Course of serological tests in treated subjects with chronic Trypanosoma cruzi infection: A systematic review and meta-analysis of individual participant data.

OBJECTIVE: To determine the course of serological tests in subjects with chronic Trypanosoma cruzi infection treated with anti-trypanosomal drugs. METHODS: A systematic review and meta-analysis was conducted using individual participant data. Survival analysis and the Cox proportional hazards regression model with random effects to adjust for covariates were applied. The protocol was registered in the PROSPERO database (http://www.crd.york.ac.uk/PROSPERO; CRD42012002162). RESULTS: A total of 27 studies (1296 subjects) conducted in eight countries were included. The risk of bias was low for all domains in 17 studies (63.0%). Nine hundred and thirteen subjects were assessed (149 seroreversion events, 83.7% censored data) for enzyme-linked immunosorbent assay (ELISA), 670 subjects (134 events, 80.0% censored) for indirect immunofluorescence assay (IIF), and 548 subjects (99 events, 82.0% censored) for indirect hemagglutination assay (IHA). A higher probability of seroreversion was observed within a shorter time span in subjects aged 1-19 years compared to adults. The chance of seroreversion also varied according to the country where the infection might have been acquired. For instance, the pooled adjusted hazard ratio between children/adolescents and adults for the IIF test was 1.54 (95% confidence interval 0.64-3.71) for certain countries of South America (Argentina, Bolivia, Chile, and Paraguay) and 9.37 (95% confidence interval 3.44-25.50) for Brazil. CONCLUSIONS: The disappearance of anti-T. cruzi antibodies was demonstrated along the course of follow-up. An interaction between age at treatment and country setting was found.

Diagnostic reliability of an immunochromatographic test for Chagas disease screening at a primary health care centre in a rural endemic area.

Many patients with Chagas disease live in remote communities that lack both equipment and trained personnel to perform a diagnosis by conventional serology (CS). Thus, reliable tests suitable for use under difficult conditions are required. In this study, we evaluated the ability of personnel with and without laboratory skills to perform immunochromatographic (IC) tests to detect Chagas disease at a primary health care centre (PHCC). We examined whole blood samples from 241 patients and serum samples from 238 patients. Then, we calculated the percentage of overall agreement (POA) between the two groups of operators for the sensitivity (S), specificity (Sp) and positive (PPV) and negative (NPV) predictive values of IC tests compared to CS tests. We also evaluated the level of agreement between ELISAs and indirect haemagglutination (IHA) tests. The readings of the IC test results showed 100% agreement (POA = 1). The IC test on whole blood showed the following values: S = 87.3%; Sp = 98.8%; PPV = 96.9% and NPV = 95.9%. Additionally, the IC test on serum displayed the following results: S = 95.7%; Sp = 100%; PPV = 100% and NPV = 98.2%. Using whole blood, the agreement with ELISA was 96.3% and the agreement with IHA was 94.1%. Using serum, the agreement with ELISA was 97.8% and the agreement with IHA was 96.6%. The IC test performance with serum samples was excellent and demonstrated its usefulness in a PHCC with minimal equipment. If the IC test S value and NPV with whole blood are improved, then this test could also be used in areas lacking laboratories or specialised personnel.

Diagnostic reliability of an immunochromatographic test for Chagas disease screening at a primary health care centre in a rural endemic area

Many patients with Chagas disease live in remote communities that lack both equipment and trained personnel to perform a diagnosis by conventional serology (CS). Thus, reliable tests suitable for use under difficult conditions are required. In this study, we evaluated the ability of personnel with and without laboratory skills to perform immunochromatographic (IC) tests to detect Chagas disease at a primary health care centre (PHCC). We examined whole blood samples from 241 patients and serum samples from 238 patients. Then, we calculated the percentage of overall agreement (POA) between the two groups of operators for the sensitivity (S), specificity (Sp) and positive (PPV) and negative (NPV) predictive values of IC tests compared to CS tests. We also evaluated the level of agreement between ELISAs and indirect haemagglutination (IHA) tests. The readings of the IC test results showed 100% agreement (POA = 1). The IC test on whole blood showed the following values: S = 87.3%; Sp = 98.8%; PPV = 96.9% and NPV = 95.9%. Additionally, the IC test on serum displayed the following results: S = 95.7%; Sp = 100%; PPV = 100% and NPV = 98.2%. Using whole blood, the agreement with ELISA was 96.3% and the agreement with IHA was 94.1%. Using serum, the agreement with ELISA was 97.8% and the agreement with IHA was 96.6%. The IC test performance with serum samples was excellent and demonstrated its usefulness in a PHCC with minimal equipment. If the IC test S value and NPV with whole blood are improved, then this test could also be used in areas lacking laboratories or specialised personnel.

Trypanocide treatment of women infected with Trypanosoma cruzi and its effect on preventing congenital Chagas.

With the control of the vectorial and transfusional routes of infection with Trypanosoma cruzi, congenital transmission has become an important source of new cases. This study evaluated the efficacy of trypanocidal therapy to prevent congenital Chagas disease and compared the clinical and serological evolution between treated and untreated infected mothers. We conducted a multicenter, observational study on a cohort of mothers infected with T. cruzi, with and without trypanocidal treatment before pregnancy. Their children were studied to detect congenital infection. Among 354 "chronically infected mother-biological child" pairs, 132 were treated women and 222 were untreated women. Among the children born to untreated women, we detected 34 infected with T. cruzi (15.3%), whose only antecedent was maternal infection. Among the 132 children of previously treated women, no infection with T. cruzi was found (0.0%) (p<0.05). Among 117 mothers with clinical and serological follow up, 71 had been treated and 46 were untreated. The women were grouped into three groups. Group A: 25 treated before 15 years of age; Group B: 46 treated at 15 or more years of age; Group C: untreated, average age of 29.2 ± 6.2 years at study entry. Follow-up for Groups A, B and C was 16.3 ± 5.8, 17.5 ± 9.2 and 18.6 ± 8.6 years respectively. Negative seroconversion: Group A, 64.0% (16/25); Group B, 32.6% (15/46); Group C, no seronegativity was observed. Clinical electrocardiographic alterations compatible with chagasic cardiomyopathy: Group A 0.0% (0/25); B 2.2% (1/46) and C 15.2% (7/46). The trypanocidal treatment of women with chronic Chagas infection was effective in preventing the congenital transmission of Trypanosoma cruzi to their children; it had also a protective effect on the women's clinical evolution and deparasitation could be demonstrated in many treated women after over 10 years of follow up.

Infección chagásica en niños de cuatro distritos de riesgo de la provincia de Santa Fe / Chagas' infection in children of four districts at risk in Santa Fe province / Infecgáo chagasica em changas de quatro distritos de risco da provincia de Santa Fe

El objetivo del presente estudio fue investigar infección chagásica en niños de 1 a 15 años que residen en zona de riesgo vectorial o con antecedentes migratorios en la provincia de Santa Fe, estimar la/s vía/s más probable/s de infección y comparar la prevalencia con trabajos anteriores. Se realizó un estudio seroepidemiológico en escuelas de los Distritos Garabato, Fortín Olmos y Gato Colorado y la escuela de la comunidad Com Caia del Departamento La Capital. A los seropositivos se les realizó una encuesta para determinar las probables vías de infección. Se comparó la prevalencia actual con la del último control de cada distrito. No se hallaron seropositivos en Com Caia (prevalencia 0%, 0/130). La prevalencia en Garabato fue 1,0% (6/604), Fortín Olmos 1,9% (13/688), Gato Colorado 3,0% (12/399). Disminuyó respecto de los últimos estudios: Garabato 11,2% (año 2000), Fortín Olmos 14,6% (2004), Gato Colorado 6,3% (2006). La vía de infección que se sospecha más frecuente es la congènita, seguida por la vectorial. Se concluye que, a pesar de la disminución de la prevalencia, se deben continuar las acciones de control, principalmente por vías vectorial y congènita.

The aim of the present study was to diagnose Chagas infection in children 1 to 15 years of age living in a risk area or with migrant background in Santa Fe province, to estimate the most probable way of infection and to compare the prevalence with previous works. A seroepidemiological study was conducted in schools in the districts Garabato, Fortin Olmos and Gato Colorado and the community Com Caia in La Capital Department. An inquiry was conducted in positive patients to determine the most probable way of infection. The current prevalence was compared with the last control in each district. No seropositive were found in Com Caia (prevalence 0%, 0/130). In Garabato the prevalence was 1.0% (6/604), Fortin Olmos 1.9% (13/688), Gato Colorado 3.0% (12/399). It decreased in comparison with the latest study: Garabato 11.2% (2000), Fortin Olmos 14.6% (2004), Gato Colorado 6.3% (2006). The most suspected way of infection was congenital, followed by vector one. We conclude that, although the prevalence decreased, it must be continued mainly vector and congenital controls actions.

O objetivo deste estudo foi investigar a infecgáo chagásica em criangas de 1 a 15 anos que moram em zona de risco vetorial ou com antecedentes de migragáo na provincia de Santa Fe, estimar a/as via/s mais provável/veis de infecgáo e comparar prevalencia com trabalhos anteriores. Foi realizado um estudo soroepidemiológico em escolas nos distritos Garabato, Fortin Olmos e Gato Colorado e na escola da comunidade Com Caia no departamento La Capital. Os soropositivos foram entrevistados para determinar as prováveis vias da infecgáo. A prevalencia atual foi comparada com a do último controle em cada distrito. Náo foram encontrados soropositivos em Com Caia (prevalencia 0%, 0/130). A prevalencia em Garabato foi 1,0% (6/604), Fortin Olmos 1,9% (13/688), Gato Colorado 3,0% (12/399). Diminuiu a respeito dos últimos estudos: Garabato 11,2% (ano 2000), Fortin Olmos 14,6% (2004), Gato Colorado 6,3% (2006). A via de infecgáo que se suspeita como sendo a mais frequente é a congenita, seguida pela vetorial. Concluise que, apesar da diminuigáo da prevalencia, devem continuar sendo realizadas agoes de controle, principalmente por vias vetorial e congenita.

Infección chagásica en niños de cuatro distritos de riesgo de la provincia de Santa Fe / Chagas infection in children of four districts at risk in Santa Fe province / Infecgáo chagasica em changas de quatro distritos de risco da provincia de Santa Fe

El objetivo del presente estudio fue investigar infección chagásica en niños de 1 a 15 años que residen en zona de riesgo vectorial o con antecedentes migratorios en la provincia de Santa Fe, estimar la/s vía/s más probable/s de infección y comparar la prevalencia con trabajos anteriores. Se realizó un estudio seroepidemiológico en escuelas de los Distritos Garabato, Fortín Olmos y Gato Colorado y la escuela de la comunidad Com Caia del Departamento La Capital. A los seropositivos se les realizó una encuesta para determinar las probables vías de infección. Se comparó la prevalencia actual con la del último control de cada distrito. No se hallaron seropositivos en Com Caia (prevalencia 0%, 0/130). La prevalencia en Garabato fue 1,0% (6/604), Fortín Olmos 1,9% (13/688), Gato Colorado 3,0% (12/399). Disminuyó respecto de los últimos estudios: Garabato 11,2% (año 2000), Fortín Olmos 14,6% (2004), Gato Colorado 6,3% (2006). La vía de infección que se sospecha más frecuente es la congÞnita, seguida por la vectorial. Se concluye que, a pesar de la disminución de la prevalencia, se deben continuar las acciones de control, principalmente por vías vectorial y congÞnita.(AU)

The aim of the present study was to diagnose Chagas infection in children 1 to 15 years of age living in a risk area or with migrant background in Santa Fe province, to estimate the most probable way of infection and to compare the prevalence with previous works. A seroepidemiological study was conducted in schools in the districts Garabato, Fortin Olmos and Gato Colorado and the community Com Caia in La Capital Department. An inquiry was conducted in positive patients to determine the most probable way of infection. The current prevalence was compared with the last control in each district. No seropositive were found in Com Caia (prevalence 0%, 0/130). In Garabato the prevalence was 1.0% (6/604), Fortin Olmos 1.9% (13/688), Gato Colorado 3.0% (12/399). It decreased in comparison with the latest study: Garabato 11.2% (2000), Fortin Olmos 14.6% (2004), Gato Colorado 6.3% (2006). The most suspected way of infection was congenital, followed by vector one. We conclude that, although the prevalence decreased, it must be continued mainly vector and congenital controls actions.(AU)

O objetivo deste estudo foi investigar a infecgáo chagásica em criangas de 1 a 15 anos que moram em zona de risco vetorial ou com antecedentes de migragáo na provincia de Santa Fe, estimar a/as via/s mais provável/veis de infecgáo e comparar prevalencia com trabalhos anteriores. Foi realizado um estudo soroepidemiológico em escolas nos distritos Garabato, Fortin Olmos e Gato Colorado e na escola da comunidade Com Caia no departamento La Capital. Os soropositivos foram entrevistados para determinar as prováveis vias da infecgáo. A prevalencia atual foi comparada com a do último controle em cada distrito. Náo foram encontrados soropositivos em Com Caia (prevalencia 0%, 0/130). A prevalencia em Garabato foi 1,0% (6/604), Fortin Olmos 1,9% (13/688), Gato Colorado 3,0% (12/399). Diminuiu a respeito dos últimos estudos: Garabato 11,2% (ano 2000), Fortin Olmos 14,6% (2004), Gato Colorado 6,3% (2006). A via de infecgáo que se suspeita como sendo a mais frequente é a congenita, seguida pela vetorial. Concluise que, apesar da diminuigáo da prevalencia, devem continuar sendo realizadas agoes de controle, principalmente por vias vetorial e congenita.(AU)

Perspectiva interdisciplinaria para el abordaje de una enfermedad infecciosa: chagas o tripanosomiasis americana / Interdisciplinary perspective to approach an infectious disease: american trypanosomiasis or chagas disease

La enfermedad de Chagas, producida por elTrypanosomacruziy transmitida por un insecto triatomino, es de grancomplejidad. En el control de esta endemia no puedeconsiderarse la enfermedad como un hecho individualy sólo biológico. Entre sus múltiples componentes debeconsiderarse la relación de los sujetos con el hábitat, losmodos de producción, las condiciones culturales, lasrelaciones sociales y las formas organizativas.Como profesionales del campo de la salud intentamosnuevos enfoques que integran diferentes miradas disciplinaresy modos de intervención distintos, donde “el otro” recuperesu ser sujeto y no esté convocado a desempeñar un merorol de paciente. Posiciones que implican favorecer procesosparticipativos, escuchar a los propios protagonistas (mujerescon Chagas, equipos de salud, referentes comunitarios)recuperar sus peculiares visiones, poner en palabras lo nodicho sobre esta enfermedad silenciosa y silenciada, y develarlo que el Chagas esconde. Constituye una herramientaimportante a la hora de pensar propuestas de trabajo.

Chagas disease, caused by Trypanosoma cruzi and transmitted by a triatomine insectis extremely complicated. When controlling this endemic disease, the disease cannot beconsidered as an individual and merely biological fact. Among its many components therelationship of individuals to the habitat, production modes, cultural conditions, socialrelationships and organizational forms must be considered.As health professionals we present new approaches that integrate different disciplinesand modes of intervention, where “the other” recovers his/her individual being and isnot merely called upon to play a role as a patient. Positions that encourage participativeprocesses involving listening to the protagonists themselves (women with Chagas, healthteams, community references), recovering their unique visions, communicating what isnot said about this silent and hushed up disease, and revealing what Chagas hides areimportant tools when thinking about work proposals.

Perspectiva interdisciplinaria para el abordaje de una enfermedad infecciosa: chagas o tripanosomiasis americana / Interdisciplinary perspective to approach an infectious disease: american trypanosomiasis or chagas disease

La enfermedad de Chagas, producida por elTrypanosomacruziy transmitida por un insecto triatomino, es de grancomplejidad. En el control de esta endemia no puedeconsiderarse la enfermedad como un hecho individualy sólo biológico. Entre sus múltiples componentes debeconsiderarse la relación de los sujetos con el hábitat, losmodos de producción, las condiciones culturales, lasrelaciones sociales y las formas organizativas.Como profesionales del campo de la salud intentamosnuevos enfoques que integran diferentes miradas disciplinaresy modos de intervención distintos, donde ôel otroö recuperesu ser sujeto y no esté convocado a desempeñar un merorol de paciente. Posiciones que implican favorecer procesosparticipativos, escuchar a los propios protagonistas (mujerescon Chagas, equipos de salud, referentes comunitarios)recuperar sus peculiares visiones, poner en palabras lo nodicho sobre esta enfermedad silenciosa y silenciada, y develarlo que el Chagas esconde. Constituye una herramientaimportante a la hora de pensar propuestas de trabajo.(AU)

Chagas disease, caused by Trypanosoma cruzi and transmitted by a triatomine insectis extremely complicated. When controlling this endemic disease, the disease cannot beconsidered as an individual and merely biological fact. Among its many components therelationship of individuals to the habitat, production modes, cultural conditions, socialrelationships and organizational forms must be considered.As health professionals we present new approaches that integrate different disciplinesand modes of intervention, where ôthe otherö recovers his/her individual being and isnot merely called upon to play a role as a patient. Positions that encourage participativeprocesses involving listening to the protagonists themselves (women with Chagas, healthteams, community references), recovering their unique visions, communicating what isnot said about this silent and hushed up disease, and revealing what Chagas hides areimportant tools when thinking about work proposals.(AU)

Humoral immune response against P2ß from Trypanosoma cruzi in persons with chronic Chagas disease: its relationship with treatment against parasites and myocardial damage.

We investigated the relationship between potentially pathogenic antibodies against a Trypanosoma cruzi ribosomal protein (P2ß) and the evolution of Chagas disease and the effect of trypanocidal treatment on these variables. Seventy-eight patients with chronic Chagas disease who were followed-up for more than 20 years were divided into three groups: 30 asymptomatic persons undergoing specific treatment (group A), 37 asymptomatic persons not undergoing specific treatment (group B), and 11 patients with chronic chagasic cardiomyopathy (CCC) who were not treated. Five patients in group B showed evolution to myocardial abnormalities. Among persons with CCC, six showed no changes; the remaining persons showed progression of cardiac involvement. Levels of antibodies to P2ß in persons in group A decreased from their initial values. This finding was not observed in persons in groups B and C. Comparisons at the end of the follow-up showed lower amounts of antibodies to P2ß in groups A and C. These findings support the benefits of specific treatment during chronic infection.

Utilidad de la técnica de aglutinación directa en el diagnóstico de la infección chagásica / Usefulness of the direct agglutination test for the diagnosis of chagasic infection

La técnica de aglutinación directa para diagnóstico de infección chagásica es sencilla y económica. Tiene buena sensibilidad y especificidad cuando es utilizada junto con otras técnicas serológicas y/o parasitológicas. Ha sido reemplazada por otras reacciones de mayor rapidez en los resultadosy más fácil lectura (ELISA, hemaglutinación indirecta). Actualmente es difícil conseguir equipos comerciales. Se presentan en el siguiente trabajo una serie de casos que muestran la utilidad de la aglutinación directa para determinar precozmente infección aguda y/o congénita y para diferenciarinfecciones agudas de crónicas.

The direct agglutination technique for chagasic infection diagnosis is easy to perform and inexpensive. It has good sensitivity and specificity when used in conjunction with other serological and/or parasitological techniques. It has been replaced with other reactions with faster results and easiness to read (i.e. immunoenzymatic assay (ELISA) and indirect hemagglutination). Currently it is difficult to obtaincommercial kits. In the present paper we present a series of cases that show the usefulness of the direct agglutination test to early determine acute and/or congenital infection and to differentiate acute from chronic infections.

Confirman la utilidad de la quimioterapia específica en la enfermedad de Chagas crónica / Confirmation of the usefulness of chemotherapy in the treatment of chronic Chagas disease

La evaluación del tratamiento tripanocida en adultos con enfermedad de Chagas crónica requiere estudios de seguimiento muy prolongados. Ciento doce adultos con infección crónica por T. cruzi, asintomáticos, residentes en la Ciudad de Santa Fe fueron evaluados durante 23 años en promedio mediante estudios parasitológicos, serológicos y clínicos. De ellos, 55 fueron tratados (27 con nifurtimox y 28 con benznidazol) y 57 permanecieron sin tratar. Se demostró la eficacia del tratamiento específico en el 45.5% de los pacientes tratados, por su negativización parasitológica y serológica convencional persistente, acompañada de un efecto preventivo en la evolución del daño miocárdico. En este grupo tratado, otro 23.6% de los infectados presentaron serología dudosa o seroconversión negativa completa en el último control. Estos probablemente se incorporen en los próximos años al grupo de pacientes curados. En los infectados que no recibieron tratamiento específico se observó que la serología convencional permaneció siempre positiva y que las alteraciones electrocardiográficas compatibles con miocardiopatía chagásica crónica fueron 5 veces mayores que la que presentó el grupo de pacientes tratados.

Confirman la utilidad de la quimioterapia específica en la enfermedad de Chagas crónica / Confirmation of the usefulness of chemotherapy in the treatment of chronic Chagas disease

La evaluación del tratamiento tripanocida en adultos con enfermedad de Chagas crónica requiere estudios de seguimiento muy prolongados. Ciento doce adultos con infección crónica por T. cruzi, asintomáticos, residentes en la Ciudad de Santa Fe fueron evaluados durante 23 años en promedio mediante estudios parasitológicos, serológicos y clínicos. De ellos, 55 fueron tratados (27 con nifurtimox y 28 con benznidazol) y 57 permanecieron sin tratar. Se demostró la eficacia del tratamiento específico en el 45.5% de los pacientes tratados, por su negativización parasitológica y serológica convencional persistente, acompañada de un efecto preventivo en la evolución del daño miocárdico. En este grupo tratado, otro 23.6% de los infectados presentaron serología dudosa o seroconversión negativa completa en el último control. Estos probablemente se incorporen en los próximos años al grupo de pacientes curados. En los infectados que no recibieron tratamiento específico se observó que la serología convencional permaneció siempre positiva y que las alteraciones electrocardiográficas compatibles con miocardiopatía chagásica crónica fueron 5 veces mayores que la que presentó el grupo de pacientes tratados.(AU)

Infección chagásica y antecedentes epidemiológicos relacionados, en un área de baja endemicidad de Argentina / No disponible

Fundamento: La Enfermedad de Chagas afecta principalmente a poblaciones rurales tropicales y subtropicales de América. Su distribución se ha modificado por migraciones, emergiendo como un problema de salud urbano. El Departamento La Capital (Santa Fe, Argentina) es considerado de baja endemicidad para esta enfermedad. El objetivo del presente estudio fue caracterizar epidemiológicamente esta infección en una comunidad suburbana de La Capital. Métodos: Estudio descriptivo, de corte transversal. Lugar: Ángel Gallardo, Departamento La Capital, Santa Fe, Argentina. Periodo 2006-2007.Muestra: En mayores de 14 años: selección aleatoria de la muestra, n=72; en menores de 14años: totalidad de la población escolar previo consentimiento, n=116.Resultados: Seropositividad: 0,8% en <14 años, 29,2% en >14 años. Disminuyó con el nivel de instrucción. Resultaron infectados: 45,4% de los trabajadores rurales; 46,2% de los inmigrantes de Bolivia, Norte de Argentina y/o Norte de Santa Fe; 42,9% sabían que estaban infectados. Conclusiones: La prevalencia es muy superior a la estimada para la región. Aún en áreas sin riesgo entomológico, se debe buscar activamente la infección en comunidades con características epidemiológicas particulares. Muchos desconocen que están infectados y no se realizan los controles pertinentes. Se deben mantener los programas de control, para evitar el reinicio de ciclo vectorial en la región (AU)

Background: Chagas disease mainly affects tropical and subtropical rural populations of America. Its distribution has been modified by migrations, becoming a urban health problem.La Capital department in Santa Fe, Argentina, is considered a low endemicity area for this disease. The aim of the study was to characterize this infection in an epidemiological way in a suburban community of La Capital. Methods: Descriptive and cross- section study. Location: Ángel Gallardo, La Capital department, Santa Fe, Argentina. Period 2006-2007.Sample: Over 14 yo.: random selection, n=72; below 14 yo.: the whole school population with previous agreement, n=116.Results: Positive: 0,8% in <14 yo., 29,2% in >14 yo. Decrease with the school level. Infected:45,4% of rural workers; 46,2% of immigrants from Bolivia, North of Argentina and/or North of Santa Fe; 42,9% know they were infected. Conclusions: The prevalence is much superior to the one estimated for the region. Even in areas without entomological risk, the searching of the infection should be actively taken in communities with particular epidemiological characteristics. Many people do not know they are infected and they do not do the appropiate controls. The control programs should be kept in order to prevent the starting over of the vectorial cicle in the region (AU)

Evaluación de ELISA F29 como marcador de eficacia del tratamiento etiológico en la enfermedad de Chagas / Assessment of ELISA F29 as a marker of etiological treatment efficacy for Chagas disease

A transversal study was performed on sera from chronic chagas ic patients treated with nifurtimox (Nx) or benznidazole (Bz), in order to evaluate the Trypanosoma cruzi flagellar calcium-binding protein (F29) as a marker for therapeutic effectiveness. An ELISA was used with these F29 recombinant antigen, and its relation to conventional serology (CS) and parasitological and clinical evolution was analysed. Sera from 118 patients with retrospective, serological, parasitological and clinical information was available, were analyzed. Patients were grouped into: A) 30 treated patients whose CS became negative after treatment; B) 34 treated patients whose CS remained positive; C) 54 untreated patients. A double-blind trial was conducted simultaneously in all serum samples, by means ofCS (indirect hemagglutination, direct agglutination and indirect immunofluorescence) and ELISA F29. The ELISA F29 test was non reactive in: 100 percent of group A, 82.4 percent of group B and 13 percent> of group C. The infected patients who presented electrocardiographic alterations compatible with chronic chagasic myocardiopathy (n = 11) were reactive for ELISA F29. All patients whose parasitological studies (xenodiagnosis and/or strout method) were positive presented a high reactivity to the ELISA F29 test. The correlation between ELISA F29 and CS was statistically significant (p < 005) in the treated group whose CS was non reactive (group A) and the untreated group (group C). As opposed to this, in the group of treated patients whose CS remained positive (group B), the ELISA F29 test was reactive only in a 17.6 percent>. These results suggest that the fast and user-friendly ELISA F29 test could be useful to monitor changes after trypanocidal treatment.

La proteína flagelar F29 es una proteína ligadora de calcio del Trypanosoma cruzi. En el presente trabajo se realizó un estudio transversal en sueros de pacientes con infección crónica por T. cruzi tratados con nifurtimox (Nx) o benznidazol (Bz) y no tratados, para evaluar el antígeno F29 como marcador de eficacia terapéutica. Se utilizó un ensayo inmuno-enzimático con la proteína recombinante F29 (ELISA F29) y se analizó su relación con la serología convencional (SC) y la evolución parasitológica y clínica en esos pacientes. Se estudiaron 118 sueros de pacientes que formaban parte de una cohorte, de los cuales se disponía de información retrospectiva, serológica, parasitológica y clínica. Los pacientes se dividieron en 3 grupos: A) 30 tratados negativizaron SC post-tratamiento; B) 34 tratados permanecieron con SC reactiva; C) 54 no tratados. Las muestras de suero se procesaron a doble ciego en forma simultánea mediante serología convencional (hemoaglutinación indirecta, aglutinación directa e inmunofluorescencia indirecta) y ELISA F29. El test ELISA F29 resultó no reactivo en: 100 por ciento del grupo A, 82,4 por ciento del grupo B y 13 por ciento del grupo C. Los infectados con alteraciones electrocardiográficas compatibles con miocardiopatía chagásica crónica (n = 11) fueron reactivos al ELISA F29. Los pacientes en quienes los estudios parasitológicos (xenodiagnóstico y/o strout) fueron (+) presentaron elevada reactividad al ELISA F29. La correlación entre ELISA F29 y SC en los pacientes tratados con SC no reactiva (grupo A) y no tratados (grupo C), fue significativa (p < 0,05). En cambio, en pacientes tratados que mantuvieron la SC reactiva (grupo B) el test de ELISA F29 fue reactivo sólo en 17,6 por ciento. Estos resultados sugieren que el test ELISA F29, rápido y sencillo, podría ser útil para monitorear cambios post-tratamiento tripanocida.

Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe city (Argentina), over a mean follow-up of 21 years: parasitological, serological and clinical evolution.

The efficacy of treatment with nifurtimox and/or benznidazole among adults with chronic Chagas disease with no previous electrocardiographic disturbances was evaluated over a mean follow-up of 21 years, by means of conventional serology, xenodiagnosis, clinical examination, electrocardiograms and chest X-ray. One hundred and eleven patients, between 17 and 46 years old, were studied: 54 underwent treatment (nifurtimox 27, benznidazole 27) and 57 remained untreated (control group). Xenodiagnosis was performed on 65% of them: 36/38 of the treated and 9/34 of the untreated patients had previous positive xenodiagnosis. Post-treatment, 133 xenodiagnoses were performed on 41 patients, all resulting negative. In the control group, 29 xenodiagnoses were performed on 14 patients; 2 resulted positive. Sera stored during the follow-up were simultaneously analyzed through conventional serology tests (IHA; DA-2ME; IIF). The serological evolution in the treated group was: a) 37% underwent negative seroconversion (nifurtimox 11, benznidazole 9); b) 27.8% decreased titers (nifurtimox 9, benznidazole 6), 9 showed inconclusive final serology (nifurtimox 7, benznidazole 2); c) 35.2% remained positive with constant titers (nifurtimox 7; benznidazole 12). The control group conserved the initial antibody levels during the follow-up. In the clinical evolution, 2/54 (3.7%) of the treated and 9/57 (15.8%) of the untreated patients showed electrocardiographic disturbances attributable to Chagas myocardiopathy, with a statistically relevant difference (p<0.05). Treatment caused deparasitation in at least 37% of the chronically infected adults and a protective effect on their clinical evolution.

Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe city (Argentina), over a mean follow-up of 21 years: parasitological, serological and clinical evolution

The efficacy of treatment with nifurtimox and/or benznidazole among adults with chronic Chagas disease with no previous electrocardiographic disturbances was evaluated over a mean follow-up of 21 years, by means of conventional serology, xenodiagnosis, clinical examination, electrocardiograms and chest X-ray. One hundred and eleven patients, between 17 and 46 years old, were studied: 54 underwent treatment (nifurtimox 27, benznidazole 27) and 57 remained untreated (control group). Xenodiagnosis was performed on 65 percent of them: 36/38 of the treated and 9/34 of the untreated patients had previous positive xenodiagnosis. Post-treatment, 133 xenodiagnoses were performed on 41 patients, all resulting negative. In the control group, 29 xenodiagnoses were performed on 14 patients; 2 resulted positive. Sera stored during the follow-up were simultaneously analyzed through conventional serology tests (IHA; DA-2ME; IIF). The serological evolution in the treated group was: a) 37 percent underwent negative seroconversion (nifurtimox 11, benznidazole 9); b) 27.8 percent decreased titers (nifurtimox 9, benznidazole 6), 9 showed inconclusive final serology (nifurtimox 7, benznidazole 2); c) 35.2 percent remained positive with constant titers (nifurtimox 7; benznidazole 12). The control group conserved the initial antibody levels during the follow-up. In the clinical evolution, 2/54 (3.7 percent) of the treated and 9/57 (15.8 percent) of the untreated patients showed electrocardiographic disturbances attributable to Chagas myocardiopathy, with a statistically relevant difference (p<0.05). Treatment caused deparasitation in at least 37 percent of the chronically infected adults and a protective effect on their clinical evolution.

Avaliamos a eficácia do nifurtimox e/ou benznidazol, durante 21 anos em média, em adultos chagásicos crônicos sem alterações eletrocardiográficas iniciais, mediante sorologia convencional, xenodiagnóstico, exames clínicos, eletrocardiográficos e radiografia do tórax. Estudamos 111 pacientes (17 a 46 anos): 54 foram tratados (27 com nifurtimox e 27 com benznidazol) e 57 formaram o grupo controle. Foram submetidos ao xenodiagnóstico 65 por cento dos pacientes estudados: 36/38 tratados e 9/34 do grupo controle com xenodiagnóstico positivo prévio. Após tratamento, foram realizados 133 xenodiagnósticos em 41 pacientes, sendo todos negativos. Foram realizados 29 xenodiagnósticos em 14 pacientes do grupo controle, 2 foram positivos. A sorologia convencional foi realizada em soros estocados durante o seguimento. Evolução sorológica. Grupo tratado: a) 37 por cento negativaram (nifurtimox 11, benznidazol 9); b) 27,8 por cento diminuíram a titulação (nifurtimox 9, benznidazol 6), 9 deles apresentaram sorologia final discordante (nifurtimox 7, benznidazol 2; c) 35,2 por cento permaneceram positivos com titulação constante (nifurtimox 7, benznidazol 12). Grupo controle: conservou os níveis iniciais de anticorpos durante o seguimento. Evolução clínica: 2/54 (3,7 por cento) pacientes tratados e 9/57 não tratados apresentaram alterações eletrocardiográficas atribuíveis a miocardiopatia chagásica. Diferenças estatisticamente significantes (p<0,05). O tratamento produziu efeito de combate ao parasita em pelo menos 37 por cento dos infetados crônicos adultos e efeito protetor na evolução clínica.

Estudo longitudinal e quimioterapia específica em crianças, com doença de Chagas crônica, residentes em área de baixa endemicidade da República Argentina / Longitudinal study and specific chemotherapy in children with chronic Chagas' disease, residing in a low endemicity area of Argentina

Apresenta-se a avaliação clinicoepidemiológica de 95 crianças chagásicas crônicas em idades entre 1 e 14 anos moradoras de Santa Fé, Argentina, não tratadas e tratadas com nifurtimox ou benznidazol, com acompanhamento de até 24 anos. Todas tinham vários antecedentes de risco para transmissão do Trypanosoma cruzi: vetorial, congênito e/ou transfusão sangüínea. O diagnóstico da infecção foi feito através de sorologia convencional. O exame clínico foi complementado por eletrocardiograma, radiografias de tórax e, análise de sangue e urina para avaliação das funções hepáticas. No pós-tratamento, utilizaram-se técnicas idênticas às do diagnóstico, sendo que 33 crianças tiveram, também, avaliação parasitológica. Dentre 24 crianças não tratadas, 14 foram controlados por 8 a 24 anos e mantiveram sorologia positiva e o estado clínico inicial. Das 71 crianças tratadas, 49 tiveram acompanhamento de 4 a 24 anos: 14 mantiveram anticorpos anti-Trypanosoma cruzi; 6 resultados discordantes e 29 negativaram a sorologia. Destas, 9 apresentaram oscilações sorológicas, antes da negativação definitiva. A mediana do tempo de negativação pós-tratamento foi, respectivamente, de 3,5 e 8 anos para crianças de 1 a 6 e 7 a 14 anos. A percentagem de soronegativos diminuiu com a idade em que se medicou, desde 75 por cento em <4 anos até 43 por cento em > 9 anos. A intolerância ao tratamento foi de 3,8 por cento. Nenhuma criança modificou seu estado clínico nesta observação.

[Longitudinal study and specific chemotherapy in children with chronic Chagas' disease, residing in a low endemicity area of Argentina]. / Estudo longitudinal e quimioterapia específica em crianças, com doença de Chagas crônica, residentes em área de baixa endemicidade da República Argentina.

Clinical and epidemiological results of 95 treated and untreated chronic chagasic children, with an up to 24 years follow-up period are presented. This population studied in the 1/14 age bracket, residing in Santa Fe city, Argentina, was diagnosed through Chagas-specific conventional serologic reactions. Clinical examination was supplemented with electrocardiogram, chest X-rays, and blood and urine tests for evaluating hepatic function. The drugs employed were nifurtimox or benznidazole. In post treatment period xenodiagnosis was made in 33 patients. Regarding Trypanosoma cruzi transmission, the studied individuals presented multi-risk antecedents: vectorial, congenital and/or blood transfusion. Among 24 untreated children 14 were controlled during 8/24 years: all this patients maintained the initial antibody concentration and clinical status. From 71 treated patients 49 were followed-up 4/24 years: 14 remained positive, 6 presented dubious results, and 29 showed final non-reactive results. 9 of this presented sometimes oscilating results. In 1/6 age bracket children, the serology turned negative after 3.5 years (median) once the treatment was finished, while patients treated in the 7/14 age bracket, the median of negativization was 8 years. 3.8% did not tolerate the drug. None of the groups changed their clinical condition. The untreated children did not change the serology. The percentage of treated children presenting negative serological results decrease according to the age when treatment was given: 75% became negative when treated at < or =4 years old and 43% when treated at > or =9 years old.

Evolutive behavior towards cardiomyopathy of treated (nifurtimox or benznidazole) and untreated chronic chagasic patients

The aim of this work was to compare the evolution of chronic chagasic untreated patients (UTPs) with that of benznidazole or nifurtimox-treated patients (TPs). A longitudinal study from a low endemic area (Santa Fe city, Argentina) was performed during an average period of 14 years. Serological and parasitological analyses with clinical exams, ECG and X-chest ray were carried out. At the onset, 19/198 infected patients showed chagasic cardiomyopathy (CrChM) while 179 were asymptomatic. In this latter group the frequency of CrChM during the follow-up was lower in TPs compared with UTPs (3.2 per cent vs 7 per cent). Within the CrChM group, 2/5 TPs showed aggravated myopathy whereas this happened in 9/14 UTPs. Comparing the clinical evolution of all patients, 5.9 per cent of TPs and 13 per cent of UTPs had unfavourable evolution, but the difference is not statistically relevant. Serological titers were assessed by IIF. Titers equal to or lower than 1/64 were obtained in 86 per cent of the TPs, but only in 38 per cent of UTPs. The differences were statistically significant (geometric mean: 49.36 vs. 98.2). Antiparasitic assessment of the drugs (xenodiagnosis) proved to be effective. The low sensitivity in chronic chagasic patients must be born in mind. Despite treated patients showed a better clinical evolution and lower antibody levels than untreated ones, it is necessary to carry on doing research in order to improve therapeutic guidelines, according to the risk/benefit equation and based on scientific and ethical principles.

Chagas congénito en la ciudad de Santa Fé. Diagnóstico y tratamiento / Congenital Chagas disease in the city of Santa Fé. Diagnosis and treatment

We studied 6123 pregnant women and their 341 newborn (NB), from Santa Fe city, by the following serological tests for chagasic infection: Direct Agglutination with and without 2-mercaptoethanol, Indirect Hemagglutination and Indirect Immunofluorescence test, and by identification of parasites by Fresh drops, Strout and/or by Xenodiagnosis. The prevalence of seropositivity found in pregnant women was of 14.62 with a 73 of migratory history. The parasitological studies yielded 9/341 incidence of transplacentary infection. Clinical examinations were made in the infected newborn (NB). They were treated with Benznidazol or Nifurtimox, and post-treatment evolution was evaluated. We registered connatal infection in twin-brothers. Brothers/sisters (siblings) of infected NB were also studied. Some of them were seropositive and the others seronegative. Results here obtained show that this way of transmission is important, and should be considered even in low endemicity areas. The parasitological assays proved to be decisive for the NB infection diagnosis (Table 1). The serological assays enabled us to follow the non-infected NB up to their negativization. A 6 month follow-up is recommended. It is impossible to define only one clinical outline because both symptomatic and asymptomatic infected NB may be found with gestational age at term and pre-term and when born with a weight above or below 2000 g. We obtained parasitological and serological negativization in all cases. The chagasic pregnant woman does not necessarily transmit the infection to all her descendents. Only 2.64 are infected. It is possible to systematize the diagnosis without extra resources beyond the usual ones.