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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. Vaccine scenarios considered 2 vaccine product profiles (1 targeted at infants, 1 at adolescents/adults), both assumed to prevent progression to active TB. Key economic inputs were derived from the Global Health Cost Consortium, World Health Organization (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 gross domestic product (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 to 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., Author(s): Allison Portnoy 1,*, Rebecca A. Clark 2,3,4, Matthew Quaife 2,3,4, Chathika K. Weerasuriya 2,3,4, Christinah Mukandavire 2,3,4, Roel Bakker 2,3,4,5, Arminder K. Deol 2,3,4,6, Shelly Malhotra 7,8, Nebiat Gebreselassie [...]

Background To appropriately treat tuberculosis (TB) with regimens that combine novel and older drugs, evidence-based, context-specific strategies for drug-susceptibility testing (DST) will be required. Methods We created a Markov state-transition model of 100 000 adults with TB receiving a novel, fluoroquinolone (FQ)–containing regimen. We estimated clinical outcomes and resource utilization with no FQ-DST, universal FQ-DST, or FQ-DST only for patients with rifampin-resistant TB ("targeted FQ-DST"). We considered scenarios of stronger (South Africa) and weaker (Southeast Asia) correlation of fluoroquinolone resistance with rifampin resistance, with sensitivity analysis for other setting and regimen characteristics. Results Relative to no FQ-DST, targeted FQ-DST increased cure of FQ-resistant TB by 7.5% (interquartile range [IQR], 6.7%–9.2%) in South Africa and 1.7% (IQR, 0.7%–2.5%) in Southeast Asia. However, rare FQ resistance among the more prevalent rifampin-susceptible TB accounted for 50% of FQ-resistant TB in South Africa and 83% in Southeast Asia. As a result, universal FQ-DST further increased cure of FQ-resistant TB by 3.4% (IQR, 2.3%–5.4%) in South Africa and 5.8% (IQR, 5.1%–6.3%) in Southeast Asia. With targeted FQ-DST, 1 additional patient was cured per 50 (IQR, 42–70) tests in South Africa and 44 (IQR, 37–51) in Southeast Asia. When expanding from targeted to universal FQ-DST, 1 additional cure required 3500 (IQR, 2300–5500) tests in South Africa and 410 (IQR, 370–450) in Southeast Asia. Conclusions FQ-DST improved patient outcomes and was particularly important for high-risk patient groups and less robust regimens. A universal strategy was favored in generalized epidemics of fluoroquinolone resistance. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs) are revolutionizing management of non-communicable diseases in high-income countries and are increasingly being advanced for a range of infectious diseases (IDs). However, access to existing mAbs is limited in low- and middle-income countries (LMICs), and investment in developing fit-for-purpose mAbs for IDs that disproportionately affect LMICs has been limited. Underlying these access barriers are systemic challenges, including a lack of commercial incentives to target LMIC markets and complexity in manufacturing and regulatory processes. Novel strategies are needed to overcome systemic access barriers for mAbs. We outline key areas where new approaches could address these barriers, based on a multistakeholder consultation in March 2023. Three disease-market archetypes are identified to guide thinking about business models tailored to different contexts. New business models are needed to incentivize development and manufacturing of ID mAbs and to ensure mAbs are optimized with a target product profile and cost of goods that enable use in diverse LMIC settings. Lessons can be applied from voluntary licensing strategies and product development partnerships that have shown success in catalysing development and affordable supply for a range of infectious diseases. Technology transfer will be key to expand LMIC research and manufacturing capacity and to enable sustainable and diversified supply. Improved market intelligence, demand aggregation mechanisms, and portfolio-based manufacturing models could be used to de-risk commercial investment and establish a sustainable manufacturing ecosystem for affordable mAbs. Novel regulatory approaches and robust technology transfer may reduce data requirements and timelines for biosimilar approvals. Trailblazer products, with coordinated "end-to-end" support from funders, can demonstrate proof of concept for pathways to accessible mAbs across a broader range of LMICs. Research funders; local, regional, global health agencies; and, private sector partners should commit to implementing innovative partnerships and end-to-end strategies that enable equitable access to mAbs for infectious diseases in LMICs., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests. Shelly Malhotra is an employee of IAVI, a non-profit product development partnership whose portfolio includes mAb products. Esteban Burrone and Sébastien Morin are employees of the Medicines Patent Pool, an organization involved in supporting access to novel medicines (including mAbs) through voluntary licensing and technology transfer. Anne-Isabelle Cameron, Cherise P Scott and Carmen Pérez-Casas are employees of Unitaid, a global health agency that supports equitable access to health products, including mAbs, in low- and middle-income countries. Dzintars Gotham has received consultancy fees from Unitaid and the Medicines Patent Pool. Peter J. Gardner and Colleen Loynachan are employees of Wellcome, a philanthropic foundation that supports projects to expand access to mAbs in low- and middle-income countries, (Copyright: © 2024 Malhotra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)