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Arthritis Research & Therapy Jul 2023To compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea. (Comparative Study)
Comparative Study
BACKGROUND
To compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea.
METHODS
Using 2009-2019 Korea National Health Insurance Service database, we conducted a cohort study on RA patients initiating a JAKi or TNFi. The primary outcomes were herpes zoster (HZ), serious bacterial (SBI), and opportunistic infections (OI). Propensity-score fine-stratification (PSS) and weighting were applied to adjust for > 70 baseline covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing JAKi versus TNFi users.
RESULTS
We included 2963 JAKi initiators PSS-weighted on 5169 TNFi initiators. During a follow-up of 1.16 years, the most frequent type of infections was HZ with incidence rate (IR) per 100 person-years of 11.54 and 4.88 in JAKi and TNFi users, respectively. The IR of SBI was 1.39 and 1.32, respectively. The OI was rare with a majority being tuberculosis and showed an IR of 0.11 and 0.49 in JAKi and TNFi users, respectively. The PSS-weighted HR (95% CI) for individual types of infections was 2.37 (2.00-2.80) for HZ, 1.04 (0.71-1.52) for SBI, and 0.25 (0.09-0.73) for OI.
CONCLUSIONS
This population-based cohort study on RA patients treated with JAKi or TNFi in Korea showed an exceptionally high IR of HZ in both treatment groups compared to that from Western countries, with an approximately doubled risk associated with JAKi versus TNFi use. The risk of SBI was comparable, but the risk of OI, particularly tuberculosis, was less among JAKi than TNFi initiators.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Cohort Studies; Herpes Zoster; Herpesvirus 3, Human; Janus Kinase Inhibitors; Opportunistic Infections; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 37495973
DOI: 10.1186/s13075-023-03111-w -
Human Vaccines & Immunotherapeutics Dec 2023Herpes zoster (HZ) brings a significant economic burden. The HZ vaccine was introduced in China for the first time in 2020, and there is a lack of up-to-date information...
Herpes zoster (HZ) brings a significant economic burden. The HZ vaccine was introduced in China for the first time in 2020, and there is a lack of up-to-date information on the hospitalization costs and characteristics prior to vaccination. This study aimed to describe the characteristics and economic burden of HZ inpatients in Hunan Province, China, and analyze the factors influencing the length of stay (LOS) and costs. This was a retrospective study and we extracted information from the Chinese National Health Statistics Network Reporting System on HZ inpatients in Hunan Province, China from 2017 to 2019. Spatial join tools and Global or Local Moran's Index were used for the geographic analysis of hospitalized HZ incidence. Multivariate linear regression models were used to analyze the factors influencing LOS and costs. There were 44,311 HZ inpatients included in this study, incurring a total of $31,857,734 medical costs. These patients had a median LOS of 8 days and a median expenditure of $573.47. Older age, more comorbidities, and the presence of complications with nervous system involved were all significantly associated with longer LOS and higher costs. HZ infection resulted in a large direct medical cost and heavy disease burden, especially in patients with advanced age or underlying medical conditions. The HZ vaccine has the potential to effectively reduce the disease burden and should be widely popularized especially among high-risk groups.
Topics: Humans; Retrospective Studies; Financial Stress; Herpes Zoster; Herpesvirus 3, Human; Herpes Zoster Vaccine; Cost of Illness; Vaccination; Neuralgia, Postherpetic
PubMed: 37899682
DOI: 10.1080/21645515.2023.2268990 -
Viruses Jun 2023HSV-1 disease is a significant public health burden causing orofacial, genital, cornea, and brain infection. We previously reported that a trivalent HSV-2 gC2, gD2, gE2...
A Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Provides Outstanding Protection in Mice against Genital and Non-Genital HSV-1 Infection, Comparable to the Same Antigens Derived from HSV-1.
HSV-1 disease is a significant public health burden causing orofacial, genital, cornea, and brain infection. We previously reported that a trivalent HSV-2 gC2, gD2, gE2 nucleoside-modified mRNA-lipid nanoparticle (LNP) vaccine provides excellent protection against vaginal HSV-1 infection in mice. Here, we evaluated whether this HSV-2 gC2, gD2, gE2 vaccine is as effective as a similar HSV-1 mRNA LNP vaccine containing gC1, gD1, and gE1 in the murine lip and genital infection models. Mice were immunized twice with a total mRNA dose of 1 or 10 µg. The two vaccines produced comparable HSV-1 neutralizing antibody titers, and surprisingly, the HSV-2 vaccine stimulated more potent CD8 T-cell responses to gE1 peptides than the HSV-1 vaccine. Both vaccines provided complete protection from clinical disease in the lip model, while in the genital model, both vaccines prevented death and genital disease, but the HSV-1 vaccine reduced day two vaginal titers slightly better at the 1 µg dose. Both vaccines prevented HSV-1 DNA from reaching the trigeminal or dorsal root ganglia to a similar extent. We conclude that the trivalent HSV-2 mRNA vaccine provides outstanding protection against HSV-1 challenge at two sites and may serve as a universal prophylactic vaccine for HSV-1 and HSV-2.
Topics: Female; Animals; Mice; Herpesvirus 2, Human; Herpesvirus 1, Human; Herpes Genitalis; Nucleosides; Antibodies, Neutralizing; Viral Envelope Proteins; Antibodies, Viral; RNA, Messenger
PubMed: 37515169
DOI: 10.3390/v15071483 -
The Journal of Clinical Investigation Dec 2023Herpes zoster (HZ) is a substantial problem for people with decreased cell-mediated immunity, including older adults. The first vaccine approved for HZ prevention, the...
Herpes zoster (HZ) is a substantial problem for people with decreased cell-mediated immunity, including older adults. The first vaccine approved for HZ prevention, the zoster vaccine live (ZVL), which provided limited and short-lived protection, has been supplanted by the superior recombinant zoster vaccine (RZV), which provides robust and durable protection. To understand the mechanisms underlying the differential immunologic characteristics of the 2 vaccines, we used T cell receptor β chain sequencing and peptide-MHC class II tetramer staining to analyze recombinant glycoprotein E-specific (gE-specific) CD4+ T cell clonotypes in RZV and ZVL recipients. Compared with ZVL, RZV expanded more gE-specific CD4+ clonotypes, with greater breadth and higher frequency of public clonotypes. RZV recruited a higher proportion of clonotypes from naive than from memory cells, while ZVL recruited equally from memory and naive compartments. Compared with memory-derived, naive-derived clonotypes were more likely to last 5 or more years after immunization. Moreover, the frequency of tetramer+ persistent clones correlated with the frequency of tetramer+ naive CD4+ prevaccination T cells. We conclude that the ability of RZV to recruit naive CD4+ T cells into the response may contribute to the durability of its effect. The abundance, breadth, and frequency of public clonotypes may further add to its protective effect.
Topics: Humans; Aged; Herpes Zoster Vaccine; CD4-Positive T-Lymphocytes; Herpes Zoster; Herpesvirus 3, Human; Vaccination; Vaccines, Synthetic
PubMed: 37788096
DOI: 10.1172/JCI172634 -
Viruses Nov 2023The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1,... (Review)
Review
The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1, responsible for oral herpes, and HSV-2, primarily causing genital herpes. Both types can lead to significant complications, including neurological issues. Conventional treatment, involving acyclovir and its derivatives, faces challenges due to drug resistance. This underscores the imperative for continual research and development of new drugs, with a particular emphasis on exploring the potential of natural antivirals. Flavonoids have demonstrated promise in combating various viruses, including those within the herpesvirus family. This review, delving into recent studies, reveals the intricate mechanisms by which flavonoids decode their antiviral capabilities against HSV. By disrupting key stages of the viral life cycle, such as attachment to host cells, entry, DNA replication, latency, and reactivation, flavonoids emerge as formidable contenders in the ongoing battle against HSV infections.
Topics: Humans; Animals; Antiviral Agents; Flavonoids; Herpes Simplex; Herpesvirus 1, Human; Life Cycle Stages
PubMed: 38140581
DOI: 10.3390/v15122340 -
Diagnostic Microbiology and Infectious... Jul 2023Multiplex PCR can utilize limited clinical material and is more cost-effective and expected to be used for the detection of Treponema pallidum, herpes simplex virus type...
Multiplex PCR can utilize limited clinical material and is more cost-effective and expected to be used for the detection of Treponema pallidum, herpes simplex virus type 1 and 2 (HSV-1,2). We established a multiplex TP-HSV1-HSV2 Polymerase Chain Reaction (multiplex PCR) targeting the conserved regions of the PolA gene of TP and the UL42 gene of HSV1 and HSV2 to test skin lesions of 115 patients suspected of having TP and HSV1/2 infections. The laboratory sensitivities for all 3 pathogens were 300 copies/mL. The overall clinical sensitivity and specificity in secretion samples for TP were 91.7% and 100%, for HSV1 100% and 98%, and for HSV2 89.7% and 100%, respectively. The method appears superior in patients suspected of early TP infection but negative for nontreponemal antibody testing, and the method is also useful for the differential diagnosis of new skin lesions on genital, perianal, and oral sites of patients with a history of previous syphilis.
Topics: Humans; Herpesvirus 1, Human; Herpesvirus 2, Human; Treponema pallidum; Multiplex Polymerase Chain Reaction; Syphilis; Sensitivity and Specificity
PubMed: 37172529
DOI: 10.1016/j.diagmicrobio.2023.115958 -
Human Vaccines & Immunotherapeutics Dec 2023Individuals who are immunocompromised (IC) due to therapy or underlying disease are at increased risk of herpes zoster (HZ). This study evaluates the public health...
Individuals who are immunocompromised (IC) due to therapy or underlying disease are at increased risk of herpes zoster (HZ). This study evaluates the public health impact of recombinant zoster vaccine (RZV) relative to no HZ vaccination for the prevention of HZ among adults aged ≥18 years diagnosed with selected cancers in the United States (US). A static Markov model was used to simulate three cohorts of individuals who are IC with cancer (time horizon of 30 years; one-year cycle length): hematopoietic stem cell transplant (HSCT) recipients, patients with breast cancer (BC; a solid tumor example), and patients with Hodgkin's lymphoma (HL; a hematological malignancy example). Cohort sizes reflect the estimated annual incidence of each condition in the US population (19,671 HSCT recipients, 279,100 patients with BC, and 8,480 patients with HL). Vaccination with RZV resulted in 2,297; 38,068; and 848 fewer HZ cases for HSCT recipients, patients with BC, and patients with HL, respectively (each versus no vaccine). Vaccination with RZV also resulted in 422; 3,184; and 93 fewer postherpetic neuralgia cases for HSCT, BC, and HL, respectively. Analyses estimated the quality-adjusted life years gained to be 109, 506, and 17 for HSCT, BC, and HL, respectively. To prevent one HZ case, the number needed to vaccinate was 9, 8, and 10, for HSCT, BC, and HL, respectively. These results suggest RZV vaccination may be an effective option to significantly reduce HZ disease burden among patients diagnosed with selected cancers in the US.
Topics: Humans; Adult; United States; Adolescent; Female; Herpes Zoster Vaccine; Public Health; Cost-Benefit Analysis; Herpes Zoster; Herpesvirus 3, Human; Neuralgia, Postherpetic; Vaccines, Synthetic; Breast Neoplasms
PubMed: 36880669
DOI: 10.1080/21645515.2023.2167907 -
International Journal of Molecular... Jul 2023The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of...
The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of MSCs, which can also affect the regenerative potential and immunological status of tissues. It is not known whether human herpes simplex viruses 1 and 2 (HSV1 and HSV2), well-known human pathogens that can cause lifelong infections, can induce changes in MSCs. In non-healing ulcers, HSV infection is known to affect deeper tissue layers. In addition, HSV infection can recur after initially successful cell therapies. Our aim was to study the response of adipose-derived MSCs (ADMSCs) to HSV infection in vitro. After confirming the phenotype and differentiation capacity of the isolated cells, we infected the cells in vitro with HSV1-KOS, HSV1-532 and HSV2 virus strains. Twenty-four hours after infection, we examined the gene expression of the cells via RNA-seq and RT-PCR; detected secreted cytokines via protein array; and determined autophagy via Western blot, transmission electron microscopy (TEM) and fluorescence microscopy. Infection with different HSV strains resulted in different gene-expression patterns. In addition to the activation of pathways characteristic of viral infections, distinct non-immunological pathways (autophagy, tissue regeneration and differentiation) were also activated according to analyses with QIAGEN Ingenuity Pathway Analysis, Kyoto Encyclopedia of Genes and Genome and Genome Ontology Enrichment. Viral infections increased autophagy, as confirmed via TEM image analysis, and also increased levels of the microtubule-associated protein light chain 3 (LC3B) II protein. We identified significantly altered accumulation for 16 cytokines involved in tissue regeneration and inflammation. Our studies demonstrated that HSV infection can alter the viability and immunological status of ADMSCs, which may have implications for ADMSC-based cell therapies. Alterations in autophagy can affect numerous processes in MSCs, including the inhibition of tissue regeneration as well as pathological differentiation.
Topics: Humans; Herpesvirus 1, Human; Herpes Simplex; Mesenchymal Stem Cells; Herpesvirus 2, Human; Cytokines; Inflammation
PubMed: 37569367
DOI: 10.3390/ijms241511989 -
The Journal of Infectious Diseases Nov 2023Our study aimed to determine the risk of herpes zoster reactivation and coronavirus disease 2019 (COVID-19) vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored...
BACKGROUND
Our study aimed to determine the risk of herpes zoster reactivation and coronavirus disease 2019 (COVID-19) vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19]).
METHODS
This retrospective study analyzed herpes zoster cases diagnosed between 26 February 2021 and 30 June 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed.
RESULTS
In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose adjusted odds ratio [aOR], 1.11; 95% confidence interval [CI], 1.06-1.15; second dose aOR, 1.17; 95% CI, 1.12-1.23). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR], 1.09; 95% CI, 1.02-1.16). BNT162b2 was associated with an increased risk at 18 days postvaccination (aHR, 1.65; 95% CI, 1.35-2.02) and second dose (aHR, 1.10; 95% CI, 1.02-1.19). However, the risk did not increase in both analyses of ChAdOx1 vaccination.
CONCLUSIONS
mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required.
Topics: Humans; Adenoviridae; Adenoviridae Infections; BNT162 Vaccine; Case-Control Studies; ChAdOx1 nCoV-19; COVID-19; COVID-19 Vaccines; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Retrospective Studies; Vaccination; Vaccines, Attenuated
PubMed: 37549237
DOI: 10.1093/infdis/jiad297 -
Journal of Clinical Virology : the... Aug 2023The recent mpox outbreak has highlighted the need to rapidly diagnose the causative agents of viral vesicular disease to inform treatment and control measures. Common...
BACKGROUND
The recent mpox outbreak has highlighted the need to rapidly diagnose the causative agents of viral vesicular disease to inform treatment and control measures. Common causes of vesicular disease include Monkeypox virus (MPXV), clades I and II, Herpes simplex viruses Type 1 and Type 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Varicella-zoster virus (VZV) and Enteroviruses (EVs). Here, we assessed a syndromic viral vesicular panel for rapid and simultaneous detection of these 7 targets in a single cartridge.
OBJECTIVE
The aim of this study was to evaluate the QIAStat-Dx ® viral vesicular (VV) panel and compare with laboratory developed tests (LDTs). Limit of detection, inter-run variability, cross-reactivity and specificity were assessed. Positive and negative percent agreement, and correlation between assays was determined using 124 clinical samples from multiple anatomical sites.
RESULTS
The overall concordance between the QIAstat and LDTs was 96%. Positive percent agreement was 82% for HHV-6, 89% for HSV-1 and 100% for MPXV, HSV-2, EV and VZV. Negative percent agreement was 100% for all targets assessed. There was no cross-reactivity with Vaccinia, Orf, Molluscum contagiosum viruses, and a pooled respiratory panel.
CONCLUSION
The QIAstat VV multi-target syndromic panel combine ease of use, rapid turnaround, good sensitivity and specificity for enhanced diagnosis, clinical care and public health responses.
Topics: Humans; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Herpesvirus 6, Human; Virus Diseases; Viruses; Monkeypox virus
PubMed: 37364498
DOI: 10.1016/j.jcv.2023.105525