Glasser John W, Feng Zhilan, Omer Saad B, Smith Philip J, Rodewald Lance E
National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Department of Mathematics, College of Science, Purdue University, West Lafayette, IN, USA.
Lancet Infect Dis. 2016 May;16(5):599-605. doi: 10.1016/S1473-3099(16)00004-9. Epub 2016 Feb 5.
Vaccination programmes to prevent outbreaks after introductions of infectious people aim to maintain the average number of secondary infections per infectious person at one or less. We aimed to assess heterogeneity in vaccine uptake and other characteristics that, together with non-random mixing, could increase this number and to evaluate strategies that could mitigate their impact.
Because most US children attend elementary school in their own neighbourhoods, surveys of children entering elementary school (age 5 years before Sept 1) allow assessment of spatial heterogeneity in the proportion of children immune to vaccine-preventable diseases. We used data from a 2008 school-entry survey by the Immunization Division of the California Department of Public Health to obtain school addresses; numbers of students enrolled; proportions of enrolled students who had received one or two doses of the measles, mumps, and rubella (MMR) vaccine; and proportions with medical or personal-belief exemptions. Using a mixing model suitable for spatially-stratified populations, we projected the expected numbers of secondary infections per infectious person for measles, mumps, and rubella. We also mapped contributions to this number for measles in San Diego County's 638 elementary schools and its largest district, comprising 200 schools (31%). We then modelled the effect on measles' realised reproduction number (RV) of the following plausible interventions: vaccinating all children with personal-belief exemptions, increasing uptake by 10% to 50% in all low-immunity schools (<90% of students immune) or in only influential (effective daily contact rates >3 or contacts inter-school >30%) low-immunity schools, and increasing private school uptake to the public school average.
In 2008, 39 132 children began elementary school in San Diego County, CA, USA. At entry to school, 97% had received at least one dose of the MMR vaccine, with 2·5% having personal-belief exemptions. We note substantial heterogeneity in immunity throughout the county. Although the average population immunities for measles, mumps, and rubella (92%, 87%, 92%) were similar to the population-immunity thresholds in homogeneous, randomly-mixing populations (91%, 88%, 76%), after accounting for heterogeneity and non-random mixing, the basic reproduction numbers increased by 70%, meaning that introduced pathogens could cause outbreaks. The impact of our modelled interventions ranged from negligible to a nearly complete reduction in the outbreak potential of measles. The most effective intervention to lower the realised reproduction number (RV 3·39) was raising immunity by 50% in 114 schools with low immunity (RV 1·02), but raising immunity by this level in only influential, low-immunity schools also was effective (RV 2·02). The effectiveness of vaccinating the 972 children with personal-belief exemptions was similar to that of targeting all low-immunity schools (RV 1·11). Targeting only private schools had little effect.
Our findings suggest that increasing vaccine uptake could prevent outbreaks such as that of measles in San Diego in 2008. Vaccinating children with personal-belief exemptions was one of the most effective interventions that we modelled, but further research on mixing in heterogeneous populations is needed.
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为防止在感染源引入后爆发疫情而开展的疫苗接种计划旨在将每名感染者的二代感染平均数量维持在1或更低水平。我们旨在评估疫苗接种率及其他因素的异质性,这些因素与非随机混合共同作用可能会增加这一数字,并评估可减轻其影响的策略。
由于大多数美国儿童在其所在社区的小学上学,因此对即将进入小学(9月1日前满5岁)的儿童进行调查,可评估对疫苗可预防疾病具有免疫力的儿童比例的空间异质性。我们使用了加利福尼亚州公共卫生部免疫司2008年入学调查的数据,以获取学校地址、入学学生人数、已接种一剂或两剂麻疹、腮腺炎和风疹(MMR)疫苗的入学学生比例,以及有医疗或个人信仰豁免的学生比例。使用适合空间分层人群的混合模型,我们预测了麻疹、腮腺炎和风疹每名感染者的预期二代感染数量。我们还绘制了圣地亚哥县638所小学及其最大的学区(包含200所学校,占31%)中麻疹对这一数字的贡献情况。然后,我们模拟了以下合理干预措施对麻疹实际繁殖数(RV)的影响:为所有有个人信仰豁免的儿童接种疫苗;在所有低免疫学校(免疫学生比例<90%)或仅在有影响力的(有效日常接触率>3或校际接触>30%)低免疫学校将接种率提高10%至50%;以及将私立学校的接种率提高到公立学校的平均水平。
2008年,美国加利福尼亚州圣地亚哥县有39132名儿童开始上小学。入学时,97%的儿童已接种至少一剂MMR疫苗,2.5%的儿童有个人信仰豁免。我们注意到全县的免疫情况存在很大异质性。尽管麻疹、腮腺炎和风疹的平均人群免疫率(92%、87%、92%)与同质、随机混合人群中的人群免疫阈值(91%、88%、76%)相似,但在考虑异质性和非随机混合后,基本繁殖数增加了70%,这意味着引入的病原体可能引发疫情。我们模拟的干预措施的影响范围从可忽略不计到几乎完全降低麻疹的爆发潜力。降低实际繁殖数(RV 3.39)最有效的干预措施是在114所低免疫学校将免疫率提高50%(RV 1.02),但仅在有影响力的低免疫学校将免疫率提高到这一水平也有效(RV 2.02)。为972名有个人信仰豁免的儿童接种疫苗的效果与针对所有低免疫学校的效果相似(RV 1.11)。仅针对私立学校几乎没有效果。
我们的研究结果表明,提高疫苗接种率可预防如2008年圣地亚哥麻疹疫情那样的爆发。为有个人信仰豁免的儿童接种疫苗是我们模拟的最有效干预措施之一,但需要对异质人群中的混合情况进行进一步研究。
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