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Clinical Infectious Diseases : An... Sep 2023Encephalitis is a devastating neurologic disease often complicated by prolonged neurologic deficits. Best practices for the management of adult patients include...
Encephalitis is a devastating neurologic disease often complicated by prolonged neurologic deficits. Best practices for the management of adult patients include universal testing for a core group of etiologies, including herpes simplex virus (HSV)-1, varicella zoster virus (VZV), enteroviruses, West Nile virus, and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody encephalitis. Empiric acyclovir therapy should be started at presentation and in selected cases continued until a second HSV-1 polymerase chain reaction test is negative. Acyclovir dose can be increased for VZV encephalitis. Supportive care is necessary for other viral etiologies. Patients in whom no cause for encephalitis is identified represent a particular challenge. Management includes repeat brain magnetic resonance imaging, imaging for occult malignancy, and empiric immunomodulatory treatment for autoimmune conditions. Next-generation sequencing (NGS) or brain biopsy should be considered. The rapid pace of discovery regarding autoimmune encephalitis and the development of advanced molecular tests such as NGS have improved diagnosis and outcomes. Research priorities include development of novel therapeutics.
Topics: Adult; Humans; Acyclovir; Herpesvirus 3, Human; Encephalitis; Brain; Nervous System Diseases; Herpesvirus 1, Human; Encephalitis, Herpes Simplex
PubMed: 37485952
DOI: 10.1093/cid/ciad306 -
Nature Sep 2023Messenger RNA (mRNA) vaccines are being used to combat the spread of COVID-19 (refs. ), but they still exhibit critical limitations caused by mRNA instability and...
Messenger RNA (mRNA) vaccines are being used to combat the spread of COVID-19 (refs. ), but they still exhibit critical limitations caused by mRNA instability and degradation, which are major obstacles for the storage, distribution and efficacy of the vaccine products. Increasing secondary structure lengthens mRNA half-life, which, together with optimal codons, improves protein expression. Therefore, a principled mRNA design algorithm must optimize both structural stability and codon usage. However, owing to synonymous codons, the mRNA design space is prohibitively large-for example, there are around 2.4 × 10 candidate mRNA sequences for the SARS-CoV-2 spike protein. This poses insurmountable computational challenges. Here we provide a simple and unexpected solution using the classical concept of lattice parsing in computational linguistics, where finding the optimal mRNA sequence is analogous to identifying the most likely sentence among similar-sounding alternatives. Our algorithm LinearDesign finds an optimal mRNA design for the spike protein in just 11 minutes, and can concurrently optimize stability and codon usage. LinearDesign substantially improves mRNA half-life and protein expression, and profoundly increases antibody titre by up to 128 times in mice compared to the codon-optimization benchmark on mRNA vaccines for COVID-19 and varicella-zoster virus. This result reveals the great potential of principled mRNA design and enables the exploration of previously unreachable but highly stable and efficient designs. Our work is a timely tool for vaccines and other mRNA-based medicines encoding therapeutic proteins such as monoclonal antibodies and anti-cancer drugs.
Topics: Animals; Humans; Mice; Algorithms; Codon; COVID-19; COVID-19 Vaccines; Half-Life; Herpesvirus 3, Human; mRNA Vaccines; RNA Stability; RNA, Messenger; SARS-CoV-2
PubMed: 37130545
DOI: 10.1038/s41586-023-06127-z -
Viruses Jul 2023Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of... (Review)
Review
Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles). The focus of this review is on the wide spectrum of the possible neurological manifestations of VZV reactivation. While the most frequent reactivation syndrome is herpes zoster, this may be followed by the serious and painful post-herpetic neuralgia (PHN) and by many other neurological conditions. Prominent among these conditions is a VZV vasculopathy, but the role of VZV in causing giant cell arteritis (GCA) is currently controversial. VZV reactivation can also cause segmental motor weakness, myelitis, cranial nerve syndromes, Guillain-Barre syndrome, meningoencephalitis, and zoster sine herpete, where a neurological syndrome occurs in the absence of the zoster rash. The field is complicated by the relatively few cases of neurological complications described and by the issue of causation when a neurological condition is not manifest at the same time as the zoster rash.
Topics: Humans; Herpesvirus 3, Human; Herpes Zoster; Chickenpox; Neuralgia, Postherpetic; Alphavirus; Exanthema
PubMed: 37632006
DOI: 10.3390/v15081663 -
Human Vaccines & Immunotherapeutics Dec 2023The objective of this study was to critically review the cost-effectiveness (CE) of the recombinant zoster vaccine (RZV) against herpes zoster (HZ). A literature review... (Review)
Review
The objective of this study was to critically review the cost-effectiveness (CE) of the recombinant zoster vaccine (RZV) against herpes zoster (HZ). A literature review was conducted in PubMed, Embase, and Cochrane between January 1, 2017, and February 28, 2022, and on select public healthcare agency websites to identify and collect data from CE studies comparing RZV to zoster vaccine live (ZVL) or to no vaccination. Study characteristics, inputs, and outputs were collected. The overall CE of RZV was assessed. RZV vaccination against HZ is cost-effective in 15 out of 18 studies included in the present review. Varying incremental cost-effectiveness ratios (ICERs) observed may be associated with different assumptions on the duration of protection of RZV, as well as different combinations of structural and disease-related study (model) inputs driving the estimation of ICERs.
Topics: Humans; Herpes Zoster Vaccine; Cost-Benefit Analysis; Herpes Zoster; Herpesvirus 3, Human; Vaccination; Vaccines, Synthetic; Neuralgia, Postherpetic
PubMed: 36916240
DOI: 10.1080/21645515.2023.2168952 -
Journal of Virology Aug 2023Feline herpesvirus type 1 (FHV-1) is an enveloped dsDNA virus belonging to the family and is considered one of the two primary viral etiological factors of feline upper...
Feline herpesvirus type 1 (FHV-1) is an enveloped dsDNA virus belonging to the family and is considered one of the two primary viral etiological factors of feline upper respiratory tract disease. In this study, we investigated the entry of FHV-1 into host cells using two models: the AK-D cell line and primary feline skin fibroblasts (FSFs). We employed confocal microscopy, siRNA silencing, and selective inhibitors of various entry pathways. Our observations revealed that the virus enters cells via pH and dynamin-dependent endocytosis, as the infection was significantly inhibited by NHCl, bafilomycin A1, dynasore, and mitmab. Additionally, genistein, nystatin, and filipin treatments, siRNA knock-down of caveolin-1, as well as FHV-1 and caveolin-1 colocalization suggest the involvement of caveolin-mediated endocytosis during the entry process. siRNA knock-down of clathrin heavy chain and analysis of virus particle colocalization with clathrin indicated that clathrin-mediated endocytosis also takes part in the primary cells. This is the first study to systematically examine FHV-1 entry into host cells, and for the first time, we describe FHV-1 replication in AK-D and FSFs. IMPORTANCE Feline herpesvirus 1 (FHV-1) is one of the most prevalent viruses in cats, causing feline viral rhinotracheitis, which is responsible for over half of viral upper respiratory diseases in cats and can lead to ocular lesions resulting in loss of sight. Although the available vaccine reduces the severity of the disease, it does not prevent infection or limit virus shedding. Despite the clinical relevance, the entry mechanisms of FHV-1 have not been thoroughly studied. Considering the limitations of commonly used models based on immortalized cells, we sought to verify our findings using primary feline skin fibroblasts, the natural target for infection in cats.
Topics: Animals; Cats; Cat Diseases; Caveolin 1; Clathrin; Endocytosis; Herpesviridae Infections; RNA, Small Interfering; Varicellovirus
PubMed: 37493545
DOI: 10.1128/jvi.00681-23 -
Human Vaccines & Immunotherapeutics Aug 2023This review aimed to estimate the disease burden of herpes zoster (HZ) in China and explore the application of the Grades of Recommendation, Assessment, Development, and... (Meta-Analysis)
Meta-Analysis Review
This review aimed to estimate the disease burden of herpes zoster (HZ) in China and explore the application of the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach in studies of disease burden. We searched for the literature of observational studies analyzing HZ incidence in populations of all ages in China. Meta-analysis models were constructed to calculate the pooled incidence of HZ and pooled risks of postherpetic neuralgia (PHN), HZ recurrence, and hospitalization. Subgroup analysis was performed according to gender, age, and quality assessment score. The quality of evidence for incidence was rated using the GRADE system. Twelve studies with a total of 25,928,408 participants were included in this review. The pooled incidence for all ages was 4.28/1000 person years (95% CI 1.22-7.35). It increased with the increasing in age especially for individuals aged ≥60 y, which was 11.69/1000 person years (95% CI 6.56-16.81). The pooled risks of PHN, recurrence, and hospitalization were 12.6% (95% CI 10.1-15.1), 9.7% (95% CI 3.2-16.2), and 6.0/100,000 population (95% CI 2.3-14.2), respectively. The quality of the evidence assessment of the pooled incidence by the GRADE for all ages was 'low'; however, it was 'moderate' for the ≥60 yold subgroup. HZ is a serious public health problem in China and is more significant in individuals older than 60 y. Therefore, an immunization strategy for the zoster vaccine should be considered. The evidence quality assessment by the GRADE approach indicated that we had more confidence in the estimation of aged population.
Topics: Humans; Incidence; Herpes Zoster; Herpesvirus 3, Human; Neuralgia, Postherpetic; Herpes Zoster Vaccine; China
PubMed: 37424092
DOI: 10.1080/21645515.2023.2228169 -
European Journal of Medical Research Aug 2023The reactivation of herpesviruses (HHV) in COVID-19 patients is evident in the literature. Several reports have been published regarding the reactivation of these... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The reactivation of herpesviruses (HHV) in COVID-19 patients is evident in the literature. Several reports have been published regarding the reactivation of these viruses (HSV, VZV, EBV, and CMV) among those who got COVID-19 vaccines. In this study, we aimed to review the current evidence to assess whether HHVs reactivation has any association with the prior administration of COVID-19 vaccines.
METHODS
A systematic search was conducted on 25 September 2022 in PubMed/MEDLINE, Web of Science, and EMBASE. We included all observational studies, case reports, and case series which reported the reactivation of human herpesviruses following administration of COVID-19 vaccines.
RESULTS
Our systematic search showed 80 articles that meet the eligibility criteria. Among the evaluated COVID-19 vaccines, most of the vaccines were mRNA based. Evidence from observational studies showed the possible relation between COVID-19 vaccine administration and VZV and HSV reactivation. The results of our proportion meta-analysis showed that the rate of VZV reactivation among those who received the COVID-19 vaccine was 14 persons per 1000 vaccinations (95% CI 2.97-32.80). Moreover, our meta-analysis for HSV reactivation showed the rate of 16 persons per 1000 vaccinations (95% CI 1.06-46.4). Furthermore, the evidence from case reports/series showed 149 cases of HHV reactivation. There were several vaccines that caused reactivation including BNT162b2 mRNA or Pfizer-BioNTech (n = 76), Oxford-AstraZeneca (n = 22), mRNA-1273 or Moderna (n = 17), Sinovac (n = 4), BBIBP-CorV or Sinopharm (n = 3), Covaxin (n = 3), Covishield (n = 3), and Johnson and Johnson (n = 1). Reactivated HHVs included varicella-zoster virus (VZV) (n = 114), cytomegalovirus (CMV) (n = 15), herpes simplex virus (HSV) (n = 14), Epstein-Barr virus (EBV) (n = 6), and HHV-6 (n = 2). Most cases reported their disease after the first dose of the vaccine. Many patients reported having comorbidities, of which hypertension, diabetes mellitus, dyslipidemia, chicken pox, and atrial fibrillation were common.
CONCLUSION
In conclusion, our study showed the possible association between COVID-19 vaccination and herpesvirus reactivation. The evidence for VZV and HSV was supported by observational studies. However, regarding other herpesviruses (EBV and CMV), further research especially from observational studies and clinical trials is required to elucidate the interaction between COVID-19 vaccination and their reactivation.
Topics: Humans; BNT162 Vaccine; ChAdOx1 nCoV-19; COVID-19; COVID-19 Vaccines; Cytomegalovirus; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Herpesviridae Infections; Herpesvirus 3, Human; Herpesvirus 4, Human; Simplexvirus; Vaccination; Viruses
PubMed: 37559096
DOI: 10.1186/s40001-023-01238-9 -
The Cochrane Database of Systematic... Oct 2023Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of... (Review)
Review
BACKGROUND
Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of the varicella episode, the virus can remain latent in the sensitive dorsal ganglia of the spine. Years later, with declining immunity, the varicella zoster virus (VZV) can reactivate and cause herpes zoster, an extremely painful condition that can last many weeks or months and significantly compromise the quality of life of the affected person. The natural process of ageing is associated with a reduction in cellular immunity, and this predisposes older adults to herpes zoster. Vaccination with an attenuated form of the VZV activates specific T-cell production avoiding viral reactivation. Two types of herpes zoster vaccines are currently available. One of them is the single-dose live attenuated zoster vaccine (LZV), which contains the same live attenuated virus used in the chickenpox vaccine, but it has over 14-fold more plaque-forming units of the attenuated virus per dose. The other is the recombinant zoster vaccine (RZV) which does not contain the live attenuated virus, but rather a small fraction of the virus that cannot replicate but can boost immunogenicity. The recommended schedule for the RZV is two doses two months apart. This is an update of a Cochrane Review first published in 2010, and updated in 2012, 2016, and 2019.
OBJECTIVES
To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults.
SEARCH METHODS
For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2022, Issue 10), MEDLINE (1948 to October 2022), Embase (2010 to October 2022), CINAHL (1981 to October 2022), LILACS (1982 to October 2022), and three trial registries.
SELECTION CRITERIA
We included studies involving healthy older adults (mean age 60 years or older). We included randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine (any dose and potency) versus any other type of intervention (e.g. varicella vaccine, antiviral medication), placebo, or no intervention (no vaccine). Outcomes were cumulative incidence of herpes zoster, adverse events (death, serious adverse events, systemic reactions, or local reaction occurring at any time after vaccination), and dropouts.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included two new studies involving 1736 participants in this update. The review now includes a total of 26 studies involving 90,259 healthy older adults with a mean age of 63.7 years. Only three studies assessed the cumulative incidence of herpes zoster in groups that received vaccines versus placebo. Most studies were conducted in high-income countries in Europe and North America and included healthy Caucasians (understood to be white participants) aged 60 years or over with no immunosuppressive comorbidities. Two studies were conducted in Japan and one study was conducted in the Republic of Korea. Sixteen studies used LZV. Ten studies tested an RZV. The overall certainty of the evidence was moderate, which indicates that the intervention probably works. Most data for the primary outcome (cumulative incidence of herpes zoster) and secondary outcomes (adverse events and dropouts) came from studies that had a low risk of bias and included a large number of participants. The cumulative incidence of herpes zoster at up to three years of follow-up was lower in participants who received the LZV (one dose subcutaneously) than in those who received placebo (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.43 to 0.56; risk difference (RD) 2%; number needed to treat for an additional beneficial outcome (NNTB) 50; moderate-certainty evidence) in the largest study, which included 38,546 participants. There were no differences between the vaccinated and placebo groups for serious adverse events (RR 1.08, 95% CI 0.95 to 1.21) or deaths (RR 1.01, 95% CI 0.92 to 1.11; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of one or more adverse events (RR 1.71, 95% CI 1.38 to 2.11; RD 23%; number needed to treat for an additional harmful outcome (NNTH) 4.3) and injection site adverse events (RR 3.73, 95% CI 1.93 to 7.21; RD 28%; NNTH 3.6; moderate-certainty evidence) of mild to moderate intensity. These data came from four studies with 6980 participants aged 60 years or older. Two studies (29,311 participants for safety evaluation and 22,022 participants for efficacy evaluation) compared RZV (two doses intramuscularly, two months apart) versus placebo. Participants who received the new vaccine had a lower cumulative incidence of herpes zoster at 3.2 years follow-up (RR 0.08, 95% CI 0.03 to 0.23; RD 3%; NNTB 33; moderate-certainty evidence), probably indicating a favourable profile of the intervention. There were no differences between the vaccinated and placebo groups in cumulative incidence of serious adverse events (RR 0.97, 95% CI 0.91 to 1.03) or deaths (RR 0.94, 95% CI 0.84 to 1.04; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of adverse events, any systemic symptom (RR 2.23, 95% CI 2.12 to 2.34; RD 33%; NNTH 3.0), and any local symptom (RR 6.89, 95% CI 6.37 to 7.45; RD 67%; NNTH 1.5). Although most participants reported that their symptoms were of mild to moderate intensity, the risk of dropouts (participants not returning for the second dose, two months after the first dose) was higher in the vaccine group than in the placebo group (RR 1.25, 95% CI 1.13 to 1.39; RD 1%; NNTH 100, moderate-certainty evidence). Only one study reported funding from a non-commercial source (a university research foundation). All other included studies received funding from pharmaceutical companies. We did not conduct subgroup and sensitivity analyses AUTHORS' CONCLUSIONS: LZV (single dose) and RZV (two doses) are probably effective in preventing shingles disease for at least three years. To date, there are no data to recommend revaccination after receiving the basic schedule for each type of vaccine. Both vaccines produce systemic and injection site adverse events of mild to moderate intensity. The conclusions did not change in relation to the previous version of the systematic review.
Topics: Humans; Aged; Middle Aged; Herpesvirus 3, Human; Herpes Zoster Vaccine; Chickenpox; Herpes Zoster; Vaccines, Attenuated
PubMed: 37781954
DOI: 10.1002/14651858.CD008858.pub5 -
Ugeskrift For Laeger Nov 2023This is a case report of a 3-year-old boy who presented with unilateral anterior uveitis and tonic pupil following varicella-zoster virus (VZV) Infection. The patient...
This is a case report of a 3-year-old boy who presented with unilateral anterior uveitis and tonic pupil following varicella-zoster virus (VZV) Infection. The patient had red and irritated eyes and photophobia. Ophthalmological findings included anterior uveitis and tonic pupil accompanied by reduced vision and accommodation. An MRI of the cerebrum was normal. To ease the symptoms the patient was prescribed photophobia glasses with correction of hyperopia. Tonic pupil due to VZV infection is a rare complication, but may have long-term consequences, why patients with eye-involving VZV infection need to be examined by an ophthalmologist.
Topics: Male; Humans; Child; Child, Preschool; Chickenpox; Tonic Pupil; Photophobia; Herpesvirus 3, Human; Uveitis, Anterior; Acute Disease
PubMed: 38018730
DOI: No ID Found -
Annals of Internal Medicine Feb 2024A 2-dose series of recombinant zoster vaccine (RZV) was 97% effective against herpes zoster (HZ) in a pivotal clinical trial.
BACKGROUND
A 2-dose series of recombinant zoster vaccine (RZV) was 97% effective against herpes zoster (HZ) in a pivotal clinical trial.
OBJECTIVE
To evaluate real-world effectiveness of RZV against HZ.
DESIGN
Prospective cohort study.
SETTING
Four health care systems in the Vaccine Safety Datalink.
PARTICIPANTS
Persons aged 50 years or older.
MEASUREMENTS
The outcome was incident HZ defined by a diagnosis with an antiviral prescription. Cox regression was used to estimate the hazard of HZ in vaccinated persons compared with unvaccinated persons, with adjustment for covariates. Vaccine effectiveness (VE) was calculated as 1 minus the adjusted hazard ratio and was estimated by time since the last RZV dose and by corticosteroid use.
RESULTS
The study included nearly 2.0 million persons who contributed 7.6 million person-years of follow-up. After adjustment, VE of 1 dose was 64% and VE of 2 doses was 76%. After 1 dose only, VE was 70% during the first year, 45% during the second year, 48% during the third year, and 52% after the third year. After 2 doses, VE was 79% during the first year, 75% during the second year, and 73% during the third and fourth years. Vaccine effectiveness was 65% in persons who received corticosteroids before vaccination and 77% in those who did not.
LIMITATION
Herpes zoster could not be identified as accurately in these observational data as in the previous clinical trials.
CONCLUSION
Two doses of RZV were highly effective, although less effective than in the previous clinical trials. Two-dose effectiveness waned very little during the 4 years of follow-up. However, 1-dose effectiveness waned substantially after 1 year, underscoring the importance of the second dose.
PRIMARY FUNDING SOURCE
Centers for Disease Control and Prevention.
Topics: Humans; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Prospective Studies; Vaccination; Vaccines, Synthetic; Middle Aged; Clinical Trials as Topic
PubMed: 38190712
DOI: 10.7326/M23-2023