Importance of tuberculosis vaccination targeting older people in China
Authors: Yue Wang, Weibing Wang
Journal: The Lancet Global Health (2019)

Given that existing tuberculosis interventions and strategies are not going to enable achievement of WHO's goal to eliminate tuberculosis by 2050,1Xu K Ding C Mangan CJ et al.Tuberculosis in China: A longitudinal predictive model of the general population and recommendations for achieving WHO goals.Respirology. 2017; 22: 1423-1429Crossref PubMed Scopus (11) Google Scholar better diagnostics, treatments, and innovative tools such as new tuberculosis vaccines are urgently needed. Although there have been rapid advances in tuberculosis vaccine clinical research over the past decade, mathematical modelling studies, which can provide a method to predict the potential future impact of vaccine, are still uncommon. In The Lancet Global Health, Rebecca Harris and colleagues2Harris RC Sumner T Knight GM et al.Age-targeted tuberculosis vaccination in China and implications for vaccine development: a modelling study.Lancet Glob Health. 2019; (published online Jan 7.)http://dx.doi.org/10.1016/S2214-109X(18)30452-2Summary Full Text Full Text PDF PubMed Scopus (29) Google Scholar pioneer a model to estimate the influence of age-targeted vaccination with varying vaccine characteristics in China. Their analysis provides a useful investigation of the potential impact of new tuberculosis vaccines targeted at older adults (60–64 years), and compares this approach to the strategic focus on adolescents (15–19 years). The main conclusion is that adolescent-targeted tuberculosis vaccines will have a low effect on tuberculosis incidence and mortality in ageing, reactivation-driven tuberculosis epidemics such as that in China, whereas an efficacious post-infection vaccine delivered to older adults will be crucial to maximise population-level effects. For example, in the intermediate vaccine profile (60% efficacy, 10-year protection, and 70% coverage), vaccination of older adults reduced median population-level incidence by up to 157·5 times (95% uncertainty interval 119·3–225·6) more than adolescent vaccination. Older adults should be included in tuberculosis vaccine clinical development and implementation planning. However, given its unique tuberculosis status, China should be cautious when interpreting Harris and colleagues' conclusion. First, this paper used the Chinese population as a target population. However, some of the parameters the authors input into the model were from other settings or a global average. For example, Harris and colleagues used probability of transmission per respiratory contact from the global literature; yet the scale of transmission of tuberculosis in the Chinese population is usually smaller than that from other regions. Although the authors argue that using clustering data to inform the transmission parameter would conflate transmission with other parameters (eg, contact patterns), clustering data still need to be considered. Additionally, contacts were defined as face-to-face conversations or skin-on-skin touch. However, unlike in other settings, previous reports show that in addition to close contact, occasional contact might also be important for tuberculosis transmission in China.3Wang W Hu Y Mathema B Jiang W Kreiswirth B Xu B Recent transmission of W-Beijing family Mycobacterium tuberculosis in rural eastern China.Int J Tuberc Lung Dis. 2012; 16: 306-311Crossref PubMed Scopus (14) Google Scholar, 4Yang C Luo T Shen X et al.Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigation.Lancet Infect Dis. 2017; 17: 275-284Summary Full Text Full Text PDF PubMed Scopus (139) Google Scholar The definition might have excluded a substantial proportion of secondary cases occurring from occasional contact. Second, China initiated its national tuberculosis programme in 1992 and achieved universal coverage of the programme in the proceeding few years. That fact means that most older patients with tuberculosis have not received standardised treatment during previous tuberculosis episodes, which might be the possible reason for the high reactivation rate5Leung CC Lam TH Chan WM et al.Diabetic control and risk of tuberculosis: a cohort study.Am J Epidemiol. 2008; 167: 1486-1494Crossref PubMed Scopus (207) Google Scholar and high incidence of multidrug-resistant and extensively drug-resistant tuberculosis. China's drug-resistant tuberculosis burden ranks second in the world and remains a serious barrier to tuberculosis elimination.6Global Tuberculosis Programme, WHOGlobal tuberculosis report. World Health Organization, Geneva, Switzerland2018https://www.who.int/tb/publications/global_report/en/Date accessed: September 18, 2018Google Scholar The Article's conclusion is based on the rising proportion of cases occurring from reactivation, but this proportion might decline in subsequent decades with the improvement of diagnostics and intervention strategies. The higher rate of relapse in older adults could also be partly due to historically poor tuberculosis treatment. Third, this Article mentioned that the number needed to vaccinate per case averted with older adult vaccination was lower than with adolescent vaccination and considered that cost-effectiveness calculations might also support older adult vaccination strategies. Considering the mechanism of the vaccines, the difference between vaccine efficacy for older adults and adolescents is uncertain. Therefore, people aged 65 years or older might be unable to achieve the same level of protection as an adolescent when vaccinated with an equivalent vaccine. Under such a premise, the question remains whether the standard intermediate vaccine profile mentioned in the Article can be achieved. Furthermore, gender differences were not considered in the modelling, but were reported to exist.7Rhines AS The role of sex differences in the prevalence and transmission of tuberculosis.Tuberculosis. 2013; 93: 104-107Summary Full Text Full Text PDF PubMed Scopus (51) Google Scholar Rural to urban migration is a substantial driving force of tuberculosis transmission and is a common cause in big cities in China. The scale of population movement and the potential different coverage of the vaccine might affect the tuberculosis epidemics on a large scale. Unfortunately, this study did not include population movement in the model, and thus might have underestimated the scale of transmission.8Yang C Lu L Warren JL et al.Internal migration and transmission dynamics of tuberculosis in Shanghai, China: an epidemiological, spatial, genomic analysis.Lancet Infect Dis. 2018; 18: 788-795Summary Full Text Full Text PDF PubMed Scopus (51) Google Scholar The global strategy in the treatment of tuberculosis in areas with a low incidence, such as China, is to conduct prophylactic treatment to prevent the reactivation of latent tuberculosis infection.9Ai JW Ruan QL Liu QH Zhang WH Updates on the risk factors for latent tuberculosis reactivation and their managements.Emerg Microbes Infect. 2016; 5: e10Crossref PubMed Scopus (33) Google Scholar The main results of this paper are also consistent with the conclusions of Dye and colleagues10Dye C Glaziou P Floyd K Raviglione M Prospects for tuberculosis elimination.Annu Rev Public Health. 2013; 34: 271-286Crossref PubMed Scopus (257) Google Scholar regarding the importance of post-infection vaccines in China. Future trends in policy and diagnosis and treatment strategies are unpredictable, and the cost-effectiveness of a new tuberculosis vaccine after its launch cannot be predicted with certainty. However, Harris and colleagues2Harris RC Sumner T Knight GM et al.Age-targeted tuberculosis vaccination in China and implications for vaccine development: a modelling study.Lancet Glob Health. 2019; (published online Jan 7.)http://dx.doi.org/10.1016/S2214-109X(18)30452-2Summary Full Text Full Text PDF PubMed Scopus (29) Google Scholar have proposed groundbreaking implications for vaccine development that can be built upon with future research. We declare no competing interests. Age-targeted tuberculosis vaccination in China and implications for vaccine development: a modelling studyAdolescent-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. Full-Text PDF Open Access