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Four cases of people living with HIV/AIDS (PLWHA) with calcified cerebral toxoplasmosis associated with perilesional edema causing a single episode of neurological manifestations have recently been reported. Here, we describe the first detailed description of perilesional edema associated with calcified cerebral toxoplasmosis causing three episodes of neurological manifestations in a PLWHA, including seizures in two of them. These recurrences occurred over approximately a decade. Throughout this period, the patient showed immunological and virological control of the HIV infection, while using antiretroviral therapy regularly. This case broadens the spectrum of an emerging presentation of calcified cerebral toxoplasmosis, mimicking a well-described finding of neurocysticercosis in immunocompetent hosts.
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Humanos , Calcinosis/complicaciones , Infecciones por VIH/complicaciones , Toxoplasmosis Cerebral/complicacionesRESUMEN
ABSTRACT Four cases of people living with HIV/AIDS (PLWHA) with calcified cerebral toxoplasmosis associated with perilesional edema causing a single episode of neurological manifestations have recently been reported. Here, we describe the first detailed description of perilesional edema associated with calcified cerebral toxoplasmosis causing three episodes of neurological manifestations in a PLWHA, including seizures in two of them. These recurrences occurred over approximately a decade. Throughout this period, the patient showed immunological and virological control of the HIV infection, while using antiretroviral therapy regularly. This case broadens the spectrum of an emerging presentation of calcified cerebral toxoplasmosis, mimicking a well-described finding of neurocysticercosis in immunocompetent hosts.
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Abstract Background Concomitant neurological diseases in people living with HIV/AIDS (PLWHA) is a challenging subject that has been insufficiently evaluated by prospective clinical studies. The goal of the present study was to identify the clinical characteristics and outcomes of PLWHA with cerebral toxoplasmosis and neurological co-infections. Methods We conducted a prospective observational cohort study at a tertiary teaching center in São Paulo, Brazil, from January to July 2017. Hospitalized PLWHA aged ≥ 18 years with cerebral toxoplasmosis were consecutively enrolled. A standardized neurological examination was performed at admission and weekly until discharge or death. Diagnosis and treatment followed institutional routines; neuroradiology, molecular diagnosis, neurosurgery, and the intensive care unit (ICU) were available. The main outcomes were neurological coinfections and in-hospital death. Results We included 44 (4.3%) cases among 1,032 hospitalized patients. The median age was 44 (interquartile range [IQR]: 35-50) years, and 50% (n = 22) of the patients were male. The median CD4+ T lymphocyte count was of 50 (IQR: 15-94) cells/mm3. Multiple lesions on computed tomography were present in 59% of the cases. Neurological coinfections were diagnosed in 20% (n = 9) of the cases, and cytomegalovirus was the most common etiology (encephalitis: n = 3; polyradiculopathy: n = 2). Longer hospital stays (30 versus 62 days; p= 0.021) and a higher rate of ICU admissions (14% versus 44%; p= 0.045) were observed among PLWHA with neurological coinfections in comparison to those without them. The rate of in-hospital mortality was of 13.6% (n = 6) (coinfection group: 33%; no coinfection group: 8.6%; p= 0.054). Conclusion Neurological c-infections were common among PLWHA with cerebral toxoplasmosis, and cytomegalovirus was the main copathogen. The group of PLWHA with neurological co-infections underwent longer hospital stays and more frequent intensive care unit admissions. Additionally, this group of patients tended to have higher in-hospital mortality rate.
Resumo Antecedentes Coinfecções neurológicas em pessoas que vivem com HIV/AIDS (PVHA) é um tema que não foi suficientemente avaliado em estudos clínicos prospectivos. Nosso objetivo foi identificar as características clínicas e os desfechos de PVHA com toxoplasmose cerebral e coinfecções neurológicas. Métodos Estudo prospectivo de coorte observacional conduzido em um centro de ensino terciário de São Paulo, Brasil, entre janeiro e julho de 2017. Foram incluídos consecutivamente PVHA internadas com ≥ 18 anos e toxoplasmose cerebral. Realizou-se exame neurológico padronizado na admissão e semanalmente até a alta/óbito. Tanto o diagnóstico quanto o tratamento seguiram a rotina institucional; neurorradiologia, diagnóstico molecular, neurocirurgia e Unidade de Terapia Intensiva (UTI) estavam disponíveis. Os principais desfechos foram coinfecções neurológicas e óbitos hospitalares. Resultados Incluímos 44 (4,3%) casos entre 1.032 pacientes internados. A idade mediana foi de 44 (intervalo interquartil [IIQ]: : 35-50) anos, e 50% (n = 22) dos pacientes eram do sexo masculino. A contagem mediana de linfócitos T CD4+ foi de 50 (IIQ:15-94) células/mm3. Múltiplas lesões na tomografia computadorizada foram observadas em 59% dos casos. Coinfecções neurológicas foram diagnosticadas em 20% (n = 9) dos casos, sendo o citomegalovírus a etiologia mais comum (encefalite: n = 3; polirradiculopatia: n = 2). Observou-se maior tempo de internação (26 versus 62 dias; p= 0,021) e uma taxa mais alta de admissão à UTI (14% versus 44%; p= 0,045) em PVHA com coinfecções neurológicas em comparação àquelas sem coinfecção. A mortalidade intra-hospitalar foi de 13,6% (n = 6) (grupo com coinfecções: 33% versus grupo sem coinfecção: 8,6%; p= 0,054). Conclusão Coinfecções neurológicas foram comuns em PVHA com toxoplasmose cerebral, sendo o citomegalovírus o principal copatógeno. O grupo de PVHA com coinfecções neurológicas apresentou maior tempo de internação, maior taxa de internações na UTI, e tendência a maior taxa de mortalidade intra-hospitalar.
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Introducción: El síndrome de inmunodeficiencia adquirida es el estadio final de una enfermedad crónica, transmisible y progresiva de causa viral. La neurotoxoplasmosis es la infección oportunista más frecuente en pacientes inmunodeprimidos. Objetivo: Caracterizar a los pacientes con neurotoxoplasmosis secundaria al virus de inmunodeficiencia humana/sida según variables epidemiológicas, clínicas e imagenológicas. Métodos: Se efectuó un estudio observacional, descriptivo y transversal de 18 pacientes con sida, quienes recibieron diagnóstico clínico y microbiológico de neurotoxoplasmosis, caracterizados según hallazgos en la resonancia magnética por imágenes antes y después del tratamiento, desde enero de 2017 hasta diciembre de 2019. Resultados: En la investigación primaron el sexo masculino, las edades de 34 o menos años (66,7 %) y las manifestaciones clínicas de fiebre (100,0 %) y cefalea (88,9 %). La localización más habitual de las lesiones fue en la unión cortico-subcortical (66,1 %). Resultaron más frecuentes las imágenes hipointensas en T1 y en recuperación de la inversión atenuada de fluido y las imágenes hiperintensas en T2; se destacaron las lesiones múltiples (66,7 %), de pequeño tamaño (50,0 %) y los contornos irregulares (88,9 %). Antes del tratamiento tuvieron mayor frecuencia el realce de tipo anular (72,2 %) y el edema vasogénico de grado 2 (50,0 %); después de este, 55,6 % de los afectados presentaron calcificaciones y 72,2 % hemorragia intralesional. Se evidenció que 77,8 % tuvieron mejoría con respecto al edema cerebral. Conclusiones: La resonancia magnética por imágenes permitió caracterizar a los pacientes con virus de inmunodeficiencia humana/sida y toxoplasmosis cerebral, así como evaluar la respuesta terapéutica a través de las modificaciones en los hallazgos imagenológicos.
Introduction: The acquired immunodeficiency syndrome is the final stage of a chronic, communicable and progressive disease of viral cause. The neurotoxoplasmosis is the most frequent opportunist infection in immunodepressed patients. Objective: To characterize patients with secondary neurotoxoplasmosis to human immunodeficiency virus/aids according to epidemiological, clinical and imaging variables. Methods: An observational, descriptive and cross-sectional study of 18 patients with AIDS was carried out, who received clinical and microbiological diagnosis of neurotoxoplasmosis, characterized according to findings in the magnetic resonance by images before and after the treatment, from January, 2017 to December, 2019. Results: In the investigation there was a prevalence of the male sex, the ages of 34 or less years (66.7 %) and the clinical signs of fever (100.0 %) and headache (88.9 %). The most common localization of the lesions was in the cortico-subcortical juntion (66.1 %). The hypointense images in T1 and fluid attenuated inversion recovery and hyperintense images in T2 were the most frequent; the multiple lesions (66.7 %) of small size (50.0 %) and irregular contours (88.9 %) were notable. Before the treatment the enhance of anular type had more frequency (72.2 %) and grade 2 vasogenic edema (50.0 %); after this, 55.6 % of those affected persons presented calcifications and 72.2 % intralesional hemorrhages. It was evidenced that 77.8 % had improvement respect the cerebral edema. Conclusions: The magnetic resonance by images allowed to characterize the patients with human immunodeficiency virus/aids and cerebral toxoplasmosis, as well as to evaluate the therapeutic response through the modifications in the imaging findings.
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Síndrome de Inmunodeficiencia Adquirida , Toxoplasmosis Cerebral , Infecciones Oportunistas , Espectroscopía de Resonancia MagnéticaRESUMEN
Toxoplasma gondii (T. gondii) is the causal agent of toxoplasmosis, which produces damage in the central nervous system (CNS). Toxoplasma-CNS interaction is critical for the development of disease symptoms. T. gondii can form cysts in the CNS; however, neurons are more resistant to this infection than astrocytes. The probable mechanism for neuron resistance is a permanent state of neurons in the interface, avoiding the replication of intracellular parasites. Steroids regulate the formation of Toxoplasma cysts in mice brains. 17ß-estradiol and progesterone also participate in the control of Toxoplasma infection in glial cells in vitro. The aim of this study was to evaluate the effects of 17ß-estradiol, progesterone, and their specific agonists-antagonists on Toxoplasma infection in neurons in vitro. Neurons cultured were pretreated for 48 h with 17ß-estradiol or progesterone at 10, 20, 40, 80, or 160 nM/mL or tamoxifen 1 µM/mL plus 17ß-estradiol at 10, 20, 40, 80, and 160 nM/mL. In other conditions, the neurons were pretreated during 48 h with 4,4',4â³-(4-propyl-[1H] pyrozole-1,3,5-triyl) trisphenol or 23-bis(4-hydroxyphenyl) propionitrile at 1 nM/mL, and mifepristone 1 µM/mL plus progesterone at 10, 20, 40, 80, and 160 nM/mL. Neurons were infected with 5000 tachyzoites of the T. gondii strain RH. The effect of 17ß estradiol, progesterone, their agonists, or antagonists on Toxoplasma infection in neurons was evaluated at 24 and 48 h by immunocytochemistry. T. gondii replication was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. 17ß-Estradiol alone or plus tamoxifen reduced infected neurons (50%) compared to the control at 48 h. Progesterone plus estradiol decreased the number of intracellular parasites at 48 h of treatment compared to the control (p < 0.001). 4,4',4â³-(4-propyl-[1H] pyrozole-1,3,5-triyl) trisphenol and 23-bis(4-hydroxyphenyl) propionitrile reduced infected neurons at 48 h of treatment significantly compared to the control (p < 0.05 and p < 0.001, respectively). The Toxoplasma infection process was decreased by the effect of 17ß-estradiol alone or combined with tamoxifen or progesterone in neurons in vitro. These results suggest the essential participation of progesterone and estradiol and their classical receptors in the regulation of T. gondii neuron infection.
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INTRODUCCIÓN: La toxoplasmosis congénita continúa siendo un problema de salud pública. Aun cuando existen guías plenamente divulgadas y conocidas, se observa poca implementación de ellas en algunas instituciones de salud y una inadecuada interpretación de las pruebas serológicas en las gestantes. Esto puede generar falta de captación y tratamiento en embarazadas con primoinfección por Toxoplasma gondii. CASOS CLÍNICOS: Se reportan dos casos de toxoplasmosis congénita, uno de ellos con desenlace fatal. En ambos no se siguieron las guías de práctica clínica, lo cual conllevó un diagnóstico tardío y, en consecuencia, un manejo en condiciones inapropiadas con daños graves. CONCLUSIONES: La toxoplasmosis es una infección congénita aún prevalente en algunos países, con secuelas graves, discapacidad neurológica y riesgo de daño ocular, incluso tardío. Además, existen algunas variedades de cepas de T. gondii con un comportamiento más agresivo en Latinoamérica, lo cual empeora la presentación de los casos e incluye mayor riesgo de muerte. BACKGROUND: Congenital toxoplasmosis continues to be a public health problem. Although clinical guidelines have been divulgated and are well known, they are not implemented in some health institutions, in addition of an inappropriate interpretation of the serological tests in pregnant women. This situation can lead to lack of screening and treatment in pregnant women with primary Toxoplasma gondii infection. CASE REPORTS: We report two cases of congenital toxoplasmosis, one with a fatal outcome. In both cases, the clinical guidelines were not initially followed, leading to a delayed diagnosis and, consequently, an inappropriate management in conditions with severe damage. CONCLUSIONS: Toxoplasmosis is a congenital infection still prevalent in some countries, with severe sequelae, neurological disability, and even late risk of ocular damage. Additionally, some varieties of the T. gondii strains have a more aggressive pattern in Latin America, worsening the clinical presentation of cases and including a high risk of death.
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Toxoplasmosis Congénita , Colombia , Femenino , Humanos , Embarazo , Toxoplasmosis Congénita/diagnóstico , Toxoplasmosis Congénita/tratamiento farmacológicoRESUMEN
Resumen Introducción: La toxoplasmosis congénita continúa siendo un problema de salud pública. Aun cuando existen guías plenamente divulgadas y conocidas, se observa poca implementación de ellas en algunas instituciones de salud y una inadecuada interpretación de las pruebas serológicas en las gestantes. Esto puede generar falta de captación y tratamiento en embarazadas con primoinfección por Toxoplasma gondii. Casos clínicos: Se reportan dos casos de toxoplasmosis congénita, uno de ellos con desenlace fatal. En ambos no se siguieron las guías de práctica clínica, lo cual conllevó un diagnóstico tardío y, en consecuencia, un manejo en condiciones inapropiadas con daños graves. Conclusiones: La toxoplasmosis es una infección congénita aún prevalente en algunos países, con secuelas graves, discapacidad neurológica y riesgo de daño ocular, incluso tardío. Además, existen algunas variedades de cepas de T. gondii con un comportamiento más agresivo en Latinoamérica, lo cual empeora la presentación de los casos e incluye mayor riesgo de muerte.
Abstract Background: Congenital toxoplasmosis continues to be a public health problem. Although clinical guidelines have been divulgated and are well known, they are not implemented in some health institutions, in addition of an inappropriate interpretation of the serological tests in pregnant women. This situation can lead to lack of screening and treatment in pregnant women with primary Toxoplasma gondii infection. Case reports: We report two cases of congenital toxoplasmosis, one with a fatal outcome. In both cases, the clinical guidelines were not initially followed, leading to a delayed diagnosis and, consequently, an inappropriate management in conditions with severe damage. Conclusions: Toxoplasmosis is a congenital infection still prevalent in some countries, with severe sequelae, neurological disability, and even late risk of ocular damage. Additionally, some varieties of the T. gondii strains have a more aggressive pattern in Latin America, worsening the clinical presentation of cases and including a high risk of death.
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Resumen Se reporta el caso de un paciente masculino de 29 años con antecedente de diabetes mellitus tipo 1, con enfermedad renal crónica estadio 5 secundaria a enfermedad renal diabética que requirió de trasplante renal de donante vivo en el año 2000 y en tratamiento inmunosupresor con prednisolona, tacrolimus y micofenolato desde dicho procedimiento, quien ingresó al servicio de urgencias por crisis epiléptica focal con generalización secundaria. El enfoque diagnóstico de toxoplasmosis cerebral en pacientes inmunocomprometidos es un reto clínico debido a la gran variabilidad de signos y síntomas asociados en esta población y a la alta frecuencia de complicaciones, lo cual puede confundir el diagnostico.
Abstract A 29-year-old male patient with a history of type 1 diabetes mellitus, stage 5 chronic kidney disease secondary to diabetic kidney disease that required living donor kidney transplantation in 2000. During these years, he has received immunosuppressive treatment with prednisolone, tacrolimus, and mycophenolate. He was admitted to the emergency department for focal epileptic crisis with secondary generalization. The diagnostic approach of cerebral toxoplasmosis in immunocompromised patients is a clinical challenge, due to the great variability of associated signs and symptoms in this population and the high frequency of complications, which can confuse the diagnosis.
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Toxoplasma gondii infection can trigger autoreactivity by different mechanisms. In the case of ocular toxoplasmosis, disruption of the blood-retinal barrier may cause exposure of confined retinal antigens such as recoverin. Besides, cross-reactivity can be induced by molecular mimicry of parasite antigens like HSP70, which shares 76% identity with the human ortholog. Autoreactivity can be a determining factor of clinical manifestations in the eye and in the central nervous system. We performed a prospective observational study to determine the presence of autoantibodies against recoverin and HSP70 by indirect ELISA in the serum of 65 patients with ocular, neuro-ophthalmic and congenital cerebral toxoplasmosis. We found systemic autoantibodies against recoverin and HSP70 in 33.8% and 15.6% of individuals, respectively. The presence of autoantibodies in cases of OT may be related to the severity of clinical manifestations, while in cases with CNS involvement they may have a protective role. Unexpectedly, anti-recoverin antibodies were found in patients with cerebral involvement, without ocular toxoplasmosis; therefore, we analyzed and proved cross-reactivity between recoverin and a brain antigen, hippocalcin, so the immunological phenomenon occurring in one immune-privileged organ (e.g. the central nervous system) could affect the environment of another (egg. the eye).
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Autoanticuerpos/inmunología , Autoantígenos/inmunología , Interacciones Huésped-Parásitos/inmunología , Toxoplasmosis Cerebral/inmunología , Toxoplasmosis Congénita/inmunología , Toxoplasmosis Ocular/inmunología , Adolescente , Adulto , Secuencia de Aminoácidos , Antígenos de Protozoos/inmunología , Niño , Preescolar , Reacciones Cruzadas/inmunología , Femenino , Proteínas HSP70 de Choque Térmico/química , Proteínas HSP70 de Choque Térmico/inmunología , Hipocalcina/química , Hipocalcina/inmunología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Recoverina/química , Recoverina/inmunología , Toxoplasma/inmunología , Toxoplasmosis Cerebral/diagnóstico , Toxoplasmosis Cerebral/parasitología , Toxoplasmosis Congénita/diagnóstico , Toxoplasmosis Congénita/parasitología , Toxoplasmosis Ocular/diagnóstico , Toxoplasmosis Ocular/parasitología , Adulto JovenRESUMEN
The incidence of infectious diseases affecting the central nervous system (CNS) has been increasing over the last several years. Among the reasons for the expansion of these diseases and the appearance of new neuropathogens are globalization, global warming, and the increased proximity between humans and wild animals due to human activities such as deforestation. Neurotropism affecting normal brain function is shared by organisms such as viruses, bacteria, fungi, and parasites. Neuroinfections caused by these agents activate immune responses, inducing neuroinflammation, excitotoxicity, and neurodegeneration. Purinergic signaling is an evolutionarily conserved signaling pathway associated with these neuropathologies. During neuroinfections, host cells release ATP as an extracellular danger signal with pro-inflammatory activities. ATP is metabolized to its derivatives by ectonucleotidases such as CD39 and CD73; ATP and its metabolites modulate neuronal and immune mechanisms through P1 and P2 purinergic receptors that are involved in pathophysiological mechanisms of neuroinfections. In this review we discuss the beneficial or deleterious effects of various components of the purinergic signaling pathway in infectious diseases that affect the CNS, including human immunodeficiency virus (HIV-1) infection, herpes simplex virus type 1 (HSV-1) infection, bacterial meningitis, sepsis, cryptococcosis, toxoplasmosis, and malaria. We also provide a description of this signaling pathway in emerging viral infections with neurological implications such as Zika and SARS-CoV-2.
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Infecciones del Sistema Nervioso Central/metabolismo , Receptores Purinérgicos P1/metabolismo , Receptores Purinérgicos P2X/metabolismo , Receptores Purinérgicos P2Y/metabolismo , Complejo SIDA Demencia/metabolismo , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/metabolismo , Encefalitis por Herpes Simple/metabolismo , Humanos , Malaria/metabolismo , Meningitis Bacterianas/metabolismo , Meningitis Criptocócica/metabolismo , Pandemias , Neumonía Viral/metabolismo , SARS-CoV-2 , Sepsis/metabolismo , Transducción de Señal , Toxoplasmosis Cerebral/metabolismo , Infección por el Virus Zika/metabolismoAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Encéfalo/diagnóstico por imagen , Seropositividad para VIH/complicaciones , Meningitis/complicaciones , Toxoplasma/aislamiento & purificación , Toxoplasmosis Cerebral/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Adulto , Antiinfecciosos/uso terapéutico , Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Eosinófilos , Cefalea/etiología , Humanos , Meningitis/diagnóstico , Meningitis/tratamiento farmacológico , Náusea/etiología , Paresia/etiología , Reacción en Cadena de la Polimerasa , Sulfametoxazol/uso terapéutico , Tomografía Computarizada por Rayos X , Toxoplasma/genética , Toxoplasmosis Cerebral/líquido cefalorraquídeo , Toxoplasmosis Cerebral/complicaciones , Toxoplasmosis Cerebral/tratamiento farmacológico , Resultado del Tratamiento , Vómitos/etiologíaRESUMEN
This study investigated the potential of five miRNA candidates for cerebral toxoplasmosis/HIV co-infection (CT/HIV) biomarkers. miR-155-5p, miR-146a-5p, miR-21-5p, miR-125b-5p and miR-29c-3p were tested in 79 plasma divided into groups: 32 CT/HIV patients; 27 individuals with asymptomatic toxoplasmosis (AT); and 20 individuals seronegative for toxoplasmosis (NC). From each was collected peripheral blood/EDTA for laboratory diagnosis. Blood cells for DNA extractions (molecular diagnosis), plasma for RNA extractions (gene expression) and ELISA (serological diagnosis). miRNA expression was performed by qPCR, and values were expressed in Relative Quantification (RQ). Among the five miRNAs, miR-21-5p and miR-146a-5p were up-expressed in CT/HIV group when compared with AT and NC groups. RQ means for miR-21-5p and miR-146a-5p in CT/HIV group were 3.829 and 2.500, while in AT group, were 1.815 and 1.661, respectively. Differences between 3 groups were statistically significant (Kruskal-Wallis ANOVA test), as well as CT/HIV and AT groups (Mann-Whitney test). Plasma of CT/HIV and AT groups expressed similar levels of miR-29c-3p, miR-155-5p and miR-125b-5p. As NC group was different of CT/HIV and AT groups, differences between three groups were statistically significant (Kruskal-Wallis ANOVA test). No difference was shown between CT/HIV and AT groups (Mann-Whitney test). These results suggest the host miRNAs modulation by Toxoplasma gondii
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Humanos , Infecciones por VIH , Toxoplasmosis Cerebral , Infecciones Oportunistas Relacionadas con el SIDA , MicroARNsRESUMEN
This study investigated the potential of five miRNA candidates for cerebral toxoplasmosis/HIV co-infection (CT/HIV) biomarkers. miR-155-5p, miR-146a-5p, miR-21-5p, miR-125b-5p and miR-29c-3p were tested in 79 plasma divided into groups: 32 CT/HIV patients; 27 individuals with asymptomatic toxoplasmosis (AT); and 20 individuals seronegative for toxoplasmosis (NC). From each was collected peripheral blood/EDTA for laboratory diagnosis. Blood cells for DNA extractions (molecular diagnosis), plasma for RNA extractions (gene expression) and ELISA (serological diagnosis). miRNA expression was performed by qPCR, and values were expressed in Relative Quantification (RQ). Among the five miRNAs, miR-21-5p and miR-146a-5p were up-expressed in CT/HIV group when compared with AT and NC groups. RQ means for miR-21-5p and miR-146a-5p in CT/HIV group were 3.829 and 2.500, while in AT group, were 1.815 and 1.661, respectively. Differences between 3 groups were statistically significant (Kruskal-Wallis ANOVA test), as well as CT/HIV and AT groups (Mann-Whitney test). Plasma of CT/HIV and AT groups expressed similar levels of miR-29c-3p, miR-155-5p and miR-125b-5p. As NC group was different of CT/HIV and AT groups, differences between three groups were statistically significant (Kruskal-Wallis ANOVA test). No difference was shown between CT/HIV and AT groups (Mann-Whitney test). These results suggest the host miRNAs modulation by Toxoplasma gondii.
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Infecciones por VIH/sangre , MicroARNs/sangre , Toxoplasma , Toxoplasmosis Cerebral/sangre , Biomarcadores/sangre , Coinfección , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica , Infecciones por VIH/complicaciones , Humanos , Masculino , MicroARNs/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Toxoplasma/fisiología , Toxoplasmosis Cerebral/complicacionesRESUMEN
Cerebral toxoplasmosis is the most common cause of expansive brain lesions in people living with HIV/AIDS (PLWHA) and continues to cause high morbidity and mortality. The most frequent characteristics are focal subacute neurological deficits and ring-enhancing brain lesions in the basal ganglia, but the spectrum of clinical and neuroradiological manifestations is broad. Early initiation of antitoxoplasma therapy is an important feature of the diagnostic approach of expansive brain lesions in PLWHA. Pyrimethamine-based regimens and trimethoprim-sulfamethoxazole (TMP-SMX) seem to present similar efficacy, but TMP-SMX shows potential practical advantages. The immune reconstitution inflammatory syndrome is uncommon in cerebral toxoplasmosis, and we now have more effective, safe, and friendly combined antiretroviral therapy (cART) options. As a consequence of these 2 variables, the initiation of cART can be performed within 2 weeks after initiation of antitoxoplasma therapy. Herein, we will review historical and current concepts of epidemiology, diagnosis, and treatment of HIV-related cerebral toxoplasmosis
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VIH , Toxoplasmosis Cerebral , Infecciones Oportunistas Relacionadas con el SIDAAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antiinfecciosos/efectos adversos , Encéfalo/diagnóstico por imagen , Infecciones por VIH/complicaciones , Tomografía Computarizada por Rayos X/métodos , Toxoplasmosis Cerebral/tratamiento farmacológico , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Adulto , Anciano , Antiinfecciosos/uso terapéutico , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroimagen , Resultado del Tratamiento , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
Cerebral toxoplasmosis is the most common cause of expansive brain lesions in people living with HIV/AIDS (PLWHA) and continues to cause high morbidity and mortality. The most frequent characteristics are focal subacute neurological deficits and ring-enhancing brain lesions in the basal ganglia, but the spectrum of clinical and neuroradiological manifestations is broad. Early initiation of antitoxoplasma therapy is an important feature of the diagnostic approach of expansive brain lesions in PLWHA. Pyrimethamine-based regimens and trimethoprim-sulfamethoxazole (TMP-SMX) seem to present similar efficacy, but TMP-SMX shows potential practical advantages. The immune reconstitution inflammatory syndrome is uncommon in cerebral toxoplasmosis, and we now have more effective, safe, and friendly combined antiretroviral therapy (cART) options. As a consequence of these 2 variables, the initiation of cART can be performed within 2 weeks after initiation of antitoxoplasma therapy. Herein, we will review historical and current concepts of epidemiology, diagnosis, and treatment of HIV-related cerebral toxoplasmosis.
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Encéfalo/parasitología , Infecciones por VIH/complicaciones , Toxoplasmosis Cerebral/virología , Antirretrovirales/uso terapéutico , Antiprotozoarios/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/patología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/parasitología , Humanos , Síndrome Inflamatorio de Reconstitución Inmune , Toxoplasmosis Cerebral/diagnóstico , Toxoplasmosis Cerebral/tratamiento farmacológico , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
We report the case of a previously healthy 29-year-old man who has sex with men who was admitted with sub-acute onset of headache, seizures and altered mental status. Physical examination revealed oral thrush, mental confusion and right hemiparesis. An unenhanced computed tomography of the brain revealed multiple rounded hemorrhages associated with perilesional edema and no enhancement was seen after contrast infusion. A rapid test for HIV-1 was positive and the CD4 T-lymphocyte count was 120 cells/mm3. Pyrimethamine, sulfadiazine plus folinic acid and dexamethasome were started. After two weeks of treatment, the clinical condition and neuroimaging of the patient remained unaltered. A stereotactic brain biopsy was performed and the Histopathologic examination confirmed the diagnosis of hemorrhagic toxoplasmosis. After a longer course of anti-Toxoplasma treatment due to an incomplete clinical and radiological response, the patient was discharged home. Hemorrhagic toxoplasmosis is a rare presentation of cerebral toxoplasmosis and should be considered in the differential diagnosis of hemorrhagic cerebral lesions in HIV-infected patients in order to initiate specific treatment promptly