Reimagining the Research Approach to Tuberculosis

Abstract

Abstract.Controlling and ultimately ending tuberculosis (TB) as a public health scourge will require a multifaceted and comprehensive approach involving the intensification of public health efforts, including scaling-up the delivery of current diagnostic, preventive, and therapeutic tools. However, a critically important element in the effort to end TB is an accelerated biomedical research effort to address the many unanswered questions about the disease process itself and to develop improved and innovative countermeasures. An intensive effort toward these research goals will facilitate the achievement of the aspirational goal of ending TB.

The Pathogenesis of Tuberculosis: The Early Infiltrate of Post-primary (Adult Pulmonary) Tuberculosis: A Distinct Disease Entity

“…Our lack of understanding of these functions is still a major impediment to development of vaccines and new therapies ( 3 – 6 ). Dr. Anthony Fauci, Director of NIAID, expressed a nearly universal opinion with the statement: “We need to better understand the delicate balance between the host and pathogen in the context of the entire biological system and this requires a ‘radical and transformational approach.’ “Our goal should be to transform the entire field.” ( 7 , 8 ).…”

Building a tuberculosis-free world: The Lancet Commission on tuberculosis

“…292 Nonetheless, promising preclinical efforts exist that must be substantially expanded. These efforts include using computational modelling to better understand complex biological interactions between pathogen and host, 293 high-throughput host genomic screening to identify RNA signatures associated with the risk for disease, 294 and improved animal models of tuberculosis latency. 295 To accelerate the development pipelines for diagnostics, therapeutics, and chemopreventive strategies and vaccines, it is imperative to develop an integrated research strategy and agenda to close cross-cutting gaps in tuberculosis research and development ( figure 7, appendix p 48).…”

“…354 The investment in HIV research and development over the past two decades, leading to over 30 new drugs and numerous diagnostic and preventive technologies, provides compelling evidence for greater investment in tuberculosis research and development. 293 The Global Drug Facility (GDF), part of the Stop TB Partnership, serves an important function in marketshaping activities, using donor financing to consolidate demand from different countries to negotiate lower prices for tuberculosis drugs, attract additional suppliers, and incentivise innovation, in particular for more expensive second-line agents and paediatric medicines. [367][368][369] These kinds of activities will remain important as countries increasingly assume cofinancing responsibilities, transition out of donor eligibility, or both, as they might have difficulty negotiating lowest possible prices or accessing concessional prices for diagnostics.…”

Toward the Development of a Circulating Free DNA-BasedIn VitroDiagnostic Test for Infectious Diseases: a Review of Evidence for Tuberculosis

“…At the first World Health Organization Global Ministerial Conference on Ending Tuberculosis, Anthony Fauci and colleagues highlighted that “we need to think about TB in modern terms and use cutting-edge technologies,” in order to start thinking about ending TB (19). cfDNA-based tests have the potential to improve TB diagnosis and be a true “game-changer.” The intention of the manuscript is to (i) review the current evidence and potential of blood and urinary cfDNA as a biomarker for TB, and (ii) describe the main challenges for the development of an appropriate in vitro diagnostic (IVD) test for cfDNA-based TB detection for use in limited resource settings.…”