Shingai Machingaidze, Suzanne Verver, Humphrey Mulenga, Deborah-Ann Abrahams, Mark Hatherill, Willem Hanekom, Gregory D. Hussey, and Hassan Mahomed Am J Respir Crit Care Med Vol 186, pp 1051–1056, Nov 15, 2012 R1 김민제 1 Predictive Value of Recent QuantiFERON Conversion for Tuberculosis Disease in Adolescents

Background  IGRAs (IFN-g release assays)  A new tool for the diagnosis of latent tuberculosis (TB) infection  Detection of INF- g released by T cells (after exposure of mononuclear cells to M. tuberculosis)  Fetures  Unaffected by prior BCG vaccination  Ex vivo assays (Require one visit)  Able to be repeated without sensitization or boosting  Standardized interpretation  IGRAs have been recommended for serial testing for TB infection in populations with continued risk of TB exposures 2

Background  Recent TST (Tuberculin Skin Test) conversion (risk of developing active TB disease)  However, recent IGRA conversion remains unknown  What is an IGRA “Conversion”  What is the “Prognosis” of IGRA conversion  What is an IGRA “Reversion”  Evidence is still required to answer key questions 3

Objective  The incidence rate of active TB disease after recent QuantiFERON Gold In-Tube (QFT) conversion in adolescents compared with those who did not convert  Assess “Predictive value of QTF conversion for active TB disease”  Assess “Effect of varying the definition of QFT conversion on the TB incidence rate” 4

Methods 5  Extension of ACS*  Prospective epidemiological cohort study of TB disease in 12 to 18 yrs of age  Followed for at least 2yrs From “July 2005” untill “February 2009”  QFT tests were scheduled for all participants at baseline and at 2 yr follow-up  “QFT nonconverters” : Remained QFT negative  “QFT converters” : Negative at baseline  Positive at 2yr follow-up visit  Selected participants underwent further period of observation for incident TB disease from March 2009 until September 2010 * ACS : Adolescent Cohort Study

TB Diagnosis and processes 6  All suspected participants were investigated through  Sputum smears cultures  Chest X-rays  Protocol defined case of TB : confirmed by two or more sputum smears (+) and/or one culture (+) * Uncertainty Zone : regarding QFT conversion, values falling in thes zone might not be “True conversion” [ 0.20 ~ 0.50 UL/ml]  “Doubtful conversion”

RESULT 7

RESULT 8

RESULT 9  Tuberculosis incidence rate ratio : ‘8.54’ for all cases

RESULT 10

RESULT 11  Uncertainty Zone [ 0.20 ~ 0.50 UL/ml ] ‘Doubtfull conversion’ : 116/ 534 (21.7%), 4/ 15 (26.7%)  QTF Reversion [ baseline IFN-g > 0.35 IU/ml, follow-up, <0.35 IU/ml ] : 241/ 2613

CONCLUSION 12  Recent QFT conversion was indicative of an approximately eight fold higher risk of progression to TB disease (compared with nonconverters) in a cohort of adolescents in a high–TB burden population  The predictive value of recent QFT conversion for the development of active TB disease is 2.6% within approximately 2 years after QFT conversion  Varying the definition of QFT conversion seems to have had minimal effect on the TB incidence rate in the QFT converter group

Comments 13  IPT(Isoniazid preventive therapy) for 100 adolescents, two or three subsequent TB cases would be averted  “Uncertainty Zone” showed 78% of QFT convertsions to be “true conversion”  A number of converters had less than 2 yrs follow up periods, and not all tests were available  The results of this study will strengthen the evidence base for IGRA guidelines,. However, a proper cost effectiveness analysis is needed to validate the use of these findings in low- and middle-income countries.