Combining host-derived biomarkers with patient characteristics improves signature performance in predicting tuberculosis treatment outcomes

Communications Biology, vol. 3, pp. 359

Abstract

Tuberculosis (TB) is a global health concern. Treatment is prolonged, and patients on anti-TB therapy (ATT) often experience treatment failure for various reasons. There is an urgent need to identify signatures for early detection of failure and initiation of a treatment switch.We investigated how gene biomarkers and/or basic patient characteristics could be used to define signatures for treatment outcomes in Indian adult pulmonary-TB patients treated with standard ATT. Using blood samples at baseline, a 12-gene signature combined with information on gender, previously-diagnosed TB, severe thinness, smoking and alcohol consumption was highly predictive of treatment failure at 6 months. Likewise a 4-protein biomarker signature combined with the same patient characteristics was almost as highly predictive of treatment failure. Combining biomarkers and basic patient characteristics may be useful for predicting and hence identification of treatment failure at an early stage of TB therapy.

Authors 10

1. Dhanasekaran Sivakumaran

   Haukeland University Hospital · University of Bergen

   Affiliation as printed

   Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway

   Department of Microbiology, Haukeland University Hospital, University of Bergen, Bergen, Norway

2. Synne Jenum

   Oslo University Hospital

   Affiliation as printed

   Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway

3. Mário A. P. Vaz

   St.John's Medical College Hospital

   Affiliation as printed

   Department of Physiology, St. John's Medical College and Division of Health and Humanities, St. John's Research Institute, Koramangala, Bangalore, India

4. Sumithra Selvam
   Affiliation as printed

   Division of Infectious Diseases, St. John's Research Institute, Koramangala, Bangalore, India

5. Tom H. M. Ottenhoff Aachen Department of Infectious Diseases Group

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Infectious Diseases Group, Immunology and Immunogenetics of Bacterial Infectious Disease, Leiden University Medical Center, Leiden, the Netherlands

6. Mariëlle C. Haks Aachen Department of Infectious Diseases Group

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Infectious Diseases Group, Immunology and Immunogenetics of Bacterial Infectious Disease, Leiden University Medical Center, Leiden, the Netherlands

7. Stephanus T. Malherbe

   South African Medical Research Council · Stellenbosch University

   Affiliation as printed

   DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

8. Mark T. Doherty

   GlaxoSmithKline (Belgium)

   Affiliation as printed

   GlaxoSmithKline Vaccines, Wavre, Belgium

9. Christian Ritz corresponding

   University of Copenhagen

   Affiliation as printed

   Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark. ritz@nexs.ku.dk

   Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark

10. Harleen M. S. Grewal

    Haukeland University Hospital · University of Bergen

    Affiliation as printed

    Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway

    Department of Microbiology, Haukeland University Hospital, University of Bergen, Bergen, Norway