Determining Mycobacterium tuberculosis infection among BCG-immunised Ugandan children by T-SPOT.TB and tuberculin skin testing.
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.


RESULTS
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
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.
Co-infection Studies Programme, Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe, Uganda. gyaviira.nkurunungi@mrcuganda.org
Gyaviira
G
Nkurunungi
Jimreeves E
JE
Lutangira
Swaib A
SA
Lule
Hellen
H
Akurut
Robert
R
Kizindo
Joseph R
JR
Fitchett
Dennison
D
Kizito
Ismail
I
Sebina
Lawrence
L
Muhangi
Emily L
EL
Webb
Stephen
S
Cose
Alison M
AM
Elliott
D001500:BCG Vaccine / Q000009:adverse effects / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D014373:Tuberculin / Q000276:immunology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D014454:Uganda
D001500:BCG Vaccine; D014373:Tuberculin