Central Nervous System Infection Research Articles

Simultaneous post-neurosurgical ventriculitis and bacteraemia by two different strains of KPC-producing K. pneumoniae successfully treated with meropenem/vaborbactam and high dose of fosfomycin

ObjectiveA case of post-neurosurgical ventriculitis caused by a KPC-producing Klebsiella pneumoniae (KPC-Kp) with a ceftazidime/avibactam-resistant, meropenem-susceptible phenotype is reported. Methods and resultsThe patient had a concomitant bloodstream infection with a wild-type KPC-Kp with a ceftazidime/avibactam-susceptible, meropenem-resistant phenotype. Prolonged treatment with intravenous fosfomycin and meropenem/vaborbactam achieved clinical success.Therapeutic drug monitoring performed during the first days of treatment showed for the first time that vaborbactam efficiently penetrates cerebrospinal fluid. In contrast, meropenem was undetectable in cerebrospinal fluid at each sampling, suggesting that additional doses of meropenem may be required to appropriately prescribe meropenem/vaborbactam for central nervous system infections. Plasma and cerebrospinal fluid levels of fosfomycin were adequate, confirming the potential of this agent possibly even in the fight against multidrug-resistant organisms. ConclusionsThis case highlights the need for therapeutic drug monitoring as a crucial tool for optimizing treatment in complicated cases where the pharmacokinetic behaviour of antibiotics is difficult to predict.

Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing*

ObjectiveViral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. MethodsWe designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. ResultsThe results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. ConclusionAmplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.

Combination of metagenomic next-generation sequencing and conventional tests unraveled pathogen profiles in infected patients undergoing allogeneic hematopoietic stem cell transplantation in Jilin Province of China.

Infection is the main cause of death for patients after allogeneic hematopoietic stem cell transplantation (HSCT). However, pathogen profiles still have not been reported in detail due to their heterogeneity caused by geographic region. To evaluate the performance of metagenomic next-generation sequencing (mNGS) and summarize regional pathogen profiles of infected patients after HSCT. From February 2021 to August 2022, 64 patients, admitted to the Department of Hematology of The First Hospital of Jilin University for HSCT and diagnosed as suspected infections, were retrospectively enrolled. A total of 38 patients were diagnosed as having infections, including bloodstream (n =17), pulmonary (n =16), central nervous system (CNS) (n =4), and chest (n =1) infections. Human betaherpesvirus 5 (CMV) was the most common pathogen in both bloodstream (n =10) and pulmonary (n =8) infections, while CNS (n =2) and chest (n =1) infections were mainly caused by Human gammaherpesvirus 4 (EBV). For bloodstream infection, Mycobacterium tuberculosis complex (n =3), Staphylococcus epidermidis (n =1), and Candida tropicalis (n =1) were also diagnosed as causative pathogens. Furthermore, mNGS combined with conventional tests can identify more causative pathogens with high sensitivity of 82.9% (95% CI 70.4-95.3%), and the total coincidence rate can reach up to 76.7% (95% CI 64.1-89.4%). Our findings emphasized the importance of mNGS in diagnosing, managing, and ruling out infections, and an era of more rapid, independent, and impartial diagnosis of infections after HSCT can be expected.

Fusarium species central nervous system infection.

Fusarium species are an increasingly important cause of meningitis and invasive disease in immunocompromised patients as well as in otherwise healthy patients as observed in two recent healthcare-associated outbreaks. This review summarizes recently published information on treatment and diagnosis of this infection. Incidence of Fusarium species meningitis and invasive fusariosis are increasing. Molecular techniques are improving the speed of diagnosis. New antifungal agents in development show good in vitro activity against some Fusarium species. New technologies, including cerebrospinal fluid (CSF) filtration, may play a role in treatment of central nervous system (CNS) disease. Due to the continued prime importance of the host immune system in recovery, immunomodulatory treatments may play a role in treatment. The overall incidence of CNS fusariosis is increasing with a continued poor prognosis, but new diagnostic and treatment modalities are in development which may offer improvements.

Clinical course and peculiarities of Parechovirus and Enterovirus central nervous system infections in newborns: a single-center experience.

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 ≤ 30days 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 15days 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.

Characteristics and Risk Factors of Central Nervous System Infection in Children With Febrile Seizures.

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. A retrospective cross-sectional study was performed from January 2017 to December 2021. 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. 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.

The associations of herpes simplex virus and varicella zoster virus infection with dementia: a nationwide retrospective cohort study

BackgroundIn this study, the risk of dementia in patients with a history of herpes simplex virus (HSV) or varicella zoster virus (VZV) infection was evaluated.MethodsThis nationwide cohort study used data from the Korean National Health Insurance Service collected between 2006 and 2017. A total of 752,205 subjects ≥ 45 years of age not diagnosed with dementia until 2006 were included. A multivariate Cox regression model, adjusted for age, sex, and other comorbidities, was used to assess the hazard ratio (HR) for dementia based on VZV or HSV infection. The interaction effects of both viral infections were analysed. Viral infections are classified into four categories: eye, central nervous system (CNS), simple, and complicated. The hazard ratio (HR) of viral infection was analysed based on the type of dementia.ResultsIn multivariable analysis, both HSV and VZV infection were associated with an increased risk of dementia (HR = 1.38, 95% confidence interval, CI:1.33–1.43) and (HR = 1.41, 95% CI:1.37–1.46), respectively. Patients who experienced both HSV and VZV infections were also at an increased risk of dementia (HR = 1.57, 95% CI:1.50–1.63). The co-infection group showed the shortest time from viral infection to dementia diagnosis (4.09 ± 3.02 years). In the subgroup analysis, all types of HSV and VZV infections were associated with an increased risk of dementia compared to the non-infection group. The eye, CNS, and complicated VZV infections were associated with a significantly higher risk than simple VZV infections. There were no significant differences between the subtypes of HSV infection. Furthermore, HSV, VSV, and co-infection were associated with an increased risk of all dementia types, including Alzheimer’s disease (AD) and vascular dementia (VD).ConclusionsIndividual HSV and VZV infections were associated with an increased risk of all types of dementia, including AD and VD. Patients co-infected with HSV and VZV, VZV infection in the eye, CNS, or complicated type were more vulnerable to the development of dementia.

CD4 Count and Central Nervous System Infection among HIV/AIDS Patients in an Indonesian Presidential Hospital from 2020 to 2022

CD4 Count and Central Nervous System Infection among HIV/AIDS Patients in an Indonesian Presidential Hospital from 2020 to 2022

Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM).

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by experts in both adult and pediatric laboratory and clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including arboviral Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also addressed. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

Ceftaroline for Central Nervous System Infections: Case Report of a Young Infant, and Scoping Review.

Managing health care acquired and device-associated intracranial infections in young children can be challenging given adverse antibiotic side effects and difficulties in achieving adequate central nervous system (CNS) antibiotic concentrations. Ceftaroline is a cephalosporin with a favorable safety profile and activity against methicillin-resistant Staphylococci and several Gram-negative organisms. Published data on the use of ceftaroline for CNS infections in children and adults are limited. We describe a 2-month-old infant with ventriculo-subgaleal shunt-associated methicillin-resistant Staphylococcus epidermidis ventriculitis, which was successfully treated with ceftaroline, in addition to vancomycin and rifampin. We conducted a scoping review of English-language literature retrieved from PubMed, EMBASE and Web of Science that assessed the use of ceftaroline for CNS infections. We identified 22 articles for inclusion in our review, which described 92 unique patients, of whom 2 were <21 years old. Ceftaroline was commonly used in conjunction with other antibiotics to treat infections caused by Staphylococcus aureus, coagulase-negative Staphylococci and Streptococcus pneumoniae. Most case reports described clinical success with ceftaroline, though small case series and cohort studies yielded mixed efficacy assessments. Adverse effects attributed to ceftaroline were rare and included reversible myelosuppression, eosinophilia, hepatotoxicity and nephrotoxicity. Pharmacokinetic/pharmacodynamic studies suggested similar CNS penetration through inflamed meninges as other beta lactam antibiotics. We identified a growing body of published evidence supporting the use of ceftaroline in combination with other agents for the treatment of CNS infections. In absence of clinical trials, additional real-world data are needed to define the efficacy and safety of ceftaroline for children and adults with CNS infections.

Application of metagenomic next-generation sequencing in the clinical diagnosis of infectious diseases after allo-HSCT: a single-center analysis

BackgroundWe investigated the value of metagenomic next-generation sequencing (mNGS) in diagnosing infectious diseases in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsFifty-four patients who had fever following allo-HSCT from October 2019 to February 2022 were enrolled. Conventional microbiological tests (CMTs) and mNGS, along with imaging and clinical manifestations, were used to diagnose infection following allo-HSCT. The clinical diagnostic value of mNGS was evaluated.ResultsA total of 61 mNGS tests were performed, resulting in the diagnosis of 46 cases of infectious diseases. Among these cases, there were 22 cases of viral infection, 13 cases of fungal infection, and 11 cases of bacterial infection. Moreover, 27 cases (58.7%) were classified as bloodstream infections, 15 (32.6%) as respiratory infections, 2 (4.3%) as digestive system infections, and 2 (4.3%) as central nervous system infections. Additionally, there were 8 cases with non-infectious diseases (8/54, 14.81%), including 2 cases of interstitial pneumonia, 2 cases of bronchiolitis obliterans, 2 cases of engraftment syndrome, and 2 cases of acute graft-versus-host disease. The positive detection rates of mNGS and CMT were 88.9% and 33.3%, respectively, with significant differences (P < 0.001). The sensitivity of mNGS was 97.82%, the specificity was 25%, the positive predictive value was 93.75%, and the negative predictive value was 50%. Following treatment, 51 patients showed improvement, and 3 cases succumbed to multidrug-resistant bacterial infections.ConclusionsmNGS plays an important role in the early clinical diagnosis of infectious diseases after allo-HSCT, which is not affected by immunosuppression status, empiric antibiotic therapy, and multi-microbial mixed infection.

Human herpesvirus-6 infection in a critically ill and immunocompetent patient: a case report

BackgroundHuman herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series.Case PresentationIn this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively.ConclusionThis case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient.

Early Initiation of Antiretroviral Therapy is Protective Against Seizures in Children With HIV in Zambia: A Prospective Case-Control Study.

Seizures are relatively common among children with HIV in low- and middle-income countries and are associated with significant morbidity and mortality. Early treatment with antiretroviral therapy (ART) may reduce this risk by decreasing rates of central nervous system infections and HIV encephalopathy. We conducted a prospective, unmatched case-control study. We enrolled children with new-onset seizure from University Teaching Hospital in Lusaka, Zambia and 2 regional hospitals in rural Zambia. Controls were children with HIV and no history of seizures. Recruitment took place from 2016 to 2019. Early treatment was defined as initiation of ART before 12 months of age, at a CD4 percentage >15% in children aged 12-60 months or a CD4 count >350 cells/mm 3 for children aged 60 months or older. Logistic regression models were used to evaluate the association between potential risk factors and seizures. We identified 73 children with new-onset seizure and compared them with 254 control children with HIV but no seizures. Early treatment with ART was associated with a significant reduction in the odds of seizures [odds ratio (OR) 0.04, 95% confidence interval: 0.02 to 0.09; P < 0.001]. Having an undetectable viral load at the time of enrollment was strongly protective against seizures (OR 0.03, P < 0.001), whereas history of World Health Organization Stage 4 disease (OR 2.2, P = 0.05) or CD4 count <200 cells/mm 3 (OR 3.6, P < 0.001) increased risk of seizures. Early initiation of ART and successful viral suppression would likely reduce much of the excess seizure burden in children with HIV.

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

BackgroundEarly and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR).MethodsThis study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization.Results53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0–63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 − 84.1%), 76.0% (95%CI: 56.6 − 88.5%), 77.8% (59.2 − 89.4%) and 85.2% (95%CI: 67.5 − 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay.ConclusionsNTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.

Changing rates but persisting seasons: patterns of enterovirus infections in hospitalizations and outpatient visits in Denmark 2015-2022

BackgroundEnteroviruses (EV) constitute a diverse group of viruses manifesting a broad spectrum of clinical presentations in humans ranging from mild skin manifestations to more severe central nervous system (CNS) infection. Severe infections are reported with increased frequency globally, albeit the burden of diseases and the evolution of circulating viruses is largely unknown. We aimed to systematically explore contemporary trends in hospitalizations attributed to EV infections using national hospitalization discharge data.MethodsWe utilized the Danish National Patient Register which holds information on all contacts to Danish hospitals. We covered eight full years (2015-2022). Length-of-stay and administrative procedure codes were used to distinguish hospital admissions from outpatient visits. We utilized burden of disease estimates and distribution statistics.ResultsWe identified 1029 hospitalizations and 1970 outpatient visits due to EV infections. The hospital admissions were primarily associated with CNS-infections (n=570, 55.4%) and skin (n=252, 24.5%), with variation over the studied period. The admitted patients were predominately children (43.8%) though patients were identified in all ages. The clinical manifestation was associated with age, with CNS infections dominating in the neonates and adults, and skin infections dominating in children 1-2 years (17.2%). Outpatient visits were predominantly observed among children 1-2 years (55.0%), presenting with skin symptoms (77.9%). We show a seasonal pattern of EV infections with summer/fall peaks and markedly impact on the EV hospitalization burden related to COVID-19 mitigation measures including national lockdown periods. 25% of hospital admissions occurred during 2020-2022.ConclusionEV infections caused both hospital admissions and outpatient visits in the period studied, predominately among children aged 1-2 years. Overall, skin infections dominated the outpatient visits, while the majority of hospital admissions were due to CNS infections. The pandemic period did not change the seasonal pattern of EV infections but notably lowered the number of admissions to hospital with CNS infection and raised the number of outpatient admissions with skin infection.

Diagnostic Stewardship in the Evaluation of a Child With a Potential Central Nervous System Infection.

Diagnostic Stewardship in the Evaluation of a Child With a Potential Central Nervous System Infection.

Human Parechovirus Meningoencephalitis In an Eight-Day-Old Infant

Human parechovirus (HPeV) infections have been increasing in the United States since May 2022, according to the Centers for Disease Control and Prevention. HPeVs are a member of the Picornaviridae family and share similarities with enteroviruses, though they differ in genomic structure. HPeV commonly affects children, with disease manifestations ranging anywhere from an asymptomatic infection to severe disease. HPeV typically affects the gastrointestinal and respiratory tracts but may rarely also cause severe infection of the central nervous system (CNS), leading to sepsis-like illness, meningitis, and encephalitis. Of the 19 established serotypes of HPeV, serotypesA1 and A3 are most commonly identified in humans. HPeV serotype A3 is of particular importance as it more commonly causes sepsis and CNS infection, especially in children. In the United States between 2014 and 2016, a total of 2758 cases of enteroviruses and parechoviruses were reported to the National Enterovirus Surveillance System. Of those cases, 2.3% were distinguished as HPeVA3. This case details the clinical course of an eight-day-old infant with HPeV meningoencephalitis. The infant initially presented with fever and other nonspecific symptoms, which later progressed to include diffuse erythroderma and seizure activity. Although current management of HPeV meningoencephalitis involves supportive care and close monitoring, determining HPeV as a cause of infection is important due to the long-term sequelae that patients may develop. Potential complications of infection include white matter lesions of the brain, cerebral palsy, developmental delay, and visual impairment. This case was documented to increase awareness of the rising incidence of HPeV infections in children in the United States, as well as to detail the signs and symptoms of HPeV meningoencephalitis in a neonate.

Pattern of Fluid Overload and its Impact on Mortality Among Mechanically Ventilated Children: Secondary Analysis of the ReLiSCh Trial.

To assess the pattern of fluid overload (FO) and its impact on mortality among mechanically ventilated children. In this secondary analysis of an open-label randomized controlled trial (ReLiSCh trial, October 2020-September 2021), hemodynamically stable mechanically ventilated children (n = 100) admitted to a tertiary level pediatric intensive care unit (PICU) in North India were enrolled. The primary outcome was pattern of FO (FO% >10% and cumulative FO% from day 1-7); and secondary outcomes were pattern of FO among survivors and non-survivors, and prescription practices of maintenance fluid. The median (IQR) age was 3.5 (0.85-7.5) y and 57% were males. Common diagnoses were pneumonia (27%), scrub typhus (14%), Landry-Guillain-Barré syndrome (9%), dengue (8%), central nervous system infections (7%) and staphylococcal sepsis (6%). Common organ dysfunction included acute respiratory distress syndrome (ARDS) (41%), shock (38%), and acute kidney injury (AKI) (9%). The duration PICU stay was 11 (7-17) d and mortality was 12%. The FO% >10% was noted in 19% children; and there was significant increase in cumulative FO% from day 1-7 [1.2 (0.2-2.6)% to 8.5 (1.7-14.3)%, (p = 0.000)]. Among non-survivors, higher proportion had FO% >10% (66.7% vs. 12.5%, p 0.0001); and trend towards higher cumulative FO% on first seven days. From day 1-7, the percentage of maintenance fluid received increased from 60 (50-71)% to 70 (60-77)% (p = 0.691). One-fifth of mechanically ventilated children had FO% >10% and there was significant increase in cumulative FO% from day 1-7. Non-survivors had significantly higher degree of FO.

Association of cesarean section and infectious outcomes among infants at 1 year of age: Logistic regression analysis using data of 104,065 records from the Japan Environment and Children's Study.

There has been a recent decrease in the prevalence of infectious diseases in children worldwide due to the usage of vaccines. However, the association between cesarean delivery and infectious diseases remains unclear. Here, we aimed to clarify the association between cesarean delivery and the development of infectious diseases. This study is a cross-sectional study. We used data from the Japan Environment and Children's Study, which is a prospective, nationwide, government-funded birth cohort study. The data of 104,065 records were included. Information about the mode of delivery, central nervous system infection (CNSI), otitis media (OM), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), gastrointestinal infection (GI), and urinary tract infection (UTI) was obtained from questionnaires and medical records transcripts. Multiple logistic regression analysis was used to assess the association between cesarean delivery and CNSI, OM, URTI, LRTI, GI, and UTI risk. We included a total of 74,477 subjects in this study, of which 18.4% underwent cesarean deliveries. After adjusting for the perinatal, socioeconomic, and postnatal confounding factors, children born by cesarean delivery did not have an increased risk of developing CNSI (95% confidence interval [CI] 0.46-1.35), OM (95% CI 0.99-1.12), URTI (95% CI 0.97-1.06), LRTI (95% CI 0.98-1.15), GI (95% CI 0.98-1.11), or UTI (95% CI 0.95-1.45). This nationwide cohort study did not find an association between cesarean delivery and CNSI, OM, URTI, LRTI, GI, and UTI. However, further studies are needed to evaluate the role of cesarean delivery in the development of infectious diseases.

Large-Scale Proteome Profiling Identifies Biomarkers Associated with Suspected Neurosyphilis Diagnosis.

Neurosyphilis (NS) is a central nervous system (CNS) infection caused by Treponema pallidum (T. pallidum). NS can occur at any stage of syphilis and manifests as a broad spectrum of clinical symptoms. Often referred to as "the great imitator," NS can be easily overlooked or misdiagnosed due to the absence of standard diagnostic tests, potentially leading to severe and irreversible organ dysfunction. In this study, proteomic and machine learning model techniques are used to characterize 223 cerebrospinal fluid (CSF) samples to identify diagnostic markers of NS and provide insights into the underlying mechanisms of the associated inflammatory responses. Three biomarkers (SEMA7A, SERPINA3, and ITIH4) are validated as contributors to NS diagnosis through multicenter verification of an additional 115 CSF samples. We anticipate that the identified biomarkers will become effective tools for assisting in diagnosis of NS. Our insights into NS pathogenesis in brain tissue may inform therapeutic strategies and drug discoveries for NS patients.