Leach Amanda Jane, Mulholland Edward Kim, Santosham Mathu, Torzillo Paul John, Brown Ngiare Joy, McIntyre Peter, Smith-Vaughan Heidi, Skull Sue, Balloch Anne, Andrews Ross, Carapetis Jonathan, McDonnell Joseph, Krause Vicki, Morris Peter Stanley
Child Health Division, Menzies School of Heath Research, Darwin, Northern Territory, Australia.
Centre for International Child Health, Murdoch Childrens Research Institute, University of Melbourne, Melbourne, Victoria, Australia London School of Hygiene and Tropical Medicine, London, UK.
BMJ Open. 2015 Jan 16;5(1):e007247. doi: 10.1136/bmjopen-2014-007247.
Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection.
This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM.
Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals.
ACTRN12610000544077 and NCT01174849.
几乎所有居住在北领地（NT）偏远地区的原住民婴儿在出生后的几周内就会患上中耳炎（OM）。中耳炎及相关听力损失从婴儿期一直持续到儿童期，甚至常常延续至成年期。这严重损害了他们的教育和社会机会。肺炎球菌和不可分型流感嗜血杆菌（NTHi）是导致中耳炎的主要病原体，它们在鼻咽部大量定植，并在生命早期就感染中耳。我们的假设是，与目前的单一疫苗接种方案相比，从1月龄开始接种联合疫苗可能会提供更早、更广泛的保护。
这项随机、结局评估者设盲的对照试验将招募425名年龄在28至38天之间的婴儿，并将他们随机分配（1:1:1）到三种肺炎球菌结合疫苗（PCV）接种方案中的一种：2、4、6月龄接种葛兰素史克公司生产的Synflorix，2、4、6月龄接种辉瑞公司生产的沛儿13，或1、2、4月龄接种Synflorix并在6月龄接种沛儿13的试验性接种方案。7月龄时的设盲主要结局是特定疫苗抗原的免疫原性（几何平均浓度（GMC）以及GMC高于阈值0.35μg/L的参与者比例）。所有时间点的次要结局是额外的免疫原性指标、疫苗型肺炎球菌和NTHi鼻咽部携带的参与者比例，以及任何中耳炎情况，包括任何鼓膜穿孔。对家长的访谈将提供有关中耳炎常见风险因素的数据。
已获得北领地卫生部和孟席斯人类研究伦理委员会（EC00153）、澳大利亚中部人类研究伦理委员会（EC00155）以及西澳大利亚原住民健康伦理委员会（WAAHEC - 377 - 12/2011）的伦理批准。最终试验结果、数据分析、解读和结论将以适当的书面和口头形式呈现给家长和监护人、参与的社区、地方、国家和国际会议，并发表在同行评审的开放获取期刊上。
ACTRN12610000544077和NCT01174849。
