Abstract
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.
Highlights
By 2050, results suggest that 74·5% 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
Older adults should be included in tuberculosis vaccine clinical development and implementation planning
There have been increasingly rapid advances in the development of new tuberculosis vaccines in the past few years, with 12 candidates in clinical trials, including four in phase 2B/3.8 2018 was an important year for tuberculosis vaccine development, with results from two new preclinical studies,[9] the late-stage H4 versus Bacillus Calmette–Guérin (BCG) revaccination[10] and M72/AS01E clinical trials,[11] and with results anticipated from the Mycobacterium vaccae trial (NCT01979900)
Summary
Despite progress in tuberculosis prevention and care during the past two decades,[1] China remains the third largest contributor to the global burden of new tuberculosis cases, accounting for 889 000 (761 000–1 030 000) new cases in 2017.2 Increasing public-sector investment in tuberculosis care has contributed to the detection of 87% of cases and treatment success in 94% of cases.[1,2] Given the substantial achievements in the scale-up of existing tuberculosis care and prevention options, mathematical modelling suggests that gains possible from further investment in existing tools alone are unlikely to reach WHO tuberculosis goals for 2025 (50% incidence reduction vs 2015), 2035 (90% reduction vs 2015), and 2050 (elimination, defined as less than one case per million people per year) in China.[3,4,5,6,7] Innovative tools, such as new tuberculosis vaccines, will be essential for achieving these targets.[3,4,5,6]There have been increasingly rapid advances in the development of new tuberculosis vaccines in the past few years, with 12 candidates in clinical trials, including four in phase 2B/3.8 2018 was an important year for tuberculosis vaccine development, with results from two new preclinical studies,[9] the late-stage H4 versus Bacillus Calmette–Guérin (BCG) revaccination[10] and M72/AS01E clinical trials,[11] and with results anticipated from the Mycobacterium vaccae trial (NCT01979900). Evidence before this study We searched the tuberculosis vaccine epidemiological modelling literature up to July 19, 2017. We searched PubMed, Embase, and the WHO Global Health Library with the search terms (“models, theoretical”[mesh]) OR “mathematical model*”) AND (TB OR tuberculosis OR “tuberculosis”[mesh]) AND (vaccin* OR immuniz* OR immunis* OR “tuberculosis vaccines”[mesh]). Previous studies suggest that targeting new vaccines to adolescents would have a greater impact than infant vaccination; no previous research has explored the potential impact of new tuberculosis vaccines targeting older adults. Two modelling studies have explored the impact of new tuberculosis vaccines in China, one compared vaccination at birth to all-age mass vaccination and one was assumed mass vaccination. Results suggested that mass vaccination, post infection, might be important for elimination in China. Age specificity in demographic and epidemic dynamics in China has not been addressed in vaccine models
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
