Seasonal transmission dynamics of varicella in Japan: The role of temperature and school holidays.

In Japan, major and minor bimodal seasonal patterns of varicella have been observed. To investigate the underlying mechanisms of seasonality, we evaluated the effects of the school term and temperature on the incidence of varicella in Japan. We analyzed epidemiological, demographic and climate datasets of seven prefectures in Japan. We fitted a generalized linear model to the number of varicella notifications from 2000 to 2009 and quantified the transmission rates as well as the force of infection, by prefecture. To evaluate the effect of annual variation in temperature on the rate of transmission, we assumed a threshold temperature value. In northern Japan, which has large annual temperature variations, a bimodal pattern in the epidemic curve was observed, reflecting the large deviation in average weekly temperature from the threshold value. This bimodal pattern was diminished with southward prefectures, gradually shifting to a unimodal pattern in the epidemic curve, with little temperature deviation from the threshold. The transmission rate and force of infection, considering the school term and temperature deviation from the threshold, exhibited similar seasonal patterns, with a bimodal pattern in the north and a unimodal pattern in the south. Our findings suggest the existence of preferable temperatures for varicella transmission and an interactive effect of the school term and temperature. Investigating the potential impact of temperature elevation that could reshape the epidemic pattern of varicella to become unimodal, even in the northern part of Japan, is required.

Emerging and Re-emerging Infections in Children: COVID/ MIS-C, Zika, Ebola, Measles, Varicella, Pertussis ... Immunizations.

The role of the emergency provider lies at the forefront of recognition and treatment of novel and re-emerging infectious diseases in children. Familiarity with disease presentations that might be considered rare, such as vaccine-preventable and non-endemic illnesses, is essential in identifying and controlling outbreaks. As we have seen thus far in the novel coronavirus pandemic, susceptibility, severity, transmission, and disease presentation can all have unique patterns in children. Emergency providers also have the potential to play a public health role by using lessons learned from the phenomena of vaccine hesitancy and refusal.

Communicability of varicella before rash onset: a literature review.

Varicella poses an occupational risk and a nosocomial risk for susceptible healthcare personnel and patients, respectively. Patients with varicella are thought to be infectious from 1 to 2 days before rash onset until all lesions are crusted, typically 4-7 days after onset of rash. We searched Medline, Embase, Cochrane Library and CINAHL databases to assess evidence of varicella-zoster virus (VZV) transmission before varicella rash onset. Few articles (7) contributed epidemiologic evidence; no formal studies were found. Published articles reported infectiousness at variable intervals before rash onset, between <1 day to 4 days prior to rash, with 1-2 patients for each interval. Laboratory assessment of transmission before rash was also limited (10 articles). No culture-positive results were reported. VZV DNA was identified by PCR before rash onset in only one study however, PCR does not indicate infectivity of the virus. Based on available medical literature, VZV transmission before rash onset seems unlikely, although the possibility of pre-rash, respiratory transmission cannot be entirely ruled out.

Cost-effectiveness of varicella and herpes zoster vaccination in Sweden: An economic evaluation using a dynamic transmission model.

OBJECTIVES: Comprehensive cost-effectiveness analyses of introducing varicella and/or herpes zoster vaccination in the Swedish national vaccination programme. DESIGN: Cost-effectiveness analyses based on epidemiological results from a specifically developed transmission model. SETTING: National vaccination programme in Sweden, over an 85- or 20-year time horizon depending on the vaccination strategy. PARTICIPANTS: Hypothetical cohorts of people aged 12 months and 65-years at baseline. INTERVENTIONS: Four alternative vaccination strategies; 1, not to vaccinate; 2, varicella vaccination with one dose of the live attenuated vaccine at age 12 months and a second dose at age 18 months; 3, herpes zoster vaccination with one dose of the live attenuated vaccine at 65 years of age; and 4, both vaccine against varicella and herpes zoster with the before-mentioned strategies. MAIN OUTCOME MEASURES: Accumulated cost and quality-adjusted life years (QALY) for each strategy, and incremental cost-effectiveness ratios (ICER). RESULTS: It would be cost-effective to vaccinate against varicella (dominant), but not to vaccinate against herpes zoster (ICER of EUR 200,000), assuming a cost-effectiveness threshold of EUR 50,000 per QALY. The incremental analysis between varicella vaccination only and the combined programme results in a cost per gained QALY of almost EUR 1.6 million. CONCLUSIONS: The results from this study are central components for policy-relevant decision-making, and suggest that it was cost-effective to introduce varicella vaccination in Sweden, whereas herpes zoster vaccination with the live attenuated vaccine for the elderly was not cost-effective-the health effects of the latter vaccination cannot be considered reasonable in relation to its costs. Future observational and surveillance studies are needed to make reasonable predictions on how boosting affects the herpes zoster incidence in the population, and thus the cost-effectiveness of a vaccination programme against varicella. Also, the link between herpes zoster and sequelae need to be studied in more detail to include it suitably in health economic evaluations.

Health Impact and Cost-effectiveness Assessment for the Introduction of Universal Varicella Vaccination in Switzerland.

BACKGROUND: Varicella, caused by the varicella-zoster virus, is a highly contagious infectious disease with substantial health and economic burden to society. Universal varicella vaccination (UVV) is not yet recommended by the Swiss National Immunization Program, which instead recommends catch-up immunization for children, adolescents and adults 11-40 years of age who have no reliable history of varicella or are varicella-zoster virus-IgG seronegative. The objective of this study was to perform an assessment of health impact and cost-effectiveness comparing UVV with current practice and recommendations in Switzerland. METHODS: A dynamic transmission model for varicella was adapted to Switzerland comparing 2 base-case schedules (no infant vaccination and 10% coverage with infant vaccination) to 3 different UVV schedules using quadrivalent (varicella vaccine combined with measles-mumps-rubella) and standalone varicella vaccines administered at different ages. Modeled UVV coverage rates were based on current measles-mumps-rubella coverage of approximately 95% (first dose) and 90% (second dose). Direct medical costs and societal perspectives were considered, with cost and outcomes discounted and calculated over a 50-year time horizon. RESULTS: UVV would reduce the number of varicella cases by 88%-90%, hospitalizations by 62%-69% and deaths by 75%-77%. UVV would increase direct medical costs by Swiss Franc (CHF) 39-49 (US $43-54) per capita and costs from a societal perspective by CHF 32-40 (US $35-44). Incremental quality-adjusted life-years per capita increased by 0.0012-0.0014. Incremental cost-effectiveness ratios for the UVV schedules versus the base-case were CHF 31,194-35,403 (US $34,452-39,100) per quality-adjusted life-year from the direct medical cost perspective and CHF 25,245-29,552 (US $27,881-32,638) from the societal perspective. CONCLUSIONS: UVV appears highly effective and cost-effective when compared with current clinical practice and recommendations in Switzerland from both a direct medical costs perspective and societal perspective.

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.

Pox Parties for Grannies? Chickenpox, Exogenous Boosting, and Harmful Injustices.

Some societies tolerate or encourage high levels of chickenpox infection among children to reduce rates of shingles among older adults. This tradeoff is unethical. The varicella zoster virus (VZV) causes both chickenpox and shingles. After people recover from chickenpox, VZV remains in their nerve cells. If their immune systems become unable to suppress the virus, they develop shingles. According to the Exogenous Boosting Hypothesis (EBH), a person's ability to keep VZV suppressed can be 'boosted' through exposure to active chickenpox infections. We argue that even if this hypothesis were true, immunization policies that discourage routine childhood varicella vaccination in order to prevent shingles for other people are unethical. Such policies harm children and treat them as mere means for the benefit of others, and are inconsistent with how parents should treat their children and physicians should treat their patients. These policies also seem incompatible with institutional transparency.

[Revised multidisciplinary guidelines 'Varicella'; broader indication for post-exposure prophylaxis]. / Herziene multidisciplinaire richtlijn 'Varicella'.

Post-exposure prophylaxis (PEP) with varicella zoster immunoglobulins (VZIG) should be administered as soon as possible after exposure to the virus, but always within ten days; in the previous guidelines this was within 96 hours. In cases of perinatal exposure, PEP with VZIG should be administered to neonates if the mother develops clinical chickenpox between seven days before delivery and seven days after delivery; in the previous guidelines this was between five days before delivery and two days after delivery. A new chapter on the treatment of chickenpox has been added to the guidelines.

Characteristics of within-household varicella transmission events associated with school outbreaks in Shanghai, China, 2009-2018.

Transmission of varicella occurs frequently in schools and households. We investigated the characteristics of varicella cases derived from within-household transmission and the modes of varicella transmission between school and household settings in Shanghai, China, from 2009 to 2018. Within-household transmission occurred in 278 households, of which 134 transmission events were between children. Sixty-one household varicella transmission events may be attributed to isolation procedures for infected students during school outbreaks, and 7.6% of school outbreaks were caused by schoolchildren cases derived from within-household transmission. The frequency of 'school-household-school' transmission adds an additional layer of complexity to the control of school varicella outbreaks. Administration of varicella vaccine as post-exposure prophylaxis after exposure is considered to be an effective measure to control varicella spread within households and schools.

New approaches to controlling an outbreak of chickenpox in a large immigration detention setting in England: the role of serological testing and mathematical modelling.

Chickenpox is caused by varicella-zoster-virus (VZV) and is highly contagious. Immigration detention settings are a high-risk environment for primary VZV transmission, with large, rapidly-changing populations in close quarters, and higher susceptibility among non-UK-born individuals. During outbreaks, operational challenges occur in detention settings because of high-turnover and the potential need to implement population movement restriction for prolonged periods. Between December 2017 and February 2018, four cases of chickenpox were notified amongst 799 detainees in an immigration removal centre (IRC). Microbiological investigations included case confirmation by vesicular fluid polymerase chain reaction, and VZV serology for susceptibility testing. Control measures involved movement restrictions, isolation of cases, quarantining and cohorting of non-immune contacts and extending VZV immunity testing to the wider detainee population to support outbreak management. Immunity was tested for 301/532 (57%) detainees, of whom 24 (8%) were non-immune. The level of non-immunity was lower than expected based on the existing literature on VZV seroprevalence in detained populations in England. Serology results identified non-immune contacts who could be cohorted and, due to the lack of isolation capacity, allowed the placement of cases with immune detainees. The widespread immunity testing of all detainees was proving challenging to sustain because it required significant resources and was having a severe impact on operational capacity and the ability to maintain core business activities at the IRC. Therefore, mathematical modelling was used to assess the impact of scaling back mass immunity testing. Modelling demonstrated that interrupting testing posed a risk of one additional case compared to continuing with testing. As such, the decision was made to stop testing, and the outbreak was successfully controlled without excessive strain on resources. Operational challenges generated learning for future outbreaks, with implications for a local and national policy on IRC staff occupational health requirements, and proposed reception screening of detainees for VZV immunity.

Evaluation of impact of one dose varicella vaccine on the incidence of chickenpox in Argentina.

INTRODUCTION: Varicella, also known as chickenpox is one of the most common immunizable diseases. In 1998, the World Health Organization (WHO) recommended to incorporate this vaccine in the national immunization programs, which Argentina did in 2015. OBJECTIVES: To describe the behavior of the varicella time series for the 2005-2017 period, and to evaluate the impact of the vaccine in Argentina. METHODOLOGY: An ecological observational study was performed, using the varicella cases reported in the National Health Monitoring System, and the data of the National census as secondary data sources. A model based time series analysis of the notified varicella cases in Argentina was performed, using a Negative Binomial Mixed Model. For the verification of the vaccine impact, the 2005-2014 period was selected, and a prognosis for the following years was performed. Impact was evaluated by comparing the rates and confidence intervals between the predicted and observed values. RESULTS: Argentina reported 1,775,587 varicella cases for the 2005-2017 period. The series exhibited seasonality, and, a decreasing trend in the number of cases was observed in 2016 and 2017. A reduction of the incidence rate after the implementation of the vaccine was observed. The transmission risk decreased in the country after vaccine implementation. CONCLUSIONS: This study is the first concrete evidence of the varicella incidence decline after the implementation of a single dose application program in Argentina.

Cost-effectiveness analysis of universal varicella vaccination in Turkey using a dynamic transmission model.

BACKGROUND: In 2013, Turkey introduced one-dose universal varicella vaccination (UVV) at 12 months of age. Inclusion of a second dose is being considered. METHODS: We developed a dynamic transmission model to evaluate three vaccination strategies: single dose at 12 months (1D) or second dose at either 18 months (2D-short) or 6 years of age (2D-long). Costs and utilization were age-stratified and separated into inpatient and outpatient costs for varicella and herpes zoster (HZ). We ran the model including and excluding HZ-related costs and impact of exogenous boosting. RESULTS: Five years post-introduction of UVV (1D), the projected varicella incidence rate decreases from 1,674 cases pre-vaccine to 80 cases/100,000 person-years. By 25 years, varicella incidence equilibrates at 39, 12, and 16 cases/100,000 person-years for 1D, 2D-short, and 2D-long strategies, respectively, using a highly effective vaccine. With or without including exogenous boosting impact and/or HZ-related costs and health benefits, the 1D strategy is least costly, but 2-dose strategies are cost-effective considering a willingness-to-pay threshold equivalent to the gross domestic product. The model predicted a modest increase in HZ burden during the first 20-30 years, after which time HZ incidence equilibrates at a lower rate than pre-vaccine. CONCLUSIONS: Our findings support adding a second varicella vaccine dose in Turkey, as doing so is highly cost-effective across a wide range of assumptions regarding the burden associated with varicella and HZ disease.

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.

Disease Extinction Versus Persistence in Discrete-Time Epidemic Models.

We focus on discrete-time infectious disease models in populations that are governed by constant, geometric, Beverton-Holt or Ricker demographic equations, and give a method for computing the basic reproduction number, [Formula: see text]. When [Formula: see text] and the demographic population dynamics are asymptotically constant or under geometric growth (non-oscillatory), we prove global asymptotic stability of the disease-free equilibrium of the disease models. Under the same demographic assumption, when [Formula: see text], we prove uniform persistence of the disease. We apply our theoretical results to specific discrete-time epidemic models that are formulated for SEIR infections, cholera in humans and anthrax in animals. Our simulations show that a unique endemic equilibrium of each of the three specific disease models is asymptotically stable whenever [Formula: see text].

Descriptive epidemiology of varicella based on national surveillance data before and after the introduction of routine varicella vaccination with two doses in Japan, 2000-2017.

Routine childhood immunization using two doses of the varicella vaccine was introduced in Japan in October 2014. In this study, we analyzed the data extracted from national varicella surveillance, including pediatric sentinel surveillance from 2000 to 2017 and hospitalized varicella surveillance from the 38th week of 2014 to the 37th week of 2017. Compared with the 2000-2011 baseline data, the number of varicella cases per sentinel decreased substantially by 76.6% overall and by 88.2% among children aged 1-4 years in 2017. Of 997 hospitalized patients, we found a decreasing trend in the number of cases among children aged <5 years. We also found a decreasing trend in the number of cases with complications among children aged 1-4 years. Data on the self-reported transmission sites in 35.5% (354/997) of the hospitalized varicella patients showed that transmission of varicella zoster virus (VZV) occurred frequently in household, at school for young children, in the workplace for adults, and at hospital for all age groups. Data from 29.0% (289/997) of the hospitalized patients with a self-reported source of infection showed that transmission of VZV occurred from a patient with herpes zoster (HZ) in 30.4% (88/289) of cases. Our data demonstrate a substantial decrease in the number of varicella cases in young children following introduction of routine childhood vaccination program with two-dose varicella vaccination in Japan. These data highlight the unique aspects of transmission sites across age groups and the important role of HZ cases in disease circulation.

Effectiveness of post-exposure prophylaxis during varicella outbreaks among primary and middle school students in Shanghai: An analysis of three-year surveillance data.

OBJECTIVES: To evaluate the effectiveness of post-exposure prophylaxis conducted during varicella outbreaks among students in Shanghai. METHODS: Surveillance data were collected from September 1, 2013 to December 31, 2016 involving 3524 susceptible students in 109 primary and middle school classes where emergency vaccinations (EVs) had been administered. Students were divided into two groups according to their prior vaccination (PV) varicella vaccine status. A secondary attack rate was used to compare EV and non-EV groups using a chi-squared test. Stratification analyses were performed, adjusting for the EV administration date, the vaccination coverage rate, and the number of cases prior to the EV. RESULTS: The effectiveness rate was 92.2% (95% confidence interval (CI): 37.1-99.0%) when EV was applied within 3 days following the outbreak onset date, and 95.2% (95% CI: 79.9-98.8%) when vaccination coverage was ≥80% among students with PV. When students with PV received an EV for varicella within 3 days, the effectiveness rate was 100%. CONCLUSIONS: EV showed high protective effectiveness for varicella during outbreaks, especially if administered within 3 days of an outbreak and in conjunction with a high coverage rate.

[Ophthalmic zoster: an uncommon dermatosis in infants]. / Le zona ophtalmique: une dermatose exceptionnelle chez le nourrisson.

We here report the case of a 9-month infant, born to a mother with a history of varicella in the third trimester of pregnancy but with no history of atopy, admitted to the emergency room with painful, pruritic rash in the right hemiface that had been ongoing for 4 days. During physical examination, the infant appeared to be in pain, with multiple cluster of grouped vesicles on erythematous skin in the right hemiforehead, in the right side of the nose and in the right cheek associated with edema of the upper and lower eyelids, with difficulty opening eyes and purulent conjunctival secretions. The infant was afebrile and in a good general condition. Ophthalmologic examination using the slit-lamp and fundus examination were normal. Complete blood count was normal. The diagnosis of ophthalmic zoster was retained on the basis of the clinical appearance of the lesions. The infant was treated with intravenous Aciclovir for 10 days associated with symptomatic local antiseptic treatment. Patient's evolution was marked by the regression of vesicular lesions and of edema. Viral serologic test and rapid HIV test were negative. The particularity of our study is the occurrence of ophthalmic zoster in an immunocompetent infant, which is rare in children. We made three differential diagnoses which included Kaposi-Juliusberg syndrome, cutaneous infection due to herpes simplex virus and facial erysipelas.