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Special Article

Consensus: Varicella Vaccination of Healthy Children

A Challenge for Europe

Rentier, Bernard PhD, DSc*; Gershon, Anne A. MD the Members of the European Working Group on Varicella (EuroVar)

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The Pediatric Infectious Disease Journal: May 2004 - Volume 23 - Issue 5 - p 379-389
doi: 10.1097/01.inf.0000122606.88429.8f
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Abstract

Primary infection with varicella-zoster virus (VZV) results in varicella or chickenpox, a common and highly contagious childhood disease. VZV infection is generally perceived as a benign disease in children. However, it can be associated with wide-ranging complications, such as skin or soft tissue infections, pneumonia, central nervous system dysfunction and Reye’s syndrome, 1 and can occasionally be fatal. 2 Furthermore primary VZV infection in adults is associated with increased morbidity and mortality. 2

Following primary infection, VZV becomes latent, kept under control by cell-mediated immune mechanisms. Many years later the virus can reactivate, resulting in herpes zoster (HZ) or shingles, usually characterized by a painful rash. Complications include postherpetic neuralgia and several other neurologic sequelae, such as encephalitis, ventriculitis and motor nerve paresis. 3 However, varicella is a vaccine-preventable disease. A live attenuated varicella vaccine, based on the Oka VZV strain, was developed in the early 1970s. Currently the two most widely used vaccines are Varilrix (GlaxoSmithKline) and Varivax (Merck & Co.). A routine varicella vaccination program targeting healthy children has been implemented in the US, 4,5 but universal varicella vaccination has yet to be accepted in Europe. The data presented in this paper are principally from studies in the US.

In 1998 the US-based VZV Research Foundation (VZVRF) formed EuroVar, the European Working Group on Varicella, to study the epidemiology of varicella and explore the desirability and feasibility of universal varicella vaccination in Europe. The inaugural meeting of the group was held in December 1998 in Liège, Belgium. Subsequently the membership of EuroVar was expanded and further meetings were held in Liège (January 2000), Berlin (June 2000), Madrid (January 2001), Helsinki (September 2001), London (April 2002), Warsaw (November 2002) and Seville (October 2003). The EuroVar members have agreed on several issues, and we present these in the form of a consensus statement, together with a review of the questions associated with varicella epidemiology, disease burden and vaccination policy in different European countries, as well as a discussion on the barriers to implementation of varicella vaccination.

EPIDEMIOLOGY AND DISEASE BURDEN

The epidemiology and disease burden associated with VZV infection are likely to have a direct impact on vaccination policies.

However, given that routine reporting is not mandatory in many European countries, there is a lack of precise information on varicella epidemiology and disease burden in Europe. Nevertheless, in the last few years, several studies have been published. A review of European varicella seroprevalence data indicates that in Western Europe, ~10% of individuals are still susceptible to varicella in early adulthood. 6 The data suggest that seroprevalence among adolescents and young adults is higher in Northern and Central Europe than in Southern Europe, although differences in study design preclude a direct comparison.

In Germany ~760,000 varicella cases occur per year, 7 and seroprevalence rates of 62.5 and 94.2% have been reported in children of 4 to 5 years and 10 to 11 years old, respectively. 8 Based on an analysis of 119 healthy children with severe varicella complications, the incidence rate of severe varicella complications has been calculated at 8.5 per 100,000 cases, when the data were extrapolated to 14,025,867 children up to the age of 16 years hospitalized in Germany in 1997. 9 This study also showed that varicella was associated with considerable morbidity. Neurologic symptoms (61.3%) constituted the most common complication; encephalitis and cerebellitis were seen throughout the age of 1 to 13 years. Superinfections of the skin have been observed in 35.2% of healthy children with cellulitis and abscesses as the common diagnosis. The leading cause of cellulitis was group A β-hemolytic streptococci followed by Staphylococcus aureus and Staphylococcus epidermidis. Pyrogenic arthritis was seen in 4.2% and osteomyelitis in 3.3% of patients. Five percent of patients had chronic sequelae after infectious complications. 10 This is similar to data reported from France. 11 Sixty-eight children of whom 76.5% were healthy were admitted to French Pediatric Intensive Care Units from 1998 to 2001. Bacterial infections accounted for 47% of cases (including skin and soft tissue infections in 20 cases) and 38% for neurologic complications including 10 encephalitis.

Analysis of routine mortality data indicated that between 1995 and 1997 in England and Wales, 25 people a year on average died from varicella, with an overall case fatality rate of 9.22 per 100,000 consultations for varicella. The total number of cases was 826,881, based on consultation rates for this period. 12 The authors concluded that varicella is not a mild disease. Using a variety of primary care-based data sources, Edmunds et al. 13 estimated 260,955 episodes of herpes zoster in England and Wales annually, with an average of 44 deaths a year since 1995.

Varicella has been a notifiable disease in Scotland since 1988, which has allowed the generation of detailed data on varicella epidemiology. During the period 1989 to 1998, an average of 32,908 cases of varicella were reported each year from a population of 5.1 million, whereas in 1998 there were 435 general practice consultations for varicella per 100,000 population. Furthermore between 1981 and 1998, there were a total of 44 deaths, although none of these deaths was in infants younger than 1 year of age. 14

In France the Sentinelle System is used for surveillance of the main communicable diseases, and involves collection of weekly data from ~500 Sentinelle General Practitioners. Between 1991 and 1995 a total of 15,817 cases of varicella were reported, which when extrapolated to the French population equates to an annual incidence of varicella of 1.0 to 1.35 cases per 100 inhabitants. 15 Ninety-two percent of cases occurred in children <14 years, with a complication rate of 2%. Common complications were skin superinfections, lower and upper respiratory tract infections, conjunctivitis and corneal infections and central nervous system complications.

In Italy, where each of the 20 regions is autonomously responsible for the implementation of vaccine strategies, varicella has been a notifiable disease since 1934. Because every child is followed by a pediatrician, the exact number of patients without complication is known. Since 2000 a nationwide sentinel system (SPES) has been established based on surveys of >450 pediatricians and covering ~5% of the pediatric population. 16 Among 384,000 children, 20,513 cases of varicella were notified, giving an overall incidence rate of 5.3%, ranging from 6.3% in the north to 4.8% in the south. 17 The Pedianet study shows a similar incidence rate (6.3%, rising to 8% among the susceptibles), whereas the rate calculated by the official notifications during that year is only 0.98%. Complications have been reported in 3.5 to 5% of childhood cases, the most frequent being upper respiratory tract (1.3%) and cutaneous (0.9%) infections, but none was reported to be severe; hospitalizations rates were in the range of 0.2 to 0.35% (C Giaquinto, personal communication, 2002). 18 There is a marked seasonal peak in spring and incidence is highest among 4-year-olds. The official case-mortality statistics for 1997 list 45 deaths related to VZV, all in individuals >40 years of age. Seroepidemiologic data from two independent Italian studies confirmed geographic variations and also indicate the highest rate (18–22%) of seronegative adolescents and young adults in Europe (M Romano, personal communication, 2002). 19

A seroepidemiologic study performed in the Catalonia region of Spain showed a seroprevalence rate of 85 and 92% in the 5-to 9-and 10-to 14-year-old age group, respectively. 20 Analysis of national hospitalization data showed 3632 varicella-related discharges during 1995 to 1998, representing an annual hospitalization rate of 2.8 per 100,000 population. 21 These data indicate that varicella is associated with substantial severe morbidity in Spain.

In countries where there remains a lack of information about varicella, several studies and initiatives are currently in progress to increase knowledge in this area. This will improve the information available to health authorities, physicians and parents, therefore permitting more effective management of the disease.

In the United States, before implementation of the varicella vaccination program, there was a trend toward a decrease in the age of onset of varicella, thought to be related to the increased use of day-care facilities for young children 22–25 In the United States in the early 1990s, the highest age-specific incidence was in the preschool years, consistent with findings from England and Wales, 26,27 Scotland, 14 France, 16 Italy 18,19 and Slovenia. 28 Although studies among military recruits questioned whether varicella rates were increasing among adults, follow-up studies based on data obtained between 1990 and 1997 showed a decrease in the incidence of varicella hospitalization rates among US active duty soldiers. 29

DISEASE MANAGEMENT

A number of options are available for the treatment of VZV infections, and the approach selected depends on a number of factors, including the risk of complications in the infected individual. Disease management is based on symptomatic treatment and the use of antiviral agents, such as acyclovir for varicella and valacyclovir and famcyclovir for HZ. However, antiviral drug therapy has a limited effect and must be administered as soon as possible after the onset of rash. Therefore prevention of infection by vaccination, rather than treatment of the disease, is the optimum approach in the management of varicella.

VACCINATION POLICY

WHO recommends that routine childhood immunization may be considered in countries where the disease is a relatively important public health and socioeconomic problem, the vaccine is affordable and high and sustained coverage can be achieved. 30

In addition WHO recommends that the vaccine may be offered to individual adults and adolescents without a history of varicella.

It is expected that once a universal childhood varicella vaccination is introduced, rates of varicella disease will decline among children and adults. However, because cases will decline more in young children, a higher proportion of the total number of cases will occur in older age groups. Widespread use of varicella vaccination has been adopted in several countries, including Canada, Japan, Korea, Australia, Uruguay, Finland and the US. In the US the varicella vaccine has been licensed since 1995 and is recommended for routine use in healthy children by the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics. Both provide detailed recommendations on varicella vaccination and recommend routine vaccination of children 12 to 18 months of age 4,5 or 12 months or older, respectively. 31,32 To determine the impact of varicella vaccination in the US, passive surveillance (using data collected by the National Notifiable Disease Surveillance System) and active surveillance (in Antelope Valley, CA; Travis County, TX; West Philadelphia, PA) are being conducted. The results of active surveillance during 1995 to 2000 showed that varicella disease decreased substantially, with varicella cases declining by 71, 84 and 79% in California, Texas and Pennsylvania, respectively. 24 The greatest decrease was among children 1 to 4 years old, although cases declined in all age groups. By 2000 vaccine coverage in children ages 19 to 35 months was 82.1, 73.6 and 83.8% in these states, respectively. Data from the US National Immunization Survey showed that in 2000, 67.8% of children 19 to 35 months of age received one dose of varicella vaccine. 33 The goal is to achieve 90% coverage by 2010. These surveillance data from the US confirm the changes expected from the introduction of universal vaccination and provide reassurance that implementation of the varicella vaccination program has reduced the varicella disease burden among both children and adults. 24

Although the data produced in the United States are encouraging and valuable, the US situation cannot be applied directly to Europe given the differences in immunization procedures and practices, vaccination costs and cultural background. These factors also vary considerably between different European countries, as do the varicella vaccine license status and current vaccination recommendations (Table 1). For example Finland is the only European country to date that has adopted a universal childhood vaccination policy; recommendations state that all children older than 12 months of age and adolescents with no history of varicella should be immunized.

T1-2
TABLE 1:
Current Varicella Vaccination Recommendations in Different European Countries

BARRIERS TO VACCINATION

A number of issues surrounding varicella vaccination directly impact vaccination policy in different European countries. These are discussed below.

Disease Perception.

Varicella is generally regarded as a mild childhood disease, and some countries do not currently perceive varicella vaccination as a priority. However, varicella and HZ can be associated with severe complications, and the seriousness of VZV infection as a public health issue is becoming clearer as country-specific epidemiologic and pharmacoeconomic data become available.

Vaccine Effectiveness and Efficacy.

Concerns have been raised over the efficacy and effectiveness of the varicella vaccines. However, the vaccines have been shown to be highly immunogenic in both immunocompetent and immunocompromised children (Table 2). For example in a study of 513 healthy children 10 to 30 months of age, seroconversion rates of 99 to 100% were observed. 38 Although a lower seroconversion rate of 60% has been observed in children mildly affected with HIV, 83% had varicella-specific cell-mediated immunity. 42

T2-2
TABLE 2:
Immunogenicity of Varicella Vaccine in Children*

There is also evidence that varicella vaccines are highly effective against clinical disease. In a study of 1164 healthy children 1 to 12 years of age originally enrolled in clinical studies, an estimated vaccine efficacy of 93.8 to 94.6% was reported during a 7-year period, as assessed by comparing the observed average annual breakthrough rate with the age-adjusted expected annual incidence rate of varicella in unvaccinated children. 48 Furthermore an efficacy rate of 88.5% was observed in vaccinated individuals exposed to varicella in the household, based on an historical comparison with exposed, unvaccinated susceptible individuals. 48 Importantly the effectiveness of varicella vaccines has also been shown in healthy children in clinical practice. In a case-controlled study the vaccine was 85% effective against varicella and 97% effective against moderately severe and severe disease, based on a statistical analysis of 202 PCR-confirmed cases and their 389 matched controls without varicella. 49 Significantly more vaccinated children who developed varicella had mild disease than did unvaccinated individuals (86%vs. 48%, P < 0.001). In a postlicensure study an overall vaccine effectiveness of 83% for mild to moderate disease was observed in the day-care setting, as assessed by comparing the varicella attack rate in vaccinated vs. unvaccinated children. 50

Children up to the age of 13 years require only a single dose of varicella vaccine. However, the efficacy of the varicella vaccine is lower in adults than in children, and the ACIP therefore recommends that vaccine recipients age 13 years and older should receive two doses. 4

Another issue relating to vaccine efficacy is that of so-called “breakthrough” varicella, whereby vaccinees develop varicella from months to years after varicella vaccination. Evidence indicates that breakthrough varicella is due to reinfection with wild-type virus, rather than reactivation of the vaccine strain. 51

Breakthrough varicella is a modified illness and is generally mild. 52 Typical breakthrough rates range from 10 to 20%, 53 although a rate of 34% has been reported in a Japanese study. 54 The reasons for this high breakthrough rate are unclear, but it may be related to the regional epidemiology of varicella and to the dose of vaccine given. 38 Moreover, studies in which different doses of vaccine have been used do indicate that breakthrough rates may be related to the vaccine dose, because there is a direct relationship between the dose and the efficacy/effectiveness of the vaccine. 34,38,54–58 Consequently there has been much discussion about whether using two doses could increase protection against varicella.

Vaccine Safety.

The fact that the varicella vaccine contains live virus has been a cause of concern, but extensive studies in both clinical trial and postlicensure settings have shown that the varicella vaccines are well-tolerated. 28,35,59,60 The most common side effects in clinical trials included mild pain and redness at the injection site, mild rash and fever. 30,35 Over 20 years of experience in both immunocompromised and healthy vaccinees have shown serious adverse events to be extremely rare. 53 In postlicensure studies there have been reports of ataxia, anaphylaxis and thrombocytopenia temporally associated with vaccine administration. 61 However, there is no direct evidence that these were indeed caused by the vaccine, and most or all were probably unrelated. 53 Transmission of the vaccine viral strain from vaccinees with a rash to susceptible immunocompetent persons is rare: ~16 million doses of vaccine administered; only three cases have been reported; and even they developed only mild disease. 5

Another safety issue raised by the live varicella vaccine is the incidence of subsequent zoster. Many studies have shown that the incidence of HZ in immunocompromised children who received the vaccine is less than that among those who have had a natural infection. 53 Children with acute leukemia develop herpes zoster early after natural infection and much more frequently (a 122-fold higher incidence) than children without malignancy; for this reason they have been the focus of a number of studies. These studies have shown that the incidence of zoster in leukemic recipients of varicella vaccine is significantly lower than the incidence of zoster after natural infection. 63–66 Although the varicella vaccines have been reported to occasionally cause HZ, 61,62 the incidence in 7000 vaccinated healthy children and adolescents appeared to be lower than expected compared with those who had experienced natural varicella. 67 Also (Merck & Co., unpublished data) in a cohort study, the risk of herpes zoster in 9454 healthy children after immunization with Oka/Merck vaccine was ~18 per 100,000 person years of observation (8 cases in 44,994 person-years followed) compared with an expected rate of 77 per 100,000 person-years among healthy children after natural varicella infection. 68

Vaccination Coverage.

In many countries health authorities are apprehensive about whether high enough vaccination coverage can be achieved to prevent the formation of an unvaccinated population at risk of delayed and thus more severe disease. A theoretical model of the effects of routine varicella immunization of preschool children in the US with the use of three different coverage rates, 50%, 70% and 97%, predicted that although there would be proportionally more varicella cases in individuals >30 years old, none of these coverage rates would result in overall increased morbidity. 69 Furthermore the shift would not be as evident if a catch-up program in 12-year-olds was implemented. Indeed catch-up vaccination of susceptible children 19 months–12 years of age is recommended in the US. Concerns over the effect of mass varicella vaccination on the incidence of HZ have been raised. The reason for this is that the trigger for VZV reactivation, although not yet fully understood, is thought to depend on a decline in cell-mediated immunity, and contact with infected cases is one of the mechanisms proposed for boosting immunity. Although mathematical models have suggested that the greater the reduction in incidence of varicella, the greater is the ensuing incidence of HZ in the shorter term, 70 clinical data collected from CDC-funded surveillance in the US has revealed that no increase in HZ is evident in any age group with the introduction of mass varicella vaccination. 24,71–73 This discrepancy may be related to the fact that the changes in HZ epidemiology predicted by the mathematical models assume that external boosting is the sole determinant of immunity. Although there is some indirect evidence from adults living with and without children to suggest that exposure to varicella does boost immunity to VZV, 74 the role of boosting on HZ risk is not clear, and it has also been suggested that subclinical reactivation of the virus may boost immunity and offer protection. 75 The need to continue monitoring HZ incidence is well-recognized and should address these concerns. If necessary, immunity could be boosted by vaccination.

The likelihood of achieving a high coverage rate should improve if the varicella vaccine is combined with the existing measles-mumps-rubella (MMR) schedule, using a tetravalent MMR-varicella (MMR-V) vaccine, providing a more convenient method of administration of the vaccine to children. Early data indicate that safety issues associated with this combined approach are unlikely.

Duration of Protection.

Another apprehension concerning the varicella vaccine is that immunity wanes, which could lead to the development of varicella later in life when the disease consequences are generally far more serious. However, existing evidence indicates that immunity after vaccination is not short term. In the US a study of 60 children and 18 adults showed that 93% of children and 94% of adults had VZV antibodies 5 years after immunization, whereas 87 and 94%, respectively, had cell-mediated immunity to VZV. 76 Furthermore antibodies have been shown to persist in 100% (413 of 413) of vaccinated children after 6 years, 48 whereas after long term follow-up (>49 months), 86% of health care workers vaccinated against varicella were seropositive. 46 A recent report by Ampofo et al. 77 in vaccinated adults showed that there was no increase in the attack rate of breakthrough varicella or severity of breakthrough varicella for a 21-year interval beginning in 1979, suggesting that immunity does not wane significantly after vaccination in adults. In Japan, where widespread vaccination has now been adopted, antibody persistence and cell-mediated immunity rates of 100% were observed in a 20-year follow-up of 26 adults vaccinated as children. 78

OTHER VARICELLA VACCINATION ISSUES

Pregnancy.

As with all live vaccines, varicella vaccination is contraindicated during pregnancy, and it is advised that pregnancy be avoided for 1 to 3 months after vaccination. In a study of 362 pregnant women inadvertently exposed to varicella vaccine, no abnormal features or cases of congenital varicella syndrome were reported. 79 It should be stressed, however, that no firm conclusions can be drawn from this study because of the small sample size.

In contrast maternal varicella during pregnancy can have serious consequences for both mother and child. 80–82 The mother is at higher risk of complications, such as pneumonia. From 2 to 3% of fetuses can develop congenital varicella syndrome as a result of maternal infection during the first and second trimesters of gestation. Severe neonatal varicella can occur because of perinatal maternal infection. 83

Immunocompromised Individuals.

Immunocompromised individuals, including cancer patients, transplant recipients and HIV-positive children, are at increased risk of developing severe varicella, with high rates of morbidity and mortality. 42,84,85 Under certain conditions, immunocompromised individuals can be vaccinated against varicella (e.g. HIV-infected children in CDC class I with mild or no signs or symptoms). 42 However, such individuals can also be protected indirectly by immunization of health care workers and close (family) contacts. They would also be protected by herd immunity in countries with high levels of immunization against varicella, as would pregnant women. Indeed family contacts of immunocompromised persons are another priority group for vaccination because of their close contact with persons at high risk for serious complications.

Health Care Workers.

The costs and public health impact of varicella disease in hospital settings have been well-documented. 86–91 In the US health care workers are designated as a priority group for vaccination because of their close contact with persons at high risk for severe disease. Given that nosocomial VZV problems are likely to be universal, vaccination of health care workers should be strongly considered even in countries where a childhood vaccination program is not a high priority. It has been reported that up to 30% of vaccinated health care workers may have undetectable concentrations of VZV antibodies years after vaccination. 46 Experience with following up a cohort of 120 vaccinated health care workers, most of whom participated in clinical trials and received either Varivax or Varilrix vaccine, revealed that only 12 (10%) developed varicella 6 months to 8.4 years after vaccination with a mean of 40 skin vesicles, with an 18% attack rate after household exposure. 46 There was no known transmission to patients of either wild-type or vaccine-type VZV by these vaccines. In contrast the attack rate of nonimmune household contacts is 87%, 92 and the attack rate among nonimmune, unimmunized health care workers after work-related exposure to chickenpox is 85 to 100%. 93,94 Transmission of vaccine virus is rare and has been documented in immunocompetent persons by PCR analysis on only 3 occasions for 15 million doses of varicella vaccine distributed. All 3 cases resulted in mild disease without complications. 5 This suggests that there is decreased transmission by vaccinated people.

Economic Considerations.

One of the major obstacles when facing the question of whether to vaccinate against varicella infection is its is cost effectiveness. Studies have shown that in certain countries, varicella imposes a large economic burden on society (Table 3), with indirect costs (e.g. time off work to look after a sick child) constituting a significant proportion of the varicella societal economic burden. For example a study of 174 children attending child-care centers in Sydney, Australia, showed that parental absence from work and alternative child-care arrangements constituted the majority of the costs associated with varicella. 104

T3-2
TABLE 3:
Economic Impact of Varicella and Varicella Vaccination

The fact that only indirect costs are responsible for a large proportion of the economic burden partly explains the reluctance of many countries to invest in varicella vaccination; the economic burden of varicella disease must be supported by society in terms of loss of work days, whereas the cost of vaccination is supported by health departments. Although mass varicella immunization programs do not always appear to be cost effective from the health payer’s perspective, studies have shown that it would be cost-effective from a societal perspective (Table 3). The situation must be analyzed on a country-to-country basis, because it is affected by the economic infrastructure. 107,108 For example in a German analysis, where it was assumed that if the varicella vaccine was integrated into a vaccination policy such as the current MMR immunization program routine childhood vaccination at 15 months of age was cost-beneficial not only to society but also to health care payers, as work loss costs incurred by parents of infected children are reimbursed in Germany. 109 Wutzler et al. 10 noted that using a combined MMR-V vaccine will be necessary to assure the high coverage rates required to achieve these favorable cost-effective results in their study.

CONSENSUS

Taking into consideration the issues described above, which were discussed in a series of EuroVar meetings, the EuroVar members propose the following, subject to individual countries policies and priorities.

The varicella vaccine is effective and well-tolerated.

Varicella should be prevented and vaccination offered routinely to all healthy children between 12 and 18 months, and to all susceptible children before their 13th birthday. After their 13th birthday, two doses may be needed. However, routine vaccination should be implemented only if a high level of vaccine coverage can be reached over a reasonable period; otherwise vaccination of susceptible adolescents can be an option. Furthermore the waning of specific immunity in the vaccinated population should be carefully monitored to determine whether boosting is required, although the existence of breakthrough cases and the effect of vaccination on HZ epidemiology must also be kept under scrutiny.

If routine vaccination is implemented during early childhood, then a “catch-up” vaccination should be offered to adolescents at 12 years and older and to adults who have no reliable history of varicella.

Vaccination should be offered to health care workers and other healthy adults at high risk of exposure and transmission, including: teachers of young children; day-care center employees; military personnel and other groups living or working in institutional settings; nonpregnant women of childbearing age; and men living in households with pregnant women and/or children.

A future MMR-V vaccine will enhance the implementation of universal varicella vaccination and represents the way forward.

Extensive efforts must be made to improve the knowledge about varicella epidemiology in Europe.

The financial benefit for society as a whole should be stressed.

The public should be educated about the benefits and risks of varicella vaccination.

CONCLUDING REMARKS

Clearly many factors need to be considered before a country decides whether to implement varicella vaccination. There is also the choice of which policy to adopt, for example whether to introduce universal childhood vaccination or to target susceptible adolescents and adults. Arguments in favor of routine childhood vaccination are: varicella vaccination is more effective in young children; disease burden is greatest in children, so that public health benefits will be greatest with childhood vaccination; children serve as sources of infection to adults, infants and other groups who are not eligible for vaccination (e.g. pregnant women and immunocompromised individuals); achieving sufficient coverage is logistically easier.

A universal childhood varicella vaccination program would ultimately prevent the spread of the disease, protect high risk patients, potentially prevent cases of HZ and alleviate the costs involved in managing varicella patients. By adopting this approach the epidemiologic control of varicella is a clear possibility. EuroVar is sponsored by the VZVRF, the world’s only nonprofit organization solely fostering research and education on the VZV and VZV infections.

ACKNOWLEDGMENTS

We thank Nancy Thiry (Antwerp, Belgium) and Judith Breuer (London, UK) for their contribution and Nadine Stouvenakers (Liège, Belgium) for her assistance as scientific secretary of EuroVar.

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        APPENDIX

        The EuroVar members: F. Berthet, Luxembourg; D. Carrington, Bristol, UK; R. Cohen, Paris, France; J. Diez-Domingo, Valencia, Spain; E. Förster-Waldl, Vienna, Austria; W. Hryniewicz, Warsaw, Poland; P. Jacobs, Venlo, The Netherlands; A. Leça, Lisbon, Portugal; A. Linde, Stockholm, Sweden; L. Notarangelo, F. Schumacher, Brescia, Italy; J. Senterre, Liège, Belgium; J. Seward, Atlanta, GA; N. Stouvenakers, Liège, Belgium; T. Vesikari, Tampere, Finland; P. Van Damme, Antwerp, Belgium; P. Wutzler, Jena, Germany.

        Keywords:

        Vaccination policy; varicella-zoster virus; epidemiology; pharmacoeconomics; consensus

        © 2004 Lippincott Williams & Wilkins, Inc.