Department of Pediatrics, School of Medicine, and Center for Global Health, School of Public Health, University of Colorado Denver, Denver, CO, USA.
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
Lancet Glob Health. 2019 Jul;7(7):e940-e950. doi: 10.1016/S2214-109X(19)30079-8.
Paediatric vaccination against influenza can result in indirect protection, by reducing transmission to their unvaccinated contacts. We investigated whether influenza vaccination of children would protect them and their household members in a resource-limited setting.
We did a cluster-randomised, blinded, controlled study in three villages in India. Clusters were defined as households (ie, dwellings that shared a courtyard), and children aged 6 months to 10 years were eligible for vaccination as and when they became age-eligible throughout the study. Households were randomly assigned (1:1) by a computer-based system to intramuscular trivalent inactivated influenza vaccine (IIV3) or a control of inactivated poliovirus vaccine (IPV) in the beginning of the study; vaccination occurred once a year for 3 years. The primary efficacy outcome was laboratory-confirmed influenza in a vaccinated child with febrile acute respiratory illness, analysed in the modified intention-to-treat population (ie, children who received at least one dose of vaccine, were under surveillance, and had not an influenza infection within 15 days of last vaccine dose). The secondary outcome for indirect effectiveness (surveillance study) was febrile acute respiratory illness in an unvaccinated household member of a vaccine study participant. Data from each year (year 1: November, 2009, to October, 2010; year 2: October, 2010, to October, 2011; and year 3: October, 2011, to May, 2012) were analysed separately. Safety was analysed among all participants who were vaccinated with at least one dose of the vaccine. This trial is registered with ClinicalTrials.gov, number NCT00934245.
Between Nov 1, 2009, to May 1, 2012, we enrolled 3208 households, of which 1959 had vaccine-eligible children. 1010 households were assigned to IIV3 and 949 households were assigned to IPV. In 3 years, we vaccinated 4345 children (2132 with IIV3 and 2213 with IPV) from 1868 households (968 with IIV3 and 900 with IPV) with 10 813 unvaccinated household contacts. In year 1, influenza virus was detected in 151 (10%) of 1572 IIV3 recipients and 206 (13%) of 1633 of IPV recipients (total IIV3 vaccine efficacy 25·6% [95% CI 6·8-40·6]; p=0·010). In year 2, 105 (6%) of 1705 IIV3 recipients and 182 (10%) of 1814 IPV recipients had influenza (vaccine efficacy 41·0% [24·1-54·1]; p<0·0001). In year 3, 20 (1%) of 1670 IIV3 recipients and 81 (5%) of 1786 IPV recipients had influenza (vaccine efficacy 74·2% [57·8-84·3]; p<0·0001). In year 1, total vaccine efficacy against influenza A(H1N1)pdm09 was 14·5% (-20·4 to 39·3). In year 2, total vaccine efficacy against influenza A(H3N2) was 64·5% (48·5-75·5). Total vaccine efficacy against influenza B was 32·5% (11·3-48·6) in year 1, 4·9% (-38·9 to 34·9) in year 2, and 76·5% (59·4-86·4) in year 3. Indirect vaccine effectiveness was statistically significant only in year 3 (38·1% [7·4-58·6], p=0·0197) when influenza was detected in 39 (1%) of 4323 IIV3-allocated and 60 (1%) of 4121 IPV-allocated household unvaccinated individuals. In the IIV3 group, 225 (12%) of 1632 children in year 1, 375 (22%) of 1718 in year 2, and 209 (12%) of 1673 in year 3 had an adverse reaction (compared with 216 [13%] of 1730, 380 [21%] of 1825, and 235 [13%] of 1796, respectively, in the IPV group). The most common reactions in both groups were fever and tenderness at site. No vaccine-related deaths occurred in either group.
IIV3 provided variable direct and indirect protection against influenza infection. Indirect protection was significant during the year of highest direct protection and should be considered when quantifying the effect of vaccination programmes.
US Centers for Disease Control and Prevention.
儿童接种流感疫苗可通过减少对其未接种疫苗的接触者的传播，从而产生间接保护作用。我们研究了在资源有限的环境下，儿童接种流感疫苗是否会对他们及其家庭成员产生保护作用。
我们在印度的三个村庄进行了一项整群随机、双盲、对照研究。以家庭（即共用一个庭院的住所）为单位进行分组，所有年龄在 6 个月至 10 岁之间的儿童，在整个研究期间，只要符合年龄要求，就可以接种疫苗。通过计算机系统将家庭随机分配（1:1）到接种三价灭活流感疫苗（IIV3）或对照的灭活脊髓灰质炎疫苗（IPV）组；每年接种一次，共 3 年。主要疗效结局为在接种疫苗的发热性急性呼吸道感染患儿中，实验室确诊的流感，分析人群为接受至少一剂疫苗、正在接受监测且最后一剂疫苗接种后 15 天内无流感感染的儿童（即改良意向治疗人群）。间接效果（监测研究）的次要结局为疫苗接种研究参与者的未接种家庭接触者发生发热性急性呼吸道感染。每年（第 1 年：2009 年 11 月至 2010 年 10 月；第 2 年：2010 年 10 月至 2011 年 10 月；第 3 年：2011 年 10 月至 2012 年 5 月）的数据分别进行分析。所有接种至少一剂疫苗的参与者的安全性进行了分析。本试验在 ClinicalTrials.gov 注册，编号为 NCT00934245。
2009 年 11 月 1 日至 2012 年 5 月 1 日期间，我们共纳入 3208 个家庭，其中 1959 个家庭有符合接种疫苗条件的儿童。1010 个家庭被分配到 IIV3 组，949 个家庭被分配到 IPV 组。在 3 年期间，我们为 1868 个家庭（968 个家庭接种了 IIV3，900 个家庭接种了 IPV）的 4345 名儿童（2132 名接种了 IIV3，2213 名接种了 IPV）进行了疫苗接种，共有 10133 名未接种疫苗的家庭接触者。在第 1 年，1572 名 IIV3 接种者中有 151 名（10%）和 1633 名 IPV 接种者中有 206 名（13%）检测到流感病毒（IIV3 疫苗总有效率为 25.6%[95%CI 6.8-40.6]；p=0.010）。在第 2 年，1705 名 IIV3 接种者中有 105 名（6%）和 1814 名 IPV 接种者中有 182 名（10%）感染了流感（IIV3 疫苗有效率为 41.0%[24.1-54.1]；p<0.0001）。在第 3 年，1670 名 IIV3 接种者中有 20 名（1%）和 1786 名 IPV 接种者中有 81 名（5%）感染了流感（IIV3 疫苗有效率为 74.2%[57.8-84.3]；p<0.0001）。第 1 年，流感 A（H1N1）pdm09 的总疫苗效力为 14.5%（-20.4%至 39.3%）。第 2 年，流感 A（H3N2）的总疫苗效力为 64.5%（48.5%至 75.5%）。第 1 年，流感 B 的总疫苗效力为 32.5%（11.3%至 48.6%），第 2 年为 4.9%（-38.9%至 34.9%），第 3 年为 76.5%（59.4%至 86.4%）。仅在第 3 年，流感病毒在 4323 名 IIV3 分配的未接种疫苗的家庭接触者中检测到 39 例（1%），在 4121 名 IPV 分配的未接种疫苗的家庭接触者中检测到 60 例（1%）时，间接疫苗效力具有统计学意义（38.1%[7.4%至 58.6%]，p=0.0197）。在 IIV3 组中，第 1 年有 1632 名儿童中有 225 名（12%）、第 2 年有 1718 名儿童中有 375 名（22%）、第 3 年有 1673 名儿童中有 209 名（12%）出现不良反应（相比之下，在 IPV 组中，第 1 年有 1730 名儿童中有 216 名（13%）、第 2 年有 1825 名儿童中有 380 名（21%）、第 3 年有 1796 名儿童中有 235 名（13%）出现不良反应）。两组中最常见的反应是发热和接种部位触痛。两组均未发生与疫苗相关的死亡。
IIV3 对流感感染提供了可变的直接和间接保护。在直接保护效果最强的那一年，间接保护具有显著意义，在量化疫苗接种计划的效果时应考虑到这一点。
美国疾病控制与预防中心。
