The epidemiology of Chagas disease, until recently confined to areas of continental Latin America, has undergone considerable changes in recent decades due to migration to other parts of the world, including Spain. We studied the prevalence of Chagas disease in Latin American patients treated at a health center in Barcelona and evaluated its clinical phase. We make some recommendations for screening for the disease.
We performed an observational, cross-sectional prevalence study by means of an immunochromatographic test screening of all continental Latin American patients over the age of 14 years visiting the health centre from October 2007 to October 2009. The diagnosis was confirmed by serological methods: conventional in-house ELISA (cELISA), a commercial kit (rELISA) and ELISA using T cruzi lysate (Ortho-Clinical Diagnostics) (oELISA). Of 766 patients studied, 22 were diagnosed with T. cruzi infection, showing a prevalence of 2.87% (95% CI, 1.6–4.12%). Of the infected patients, 45.45% men and 54.55% women, 21 were from Bolivia, showing a prevalence in the Bolivian subgroup (n = 127) of 16.53% (95% CI, 9.6–23.39%).
All the infected patients were in a chronic phase of Chagas disease: 81% with the indeterminate form, 9.5% with the cardiac form and 9.5% with the cardiodigestive form. All patients infected with T. cruzi had heard of Chagas disease in their country of origin, 82% knew someone affected, and 77% had a significant history of living in adobe houses in rural areas.
We found a high prevalence of T. cruzi infection in immigrants from Bolivia. Detection of T. cruzi–infected persons by screening programs in non-endemic countries would control non-vectorial transmission and would benefit the persons affected, public health and national health systems.
Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi, and is becoming an emerging health problem in non-endemic areas because of growing population movements. The clinical manifestations of chronic T. cruzi infection include the latent form (the indeterminate chronic form), the cardiac form, the digestive or cardiodigestive form, and sudden death. Therefore, many diagnoses of Chagas disease are based on epidemiological suspicion rather than on clinical signs and symptoms. This study showed that the prevalence of Chagas disease in Latin American patients attending at a health center in Barcelona is 2,87% and the highest prevalence was found among Bolivian patients (16,53%). All the infected patients were in a chronic phase of Chagas disease. Detection of T. cruzi–infected persons by screening programs in non-endemic countries would control non-vectorial transmission and would benefit the persons affected, public health and national health systems. The data obtained in this study and the experiences described elsewhere suggest that it is advisable to perform Chagas disease screening in non-endemic countries on all patients from continental Latin America who: (1)have a suggestive epidemiologic history, (2)are pregnant, (3)are immunosuppressed, (4)have symptoms suggestive of Chagas disease, or (5)request screening.
Citation: Roca C, Pinazo MJ, López-Chejade P, Bayó J, Posada E, López-Solana J, et al. (2011) Chagas Disease among the Latin American Adult Population Attending in a Primary Care Center in Barcelona, Spain. PLoS Negl Trop Dis 5(4): e1135. doi:10.1371/journal.pntd.0001135
Editor: Helton da Costa Santiago, National Institutes of Health, United States of America
Received: November 6, 2010; Accepted: February 14, 2011; Published: April 26, 2011
Copyright: © 2011 Roca et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The study was funded by the Catalan Society for Family and Community Medicine (8th call, 2007) and Àmbit Barcelona Ciutat-Institut Català de la Salut. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Trypanosoma cruzi (T. cruzi) is a flagellate protozoan that causes Chagas disease (CD). It is traditionally linked to rural areas of continental Latin America, where it is transmitted by a variety of bug vectors. In recent decades, the epidemiological pattern of this disease has undergone considerable changes . In the endemic countries of Latin America, the regional Chagas programs are working to interrupt vector-borne and transfusional transmission, to control congenital Chagas disease and to support initiatives aimed at improving diagnosis, management and surveillance of the disease . In non-endemic countries that receive immigrants from Latin America or send tourists to endemic areas, CD is an emerging disease and has become a public health problem because it can be transmitted by non-vectorial mechanisms , .
Spain is a major European host country for people from Latin America. According to the Spanish National Institute of Statistics, in 2009 more than 1.8 million immigrants from Latin America were registered, accounting for 3.85% of the total population . In recent years several studies of CD in non-endemic countries – have focused in particular on non-vectorial transmission mechanisms such as pregnancy and childbirth , , blood transfusion ,  and organ transplantation , . However, when reviewing the literature we found little information on imported CD in non-endemic countries at the primary care level , which is ideal for screening the general population .
The clinical manifestations of chronic T. cruzi infection include the latent form (the indeterminate chronic form), which occurs in 60% of cases , the cardiac form , the digestive or cardiodigestive form, and sudden death . Therefore, many diagnoses of CD are based on epidemiological suspicion rather than clinical signs and symptoms.
The objectives of the present study were (1) to assess the prevalence of Trypanosoma cruzi infection in the adult Latin American population treated at a health center in Barcelona, Spain; (2) to analyze the clinical phase of the disease; and (3) to determine whether screening for imported CD in primary care should be recommended.
Study design and scope
We performed an observational, cross-sectional prevalence study at the health center of the Clot district, Barcelona. This center serves a population of 25442 people, with a total foreign population of 13.5% and a Latin American population of 6.3% (according to the 2008 census of the Barcelona City Council) . The staffs participating in the study were 14 general practitioners, 13 nurses, 1 gynecologist and 1 midwife.
The study protocol was approved by the Ethical Committee of the Jordi Gol Institute for Research in Primary Care of the Institut Català de la Salut (Catalan Health Institute).
Written informed consent was requested from all participants. When participants were children, their parents/guardians provided informed consent.
During the period October 2007 to October 2009, all patients from continental Latin America under 14 years of age who presented at the health center for any health reason were invited to participate in the study. After obtaining informed consent, we collected clinical and epidemiological data.
We ascertained the reasons why the patients visited their doctor/nurse by reviewing the electronic patient charts. On a patient's first visit to a primary care centre the Preventive Activities and Health Promotion Program (PAPPS) is initiated , and at the Clot health center this program included CD screening of all persons originating from continental Latin America.
Serological screening was performed with an immunochromatographic test (ICT) that uses recombinant antigens of T. cruzi (TcD, TcE, PEP-2 and SAPA) on whole blood collected by finger prick.
If the screening was positive, a venous blood sample was collected to confirm the diagnosis at the Parasitology Laboratory of the Faculty of Pharmacy, University of Barcelona. We used 2 enzyme-linked immunosorbent assay (ELISA) methods: a conventional, in-house ELISA (cELISA) with whole T. cruzi epimastigote antigens  and a commercial kit with the recombinant antigens TcD, TcE, PEP-2 and TcLo1.2 (rELISA).
In accordance with international criteria established by the World Health Organization, sera that were reactive in two serological methods were considered positive . Positive results were confirmed by a third ELISA using T cruzi lysate (Ortho-Clinical Diagnostics) (oELISA). In a subsample of 101 patients we performed the ELISA serologies (cELISA and rELISA) regardless of the result of the ICT, in order to test the usefulness of this test in screening for CD in primary care .
Management of patients
All patients infected with T. cruzi were referred to the Tropical Medicine Unit of Hospital Clínic de Barcelona and clinically evaluated by a complete review of the epidemiologic history and consistent symptoms/signs, a general physical examination and an electrocardiogram. If the electrocardiogram was pathologic, it was assessed with an echocardiogram or 24-hour Holter according to the disease detected. If symptoms consistent with gastrointestinal involvement were detected , an esophageal, gastric and duodenal transit assessment or a barium enema was performed. Benznidazole (5 mg/kg/day for 60 days) was offered to all patients aged 18–50 years without advanced Chagas cardiomyopathy and no other contraindication for start benznidazole (pregnancy, severe renal or hepatic insufficiency . None of them refused to start it.
The sample size was calculated for an alpha level of 0.05 and a precision of ±0.05% in a bilateral comparison, assuming maximum uncertainty (50% prevalence); for a population of 1516 subjects  a random sample of 758 was necessary.
The programs SPSS version 17.0 and Epidat version 3.1 were used for the statistical analysis. The χ2 test was used to compare hypotheses of independence between two categorical variables and the Student t test for continuous variables. The confidence interval for all hypothesis comparisons was 95% and the tests were 2-tailed.
Of the 766 patients analyzed, 27 were reactive to the ICT and 20 of these were reactive in cELISA, rELISA and oELISA. Also, 2 patients of the 101 tested by ICT, cELISA, and rELISa regardless of the result of the first were reactive in cELISA and rELISA. Both were also positive in oELISA, so they were considered positive.
A total of 22 patients were diagnosed with CD, corresponding to a prevalence of 2.87% (95% CI, 1.6–4.12%) in the sample studied. Of these, 21 were from Bolivia; the prevalence of CD in the subgroup of Bolivian patients studied (n = 127) was 16.53% (95% CI, 9.6–23.39%). The remaining patient was from Paraguay.
All the patients infected by T. cruzi were in the chronic phase of CD. The clinical form and the reasons why they visited the health center are presented in Table 3. Four patients (18.2%) had been previously diagnosed in the country of origin, but none of them mentioned it in the primary care visit because they thought it was a health problem proper to their country that would be unknown to the Spanish health staff (this information was obtained when they were asked for informed consent to participate in the study). None of them were aware of their clinical phase and 2 patients had received incomplete treatment.
The prevalence of T. cruzi infection in the sample studied was 2.87% and in the subgroup of Bolivian patients it was 16.53%. In the medical literature we found few studies of similar characteristics to ours (involving screening of the adult Latin American population in primary care) and their results varied ,  due to the heterogeneity of the populations analyzed and the distribution of CD in Latin America.
The laboratory confirmation of a clinical suspicion of CD is based on consistent results of at least 2 different immunological tests . ICTs are attractive in primary care because they are easy to use in routine clinical practice and do not require sophisticated facilities or specialized staff. In the substudy that we performed in 101 patients , for the ICT used we found a sensitivity of 92.5% and a specificity of 96.8%. Other studies have evaluated the sensitivity and specificity of ICTs ,  with similar results. The current sensitivity of ICTs must be increased so that they can be used as effective screening tests. Meanwhile, they should be combined with other methods that offer greater sensitivity , .
The highest prevalence was found among Bolivian patients, in agreement with other studies performed in Spain ,  and other non-endemic countries , . No cases were diagnosed among the Peruvian or Ecuadorian patients, who formed 45% of the sample, probably due to the heterogeneous distribution of CD in endemic countries and the lower seroprevalence of T. cruzi estimated in Peru (0.69%) and Ecuador (1.74%) .
An epidemiologic history of having lived in rural areas and/or adobe houses showed a significant relationship with T. cruzi infection, consistent with the dominant vector-borne transmission mechanism in the countries of origin. All patients with T. cruzi infection had heard of CD in their countries of origin and approximately 82% knew someone who was affected. These data should be taken into account for establishing CD screening criteria in immigrants from endemic zones, because mere knowledge of the disease may be considered as an indirect indicator of its presence in the region of origin.
In non-endemic countries CD screening programs have been aimed at particularly susceptible groups: in blood banks (France , the USA  and Spain ), and in pregnant Latin American women and their neonates (the Spanish autonomous communities of Catalonia  and Valencia ). In our study only 9.5% of the patients with T. cruzi infection had visited the health center due to clinical symptoms suggestive of CD. As it is a silent disease that has recently appeared in non-endemic countries, we stress the importance of establishing in these countries health screening programs based on compatible epidemiologic history among the general immigrant population from endemic areas. These programs should be multidisciplinary , supported by the best scientific evidence possible, and promoted by the health authorities.
In non-endemic countries, detecting persons infected by T. cruzi is important in order to control the transmission (vertical, by transfusion, or by organ transplant), reduce reactivations in immunodepressed persons, and delay the onset of the chronic cardiac form through antiparasite treatment , all of which have a great impact on the persons affected, on public health, and on health systems. Nevertheless, the best solution for CD is a combination of treatment and prevention in endemic countries , , where many programs and initiatives are underway , .
The data obtained in this study and the experiences described elsewhere , , , , ,  suggest that it is advisable to perform CD screening in non-endemic countries on all patients from continental Latin America who: (1) have a suggestive epidemiologic history (having lived in a rural area, in adobe houses or having knowledge of CD in the country of origin), (2) are pregnant, (3) are immunosuppressed, (4) have symptoms suggestive of CD, or (5) request screening.
We thank OPERON S.A. for the disinterested supply of the ICTs. We also thank Silvia Tebar, Antoni Soriano and Lluís Valerio for their collaboration.
Chagas-Clot research group
Physicians: Ignacio Aoiz Linares, Isabel Arias Moliz, Joan Bayó Llibre, Marta Buela, Francesc-Xavier Cano Sana, Ester Casajuana Brunet, Josefina Filomena, Sarai de la Fuente Gilabert, Francisco-Javier García-Alfaro, Carlos Gonzalvo Orero, Laura Haro, MCarmen Igualada Delgado, Fernando Martín González, Elena Mellado, Itsaso Mendizábal Condon, Verónica Moldón, Melania Priego, Ricard Riel Cabrera, Carme Roca Saumell, Núria Sellarés, Rosa Senán Sanz, Mireia Ventura Fontanet, Nieves Vizcay Guruchaga, Josep Lluís Abad Rodríguez, Manel Honrado. Nurses: Teresa Areny Ribera, Gloria Camacho García, Consuelo Cantalapiedra Caicedo, Florencio Cardosa Oliver, Monica Espelt, M.Isabel Fernández Fraga, Josep Manel Grau Granero, Jordi López-Solana, M.Concepción López–Navarro, Esther Montero Moya, Anna Parcerisa Miralles, Marineus Puig García, Gloria Rosillo Sanz, Anna Urpí Fernández, M.José Lapuerta. Clinical assistants: Lurdes Martínez-Vidal, Rosa Fernández. Health Technicians: Josep Maria Escribà Jordana, Isabel Plaza Espuña.
Conceived and designed the experiments: CR JG MP. Performed the experiments: CR MJP JB JL-S EP Chagas-Clot Research Group. Analyzed the data: CR MJP JB MG MP JG. Contributed reagents/materials/analysis tools: PL-C MG MP. Wrote the paper: CR JG MP MG MJP JB.
- 1. Briceño-Leon R (2009) Chagas disease in the Americas: an ecohealth perspective. Cad Saúde Pública, Rio de Janeiro 25: S71–S82.
- 2. Pan American Health OrganizationPrograma Regional de Chagas de la OPS. Available: http://www.paho.org/spanish/ad/dpc/cd/dch-program-page.htm Accessed 28 April 2011.
- 3. Jackson Y, Angheben A, Carrilero Fernandez B, Jansà i López del Vallado JM, Jannin JG, et al. (2009) Prise en charge de la maladie de Chagas en Europe. Expériences et défis en Espagne, Suisse et Italie. Bull Soc Pathol Exot 102: 326–329.
- 4. Gascón J, Pinazo MJ (2008) Control de la transmisión vertical de Trypanosoma cruzi en España: principal reto de la patología importada. Enferm Infecc Microbiol Clin 26: 605–6.
- 5. Instituto Nacional de Estadística, España. Available: http://www.ine.es. Accessed 2010 May 26.
- 6. Gascón J, Bern C, Pinazo MJ (2010) Chagas disease in Spain, the United States and other non-endemic countries. Acta Trop 115: 22–27.
- 7. Develoux M, Lescure FX, Jaureguiberry S, Jeannel D, Elghouzzi MH, et al. (2010) Emergence of Chagas' disease in Europe: description of the first cases observed in Latin American immigrants in mainland France. Med Trop (Mars) 70: 38–42.
- 8. Guerri-Guttenberg RA, Ciannameo A, Di Girolamo C, Milei JJ (2009) Chagas disease: an emerging public health problem in Italy?. Infez Med 17: 5–13.
- 9. Muñoz J, Gómez i Prat J, Gállego M, Gimeno F, Treviño B, et al. (2009) Clinical profile of Trypanosoma cruzi infection in a non-endemic setting: immigration and Chagas disease in Barcelona (Spain). Acta Trop 111: 51–5.
- 10. Muñoz J, Coll O, Juncosa T, Vergés M, del Pino M, et al. (2009) Prevalence and vertical transmission of Trypanosoma cruzi infections among pregnant Latin American women attending 2 maternity clinics in Barcelona, Spain. Clin Infect Dis 8: 1736–40.
- 11. Lucas RM, Barba MC (2009) Prevalence of American trypanosomiasis in pregnant women from a health area of Valencia, Spain: 2005–2007. Rev Esp Salud Publica 83: 543–55.
- 12. Jackson Y, Gétaz L, Wolff H, Holst M, Mauris A, et al. (2010) Prevalence, clinical staging and risk for blood-borne transmission of Chagas disease among Latin American migrants in Geneva, Switzerland. PLoS Negl Trop Dis 4: e592.
- 13. Pirón M, Vergés M, Muñoz J, Casamitjana N, Sanz S, et al. (2008) Seroprevalence of Trypanosoma cruzi infection in at-risk blood donors in Catalonia (Spain). Transfusion 48: 1862–8.
- 14. Kun H, Moore A, Mascola L, Steurer F, Lawrence G, et al. (2009) Transmission of Trypanosoma cruzi by heart transplantation. Clin Infect Dis 48: 1534–40.
- 15. Nowicki MJ, Chinchilla C, Corado L, Matsuoka L, Selby R, et al. (2006) Prevalence of antibodies to Trypanosoma cruzi among solid organ donors in Southern California: a population at risk. Transplantation 81: 477–479.
- 16. Soriano Arandes A, Muñoz Gutierrez J, Vergés Navarro M, Castells Doménech C, Portus Vinyeta M, et al. (2009) Prevalence of Chagas disease in the Latin American immigrant population in a primary health centre in Barcelona (Spain). Acta Trop 112: 228–230.
- 17. Walley J, Lawn JE, Tinker A, de Francisco A, Chopra M, et al. (2008) Primary health care: making Alma-Ata a reality. Lancet 372: 1001–7.
- 18. Gascón J, en representación del Grupo de Trabajo del Taller “Enfermedad de Chagas importada: ¿un Nuevo reto de Salud Pública? (2005) Diagnóstico y tratamiento de la Enfermedad de Chagas importada. Med Clin (Barc.) 125: 230–5.
- 19. Gascón J, Albar P, Cañas E, Flores M, Gómez i Prat J, et al. (2007) Diagnóstico, manejo y tratamiento de la cardiopatía chagásica crónica en áreas donde la infección por Trypanosoma cruzi no es endémica. Rev Esp Cardiol 60: 285–93.
- 20. Rassi A, Rassi A, Marín-Neto JA (2010) Chagas disease. Lancet 375: 1388–1402.
- 21. Census of the Barcelona City Council Available: http://www.bcn.es/estadistica/catala/dades/index.htm. Accessed 2010 Mar 30.
- 22. Programa de Actividades Preventivas y de Promoción de la Salud Available: http://www.papps.org/. Accessed 2010 May 31.
- 23. Riera C, Vergés M, López-Chejade P, Pirón M, Gascón J, et al. (2009) Desarrollo y evaluación de una técnica ELISA con antígeno crudo de Trypanosoma cruzi para el diagnóstico de la efermedad de Chagas. Enf Emerg 11: 22–9.
- 24. WHO (2002) Control of Chagas disease. 2nd report of the World Health Organization Expert Committee. WHO Technical Report Series 905: 1–101.
- 25. López-Chejade P, Roca C, Posada E, Pinazo MJ, Gascón J, et al. (2010) Utilidad de un test inmunocromatográfico para el cribado de la enfermedad de Chagas en asistencia primaria. Enferm Infecc Microbiol Clín 28: 169–71.
- 26. Pinazo MJ, Cañas E, Elizalde JI, García M, Gascón J, et al. (2010) Diagnosis, management and treatment of chronic Chagas' gastrointestinal disease in areas where Trypanosoma cruzi infection is not endemic. Gastroenterol Hepatol 33: 191–200.
- 27. Bern C, Montgomery SP, Herwaldt BL, Rassi A, Marin-Neto JA, et al. (2007) Evaluation and Treatment of Chagas Disease in the United States: A Systematic Review. JAMA 298: 2171–2181.
- 28. Padrón municipal de habitantes. Institut Municipal d'Estadística. Ayuntamiento de Barcelona (2005) ABS 10G El Clot: equivalencia exacta con las zonas estadísticas de búsqueda 234 y 240 del Ayuntamiento de Barcelona.
- 29. Steele LS, MacPherson DW, Kim J, Keystone JS, Gushulak BD (2007) The sero-prevalence of antibodies to Trypanosoma cruzi in Latin American refugees and immigrants to Canada. J Immigr Minor Health 9: 43–7.
- 30. Roddy P, Goiri J, Flevaud L, Palma PP, Morote S, et al. (2008) Field evaluation of a rapid immunochromatographic assay for detection of Trypanosoma cruzi infection by use of whole blood. J Clin Microbiol 46: 2022–7.
- 31. Flores-Chávez M, Cruz I, Rodríguez M, Nieto J, Franco E, et al. (2010) Comparación de técnicas serológicas convencionales y no convencionales para el diagnóstico de la enfermedad de Chagas importada en España. Enferm Infecc Microbiol Clin 28: 284–293.
- 32. Lescure FX, Canestri A, Melliez H, Jauréguiberry S, Develoux M, et al. (2008) Chagas disease, France. Emerg Infect Dis 14: 644–646.
- 33. Bern C, Montgomery SP (2009) An estimate of the Burden of Chagas Disease in the United States. Clin Infect Dis 49: e52–e54.
- 34. El Ghouzzi MH, Boiret E, Wind F, Brochard C, Fittere S, et al. (2010) Testing blood donors for Chagas disease in the Paris area, France: first results after 18 months of screening. Transfusion 50: 575–83.
- 35. Bern C, Montgomery SP, Katz L, Caglioti S, Stramer SL (2008) Chagas disease and the US blood supply. Curr Opin Infect Dis 21: 476–82.
- 36. Ministerio de Sanidad y Consumo. España. Real Decreto sobre hemodonación (Real Decreto 1088/2005). Boletín Oficial del Estado. Available: http://www.boe.es/boe/dias/2005/09/20/pdfs/A31288-31304.pdf. Accessed 2010 Sept 01.
- 37. Departament de Salut, Generalitat de Catalunya. Protocol de cribatge i diagnòstic de malaltia de Chagas en dones embarassades llatinoamericanes i en els seus nadons. Available: http://www.gencat.cat/salut/depsalut/html/ca/dir2384/protchagas2010.pdf. Accessed 2010 Sept 01.
- 38. Conselleria de Salut, Comunitat Valenciana. Enfermedad de Chagas importada. Protocolo de actuación en la Comunitat Valenciana. Available: http://www.matronas-cv.org/categorias-principales/documentos/profesionales/i/475/65/enfermedad-de-chagas-importada-protocolo-de-actuacion-en-la-comunitat-valenciana Accessed 2010 Sept 01.
- 39. Viotti R, Vigliano C, Armenti A (2009) Nothing Goes on Forever… Chagas Disease. Rev Esp Cardiol 62: 1332–44.
- 40. Maguire JH (2006) Chagas' Disease – Can we stop the deaths? N Engl J Med 355: 760–761.
- 41. WHO 2010.Chagas disease: control and elimination. Report by the Secretariat. Available: http://apps.who.int/gb/ebwha/pdf_files/WHA63/A63_17-en.pdf. Accessed 2010 Sept 02.
- 42. Ponce C (2007) Current situation of Chagas disease in Central America. Mem Inst Oswaldo Cruz 102: 41–44.