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Frontiers in Pediatrics 2024Infectious encephalopathy (IE), including meningitis, infectious encephalitis, and cerebral abscess, remains prevalent and carries high mortality and morbidity in...
INTRODUCTION
Infectious encephalopathy (IE), including meningitis, infectious encephalitis, and cerebral abscess, remains prevalent and carries high mortality and morbidity in children, especially in low and middle income countries (LMIC). This study aims to describe the usual care and outcomes of pediatric IE in four LMIC hospitals in sub-Saharan Africa to support evidence-based care guideline development.
METHODS
This is a secondary analysis of the Prevalence of Acute Critical Neurological disease in children: A Global Epidemiological Assessment-Developing Countries study, a 4-week, prospective, observational study in children (1 week to 17 years) with IE presenting to referral hospitals in Ethiopia, Kenya, Rwanda, and Ghana. Data collection included diagnostic testing, interventions, and patient outcomes [e.g., mortality, Pediatric Cerebral and Overall Performance Category Scores (PCPC and POPC)].
RESULTS
Seventy-two children with IE were enrolled. Most patients were diagnosed with undifferentiated IE (78%, = 56). Specific etiologies included cerebral malaria (10%, = 7), viral encephalitis (4%, = 3), tuberculosis (4%, = 3), bacterial meningitis (3%, = 2), and cerebral abscess (1%, = 1). Fourteen patients (20%) had a head computed tomography performed. Thirty two (44%) children had a lumbar puncture but only 9 samples (28%) were sent for culture. Median time from diagnosis to antimicrobial therapy was 3 h (IQR 1-12 h). Half (51%, = 33) of inpatients received intracranial pressure (ICP)-directed treatment but none underwent ICP monitoring. Mortality was 13% ( = 9). The percentage of children with a favorable cognitive score decreased from 95% ( = 62) prior to admission to 80% ( = 52) and 77% ( = 50) at discharge for PCPC and POPC respectively.
DISCUSSION
IE led to considerable morbidity and mortality in this cohort, and evaluation and management varied across the care continuum. Resource limitations and diagnostic constraints may have affected diagnosis-directed therapy and other aspects of management. Further studies are needed to describe the epidemiology and management of IE in LMICs to inform future treatment protocols, the role of technological and human capacity building to support both basic monitoring and interventions, as well as creative new solutions to emergency and critical care in these settings.
PubMed: 38464900
DOI: 10.3389/fped.2024.1304245 -
Practical Laboratory Medicine Mar 2024The aim of this study was to demonstrate the performance and added value of rapid glucose determination in cerebrospinal fluid using a connected glucometer.
OBJECTIVES
The aim of this study was to demonstrate the performance and added value of rapid glucose determination in cerebrospinal fluid using a connected glucometer.
DESIGN AND METHODS
Intra-assay and inter-assay accuracies were calculated using residual clinical samples. Accuracies were measured by comparing the results obtained with the glucometer to those from the central laboratory on a large routine chemistry platform.
RESULTS
The intra-assay coefficients of variation were between 6.1% and 6.2% for low values (18 mg/dL) and between 5.6% and 6.8% for high values (58 mg/dL). The inter-assay coefficients of variation were between 9.4% and 16.3% for the low values (18 mg/dL) and between 5.7% and 8.7% for the high values (pool; ±75 mg/dL). The regression equation by comparison to the central laboratory was y = 4.08 + 0.82 x, with a coefficient of determination (r) of 0.95.
CONCLUSIONS
The measurement of glycorrhachia with a connected glucometer before the analysis in the central laboratory allows a rapid orientation in the deferential diagnosis of a meningitis of viral vs bacterial origin. The response time is fast (6 s) and requires only a small amount of fluid (1.2 μL), which is important in infants, especially since lumbar puncture is an integral part of the investigation of the origin of a fever in this population.
PubMed: 38463197
DOI: 10.1016/j.plabm.2024.e00384 -
Journal of the Neurological Sciences Apr 2024To investigate the short-term benefits and adverse effects of ketamine in the treatment of pediatric and adolescent super-refractory status epilepticus (SRSE), with a... (Observational Study)
Observational Study
OBJECTIVE
To investigate the short-term benefits and adverse effects of ketamine in the treatment of pediatric and adolescent super-refractory status epilepticus (SRSE), with a focus on the inflammatory etiology.
METHODS
This retrospective observational cohort study included a consecutive series of 18 pediatric to adolescent patients with SRSE admitted between 2008 and 2023 and treated with ketamine. Seizure frequency per hour before and after ketamine administration and response rate were calculated. Neurological decline, catecholamine administration, and adverse effects were also assessed. The patients were divided into inflammatory and non-inflammatory etiology groups.
RESULTS
The median age at SRSE onset was 1 year 5 months (range: 11 days-24 years), and 78% of the patients were male individuals. The median duration of treatment was 7.5 days (interquartile range: 2.8-15.5 days). Fifteen (83%) patients achieved >50% seizure reduction. The median seizure frequency before and after ketamine treatment was 5.9 and 0.9, respectively, showing a significant reduction in seizure frequency (p < 0.0001). Ten patients had inflammatory etiologies including bacterial meningitis (n = 2), viral encephalitis (n = 3), and febrile infection related epilepsy syndrome (n = 5). The inflammatory etiology group required a longer treatment duration (p = 0.0453) and showed lower seizure reduction (p = 0.0264), lower response rate (p = 0.0044), and higher neurological decline (p = 0.0003) than the non-inflammatory etiology group. Three (17%) patients experienced transient adverse events requiring intervention within 24 h of initiating ketamine administration.
CONCLUSIONS
Ketamine administration was associated with fewer serious adverse events and a reduced seizure frequency. Additionally, inflammatory conditions may weaken the efficacy of ketamine in patients with SRSE.
Topics: Humans; Child; Male; Adolescent; Infant, Newborn; Female; Ketamine; Retrospective Studies; Anticonvulsants; Status Epilepticus; Seizures; Neuromuscular Diseases; Drug-Related Side Effects and Adverse Reactions
PubMed: 38461760
DOI: 10.1016/j.jns.2024.122950 -
Translational Pediatrics Feb 2024Influenza A is the most common viral pathogen isolated from pediatric clinics during influenza seasons. Some young patients with influenza manifest rapid progression...
BACKGROUND
Influenza A is the most common viral pathogen isolated from pediatric clinics during influenza seasons. Some young patients with influenza manifest rapid progression with high fever and severe sequelae, such as pneumonia and meningitis. Therefore, early diagnosis and prompt treatment are highly important. Specific diagnostic tests currently include antigen detection, antibody detection, nucleic acid test and virus isolation. Rapid antigen testing is the most commonly adopted method in the outpatient setting, but false negative results are frequently observed, which causes delayed treatment and severe outcome. Routine blood test is the most commonly used detection for the outpatients. Incorporating specific blood cell counts into rapid antigen test may overcome some technical issues and enable accurate early diagnosis.
METHODS
We enrolled 537 children with influenza-like symptoms like fever or respiratory symptoms from pediatric outpatients and 110 children without infectious diseases for control. Routine blood tests detected by a routine analyzer and influenza A virus antigen detection were performed in the patients. Significant blood routine parameters between groups were examined by statistical tests. Parameters in routine blood test were assessed by the receiver operating characteristic curve to find the screening indicators of influenza A. Multivariate logistic regression were used to establish the optimal combinations of blood routine parameters in our screening model.
RESULTS
Two subgroups were set according to age: ≤6 years old group and >6 years old group. In each group, patients were further divided into three subgroups: the influenza A-positive-result group (A+ group) (n=259), influenza A-negative-result group (A- group) (n=277) and healthy control group (H group) (n=110). Most routine blood parameters showed significant differences among the three subgroups in each age group. Notably, lymphocyte (LYM) number, platelet (PLT) number, lymphocyte-to-monocyte ratio (LMR) and LYM multiplied by PLT (LYM*PLT) exhibited extremely significant differences. Using A- group as a reference based on the area under the curve (AUC), both age groups had a similar trend. For A- group, the optimal cutoff value of LYM*PLT was 221.6, the AUC, the sensitivity and specificity were 0.6830, 55.71% and 76.92% in the ≤6 years old group. Meanwhile, the cutoff value of LYM*PLT was 196.7, and the AUC, the sensitivity and specificity were 0.6448, 53.97% and 70.81%, respectively in the >6 years old group. Screening model based on multivariate logistic regression model revealed that LYM*PLT was the optimal parameter combinations in ≤6 years old group (AUC =0.7202), while LYM and PLT were the optimal parameter combinations in >6 years old group (AUC =0.6760).
CONCLUSIONS
Several blood routine parameters in children with influenza A demonstrate differential levels in both age subgroups. The LYM*PLT exhibits the potential screening value of influenza infection.
PubMed: 38455751
DOI: 10.21037/tp-23-435 -
Nature Mar 2024Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function. To study these 'kiss-and-run' interactions...
Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function. To study these 'kiss-and-run' interactions directly in vivo, we previously developed LIPSTIC (labelling immune partnerships by SorTagging intercellular contacts), an approach that uses enzymatic transfer of a labelled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4 T helper cells and antigen-presenting cells, however. Here we report the development of a universal version of LIPSTIC (uLIPSTIC), which can record physical interactions both among immune cells and between immune and non-immune populations irrespective of the receptors and ligands involved. We show that uLIPSTIC can be used, among other things, to monitor the priming of CD8 T cells by dendritic cells, reveal the steady-state cellular partners of regulatory T cells and identify germinal centre-resident T follicular helper cells on the basis of their ability to interact cognately with germinal centre B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalogue of the immune populations that physically interact with intestinal epithelial cells at the steady state and profile the evolution of the interactome of lymphocytic choriomeningitis virus-specific CD8 T cells in multiple organs following systemic infection. Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell-cell interactions across multiple biological systems.
Topics: CD8-Positive T-Lymphocytes; Cell Communication; Dendritic Cells; Ligands; T-Lymphocytes, Regulatory; T Follicular Helper Cells; B-Lymphocytes; Germinal Center; Single-Cell Gene Expression Analysis; Epithelial Cells; Intestinal Mucosa; Lymphocytic choriomeningitis virus; Lymphocytic Choriomeningitis; Organ Specificity
PubMed: 38448581
DOI: 10.1038/s41586-024-07134-4 -
Clinical Case Reports Mar 2024EBV infections rarely cause CNS involvement. For young adult patients with suspected CNS infection, bacterial and other common viral infections should be excluded first...
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.
PubMed: 38444918
DOI: 10.1002/ccr3.8568 -
European Journal of Clinical... May 2024Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance...
PURPOSE
Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS).
METHODS
A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines.
RESULTS
Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections.
CONCLUSION
This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings.
Topics: Humans; Child, Preschool; Prospective Studies; Female; Male; Child; Viruses; Infant; Metagenomics; Encephalitis; Cerebrospinal Fluid; Meningitis, Viral; Adolescent; High-Throughput Nucleotide Sequencing; Spain; Meningitis; Encephalitis, Viral
PubMed: 38438704
DOI: 10.1007/s10096-024-04795-x -
Internal Medicine (Tokyo, Japan) May 2024Objective The changes in the prevalence of acute meningitis during the coronavirus disease 2019 (COVID-19) pandemic remain unclear. This study aimed to compare the...
Objective The changes in the prevalence of acute meningitis during the coronavirus disease 2019 (COVID-19) pandemic remain unclear. This study aimed to compare the prevalence of acute meningitis before and during the COVID-19 pandemic in Japan. Methods We retrospectively reviewed the Japanese nationwide administrative medical payment system database, Diagnosis Procedure Combination (DPC), from 2016 to 2022. A total of 547 hospitals consistently and seamlessly offered DPC data during this period. The study period was divided into the following three periods: April 2016 to March 2018 (fiscal years 2016-2017), April 2018-March 2020 (2018-2019), and April 2020-March 2022 (2020-2021). Results Among the 28,161,806 patients hospitalized during the study period, 28,399 were hospitalized for acute meningitis: 16,678 for viral/aseptic type, 6,189 for bacterial type, 655 for fungal type, 429 for tuberculous, 2,310 for carcinomatous type, and 2,138 for other or unknown types of meningitis. A significant decrease during the pandemic was confirmed in viral (n=7,032, n=5,775, and n=3,871 in each period; p<0.0001) and bacterial meningitis (n=2,291, n=2,239, and n=1,659; p<0.0001) cases. Meanwhile, no decrease was observed in fungal meningitis (n=212, n=246, and n=197; p=0.056) or carcinomatous meningitis (n=781, n=795, and n=734; p=0.27). The decrease in the number of tuberculous meningitis cases was equivocal (n=166, n=146, and n=117; p=0.014). The decrease during the pandemic was more remarkable in younger populations aged <50 years than in older populations, both for viral and bacterial meningitis. Conclusion The number of hospitalized cases of acute meningitis clearly decreased during the COVID-19 pandemic, especially for viral and bacterial meningitis in younger populations aged <50 years.
Topics: Humans; COVID-19; Japan; Middle Aged; Retrospective Studies; Aged; Male; Female; Hospitalization; Adult; Young Adult; Adolescent; Aged, 80 and over; Prevalence; Child; Child, Preschool; Acute Disease; Infant; Meningitis; SARS-CoV-2; Meningitis, Viral; Pandemics; Infant, Newborn
PubMed: 38432966
DOI: 10.2169/internalmedicine.3022-23