Screening for Latent Tuberculosis Infection (LTBI) in US Army Recruits

• Sponsor: Uniformed Services University of the Health Sciences (U.S. Fed)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00804713
• Collaborator: Infectious Diseases Clinical Research Program (Other)
• Enrollment: 2,017
• Location: 1
• Arm: 1
• Duration (Months): 161
• Patients Per Site Per Month: 12.5

Study Details

Study Description

Brief Summary

The overall objective of this study is to assess the feasibility and potential impact of using a targeted testing approach and 2 interferon-gamma release assays (IGRA) to screen for latent tuberculosis (TB) infection (LTBI) among military recruits. The current policy of universal application of the Mantoux tuberculin skin test (TST) to screen for LTBI may result in many TST reactions among recruits who are at low risk for LTBI. The central hypothesis is that targeted testing by use of the questionnaire will reduce unnecessary testing of low-risk recruits without affecting the identification of higher-risk recruits. The secondary hypothesis is that many discordant results between the TST and IGRA may be explained by cross-reactivity to non-tuberculous mycobacteria (NTM) with the TST.

Condition or Disease	Intervention/Treatment	Phase
Latent Tuberculosis Infection	Drug: BST; Drug: TST; Other: QFT; Other: T-spot	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 2017 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: All study participants received 4 tests, including the use of two skin tests, one on each arm. However, the participant and outcomes assessors were blinded to which skin test was placed on which arm to avoid bias in assessment of the outcomes.
• Primary Purpose: Screening
• Official Title: Screening for Latent Tuberculosis Infection (LTBI) in US Army Recruits
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Jun 1, 2009
• Anticipated Study Completion Date: Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All study participants Subjects administered the TB skin test, Battey skin test, QFT-GIT, and T-Spot	Drug: BST; 0.1 mcg/mL (1 dose) Battey skin test (BST) antigen administered using the Mantoux method.; Drug: TST; Administer TB Skin test (TST); Other: QFT; Perform QFT TB test; Other Names: Quantiferon Gold-in-tube (QFT) ; Other: T-spot; Perform T-Spot TB test; Other Names: T-spot.TB test

Outcome Measures

Primary Outcome Measures

1. TST Induration Will be Interpreted Relative to Risk, in Accordance With Published CDC Guidelines. [48-72 hrs post administration]

   Risk stratification and test result. Risk was stratified by the use of risk factors identified by questionnaire according to the 5, 10 and 15 mm criteria (CDC Morbidity and Mortality Weekly Report Recommendations and Reports 2000. Targeted Testing for Latent Tuberculosis Infection.) The number of 1803 is used here because that is the number for which valid results were available for all 4 tests. The number presented in each category is the number of participants that had positive results. We are only presented a risk stratified interpretation for the TST (not the QFT, T-spot, and BST) because that is the only test for which this methodology is accepted in scientific and medical use. It is also the only test for which we had pre-specified the use of this methodology in the protocol.

Secondary Outcome Measures

1. Positive QFT-GIT Result [48-72 hours after enrollment]

   The number of subjects is 1781 (less than the original 1978) because we analyzed only those who had valid results by all 4 tests to have a fair comparison. Additionally, we excluded those subject who had a borderline T-Spot result, as we were not able to make valid comparisons with these results.

Other Outcome Measures

1. T-Spot Result [48-72 hours]

   Positive T-Spot results. The number of subjects is 1781 (less than the original 1978) because we analyzed only those who had valid results by all 4 tests to have a fair comparison. Additionally, we excluded those subject who had a borderline T-Spot result, as we were not able to make valid comparisons with these results.

2. Battey Skin Test Result [48-72 hours after administration]

   Battey skin test positive results defined as >= 100 mm reaction. The number of subjects is 1781 (less than the original 1978) because we analyzed only those who had valid results by all 4 tests to have a fair comparison. Additionally, we excluded those subject who had a borderline T-Spot result, as we were not able to make valid comparisons with these results.

3. TST Results for the Population for Which All 4 Tests Have Valid Results and no Borderline Results [48-72 hours after adminstration]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Any recruit, age 18 years or older, undergoing routine entry-level medical processing at Fort Jackson

Exclusion Criteria:

• If they have history of severe reactions to TST (e.g., blistering, scar, or symptoms of immediate hypersensitivity)

• If they are unwilling to provide written consent for the study

• If they are unwilling to provide Health Insurance Portability and Accountability Act (HIPAA) authorization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fort Jackson, SC	Columbia	South Carolina	United States	29207

Sponsors and Collaborators

• Uniformed Services University of the Health Sciences
• Infectious Diseases Clinical Research Program

Investigators

• Principal Investigator: James Mancuso, MD MPH, Uniformed Services University of the Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: James Mancuso, James Mancuso, Uniformed Services University of the Health Sciences
• ClinicalTrials.gov Identifier: NCT00804713
• Other Study ID Numbers: IDCRP-021
• First Posted: Dec 9, 2008
• Last Update Posted: Dec 20, 2021
• Last Verified: Dec 1, 2021

• Keywords provided by James Mancuso, James Mancuso, Uniformed Services University of the Health Sciences: TB; tuberculosis diagnosis; TB screening
• Additional relevant MeSH terms: Infections; Communicable Diseases; Tuberculosis; Latent Tuberculosis

Study Results

Participant Flow

Pre-assignment Detail	39 participants were enrolled but lost to follow-up before skin testing or blood draw were performed. This was due to the administrative requirements of the basic training setting, not because of the study itself.

Arm/Group Title	All Study Participants
Arm/Group Description	Subjects administered the tuberculosis skin test (TST), Battey skin test, Quantiferon Gold-in-tube (QFT-GIT), and T-Spot
Period Title: Overall Study
STARTED	1978
COMPLETED	1978
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Subjects administered the Tuberculosis skin test (TST), Battey skin test, QFT-GIT, and T-spot
Overall Participants	1978
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	21.8 (4.6)
Sex/Gender, Customized (participants) [Number]
Female	681 34.4%
Male	1294 65.4%
Prevalence of tuberculosis (TB) in country of birth (participants) [Number]
<20 per 100,000	1811 91.6%
20-99 per 100,000	62 3.1%
>=100 per 100,000	105 5.3%

Outcome Measures

1. Primary Outcome

Title	TST Induration Will be Interpreted Relative to Risk, in Accordance With Published CDC Guidelines.
Description	Risk stratification and test result. Risk was stratified by the use of risk factors identified by questionnaire according to the 5, 10 and 15 mm criteria (CDC Morbidity and Mortality Weekly Report Recommendations and Reports 2000. Targeted Testing for Latent Tuberculosis Infection.) The number of 1803 is used here because that is the number for which valid results were available for all 4 tests. The number presented in each category is the number of participants that had positive results. We are only presented a risk stratified interpretation for the TST (not the QFT, T-spot, and BST) because that is the only test for which this methodology is accepted in scientific and medical use. It is also the only test for which we had pre-specified the use of this methodology in the protocol.
Time Frame	48-72 hrs post administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Study Participants
Arm/Group Description	Subjects administered the TB skin test Tuberculin Skin Test: Administer TB Skin test, Battey skin test, QFT, and T-Spot
Measure Participants	1803
High	2 0.1%
Medium	37 1.9%
Low	20 1%

2. Secondary Outcome

Title	Positive QFT-GIT Result
Description	The number of subjects is 1781 (less than the original 1978) because we analyzed only those who had valid results by all 4 tests to have a fair comparison. Additionally, we excluded those subject who had a borderline T-Spot result, as we were not able to make valid comparisons with these results.
Time Frame	48-72 hours after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	QFT-GIT
Arm/Group Description	Subjects administered the QFT-GIT TB test QFT-GIT: Perform QFT-GIT TB test
Measure Participants	1781
Positive	36 1.8%
Negative	1745 88.2%

3. Other Pre-specified Outcome

Title	T-Spot Result
Description	Positive T-Spot results. The number of subjects is 1781 (less than the original 1978) because we analyzed only those who had valid results by all 4 tests to have a fair comparison. Additionally, we excluded those subject who had a borderline T-Spot result, as we were not able to make valid comparisons with these results.
Time Frame	48-72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Study Participants
Arm/Group Description	Subjects administered the TB skin test, Battey skin test, QFT-GIT, and T-Spot All study participants: 0.1 mcg/mL (1 dose) Battey skin test antigen administered using the Mantoux method. All study participants: Administer TB Skin test All study participants: Perform QFT-GIT TB test All study participants: Perform T-Spot TB test
Measure Participants	1781
Positive	34 1.7%
Negative	1747 88.3%

4. Other Pre-specified Outcome

Title	Battey Skin Test Result
Description	Battey skin test positive results defined as >= 100 mm reaction. The number of subjects is 1781 (less than the original 1978) because we analyzed only those who had valid results by all 4 tests to have a fair comparison. Additionally, we excluded those subject who had a borderline T-Spot result, as we were not able to make valid comparisons with these results.
Time Frame	48-72 hours after administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Study Participants
Arm/Group Description	Subjects administered the TB skin test, Battey skin test, QFT-GIT, and T-Spot All study participants: 0.1 mcg/mL (1 dose) Battey skin test antigen administered using the Mantoux method. All study participants: Administer TB Skin test All study participants: Perform QFT-GIT TB test All study participants: Perform T-Spot TB test
Measure Participants	1781
Positive	203 10.3%
Negative	1578 79.8%

5. Other Pre-specified Outcome

Title	TST Results for the Population for Which All 4 Tests Have Valid Results and no Borderline Results
Time Frame	48-72 hours after adminstration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Study Participants
Arm/Group Description	Subjects administered the TB skin test Tuberculin Skin Test: Administer TB Skin test, Battey skin test, QFT, and T-Spot
Measure Participants	1781
Positive	48 2.4%
Negative	1733 87.6%

Adverse Events

Arm/Group Title	All Study Participants
Arm/Group Description	Subjects administered the TB skin test, Battey skin test, QFT-GIT, and T-Spot
All Cause Mortality
	All Study Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Study Participants
	Affected / at Risk (%)	# Events
Total	0/1978 (0%)
Other (Not Including Serious) Adverse Events
	All Study Participants
	Affected / at Risk (%)	# Events
Total	0/1978 (0%)

Limitations/Caveats

A limitation of this study is the lack of a gold standard for determining the presence of M. tuberculosis infection, making it difficult to assess the true significance of discordance between TST and the interferon-gamma release assays (IGRAs).

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.