title: Performance of C-reactive protein and procalcitonin to distinguish viral from bacterial and malarial causes of fever in Southeast Asia.
abstract: BACKGROUND
  Poor targeting of antimicrobial drugs contributes to the millions of deaths each year from malaria, pneumonia, and other tropical infectious diseases. While malaria rapid diagnostic tests have improved use of antimalarial drugs, there are no similar tests to guide the use of antibiotics in undifferentiated fevers. In this study we estimate the diagnostic accuracy of two well established biomarkers of bacterial infection, procalcitonin and C-reactive protein (CRP) in discriminating between common viral and bacterial infections in malaria endemic settings of Southeast Asia.
  
  
  METHODS
  Serum procalcitonin and CRP levels were measured in stored serum samples from febrile patients enrolled in three prospective studies conducted in Cambodia, Laos and, Thailand. Of the 1372 patients with a microbiologically confirmed diagnosis, 1105 had a single viral, bacterial or malarial infection. Procalcitonin and CRP levels were compared amongst these aetiological groups and their sensitivity and specificity in distinguishing bacterial infections and bacteraemias from viral infections were estimated using standard thresholds.
  
  
  RESULTS
  Serum concentrations of both biomarkers were significantly higher in bacterial infections and malaria than in viral infections. The AUROC for CRP in discriminating between bacterial and viral infections was 0.83 (0.81-0.86) compared with 0.74 (0.71-0.77) for procalcitonin (p < 0.0001). This relative advantage was evident in all sites and when stratifying patients by age and admission status. For CRP at a threshold of 10 mg/L, the sensitivity of detecting bacterial infections was 95% with a specificity of 49%. At a threshold of 20 mg/L sensitivity was 86% with a specificity of 67%. For procalcitonin at a low threshold of 0.1 ng/mL the sensitivity was 90% with a specificity of 39%. At a higher threshold of 0.5 ng/ul sensitivity was 60% with a specificity of 76%.
  
  
  CONCLUSIONS
  In samples from febrile patients with mono-infections from rural settings in Southeast Asia, CRP was a highly sensitive and moderately specific biomarker for discriminating between viral and bacterial infections. Use of a CRP rapid test in peripheral health settings could potentially be a simple and affordable measure to better identify patients in need of antibacterial treatment and part of a global strategy to combat the emergence of antibiotic resistance.
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. yoel@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. yoel@tropmedres.ac.
authors.forename: Yoel
authors.initials: Y
authors.lastname: Lubell
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. stuart@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. stuart@tropmedres.ac.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Blacksell
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. susie@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. susie@tropmedres.ac.
authors.forename: Susanna
authors.initials: S
authors.lastname: Dunachie
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. ampai@tropmedres.ac.
authors.forename: Ampai
authors.initials: A
authors.lastname: Tanganuchitcharnchai
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Thomas.A@tropmedres.ac.
authors.forename: Thomas
authors.initials: T
authors.lastname: Althaus
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. wanitda@tropmedres.ac.|Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. wanitda@tropmedres.ac.
authors.forename: Wanitda
authors.initials: W
authors.lastname: Watthanaworawit
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. parigi@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. parigi@tropmedres.ac.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Paris
authors.affiliation: Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. mayfong@tropmedres.ac.|Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane, Laos. mayfong@tropmedres.ac.|Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos. mayfong@tropmedres.ac.
authors.forename: Mayfong
authors.initials: M
authors.lastname: Mayxay
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. tom@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. tom@tropmedres.ac.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Peto
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. arjen@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. arjen@tropmedres.ac.
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. nickwdt@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. nickwdt@tropmedres.ac.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. nickd@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. nickd@tropmedres.ac.
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. francois@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. francois@tropmedres.ac.|Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. francois@tropmedres.ac.
authors.forename: François
authors.initials: F
authors.lastname: Nosten
authors.affiliation: Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. paul@tropmedres.ac.|Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane, Laos. paul@tropmedres.ac.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. pault@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. pault@tropmedres.ac.|Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia. pault@tropmedres.ac.
authors.forename: Paul
authors.initials: P
authors.lastname: Turner
mesh_terms: D000293:Adolescent; D000328:Adult; D001210:Asia, Southeastern / Q000453:epidemiology; D016470:Bacteremia / Q000175:diagnosis; D001424:Bacterial Infections / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis* / Q000378:metabolism; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D002160:Cambodia / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007812:Laos / Q000453:epidemiology; D008288:Malaria / Q000175:diagnosis; D008297:Male; D011014:Pneumonia / Q000175:diagnosis / Q000382:microbiology / Q000821:virology; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012680:Sensitivity and Specificity; D013785:Thailand / Q000453:epidemiology; D014777:Virus Diseases / Q000097:blood / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide