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Expert Q&A

Multidrug-Resistant TB: The Future of Treatment

Gay Bronson, Deputy Director, Research Division, discusses promising developments in better treatments for multidrug-resistant TB.

Vital Strategies

(Photo:  STREAM clinical staff at St. Peter’s Tuberculosis Specialized Hospital in Addis Ababa, Ethiopia.)

Can you comment on the scope of the problem of tuberculosis today?

Tuberculosis (TB) is a communicable disease caused by the bacillus Mycobacterium tuberculosis and is one of the top 10 causes of death worldwide, outranking HIV/AIDS.  An estimated 10 million people globally fell ill with TB in 2018 and an estimated 1.45 million people died, including 251,000 deaths among HIV-positive people.[1] While TB incidence has slowly declined in recent years, there is still a significant need to identify, treat, and prevent this disease.

What is drug-resistant tuberculosis and why is it such a challenge?

The United Nations has called for coordinated and intensive efforts to address the global crisis of antimicrobial resistance. Each year, there are more than 700,000 deaths due to drug-resistant infections.  As drug-resistant TB accounts for nearly one-third of these deaths, it is imperative to address the challenge of drug-resistant TB. Annually, there are an estimated 500,000 new cases of rifampin-resistant TB (RR-TB), including an estimated 380,000 cases of multidrug-resistant TB (MDR-TB). MDR-TB is characterized by resistance to two of the most effective anti-TB drugs. Globally, only 32% of people with RR/MDR-TB are diagnosed and enrolled in treatment. In addition, MDR-TB is challenging to treat, requiring an arduous treatment that is long and involves drugs that are toxic and expensive. This gap in diagnosis and treatment contributes to increased rates of drug-resistant TB in the community. The challenging treatment regimen also contributes to further drug resistance. Improving diagnosis and treatment rates for drug-resistant TB is therefore a critical public health challenge of our day. 

What are some of the biggest challenges to addressing the problem of drug-resistant tuberculosis?

Although improving, treatment options for drug-resistant TB remain challenging for patients and health systems, and this is reflected in the relatively poor outcomes for patients with MDR-TB with only 56% of patients treated successfully. Treatment regimens can last up to 18 months or longer and shorter regimens often include painful injections that can cause significant adverse events, including hearing loss and kidney damage. These challenges can cause patients to abandon or interrupt their treatment. New and effective shorter regimens have the potential to improve treatment completion rates and therefore represent an important focus in the global fight against MDR-TB.

Why is research important for addressing MDR-TB?

Better treatment regimens for MDR-TB are an urgent public health priority. However, policy change, such as the endorsement of new treatment regimens, has significant consequences for affected populations and national healthcare budgets. It is therefore imperative that those decisions are made based on highest-quality evidence, ideally from clinical trials.

Until quite recently, MDR-TB treatment regimens had remained unchanged for many years and no new drugs for MDR-TB had been approved for use. Thankfully, this began to change in 2012, when a number of clinical trials to evaluate new drugs and regimens for MDR-TB began. One of those studies— the STREAM clinical trial—is being implemented by Vital Strategies and partners, including The Union and the Medical Research Council Clinical Trials Unit at University College London. Stage 1 of STREAM generated high-quality evidence that played a significant role in the WHO’s endorsement of the use of a shorter standardized 9 – 11-month regimen for MDR-TB. This was welcome news for patients and health systems, as the shorter regimen reduces treatment time and the overall pill burden for patients (a reduction of about 60 percent). 

STREAM Stage 2 is now underway, and is evaluating an all-oral, regimen that contains one of the newest anti-TB drugs, bedaquiline. Bedaquiline was approved by the United States Food and Drug Administration in 2012 and was the first new medicine for TB in more than forty years. STREAM Stage 2 is also evaluating the comparative cost of the two regimens, for both patients and the health systems. The results of STREAM Stage 2 have the potential to play a significant role in new international guidelines for the treatment of MDR-TB. 

What is community engagement and why is it an essential component of TB research?

Community engagement (CE) is a vital part of all TB research.  It helps ensure that clinical research is relevant and acceptable to affected communities and can improve trial implementation and participant outcomes by building a relationship of trust between affected communities and trial implementers. In the STREAM trial, community engagement is coordinated by 13 community advisory boards (CABs) comprised of community members and supported by the trial. The STREAM CABs play an important role in raising awareness of TB and the trial, while making complex information accessible to affected communities. They also help ensure those most affected by research are involved in all stages of the research process—from setting the research agenda through to advocating for policy change based on trial results.

How does Vital Strategies’ work contribute to addressing the challenge of MDR-TB?

Vital Strategies is proud to be among the organizations working to identify better treatments for MDR-TB and is thankful to USAID for its commitment to funding that work.  The evidence produced by Stage 1 of STREAM has played a major role in changing treatment guidelines and was published in The New England Journal of Medicine.  In addition, Vital Strategies’ work is fueling sustainable change in the countries where it works, in particular by building local capacity to diagnose, treat and research MDR-TB. Vital Strategies’ technical assistance programs help ensure that healthcare professionals in high burden settings have access to international TB experts and the latest innovations in diagnosis and treatment. In addition, we and our partners train clinicians, laboratory scientists, pharmacists and community advisory boards at STREAM sites on topics ranging from ICH Good Clinical Practice guidelines, to microbiological testing methods (LPA, FDA vital staining, etc.), to the ethics of community engagement and Good Participatory Practices for TB trials. Separately, Vital Strategies has trained hundreds of healthcare professionals in Asia, Africa and Latin America to conduct operational research independently, helping to ensure that routinely collected program data are used to continuously improve implementation of national TB programs in high-burden settings. We are hopeful these contributions will have a lasting, positive impact.

[1]               Global tuberculosis report 2019. Geneva: World Health Organization; 2019. License: CC BY-NC-SA 3.0 IGO