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.

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.

Toxoplasmose na gestação: estudo clínico, diagnóstico e epidemiológico em um centro de referência do Rio de Janeiro / Toxoplasmosis in pregnancy: clinical, diagnostic and epidemiological study in a reference center in Rio de Janeiro

A toxoplasmose é uma zoonose de distribuição mundial, altamente prevalente no Brasil. A infecção em gestantes incorre no risco de acometimento fetal. O rastreamento sorológico durante o pré-natal é importante visto que o curso da doença é em sua maioria subclínico. O tratamento compreende o uso de espiramicina, e em caso de confirmação de infecção fetal, sulfadiazina, pirimetamina e ácido folínico. A reação em cadeia da polimerase (PCR) no líquido amniótico apresenta excelente sensibilidade e especificidade e permite estabelecer o diagnóstico fetal. Fatores sociais já foram relacionados à infecção congênita pois influenciam diretamente na qualidade da assistência pré-natal. Ainda não há um consenso nacional para a condução da toxoplasmose na gestação. O objetivo deste estudo é descrever os dados clínicos, laboratoriais e epidemiológicos de gestantes e seus recém-nascidos acompanhados em um centro de referência no Rio de Janeiro com diagnóstico de toxoplasmose. Este é um estudo descritivo de uma coorte de gestantes com toxoplasmose acompanhadas no período de maio de 2014 a dezembro de 2017. A amostra foi composta por 334 participantes. Foi realizada entrevista presencial, por telefone e revisão de prontuários, com coleta de dados sociodemográficos. Foram abordadas questões referentes ao conhecimento sobre a doença e suas formas de prevenção, além de dados clínicos e laboratoriais das gestantes e dos recém-nascidos. Observamos predomínio de uma população de baixa renda e pouca escolaridade, proveniente principalmente dos serviços públicos de saúde (178/53,29%) e encaminhadas ao centro de referência tardiamente, no segundo e terceiro trimestre de gestação (286/85,63%). O diagnóstico de toxoplasmose aguda não foi confirmado em 171 (51,20%) casos e o tratamento foi iniciado nos serviços de origem em apenas 183 (54,95%) gestantes, com prescrição incorreta em 45 (24,59%) destas. Foram realizadas 72 amniocenteses, com positividade da reação em cadeia da polimerase em tempo real (qPCR) no líquido amniótico em dois (2,78%) casos. O diagnóstico de toxoplasmose congênita ao nascimento foi identificado em oito (5,44%) recém-nascidos. O diagnóstico e o tratamento tardios da toxoplasmose na gestação foram fatores preponderantes como oportunidades perdidas na prevenção da doença congênita.

Toxoplasmosis is a zoonotic disease that occurs all over the world and is highly prevalent in Brazil. During pregnancy, it may affect the fetus. Serological screening during prenatal care is important because the course of the disease is mostly asymptomatic. Treatment includes the use of spiramycin, and, should fetal infection be confirmed, sulfadiazine, pyrimethamine and folinic acid. Polymerase chain reaction (PCR) in amniotic fluid shows excellent sensitivity and specificity and enables fetal diagnosis. Social factors have been linked to congenital infection because they have a direct impact on the quality of prenatal care. There is no national consensus for toxoplasmosis treatment during pregnancy. The objective of this study is to describe the clinical, laboratory and epidemiological data of pregnant women and their newborns with a diagnosis of toxoplasmosis treated at a referral center in Rio de Janeiro. This is a descriptive study of a cohort of pregnant women with toxoplasmosis accompanied form May 2014 to December 2017. The sample was composed of 334 participants. Face-to-face interviews and by telephone were conducted, as well as the analysis of medical records to collect sociodemographic data. Questions regarding knowledge about the disease and its types of prevention, as well as clinical and laboratory data of pregnant women and newborns were addressed. We observed a predominance of low-income population with little schooling, mainly from public health services (178/53,29%) and referred to the treatment center late in the second and third trimester of pregnancy (286/85,63%). The diagnosis of acute toxoplasmosis was not confirmed in 171 (51.20%) cases and only 183 (54,95%) pregnant women started their treatment at the first clinic they went to, with an incorrect prescription in 45 (24,59%) of these cases. A total of 72 amniocenteses were performed, with two (2,78%) positive real-time polymerase chain reaction (qPCR) in the amniotic fluid. Congenital toxoplasmosis at birth was identified in eight (5,44%) newborns. Late diagnosis and treatment of toxoplasmosis during pregnancy resulted in several missed opportunities to prevent congenital disease.

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.

Comparative assessment of a commercial kit and two laboratory-developed PCR assays for molecular diagnosis of congenital toxoplasmosis.

Toxoplasmosis is a worldwide infection that may cause severe disease and is regarded as a serious health problem in France. Detection of the parasite by molecular methods is crucial for diagnosing the disease. The extreme diversity of methods and performances of Toxoplasma PCR assays makes the use of commercial PCR kits an attractive alternative, as they offer a chance for standardization. We compared the performances of three molecular methods for the detection of Toxoplasma gondii DNA in amniotic fluid: a commercial method using nested PCR and two laboratory-developed methods, one using conventional PCR and the other one real-time PCR. This evaluation was based upon a T. gondii DNA serial dilution assay, three amniotic fluid samples spiked with T. gondii at different concentrations, and a clinical cohort of 33 amniotic fluid samples. The T. gondii DNA serial dilution assay showed a much lower sensitivity for the commercial kit than for the laboratory-developed methods. Moreover, out of 12 proven congenital toxoplasmosis cases, 91.7% were detected by the laboratory-developed assays, whereas only 50% were detected by the commercial kit. A lack of sensitivity of the method, partly due to the presence of PCR inhibitors, was the main drawback of the commercial method. This study emphasizes that commercial PCR diagnostic kits do not systematically perform better than carefully optimized laboratory-developed methods. There is a need for thorough evaluation of such kits by proficient groups, as well as for performance standards that commercial kits can be tested against to improve confidence in those selected by health care providers.

Congenital toxoplasmosis: evaluation of molecular and serological methods for achieving economic and early diagnosis among Egyptian preterm infants.

BACKGROUND: Early diagnosis of congenital toxoplasmosis (CT) is difficult when specific immunoglobulin M (IgM) antibodies are absent, or if persist for months, in the newborn infant's blood. OBJECTIVES: To study the risk factors of neonatal toxoplasmosis and to compare different immunologic profiles (Toxoplasma-specific IgM, IgA antibodies and the avidity of IgG antibodies) with polymerase chain reaction (PCR) for reaching economic and early postnatal diagnosis. MATERIALS AND METHODS: We prospectively studied 80 preterm neonates, recruited from neonatal intensive care units (NICUs) of Cairo University hospitals. Whose gestational age ≤ 34 weeks with (n = 60) or without (n = 20) CT risk. Serum samples for specific IgA, IgM antibodies and avidity of IgG toxoplasma antibodies were measured by ELISA then compared to PCR. RESULTS: Of the 60 studied cases, 16 (26.7%) were positive for toxoplasmosis by PCR, of which 15 (25%) had low avidity of IgG antibodies (positive), 14 (23.3%) were positive for IgA and 10 (16.7%) were positive for IgM, with sensitivity for avidity of IgG, IgA and IgM: 93.2%, 87.5% and 62.5%, respectively. CONCLUSION: Determination of avidity of IgG toxoplasma antibodies and/or serological detection of specific IgA for toxoplasmosis offer, simple tests for diagnosis of congenital toxoplasmosis with (better sensitivity) than IgM.

Risk factors for Toxoplasma gondii infection in the United States.

BACKGROUND: Toxoplasmosis can cause severe ocular and neurological disease. We sought to determine risk factors for Toxoplasma gondii infection in the United States. METHODS: We conducted a case-control study of adults recently infected with T. gondii. Case patients were selected from the Palo Alto Medical Foundation Toxoplasma Serology Laboratory from August 2002 through May 2007; control patients were randomly selected from among T. gondii-seronegative persons. Data were obtained from serological testing and patient questionnaires. RESULTS: We evaluated 148 case patients with recent T. gondii infection and 413 control patients. In multivariate analysis, an elevated risk of recent T. gondii infection was associated with the following factors: eating raw ground beef (adjusted odds ratio [aOR], 6.67; 95% confidence limits [CLs], 2.09, 21.24; attributable risk [AR], 7%); eating rare lamb (aOR, 8.39; 95% CLs, 3.68, 19.16; AR, 20%); eating locally produced cured, dried, or smoked meat (aOR, 1.97; 95% CLs, 1.18, 3.28; AR, 22%); working with meat (aOR, 3.15; 95% CLs, 1.09, 9.10; AR, 5%); drinking unpasteurized goat's milk (aOR, 5.09; 95% CLs, 1.45, 17.80; AR, 4%); and having 3 or more kittens (aOR, 27.89; 95% CLs, 5.72, 135.86; AR, 10%). Eating raw oysters, clams, or mussels (aOR, 2.22; 95% CLs, 1.07, 4.61; AR, 16%) was significant in a separate model among persons asked this question. Subgroup results are also provided for women and for pregnant women. CONCLUSIONS: In the United States, exposure to certain raw or undercooked foods and exposure to kittens are risk factors for T. gondii infection. Knowledge of these risk factors will help to target prevention efforts.

Congenital toxoplasmosis and DALYs in the Netherlands.

The calculation of disability-adjusted life years (DALYs) enables public health policy makers to compare the burden of disease of a specific disease with that of other (infectious) diseases. The incidence of a disease is important for the calculation of DALYs. To estimate the incidence of congenital toxoplasmosis (CT), a random sample of 10,008 dried blood spot filter paper cards from babies born in 2006 in the Netherlands were tested for Toxoplasma gondii-specific IgM antibodies. Eighteen samples were confirmed as positive for IgM, resulting in an observed birth incidence of CT of 1.8 cases per 1,000 live-born children in 2006 and an adjusted incidence of 2.0 cases per 1,000. This means that 388 infected children were born in 2006. The most likely burden of disease is estimated to be 2,300 DALYs (range 820-6,710 DALYs). In the previous calculations, using data from a regional study from 1987, this estimate was 620 DALYs (range 220-1,900 DALYs). The incidence of CT in the Netherlands is much higher than previously reported; it is 10 times higher than in Denmark and 20 times higher than in Ireland, based on estimates obtained using the same methods. There is no screening program in the Netherlands; most children will be born asymptomatic and therefore will not be detected or treated.

Congenital toxoplasmosis and DALYs in the Netherlands

The calculation of disability-adjusted life years (DALYs) enables public health policy makers to compare the burden of disease of a specific disease with that of other (infectious) diseases. The incidence of a disease is important for the calculation of DALYs. To estimate the incidence of congenital toxoplasmosis (CT), a random sample of 10,008 dried blood spot filter paper cards from babies born in 2006 in the Netherlands were tested for Toxoplasma gondii-specific IgM antibodies. Eighteen samples were confirmed as positive for IgM, resulting in an observed birth incidence of CT of 1.8 cases per 1,000 live-born children in 2006 and an adjusted incidence of 2.0 cases per 1,000. This means that 388 infected children were born in 2006. The most likely burden of disease is estimated to be 2,300 DALYs (range 820-6,710 DALYs). In the previous calculations, using data from a regional study from 1987, this estimate was 620 DALYs (range 220-1,900 DALYs). The incidence of CT in the Netherlands is much higher than previously reported; it is 10 times higher than in Denmark and 20 times higher than in Ireland, based on estimates obtained using the same methods. There is no screening program in the Netherlands; most children will be born asymptomatic and therefore will not be detected or treated.

Congenital toxoplasmosis: late pregnancy infections detected by neonatal screening and maternal serological testing at delivery.

The first aim of this study was to determine the prevalence of congenital toxoplasmosis in newborn infants treated by the public health system in Porto Alegre, a city in southern Brazil, using neonatal screening for Toxoplasma gondii-specific IgM. The second aim was to investigate whether the cases detected by this approach could have been identified by the prenatal screening for antibodies to T. gondii that was performed in the same population. A fluorometric assay was used to analyse T. gondii-specific IgM in filter paper specimens obtained from newborn infants for routine screening for metabolic diseases. When the specific IgM was positive, serum samples from the infant and the mother were requested for confirmatory serological testing, and the infant underwent clinical examination. Among 10 000 infants screened for T. gondii-specific IgM, seven filter paper samples were positive, and congenital toxoplasmosis was confirmed in six patients. The prevalence of IgM specific for T. gondii was 6/10 000 [95% CI 2/10 000, 13/10 000]. One infected infant had already been identified in the maternity ward before birth, three had been identified by maternal serology at delivery, and two infants with congenital toxoplasmosis were identified solely through neonatal screening. Although four mothers of the patients with congenital toxoplasmosis received prenatal care, and three mothers had one or two serological tests for T. gondii-specific antibodies (one at first trimester, one at first and second trimesters, and the other at second and third trimesters), they were not identified during pregnancy as infected. Neonatal screening identified cases of infection not detected by obtaining only one or two serum samples from pregnant women for T. gondii serology, mainly when infection was acquired and transmitted in late pregnancy. Maternal serology at delivery and neonatal screening were especially useful in the identification of infants with congenital toxoplasmosis when the mother did not receive regular prenatal serological testing or prenatal care.

Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients' data.

BACKGROUND: Despite three decades of prenatal screening for congenital toxoplasmosis in some European countries, uncertainty remains about the effectiveness of prenatal treatment. METHODS: We did a systematic review of cohort studies based on universal screening for congenital toxoplasmosis. We did a meta-analysis using individual patients' data to assess the effect of timing and type of prenatal treatment on mother-to-child transmission of infection and clinical manifestations before age 1 year. Analyses were adjusted for gestational age at maternal seroconversion and other covariates. FINDINGS: We included 26 cohorts in the review. In 1438 treated mothers identified by prenatal screening, we found weak evidence that treatment started within 3 weeks of seroconversion reduced mother-to-child transmission compared with treatment started after 8 or more weeks (adjusted odds ratio [OR] 0.48, 95% CI 0.28-0.80; p=0.05). In 550 infected liveborn infants identified by prenatal or neonatal screening, we found no evidence that prenatal treatment significantly reduced the risk of clinical manifestations (adjusted OR for treated vs not treated 1.11, 95% CI 0.61-2.02). Increasing gestational age at seroconversion was strongly associated with increased risk of mother-to-child transmission (OR 1.15, 95% CI 1.12-1.17) and decreased risk of intracranial lesions (0.91, 0.87-0.95), but not with eye lesions (0.97, 0.93-1.00). INTERPRETATION: We found weak evidence for an association between early treatment and reduced risk of congenital toxoplasmosis. Further evidence from observational studies is unlikely to change these results and would not distinguish whether the association is due to treatment or to biases caused by confounding. Only a large randomised controlled clinical trial would provide clinicians and patients with valid evidence of the potential benefit of prenatal treatment.