Balamuthia mandrillaris Granulomatous Amoebic Encephalitis: The First African Experience.

We report the first case of Balamuthia mandrillaris granulomatous amoebic encephalitis definitively acquired in Africa. Our case emphasizes initial nonspecific dermatological features, delays in confirmation of the diagnosis, difficulties accessing recommended medication, and uncertainty about optimal treatment of a disease with a frequently fatal outcome.

Case Report: Ascending Myelo-Encephalitis after a Penetrating Injury to the Foot: An Atypical Case of Neuromelioidosis.

Organisms penetrate the central nervous system (CNS) via three routes. The commonest is the hematogenous route, and other routes include contiguous or penetrating injury or rarely via retrograde axoplasmic route. Although the axoplasmic highway is often used by viruses, only a few bacteria are known to penetrate the CNS via this route. We present a 57-year-old man who developed a penetrating injury while working in a field. Over the next 4 months, he developed pain at the site of the poorly healing wound, which ascended up the right leg and presented as a conus-cauda syndrome. Magnetic resonance imaging (MRI) showed an enhancing intradural intramedullary enhancing lesion in the conus on the right side with cord edema from D11 to L1 level. Extensive evaluation was negative, and he continued to progress to holocord myelitis and developed bilateral corticospinal tract lesions ("tractopathy") in the brain stem and internal capsule. He died after developing a right-sided cerebritis with mass effect. Tissue biopsy from the brain at the time of decompressive craniectomy grew Burkholderia pseudomallei and confirmed a diagnosis of neuromelioidosis (NM). We reviewed the literature for NM, its variable presentations, and the concept of an "infectious tractopathy" and imaging findings which could generate suspicion of this entity.

Nanoparticles based therapeutic efficacy against Acanthamoeba: Updates and future prospect.

Acanthamoeba sp. is a free living amoeba that causes severe, painful and fatal infections, viz. Acanthamoeba keratitis and granulomatous amoebic encephalitis among humans. Antimicrobial chemotherapy used against Acanthamoeba is toxic to human cells and show side effects as well. Infections due to Acanthamoeba also pose challenges towards currently used antimicrobial treatment including resistance and transformation of trophozoites to resistant cyst forms that can lead to recurrence of infection. Therapeutic agents targeting central nervous system infections caused by Acanthamoeba should be able to cross blood-brain barrier. Nanoparticles based drug delivery put forth an effective therapeutic method to overcome the limitations of currently used antimicrobial chemotherapy. In recent years, various researchers investigated the effectiveness of nanoparticles conjugated drug and/or naturally occurring plant compounds against both trophozoites and cyst form of Acanthamoeba. In the current review, a reasonable effort has been made to provide a comprehensive overview of various nanoparticles tested for their efficacy against Acanthamoeba. This review summarizes the noteworthy details of research performed to elucidate the effect of nanoparticles conjugated drugs against Acanthamoeba.

A Surviving Case of Acanthamoeba Granulomatous Amebic Encephalitis in a Hematopoietic Stem Cell Transplant Recipient.

BACKGROUND Acanthamoeba are free-living amoebae with potential to infect immunocompromised hosts. The mortality rate of granulomatous amebic encephalitis (GAE) due to Acanthamoeba exceeds 90% and there are currently no reports of survival of this infection in recipients of hematopoietic stem cell transplant. CASE REPORT We report herein the case of a 32-year-old man presenting to our service with abrupt neurological deterioration and seizures 5 months after allogeneic stem cell transplantation for Hodgkin lymphoma. Clinical and imaging findings were non-specific at presentation. Multiple circumscribed, heterogenous, mass-like lesions were identified on MRI. Brain biopsy was performed and revealed multiple cysts and trophozoites suggesting a diagnosis of granulomatous amebic encephalitis. PCR testing confirmed Acanthamoeba. Treatment with miltefosine, metronidazole, azithromycin, fluconazole, pentamidine isethionate, and co-trimoxazole was instituted and the patient survived and shows continued improvement with intensive rehabilitation. CONCLUSIONS We report the first successful outcome in this setting. The diagnosis would have been missed on cerebrospinal fluid analysis alone, but was rapidly made by histological analysis of brain biopsy. This diagnostically challenging infection is likely under-recognized. Early brain biopsy and commencement of a prolonged miltefosine-containing anti-ameba regimen can be curative.

Metformin-coated silver nanoparticles exhibit anti-acanthamoebic activities against both trophozoite and cyst stages.

Acanthamoeba castellanii is an opportunistic protozoan responsible for serious human infections including Acanthamoeba keratitis and granulomatous amoebic encephalitis. Despite advances in antimicrobial therapy and supportive care, infections due to Acanthamoeba are a major public concern. Current methods of treatment are not fully effective against both the trophozoite and cyst forms of A. castellanii and are often associated with severe adverse effects, host cell cytotoxicity and recurrence of infection. Therefore, there is an urgent need to develop new therapeutic approaches for the treatment and management of Acanthamoebic infections. Repurposing of clinically approved drugs is a viable avenue for exploration and is particularly useful for neglected and rare diseases where there is limited interest by pharmaceutical companies. Nanotechnology-based drug delivery systems offer promising approaches in the biomedical field, particularly in diagnosis and drug delivery. Herein, we conjugated an antihyperglycemic drug, metformin with silver nanoparticles and assessed its anti-acanthamoebic properties. Characterization by ultraviolet-visible spectrophotometry and atomic force microscopy showed successful formation of metformin-coated silver nanoparticles. Amoebicidal and amoebistatic assays revealed that metformin-coated silver nanoparticles reduced the viability and inhibited the growth of A. castellanii significantly more than metformin and silver nanoparticles alone at both 5 and 10 µM after 24 h incubation. Metformin-coated silver nanoparticles also blocked encystation and inhibited the excystation in Acanthamoeba after 72 h incubation. Overall, the conjugation of metformin with silver nanoparticles was found to enhance its antiamoebic effects against A. castellanii. Furthermore, the pretreatment of A. castellanii with metformin and metformin-coated silver nanoparticles for 2 h also reduced the amoebae-mediated host cell cytotoxicity after 24 h incubation from 73% to 10% at 10 µM, indicating that the drug-conjugated silver nanoparticles confer protection to human cells. These findings suggest that metformin-coated silver nanoparticles hold promise in the improved treatment and management of Acanthamoeba infections.

Targeted Theranostic of Cryptococcal Encephalitis by a Novel Polypyridyl Ruthenium Complex.

Cryptococcus neoformans (C. neoformans) is one of the most well-known zoonotic fungal pathogens. Cryptococcal encephalitis remains a major cause of morbidity and mortality in immunocompromised hosts. Effective and targeting killing of C. neoformans in the brain is an essential approach to prevent and treat cryptococcal encephalitis. In this study, a fluorescent polypyridyl ruthenium complex RC-7, {[phen2Ru(bpy-dinonyl)](PF6)2 (phen = 1,10-phenanthroline, bpy-dinonyl = 4,4'-dinonyl-2,2'-bipyridine)}, was screened out, which showed a highly fungicidal effect on C. neoformans. The values of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) in antifungal activities were significantly lower than fluconazole as the control. Moreover, RC-7 was prepared as a brain-targeting nanoliposome (RDP-liposome; RDP is a peptide derived from rabies virus glycoprotein) for in vivo application. The results revealed that the liposomes could accumulate in the encephalitis brain and play an antifungal role. Compared with the cryptococcal encephalitis model mice, the RDP-liposomes remarkably prolonged the survival days of the encephalitis-bearing mice from 10 days to 24 days. Here, we introduce a polypyridyl ruthenium complex that could be used as a novel antifungal agent, and this study may have a broad impact on the development of targeted delivery based on ruthenium complex-loaded liposomes for theranostics of cryptococcal encephalitis.

Diagnosis of Chagasic Encephalitis by Sequencing of 28S rRNA Gene.

We report a case of chagasic encephalitis diagnosed by 28S rRNA sequencing. The diagnosis of chagasic encephalitis is challenging, given the broad differential diagnosis for central nervous system lesions in immunocompromised patients and low sensitivity of traditional diagnostics. Sequencing should be part of the diagnostic armamentarium for potential chagasic encephalitis.

Innovative Methodology in the Discovery of Novel Drug Targets in the Free-Living Amoebae.

Despite advances in drug discovery and modifications in the chemotherapeutic regimens, human infections caused by free-living amoebae (FLA) have high mortality rates (~95%). The FLA that cause fatal human cerebral infections include Naegleria fowleri, Balamuthia mandrillaris and Acanthamoeba spp. Novel drug-target discovery remains the only viable option to tackle these central nervous system (CNS) infection in order to lower the mortality rates caused by the FLA. Of these FLA, N. fowleri causes primary amoebic meningoencephalitis (PAM), while the A. castellanii and B. Mandrillaris are known to cause granulomatous amoebic encephalitis (GAE). The infections caused by the FLA have been treated with drugs like Rifampin, Fluconazole, Amphotericin-B and Miltefosine. Miltefosine is an anti-leishmanial agent and an experimental anti-cancer drug. With only rare incidences of success, these drugs have remained unsuccessful to lower the mortality rates of the cerebral infection caused by FLA. Recently, with the help of bioinformatic computational tools and the discovered genomic data of the FLA, discovery of newer drug targets has become possible. These cellular targets are proteins that are either unique to the FLA or shared between the humans and these unicellular eukaryotes. The latter group of proteins has shown to be targets of some FDA approved drugs prescribed in non-infectious diseases. This review out-lines the bioinformatics methodologies that can be used in the discovery of such novel drug-targets, their chronicle by in-vitro assays done in the past and the translational value of such target discoveries in human diseases caused by FLA.

Granulomatous amebic encephalitis caused by Acanthamoeba in an immuncompetent child.

Sütçü M, Aktürk H, Gülümser-Sisko S, Acar M, Erol OB, Somer A, Bilgiç B, Salman N. Granulomatous amebic encephalitis caused by Acanthamoeba in an immuncompetent child. Turk J Pediatr 2018; 60: 340-343. Acanthamoeba may lead to granulomatous amebic encephalitis (GAE) with high mortality rates generally in patients with immunosupression and/or chronic disease. Here, we present a rare GAE case, who was a previously healthy child. A Georgian 9 year old boy presented with focal seizure on his left arm and confusion. Since computed tomography (CT) demonstrated hypodense lesion on right occipital lobe, brain biopsy was performed. Histopathological examination of the biopsy material revealed Acanthamoeba cysts and trophozoites together with granulomatous inflammation. The patient, who had no clinical and laboratory findings consistent with immunedeficiency, was diagnosed as GAE. He was treated with a combination drug therapy. Even if it is very rare, amebic meningoencephalitis may also be seen in immunocompetent children, as in our case. Definitive diagnosis is made by microbiological and histopathological examination of brain biopsy material.

Multiple cortical brain abscesses due to Listeria monocytogenes in an immunocompetent patient.

Listeria monocytogenes is an intracellular organism which is well recognised for its ability to cause meningeal infections in neonates, immunosuppressed, debilitated and elderly individuals. 1 Other less common central nervous system (CNS) infections caused by Listeria spp. include rhomboencephalitis, cerebritis and abscesses in the brain, brain stem and spinal cord. The neuroradiological appearance of Listeria brain abscesses is similar to other types and may also mimic primary or metastatic brain tumours. 2 , 3 We report a case of Listeria brain abscesses in a patient who was being treated for atypical parkinsonism. A good clinical outcome was achieved after appropriate antimicrobial therapy.

Encefalitis de Bickerstaff / Bickerstaff encephalitis

La encefalitis de tallo cerebral es un síndrome que se presenta con alteración del estado de conciencia, oftalmoplejia, ataxia y signos piramidales. Esta condición neurológica rara que fue descrita en 1950 por primera vez, presenta similares características clínicas a Síndrome de Guillain-Barré, por lo que representa un reto diagnóstico para el clínico. En este artículo se presenta el caso clínico de una paciente de 51 años de edad que se presenta con alteración del estado de conciencia, es llevada a unidad de cuidado intensivo de adulto donde se considera el diagnóstico de encefalitis de Bickerstaff, tras un exhaustivo abordaje diagnostico; el cual se describe, al igual que sumanejo y evolución...(AU)

Brain stem encephalitis is a syndrome that presents with altered state of consciousness, ophthalmoplegia, ataxia and pyramidal signs. This rare neurological condition that was described in1950 by The first time, it presents similar clinical characteristics to Guillain-Barré syndrome, which represents a diagnostic challenge for the clinician. This article presents the clinical case of a 51-year-old patient who presents with altered state of consciousness, is taken to the adult intensive care unit where the diagnosis of Bickerstaff encephalitis is considered, after an exhaustive diagnostic approach ; which is described, as well as its management and evolution ... (AU)

Spinal Arachnoiditis as a Complication of Cryptococcal Meningoencephalitis in Non-HIV Previously Healthy Adults.

BACKGROUND: Cryptococcus can cause meningoencephalitis (CM) among previously healthy non-HIV adults. Spinal arachnoiditis is under-recognized, since diagnosis is difficult with concomitant central nervous system (CNS) pathology. METHODS: We describe 6 cases of spinal arachnoiditis among 26 consecutively recruited CM patients with normal CD4 counts who achieved microbiologic control. We performed detailed neurological exams, cerebrospinal fluid (CSF) immunophenotyping and biomarker analysis before and after adjunctive immunomodulatory intervention with high dose pulse corticosteroids, affording causal inference into pathophysiology. RESULTS: All 6 exhibited severe lower motor neuron involvement in addition to cognitive changes and gait disturbances from meningoencephalitis. Spinal involvement was associated with asymmetric weakness and urinary retention. Diagnostic specificity was improved by MRI imaging which demonstrated lumbar spinal nerve root enhancement and clumping or lesions. Despite negative fungal cultures, CSF inflammatory biomarkers, sCD27 and sCD21, as well as the neuronal damage biomarker, neurofilament light chain (NFL), were elevated compared to healthy donor (HD) controls. Elevations in these biomarkers were associated with clinical symptoms and showed improvement with adjunctive high dose pulse corticosteroids. CONCLUSIONS: These data suggest that a post-infectious spinal arachnoiditis is an important complication of CM in previously healthy individuals, requiring heightened clinician awareness. Despite microbiological control, this syndrome causes significant pathology likely due to increased inflammation and may be amenable to suppressive therapeutics.

Toxoplasmic Encephalitis with Untreated Hairy Cell Leukemia Variant.

Toxoplasmic encephalitis is a rare infectious complication in patients with hematological malignancy except for allogeneic hematopoietic stem cell transplantation (HSCT). We herein report a case of possible toxoplasmic encephalitis with untreated hairy cell leukemia variant. Magnetic resonance imaging showed multiple nodules with surrounding edema in the entire cerebrum. A polymerase chain reaction analysis for Toxoplasma gondii was negative. Her signs and symptoms fully recovered by empirical therapy with sulfadiazine and pyrimethamine. Toxoplasmic encephalitis may occur in patients who undergo non-allogeneic HSCT for hematological malignancies, even in those who have not been treated.

A retrospective research of HIV-negative cryptococcal meningoencephalitis patients with acute/subacute onset.

Cryptococcal meningoencephalitis (CM) may present as an acute, subacute, or chronic infection. It manifests as a chronic process in over 75 % of cases, but, sometimes, it presents with a more acute onset, mostly in HIV-associated patients. Until now, there has been no study performed on the clinical features of HIV-negative CM patients with acute/subacute onset. We collected 106 HIV-negative patients diagnosed with CM in our hospital during a 15-year period, analyzed their epidemiological and clinical features, as well as the outcomes, and explored the independent prognosis factors and the factors related to the survival time among them. We found that impaired consciousness (23.4 % vs. 3.4 %, p = 0.017) was more common in CM patients with acute/subacute onset, while decreased cerebrospinal fluid (CSF) glucose (51.9 % vs. 75.9 %, p = 0.026) was less common. The ratio of CSF glucose/blood glucose [odds ratio (OR) 0.04, 95 % confidence interval (CI) 0.004-0.262, p = 0.02], impaired consciousness (OR 5.09, 95 % CI 1.477-17.522, p = 0.01), and hospitalization length (OR 0.98, 95 % CI 0.977-0.999, p = 0.04) were indicated to be not only independent prognosis factors in HIV-negative CM patients with acute/subacute onset, but also factors significantly related to the survival time. The results of our study demonstrated that the contact history and potential history risk factors would not affect the onset process of HIV-negative CM patients, and the mortality, hospitalization length, and survival time has not been related to the onset process. However, the ratio of CSF glucose/blood glucose, consciousness level, and hospitalization length of the HIV-negative CM patients with acute/subacute onset should be of greater focus in the clinical work.

Could miltefosine be used as a therapy for toxoplasmosis?

Toxoplasmosis is a zoonotic protozoal disease affecting more than a billion people worldwide. The shortfalls of the current treatment options necessitate the development of non-toxic and well-tolerated, efficient alternatives especially against the cyst form. The current study was undertaken to investigate, for the first time, the potential potency of miltefosine against Toxoplasma gondii infection in acute and chronic experimental toxoplasmosis. Results showed that there is no evidence of anti-parasitic activity of miltefosine against T. gondii tachyzoites in acute experimental toxoplasmosis. However, anti-parasitic activity of miltefosine against T. gondii cyst stage in chronic experimental toxoplasmosis could not be excluded as demonstrated by significant reduction in brain cyst burden. Moreover, considerable morphological changes in the cysts were revealed by light and electron microscopy study and also by amelioration of pathological changes in the brain. Future studies should focus on enhancement of anti-toxoplasma activity of miltefosine against chronic toxoplasmosis using formulation based nanotechnology. To the best of our knowledge, this is the first study highlighting efficacy of miltefosine against chronic toxoplasmosis, thus, increasing the list of diseases that can be targeted by this drug.

Successful treatment of toxoplasmic encephalitis diagnosed early by polymerase chain reaction after allogeneic hematopoietic stem cell transplantation: two case reports and review of the literature.

Toxoplasmic encephalitis represents a rare, but often fatal infection after allogeneic hematopoietic stem cell transplantation. Polymerase chain reaction (PCR)-based preemptive therapy is considered promising for this disease, but is not routinely applied, especially in low seroprevalence countries including Japan. We encountered 2 cases of toxoplasmic encephalitis after transplantation that were successfully treated. The diagnosis of toxoplasmic encephalitis in these cases was confirmed by PCR testing when neurological symptoms were observed. Both patients received pyrimethamine and sulfadiazine treatments within 2 weeks of the development of neurological symptoms, and remained free of recurrence for 32 and 12 months. These results emphasized the importance of the PCR test and immediate treatment after diagnosis for the management of toxoplasmic encephalitis.