USA’s expanded overseas tuberculosis screening program: a retrospective study in China
© Liang et al.; licensee BioMed Central. 2015
Received: 21 August 2014
Accepted: 17 February 2015
Published: 7 March 2015
To address increasing tuberculosis (TB) incidence in foreign-born populations, immigrant TB screening programs have been implemented in the USA. These programs are modified periodically, the effectiveness of which have been disputed. The aim of this retrospective study was to assess the value of the 2009 Technical Instructions for Tuberculosis Screening and Treatment Using Cultures and Directly Observed Therapy (CDOT TB TI) in a cohort of the USA permanent-resident applicants from China.
Standardized forms were used to collect demographic, clinical, and laboratory data of Chinese individuals screened at the Guangdong International Travel Healthcare Center for permanent residence in the USA between October 08, 2009 and December 31, 2012. Applicants’ data were further retrospectively evaluated by three experienced panel physicians and radiologists according to the 1991 Technical Instructions for Tuberculosis Screening and Treatment (TI). TB cases and characteristics identified by the 1991 and expanded 2009 programs were compared.
The CDOT TB TI identified more than twice as many TB cases that required treatment completion before clearance for travel than the 1991 TI (270 vs. 131). In addition, the expanded screening program identified more cases of negative sputum smear but positive culture (181 vs. 44), and more cases of radiography suggestive of inactive (22 vs. 3) and active (248 vs. 128) TB. Specifically, the 1991 TI screening program failed to identify 25/38 (65.79%) cases carrying drug-resistant isolates, and 13/131 (9.92%) would have been inappropriately treated. Moreover, 220/270 (81.48%) of the cases were asymptomatic, which were identified by screening and subsequently treated. Improved chest radiograph and sputum negative conversion occurred in all treated cases.
CDOT TB TI, a screening program that includes sputum culture and drug susceptibility tests, identifies a greater number of TB cases, likely contributing to the overall decrease in TB prevalence in host (USA) and origin (China) countries.
KeywordsBenefit Immigrant Overseas Screening Tuberculosis USA China
For industrialized countries with a low burden of tuberculosis (TB), the incidence of the disease is primarily attributed to foreign-born individuals originating from high-TB burden countries [1-8]. To combat this, programs for TB screening among immigrants have been instituted and evaluated [9,10]. Typically, screening involves chest radiograph (CXR) alone or with clinical examination, though sputum tests have recently been included [1,11]. However, these programs vary with regard to national legislation, resource availability, and public health risk management practices [1,11-13], and their coverage and effectiveness remain disputable [14,15].
As the country with the largest number of international migrants, the percentage of emigrant TB cases in the USA has increased substantially since the Centers for Disease Control and Prevention (CDC) began collecting data on place of birth in 1986 [16-19]. During this time, technical instruction and guidance for TB screening has periodically been modified [11,20,21]. Beginning in 1991, the CDC Technical Instructions for Tuberculosis Screening and Treatment (TI) required that individuals overseas applying for permanent residence in the USA undergo TB screening. For those suspected of having active pulmonary TB, laboratory investigation was required, but not sputum culture or drug susceptibility testing (DST) [18,21-23]. In 2007, these requirements were expanded to include sputum cultures for applicants with signs or symptoms of TB, an abnormal CXR suggestive of TB disease, or human immunodeficiency virus (HIV) infection. The updated version in 2009 was named as the TI Using Cultures and Directly Observed Therapy (CDOT TB TI). Additional revisions incorporated DST for positive cultures to guide treatment and a shorter validity period for travel clearance [22,23]. As a result, the expanded overseas screening protocol reduced the importation of active TB disease from Mexico, the Philippines, and Vietnam , resulting in an annual savings of $15 million . However, data from the countries of origin are needed to obtain definitive conclusions concerning the effect of CDOT TB TI on reduced importation of TB.
China has become the 4th largest source of migrants in the world . China is also ranked 4th of the top 5 source countries of TB-infected emigrants to the USA, and a large number of USA-bound immigrants with suspected TB are identified in overseas screening [19,20]. Although the expanded screening program was implemented in China in 2009, there are no current reports evaluating the effects of CDOT TB TI on TB epidemiology in USA-bound migrants or within China or other countries of origin. Therefore, we studied TB cases among applicants for permanent USA residence at the largest assigned panel site in China, the Guangdong International Travel Healthcare Center (GDITHC) of Guangdong Province. Specifically, we aimed to evaluate the effectiveness of the CDOT TB TI and identify factors that may aid other emigration and immigration countries with respect to TB incidence.
Study design and applicants
A retrospective study was conducted to assess the effectiveness of the expanded screening program (CDOT TB TI) on individuals applying for permanent USA residence at GDITHC between October 08, 2009 and December 31, 2012. In accordance with the CDOT TB TI, Chinese applicants ≥15 years of age require a medical history, physical examination and CXR; applicants 2–15 years of age require a medical history, physical examination and tuberculin skin test or interferon-gamma release assay and should undergo CXR evaluation if a tuberculin skin test ≥ 10 mm or interferon-gamma release assay is positive. Applicants with signs or symptoms of TB disease, an abnormal CXR suggestive of TB disease, or HIV infection are required to provide three consecutive morning sputum specimens. Sputum tests include a smear for acid-fast bacilli (AFB) and culture for Mycobacterium tuberculosis (MTB).
Applicants’ data were further retrospectively evaluated according to the 1991 TI for comparison. For these evaluations, three experienced panel physicians and radiologists were invited to review related CXRs and other clinical characteristics, and to provide a unanimous final decision.
Applicants with infectious pulmonary TB disease, including laryngeal and pleural TB, must undergo directly observed therapy at a CDC Division of Global Migration and Quarantine (DGMQ)-approved treatment site before travel is allowed. For those treated at non-DGMQ-approved sites, the evaluation must be repeated one year after completion of treatment prior to travel clearance. All treatment regimens are required to follow guidelines of the current American Thoracic Society/CDC/Infectious Diseases Society of America, which incorporate DST results.
Standardized forms were used to collect applicants’ demographic, clinical, and laboratory data from the working and surveillance database of GDITHC, including: date of birth, sex, medical history (including prior history of TB disease and treatment), physical examination findings, TB exposure, current TB symptoms and signs, HIV-test results, CXR findings, AFB sputum smear and MTB culture results, and treatment course and outcomes (up until March 31, 2014). To compare epidemiologic characteristics of TB among the applicants, Guangdong Province, and China as a whole, epidemiologic data were cited from two published articles describing the results of the Fifth National Survey on TB Disease conducted in 2010 [26,27].
All analyses were performed using SPSS 14.0 software (SPSS Inc., Chicago, IL, USA). A χ 2 or Fisher’s exact test was used to compare proportions. Two-tailed P < 0.05 was considered as statistically significant.
This study was exempt from approval by the GDITHC Review Board as it analyzed working and surveillance data that is routinely collected, and applicant-identifying information was removed.
Characteristics of TB cases identified under different technical instruction
CDOT TB TI (n)
1991 TI (n)
TB cases identified
Age group, y
Medical history investigation
TB now, on treatment
TB previous, treated
TB previous, untreated
TB previous suspect classification, untreated
Current TB symptoms
Chest radiograph characteristics
Consistent with inactive TB
Consistent with active TB
Positive AFB smear and MTB culture
Positive AFB smear and negative MTB culture
Negative AFB smear and positive MTB culture
Negative AFB smear and negative MTB culture
Drug susceptibility test for MTB isolates
Pan-susceptible to first-line anti-TB drugs
First-line primary-drug resistant
First-line acquired-drug resistant
Of the identified applicants, 227 completed their TB treatment, which lasted 6–12 mo (24 mo for the two MDR-TB cases). Culture negative conversion within 60 d was slightly higher for applicants treated at the DGMQ-approved sites compared with non-approved sites (97.5 vs. 94.5%). Two MDR-TB cases completed their directly observed therapy consisting of second-line drugs at GDITHC, while the other three cases were lost. After completion of treatment, CXR revealed improvements in lung lesions in 227 applicants, including the 22 cases with initial CXR findings suggestive of inactive TB. Only one case relapsed during the study period, involving an applicant who had completed a treatment course at a non-approved treatment site, and had been waiting for another year. Eight applicants were unable to emigrate to the USA after completing treatment as the validity period for travel clearance was too short (3 mo), despite the absence of positive culture conversion.
Previous studies have indicated that the inclusion of the MTB culture would identify an additional 250 TB cases per year in foreign-born individuals screened prior to USA entry [21,28]. In fact, the number of positive-culture TB cases detected among recent USA immigrant arrivals has dramatically decreased after implementing the expanded screening protocol . Consistent with this, the results of this study indicate the expanded overseas screening program prevented the emigration of more than double the TB cases from China, primarily from cases with negative AFB smears. Although such cases are less infectious, the prevalence of negative-smear TB cases among immigrants and refugees highlights the necessity for effective screening and management to protect public health .
The highest rates of TB cases occur near to the time of entering among foreign-born individuals in the USA , similar to other countries with a low TB epidemiology . Although the TB incidence typically drops among these immigrants after one or two years, foreign-born individuals are still more likely develop TB disease than native-born individuals, even after 20 years [28,31,32]. This is attributed to latent TB infection (LTBI), which presents an important and cost-effective opportunity for eliminating TB in host countries [5,6,8]. However, these studies may have included individuals who were considered free of active TB, or even had CXR suggestive of active TB, but may have had positive cultures if sputum tests were conducted. These cases then enter the host country with a TB suspect classification, which can be considered as LTBI, and would thus be diagnosed during subsequent domestic follow-ups. Between 63.6% and < 100% of these immigrants completed follow-up evaluations , as it is voluntary for individuals with suspect TB classification to visit a health department after entering the USA , and detection of missed cases is prolonged after arrival. This may contribute to the high TB incidence within the foreign-born population, even decades after entry.
The use of CXR-based TB screening protocols in foreign-born populations has been disputed in many countries [33-35]. In CDOT TB TI, CXR screening further evaluates cases with results indicating inactive pulmonary TB. The CDOT TB TI also stipulates that a greater number of these applicants undergo an MTB test (e.g. 3,212 vs. 248 with 1991 TI based on our findings). Moreover, inclusion of the sputum culture in the expanded TB screening program doubled the number of active TB cases that required completion of treatment before being allowed to emigrate from China to the USA.
More asymptomatic TB cases were detected at GDITHC than reported in the National Survey in 2010 [26,27]. An explanation for this is that immigration health screening represents an active case-finding method and identifies cases at an earlier stage of disease. Consequently, immediate treatment of these cases prevents the transmission of MTB within the surrounding population. The expanded CDOT TB TI provided early diagnosis and treatment for 258 applicants in this study. Importantly, 85.0% of the asymptomatic TB cases in this study were confirmed by bacterial culture, highlighting the value of the sputum test. In China and many developing countries, there is an insufficient number of capacity-qualified labs . Thus, panel sites that follow the CDOT TB TI and qualify for smear microscopy and culture and DST capacity can benefit the NTP of countries of origin by identifying and treating more cases .
Many of the TB applicants in this study ignored TB symptoms, similar to findings in the National Survey in China in 2000 and 2010 [26,37]. The mildness of the symptoms, along with insufficient knowledge and attitude concerning TB, likely contributed to the failure to seek treatment. Once arriving in the host country, unfamiliarity with the healthcare system and fear of being repatriated can further delay medical evaluation . Therefore, health screening of permanent residence applicants provides an opportunity for education and promotion of healthcare-related topics [9,13].
Several studies have questioned the quality of work performed at panel sites [11,18,21,39] despite the documented value of overseas screening [29,40]. The 0.3% TB detection rate at GDITHC was similar with other studies [11,13], though much lower than that in Vietnam (9.4%) . Indeed, the prevalence of TB has remarkably declined in China in recent years, only 459/100,000 in 2010 and 230/100,000 in Guangdong Province [26,27], largely because of a great effort from the NTP . A large proportion of applicants from our study were from Guangdong Province, thus, the 0.3% TB detection rate at GDITHC is reasonable and consistent with that of Guangdong Province and lower than national data. The age distribution and proportion of primary drug-resistant isolates of this study cohort were also similar to the survey in Guangdong.
The obvious disadvantage of the CDOT TB TI is that many applicants with CXR findings consistent with “old healed TB,” including those who do not need further treatment, are required to undergo a sputum test before being cleared for travel. This requirement imposes a lengthy delay, as results of sputum cultures can take 42 days, compared to obtaining results from the sputum smear test in one day. However, information related to prolonged wait times or the additional expense is not routinely collected during pre-visa medical evaluations. Extensive study should be carried out on this important topic of cost-effectiveness of the expanded overseas TB screening policy.
There are a few limitations of this study worth mentioning. First, the study cohort was entirely comprised of applicants at the GDITHC, one of the panel sites in China; thus, selection bias may play a role in this study. Second, due to lack of follow-up data of the studied group of applicants after arriving in the USA, the long-term implications of TB prevalence in the USA cannot be determined.
Compared to the 1991 TI, the CDOT TB TI identified a larger number of TB cases that require treatment prior to emigration, including asymptomatic cases and cases missed by the NTP. The inclusion of MTB cultures played a key role in finding cases that can be considered LTBI, which will likely impact results from domestic follow-ups. Overseas panel sites following CDOT TB TI can identify and treat more asymptomatic cases, serving as a useful supplement to the NTP. As global investment is the ideal long-term TB control strategy [24,41], programs such as the CDOT TB TI represent a viable, effective management system, as evidenced by the reduced prevalence of TB in China.
The authors thank Dr. Jianjun Yin of the Guangdong Institute of Tuberculosis Prevention and Control, and Dr. Haobin Kuang, Dr. Peng Xiao, and Dr. Shouyong Tan of the Guangzhou Chest Hospital for critical comments. We thank Dr. Lin Wu, Dr. Kui Zeng, and Dr. Liping Huang for technical support, and AmEditor Inc. for copyediting.
- Pareek M, Baussano I, Abubakar I, Dye C, Lalvani A. Evaluation of immigrant tuberculosis screening in industrialized countries. Emerg Infect Dis. 2012;18(9):1422–9.View ArticlePubMedPubMed CentralGoogle Scholar
- European Center for Disease Prevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance in Europe 2009. Stockholm: European Centre for Disease Prevention and Control; 2010.Google Scholar
- Centers for Disease Control and Prevention. Reported tuberculosis in the United States, 2009. Atlanta, USA; 2010 [http://www.cdc.gov/TB/statistics/reports/2009/pdf/report2009.pdf].
- Falzon D, Ait-Belghiti F. What is tuberculosis surveillance in the European Union telling us? Clin Infect Dis. 2007;44(10):1261–7.View ArticlePubMedGoogle Scholar
- Fok A, Numata Y, Schulzer M, FitzGerald MJ. Risk factors for clustering of tuberculosis cases: a systematic review of population-based molecular epidemiology studies. Int J Tuberc Lung Dis. 2008;12(5):480–92.PubMedGoogle Scholar
- Ricks PM, Cain KP, Oeltmann JE, Kammerer JS, Moonan PK. Estimating the burden of tuberculosis among foreign-born persons acquired prior to entering the U.S., 2005–2009. PLoS One. 2011;6(11):e27405.View ArticlePubMedPubMed CentralGoogle Scholar
- Kamper-Jorgensen Z, Andersen AB, Kok-Jensen A, Kamper-Jorgensen M, Bygbjerg IC, Andersen PH, et al. Migrant tuberculosis: the extent of transmission in a low burden country. BMC Infect Dis. 2012;12:60.View ArticlePubMedPubMed CentralGoogle Scholar
- Vanhomwegen J, Kwara A, Martin M, Gillani FS, Fontanet A, Mutungi P, et al. Impact of immigration on the molecular epidemiology of tuberculosis in Rhode island. J Clin Microbiol. 2011;49(3):834–44.View ArticlePubMedPubMed CentralGoogle Scholar
- Zimmerman C, Kiss L, Hossain M. Migration and health: a framework for 21st century policy-making. PLoS Med. 2011;8(5):e1001034.View ArticlePubMedPubMed CentralGoogle Scholar
- Coker R. Tuberculosis screening in migrants in selected European countries shows wide disparities. Eur Respir J. 2006;27(4):801–7.View ArticlePubMedGoogle Scholar
- Alvarez GG, Gushulak B, Abu Rumman K, Altpeter E, Chemtob D, Douglas P, et al. A comparative examination of tuberculosis immigration medical screening programs from selected countries with high immigration and low tuberculosis incidence rates. BMC Infect Dis. 2011;11:3.View ArticlePubMedPubMed CentralGoogle Scholar
- Mulder C, Klinkenberg E, Manissero D. Effectiveness of tuberculosis contact tracing among migrants and the foreign-born population. EuroSurveill. 2009,14(11). Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19153.
- Klinkenberg E, Manissero D, Semenza JC, Verver S. Migrant tuberculosis screening in the EU/EEA: yield, coverage and limitations. Eur Respir J. 2009;34(5):1180–9.View ArticlePubMedGoogle Scholar
- Coker R. Compulsory screening of immigrants for tuberculosis and HIV: is not based on adequate evidence, and has practical and ethical problems. BMJ. 2004;328(7435):298–300.View ArticlePubMedPubMed CentralGoogle Scholar
- Moore-Gillon J, Davies PD, Ormerod LP. Rethinking TB screening: politics, practicalities and the press. Thorax. 2010;65(8):663–5.View ArticlePubMedGoogle Scholar
- Centers for Disease Control and Prevention. Trends in tuberculosis incidence–United States, 2006. MMWR Morb Mortal Wkly Rep. 2007;56(11):245–50.Google Scholar
- Centers for Disease Control and Prevention. Trends in tuberculosis incidence—United States, 2008. MMWR Morb Mortal Wkly Rep. 2008;57(11):281–5.Google Scholar
- Binkin NJ, Zuber PL, Wells CD, Tipple MA, Castro KG. Overseas screening for tuberculosis in immigrants and refugees to the United States: current status. Clin Infect Dis. 1996;23(6):1226–32.View ArticlePubMedGoogle Scholar
- Liu Y, Painter JA, Posey DL, Cain KP, Weinberg MS, Maloney SA, et al. Estimating the impact of newly arrived foreign-born persons on tuberculosis in the United States. PLoS One. 2012;7(2):e32158.View ArticlePubMedPubMed CentralGoogle Scholar
- Lowenthal P, Westenhouse J, Moore M, Posey DL, Watt JP, Flood J. Reduced importation of tuberculosis after the implementation of an enhanced pre-immigration screening protocol. Int J Tuberc Lung Dis. 2011;15(6):761–6.View ArticlePubMedGoogle Scholar
- Maloney SA, Fielding KL, Laserson KF, Jones W, Nguyen TN, Dang QA, et al. Assessing the performance of overseas tuberculosis screening programs: a study among US-bound immigrants in Vietnam. Arch Intern Med. 2006;166(2):234–40.View ArticlePubMedGoogle Scholar
- Centers for Disease Control and Prevention. Immigration requirements: technical instructions for tuberculosis screening and treatment. Atlanta, GA, USA: Department of Health and Human Services, 2009. [http://www.cdc.gov/immigrantrefugeehealth/exams/ti/panel/tuberculosis-panel-technical-instructions.html]
- Centers for Disease Control and Prevention. Notice to readers: revised technical instructions for tuberculosis screening and treatment for panel physicians. MMWR Morb Mortal Wkly Rep. 2008;57(11):292–3.Google Scholar
- Posey DL, Naughton AP, Willacy EA, Russell M, Olson CK. Implementation of new TB screening requirements for U.S.-bound immigrants and refugees - 2007–2014. MMWR Morb Mortal Wkly Rep. 2014;63(11):234–6.PubMedGoogle Scholar
- Pew Research Center, Changing Patterns of Global Migration and Remittances. 2013 [http://www.pewsocialtrends.org/2013/12/17/changing-patterns-of-global-migration-and-remittances/]
- Zhong Q, Yin J, Qian M, Zhou L, Chen T, Li J, et al. Analysis of the 5th tuberculosis epidemiological sampling survey of Guangdong province. Chin J Antibiot. 2011;33(6):317–22 [http://www.zgflzz.cn/CN/Y2011/V33/I6/317].Google Scholar
- Technical Guaidance Group of the Fifth National TB Epidemological Survey; the Office of the Fifth National TB Epidemological Survey. The fifth national tuberculosis epidemiological survey in 2010. Chin J Antibiot. 2012;34(8):485–508 [http://www.zgflzz.cn/CN/Y2012/V34/I8/485]Google Scholar
- Cain KP, Benoit SR, Winston CA, Kenzie WRM. Tuberculosis among foreign-born persons in the United States. JAMA. 2008;300(4):405.View ArticlePubMedGoogle Scholar
- Liu Y, Weinberg MS, Ortega LS, Painter JA, Maloney SA. Overseas screening for tuberculosis in U.S.-bound immigrants and refugees. N Engl J Med. 2009;360(23):2406–15.View ArticlePubMedGoogle Scholar
- uberculosis Section, Health Protection Agency Centre for Infections. Tuberculosis in the UK: annual report on tuberculosis surveillance and control in the UK 2010. London: Health Protection Agency; 2010.Google Scholar
- Vos AM, Meima A, Verver S, Looman CW, Bos V, Borgdorff MW, et al. High incidence of pulmonary tuberculosis persists a decade after immigration, The Netherlands. Emerg Infect Dis. 2004;10(4):736–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Greenaway C, Sandoe A, Vissandjee B, Kitai I, Gruner D, Wobeser W, et al. Tuberculosis: evidence review for newly arriving immigrants and refugees. Can Med Assoc J. 2011;183(12):E939–51.View ArticleGoogle Scholar
- Dasgupta K, Menzies D. Cost-effectiveness of tuberculosis control strategies among immigrants and refugees. Eur Respir J. 2005;25(6):1107–16.View ArticlePubMedGoogle Scholar
- Koppaka R, Bock N. How reliable is chest radiography? In: Toman’s tuberculosis: case detection, treatment and monitoring. Questions and answers. 2nd ed. Geneva: WHO; 2004. p. 51–60.Google Scholar
- Mor Z, Leventhal A, Weiler-Ravell D, Peled N, Lerman Y. Chest radiography validity in screening pulmonary tuberculosis in immigrants from a high-burden country. Respir Care. 2012;57(7):1137–44.View ArticlePubMedGoogle Scholar
- World Health Organization. Global Tuberculosis Report 2013. Geneva, Switzerland; 2013 [http://apps.who.int/iris/bitstream/10665/91355/1/5239789241564656_eng.pdf?ua=1]
- National Technic Steering Group of the Epidemiological Sampling Survey for the Tuberculosis, Duanmu H. Report on fourth national epidemiological sampling survey of tuberculosis. Zhonghua Jie He He Hu Xi Za Zhi. 2002;25(1):3–7.Google Scholar
- Abarca TB, Pell C, Bueno CA, Guillen SJ, Pool R, Roura M. Tuberculosis in migrant populations: a systematic review of the qualitative literature. PLoS One. 2013;8(12):e82440.View ArticleGoogle Scholar
- King K, Douglas PJ, Beath K. Is premigration health screening for tuberculosis worthwhile? Med J Aust. 2011;195(9):534–7.View ArticlePubMedGoogle Scholar
- Mor Z, Leventhal A, Diacon AH, Finger R, Schoch OD. Tuberculosis screening in immigrants from high-prevalence countries: interview first or chest radiograph first? A pro/con debate. Respirology. 2013;18(3):432–8.View ArticlePubMedGoogle Scholar
- Schwartzman K, Oxlade O, Barr RG, Grimard F, Acosta I, Baez J, et al. Domestic returns from investment in the control of tuberculosis in other countries. N Engl J Med. 2005;353(10):1008–20.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.