Table 1.
Household contact study | Study location | Risk score used | Tests used | Cut-offs | Resister’ definition | Other definitions | LTBI definition |
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Stein et al. (11, 12) | Kampala, Uganda | Validated TB risk score by Mandalakas et al. (13); Ma et al. (14) | TST (5 tuberculin units [TU], PPD-S2, Tubersol, Sanofi Pasteur Limited, USA) QFT Gold In-Tube (QFT-GIT) |
TST: 10mm (HIV− contacts) and 5mm (HIV+ contacts) QFT: IFN-γ (TB Ag – Nil) at 0.35 IU/ml |
Initial houlsehold contact study: TST negative after at least 12 months of follow-up. Retracing study: Three negative QFT tests (one at baseline and two others during the 1-2 year follow-up period) and a final negative TST following the last QFT test. Average duration of time in between studies: 9.5 years. |
Probable ’resister’: one ‘low level positive’ QFT that disagreed with the other 4 data points. A low level positive included values of 0.35 IU/ml < IFN-γ (TB Ag – Nil) < 0.5 IU/ml. Possible ’resister’: TST induration ≤ 8mm or one QFT positive plus all other negative tests or a TST negative incomplete with 2 negative QFTs but missing the last visit of the study. |
Definite LTBI: All TST and QFT +. Definite converters: Persistently TST negative in initial study who converted to 3+ QFT and a +TST on retracing. |
Mave et al. (15) | Chennai and Pune, India | Validated TB risk score by Mandalakas et al. (13); Ma et al. (14) | TST (5 TU, PPD, SPAN/Arkray, India) QFT-GIT |
TST: 5mm QFT: IFN-γ (TB Ag – Nil) at 0.35 IU/ml |
HHCs with high TB exposure who were TST and QFT negative at baseline and up to 12 months following exposure (TST < 5mm and QFT IFN-γ (TB Ag – Nil) < 0.35 IU/mL). |
Persistent LTBI negative (pLTBI-): TST and QFT negative at baseline and up to 12 months following exposure. ’Resisters’ with complete absence of response: TST = 0mm and IFN-γ (TB Ag – Nil) < 0.01 IU/ml. |
LTBI: At least one positive TST or QFT test. TST ≥ 5mm or QFT IFN-γ (TB Ag – Nil) ≥ 0.35 IU/mL. |
Verrall et al. (16, 17) | Bandung, Indonesia | Score, derived using regression methods, was based on the index TB case’s sputum smear grade, the presence of cavities and the extent of the CXR disease | QFT- GIT | IFN-γ (TB Ag – Nil) at 0.35 IU/ml | Persistently negative (Early clearers): Persistently IFN-γ (TB Ag – Nil) < 0.35 IU/ml at baseline and at 14 weeks. | Conversion: IFN-γ (TB Ag – Nil) < 0.35 IU/ml at baseline to IFN-γ (TB Ag – Nil) > 0.35 IU/ml at 14 weeks. | |
Hill et al. (18) | Banjul, The Gambia | No risk score used | TST (2 TU, PPD RT23, Statens Serum Institut, Denmark) ELISPOT |
TST: 10mm ELISPOT: For a positive ESAT-6/CFP-10 result it was necessary for at least one of the two pools of overlapping peptides to be positive. Phytohaemagglutinin wells were set to at least 150 SFU/well/2 x 10^5 above negative control wells. Negative control wells were required to have less than 20 SFU. |
HHCs with high TB exposure: TST < 5mm at baseline and 18 months following exposure and negative ELISPOT at baseline, 3 months and 18 months following exposure. |
TST conversion: Negative at baseline and ≥ 10 mm & an increase in induration ≥ 6 mm at 18 months. Positive ELISPOT: ESAT-6/CFP-10- at least one of the two pools of overlapping peptides positive. ELISPOT conversion: as a newly positive test, plus a change in the combined ESAT-6 and CFP-10 count (> negative control) ≥ 6 SFU/well/2x10^5 (30 SFU/million cells). |
|
Coulter et al. (19) | The Gambia | Based on sleeping proximity to the index TB case and smear grade of the index TB case | in-house IGRA | Unknown | Non-converters: IGRA negative at baseline and at 6 months |
LTBI: IGRA positive at baseline IGRA converters: IGRA negative at baseline and IGRA positive at 6 months |
|
Medawar et al. (20) | The Gambia | HHCs sleeping in the same room as index TB case | QFT-GIT | Negative QFT: IFN-γ (TB Ag – Nil) ≤ 0.2 Positive QFT: IFN-γ (TB Ag – Nil) ≥ 0.7 |
QFT nonconverters: IGRA negative at baseline and at 6 months | QFT reverters: IGRA positive at baseline and IGRA negative at 6 months |
LTBI: IGRA positive at baseline and at 6 months IGRA converters: IGRA negative at baseline and IGRA positive at 6 months |
Weiner et al. (21) | The Gambia | Based on sleeping proximity to the index TB case and smear grade of the index TB case |
Cohort 1: TST (2 TU, PPD RT23, Statens Serum Institut, Denmark) Cohort 2: QFT-GIT |
TST: 10mm QFT: IFN-γ (TB Ag – Nil) at 0.35 IU/ml |
Cohort 1
TST nonconverters: TST = 0mm at baseline and at 3 months. Cohort 2 Nonconverters: IFN-γ (TB Ag – Nil) < 0.35 IU/mL at baseline and at 6 months. |
Cohort 1: (TST converters) 0 mm at baseline and converted to positive >10 mm by 3 months. Cohort 2: (converters) IFN-γ (TB Ag – Nil) < 0.35 IU/mL at baseline and IFN-γ (TB Ag – Nil) > 0.35 IU/mL at 6 months. | |
Aissa et al. (22) and Cobat et al. (23) | Val de Merne, Paris, France | Exposure measures included daytime and nighttime proximity to the index case, duration of exposure to the index case in number of days during the 3 months prior to the index case’s diagnosis, and the index case infectivity. Index case infectivity was assessed using the duration of cough before diagnosis, presence of cavitation and extent of disease on CXR, and bacillary density in sputum smears and culture | TST (2 TU, PPD RT23, Statens Serum Institut, Denmark) | Aissa et al.: 5mm Cobat et al.: 0mm |
Aissa et al.: TST < 5mm at baseline (V1) and 8-12 weeks (V2) Cobat et al.: TST = 0mm at V2 and V2 |
LTBI: TST ≥ 10 mm (no prior BCG vaccination). TST ≥ 15 mm at V1 or V2 or converted from TST < 5mm (V1) to TST ≥ 10 mm at V2 (BCG-vaccinated contacts). | |
Quistrebert et al. (24) | Southern Vietnam | No risk score used |
Vienam cohort: TST (5 TU, Tubertest, Sanofi Pasteur, France) and QFT-GIT Val de Merne cohort: in-house IGRA South African cohort: in-house IGRA |
TST: 5mm QFT: IFN-γ (TB Ag – Nil) at 0.35 IU/ml |
Vietnam cohort
Double negatives: TST < 5mm and QFT-GIT IFN-γ (TB Ag – Nil) < 0.35 IU/mL Val de Merne cohort (Aissa et al.) Negative: (i) TST < 5 mm at both V1 and V2, ii) < 5 mm at V1, when only one visit was done Uninfected subjects: HHCs with a negative TST and a null IFN-γ production South African cohort Uninfected: TST < 5 mm and a null IFN-γ production |
Vietnam study
Double positives: TST ≥ 5mm and a positive QFT-GIT IFN-γ (TB Ag – Nil) ≥ 0.35 IU/mL. French study Positive: TST i) ≥ 5 mm at both V1 and V2, ii) < 5 mm at V1 and ≥ 10 mm at V2. Infected subjects as HHCs who presented both a positive TST and a positive IGRA result (IFN-γ production > 175 pg/mL) South African cohort Infected: Both positive TST and IGRA result (IFN-γ production > 20.9 pg/mL). |
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Chen et al. (25) | Shanghai, China | Based on shared air space with an individual with pulmonary TB in the household or other indoor setting for > 15 hr per week or > 180 hr total during an infectious period (an infectious period was defined as the interval from 3 months before collection of the first culture-positive sputum specimen or the date of onset of cough, whichever was longer, through 2 weeks after the initiation of appropriate anti-tuberculosis treatment) | ELISPOT (TS-SPOT; Beijing Jinhao, China) | Positive if either Panel Test (containing ESAT-6/CFP-10/Rv3615c peptides pool) showed at least six spot-forming cells (SFCs) more than the negative control when the negative control ≤5 SFCs; or if the number of spots in Panel Test was at least double the number in the negative control when the negative control >5 SFCs | Resisters: persons who were highly exposed to Mtb and were IGRA/TST negative without clinical syndromes of active TB infection at enrollment. However, no TST was performed | LTBI: persons who were highly exposed to Mtb and were IGRA/TST positive without clinical syndromes of active TB infection at enrollment. However, no TST was performed | |
Vorkas et al. (26) | Port-au-Prince, Haiti | Based on living in the same house as the active TB case for at least 1 month in the 6 months prior to diagnosis | QFT-GIT | Not specified | HHCs with IGRA negative result at enrollment | HHCs with IGRA positive result at enrollment |