RESUMO
Little is known about the existence of drug-resistant Toxoplasma gondii strains and their possible impact on clinic outcomes. To expand our knowledge about the existence of natural variations on drug susceptibility of T. gondii strains in Brazil, we evaluated the in vitro and in vivo susceptibility to sulfadiazine (SDZ) and pyrimethamine (PYR) of three atypical strains (Wild2, Wild3, and Wild4) isolated from free-living wild birds. In vitro susceptibility assay showed that the three strains were equally susceptible to SDZ and PYR but variations in the susceptibility were observed to SDZ plus PYR treatment. Variations in the proliferation rates in vitro and spontaneous conversion to bradyzoites were also accessed for all strains. Wild2 showed a lower cystogenesis capacity compared to Wild3 and Wild4. The in vivo analysis showed that while Wild3 was highly susceptible to all SDZ and PYR doses, and their combination, Wild2 and Wild4 showed low susceptibility to the lower doses of SDZ or PYR. Interestingly, Wild2 presented low susceptibility to the higher doses of SDZ, PYR and their combination. Our results suggest that the variability in treatment response by T. gondii isolates could possibly be related not only to drug resistance but also to the strain cystogenesis capacity.
Assuntos
Antiprotozoários , Toxoplasma , Sulfadiazina/farmacologia , Sulfadiazina/uso terapêutico , Pirimetamina/farmacologia , Pirimetamina/uso terapêutico , Antiprotozoários/uso terapêutico , BrasilRESUMO
Chronic toxoplasmosis which is positively correlated with many neuropsychiatric problems has no curative treatment till now; due to the resistant tissue cysts especially in the brain. In search of an effective treatment, guanabenz-loaded polyethylene glycol poly lactic-co-glycolic acid (PEG-PLGA) nanoparticles was evaluated against chronic experimental toxoplasmosis. For this purpose, each mouse was infected with 10 cysts of Toxoplasma gondii (ME 49 strain). Treated mice received either guanabenz alone (5 mg/kg/day) in subgroup IIa or guanabenz-loaded nanoparticles by full dose in subgroup IIb or guanabenz-loaded nanoparticles by the half dose (2.5 mg/kg/day) in subgroup IIc. Subgroup Ie was treated by pyrimethamine and sulfadiazine. The treatment started on day 25 post-infection for 19 successive days. Then Parasitological, histopathological, immunohistochemical, immunological and ultrastructural morphological studies were performed. The results showed that: subgroup IIb showed the highest statistically significant reduction in the neuroinflammation and brain tissue cysts (77%) with a significant higher efficacy in comparison with pyrimethamine and sulfadiazine and showed the highest level of IFN-γ, while the lowest level was in subgroup IIa. All group II mice showed similar changes of depression and compression of the wall of the cyst. This is marked in subgroup IIb with release of crescent shaped bradyzoite outside the cyst. PEG-PLGA nanoparticles had no toxic effect on the liver or the kidney of the mice. It could be concluded that guanabenz-loaded PEG-PLGA nanoparticles could be promising and safe for treatment of chronic toxoplasmosis.
Assuntos
Guanabenzo , Nanopartículas , Toxoplasma , Toxoplasmose , Animais , Camundongos , Guanabenzo/farmacologia , Guanabenzo/uso terapêutico , Nanopartículas/uso terapêutico , Pirimetamina/uso terapêutico , Pirimetamina/farmacologia , Sulfadiazina/uso terapêutico , Sulfadiazina/farmacologia , Toxoplasmose/tratamento farmacológicoRESUMO
Toxoplasma gondii infects one-third of the world population. For decades, it has been considered a silent lifelong infection. However, chronically T. gondii-infected persons may present psychiatric and neurocognitive changes as anxiety, depression, and memory loss. In a model of long-term chronic infection, behavioral alterations parallel neuroinflammation and systemic high cytokine levels, and may reflect brain cyst load. Recent findings support that in chronic infection an active parasite-host interplay involves an immune-mediated control of tissue cysts. Here, we tested the idea that etiological treatment in chronic phase may add advantage to intrinsic immune-mediated cyst control and impact behavioral changes. Thus, we combined sulfadiazine-plus-pyrimethamine (S+P), the first-choice therapy for toxoplasmosis, to study the association of brain cyst load and biological processes related to the immune response (neuroinflammation, blood-brain barrier -BBB- disruption and serum cytokine levels), with behavioral and neurocognitive changes of long-term chronic infection. Female C57BL/6 mice (H-2b) were infected (5 cysts, ME-49 strain) and treated with S+P from 30 to 60 days postinfection (dpi), compared with vehicle (Veh)-treated and noninfected controls. At endpoints (pre-therapy, 30 dpi; S+P therapy, 60 dpi; after ceased therapy, 90 dpi), independent groups were subjected to behavioral tests, and brain tissues and sera were collected. Multiple behavioral and neurocognitive changes were detected in the early (30 dpi) and long-term (60 and 90 dpi) chronic infection. S+P therapy resolved locomotor alterations, anxiety, and depressive-like behavior, partially or transiently ameliorated hyperactivity and habituation memory loss. Analysis after therapy cessation showed that S+P therapy reduced the number of stimuli required for aversive memory consolidation. S+P therapy resulted in reduced brain cyst load, neuroinflammation and BBB disruption, and lowered systemic Th1-cytokine levels. Correlation analysis revealed association between IFNγ, TNF and MCP-1/CCL2 serum levels, brain cyst load and behavioral and neurocognitive alterations. Moreover, principal-component analysis (PCA-2D and 3D projections) highlighted distinction between clusters (noninfected; Veh-treated and S+P-treated infected). Thus, our data suggest that S+P therapy added gain to intrinsic brain cyst control and, direct or indirectly, ameliorated inflammation-related alterations, traits associated with behavioral and neurocognitive alterations.
Assuntos
Encéfalo , Pirimetamina , Sulfadiazina , Toxoplasmose , Animais , Encéfalo/parasitologia , Citocinas , Feminino , Inflamação/tratamento farmacológico , Transtornos da Memória/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Pirimetamina/farmacologia , Pirimetamina/uso terapêutico , Sulfadiazina/farmacologia , Sulfadiazina/uso terapêutico , Toxoplasmose/tratamento farmacológico , Toxoplasmose/patologiaRESUMO
A toxoplasmose é uma doença proveniente do Toxoplasma gondii, um protozoário que tem os felinos como seu hospedeiro definitivo e os mamíferos e aves como seu hospedeiro intermediário. Tem um curso benigno e autolimitado quando acomete um indivíduo imunocompetente, no entanto a infecção durante a gestação acarreta até 50% de chance de toxoplasmose congênita, podendo causar danos severos ao feto. A virulência dos genótipos encontrados nas Américas Central e do Sul é a mais alta, comparada a Europa e América do Norte, tendo a doença um comportamento mais agressivo. Os estudos relatam a diminuição da infecção fetal em até 60% com o uso da espiramicina, usada ainda na profilaxia. Este artigo discute sobre a triagem materna pré-natal e sua necessidade, a profilaxia e o tratamento da infecção fetal ainda intraútero, com o objetivo de diminuir a transmissão vertical e as sequelas neonatais com suas implicações ao longo da vida.(AU)
Toxoplasmosis it is a disease originating from Toxoplasma gondii, a protozoan that has felines at as ultimate host and mammals and birds at as intermediate host. Has a benign and self-limiting course when affects immunocompetent individual, however, infection during pregnancy leads 50% chance of congenital toxoplasmosis and can cause severe damage to the fetus. The virulence of genotypes found in Central and South America is the highest compared to Europe and North America, having the disease a more aggressive behavior. Studies report a reduction in fetal infection 60% with the use spiramycin still used for prophylaxis. This article discusses prenatal maternal screening, prophylaxis and treatment of fetal infection still in utero with the objective of decreasing vertical transmission and neonatal sequelae with their lifelong implications.(AU)
Assuntos
Humanos , Feminino , Gravidez , Toxoplasma , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/prevenção & controle , Toxoplasmose Congênita/tratamento farmacológico , Cuidado Pré-Natal , Pirimetamina , Sulfadiazina/uso terapêutico , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Espiramicina/uso terapêutico , Feto , Amniocentese , Líquido Amniótico/parasitologiaRESUMO
Purpose: This study evaluated if Toxoplasma gondii infection and the drug-associated infection modifies the brain radiopharmaceutical Ethylene Cystine Diethylester Dihydrochloride (99mTc-ECD) biodistribution in mice.Materials and methods: A total of 18 mice were divided into 3 groups. Control group (C) received distilled water and 99mTc-ECD; Infected group (I) received T. gondii strain and 99mTc-ECD; Infected and Treated group (IT), in addition to infection, received association of Pyrimethamine and Sulfadiazine and 99mTc-ECD. The T. gondii strain used in this study was TgCkRrRN3. Forty minutes after administration of the 99mTc-ECD, all animals were euthanized, and blood and brain samples were isolated. The counting of the radioactivity percentage per gram of tissue (%ATI/g) was calculated, and statistical analysis was performed by t-test, with a level of significance of p < .05.Results: There was a significant increase in %ATI/g between groups C and I on brain (0.35 ± 0.02 and 0.45 ± 0.04; p = .041) and on blood (0.80 ± 0.09 and 1.14 ± 0.31; p = .049). A significant decrease in %ATI/g occurred between groups C and IT on blood (0.80 ± 0.09 and 0.54 ± 0.08; p = .001) and on brain (0.35 ± 0.02 and 0.22 ± 0.04; p = .049).Conclusions: Combined therapy of anti-Toxoplasma drugs in infected mice reduced the uptake of 99mTc-ECD, probably due to its binding to plasma proteins.
Assuntos
Encéfalo/parasitologia , Encéfalo/efeitos da radiação , Cisteína/análogos & derivados , Compostos de Organotecnécio/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Toxoplasma , Toxoplasmose/tratamento farmacológico , Toxoplasmose/parasitologia , Animais , Antiprotozoários/uso terapêutico , Encéfalo/metabolismo , Cisteína/farmacocinética , Masculino , Camundongos , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Distribuição TecidualRESUMO
Toxoplasmosis in South America presents great health impacts and is a topic of research interest not only because of the severity of native cases but also due to the predominant atypical genotypes of the parasite circulating in this continent. Typically, symptomatic toxoplasmosis is treated with a combination of sulfadiazine (SDZ) and pyrimethamine (PYR). However, some clinical cases present treatment failures due to an inability of the drugs to control the infection or their significant adverse effects, which can lead to treatment interruption. Although resistance/susceptibility to the aforementioned drugs has been well described for clonal strains of Toxoplasma gondii spread to the Northern Hemisphere, less is known about the South American atypical strains. In this study, the effectiveness of SDZ and PYR for the treatment of mice during acute infection with different atypical T. gondii strains was evaluated. Swiss mice were infected with seven T. gondii strains obtained from newborn patients with congenital toxoplasmosis in Brazil. The infected mice were treated with 10-640â¯mg/kg per day of SDZ, 3-200â¯mg/kg per day of PYR, or a combination of both drugs with a lower dosage. The mice were evaluated for parameters including mortality, anti-T. gondii IgG production by ELISA and the presence of brain cysts. In addition, the presence of polymorphisms in the dhps gene was verified by gene sequencing. A descriptive analysis was used to assess the association between susceptibility to SDZ and/or PYR and the genotype. The TgCTBr4 and TgCTBr17 strains (genotype 108) presented lower susceptibility to SDZ or PYR treatment. The TgCTBr1 and TgCTBr25 strains (genotype 206) presented similar susceptibility to PYR but not SDZ treatment. The TgCTBr9 strain (genotype 11) was the only strain with high susceptibility to treatment with both drugs. The TgCTBr13 strain (genotype 208) was not susceptible to treatment with the lower PYR or SDZ doses. The TgCTBR23 strain (genotype 41) was more susceptible to PYR than to SDZ treatment. However, the association of low SDZ and PYR doses showed good efficacy for the treatment of experimental toxoplasmosis with T. gondii atypical strains obtained from newborns in Brazil. A new mutation in the T. gondii dhps gene (I347M) was identified that might be associated with the SDZ low sensitivity profile observed for the TgCTBr4 and TgCTBr17 isolates.
Assuntos
Antiprotozoários/uso terapêutico , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasmose Animal/tratamento farmacológico , Toxoplasmose Congênita/parasitologia , Álcool Desidrogenase/genética , Animais , Antiprotozoários/farmacologia , Feminino , Genótipo , Humanos , Recém-Nascido , Camundongos , Pirimetamina/farmacologia , Sulfadiazina/farmacologia , Toxoplasma/classificação , Toxoplasma/efeitos dos fármacos , Toxoplasma/genética , Toxoplasma/patogenicidade , Toxoplasmose Animal/parasitologia , Toxoplasmose Congênita/tratamento farmacológico , VirulênciaRESUMO
There are no standard guidelines for the treatment of cryptosporidiosis in reptiles. The aim of this study was to evaluate the efficacy of two cryptosporidiosis therapies in captive green iguanas. Eight green iguanas aged 2-6 years, including 6 (1 â and 5 â) animals with chronic diarrhea, received treatment for cryptosporidiosis. The presence of Cryptosporidium sp. oocysts was determined in 8 iguanas (100%), Isospora sp. oocysts were detected in 3 animals (37.5%), and Oxyuridae eggs were observed in 5 iguanas (62.5%). The animals were divided into two therapeutic groups (A and B). Group A iguanas were administered halofuginone (Halocur, 0,50â¯mg/ml Intervet Productions S.A., France) at a dose of 110â¯mg/kg body weight (BW) every 7â¯days for 5 weeks. Group B animals were administered sulfadiazine and trimethoprim (Norodine Vet Oral Paste sulfadiazine 288,3â¯mg/g, trimethoprim 58â¯mg/g, ScanVet Animal Health A/S, Denmark) at 75â¯mg/kg BW per os every 5â¯days for 5 weeks and spiramycin and metronidazole (Stomorgyl, spiramycin 1500000 IU, metronidazole 250â¯mg, Merial, France) at 200â¯mg/kg BW every 5â¯days for 5 weeks. Both groups received hyperimmune bovine colostrum and subcutaneous fluids. Before treatment, the average number of Cryptosporidium sp. oocysts in 1â¯g of feces was determined at 1.71â¯*â¯105 (±313,262.44) in group A and 1.56â¯*â¯105 (±262,908.53) in group B; the average number of Isospora sp. oocysts was determined at 3.53â¯*â¯103 (±1747.38), and the average number of Oxyuridae eggs was determined at 810 (±496.74). Blood tests were performed once before treatment. The results of blood morphology and biochemistry tests before treatment revealed leukocytosis with a significant increase in heterophile and monocyte counts in all animals. Dehydration, elevated hematocrit values and low levels of Na+, Ca2+, PO4- and Cl- ions were observed in 6 iguanas. Two iguanas died during treatment. The gross necropsy revealed acute inflammation of gastric and duodenal mucosa, mucosal ecchymoses in the gastrointestinal tract, hepatomegaly and liver congestion, cholecystitis, enlarged kidneys and renal edema and congestion, cystitis, and an absence of fat bodies. Parasites were not detected in any developmental form after 40â¯days of therapy and during an monthly 18-month follow-up period. Effective treatment of cryptosporidiosis in reptiles minimizes the adverse consequences of disease, improves the animals' well-being and decreases euthanasia rates.
Assuntos
Coccidiostáticos/administração & dosagem , Coccidiostáticos/uso terapêutico , Criptosporidiose/tratamento farmacológico , Cryptosporidium/efeitos dos fármacos , Iguanas/parasitologia , Animais , Coccidiostáticos/efeitos adversos , Criptosporidiose/sangue , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Cryptosporidium/isolamento & purificação , Fezes/parasitologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/parasitologia , Oocistos/efeitos dos fármacos , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Polônia/epidemiologia , Quinazolinonas/administração & dosagem , Quinazolinonas/efeitos adversos , Quinazolinonas/uso terapêutico , Sulfadiazina/administração & dosagem , Sulfadiazina/efeitos adversos , Sulfadiazina/uso terapêutico , Resultado do Tratamento , Trimetoprima/administração & dosagem , Trimetoprima/efeitos adversos , Trimetoprima/uso terapêuticoRESUMO
PURPOSE: To describe treatment practices for ocular toxoplasmosis among members of the Brazilian Uveitis Society. METHODS: An online questionnaire sent to specialists, between October 2014 and March 2015. RESULTS: Most respondents (67.9%) treat all active cases. Most specialists consider visual acuity <20/200 (88.2%), severe vitreous inflammation (94.1%), and ocular disease during acquired infection (88.2%) as absolute indications for treatment. Systemic steroids are associated with anti-toxoplasmic therapy in most cases by 50.9% of the respondents. For immunocompetent individuals, 57.4% of the respondents chose trimethoprim/sulfamethoxazole. Classical therapy (sulfadiazine/pyrimethamine) is preferred most for patients with central lesions (70.4%), immunosuppression (68.4%), acquired infection (70.4%), and atypical forms (74.1%). For patients with frequent relapses, 84.9% of the respondents preferred antibiotic prophylaxis. CONCLUSIONS: Treatment patterns of ocular toxoplasmosis are not uniform among Brazilian specialists. Most specialists treat all cases of active retinochoroiditis. Typical cases are more frequently treated with trimethoprim/sulfamethoxazole. However, classical therapy is the regimen of choice when lesions are considered more severe.
Assuntos
Padrões de Prática Médica/estatística & dados numéricos , Toxoplasmose Ocular/tratamento farmacológico , Antibacterianos/uso terapêutico , Brasil , Glucocorticoides/uso terapêutico , Inquéritos Epidemiológicos , Humanos , Oftalmologia , Pirimetamina/uso terapêutico , Especialização , Sulfadiazina/uso terapêutico , Inquéritos e Questionários , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoAssuntos
Toxoplasma/patogenicidade , Toxoplasmose Congênita/diagnóstico por imagem , Antiprotozoários/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/parasitologia , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Calcinose/parasitologia , Feminino , Humanos , Lactente , Leucovorina/uso terapêutico , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Tomógrafos Computadorizados , Toxoplasmose Congênita/imunologiaRESUMO
BACKGROUND: There are few studies reporting frequency and control of adverse events associated with congenital toxoplasmosis treatment. The objective of this study is to describe treatment adherence and adverse hematologic events in a cohort of children identified with congenital toxoplasmosis in Minas Gerais, Brazil. METHODS: Children were treated with sulfadiazine, pyrimethamine and folinic acid and were evaluated clinically and by laboratory tests at regular intervals. RESULTS: Of 146,307 live newborns who participated in the Neonatal Screening Program in Minas Gerais in 2006-2007, 190 had congenital toxoplasmosis. Among the 171 children whose treatment data were available, 73.1% completely adhered to antiparasitic therapy. Hematologic adverse events (macrocytic anemia and/or neutropenia and/or thrombocytopenia) were diagnosed in 44% of them. The most common adverse event was neutropenia (31%). In most cases, it was not severe and reversed after increase in folinic acid dosage (25.7%) or temporary treatment suspension (1.8%). No infections were observed in association with neutropenic events. Significant associations were detected between macrocytic anemia and lower weight Z score at first medical appointment (P = 0.03), and between severe neutropenia (<500/mm) and lower weight Z score toward the end of treatment (P = 0.04). CONCLUSIONS: The high frequency of hematologic adverse events found, especially in malnourished children, highlight the importance of careful monitoring of these children throughout treatment, as well as considering nutritional aspects and the need for higher doses of folinic acid. With adequate monitoring, antiparasitic treatment was feasible and relatively safe in the setting of this large screening program for congenital toxoplasmosis.
Assuntos
Antiprotozoários/efeitos adversos , Medula Óssea , Neutropenia/induzido quimicamente , Toxoplasmose Congênita/tratamento farmacológico , Toxoplasmose Congênita/epidemiologia , Antiprotozoários/uso terapêutico , Medula Óssea/efeitos dos fármacos , Medula Óssea/fisiopatologia , Brasil/epidemiologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Triagem Neonatal , Neutropenia/diagnóstico , Neutropenia/epidemiologia , Estudos Prospectivos , Pirimetamina/efeitos adversos , Pirimetamina/uso terapêutico , Sulfadiazina/efeitos adversos , Sulfadiazina/uso terapêutico , Toxoplasmose Congênita/complicaçõesRESUMO
Toxoplasmic encephalitis is a rare infectious complication in patients with hematological malignancy except for allogeneic hematopoietic stem cell transplantation (HSCT). We herein report a case of possible toxoplasmic encephalitis with untreated hairy cell leukemia variant. Magnetic resonance imaging showed multiple nodules with surrounding edema in the entire cerebrum. A polymerase chain reaction analysis for Toxoplasma gondii was negative. Her signs and symptoms fully recovered by empirical therapy with sulfadiazine and pyrimethamine. Toxoplasmic encephalitis may occur in patients who undergo non-allogeneic HSCT for hematological malignancies, even in those who have not been treated.
Assuntos
Encefalite Infecciosa/diagnóstico , Leucemia de Células Pilosas/diagnóstico , Toxoplasmose Cerebral/diagnóstico , Idoso , Animais , Antiprotozoários/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Hemiplegia/etiologia , Humanos , Encefalite Infecciosa/complicações , Encefalite Infecciosa/diagnóstico por imagem , Encefalite Infecciosa/tratamento farmacológico , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/diagnóstico por imagem , Leucemia de Células Pilosas/tratamento farmacológico , Imageamento por Ressonância Magnética , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/complicações , Toxoplasmose Cerebral/diagnóstico por imagem , Toxoplasmose Cerebral/tratamento farmacológicoRESUMO
Staphylococcus aureus is an important human and veterinary pathogen that causes economic loss in the poultry industry. This study aimed to compare therapeutic efficacy of 4 commonly used antibiotics in poultry on S. aureus-induced arthritis in broilers. Sixty broilers, 8 weeks of age, were assigned at random into 7 groups as follows: (1) negative control (n = 5); (2) vehicle control (n = 5); (3) sulfadiazine-trimethoprim, 250 ml/1000 l drinking water (n = 10); (4) oxytetracycline 20%, 1 mg/l drinking water (n = 10); (5) florfenicol 10%, 1/1000 v/v in drinking water (n = 10); (6) enrofloxacin 10%, 1/1000 v/v in drinking water (n = 10) and (7) positive control (n = 10). Birds in group 2 were injected with 1 ml of sterile TSB medium into the right tibiotarsal joint on d 0 while other birds (except group 1) were challenged with 1 ml of 1.2 × 10(10) CFU/ml suspension of S. aureus bacteria. Antibiotic therapy was started from d 4 post challenge and continued for 5 d. At the end, birds were weighed and clinical severity of arthritis was determined. After blood collection, birds were slaughtered and tibiotarsal and hip joints were evaluated grossly. The content of inflammatory exudates of tibiotarsal joint and the degree of femoral head necrosis were recorded. Mucin clot test and histopathological evaluation were performed on right tibiotarsal joint. Serum interleukin 6 was also assayed. Sulfadiazine-trimethoprim had higher therapeutic efficiency with regard to most of the assayed criteria, whereas none of the antibiotics significantly affected femoral head necrosis and body weight. These data will help clinicians to have better antibiotic choice in field conditions.
Assuntos
Antibacterianos/uso terapêutico , Artrite/veterinária , Galinhas , Doenças das Aves Domésticas/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Animais , Antibacterianos/farmacologia , Artrite/tratamento farmacológico , Artrite/microbiologia , Combinação de Medicamentos , Enrofloxacina , Feminino , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Masculino , Oxitetraciclina/farmacologia , Oxitetraciclina/uso terapêutico , Doenças das Aves Domésticas/microbiologia , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Sulfadiazina/farmacologia , Sulfadiazina/uso terapêutico , Tianfenicol/análogos & derivados , Tianfenicol/farmacologia , Tianfenicol/uso terapêutico , Resultado do Tratamento , Trimetoprima/farmacologia , Trimetoprima/uso terapêuticoRESUMO
The current work was undertaken to investigate the potential effectiveness of Thymus vulgaris ethanolic extract (TVE) against Toxoplasma gondii infection in chronic experimental toxoplasmosis. To evaluate prophylactic effects, mice received 500 mg/kg TVE for 5 days before they were infected by an avirulent Me49 T. gondii strain. To investigate the therapeutic effects of the extract postinfection, daily treatment with TVE was initiated at 6 weeks postinfection and continued for 10 days. The following groups of animals were used as controls: uninfected/non-treated, infected/non-treated, and infected/treated with a combination of pyrimethamine and sulfadiazine. Brain cyst count and histopathological changes using H&E and Feulgen stains were used to evaluate the efficacy of TVE. The mean number of brain cysts was significantly decreased by 24 % in mice treated prophylactically with TVE. TVE also significantly reduced the mean number of brain cysts when administered to animals already chronically infected with T. gondii. The effect of TVE was comparable to that of treatment with a mixture of sulfadiazine and pyrimethamine (46 and 51 % reduction, respectively). Moreover, considerable amelioration of the pathological lesions in the brain and retina was observed. The results demonstrate the potential efficacy of T. vulgaris as a new natural therapeutic and prophylactic agent for use in the treatment of chronic toxoplasmosis.
Assuntos
Extratos Vegetais/farmacologia , Thymus (Planta)/química , Toxoplasma/efeitos dos fármacos , Toxoplasmose/tratamento farmacológico , Animais , Encéfalo/parasitologia , Encéfalo/patologia , Doença Crônica , Modelos Animais de Doenças , Etanol , Humanos , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Pirimetamina/farmacologia , Pirimetamina/uso terapêutico , Sulfadiazina/farmacologia , Sulfadiazina/uso terapêutico , Toxoplasmose/parasitologia , Toxoplasmose/patologiaRESUMO
Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available drugs that have shown efficacy in disease models but which lack clinical case reports. Ideally, less-toxic treatments for the acute disease can be identified and developed, with an additional goal of cyst clearance from human and animal hosts.
Assuntos
Antiprotozoários/uso terapêutico , Reposicionamento de Medicamentos , Toxoplasma/efeitos dos fármacos , Toxoplasmose/tratamento farmacológico , Animais , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Antipsicóticos/uso terapêutico , Atovaquona/uso terapêutico , Clindamicina/uso terapêutico , Humanos , Macrolídeos/uso terapêutico , Testes de Sensibilidade Parasitária , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasma/patogenicidade , Toxoplasma/fisiologia , Toxoplasmose/parasitologia , Toxoplasmose/patologiaRESUMO
Objetivo: Describir una forma de presentación atípica de toxoplasmosis ocular, enfatizando la importancia de la jerarquización de los hallazgos clínicos y las limitaciones de la serología para realizar un diagnóstico temprano. Pacientes y Métodos: Estudio retrospectivo y descriptivo de tres casos clínicos de toxoplasmosis ocular activa, con presentación atípica (compromiso del nervio óptico), derivados al Servicio de Oftalmología del Hospital J. P. Garrahan en el periodo comprendido entre 2007 y 2010. Resultados: En los tres casos presentados la sospecha clínica de toxoplasmosis ocular no se correlacionó con evidencia serológica de infección reciente. En un caso, la terapéutica específica temprana, basada en la sospecha clínica, resultó en una excelente recuperación funcional. Un tratamiento tardío puede interferir en el resultado visual. Conclusiones: Basados en los hallazgos clínicos y la alta sospecha de esta patología debe iniciarse el tratamiento específico sin esperar que los resultados serológicos la confirmen. Eventualmente, la mejoría clínica confirmara el diagnóstico. El comportamiento de los títulos de anticuerpos en el curso de la enfermedad ocular no siempre es confiable, y en muchos casos retrasa el comienzo de la terapéutica con la consiguiente mala rehabilitación visual de estos pacientes (AU)
Objective: To describe an atypical presentation of ocular toxoplasmosis, emphasizing the importance of clinical findings and the limitations of serology in the early diagnosis. Patients and Methods: A retrospective, descriptive study was conducted of three cases with active ocular toxoplasmosis with an atypical presentation (optic nerve involvement), referred to the Department of Ophthalmology of Hospital J. P. Garrahan between 2007 and 2010. Results: In the three cases presented here clinical suspicion of ocular toxoplasmosis did not correlate with serological evidence of a recent infection. In one case, early treatment, based on clinical suspicion, resulted in excellent functional recovery. Late management may compromise visual outcome. Conclusions: Based on clinical findings and suspicion of the pathology, specific treatment should be started without waiting for serological confirmation. Eventually, clinical improvement will confirm the diagnosis. The behavior of antibody titres in the course of the ocular disease is not always reliable and often delays treatment initiation with subsequent difficulties in the visual rehabilitation of these patients (AU)
Assuntos
Humanos , Criança , Inflamação/parasitologia , Metilprednisolona/uso terapêutico , Doenças do Nervo Óptico/parasitologia , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/tratamento farmacológico , Pirimetamina/uso terapêutico , Estudos Retrospectivos , Sulfadiazina/uso terapêuticoRESUMO
Toxoplasmic encephalitis represents a rare, but often fatal infection after allogeneic hematopoietic stem cell transplantation. Polymerase chain reaction (PCR)-based preemptive therapy is considered promising for this disease, but is not routinely applied, especially in low seroprevalence countries including Japan. We encountered 2 cases of toxoplasmic encephalitis after transplantation that were successfully treated. The diagnosis of toxoplasmic encephalitis in these cases was confirmed by PCR testing when neurological symptoms were observed. Both patients received pyrimethamine and sulfadiazine treatments within 2 weeks of the development of neurological symptoms, and remained free of recurrence for 32 and 12 months. These results emphasized the importance of the PCR test and immediate treatment after diagnosis for the management of toxoplasmic encephalitis.
Assuntos
Antiprotozoários/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Encefalite Infecciosa/tratamento farmacológico , Infecções Oportunistas/tratamento farmacológico , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasmose Cerebral/tratamento farmacológico , Adulto , Quimioterapia Combinada , Diagnóstico Precoce , Humanos , Encefalite Infecciosa/complicações , Encefalite Infecciosa/diagnóstico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Masculino , Infecções Oportunistas/complicações , Infecções Oportunistas/diagnóstico , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Toxoplasmose Cerebral/complicações , Toxoplasmose Cerebral/diagnóstico , Transplante HomólogoRESUMO
BACKGROUND: Although Toxoplasma gondii infection is normally asymptomatic, severe cases of toxoplasmosis may occur in immunosuppressed patients or congenitally infected newborns. When a fetal infection is established, the recommended treatment is a combination of pyrimethamine, sulfadiazine and folinic acid (PSA). The aim of the present study was to evaluate the efficacy of azithromycin to control T. gondii infection in human villous explants. METHODS: Cultures of third trimester human villous explants were infected with T. gondii and simultaneously treated with either PSA or azithromycin. Proliferation of T. gondii, as well as production of cytokines and hormones by chorionic villous explants, was analyzed. RESULTS: Treatment with either azithromycin or PSA was able to control T. gondii infection in villous explants. After azithromycin or PSA treatment, TNF-α, IL-17A or TGF-ß1 levels secreted by infected villous explants did not present significant differences. However, PSA-treated villous explants had decreased levels of IL-10 and increased IL-12 levels, while treatment with azithromycin increased production of IL-6. Additionally, T. gondii-infected villous explants increased secretion of estradiol, progesterone and HCG+ß, while treatments with azithromycin or PSA reduced secretion of these hormones concurrently with decrease of parasite load. CONCLUSIONS: In conclusion, these results suggest that azithromycin may be defined as an effective alternative drug to control T. gondii infection at the fetal-maternal interface.
Assuntos
Azitromicina/uso terapêutico , Vilosidades Coriônicas/parasitologia , Toxoplasmose/tratamento farmacológico , Azitromicina/farmacologia , Feminino , Humanos , Técnicas In Vitro , Leucovorina/administração & dosagem , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Gravidez , Pirimetamina/administração & dosagem , Pirimetamina/farmacologia , Pirimetamina/uso terapêutico , Sulfadiazina/administração & dosagem , Sulfadiazina/farmacologia , Sulfadiazina/uso terapêutico , Toxoplasma/efeitos dos fármacosAssuntos
Toxoplasmose Cerebral/complicações , Macroglobulinemia de Waldenstrom/complicações , Idoso , Antiprotozoários/uso terapêutico , Biópsia , Infecção Hospitalar/complicações , Quimioterapia Combinada , Evolução Fatal , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Pneumonia/complicações , Ponte/parasitologia , Ponte/patologia , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/tratamento farmacológico , Toxoplasmose Cerebral/parasitologia , Macroglobulinemia de Waldenstrom/tratamento farmacológicoRESUMO
Question Congenital toxoplasmosis is a dangerous fetal infection. Why is routine screening for Toxoplasma gondii infection during pregnancy not available for most Canadians? Answer Low prevalence of the infection, high cost associated with testing, low sensitivity of screening tests, false-positive test results, and limitations of treatment effectiveness are all cited as reasons for not routinely screening for T gondii infection in Canada. Currently, screening for the detection of T gondii is only performed in Nunavik and other parts of northern Quebec owing to the high prevalence of infection in this region. Congenital toxoplasmosis causes neurologic or ocular disease (leading to blindness), as well as cardiac and cerebral anomalies.
Assuntos
Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Toxoplasmose/diagnóstico , Toxoplasmose/transmissão , Antibacterianos/uso terapêutico , Antiprotozoários/uso terapêutico , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Programas de Rastreamento , Gravidez , Pirimetamina/uso terapêutico , Espiramicina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasmose/tratamento farmacológico , Toxoplasmose Congênita/complicações , Toxoplasmose Congênita/prevenção & controleRESUMO
Opportunistic infections cause a significant morbidity and mortality in immunocompromised patients. We describe the case of a patient with skin fusariosis and a probable cerebral toxoplasmosis after UCB stem cell transplantation for B-cell acute lymphoblastic leukaemia. Fusarium species (spp) infections are difficult to treat. To date, there has been no consensus on the treatment of fusariosis and the management of its side effects. Given the negative pretransplant Toxoplasma serology in this case, identifying the origin of the Toxoplasma infection was challenging. All usual transmission routes were screened for and ruled out. The patient's positive outcome was not consistent with that of the literature reporting 60% mortality due to each infection.