Tuberculosis (TB) continues to be a global public health problem worldwide. According to the World Health Organization (WHO) report of 2017, 10.4 million cases were diagnosed worldwide in 2016. A total of 65% of cases occurred in men, 10% in persons living with HIV (PLHIV), and 56% were concentrated in 5 countries: India, Indonesia, China, the Philippines and Pakistan. In all, 3% of cases (290,000 cases) occurred in Europe, with an incidence of 32 cases/100,000 inhabitants.1 In the same period, the incidence of notified cases was 10.7 and 13.3 cases/100,000 inhabitants in Spain as a whole and in Catalonia, respectively and was 16.6 cases/100,000 inhabitants in the city of Barcelona.2,3

Since active drugs against Mycobacterium tuberculosis became available, the most effective measures for TB control and treatment success are early diagnoses and adherence to anti-TB therapy. Given that treatments are long, even those shortened to 6 months, treatment adherence is essential to achieve TB control targets. Indeed, as observed with other chronic transmissible infections such as PLHIV, non-adherence to treatment has a human, economic and very important social cost. Treatment discontinuation reduces its effectiveness, increases transmission, and causes drug resistance, thus increasing morbidity, mortality and more widespread infection. These diseases mainly affect economically and socially disadvantaged groups and may require complex treatment regimens. They are thus a public health priority.4

According to the WHO report on long-term treatment adherence, adherence can be defined as the extent to which a person's behavior corresponds to the recommendations agreed with the health provider. The patient's context is determined by factors related to his or her socioeconomic status, the healthcare team or health system, the disease, treatment, and individual characteristics. Consequently, these factors need to be targeted in interventions to prevent treatment discontinuation.5

The Barcelona TB prevention and control program (TBPCP) was created in 1987, and public health nurses (PHN) played an essential role in following-up TB cases and conducting contact tracing. In its early beginnings, the program encouraged directly observed treatment (DOT) for homeless persons with TB in the inner city (Ciutat Vella) and progressively guaranteed community- or hospital-based DOT for patients showing poor adherence.6 Community health workers (CHW) were incorporated in 2003 because of the increase in immigration from countries with a high TB burden, and their role was to support public health nurses and act as cultural mediators and translators.7 Later, five TB clinical units (TBCU) were created, located at the four large hospitals in Barcelona and in a specialist TB outpatient unit. A key figure in these units is the nurse case manager, who follows up TB patients, performs contact tracing, and supervises treatments always in coordination with public health nurses from TBPCP as well as with other professionals.8 Therefore, this has made it possible to increase TB treatment adherence until 88.5%.3

The aim of this study was to identify the sociodemographic and epidemiological characteristics of TB cases, the incidents occurring during treatment that could influence treatment adherence and contact tracing, the interventions performed to promote adherence comparing foreign-born and Spanish-born patients in a hospital from the inner city of Barcelona with a TBCU, the Mar Hospital, with a population reference of 336,900 inhabitants living in the districts of Sant Martí and Ciutat Vella in Barcelona.

During the study period, 172 TB cases were treated in the TBCU of Mar Hospital. A total of 40% and 55% occurred among residents of Ciutat Vella and Sant Martí districts, respectively. The distribution of cases and incidence of TB according to district are presented in Table 1. The table shows a higher incidence of tuberculosis in Ciutat Vella in relation to Sant Marti and Barcelona.

Of the 172 patients included, 106 (61.6%) were men. The median age was 43 years (IQR: 32.2–56). A total of 107 (62.2%) were foreign-born, of which 54 (31.3%) were born in the Indian subcontinent, 12 (6.9%) in Latin America, and 12 (6.9%) in Eastern Europe, while 9 patients were born in Morocco and 9 in the Philippines. Table 2 compares socio-demographic characteristics and clinical variables among Spanish and foreign-born patients.

In all, 134 patients (78.0%) lived in low- or low-medium income neighborhoods and 81 (47.1%) were employed. At least one risk factor for TB was present in 103 patients (59.9%). Disease localization was pulmonary or mixed in 100 patients (58.1%) and resistance to anti-TB drugs was detected in 12 patients (7%), one of whom showed multiresistance. Treatment success was achieved in 150 patients (86.6%), 5 (2.9%) moved to other autonomous communities of Spain or abroad, 4 (2.3%) were lost to follow-up, and 13 (7.5%) died (2 due to TB) (see Table 2).

Comparison of data from foreign and native-born patients revealed statistically significant differences: foreign-born patients contracted TB at younger ages, lived in neighborhoods with lower incomes, and a higher percentage were unemployed. A larger proportion of native-born patients were pensioners. Pulmonary localization was more common among native-born patients. There were no differences in treatment conclusion between the two groups. A comparison of sociodemographic, clinical and epidemiological factors between foreign and native-born patients is shown in Table 2.

Incidents occurred during follow-up in 151 patients (87.8%) with a median of 2 incidents per patient (IQR: 0–7). Medication-related complications occurred in 74 patients (43%), and exacerbation of comorbidities in 41 (23.8%).59 patients (34.3%) failed to attend follow-up visits in at least one occasion, and 33 patients (19.2%) reported traveling abroad during treatment (see Table 3).

Communication problems were detected in 44 patients (25.6%) and 25 patients (14.5%) changed address; of these, 19 (76%) had pulmonary TB. Another effect of TB diagnosis was stigmatization: 3 patients (1.7%) lost their jobs, 29 (16.9%) showed attitudes influenced by fear of social rejection (not mentioning their diagnosis to cohabitants or at work, not accepting DOT due to fear of rejection by neighbors and/or discrimination in their environment). Compared with Spanish-born, foreign-born patients showed a higher number of threats during treatment, traveled more often, missed more follow-up visits, and had more problems of unstable housing (p<0.05). A comparison of incidents during treatment between native and foreign-born patients is shown in Table 3.

Various strategies were used to maintain adherence. DOT was conducted in a specialized intermediate care center in 82 patients (47.7%), either as long term inpatients or community based DOT outpatients. Extra reports were issued for 85 patients (49.4%), and additional visits were scheduled for 41 (23.8%). Cultural mediation during hospital visits was provided for 27 patients (15.7%), while CHW from the ASPB intervened in 40 patients (13.3%). The PHN and the hospital-based nurse case manager made follow-up telephone calls and coordinated with different healthcare levels in 112 patients (65.1%). Contact tracing was conducted in 79 patients with pulmonary TB (79%) and in 36 with non-pulmonary TB (50%). Eight patients lived alone (4.7%) and 13 refused contact tracing (7.6%) (see Table 4).

Foreign-born required more reports, additional visits and telephone calls and were also more frequently referred to DOT centers. There was no statistical differences between Spanish-born and foreign-born patients regarding to contact tracing coverage. The strategies used to maintain adherence by country of origin (native or foreign-born) are shown in Table 4.

The profile of persons diagnosed in this study corresponded to young adults (median age, 43 years), from countries with a high TB burden, especially the Indian subcontinent, of working age and living in low-income neighborhoods. As in other countries in the European Union, these patients had other risk factors in addition to being immigrants, such as immunosuppression, alcohol abuse, tobacco use, psychoactive substance use and, sometimes, problems with the law.15 Other risk factors were social vulnerability, low socioeconomic position, precarious employment not covering basic needs, unhealthy lifestyles and low individual perception of risk, with little appreciation of the personal and community effects of the disease.16 This at-risk population is most numerous in Ciutat Vella,17 an inner city district of Barcelona that, as in London18 or Rotterdam,19 is characterized by being situated in the city center, with a large socially deprived population and an incidence of TB three times higher than that of the city as a whole. Moreover, in Ciutat Vella, there is a higher percentage of those foreign-born compared to the city of Barcelona, as well as a higher incidence of TB due to the high burden of disease in the foreign-born population.2,3,7,17

In this study, we found that a lot and different social, economic and treatment-related threats usually happen during the long treatment period required in TB patients. In agreement with the findings of studies conducted in other countries with a high TB burden such as Colombia and Peru, medication-related complications (side effects) and the presence of comorbidities concurrent with TB were highly common incidents that could provoke treatment withdrawal.20,21 Adverse reactions were also associated with having stopped treatment in a low incidence setting.22 Another common threat was missing follow-up visits. Factors related to this finding in other European cities were a lower perception of risk and suboptimal working conditions.15

Communication problems frequently occurred, due both to patients’ language barriers and to the complexity of healthcare-related information, which, as shown by the literature poses a major threat to adherence in different settings.23–25 Therefore, understanding health information is a requisite for correctly following treatment. Effective communication is essential for patients to take informed decisions and participate in health-promoting processes. As was already described among foreign-born TB patients in Barcelona,7 CHW strategy contributed to minimize this problem also for TB patients for this hospital. Another obstacle identified during TB treatment follow-up was traveling. Foreign-born move aboard more often than the Spanish-born population. Patients usually travel to their country of origin, which can lead to losses to follow-up and TB treatment discontinuation.26–28

Nevertheless, the most important data in our study were those related to the social discrimination affecting TB patients. These findings prompt reflection on the fact that, despite all the knowledge accumulated over the years, TB patients continue to experience perception of social rejection.16 Factors detected in this study were patients not mentioning their diagnosis to cohabitants or in the workplace, not accepting supervised treatment for fear of rejection in their environment, losing their Jobs or being at risk of having to change address because of their diagnosis. These factors directly impacted the therapeutic process and contact tracing. A study conducted in India, the country of origin of many of the patients in this study, supports this reflection and stresses that a substantial proportion of opinion leaders and social representatives show discriminatory behavior toward people who have had TB.29 Another study from Colombia revealed that health professionals, despite having sufficient knowledge of the disease, hold mistaken beliefs leading to discrimination against specific social groups.30 Among countries with a low TB burden, studies have been performed in the USA, Canada, the United Kingdom, Europe and Australia that mention the association between TB, stigma and immigrant communities and demonstrate the interaction between social and cultural determinants and stigma.31 Therefore, a negative social response to TB is universal. While global investigation is focused on treatment and diagnostic tools simplification, the available literature shows insufficient data on research, interventions and recommendations on this topic.32,33

Numerous strategies have been reported in the literature to enhance treatment adherence and contact tracing, including reminders and food vouchers, adherence agreements, intensive patient supervision and social support, the use of new technologies such as an ingestible sensor-based system, video-calls, video DOT etc., which seem to have some potential.34,35 However, broad consensus in the literature is reserved for multi-pronged approaches known as “intervention packages”. This approach is based on patients’ needs and is effective in enhancing adherence.5,36–41 The combined use of all the strategies employed in this study—follow-up calls and liaison between healthcare levels, medical and humanitarian reports, DOT, extra visits, cultural mediation and CHW—allowed completion of most anti-TB treatments and contact tracing. The work performed in a network consisting of healthcare and non-healthcare professionals was essential to carry out these activities. Among other elements, key factors configuring the strategy implemented by the Barcelona TB Program are TB units with nurse case managers, public health teams, DOT teams, CHW, primary care and methadone maintenance programs.7,42,43 As in other countries such as the United Kingdom, the cornerstones of this strategy are flexible healthcare, multidisciplinary teams, and the assignment of a health professional as a key worker to each patient with TB.44

This study found that, compared with Spanish-born, foreign-born patients showed a higher number of threats and incidents during treatment. However, foreign-born required more interventions and finally had similar treatment evolution than Spanish-born patients. Therefore, we can assume that the greater number of interventions in the group with more incidents would be the cause of the similar final evolution.

One of the strengths of this study is that it provides an overall view of the context of patients treated in a referral hospital in Barcelona. The Spanish health system provides universal and for-free coverage. Moreover, the Barcelona TB Program has broad experience and there is clear coordination between the various stakeholders involved in the management and control of TB. The study designed a specific data collection form, favoring rigor in registering data and coherence of the information. In addition, various data sources were used, ensuring the veracity of the data. On the other hand, this study has the limitations characteristic of observational designs such us little control of confounding factors. Moreover, under-registering of the activities reported by the professionals involved in patient follow-up was possible. Another limitation was the small number of cases, which did not allow for more complex statistical analyzes.

Identifying the context and incidents occurring during TB treatment allows the implementation of measures to enhance patients’ adherence. Moreover, coordinated interventions between professionals from different health fields allow to complete treatment: interventions aiming to reduce stigma, improve the administrative situation of the patients, and ensure adequate treatment during trips. The most effective strategy is combining a package of multidisciplinary interventions responding to the particular needs of each patient.

All authors were involved in the conception or design of the work; the acquisition, analysis and interpretation of data; the drafting of the work and revising it critically; the final approval; and agree to be accountable for all aspects of the work.

The authors declare that they have no competing interests.

No additional funding was required.

The project was approved by the Clinical Research Ethics Committee of Parc de Salut Mar (number 2014/5840/I).