A prospective large-scale study of methods for the detection of latent Mycobacterium tuberculosis infection in refugee children
- Michaela Lucas1,
- Pam Nicol2,
- Elizabeth McKinnon3,
- Rebecca Whidborne1,
- Andrew Lucas3,
- Aesen Thambiran4,
- David Burgner5,
- Justin Waring6,
- Martyn French7
- 1Department of Clinical Immunology, Royal Perth Hospital and Pathwest Laboratory Medicine, Perth, Western Australia
- 2School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia
- 3Centre for Clinical Immunology and Biomedical Statistics, Murdoch University, Perth, Western Australia
- 4Migrant Health Unit, North Metropolitan Area Health Service, Perth, Western Australia
- 5Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria
- 6TB Control Program, North Metropolitan Area Health Service, Perth, Western Australia
- 7School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia
- Correspondence to Dr Michaela Lucas, Department of Clinical Immunology, Royal Perth Hospital, GPO Box X2213, Perth WA 6847, Australia;
Contributors The study was conceived by ML, JW and DB, designed by ML, DB, JW, EM and MF, and overseen by MF. Clinical data were collected by PN and AT and laboratory assays conducted by RW. All authors contributed to data interpretation, with statistical analysis undertaken by EM. ML, PN, EM, AL, DB and MF made key contributions to early drafts of the manuscript, with all authors involved in its critical review and providing final approval.
- Received 24 September 2009
- Accepted 18 February 2010
Background Diagnosis of latent tuberculosis infection (LTBI) is a cornerstone of the health assessment of resettled high incidence populations, particularly in children. Two blood-based interferon γ release assays (IGRAs), T-SPOT.TB and QFT-Gold in-tube (QFT-GIT), have greater sensitivity and specificity than the tuberculin skin test (TST), but their performance as screening tools for LTBI in children, especially refugee children, remains unclear.
Methods 524 African and ethnic Burmese children, including 107 under 3 years of age, were prospectively enrolled in a comparison of the T-SPOT.TB and QFT-GIT. The TST was also performed in 342 of the children.
Results The T-SPOT.TB and QFT-GIT had similar rates of positivity (8% and 10%, respectively) and showed good concordance when both tests gave definitive results (κ=0.78; p<0.0001). However, the IGRAs had significant failure rates: 15% of QFT-GIT gave indeterminate results due to failed mitogen response and 14% of T-SPOT.TB results were inconclusive, largely because of insufficient mononuclear leucocyte yields. Failure of the QFT-GIT mitogen response was associated with African ethnicity and co-morbid infections, particularly with helminths. The TST results showed poor concordance (∼50%) with both IGRAs.
Conclusions It is reasonable to screen using either IGRA with follow-up by the alternative if the test fails. In general, the QFT-GIT is the preferred option for non-African populations but the T-SPOT.TB is recommended when there are epidemiological and/or clinical high risk factors for TB infection. However, both IGRAs have methodological and performance characteristics that limit their usefulness in refugee children, highlighting the need for continued development of screening strategies.
- Immunodiagnostics for tuberculosis
- interferon gamma release assays
- latent tuberculosis infection
- migrant/refugee screening
- paediatric health
- paediatric lung disaese
- respiratory infection
Funding The research described in this manuscript has been funded by Oxford Immunotech. Oxford Immunotech was not involved in the planning or implementation of the study nor the interpretation of the data.
Competing interests None.
Ethics approval This study was approved by the Royal Perth Hospital Ethics Committee (EC 2007/014).
Provenance and peer review Not commissioned; externally peer reviewed.