First Author (Reference) | Year | Study setting | Study population | Sample size | Study objective | Screening tool used | Comparator tool | Comparative screening results (SP, SE, discordance) | Findings/Recommendations regarding screening tools |
---|---|---|---|---|---|---|---|---|---|
Indigenous Communities | |||||||||
 Alvarez [25] | 2014 | Nunavut, Canada | A high-risk Indigenous community in Iqaluit, Nunavut | 256 (with both TST and IGRA results) | To evaluate the feasibility of the use of IGRAs for LTBI screening in the Nunavut Indigenous population | IGRA | TST | 44/256 (17.2%) discordant results, most of which occurred in people with multiple BCG vaccinations or those who were vaccinated after infancy | • 18% IGRAs positive, 32% TSTs positive. • IGRAs are a valid screening tool for LTBI in Nunavut, as most of the community is BCG-vaccinated, making IGRAs more specific. |
 Kwong [26] | 2016 | Sioux Lookout, Ontario, Canada | Indigenous adolescents in northern Ontario (screened at age 14) | 11 | To evaluate the IGRA for LTBI screening in a Canadian Indigenous community | IGRA | TST | 7/11 had a positive TST, of these 7, all had a negative IGRA and none developed symptoms of active TB disease. | • Recommends use of IGRAsv due to high proportion of false-positive TST in BCG vaccinated adolescents. |
 Reid [27] | 2007 | Saskatchewan, Canada | Preschool children (0–4 yrs) living in Indigenous reserve communities in Saskatchewan | 2953 (1086 BCG+, 1867 BCG-) | To investigate the effect of BCG vaccination on TST results in Canadian Indigenous children | TST | None |  | • More positive TSTs among BCG+ children at 5 mm for 0–4 yrs., but no longer significant in 3–4 yrs. at > 10 mm • Need to take BCG vaccination status and age into consideration when using TST to screen for LTBI in Indigenous communities |
Immigrant or refugee children | |||||||||
 Howley [41] | 2015 | USA | Children (2–14 yrs) immigrating to the US from Vietnam, the Philippines or Mexico | 2520 | To evaluate the QFT vs TST for LTBI screening in immigrant children | QFT | TST | • kappa = 0.20. QFT displayed stronger association with presence of risk factors for LTBI | • Recommends the use of QFT in immigrant children (2 yrs. and above) |
 Losi [42] | 2011 | Modena, Italy | Immigrant children and adolescents | 621 | To evaluate the QFT-GIT as a screening tool for LTBI in children immigrating to Italy | IGRA (QFT-GIT) | TST | • 104/621 TST+ • 80/621 QFT+ • 50 TST+/QFT+, • 30 TST inconcl./QFT+ 4 active TB cases suspected, all QFT-GIT+/TST+ | • QFTs useful for screening in low-burden settings, however, due to continued lack of research regarding sensitivity of IGRAs in younger children, TST positivity should not be disregarded |
 Lucas [43] | 2010 | Perth, Australia | African and Burmese refugee children resettling in Australia | 524 | To evaluate the QFT-GIT and T-SPOT.TB as screening tools for LTBI in refugee children resettling to Australia | QFT-GIT and TB-SPOT.TB | TST | • QFT-GIT and TB-SPOT.TB showed high concordance (k = 0.78, p < 0.0001). • Both had poor concordance with TST: 50%. • High failure rates (14 and 15% respectively) of T-SPOT and QFT-GIT | • High proportion of inconclusive results for both IGRAs suggests TST remains useful alternative. |
 Salinas [47] | 2015 | Spain | Undocumented immigrant children (< 19 yrs) in Basque Country, Spain | 845 | To determine the prevalence of LTBI in undocumented immigrant teenagers using QFT | QFT-GIT | TST | 63% overall, 57% positive and 96% negative concordance. | • Screening high-risk subgroups of the population in low-incidence countries is recommended. • The use of QFT as opposed to TST in this group reduced the provision of preventive treatment by 43% |
Children considered at risk based on suspected TB exposure/contact with a TB case (among other risk factors, including immigration or adoption) | |||||||||
 Bergamini [56] | 2009 | Italy | At-risk children (contacts of TB cases and recent immigrants) (0–19 yrs) | 496 | To investigate the effect of age on IGRA effectiveness | IGRAs (QFT-GIT, QFT-G, T-SPOT.TB) | None | • TST: uncertainty of accuracy in BCG-vaccinated children. QFTs: more indeterminate results in those < 4 yrs. compared to older children • T-SPOT: lower proportion of indeterminate results compared to QFTs | Need to take into account age and BCG vaccination status when using the TST for LTBI screening |
 Connell [38] | 2006 | Melbourne, Australia | High-risk children (suspected contact with an active case, recent arrival from high-incidence country, clinical suspicion) | 106 | To evaluate the effectiveness of LTBI screening with IFN-y vs. TST | IFN-γ assay | TST | • IFN-/TST+ in 70% of TST+ cases • Kappa = 0.3 | TST recommended for screening among high-risk children, as TST positivity was a better predictor of the possibility of actual LTBI (those with household contacts with TB were more likely to be positive by TST than by IFN-γ assay, although this does not necessarily translate into better predictiveness of the TST given that not all household contacts will necessarily develop LTBI). |
 Grare [39] | 2010 | Nancy, France | Children considered at risk for TB due to clinical suspicion, an adult case contact or recent immigration from an endemic region (< 18 yrs) | 51 (44 with test results) | To evaluate the effectiveness of QFT-GIT vs. the TST for the identification of paediatric LTBI | QFT-GIT | TST | 84% agreement between the two tests | • TST remains a useful predictor of LTBI. • High levels of inconclusive IGRA results suggest more studies are needed to determine its increased effectiveness vs. TST |
 Sali [45] | 2015 | Italy | Children (0–14 yrs) with suspected active TB, exposure to an adult case, or healthy adopted children | 621 | To evaluate the QFT-GIT for paediatric active TB diagnosis and LTBI screening | QFT-GIT | None |  | • Usefulness of IGRAs in younger children: 0–12 month age group more likely to have indeterminate QFT results (p = 0.001). • Children < 8 months: impaired ability to respond to mitogen compared to those > 8 months (but not statistically significant) |
 Salinas [46] | 2011 | Spain | Children < 17 yrs. in Basque Country, Spain, that had previous TB contacts | 160 | To compare the QuantiFERON-TB gold in-tube test to the TST for the detection of LTBI in children with TB contacts | QFT-GIT | TST | 95–96% concordance (100% in non-vaccinated children and children < 5 yrs) | • QFT-GT reduced preventive treatments by 28–34% and is therefore recommended in low-incidence countries |
Other Paediatric Populations | |||||||||
 Grinsdale [40] | 2016 | San Francisco, USA | Children < 15 yrs. screened for TB at 20 community clinics in San Francisco | 1092 | To assess the concordance of QFTs and the TST in a low-burden setting | QFT-GIT | TST | • 79% discordance (TST+/IGRA-) in BCG-vaccinated foreign-born children vs. 37% discordance in non-vaccinated US-born children. • Children > 5 yrs. also significantly more likely to have discordant results | • QFT vs. TST discordance was high, however, QFT has high NPV, as no TST+/QFT- children developed active TB disease in the 5 years of follow-up. • QFT may be a better predictor of risk of progression to active disease in low-burden setting |
 Mekaini [44] | 2014 | Abu Dhabi, UAE | Children (1–19 yrs) attending health centres in Abu Dhabi for routine care | 699 (669 gave blood sampling consent) | To evaluate the QFT-GIT for paediatric LTBI screening | QFT-GIT | Risk factor questionnaire | • QFT positivity was low (4/669, 0.6%), however it identified two LTBI cases that would have been suspected negative based on the risk factor questionnaire alone | QFT is recommended, depending on the estimated prevalence of TB in the population |
 Rose [29] | 2014 | Toronto, Canada | Paediatric HIV patients (< 19 yrs) | 81 | To evaluate the QFT-GIT for LTBI screening in HIV-positive children | QFT-GIT | TST | 96% TST-/QFT- concordance, but TST+/QFT+ concordance was low. | Use of QFT in HIV-positive children is valid, although low correlation with risk factor assessment (5 mm cut off used for the TST) |