Maternal and congenital toxoplasmosis in Mayotte: Prevalence, incidence and management.

BACKGROUND: Toxoplasmosis is an infection caused by an intracellular protozoan, Toxoplasma gondii. It is usually asymptomatic, but toxoplasmosis acquired during pregnancy can cause congenital toxoplasmosis, potentially resulting in fetal damage. Epidemiological information is lacking for toxoplasmosis in Mayotte (a French overseas territory). We evaluated (1) the prevalence of maternal toxoplasmosis, (2) the incidence of maternal and congenital toxoplasmosis, and (3) the management of congenital toxoplasmosis in Mayotte. METHODOLOGY / PRINCIPAL FINDINGS: We collected all the available data for toxoplasmosis serological screening during pregnancy and maternal and congenital cases of toxoplasmosis obtained between January 2017 and August 2019 at the central public laboratory of Mayotte (Mamoudzou). Using toxoplasmosis serological data from samples collected from 16,952 pregnant women we estimated the prevalence of toxoplasmosis in Mayotte at 67.19%. Minimum maternal toxoplasmosis incidence was estimated at 0.29% (49/16,952, 95% CI (0.0022-0.0038)), based on confirmed cases of maternal primary infection only. The estimated incidence of congenital toxoplasmosis was 0.09% (16/16,952, 95% CI (0.0005-0.0015). Missing data made it difficult to evaluate management, but follow-up was better for mothers with confirmed primary infection and their infants. CONCLUSIONS / SIGNIFICANCE: The seroprevalence of toxoplasmosis among pregnant women and the incidence of toxoplasmosis are higher in Mayotte than in mainland France. There is a need to improve the antenatal toxoplasmosis screening and prevention programme, providing better information to physicians and the population, to improve management and epidemiological monitoring.

Prevention of congenital toxoplasmosis in France using prenatal screening: A decision-analytic economic model.

BACKGROUND: Toxoplasma gondii is one of the world's most common parasites. Primary infection of the mother during pregnancy can lead to transmission to the fetus with risks of brain and eye lesions, which may cause lifelong disabilities. France instituted a national program based on monthly retesting of susceptible pregnant women to reduce the number of severe cases through prompt antenatal and postnatal treatment and follow-up. OBJECTIVE: To evaluate the ability of the French prenatal retesting program to reduce the lifetime costs of congenital toxoplasmosis. METHODS: We measured and then compared the costs and benefits of screening vs. not screening using decision-tree modelling. It included direct and indirect costs to society of treatment and care, and the lifetime lost earnings of children and caregivers. A probabilistic sensitivity analysis was carried out. FINDINGS: Total lifetime costs per live born child identified as congenitally infected were estimated to be €444 for those identified through prenatal screening vs €656 for those who were not screened. Estimates were robust to changes in all costs of diagnosis, treatment, and sequelae. INTERPRETATION: Screening for the prevention of the congenital T. gondii infection in France is cost saving at €212 per birth. Compared with no screening, screening every pregnant woman in France for toxoplasmosis in 2020 would have saved the country €148 million in addition to reducing or eliminating the devastating physical and emotional suffering caused by T. gondii. Our findings reinforce the conclusions of other decision-analytic modelling of prenatal toxoplasmosis screening.

The epidemiology and disease burden of congenital TORCH infections among hospitalized children in China: A national cross-sectional study.

BACKGROUND: Congenital TORCH (Toxoplasma gondii (T. gondii), rubella virus (RV), cytomegalovirus (CMV), and herpes simplex virus (HSV)) infections are associated with a variety of adverse prenatal and neonatal events, including miscarriage, malformations and developmental abnormalities, and they remain an issue that cannot be neglected in China. However, the current research focuses more on the general screening of TORCH in women of childbearing age, and the medical information of children hospitalized due to congenital and perinatal TORCH infections has not been described in detail. This study summarized and analyzed the epidemiological characteristics, clinical manifestations, length of stay (LOS), and the disease burden of hospitalized children diagnosed with congenital TORCH infections in 27 children's hospitals in China. METHODOLOGY: Based on the face sheet of discharge medical records (FSMRs) of hospitalized children in 27 tertiary children's hospitals collected in the Futang Research Center of Pediatric Development and aggregated into FUTang Update medical REcords (FUTURE), we summarized and analyzed the epidemiological characteristics, clinical manifestations, LOS, the disease burden (in US dollars, USD) and potential risk factors for hospitalized children diagnosed with congenital toxoplasmosis, congenital rubella syndrome, congenital cytomegalovirus infection, and congenital HSV in 27 children's hospitals in China from 2015 to 2020. RESULTS: One hundred seventy-three patients aged 0-<1 year were hospitalized for congenital TORCH infections. Among infections with TORCH, hospitalization with congenital toxoplasmosis was the least common, with only five cases were reported (2.89%), while the LOS was the highest. The proportion of patients with congenital rubella syndrome (CRS) was 15.61%, and 86% of children hospitalized with CRS had cardiovascular malformations, and the economic burden was the highest. Congenital CMV infection cases accounted for the largest proportion (76.30%). Overall, 5.20% of patients were infected with HSV, and the expense of hospitalization for congenital HSV infection was relatively low. CONCLUSION: In the present study, the hospitalization proportion due to congenital TORCH infection was extremely low (17.56 per 100,000 neonates), indicating that China's congenital TORCH infection prevention and control policies remain effective. The lowest proportion of patients was hospitalized with congenital toxoplasmosis, while the LOS was the longest. The economic burden of CRS was heavy, and infants are recommended be vaccinated against RV in a timely manner. Congenital CMV infections accounted for the largest proportion of patients, suggesting that the disease burden of congenital CMV infection cannot be ignored, and the prevention of congenital CMV infection during pregnancy is still an important issue that needs to pay attention. The expense of hospitalization for congenital HSV infection was relatively low, while the disease burden increases significantly when patients develop complications. These data illustrate the importance of improving screening for congenital TORCH infections in the early diagnosis and treatment of neonatal patients.

Quality of clinical practice guidelines for gestational and congenital toxoplasmosis: A systematic review of the literature.

OBJECTIVE: To evaluate the methodological quality and transparency of the clinical practice guidelines (CPGs) for the prevention, diagnosis, and treatment of gestational and congenital toxoplasmosis (CT). METHODS: Systematic review of the literature on gestational and CT CPGs conducted in the MEDLINE, Embase, TripDatabase, Biblioteca Virtual en Salud databases and extensive manual searches in 19 CPG repositories. The characteristics of each of the guidelines were extracted using My AGREE PLUS on-line. Three reviewers assessed overall quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. RESULTS: The combined systematic review found 8651 citations. Of them 46 full texts were reviewed, and eight documents were finally included: four toxoplasmosis CPGs, three prenatal care CPGs that included recommendations on toxoplasmosis, and one pregnancy infection guideline that also included recommendations on toxoplasmosis. The AGREE II domains found to have the highest scores were 'clarity of presentation' (85%; [37%-100%]), followed by 'scope and purpose' (73%; [33%-98%]), and 'editorial independence' (51%; [3%-94%]); the domains with the lowest scores were 'rigour of development' (36%; [11%-79%]), 'stakeholder involvement' (34%; [24%-85%]), and 'applicability' (17%; [6%-83%]). The Colombian and Spanish-Agencia de Evaluación de Tecnologías Sanitarias de Andalucía (AETSA) CPGs had the highest global AGREE II scores. Absolute interrater agreement was good to excellent. CONCLUSION: Substantial quality variation was found among CPGs, which provided recommendations in accordance with the context of the disease in the corresponding country or region. Only two of the CPGs appraised obtained a good score and are classified as 'recommended'.

High performance of a novel point-of-care blood test for Toxoplasma infection in women from diverse regions of Morocco.

Point-of-care (POC) testing for Toxoplasma infection has the potential to revolutionize diagnosis and management of toxoplasmosis, especially in high-risk populations in areas with significant environmental contamination and poor health infrastructure precluding appropriate follow-up and preventing access to medical care. Toxoplasmosis is a significant public health challenge in Morocco, with a relatively heavy burden of infection and, to this point, minimal investment nationally to address this infection. Herein, we analyse the performance of a novel, low-cost rapid test using fingerstick-derived whole blood from 632 women (82 of whom were pregnant) from slums, educational centres, and from nomad groups across different geographical regions (i.e. oceanic, mountainous) of Morocco. The POC test was highly sensitive and specific from all settings. In the first group of 283 women, sera were tested by Platelia ELISA IgG and IgM along with fingerstick whole blood test. Then a matrix study with 349 women was performed in which fingerstick - POC test results and serum obtained by venipuncture contemporaneously were compared. These results show high POC test performance (Sensitivity: 96.4% [IC95 90.6-98.9%]; Specificity: 99.6% [IC95 97.3-99.9%]) and high prevalence of Toxoplasma infection among women living in rural and mountainous areas, and in urban areas with lower educational levels. The high performance of POC test confirms that it can reduce the need for venipuncture and clinical infrastructure in a low-resource setting. It can be used to efficiently perform seroprevalence determinations in large group settings across a range of demographics, and potentially expands healthcare access, thereby preventing human suffering.

Toxoplasmosis screening during pregnancy in France: Opinion of an expert panel for the CNGOF.

Prenatal screening to prevent congenital toxoplasmosis as performed in France for several decades has been questioned in view of the decreasing incidence of this infection and the cost of testing. The French College of Obstetrics and Gynecology mandated a multidisciplinary panel of experts to perform a reassessment of the screening program in accordance with international good practice. In France, about 70% of pregnant women are not immune to T. gondii, and 0.2-0.25% become infected during pregnancy. The risk of maternal-fetal transmission of infection is on average 25-29% and depends greatly on the gestational age at seroconversion. In case of fetal transmission, the outcome is livebirth in 95% of cases, with latent congenital toxoplasmosis in 90% of cases and symptomatic forms in 10% of cases, of which 1/3 are severe and 2/3 moderate. Biological techniques have satisfactory performance regarding serologies for the diagnosis of maternal infections and PCR on amniotic fluid for the prenatal diagnosis of congenital toxoplasmosis. Primary prevention of toxoplasmosis is based on hygiene measures that are relatively simple, but poorly implemented. In case of maternal seroconversion, there is a strong case for prenatal prophylactic treatment as soon as possible (ideally within 3 weeks of seroconversion), spiramycin before 14 weeks of gestation (WG), and with a tendency to superiority of the pyrimethamine/sulfadiazine association over spiramycin beyond 14 W G, in order to reduce the risk of symptomatic congenital toxoplasmosis. In case of congenital toxoplasmosis, prompt initiation of treatment reduces the occurrence of cerebral signs and symptoms, as well as retinal lesions. Several medico-economic evaluations of the French toxoplasmosis screening program have been conducted including an individual cost-effectiveness approach with decision analysis which concluded on the profitability of prenatal screening as carried out in France (monthly surveillance of seronegative women, prenatal treatment in case of seroconversion, termination of pregnancy in severe forms). Though most international societies do not recommend systematic screening for mainly financial reasons, if congenital toxoplasmosis appears benign in France today, it is probably thanks to screening and the possibility of early treatment of fetuses and/or newborns. Thus, the panel recommends continuing for now the program in France for prevention of congenital toxoplasmosis.

Ampliação do uso do teste do pezinho para a detecção da toxoplasmose congênita / Expansion of the use of the heel test to the detection of congenital toxoplasmosis

CONTEXTO: A toxoplasmose congênita (TC) é uma doença infecciosa que resulta da transferência transplacentária do Toxoplasma gondii para o concepto, decorrente de infecção primária da mãe durante a gestação. Os recém-nascidos que apresentam manifestações clínicas podem ter sinais no período neonatal ou nos primeiros meses de vida. Esses casos costumam ter, com mais frequência, sequelas graves, como acometimento visual em graus variados, sequelas neurológicas, anormalidades motoras e surdez. A prevalência de toxoplasmose é alta no Brasil, podendo variar de 64,9 % a 91,6 %, dependendo da região. Uma porcentagem alta (50-80%) das mulheres em idade fértil são IgG positivas. Entre 20-50% das mulheres em idade reprodutiva são suscetíveis (IgG e IgM negativas) e estão em risco de adquirir a infecção na gestação. Estudos realizados no Brasil mostraram que nascem entre 5-23 crianças infectadas a cada 10.000 nascidos vivos. A inclusão da toxoplasmose no teste de pezinho, complementar à triagem materna, no Brasil, foi sugerida por vários especialistas. Segundo Neto e colaboradores, embora a eficácia a longo prazo do tratamento da TC não tenha sido bem estabelecida, a disponibilidade de diagnósticos confiáveis, a logística funcional e criação de redes para triagem, a gravidade das sequelas e a prevalência muito alta da doença, fazem da triagem neonatal para TC uma alternativa a nenhuma triagem. PERGUNTA: O teste de rastreamento da toxoplasmose congênita através da pesquisa de anticorpos IgM anti-Toxoplasma gondii no sangue colhido em papel filtro é seguro, efetivo e eficiente o suficiente para modificar as condutas e os desfechos imediatos e em longo prazo nos pacientes diagnosticados? Evidências científicas: Segundo dados de estudo nacional a triagem neonatal identificou casos de infecção não detectados pela obtenção de apenas uma ou duas amostras de soro de mulheres grávidas para sorologia de T. gondii, principalmente quando a infecção foi adquirida no final da gravidez. O teste sorológico para diagnóstico da TC que apresentou maior desempenho foi o ISAGA (immunosorbent agglutination assay) com a sensibilidade variando de 54-87% e a especificidade de 77,7-100%. Não há estudos randomizados avaliando a terapia antiparasitária em lactentes e as evidências são oriundas de estudos observacionais. Comparado com os controles históricos (não tratados ou tratados por um mês), o tratamento combinado por 12 meses foi associado a melhores resultados neurológicos, cognitivos e auditivos e prevenção de novas lesões oculares. AVALIAÇÃO ECONÔMICA: Sem qualquer triagem na população, o custo por nascimento seria de R$ 11,42, ou cerca de R$ 33.555.477,36 para todos os nascimentos no Brasil no ano de 2018. A ampliação do teste de pezinho para toxoplasmose congênita, incluindo custos da triagem e do tratamento durante o primeiro ano de vida, teria um custo de R$ 8,19 por nascimento e um custo total de R$ 24.064.742,52 para todos os nascimentos. A triagem pré-natal apresentou maior custo entre as estratégias testadas, R$ 57,96 por nascimento, incluindo a triagem realizada nos três trimestres da gravidez, o tratamento da gestante e da criança. Em um ano, o custo total da triagem pré-natal seria de R$ 170.304.331,68. A realização da triagem neonatal implicaria em R$ 13.516.216,8 de custos salvos em comparação com não fazer nenhuma triagem. Considerando o desfecho sequela relacionado à TC evitada, apesar da triagem neonatal apresentar menor custo ela foi menos eficaz que a triagem pré-natal. A relação custoefetividade incremental em 1 ano foi de R$ 50,02 por sequelas da TC evitadas em comparação à triagem neonatal. A não realização de qualquer triagem foi dominada pelas triagens avaliadas. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: No primeiro cenário, considerando o custo por nascido vivo de R$ 8,19 obtido na avaliação econômica, o impacto orçamentário (IO) seria em torno de R$ 23,9 milhões. Considerando uma taxa de transmissão materno-fetal de 18,5% identificada em estudo epidemiológico brasileiro, o IO entre os cinco anos foi de aproximadamente R$ 55 milhões e considerando uma taxa de transmissão inferior de 3,5% o impacto ficaria aproximadamente R$ 54 milhões. O último cenário considerou a prevalência de toxoplasmose congênita de 6/10.000 nascidos vivos obtendo um IO seria em torno de R$ 55,44 à R$ 55,56 milhões. CONSIDERAÇÕES FINAIS: A TC é um importante problema de saúde, prevalente no Brasil (5-23 crianças infectadas a cada 10.000 nascidos vivos) e associada frequentemente a graves sequelas. A detecção de IgM no período neonatal diagnostica a toxoplasmose congênita em mais de 80% dos casos. O tratamento precoce parece reduzir os danos causados pela doença. A pesquisa de IgM anti-T. gondii para triagem neonatal já foi aplicada em diferentes regiões no Brasil e a relação custo/benefício do diagnóstico precoce é favorável na ausência de triagem pré-natal bem executada. RECOMENDAÇÕES PRELIMINAR DA CONITEC: A Conitec, em sua 84ª reunião ordinária, no dia 04 de dezembro de 2019, recomendou que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à ampliação no SUS do teste de pezinho para detecção da toxoplasmose congênita. Foi considerado que a toxoplasmose congênita é um problema de saúde pública e que o diagnóstico e tratamento precoce possuem potencial para redução das sequelas da doença em crianças. CONSULTA PÚBLICA: O Relatório de Recomendação da Conitec foi disponibilizado por meio da Consulta Pública nº 84/2019 entre os dias 02/01/2020 e 21/01/2020. Foram recebidas 244 contribuições, sendo 110 técnico-científicas e 134 contribuições de experiência ou opinião. Após apreciação das contribuições encaminhadas pela Consulta Pública, o plenário da Conitec entendeu que não houve argumentação suficiente para alterar a recomendação preliminar. RECOMENDAÇÃO FINAL: Os membros da Conitec presentes na 85ª reunião ordinária, no dia 05 de fevereiro de 2020, deliberaram, por unanimidade, por recomendar a ampliação do uso do teste do pezinho para a detecção da toxoplasmose congênita. Foi assinado o Registro de Deliberação nº 507/2020. DECISÃO: Ampliar o uso do teste do pezinho para a detecção da toxoplasmose congênita, no âmbito do Sistema Único de Saúde - SUS, conforme a Portaria nº 5, publicada no Diário Oficial da União nº 44, seção 1, página 130, em 5 de março de 2020.

The cost-effectiveness of neonatal versus prenatal screening for congenital toxoplasmosis.

BACKGROUND: Congenital Toxoplasmosis (CT) can have severe consequences. France, Austria, and Slovenia have prenatal screening programs whereas some other countries are considering universal screening to reduce congenital transmission and severity of infection in children. The efficiency of such programs is debated increasingly as seroprevalence among pregnant women and incidence of congenital toxoplasmosis show a steady decrease. In addition, uncertainty remains regarding the effectiveness of pre- and postnatal treatments. METHOD: To identify cost-effective strategies, prenatal and neonatal screenings were compared using a decision-analytic model based on French guidelines and current knowledge of long-term evolution of the disease in treated children. Epidemiological data were extracted from the scientific literature and clinical data from the French Lyon cohort. Strategies were compared at one year of age, when infection can be definitively evaluated, and at 15 years of age, after which validated outcome data become scarce. The analysis was performed from the French Health Insurance System perspective and included direct medical costs for pregnant women and their children. RESULTS: The 1-year Incremental Cost-Effectiveness Ratio showed that prenatal screening would require investing €14,826 to avoid one adverse event (liveborn with CT, fetal loss, neonatal death or pregnancy termination) compared to neonatal screening. Extra investment increased up to €21,472 when considering the 15-year endpoint. CONCLUSIONS: Prenatal screening is cost-effective as compared to neonatal screening in moderate prevalence areas with predominant Type II strains. In addition, prenatal screening, by providing closer follow-up of women at risk increases the number of occasions for education avoiding toxoplasmosis.

[Serological monitoring and prevention of toxoplasmosis during pregnancy]. / Surveillance sérologique et prévention de la toxoplasmose chez la femme enceinte.

Serological monitoring and prevention of toxoplasmosis during pregnancy. Determination of the serological status against toxoplasmosis is mandatory in France during pregnancy. Recently, the national social welfare system decided to include new exams (IgG avidity and western-blot) useful to assess the serological status and to date the infection with a better accuracy. The role of the attending doctor is essential, particularly at the beginning of pregnancy and after delivery. We summarize here key points which must be known by a general practitioner to understand serological results and take care of his patients.

Surveillance sérologique et prévention de la toxoplasmose chez la femme enceinte. Le dépistage systématique de la toxoplasmose chez la femme enceinte est une obligation légale en France. Le code de nomenclature des actes de biologie médicale a intégré en 2019 de nouveaux examens (western-blot IgG et mesure de l'indice d'avidité des IgG) permettant d'établir le statut sérologique ou de dater l'infection avec une meilleure spécificité. La place du médecin traitant est essentielle dans la prise en charge de la grossesse, en particulier au moment de la déclaration et pour le suivi post-partum. Nous rappelons ici les éléments biologiques essentiels que tout praticien doit connaître et les éléments de la prise en charge à organiser en fonction des résultats sérologiques.

Congenital toxoplasmosis in Austria: Prenatal screening for prevention is cost-saving.

BACKGROUND: Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone. Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years. CONCLUSIONS/SIGNIFICANCE: Cost savings under a national program of prenatal screening for toxoplasma infection and treatment are outstanding. Our results are of relevance for health care providers by supplying economic data based on a unique national dataset including long-term follow-up of affected infants.

Public Health Impact of Congenital Toxoplasmosis and Cytomegalovirus Infection in Belgium, 2013: A Systematic Review and Data Synthesis.

Congenital toxoplasmosis (CT) and cytomegalovirus infection (cCMV) may cause significant morbidity and even fetal or neonatal mortality. We aimed to quantify the disease burden of CT and cCMV in Belgium in terms of disability-adjusted life years (DALYs) and identify data gaps. The public health impact of CT and cCMV in Belgium in 2013 was 188 (95% uncertainty interval [UI], 43-419) and 1976 (95% UI, 757-4067) DALYs, respectively. The major data gaps identified were representative Belgian studies; information on important sequelae, intrauterine mortality, and termination of pregnancy; and late onset sequelae. A scenario analysis showed important increases in years of life lost when the burden due to fetal losses was included and decreases in DALYs when comprehensive CT prevention measures were conducted. Addressing the key data gaps identified may allow generation of the data needed to break the vicious circle of underrecognition.

Towards Universal Screening for Toxoplasmosis: Rapid, Cost-Effective, and Simultaneous Detection of Anti-Toxoplasma IgG, IgM, and IgA Antibodies by Use of Very Small Serum Volumes.

Rapid, cost-effective, and early determination of the serological status of potentially infected individuals, particularly pregnant women, can be critical in preventing life-threatening infections and subsequent fetal congenital abnormalities. An article in this issue of the Journal of Clinical Microbiology (X. Li, C. Pomares, G. Gonfrier, B. Koh, S. Zhu, M. Gong, J. G. Montoya, and H. Dai, J Clin Microbiol 54:1726-1733, 2016, http://dx.doi.org/10.1128/JCM.03371-15) describes an innovative multiplexed immunoassay that offers a path toward universal screening.

Treatment of Congenital Toxoplasmosis: Safety of the Sulfadoxine-Pyrimethamine Combination in Children Based on a Method of Causality Assessment.

BACKGROUND: The treatment of newborns and infants with congenital toxoplasmosis is standard practice. Some observational studies have examined safety in newborns, but most of these failed to provide sufficient details for a provisional assessment of causality. The aim of this study was to evaluate the clinical and biological adverse effects of the combination of sulfadoxine-pyrimethamine. METHODS: Sixty-five children treated for 1 year with a combination of sulfadoxine-pyrimethamine (1 dose every 10 days) for congenital toxoplasmosis were followed up to evaluate abnormal hematological values and potential adverse events using a standardized method of causality assessment. RESULTS: Nine patients (13.8%) presented at least 1 adverse clinical event that was nonspecific, such as diarrhea on the day of drug administration, vomiting and agitation. In 1 patient, erythema appeared at the end of the treatment and resolved within 10 days. None of these events was attributed to the treatment. Six patients (9.2%) developed an adverse hematological event (neutropenia, n = 3; eosinophilia, n = 2 and both anemia and eosinophilia, n = 1) that was considered to be possibly related to the sulfadoxine-pyrimethamine combination. Four treatments were temporarily interrupted, and toxicity was observed after readministration of treatment in 1 case only. However, none of these adverse events was life threatening. CONCLUSIONS: According to our results and previously published data, the combination of sulfadoxine-pyrimethamine seems to be well tolerated. However, the sample size of our study was too small to rule out the risk of less frequent, but nevertheless severe, reactions and, in particular, of hypersensitivity reactions.

Ocorrência de toxoplasmose congênita, avaliação do conhecimento sobre toxoplasmose e do acompanhamento sorológico das gestantes e implantação de medidas de prevenção primária nos programas de prénatal da rede pública de saúde do município de Niterói-RJ / Occurrence of congenital toxoplasmosis, evaluation of toxoplasmosis-related knowledge and serological monitoring of pregnant women and implementation of primary prevention measures in pre-natal programs of public health in the city of Niterói-RJ

INTRODUÇÃO: Toxoplasma gondii pode ocasionar infecção fetal por via transplacentária, sendo a toxoplasmose congênita um grave problema de saúde pública. É fundamental no pré-natal o diagnóstico laboratorial precoce, bem como a transmissão de informações sobre a doença. OBJETIVOS: Avaliar o conhecimento sobre a toxoplasmose entre as gestantes e os profissionais de saúde e contribuir para a implantação da prevenção primária da toxoplasmose congênita nos Programas de pré-natal do município de Niterói-RJ. Metodologia: Participaram da pesquisa 500 gestantes e 141 profissionais de saúde provenientes de 17 módulos do Programa Médico de Família e de duas Policlínicas de Niterói-RJ, de 2013 a 2016. Todos assinaram o TCLE e responderam um questionário. Após esta etapa foram realizadas ações de educação e saúde, utilizando palestras, materiais educativos e um modelo educativo interativo. Após três meses, 145 gestantes responderam os questionários novamente. RESULTADOS: Das 500 gestantes, 226 (45,2%) conheciam a toxoplasmose. Destas, 23,5% tiveram informações por amigos e 19,0% pelo médico. Do total de gestantes, 6,8% relataram contato com fezes de gatos, 14,0% contato com o solo sem luvas, 10,4% consumiam verduras, legumes e frutas cruas sem higiene adequada, 9,6% carne crua e 23,4% carne mal passada, 17,8% consumiam embutidos mal cozidos, 10,6% bebiam leite não pasteurizado e 24,0% água de abastecimento público sem filtrar. Ao comparar os questionários de 145 gestantes pré e pós atividades educativas, o contato com o solo sem uso de luvas teve redução significativa estatisticamente, de 11,0% para 4,8% (p=0,022) e o consumo de água sem filtro reduziu de 26,9% para 20,0% (p=0,000), consumo de carne crua reduziu para 6,9% e de carne mal cozida para 17,9%. Foram mais citados como medidas profiláticas: lavagem dos alimentos (62,1%), lavagem das mãos (62,1%) e consumo de carne cozida (61,4%)...

INTRODUCTION: toxoplasma gondii can cause fetal infection by transplacental route and congenital toxoplasmosis is a serious public health problem. It is fundamental in prenatal early laboratory diagnostics, as well as the transmission of information about the disease. OBJECTIVES: to evaluate the knowledge of toxoplasmosis among pregnant women and health professionals and to contribute to the congenital toxoplasmosis primary prevention implementation in prenatal programs in the city of Niterói, RJ. METHODS: Participated in the study 500 pregnant women and 141 health professionals from 17 modules of the Family Doctor Program and two polyclinics in Niterói-RJ from 2013 to 2016. All signed the consent form and answered a questionnaire. After this stage, health education actions were conducted, usinglectures, educational materials and interactive educational model. After three months,145 pregnant women answered the questionnaires again. RESULTS: Among 500pregnant women, 226 (45.2%) knew toxoplasmosis. 23.5% had information from friends and 19.0% by the doctor. Of the total of pregnant women, 6.8% reported contact with cat feces, 14.0% contact with the ground without gloves, 10.4%consumed vegetables and raw fruits without proper hygiene, 9.6% raw meat and23.4% undercooked meat, 17.8% consumed embedded meat, 10.6% drank raw milk and 24.0% water from public supply system without filtering. By comparing the questionnaires of 145 pregnant women pre and post educational activities, contact with the ground without gloves had statistically significant reduction of 11.0% to 4.8%(p = 0.022) and unfiltered water consumption reduced of 26.9% to 20.0% (p = 0.000),consumption of raw meat reduced to 6.9% and undercooked meat to 17.9%. Theprophylactic measures most frequently cited were: washing food (62.1%), handwashing (62.1%) and consumption of cooked meat (61.4%)...

Data-driven methods for imputing national-level incidence in global burden of disease studies.

OBJECTIVE: To develop transparent and reproducible methods for imputing missing data on disease incidence at national-level for the year 2005. METHODS: We compared several models for imputing missing country-level incidence rates for two foodborne diseases - congenital toxoplasmosis and aflatoxin-related hepatocellular carcinoma. Missing values were assumed to be missing at random. Predictor variables were selected using least absolute shrinkage and selection operator regression. We compared the predictive performance of naive extrapolation approaches and Bayesian random and mixed-effects regression models. Leave-one-out cross-validation was used to evaluate model accuracy. FINDINGS: The predictive accuracy of the Bayesian mixed-effects models was significantly better than that of the naive extrapolation method for one of the two disease models. However, Bayesian mixed-effects models produced wider prediction intervals for both data sets. CONCLUSION: Several approaches are available for imputing missing data at national level. Strengths of a hierarchical regression approach for this type of task are the ability to derive estimates from other similar countries, transparency, computational efficiency and ease of interpretation. The inclusion of informative covariates may improve model performance, but results should be appraised carefully.

Assessment of the IgA immunosorbent agglutination assay for the diagnosis of congenital toxoplasmosis on a series of 145 toxoplasmic seroconversions.

A retrospective analysis of 145 medical records from our teaching hospital laboratory showed an overall specificity of greater than 97% for the IgA immunosorbent agglutination assay (ISAGA A) performed on the sera of babies to diagnose congenital toxoplasmosis (CT). These actualized data emphasize the ability of this test to confirm a diagnosis of congenital toxoplasmosis.

Multicentric comparative assessment of the bio-evolution Toxoplasma gondii detection kit with eight laboratory-developed PCR assays for molecular diagnosis of congenital toxoplasmosis.

The detection of Toxoplasma gondii in amniotic fluid is an essential tool for the prenatal diagnosis of congenital toxoplasmosis and is currently essentially based on the use of PCR. Although some consensus is emerging, this molecular diagnosis suffers from a lack of standardization and an extreme diversity of laboratory-developed methods. Commercial kits for the detection of T. gondii by PCR were recently developed and offer certain advantages; however, they must be assessed in comparison with optimized reference PCR assays. The present multicentric study aimed to compare the performances of the Bio-Evolution T. gondii detection kit and laboratory-developed PCR assays set up in eight proficient centers in France. The study compared 157 amniotic fluid samples and found concordances of 99% and 100% using 76 T. gondii-infected samples and 81 uninfected samples, respectively. Moreover, taking into account the classification of the European Research Network on Congenital Toxoplasmosis, the overall diagnostic sensitivity of all assays was identical and calculated to be 86% (54/63); specificity was 100% for all assays. Finally, the relative quantification results were in good agreement between the kit and the laboratory-developed assays. The good performances of this commercial kit are probably in part linked to the use of a number of good practices: detection in multiplicate, amplification of the repetitive DNA target rep529, and the use of an internal control for the detection of PCR inhibitors. The only drawbacks noted at the time of the study were the absence of uracil-N-glycosylase and small defects in the reliability of the production of different reagents.

Assessment of laboratory methods used in the diagnosis of congenital toxoplasmosis after maternal treatment with spiramycin in pregnancy.

BACKGROUND: The different laboratory methods used in the diagnosis of congenital toxoplasmosis have variable sensitivity and specificity. There is no evidence to prove that maternal treatment reduces the risk of fetal infection. The purpose of this study was to assess methods for the confirmation of congenital toxoplasmosis after maternal treatment with spiramycin during pregnancy, and to evaluate the effect of this treatment on clinical manifestations of the disease in newborns (NB). METHODS: This was a community-based, cross-sectional study of acute toxoplasmosis in newborns at risk of acquiring congenital infection. Participating newborns were born in the Clinical Hospital Maternity Ward of the Federal University of Goiás. Eligible participants were divided into 2 groups: group 1 consisted of 44 newborns born to mothers treated with spiramycin during pregnancy and group 2 consisted of 24 newborns born to mothers not treated with spiramycin during pregnancy because the diagnosis of toxoplasmosis was not performed. The sensitivity and specifity of PCR for T. gondii DNA in peripheral blood and serological testing for specific anti-T. gondii IgM and IgA, and the effects of maternal spiramycin treatment on these parameters, were determined by associating test results with clinical manifestations of disease. RESULTS: The sensitivity of the markers (T. gondii DNA detected by PCR, and the presence of specific anti-T. gondii IgM and IgA) for congenital toxoplasmosis was higher in group 2 than in group 1 (31.6, 68.4, 36.8% and 3.7, 25.9, 11.1% respectively). Even with a low PCR sensitivity, the group 2 results indicate the importance of developing new techniques for the diagnosis of congenital toxoplasmosis in newborns. Within group 1, 70.4% of the infected newborns were asymptomatic and, in group 2, 68.4% showed clinical manifestations of congenital toxoplasmosis. CONCLUSIONS: The higher proportion of infants without clinical symptoms in group 1 (70.4%) suggests the maternal treatment with spiramycin delays fetal infection, reducing the clinical sequelae of the disease in newborns. Given the low sensitivity of the tests used, when there is suspicion of congenital transmission several serological and parasitological tests are required in order to confirm or exclude congenital toxoplasmosis in newborns.