Ortiz Justin R, Goswami Doli, Lewis Kristen D C, Sharmeen Amina Tahia, Ahmed Moshtaq, Rahman Mustafizur, Rahman Mohammed Z, Feser Jodi, Neuzil Kathleen M, Brooks W Abdullah
PATH, Seattle, WA, USA; University of Washington, Departments of Global Health and Medicine, Seattle, WA, USA.
International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Vaccine. 2015 Jun 26;33(29):3415-21. doi: 10.1016/j.vaccine.2015.04.048. Epub 2015 Apr 24.
Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings.
We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations.
Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events.
In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted.
减毒活流感疫苗（LAIVs）对于在资源匮乏地区为儿童进行免疫接种而言，具有价格可承受、效果显著且在后勤保障方面切实可行的潜力。
2012年，我们在孟加拉国达卡对24至59个月大的儿童开展了一项关于俄罗斯主干季节性三价LAIV安全性的II期随机、双盲、平行组、安慰剂对照试验。接种疫苗后，我们通过每周家访以及在研究诊所进行监测，对参与者进行为期六个月的观察，以了解主动和被动报告的不良事件、方案定义的喘息疾病（PDWI）以及严重不良事件（SAE），包括所有原因导致的住院情况。
300名儿童被随机分组并接种LAIV（n = 150）或安慰剂（n = 150）。两组在接种疫苗后均未出现即时反应。在接种疫苗后的前7天以及整个试验期间，主动报告的反应在疫苗组和安慰剂组之间相似。在整个试验过程中，LAIV组和安慰剂组出现PDWI的参与者之间无统计学显著差异（n = 13 vs. n = 16，p = 0.697）。在研究开始时有哮喘或喘息病史且接受过治疗或住院的131名儿童中，65名接受了LAIV，66名接受了安慰剂。在这一子集中，LAIV组和安慰剂组在整个试验期间出现PDWI的情况无统计学差异（7.7% vs. 19.7%，p = 0.074）。虽然没有相关的严重不良事件，但LAIV接种者出现了6起非相关严重不良事件，而安慰剂接种者未出现严重不良事件。这些严重不良事件包括3起因创伤性损伤和骨折，以及1起因对乙酰氨基酚意外过量、腹痛和急性肠胃炎各1起。出现严重不良事件的参与者在事件发生时均无实验室确诊的流感、喘息疾病或其他急性呼吸道疾病迹象。
在这项针对孟加拉国城市300名24至59个月大儿童的随机对照试验中，俄罗斯主干LAIV安全且耐受性良好。有必要在更大队列中进一步评估LAIV的安全性和有效性。
