<i>Haemophilus influenzae</i> type b disease in the era of conjugate vaccines: critical factors for successful eradication

Prior to implementation of <i>Haemophilus influenzae</i> type b (Hib)-conjugate vaccination programs in the 1990s, Hib was the commonest cause of bacterial meningitis in children aged &lt;5 years. While the burden of all Hib disease has significantly decreased in the post-vaccination era, Hib still accounted for &gt;29,000 deaths worldwide in children aged &lt;5 years in 2015. We reviewed literature data on the most widely used Hib vaccines and vaccination strategies which led to the global prevention and control of Hib disease and aim to highlight important factors for continued disease control and elimination in the future. More than 90% of countries worldwide have implemented Hib-conjugate vaccination in their national immunization programs. Vaccines containing Hib polyribosylribitol phosphate (PRP) conjugated with tetanus toxoid (Hib-TT) are the most commonly used. <i>Neisseria meningitidis</i> outer membrane protein complex of PRP (Hib-OMP) is also used. Although the kinetics of the immune response varies with Hib vaccine and schedule used, high control of Hib disease was observed in all settings/scenarios. Further improving global Hib vaccination coverage may result in disease elimination. <b>What is the context?</b> Haemophilus influenzae is causing a variety of diseases, from otitis media and sinusitis to invasive disease (e.g. meningitis and pneumonia). H. influenzae type b (Hib) was the most common cause of bacterial meningitis in children &lt;5 years of age, and especially among &lt;2-year-olds. Even with appropriate treatment, up to 40% of children with bacterial meningitis can suffer permanent disabilities and up to 5% will die. The development of vaccines to protect against Hib disease has started in the late 1970s and has culminated with the licensure of 4 Hib conjugate vaccines, of which 2 are currently widely used. <b>What is new?</b> In this review, we gathered evidence on the different Hib vaccines and vaccination strategies that have contributed to the global prevention and control of Hib disease. The review indicates: the incidence of Hib disease has decreased considerably due to the introduction of Hib vaccines in national immunization programs worldwide. However, Hib disease is not yet completely eradicated. the vaccines currently used offer protection against Hib over long periods of time. carriage of the pathogen by healthy individuals seem to be less frequent, but data are still needed to fully evaluate the impact of vaccination. other H. influenzae types are now more frequent. <b>Why is this important?</b> Despite the huge success of Hib vaccination, continuous surveillance is needed to anticipate potential re-emergences and devise the best strategies for prevention and control of disease. Hib vaccination should be considered in the few countries who have not yet implemented it, to decrease associated morbidity and mortality.在20世纪90年代实施b型流感嗜血杆菌（Haemophilus influenzae type b, Hib）结合疫苗接种计划之前，Hib是5岁以下儿童细菌性脑膜炎的最常见病因。尽管在后疫苗接种时代，所有Hib相关疾病的疾病负担已大幅下降，但2015年全球仍有超过29000名5岁以下儿童因Hib感染死亡。我们回顾了全球范围内用于预防和控制Hib疾病的最广泛使用的Hib疫苗及接种策略的文献数据，旨在明确未来持续开展疾病控制与消除工作的关键要点。 目前全球已有超过90%的国家将Hib结合疫苗纳入国家免疫规划。最常用的疫苗为含Hib多聚核糖基核糖醇磷酸盐（polyribosylribitol phosphate, PRP）与破伤风类毒素结合的制剂（Hib-TT）；Hib与脑膜炎奈瑟菌（Neisseria meningitidis）外膜蛋白复合物结合的疫苗（Hib-OMP）也有应用。尽管免疫应答动力学因所用Hib疫苗及接种程序而异，但所有接种场景下均实现了对Hib疾病的高效控制。进一步提升全球Hib疫苗接种覆盖率或可实现疾病消除。 **背景**：流感嗜血杆菌（Haemophilus influenzae）可引发多种疾病，从中耳炎、鼻窦炎到侵袭性疾病（如脑膜炎与肺炎）。b型流感嗜血杆菌（Hib）曾是5岁以下儿童，尤其是2岁以下儿童细菌性脑膜炎的最常见病因。即便接受规范治疗，仍有高达40%的细菌性脑膜炎患儿会遗留永久性残疾，另有至多5%的患儿会死亡。针对Hib疾病的疫苗研发始于20世纪70年代末，最终有4种Hib结合疫苗获得上市许可，其中2种目前已得到广泛应用。 **新进展**：本综述汇总了有助于全球Hib疾病预防与控制的各类Hib疫苗及接种策略的相关证据。本综述表明：随着全球各国将Hib疫苗纳入国家免疫规划，Hib疾病的发病率已大幅下降；但目前Hib疾病尚未完全根除。当前使用的疫苗可长期为机体提供针对Hib的保护。健康个体的病原体带菌状态似乎有所减少，但仍需更多数据以全面评估疫苗接种的影响。其他血清型的流感嗜血杆菌感染现已更为常见。 **重要意义**：尽管Hib疫苗接种已取得巨大成功，但仍需开展持续监测，以预判潜在的疫情复燃，并制定最优的疾病预防与控制策略。对于尚未实施Hib疫苗接种的少数国家，应考虑将其纳入免疫规划，以降低相关疾病的发病率与死亡率。