract

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 < 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.

Funder

Army Medical Research Acquisition Activity

DOD | Defense Threat Reduction Agency

Publisher

American Society for Microbiology

Subject

Microbiology (medical)

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