Chagas congénito en atención primaria de la salud en la Provincia de Santa Fe / Congenital Chagas disease in primary health care in Santa Fe province

Actualmente, la transmisión transplacentaria es la vía más frecuente de infección por Trypanosoma cruzi. El diagnóstico y tratamiento temprano de hijos infectados evita el riesgo de desarrollar miocardiopatía y las niñas dejan de ser potenciales fuentes de transmisión congénita. En este estudio se evaluó el seguimiento de hijos de mujeres infectadas por T. cruzi en Centros de Salud de la provincia de Santa Fe. Se estudiaron 19 madres y sus 51 hijos. 45% (23/51) de los hijos no habían sido estudiados previamente, y de éstos 21/23 resultaron negativos mientras que dos niñas de 3 y 7 años estaban infectadas. Los 28 niños restantes ya habían sido estudiados en los Centros de Salud, siendo positivas dos gemelas de 22 meses y una niña de 9 años; los otros 25/28 hijos no estaban infectados. Un 47% (9/19) de las madres tenían como único antecedente la serología materna positiva, y de las 4 mujeres que transmitieron la infección, tres pertenecían a este grupo. La edad promedio de diagnóstico fue: 20±6 años en las madres y 7,4±6,7 años en los hijos. Se requieren estrategias sanitarias que favorezcan el estudio para la infección por T. cruzi en mujeres antes del embarazo y el seguimiento de todos los hijos para no perder la oportunidad de tratamiento

Transplacental transmission is currently the most frequent route of infection by Trypanosoma cruzi. Early diagnosis and treatment of infected children avoids the risk of developing cardiomyopathy, and girls are no longer potential sources of congenital transmission. This study evaluated the follow-up of children of women infected with T. cruzi in Primary Care Centres of the province of Santa Fe. Nineteen mothers and their 51 children were studied. Among the 51 children, 23 had no previous diagnosis (45%). Of these, 21 were negative while 2 girls, ages 3 and 7, were infected. The remaining 28 children already had a diagnosis at the Health Centres, with 2 twins of 22 months and a 9-year-old girl who were positive; the other 25 children were not infected. Among the 19 mothers, 9 (47%) had the positive maternal serology as the only antecedent. Of the 4 women who transmitted the infection, 3 belonged to this group. The average age of diagnosis was: 20 ± 6 years in mothers and 7.4 ± 6.7 years in children. Health strategies are required to promote the detection of infected women before pregnancy and the monitoring of all children so as not to miss the opportunity for treatment

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.

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.

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.

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)

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.