A data-driven model for the assessment of Tuberculosis transmission in evolving demographic structures

Arregui, Sergio; Mj, Iglesias; Samper, Sofía; Marinova, Dessislava; Martin, Coralie; Sanz, Joaquín; Moreno, Yamir

doi:10.1101/112409

Cited by 1 publication

(5 citation statements)

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“…These results build on the study by Huynh and colleagues, 5 which showed the importance of controlling reactivation disease in people aged 65 years or older. Our results extend previous studies that suggested that adolescent and adult campaigns would have a greater benefit than infant vaccination, 13,15,20 and we develop the argument further by showing that in an epidemic in an ageing population, the greatest benefit could be achieved by targeting older adults, potentially minimising the resources required per case averted.…”

Section: Discussionsupporting

confidence: 86%

“…Infant vaccination could be explored, but the impact would be very low over this time period given the decreasing force of infection in China. 13,15 To answer the research question, we deliberately restricted mass campaigns to narrow age ranges (15-19 years and 60-64 years). If a new efficacious vaccine became available, broader campaigns could be implemented to increase overall benefits but would not affect our overall conclusions.…”

Section: Discussionmentioning

confidence: 99%

“…Mathematical modelling provides a systematic framework to explore the potential future impact of vaccine characteristics and implementation strategies to inform target product profile development. The impact achieved might vary by epidemiological and demographic setting, 12,13 therefore country-specific models are needed for appropriate vaccine selection and implementation planning, including age targeting. A phase 3 clinical trial of a prophylactic tuberculosis vaccine candidate has been conducted in China (NCT01979900) and therefore, modelling to clarify the potential benefit of new tuberculosis vaccines and different implementation strategies in China is urgently needed.…”

Section: Introductionmentioning

confidence: 99%

“…Traditional vaccine development pathways focused on infant vaccination; however, in the past few years, there has been a shift towards adolescents and adults, 14 supported by insights from mathematical modelling. 13,15 Yet populations aged 60 years and older remain neglected in tuberculosis vaccine development pathways, despite high tuberculosis disease burden in older age groups in several countries with different levels of sociodemographic development. 16 Given the dramatic and ongoing population ageing in China, 17 and higher prevalence of latent infection in older populations, 18 a shift in burden to older age groups could be expected.…”

Section: Introductionmentioning

confidence: 99%

“…12 Dynamics of tuberculosis disease and demographics are intimately linked, and influence the effect of age-targeted interventions. 13 Only two studies have modelled new tuberculosis vaccines in China, 19,20 and neither accounted for age specificities in epidemiology or demographics. Furthermore, in these studies, vaccination was either at birth or all ages, and vaccine characteristics modelled were unclear or unrealistic (eg, 100% vaccine efficacy).…”

Section: Introductionmentioning

confidence: 99%

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Age-targeted tuberculosis vaccination in China and implications for vaccine development: a modelling study

Harris

Sumner

Knight

et al. 2019

The Lancet Global Health

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Background 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. Methods 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. Findings 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. Interpretation 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. Funding Aeras and UK MRC.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%