Tuberculosis in United States-Bound Follow-to-Join Asylees, 2014–2019

ABSTRACT. Persons may seek asylum in the United States or at a U.S. port of entry. Principal asylees are those who are granted asylum status. Their spouse and unmarried children under 21 years of age may be granted asylum if accompanying, or following to join, the principal asylees. U.S.-bound follow-to-join asylees must undergo an overseas medical examination that includes tuberculosis (TB) screening. Culture-based overseas TB screening in U.S.-bound follow-to-join asylees has not been evaluated. We evaluated data from overseas TB screening in 19,088 arrivals of follow-to-join asylees during 2014–2019 and assessed data from their postarrival evaluation, which is recommended for those at risk for TB. Of 19,088 arrivals of follow-to-join asylees, 29 (152 cases/100,000 persons) met criteria for class B0 TB (recent completion of TB treatment overseas) and 340 (1,781 cases/100,000 persons) met criteria for class B1 pulmonary TB (chest radiograph/clinical symptoms suggestive of TB but negative sputum cultures overseas). Of 6,847 persons aged 2 to 14 years from countries with a WHO-estimated TB incidence of ≥20 cases/100,000 population/year, 408 (6.0%) were classified as class B2 latent TB infection (LTBI). Postarrival evaluations were completed in 44.8%, 51.5%, and 40.4% of persons with class B0 TB, class B1 TB, and class B2 LTBI, respectively. In conclusion, culture-based overseas TB screening in U.S.-bound follow-to-join asylees is effective in identifying those with TB (class B0 TB) or those at risk for TB (class B1 TB and class B2 LTBI). Completion of postarrival evaluation for newly arrived follow-to-join asylees was less frequent than that reported for immigrants and refugees.


INTRODUCTION
Asylees are persons who are unable or unwilling to return to their country of nationality because of persecution or a well-founded fear of persecution due to race, religion, nationality, membership in a particular social group, or political opinion. 1 Applicants may seek asylum in the United States or at a U.S. port of entry.Principal asylees are those who are granted asylum status in the United States.The spouse and unmarried children under the age of 21 who are listed on the principal asylee's application for asylum but not in their grant of asylum may obtain derivative asylum status. 2 Within 2 years of their grant of asylum, a principal asylee may petition for follow-to-join benefits for qualifying derivatives who may be located abroad or in the United States. 2 In 2019, 46,508 persons were granted asylum, of these, 13.5% (6,270)  were follow-to-join asylees located overseas and in the United States. 2 Tuberculosis (TB) is one of the most common causes of death from infectious diseases globally. 3In 2022, 72.9% of new TB cases reported in the United States occurred among non-U.S.-born persons. 4To reduce the importation of TB into the United States, an overseas medical examination that includes TB screening is required for U.S.-bound immigrants and refugees [5][6][7] and U.S.-bound follow-to-join asylees living abroad. 8Before 2007, a sputum smear-based algorithm was used in TB screening, but this algorithm could not identify smear-negative and culture-positive TB. 6 In 2007, the CDC developed a new screening algorithm to include mycobacterial culture for persons with a chest radiograph suggestive of TB and directly observed therapy for those diagnosed with TB disease. 7,9Implementation of the culture-based screening algorithm began in 2007 and was scaled up to all countries by 2013.Culture-based overseas TB screening has been found to be effective on finding and treating U.S.-bound immigrants and refugees with TB disease, 7 but its effectiveness in U.S.-bound follow-to-join asylees has not been assessed.We used data from CDC's Electronic Disease Notification (EDN) database to evaluate culture-based overseas TB screening in U.S.-bound follow-to-join asylees.

MATERIALS AND METHODS
Overseas TB screening.Tuberculosis screening is a major component of the mandatory medical examination for U.S.-bound immigrants and refugees [5][6][7] and U.S.-bound follow-to-join asylees. 8The overseas medical examination is performed by "panel physicians," licensed local physicians who are appointed by U.S. embassies and consulates. 10The CDC provides technical instructions and quality oversight for the examination.The culture-based algorithm, which is used in TB screening and treatment, requires all persons aged $ 15 years to have a chest radiograph and those aged 2 to 14 years in countries with a WHO-estimated TB incidence of $ 20 cases/100,000 population/year to undergo a tuberculin skin test (TST) or interferon-g release assay (IGRA) and, if positive, to have a chest radiograph. 7,9Since October 2013, panel physicians have been required to make the switch from analog to digital systems for chest radiographs.Prior to 2018, TST or IGRA was used with a test for latent TB infection (LTBI).Since 2018, IGRA has been required with tests for LTBI.Persons with a chest radiograph or clinical signs or symptoms suggestive of TB must provide three sputum specimens for acid-fast bacillus microscopy and culture for mycobacteria.Use of both solid and liquid media is required for culture.Panel physicians may use molecular tests at their discretion for clinical purposes.The decision to clear an applicant with negative test results is based on the culture results.Drug susceptibility testing is required for positive cultures.Panel physicians use the liquid culture system for testing or may use molecular tests at their clinical discretion.Persons diagnosed with pulmonary TB disease are required to complete a course of directly observed therapy and have negative smear and culture results before applying for their visa to the United States. 7nalysis population.Our analytic dataset included followto-join asylees who were screened for TB overseas and arrived in the United States between 2014 and 2019.Data from overseas TB screening in follow-to-join asylees and postarrival evaluation in the United States for those at risk for TB were obtained from CDC's EDN database.Culture-based overseas TB screening classifies persons as 1) class B0 TB for those diagnosed with TB disease who complete a course of directly observed therapy overseas and are cured for TB disease, 2) class B1 pulmonary TB for those who have chest radiograph, HIV, or clinical signs/symptoms suggestive of TB but negative sputum cultures overseas and no diagnosis of pulmonary TB disease, 3) class B2 LTBI for those diagnosed with LTBI overseas, and 4) no TB classification. 9In this analysis, we excluded persons with class B1 extrapulmonary classifications.
Postarrival evaluation in the United States.The CDC routinely notifies state and local health departments of arriving at-risk immigrants, refugees, and follow-to-join asylees via its EDN database 7,11,12 and recommends that health department physicians conduct a postarrival evaluation.During the evaluation, health department physicians assign a TB diagnosis, treat TB disease, may offer preventive treatment to those with LTBI, and enter the evaluation data directly into CDC's EDN database. 11thics review.We did not assess risk factors for class B0 TB since convergence failed in the logistic regression (because of quasicomplete separation of data points).We calculated proportions completing the postarrival evaluation of newly arrived at-risk follow-to-join asylees and proportions of TB disease among those who completed postarrival evaluation.For those diagnosed with LTBI at postarrival evaluation, we also calculated proportions completing treatment of LTBI.
Treatment of LTBI at postarrival evaluation in the United States.Of 133 newly arrived follow-to-join asylees diagnosed with LTBI at postarrival evaluation, 122 (91.7%) were recommended for LTBI treatment, and of these, 83 (68.0%) initiated the treatment and 59 (48.4%) completed the treatment (Table 4).
Comparison with two previous studies of immigrants and refugees.Table 5 compares the results of our analysis with those of a study of culture-based overseas TB screening in U.S.-bound immigrants and refugees and the results of another study of postarrival evaluation of newly arrived immigrants and refugees. 7,11The rates of class B0 TB (i.e., recent completion of overseas TB treatment) and class B1 TB among U.S.-bound immigrants and refugees are 258 and 3,612 cases/100,000 persons, respectively, and the rate of class B2 LTBI is 13.5% among those for whom LTBI screening was required. 7In comparison, our analysis found that the rates of class B0 TB and class B1 TB among followto-join asylees were 152 and 1,781 cases/100,000 persons, respectively, and that the rate of class B2 LTBI is 6.0% among those for whom LTBI screening was required.
In comparing country-specific results of culture-based overseas TB screening for U.S.-bound follow-to-join asylees with previously reported statistics for U.S.-bound immigrants and refugees, 7 we focused on India and China, since only 0.8% of arrivals of follow-to-join asylees were from Mexico, the Philippines, and Vietnam.Rates of class B0 TB are 21 and 111 cases/100,000 persons among immigrants and refugees from India and China, respectively, 7 in comparison with 104 and 333 cases/100,000 persons in our study for follow-to-join asylees from India and China, respectively.The rates of class B1 TB are 1,410 and 2,304 cases/100,000 persons among immigrants and refugees from India and China, respectively, 7 in comparison with 2,386 and 1,805 cases/100,000 persons for follow-to-join asylees from India and China, respectively.
Our analysis found that 45.4% of follow-to-join asylees at risk for TB completed their postarrival evaluation within 1 year after their arrival in the United States.In comparison, 64.5% of newly arrived at-risk immigrants and refugees completed their postarrival evaluation. 11When compared with immigrants and refugees for whom LTBI treatment was recommended at postarrival evaluation, 11 follow-to-join asylees had a similar proportion initiating the treatment (68.0%versus 69.0%) but a higher proportion completing the treatment (48.4% versus 40.0%).

DISCUSSION
Our analysis showed that U.S.-bound follow-to-join asylees had a high risk for TB diagnosed overseas: 152 cases/100,000 persons for class B0 TB and 1,781 cases/100,000 persons for class B1 TB.We found that culture-based overseas TB screening in U.S.-bound follow-to-join asylees effectively diagnosed persons with TB disease and identified those at risk for TB.We also found that only 45.4% of newly arrived at-risk follow-to-join asylees completed their postarrival evaluation in the United States.
The epidemiology of TB in U.S.-bound follow-to-join asylees is largely unknown, since previous studies on culturebased overseas TB screening focus on U.S.-bound immigrants and refugees. 6,7Our analysis showed that U.S.-bound asylees had lower rates of class B0 TB, class B1 TB, and class B2 LTBI than U.S.-bound immigrants and refugees. 7These differences were likely, in part, due to various distributions of age and country of birth between U.S.-bound follow-to-join asylees and U.S.-bound immigrants and refugees.Of immigrants and refugees who are screened for TB overseas by culture-based algorithm in a previous study,     26.1% of persons are $ 45 years old and 47.1% are from countries with a WHO's estimated TB incidence of $ 100 cases/100,000 persons/year, respectively. 7In our analysis of follow-to-join asylees, 10.3% of persons were $ 45 years old and 42.9% were from countries with a WHO's estimated TB incidence of $ 100 cases/100,000 population/year.Additionally, we found that meeting criteria for class B1 TB or class B2 LTBI was associated with country of birth among follow-to-join asylees.The of class B1 TB was higher among follow-to-join asylees from Ethiopia, Nepal, and India than among those from China.Also in comparison with persons from China, the risk of class B2 LTBI was higher among those from Ethiopia and Eritrea but lower among those from Afghanistan.These results suggest that the yield of TB screening in U.S.-bound follow-to-join asylees depends on their country of origin, a finding that has been observed with other mobile populations. 14exico, the Philippines, Vietnam, India, and China are the top five countries of birth with the most reported TB cases in the United States. 13In comparison with immigrants and refugees reported in a previous study, 7 the rates of class B0 TB were higher among follow-to-join asylees from India and China, and the rates of class B1 TB were higher among follow-to-join asylees from India but lower among those from China.These results suggest that culture-based overseas TB screening in U.S.-bound follow-to-join asylees in India and China is important and effective, since 35.0% of follow-to-join asylees were from these two countries.
Completion of postarrival evaluation for newly arrived at-risk follow-to-join asylees was less frequent than that reported for immigrants and refugees. 11We expected that the proportion of newly arrived at-risk follow-to-join asylees completing the postarrival evaluation would be similar to the proportion for refugees since they both have 8 months of federally funded medical assistance after their arrival in the United States and receive support from domestic refugee health programs.Missed opportunities for preventing TB in follow-to-join asylees exist since the yield and impact of overseas TB screening also depend on the number of at-risk persons who complete postarrival evaluation in the United States.Health departments and the CDC need to develop strategies to increase the proportion completing the postarrival evaluation of newly arrived at-risk follow-to-join asylees.Previous studies indicate that the proportion completing the postarrival evaluation might be improved if quarantine stations and health departments have intensive outreach. 15,16ompletion of postarrival evaluation could also be increased if health departments have better contact information of newly arrived at-risk follow-to-join asylees. 5Education on TB for at-risk follow-to-join asylees by panel physicians during overseas TB screening or during the arrival process could likely increase their willingness to complete a postarrival evaluation in the United States. 16Other measures for improving the proportion completing the postarrival evaluation of follow-tojoin asylees include health department physicians having access to a fully electronic and complete record of their overseas medical examination and treatment of TB. 11 Latent TB infection diagnosis with discordant results in newly arrived non-U.S.-born persons is a challenge for U.S. TB control programs.A recent study has found that of 17,996 children with a positive overseas TST, 73.8% are negative when retested by IGRA in the United States; of 1,051 children with a positive overseas IGRA, 58.0% are negative when retested by IGRA in the United States. 17Treating LTBI in immigrants and refugees is cost-effective, 18,19 but it is also a challenge for ensuring completion of the treatment. 20A study in the United States and Canada has reported that only 49.3% of foreign-born persons who initiated LTBI treatment during 2007-2008 completed the treatment. 21Since it has been proven to be effective, 22,23 the CDC has recommended a shortened treatment regimen for LTBI. 24,25A systematic review and meta-analysis have found that shorter treatment regimens for LTBI in migrants are often associated with better outcomes. 26A study of treatment regimens for LTBI has reported that of patients on 9H (i.e., 9 months of daily isoniazid), 49.1% (27/55) completed treatment compared with 69.8% (187/269) of patients on 4R (4 months of daily rifampin) and 79.2% (99/125) of patients on 3HP (3 months of once-weekly isoniazid and rifapentine). 27But 51.6% of follow-to-join asylees for whom LTBI treatment was recommended at postarrival evaluation did not complete their treatment, suggesting that there is a need for developing new strategies.Compared with treatment outside of health departments, completion of LTBI treatment might be improved when health departments provide care and case management. 28Other strategies, such as offering LTBI treatment at overseas medical examinations, 29 should be studied and considered.
Data used in our analysis have several limitations.Misclassification of TB cases might have occurred at overseas screening and postarrival evaluation in the United States.Postarrival evaluation data were unavailable for 54.6% of newly arrived at-risk follow-to-join asylees.The number of U.S.-bound follow-to-join asylees with overseas TB classifications was small for some countries of birth.

CONCLUSION
In conclusion, culture-based overseas TB screening in U.S.-bound follow-to-join asylees is effective in identifying those with TB disease (class B0 TB) or those at risk for TB (class B1 TB and class B2 LTBI).Completion of postarrival evaluation in the United States for newly arrived follow-to-join asylees was less frequent than that reported for immigrants and refugees.
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TABLE 1
Results of culture-based overseas TB screening in U.S.-bound follow-to-join asylees who arrived in the United States, 2014-2019 LTBI 5 latent tuberculosis infection; NA 5 not applicable; TB 5 tuberculosis.*Tests of immune response to mycobacterial antigen are required for all persons aged 2-14 years in countries with a WHO-estimated TB incidence $20 cases/100,000 persons/year.Such tests are not routinely required for others.†Cases per 100,000 persons.‡ Top 10 countries of birth with the most follow-to-join asylees who arrived in the United States during 2014-2019.

TABLE 2
Evaluation of risk factors for class B1 TB and class B2 LTBI in U.S.-bound follow-to-join asylees, 2014-2019 LTBI 5 latent tuberculosis infection; NA 5 not applicable; OR 5 odds ratio; TB 5 tuberculosis.* Persons aged 2 to 14 years in countries with a WHO's estimated TB incidence of $ 20 cases/100,000 persons/year.† Top 10 countries of birth with the most follow-to-join asylees who arrived in the United States during 2014-2019.‡ Tests of immune response to mycobacterial antigen are not required for persons aged 2 to 14 years in Egypt.

TABLE 3
Results of postarrival evaluation in the United States of newly arrived at-risk follow-to-join asylees, 2014-2019 LTBI 5 latent tuberculosis infection; TB 5 tuberculosis.* None were diagnosed with culture-positive TB at postarrival evaluation in the United States.

TABLE 4
Results of LTBI treatment of newly arrived follow-to-join asylees who were diagnosed with LTBI at postarrival evaluation in the United States, 2014-2019

TABLE 5
Comparison of overseas TB screening and postarrival evaluation of follow-to-join asylees with previous studies of immigrants and refugees