Skip to main content

Table 2 Studies investigating the feasibility and performance of screening tools for paediatric LTBI (by study population)

From: Recommendations for the screening of paediatric latent tuberculosis infection in indigenous communities: a systematic review of screening strategies among high-risk groups in low-incidence countries

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)