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Journal of Immunology (Baltimore, Md. :... May 2024Increased receptor binding affinity may allow viruses to escape from Ab-mediated inhibition. However, how high-affinity receptor binding affects innate immune escape and...
Increased receptor binding affinity may allow viruses to escape from Ab-mediated inhibition. However, how high-affinity receptor binding affects innate immune escape and T cell function is poorly understood. In this study, we used the lymphocytic choriomeningitis virus (LCMV) murine infection model system to create a mutated LCMV exhibiting higher affinity for the entry receptor α-dystroglycan (LCMV-GPH155Y). We show that high-affinity receptor binding results in increased viral entry, which is associated with type I IFN (IFN-I) resistance, whereas initial innate immune activation was not impaired during high-affinity virus infection in mice. Consequently, IFN-I resistance led to defective antiviral T cell immunity, reduced type II IFN, and prolonged viral replication in this murine model system. Taken together, we show that high-affinity receptor binding of viruses can trigger innate affinity escape including resistance to IFN-I resulting in prolonged viral replication.
Topics: Mice; Animals; Virus Internalization; Mice, Knockout; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Virus Replication; Mice, Inbred C57BL; Immunity, Innate
PubMed: 38497668
DOI: 10.4049/jimmunol.2300637 -
Cureus Feb 2024Introduction Infections affecting the central nervous system (CNS) can stem from various sources, including bacteria, viruses, and fungi, manifesting as conditions like...
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.
PubMed: 38496139
DOI: 10.7759/cureus.54250 -
The Israel Medical Association Journal... Mar 2024Hypothermia, as a sign of serious bacterial infection (SBI) in children and infants older than 90 days is poorly characterized, especially in the post-pneumococcal...
BACKGROUND
Hypothermia, as a sign of serious bacterial infection (SBI) in children and infants older than 90 days is poorly characterized, especially in the post-pneumococcal vaccine era.
OBJECTIVES
To assess the prevalence of SBI in children and infants presenting to the pediatric emergency department (PED) with reported or documented hypothermia.
METHODS
Retrospective data analysis was conducted of all well-appearing children aged 0-16 years who presented with a diagnosis of hypothermia at two tertiary PEDs from 2010 to 2019.
RESULTS
The study comprised 99 children, 15 (15.2%) age 0-3 months, 71 (71.7%) 3-36 months, and 13 (13.1%) > 36 months. The youngest age group had increased length of stay in the hospital (P < 0.001) and increased rates of pediatric intensive care unit admissions (P < 0.001). Empirical antibiotic coverage was initiated in 80% of the children in the 0-3 months group, 21.1% in the 3-36 months group, and 15.4% in > 36 months (P < 0.001). Only one case of SBI was recorded and no bacteremia or meningitis. Hypothermia of unknown origin was the most common diagnosis in all age groups (34%, 42%, 46%), respectively, followed by bronchiolitis (26%) and hypoglycemia (13.3%) for 0-3 month-old children, unspecified viral infection (20%) and otitis media (7%) for 3-36-month old, and unspecified viral infection (23%) and alcohol intoxication (15.2%) in > 36 months.
CONCLUSIONS
There is a low incidence of SBI in well-appearing children presenting to the PED with hypothermia and a benign course and outcome in those older than 3 months.
Topics: Child; Child, Preschool; Humans; Infant; Bacterial Infections; Emergency Service, Hospital; Hypothermia; Retrospective Studies; Urinary Tract Infections; Virus Diseases; Infant, Newborn; Adolescent
PubMed: 38493326
DOI: No ID Found -
Biomedical Journal Mar 2024Enterovirus A71 (EV-A71) infections pose a significant public health concern in the Asia-Pacific region. EV-A71 is primarily responsible for causing hand, foot, and... (Review)
Review
Enterovirus A71 (EV-A71) infections pose a significant public health concern in the Asia-Pacific region. EV-A71 is primarily responsible for causing hand, foot, and mouth disease (HFMD) in children. However, this virus can also lead to severe and potentially fatal neurological consequences in affected individuals. This review aims to provide a comprehensive understanding of the molecular virology, epidemiology, and recombination events associated with EV-A71. The literature extensively covers the clinical manifestations and neurological symptoms that accompany EV-A71 infections. One of the complications explored in this review is brainstem encephalitis, which can arise as a result of EV-A71 infections. Brainstem encephalitis refers to inflammation of the brainstem, a critical region responsible for various bodily functions. The review examines the underlying mechanisms, diagnostic criteria, treatment options, and prognosis for central nervous system infections involving EV-A71. Neurological complications associated with EV-A71 infections are diverse and can have severe consequences. These complications may include aseptic meningitis, acute flaccid paralysis, and acute transverse myelitis. The review delves into the pathophysiology of these complications, shedding light on the molecular mechanisms through which EV-A71 affects the central nervous system. Accurate diagnosis of EV-A71 infections is crucial for appropriate management and treatment. Treatment options for EV-A71 infections primarily focus on supportive care, as there are currently no specific antiviral drugs available for this virus. The review highlights the importance of managing symptoms, such as fever, dehydration, and pain relief, to alleviate the burden on affected individuals. Prognosis for individuals with central nervous system (CNS) infections involving EV-A71 can vary depending on the severity of the complications. The review provides insights into the long-term outcomes and potential neurological sequelae associated with EV-A71 infections. In conclusion, EV-A71 infections have emerged as a major public health concern in the Asia-Pacific region. This review aims to enhance our understanding of the molecular virology, epidemiology, and neurological complications associated with EV-A71. By examining the underlying mechanisms, diagnostic criteria, treatment options, and prognosis, this review contributes to the development of effective strategies for the prevention, diagnosis, and management of EV-A71 infections. The paper presents a comprehensive analysis of worldwide data pertaining to outbreaks of EV-A71 and HFMD. The subsequent discourse delves into the advancement and strategic formulation pertaining to the creation of vaccines targeting EV-A71. In summary, this study provides a comprehensive examination of the potential obstacles and considerations involved in the management and treatment of EV-A71 infections. Additionally, it proposes suggestions for future research and development endeavors with the objective of formulating efficacious treatment approaches for this viral infection.
PubMed: 38492637
DOI: 10.1016/j.bj.2024.100715 -
European Journal of Pediatrics Jun 2024Parechovirus (HpEV) and Enterovirus (EV) infections in children mostly have a mild course but are particularly fearsome in newborns in whom they may cause aseptic...
Parechovirus (HpEV) and Enterovirus (EV) infections in children mostly have a mild course but are particularly fearsome in newborns in whom they may cause aseptic meningitis, encephalitis, and myocarditis. Our study aimed to describe the clinical presentations and peculiarities of CNS infection by HpEV and EV in neonates. This is a single-center retrospective study at Istituto Gaslini, Genoa, Italy. Infants aged ≤ 30 days with a CSF RTq-PCR positive for EV or HpEV from January 1, 2022, to December 1, 2023, were enrolled. Each patient's record included demographic data, blood and CSF tests, brain MRI, therapies, length of stay, ICU admission, complications, and mortality. The two groups were compared to identify any differences and similarities. Twenty-five patients (15 EV and 10 HpEV) with a median age of 15 days were included. EV patients had a more frequent history of prematurity/neonatal respiratory distress syndrome (p = 0.021), more respiratory symptoms on admission (p = 0.012), and higher C-reactive protein (CRP) levels (p = 0.027), whereas ferritin values were significantly increased in HpEV patients (p = 0.001). Eight patients had a pathological brain MRI, equally distributed between the two groups. Three EV patients developed myocarditis and one HpEV necrotizing enterocolitis with HLH-like. No deaths occurred. Conclusion: EV and HpEV CNS infections are not easily distinguishable by clinical features. In both cases, brain MRI abnormalities are not uncommon, and a severe course of the disease is possible. Hyper-ferritinemia may represent an additional diagnostic clue for HpEV infection, and its monitoring is recommended to intercept HLH early and initiate immunomodulatory treatment. Larger studies are needed to confirm our findings. What is Known: • Parechovirus and Enteroviruses are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants. • The clinical course and distinguishing features of Parechovirus and Enterovirus central nervous system infections are not well described. What is New: • Severe disease course, brain MRI abnormalities, and complications are not uncommon in newborns with Parechovirus and Enteroviruses central nervous system infections. • Hyper-ferritinemia may represent an additional diagnostic clue for Parechovirus infection and its monitoring is recommended.
Topics: Humans; Enterovirus Infections; Male; Retrospective Studies; Female; Parechovirus; Infant, Newborn; Picornaviridae Infections; Enterovirus; Italy; Central Nervous System Infections; Magnetic Resonance Imaging
PubMed: 38492030
DOI: 10.1007/s00431-024-05518-2 -
Nature Communications Mar 2024SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which...
SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants.
Topics: Humans; SARS-CoV-2; COVID-19; HIV Infections; Antibodies, Neutralizing; Antibodies, Viral
PubMed: 38491050
DOI: 10.1038/s41467-024-46673-2 -
Pediatric Emergency Care Jun 2024The aim of the present study is to evaluate the necessity of performing lumbar puncture in patients experiencing febrile seizures, considering the epidemiology specific...
OBJECTIVE
The aim of the present study is to evaluate the necessity of performing lumbar puncture in patients experiencing febrile seizures, considering the epidemiology specific to Brazil.
METHODS
A retrospective cross-sectional study was performed from January 2017 to December 2021.
RESULTS
A total of 469 children with seizure and fever were analyzed. The identified event was the first in 65.9% (n = 309). A total of 54.2% (n = 254) of patients had a simple febrile seizure. Infectious focus, excluding previous central nervous system (CNS) infection, was identified in 35.6% (n = 167) patients. Meningitis was identified in 7.7% (n = 36) patients, all of them were viral. Patients with CNS infection had a higher frequency of symptoms such as nausea and vomiting, drowsiness, headache, and higher level of leukocytosis. A longer duration of fever was found to be more strongly associated with CNS infection.
CONCLUSIONS
When considering the use of lumbar puncture in febrile seizure, it is important to conduct a comprehensive evaluation that considers multiple factors, including clinical signs, symptoms, and the overall clinical context. Meningeal signs may be less prominent, and other symptoms such as lethargy, irritability, and vomiting may serve as more reliable indicators. Although clinical examination suggestive of meningitis remains an important factor, the recurrence of febrile seizures and a longer length of fever can provide additional insights and aid in decision-making regarding lumbar puncture.
Topics: Humans; Seizures, Febrile; Retrospective Studies; Male; Female; Cross-Sectional Studies; Child, Preschool; Infant; Risk Factors; Spinal Puncture; Central Nervous System Infections; Brazil; Child; Fever
PubMed: 38478927
DOI: 10.1097/PEC.0000000000003158 -
JAC-antimicrobial Resistance Apr 2024To determine the percentage of patients across Ireland who are discharged from the Emergency Department (ED) with an antimicrobial prescription, the indication,...
OBJECTIVES
To determine the percentage of patients across Ireland who are discharged from the Emergency Department (ED) with an antimicrobial prescription, the indication, classification of infections, and guideline compliance. To identify potential areas for antimicrobial stewardship (AMS) interventions in the ED.
PATIENTS AND METHODS
A multicentre, prospective cohort analysis study in EDs across eight hospitals in Ireland. At each site, patients aged 1 month and older who presented to the ED and were discharged directly from the ED were included. A random selection of records of patients discharged from the ED were reviewed until a minimum of 30 records with an infection diagnosis resulting in an antibiotic prescription were obtained per hospital. The number of patient discharges with no antibiotic prescriptions were included to calculate the denominator. The indication, infection classification and guideline compliance data were collected on the 30 prescriptions in the participating hospitals.
RESULTS
A total of 2619 patient records were reviewed. Of these, 249 (9.5%) patients were discharged with antimicrobial prescriptions from the ED. Most (158; 63%) were classified as probable bacterial infection, 21 (8%) as probable viral, and 18 (7%) had no documented evidence of infection. Three indications accounted for 73% of antimicrobial prescriptions: skin/soft tissue infection; ear, nose and throat infection; and urinary tract infection. Overall guideline compliance was 64%.
CONCLUSIONS
Several areas for AMS interventions to optimize antimicrobial prescribing in the ED were identified, including targeted local and national guideline reviews, delayed prescribing, improved point-of-care testing and prescriber and patient education.
PubMed: 38476772
DOI: 10.1093/jacamr/dlae038 -
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