Central Nervous System Infection Research Articles

Outcomes of Invasive Fungal Infections Treated with Isavuconazole: A Retrospective Review

Background: Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications. Methods: We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized. Results: The majority of patients were immunocompromised (n = 76, 58%). ISA was used primarily as a secondary therapy (n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi (n = 19, 15%) as well as central nervous system (CNS) infections (n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57–73% response rate). Conclusions: We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections.

Particularities of spasticity in myelomeningocele patients.

Myelomeningocele (MMC), a congenital neural tube defect, is the most common developmental anomaly of the central nervous system (CNS). Spasticity is among the main disabling factors in these patients, affecting up to 1/5 of children. The purpose of this article is to review the current knowledge regarding spasticity in MMC patients, mainly focusing on its manifestations and management. A literature search was conducted using the PubMed database for the terms "myelomeningocele" and "spasticity." Data were collected by 5 independent investigators and then synthesized in a scoping format. Causes of spasticity in these patients include hydrocephalus, tethered cord syndrome (TCS), syringomyelia, CNS infection, and associated congenital brain and spine anomalies. Clinical manifestations include limb spasticity and neurogenic bladder. Spasticity primarily affects muscles below the neurological level and contributes to gait impairment. Besides walking ability, spasticity also severely affects functional mobility in general, self-care, and quality of life. The majority of MMC patients experience neurogenic bladder. Treatment of spasticity can be symptomatic or target its cause. Medical and surgical options are available for both limb and bladder spasticity. Regular physiotherapy and orthotics are used to prevent contractures and the early introduction of orthoses is the cornerstone of a gait training program. Neurosurgical treatment options for spasticity include nonablative and ablative procedures such as selective dorsal rhizototmy. The urodynamic pattern guides treatment strategies, with intermittent catheterization being the best treatment option for patients with underactive detrusor and overactive sphincter muscles. Given the particularities of spasticity in MMC patients, a multidisciplinary team approach and early rehabilitation programs are keys for their optimal management.

Life Quality of Pediatric Patients with Central Nervous System Infections: A 1-Year Follow-up

Background: Central nervous system (CNS) infections can lead to long-term motor and cognitive complications in children. Objectives: We aimed to investigate the prevalence of attention deficit-hyperactivity disorder (ADHD) and assess the quality of life in children with CNS infections. Methods: A longitudinal study was conducted on 94 children (aged 6 - 15 years) with CNS infection symptoms who were admitted to referral hospitals in Isfahan, Iran. Parents completed questionnaires assessing quality of life and neurological deficits at 6 and 12 months after discharge. All patients were evaluated by the corresponding physician for a final assessment. Results: Attention deficit-hyperactivity disorder symptoms were diagnosed in 30 patients, with viral encephalitis being the most common infection. The quality of life in children with CNS infections was significantly lower compared to that of healthy children. Conclusions: Central nervous system infections negatively impact the quality of life in children. Screening for ADHD and managing affected children can help improve outcomes. Further research and interventions are needed to mitigate long-term complications.

Characterization of neurologic disease-associated Streptococcus suis strains within the United States swine herd and use of diagnostic tools.

Streptococcus suis negatively impacts swine health, posing diagnostic and preventative challenges. S. suis can induce disease and also quietly reside on mucosal surfaces. The limited use of diagnostic tools to identify disease-associated strains and rule out differential diagnoses, alongside the complex ecology of S. suis, poses significant challenges in comprehending this important pathogen and defining pathotypes. This study evaluated 2,379 S. suis central nervous system (CNS) isolates from diagnostic submissions between 2015 and 2019. Isolates originating from submissions with histologic evidence of CNS infection (n = 1,032) were further characterized by standard and advanced diagnostic techniques. We identified 29 S. suis serotypes and 4 reclassified serotypes as putative causes of CNS disease. Among these, serotypes 1 and 7 emerged as the predominant putative causes of CNS infection (32% of submissions). Furthermore, 51 sequence types (STs), of which 15 were novel, were detected with ST1 predominating. Through whole-genome sequencing of 145 isolates, we observed that five commonly used virulence-associated genes (VAGs; epf, mrp, sly, ofs, and srtF) were not present in most disease-associated isolates, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) yielded false-positive results in 7% of isolates. These data indicate that (i) clinical signs and site of isolation alone are insufficient for defining a pathotype, (ii) S. suis serotypes and STs associated with CNS infection are more diverse than previously reported, (iii) MALDI-TOF MS may need to be supplemented with additional diagnostic tools for precise S. suis identification, and (iv) VAGs remain an unreliable means for identifying isolates associated with CNS disease.IMPORTANCEStreptococcus suis is an important and complex systemic bacterial pathogen of swine. Characterization of S. suis strains originating from pigs with histologic confirmation of neurologic disease is limited. Review of swine diagnostic submissions revealed that fewer than half of cases from which S. suis was isolated from the brain had histologic evidence of neurologic disease. This finding demonstrates that clinical signs and site of isolation alone are not sufficient for identifying a neurologic disease-associated strain. Characterization of strains originating from cases with evidence of disease using classic and advanced diagnostic techniques revealed that neurologic disease-associated strains are diverse and commonly lack genes previously associated with virulence.

Childhood cerebral malaria: Pattern of biochemical parameters and clinical outcome in a Nigerian tertiary hospital

BackgroundThe outcome of children with cerebral malaria involves an interplay of factors including clinical and biochemical parameters, a deep knowledge of these laboratory biochemical parameters is essential. Thus, this study aimed to assess the pattern of the biochemical parameters in children with cerebral malaria and how it may affect the clinical outcomes. MethodsA prospective observational cohort study among fifty subjects at the children's emergency unit. The participants were children aged 6 months to 12 years admitted with a history of fever and altered sensorium, demonstrable malaria parasite in the blood film and cerebrospinal fluid (CSF) analysis not suggestive of central nervous system (CNS) infections. Detailed history was taken with thorough examinations of each child. Samples were collected for malaria parasites, serum electrolytes, urea, creatinine, and blood glucose values. The clinical outcomes were correlated with the analyte levels. Results60 % of the children survived without any sequelae with the highest proportion (70 %) of survivors being children above five years. Children with hypoglycemia had a 3.5-fold higher risk of poor outcomes and this is statistically significant (RR = 3.65 p = 0.014). Hyperkalaemia was significantly associated with poor outcomes (RR = 2.57, p = 0.009). Subjects with hypochloraemia had three times the risk of poor outcome and mortality with statistically significant association (RR = 3.07, χ2 = 8.519, p = 0.004). There was a significant association between metabolic acidosis and poor clinical outcome. (RR = 1.99, χ2 = 4.089, p = 0.043). The parasite density was significantly associated with the serum bicarbonate (HCO3−) and Chloride, p-value < 0.05. ConclusionHypoglycaemia, hyperkalemia, hypochloremia and metabolic acidosis were significantly associated with poor outcomes, thus, good predictors of clinical outcomes in children diagnosed with cerebral malaria. Periodic evaluation and monitoring of these parameters is essential for prompt intervention to forestall devastating outcomes.

Brain abscess caused by Nocardia farcinica in a person living with HIV

Nocardia farcinica is the most pathogenic Nocardia, which is easy to disseminate. It can be caused by trauma, and even lead to severe lung or central nervous system infection. This report covers a case of Nocardia brain abscess in an HIV patient, who underwent resection of the brain abscess, followed by anti-infective therapy with sulfamethoxazole and meropenem, and eventually made a good recovery. The mortality rate of Nocardia farcinica brain abscess has been attributed to the severity of the underlying disease, the difficulty in identifying the pathogen, and its inherent resistance to antibiotics, leading to inappropriate or late initiation of treatment. Medication should follow the principle of sufficient dosage and sufficient course of treatment.

Acute Approach to Central Nervous System Infections in Kazakhstan

Background Neuroinfections in children are a socially significant problem of our time, as they can lead to disability and death of the patient, which actualizes the need for their early clinical diagnosis. The purpose of the study: to identify patterns of clinical manifestations of central nervous system lesions in children with neuroinfections. Materials and methods The cases of neuroinfections in 101 children treated at the “City Clinical Infectious Diseases Hospital” (Shymkent) in the period from 2018 to 2022 were analyzed, of which 37 patients with viral neuroinfections, 64 with bacterial ones. Results The predominance of bacterial neuroinfections over viral ones was revealed, with a predominance among young boys. Headache or its equivalents (in children under one year old) were observed in 72.5%; most often in children with viral infections of the nervous system (81.2%), less often in patients with bacterial infections (65.4%), p 0.01. In most cases, the disease manifested with the phenomena of fever and vomiting. When assessing the neurological status, the duration of preservation of two frequently occurring meningeal signs (rigidity of the occipital muscles, Kernig’s symptom) was taken into account, which was 6 ± 1.3 days and 5 ± 1.1 days in the group with bacterial neuroinfections, and 4 ± 1.8 and 5 ± 1.7 days, respectively, in the group with viral neuroinfections (p 0.05). With pneumococcal etiology, the most severe and protracted cases of the course of neuroinfections are recorded. Frequent emergency conditions in infectious lesions of the central nervous system in the form of cerebral edema, septic shock, which occur more often in bacterial neuroinfections, have been identified. Conclusion Neuroinfections are characterized by a symptom complex of clinical manifestations, which should be interpreted by doctors in a timely and correct manner in order to diagnose early and minimize adverse outcomes of the disease. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1206-1212

Blood-brain barrier damage accelerates the accumulation of micro- and nanoplastics in the human central nervous system

The widespread use of plastics has led to increased micro- and nanoplastics (MNPs) pollution, resulting in significant environmental challenges and concerns about potential harm to human health. This study investigated whether certain types of MNPs can accumulate in the human central nervous system (CNS) and trigger inflammatory responses, particularly after CNS infection. Our analysis of 28 cerebrospinal fluid (CSF) samples from 28 patients with or without CNS infection revealed that only polystyrene (PS), polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC) were capable of selectively entering the human CNS. Concentrations of PP and PE were positively correlated with the CSF albumin index. The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly increased in patients with CNS infections. However, concentrations of MNPs were not significantly associated with CSF levels of IL-6 or IL-8. Overall, these findings suggest that specific MNPs can penetrate the human CNS, especially after impairment of the blood-brain barrier. Notably, MNPs derived from commonly used plastics did not significantly induce or exacerbate inflammation in the human CNS.

Acute infections of the central nervous system in children and adults: diagnosis and management.

Central nervous system infections are due to different microorganisms such as viruses, bacteria, mycobacteria, fungi, amoebas, and other parasites. The etiology depends on multiple risk factors, and it defines the infection location because some microorganisms prefer meninges, brain tissue, cerebellum, brain stem or spinal cord. The microorganisms induce diseases in the nervous system through direct invasion, neurotoxin production, and the triggered immune response. To determine the infection etiology, there are several diagnostic tests which may be conducted with cerebrospinal fluid, blood, respiratory and stool samples. These tests include but are not limited to direct microscopic examination of the sample, stains, cultures, antigenic tests, nucleic acid amplification tests, metagenomic next-generation sequencing, immunologic biomarker and neuroimaging, especially contrast-enhanced magnetic resonance imaging. The treatment may consist of specific antimicrobial treatment and supportive standard care. Since viruses have no specific antiviral treatment, antimicrobial treatment is mainly targeted at non-viral infections. This article will focus on diagnosis and treatment of acute acquired infections of the central nervous system beyond the neonatal period. The discussion defines the disease, provides the clinical presentation, explains the etiology and risk factors, and briefly mentions potential complications. This updated review aims to provide the reader with all the elements needed to adequately approach a patient with a central nervous system infection. Mycobacterium tuberculosis infection, Cryptococcus spp. infection and vaccines are not within the scope of this article.

A narrative review of magnetic resonance imaging findings in pediatric idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a rare neurological disorder in the pediatric population which is defined as an increase in intracranial pressure (ICP) without the presence of brain parenchymal lesions, hydrocephalus, or central nervous system infection. In this study, we have determined the magnetic resonance imaging (MRI) findings in IIH patients. A comprehensive literature search was conducted using the electronic databases including Web of Sciences, Scopus, and Pubmed to identify suitable and relevant articles using keyword search methods. The search included keywords such as "idiopathic intracranial hypertension," "pseudotumor cerebri," "MRI," and "pediatrics." The search was limited to the available publications up to January 2024. MRI plays a crucial role in diagnosing IIH by excluding secondary causes and revealing neuroimaging findings associated with elevated ICP. Despite fewer studies in children compared to adults, MRI serves as a cornerstone in identifying traditional neuroradiological markers such as empty sella turcica, posterior globe flattening, optic nerve tortuosity, optic nerve sheath distension, and transverse venous sinus stenosis. Additional subtle markers include increased Meckel's cave length, cerebellar tonsillar herniation, and slit-like ventricles, although these are less reliable. Diffusion-weighted imaging does not typically show cerebral ADC value changes indicative of cerebral edema in pediatric IIH. MRI findings provide valuable non-invasive diagnostic indicators that facilitate early detection, clinical management, and potential surgical intervention in pediatric IIH. The reliability of these MRI markers underscores their importance in clinical practice.

Meningomyelocele defect report: surgical technique selection

Aims: Surgical repair of meningomyelocele is important in terms of infection, cerebrospinal fluid (CSF) leakage, and preservation of neural structures. While there are numerous techniques available for repair, there are few guidelines on when flap repair should be performed. In this study, we employed a method to select the surgical technique. Methods: Thirty-two patients with meningomyelocele who underwent surgery were included in the study. The decision to use or not to use a flap was based on the ratio of defect height to width and the ratio of the axillary line to defect width. Results: Fasciocutaneous transposition flap (FTF) repair was performed in 17 patients, whereas primary repair was performed in 15 patients. There was no statistically significant difference between the groups in terms of preoperative characteristics of the patients. In the FTF group, one patient experienced necrosis at the wound site, and one patient developed a cerebrospinal fluid fistula. In the primary repair group, necrosis was observed in one patient, CSF fistula developed in two patients, and central nervous system infection developed in one patient. No statistically significant difference was found between the groups in terms of complications. Conclusion: The results obtained in the present study suggest that the shape of the defect and the ratio of intact tissue to defect size are more important than the size of the defect itself in achieving appropriate tension during repair. By employing the patient selection guidelines we achieved successful outcomes using a different flap technique.

Sarcopenia Predicts the Development of Early Adjacent Segment Disease After Transforaminal Lumbar Interbody Fusion.

Predicting the development of adjacent segment disease (ASD) after lumbar spine fusion would help guide preoperative and postoperative therapies to prevent reoperation. We sought to evaluate whether sarcopenia predicts the development of early ASD after transforaminal lumbar interbody fusion (TLIF). Retrospective data were collected from 109 patients who underwent TLIF from 2013 to 2023. Patients older than 18 years who underwent elective posterior midline approach TLIF were included. Patients with prior lumbar instrumented fusions, cases of trauma, central nervous system infection, cancer, or long-construct thoracolumbar deformity corrections and those who lacked sufficient follow-up were excluded. The primary outcome was radiographic ASD development within 3 years of surgery. Psoas volumetric measurements were recorded from the most recent preoperative MRI. Odds ratios were calculated with logistic regression analyses. In 109 patients undergoing elective TLIF, 22 (20.2%) developed ASD within 3 years. Gender, body mass index, and extent of surgery were not associated with ASD development. Multivariate analysis showed left/right psoas cross-sectional area, and psoas:vertebral body ratio (P:VBR) predicted early ASD (P < .0001). Sarcopenia was further categorized as having bilateral P:VBR ≥1 SD below gender mean (T-score -1). Of 18 sarcopenic patients, 15 developed early ASD (83.33%) vs 7 of 91 nonsarcopenic patients (7.69%; P < .0001). Postoperative mismatch between pelvic incidence and lumbar lordosis was predictive of ASD on univariate (P = .0480) but not multivariate analysis. Pelvic tilt and lumbar lordosis postoperatively were not associated with early ASD. Sarcopenia, measured by decreased psoas area and P:VBR, predicts ASD formation within 3 years of surgery. Morphometric analysis of psoas size is a simple tool to identify patients at risk of developing ASD. This information can potentially guide preoperative and postoperative therapies, affect surgical decision making, and effectively counsel patients on risks of reoperation.

Sialic acid and PirB are not required for targeting of neural circuits by neurotropic mammalian orthoreovirus.

Serotype 3 (T3) strains of mammalian orthoreovirus (reovirus) spread to the central nervous system to infect the brain and cause lethal encephalitis in newborn mice. Although reovirus targets several regions in the brain, susceptibility to infection is not uniformly distributed. The neuronal subtypes and anatomic sites targeted throughout the brain are not precisely known. Reovirus binds several attachment factors and entry receptors, including sialic acid (SA)-containing glycans and paired immunoglobulin-like receptor B (PirB). While these receptors are not required for infection of some types of neurons, reovirus engagement of these receptors can influence neuronal infection in certain contexts. To identify patterns of T3 neurotropism, we used microbial identification after passive tissue clearance and hybridization chain reaction to stain reovirus-infected cells throughout intact, optically transparent brains of newborn mice. Three-dimensional reconstructions revealed in detail the sites targeted by reovirus throughout the brain volume, including dense infection of the midbrain and hindbrain. Using reovirus mutants incapable of binding SA and mice lacking PirB expression, we found that neither SA nor PirB is required for the infection of various brain regions. However, SA may confer minor differences in infection that vary by region. Collectively, these studies indicate that many regions in the brain of newborn mice are susceptible to reovirus and that patterns of reovirus infection are not dependent on reovirus receptors SA and PirB.IMPORTANCENeurotropic viruses invade the central nervous system (CNS) and target various cell types to cause disease manifestations, such as meningitis, myelitis, or encephalitis. Infections of the CNS are often difficult to treat and can lead to lasting sequelae or death. Mammalian orthoreovirus (reovirus) causes age-dependent lethal encephalitis in many young mammals. Reovirus infects neurons in several different regions of the brain. However, the complete pattern of CNS infection is not understood. We found that reovirus targets almost all regions of the brain and that patterns of tropism are not dependent on receptors sialic acid and paired immunoglobulin-like receptor B. These studies confirm that two known reovirus receptors do not completely explain the cell types infected in brain tissue and establish strategies that can be used to understand complete patterns of viral tropism in an intact brain.

Effectiveness of combination therapy with intrathecal or intraventricular administration of polymyxin B for hospital-acquired central nervous system infections caused by carbapenem-resistant Acinetobacter baumannii: a retrospective study

To evaluate the therapeutic regimen, efficacy and safety of intrathecal or intraventricular (ITH/IVT) administration of polymyxin B for hospital-acquired central nervous system (CNS) infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). A retrospective study was performed on patients with CNS infections caused by CRAB treated with ITH/IVT combination therapy. The primary study outcome was the clinical efficacy after treatment. Secondary outcomes were bacterial clearance rate and safety of therapy. In total, 35 patients who received ITH (13[37.1%]) or IVT (22[62.9%]) polymyxin B as combination therapy were included. The median duration of ITH/IVT polymyxin B therapy was 9 days (interquartile ranges, 7-11). The overall clinical cure and bacterial clearance rate was 77.1% and 85.7%, respectively. No adverse effects deemed related with ITH/IVT polymyxin B were recorded. Clinical failure was independently associated with the initial Acute Physiology and Chronic Health Evaluation II (≥ 15) (odds ratio [OR], 1.24; 95% confidence interval [CI]: 1.05-1.42; P = 0.038) and Glasgow Coma Scale scores (≤ 8) (OR, 0.69; 95% CI: 0.49-0.88; P = 0.029). Early administration (within 4 days) of ITH/IVT polymyxin B therapy can support significantly higher clinical cure rate (OR, 0.65; 95% CI: 0.49-1.12; P < 0.001), and potentially reduce the length of treatment and the adverse effects. ITH/IVT administration of polymyxin B is a valid alternative for the treatment of CNS infections caused by CRAB. Early use of ITH/IVT polymyxin B can lead to higher clinical success.

Filum terminale infected epidermoid cysts in pediatric age group; A case series

BackgroundEpidermoid cysts are rare and account for only 1 % of primary spinal tumors. It's due to inclusion of ectodermal tissue during the third and fourth weeks of gestation. Infected epidermoid cysts are exceedingly rare with very few reports in literature. The clinical presentations include radicular symptoms, motor weakness, sphincteric disturbance, and repeated chemical meningitis. Surgery of this kind of tumor remained a challenge and of a considerable recurrence rate. MethodsThis is a retrospective study reviewing the records of six children who were treated for filum terminale infected epidermoid cysts. All patients underwent microsurgery, and the surgical outcomes were studied through a follow up period of at least 24 months. ResultsAll children had a low back dermal sinus with purulent discharge. One child was a recurrent presentation after the previous two surgeries for evacuation of pus collection, and the other five children were operated for the first time. All the six children had an associated neurological deficit; one child presented with active central nervous system infection, and one child had a history of meningitis and admission to hospital prior to our surgery. Regular follow up revealed no recurrence in any of the six patients. The five patients, who presented with motor weakness, showed significant improvement of the motor power with regular post-operative physical therapy. ConclusionEpidermoid cysts are rare benign lesions that may lead to significant morbidity when infected. The aim of microsurgical excision is to remove the cyst content and its capsule without inducing or increasing neurological deficit by the aid of intraoperative neuromonitoring and microsurgery techniques.

Cerebrospinal fluid lactate levels as a prognostic indicator in HIV-negative patients with cryptococcal meningitis: a retrospective cohort study

Abstract Background Cryptococcal meningitis (CM) is a severe central nervous system infection. In patients with human immunodeficiency virus (HIV) infections and coexisting CM, elevated baseline cerebrospinal fluid (CSF) lactate levels can predict increased mortality. However, the CSF lactate level’s significance in HIV-negative patients with CM remains unclear, necessitating further investigation to elucidate the potential distinctions and enhance patient management. This study investigated the CSF lactate level significance in HIV-negative patients with CM. Methods This retrospective study utilized data from the clinical databases of patients who underwent lumbar punctures at a medical center in Kaohsiung City, Southern Taiwan. Demographic data, CSF lactate levels, routine CSF analyses, and hematological and neurological findings were evaluated. The optimal CSF lactate threshold value was determined using the Youden index. Results This retrospective study included 70 patients with CM, among whom 44 (63%) and 26 (37%) tested negative and positive for HIV, respectively. The group without HIV exhibited higher CSF lactate levels, with an optimal CSF lactate cut-off point for predicting 90-day mortality of 7.935 mmol/L, resulting in significant predictive accuracies (area under the curve, 0.755; sensitivity, 57.1%; specificity, 100%); this value was an independent mortality predictor in HIV-negative patients. In HIV-negative patients with CM, CSF lactate levels ≥7.935 mmol/L correlated with higher mortality rates but without statistical significance. All HIV-negative patients with CM and CSF lactate levels ≥7.935 mmol/L died within 3 months of admission. Conclusions HIV-negative patients with CM had elevated CSF lactate levels that correlated with adverse outcomes, enabling early identification of high-risk individuals.

Causes of Pediatric Deaths in Lusaka, Zambia: A Quantitative Geographic Information Systems Approach.

While childhood mortality has been declining in Zambia, it remains high at 58 per 1000 live births. Importantly, many leading causes of mortality in Zambia are preventable. This study was conducted to identify clusters of childhood mortality, causes of death of recently deceased children, barriers to care, and risk factors for mortality in Lusaka, Zambia. This study was conducted as a prospective cohort study. Family members or lawfully authorized representatives (LARs) were interviewed when they came to pick up death certificates for recently deceased children from Lusaka Children's Hospital. Each interview included a verbal autopsy, determination of the child's location of residence, and collection of demographic information. Demographic data was also collected from a healthy control group. Quantitative Geographic Information Systems was used to visualize mortality and evaluate for clustering. Leading primary causes of death included malnutrition (21%), complications of chronic illnesses (16%), and central nervous system infections (13%), while the leading barriers to care were cost (58%) and difficulties with travel (53%). Compared to controls, recently deceased children came from families with significantly lower incomes (1905 Kwacha vs. 2412 Kwacha, p = 0.03) and were significantly more likely to have a history of malnutrition (16.7% vs. 1.4%, p = 0.005). Mortality was clustered in two high-population density, low-income neighborhoods in Lusaka. Systems to reduce financial barriers to care and improve access to transportation could reduce childhood mortality in Lusaka. The aforementioned neighborhoods are ideal locations for public health interventions or improved healthcare services.

Microglia and macrophages alterations in the CNS during acute SIV infection: A single-cell analysis in rhesus macaques.

Human Immunodeficiency Virus (HIV) is widely acknowledged for its profound impact on the immune system. Although HIV primarily affects peripheral CD4 T cells, its influence on the central nervous system (CNS) cannot be overlooked. Within the brain, microglia and CNS-associated macrophages (CAMs) serve as the primary targets for HIV and the simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects and establish a viral reservoir. Given the gaps in our understanding of how these cells respond in vivo to acute CNS infection, we conducted single-cell RNA sequencing (scRNA-seq) on myeloid cells from the brains of three rhesus macaques 12 days after SIV infection, along with three uninfected controls. Our analysis revealed six distinct microglial clusters including homeostatic microglia, preactivated microglia, and activated microglia expressing high levels of inflammatory and disease-related molecules. In response to acute SIV infection, the homeostatic and preactivated microglia population decreased, while the activated and disease-related microglia increased. All microglial clusters exhibited upregulation of MHC class I molecules and interferon-related genes, indicating their crucial roles in defending against SIV during the acute phase. All microglia clusters also upregulated genes linked to cellular senescence. Additionally, we identified two distinct CAM populations: CD14lowCD16hi and CD14hiCD16low CAMs. Interestingly, during acute SIV infection, the dominant CAM population changed to one with an inflammatory phenotype. Specific upregulated genes within one microglia and one macrophage cluster were associated with neurodegenerative pathways, suggesting potential links to neurocognitive disorders. This research sheds light on the intricate interactions between viral infection, innate immune responses, and the CNS, providing valuable insights for future investigations.

Optimization of the Diagnosis of Central Nervous System Infections in Vietnamese Hospitals: Results From a Retrospective Multicenter Study.

Central nervous system infections pose significant health challenges, particularly in low- and middle-income countries, because of high morbidity and mortality rates. Rapid and accurate diagnosis is essential for effective treatment to prevent adverse outcomes. Traditional culture-based diagnostics are often slow and lack specificity. This study evaluates the BioFire FilmArray Meningitis/Encephalitis (FAME) Panel against standard diagnostics in Vietnam to assess its clinical impact and suitability for local epidemiology. We conducted a prospective study involving 330 patients with suspected central nervous system infections at 4 hospitals in northern Vietnam from July 2022 to April 2023. Cerebrospinal fluid samples were analyzed using routine culture methods and FAME. We compared pathogen detection rates and assessed the potential clinical impact of FAME results on patient management. Of the 330 cerebrospinal fluid specimens, 64 (19%) were positive by either conventional diagnostics (n = 48) and/or FAME (n = 33). The agreement between FAME and conventional diagnostics was 87%. Key pathogens Mycobacterium tuberculosis (n = 7), Klebsiella pneumoniae (n = 5), Streptococcus suis (n = 5), Epstein-Barr virus (n = 3), Acinetobacter baumannii (n = 1), and Trichosporon asahii (n = 1) were not detected by FAME. Classical meningitis parameter clinical symptoms, altered glucose, protein, and pleocytosis were good predictors of FAME positivity, indicating their utility in optimizing local diagnostic algorithms. FAME complements traditional diagnostics by offering rapid and broad pathogen detection, crucial for timely and appropriate therapy. However, its effectiveness varies with local epidemiology, and it should not replace conventional methods entirely. Tailoring diagnostic panels to regional pathogen prevalence is recommended to enhance diagnostic accuracy and clinical outcomes in low- and middle-income countries.

Melatonin as a Treatment Option for Bacterial Meningitis – A Comprehensive Review

Bacterial meningitis (BM) is a global acute infectious central nervous system (CNS) illness that leaves 50% of survivors with long-term significant consequences. Acute bacterial meningitis is more common in low-resource areas than in high-resource areas. Bacterial survival and multiplication in the circulation, increased permeability of the blood brain barrier (BBB), oxidative stress, and an overactive inflammatory response in the CNS are all involved in the pathogenesis of BM. Because drug-resistant bacteria make treatment for meningitis more difficult, the vaccination has been confined to a few serotypes, and the BM morbidity rate remains high. With recent advances in neurology, there is hope for medication supplements that can successfully prevent and cure BM. Several in vivo and in vitro researches have been conducted to better understand how melatonin affects BM. Melatonin is primarily produced in the pineal gland and has the ability to cross the BBB. Melatonin and its metabolite have been found to be efficient antioxidants and anti-inflammatories, suggesting that they might be used to prevent and treat BM. Melatonin can protect the brain against bacterial meningitis through a variety of mechanisms, including immunological response, antibacterial capabilities, BBB integrity protection, free radical scavenging, anti-inflammation, signalling pathways, and gut microbiota. This paper highlights melatonin's primary neuroprotective processes and investigates prospective preventative and therapy strategies for BM nerve damage. Keywords: Bacterial Meningitis, Neuron Injury, Melatonin, Neuroprotection