Distinct Replication Kinetics, Cytopathogenicity, and Immune Gene Regulation in Human Microglia Cells Infected with Asian and African Lineages of Zika Virus.

Zika virus (ZIKV), a mosquito-borne flavivirus, is a significant global health concern due to its association with neurodevelopmental disorders such as congenital Zika syndrome (CZS). This study aimed to compare the replication kinetics, viral persistence, cytopathogenic effects, and immune gene expression in human microglia cells (CHME-3) infected with an Asian lineage ZIKV (PRVABC59, referred to as ZIKV-PRV) and an African lineage ZIKV (IBH30656, referred to as ZIKV-IBH). We found that ZIKV-PRV replicated more efficiently and persisted longer while inducing lower levels of cell death and inflammatory gene activation compared with ZIKV-IBH. These findings suggest that the enhanced replication and persistence of ZIKV-PRV, along with its ability to evade innate immune responses, may underlie its increased neuropathogenic potential, especially in the context of CZS. In contrast, ZIKV-IBH, with its stronger immune gene activation and higher cytopathogenicity, may lead to more acute infections with faster viral clearance, thereby reducing the likelihood of chronic central nervous system (CNS) infection. This study provides crucial insights into the molecular and cellular mechanisms driving the differential pathogenicity of ZIKV lineages and highlights the need for further research to pinpoint the viral factors responsible for these distinct clinical outcomes.

Risk factors and chlorhexidine dressings in external ventricular drainage: a retrospective analysis on infection rates.

This retrospective study endeavors to scrutinize risk factors associated with infections resulting from external ventricular drainage (EVD) and to assess the effectiveness of chlorhexidine dressing in mitigating infection rates. Conducted from January 2018 to July 2023, this single-center study encompassed 108 EVD patients. Comprehensive data on demographics, comorbidities, surgical procedures, and the utilization of chlorhexidine dressing were meticulously compiled. The primary endpoint was the incidence of EVD-associated infections based on CDC criteria. Infection rates attributable to EVD were 24.32% without and 20.59% with chlorhexidine dressing. Notably, diabetes mellitus emerged as the solitary significant infection risk factor (p < 0.01). Although the application of chlorhexidine dressing suggested a propensity for diminishing infection rates, statistical significance remained elusive. No notable disparities were discerned in variables such as catheter type, procedural location, and underlying diseases. Diabetes mellitus has been identified as a significant risk factor for EVD-associated infections. While the utilization of chlorhexidine dressing exhibited a potential reduction in infection rates, the lack of statistical significance underscores the imperative for further research, encompassing more expansive randomized trials, to comprehensively evaluate the safety and efficacy of chlorhexidine dressings in preventing EVD-associated infections.

The Impact of Infectious Diseases on Psychiatric Disorders: A Systematic Review.

The complex connection between some infectious illnesses and some psychiatric disorders is an important area of study, with infections known to cause a diverse range of psychiatric symptoms. This association poses significant challenges for physicians in differentiating between mental illnesses induced by infections and those stemming from underlying psychiatric conditions. This study systematically synthesizes literature from various databases that explain the relationship between certain infectious diseases and specific psychiatric disorders. The systematic review explores mechanisms such as neuroinflammation, direct central nervous system (CNS) infection, and the interaction between the immune system and psychiatric conditions. The study examines various infectious pathogens, including viruses, bacteria, parasites, prion diseases, and fungi. An analysis of these findings is presented in the study's discussion section, along with a review of therapeutic methods such as drug use and psychological treatment. The review emphasizes the need for multidisciplinary teamwork and thorough clinical examinations in managing psychiatric symptoms caused by infections. It also highlights the significant role of public health measures in mitigating the impact of psychiatric diseases related to infectious illnesses. The study finds that current therapeutic methods include pharmacological and psychological treatments, which can effectively manage these conditions. The study has concluded that psychiatric manifestations are prevalent across various infectious diseases, including those caused by viruses, bacteria, parasites, and fungi. Key mechanisms identified include neuroinflammation, direct infection of the CNS, and the immuno-psychiatric interface, all of which contribute to the development of psychiatric symptoms. The future of managing these complex conditions lies in a comprehensive approach that combines clinical, therapeutic, and public health strategies.

Paroxysmal Sympathetic Hyperactivity in Childhood Tuberculous Meningitis: A New Association.

BACKGROUND: We sought to estimate the prevalence and clinical characteristics of paroxysmal sympathetic hyperactivity (PSH) in childhood tuberculous meningitis. METHODS: Hospital records of children (6 months to 14 years) with tuberculous meningitis were retrospectively analyzed from September 2019 through January 2022. In September 2019, the first case of paroxysmal sympathetic hyperactivity in tuberculous meningitis was identified in our division. Since then, all admitted children with tuberculous meningitis have been screened for paroxysmal sympathetic hyperactivity using the Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM). Paroxysmal sympathetic hyperactivity is suspected when any of the following are present: recurrence of fever after initial defervescence, episodic posturing, dystonia, or unexplained tachycardia. Outcome at 3 months was prospectively scored according to the Pediatric Cerebral Performance Category score. RESULTS: Forty-one hospital records of children with tuberculous meningitis were analyzed, and 6 of them had paroxysmal sympathetic hyperactivity (probable paroxysmal sympathetic hyperactivity, 5/6; possible paroxysmal sympathetic hyperactivity, 1/6). Paroxysmal sympathetic hyperactivity appeared after a mean duration of 17 weeks (range: 12-25 weeks) from the diagnosis of tuberculous meningitis in 4 of 6 children and at 4 weeks in 2 of 6 children. Children with tuberculous meningitis who developed paroxysmal sympathetic hyperactivity were younger (median age: 5 years) compared with the nonparoxysmal sympathetic hyperactivity tuberculous meningitis cohort (median age: 10 years). A high proportion of children who developed paroxysmal sympathetic hyperactivity had hydrocephalus at presentation (5 of 6 [83.3%] vs 12 of 35 [34.3%], P = .035). Hospital stay was significantly prolonged in children with probable paroxysmal sympathetic hyperactivity (mean: 71.2 ± 26.8 days) compared with tuberculous meningitis without paroxysmal sympathetic hyperactivity (mean: 20.8 ± 11.6 days; P < .0001). CONCLUSION: Paroxysmal sympathetic hyperactivity is a late complication of tuberculous meningitis observed in 14.6% cases and should be anticipated in children with reappearance of fever or neurologic worsening without any apparent cause.

Toscana virus (TOSV) meningitis with atypical characteristics: Report of two cases.

Toscana virus (TOSV) is an emerging cause of central nervous system (CNS) infections, especially in endemic countries during summer. Cerebrospinal fluid (CSF) is usually clear, with < 500 leukocytes/mm3, normal glucose (> 60 % serum glucose) and normal (< 45 mg/dL) to slightly increased protein levels. Here we present two cases of TOSV meningitis with misleading CSF characteristics observed at Santa Maria Annunziata Hospital (Bagno a Ripoli, Florence, Italy). Case 1 presented with signs and symptoms of meningitis. CSF was opalescent on macroscopic examination, with 1192 cells/mm3, hypoglycorrhachia (30 % serum glucose) and hyperproteinorachia (228.0 mg/dL). TOSV meningitis was confirmed with serology. Case 2 presented with headache, vomiting and mild neck stiffness. CSF was slightly turbid, with 1092 cells/mm3, normal glucose (61 % serum glucose) and slightly increased protein (77.0 mg/dL) levels. TOSV meningitis was confirmed with serology and molecular test on CSF. We performed a literature review including cases of TOSV neuroinvasive infections in which CSF characteristics were reported. Pleocytosis > 500 cells/mm3 was reported in 12/62 (19.4 %) patients, hypoglycorrhachia in 3/62 (4.8 %) patients, mild hyperproteinorachia (45 - 75 mg/dL) in 7/62 (11.3 %) patients and severe hyperproteinorachia (> 75 mg/dL) in 40/62 (64.5 %) patients. TOSV should be considered in the differential diagnosis of CNS infections in endemic areas during the warm season even when CSF examination shows atypical results.

Ceftazidime-Avibactam for the Treatment of Central Nervous System Infection Caused by Pan Drug-Resistant Carbapenem-Resistant Klebsiella Pneumoniae: A Case Report.

Background: Central Nervous System (CNS) infections caused by Carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a major clinical challenge and are associated with high mortality rates. Polymyxin is used as a salvage treatment for CRKP CNS infection; however, heteroresistance to polymyxin may impact clinical outcomes. In this study, we report a rare case of polymyxin-resistant Klebsiella intracranial infection, which was successfully treated with intravenous and intraventricular antibiotic injections. Case Presentation: A 46-year-old woman with a 1-day history of post-traumatic disturbance of consciousness and cerebrospinal fluid (CSF) rhinorrhea was referred to our hospital. She underwent external ventricular drainage and decompressive craniectomy, and had a persistent fever. A CSF test confirmed intracranial infection. The minimum inhibitory concentration of polymyxin in this patient was 16 µg/mL. She was diagnosed with polymyxin-resistant pan drug-resistant (PDR) Klebsiella pneumoniae (PDR-Kp) intracranial infection. We successfully treated the infection using intravenous ceftazidime/avibactam (CAZ/AVI) and polymyxin B, combined with an intraventricular injection of polymyxin B according to the CSF microbiological culture results. Conclusion: CAZ/AVI combined with polymyxin B may be an effective salvage treatment for CNS infections caused by polymyxin-resistant PDR-KP.

Changes in optic nerve sheath diameter and its correlation with degree of consciousness, pupil diameter, and light reflex in children with central nervous system infection after osmotherapy.

Background: High intracranial pressure (ICP) is one of the most common complications of central nervous system (CNS) infection. Failure to control high intracranial pressure results in brain herniation and death. One of the treatments for high ICP involves the administration of osmotherapy in the form of 3% NaCl or 20% mannitol with observation during administration. Observation of ICP during administration of osmotherapy is possible through measurement of optic nerve sheath diameter (ONSD), which could be correlated with degree of consciousness, pupil diameter, and light reflex. Previous studies have not correlated ONSD with degree of consciousness, pupil diameter, and light reflex during the administration of osmotherapy. Purpose: To provide insights of incorporating ONSD measurement as a form of non-invasive bedside method for ICP monitoring by correlating it with degree of consciousness, pupil diameter, and light reflex at several time points. Methods: This study is a prospective cohort study, performed at Dr. Hasan Sadikin General Central Hospital Bandung, Cibabat General Regional Hospital, and General Regional Hospital Bandung Kiwari on children aged 2-18 years with decreased consciousness and CNS infection, from June 2023. Inter-rater reliability was performed with a correlation coefficient of 0.90. Measurement of ONSD, degree of consciousness, pupil diameter, and light reflex simultaneously up to 48 h after initiation of osmotherapy to 30 patients. Correlational analyses were performed using Spearman's rank. Results: Observation for 48 h after administration of osmotherapy showed changes in ONSD. A significant positive correlation was found between ONSD and degree of consciousness (r = 0.621 for the right eye and r = 0.602 for the left eye, p < 0.001). A significant positive correlation was found between ONSD and light reflex (r = 0.801 for the right eye and r = 0.812 for the left eye, p < 0.001). No significant correlation was found with changes of pupil diameter (r = -0.136 for the right eye and r = -0.141 for the left eye, p > 0.05). Conclusion: A significant correlation was found between ONSD and degree of consciousness and light reflex in children aged 2-18 years with CNS infection during administration of osmotherapy.

Persistent Listeria monocytogenes Cerebritis Mimicking Cerebral Metastases Due to Melanoma.

Listeria cerebritis is a rare yet serious central nervous system infection, which can present with leptomeningeal enhancement, abscess, and seizures. An adult patient with a history of metastatic melanoma presented with left-sided weakness, later identified as postictal Todd's paralysis due to focal motor seizures. Further diagnostic workup revealed a leptomeningeal abscess in the setting of listeria cerebritis. The patient's condition improved after treatment with a prolonged course of ampicillin, gentamicin, and linezolid over eight weeks. Leptomeningeal disease in patients with cancer history is often thought to be metastatic disease but infections, such as listeria, should be considered even if cerebrospinal fluid is bland. Treatment of listeria may need to be prolonged in patients who are immunocompromised.

Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India.

Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at the National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM), and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n = 8) and A. levis (n = 1), from brain abscess (n = 4), respiratory tract (n = 3), and corneal scraping (n = 2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the internal transcribed spacer ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed the lowest minimum inhibitory concentrations (MICs) for triazoles and the highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin, and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.

We describe clinical, phenotypic, and genotypic characteristics of Acrophialophora species. This species causes mild infection to fatal infection in immunosuppressed individuals. Triazoles are effective in treating such infections.

Contribution of CNS and extra-CNS infections to neurodegeneration: a narrative review.

Central nervous system infections have been suggested as a possible cause for neurodegenerative diseases, particularly sporadic cases. They trigger neuroinflammation which is considered integrally involved in neurodegenerative processes. In this review, we will look at data linking a variety of viral, bacterial, fungal, and protozoan infections to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis and unspecified dementia. This narrative review aims to bring together a broad range of data currently supporting the involvement of central nervous system infections in the development of neurodegenerative diseases. The idea that no single pathogen or pathogen group is responsible for neurodegenerative diseases will be discussed. Instead, we suggest that a wide range of susceptibility factors may make individuals differentially vulnerable to different infectious pathogens and subsequent pathologies.

Development and Validation of a Predictive Model for Postoperative Intracranial Infections in Neurosurgery with Risk Factor Analysis.

BACKGROUND: Currently, the diagnosis of postneurosurgical intracranial infection is mainly dependent on cerebrospinal fluid (CSF) bacterial culture, which has the disadvantages of being time-consuming, having a low detection rate, and being easily affected by other factors. These disadvantages bring some difficulties to early diagnosis. Therefore, it is very important to construct a nomogram model to predict the risk of infection and provide a basis for early diagnosis and treatment. METHODS: This retrospective study analyzed postneurosurgical patient data from the Fourth Affiliated Hospital of Harbin Medical University between January 2019 and September 2023. The patients were randomly assigned in an 8:2 ratio into the training cohort and the internal validation cohort. In the training cohort, initial screening of relevant indices was conducted via univariate analysis. Subsequently, the least absolute shrinkage and selection operator logistic regression identified significant potential risk factors for inclusion in the nomogram model. The model's discriminative ability was assessed using the area under the receiver operating characteristic curve, and its calibration was evaluated through calibration plots. The clinical utility of the model was determined using decision curve analysis and further validated by the internal validation cohort. RESULTS: Multivariate logistic regression analysis of the training cohort identified 7 independent risk factors for postoperative intracranial infection: duration of postoperative external drainage (odds ratio [OR] 1.19, P = 0.005), continued fever (OR 2.11, P = 0.036), CSF turbidity (OR 2.73, P = 0.014), CSF pressure (OR 1.01, P = 0.018), CSF total protein level (OR 1.26, P = 0.026), CSF glucose concentration (OR 0.74, P = 0.029), and postoperative serum albumin level (OR 0.84, P < 0.001). Using these variables to construct the final model. The area under the receiver operating characteristic curve value of the model was 0.868 in the training cohort and 0.900 in the internal validation cohort. Calibration and the decision curve analysis indicated high accuracy and clinical benefit of the nomogram, findings that were corroborated in the validation cohort. CONCLUSIONS: This study successfully developed a novel nomogram for predicting postoperative intracranial infection, demonstrating excellent predictive performance. It offers a pragmatic tool for the early diagnosis of intracranial infection.

Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity.

Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.

TAK-3 Inhibits Lipopolysaccharide-Induced Neuroinflammation in Traumatic Brain Injury Rats Through the TLR-4/NF-κB Pathway.

Purpose: The activation of the inflammatory response is regarded as a pivotal factor in the pathogenesis of TBI. Central nervous system infection often leads to the exacerbation of neuroinflammation following TBI, primarily caused by Gram-negative bacteria. This study aims to elucidate the effects of the novel anti-inflammatory drug TAK-3 on LPS-induced neuroinflammation in TBI rats. Methods: In conjunction with the rat controlled cortical impact model, we administered local injections of Lipopolysaccharide to the impact site. Subsequently, interventions were implemented through intraperitoneal injections of TAK-3 and NF-κB activitor2 to modulate the TLR4/NF-κB axis The impact of LPS on neurological function was assessed using mNSS, open field test, and brain water content measurement. Inflammatory markers, including TNF-α, IL-1ß, IL-6 and IL-10 were assessed to evaluate the condition of neuritis by Elisa. The activation of the TLR-4/NF-κB signaling pathway was detected by immunofluorescence staining and Western blot to assess the anti-inflammatory effects of TAK-3. Results: The administration of LPS exacerbated neurological damage in rats with TBI, as evidenced by a reduction in motor activity and an increase in anxiety-like behavior. Furthermore, LPS induced disruption of the blood-brain barrier integrity and facilitated the development of brain edema. The activation of microglia and astrocytes by LPS at the cellular and molecular levels has been demonstrated to induce a significant upregulation of neuroinflammatory factors. The injection of TAK-3 attenuated the neuroinflammatory response induced by LPS. Conclusion: The present study highlights the exacerbating effects of LPS on neuroinflammation in TBI through activation of the TLR-4/NF-κB signaling pathway. TAK-3 can modulate the activity of this signaling axis, thereby attenuating neuroinflammation and ultimately reducing brain tissue damage.

A Study of the Etiology, Clinical Profile, and Diagnosis of Various Types of Central Nervous System Infections in a Tertiary Care Center.

Introduction Infections affecting the central nervous system (CNS) can stem from various sources, including bacteria, viruses, and fungi, manifesting as conditions like meningitis, encephalitis, meningoencephalitis, and brain abscesses. Despite significant advancements in diagnosis and treatment, these infections continue to pose substantial risks to life. Several factors contribute to the causes of CNS infections. Demographic and geographic elements, the health status of individuals, their immune system's strength, the availability of diagnostic tools, and local prevention initiatives, all play pivotal roles. Consequently, the necessity of comprehensive local epidemiological data becomes undeniable as it guides the need for further studies and research. Understanding these factors is crucial for enhancing preventive measures and optimizing treatment strategies in tackling CNS infections. Aims and objectives This research aims to study the etiology and clinical features of different CNS infections among hospitalized patients and to diagnose cases of CNS infections based on laboratory and radiological investigations. Material and methods One hundred adults, seeking treatment for neurological impairments at a specialized tertiary care center in Gujarat, India, volunteered for this cross-sectional observational research. The study investigated the etiology, clinical profiles, and diagnoses of different CNS infections. It delved into the prevalence of these infections across age and sex categories while also observing mortality rates. Results In our research, we observed that bacterial causes were the most prevalent among CNS infections. Tubercular meningitis accounted for 36%, tuberculoma 14%, and pyogenic bacterial infections 23%. Following this, fungal infections emerged as the second most frequent, with mucormycosis at 9% and cryptococcus at 1%. Other less common CNS infections included viral encephalitis (4%), neurocysticercosis (3%), and brain abscess (1%). Middle-aged individuals between 41 and 60 years were most commonly affected (43%), followed by those aged 21-40 years (31%). Males accounted for a higher percentage of cases at 58%. Clinical symptoms revealed fever as the predominant feature (80%), with headaches following closely at 67%. Acute presentations were prevalent, representing 83% of cases, while neck stiffness was noted in 62% of patients. Most patients exhibited normal hemoglobin levels (96%) and a majority had a normal total leukocyte count (79%). Notably, 31% of the studied patients were identified as People Living With HIV (PLHIV). Out of 100 patients, 79 survived with appropriate treatment, resulting in a mortality of 21%. Conclusion The study identified various CNS infections, including bacterial (acute pyogenic meningitis, tubercular meningitis, tuberculoma, brain abscesses, and neurosyphilis), viral (viral meningitis and encephalitis), fungal (cryptococcal meningitis and CNS mucormycosis), and parasitic infections (neurocysticercosis and CNS toxoplasmosis). Tuberculous meningitis emerged as the most prevalent, followed by pyogenic meningitis. Clinical symptoms predominantly featured fever, headache, and altered sensorium, with less common occurrences of seizures, vomiting, weakness, and speech disturbances. Elevated CSF proteins and total leukocyte count were common findings in CSF analysis while consistent radiological observations included hypodensities in brain tissue and leptomeningeal enhancement.

EBV-associated CNS infection in an immunocompetent adult: A case report and literature review.

EBV infections rarely cause CNS involvement. For young adult patients with suspected CNS infection, bacterial and other common viral infections should be excluded first and treated empirically until proven otherwise. Challenges in diagnosing EBV-associated CNS infection, emphasizing the role of CSF PCR in confirming the diagnosis.

Microbiomes detected by cerebrospinal fluid metagenomic next-generation sequencing among patients with and without HIV with suspected central nervous system infection.

BACKGROUND: Opportunistic infections in the central nervous system (CNS) can be a serious threat to people living with HIV. Early aetiological diagnosis and targeted treatment are crucial but difficult. Metagenomic next-generation sequencing (mNGS) has significant advantages over traditional detection methods. However, differences in the cerebrospinal fluid (CSF) microbiome profiles of patients living with and without HIV with suspected CNS infections using mNGS and conventional testing methods have not yet been adequately evaluated. METHODS: We conducted a retrospective cohort study in the first hospital of Changsha between January 2019 and June 2022 to investigate the microbiomes detected using mNGS of the CSF of patients living with and without HIV with suspected CNS infections. The pathogens causing CNS infections were concurrently identified using both mNGS and traditional detection methods. The spectrum of pathogens identified was compared between the two groups. RESULTS: Overall, 173 patients (140 with and 33 without HIV) with suspected CNS infection were enrolled in our study. In total, 106 (75.7%) patients with and 16 (48.5%) patients without HIV tested positive with mNGS (p = 0.002). Among the enrolled patients, 71 (50.7%) with HIV and five (15.2%) without HIV tested positive for two or more pathogens (p < 0.001). Patients with HIV had significantly higher proportions of fungus (20.7% vs. 3.0%, p = 0.016) and DNA virus (59.3% vs. 21.2%, p < 0.001) than those without HIV. Epstein-Barr virus (33.6%) was the most commonly identified potential pathogen in the CSF of patients living with HIV using mNGS, followed by cytomegalovirus (20.7%) and torque teno virus (13.8%). The top three causative pathogens identified in patients without HIV were Streptococcus (18.2%), Epstein-Barr virus (12.1%), and Mycobacterium tuberculosis (9.1%). In total, 113 patients living with HIV were diagnosed as having CNS infections. The rate of pathogen detection in people living with HIV with a CNS infection was significantly higher with mNGS than with conventional methods (93.8% vs. 15.0%, p < 0.001). CONCLUSION: CSF microbiome profiles differ between patients living with and without HIV with suspected CNS infection. mNGS is a powerful tool for the diagnosis of CNS infection among people living with HIV, especially in those with mixed infections.

Computed tomography and magnetic resonance imaging findings in central nervous system listeriosis.

PURPOSE: To describe the imaging findings and determine the incidence of a characteristic worm-like pattern along the white matter tracts in neurolisteriosis on CT/MRI. METHODS: An IRB-approved retrospective study in 21 consecutive neurolisteriosis cases during January 2002-July 2020. At least one of the following is required: (1) Positive Listeria monocytogenes (LM) in blood with clinical signs of meningeal irritation and/or abnormal CSF profile, (2) positive LM in blood with signs of encephalitis, (3) positive LM in CSF, (4) positive LM from brain biopsy/aspiration. Six cases were excluded due to the lack of contrast-enhanced images, leaving a total of 15 cases for analysis (mean age 53.5 years ± 18.8 SD). The imaging studies were independently reviewed by two blinded readers. Demographic data, imaging findings, and incidence of the worm-like pattern were reported. The Cohen's kappa was used to calculate interrater reproducibility. RESULTS: Of the 12 patients with relevant imaging findings, nine cases (75%) had parenchymal lesions (eight cases in supratentorial compartment and one case in infratentorial compartment), four cases (33.3%) had leptomeningeal enhancement and two cases (16.7%) had hydrocephalus. Brain abscesses were found in eight cases and nodules evocative of abscess in one case. Restricted diffusion in the central area and hemosiderin deposition were observed in all cases. The involvement of white matter tract in a worm-like pattern was demonstrated in eight of nine patients with parenchymal lesions (88.9%). CONCLUSION: Abnormal findings in brain CT/MRI images are common in neurolisteriosis. The incidence of worm-like spread along the white matter tracts is high and may help diagnose suspicious patients.

Diagnostic accuracy of inflammatory markers in adults with suspected central nervous system infections.

OBJECTIVES: We aimed to determine diagnostic accuracy of inflammatory markers in plasma and cerebrospinal fluid (CSF) for the diagnosis of central nervous system (CNS) infections and specifically bacterial meningitis. METHODS: We analyzed 12 cytokines, chemokines, and acute phase reactants in CSF and plasma of 738 patients with suspected neurological infection included in a multicenter prospective cohort. We determined diagnostic accuracy for predicting any CNS infection and bacterial meningitis. RESULTS: We included 738 episodes between 2017 and 2022, split into a derivation (n = 450) and validation cohort (n = 288). Of these patients, 224 (30%) were diagnosed with CNS infection, of which 81 (11%) with bacterial meningitis, 107 (14%) with viral meningitis or encephalitis, and 35 patients (5%) with another CNS infection. Diagnostic accuracy of CRP, IL-6, and Il-1ß in CSF was high, especially for diagnosing bacterial meningitis. Combining these biomarkers in a multivariable model increased accuracy and provided excellent discrimination between bacterial meningitis and all other disorders (AUC = 0.99), outperforming all individual biomarkers as well as CSF leukocytes (AUC = 0.97). When applied to the population of patients with a CSF leukocyte count of 5-1000 cells/mm3, accuracy of the model also provided a high diagnostic accuracy (AUC model = 0.97 vs. AUC CSF leukocytes = 0.80) with 100% sensitivity and 92% specificity. These results remained robust in a temporal validation cohort. CONCLUSIONS: Inflammatory biomarkers in CSF are able to differentiate CNS infections and especially bacterial meningitis from other disorders. When these biomarkers are combined, their diagnostic accuracy exceeds that of CSF leukocytes alone and as such these markers have added value to current clinical practice.

Pro-inflammatory cerebrospinal fluid profile of neonates with intraventricular hemorrhage: clinical relevance and contrast with CNS infection.

BACKGROUND: Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters. METHODS: Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH1/2), 13 IVH grade 3/4 (IVH3/4), 15 PHH, 20 culture-confirmed bacterial meningitis (BM), and 27 viral meningitis (VM) infants at 36.5 ± 4 weeks estimated gestational age. RESULTS: PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH1/2, BM, and VM infants. No differences in white blood cell (WBC) count were found between IVH3/4, PHH, BM, and VM infants. CSF neutrophil counts increased (p ≤ 0.03) for all groups compared to controls except IVH1/2. CSF protein levels were higher (p ≤ 0.02) and CSF glucose levels were lower (p ≤ 0.003) for PHH infants compared to all other groups. In peripheral blood, PHH infants had higher (p ≤ 0.001) WBC counts and lower (p ≤ 0.03) hemoglobin and hematocrit than all groups except for IVH3/4. CONCLUSIONS: Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis.

Clinical presentation, management, and outcome of suspected central nervous system infections in Indonesia: a prospective cohort study.

BACKGROUND: Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV. METHODS: We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized. We recorded initial and final diagnoses, treatments, and outcomes during 6 months of follow-up. RESULTS: Of 1051 patients screened, 793 were diagnosed with a CNS infection. Patients (median age 33 years, 62% male, 38% HIV-infected) presented a median of 14 days (IQR 7-30) after symptom onset, often with altered consciousness (63%), motor deficits (73%), and seizures (21%). Among HIV-uninfected patients, CNS tuberculosis (TB) was most common (60%), while viral (8%) and bacterial (4%) disease were uncommon. Among HIV-infected patients, cerebral toxoplasmosis (41%) was most common, followed by CNS TB (19%), neurosyphilis (15%), and cryptococcal meningitis (10%). A microbiologically confirmed diagnosis was achieved in 25% of cases, and initial diagnoses were revised in 46% of cases. In-hospital mortality was 30%, and at six months, 45% of patients had died, and 12% suffered from severe disability. Six-month mortality was associated with older age, HIV, and severe clinical, radiological and CSF markers at presentation. CONCLUSION: CNS infections in Indonesia are characterized by late presentation, severe disease, frequent HIV coinfection, low microbiological confirmation and high mortality. These findings highlight the need for earlier disease recognition, faster and more accurate diagnosis, and optimized treatment, coupled with wider efforts to improve the uptake of HIV services.