Ask an Expert: Advances in Tuberculosis with Ken Castro

By Shelby Crosier

Every year, World Tuberculosis (TB) Day is observed on March 24 to bring awareness to the disease, which every year sickens 10 million people and causes 1.5 million deaths. Over 80% of both TB cases and TB deaths happen in low- and middle-income countries.

Ken Castro, MD, is a professor of global health, epidemiology, and infectious diseases at Emory University’s Rollins School of Public Health and School of Medicine. He also serves as co-director of the Emory TB Center and associate director of the administrative core at the Emory/Georgia TB Research Advancement Center (TRAC). Here, Castro explains recent advancements in TB, exciting possibilities on the horizon, and how recent funding cuts could put worldwide TB prevention and treatment in jeopardy.

What is the research focus for the Emory TB Center and TRAC?

The multidisciplinary research being done at TRAC and the Emory TB Center spans basic Mycobacterium tuberculosis pathogenesis and host immunity to infection, large and small animal models, the role of co-morbidities (such as diabetes and malnutrition) and co-infections (such as HIV), molecular epidemiology and geospatial studies, patterns of disease transmission and the role of social networks, drivers of drug resistance, biomarker discovery, diagnostic development, and long-term pulmonary and cardiometabolic damage following TB treatment. There is interest in implementing vaccine safety and efficacy studies.

What advances have been made in TB treatment and prevention in recent years?

In recent years, the treatment of people with TB disease has advanced immensely through clinical trials that established the safety and efficacy of shorter treatment regimens for drug-susceptible TB, drug-resistant TB, and TB preventive therapy.

We have also made advances with access to pediatric drug formulations, the use of molecular tests for rapid diagnosis, and the use of molecular tests to identify drug resistance and inform the selection of optimal treatment regimens.

Other remarkable advances have been made in technology to assist with TB diagnosis and treatment:

• Deployment of ultraportable chest X-rays linked to computer-assisted A.I. readings to detect abnormalities in the lungs
• The use of mobile phones and wearable devices to promote treatment adherence, monitor for side effects, and ensure that people with TB infection or disease are cured.

There are also six vaccine candidates in the pipeline for clinical studies.

What challenges do we still face in TB treatment and prevention?

One challenge is that we do not fully understand the immune correlates of protection in ways that could accelerate targeted vaccine development.

It is also a challenge to bring to scale the implementation of the recent advances mentioned above. These require significant resource investments, a trained workforce, and community engagement—with a sustained long-term commitment.

The recent stop work orders by the U.S. government that have ceased foreign assistance through the U.S. Agency for International Development (USAID) have devastating effects in interrupting therapy, promoting drug resistance, worsening illness (and deaths), and contributing to ongoing TB transmission.

Tell me more about what could happen to the TB landscape without USAID funding.

There are a few major concerns:

• Program interruption: Programs could be dismantled in about 18 countries with a high burden of TB, mostly across Southeast Asia, the Western Pacific, and especially in Africa. Treatment disruptions and program stoppages could exponentially increase TB transmission rates and lead to a 28-32% increase in the number of people with TB. There could be similar increases in those with drug-resistant TB.
• Global Drug Facility budget cuts: All operating costs and 10% of the drug budget for the Global Drug Facility, the main supply channel for tuberculosis medications, come from USAID. Last year, this mechanism provided TB treatment to nearly 3 million people, including 300,000 children.
• Interruption of research: Smart4TB and TB Alliance are the two main research consortia working on prevention, diagnostics, and treatment for TB. There are severe adverse consequences to interrupting treatment for people in clinical trials; there is a risk of worsening disease, developing drug resistance, and death.

Already, funding constraints are leading to layoffs, supply chain breakdowns, and shuttered surveillance programs in TB-affected areas. A new webpage has been developed to keep track of the estimated impact associated with USAID’s funding freeze.

The Stop TB Partnership's Global Plan to End TB 2023-2030 has estimated an unacceptably high price of inaction in preventable suffering and deaths: an additional 43 million people with TB disease and 6.6 million deaths, with a global economic cost of $1 trillion.

What innovations in TB are on the horizon that excite you?

The ability to rapidly deploy existing advances to screen high-risk groups and establish same-day diagnosis and treatment initiation with community engagement to achieve a win-win scenario. Also, the implementation of infection prevention and control measures in crowded settings (such as prisons, shelters, and hospitals) and evaluating the safety and efficacy of newer vaccines could be "game-changers."