Tuberculosis among children visiting friends & relatives

Abstract

Background

Most paediatric tuberculosis (TB) cases in low-TB-incidence countries involve children born to migrant families. This may be partially explained by trips to their countries of origin for visiting friends and relatives (VFR). We aimed to estimate the risk of latent TB infection (LTBI) and TB in children VFR.

Methods

We conducted a prospective multicentric observational study in Catalonia (Spain) from June 2017 to December 2019. We enrolled children aged < 15 years with a negative tuberculin skin test (TST) at baseline and at least one parent from a high-TB-incidence country, and who had travelled to their parent’s birth country for ≥21 days. TST and QuantiFERON-TB Gold Plus (QFT-Plus) were performed within 8–12 weeks post-return. LTBI was defined as a TST ≥5 mm and/or a positive QFT-Plus.

Results

Five hundred children completed the study, equivalent to 78.2 person-years of follow-up (PYFU). Thirteen children (2.6%) were diagnosed with LTBI (16.6/per100 PYFU, 95%CI = 8.8–28.5), including two cases (0.4%) of TB (2.5/per100 PYFU, 95%CI = 0.3–9.3). LTBI incidence rates remained high after excluding BCG-vaccinated children (9.7/per100 PYFU, 95%CI = 3.9–20.0). Household tobacco smoke exposure was associated with LTBI (aOR = 3.9, 95%CI = 1.1–13.3).

Conclusions

The risk of LTBI in children VFR in high-TB-incidence countries may equal, or perhaps even exceed, the infection risk of the native population. The primary associated risk factor was the presence of smokers in the household. Furthermore, the incidence rate of active TB largely surpassed that of the countries visited. Children VFR in high-TB-incidence countries should be targeted for diagnostic and preventive interventions.

Introduction

Mycobacterium tuberculosis infection affects approximately one-quarter of the global population, and a significant proportion (5–10%) of those infected develop tuberculosis (TB) during their lifetime. The highest risk of TB occurs within the first two years after infection.¹ Traditional TB control programmes have primarily focused on managing active TB cases and contact tracing. However, recent evidence has demonstrated that this approach alone is insufficient to achieve TB eradication. Consequently, there is a recognized need for a comprehensive strategy aimed at addressing latent tuberculosis infection (LTBI), which has been identified as a major target for TB control in the coming years.² Despite these efforts, national policies regarding LTBI management vary considerably, emphasizing the need for further evidence in this field to define the best control strategies.³

The burden of TB is higher among migrants compared to the populational average in high-income countries with a low TB incidence.⁴ This higher incidence often persists for several years following the migrants’ arrival in their destination country.⁵ This phenomenon may be attributed to socio-economic difficulties, overcrowding, migration stress, or a high TB incidence in their countries of origin.⁶ The World Health Organization END TB strategy emphasizes the importance of screening high-risk groups for LTBI and active TB in countries with a low TB incidence.⁷ Some studies have already suggested the effectiveness and cost-effectiveness of migrant-focused LTBI screening programmes.⁸

In the same sense, most new paediatric TB cases diagnosed in Canada, the United States, and the European Union involve migrant families, regardless of whether the child was born in the host country or not.⁹ Children are at a greater risk of developing active TB after primary infection, especially in those under 5 years of age. Moreover, children with LTBI can serve as a TB reservoir if preventive treatment is not administered. Therefore, diagnosing and managing LTBI in children is a critical TB control strategy.¹⁰

It has been estimated that international travel will reach approximately 1.8 billion by 2030.¹¹ Travellers visiting friends and relatives (VFRs) account for up to 50% of international travellers from high-income countries.¹² Travellers to countries with a high-TB incidence are at risk of acquiring LTBI and TB during travel.¹³ Travel-related factors, such as transmission intensity, stay duration, contact with the local population and individual characteristics, have been associated with TB transmission.¹³ To date, there is very little information regarding the relationship between VFR trips and TB¹³,and the heterogeneity within the VFR population poses challenges to studying this phenomenon.¹⁴ More data on the risk factors of LTBI and active TB in VFR travellers are needed to enhance health policies for TB control in low-incidence countries.¹³

This study aimed to investigate the conversion rate of TB immunodiagnostic tests, which serve as a surrogate diagnosis for LTBI, as well as the incidence rates of TB in a sizable cohort of children VFR. Additionally, we sought to identify risk factors associated with both incident LTBI and TB in this population.

Methods and design

This was a prospective, multicentric, observational study carried out in 5 pre-travel healthcare clinics and 21 primary healthcare centres in Catalonia (Spain) from June 2017 to December 2019 (Table 1). A detailed description of the study protocol was published previously.¹⁵ Trial registration: Clinical-Trials.gov: NCT04236765.

Table 1.

Study population and travel characteristics in a cohort of 500 children visiting friends and relatives

Individual characteristics
	Total cohort (n = 500)	%/IQR
Sex
Female	251	50.2
Male	249	49.8
Age (years)	6.9	4.0–9.8
0–4	167	33.4
5–9	217	43.4
10–14	116	23.2
Children’s birth country
Catalonia/Spain	461	92.2
Other countries	39	7.8
BCG Vaccinated*	36	7.2
Travel characteristics
Travel duration	1.2	1.0–1.8
Less than 1 month	163	32.6
1–3 months	306	61.2
>3 months	31	6.2
Continent travel destination
Africa	293	58.6
Asia	123	24.6
Latin America	71	14.2
Europe	13	2.6
TB incidence countries	590
40–99 TB cases*100 000 inhabitants	58	11.6
>99 TB cases*100 000 inhabitants	442	88.4
Household members (median)	7	5.0–9.0
0–4	49	9.8
5–9	318	63.6
≥ 10	99	19.8
Unknown	34	6.8
Smokers in host home
No	403	80.6
Yes	91	18.2
Unknown	6	1.2
Travel environment
Only Urban	233	46.6
Only Rural	188	37.6
Mixed	64	12.8
Others/unknown	15	3.0
Contact with suspected TB case
Yes	7	1.4
No	483	96.6
Unknown	10	2.0

Abbreviations: TB: Tuberculosis, BCG: Bacillus Calmette-Guérin, IQR: interquartile range

Setting and participants

The study enrolled children under 15 years of age who were migrants or born to a migrant family in the European Economic Area. The inclusion criteria were as follows: (1) having at least one parent from a high-TB incidence country (≥40 cases/100 000 inhabitants); (2) travelling for VFR for at least 21 days to the parent’s birth country; and (3) written informed consent from the parents or legal guardians. Participant selection was not based on the child’s country of birth, individual or familial characteristics, or travel destination.

The exclusion criteria were as follows: (1) previous diagnosis of LTBI or active TB; (2) travel for tourism purposes (defined as overnight stays in a hotel with no or minimal contact with the local population); and (3) significant previous disease as determined by the attending physician (i.e. congenital heart disease, cystic fibrosis, primary or secondary immunodeficiency, among others).

Based on the previously calculated sample size,¹⁵ we aimed to enrol 492 children to detect at least an increase from 0 to 2% in the proportion of incident LTBI cases.

Data collection and immunodiagnostic tests

At baseline, eligible children were identified and invited to participate. Demographic and clinical data were collected in a REDCap database hosted at the Fundació Docència i Recerca MútuaTerrassa. A tuberculin skin test (TST) was performed within 30 days before the trip. Children with a baseline TST result ≥5 mm were excluded from the study and managed as per local guidelines.¹⁶ A follow-up visit was conducted 8 to 12 weeks after their return from the VFR trip. During this visit, further epidemiological and clinical data were collected and both a TST and a QuantiFERON-TB Gold Plus test (QFT-Plus; Cellestis/Qiagen, Hilden, Germany) were performed the same day or, alternatively, within a maximum interval of 7 days. Children diagnosed with LTBI or active TB received appropriate treatment, and their relatives were referred to a specialized unit for contact tracing.¹⁶

TSTs were performed by intradermal injection of 0.1 mL (2 tuberculin units) of purified protein derivative (Tuberculin PPD RT23, Statens Serum Institut, Copenhagen, Denmark), and the results were read by trained personnel after 48–72 h. For the QFT-Plus test, a blood sample of 4 mL was collected, and the results were interpreted as per the manufacturer’s instructions.

Outcomes

The main outcome of the study was the diagnosis of LTBI or active TB following a VFR trip to a high-TB incidence country. Briefly, the diagnosis of active TB was based on epidemiological, clinical, radiological and microbiological findings according to published consensus criteria, irrespective of TST and QFT-Plus results.¹⁷ LTBI was defined as conversion to a positive TST (≥ 5 mm) and/or a QFT-Plus positive result in the absence of clinical signs or symptoms or radiological findings consistent with active TB in accordance with Spanish Guidelines.¹⁶ The Bacillus Calmette-Guérin (BCG) vaccine has not been included in the Catalan vaccination schedule since 1974.

Statistical analysis

Categorical variables were described using frequency tables, while continuous variables were reported as the median, mean and interquartile range (IQR). Paired proportions were used for comparisons. The incidence rates of LTBI and active TB were estimated per 100 person-year of follow-up (PYFU). To identify factors associated with the presence of LTBI and active TB, bivariate analyses were performed using the Fisher exact test or Chi-square test and the Mann–Whitney test, followed by conditional backward binary logistic regression analysis, with adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) calculated. The concordance between tests (TST and QFT-Plus) was measured using the Kappa index. Indeterminate QFT-Plus results were considered negative for this analysis. Alternative analyses using other TST cut-offs (≥ 10 mm and ≥ 15 mm) and excluding BCG-vaccinated patients were performed. The type I error was established at 5% and the type II error was set at 20%. The statistical analyses were performed using PASW Statistics 25 (SPSS Inc., Chicago, IL, USA).

Ethics

The study was approved by two clinical research ethics committees, that of the Hospital Universitari MútuaTerrassa on 24 February 2016 (ref 02/16) and the Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol-i-Gurina on 29 June 2016 (ref. P16/094). All parents or legal guardians received oral and written information about the study and written informed consent was obtained before inclusion.

Results

Children and travel characteristics at baseline

Out of the 622 children invited to participate, 23 declined to take part, and 9 of remaining 599 (1.5%) tested positive at baseline. Among the 590 children enrolled in the study, 90 did not complete the follow-up, due to either non-attendance to the post-travel medical visit or the unavailability of results from either of the immunodiagnostic assays (TST or QFT-Plus). Therefore, 500 children (50.2% were girls and the median age was 6.9 [IQR = 4.0–9.8] years old) completed the follow-up after the VFR trip and were included in the analysis, providing a cumulative follow-up period of 78.2 PYFU (Figure 1 and Table 1).

Figure 1.

Flowchart showing the patients invited to participate in the study, enrolled in the study and finally included in the analysis. Abbreviations: TST: Tuberculin Skin Test

Regarding the VFR trip, the countries most frequently visited were Morocco (50.8%), Pakistan (10.8%), India (7.2%), Bolivia (6.0%) and Bangladesh (4.0%) (Supplementary Table 1). Baseline TSTs were performed a medium of 14 days before travel (IQR = 8–22 days) and the median trip duration was 37 (IQR = 29–56) days. Regarding accommodation during the trip, 46.6 and 37.6% were exclusively in urban and rural areas, respectively; the median number of household members per host home was 7 (IQR = 5–9); and in 18.2% of cases, there were smokers in the host home. Post-travel assessments were performed 73 (IQR = 64–92) days after return from the trip, with TST and QFT-Plus being performed on the same day in 396 cases (79.2%), within 72 hours in 62 cases (12.4%) and within 7 days in the remaining 42 cases (8.4%). Only 1.4% of children reported contact with a suspected TB case during the VFR trip. Test conversion was observed in children VFR in Morocco (6/254 children; 2.4%), Bangladesh (4/20; 20.0%), Honduras (1/9; 11.1%), Romania (1/13; 7.7%) and India (1/36, 2.8%). None were from the same family.

Main outcomes

As per study definitions, 13 out of 500 children (2.6%; TST/QFT-Plus +/+ combination, n = 3; +/− combination, n = 9; and −/+ combination, n = 1) were diagnosed with M. tuberculosis infection. Of these, 11 were classified as LTBI, and 2 were diagnosed with active TB (Suppl. Table 2). The latter two were asymptomatic cases of primary pulmonary TB without microbiological confirmation, both of whom were successfully treated with a standard 6-month anti-TB regimen (cases 1 and 2 in Table 2). This translated into an incidence rate of 16.6 per 100 PYFU for LTBI and 2.6 per 100 PYFU for active TB. The remaining patients (n = 487) had a TST/QFT-Plus −/− combination, including five children with an indeterminate QFT-Plus result. Concordance between the tests was fair (98.0%; κ = 0.367, 95%CI = 0.065–0.669) (Suppl. Table 2).

Table 2.

Individual characteristics for tuberculosis infection diagnostic test converters

ID number	Age (years)	Gender	BCG vaccination	Country of birth	Travel destination	Travel duration (month)	Rural environment	Passive smoker	TST PRE-travel	TST POST-travel	QFT	Chest X-ray
1	1.8	Female	No	Spain	Morocco	2.4	Yes	Yes	0	22	Positive	Pulmonary primary TB
2	11.8	Male	No	Spain	Morocco	2.5	Yes	Yes	0	19	Positive	Pulmonary primary TB
3	10.0	Male	No	Spain	Morocco	1.5	Yes	Yes	0	18	Positive	No abnormalities
4	10.4	Male	Yes	Spain	Morocco	1.3	Yes	No	0	17	Negative	No abnormalities
5	14.9	Male	No	Spain	Morocco	1.4	No	No	0	15	Negative	No abnormalities
6	6.1	Male	Yes	Bangladesh	Bangladesh	1.2	No	No	0	14	Negative	No abnormalities
7	10.8	Male	Yes	Honduras	Honduras	1.4	Yes	No	0	9	Negative	No abnormalities
8	2.7	Female	No	Spain	India	2.2	No	No	0	8	Negative	No abnormalities
9	11.5	Male	Yes	Morocco	Morocco	1.1	No	No	0	8	Negative	No abnormalities
10	1.6	Male	No	Spain	Bangladesh	3.2	No	No	0	6	Negative	No abnormalities
11	14.9	Female	Yes	Bangladesh	Bangladesh	2.5	No	No	0	5	Negative	No abnormalities
12	13.0	Female	Yes	Bangladesh	Bangladesh	2.6	Yes	Yes	0	5	Negative	No abnormalities
13	3.2	Female	No	Spain	Rumania	0.7	No	Yes	0	0	Positive	No abnormalities

Abbreviations: TB: active tuberculosis, TST: Tuberculin Skin Test, QFT: QuantiFERON-TB plus, BCG: Bacillus Calmette-Guérin vaccine

In the multivariate analysis (Suppl. Table 3), the diagnosis of post travel LTBI was associated with the presence of smokers in the host home (aOR = 3.9, 95%CI = 1.1–13.3) and with BCG vaccination (aOR = 12.8, 95%CI = 3.7–45.1).

Sub-analysis at the 10- and 15-mm TST cut-offs

The incidence rates of LTBI according to the TST cut-offs of 10 and 15 mm were 9.0 per 100 PYFU and 7.7 per 100 PYFU, respectively. The incidence rate of active TB remained unchanged. The presence of household smokers remained independently associated with LTBI with the TST cut-offs of 10 and 15 mm (aOR = 6.1, 95%CI = 1.5–30.3 and aOR = 10.0, 95%CI = 1.8–55.6, respectively), but the effect of previous BCG vaccination was lost (Suppl. Table 3). The larger the TST cut-off, the higher the concordance between TST and QFT-Plus results, being 99.2% (κ = 0.596, 95%CI = 0.235–0.958) for the 10-mm cut-off and 99.4% (κ = 0.664, 95%CI = 0.306–1.000) for the 15-mm cut-off.

Sub-analysis excluding BCG-vaccinated patients

After excluding BCG-vaccinated patients (n = 464), the incidence rates of LTBI and active TB were 9.7 per 100 PYFU and 2.8 per 100 PYFU, respectively. The presence of household smokers remained independently associated with LTBI with the 5-, 10- and 15-mm TST cut-offs (aOR = 4.1, 95%CI = 1.0–16.9; aOR = 8.3, 95%CI = 1.5–46.3; and aOR = 16.7, 95%CI = 1.8–151.1, respectively). The concordance between the tests was moderate (99.0%; κ = 0.54, 95%CI = 0.18–0.90) (Suppl. Table 2).

Similar findings were observed in all the analyses in which VFR children travelling to Morocco (n = 246) were excluded (Suppl. Table 4).

Discussion

The results of this study, conducted in a prospective cohort of children VFR who travelled to regions with an intermediate to high incidence of TB, identified infection rates that closely correspond to the 5–10% annual risk of infection estimated for high-endemicity countries,¹⁸ when the most stringent diagnostic criteria are applied. The primary associated risk factor was the presence of smokers in the household. Furthermore, the incidence rate of active TB largely surpassed that of the countries visited.

These findings can be partially explained by two primary hypotheses. Firstly, the annual risk of LTBI in high burden-TB countries may be higher than expected, ranging between 5 and 10%, as recently reported.¹⁸ Secondly, paediatric VFR travellers may be more susceptible to LTBI or active TB due to a lower level of induced trained immunity against M. tuberculosis.¹⁹ This susceptibility could be attributed to lower coverage with BCG vaccination, especially among those born in the European Economic Area, and lower exposure to non-tuberculous mycobacteria in the countries in which they reside.²⁰

In most high-income low-TB-incidence countries, the majority of paediatric TB cases are diagnosed in children born to migrant families, regardless of whether the child was born in the parent’s country of origin or in the host country.⁹ This has mainly been attributed to worse socio-economic conditions and a higher TB incidence rate in their communities.⁶ Although several previous studies reported an increased risk of LTBI and active TB among individuals who travel to their home countries, with the use of a mathematical model, Koskal et al. established that VFR trips among the adult migrant population contribute to an increase in LTBI cases in the Netherlands. Nonetheless, this increase was of low significance in terms of the proportional number of cases.²¹ On the other hand, there are limited data specifically related to children. Two North American case–control studies comparing children with positive TST results to those with negative TST results identified VFR trips as a risk factor for LTBI.^22,23 In the same way as our study, a Canadian study conducted in British Columbia, which analysed 49 TB cases in children and used genotyping and whole-genome sequencing, found that almost half of the children born in Canada to foreign-born parents acquired their infections through travel to their parents’ place of birth.²⁴

According to data from 2017 to 2019 in Catalonia, 55.2% of TB cases occurred among migrants. The incidence rate among foreign-born migrant children was 16.1 per 100 000 inhabitants, whereas in the native Catalan paediatric population, it was 6.1 per 100 000 inhabitants.²⁵ In the latter group, nearly 50% of the cases were among children born to migrant families, resulting in an incidence rate of 9.7 in this group compared to 3.2 among Spanish-born children from non-migrant families. The most recent data on the risk of LTBI in Barcelona dates back to 1992 when they were less than 0.25%, with TB incidence rates of more than 60 per 100 000 inhabitants at that time (Data provided by the Department of Public Health of Catalonia).

In a meta-analysis conducted in individuals who had travelled to countries with a high TB incidence, including trips of up to 6 months, a pooled cumulative infection rate of 4.3% (95%CI = 2.8–6.7%) was observed among healthcare workers, being 1.6% (95%CI = 1.0–2.5%) among the rest of the travellers.^13,26

It is likely that VFR trips play a significant role in the epidemiological dynamics of TB in regions with a low incidence of TB because they contribute significantly to the continued high incidence of LTBI and active TB in migrant communities. As a high-risk group, paediatric VFR travellers should be targeted for preventive interventions, possibly along with their families, as they have likely been exposed to the same index case.⁷

The multivariate analysis of factors associated with the diagnosis of LTBI showed that only second-hand tobacco smoke exposure remained independently associated with a higher risk of LTBI in all sub-analyses, as reported previously.²⁷ It has been hypothesised that tobacco exposure increases the risk of infections by impairing immune defence mechanisms.²⁸ Interestingly, previous BCG vaccination was independently associated with LTBI only when the lower TST cut-off (5–9 mm) was used, suggesting that some of the cases identified in the present study were possibly due to false positive TST results because of a boosted response to BCG (after an initially negative TST in the pre-trip visit).²⁹ This significant effect was lost at TST cut-offs ≥10 mm, reinforcing the hypothesis of a true recent infection and the limited influence of a single BCG vaccine dose in the neonatal period on TST results.²² This finding also supports the 10-mm cut-off used for travellers in many guidelines.³⁰ Nevertheless, the clinical significance of the conversion of the TST result (from 0 to 5–9 mm induration) in a BCG-unvaccinated VFR child remains uncertain. While some authors advocate that interferon-gamma release assays should play a major role in confirming LTBI,³¹ in the present study, the concordance between TST and QFT-Plus results ranged from only fair at the 5-mm cut-off to good at the 15-mm cut-off. These results are consistent with previous studies in large cohorts of children at risk of TB.^32,33 Both TST and QFT-Plus are imperfect screening tests for LTBI, and discordant results should be interpreted taking into account the individual’s risk of infection and progression. Despite these diagnostic uncertainties, we strongly believe that if the TST result of any child has converted to positive or a positive interferon-gamma release assay is presented after a VFR trip to a high burden-TB country, the child should be evaluated to rule out TB and initiate appropriate LTBI therapy as per local guidelines.³⁴

The heterogeneous nature of the VFR population presents significant challenges that need to be considered. Variations in both individual characteristics (country of birth, country of residence and socio-economic status) and factors related to travel (the destination country or region, whether to urban or rural areas, overcrowding, weather conditions, household conditions or tobacco exposure) contribute to this diversity and hinder the investigation of LTBI in this particular population.¹³ For these reasons, effective implementation of public health strategy requires the involvement of primary healthcare services that are easily accessible to patients and capable of detecting VFR trips in addition to traveller medical services. This would enable the implementation of large-scale diagnostic and preventive strategies, such as LTBI screening or BCG vaccination.³⁵

Our study is limited by the absence of a universally agreed-upon gold standard diagnostic test for LTBI, which implies that alternative definitions of LTBI are conceivable but likely do not significantly alter the overall interpretation of the results. Despite the enrolment of nearly 600 paediatric participants, a potential lack of statistical power may have hindered the capacity to establish associations between LTBI risk and either the country’s incidence rates or the duration of travel. It is noteworthy that systematic reviews focused on international travellers also failed to elucidate such associations.¹³ Another significant limitation noted after examining the results is that travel durations shorter than 21 days were not included, and it is likely that these trips also have a remarkable risk of contagion. In addition, we established a 21-day minimum stay to align with the work vacation period in Spain and to optimize the recruitment process. Longer minimum sojourns are advocated by other guidelines,³⁰ albeit arbitrarily. Another potential limitation of the study is the lack of information on the length of time foreign-born children had spent in the country of origin before migration, although this only affected 7.8% of the sample. These data were not available, but it should be kept in mind that all the children studied had a negative pre-travel TST. Half of the children in our study travelled to Morocco, reflecting the Catalan socio-demographic reality in terms of the migrant population. VFR trips from Catalonia to Morocco are very common due to the geographic proximity and affordable land transportation. While this could represent a bias, the main findings remained unchanged when Moroccan children were excluded from the analyses. Finally, possible infection of the child before the pre-trip visit, with TST conversion taking place during the trip, cannot be ruled out.

In summary, trips for VFR are common among migrant families and their descendants. The risk of LTBI in children VFR may equal, or perhaps even exceed, the infection risk of the native population in countries with high and intermediate TB incidence rates. The findings of this study suggest that specific public health measures should be taken to prevent TB in paediatric VFR travellers and to potentially limit the impact of the VFR phenomenon on the dynamics of TB in low-endemic countries. Further studies on VFR population are necessary not only in relation to TB but also regarding exposure to additional health risks for which very little data are available.

Funding

This work was partially supported by a research grant from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), awarded on the 2016 call under the Health Strategy Action 2013–2016, within the National Research Program oriented to Societal Challenges, within the Technical, Scientific and Innovation Research National Plan 2013–2016, with reference PI16/00314 and PI22/00766, co-funded with European Union ERDF funds (European Regional Development Fund); by the Departament de Salut of the Generalitat de Catalunya, in the call Pla Estratègic de Recerca i Innovació en Salut (PERIS) 2016–2020, code SLT006/17/144; by the Spanish Society of Pneumology and Thoracic Surgery (grant number 90/2015 and 169-2022) and Research Foundation MutuaTerrassa in the call Primary Health research projects 2017. The funders had no authority over any of the activities of the project.

Conflict of interest: None declared.

Data availability

Primary data from this study is available from the authors upon reasonable request. Requests will be reviewed and authorized by the Biomedical Research Ethics Committee of the Mútua Terrassa Healthcare Foundation (ceim@mutuaterrassa.cat).