Ending tuberculosis: we can get there with a new roadmap

Two recent events have nudged tuberculosis, the leading infectious cause of death around the word, onto the world stage. The first was the World Health Organization’s Global Ministerial Conference on Ending TB, which was held in Moscow in 2017. The second was the United Nations High Level Meeting on tuberculosis in September 2018. At that seminal gathering of national leaders, a political declaration laid out two goals to achieve by 2022: prevent at least 30 million people from becoming ill with TB, and successfully treating 40 million people who are already infected with the disease.

That’s an audacious goal, especially given the fact that most of the tools currently available to prevent, treat, and cure TB are decades old and inadequate. For example, the only licensed TB vaccine, Bacille Calmette-Guerin (better known as BCG), is almost 100 years old and is primarily recommended for infants and children living in countries where TB is endemic. It is not effective in preventing adult pulmonary TB, which is the major transmissible form of the disease. Current treatment regimens are complicated and lengthy, with suboptimal cure rates.

Modernizing the TB “toolbox” is essential to the success of this roadmap. The WHO has approved a diagnostic tool to rapidly identify individuals with multi-drug resistant TB, and has also recommended a shorter, all-oral treatment regimen for this type of TB. On the research front, two candidate vaccines against TB have shown significant promise in mid-stage clinical trials.

That’s a good start, but more work is needed.

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The Lancet Commission on tuberculosis, which was established in 2017, has highlighted five priorities for the international community to accelerate progress against TB:

• ensure that all individuals receiving care for TB are provided high-quality rapid diagnostics and treatment wherever they seek care
• reach people and populations at high risk for TB (such as close contacts of people with active TB, and individuals with HIV, who are at high risk for developing TB) and bring them into care, both to find and treat previously undiagnosed cases and to prevent infection in those at high risk
• increase investment to accelerate TB research and development and quickly bring transformative diagnostics, therapeutic strategies, and vaccines into clinical practice
• make investment in TB programs a shared responsibility among donor countries and low and mid-income countries with high TB burdens by increasing TB-specific development assistance according to the individual financial needs of low- and middle-income countries
• hold countries and stakeholders accountable for progress made toward ending TB.

The Lancet Commission estimates that TB research and development will require an increase in global funding from its 2017 level of $772 million per year to at least $2 billion per year during the next four years to develop and produce an essential set of modernized TB-fighting tools. The United States government already provides 39 percent of all TB research and development funding and, with the Gates Foundation, provides 54 percent of the total funding for TB research and development.

The price of inaction by the international community, in terms of TB deaths and economic costs, will be enormous. For example, even with the best-case implementation of existing interventions, TB deaths would cost the economy of India $32 billion each year over the next 30 years. Although the commission calls for greater research and development investment from high-income countries, increasing contributions from high-burden middle-income countries, such as Brazil, China, India, Russia, and South Africa, are also needed to truly transform the global TB research and development agenda.

A comprehensive, multi-disciplinary strategic research agenda is essential to answering key questions concerning the pathogenesis of Mycobacterium tuberculosis, the bacterium that causes TB, and its interactions with the human immune system. In this regard, the 2018 Strategic Plan for TB Research from our organization, the U.S. National Institute of Allergy and Infectious Diseases, delineates the key basic and clinical scientific priorities that need to be addressed to rapidly advance the development of diagnostics, therapies, and vaccines against this pathogen.

Findings from basic and clinical biomedical research will inform the development of new and improved strategies to diagnose, prevent, and treat TB in children, adolescents, and adults, including individuals with HIV or other coinfections and comorbidities. Improving our understanding of how M. tuberculosis causes TB and identifying what triggers a latent infection to become active are keys to developing new evidence-based biomedical approaches to prevent and treat the disease.

State-of-the-art, point-of-care tools to rapidly diagnose the infection are essential to identify drug-sensitive, multi-drug resistant, and extensively drug-resistant TB to ensure that individuals are provided with appropriate TB therapeutic regimens and care.

The development of safe, effective, patient-friendly, and less-toxic treatment regimens for TB and multi-drug resistant TB are essential, especially low- and middle-income countries with high burdens of the disease.

We must accelerate the development and testing of vaccine and drug candidates to prevent the initial acquisition of TB infection, the establishment of latent TB infection, and its progression to active TB.

Many challenges will be faced in developing these new tools to be used in all populations, including adults, children, and individuals with HIV. Increased global investments in TB research and development are critical if we are to successfully meet these challenges.

To overcome the current gap in translating research findings into real-world settings, implementation science plays a vital role. Implementation science evaluates how promising new approaches perform in different settings and helps researchers refine and improve these approaches to meet the unique personal and societal needs of each population and subpopulation, especially in high-burden geographic and demographic areas.

Implementing new TB prevention interventions and treatment strategies requires improved coordination and cooperation among local public and private health care providers, clinics, public health departments, and ministries of health with the communities they serve.

The Lancet Commission has set the goal of achieving a TB-free world within a generation. That will require an intense and concentrated effort at all levels: local, regional, national, and global. The international commitment to successfully reach this goal is resounding in the political declaration of the United Nations High Level Meeting and the Lancet Commission’s “Building a tuberculosis-free world” report. By strengthening collaborative efforts among partners in communities, academia, industry, government, and public health, we can move from an aspirational goal to realistic advances that ameliorate the devastating suffering and economic costs of TB.

The pathway to ending TB — a disease that is preventable, treatable, and curable — is clear. But the time to act is now.

Robert W. Eisinger, M.D., is special assistant for acientific projects in the Office of the Director at the National Institute of Allergy and Infectious Diseases. Anthony S. Fauci, M.D., is the director of the National Institute of Allergy and Infectious Diseases.