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Determining Mycobacterium tuberculosis infection among BCG-immunised Ugandan children by T-SPOT.TB and tuberculin
Gyaviira Nkurunungi1, Jimreeves E Lutangira, Swaib A Lule
1Co-infection Studies Programme, Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe, Uganda. gyaviira.nkurunungi@mrcuganda.org
Insights
Diagnosing latent tuberculosis infection (LTBI) in children is challenging. T-SPOT.TB test results were unstable over three weeks, and agreement with the tuberculin skin test was poor in Ugandan children.
Area of Science:
- Pediatric infectious diseases
- Immunology of tuberculosis
- Diagnostic test evaluation
Background:
- Latent tuberculosis infection (LTBI) in children is a significant public health concern, representing a reservoir for future disease.
- Limited data exist on the performance of immunoassays for diagnosing tuberculosis infection in children in endemic settings.
- BCG vaccination is common in endemic areas, potentially affecting test results.
Purpose of the Study:
- To determine Mycobacterium tuberculosis (M.tb) infection prevalence in BCG-immunised five-year-old children in Entebbe, Uganda.
- To evaluate the agreement between the T-SPOT.TB assay and the tuberculin skin test (TST).
- To assess the reproducibility of the T-SPOT.TB assay on short-term follow-up.
Main Methods:
- A cohort of 907 five-year-old children was recruited, including 56 household contacts of TB patients.
- Children were tested with T-SPOT.TB at baseline and re-tested approximately three weeks later.
- Tuberculin skin test (TST) was also administered at follow-up.
Main Results:
- At age five, 9.7% of children tested positive by T-SPOT.TB.
- Over half of T-SPOT.TB positive children at baseline were negative at follow-up; 96% of negatives remained negative.
- Agreement between T-SPOT.TB and TST was weak (κ=0.28-0.40), and T-SPOT.TB results showed instability over three weeks.
Conclusions:
- T-SPOT.TB positivity in children is unstable over a three-week interval.
- The TST shows poor agreement with T-SPOT.TB, complicating the diagnosis of TB infection in children.
- Current diagnostic tools for TB infection are unsatisfactory for children in this setting.
Background:
Children with latent tuberculosis infection (LTBI) represent a huge reservoir for future disease. We wished to determine Mycobacterium tuberculosis (M.tb) infection prevalence among BCG-immunised five-year-old children in Entebbe, Uganda, but there are limited data on the performance of immunoassays for diagnosis of tuberculosis infection in children in endemic settings. We therefore evaluated agreement between a commercial interferon gamma release assay (T-SPOT.TB) and the tuberculin skin test (TST; 2 units RT-23 tuberculin; positive defined as diameter ≥10 mm), along with the reproducibility of T-SPOT.TB on short-term follow-up, in this population.
Methodology/Principal Findings:
We recruited 907 children of which 56 were household contacts of TB patients. They were tested with T-SPOT.TB at age five years and then re-examined with T-SPOT.TB (n = 405) and TST (n = 319) approximately three weeks later. The principal outcome measures were T-SPOT.TB and TST positivity. At five years, 88 (9.7%) children tested positive by T-SPOT.TB. More than half of those that were T-SPOT.TB positive at five years were negative at follow-up, whereas 96% of baseline negatives were consistently negative. We observed somewhat better agreement between initial and follow-up T-SPOT.TB results among household TB contacts (κ = 0.77) than among non-contacts (κ = 0.39). Agreement between T-SPOT.TB and TST was weak (κ = 0.28 and κ = 0.40 for T-SPOT.TB at 5 years and follow-up, respectively). Of 28 children who were positive on both T-SPOT.TB tests, 14 (50%) had a negative TST. Analysis of spot counts showed high levels of instability in responses between baseline and follow-up, indicating variability in circulating numbers of T cells specific for certain M.tb antigens.
Conclusions/Significance:
We found that T-SPOT.TB positives are unstable over a three-week follow-up interval, and that TST compares poorly with T-SPOT.TB, making the categorisation of children as TB-infected or TB-uninfected difficult. Existing tools for the diagnosis of TB infection are unsatisfactory in determining infection among children in this setting.
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