Potential relationship between cytomegalovirus and immunosenescence: Evidence from observational studies.

Immunosenescence (IS) occurs as a natural outcome of ageing and may be described as a decline in immune system flexibility and adaptability to sufficiently respond to new, foreign antigens. Potential factors that may precipitate IS include persistent herpesvirus infections, such as cytomegalovirus (CMV). Here, we conducted a review of the literature evaluating the potential association between CMV and IS. Twenty-seven epidemiologic studies that included direct comparisons between CMV-seropositive and CMV-seronegative immunocompetent individuals were analysed. The majority of these studies (n = 20) were conducted in European populations. The strength of evidence supporting a relationship between CMV, and various IS-associated immunologic endpoints was assessed. T-cell population restructuring was the most prominently studied endpoint, described in 21 studies, most of which reported a relationship between CMV and reduced CD4:CD8 T-cell ratio or modified CD8+ T-cell levels. Telomere length (n = 4) and inflammageing (n = 3) were less frequently described in the primary literature, and the association of these endpoints with CMV and IS was less pronounced. An emergent trend from our review is the potential effect modification of the CMV-IS relationship with both sex and age, indicating the importance of considering various effector variables when evaluating associations between CMV and IS. Our analysis revealed plausible mechanisms that may underlie the larger epidemiologic trends seen in the literature that support the indirect effect of CMV on IS. Future studies are needed to clarify CMV-associated and IS-associated immunologic endpoints, as well as in more diverse global and immunocompromised populations.

Estimated cytomegalovirus seroprevalence in the general population of the United States and Canada.

Seroprevalence data for cytomegalovirus (CMV), a widespread virus causing lifelong infection, vary widely, and contemporary data from the United States (US) and Canada are limited. Utilizing a modeling approach based on a literature review (conducted August, 2022) of data published since 2005, we determine age-, sex-, and country-specific CMV seroprevalence in the general US and Canadian populations. Sex-specific data were extracted by age categories, and a random-effects meta-regression model was used to fit the reported data (incorporating splines for the US). Seven studies reported US CMV seroprevalence (both sexes, aged 1‒89 years); all used National Health and Nutrition Examination Survey data. Due to limited population-based studies, Canadian estimates were modeled using other limited country data. In both countries, modeled seroprevalence estimates increased with age and were higher in females versus males (US: 49.0% vs. 41.6% at 18‒19 years; 61.5% vs. 50.0% at 38‒39 years; Canada: 23.7% vs. 13.7% at 18‒19 years; 32.6% vs. 22.6% at 38‒39 years). Notably, by young adulthood, one-half of US and one-quarter of Canadian females have acquired CMV. The observed differences in CMV seroprevalence in the US and Canada may partially reflect variations in general population characteristics.

Testing for Cytomegalovirus Among Individuals Who Were Immunocompromised, 2018-2022.

This cohort study investigates rates of cytomegalovirus testing before and during the COVID-19 pandemic among individuals who were immunocompromised.

A Qualitative Assessment of Clinical Practice Guidelines and Patterns for Congenital Cytomegalovirus in the United States.

Cytomegalovirus (CMV) infection during pregnancy may result in long-term health problems for children with congenital CMV (cCMV). Currently, no prevention or treatment interventions are approved by the Food and Drug Administration for a cCMV indication. Healthcare provider and public awareness is low, and formal clinical practice guidelines and local practice patterns vary. A pilot study of eight cCMV experts was performed using qualitative semi-structured interviews to better understand clinical practice guidelines and patterns in the United States. Results from participant interviews highlighted the need for better prenatal diagnostic techniques, broader neonatal screening opportunities, and more robust evidence supporting intervention strategies. Healthcare provider and public partnerships are essential for advancing cCMV guidelines and improving care delivery. Our results provide a preliminary knowledge base and framework for developing a consensus cCMV research agenda to address evidence gaps that limit the revision of clinical practice guidelines. The changes in clinical practice patterns that may arise as a result of further research have the potential to reduce risk during pregnancy and improve care for children with cCMV infection.

A systematic literature review of the economic and healthcare resource burden of cytomegalovirus.

OBJECTIVE: Cytomegalovirus (CMV) can infect individuals at any age, including infants, who may contract it from infected mothers (congenital CMV [cCMV]). Whereas CMV infection is typically asymptomatic or causes mild illness in healthy individuals, infection can result in severe outcomes in immunocompromised individuals and in infants with cCMV. This systematic review aims to characterize the economic impact of CMV and cCMV infections. METHODS: Medline, Embase, and LILACS databases were searched for publications reporting the economic impact of cCMV and CMV infections across all age groups. Manuscripts published between 2010 and 2020 from Australia, Latin America, Canada, Europe, Israel, Japan, the United States, and global (international, worldwide) studies were included; congress materials were excluded. Outcomes of interest included cCMV- and CMV-attributable direct costs/charges, resource utilization, and indirect/societal costs. RESULTS: Of 751 records identified, 518 were excluded based on duplication, population, outcome, study design, or country. Overall, 55 articles were eligible for full-text review; 25 were further excluded due to population, outcome, study design, or congress abstract. Two publications were additionally identified, resulting in economic impact data compiled from 32 publications. Of these, 24 publications reported cost studies of cCMV or CMV, including evaluation of direct costs/charges, healthcare resource utilization, and indirect/societal costs, and 7 publications reported economic evaluations of interventions. The populations, methods and outcomes used across these studies varied widely. CONCLUSIONS: CMV and cCMV infections impose a considerable economic impact on different countries, populations, and outcomes. There are substantial evidence gaps where further research is warranted.

Comparison of Overall Sensitivity and Specificity across Different Newborn Screening Algorithms for Congenital Cytomegalovirus.

Screening newborns for congenital cytomegalovirus (cCMV) infection is critical for early detection and prompt diagnosis of related long-term consequences of infection, such as sensorineural hearing loss and neurodevelopmental delays. The objective of this study was to describe the validity of different newborn cCMV infection screening approaches and compare the expected number of cCMV cases detected across targeted and universal screening algorithms. The overall sensitivity (OSn) of targeted screening algorithms that required failure of auditory brain stem response and transient evoked otoacoustic emissions (TOAE; two-fail serial testing) or TOAE only (one-fail serial testing) before diagnostic CMV testing using saliva and urine PCR tests was 79% and 88%, respectively. The OSn for two-fail serial testing with diagnostic CMV testing using dried blood spot (DBS) was 75%. In contrast, OSn was 90% for universal screening (saliva and urine PCR tests) and 86% for universal screening with DBS testing alone. Overall, specificities were 100% across all algorithms. Universal screening using DBS testing and universal screening using saliva and urine testing can potentially detect 312 and 373 more cCMV cases per 100,000 live births, respectively, than two-fail serial testing. Overall, implementing universal cCMV newborn screening would improve cCMV detection, ultimately leading to better health outcomes.

A systematic literature review on the humanistic burden of cytomegalovirus.

OBJECTIVE: Cytomegalovirus (CMV) infection is typically asymptomatic in healthy individuals; however, certain populations are vulnerable to infection and may develop serious sequelae. CMV infection may also have a broad impact on humanistic outcomes, including patient health status and quality of life (QoL). We conducted a systematic literature review (SLR) to describe the global humanistic burden of CMV and congenital CMV (cCMV) infections across all age groups. METHODS: Medline, Embase, and LILACS were searched to identify studies on humanistic outcomes following CMV infection, including health status/QoL and any outcomes in domains such as auditory performance, cognitive ability, developmental status, intelligence, language, memory, mental health, motor performance, social communication, speech, and vocabulary. The SLR included articles published from 2000 to 2020 and focused geographically on Australia, Europe, Israel, Japan, Latin America, and North America. RESULTS: Sixty-three studies met the inclusion criteria. In general, individuals with symptomatic cCMV infection experience a greater burden of disease and more substantial impact on QoL versus those with asymptomatic cCMV infection. Children with hearing loss due to cCMV infection, both symptomatic and asymptomatic, showed improved auditory outcomes following cochlear implantation. Newborns, infants, and children with cCMV infections had worse cognitive outcomes in psychological development, sequential and simultaneous processing, phonological working memory, and attention control versus age-matched controls without cCMV infection. CMV infection was also associated with cognitive decline in elderly populations. CONCLUSIONS: CMV infection can have substantial, lifelong, heterogenous impacts on humanistic outcomes, including health status and QoL, which should be considered when developing and implementing treatment and prevention strategies.

A systematic literature review of the global seroprevalence of cytomegalovirus: possible implications for treatment, screening, and vaccine development.

BACKGROUND: Cytomegalovirus (CMV) is a common pathogen that affects individuals of all ages and establishes lifelong latency. Although CMV is typically asymptomatic in healthy individuals, infection during pregnancy or in immunocompromised individuals can cause severe disease. Currently, treatments are limited, with no prophylactic vaccine available. Knowledge of the current epidemiologic burden of CMV is necessary to understand the need for treatment and prevention. A systematic literature review (SLR) was conducted to describe the most recent epidemiologic burden of CMV globally. METHODS: Medline, Embase, and LILACS were searched to identify data on CMV prevalence, seroprevalence, shedding, and transmission rates. The SLR covered the time period of 2010-2020 and focused geographically on Australia, Europe, Israel, Japan, Latin America (LATAM), and North America. Studies were excluded if they were systematic or narrative reviews, abstracts, case series, letters, or correspondence. Studies with sample sizes < 100 were excluded to focus on studies with higher quality of data. RESULTS: Twenty-nine studies were included. Among adult men, CMV immunoglobulin G (IgG) seroprevalence ranged from 39.3% (France) to 48.0% (United States). Among women of reproductive age in Europe, Japan, LATAM, and North America, CMV IgG seroprevalence was 45.6-95.7%, 60.2%, 58.3-94.5%, and 24.6-81.0%, respectively. Seroprevalence increased with age and was lower in developed than developing countries, but data were limited. No studies of CMV immunoglobulin M (IgM) seroprevalence among men were identified. Among women of reproductive age, CMV IgM seroprevalence was heterogenous across Europe (1.0-4.6%), North America (2.3-4.5%), Japan (0.8%), and LATAM (0-0.7%). CMV seroprevalence correlated with race, ethnicity, socioeconomic status, and education level. CMV shedding ranged between 0% and 70.2% depending on age group. No findings on CMV transmission rates were identified. CONCLUSIONS: Certain populations and regions are at a substantially higher risk of CMV infection. The extensive epidemiologic burden of CMV calls for increased efforts in the research and development of vaccines and treatments. TRIAL REGISTRATION: N/A.

A systematic literature review of herpes zoster incidence worldwide.

We conducted a systematic review to characterize the incidence rate of herpes zoster (HZ) in the general population, specifically in individuals ≥50 years of age. A total of 69 publications were included in the review. We found a cumulative incidence of HZ ranging from 2.9-19.5 cases per 1,000 population and an incidence rate of HZ ranging from 5.23-10.9 cases per 1,000 person-years. The cumulative incidence (3.22-11.2 versus 2.44-8.0 cases per 1,000 population) and incidence rates (6.05-12.8 versus 4.30-8.5 cases per 1,000 person-years) were higher in females than males. Studies revealed a trend of increasing incidence of HZ with increasing age and over time. Variations in incidence estimates can be attributed to the various study designs, case ascertainments, age distributions of the population and year of the study. HZ is associated with a substantial disease burden and is expected to increase due to population aging.

The adjuvanted recombinant zoster vaccine is efficacious and safe in Asian adults ≥ 50 years of age: a sub-cohort analysis of the ZOE-50 and ZOE-70 randomized trials.

In two large clinical trials (ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]), two doses of the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy (VE) against herpes zoster (HZ) in adults ≥50 years of age (YOA). This post-hoc analysis assessed the VE against HZ and postherpetic neuralgia (PHN), in participants from Asian study sites enrolled in ZOE-50/70. Reactogenicity and safety were also assessed. Participants ≥50 YOA were randomized 1:1 to receive 2 doses of either RZV or placebo, 2 months apart. VE was evaluated for a median follow-up of 4 years post-vaccination overall and by age in the ZOE-50 Asian population ≥50 YOA and in the pooled ZOE-50/70 Asian population ≥70 YOA. Of the 2,729 participants included in the ZOE-50 Asian population ≥50 YOA, 3 RZV and 66 placebo recipients reported a confirmed HZ episode. Overall VE was 95.6% (95% confidence interval [CI]: 86.4-99.1) against HZ and 100% (95% CI: 35.44-100) against PHN. In the pooled ZOE-50/70 Asian population ≥70 YOA, 4 RZV and 75 placebo recipients out of the 2,723 participants reported a confirmed HZ episode. Overall VE was 94.7% (95% CI: 85.9-98.6) against HZ and 89.8% (95% CI: 28.39-99.77) against PHN. Pain and myalgia were the most frequent solicited local and general adverse events, respectively, in both populations. No safety concern was identified during the study periods. RZV is highly efficacious against HZ and PHN and has an acceptable safety profile in Asian populations ≥50 YOA, similar to what was observed in the general ZOE-50/70 populations.Trademark statement: Shingrix is a trademark owned by or licensed to the GSK group of companies.

Completion of the two-dose recombinant zoster vaccine series in adults 50 years and older.

BACKGROUND: In 2017, a new adjuvanted recombinant zoster vaccine (RZV) was recommended for adults ≥50 years as two-dose series 2-6 months apart. We evaluated two-dose RZV completion and factors associated with completion. METHODS: The study included Kaiser Permanente Southern California members ≥50 years who received an RZV dose during April-November 2018 and had continuous membership 12 months before to 9 months after the first RZV dose. Completion was defined as receipt of the second dose ≥4 weeks to 9 months after the first dose (allowing 3-month grace period). Characteristics including age, sex, race/ethnicity, Medicaid status, neighborhood level income and education, comorbidities, history of zoster, health care utilization before and after the first dose, receipt of influenza vaccine, vaccination month (supply shortage proxy), concomitant vaccine, medical center, and medically attended reactions, pain, or gout after the first dose were compared between completers and non-completers. Adjusted odds ratios and 95% confidence intervals for factors associated with completion were estimated by multivariable logistic regression. RESULTS: Among 31,120 first dose recipients, 67.2% completed the series within 9 months. In adjusted analyses, higher completion was associated with White compared with Black or Hispanic race/ethnicity, higher neighborhood income and education, no chronic pulmonary disease, diabetes, or dementia, more outpatient visits and fewer emergency department visits before or after the first dose, no hospitalizations after the first dose, receipt of influenza vaccine, receipt of the first dose in June-November rather than April-May 2018, and no concomitant vaccine with the first dose. Systemic reactions or pain after the first dose was not associated with completion. CONCLUSION: Completion of RZV series appears suboptimal in the early phase of implementation. Despite similar accessibility in a health care system, completion varied by race/ethnicity, socioeconomic status, health status, and care seeking behavior, suggesting areas to target for improvement.

A systematic literature review to assess the burden of herpes zoster disease in China.

INTRODUCTION: Herpes zoster (HZ) or shingles occurs as a result of reactivation after a primary infection with varicella zoster virus (chickenpox). The burden of HZ in older adults in China is not well understood. We conducted a systematic literature review to understand the burden of disease related to HZ, its complications, and associated costs in China. AREAS COVERED: Using publications retrieved from Chinese and English literature databases, we described incidence and prevalence of HZ, occurrence of HZ-related complications, and costs associated with HZ in mainland China, Taiwan, and Hong Kong. EXPERT OPINION: The data, although limited, indicate that the burden of disease due to HZ is substantial in China, with incidence rates that are comparable to the rest of the world. Recently, an adjuvanted recombinant HZ vaccine was approved for use in China. Disease prevention is likely to reduce the burden of disease, with potentially significant economic benefits. However, understanding the public health impact of vaccination in China will require extensive baseline information about incidence, complication rates, and associated costs. This review gives an overview of available research, but also reveals existing gaps. Well-designed observational studies are needed to quantify the total burden of disease and potential impact of prevention through vaccination.

PLAIN LANGUAGE SUMMARY What is the context? Although Herpes zoster (shingles) is a common disease of older age, the burden of disease in China is not well described. 32% of the Chinese population is aged 50 years and Older and this proportion is increasing. As a result of the ageing population, the public burden associated with shingles is expected to increase over time. What is new? We accessed published studies in the English and Chinese language literature to explore available information describing shingles in China. The incidence of shingles in Taiwan, Hong Kong and mainland China appears to be similar to other countries, although reliable population-based data are currently sparse in Hong Kong and mainland China. What is the impact? Data describing the disease burden due to shingles are currently heterogeneous throughout China. This review is a first step to determine those populations which could benefit most from shingles vaccination. Preventing shingles through vaccination could benefit the individual as well as provide potentially significant economic benefits for the individual, the employer and the economy.

Critical evaluation of FDA-approved respiratory multiplex assays for public health surveillance.

INTRODUCTION: Clinical management and identification of respiratory diseases has become more rapid and increasingly specific due to widespread use of PCR(polymerase chain reaction) multiplex technologies. Although significantly improving clinical diagnosis, multiplexed PCR assays could have a greater impact on local and global disease surveillance. The authors wish to propose methods of evaluating respiratory multiplex assays to maximize diagnostic yields specifically for surveillance efforts. Areas covered: The authors review multiplexed assays and critically assess what barriers have limited these assays for disease surveillance and how these barriers might be addressed. The manuscript focuses specifically on the case study of using multiplexed assays for surveillance of respiratory pathogens. The authors also provide a method of validation of specific surveillance measures. Expert commentary: Current commercially available respiratory multiplex PCR assays are widely used for clinical diagnosis; however, specific barriers have limited their use for surveillance. Key barriers include differences in testing phase requirements and diagnostic performance evaluation. In this work the authors clarify phase testing requirements and introduce unique diagnostic performance measures that simplify the use of these assays on a per target basis for disease surveillance.