Calcified cerebral toxoplasmosis associated with recurrent perilesional edema causing neurological manifestations in an HIV-infected individual: case report with a decade-long follow-up

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.

Cerebral toxoplasmosis with neurological co-infection in people living with AIDS/HIV: results of a prospective cohort in São Paulo, Brazil / Toxoplasmose cerebral com coinfecção neurológica em pessoas que vivem com HIV/AIDS: resultados de uma coorte prospectiva em São Paulo, Brasil

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.

Cerebrospinal fluid inflammatory cytokine profiles of patients with neurotropic parasitic infections

@#The pathogenesis of chronic parasitic central nervous system (CNS) infections, including granulomatous amoebic meningoencephalitis (GAE), cerebral toxoplasmosis (CT), and neurocysticercosis (NCC), is primarily due to an inflammatory host reaction to the parasite. Inflammatory cytokines produced by invading T cells, monocytes, and CNS resident cells lead to neuroinflammation which underlie the immunopathology of these infections. Immune molecules, especially cytokines, can therefore emerge as potential biomarker(s) of CNS parasitic infections. In this study, cerebral spinal fluid (CSF) samples from suspected patients with parasitic infections were screened for pathogenic free-living amoebae by culture (n=2506) and PCR (n=275). Six proinflammatory cytokines in smear and culture-negative CSF samples from patients with GAE (n = 2), NCC (n = 7), and CT (n = 23) as well as control (n = 7) patients were measured using the Multiplex Suspension assay. None of the CSF samples tested was positive for neurotropic free-living amoebae by culture and only two samples showed Acanthamoeba 18S rRNA by PCR. Of the six cytokines measured, only IL-6 and IL-8 were significantly increased in all three infection groups compared to the control group. In addition, TNFa levels were higher in the GAE and NCC groups and IL-17 in the GAE group compared to controls. The levels of IL-1b and IFNg were very low in all the infection groups and the control group. There was a correlation between CSF cellularity and increased levels of IL-6, IL-8, and TNFa in 11 patients. Thus, quantifying inflammatory cytokine levels in CSF might help with understanding the level of neuroinflammation in patients with neurotropic parasitic diseases. Further studies with clinico-microbiological correlation in the form of reduction of cytokine levels with treatment and the correlation with neurological deficits are needed.

The superior efficacy of chloroquine over buparvaquone in reducing the chronic cerebral Toxoplasma gondii cysts load and improving the ultrastructural pathology in an immunocompromised murine model

@#Toxoplasma gondii, the etiologic agent of toxoplasmosis, infects about 30 – 50% of the world population. The currently available anti-Toxoplasma agents have serious limitations. The present study aimed to investigate the effects of two antimalarials; buparvaquone (BPQ) and chloroquine (CQ), on immunocompromised mice with chronic cerebral toxoplasmosis, using spiramycin as a reference drug. The assessed parameters included the estimation of mortality rates (MR) among mice of the different study groups, in addition to the examination of the ultrastructural changes in the brain tissues by transmission electron microscopy. The results showed that only CQ treatment could decrease the MR significantly with zero deaths, while both spiramycin and BPQ caused an insignificant reduction of MR compared to the infected non-treated group. All the used drugs decreased the number of mature ruptured cysts significantly compared to the infected non-treated group, while only CQ increased the number of atrophic and necrotic cysts significantly. Furthermore, both spiramycin and BPQ improved the microvasculopathy and neurodegeneration accompanying the infection with different degrees of reactive astrocytosis and neuronal damage with the best results regarding the repair of the microvascular damage with less active glial cells, and normal neurons in the CQ-treated group. In conclusion, this study sheds light on CQ and its excellent impact on treating chronic cerebral toxoplasmosis in an immunocompromised mouse model.

Aspectos clinicoepidemiológicos e imagenológicos de pacientes con virus de inmunodeficiencia humana/sida y diagnóstico de neurotoxoplasmosis / Clinical epidemiological and imaging aspects of patients with human immunodeficiency virus/aids and diagnosis of neurotoxoplasmosis i: en

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.

Effect of Toxoplasma gondii Chinese 1 genotype infections on brain iron metabolism in mice / 中国血吸虫病防治杂志

Objective To investigate the effect of Toxoplasma gondii Chinese 1 genotype infections on host brain iron metabolism and brain damages. Methods Twenty C57BL/6 mice, each weighing 15 to 17 g, were randomly divided into the control and infection groups, of 10 mice in each group. Each mouse in the infection group was injected intraperitoneally with 4 000 tachyzoites of the TgCtwh3 isolate with Chinese 1 genotype, while each mouse in the control group was injected with an equal amount of sterile phosphate-buffered saline (PBS). All mice were sacrificed 6 day post-infection and brain tissues were sampled. The iron levels were measured in mouse brain specimens using inductively coupled plasma mass spectrometry (ICP-MS). The differentially expressed genes were determined between the experimental and control groups using RNA chips and Gene Ontology (GO) term enrichment analysis of differentially expressed genes was performed. The mRNA expression of Toxoplasma gondii surface antigen 1 (TgSAG1) gene and some Zrt- and Irt-like protein (ZIP) family member coding genes was detected by quantitative real-time PCR (qPCR) assay. The ultrastructure of the hippocampus dentate gyrus in mouse brain specimens was observed using optical and electronic microscopy. The glutathione peroxidase 4 (GPx4) expression was determined using Western blotting, and malondialdehyde (MDA) level was measured using thiobarbituric acid (TBA) test. In addition, the optical density (OD) of vascular endothelial growth factor (VEGF) protein was measured using immunohistochemistry. Results Optical microscopy showed cell necrosis in the hippocampus dentate gyrus of mouse brain specimens in the infection group, and electronic microscopy cytoplasmic vacuolization, nuclear atrophy and necrosis, disruption of cristae mitochondriales and increased autophagosome levels in the mouse brain hippocampus specimens in the infection group. The iron level was significantly greater in mouse brain specimens in the infection group than in the control group [(32.92 ± 0.90) μg/g vs. (37.72 ± 1.10) μg/g; t = 3.397, P < 0.01]. RNA chips revealed 721 up-regulated genes and 276 down-regulated genes in mouse brain specimens between the infection and control groups, and the differentially expressed genes were significantly enriched in metal ion binding ability (molecular function). Elevated expression of metal element transporter ZIP2 mRNA (t = 8.659, P < 0.05), reduced GPx4 expression [(1.046 ± 0.025) vs. (0.720 ± 0.101); t = 3.129, P < 0.01], increased MDA level [(4.37 ± 0.33) nmol/mgprot vs. (5.93 ± 0.54) nmol/mgprot; t = 2.451, P < 0.05], and up-regulated mean OD of VEGF protein [(0.348 3 ± 0.017 8) vs. (0.490 6 ± 0.010 5); t = 6.641, P < 0.01] were found in mouse brain specimens in the infection group than in the control group. Conclusions Chinese 1 genotype T. gondii infection results in iron accumulation in brain tissues, reduced antioxidant ability and elevated levels of oxidative stress in mice, suggesting that T. gondii infection may cause brain damages through affecting iron metabolism in host brain tissues.

Toxoplasmosis congénita: la importancia de la adherencia a las guías y las implicaciones clínicas en Colombia / Congenital toxoplasmosis: the importance of adherence to guidelines and clinical implications in Colombia

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.

Toxoplasmosis cerebral luego de un trasplante renal / Cerebral toxoplasmosis after a kidney transplant

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.

Quality of life and handgrip strength of HIV patients diagnosed with neurotoxoplasmosis / Qualidade de vida e força manual em pacientes HIV com diagnóstico de neurotoxoplasmose

Abstract HIV / AIDS epidemic continues to be a major public health problem, and when there is poor adherence to treatment, patients become susceptible to other infections such as toxoplasmosis. The aim of this study was to evaluate the handgrip strength and quality of life of HIV infected patients diagnosed with neurotoxoplasmosis. A cross-sectional study was conducted with 40 HIV-infected patients, with and without diagnosis of neuroxoplasmosis.Sociodemographic and clinical profile information was collected, and handgrip strength and quality of life were evaluated. Almost all patients of both groups used antiretroviral therapy. In the handgrip strength evaluation, no statistical difference was observed for the right and left hand between groups with and without neurotoxoplasmosis (p> 0.05). However, the classifica-1 Federal University of Pará. Gradution of inadequate handgrip strength in the neurotoxoplasmosis group was significantly higher.ate Program in Tropical Diseases. In the quality of life domain, it was observed that financial concern had lower scores in the Belém, PA. Brazil. group with neurotoxoplasmosis (p = 0.0379). It was observed that neurotoxoplasmosis showedno association with epidemiological, clinical, handgrip strength and quality of life variables.2 State University of Pará. Center However, patients with neurotoxoplasmosis showed a trend towards lower muscle strength.

Resumo Atualmente a epidemia do HIV/Aids continua sendo um problema de saúde pública de ampla relevância, e quando não há uma boa aderência do paciente ao tratamento o mesmo torna-se suscetível a outras infecções como a toxoplasmose. Objetivou-se avaliar a força de preensão manual e a qualidade de vida em pacientes infectados pelo HIV com diagnóstico de neurotoxoplasmose. Foi realizado um estudotransversal com 40 pacientes infectados pelo HIV, com e sem diagnóstico de neuroxoplasmose. Foram coletadas informações sociodemográficas, perfil clínico e foram avaliadas a força de preensão manual e a qualidade de vida. Quase todos os pacientes de ambos os grupos utilizavam a terapia antirretroviral.Na avaliação de força de preensão manual não notou-se diferença estatística para a força manual direita e esquerda entre os grupos com e sem neurotoxoplasmose (p>0.05). Contudo, a classificação de inadequado para a força manual no grupo com neurotoxoplasmose foi significativamente maior. Nos domínios da qualidade de vida, observou-se que a preocupação financeira apresentou menores escoresno grupo com neurotoxoplasmose (p=0.0379). Observou-se que a neurotoxoplasmose não demonstrou associação com as variáveis epidemiológicas, clínicas, da força manual e da qualidade de vida. Contudo os pacientes com neurotoxoplasmose apresentaram uma tendência para menor força muscular.

Fotopsias como manifestación inicial de Sida secundario a toxoplasmosis cerebral: reporte de caso / Photopsias as an initial manifestation of AIDS secondary to cerebral toxoplasmosis: case report

RESUMEN La toxoplasmosis cerebral es la infección oportunista más frecuente del sistema nervioso central (SNC) del paciente infectado por el virus de la inmunodeficiencia humana (VIH). Se considera un problema de salud pública por las secuelas físicas y neurosicológicas que genera. Se presenta con una sintomatología muy variable que puede ir desde cefalea, pasar por la fiebre y emesis, hasta las convulsiones y los cambios de comportamiento. No se encontró en la literatura mundial ningún reporte de caso donde se hiciera un diagnóstico de novo de VIH por fotopsias como primera manifestación de toxoplasmosis cerebral. A continuación, se presenta el caso de un paciente masculino, de 39 años, quien consultó por cuadro clínico de dos meses de evolución, constituido por fotopsias en ambos ojos acompañado de cefalea hemicráneana izquierda, sin más síntomas acompañantes. El examen oftalmológico no tuvo hallazgos patológicos, por lo cual se solicitó una tomografía axial computarizada (TAC) simple y contrastado de órbitas y cerebro, por el resultado se realizó una impresión diagnóstica de toxoplasmosis cerebral que fue la presentación inicial de su VIH subyacente.

SUMMARY Cerebral toxoplasmosis is the most frequent opportunistic infection of the central nervous system (CNS) in patients infected with the human immunodeficiency virus (HIV). It is considered a public health problem due to the physical and neurosychological sequels that it generates. It presents with a very variable symptomatology that can be from headache, fever and emesis until convulsions and behavior changes. No case report was found in the world literature where it was new diagnosed of HIV by photopsies as the first manifestation of cerebral toxoplasmosis. The case of a 39-year-old male patient was present. He presented with 2-month clinical course consisting of photopsies in both eyes, accompanied by left hemicranial headache. No more accompanying symptoms. The ophthalmologic examination was without pathological findings, for which simple and contrasted computed axial tomography of orbits and brain was requested where as a result a diagnostic impression of cerebral toxoplasmosis was made wich was the initial presentation of his underlying HIV.

No todo es Zika: toxoplasmosis congénita, ¿aún prevalente en Colombia? / Not everything is Zika: congenital toxoplasmosis, still prevalent in Colombia?

RESUMEN La toxoplasmosis congénita continúa siendo un problema de salud pública. Aun existiendo guías plenamente divulgadas y conocidas, se observa poca implementación de las mismas y falta de adecuada interpretación de pruebas serológicas en gestantes Esto puede generar falta de captación y tratamiento en embarazadas con primoinfección por Toxoplasma gondii. Reportamos una serie de casos, con compromiso neurológico y sistémico (dificultad respiratoria, hepatoesplenomegalia, enterocolitis, calcificaciones cerebrales, trombocitopenia, corioretinis, ascitis, choque). Si bien el virus de Zika causó epidemia en 2015-2016 en Brasil, Colombia y otros países, toxoplasmosis es un diagnóstico diferencial aún prevalente en estos países, con secuelas graves, discapacidad neurológica y riesgo de daño ocular, incluso tardío. Adicionalmente, existen algunas variedades de cepas de T. gondii con comportamiento más agresivo en Latinoamérica, lo cual empeora la presentación de los casos, incluyendo además mayor riesgo de muerte.

ABSTRACT Congenital toxoplasmosis continues to be a public health threat. Even existing guidelines, publicly known, its implementation and lack of appropriate interpretation of serological tests in pregnancy is often observed. This leds to failure in opportunities for positive and known interventions to decrease the fetal risk due to Toxoplasma gondii infection. We reported herein a case series, with variable neurological and systemic compromise (respiratory distress, hepatosplenomegaly, enterocolitis, brain calcifications, thrombocytopenia, ascites, shock), even fatal, calling for awareness about the fact that despite the Zika epidemics in 2015-2016 in Brazil, Colombia and other countries, precisely toxoplasmosis, is a differential diagnosis still prevalent in these territories, that can leds to severe consequences, with neurological disability and risk of ocular damage, even lately. Additionally, with varieties of T. gondii with more aggressive patterns in Latin America, which make worse those cases, including also a higher risk of death.

Hallazgos de imagen en pacientes con Neurotoxoplasmosis y VIH/SIDA en el Hospital Carlos Andrade Marín, durante el período de enero 2010 a julio 2012 / Imaging findings in patients with neurotoxoplasmosis and HIV/AIDS in Carlos Andrade Marin Hospital during the January 2010 to July 2012 period

Introducción: El síndrome de inmunodeficiencia adquirida afecta el sistema inmune de la persona, particularmente a los linfocitos T. La toxoplasmosis cerebral constituye la infección oportunista más común en pacientes con VIH-SIDA, aparece en sujetos con menos de 100 linfocitos T CD4/mm3. Ante la sospecha clínica de neurotoxoplasmosis se deben solicitar estudios de imagen como tomografía de cráneo o resonancia magnética nuclear de encéfalo. El objetivo del presente trabajo es describir en un grupo de pacientes los hallazgos de imagen con neurotoxoplasmosis y VIH/SIDA. Materiales y métodos: Serie de casos de 27 pacientes cuyos exámenes de imagen fueron revisados conjuntamente con el contaje CD4 y las neuroimágenes (RMN), de pacientes con diagnóstico de VIH/SIDA y Toxoplasmosis, de enero 2010 a julio 2012, en el Hospital Carlos Andrade Marín. Resultados: Hubo predominio de varones (8:1) entre los pacientes con un contaje CD4 inferior a 100/mm3. El mayor porcentaje de lesiones en la RMN fueron grado 2, correspondientes a la clasificación de lesiones por imagen de toxoplasmosis cerebral, caracterizadas por ser lesiones ocupantes de espacio, que tienen realce y edema perilesional; con hipointensidad en T1 e hiperintensidad en T2. La mayor parte pertenecieron a la clase C3 de la clasificación CDC y hubo un predominio de grado 2, de la clasificación de neurotoxoplasmosis por imágenes. Discusión: Las imágenes de neurotoxoplasmosis demostradas con RMN en pacientes con VIH/SIDA son de mucha utilidad para el diagnóstico y seguimiento de esta entidad.

Abstract Introduction: Acquired immunodeficiency syndrome impairs the immune system, particularly T lymphocytes. Cerebral toxoplasmosis is the leading cause of opportunistic infection of the central nervous system (CNS) in HIV/AIDS patients, when they have CD4+ counts fewer than 100 cells/mm3. Facing a patient with clinical suspicion of neurotoxoplasmosis, a CT scan or MRI should be asked. The aim of this paper was describing image findings of a group of HIV patients with neurotoxoplasmosis Methods: Case serie involving 27 patients whose medical records were analyzed. It includes the results of clinical exams, CD4 counts and MRI files with both diagnosis HIV/AIDS and toxoplasmosis, from January 2010 to July 2012, at Carlos Andrade Marin Hospital. Results: The study sample included more men than women (8:1). Most patients had a CD4 count fewer than 100 cells/mm3. Grade 2 lesions were frequent in the MRI, corresponding to h space-occupying lesions with enhancement and perilesional edema; showing hypointensity on T1 and hyperintensity on T2. Most of the patients were stratified as C3 class from CDC classification. Discusion: HIV/AIDS patients with a significant lower CD4 count should have a CT scan or MRI asked, in order to identify neurotoxoplasmosis.

Múltiples infecciones oportunistas concurrentes al sistema nervioso central en paciente VIH positivo y su respuesta al TARGA: reporte de un caso / Multiple concurrent central nervous system opportunistic infections in an HIV-positive patient and his response to HAART: a case report

En el contexto de una severa inmunodepresión existe una marcada dificultad para hacer diagnóstico definitivo de las infecciones oportunistas que son causa principal de morbilidad y mortalidad. La presencia de infecciones del SNC durante la evolución del paciente con VIH, es frecuente, siendo menos habitual la presencia múltiple y concurrente de éstas, pues tal situación somete a los pacientes a peor pronóstico. Por este motivo se muestra el estudio de un paciente que presentó múltiples infecciones oportunistas en el SNC, quien tras iniciar y continuar el TARGA mostró buena evolución. Caso clínico: varón de 51 años con antecedentes de alcoholismo que acude al hospital con s¡ndrome de hipertensión endocraneana. Es diagnosticado de meningitis criptocócica e infección por VIH estadio C sin TARGA. Durante el tratamiento se evidenci ademas infecciones oportunistas concurrentes, como meningitis tuberculosa, leucoencefalopatia multifocal progresiva y toxoplasmosis cerebral; conjuntamente presentó síndrome inflamatorio de reconstitución inmunológica (IRIS). El paciente al iniciar y mantener el TARGA se recuperó ¡ntegramente y manifestó buena evolución, actualmente es tratado ambulatoriamente y no se ha complicado. Interpretación: los episodios múltiples y concurrentes de infecciones oportunistas del SNC descritos as¡ como el IRIS, generalmente inducen a los pacientes a mal pronóstico, sin embargo, son pocos los casos que se recuperan copiosamente y muestran buen pronóstico. Este es un caso particular de recuperación después de seguir el TARGA correctamente. Se describe este reporte por su importancia para valorar una apropiada adherencia al TARGA.

In the context of severe immunosuppression, there is a marked difficulty in making a definitive diagnosis of opportunistic infections, which are leading causes of morbidity and mortality. The presence of CNS infections during the evolution of HIV patients is common, less common being multiple and concurrent presence of these. This situation undergoes patients with poor prognosis. For this reason we report the case of a patient who developed multiple opportunistic infections in the CNS, who after HAART initiation and continuation showed good performance. Clinical case: 51 year old male with a history of alcoholism, was admitted to hospital with intracranial hypertension syndrome. He was diagnosed with cryptococcal meningitis and HIV infection stage C without HAART. During treatment also showed concurrent opportunistic infections such as TB meningitis, progressive multifocal leukoencephalopathy and cerebral toxoplasmosis, jointly presented immune reconstitution inflammatory syndrome (IRIS). The patient, initiating and maintaining HAART, fully recovered and showed good performance. Currently he is treated as an outpatient and has no complications. Interpretation: The multiple concurrent episodes of opportunistic infections of the CNS described, as well as the IRIS, generally induce poor prognosis in patients. However, there are few cases that improve and show good prognosis. This is a particular case of recovery after HAART follow correctly. We describe this report because of its importance in assessing adherence to HAART.

Features to validate cerebral toxoplasmosis

Introduction Neurotoxoplasmosis (NT) sometimes manifests unusual characteristics. Methods We analyzed 85 patients with NT and AIDS according to clinical, cerebrospinal fluid, cranial magnetic resonance, and polymerase chain reaction (PCR) characteristics. Results In 8.5%, focal neurological deficits were absent and 16.4% had single cerebral lesions. Increased sensitivity of PCR for Toxoplasma gondii DNA in the central nervous system was associated with pleocytosis and presence of >4 encephalic lesions. Conclusions Patients with NT may present without focal neurological deficit and NT may occur with presence of a single cerebral lesion. Greater numbers of lesions and greater cellularity in cerebrospinal fluid improve the sensitivity of PCR to T gondii. .

Cerebral Toxoplasmosis Combined with Disseminated Tuberculosis

A 24-year-old man presented with mental change, fever, abdominal pain, tenderness and palpable mass on the lower abdomen. He was a non-Korean engineer and did not accompany a legal guardian, so medical history taking was difficult due to his mental status. Brain magnetic resonance imaging showed multiple rim-enhanced lesions of the brain, and abdominal computed tomography showed huge paraspinal abscess. Chest X-ray and computed tomography showed poorly defined nodular opacities. We initially thought that this patient was infected with toxoplasmosis with typical cerebral image finding and immunoglobulin laboratory finding of cerebrospinal fluid and serum study. The abdominal abscess was confirmed as tuberculosis through the pathologic finding of caseous necrosis. We used anti-tuberculosis medication and anti-toxoplasmosis medication for almost 4 months, and then his clinical state and radiological findings were considerably improved.

Importance of high IgG anti-Toxoplasma gondii titers and PCR detection of T. gondii DNA in peripheral blood samples for the diagnosis of AIDS-related cerebral toxoplasmosis: a case-control study

BACKGROUND: Cerebral toxoplasmosis (CT) continues to cause significant morbidity and mortality in human immunodeficiency virus (HIV)-infected patients in Brazil. In clinical practice, the initial diagnosis is usually presumptive and alternative diagnosis tools are necessary. Our objective was to evaluate whether the detection of high titers of IgG anti-Toxoplasma gondii and T. gondii DNA in blood samples are associated with the diagnosis of CT. METHODS: In this case-control study we included 192 patients with HIV-1 infection: 64 patients with presumptive CT (cases) and 128 patients with other diseases (controls). Blood samples to perform indirect immunofluorescense reaction (IFI) to detect anti-T. gondii IgG antibodies and polymerase chain reaction (PCR) were collected before or within the first three days of anti-Toxoplasma therapy. Two multivariate logistic regression models were performed: one including the variable qualitative serology and another including quantitative serology. RESULTS: In the first model, positive IgG anti-T. gondii (OR 4.7, 95 percent CI 1.2-18.3; p = 0.027) and a positive T. gondii PCR result (OR 132, 95 percent CI 35-505; p < 0.001) were associated with the diagnosis. In the second model, IgG anti-T. gondii titres > 1:1024 (OR 7.6, 95 percent CI 2.3-25.1; p = 0.001) and a positive T. gondii PCR result (OR 147, 95 percent CI 35-613; p < 0.001) were associated with the diagnosis. CONCLUSIONS: Quantitative serology and molecular diagnosis in peripheral blood samples were independently associated with the diagnosis of CT in HIV-infected patients. These diagnostic tools can contribute to a timely diagnosis of CT in settings where Toxoplasma infection is common in the general population.

Molecular diagnosis of cerebral toxoplasmosis: comparing markers that determine Toxoplasma gondii by PCR in peripheral blood from HIV-infected patients

As cerebral toxoplasmosis is the most common cerebral focal lesion in AIDS patients, this study evaluated three PCR markers for diagnosis, since some limitations remain present, such as low parasite levels in some clinical samples. The molecular markers were B22-B23 and Tg1-Tg2 (based on the B1 gene) and Tox4-Tox5 (non-coding fragment, repeated 200-300-fold). DNA samples from 102 AIDS patients with previously known diagnosis were analyzed. The cerebral toxoplasmosis group was constituted of DNA extracted from the blood of 66 AIDS patients, which was collected before or until the third day of the therapy for toxoplasmosis. DNA from the blood of 36 AIDS patients with other neurologic opportunistic infections was used as control group. Sensitivities of B22-B23, Tg1-Tg2, and Tox4-Tox5 markers were of 95.5 percent, 93.9 percent, and 89.3 percent, respectively. In the control group, the specificities were of 97.2 percent (B22-B23), 88.9 percent (Tg1-Tg2), and 91.7 percent (Tox4-Tox5). The association of at least two markers increased the PCR sensitivity and specificity. The concordance index between two markers varied from 83.3 percent to 93.1 percent. These data demonstrated that all markers evaluated here were highly sensitive for T. gondii determination, although B22-B23 has been shown to be the best. The association of two markers increases PCR sensitivity, but the procedure was more expensive and time-consuming.

Hallazgos neuropatológicos de la infección por VIH-SIDA: estudio de autopsias en el Hospital Universitario de Santander, Bucaramanga, Colombia / Neuropathologic features of the infection HIV-AIDS: study autopsy in the Hospital Universitario de Santander, Bucaramanga, Colombia

Objetivo: Describir las alteraciones macro y microscópicas observadas en el sistema nervioso central (SNC) de pacientes que fallecieron por la infección con VIH-SIDA. Metodología: Estudio retrospectivo de autopsias del 1 de enero de 2004 al 31 de diciembre de 2007 en un hospital público de tercer nivel en la ciudad de Bucaramanga, Santander. Resultados: El hallazgo neuropatológico más común en pacientes que fallecieron por la infección VIH-SIDA fue toxoplasmosis cerebral, 17 casos (28.3%) luego criptococosis cerebral, 7 casos (11.6%), tuberculosis del SNC, 3 casos (5%), encefalopatía por HIV, 2 casos (3.3%), meningitis piógena, un caso (1.6%) y hallazgos inespecíficos,2 casos (3.3%).  No hubo lesiones neoplásicas, infecciones por citomegalovirus, herpes, histoplasmosis ni leucoencefalopatía multifocal progresiva (LMP) en ninguno de los casos. En el presente estudio se encontraron cambios en el SNC en 32 casos (53.1%), que, después del respiratorio (39-65%), fue el sistema más afectado por las complicaciones relacionadas con la enfermedad por VIH. La presencia de lesión directa (encefalitis por HIV) y al mismo tiempo infección oportunista se encontró sólo en un caso (1.6%). Conclusiones: En Bucaramanga las infecciones oportunistas fueron las complicaciones más frecuentes y graves a nivel del SNC en los enfermos con VIH-SIDA, de ellas la toxoplasmosis cerebral fue la que más comprometió el SNC de los pacientes con infección con VIH-SIDA, y se expresó morfológicamente como una meningoencefalitis necrosante, ubicada de manera preferencial en la región de los ganglios basales.

Objective: To describe the macroscopic and microscopic alterations observed in the central nervous system (CNS) in patients who died through HIV-AIDS infection. Method used: Retrospective study of autopsies from January 1st 2004 to December 31st 2007 in a third-level public hospital at Bucaramanga, Santander.Results: The most common neuro-pathological findings in patients who died through HIV-AIDS infection were cerebral toxoplasmosis, 17 cases (28.3%); followed by cerebral cryptococcosis, 7 cases (11.6%); CNS tuberculosis, 3 cases (5%); HIV encephalitis, 2 cases (3.3%); and bacterial meningitis, 1 case (1.6%). Neoplasm lesions, CMV infection, herpes infection, histoplasmosis, and progressive multifocal leucoencephalopathy (PML) were not found in any case. In this study, changes were seen in the CNS in 32 cases (53.1%), which after the respiratory system (39-65%) was the most affected system for complications related to HIV infection. HIV-induced encephalopathy simultaneously with an opportunistic infection was only found in 1 case (1.6 %). Conclusion: In Bucaramanga, opportunistic infections are the most frequent and serious complications in the CNS of individuals with HIV-AIDS; among them cerebral toxoplasmosis was the most frequently observed complication in the CNS of patients with HIV-AIDS, appearing morphologically as a meningoencephalitis with necrosis and large lesions localized in the gangliobasal region.

Neurotoxoplasmosis diagnosis for HIV-1 patients by real-time PCR of cerebrospinal fluid

Encephalitis caused by Toxoplasma gondii is the most common cause of central nervous system damage in patients with acquired immunodeficiency syndrome (AIDS). Toxoplasma may infect any of the brain cells, thus leading to non-specific neurotoxoplasmosis clinical manifestations including focused or non-focused signs and symptoms of central nervous system malfunction. Clinical development ranges from insidious display during weeks to experiencing acute general confusion or ultimately fatal onset. Cerebral toxoplasmosis occurs in advanced stages of immunodeficiency, and the absence of anti-toxoplasmosis antibodies by the immunofluorescence method does not allow us to rule out its diagnosis. As specific therapy begins, diagnosis confirmation is sought through clinical and radiological response. There are few accurate diagnosis methods to confirm such cases. We present a method for T. gondii DNA detection by real time PCR-Multiplex. Fifty-one patients were evaluated; 16 patients had AIDS and a presumptive diagnosis for toxoplasmosis, 23 patients were HIV-positive with further morbidities except neurotoxoplasmosis, and 12 subjects were HIV-negative control patients. Real time PCR-Multiplex was applied to these patients' cephalorachidian liquid with a specific T. gondii genome sequence from the 529bp fragment. This test is usually carried out within four hours. Test sensitivity, specificity, positive predictive value, and negative predictive value were calculated according to applicable tables. Toxoplasma gondii assay by real time Multiplex of cephalorachidian fluid was positive for 11 out of 16 patients with AIDS and a presumptive diagnosis for cerebral toxoplasmosis, while none of the 35 control patients displayed such a result. Therefore, this method allowed us to achieve 68.8 percent sensitivity, 100 percent specificity, 100 percent positive predictive value, and 87.8 percent negative predictive value. Real time PCR on CSF allowed high specificity...

Ventriculitis: a rare case of primary cerebral toxoplasmosis in AIDS patient and literature review

Cerebral toxoplasmosis remains the most important neurological opportunistic infection and the most common cause of intracerebral mass lesion in patients with acquired immunodeficiency syndrome (AIDS). We report a case of an adult AIDS patient with an atypical pattern of toxoplasma encephalitis, presenting with ventriculitis and obstructive hydrocephalus without any focal parenchymal lesion.