Chickenpox: sufficient reasons for the introduction of vaccination

The incidence of chickenpox and its complications is high enough to favour introducing varicella vaccination into the Dutch immunisation programme for children, although current Dutch figures may even underestimate the incidence. Safe and effective MMRV vaccines, in which varicella (V) vaccine is combined with measles, mumps and rubella (MMR), could well replace the MMR vaccine used at present. MMRV vaccines should be administered subcutaneously in two doses. Ten years after the introduction of varicella vaccination in the United States of America, the incidence of complications has decreased impressively. An effect on the incidence of herpes zoster has not (yet) been seen.     

Universal varicella vaccine immunization in Japan

In 1974, Japanese scientists developed a live attenuated varicella vaccine based on the Oka strain. The efficacy of the vaccine for the prevention of varicella has been primarily demonstrated in studies conducted in the United States following the adoption of universal immunization using the Oka strain varicella vaccine in 1996. Although the vaccine was developed by Japanese scientists, until recently, the vaccine has been administered on a voluntary basis in Japan resulting in a vaccine coverage rate of approximately 40%. Therefore, Japan initiated universal immunization using the Oka strain varicella vaccine in November 2014. Given the transition from voluntary to universal immunization in Japan, it will also be important to monitor the epidemiology of varicella and herpes zoster.The efficacy and safety of co-administration of the varicella vaccine and measles, mumps, and rubella vaccine have been demonstrated in many countries; however, there was no data from Japan. In order to adopt the practice of universal immunization using the Oka strain varicella vaccine in Japan, data demonstrating the efficacy and safety of co-administration of varicella vaccine and measles and rubella (MR) vaccine were required. Additionally, we needed to elucidate the appropriate time interval between the first and second administrations of the vaccine. It is also important to differentiate between wild type and Oka vaccine type strains in herpes zoster patient with past history of varicella vaccine. Thus, there are many factors to consider regarding the adoption of universal immunization in Japan to control varicella zoster virus (VZV) infections.     

Modeling the impact of combined vaccination programs against varicella and herpes zoster in Norway

BackgroundAdoption of varicella immunization in Europe is limited due to a predicted increase in the incidence of herpes zoster (HZ) resulting from a removal of exogenous boosting by varicella vaccination. Most available assessments of immunization strategies only considered universal varicella vaccination (alone or in combination with HZ by the live vaccine). The development of a new subunit recombinant zoster vaccine may provide new perspectives of HZ control.MethodsWe used a mathematical model for VZV in Norway based on the progressive immunity formulation of exogenous boosting. We evaluated a complete range of alternative immunization options against varicella and HZ including both universal and targeted varicella vaccination, either alone or with zoster immunization, and zoster immunization alone. We considered all values of the boosting intensity consistent with the Norwegian HZ incidence and compared the performance of the currently available live vaccine vs. a new recombinant vaccine.ResultsUniversal varicella vaccination alone resulted in a marked increase in the incidence of HZ under all scenarios considered. Even under the most favorable hypotheses on the magnitude of the boosting intensity, this increase could be mitigated only by a parallel HZ immunization with a recombinant vaccine, assuming a long duration of protection. Targeted varicella immunization of adolescents resulted in a modest increase in the HZ incidence which could be counterbalanced by both the live and, especially, the recombinant vaccine.ConclusionsGiven current knowledge on HZ pathogenesis and exogenous boosting, targeted varicella vaccination of adolescents was the only strategy that was not predicted to impact the epidemiology of HZ, and therefore it may represent a suitable alternative to universal vaccination. These results are aimed to support vaccine policy decisions in Norway and other countries with a similar VZV epidemiology.     

Predicting and comparing long-term measles antibody profiles of different immunization policies

OBJECTIVE: Measles outbreaks are infrequent and localized in areas with high coverage of measles vaccine. The need is to assess long-term effectiveness of coverage. Since 1991, no measles epidemic affecting the whole island has occurred in Taiwan, China. Epidemiological models are developed to predict the long-term measles antibody profiles and compare the merits of different immunization policies on the island. METHODS: The current measles immunization policy in Taiwan, China, is 1 dose of measles vaccine at 9 months of age and 1 dose of measles, mumps and rubella (MMR) vaccine at 15 months of age, plus a 'mop-up' of MMR-unvaccinated schoolchildren at 6 years of age. Refinements involve a change to a two-dose strategy. Five scenarios based on different vaccination strategies are compared. The models are analysed using Microsoft Excel. FINDINGS: First, making the assumption that measles vaccine-induced immunity will not wane, the predicted measles IgG seroprevalences in preschool children range from 81% (lower bound) to 94% (upper bound) and in schoolchildren reach 97-98% in all strategy scenarios. Results are dependent on the association of vaccine coverage between the first and second dose of vaccine. Second, if it is assumed that vaccine-induced antibody titres decay, the long-term measles seroprevalence will depend on the initial titres post vaccination, decay rates of antibody titres and cut-off of seropositivity. CONCLUSION: If MMR coverage at 12 months of age can reach > 90%, it would be worth changing the current policy to 2 doses at 12 months and 6 years of age to induce higher antibody titres. These epidemiological models could be applied wherever a similar stage of measles elimination has been reached.     

Development of varicella vaccine in Japan and future prospects

In Japan, Dr. Michiaki Takahashi (1928–2013) successfully developed the first live attenuated varicella vaccine in the world. The virus used for this vaccine was varicella-zoster virus isolated from the vesicular fluid of a child with typical varicella and it was named the Oka strain after the family name of the child. In 1974, a patient with nephrosis developed varicella in the Pediatric Ward, and uninfected pediatric patients received varicella vaccine immediately. As a result, there were no cases of varicella in the other children and all of the vaccinated children acquired immunity to the disease. These results were published in the Lancet, demonstrating the safety and efficacy of varicella Oka strain vaccine for the first time. When clinical studies were conducted at the start of vaccine development, most of the subjects were pediatric patients with a high risk of contracting severe varicella. Therefore, the development process was different from that for other vaccines, since clinical studies are generally performed in healthy individuals.This vaccine was approved in Japan in 1986, and voluntary single-dose vaccination for children aged 1 year or older was started in 1987. However, the vaccination coverage rate remained low and the number of patients with varicella did not decrease significantly. Due to its voluntary status, the cost of vaccination was borne by the child's family and this was considered to be a reason for the low coverage rate. Moreover, although the vaccine achieved a good antibody response, the number of cases of breakthrough varicella (BV) was relatively high and showed an increasing trend that was also a concern. In order to increase the coverage rate and reduce BV, the Japanese government changed the varicella vaccination policy from voluntary to routine vaccination in October 2014. At the same time, a two-dose schedule was introduced that involved administration of the vaccine twice at an interval of at least 3 months up to the age of 3 years.At present, cases of varicella are only monitored at the pediatric sentinel clinics in Japan. Therefore, we need to establish a system to survey all patients, in order to demonstrate the efficacy of varicella vaccine based on detailed surveillance data. We also need to investigate the optimum timing of the second dose of the vaccine and the necessity for further booster vaccination. A combined live vaccine containing varicella vaccine has not yet been approved in Japan. Because of the greater convenience of combined vaccines, development and introduction of such a vaccine in the future would be desirable. Routine varicella vaccination is also expected to eventually reduce the occurrence of herpes zoster, although there are no supporting epidemiological data. The prevalence of herpes zoster has attracted attention, but it is necessary to develop a surveillance system for this disease. In March 2016, use of varicella vaccine to prevent herpes zoster in adults aged 50 years or older was approved in Japan, and the results of this policy change need to be assessed.     

A combined measles,mumps, rubella and varicella vaccine (Priorix-Tetra™): Immunogenicity and safety profile

Priorix-Tetra™ (GlaxoSmithKline Biologicals) is a combined measles, mumps, rubella and varicella (MMRV) vaccine. Eight studies involving more than 3000 children were reviewed. Compared with co-administration of MMR (Priorix™) and varicella (Varilrix™) vaccines, the MMRV vaccine showed: similar immunogenicity, with immunity shown up to 3 years post-vaccination; a higher rate of fever after the first dose; a slight increase in mild local reactions after the second dose. This MMRV vaccine can be used either as a two-dose vaccine or as a second dose in children primed with separate MMR and/or varicella vaccines, offering a convenient way to introduce varicella vaccination into routine vaccination programmes.     

Present anti-measles immunity in Jordan.

The immunity of adults and the prevalence of measles was determined in order to evaluate the adequacy of current measles vaccination policy in Jordan. A total of 307 sera, collected from adults aged 18--40 years, were tested for anti-measles antibodies by ELISA technique. The overall prevalence of anti-measles antibodies was 94.8% and there was no significant difference in the seropositivity rate between males (95.7%) and females (94%). Of the tested adults, 71% were vaccinated and 29% escaped vaccination. In Jordan, measles outbreaks occur periodically and predominantly attack children aged 5--14 years. Our data support introducing the compulsory MMR vaccine in the year 2000 to improve the vaccination coverage of measles; since the optional single dose vaccination has not interrupted the circulation of the measles virus. A second dose of MMR vaccine could be offered to Jordanians either at school entry or at the age of 11--12 years, based on the outcome of the compulsory single dose of MMR vaccine.     

Assessment of the potency and potential immunomodulatory effects of the measles mumps rubella and varicella vaccine in infants

This study compared the potency and immunomodulatory effects of measles mumps rubella (MMR) vaccine given to infants alone or in combination with varicella (MMR and V). In an additional group, MMR vaccination was delayed 42 days to permit analysis of potential effects on underlying maturation of systemic immune functions. Assessment of immunity to the vaccines indicated consistent antibody production coupled with mixed Th1/Th2 memory, and no significant differences between vaccine groups or to the group who had their MMR vaccination delayed. Parallel analyses of cytokine responses to phytohaemagglutinin and tetanus toxoid did not detect any "bystander" effects of the vaccines on systemic immunity.     

Population-based incidence of herpes zoster after introduction of a publicly funded varicella vaccination program

Background

Past varicella infection (chicken pox) may reactivate into herpes zoster (shingles). Varicella vaccination leads to a reduction in cases of varicella that may in turn increase herpes zoster rates due to reduction in the immune boosting effect of exposure to varicella zoster virus against varicella reactivation. We assessed the impact of childhood varicella vaccination in Ontario, Canada on zoster incidence and healthcare visits, and established baseline zoster rates prior to zoster vaccine introduction.

Methods

We used population-based, administrative databases to identify zoster incidence and healthcare use from April 1992 to March 2010.

Results

After routine varicella vaccination, zoster incidence rates decreased 29% for children aged 0-9 and changed minimally for other ages. Age-standardized rates of hospitalizations during the study period declined by 53%, while outpatient rates declined by 9%. The annual zoster incidence for those 60 or older was 740 per 100,000.

Conclusions

In the early post-varicella vaccination period, incidence rates of medically attended herpes zoster did not increase for the overall population and decreased moderately for children 9 years and younger, the age group targeted for varicella vaccination.     

Identifying immunity gaps for measles using Belgian serial serology data

Vaccine-preventable diseases, such as measles, have been re-emerging in countries with moderate to high vaccine uptake. It is increasingly important to identify and close immunity gaps and increase coverage of routine childhood vaccinations, including two doses of the measles-mumps-rubella vaccine (MMR). Here, we present a simple cohort model relying on a Bayesian approach to evaluate the evolution of measles seroprevalence in Belgium using the three most recent cross-sectional serological survey data collections (2002, 2006 and 2013) and information regarding vaccine properties. We find measles seroprevalence profiles to be similar for the different regions in Belgium. These profiles exhibit a drop in seroprevalence in birth cohorts that were offered vaccination at suboptimal coverages in the first years after routine vaccination has been started up. This immunity gap is observed across all cross-sectional survey years, although it is more pronounced in survey year 2013. At present, the COVID-19 pandemic could negatively impact the immunization coverage worldwide, thereby increasing the need for additional immunization programs in groups of children that are impacted by this. Therefore, it is now even more important to identify existing immunity gaps and to sustain and reach vaccine-derived measles immunity goals.     

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.     

Assessing the introduction of universal varicella vaccination in the Netherlands

Although varicella is seen as a benign disease in the Netherlands, about 40,000 visits to a general practitioner (GP) are made, over 200 hospital admission occur, and 2.3 persons die on average each year. Most of this burden of disease can be prevented by universal varicella childhood vaccination. Ten years after the introduction of the single-shot, single-component varicella childhood vaccination in the USA, a major reduction in hospitalization, mortality, and burden of disease has been reported. Using our recently vaccine evaluation model for the introduction of a new vaccine in our national immunization program, we have analyzed the feasibility of universal varicella vaccination by replacing the measles-mumps-rubella (MMR) vaccine with a measles-mumps-rubella-varicella (MMRV) vaccine. After structuring and reviewing the available data, two major points of uncertainty remain: (1) the influence of universal childhood vaccination on the incidence of zoster later in life; (2) the cost-effectiveness ratio for the Dutch situation. Despite these uncertainties it is clear that universal childhood vaccination will prevent most of the varicella related GP-visits, hospitalizations, and deaths.     

某高校一起带状疱疹病例引起水痘疫情的调查报告

目的 了解苏州某高校一起带状疱疹病例引起水痘疫情的调查处置情况,分析疫情发生原因及控制效果,为高校传染病疫情防控提供参考经验。方法 建立带状疱疹及水痘病例定义,查看学校缺课记录、医院就诊记录、传染病疫情报告网络系统等进行病例搜索,并逐一进行个案调查。采用描述性流行病学方法分析疫情流行病学特征及传播过程。结果 本次疫情共发生1名带状疱疹病例和4名水痘病例,班级罹患率分别为1.33 %（1/75）和5.33 %（4/75）,该班级的水痘-带状疱症病毒感染罹患率为6.67%(5/75)。疫情持续33 d,控制在一个班级内。病例均为男性,病例年龄在18～20岁之间,居住在同一个宿舍楼的两个房间。1名患者有明确水痘疫苗免疫史,水痘突破发病时间与免疫接种间隔18年。结论 该高校水痘疫情为由1名带状疱疹病例传播水痘-带状疱疹病毒引起。建议高校今后加强带状疱疹和水痘疾病监测和管理,提前采取干预措施,避免疫情扩散。     

Epidemiology of measles,mumps and rubella in Italy

A serosurvey for measles, mumps and rubella was conducted in Italy; incidence based on statutory notifications over the last three decades was also calculated. In Italy the diseases followed an endemic-epidemic pattern, with an incidence peak every 2-4 years, and had a limited reduction of incidence attributable to childhood immunization. Lower notification rates were observed in the Southern regions. This is possibly related to greater under notification in the South and is confirmed by our seroprevalence data. Incidence of measles and rubella and proportion of cases among young adults increased significantly in the three decades considered, but not for mumps. Serological data confirmed that these infections are still very frequent in Italy, without significant geographic variation in the country. In the age groups 2-4 and 5-9 years the percentage of individuals still susceptible to each virus was higher than 30%. The proportion of susceptible subjects older than 15 years was similar for the three infections (6.1, 11.7 and 8.8% for measles, mumps and rubella, respectively). The low vaccine coverage for rubella and measles in Italy has so far only partially affected the occurrence of the diseases. No impact of mumps vaccination is visible. The average number of deaths, for each disease, has decreased during the three study periods. Today the priority in Italy is to halt the progressive increase of the mean age of acquisition of the three infections, to eliminate differences in coverage among regions and to conform to European standards. This will be achieved through a combination of increasing MMR vaccine coverage before 2 years of age, implementing vaccination campaigns for low seroprevalence age groups, and/or introducing a second dose of MMR, depending on the level of current MMR coverage.     

Impacts of routine varicella vaccination program and COVID-19 pandemic on varicella and herpes zoster incidence and health resource use among children in Japan

PurposeTo determine the epidemiological trends in pediatric varicella and herpes zoster incidence and changes in healthcare resource use from 2005 to 2022 using a nationally representative database in Japan.Materials and methodsWe conducted a retrospective observational study consisting of 3.5 million children with 177 million person-months during 2005–2022 using Japan Medical Data Center (JMDC) claims database in Japan. We investigated trends in incidence rates of varicella and herpes zoster and changes in healthcare resource use (e.g., antiviral use, office visits, and healthcare costs) over 18 years. Interrupted time-series analyses were used to investigate the impact of the routine varicella vaccination program in 2014 and infection prevention measures against COVID-19 on incidence rates of varicella and herpes zoster and related healthcare utilization.ResultsAfter the introduction of the routine immunization program in 2014, we observed level changes in incidence rates (45.6 % reduction [95 %CI, 32.9–56.0] of varicella cases, antiviral use (40.9 % reduction [95 %CI, 25.1–53.3]), and relevant healthcare costs (48.7 % reduction [95 %CI, 38.2–57.3]). Furthermore, infection prevention measures against COVID-19 were associated with additional level changes in varicella rates (57.2 % reduction [95 %CI, 44.5–67.1]), antiviral use (65.7 % reduction [59.7–70.8]), and healthcare costs (49.1 % [95 %CI, 32.7–61.6]). In contrast, the changes in incidence and healthcare costs for herpes zoster were relatively small, which showed 9.4 % elevated level change with a decreasing trend and 8.7 % reduced level change with a decreasing trend after the vaccine program and the COVID-19 pandemic. The cumulative incidence of herpes zoster in children born after 2014 was lower than that before 2014.ConclusionsVaricella incidence and healthcare resource use were largely affected by the routine immunization program and infection prevention measures against COVID-19, while these impacts on herpes zoster were relatively small. Our study indicates that immunization and infection prevention measures largely changed pediatric infectious disease practices.     

Incidence of herpes zoster among varicella-vaccinated children,by number of vaccine doses and simultaneous administration of measles,mumps, and rubella vaccine

IntroductionChildren may receive measles-mumps-rubella (MMR) and varicella (VAR) vaccines separately or as measles-mumps-rubella-varicella (MMRV). We examined whether pediatric herpes zoster (HZ) incidence varied by pattern of varicella vaccine administration.MethodsIn six integrated health systems, we examined HZ incidence among children turning 12 months old during 2003–2008. All received varicella and MMR vaccines on recommended schedules. Cases were identified through 2014 using ICD-9 codes. Incidence was examined by number of varicella vaccine doses and same-day MMR.ResultsAmong 199,797 children, overall HZ incidence was 18.6/100,000 person-years in the first-dose MMR + VAR group, 17.9/100,000 person-years in the MMRV group, and 7.5/100,000 person-years in the VAR-alone group. HZ incidence was lower following the second dose than before the second dose in all first-dose groups.ConclusionsHZ incidence was not meaningfully different between the MMRV and MMR + VAR first-dose groups. Overall and within first-dose groups, HZ incidence was lower among children receiving two varicella vaccine doses.     

2009年盐城市盐都区麻疹疫苗强化免疫接种分析

[目的]评价2009年盐城市盐都区麻疹强化免疫活动的实施效果,为制订麻疹的预防控制措施提供依据。[方法]2009年3月,对盐城市盐都区71 094名8月龄至14岁儿童实施麻疹强化免疫,对报告接种率、调查接种率、接种安全性、免疫前后麻疹发病情况进行评价。[结果]强化免疫接种71 094人,报告接种率为98.90%,快速评估接种率为98.38%;麻疹发病率强化免疫前1年为4.11/10万,免疫后1年为1.57/10万。18个镇的估算接种率为63.93%~115.38%,预防接种副反应发生率为4.79/万。[结论]实施麻疹疫苗强化免疫接种率较高,有效降低了麻疹发病率。     

The epidemiology of varicella and herpes zoster in The Netherlands: implications for varicella zoster virus vaccination

We studied the epidemiology of varicella (chickenpox) and herpes zoster (shingles) in The Netherlands to assess the desirability to implement routine varicella zoster virus vaccination in The Netherlands. Data on seroprevalence of varicella zoster virus in the general population (1995-1996), consultations of general practitioners for varicella (2000-2002) and herpes zoster (1998-2001) and hospital admissions due to varicella (1994-2001) and herpes zoster (1994-2001) in The Netherlands were analysed. The seropositivity increased sharply with age from 18.4% for both 0- and 1-year-olds, to 48.9%, 59.0%, 75.7% and 93.0% for 2-, 3-, 4- and 5-year-olds, respectively, and varied between 97.5% and 100% for older age groups. The average annual incidence of GP-consultations amounted to 253.5 and 325.0 per 100,000 for varicella and herpes zoster, respectively. The incidence of hospital admission due to varicella and herpes zoster was 1.3 (2.3 including side diagnosis) and 2.7 (5.8) per 100,000, respectively. Whilst for varicella, the incidence of GP-consultations and hospital admissions were highest in childhood, for herpes zoster, these were highest in elderly. Insight into epidemiology of varicella zoster is needed for the assessment of the desirability of introduction of routine varicella zoster vaccination.     

Modeling the impact of one- and two-dose varicella vaccination on the epidemiology of varicella and zoster

In many countries, policymakers are being asked to make recommendations regarding the introduction of a 2-dose varicella vaccination program. The objective of this study was to examine the potential impact of 1-dose versus 2-dose varicella vaccination programs on varicella and zoster incidence, using Canada as an example. We developed a deterministic realistic age-structured model that fits 1- and 2-dose vaccine efficacy, varicella force of infection and zoster incidence. Assuming 90% coverage, the base case model (range: min; max) predicts that 1-dose vaccination will reduce varicella and zoster cases by 64% (14%; 96%) and 5% (−2%; 22%), respectively, over 80-years. Adding a second dose is predicted to reduce varicella and zoster by an additional 22% (0%; 82%) and 6% (0%; 14%), respectively. Most varicella cases prevented by the second dose are breakthrough infections. Although the incremental effectiveness of adding the second dose is highly sensitive to vaccine efficacy and mixing, predictions of the overall benefit of a 2-dose program is relatively robust to model assumptions. Adding a 2-dose program may help guarantee high population-level effectiveness against varicella. However, the incremental benefit of a second dose is highly dependant on the effectiveness of the first dose and its impact on zoster.     

Modelling the impact of a combined varicella and zoster vaccination programme on the epidemiology of varicella zoster virus in England

This study updates previous work on modelling the incidence of varicella and Herpes Zoster (HZ) following the introduction of childhood vaccination. The updated model includes new data on age-specific contact patterns, as well as data on the efficacy of zoster vaccination in the elderly and allows for HZ among vaccinees. The current study also looks at two-dose varicella childhood programmes, and assesses the combined impact of varicella vaccination in childhood and zoster vaccination of the elderly. The results suggest that a two-dose schedule is likely to reduce the incidence of varicella to very low levels, provided first dose coverage is around 90% and second dose coverage is in excess of 70%. Single dose varicella vaccination programmes are expected to result in large numbers of breakthrough cases. Childhood vaccination is expected to increase the incidence of zoster for more than 40 years after introduction of the programme, the magnitude of this increase being influenced primarily by the duration of boosting following exposure to the varicella zoster virus. Though this increase in zoster incidence can be partly offset by vaccination of the elderly, the effectiveness of this combined strategy is limited, as much of the increase occurs in those adults too young to be vaccinated. Childhood vaccination at intermediate levels of coverage (70% and 60% for first and second dose coverage respectively) is expected to lead to an increase in adult varicella. At high coverage (90% and 80% coverage) this is unlikely to be the case. These results will be used to inform a cost-effectiveness analysis of combined varicella and zoster vaccination programmes.