A DAMP-Based Assay for Rapid and Affordable Diagnosis of Bacterial Meningitis Agents: Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae.

The rapid and accurate diagnosis of meningitis is critical for preventing severe complications and fatalities. This study addresses the need for accessible diagnostics in the absence of specialized equipment by developing a novel diagnostic assay. The assay utilizes dual-priming isothermal amplification (DAMP) with unique internal primers to significantly reduce non-specificity. For fluorescence detection, the dye was selected among Brilliant Green, Thioflavin T, and dsGreen. Brilliant Green is preferred for this assay due to its availability, high fluorescence level, and optimal sample-to-background (S/B) ratio. The assay was developed for the detection of the primary causative agents of meningitis (Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae), and tested on clinical samples. The developed method demonstrated high specificity, no false positives, sensitivity comparable to that of loop-mediated isothermal amplification (LAMP), and a high S/B ratio. This versatile assay can be utilized as a standalone test or an integrated assay into point-of-care systems for rapid and reliable pathogen detection.

Fosfomycin-Containing Regimens for the Treatment of Central Nervous System Infections in a Neonatal Intensive Care Unit: A Case Series Study.

Central nervous system infections are among the most severe infectious conditions in the neonatal period and are still burdened by significant mortality, especially in preterm infants and those with a low birth weight or other comorbidities. In this study, we examined the role of fosfomycin-containing antibiotic regimens in neonates with central nervous system infections. We included six neonates over a period of five years: four with meningitis and two with cerebral abscesses. All patients underwent fosfomycin therapy after failing first-line antibiotic regimens. Of the six neonates, two died; two developed neurological and psychomotor deficits and two recovered uneventfully. None of the neonates experienced adverse reactions to fosfomycin, confirming the safety of the molecule in this population. In conclusion, the deep penetration in the central nervous system, the unique mechanism of action, the synergy with other antibiotic therapies, and the excellent safety profile all make fosfomycin an attractive drug for the treatment of neonatal central nervous system infections.

Square the Circle: Diversity of Viral Pathogens Causing Neuro-Infectious Diseases.

Neuroinfections rank among the top ten leading causes of child mortality globally, even in high-income countries. The crucial determinants for successful treatment lie in the timing and swiftness of diagnosis. Although viruses constitute the majority of infectious neuropathologies, diagnosing and treating viral neuroinfections remains challenging. Despite technological advancements, the etiology of the disease remains undetermined in over half of cases. The identification of the pathogen becomes more difficult when the infection is caused by atypical pathogens or multiple pathogens simultaneously. Furthermore, the modern surge in global passenger traffic has led to an increase in cases of infections caused by pathogens not endemic to local areas. This review aims to systematize and summarize information on neuroinvasive viral pathogens, encompassing their geographic distribution and transmission routes. Emphasis is placed on rare pathogens and cases involving atypical pathogens, aiming to offer a comprehensive and structured catalog of viral agents with neurovirulence potential.

Role of Cefiderocol in Multidrug-Resistant Gram-Negative Central Nervous System Infections: Real Life Experience and State-of-the-Art.

Cefiderocol is a new molecule effective against multidrug-resistant (MDR) Gram-negative pathogens. Currently, there is limited evidence regarding the use of cefiderocol in central nervous system (CNS) infections. Data on the cerebrospinal fluid penetration rate of cefiderocol are limited and heterogeneous, and there is no consensus on the dosing scheme of cefiderocol to penetrate the blood-brain barrier. We present a case series and a literature review of CNS infections caused by MDR pathogens that were treated with cefiderocol: some of these patients were treated with different dose schemes of cefiderocol and underwent therapeutic drug monitoring both on plasma and cerebrospinal fluid (CSF). The CSF penetration rates and the clinical outcomes were evaluated.

Infectious Diseases of the Brain and Spine: Parasitic and Other Atypical Transmissible Diseases.

Atypical infections of the brain and spine caused by parasites occur in immunocompetent and immunosuppressed hosts, related to exposure and more prevalently in endemic regions. In the United States, the most common parasitic infections that lead to central nervous system manifestations include cysticercosis, echinococcosis, and toxoplasmosis, with toxoplasmosis being the most common opportunistic infection affecting patients with advanced HIV/AIDS. Another rare but devastating transmittable disease is prion disease, which causes rapidly progressive spongiform encephalopathies. Familiarity and understanding of various infectious agents are a crucial aspect of diagnostic neuroradiology, and recognition of unique features can aid timely diagnosis and treatment.

Empiric treatment of healthcare-associated central nervous system infections in Denmark: do we need carbapenems?

BACKGROUND: Carbapenems are widely used for empiric treatment of healthcare-associated central nervous system (CNS) infections. We investigated the feasibility of a carbapenem-sparing strategy, utilising a third-generation cephalosporin (ceftriaxone or cefotaxime) (combined with vancomycin) for the empirical treatment of healthcare-associated CNS infections in Eastern Denmark. METHODS: The departments of neurosurgery and neuro-intensive care at Copenhagen University Hospital Rigshospitalet. First, we analysed local microbiological data (1st January 2020-31st August 2022) to identify microorganisms non-susceptible to third-generation cephalosporin. Subsequently, we assessed all carbapenem prescriptions over a three-month period for their indication and justification. RESULTS: In total, 25,247 bacterial cultures were identified, of which 2,563 CNS-related, were included in the analysis. The positivity rate was 10.5% (n = 257/2439) for cerebrospinal-fluid samples and 75.8% (n = 95/124) for brain parenchyma. CNS samples from five individual patients revealed bacteria non-susceptible to third generation cephalosporins (Enterobacter spp. (n = 3), Pseudomonas spp. (n = 2), Klebsiella spp. (n = 2), Citrobacter freundii (n = 1)). All five patients had been hospitalised for ≥10days at the time-point of antibiotic therapy. Out of 11,626 sets of blood cultures, a total of 10 individual patients had Gram-negative blood-stream infections with resistance to ceftriaxone and piperacillin/tazobactam. 140 days-of-therapy (32%) with carbapenem in 18 patients (36%) were definitively or possibly indicated according to guidelines, none were indicated for healthcare-associated CNS-infections. CONCLUSION: An empiric treatment strategy relying on a third-generation cephalosporin appears suitable for healthcare-associated CNS infections at our tertiary hospital, serving a population of 2.6 million. However, in patients with prolonged hospitalization (≥10 days), immunosuppression, prior broad-spectrum antibiotic use, or history of resistant Gram-negative bacteria, empirical prescription of carbapenem may be needed.

Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients.

BACKGROUND: Early and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR). METHODS: This study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization. RESULTS: 53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0-63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 - 84.1%), 76.0% (95%CI: 56.6 - 88.5%), 77.8% (59.2 - 89.4%) and 85.2% (95%CI: 67.5 - 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay. CONCLUSIONS: NTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.

A multicenter evaluation of the QIAstat-Dx meningitis-encephalitis syndromic test kit as compared to the conventional diagnostic microbiology workflow.

PURPOSE: Rapid diagnosis and treatment of infectious meningitis and encephalitis (ME) is critical to minimize morbidity and mortality. Recently, Qiagen introduced the CE-IVD QIAstat-Dx ME panel (QS-ME) for syndromic diagnostic testing of meningitis and encephalitis. Some data on the performance of the QS-ME in comparison to the BioFire FilmArray ME panel are available. In this study, the performance of the QS-ME is compared to the current diagnostic workflow in two academic medical centers in the Netherlands. METHODS: A total of 110 cerebrospinal fluid samples were retrospectively tested with the QS-ME. The results obtained were compared to the results of laboratory-developed real-time PCR assays (LDTs), IS-pro, bacterial culture, and cryptococcal antigen (CrAg) testing. In addition, the accuracy of the QS-ME was also investigated using an external quality assessment (EQA) panel consisting of ten samples. RESULTS: Four of the 110 samples tested failed to produce a valid QS-ME result. In the remaining 106 samples, the QS-ME detected 53/53 viral targets, 38/40 bacterial targets, and 7/13 Cryptococcus neoformans targets. The discrepant bacterial results consisted of two samples that were previously tested positive for Listeria monocytogenes (CT 35.8) and Streptococcus pneumoniae (CT 40), respectively. The QS-ME detected one additional result, consisting of a varicella-zoster virus signal (CT 35.9), in a sample in which both techniques detected Streptococcus pyogenes. Finally, 100% concordance was achieved in testing a blinded bacterial ME EQA panel. CONCLUSION: The QS-ME is a relevant addition to the syndromic testing landscape to assist in diagnosing infectious ME.

Central Nervous System Tuberculosis in Immunocompromised Patients: A Case Report Emphasizing Immune Status and Early Recognition and Treatment.

Tuberculosis (TB) remains a global health challenge. Although pulmonary TB is the most frequent presentation, extrapulmonary involvement can occur, especially in immunocompromised patients. HIV-positive individuals are particularly vulnerable to opportunistic infections, such as TB, and CNS involvement is more prevalent in these patients, often leading to a poorer prognosis. CNS TB management is challenging due to nonspecific symptoms and delayed diagnosis, contributing to high mortality. It can manifest diffusely as tuberculous meningitis (TBM), localized as tuberculoma or tuberculous abscess, or as extradural and intradural spinal infections. TBM is the primary CNS manifestation, bearing significant morbidity and mortality, and rarely complicates with involvement of the spinal cord, termed tuberculous myelitis, which is associated with an unfavorable prognosis. A 61-year-old male, smoker with a history of substance abuse, undergoing seven months of antiretroviral therapy (ART) for HIV-1, presented with a two-day history of altered consciousness, sphincter incontinence, and fever. He also reported headaches, dizziness, and sleep disturbances over the past months. The examination revealed fever, asthenia, prostration, disorientation, neck rigidity, and bilateral lower limb weakness. Initial tests indicated lymphopenia, hyponatremia, and a slightly elevated C-reactive protein. Cranial CT showed no abnormalities. Lumbar puncture yielded abnormal cerebrospinal fluid (CSF), xanthochromic, hyperproteinorrheic (2316 g/L), hypoglycorrhagic (24mg/dl), with pleocytosis predominantly of mononuclear cells (98%). Compared to the values prior to ART treatment, the patient had a decreased HIV-1 viral (44 copies/ml) load but also a decreased CD4+ cell count (43 cells/mm3). Given the patient's rapid clinical deterioration, immunosuppression history, and a positive interferon-gamma release assay (IGRA) prior to ART, treatment with antituberculous drugs and dexamethasone was started at admission. Subsequently, Mycobacterium tuberculosis was identified through polymerase chain reaction (PCR) of the CSF. Cranial and spinal MRI revealed leptomeningeal enhancement from C2-C3 to the cauda equina, consistent with meningitis, without intracranial extension, and findings suggestive of myelitis, without evidence of tuberculomas or spinal cord osseous involvement. One week after treatment, the recovery of higher neurological functions became evident. Improvement in lower limb motor deficits had a delayed trajectory, with marginal progress observed at discharge. After an eight-week incubation, CSF mycobacterial culture analysis yielded negative results. This case discusses the importance of early suspicion and intervention in CNS infection prognosis. Attention to signs and symptoms beyond the most frequent ones is crucial, particularly in immunocompromised individuals like HIV patients. Identifying CSF features in different CNS infections and group-specific particulars facilitates the prompt initiation of treatment. Additionally, in co-infected patients (HIV and CNS TB), considering factors such as ART duration, CD4+ cell count, and viral load is important, in influencing the disease's incidence, course, and prognosis.

Case report: A toxoplasmic encephalitis in an immunocompromised child detected through metagenomic next-generation sequencing.

There exist numerous pathogens that are capable of causing infections within the central nervous system (CNS); however, conventional detection and analysis methods prove to be challenging. Clinical diagnosis of CNS infections often depends on clinical characteristics, cerebrospinal fluid (CSF) analysis, imaging, and molecular detection assays. Unfortunately, these methods can be both insensitive and time consuming, which can lead to missed diagnoses and catastrophic outcomes, especially in the case of infrequent diseases. Despite the application of appropriate prophylactic regimens and evidence-based antimicrobial agents, CNS infections continue to result in significant morbidity and mortality in hospital settings. Metagenomic next-generation sequencing (mNGS) is a novel tool that enables the identification of thousands of pathogens in a target-independent manner in a single run. The role of this innovative detection method in clinical pathogen diagnostics has matured over time. In this particular research, clinicians employed mNGS to investigate a suspected CNS infection in a child with leukemia, and unexpectedly detected Toxoplasma gondii. Case: A 3-year-old child diagnosed with T-cell lymphoblastic lymphoma was admitted to our hospital due to a 2-day history of fever and headache, along with 1 day of altered consciousness. Upon admission, the patient's Glasgow Coma Scale score was 14. Brain magnetic resonance imaging revealed multiple abnormal signals. Due to the patient's atypical clinical symptoms and laboratory test results, determining the etiology and treatment plan was difficulty.Subsequently, the patient underwent next-generation sequencing examination of cerebrospinal fluid. The following day, the results indicated the presence of Toxoplasma gondii. The patient received treatment with a combination of sulfamethoxazole (SMZ) and azithromycin. After approximately 7 days, the patient's symptoms significantly improved, and they were discharged from the hospital with oral medication to continue at home. A follow-up polymerase chain reaction (PCR) testing after about 6 weeks revealed the absence of Toxoplasma. Conclusion: This case highlights the potential of mNGS as an effective method for detecting toxoplasmic encephalitis (TE). Since mNGS can identify thousands of pathogens in a single run, it may be a promising detection method for investigating the causative pathogens of central nervous system infections with atypical features.

Novel anti-Acanthamoebic properties of raloxifene sulfonate/sulfamate derivatives.

Acanthamoeba are known to cause a vision threatening eye infection typically due to contact lens wear, and an infection of the central nervous system. The ability of these amoebae to switch phenotypes, from an active trophozoite to a resistant cyst form is not well understood; the cyst stage is often resistant to chemotherapy, which is of concern given the rise of contact lens use and the ineffective disinfectants available, versus the cyst stage. Herein, for the first time, a range of raloxifene sulfonate/sulfamate derivatives which target nucleotide pyrophosphatase/phosphodiesterase enzymes, were assessed using amoebicidal and excystation tests versus the trophozoite and cyst stage of Acanthamoeba. Moreover, the potential for cytopathogenicity inhibition in amoebae was assessed. Each of the derivatives showed considerable anti-amoebic activity as well as the ability to suppress phenotypic switching (except for compound 1a). Selected raloxifene derivatives reduced Acanthamoeba-mediated host cell damage using lactate dehydrogenase assay. These findings suggest that pyrophosphatase/phosphodiesterase enzymes may be valuable targets against Acanthamoeba infections.

Neurocysticercosis presenting as a locked-in lateral ventricle: A case report and evidence-based review.

Human neurocysticercosis is one of the most prevalent parasitic infestations of the central nervous system. It is considered the most frequent underlying etiology of acquired epilepsy in endemic areas in Central and South America, East Europe, Africa, and Asia, with over 50 million people affected globally. Ventricular involvement is a severe form of neurocysticercosis commonly manifests as arachnoiditis, raised intracranial pressure, or hydrocephalus, secondary to CSF flow obstruction of the ventricular system by cysts of Taenia solium, hence requiring prompt, aggressive intervention to alleviate the increased intracranial pressure to prevent imminent lethal complications. Ventricular neurocysticercosis can involve any brain ventricle but with a paramount preference for the fourth ventricle, causing non-communicating hydrocephalus and symmetric ventriculomegaly. However, in this clinical report, we present an uncommon case of trapped (locked-in) lateral ventricle caused by an isolated cysticercus trapped at the ipsilateral foramen of Monro, which is an atypical location for neurocysticercosis, adding more challenges to diagnosis and during the process of surgical extraction. We additionally provide a comprehensive, evidence-based review of the clinical course and management options relevant to the entity of ventricular neurocysticercosis, besides recent relevant clinical updates.

The epidemiology, clinical presentation and treatment outcomes in CNS actinomycosis: a systematic review of reported cases.

BACKGROUND: CNS actinomycosis is a rare chronic suppurative infection with non-specific clinical features. Diagnosis is difficult due to its similarity to malignancy, nocardiosis and other granulomatous diseases. This systematic review aimed to evaluate the epidemiology, clinical characteristics, diagnostic modalities and treatment outcomes in CNS actinomycosis. METHODS: The major electronic databases (PubMed, Google Scholar, and Scopus) were searched for the literature review by using distinct keywords: "CNS" or "intracranial" or "brain abscess" or "meningitis" OR "spinal" OR "epidural abscess" and "actinomycosis." All cases with CNS actinomycosis reported between January 1988 to March 2022 were included. RESULTS: A total of 118 cases of CNS disease were included in the final analysis. The mean age of patients was 44 years, and a significant proportion was male (57%). Actinomycosis israelii was the most prevalent species (41.5%), followed by Actinomyces meyeri (22.6%). Disseminated disease was found in 19.5% of cases. Most commonly involved extra-CNS organs are lung (10.2%) and abdomen (5.1%). Brain abscess (55%) followed by leptomeningeal enhancement (22%) were the most common neuroimaging findings. Culture positivity was found in nearly half of the cases (53.4%). The overall case-fatality rate was 11%. Neurological sequelae were present in 22% of the patients. On multivariate analysis, patients who underwent surgery with antimicrobials had better survival (adjusted OR 0.14, 95% CI 0.04-0.28, p value 0.039) compared to those treated with antimicrobials alone. CONCLUSION: CNS actinomycosis carries significant morbidity and mortality despite its indolent nature. Early aggressive surgery, along with prolonged antimicrobial treatment is vital to improve outcomes.

Novel Anti-Acanthamoebic Activities of Irosustat and STX140 and Their Nanoformulations.

Pathogenic Acanthamoeba produce keratitis and fatal granulomatous amoebic encephalitis. Treatment remains problematic and often ineffective, suggesting the need for the discovery of novel compounds. For the first time, here we evaluated the effects of the anticancer drugs Irosustat and STX140 alone, as well as their nanoformulations, against A. castellanii via amoebicidal, excystment, cytopathogenicity, and cytotoxicity assays. Nanoformulations of the compounds were successfully synthesized with high encapsulation efficiency of 94% and 82% for Irosustat and STX140, respectively. Nanoparticles formed were spherical in shape and had a unimodal narrow particle size distribution, mean of 145 and 244 nm with a polydispersity index of 0.3, and surface charge of -14 and -15 mV, respectively. Irosustat and STX140 exhibited a biphasic release profile with almost 100% drug released after 48 h. Notably, Irosustat significantly inhibited A. castellanii viability and amoebae-mediated cytopathogenicity and inhibited the phenotypic transformation of amoebae cysts into the trophozoite form, however their nanoformulations depicted limited effects against amoebae but exhibited minimal cytotoxicity when tested against human cells using lactate dehydrogenase release assays. Accordingly, both compounds have potential for further studies, with the hope of discovering novel anti-Acanthamoeba compounds, and potentially developing targeted therapy against infections of the central nervous system.

Post-neurosurgical Nocardia meningoventriculitis: a case report and review of the literature.

The genus Nocardia consists of a group of gram-positive environmental bacteria. They typically cause lung and brain infections in immunocompromised patients, even though one out of three infected patients have a normally functioning immune system. Being a ubiquitous microorganism, in some cases Nocardia has been associated with nosocomial acquired infections and surgical procedures. A review of the literature in this field follows the case report. A 47-year-old woman underwent an endoscopic third ventriculostomy and a left retro-sigmoid craniotomy for a schwannoma removal. Meningeal symptoms began a week later, in association with C reactive protein rise and leukocytosis. Cerebrospinal fluid (CSF) examination was clear with hypoglycorrhachia, hyperprotidorrachia and polymorphonuclear cells. Cultural exam was negative. At the brain magnetic resonance imaging (MRI) purulent material was described in the occipital ventricular horns. Empirical broad spectrum antibiotic therapy was given for 31 days until the brain MRI showed a resolution of the infection. Ten days later, the patient was admitted to the hospital because of new meningeal symptoms. Cerebrospinal fluid culture and Polymerase-chain reaction (PCR) Multiplex for the most important meningitis viruses and bacteria tested negative. A broad-spectrum antibiotic therapy was started with no benefit; thus, a broad-spectrum antifungal therapy was added with little success on clinical status. Meanwhile, a 16s and 18s rRNA PCR was executed on a previous Cerebrospinal fluid with negative results, excluding bacterial and fungal infections. For this reason, all the therapies were stopped. After a few days, high fever and meningeal signs reappeared. The brain MRI showed a meningoventriculitis. An Ommaya catheter with reservoir was inserted and the drawn CSF resulted in the growth of Nocardia farcinica. Antibiogram-based antibiotic therapy was started with intravenous imipenem and trimethoprim-sulfamethoxazole, showing clinical benefit. The patient was sent home with oral linezolid and amoxicillin/clavulanate for a total of 12 months of therapy. Nocardia rarely causes post-neurosurgical complication in a nosocomial setting. This case shows the difficulty in detecting Nocardia and the importance of the correct microbiological sample and antibiogram-based antibiotic therapy to achieve successful treatment.

Long-tunneled versus short-tunneled external ventricular drain: a quasi-experimental study in a cohort of pediatric patients.

OBJECTIVE: The primary aim of this study was to compare external ventricular drain (EVD)-related infection rates and mechanical complications between long-tunneled EVDs (LTEVDs) with an interposed valve and short-tunneled EVDs (STEVDs) in a cohort of pediatric patients. The second objective was to compare hospital resources used for LTEVDs versus STEVDs in the same cohort of patients and the same study period. METHODS: The study consisted of a quasi-experimental investigation comparing a prospective group of patients who received LTEVDs with a retrospective (historic) cohort of patients treated with STEVDs. The prospective nonrandomized quasi-experimental protocol of the LTEVD cohort included patients who needed an EVD for more than 3 days. Data were recorded prospectively as the patients were added to the study, until reaching the sample size established by the protocol. The comparison group of the STEVD cohort was retrospectively collected from patients' records. Patients were included consecutively, from newest to oldest, starting with the last STEVD inserted at the authors' hospital until reaching the sample size established in the protocol. The inclusion and exclusion criteria for both groups were the same. RESULTS: One hundred thirty-four patients were included in this quasi-experimental study; there were 67 in each group. LTEVDs reduced the odds of having an EVD-related infection by 92% (OR 0.08, 95% CI 0.01-0.39; p = 0.002). Compared to STEVDs, the LTEVDs reduced by 69% the odds of having a CSF leak (OR 0.31, 95% CI 0.10-0.91; p = 0.03). Neither CSF blockage (OR 0.12, 95% CI 0.01-1.08; p = 0.06) nor displacement (OR 0.73, 95% CI 0.15-3.43; p = 0.69) showed a statistically significant difference between groups. More resources were allocated to STEVDs than to LTEVDs in most areas considered in this study. CONCLUSIONS: Compared to STEVDs, LTEVDs are a cost-effective and safe method to reduce EVD-related infection rates and other complications in pediatric patients. The authors believe that reducing the infection rate and complications and giving the patient more independence outweighs the additional costs that this new technique may entail.

Antiamoebic Properties of Ceftriaxone and Zinc-Oxide-Cyclodextrin-Conjugated Ceftriaxone.

Acanthamoeba castellanii is a ubiquitous free-living amoeba capable of instigating keratitis and granulomatous amoebic encephalitis in humans. Treatment remains limited and inconsistent. Accordingly, there is a pressing need for novel compounds. Nanotechnology has been gaining attention for enhancing drug delivery and reducing toxicity. Previous work has shown that various antibiotic classes displayed antiamoebic activity. Herein, we employed two antibiotics: ampicillin and ceftriaxone, conjugated with the nanocarrier zinc oxide and ß-cyclodextrin, and tested them against A. castellanii via amoebicidal, amoebistatic, encystment, excystment, cytopathogenicity, and cytotoxicity assays at a concentration of 100 µg/mL. Notably, zinc oxide ß-cyclodextrin ceftriaxone significantly inhibited A. castellanii growth and cytopathogenicity. Additionally, both zinc oxide ß-cyclodextrin ceftriaxone and ceftriaxone markedly inhibited A. castellanii encystment. Furthermore, all the tested compounds displayed negligible cytotoxicity. However, minimal anti-excystment or amoebicidal effects were observed for the compounds. Accordingly, this novel nanoconjugation should be employed in further studies in hope of discovering novel anti-Acanthamoeba compounds.

Viral aetiology of acute central nervous system infections in children, Iran.

Introduction. Viral infections are increasingly an important cause of central nervous system (CNS) complications.Hypothesis/Gap Statement. There is no comprehensive insight about CNS infections due to viral agents among Iranian children.Aim. This study aimed to investigate the viral aetiology, clinical and epidemiological profile of children with acute infections of the CNS.Methodology. A prospective study was conducted on children at the referral hospital in Isfahan, Iran, from June 2019 to June 2020. A multiplex PCR assay was used to detect the viral causative agent in cerebrospinal fluid and throat/rectal swab samples.Results. Among 103 patients with eligible criteria, a confirmed or probable viral aetiology was detected in 41 (39.8 %) patients, including enteroviruses - 56.1 %, herpes simplex virus 1/2 (HSV-1/2) - 31.7 %, Epstein-Barr virus - 17.1 %, varicella-zoster virus (VZV) - 9.7 %, influenza A virus (H1N1) -4.9 % and mumps - 2.4 %. There was a higher proportion of PCR-positive samples in infants than in other age groups. Encephalitis and meningoencephalitis were diagnosed in 68.3 % (28/41) and 22 % (9/41) PCR-positive cases, respectively.Conclusion. The findings of this research provide insights into the clinical and viral aetiological patterns of acute CNS infections in Iran, and the importance of molecular methods to identify CNS viruses. HSV and VZV were identified as important causes of encephalitis in young children.

Caregiver's perspectives on the Central Nervous System infection illness trajectory among older persons with dementia in Northern Uganda-a qualitative community-based study.

BACKGROUND: Few studies have explored the Central Nervous System (CNS) infection illness trajectory among older persons with dementia in sub-Saharan African (SSA) settings. This study explored the Caregiver's perspectives on the Central Nervous System infection illness trajectory among the older persons with dementia in Northern Uganda. METHODS: This was a qualitative study conducted in Lira District northern Uganda in March 2022 amongst purposively selected 20 caregivers of the older persons aged 50 + years with a positive history of CNS infection and later life dementia. Data were collected using an in-depth interview guide. Audio recordings and field notes of the interviews were undertaken. The interviews generated data on the CNS infection illness trajectory from onset to the current demented state of the older persons. The audio-recorded interviews were transcribed verbatim before manual reflective thematic analysis. RESULTS: Older persons with a positive history of CNS infection illness and later life dementia in rural northern Uganda presented with symptoms of early life CNS infection illness ranging from neck pain, back pain, chronic headache, and fatigue. There were also manifestations of comorbidities particularly road traffic accidents involving traumatic injury to the head, neck, and spine, high blood pressure, chronic headache, and or their medications in the older person's trajectory to later life dementia. A plurality of healthcare which included both formal and informal healthcare medicines was sought and utilized for the treatment and care of the CNS infection illness and dementia by the older persons amidst improper diagnosis and mismanagement. CONCLUSIONS AND RECOMMENDATIONS: Older persons with early-life CNS infections illness and later-life dementia were reported to present with symptoms including neck pain, back pain, chronic headache, high blood pressure, and fatigue. The reported symptoms of CNS infection illness may be intertwined with co-morbidities particularly traumatic injury involving the head, neck, and spine, high blood pressure, and chronic headache. Healthcare professionals should integrate routine screening of older persons for the history of CNS infections, chronic headache, high blood pressure, trauma to the head, neck, and spine, and dementia and early treatment.

Oligoclonal bands: An immunological and clinical approach.

Oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) represent an indicator of IgG and IgM immunoglobulins intrathecal synthesis in the central nervous system (CNS). The techniques and detection methods for their determination have evolved from the beginning to isoelectric focusing on an agarose gel as the gold standard technique and immunodetection as the reference method. The evolution, both in techniques and methods for detection of IgG and IgM OCBs is evaluated in this review. In addition to the significance of the presence of a single band of IgG immunoglobulin in CSF, IgG OCBs within the diagnostic criteria of multiple sclerosis (MS), the prevalence of IgG OCBs and the effect of latitude in MS, as well as the clinical and immunological involvement of OCBs (IgG and IgM) in MS and other neurological diseases.