title: Tuberculosis control strategies to reach the 2035 global targets in China: the role of changing demographics and reactivation disease.
abstract: BACKGROUND
  In the last 20 years, China ramped up a DOTS (directly observed treatment, short-course)-based tuberculosis (TB) control program with 80% population coverage, achieving the 2015 Millennium Development Goal of a 50% reduction in TB prevalence and mortality. Recently, the World Health Organization developed the End TB Strategy, with an overall goal of a 90% reduction in TB incidence and a 95% reduction in TB deaths from 2015-2035. As the TB burden shifts to older individuals and China's overall population ages, it is unclear if maintaining the current DOTS strategy will be sufficient for China to reach the global targets.
  
  
  METHODS
  We developed an individual-based computational model of TB transmission, implementing realistic age demographics and fitting to country-level data of age-dependent prevalence over time. We explored the trajectory of TB burden if the DOTS strategy is maintained or if new interventions are introduced using currently available and soon-to-be-available tools. These interventions include increasing population coverage of DOTS, reducing time to treatment, increasing treatment success, and active case finding among elders > 65 years old. We also considered preventative therapy in latently infected elders, a strategy limited by resource constraints and the risk of adverse events.
  
  
  RESULTS
  Maintenance of the DOTS strategy reduces TB incidence and mortality by 42% (95% credible interval, 27-59%) and 41% (5-64%), respectively, between 2015 and 2035. A combination of all feasible interventions nears the 2035 mortality target, reducing TB incidence and mortality by 59% (50-76%) and 83% (73-94%). Addition of preventative therapy for elders would enable China to nearly reach both the incidence and mortality targets, reducing incidence and mortality by 84% (78-93%) and 92% (86-98%).
  
  
  CONCLUSIONS
  The current decline in incidence is driven by two factors: maintaining a low level of new infections in young individuals and the aging out of older latently infected individuals who contribute incidence due to reactivation disease. While further reducing the level of new infections has a modest effect on burden, interventions that limit reactivation have a greater impact on TB burden. Tools that make preventative therapy more feasible on a large scale and in elders will help China achieve the global targets.
authors.affiliation: Institute for Disease Modeling, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. ghuynh@intven.com.
authors.forename: Grace H
authors.initials: GH
authors.lastname: Huynh
authors.affiliation: Institute for Disease Modeling, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. dklein@intven.com.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Klein
authors.affiliation: China Office, The Bill & Melinda Gates Foundation, Beijing, 100027, China. daniel.chin@gatesfoundation.org.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Chin
authors.affiliation: Institute for Disease Modeling, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. bwagner@intven.com.
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Wagner
authors.affiliation: Institute for Disease Modeling, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. peckhoff@intven.com.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Eckhoff
authors.affiliation: Chinese Center for Disease Control and Prevention, Beijing, 102206, China. sdlirenzhong@163.com.
authors.forename: Renzhong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Chinese Center for Disease Control and Prevention, Beijing, 102206, China. wanglx@chinatb.org.
authors.forename: Lixia
authors.initials: L
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002681:China / Q000453:epidemiology; D023801:Directly Observed Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D015995:Prevalence; D016896:Treatment Outcome; D014376:Tuberculosis / Q000453:epidemiology* / Q000517:prevention & control* / Q000635:transmission; D014944:World Health Organization; D055815:Young Adult