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Public Health (2006) 120, 712 723

www.elsevierhealth.com/journals/pubh

REVIEW ARTICLE

Balancing prevention and screening among international migrants with tuberculosis: Population mobility as the major epidemiological inuence in low-incidence nations
D.W. MacPhersona,b, B.D. Gushulaka,
a

Migration Health Consultants Inc., Hartackerstrasse 77/21190 Vienna, Austria Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada

Received 20 June 2005; received in revised form 4 February 2006; accepted 5 April 2006 Available online 7 July 2006

KEYWORDS
Policy; Tuberculosis; Immigration; Migration; Prevalence gaps; Screening

Summary Background: Tuberculosis infection and disease remain a signicant cause of global morbidity and mortality. The burden of tuberculosis disease is greatest in the developing nations of the world, although the effect of imported disease is observed in low-incidence tuberculosis regions, represented predominantly by high-income countries. In these regions, national tuberculosis control and elimination programmes are increasingly challenged to address disease in foreign-born residents. Immigration policies and shifting migration patterns over the past 5 decades have brought larger numbers of permanent and temporary residency migrants from high-prevalence regions of the world into low tuberculosis incidence environments. As a consequence, both national immigration policies and global health strategies for the control of tuberculosis share common interest in mobile populations moving from high-to-low prevalence regions. Existing immigration medical screening practices in major immigrant-receiving nations were often designed to prevent and manage the importation of contagious, active pulmonary tuberculosis disease. Such programmes may be limited in addressing the long-term consequences of latent tuberculosis infection in foreign-born residents. In nations with a low incidence of tuberculosis, a direct link can be found between the globalization of health factors related to international population movements, as observed with tuberculosis and immigration policies and practices. Continued migration from high-endemic tuberculosis regions will increasingly inuence the disease burden in low-endemic areas, and challenge local tuberculosis control and elimination programmes. Evidence-based approaches to meeting those challenges will allow for the effective use of resources and support ongoing programme evaluation. & 2006 The Royal Institute of Public Health. Published by Elsevier Ltd. All rights reserved.

Corresponding author.

E-mail address: brian.gushulak@aon.at (B.D. Gushulak). 0033-3506/$ - see front matter & 2006 The Royal Institute of Public Health. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.puhe.2006.05.002

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Tuberculosis prevention and screening In a comprehensive view of the diseases which we are called upon to study, three only are of wide and universal interesttuberculosis, cancer and syphilis. In almost every particular tuberculosis out tops the others. (William Olser) 713

Migration and tuberculosis management

Evolving population dynamics and the growing awareness of the long-term implications of low national birth rates and ageing have increased the importance of migration in many Western nations.5 For a number of nations such as Australia, Canada, Israel and the USA, immigration has been a sustained fundamental component of nation building (Fig. 1). In other nations, including many in Europe, migration has been more complex and has reected both inward and outward population ows. Historically, those movements resulted from shifting responses to exploration, colonization and conict. During the past 50 years, the processes of decolonialization and globalization have had greater inuence. Independent of historical migration patterns and immigration history, migration-receiving nations in most of the developed world have for some time reported low national TB incidence rates in native-born residents (Fig. 2). Some developed nations have specic areas of national TB concern, often centred on disadvantaged populations such as the homeless6 or aboriginal groups;7 however, these generally reect low numbers of total cases. The past 50 years has been associated with a signicant global realignment in the proles of international population ows. While regular processes involving immigrants and refugees have continued, recent migrant ows can now include other components. Examples are reected in large and irregular movements of refugee claimants or asylum seekers, others displaced by complex humanitarian crisis, people who have been trafcked and smuggled, temporary migrant workers and foreign students. The characteristics of modern mobile populations can inuence TB epidemiology at the migrants destinations.

Introduction
One of the major socio-medical advances of the past century has been the control of tuberculosis (TB) as a major public health issue in the developed world. A combination of advances in medical sciences, public health policy and socio-economic development contributed to the successful control of what had been a major cause of death, illness and disability. In many large urban areas in the time of Osler, TB was responsible for as much as 10% of reported mortality.1,2 Within the matter of a few decades, economically advanced nations saw TB become a relatively uncommon malady restricted to readily dened populations or demographically identiable risk groups. Although the incidence and prevalence of TB has dropped dramatically in nations with advancing socio-economic status, TB remains a major global challenge for developing nations, in which sociopolitical-economic growth and stability are limited.3 Continuing disparities between levels of development are often paralleled in the prevalence of TB infection. The persistence of these disparities sustains the risk of introducing active and potentially reactivating TB into nations in which domestic TB control has been achieved. Migration across high-prevalence to low-prevalence gradients will continue in response to shifting global population demographics and the migration of temporary and permanent residents.4 As migration becomes an increasingly important aspect of international population dynamics, TB associated with population mobility will remain a signicant social and public health issue in much of the low incidence world. It is in this context that migration (both regular and irregular) destined to the developed world, and global TB control frequently focused on the developing world, intersect. The success of TB control in the developing world depends on resource commitments related to local and regional economic development. At the same time, the continuing success of TB elimination programmes already achieved in developed regions of the world will be directly inuenced by the real and perceived threats of imported active and latent TB infection occurring in migrants from TB-endemic regions.

Annual Number of Immigrants Admitted as a Proportion of Total Population - Canada, USA, Australia; 1981-2000

1 0.8 0.6 % 0.4 0.2 0

19 89 19 91 19 95 19 85 19 97 19 81 19 83 19 87 19 93 19 99

Year Canada USA Australia

Figure 1 Annual number of immigrants admitted as a proportion of total population: Canada, USA and Australia: 19812000.113

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714 D.W. MacPherson, B.D. Gushulak

Figure 2 Tuberculosis (as of 21 March 2005): estimated TB incidence (all cases) per 100 000 per year. Source: WHO Stop TB Department3, website: www.who.int/gtb.

Regular and managed population mobility can be permanent, as in the case of immigrants and resettled refugees, or temporary, as observed in the movements of visitors, foreign students, skilled and manual labour and business travel. Irregular movements involve the arrivals of asylum seekers, refugee claimants, victims of human smuggling, and trafcking and illegal migration. Although both regular and irregular migratory ows affect local TB control efforts in low-incidence nations, regional and national population dynamics inuence the respective effects of those movements. In Western Europe, for example, the proportions and volumes of irregular migrants in relation to those admitted via regulated processes of immigration has increased signicantly, particularly during the past 2 decades.8

composed of European populations moving between European nations, colonies or former colonies. Beginning with the demise of the European international colonial structure, and continuing as a result of conict,9 geopolitical evolution10 and globalization,11 traditional global immigration patterns have evolved considerably. Currently, many permanent arrivals accepted by traditional immigrant-receiving nations originate from less developed regions of the world. Many of the migrant source countries have higher TB infection rates compared with destination nations. Examples can be observed in current migration ows to North America,12,13 Western Europe,14 Israel15 and Australia.16

Immigration authorities and the management of tuberculosis Changes in migration patterns

Since the 1960s, traditional immigration-receiving nations have observed shifts in source regions supplying immigrants. Historical immigration ows in the rst half of the 20th century were primarily For more than 100 years, a component of the immigration programmes of the major immigrationreceiving Western nations has included the medical examination of migrants.1719 Immigration screening originally took place after immigrant arrival at

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Tuberculosis prevention and screening quarantine and medical stations; a classic example is provided by the facility at Ellis Island in the USA.20 After the First World War, major immigration-receiving nations established offshore medical screening conducted before immigrant departure.21 That model when applied to TB is intended to reduce the importation of disease, and has been used by nations with extensive international immigration recruiting programmes such as Australia, Canada and the USA. Other nations, including several in Europe, have continued to use on-arrival screening and assessment to identify and manage imported infections such as TB. In nations using routine immigration medical screening, the mandates related to immigration health are most often designed to prevent or mitigate the admission of migrants who pose public health threats. As a consequence, immigrationrelated TB screening was designed to manage active pulmonary disease that could be transmitted person-to-person creating events of public health signicance. As active infectious pulmonary disease presents the greatest public health risk, immigration medical screening for TB has been primarily based on chest radiography, reecting the historical, logistical and operational legacies of those principles.2224. In spite of its wide use, routine radiological screening has diagnostic and prognostic limitations.25 Routine immigration TB screening by radiology is commonly applied to immigrant applicants beginning in mid-adolescence. This practice reects historical clinical experience, suggesting that most paediatric pulmonary cases are pauci-bacillary, and the risk of secondary TB transmission from an infected child is low. As a consequence, most immigration-related TB screening, which is intended to reduce the importation and transmission of infection, is not focused on the management of paediatric TB infection or disease.26 The diagnosis of TB in children27 and the shifting epidemiology of TB disease,28 including HIV co-infected individuals, have implications for paediatric TB,29 which may require reconsideration of current approaches. In the immigration context, radiographic screening suggesting active pulmonary disease precipitates a medical referral for TB management. That may include additional clinical assessment, secretion bacteriological examination, culture and, if indicated, TB treatment and clinical follow-up for determination of cure. For most nations with predeparture screening programmes, migrants with active, infectious TB disease are denied admission and referred for treatment before arrival; those with inactive, latent TB infection (LTBI), or noninfectious presentations, are referred for public 715 health follow-up and clinical management after arrival. Nations using on-arrival screening commonly refer active and latent disease to local authorities for management and follow-up.

Migration effects on domestic tuberculosis epidemiology

At present TB remains a major cause of global morbidity and mortality. In 1993, the World Health Organization (WHO) recognized TB as a global public health emergency. In its 2005 annual report on global TB, the WHO noted that, since 1980, it has received reports on 81 million people with TB detected through its surveillance unit; this included 17 million people notied by the DOTS programme (DOTS directly observed treatment scheme) since 1995.30 The WHO estimates that globally about 8 million new cases of TB occur each year, and that 1 million deaths annually may be attributable to TB disease. The shift in migration patterns from regions of the world with elevated TB prevalence has combined to markedly affect the epidemiology of the disease in immigration-receiving nations (Table 1). During the past 3 decades, the proportion of cases of TB reported in the foreign-born residents has steadily increased in many low-incidence nations.3133. Population mobility and migration from regions of higher incidence are the major driving force behind this phenomenon. In countries with declining endemic caseloads, such as Australia,34 Canada,35 Norway,36 the Netherlands37 and the USA,38 the main proportion of national TB cases

Table 1 Number of cases of tuberculosis notied to the World Health Organization103 and estimated percent of total cases by foreign birth Country Reported cases of tuberculosis in 2003 1013 1451 5740 6526 505 1282 320 554 6400 14 861 Total case in foreign born (%) 80 66 41 38 85 61 76 51 64 51

Australia Canada France Germany Israel Netherlands Norway Switzerland UK USA

Adapted from World Health Organization.30

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716 are foreign-born residents. In the UK in 2003, those born abroad represented 70% of the national caseload.39 D.W. MacPherson, B.D. Gushulak that do not practice pre-arrival screening. Transmission of TB from foreign-born individuals infected after arrival does occur, but this transmission most commonly takes place within dened socio-economic or cultural groupings,45 including high-risk clusters such as homeless people, chronic alcoholics46 and the migrant community47 itself. The rare exceptions to within community transmission often attract media attention and increase general public concerns related to TB and foreign-born residents.48

Latent tuberculosis infection and disease in the foreign born residents living in lowincidence countries
As described above, most immigration-related TB screening was designed and directed towards the detection of active, transmissible pulmonary disease in adolescents and adults that was present at the time of the immigration medical examination. The routine detection and management of LTBI has not been a primary component of immigration medical screening in the countries carrying out this examination. Radiological screening, while useful in identifying abnormalities suggestive of pulmonary disease in high prevalence situations,40 is not a tool for the detection of latent TB infection. Compared with host populations in low-incidence nations, rates of LTBI are elevated in many migrant groups.4143 Consequently, over time, large-scale migration from high-prevalence locations has introduced large numbers of latently infected people to lower incidence, immigration-receiving nations. Without preventive treatment, some of those individuals will experience disease reactivation related to the natural history of TB infection. Investigation of TB in the foreign-born residents in immigration-receiving nations shows that most cases of TB in migrant cohorts are due to reactivation of TB infection acquired before arrival.44 These ndings are similar in those nations with established pre-departure immigration medical screening programmes, as well as those nations

Migration effects on traditional tuberculosis control programmes in low-incidence areas

The effect and programme outcomes resulting from shifting TB epidemiology due to immigration have been predictable and logical. Effective TB control programmes continue to maintain low domestic incidence rates in high-income nations. The USA experienced a temporary exception to this decline in TB cases during the 1990s, which was overcome with major re-investment in public health and TB control efforts.49 However, the change in migrant demography towards a growing number of arrivals from regions of the world where infection with TB is common (Table 2) now requires the direction of more efforts towards disease mitigation and prevention in migrant and mobile populations. This shifting epidemiological dynamic can create new and signicant challenges to domestic TB control and elimination programmes.50

Table 2

Tuberculosis incidence, prevalence, notication and case notication: rates by region 2003 Incidence 2003 (including HIV +) 8 810 000 Incidence rate 140/100 000 3 061 567 2 371 745 1 933 054 634 112 438 960 370 170 Prevalence 2003 (including HIV +) 15 430 000 Prevalence rate 245/100 000 5 661 702 3 486 914 4 081 006 1 119 950 577 371 502 605 Number of cases of tuberculosis notied in 2003 Case notication rate/100 000 in 2003

World region/ location Global

South East Asia Africa Western Pacic Eastern Mediterranean Europe The Americas

1 552 625 1 072 671 987 927 209 941 338 643 227 551

96 156 57 41 39 26

Adapted from World Health Organization.30

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Tuberculosis prevention and screening 717 health issues. As metropolitan locations are also regions in which other risk groups for TB are more common (e.g. homeless people, substance abusers and those living with HIV/AIDS), the additional burden imposed by migrants, if not anticipated and planned for, may exacerbate the existing demands on control resources.

Policy challenges
Many national TB control programmes in the developed world include, or are based on, policy principles of disease elimination. Although this goal is potentially possible in a closed environment, national disease elimination programmes are unlikely to be successful when most of the caseload originates in TB high-endemic immigration source countries. Nations with large immigration programmes and co-existing TB elimination programmes are functionally at the dialectic centre of two opposing forces. In these situations, national policies directed at TB elimination will only be successful when the disease is controlled globally or at least in the source countries supplying migrants. Policy makers will be increasingly required to balance the benets of greater investment in domestic elimination with support for international strategies to reduce the total global burden of the disease.51,52 Migrants can also be faced with several local and national policy barriers that can limit access to public health control and healthcare services treatment programmes, including TB services. These can be institutional, such as in situations in which services are unavailable for the uninsured, or those who are not eligible for social programmes (i.e. undocumented or illegal migrants). Fear of interacting with local health institutions and subsequent referral to immigration or security services may also limit access to care for the irregular migrants or illegal aliens.53 Barriers to access, such as language, culture or social factors, may also be encountered.54 National policies and strategies developed to deal with these barriers and limits include the provision of services for migrants without charge, medical insurance programmes or national support for migrant health, and the development of specialized centres with cultural competency and linguistic capacity for diverse populations.55

Mycobacterium drug resistance

Many of the factors present in regions of the world in which TB incidence is elevated, such as limited human and economic resources, non-existent or over-stressed public health systems, and insufcient or unreliable drug supplies, may also increase the risk of drug-resistant TB infection. Several areas, dened by the WHO as hotspots for drugresistant disease, are also the sources of a signicant number of migrants to low-endemic, Western nations.58,59 Low incidence, immigrationreceiving nations report that the cases in foreignborn residents show elevated incidence of Mycobacterium tuberculosis drug resistance (MDR-TB) in national surveys.60 However, as with total TB caseloads, although the proportion of MDR-TB disease is higher for migrants, the total number of cases remains relatively low.

Co-infection
The occurrence of co-morbid medical conditions associated with TB reactivation61 may also be differentially distributed in some migrant populations compared with TB in native-born populations. This includes HIV/AIDS in asylum seekers, refugees and immigrants,62 and malnutrition in some migrant and refugee63 populations. Co-infection with TB and HIV/AIDS can be complicated to manage64,65 owing to diagnostic difculties and clinical challenges, including drug interactions, adverse drug events, effects of immune reconstitution, the natural history of each infection being co-dependent on the course of the other, and the potential for emergence of drug resistance in either infecting organism. These complexities in clinical management are also reected in determining primary causes of morbidity and mortality in dually infected individuals.66 There is emerging evidence that patients with HIV/AIDS infected with TB and receiving highly active anti-retroviral treatment have a signicantly increased risk of TB disease compared with patients with HIV/AIDS with a history of TB infection.67 Studies of HIVTB coinfection in migrant populations in Western countries are limited; however, the challenges and

Operational challenges
Immigrants and refugees are, at least initially in the post-arrival period, more likely to reside in major urban rather than rural settings.56 The association of a growing proportion of TB case distribution in foreign-born residents has been accompanied with an increasing proportion of TB in metropolitan areas in immigration-receiving nations.57 The proportional urbanization of case burden can generate additional resource pressures on metropolitan areas faced with other public

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718 difculties in dealing with migrants with HIV/AIDS alone are complex68 in themselves. Lessons learned in nations with large immigration programmes, will be important for nations in which immigration is a newer phenomenon. D.W. MacPherson, B.D. Gushulak remain in the UK for more than 6 months, began in late 2005. By February of 2006, screening was under way in Bangladesh, Tanzania, Sudan, Cambodia and Thailand.79 Planned extension of the screening programme depends on the evaluation of the process. The effect of admission of migrants with LTBI is an issue of current investigation in many low-incidence nations with active immigration processing programmes.80 Because of its lack of sensitivity, radiological screening alone will not detect latent disease in infected people. In the absence of targeted screening for LTBI, future reactivation of latent disease in foreign-born residents can be predicted to continue to generate domesticTB cases, in spite of immigration-screening programmes.81 In some nations with immigration medical screening programmes, it has been suggested that routine immigration screening could be expanded to include testing for latent disease.82 Opinion expressed in other immigration-receiving nations, such as Canada,83 have concluded that such processes may not be indicated. The logistical and operational complexities of undertaking TB infection screening by tuberculin skin testing (TST) using puried protein derivative in multiple and diverse locations, particularly in an international setting, are daunting. The quality-management programmes necessary to put TST screening in place would be costly for both the programme and migrant. Newer diagnostic and clinical screening technologies are evolving for the direct detection of M. tuberculosis in mycobacteriological cultures or clinical specimens.84 In addition, antigen and serological tests are being evaluated in certain TB at-risk populations for their ability to detect infection.8591 These technologically advanced tests, including high expectations from the use of the Gamma-interferon assay,92,93 may provide operational and logistical advantages for singlestage testing for existing infection and latent disease, with improvement in the predictive value for progression to active disease. For certain highrisk populations who are already within Western healthcare service delivery environments, this approach may have benets exceeding the use of the TST. For nations that routinely screen migrants for TB, the application of either TST or newer technologies in an overseas environment would certainly present logistical and operational barriers, including cost, compliance, quality management and interpretative response over a diverse screening network. Testing foreign-born populations for latent infection is only one part of the potential solution to the contribution of imported TB on domestic disease

The future of immigration medical screening

Immigration medical screening is a legally mandated requirement for all applicants for permanent residency and certain categories of temporary resident applicants in traditional immigration processing and receiving nations. Other nations selectively screen some migrants or refer those who are noted to be clinically ill for more involved medical attention during immigration processing and formalities. The goal of detecting active, infectious pulmonary TB is a component of all of these programmes. The regular screening of higher risk migrants entering European nations was recommended in the mid-1990s.69 Recent surveys indicate that as many as half of the continental nations do not have organized screening programmes, and that there is considerable divergence in the application of existing programmes70 in those that do. Increasing attention to the issue of TB and migration has stimulated renewed interest in screening. Some studies suggest that existing migrant medical screening for TB may have some degree of effectiveness in reducing the immediate risk of the importation of contagious TB.71,72 Most tuberculosis presenting in migrants occurs after the immediate arrival period, and is believed to represent reactivation of latent infection. When reactivation does occur after migration, TB transmission from migrants to host populations occurs with low frequency,73 and, with some exceptions,74 national TB case rates continue to decrease or remain at recent historical levels, in spite of the changes in population demographics due to immigration. In spite of low domestic caseloads, the growing proportion of the national TB caseload occurring in the foreign-born residents has resulted in greater attention to migration-associated TB. Historically, the UK has relied on post-arrival identication and referral of new arrivals for medical evaluation, including TB screening.75 After extensive review76 and considerable scientic discussion,77 the UK has recently adopted systematic pre-departure screening for TB in certain locations.78 In a manner similar to policies used by Australia, Canada and the USA, screening based on routine radiological examination of people over 11 years of age, who would

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Tuberculosis prevention and screening burden. Only a small number of individuals with LTBI will progress to active disease.94 It is often estimated that the lifetime risk of active TB is about 10% in the immune-competent, TB-infected host,95 with about half of that risk of clinical disease in migrants occurring during the rst 35 years after arrival.96 Given the prevalence of LTBI in migrant populations from high endemic TB regions, providing management services that include appropriate preventative treatment for latent disease would be a major undertaking for a clinical programme. Design and implementation of such programmes would need to be accompanied by consideration of the effect of several other factors, including surveillance, notication, contact tracing, reporting, monitoring, evaluation, delivery, side-effects, compliance and costbenet, in addition to social enforcement issues.97,98. In some low incidence nations, migrant-targeted strategies also include detailed and complex follow-up of disease-free, but high-incidence populations.99 Reporting and analysis of longitudinal surveys of this type may allow for better understanding of the clinical predictive risk factors for reactivation, thus allowing for the improved targeting of preventive therapy and follow-up for those cohorts at greater disease risk and of higher public health interest.100 719 nding to support national TB control and elimination programmes. The result may be low-incidence nations expending considerable human and scal resources to manage TB caseloads post facto in environments in which domestic sources of cases are, on global scales, relatively rare, and where most foreign-born cases have their origin beyond national boundaries. To resolve this paradox, it will be necessary to focus increased resource investments from the local and national levels in low-incidence nations towards TB control and prevention programmes in high-incidence immigration source regions of the world.105 Such investments and effort in reducing the disease burden in those locations will bear twofold benet. Global TB control will be more effectively supported, and there will be a secondary effect of reducing migration-associated disease in immigration-receiving nations.

Conclusion
Migration from high incidence TB areas of the world will continue to be one of the most important factors in determining TB epidemiology in the developed world. Lessons learnt from national TB control programmes in immigration-receiving nations might benet and support policy and programme co-ordination and international harmonization within the global TB control strategies.106 Nations without current formal immigration screening programmes, but growing immigration levels, could learn valuable lessons from those countries that have longstanding immigration medical screening programmes.107110. TB provides a window through which the globalization of other health issues can be modelled. The effectiveness of well-dened, existing legislative and regulatory processes can be studied in the light of international health and infectious disease challenges in both clinical and public health sectors. These lessons may have relevance for those managing emerging health issues111 in an increasingly globalized world. The principles of TB control, elimination and eradication provide specic context regarding the interface between national and international interests in development, global public health,112 policy harmonization and integrated programme delivery.

Challenges related to migration in lowincidence nations

Current global policy realities indicate that the parallel global processes of increased population mobility in a world where TB infection remains high in migrant source regions will continue. Those population dynamics will continue to affect domestic epidemiology in low-incidence nations.101 In those nations, most new cases of TB will continue to be generated by migration from beyond their borders.102 This consideration is important, as its appreciation is necessary for the development of appropriate policy and programmatic responses to deal with the international component of domestic disease epidemiology. TB control strategies based on reducing disease transmission through the early diagnosis of the active disease through case nding during immigration screening may reduce the amount of active disease presenting in newly arrived migrants. However, this approach will have limited effect on the imported disease risk related to migration of those with LTBI103,104 or inactive, untreated disease. Low-incidence nations with large immigration programmes will increasingly require targeted case

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