Challenges in confirming a varicella outbreak in the two-dose vaccine era

Background

A second dose of varicella vaccine was recommended for U.S. children in 2006. We investigated a suspected varicella outbreak in School District X, Texas to determine 2-dose varicella vaccine effectiveness (VE).

Methods

A varicella case was defined as an illness with maculopapulovesicular rash without other explanation with onset during April 1–June 10, 2011, in a School District X student. We conducted a retrospective cohort in the two schools with the majority of cases. Lesion, saliva, and environmental specimens were collected for varicella-zoster virus (VZV) PCR testing. VE was calculated using historic attack rates among unvaccinated.

Results

In School District X, 82 varicella cases were reported, including 60 from Schools A and B. All cases were mild, with a median of 14 lesions. All 10 clinical specimens and 58 environmental samples tested negative for VZV. Two-dose varicella vaccination coverage was 66.4% in Schools A and B. Varicella VE in affected classrooms was 80.9% (95% CI: 67.2–88.9) among 1-dose vaccinees and 94.7% (95% CI: 89.2–97.4) among 2-dose vaccinees in School A, with a second dose incremental VE of 72.1% (95% CI: 39.0–87.3). Varicella VE among School B students did not differ significantly by dose (80.1% vs. 84.2% among 1-dose and 2-dose vaccinees, respectively).

Conclusion

Laboratory testing could not confirm varicella as the etiology of this outbreak; clinical and epidemiologic data suggests varicella as the likely cause. Better diagnostics are needed for diagnosis of varicella in vaccinated individuals so that appropriate outbreak control measures can be implemented.     

Neurological complications of varicella in childhood: Case series and a systematic review of the literature

Although varicella has usually an uncomplicated course in early childhood, several neurological complications may occur. We conducted a study to review the type and the rate of varicella neurological complications in a case series of hospitalized immunologically healthy children over nearly a 8 year period. We also systematically reviewed data from the literature to estimate the rate of varicella neurological complications. In our case reports, the proportion of neurological complications among all those hospitalized for varicella was of 21.7% (CI 17.9-26%). The pooled prevalence of neurological complications resulting from the systematic review of the literature identifies the likelihood of such complications in the range of 13.9-20.4%. Although neurological complications of chickenpox do not frequently result in permanent sequelae, they represent significant determinants of prolonged hospital stay and of other indirect costs. The obtained results may be useful for estimating costs associated with hospitalization from varicella in cost-benefit analysis for immunization.     

烟台市15岁以下儿童水痘发病特征及危险因素分析

目的 分析烟台市15岁以下儿童水痘发病特征及危险因素,为烟台市水痘防控工作提供理论依据。方法 收集2011-2015年烟台市15岁以下儿童水痘的发病特征进行描述性分析;采取病例对照研究方法,对水痘危险因素进行调查分析。结果 2011-2015年烟台市15岁以下儿童水痘发病占病例总数的48.73%,10~14岁年龄组所占构成比最高(占39.33%);发病率呈逐年下降趋势,4~6岁下降幅度最大,达48.80%,其他年龄组均有不同程度的下降。发病高峰为每年的11-1月份和4-6月份,分别占42.60%和31.34%。所有地区均有水痘病例报告,城市高于农村。儿童水痘病例以轻型和中型为主,97.78%的病例无并发症。86.74%的水痘病例无水痘疫苗免疫史。分析结果显示,水痘病人接触史、带状疱疹病人接触史、医院就诊史可能是水痘发病的危险因素,接种水痘疫苗是水痘发病的保护因素。结论 做好水痘病例的管理及加强水痘疫苗接种可有效预防水痘的发生。     

Report of varicella outbreak in a low vaccination coverage group of otherwise healthy children in Italy: the role of breakthrough and the need of a second dose of vaccine

We describe an outbreak of varicella at a preschool center in Southern Italy, in the period January–May 2009, among children with a vaccination coverage of 53.9% for one dose.     

北京市房山区儿童水痘自然免疫现状横断面调查

目的 掌握北京市房山区儿童水痘自然免疫现状,为今后有效开展水痘预防与控制提供流行病学依据.方法 采用横断面调查的方法,选取有代表性的1～14岁健康儿童作为研究对象,进行问卷调查和血样采集,采用酶联免疫吸附法检测血清水痘IgG抗体.结果 648名儿童水痘抗体阳性率为44.1%;抗体阳性率在不同性别、户籍间差别无统计学意义(P＞0.05),在不同年龄和地区间儿童水痘抗体阳性率差别有统计学意义(P＜0.01),3～5岁年龄组、山区儿童水痘抗体阳性率最低,分别为30.6%和34.4%.结论 该地区儿童水痘抗体阳性率偏低,尚不能形成有效的免疫屏障,山区和3～5岁儿童是重点保护地区和人群,需采取有效措施加强这一薄弱环节的水痘预防管理与控制工作.     

The first case of Nocardia transvalensis infection in varicella in a previously immunocompetent child

A child referred to Infectious Disease Unit for varicella complicated by pneumonia with pleural effusion. Due to not improvement, laboratory search was extended to uncommon pathogens, revealing Nocardia transvalensis infection.It is likely that varicella induced immunodepression, facilitating opportunistic infection in an otherwise healthy and immunocompetent child. To our knowledge, our report is the first case of Nocardia infection in varicella.     

Evaluation of Australia's varicella vaccination program for children and adolescents

Objective

This paper examines how the monovalent varicella vaccine for children, with an adolescent catch-up dose, was introduced into Australia's National Immunisation Program (NIP), focusing on programme implementation.

Methods

Semi-structured interviews were conducted with key informants involved in programme implementation. Key themes from interviews were identified through content analysis. Childhood coverage was assessed using data from the Australian Childhood Immunisation Register (ACIR) with adolescent coverage obtained from state/territory immunisation programmes. Seroprevalence data were analysed from national serosurveys conducted before and after programme commencement.

Results

Implementation challenges for both parents and providers included: (a) parental report of previous infection as an exclusion criterion; (b) introducing a vaccine on its own at 18 months of age; and (c) adding the adolescent dose into existing school-based vaccination programmes with parental reported exclusion criteria. Despite these challenges, coverage rapidly reached 83% by 24 months of age and 30–33% for the adolescent catch-up dose. When considered in conjunction with estimated pre-vaccination natural immunity in both target groups (20% and 83%, respectively) coverage can be considered high. The serosurvey under-estimated coverage in 2-year-old children but was useful to assess trends in population immunity.

Conclusion

The introduction of a single dose of monovalent varicella vaccine at 18 months of age and a school-based catch-up programme at 11–13 years of age successfully achieved high coverage, notwithstanding some challenges. Reported natural infection has been an exclusion criterion for vaccination, but as the programme matures and circulation of wild-type virus decreases, the need for this warrants consideration. There is a need for sensitive laboratory assays to measure vaccine-induced immunity at a population level.     

水痘疫苗接种儿童水痘IgG水平的横断面研究

[目的] 观察儿童1剂水痘疫苗（VarV）免疫的持续效果及其影响因素,初探加强免疫方案。[方法] 采集≤12岁接种1剂水痘疫苗的健康儿童手指末梢血629份,用定量酶联免疫吸附试验（ELISA）测定水痘IgG水平,同时调查VarV记录和水痘患病史。[结果] 儿童水痘IgG浓度值呈偏态分布,P₂₅为40.19 mIU/mL,P₅₀为96.42 mIU/mL,P₇₅为290.82 mIU/mL,抗体对数值为（2.02±0.69） mIU/mL（95%CI：1.97～2.07）。不同接种年限和不同年龄组抗体浓度值差异有统计学意义（F=2.723,P=0.006和F=3.933,P=0.002）。儿童水痘IgG阳性率为69.0%,本地儿童抗体阳性率显著高于外来儿童（χ²=3.934,P=0.047）。抗体阳性率按VarV接种年限呈U形分布,拐点在接种后4年。[结论] 水痘疫苗接种后4年IgG浓度值降到低点,易受水痘感染。建议儿童在接种第一剂满3年后,加强1剂VarV免疫以获更有效免疫保护。     

上海市部分地区儿童水痘疫苗免疫后流行病学效果观察

[目的]观察水痘疫苗接种情况和接种水痘疫苗1~7年后的水痘发病情况。[方法]在本市部分地区选择接种组和未接种组儿童,采用统一调查问卷调查水痘疫苗接种情况和水痘发病情况。[结果]调查地区儿童水痘疫苗累积接种率为4.12%,12岁以下人群为26.90%。1999~2005年接种组总发病率为1.00%,未接种组为4.35%,水痘疫苗接种保护率为77.0%;各年接种组发病率分别为1.62%、2.06%、0.29%、0.43%和0.66%,疫苗接种保护率在67.9%~90.3%之间;接种进口和国产水痘疫苗后水痘发病率分别为0.8%和1.0%,疫苗接种保护率分别为81.6%和75.3%。[结论]本市儿童水痘疫苗接种率呈上升趋势。水痘疫苗对接种者具有较好的保护率,进口和国产水痘疫苗的保护率相似。     

Administration of live attenuated varicella vaccine to children with cancer before starting chemotherapy

From July 1985 to February 1987, of 46 consecutive children with cancer (26 male, 20 female; median age, 4 years) with no prior history of chickenpox, the initial 30 patients were randomized either to receive or not to receive live attenuated varicella vaccine (LAVV) before chemotherapy was started and the remaining 16 patients were all immunized without randomization. Before immunization, Varicella zoster (VZ) antibodies were detected by immunofluorescence and ELISA in 11 (34%) of 32 vaccinated children and two (14%) of 14 controls, indicating previous infection. A booster effect was evident in 70% of them and no side effects were noted. Ten (28%) of 32 vaccinees were excluded from the analysis because of early death due to cancer (1–4 weeks). Seroconversion was demonstrated in ten (77%) of 13 vaccinees, with high antibody titres. Only three of them lost their antibodies 2 years after immunization, as disclosed by serological follow-up. Eight out of 13 vaccinees had household contacts with VZ and none became infected. Zoster immunoglobulin (ZIG) was never given. Among controls, seven out of 14 were exposed to VZ and four (57%) became infected. Mild side effects were observed in four (12.5%) out of 32 vaccinees (three with papulovesicular rash, 6—30 lesions, and one with a 3-day intermittent fever). Local reactions, zoster and spreading of vaccinal virus did not occur. LAVV proved to be safe and effective when administered before starting chemotherapy to children with cancer and no history of varicella.     

学校缺勤缺课监测对于水痘监测的作用

目的通过分析学校缺勤缺课监测系统中因水痘缺课的数据,探讨其对水痘监测的作用。方法收集2010学年第一学期监测数据,通过描述性分析并与网络直报水痘资料进行比较,评价缺勤缺课监测的及时性、敏感性等特征。结果 2010学年第一学期共计监测97d,1 644所学校因水痘缺课3 287人、20 202人天。缺课率和缺课天数在高发期(11～12月)要高于其他月份。52.11%水痘病例来自小学。网络直报病例缺课天数要长于未网络直报病例(P<0.05)。对于就诊病例网络直报的及时性要好于学校缺勤缺课监测。结论学校缺勤缺课监测对于水痘缺课的报告与网络直报系统基本一致,而前者对于那些未就诊的轻症水痘病例具有更高的监测价值,学校缺勤缺课监测系统未来应侧重于基于症状的症候群监测。     

水痘疫苗在学校水痘暴发疫情中保护效果的病例对照研究

目的 评价接种1剂水痘疫苗在学校水痘暴发疫情中的保护效果(vaccine effectiveness, VE)。方法 采用1:2配对病例对照研究,收集中山市2013—2021年水痘暴发疫情调查资料,将病例数≥5例的班的所有病例（共942例）作为病例组,按1:2的比例选取同班、同年龄（±1岁）、同性别的1 884名健康儿童作为对照组,调查其水痘疫苗接种史,采用条件logistic回归分析水痘疫苗保护效果。结果 共调查3～14岁儿童2 826名,儿童接种1剂水痘疫苗的保护效果为58%（95%CI:50%～66%）,3～5岁、6～14岁儿童接种1剂水痘疫苗保护效果分别为75%（95%CI:62%～83%）和51%（95%CI:40%～61%）。儿童接种1剂后≤2年、3～5年、6～8年、≥9年的保护效果分别为78%（95%CI:66%～86%）、66%（95%CI:57%～74%）、51%（95%CI:36%～62%）、23%（95%CI:-11%～46%）。儿童接种1剂水痘疫苗的保护效果随接种后时间的延长而降低（趋势χ²=13.071,P<0.001）。结论 儿童接种1剂水痘疫苗有助于防控水痘暴发疫情,但其保护效果随接种后时间的延长而降低,难以阻断水痘传播。建议儿童及时接种2剂水痘疫苗,以预防学校水痘暴发疫情。     

2005-2018年上海市奉贤区水痘流行病学特征分析

目的 分析上海市奉贤区2005-2018年水痘流行病学特征,为制定水痘防控措施提供参考依据。 方法 通过中国疾病预防控制信息系统收集上海市奉贤区2005-2018年水痘报告病例,采用描述性流行病学方法进行分析。 结果 上海市奉贤区2005-2018年共报告10493例水痘病例,年平均发病率为75.10/10万;各年发病率在16.40/10万（2006年）-107.25/10万（2010年）之间。发病时间高峰在10-12月（3652例,占总病例的34.80%）。发病年龄以5~9岁（占总病例的26.09%）和15~19岁（占总病例的17.73%）为主,男性病例多于女性病例,男女性别比为1.30[DK]∶1。2005-2018年发生水痘暴发疫情91起,突发公共卫生事件6起,主要发生在学校、幼托机构等集体单位。 结论 儿童是水痘的高发人群,水痘疫情主要集中在幼托机构和学校,应继续加强监测;同时建议加大宣传力度,提高儿童家长水痘疫苗接种意识。     

北京市怀柔区水痘免疫策略调整后的流行病学特征

目的 了解北京市怀柔区水痘的发病特征与流行趋势,比较水痘疫苗接种程序调整前后流行病学特征的变化,评价水痘疫苗使用现状,为今后制定水痘防控措施提供流行病学依据.方法 对怀柔区2009-2013年水痘监测资料及疫苗使用资料进行描述流行病学分析.结果 2009-2013年水痘发病数为1 507例,较多的月份为1和10月份;5～9岁年龄组发病数占29.12％;学生发病数占47.42％;2013年自费水痘疫苗使用量为9 610支,较2010-2012年年均使用量增加了155.25％.结论 2013年怀柔区水痘免疫策略调整后,水痘发病率显著下降,流行病学特征与免疫策略调整前没有实质性变化.     

A varicella outbreak in a school with high one-dose vaccination coverage, Beijing, China

Background

Varicella vaccine is available in the private sector in China, with a single dose currently recommended for children aged ≥12 months. We investigated a varicella outbreak in a school in Beijing with high varicella vaccination coverage to describe the outbreak, examine risk factors for vaccine failure, and calculate vaccine effectiveness.

Methods

A varicella case was defined as an acute generalized maculopapular rash without other apparent cause in a student without prior varicella attending the elementary school during August 30–December 28, 2010. Varicella among vaccinated students (breakthrough varicella) was defined as varicella occurring >42 days after vaccination. Students’ vaccination status was verified with immunization records and clinical presentations were collected from health care practitioners.

Results

Of the 951 students, 934 (98%) had no prior varicella history. Among these students, 916 had received 1 dose of varicella vaccine and 2 had received 2 doses (98% vaccination coverage) before the outbreak. A total of 87 cases occurred during the outbreak; most had breakthrough varicella (86/87, 99%) and mild disease (83/87, 95%). Age at vaccination (<15 months vs. ≥15 months) and time since vaccination before outbreak (<5 years vs. ≥5 years) were not associated with development of breakthrough varicella. Single-dose varicella vaccination was 89% effective in preventing any varicella and 99% in preventing moderate/severe varicella.

Conclusion

Single-dose varicella vaccination is highly effective in reducing varicella incidence and mitigating disease severity, but not high enough to prevent outbreak. A two-dose program might help to prevent varicella outbreaks in Beijing.     

Immune response of varicella vaccinees to different varicella-zoster virus genotypes

The objective was to verify specific antibody response of varicella vaccinees to varicella-zoster virus (VZV) strains of different major clades and subclades circulating currently in Germany. The neutralization test and the fluorescent antibody to membrane antigen test measuring VZV glycoprotein (gp)-specific antibodies were used as methods. All VZV strains clustering into the main clades 1, 3 and 5 were neutralized by vaccine-induced antibodies and showed specific reaction with VZVgp-specific antibodies of vaccinees. In conclusion, this study provides first experimental evidence that varicella vaccines based on the Japanese Oka strain induce antibody response directed to VZV strains circulating currently in Germany.     

The epidemiology of varicella cases among children in Beijing's Fengtai District from 2008 to 2012

In recent years, the number of breakthrough cases of varicella (onset >42 days after vaccination) increased each year, and varicella outbreaks continue to occur in Beijing. Data from the Immunization Information System and the Infectious Disease Reporting System demonstrated that in Beijing's Fengtai District, the varicella breakthrough rate increased from 0.7% in 2008 to 2.5% in 2012 and showed an increased trend (P < 0.001). Among the varicella cases in children (age of 3–15 years), the number of breakthrough cases increased from 167 in 2008 to 622 in 2012, which was 45.2% (n = 1735) of the total child cases (n = 3842). From 2008 to 2012, a total of 62 outbreaks occurred; among the 787 affected child outbreak cases, 61% were vaccinated. Altogether, the results from this study indicated that 1-dose vaccination cannot sufficiently prevent the occurrence of breakthrough cases of varicella or control varicella outbreaks in Beijing's Fengtai District.     

The utility of serologic testing for varicella in an adolescent population

The purpose of this study was to determine what proportion of adolescents without a history of varicella are seropositive, and if serologic testing of this adolescent subpopulation is cost-effective. We identified 122 patients with ‘no’ or ‘unknown’ histories of chicken pox from our adolescent clinic. Of these, 58 (48%) were found to be Varicella Zoster Virus (VZV) seropositive. Cost to the government for batched serologic testing of all unknowns was $682.65, while each adolescent vaccinated cost $59.60. Serologic testing prior to routine immunization of adolescents with unclear varicella histories saved $2774.15 (38% of routine immunization costs). In this population, serologic testing is more cost effective than routinely immunizing all unknowns.     

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.