Cribado y transmisión congénita de la enfermedad de Chagas en población usuaria del Hospital Dr. Félix Bulnes Cerda y Atención Primaria de Salud del Servicio de Salud Metropolitano Occidente de Santiago, Chile / Screening and congenital transmission of Chagas Disease in the user population of the Dr. Félix Bulnes Cerda Hospital and Primary Health Care Services of the Metropolitan Health Service West of Santiago, Chile

Resumen Introducción: El año 2016, el Hospital Dr. Félix Bulnes Cerda (HDFBC) implementó el tamizaje obligatorio de anticuerpos anti Trypanosoma cruzi, para pesquisar nuevos casos de la enfermedad de Chagas (ECH) en mujeres embarazadas y recién nacidos (RN) y brindar tratamiento antiparasitario oportuno. Ello, porque la transmisión transplacentaria de T. cruzi continúa siendo un importante problema de salud pública. Objetivo: Presentar la información epidemiológica generada luego de la implementación del cribado de la ECH en el HDFBC del SSMOCC, al cabo de dos años de iniciada su operación. Material y Métodos: Cribado por inmunoquimioluminiscencia (IQLU), confirmación por IFI, ELISA y/o western blot. Seguimiento de RN: mediante RPC, IFI, ELISA e IQLU. Resultados: Entre abril de 2016 y julio de 2018 se analizó un total de 14.012 muestras de pacientes; 62 resultaron reactivas (0,53% seropositividad) y 28 fueron confirmadas positivas (prevalencia de 0,2%). Del total, 11.780 fueron de mujeres gestantes (n: 41 casos reactivos y 10 confirmadas con ECH), con prevalencia de 0,085%. Los restantes 18 casos positivos fueron usuarios no gestantes, con sospecha clínica de ECH y casos de estudios familiares, mostrando una prevalencia de 0,81%. El seguimiento a 10 RN y lactantes hijos de madres chagásicas descartó la transmisión transplacentaria Completaron tratamiento con nifurtimox 30% de las madres. Discusión: La implementación del programa en el HDFBC cumple los objetivos de cribado, pesquisa y diagnóstico de la ECH así como el seguimiento y tratamiento oportuno del RN. La prevalencia de 0,085% de la ECH en la población gestante como la de 0,2% en población total son significativamente menores (p-valor < 0,01) que la prevalencia de 0,7% reportada (año 2016) para la Región Metropolitana (RM); sugerimos que es consecuencia de la implementación del programa nacional y local. La transmisión congénita de 0% es acorde a la tasa de [0,91 x 10.000] reportada el 2017 para la RM. En base al aprendizaje adquirido, durante el desarrollo de la investigación, se entrega sugerencias para aportar al funcionamiento del programa.

Abstract Background: In 2016, the Hospital Dr. Félix Bulnes Cerda (HDFBC) implemented the mandatory screening of anti Trypanosoma cruzi antibodies in pregnant women, thus complying with national regulations to detect new Chagas disease cases (CHD) in mother and child, whose early detection mediates timely pharmacological treatment. This, because the congenital transmission continues the main active transmission mechanisms of T. cruzi and a major public health problem for the country. Aim: To present the epidemiological information generated after the implementation of the ECH screening in the SSFCC HFBC, two years after its operation began. Methods: Screening test: inmunequimioluminiscence (IQLU), certification by IFI, ELISA and/or western blot. Follow up of newborn infants with PCR, IFI, ELISA and IQLU. Results: Between April 2016 and July 2018, 14.012 subject's samples were examined of which 62 resulted reactive (0.53% seropositivity) in the total studied population where 28 patients resulted positive for CHD, which corresponds to a 0.2% prevalence. Of the total population, 11.780 were pregnant women, of these 41 were reactive and 10 were confirmed with CHD thus showing a prevalence of 0.085%. The other 18 positive cases of non-pregnant patients corresponded a prevalence of 0.81%. Also, 10 newborn and infant children of mothers with CHD were followed up. In all, congenital transmission (0%) was ruled out. Nifurtimox treatment of the mothers were completed in 30% of them. It is concluded that the implementation of the program in the HDFBC fulfills the objectives of screening, detection and diagnosis of CHD, so as the timely follow-up and pharmacologic treatment of the newborn. The 0.085% prevalence of CHD in pregnant women as the 0.20% in total population are significantly lower (p-valor < 0.01) than the 0.7% reported in 2016 for the Metropolitan Region (MR), a fact that we suggest is a consequence of the national program implementation. Likewise, the 0% transplacental transmission is accorded to the rate of 0.91 x 10.000 live births reported in 2017 for the MR. Based on the learning acquired during the development of the research, recommendations are given to contribute to the operation of the program.

Maternal risk factors for the transmission of congenital chagas disease

The present article looks at the association between the epidemiological history of women infected with Trypanosoma cruzi and the risk of vertical transmission. Eighty-three chronically infected mothers and their 237 children were studied, using a cohort design. All patients reside in Santa Fe city, Argentina. Twenty-five women transmitted the infection to 38 children. The potential risk factors evaluated in the mothers were exposure to vector transmission, blood transfusion history, maternal seropositivity, parasitemia and age at birth of the child. 72% (18/25) of the mothers who transmitted the infection to their children, had little or no contact with the vector, while only 28% (7/25) of the mothers presented a history of medium or high risk of vector infection. The differences were significant (p < 0.05). Forty-one percent of the women who presented maternal history as the probable route of infection, transmitted the parasite to more than one child (1.86 ± 0.33; CI95% = 1.03-2.68). In addition, the most frequent history, among the women who transmitted the disease to their children, was the absence of exposure to vector transmission and transfusion with unknown maternal serology. The route of infection was probably transplacental. These observations suggest that there are family genetic characteristics involved in vertical transmission. The parasite was found in 71% of the mothers who transmitted the infection to their children and were able to perform xenodiagnoses. After controlling for the other variables, the logistic regression analysis showed that xenodiagnosis (+) is a risk factor for congenital transmission; the relative risk was 12.2 (95% confidence interval: 2.9 - 50.1). No differences were found when analyzing the mother's age and transfusion history. The highest risk of congenital transmission was associated with detectable parasitemia and less maternal exposure to the vector.

Urban Chagas disease in children and women in primary care centres in Buenos Aires, Argentina

The primary objective of this study was to estimate the prevalence of this disease in women of childbearing age and children treated at health centres in underserviced areas of the city of Buenos Aires. Demographic and Chagas disease status data were collected. Samples for Chagas disease serology were obtained on filter paper and the reactive results were confirmed with conventional samples. A total of 1,786 subjects were screened and 73 positive screening results were obtained: 17 were from children and 56 were from women. The Trypanosoma cruziinfection risk was greater in those individuals who had relatives with Chagas disease, who remember seeing kissing bugs, who were of Bolivian nationality or were born in the Argentine province of Santiago del Estero. The overall prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is currently predominantly urban. The observed prevalence requires health programme activities that are aimed at urban children and their mothers. Most children were infected congenitally, which reinforces the need for Chagas disease screening of all pregnant women and their babies in Argentina. The active search for new cases is important because the appropriate treatment in children has a high cure rate.

Prevention of congenital Chagas through treatment of girls and women of childbearing age

It is currently unknown whether treatment of Chagas disease decreases the risk of congenital transmission from previously treated mothers to their infants. In a cohort of women with Chagas disease previously treated with benznidazole, no congenital transmission of the disease was observed in their newborns. This finding provides support for the treatment of Chagas disease as early as possible.

Congenital transmission of Trypanosoma cruzi in central Brazil. A study of 1,211 individuals born to infected mothers

Transmission of Trypanosoma cruzi during pregnancy is estimated to occur in less than 20% of infected mothers; however, the etiopathogenesis is not completely understood. The Centre for Studies on Chagas Disease provides confirmation of T. cruzi infection for individuals living in central Brazil. In this retrospective hospital-based study, all requests for diagnosis of T. cruzi infection in individuals less than 21 years old from 1994-2014 were searched. We end with 1,211 individuals and their respective infected mothers. Congenital transmission of infection was confirmed in 24 individuals (2%) in central Brazil, an area where the main T. cruzi lineage circulating in humans is TcII. This low prevalence of congenital Chagas disease is discussed in relation to recent findings in the south region of Brazil, where TcV is the main lineage and congenital transmission has a higher prevalence (approximately 5%), similar to frequencies reported in Argentina, Paraguay and Bolivia. This is the first report to show geographical differences in the rates of congenital transmission of T. cruzi and the relationship between the prevalence of congenital transmission and the type of Tc prevalent in each region.

Immune Responses and Vaccine Development for Cytomegalovirus Infections.

Aims: (1) To review the published literature on immune biology of host- Cytomegavovirus (CMV) interactions and to discuss the host immune responses against viral infection, providing insights into the complex interplay between the host and the virus that facilitates viral persistence. (2) To report on the status of CMV vaccines that are currently in preclinical and clinical development, outlining important questions about the nature of protective immune responses that will be required of potential CMV immunization strategies. Methodology: A Pub Med search of original articles and reviews in English language only between the years 1974-2013 was conducted using “CMV infection”, “CMV vaccines”, “CMV immune responses” and “CMV clinical trials” as keywords. Inclusion criteria were a description of the CMV disease in immune compromised patients and in individuals affected by the virus through congenital transmission, clinical observations in the course of CMV infection, the overview of the host immune responses and CMV factors in the outcome of CMV infection, the current status of therapeutic strategies and vaccine development. Results: CMV is found throughout the world in all geographic and socioeconomic groups, but, in general, it is more widespread in developing countries and in areas of lower socioeconomic conditions. CMV still remains a major human pathogen causing significant morbidity and mortality in immune suppressed or immune compromised individuals. Between 50% and 80% of adults in the United States are infected with CMV by 40 years of age. CMV is the most common congenitally transmitted virus, resulting in approximately 1 in 150 children born with congenital CMV infection, and in about 1 in 750 children developing permanent disabilities due to CMV. Thus, development of vaccines against CMV infections has been a major biomedical research priority. Conclusion: There is a need for an effective CMV vaccine that will protect immune compromised transplant patients as well as newborns, although the key requirements for protection of these two populations (and the optimal vaccine strategy to provide this protection) may differ. To date, only the Towne vaccine – a live, attenuated CMV vaccine – has undergone efficacy evaluation. Application of molecular biological techniques, coupled with an improved understanding of the CMV genome, should allow design of safer, more immunogenic, live, attenuated vaccines.

Estudio seroepidemiológico para estimar el riesgo de infección congénita por toxoplasma gondii en Guayaquil, Ecuador / Serological and epidemiological screening to estimate congenital toxoplasma gondii infection in Guayaquil, Ecuador

Exámenes serológicos, por Hemaglutinación indirecta (HAI) y Elisa para anticuerpos anti Toxoplasma gondii se practicaron a niños y adolescentes, distribuidos en 4 grupos: 0 < 5 .años, 5 < 10, 10 < 15 y de 15 < 20, para obtener los datos de prevalencia e incidencia quinquenal, así como, por entrevista para identificar factores de riesgo; los datos se analizaron estadísticamente, como variables independientes y correlaciones bivariadas. Se examinaron 578: 285 varones y 292 mujeres, (1 no consignado), promedio de edad 9,7 años. La prevalencia encontrada es 60,2 con descenso de 18 porciento respecto a 1989. Se discuten hipótesis para explicar esta disminución. La incidencia aumenta rápido hasta los 10 años. No se estableció ninguna correlación con los factores de riesgo incluidos, excepto en el contacto con gatos menores de 6 meses (gatitos). El riesgo de transmisión congénita se estima en 18 por diez mil; en consecuencia se esperarían 106 casos anuales, con 69 asintomáticos (65 porciento), y 37 (35 porciento) con síntomas: 17 con daños leves, 11 con graves y 9 mortinatos. Los 28 niños con lesiones manifiestas, más un número no determinado con lesiones tardías de los 69 asintomáticos incorporan una población que causa un impacto económico y social aún no establecido...

Serological testing, by indirect haemagglutination and ELISA was performed in 4 age groups: 0 to <5, 5 to <10, 10 to <15 and 15 to <20 years old, to find prevalence and quinquennial incidence. An interview to assess risk factors was performed. The statistical analysis was performed for independent variables and bivariate correlations to calculate the odds ratio. The total number of observations was 578: 285 male and 292 female (1 not determined) and median age was 9.7. An increase in the prevalence was related to age, reaching 60.2 percent in the group between 15 and 20 years old, when compared to the same age group in 1989 (78.3 percent) showing an 18 percent decrease. Several hypotheses to explain this decrease were proposed. There is a steep increase at the age of 10. The statistical analysis does not demonstrate a direct correlation with any of the risk factors consigned in the interview, with the exception of exposure to young felines (kittens). The risk for acquiring congenital toxoplasmosis was estimated as 1.8 per thousand (18 per ten thousand), hence 106 cases are expected per year, with 69 (65 percent) of them being asymptomatic, and 37 with different degrees of severity: 17 with mild, 11 severe and 9 with death at birth. Each year there would be 28 newborns with evident lesions and additionally an undetermined number of cases with late onset lesions within the initially asymptomatic group (65 percent), with unknown socioeconomic impact...

Prevalência de anticorpos IgG anti-toxoplasmose em alunos de curso superior / Prevalence of IgG anti-toxoplasmosis antibodies in students in college

Objetivo: verificar a prevalência de anticorpos IgG em alunos de uma faculdade. Métodos: foram realizados testessorológicos em 200 alunos, homens e mulheres, com média de 24 anos, no período de dezembro de 2011 a março de2012, utilizando a técnica de hemaglutinação indireta. Resultados: a freqüência de soropositividade nos alunos estudadosfoi de 24,5%, esses resultados estão de acordo com dados encontrados no Brasil de 20 a 83% de soropositividade paratoxoplasmose. Conclusão: os resultados obtidos neste estudo mostram que há baixa frequência de toxoplasmose napopulação estudada, porém, reafirmam a importância de testes sorológicos para a prevenção da toxoplasmose congênita,uma vez que a toxoplasmose na mulher é de grande importância em saúde pública, podendo acarretar danos irreversíveisao feto e até a morte, devido à passagem do protozoário via transplacentária

Introduction: toxoplasmosis is a zoonosis that affects millions of people around the world, when acquired duringpregnancy can be transmitted to the fetus. It can cause irreversible damages or even death. Objective: thus, the presentstudy aimed to determine the incidence of IgG antibodies in students of College. Methods: serological testing wasconducted on 200 students about of 24 years age, in the period from december 2011 to march 2012. The technique ofindirect hemaglutination was used. Results: the frequency of seropositivity in the students was 24,5%. Conclusion:these results are consistent with data found in Brazil from 20 to 83% seropositivity for toxoplasmosis. Results show thatthere is a low frequency of toxoplasmosis in the population studied, however, reaffirm the importance of serologicaltests for the prevention of congenital toxoplasmosis. Because toxoplamosis is an important public health problem, it isdangerous for pregnant women and fetus.

Congenitally transmitted visceral leishmaniasis: report of two brazilian human cases

Visceral leishmaniasis is a relevant public health problem worldwide. Most of the reported cases in Latin America are from Brazil. Herein we report two human cases of congenitally transmitted visceral leishmaniasis in two patients who developed symptoms during pregnancy. The diagnosis was made by visual examination of Leishmania parasites in bone marrow aspirates of the mothers and by detecting parasite kDNA in bone marrow samples of the newborn children using polymerase chain reaction.

O inquérito nacional de soroprevalência de avaliação do controle da doença de Chagas no Brasil (2001-2008) / The national survey of seroprevalence for evaluation of the control of Chagas disease in Brazil (2001-2008)

Um inquérito de soroprevalência de doença de Chagas foi realizado em amostra representativa da população com idade até cinco anos de toda a área rural brasileira, exceto o Estado do Rio de Janeiro. Foram estudadas 104.954 crianças, que tiveram amostras de sangue coletadas em papel de filtro e submetidas a testes de screening pelas técnicas de imunofluorescência indireta (IFI) e ELISA em um único laboratório. Todas as amostras com resultados positivos ou indeterminados, juntamente com 10 por cento daquelas com resultados negativos, foram enviadas para um laboratório de referência e aí submetidas a novos testes por IFI e ELISA, além de western blot TESA (Trypomastigote Excreted Secreted Antigen). Para as crianças com resultado final positivo foi agendada uma re-visita para coleta de sangue venoso do próprio participante e das suas mães e familiares. Da avaliação do conjunto de testes resultaram 104 (0,1 por cento) resultados positivos, dos quais apenas 32 (0,03 por cento) foram confirmadas como infectadas. Destas, 20 (0,02 por cento) com positividade materna concomitante (sugerindo transmissão congênita), 11 (0,01 por cento) com positividade apenas na criança (indicativo de provável transmissão vetorial), e uma criança positiva cuja mãe havia falecido. Em 41 situações ocorreu confirmação apenas nas mães, sugerindo transferência passiva de anticorpos maternos; em 18 a positividade não se confirmou nem nas crianças nem nas suas mães; e em 13 não foi possível a localização de ambas. As 11 crianças que adquiriram a infecção por provável via vetorial distribuíram-se predominantemente na região nordeste (Piauí, Ceará, Rio Grande do Norte, Paraíba e Alagoas), acrescidas de um caso no Amazonas e um no Paraná. Dos 20 casos com provável transmissão congênita sobressaiu-se o Rio Grande do Sul, com 60 por cento deles, representando este o primeiro relato de diferenças regionais na transmissão congênita da doença de Chagas no Brasil, possivelmente relacionada à existência de Trypanosoma cruzi grupo IId e IIe, atualmente classificados como TcV e TcVI. Os resultados deste inquérito apontam para a virtual inexistência de transmissão de doença de Chagas por via vetorial no Brasil em anos recentes, resultante da combinação dos programas regulares e sistemáticos de combate á moléstia e de mudanças de natureza socioeconômica observadas no país ao longo das últimas décadas. Por outro lado, reforçam a necessidade de manutenção de um programa de controle que garanta a consolidação deste grande avanço.

A survey for seroprevalence of Chagas disease was held in a representative sample of Brazilian individuals up to 5 years of age in all the rural areas of Brazil, with the single exception of Rio de Janeiro State. Blood on filter paper was collected from 104,954 children and screened in a single laboratory with two serological tests: indirect immunofluorescence and enzyme linked immunoassay. All samples with positive or indetermined results, as well as 10 percent of all the negative samples were submitted to a quality control reference laboratory, which performed both tests a second time, as well as the western blot assay of TESA (Trypomastigote Excreted Secreted Antigen). All children with confirmed final positive result (n = 104, prevalence = 0.1 percent) had a follow-up visit and were submitted to a second blood collection, this time a whole blood sample. In addition, blood samples from the respective mothers and familiar members were collected. The infection was confirmed in only 32 (0.03 percent) of those children. From them, 20 (0.025 percent) had maternal positive results, suggesting congenital transmission; 11 (0.01 percent) had non-infected mothers, indicating a possible vectorial transmission; and in one whose mother had died the transmission mechanism could not be elucidated. In further 41 visited children the infection was confirmed only in their mothers, suggesting passive transference of maternal antibodies; in other 18, both child and mother were negative; and in 13 cases both were not localized. The 11 children that acquired the infection presumably through the vector were distributed mainly in the Northeast region of Brazil (States of Piauí, Ceará, Rio Grande do Norte, Paraíba and Alagoas), in addition to one case in Amazonas (North region) and another in Parana (South region). Remarkably, 60 percent of the 20 cases of probably congenital transmission were from a single State, Rio Grande do Sul, with the remaining cases distributed in other states. This is the first report demonstrating regional geographical differences in the vertical transmission of Chagas disease in Brazil, which probably reflects the predominant Trypanosoma cruzi group IId and IIe (now TcV and TcVI) found in this state. Overall, these results show that the regular and systematic control programs against the transmission of Chagas disease, together with socioeconomic changes observed in Brazil in the last decades, interrupted the vectorial transmission in Brazil, resumed in the few cases found in this national survey. Furthermore they reinforce the need for maintenance of control programs for the consolidation of this major advance in public health.

Transmisión congénita de Trypanosoma cruzi en crías de ratas Wistar con infección chagásica aguda / Congenital Trypanosoma cruzi transmission in pups of Wistar rats with acute Chagas infection

Se evaluó la transmisión congénita de Trypanosoma cruzi en crías de ratas Wistar con infección aguda. Las ratas fueron inyectadas intraperitonealmente con 1,5x10(4) tripomastigotes metacíclicos de la cepa I/PAN/VE/00/PLANALTO linaje TcI. La parasitemia fue significativamente mayor (P<0,05) en las ratas infectadas preñadas (IP) que en las ratas infectadas vírgenes (IV). Las crías de las ratas IP a los 15, 30, 45 y 60 días de nacidas (dn) no mostraron tripanosomas circulantes. El ensayo ELISA reveló aumento progresivo de IgM anti-T. cruzi en el suero de 6 crías (24%) de las ratas IP entre los 15 y 60 dn. La IgG anti-T. cruzi disminuyó progresivamente en las crías de ratas IP y fueron negativos a los 60 dn. Cortes de corazón y músculo esquelético del 15% de las crías con 60 dn de las ratas IP mostraron antígeno de T. cruzi con PAP. ADN de T. cruzi fue detectado por PCR en el suero de 4 crías (16%) a los 60 dn de ratas IP. La presencia de anticuerpos IgM anti- T. cruzi y ADN del parásito en las crías de ratas con infección aguda, pueden ser considerados como un criterio de infección congénita en las crías sin parasitemia patente.

Congenital Trypanosoma cruzi transmission was evaluated in pups of Wistar rats with acute Chagas infection. The rats were injected intraperitoneally with 1.5 x 10(4) metacyclic tripomastigotes from the I/PAN/VE/00/PLANALTO strain TcI lineage. Parasitemia was significantly higher (P<0.05) in the pregnant infected rats (PI) than in the infected virgin rats (VI). The offspring of the PI rats at 15, 30, 45 and 60 days after birth (ab) did not show circulating trypanosomes. An ELISA test revealed progressive increase of anti-T. cruzi IgM in the serum of pups (24%) of the PI rats between 15 and 60 days. Anti-T. cruzi IgM decreased progressively in the PI pups and became negative at 60 ab. Heart and skeletal muscle sections of 15% of the pups of the PI rats at 60 ab showed T. cruzi antigen with PAP. T. cruzi DNA was detected through PRC in the serum of 4 pups (16%) of PI rats at 60 ab. Presence of anti-T. cruzi IgM and parasite DNA in the pups of rats with acute infection can be considered as a criterion of congenital infection in pups without evident parasitemia.

Transmisión congénita de Trypanosoma cruzi en ratas Wistar de segunda generación / Congenital transmission of Trypanosoma cruzi in second generation Wistar rats

Se presentan los resultados de un estudio experimental sobre la transmisión congénita de Trypanosoma cruzi en crías de ratas albinas (Rattus norvegicus), cepa Wistar de segunda generación. El curso de la infección chagásica fue evaluado en las ratas infectadas inicialmente (RII) inyectadas con las formas metacíclicas del parásito, en las crías de la primera (C1ªG) y segunda generación (C2ªG), mediante pruebas de diagnóstico seroparasitológicas y molecular (PCR). En las RII se demostró infección aguda caracterizada por parasitemias patentes entre los 12 y 45 días post-inoculación (pi), e incremento en la respuesta inmune humoral con títulos desde 1:64 y 1:2048; en la fase crónica se evidencio ausencia de parasitemias y mantenimiento de una moderada respuesta humoral en el 100% de las madres. Las C1ªG no presentaron tripomastigotes en la sangre circulante, la prueba de IFI, reveló seropositividad apreciable en el 75% de los sueros. En las C2ªG, los exámenes directos de sangre y el hemocultivo, resultaron negativos; los xenodiagnósticos mostraron un 18,2% de positividad. Las pruebas serológicas empleadas (IFI y ELISA) detectaron un 31,8% y 34,1% anticuerpos circulantes anti-T. cruzi. La PCR aplicada a los sueros, presentó un bajo porcentaje de muestras positivas (6,8%) y en los tejidos (corazón y músculo esquelético) se observó una alta positividad de 54,5% y 45,4%, respectivamente. La presencia de formas flageladas en la sangre, la persistencia de la serología positiva por anticuerpos humorales transferidos vía materna y la permanencia de restos de ADN de T. cruzi en sueros y tejidos en un número importante de crías, confirma la infección congénita a su progenie, en segunda generación. Estos resultados son de gran importancia para una mejor comprensión de la epidemiología de la enfermedad de Chagas congénita

The results of the experimental study concerning the congenital transmission of Trypanosoma cruzi in second generation strain Wistar albino rats are presented. The course of the Chagas infection was evaluated in rats initially infected with the metacyclic forms of the parasite (RII) in first (C1stG) and second (C2ndG) generation offspring using parasitological, serological and molecular (PCR) diagnostic tests. In the RII, an acute infection characterized by patent parasitemias between 12 and 45 days post-inoculation and an increase in the humoral immune response with titers of 1:64 and 1:2048 in the chronic phase demonstrated the absence of parasitemia and maintenance of a moderate humoral response in 100% of the mothers. The C1stG did not show tripomastigotes in the blood circulation and the IIF test showed considerable seropositive in 75% of the sera. In C2ndG, direct blood and hemoculture exams performed were negative, while 18.2% of the xenodiagnosis were positive. The serological tests used (IIF and ELISA) detected 31.8% and 34.1% anti-T. cruzi circulating antibodies. The PCR applied to the serum presented a low percentage of positive (6.8%) samples and in tissues (heart and skeletal muscle) high positives of 54.5% and 45.4% respectively were observed. The presence of flagellated forms in the blood, the persistence of serological positive for humoral antibodies transferred by the mother and the permanence of remaining DNA of the T. cruzi in serum and tissues in a significant number of offspring confirm the congenital infection to their offspring in the second generation. These results are of great importance for the better understanding of the epidemiology of Chagas disease

Transmisión congénita por Trypanosoma cruzi: aspectos de la respuesta inmune fetal / Congenital transmission of Trypanosoma cruzi: Aspects of the fetal immune response

La respuesta inmune mediada por células en neonatos y fetos de madres infectadas por Trypanosoma cruzi ha sido objeto de estudio en modelos murinos, existiendo datos que apoyan la idea de que el sistema inmune fetal puede ser competente. Esta revisión sintetiza los resultados obtenidos en estudios multidisciplinarios sobre casos de enfermedad de Chagas congénito, los cuales señalan que dicha afección depende del equilibrio entre complejos fenómenos, tales como la respuesta inmune adaptativa en la madre de tipo Th2 asociada a altas parasitemias, la invasión de la placenta y el cordón umbilical por los parásitos y la respuesta inmune específica en el feto caracterizada por una activación de células T CD8+ productoras de IFN-γ capaces de limitar la multiplicación del parásito, así como la morbi mortalidad y los linajes de mayor virulencia del parásito que pudieran atravesar con facilidad la placenta y llegar a ser más patógenos para el feto/neonato

The cell-mediated immune response in infants and fetuses of mothers infected with Trypanosoma cruzi has been studied in mouse models and there are data supporting the idea that the fetal immune system may be competent. This review synthesizes the results obtained from multidisciplinary studies of cases of congenital Chagas disease, which indicate that this condition depends on the equilibrium between complex phenomena, such as a maternal type Th2 adaptative immune response associated with high parasitemia, the invasion of placental and umbilical cord by parasites and a fetal specific immune response characterized by an activation of CD8 T cells producing IFN-gamma able to limit parasite multiplication and morbidity/mortality; and that in lineages of higher virulence the parasite could easily cross the placenta and be more pathogenic to the fetus/neonate

Transmisión congénita de la enfermedad de Chagas en el Paraguay / Congenital transmission of Chagas disease in Paraguay

Las estrategias actuales recomendadas para el diagnostico de la infección congénita chagásica requieren del diagnóstico serológico convencional en mujeres embarazadas para detectar su infección y la confirmación parasitológica en recién nacidos infectados verticalmente. La detección de parásitos en sangre no resulta un método fácil de aplicar a gran escala y a nivel de salud pública por lo que se recomienda finalmente la serología convencional, es decir la detección de IgG anti-T. cruzi en infantes mayores a 8 meses de edad. Teniendo en cuenta estas recomendaciones nuestro grupo ha diseñado estrategias operativas en áreas rurales endémicas que permiten la rápida detección y tratamiento de infantes infectados congénitamente. Demostramos que la descentralización de los estudios serológicos de los grandes Hospitales Regionales ayuda a la rápida identificación de las mujeres infectadas, como también el registro de su estado de infección en las fichas familiares, prenatal y pediátrica. Los resultados de más de 15 años de estudio de nuestro grupo, indican que a pesar de la alta sensibilidad de la técnica reacción en cadena de la polimerasa (PCR), resulta muy complejo su empleo con fines de diagnóstico a nivel rural y en gran escala, siendo muy útil para evaluar el tratamiento realizado en los niños infectados. La serología convencional permite la detección inequívoca de anticuerpos del tipo IgG en infantes infectados congénitamente después de los 8 meses de edad (tiempo máximo observado para el clearence de anticuerpos maternos). Sin embargo esta estrategia hace que el tiempo requerido en el seguimiento para descartar transmisión congénita disminuya la adherencia durante el periodo de seguimiento con una importante pérdida de niños que no son traídos al control. La detección de casos de transmisión congénita aumenta notablemente cuando se utiliza una combinación de las técnicas serológicas convencionales y un ELISA que hemos diseñado con el antígeno recombinante de fase aguda, “shed acute phase antigen” (SAPA) que permite la detección inequívoca de infantes infectados congénitamente a los 3 meses de edad

The current strategies recommended for the diagnosis of congenital Chagas disease require the conventional serological diagnosis in pregnant women to detect their infection and the parasitological confirmation in the congenitally infected newborns. The detection of parasites in blood is not a method easy to apply at large scale and at public health level. Therefore, the conventional serology is recommended, i.e. detection of anti-T.cruzi IgG in infants older than eight months of age. Considering these recommendations, our group has designed operative strategies in endemic rural areas that allow the rapid detection and treatment of congenitally infected infants. We have demonstrated that the decentralization of the serological studies from the Regional Hospitals contributes to the fast identification of the infected women together with the registration of their infection status in the family, prenatal and pediatric files. The results of over fifteen years of study of our group indicate that, in spite of the high sensitivity of PCR, its use with diagnosis purposes is very complex at large scale and in rural areas. However, the polymerase chain reaction (PCR) technique is very useful to evaluate the treatment of infected children. The conventional IgG serology allows the unequivocal detection of congenitally infected infants after eight months of age (maximum time observed for the clearance of maternal antibodies). However, this strategy makes that the time required to rule out a congenital transmission in the follow-up diminishes adherence with an important loss of children that are not brought to control. The detection of congenital transmission cases increases remarkably when a combination of the conventional serological techniques and an ELISA that we designed with the recombinant protein “shed acute phase antigen” (SAPA) is used, allowing the unequivocal detection of congenitally infected children at three months of age

Etiological treatment of young women infected with Trypanosoma cruzi, and prevention of congenital transmission / Tratamento etiológico de mulheres jovens infectadas com Trypanosoma cruzi e prevenção da transmissão congênita

The objective was to detect Trypanosoma cruzi infection in 32 children in Salta, Argentina, born to 16 chronically infected young women who were treated with benznidazole. Tests were performed to assess the efficacy of treatment after 14 years. At the end of the follow up, 87.5 percent of the women were non-reactive to EIA tests, 62.5 percent to IHA and 43.8 percent to IFA. 62.5 percent of the women were non-reactive according to two or three serological tests. No infected children were detected among the newborns of mothers treated before their pregnancy.

O objetivo foi detectar a infecção do Trypanosoma cruzi em 32 crianças nacidas de 16 jovens mulheres cronicamente infectadas e tratadas com benzinadol, em Salta, Argentina. Testes foram feitos para avaliar a eficácia após 14 anos do tratamento. Ao final do seguimento 87.5 por cento das mulheres foram não reativas ao EIA, 62.5 por cento ao IHA e 43.8 por cento ao IFA. 62.5 por cento das mulheres foram não reativas de acordo a 3 ou 2 testes serológicos. Nenhuma criança infectada foi detectada entre os recém-nascidos de mães tratadas antes da gravidez.

Transmisión vectorial y congénita del Trypanosoma cruzi en Las Lomitas, Formosa / Vectorial and congenital transmission of Trypanosoma cruzi in Las Lomitas, Formosa

La enfermedad de Chagas causada por el Trypanosoma cruzi es una causa importante de morbimortalidad en Latino América. El objetivo de este estudio fue describir las tasas de infestación en las viviendas de cuatro comunidades aborígenes de Las Lomitas (Región del Gran Chaco), Formosa, Argentina; la tasa de infección en la población infantil residente en las mismas, en donantes de sangre y en mujeres embarazadas que asistieron al Hospital de Las Lomitas y la tasa de infección congénita de niños nacidos de mujeres infectadas durante el período de estudio. La tasa de infestación en 172 viviendas evaluadas en 2006 alcanzó el 32%. La prevalencia de infección en 445 personas fue de 17.5% y en menores de 5 años de edad fue 8.6%. La tasa de infección en donantes de sangre alcanzó a 18.6% y en mujeres embarazadas fue 29.1%. La tasa de infección considerada congénita en 47 niños nacidos de mujeres infectadas residentes en viviendas bajo vigilancia fue de 17.0%. El estudio mostró, al momento de su inicio, índices compatibles con transmisión vectorial activa. Después del control vectorial con insecticidas, la tasa de infestación se redujo a 3.3%. El sistema de salud local incorporó procedimientos de prevención primaria y secundaria para evitar nuevos casos e instaurar el tratamiento de la población infectada.

Chagas disease, caused by Trypanosoma cruzi, is a major cause of morbidity and mortality in Latin America. The objective of this study was to describe the rate of infestation in four aboriginal communities in Las Lomitas (Great Chaco Region), Formosa, Argentina; the rate of infection in children residing in these communities, in blood donors and in pregnant women who received care at the Hospital Las Lomitas, as well as the rate of congenital infection in children born to women infected during the study period. The rate of infestation of 172 households evaluated in 2006 reached 32%. Prevalence of infection among 445 people was 17.5% and in children under 5 years old it was 8.6%. The rate of infection reached 18.6% in blood donors and 29.1% in pregnant women. The rate of infection among 47 children born to infected women, and living in residences under vectorial surveillance was 17.0%. These infections were considered as congenital. This study showed indexes compatible with active vectorial transmission at the beginning. After vectorial control with insecticides the infestation rate has been reduced to 3.3%. The local health system has introduced high impact procedures of primary and secondary prevention in order to prevent new cases and to treat infected people.

Elimination of Chagas disease transmission: perspectives

One hundred years after its discovery by Carlos Chagas, American trypanosomiasis, or Chagas disease, remains an epidemiologic challenge. Neither a vaccine nor an ideal specific treatment is available for most chronic cases. Therefore, the current strategy for countering Chagas disease consists of preventive actions against the vector and transfusion-transmitted disease. Here, the present challenges, including congenital and oral transmission of Trypanosoma cruzi infections, as well as the future potential for Chagas disease elimination are discussed in light of the current epidemiological picture. Finally, a list of challenging open questions is presented about Chagas disease control, patient management, programme planning and priority definitions faced by researchers and politicians.

Freqüência de anticorpos anti-Neospora caninum em vacas e fetos provenientes de municípios do sul de Minas Gerais / Frequency of anti-Neospora caninum antibodies in cows and fetuses from Municipalities of Southern Minas Gerais

The objective of this study was to determine the frequency of antibodies anti-Neospora caninum in cows and fetuses from Municipalities of southern Minas Gerais. A total of 559 serum samples of cows of the a bank of sera formed from of serum samples collected at 18 dairy farms, distributed for seven Municipalities of the Lavras Micro region, southern Minas Gerais, and 575 serum samples of cows and 503 serum samples of fetuses were collected at slaughter house of Campo Belo, MG. Serum samples were submitted to the indirect fluorescent antibody tests (IFAT), using as antigen taquizoites of N. caninum, and as cut-off values the serum dilution of 1:25 for the fetuses serum and 1:200 for the cows. The frequency in the cows of the Lavras Micro region was of 91.2 percent (510/559). The frequency was of 97.2 percent (559/575) and 12.7 percent (64/503) for females and fetuses from slaughter house, respectively. These results indicate that the infection by N. caninum is endemic in dairy cattle of the Lavras Micro region, southern Minas Gerais, Brazil.

O objetivo deste estudo foi determinar a freqüência de anticorpos anti-Neospora caninum em vacas e fetos provenientes de municípios do sul de Minas Gerais. Foram utilizadas 559 amostras de soros de vacas de um banco de soros formado a partir de amostras coletadas em 18 propriedades produtoras de leite, distribuídas por sete municípios da microrregião de Lavras, MG; e 575 amostras de soros de vacas e 503 de soros fetais, ambas coletadas no matadouro de Campo Belo, MG. As amostras foram submetidas à reação de imunofluorescência indireta (RIFI-IgG), para pesquisa de anticorpos anti-N. caninum, considerando como ponto de corte o título de 1:200 para as fêmeas bovinas e 1:25 para os soros fetais. A freqüência média global de anticorpos anti-N. caninum em vacas leiteiras das fazendas da microrregião de Lavras foi de 91,2 por cento (510/559) e nas vacas abatidas em matadouro e fetos de 97,2 por cento (559/575) e 12,7 por cento (64/503), respectivamente. Esses resultados indicam que a infecção por N. caninum está amplamente distribuída em rebanhos leiteiros da microrregião de Lavras, sul de Minas Gerais.

Transmisión congénita de la enfermedad de Chagas en el Paraguay / Congenital transmission of Chagas disease in Paraguay

Las estrategias actuales recomendadas para el diagnostico de la infección congénita chagásica requieren del diagnóstico serológico convencional en mujeres embarazadas para detectar su infección y la confirmación parasitológica en recién nacidos infectados verticalmente. La detección de parásitos en sangre no resulta un método fácil de aplicar a gran escala y a nivel de salud pública por lo que se recomienda finalmente la serología convencional, es decir la detección de IgG anti-T. cruzi en infantes mayores a 8 meses de edad. Demostramos que la descentralización de los estudios serológicos de los grandes Hospitales Regionales ayuda a la rápida identificación de las mujeres infectadas, como también el registro de su estado de infección en las fichas familiares, prenatal y pediátrica. Los resultados de más de 15 años de estudio de nuestro grupo, indican que a pesar de la alta sensibilidad de la técnica reacción en cadena de la polimerasa (PCR), resulta muy complejo su empleo con fines de diagnóstico a nivel rural y en gran escala, siendo muy útil para evaluar el tratamiento realizado en los niños infectados. La serología convencional permite la detección inequívoca de anticuerpos deltipo IgG en infantes infectados congénitamente después de los 8 meses de edad (tiempo máximo observado para el clearence de anticuerpos maternos). Sin embargo esta estrategia hace que el tiempo requerido en el seguimiento para descartar transmisión congénita disminuya la adherencia durante el periodo de seguimiento con una importante pérdida de niños que no son traídos al control. La detección de casos de transmisión congénita aumenta notablemente cuando se utiliza una combinación de las técnicas serológicas convencionales y un ELISA que hemos diseñado con el antígeno recombinante de fase aguda, “shed acute phase antigen” (SAPA) que permite la detección inequívocade infantes infectados congénitamente a los 3 meses de edad.

The current strategies recommended for the diagnosis of congenital Chagas disease require the conventional serological diagnosis in pregnant women to detect their infectionand the parasitological confirmation in the congenitally infected newborns. The detection of parasites in blood is not a method easy to apply at large scale and at public health level. Therefore, the conventional serology is recommended, i.e. detection of anti-T.cruzi IgG in infants older than eight months of age. Considering these recommendations, ourgroup has designed operative strategies in endemic rural areas that allow the rapid detection and treatment of congenitally infected infants. We have demonstrated that the decentralization of the serological studies from the Regional Hospitals contributes to thefast identification of the infected women together with the registration of their infection status in the family, prenatal and pediatric files. The results of over fifteen years of study of our group indicate that, in spite of the high sensitivity of PCR, its use with diagnosis purposes is very complex at large scale and in rural areas. However, the polymerase chain reaction (PCR) technique is very useful to evaluate the treatment of infected children The conventional IgG serology allows the unequivocal detection of congenitally infected infants after eight months of age (maximum time observed for the clearance of maternal antibodies). However, this strategy makes that the time required to rule out a congenital transmission in the follow-up diminishes adherence with an important loss of children that are not brought to control. The detection of congenital transmission casesincreases remarkably when a combination of the conventional serological techniques and an ELISA that we designed with the recombinant protein “shed acute phase antigen”(SAPA) is used, allowing the unequivocal detection of congenitally infected children at three months of age.

Toxoplasma gondii infection in pregnancy

Toxoplasmosis is caused by an intracellular protozoan, Toxoplasma gondii, which has a wide geographical distribution. The main infection routes are ingestion of cysts from raw or badly-cooked meat, ingestion of oocysts from substrates contaminated with the feces of infected felines and congenital transmission by tachyzoites. The congenital form results in a severe systemic disease, because if the mother is infected for the first time during gestation, she can present a temporary parasitemia that will infect the fetus. Many of the clinical symptoms are seen in congenitally-infected children, from a mild disease to serious signs, such as mental retardation. Early diagnosis during the pregnancy is highly desirable, allowing prompt intervention in cases of infection, through treatment of pregnant women, reducing the probability of fetal infection and consequent substantial damage to the fetus. Conventional tests for establishment of a fetal diagnosis of toxoplasmosis include options from serology to PCR. Prevention of human toxoplasmosis is based on care to avoid infection, understanding the disease and serological exams during gestation. Pregnant women should be tested serologically from three months gestation, until one month after childbirth. Inclusion of serology for congenital toxoplasmosis along with the basic Guthrie test for PKU is of fundamental importance for early diagnosis of infection and so that treatment is initiated, in order to avoid possible sequels in the infant.