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Zain Alamarat,1 Rodrigo Hasbun2 1Division of Infectious Diseases, Department of Pediatrics, UT Health, McGovern Medical School, Houston, TX, USA; 2Division of Infectious Diseases, Department of Internal Medicine, UT Health, McGovern Medical School, Houston, TX, USACorrespondence: Rodrigo HasbunDepartment of Internal Medicine, UT Health, McGovern Medical School, 6431 Fannin St. MSE 226, Houston, TX 77030, USATel +1 (713) 500-7140Fax +1 (713) 500-5495Email Rodrigo.Hasbun@uth.tmc.eduAbstract: Acute community-acquired bacterial meningitis (ABM) in children continues to have high rates of neurological morbidity and mortality despite the overall declining rates of infection attributed to the use of vaccines and intrapartum Group B Streptococcus prophylaxis. Prompt diagnosis and early antibiotic therapy are crucial and should not be delayed to obtain cranial imaging. Differentiating bacterial from viral meningitis continues to be a clinical dilemma especially in patients with previous antibiotic exposure. Clinical models and inflammatory biomarkers can aid clinicians in their diagnostic approach. Multiplex polymerase chain reaction and metagenomic next-generation sequencing are promising tools that can help in early and accurate diagnosis. This review will present the epidemiology of ABM in children, indications of cranial imaging, role of different models and serum biomarkers in diagnosing ABM, and management including the use of adjunctive therapies and methods of prevention.Keywords: management, CNS infection, meningitis, bacterial meningitis, children

Droughts driven by global change are triggering worldwide forest dieback, a phenomenon that is predicted to worsen. We combined genome-wide single nucleotide polymorphisms (SNPs) and dendrochronological approaches to assess genetically-based individual tree vulnerability to past extreme droughts that caused massive mortality of coihue (Nothofagus dombeyi (Mirb.) Blume) forests in northern Patagonia, Argentina. We collected fresh leaves and wood cores from pairs of trees, one with a healthy crown (HC) and another with a partially affected crown (PA), at four sites impacted by droughts in 1998, 2008, and 2014. We used dendrochronological techniques to estimate parameters in terms of growth trends due to drought and genomic analysis to assess the relationship of genomic variation with water stress. While 5155 neutral loci did not differentiate PA from HC trees, a set of 33 adaptive SNPs did, 8 of which were related to water stress. Association analysis between genomic variants and dendrophenotypic traits yielded 6 SNPs that were associated with a growth measure as resilience to cope with drought. Our preliminary results indicate that susceptibility to drought in N. dombeyi could be determined at the genomic level. The combination of these approaches provides a framework for the identification and analysis of candidate genes for stress response in non-model species. Key words: resilience, dendrophenotypes, tree genomics, hydric stress, SNPs., Resume : Les secheresses entrainees par le changement climatique global provoquent le deperissement des forets dans le monde, un phenomene qui devrait s'accentuer encore davantage. Dans cette etude, nous avons [...]

Skin biopsy demonstrates spirochetes on I Treponema pallidum i immunohistochemistry stain (Figure 1E). Skin biopsy demonstrates spirochetes on Treponema pallidum immunohistochemistry stain (E, black arrow). [Extracted from the article]

Introduction: Ventriculitis, characterized by inflammation of the ventricles in the brain, frequently occurs as a complication of neurosurgical interventions such as the insertion of cerebrospinal fluid (CSF) shunts or external ventricular drains. It can also present as a community-acquired pathology, broadening its clinical significance and complicating diagnosis and treatment. This condition presents significant challenges, primarily due to its association with various medical devices and the predisposing conditions of patients which enhance infection risks., Areas Covered: The review comprehensively explores the etiology, risk factors, diagnostic methodologies, and treatment options for ventriculitis. A thorough literature search was conducted, focusing on recent studies, meta-analyses, and clinical reports that discuss the incidence rates, the effectiveness of different management strategies, and the impact of device-related and community-acquired infections. Particular attention is given to the role of CSF drains and shunts, biofilms, and the prophylactic measures employed in clinical settings to mitigate infection risks., Expert Opinion: Despite advances in medical technology and infection control protocols, ventriculitis remains a severe complication in both neurosurgical and community settings. The review highlights the need for continued research into innovative diagnostic tools and more effective infection control strategies.

Background: Early diagnosis of encephalitis involves identifying signs of neuroinflammation, including cerebrospinal fluid (CSF) pleocytosis. However, absence of CSF pleocytosis in encephalitis has been described, most notably in autoimmune encephalitis. We examined clinical characteristics and outcomes associated with the absence or presence of CSF white blood cell pleocytosis (≥ 5 cells/µL), to inform timely diagnosis and management of encephalitis., Methods: This retrospective study compares initial CSF profiles in 597 adult patients with all-cause encephalitis., Results: Of the 597 patients, 446 (74.7%) had CSF pleocytosis while 151 (25.3%) did not. CSF pleocytosis occurred more commonly in infectious cases (200/446, 44.8%), along with 59 (13.2%) autoimmune cases, comprised chiefly of anti-NMDAR encephalitis (37/59, 62.7%). Notably, the group without pleocytosis was comprised of similar proportions of infectious (47/151, 31.1%) and autoimmune (38/151, 25.92%; p>0.05) encephalitis. Among those with infectious encephalitis, 47/247 (19%) had absent pleocytosis, including 18/76 (23.7%) with HSV-1 encephalitis. The absence of pleocytosis was associated with a decreased rate of acyclovir administration (47.7% in patients without pleocytosis vs. 71.1% in patients with pleocytosis, p<0.001). Despite pleocytosis being associated with some measures of clinical severity at admission such as a Full Outline of UnResponsiveness (FOUR) score ≤14, it was not associated with mortality or prolonged hospitalization., Conclusion: CSF pleocytosis is an important criterion for encephalitis diagnosis, but 25.3% of patients with all-cause encephalitis and 23.7% of those with HSV-1 encephalitis exhibit absence of pleocytosis on initial LP. Acyclovir initiation should not be delayed in the absence of pleocytosis in patients with suspected encephalitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Human herpesviruses (HHVs) cause a wide variety of central nervous system (CNS) infections including meningitis and encephalitis. While HHV-8 is not typically associated with neurological diseases, several studies have indicated a relationship, such as secondary central nervous system (CNS) metastases and a few isolated cases of HHV-8 encephalitis in acquired immunodeficiency syndrome (HIV). However, it has not been previously linked to encephalitis in solid organ transplantation (SOT). This case presents the first-ever instance of HHV-8 encephalitis in a SOT recipient. Our case highlights the association of HHV-8-related diseases, such as post-transplant Kaposi's Sarcoma (KS), with encephalitis. The patient was diagnosed with KS before developing neurological symptoms and received a prompt clinical response through intravenous foscarnet and ganciclovir treatment for 14 days. It is important to note that HHV-8 is a rare cause of encephalitis, and diagnosis requires a high index of suspicion in the appropriate clinical context, allowing for the use of antiviral therapy. This case also underscores the importance of considering the possibility of HHV-8-related diseases in SOT recipients, as they are at risk of developing such infections., (© 2024 Wiley Periodicals LLC.)

Background: Timely intensive care unit (ICU) admission for patients with encephalitis is associated with better prognosis. Therefore, our aim was to create a risk score predicting ICU admission in adults with encephalitis, which could aid in optimal management and resource allocation., Methods: We initially identified variables that would be most predictive of ICU admission among 372 patients with encephalitis from two hospital systems in Houston, Texas (cohort 1), who met the International Encephalitis Consortium (IEC) criteria from 2005 to 2023. Subsequently, we used a binary logistic regression model to create a risk score for ICU admission, which we then validated externally using a separate cohort of patients from two hospitals in Baltimore, Maryland (cohort 2), who met the IEC criteria from 2006 to 2022., Results: Of 634 patients with encephalitis, 255 (40%) were admitted to the ICU, including 45 of 113 (39.8%) patients with an autoimmune cause, 100 of 272 (36.7%) with an infectious cause, and 110 of 249 (44.1%) with an unknown cause (p = 0.225). After conducting a multivariate analysis in cohort 1, we found that the presence of focal neurological signs, new-onset seizure, a Full Outline of Unresponsiveness score ≤ 14, leukocytosis, and a history of chronic kidney disease at admission were associated with an increased risk of ICU admission. The resultant clinical score for predicting ICU admission had an area under the receiver operating characteristic curve (AUROC) of 0.77 (95% confidence interval [CI] 0.72-0.82, p < 0.001). Patients were classified into three risk categories for ICU admission: low risk (score 0, 12.5%), intermediate risk (scores 1-5, 49.5%), and high risk (scores 6-8, 87.5%). External validation in cohort 2 yielded an AUROC of 0.76 (95% CI 0.69-0.83, p < 0.001)., Conclusions: ICU admission is common in patients with encephalitis, regardless of etiology. Our risk score, encompassing neurologic and systemic factors, may aid physicians in decisions regarding intensity of care for adult patients with encephalitis upon hospital admission., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose of Review: Central nervous system (CNS) infections in solid organ transplant (SOT) recipients may present atypical or nonspecific symptoms. Due to a wider range of infectious agents compared with immunocompetent hosts, diagnosis is challenging. This review categorizes CNS infections in SOT recipients by cause., Recent Findings: New studies have reported new data on the epidemiology and the risk factors associated with each specific pathogen described in this review. Additionally, we included the treatment recommendations., Summary: The latest findings give us an insight into the different pathogens causing infectious neurologic complications in SOT recipients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75)., Competing Interests: A.E., T.M., K.L., M.G.T-O., R.V., C.W., Y.H., R.W.S., J.D.Z, A.J.W., A.S., C.L.C, M.M., V.E.U, S.B., K.C.M., M.T., E.A.K., J.B., T.W.G., C.H., M.G.C., D.J.H., J.J.F., M.B., A.O., J.S. have no conflicts of interest to disclose. S.A. is currently an employee of Aimmune Therapeutics, a Nestle Company. J.V.P. has been on advisory boards for Insmed, A2N, Paratek Pharmaceuticals, and Cipla Technologies, and has spoken for Insmed. M.P.V. received research funding from Paratek Pharmaceuticals, Cumberland Pharmaceuticals, Insmed, AN2, Spero, Hillrom, and Electromed. C.M-C. has consulted for HIVE Medical Inc, and has received grant funding from the CDC (CDC# 1U54CK000617-01-00). C.T.F. has spoken for Insmed. R.H. has consulted for and received research funding from Biofire Diagnostics. K.A.C. is currently employed by Janssen pharmaceutical companies of Johnson & Johnson and has received consulting fees from Insmed, Hillrom, Merck, and Microbion, and AN2, unrelated to the current investigation, and was supported by National Heart, Lung, and Blood Institute K08 HL1139994 and the Burroughs Welcome Fund Career Award for Medical Scientists. M.J.R. has received funds for research and consulting or participated in speaking bureaus for Abbvie, Baselia, Ferring, Melinta, Merck, Paratek Pharmaceuticals, Shionogi, Tetraphase, and T2 Biosystems and is partially supported by National Institute of Allergy and Infectious Diseases R21 AI163726. Conflicts that the editors considered relevant to the content of the manuscript have been disclosed.

Background: Updating live vaccines such as measles, mumps, rubella, and varicella (MMRV) is an important step in preparing patients for solid organ transplant (SOT) to prevent morbidity from these preventable diseases. However, data for this approach are scarce. Thus, we aimed to describe the seroprevalence of MMRV and the efficacy of the vaccines in our transplant center., Methods: Pre-SOT candidates >18 y of age were retrospectively retrieved from SOT database in Memorial Hermann Hospital Texas Medical Center. MMRV serologies are routinely screened at the time of pretransplant evaluation. We divided patients into 2 groups: MMRV-positive group versus MMRV-negative group, patients with positive all MMRV serologies and with negative immunity to at least 1 dose of MMRV, respectively., Results: A total of 1213 patients were identified. Three hundred ninety-four patients (32.4%) did not have immunity to at least 1 dose of MMRV. Multivariate analysis was conducted. Older age (odds ratio [OR]: 1.04) and liver transplant candidates (OR: 1.71) were associated with seropositivity. Previous history of SOT (OR: 0.54) and pancreas/kidney transplant candidates (OR: 0.24) were associated with seronegativity. Among 394 MMRV seronegative patients, 60 patients received 1 dose of MMR vaccine and 14 patients received 1 dose of varicella-zoster virus vaccine without severe adverse events. A total of 35% (13/37) of patients who had follow-up serologies did not have a serological response., Conclusions: A significant number of pre-SOT candidates were not immune to at least 1 dose of MMRV. This highlights the importance of MMRV screening and vaccinations pre-SOT. Postvaccination serological confirmation should be performed to evaluate the necessity for a second dose., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Encephalitis presents with high morbidity and mortality in both HIV-infected and HIV-negative patients. There are currently no studies comparing HIV-infected and HIV-negative patients admitted to the hospital with acute encephalitis., Methods: We conducted a multicenter, retrospective study of adults admitted to the hospital with a diagnosis of encephalitis in Houston, Texas between 2005 and 2020. We describe the clinical manifestations, etiology, and outcomes of these patients with a focus on those infected with HIV., Results: We identified 260 patients with encephalitis, 40 of whom were infected with HIV. Viral etiology was identified in 18 of the 40 HIV-infected patients (45.0%); bacterial in 9 (22.5%); parasitic in 5 (12.5%); fungal in 3 (7.5%); immune-mediated in 2 (5.0%). Eleven cases had unclear etiology (27.5%). More than one disease process was identified in 12 (30.0%) patients. HIV-infected persons were more likely to have neurosyphilis (8/40 vs. 1/220; OR 55; 95%CI 6.6-450), CMV encephalitis [5/18 vs. 1/30; OR 11.2 (1.18-105)], or VZV encephalitis (8/21 vs. 10/89; OR 4.82; 1.62-14.6) compared to the HIV-negative patients. Inpatient mortality was similar in the HIV-infected and HIV-negative patients, 15.0% vs 9.5% [p = 0.4, OR 1.67 (0.63-4.44)], but one-year mortality was higher for the HIV-infected patients, 31.3% vs 16.0% [p = 0.04, OR 2.40 (1.02-5.55)]., Conclusion: This large, multicenter study shows that HIV-infected patients with encephalitis have a distinct pattern of disease when compared with HIV-negative patients, and that this population has nearly twice the odds of mortality in the year following hospitalization., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE., Methods: We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1., Results: We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected (p = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown., Conclusions: Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit., (© 2023. The Author(s).)

Purpose of Review: The most common infectious etiologies of meningitis and encephalitis are viruses. In this review, we will discuss current epidemiology, prevention, diagnosis, and treatment of the most common causes of viral meningitis and encephalitis worldwide., Recent Findings: Viral meningitis and encephalitis are increasingly diagnosed as molecular diagnostic techniques and serologies have become more readily available worldwide but recent progress in novel antiviral therapies remains limited. Emerging and re-emerging viruses that have caused endemic or worldwide outbreaks or epidemics are arboviruses (e.g., West Nile virus, Japanese encephalitis, Tick borne encephalitis, Dengue, Zika, Toscana), enteroviruses (e.g., Enterovirus 71, Enterovirus D68), Parechoviruses, respiratory viruses [e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, metapneumoviruses, measles, mumps], and herpes viruses [e.g., herpes simplex virus (HSV) type 1 (HSV-1), HSV-2, human herpes (HV) 6, varicella zoster virus (VZV)]. Future efforts should concentrate in increasing availability for those viruses with effective vaccination [e.g., Japanese encephalitis, Tick borne encephalitis, varicella zoster viruses, SARS-CoV-2, influenza], prompt initiation of those with encephalitis with treatable viruses (e.g., HSV-1, VZV), increasing the diagnostic yield by using novel techniques such as metagenomic sequencing and avoiding unnecessary antibiotics in those with viral meningitis or encephalitis., Summary: We review the current epidemiology, clinical presentation, diagnosis, and treatment of the common causative agents of viral meningitis and encephalitis worldwide., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)