Dataset Information

Longitudinal analysis of QuantiFERON-TB Gold In-Tube in children with adult household tuberculosis contact in South Africa: a prospective cohort study.

ABSTRACT:

Background

QuantiFERON-TB Gold In Tube (QFT-GIT) is a tool for detecting M. tuberculosis infection. However, interpretation and utility of serial QFT-GIT testing of pediatric tuberculosis (TB) contacts is not well understood. We compared TB prevalence between baseline and 6 months follow-up using QFT-GIT and tuberculin skin testing (TST) in children who were household contacts of adults with pulmonary TB in South Africa, and explored factors associated with QFT-GIT conversions and reversions.

Method

Prospective study with six month longitudinal follow-up.

Results

Among 270 enrolled pediatric contacts, 196 (73%) underwent 6-month follow-up testing. The 6-month prevalence estimate of MTB infection in pediatric contacts increased significantly from a baseline of 29% (79/270, 95%CI [24-35]) to 38% (103/270, 95% CI [32-44], p<0.001) using QFT-GIT; prevalence increased from a baseline of 28% (71/254, 95%CI [23-34]) to 33% (88/263, 95%CI [21-32], p = 0.002) using TST. Prevalence estimates were influenced by thresholds for positivity for TST, but not for QFT-GIT. Among 134 children with a negative or indeterminate baseline QFT-GIT, 24 (18%) converted to positive at follow-up; conversion rates did not differ significantly when using more stringent thresholds to define QFT-GIT conversion. Older age >10 years (AOR 8.9 95%CI [1.1-72]) and baseline TST positivity ≥5 mm (AOR 5.2 95%CI [1.2-23]) were associated with QFT-GIT conversion. Among 62 children with a positive baseline QFT-GIT, 9 (15%) reverted to negative; female gender (AOR 18.5 95%CI [1.1-321]; p = 0.04] was associated with reversion, while children with baseline positive TST were less likely to have QFT-GIT reversion (AOR 0.01 95%CI [0.001-0.24]).

Conclusion

Among pediatric contacts of adult household TB cases in South Africa, prevalence estimates of TB infection increased significantly from baseline to 6 months. Conversions and reversions occurred among pediatric TB contacts using QFT-GIT, but QFT-GIT conversion rates were less influenced by thresholds used for conversions than were TST conversion rates.

SUBMITTER: Shah M

PROVIDER: S-EPMC3204993 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe QuantiFERON®-TB Gold In-Tube test (QFT-GIT) is a viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. However, within-subject variability may limit test utility. To assess variability, we compared results from the same subjects when QFT-GIT enzyme-linked immunosorbent assays (ELISAs) were performed in different laboratories.MethodsSubjects were recruited at two sites and blood was tested in three labs. Two labs used the same type of automated ELISA workstation, 8-point calibration curves, and electronic data transfer. The third lab used a different automated ELISA workstation, 4-point calibration curves, and manual data entry. Variability was assessed by interpretation agreement and comparison of interferon-? (IFN-?) measurements. Data for subjects with discordant interpretations or discrepancies in TB Response >0.05 IU/mL were verified or corrected, and variability was reassessed using a reconciled dataset.ResultsNinety-seven subjects had results from three labs. Eleven (11.3%) had discordant interpretations and 72 (74.2%) had discrepancies >0.05 IU/mL using unreconciled results. After correction of manual data entry errors for 9 subjects, and exclusion of 6 subjects due to methodological errors, 7 (7.7%) subjects were discordant. Of these, 6 (85.7%) had all TB Responses within 0.25 IU/mL of the manufacturer's recommended cutoff. Non-uniform error of measurement was observed, with greater variation in higher IFN-? measurements. Within-subject standard deviation for TB Response was as high as 0.16 IU/mL, and limits of agreement ranged from -0.46 to 0.43 IU/mL for subjects with mean TB Response within 0.25 IU/mL of the cutoff.ConclusionGreater interlaboratory variability was associated with manual data entry and higher IFN-? measurements. Manual data entry should be avoided. Because variability in measuring TB Response may affect interpretation, especially near the cutoff, consideration should be given to developing a range of values near the cutoff to be interpreted as "borderline," rather than negative or positive.

Project description:BackgroundQuantiFERON-TB Gold In-Tube® (QFT-GIT) test is used for the diagnosis of latent tuberculosis (TB) infection. Besides, QFT-GIT test could allow tracking changes in immune response among TB patients and their contacts. In high TB burden settings, reports on QFT-GIT conversions and reversions among TB patients and their contacts are limited. As part of a major project to study immune responses to TB infection, we investigated QFT-GIT test conversions and reversions among smear positive pulmonary TB patients and their household contacts over 12 months.MethodsWe followed a total of 107 HIV negative participants (33 patients and 74 contacts) in Addis Ababa. We did QFT-GIT test at baseline and 12 months later according to the manufacturer's instructions.ResultsAt baseline, 25/33 (75.8%) of the patients and 50/74 (67.6%) of the contacts were QFT-GIT positive. At 12 months, 2 more patients (1 test negative and 1 indeterminate) became test positive. Besides, 11/24 (45.8%) test negative contacts became positive. Only one patient and one contact who were test positive at baseline became test negative 12 months later. At 12 months, the proportions of QFT-GIT test positives for patients and contacts were, therefore, 78.8% and 81.1%, respectively. Among contacts, the proportion of QFT-GIT test positives at 12 months was significantly higher compared to the corresponding proportion at baseline (McNemar, p?=?0.006); similarly, the median IFN-? response significantly increased at 12 months compared with the baseline level (Wilcoxon matched-pairs signed rank test, p?=?0.01). Patients, however, had comparable median IFN-? levels at baseline and 12 months later (p?=?0.56).ConclusionNearly half of QFT-GIT negative household contacts at baseline became positive at 12 months. This suggests that repeated screening of QFT-GIT negative contacts may be needed for epidemiological studies and interventions of latent TB in an endemic setting. A large longitudinal study may be needed to confirm our observations.

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