BACKGROUND: Herpes zoster (HZ), commonly known as \"shingles,\" may contribute to cognitive decline through mechanisms such as neuroinflammation or direct neuronal injury. However, evidence on the longitudinal association between HZ and cognitive decline is conflicting and whether the risk differs by APOE ε4-carrier status has not been studied; prospective cohort studies on the association between HZ vaccination and cognitive decline are also lacking.
METHODS: We included 149,327 participants from three large cohorts-the Nurses\' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS)-to prospectively examine the association between HZ and subsequent subjective cognitive decline (SCD). Poisson regression was used to estimate the multivariable-adjusted relative risk (MVRR) of a 3-unit increment in SCD score according to years since HZ compared with participants with no history of HZ.
RESULTS: Compared with individuals with no history of HZ, the MVRR (95% CI) of a 3-unit increment in SCD score was significantly and independently higher among individuals with a history of HZ, but the duration of time since HZ when the elevated risk of SCD was statistically significant differed among the cohorts. In NHS, HZ was associated with higher long-term risk of SCD; compared with individuals with no history of HZ, the MVRR (95% CI) of a 3-unit increment in SCD score was 1.14 (1.01, 1.32) for ≥ 13 years since HZ. In NHS II, HZ was associated with higher risk of SCD in both the short-term [MVRR 1.34 (1.18, 1.53) for 1-4 years] and long-term [MVRR 1.20 (1.08, 1.34) for ≥ 13 years since HZ]. In HPFS, an elevated risk of SCD was suggested across all time points. Among the subset of participants with information on APOE ε4, there was a suggestion that the association differed by APOE ε4 carrier status, but the results were not consistent between women and men. Among the subset of women with information on HZ vaccination, there was a suggestion that the long-term risk of SCD may be greater among women who were not vaccinated against HZ.
CONCLUSIONS: Data from three large independent cohorts of women and men showed that HZ was associated with higher long-term risk of SCD, and the risk may differ by APOE ε4-carrier status.

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UNASSIGNED: Herpes Zoster in humans is the result of varicella zoster virus (VZV) infection. Injecting rats with varicella zoster virus produces pain similar to herpes zoster \"shingles\" pain in humans. . In a previous study, orofacial pain was induced by injecting the whisker pad of male rats with VZV and the pain response increased after attenuating neurexin 3 (Nrxn3) expression in the central amygdala. Neurons descend from the central amygdala to the lateral parabrachial nucleus and orofacial pain signals ascend to the lateral parabrachial nucleus. GABAergic neurons within the central amygdala regulate pain by inhibiting activity within the lateral parabrachial nucleus. Attenuating Nrxn3 expression in the central amygdala increased GABA release in the lateral parabrachial nucleus suggesting Nrxn3 controls pain by regulating GABA release. Nrxn3 can also control synaptic connections between neurons, and we hypothesized that Nrxn3 knockdown in the central amygdala would reduce the number of GABAergic synaptic connections in the lateral parabrachial nucleus and increase VZV associated pain.
UNASSIGNED: To test this idea, the number of synaptic connections between GABAergic cells of the central amygdala and excitatory or dynorphin positive neurons within the lateral parabrachial nucleus were quantitated after infusion of a virus expressing synaptophysin. Synaptophysin is a synaptic vesicle protein that labels neuronal synaptic connections. These connections were measured in rats with and without whisker pad injection of VZV and knockdown of Nrxn3 within the central amygdala. Orofacial pain was measured using a place escape avoidance paradigm.
UNASSIGNED: GABAergic synaptic connections were reduced in the lateral parabrachial nucleus after Nrxn3 knockdown. Rats with a reduction in the number of connections had an increase in VZV associated orofacial pain. Immunostaining with the pain marker prodynorphin indicated that the reduction in GABAergic connections was primarily associated with prodynorphin positive neurons.
UNASSIGNED: The results suggest Nrxn3 reduces VZV associated orofacial pain, in part, by enhancing synaptic connections between GABA cells of the central amygdala and pain neurons within the lateral parabrachial nucleus.

OBJECTIVE: To examine the frequency of recurrences, risk factors, and long-term clinical outcomes in subjects with herpes zoster ophthalmicus (HZO).
METHODS: Retrospective cohort study.
METHODS: All subjects with acute HZO seen at a single center from 2006 to 2016 were included in the study. The primary outcome measure was eye disease recurrence. The secondary outcome measure was moderate vision loss (≤20/50).
RESULTS: A total of 869 patients with acute HZO were identified, with a median follow-up time of 6.3 years (interquartile range 3.7-8.9 years). In all, 551 recurrences were observed, and at least 1 recurrence was seen in 200 subjects (23.0%), with uveitis (34.8%) being the most common. The median time to first recurrence was 3.5 months. Predictors of disease recurrence included immunosuppression (P = .026), higher presenting intraocular pressure (P = .001), corneal involvement (P = .001), and uveitis (P < .001) on multivariate analysis. Topical steroids were initiated in the first month of presentation in 437 subjects, and recurrence was observed in 184 (42.1%) of these subjects. Following cessation of topical steroid treatment, recurrence occurred after a median of 1.4 months (90% within 7 months). Moderate vision loss (≤20/50) occurred in 15.5%, 28.6%, 31.4%, 50.0%, and 57.4% of eyes with 0, 1, 2, 3, and 4 or more recurrences.
CONCLUSIONS: Recurrence of HZO eye disease is common, with an increased risk of vision loss with more recurrences. These findings indicate the need for close monitoring for potential recurrences, especially after cessation of topical steroid treatment, and in individuals with identified risk factors for recurrence.

BACKGROUND: Celiac Disease (CD) is associated with increased susceptibility to certain bacterial and viral infections. Herpes zoster (HZ) is a viral infection that can be prevented by immunization. In the US, the vaccine is recommended for adults ≥ 50 or ≥ 19 with certain at-risk conditions, not including CD.
OBJECTIVE: We aimed to determine if adult patients aged < 50 or ≥ 50 years with CD had a higher risk of developing HZ.
METHODS: We designed a retrospective cohort study. CD was defined as patients with the ICD-10 code for CD and positive Celiac serology. Patients with negative serology and lacking CD ICD-10 codes served as controls. Patients who had HZ before CD diagnosis were excluded. We formed two sub-cohorts, those aged < 50 (cohort 1) and aged ≥ 50 years (cohort 2), and evaluated HZ infection at 10-year follow-up. To account for confounding variables, we performed 1:1 propensity score matching (PSM).
RESULTS: Following PSM, cohort 1 had 6,826 CD patients, and cohort 2 had 5,337 CD patients and respective matched controls. After ten years of follow-up, in cohort 1, 62 CD patients developed HZ versus 57 controls, RR: 1.09 (CI: 0.76-1.56, p-value = 0.64). In cohort 2, 200 CD patients developed HZ versus 159 controls, RR: 1.2 (CI: 1.02-1.54, p-value = 0.03).
CONCLUSIONS: There was no significant difference in the likelihood of getting HZ in CD patients < 50, although CD patients ≥ 50 had a modestly increased risk. Our findings do not support routine early vaccination for HZ in CD, and the vaccine should be offered at age 50.

Herpes zoster (HZ) is a painful rash which typically affects older adults. This is of concern in Asia-Pacific given its aging population. As HZ epidemiology and burden are evolving, this systematic literature review aimed to update the current understanding of HZ burden and associated costs for selected Asia-Pacific locales. MEDLINE and Embase were searched for English articles of HZ studies conducted in Australia, China, Hong Kong, Japan, Korea, New Zealand, Singapore, and Taiwan. Eligible outcomes included HZ incidence and prevalence, occurrence of HZ-related complications, healthcare resource utilization, costs, and HZ-associated quality of life outcomes. This paper focused on HZ data in the general adult population (N = 90 articles). Substantial HZ-related disease and economic burden were observed in these locales, consistent with global trends. These findings reinforce the increasing burden of HZ and need for preventive strategies, which may include raising awareness and encouraging timely vaccination.
Herpes zoster, also known as shingles, is a painful rash that usually resolves after a few weeks, although some people experience serious or long-lasting complications. Shingles is common, affecting around one in every three individuals in their lifetime, and older persons are more likely to have shingles. Given the aging population in the Asia-Pacific region, shingles represents an increasingly important health issue as the proportion of older people increases. Vaccination can help prevent shingles and avoid its complications. New data on the trends and burden of shingles in this region are regularly generated. Therefore, in this study, we looked at studies from selected countries published over the past twenty years to summarize the latest available information on: how many people experience shingles in selected Asia-Pacific areas, how these individuals and societies are affected, and the related costs. Consistent with previous research, this study observed an increasing trend in the number of persons with shingles and costs of managing it, especially in older adults. In populations that are aging, there is a need for ways to reduce the risk of shingles and to lessen its burden on the healthcare system and society. Our findings can help to inform current development of strategies to reduce the risk of shingles, including education (on the burden and risk of shingles) and encouraging uptake of preventive measures.

UNASSIGNED: The objective of this study was to estimate the annual incidence rates of herpes zoster (HZ) and postherpetic neuralgia (PHN) among individuals aged ≥19 years and the proportion who received HZ vaccination among those aged ≥50 years.
UNASSIGNED: This observational cohort study was conducted with administrative claims data from HealthVerity and included insured individuals across the US. Crude and US age- and sex-standardized incidence rates of HZ and PHN were calculated from 1 January 2019 to 31 May 2022 by calendar year in persons aged ≥19 years. Outcomes were defined as ≥1 ICD-10 diagnosis code for HZ or PHN. Analyses were stratified by age, sex, and immunocompromised status. Among those aged ≥50 years, the proportion who received 1 or 2 doses of recombinant zoster vaccine (Shingrix) or 1 dose of Zostavax was calculated.
UNASSIGNED: Standardized annual incidence rates from 2019 to 2021 were 542 to 685 per 100 000 person-years for HZ and 35 to 38 per 100 000 person-years for PHN. Rates were highest among females, older adults, and individuals who were immunocompromised. From 1 January 2019 to 31 May 2022, 4.3% and 9.0% of persons aged ≥50 years received 1 and 2 doses of Shingrix, respectively, and 0.2% received 1 dose of Zostavax.
UNASSIGNED: In this US claims database analysis, HZ and PHN were more frequent among older adults, females, and individuals who were immunocompromised. Between 1 January 2019 and 31 May 2022, 9% of persons aged ≥50 years received 2 doses of the Shingrix vaccine. Greater efforts are needed to increase vaccine uptake against HZ, especially for those at highest risk.

BACKGROUND: Previous studies have reported a decreased risk of dementia with herpes zoster vaccination. Given this background, this systematic review and meta-analysis aimed to investigate the association between herpes zoster vaccination and the risk of dementia.
METHODS: We searched five databases until November 2023 for case-control, cross-sectional, or cohort studies investigating the association of herpes zoster vaccination and dementia. Odds ratios and 95% confidence intervals (95% CIs) were pooled in the meta-analysis. Meta-regression, subgroup, and sensitivity analysis were also conducted.
RESULTS: We evaluated a total of five studies (one cross-sectional, one case-control, and four cohort studies) that included a total number of 103,615 patients who were vaccinated with herpes zoster vaccine. All the studies were of high quality, ranging from 7 to 9. Due to the high heterogeneity (I2 = 100%, p < .00001) observed in our study, a random effect model was used for the analysis. The pooled odds ratio was 0.84 (95% CI: 0.50, 1.43), p (overall effect) = .53), indicating that herpes zoster vaccination reduces the risk of dementia.
CONCLUSIONS: Herpes zoster vaccination is associated with a reduction of the risk of dementia. More epidemiological studies are needed to confirm the association.

BACKGROUND: Immunisation against herpes zoster is recommended for adults aged ≥ 50 years. Two vaccines, a live attenuated (ZVL, Zostavax®) and an adjuvant recombinant subunit (HZ/su, Shingrix®), are available in Australia. Immunisation guidelines are shifting their recommendations towards HZ/su because of higher efficacy in preventing herpes zoster and associated complications. However, there are limited post-marketing data comparing the safety profiles of these vaccines.
METHODS: Data from SmartVax, an active surveillance system for monitoring adverse events following immunisation (AEFIs) utilised by > 450 clinics throughout Australia, were analysed. Data from patients aged ≥ 50 years, who received ZVL or HZ/su, from 1 June 2021 to 31 May 2022, at clinics that utilised SmartVax were included. The proportion of records where patients who reported any, local, and systemic AEFIs after receiving ZVL or HZ/su were compared using multivariable logistic regression models.
RESULTS: Data from 10,392 immunisation records (n = 8341 ZVL; n = 2051 HZ/su) were included. The proportion of AEFIs reported was higher with HZ/su (41.9 % [any], 33.8 % [local], 25.2 % [systemic]) than with ZVL (8.7 % [any], 6.2 % [local], 3.5 % [systemic]). After controlling for demographic variables, HZ/su presented a 6-fold increase in the odds (OR 6.44; 95 %CI: 5.57-7.46) of a reported AEFI compared to ZVL. Only 59 (0.6 %) of vaccinations lead to medical attention being sought due to an AEFI.
CONCLUSIONS: While rates of AEFIs was higher with HZ/su than ZVL, most AEFIs were mild and did not require medical attention. Our findings support the change in vaccine recommendations and the use of HZ/su in immunisation programs.