XDR Becoming More Resistant: "We Will Run Out of Letters Soon"

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Last week, the Global Center released a new issue brief on drug-resistant TB to mark World TB Day. Included in the brief was this interview with Dr. Sarita Shah, who recently presented new research showing that strains of extensively drug-resistant TB (XDR-TB) in Tugela Ferry, South Africa, are becoming more resistant.

Tugela Ferry is ground zero for XDR, where doctors first described this deadly bug in 2005. Soon, 53 patients were diagnosed with XDR-TB; 52 of those patients died within an average of 16 days after they sought medical care. Since those first cases emerged, over 500 patients in Tugela Ferry have been diagnosed with XDR-TB, and cases of this deadly infection have been reported in 58 countries. And because of inadequate treatment, XDR-TB strains have developed resistance to an even greater number of drugs than before. In this Q&A, Dr. Shah, an assistant professor of medicine and of epidemiology and population health at Albert Einstein College of Medicine, describes a global health system that essentially guarantees the continued spread of multidrug-resistant TB (MDR-TB) and XDR-TB and talks about innovative efforts to transform the treatment of drug-resistant TB.

Q: You presented new research at the Union World Conference on Lung Health in 2009 showing that XDR has become more resistant. Why and how is this happening?

A: In July 2005, most of the XDR we analyzed in Tugela Ferry was resistant to four to five drugs. By 2009, 100% of patients in our study had XDR that was resistant to at least 6 drugs—and most to 8 drugs. This is a very worrying trend. But it’s not a surprise that drug resistance is going to increase if we have weak TB programs, not enough support, and not enough attention to this critical issue. This is happening because in many places, MDR is being treated in a completely unsupported, chaotic way. That treatment fails, and then we get XDR. And it’s not surprising that if we don’t treat XDR properly, it’s going to get ever more resistant. We will run out of letters soon, and we’ll be at the end of the road, with no more medicines available.

Q: Can you talk about the lineage of XDR and how it was initially passed along?

A: XDR has been around for a very long time. It was present in South Africa as early as 2001. Now that people are looking for it, we’re finding it everywhere. It isn’t a person spreading it around. It’s the conditions that create XDR, and those are everywhere—weak public health infrastructure and inadequate patient support for completing treatment, plus HIV/AIDS.

Q: Can you describe what’s happening on the ground now in KwaZulu-Natal Province, where you and your colleagues do much of your work on drug-resistant TB?

A: What happens in South Africa—and in many other countries around the world—is there’s a centralized, specialty hospital that treats all patients with MDR-TB, because the drugs used for treatment are complicated, expensive and specialized. So, it is felt that treatment should be by specialists who can use the drugs correctly and monitor for side effects appropriately. In KwaZulu-Natal, this hospital used to be able to admit all MDR patients for six months, during which patients are assured to take their medicines every single day. And then for the remaining year and a half of MDR treatment, the patients are supposed to come back every month for a check-up and more medicines. You can probably imagine that not everyone comes back. They live far away. They’re probably feeling better. They can’t afford to miss a day of work. So what happens? In South Africa, we had an MDR default rate of 15–20% percent, so you’re at XDR.

Starting about four years ago, that referral hospital became completely overwhelmed. They have 160 beds, and we diagnose over 2,500 MDR cases in our province alone per year, so you can see how that math doesn’t work. Since the central hospital couldn’t admit everyone anymore, there were long waiting lists to get into the hospital, which is the only way to get the MDR medicines. Half of the diagnosed cases might die before being admitted. The same thing happens in other places as well—or worse, no MDR treatment is available in the country at all—so it’s important to realize South Africa isn’t unique in this sense. The issue of getting MDR patients access to good drugs in a timely way is a major global effort led by the Green Light Committee.

But let’s say a patient manages to get in to the MDR hospital. The doctors would try to give him or her medicines, but they might discharge the patient after 3 or 4 months because they have to face the daily reality of the long waiting lists of patients who are, literally, dying while waiting to get access to the medicines. So, patients are discharged early—with all the best intentions of trying to get more people into care—but, this is the way you get more resistance and also transmit disease to others.

Q: What’s the fix for this kind of situation that guarantees failed treatment, more transmission, and greater resistance?    

A: We’ve been able to make significant progress in the last couple of years. In KwaZulu-Natal, MDR treatment has been decentralized to 4 hospitals around the province. So there are more inpatient beds, and the patients don’t have to wait nearly as long, on the order of about 1 or 2 weeks. With increased intake for MDR treatment, they have a better chance at surviving and they don’t spread disease. The other thing we’ve done in KwaZulu-Natal is, in the district where Tugela Ferry is located, we’re treating MDR patients in their community, at their homes. We’re never going to get to the 2,500 beds—we have about 500 right now—nor do I think we should be aiming for that. We need a more patient-centered approach that will help them complete treatment successfully and be cured of MDR. So moving to a community-based model of treatment is key. We provide education on MDR and HIV for the patients and their families, so they know what it is they have, how it is spread, and what the treatment involves. We send nurses to their homes daily to give the injections for the first 6 months. We’re in contact with the patients every day, at their homes, so they don’t default from treatment.

The other major concern with this approach is placing others in the home at risk, but they have already been exposed, so we’re not increasing their risk of transmission. We take infection control very seriously and emphasize masks for our nurses, giving injections outside in the open air, and keeping windows and doors open. But, again, providing treatment—in the hospital or the community—has to be done in an organized, well supported and monitored way or we will create more resistance.

Q: Some experts fear we could reach a “tipping point” in which the majority of new TB cases are drug resistant, rather than standard TB that’s easily treated with available drugs. Do you agree with that?

A: Drug-susceptible TB still accounts for the vast majority of new TB cases. It’s curable, diagnosable, and preventable. But, we’re losing the war against TB right now for many reasons, most of which have to do with weak public health infrastructure, but also political will. MDR and XDR are certainly going to increase if we don’t do something now to prevent creating more of these strains. It starts with susceptible TB; we’ve got to diagnosis it faster, so infected patients will stop spreading the disease. And we need to treat them faster and make sure they complete treatment, so they will not develop MDR. We also have to diagnose MDR faster— which is more complicated, but is definitely doable—and we’ve got to treat it properly. With proper treatment for MDR, you generally become uninfectious within two to four weeks, so we can do this. It’s a long treatment, but it can be done and it is being done in some parts of the world very effectively. It’s a matter of infrastructure, support, political commitment, and better diagnostic tools.

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