IGRA and Mantoux Response in Children With Suspected Latent or Active TB Infection (TBTubercolar)

May 4, 2017 updated by: Francesca Montagnani, University of Siena

Observational Study to Compare IGRA and Mantoux Test in Children With Suspected Latent or Active TB Infection

The aim of this project is to analyze the potential contribution of IGRA test QuantiFERON-TB Gold In Tube test (QTF-GIT, Cellestis Limited, Carnegie, Victoria, Australia) in the diagnosis of tuberculosis (TB - active or latent) in pediatric subjects (0 and 17 year)s recently exposed to infection (indicated as "contacts") or with clinical suspicion of active TB, and to compare the results obtained with those of the TuberculinSkin Test (TST; gold standard). The project is expected to enroll up to 50 pediatric patients over a 4-year study. Children with access to Ambulatory structures or hospitalized at University Infectious Diseases Clinic or Pediatric Clinic, University Hospital of Siena, or with access to Ambulatory or hospitalized at Pediatric Clinic USL 9 Grosseto will be enrolled. Once obtained the informed consent of patients' parents or legal guardians, patients will be enrolled. The doctor will administer a clinical-anamnestic questionnaire, relative to the country of birth and residence, date of arrival in Italy and any stays in the country of origin (in case of foreign patient), travels abroad, risk factors for infectious diseases, type of contact with any index case, previous vaccination with BCG, date and outcome of the TST, clinical symptoms and signs suggestive of active TB, report of any instrumental investigation. Together with the collection of blood samples for routine purposes, an additional blood sample will be taken so to run IGRA test. Also patients for whom their medical doctor will independently order to run QTF-GIT test as necessary tool for the clinical diagnosis of TB will be included in the study.

A retrospective analysis will be performed on patient pertaining to participant Clinics, from 1 January 2012 to 31 May 2015. Such analysis will be performed on those patients for which their medical doctor requested both intradermal Mantoux and IGRA test.

Expected results:

  • estimation of concordance between QuantiFERON-TB Gold In Tube and TST in pediatric patients exposed to TB, with or without latent TB infection
  • Evaluation of the sensitivity of the test QTF-GIT in patients with active tuberculosis disease
  • Evaluation of specificity of testQTF-GIT in not infected patients
  • Evaluation on the possible use of QTF-GIT, together with TST, to improve the diagnosis of tuberculosis latent or active infection in pediatric subjects.
  • Evaluation of the possible diagnostic use of QTF-GIT in the child <5 years.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The diagnosis of tuberculosis in children is a complex procedure. The commonly used test is the tuberculin skin test (TST), which shows significant limitations such as cross-reactivity with the bacillus Calmette-Guerin (BCG) used for vaccination, and other environmental mycobacteria, the possible influence of age and the immunological status of the patient, the need to return to the hospital for the re-reading of the intradermal reaction. Since 2001, the Food and Drug Administration approved the first of a series of new tests, called Interferon-Gamma Release Assays (IGRAs), based on the release of interferon gamma by sensitized lymphocytes in the blood of the patient. Among them, the QuantiFERON-TBGold In Tube (QTF-GIT, Cellestis Limited, Carnegie, Victoria, Australia), is a highly specific test that measures, through an ELISA assay, the release of interferon-gamma production by lymphocytes in response to an antigenic challenge to Mycobacterium tuberculosis antigens. The antigens used in the test QTF-GIT (ESAT-6, CFP-10 and the sequence of TB7.7) are in fact absent from the vaccine strain BCG and in most nontuberculous mycobacteria, giving to the QTF-GIT test greater specificity than TST. Moreover, being an in vitro test, it does not require a return visit to the reading of the result (this is particularly important in screening of contacts), which is instead carried out in an instrument (and therefore objective) and, finally, thanks to the presence of an internal positive control, it is possible to evaluate the performance of tests and reduce possible technical errors. The QTF-GIT test gave significant results in adults in terms of sensitivity and specificity, as demonstrated by a large scientific literature, and is currently used in many hospitals, in combination with the TST, for the diagnosis of tuberculosis. Since September 2012, also the Siena University Hospital introduced the QTF-GIT assay as a diagnostic test for tuberculosis diagnosis in healthcare workers and in inpatient or outpatient tested positive TST requiring detailed diagnostic investigation (eg. Previous BCG vaccination, suspected atypical mycobacteriosis, eruptive events or other skin changes that contraindicate performing intradermal reaction).

Despite the important results obtained with the test QTF-GIT in adults, studies of specificity and sensitivity of the tests conducted in the pediatric age group are still limited. Some studies have shown a high specificity, while the sensitivity appears lower than the TST. The data are discordant, however, between the different studies, complicated by the fact that there is no real-Gold standard for the diagnosis of latent TB, and hence, further analysis is still needed.

While in adults the risk of progression from latent infection to active pulmonary disease is about 5-10%, in infants (<1 year old) this value increases up to about 30-40%, therefore the diagnosis and the treatment of latent infections is more than ever necessary to reduce the risk of developing the disease. Thus an urgent need to identify specific and sensitive diagnostic tools that would enable better diagnosis of TB in childhood, particularly in the age group under 5 years, as clearly expressed also by the European Centre for Disease Prevention and Control (ECDC) in guidelines "Use of Interferon-gamma release assays in support of TB diagnosis" and by the resolution of the Regional Council of Tuscany Region n. 677 of 8.4.2014.

The aim of this project is to analyze the potential contribution of IGRA test, QuantiFERON-TB Gold In Tube test (QTF-GIT, Cellestis Limited, Carnegie, Victoria, Australia) in the diagnosis of tuberculosis (TB - active or latent) in pediatric subjects aged between 0 and 17 years recently exposed to infection (indicated as "contacts") or with clinical suspicion of active TB, and to compare the results obtained with those of the TuberculinSkin Test (TST), which is the gold standard. The research project is expected to enroll up to 50 pediatric patients (0- 17 years) over a 4-year study. Children with access to Ambulatory structures or hospitalized at University Infectious Diseases Clinic or Pediatric Clinic, University Hospital of Siena, or with access to Ambulatory or hospitalized at Pediatric Clinic USL 9 Grosseto will be enrolled. Once obtained the informed consent of patients' parents or legal guardians, patients will be enrolled. The doctor will administer a clinical-anamnestic questionnaire (CRF), relative to the country of birth and residence, date of arrival in Italy and any stays in the country of origin (in case of foreign patient), travels abroad, risk factors for infectious diseases, type of contact with any index case, previous vaccination with BCG, date and outcome of the TST, clinical symptoms and signs suggestive of active TB, report of any instrumental investigation. Together with the collection of blood samples for routine purposes, an additional blood sample will be taken so to run experimental IGRA test. Also patients for whom their medical doctor will independently order to run QTF-GIT test as necessary tool for the clinical diagnosis of TB will be included in the study.

A retrospective analysis will be performed on patient pertaining to participant Clinics, from 1 January 2012 to 31 May 2015. Such analysis will be performed on those patients for which their medical doctor requested both intradermal Mantoux and IGRA test.

Main objectives:

  1. Estimation of concordance between QuantiFERON-TB Gold In Tube and TST in pediatric patients exposed to TB
  2. Evaluation of the sensitivity of the test QTF-GIT in patients with active tuberculosis disease
  3. Evaluation of specificity of test QTF-GIT in not infected patients

Secondary objectives:

  • Evaluation of the possible use of QTF-GIT, together with TST, to improve the diagnosis of latent or active tuberculosis infection in pediatric subjects.
  • Evaluation of the possible diagnostic use of QTF-GIT in the child, with special attention to children <5 years.

Study Type

Observational

Enrollment (Anticipated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Siena, Italy, 53100
        • Recruiting
        • UOC Malattie Infettive Universitarie c/o Policlinico Le Scotte, Viale Mario Bracci 16
        • Contact:
        • Principal Investigator:
          • Francesca Montagnani, MD, PhD
        • Sub-Investigator:
          • Andrea De Luca, MD
        • Sub-Investigator:
          • Matteo Morandi, PhD
    • GR
      • Grosseto, GR, Italy, 58100
    • SI
      • Siena, SI, Italy, 53100
        • Recruiting
        • UOC Pediatria c/o Policlinico Le Scotte, Viale Mario Bracci 16
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The study will be performed on children hospitalized at Policlinico Santa Maria alle Scotte (Infectious Dieseases and Pediatrics wards), at Pediatric Clinic of Grosseto USL9, and from the ambulatories of the above mentioned hospitals.

Description

Inclusion Criteria:

  • Age between 0 to 17 years
  • Willingness to provide informed consent (parents or legal guardians)
  • Contact with TB case and/or clinical suspect of active TB

Exclusion Criteria:

  • Acquired or congenital immune deficiencies
  • Oncohematologic diseases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Other

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cases

A blood sample necessary to perform QFT-GIT will be taken, together with other routine blood samples, from children with following diagnosis:

  • latent tuberculous infection: active TB contact, TST positive, lack of clinical and RX signs of active-TB
  • active TB: clinical and radiologic evidences of active-TB, positivity to microbial tests to BK
  • not infected: patients evaluated as TB contacts, with negative TST and negative clinical/radiological/microbial results for TB.
Other: IGRA test (QTF-GIT)
blood sample for QFT-GIT will be taken together with other routine blood samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of patients with concordance of QTF-GIT test and TST,among children exposed to TB
Time Frame: up to 4 years
up to 4 years
Number of patients with positivity of QTF-GIT in comparison with TST among children with active tuberculosis disease
Time Frame: up to 4 years
up to 4 years
Number of patients with a negative QTF-GIT test in comparison of TST, among non-infected children
Time Frame: up to 4 years
up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Siena

Investigators

  • Principal Investigator: Francesca Montagnani, PhD, MD, Università di Siena - Azienda Ospedaliera Santa Maria alle Scotte

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2015

Primary Completion (Anticipated)

April 1, 2019

Study Completion (Anticipated)

December 1, 2020

Study Registration Dates

First Submitted

January 3, 2016

First Submitted That Met QC Criteria

January 11, 2016

First Posted (Estimate)

January 12, 2016

Study Record Updates

Last Update Posted (Actual)

May 5, 2017

Last Update Submitted That Met QC Criteria

May 4, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IGRAManPed2014

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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