Calprotectin as a Biomarker for Melioidosis Disease Progression and Management.
Melioidosis is a neglected tropical disease that is caused by the bacteriumBurkholderia pseudomalleiand 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 ofB. pseudomalleiinfections 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.
Division of Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA mohan.natesan.ctr@mail.mil robert.g.ulrich.civ@mail.mil.
Mohan
M
Natesan
Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
Enoka
E
Corea
Genetech Research Institute, Colombo, Sri Lanka.
Shivankari
S
Krishnananthasivam
Genetech Research Institute, Colombo, Sri Lanka.
Harindra Darshana
HD
Sathkumara
Division of Bacteriology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
Jennifer L
JL
Dankmeyer
Division of Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
Beverly K
BK
Dyas
Division of Bacteriology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
Kei
K
Amemiya
Genetech Research Institute, Colombo, Sri Lanka.|Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, La Jolla, California, USA.
Aruna Dharshan
AD
De Silva
Division of Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA mohan.natesan.ctr@mail.mil robert.g.ulrich.civ@mail.mil.|Division of Virology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
Robert G
RG
Ulrich
D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D018450:Disease Progression; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D008297:Male; D008554:Melioidosis / Q000175:diagnosis* / Q000188:drug therapy; D008875:Middle Aged; D011247:Pregnancy; D044967:Serum / Q000737:chemistry; D055815:Young Adult
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D002097:C-Reactive Protein
Burkholderia pseudomallei; antibiotic; biomarker; calprotectin; melioidosis