Biological Health Hazard – Multidrug-resistant Tuberculosis (MDR-TB): European Union (migration related)
TUBERCULOSIS – EUROPE: MIGRATION IN THE EUROPEAN UNION, 2007-2013
Published Date: 2016-03-25 18:20:52
Subject: PRO/EDR> Tuberculosis – Europe: migration in the EU, 2007-2013
Archive Number: 20160325.4119523
Date: Thu 24 Mar 2016
Source: Eurosurveillance, Volume 21, Issue 12 [edited]
The effect of migration within the European Union/European Economic Area on the distribution of tuberculosis, 2007 to 2013
[authors: Hollo V, Kotila SM, Ködmön C, Zucs P, van der Werf MJ]
Immigration from tuberculosis (TB) high-incidence countries is known to contribute notably to the TB burden in low-incidence countries. However, the effect of migration enabled by the free movement of persons within the European Union (EU)/European Economic Area (EEA) on TB notification has not been analysed. We analysed TB surveillance data from 29 EU/EEA countries submitted for the years 2007-2013 to The European Surveillance System. We used place of birth and nationality as proxy indicators for native, other EU/EEA and non-EU/EEA origin of the TB cases and analysed the characteristics of the subgroups by origin. From 2007-2013, a total of 527 467 TB cases were reported, of which 129 781 (24.6%) were of foreign origin including 12 566 (2.4%) originating from EU/EEA countries other than the reporting country. The countries reporting most TB cases originating from other EU/EEA countries were Germany and Italy, and the largest proportion of TB cases in individuals came from Poland (n=1562) and Romania (n=6285). At EU/EEA level only a small proportion of foreign TB cases originated from other EU/EEA countries, however, the uneven distribution of this presumed importation may pose a challenge to TB programmes in some countries.
The epidemiology of communicable diseases can be affected by migration; between 2007 and 2011, around 40 per cent of HIV cases in the European Union (EU) and European Economic Area (EEA) were reported among migrants [1-3]. Migration from high-incidence countries (defined as incidence as 20 or more tuberculosis (TB) cases/100 000 inhabitants/year) is known to contribute notably to TB burden in low-incidence countries (under 20 TB cases/100 000 inhabitants/year) using the thresholds previously proposed by the Wolfheze working group  and adopted in the EU monitoring framework [5-14]. Persons with latent TB infection as well as patients with active TB and multidrug-resistant (MDR) TB can easily move from one country to another in the EU.
The free movement of persons within the EU is a fundamental right guaranteed to EU citizens by the Treaties . Before 2010, the migration flows within the EU/EEA were mainly from eastern European member states to member states in the south and west  . Driven by the economic crisis, from 2007 onwards, an increase was seen in numbers of people migrating from the countries most heavily affected by the depression (Greece, Spain, Italy, Ireland and Portugal) to western and northern EU countries . In 2013, 17.7 million EU citizens were living in an EU country other than their country of birth, corresponding to 3.5 per cent of the total population . The highest number of migrants from other EU countries resided in Germany (3 635 265; 4.4 per cent of the total population) and the lowest in Estonia (13 238; 1.0 per cent of the total population). Possible cross-border transmission of communicable diseases as a consequence of free movement of persons across the borders has raised concerns in some countries [19,20].
To our knowledge, the effect of migration within the EU/EEA on the epidemiology of TB has not been analysed previously. The objective of this study was therefore to estimate the extent of cross-border movement of TB cases within the EU/EEA. In addition, we aimed to characterise the ‘foreign’ TB cases originating from other EU/EEA countries, and to identify possible major patterns with respect to countries from which cases originate and which countries report such cases. Our quantitative descriptive analysis of the EU/EEA-wide TB surveillance data by geographical origin of cases may support decisions to implement targeted TB prevention and control measures where needed.
We carried out a descriptive analysis of all TB cases reported to The European Surveillance System (TESSy) by national surveillance institutes in 27 EU and two EEA countries from 2007 to 2013. Data collection methods and definitions are described elsewhere . Liechtenstein reported TB surveillance data to TESSy only in 2007 and Croatia joined the EU in July 2013, so both countries were excluded from the analysis.
After submission to TESSy, data are subjected to automated checks for completeness and accuracy followed by expert-driven manual data validation. For the calculation of notification rates, country population denominators were obtained from Eurostat http://www.epp.eurostat.ec.europa.eu. . Notification rates for ‘foreign TB cases’ of EU/EEA origin and non-EU/EEA origin, and for the native population were calculated only for 2013 due to incomplete historical population data stratified by area of origin from Eurostat .
Definition of native and foreign tuberculosis cases
For Austria, Belgium, Greece, Hungary and Poland, we used citizenship to assign geographic origin, for the remaining 24 countries place of birth was used as a proxy indicator for the geographic origin of a TB case. A ‘native TB case’ was defined as a TB case reported by the patient’s country of birth or citizenship, and a ‘foreign TB case’ as a case reported by a country different from the patient’s country of birth or citizenship. The foreign cases were further divided into cases originating from outside of the EU/EEA and cases from other EU/EEA countries. Cases defined as ‘foreign’ but with missing country of origin, were excluded from the analysis. Cases originating from countries that do not exist any longer — that is, ‘Soviet Union’, ‘Yugoslavia’, ‘Czechoslovakia’ were recoded as ‘foreign, country not specified’. TB cases originating from Greenland and Faroe Islands were considered as native Danish cases, and the cases originating from Jersey and Gibraltar were classified as native cases of the United Kingdom (UK).
We analysed the data by age and sex, site of disease, previous treatment, laboratory confirmation, and drug susceptibility testing results for the two main first-line anti-TB drugs (isoniazid and rifampicin), HIV co-infection and treatment success 12 months after start of treatment. The distribution of these variables was stratified by origin, excluding the unknowns where applicable. In a sensitivity analysis, we excluded all native cases reported by Romania and Poland. Both countries accounted for large shares of native cases and foreign cases reported by other EU/EEA countries while hardly reporting any cases of other EU/EEA origin themselves. The exclusion of Romanian and Polish native cases was thus meant to identify and avoid any potential bias resulting from largely comparing foreign and native cases from these 2 countries.
To compare incidence levels, countries were grouped as high- and low-incidence TB countries based on the data reported for 2013. Thus, high-incidence countries were 6 countries: Bulgaria, Estonia, Latvia, Lithuania, Portugal and Romania, and low-incidence countries all other EU/EEA countries.
For data analysis, we used Stata 13 (StataCorp LP, College Station, Texas, US) and Microsoft Excel 2010. Chi-squared tests were used to analyse differences between percentages. A p value of less than 0.01 was considered as statistically significant.
During the period 2007 to 2013, a total of 527 467 TB cases (notification rate 14.9/ 100 000) were reported of which 11 788 cases (2.2 per cent) were reported as ‘origin unknown’. Of these cases with unknown origin, 11 595 (98.4 per cent) were reported from countries defining origin by country of birth and 193 (1.6 per cent) from countries defining origin by citizenship. Of the remaining 515 679 cases, 385 898 (74.8 per cent) were reported as native and 129 781 (25.2 per cent) as foreign. Among foreign cases, 121 994 (94.0 per cent) were defined by country of birth and 7787 (6.0 per cent) by citizenship. Country of origin was reported for 104 491 (80.5 per cent) of all foreign cases whereas 25 290 (19.5 per cent) foreign cases were reported without country of birth/citizenship. Country-specific proportions of foreign TB cases with country of origin reported ranged from 0.1 per cent (213/147 843) in Romania to 85.7 per cent (2090/2438) in Norway. The vast majority, 91 925 (88.0 per cent) of foreign TB cases with known origin came from outside the EU/EEA. In total, 12 566 cases (2.4 per cent of all TB cases and 9.7 per cent of foreign TB cases) were reported to originate from another EU/EEA country. Country-specific proportions of foreign TB cases of EU/EEA origin varied between 0.05 per cent (9/18 365) in Bulgaria and 36.6 per cent (136/372) in Cyprus (table 1 [see source URL]). Most of the foreign TB cases of EU/EEA origin were diagnosed in Italy ( 3368; 12.2 per cent of all cases reported in Italy), Germany (2388; 7.7 per cent) and the UK (2089; 3.5 per cent). The proportion of TB cases originating from another EU/EEA country was reported to be below one per cent in 7 countries (Bulgaria, Latvia, Lithuania, Poland, Romania, Slovakia and Slovenia); 1–10 per cent in 18 countries (Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Malta, the Netherlands, Norway, Portugal, Spain, Sweden and UK) and more than 10 percent in Cyprus, Iceland, Italy and Luxembourg.
Even though the overall TB notification rate declined by 5 per cent annually from 2007 to 2013, the number of foreign TB cases from other EU/EEA countries increased from 1428 (1.7 per cent of all TB cases) in 2007 to 2093 (3.3 per cent) in 2013 (p under 0.01), while the overall number of foreign TB cases increased from 17 809 (21.2 per cent) in 2007 to 18 011 (28.0 per cent) in 2013 (figure 1 [see source URL]). In the same period, the number of cases with unknown origin decreased from 2384 (2.8 per cent) to 1407 (2.2 per cent).
Compared with native TB cases, cases from other EU/EEA countries were more frequently female, 15 to 44 years old and affected by pulmonary TB. Their previous treatment, culture result and treatment outcome were less commonly known, and they were less frequently successfully treated. In contrast, they were more frequently tested for susceptibility to TB drugs than native cases, but found to have 38 per cent less MDR TB. Finally, compared with native TB cases, cases from other EU/EEA countries were 60 per cent less frequently tested for HIV co-infection; those tested, however, were not significantly more often HIV-positive than native cases (table 2 [see source URL]).
A statistically significant difference (p under 0.01) between the native cases and TB cases originating from other EU/EEA countries was seen for all the clinical and microbiological characteristics except for the proportions of cases with unknown site of disease and the proportions of HIV-positive cases.
Excluding Romanian and Polish native cases from this analysis made no difference to these findings.
Notification rates by geographical origin of tuberculosis cases
Of the 64 327 TB cases notified in 2013, 44 909 (69.8 per cent) were native TB cases, providing a notification rate of 9.8 per 100 000 for the native population. Of the total number of foreign cases, 14 050 (21.8 per cent) were reported among foreigners originating from outside of the EU/EEA (notification rate 41.3/100 000 population), and 2093 (3.3 per cent) among foreigners originating from the EU/EEA outside of the reporting country (notification rate 11.9/100 000 population).
The vast majority, 2015 (96.3 per cent of all foreign cases from EU/EEA countries), of foreign TB cases originating from the EU/EEA, were reported in low-incidence countries and only 78 (3.7 per cent) were registered in high-incidence EU countries in 2013. As illustrated in Figure 2 [see source URL], in 2013 the notification rate per 100 000 migrant population with EU/EEA origin was 20.1 for high-incidence countries, which is about 1/3rd of the notification rate among the native population (55.2), and almost 2 times higher than the notification rate among foreigners coming from outside the EU/EEA (11.3). The notification rate of 11.7 per 100 000 population observed in low-incidence countries among foreigners originating from the EU/EEA is twice as high as among the national population (5.2), and less than 1/3rd of the notification rate of TB cases coming from outside of EU/EEA (42.6) (figure 2).
Country of origin of tuberculosis cases with foreign EU/EEA origin
TB cases originating from other EU/EEA countries, originated from 29 different countries: 6285 cases (50.0 per cent) from Romania, 1562 (12.4 per cent) from Poland, 704 (5.6 per cent) from Portugal, 563 (4.5 per cent) from Bulgaria, and 458 (3.6 per cent) from Italy (figure 3 [see source URL]).
At the EU/EEA level, the 7-year average proportion of cases originating from other EU/EEA countries was 2.4 per cent, but in some countries the share was much higher, reaching up to 36.6 per cent of all TB cases reported in Cyprus during 2007 to 2013, 33.6 per cent in Luxembourg, 11.0 per cent in Iceland and 12.2 per cent in Italy (table 1 [see source URL]). A vast majority (92.5 per cent) of TB cases from other EU/EEA countries reported by Italy originated from Romania, the country with the highest burden of TB in the EU/EEA.
Our results show that only 3.3 per cent (2093/64 327) of TB cases notified in the EU/EEA in 2013 originated from other EU/EEA countries. This roughly matches the 3.5 per cent of all persons residing in the EU that originated from other EU countries in 2013 . Therefore, free movement between countries within the EU/EEA does not seem overall to cause disproportionate challenges for TB prevention and control in the EU/EEA.
Throughout the study period, the proportion of foreign TB cases originating from other EU/EEA countries slowly increased from 1.7 to 3.3 per cent of all TB cases, while the percentage of native TB cases declined from 76.0 per cent to 69.8 per cent. There were notable differences between the numbers of TB cases originating from the respective countries and ‘foreign TB cases’ from EU/EEA reported by them. The migration flow of TB cases was mainly from TB high-incidence countries to low-incidence countries. This is expected since the TB burden is divided unevenly across the EU . In 2007 to 2013, Germany, Italy and the UK reported most foreign TB cases from other EU/EEA countries and Bulgaria, Poland and Romania were the countries from which most TB cases from EU/EEA countries reported by other EU/EEA countries originated. In 2013, the EU countries with the largest population of EU immigrants were France, Germany and the UK  and the EU countries with the highest numbers of emigrants were Poland, Romania and Spain . We do not see a clear pattern in the size of the migrant population from other EU/EEA countries and the number of foreign TB cases from other EU/EEA countries. This is expected as TB in migrants does not only depend on the size of the migrant population but also on the TB incidence in the country of origin and other factors such as living conditions of migrant populations and mixing patterns . In general, the level of TB transmission is not high between groups of different ethnic origin in the EU/EEA , however, it is not known whether this applies to the migrants originating from the other EU/EEA countries.
Our study design entails some limitations. In the absence of data indicating in which country the infection was contracted, we used the country of birth and citizenship as proxy indicators for origin of the TB cases. This might have led to under- or overestimation of the case numbers in the subgroups by geographical origin, for example if native cases actually got infected abroad, or if foreign cases were infected in their current country of residence. In addition, the comparability of data between countries is compromised by 3 factors: not all countries have reported all data for the whole period 2007 to 2013; the method of reporting differs between countries; and some reporting practices applied by individual countries, e.g. relating to origin, previous treatment, drug susceptibility testing and treatment outcome are not consistent over time. For the descriptive analysis presented here, possible interactions between parameters like sex ratio and age distribution of migrants have not been taken into account. Finally, underreporting of TB may have led to an underestimation of TB burden. Recent studies from England , Greece  and regions within Italy , the Netherlands , Romania  and Spain  have estimated underreporting to range between 15 per cent and 80 per cent. One of these studies, however, found that underreporting applied less to migrants than the native population (18 per cent vs 68 per cent) .
Our results show that drug susceptibility testing results were available more frequently for foreign TB cases of EU/EEA origin than native cases. This is supported by the fact that the main countries reporting TB cases in migrants of EU/EEA origin report higher proportions of drug susceptibility testing than the main countries reporting native cases, Romania and Poland. In 2007 to 2013, the proportion of MDR-TB was lower among foreign cases originating from other EU/EEA countries than in native cases. Also, of all MDR-TB cases reported by low-incidence countries of the EU/EEA, less than 10 per cent originated from other EU/EEA countries. This implies that migration within the EU/EEA is not the main driver of MDR-TB incidence in low-incidence EU/EEA countries.
The mean age of foreign TB cases of EU/EEA origin was lower than among the native TB cases. It is not surprising that most of the foreign TB cases of EU/EEA origin occur within the population at working age considering that the most frequent factor influencing the decision to migrate in the EU is employment , followed by family reunion, study and retirement. The proportion of culture-positive and of pulmonary cases was higher among migrants from EU/EEA countries than among natives. This could possibly be explained by migrants having a higher threshold for seeking healthcare in a foreign country and the challenge of accessing healthcare in a foreign country, leading to a delayed diagnosis and more advanced disease.
We noted that the completeness of data on TB treatment history was exceptionally low and the treatment outcome 12 months after start of treatment was less frequently reported for foreign cases originating from other EU/EEA countries compared with native cases and cases from non-EU/EEA countries. Persons diagnosed with TB in another EU/EEA country may decide to return to their country of origin for treatment. In this case the treatment outcome may not be made available to the country that diagnosed the case. The issues in cross-border exchange of TB case information have been identified before [31,32], and the need for facilitated referral and exchange of information between EU/EEA countries is evident.
In conclusion, the uneven distribution of TB diagnosed in persons originating from other EU/EEA countries within the EU/EEA may pose an incentive for coordinated EU action to improve TB programmes in individual countries. Awareness of the number of cases deriving from specific EU high-incidence countries can facilitate targeted TB prevention and control efforts in receiving countries, optimally in collaboration with the TB cases’ countries of origin. In all EU/EEA countries, however, the number of TB cases from non-EU/EEA countries was higher than the number of foreign TB cases originating from other EU/EEA countries , implying that TB control efforts addressing migrant populations should primarily focus on migrants coming from TB-endemic regions outside of the EU/EEA.
[Figures, tables and references are available at the source URL.]
[The success in TB control in the United States is tempered by the burden of TB among foreign-born persons residing in this country (http://www.cdcnpin.org/scripts/tb/tb.asp). The case rate among foreign-born persons is at least 8 times higher than among US-born persons. In 1991, 73 per cent of reported TB cases were among US-born persons (8.2 cases per 100 000) while 27 per cent were in foreign-born persons (33.9 per 100 000). By comparison, 55 per cent of TB cases in 2005 occurred in the foreign-born. From 2001 through 2005, the top 5 countries of origin of foreign-born persons with TB were Mexico, the Philippines, Viet Nam, India, and China.
The Centers for Disease Control and Prevention [CDC] estimates that in the US in 2003, 10.6 per cent of foreign-born persons with TB had TB with primary isoniazid resistance, compared with 4.6 per cent of US-born persons with TB (http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5412a1.htm). The proportion of primary multidrug resistant (MDR) TB cases (resistance to isoniazid plus rifampin) disproportionately affects foreign-born persons in the US. Since 1997, the percentage of US-born patients with primary MDR TB has remained below 1.0 per cent. However, of the total number of reported primary MDR TB cases, the proportion occurring in foreign-born persons increased from 25.3 per cent (103 of 407) in 1993 to 82.7 per cent (81 of 98) in 2011 (http://www.cdc.gov/tb/publications/factsheets/statistics/TBTrends.htm).
XDR TB is uncommon in the US, where 63 cases of XDR TB have been reported between 1993 and 2011 (http://www.cdc.gov/tb/publications/factsheets/drtb/xdrtb.htm). Four cases of XDR TB occurred in the US in 2011; all 4 were foreign-born persons (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6111a2.htm).
The CDC points out the challenge to TB control that shifting immigrant migration patterns within the US pose for some low-incidence states or local communities with minimal TB control programs, which may be ill-equipped to handle an abrupt increase of TB cases and unfamiliar cultural issues (http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5105a1.htm). – Mod.ML
A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/promed/p/11767.]
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