TB Modelling Group, TB Centre and Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
TB Modelling Group, TB Centre and Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Lancet Glob Health. 2019 Feb;7(2):e209-e218. doi: 10.1016/S2214-109X(18)30452-2. Epub 2019 Jan 7.
Tuberculosis is the leading single-pathogen cause of death worldwide, and China has the third largest number of cases worldwide. New tools, such as new vaccines, are needed to meet WHO tuberculosis goals. Tuberculosis vaccine development strategies mostly target infants or adolescents, but given China's ageing epidemic, vaccinating older people might be important. We modelled the potential impact of new tuberculosis vaccines in China targeting adolescents (15-19 years) or older adults (60-64 years) with varying vaccine characteristics to inform strategic vaccine development.
A Mycobacterium tuberculosis transmission model was calibrated to age-stratified demographic and epidemiological data from China. Varying scenarios of vaccine implementation (age targeting [adolescents or older adults] and coverage [30% or 70%]) and characteristics (efficacy [40%, 60%, or 80%], duration of protection [10 years or 20 years], and host infection status required for efficacy [pre-infection, post-infection in latency, post-infection in latency or recovered, or pre-infection and post-infection]) were assessed. Primary outcomes were tuberculosis incidence and mortality rate reduction in 2050 in each vaccine scenario compared with the baseline (no new vaccine) scenario and cumulative number needed to vaccinate (NNV) per case or death averted, 2025-50.
By 2050, results suggest that 74·5% (uncertainty interval [UI] 70·2-78·6) of incident tuberculosis cases in China would occur in people aged 65 years or older, and 75·1% (66·8-80·7) of all cases would be due to reactivation, rather than new infection. All vaccine profiles delivered to older adults had higher population-level impact (reduction of incidence and mortality rates) and lower NNV per case and per death averted than if delivered to adolescents. For an intermediate vaccine scenario of 60% efficacy, 10-year protection, and 70% coverage, the reduction of tuberculosis incidence rates with older adult vaccination was 1·9 times (UI 1·5-2·6) to 157·5 times (119·3-225·6) greater than with adolescent vaccination, and the NNV was 0·011 times (0·008-0·014) to 0·796 times (0·632-0·970) lower. Furthermore, with older adult vaccination, post-infection vaccines provided substantially greater mortality and incidence rate reductions than pre-infection vaccines.
Adolescent-targeted tuberculosis vaccines, the focus of many development plans, would have only a small impact in ageing, reactivation-driven epidemics such as those in China. Instead, an efficacious post-infection vaccine delivered to older adults will be crucial to maximise population-level impact in this setting and would provide an important contribution towards achieving WHO goals. Older adults should be included in tuberculosis vaccine clinical development and implementation planning.
Aeras and UK MRC.
结核病是全球导致死亡的首要单一病原体，中国的结核病发病人数在全球排名第三。为了实现世界卫生组织的结核病目标，需要新的工具，如新型疫苗。结核病疫苗的研发策略主要针对婴儿或青少年，但鉴于中国的老龄化疫情，为老年人接种疫苗可能很重要。我们针对中国的青少年（15-19 岁）或老年人（60-64 岁）的新型结核病疫苗进行了建模，这些疫苗具有不同的疫苗特性，旨在为战略疫苗开发提供信息。
我们使用结核分枝杆菌传播模型，根据中国的年龄分层人口统计和流行病学数据进行了校准。评估了不同的疫苗实施场景（目标人群为青少年或老年人，覆盖范围为 30%或 70%）和特性（有效性为 40%、60%或 80%，保护期为 10 年或 20 年，有效性所需的宿主感染状态为感染前、潜伏感染后、潜伏感染后或已恢复、或感染前和潜伏感染后）。主要结果是与基线（无新疫苗）情景相比，2050 年每种疫苗情景下结核病发病率和死亡率的降低，以及 2025-50 年每例病例或死亡人数所需的疫苗接种人数（NNV）。
到 2050 年，结果表明中国 74.5%（不确定区间[UI]70.2-78.6）的结核病发病病例将发生在 65 岁或以上的人群中，75.1%（66.8-80.7）的所有病例将是由于再激活而不是新感染。所有针对老年人的疫苗方案都比针对青少年的疫苗方案具有更高的人群水平影响（发病率和死亡率的降低）和更低的每例病例和每例死亡人数所需的 NNV。对于中等有效性（60%）、10 年保护期和 70%的疫苗覆盖范围的疫苗方案，老年人接种疫苗的结核病发病率降低率是青少年接种疫苗的 1.9 倍（UI 1.5-2.6）至 157.5 倍（119.3-225.6），而 NNV 则降低了 0.011 倍（0.008-0.014）至 0.796 倍（0.632-0.970）。此外，与青少年接种疫苗相比，感染后疫苗在降低死亡率和发病率方面提供了更大的效果。
青少年为目标人群的结核病疫苗是许多研发计划的重点，但在老龄化、再激活驱动的疫情（如中国的疫情）中，其影响很小。相反，针对老年人的有效感染后疫苗将是在这种环境下最大限度地提高人群水平影响的关键，并将为实现世卫组织目标做出重要贡献。老年人应纳入结核病疫苗临床研发和实施规划。
Aeras 和英国医学研究理事会。
