Tuberculosis screening programme using the QuantiFERON®-TB Gold test and chest computed tomography for healthcare workers accidentally exposed to patients with tuberculosis

doi:10.1016/j.jhin.2010.11.012

Journal of Hospital Infection

Volume 77, Issue 3, March 2011, Pages 257-262

https://doi.org/10.1016/j.jhin.2010.11.012 Get rights and content

Summary

Healthcare workers (HCWs) have an increased incidence of tuberculosis (TB). Periodic and as-needed screenings of HCWs exposed to patients with TB are important. We integrated chest computed tomography (CT) and the QuantiFERON^®-TB Gold (QFT-G) test into our TB screening programme for HCWs. First, contacts were tested using the QFT-G test. Those positive for the QFT-G test were investigated by CT and classified as having active, latent (LTBI), or old TB. Between April 2005 and April 2010, 11 patients who had not been diagnosed with active TB on admission were found to have the disease. A total of 512 close or high risk contacts were identified, and underwent screening. Out of those, 34 (6.64%) were QFT-G positive, whereas 478 (93.36%) were negative. Of the 34 QFT-G-positive HCWs, four had CT findings compatible with active TB and received multidrug treatment; 24 showed no findings of active TB and received isoniazid for six months. All completed their regimens without any adverse effects. The TB screening programme integrating CT and the QFT-G test was safe and feasible. The efficacy of the programme needs to be confirmed by large scale clinical trials.

Introduction

Healthcare-associated transmission of tuberculosis (TB) is a serious issue.1, 2 Healthcare workers (HCWs) have been reported to show a high incidence of TB, which was probably transmitted by accidental exposure to patients with TB.3, 4, 5, 6 In turn, this creates a risk for the patients receiving care from these HCWs. Periodical or pre-employment screenings of all HCWs, in addition to as-needed screenings of HCWs accidentally exposed to patients with TB, are important.³

Tuberculosis infection may be active or latent (LTBI); the former presents symptoms or other indications of disease, whereas the latter is silent. The diagnosis of active TB is straightforward: signs and symptoms, or chest radiograph findings are confirmed by culture or polymerase chain reaction tests. However, the diagnosis of LTBI is not as simple. This is suspected as a result of an enhanced reaction to the tuberculin skin test (TST), but there is no procedure for confirming diagnosis. The classification of TB determines the regimen of the treatment required. Active disease is treated with multiple antituberculosis drugs, whereas LTBI is treated with isoniazid (INH) monotherapy.

The treatment scheme stated above has been widely acknowledged and used. Nevertheless, there is a risk of undertreatment due to insufficient sensitivity of chest radiographs for detecting active TB; patients may be diagnosed as having LTBI and treated only by INH. There is also a risk of overtreatment due to the insufficient specificity of TST for detecting LTBI; a positive TST can be either due to bacille Calmette–Guérin (BCG) vaccination or infection with non-tuberculous mycobacteria. As a result, patients who have not been exposed to TB may be treated by INH. This is especially relevant to the countries with a high BCG vaccination rate such as Japan (96.5%).⁷ The addition of chest computed tomography (CT) will increase the sensitivity of TB disease detection, and replacement of the TST with the QuantiFERON^®-TB Gold (QFT-G) will increase the specificity in detecting LTBI, thus enabling more precise treatment. We therefore integrated chest CTs and the QFT-G test into our TB screening programme for HCWs. First, contacts were tested using the QFT-G test; those who tested negative were excluded. Positive contacts were investigated by CT and classified as having active, latent or old TB. Finally, those with active TB were treated with a multidrug regimen [INH, rifampicin (REF), ethambutol (EB), and pyrazinamide (PZA)], whereas those with LTBI were treated with INH monotherapy. We retrospectively investigated the utility, safety, and feasibility of this programme that has been conducted at the Saitama Medical University Hospital (SMUH) for five years.

Section snippets

Infection Control Subcommittee for Tuberculosis (ICST)

The SMUH is a 712-bed general hospital for patients with acute or subacute illnesses. It does not have a ward dedicated to patients with TB. The ICST was organised in April 2005 by members of the Infection Control Team with experts on TB control, and has been responsible for the TB screening programme.

Traced contacts

The TB screening programme has been active from April 2005 to the present. The programme is conducted by the ICST: once every two years, targeting HCWs who have worked in an infectious disease

TB screening programme

Between April 2005 and April 2010, 11 patients who had not been diagnosed with active TB on admission were later found to have the disease. The ICST conducted the TB screening programme for HCWs in the infectious disease ward twice, and an additional 11 times for HCWs who could have had accidental exposures (Table I). A total of 512 close contacts and high risk contacts underwent screening; 34 (6.64%) had a positive QFT-G test, and 478 (93.36%) were negative. Of the 34 QFT-G positives, four had

Discussion

The combination of the QFT-G test and chest CT is widely used in the clinical practice of TB diagnosis. However, there are no reported TB screening procedures that integrate both the QFT-G and chest CT in the healthcare setting. This prompted us to design the procedures reported in the current study.

The QFT-G test has greater specificity than the TST in detecting current or past history of exposure to M. tuberculosis; thus, we obtained chest CT scans of all contacts with positive QFT-G test

Conflict of interest statement

None declared.

Funding source

This study was performed using research funds of the Saitama Medical University.

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To evaluate the use of computed tomography (CT) and low-dose CT in the detection of latent tuberculosis (TB).
A systematic search of literature in adherence with the PRISMA guidelines was carried out. Quality assessment of the included studies was conducted.
The search strategy identified a total of 4,621 studies. Sixteen studies were considered eligible and included in the review. There was high heterogeneity among all studies. CT was identified as much more sensitive for the detection of latent TB in all studies despite chest radiography often being recommended in guidelines to assess patients for latent TB. Low-dose CT showed promising results in four of the studies; however, these results were limited due to small sample sizes.
CT is much superior to chest radiography consistently identifying additional cases of latent TB. There are limited high-quality publications available using low-dose CT but findings thus far suggest low-dose CT could be used as an alternative to standard-dose CT for the detection of latent TB. It is recommended that a randomised controlled trial investigating low-dose CT should be carried out.
Limited benefit of CT scans in tuberculosis contact tracing
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Citation Excerpt :
Computed tomography (CT) has been recognized as a tool for the detection of minimal changes of lung diseases and has been used to detect tuberculosis diseases at the time of contact investigation [1–8], especially among contacts of patients with multi-drug–resistant (MDR) tuberculosis [9], together with biomarkers [10,11].
The detection of abnormal findings on computed tomography (CT) scans of tuberculosis contacts combined with normal plain radiographs contributes to the early detection of tuberculosis. However, the benefit of the early detection of abnormalities for the prevention of active tuberculosis during follow-up requires evaluation.
We conducted retrospective comparison of the existence of CT scans of tuberculosis contacts without findings of active tuberculosis on plain radiographs at a hospital in Japan. Results: Among 243 contacts without CT scans, five developed tuberculosis during follow-up. Among 229 contacts with CT scans, 24 were judged as targets of multi-drug therapy since their CT findings were suggestive of active tuberculosis at the time of the CT screening. Among 205 contacts judged as having latent tuberculous infection with CT screening, three developed tuberculosis diseases during follow-up. Conclusion: CT scans detected abnormal findings among contacts without abnormalities of plain radiographs but there were some contacts that developed tuberculosis diseases among those with contact investigation including CT scan. The value of CT is equivocal considering the balance of true treatment, overtreatment and harm of radiation.
Usefulness of Quantiferon-TB Gold in Tube® in screening for latent tuberculosis infection in health workers
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El personal sanitario se considera un colectivo de riesgo por estar más expuesto a la enfermedad tuberculosa. La prueba de la tuberculina (PT) presenta el inconveniente del alto número de falsos positivos, sobre todo en pacientes vacunados con BCG. En los últimos años las técnicas denominadas IGRAS parecen mejorar estos inconvenientes, si bien plantean otros dilemas. Nuestro objetivo es analizar la concordancia de ambos test y realizar un estudio de coste-beneficio de las posibles estrategias diagnósticas.
Entre enero de 2010 y octubre de 2011 se estudió todo el personal sanitario del Hospital Universitari Mútua Terrassa de nueva incorporación y aquellos que tenían su revisión laboral. También se estudiaron trabajadores que habían sido contactos de pacientes ingresados con tuberculosis, sin aislamiento inicial. En todos los casos se realizó la PT y paralelamente un Quantiferon-TB Gold in Tube^® (QF-G-IT) en sangre. Se consideró positiva una PT ≥ 10 mm y un QF-G-IT > 0,35 IU/ml. Se descartó enfermedad tuberculosa en todos los profesionales mediante radiología de tórax. Se hizo un estudio de coste beneficio de 3 estrategias posibles de estudio de la infección latente tuberculosa (ILT).
Se estudiaron 226 profesionales sanitarios, con una media de edad de 30,65 ± 16 años. Cuarenta y cuatro (19,4%) presentaban vacuna con BCG, y en 8 (3,5%) se desconocía. La PT fue positiva en 33 (14,6%) casos y el QF-G-IT en 17 (7,5%). En 15 casos ambos valores de la PT y del QF-G-IT fueron positivos y coincidentes. En 18 (8%) profesionales la PT fue positiva, con un valor de QF-G-IT negativo. La concordancia entre ambas pruebas fue del 91%, con un kappa de 0,55. En vacunados, la concordancia fue del 70,5%, con un kappa de 0,33, mientras que en no vacunados fue del 98,9%, con un kappa de 0,65. La estrategia de cribado de la ILT más económica fue la basada en la PT, pero seguida muy de cerca por la estrategia basada en la PT con reconfirmación de los positivos con QF-G-IT, que fue la que mostró un mejor coste-beneficio ya que reduce profilaxis innecesarias.
El QF-G-IT parece ser una técnica adecuada en la detección de la ILT y permite detectar los falsos positivos de la PT debidos a la vacuna con BCG. En este colectivo el QF-G-IT podría ser la prueba idónea para detectar a los realmente infectados y evitar así quimioprofilaxis innecesarias. La estrategia que mostró ser más coste-beneficio fue la basada en la PT con reconfirmación de los casos positivos mediante QF-G-IT.
Healthcare workers (HW) are considered a risk group for exposure to tuberculosis. Screening for latent tuberculosis infection (LTBI) is mandatory in all HW. The Tuberculin test (TT) has been used up until now for LTBI screening, but gives a high number of false positives, especially in patients vaccinated with BCG. Diagnostic methods based on detection of specific gamma interferon (IGRA) have recently appeared on the market in order to improve these drawbacks, but pose other dilemmas. The aim of this study is to determine the agreement between the two types of test and to carry out a cost-benefit study of the possible diagnostic strategies.
All newly hired HW by the Hospital Universitari Mútua Terrassa between January 2010 and October 2011 we were included in the study, as well as those who had their occupational review. Workers who been in contact with patients admitted with tuberculosis before the initial isolation were also tested. In all cases a parallel TT and serum QuantiFeron-TB Gold-in-Tube^® (QF-G-IT) assays were performed. TB disease was ruled out in all professional by chest X-ray. The TT was considered positive when it was equal to or more than 10 mm and if the QF-G-IT was 0.35 IU/mL. A cost-effectiveness analysis was designed with three possible strategies to detect LTBI in order to find the one with the best cost-benefit.
A total of 226 HW were studied, with a mean age 30.65 ± 16, of whom 44 (19.4%) had previous BCG vaccination history, and 8 (3.5%) unknown. The TT was positive in 33 (14.6%) cases and the QF-G-IT in 17 (7.5%). The values of the TT and QF-G-IT were both positive in 15 cases. In 18 (8%) The TT was positive in 18 (8%) of cases with a negative QF-G-IT value. The agreement between the two tests was 91%, with a Kappa of 0.55. In vaccinated cases, the correlation was 70.5%, with a Kappa of 0.33, while in unvaccinated it was 98.9% with a Kappa of 0.65. The cheapest screening strategies for LTBI diagnosis were those based on TT, but followed closely by the strategy based on TT with reconfirmation of positives with QF-G-IT.
QF-G-IT seems to be a very sensitive technique to detect LTBI and allows false positives due to TT to be detected, particularly in BCG vaccinated HW. In this group QF-G-IT could be the ideal test to detect truly infected staff, and avoid unnecessary chemoprophylaxis. The most cost-benefit strategy was those based in TT with reconfirmation or rejection of positive cases by QF-G-IT.
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Journal of Hospital Infection

Summary

Introduction

Section snippets

Infection Control Subcommittee for Tuberculosis (ICST)

Traced contacts

TB screening programme

Discussion

Conflict of interest statement

Funding source

References (16)

Utility of CT in the evaluation of pulmonary tuberculosis in patients without AIDS

Chest

Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review

Lancet Infect Dis

Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005

MMWR Recomm Rep

Recommendations from the National Tuberculosis Controllers Association and CDC

MMWR Recomm Rep

Risk of latent TB infection in individuals employed in the healthcare sector in Germany: a multicentre prevalence study

BMC Infect Dis

Tuberculosis among health-care workers in low- and middle-income countries: a systematic review

PLoS Med

Mycobacterium tuberculosis infection in health care workers in rural India: comparison of a whole-blood interferon gamma assay with tuberculin skin testing

J Am Med Assoc

Screening for tuberculosis infection using whole-blood interferon-gamma and Mantoux testing among Japanese healthcare workers

Infect Control Hosp Epidemiol

Cited by (20)

CT in the detection of latent tuberculosis: a systematic review

Limited benefit of CT scans in tuberculosis contact tracing

Usefulness of Quantiferon-TB Gold in Tube® in screening for latent tuberculosis infection in health workers

CT and <sup>18</sup>F-FDG PET abnormalities in contacts with recent tuberculosis infections but negative chest X-ray

Chest computed tomography scan as an initial diagnostic method for tuberculosis infection detected by mass screening

Chest radiographs and CT findings during healthcare workers’ tuberculosis screening using interferon-gamma release assay: Retrospective observational study