Analysis of factors associated with varicella-zoster virus susceptibility among children 0-12 years old in Taiwan

OBJECTIVES: Varicella is a highly infectious disease caused by varicella-zoster virus (VZV). The aim of this study was to explore the geographical difference of VZV antibody seroprevalence among children in private vaccination areas in Taiwan, controlling for potential factors relating to varicella susceptibility. PATIENTS AND METHOD: A cross-sectional survey of the seroprevalence of VZV antibodies among children 0-12 years of age was conducted in Taiwan between August and December 2003. Sera of children visiting the outpatient unit of the participating hospitals around the island were collected. Six hundred and fifty-six parents among those of the 931 children studied agreed to answer the self-administered questionnaire regarding the possible factors associated with varicella susceptibility. IgG antibodies to VZV were measured using an enzyme-linked immunosorbent assay kit, Enzygnost anti VZV/IgG. RESULTS: The susceptibility was the highest at age 1 year, and then decreased as the age increased. Children living in southern and eastern Taiwan showed higher susceptibility to varicella than those living in northern area (odds ratio (OR) = 2.71 and 2.10, respectively). Prior history of varicella infection, varicella vaccination, and contact with cases remained to be associated with the susceptibility after multivariate analysis. CONCLUSIONS: Children who lived in tropical and rural regions and those who had no history of varicella infection, varicella vaccination, and contact with cases, might be more susceptible to varicella. Island-wide VZV seroprevalence surveillance is required to examine whether the geographical difference of susceptibility in Taiwan will become less significant or disappear after the mass varicella vaccination program initiated in 2004.     

Epidemiology of varicella zoster virus infection in Canada and the United Kingdom.

Many countries are currently studying the possibility of mass vaccination against varicella. The objective of this study was to provide a comprehensive picture of the pre-vaccine epidemiology of the varicella zoster virus (VZV) to aid in the design of immunization programs and to adequately measure the impact of vaccination. Population-based data including physician visit claims, sentinel surveillance and hospitalization data from Canada and the United Kingdom were analysed. The key epidemiological characteristics of varicella and zoster (age specific consultation rates, seasonality, force of infection, hospitalization rates and inpatient days) were compared. Results show that the overall epidemiology of varicella and zoster is remarkably similar between the two countries. The major difference being that, contrary to Canada, the epidemiology of varicella seems to be changing in the United Kingdom with an important decrease in the average age at infection that coincides with a significant increase in children attending preschool. Furthermore, differences exist in the seasonality between the United Kingdom and Canada, which seem to be primarily due to the school calendar. These results illustrate that school and preschool contact patterns play an important role in the dynamics of varicella. Finally, our results provide baseline estimates of varicella and zoster incidence and morbidity for VZV vaccine effectiveness and cost-effectiveness studies.     

Varicella zoster virus infection occurs at a relatively young age in the Netherlands

Introduction

To date, there is no universal varicella vaccination in the Netherlands. We studied the seroprevalence of varicella zoster virus (VZV) specific antibodies and determinants for seropositivity among participants of a serosurveillance study, conducted in 2006/2007 among Dutch inhabitants 0–79 years of age.

Materials and methods

Serological testing of 6386 blood samples for VZV was performed with a fluorescent bead-based multiplex immunoassay. Seroprevalence and geometric mean concentration (GMC) were weighted for age, sex, ethnicity, and urbanization rate to the total Dutch population. Determinants for VZV seropositivity were identified among children younger than 6 years of age using a logistic regression model.

Results

The overall seroprevalence of VZV specific antibodies in the Dutch population was 94.6% (95% CI: 93.2–96.0%). This seroprevalence increased rapidly with age: at 6 years of age, more than 95% were seropositive. Determinants associated with lower VZV seropositivity were: young age, first-generation non-Dutch ethnicity, and low frequency of attendance at a day care center or nursery school. The GMC increased with age and was lower for women than for men from the age of 20 years onwards.

Conclusions

This study confirmed that VZV infection occurs at a younger age in the Netherlands compared to other countries, which might explain the low disease burden due to varicella. Introduction of universal varicella vaccination is not a foregone conclusion in the Netherlands. Changes in migration and day care usage will influence the age-specific risk on varicella and should therefore be monitored. Further research might elucidate the sex differences in VZV specific GMC.     

Varicella: previously healthy children sometimes develop complications

Three healthy boys, 3.5, 5 and 1.5 years of age, were admitted to hospital with a severe bacterial skin infection, cerebellar ataxia, and pneumonia, respectively, one week after the onset of varicella. They recovered completely after treatment. Studies in Europe report complications from varicella in 2.5% of healthy children. Most of these are neurological complications and secondary bacterial infections of skin and soft tissue. Last year, a European consensus was published that recommended that all healthy children be vaccinated against chickenpox. In The Netherlands, routine varicella zoster virus (VZV) vaccination has not (yet) been implemented. We propose a new discussion on the possible inclusion of VZV vaccination in the national vaccination programme.     

The comparative sero-epidemiology of varicella zoster virus in 11 countries in the European region

The European sero-epidemiology network (ESEN2) aims to standardise serological surveillance of varicella zoster virus (VZV) in 11 participant countries. In each country, serum banks were collected between 1996 and 2003 and tested for VZV antibodies. Assay results were standardised so that international comparisons could be made. Age-specific forces of infection were calculated for three age groups (<5, 5-9 and >or=10 years of age) and used to estimate the base reproduction number (R(0)) and the herd immunity threshold (H). Most VZV infection occurred in childhood, but there was a wide variation in transmissibility, with R(0) ranging from 16.9 in the Netherlands to 3.3 in Italy. Herd immunity thresholds varied from 70% in Italy to 94% in the Netherlands. There are substantial differences in VZV sero-epidemiology within the European region, which will need to be taken into account in designing national policies regarding VZV vaccination.     

Assessment of varicella underreporting in Italy

We conducted a study to assess the degree of varicella underreporting in Italy, and its distribution by age group and geographical area. Underreporting in individuals from 6 months to 20 years of age was computed as the ratio between the varicella seroprevalence in 1996 and the 1996 lifetime cumulative incidence based on statutory notifications. The degree of underreporting at the national level was 7.7 (95% CI 7.4-7.9); underreporting was greater in older age groups and in southern Italy. Quantification of underreporting can contribute to better understanding of the burden of varicella and to evaluating the potential impact of mass vaccination.     

Varicella-zoster virus seroprevalence in nursery and day-care workers in Lyon (France)

OBJECTIVE: Varicella is a potential occupational hazard for susceptible individuals working in pediatric institutions because infected adults run a greater risk of severe or even fatal varicella and because the disease is so common in children and so contagious. The seroprevalence of varicella-zoster virus (VZV) was examined in a sample of day-care workers in Lyon (France) to determine whether a targeted vaccination policy was needed. METHODS: Two hundred forty-one sera were sampled and analysed with an Elisa test between March and May 2001. Histories of past VZV infection were collected via questionnaires documented either before or after consultation of medical records or other sources of information. RESULTS: The overall VZV seroprevalence was 99.6%. The positive predictive values of past varicella histories (documented or not) were>99% showing that a history of previous varicella in day-care workers was reliable. However, only 68 to 71% of these with serologically confirmed varicella reported a prior history of varicella. All subjects reporting a non-positive history of varicella were seropositive. CONCLUSIONS: Virtually all day-care workers enrolled in this study presented serological evidence of VZV so that sub-populations at risk for varicella infection for which VZV vaccination may be effective could not be identified. However, the VZV seroprevalence of the workers in pediatric institutions being presumably higher than that of the general adult population (94-96.3%), vaccination of susceptible young recruits before any exposure to the VZV, or even vaccination of students willing to work in a pediatric institution, may be positive.     

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.     

Seroepidemiology of varicella-zoster virus infection in Catalonia (Spain). Rationale for universal vaccination programmes

With the aim of designing a strategy for vaccination against varicella-zoster virus (VZV), the results of a seroepidemiological survey on VZV infection carried out in a sample of the population of Catalonia are presented. Representative samples from schoolchildren (30 schools) and adults (97 municipal areas) were obtained by random cluster sampling. In the study, 883 children and 1253 adults were included. Age, gender, place of birth, place of residence, educational level and occupation were investigated in the study subjects. An ELISA test was used to measure varicella antibodies. The prevalence of varicella antibodies increased with age, being 85% in the 5-9 years age group, 92% in the 10-14 years age group, 94% in the 15-34 years age group and almost 100% in people over 35. No association was found between sociodemographic variables studied and prevalence levels of antibodies. These results suggest that the best vaccination strategy in Catalonia would be to add a temporary vaccination programme of pre-adolescents at 12 years to routine vaccination at 15 months.     

Modelling the impact of vaccination on the epidemiology of varicella zoster virus in Australia

OBJECTIVE: To model the impact of universal varicella vaccination in Australia. METHODS: The results of an Australia-wide serosurvey for varicella zoster virus (VZV) immunity were used to parameterise realistic, age-structured deterministic models (RAS) developed by Brisson and colleagues. We examined the impact of a vaccination program for one-year-olds alone, and with a catch-up campaign for 11-year-olds, on the incidence of varicella and zoster, using Australia's population structure. Morbidity was then determined by calculating the number of hospital in-patient days. RESULTS: Infant vaccination is predicted to reduce the incidence of varicella. However, zoster incidence is expected to increase initially, assuming exposure to varicella boosts immunity to zoster. Accumulated morbidity from both varicella and zoster is predicted to remain above that expected without vaccination for the first 70 years of an infant program (assuming 90% coverage with boosting for 20 years). However, after 70 years the net health savings from vaccination are predicted to increase substantially. CONCLUSIONS AND IMPLICATIONS: Infant vaccination is expected to be a successful long-term commitment to reducing morbidity associated with VZV infection in Australia.     

国产和进口水痘疫苗免疫效果对比研究

[目的 ]　比较国产和进口水痘疫苗免疫效果 ,了解宝山区儿童水痘—带状疱疹病毒 (VZV)自然感染情况。　[方法 ]　随机选择 2 6 5名无水痘病史的 0～ 7岁儿童调查血清抗VZV -IgG阳性率 ;选择 84名 1～ 2岁VZV易感儿童随机分成两组 ,分别接种国产和进口水痘疫苗 ,免疫后 6周采血 ,用酶联免疫吸附试验检测抗VZV -IgG。　 [结果 ]　 1～ 7岁儿童抗VZV -IgG阳性率分别为 2 .0 0 %、11.11%、2 0 .0 0 %、17.6 5 %、30 .77%、40 .0 0 %、32 .14 % ;免前抗VZV -IgG阴性儿童 ,分别接种国产和进口水痘疫苗后 ,抗体阳转率分别为 90 .70 % ( 39/43)和 95 .12 % ( 39/41) ,两者差别无显著性 ;两种疫苗的抗VZV-IgG几何平均滴度倒数 (GMRT)分别为 2 0 4.848( 95 %CI190 .73～ 2 6 0 4.79)和 482 .6 9( 95 %CI93.30～ 2 497.5 ) ,进口疫苗GMRT略高于国产疫苗。　 [结论 ]　宝山区婴幼儿 6个月内部分存在VZV -IgG母体免疫 ,7个月后母体免疫消失 ;国产水痘疫苗免疫效果良好 ,本区 1～ 7岁儿童是易感人群 ,尤其是 1～ 4岁易感儿童适宜接种     

Modelling the impact of immunization on the epidemiology of varicella zoster virus

The objective of this study was to develop and apply a dynamic mathematical model of VZV transmission to predict the effect of different vaccination strategies on the age-specific incidence and outcome of infection. To do so a deterministic realistic age-structured model (RAS) was used which takes account of the increased potential for transmission within school aged groups. Various vaccine efficacy scenarios, vaccine coverages and vaccination strategies were investigated and a sensitivity analysis of varicella incidence predictions to important parameters was performed. The model predicts that the overall (natural and breakthrough) incidence and morbidity of varicella would likely be reduced by mass vaccination of 12-month-old children. Furthermore, adding a catch-up campaign in the first year for 1-11 year olds seems to be the most effective strategy to reduce both varicella incidence and morbidity (in the short and long term), though with the possible detrimental effect of increasing the incidence of zoster.     

Seroprevalence of Varicella-Zoster virus IgG antibodies in Swiss children during the first 16 months of age

QUESTION UNDER STUDY: To investigate the persistence of maternal IgG antibodies against Varicella-Zoster virus (VZV) in infants and young children. METHODS: Serum specimens of children aged 0-16 months who had been hospitalized in our institution between 1994 and 1999 were identified from our routine serum collection. Exclusion criteria were: preterm delivery (<37 gestational weeks); suspected varicella infection or presence of exanthema of unknown etiology at time of serum collection; transfusion of blood products during 6 months preceding serum collection; foreign born mother; and previous VZV immunization. Serotesting for IgG antibodies against VZV was performed by use of a commercially available ELISA kit. RESULTS: Two hundred and fifty three serum specimens from 240 patients were analyzed. Age distribution of patients at time of specimen collection was: 0-3 months: n=57; >3-6 months: n=47; >6-9 months: n=47; >9-12 months: n=48; >12-16 months: n=54. Seroprevalence rates for IgG antibodies against VZV in the different age groups were 90% (0-3 months), 38% (>3-6 months); 0% (>6-9 and >9-12 months); and 7% (>12-16 months). CONCLUSIONS: Our results demonstrate high levels of passively acquired humoral immunity against varicella in Swiss infants during the first 3 months of life. Beyond the first 3 months of life IgG antibodies against VZV are lacking in the majority of patients and between 6 and 12 months of age all specimens tested were negative. Beyond the first year of life antibodies against varicella were detected in four samples, probably due to previous VZV infection. In accordance with current recommendations, VZV vaccination should ideally be administered to children 9 months of age and older, although our data indicate that successful immunization may be possible at earlier age (6 months onwards) in certain circumstances.     

Exposure to varicella boosts immunity to herpes-zoster: implications for mass vaccination against chickenpox

We present data to confirm that exposure to varicella boosts immunity to herpes-zoster. We show that exposure to varicella is greater in adults living with children and that this exposure is highly protective against zoster (Incidence ratio=0.75, 95% CI, 0.63-0.89). The data is used to parameterise a mathematical model of varicella zoster virus (VZV) transmission that captures differences in exposure to varicella in adults living with and without children. Under the 'best-fit' model, exposure to varicella is estimated to boost cell-mediated immunity for an average of 20 years (95% CI, 7-41years). Mass varicella vaccination is expected to cause a major epidemic of herpes-zoster, affecting more than 50% of those aged 10-44 years at the introduction of vaccination.     

Use of hospitalization and pharmaceutical prescribing data to compare the prevaccination burden of varicella and herpes zoster in Australia

The aims of the study were to compare the burden of varicella and herpes zoster in Australia. No national surveillance exists for varicella or herpes zoster. We used hospital morbidity data from 1993-9 and pharmaceutical prescribing data from 1995-9. In the financial year 1998/99, there were 4718 hospitalizations for zoster compared to 1991 for varicella. For varicella the mean age of patients was 15 years compared to 69 years for zoster. The mean length of stay in hospital was 4.2 days for varicella and 12.7 days for zoster. Varicella accounted for 8396 (3726 with principal diagnosis varicella) bed days compared to 26 266 (5382 with principal diagnosis of zoster) for zoster. The in-hospital case-fatality rate was 0.4% for varicella and 1% for zoster. In 1999, 59 200 community-based cases of zoster were treated with antivirals. We estimate that 157 266 cases of zoster occurred in the community in 1999, a rate of 830 per 100 000 population. Herpes zoster has a higher burden of disease than varicella, and must be a component of disease surveillance in order to determine the full impact of vaccination on the epidemiology of varicella zoster virus (VZV).     

Seroprevalence of varicella-zoster virus in the German population

The present study was conducted to generate data on the epidemiology of varicella-zoster virus (VZV) infections in Germany as a basis for health economic evaluations of varicella vaccination strategies. The survey was designed as a cross-sectional, age-stratified study of the VZV seroprevalence in the German population. The status of immunity of 4602 individuals a aged 0 to >70 years was investigated by means of an indirect enzyme immunoassay and the fluorescent antibody to membrane assay. After waning of maternal antibodies over the period of 6-9 months seropositivity rates remained low by the end of the 1st year of life. By the age of 4-5 years 62.5% (95% CI; 56.0-68.5) of the pre-school children had already been infected with VZV and at the age of 10-11 years 94.2% (95% CI; 91.0-96.0) of children were positive for anti-VZV antibodies. Among the age-group of >40 years old, only few individuals were susceptible for VZV. The median antibody levels to VZV did not significantly decline with increasing age. In comparison with figures of previous studies the age-specific seroprevalence data presented here do not provide evidence for an upward shift in the age distribution of varicella in Germany. Since the majority of VZV infections occurs during the early childhood, the best option to reduce the circulation of wild-type VZV in the population would be the immunization of young children.     

Review of the United States universal varicella vaccination program: Herpes zoster incidence rates,cost-effectiveness,and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data

In a cooperative agreement starting January 1995, prior to the FDA's licensure of the varicella vaccine on March 17, the Centers for Disease Control and Prevention (CDC) funded the Los Angeles Department of Health Services’ Antelope Valley Varicella Active Surveillance Project (AV-VASP). Since only varicella case reports were gathered, baseline incidence data for herpes zoster (HZ) or shingles was lacking. Varicella case reports decreased 72%, from 2834 in 1995 to 836 in 2000 at which time approximately 50% of children under 10 years of age had been vaccinated. Starting in 2000, HZ surveillance was added to the project. By 2002, notable increases in HZ incidence rates were reported among both children and adults with a prior history of natural varicella. However, CDC authorities still claimed that no increase in HZ had occurred in any US surveillance site. The basic assumptions inherent to the varicella cost–benefit analysis ignored the significance of exogenous boosting caused by those shedding wild-type VZV. Also ignored was the morbidity associated with even rare serious events following varicella vaccination as well as the morbidity from increasing cases of HZ among adults. Vaccine efficacy declined below 80% in 2001. By 2006, because 20% of vaccinees were experiencing breakthrough varicella and vaccine-induced protection was waning, the CDC recommended a booster dose for children and, in 2007, a shingles vaccination was approved for adults aged 60 years and older. In the prelicensure era, 95% of adults experienced natural chickenpox (usually as children)—these cases were usually benign and resulted in long-term immunity. Varicella vaccination is less effective than the natural immunity that existed in prevaccine communities. Universal varicella vaccination has not proven to be cost-effective as increased HZ morbidity has disproportionately offset cost savings associated with reductions in varicella disease. Universal varicella vaccination has failed to provide long-term protection from VZV disease.     

Seroepidemiology of varicella zoster virus infection in Vojvodina,Serbia

The present cross-sectional serosurvey constitutes the first effort to describe the varicella zoster virus (VZV) seroepidemiology in Serbia. An age-stratified serum bank of 3570 residual samples collected between 2015 and 2016 in each of the seven districts of the Vojvodina Province was tested for IgG anti-VZV antibodies with an enzyme immunoassay. Results were standardised into common units according to the European Sero-Epidemiology Network (ESEN2) methodology. Univariable and multivariable analyses were used to examine the relationships between standardised anti-VZV positivity or logarithmically transformed antibody titres and demographic features of study subjects. Seropositivity (85% overall) increased with age, in parallel with geometric mean titres. By the time of school entry, 68% of children were immune. The slower subsequent acquisition of immunity leaves epidemiologically relevant proportions of adolescents (7%), young adults (6%) and especially females of reproductive age (6%) prone to more severe forms of varicella. In the ongoing pre-vaccine era, natural infection provides a high level of collective immunity, with the highest VZV transmission in children of preschool age. The detected gaps in VZV immunity of the Serbian population support the adoption of the official recommendations for varicella immunisation of non-immune adolescents and young adults, including non-pregnant women of childbearing age.Key words: Antibodies to varicella zoster virus (anti-VZV), chickenpox, ESEN2, Europe, seroprevalence, standardisation, vaccines and immunisation     

Cellular immune response of a varicella vaccine following simultaneous DTaP and VZV vaccination

BACKGROUND: Chickenpox and zoster are an important cause of morbidity among children and adults. The ability of a new, thermostable vaccine to induce varicella-zoster-virus (VZV)-specific humoral and cell mediated immunity when given simultaneously with diphtheria-tetanus-acellular pertussis vaccine (DTaP) as a booster dose in the second year of life was investigated. METHODS: A new, temperature stable varicella vaccine (OKA-strain, SB-Biologicals, Rixensart, Belgium) was given simultaneously with a booster dose of DTaP vaccine. VZV-specific humoral and cell-mediated immunity was studied in the first 27 out of 232 vaccinated children at 16-28 months of age, from blood samples drawn just before and six weeks after vaccination. VZV-specific antibody response, T-cell proliferation, cytokine production and expression of activation markers (CD25, HLADR) on T-cells were analyzed. RESULTS: Vaccination resulted in a significant rise of VZV-specific serum IgG titers and in a strong VZV-specific T-cell response in all vaccinated infants. Analysis of the expression of activation marker revealed activation of both CD4+-T-helper- and CD8+-T-cells. CONCLUSIONS: The varicella vaccine given simultaneously with DTaP produced strong B- and T-cell responses alike. This is the first report to show that CMI to VZV is conferred to young children by vaccination with a temperature stable VZV vaccine.     

Seroepidemiology of varicella-zoster virus and reliability of varicella history in Turkish children, adolescents and adults

This study aimed to assess the age specific varicella-zoster virus (VZV) seroprevalence in Izmir, Turkey and to determine the reliability of a history of varicella to detect susceptible children, adolescents and adults. A questionnaire, including previous history of varicella, was completed for each participant and, in 590 of them, VZV-specific IgG was measured using an ELISA test. Overall, 28.5% of individuals were seronegative for VZV. By 5 years of age, only 25.5% of children were seropositive for VZV. Among adolescents and young adults, 18.8% and 11.7% were seronegative, respectively. The negative predictive value was 57.8%, decreasing with age (81.9% in children, 34.5% in adolescents and 8.3% in adults). In conclusion, a negative history of varicella is not a reliable predictor of varicella antibody status in adolescents and young adults. Serological testing before immunisation will be logical, rather than presumptive vaccination, for adolescents and adults with negative history of varicella.