A Pilot TB Screening Model in a U.S. Prison Population Using Tuberculin Skin Test and Interferon Gamma Release Assay Based on Country of Origin

Abstract

The objective of this study was to compare tuberculosis (TB) screening results before and after implementation of a stratified testing strategy screening pilot study, incorporating interferon gamma release assay (IGRA) and tuberculin skin test (TST), based on country of origin. In 2015, the Washington State Department of Corrections began screening people born outside of the United States for TB with IGRA, while U.S.-born people continued screening by TST. Of 405 (75%) foreign-born men screened with IGRA, 403 had valid test results and IGRA screening positivity was 10.4% (N = 42). In contrast, among 5,940 primarily U.S-born men screened with TST, 24 (0.4%) were positive. Overall positivity was 1.05%, similar to TST-only positivity in 2013 (1.05%) and 2014 (0.85%). Incorporating IGRA screening among foreign-born persons was feasible in this state prison system.

Introduction

The incidence of active tuberculosis (TB) among people in federal and state correctional facilities in the United States was 29.4 and 24.2 cases per 100,000 respectively, compared with 6.7 in the U.S. general population from 1993 to 2003 (MacNeil et al., 2005). There is greater risk of transmission of TB in correctional settings due to the proximity of residents (MacIntyre et al., 1997). The correctional population also is at increased risk for TB infection and active disease because of the higher prevalence of risk factors, such as drug use, lower socioeconomic status, homelessness, and HIV infection (Kim & Crittenden, 2005; MacNeil et al., 2005). To decrease TB transmission in correctional facilities, the Centers for Disease Control and Prevention (CDC, 2006) recommends TB testing of all persons at entry and usually annually thereafter.

On a national level, although the incidence of active TB among people who were born in the United States is decreasing, the incidence among those who are foreign born has stabilized, resulting in a widening disparity in TB incidence over time (Stewart et al., 2018). Similarly, the proportion of people reported with TB in correctional facilities who are foreign born has increased over time, and in 2008 surpassed the proportion of U.S.-born people with TB in correctional facilities for the first time (Lambert et al., 2016).

The Mantoux tuberculin skin test (TST) is the most commonly used screening test for TB in the United States, despite low specificity (Diel et al., 2009; Pai et al., 2008). Interferon-gamma release assays (IGRAs) have higher specificity, especially among populations vaccinated with the bacille Calmette-Guerin (BCG) vaccine (Grinsdale et al., 2016; Gudjónsdóttir et al., 2016). Given that BCG vaccination is common in many countries in which TB prevalence is high, using an IGRA may have significant clinical benefit in the foreign-born population by reducing false-positive results due to cross-reactivity with the BCG. Screening tests with higher sensitivity may correctly identify more people in need of TB treatment, potentially reducing transmission. Although some studies have found IGRA screening tests to be more sensitive (De Keyser et al., 2014; Diel et al., 2010; Pai et al., 2008), others have found comparable sensitivity between IGRA and TST (Cattamanchi et al., 2011; Doan et al., 2017; Kik et al., 2010; Machingaidze et al., 2011).

IGRA screening, however, is more costly than TST; at the time of our pilot study, the cost per test for TST and IGRA (equipment and laboratory costs only) was $2 and $46, respectively. The higher costs of the IGRA test itself are significantly offset in the community setting by avoiding the need for the two clinic visits necessary to both place and then read a TST. The financial savings gained by limiting TB screening to a single visit in a correctional facility are minimal, since there is no billing process for staff time other than salary costs. In addition, a significant number of patients in the community setting fail to come to that second appointment, leading to missing TST results or necessitating the need for additional TB screening (Grinsdale et al., 2011; Wrighton-Smith et al., 2012). The loss to follow-up in a correctional setting is often minimal, decreasing the clinical benefits of IGRA, the more costly TB screening option. Therefore, it can be harder to justify using IGRA for TB screening of an entire correctional population.

At least two U.S. public health departments have implemented IGRA-only TB screening in their community and public health clinics. In San Francisco, TB screening results were obtained for a higher proportion of those screened with IGRA than was the case for historical controls screened with TST (Dewan et al., 2006). In New York City, the proportion of those testing positive with IGRA was lower than previous time periods using TST-only screening; however, this reduction in those with positive results was confined to people born outside of the United States (Stennis et al., 2014).

Based on the reduction in the number of positive tests seen in the community, some correctional systems have compared IGRA with TST results within the same patient cohorts. Several pilot studies have actually shown higher rates of TB infection detected by IGRA than by TST in jails and prisons, but few programs have systematically introduced IGRA testing in the correctional setting (Nijhawan et al., 2016; Porsa et al., 2007; Schwartz et al., 2014).

We piloted a stratified testing strategy TB screening program in a state prison system that we hypothesized would improve the specificity of TB screening, thereby reducing the proportion of false-positive TB screening results and potentially improving cost efficiency. All foreign-born persons (except those born in Canada) entering the prison system were screened for TB with an IGRA at intake and annually thereafter, and all others incoming continued to be screened using a TST. We compared the prevalence of latent TB detected during the year of the pilot study to the prevalence of latent TB detected during previous years, when only TST was used for TB screening.

Method

Washington State Department of Corrections (WA DOC) performs a TB signs and symptoms screen of all persons as they enter the system. If a patient has signs or symptoms concerning for active TB, the patient is immediately isolated and referred to a practitioner. Otherwise, a routine intake medical examination is conducted within 14 days of entry and at the time patients are evaluated for TB. If there is documentation of a prior positive test for TB, the patient has a chest X-ray taken.

From January 2015 to December of 2015, the infection prevention nurses asked patients their country of birth as part of their medical intake. Anyone born outside the United States and Canada was screened for TB with an IGRA (T-SPOT.TB; Oxford Immunotec, Oxfordshire, United Kingdom). All other persons were screened for TB using a TST, using Tubersol antigen solution (TUBERSOL; Sanofi Pasteur, Toronto, Canada). Standard screening cut points were utilized, with a 10 mm induration requiring additional evaluation (Diagnostic Standards and Classification, 2000). Following CDC screening guidelines, a 5 mm cut point was used for the following groups: those living with HIV, recent contacts to TB, people with chest radiography suggest of prior TB disease, and those with organ transplants and other immunosuppressed people. Nursing staff are trained to read TST results by other WA DOC clinical staff.

For those screened with IGRA, the date of screening and test result were recorded. Foreign-born persons with a borderline or invalid IGRA result were retested, but testing was terminated if there was not a definitive result after three tests. For those screened with a TST, the dates the purified protein derivative was placed and read were recorded. Patients who were found to have either a new positive TST or IGRA were referred for chest X-ray and further evaluation. Those who were found to have active TB were isolated and treated per guidelines, and treatment for latent tuberculosis infection (LTBI) was offered to those who were found not to have active disease.

Thereafter, annual screening for TB was conducted during the month of birth, as long as it was at least 6 months since the most recent negative TB screen. If the month of birth was less than 6 months from the intake testing, TB screening was deferred until the month of birth the subsequent year. Annual TB testing was done using the same testing type used at intake, either TST or IGRA; foreign-born individuals who entered the system before the pilot study continued to be screened annually with TST. For this analysis, we evaluated TB screening at WA DOC entry only.

Statistical Analysis

We also obtained aggregated TST placement and result data for men collected from 2013 to 2015. Thus, we present results from our pilot study for men only to be comparable with these historical data. Data analyses took place from 2016 to 2018. We calculated overall TB screening positivity during the pilot program and compared this with TST positivity at intake from 2013 to 2015. For 2015, we combine all screening tests (TST and IGRA) and results to calculate an overall annual positivity and compare this combined positivity with the TST-only positivity for 2013 and 2014. However, we were not able to determine how many men entered the prison with a history of a positive TST who did not get repeat TST during the historical control time period.

We examined IGRA positivity among foreign-born people by region of birth. We used only the final IGRA result for individuals whose initial IGRA produced a borderline or invalid result. We utilized the United Nations Statistics Division (n.d.) classification system to categorize country of birth into continental regions. In practice, to simplify implementation of a stratified testing TB screening strategy, we classified everyone born outside of the United States and Canada as foreign born, regardless of BCG vaccination practices.

This analysis was performed as part of an operational change to evaluate implementation with deidentified data and, therefore, was exempt from institutional review board review. The pilot analysis was reviewed and approved by the WA DOC Research and Data Division.

Results

During 2015, of the 7,804 persons who entered prison, 562 (7%) were known to be foreign born. Among the entering foreign-born persons, 540 were male, 405 (75%) were screened with IGRA, and 403 received a valid test result (Table 1). The remaining 135 foreign-born men were presumably inadvertently screened by TST instead; however, because all TST results were deidentified, results for specific patients were not identifiable. Conversely, a small number (N = 15) of U.S.- and Canadian-born men were screened with an IGRA; those results are excluded from this table.

Table 1.

Interferon-Gamma Release Assays Testing and Results Among Foreign-Born Population, by Region and Country of Origin, Male Washington State Corrections Population, 2015

	Total	Not tested		Tested		Tested, excluding those with borderline or invalid results	Results among those tested
							Positive
	N	N	%	N	%	N	N	%
Europe	86	21	24	65	76	64	6	9.4
Africa	51	14	27	37	73	36	7	19.4
Asia	87	26	30	61	70	61	9	14.8
Latin America and Caribbean	253	42	17	211	83	211	20	9.5
Oceania	18	9	50	9	50	9	0	0
United States Possessions*,^	45	23	51	22	49	22	0	0
Total**	540	135	25	405	75	403	42	10.4

^{*,^} Includes American Samoa, Guam, N Mariana Island, Puerto Rico, U.S. Virgin Islands.

^** The totals exclude six individuals not tested listed as having “unknown” country of birth or “other countries.”

Among the 403 foreign-born men screened with IGRA, 42 (10.4%) had positive results. When broken out by region of birth, IGRA positivity was highest in people born in Africa (19.4%) and Asia (14.8%). IGRA-tested persons from Latin American and European countries had lower rates of positivity (9.4% and 9.5%, respectively). Among the small number of people born in U.S. dependencies or Oceania, none had a positive IGRA test result.

Overall, a total of 6,357 screening tests (both IGRA and TST) were performed at intake among men in 2015, and 67 (1.05%) were positive. This is similar to the positivity of 1.05 and 0.85 observed in 2013 and 2014, respectively, when the only screening test was TST. In 2015, among the 5,940 mainly U.S.-born men who were screened with TST, only 24 (0.4%) were positive (Table 2).

Table 2.

Positive Tuberculosis Screening Results Before and During Interferon-Gamma Release Assays Pilot Study, Male Washington State Corrections Population, 2013–2015

Year	TST, N	New positive TST results, N	TST positivity	IGRA, N	New positive IGRA results, N	IGRA positivity	Total positive TB screening results, N	Percent screening positive with either TST or T-Spot
2013	6576	69	1.05				69	1.05
2014	6434	55	0.85				55	0.85
2015	5940	24	0.40	417	43	10.3	67	1.05

Not restricted to foreign-born men; excludes those with an invalid/borderline result.

IGRA = interferon-gamma release assays; TB = tuberculosis; TST = tuberculin skin test.

A small number of men screened with IGRA received multiple tests as a result of having invalid or borderline test results on their initial IGRAs (Table 3). Of 14 men with an initial invalid IGRA result, 1 was U.S. born and was not tested a second time with IGRA. Of the 13 foreign-born people with an invalid IGRA result, only 1 (7.7%) eventually tested positive. Of the 20 men with an initial borderline result, 15 (75%) had a repeat negative result, 3 (15%) had a positive result, and 2 (10%) remained borderline on subsequent tests.

Table 3.

All Interferon-Gamma Release Assays Test Results, and Final Results for Borderline or Invalid Results, Male Washington State Corrections Population, 2015

Initial test result	Total, N	%	Final result	N	%
Positive	40	9.5	Negative	12	92.3
Negative	346	82.4	Positive	1	7.7
Invalida	14	3.3	Negative	15	75.0
			Positive	3	15.0
Borderline	20	4.8	Borderline	2	10.0
	420

^a One person with an invalid test result was from the United States. and did not have a follow-up (IGRA) test.

Not restricted to foreign-born men.

Of note, among those with an initial invalid IGRA result, nine (64.3%) occurred during the first 3 months of implementation of the stratified testing program and four (28.6%) occurred during the second quarter. During the pilot study, there was only one invalid IGRA result during the second half of the year. Of the 20 initial borderline IGRA results, 7 (35.0%), 8 (40.0%), and 5 (25.0%) occurred during the first, second, and last quarters of the year, respectively. Of 420 total individuals tested with IGRA, 376 (92.8%) had one test, 39 (9.3%) had two tests, 4 (1.0%) were screened three times, and 1 (0.2%) was screened four times. In addition, two people who initially tested positive with IGRA were unnecessarily tested a second time.

Discussion

In our pilot study in a state prison population, we used IGRA to screen 403 (74.6%) foreign-born individuals, and found that of men screened, 10.4% had a positive result. IGRA positivity was much higher among people from some regions of the world than others, as expected based on the known baseline variance in the prevalence of TB by geographical location. Thirty-four (8.4%) men screened with IGRA had an initial invalid or borderline result, requiring further screening. Invalid IGRA results decreased in frequency over the pilot time period, suggesting an operational learning curve, with subsequent decreased need for and costs associated with repeat testing over time as staff became more comfortable with new processes. In addition, from a health care system perspective, the stratified testing strategy model was easier to accommodate in the historically nurse-based TB screening process as it only converted to a laboratory-based screening for a small subset of the population.

We expected that using IGRA to screen foreign-born persons in our stratified testing strategy pilot study would reduce the proportion of positive TB screening results, thereby requiring fewer individuals be evaluated to rule out active TB. However, we observed an overall positivity (TST and IGRA combined) during the pilot study that was comparable with historical controls screened with TST only during the preceding 2 years. There are several potential explanations for this finding. It may be that the prevalence of BCG vaccination was lower in the Washington State corrections population than among other immigrant and corrections populations studied. However, 85% of foreign-born persons tested with IGRA were born in countries in which BCG is in use, and when we compared positivity among people from countries that do and do not recommend the BCG, we saw no difference (data not shown). Alternatively, if the people vaccinated with BCG had been vaccinated many years ago, we might expect the TST and IGRA results to be similar, given reports of waning BCG cross-reactivity with TST after 15 or more years (Mancuso et al., 2017; Menzies, 2000).

It may also be that the foreign-born share of the Washington State corrections population, being relatively small (6.5%), did not significantly impact overall positivity during our pilot study. The foreign-born group had a positivity 25 times that of the U.S.-born population and the combined positivity for foreign- and U.S.-born population was more than twice that seen for U.S.-born people alone. However, based on studies that have compared IGRA and TST in immigrant populations, we would expect to see a positivity approximately 21% lower with IGRA screening than with TST among people born outside of the United States (Campbell et al., 2015; Miramontes et al., 2015). Thus, we would expect that using TST to screen foreign-born people during our pilot study would have resulted in an additional 11 cases in this group and an overall positivity of 1.23 for the pilot period. Although this “expected” positivity with total TST screening is somewhat higher than the overall positivity we observed during the pilot study, it is not substantially different.

However, the most likely explanation is that the proportion of positive TB screening results was artificially inflated in the pilot period compared with the historical control period, since during the control period persons reporting a prior positive TST were diverted from repeat testing, while during the pilot study a person reporting a prior positive TST still received IGRA testing, thus enriching the pilot-tested population with positive tests while decreasing the overall number of patients requiring further evaluation for LTBI. Unfortunately, with the historical nature of the control group and the limited data available, it is not possible to make this direct comparison.

It may be the case that the greater specificity of IGRA in specific populations justifies its use in the foreign-born portion of our corrections population despite its higher cost, given the higher prevalence of LTBI among immigrants and the importance of detecting and treating LTBI in this population, particularly in the corrections setting where the risk of TB transmission is high. The higher cost of the test may also be offset by the expected reduction in costs related to medical evaluations required as a result of false-positive TST results. This risk-stratfied testing model maximizes the benefits of IGRA in the population most likely to have LTBI and most likely to have had confounding BCG vaccination—the foreign born—while minimizing the cost of screening in the lower risk and larger U.S.-born population. We found this model to be feasible and anecdotally acceptable to both clinicians and those being screened.

For others considering adopting such a strategy, consideration should also be given to the requirements for ongoing annual screening. As we noted, during our pilot study some foreign-born people received TST, whereas some U.S.-born men were screened with IGRA. Using two different tests for annual screening may result in people being screened with different tests over time, and perhaps receiving different results, and requiring further evaluation as a result. The Centers for Disease Control and Prevention (2006) recommends two-step skin testing for incarcerated persons to reduce misclassification of remote exposure as recent skin test conversions suggesting recent infection. In settings where two-step testing is performed, use of IGRA testing in a stratified testing approach would reduce the need for resource-intensive two-step testing in the population receiving IGRA tests. In the Washington State prison setting, the majority of new prisoners have received a recent TST in jail before prison admission and thus the two-step TST is not routinely practiced.

Limitations

Our operational pilot study had several limitations. Country of birth was not available for people in our historical control group; thus, we are not able to directly compare TST and IGRA positivity among foreign-born persons. In addition, as already noted, we were unable to identify the number of persons in the historical control group who had a prior positive TST and, therefore, did not have repeat TST upon entry, but instead had a chest X-ray after screening for signs and symptoms. We were also unable to age adjust our positivity results due to the aggregate nature of our TST data. Furthermore, although Canadian guidelines call for BCG vaccination for infants in high incidence communities (Behr & Elwood, 2014), we categorized Canadian people with U.S.-born people to receive TST in our pilot study. This may have contributed to the higher than expected positivity that we found. Finally, although we could not individually ascertain BCG status for foreign-born persons, we were able to categorize them based on country of birth and each country's recommendation regarding routine BCG vaccination; the vast majority of foreign-born incarcerated persons were born in countries where BCG is routinely provided.

Given the continuing high burden of TB in corrections settings, finding effective strategies to identify persons in correctional facilities with LTBI or active TB is a public health imperative. In our study in a real-world corrections setting, the use of IGRA to screen foreign-born people for TB may not have resulted in lower overall TB positivity. However, a prospective study in which patients are simultaneously screened by both TST and IGRA at intake is needed to directly compare positivity rates in a TST-only, IGRA-only, and a stratified testing strategy system. Creative approaches to screening based on population level risk of LTBI are needed. Many correctional facilities have continued the TST-only screening model, whereas others have switched to a much more costly IGRA-only model. Our stratified testing strategy, employing both TST and IGRA, provides an opportunity to maximize cost-effectiveness while improving the ability to accurately detect and treat LTBI in those populations most affected by TB.

Author Disclosure Statement

The authors disclosed no conflicts of interest with respect to the research, authorship, or publication of this article.

Funding Information

This study was funded by U.S. Department of Health and Human Services, National Institutes of Health, and National Institute of Allergy and Infectious Diseases. Dr. Kerani was supported by NAID K01 AI095060. Dr. Shapiro was supported by NIH grants NIAID T32AI007140 and NIAID K23AI140918.