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

Abstract

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.

Survival Analysis of Risk Factors for Mortality in a Cohort of Patients with Tuberculosis

“…However, in the network reporting system of infectious diseases in China, the number of reported TB cases and deaths ranks high in the epidemiology of class A and class B infectious diseases. TB is the third leading cause of death among major infectious diseases and more than 70% of deaths among patients with TB occur in the first 2 months of TB treatment [ 4 , 5 ]. Therefore, it is important to explore the risk factors of TB death under the DOTS strategy.…”

The potential impact of COVID-19-related disruption on tuberculosis burden

“…However, our results suggest that the setting-specific nature of the TB epidemic and differences in changing social contacts and service delivery could create highly heterogeneous changes to long-term TB incidence. For example, higher proportions of TB resulting from reactivation in China [13] suggest that reductions in social contacts may have less influence on incidence than elsewhere. Further important factors for consideration include that health service declines are likely to have a greater impact on patients with drug-resistant TB (which we do not consider here).…”

Clinical Development of New TB Vaccines: Recent Advances and Next Steps

“…For example, prevalence of Mtb infection defined by positive IGRA in China was 3% in adolescents, rising to 33% in older adults, consistent with the epidemiology of an aging TB epidemic (Gao et al, 2015). It follows that a postexposure vaccination campaign for Mtb-infected people in China should target primarily older adults, an approach which has the maximum modeled population-level impact on the Chinese epidemic (Harris et al, 2019). By contrast, in South Africa, 49% of adolescents and 56% of adults were IGRA-positive (Bunyasi et al, 2019;Mahomed et al, 2006), consistent with a high rate of ongoing Mtb transmission to younger people.…”

“…The impact of vaccines that are efficacious in preexposure versus post-exposure approaches will be influenced by epidemiological setting and vaccine implementation. Determinants of impact include the relative contribution to TB disease burden from recent Mtb transmission versus reactivation, and the prevalence of Mtb infection in the vaccinated population, in particular when considering age-targeted vaccination of children or adolescents in whom Mtb infection prevalence is lower than in adult populations (Harris and White, 2018;Harris et al, 2019;Renardy and Kirschner, 2019). Modeling the impact and cost-effectiveness of M72/AS01 E vaccination would be the first step when considering feasibility and cost of roll-out.…”