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The role of volatile organic compounds as predictors of treatment response in drug susceptible TB patients: An initial proof of concept study

      To eliminate Tuberculosis (TB), we need shorter and effective treatment regimens. The World Health Organization (WHO) defines ‘cured TB’ as: “A pulmonary TB patient with bacteriologically confirmed TB at the beginning of treatment who was smear- or culture-negative in the last month of treatment and on at least one previous occasion”. At present, for drug susceptible TB, culture conversion at two months of treatment is used as a primary surrogate endpoint for treatment response
      • Aber V.R.
      • Nunn A.J.
      [Short term chemotherapy of tuberculosis. Factors affecting relapse following short term chemotherapy].
      , which is often debated because of weak correlation with treatment outcomes. Valid early surrogate markers could help in predicting long-term treatment outcomes, reduce costs and time, and revolutionize TB treatment.
      • Nahid P.
      • Saukkonen J.
      • Mac Kenzie W.R.
      • Johnson J.L.
      • Phillips P.P.
      • Andersen J.
      • et al.
      CDC/NIH Workshop. Tuberculosis biomarker and surrogate endpoint research roadmap.
      ,
      • Nahid P.
      • Dorman S.E.
      • Alipanah N.
      • Barry P.M.
      • Brozek J.L.
      • Cattamanchi A.
      • et al.
      Official American thoracic society/centers for disease control and prevention/infectious diseases society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis.
      Exhaled breath, composed of volatile organic compounds (VOCs), might have potential to reflect disease activity. These ‘smell prints’, picked up by an electronic nose (eNose) device, are either VOCs from the host, the pathogen or their interplay.
      • Phillips M.
      • Basa-Dalay V.
      • Blais J.
      • Bothamley G.
      • Chaturvedi A.
      • Modi K.D.
      • et al.
      Point-of-care breath test for biomarkers of active pulmonary tuberculosis.
      ,
      • Zetola N.M.
      • Modongo C.
      • Matsiri O.
      • Tamuhla T.
      • Mbongwe B.
      • Matlhagela K.
      • et al.
      Diagnosis of pulmonary tuberculosis and assessment of treatment response through analyses of volatile compound patterns in exhaled breath samples.
      In an earlier study, the Aeonose™ showed excellent performance in differentiating healthy persons from TB patients, with a sensitivity and specificity of 91% and 93%, respectively.
      • Coronel Teixeira R.
      • Rodriguez M.
      • Jimenez de Romero N.
      • Bruins M.
      • Gomez R.
      • Yntema J.B.
      • et al.
      The potential of a portable, point-of-care electronic nose to diagnose tuberculosis.
      This study investigated if smell print samples in TB patients have potential in predicting treatment response and its possible confounders, aiming to explore the utility of VOCs as an early biomarker in TB treatment.
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