Leaf hydroalcoholic extract and oleoresin from Copaifera multijuga control Toxoplasma gondii infection in human trophoblast cells and placental explants from third-trimester pregnancy.

The conventional treatment of congenital toxoplasmosis is mainly based on the combination of sulfadiazine and pyrimethamine. However, therapy with these drugs is associated with severe side effects and resistance, requiring the study of new therapeutic strategies. There are currently many studies with natural products, including Copaifera oleoresin, showing actions against some pathogens, as Trypanosoma cruzi and Leishmania. In the present study, we investigated the effects of the leaf hydroalcoholic extract and oleoresin from Copaifera multijuga against Toxoplasma gondii in human villous (BeWo) and extravillous (HTR8/SVneo) trophoblast cells, as well as in human villous explants from third-trimester pregnancy. For this purpose, both cells and villous explants were infected or not with T. gondii, treated with hydroalcoholic extract or oleoresin from C. multijuga and analyzed for toxicity, parasite proliferation, cytokine and ROS production. In parallel, both cells were infected by tachyzoites pretreated with hydroalcoholic extract or oleoresin, and adhesion, invasion and replication of the parasite were observed. Our results showed that the extract and oleoresin did not trigger toxicity in small concentrations and were able to reduce the T. gondii intracellular proliferation in cells previously infected. Also, the hydroalcoholic extract and oleoresin demonstrated an irreversible antiparasitic action in BeWo and HTR8/SVneo cells. Next, adhesion, invasion and replication of T. gondii were dampened when BeWo or HTR8/SVneo cells were infected with pretreated tachyzoites. Finally, infected and treated BeWo cells upregulated IL-6 and downmodulated IL-8, while HTR8/SVneo cells did not change significantly these cytokines when infected and treated. Finally, both the extract and oleoresin reduced the T. gondii proliferation in human explants, and no significant changes were observed in relation to cytokine production. Thus, compounds from C. multijuga presented different antiparasitic activities that were dependent on the experimental model, being the direct action on tachyzoites a common mechanism operating in both cells and villi. Considering all these parameters, the hydroalcoholic extract and oleoresin from C. multijuga can be a target for the establishment of new therapeutic strategy for congenital toxoplasmosis.

Adjunctive bradyzoite-directed therapy for reducing complications of congenital toxoplasmosis.

Congenital toxoplasmosis is caused by in utero infection of the fetus with the intracellular parasite Toxoplasma gondii. Upon infection, the parasite forms life-long cysts in fetal brain and eyes which are resistant to the currently accepted therapy of pyrimethamine and sulfadiazine. These cysts commonly reactivate later in life causing chorioretinitis and visual impairment, and rarely cause neurological complications. I hypothesize that adjunctive, bradyzoite-directed therapies have the potential to alleviate a significant burden of disease by reducing cyst burden in neonatal brain and eyes. Atovaquone is perhaps the most promising drug for further evaluation given its low side-effect profile, established safety, and efficacy in animal models reducing cyst burden. Very limited observational data in humans suggests atovaquone may prevent Toxoplasma-associated chorioretinitis recurrence. Clinical trials are needed to evaluate it and other potential drugs as adjunctive treatment in congenital toxoplasmosis.

Evaluation of colostrum as an alternative biological sample for the diagnosis of human congenital toxoplasmosis.

BACKGROUND: Toxoplasmosis is a zoonosis caused by Toxoplasma gondii, an intracellular protozoan parasite able to infect a wide range of hosts, including humans. Congenital infection can cause severe damage to the fetus. Thus, it is important to detect antibodies against the parasite to confirm clinical manifestations. Considering that all immunoglobulin isotypes may be present in biological samples from newborns and their mothers, this study aimed to evaluate the ability to diagnose recent toxoplasmosis by using colostrum, as an alternative noninvasive way to obtain biological samples, as well as to determine correlation rates between antibodies from serum samples to detect IgG, IgM and IgA isotypes against T. gondii. METHODS: A total of 289 puerperal women from Clinical Hospital of Federal University of Uberlândia (mean age: 24.8 years, range: 14 - 43 years) took part in this study. Serum and colostrum samples from these patients were analyzed using ELISA and immunoblotting assays for soluble antigens from T. gondii. RESULTS: ELISA immunoassays with serum samples showed reactivity in 47.0, 6.9 and 2.8 % of samples to anti-T. gondii IgG, IgM and IgA, respectively, in comparison with colostrum samples, which showed reactivity in 46.0, 7.9 and 2.8 % of samples to the same isotypes. Also, significant correlation rates of anti-T. gondii antibody levels between serum and colostrum samples were observed. Interestingly, reactivity to IgM and/or IgA in colostrum and/or serum confirmed clinical manifestations of congenital toxoplasmosis in three newborns. Immunoblotting assays showed that it is possible to detect IgG, IgM and IgA antibodies against various antigens of T. gondii in serum and colostrum samples. IgG antibodies in serum and colostrum samples recognized more antigenic fractions than IgM and IgA antibodies. Serum IgG detected more antigenic fractions than IgG antibodies present in the colostrum of the same patient. In contrast, specific IgA present in colostrum recognized a higher number of antigens than IgA present in serum samples of the same patient. CONCLUSIONS: Overall, the results show that it is important to investigate the occurrence of congenital toxoplasmosis, even at puerperal period. Furthermore, this study demonstrates that T. gondii-specific IgG, IgM and IgA antibodies in serum and colostrum samples from puerperal women may be detected with a significant correlation, suggesting that colostrum may also be used as an alternative biological sample to efficiently diagnose recent human toxoplasmosis.

Goats reinfected with toxoplasma gondii: loss of viable prolificacy and gross revenue / Cabras reinfectadas com toxoplasma gondii: perdas de prolificidade viável e receita bruta

We determined the reproductive parameters and clinical disorders in pregnant goats infected and reinfected with Toxoplasma gondii, and posteriorly the loss of gross revenue due to congenital toxoplasmosis was estimated. Of the 25 non-pregnant females negative for T. gondii, 20 were orally inoculated (ME 49 strain) and of these, 15 pregnant females chronically infected were orally reinoculated (VEG strain) with T. gondii oocysts. Five groups were formed (n=5): GI, GII and GIII (reinoculations at 40, 80 and 120 days of gestation, respectively), GIV (inoculation) and GV (no inoculation). Clinical and serological exams were performed on days 0 (prior to inoculation), 3, 6 9, 15 and 21 and every 7 days post-inoculation. Exams were also performed on day 3 and every 7 days post-reinoculation. Reproductive management was performed on all females and initiated when the females infected displayed IgG titers IFAT<1,024. From the average prolificacy indexes of each experimental group were estimated: total production of kilograms of live weight (total kg LW) of goats for slaughter, gross revenue and loss of gross revenue in U.S. dollars (US$), designed for a herd of 1,000 matrices. The unviable prolificacy indexes were 0.8 (GI), 1.2 (GII) and 0.2 (GIII). Clinical disorders affected 57.1% (GI), 75.0% (GII) and 16.7% (GIII) of the offspring of goats reinfected with T. gondii. Congenital toxoplasmosis in goats reinfected resulted in the loss of 26.5% of gross revenues, being GI (US$ 10,577.60 or 57.1%) and GII (US$ 12,693.12 or 60%) holders of the highest values and percentages of economic losses. It was found that congenital toxoplasmosis reinfection cause clinical disorders in goats chronically infected with T. gondii and their offspring with birth of unviable animals and loss of gross revenue, at different stages of pregnancy (40, 80 and 120 days of gestation)...

Nós determinamos os parâmetros reprodutivos e distúrbios clínicos em cabras gestantes infectadas e reinfectados com Toxoplasma gondii, e posteriormente, foi estimada a perda de receita bruta devido à toxoplasmose congênita. Das 25 fêmeas não prenhes negativas para T. gondii, 20 foram inoculadas oralmente (cepa ME 49) e, destas, 15 fêmeas gestantes infectadas cronicamente foram reinoculadas (cepa VEG), via oral, com oocistos de T. gondii. Cinco grupos foram formados (n = 5): GI, GII e GIII (reinoculações aos 40, 80 e 120 dias de gestação, respectivamente), GIV (inoculação) e GV (não inoculação). Exames clínicos e sorológicos foram realizados nos dias 0 (antes da inoculação), 3, 6 9, 15 e 21 e a cada sete dias após a inoculação. Os exames também foram realizados nos dias 3 e a cada sete dias de pós-reinoculação. Manejo reprodutivo foi realizado em todas as fêmeas e iniciou-se quando as fêmeas infectadas exibiram títulos de anticorpos IgG<1.024. A partir dos índices médios de prolificidade de cada grupo experimental foram estimados: a produção total de kg de peso vivo (total kg PV) de cabritos para o abate, receita bruta e perda de receita bruta em dólares norte-americanos (US$), projetadas para um rebanho de 1000 matrizes. Os índices de prolificidade inviáveis foram de 0,8 (GI), 1.2 (GII) e 0,2 (GIII). Distúrbios clínicos afetaram 57,1% (GI), 75,0% (GII) e 16,7% (GIII) das crias de cabras reinfectados com T. gondii. A toxoplasmose congênita em crias das cabras reinfectadas com T. gondii resultou na perda de 26,5% da receita bruta, sendo GI (US $ 10,577.60 e 57,1%) e GII (US $ 12,693.12 e 60.0%) os detentores dos mais altos valores e porcentagens de perdas econômicas. Verificou-se que a reinfecção toxoplásmica congênita causa distúrbios clínicos em cabras cronicamente infectadas com T. gondii e sua prole com o nascimento de animais inviáveis e perda de receita bruta, em diferentes fases da gestação (40, 80 e 120 dias de gestação)...

Programs for control of congenital toxoplasmosis.

Congenital toxoplasmosis can cause miscarriage and neurological and/or eye damage to the fetus. Since Austria and France established the prenatal screening, the prevalence of toxoplasmosis has declined from 50% to 35% and 84% to 44%, respectively. Other countries, such as the United Kingdom, have educational practices to reduce the risk of infection in seronegative pregnant women. In Brazil, prenatal screening is carried out in the states of Mato Grosso do Sul and Minas Gerais and the cities of Curitiba and Porto Alegre. In Londrina, state of Parana, the "Health Surveillance Program for Toxoplasmosis Acquired during Pregnancy and Congenital Toxoplasmosis" was established, which is based on serological screening, advising on prevention measures and quarterly serological monitoring in pregnant women that are initially seronegative, in addition to the monitoring of pregnant women and children with acute infection and case notification. In the first four years of implementation, the program evaluation showed a 63% reduction in the number of pregnant women and 42% in the number of children referred to reference services, resulting in the opening of vacancies for the care of patients with other diseases. As for medications, there was a 62% reduction in consumption of folic acid and 67% of sulfadiazine. Moreover, the definition of the protocols resulted in the standardization of care and safety for the decision-making by physicians. Therefore, as there are several protocols individualized in various departments and regions, the establishment of an ideal, consensual conduct with technical support, will result in implementing measures that will certainly save public resources, with the decrease in congenital toxoplasmosis.

Programas de controle da toxoplasmose congênita / Programs for control of congenital toxoplasmosis

A toxoplasmose congênita pode causar aborto e danos neurológicos e/ou oculares ao feto. Desde que a Áustria e a França estabeleceram a triagem pré-natal, a prevalência da toxoplasmose caiu de 50 por cento para 35 por cento e de 84 por cento para 44 por cento, respectivamente. Outros países, como o Reino Unido, adotam práticas educativas para reduzir o risco de infecção em gestantes soronegativas. No Brasil, a triagem pré-natal é realizada nos estados do Mato Grosso do Sul e Minas Gerais e nas cidades de Curitiba e Porto Alegre. Em Londrina, Paraná, foi implantado o "Programa de Vigilância da Toxoplasmose Adquirida na Gestação e Congênita", que se baseia na triagem sorológica, com orientação sobre as medidas de prevenção e monitoramento sorológico trimestral nas gestantes inicialmente soronegativas, além do acompanhamento das gestantes e crianças com infecção aguda e notificação dos casos. Nos primeiros quatro anos da implantação, a avaliação do programa demonstrou uma redução de 63 por cento no número de gestantes e de 42 por cento no número de crianças encaminhadas aos serviços de referência, resultando na liberação de vagas para o atendimento de pacientes com outras doenças. Quanto aos medicamentos, houve redução de 62 por cento no consumo de ácido folínico e de 67 por cento de sulfadiazina. Além disso, a definição dos protocolos resultou na padronização do atendimento e segurança para a tomada de decisões por parte dos médicos. Portanto, como existem diversos protocolos individualizados nos diversos serviços e regiões, o estabelecimento de uma conduta ideal e consensual, com respaldo técnico, implicará na adoção de medidas que, certamente, ocasionarão economia aos cofres públicos, com a diminuição da toxoplasmose congênita.

Congenital toxoplasmosis can cause miscarriage and neurological and/or eye damage to the fetus. Since Austria and France established the prenatal screening, the prevalence of toxoplasmosis has declined from 50 percent to 35 percent and 84 percent to 44 percent, respectively. Other countries, such as the United Kingdom, have educational practices to reduce the risk of infection in seronegative pregnant women. In Brazil, prenatal screening is carried out in the states of Mato Grosso do Sul and Minas Gerais and the cities of Curitiba and Porto Alegre. In Londrina, state of Parana, the "Health Surveillance Program for Toxoplasmosis Acquired during Pregnancy and Congenital Toxoplasmosis" was established, which is based on serological screening, advising on prevention measures and quarterly serological monitoring in pregnant women that are initially seronegative, in addition to the monitoring of pregnant women and children with acute infection and case notification. In the first four years of implementation, the program evaluation showed a 63 percent reduction in the number of pregnant women and 42 percent in the number of children referred to reference services, resulting in the opening of vacancies for the care of patients with other diseases. As for medications, there was a 62 percent reduction in consumption of folic acid and 67 percent of sulfadiazine. Moreover, the definition of the protocols resulted in the standardization of care and safety for the decision-making by physicians. Therefore, as there are several protocols individualized in various departments and regions, the establishment of an ideal, consensual conduct with technical support, will result in implementing measures that will certainly save public resources, with the decrease in congenital toxoplasmosis.

[Knowledge of toxoplasmosis among pregnant women, midwifes, medical students and obstetricians]. / Ocena stanu wiedzy dotyczacej toksoplazmozy wsród ciezarnych, poloznych, studentów medycyny i lekarzy polozników.

BACKGROUND: Knowledge of toxoplasmosis has been assessed among obstetricians, medical students, midwifes and pregnant women. The aims of the study were as follows: 1) evaluation of intra- and inter-group variation in correct answers to the questions included in the questionnaire used as a study tool; 2) evaluation of inter-group variation in answers to specialist and non-specialist questions; and 3) intra-group evaluation of self-assessed difficulty in completing the questionnaire. MATERIALS AND METHODS: In the prospective study, 310 participants were included: 109 pregnant women, 116 midwifes 85 physicians (including 69 specialists in OB/GYN) and 16 medical students. The anonymous questionnaire consisted of 26 questions, with four answers proposed for each question of which one was correct. RESULTS: There was no difference between correct answers among midwifes, physicians and medical students (p = 0.20), but the difference was found between the group of physicians and medical students and pregnant women as well as between midwifes and pregnant women (p < 0.001). Physicians, medical students and midwifes gave best answers to the non-specialist questions (p < 0.001), and midwifes obtained higher scores than pregnant women (p < 0.001). The mean percentage of correct answers to the specialist questions was among pregnant women (29%) showing a high level of randomness. The best answers to the non-specialist questions were found for physicians and midwifes (p = 0.93). However, there was a difference between the group of physicians and medical students and pregnant women and between midwifes and pregnant women in self-assessment of difficulty in completing the questionnaire (p < 0.001). CONCLUSIONS: Pregnant women assessed their knowledge of toxoplasmosis as least adequate, whereas midwifes, as most adequate. Pregnant women's knowledge about toxoplasmosis is poor. The group of physicians and medical students yielded evidently better score than pregnant women. There is a need for the improvement among prenatal care providers in both patient education and self-education.

Congenital toxoplasmosis--a report on the Danish neonatal screening programme 1999-2007.

OBJECTIVES: This paper reports on the national neonatal screening programme for congenital toxoplasmosis (CT) in Denmark conducted from 1999 to 2007, including background, basis for initiation of screening, methods, results, and finally reasons for the discontinuation of the screening. METHODS: A nationwide screening was conducted at Statens Serum Institut, including >98% newborns, and using filter paper eluates (Guthrie card, PKU card) obtained from newborns 5-10 days old. These were analysed for Toxoplasma gondii-specific antibodies (IgM), and if positive, then IgM (ISAGA). Confirmatory serology was performed on children and their mothers (IgM, IgG, IgA, dye test) where infection was suspected, and children with suspected or confirmed CT initiated a 3-month treatment regimen with pyrimethamine, sulfadiazine and folinic acid supplements. Selective cohorts were followed with regard to developmental and clinical outcome. RESULTS: A total of 100 children were diagnosed with CT in the screening period, and only 2 cases were detected outside of the screening programme. CT prevalence was 1.6 per 10,000 live-born infants. Follow-up studies showed new retinochoroidal lesions in affected children despite treatment. CONCLUSION: Screening was terminated August 2007, after it became apparent that no benefit of treatment could be shown. CT was evaluated using a Danish adaptation of the Uniform Screening Panel (ACMG), showing CT as an unlikely candidate for screening today. Whereas results might be comparable with other low-endemic countries with similar strains of T. gondii, neonatal screening and treatment might offer different results in regions with either high prevalence or different strains of T. gondii.

Azithromycin inhibits vertical transmission of Toxoplasma gondii in Calomys callosus (Rodentia: Cricetidae).

Toxoplasma gondii infection during pregnancy may cause severe consequences to the embryo. Current toxoplasmosis treatment for pregnant women is based on the administration of spiramycin or a drug combination as sulphadiazine-pyrimethamine-folinic acid (SPFA) in cases of confirmed fetal infection. However, these drugs are few tolerated and present many disadvantages due to their toxic effects to the host. The aim of this study was to evaluate the effectiveness of different treatments on the vertical transmission of T. gondii, including azithromycin, Artemisia annua infusion, spiramycin and SPFA in Calomys callosus as model of congenital toxoplasmosis. C. callosus females were perorally infected with 20 cysts of T. gondii ME49 strain at the day that a vaginal plug was observed (1st day of pregnancy - dop). Treatment with azithromycin, A. annua infusion, and spiramycin started at the 4th dop, while the treatment with SPFA started at the 14th dop. Placenta and embryonic tissues were collected for morphological and immunohistochemical analyses, mouse bioassay and PCR from the 15th to 20th dop. No morphological changes were seen in the placenta and embryonic tissues from females treated with azithromycin, spiramycin and SPFA, but embryonic atrophy was observed in animals treated with A. annua infusion. Parasites were found in the placenta and fetal (brain and liver) tissues of animals treated with SPFA, A. annua infusion and spiramycin, although the number of parasites was lower than in non-treated animals. Parasites were also observed in the placenta of animals treated with azithromycin, but not in their embryos. Bioassay and PCR results confirmed the immunohistochemical data. Also, bradyzoite immunostaining was observed only in placental and fetal tissues of animals treated with SPFA. In conclusion, the treatment with azithromycin showed to be more effective, since it was capable to inhibit the vertical transmission of T. gondii in this model of congenital toxoplasmosis.

Toxoplasmosis congénita: revisión / Congenital toxoplasmosis: a review

La forma congénita de infección por Toxoplasma gondii se produce a partir de una primo infección gestacional con consecuencias en distintos órganos del feto, especialmente oculares (coriorretinitis), SNC (hidrocefalia, convulsiones) y sistémicos(hepatoesplenomegalia), aunque entre el 80 y 90% son formas subclínicas. El diagnóstico se realiza mediante estudio serológico materno, dependiendo el riesgo de infección fetal del trimestre en que se produzca la seroconversión. Debido a la ausencia de estudios sobre la eficacia del tratamiento prenatal, se administrará a la madre con primoinfección tratamiento con espiramicina hasta conocer los resultados delos estudios complementarios. Ante infección en el recién nacido, se instaurará tratamiento con pirimetamina, sulfadiazina y ácido fólico, siendo el objetivo la disminución del riesgo de secuelas a largo plazo. El cribado gestacional es uno de los puntos de controversia, ya que tanto el gasto sanitario como el nivel de falsos + es elevado. Los programas de educación sanitaria han logrado disminuir en algunos países la tasa de infección al 50%

The congenital form of Toxoplasmga ondii infection is caused by primary maternal infection, with consequences in different fetal systems, especially the ocular system (chorioretinitis) and central nervous system (hydrocephalu, seizures), as well as systemic involvement(hepatosplenomegaly), although between 80% and 90% of the resulting disorders are subclinical. The diagnosis involves maternal serology, as the risk of fetal infection depends on the trimester in which seroconversion occurs. Given the lack of studies on the efficacy of prenatal treatment, spiramycin should be administered to pregnant women with primary infection until the results of complementary studies are known. Should the new born be infected, treatment with pyrimethamine, sulfadiazine and folic acid should be begunin the attempt to reduce the risk of long-term sequelae. Prenatal screening is a controversial issue since both the health care costs and rate of false positives are high. In some countries, health education programs have resulted in a decrease in the rate of infection of 50%

Achados audiológicos na toxoplasmose congênita / Audiological findings in congenital toxoplasmosis

O embrião ou feto, durante a gestação, ou o recém-nascido no momento do parto, pode ser afetado pelas infecções congênitas. Dentre estas, temos a toxoplasmose, que ocorre como conseqüência à contaminação da criança pelo protozoário Toxoplasma gondii, por via transplacentária hematogênica (WILSON et al., 1980).O objetivo deste trabalho foi verificar a prevalência de deficiência auditiva periférica e/ou alteração do processamento auditivo central em crianças de 0 a 2 anos de idade, portadoras de toxoplasmose congênita. As crianças, num total de 24, foram submetidas à avaliação audiológica completa. Após análise dos dados obtidos, verificamos que 54,2 por cento das crianças não apresentou alteração auditiva, 12,5 por cento apresentou alteração periférica transitória e 33,3 por cento alteração do Processamento Auditivo Central (PAC). Diante dos achados, pudemos concluir que a Toxoplasmose Congênita é um fator etiológico importante para alteração do PAC.

Toxoplasmosis congénita: un problema vigente en Chile: análisis de 15 casos clínicos / Congenital toxoplasmosis: a current problem in Chile: analysis of 15 clinical cases

Se analiza el problema de la toxoplasmosis congénita mediante el estudio de quince casos, cuatro lactantes con infección aguda y once niños con compromiso acular. La importancia del reconocimiento oportuno de la infección en el recién nacido y lactante, basada en la sospecha clínica (síndrome de TORCH y examen de fondo de ojo) y el diagnóstico serológico precoz que confirma la etiología, se discute en relación con el efecto curativo del tratamiento específico. La mayoría de los casos se diagnosticaron y trataron en forma tardía. En cinco niños tratados precozmente se obtuvo resultado satisfactorio, evitándose la muerte del recién nacido, disminuyendo el desarrollo de la infección y la aparición de reactivaciones, aunque persistieron secuelas a nivel del SNC. En los casos restantes, se observó sólo un efecto parcial del tratamiento. Se concluye que la toxoplasmosis congénita es un problema vigente en Chile y que la mayoría de los casos no se diagnostican oportunamente. Se recomienda intensificar su detección a nivel clínico, porque se dispone de drogas específicas que, aplicadas en forma precoz, pueden prevenir o aminorar el desarrollo de secuelas en el SNC

Screening for toxoplasmosis in pregnant women: presentation of a screening programme in the former "East"-Germany, and the present status in Germany.

The results of the screening programme (including the examination of fetal IgM) in East-Germany, related to the efficiency of therapy (pyrimethamine/sulfonamid) of the fetal infection risk are presented. For comparison the results of a prospective study of toxoplasmosis in pregnancy (n = 1697) without therapy, and follow up of the connatal infected infants to the age of 9/10 years old are shown. Recommendations for the diagnostic and therapeutical management in Germany for the future are presented.

Screening programme for congenital toxoplasmosis in France.

The high prevalence of Toxoplasma gondii infection in France led to the establishment of a national screening programme. Preventive measures were progressively introduced, and these became compulsory in 1978 with the result that the incidence of congenital toxoplasmosis is now markedly reduced. Further improvements may include more systematic sampling from women before pregnancy, better and adequate health education and centralized notification of both maternal and congenital cases of toxoplasmosis.

Linear areas of echogenicity in the thalami and basal ganglia of neonates: an expanded association. Work in progress.

A retrospective review of 2,320 neonatal cranial sonograms obtained in 1,324 patients identified 25 patients with areas of echogenicity in their thalami and basal ganglia that were of a linear or branching linear distribution. Four of these patients had cytomegalovirus infection. Other major diagnoses encountered included Down syndrome, trisomy 13 syndrome, neonatal asphyxia, non-immune hydrops, and fetal alcohol syndrome. Results of the study suggest a broader etiologic basis for linear areas of echogenicity in the basal ganglia and thalami of children than has previously been reported. These patients warrant complete screening for possible in utero infection and perhaps also chromosomal analysis.

Hypothalamo-pituitary dysfunction in congenital toxoplasmosis.

Three patients with congenital toxoplasmosis and hypothalamo-pituitary dysfunction are reported. All three children were growth hormone (GH) deficient, two were gonadotropin deficient and one had precocious puberty in addition to central diabetes insipidus (DI). It is suggested that congenital toxoplasmosis might result in a neuro-endocrine disturbance and thus be an organic cause of hypopituitarism. Pituitary function and growth should be monitored in children with congenital toxoplasmosis.

[Toxoplasmosis hypothalamic syndromes in children]. / Toksoplazmoznye gipotalamicheskie sindromy u detei.

Immunological studies of 1245 children with diseases of the nervous system and their mothers detected that in 9.0 +/- 0,7% they were due to toxoplasmosis. Clinico-physiological studies of 144 children with inborn neurotoxoplasmosis demonstrated that in pre- and pubertal periods the prevalent symptoms may be disorders of the hypothalamus. The clinical traits of toxoplasmotic syndromes in children are described.