Matteo Zignol

The 2018 United Nations High-Level Meeting on Tuberculosis (UNHLM) set targets for case detection and TB preventive treatment (TPT) by 2022. However, by the start of 2022, about 13.7 million TB patients still needed to be detected and treated, and 21.8 million household contacts needed to be given TPT globally. To inform future target setting, we examined how the 2018 UNHLM targets could have been achieved using WHO-recommended interventions for TB detection and TPT in 33 high-TB burden countries in the final year of the period covered by the UNHLM targets. We used OneHealth-TIME model outputs combined with the unit cost of interventions to derive the total costs of health services. Our model estimated that, in order to achieve UNHLM targets, >45 million people attending health facilities with symptoms would have needed to be evaluated for TB. An additional 23.1 million people with HIV, 19.4 million household TB contacts, and 303 million individuals from high-risk groups would have required systematic screening for TB. The estimated total costs amounted to ~USD 6.7 billion, of which ~15% was required for passive case finding, ~10% for screening people with HIV, ~4% for screening household contacts, ~65% for screening other risk groups, and ~6% for providing TPT to household contacts. Significant mobilization of additional domestic and international investments in TB healthcare services will be needed to reach such targets in the future.

Most individuals who develop tuberculosis (TB) are working-age adults living in low- and middle-income countries (LMICs). The resulting disability and death impacts economic productivity and burdens health systems. New TB vaccine candidates may reduce this burden. In this study, we estimated the impact of introducing novel TB vaccines on GDP growth in 105 LMICs, using a macroeconomic model to simulate country-level GDP trends between 2020 and 2080, in 2020 USD. We compared scenarios for introduction of infant and adolescent/adult vaccine candidates to a no-new-vaccine counterfactual. Compared to the no-new-vaccine counterfactual, both vaccination scenarios produced greater cumulative GDP in the modelled countries over the study period, equivalent to $1.6 (95% uncertainty interval: $0.8–3.0) trillion for the adolescent/adult vaccine, and $0.2 ($0.1–0.4) trillion for the infant vaccine. These GDP gains were substantially lagged relative to the time of vaccine introduction, and concentrated in countries with higher current TB incidence.

Background One in two patients developing tuberculosis (TB) in low- and middle-income countries (LMICs) faces catastrophic household costs. We assessed the potential financial risk protection from introducing novel TB vaccines, and how health and economic benefits would be distributed across income quintiles. Methods We modelled the impact of introducing TB vaccines meeting the WHO preferred product characteristics in 105 LMICs. For each country, we assessed the distribution of health gains, patient costs, and household financial vulnerability following introduction of an infant vaccine, and separately for an adolescent/adult vaccine, compared to a ‘no-new-vaccine’ counterfactual. Patient-incurred direct and indirect costs of TB disease exceeding 20% of annual household income were defined as catastrophic. Findings Over 2028–2050, the health gains resulting from vaccine introduction were greatest in lower income quintiles, with the poorest two quintiles in each country accounting for 56% of total LMIC TB cases averted. Over this period, the infant vaccine was estimated to avert $5·9 (95% uncertainty interval: $5·3–6·5) billion in patient-incurred total costs, and the adolescent/adult vaccine was estimated to avert $38·9 ($36·6–41·5) billion. Over this period, 3·7 (3·3–4·1) million fewer households were projected to face catastrophic costs with the infant vaccine, and 22·9 (21·4–24·5) million with the adolescent/adult vaccine, with 66% of these gains accruing in the poorest two income quintiles. Interpretation Under a range of assumptions, introducing novel TB vaccines would reduce income-based inequalities in the health and household economic outcomes of TB in LMICs. Funding World Health Organization (2020/985800-0) Evidence before this study We searched MEDLINE using the terms “tuberculosis,” “catastrophic cost*,” and “vaccin*” and failed to find any original research articles that estimated the impact of TB vaccination on catastrophic costs incurred by TB patients. Previous studies have shown that improved TB prevention and care can lower patient costs and reduce the number of TB-affected households experiencing catastrophic costs, and previous modelling has estimated the potential impact of TB vaccination on patient costs in country case-studies. Survey evidence from high-burden countries have consistently demonstrated higher disease burden among poorer individuals, with TB prevalence in the lowest income quintile on average 2·3 times greater than estimated for the highest income quintile. TB patient cost surveys in high-burden countries have shown that TB patients experience high out-of-pocket and indirect costs, and that these costs represent a greater share of annual household income in poorer income quintiles. Added value of this study This is the first study to examine the potential for new vaccines to reduce the number of households experiencing catastrophic costs due to TB, and how both these benefits and health gains are distributed across income quintiles. Across all modelled countries over 2028–2050, an adolescent/adult vaccine was projected to reduce TB incidence in the poorest quintile by 13·3 (10·9–15·8) million (30% of total TB cases averted) and reduce the number of households experiencing catastrophic costs by 9·2 (7·5–11·0) million in the poorest quintile (40% of total cases of catastrophic costs averted) compared to the no-new-vaccination baseline. Implications of all the available evidence Under a range of assumptions, new TB vaccines could be highly impactful and help narrow income-based disparities in the health and the economic consequences of TB for low- and middle-income countries.

Background: Tuberculosis (TB) is preventable and curable but eliminating it has proven challenging. Safe and effective TB vaccines that can rapidly reduce disease burden are essential for achieving TB elimination. We assessed future costs, cost-savings, and cost-effectiveness of introducing novel TB vaccines in low- and middle-income countries (LMICs) for a range of product characteristics and delivery strategies. Methods and Findings: We developed a system of epidemiological and economic models, calibrated to demographic, epidemiological, and health service data in 105 LMICs. For each country, we assessed the likely future course of TB-related outcomes under several vaccine introduction scenarios, compared to a ‘no-new-vaccine’ counterfactual. Key economic inputs were derived from the Global Health Cost Consortium, WHO patient cost surveys, and the published literature. We estimated the incremental impact of vaccine introduction for a range of health and economic outcomes. In the base-case, we assumed a vaccine price of $4.60, and used a 1x per-capita GDP cost-effectiveness threshold (both varied in sensitivity analyses). Vaccine introduction was estimated to require substantial near-term resources, offset by future cost-savings from averted TB burden. From a health system perspective, adolescent/adult vaccination was cost-effective in 64 of 105 LMICs. From a societal perspective (including productivity gains and averted patient costs), adolescent/adult vaccination was projected to be cost-effective in 73 of 105 LMICs and cost-saving in 58 of 105 LMICs, including 96% of countries with higher TB burden. When considering the monetized value of health gains, we estimated that introduction of an adolescent/adult vaccine could produce $283–474 billion in economic benefits by 2050. Limited data availability required assumptions and extrapolations that may omit important country-level heterogeneity in epidemiology and costs. Conclusions: TB vaccination would be highly impactful and cost-effective in most LMICs. Further efforts are needed for future development, adoption, and implementation of novel TB vaccines. Funding: World Health Organization (2020/985800-0) Author summary: Why was this study done?: Previous studies have highlighted the economic impact of tuberculosis (TB) disease and mortality, and the potential economic impact that novel TB vaccines could have on reducing this burden in specific low- and middle-income countries (LMICs). The cost and cost-effectiveness of novel TB vaccines, which depend on vaccine price and delivery strategy that may vary by country, are needed by vaccine developers, manufacturers, and potential purchasers to guide investment decisions. No modelling studies have estimated the cost and cost-effectiveness of novel TB vaccine products with country-specific assumptions for medical and non-medical costs, indirect costs, vaccine delivery costs, and delivery strategies across a wide range of LMICs. What did the researchers do and find?: We estimated the costs, cost-effectiveness, and incremental net monetary benefit of TB vaccine introduction from both the health system and societal perspective, in order to inform global-level decision-making for novel TB vaccine investment and introduction. Using mathematical and economic models, we assessed scenarios for the introduction of novel TB vaccines with a wide range of characteristics and a diverse set of health and economic outcomes, including country-specific introduction years from 2028–2047. Our analysis projected that an effective new TB vaccine could offer large potential health and economic benefits over 2028–2050. From a societal perspective, vaccination was projected to be cost-effective in 74 LMICs compared to a 1x per-capita gross domestic product threshold. When considering the monetized value of health gains, we estimated that introduction of an adolescent/adult TB vaccine could produce $283–474 billion in health and economic benefits by 2050, with greater benefits in LMICs with elevated TB incidence. What do these findings mean?: Introduction of a new TB vaccine was found to be impactful and cost-effective for a range of assumptions on vaccine price and delivery strategies, with aggregate health and economic benefits of similar scale to the most influential health interventions in LMIC settings in recent years. The results of these analyses can be used by global and country stakeholders to inform TB vaccine policy and introduction preparedness, as well as decision-making around future development, adoption, and implementation of novel TB vaccines.

Background: Tuberculosis is a leading infectious cause of death worldwide. Novel vaccines will be required to reach global targets and reverse setbacks from the COVID-19 pandemic. We estimated the impact of novel tuberculosis vaccines in low- and middle-income countries (LMICs) under alternative delivery scenarios. Methods: We calibrated a tuberculosis model to 105 LMICs (93% of global tuberculosis incidence). Vaccine scenarios were implemented as Basecase : routine vaccination of 9-year-olds and a one-time vaccination campaign for ages ≥10 with country-specific introduction between 2028–2047 and 5-year scale-up to target coverage; Accelerated Scale-up : as Basecase , but all countries introducing in 2025 with instant scale-up; and Routine Only : as Basecase , but routine vaccination only. Vaccines protected against disease for 10-years, with 50% efficacy. Findings: The Basecase scenario prevented 44.0 (95% uncertainty range=37.2–51.6) million tuberculosis cases, and 5.0 (4.6–5.4) million tuberculosis deaths before 2050, including 2.2 million in the WHO South-East Asian region. The Accelerated Scale-up scenario prevented 65.5 (55.6–76.0) million cases and 7.9 (7.3–8.5) million deaths before 2050. The Routine Only scenario prevented 8.8 (7.6–10.1) million cases and 1.1 (0.9–1.2) million deaths before 2050. Interpretations: Novel tuberculosis vaccines could have substantial impact, which will vary depending on delivery strategy. Including a campaign will be crucial for rapid impact. Accelerated introduction, more similar to the pace of COVID-19 vaccines, could increase lives saved by around 60%. Investment is required to support vaccine development, manufacturing, prompt introduction and scale-up. Funding: WHO (2020/985800-0)