-
Journal of Neuropathology and... Mar 2024Subacute sclerosing panencephalitis (SSPE) is a fatal, slowly progressive brain disorder caused by a mutated measles virus. Both subacute inflammatory and...
Subacute sclerosing panencephalitis (SSPE) is a fatal, slowly progressive brain disorder caused by a mutated measles virus. Both subacute inflammatory and neurodegenerative mechanisms appear to play significant roles in the pathogenesis. TAR DNA-binding protein 43 (TDP-43) inclusions are a common co-pathology in several neurodegenerative disorders with diverse pathogenesis. In the present study, we examined brains of 16 autopsied SSPE patients for the presence of TDP-43 pathology and possible associations with tau pathology. Immunohistochemical staining identified TDP-43 inclusions in 31% of SSPE cases. TDP-43 pathology was widely distributed in the brains, most severely in the atrophied cerebral cortex (temporal and parietal), and most frequently as tangle- and thread-like neuronal cytoplasmic inclusions. It was associated with longer disease duration (>4 years) and tau pathology (all TDP-43-positive cases had tau-positive neurofibrillary tangles). This study demonstrates for the first time an association between TDP-43 pathology and SSPE. The co-occurrence of TDP-43 and tau aggregates and correlation with the disease duration suggest that both pathological proteins are involved in the neurodegenerative process induced by viral inflammation.
Topics: Humans; Subacute Sclerosing Panencephalitis; Measles virus; Brain; Neurofibrillary Tangles; DNA-Binding Proteins; Inflammation
PubMed: 38456313
DOI: 10.1093/jnen/nlae017 -
Indian Journal of Pathology &... Nov 2023The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate...
BACKGROUND
The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate the bacterial and viral etiological diagnosis of ME in children less than 5 years of age.
MATERIAL AND METHODS
The present study was conducted in Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, King George's Medical University, Lucknow, from July 2020 to June 2022. Serum, cerebrospinal fluid (CSF), and nose/throat swabs were collected from all the enrolled cases of meningoencephalitis in children below 5 years of age and tested for various etiological agents by ELISA and/or real-time PCR.
RESULTS
Of 130 enrolled cases, 50 (38.5%) cases tested positive for one or more etiological agents. Etiological agents of ME detected were Japanese encephalitis virus (JEV) (8.46%), adenovirus (6.92%), influenza virus (5.38%), dengue virus (3.85%), Parvo B-19 virus (3.08%), Orientia tsutsugamushi (3.08%), Herpes Simplex Virus-1 (HSV-1) (1.54%), measles virus (1.54%), and Varicella-Zoster Virus (VZV) (1.54%). Rubella virus, Chikungunya virus (CHKV), Mumps virus, Enteroviruses, Parecho virus, John Cunningham virus (JC), BK virus, Nipah virus, Kyasanur Forest Disease virus (KFD), Chandipura virus, Herpes Simplex Virus (HSV-2), SARS CoV-2, N. Meningitides, and H. Influenzae were tested but not detected in any of the cases.
CONCLUSION
We identified the etiological agents in 50/130 (38.5%) suspected ME cases in children less than 5 years of age, using molecular and ELISA-based diagnostic methods. The four most common pathogens detected were JEV, adenovirus, influenza virus, and dengue virus.
PubMed: 38394398
DOI: 10.4103/ijpm.ijpm_60_23 -
Vaccines Nov 2023Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier-to-use, and more cost-effective means for the administration of vaccines than...
Safety, Tolerability, and Immunogenicity of Measles and Rubella Vaccine Delivered with a High-Density Microarray Patch: Results from a Randomized, Partially Double-Blinded, Placebo-Controlled Phase I Clinical Trial.
Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier-to-use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blinded, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18-50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3100 median cell-culture infectious dose [CCID] measles, ~4300 CCID rubella); high-dose MR-HD-MAPs (~9300 CCID measles, ~12,900 CCID rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1000 CCID per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2-8 °C for at least 24 months. When MR HD-MAPs stored at 2-8 °C for 24 months were transferred to 40 °C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates on day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7%, respectively, for measles, and 37.5%, 25.0% and 35.7%, respectively, for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.
PubMed: 38006057
DOI: 10.3390/vaccines11111725 -
Journal of Virus Eradication Dec 2023This work sought to estimate population measles seroprevalence and heterogeneity in the antibody concentration distribution that could be explained by the birth-year...
OBJECTIVE
This work sought to estimate population measles seroprevalence and heterogeneity in the antibody concentration distribution that could be explained by the birth-year cohort according to the opportunity of viral and vaccine exposure, applied to data from Medellín, Colombia.
METHODS
Prevalence of IgG antibodies was analyzed for measles based on a population study with a random sample of 2098 individuals from 6 to 64 years of age. Finite mixture models were used to estimate global seroprevalence and that of three birth-year cohorts (I: born up to 1982; II: 1983-1994; III: born since 1995). Multiple linear regression permitted adjusting the concentration of antibodies by cohort, zone, and sex.
RESULTS
Globally, seronegativity was 6.5% (95% CI 4.9- 8.6), seropositivity of 78.4% (95% CI 75.1-81.4), and equivocal of 15.1% (95% CI 12.5-18.1). Two components were found with skewed normal distribution, which reclassified those equivocal as seropositive. Differences were observed by cohort in the geometric mean of antibodies [Cohort I: 1704.6; II: 562.2; III: 802.1 milli-international units per milliliter (mIU/mL] and seronegativity (Cohort I: 4%; II:13.3%; III: 8.9%). Antibody concentration increased by 1.26 mIU/mL in residents in the rural area, while diminishing in individuals from cohort II (by 3.02 mIU/mL) and cohort III (by 2.14 mIU/mL).
CONCLUSION
The younger cohorts (II and III) had a lower antibody concentration (higher seronegativity), indicating the need to monitor periodically seroprevalence and an eventual reestablishment of the transmission in these groups with higher risk of infection.
PubMed: 38046787
DOI: 10.1016/j.jve.2023.100352 -
Medical Science Monitor : International... Feb 2024In December 2023, the US Centers for Disease Control and Prevention (CDC) published the updated 2024 Advisory Committee on Immunization Practices (ACIP) Adult...
Editorial: Global Health Concerns as Vaccine-Preventable Infections Including SARS-CoV-2 (JN.1), Influenza, Respiratory Syncytial Virus (RSV), and Measles Continue to Rise.
In December 2023, the US Centers for Disease Control and Prevention (CDC) published the updated 2024 Advisory Committee on Immunization Practices (ACIP) Adult Immunization Schedule, which is available online for access by the public and healthcare professionals. These new guidelines come at a time when the incidence of vaccine-preventable viral infections from SARS-CoV-2 (JN.1), respiratory syncytial virus (RSV), influenza, and measles are increasing in adults and children due to vaccine hesitancy, or non-compliance. This editorial aims to highlight the ongoing global health concerns for the consequences of increasing reports of vaccine-preventable infections, including SARS-CoV-2 (JN.1), influenza, RSV, and measles, to understand the causes of vaccine hesitancy, and introduce some public health measures that could improve vaccine uptake.
Topics: Child; Adult; Humans; Influenza, Human; SARS-CoV-2; Respiratory Syncytial Viruses; Global Health; COVID-19; Influenza Vaccines; Measles; Communicable Diseases
PubMed: 38298093
DOI: 10.12659/MSM.943911 -
Journal of Virology Oct 2023For many years, measles virus (MeV) was assumed to first enter the host via the apical surface of airway epithelial cells and subsequently spread systemically. We and...
For many years, measles virus (MeV) was assumed to first enter the host via the apical surface of airway epithelial cells and subsequently spread systemically. We and others reported that MeV has an overwhelming preference for entry at the basolateral surface of airway epithelial cells, which led to a fundamental new understanding of how MeV enters a human host. This unexpected observation using well-differentiated primary cultures of airway epithelia from human donors contradicted previous studies using immortalized cultured cells. Here, we show that appropriate differentiation and cell morphology of primary human airway epithelial cells are critical to recapitulate MeV infection patterns and pathogenesis of the airways. By simply culturing primary cells in media containing serum or passaging primary cultures, erroneous results quickly emerge. These results have broad implications for data interpretation related to respiratory virus infection, spread, and release from human airway epithelial cells.
Topics: Humans; Cells, Cultured; Epithelial Cells; Epithelium; Measles; Measles virus; Respiratory System
PubMed: 37732787
DOI: 10.1128/jvi.01051-23 -
Frontiers in Immunology 2023In the vaccine era, individuals receive multiple vaccines in their lifetime. Host gene expression in response to antigenic stimulation is usually virus-specific;...
BACKGROUND
In the vaccine era, individuals receive multiple vaccines in their lifetime. Host gene expression in response to antigenic stimulation is usually virus-specific; however, identifying shared pathways of host response across a wide spectrum of vaccine pathogens can shed light on the molecular mechanisms/components which can be targeted for the development of broad/universal therapeutics and vaccines.
METHOD
We isolated PBMCs, monocytes, B cells, and CD8 T cells from the peripheral blood of healthy donors, who received both seasonal influenza vaccine (within <1 year) and smallpox vaccine (within 1 - 4 years). Each of the purified cell populations was stimulated with either influenza virus or vaccinia virus. Differentially expressed genes (DEGs) relative to unstimulated controls were identified for each viral infection, as well as for both viral infections (shared DEGs). Pathway enrichment analysis was performed to associate identified DEGs with KEGG/biological pathways.
RESULTS
We identified 2,906, 3,888, 681, and 446 DEGs in PBMCs, monocytes, B cells, and CD8 T cells, respectively, in response to influenza stimulation. Meanwhile, 97, 120, 20, and 10 DEGs were identified as gene signatures in PBMCs, monocytes, B cells, and CD8 T cells, respectively, upon vaccinia stimulation. The majority of DEGs identified in PBMCs were also found in monocytes after either viral stimulation. Of the virus-specific DEGs, 55, 63, and 9 DEGs occurred in common in PBMCs, monocytes, and B cells, respectively, while no DEGs were shared in infected CD8 T cells after influenza and vaccinia. Gene set enrichment analysis demonstrated that these shared DEGs were over-represented in innate signaling pathways, including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, Toll-like receptor signaling, RIG-I-like receptor signaling pathways, cytosolic DNA-sensing pathways, and natural killer cell mediated cytotoxicity.
CONCLUSION
Our results provide insights into virus-host interactions in different immune cells, as well as host defense mechanisms against viral stimulation. Our data also highlights the role of monocytes as a major cell population driving gene expression in PBMCs in response to viral stimulation. The immune response signaling pathways identified in this study may provide specific targets for the development of novel virus-specific therapeutics and improved vaccines for vaccinia and influenza. Although influenza and vaccinia viruses have been selected in this study as pathogen models, this approach could be applicable to other pathogens.
Topics: Humans; Vaccinia; Vaccinia virus; Influenza, Human; Influenza Vaccines; CD8-Positive T-Lymphocytes; Transcriptome; Vaccination
PubMed: 37600811
DOI: 10.3389/fimmu.2023.1168784 -
Ocular Immunology and Inflammation Sep 2023We provide an updated review of pre-selected RNA viruses causing ocular inflammation in humans. RNA viruses such as coronaviruses and arboviruses are reviewed elsewhere.... (Review)
Review
We provide an updated review of pre-selected RNA viruses causing ocular inflammation in humans. RNA viruses such as coronaviruses and arboviruses are reviewed elsewhere. A Google Scholar search was conducted to identify recent publications on ocular inflammation caused by the RNA viruses specified here. Human RNA viruses target a wide range of ocular tissues from the anterior to the posterior. Influenza, measles and mumps cause anterior segment manifestations including conjunctivitis and keratitis, while retinitis and optic neuritis may be seen posteriorly. Newcastle disease and RSV cause conjunctivitis, whereas HIV causes characteristic anterior uveitis. Cataracts, microphthalmos, and iris abnormalities are common in congenital Rubella, while Rubella virus is associated with Fuchs uveitis syndrome. Newer technologies make it possible to detect more than one pathogen if present simultaneously. RNA viruses may produce significant ocular morbidity, and care should be taken to investigate ocular symptoms during disease outbreaks.
Topics: Animals; Humans; Coronavirus; Arboviruses; Coronavirus Infections; Inflammation; Conjunctivitis; T-Lymphocytes
PubMed: 37315305
DOI: 10.1080/09273948.2023.2220027 -
Methods in Molecular Biology (Clifton,... 2024Morbilliviruses such as measles virus (MeV) are responsible for major morbidity and mortality worldwide, despite the availability of an effective vaccine and global...
Morbilliviruses such as measles virus (MeV) are responsible for major morbidity and mortality worldwide, despite the availability of an effective vaccine and global vaccination campaigns. MeV belongs to the mononegavirus order of viral pathogens that store their genetic information in non-segmented negative polarity RNA genomes. Genome replication and viral gene expression are carried out by a virus-encoded RNA-dependent RNA polymerase (RdRP) complex that has no immediate host cell analog. To better understand the organization and regulation of the viral RdRP and mechanistically characterize antiviral candidates, biochemical RdRP assays have been developed that employ purified recombinant polymerase complexes and synthetic RNA templates to monitor the initiation of RNA synthesis and RNA elongation in vitro. In this article, we will discuss strategies for the efficient expression and preparation of mononegavirus polymerase complexes, provide detailed protocols for the execution and optimization of RdRP assays, evaluate alternative options for the choice of template and detection system, and describe the application of the assay for the characterization of inhibitor candidates. Although MeV RdRP assays are the focus of this article, the general strategies and experimental approaches are readily transferable to related viruses in the mononegavirus order.
Topics: Measles virus; RNA-Dependent RNA Polymerase; Virus Replication; RNA, Viral; Mononegavirales; Animals; Viral Proteins; Humans
PubMed: 38743360
DOI: 10.1007/978-1-0716-3870-5_3 -
Journal of Clinical Microbiology Feb 2024Measles and rubella serological diagnoses are done by IgM detection. The World Health Organization Global Measles and Rubella Laboratory Network previously endorsed... (Meta-Analysis)
Meta-Analysis
Measles and rubella serological diagnoses are done by IgM detection. The World Health Organization Global Measles and Rubella Laboratory Network previously endorsed Siemens Enzygnost enzyme-linked immunosorbant assay kits, which have been discontinued. A recommended replacement has not been determined. We aimed to search for suitable replacements by conducting a systematic review and meta-analysis of IgM detection methods that are currently available for measles and rubella. A systematic literature search was performed in Medline, Embase, Global Health, Cochrane Central, and Scopus on March 22 and on 27 September 2023. Studies reporting measles and/or rubella IgM detection with terms around diagnostic accuracy were included. Risk of bias was assessed using QUADAS tools. Meta-DiSc and R were used for statistical analysis. Clinical samples totalling 5,579 from 28 index tests were included in the measles meta-analysis. Sensitivity and specificity of the individual measles studies ranged from 0.50 to 1.00 and 0.53 to 1.00, respectively. Pooled sensitivity and specificity of all measles IgM detection methods were 0.94 (CI: 0.90-0.97) and 0.94 (CI: 0.91-0.97), respectively. Clinical samples totalling 4,983 from 15 index tests were included in the rubella meta-analysis. Sensitivity and specificity of the individual rubella studies ranged from 0.78 to 1.00 and 0.52 to 1.00, respectively. Pooled sensitivity and specificity of all rubella IgM detection methods were 0.97 (CI: 0.93-0.98) and 0.96 (CI: 0.93-0.98), respectively. Although more studies would be ideal, our results may provide valuable information when selecting IgM detection methods for measles and/or rubella.
Topics: Humans; Rubella virus; Antibodies, Viral; Immunoglobulin M; Measles; Rubella; Serologic Tests
PubMed: 38275299
DOI: 10.1128/jcm.01339-23