Efecto del tratamiento prenatal con espiramicina en la frecuencia de retinocoroiditis por toxoplasmosis congénita en una cohorte colombiana / Effect of antenatal spiramycin treatment on the frequency of retinochoroiditis due to congenital toxoplasmosis in a Colombian cohort

Resumen Introducción. La toxoplasmosis de la gestación es frecuente y grave. Hasta ahora no hay consenso sobre la utilidad del tratamiento para prevenir complicaciones oculares en el neonato. En la actualidad, uno de los medicamentos utilizados en las madres diagnosticadas es la espiramicina oral. Infortunadamente, en algunas mujeres gestantes no se hace el diagnóstico prenatal y, por esta u otras razones, no reciben el tratamiento. Objetivo. Describir la relación entre el tratamiento con espiramicina durante el embarazo en madres con toxoplasmosis de la gestación y la presentación de toxoplasmosis ocular en los recién nacidos. Materiales y métodos. Se llevó a cabo un estudio observacional descriptivo de serie de casos. Se evaluó una serie prospectiva de pacientes con toxoplasmosis de la gestación durante tres años de seguimiento en el Servicio de Retinología de la Clínica Universitaria Bolivariana de Medellín. Resultados. Se registraron 23 madres con diagnóstico de toxoplasmosis de la gestación. Quince de ellas (65 %) recibieron durante la gestación tratamiento con espiramicina en dosis de 3 g al día; uno de los neonatos (6,6 %) presentó toxoplasmosis ocular. De las ocho (35 %) pacientes que no recibieron tratamiento, cinco (62,5 %) tuvieron hijos con compromiso ocular por toxoplasma. La razón de momios (odds ratio, OR) del efecto protector contra dicho compromiso en los pacientes cuyas madres recibieron tratamiento fue de 0,04 (IC95% 0,00-0,67), con valor de p menor de 0,01 en la prueba exacta de Fisher. Solo se evidenció compromiso del sistema nervioso central por toxoplasmosis mediante las imágenes de tomografía o ecografía cerebral en dos (14 %) pacientes de las 14 en quienes se hicieron estos estudios. Los dos pacientes presentaron, además, compromiso ocular; ambos fueron diagnosticados en el momento del nacimiento y sus madres no habían recibido tratamiento prenatal. Conclusiones. Estos resultados evidencian que el tratamiento con espiramicina durante el embarazo en la toxoplasmosis de la gestación redujo en 96 % (IC95% 33-100 %) el riesgo relativo de presentar la enfermedad en el recién nacido.

Abstrat Introduction: Gestational toxoplasmosis is frequent and severe. There is still debate about the benefits of treatment against ocular manifestations in the newborn. Spiramycin treatment is used for this purpose, unfortunately prenatal diagnosis is sometimes delayed and pregnant women are not treated. Objective: To describe the relationship between treatment with spiramycin during pregnancy in mothers with gestational toxoplasmosis and development of ocular toxoplasmosis in newborns. Materials and methods: We conducted a descriptive study of a case series. We evaluated a prospective cohort of patients diagnosed with gestational toxoplasmosis during three years at the Retinology Service at the Clínica Universitaria Bolivariana in Medellín. Results: Gestational toxoplasmosis was found in 23 mothers; 15 (65%) were treated during pregnancy with 3 g per day of spiramycin, eight (35%) patients were untreated. In the treated group just one newborn developed ocular toxoplasmosis (6.6%), in contrast with five (62.5%) of the eight patients who did not receive treatment. These results suggest that pregnancy treatment reduces the relative risk of ocular toxoplasmosis in the newborn by 96% (95% CI: 33 - 100%). Only two (14%) of the patients who were evaluated, had nervous system involvement related to toxoplasmosis in CT scan or cerebral ultrasound. These two patients also developed ocular pathology and were diagnosed at the time of birth, so they did not received antenatal treatment. Conclusions: A protective effect was found against the ocular involvement in patients whose mother received treatment with spiramycin (OR=0.04;95% CI: 0.00-0.67), p<0.01 (Fisher's Exact Test).

Genetic polymorphism for IFNγ +874T/A in patients with acute toxoplasmosis / Polimorfismo genético para IFNγ +874T/A em pacientes com toxoplasmose aguda

INTRODUCTION: A single nucleotide polymorphism (SNP) in the gene encoding gamma interferon influences its production and is associated with severity of infectious diseases. This study aimed to evaluate the association of IFNγ+874T/A SNP with duration of disease, morbidity, and development of retinochoroiditis in acute toxoplasmosis. METHODS: A case-control study was conducted among 30 patients and 90 controls. RESULTS: Although statistical associations were not confirmed, A-allele was more common among retinochoroiditis cases and prolonged illness, while T-allele was more frequent in severe disease. CONCLUSIONS: Despite few cases, the results could indicate a relation between IFNγ+874T/A single nucleotide polymorphism and clinical manifestations of toxoplasmosis.

INTRODUÇÃO: Um polimorfismo de nucleotideo único (SNP) no gene codificante para interferon gama influencia a sua produção e pode estar associado à gravidade de diversas doenças infecciosas. O objetivo deste estudo foi avaliar a associação entre SNP para IFNγ+874T/A com a duração da doença, a morbidade e o desenvolvimento de retinocoroidite na toxoplasmose aguda. MÉTODOS: Estudo de caso-controle incluindo 30 pacientes e 90 controles. RESULTADOS: Apesar da ausência de associação estatística, o alelo A foi mais comum entre os casos com retinocoroidite e doença prolongada e o alelo T nas formas mais severas. CONCLUSÕES: Os dados encontrados sugerem uma relação entre o polimorfismo de base única em IFNγ+874T/A com a morbidade e com o desenvolvimento de retinocoroidite por toxoplasmose.

Anti-Apoptotic Effects of SERPIN B3 and B4 via STAT6 Activation in Macrophages after Infection with Toxoplasma gondii

Toxoplasma gondii penetrates all kinds of nucleated eukaryotic cells but modulates host cells differently for its intracellular survival. In a previous study, we found out that serine protease inhibitors B3 and B4 (SERPIN B3/B4 because of their very high homology) were significantly induced in THP-1-derived macrophages infected with T. gondii through activation of STAT6. In this study, to evaluate the effects of the induced SERPIN B3/B4 on the apoptosis of T. gondii-infected THP-1 cells, we designed and tested various small interfering (si-) RNAs of SERPIN B3 or B4 in staurosporine-induced apoptosis of THP-1 cells. Anti-apoptotic characteristics of THP-1 cells after infection with T. gondii disappeared when SERPIN B3/B4 were knock-downed with gene specific si-RNAs transfected into THP-1 cells as detected by the cleaved caspase 3, poly-ADP ribose polymerase and DNA fragmentation. This anti-apoptotic effect was confirmed in SERPIN B3/B4 overexpressed HeLa cells. We also investigated whether inhibition of STAT6 affects the function of SERPIN B3/B4, and vice versa. Inhibition of SERPIN B3/B4 did not influence STAT6 expression but SERPIN B3/B4 expression was inhibited by STAT6 si-RNA transfection, which confirmed that SERPIN B3/B4 was induced under the control of STAT6 activation. These results suggest that T. gondii induces SERPIN B3/B4 expression via STAT6 activation to inhibit the apoptosis of infected THP-1 cells for longer survival of the intracellular parasites themselves.

Gene Expression Profiles in Genetically Different Mice Infected with Toxoplasma gondii: ALDH1A2, BEX2, EGR2, CCL3 and PLAU

Toxoplasma gondii can modulate host cell gene expression; however, determining gene expression levels in intermediate hosts after T. gondii infection is not known much. We selected 5 genes (ALDH1A2, BEX2, CCL3, EGR2 and PLAU) and compared the mRNA expression levels in the spleen, liver, lung and small intestine of genetically different mice infected with T. gondii. ALDH1A2 mRNA expressions of both mouse strains were markedly increased at day 1-4 postinfection (PI) and then decreased, and its expressions in the spleen and lung were significantly higher in C57BL/6 mice than those of BALB/c mice. BEX2 and CCR3 mRNA expressions of both mouse strains were significantly increased from day 7 PI and peaked at day 15-30 PI (P<0.05), especially high in the spleen liver or small intestine of C57BL/6 mice. EGR2 and PLAU mRNA expressions of both mouse strains were significantly increased after infection, especially high in the spleen and liver. However, their expression patterns were varied depending on the tissue and mouse strain. Taken together, T. gondii-susceptible C57BL/6 mice expressed higher levels of these 5 genes than did T. gondii-resistant BALB/c mice, particularly in the spleen and liver. And ALDH1A2 and PLAU expressions were increased acutely, whereas BEX2, CCL3 and EGR2 expressions were increased lately. Thus, these demonstrate that host genetic factors exert a strong impact on the expression of these 5 genes and their expression patterns were varied depending on the gene or tissue.

Toxoplasmose congênita / Congenital toxoplasmosis

Toxoplasmose é causada por infecção pelo parasita protozoário Toxoplasma gondii. Foram revisados aspectos da fisiopatologia da toxoplasmose congênita. As manifestações da toxoplasmose congênita no feto ou neonato são imprevisíveis, variando desde o óbito intra-uterino, retardo mental, convulsões, cegueira, hidrocefalia e coriorretinite até lesões menos severas, em que as manifestações da toxoplasmose congênita podem não ser aparentes até a segunda ou terceira décadas de vida. Testes sorológicos são utilizados para o diagnóstico da infecção aguda na gestante e na criança. A terapêutica mais utilizada e, provavelmente, mais efetiva é a combinação de pirimetamina, sulfadiazina e ácido folínico.

Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii. Some aspects of the physiopathology of the congenital toxoplasmosis were revised. Manifestations of congenital toxoplasmosis in the fetus and the newborn are unpredictable. They range from intra-uterine death, mental retardation, seizures, blindness, hydrocephalia and chorioretinitis to less severe lesions in which manifestations of congenital toxoplasmosis may not become apparent until the second or third decades of life. Serological tests are used to diagnose acute infection in pregnant women or in children. The most commonly used therapeutic regimen, and probably the most effective, is the combination of pyrimethamine with sulfadiazine and folinic acid.

Some molecular aspects in schistosomiasis mansoni and toxoplasmosis

The IL-2 and IL-4 cytokines production represent cellular Th1 and Th2 immune responses respectively were associated with chronic schistosomiasis mansoni [stages 1-4] and chronic toxoplasmosis gondii. In the hepatosplenic schistosomiasis, the level of IL-2 and disease stage increased in parallel [P< 0.05, <0.01, <0.01 and <0.001 in stages 1, 2, 3 and 4 respectively], whereas, IL- 4 was highly significantly increased in stage 1 than control [P < 0.001], then decreased to lower levels. The mean concentrations of IL-2 and IL-4 in patients with T. gondii were higher compared to control being more marked in Th-2 [P < 0.001] versus IL-4 [P < 0.01]. The data indicated that there are patterns of cytokine expression characteristic of type 1 and type 2 responses in vivo, with the ultimate goal of being able to manipulate the response to minimize inflammation and fibrosis for clinical benefit

Peculiaridades da toxoplasmose ocular no Rio Grande do Sul / Peculiarities of ocular toxoplasmose in Rio Grande do Sul, Brazil

Observaçöes clínicas, estudos sorológicos e trabalhos experimentais realizado durante os 10 últimos anos no Rio Grande do Sul, nos tem possibilitado detectar certas características inusuais da toxoplasmose ocular diferentes às encontradas em outras regiöes do mundo. Epidemiologicamente, levando-se em conta a origem dos pacientes, podemos dividir o Estado em três regiöes principais: a) Encosta do Nordeste e Alto Uruguai, b) Planalto Médio e Depressäo Central; c) Campanha. A maioria dos pacientes foram oriundos da Regiäo da Encosta, muito menos provinham da Depressäo Central e quase nenhum da Campanha. As razöes dessas variáveis na prevalência desta doença podem ser de ordem geográfica e climática assim como culturais e étnicas. Todavia, a possível presença de diferentes cepas do parasita näo pode ser descartada. Outro fato atípico encontrado é o grande número de casos de toxoplasmose familiar. Nove famílias foram estudadas nas quais vários membros estavam afetados, seja por lesöes ativas ou cicatriciais. Deve-se levar em consideraçäo a possibilidade de que muitos dos casos possam näo ser congênitos, mas adquiridos de apariçäo tardía. Estudos genéticos dos antigenos HLA nestas populaçöes e famílias poderiam ajudar a esclarecer esses problemas. Um outro fato refere-se aos aspectos morfológicos das lesöes de retinocoroidite. Estas costumam começar em uma pequena zona central, estendo-se concentricamente em forma tridimensional, até a periferia e esclera, até atingir seu máximo grau. Após, o processo de cicatrizaçiao começa centripetamente desde a periferia até o centro, onde a necrose e os fenómenos inflamatórios säo habitualmente mais intensos e duradouros. A correlaçäo deste padräo patológico com os fenômenos hétero e auto-imunes que acontecem neste tipo de lesäo ainda está por ser descoberta