Influenza Immunization of Children in India

描述（由申请人提供）：研究的设计与正在进行的项目相同，但是，计划了两个主要的子目标。流感在印度的短暂流行表明，目前的秋季免疫接种时间表可能不是最佳的。拟议的研究将提供关于疫苗接种时间的数据，这将对热带环境产生广泛影响。具体目标1：描述流感疫苗的直接和间接功效。在一项前瞻性、对照、家庭随机、观察者盲法研究中，通过确定儿童疫苗接种在印度3个农村儿童及其家庭成员中减少流感的功效来完成。建议分两个阶段进行：第一阶段：用多个疫苗年份继续确定对流感的疗效。流感疫苗的效力部分取决于与流行病毒的抗原匹配。由于大流行，2009年的疫苗接种匹配度较差，2010年的疫苗接种匹配度较好，如果2011年秋季（按要求）的疫苗接种提供匹配度，通过监测到2012年5月，可以评估秋季接种后2-3年的累积保护效果。这时，第二阶段开始了。第2阶段：确定在印度北部季风流感高峰期之前接种的疫苗的效力。德里地区夏季出现流感高峰，冬季出现次要高峰。我们假设，在印度北部夏季流感高峰期之前的晚春接种流感疫苗，与目前在秋季接种疫苗相比，将在流感活动最活跃的时期提供更好的保护。我们建议测试时间的变化，在2012年5月和2013年5月进行免疫接种，随访至2014年5月。这将衡量秋季和春季免疫接种后的直接和间接保护，并延长数据年份，同时不影响研究的总体目标。这一方案可能导致决策者调整流感疫苗接种时间的建议。具体目标2。定义流感临床疾病和结果。流感的临床表现，包括合并症和流感相关的并发症，记录了在研究村包括16000人的每周积极监测。此外，对其他非流感呼吸道病毒的检测将估计它们对这一人群的疾病贡献。总之，拟议的研究将确定接种流感病毒疫苗的幼儿是否不仅能保护已接种疫苗的儿童，还能保护他们周围的其他儿童和成人，并将确定在印度和其他流感季节性相似的地区接种疫苗的适当时机。

DESCRIPTION (provided by applicant): The design of the study remains the same as the ongoing project, however, two major sub-objectives are planned. The temporal circulation of influenza in India suggests the current fall immunization schedule may not be optimal. The proposed study will provide data on vaccine timing that will have broad implications in tropical settings. Specific Aim 1: Describe influenza vaccine direct and indirect efficacy. Accomplished by determining the efficacy of vaccination of children in decreasing influenza in children and their family members in 3 rural villages in India in a prospective, controlled, household randomized, observer blinded study. Two phases are proposed: Phase 1: Continue determination of efficacy against influenza with multiple vaccine years. The efficacy of influenza vaccine depends in part on antigenic match with circulating viruses. Vaccination in 2009 had a poor match due to the pandemic, 2010 vaccination had an improved match and if vaccination in fall 2011 (as requested here) provides a match, with surveillance until May 2012 a cumulative protective effect can be assessed for 2-3 years after fall administration. At this time, phase 2 begins. Phase 2: To determine the efficacy of vaccine administered prior to the monsoon influenza peak in Northern India. The largest peak of influenza is observed in summer in the Delhi region, with minor peaks in winter. We hypothesize that influenza vaccination in late spring prior to the influenza peak in summer in Northern India will confer significantly better protection during the period of highest influenza activity, compared to the current vaccination regimen in the fall of the year. We propose to test a change of timing, immunizing in May 2012 and 2013, with follow-up until May 2014. This will measure direct and indirect protection after both fall and spring immunization and extend the years of data, without compromising the overall objectives of the study. This regimen may lead policy makers to adjust recommendations for the timing of influenza vaccination. Specific Aim 2. Define influenza clinical disease and outcomes. The clinical presentations of influenza, including co-morbid conditions and influenza-related complications are recorded from active weekly surveillance in the study villages comprising >16,000 persons. Furthermore testing for other non-influenza respiratory viruses will estimate their contribution to disease in this population. In summary, the proposed studies will determine whether immunization of young children with influenza virus vaccine protects not only the immunized children but also the other children and adults who are around them, and will identify the appropriate timing of vaccine administration in India and other regions with similar influenza seasonality.