Stability of sulfadiazine sugar-free oral suspensions for the treatment of congenital toxoplasmosis

Abstract This study aimed to develop and evaluate the stability of sulfadiazine sugar-free extemporaneous oral suspensions, focusing on treating congenital toxoplasmosis. The excipients were carefully chosen to obtain safe products for the pediatric population. Sulfadiazine suspensions (100 mg/ mL) were prepared from the raw material or tablets, stored in amber glass bottles at 5±3ºC, and evaluated at 0, 14, and 30 days. An ultra-performance liquid chromatographic method was developed and validated to assay the drug. The particle size ranged from 29.3 to 50.6 µm, with some variation over the study; pH values around 7.0 and non-Newtonian behavior were observed without modification in the period. Formulations showed a fast dissolution rate (>80% in 15 minutes) without variation over the study. The drug assay was about 100% of the label claimed throughout the study, demonstrating the chemical stability and the preparations' dose homogeneity. The microbiological investigation indicated that both preparations met the requirements for the microbial count and absence of pathogens. In conclusion, the developed formulations can be used for 30 days when stored under refrigeration. The oral suspensions produced are easy to prepare and contain safe components, providing an alternative for congenital toxoplasmosis treatment in children.

Real-time PCR in the diagnosis of congenital toxoplasmosis

ABSTRACT The diagnosis of congenital toxoplasmosis presents limitations and therefore new options are necessary. The analysis of amniotic fluid by real-time PCR has already proved effective for confirmation of fetal infection. However, its performance in other biological samples is not clear yet. The aim of this study is to better understand the role of real-time PCR in the blood of the mother and newborn as well as in the amniotic fluid and placenta in the diagnosis of congenital toxoplasmosis. This is a descriptive cohort study of pregnant women with toxoplasmosis followed up in Rio de Janeiro, Brazil. Real-time PCR was performed in samples of maternal blood, amniotic fluid, placenta, and blood of newborns. In addition, histopathological examination of placentas was performed, and data collected from babies were collected. 116 pregnant women were followed up and 298 samples were analyzed. One (0.9%) pregnant woman presented positive PCR in the blood, 3 (3.5%) in the amniotic fluid, 1 (2.3%) in the placenta and no newborn had positive PCR in the blood. Histopathological study was suggestive of toxoplasmosis infection in 24 (49%) placentas. Six (5.2%) newborns were diagnosed with congenital toxoplasmosis, and only cases with positive PCR in the amniotic fluid had correlation of the PCR result with the diagnosis of congenital infection. Both maternal and blood samples of new-borns and placenta did not prove to be promising in the diagnosis of congenital toxoplasmosis. Further studies are needed to evaluate the real role of molecular diagnosis in other biological materials rather than the amniotic fluid.

Profile of pregnant women and children accompanied due to T. gondii exposure at a referred healthcare center: What has changed in 10 years? / Perfil de gestantes e crianças acompanhadas por exposição ao Toxoplasma gondii num centro de referência: O que mudou 10 anos depois?

Abstract Objectives: to characterize the profile of pregnant women and newborns accompanied at a reference center for infectious-parasitic diseases, after the exposure of T. gondii, establishing comparisons with a previous study, in the same location, ten years ago. Methods: this is a retrospective cohort study, with a follow-up of four years (2016 to 2019), using the previous study carried out from 2002 to 2010 as a comparative for the variables assessed. Mothers who presented tests suggestive of seroconversion for the disease during prenatal care and their respective concepts, followed up over a year, were included. The chi-square test was used, assuming a significance level of 5% for the comparison of the groups in the two periods. Results: during the period from 2016 to 2019, 79 binomials were studied, whereas 58 binomials were accompanied in the previous period. Comparing both periods, the findings showed lower proportions of adolescents (p<0.001), with low schooling (p<0.001), with low serological testing (p<0.001) and with late or postnatal diagnosis (p<0.001). As to the children, the findings showed fewer changes in fundoscopy (p<0.001), strabismus (p=0.002), hepatomegaly (p=0.026) and any sequelae (p<0.001). Conclusion: a positive advance was observed regarding the care provided for the mother-child binomial affected by T. gondii, with a reduction in negative outcomes for the child. However, there are still challenges concerning the diagnosis and proper management of the disease.

Resumo Objetivos: caracterizar o perfil de gestantes e neonatos acompanhadas em um centro de referência em doenças infecto-parasitárias, após exposição ao Toxoplasma gondii, estabelecendo comparações em relação a estudo prévio, no mesmo local, há dez anos. Métodos: trata-se de estudo de coorte retrospectivo, com seguimento de quatro anos (2016 a 2019), servindo o estudo prévio realizado de 2002 a 2010 como comparativo para as variáveis estudadas. Foram incluídas mães que apresentaram durante o pré-natal exames sugestivos soroconversão para a doença e seus respectivos conceptos, acompanhados ao longo de um ano. Utilizou-se o teste qui-quadrado, assumindo-se nível de significância de 5% para a comparação dos grupos nos dois períodos. Resultados: durante o período de 2016 a 2019, foram estudados 79 binômios, enquanto no período anterior foram acompanhados 58 binômios. Comparando-se os dois períodos, em relação às mães, registraram-se menores proporções de adolescentes (p<0,001), de baixa escolaridade (p<0,001), baixa realização de testes sorológicos (p<0,001) e com diagnóstico tardio ou pós-natal (p<0,001). Em relação às crianças, verificaram-se menores proporções de alterações de fundoscopia (p<0,001), estrabismo (p=0,002), hepatomegalia (p=0,026) e qualquer sequela (p<0,001). Conclusão: observou-se um avanço em relação aos cuidados para o binômio mãe-filho acometido pelo T. gondii, com redução de desfechos negativos sobre a criança. Todavia, ainda existem desafios para o diagnóstico e adequado manejo da doença.

Toxoplasma gondii SAG2, SAG3 and GRA6 alleles and single nucleotide polymorphism in congenital infections with known parasite load and clinical outcome

ABSTRACT Amniotic fluid DNA samples were genotyped by multilocus-nested-PCR-RFLP, but only three of 11 markers amplified 113 of 122 (92.6%) samples, resulting in 12 untyped and 101 partial non-archetypal genotypes. The 101 typed samples were subdivided into four groups: G1 with 73 samples (5'and 3' SAG2 allele I + SAG3 allele III + GRA6 allele III), 53 had parasite load ≤ 102 parasites/mL (43 asymptomatic, 10 mild infections), 17 had load > 102 and ≤ 103 (one mild, 13 moderate and three severe), and three had load > 103 parasites/mL (three severe); G2 with 22 samples (5'and 3' SAG2 allele I + SAG3 allele III), all parasite load levels ≤ 102 parasites/mL (18 asymptomatic and four mild); G3 with five samples (5' and 3' SAG2 allele I + SAG3 allele II), parasite load ≤ 102 parasites/mL (three asymptomatic and two mild); G4 with one sample (5' and 3' SAG2 allele II + SAG3 allele II + GRA6 allele I), a parasite load < 102 parasites/mL in an asymptomatic infant. After DNA sequencing, restriction sites confirmed SAG2, SAG3 and GRA6 alleles in 98.7%, 100% and 100% of the cases, respectively, while single nucleotide polymorphisms confirmed 90% of 5'-SAG2 allele I; 98.7% of 3'-SAG2 allele I; 98% of SAG-3 allele III, but only 40% of GRA6 allele III results. For the moment, partial non-archetypal genotypes of parasites did not show any relationship with either parasite load in amniotic fluid samples or clinical outcome of infants at the age of 12 months.

Toxoplasmosis congénita con enfermedad neurológica severa en un hospital de referencia del Perú / Congenital toxoplasmosis with severe neurological disease in a referral hospital in Peru

RESUMEN El propósito del presente estudio fue describir las características epidemiológicas, clínicas, y terapéuticas de pacientes con diagnóstico de toxoplasmosis congénita (TC) con enfermedad neurológica severa. Se revisaron las historias clínicas de los pacientes menores de 1 año con serología IgM positiva para Toxoplasma gondii y compromiso encefálico, ocular y/o auditivo. El estudio se realizó en el Instituto Nacional de Salud del Niño San Borja (INSN-SB) en Lima, Perú. Se evaluaron a 21 pacientes con diagnóstico de TC, el 57,1% fueron del sexo femenino y la mediana de edad al momento del diagnóstico fue 3,1 meses (RIC: 1,7-7,3). Las principales manifestaciones del sistema nervioso central fueron hidrocefalia (76,2%), calcificaciones intracraneales (52,4%), microcefalia (42,9%), y convulsiones (25,6%); la manifestación ocular más frecuente fue la coriorretinitis (38,1%). En conclusión, 64% de los casos de TC tuvieron una o más manifestaciones de enfermedad neurológica severa.

ABSTRACT The aim of this study was to describe the epidemiological, clinical, and therapeutic characteristics of patients diagnosed with congenital toxoplasmosis (CT) with severe neurological disease. We reviewed the medical records of patients under 1 year of age with positive IgM test for Toxoplasma gondii and brain, eye, and/or hearing involvement. This study was carried out at the Instituto Nacional de Salud del Niño San Borja (INSNSB), Lima, Peru. Twenty-one patients diagnosed with CT were evaluated; 57.1% were female, and the median age at diagnosis was 3.1 months (IQR: 1.7-7.3). The main central nervous system manifestations were hydrocephalus (76.2%), intracranial calcifications (52.4%), microcephaly (42.9%), and convulsions (25.6%); the most frequent ocular manifestation was chorioretinitis (38.1%). In conclusion, 64% of CT cases had one or more manifestations of severe neurological disease.

Toxoplasmosis ocular en lactantes de 0 a 12 meses de edad con toxoplasmosis congénita / Ocular toxoplasmosis in infants 0 to 12 months of age with congenital toxoplasmosis

INTRODUCCIÓN: La toxoplasmosis ocular (TO) es una retinocoroiditis que evoluciona con varios episodios de inflamación y puede presentarse, tanto en la forma congénita o adquirida de la enfermedad, OBJETIVO: Describir la frecuencia y características clínicas de la TO en lactantes de 0 a 12 meses, hijos de madres con serología positiva para toxoplasmosis en el periodo perinatal. METODOLOGÍA: Estudio descriptivo transversal, ambispectivo. Ingresaron lactantes de 0 a 12 meses de edad, cuyas madres tenían serología positiva para toxoplasmosis en el periodo perinatal, remitidos al servicio de oftalmología pediátrica para evaluación. Se recogieron variables demográficas, serología materna y de los lactantes, y los resultados del examen oftalmológico. Los datos fueron analizados en SPSS-v21. RESULTADOS: El 46,4% de 125 lactantes tenían TO, de ellos, 67,2% era de sexo femenino (p = 0,04), la mediana de edad fue de 6 meses, el 41% tenía IgG e IgM positiva. Las lesiones fueron bilaterales en 82,8%, central en 86,2%, e inactivas en 81%. La retinocoroiditis se acompañó de estrabismo en 41%. CONCLUSIONES: La frecuencia de TO en esta población de lactantes con toxoplasmosis congénita, fue elevada. Más de 80% de las lesiones oculares eran inactivas, de localización central y compromiso bilateral.

BACKGROUND: Ocular toxoplasmosis (OT) is a retinochoroiditis that evolves with several episodes of inflammation and can occur both in the congenital or acquired form of the disease, AIM: To describe the frequency and clinical characteristics of OT in infants aged 0 to 12 months, children of mothers with positive serology for toxoplasmosis in the perinatal period. METHODS: Cross-sectional descriptive, ambispective study. RESULTS: Infants from 0 to 12 months of age, whose mothers had positive serology for toxoplasmosis in the perinatal period, referred to the pediatric ophthalmology service for evaluation, were admitted. Demographic variables, maternal and infant serology and the results of the ophthalmological examination were collected. Data were analyzed in SPSS v21 RESULTS: 46.4% of 125 infants had OT, of them 67.2% were female, (p = 0.04) the median age was 6 months, 41% had IgG and IgM positive. The lesions were bilateral in 82.8%, central in 86.2%, and inactive in 81%. Retinochoroiditis was accompanied by strabismus in 41%. CONCLUSIONS: The frequency of OT in this population of infants with congenital toxoplasmosis was high. more than 80% of the eye lesions were inactive, centrally located and bilaterally involved.

Toxoplasmosis congénita: la importancia de la adherencia a las guías y las implicaciones clínicas en Colombia / Congenital toxoplasmosis: the importance of adherence to guidelines and clinical implications in Colombia

Resumen Introducción: La toxoplasmosis congénita continúa siendo un problema de salud pública. Aun cuando existen guías plenamente divulgadas y conocidas, se observa poca implementación de ellas en algunas instituciones de salud y una inadecuada interpretación de las pruebas serológicas en las gestantes. Esto puede generar falta de captación y tratamiento en embarazadas con primoinfección por Toxoplasma gondii. Casos clínicos: Se reportan dos casos de toxoplasmosis congénita, uno de ellos con desenlace fatal. En ambos no se siguieron las guías de práctica clínica, lo cual conllevó un diagnóstico tardío y, en consecuencia, un manejo en condiciones inapropiadas con daños graves. Conclusiones: La toxoplasmosis es una infección congénita aún prevalente en algunos países, con secuelas graves, discapacidad neurológica y riesgo de daño ocular, incluso tardío. Además, existen algunas variedades de cepas de T. gondii con un comportamiento más agresivo en Latinoamérica, lo cual empeora la presentación de los casos e incluye mayor riesgo de muerte.

Abstract Background: Congenital toxoplasmosis continues to be a public health problem. Although clinical guidelines have been divulgated and are well known, they are not implemented in some health institutions, in addition of an inappropriate interpretation of the serological tests in pregnant women. This situation can lead to lack of screening and treatment in pregnant women with primary Toxoplasma gondii infection. Case reports: We report two cases of congenital toxoplasmosis, one with a fatal outcome. In both cases, the clinical guidelines were not initially followed, leading to a delayed diagnosis and, consequently, an inappropriate management in conditions with severe damage. Conclusions: Toxoplasmosis is a congenital infection still prevalent in some countries, with severe sequelae, neurological disability, and even late risk of ocular damage. Additionally, some varieties of the T. gondii strains have a more aggressive pattern in Latin America, worsening the clinical presentation of cases and including a high risk of death.

Consenso Argentino de toxoplasmosis congénita 2020 / Argentine Consensus of congenital toxoplasmosis

Resumen La transmisión vertical de la infección por Toxoplasma gondii ocurre cuando la madre se infecta por primera vez en el transcurso del embarazo. El diagnóstico de la infección materna y la del re cién nacido se logra con el conjunto de pruebas serológicas, hallazgos clínicos y ecográficos. El reconocimiento temprano de la infección materna permite un tratamiento que reduce la tasa de transmisión y el riesgo de daño en el producto de la concepción. El objetivo de este consenso de expertos fue revisar la literatura científica para actualizar las recomendaciones de práctica clínica respecto de la prevención, el diagnóstico y el tratamiento de la toxoplasmosis congénita en nuestro país.

Abstract Mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. Diag nosis of maternal infection and the newborn is achieved by a combination of serological tests, clinical features and ultrasound images. An early diagnosis of maternal infection allows treatment that offers a reduction both in transmission rate and risk of congenital damage. The aim of this expert consensus was to review the scientific literature which would enable an update of the clinical practice guideline of prevention, diagnosis and treatment of congenital toxoplasmosis in our country.

Comparison between Enzyme Immunoassays Performed on Samples of Dried Blood and Serum for Toxoplasmosis Prenatal Screening: Population-based Study / Comparação entre ensaios imunoenzimáticos realizados em amostras de sangue seco e soro para triagem prénatal da toxoplasmose: Estudo populacional

Abstract Objective Most prenatal screening programs for toxoplasmosis use immunoassays in serum samples of pregnant women. Few studies assess the accuracy of screening tests in dried blood spots, which are of easy collection, storage, and transportation. The goals of the present study are to determine the performance and evaluate the agreement between an immunoassay of dried blood spots and a reference test in the serum of pregnant women from a population-based prenatal screening program for toxoplasmosis in Brazil. Methods A cross-sectional study was performed to compare the immunoassays Imunoscreen Toxoplasmose IgM and Imunoscreen Toxoplasmose IgG (Mbiolog Diagnósticos, Ltda., Contagem, Minas Gerais, Brazil)in dried blood spots with the enzymelinked fluorescent assay (ELFA, BioMérieux S.A., Lyon, France) reference standard in the serum of pregnant women from Minas Gerais Congenital Toxoplasmosis Control Program. Results The dried blood spot test was able to discriminate positive and negative results of pregnant women when comparedwith the reference test, with an accuracy of 98.2% for immunoglobulin G (IgG), and of 95.8% for immunoglobulin M (IgM). Conclusion Dried blood samples are easy to collect, store, and transport, and they have a good performance,making this a promisingmethod for prenatal toxoplasmosis screening programs in countries with continental dimensions, limited resources, and a high prevalence of toxoplasmosis, as is the case of Brazil.

Resumo Objetivo A maioria dos programas de triagem pré-natal para toxoplasmose utiliza imunoensaios em amostras de soro de gestantes. Poucos estudos avaliam a acurácia dos testes de triagem em amostras de sangue seco, que são de fácil coleta, armazenamento e transporte. Este estudo teve como objetivo determinar o desempenho e avaliar a concordância entre um imunoensaio em sangue seco e um teste de referência em soro de gestantes de um programa de rastreamento pré-natal de base populacional para toxoplasmose no Brasil. Métodos Realizou-se um estudo transversal para comparar os imunoensaios Imunoscreen Toxoplasmose IgM e Imunoscreen Toxoplasmose IgG (Mbiolog Diagnósticos, Ltda., Contagem, Minas Gerais, Brazil) em sangue seco com o padrão de referência ensaio fluorescente ligado a enzimas (enzyme-linked fluorescent assay, ELFA, BioMérieux S.A., Lion, França) no soro de gestantes do Programa de Controle de Toxoplasmose Congênita de Minas Gerais. Resultados O exame em sangue seco foi capaz de discriminar os resultados positivos e negativos das gestantes quando comparado ao teste de referência, com acurácia de 98,2% para imunoglobulina G (IgG), e de 95,8% para imunoglobulina M (IgM). Conclusão O sangue seco apresenta bom desempenho e é uma amostra de fácil coleta, armazenamento e transporte, o que o torna um método promissor para programas de triagem pré-natal de toxoplasmose em países com dimensões continentais, recursos limitados, e alta prevalência de toxoplasmose, como é o caso do Brasil.

Conhecimento de médicos e enfermeiros atuantes no pré-natal sobre toxoplasmose / Conocimiento de médicos y enfermeros actuantes en prenatal sobre la toxoplasmosis / Knowledge of toxoplasmosis among doctors and nurses who provide prenatal care

RESUMO Objetivo: descrever o conhecimento de médicos e enfermeiros pré-natalistas sobre a toxoplasmose. Método: estudo transversal, analítico, realizado entre outubro de 2018 e fevereiro de 2019, com 89 profissionais de 43 Unidades Básicas de Saúde de Aracaju, Sergipe, Brasil, por meio de questionário autoaplicado. Foram calculadas as frecuências absolutas, relativas e os odds ratios. Utilizaram-se os testes Exato de Fischer e Qui-quadrado para análise dos dados. Resultados: os médicos e enfermeiros atuantes no pré-natal apresentaram pouco conhecimento sobre toxoplasmose relacionado às formas infectantes (p=1,000), vias de transmissão (p=1,000), grupo vulnerável (p=0,290), período de transmissão (p=1,000), maior risco para sequelas no recémnascido (p=0,828), quando realizar exames (p=0,015), indicação e interpretação do teste de avidez (p=0,355). Conclusão: este estudo identificou lacunas de conhecimento e poderá contribuir para planejamento de educação continuada para profissionais pré-natalistas, a fim de prevenir a toxoplasmose congênita.

RESUMEN: Objetivo: Describir el conocimiento de médicos y enfermeros de prenatal sobre la toxoplasmosis. Método: Estudio transversal, analítico, realizado entre octubre de 2018 y febrero de 2019, con 89 profesionales de 43 Unidades Básicas de Salud de Aracaju, Sergipe, Brasil, mediante cuestionario autocompletado. Se calcularon las frecuencias absolutas, relativas, y los odds ratios. Fueron utilizados para análisis de los datos los tests Exacto de Fischer y Chi-cuadrado. Resultados: Los médicos y enfermeros actuantes en el prenatal demostraron poco conocimiento sobre toxoplasmosis respecto a sus vías de infección (p=1,000), modos de transmisión (p=1,000), grupo vulnerable (p=0,290), período de contagiosidad (p=1,000), riesgo mayor de secuelas en el recién nacido (p=0,828), momento de realización de análisis (p=0,015), indicación e interpretación del test de avidez (p=0,355). Conclusión: El estudio identificó brechas de conocimiento, y contribuirá a planificar una educación continua para profesionales de prenatal, a efectos de prevenir la toxoplasmosis congénita.

ABSTRACT Objective: To describe the knowledge of doctors and nurses who provide prenatal care about toxoplasmosis. Method: Cross-sectional analytical study, conducted between October 2018 and February 2019, with 89 professionals from 43 Basic Health Units in Aracaju, State of Sergipe, in Brazil, through a self-administered questionnaire. Absolute and relative frequencies and odds ratios were calculated. Fischer Exact test and Chi-square test were used for data analysis. Results: Doctors and nurses who provide prenatal care have shown little knowledge about toxoplasmosis related to infectious forms (p = 1,000), transmission routes (p = 1,000), vulnerable group (p = 0,290), transmission period (p = 1,000), greater risk for complications in newborns (p = 0.828), when tests should be performed (p = 0.015), indication for performing and interpretation of the avidity test (p = 0.355). Conclusion: The present study identified knowledge gaps and may contribute to planning continuing education for prenatal care professionals, in order to prevent congenital toxoplasmosis.

Toxoplasmose congênita na atenção primária à saúde: importância da prevenção no controle de uma doença negligenciada / Congenital toxoplasmosis in primary health care: the importance of prevention in the control of a neglected disease / Toxoplasmosis congénita en la atención primaria de salud: importancia de la prevención en el control de una enfermedad desatendida

Justificativa e Objetivos: a toxoplasmose é uma doença com grande impacto na saúde pública, responsável por causar sequelas em recém-nascidos com a infecção, apesar de ainda ser negligenciada no Brasil. A doença é potencialmente grave quando há transmissão congênita. O diagnóstico da toxoplasmose durante a gestação é complexo e o tratamento da doença em gestantes não é totalmente eficaz. O presente estudo objetivou realizar um levantamento sobre o conhecimento de gestantes atendidas nas unidades básicas de saúde do município de Jataí/GO sobre a toxoplasmose. Métodos: promover ações educativas com gestantes sobre a doença e formas de prevenção. As ações foram realizadas por acadêmicos do curso de medicina da Universidade Federal de Jataí com 64 gestantes. Resultados: observou-se que faltam informações sobre a doença e formas de prevenção, sendo que 86% das gestantes não conheciam todas as formas de transmissão da toxoplasmose. As participantes relataram também não ter recebido instruções sobre a doença durante o acompanhamento pré-natal. Conclusão: o trabalho evidenciou a falta de informações sobre a toxoplasmose congênita por parte das gestantes, indicando que essas ações na atenção primária à saúde são extremamente valiosas para a prevenção da doença, além de contribuir para a formação de acadêmicos do curso de medicina.(AU)

Background and Objectives: toxoplasmosis is a disease with a great impact on public health, causing sequelae to infected newborns, however, this disease remains neglected in Brazil. The disease is potentially serious when there is congenital transmission. Toxoplasmosis diagnosis during pregnancy is complex and the treatment of the disease in pregnant women is not fully effective. This study aimed at surveying the knowledge of toxoplasmosis in pregnant women cared for at Basic Health Units in the city of Jataí/GO. Methods: to promote educational actions with pregnant women on the disease and forms of prevention. The actions were conducted by medical students from the Universidade Federal de Jataí and includes 64 pregnant women. Results: we observed a lack of information about the disease and its prevention, and 86% of them did not know all forms of transmission of toxoplasmosis. It was also evident that pregnant women report not receiving instructions about the disease during prenatal care. Conclusion: our study evidenced the lack of information on congenital toxoplasmosis in pregnant women, indicating that these actions in primary care are extremely valuable to prevent the disease, in addition to contributing to the training of medical students.(AU)

Justificación y Objetivos: la toxoplasmosis es una enfermedad con un gran impacto en la salud pública, causante de secuelas en recién nacidos con esta infección, a pesar de que todavía se descuida en Brasil. La enfermedad es potencialmente grave cuando hay transmisión congénita. El diagnóstico de toxoplasmosis durante el embarazo es complejo, y el tratamiento de la enfermedad en mujeres embarazadas no es totalmente efectivo. Este estudio tuvo como objetivo llevar a cabo una encuesta sobre el conocimiento de la toxoplasmosis en mujeres embarazadas atendidas en las unidades básicas de salud en la ciudad de Jataí, estado de Góias (Brasil). Métodos: promover acciones educativas sobre la enfermedad con mujeres embarazadas y las formas de prevención. Las acciones fueron realizadas por estudiantes de medicina de la Universidade Federal de Jataí con 64 mujeres embarazadas. Resultados: existe una falta de información sobre la enfermedad y las formas de prevenirla, y el 86% de ellas no conocían todas las formas de transmisión de toxoplasmosis. También fue evidente que las mujeres embarazadas informaron que no recibieron instrucciones sobre la enfermedad durante la atención prenatal. Conclusión: el estudio puso de manifiesto la falta de información sobre la toxoplasmosis congénita por parte de las mujeres embarazadas, lo que indica que estas acciones en atención primaria son muy valiosas para prevenir la enfermedad, además de contribuir a la formación de estudiantes de medicina.(AU)

Investigation on seroprevalence of Toxoplasma gondii infections among neonates in Fujian Province / 中国血吸虫病防治杂志

Objective To investigate the seroprevalence of Toxoplasma gondii infections among neonates in Fujian Province, so as to provide insights into the development of interventions for the prevention and control of congenital toxoplasmosis. Methods A total of 1 045 neonates delivered in Fujian Province from 2017 to 2018 were recruited, including 387 preterm infants and 658 full-term infants. Umbilical cord blood was sampled from all neonates, and the seroprevalence of anti-T. gondii IgG antibody was detected and compared between preterm and full-term infants. In addition, elbow venous blood samples were collected from neonates’mothers, and the seroprevalence of anti-T. gondii IgG antibody was detected and compared between preterm and full-term infants’mothers. Results The overall seroprevalence of anti-T. gondii IgG antibody was 9.38% among the 1 045 neonates in Fujian Province. The seroprevalence of anti-T. gondii IgG antibody was 18.35% in the 387 preterm infants, and there was no significant difference in the seroprevalence of anti-T. gondii IgG antibody between male and female infants (17.69% vs. 18.75%, χ2 = 0.07, P > 0.05). The seroprevalence of anti-T. gondii IgG antibody was 4.10% in the 658 full-term infants, and there was no significant difference in the seroprevalence of anti-T. gondii IgG antibody between male and female infants (4.14% vs. 4.08%, χ2 = 0, P > 0.05). In addition, the overall seroprevalence of anti-T. gondii IgG antibody was 15.02% in all neonates’ mothers, and the seroprevalence was significantly greater in preterm infants’mothers than in full-term infant’s mothers (20.93% vs. 11.55%, χ2 = 16.79, P < 0.01). Conclusions The seroprevalence of T. gondii infections is significantly higher in preterm infants and their mothers than in full-term infants and their mothers. Prenatal detection of T. gondii infections and health education pertaining to toxoplasmosis prevention and control knowledge are required to be strengthened to effectively reduce the incidence of congenital toxoplasmosis.

Prevalencia de anticuerpos anti-Toxoplasma gondii en embarazadas en siete hospitales de Buenos Aires: Comparación entre 2006 y 2017 / Prevalence of anti-Toxoplasma gondii antibodies in pregnant women in seven hospitals in Buenos Aires area. Comparison 2006 vs. 2017

Se analizó; de forma retrospectiva la presencia de anticuerpos só;©ricos IgG e IgM anti-Toxoplasma gondii en las embarazadas que concurrieron a siete hospitales del ó;rea Metropolitana de Buenos Aires durante 2006 y 2017. La prevalencia de infecció;n, medida como presencia de anticuerpos, en 2006 vs. 2017, fue: Hospital Alemán: 22 y 17% (p = 0.004), Hospital Fiorito: 44 y 33% (p < 0.001), Hospital Gandulfo: 30 y 34% (p 0.025), Hospital Grierson: 60 y 44% (p < 0.001), Hospital Rivadavia: 59 y 51% (p=0.003), Maternidad Sardá 47 y 39% (p < 0.001) y Hospital Thompson: 61 y 51% (p < 0.001). La comparació;n demostró; una disminució;n estadísticamente significativa de la seroprevalencia en seis hos pitales. Tambín disminuyeron significativamente la reactividad para IgM en 2017 respecto de 2006 y la seroprevalencia para T. gondii en el total de la població;n de embarazadas estudiadas, lo que significa un mayor nó;ºmero de mujeres susceptible de desarrollar infecció;n aguda durante el embarazo.

We analyzed the presence of IgG and IgM anti- Toxoplasma gondii, as a measure of infection, in pregnant women attending seven hospitals in the Metropolitan Area of Buenos Aires during 2006 and 2017. T. gondii seroprevalence in 2006 vs. 2017, was: Hospital Alemán: 22 and 17% (p = 0.004), Hospital Fiorito: 44 and 33% (p < 0.001), Hospital Gandulfo: 30 and 34% (p 0.025), Hospital Grierson 60 and 44% (p < 0.001), Hospital Rivadavia: 59 and 51% (p = 0.003), Hospital Sardá: 47 and 39% (p < 0. 001), and Hospital Thompson: 61 and 51% (p < 0.001). The comparison showed a significant decrease in seroprevalence in six hospitals. We also observed a significant decrease in the reactivity for IgM in 2017 compared to 2006 and in the seroprevalence for T. gondii in the overall population of pregnant women in the study. This means that a greater number of women are susceptible to develop acute infection during pregnancy.

Follow-up of toxoplasmosis during pregnancy: ten-year experience in a University hospital in southern Brazil / Acompanhamento da toxoplasmose durante a gravidez: uma década de experiência em um hospital universitário no Sul do Brasil

Abstract Objective To describe a population of pregnant women diagnosed with toxoplasmosis and their respective newborns, describing the hospital protocol for treatment and follow-up. Methods Retrospective cohort of pregnant women with acute toxoplasmosis infection and risk of transplacental transmission who were sent to the Fetal Medicine Group of Hospital de Clínicas de Porto Alegre (HCPA) between - January 1, 2006 and December 31, 2016. All patients with confirmed disease were included. The diagnostic protocol and treatment were applied; a polymerase chain reaction (PCR) analysis of the amniotic fluid was used to diagnose toxoplasmosis and determine the treatment. The newborns were followed up at the pediatric outpatient clinic specializing in congenital infection. The patients who were not followed up or were not born in the HCPA were excluded. Results A total of 65 patients were confirmed to have gestational toxoplasmosis; 40 performed amniocentesis, and 6 (15%) were identified as having positive PCR in the amniotic fluid. In five of those cases, this result associated with the gestational age defined the triple therapy during pregnancy, and in one case, it defined the monotherapy (advanced gestational age). A total of 4 of these newborns were treated from birth with triple therapy for 10months, 1 was not treated (due to maternal refusal), and 1 progressed to death within the first 54 hours of life due to complications of congenital toxoplasmosis. Of the 34 remaining cases with a negative PCR, 33 were treated with monotherapy and 1 was treated with triple therapy (ultrasound findings); of these children, 9 (26.5%) presented negative immunoglobulin G (IgG), 24 (70.6%) presented positive IgG (but none presented positive immunoglobulin M [IgM]), and 1 (2,9%) presented alterations compatible with congenital disease and started treatment with the triple therapy soon after birth. Out of the total sample of 60 patients, among the 25 who did not perform amniotic fluid PCR, 5 were treated with triple therapy (ultrasound findings/prior treatment) and 20 patients were submitted to monotherapy; only two newborns underwent treatment for congenital toxoplasmosis. Among the 65 cases of gestational toxoplasmosis, 6 (9,2%) children had a diagnosis of congenital toxoplasmosis, and 2 patients with triple therapy felt severe adverse effects of the medications. Conclusions The present study suggests that research on PCR screening of the amniotic fluid may be useful to identify patients with a higher potential for fetal complications, who may benefit from the poly-antimicrobial treatment. Patients with negative PCR results must continue to prevent fetal infection with monotherapy, without risk of fetal or maternal impairment.

Resumo Objetivo Descrever uma população de pacientes diagnosticadas com toxoplasmose na gestação e seus respectivos recém-nascidos, relatando o protocolo do hospital durante o tratamento e seguimento. Métodos Coorte retrospectiva de gestantes com infecção aguda por toxoplasmose e risco de transmissão transplacentária, encaminhadas para acompanhamento pelo Grupo deMedicina Fetal doHospital de Clínicas de Porto Alegre (HCPA) entre 1o de janeiro de 2006 e 31 de dezembro de 2016. Todas as pacientes comdoença confirmada foram incluídas. O protocolo de diagnóstico e tratamento foi aplicado; uma análise da reação em cadeia da polimerase (RCP) no líquido amniótico foi utilizada para diagnosticar a toxoplasmose e determinar o tratamento. Os recém-nascidos foram acompanhados no ambulatório de pediatria especializadoeminfecções congênitas. Pacientes que não foramseguidas ou cujo parto não foi feito no hospital foram excluídas. Resultados A toxoplasmose gestacional foi confirmada em 65 pacientes; 40 realizaram amniocentese, e 6 (15%) foram identificadas com RCP positiva no líquido amniótico. Este resultado associado à idade gestacional definiu a terapia tríplice durante a gestação em 5 casos, e a monoterapia em 1 caso (por idade gestacional avançada). Quatro destas crianças foram tratadas desde o nascimento com terapia tríplice por 12 meses, 1 não foi tratada (por recusa materna), e 1 evoluiu com óbito dentro das primeiras 54 horas de vida devido a complicações da toxoplasmose congênita. Dos 34 casos remanescentes com RCP negativa, 33 foram tratados com monoterapia, e 1 foi tratado com terapia tríplice (por achados ultrassonográficos); destes recém-nascidos, 9 (26,5%) tiveram imunoglobulina G (IgG) negativa, 24 (70,6%) tiveram IgG positiva, mas nenhum apresentou imunoglobulina M (IgM) positiva, e 1 (2,9%) apresentou alterações compatíveis comdoença congênita e iniciou a terapia tríplice logo após o nascimento. Entre as 25 pacientes que não fizeram RCP no líquido amniótico, 5 foram tratadas com terapia tríplice (por achados ultrassonográficos/ tratamento prévio) e 20 receberam monoterapia; somente 2 recém-nascidos receberam tratamento para toxoplasmose congênita. Entre os 65 casos de toxoplasmose gestacional, 6 (9,2%) recém-nascidos tiveram o diagnóstico de toxoplasmose congênita. Um total de 2 pacientes submetidas à terapia tríplice apresentaram efeitos adversos severos das medicações utilizadas. Conclusão Este estudo sugere que a triagem da RCP para toxoplasmose do líquido amniótico pode ser útil no rastreamento de pacientes com maior potencial para complicações fetais, que podem se beneficiar do tratamento poli antimicrobiano. Pacientes com RCP negativa devem continuar a prevenir a infecção fetal com monoterapia, sem risco de comprometimento fetal ou materno.

Study of brainstem auditory evoked potentials in early diagnosis of congenital toxoplasmosis / Estudo dos potenciais auditivos de tronco encefálico na toxoplasmose congênita diagnosticada precocemente

Abstract Introduction: Congenital toxoplasmosis is an infectious disease with high prevalence in tropical countries. It is characterized by neurological, ophthalmological and auditory sequelae. Objective: The aim of this study was to evaluate and describe the brainstem auditory evoked potential in infants aged 1-3 months diagnosed with congenital toxoplasmosis and to compare them with infants of the same age group without the infection. Methods: This is an observational, analytical and cross-sectional study in which brainstem auditory evoked potential was investigated in infants with congenital toxoplasmosis. The following audiological exams were performed: transient-evoked otoacoustic emissions, clinical and automatic brainstem auditory evoked potential. Results: 100 children participated in the study, but the final sample consisted of 76 children. Of the 37 children with toxoplasmosis included in the study, 28 completed the neurological imaging evaluation, and of these, 3 (10.7%) showed an altered neurological examination. At the brainstem auditory evoked potential assessment, two children without toxoplasmosis and 10 children with congenital toxoplasmosis had results suggestive of alterations in the brainstem auditory pathway maturation. Conclusion: 10 (27%) children were identified with a possible unilateral alteration in the electrophysiological assessment. There was a 5-fold higher risk for a child between 1 and 3 months of age with toxoplasmosis to have an altered brainstem auditory evoked potential compared to a child of the same age range without the infection.

Resumo Introdução: A toxoplasmose congênita é uma doença infecciosa com grande prevalência nos países tropicais. Caracteriza-se por sequelas neurológicas, oftalmológicas e auditivas. Objetivo: O objetivo desse estudo foi avaliar e descrever o potencial evocado auditivo de tronco encefálico em bebês de 1 a 3 meses diagnosticados com toxoplasmose congênita e comparar com bebês de mesma faixa etária sem a infecção. Metódo: Trata-se de um estudo observacional, analítico e transversal, no qual foi realizada a pesquisa do potencial evocado auditivo de tronco cerebral em lactentes com toxoplasmose congênita. Foram realizados os exames audiológicos: emissões otoacústicas evocadas por estímulo transiente, potencial auditivo de tronco encefálico clínico e automático. Resultados: Participaram do estudo 100 crianças, porém a amostra final foi constituída por 76. Das 37 crianças com toxoplasmose incluídas no estudo, 28 completaram a avaliação neurológica de imagem e, dessas, três (10,7%) apresentaram exame neurológico alterado. Na avaliação do potencial evocado auditivo de tronco encefálico, duas crianças sem toxoplasmose e 10 com toxoplasmose congênita apresentaram resultado sugestivo de alteração no processo maturacional da via auditiva de tronco encefálico. Conclusão: Foram identificadas 10 (27%) crianças com possível alteração unilateral na avaliação eletrofisiológica e um risco cinco vezes maior de uma criança entre um e três meses com toxoplasmose apresentar alteração no potencial evocado auditivo de tronco encefálico quando comparada com uma criança da mesma faixa de idade sem a infecção.

Evaluation of functionality in children aged 4-6 years presenting congenital toxoplasmosis and retinochoroiditis / Avaliação da funcionalidade em crianças de 4-6 anos apresentando toxoplasmose congênita e retinocoroidite

Abstract Introduction: In Brazil, congenital toxoplasmosis (CT) is the main cause of visual impairment in childhood. It causes retinochoroiditis, which should lead to blindness. Minas Gerais has a prevalence of 1 newborn with congenital toxoplasmosis for every 770 live births. Objective: To evaluate visual functionality and tasks of self-care with TC classified in groups according to a visual acuity. Method: A cross-sectional study with 96 preschoolers with CT. Ophthalmologic examination and assessment of some functionalities were performed: The Functional Vision Evaluation (AVIF-2 at 6 years) and the Pediatric Disability Assessment Inventory (PEDI-Brazilian version). Results: Children were classified into three groups according to visual acuity: moderate / severe visual loss (n=16), low level (n=39) and normal vision (n=41). The chance of difference is not greater than AVIF-2 at 6 years among the three groups (p=0.001), being (p <0.0001) between the groups with moderate/severe visual and normal vision. The domain scores are displayed as the end result (p=0.022). The test PEDI is not able to make a difference between the groups. It is not different between the scores of the tests carried out. Conclusion: Children with CT without moderate / severe visual impairment, compromising visual functionality with greater impairment without visual accompaniment. The AVIF-2 at 6 years test demonstrated the impairment between groups with different visual acuities. The PEDI (self-care) test was not performed with a significant difference in scores between the groups. The AVIF-2 at 6 years test may contribute to the more effective intervention in the visual habilitation of children with CT and low vision.

Resumo Introdução: No Brasil, a toxoplasmose congênita (TC) é a principal causa de deficiência visual na infância. É causa de retinocoroidite, que pode levar à cegueira. Minas Gerais apresenta prevalência de um neonato com TC para cada 770 nascidos vivos. Objetivo: Avaliar funcionalidade visual e tarefas do autocuidado de crianças com TC classificadas em grupos de acordo com a acuidade visual. Método: Estudo transversal com 96 pré-escolares com TC. Realizado exame oftalmológico e avaliada a funcionalidade por dois instrumentos: O teste Avaliação da Visão Funcional (AVIF-2 a 6 anos) e Inventário de Avaliação Pediátrica de Incapacidade (PEDI-versão brasileira). Resultados: As crianças foram classificadas em três grupos conforme a acuidade visual: perda visual moderada/grave (n=16), perda leve (n=39) e visão normal (n=41). Houve diferença significativa no escore total do AVIF-2 a 6 anos entre os três grupos (p=0,001), e entre os grupos com perda visual moderada/grave e visão normal (p<0,0001). Os escores do domínio seguimento visual apresentaram pior resultado (p=0,022). O teste PEDI não mostrou diferença significativa entre os grupos. Não houve correlação entre os escores dos testes aplicados. Conclusão: Crianças com TC e perda visual moderada/grave apresentaram comprometimento da funcionalidade visual com maior prejuízo no seguimento visual. O teste AVIF-2 a 6 anos demonstrou esse comprometimento entre os grupos com diferentes acuidades visuais. O teste PEDI (autocuidado) não mostrou diferença estatística significativa dos escores entre os grupos. O teste AVIF- 2 a 6 anos pode contribuir para intervenção mais objetiva na habilitação visual de crianças com TC e baixa visão.

Toxoplasmosis congénita, una mirada en la actualidad del tratamiento; revisión de la literatura / Congenital toxoplasmosis, a look at contemporary treatment; literature review / Toxoplasmose congênita, um olhar atual no tratamento; revisão de literatura

Introducción. La Toxoplasmosis congénita constituye una causa significativa de morbi-mortalidad neonatal en países de bajos ingresos como Colombia. Puede originar prematuridad, secuelas patológicas y pérdida fetal. El tamizaje en las gestantes y, a su vez, un tratamiento oportuno y adecuado disminuye la transmisión vertical y sus nefastas secuelas. El objetivo es presentar evidencia científica actualizada sobre el tratamiento farmacológico de la Toxoplasmosis Congénita. Metodología. Se realizó una búsqueda no sistemática en bases de datos: Pubmed, Medline, Clinical Key y Springer. Se incluyeron artículos originales y de revisión de tema publicados desde enero de 2014 hasta abril de 2019. División de los temas tratados. se abordan la fisiopatología y clínica, el abordaje diagnóstico, alternativas de prevención y tratamiento. Conclusiones. En la actualidad la terapia farmacológica es limitada, los esquemas de manejos se basan en espiramicina o la combinación de sulfadiazina/pirimetamina y ácido folínico; estas moléculas no son del todo bien toleradas y presentan un amplio espectro de reacciones adversas secundario a sus efectos tóxicos; resulta necesario la ejecución de estudios aleatorizados para evaluar su efectividad. Cómo citar: Rueda-Paez YS, Valbuena-Ruiz L, Quintero-Pimiento N, Pinilla-Plata A, Sayago-Silva J. Toxoplasmosis congénita, una mirada en la actualidad del tratamiento; revisión de la literatura. MedUNAB. 2019;22(1):51-63. doi: 10.29375/01237047.2612

Introduction. Congenital Toxoplasmosis constitutes a significant cause of neonatal morbimortality in underdeveloped countries like Colombia. It can cause prematurity, pathological after-effects and fetal loss. Screening expectant mothers and in turn, a timely and adequate treatment, reduce vertical transmission and its devastating effects. The objective is to present up-to-date scientific evidence about the pharmacological treatment of Congenital Toxoplasmosis. Methodology. A non-systematic search of databases was conducted: Pubmed, Medline, Clinical Key and Springer. Original and topic review articles were included dating from January 2014 to April 2019. Division of topics covered. Physiopathology and clinical pathology, diagnostic approach, prevention and treatment alternatives were addressed. Conclusions. At this time, pharmacological therapy is limited, management schemes are based on spiramycin or a combination of sulfadiazine/pyrimethamine and folinic acid; these molecules are not very well tolerated and exhibit a wide spectrum of adverse reactions apart from their toxic effects, thus it is necessary to conduct randomized studies to evaluate its effectiveness. Cómo citar: Rueda-Paez YS, Valbuena-Ruiz L, Quintero-Pimiento N, Pinilla-Plata A, Sayago-Silva J. Toxoplasmosis congénita, una mirada en la actualidad del tratamiento; revisión de la literatura. MedUNAB. 2019;22(1):51-63. doi: 10.29375/01237047.2612

Introdução. A toxoplasmose congênita é uma causa significativa de morbidade e mortalidade neonatal em países de baixa renda, como a Colômbia. Pode causar prematuridade, sequelas patológicas e perda fetal. A triagem em gestantes e, por sua vez, um tratamento oportuno e adequado diminui a transmissão vertical e suas consequências desastrosas. O objetivo é apresentar evidências científicas atualizadas sobre o tratamento farmacológico da Toxoplasmose Congênita. Metodologia. Foi realizada uma revisão não sistemática nas bases de dados: Pubmed, Medline, Clinical Key e Springer. Foram incluídos tanto artigos originais, quanto revisões de tópicos publicados de janeiro de 2014 até abril de 2019. Divisão dos tópicos discutidos. foram abordadas a fisiopatologia e a clínica, a abordagem diagnóstica, alternativas para prevenção e tratamento. Conclusões. Atualmente, a terapia farmacológica é limitada, os esquemas terapéuticos baseiam-se na espiramicina ou na combinação de sulfadiazina/pirimetamina e ácido folínico; estas moléculas não são totalmente toleradas e apresentam um amplo espectro de reações adversas secundárias aos seus efeitos tóxicos. É necessário realizar estudos randomizados para avaliar sua eficácia. Cómo citar: Rueda-Paez YS, Valbuena-Ruiz L, Quintero-Pimiento N, Pinilla-Plata A, Sayago-Silva J. Toxoplasmosis congénita, una mirada en la actualidad del tratamiento; revisión de la literatura. MedUNAB. 2019;22(1):51-63. doi: 10.29375/01237047.2612

Microcefalia por toxoplasmose congênita em tempos de epidemia por Zika vírus no Brasil / Microcephaly due to congenital toxoplasmosis in times of Zika virus epidemic in Brazil

Descreve-se um caso de toxoplasmose congênita com microcefalia, ocorrido durante a epidemia de Zika vírus no Brasil e somente diagnosticado como toxoplasmose aos sete meses de idade. Este caso ilustra a pertinência e urgência para a implementação de políticas públicas específicas para prevenção, diagnóstico e tratamento para a toxoplasmose adquirida durante a gestação, e demonstra que quando o assunto é microcefalia por infecções congênitas no Brasil, precisamos estar atentos a outras possibilidades além da infecção por Zika vírus; em especial à toxoplasmose congênita, que é altamente prevalente em nosso país, e se for diagnosticada e tratada no devido tempo, danos neurológicos e oculares irreversíveis poderão ser evitados. Apoiamos integralmente a portaria do Ministério da Saúde que torna obrigatória a notificação de casos de toxoplasmose gestacional e congênita no Brasil. As ações que venham a ser implementadas deverão resultar em um programa nacional específico para toxoplasmose gestacional e congênita, que possa beneficiar crianças em todo o país por meio de medidas de educação preventiva em saúde, da triagem e do tratamento para gestantes e recém nascidos.

A case of congenital toxoplasmosis with microcephaly, occurred during the epidemic of Zika virus in Brazil, and only diagnosed as toxoplasmosis at seven months of age, is described. This case illustrates the pertinence and urgency for the implementation of specific public policies for prevention, diagnosis and treatment for toxoplasmosis acquired during pregnancy, and shows that when the subject is microcephaly due to congenital infections in Brazil, one must be attentive to other possibilities besides Zika virus infection; in particular to congenital toxoplasmosis, which is highly prevalent in our country, and if diagnosed and treated in due course, irreversible neurological and ocular damage may be avoided. We fully support the Ministry of Health ordinance that makes it compulsory to notify cases of gestational and congenital toxoplasmosis in Brazil. The actions that will be implemented should result in a specific national program for gestational and congenital toxoplasmosis, which will benefit children throughout the country through preventive health education, screening and treatment for pregnant women and newborns.

Anomalias congênitas e suas principais causas evitáveis: uma revisão / Congenital anomalies and its main avoidable causes: a review

As anomalias congênitas (AC) podem ser definidas como todas as alterações funcionais ou estruturais do desenvolvimento fetal, cuja origem ocorre antes do nascimento. Elas possuem causas genéticas, ambientais ou desconhecidas. As principais causas das anomalias são os transtornos congênitos e perinatais, muitas vezes associados a agentes infecciosos deletérios à organogênese fetal, tais como os vírus da rubéola, da imunodeficiência humana (HIV), o vírus Zika, o citomegalovírus; o Treponema pallidum e o Toxoplasma gondii. O uso de drogas lícitas e ilícitas, de medicações teratogênicas, endocrinopatias maternas também podem ser citados como causa de AC. Estima-se que 15 a 25% ocorram devido às alterações genéticas, 8 a 12% são causadas por fatores ambientais e 20 a 25% podem ser causadas tanto por alterações genéticas quanto por fatores ambientais. Neste artigo, serão abordadas as principais causas das AC, com foco naquelas que podem ser evitadas. (AU)

Congenital anomalies (CA) can be defined as all functional or structural changes of fetal development that originate before birth. They have genetic, environmental or unknown causes. The main causes of anomalies are congenital and perinatal disorders, often associated with infectious agents deleterious to fetal organogenesis, such as rubella virus, human immunodeficiency virus (HIV), Zika virus, cytomegalovirus; the Treponema pallidum and the Toxoplasma gondii. The use of licit and illicit drugs, teratogenic medications, and maternal endocrinopathies can also be cited as causes of CA. It is estimated that 15 to 25% occur due to genetic alterations, 8 to 12% are caused by environmental factors and 20 to 25% can be caused by both genetic and environmental changes. In this article, the main causes of CA will be addressed, focusing on those that can be avoided. (AU)

Toxoplasmosis congénita: Diagnóstico serológico, RPC, aislamiento y caracterización molecular de Toxoplasma gondii / Congenital toxoplasmosis: Serology, PCR, parasite isolation and molecular characterization of Toxoplasma gondii

Resumen Introducción El diagnóstico de toxoplasmosis congénita (TC) en el recién nacido es muy importante porque debe recibir tratamiento siempre, sintomático o no, para evitar o aminorar las secuelas de la enfermedad. Objetivo Evaluación comparativa de los métodos disponibles en la institución para el diagnóstico de TC. Materiales y Métodos Se evaluaron métodos diagnósticos en 67 niños cuyas madres cursaron toxoplasmosis aguda durante el embarazo. Se utilizó la técnica de Sabin Feldman para IgG al nacimiento y durante el seguimiento serológico hasta el año de vida. Para determinar IgM, IgA e IgE se utilizó la técnica immunosorbent agglutination assay (ISAGA). El diagnóstico directo se realizó por reacción de polimerasa en cadena (RPC), aislamiento y caracterización molecular del parásito. Resultados La sensibilidad (S) de ISAGA IgM fue 87%, ISAGA IgA 91% y la especificidad (E) fue 100% para ambas; cuando se realizaron en conjunto, la S aumentó a 98%. La detección de IgE contribuyó al diagnóstico cuando se la detectó sólo en la sangre del neonato y no en sangre materna. Se aisló el parásito en cuatro casos de TC, uno fue genotipo II y los otros tres, genotipos "atípicos". La S del aislamiento fue 80% y la E 100%. Conclusión Los métodos serológicos utilizados mostraron una buena eficacia diagnóstica. Un caso fue detectado sólo por el aislamiento y la caracterización molecular tiene gran valor epidemiológico.

Background. Congenital toxoplasmosis diagnosis in the newborn is a very important issue due to the need for early treatment to prevent future sequels. Aim To compare available methods at the institution for the diagnosis of congenital toxoplasmosis. Material and Methods In this study we have evaluated the different diagnostic tests used in 67 congenital exposed newborns, including serological tests, PCR, parasite isolation and molecular characterization. Results The ISAGA IgM and IgA tests showed sensitivity (Se) of 87 and 91%, respectively, and specificity (Sp) of 100%. When ISAGA IgM and IgA were performed simultaneously, the Se increased to 98% and the Sp was 100%. The presence of IgE contributed to the diagnosis when it was detected in the child's serum but not in maternal blood. In four congenital infected children the parasite was isolated and genotyped: one was genotype II and the other three were "atypical" genotypes. No parasite was isolated in children without congenital toxoplasmosis. Discussion Overall, serological tests showed a good diagnostic performance although in one case they were all negative and isolation was the only tool to identify the infection. We conclude that it is essential to use all diagnostic tests in every single exposed child, including if possible, molecular characterization due to its epidemiological implication.