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. 2024 Apr 16;19(4):e0298628. doi: 10.1371/journal.pone.0298628

Interpreter usage and associations with latent tuberculosis infection treatment acceptance and completion in the USA among non-U.S.–born persons, 2012–2017

Rebeca Gonzalez-Reyes 1, Dolly Katz 2, Lauren Lambert 2, Yoseph Sorri 3, Masahiro Narita 3,4, David J Horne 4,*; for the Tuberculosis Epidemiologic Studies Consortium
Editor: Lisa Kawatsu5
PMCID: PMC11020400  PMID: 38625902

Abstract

Background

Latent tuberculosis infection (LTBI) screening and treatment interventions that are tailored to optimize acceptance among the non-U.S.–born population are essential for U.S. tuberculosis elimination. We investigated the impact of medical interpreter use on LTBI treatment acceptance and completion among non-U.S.–born persons in a multisite study.

Methods

The Tuberculosis Epidemiologic Studies Consortium was a prospective cohort study that enrolled participants at high risk for LTBI at ten U.S. sites with 18 affiliated clinics from 2012 to 2017. Non-U.S.–born participants with at least one positive tuberculosis infection test result were included in analyses. Characteristics associated with LTBI treatment offer, acceptance, and completion were evaluated using multivariable logistic regression with random intercepts to account for clustering by enrollment site. Our primary outcomes were whether use of an interpreter was associated with LTBI treatment acceptance and completion. We also evaluated whether interpreter usage was associated treatment offer and whether interpreter type was associated with treatment offer, acceptance, or completion.

Results

Among 8,761 non-U.S.–born participants, those who used an interpreter during the initial interview had a significantly greater odds of accepting LTBI treatment than those who did not use an interpreter. There was no association between use of an interpreter and a clinician’s decision to offer treatment or treatment completion once accepted. Characteristics associated with lower odds of treatment being offered included experiencing homelessness and identifying as Pacific Islander persons. Lower treatment acceptance was observed in Black and Latino persons and lower treatment completion by participants experiencing homelessness. Successful treatment completion was associated with use of shorter rifamycin-based regimens. Interpreter type was not associated with LTBI treatment offer, acceptance, or completion.

Conclusions

We found greater LTBI treatment acceptance was associated with interpreter use among non-U.S.–born individuals.

Introduction

In 1989, the Centers for Disease Control and Prevention (CDC) established the domestic goal of tuberculosis (TB) elimination (defined as TB incidence <1 per 1 million persons) by 2010. In 2021, TB incidence in the United States was 2.37 cases per 100,000 persons, a level more than 20 times that required for TB elimination [2]. One explanation for the slow progress towards US TB elimination was a shift in the epidemiology of TB in the United States: in 1993 only 29% of TB occurred in non-U.S.–born individuals while in 2021 the frequency was 71% [1, 2]. Latent TB infection (LTBI) screening and treatment interventions that are tailored to optimize acceptance among persons who are non-U.S.–born will be essential for TB elimination in the United States.

LTBI treatment is highly effective in preventing progression of LTBI to TB disease [3]. A recent study by the Tuberculosis Epidemiologic Studies Consortium (TBESC) found that only 32% of individuals diagnosed with LTBI completed treatment [4]. Evaluating the stages of the cascade of care for LTBI treatment may identify where patient losses occur [5]. In the TBESC study, although there were losses at each care-cascade step, the biggest drop-off was seen at treatment initiation. Given high TB [2] and LTBI [6] rates in non-U.S.–born persons compared to U.S.-born populations, it is important to understand barriers to LTBI treatment and completion that are unique to non-U.S.–born persons, many of whom are not native English speakers.

Lack of English proficiency may lead to miscommunications between physicians and other providers with patients, lowers the number of healthcare visits, and generates lower patient satisfaction [7]. Across different medical settings, the use of professional interpreters has been shown to be associated with decreased communication errors, greater patient comprehension and satisfaction, and improved clinical outcomes [7]. Additionally, lack of English proficiency creates a language barrier that further promotes health disparities that exist among people who are at higher risk for LTBI and TB. There are few published studies on the effects of limited English proficiency on the LTBI treatment care cascade. A 2019 systematic review of U.S. healthcare-based strategies to improve LTBI testing and linkage to care in non-U.S.–born groups [8] identified one study that evaluated interpreter usage. In this study, language concordance between patients and providers was compared to use of a trained interpreter and found no difference in referrals for LTBI testing or receipt of testing [9]. A study in Sweden found that interpreter-assisted appointments were associated with higher rates of completion of LTBI treatment among persons seeking asylum [10].

Given the importance of addressing healthcare inequities and improving outcomes across the LTBI care continuum in non-U.S.–born persons, we investigated associations between the use of trained medical interpreters and LTBI treatment acceptance and completion in a TBESC study as our primary outcomes. We hypothesized that the use of a trained medical interpreter during the initial interview when LTBI treatment was discussed and offered would increase LTBI treatment acceptance and completion. We also investigated whether use of a trained interpreter was associated with clinician decisions to offer treatment and whether interpreter type was associated with LTBI treatment offer, acceptance, or completion.

Methods

Study population and design

TBESC enrolled children and adults from July 20, 2012 to May 5, 2017, across 18 TBESC-affiliated clinics in 11 U.S. states to compare LTBI diagnostics and assess their predictive capabilities to detect progression of those with LTBI to TB disease [11]. All participants were considered to be at high risk for LTBI or progression to TB disease and included persons who were (a) close contacts of persons with infectious TB; (b) born in countries whose populations residing in the United States had high (≥100 cases/100,000 population) TB rates [12]; (c) recent arrivals (≤5 years) from countries whose populations residing in the United States had moderate (10–99 cases/100,000 population) TB rates [12]; (d) visitors of ≥30-day duration during the previous 5 years to countries whose populations had high TB rates; (e) living with HIV infection; (f) immigrants and refugees who had an abnormal chest radiograph result during the immigration process; and (g) members of a population with local LTBI prevalence of ≥25% [11]. For participants with more than one eligibility criterion, a hierarchy of enrollment reasons was established to assign a category to this variable in regression models: 1) close contact of person with infectious TB, 2) non-U.S.–born person from a high-risk country or recently arrived from medium risk country (S1 Table), 3) visitor of ≥30 days in a high-risk country during prior 5 years, 4) person belonging to a population with a LTBI prevalence ≥25%, and 5) person living with HIV.

Study staff collected blood for two FDA-approved interferon-gamma release assays (IGRAs), the QuantiFERON-TB Gold In-Tube (QFT-GIT, Qiagen Diagnostics; Hamburg, Germany) and T-SPOT.TB (T-SPOT, Oxford Immunotec; Oxford, UK), and placed a tuberculin skin test (TST) using the Mantoux method. Valid QFT-GIT results were defined as positive (≥0.35 IU/mL), negative, or indeterminate based on manufacturer recommendations. Study procedures allowed an indeterminate QFT test to be rerun with the same blood sample. T-SPOT results were interpreted using U.S. definitions in which negative results are defined as ≤4 spots, positive results as ≥8 spots, and borderline results as 5–7 spots. For analyses, borderline T-SPOT results were grouped into the negative category. Valid TSTs results were read within 44–76 hours of placing the test by a healthcare worker trained to read TST results, based on concerns by study sites that the recommended interval of 48–72 hours was too strict. Positive results were defined as ≥5 millimeters (mm) for high-risk persons (including close contacts and persons with HIV infection) and ≥10 mm for all other participants [13].

Participants were eligible for the current study if at least one test result for LTBI was positive. Due to participants receiving three TB infection tests during enrollment (i.e., TST, QFT-GIT, T-SPOT) and the possibility of repeat testing, criteria were developed to determine which TB infection tests would be considered for study purposes. All three TB infection tests performed within 14 days of each other for a participant were considered a “set.” If a participant had more than one result from a type of TB infection test (i.e., TST, QFT-GIT, or T-SPOT) within the 14-day period, the test result performed closest to the enrollment date was used for study purposes. We excluded U.S.-born participants from analyses due to our primary research questions. Decisions to recommend LTBI treatment were at the discretion of clinic providers. The results from decisions to offer LTBI treatment and participant acceptance and completion of treatment were reported to CDC as determined by study site clinic providers and clinic-specific practices. Due to the possibility of a participant having more than one round of LTBI treatment, the most recent and most complete round of LTBI treatment was considered the main LTBI treatment. In the case that the most recent treatment was not the most complete, the most recent regimen was preferred.

Participant-reported (or parent/legal guardian for participants ≤17 years) demographics and medical history were collected at enrollment by using standardized instruments by trained study staff. TBESC sites used the following question proposed by the U.S Census, “How well do you speak English? Would you say you speak English: Very well, Well, Not well, Not at all.” Those who answered “very well” were interviewed in English unless they requested an interpreter. All other individuals were offered an interpreter in the language of their choice. The results from these language proficiency questions were not available to our study. Participants who declined an interpreter were interviewed in English. Non-U.S.–born participants who did not use an interpreter did not have their native language captured in the study database. Interpreter types were telephone-based trained interpreter, an in-person trained interpreter, or a bilingual study interviewer, based on availability and at study site discretion. Training as a medical interpreter was not required for bilingual study interviewers. Family members, friends or other patients could not be interpreters. Treatment regimen categories included daily isoniazid for 6 or 9 months, daily rifampin for 4 months, weekly isoniazid/rifapentine for 12 weeks, and all other regimens. Participants could indicate one or more racial/ethnic categories. For participants who chose Hispanic/Latino and any other racial category, we designated their race/ethnicity as Hispanic/Latino. Other combinations of racial categories were included in the “Other” category due to small sample sizes.

Statistical analysis

Descriptive statistics were used to examine participants lost to follow-up, enrollment variations by clinic, and participants included in the study. Chi square or Fisher’s statistics were used to compare groups. Our primary outcomes of interest were participants’ acceptance of LTBI treatment and successful completion of LTBI treatment. Our primary predictor of interest was whether the use of an interpreter was associated with the outcomes of interest. We also evaluated whether interpreter usage was associated with a decision to offer LTBI treatment and whether the type of interpreter was associated with study outcomes.

We assessed for associations between our predictors of interest and each of the three LTBI treatment outcomes (offered, accepted, and completed LTBI treatment) using multivariable logistic regression models with random intercepts (melogit command in Stata) to account for TBESC site clustering. The following covariates were assessed: use of an interpreter, age, gender, race/ethnicity, enrollment indication, time residing in the United States, World Health Organization (WHO) region of birth, level of education, housing status, HIV status, diabetes, TB infection test results (positive or negative), and LTBI treatment regimen. For each model, if a variable had >10% missing information (including “don’t know/refused”), then the variable was dropped, including T-SPOT results, Bacille Calmette-Guérin (BCG) vaccine status, refugee status, income, injection drug use, alcohol consumption, correctional facility, holding center, and long-term care facility. We assessed for multicollinearity between our independent variables using variance inflation factors and condition indices. A two-sided P-value ≤0.05 was considered significant. All statistical analyses were performed using StataSE 17 (StataCorp, College Station, TX).

Ethics approvals

All participants provided written informed consent. The study was approved by the CDC’s institutional review board (IRB) and the IRBs of Johns Hopkins University School of Medicine, University of Maryland, Maryland Department of Health, North Texas Regional, and Atrium Health. Study authors (YS, MN) had access to identifiable data from a single study site during the data collection period.

Results

TBESC enrolled 22,131 participants at 18 TBESC-affiliated sites, of whom 9,531 participants had at least one positive TB infection test result and no evidence of active TB (Fig 1). Of the 9,531 participants diagnosed with LTBI, 8,761 were non-U.S.–born (91.9%) and included in our analyses, among whom 6,272 (71.6%) used an interpreter and 2,489 (28.4%) had their interview conducted in English (Table 1). Interpreter use varied by enrollment site with the highest at DeKalb County, Georgia (26.0%) and the lowest at Florida Department of Health—Gainesville (0.1%) and Montgomery County in Maryland (0.1%) (S2 Table). Among participants who used an interpreter, 2,248 (35.8%) used an in-person interpreter, 1,873 (29.9%) used a telephonic interpreter, and 2,151 (34.3%) used a bilingual member of the study staff (S3 Table). The five most common countries of origin were Myanmar (1,492, 17.0%), the Philippines (1,206, 13.8%), Bhutan (806, 9.2%), Mexico (522, 6.0%), and Somalia (388, 4.4%) (Table 1). Among participants who used an interpreter, the three most frequent languages were Burmese (n = 1,405, 22.4%), Spanish (n = 1,123, 17.9%) and Nepali (1,087, 17.3%). From the time that non-U.S.–born participants were screened for LTBI to completion of treatment, we found that there were losses at each stage of the cascade: 4,158 of 8,761 were offered LTBI treatment (47.5%), 3,789 of 4158 accepted treatment (91.1%) and 2,990 of 3789 completed treatment (78.9%) (Fig 1). Among non-U.S.–born participants with at least one positive LTBI test result, 2990 out of 8761 (34.1%) completed LTBI treatment.

Fig 1. Participants enrolled from July 20, 2012, to May 5, 2017.

Fig 1

Table 1. Characteristics of non-U.S.–born Tuberculosis Epidemiologic Studies Consortium participants by interview language during initial interview to determine eligibility for treatment of latent tuberculosis infection.

Characteristic Non-U.S.–born persons
Total
N = 8,761 (100%)
Interview in English
N = 2,489 (28.4%)
Interview in language other than English
N = 6,272 (71.6%)
Age in years
Mean age: 35.68
Range: [1, 97]
No. % No. % No. %
 0–14 1,015 11.6% 209 8.4% 806 12.9
 15–24 1,420 16.2% 454 18.2% 966 15.4%
 25–44 3,990 45.5% 1,067 42.9% 2,923 46.6%
 45–64 1,953 22.3% 664 26.7% 1,289 20.6%
 ≥65 383 4.4% 95 3.8% 288 4.6%
Gender
 Women 4,122 47.1% 1,188 47.7% 2,934 46.8%
 Men 4,636 52.9% 1,300 52.2% 3,336 53.2%
 Transgender1 3 0.0% 1 0.0% 2 0.0%
Race/Ethnicity
 Asian 3,311 37.8% 982 39.5% 2,329 37.1%
 Black/African American 1,333 15.2% 433 17.4% 900 14.4%
 Hispanic/Latino 1,053 12.0% 202 8.1% 851 13.6%
 White 318 3.6% 104 4.2% 214 3.4%
 Pacific Islander 174 2.0% 143 5.8% 31 0.5%
 Native American2 4 0.1% 2 0.1% 2 0.0%
 Other 2,047 23.4% 482 19.4% 1,565 25.0%
 Unknown 521 6.0% 141 5.7% 380 6.1%
Enrollment Reason
 Close contact 708 8.1% 365 14.7% 343 5.5%
 Non-U.S.–born 7,632 87.1% 2,012 80.8% 5,620 89.6%
 Member of a group with local LTBI prevalence ≥25%3 358 4.1% 69 2.8% 289 4.6%
 Spent at least 30 days in a high-risk country in the last 5 years4 27 0.3% 22 0.9% 5 0.1%
 HIV positive 36 0.4% 21 0.8% 15 0.2%
Time since arrival to the US
 Years (med, IQR) 8,719 0.2 (0.1–1.5) 2,473 0.62 (0.1–8.4) 6,246 0.1 (0.1–0.3)
 <5 years 7,120 81.3% 1,667 67.0% 5,453 81.3%
 ≥5 years 1,641 18.7% 822 33.0% 819 13.1%
HIV infection
 Yes 92 1.1% 43 1.7% 54 0.9%
 No 8,601 98.2% 2,432 97.7% 6,169 98.4%
 Don’t know/refused 68 0.8% 27 0.9% 54 0.9%
Diabetes mellitus
 Yes 424 4.8% 161 6.5% 263 4.2%
 No 8,270 94.4% 2,308 92.7% 5,962 95.1%
 Don’t Know/refused 67 0.8% 20 0.8% 47 0.8%
Experiencing homelessness
 Yes 142 1.6% 66 2.7% 76 1.2%
 No 8598 98.1% 2415 97.0% 6183 98.6%
 Don’t know/refused 21 0.2% 8 0.3% 13 0.2%
Injection drug use (n = 217)
 Yes 6 0.1% 4 0.2% 2 0.0%
 No 210 2.4% 101 4.1% 109 1.7%
 Don’t know/refused 1 0.0% 0 0.0% 1 0.0%
Consumption of 4 or more drinks containing alcohol (n = 2655)
 Never 1,546 17.6% 625 25.1% 921 14.7%
 Once a month or less 733 8.4% 268 10.8% 465 7.4%
 2–3 times a month 146 1.7% 57 2.3% 89 1.4%
 Once per week 102 1.2% 28 1.1% 74 1.2%
 2–3 times a week 57 0.7% 15 0.6% 42 0.7%
 4 or more times a week 26 0.3% 6 0.2% 20 0.3%
 Don’t Know/refused 45 0.5% 15 0.6% 30 0.5%
Correctional facility5
 Yes 312 3.6% 64 2.6% 248 4.0%
 No 7738 88.3% 2283 91.7% 5455 87.0%
 Don’t know/refused 9 0.1% 4 0.2% 5 0.1%
 Missing 702 8.0% 138 5.5% 546 9.0%
Holding Center6
 Yes 2,381 27.2% 141 5.7% 2,240 35.7%
 No 6335 72.3% 2321 93.3% 4014 64.0%
 Don’t know/refused 45 0.5% 27 1.1% 18 0.3%
Long-term care facility
 Yes 307 3.5% 190 7.6% 117 1.9%
 No 8440 96.3% 2288 91.9% 6152 98.1%
 Don’t know/refused 14 0.2% 11 0.4% 3 0.1%
Country of birth (5 most common)
 Myanmar 1,492 17.0% 23 0.9% 1,469 23.4%
 Philippines 1,206 13.8% 967 38.9% 239 3.8%
 Bhutan 806 9.2% 12 0.5% 794 12.7%
 Mexico 522 6.0% 100 4.0% 422 6.7%
 Somalia 388 4.4% 46 1.9% 342 5.5%
Region of birth country
 Africa 906 10.3% 259 10.4% 647 10.3%
 America 1,730 19.8% 442 17.8% 1,288 20.5%
 Europe 98 1.1% 46 1.9% 52 0.8%
 Mediterranean 1,049 12.0% 192 7.7% 857 13.7%
 Pacific 2,154 24.6% 1,357 54.5% 797 12.7%
 Southeast Asia 2,824 32.3% 193 7.8% 2,631 42.0%
Education
 No schooling 1,046 11.9% 25 1.0% 1,021 16.3%
 Eighth grade or less 2,642 30.2% 151 6.1% 2,491 39.7%
 Some high school 1,270 14.5% 242 9.7% 1,028 16.4%
 High school graduate or GED 1,604 18.3% 567 22.8% 1,037 16.5%
 Trade school or associates degree 186 2.1% 126 5.1% 60 1.0%
 Some university/college 730 8.3% 508 20.4% 222 3.5%
 University/college graduate 1,005 11.5% 659 26.5% 346 5.5%
 Postgraduate schooling 239 2.7% 202 8.1% 37 0.6%
 Other 7 0.1% 0 0.0% 7 0.1%
 Don’t know/refused 32 0.4% 9 0.4% 23 0.4%
LTBI Treatment regimen offered
 6- or 9- months isoniazid 700 8.0% 232 9.3% 468 7.5%
 4 months rifampin 1,697 19.4% 382 15.3% 1,315 21.0%
 12 weeks- weekly doses isoniazid/rifapentine 885 10.1% 166 6.7% 719 11.5%
 Other7 875 10.0% 108 4.3% 767 12.2%
LTBI Treatment regimen received
 6- or 9-months isoniazid 1,152 13.1% 249 10.0% 903 14.4%
 4 months rifampin 1,943 22.2% 319 12.8% 1,624 25.9%
 12 weeks- weekly doses isoniazid/rifapentine 484 5.5% 115 4.6% 369 5.9%
 Other 210 2.4% 71 2.9% 139 2.2%
Offered LTBI treatment
 Yes 4,158 47.5% 889 35.7% 3,269 52.1%
 No 4,525 51.6% 1,571 63.1% 2,954 47.1%
 Missing 78 0.9% 29 1.2% 49 0.8%
Accepted LTBI treatment
 Yes 3,789 91.1% 754 30.3% 3,035 48.4%
 No 369 8.9% 135 5.4% 234 3.7%
 Missing 0 0.0% 0 0.0% 0 0.0%
Completed LTBI treatment
 Yes 2,990 78.9% 575 23.1% 2,415 38.5%
 No 793 20.9% 177 7.1% 616 9.8%
 Missing 6 0.2% 2 0.1% 4 0.1%
Tuberculin Skin Test8
 Positive 7,822 89.3% 2,179 87.5% 5,643 90.0%
 Negative 864 9.9% 284 11.4% 580 9.2%
QuantiFERON-TB Gold In-Tube
 Positive 4,634 52.9% 1,297 52.1% 3,337 53.2%
 Negative 4,052 46.3% 1,169 47.0% 2,883 46.0%
T-SPOT.TB Test
 Positive 3,610 41.5% 932 37.9% 2,678 43.0%
 Negative 4,128 46.8% 1,177 46.9% 2,951 46.8%
 Borderline 547 6.2% 152 6.1% 395 6.3%

1Transgender participants were dropped from models due to other missing values

2Native American participants were dropped from models due to missing values

3Populations with a prevalence of LTBI ≥ 25% varied by site (e.g., individuals experiencing homelessness or have a specific medical condition)

4Refer to supplemental S1 Table for a list of high-risk countries

5Correctional facility such as prison or jail

6Holding center such as refugee camp or refugee detention

7Other regimens included: Ethambutol, Pyrazinamide, Levofloxacin, Moxifloxacin, Isoniazid/Rifampin

8Tuberculin skin test measured in millimeters of induration with positivity determined by LTBI risk (see Methods)

There was no association between use of an interpreter and a clinician’s decision to offer LTBI treatment in a multivariable model (S4 Table). Compared to participants whose enrollment indication was contact investigation, all other enrollment indications had lower odds of being offered treatment. In comparison to Asian participants, participants who identified as Pacific Islander persons had lower odds of being offered treatment (adjusted odds ratio [aOR] 0.64, 95% confidence interval [CI] 0.41–1.0). Participants who were experiencing homelessness also had lower odds of being offered treatment (aOR 0.41, 95% CI 0.26–0.65). Additional characteristics associated with decreased odds of treatment offer included longer time since U.S. entry and birthplace in the European and Pacific regions.

Participants who used an interpreter had greater odds of accepting LTBI treatment (aOR 1.66, 95% CI 1.18–2.33) (Table 2). Factors associated with lower odds of accepting LTBI treatment included Black race (aOR 0.54, 95% CI 0.31–0.95), Hispanic/Latino ethnicity (aOR 0.31, 95% CI 0.13–0.73) or “other” race (aOR 0.65, 95% CI 0.42–1.00), having diabetes (aOR 0.62, 95% CI 0.39–0.98), and attaining postgraduate-level education (aOR 0.33, 95% CI 0.16–0.69). Compared to the African region, participants born in the European and Pacific regions had lower odds of accepting treatment (aOR 0.18, 95% CI 0.06–0.54 and aOR 0.37, 95% CI 0.18–0.74, respectively). Participants living with HIV had greater odds of accepting treatment (aOR 8.03, 95% CI 0.93–69.66). Accepted treatment regimens were 4 months of rifampin (22.2%), 12 weeks of isoniazid/rifapentine (5.5%), 6 or 9 months of isoniazid (13.1%) and “Other” treatments (2.4%).

Table 2. Adjusted odds ratios for acceptance of LTBI treatment by use of an interpreter.

N = 3,973.

Characteristics Adjusted odds Ratio 95% confidence interval p-value
Interpreter 1.66 1.18–2.33 0.004
Time in the US (years) 1.02 1.00–1.05 0.07
Gender
 Women reference
 Men 0.98 0.77–1.26 0.90
Enrollment reason 1
 Close contact reference
 Non-U.S.–born 0.61 0.36–1.03 0.06
 Member of group with local LTBI prevalence2 ≥25% 0.60 0.17–2.09 0.42
 HIV infection 0.36 0.01–8.69 0.53
Age (Years) 0.98 0.97–0.99 <0.001
Race/ethnicity
 Asian reference
 Black/African American 0.54 0.31–0.95 0.03
 Hispanic/Latino 0.31 0.13–0.73 0.007
 White 0.60 0.30–1.17 0.13
 Pacific Islander 6.79 0.88–52.62 0.07
 Other 0.65 0.42–1.00 0.05
 Unknown 1.02 0.47–2.24 0.96
Region of birth country
 Africa reference
 America 1.21 0.56–2.61 0.63
 Europe 0.18 0.06–0.54 0.002
 Mediterranean 0.65 0.41–1.02 0.06
 Pacific 0.37 0.18–0.74 0.005
 Southeast Asia 0.91 0.51–1.64 0.77
Education
 No schooling reference
 Eighth grade or less 1.18 0.77–1.81 0.44
 Some high school 1.02 0.62–1.67 0.94
 High school graduate or GED 0.94 0.58–1.53 0.81
 Trade school or associates degree 0.87 0.38–1.98 0.71
 Some university/college 0.74 0.41–1.32 0.31
 University/college graduate 0.68 0.41–1.15 0.15
 Postgraduate schooling 0.33 0.16–0.69 0.003
Housing Status 3.00 0.60–15.02 0.18
 Housed reference
 Experiencing homelessness 3.00 0.60–15.02 0.18
HIV
 HIV uninfected reference
 Living with HIV infection 8.03 0.93–69.66 0.06
Diabetes
 Without diabetes reference
 Living with diabetes 0.62 0.39–0.98 0.04
LTBI treatment accepted
 6- or 9- months isoniazid reference
 4 months rifampin 1.21 0.74–1.96 0.45
 12 weeks- weekly doses isoniazid/rifapentine 1.61 0.97–2.69 0.07
 Other3 0.90 0.48–1.71 0.75
Tuberculin Skin Test (TST)
 TST Negative reference
 TST Positive 0.99 0.68–1.44 0.95
QuantiFERON-TB Gold In-Tube 4
 Negative QuantiFERON-TB reference
 Positive QuantiFERON-TB 1.35 0.97–1.88 0.08

1The variable “Spent at least 30 days in a high-risk country in the last 5 years” was dropped from the model due to other missing values

2Populations with a prevalence of LTBI ≥ 25% varied by site (e.g., individuals experiencing homelessness or have a specific medical condition)

3Other regimens included: Ethambutol, Pyrazinamide, Levofloxacin, Moxifloxacin, Isoniazid/Rifampin

4T-SPOT.TB test excluded due to >10% missing data

Interpreter usage was not associated with greater treatment completion (aOR 1.29, 95% CI 0.98–1.70) (Table 3). Participants who were born in the Mediterranean WHO region had lesser odds of completing treatment (aOR 0.49, 95% CI 0.35–0.70) compared to participants born in the African region. Participants who were experiencing homelessness had lower odds of completing treatment (aOR 0.49, 95% CI 0.24–0.99). Compared to treatment with 6 or 9 months of isoniazid, participants treated with all other regimens had greater odds of completing treatment.

Table 3. Adjusted odds ratios for completion of LTBI treatment by use of an interpreter.

1 N = 3,626.

Characteristics Adjusted Odds Ratio 95% Confidence Interval p-value
Interpreter 1.28 0.97–1.69 0.08
Time in the US (years) 1.01 0.99–1.03 0.42
Gender
 Women reference
 Men 1.14 0.95–1.35 0.15
Enrollment reason 2
 Close contact reference
 Non-U.S.–born 0.94 0.66–1.33 0.72
 Member of group with local LTBI prevalence ≥25%3 1.30 0.59–2.83 0.51
 HIV positive 0.52 0.13–2.13 0.37
Age (years) 1.00 0.99–1.00 0.21
Race/ethnicity
 Asian reference
 Black/African American 0.76 0.51–1.14 0.19
 Hispanic/Latino 0.71 0.41–1.22 0.21
 White 0.64 0.38–1.08 0.10
 Pacific Islander 0.56 0.20–1.59 0.28
 Other 0.91 0.69–1.21 0.52
 Unknown 0.82 0.52–1.30 0.40
Region of birth country
 Africa reference
 America 0.61 0.36–1.04 0.07
 Europe 0.33 0.09–1.21 0.10
 Mediterranean 0.49 0.35–0.70 <0.001
 Pacific 0.70 0.41–1.21 0.20
 Southeast Asia 1.05 0.69–1.62 0.81
Education 4
 No schooling reference
 Eighth grade or less 1.02 0.78–1.35 0.87
 Some high school 1.22 0.88–1.69 0.24
 High school graduate or GED 1.34 0.96–1.87 0.09
 Trade school or associate degree 1.58 0.81–3.08 0.18
 Some university/college 1.49 0.95–2.33 0.08
 University/college graduate 1.52 1.01–2.30 0.04
 Postgraduate schooling 1.92 0.81–4.52 0.14
 Don’t know/refused 0.46 0.14–1.47 0.19
Housing status
 Housed reference
 Experiencing homelessness 0.49 0.24–0.98 0.045
HIV
 HIV uninfected reference
 Living with HIV infection 1.49 0.62–3.60 0.37
Diabetes
 Without diabetes reference
 Living with diabetes 1.04 0.69–1.57 0.85
LTBI treatment initially accepted
 6- or 9-months isoniazid reference
 4 months rifampin 1.34 1.07–1.70 0.01
 12 weeks- weekly doses isoniazid/rifapentine 2.77 1.95–3.93 <0.001
 Other regimens 1.73 1.11–2.70 0.02
Tuberculin Skin Test 1.21 0.92–1.60 0.17
QuantiFERON-TB Gold In-Tube 1.15 0.92–1.44 0.21

1T-SPOT.TB test excluded due to >10% missing data

2 Participants enrolled due to having spent at least 30 days in a high-risk country were removed from this model due to a small number (n = 6)

3Populations with a prevalence of LTBI ≥ 25% varied by site (e.g., individuals experiencing homelessness or have a specific medical condition)

4Participants enrolled with an education level of “other” were removed from this model due to a small number (n = 4)

We evaluated the effects of interpreter type on treatment outcomes. All interpreter types were trained in medical interpretation and included telephone-based, in-person, or bilingual study interviewers (S4 Table). Interpreter type was not associated with a decision to offer, accept, or complete LTBI treatment (S5S7 Tables, respectively).

Discussion

In a large multisite study, we evaluated the effect of the use of interpreters on LTBI treatment offer, acceptance, and completion in non-U.S.–born persons. We found that the use of a trained medical interpreter was associated with a 66% increased odds of treatment acceptance. There was no statistically significant association between interpreter use and a decision to offer treatment or treatment completion. Many non-U.S.–born persons are at increased risk for both LTBI and progression to TB. Among non-U.S.–born persons who have limited English proficiency, their understanding of LTBI might be affected by whether they receive patient education about TB infection in English or in their preferred language through the use of an interpreter.

Consistent with prior research [4], we found that the largest losses in the LTBI treatment continuum (over 50%) occurred at the step of offering treatment, which was at clinicians’ discretion.. Participants who were enrolled on the basis of non-U.S. birth, HIV infection or local LTBI prevalence of at least 25% had lesser odds of being offered LTBI treatment than close contacts to a TB case. In order to improve LTBI care continuum outcomes, reasons for these differences should be investigated. Possibly reflecting health disparities, participants who identified as Pacific Islander persons and persons experiencing homelessness had lower odds of being offered LTBI treatment. For treatment acceptance, it is concerning that persons whose race/ethnicities were Black, Latino, or “other”, and those with diabetes were less likely to accept LTBI treatment. The finding that higher levels of education were associated with lower treatment acceptance was unexpected. We hypothesize that this may be due to misconceptions about test results in the setting of BCG vaccination or about TB occurrence in persons with higher socioeconomic status. Lack of housing was independently associated with lower likelihood of treatment completion, underscoring the need to develop interventions specific to persons who experience homelessness. Further investigations into these associations are warranted. Similar to other studies [1416], shorter course rifamycin-based LTBI treatment regimens are associated with decreased losses across the care continuum.

There was no association between the type of interpreter and LTBI outcomes. All three interpreter types were effective in increasing treatment acceptance. In-person interpreters may not be available at all clinical sites of practice, and our findings should provide reassurance around the effect of telephone-based interpretation. Although bilingual study interviewers are a type that is unique to study settings, there may be similarities to bilingual clinicians, and this deserves further investigation.

There are several limitations to this study. TBESC sites used a standard question to assess English proficiency and offered interpreters on the basis of the response. Participants who answered less proficient than “very well” could decline use of an interpreter and conduct the interview in English. As we did not have access to the responses to English proficiency, we could not evaluate differences in interpreter impact by objective measures of English proficiency. We were unable to further explore differences in LTBI outcomes by language as the language of participants were collected only for those who accepted an interpreter. A trained interpreter may not have been available for the preferred language of participants, resulting in a situation in which participants may have still been disadvantaged due to limited language proficiency. Observed associations between variables and our outcomes of interest may have been driven by site-specific differences. To address this, we used random intercept models to adjust for enrollment site. Our study did not address earlier steps in the LTBI treatment cascade, such as a decision to test and communication of the results to patients, where the greatest losses may occur [17].

In summary, our study found that non-U.S.–born people with limited English proficiency may benefit from the use of an interpreter regardless of the interpreter method (bilingual interpreter, in-person, by telephone). We identified a number of possible health inequities associated with ethnicity and housing status that should be investigated further. Finally, clinician offering of LTBI treatment appeared to be suboptimal in our study, regardless of whether an interpreter was used. Use of an interpreter, in addition to shorter course regimens for LTBI treatment, increases treatment completion rates among non-U.S.–born persons and is an important intervention for addressing health disparities among persons with limited English proficiency.

Tuberculosis Epidemiologic Studies Consortium

California Department of Public Health, Richmond Jennifer Flood, Lisa Pascopella (includes San Francisco Department of Public Health, Julie Higashi; County of San Diego Health and Human Services Agency, Kathleen Moser, Marisa Moore [CDC]; and University of California San Diego Antiviral Research Center, Richard Garfein, Constance Benson); Denver (CO) Health and Hospital Authority Robert Belknap, Randall Reves; Duke University (Durham, NC) Jason Stout (includes Carolinas Medical Center [Charlotte, NC], Amina Ahmed; Vanderbilt University Medical Center [Nashville, TN], Timothy Sterling, April Pettit; Wake County Human Services [Raleigh, NC], Jason Stout); Emory University (Atlanta) Henry M Blumberg (includes DeKalb County Board of Health, Alawode Oladele); University of Florida (Gainesville) Michael Lauzardo, Marie Nancy Séraphin; Hawaii Department of Health (Honolulu) Richard Brostrom; Maricopa County Department of Public Health (Phoenix, AZ) Renuka Khurana; Maryland Department of Health (Baltimore), Wendy Cronin, Susan Dorman; Public Health—Seattle and King County Masahiro Narita, David Horne; University of North Texas Health Science Center (Fort Worth) Thaddeus Miller.

Supporting information

S1 Table. Countries with high rates of tuberculosis (>100 cases per 100,000 population).

(DOCX)

pone.0298628.s001.docx (23.8KB, docx)
S2 Table. The number of non-U.S.–born participants enrolled at different sites by interview language, English or other than English.

(DOCX)

pone.0298628.s002.docx (15.7KB, docx)
S3 Table. Characteristics of TBESC participants who used an interpreter by interpreter type.

(DOCX)

pone.0298628.s003.docx (56.6KB, docx)
S4 Table. Adjusted odds ratios for the offer of LTBI treatment by use of an interpreter.

N = 8,402.

(DOCX)

pone.0298628.s004.docx (17.7KB, docx)
S5 Table. Adjusted* odds ratios for the offer of LTBI treatment by interpreter type.

N = 6,027.

(DOCX)

pone.0298628.s005.docx (18.9KB, docx)
S6 Table. Adjusted* odds ratios for acceptance of LTBI treatment by interpreter type.

N = 3,114.

(DOCX)

pone.0298628.s006.docx (20.4KB, docx)
S7 Table. Adjusted* odds ratio for completion of LTBI treatment by interpreter type.

N = 2,913.

(DOCX)

pone.0298628.s007.docx (20.5KB, docx)

Acknowledgments

The findings and conclusions in this report are those of the authors and do not necessarily represent official CDC positions.

We are grateful for the assistance of the CDC headquarters TBESC team: Gabrielle Fanning-Dowdell, Thara Venkatappa, Rose Punnoose, Matthew Whipple, Kathryn Winglee, and Yanjue Wu. We also acknowledge the contributions of the previous TBESC project officer, Denise Garrett, and branch chief, Tom Navin. We acknowledge the assistance of the TBESC site project coordinators: Katya Salcedo, Laura Romo, Christine Kozik, Carlos Vera, Juanita Lovato, Laura Farrow, Colleen Traverse Kristian Atchley, Fernanda Maruri, Kursten Lyon, Debra Turner, Nubia Flores, Jane Tapia, Livia Sura, Joanne C Li, Marie McMillan, Stephanie Reynolds-Bigby, Angela Largen, Aurimar Ayala, Elizabeth Munk, Gina Maltas, Yoseph Sorri, Kenji Matsumoto, Amy Board, and James Akkidas.

Data Availability

The data is now publicly available at the CDC's website: https://data.cdc.gov/National-Center-for-HIV-Viral-Hepatitis-STD-and-TB/Tuberculosis-Epidemiologic-Studies-Consortium-TBES/5hpj-p74g/about_data.

Funding Statement

This work was supported by a contract with the Centers for Disease Control and Prevention. All authors report no potential conflicts of interest.

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Decision Letter 0

Lisa Kawatsu

26 Dec 2023

PONE-D-23-18821Interpreter usage and associations with latent tuberculosis infection treatment outcomes in the USA among non-U.S.–born persons, 2012–2017PLOS ONE

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Reviewer #1: The article presents the evaluation of the use of an interpreter and its effect on LTBI treatment offer, acceptance and completion in non-US born individuals. The study uses a subpopulation of non-U.S.–born who participated in a previously published study that assessed LTBI diagnostics and their predictive capabilities to detect progression of those with LTBI to TB disease. This is a very important topic and the manuscript presents results that are of interest to the scientific community, however, the authors must first address a number of issues.

1. Major: The tittle refers to "treatment outcomes" however, I think this tittle may be misleading because the study does not address LTBI treatment outcomes as they may be understood e.g., disease Vs no disease or cured Vs no cured. As the authors mention in line 296-297 of the discussion section "effect of the use of interpreters on LTBI treatment offer, acceptance, and completion" that's what they evaluated. The tittle should be modified accordingly. This should also be modified in line 30 of the abstract.

2. Minor: abstract lines 34-38, it is not clear what is a primary outcome and a secondary outcome.

3. Minor: line 79 of the introduction, please include a reference to support the statement "LTBI treatment is highly effective in preventing progression of LTBI to TB disease"

4. Major: lines 106-108, Clarify what the primary and secondary outcomes are: Primary outcome seems to be treatment acceptance and completion. Secondary outcomes: association with clinicians decision to offer treatment? Association with treatment outcomes? If that's the primary outcome, as mentioned in point 1, the title of the manuscript should be changed "associations with latent tuberculosis infection treatment acceptance and completion" In lines 181-182 and 184-185 mentions that the primary outcome was acceptance and completion.

5. Minor: line 109, replace "type associated with" for "type was associated with"

6. Minor: line 125-126, why was a hierarchy of enrollment reasons necessary? There's no further mention to this or enough explanation on why it was important/needed.

7. Minor: lines 149-152 ”If a participant had more 150 than one TST, QFT-GIT, or T-SPOT test within 14 days, the TB infection test(s) where all three tests were performed closest to the enrollment date were defined as the “main set” for study 152 purposes" this is confusing and hard to understand, could you please clarify this.

8. Major: line 154-155, how were these outcomes defined and ascertained? Describe it briefly.

9. Major: line 225, "Among non-U.S.–born participants with at least one positive LTBI test result, 34.1% completed LTBI treatment" This is confusing, 2990 out of 3789 completed treatment (78.9%), but the next line refers to 34.1% completing treatment, what's the number? And what do these participants refer to?

10. Major: Table 2, how can the total N of the model presented in the table be 3,973 if in table 1 there is information on homelessness for only 163 participants? Same for other variables e.g., injecting drug use. If what is presented in table 2 is the result of a multivariate analysis and there are missing for those variables, then they will be automatically dropped by the model. I would recommend to add the N for each variable if this is an univariate analysis, for a multivariate analysis the N will equal the number in the variable with the lower number of observations. Same for table 3.

11. Major: Table 2, for variable enrollement reason, the category Non-US born should have not been included in the model because all participants included in the analysis are non-US born, so this is a perfect predictor. Same for table 3.

12. Minor: Table 2 and 3, were variables interpreter, time in US, age, HIV, Diabetes and TST included in the model as categorical variables? If so, what's the reference? For all other categories a reference is provided.

13. Major: I am concerned with the inclusion of categorical variables with more than 3 categories in these models with small sample sizes, these type of variables are normally very problematic, could you provide any information on model fit?

14. Minor: line 302, "their understanding of LTBI might be affected by whether their receive patient" should the last their be replaced by they?

Reviewer #2: Thanks for the opportunity to review this manuscript, which considers the association between interpreter use and LTBI treatment outcomes in the United States. This is an interesting manuscript dealing with an important programmatic question, and I’m pleased to see the authors considering this valuable work.

It is well-recognized that the most substantial losses in the LTBI cascade of care arise early, and investigations into factors affecting treatment uptake are highly important for programs to consider. The role of interpreters, particularly in a setting such as this where there is considerable ethnic and language diversity in the cohort, is crucial and understudied, so this work is well-positioned and useful.

In addition to the primary findings, I also note that other characteristics associated with treatment outcomes are reported. These include factors such as homelessness, which is associated with lower treatment outcomes. These are generally in keeping with existing published data on treatment outcomes and so are in themselves less novel, but helpful for contextualising the cohort here.

Comments

1. The finding that interpreter type was not associated with treatment acceptance is interesting, and probably reassuring with regards to available options in different settings. The authors say that all interpreter types were trained rather than informal; can I clarify whether this is also true for the bilingual clinician interviewers (type 3)? That is, was this group trained/accredited in some way as an interpreter, or should this be taken just to mean that they were both trained as interviewers and also bilingual.

2. Table 1 includes several fields with very small numbers, including a single transgender individual and small numbers of people using intravenous drugs in some fields. It would be common practice to redact such small numbers to avoid potential identification of individuals for ethical reasons, which the authors/editors may consider here.

3. It’s interesting to see that duration of residence in the US was positively associated with LTBI treatment acceptance. This may be intuitive, and associated with other factors allowing prioritisation of LTBI treatment later after migration, but is also associated with decreased risk of reactivation – so there may be some perverse incentives at play worth noting where those at greater risk of future TB are less likely to accept therapy.

4. The steady and linear association between increasing education and decreasing acceptance of LTBI treatment is striking here, and I think worth commenting on further in the text. How would the authors understand this phenomenon?

5. The authors note that the study is limited by lack of objective data on English proficiency. This can’t be changed and is reasonably acknowledged in the text already, but I think a further comment about the human rights need to ensure adequate interpreting services are at least available and accessible for adequate provision of clinical services would be appropriate, perhaps with reference to the existing literature on use of interpreting services in TB programs.

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PLoS One. 2024 Apr 16;19(4):e0298628. doi: 10.1371/journal.pone.0298628.r002

Author response to Decision Letter 0


8 Jan 2024

Reviewers' comments

Reviewer #1:

The article presents the evaluation of the use of an interpreter and its effect on LTBI treatment offer, acceptance and completion in non-US born individuals. The study uses a subpopulation of non-U.S.–born who participated in a previously published study that assessed LTBI diagnostics and their predictive capabilities to detect progression of those with LTBI to TB disease. This is a very important topic and the manuscript presents results that are of interest to the scientific community, however, the authors must first address a number of issues.

Thank you for your supportive comments and helpful critiques.

1. Major: The title refers to "treatment outcomes" however, I think this title may be misleading because the study does not address LTBI treatment outcomes as they may be understood e.g., disease Vs no disease or cured Vs no cured. As the authors mention in line 296-297 of the discussion section "effect of the use of interpreters on LTBI treatment offer, acceptance, and completion" that's what they evaluated. The title should be modified accordingly. This should also be modified in line 30 of the abstract.

We appreciate this comment. We have changed the title to the following and edited the abstract:

“Interpreter usage and associations with latent tuberculosis infection treatment acceptance and completion in the USA among non-U.S.–born persons, 2012–2017”.

2. Minor: abstract lines 34-38, it is not clear what is a primary outcome and a secondary outcome.

Thank you. We have edited the abstract to include the following sentence, “Our primary outcomes were whether use of an interpreter was associated with LTBI treatment acceptance and completion.”

3. Minor: line 79 of the introduction, please include a reference to support the statement "LTBI treatment is highly effective in preventing progression of LTBI to TB disease"

We have added the following reference in support of this statement:

Zenner D, Beer N, Harris RJ, Lipman MC, Stagg HR, van der Werf MJ. Treatment of Latent Tuberculosis Infection: An Updated Network Meta-analysis. Ann Intern Med. 2017 Aug 15;167(4):248-255. PMID: 28761946.

4. Major: lines 106-108, Clarify what the primary and secondary outcomes are: Primary outcome seems to be treatment acceptance and completion. Secondary outcomes: association with clinicians decision to offer treatment? Association with treatment outcomes? If that's the primary outcome, as mentioned in point 1, the title of the manuscript should be changed "associations with latent tuberculosis infection treatment acceptance and completion" In lines 181-182 and 184-185 mentions that the primary outcome was acceptance and completion.

We have clarified our primary outcomes in the concluding paragraph of the Introduction with the following, “Given the importance of addressing healthcare inequities and improving outcomes across the LTBI care continuum in non-U.S.–born persons, we investigated associations between the use of trained medical interpreters and LTBI treatment acceptance and completion in a TBESC study as our primary outcomes.”

We have also edited the manuscript title (please see #1, above).

5. Minor: line 109, replace "type associated with" for "type was associated with"

Thank you for catching this error. We have made this edit.

6. Minor: line 125-126, why was a hierarchy of enrollment reasons necessary? There's no further mention to this or enough explanation on why it was important/needed.

Great comment. As “enrollment reason” is a variable included in our regression models, we used this hierarchy to assign participants to a category. We have edited the cited sentence to the following, “For participants with more than one eligibility criterion, a hierarchy of enrollment reasons was established to assign a category to this variable in regression models: 1) close contact of person with infectious TB, 2) non-U.S.–born person from a high-risk country or recently arrived from medium risk country (Supplemental Table 1), 3) visitor of ≥30 days in a high-risk country during prior 5 years, 4) person belonging to a population with a LTBI prevalence ≥25%, and 5) person living with HIV.”

7. Minor: lines 149-152 ”If a participant had more 150 than one TST, QFT-GIT, or T-SPOT test within 14 days, the TB infection test(s) where all three tests were performed closest to the enrollment date were defined as the “main set” for study 152 purposes" this is confusing and hard to understand, could you please clarify this.

We have edited the sentence to the following, “If a participant had more than one result from a type of TB infection test (i.e., TST, QFT-GIT, or T-SPOT) within the 14-day period, the test result performed closest to the enrollment date was used for study purposes.”

8. Major: line 154-155, how were these outcomes defined and ascertained? Describe it briefly.

We have edited the sentence to the following, “The results from decisions to offer LTBI treatment and participant acceptance and completion of treatment were reported to CDC as determined by study site clinic providers and clinic-specific practices.”

9. Major: line 225, "Among non-U.S.–born participants with at least one positive LTBI test result, 34.1% completed LTBI treatment" This is confusing, 2990 out of 3789 completed treatment (78.9%), but the next line refers to 34.1% completing treatment, what's the number? And what do these participants refer to?

We have clarified this sentence, “Among non-U.S.–born participants with at least one positive LTBI test result, 2990 out of 8761 (34.1%) completed LTBI treatment.”

10. Major: Table 2, how can the total N of the model presented in the table be 3,973 if in table 1 there is information on homelessness for only 163 participants? Same for other variables e.g., injecting drug use. If what is presented in table 2 is the result of a multivariate analysis and there are missing for those variables, then they will be automatically dropped by the model. I would recommend to add the N for each variable if this is an univariate analysis, for a multivariate analysis the N will equal the number in the variable with the lower number of observations. Same for table 3.

We appreciate the opportunity to clarify the data. The housing status is known for 8740 participants. We did not include a Table 1 row for the 8598 housed participants. We have corrected this in Table 1 and added similar rows for correctional facility, holding center, and long-term care facility. For clarity we have added the “n” for injection drug use and alcohol consumption, both of which have high levels of missing data. Variables with high levels of missing data (e.g., injection drug) were not included in our models.

The ”N” values for Tables 2 and 3 are indicated in the Titles, 3973 and 3626, respectively.

11. Major: Table 2, for variable enrollment reason, the category Non-US born should have not been included in the model because all participants included in the analysis are non-US born, so this is a perfect predictor. Same for table 3.

This variable and its categories refer to the primary reason that the participant was enrolled into the TBESC study. This is addressed in our response to question 6, above.

12. Minor: Table 2 and 3, were variables interpreter, time in US, age, HIV, Diabetes and TST included in the model as categorical variables? If so, what's the reference? For all other categories a reference is provided.

Again, thank you. Time in U.S. and age are continuous variables. The reference for HIV is HIV-uninfected, for diabetes is being without diabetes and for TST positive is having a TST negative result. For these categorical variables, we have added rows to Tables 2 and 3 that clarify the reference categories.

13. Major: I am concerned with the inclusion of categorical variables with more than 3 categories in these models with small sample sizes, these type of variables are normally very problematic, could you provide any information on model fit?

We appreciate this rigorous suggestions. We reviewed the levels for each categorical variable included in our primary outcomes and identified two with small numbers of participants (<10). We found that in the treatment completion model (Table 3), primary enrollment reason of having spent at least 30 days in a high-risk country (n=6) and education level of “other” (n=4) had few participants. Rather than collapsing these categories into other unrelated categories, we have removed these participants, edited table 3 and included footnotes on the table to this effect.

14. Minor: line 302, "their understanding of LTBI might be affected by whether their receive patient" should the last their be replaced by they?

Thank you. We have made the suggested edit.

Reviewer #2

Thanks for the opportunity to review this manuscript, which considers the association between interpreter use and LTBI treatment outcomes in the United States. This is an interesting manuscript dealing with an important programmatic question, and I’m pleased to see the authors considering this valuable work. It is well-recognized that the most substantial losses in the LTBI cascade of care arise early, and investigations into factors affecting treatment uptake are highly important for programs to consider. The role of interpreters, particularly in a setting such as this where there is considerable ethnic and language diversity in the cohort, is crucial and understudied, so this work is well-positioned and useful.

We appreciate the Reviewer 2’s supportive words.

Comments

1. The finding that interpreter type was not associated with treatment acceptance is interesting, and probably reassuring with regards to available options in different settings. The authors say that all interpreter types were trained rather than informal; can I clarify whether this is also true for the bilingual clinician interviewers (type 3)? That is, was this group trained/accredited in some way as an interpreter, or should this be taken just to mean that they were both trained as interviewers and also bilingual.

Thank you for this question. Specific training as a medical interpreter was not required for bilingual clinician interviewers. We have added the following sentence to the Methods, “Training as a medical interpreter was not required for bilingual study interviewers.”

2. Table 1 includes several fields with very small numbers, including a single transgender individual and small numbers of people using intravenous drugs in some fields. It would be common practice to redact such small numbers to avoid potential identification of individuals for ethical reasons, which the authors/editors may consider here.

We appreciate the concern for identification of study participants. This manuscript was extensively reviewed by CDC who are comfortable with the presentation. This is due, in part, to the fact that the data will not be publicly shared until May, 2024, when a fully deidentified dataset will be made available.

3. It’s interesting to see that duration of residence in the US was positively associated with LTBI treatment acceptance. This may be intuitive and associated with other factors allowing prioritisation of LTBI treatment later after migration, but is also associated with decreased risk of reactivation – so there may be some perverse incentives at play worth noting where those at greater risk of future TB are less likely to accept therapy.

We agree with the Reviewer’s attention to this finding. However, we did not highlight it in the discussion because the association did not reach statistical significance (p-value 0.07) in multivariable analysis.

4. The steady and linear association between increasing education and decreasing acceptance of LTBI treatment is striking here, and I think worth commenting on further in the text. How would the authors understand this phenomenon?

We added the following to the Discussion, “The finding that higher levels of education were associated with lower treatment acceptance was unexpected. We hypothesize that this may be due to misconceptions about test results in the setting of BCG vaccination or about TB occurrence in persons with higher socioeconomic status.”

5. The authors note that the study is limited by lack of objective data on English proficiency. This can’t be changed and is reasonably acknowledged in the text already, but I think a further comment about the human rights need to ensure adequate interpreting services are at least available and accessible for adequate provision of clinical services would be appropriate, perhaps with reference to the existing literature on use of interpreting services in TB programs.

Thank you. We have edited the manuscript’s concluding sentence, “Use of an interpreter, in addition to shorter course regimens for LTBI treatment, increases treatment completion rates among non-U.S.–born persons and is an important intervention for addressing health disparities among persons with limited English proficiency.”

Again, thank you for the careful reviews and please do not hesitate to reach out to me with questions.

Attachment

Submitted filename: PLOS ONE reviewer response signed.docx

pone.0298628.s008.docx (62.8KB, docx)

Decision Letter 1

Lisa Kawatsu

29 Jan 2024

Interpreter usage and associations with latent tuberculosis infection treatment acceptance and completion in the USA among non-U.S.–born persons, 2012–2017

PONE-D-23-18821R1

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Acceptance letter

Lisa Kawatsu

1 Apr 2024

PONE-D-23-18821R1

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Countries with high rates of tuberculosis (>100 cases per 100,000 population).

    (DOCX)

    pone.0298628.s001.docx (23.8KB, docx)
    S2 Table. The number of non-U.S.–born participants enrolled at different sites by interview language, English or other than English.

    (DOCX)

    pone.0298628.s002.docx (15.7KB, docx)
    S3 Table. Characteristics of TBESC participants who used an interpreter by interpreter type.

    (DOCX)

    pone.0298628.s003.docx (56.6KB, docx)
    S4 Table. Adjusted odds ratios for the offer of LTBI treatment by use of an interpreter.

    N = 8,402.

    (DOCX)

    pone.0298628.s004.docx (17.7KB, docx)
    S5 Table. Adjusted* odds ratios for the offer of LTBI treatment by interpreter type.

    N = 6,027.

    (DOCX)

    pone.0298628.s005.docx (18.9KB, docx)
    S6 Table. Adjusted* odds ratios for acceptance of LTBI treatment by interpreter type.

    N = 3,114.

    (DOCX)

    pone.0298628.s006.docx (20.4KB, docx)
    S7 Table. Adjusted* odds ratio for completion of LTBI treatment by interpreter type.

    N = 2,913.

    (DOCX)

    pone.0298628.s007.docx (20.5KB, docx)
    Attachment

    Submitted filename: PLOS ONE reviewer response signed.docx

    pone.0298628.s008.docx (62.8KB, docx)

    Data Availability Statement

    The data is now publicly available at the CDC's website: https://data.cdc.gov/National-Center-for-HIV-Viral-Hepatitis-STD-and-TB/Tuberculosis-Epidemiologic-Studies-Consortium-TBES/5hpj-p74g/about_data.


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