Association of herpes zoster vaccination and cardiovascular risk in patients with diabetes: long-term insights from a retrospective cohort study

Objectives
Herpes zoster (HZ) infection is associated with a higher risk of major adverse cardiovascular events (MACE), including stroke and coronary artery disease (CAD). Patients with diabetes are at an increased risk of MACE, highlighting the importance of studying this population to assess the potential protective effects of HZ vaccination. This study aims to investigate the risk of MACE after HZ vaccination in patients with diabetes.

Design
Retrospective cohort study.

Setting
Community-based population in the USA.

Participants
Using the TriNetX database, the study included 4.9 million patients with diabetes from 2006 to 2022. It established two cohorts: 68 178 patients in the HZ vaccination (comprising any HZ vaccine, Shingrix or Zostavax) and 4 835 246 patients in the no HZ vaccination group. After excluding patients with a history of MACE, immune disease and complications of HZ prior to the index date, the study cohort was reduced to 45 960 patients. Propensity score matching, accounting for age, sex, race, socio-economic status and disease comorbidities, was conducted to minimise study bias.

Interventions
HZ vaccination.

Outcome measures
MACE outcomes are defined as the first occurrence of CAD or stroke. Comparative risk analysis was conducted using HRs.

Results
Post matching, the mean patient age was 63.5 years, with 49.2% females. The incidence rate of MACE was lower among vaccinated patients compared with unvaccinated individuals, with an HR of 0.76 (0.72–0.79). For secondary endpoints, the HRs were 0.73 (0.69–0.78) for CAD, 0.79 (0.74–0.84) for stroke and 0.54 (0.52–0.57) for all-cause mortality. These protective effects remained consistent across different age groups, sexes and diabetes types, supporting the potential benefit of HZ vaccination in reducing cardiovascular risk.

Conclusions
HZ vaccination is associated with a lower risk of MACE in patients with diabetes. Further prospective studies are critically needed to confirm this finding.

Leggi
Febbraio 2025

Herpes—Reply

In Reply We greatly appreciate the Letter from Dr Bachmeyer discussing the utility of the Tzanck smear for bedside diagnosis of HSV infection in response to our JAMA Insights article on genital herpes. Unfortunately, the Tzanck smear has low sensitivity even for trained clinicians, ranging from 51% to 79%, and it is unclear whether it adds diagnostic value to clinical assessment of lesion morphology. As such, it is not recommended in the US Centers for Disease Control and Prevention’s sexually transmitted infections treatment guidelines. Additionally, as noted by Bachmeyer, the Tzanck smear does not differentiate between HSV-1 and HSV-2, which is a critical piece of information for counseling of patients with genital herpes. When a patient presents with a lesion, we recommend obtaining a swab for virologic diagnosis with HSV DNA polymerase chain reaction as an accurate and type-specific diagnostic modality.

Leggi
Gennaio 2025

Herpes

To the Editor I read with great interest the recent JAMA Insights article on genital herpes. However, the authors did not mention the Tzanck smear test in the Diagnosis section. Indeed, this technique described in 1947 by Arnault Tzanck is a neglected, but rapid, reliable, and cost-effective bedside technique to establish the diagnosis of acantholytic dermatoses, such as herpes simplex virus (HSV) and varicella zoster virus infections. Gentle scraping of the base of vesiculobullous lesions (incised if intact or stripped of their crust if ulcerated) with a scalpel allows for cytologic spreading on a glass slide, air-drying, and quick Giemsa staining. Instant microscopic examination by a trained cytologist enables identification of acantholytic and multinucleated keratinocytes with typical nuclear inclusion bodies indicating diagnosis of HSV and varicella zoster virus infections in 80% to 90% of patients, respectively. However, a Tzanck smear cannot differentiate between HSV-1 and HSV-2 infections. Of note, this diagnostic test can be useful in other acantholytic dermatoses, such as pemphigus and genetic skin diseases, including Darier disease and Hailey-Hailey disease. In conclusion, the Tzanck smear test can provide an early diagnosis of mucocutaneous HSV infections and enable appropriate treatment in skilled hands. For inexperienced clinicians, artificial intelligence can be used to evaluate Tzanck smear findings with high accuracy.

Leggi
Gennaio 2025

Optimal timing of recombinant herpes zoster virus vaccination for a JAK inhibitor treatment in rheumatoid arthritis: a multicentre, open-label, randomised comparative study (STOP-HZ study): study protocol

Introduction
Janus kinase (JAK) inhibitors are an important therapeutic option in the treatment of rheumatoid arthritis, but increase the risk of developing herpes zoster. Although a dry recombinant zoster vaccine (RZV) that can be used under immunosuppressive conditions has recently been developed, its optimal use and appropriate timing in patients scheduled to start JAK inhibitors is still unclear. The present study is designed to clarify the appropriate timing of JAK inhibitor initiation to measure varicella zoster virus (VZV)-specific IgG titers and VZV-specific T cell response in patients with rheumatoid arthritis who start tofacitinib at the first RZV vaccination or at the second one.

Methods and analysis
STOP HZ (Effectiveness and S afe T y O f P rophylactic Recombinant H erpes Z oster Virus Vaccination for Rheumatoid Arthritis Patients with Tofacitinib Treatment) study is a multicentre, open-label, randomised, comparative study in patients with rheumatoid arthritis who are scheduled to start tofacitinib. This study enrols 60 study subjects in 12 sites. Enrolled subjects receive RZV two times on day 1 and week 8 and initiate tofacitinib 5 mg two times a day at the time of their first RZV (day 1, group A) or second RZV (week 8, group B) based on randomisation. The random assignment is performed centrally in a 1:1 ratio. Patients in Group B continue the same treatment until the start of tofacitinib treatment. Primary endpoint is VZV-specific IgG antibody titers at week 12 compared with those at baseline in each group. Secondary endpoints include comparison of VZV-specific IgG antibody between the groups, changes in disease activity of rheumatoid arthritis, VZV-specific T cell response and adverse events.

Ethics and dissemination
The study has been approved by the Certified Review Board of Keio (No. 2022008), and conforms to the Declaration of Helsinki and good clinical practice guidelines. Written informed consent is obtained from participants prior to enrolment. The results of this study are planned to be submitted for publishment in relevant peer-review journals.

Trial registration number
jRCTs031230329.

Leggi
Novembre 2024

Association of herpes simplex virus infection with hearing loss: a cross-sectional study using NHANES data from 2011 to 2012 and 2015 to 2016

Objectives
To investigate the relationship between herpes simplex virus (HSV) and hearing loss using comprehensive population-based research.

Design
This cross-sectional study utilised data from the National Health and Nutrition Examination Survey (NHANES) to examine the relationship between HSV (types 1 and 2) and hearing loss. The final sample comprised 4608 participants aged 20–49 years. Weighted multivariate regression, subgroup and sensitivity analyses were employed for statistical evaluations.

Setting
Utilising the NHANES data, this cross-sectional study provides insights into the American population aged 20–49 years.

Participants
The study includes 4608 participants from the NHANES 2011–2012 and 2015–2016 cycles, focusing on those with complete data on HSV infection and hearing assessment.

Interventions (exposure)
The study analyses the association between HSV (types 1 and 2) infection and hearing loss, using weighted multivariate regression for statistical evaluations.

Results
We observed an association between HSV-1 infection and an increased likelihood of hearing impairment (OR, 1.4 (95% CI 1.1 to 1.9)). A similar association was noted for those coinfected with HSV-1 and HSV-2 (OR, 1.6 (95% CI 1.1 to 2.3)). Similarly, higher grades of hearing loss and elevated pure-tone averages were more prevalent in these groups. Notably, the association between HSV-1 and hearing impairment was more pronounced in individuals aged 20–34 (OR, 2.1 (95% CI 1.4 to 3.3); P for interaction=0.020) and those with a body mass index (BMI) below 30 (OR, 1.8 (95% CI 1.1 to 2.8); P for interaction=0.028).

Conclusions
Our findings suggest an association between HSV-1 infection or coinfections with HSV-1 and HSV-2 and the presence of hearing impairment. The association appears particularly pronounced among younger individuals and those with a lower BMI. Further prospective research is needed to explore the causal impact of HSV on auditory function.

Leggi
Settembre 2024

Genital Herpes

This JAMA Insights examines the history, diagnosis, prevention, and stigma of genital herpes infection in the US and explores treatments such as suppressive therapy.

Leggi
Settembre 2024