Predictive values of IGRAs and TST for progression to active disease in TB. 3 rd Global IGRA Symposium January 2012.

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1 Predictive values of IGRAs and for progression to active disease in TB contacts in Singapore Cynthia B E Chee 1, K W KhinMar 1, S H Gan 1, J Cutter, T M Barkham, Y T Wang 1 1 TB Control Unit, Tan Tock Seng Hospital, Singapore Communicable Disease Division, Ministry of Health, Singapore Dept of Laboratory Medicine, Tan Tock Seng Hospital, Singapore rd Global IGRA Symposium 1-15 January 1 Background Singapore: an intermediate TB incidence country Since 195s : universal BCG-vaccination at birth 195s - 1 : BCG re-vaccination policy for school leavers (at 1 or 16 years of age) : Stagnation of TB rate at 5-55 /1, population (citizens/permanent residents) 1998: National TB Programme implemented targeted screening of close contacts for preventive therapy () 4: Availability of commercial IGRAs

2 Two cohorts of adult non-hiv contacts tested with an IGRA and (TU RT PPD) 961 community contacts (household, workplace) Screened with T-SPOT.TB and from January-September 5; Decision for based on T-SPOT result in the majority regimen: Isoniazid for 6 months, self-administered 11 contacts in congregate settings (prisons, nursing homes, mental institute) Screened with QuantiFERON Gold In-tube (QFT-IT) and from November 5-May 7 Decision for based on QFT result regimen: Isoniazid for 9 months, directly-observed Of eligible contacts, 81% in T-SPOT cohort; 85% in QFT cohort commenced Completion rate : 77% for T-SPOT cohort; 89% for QFT cohort Follow-up: commenced on were followed 4-6 weekly until treatment completion, then discharged QFT +ve contacts in congregate settings who could not take were reviewed 6 monthly for years Test-positive community contacts who did not take were discharged with advice Test-negative contacts were discharged matched with National TB Notification Registry for notification of active TB as at July (6 in T-SPOT group, 1 in QFT group) One case with known re-exposure to active TB excluded (T-SPOT group)

3 screened with T-SPOT and Flow-chart according to T-SPOT 961 of 99 T-SPOT +ve # 98 (44%) T-SPOT ve 55 (56%) 64 No * % 6 active TB 1 failed T-SPOT 51 without either test result # >= 6 SFCs /5, PBMCs No * 477 * Includes non-completers 99.6% screened with T-SPOT and Flow-chart according to (1 mm cut-off) 961 of 99 >= 1 mm 77 (8%) < 1 mm 166 (18%) 8 No * % 6 active TB 1 failed T-SPOT 51 without or T-SPOT results No * 157 * Includes non-completers 1%

4 Number screened with both tests N=9 Treatment status No. who developed active TB / No. screened Person-years Incidence / 1 PYs T-SPOT-/- / N=141 (15.6%) No / T-SPOT-/+ / N=64 (4.%) No /7 (.9%) T-SPOT+/- / N=5 (.8%) No / T-SPOT+/+ /56 (.8%) N=7 (41.%) No 1/117 (.9%) positivity cutoff >=1 mm screened with QFT-IT and Flow-chart according to QFT 11 of 7 QFT +ve 75 (5%) QFT ve 814 (75%) 191 No * 84.% 1 Active 1 Indeterminate QFT 8 No No % * includes non-completers

5 screened with QFT-IT and Flow-chart according to (1 mm cut-off) 11 of 7 >= 1mm 645 (59%) < 1 mm 444 (41%) 155 No * Active 1 Indeterminate QFT 8 No No * 48 * Includes non-completers 99. Number screened with both tests N=189 Treatment status No. who developed active TB / No. screened QFT-/- / Personyears Incidence / 1 PYs N=97 (6.5%) No /97 (.8%) QFT-/+ / N=417 (8.%) No 4/417 (1.%) QFT+/- / N=47 (4.%) No /11.6 QFT+/+ /155 (1.9%) N=8 (.9%) No /7 (.7%).4 8. positivity cutoff >=1 mm

6 Limitations Majority of IGRA-positive subjects received LTBI treatment Possible selection bias for those who did not receive Rx (more HH than non-hh contacts received in T-SPOT group) No DNA fingerprinting data of contact and source MTC isolates Unable to rule out possibility of infection during follow-up period (5 developed active TB > 6 months after screening) No systematic follow-up of all contacts Drop out rate (eg. death, left country) uncertain Summary of findings of T-SPOT.TB :.7% (vs.7%) of T-SPOT.TB : 99.6% (vs 1%) T-SPOT+/+ contacts have RR of [95% CI ] of developing active TB vs those T-SPOT- /+ of QFT-IT :.% (vs 1.%) of QFT-IT : 99.1% (vs 99.%) QFT+/+ contacts have RR of 4.1 [95% CI.77-.] of developing active TB vs those QFT-/+; and RR of [95% CI ] of developing active TB vs those QFT-/-

7 Conclusions For TB contacts in Singapore s intermediate burden setting: Both T-SPOT and QFT-IT, and had low Consistent with meta-analysis by Rengaka et al. Lancet 1;1:45-55 All three tests had high In our population, use of IGRA will reduce number considered for Acknowledgements Nursing Officer Kwee-Yin Han, Senior Staff Nurses Pushparani and Chwee-Kim Koh & Staff of TB Control Unit Contact Clinic Mr Chua Sock Kiang and Staff, Singapore Prisons Service Dr Shen Liang, Yong Loo Lin School of Medicine, National University of Singapore Oxford Immunotec for providing T-SPOT.TB kits at a reduced price for this project Ministry of Health, Singapore