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Serial IGRA testing of trainees in the healthcare sector in a country with low incidence for tuberculosis - a prospective cohort study.

ABSTRACT: BACKGROUND: Healthcare workers (HCW) are a risk group for tuberculosis (TB). That is why interferon-gamma release assay (IGRA) serial testing is performed on HCWs repeatedly exposed to infectious patients or materials. However, the variability of IGRA in serial testing is not yet well understood. We therefore analysed the prevalence of positive IGRA results as well as conversion and reversion rates in the serial testing of healthcare trainees in a low-incidence country. METHODS: In a prospective cohort study, all trainees (n=194) who began training as a nurse or healthcare worker at the Vivantes Healthcare Training Institute in Berlin on 1 October 2008 or 1 April 2009 were IGRA-tested at three different times during the three years of training. Socio-demographic data and possible risk factors (e.g., TB contacts, time spent abroad, area of work) were recorded by means of a standardised questionnaire. The QuantiFERON Gold In-Tube (QFT) was used as an IGRA. RESULTS: At the beginning of the training the cohort comprised 194 trainees. 70% were female. Their average age was 23. The prevalence of positive QFT was 2.1% (4/194). In the first follow-up test, 2 out of 154 (1.3%) tested IGRA-positive, 151 (98%) had constantly negative results. One IGRA was constantly positive (0.6%) and there was one conversion and one reversion (0.6% respectively). In the second follow-up (n=142) there was again one conversion (0.7%), one reversion and the one constantly positive test result in all three QFT. This trainee had active TB in 2002. All other test results were constantly negative (n=139; 98%). No case of active tuberculosis was diagnosed over the three-year observation period. Contact with TB patients was reported by 42 (29.6%) trainees during the follow-up. The two trainees with a conversion in QFT had no known contact with TB patients. Discordant results in the three consecutive QFT were observed in three trainees (2.1%). Using a borderline zone from 0.2-0.7 IU/mL reduced the number of trainees with discordant results from three to one - a reversion. CONCLUSION: The prevalence rate of latent TB infection is low in healthcare trainees without known risk factors for TB infection in their history. The infection risk seems to be low in this population even though contacts with TB patients during the training were reported. Introducing a borderline zone for the interpretation of reversions and conversions in this cohort appears to be safe and reduces the number of discordant results and helps to avoid unnecessary chest X-rays and preventive treatment.

SUBMITTER: Schablon A

PROVIDER: S-EPMC3857277 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Project description:Health care workers (HCW's) are always at an increased risk of contracting tuberculosis (TB) infection. In Saudi Arabia, Interferon Gamma Release Assay (IGRA) has not been evaluated as a screening tool for latent TB infection (LTBI) among HCW's considering their high demographic diversity. During February 2012 to January 2015 a cross sectional study has been conducted in a tertiary care center with maximum demographically diverse staff population in the capital city-Riyadh. After a short interview and consenting, all the candidates were subjected to tuberculin skin test (TST) and QuantiFERON TB gold In-tube test (QFT). A logistic regression analysis was carried out for establishing the associations between putative risk factors and the diagnostic tests. The candidates were classified according to geographical origin and a detailed analysis was conducted on the impact of their origin towards the results of TST and QFT. Of the 1595 candidates enrolled, 90.6% were BCG vaccinated, female (67.9%) and mainly nurses (53.2%). Candidates with high risk of suspected or confirmed TB patient exposure were 56.1% and 76.5% of them had <10 year's work experience. TST positivity was observed in 503 (31.5%) candidates, while QFT was positive among 399 (25%). Majority of the candidates were non-Saudi (83%) and predominantly (52.4%) from Western Pacific region. Concordant results were obtained in 14.2% of positive cases and 57.7% negative cases. The disagreements between the two tests were relatively high (kappa co-efficient-0.312±0.026, p value- <0.00001) as TST positive/QFT negative discordance was 54.8% while TST negative/QFT positive discordance was 15.7%. Age of the candidates, BCG vaccination, and South East Asian origin were associated with TST positivity while Occupational TB exposure and geographical origin of the candidates were associated with QFT positivity. A regular follow up on recently TST converted candidates showed no progression to active TB. The putative factors associated with the discordance were origin of the candidate (p value <0.001), profession (p value-0.001), BCG vaccination (p value-0.001) and occupational TB exposure level (P value-0.001). The study demonstrated high level prevalence of LTBI among the demographically diverse study candidates. The agreement between QFT and TST was poor, thus QFT alone cannot be recommended in our setting for a routine LTBI screening. Origin of the candidates has strong association with the results of TST and QFT. The discordant results particularly TST negative and QFT positive needs more detailed analysis.

Project description:Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. RESULTS:Between July 6, 2005, and April 23, 2007, we enrolled 6363 from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66Â·1% (95% CI 63Â·2â68Â·9) and a specificity of 80Â·6% (79Â·2â82Â·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0Â·018 for RNA sequencing and p=0Â·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0Â·0001 by qRT-PCR) with a sensitivity of 53Â·7% (42Â·6â64Â·3) and a specificity of 82Â·8% (76Â·7â86) in 12 months preceding tuberculosis. Interpretation: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. In this prospective cohort study, we followed up healthy, South African adolescents aged 12â18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex qRT-PCR, the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease.

Project description:With increasing incidence of multidrug-resistant tuberculosis (MDR-TB), accurate drug susceptibility testing (DST) of Mycobacterium tuberculosis to first-line drugs has become crucial for proper patient management. We evaluated concordance of DST results for 70 M. tuberculosis isolates across two phenotypic and two molecular methods: BACTEC 460TB, MGIT 960 system, GenoType MTBDRplus and DNA sequencing of gene segments most commonly implicated in conferring resistance to anti-TB drugs. Most (84%) M. tuberculosis isolates were multidrug-resistant. Twenty-four isolates yielded discrepant DST results. For rifampicin, isoniazid and streptomycin, 96%, 97% and 93% of isolates, respectively, were susceptible or resistant by all four methods, whereas for ethambutol, this agreement was observed for only 76% of isolates (P<0.05 for rifampicin or isoniazid or streptomycin versus ethambutol). Occurrence of rare mutations in three isolates that confer low-level resistance caused lower agreement for rifampicin among the four methods (kappa coefficient (?) range, 0.84 to 0.95). For isoniazid, there was perfect agreement among phenotypic methods and molecular methods (?, 1.00) but lower agreement between phenotypic and molecular methods. Three isolates were detected as polydrug-resistant by MGIT 960 system but as multidrug-resistant by DNA sequence-based method. The agreement was higher for streptomycin among the two phenotypic methods (?, 0.97) while targeted sequencing yielded lower agreement (? range, 0.86 to 0.89). The discrepancy for ethambutol resulted largely due to lower concordance of MGIT 960 results (? range, 0.53 to 0.64). The MGIT 960 system is an accurate method for DST of M. tuberculosis against isoniazid and streptomycin while the results of rifampicin susceptibility should be complemented with DNA sequencing-based method when the suspicion for resistance is high. The possibility of false susceptibility to ethambutol with MGIT 960 system suggests that molecular or other phenotypic methods may be more useful when accurate ethambutol susceptibility results are warranted.

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Serial IGRA testing of trainees in the healthcare sector in a country with low incidence for tuberculosis - a prospective cohort study.

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