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PLOS BLOGS Speaking of Medicine

Combatting MDR-TB: Bringing a Knife to a Gunfight

Animesh Sinha, a physician with Médecins Sans Frontières, describes how bedaquiline and delamanid changed the game for treating multidrug-resistant tuberculosis and stresses the importance of making these drugs widely available.

I saw my first patient with extensive drug-resistant tuberculosis (XDR-TB) in early 2013, at a TB clinic run by Médecins Sans Frontières (MSF) in Chechnya. My first thought was that he had only a one-in-four chance of being cured by the drugs we had available. It was difficult to explain to him why, in this day and age, we didn’t have better treatment for one of the world’s leading infectious disease killers.

Now, since the approval of bedaquiline and delamanid (two effective new drugs), we do—although very few people who could benefit have access to them. But I dare to hope, since the World Health Organisation (WHO) recently prioritised the use of bedaquiline and will soon re-assess delamanid. I dare to hope we can build on the latest calls to action from September’s first-ever United Nations General Assembly High-Level Meeting on TB and this week’s 49th Union World Conference on Lung Health, which urge more effective, coordinated global action against TB based on respect for individual human rights.

A key priority is to reverse our failures against multidrug-resistant TB (MDR-TB): worldwide only an estimated 25% of people who contracted MDR-TB in 2016 were diagnosed and notified—and of those, just over 50% were successfully treated. In other words, 7 out of 8 MDR-TB patients did not receive the treatment they needed. When the odds are stacked 7:1 in favour of the disease, can we call our feeble effort a full fight? MDR-TB has unleashed brutal suffering on millions of people, while we struggle to respond using ill-adapted diagnostic tools and harsh, ineffective regimens.

I saw this first hand during my early days at the MSF TB project in Grozny, the capital city of Chechnya (Russian Federation). Our project supported the Republican Tuberculosis Dispensary in managing MDR-TB patients from all over Chechnya, where the rate of new MDR-TB cases at that time was among the country’s highest. I had a decade of experience treating patients with drug-sensitive TB, but my theoretical knowledge of how to manage MDR-TB was no match for the harsh realities on ground. It was horribly frustrating when there was little I could do to help patients with the painful, often permanently debilitating side effects of the available drugs—from nausea, joint pain and psychosis to permanent hearing loss. Some patients found the treatment so difficult that it was easier to accept death than to take those nauseating pills and painful injections for up to two years, for what seemed like only a glimmer of hope for TB-free survival.

Ambulatory treatment in the remote village of Kenkhi in the mountainous Sharoy district of Chechnya. A Local helper visits Sapikhat, 53, an XDR TB patient, to deliver her daily medicine. Photo by Lana Abramova

Things changed in 2014 when our project gained access to bedaquiline and delamanid—the first novel TB drugs in 50 years. We immediately started switching MDR-TB patients to new combinations containing one or both drugs, raising hopes especially among those who had not responded to the older drugs. What’s more, delamanid opened up options to treat children and adolescents, including improved regimens for children with extensively drug-resistant TB (XDR-TB).

One of my patients was a young woman who had stopped treatment after several courses of different MDR-TB regimens which hadn’t worked and only made her feel sicker. She then tried to leave the country for Europe, where the new drugs were available, but could not get a visa. Once our project began using the new drugs, outreach workers traced her and gave her this news. At that point these drugs were probably her last hope of survival. She started a new regimen in December 2014 and within 4 months achieved culture conversion (i.e., her sputum tested negative for TB), a major milestone en route to being cured. At two years, this “incurable” patient was completely cured.

In the roughly 2-1/2 years MSF ran the project after introducing bedaquiline and delamanid, we treated 156 patients with combinations containing one or both drugs. Some were sick with MDR/XDR-TB for the first time, while others had previously undergone unsuccessful treatments or had relapsed. In most cases, I saw patients respond well and tolerate treatment better than before. As a physician, it was extremely empowering to finally fight back more effectively against this epidemic.

The new WHO recommendations to prioritise bedaquiline and to re-assess delamanid pending results from ongoing studies raise high hopes. These drugs are long-awaited reinforcements in a failing battle and should be made available to every physician managing MDR-TB patients; countries and global health actors must meet this challenge. True, the new drugs are not magic bullets: treatment is still very long and often has side effects (though milder), and optimal combinations with other drugs are not yet well-understood. But it is totally unacceptable to engage in debating how many angels can dance on the head of a pin while lives are lost for want of these new tools. Without expeditious implementation of the new WHO recommendations, we will be reneging on our commitment to put individual human rights at the centre of the TB response and instead will continue our history of bringing a knife to a gunfight.

Animesh Sinha is a medical doctor working with Médecins Sans Frontières on tuberculosis. He is currently in Minsk supporting clinical studies aimed at developing much shorter regimens for MDR-TB treatment that include bedaquiline and other new drugs.

 

 

Feature image: The author and members of MSF’s TB team check medical records of patients in the XDR-TB ward of the Republican TB Dispensary in Grozny. Photo by Lana Abramova

Photo 2: Ambulatory treatment in the remote village of Kenkhi, in Chechnya’s mountainous Sharoy district. A local helper visits an XDR-TB patient to deliver her daily medicine. Photo by Lana Abramova

 

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