Latent Tuberculosis Infection
Conditions
Keywords
TB, tuberculosis diagnosis, TB screening
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.
Interventions
Sponsors
Infectious Diseases Clinical Research Program
Henry M. Jackson Foundation for the Advancement of Military Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
DOUBLE (Subject, 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| TST Results for the Population for Which All 4 Tests Have Valid Results and no Borderline Results | 48-72 hours after adminstration | — |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Subjects administered the Tuberculosis skin test (TST), Battey skin test, QFT-GIT, and T-spot | 1,978 |
| Total | 1,978 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 21.8 years STANDARD_DEVIATION 4.6 |
| Prevalence of tuberculosis (TB) in country of birth >=100 per 100,000 | 105 participants |
| Prevalence of tuberculosis (TB) in country of birth 20-99 per 100,000 | 62 participants |
| Prevalence of tuberculosis (TB) in country of birth <20 per 100,000 | 1811 participants |
| Sex/Gender, Customized Female | 681 participants |
| Sex/Gender, Customized Male | 1294 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1,978 |
| serious Total, serious adverse events | 0 / 1,978 |
Outcome results
Primary
TST Induration Will be Interpreted Relative to Risk, in Accordance With Published CDC Guidelines.
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Study Participants | TST Induration Will be Interpreted Relative to Risk, in Accordance With Published CDC Guidelines. | Low | 20 participants |
| All Study Participants | TST Induration Will be Interpreted Relative to Risk, in Accordance With Published CDC Guidelines. | High | 2 participants |
| All Study Participants | TST Induration Will be Interpreted Relative to Risk, in Accordance With Published CDC Guidelines. | Medium | 37 participants |
Secondary
Positive QFT-GIT Result
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Study Participants | Positive QFT-GIT Result | Positive | 36 participants |
| All Study Participants | Positive QFT-GIT Result | Negative | 1745 participants |
Other Pre-specified
Battey Skin Test Result
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Study Participants | Battey Skin Test Result | Positive | 203 participants |
| All Study Participants | Battey Skin Test Result | Negative | 1578 participants |
Other Pre-specified
T-Spot Result
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Study Participants | T-Spot Result | Positive | 34 participants |
| All Study Participants | T-Spot Result | Negative | 1747 participants |
Other Pre-specified
TST Results for the Population for Which All 4 Tests Have Valid Results and no Borderline Results
Time frame: 48-72 hours after adminstration
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Study Participants | TST Results for the Population for Which All 4 Tests Have Valid Results and no Borderline Results | Positive | 48 participants |
| All Study Participants | TST Results for the Population for Which All 4 Tests Have Valid Results and no Borderline Results | Negative | 1733 participants |