María Jesús Pinazo

Clinical profile of Trypanosoma cruzi infection in a non-endemic setting: Immigration and Chagas disease in Barcelona (Spain)

BACKGROUNDnChagas disease is no longer limited to Latin America and is becoming frequent in industrialised countries in Europe and United States.nnnMETHODSnA descriptive study of Latin American immigrants in Barcelona attending two centres for imported diseases during a period of 3 years. The main outcome was the identification of Trypanosoma cruzi-infected individuals in a non-endemic country and the characterization of their clinical and epidemiological features.nnnRESULTSnA total of 489 Latin American patients participated in the study. Forty-one percent were infected by T. cruzi, and the most frequent country of origin was Bolivia. All T. cruzi infected patients were in chronic stages of infection. 19% of cases had cardiac disorders and 9% had digestive disorders.nnnCONCLUSIONSnA high percentage of participants in this study were infected by T. cruzi and various factors were found to be associated to the infection. It is important to improve clinical and epidemiological knowledge of T. cruzi infection in non-endemic countries and to develop appropriate screening and treatment protocols in these settings.

Economic evaluation of Chagas disease screening of pregnant Latin American women and of their infants in a non endemic area

Migration is a channel through which Chagas disease is imported, and vertical transmission is a channel through which the disease is spread in non-endemic countries. This study presents the economic evaluation of Chagas disease screening in pregnant women from Latin America and in their newborns in a non endemic area such as Spain. The economic impact of Chagas disease screening is tested through two decision models, one for the newborn and one for the mother, against the alternative hypothesis of no screening for either the newborn or the mother. Results show that the option no test is dominated by the option test. The cost effectiveness ratio in the newborn model was 22€/QALYs gained in the case of screening and 125€/QALYs gained in the case of no screening. The cost effectiveness ratio in the mother model was 96€/QALYs gained in the case of screening and 1675€/QALYs gained in the case of no screening. Probabilistic sensitivity analysis highlighted the reduction of uncertainty in the screening option. Threshold analysis assessed that even with a drop in Chagas prevalence from 3.4% to 0.9%, a drop in the probability of vertical transmission from 7.3% to 2.24% and with an increase of screening costs up to €37.5, test option would still be preferred to no test. The current study proved Chagas screening of all Latin American women giving birth in Spain and of their infants to be the best strategy compared to the non-screening option and provides useful information for health policy makers in their decision making process.

Chagas Disease among the Latin American Adult Population Attending in a Primary Care Center in Barcelona, Spain

Background/Aims 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. Methodology/Principal Findings 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 (nu200a=u200a127) 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. Conclusions 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.

The BENEFIT Trial: Where Do We Go from Here?

In the next five years, we can now project that 200,000 people living with Chagas disease will die from heart disease and related complications. We urgently need to redouble our efforts to identify and treat young people who are still in the early stages of their illness, but ultimately we need to find better treatments and new cures. n nAccording to recent estimates, there are 5.7–9.4 million people living with Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi), a neglected tropical disease and leading cause of heart disease and cardiomyopathy, especially in Latin America and the United States [1,2]. Today, less than 1% of people infected with T. cruzi have access to diagnosis and treatment [3], a consequence of the fact that Chagas disease mostly affects those living in extreme poverty and in marginal surroundings. This finding is especially sad given new information by the World Health Organization (WHO) stating that more than one-half of Chagas disease sufferers live in Latin America’s three wealthiest countries—Argentina, Brazil, and Mexico [1]. Moreover, there are hundreds of thousands of infected people living in the US, with emerging evidence for significant T. cruzi transmission in Texas [4,5]. In this sense, Chagas disease represents one of the Western Hemisphere’s greatest health disparities. Moreover, in recent years we also have seen the globalization of Chagas disease to Spain and elsewhere in Europe and worldwide [6]. n nFor years, the community of scientists, physicians, and other health care providers and Chagas disease patients has been awaiting the results of the Benznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial, which was designed to evaluate the safety and efficacy of benznidazole in patients with Chagasic cardiomyopathy [7]. Approximately 20%–30% of T. cruzi-infected individuals progress to Chagasic cardiomyopathy, a debilitating heart condition associated with conduction disturbances, heart failure, and sudden death. While it is established that benznidazole is effective in curing Chagas disease patients during their early acute phase [8–11], very few individuals are diagnosed at this stage of the disease. The BENEFIT trial aimed to determine if the 1.17 million people now living with Chagasic cardiomyopathy (WHO estimate [1]) might also experience improved clinical outcomes or even cures with benzimidazole treatment. n nUnfortunately, the answer appears to be “no.” Compared to a placebo control, benznidazole did not result in a statistically significant improvement in cardiac clinical outcomes. Although the study was not sufficiently powered to show incremental benefits in cardiac outcome (on the order of 5%–15%), it is clear that our current strategies for antiparasitic chemotherapy need to be revisited for patients with evidence of Chagasic heart disease. n nBut there is additional bad news—the BENEFIT trial found that in both treated and placebo arms (comprising almost three thousand patients), 17%–18% died over a five-year time frame, most from cardiac complications [7]. If we extrapolate from the WHO estimate, this means that roughly 200,000 people will die from Chagasic cardiomyopathy over the next five years. To put this number in perspective, it is almost identical to the number of women living in the US who will die from breast cancer over the same period [12]. n nWhereas breast cancer is now linked with a highly successfully and accomplished advocacy and awareness campaign that promotes early detection and treatment, as well as research and development (R&D) into an exciting portfolio of new and innovative therapies, we are now facing almost the opposite situation with Chagas disease and cardiomyopathy. Today, there are few advocates for the millions of Chagas disease sufferers mostly living in poor and marginalized conditions. As a result, the vast majority have no access to diagnosis and treatment, and far too little is invested into R&D for new drugs, vaccines, and other tools (including tests for cure). n nFrom our perspective, the BENEFIT trial is a wake-up call to aggressively pursue a global initiative of diagnosis, treatment, and research, emphasizing the following specific points:

Diagnosis, management and treatment of chronic Chagas’ gastrointestinal disease in areas where Trypanosoma cruzi infection is not endemic

Seccion de Medicina Tropical, Centro de Salud Internacional, Hospital Cĺinic i Provincial, Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Barcelona, Espana Consulta de Salud Internacional, Servicio de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocio, Sevilla, Espana Servicio de Gastroenteroloǵia, Hospital Cĺinic i Provincial, Barcelona, Espana Unidad de Salud Internacional, Hospital General de Valencia, Valencia, Espana Servicio de Radiodiagnostico, CDIC, Hospital Cĺinic i Provincial, Barcelona, Espana Unitat de Medicina Tropical i Salut Internacional Drassanes, Institut Catal a de la Salut (ICS), Barcelona, Espana Centro de Investigaciones en Microbioloǵia y Parasitoloǵia Tropical, Facultad de Ciencias, Departamento de Ciencias Biologicas, Universidad de los Andes, Bogot a, Colombia Gastroenteroloǵia, Hospital La Fe, Valencia, Espana Seccion de Medicina Tropical, Hospital Carlos III, Madrid, Espana Instituto de Gastroenteroloǵia de la Goiânia, Universidad Federal de Goi as, Goiânia, Goias, Brazil Unidad de Medicina Tropical de Hospital de Poniente, Aguadulce (Almeŕia), Espana Instituto de Gastroenteroloǵia Boliviano Japon es, Cochabamba, Bolivia Facultad de Medicina, Universidad Mayor de San Simon, Cochabamba, Bolivia Servicio de Medicina Interna, Hospital General Universitario de Alicante, Alicante, Espana Unitat de Medicina Tropical i Salut Internacional Drassanes, Barcelona, Espana

Myocardial involvement in Chagas disease: Insights from cardiac magnetic resonance

BACKGROUNDnChagas disease is becoming a public health problem in Europe because of migratory movements. Cardiac magnetic resonance (CMR) has emerged as a non-invasive tool to assess cardiac tissue characteristics. There is scarce data available on CMR in patients with Chagas disease.nnnOBJECTIVEnTo describe CMR findings in patients with Chagas disease living in a non-endemic area focusing on differentiation from other cardiomyopathies and relation with clinical status.nnnMETHODS AND RESULTSnSixty-seven Chagas disease patients divided into 3 groups-group 1 (indeterminate form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 27), group 2 (ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 19), and group 3 (regional wall motion abnormalities, LV end-diastolic diameter >55 mm or LV ejection fraction <50% on echocardiography; N = 21)--were studied. The presence of wall motion abnormalities and delayed enhancement (DE) by CMR was more frequent in the inferolateral and apical segments. DE distribution in the myocardial wall was heterogeneous (subendocardial 26.8%, midwall 14.0%, subepicardial 22.6%, and transmural 36.0% of total segments with DE) and related to larger cardiac chambers and worse systolic function.nnnCONCLUSIONnPattern of DE in Chagas disease may mimic that of both ischemic and nonischemic cardiomyopathies, with especial predilection for the apical and inferolateral segments of the left ventricle. These findings support that myocardial involvement in chronic Chagas cardiomyopathy (CCC) may be due to both microvascular disturbances and chronic myocarditis and may favor CCC in the differential diagnosis of patients with compatible epidemiological history and heart failure of uncertain etiology.

Short-term follow-up of chagasic patients after benznidazole treatment using multiple serological markers

BackgroundConventional serological tests, using total soluble proteins or a cocktail of recombinant proteins from T. cruzi as antigens, are highly sensitive for Chagas disease diagnosis. This type of tests, however, does not seem to be reliable tools for short- and medium-term monitoring of the evolution of patients after antiparasitic treatment. The aim of the present study was to search for immunological markers that could be altered in the sera from Chagas disease patients after benznidazole treatment, and therefore have a potential predictive diagnostic value.MethodsWe analyzed the reactivity of sera from chagasic patients during different clinical phases of the disease against a series of immunodominant antigens, known as KMP11, PFR2, HSP70 and Tgp63. The reactivity of the sera from 46 adult Chronic Chagas disease patients living in a non-endemic country without vector transmission of T. cruzi (15 patients in the indeterminate stage, 16 in the cardiomiopathy stage and 16 in the digestive stage) and 22 control sera from non-infected subjects was analyzed. We also analyzed the response dynamics of sera from those patients who had been treated with benznidazole.ResultsRegardless of the stage of the sickness, the sera from chagasic patients reacted against KMP11, HSP70, PFR2 and Tgp63 recombinant proteins with statistical significance relative to the reactivity against the same antigens by the sera from healthy donors, patients with autoimmune diseases or patients suffering from tuberculosis, leprosy or malaria. Shortly after benznidazole treatment, a statistically significant decrease in reactivity against KMP11, HSP70 and PFR2 was observed (six or nine month). It was also observed that, following benznidazole treatment, the differential reactivity against these antigens co-relates with the clinical status of the patients.ConclusionsThe recombinant antigens KMP11, PFR2, Tgp63 and HSP70 are recognized by Chagas disease patients sera at any clinical stage of the disease. Shortly after benznidazole treatment, a drop in reactivity against three of these antigens is produced in an antigen-specific manner. Most likely, analysis of the reactivity against these recombinant antigens may be useful for monitoring the effectiveness of benznidazole treatment.

Presentación clínica y complicaciones de malaria importada por Plasmodium falciparum en dos grupos de población: viajeros e inmigrantes

Introduccion La malaria por Plasmodium falciparum es la forma mas agresiva de esta enfermedad, que se registra en el 90% en Africa. Solo adquieren cierto grado de inmunidad los originarios de zonas endemicas. Es incierto si la inmunidad se pierde al perder el contacto con el parasito. Pacientes y metodos Estudio retrospectivo de los pacientes con malaria importada de Africa por P. falciparum en el Hospital Clinic de Barcelona, en el periodo 1999-2005. Comparamos caracteristicas epidemiologicas, clinicas y de laboratorio entre inmigrantes y viajeros. Resultados De 187 pacientes, 85 eran inmigrantes de zona endemica, la mayoria de los cuales residian desde hacia mas de 5 anos en zona no endemica y presentaron menos complicaciones. Discusion Estos datos podrian apuntar a cierta persistencia de la inmunidad cuando personas previamente semiinmunes migran a zonas no endemicas.

Myocardial Deformation Analysis in Chagas Heart Disease With the Use of Speckle Tracking Echocardiography

BACKGROUNDnAssessment of myocardial deformation in Chagas disease may help us to better understand the disease pathophysiology and to detect early myocardial involvement. We aimed to characterize myocardial deformation in patients in different forms of Chagas disease and, specifically, assess differences between patients in the indeterminate form and controls.nnnMETHODS AND RESULTSnSpeckle tracking echocardiography was performed in 98 subjects (22 with Chagas cardiomyopathy, 32 in the indeterminate form, and 44 control subjects) to quantify global and segmental left ventricular (LV) radial strain (RS), circumferential strain (CS), and longitudinal strain (LS). In a subset of patients from the indeterminate and control groups (nxa0= 25), LV peak systolic twist and untwisting velocities were additionally assessed. Global RS, CS, and LS showed a significant decreasing trend across groups. Patients in the indeterminate form had significantly lower global RS and RS in the midinferior segment (median 39.8% vs 49.3% [Pxa0= .046] and 44.0% vs 56.0% [Pxa0= .038], respectively) and lower twist and untwisting velocity (P < .05 for both) compared with control subjects.nnnCONCLUSIONnEvaluation of myocardial deformation, particularly of RS, appears to be a sensitive technique for detection of myocardial involvement in patients in the indeterminate form and provides insights into the still unrevealed pathophysiology of Chagas heart involvement.

Control de la transmisión vertical de Trypanosoma cruzi en España: principal reto de la patología importada

de los principales problemas relacionados con esta enfermedad. Para el diagnostico y tratamiento de las personas afectadas, ha habido en Espana iniciativas diversas originadas desde diversos ambitos. Existen en nuestro pais pruebas diagnosticas fiables para el diagnostico de la infeccion por T. cruzi que han sido debidamente evaluadas10. Tambien se ha hecho un esfuerzo de formacion continuada con la organizacion de talleres de trabajo y en la creacion de documentacion que intenta subrayar los principales problemas del tratamiento de la enfermedad de Chagas, incluyendo los efectos adversos de la medicacion especifica. Al respecto, ya se han publicado dos documentos de consenso avalados por la Sociedad Espanola de Medicina Tropical y Salud Internacional (SEMTSI)11,12. El esfuerzo en la difusion de informacion sobre esta enfermedad debera proseguir y extenderse, en un campo en el que los nuevos conocimientos han cambiado la perspectiva fatalista que se tenia con respecto a las actuaciones que se podian tener frente a esta patologia. Como en todas las especialidades, estar atentos a los nuevos desarrollos permitira poder ofrecer a los afectados las mejores oportunidades para su tratamiento. Las acciones formativas e informativas deberian estar dirigidas no solo a los profesionales de la salud, sino tambien a las personas que padecen la enfermedad. Sin embargo, actualmente el principal reto con relacion a la enfermedad de Chagas en nuestro pais es el cribado en embarazadas y el tratamiento precoz de los recien nacidos afectados. Hay dos hechos que dotan de la mayor relevancia el control de la transmision vertical. Casi la mitad de la poblacion procedente de Latinoamerica que vive en nuestro pais son mujeres en edad fertil. Por otra parte, la eficacia del tratamiento con benznidazol en ninos menores de 1 ano con infeccion por T. cruzi es cercana al 100%, con un buen perfil de tolerancia y seguridad, a diferencia de lo que ocurre en adultos con enfermedad cronica13. Estudios como el efectuado por Paricio et al14, y publicado en este mismo numero de la revista, son importantes para sensibilizar y obligar al Sistema Nacional de Salud a afrontar este importante reto y a dar una respuesta acorde con esta realidad. En este trabajo se muestran los resultados del cribado de la enfermedad de Chagas en mujeres embarazadas de la comunidad valenciana. Los autores encontraron 29 mujeres embarazadas infectadas (4,64%), y aunque no diagnosticaron ningun caso de transmision vertical en esta serie, ya se han detectado y publicado dos casos de Chagas congenito en Espana15,16. En otro estudio efectuado en dos maternidades de Barcelona, la prevalencia de infeccion entre mujeres latinoLa tripanosomiasis americana o enfermedad de Chagas es un importante problema de salud publica en los paises de Latinoamerica. Actualmente, afecta a 8-10 millones de personas1 y se estima que cerca de 100 millones estan expuestas al riesgo de la infeccion. Los flujos migratorios de America Latina han originado cambios sustanciales en la epidemiologia de la enfermedad de Chagas. De ser una enfermedad muy ligada a la pobreza en zonas rurales de America Latina, ha pasado, primero, a las grandes ciudades del continente americano y, posteriormente, a zonas no endemicas. Otros cambios han sido propiciados por los programas de control que se han realizado en los paises afectados, a pesar de que han tenido un desarrollo muy desigual2,3. En general, ha disminuido la tasa de infeccion a traves de la via vectorial. Chile y Uruguay incluso han sido declarados libres de transmision vectorial4,5. El control en los bancos de sangre ha hecho disminuir tambien la transmision a traves de productos sanguineos. En este contexto, la transmision vertical ha cobrado mucha mas relevancia que en el pasado. La inmigracion latinoamericana en Espana alcanzo en el ano 2007 la cifra de 1.594.338 personas, de las cuales alrededor de 700.000 son mujeres en edad fertil6. Tal como muestran algunos estudios, un porcentaje importante de las personas que han llegado de America Latina padece la enfermedad de Chagas en alguna de sus formas (indeterminada, cardiaca, digestiva, etc.)7,8. Por ello, se puede afirmar que la enfermedad de Chagas es una enfermedad emergente en nuestro pais y el impacto en nuestro Sistema Nacional de Salud es y sera importante en el futuro. Los retos que plantea la enfermedad de Chagas en Espana son: el de evitar o controlar las posibles vias de transmision, a saber, la transmision a traves de productos sanguineos o a traves del trasplante de organos y la transmision vertical. El diagnostico, manejo y tratamiento adecuados de las personas con complicaciones de la enfermedad es el otro gran reto de nuestro sistema de salud en relacion con esta patologia. Desde el ano 2005 existe en Espana una normativa que obliga al cribado de todos los donantes de sangre con riesgo de infeccion por Trypanosoma cruzi o a excluirlos de la donacion si el cribado no es posible9. Por ello, si se sigue estrictamente esta normativa, estaria solventado uno