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@ARTICLE{Harris:142914,
      author       = {R. C. Harris and T. Sumner and G. M. Knight and T. Evans
                      and V. Cardenas and C. Chen$^*$ and R. G. White},
      title        = {{A}ge-targeted tuberculosis vaccination in {C}hina and
                      implications for vaccine development: a modelling study.},
      journal      = {The lancet / Global health Global health [...]},
      volume       = {7},
      number       = {2},
      issn         = {2214-109X},
      address      = {Oxford},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2019-00542},
      pages        = {e209 - e218},
      year         = {2019},
      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.},
      cin          = {C070},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30630775},
      doi          = {10.1016/S2214-109X(18)30452-2},
      url          = {https://inrepo02.dkfz.de/record/142914},
}