The impact of alternative delivery strategies for novel tuberculosis vaccines in low-income and middle-income countries: a modelling study

Clark, Rebecca A.; Mukandavire, Christinah; Portnoy, Allison; Weerasuriya, Chathika; Deol, Arminder K.; Scarponi, Danny; Iskauskas, Andrew; Bakker, Roel; Quaife, Matthew; Malhotra, Shelly; Gebreselassie, Nebiat; Zignol, Matteo; Hutubessy, Raymond; Giersing, Birgitte; Jit, Mark; Harris, Rebecca; Menzies, Nicolas A; White, Richard Grant

doi:10.1016/s2214-109x(23)00045-1

Cited by 22 publications

(52 citation statements)

References 21 publications

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“…We adapted previous models and developed a compartmental dynamic model of tuberculosis in India. 5,11,20 Our model was stratified by tuberculosis natural history and treatment, differences in access-to-care, vaccination, and age. We represented tuberculosis natural history by allowing for Mtb infection along a spectrum from uninfected to active clinical disease.…”

Section: Methodsmentioning

confidence: 99%

“…4 The National Strategic Plan also calls for further development in tuberculosis vaccines, which has been a high priority for global organisations such as the World Health Organization (WHO). A recently completed WHO-commissioned study assessing the full value of tuberculosis vaccines made a strong case from the health and economic perspectives for continued investment, [5][6][7][8][9] and previous work has demonstrated that novel vaccines or vaccination strategies will be needed to eliminate tuberculosis. 10,11 Currently, sixteen candidates are in various phases throughout the vaccine pipeline, being trialled in a variety of ages and spanning prevention of disease, infection, and recurrence endpoints.…”

Section: Introductionmentioning

confidence: 99%

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New tuberculosis vaccines in India: Modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01_Eand BCG-revaccination

Clark

Weerasuriya

Portnoy³

et al. 2023

Preprint

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Background India had an estimated 2.9 million tuberculosis cases and 506 thousand deaths in 2021. Novel vaccines effective in adolescents and adults could reduce this burden. M72/AS01E and BCG-revaccination have recently completed Phase IIb trials and estimates of their population-level impact are needed. We estimated the potential health and economic impact of M72/AS01E and BCG-revaccination in India and investigated the impact of variation in vaccine characteristics and delivery strategies. Methods We developed an age-stratified compartmental tuberculosis transmission model for India calibrated to country-specific epidemiology. We projected current trends to 2050 assuming no-new-vaccine introduction, and M72/AS01E and BCG-revaccination scenarios over 2025-2050 exploring uncertainty in product characteristics and implementation. We estimated reductions in tuberculosis cases and deaths by each scenario compared to no-new-vaccine introduction, as well as costs and cost-effectiveness from health-system and societal perspectives. Results M72/AS01E scenarios were predicted to avert 40% more tuberculosis cases and deaths by 2050 compared to BCG-revaccination scenarios. Cost-effectiveness ratios for M72/AS01E vaccines were around seven times higher than BCG-revaccination, but nearly all scenarios were cost-effective. The estimated average incremental cost was US$190 million for M72/AS01E and US$23 million for BCG-revaccination per year. Sources of uncertainty included whether M72/AS01E was efficacious in uninfected individuals at vaccination, and if BCG-revaccination could prevent disease. Conclusions M72/AS01E and BCG-revaccination could be impactful and cost-effective in India. However, there is great uncertainty in impact, especially with varying vaccine characteristics. Greater investment in vaccine development and delivery is needed to raise the probability of success.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New tuberculosis vaccines in India: Modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01_Eand BCG-revaccination

Clark

Weerasuriya

Portnoy³

et al. 2023

Preprint

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“…Mathematical models have been used extensively to estimate the potential impact and cost-effectiveness of tuberculosis vaccines with different specifications [6]. Models have, for example, provided age indications for TB vaccines, by demonstrating the greater and more rapid impact before 2050 of targeting adolescents and adults instead of infants in low and middle income countries [7], [8], and older adults only in settings such as China [9]. Models have also assessed whether greater population-level impact would be delivered by vaccines with efficacy in Mycobacterium tuberculosis (Mtb)-infected populations (often referred to as current infection vaccines) versus uninfected populations (often referred to as no current infection vaccines) [7], [8], [10]- [12],…”

Section: Introductionmentioning

confidence: 99%

“…and how population-level impact may vary by age and setting [10]. Model results such as these are being used to guide the development and implementation planning of new vaccines, informing, for example, the design of future clinical trials [7], [8], [13].…”

Section: Introductionmentioning

confidence: 99%

Is neglect of self-clearance biassing TB vaccine impact estimates?

Scarponi

Clark

Weerasuriya

et al. 2023

Preprint

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Background. Mathematical modelling has been used extensively to estimate the potential impact of new tuberculosis vaccines, with the majority of existing models assuming that individuals with Mycobacterium tuberculosis (Mtb) infection remain at lifelong risk of tuberculosis disease. Recent research provides evidence that self-clearance of Mtb infection may be common, which may affect the potential impact of new vaccines that only take in infected or uninfected individuals. We explored how the inclusion of self-clearance in models of tuberculosis affects the estimates of vaccine impact in China and India. Methods. We calibrated a tuberculosis model to a scenario without self-clearance and to various scenarios with self-clearance. To account for the current uncertainty in self-clearance properties, we varied the rate of self-clearance, and the level of protection against reinfection in self-cleared individuals. We introduced potential new vaccines in 2025, exploring vaccines that work in uninfected or infected individuals only, or that are effective regardless of infection status, and modelling scenarios with different levels of vaccine efficacy in self-cleared individuals. We then estimated the relative incidence reduction in 2050 for each vaccine compared to the no vaccination scenario. Findings. The inclusion of self-clearance increased the estimated relative reductions in incidence in 2050 for vaccines effective only in uninfected individuals, by a maximum of 12% in China and 8% in India. The inclusion of self-clearance increased the estimated impact of vaccines only effective in infected individuals in some scenarios and decreased it in others, by a maximum of 14% in China and 15% in India. As would be expected, the inclusion of self-clearance had minimal impact on estimated reductions in incidence for vaccines that work regardless of infection status. Interpretations. Our work suggests that the neglect of self-clearance in mathematical models of tuberculosis vaccines does not result in substantially biassed estimates of tuberculosis vaccine impact. It may, however, mean that we are slightly underestimating the relative advantages of vaccines that work in uninfected individuals only compared to those that work in infected individuals.

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“…Considering these developments, Clark and colleagues 7 conducted a modelling study to explore implementation strategies for an effective tuberculosis vaccine to all age groups. The outcome was measured by death and disease averted by 2050 in 105 lower-income and middle-income countries (LMICs).…”

mentioning

confidence: 99%

Planning to introduce novel tuberculosis vaccines in high burden settings: how could this be done?

Cotton¹,

Rabie²

2023

The Lancet Global Health

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The impact of alternative delivery strategies for novel tuberculosis vaccines in low-income and middle-income countries: a modelling study

Cited by 22 publications

References 21 publications

New tuberculosis vaccines in India: Modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01_Eand BCG-revaccination

New tuberculosis vaccines in India: Modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01_Eand BCG-revaccination

Is neglect of self-clearance biassing TB vaccine impact estimates?

Planning to introduce novel tuberculosis vaccines in high burden settings: how could this be done?

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The impact of alternative delivery strategies for novel tuberculosis vaccines in low-income and middle-income countries: a modelling study

Cited by 22 publications

References 21 publications

New tuberculosis vaccines in India: Modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01Eand BCG-revaccination

New tuberculosis vaccines in India: Modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01Eand BCG-revaccination

Is neglect of self-clearance biassing TB vaccine impact estimates?

Planning to introduce novel tuberculosis vaccines in high burden settings: how could this be done?

Contact Info

Product

Resources

About

New tuberculosis vaccines in India: Modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01_Eand BCG-revaccination

New tuberculosis vaccines in India: Modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01_Eand BCG-revaccination