Exploring the Seasonal Drivers of Varicella Zoster Virus Transmission and Reactivation.

Varicella zoster virus (VZV) is a herpesvirus that causes chickenpox and shingles. The biological mechanisms underpinning the multidecadal latency of VZV in the body and subsequent viral reactivation-which occurs in approximately 30% of individuals-are largely unknown. Because chickenpox and shingles are endemic worldwide, understanding the relationship between VZV transmission and reactivation is important for informing disease treatment and control. While chickenpox is a vaccine-preventable childhood disease with a rich legacy of research, shingles is not a notifiable disease in most countries. To date, population-level studies of shingles have had to rely on small-scale hospital or community-level data sets. Here, we examined chickenpox and shingles notifications from Thailand and found strong seasonal incidence in both diseases, with a 3-month lag between peak chickenpox transmission season and peak shingles reactivation. We tested and fitted 14 mathematical models examining the biological drivers of chickenpox and shingles over an 8-year period to estimate rates of VZV transmission, reactivation, and immunity-boosting, wherein reexposure to VZV boosts VZV-specific immunity to reinforce protection against shingles. The models suggested that the seasonal cycles of chickenpox and shingles have different underlying mechanisms, with ambient levels of ultraviolet radiation being correlated with shingles reactivation.

The influence of immune individuals in disease spread evaluated by cellular automaton and genetic algorithm.

BACKGROUND AND OBJECTIVE: One of the main goals of epidemiological studies is to build models capable of forecasting the prevalence of a contagious disease, in order to propose public health policies for combating its propagation. Here, the aim is to evaluate the influence of immune individuals in the processes of contagion and recovery from varicella. This influence is usually neglected. METHODS: An epidemic model based on probabilistic cellular automaton is introduced. By using a genetic algorithm, the values of three parameters of this model are determined from data of prevalence of varicella in Belgium and Italy, in a pre-vaccination period. RESULTS: This methodology can predict the varicella prevalence (with average relative error of 2%-4%) in these two European countries. Belgium data can be explained by ignoring the role of immune individuals in the infection propagation; however, Italy data can be explained by considering contagion exclusively mediated by immune individuals. CONCLUSIONS: The role of immune individuals should be accurately delineated in investigations on the dynamics of disease propagation. In addition, the proposed methodology can be adapted for evaluating, for instance, the role of asymptomatic carriers in the novel coronavirus spread.

Transmission of Vaccine-Strain Varicella-Zoster Virus: A Systematic Review.

CONTEXT: Live vaccines usually provide robust immunity but can transmit the vaccine virus. OBJECTIVE: To assess the characteristics of secondary transmission of the vaccine-strain varicella-zoster virus (Oka strain; vOka) on the basis of the published experience with use of live varicella and zoster vaccines. DATA SOURCES: Systematic review of Medline, Embase, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and Scopus databases for articles published through 2018. STUDY SELECTION: Articles that reported original data on vOka transmission from persons who received vaccines containing the live attenuated varicella-zoster virus. DATA EXTRACTION: We abstracted data to describe vOka transmission by index patient's immune status, type (varicella or herpes zoster) and severity of illness, and whether transmission was laboratory confirmed. RESULTS: Twenty articles were included. We identified 13 patients with vOka varicella after transmission from 11 immunocompetent varicella vaccine recipients. In all instances, the vaccine recipient had a rash: 6 varicella-like and 5 herpes zoster. Transmission occurred mostly to household contacts. One additional case was not considered direct transmission from a vaccine recipient, but the mechanism was uncertain. Transmission from vaccinated immunocompromised children also occurred only if the vaccine recipient developed a rash postvaccination. Secondary cases of varicella caused by vOka were mild. LIMITATIONS: It is likely that other vOka transmission cases remain unpublished. CONCLUSIONS: Healthy, vaccinated persons have minimal risk for transmitting vOka to contacts and only if a rash is present. Our findings support the existing recommendations for routine varicella vaccination and the guidance that persons with vaccine-related rash avoid contact with susceptible persons at high risk for severe varicella complications.

Myths and Misconceptions: Varicella-Zoster Virus Exposure, Infection Risks, Complications, and Treatments.

Varicella zoster and herpes zoster are infections caused by the highly contagious varicella-zoster virus (VZV). Despite widespread availability of vaccines against VZV, as well as varicella vaccination rates >95%, VZV remains a public health concern because of several common myths and misconceptions. Because of the success of routine varicella vaccination programs, some people mistakenly believe that varicella and herpes zoster are now no longer a threat to public health. Another common misconception is that shingles is less infectious than varicella; however, clinical evidence indicates otherwise. Several knowledge gaps exist around VZV transmission and the availability and use of varicella zoster immune globulin (human) for postexposure prophylaxis against VZV. To help reduce the incidence of severe disease in high-risk individuals (eg, elderly people, pregnant women, unvaccinated persons, infants, and immunocompromised children and adults), this article addresses misbeliefs and broadens awareness of VZV exposure, infection risks, complications, and treatments.

Nosocomial transmission of chickenpox and varicella zoster virus seroprevalence rate amongst healthcare workers in a teaching hospital in China.

BACKGROUND: Varicella zoster virus (VZV) is a highly contagious herpesvirus with potential for nosocomial transmission. However, the importance of nosocomial chickenpox outbreak in China has often been ignored. With the increasing immunocompromised population in China, a thorough review of issues related to nosocomial transmission and the seroprevalence rate of VZV among healthcare workers is necessary. METHODS: Retrospective case finding for nosocomial transmission of chickenpox was conducted between January 1, 2013 and December 31, 2017. Cases were identified based on clinical features compatible with chickenpox. A cross-sectional study on the seroprevalence rate of VZV among healthcare workers (HCWs) was conducted between January 1, 2014 and December 31, 2017. The serum VZV antibodies of 1804 HCWs were measured by enzyme-linked immunosorbent assay (ELISA). The seroprevalence rate of VZV antibodies, the positive predictive value and negative predictive value of self-reported history of varicella were analyzed. The economic impact associated with nosocomial transmission of VZV was also assessed. RESULTS: A total of 8 cases of chickenpox were identified in three nosocomial transmissions, including 4 HCWs who were infected nosocomially. The overall seroprevalence rate of VZV was 88.4%, which significantly increased with age (P < 0.01). The seroprevalence rates of HCWs with different genders and occupations showed no statistically significant differences. The positive and negative predictive values of a self-reported history of varicella were 80.8 and 10.6% respectively. An estimation of 163.3 person-days of work were lost in each nosocomial transmission and 86.7 infection control unit person-hours were required for each outbreak investigation. The cost of VZV IgG ELISA screening was estimated to be 83 USD per nosocomial transmission. CONCLUSIONS: Nosocomial transmission of VZV occurred repeatedly in the hospital setting. An alarming 11.6% of HCWs were seronegative for VZV, which might increase the risk of nosocomial infection and outbreak for other susceptible co-workers and patients. This is especially important in the setting of a teaching hospital where many immunocompromised patients were managed. Furthermore, the positive predictive value of self-reported varicella on seroprevalence rate in our study was lower than those reported in other countries, therefore serological testing of VZV antibodies with subsequent vaccination for all non-immune HCWs should be considered.

Varicella zoster virus transmission dynamics in Vojvodina, Serbia.

This study aimed at establishing baseline key epidemiological parameters for varicella zoster virus (VZV) infection in Vojvodina, Serbia, with the ultimate goal to quantify the VZV transmission potential in the population. Seroprevalence data generated during the first large cross-sectional VZV serosurvey were modelled, using a two-tiered modelling approach to calculate age-specific forces of infection (FOI), the basic reproduction number (R0) and herd immunity threshold (H). Seroprevalence and modelling data were compared with corresponding pre-vaccination epidemiological parameters from 11 countries participating in the European Sero-Epidemiology Network 2 (ESEN2) project. Serbia fits into the general dynamic VZV transmission patterns in Europe in the pre-vaccine era, with estimated R0 = 4.12, (95% CI: 2.69-7.07) and H = 0.76 (95% CI: 0.63-0.86). The highest VZV transmission occurs among preschool children, as evidenced by the estimation of the highest FOI (0.22, 95% CI: 0.11-0.34) in the 0.5-4 age group, with a peak FOI of 0.25 at 2.23 years. Seroprevalence was consistently lower in 5-14 year-olds, resulting in considerable shares of VZV-susceptible adolescents (7.3%), and young adults (6%), resembling the situation in a minority of European countries. The obtained key epidemiological parameters showed most intense VZV transmission in preschool children aged <4 years, justifying the consideration of universal childhood immunization in the future. National immunization strategy should consider programs for VZV serologic screening and immunization of susceptible groups, including adolescents and women of reproductive age. This work is an important milestone towards the evaluation of varicella immunization policy options in Serbia.

Managing varicella zoster virus contact and infection in patients on anti-rheumatic therapy.

Chickenpox and shingles can be more severe and occasionally life threatening in immunosuppressed patients. As such, some groups warrant a more detailed history, serological testing and consideration of prophylaxis following contact with the virus. Active disease may also require more aggressive treatment with antivirals. Guidance for the use of varicella zoster immunoglobulin has recently been updated by Public Health England with important implications for rheumatology patients.

Projections of zoster incidence in Australia based on demographic and transmission models of varicella-zoster virus infection.

Re-exposure to varicella infection is believed to delay the occurrence of herpes zoster (HZ), which has led to predictions of increased HZ following introduction of varicella vaccination programs. However, there is evidence of rising HZ rates before vaccination was introduced. Here, we explore a potential explanation for this effect through demographic change leading to reductions in varicella exposure and boosting in the context of Australia over the 20th century. To study this hypothesis, we integrated observed changes in Australian birth and age-specific death rates with a varicella transmission model. The model was then calibrated to age-specific pre-vaccination seroprevalence (1997-9) and hospitalization data (1993-2009). Model simulations predicted that declining birth rates led to a 50% reduction in varicella incidence over the 20th century. When combined with the impacts of an aging population, the simulations further suggested that HZ incidence should have increased by 50% over the 20th century. However, we found that after age-standardization, the residual increase in HZ due to reduced boosting was only about 8% over the 20th century. Results were also sensitive to the assumed duration of immunity to HZ and whether multiple HZ episodes were possible. Despite a strong predicted effect of demographic change on varicella incidence, our findings suggest that improved survival is the main contributor to any rise in HZ rates prior to vaccination in Australia. Removing survival effects through age-standardization is recommended when considering epidemiologic or model-based analysis of past trends in HZ.