title: Cytokine Kinetics in the First Week of Tuberculosis Therapy as a Tool to Confirm a Clinical Diagnosis and Guide Therapy.
abstract: BACKGROUND
  Many patients treated for tuberculosis (TB) in low and middle income countries are treated based on clinical suspicion without bacteriological confirmation. This is often due to lack of rapid simple accurate diagnostics and low healthcare provider confidence in the predictive value of current tests. We previously reported in an animal TB model that levels of host markers rapidly change in response to treatment initiation.
  
  
  METHODS
  We assessed the potential of host biomarker kinetics of TB patients during the first two weeks of therapy to identify patients responding to treatment. Adult patients clinically diagnosed with and treated for TB, 29 in Nigeria and 24 in Nepal, were analyzed.
  
  
  RESULTS
  Changes in concentrations of non-specific host biomarkers, particularly IP-10, in response to the first week of anti-TB therapy were strongly associated with bacteriological confirmation of TB. A decrease in IP-10 level of >300pg/ml between 0 and 7 days of treatment identified 75% of both smear-positive and smear-negative culture positive patients and correctly excluded TB in all nine culture negative patients.
  
  
  CONCLUSIONS
  Monitoring of early IP-10 responses to treatment could form the basis of a simplified assay and could help identify patients who were erroneously clinically diagnosed with TB or those infected with drug resistant strains on inappropriate treatment. We believe this approach may be particularly appropriate for difficult to diagnose patients, e.g. smear-negative HIV-positive, or those with extra-pulmonary TB, often treated without bacterial confirmation.
authors.affiliation: Royal Tropical Institute (KIT), KIT Biomedical Research, Amsterdam, The Netherlands.
authors.forename: Alice L
authors.initials: AL
authors.lastname: den Hertog
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: María
authors.initials: M
authors.lastname: Montero-Martín
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Saunders
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Blakiston
authors.affiliation: Royal Tropical Institute (KIT), KIT Biomedical Research, Amsterdam, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Menting
authors.affiliation: Tribhuvan University Institute of Medicine, Kathmandu, Nepal.
authors.forename: Jeevan B
authors.initials: JB
authors.lastname: Sherchand
authors.affiliation: Zankli Medical Centre, Abuja, Nigeria.
authors.forename: Lovett
authors.initials: L
authors.lastname: Lawson
authors.affiliation: Zankli Medical Centre, Abuja, Nigeria.
authors.forename: Olanrewaju
authors.initials: O
authors.lastname: Oladimeji
authors.affiliation: Abuja Federal Capital Territory Tuberculosis Control Programme, Abuja, Nigeria.
authors.forename: Saddiq T
authors.initials: ST
authors.lastname: Abdurrahman
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Cuevas
authors.affiliation: Royal Tropical Institute (KIT), KIT Biomedical Research, Amsterdam, The Netherlands.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Anthony
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers; D054357:Chemokine CXCL10 / Q000097:blood; D060085:Coinfection; D016207:Cytokines / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006679:HIV Seropositivity; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001323:Autoantibodies; D015415:Biomarkers; D054357:Chemokine CXCL10; D016207:Cytokines