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

BackgroundTuberculosis is a leading infectious cause of death worldwide. Novel vaccines will be required to reach global targets and reverse setbacks resulting from the COVID-19 pandemic. We estimated the impact of novel tuberculosis vaccines in low-income and middle-income countries (LMICs) in several delivery scenarios.MethodsWe calibrated a tuberculosis model to 105 LMICs (accounting for 93% of global incidence). Vaccine scenarios were implemented as the base-case (routine vaccination of those aged 9 years and one-off vaccination for those aged 10 years and older, with country-specific introduction between 2028 and 2047, and 5-year scale-up to target coverage); accelerated scale-up similar to the base-case, but with all countries introducing vaccines in 2025, with instant scale-up; and routine-only (similar to the base-case, but including routine vaccination only). Vaccines were assumed to protect against disease for 10 years, with 50% efficacy.FindingsThe base-case scenario would prevent 44·0 million (95% uncertainty range 37·2–51·6) tuberculosis cases and 5·0 million (4·6–5·4) tuberculosis deaths before 2050, compared with equivalent estimates of cases and deaths that would be predicted to occur before 2050 with no new vaccine introduction (the baseline scenario). The accelerated scale-up scenario would prevent 65·5 million (55·6–76·0) cases and 7·9 million (7·3–8·5) deaths before 2050, relative to baseline. The routine-only scenario would prevent 8·8 million (95% uncertainty range 7·6–10·1) cases and 1·1 million (0·9–1·2) deaths before 2050, relative to baseline.InterpretationOur results suggest novel tuberculosis vaccines could have substantial impact, which will vary depending on delivery strategy. Including a one-off vaccination campaign will be crucial for rapid impact. Accelerated introduction—at a pace similar to that seen for COVID-19 vaccines—would increase the number of lives saved before 2050 by around 60%. Investment is required to support vaccine development, manufacturing, prompt introduction, and scale-up

The cost and cost-effectiveness of novel tuberculosis vaccines in low- and middle-income countries: A modeling study.

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 1× 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$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

WHO global research priorities for antimicrobial resistance in human health.

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

The Eosinophil Regulates Immunity To The Parasitic Nematode Trichinella Spiralis

Parasitic diseases pose a significant burden on the health of millions of people. Chronic helminth infections are typified by enhanced Th2 responses. Understanding how Th2 immunity is regulated is important for developing effective treatments for parasitic diseases and other Th2 disorders. Infection of mice with Trichinella spiralis is an especially useful model system to study the development of Th2 immunity to a natural pathogen. Eosinophilia is a prominent feature of T. spiralis infection, and we have shown previously that in eosinophilablated, transgenic mice, T. spiralis larvae die in large numbers in the muscle. Death is promoted by inducible nitric oxide synthase (iNOS). Neutrophils and F4/80+ CD11b+ Ly6C+ macrophages produced iNOS. Compared to fully developed muscle larvae, growing larvae were more susceptible to NO mediated killing in vitro. Larval growth was impaired in eosinophil-ablated mice, potentially extending the period of susceptibility to NO mediated killing. These changes were associated with reduced numbers of Th2 cells in infected muscle. Reduction in Th2 cell number was not caused by poor recruitment, but rather by impaired Th2 cell production in draining lymph nodes. Adding back eosinophils into [DELTA]dblGATA recipients improved parasite growth and survival, as well as Th2 cell accumulation, supporting the role of the eosinophil in parasite retention and local immune regulation. i The influence of Th2 immunity on parasite growth was tested using mice deficient in STAT6 and IL-13. The results reveal that the IL-4/STAT6 axis is a key pathway that regulates parasite growth. Transcription of genes associated with nutrient deprivation was increased in muscles of infected eosinophil-deficient mice, but glycogen content of muscle larvae and muscle tissue was not altered by eosinophil deficiency. Taken together, the results show that eosinophils and STAT6 promote parasite establishment in the muscle by promoting larval growth while coincidentally inhibiting the Th1 immune response. i

A bibliometric analysis of tuberculosis research, 2007-2016.

BACKGROUND:Tuberculosis (TB) research is a key component of the End TB Strategy. To track research output, we conducted a bibliometric analysis of TB research from the past decade. METHODS:The Web of Science database was searched for publications from January 2007 to December 2016 with "tuberculosis" in the title. References were analysed using the R bibliometrix package. A year-stratified 5% random subset was drawn to extract funding sources and identify research areas. FINDINGS:The annual growth rate of publications was 7.3%, and was highest (13.1%) among Brazil, Russia, India, China and South Africa (BRICS). The USA was the most productive country, with 18.4% of references, followed by India (9.7%), China (7.3%), England (6.5%), and South Africa (3.9%). In the subset analysis, the most common research area was 'fundamental research' (33.8%). Frequently acknowledged funders were US and EU-based, with China and India emerging as top funders. Collaborations appeared more frequently between high-income countries and low/medium income countries (LMICs), with fewer collaborations among LMICs. CONCLUSION:The past decade has seen a continued increase in TB publications. While USA continues to dominate research output and funding, BRICS countries have emerged as major research producers and funders. Collaborations among BRICS would enhance future TB research productivity

Top ten journals most commonly published in over the period 2007–2016 and 5-year impact factor.

<p>Top ten journals most commonly published in over the period 2007–2016 and 5-year impact factor.</p

Flow chart of the bibliometric and subset analysis.

<p>Flow chart of the bibliometric and subset analysis.</p

Top ten publishing countries in TB research, 2007–2016.

<p>Top ten publishing countries in TB research, 2007–2016.</p

International collaborations in TB research.

<p>Each diagram includes the top five publishing countries for that year. Each line between countries represents an article with an author from each country. Dense regions of each plot indicate numerous collaborations between the two countries, demonstrating that collaborations have increased throughout the decade.</p