Improved Tuberculosis Tests and Treatments are Vital to Overcoming Drug Resistance
Older highly drug-resistant TB treatment (above) compared with new BPaL regimen (below).

In the face of the COVID-19 pandemic, tuberculosis mortality has started to increase for the first time in a decade. In 2020 alone, more than 1.5 million people died from TB. Every year, about half a million people develop a drug-resistant form of TB (DR-TB).

The vast majority of people with TB live in low- and middle-income countries, where access to tests and treatments for all diseases is often challenging. This lack of access means more than a third of all TB infections go unreported.

The problem is even more acute among those with drug-resistant forms of the disease. Since 2020, due in part to the impact of the COVID-19 pandemic on global TB control programs, the situation has been getting worse, not better. Less than 60% of DR-TB patients treated were cured in 2020.

Doctors reviewing a patient’s medication in a rural TB clinic in South Sudan.

Antimicrobial awareness

World Antimicrobial Awareness Week 2021 is drawing increased attention to the global health, financial, and security impacts of growing resistance to drugs the world has long relied on to treat many infectious diseases.

This is therefore a timely moment to examine the threats, progress, and needs relating to drug-resistant tuberculosis (TB) – the single largest cause of death from resistant infections.

The inadequacy of tools to effectively diagnose and treat DR-TB has led to this diagnosis and treatment gap, but recent advances could turn the tide. However, we need to protect these advances long enough for them to have a meaningful impact on the fight against TB.

New drugs need to be used appropriately, matched against the bacterial strains that are susceptible to them. New diagnostics can confirm this match. But using the new drugs to treat the wrong strains will inevitably lead to more infections becoming resistant to the new drugs, and the overall threat of drug resistance will continue to increase.

In the fight against DR-TB, time is of the essence. Slower diagnosis and treatment times increase the risk, giving the bacteria more time to become resistant. Increasing access to rapid testing and shorter drug regimens for DR-TB allows for patients to be tested and treated faster, increasing the prospects that patients would complete treatment.

Gold-standard molecular diagnosis can now be made when patients meet with their doctors. A new testing platform from an Indian manufacturer—endorsed by the World Health Organization in 2020 and available today in more than 50 countries—can provide both the initial diagnosis of TB and the detection of rifampicin resistance.

Next-generation tests for multi-drug resistant and extensively drug-resistant forms of the disease approved earlier this year mean clinicians can now generate rapid and accurate drug-resistance profiles, allowing doctors to start patients on better, targeted treatments. A pipeline of new, affordable point-of-care tools for both TB infection as well as drug resistance testing could be made possible with only a small fraction of the investments currently devoted to COVID-19.

Advances in treatment

Site initiation and training for MolBio TrueNAT HCV assay multi-center performance evaluation at St. Paul Hospital, Addis Ababa, Ethiopia.

On the treatment front, therapy for DR-TB had long been characterized by extremely lengthy drug regimens rife with debilitating side effects, such as hearing loss and kidney failure.

Those suffering from highly drug-resistant disease were routinely subject to therapy lasting 18-months or longer, with poor cure rates despite up to 14,000 pills. The financial and human resource cost of administering such therapies has restricted patient access to these treatments in low-income settings.

Recent advances in therapy for highly drug-resistant TB include a six-month, three-drug regimen with a cure rate of approximately 90% and a significantly lower price tag. It is now being procured by more than 30 countries – a promising start to widespread adoption.

Testing and treating are inextricably linked as pillars of fighting AMR. The right diagnosis does not matter if the treatment is intolerable and ineffective. And the best possible treatment only works if it is administered to a patient who actually has the disease for which it is intended.

Crisis of neglect

TB and COVID-19 are both respiratory diseases, with patients often presenting with a cough. But one is bacterial, requiring several specific antibiotics, and the other viral, requiring a different set of therapeutics, the first of which is only now being presented to regulatory authorities.

The important point is that we must be able to distinguish between different causes of the same symptoms and do it quickly. “Just in case” – or uninformed – antimicrobial use for a range of diseases in the absence of a definitive diagnosis drives resistance and puts our hard-won antibiotics at risk.

The ongoing battle against DR-TB is being waged by researchers and clinicians whose labs are starved for resources, and health systems striving to overcome a crisis enabled by decades of neglecting TB. In 2020, the death toll from TB globally was second only to COVID-19 among infectious diseases. And for TB, this death toll has happened for decades if not centuries and, without action, will continue unabated.

AMR has long been considered in global health circles as a silent threat, lacking urgency, resources, and focus. Yet DR-TB is a potent reminder that AMR is quickly getting louder and will become catastrophic if inaction continues.

As we shine a light this week on AMR, it’s important to remember a fact clearly illustrated by the COVID-19 pandemic: tackling a global health threat is a choice. It’s not science, but financial commitments and political will that are the greatest barriers to overcoming deadly infectious diseases.

Mel Spigelman
Bill Rodriguez
Mel Spigelman, MD, is the president and CEO of TB Alliance, a product development partnership dedicated to discovering and delivering better and faster TB cures. 
Bill Rodriguez, MD, is Chief Executive Officer of FIND, the global alliance for diagnostics. He has extensive experience serving as advisor to the World Health Organization and national governments on global HIV, Tuberculosis, Ebola, and COVID-19.




Image Credits: Dato Koridze , WHO/John Rae Photography, Ryan Ruiz/ FIND.

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