Pathogenicity and phenotypic sulfadiazine resistance of Toxoplasma gondii isolates obtained from livestock in northeastern Brazil

Toxoplasma gondii is the causative protozoan agent of toxoplasmosis, which is a common infection that is widely distributed worldwide. Studies revealed stronger clonal strains in North America and Europe and genetic diversity in South American strains. Our study aimed to differentiate the pathogenicity and sulfadiazine resistance of three T. gondii isolates obtained from livestock intended for human consumption. The cytopathic effects of the T. gondii isolates were evaluated. The pathogenicity was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using a CS3 marker and in a rodent model in vivo. Phenotypic sulfadiazine resistance was measured using a kinetic curve of drug activity in Swiss mice. IgM and IgG were measured by ELISA, and the dihydropteroate synthase (DHPS) gene sequence was analysed. The cytopathic effects and the PCR-RFLP profiles from chickens indicated a different infection source. The Ck3 isolate displayed more cytopathic effects in vitro than the Ck2 and ME49 strains. Additionally, the Ck2 isolate induced a differential humoral immune response compared to ME49. The Ck3 and Pg1 isolates, but not the Ck2 isolate, showed sulfadiazine resistance in the sensitivity assay. We did not find any DHPS gene polymorphisms in the mouse samples. These atypical pathogenicity and sulfadiazine resistance profiles were not previously reported and served as a warning to local health authorities.

Afatinib Reduces STAT6 Signaling of Host ARPE-19 Cells Infected with Toxoplasma gondii

Specific gene expressions of host cells by spontaneous STAT6 phosphorylation are major strategy for the survival of intracellular Toxoplasma gondii against parasiticidal events through STAT1 phosphorylation by infection provoked IFN-γ. We determined the effects of small molecules of tyrosine kinase inhibitors (TKIs) on the growth of T. gondii and on the relationship with STAT1 and STAT6 phosphorylation in ARPE-19 cells. We counted the number of T. gondii RH tachyzoites per parasitophorous vacuolar membrane (PVM) after treatment with TKIs at 12-hr intervals for 72 hr. The change of STAT6 phosphorylation was assessed via western blot and immunofluorescence assay. Among the tested TKIs, Afatinib (pan ErbB/EGFR inhibitor, 5 µM) inhibited 98.0% of the growth of T. gondii, which was comparable to pyrimethamine (5 µM) at 96.9% and followed by Erlotinib (ErbB1/EGFR inhibitor, 20 µM) at 33.8% and Sunitinib (PDGFR or c-Kit inhibitor, 10 µM) at 21.3%. In the early stage of the infection (2, 4, and 8 hr after T. gondii challenge), Afatinib inhibited the phosphorylation of STAT6 in western blot and immunofluorescence assay. Both JAK1 and JAK3, the upper hierarchical kinases of cytokine signaling, were strongly phosphorylated at 2 hr and then disappeared entirely after 4 hr. Some TKIs, especially the EGFR inhibitors, might play an important role in the inhibition of intracellular replication of T. gondii through the inhibition of the direct phosphorylation of STAT6 by T. gondii.

Anti-Toxoplasma activities of methanolic extract of Sambucus nigra (Caprifoliaceae) fruits and leaves / Actividad anti-Toxoplasma de extractos metanólicos de frutos y hojas de Sambucus nigra (Caprifoliaceae)

Toxoplasma gondii is an obligatory intracellular parasite that infects a wide range of warm-blooded animals and humans. Considering the severity of toxoplasmosis, side effects of current treatments, and the contribution of the ethnopharmacological knowledge for the treatment of parasitic infections, the aim of the present study was to investigate the efficacy of methanolic extracts from the fruits and leaves of Sambucus nigra against tachyzoite of T. gondii. For this, fruits and leaves of S. nigra were collected from Mazandaran province, Iran, were dried under the shade, and powdered using a commercial electrical blender. For extractions, methanol was used as solvent. Virulent RH strain of T. gondii was maintained in mice and macrophages containing tachyzoites were aspirated from the peritoneal cavity. Four concentrations (5, 10, 25 and 50mg/mL) of S. nigra extract were incubated with infected macrophages for 30, 60, 120 and 180 minutes and the viability of the tachyzoites were evaluated by trypan blue staining. Results showed that S. nigra fruit extracts at the concentrations of 5 and 10mg/mL killed 100% of T. gondii tachyzoites after 60 and 120 minutes, respectively; and concentrations of 25 and 50mg/mL killed 100% of the tachyzoites after 30 minutes. Additionally, extract of S. nigra leaves, at the concentrations of 5, 10 and 25mg/mL after 180 minutes, and concentration of 50mg/mL after 60 minutes, resulted with the highest efficacy. Our results showed that S. nigra has acceptable efficacy in vitro and the parasiticidal effect of fruit extract was significantly better than leaf extract. However, in vivo efficacy of this extract needs further investigation. Rev. Biol. Trop. 63 (1): 7-12. Epub 2015 March 01.

Toxoplasma gondii es un parásito intracelular obligatorio que infecta a una gran variedad de animales y seres humanos. Teniendo en cuenta la gravedad de la toxoplasmosis, los efectos secundarios de los tratamientos actuales, y la contribución de los conocimientos etnofarmacológicos para el tratamiento de infecciones parasitarias, el objetivo del presente estudio fue investigar la eficacia de los extractos metanólicos de los frutos y hojas de Sambucus nigra contra el taquizoito de T. gondii. Para esto, se recogieron frutos y hojas de S. nigra en la provincia de Mazandaran, Irán, se secaron a la sombra, y se pulverizaron con una batidora eléctrica comercial. Para las extracciones, se empleó metanol como disolvente. La cepa virulenta RH de T. gondii se mantuvo en ratones y los macrófagos con taquizoitos se aspiraron de la cavidad peritoneal. Cuatro concentraciones (5, 10, 25 y 50mg/ mL) de extracto de S. nigra se encubaron con los macrófagos infectados durante 30, 60, 120 y 180 minutos y la viabilidad de los taquizoitos se evaluó mediante tinción con azul de tripano. Los resultados mostraron que los extractos de frutos de S. nigra en las concentraciones de 5 y 10mg/mL mataron al 100% de los taquizoitos de T. gondii después de 60 y 120 minutos, respectivamente; y las concentraciones de 25 y 50mg/mL mataron al 100% de los taquizoitos después de 30 minutos. Además, el extracto de hojas de S. nigra, en concentraciones de 5, 10 y 25mg/mL después de 180 minutos, y una concentración de 50mg/mL después de 60 minutos, resultaron más eficientes. Nuestros resultados mostraron que S. nigra tiene una eficacia aceptable in vitro y el efecto parasiticida del extracto de frutos fue significativamente mejor que el del extracto de hoja. Sin embargo, la eficacia in vivo de este extracto necesita más investigación.

Soroprevalência de anticorpos anti-Toxoplasma gondii em indígenas da etnia Terena, Mato Grosso do Sul, Brasil / Seroprevalencia de anticuerpos anti-Toxoplasma gondii en indígenas de la etnia Terena, Mato Grosso do Sul, Brasil / Seroprevalence of anti-Toxoplasma gondii antibodies among members of the Terena ethnic group, Mato Grosso do Sul, Brazil

Objetivo: avaliar por meio de inquérito soroepidemiológico a presença de anticorpos anti-Toxoplasma gondii na população indígena da etnia Terena, bem como reconhecer os prováveis mecanismos de transmissão do Toxoplasma gondii naquela comunidade. Métodos: para realização da pesquisa, coletou-se sangue venoso de 256 indígenas assintomáticos. O soro obtido do sangue foi congelado a - 20 °C até a realização dos exames. Realizou-se a sorologia por imunofluorescência Indireta (RIFI) e confirmação dos soros positivos por Enzyme-Linked Immunosorbent Assay (ELISA). Resultados: entre os 256 indígenas estudados, 67 (26,17) apresentaram anticorpos de classe IgG anti-T gondii, com títulos iguais ou superiores a 1:16. Não foi encontrada positividade para IgM em nenhuma das amostras analisadas. Conclusões: a soroprevalência de anticorpos anti-T. gondii entre os indígenas da etnia Terena indica que essa população teve um contato anterior com o parasito. O fator de risco identificado como provável responsável pela transmissão foi coabitação entre pessoas e gatos. A prevalência de soropositividade foi maior na faixa etária entre 21 e 25 anos(AU)

Objetivo: evaluar por medio de interrogatorio seroepidemiológico la presencia de anticuerpos anti-Toxoplasma gondii en la población indígena de la etnia Terena, así como reconocer los probables mecanismos de transmisión del Toxoplasma gondii en esa comunidad. Métodos: se recolectó sangre venosa de 256 indígenas asintomáticos. El suero obtenido de la sangre se congeló a - 20 °C hasta la realización de los exámenes. Se hizo la serología por inmunofluorescencia indirecta y la confirmación de los sueros positivos por ELISA (enzyme-linked immunosorbent assay). Resultados: entre los 256 indígenas estudiados, 67 (26,17 por ciento) presentaron anticuerpos de clase IgG anti- Toxoplasma gondii, con títulos iguales o superiores a 1:16. No se encontró positividad para IgM en las muestras analizadas. Conclusiones: la seroprevalencia de anticuerpos anti- Toxoplasma gondii entre los indígenas de la etnia Terena indica que esa población tuvo un contacto anterior con el parásito. El factor de riesgo identificado como probable responsable por la transmisión resultó la cohabitación entre personas y gatos. La prevalencia de seropositividad fue mayor en la franja etaria entre 21 y 25 años(AU)

Objective: by means of seroepidemiological interviews, determine the presence of anti-Toxoplasma gondii antibodies among the native Terena population, and identify the probable transmission mechanisms of Toxoplasma gondii in that community. Methods: venous blood was collected from 256 asymptomatic community members. The blood serum obtained was frozen to -20 °C until the tests were carried out. Indirect immunofluorescence serology was performed and positive sera were confirmed by ELISA (enzyme-linked immunosorbent assay). Results: of the 256 subjects studied, 67 (26.17 percent) had anti-Toxoplasma gondii IgG antibodies, with titers equal to of greater than 1:16. No positive results were obtained for IgM in the samples analyzed. Conclusions: the seroprevalence of anti-Toxoplasma gondii antibodies among members of the Terena ethnic group indicates that this population had a previous contact with the parasite. The risk factor identified as the probable cause of transmission was the presence of cats in households. Seropositivity was highest in the 21-25 age group(AU)

Gefitinib Inhibits the Growth of Toxoplasma gondii in HeLa Cells

Toxoplasma gondii is the causative agent of toxoplasmosis with symptoms of congenital neurological and ocular diseases and acquired lymphadenitis, retinochoroiditis, and meningoencephalitis. Small molecules which block the activity of protein kinases were tested in in vitro culture of T. gondii to find new therapeutic drugs of safer and more effective than the combined administration of pyrimethamine and sulfadoxine that sometimes provoke lethal Stevens-Johnson syndrome. Among them, Gefitinib and Crizotinib inhibited intracellular growth of T. gondii in HeLa cells by counting the number of T. gondii per parasitophorous vacuolar membrane whereas Sunitinib did not. Gefitinib inhibited the growth of T. gondii in a dose-dependent manner over 5 microM up to the tolerable concentration of HeLa cells and halted the division of the parasite immediately from the time point of treatment. Gefitinib inhibition suggests that tyrosine kinases of EGFR family or other homologous kinases of the parasite itself may be the target to cause the block of T. gondii growth.

Antiretroviral activity of protease inhibitors against Toxoplasma gondii / Terapia antiretroviral de inibidores da protease contra Toxoplasma gondii

The introduction of highly active antiretroviral therapy (HAART) has caused a marked reduction in the occurrence and severity of parasitic infections, including the toxoplasmic encephalitis (TE). These changes have been attributed to the restoration of cell-mediated immunity. This study was developed to examine the activity of six antiretroviral protease inhibitors (API) on Toxoplasma gondii tachyzoites. The six API showed anti-Toxoplasma activity, with IC50 value between 1.4 and 6.6 µg/mL. Further studies at the molecular level should be performed to clarify if the use of API could be beneficial or not for AIDS patients with TE.

La introducción de la terapia antirretroviral de alta efectividad ha causada una marcada reducción en la ocurrencia y curso clínico de las infecciones parasitarias, incluyendo la toxoplasmosis encefálica (TE). Estos cambios han sido atribuidos a la restauración celular. Este estudio fue desarrollado para examinar la actividad de seis inhibidores de proteasas antirretrovirales (IPA) sobre taquizoitos de Toxoplasma gondii. Los seis IPA mostraron actividad anti-Toxoplasma, con valores de CI50 entre 1.4 y 6.6 µg/mL. Futuros estudios a nivel molecular deben ser realizados, los cuales podrán delucidar si el uso de IPA pudiera beneficiar o no a los pacientes que sufren de TE.

In vitro action of antiparasitic drugs, especially artesunate, against Toxoplasma gondii / Ação in vitro de drogas antiparasitárias, especialmente artesunato, contra Toxoplasma gondii

INTRODUCTION: Toxoplasmosis is usually a benign infection, except in the event of ocular, central nervous system (CNS), or congenital disease and particularly when the patient is immunocompromised. Treatment consists of drugs that frequently cause adverse effects; thus, newer, more effective drugs are needed. In this study, the possible activity of artesunate, a drug successfully being used for the treatment of malaria, on Toxoplasma gondii growth in cell culture is evaluated and compared with the action of drugs that are already being used against this parasite. METHODS: LLC-MK2 cells were cultivated in RPMI medium, kept in disposable plastic bottles, and incubated at 36ºC with 5% CO2. Tachyzoites of the RH strain were used. The following drugs were tested: artesunate, cotrimoxazole, pentamidine, pyrimethamine, quinine, and trimethoprim. The effects of these drugs on tachyzoites and LLC-MK2 cells were analyzed using nonlinear regression analysis with Prism 3.0 software. RESULTS: Artesunate showed a mean tachyzoite inhibitory concentration (IC50) of 0.075µM and an LLC MK2 toxicity of 2.003µM. Pyrimethamine was effective at an IC50 of 0.482µM and a toxicity of 11.178µM. Trimethoprim alone was effective against the in vitro parasite. Cotrimoxazole also was effective against the parasite but at higher concentrations than those observed for artesunate and pyrimethamine. Pentamidine and quinine had no inhibitory effect over tachyzoites. CONCLUSIONS: Artesunate is proven in vitro to be a useful alternative for the treatment of toxoplasmosis, implying a subsequent in vivo effect and suggesting the mechanism of this drug against the parasite.

INTRODUÇÃO: Toxoplasmose é geralmente uma infecção benigna, exceto nos eventos de doença ocular, congênito e do sistema nervoso central, e particularmente quando o paciente é imunocomprometido. O tratamento consiste de drogas que frequentemente causam efeitos adversos, então novas drogas, mais efetivas são necessárias. Neste estudo, a possível atividade de artesunato, uma droga usada com sucesso no tratamento da malária, sobre o crescimento de Toxoplasma gondii em cultura celular é avaliado e comparado à ação de drogas que já estão sendo utilizadas contra este parasita. MÉTODOS: Células LLC-MK2 foram cultivadas em meio RPMI, mantidas em garrafas plásticas descartáveis e incubados a 36ºC com 5% CO2. Taquizoítos da cepa RH foram usados. As seguintes drogas foram testadas: artesunato, cotrimoxazol, pentamidina, pirimetamina, quinino e trimetoprima. Os efeitos dessas drogas sobre taquizoítos foram analisados por análise regressiva não linear com o software Prism 3.0. RESULTADOS: Artesunato mostrou uma concentração inibitória media (IC50) de 0,075µM e uma toxicidade sobre células LLC MK2 de 2,003µM. Pirimetamina foi efetiva a uma IC50 de 0,482µM e uma toxicidade de 11,178µM. Trimetoprima sozinha foi efetiva contra o parasita in vitro. Cotrimoxazol também foi efetivo contra o parasita, mas a concentrações mais altas que aquelas observadas para artesunato e pirimetamina. Pentamidina e quinino não tiveram efeitos inibitórios sobre os taquizoítos. CONCLUSÕES: Provou-se que artesunato in vitro pode ser uma alternativa útil para o tratamento da toxoplasmose, implicando um subsequente efeito in vivo e sugerindo o mecanismo desta droga contra o parasita.

Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives

Toxoplasma, which infects all eukaryotic cells, is considered to be a good system for the study of drug action and of the behavior of infected host cells. In the present study, we asked if thiosemicarbazone derivatives can be effective against tachyzoites and which morphological and ultrastructural features of host cells and parasites are associated with the destruction of Toxoplasma. The compounds were tested in infected Vero cell culture using concentration screens (0.1 to 20 mM). The final concentration of 1 mM was chosen for biological assay. The following results were obtained: 1) These new derivatives decreased T. gondii infection with an in vitro parasite IC50 percent of 0.2-0.7 mM, without a significant effect on host cells and the more efficient compounds were 2, 3 (thiosemicarbazone derivatives) and 4 (thiazolidinone derivative); 2) The main feature observed during parasite elimination was continuous morphological disorganization of the tachyzoite secretory system, progressive organelle vesiculation, and then complete disruption; 3) Ultrastructural assays also revealed that progressive vesiculation in the cytoplasm of treated parasites did not occur in the host cell; 4) Vesiculation inside the parasite resulted in death, but this feature occurred asynchronously in different intracellular tachyzoites; 5) The death and elimination of T. gondii was associated with features such as apoptosis-like stage, acidification and digestion of parasites into parasitophorous vacuoles. Our results suggest that these new chemical compounds are promising for the elimination of intracellular parasites by mainly affecting tachyzoite development at 1 mM concentration for 24 h of treatment.

Acidification of the parasitophorous vacuole containing Toxoplasma gondii in the presence of hydroxyurea

Toxoplasma gondii se multiplica dentro do vacúolo parasitóforo que não é reconhecido pela defesa primária não oxidativa de células hospedeiras: a fusão com organelas ácidas. Estudos anteriores mostraram que hidroxiuréia interrompeu a multiplicação dos parasitos intracelulares causando sua eliminação. No presente trabalho nós investigamos o mecanismo celular envolvido na destruição do Toxoplasma gondii intracelular. Marcadores vitais fluorescentes foram usados para observar a possível acidificação do vacúolo parasitóforo contendo Toxoplasma gondii na presença de hidroxiuréia. Células Vero infectadas com taquizoítos foram tratadas com hidroxiuréia por 12, 24 ou 48 horas. Fluorescência indicativa de acidificação foi observada no vacúolo parasitóforo quando as culturas foram incubadas na presença de laranja de acridina. Lyso Tracker red foi usado para determinar se os lisossomos estavam envolvidos no processo de acidificação. Uma fluorescência intensa foi observada depoisde 12 e 24 horas de incubação com hidroxiuréia, alcançando uma intensidade maior após 48 horas de tratamento. Citoquímica ultraestrutural para localização da enzima fosfatase ácida lisossomal foi realizada. As culturas infectadas e tratadas apresentaram produto de reação em vesículas se fundindo com o vacúolo ou associado com parasitas intravacuolares. Estes resultados sugerem que a fusão com lisossomos e acidificação do vacúoloparasitóforo causa a destruição dos parasitos na presença de hidroxiuréia.

Modulation of haematological and pathological changes caused by toxoplasma gondii in an experimental model of chronic infection

Wide spectrum of pathologic patterns is encountered in T. gondii infection, ranging from trivial pathology to fatal disease. The study was done to evaluate the ability of some drug groups to reverse the pathological changes caused by T. gondii infection. This evaluation was done, in vivo, in a rat model of chronic infection parallel to that in human. Lung, liver and brain specimens were taken in definite time points respecting the kinetics of infection in that model. Blood counts were done to all groups to evaluate efficacy and toxicity of drugs. A new combination of dipyridamole/ allopurinol was able to significantly reduce the pathology in all organs to almost the baseline pathology of chronic Toxoplasma infection. The relatively moderate protective effect of pyrimethamine/sulfadiazine combination was undermined by the toxic effects evidenced by pathology and haematological parameters. Spiramycin, in spite of proving safe, yet its protective effective is relatively weak in all organs especially in the brain where it seems to offer no protection

Measurement of IL-10 serum levels in balb/c mice treated with beta-1, 3 polyglucose or sulfadiazine and acutely infected by Toxoplasma gondii

Acute infection by Toxoplasma gondii leads to suppression of cell-mediated immunity, facilitating chronic infection. One of the causes of immunosuppression is Interleukin-10 (IL-10) production. Glucan is used to stimulate phagocytosis. Our objective was to study IL-10 induction in male BALB/c mice with acute T. gondii BTU-2 strain infection, glucan immunostimulation, and sulfadiazine treatment. Animals were distributed into 7 groups: G1: infected with T. gondii; G2: infected with T. gondii and treated with sulfadiazine; G3: infected with T. gondii and immunostimulated with glucan; G4: infected with T. gondii, immunostimulated with glucan, and treated with sulfadiazine; G5: imunostimulated with glucan; G6: treated with saline; and G7: treated with sulfadiazine. IL-10 levels were determined by ELISA; the highest levels were found in G2, G3 and G4, and the lowest in G1 (p<0.001). Groups G1 to G5 and G7 had substantially higher levels than G6 (p<0.001). In this study, the highest IL-10 levels were found in groups treated with glucan

Potential role of rolipram, a specific phosphodiestrase inhibitor, in preventing the establishment of a chronic state of toxoplasma gondii infection

Progression to a chronic state of the disease after an initial, mostly asymptomatic, acute phase is the normal fate of Toxoplasma gondii infection in immunocompetent hosts. Parasite reactivation of established chronic stage has serious manifestations on immunocompromised hosts. Tumor necrosis factor [TNF]- alpha, Interleukin [IL]-12 and cAMP have pivotal roles in tachyzoite to bradyzoite conversion and establishment of a chronic state of the disease. Rolipram, a specific phosphodiestrase inhibitor, has different regulatory roles on these factors. A daily oral dose of 10 mg/kg of rolipram was given to a group of mice, one week after T. gondii infection and for three weeks. Rolipram was found to have a great impact in preventing progression of chronic state and in mitigation of the pathology of this stage. Toxoplasma gondii tissue cyst load in mice brains has showed almost 4-fold reduction with the use of rolipram. The drug also mitigated the inflammation and pathologic processes in liver and more evident in the brain. Anti-Toxoplasma antibody titers are also significantly reduced in rolipram-treated group

Influence of calcium ion on host cell invasion and intracellular replication by Toxoplasma gondii

Toxoplasma gondii is an obligate intracellular protozoan parasite, which invades a wide range of hosts including humans. The exact mechanisms involved in its invasion are not fully understood. This study focused on the roles of Ca2+ in host cell invasion and in T. gondii replication. We examined the invasion and replication of T. gondii pretreated with several calcium modulators, the conoid extrusion of tachyzoites. Calmodulin localization in T. gondii were observed using the immunogold method, and Ca2+ levels in tachyzoites by confocal microscopy. In light microscopic observation, tachyzoites co-treated with A23187 and EGTA showed that host cell invasion and intracellular replication were decreased. The invasion of tachyzoites was slightly inhibited by the Ca2+ channel blockers, bepridil and verapamil, and by the calmodulin antagonist, calmidazolium. We observed that calcium saline containing A23187 induced the extrusion of tachyzoite conoid. By immunoelectron microscopy, gold particles bound to anti-calmodulin or anti-actin mAb, were found to be localized on the anterior portion of tachyzoites. Remarkably reduced intracellular Ca2+ was observed in tachyzoites treated with BAPTA/AM by confocal microscopy. These results suggest that host cell invasion and the intracellular replication of T. gondii tachyzoites are inhibited by the calcium ionophore, A23187, and by the extracellular calcium chelator, EGTA.

Mecanismos efectores del interferón gamma contra la infección por Toxoplasma gondii / Effector mechanisms of gamma interferon against Toxoplasma gondii

Toxoplasma gondii es un protozoario parásito de desarrollo intracelular. La enfermedad humana producida por T. gondii es una causa importante de morbilidad y mortalidad neonatal y en pacientes inmunodeprimidos. En esta reseña, se revisan los conocimientos actuales sobre los mecanismos efectores del interferón gamma (IFN gamma), la principal citocina protectora contra T. gondii, incluyendo los resultados que hemos obtenido en un modelo de infección in vitro de células humanas monocitarias (THP1). El IFN gamma protege las células humanas contra T. gondii por mecanismos diferentes a aquéllos con los que protege las células de ratón. En el modelo de infección de células THP1, el IFN gamma protege por dos mecanismos independientes. Un primer efecto es la reducción del porcentaje de células parasitadas, el cual está ligado a una disminución de la actividad PLA subíndice 2 parasitaria y celular. Se trata de un nuevo mecanismo efector del IFN gamma contra la infección toxoplásmica, diferente a los mecanismos parasiticidas y parasitostáticos previamente descritos. Un segundo efecto ocurre por interrupción del crecimiento parasitario intracelular a través de la activación de la enzima idoleamina-oxigenasa que degrada el triptófano, lo que constituye un efecto parasitostático. Contrariamente a lo que ocurre en el modelo de infección de células monocitarias de ratón, la producción de óxido nítrico (NO) no juega un papel determinante en los monocitos humanos

Avaliaçäo da eficácia da azitromicina e da pirimetamina, usadas isolada ou associadamente, no tratamento de infecçäo experimental de camundongos pelo Toxoplasma gondii / Evaluation of the efficacy of azithromycin and pyrimethamine, alone or in combination, for the treatment of experimental infection of mice with Toxoplasma gondii

Foi comprovada a eficácia da azitromicina e da pirimetamina no tratamento da infecçäo experimental de camundongos pelo Toxoplasma gondii. Houve administraçäo cotidiana, pela via oral de 200mg/kg e 12,5mg/kg, respectivamente durante dez dias. O uso dos medicamentos ocorreu mediante associaçäo ou näo e o emprego concomitante proporcionou o melhor resultado e convirá efetuar investigaçäo semelhante com cepa cistogênica do parasita

Toxoplasmosis cerebral en pacientes con SIDA / Brain toxoplasmosis in AIDS patients

El presente trabajo abarcó el período comprendido entre el año 1987 y agosto de 1994. Se diagnosticaron 25 pacientes con toxoplasmosis cerebrales (23 hombres y 2 mujeres), con una media de 35 años. Doce fueron heterosexuales y 11 homosexuales, todos en etapa Sida con repercusión general. Las manifestaciones clínicas más frecuentes fueron síndrome neurológico en 19 pacientes (síndrome motor deficitario 12, síndrome arquineocerebeloso 6, síndrome frontal 3, estado confusional l); síndrome febril prolongado 11; síndrome de hipertensión endocraneana 14; síndrome poliadenomegálico 7. La TAC mostró en 24 pacientes imágenes compatibles con toxoplasmosis. Se observaron frecuentemente infecciones asociadas de las cuales 14 fueron marcadoras de etapa evolutiva SIDA; (Candidiasis orofaríngea P pacientes, neumocistosis 6 pacientes), otras infecciones asociadas (lúes, Bk, CMV, herpes). Siete pacientes cursaron con clínica de toxoplasmosis sin otras infecciones intercurrentes. El diagnóstico fue tomográfico, clínico y serológico. No hubo confirmación parasitológica, mediante biopsia cerebral. La determinación de las poblaciones linfocitarias mostró cifras de T4 menores a 200 en 15 pacientes. La serología para toxoplasmosis mostró títulos altos de anticuerpos en 13 pacientes, con IgM positiva en 2 de ellos. La mayor eficacia terapéutica se obtuvo con la combinación de pirimetamina, sulfadiazina y ácido folínico, obteniéndose en 10 pacientes buena respuesta clínica y paraclínica

Azitromicina en el tratamiento de la toxoplasmosis aguda experimental / Azithromycin in the treatment of acute experimental toxoplasmosis

La toxoplasmosis es la zoonosis parasitaria más difundida en la naturaleza. Constituye una de las principales infecciones oportunistas en pacientes con SIDA. El tratamiento de primera elección es la asociación de pirimetamina y sulfadiazina, que se ve seriamente limitada por su alta frecuencia de reacciones adversas, lo que ha motivado la búsqueda de esquemas quimioterapéuticos alternativos. Se compara la eficacia de la azitromicina en el tratamiento de toxoplasmosis aguda, en relación a la asociación de pirimetamina y sulfadiazina, en un modelo de infección experimental en ratones, midiéndose la respuesta al tratamiento en días de sobrevida. La asociación de una mayor eficacia en nuestro estudio, por lo que seguiría siendo el esquema de elección en la toxoplasmosis aguda. Sin embargo, la azitromicina prolonga significativamente la sobreida de los ratones infectados con respecto al grupo de ratones no tratados