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

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.

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.

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]: : 35­50) anos, e 50% (n = 22) dos pacientes eram do sexo masculino. A contagem mediana de linfócitos T CD4+ foi de 50 (IIQ:15­94) 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.

Blastic plasmacytoid dendritic cell neoplasm and cerebral toxoplasmosis: a case report.

BACKGROUND: The present case contributes to the limited literature on central nervous system involvement of blastic plasmacytoid dendritic cell neoplasm (BPDCN).  CASE PRESENTATION : A 63-year-old male presented to the department of neurology with a three-day history of rapidly progressing headache, fatigue, and confusion. Physical examination revealed multiple bruise-like skin lesions. Initial laboratory workup raised suspicion of acute leukemia, and a brain computer tomography identified several hyperdense processes. A bone marrow biopsy gave the diagnosis BPDCN, a rare and aggressive hematologic malignancy derived from plasmacytoid dendritic cells with a poor prognosis. Lumbar puncture showed not only signs of BPDCN, but also cerebral toxoplasmosis, thus providing a differential diagnosis. Despite intensive systemic and intrathecal chemotherapy, the patient died 25 days later due to multi-organ failure. DISCUSSION: The exact incidence of BPDCN is unknown and perhaps underestimated but may account for 0.5 - 1% of all hematological malignancies. The median age at onset is 60 to 70 years, and most patients are men. Cutaneous lesions are the most frequent clinical manifestation at diagnosis. Other symptoms present at time of diagnosis or during disease progression include lymphadenopathy, splenomegaly and cytopenia caused by bone marrow involvement. Although the majority of BPDCN patients have no symptoms or signs of central nervous system involvement, plasmacytoid dendritic cells have been detected in the cerebrospinal fluid in more than 50%. CONCLUSIONS: This case highlights the importance of considering hematological malignancies as a differential diagnosis in patients developing acute neurological symptoms and raises suspicion of a possible association between toxoplasmosis and hematological malignancies.

Social preference is maintained in mice with impaired startle reflex and glutamate/D-serine imbalance induced by chronic cerebral toxoplasmosis.

Toxoplasma gondii is an opportunistic protozoan pathogen with a wide geographic distribution. The chronic phase of toxoplasmosis is often asymptomatic in humans and is characterized by tissue cysts throughout the central nervous system and muscle cells. T. gondii and other pathogens with tropism for the central nervous system are considered risk factors in the etiology of several neuropsychiatric disorders, such as schizophrenia and bipolar disorder, besides neurological diseases. Currently, it is known that cerebral toxoplasmosis increases dopamine levels in the brain and it is related to behavioral changes in animals and humans. Here we evaluate whether chronic T. gondii infection, using the cystogenic ME-49 strain, could induce behavioral alterations associated with neuropsychiatric disorders and glutamatergic neurotransmission dysfunction. We observed that the startle amplitude is reduced in the infected animals as well as glutamate and D-serine levels in prefrontal cortical and hippocampal tissue homogenates. Moreover, we did not detect alterations in social preference and spontaneous alternation despite severe motor impairment. Thus, we conclude that behavioral and cognitive aspects are maintained even though severe neural damage is observed by chronic infection of C57Bl/6 mice with the ME-49 strain.

[Difficulties of cerebral toxoplasmosis diagnosis in a patient with multiple sclerosis and HIV]. / Trudnosti diagnostiki tserebral'nogo toksoplazmoza u patsientki s rasseyannym sklerozom i VICh-infektsiei.

Toxoplasmosis is a widespread parasitic disease. It is caused by an intracellular parasite Toxoplasma gondii. It can affect various tissues and organs, forming cysts and continuing to replicate within them. In people with intact immune system, tissue cysts remain in latent state throughout their whole life. However, in cases of cellular immunodeficiency the infection can be reactivated, which leads to secondary generalization of the process. People with HIV most commonly present with cerebral toxoplasmosis. Non-specific neuroimaging signs, as well as absence of pathognomonic symptoms and specific laboratory data lead to difficulties of cerebral toxoplasmosis diagnosis, particularly in the cases with a history of multiple sclerosis that has similar clinical symptoms and brain MRI data suggesting of tumefactive multiple sclerosis image. A clinical case of cerebral toxoplasmosis in a female patient with multiple sclerosis and HIV infection is described.

Diffuse encephalitic toxoplasmosis in HIV.

This case demonstrates an atypical radiological presentation of cerebral toxoplasmosis in a 62-year-old HIV-positive patient. The diagnosis is discussed alongside MRI imaging, laboratory results and treatment. Central nervous system toxoplasmosis is typically associated with ring enhancing lesions on neuroimaging with contrast, but the radiology for this patient shows diffuse white matter changes and ependymal enhancement, which would normally suggest an alternative diagnosis.

Toxoplasmosis and Neuropsychological Effects

Toxoplasma gondii is an intracellular protozoan parasite. Approximately 30% of the global population is infected by T. gondii. In chronically infected individuals, the parasite resides in tissue cysts, especially in the brain. There is a growing interest in the role of parasitologic agents in the causation of neuropsychological disorders. In this review, we have explained the interactions between Toxoplasma and its host, mechanisms, and consequences on neural and psychological diseases.

Toxoplasmosis of the central nervous system: Manifestations vary with immune responses.

Toxoplasmosis is an opportunistic infection caused by Toxoplasma gondii (TG), which affects one third of the global human population and commonly involves the central nervous system (CNS)/brain despite the so-called CNS immune privilege. Symptomatic clinical disease of TG infection is much more commonly associated with immunodeficiency; clinicopathological manifestations of CNS toxoplasmosis are linked to individual immune responses including the CNS infiltration of T-cells that are thought to prevent the disease. In patients with autoimmune diseases, immune status is complicated mainly byimmunosuppressant and/or immunomodulatory treatment but typically accompanied by infiltration of T-cells that supposedly fight against toxoplasmosis. In this article, we review characteristics of CNS toxoplasmosis comparatively in immunocompromised patients, immunocompetent patients, and patients with coexisting autoimmune diseases, as well as CNS immune responses to toxoplasmosis with a representative case to demonstrate brain lesions at different stages. In addition to general understanding of CNS toxoplasmosis, our review reveals that clinical manifestations of CNS toxoplasmosis are commonly nonspecific, and incidental pathological findings of TG infection are relatively common in immunocompetent patients and patients with autoimmune diseases (compared to immunocompromised patients); CNS immune responses such as T-cell infiltrates vary in acute and chronic lesions of brain toxoplasmosis.

Cerebral toxoplasmosis in HIV-infected patients over 2015-2018 (a case study of Russia).

Cerebral toxoplasmosis is a leading cause of the central nervous system disorders in acquired immune deficiency syndrome. This study aimed to investigate the clinical course of cerebral toxoplasmosis in human immunodeficiency virus (HIV)-infected individuals. The study included 90 HIV-infected patients with cerebral toxoplasmosis, who underwent inpatient treatment. In case of positive enzyme immunoassay, HIV infection was confirmed with the immunoblot test. The HIV-1 ribonucleic acid level was determined using the polymerase chain reaction method. The flow cytometry was used for counting CD4 (cluster of differentiation 4 cells). Pathomorphological examination included the autopsy, gross and microscopic examination of internal organs, histological and other methods. The incidence of cerebral toxoplasmosis significantly increases at the CD4 count below 100 cells/µl, P < 0.001, and at the HIV viral load above 50 copies/ml, P < 0.05. The clinical picture of cerebral toxoplasmosis included focal symptoms, cognitive impairment, toxic syndrome, mild cerebral symptoms and a meningeal symptom. Given the absence of a specific clinical picture and the absence of abnormal laboratory and instrumental findings, the cerebral toxoplasmosis needs to be diagnosed with a number diagnostic methods combined: clinical examination, laboratory testing, immunological examination, molecular genetic testing and neuroradiological imaging.

A study for precision diagnosing and treatment strategies in difficult-to-treat AIDS cases and HIV-infected patients with highly fatal or highly disabling opportunistic infections.

BACKGROUND: An increased frequency of toxoplasma encephalitis, caused by Toxoplasma gondii, has been reported in AIDS patients, especially in those with CD4+ T cell counts <100 cells/µL. Several guidelines recommend the combination of pyrimethamine, sulfadiazine, and leucovorin as the preferred regimen for AIDS-associated toxoplasma encephalitis. However, it is not commonly used in China due to limited access to pyrimethamine and sulfadiazine. The synergistic sulfonamides tablet formulation is a combination of trimethoprim (TMP), sulfadiazine and sulfamethoxazole (SMX), and is readily available in China. Considering its constituent components, we hypothesize that this drug may be used as a substitute for sulfadiazine and TMP-SMX. We have therefore designed the present trial, and propose to investigate the efficacy and safety of synergistic sulfonamides combined with clindamycin for the treatment of toxoplasma encephalitis. METHODS/DESIGN: This study will be an open-labeled, multi-center, prospective, randomized, and controlled trial. A total of 200 patients will be randomized into TMP-SMX plus azithromycin group, and synergistic sulfonamides plus clindamycin group at a ratio of 1:1. All participants will be invited to participate in a 48-week follow-up schedule once enrolled. The primary outcomes will be clinical response rate and all-cause mortality at 12 weeks. The secondary outcomes will be clinical response rate and all-cause mortality at 48 weeks, and adverse events at each visit during the follow-up period. DISCUSSION: We hope that the results of this study will be able to provide reliable evidence for the efficacy and safety of synergistic sulfonamides for its use in AIDS patients with toxoplasma encephalitis. TRIAL REGISTRATION: This study was registered as one of 12 clinical trials under the name of a general project at chictr.gov on February 1, 2019, and the registration number of the general project is ChiCTR1900021195. This study is still recruiting now, and the first patient was screened on March 22, 2019.

Plasma extracellular microRNAs are related to AIDS/cerebral toxoplasmosis co-infection.

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.

Concomitant Central Nervous System Toxoplasmosis and Seronegative Disseminated Coccidioidomycosis in a Newly Diagnosed Acquired Immune Deficiency Syndrome Patient.

Opportunistic infections (OIs) are a significant cause of morbidity and mortality in immunosuppressed patients and may be due to bacteria, virus, protozoa, or fungi. Toxoplasmosis is a common cause of central nervous system infection in human immunodeficiency virus (HIV) patients. Coccidioidomycosis is a relatively common fungal infection that may lead to disseminated disease and fungemia in immune-compromised hosts living in endemic regions. This single-patient case report documents the presentation, diagnosis, management, and outcome of concomitant central nervous system toxoplasmosis and diffuse miliary pneumonia with fungemia due to disseminated seronegative Coccidioides immitis in a 33-year-old male patient recently diagnosed with chronic advanced HIV. Impaired cellular immune function, such as defects in the IL-12/IFN-γ pathway or T-helper IL-17-mediated response, is associated with increased severity of coccidioidomycosis. Fungemia and acute respiratory distress syndrome are both associated with very high mortality in coccidioidomycosis. In HIV hosts, negative Coccidioides serology can be seen in up to 25% of cases and therefore other diagnostic modalities should be initiated promptly and simultaneously. This case demonstrates simultaneous OI in the setting of advanced acquired immune deficiency syndrome and emphasizes the need for early diagnosis of HIV and OI in order to ensure prompt initiation of antiretroviral therapy, prophylactic, and therapeutic medications.